Novel antibodies that bind to antigenic polypeptides, nucleic acids encoding the antigens, and methods of use

Abstract

Disclosed herein are nucleic acid sequences that encode polypeptides. Also disclosed are antibodies, which immunospecifically-bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the aforementioned polypeptide, polynucleotide, or antibody. 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, polypeptides, or antibodies, or fragments thereof.

Description

FIELD OF THE INVENTION

[0002] The present invention relates to novel antibodies that bind immunospecifically to antigenic polypeptides, wherein the polypeptides have characteristic properties related to biochemical or physiological responses in a cell, a tissue, an organ or an organism. The novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use of the antibodies encompass procedures for diagnostic and prognostic assay of the polypeptides, 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 elevated or excessive synthesis and secretion of protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by elevated or excessive levels of a 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 nucleic acid sequences encoding novel polypeptides. The novel nucleic acids and polypeptides are referred to herein as NOVX, or NOV1, NOV2, NOV3, etc., nucleic acids and polypeptides. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid or polypeptide sequences.

[0010] In one aspect, the invention provides an isolated polypeptide comprising a mature form of a NOVX amino acid. The polypeptide can be, for example, a NOVX amino acid sequence or a variant of a NOVX amino acid sequence, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed. The invention also includes fragments of any of NOVX polypeptides. In another aspect, the invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof.

[0011] Also included in the invention is a NOVX polypeptide that is a naturally occurring variant of a NOVX sequence. In one embodiment, the variant includes an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a NOVX nucleic acid sequence. In another embodiment, the NOVX polypeptide is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution.

[0012] In another aspect, invention provides a method for determining the presence or amount of the NOVX polypeptide in a sample by providing a sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the NOVX polypeptide, thereby determining the presence or amount of the NOVX polypeptide in the sample.

[0013] In yet another aspect, the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide in a mammalian subject by measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in the sample of the first step to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease. 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.

[0014] In another aspect, the invention includes pharmaceutical compositions that include therapeutically- or prophylactically-effective amounts of a therapeutic and a pharmaceutically-acceptable carrier. The therapeutic can be, e.g., a NOVX nucleic acid, a NOVX polypeptide, or an antibody specific for a NOVX polypeptide. In a further aspect, the invention includes, in one or more containers, a therapeutically- or prophylactically-effective amount of this pharmaceutical composition.

[0015] In still another aspect, the invention provides the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease that is associated with a NOVX polypeptide.

[0016] In a further aspect, the invention provides a method for modulating the activity of a NOVX polypeptide by contacting a cell sample expressing the NOVX polypeptide with antibody that binds the NOVX polypeptide in an amount sufficient to modulate the activity of the polypeptide.

[0017] The invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof. In a preferred embodiment, the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant. In another embodiment, the nucleic acid encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence. In one embodiment, the NOVX nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 73, or a complement of the nucleotide sequence. In one embodiment, the invention provides a nucleic acid molecule wherein the nucleic acid includes the nucleotide sequence of a naturally occurring allelic nucleic acid variant.

[0018] Also included in the invention is a vector containing one or more of the nucleic acids described herein, and a cell containing the vectors or nucleic acids described herein. The invention is also directed to host cells transformed with a vector comprising any of the nucleic acid molecules described above.

[0019] In yet another aspect, the invention provides for a method for determining the presence or amount of a nucleic acid molecule in a sample by contacting a sample with a probe that binds a NOVX nucleic acid and determining the amount of the probe that is bound to the NOVX nucleic acid. For example the NOVX nucleic may be a marker for cell or tissue type such as a cell or tissue type that is cancerous.

[0020] In yet a further aspect, the invention provides a method for determining the presence of or predisposition to a disease associated with altered levels of a nucleic acid molecule in a first mammalian subject, wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

[0021] 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.

[0022] 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.

[0023] 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.

[0024] 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.

[0025] Other features and advantages of the invention will be apparent from the following detailed description and claims.

DETAILED DESCRIPTION OF THE INVENTION

[0026] The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compunds. 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 1 provides a summary of the NOVX nucleic acids and their encoded polypeptides.

TABLE 1
NOVX Polynucleotide and Polypeptide Sequences and
Corresponding SEQ ID Numbers
		SEQ ID
		NO
		(nucleic	SEQ ID NO
	Internal Identification	acid)	(polypeptide)	Homology
1a	CG100653-01	1	2	Cadherin Associated Protein-like
2a	CG100689-01	3	4	Leucine Rich Repeat-like
3a	CG100760-01	5	6	Leucine Rich Repeat-like
4a	CG100851-02	7	8	Leukocyte Surface Antigen
				CD53-like
5a	CG101068-01	9	10	Claudin-9-like
6a	CG101231-01	11	12	Integral Membrane Protein Isoform
				2-like
6b	CG101231-02	13	14	Integral Membrane Protein Isoform
				2-like
7a	CG101362-01	15	16	Prion Protein-like
8a	CG101458-01	17	18	Von Willebrand Domain
				Containing Protein-like
9a	CG101475-01	19	20	Plasma Membrane Protein-like
9b	CG101475-02	21	22	Plasma Membrane Protein-like
10a	CG101772-01	23	24	XAGE-like
11a	CG102532-01	25	26	Emerin-like
12a	CG102575-01	27	28	ATPase-like
12b	CG102575-02	29	30	ATPase-like
13a	CG102615-01	31	32	Mat8 (Mammary Tumor 8 kDa)
				Protein-like
13b	CG102615-04	33	34	Mat8 (Mammary Tumor 8 kDa)
				Protein-like
14a	CG102646-01	35	36	High Affinity Proline Permease-like
15a	CG102878-01	37	38	Transmembrane-like
15b	CG102878-02	39	40	Transmembrane-like
16a	CG103459-01	41	42	Peptide/Histidine Transporter-like
17a	CG104210-01	43	44	Type III Membrane Protein-like
17b	CG104210-02	45	46	Type III Membrane Protein-like
17c	272249075	47	48	Type III Membrane Protein-like
18a	CG104251-01	49	50	Type III Membrane Protein-like
19a	CG104934-01	51	52	Phospholipid-Transporting ATPase
				IH-like
20a	CG105463-01	53	54	Meningioma-Expressed Antigen
				6/11 (MEA6) (MEA11)-like
20b	CG105463-02	55	56	Meningioma-Expressed Antigen
				6/11 (MEA6) (MEA11)-like
21a	CG105491-01	57	58	Serine Protease-like
22a	CG105954-01	59	60	Neurofascin Precursor-like
23a	CG105963-01	61	62	Cadherin-like
24a	CG105973-01	63	64	Integrin Alpha 8-like
24b	CG105973-02	65	66	Integrin Alpha 8-like
25a	CG106915-01	67	68	Nogo Receptor Isoform-1-like
26a	CG106924-01	69	70	Nogo Receptor Isoform-2-like
26b	210062144	71	72	Nogo Receptor Isoform-2-like
27a	CG106942-01	73	74	NRAMP-like Membrane Protein
28a	CG107513-01	75	76	Syntaxin Domain Containing
				Protein-like
29a	CG107533-02	77	78	Tumor Necrosis Factor-like
30a	CG107562-01	79	80	Leucine-Rich Repeat Type III
				Transmembrane-like
30b	CG107562-02	81	82	Leucine-Rich Repeat Type III
				Transmembrane-like
30c	210086373	83	84	Leucine-Rich Repeat Type III
				Transmembrane-like
30d	210086403	85	86	Leucine-Rich Repeat Type III
				Transmembrane-like
30e	210086422	87	88	Leucine-Rich Repeat Type III
				Transmembrane-like
31a	CG108184-01	89	90	Transmembrane Protein Tm7-like
31b	CG108184-02	91	92	Transmembrane Protein Tm7-like
31c	CG108184-03	93	94	Transmembrane Protein Tm7-like
32a	CG108238-01	95	96	Sialic Acid Binding
				Immunoglobulin-like
33a	CG108695-01	97	98	OB binding protein (SIGLEC)-like
34a	CG109505-01	99	100	Aldehyde Dehydrogenase-like
35a	CG109742-01	101	102	Latent Transforming Growth Factor
				Beta Binding Protein 3-like
35b	207639410	103	104	Latent Transforming Growth Factor
				Beta Binding Protein 3-like
35c	207639427	105	106	Latent Transforming Growth Factor
				Beta Binding Protein 3-like
35d	207639438	107	108	Latent Transforming Growth Factor
				Beta Binding Protein 3-like
35e	207639448	109	110	Latent Transforming Growth Factor
				Beta Binding Protein 3-like
36a	CG109844-01	111	112	C4B-Binding Protein-like
37a	CG110014-02	113	114	Colon Carcinoma kinase 4-like
37b	CG110014-03	115	116	Colon Carcinoma kinase 4-like
37c	CG110014-04	117	118	Colon Carcinoma kinase 4-like
38a	CG110187-01	119	120	Alpha C1-like Protocadherin
38b	CG110187-03	121	122	Alpha C1-like Protocadherin
39a	CG110205-01	123	124	Disintegrin-like/Metalloprotease
				(Reprolysin Type) with
				Thrombospondin Type I Motif-like
39b	CG110205-02	125	126	Disintegrin-like/Metalloprotease
				(Reprolysin Type) with
				Thrombospondin Type I Motif-like
39c	207756942	127	128	Disintegrin-like/Metalloprotease
				(Reprolysin Type) with
				Thrombospondin Type I Motif-like
39d	207756946	129	130	Disintegrin-like/Metalloprotease
				(Reprolysin Type) with
				Thrombospondin Type I Motif-like
39e	207756950	131	132	Disintegrin-like/Metalloprotease
				(Reprolysin Type) with
				Thrombospondin Type I Motif-like
39f	207756966	133	134	Disintegrin-like/Metalloprotease
				(Reprolysin Type) with
				Thrombospondin Type I Motif-like
40a	CG110242-01	135	136	Ebnerin-like
40b	207728344	137	138	Ebnerin-like
40c	207728348	139	140	Ebnerin-like
40d	207728354	141	142	Ebnerin-like
40e	207728365	143	144	Ebnerin-like
41a	CG99598-01	145	146	Endosomal Glycoprotein
				Precursor-like

[0027] Table 1 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 1 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 1.

[0028] 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.

[0029] Consistent with other known members of the family of proteins, identified in column 5 of Table 1, 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.

[0030] 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 1.

[0031] 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.

[0032] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.

[0033] NOVX Clones

[0034] 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.

[0035] 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.

[0036] The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as research tools. 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.

[0037] 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 73; (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 73, 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 73; (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 73 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).

[0038] 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 73; (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 73 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 73; (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 73, 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 73 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.

[0039] 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 73; (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 73 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 73; 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 73 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.

[0040] NOVX Nucleic Acids and Polypeptides

[0041] 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 mRNA's) 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.

[0042] 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, again by way of nonlimiting example, as a result of one or more naturally occurring processing steps as they may take place within the cell, or host cell, in which the gene product arises. Examples of such processing steps leading to a “mature” form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+1 to residue N remaining. Further as used herein, a “mature” form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, 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.

[0043] The term “probes”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), 100 nt, or as many as approximately, e.g., 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single- or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.

[0044] The term “isolated” nucleic acid molecule, as utilized herein, is one, which is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5′- and 3′-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.). Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material or culture medium when produced by recombinant techniques, or of chemical precursors or other chemicals when chemically synthesized.

[0045] 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 1-73, or a complement of this aforementioned nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO:2n−1, wherein n is an integer between 1-73, 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.)

[0046] A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template and appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to NOVX nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.

[0047] As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues, which oligonucleotide has a sufficient number of nucleotide bases to be used in a PCR reaction. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise portions of a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NO:2n−1, wherein n is an integer between 1-73, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.

[0048] In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence SEQ ID NO:2n−1, wherein n is an integer between 1-73, 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 1-73, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1-73, that it can hydrogen bond with little or no mismatches to the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1-73, thereby forming a stable duplex.

[0049] 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.

[0050] Fragments provided herein are defined as sequences of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, respectively, and are at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice. Derivatives are nucleic acid sequences or amino acid sequences formed from the native compounds either directly or by modification or partial substitution. Analogs are nucleic acid sequences or amino acid sequences that have a structure similar to, but not identical to, the native compound but differs from it in respect to certain components or side chains. Analogs may be synthetic or from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. Homologs are nucleic acid sequences or amino acid sequences of a particular gene that are derived from different species.

[0051] 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.

[0052] Derivatives and analogs may be full length or other than full length, if the derivative or analog contains a modified nucleic acid or amino acid, as described below. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the aforementioned proteins under stringent, moderately stringent, or low stringent conditions. See e.g. Ausubel, et al., Current Protocols in Molecular Biology, John Wiley & Sons, New York, N.Y., 1993, and below.

[0053] A “homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences encode those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for 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 1-73, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.

[0054] 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.

[0055] 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 1-73; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1-73; or of a naturally occurring mutant of SEQ ID NO:2n−1, wherein n is an integer between 1-73.

[0056] Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In various embodiments, the probe further comprises a label group attached thereto, e.g. the label group can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express 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.

[0057] “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 1-73, 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.

[0058] NOVX Nucleic Acid and Polypeptide Variants

[0059] 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 1-73, 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 1-73. 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 1-73.

[0060] In addition to the human NOVX nucleotide sequences of SEQ ID NO:2n−1, wherein n is an integer between 1-73, 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.

[0061] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from any one of the human SEQ ID NO:2n−1, wherein n is an integer between 1-73, 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.

[0062] 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 1-73. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences at least 60% homologous to each other typically remain hybridized to each other.

[0063] 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.

[0064] 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.

[0065] Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6×SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65° C., followed by one or more washes in 0.2×SSC, 0.01% BSA at 50° C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to any one of the sequences of SEQ ID NO:2n−1, wherein n is an integer between 1-73, 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).

[0066] 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 1-73, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6×SSC, 5×Reinhardt's solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55° C., followed by one or more washes in 1×SSC, 0.1% SDS at 37° C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, Current Protocols in Molecular Biology, John Wiley & Sons, NY, and Krieger, 1990; Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY.

[0067] 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 1-73, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/volt) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, Current Protocols in Molecular Biology, John Wiley & Sons, NY, and Kriegler, 1990, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY; Shilo and Weinberg, 1981. Proc Natl Acad Sci USA 78:6789-6792.

[0068] Conservative Mutations

[0069] 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 1-73, thereby leading to changes in the amino acid sequences of the encoded NOVX proteins, without altering the functional ability of said NOVX proteins. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence of SEQ ID NO:2n, wherein n is an integer between 1-73. 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 particularly non-amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.

[0070] 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 any one of SEQ ID NO:2n−1, wherein n is an integer between 1-73, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 45% homologous to the amino acid sequences of SEQ ID NO:2n, wherein n is an integer between 1-73. 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 1-73; more preferably at least about 70% homologous to SEQ ID NO:2n, wherein n is an integer between 1-73; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1-73; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1-73; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1-73.

[0071] An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO:2n, wherein n is an integer between 1-73, 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 1-73, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

[0072] Mutations can be introduced into any of SEQ ID NO:2n−1, wherein n is an integer between 1-73, 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 any one of SEQ ID NO:2n−1, wherein n is an integer between 1-73, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

[0073] 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.

[0074] 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).

[0075] 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).

[0076] Antisense Nucleic Acids

[0077] 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 1-73, 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 1-73, or antisense nucleic acids complementary to a NOVX nucleic acid sequence of SEQ ID NO:2n−1, wherein n is an integer between 1-73, are additionally provided.

[0078] In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding a NOVX protein. The term “coding region” refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid molecule is antisense to a “noncoding region” of the coding strand of a nucleotide sequence encoding the NOVX protein. The term “noncoding region” refers to 5′ and 3′ sequences which flank the coding region that are not translated into amino acids (i.e., also referred to as 5′ and 3′ untranslated regions).

[0079] 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).

[0080] Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been 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).

[0081] The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.

[0082] 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.

[0083] Ribozymes and PNA Moieties

[0084] 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.

[0085] 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., any one of SEQ ID NO:2n−1, wherein n is an integer between 1-73). 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.

[0086] 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.

[0087] 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.

[0088] PNAs of NOVX can be used in therapeutic and diagnostic applications. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, e.g., inducing transcription or translation arrest or inhibiting replication. PNAs of NOVX can also be used, for example, in the analysis of single base pair mutations in a gene (e.g., PNA directed PCR clamping; as artificial restriction enzymes when used in combination with other enzymes, e.g., S1 nucleases (See, Hyrup, et al., 1996.supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al., 1996, supra; Perry-O'Keefe, et al., 1996. supra).

[0089] 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.

[0090] 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.

[0091] NOVX Polypeptides

[0092] 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 1-73. 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 1-73, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

[0093] 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.

[0094] 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.

[0095] 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.

[0096] 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.

[0097] 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 1-73) 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.

[0098] 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.

[0099] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1-73. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1-73, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1-73, 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 1-73, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1-73.

[0100] Determining Homology between Two or More Sequences

[0101] 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”).

[0102] 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 1-73.

[0103] 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.

[0104] Chimeric and Fusion Proteins

[0105] 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 1-73, 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.

[0106] 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.

[0107] 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.

[0108] 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.

[0109] 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.

[0110] NOVX Agonists and Antagonists

[0111] 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.

[0112] 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.

[0113] Polypeptide Libraries

[0114] In addition, libraries of fragments of the NOVX protein coding sequences can be used to generate a variegated population of NOVX fragments for screening and subsequent selection of variants of a NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a NOVX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S1 nuclease, and ligating the resulting fragment library into an expression vector. By this method, expression libraries can be derived which encodes N-terminal and internal fragments of various sizes of the NOVX proteins.

[0115] 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.

[0116] NOVX Antibodies

[0117] 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.

[0118] 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 1-73, 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.

[0119] 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, 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.

[0120] 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 polyppeptide or a fragment thereof comprises at least one antigenic epitope. An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (KD) is ≦1 μM, preferably ≦100 nM, more preferably ≦10 nM, and most preferably ≦100 pM to about 1 pM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art.

[0121] 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.

[0122] 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.

[0123] Polyclonal Antibodies

[0124] 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).

[0125] 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).

[0126] Monoclonal Antibodies

[0127] 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.

[0128] 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.

[0129] 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.

[0130] 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).

[0131] 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.

[0132] 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.

[0133] The monoclonal antibodies secreted by the subdlones 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.

[0134] 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.

[0135] Humanized Antibodies

[0136] 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)).

[0137] Human Antibodies

[0138] 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).

[0139] 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)).

[0140] Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal's endogenous antibodies in response to challenge by an antigen. (See PCT publication WO94/02602). The endogenous genes encoding the heavy and light immunoglobulin chains in the nonhuman host have been incapacitated, and active loci encoding human heavy and light chain immunoglobulins are inserted into the host's genome. The human genes are incorporated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications. The preferred embodiment of such a nonhuman animal is a mouse, and is termed the Xenomouse™ as disclosed in PCT publications WO 96/33735 and WO 96/34096. This animal produces B cells which secrete fully human immunoglobulins. The antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies. Additionally, the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules.

[0141] 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.

[0142] 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.

[0143] 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.

[0144] Fab Fragments and Single Chain Antibodies

[0145] 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.

[0146] Bispecific Antibodies

[0147] 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.

[0148] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published May 13, 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).

[0149] 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).

[0150] 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.

[0151] 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.

[0152] 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.

[0153] 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).

[0154] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[0155] 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).

[0156] Heteroconjugate Antibodies

[0157] 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.

[0158] Effector Function Engineering

[0159] 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).

[0160] Immunoconjugates

[0161] 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).

[0162] 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.

[0163] 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.

[0164] 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.

[0165] Immunoliposomes

[0166] 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.

[0167] 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).

[0168] Diagnostic Applications of Antibodies Directed against the Proteins of the Invention

[0169] Antibodies directed against a protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of the protein (e.g., for use in measuring levels of the protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies against the proteins, or derivatives, fragments, analogs or homologs thereof, that contain the antigen binding domain, are utilized as pharmacologically-active compounds (see below).

[0170] An antibody specific for a protein of the invention can be used to isolate the protein by standard techniques, such as immunoaffinity chromatography or immunoprecipitation. Such an antibody can facilitate the purification of the natural protein antigen from cells and of recombinantly produced antigen expressed in host cells. Moreover, such an antibody can be used to detect the antigenic protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic protein. Antibodies directed against the protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 35S or 3H.

[0171] Antibody Therapeutics

[0172] 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.

[0173] 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.

[0174] 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.

[0175] Pharmaceutical Compositions of Antibodies

[0176] 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.

[0177] 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.

[0178] 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.

[0179] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

[0180] 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 γethyl-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.

[0181] ELISA Assay

[0182] An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab)2) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term “biological sample”, therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in “ELISA: Theory and Practice: Methods in Molecular Biology”, Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, N.J., 1995; “Immunoassay”, E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, Calif., 1996; and “Practice and Thory of Enzyme Immunoassays”, P. Tijssen, Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-an analyte protein antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.

[0183] NOVX Recombinant Expression Vectors and Host Cells

[0184] 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.

[0185] 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).

[0186] 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.).

[0187] 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.

[0188] 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.

[0189] 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).

[0190] 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.

[0191] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSec1 (Baldari, et al., 1987. EMBO J. 6: 229-234), pMFa (Kurjan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al., 1987. Gene 54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).

[0192] 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).

[0193] 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.

[0194] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987. Genes Dev. 1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol. 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and immunoglobulins (Banerji, et al., 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985. Science 230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990. Science 249: 374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546).

[0195] 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.

[0196] 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.

[0197] 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.

[0198] 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.

[0199] 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).

[0200] A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (ie., 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.

[0201] Transgenic NOVX Animals

[0202] 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.

[0203] 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 1-73, 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.

[0204] 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 1-73), 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 1-73, 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).

[0205] 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.

[0206] 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.

[0207] 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.

[0208] Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al., 1997. Nature 385: 810-813. In brief, a cell (e.g., a somatic cell) from the transgenic animal can be isolated and induced to exit the growth cycle and enter G0 phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell (e.g., the somatic cell) is isolated.

[0209] Pharmaceutical Compositions

[0210] 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.

[0211] 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.

[0212] 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.

[0213] 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.

[0214] 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.

[0215] 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.

[0216] 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.

[0217] 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.

[0218] 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.

[0219] 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.

[0220] 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.

[0221] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0222] Screening and Detection Methods

[0223] 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.

[0224] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

[0225] Screening Assays

[0226] 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.

[0227] 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.

[0228] 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.

[0229] 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.

[0230] 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.).

[0231] 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.

[0232] 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.

[0233] 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.

[0234] 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.

[0235] 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.

[0236] 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.

[0237] The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether)n, N-dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate, 3-(3-cholamidopropyl)dimethylamminiol-1-propane sulfonate (CHAPS), or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane sulfonate (CHAPSO).

[0238] 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.

[0239] 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.

[0240] 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.

[0241] 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.

[0242] 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.

[0243] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

[0244] Detection Assays

[0245] 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.

[0246] Chromosome Mapping

[0247] 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 1-73, 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.

[0248] 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.

[0249] 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.

[0250] 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.

[0251] 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).

[0252] 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.

[0253] 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.

[0254] 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.

[0255] Tissue Typing

[0256] 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).

[0257] 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.

[0258] 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).

[0259] 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 1-73, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

[0260] Predictive Medicine

[0261] 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.

[0262] 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.)

[0263] 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.

[0264] These and other agents are described in further detail in the following sections.

[0265] Diagnostic Assays

[0266] 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 1-73, 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.

[0267] 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.

[0268] 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.

[0269] 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.

[0270] 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.

[0271] Prognostic Assays

[0272] 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.

[0273] 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).

[0274] 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.

[0275] 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.

[0276] Alternative amplification methods include: self sustained sequence replication (see, Guatelli, et al., 1990. Proc. Natl. Acad. Sci. USA 87: 1874-1878), transcriptional amplification system (see, Kwoh, et al., 1989. Proc. Natl. Acad. Sci. USA 86: 1173-1177); Qβ Replicase (see, Lizardi, et al, 1988. BioTechnology 6: 1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.

[0277] 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.

[0278] 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.

[0279] 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).

[0280] Other methods for detecting mutations in the NOVX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e.g., Myers, et al., 1985. Science 230: 1242. In general, the art technique of “mismatch cleavage” starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type NOVX sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S1 nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e.g., Cotton, et al., 1988. Proc. Natl. Acad. Sci. USA 85: 4397; Saleeba, et al., 1992. Methods Enzymol. 217: 286-295. In an embodiment, the control DNA or RNA can be labeled for detection.

[0281] 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.

[0282] 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.

[0283] 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.

[0284] 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.

[0285] 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.

[0286] 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.

[0287] 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.

[0288] Pharmacogenomics

[0289] 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 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.) 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.

[0290] 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.

[0291] 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.

[0292] 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.

[0293] Monitoring of Effects During Clinical Trials

[0294] 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.

[0295] 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.

[0296] 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.

[0297] Methods of Treatment

[0298] The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant NOVX expression or activity. The disorders include cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, transplantation, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn's disease; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, and other diseases, disorders and conditions of the like.

[0299] These methods of treatment will be discussed more fully, below.

[0300] Disease and Disorders

[0301] 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.

[0302] 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.

[0303] 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).

[0304] Prophylactic Methods

[0305] 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.

[0306] Therapeutic Methods

[0307] Another aspect of the invention pertains to methods of modulating NOVX expression or activity for therapeutic purposes. The modulatory method of the invention involves contacting a cell with an agent that modulates one or more of the activities of NOVX protein activity associated with the cell. An agent that modulates NOVX protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring cognate ligand of a NOVX protein, a peptide, a NOVX peptidomimetic, or other small molecule. In one embodiment, the agent stimulates one or more NOVX protein activity. Examples of such stimulatory agents include active NOVX protein and a nucleic acid molecule encoding NOVX that has been introduced into the cell. In another embodiment, the agent inhibits one or more NOVX protein activity. Examples of such inhibitory agents include antisense NOVX nucleic acid molecules and anti-NOVX antibodies. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e.g., by administering the agent to a subject). As such, the invention provides methods of treating an individual afflicted with a disease or disorder characterized by aberrant expression or activity of a NOVX protein or nucleic acid molecule. In one embodiment, the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e.g., up-regulates or down-regulates) NOVX expression or activity. In another embodiment, the method involves administering a NOVX protein or nucleic acid molecule as therapy to compensate for reduced or aberrant NOVX expression or activity.

[0308] Stimulation of NOVX activity is desirable in situations in which NOVX is abnormally downregulated and/or in which increased NOVX activity has 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).

[0309] Determination of the Biological Effect of the Therapeutic

[0310] 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.

[0311] 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.

[0312] Prophylactic and Therapeutic Uses of the Compositions of the Invention

[0313] The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders including, but not limited to: metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers.

[0314] As an example, a cDNA encoding the NOVX protein of the invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof. By way of non-limiting example, the compositions of the invention will have efficacy for treatment of patients suffering from: metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias.

[0315] 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.

EXAMPLES

Example A: Polynucleotide and Polypeptide Sequences, and Homology Data

Example 1

[0316] The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1A.

TABLE 1A
NOV1 Sequence Analysis
	SEQ ID NO:1	3430 bp
NOV1a,	GGGCTGCAGGAATTCCCCCACAGAGGGAGCATGACTTCGGCAACTTCACCTATCATTC
CG100653-01
DNA Sequence	TGAAATGGGACCCCAAAAGTTTGGAAATCCGGACGCTAACAGTGGAAAGGCTGTTGGA
	GCCACTTGTTACACAGGTGACTACACTTGTCAACACAAGCAACAAAGGCCCATCTGGT
	AAAAAGAAAGGGAGGTCAAAGAAAGCCCATGTACTAGCTGCCTCTGTAGAGCAAGCCA
	CTCAGAATTTCCTGGAAAAGGGTGAACAGATCGCTAAGGAGAGTCAAGATCTCAAAGA
	AGAGTTGGTGGCTGCTGTAGAGGATGTGCGCAAACAAGGTGAGACGATGCGGATCGCC
	TCCTCCGAGTTTGCAGATGACCCTTGCTCGTCGGTAAAGCGCGGCACCATGGTACGGG
	CGGCAAGGGCTTTGCTCTCCGCGGTGACACGCTTACTCATCCTGGCGGACATGGCAGA
	TGTCATGAGACTTTTATCCCATCTGAAAATTGTGGAAGAGGCCCTGGAAGCTGTCAAA
	AATGCTACAAATGAGCAAGACCTTGCAAACCGTTTTAAAGAGTTTGGGAAAAAGATGG
	TGAAACTTAACTATGTAGCAGCAAGAAGACAACAGGAGCTGAAGGATCCTCACTGTCG
	GGATGAGATGGCAGCCGCCCGAGGGGCTCTGAAGAAGAATGCCACAATGCTGTACACG
	GCCTCTCAAGCATTTCTCCGCCACCCAGATGTCGCCGCTACGAGAGCCAACCGAGATT
	ATGTGTTCAAACAAGTCCAGGAGGCCATCGCCGGCATCTCCAATGCTGCTCAAGCTAC
	CTCGCCCACTGACGAAGCCAAGGGCCACACGGGCATCGGCGAGCTGGCTGCGGCTCTT
	AATGAGTTTGACAATAAGATTATCCTGGACCCCATGACGTTCAGCGAGGCCAGGTTCC
	GGCCGTCCCTGGAGGAGAGGCTGGAGAGCATCATCAGCGGCGCAGCGCTGATGGCCGA
	CTCCTCCTGCACGCGAGACGACCGGCGCGAGAGGATCGTGGCGGAGTGCAACGCCGTG
	CGGCAGGCGCTCCAGGACCTGCTCAGCGAGTACATGAATAATACTGGAAGGAAAGAAA
	GAGACAGCTTCGGAAAGCAGTGATGGATCACATATCTGACTCTTTCCTGGAAACCAAT
	GTTCCTTTGCTAGTTCTCATTGAGGCTGCAAAGAGCGGAAATGAAAAGGAAGTGAAAG
	AATATGCCCAAGTTTTCCGTGAGCATGCCAACAAACTGGTAGAGGTTGCCAATTTGGC
	CTGTTCCATCTCCAACAATGAASAAGGGGTGAAATTAGTTCGGATGGCAGCCACCCAG
	ATTGACAGCCTGTGTCCCCAGGTCATCAATGCCGCTCTGACACTGGCTGCCCGGCCAC
	AGAGCAAAGTTGCTCAGGATAACATGGACGTCTTCAAAGACCAGTGGGAGAAGCAGGT
	CCGAGTGTTGACAGAGGCCGTGGATGACATCACCTCAGTGGATGACTTCCTCTCTGTC
	TCAGAAAATCACATCTTGGAGGATGTGAACAAGTGTGTGATAGCCCTCCAAGAGGGCG
	ATGTGGACACTCTGGACCGGACTGCAGGGGCCATCAGGGGCCGGGCAGCTCGAGTCAT
	ACACATCATCAATGCTGAGATGGAGAACTATGAAGCTGGGGTTTATACTGAGAAGGTG
	TTGGAAGCTACAAAATTGCTTTCTGAAACAGTGATGCCACGCTTCGCTGAACAAGTAG
	AGGTTGCCATTGAAGCCCTGAGTGCCAACGTTCCTCAACCGTTTGAGGAGAATGAGTT
	CATCGATGCCTCTCGCCTGGTGTATGATGGCGTTCGGGACATCAGAAAGGCTGTGCTG
	ATGATCAGGACCCCAGAAGAACTAGAGGATGATTCTGACTTTGAGCAGGAAGATTATG
	ATGTGCGTAGAGGGACAAGTGTTCAGACTGAGGATGACCAGCTCATTGCAGGGCAGAG
	CGCACGGGCCATCATGGCGCAACTACCGCAGGAGGAGAAGGCAAAAATAGCTGAGCAG
	GTGGAGATATTCCATCAAGAGAAAAGCAAGCTGGATGCAGAAGTGGCCAAATGGGACG
	ACAGCGGCAATGATATCATTGTACTGGCCAGCAGATGTGTATGATCATGATGGGAAAT
	GACAGACTTCACAAGAGGCAAAGGCCCATTGAAAAATACATCTGATGTCATTAATGCT
	GCCAAGAAAATTGCCGAAGCAGGTTCTCGAATGGACAAATTAGCTCGTGCTGTGGCTG
	ATCAGCTGGACAGTGCCACATCGCTTATCCAGGCAGCTAAAAACCTGATGAATGCTGT
	TGTCCTCACGGTGAAAGCATCCTATGTGGCCTCAACCAAATACCAGAAGGTCTATGGG
	ACAGCAGCTGTCAACTCACCTGTTGTGTCTTGGAAGATGAAGGCTCCAGAGAAGAAGC
	CCCTTGTGAAGAGAGAAAAGCCTGAAGAATTCCAGACACGAGTTCGACGAGGTTCTCA
	GAAGAAACACATTTCGCCTGTACAGGCTTTAAQTGAATTCAAAGCAATGGATTCCTTC
	TAGGACGATAGGTTTTAACAAGAAAGCTTTTTCTTTCTTTTCTTTCTTTCTTTTTCTT
	TTTAATTCCATTTTTGTATGCATACCTGCCAGCTCGTATGCCTCTGGCATGGGGAAAT
	TAAGGGAACAGTGTCTGTTTGCATGTAAGATGAGATGAGATCAATACTACTGATCCAT
	CTGTACCCTGCGAAGGAGACAGGACATTCCTGTACTAAGGTGGCACAGAGCTGTCCTT
	TGCAACATTCTCATAATATTGGGCACAGAGTTCGCATTGGCGCAATATTTATGGGAGT
	GGGAGGGATGGGGAAAATAAACTTAACTCTACAAAAGCAAACTCTAATGCATGCAAGA
	ATCATTAGGTTGGCAGGTATATGCATAAGTGAAAAATCTGGAAGTGTAATGGTAGAAC
	ATAAAACTTGTATTGCTTCTGTTTCAGTGCAAAAATGTACTAGCCAATACGCTTAAGT
	GTGTGGCCCATGAATTGAACAATTTAACCTTCAAGTCTATATCCGTGATATTATGTCG
	ATTTTTAACTGAGGGGAAATTAACTAGTCCAGCCTAAAATGCTTCTTTTAATCTGCAT
	TCTGTTTCCTCTTCTAGTTGTGCCATTACTAGTGATCATGTTTTTTTCCCCCCTTTAA
	TGAAAACAATAAACATCTATTTGAGACAATTAAAATCCTTCTGGGGGCACTGGAAGCA
	CAATACGGTGACCAATCTTGCTTTCATTTTTTTTTCTTTTTAATTTGAACCATGATTT
	TGCTAGAAATAGAAGGCCCAGTGGTGGAATATTAGAGGGAAGGAAACTGACAACGTGT
	GAAAGTTA
	ORE Start: ATG at 31		ORF Stop: TAG at 2611
	SEQ ID NO: 2	860 aa	MW at 95525.9 kD
NOV1a,	MTSATSPIILKWDPKSLEIRTLTVERLLEPLVTQVTTLVNTSNKGPSGKKKGRSKKAH
CG100653-01
Protein Sequence	VLAASVEQATONFLEKGEQIAKESQDLKEELVAAVEDVRKQGETMRIASSEFADDPCS
	SVKRGTMVRAARALLSAVTRLLILADMADVMRLLSHLKIVEEALEAVKNATNEQDLAN
	RFKEFGKKMVKLNYVAARRQQELKDPHCRDEMAAARGALKKNATMLYTASQAFLRHPD
	VAATRANRDYVFKQVQEAIAGISNAAQATSPTDEAKGHTGIGELAAALNEFDNKIILD
	PMTFSEARFRPSLEERLESIISGAALMADSSCTRDDRRERIVAECNAVRQALQDLLSE
	YMNNTGRKEKGDPLNIAIDKMTKKTRDLRRQLRKAVMDHISDSFLETNVPLLVLIEAA
	KSGNEKEVKEYAQVFREHANKLVEVANLACSISNNEEGVKLVRMAATQIDSLCPQVIN
	AALTLAARPQSKVAQDNMDVFKDQWEKQVRVLTEAVDDITSVDDFLSVSENHILEDVN
	KCVIALQEGDVDTLDRTAGAIRGRAARVIHIINAEMENYEAGVYTEKVLEATKLLSET
	VMPRFAEQVEVAIEALSANVPQPFEENEFIDASRLVYDGVRDIRKAVLMIRTPEELED
	DSDFEQEDYDVRRGTSVQTEDDQLIAGQSARAIMAQLPQEEKAKIAEQVEIFHQEKSK
	LDAEVAKWDDSGNDIIVLAKQMCMIMMEMTDFTRGKGPLKNTSDVINAAKKIAEAGSR
	MDKLARAVADQLDSATSLIQAAKNLMNAVVLTVKASYVASTKYQKVYGTAAVNSPVVS
	WKMKAPEKKPLVKREKPEEFQTRVRRGSQKKHISPVQALSEFKAMDSF

[0317] Further analysis of the NOV1a protein yielded the following properties shown in Table 1B.

TABLE 1B
Protein Sequence Properties NOV1a
PSort     0.3600 probability located in mitochondrial matrix space;
analysis: 0.3000 probability located in microbody (peroxisome); 0.1000
          probability located in lysosome (lumen); 0.0000 probability
          located in endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0318] A search of the NOV1a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1C.

TABLE 1C
Geneseq Results for NOV1a
		NOV1a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAR58778	Neural alpha-catenin protein -	1 . . . 860	851/906 (93%)	0.0
	Homo sapiens, 906 aa.	1 . . . 906	855/906 (93%)
	[JP06211898-A, 02-AUG-1994]
AAY07060	Renal cancer associated antigen	8 . . . 859	694/899 (77%)	0.0
	precursor sequence - Homo sapiens,	9 . . . 905	773/899 (85%)
	906 aa. [WO9904265-A2, 28-JAN-1999]
AAU32945	Novel human secreted protein	8 . . . 769	611/766 (79%)	0.0
	#3436 - Homo sapiens, 932 aa.	10 . . . 773	683/766 (88%)
	[WO200179449-A2, 25-OCT-2001]
ABG10622	Novel human diagnostic protein	8 . . . 769	610/766 (79%)	0.0
	#10613 - Homo sapiens, 932 aa.	10 . . . 773	682/766 (88%)
	[WO200175067-A2, 11-OCT-2001]
ABG10622	Novel human diagnostic protein	8 . . . 769	610/766 (79%)	0.0
	#10613 - Homo sapiens, 932 aa.	10 . . . 773	682/766 (88%)
	[WO200175067-A2, 11-OCT-2001]

[0319] In a BLAST search of public sequence databases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1D.

TABLE 1D
Public BLASTP Results for NOV1a
		NOV1a	Identities/
Protein		Residues/	Similarities for the
Accession		Match	Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P30997	Alpha-2 catenin (Alpha N-catenin)	1 . . . 860	851/906 (93%)	0.0
	(Neural alpha-catenin) - Gallus	1 . . . 906	855/906 (93%)
	gallus (Chicken), 906 aa.
I49499	alpha N-catenin I - mouse, 905 aa.	1 . . . 860	850/905 (93%)	0.0
		1 . . . 905	854/905 (93%)
A45011	alpha-catenin 2 - human, 945 aa.	1 . . . 769	768/770 (99%)	0.0
		1 . . . 770	768/770 (99%)
P26232	Alpha-2 catenin (Alpha-catenin	1 . . . 769	768/770 (99%)	0.0
	related protein) (Alpha N-catenin) -	1 . . . 770	768/770 (99%)
	Homo sapiens (Human), 953 aa.
Q61301	Alpha-2 catenin (Alpha-catenin	1 . . . 769	759/770 (98%)	0.0
	related protein) (Alpha N-catenin) -	1 . . . 770	762/770 (98%)
	Mus musculus (Mouse), 953 aa.

[0320] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1E.

TABLE 1E
Domain Analysis of NOV1a
		Identities/
	NOV1a	Similarities for
Pfam Domain	Match Region	the Matched Region	Expect Value
Vinculin	18 . . . 765	424/948 (45%)	0
		736/948 (78%)
Vinculin	766 . . . 821	32/57 (56%)	5.4e−30
		56/57 (98%)

Example 2.

[0321] The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.

TABLE 2A
NOV2 Sequence Analysis
	SEQ ID NO:3	2883 bp
NOV2a,	CGTGAATGGTGTAGTGAGTTCTAATGAAACTTTATTTACAAGAGGAGACTGACCAGGT
CG100689-01
DNA Sequence	TTGGCCTGGGGGCCACAGTGTGTAGACCCCTGGAAAGATACATCCTGAGAAGAAAAAA
	AGAATATATGCAGGAATGCTTAACTTTGTGGGTTTTCTCTCCTCTTGCCCTCACTGAC
	TCAGGATACACAAAGACCTATCAAGCTCACGCAAAGCAGAAATTCAGCCGCTTATGGT
	CCAGCAAGTCTGTCACTGAGATTCACCTATACTTTGAGGAGGAAGTCAAGCAAGAAGA
	ATGTGACCATTTGGACCGCCTTTTTGCTCCCAAGGAAGCTGGGAAACAGCCACGTACA
	GTGATCATTCAAGGACCACAAGGAATTGGAAAAACGACACTCCTGATGAAGCTGATGA
	TGGCCTGGTCGGACAACAAGATCTTTCGGGATAGGTTCCTGTACACGTTCTATTTCTG
	CTGCAGAGAACTGAGGGAGTTGCCGCCAACGAGTTTGGCTGACTTGATTTCCAGAGAG
	TGGCCTGACCCCGCTGCTCCTATAACAGAGATCGTGTCTCAACCGGAGAGACTCTTGT
	TCGTCATCGACAGCTTCGAAGAGCTGCAGGGCGGCTTGAACGAACCCGATTCGGATCT
	GTGTGGTGACTTGATGGAGAAACGGCCGGTGCAGGTGCTTCTGAGCAGTTTGCTGAGG
	AAGAAGATGCTCCCGGAGGCCTCCCTGCTCATCGCTATCAAACCCGTGTGCCCGAAGG
	AGCTCCGGGATCAGGTGACGATCTCAGAAATCTACCAGCCCCGGGGATTCAACGAGAG
	TGATAGGTTAGTGTATTTCTGCTGTTTCTTCAAAGACCCGAAAAGAGCCATGGAAGCC
	TTCAATCTTGTAAGAGAAAGTGAACAGCTGTTTTCCATATGCCAAATCCCGCTCCTCT
	GCTGGATCCTGTGTACCAGTCTGAAGCAAGAGATGCAGAAAGGAAAAGACCTGGCCCT
	GACCTGCCAGAGCACTACCTCTGTGTACTCCTCTTTCGTCTTTAACCTGTTCACACCT
	GAGGGTGCCGAGGGCCCGACTCCGCAAACCCAGCACCAGCTGAAGGCCCTGTGCTCCC
	TGGCTGCAGAGGGTATGTGGACAGACACATTTGAGTTTTGTGAAGACGACCTCCGGAG
	AAATGGGGTTGTTGACGCTGACATCCCTGCGCTGCTGGGCACCAAGATACTTCTGAAG
	TACGGGGAGCGTGAGAGCTCCTACGTGTTCCTCCACGTGTGTATCCAGGAGTTCTGTG
	CCGCCTTGTTCTATTTGCTCAAGAGCCACCTTGATCATCCTCACCCAGCTGTGAGATG
	TGTACAGGAATTGCTAGTTGCCAATTTTGAAAAAGCAAGGACAGCACATTGGATTTTT
	TTGGGGTGTTTTCTAACTGGCCTTTTAAATAAAAAGGAACAAGAAAAACTGGATGCGT
	TTTTTGGCTTCCAACTGTCCCAAGAGATAAAGCAGCAAATTCACCAGTGCCTGAAGAG
	CTTAGGGGAGCGTGGCAATCCTCAGGGACAGGTGGATTCCTTGGCGATATTTTACTGT
	CTCTTTGAAATGCAGGATCCTGCCTTTGTGAAGCAGGCAGTGAACCTCCTCCAAGAAG
	CTAACTTTCATATTATTGACAACGTGGACTTGGTGGTTTCTGCCTACTGCTTAAAATA
	CTGCTCCAGCTTGAGGAAACTCTGTTTTTCCGTTCAAAATGTCTTTAAGAAAGAGGAT
	GAACACAGCTCTACGTCGGATTACAGCCTCATCTGTTGGCATCACATCTGCTCTGTGC
	TCACCACCAGCGGGCACCTCAGAGAGCTCCAGGTGCAGGACAGCACCCTCAGCGAGTC
	GACCTTTGTGACCTGGTGTAACCAGCTGAGGCATCCCAGCTGTCGCCTTCAGAAGCTT
	GGAATAAATAACGTTTCCTTTTCTGGCCAGAGTGTTCTGCTCTTTGAGGTGCTCTTTT
	ATCAGCCAGACTTGAAATACCTGAGCTTCACCCTCACGAAACTCTCTCGTGATGACAT
	CAGGTCCCTCTGTGATGCCTTGAACTACCCAGCAGGCAACGTCAAAGAGCTAGCGCTG
	GTAAATTGTCACCTCTCACCCATTGATTGTGAAGTCCTTGCTGGCCTTCTAACCAACA
	ACAAGAAGCTGACGTATCTGAATGTATCCTGCAACCAGTTAGACACAGGCGTGCCCCT
	TTTGTGTGAASCCCTGTGCAGCCCAGACACGGTCCTGGTATACCTGATGTTGGCTTTC
	TGCCACCTCAGCGAGCAGTGCTGCGAATACATCTCTGAAATGCTTCTGCGTAACAAGA
	GCGTGCGCTATCTAGACCTCAGTGCCAATGTCCTGAAGGACGAAGGACTGAAAACTCT
	CTGCGAGGCCTTGAAACATCCGGACTGCTGCCTGGATTCACTGTGTTTGGTAAAATGT
	TTTATCACTGCTGCTGGCTGTGAAGACCTCGCCTCTGCTCTCATCAGCAATCAAAACC
	TGAAGATTCTGCAAATTGGGTGCAATGAAATCGGAGATGTGGGTGTGCAGCTGTTGTG
	TCGGGCTCTGACGCATACGGATTGCCGCTTAGAGATTCTTGGGTTGGAAGAATGTGGG
	TTAACGAGCACCTGCTGTAAGGATCTCGCGTCTGTTCTCACCTGCAGTAAGACCCTGC
	AGCAGCTCAACCTGACCTTGAACACCTTGGACCACACAGGGGTGGTTGTACTCTGTGA
	GGCCCTGAGACACCCAGAGTGTGCCCTGCAGGTGCTCGGGCTGAGAAAAACTGATTTT
	GATGAGGAAACCCAGGCACTTCTGACGGCTGAGGAAGAGAGAAATCCTAACCTGACCA
	TCACAGACGACTGTGACACAATCACAAGGGTAGAGATCTGA
	ORF Start: ATG at 124		ORF Stop: TGA at 2881
	SEQ ID NO:4	919 aa	MW at 103966.7 kD
NOV2a,	MQECLTLWVFSPLALTDSGYTKTYQAHAKQKFSRLWSSKSVTEIHLYFEEEVKQEECD
CG100689-01
Protein Sequence	HLDRLFAPKEAGKQPRTVIIQGPQGIGKTTLLMKLMMAWSDNKIFRDRFLYTFYFCCR
	ELRELPPTSLADLISREWPDPAAPITEIVSQPERLLFVIDSFEELQGGLNEPDSDLCG
	DLMEKRPVQVLLSSLLRKKMLPEASLLIAIKPVCPKELRDQVTISEIYQPRGFNESDR
	LVYFCCFFKDPKRAMEAFNLVRESEQLFSICQIPLLCWILCTSLKQEMQKGKDLALTC
	QSTTSVYSSFVFNLFTPEGAEGPTPQTQHQLKALCSLAAEGMWTDTFEFCEDDLRRNG
	VVDADIPALLGTKILLKYGERESSYVFLHVCIQEFCAALFYLLKSHLDHPHPAVRCVQ
	ELLVANFEKARRAHWIFLGCFLTGLLNKKEQEKLDAFFGFQLSQEIKQQIHQCLKSLG
	ERGNPQGQVDSLAIFYCLFEDQDPAFVKQAVNLLQEANFHIIDNVDLVVSAYCLKYCS
	SLRKLCFSVQNVFKKEDEHSSTSDYSLICWHHICSVLTTSGHLRELQVQDSTLSESTF
	VTWCNQLRHPSCRLQKLGINNVSFSGQSVLLFEVLFYQPDLKYLSFTLTKLSRDDIRS
	LCDALNYPAGNVKELALVNCHLSPIDCEVLAGLLTNNKKLTYLNVSCNQLDTGVPLLC
	EALCSPDTVLVYLMLAFCHLSEQCCEYISEMLLRNKSVRYLDLSANVLKDEGLKTLCE
	ALKHPDCCLDSLCLVKCFITAAGCEDLASALISNQNLKILQIGCNEIGDVGVQLLCRA
	LTHTDCRLEILGLEECGLTSTCCKDLASVLTCSKTLQQLNLTLNTLDHTGVVVLCEAL
	RHPECALQVLGLRKTDFDEETQALLTAEEERNPNLTITDDCDTITRVEI

[0322] Further analysis of the NOV2a protein yielded the following properties shown in Table 2B.

TABLE 2B
Protein Sequence Properties NOV2a
PSort     0.6000 probability located in nucleus; 0.3000 probability
analysis: located in microbody (peroxisome); 0.2000 probability located
          in endoplasmic reticulum (membrane);
          0.1000 probability located in mitochondrial inner membrane
SignalP   Cleavage site between residues 17 and 18
analysis:

[0323] A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2C.

TABLE 2C
Geneseq Results for NOV2a
		NOV2a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAM50328	Human nucleotide binding site	33 . . . 882	849/850 (99%)	0.0
	protein NBS-5 - Homo sapiens, 858	1 . . . 850	850/850 (99%)
	aa. [WO200183753-A2, 08-NOV-2001]
AAU07878	Polypeptide sequence for	165 . . . 907	375/743 (50%)	0.0
	mammalian Spg65 - Mammalia,	5 . . . 744	528/743 (70%)
	748 aa. [WO200166752-A2, 13-SEP-2001]
AAE07514	Human PYRIN-1 protein - Homo	20 . . . 907	320/926 (34%)	e−146
	sapiens, 1034 aa. [WO200161005-	134 . . . 1028	491/926 (52%)
	A2, 23-AUG-2001]
AAG65895	Amino acid sequence of GSK gene	75 . . . 907	301/849 (35%)	e−137
	Id 97078 - Homo sapiens, 1062 aa.	208 . . . 1043	460/849 (53%)
	[WO200172961-A2, 04-OCT-2001]
AAE07513	Human nucleotide binding site 1	75 . . . 907	299/849 (35%)	e−134
	(NBS-1) protein - Homo sapiens,	180 . . . 1014	459/849 (53%)
	1033 aa. [WO200161005-A2, 23-AUG-2001]

[0324] In a BLAST search of public sequence databases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2D.

TABLE 2D
Public BLASTP Results for NOV2a
			Identities/
		NOV2a	Similarities
Protein		Residues/	for the
Accession		Match	Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96MN2	CDNA FLJ32126 FIS, CLONE	1 . . . 919	918/919 (99%)	0.0
	PEBLM2000112, WEAKLY	1 . . . 919	918/919 (99%)
	SIMILAR TO HOMO SAPIENS
	NUCLEOTIDE-BINDING SITE
	PROTEIN 1 MRNA - Homo sapiens
	(Human), 919 aa.
Q96MN2	NACHT-, LRR- and PYD-containing	18 . . . 919	900/902 (99%)	0.0
	protein 4 (PAAD and NACHT-	93 . . . 994	901/902 (99%)
	containing protein 2) (PYRIN-
	containing APAF1-like protein 4)
	(Ribonuclease inhibitor 2) - Homo
	sapiens (Human), 994 aa.
AAL88672	RIBONUCLEASE INHIBITOR 2 -	18 . . . 919	894/902 (99%)	0.0
	Homo sapiens (Human), 916 aa.	15 . . . 916	897/902 (99%)
CAD19386	SEQUENCE 7 FROM PATENT	33 . . . 882	849/850 (99%)	0.0
	WO0183753 - Homo sapiens (Human),	1 . . . 850	850/850 (99%)
	858 aa (fragment).
Q99MW0	RIBONUCLEASE/ANGIOGENIN	165 . . . 907	374/743 (50%)	0.0
	INHIBITOR 2 - Mus musculus	5 . . . 744	528/743 (70%)
	(Mouse), 748 aa.

[0325] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2E.

TABLE 2E
Domain Analysis of NOV2a
		Identities/
	NOV2a	Similarities for
Pfam Domain	Match Region	the Matched Region	Expect Value
SRP54	71 . . . 93	11/23 (48%)	0.18
		17/23 (74%)

Example 3

[0326] The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.

TABLE 3A
NOV3 Sequence Analysis
	SEQ ID NO:5	2142 bp
NOV3a,	TATTATTCAGCAAACAATCTCAATGTGTTCCTGATGGGAGAGAGAGCATCTGGAAAAA
CG100760-01
DNA Sequence	CTATTGTTATAAATCTGGCTGTGTTGAGGTGGATCAAGGGTGAGATGTGGCAGAACAT
	GATCTCGTACGTCGTTCACCTCACTGCTCACGAAATAAACCAGATGACCAACAGCAGC
	TTGGCTGAGCTAATCGCCAAGGACTGGCCTGACGGCCAGGCTCCCATTGCAGACATCC
	TGTCTGATCCCAAGAAACTCCTTTTCATCCTCGAGGACTTGGACAACATAAGATTCGA
	GTTAAATGTCAATGAAAGTGCTTTGTGTAGTAACAGCACCCAGAAAGTTCCCATTCCA
	GTTCTCCTGGTCAGTTTGCTGAAGAGAAAAATGGCTCCAGGCTGCTGGTTCCTCATCT
	CCTCAAGGCCCACACGTGGGAATAATGTAAAACGTTCTTGAAAAGAGGTAGATTGCTG
	CACGACCTTGCAGCTGTCGAATGGGAAGAGGGAGATATATTTTTCTCTTTCTTTTAAA
	GACCGCCAGAGGGCGTCGGCAGCCCTCCAGCTTGTACATGAGGATGAAATACTCGTGG
	GTCTGTGCCGAGTCGCCATCTTATGCTGGATCACGTGTACTGTCCTGAAGCGGCAGAT
	GGACAAGGGGCGTGACTTCCAGCTCTGCTGCCAAACACCCACTGATCTACATGCCCAC
	TTTCTTGCTGATGCGTTGACATCAGAGGCTGGACTTACTGCCAATCAGTATCACCTAG
	GTCTCCTAAAACGTCTGTGTTTGCTGGCTGCAGGAGGACTGTTTCTGAGCACCCTGAA
	TTTCAGTGGTGAAGACCTCAGATGTGTTGGGTTTACTGAGGCTGATGTCTCTGTGTTG
	CAGGCCGCGAATATTCTTTTGCCGAGCAACACTCATAAAGACCGTTACAAGTTCATAC
	ACTTGAACGTCCAGGAGTTTTGTACAGCCATTGCATTTCTGATGGCAGTACCCAACTA
	TCTGATCCCCTCAGGCAGCAGAGAGTATAAAGAGAAGAGAGAACAATACTCTGACTTT
	AATCAAGTGTTTACTTTCATTTTTGGTCTTCTAAATGCAAACAGGAGAAAGATTCTTG
	AGACATCCTTTGGATACCAGCTACCGATGGTAGACAGCTTCAAGTGGTACTCGGTGGG
	ATACATGAACATTTGGACCGTGACCCGGAAAAGTTGACGCACCATATGCCTTTGTTT
	TACTGTCTCTATGAGAATCGGGAAGAAGAATTTGTGAAGACGATTGTGGATGCTCTCA
	TGGAGGTTACAGTTTACCTTCAATCAGACAAGGATATGATGGTCTCATTATACTGTCT
	GGATTACTGCTGTCACCTGAGGACACTTAAGTTGAGTGTTCAGCGCATCTTTCAAAAC
	AAACTGGAGAAATGCAACTTGTCGGCAGCCAGCTGTCAGGACCTAGCCTTGTTTCTCA
	CCAGCATCCAACACGTAACTCGATTGTGCCTGGGATTTAATCGGCTCCAAGATGATGG
	CATAAAGCTATTGTGTGCGGCCCTGACTCACCCCAAGTGTGCCTTAGAGAGACTGGAG
	CTCTGGTTTTGCCAGCTGGCAGCACCCGCTTGCAAGCACTTGTCAGATGCTCTCCTGC
	AGAACAGGAGCCTGACACACCTGAATCTGAGCAAGAACAGCCTGAGAGACGAGGGAGT
	CAAGTTCCTGTGTGAGGCCTTGGGTCGCCCAGATGGTAACCTGCAGAGCCTGAGTTTG
	TCAGGTTGTTCTTTCACAAGAGAGGGCTGTGGAGAGCTGGCTAATGCCCTCAGCCATA
	ATCATAATGTGAAAATCTTGGATTTGGGAGAAAATGATCTTCAGGATGATGGAGTGAA
	GCTACTGTGTGAGGCTCTGAAACCACATCGTGCATTGCACACACTTGGGTTGGCGAAA
	TGCAATCTGACAACTGCTTGCTGCCAGCATCTCTTCTCTGTTCTCAGCAGCAGTAAGA
	GCCTGGTCAATCTGAACCTTCTAGGCAATGAATTGGATACTGATGGTGTCAAGATGCT
	ATGTAAGGCTTTGAAAAAGTCGACATGCAGGCTGCAGAAACTCGGGTAAACCTCACTG
	ACTTTTCTGCAGGGGAGAACATACAGGGACAAGGCTAGATTGACTAGGCTTCTA
	ORF Start: ATG at 34		ORF Stop: TAA at 2077
	SEQ ID NO:6	681aa	MW at 76724.1 kD
NOV3a,	MGERASGKTIVINLAVLRWIKGEMWQNMISYVVHLTAHEINQMTNSSLAELIAKDWPD
CG100760-01
Protein Sequence	GQAPIADILSDPKKLLFILEDLDNIRFELNVNESALCSNSTQKVPIPVLLVSLLKRKM
	APGCWFLISSRPTRGNNVKTFLKEVDCCTTLQLSNGKREIYFNSFFKDRQRASAALQL
	VHEDEILVGLCRVAILCWITCTVLKRQMDKGRDFQLCCQTPTDLHAHFLADALTSEAG
	LTANQYHLGLLKRLCLLAAGGLFLSTLNFSGEDLRCVGFTEADVSVLQAANILLPSNT
	HKDRYKFIHLNVQEFCTAIAFLMAVPNYLIPSGSREYKEKREQYSDFNQVFTFIFGLL
	NANRRKILETSFGYQLPMVDSFKWYSVGYMKHLDRDPEKLTHHMPLFYCLYENREEEF
	VKTIVDALMEVTVYLQSDKDMMVSLYCLDYCCHLRTLKLSVQRIFQNKLEKCNLSAAS
	CQDLALFLTSIQHVTRLCLGFNRLQDDGIKLLCAALTHPKCALERLELWFCQLAAPAC
	KHLSDALLQNRSLTHLNLSKNSLRDEGVKFLCEALGRPDGNLQSLSLSGCSFTREGCG
	ELANALSHNHNVKILDLGENDLQDDGVKLLCEALKPHRALHTLGLAKCNLTTACCQHL
	FSVLSSSKSLVNLNLLGNELDTDGVKMLCKALKKSTCRLQKLG

[0327] Further analysis of the NOV3a protein yielded the following properties shown in Table 3B.

TABLE 3B
Protein Sequence Properties NOV3a
PSort     0.8200 probability located in endoplasmic reticulum
analysis: (membrane); 0.1900 probability located in plasma membrane;
          0.1000 probability located in endoplasmic reticulum (lumen);
          0.1000 probability located in outside
SignalP   Cleavage site between residues 23 and 24
analysis:

[0328] A search of the NOV3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3C.

TABLE 3C
Geneseq Results for NOV3a
		NOV3a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAM50330	Human nucleotide binding site	1 . . . 681	539/745 (72%)	0.0
	protein NBS-3 - Homo sapiens, 875	116 . . . 859	587/745 (78%)
	aa. [WO200183753-A2, 08-NOV-2001]
AAM50326	Human nucleotide binding site	1 . . . 510	469/517 (90%)	0.0
	protein NBS-3 - Homo sapiens, 631	116 . . . 631	479/517 (91%)
	aa. [WO200183753-A2, 08-NOV-2001]
AAM50328	Human nucleotide binding site	2 . . . 681	247/750 (32%)	e−105
	protein NBS-5 - Homo sapiens, 858	48 . . . 792	381/750 (49%)
	aa. [WO200183753-A2, 08-NOV-2001]
AAE07514	Human PYRIN-1 protein - Homo	2 . . . 680	238/729 (32%)	e−100
	sapiens, 1034 aa. [WO200161005-	224 . . . 944	362/729 (49%)
	A2, 23-AUG-2001]
ABG03924	Novel human diagnostic protein	2 . . . 680	228/741 (30%)	7e−78
	#3915 - Homo sapiens, 952 aa.	178 . . . 908	334/741 (44%)
	[WO200175067-A2, 11-OCT-2001]

[0329] In a BLAST search of public sequence databases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3D.

TABLE 3D
Public BLASTP Results for NOV3a
		NOV3a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
CAD19388	SEQUENCE 15 FROM PATENT	1 . . . 681	539/745 (72%)	0.0
	WO0183753 - Homo sapiens	116 . . . 859	587/745 (78%)
	(Human), 875 aa.
CAD19384	SEQUENCE 3 FROM PATENT	1 . . . 510	469/517 (90%)	0.0
	WO0183753 - Homo sapiens	116 . . . 631	479/517 (91%)
	(Human), 631 aa (fragment).
CAD19386	SEQUENCE 7 FROM PATENT	2 . . . 681	247/750 (32%)	e−104
	WO0183753 - Homo sapiens	48 . . . 792	381/750 (49%)
	(Human), 858 aa (fragment).
Q96MN2	CDNA FLJ32126 FIS, CLONE	2 . . . 681	247/750 (32%)	e−104
	PEBLM2000112, WEAKLY	80 . . . 824	381/750 (49%)
	SIMILAR TO Homo sapiens
	NUCLEOTIDE-BINDING SITE
	PROTEIN 1 MRNA - Homo sapiens
	(Human), 919 aa.
Q96MN2	NACHT-, LRR- and PYD-containing	2 . . . 681	247/750 (32%)	e−104
	protein 4 (PAAD and NACHT-	155 . . . 899	381/750 (49%)
	containing protein 2) (PYRIN-
	containing APAF1-like protein 4)
	(Ribonuclease inhibitor 2) - Homo
	sapiens (Human), 994 aa.

Example 4

[0330] The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A.

TABLE 4A
NOV4 Sequence Analysis
	SEQ ID NO:7	782 bp
NOV4a,	TCTCAAGGGATAATCACTAAATTCTGCCGAAAGGACTGAGGAACGGTGCCTGGAAAAG
CG100851-02
DNA Sequence	GGCAAGAATATCACGGCATGGGCATGAGTAGCTTGAAACTGCTGAAGTATGTCCTGTT
	TTTCTTCAACTTGCTCTTTTGGATCTGTGGCTGCTGCATTTTGGGCTTTGGGATCTAC
	CTGCTGATCCACAACAACTTCGGAGTGCTCTTCCATAACCTCCCCTCCCTCACGCTGG
	GCAATGTGTTTGTCATCGTGGGCTCTATCAAGGAAAACAAGTGTCTGCTTATGTCGTT
	CTTCATCCTGCTGCTGATTATCCTCCTTGCTGAGGTGACCTTGGCCATCCTGCTCTTT
	GTATATGAACAGAAGCTGAATGAGTATGTGGCTAAGGGTCTGACCGACAGCATCCACC
	GTTACCACTCAGACAATAGCACCAAGGCAGCGTGGGACTCCATCCAGTCATTTCTGCA
	GTGTTGTGGTATAAATGGCACGAGTGATGGGACCAGTGGCCCACCAGCATCTTGCCCC
	TCAGATCGAAAAGTGGAGGGTTGCTATGCGAAAGCAAGACTGTGGTTTCATTCCAATT
	TCCTGTATATCGGAATCATCACCATCTGTGTATGTGTGATTGAGGTGTTGGGGATGTC
	CTTTGCACTGACCCTGAACTGCCAGATTGACAAAACCAGCCAGACCATAGGGCTATGA
	TCTGCAGTAGTTCTGTGGTGAAGAGACTTGTTTCATCTCCTGGAAATGCAAAACCATT
	TATAGCATGAGCCCTACATGATCATCAG
	ORF Start: ATG at 76		ORF Stop: TGA at 694
	SEQ ID NO:8	206aa	MW at 22888.8 kD
NOV4a,	MGMSSLKLLKYVLFFFNLLFWICGCCILGFGIYLLIHNNFGVLFHNLPSLTLGNVFVI
CG100851-02
Protein Sequence	VGSIKENKCLLMSFFILLLIILLAEVTLAILLFVYEQKLNEYVAKGLTDSIHRYHSDN
	STKAAWDSIQSFLQCCGINGTSDGTSGPPASCPSDRKVEGCYAKARLWFHSNFLYIGI
	ITICVCVIEVLGMSFALTLNCQIDKTSQTIGL

[0331] Further analysis of the NOV4a protein yielded the following properties shown in Table 4B.

TABLE 4B
Protein Sequence Properties NOV4a
PSort     0.6400 probability located in plasma membrane;
analysis: 0.4600 probability located in Golgi body;
          0.3700 probability located in endoplasmic
          reticulum (membrane); 0.1000 probability located
          in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 32 and 33
analysis:

[0332] A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4C.

TABLE 4C
Geneseq Results for NOV4a
		NOV4a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAY96141	Human haematopoietic CD53 -	1 . . . 206	205/219 (93%)	e−115
	Homo sapiens, 219 aa.	1 . . . 219	205/219 (93%)
	[US6111093-A, 29-AUG-2000]
AAB58136	Lung cancer associated polypeptide	1 . . . 206	205/219 (93%)	e−115
	sequence SEQ ID 474 - Homo	13 . . . 231	205/219 (93%)
	sapiens, 231 aa. [WO200055180-
	A2, 21-SEP-2000]
AAW89152	Human CD53 antigen - Homo	1 . . . 206	205/219 (93%)	e−115
	sapiens, 219 aa. [US5849898-A, 15-DEC-1998]	1 . . . 219	205/219 (93%)
AAW80455	Human CD53 antigen - Homo	1 . . . 206	205/219 (93%)	e−115
	sapiens, 219 aa. [US5830731-A, 03-NOV-1998]	1 . . . 219	205/219 (93%)
AAR91446	Human CD53 antigen - Homo	1 . . . 206	205/219 (93%)	e−115
	sapiens, 219 aa. [US5506126-A, 09-APR-1996]	1 . . . 219	205/219 (93%)

[0333] In a BLAST search of public sequence databases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4D.

TABLE 4D
Public BLASTP Results for NOV4a
		NOV4a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P19397	Leukocyte surface antigen CD53	1 . . . 206	205/219 (93%)	e−115
	(Cell surface glycoprotein CD53) -	1 . . . 219	205/219 (93%)
	Homo sapiens (Human), 219 aa.
AAH21310	CD53 ANTIGEN - Mus musculus	1 . . . 206	168/219 (76%)	6e−95
	(Mouse), 219 aa.	1 . . . 219	183/219 (82%)
Q61451	Leukocyte surface antigen CD53	2 . . . 206	167/218 (76%)	2e−94
	(Cell surface glycoprotein CD53) -	1 . . . 218	182/218 (82%)
	Mus musculus (Mouse), 218 aa.
A39574	leukocyte antigen OX-44 - rat, 219	1 . . . 206	164/219 (74%)	7e−94
	aa.	1 . . . 219	183/219 (82%)
P24485	Leukocyte surface antigen CD53	2 . . . 206	163/218 (74%)	3e−93
	(Cell surface glycoprotein CD53)	1 . . . 218	182/218 (82%)
	(Leukocyte antigen MRC OX-44) -
	Rattus norvegicus (Rat), 218 aa.

[0334] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4E.

TABLE 4E
Domain Analysis of NOV4a
		Identities/
	NOV4a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
transmembrane4	10 . . . 36	17/27 (63%)	4.4e−08
		27/27 (100%)
transmembrane4	58 . . . 197	52/202 (26%)	1.2e−44
		120/202 (59%)

Example 5

[0335] The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5A.

TABLE 5A
NOV5 Sequence Analysis
	SEQ ID NO:9	1719 bp
NOV5a,	ATGCGGACGCCGGTGGTGATGACGCTGGGCATGGTGTTGGCGCCCTGCGGGCTCCTGC
CG101068-01
DNA Sequence	TCAACCTGACCGGCACCCTGGCGCCCGGCTGGCGGCTGGTGAAGGGCTTCCTGAACCA
	GCCAGTGGACGTGGAGTTGTACCAGGGCCTGTGGGACATGTGTCGCGAGCAGAGCAGC
	CGCGAGCGCGAGTGCGGCCAGACGGACCAGTGGGGCTACTTCGAGGCCCAGCCCGTGC
	TGGTGGCGCGGGCACTCATGGTCACCTCGCTGGCCGCCACGGTCCTGGGGCTTCTGCT
	GGCGTCGCTGGGCGTGCGCTGCTGGCAGGACGAGCCCAACTTCGTGCTGGCAGGGCTC
	TCGGGCGTCGTGCTCTTCGTCGCTGGCCTCCTCGGCCTCATCCCGGTGTCCTGGTACA
	ACCACTTCTTGGGGGACCGCGACGTGCTGCCCGCCCCGGCCAGCCCGGTCACGGTGCA
	GGTCAGCTACAGCCTGGTCCTGGGCTACCTGGGCAGCTGCCTCCTGCTGCTGGGCGGC
	TTCTCGCTGGCGCTCAGCTTCGCGCCCTGGTGCGACGAGCGTTGTCGCCGCCGCCGCA
	AGGGACCCTCCGCCGGGCCTCGCCGCAGCAGCGTCAGCACCATCCAAGTGGAGTGGCC
	CGAGCCCGACCTGGCGCCCGCCATCAAGTACTACAGCGACGGCCAGCACCGACCGCCG
	CCTGCCCAGCACCGCAAGCCCAAGCCCAAGCCCAAGGTCGGCTTCCCCATGCCGCGGC
	CGCGGCCCAAGGCCTACACCAACTCGGTGGACGTCCTCGACGGGGAGGGGTGGGAGTC
	CCAGGACGCTCCCTCGTGCAGCACCCACCCCTGCGACAGCTCGCTGCCCTGCGACTCC
	GACCTCTAGACGCTTGTAGAGCCTGGGGGGCGCCGGGTGGCAAAGGACTCACCCCCGC
	ACAGGCCCGCCTGGCTTCGAGTTGGAACCCGGACACTTGCCCCTCACTGGTGTGGATG
	GAAATCTGCCTTTCGTGGGACCAAACAGGACTCCTTGGACGATTAGTTCAGGTTGGGT
	TTGGTTTTCTTCTTAAAGAGTTTAGTTTTCCTCTCCAGAGGGATCAGGGTCCTCTTAG
	GGAGTGACCGGCTTTTCATATATTTTTGCTGAAGAATATATGGAAAGGGTGCCATTTG
	CGTCACGTGGACCAGGGACAGTGCTGAAATCAGCAGTGCTCAGAAACAATTTAACATG
	TTGAAACGACAATATTCTAAAATACTGATGAATCTTGCATCAATATAATTATTGGGTT
	TTTTTTCTTTTTCCTGCTGTATAACTCCTTGCCATGCAAACTCTCAAGAGGCCAATAT
	ATTCCTGGCCATGTTTGAATGAGCCTCTTAAAATAAACTTAGAGCCATGCAAATGCCA
	GCAGCTTAATGGATTTCATGGAATGAAATACCGTGATTAACTCATAGCTACATATCAT
	TGCATAAATQGGATTTATCTTTTTTCTCACTTATTTTTGCGGTGAAAGTCGAGGGCAT
	GCAAGAGTTTCTCTTCCAGAAGCCAAGAGGAGAACAAAGGTCCTAATGCTGTACTATT
	CCACCCTTTGGACGCCTCATCCAGGACGCAGAGGACTCTAGGTTTAACATTTTGTACA
	AAATGGAACCTGTTAATCATATTAAAGCACATATGTATATATCTTTTATTTATAAATA
	AAATTTTAAAACAATAGTTTCAGTATAGCCACAAAAA
	ORF Start: ATG at 1		ORF Stop: TAG at 877
	SEQ ID NO:10	292 aa	MW at 31914.5 kD
NOV5a,	MRTPVVMTLGMVLAPCGLLLNLTGTLAPGWRLVKGFLNQPVDVELYQGLWDMCREQSS
CG101068-01	RERECGQTDQWGYFEAQPVLVAPALMVTSLAATVLGLLLASLGVRCWQDEPNFVLAGL
Protein Sequence
	SGVVLFVAGLLGLIPVSWYNHFLGDRDVLPAPASPVTVQVSYSLVLGYLGSCLLLLGG
	FSLALSFAPWCDERCRRRRKGPSAGPRRSSVSTIQVEWPEPDLAPAIKYYSDGQHRPP
	PAQHRKPKPKPKVGFPMPRPRPKAYTNSVDVLDGEGWESQDAPSCSTHPCDSSLPCDS
	DL

[0336] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B.

TABLE 5B
Protein Sequence Properties NOV5a
PSort     0.6400 probability located in plasma membrane;
analysis: 0.4600 probability located in Golgi body; 0.3700 probability
          located in endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 28 and 29
analysis:

[0337] A search of the NOV5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 5C.

TABLE 5C
Geneseq Results for NOV5a
		NOV5a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB64401	Amino acid sequence of human	9 . . . 206	74/206 (35%)	1e−16
	intracellular signalling molecule	9 . . . 209	101/206 (48%)
	INTRA33 - Homo sapiens, 217 aa.
	[WO200077040-A2, 21-DEC-2000]
AAG75467	Human colon cancer antigen protein	6 . . . 187	59/188 (31%)	2e−13
	SEQ ID NO: 6231 - Homo sapiens,	7 . . . 192	92/188 (48%)
	210 aa. [WO200122920-A2, 05-APR-2001]
ABB50278	Claudin 4 ovarian tumor marker	6 . . . 187	59/188 (31%)	2e−13
	protein, SEQ ID NO: 45 - Homo	6 . . . 191	92/188 (48%)
	sapiens, 209 aa. [WO200175177-A2,
	11-OCT-2001]
AAB43133	Human ORFX ORF2897	6 . . . 187	59/188 (31%)	2e−13
	polypeptide sequence SEQ ID	6 . . . 191	92/188 (48%)
	NO: 5794 - Homo sapiens, 209 aa.
	[WO200058473-A2, 05-OCT-2000]
ABB50396	Human secreted protein encoded by	9 . . . 187	59/185 (31%)	2e−13
	gene 96 SEQ ID NO: 344 - Homo	1 . . . 183	91/185 (48%)
	sapiens, 202 aa. [WO200162891-A2, 30-AUG-2001]

[0338] In a BLAST search of public sequence databases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5D.

TABLE 5D
Public BLASTP Results for NOV5a
		NOV5a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96B33	SIMILAR TO RIKEN CDNA	28 . . . 292	252/267 (94%)	e−147
	2310014B08 GENE - Homo	2 . . . 268	254/267 (94%)
	sapiens (Human), 268 aa
	(fragment).
Q9D7D7	2310014B08RIK PROTEIN	1 . . . 292	230/296 (77%)	e−135
	(RIKEN CDNA 2310014B08	1 . . . 296	248/296 (83%)
	GENE) - Mus musculus (Mouse),
	296 aa.
O95484	Claudin-9 - Homo sapiens	9 . . . 206	74/206 (35%)	4e−16
	(Human), 217 aa.	9 . . . 209	101/206 (48%)
Q9Z0S7	Claudin-9 - Mus musculus	9 . . . 206	71/206 (34%)	1e−14
	(Mouse), 217 aa.	9 . . . 209	99/206 (47%)
Q98SR2	CLAUDIN-3 - Gallus gallus	10 . . . 206	64/202 (31%)	1e−13
	(Chicken), 214 aa.	9 . . . 207	99/202 (48%)

[0339] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5E.

TABLE 5E
Domain Analysis of NOV5a
		Identities/
	NOV5a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
PMP22_Claudin	3 . . . 177	40/194 (21%)	0.00018
		108/194 (56%)

Example 6

[0340] The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A.

TABLE 6A
NOV6 Sequence Analysis
	SEQ ID NO:11	2369 bp
NOV6a,	CGGCCGGAGCGCCGAGGCCCGGCCATGGCCACCACCAGCACCACGGGCTCCACCCTGC
CG101231-01
DNA Sequence	TGCAGCCCCTCAGCAACGCCGTGCAGCTGCCCATCGACCAGGTCAACTTTGTAGTGTG
	CCAACTCTTTGCCTTGCTAGCAGCCATTTGGTTTCGAACTTATCTACATTCAAGCAAA
	ACTAGCTCTTTTATAAGACATGTAGTTGCTACCCTTTTGGGCCTTTATCTTGCACTTT
	TTTGCTTTGGATGGTATGCCTTACACTTTCTTGTACAAAGTGGAATTTCCTACTGTAT
	CATGATCATCATAGGAGTGGAGAACATGCACAATTACTGCTTTGTGTTTGCTCTGGGA
	TACCTCACAGTGTGCCAAGTTACTCGAGTCTATATCTTTGACTATGGACAATATTCTG
	CTGATTTTTCAGGCCCAATGATGATCATTACTCAGAAGATCACTAGTTTGGCTTGCGA
	AATTCATGATGGGATGTTTCGGAAGGATGAAGAACTGACTTCCTCACAGAGGGATTTA
	GCTGTAAGGCGCATGCCAAGCTTACTGGAGTATTTGAGTTACAACTGTAACTTCATGG
	GGATCCTGGCAGGCCCACTTTGCTCTTACAAAGACTACATTACTTTCATTGAAGGCAG
	ATCATACCATATCACACAATCTGGTGAAAATGGAAAAGAAGAGACACAGTATGAAAGA
	ACAGAGCCATCTCCAAATAGTGCGGTTGTTCAGAAGCTCTTAGTTTGTGGGCTGTCCT
	TGTTATTTCACTTGACCATCTGTACAACATTACCTGTGGAGTACAACATTGATGAGCA
	TTTTCAAGCTACAGCTTCGTGGCCAACAAAGATTATCTATCTGTATATCTCTCTTTTG
	GCTGCCAGACCCAATACTATTTTGCATGGACGCTAGCTGATGCCATTAATAAATGCTG
	CAGGCTTTGGTTTCAGAGGGTATGACGAAAATGGAGCAGCTCGCTGGGACTTAATTTC
	CAATTTGAGAATTCAACAATAGAGATGTCAACAAGTTTCAAGATGTTTCTTGATAAAT
	TGGAATATTCAGACAGCTCTTTGGCTCAAAAGGGTGTGTTATGAACGAACCTCCTTCA
	GTCCAACTATCCAGACGTTCATTCTCTCTGCCATTTGGCACGGGGTATACCCAGGATA
	TTATCTAACGTTTCTAACAGGGGTGTTAATGACATTAGCAGCAAGAGCTGTAAGAAAT
	AACTTTAGACATTATTTCATTGAACCTTCCCAACTGAAATTATTTTATGATGTTATAA
	CATGGATAGTAACTCAAGTAGCAATAAGTTACACACTTGTGCCATTTGTGCTTCTTTC
	TATAAAACCATCACTCACGTTTTACAGCTCCTGGTATTATTGCCTGCACATTCTTGGT
	ATCTTAGTATTATTGTTGTTGCCAGTAAAAAAAACTCAAAGAAGAAAGAATACACATG
	AAAACATTCAGCTCTCACAATCCAAAAAGTTTGATGAAGGAGAAAATTCTTTGGGACA
	GAACAGTTTTTCTACAACAAACAATGTTTGCAATCAGAATCAAGAAATAGCCTCGAGA
	CATTCATCACTAAAGCAGTGATCGGGAAGGCTCTGAGGGCTGTTTTTTTTTTTTGATG
	TTAACAGAAACCAATCTTAGCACCTTTTCAAGGGGTTTGAGTTTGTTGGAAAAGCAGT
	TAACTGGGGGGAAATGGACAGTTATAGATAAGGAATTTCCTGTACACCAGATTCGAAA
	TGGAGTGAAACAAGCCCTCCCATGCCATGTCCCCGTGGGCCACGCCTTATGTAAGAAT
	ATTTCCATATTTCAGTGGGCACTCCCAACCTCAGCACTTGTCCGTAGGGTCACACGCG
	TGCCCTGTTGCTGAATGTATGTTGCGTATCCCAAGGCACTGAAGAGGTGGAAAAATAA
	TCGTGTCAATCTGGATGATAGAGAGAAATTAACTTTTCCAAATGAATGTCTTGCCTTA
	AACCCTCTATTTCCTAAAATATTGTTCCTAAATGGTATTTTCAAGTGTAATATTGTGA
	GAACGCTACTGCAGTAGTTGATGTTGTGTGCTGTAAAGGATTTTAGGAGGAATTTGAA
	ACAGGATATTTAAGAGTGTGGATATTTTTAAAATGCAATAAACATCTCAGTATTTGAA
	GGGTTTTCTTAAAGTATGTCAAATGACTACAATCCATAGTGAAACTGTAAACAGTAAT
	GGACGCCAAATTATAGGTAGCTGATTTTGCTGGAGAGTTTAATTACCTTGTGCAGTCA
	AAGAGCGCTTCCAGAAGGAATCTCTTAAAACATAATGAGAGGTTTGGTAATGTGATAT
	TTTAAGCTTACTCTTTTTCTTAAAAGAGAGAGGTGACGAAGGAAGGCAG
	ORF Start: ATG at 25		ORF Stop: TGA at 1585
	SEQ ID NO:12	520 aa	MW at 59480.0 kD
NOV6a,	MATTSTTGSTLLQPLSNAVQLPIDQVNFVVCQLFALLAAIWFRTYLHSSKTSSFIRHV
CG101231-01
Protein Sequence	VATLLGLYLALFCFGWYALHFLVQSGISYCIMIIIGVENNHNYCFVFALGYLTVCQVT
	RVYIFDYGQYSADFSGPMMIITQKITSLACEIHDGMFRKDEELTSSQRDLAVRRMPSL
	LEYLSYNCNFMGILAGPLCSYKDYITFIEGRSYHITQSGENGKEETQYERTEPSPNSA
	VVQKLLVCGLSLLFHLTICTTLPVEYNIDEHFQATASWPTKIIYLYISLLAARPKYYF
	AWTLADAINNAAGFGFRGYDENGAARWDLISNLRIQQIEMSTSFKMFLDNWNIQTALW
	LKRVCYERTSFSPTIQTFILSAIWHGVYPGYYLTFLTGVLMTLAARAVRNNFRHYFIE
	PSQLKLFYDVITWIVTQVAISYTVVPFVLLSIKPSLTFYSSWYYCLHILGILVLLLLP
	VKKTQRRKNTHENIQLSQSKKFDEGENSLGQNSFSTTNNVCNQNQEIASRHSSLKQ
SEQ ID NO:13	2270 bp
NOV6b,	CGGCCGGAGCGCCGAGGCCCGGCCATGGCCACCACCAGCACCACGGGCTCCACCCTGC
CG101231-02
DNA Sequence	TGCAGCCCCTCAGCAACGCCGTGCAGCTGCCCATCGACCAGGTCAACTTTGTAGTGTG
	CCAACTCTTTGCCTTGCTAGCAGCCATTTGGTTTCGAACTTATCTACATTCAAGCAAA
	ACTAGCTCTTTTATAAGACATGTAGTTGCTACCCTTTTGGGCCTTTATCTTGCACTTT
	TTTGCTTTGGATGGTATGCCTTACACTTTCTTGTACAAAGTGGAATTTCCTACTGTAT
	CATGATCATCATAGGAGTGGAGAACATGCAGCCAATGATGATCATTACTCAGAAGATC
	ACTAGTTTGGCTTGCGAAATTCATGATGGGATGTTTCGGAAGGATGAAGAACTGACTT
	CCTCACAGAGGGATTTAGCTGTAAGGCGCATGCCAAGCTTACTGGAGTATTTGAGTTA
	CAACTGTAACTTCATGGGGATCCTGGCAGGCCCACTTTGCTCTTACAAAGACTACATT
	ACTTTCATTGAAGGCAGATCATACCATATCACACAATCTGGTGAATGGAAAAGAAAAG
	AGACACAGTATGAAAGAACAGAGCCATCTCCAAATAGTGCGGTTGTTCAGAAGCTCTT
	AGTTTGTGGGCTGTCCTTGTTATTTCACTTGACCATCTGTACAACATTACCTGTGGAG
	TACAACATTGATGAGCATTTTCAAGCTACAGCTTCGTGGCCAACAAAGATTATCTATC
	TGTATATCTCTCTTTTGGCTGCCAGACCCAAATACTATTTTGCATGGACGCTAGCTGA
	TGCCATTAATAATGCTGCAGGCTTTGGTTTCAGAGGGTATGACGAAAATGGAGCAGCT
	CGCTGGGACTTAATTTCCAATTTGAGAATTCAACAATAGAGATGTCAACAAAGTTTCA
	AGATGTTTCTTGATAATTGGAATATTCAGACAGCTCTTTGGCTCAAAAGGGTCTGTTA
	TGAACGAACCTCCTTCAGTCCAACTATCCAGACGTTCATTCTCTCTGCCATTTGGCAC
	GGGGTATACCCAGGATATTATCTAACGTTTCTAACAGGGGTGTTAATGACATTAGCAG
	CAAGAGCTGTAAGAAATAACTTTAGACATTATTTCATTGAACCTTCCCAACTGAAATT
	ATTTTATGATGTTATAACATGGATAGTAACTCAAGTAGCAATAAGTTACACAGTTGTG
	CCATTTGTGCTTCTTTCTATAAAACCATCACTCACGTTTTACAGCTCCTGGTATTATT
	GCCTGCACATTCTTGGTATCTTAGTATTATTGTTGTTGCCAGTAAAAAAAACTCAAAG
	AAGAAAGAATACACATGAAAACATTCAGCTCTCACAATCCAAAAAGTTTGATGAAGGA
	GAAATTCTTTGGGACAGAACAGTTTTTCTACAACAAACAATGTTTGCAAATCAGAATC
	AAGAAATAGCCTCGAGACATTCATCACTAAAGCAGTGATCGGGAAGGCTCTGAGGGCT
	GTTTTTTTTTTTTGATGTTAACAGAAACCAATCTTAGCACCTTTTCAAGGGGTTTGAG
	TTTGTTGGAAAAGCAGTTAACTGGGGGGAAATGGACAGTTATAGATAAGGAATTTCCT
	GTACACCAGATTGGAAATGGAGTGAAACAAGCCCTCCCATGCCATGTCCCCGTGGGCC
	ACGCCTTATGTAAGAATATTTCCATATTTCAGTGGGCACTCCCAACCTCAGCACTTGT
	CCGTAGGGTCACACGCGTGCCCTGTTGCTGAATGTATGTTGCGTATCCCAAGGCACTG
	AAGAGGTGGAAAATAATCGTGTCAATCTGGATGATAGAGAGAAATTAACTTTTCCAAA
	ATGAATGTCTTGCCTTAAACCCTCTATTTCCTAAAATATTGTTCCTA3ATGGTATTTT
	CAAGTGTAATATTGTGAGAACGCTACTGCAGTAGTTGATGTTGTGTGCTGTAAAGGAT
	TTTAGGAGGAATTTGAAACAGGATATTTAAGAGTGTGGATATTTTTAAAATGCAATAA
	ACATCTCAGTATTTGAAGGGTTTTCTTAAAGTATGTCAAATGACTACAATCCATAGTG
	AAACTGTAAACAGTAATGGACGCCAAATTATAGGTAGCTGATTTTGCTGGAGAGTTTA
	ATTACCTTGTGCAGTCAAAGAGCGCTTCCAGAAGGAATCTCTTAAAACATAATGAGAG
	GTTTGGTAATGTGATATTTTAAGCTTACTCTTTTTCTTAAAAGAGAGAGGTGACGAAG
	GAAGGCAG
	ORF Start: ATG at 25		ORF Stop: TGA at 1486
	SEQ ID NO:14	487 aa	MW at 55677.7 kD
NOV6b,	MATTSTTGSTLLQPLSNAVQLPIDQVNFVVCQLFALLAAIWFRTYLHSSKTSSFIRHV
CG101231-02
Protein Sequence	VATLLGLYLALFCFGWYALHFLVQSGISYCIMIIIGVENMQPMMIITQKITSLACEIH
	DGMFRKDEELTSSQRDLAVRRMPSLLEYLSYNCNFMGILAGPLCSYKDYITFIEGRSY
	HITQSGENGKEETQYERTEPSPNSAVVQKLLVCGLSLLFHLTICTTLPVEYNIDEHFQ
	ATASWPTKIIYLYISLLAARPKYYFAWTLALAINNAAGFGFRGYDENGAAAWDLISNL
	RIQQIEMSTSFKMFLDNANIQTALWLKRVCYERTSFSPTIQTFILSAIWHGVYPGYYL
	TFLTGVLMTLAARAVRNNFRHYFIEPSQLKLFYDVITWIVTQVAISYTVVPFVLLSIK
	PSLTFYSSWYYCLHILGILVLLLLPVKKTQRRKNTHENIQLSQSKKFDEGENSLGQNS
	FSTTNNVCNQNQEASRHSSLKQ

[0341] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 6B.

TABLE 6B
Comparison of NOV6a against NOV6b.
	NOV6a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV6b	1 . . . 520	474/520 (91%)
	1 . . . 487	474/520 (91%)

[0342] Further analysis of the NOV6a protein yielded the following properties shown in Table 6C.

TABLE 6C
Protein Sequence Properties NOV6a
PSort     0.6000 probability located in plasma membrane;
analysis: 0.4000 probability located in Golgi body;
          0.3406 probability located in mitochondrial
          intermembrane space;
          0.3384 probability located in mitochondrial inner membrane
SignalP   Cleavage site between residues 44 and 45
analysis:

[0343] A search of the NOV6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6D.

TABLE 6D
Geneseq Results for NOV6a
		NOV6a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAG81345	Human AFP protein sequence SEQ	98 . . . 520	419/423 (99%)	0.0
	ID NO: 208 - Homo sapiens, 423 aa.	1 . . . 423	421/423 (99%)
	[WO200129221-A2, 26-APR-2001]
AAB93797	Human protein sequence SEQ ID	102 . . . 520	416/419 (99%)	0.0
	NO: 13560 - Homo sapiens, 432 aa.	14 . . . 432	419/419 (99%)
	[EP1074617-A2, 07-FEB-2001]
AAM93974	Human stomach cancer expressed	102 . . . 520	416/419 (99%)	0.0
	polypeptide SEQ ID NO: 17 - Homo	14 . . . 432	419/419 (99%)
	sapiens, 432 aa. [WO200109317-
	A1, 08-FEB-2001]
ABG04835	Novel human diagnostic protein	50 . . . 297	243/248 (97%)	e−143
	#4826 - Homo sapiens, 371 aa.	23 . . . 270	246/248 (98%)
	[WO200175067-A2, 11-OCT-2001]
ABG04835	Novel human diagnostic protein	50 . . . 297	243/248 (97%)	e−143
	#4826 - Homo sapiens, 371 aa.	23 . . . 270	246/248 (98%)
	[WO200175067-A2, 11-OCT-2001]

[0344] In a BLAST search of public sequence databases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6E.

TABLE 6E
Public BLASTP Results for NOV6a
		NOV6a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
AAH25429	SIMILAR TO RIKEN CDNA	1 . . . 520	451/520 (86%)	0.0
	2810049G06 GENE - Mus	1 . . . 519	479/520 (91%)
	Musculus (Mouse), 519 aa.
CAC38595	SEQUENCE 207 FROM	98 . . . 520	419/423 (99%)	0.0
	PATENT WO0129221 - Homo	1 . . . 423	421/423 (99%)
	sapiens (Human), 423 aa.
AAH25020	RIKEN CDNA 2810049G06	1 . . . 520	422/520 (81%)	0.0
	GENE - Mus musculus (Mouse),	1 . . . 487	449/520 (86%)
	487 aa.
Q9CZ73	2810049G06RIK PROTEIN -	1 . . . 520	421/520 (80%)	0.0
	Mus musculus (Mouse), 487 aa.	1 . . . 487	448/520 (85%)
Q96KY4	SIMILAR TO RIKEN CDNA	171 . . . 520	348/350 (99%)	0.0
	2810049G06 GENE - Homo	1 . . . 350	350/350 (99%)
	sapiens (Human), 350 aa.

[0345] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6F.

TABLE 6F
Domain Analysis of NOV6a
		Identities/
	NOV6a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Adeno_Penton_B	204 . . . 222	8/20 (40%)	0.54
		17/20 (85%)
MBOAT	148 . . . 442	108/334 (32%)	4.1e−89
		225/334 (67%)

Example 7

[0346] The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A.

TABLE 7A
NOV7 Sequence Analysis
	SEQ ID NO:15	537 bp
NOV7a,	ATTAGCAACGGCTCATGATGAACTCAATCAAAGGGGGCTTGACCAGCATCTCAGGTCT
CG101362-01
DNA Sequence	ACTCTATGTTTTCCAGTGCCCATCAGTGCCAAGGGTATTGATTAGCCTATCCGGGACA
	AAGAGAGAAGAAAGAGTGAGACACCACCACTAAAAGGGCTGCAGGTGGATACCGCCTC
	CCTCAAGCTGGAAAAAGATTAGAAAGATGGTGAAAACAGGAAGACCTTCCTCATCCCA
	CTATCAGGAAGATGAGGAAAGAGATCAGGAGGATCACAGGTGGAGAGGAGAAGAGGAC
	CATGCTCGATCCTCTCTGGTAATAGGCCTGAGATTCCCTCTCGTACTGGGTGATACAC
	ATCTGCTCCCAGTGTTCCATCCTCCAGGCTTCGGGCGCTTCTTGCAGAGGCCCAGGTC
	ACTCCATGTGGCCACAAAGAGAACCAGCATCCAGCAGCCATGGTTCGCCATAATGACT
	GCTCTGCCTCGGTCGTGAGGAGAGGAGAAGCTCGCGGCGCCGCGGCTGTCAGCGACTG
	GCTCGGAGGACAGGC
	ORF Start: ATG at 201		ORF Stop: TGA at 480
	SEQ ID NO:16	93 aa	MW at 10769.1 kD
NOV7a,	MVKTGRPSSSHYQEDEERDQEDHRWRGEEDHARSSLVIGLRFPLVLGDTHLLPVFHPP
CG101362-01
Protein Sequence	GFGRFLQRPRSLHVATKRTSIQQPRFAIMTALPRS

[0347] Further analysis of the NOV7a protein yielded the following properties shown in Table 7B.

TABLE 7B
Protein Sequence Properties NOV7a
PSort     0.6400 probability located in microbody (peroxisome);
analysis: 0.4500 probability located in cytoplasm;
          0.2288 probability located in lysosome (lumen);
          0.1000 probability located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0348] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7C.

TABLE 7C
Geneseq Results for NOV7a
			Identities/
		NOV7a	Similarities
		Residues/	for the
Geneseq	Protein/Organism/Length [Patent #,	Match	Matched	Expect
Identifier	Date]	Residues	Region	Value
AAY19678	SEQ ID NO 396 from WO9922243 -	1 . . . 30	14/30 (46%)	0.94
	Homo sapiens, 133 aa. [WO9922243-	63 . . . 91	19/30 (62%)
	A1, 06-MAY-1999]
AAB92467	Human protein sequence SEQ ID	2 . . . 90	24/90 (26%)	1.2
	NO: 10527 - Homo sapiens, 563 aa.	318 . . . 398	41/90 (44%)
	[EP1074617-A2, 07-FEB-2001]
AAU16292	Human novel secreted protein, Seq ID	2 . . . 90	24/90 (26%)	1.2
	1245 - Homo sapiens, 564 aa.	319 . . . 399	41/90 (44%)
	[WO200155322-A2, 02-AUG-2001]
ABB50224	Human transcription factor TRFX-75 -	2 . . . 90	24/90 (26%)	1.2
	Homo sapiens, 596 aa.	351 . . . 431	41/90 (44%)
	[WO200172777-A2, 04-OCT-2001]
AAM33060	Peptide #7097 encoded by probe for	5 . . . 30	13/26 (50%)	1.6
	measuring placental gene expression -	1 . . . 25	18/26 (69%)
	Homo sapiens, 49 aa.
	[WO200157272-A2, 09-AUG-2001]

[0349] In a BLAST search of public sequence databases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7D.

TABLE 7D
Public BLASTP Results for NOV7a
			Identities/
		NOV7a	Similarities
Protein		Residues/	for the
Accession		Match	Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9D3A0	6330414C15RIK PROTEIN - Mus	1 . . . 30	14/30 (46%)	2.2
	musculus (Mouse), 150 aa.	51 . . . 79	19/30 (62%)
Q9Y269	Protein HSPC020 - Homo sapiens	1 . . . 30	14/30 (46%)	2.2
	(Human), and, 121 aa.	51 . . . 79	19/30 (62%)
Q9UKD0	DNA BINDING PROTEIN P96PIF	2 . . . 90	24/90 (26%)	2.9
	(GLUCOCORTICOID	318 . . . 398	41/90 (44%)
	MODULATORY ELEMENT
	BINDING PROTEIN 1) - Homo
	sapiens (Human), 563 aa.
Q9NWH1	HYPOTHETICAL 61.4 KDA	2 . . . 90	24/90 (26%)	2.9
	PROTEIN - Homo sapiens (Human),	318 . . . 398	41/90 (44%)
	563 aa.
Q9Y692	GLUCOCORTICOID	2 . . . 90	24/90 (26%)	3.8
	MODULATORY ELEMENT	328 . . . 408	40/90 (43%)
	BINDING PROTEIN-1 - Homo
	sapiens (Human), 573 aa.

Example 8

[0350] The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A.

TABLE 8A
NOV8 Sequence Analysis
	SEQ ID NO:17	3653 bp
NOV8a,	CGGGATGCCCGGCTTGCTGAATTGGATCACGGGGGCAGCCCTGCCCCTCACCGCGTCT
CG101458-01
DNA Sequence	GATGTTACCTCCTGTGTCAGCGGTTATGCCCTGGGCCTAACTGCCTCCCTCACCTATG
	GCAACCTGGATGCCCAGCCCTTCCAGGGTCTCTTCGTGTACCCCCTGGATGAGTGCAC
	CACGGTGATCGGCTTTGAGGCAGTCATTGCCGACCGTGTCGTGACAGTACAGATCAAG
	GACAAAGCCAAGCTGGAGAGCGGCCACTTCGATGCCTCCCATGTTCGATCCCCAACAG
	TCACAGGTAAGGAGACCAGAAGGGCTGCCGCGGGACCTGGGAAGGTGACCTTGGACGA
	GGATTTGGAGCGGATCCTGTTCGTGGCCAACCTGGGGACCATTGCCCCCATGGAGAAT
	GTCACCATCTTCATCAGCACCTCCTCGGAGCTCCCAACGCTGCCCAGCGGGGCTGTGA
	GGGTCCTTCTGCCTGCTGTCTGTGCCCCAACCGTGCCCCAGTTCTGCACCAAGAGCAC
	TGGCACCTCCAACCAACAGGCCCAGGGGAAAGACAGGCACTGCTTCGGTGCCTGGGCC
	CCGGGCTCCTGGAATAAGTTGTGCCTGGCGACTCTCCTGAACACCGAAGTGTCCAACC
	CCATGGAGTATGAGTTCAACTTCCAGCTGGAGATCCGTGGGCCATGTCTGCTCGCAGG
	TGTGGAGAGTCCCACTCATGAGATTCGTGCCGACGCCGCCCCATCTGCCCGCTCGGCC
	AAGAGCATCATCATCACCTTGGCCAACAAGCACACCTTTGACCGGCCTGTGGAGATCC
	TCATCCACCCCAGCGAGCCCCATATGCCCCATGTCCTGATAGAGAAAGGGGACATGAC
	CCTGGGAGAGTTTGACCAGCACTTGAAGGGAAGAACAGATTTCATTAAAGGGATGAAG
	AAGAAGAGCAGAGCAGAGCGGAAGACAGAAATCATTCGAAAACGCCTCCACAAAGACA
	TTCCCCACCACTCCGTCATCATGCTCAACTTCTGTCCCGACCTCCAGTCAGTCCAGCC
	GTGCCTGAGAAAGGCCCACGGGGAGTTCATCTTCCTCATTGACAGGAGCAGCAGCATG
	AGCGGGATCAGCATGCACCGAGTCAAGGATGCCATGTTGGTGGCCCTTAAGAGCCTCA
	TGCCAGCCTGCCTCTTCAATATCATTGGGTTTGGATCCACATTTAAGAGCCTTTTTCC
	TTCCAGCCAGACCTACAGTGAGGACAGCTTGGCCATGGCTTGTGATGACATCCAGAGA
	ATGAAGGCCQACATGGGTGGGACCAACATCCTTTCCCCTCTCAAGTGGGTCATCAGGC
	AGCCAGTGCACCGAGGCCACCCGCGGCTCCTCTTCGTGATCACAGATGGCGCTGTCAA
	CAACACAGGGAAAGGTGCTGGAGCTGGTGCGAATCACGCCTTCTCCACCAGGTGCTAT
	AGCTTTGGAATTGGACCCAACGTCTGCCACAGACTGGTGAAAGGACTGGCATCTGTGT
	CCGAGGGCAGTGCTGAGCTCCTGATGGAGGGGGAGCGGCTGCAACCCAAGATGGTCAA
	ATCCTTGAAGAAGGCCATGGCCCCAGTCCTGAGCGATGTGACTGTGGAGTGGATCTTC
	CCTGAGACCACTGAGGTCCTGGTCTCACCCGTCAGCGCCAGCTCCCTCTTCCCTGGAG
	AACGGCTGGTGGGGTATGGCATTGTATGTGATGCTTCTTTGCACATCTCCAATCCCAG
	ATCTGACAAGAGGCGCCGGTACAGCATGCTGCACTCTCAGGAGTCTGGCAGCTCTGTC
	TTCTACCACTCTCAGGATGACGGACCCGGGCTGGAAGGTGGAGACTGTGCCAAGAACT
	CGGGGGCACCCTTCATCCTAGGGCAGGCCAAAAATGCCCGGCTAGCCAGCGGAGACTC
	TACCACCAAGCACGGTCTGAACCTCTCTCAGCGACGGAGGGCATACAGCACCAACCAG
	ATCACCAATCACAAGCCCCTCCCAAGAGCCACCATGGCAAGTGACCCCATGCCAGCTG
	CCAAGAGATACCCACTGCGGAAAGCCAGGCTGCAGGACCTCACCAACCAGACCAGCCT
	GGATGTCCAGCGGTGGCAGATTGATTTGCAGGTATTGCTGAACAGTGGTCAGGACCTG
	AACCAGGGCCCCAAACTCCGTGGCCCAGGGGCCCGAAGGCCCTCTCTGCTGCCCCAAG
	GCTGCCAGCCCTTCCTGCCCTGGGGCCAGGAGACCCAGGCCTGGAGCCCTGTGAGAGA
	GCGGACTTCTGACAGCCGAAGCCCTGGAGATCTGCCCGCAGAGCCGTCCCACCATCCC
	TCTGCCTTCGAGACAGAGACGTCCTCGGACTGGGACCCCCCAGCCGAGTCCCAGGAGC
	GAGCCAGTCCCAGCAGGCCCGCCACCCCGGCCCCGGTGCTGGGCAAGGCCCTGGTCAA
	AGGCCTGCACGACAGCCAACGCCTGCAGTGGGAGGTGAGCTTCGAGCTGGGGACCCCT
	GGACCGGAGCGGGGCGGCGCGCAGGATGCCGACCTATGGACCGAGACCTTCCACCACC
	TGGCGGCCCGCGCCATCATCCGCGACTTCGAGCAGCTGGCGGAGCGCGAGGGCGAGAT
	CGAGCAGGGTTCCAACCGCCGCTACCAAGTGAGCGCCTTGCACACCAGCAAGGCCTGC
	AACATCATTAGCAAATACACAGCCTTCGTGCCTGTGGACGTGAGCAAGAGCCGGTACC
	TGCCCACCGTGGTGGAGTACCCCAACTCTGGTCGTATGCTTGGCTCTCGGGCCCTGGC
	CCAACAGTGGAGGCGCACCTCTTCTGGCTTTGGAAGGCCGCAGACGATGCTTGGAGAA
	GATTCGGCACCAGGAAATGGTAAATTTCAGGTCCTAGACATGGAGGCAAGTCCCACTG
	CTCTCTTCAGCGAGGCCAGGTCCCCCGGCCGCGAGAAGCACGGTGCTTCTGAAGGTCC
	CCAGCGCAGCCTGGCTACAAATACTCTTTCTTCCATGAAGGCCTCAGAGAATCTCTTT
	GGATCCAGGCTAAATCTCAACAAGTCCAGGCTACTGACGCGAGCAGCCAAGGGCTTCC
	TGAGCAAGCCACTGATCAAAGCTGTGGAGTCGACCTCCGGGAACCAGAGCTTCGACTA
	CATACCTCTGGTGTCTCTGCAGCTGGCCTCCGGAGCCTTCCTGCTCAACGAAGCCTTC
	TGTGAGGCCACGCACATCCCCATGGAGAAGCTCAAGTGGACGTCCCCCTTCACCTGCC
	ATCGAGTGTCCCTCACCACCCGCCCGTCTGAGTCCAAGACCCCGAGTCCCCAGCTGTG
	CACCAGCTCCCCGCCTAGGCACCCGTCCTGTGACAGCTTCTCCCTGGAGCCTCTGGCC
	AAGGGCAAGCTGGGCCTGGAGCCGAGGGCAGTGGTGGAGCACACTGGGAAGCTGTGGG
	CCACGGTGGTGGGGCTGGCATGGCTGGAGCACAGTTCGGCCTCCTACTTCACTGAGTG
	GGAGTTGGTGGCTGCCAAGGCCAACTCATGGCTGGAGCAGCAGGAAGTACCCGAGGGC
	CGCACGCAGGGCACACTCAAGGCCGCTGCCCGCCAGCTGTTTGTGCTTCTGCGGCACT
	GGGATGAGAATCTCGAGTTCAATATGCTCTGCTATAACCCGAATTATGTGTAGTTGA
	ORF Start: ATG at 5		ORF Stop: TAG at 3647
	SEQ ID NO:18	1213 aa	MW at 133118.0 kd
NOV8a,	MPGLLNWITGAALPLTASDVTSCVSGYALGLTASLTYGNLEAQPFQGLFVYPLDECTT
CG101458-01
Protein Sequence	VIGFEAVIADRVVTVQIKDKAKLESGHFDASHVRSPTVTGKETRRAAAGPGKVTLDED
	LERILFVANLGTIAPMENVTIFISTSSELPTLPSGAVRVLLPAVCAPTVPQFCTKSTG
	TSNQQAQGKDRHCFGAWAPGSWNKLCLATLLNTEVSNPMEYEFNFQLEIRGPCLLAGV
	ESPTHEIRADAAPSARSAKSIIITLANKHTFDRPVEILIHPSEPHMPHVLIEKGDMTL
	GEFDQHLKGRTDFIKGMKKKSRAERKTEIIRKRLHKDIPHHSVIMLNFCPDLQSVQPC
	LRKAHGEFIFLIDRSSSMSGISMHRVKDAMLVALKSLMPACLFNIIGFGSTFKSLFPS
	SQTYSEDSLAMACDDIQRMKADMGGTNILSPLKNVIRQPVHRGHPRLLFVITDGAVNN
	TGKVLELVRNHAFSTRCYSFGIGPNVCHRLVKGLASVSEGSAELLMEGERLQPKMVKS
	LKKAIAPVLSDVTVEWIFPETTEVLVSPVSASSLFPGERLVGYGIVCDASLHISNPRS
	DKRRRYSMLHSQESGSSVFYHSQDDGPGLEGGDCAKNSCAPFILGQAKNARLASGDST
	TKHGLNLSQRRRAYSTNQITNHKPLRRATMASDPMPAAKRYPLRKARLQDLTNQTSLD
	VQRWQIDLQVLLNSGQDLNQGPKLRGPGARRPSLLPQGCQPFLPWGQETQAWSPVRER
	TSDSRSPGDLPAEPSHHPSAFETETSSDWDPPAESQERASPSRPATPAPVLGKALVKG
	LHDSQRLQWEVSFELGTPGPERGGAQDADLWSETFHHLAARAIIRDFEQLAEREGEIE
	QGSNRRYQVSALHTSKACNIISKYTAFVPVDVSKSRYLPTVVEYPNSGRMLGSRALAQ
	QWRGTSSGFGRPQTMLGEDSAPGNGKFQVLDMEASPTALFSEARSPGREKHGASEGPQ
	RSLATNTLSSMKASENLFGSRLNLNKSRLLTRAAKGFLSKPLIKAVESTSGNQSFDYI
	PLVSLQLASGAFLLNEAFCEATHIPMEKLKWTSPFTCHRVSLTTRPSESKTPSPQLCT
	SSPPMPSCDSFSLEPLAKGKLGLEPPAVVEHTGKLWATVVNGLAWLEHSSASYFTEWE
	LVAAKANSWLEQQEVPEGRTQGTLKAAARQLFVLLRHWDENLEFNMLCYNPNYV

[0351] Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.

TABLE 8B
Protein Sequence Properties NOV8a
PSort     0.8700 probability located in nucleus; 0.8500 probability
analysis: located in endoplasmic reticulum (membrane);
          0.7900 probability located in plasma membrane;
          0.3325 probability located in microbody (peroxisome)
SignalP   Cleavage site between residues 19 and 20
analysis:

[0352] A search of the NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8C.

TABLE 8C
Geneseq Results for NOV8a
		NOV8a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB82047	Human mast cell surface antigen -	13 . . . 565	168/565 (29%)	2e−59
	Homo sapiens, 786 aa.	15 . . . 500	269/565 (46%)
	[JP2001025388-A, 30-JAN-2001]
AAY82530	Human neurotransmitter associated	1034 . . . 1211	82/194 (42%)	1e−32
	protein sequence SEQ ID NO: 6 -	16 . . . 207	105/194 (53%)
	Homo sapiens, 210 aa.
	[WO200012685-A2, 09-MAR-2000]
AAU33242	Novel human secreted protein	36 . . . 568	120/537 (22%)	4e−23
	#3733 - Homo sapiens, 1730 aa.	650 . . . 1096	214/537 (39%)
	[WO200179449-A2, 25-OCT-2001]
AAB51022	Human minor vault protein p193 -	36 . . . 568	120/537 (22%)	6e−23
	Homo sapiens, 1724 aa.	644 . . . 1090	214/537 (39%)
	[US6156879-A, 05-DEC-2000]
AAY54373	cDNA sequence encoding the	36 . . . 568	120/537 (22%)	6e−23
	human minor vault protein p193 -	644 . . . 1090	214/537 (39%)
	Homo sapiens, 1724 aa.
	[WO9962547-A1, 09-DEC-1999]

[0353] 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 8D.

TABLE 8D
Public BLASTP Results for NOV8a
		NOV8a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9CUE8	4931403E03RIK PROTEIN - Mus	1 . . . 1208	883/1218 (72%)	0.0
	musculus (Mouse), 1209 aa	1 . . . 1209	1012/1218 (82%)
	(fragment).
Q96M71	CDNA FLJ32784 FIS, CLONE	588 . . . 953	362/369 (98%)	0.0
	TESTI2002245 - Homo sapiens	1 . . . 367	362/369 (98%)
	(Human), 424 aa.
Q9BVH8	HYPOTHETICAL 106.2 KDA	274 . . . 1211	311/1047 (29%)	e−106
	PROTEIN - Homo sapiens	32 . . . 998	467/1047 (43%)
	(Human), 1001 aa (fragment).
O75668	DJ745E8.1 (BREAST CANCER	417 . . . 564	148/148 (100%)	4e−80
	SUPPRESSOR CANDIDATE 1	1 . . . 148	148/148 (100%)
	(BCSC-1) LIKE) - Homo sapiens
	(Human), 148 aa (fragment).
Q9CTV9	5830475I06RIK PROTEIN - Mus	13 . . . 565	165/567 (29%)	5e−57
	musculus (Mouse), 565 aa	15 . . . 500	259/567 (45%)
	(fragment).

[0354] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8E.

TABLE 8E
Domain Analysis of NOV8a
		Identities/
		Similarities
		for the Matched	Expect
Pfam Domain	NOV8a Match Region	Region	Value
vwa	355 . . . 523	37/203 (18%)	0.021
		107/203 (53%)

Example 9

[0355] The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A.

TABLE 9A
NOV9 Sequence Analysis
	SEQ ID NO:19	868 bp
NOV9a,	CGTTTTCTTCTACAATGTCTGAAGAAGTGACCTACGCGACACTCACATTTCAGGATTC
CG101475-01
DNA Sequence	TGCTGGAGCAAGGAATAACCGAGTATGGAAATAACCTAAGAAAAGAGGTCATCCAGCT
	CCATCTCCCATTTGGCGTCATGCTGCTCTGGGTCTGGTAACTCTTTGCCTGATGTTGC
	TGATTGGGCTGGTGACATTGGGGATGATGTGTTTGCAGATATCTAATGACATTAACTC
	AGATTCAGAGAAATTGAGTCAACTTCAGAAAACCATCCAACAGCAGCAGGATAACTTA
	TCCCAGCAACTGGGCAACTCCAACAACTTGTCCATGGAGGAGGAATTTCTCAAGTCAC
	AGATCTCCAGTGTACTGAAGAGGCAGGAACAAATGGCCATCAAACTGTGCCAAGAGCT
	AATCATTCATTTTTCAGACCACAGATGTAATCCATGTCCTAAGATGTGGCAATGGTAC
	CAAAATAGTTGCTACTATTTTACAACAAATGAGGAGAAAACCTGGGCTAACAGTAGAA
	AGGACTGCATAGACAAAGAACTCCACCCTAGTGAAGATAGACAGTTTGGAAGAAAGGA
	TTTTCTTATGTCACAGCCATTACTCATGTTTTCGTTCTTTTGGCTGGGATTATCATGG
	GACTCCTCTGGCAGAAGTTGGTTCTGGGAAGATGGCTCTGTTCCCTCTCCATCCTTGA
	GTACTAAAGAACTTGACCAGATCAATGGATCCAAAGGATGTGCTTATTTTCAAAAAGG
	AAATATTTATATTTCTCGCTGTAGTGCTGAAATTTTTTGGATTTGCGAGAAGACAGCT
	GCCCCAGTGAGACTGAGGATTTGGATTAGTATGCTTCTTCCAAATTCTCCAAGAA
	ORF Start: ATG at 15		ORF Stop: TAG at 840
	SEQ ID NO:20	275 aa	MW at 31470.4 kD
NOV9a,	MSEEVTYATLTFQDSAGARNNRDGNNLRKRGHPAPSPIWRHAALGLVTLCLMLLIGLV
CG101475-01
Protein Sequence	TLGMMCLQISNDINSDSEKLSQLQKTIQQQQDNLSQQLGNSNNLSMEEEFLKSQISSV
	LKRQEQMAIKLCQELIIHFSDHRCNPCPKMWQWYQNSCYYFTTNEEKTWANSRKDCID
	KNSTLVKIDSLEEKDFLMSQPLLMFSFFWLGLSWDSSGRSWFWEDGSVPSPSLSTKEL
	DQINGSKGCAYFQKGNIYISRCSAEIFWICEKTAAPVKTEDLD
	SEQ ID NO:21	819 bp
NOV9b,	ACACTCACATTTCAGGATTCTGCTGGAGCAAGGAATAACCGAGATGGAAATAACCTAA
CG101475-02
DNA Sequence	GAAAAAGAGGGCATCCAGCTCCATCTCCCATTTGGCGTCATGCTGCTCTGGGTCTGGT
	AACTCTTTGCCTGATGTTGCTGATTGGGCTGGTGACGTTGGGGATGATGTTTTTGCAG
	ATATCTAATGACATTAACTCAGATTCAGAGAAATTGAGTCAACTTCAGAAAACCATCC
	AACAGCAGCAGGATAACTTATCCCAGCAACTGGGCAACTCCAACAACTTGTCCATGGA
	GGAGGAATTTCTCAGTCACAGATCTCCAGTGTACTGAAGAAGGCAGGAACAAATGGCC
	ATCAAACTGTGCCAAGAGCTAATCATTCATACTTCAGACCACAGATGTAATCCATGTC
	CTAAGATGTGGCAATGGTACCAAAATAGTTGCTACTATTTTACAACAAATGAGGAGAA
	AACCTGGGCTAACAGTAGAAAGGACTGCATAGACAAGAACTCCACCCTAGTGAAGATA
	GACAGTTTGGAAGAAAAGGATTTTCTTATGTCACAGCCATTACTCATGTTTTCGTTCT
	TTTGGCTGGGATTATCATGGGACTCCTCTGGCAGAAGTTGCTTCTGGGAAGATGGCTC
	TGTTCCCTCTCCATCCTTATTTAGTACTAAAGAACTTGACCAGATCAATGGATCCAAA
	GGATGTGCTTATTTTCAAAGGAAAAATATTTATATTTCTCGCTGTAGTGCTGAAATTT
	TTTGGATTTGCGAGAAAGACAGCTGCCCCAGTGAAGACTGAGGATTTGGATTAGAGGG
	CGATTCC
	ORF Start: at 1		ORF Stop: TAG at 805
	SEQ ID NO: 22	268 aa	MW at 30704.5 kD
NOV9b,	TLTFQDSAGARNNRDGNNLRKRGHPAPSPIWRHAALGLVTLCLMLLIGLVTLGMMFLQ
CG101475-02
Protein Sequence	ISNDINSDSEKLSQLQKTIQQQQDNLSQQLGNSNNLSMEEEFLKSQISSVLKRQEQMA
	IKLCQELIIHTSDHRCNPCPKMWQWYQNSCYYFTTNEEKTWANSRKDCIDKNSTLVKI
	DSLEEKDFLMSQPLLMFSFFWLGLSWDSSGRSWFWEDGSVPSPSLFSTKELDQINGSK
	GCAYFQKGNIYISRCSAEIFWICEKTAAPVKTEDLD

[0356] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 9B.

TABLE 9B
Comparison of NOV9a against NOV9b.
		Identities/
	NOV9a Residues/	Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV9b	9 . . . 275	241/268 (89%)
	1 . . . 268	241/268 (89%)

[0357] Further analysis of the NOV9a protein yielded the following properties shown in Table 9C.

TABLE 9C
Protein Sequence Properties NOV9a
PSort     0.7900 probability located in plasma membrane; 0.3000 probability located in
analysis: Golgi body; 0.2000 probability located in endoplasmic reticulum (membrane);
          0.1000 probability located in mitochondrial inner membrane
SignalP   Cleavage site between residues 62 and 63
analysis:

[0358] 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/
	Protein/Organism/	Residues/	Similarities for
Geneseq	Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAU29320	Human PRO polypeptide sequence	1 . . . 227	224/227 (98%)	e−131
	#297 - Homo sapiens, 232 aa.	1 . . . 227	225/227 (98%)
	[WO200168848-A2, 20 SEP. 2001]
AAM79324	Human protein SEQ ID NO 2970 -	1 . . . 270	91/270 (33%)	3e−37
	Homo sapiens, 289 aa.	25 . . . 280	147/270 (53%)
	[WO200157190-A2, 09 AUG.
	2001]
ABB11776	Human macrophage Ag homologue,	1 . . . 270	91/270 (33%)	3e−37
	SEQ ID NO: 2146 - Homo sapiens,	25 . . . 280	147/270 (53%)
	289 aa. [WO200157188-A2, 09
	AUG. 2001]
AAM78340	Human protein SEQ ID NO 1002 -	1 . . . 270	88/270 (32%)	1e−35
	Homo sapiens, 265 aa.	1 . . . 256	147/270 (53%)
	[WO200157190-A2, 09 AUG.
	2001]
AAY02283	Secreted protein clone br342_11	1 . . . 270	88/270 (32%)	1e−35
	polypeptide sequence - Homo	1 . . . 256	147/270 (53%)
	sapiens, 265 aa. [WO9918127-A1,
	15 APR. 1999]

[0359] 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 for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9D403	4933425B16RIK PROTEIN - Mus	1 . . . 275	197/276 (71%)	e−113
	musculus (Mouse), 275 aa.	1 . . . 275	227/276 (81%)
AAL95693	C-TYPE LECTIN PROTEIN	1 . . . 270	88/270 (32%)	2e−35
	CLL-1 - Homo sapiens (Human),	1 . . . 256	147/270 (53%)
	265 aa.
Q9NZH3	C-TYPE LECTIN-LIKE	28 . . . 274	83/249 (33%)	5e−33
	RECEPTOR-1 - Homo sapiens	36 . . . 269	131/249 (52%)
	(Human), 280 aa.
Q9XTA8	LECTIN-LIKE OXIDIZED LDL	36 . . . 272	79/247 (31%)	5e−27
	RECEPTOR - Oryctolagus	36 . . . 278	124/247 (49%)
	cuniculus (Rabbit), 278 aa.
P78380	LECTIN-LIKE OXIDIZED LDL	36 . . . 266	79/245 (32%)	3e−24
	RECEPTOR - Homo sapiens	32 . . . 268	124/245 (50%)
	(Human), 273 aa.

[0360] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9F.

TABLE 9F
Domain Analysis of NOV9a
		Identities/
		Similarities for	Expect
Pfam Domain	NOV9a Match Region	the Matched Region	Value
lectin_c	161 . . . 264	29/125 (23%)	7.4e−06
		61/125 (49%)

Example 10

[0361] The NOV 10 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 10A.

TABLE 10A
NOV10 Sequence Analysis
	SEQ ID NO: 23	516 bp
NOV10a,	CACTGCGCATGCTATTTGGGCGCCCACCTCAGTGCACATGTTCACTGGGCGTCTTCTA
CG101772-01	CTCTACCCCTTCGCCCTCGTGGGGGTGTGAGGGTCGCGTTCCTGCTGTCTGGACTTTT
DNA Sequence	TCTGTCCCACTGAGACGCAATGTATCGATAACAAAACTTTTTATCTGCACACACACAC
	ACCACCAACTGAAAGTCGGGATCCTGCACCTGGTCAGGAGAGAGAAGAAGATCAGGGT
	GCAGCTGAGACTCAATGCCTGACCTGGAAGCTGATCTCCAGGAGCTGTCTCAGTCAAA
	GACTGGGGGTGAATGTGGAAATGAAGATTCTGCCAAAATCAGAACAATTTAAAATGCC
	AGAAGGAGGTATGCTATCCATTATTATGTGCTTTCTGTTTTCCACAATATTATACTTT
	TGATAATAAAAGAGAACATTACTATCCCTTTAAAATCAGAGTTCAAATGCAG
	ORF Start: ATG at 9	ORF Stop: TGA at 465
	SEQ ID NO: 24	152 aa	MW at 17265.6kD
NOV10a,	MLFGRPPQCTCSLGVFYSTPSPSWGCEGRVPAVWTFSVPLRRNVSITKLFICTHTHTH
CG101772-01	THPWFQEPGDEEPQQEEPPTESRDPAPGQEREEDQGAAETQCLTWKLISRSCLSQRLG
Protein Sequence	VNVEMKILPKSEQFKMPEGGMLSIIMCFLFSTILYF

[0362] Further analysis of the NOV10a protein yielded the following properties shown in Table 10B.

TABLE 10B
Protein Sequence Properties NOV10a
PSort     0.9190 probability located in plasma membrane; 0.2000 probability located in
analysis: lysosome (membrane); 0.1021 probability located in microbody (peroxisome);
          0.1000 probability located in endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0363] 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
			Identities/
		NOV10a	Similarities
	Protein/Organism/	Residues/	for the
Geneseq	Length [Patent	Match	Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAM39588	Human polypeptide SEQ ID NO	65 . . . 136	51/78 (65%)	4e−20
	2733 - Homo sapiens, 111 aa.	28 . . . 105	56/78 (71%)
	[WO200153312-A1, 26 JUL. 2001]
AAM41374	Human polypeptide SEQ ID NO	65 . . . 135	52/77 (67%)	2e−19
	6305 - Homo sapiens, 106 aa.	29 . . . 105	57/77 (73%)
	[WO200153312-A1, 26 JUL. 2001]
ABG05297	Novel human diagnostic protein	65 . . . 136	48/78 (61%)	8e−19
	#5288 - Homo sapiens, 112 aa.	29 . . . 106	56/78 (71%)
	[WO200175067-A2, 11 OCT. 2001]
ABG05297	Novel human diagnostic protein	65 . . . 136	48/78 (61%)	8e−19
	#5288 - Homo sapiens, 112 aa.	29 . . . 106	56/78 (71%)
	[WO200175067-A2, 11 OCT. 2001]
ABG27048	Novel human diagnostic protein	64 . . . 135	45/78 (57%)	5e−15
	#27039 - Homo sapiens, 249 aa.	70 . . . 147	53/78 (67%)
	[WO200175067-A2, 11 OCT. 2001]

[0364] 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 for
Accession		Match	the Matched
Number	Protein/Organism/Length	Residues	Portion	Expect Value
Q8WTP9	XAGE-3 PROTEIN - Homo	65 . . . 136	51/78 (65%)	1e−19
	sapiens (Human), 111 aa.	28 . . . 105	56/78 (71%)
Q8WYS9	HYPOTHETICAL 12.3 KDA	65 . . . 136	51/78 (65%)	1e−19
	PROTEIN - Homo sapiens	28 . . . 105	56/78 (71%)
	(Human), 111 aa.
Q9HD64	G antigen family D 2 protein	1 . . . 136	59/149 (39%)	3e−18
	(XAGE-1) - Homo sapiens	1 . . . 140	76/149 (50%)
	(Human), 146 aa.
Q8WWM1	XAGE-5 PROTEIN - Homo	65 . . . 136	45/78 (57%)	9e−15
	sapiens (Human), 108 aa.	25 . . . 102	53/78 (67%)
Q96GT9	SIMILAR TO G ANTIGEN 8	65 . . . 136	39/78 (50%)	7e−13
	(XAGE-2 PROTEIN) - Homo	28 . . . 105	53/78 (67%)
	sapiens (Human), 111 aa.

Example 11

[0365] The NOV11 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11A.

TABLE 11BA
NOV11 Sequence Analysis
	SEQ ID NO:25	709 bp
NOV11a,	CGGCCGGTTTTGGTAGGCCCGGGCCGCCGCCAGGCCTCCGCCTGAGCCCGCACCCGCC
CG102532-01
DNA Sequence	ATGGACAACTACGCAGATCTTTCGGATACCGAGCTGACCACCTTGCTGCGCCGGTACA
	ACATCCCGCACGGGCCTGTAGTAGGATCAACTCGTAGGCTTTACGAGAAGAAGATCTT
	CGAGTACGAGACCCAGAGGCGGCGGCTCTCGCCCCCCAGCTCGTCCGCCGCCTCCTCT
	TATAGCTTCTCTGACTTGAATTCGACTAGAGGGGATGCAGATATGTATGATCTTCCCA
	AGAAAGAGGACGCTTTACTCTACCAGAGCAAGGGCTACAATGACGATCTTTTGTCTTC
	TTCTGAAGAGGAGTGCAAGGATAGGGAACGCCCCATGTACGGCCGGGACAGTGCCTAC
	CAGAGCATCACGCACTACCGCCCTGTTTCAGCCTCCAGGAGCTCCCTGGACCTGTCCT
	ATTATCCTACTTCCTCCTCCACCTCTTTTATGTCCTCCTCATCATCTTCCTCTTCATG
	GCTCACCCGCCGTGCCATCCGGCCTGAAAACCGTGCTCCTGGGGCTGGGCTGGGCCAG
	GATCGCCAGGTCCCGCTCTGGGGCCAGCTGCTGCTTTTCCTGGTCTTTGTGATCGTCC
	TCTTCTTCATTTACCACTTCATGCAGGCTGAAGAAGGCAACCCCTTCTGACTGCAGCC
	AAGCTAATTCCGG
	ORF Start: ATG at 59		ORF Stop: TGA at 686
	SEQ ID NO:26	209 aa	MW at 23844.1 kD
NOV11a,	MDNYADLSDTELTTLLRRYNIPHGPVVGSTRRLYEKKIFEYETQRRRLSPPSSSAASS
CG102532-01
Protein Sequence	YSFSDLNSTRGDADMYDLPKKEDALLYQSKGYNDDLLSSSEEECKDRERPMYGRDSAY
	QSITHYRPVSASRSSLDLSYYPTSSSTSFMSSSSSSSSWLTRPAIRPENPAPGAGLGQ
	DRQVPLWGQLLLFLVFVIVLFFIYHFMQAEEGNPF

[0366] Further analysis of the NOV11a protein yielded the following properties shown in Table 11B.

TABLE 11B
Protein Sequence Properties NOV11a
PSort     0.8500 probability located in endoplasmic reticulum (membrane); 0.6000 probability
analysis: located in nucleus; 0.4400 probability located in plasma
          membrane; 0.2323 probability located in microbody (peroxisome)
SignalP   No Known Signal Sequence Predicted
analysis:

[0367] A search of the NOV11a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 11C.

TABLE 11C
Geneseq Results for NOV11a
		NOV11a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY41294	Human emerin sequence	1 . . . 209	209/254 (82%)	e−112
	(EMD_HU) - Homo sapiens, 254	1 . . . 254	209/254 (82%)
	aa. [WO9954468-A1, 28 OCT.
	1999]
AAG02346	Human secreted protein, SEQ ID	1 . . . 51	51/51 (100%)	2e−23
	NO: 6427 - Homo sapiens, 51 aa.	1 . . . 51	51/51 (100%)
	[EP1033401-A2, 06 SEP. 2000]
AAY41297	Human thymopoietin gamma	6 . . . 209	60/231 (25%)	7e−10
	sequence - Homo sapiens, 345 aa.	114 . . . 333	107/231 (45%)
	[WO9954468-A1, 28 OCT. 1999]
AAR93188	Thymopoietin-gamma - Homo	6 . . . 209	60/231 (25%)	7e−10
	sapiens, 345 aa. [WO9609526-A1,	114 . . . 333	107/231 (45%)
	28 MAR. 1996]
AAR76499	Human thymopoietin-gamma -	6 . . . 209	60/231 (25%)	7e−10
	Homo sapiens, 345 aa.	114 . . . 333	107/231 (45%)
	[WO9517205-A1, 29 JUN. 1995]

[0368] In a BLAST search of public sequence databases, the NOV11a protein was found to have homology to the proteins shown in the BLASTP data in Table 11D.

TABLE 11D
Public BLASTP Results for NOV11a
		NOV11a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P50402	Emerin - Homo sapiens	1 . . . 209	209/254 (82%)	e−111
	(Human), 254 aa.	1 . . . 254	209/254 (82%)
Q63190	Emerin - Rattus norvegicus	1 . . . 209	162/256 (63%)	1e−81
	(Rat), 260 aa.	1 . . . 256	182/256 (70%)
O08579	Emerin - Mus musculus	1 . . . 209	162/255 (63%)	1e−81
	(Mouse), 259 aa.	1 . . . 255	182/255 (70%)
Q61032	THYMOPOIETIN GAMMA -	6 . . . 209	66/231 (28%)	2e−11
	Mus musculus (Mouse), 342 aa.	112 . . . 331	106/231 (45%)
AAC25390	THYMOPOIETIN GAMMA -	6 . . . 209	60/231 (25%)	2e−09
	Homo sapiens (Human), 345 aa.	114 . . . 333	107/231 (45%)

[0369] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11E.

TABLE 11E
Domain Analysis of NOV11a
		Identities/
Pfam		Similarities	Expect
Domain	NOV11a Match Region	for the Matched Region	Value
LEM	1 . . . 44	22/47 (47%)	4.4e−24
		43/47 (91%)

Example 12

[0370] The NOV12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12A.

TABLE 12A
NOV12 Sequence Analysis
                 SEQ ID NO:27         2812 bp
NOV12a,          CATTGAGTCGGCTTTTCTACTGCTTCGGCTAGGGTACCTTGTGACCATGTCTTCCAAG
CG102575-01      AAGAATAGAAAGCGGTTGAACCAAAGCGCGGAAAATGGTTCGTCCTTGCCCTCTGCTG
DNA Sequence     CTTCCTCTTGTGCGGAGGCACGGGCTCCTTCTGCTGGATCAGACTTCGCGGCAACCTC
                 CGGGACTCTGACGGTGACCAACTTATTAGAAAAGGGTAAAATTCCTAAAACATTCCAG
                 AATTCCCTTATTCATCTTGGACTCAACACTATGAAGTCTGCAAATATATGTATAGGTC
                 GACCAGTGTTGCTTACTAGTTTGAACGGAAAGCAAGAGGTATATACAGCCTGGCCTAT
                 GGCAGGATTTCCTGGAGGCAAGGTCGGCCTGAGTGAAATGGCACAGAAAAATGTGGGT
                 GTGAGGCCTGGTGATGCCATCCAGGTCCAGCCTCTTGTGGGTGCTGTGCTACAGGCTG
                 AGGAAATGGATGTGGCACTGAGTGACAAAGATATGGAAATTAATGAAGAAGAACTGAC
                 TGGTTGTATCCTGAGAAAACTAGATGGCAAGATTGTTTTACCAGGCAACTTTCTGTAT
                 TGTACATTCTATGGACGACCGTACAAGCTGCAAGTATTGCGAGTGAAAGGGGCAGATG
                 GCATGATATTGGGAGGGCCTCAGAGTGACTCTGACACTGATGCCCAAAGAATGGCCTT
                 TGAACAGTCCAGCATGGAAACCAGTAGCCTGGAGTTATCCTTACAGCTAAGCCAGTTA
                 GATCTGGAGGATACCCAGATCCCAACATCAAGAAGTACTCCTTATAAACCAATTGATG
                 ACAGAATTACAAATAAAGCCAGTGATGTTTTGCTGGATGTTACACAGAGCCCTGGAGA
                 TGGCAGTGGACTTATGCTAGAGGAAGTCACAGGTCTTAAATGTAATTTTGAATCTGCC
                 AGAGAAGGAAATGAGCAACTTACTGAAGAAGAGAGACTGCTAAAGTTCAGCATAGGAG
                 CAAAGTGCAATACTGATACTTTTTATTTTATTTCTTCAACAACAAGAGTCAATTTTAC
                 AGAGATTGATAAAAATTCAAAAGAGCAAGACAGTGATGTTAAAAGTAACTATGACCAT
                 GATAGAGGATTAAGTAGCCAGCTGAAAGCAATTAGAGAAATAATTGAATTGCCCCTCA
                 AAATTCCTGCCCCTAGAGGATTGTTACTTTATGGTCCTCCATGTACTGGAAAAACAAT
                 GATCGCCAGGGCTGTTGCTAATGAATTTGGAGCCTATGTTTCTGTAATTAATGGTCCT
                 GAAATTATAAGCAAGTTCTATGGTGAGACTGAAGCAAAGTTACGTCAGATATTTGCTG
                 AAGCCACTCTAAGACACCCATCAATTATTTTTATTGATGAGCTGGATGCACTTTGTCC
                 GAAAAGAGAGGGGGCCCAGAATGAAGTGGAAAAAAGAGTTGTGGCTTCACTCTTAACA
                 CTGATGGATGGCATTGGTTCAGAAGTAAGTGAAGGACAAGTGTTGGTTCTTGGGGCCA
                 CAAATCGCCCTCATGCCTTGGATGCTGCTCTCCGAAGACCTGGGCGATTTGATAAAGA
                 GATTGAGATTGGAGTTCCCAATGCTCAGGACCGGCTAGATATTCTCCAGAAACTGCTT
                 CGAAGGGTACCCCATTTGCTCACTGAGGCTGAGCTGCTGCAGCTGGCAAATAGTGCTC
                 ATGGATACGTTGGAGCAGACTTGAAAGTCTTGTGTAATGAAGCAGGTCTCTGTGCCTT
                 GCGGAGAATCCTGAAAAAACAGCCTAACCTCCCTGATGTCAAGGTGGCTGGACTGGTG
                 AAGATTACTCTGAAGGATTTCTTGCAGGCAATGAATGATATCAGACCCAGTGCCATGA
                 GGGAAATAGCAATTGATGTCCCAAATGTAAGTTATGATGATGTTGGTGGAGTTAGAAA
                 GCAAATGGCCCAAATCAGAGAGCTTGTTGAGCTTCCACTACGCCATCCTCAACTTTTC
                 AAATCTATTGGTATTCCTGCCCCTAGAGGATTGTTACTTTATGGTCCTCCATGTACTG
                 GAAAAACAATGATCGCCAGGGCTGTTGCTAATGAATTTGGAGCCTATGTTTCTGTAAT
                 TAATGGTCCTGAAATTATAAGCAAGTATGTTGGTGAGAGTGAACGTGCTGTGCGACAA
                 GTTTTTCAACGAGCCAAGAACTCAGCACCATCAATTATTTTTATTGATGAGCTGGATG
                 CACTTTGTCCGAAAAGAGAGGGGGCCCAGAATGAAGTGGAAAAAAGAGTTGTGGCTTC
                 ACTCTTAACACTGATGGATGGCATTGGTTCAGTAAGTATAGTGTTGGTTCTTGGGGCC
                 ACAAATCGCCCTCATGCCTTGGATGCTGCTCTCCGAAGACCTGGGCGATTTGATAAAG
                 AGATTGAGATTGGAGTTCCCAATGCTCAGGACCGGCTAGATATTCTCCAGAAACTGCT
                 TCGAAGGGTACCCCATTTGCTCACTGAGGCTGAGCTGCTGCAGCTGGCAAATAGTGCT
                 CATGGATACGTTGGAGCAGACTTGAAAGTCTTGTGTAATGAAGCAGGTGAGTGTGGTT
                 TGCTATGGGACATTCAAGCCAATCTCATCATGAAAAGACATTTCACTCAGGCCTTGAG
                 CACTGTGACACCTAGAATTCCTGAGTCATTGAGACGTTTTTATGAAGATTATCAAGAG
                 AAGAGTGGGCTGCATACACTCTGAGAAAATATATATATTCAAGATGCTGAAAATCCTT
                 TCCAGAGAAAATTGTTTCTTTTTAAAATTTTTGAGAGTGTTAAAAAAAATTTTACTAG
                 GCAAAATGTTTGAAGTATGTTCAGTAGA
                 ORF Start: ATG at 47 ORF Stop: TGA at 2690
                 SEQ ID NO:28         881 aa MW at 96419.5 kD
NOV12a,          MSSKKNRKRLNQSAENGSSLPSAASSCAEARAPSAGSDFAATSGTLTVTNLLEKGKIP
CG102575-01      KTFQNSLIHLGLNTMKSANICIGRPVLLTSLNGKQEVYTAWPMAGFPGGKVGLSEMAQ
Protein Sequence KNVGVRPGDAIQVQPLVGAVLQAEEMDVALSDKDMEINEEELTGCILRKLDGKIVLPG
                 NFLYCTFYGRPYKLQVLRVKGADGMILGGPQSDSDTDAQRMAFEQSSMETSSLELSLQ
                 LSQLDLEDTQIPTSRSTPYKPIDDRITNKASDVLLDVTQSPGDGSGLMLEEVTGLKCN
                 FESAREGNEQLTEEERLLKFSIGAKCNTDTFYFISSTTRVNFTEIDKNSKEQDSDVKS
                 NYDHDRGLSSQLKAIREIIELPLKIPAPRGLLLYGPPCTGKTMIARAVANEFGAYVSV
                 INGPEIISKFYGETEAKLRQIFAEATLRHPSIIFIDELDALCPKREGAQNEVEKRVVA
                 SLLTLMDGIGSEVSEGQVLVLGATNRPHALDAALRRPGRFDKEIEIGVPNAQDRLDIL
                 QKLLRRVPHLLTEAELLQLANSAHGYVGADLKVLCNEAGLCALRRILKKQPNLPDVKV
                 AGLVKITLKDFLQAMNDIRPSAMREIAIDVPNVSYDDVGGVRKQMAQIRELVELPLRH
                 PQLFKSIGIPAPRGLLLYGPPCTGKTMIARAVANEFGAYVSVINGPEIISKYVGESER
                 AVRQVFQRAKNSAPSIIFIDELDALCPKREGAQNEVEKRVVASLLTLMDGIGSVSIVL
                 VLGATNRPHALDAALRRPGRFDKEIEIGVPNAQDRLDILQKLLRRVPHLLTEAELLQL
                 ANSAHGYVGADLKVLCNEAGECGLLWDIQANLIMKRHFTQALSTVTPRIPESLRRFYE
                 DYQEKSGLHTL
                 SEQ ID NO:29         2789 bp
NOV12b,          CAGAGTTCGCCCTTCATTGAGTCGGCTTTTCTACTGCTTCGGCTAGGGTACCTTGTGA
CG102575-02      CCATGTCTTCCAAGAAGAATAGAAAGCGGTTGAACCAAAGCGCGGAAAATGGTTCGTC
DNA Sequence     CTTGCCCTCTGCTGCTTCCTCTTGTGTGGAGGCACGGGCTCCTTCTGCTGGATCAGAC
                 TTCGCGGCAACCTCCGGGACTCTGACGGTGACCAACTTATTAGAAAAGGTAGATGACA
                 AAATTCCTAAAACATTCCAGAATTCCCTTATTCATCTTGGACTCAACACTATGAAGTC
                 TGCAAATATATGTATAGGTCGACCAGTGTTGCTTACTAGTTTGAACGGAAAGCAAGAG
                 GTGTATACAGCCTGGCCTATGGCAGGATTTCCTGGAGGCAAGGTCGGCCTGAGTGAAA
                 TGGCACAGAAAAATGTGGGTGTGAGGCCTGGTGATGCCATCCAGGTCCAGCCTCTTGT
                 GGGTGCTGTGCTACAGGCTGAGGAAATGGATGTGGCACTGAGTGACAAAGATATGGAA
                 ATTAATGAAGAAGAACTGACTGGTTGTATCCTGAGAAAACTAGATGGCAAGATTGTTT
                 TACCAGGCAACTTTCTGTATTGTACATTCTATGGACGACCGTACAAGCTGCAAGTATT
                 GCGAGTGAAAGGGGCAGATGGCATGATATTGGGAGGGCCTCAGAGTGACTCTGACACT
                 GATGCCCAAAGAATGGCCTTTGAACAGTCCAGCATGGAAACCAGTAGCCTGGAGTTAT
                 CCTTACAGCTAAGCCAGTTAGATCTGGAGGATACCCAGATCCCAACATCAAGAAGTAC
                 TCCTTATAAACCAATTGATGACAGAATTACAAATAAAGCCAGTGATGTTTTGCTGGAT
                 GTTACACAGAGCCCTGGAGATGGCAGTGGACTTATGCTAGAGGAAGTCACAGGTCTTA
                 AATGTAATTTTGAATCTGCCAGAGAAGGAAATGAGCAACTTACTGAAGAAGAGAGACT
                 GCTAAAGTTCAGCATAGGAGCAAAGTGCAATACTGATACTTTTTATTTTATTTCTTCA
                 ACAACAAGAGTCAATTTTACAGAGATTGATAAAAATTCAAAAGAGCAAGACAACCAAT
                 TTAAAGTAACTTATGACATGATAGGAGGATTAAGTAGCCAGCTGAAAGCAATTAGAGA
                 AATAATTGAATTGCCCCTCAAACAGCCTGAGCTTTTCAAGAGTTATGGAATTCCTGCC
                 CCTAGAGGAGTGTTACTTTATGGTCCTCCAGGTACTGGAAAAACAATGATCGCCAGGG
                 CTGTTGCTAATGAAGTTGGAGCCTATGTTTCTGTAATTAATGGTCCTGAAATTATAAG
                 CAAATTCTATGGTGAGACTGAAGCAAAGTTACGTCAGATATTTGCTGAAGCCACTCTA
                 CGACACCCATCAATTATTTTTATTGATGAGCTGGATGCACTTTGTCCGAAAAGAGAGG
                 GGGCCCAGAATGAAGTGGAAAAAAGAGTTGTGGCTTCACTCTTAACACTGATGGATGG
                 CATTGGTTCAGAAGTAAGTGAAGGACAAGTGTTGGTTCTTGGGGCCACAAATCGCCCT
                 CATGCCTTGGATGCTGCTCTCCGAAGACCTGGGCGATTTGATAAAGAGATTGAGATTG
                 GAGTTCCCAATGCTCAGGACCGGCTAGATATTCTCCAGAAACTGCTTCGAAGGGTACC
                 CCATTTGCTCACTGAGGCTGAGCTGCTGCAGCTGGCAAATAGTGCTCATGGATACGTT
                 GGAGCAGACTTGAAAGTCTTGTGTAATGAAGCAGGTCTCTGTGCCTTGCGGAGAATCC
                 TGAAAAAACAGCCTAACCTCCCTGATGTCAAGGTGGCTGGACTGGTGAAGATTACTCT
                 GAAGGATTTCTTGCAGGCAATGAATGATATCAGACCCAGTGCCATGAGGGAAATAGCA
                 ATTGATGTCCCAAATGTATCCTGGTCAGATATAGGAGGACTGGAAAGTATCAAACTGA
                 AGTTGGAACAGGCTGTGGAATGGCCCTTAAAACATCCAGAGTCTTTCATTCGAATGGG
                 TATTCAGCCACCTAAAGGAGTTCTTCTCTATGGGCCACCTGGGTGCTCTAAAACAATG
                 ATAGCAAAGGCTTTGGCCAATGAGAGTGGACTGAATTTTCTAGCTATAAAGGGGCCTG
                 AATTAATGAATAAATATGTTGGTGAATCTGAAAGAGCAGTTAGAGAGACCTTCCGAAA
                 AGCAAGAGCAGTGGCGCCTTCCATTATTTTCTTTGATGAACTGGATGCCTTAGCAGTT
                 GAAAGGGGCAGTTCTTTAGGTGCTGGGAATGTAGCCGATCGTGTTTTGGCTCAGCTCT
                 TAACAGAAATGGATGGGATTGAACAGCTAAAGGATGTGACCATTTTGGCAGCTACTAA
                 CCGTCCAGATAGGATAGACAAGGCTTTGATGCGGCCTGGAAGAATTGATAGAATCATC
                 TATGTGCCTTTACCGGATGCAGCAACAAGAAGGGAAATATTTAAGCTGCAGTTTCACT
                 CCATGCCTGTCAGTAATGAAGTTGACCTGGATGAACTCATCCTTCAAACCGACGCATA
                 CTCAGGAGCAGAGATTGTAGCTGTCTGCAGAGAGGCAGCTCTTCTGGCTCTGGAAGAA
                 GACATTCAAGCCAATCTCATCATGAAAAGACATTTCACTCAGGCCTTGAGCACTGTGA
                 CACCTAGAATTCCTGAGTCATTGAGACGTTTTTATGAAGATTATCAAGAGAAGAGTGG
                 GCTGCATACACTCTGAGAAAATATATATATTCAAGATGCTGAAAATCCTTTCCAGAGA
                 AAATT
                 ORF Start: ATG at 61 ORF Stop: TGA at 2740
                 SEQ ID NO:30         893 aa MW at 97931.2 kD
NOV12b,          MSSKKNRKRLNQSAENGSSLPSAASSCVEARAPSAGSDFAATSGTLTVTNLLEKVDDK
CG102575-02      IPKTFQNSLIHLGLNTMKSANICIGRPVLLTSLNGKQEVYTAWPMAGFPGGKVGLSEM
Protein Sequence AQKNVGVRPGDAIQVQPLVGAVLQAEEMDVALSDKDMEINEEELTGCILRKLDGKIVL
                 PGNFLYCTFYGRPYKLQVLRVKGADGMILGGPQSDSDTDAQRMAFEQSSMETSSLELS
                 LQLSQLDLEDTQIPTSRSTPYKPIDDRITNKASDVLLDVTQSPGDGSGLMLEEVTGLK
                 CNFESAREGNEQLTEEERLLKFSIGAKCNTDTFYFISSTTRVNFTEIDKNSKEQDNQF
                 KVTYDMIGGLSSQLKAIREIIELPLKQPELFKSYGIPAPRGVLLYGPPGTGKTMIARA
                 VANEVGAYVSVINGPEIISKFYGETEAKLRQIFAEATLRHPSIIFIDELDALCPKREG
                 AQNEVEKRVVASLLTLMDGIGSEVSEGQVLVLGATNRPHALDAALRRPGRFDKEIEIG
                 VPNAQDRLDILQKLLRRVPHLLTEAELLQLANSAHGYVGADLKVLCNEAGLCALRRIL
                 KKQPNLPDVKVAGLVKITLKDFLQAMNDIRPSAMREIAIDVPNVSWSDIGGLESIKLK
                 LEQAVEWPLKHPESFIRMGIQPPKGVLLYGPPGCSKTMIAKALANESGLNFLAIKGPE
                 LMNKYVGESERAVRETFRKARAVAPSIIFFDELDALAVERGSSLGAGNVADRVLAQLL
                 TEMDGIEQLKDVTILAATNRPDRIDKALMRPGRIDRIIYVPLPDAATRREIFKLQFHS
                 MPVSNEVDLDELILQTDAYSGAEIVAVCREAALLALEEDIQANLIMKRHFTQALSTVT
                 PRIPESLRRFYEDYQEKSGLHTL

[0371] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 12B.

TABLE 12B
Comparison of NOV12a against NOV12b.
		Identities/
Protein	NOV12a Residues/	Similarities for
Sequence	Match Residues	the Matched Region
NOV12b	1 . . . 881	724/895 (80%)
	1 . . . 893	764/895 (84%)

[0372] Further analysis of the NOV12a protein yielded the following properties shown in Table 12C.

TABLE 12C
Protein Sequence Properties NOV12a
PSort     0.7000 probability located in plasma membrane; 0.3000 probability located in
analysis: microbody (peroxisome); 0.2000 probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in mitochondrial inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0373] A search of the NOV12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12D.

TABLE 12D
Geneseq Results for NOV12a
		NOV12a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU17209	Novel signal transduction pathway	261 . . . 823	442/575 (76%)	0.0
	protein, Seq ID 774 - Homo sapiens,	2 . . . 574	481/575 (82%)
	574 aa. [WO200154733-A1, 02
	AUG. 2001]
AAB59399	Protein tyrosine phosphatase related	337 . . . 848	229/527 (43%)	e−120
	sequence - Unidentified, 806 aa.	190 . . . 711	340/527 (64%)
	[WO200075339-A1, 14 DEC. 2000]
AAE09327	Human intracellular regulatory	337 . . . 848	229/527 (43%)	e−120
	molecule, VCP - Homo sapiens, 806	190 . . . 711	340/527 (64%)
	aa. [US6274312-B1, 14 AUG. 2001]
AAB05879	Human transitional endoplasmic	337 . . . 848	229/527 (43%)	e−120
	reticulum ATPase protein sequence -	190 . . . 711	340/527 (64%)
	Homo sapiens, 806 aa.
	[WO200034470-A1, 15 JUN. 2000]
ABB59038	Drosophila melanogaster	322 . . . 844	228/540 (42%)	e−117
	polypeptide SEQ ID NO 3906 -	170 . . . 704	342/540 (63%)
	Drosophila melanogaster, 801 aa.
	[WO200171042-A2, 27 SEPT. 2001]

[0374] In a BLAST search of public sequence databases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12E.

TABLE 12E
Public BLASTP Results for NOV12a
		NOV12a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
AAM00262	SPERMATOGENESIS	1 . . . 881	745/895 (83%)	0.0
	ASSOCIATED FACTOR - Homo	1 . . . 893	785/895 (87%)
	sapiens (Human), 893 aa.
Q9Z2K7	SPAF - Mus musculus (Mouse),	1 . . . 881	640/895 (71%)	0.0
	892 aa.	1 . . . 892	721/895 (80%)
Q9CXZ7	2510048F20RIK PROTEIN - Mus	1 . . . 881	640/896 (71%)	0.0
	musculus (Mouse), 893 aa.	1 . . . 893	721/896 (80%)
Q8ZYN4	AAA FAMILY ATPASE,	356 . . . 876	265/537 (49%)	e−136
	POSSIBLE CELL DIVISION	184 . . . 714	358/537 (66%)
	CONTROL PROTEIN CDC48 -
	Pyrobaculum aerophilum, 731 aa.
Q58556	Cell division cycle protein 48	309 . . . 855	271/578 (46%)	e−136
	homolog MJ1156 - Methanococcus	127 . . . 697	378/578 (64%)
	jannaschii, 903 aa.

[0375] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12F.

TABLE 12F
Domain Analysis of NOV12a
		Identities/
Pfam		Similarities	Expect
Domain	NOV12a Match Region	for the Matched Region	Value
AAA	378 . . . 566	95/217 (44%)	3.3e−75
		165/217 (76%)
AAA	652 . . . 837	98/217 (45%)	2e−77
		165/217 (76%)

Example 13

[0376] The NOV13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13A.

TABLE 13A
NOV13 Sequence Analysis
             SEQ ID NO:31         420 bp
NOV13a,      TGCAGAAGGTGACCCTGGGCCTGCTTGTGTTCCTGGCAGGCTTTCCTGTCCTGGACGC
CG102615-01  CAATGACCTAGAAGATAAAAACAGTCCTTTCTACTATGACTGGCACAGCCTCCAGGTT
DNA Sequence GGCGGGCTCATCTGCGCTGGGGTTCTGTGCGCCATGGGCATCATCATCGTCATGAGTG
             CAAAATGCAAATGCAAGTTTGGCCAGAAGTCCGGTCACCATCCAGGGGAGACTCCACC
             TCTCATCACCCCAGGCTCAGCCCAAAGCTGATGAGGACAGACCAGCTGAAATTGGGTG
             GAGGACCGTTCTCTGTCCCCAGGTCCTGTCTCTGCACAGAAACTTGAACTCCAGGATG
             GAATTCTTCCTCCTCTGCTGGGACTCCTTTGCATGGCAGGGCCTCATCTCACCTCTCG
             CAAGAGGGTCTCTT
             ORF Start: at 3      ORF Stop: TGA at 261
             SEQ ID NO:32         86 aa MW at 9131.6 kD
NOV13a,      QKVTLGLLVFLAGFPVLDANDLEDKNSPFYYDWHSLQVGGLICAGVLCAMGIIIVMSA
CG102615-01  KCKCKFGQKSGHHPGETPPLITPGSAQS
Protein Sequence
             SEQ ID NO:33         462 bp
NOV13b,      TCAGCCTGGTGAACCACACAGAGGCTGGGGCGAGGAGGATACCATCTGTCAGTCTTGG
CG102615-04  CTGGATGACATCATGGGAAGGGGGTATAGTGGGGCCTTGCAGGCCAGAGGTGGCTTGG
DNA Sequence AGGAGCCCCTGGAAAGAGGCTTAAGAGGCCAGCGCTCTGACATGCAGAAGGTGACCCT
             GGGCCTGCTTGTGTTCCTGGCAGGCTTTCCTGTCCTGGACGCCAATGACCTAGAAGAT
             AAAAACAGTCCTTTCTACTATGACTGGCACAGCCTCCAGGTTGGCGGGCTCATCTGCG
             CTGGGGTTCTGTGCGCCATGGGCATCATCATCGTCATGAGTGCAAAATGCAAATGCAA
             GTTTGGCCAGAAGTCCGGTCACCATCCAGGGGAGACTCCACCTCTCATCACCCCAGGC
             TCAGCCCAAAGCTGATGAGGACAGACCAGCTGAAATTGGGTGGAGGACCGTTCTCT
             ORF Start: ATG at 71 ORF Stop: TGA at 419
             SEQ ID NO:34         116 aa MW at 12362.2 kD
NOV13b,      MGRGYSGALQARGGLEEPLERGLRGQRSDMQKVTLGLLVFLAGFPVLDANDLEDKNSP
CG102615-04  FYYDWHSLQVGGLICAGVLCAMGIIIVMSAKCKCKFGQKSGHHPGETPPLITPGSAQS
Protein Sequence

[0377] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 13B.

TABLE 13B
Comparison of NOV13a against NOV13b.
	NOV13a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV13b	1 . . . 86	86/86 (100%)
	31 . . . 116	86/86 (100%)

[0378] Further analysis of the NOV13a protein yielded the following properties shown in Table 13C.

TABLE 13C
Protein Sequence Properties NOV13a
PSort     0.4600 probability located in plasma membrane;
analysis: 0.2000 probability located in
          lysosome (membrane); 0.1000 probability
          located in endoplasmic reticulum
          (membrane); 0.1000 probability located
          in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 20 and 21
analysis:

[0379] A search of the NOV13a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13D.

TABLE 13D
Geneseq Results for NOV13a
		NOV13a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAM23962	Human EST encoded protein SEQ	1 . . . 86	86/86 (100%)	7e−47
	ID NO: 1487 - Homo sapiens, 87 aa.	2 . . . 87	86/86 (100%)
	[WO200154477-A2, 02-AUG-2001]
AAW92959	Human MAT-8 protein - Homo	1 . . . 86	86/86 (100%)	7e−47
	sapiens, 87 aa. [WO9905276-A1,	2 . . . 87	86/86 (100%)
	04-FEB-1999]
AAY48304	Human prostate cancer-associated	1 . . . 86	86/86 (100%)	7e−47
	protein 1 - Homo sapiens, 87 aa.	2 . . . 87	86/86 (100%)
	[DE19811194-A1, 16-SEP-1999]
AAR90990	Human Mat-8 polypeptide - Homo	1 . . . 86	86/86 (100%)	7e−47
	sapiens, 87 aa. [WO9605322-A1,	2 . . . 87	86/86 (100%)
	22-FEB-1996]
AAB53415	Human colon cancer antigen protein	1 . . . 86	86/112 (76%)	2e−42
	sequence SEQ ID NO: 955 - Homo	39 . . . 150	86/112 (76%)
	sapiens, 150 aa. [WO200055351-A1,
	21-SEP-2000]

[0380] In a BLAST search of public sequence databases, the NOV13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13E.

TABLE 13E
Public BLASTP Results for NOV13a
			Identities/
		NOV13a	Similarities
Protein		Residues/	for the
Accession		Match	Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q14802	FXYD domain-containing ion transport	1 . . . 86	86/86 (100%)	2e−46
	regulator 3 precursor (Chloride	2 . . . 87	86/86 (100%)
	conductance inducer protein Mat-8)
	(Mammary tumor 8 kDa protein)
	(Phospholemman-like) - Homo sapiens
	(Human), 87 aa.
Q61835	FXYD domain-containing ion transport	1 . . . 86	63/86 (73%)	2e−33
	regulator 3 precursor (Chloride	2 . . . 87	72/86 (83%)
	conductance inducer protein Mat-8)
	(Mammary tumor 8 kDa protein)
	(Phospholemman-like) - Mus musculus
	(Mouse), 88 aa.
O97797	FXYD domain-containing ion transport	2 . . . 84	60/83 (72%)	8e−32
	regulator 3 precursor (Chloride	3 . . . 85	68/83 (81%)
	conductance inducer protein Mat-8)
	(Mammary tumor 8 kDa protein) - Sus
	scrofa (Pig), 88 aa.
Q9D2W0	FXYD domain-containing ion transport	1 . . . 86	45/86 (52%)	4e−21
	regulator 4 precursor (Channel	2 . . . 87	59/86 (68%)
	inducing factor) (CHIF) - Mus
	musculus (Mouse), 88 aa.
Q63113	FXYD domain-containing ion transport	3 . . . 86	44/84 (52%)	7e−20
	regulator 4 precursor (Channel	4 . . . 87	55/84 (65%)
	inducing factor) (CHIF)
	(Corticosteroid-induced protein) -
	Rattus norvegicus (Rat), 87 aa.

[0381] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13F.

TABLE 13F
Domain Analysis of NOV13a
		Identities/
		Similarities
	NOV13a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
ATP1G1_PLM_MAT8	19 . . . 74	27/57 (47%)	2.7e−35
		55/57 (96%)

Example 14

[0382] The NOV14 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 14A.

TABLE 14A
NOV14 Sequence Analysis
                 SEQ ID NO:35         1638 bp
NOV14a,          TTATCTAATATGTTTGTTTTAGCTACATCTTTATCAAGCCAAGTGAATCCTGACTGGC
CG102646-01      GAACATATATCATGCTTGCAGTATATTTTCTAATTTTACTTGTTATTGGATATTATGG
DNA Sequence     TTATAAGCAAGCAACCGGAGATTTAAGTGAATATATGCTTGGCGAAAGAAATATTGGT
                 CCATATGTCACTGCCTTATCTGCCGGAGCTTCAGATATGAGCGGTTGGATGATTATGG
                 GATTACCTGGAGAAGTTTATACTACAGGTTTATCAGCAGCATGGTTAGCTATTGGGTT
                 AACTATCGGAGCTTATGTTAACTACATACTTGTAGCACCAAGACTTCGTGTGTACACT
                 GAAAAAGCCAATGACTCAATTACATTGCCTAATTACTTTACACATCGTCTTAATGATA
                 ATTCCAATATTATTAAAATTATCTCTGGTGGTATCATTGTTGTATTTTTTACACTCTA
                 TACTCATTCAGGTATGGTATCAGGTGGTAAATTATTTGATAGTGCTTTTGGTTTAGAC
                 TATCATATTGGACTTATTTTAATCTCTGTCATTGTAATTTTATATACTTTTTTTGGTG
                 GCTATTTAGCAGTGTCGTTAACTGACTTTTTCCAAGGGGTTGTCATGTTAATTGCGAT
                 GGTTATGGTACCTATTGTAGCCATGATGCAGCTCGGAGGTATGGATGCTTTTTCACAA
                 GCAGCAACATTAAAACCTACTAATTTAGATTTATTTAAAGGAACAACTATTATAGGCA
                 TCATTTCATTCTTTGCTTGGGGATTAGGCTATTTTGGCCAGCCTCATATCATTGTACG
                 ATTTATGTCTATCAAATCCGTACGACAATTAAAAACGTCTAGAAGATTTGGTATTAGT
                 TGGATGGCTATTAGTTTAATCGGTGCAGTATGTGTTGGATTAATTGGCATTTCGTTTG
                 TACAAGATAAAGGTGTTGAATTAAAAGATCCAGAAACACTATTTATTTTAATGGGACA
                 AATTTTATTCCATCCTCTTGTAGGTGGGTTCCTACTTGCAGCCATTTTGGCAGCAATT
                 ATGAGTACGATTTCTTCCCAATTACTTGTGACTTCAAGTTCACTTACAGAAGATTTTT
                 ACAAGTTAATTCGTGGTGAAGAAGCAGCAAAGCAACATAAGAAAGAATTTTTATTAGT
                 GGGTCGATTATCTGTTGTAGTCGTTGCGATTATCTCCATCCTCATTGCATGGACGCCA
                 AATGACACTATCTTAAATCTTGTTGGTAACGCTTGGGCTGGATTCGGTGCAGCATTTG
                 GTCCACTGGTATTATTATCTCTCTATTCGAAAGGTTTAAGTCGTACTGGAGCTATTTC
                 TGGAATGTTATCAGGAGCAATTGTCGTCATTCTTTGGATTGTGTTTGTTAAACCATTA
                 GGAGCATATAATGATTTCTTTAATTTATATGAAATTATTCCTGGTTTCTTAACAAGTC
                 TTATTGTGACATATGTAGTGAGTCTTGTAACTAAAAAGCCAGATCTCAATGTTCAAAA
                 AGATTTAGAAGACGTCAAACGTATTGTAAAAGGACAATAAATTAATAATATTCAACGA
                 TGCTTAATGTCAATATTATTTCAATTAGTGCATTACTCTTATAATATGAAACACAAAT
                 AAATTTTTATACAT
                 ORF Start: ATG at 10 ORF Stop: TAA at 1546
                 SEQ ID NO:36         512 aa MW at 55813.4 kD
NOV14a,          MFVLATSLSSQVNPDWRTYIMLAVYFLILLVIGYYGYKQATGDLSEYMLGERNIGPYV
CG102646-01      TALSAGASDMSGWMIMGLPGEVYTTGLSAAWLAIGLTIGAYVNYILVAPRLRVYTEKA
Protein Sequence NDSITLPNYFTHRLNDNSNIIKIISGGIIVVFFTLYTHSGMVSGGKLFDSAFGLDYHI
                 GLILISVIVILYTFFGGYLAVSLTDFFQGVVMLIAMVMVPIVAMMQLGGMDAFSQAAT
                 LKPTNLDLFKGTTIIGIISFFAWGLGYFGQPHIIVRFMSIKSVRQLKTSRRFGISWMA
                 ISLIGAVCVGLIGISFVQDKGVELKDPETLFILMGQILFHPLVGGFLLAAILAAIMST
                 ISSQLLVTSSSLTEDFYKLIRGEEAAKQHKKEFLLVGRLSVVVVAIISILIAWTPNDT
                 ILNLVGNAWAGFGAAFGPLVLLSLYSKGLSRTGAISGMLSGAIVVILWIVFVKPLGAY
                 NDFFNLYEIIPGFLTSLIVTYVVSLVTKKPDLNVQKDLEDVKRIVKGQ

[0383] Further analysis of the NOV14a protein yielded the following properties shown in Table 14B.

TABLE 14B
Protein Sequence Properties NOV14a
PSort     0.8200 probability located in plasma membrane;
analysis: 0.4600 probability located in
          Golgi body; 0.3700 probability located in
          endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic
          reticulum (lumen)
SignalP   Cleavage site between residues 37 and 38
analysis:

[0384] A search of the NOV14a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14C.

TABLE 14C
Geneseq Results for NOV14a
		NOV14a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB76757	Corynebacterium glutamicum MCT	20 . . . 506	233/502 (46%)	e−127
	protein SEQ ID NO: 496 -	9 . . . 499	339/502 (67%)
	Corynebacterium glutamicum, 524
	aa. [WO200100805-A2, 04-JAN-2001]
AAG93195	C glutamicum protein fragment SEQ	20 . . . 506	233/502 (46%)	e−127
	ID NO: 6949 - Corynebacterium	9 . . . 499	339/502 (67%)
	glutamicum, 524 aa. [EP1108790-
	A2, 20-JUN-2001]
AAW20806	H. pylori transporter protein,	64 . . . 506	208/450 (46%)	e−112
	09ap20802orf27 - Helicobacter	5 . . . 445	306/450 (67%)
	pylori, 446 aa. [WO9640893-A1,
	19-DEC-1996]
AAG82596	S. epidermidis open reading frame	266 . . . 510	171/245 (69%)	1e−94
	protein sequence SEQ ID NO: 2286 -	163 . . . 407	208/245 (84%)
	Staphylococcus epidermidis, 408 aa.
	[WO200134809-A2, 17-MAY-2001]
AAB96626	Putative P. abyssi permease #22 -	24 . . . 508	174/503 (34%)	4e−83
	Pyrococcus abyssi, 537 aa.	11 . . . 507	275/503 (54%)
	[FR2792651-A1, 27-OCT-2000]

[0385] In a BLAST search of public sequence databases, the NOV14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14D.

TABLE 14D
Public BLASTP Results for NOV14a
		NOV14a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q99SY5	HIGH AFFINITY PROLINE	1 . . . 510	378/510 (74%)	0.0
	PERMEASE - Staphylococcus	1 . . . 510	443/510 (86%)
	aureus (strain Mu50/ATCC
	700699), and, 512 aa.
O30986	HIGH AFFINITY PROLINE	1 . . . 494	366/494 (74%)	0.0
	PERMEASE - Staphylococcus	1 . . . 493	431/494 (87%)
	aureus, 497 aa.
Q53584	PROLINE PERMEASE	1 . . . 494	366/494 (74%)	0.0
	HOMOLOG - Staphylococcus	1 . . . 493	430/494 (86%)
	aureus, 497 aa.
O06493	Osmoregulated proline transporter	20 . . . 494	268/478 (56%)	e−158
	(Sodium/proline symporter) -	7 . . . 473	371/478 (77%)
	Bacillus subtilis, 492 aa.
P94392	HOMOLOGUE OF PROLINE	54 . . . 504	243/452 (53%)	e−142
	PERMEASE OF E. COLI - Bacillus	1 . . . 442	336/452 (73%)
	subtilis, 449 aa.

[0386] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14E.

TABLE 14E
Domain Analysis of NOV14a
		Identities/
		Similarities
	NOV14a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
SSF	47 . . . 447	134/449 (30%)	5.7e−121
		318/449 (71%)

Example 15

[0387] The NOV15 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15A.

TABLE 15A
NOV15 Sequence Analysis
                 SEQ ID NO:37         1146 bp
NOV15a,          CTAGCTCGACAGCTTCCCGGCGGCTGCGCGATGGACAGCCCCGAGGTGACCTTCACTC
CG102878-01      TCGCCTATCTGGTGTTCGCCGTGTGCTTCGTGTTCACGCCCAACGAGTTCCACGCGGC
DNA Sequence     GGGGCTCACGGTGCAGAACCTGCTGTCGGGCTGGCTGGGCAGCGAGGACGCCGCCTTC
                 GTGCCCTTCCACTTGCGCCGCACGGCCGCCACGCTGTTGTGCCACTCGCTGCTGCCGC
                 TCGGCTACTATGTGGGCATGTGCCTTGCGGCTTCAGAAAAGCGGCTCCACGCCCTCAG
                 CCAGGCCCCTGAGGCCTGGCGGCTCTTCCTGCTGCTGGCCGTGACCCTCCCCTCCATC
                 GCCTGCATCCTGATCTACTACTGGTCCCGTGACCGGTGGGCCTGCCACCCACTGGCGC
                 GCACCCTGGCCCTCTACGCCCTCCCACAGTCTGGCTGGCAGGCTGTTGCCTCCTCTGT
                 CAACACTGAGTTCCGGCGGATTGACAAGTTTGCCACCGGTGCACCAGGTGCCCGTGTG
                 ATTGTGACAGACACGTGGGTGATGAAGGTAACCACCTACCGAGTGCACGTGGCCCAGC
                 AGCAGGACGTGCACCTGACTGTGACGGAGTCTCGGCAGCATGAGCTCTCGCCAGACTC
                 GAACTTGCCCGTGCAGCTCCTCACCATCCGTGTGGCCAGCACCAACCCTGCTGTGCAG
                 GCCTTTGACATCAGGCTGAACTCCACTGAGTACGGGGAGCTCTGCGAGAAGCTCCGGG
                 CACCCATCCGCAGGGCAGCCCATGTGGTCATCCACCAGAGCCTGGGCGACCTGTTCCT
                 GGAGACATTTGCCTCCCTGGTAGAGGTCAACCCGGCCTACTCAGTGCCCAGCAGCCAG
                 GAGCTGGAGGCCTGCATAGGCTGCATGCAGACACGTGCCAGCGTGAAGCTGGTGAAGA
                 CCTGCCAGGAGGCAGCCACAGGCGAGTGCCAGCAGTGTTACTGCCGCCCCATGTGGTG
                 CCTCACCTGCATGGGCAAGTGGTTCGCCAGCCGCCAGGACCCCCTGCGCCCTGACACC
                 TGGCTGGCCAGCCGCGTGCCCTGCCCCACCTGCCGCGCACGCTTCTGCATCCTGGATG
                 TGTGCACCGTGCGCTGAGTGGGCTGGGGCCTTGAGGTGACTCTG
                 ORF Start: ATG at 31 ORF Stop: TGA at 1117
                 SEQ ID NO:38         362 aa MW at 40433.3 kD
NOV15a,          MDSPEVTFTLAYLVFAVCFVFTPNEFHAAGLTVQNLLSGWLGSEDAAFVPFHLRRTAA
CG102878-01      TLLCHSLLPLGYYVGMCLAASEKRLHALSQAPEAWRLFLLLAVTLPSIACILIYYWSR
Protein Sequence DRWACHPLARTLALYALPQSGWQAVASSVNTEFRRIDKFATGAPGARVIVTDTWVMKV
                 TTYRVHVAQQQDVHLTVTESRQHELSPDSNLPVQLLTIRVASTNPAVQAFDIRLNSTE
                 YGELCEKLRAPIRRAAHVVIHQSLGDLFLETFASLVEVNPAYSVPSSQELEACIGCMQ
                 TRASVKLVKTCQEAATGECQQCYCRPMWCLTCMGKWFASRQDPLRPDTWLASRVPCPT
                 CRARFCILDVCTVR
                 SEQ ID NO:39         1115 bp
NOV15b,          TTCGCCCTTGGCTGCGCGATGGACAGCCCCGAGGTGACCTTCACTCTCGCCTATCTGG
CG102878-02      TGTTCGCCGTGTGCTTCGTGTTCACGCCCAACGAGTTCCACGCGGCGGGGCTCACGGT
DNA Sequence     GCAGAACCTGCTGTCGGGCTGGCTGGGCAGCGAGGACGCCGCCTTCGTGCCCTTCCAC
                 TTGCGCCGCACGGCCGCCACGCTGTTGTGCCACTCGCTGCTGCCGCTCGGCTACTACG
                 TGGGCATGTGCCTTGCGGCTTCAGAAAAGCGGCTCCACGCCCTCAGCCAGGCCCCTGA
                 GGCCTGGCGGCTCTTCCTGCTGCTGGCCGTGACCCTCCCCTCCATTGCCTGCATCCTG
                 ATCTACTACTGGTCCCGTGACCGGTGGGCCTGCCACCCACTGGCGCGCACCCTGGCCC
                 TCTACGCCCTCCCACAGTCTGGCTGGCAGGCTGTTGCCTCCTCTGTCAACACTGAGTT
                 CCGGCGGATTGACAAGTTTGCCACCGGTGCACCAGGTGCCCGTGTGATTGTGACAGAC
                 ACGTGGGTGATGAAGGTAACCACCTACCGAGTGCACGTGGCCCAGCAGCAGGACGTGC
                 ACCTGACTGTGACGGAGTCTCGGCAGCATGAGCTCTCGCCAGACTCGAACTTGCCCGT
                 GCAGCTCCTCACCATCCGTGTGGCCAGCACCAACCCTGCTGTGCAGGCCTTTGACATC
                 TGGCTGAACTCCACTGAGTACGGGGAGCTCTGCGAGAAGCTCCGGGCACCCATCCGCA
                 GGGCAGCCCATGTGGTCATCCACCAGAGCCTGGGCGACCTGTTCCTGGAGACATTTGC
                 CTCCCTGGTAGAGGTCAACCCGGCCTACTCAGTGCCCAGCAGCCAGGAGCTGGAGGCC
                 TGCATAGGCTGCATGCAGACACGTGCCAGCGTGAAGCTGGTGAAGACCTGCCAGGAGG
                 CAGCCACAGGCGAGTGCCAGCAGTGTTACTGCCGCCCCATGTGGTGCCTCACCTGCAT
                 GGGCAAGTGGTTCGCCAGCCGCCAGGACCCCCTGCGCCCTGACACCTGGCTGGCCAGC
                 CGCGTGCCCTGCCCCACCTGCCGCGCACGCTTCTGCATCCTGGATGTGTGCACCGTGC
                 GCTGATGTGGCGG
                 ORF Start: ATG at 19 ORF Stop: TGA at 1105
                 SEQ ID NO: 40        362 aa MW at 40463.4 kD
NOV15b,          MDSPEVTFTLAYLVFAVCFVFTPNEFHAAGLTVQNLLSGWLGSEDAAFVPFHLRRTAA
CG102878-02      TLLCHSLLPLGYYVGMCLAASEKRLHALSQAPEAWRLFLLLAVTLPSIACILIYYWSR
Protein Sequence DRWACHPLARTLALYALPQSGWQAVASSVNTEFRRIDKFATGAPGARVIVTDTWVMKV
                 TTYRVHVAQQQDVHLTVTESRQHELSPDSNLPVQLLTIRVASTNPAVQAFDIWLNSTE
                 YGELCEKLRAPIRRAAHVVIHQSLGDLFLETFASLVEVNPAYSVPSSQELEACIGCMQ
                 TRASVKLVKTCQEAATGECQQCYCRPMWCLTCMGKWFASRQDPLRPDTWLASRVPCPT
                 CRARFCILDVCTVR

[0388] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 15B.

TABLE 15B
Comparison of NOV15a against NOV15b.
	NOV15a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV15b	1 . . . 362	361/362 (99%)
	1 . . . 362	361/362 (99%)

[0389] Further analysis of the NOV15a protein yielded the following properties shown in Table 15C.

TABLE 15C
Protein Sequence Properties NOV15a
PSort     0.6760 probability located in plasma membrane;
analysis: 0.1000 probability located in
          endoplasmic reticulum (membrane);
          0.1000 probability located in
          endoplasmic reticulum (lumen);
          0.1000 probability located in outside
SignalP   Cleavage site between residues 29 and 30
analysis:

[0390] A search of the NOV15a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15D.

TABLE 15D
Geneseq Results for NOV15a
		NOV15a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAG81377	Human AFP protein sequence SEQ	1 . . . 362	360/362 (99%)	0.0
	ID NO: 272 - Homo sapiens, 362 aa.	1 . . . 362	360/362 (99%)
	[WO200129221-A2, 26-APR-2001]
ABB69639	Drosophila melanogaster	1 . . . 358	122/389 (31%)	7e−60
	polypeptide SEQ ID NO: 35709 -	1 . . . 383	200/389 (51%)
	Drosophila melanogaster, 409 aa.
	[WO200171042-A2, 27-SEP-2001]
AAG23427	Arabidopsis thaliana protein	337 . . . 362	13/26 (50%)	2.8
	fragment SEQ ID NO: 26729 -	77 . . . 102	16/26 (61%)
	Arabidopsis thaliana, 284 aa.
	[EP1033405-A2, 06-SEP-2000]
AAG23426	Arabidopsis thaliana protein	337 . . . 362	13/26 (50%)	2.8
	fragment SEQ ID NO: 26728 -	206 . . . 231	16/26 (61%)
	Arabidopsis thaliana, 413 aa.
	[EP1033405-A2, 06-SEP-2000]
ABG11786	Novel human diagnostic protein	285 . . . 354	23/89 (25%)	3.6
	#11777 - Homo sapiens, 198 aa.	54 . . . 141	37/89 (40%)
	[WO200175067-A2, 11-OCT-2001]

[0391] In a BLAST search of public sequence databases, the NOV15a protein was found to have homology to the proteins shown in the BLASTP data in Table 15E.

TABLE 15E
Public BLASTP Results for NOV15a
		NOV15a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
CAC38627	SEQUENCE 271 FROM	1 . . . 362	361/362 (99%)	0.0
	PATENT WO0129221 - Homo	1 . . . 362	361/362 (99%)
	sapiens (Human), 362 aa.
Q9DCF3	0610039G24RIK PROTEIN -	1 . . . 362	323/362 (89%)	0.0
	Mus musculus (Mouse), 362 aa.	1 . . . 362	341/362 (93%)
Q96GP5	SIMILAR TO RIKEN CDNA	1 . . . 226	226/226 (100%)	e−129
	0610039G24 GENE - Homo	1 . . . 226	226/226 (100%)
	sapiens (Human), 232 aa.
Q9VN16	CG14646 PROTEIN - Drosophila	1 . . . 358	122/389 (31%)	2e−59
	melanogaster (Fruit fly), 409 aa.	1 . . . 383	200/389 (51%)
Q95TM4	LD39811P - Drosophila	20 . . . 358	116/370 (31%)	1e−55
	melanogaster (Fruit fly), 393 aa.	4 . . . 367	190/370 (51%)

Example 16

[0392] The NOV16 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16A.

TABLE 16A
NOV16 Sequence Analysis
                 SEQ ID NO:41         2765 bp
NOV 16a,         CTGGCGGCGTCGCATGGAGGGCTCTGGGGGCGGTGCGGGCGAGCGGGCGCCGCTGCTG
CG103459-01      GGCGCGCGGCGGGCGGCGGCGGCCGCGGCGGCGGCTGGGGCGTTCGCGGGCCGGCGCG
DNA Sequence     CGGCGTGCGGGGCCGTGCTGCTGACGGAGCTGCTGGAGCGCGCCGCTTTCTACGGCAT
                 CACGTCCAACCTGGTGCTATTCCTGAACGGGGCGCCGTTCTGCTGGGAGGGCGCGCAG
                 GCCAGCGAGGCGCTGCTGCTCTTCATGGGCCTCACCTACCTGGGCTCGCCGTTCGGAG
                 GCTGGCTGGCCGACGCGCGGCTGGGCCGGGCGCGCGCCATCCTGCTGAGCCTGGCGCT
                 CTACCTGCTGGGCATGCTGGCCTTCCCGCTGCTGGCCGCGCCCGCCACGCGAGCCGCG
                 CTCTGCGGTTCCGCGCGCCTGCTCAACTGCACGGCGCCTGGTCCCGACGCCGCCGCCC
                 GCTGCTGCTCACCGGCCACCTTCGCGGGGCTGGTGCTGGTGGGCCTGGGCGTGGCCAC
                 CGTCAAGGCCAACATCACGCCCTTCGGCGCCGACCAGGTTAAAGATCGAGGTCCGGAA
                 GCCACTAGGAGATTTTTTAATTGGTTTTATTGGAGCATTAACCTGGGAGCGATCCTGT
                 CGTTAGGTGGCATTGCCTATATTCAGCAGAACGTCAGCTTTGTCACTGGTTATGCGAT
                 CCCCACTGTCTGCGTCGGCCTTGCTTTTGTGGCCTTCCTCTGTGGCCAGAGCGTTTTC
                 ATCACCAAGCCTCCTGATGGCAGTGCCTTCACCGATATGTTCAAGATACTGACGTATT
                 CCTGCTGTTCCCAGAAGCGAAGTGGAGAGCGCCAGAGTAATGGTGAAGGCATTGGAGT
                 CTTTCAGCAATCTTCTAAACAAAGTCTGTTTGATTCATGTAAGATGTCTCATGGTGGG
                 CCATTTACAGAAGAGAAAGTGGAAGATGTGAAAGCTCTGGTCAAGATTGTCCCTGTTT
                 TCTTGGCTTTGATACCTTACTGGACAGTGTATTTCCAAATGCAGACAACATATGTTTT
                 ACAGAGTCTTCATTTGAGGATTCCAGAAATTTCAAATATTACAACCACTCCTCACACG
                 CTCCCTGCAGCCTGGCTGACCATGTTTGATGCTGTGCTCATCCTCCTGCTCATCCCTC
                 TGAAGGACAAACTGGTCGATCCCATTTTGAGAAGACATGGCCTGCTCCCATCCTCCCT
                 GAAGAGGATCGCCGTGGGCATGTTCTTTGTCATGTGCTCAGCCTTTGCTGCAGGAATT
                 TTGGAGAGTAAAAGGCTGAACCTTGTTAAAGAGAAAACCATTAATCAGACCATCGGCA
                 ACGTCGTCTACCATGCTGCCGATCTGTCGCTGTGGTGGCAGGTGCCGCAGTACTTGCT
                 GATTGGGATCAGCGAGATCTTTGCAAGTATCGCAGGCCTGGAATTTGCATACTCAGCT
                 GCCCCCAAGTCCATGCAGAGTGCCATAATGGGCTTGTTCTTTTTCTTCTCTGGCGTCG
                 GGTCGTTCGTGGGTTCTGGACTGCTGGCACTGGTGTCTATCAAAGCCATCGGATGGAT
                 GAGCAGTCACACAGACTTTGGTAATATTAACGGCTGCTATTTGAACTATTACTTTTTT
                 CTTCTGGCTGCTATTCAAGGAGCTACCCTCCTGCTTTTCCTCATTATTTCTGTGAAAT
                 ATGACCATCATCGAGACCATCAGCGATCAAGAGCCAATGGCGTGCCCACCAGCAGGAG
                 GGCCTGACCTTCCTGAGGCCATGTGCGGTTTCTGAGGCTGACATGTCAGTAACTGACT
                 GGGGTGCACTGAGAACAGGCAAGACTTTAAATTCCCATAAAATGTCTGACTTCACTGA
                 AACTTGCATGTTGCCTGGATTGATTTCTTCTTTCCCTCTATCCAAAGGAGCTTGGTAA
                 GTGCCTTACTGCAGCGTGTCTCCTGGCACGCTGGGCCCTCCGGGAGGAGAGCTGCAGA
                 TTTCGAGTATGTCGCTTGTCATTCAAGGTCTCTGTGAATCCTCTAGCTGGGTTCCCTT
                 TTTTACAGAAACTCACAAATGGAGATTGCAAAGTCTTGGGGAACTCCACGTGTTAGTT
                 GGCATCCCAGTTTCTTAAACAAATAGTATCACCTGCTTCCCATAGCCATATCTCACTG
                 TAAAAAAAAAAATTAATAAACTGTTACTTATATTTAAGAAAGTGAGGATTTTTTTTTT
                 TTAAAGATAAAAGCATGGTCAGATGCTGCAAGGATTTTACATAAATGCCATATTTATG
                 GTTTCCTTCCTGAGAACAATCTTGCTCTTGCCATGTTCTTTGATTTAGGCTGGTAGTA
                 AACACATTTCATCTGCTGCTTCAAAAAGTACTTACTTTTTAAACCATCAACATTACTT
                 TTCTTTCTTAAGGCAAGGCATGCATAAGAGTCATTTGAGACCATGTGTCCCATCTCAA
                 GCCACAGAGCAACTCACGGGGTACTTCACACCTTACCTAGTCAGAGTGCTTATATATA
                 GCTTTATTTTGGTACGATTGAGACTAAAGACTGATCATGGTTGTATGTAAGGAAAACA
                 TTCTTTTGAACAGAAATAGTGTAATTAAAAATAATTGAAAGTGTTAAATGTGAACTTG
                 AGCTGTTTGACCAGTCACATTTTTGTATTGTTACTGTACGTGTATCTGGGGCTTCTCC
                 GTTTGTTAATACTTTTTCTGTATTTGTTGCTGTATTTTTGGCATAACTTTATTATAAA
                 AAGCATCTCAAATGCGAAAAAAAAAAAAAAAAAAAAAAA
                 ORF Start: ATG at 14 ORF Stop: TGA at 1745
                 SEQ ID NO:42         577 aa MW at 62004.6 kD
NOV16a,          MEGSGGGAGERAPLLGARRAAAAAAAAGAFAGRRAACGAVLLTELLERAAFYGITSNL
CG103459-01      VLFLNGAPFCWEGAQASEALLLFMGLTYLGSPFGGWLADARLGRARAILLSLALYLLG
Protein Sequence MLAFPLLAAPATRAALCGSARLLNCTAPGPDAAARCCSPATFAGLVLVGLGVATVKAN
                 ITPFGADQVKDRGPEATRRFFNWFYWSINLGAILSLGGIAYIQQNVSFVTGYAIPTVC
                 VGLAFVAFLCGQSVFITKPPDGSAFTDMFKILTYSCCSQKRSGERQSNGEGIGVFQQS
                 SKQSLFDSCKMSHGGPFTEEKVEDVKALVKIVPVFLALIPYWTVYFQMQTTYVLQSLH
                 LRIPEISNITTTPHTLPAAWLTMFDAVLILLLIPLKDKLVDPILRRHGLLPSSLKRIA
                 VGMFFVMCSAFAAGILESKRLNLVKEKTINQTIGNVVYHAADLSLWWQVPQYLLIGIS
                 EIFASIAGLEFAYSAAPKSMQSAIMGLFFFFSGVGSFVGSGLLALVSIKAIGWMSSHT
                 DFGNINGCYLNYYFFLLAAIQGATLLLFLIISVKYDHHRDHQRSRANGVPTSRRA

[0393] Further analysis of the NOV16a protein yielded the following properties shown in Table 16B.

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

[0394] A search of the NOV16a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16C.

TABLE 16C
Geneseq Results for NOV16a
		NOV16a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAU12071	Human PHT1 variant protein from	1 . . . 577	577/577 (100%)	0.0
	Caco-2 cells - Homo sapiens, 577	1 . . . 577	577/577 (100%)
	aa. [WO200192468-A2, 06-DEC-2001]
AAU12068	Human PHT1 protein isolated from	1 . . . 577	577/577 (100%)	0.0
	Caco-2 cells - Homo sapiens, 577	1 . . . 577	577/577 (100%)
	aa. [WO200192468-A2, 06-DEC-2001]
AAU12070	Human PHT1 variant protein from	1 . . . 577	575/577 (99%)	0.0
	BeWo cells - Homo sapiens, 577	1 . . . 577	576/577 (99%)
	aa. [WO200192468-A2, 06-DEC-2001]
AAE16771	Human transporter and ion channel-8	1 . . . 577	576/577 (99%)	0.0
	(TRICH-8) protein - Homo	1 . . . 576	576/577 (99%)
	sapiens, 576 aa. [WO200192304-
	A2, 06-DEC-2001]
AAB82821	Human proton/oligonucleotide	22 . . . 577	555/556 (99%)	0.0
	transporter hPHT1 polypeptide -	1 . . . 556	555/556 (99%)
	Homo sapiens, 556 aa.
	[WO200160854-A1, 23-AUG-2001]

[0395] In a BLAST search of public sequence databases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16D.

TABLE 16D
Public BLASTP Results for NOV16a
		NOV16a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O09014	PEPTIDE/HISTIDINE	9 . . . 576	500/578 (86%)	0.0
	TRANSPORTER - Rattus	3 . . . 571	531/578 (91%)
	norvegicus (Rat), 572 aa.
Q91W98	SIMILAR TO PEPTIDE	9 . . . 576	496/578 (85%)	0.0
	TRANSPORTER 3 - Mus	3 . . . 573	531/578 (91%)
	musculus (Mouse), 574 aa.
AAH28394	SIMILAR TO PEPTIDE	117 . . . 577	460/461 (99%)	0.0
	TRANSPORTER 3 - Homo	1 . . . 461	460/461 (99%)
	sapiens (Human), 461 aa.
Q9P2X9	PEPTIDE TRANSPORTER 3 -	9 . . . 558	289/570 (50%)	e−152
	Homo sapiens (Human), 581 aa.	14 . . . 564	379/570 (65%)
Q9WU80	CAMP INDUCIBLE 1	8 . . . 567	279/577 (48%)	e−144
	PROTEIN - Mus musculus	6 . . . 570	366/577 (63%)
	(Mouse), 578 aa.

[0396] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16E.

TABLE 16E
Domain Analysis of NOV16a
		Identities/
		Similarities
	NOV16a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
PTR2	103 . . . 496	109/448 (24%)	6.7e−103
		310/448 (69%)

Example 17

[0397] The NOV17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A.

TABLE 17A
NOV17 Sequence Analysis
                 SEQ ID NO:43        1393 bp
NOV17a,          CCCATGGAGGCTCCGGGACCCCGCGCCTTGCGGACTGCGCTCTGTGGCGGCTGTTGCT
CG104210-01      GCCTCCTCCTATGTGCCCAGCTGGCTGTGGCTGGTAAAGGAGCTCGAGGCTTTGGGAG
DNA Sequence     GGGAGCCCTGATCCGCCTGAATATCTGGCCGGCGGTCCAAGGGGCCTGCAAACAGCTG
                 GAGGTCTGTGAGCACTGCGTGGAGGGAGACAGAGCGCGCAATCTCTCCAGCTGCATGT
                 GGGAGCAGTGCCGGCCAGAGGAGCCAGGTCACTGTGTGGCCCAATCTGAGGTGGTCAA
                 GGAAGGTTGCTCCATCTACAACCGCTCAGAGGCATGTCCAGCTGCTCACCACCACCCC
                 ACCTATGAACCGAAGACAGTCACAACAGGTAGCCCCCCAGTCCCTGAGGCCCACAGCC
                 CTGGATTTGACGGGGCCAGCTTTATCGGAGGTGTCGTGCTGGTGTTGAGCCTACAGGC
                 GGTGGCTTTCTTTGTGCTGCACTTCCTCAAGGCCAAGGACAGCACCTACCAGACGCTG
                 TGAGTACCTGGCCAGCAGCAAGTACCTGAGTCCCAGCTCACCTCCTGGTTCCTGCCCC
                 ACCGTTCCCCTTCAGTACCCAGGGTGCTGTCTTCTCCACTGGCAAGCCCTCAGGACGG
                 TGACAGCGTGCTCCATGTGAGCCACACCCCTTTTGTCTCCTCCAGTTGGGGTGTTTCC
                 TTTGTCAGATGTTGGCTGGGACCAGGACTCAGCCTGGGCCAGTCTAGGAGCCCAGCTG
                 AGCCCTCCTGTGTCTTTTCCCTTCATGCTGCCAGCAGGGAAGAGAACCAGTAGGTGCC
                 AGCCCAGCAACCTGTGGCCCGCGTTTCTGTGGCTGTGGGCAGGAGCTGGGCCTTGTGT
                 CTAGTTGGGTTTTGCTCTGAGAAGGGGAGCTGTGCTGAGGCCCTCTGTGTGCCGTGTG
                 TGCTGTGGGGCGGGTCGCCACAGCCTGTGTTAAAGTGTTTGCTCTTCCTCTGCTGCCT
                 CCTCTCGAGGCAGGGGGTCCTTGGCTGGCTGAGGCAGTGTCACCTTCCTGAGTGTCCT
                 CTTTGGCCTCTGCAGAATCTGACCCCTTTGGGCCTGGACTCCATCCTGAGGGGAAAGG
                 AGGATGCAGAGGGTGGCCTCTGGGCACCCTTGTGGGTAAGCGGGGGGCGGGGGCGGGA
                 AAAACTCTGGCCGCCAGTTTTTGGCTCCTGCGGGCACCAAGCAGGCTCAGTGTCTGAT
                 GCTTGACATCTCCTCCTGTCCTGGGCCTGGAACCTGCAGCTGAGAAAATCCCTCAACC
                 ACCTCGTCTCCTCCATCGCCCCTGCTGGGCCCCCCAGCCTGACAGTGGGTTGTATGCC
                 TGCCTCTTTCCACCAACTGGCCTGGGCACTGCCCCCAAATAAAGGAACTCTGCACTGC
                 A
                 ORF Start: ATG at 4 ORF Stop: TGA at 523
                 SEQ ID NO:44        173 aa MW at 18421.0 kD
NOV17a,          MEAPGPRALRTALCGGCCCLLLCAQLAVAGKGARGFGRGALIRLNIWPAVQGACKQLE
CG104210-01      VCEHCVEGDRARNLSSCMWEQCRPEEPGHCVAQSEVVKEGCSIYNRSEACPAAHHHPT
Protein Sequence YEPKTVTTGSPPVPEAHSPGFDGASFIGGVVLVLSLQAVAFFVLHFLKAKDSTYQTL
                 SEQ ID NO:45        561 bp
NOV17b,          CCCATGGAGGCTCCGGGACCCCGCGCCTTGCGGACTGCGCTCTGTGGCGGCTGTTGCT
CG104210-02      GCCTCCTCCTATGTGCCCAGCTGGCTGTGGCTGGTAAAGGAGCTCGAGGCTTTGGGAG
DNA Sequence     GGGAGCCCTGATCCGCCTGAATATCTGGCCGGCGGTCCAAGGGGCCTGCAAACAGCTG
                 GAGGTCTGTGAGCACTGCGTGGAGGGAGACAGAGCGCGCAATCTCTCCAGCTGCGTGT
                 GGGAGCAGTGCCGGCCAGAGGAGCCAGGACACTGTGTGGCCCAATCTGAGGTGGTCAA
                 GGAAGGTTGCTCCATCTACAACCGCTCAGAGGCATGTCCAGCTGCTCACCACCACCCC
                 ACCTATGAACCGAAGACAGTCACAACAGGGAGCCCCCCAGTCCCTGAGGCCCACAGCC
                 CTGGATTTGACGGGGCCAGCTTTATCGGAGGTGTCGTGCTGGTGTTGAGCCTACAGGC
                 GGTGGCTTTCTTTGTGCTGCACTTCCTCAAGGCCAAGGACAGCACCTACCAGACGCTG
                 TGAGTACCTGGCCAGCAGCAAGTACCTGAGTCCCAGCTC
                 ORF Start: ATG at 4 ORF Stop: TGA at 523
                 SEQ ID NO:46        173 aa MW at 18389.0 kD
NOV17b,          MEAPGPRALRTALCGGCCCLLLCAQLAVAGKGARGFGRGALIRLNIWPAVQGACKQLE
CG104210-02      VCEHCVEGDRARNLSSCVWEQCRPEEPGHCVAQSEVVKEGCSIYNRSEACPAAHHHPT
Protein Sequence YEPKTVTTGSPPVPEAHSPGFDGASFIGGVVLVLSLQAVAFFVLHFLKAKDSTYQTL
                 SEQ ID NO:47        349 bp
NOV17c,          CACCGGATCCGGTAAAGGAGCTCGAGGCTTTGGGAGGGGAGCCCTGATCCGCCTGAAT
272249075 DNA    ATCTGGCCGGCGGTCCAAGGGGCCTGCAAACAGCTGGAGGTCTGTGAGCACTGCGTGG
Sequence         AGGGAGACAGAGCGCGCAATCTCTCCAGCTGCATGTGGGAGCAGTGCCGGCCAGAGGA
                 GCCAGGACACTGTGTGGCCCAATCTGAGGTGGTCAAGGAAGGTTGCTCCATCTACAAC
                 CGCTCAGAGGCATGTCCAGCTGCTCACCACCACCCCACCTATGAACCGAAGACAGTCA
                 CAACAGGGAGCCCCCCAGTCCCTGAGGCCCACAGCCCTGGATTTGACGGGGTCGACGG
                 C
                 ORF Start: at 2     ORF Stop: end of sequence
                 SEQ ID NO:48        116 aa MW at 12383.7 kD
NOV17c,          TGSGKGARGFGRGALIRLNIWPAVQGACKQLEVCEHCVEGDRARNLSSCMWEQCRPEE
272249075        PGHCVAQSEVVKEGCSIYNRSEACPAAHHHPTYEPKTVTTGSPPVPEAHSPGFDGVDG
Protein Sequence

[0398] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 17B.

TABLE 17B
Comparison of NOV17a against NOV17b and NOV17c.
	NOV17a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV17b	1 . . . 173	139/173 (80%)
	1 . . . 173	140/173 (80%)
NOV17c	41 . . . 139	99/99 (100%)
	15 . . . 113	99/99 (100%)

[0399] Further analysis of the NOV17a protein yielded the following properties shown in Table 17C.

TABLE 17C
Protein Sequence Properties NOV17a
PSort     0.6850 probability located in endoplasmic
analysis: reticulum (membrane); 0.6400
          probability located in plasma membrane;
          0.4600 probability located in Golgi
          body; 0.1000 probability located in
          endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 30 and 31
analysis:

[0400] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17D.

TABLE 17D
Geneseq Results for NOV17a
		NOV17a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAE03827	Human gene 10 encoded secreted	1 . . . 173	173/173 (100%)	e−103
	protein HBINS58, SEQ ID NO: 73 -	1 . . . 173	173/173 (100%)
	Homo sapiens, 173 aa.
	[WO200136440-A1, 25-MAY-2001]
AAE03852	Human gene 10 encoded secreted	1 . . . 160	159/160 (99%)	5e−94
	protein HBINS58, SEQ ID NO: 98 -	1 . . . 160	159/160 (99%)
	Homo sapiens, 210 aa.
	[WO200136440-A1, 25-MAY-2001]
AAB58415	Lung cancer associated polypeptide	73 . . . 173	41/124 (33%)	8e−10
	sequence SEQ ID 753 - Homo	95 . . . 214	56/124 (45%)
	sapiens, 214 aa. [WO200055180-
	A2, 21-SEP-2000]
AAG03771	Human secreted protein, SEQ ID	73 . . . 173	38/124 (30%)	1e−07
	NO: 7852 - Homo sapiens, 197 aa.	78 . . . 197	52/124 (41%)
	[EP1033401-A2, 06-SEP-2000]
ABB65987	Drosophila melanogaster	116 . . . 173	29/60 (48%)	9e−05
	polypeptide SEQ ID NO: 24753 -	127 . . . 183	35/60 (58%)
	Drosophila melanogaster, 183 aa.
	[WO200171042-A2, 27-SEP-2001]

[0401] In a BLAST search of public sequence databases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17E.

TABLE 17E
Public BLASTP Results for NOV17a
		NOV17a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9D6W7	2310047N01RIK PROTEIN -	1 . . . 173	140/173 (80%)	1e−82
	Mus musculus (Mouse), 172 aa.	1 . . . 171	150/173 (85%)
Q9BPV0	CD164 ISOFORM DELTA 4 -	73 . . . 173	41/111 (36%)	6e−11
	Homo sapiens (Human), 184 aa.	78 . . . 184	56/111 (49%)
Q9CVT7	CD164 ANTIGEN - Mus	25 . . . 173	51/173 (29%)	2e−10
	musculus (Mouse), 161 aa	5 . . . 161	67/173 (38%)
	(fragment).
Q9QX82	ENDOLYN PRECURSOR -	54 . . . 173	41/140 (29%)	4e−10
	Rattus norvegicus (Rat), 195 aa.	57 . . . 195	59/140 (41%)
Q9Z317	MGC-24V - Mus musculus	54 . . . 173	44/144 (30%)	7e−10
	(Mouse), 197 aa.	58 . . . 197	58/144 (39%)

Example 18

[0402] The NOV18 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 18A.

TABLE 18A
NOV18 Sequence Analysis
                 SEQ ID NO:49         788 bp
NOV18a,          CTTTTGCCTTTATGCAACCAACATGGAGATTTTGTACCATGTCCTGTTCTTAGTGCTT
CG104251-01      GAATGTCCTAACCTGAAGCTGAAGAAGCCGCCCTGGCTGCACATGCTGTCGGCCATGA
DNA Sequence     CTGTATGCTCTGGTGGTGGTGTCTTCCTCATTACCGGAGGAATCATTTATGATGTTAT
                 TGTTGAACCTCCAAGTGTTGGCTCTATGACTGATGAACATGGGCATCAGAGGCCAGTA
                 GCTTTCTTTGCCTATAGAGTAAATGGACAATATATTATGGAAGGACTTGCATCCAGCT
                 TCCTGTTTACAATGGGAGGTTTAGGTTTCATAATCCTGGACCAATTGAATGCACCAAA
                 TATCCCAAAACTCAATAGATTTCTTCTTCTATTCATTGGATTTGTCTGTGTTCTATTG
                 AGTATTTTCATGGCTAGAGTATTCATGAGAATGAAACTGCCGAGCTATCTGATGGGTT
                 AGAGTGCCTTTGAGAAGAAATCAGTGGATACTGGATTTTTTCTTGTCAATGAAGTTTT
                 AAAGGCTGTACCAATCCTCTAATATGAAATGTGGAAAAGAATGAAGAGCAGCAGTAAA
                 AGAAATATCTAGTGAAAAAACAGGAAGCGTATTGAAGCTTGGACTAGAATTTCTTCTT
                 GGTATTAAAGAGACAAGTTTATCACAGAATTTTTTTTCCTGCTGGCCTATTGCTATAC
                 CAATGATGTTGAGTGGCATTTTCTTTTTAGTTTTTCATTAAAATATATTCCATATCTA
                 CAACTATAATATCAAATAAAGTGATTATTTTTTA
                 ORF Start: ATG at 23 ORF Stop: TAG at 464
                 SEQ ID NO:50         147 aa MW at 16447.7 kD
NOV18a,          MEILYHVLFLVLECPNLKLKKPPWLHMLSAMTVCSGGGVFLITGGIIYDVIVEPPSVG
CG104251-01      SMTDEHGHQRPVAFFAYRVNGQYIMEGLASSFLFTMGGLGFIILDQLNAPNIPKLNRF
Protein Sequence LLLFIGFVCVLLSIFMARVFMRMKLPSYLMG

[0403] Further analysis of the NOV18a protein yielded the following properties shown in Table 18B.

TABLE 18B
Protein Sequence Properties NOV18a
PSort     0.6400 probability located in plasma membrane;
analysis: 0.4600 probability located in
          Golgi body; 0.3700 probability located in
          endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic
          reticulum (lumen)
SignalP   Cleavage site between residues 42 and 43
analysis:

[0404] A search of the NOV18a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 18C.

TABLE 18C
Geneseq Results for NOV18a
		NOV18a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAY53631	A bone marrow secreted protein	1 . . . 147	133/149 (89%)	1e−69
	designated BMS155 - Homo	1 . . . 149	135/149 (90%)
	sapiens, 149 aa. [WO9933979-A2,
	08-JUL-1999]
AAY53042	Human secreted protein clone	1 . . . 147	133/149 (89%)	1e−69
	pu282_10 protein sequence SEQ ID	1 . . . 149	135/149 (90%)
	NO: 90 - Homo sapiens, 149 aa.
	[WO9957132-A1, 11-NOV-1999]
AAB12143	Hydrophobic domain protein	1 . . . 147	133/149 (89%)	1e−69
	isolated from WERI-RB cells -	1 . . . 149	135/149 (90%)
	Homo sapiens, 149 aa.
	[WO200029448-A2, 25-MAY-2000]
AAY59670	Secreted protein 108-005-5-0-F6-FL -	1 . . . 147	133/149 (89%)	1e−69
	Homo sapiens, 149 aa.	1 . . . 149	135/149 (90%)
	[WO9940189-A2, 12-AUG-1999]
AAY60146	Human endometrium tumor EST	1 . . . 147	133/149 (89%)	1e−69
	encoded protein 206 - Homo	23 . . . 171	135/149 (90%)
	sapiens, 171 aa. [DE19817948-A1,
	21-OCT-1999]

[0405] In a BLAST search of public sequence databases, the NOV18a protein was found to have homology to the proteins shown in the BLASTP data in Table 18D.

TABLE 18D
Public BLASTP Results for NOV18a
		NOV18a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9NRP0	DC2 (HYDROPHOBIC PROTEIN	1 . . . 147	133/149 (89%)	3e−69
	HSF-28) (HYPOTHETICAL 16.8	1 . . . 149	135/149 (90%)
	KDA PROTEIN) - Homo sapiens
	(Human), 149 aa.
Q9P075	HSPC307 - Homo sapiens	1 . . . 147	133/149 (89%)	3e−69
	(Human), 167 aa (fragment).	19 . . . 167	135/149 (90%)
Q9CPZ2	2310008M10RIK PROTEIN	1 . . . 147	132/149 (88%)	6e−69
	(RIKEN CDNA 2310008M10	1 . . . 149	135/149 (90%)
	GENE) - Mus musculus (Mouse),
	149 aa.
Q9P1R4	HDCMD45P - Homo sapiens	1 . . . 147	132/149 (88%)	2e−68
	(Human), 160 aa (fragment).	12 . . . 160	134/149 (89%)
AAH24224	SIMILAR TO DC2 PROTEIN -	40 . . . 147	96/108 (88%)	7e−50
	Homo sapiens (Human), 119 aa.	12 . . . 119	100/108 (91%)

Example 19

[0406] The NOV19 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 19A.

TABLE 19A
NOV19 Sequence Analysis
                 SEQ ID NO:51         3761 bp
NOV19a,          GGGCGCGCCGAGCCGGGCGCGGGGGCGCTGAACGGCGGAGCGGGAGCGGCCGGAGGAG
CG104934-01      CCATGGACTGCAGCCTCGTGCGGACGCTCGTGCACAGATACTGTGCAGGAGAAGAGAA
DNA Sequence     TTGGGTGGACAGCAGGACCATCTACGTGGGACACAGGGAGCCACCTCCGGGCGCAGAG
                 GCCTACATCCCACAGAGATACCCAGACAACAGGATCGTCTCGTCCAAGTACACATTTT
                 GGAACTTTATACCCAAGAATTTATTTGAACAATTCAGAAGAGTAGCCAACTTTTATTT
                 CCTTATCATATTTCTGGTGCAGTTGATTATTGATACACCCACAAGTCCAGTGACAAGC
                 GGACTTCCACTCTTCTTTGTCATTACTGTGACGGCTATCAAACAGGGTTATGAAGACT
                 GGCTTCGACATAAAGCAGACAATGCCATGAACCAGTGTCCTGTTCATTTCATTCAGCA
                 CGGCAAGCTCGTTCGGAAACAAAGTCGAAAGCTGCGAGTTGGGGACATTGTCATGGTT
                 AAGGAGGACGAGACCTTTCCCTGCGACTTGATCTTCCTTTCCAGCAACCGGGGAGATG
                 GGACGTGCCACGTCACCACCGCCAGCTTGGATGGAGAATCCAGCCATAAAACGCATTA
                 CGCGGTCCAGGACACCAAAGGCTTCCACACAGAGGAGGATATCGGCGGACTTCACGCC
                 ACCATCGAGTGTGAGCAGCCCCAGCCCGACCTCTACAAGTTCGTGGGTCGCATCAACG
                 TTTACAGTGACCTGAATGACCCCGTGGTGAGGCCCTTAGGATCGGAAAACCTGCTGCT
                 TAGAGGAGCTACACTGAAGAACACTGAGAAAATCTTTGGTGTGGCTATTTACACGGGA
                 ATGGAAACCAAGATGGCATTAAATTATCAATCAAAATCTCAGAAGCGATCTGCCGTGG
                 AAAAATCGATGAATGCGTTCCTCATTGTGTATCTCTGCATTCTGATCAGCAAAGCCCT
                 GATAAACACTGTGCTGAAATACATGTGGCAGAGTGAGCCCTTTCGGGATGAGCCGTGG
                 TATAATCAGAAAACGGAGTCGGAAAGGCAGAGGAATCTGTTCCTCAAGGCATTCACGG
                 ACTTCCTGGCCTTCATGGTCCTCTTTAACTACATCATCCCTGTGTCCATGTACGTCAC
                 GGTCGAGATGCAGAAGTTCCTCGGCTCTTACTTCATCACCTGGGACGAAGACATGTTT
                 GACGAGGAGACTGGCGAGGGGCCTCTGGTGAACACGTCGGACCTCAATGAAGAGCTGG
                 GACAGGTGGAGTACATCTTCACAGACAAGACCGGCACCCTCACGGAAAACAACATGGA
                 GTTCAAGGAGTGCTGCATCGAAGGCCATGTCTACGTGCCCCACGTCATCTGCAACGGG
                 CAGGTCCTCCCAGAGTCGTCAGGAATCGACATGATTGACTCGTCCCCCAGCGTCAACG
                 GGAGGGAGCGCGAGGAGCTGTTTTTCCGGGCCCTCTGTCTCTGCCACACCGTCCAGGT
                 GAAAGACGATGACAGCGTAGACGGCCCCAGGAAATCGCCGGACGGGGGGAAATCCTGT
                 GTGTACATCTCATCCTCGCCCGACGAGGTGGCGCTGGTCGAAGGTGTCCAGAGACTTG
                 GCTTTACCTACCTAAGGCTGAAGGACAATTACATGGAGATATTAAACAGGGAGAACCA
                 CATCGAAAGGTTTGAATTGCTGGAAATTTTGAGTTTTGACTCAGTCAGAAGGAGAATG
                 AGTGTAATTGTAAAATCTGCTACAGGAGAAATTTATCTGTTTTGCAAAGGAGCAGATT
                 CTTCGATATTCCCCCGAGTGATAGAAGGCAAAGTTGACCAGATCCGAGCCAGAGTGGA
                 GCGTAACGCAGTGGAGGGGCTCCGAACTTTGTGTGTTGCTTATAAAAGGCTGATCCAA
                 GAAGAATATGAAGGCATTTGTAAGCTGCTGCAGGCTGCCAAAGTGGCCCTTCAAGATC
                 GAGAGAAAAAGTTAGCAGAAGCCTATGAGCAAATAGAGAAAGATCTTACTCTGCTTGG
                 TGCTACAGCTGTTGAGGACCGGCTGCAGGAGAAAGCTGCAGACACCATCGAGGCCCTG
                 CAGAAGGCCGGGATCAAAGTCTGGGTTCTCACGGGAGACAAGATGGAGACGGCCGCGG
                 CCACGTGCTACGCCTGCAAGCTCTTCCGCAGGAACACGCAGCTGCTGGAGCTGACCAC
                 CAAGAGGATCGAGGAGCAGAGCCTGCACGACGTCCTGTTCGAGCTGAGCAAGACGGTC
                 CTGCGCCACAGCGGGAGCCTGACCAGAGACAACCTGTCCGGACTTTCAGCAGATATGC
                 AGGACTACGGTTTAATTATCGACGGAGCTGCACTGTCTCTGATAATGAAGCCTCGAGA
                 AGACGGGAGTTCCGGCAACTACAGGGAGCTCTTCCTGGAAATCTGCCGGAGCTGCAGC
                 GCGGTGCTCTGCTGCCGCATGGCGCCCTTGCAGAAGGCTCAGATTGTTAAATTAATCA
                 AATTTTCAAAAGAGCACCCAATCACGTTAGCAATTGGCGATGGTGCAAATGATGTCAG
                 CATGATTCTGGAAGCGCACGTGGGCATAGGTGTCATCGGCAAGGAAGGCCGCCAGGCT
                 GCCAGGAACAGCGACTATGCAATCCCAAAGTTTAAGCATTTGAAGAAGATGCTGCTTG
                 TTCACGGGCATTTTTATTACATTAGGATCTCTGAGCTCGTGCAGTACTTCTTCTATAA
                 GAACGTCTGCTTCATCTTCCCTCAGTTTTTATACCAGTTCTTCTGTGGGTTTTCACAA
                 CAGACTTTGTACGACACCGCGTATCTGACCCTCTACAACATCAGCTTCACCTCCCTCC
                 CCATCCTCCTGTACAGCCTCATGGAGCAGCATGTTGGCATTGACGTGCTCAAGAGAGA
                 CCCGACCCTGTACAGGGACGTCGCCAAGAATGCCCTGCTGCGCTGGCGCGTGTTCATC
                 TACTGGACGCTCCTGGGACTGTTTGACGCACTGGTGTTCTTCTTTGGTGCTTATTTCG
                 TGTTTGAAAATACAACTGTGACAAGCAACGGGCAGATATTTGGAAACTGGACGTTTGG
                 AACGCTGGTATTCACCGTGATGGTGTTCACAGTTACACTAAAGCTTGCATTGGACACA
                 CACTACTGGACTTGGATCAACCATTTTGTCATCTGGGGGTCGCTGCTGTTCTACGTTG
                 TCTTTTCGCTTCTCTGGGGAGGAGTGATCTGGCCGTTCCTCAACTACCAGAGGATGTA
                 CTACGTGTTCATCCAGATGCTGTCCAGCGGGCCCGCCTGGCTGGCCATCGTGCTGCTG
                 GTGACCATCAGCCTCCTTCCCGACGTCCTCAAGAAAGTCCTGTGCCGGCAGCTGTGGC
                 CAACAGCAACAGAGAGAGTCCAGAATGGGTGCGCACAGCCTCGGGACCGCGACTCAGA
                 ATTCACCCCTCTTGCCTCTCTGCAGAGCCCAGGCTACCAGAGCACCTGTCCCTCGGCC
                 GCCTGGTACAGCTCCCACTCTCAGCAGGTGACACTCGCGGCCTGGAAGGAGAAGGTGT
                 CCACGGAGCCCCCACCCATCCTCGGCGGTTCCCATCACCACTGCAGTTCCATCCCAAG
                 TCACAGCTGCCCTAGGTCCCGTGTGGGAATGCTCGTGTGATGGATGGTCCTAAGCCTG
                 TGGAGACTGTGCACGTGCCTCTTCCTGGCCCCCAGCAGGCAAGGAGGGGGGTCACAGG
                 CCTTGCCCTCGAGCATGGCACCCTGGCCGCCTGGACCCAGCACTGTGGT
                 ORF Start: ATG at 61 ORF Stop: TGA at 3634
                 SEQ ID NO:52         1191 aa MW at 135846.0 kD
NOV19a,          MDCSLVRTLVHRYCAGEENWVDSRTIYVGHREPPPGAEAYIPQRYPDNRIVSSKYTFW
CG104934-01      NFIPKNLFEQFRRVANFYFLIIFLVQLIIDTPTSPVTSGLPLFFVITVTAIKQGYEDW
Protein Sequence LRHKADNAMNQCPVHFIQHGKLVRKQSRKLRVGDIVMVKEDETFPCDLIFLSSNRGDG
                 TCHVTTASLDGESSHKTHYAVQDTKGFHTEEDIGGLHATIECEQPQPDLYKFVGRINV
                 YSDLNDPVVRPLGSENLLLRGATLKNTEKIFGVAIYTGMETKMALNYQSKSQKRSAVE
                 KSMNAFLIVYLCILISKALINTVLKYMWQSEPFRDEPWYNQKTESERQRNLFLKAFTD
                 FLAFMVLFNYIIPVSMYVTVEMQKFLGSYFITWDEDMFDEETGEGPLVNTSDLNEELG
                 QVEYIFTDKTGTLTENNMEFKECCIEGHVYVPHVICNGQVLPESSGIDMIDSSPSVNG
                 REREELFFRALCLCHTVQVKDDDSVDGPRKSPDGGKSCVYISSSPDEVALVEGVQRLG
                 FTYLRLKDNYMEILNRENHIERFELLEILSFDSVRRRMSVIVKSATGEIYLFCKGADS
                 SIFPRVIEGKVDQIRARVERNAVEGLRTLCVAYKRLIQEEYEGICKLLQAAKVALQDR
                 EKKLAEAYEQIEKDLTLLGATAVEDRLQEKAADTIEALQKAGIKVWVLTGDKMEDAAA
                 TCYACKLFRRNTQLLELTTKRIEEQSLHDVLFELSKTVLRHSGSLTRDNLSGLSADMQ
                 DYGLIIDGAALSLIMKPREDGSSGNYRELFLEICRSCSAVLCCRMAPLQKAQIVKLIK
                 FSKEHPITLAIGDGANDVSMILEAHVGIGVIGKEGRQAARNSDYAIPKFKHLKKMLLV
                 HGHFYYIRISELVQYFFYKNVCFIFPQFLYQFFCGFSQQTLYDTAYLTLYNISFTSLP
                 ILLYSLMEQHVGIDVLKRDPTLYRDVAKNALLRWRVFIYWTLLGLFDALVFFFGAYFV
                 FENTTVTSNGQIFGNWTFGTLVFTVMVFTVTLKLALDTHYWTWINHFVIWGSLLFYVV
                 FSLLWGGVIWPFLNYQRMYYVFIQMLSSGPAWLAIVLLVTISLLPDVLKKVLCRQLWP
                 TATERVQNGCAQPRDRDSEFTPLASLQSPGYQSTCPSAAWYSSHSQQVTLAAWKEKVS
                 TEPPPILGGSHHHCSSIPSHSCPRSRVGMLV

[0407] Further analysis of the NOV19a protein yielded the following properties shown in Table 19B.

TABLE 19B
Protein Sequence Properties NOV19a
PSort     0.6000 probability located in plasma membrane;
analysis: 0.4000 probability located in
          Golgi body; 0.3000 probability located
          in endoplasmic reticulum (membrane);
          0.0300 probability located in mitochondrial
          inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0408] A search of the NOV19a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 19C.

TABLE 19C
Geneseq Results for NOV19a
		NOV19a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAO14200	Human transporter and ion	1 . . . 1191	1190/1192 (99%)	0.0
	channel TRICH-17 - Homo	1 . . . 1192	1191/1192 (99%)
	sapiens, 1192 aa. [WO200204520-
	A2, 17-JAN-2002]
AAB42368	Human ORFX ORF2132	338 . . . 1109	770/772 (99%)	0.0
	polypeptide sequence SEQ ID	1 . . . 772	772/772 (99%)
	NO: 4264 - Homo sapiens, 797 aa.
	[WO200058473-A2, 05-OCT-2000]
AAG67546	Amino acid sequence of a human	22 . . . 1109	657/1119 (58%)	0.0
	transporter protein - Homo	18 . . . 1106	833/1119 (73%)
	sapiens, 1177 aa. [WO200164878-
	A2, 07-SEP-2001]
AAO14203	Human transporter and ion	22 . . . 1109	583/1119 (52%)	0.0
	channel TRICH-20 - Homo	18 . . . 1040	755/1119 (67%)
	sapiens, 1096 aa. [WO200204520-
	A2, 17-JAN-2002]
AAM39290	Human polypeptide SEQ ID NO:	370 . . . 1109	424/771 (54%)	0.0
	2435 - Homo sapiens, 815 aa.	1 . . . 744	544/771 (69%)
	[WO200153312-A1, 26-JUL-2001]

[0409] In a BLAST search of public sequence databases, the NOV19a protein was found to have homology to the proteins shown in the BLASTP data in Table 19D.

TABLE 19D
Public BLASTP Results for NOV19a
		NOV19a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P98197	Potential phospholipid-	1 . . . 1189	1074/1195 (89%)	0.0
	transporting ATPase IH (EC	1 . . . 1185	1117/1195 (92%)
	3.6.3.1) - Mus musculus (Mouse),
	1187 aa.
P98196	Potential phospholipid-	338 . . . 1109	772/772 (100%)	0.0
	transporting ATPase IS (EC	1 . . . 772	772/772 (100%)
	3.6.3.1) - Homo sapiens (Human),
	797 aa (fragment).
Q8WX24	BB206I21.1 (ATPASE, CLASS	14 . . . 997	633/992 (63%)	0.0
	VI, TYPE 11C) - Homo sapiens	1 . . . 962	770/992 (76%)
	(Human), 962 aa (fragment).
Q9N0Z4	RING-FINGER BINDING	22 . . . 1109	574/1123 (51%)	0.0
	PROTEIN - Oryctolagus	10 . . . 1036	752/1123 (66%)
	cuniculus (Rabbit), 1107 aa
	(fragment).
Q9Y2G3	Potential phospholipid-	486 . . . 1109	358/625 (57%)	0.0
	transporting ATPase IR (EC	1 . . . 601	462/625 (73%)
	3.6.3.1) - Homo sapiens (Human),
	672 aa (fragment).

[0410] PFam analysis predicts that the NOV19a protein contain the domains shown in the Table 19E.

TABLE 19E
Domain Analysis of NOV19a
		Identities/
		Similarities
	NOV19a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
Hydrolase	408 . . . 846	46/448 (10%)	0.0058
		258/448 (58%)

Example 20

[0411] The NOV20 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 20A.

TABLE 20A
NOV20 Sequence Analysis
                 SEQ ID NO:53         2588 bp
NOV20a,          AGTTCCGAACAGAAGGCTGTGTATTCTCTGCCGCTTATTGTGGCCTCGACAGGCCATG
CG105463-01      GTTACTTTGGCCACTGCCAGAGCAGCCTTGGCACTATGGAGGAGCCTAGGGCTACCCC
DNA Sequence     TCAGCTGTACTTGGGGCTGGTCCTGCAGTTGCTACCCAGGGTTATGGCAGCACTGCCT
                 GAAGGTGTGAGACCAAATTCGAATCCTTATGGTTTTCCATGGGAATTGGTGATATGTG
                 CAGCTGTCCTTGGATTTGTTGCTGTTCCCTTTTTTTTGTGGAGAAGTTTTAGATCGGT
                 TAGGAGTCGGCTTTATGTGGGAAGAGAGAAAGAGCTTGCTATAGCGCTTTCTGGACTA
                 ATTGAAGAAAAATGTAGACTACTTGAAAAATTTAGCCTTGTTCAAAAAGAGTATGAAG
                 GCTATGAAGTAGAGTCATCTTTAGAGGATGCCAGCTTTGAGAAGGAGGCAACAGAAGC
                 ACAAAGTCTGGAGGCAAACTGTGAAAAGCTGAACAGGTCCAATTCTGAACTGGAGCAT
                 GAAATACTCTGTCTAGAAAAGGGGATAAAAGAAGAGAAATCTAAACATTCTGAACAAG
                 ATGAGGTGATGGCAGATATTTCCAAAAAGATACAGTCTCTAGAAGATGAGTCAAAATC
                 CCTCAAATCACTACTAACTGAAGCCAAAATGACCTTCAAGGGATTTCAAATGAATGAA
                 GAAAAACTGGAGATAGGAATACAAGATGCTTCGAGTGAAAATTGTCAACTTCAGGAAA
                 GCCAGAAACAGCTTTTGCAAGAAGCTGAAGTATGGAAAGAACAAGTGAGTGAACTTAA
                 TAAACAGAAAATAACATTTGAAGACTCCAAAGTACACGCAGAACAAGTTCTAAATGAT
                 AAAGAAAATCACATCGAGACTCTGACTGAACGCTTGCTAAAGATCAAAGATCAGGCTG
                 CTGTGCTGGAAGAAGACATAACGGATGATGGTAACTTGGAATTAGAAATGAACAGTGA
                 ATTGAAAGATGGTGCTTACTTAGATAATCCTCCAAAAGGAGCTTTGAAGAAACTGATT
                 CATGCTGCTAAGTTAAATGCTTCTTTAACAACCTTAGAAGGAGAAAGAAACCAATTTA
                 TATTCAGTTATCTGAAGTTGATAAAACCAAGGAAGAGCTTAGAGAGCATATTAAAAAT
                 CTTCAGACGGAACAAGCATCTTTGCAGTCGGAAAACACACATTTTGAAAGTGAGAATC
                 AGAAACTTCAACAGAAAGTTAATGACTGAGTTATATCAAGAAAATGAAATGAAACTCT
                 ACAGGAAATTAATAGTAGAGGAAAATAACCGGTTAGAGAAAGAGAAACTTTCTAAAGT
                 AGACGAAATGATCAGCCATGCCACTGAAGAGCTGGAGACCTGCAGAAAGCGAGCCAAA
                 GATCTTGAAGAAGAACTTGAGAGAACTATTCTTTTTTATCAAGGGAAGATTATATACC
                 ATGAGAAAAAAGCACATGATAATTGTTTGGCAGCATGGACTGCTGAAAGAAACCTCAA
                 TGATTTAAGGAAAGAAAATGCTCACAAAAGACAAAAATTAGCTGAAACAGAGTTTAAA
                 ATTAAACTTTTAGAAAAAGATCCTTATGCACTTGATGTTCCAAATACAGCATTTGGCA
                 GAGAGCATTCCTCATATGGTCCCTCACCATTGGGTCGGCCTTCATCTGAAACGAGAGC
                 TTTTCTCTATCTTCCGACTTTGTTGGAGGGTCCACTGAGACTCTCACCTTTGCTTCCA
                 GGGGGAGGAGGAAGAGACCCAAGAGGCCCAGGGAATCCTCTGGACCACCAGATTACCA
                 AGGAAAGAGGAGAATCAAGCTGTGATAGGTTTACTGATCCTCACAAGGCTCCTTCTGA
                 CACTGGGCCCCTGTCACCTCCGTGGGAACAGGACCGTAGGATGATGTTTCCTCCACCA
                 GGACAATCATATCCTGATTCAGCTCTTCCTCCACAAAGGCAAGACAGATTTTATTCTA
                 ATTCTGCTAGACGCTCTGGACTAGCAGAACTCAGAAGTTTTAATATACCTTCTTTGGA
                 TAAAATGGATGGGTCAATGCCTTCAGAAATGGAATCCAGTGGAAATGATACCAAAGAT
                 AATCTTGGTAATTTAAATGTGGCTGATTCATCTCTCCCTGCTGGAAATGAAGTGAGTG
                 GCCCTGGCTTTGTTCCTCCACCTCTTGCTTCAATCAGAGGTCCATTGTTTCCAGTGGA
                 TACGAGGGGCCCGTTCATGAGAAGAGGACCTCCTTTCCCTCCACCTCCTCCAGGAACC
                 ATGTTTGGAGCTTCTCCAGATTATTTTCCACCAAGGGATGTCCCAGGTCCACCACGTG
                 CTCCATTTGCAATGAGAAATGTCTGTCCACCGAGGGGTTTTCCTCCTTACCTTCCCCC
                 AAGACCTGGATTTTGCCCCCACCCCCACCCCCACAGTGAGTTCCCTTTAGGGTTGAGT
                 CTGCCTTCAAATGAGCCTGCTGCTGAAGATCCAGAACCACGGCAAGAAACCTGATAAT
                 ATTTTTGCTGTCTTCAAAAGTCATTTTGACTATTCTCATTTTCAGTTGAAGTAACTGC
                 TGTTACTTCAGTGATTACACTTTTGCTCAAATTGAA
                 ORF Start: ATG at 94 ORF Stop: TGA at 2488
                 SEQ ID NO:54         798 aa MW at 90383.6 kD
NOV20a,          MEEPRATPQLYLGLVLQLLPRVMAALPEGVRPNSNPYGFPWELVICAAVLGFVAVPFF
CG105463-01      LWRSFRSVRSRLYVGREKELAIALSGLIEEKCRLLEKFSLVQKEYEGYEVESSLEDAS
Protein Sequence FEKEATEAQSLEANCEKLNRSNSELEHEILCLEKGIKEEKSKHSEQDEVMADISKKIQ
                 SLEDESKSLKSLLTEAKMTFKGFQMNEEKLEIGIQDASSENCQLQESQKQLLQEAEVW
                 KEQVSELNKQKITFEDSKVHAEQVLNDKENHIETLTERLLKIKDQAAVLEEDITDDGN
                 LELEMNSELKDGAYLDNPPKGALKKLIHAAKLNASLTTLEGERNQFIFSYLKLIKPRK
                 SLESILKIFRRNKHLCSRKTHILKVRIRNFNRKLMTELYQENEMKLYRKLIVEENNRL
                 EKEKLSKVDEMISHATEELETCRKRAKDLEEELERTILFYQGKIIYHEKKAHDNCLAA
                 WTAERNLNDLRKENAHKRQKLAETEFKIKLLEKDPYALDVPNTAFGREHSSYGPSPLG
                 RPSSETRAFLYLPTLLEGPLRLSPLLPGGGGRDPRGPGNPLDHQITKERGESSCDRFT
                 DPHKAPSDTGPLSPPWEQDRRMMFPPPGQSYPDSALPPQRQDRFYSNSARRSGLAELR
                 SFNIPSLDKMDGSMPSEMESSGNDTKDNLGNLNVADSSLPAGNEVSGPGFVPPPLASI
                 RGPLFPVDTRGPFMRRGPPFPPPPPGTMFGASPDYFPPRDVPGPPRAPFAMRNVCPPR
                 GFPPYLPPRPGFCPHPHPHSEFPLGLSLPSNEPAAEDPEPRQET
                 SEQ ID NO:55         2483 bp
NOV20b,          AGCTGGAATTCGCCCTTCTCGACAGGCCATGGTTACTTTGGCCACTGCCAGAGCAGCC
CG105463-02      TTGGCACTATGGAGGAGCCTAGGGCTACCCCTCAGCTGTACTTGGGGCTGGTCCTGCA
DNA Sequence     GTTGCTACCCAGGGTTATGGCAGCACTGCCTGAAGGTGTGAGACCAAATTCGAATCCT
                 TATGGTTTTCCATGGGAATTGGTGATATGTGCAGCTGTCCTTGGATTTGTTGCTGTTC
                 CCTTTTTTTTGTGGAGAAGTTTTAGATCGGTTAGGAGTCGGCTTTATGTGGGAAGAGA
                 GAAAGAGCTTGCTATAGCGCTTTCTGGACTAATTGAAGAAAAATGTAGACTACTTGAA
                 AAATTTAGCCTTGTTCAAAAAGAGTATGAAGGCTATGAAGTAGAGTCATCTTTAGAGG
                 ATGCCAGCTTTGAGAAGGAGGCAACAGAAGCACAAAGTCTGGAGGCAAACTGTGAAAA
                 GCTGAACAGGTCCAATTCTGAACTGGAGCATGAAATACTCTGTCTAGAAAAGGGGATA
                 AAAGAAGAGAAATCTAAACATTCTGAACAAGATGAGGTGATGGCAGATATTTCCAAAA
                 AGATACAGTCTCTAGAAGATGAGTCAAAATCCCTCAAATCACTACTAACTGAAGCTAA
                 AATGACCTTCAAGGGATTTCAAATGAATGAAGAAAAACTGGAGATAGGAATACAAGAT
                 GCTTCGAGTGAAAATTGTCAACTTCAGGAAAGCCAGAAACAGCTTTTGCAAGAAGCTG
                 AAGTATGGAAAGAACAAGTGAGTGAACTTAATAAACAGAAAATAACATTTGAAGACTC
                 CAAAGTACACGCAGAACAAGTTCTAAATGATAAAGAAAATCACATCGAGACTCTGACT
                 GAACGCTTGCTAAAGATCAAAGATCAGGCTGCTGTGCTGGAAGAAGACATAACGGATG
                 ATGGTAACTTGGAATTAGAAATGAACAGTGAATTGAAAGATGGTGCTTACTTAGATAA
                 TCCTCCAAAAGGAGCTTTGAAGAAACTGATTCATGCTGCTAAGTTAAATGCTTCTTTA
                 ACAACCTTAGAAGGAGAAAGAAACCAATTTATATTCAGTTATCTGAAGTTGATAAAAC
                 CAAGGAAGAGCTTAGAGAGCATATTAAAAATCTTCAGACGGAACAAGCATCTTTGCAG
                 TCGGAAAACACACATTTTGAAAGTGAGAATCAGAAACTTCAACAGAAAGTTAATGACT
                 GAGTTATATCAAGAAAATGAAATGAAACTCTACAGGAAATTAATAGTAGAGGAAAATA
                 ACCGGTTAGAGAAAGAGAAACTTTCTAAAGTAGACGAAATGATCAGCCATGCCACTGA
                 AGAGCTGGAGACCTGCAGAAAGCGAGCCAAAGATCTTGAAGAAGAACTTGAGAGAACT
                 ATTCTTTTTTATCAAGGGAAGATTATATACCATGAGAAAAAAGCACATGATAATTGTT
                 TGGCAGCATGGACTGCTGAAAGAAACCTCAATGATTTAAGGAAAGAAAATGCTCACAA
                 AAGACAAAAATTAGCTGAAACAGAGTTTAAAATTAAACTTTTAGAAAAAGATCCTTAT
                 GCACTTGATGTTCCAAATACAGCATTTGGCAGAGAGCATTCCTCATATGGTCCCTCAC
                 CATTGGGTCGGCCTTCATCTGAAACGAGAGCTTTTCTCTATCTTCCGACTTTGTTGGA
                 GGGTCCACTGAGACTCTCACCTTTGCTTCCAGGGGGAGGAGGAAGAGGCCCAAGAGGC
                 CCAGGGAATCCTCTGGACCACCAGATTACCAAGGAAAGAGGAGAATCAAGCTGTGATA
                 GGTTTACTGATCCTCACAAGGCTCCTTCTGACACTGGGCCCCTGTCACCTCCGTGGGA
                 ACAGGACCGTAGGATGATGTTTCCTCCACCAGGACAATCATATCCTGATTCAGCTCTT
                 CCTCCACAAAGGCAAGACAGATTTTATTCTAATTCTGCTAGACGCTCTGGACTAGCAG
                 AACTCAGAAGTTTTAATATACCTTCTTTGGATAAAATGGATGGGTCAATGCCTTCAGA
                 AATGGAATCCAGTGGAAATGATACCAAAGATAATCTTGGTAATTTAAATGTGGCTGAT
                 TCATCTCTCCCTGCTGGAAATGAAGTGAGTGGCCCTGGCTTTGTTCCTCCACCTCTTG
                 CTCCAATCAGAGGTCCGTTGTTTCCAGTGGATACGAGGGGCCCGTTCATGAGAAGAGG
                 ACCTCCTTTCCCTCCACCTCCTCCAGGAACCATGTTTGGAGCTTCTCCAGATTATTTT
                 CCACCAAGGGATGTCCCAGGTCTACCACGTGCTCCATTTGCAATGAGAAATGTCTGTC
                 CACCGAGGGGTTTTCCTCCTTACCTTCCCCCAAGACCTGGATTTTGCCCCCACCCCCA
                 CCCCCACATTCTGAAGATAGAGTGAGTTCCCTTTAGGGTTGAGTGCCTTCAATGAGC
                 CTGCTGCTGAAGATCCAGAACCACGGCAAGAAACCTGATAATATTTT
                 ORF Start: ATG at 67 ORF Stop: TGA at 2401
                 SEQ ID NO:56         778 aa MW at 88255.5 kD
NOV20b,          MEEPRATPQLYLGLVLQLLPRVMAALPEGVRPNSNPYGFPWELVICAAVLGFVAVPFF
CG105463-02      LWRSFRSVRSRLYVGREKELAIALSGLIEEKCRLLEKFSLVQKEYEGYEVESSLEDAS
Protein Sequence FEKEATEAQSLEANCEKLNRSNSELEHEILCLEKGIKEEKSKHSEQDEVMADISKKIQ
                 SLEDESKSLKSLLTEAKMTFKGFQMNEEKLEIGIQDASSENCQLQESQKQLLQEAEVW
                 KEQVSELNKQKITFEDSKVHAEQVLNDKENHIETLTERLLKIKDQAAVLEEDITDDGN
                 LELEMNSELKDGAYLDNPPKGALKKLIHAAKLNASLTTLEGERNQFIFSYLKLIKPRK
                 SLESILKIFRRNKHLCSRKTHILKVRIRNFNRKLMTELYQENEMKLYRKLIVEENNRL
                 EKEKLSKVDEMISHATEELETCRKRAKDLEEELERTILFYQGKIIYHEKKAHDNCLAA
                 WTAERNLNDLRKENAHKRQKLAETEFKIKLLEKDPYALDVPNTAFGREHSSYGPSPLG
                 RPSSETRAFLYLPTLLEGPLRLSPLLPGGGGRGPRGPGNPLDHQITKERGESSCDRFT
                 DPHKAPSDTGPLSPPWEQDRRMMFPPPGQSYPDSALPPQRQDRFYSNSARRSGLAELR
                 SFNIPSLDKMDGSMPSEMESSGNDTKDNLGNLNVADSSLPAGNEVSGPGFVPPPLAPI
                 RGPLFPVDTRGPFMRRGPPFPPPPPGTMFGASPDYFPPRDVPGLPRAPFAMRNVCPPR
                 GFPPYLPPRPGFCPHPHPHILKIE

[0412] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 20B.

TABLE 20B
Comparison of NOV20a against NOV20b.
	NOV20a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV20b	1 . . . 750	662/750 (88%)
	1 . . . 750	662/750 (88%)

[0413] Further analysis of the NOV20a protein yielded the following properties shown in Table 20C.

TABLE 20C
Protein Sequence Properties NOV20a
PSort     0.4600 probability located in plasma membrane;
analysis: 0.1000 probability located in
          endoplasmic reticulum (membrane);
          0.1000 probability located in
          endoplasmic reticulum (lumen);
          0.1000 probability located in outside
SignalP   Cleavage site between residues 25 and 26
analysis:

[0414] A search of the NOV20a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 20D.

TABLE 20D
Geneseq Results for NOV20a
		NOV20a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAY77574	Human cytoskeletal protein	1 . . . 798	638/812 (78%)	0.0
	(HCYT) (clone 3768043) - Homo	1 . . . 806	683/812 (83%)
	sapiens, 806 aa. [WO200006730-
	A2, 10-FEB-2000]
ABG05280	Novel human diagnostic protein	1 . . . 797	639/814 (78%)	0.0
	#5271 - Homo sapiens, 881 aa.	59 . . . 867	684/814 (83%)
	[WO200175067-A2, 11-OCT-2001]
ABG05280	Novel human diagnostic protein	1 . . . 797	639/814 (78%)	0.0
	#5271 - Homo sapiens, 881 aa.	59 . . . 867	684/814 (83%)
	[WO200175067-A2, 11-OCT-2001]
ABG20258	Novel human diagnostic protein	1 . . . 797	634/814 (77%)	0.0
	#20249 - Homo sapiens, 881 aa.	59 . . . 867	681/814 (82%)
	[WO200175067-A2, 11-OCT-2001]
ABG20258	Novel human diagnostic protein	1 . . . 797	634/814 (77%)	0.0
	#20249 - Homo sapiens, 881 aa.	59 . . . 867	681/814 (82%)
	[WO200175067-A2, 11-OCT-2001]

[0415] In a BLAST search of public sequence databases, the NOV20a protein was found to have homology to the proteins shown in the BLASTP data in Table 20E.

TABLE 20E
Public BLASTP Results for NOV20a
		NOV20a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O15320	Meningioma-expressed antigen 6/11	1 . . . 798	653/810 (80%)	0.0
	(MEA6) (MEA11) - Homo sapiens	1 . . . 804	696/810 (85%)
	(Human), 804 aa.
Q96SG9	BA500G10.2 (NOVEL PROTEIN	1 . . . 798	616/805 (76%)	0.0
	SIMILAR TO MENINGIOMA	15 . . . 816	670/805 (82%)
	EXPRESSED ANTIGEN 6 (MEA6)
	AND 11 (MEA11)) - Homo sapiens
	(Human), 825 aa (fragment).
Q96RT6	CTAGE-2 - Homo sapiens (Human),	30 . . . 775	605/749 (80%)	0.0
	754 aa.	1 . . . 746	642/749 (84%)
O95046	WUGSC: H_DJ0988G15.3	1 . . . 770	570/775 (73%)	0.0
	PROTEIN (DJ1005H11.2)	1 . . . 775	633/775 (81%)
	(WUGSC: H_DJ0988G15.3
	PROTEIN) - Homo sapiens
	(Human), 777 aa.
AAH26864	SIMILAR TO MENINGIOMA	30 . . . 796	520/783 (66%)	0.0
	EXPRESSED ANTIGEN 6	1 . . . 778	600/783 (76%)
	(COILED-COIL PROLINE-RICH) -
	Mus musculus (Mouse), 779 aa.

[0416] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20F.

TABLE 20F
Domain Analysis of NOV20a
		Identities/
Pfam		Similarities	Expect
Domain	NOV20a Match Region	for the Matched Region	Value
No Significant Matches Found

Example 21

[0417] The NOV21 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 21A.

TABLE 21A
NOV21 Sequence Analysis
                 SEQ ID NO:57         1269 bp
NOV21a,          AGCGGGGGGCGCTGCCTCGAGCCTCATGGCTGCCCCTGCTTCCGTCATGGGCCCACTC
CG105491-01      GGGCCCTCTGCCCTGGGCCTTCTGCTGCTGCTCCTGGTGGTGGCCCCTCCCCGGGTCG
DNA Sequence     CAGCATTGGTCCACAGACAGCCAGAGAACCAGGGAATCTCCCTAACTGGCAGCGTGGC
                 CTGTGGTCGGCCCAGCATGGAGGGGAAAATCCTGGGCGGCGTCCCTGCGCCCGAGAGG
                 AAGTGGCCGTGGCAGGTCAGCGTGCACTACGCAGGCCTCCACGTCTGCGGCGGCTCCA
                 TCCTCAATGAGTACTGGGTGCTGTCAGCTGCGCACTGCTTTCACAGGGACAAGAATAT
                 CAAAATCTATGACATGTACGTAGGCCTCGTAAACCTCAGGGTGGCCGGCAACCACACC
                 CAGTGGTATGAGGTGAACAGGGTGATCCTGCACCCCACATATGAGATGTACCACCCCA
                 TCGGAGGTGACGTGGCCCTGGTGCAGCTGAAGACCCGCATTGTGTTTTCTGAGTCCGT
                 GCTCCCGGTTTGCCTTGCAACTCCAGAAGTGAACCTTACCAGTGCCAATTGCTGGGCT
                 ACGGGATGGGGACTAGTCTCAAAACAAGGTGAGACCTCAGACGAGCTGCAGGAGGTGC
                 AGCTCCCGCTGATCCTGGAGCCCTGGTGCCACCTGCTCTACGGACACATGTCCTACAT
                 CATGCCCGACATGCTGTGTGCTGGGGACATCCTGAATGCTAAGACCGTGTGTGAGGGC
                 GACTCCGGGGGCCCACTTGTCTGTGAATTCAACCGCAGCTGGTTGCAGATTGGAATTG
                 TGAGCTGGGGCCGAGGCTGCTCCAACCCTCTGTACCCTGGAGTGTATGCCAGTGTTTC
                 CTATTTCTCAAAATGGATATGTGATAACATAGAAATCACGCCCACTCCTGCTCAGCCA
                 GCCCCTGCTCTCTCTCCAGCTCTGGGGCCCACTCTCAGCGTCCTAATGGCCATGCTGG
                 CTGGCTGGTCAGTGCTGTGAGGTCAGGATACCCACTCTAGGATTCTCATGGCTGCACA
                 CCCTGCCCCAGCCCAGCTGCCTCCAGACCCCTAAGCATCTCCTGTCCTGGCCTCTCTG
                 AAGCAGACAAGGGCCACCTATCCCGGGGGTGGATGCTGAGTCCAGGAGGTGATGAGCA
                 AGTGTACAAAAGAAAAAAGGGAAGGGGGAGAGGGGCTGGTCAGGGAGAACCCAGCTTG
                 GGCAGAGTGCACCTGAGATTTGATAAGATCATTAAATATTTACAAAGCAAA
                 ORF Start: ATG at 26 ORF Stop: TGA at 1004
                 SEQ ID NO:58         326 aa MW at 35323.8 kD
NOV21a,          MAAPASVMGPLGPSALGLLLLLLVVAPPRVAALVHRQPENQGISLTGSVACGRPSMEG
CG105491-01      KILGGVPAPERKWPWQVSVHYAGLHVCGGSILNEYWVLSAAHCFHRDKNIKIYDMYVG
Protein Sequence LVNLRVAGNHTQWYEVNRVILHPTYEMYHPIGGDVALVQLKTRIVFSESVLPVCLATP
                 EVNLTSANCWATGWGLVSKQGETSDELQEVQLPLILEPWCHLLYGHMSYIMPDMLCAG
                 DILNAKTVCEGDSGGPLVCEFNRSWLQIGIVSWGRGCSNPLYPGVYASVSYFSKWICD
                 NIEITPTPAQPAPALSPALGPTLSVLMAMLAGWSVL

[0418] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.

TABLE 21B
Protein Sequence Properties NOV21a
PSort     0.7900 probability located in plasma membrane;
analysis: 0.3000 probability located in Golgi body;
          0.2000 probability located in endoplasmic
          reticulum (membrane);
          0.1007 probability located in microbody (peroxisome)
SignalP   Cleavage site between residues 33 and 34
analysis:

[0419] A search of the NOV21a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 21C.

TABLE 21C
Geneseq Results for NOV21a
		NOV21a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAU82747	Amino acid sequence of novel	1 . . . 326	326/326 (100%)	0.0
	human protease #46 - Homo	1 . . . 326	326/326 (100%)
	sapiens, 326 aa. [WO200200860-
	A2, 03-JAN-2002]
AAB73945	Human protease T - Homo sapiens,	13 . . . 288	115/286 (40%)	6e−53
	290 aa. [WO200116293-A2,	4 . . . 272	152/286 (52%)
	08-MAR-2001]
AAE03821	Human gene 4 encoded secreted	13 . . . 288	115/286 (40%)	6e−53
	protein HWHIH10, SEQ ID NO: 67 -	4 . . . 272	152/286 (52%)
	Homo sapiens, 290 aa.
	[WO200136440-A1, 25-MAY-2001]
AAU12282	Human PRO4327 polypeptide	13 . . . 288	115/286 (40%)	6e−53
	sequence - Homo sapiens, 290 aa.	4 . . . 272	152/286 (52%)
	[WO200140466-A2, 07-JUN-2001]
AAY73388	HTRM clone 3376404 protein	13 . . . 288	115/286 (40%)	6e−53
	sequence - Homo sapiens, 290 aa.	4 . . . 272	152/286 (52%)
	[WO9957144-A2, 11-NOV-1999]

[0420] In a BLAST search of public sequence databases, the NOV21a protein was found to have homology to the proteins shown in the BLASTP data in Table 21D.

TABLE 21D
Public BLASTP Results for NOV21a
		NOV21a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9BQR3	Marapsin precursor (EC 3.4.21.—) -	13 . . . 288	115/286 (40%)	1e−52
	Homo sapiens (Human), 290 aa.	4 . . . 272	152/286 (52%)
Q9PVX7	EPIDERMIS SPECIFIC SERINE	50 . . . 314	98/275 (35%)	5e−52
	PROTEASE - Xenopus laevis	16 . . . 287	159/275 (57%)
	(African clawed frog), 389 aa.
AAH24903	RIKEN CDNA 2010001P08	51 . . . 326	114/288 (39%)	2e−51
	GENE - Mus musculus (Mouse),	45 . . . 329	158/288 (54%)
	331 aa.
Q91XC4	SIMILAR TO DISTAL	51 . . . 288	106/247 (42%)	6e−51
	INTESTINAL SERINE	28 . . . 272	138/247 (54%)
	PROTEASE - Mus musculus
	(Mouse), 310 aa.
Q9QYZ9	DISTAL INTESTINAL SERINE	51 . . . 288	105/247 (42%)	7e−50
	PROTEASE - Mus musculus	28 . . . 272	137/247 (54%)
	(Mouse), 310 aa.

[0421] PFam analysis predicts that the NOV21a protein contains the domains shown in the Table 21E.

TABLE 21E
Domain Analysis of NOV21a
		Identities/
Pfam		Similarities	Expect
Domain	NOV21a Match Region	for the Matched Region	Value
trypsin	60 . . . 288	87/265 (33%)	5.3e−72
		172/265 (65%)

Example 22

[0422] The NOV22 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 22A.

TABLE 22A
NOV22 Sequence Analysis
	SEQ ID NO: 59	4131bp
NOV22a,	GTGCCGAGGATGGCCAGGCAGCCACCGCCGCCCTGGATCCATGCAGCCTTCCTCCTCT
CG105954-01
DNA Sequence	GCCTCCTCAGTCTTGGCGGAGCCATCGAAATTCCTATGGTTCCAAGCATTCAGAATGA
	GCTGACGCAGCCGCCAACCATCACCAAGCAGTCAGCGAAGGATCACATCGTGGACCCC
	CGTGATAACATCCTGATTGAGTGTGAAGCAAAAGGGAACCCTGCCCCCAGCTTCCACT
	GGACACGAAACAGCAGATTCTTCAACATCGCCAAGGACCCCCGGGTGTCCATGAGGAG
	GAGGTCTGGGACCCTGGTGATTGACTTCCGCAGTGGCGGGCGGCCGGAGGAATATGAG
	GGGGAATATCAGTGCTTCGCCCGCAACAAATTTGGCACGGCCCTGTCCAATAGGATCC
	GCCTGCAGGTGTCTAAATCTCCTCTGTGGCCCAAGGAAAACCTAGACCCTGTCGTGGT
	CCAAGAGGGCGCTCCTTTGACGCTCCAGTGCAACCCCCCGCCTGGACTTCCATCCCCG
	GTCATCTTCTGGATGAGCAGCGCCATGGAGCCCATCACCCAAGACAAACGTGTCTCTC
	AGGGCCATAACGGAGACCTATACTTCTCCAACGTGATGCTGCAGGACATGCAGACCGA
	CTACAGTTGTAACGCCCGCTTCCACTTCACCCACACCATCCAGCAGAAGAACCCTTTC
	ACCCTCAAGGTCCTCACCAGTAAGCCTTATAATGACTCGTCCTTAAGAAACCACCCTG
	ACATGTACAGTGCCCGAGGAGTTGCAGAAAGAACACCAAGCTTCATGTATCCCCAGGG
	CACCGCGAGCAGCCAGATGGTGCTTCGTGGCATGGACCTCCTGCTGGAATGCATCGCC
	TCCGGGGTCCCAACACCAGACATCGCATGGTACAAGAAAGGTGGGGACCTCCCATCTG
	ATAAGGCCAAGTTTGAGAACTTTAATAAGGCCCTGCGTATCACAAATGTCTCTGAGGA
	AGACTCCGGGGAGTATTTCTGCCTGGCCTCCAACAAGATGGGCAGCATCCGGCACACG
	ATCTCGGTGAGAGTAAAGGCTGCTCCCTACTGGCTGGACGAACCCAAGAACCTTATTC
	TGGCTCCTGGCGAGGATGGGAGACTGGTGTGTCGAGCCAATGGAAACCCCAAACCCAC
	TGTCCAGTGGATGGTGAATGGGGAACCTTTGCAAGCGGCACCACCTAACCCAAACCGT
	GAGGTGGCCGGAGACACCATCATCTTCCGGGACACCCAGATCAGCAGCAGGGCTGTGT
	ACCAGTGCAACACCTCCAACGAGCATGGCTACCTGCTGGCCAACGCCTTTGTCAGTGT
	GCTGGATGTGCCGCCTCGGATGCTGTCGCCCCGGAACCAGCTCATTCGAGTGATTCTT
	TACAACCGGACGCGGCTGGACTGCCCTTTCTTTGGGTCTCCCATCCCCACACTGCGAT
	GGTTTAAGAATGGGCAAGGAAGCAACCTGGATGGTGGCAACTACCATGTTTATGAGAA
	CGGCAGTCTGGAAATTAAGATGATCCGCAAAGAGGACCAGGGCATCTACACCTGTGTC
	GCCACCAACATCCTGGGCAAAGCTGAAAACCAAGTCCGCCTGGAGGTAAAAGACCCCA
	CCAGGATCTACCGGATGCCCGAGGACCAGGTGGCCAGAAGGGGCACCACGGTGCAACT
	GGAGTGTCGGGTGAAGCACGACCCCTCCCTGAAACTCACCGTCTACTGGCTGAAGGAT
	GACGAGCCGCTCTATATTGGAAACAGGATGAAGAAGGAAGACGACTCCCTGACCATCT
	TTGGGGTGGCAGAGCGGGACCAGGGCAGTTACACGTGTGTCGCCAGCACCGAGCTAGA
	CCAAGACCTGGCCAAGGCCTACCTCACCGTGCTAGGACGGCCAGACCGGCCCCGGGAC
	CTGGAGCTGACCGACCTGGCCGAGAGGAGCGTGCGGCTGACCTGGATCCCCGGGGATG
	CTAACAACAGCCCCATCACAGACTACGTCGTCCAGTTTGAAGAAGACCAGTTCCAACC
	TGGGGTCTGGCATGACCATTCCAAGTACCCCGGCAGCGTTAACTCAGCCGTCCTCCGG
	CTGTCCCCGTATGTCAACTACCAGTTCCGTGTCATTGCCATCAACGAGGTTGGGAGCA
	GCCACCCCAGCCTCCCATCCGAGCGCTACCGAACCAGTGGAGCACCCCCCGAGTCCAA
	TCCTGGTGACGTGAAGGGAGAGGGGACCAGAAAGAACAACATGGAGATCACGTGGACG
	CCCATGAATGCCACCTCGGCCTTTGGCCCCAACCTGCGCTACATTGTCAAGTGGAGGC
	GGAGAGAGACTCGAGAGGCCTGGAACAACGTCACAGTGTGGGGCTCTCGCTACGTGGT
	GGGGCAGACCCCAGTCTACGTGCCCTATGAGATCCGAGTCCAGGCTGAAAATGACTTC
	GGGAAGGGCCCTGAGCCAGAGTCCGTCATCGGTTACTCCGGAGAAGATTATCCCAGGG
	CTGCGCCCACTGAAGTTAAAGTCCGAGTCATGAACAGCACAGCCATCAGCCTTCAGTG
	GAACCGCGTCTACTCCGACACGGTCCAGGGCCAGCTCAGAGAGTACCGAGCCTACTAC
	TGGAGGGAGAGCAGCTTGCTGAAGAACCTGTGGGTGTCTCAGAAGAGACAGCAAGCCA
	GCTTCCCTGGTGACCGCCTCCGTGGCGTGGTGTCCCGCCTCTTCCCCTACAGTAACTA
	CAAGCTGGAGATGGTTGTGGTCAATGGGAGAGGTGATGGGCCTCGCAGTGAGACCAAG
	GAGTTCACCACCCCGGAAGGAGTACCCAGTGCCCCTAGGCGTTTCCGAGTCCGGCAGC
	CCAACCTGGAGACAATCAACCTGGAATGGGATCATCCTGAGCATCCAAATGGGATCAT
	GATTGGATACACTCTCAAATATGTGGCCTGTACGTTCTCCCCAGTTAACGGGACCAAA
	GTAGGAAAGCAGATAGTGGAAAACTTCTCTCCCAATCAGACCAAGTTCACGGTGCAAA
	GAACGGACCCCGTGTCACGCTACCGCTTTACCCTCAGCGCCAGGACGCAGGTGGGCTC
	TGGGGAAGCCGTCACAGAGGAGTCACCAGCACCCCCGAATGAAGGTAGGTGCATGGCA
	GCAGCCCCTGGGGTAAAACCCCCGACTACCGTGGGTGCGACGGGCGCTGTGAGCAGTA
	CCGATGCTACTGCCATTGCTGCCACCACCGAAGCCACAACAGTCCCCATCATCCCAAC
	TGTCGCACCTACCACCATGGCCACCACCACCACCGTCGCCACAACTACTACAACCACT
	GCTGCCGCCACCACCACCACGGAGAGTCCTCCCACCACCACCTCCGGGACTAAGATAC
	ACGAATCCGGTACTGCGCATCGCCCATGCTCCCCAGCCCCTGATGAGCAGTCCATATG
	GAACGTCACGGTGCTCCCCAACAGTAAATGGGCCAACATCACCTGGAAGCACAATTTC
	GGGCCCGGAACTGACTTTGTGGTTGAGTACATCGACAGTAACCATACGAAAAAAACTG
	TCCCAGTTAAGGCCCAGGCTCAGCCTATACAGCTGACAGACCTCTATCCCGGGATGAC
	ATACACGTTGCGGGTTTATTCCCGGGACAACGAGGGCATCAGCAATCATTCACGGGTT
	TGCTTCCGGCCCTCCCCGCCAGCTTACACCAACAACCAAGCGGACATCGCCACCCAGG
	GCTGGTTCATTGGGCTTATGTGCGCCATCGCCCTCCTGGTGCTGATCCTGCTCATCGT
	CTGTTTCATCAAGAGGAGTCGCGGCGGCAAGTACCCAGTACGAGAAAAGAAGGATGTT
	CCCCTTGGCCCTGAAGACCCCAAGGAAGAGGATGGCTCATTTGACTATAGGTCTTTGG
	CCAGTGATGAGGACAACAAGCCCCTGCAGGGCAGTCAGACATCTCTGGACGGCACCAT
	CAAGCAGCAGGAGAGTGACGACAGCCTGGTGGACTATGGCGAGGGTGGCGAGGGTCAG
	TTCAATGAAGACGGCTCCTTCATCGGCCAGTACACGGTCAAAAAGGACAAGGAGGAAA
	CAGAGGGCAACGAAAGCTCAGAGGCCACGTCACCTGTCAATGCTATCTACTCTCTGGC
	CTAACGGAGCCCA
	ORF Start: ATG at 10		ORF Stop: TAA at 4120
	SEQ ID NO: 60	1370 aa	MW at 152752.5kD
NOV22a,	MARQPPPPWIHAAFLLCLLSLGGAIEIPMVPSIQNELTQPPTITKQSAKDHIVDPRDN
CG105954-01
Protein Sequence	ILIECEAKGNPAPSFHWTRNSRFFNIAKDPRVSMRRRSGTLVIDFRSGGRPEEYEGEY
	QCFARNKFGTALSNRIRLQVSKSPLWPKENLDPVVVQEGAPLTLQCNPPPGLPSPVIF
	WMSSAMEPITQDKRVSQGHNGDLYFSNVMLQDMQTDYSCNARFHFTHTIQQKNPFTLK
	VLTSKPYNDSSLRNHPDMYSARGVAERTPSFMYPQGTASSQMVLRGMDLLLECIASGV
	PTPDIAWYKKGGDLPSDKAKFENFNKALRITNVSEEDSGEYFCLASNKMGSIRHTISV
	RVKAAPYWLDEPKNLILAPGEDGRLVCRANGNPKPTVQWMVNGEPLQAAPPNPNREVA
	GDTIIFRDTQISSRAVYQCNTSNEHGYLLANAFVSVLDVPPRMLSPRNQLIRVILYNR
	TRLDCPFFGSPIPTLRWFKNGQGSNLDGGNYHVYENGSLEIKMIRKEDQGIYTCVATN
	ILGKAENQVRLEVKDPTRIYRMPEDQVARRGTTVQLECRVKHDPSLKLTVYWLKDDEP
	LYIGNRMKKEDDSLTIFGVAERDQGSYTCVASTELDQDLAKAYLTVLGRPDRPRDLEL
	TDLAERSVRLTWIPGDANNSPITDYVVQFEEDQFQPGVWHDHSKYPGSVNSAVLRLSP
	YVNYQFRVIAINEVGSSHPSLPSERYRTSGAPPESNPGDVKGEGTRKNNMEITWTPMN
	ATSAFGPNLRYIVKWRRRETREAWNNVTVWGSRYVVGQTPVYVPYEIRVQAENDFGKG
	PEPESVIGYSGEDYPRAAPTEVKVRVMNSTAISLQWNRVYSDTVQGQLREYRAYYWRE
	SSLLKNLWVSQKRQQASFPGDRLRGVVSRLFPYSNYKLEMVVVNGRGDGPRSETKEFT
	TPEGVPSAPRRFRVRQPNLETINLEWDHPEHPNGIMIGYTLKYVACTFSPVNGTKVGK
	QIVENFSPNQTKFTVQRTDPVSRYRFTLSARTQVGSGEAVTEESPAPPNEGRCMAAAP
	GVKPPTTVGATGAVSSTDATAIAATTEATTVPIIPTVAPTTMATTTTVATTTTTTAAA
	TTTTESPPTTTSGTKIHESGTAHRPCSPAPDEQSIWNVTVLPNSKWANITWKHNFGPG
	TDFVVEYIDSNHTKKTVPVKAQAQPIQLTDLYPGMTYTLRVYSRDNEGISNHSRVCFR
	PSPPAYTNNQADIATQGWFIGLMCAIALLVLILLIVCFIKRSRGGKYPVREKKDVPLG
	DGSFIGQYTVKKDKEETEGNESSEATSPVNAIYSLA

[0423] Further analysis of the NOV22a protein yielded the following properties shown in Table 22B.

TABLE 22B
Protein Sequence Properties NOV22a
PSort     0.4600 probability located in plasma membrane;
analysis: 0.1000 probability located in endoplasmic
          reticulum (membrane);
          0.1000 probability located in endoplasmic reticulum (lumen);
          0.1000 probability located in outside
SignalP   Cleavage site between residues 25 and 26
analysis:

[0424] A search of the NOV22a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 22C.

TABLE 22C
Geneseq Results for NOV22a
		NOV22a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM78714	Human protein SEQ ID NO 1376 -	92 . . . 1050	928/959 (96%)	0.0
	Homo sapiens, 937 aa.	1 . . . 937	933/959 (96%)
	[WO200157190-A2, 09-AUG-2001]
AAM78715	Human protein SEQ ID NO 1377 -	92 . . . 1050	928/974 (95%)	0.0
	Homo sapiens, 952 aa.	1 . . . 952	933/974 (95%)
	[WO200157190-A2, 09-AUG-2001]
AAW59994	Human neural cell adhesion	15 . . . 1072	517/1075 (48%)	0.0
	molecule splice variant NrCAMvar -	20 . . . 1082	708/1075 (65%)
	Homo sapiens, 1304 aa.
	[WO9836062-A1, 20-AUG-1998]
AAU10650	Chicken Nr-CAM protein sequence -	12 . . . 1054	508/1055 (48%)	0.0
	Gallus sp, 1268 aa. [US6313265-	12 . . . 1042	696/1055 (65%)
	B1, 06-NOV-2001]
AAB90717	Human CO722_1 protein sequence	15 . . . 1060	509/1058 (48%)	0.0
	SEQ ID 130 - Homo sapiens, 1192	20 . . . 1047	701/1058 (66%)
	aa. [WO200119988-A1, 22-MAR-2001]

[0425] In a BLAST search of public sequence databases, the NOV22a protein was found to have homology to the proteins shown in the BLASTP data in Table 22D.

TABLE 22D
Public BLASTP Results for NOV22a
		NOV22a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
O42414	NEUROFASCIN PRECURSOR -	13 . . . 1370	1026/1372 (74%)	0.0
	Gallus gallus (Chicken), 1369	14 . . . 1369	1148/1372 (82%)
	aa.
Q91Z60	NEUROFASCIN 155 KDA	1 . . . 1042	985/1042 (94%)	0.0
	ISOFORM - Rattus norvegicus	1 . . . 1031	1008/1042 (96%)
	(Rat), 1174 aa.
Q9QVN5	NEUROFASCIN ISOFORM -	25 . . . 1042	965/1019 (94%)	0.0
	Rattus sp, 1151 aa.	1 . . . 1008	987/1019 (96%)
Q90924	NEUROFASCIN PRECURSOR -	13 . . . 1114	844/1114 (75%)	0.0
	Gallus gallus (Chicken), 1272	14 . . . 1120	949/1114 (84%)
	aa.
O94856	KIAA0756 PROTEIN - Homo	193 . . . 1050	830/858 (96%)	0.0
	sapiens (Human), 836 aa	1 . . . 836	833/858 (96%)
	(fragment).

[0426] PFam analysis predicts that the NOV22a protein contains the domains shown in the Table 22E.

TABLE 22E
Domain Analysis of NOV22a
		Identities/
	NOV22a	Similarities for
Pfam Domain	Match Region	the Matched Region	Expect Value
ig	56 . . . 120	11/68	(16%)	0.032
		43/68	(63%)
ig	155 . . . 215	13/62	(21%)	0.01
		39/62	(63%)
ig	278 . . . 335	18/61	(30%)	4.3e−11
		44/61	(72%)
ig	368 . . . 427	13/63	(21%)	2.1e−05
		44/63	(70%)
ig	462 . . . 520	18/62	(29%)	1.1e−07
		45/62	(73%)
ig	553 . . . 611	19/60	(32%)	5.9e−09
		40/60	(67%)
fn3	630 . . . 716	28/88	(32%)	6.6e−14
		64/88	(73%)
fn3	729 . . . 815	27/92	(29%)	5.9e−07
		62/92	(67%)
fn3	827 . . . 922	24/97	(25%)	3.7e−07
		66/97	(68%)
fn3	934 . . . 1026	20/97	(21%)	2.1e−08
		66/97	(68%)
fn3	1134 . . . 1213	22/85	(26%)	1.5e−08
		56/85	(66%)

Example 23

[0427] The NOV23 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 23A.

TABLE 23A
NOV23 Sequence Analysis
	SEQ ID NO: 61	2497 bp
NOV23a,	GCCCCGATGGACGCCGCGTTCCTCCTCGTCCTCGGGCTGTTGGCCCAGAGCCTCTGCC
CG105963-01
DNA Sequence	TGTCTTTGGGGGTTCCTGGATGGAGGAGGCCCACCACCCTGTACCCCTGGCGCCGGGC
	GCCTGCCCTGAGCCGCGTGCGGAGGGCCTGGGTCATCCCCCCGATCAGCGTATCCGAG
	AACCACAAGCGTCTCCCCTACCCCCTGGTTCAGGTGAGCAGGTGGAAGCACCAGTTGG
	CCAGCGTCATCTCCAGCATCCAGGGCCCCGGCGTGGATGAGGAGCCCCGGGGCGTCTT
	CTCTATCGCCCAGTTCACAGGGAAGGTCTTCCTCAATGCCATGCTGGACCGCGAGAAG
	ACTGATCGCTTCAGGCTAAGAGGGTTTGCCCTGGACCTGGGAGGATCCACCCTGGAGG
	ACCCCACGGACCTGGAGATTGTAGTTGTGGATCAGAATGACAACCGGCCAGCCTTCCT
	GCAGGAGGCGTTCACTGGCCGCGTGCTGGAGGGTGCAGTCCCAGGTACCTATGTGACC
	AGGGCAGAGGCCACAGATGCCGACGACCCCGAGACGGACAACGCAGCGCTGCGGTTCT
	CCATCCTGCAGCAGGGCAGCCCCGAGCTCTTCAGCATCGACGAGCTCACAGGAGAGAT
	CCGCACAGTGCAAGTGGGGCTGGACCGCGAGGTGGTCGCGGTGTACAATCTGACCCTG
	CAGGTGGCGGACATGTCTGGAGACGGCCTCACAGCCACTGCTTCAGCCATCATCACCT
	TTGATGACATCAATGACAATGCCCCCGAGTTCACCAGGGATGAGTTCTTCATGGAGGC
	CATAGAGGCCGTCAGCGGAGTGGATGTGGGACGCCTGGAAGTGGAGGACAGGGACCTG
	CCAGGCTCCCCAAACTGGGTGGCCAGGTTCACCATCCTGGAAGGCGACCCCGATGGGC
	AGTTCACCATCCGCACGGACCCCAAGACCAACGAGGGTGTTCTGTCCATTGTGAAGGC
	CCTGGACTATGAAAGCTGTGAACACTACGAAACTAAAACACACGGGCAGGATAAGACA
	GAGAACGCACGGGCAGGGCTGAGGGCTGAGCGGGGCCAGGCCAAGGTCCGCGTGCATG
	TGCAGGACACCAACGAGCCCCCCGTGTTCCAGGAGAACCCACTTCGGACCAGCCTAGC
	AGAGGGGGCACCCCCAGGCACTCTGGTGGCCACCTTCTCTGCCCGGGACCCTGACACA
	GAGCAGCTGCAGAGGCTCAGCTACTCCAAGGACTACGACCCGGAAGACTGGCTGCAAG
	TGGACGCAGCCACTGGCCGGATCCAGACCCAGCACGTGCTCAGCCCGGCGTCCCCTTT
	CCTCAAGGGCGGCTGGTACAGAGCCATCGTCTTGGCCCAGGATGCCTCCCAGCCCCGC
	ACCGCCACCGGCACCCTGTCCATCGAGATCCTGGAGGTGAACGACCATGCACCTGTGC
	TGGCCCCGCCGCCGCCGGGCAGCCTGTGCAGCGAGCCACACCAAGGCCCAGGCCTCCT
	CCTGGGCGCCACGGATGAGGACCTGCCCCCCCACGGGGCCCCCTTCCACTTCCAGCTG
	AGCCCCAGGCTCCCAGAGCTCGGCCGGAACTGGAGCCTCAGCCAGGTCAACCCTCTCT
	CCCATCACCGTCTCCACCCAGACCCCCACCTGCCCCATGGCCCCCATTTCATGTCTGT
	GGCTCACCAGCTTTTCCCCAGACCCAGCTCCGGAGCCCACAGGCGTGGCCGATGCAGA
	AACCTCAGGAAGGTGTGTTGTGAATGTGGGAGGGAGGGTGTGGCGGTCGTGGGCTGTG
	CGGGAGTTCTGACTAGGGGAAGTGGGCTCAGCCTGGGCGCACTGGTCATCGTGCTGGC
	CAGCGCCCTCCTGCTGCTGGTGCTGGTCCTGCTCGTGGCACTCCGGGCGCGGTTCTGG
	AAGCAGTCTCGGGGCAAGGGGCTGCTGCACGGCCCCCAGGACGACCTTCGAGACAATG
	TCCTCAACTACGATGAGCAAGGAGGCGGGGAGGAGGACCAGGACGCCTACGACATCAG
	CCAGCTGCGTCACCCGACAGCGCTGAGCCTGCCTCTGGGACCGCCGCCACTTCGCAGA
	GATGCCCCGCAGGGCCGCCTGCACCCCCAGCCACCCCGAGTGCTGCCCACCAGCCCCC
	TGGACATCGCCGACTTCATCAATGATGGCTTGGAGGCTGCAGATAGTGACCCCAGTGT
	GCCGCCTTACGACACAGCCCTCATCTATGACTACGAGGGTGACGGCTCGGTGGCGGGG
	ACGCTGAGCTCCATCCTGTCCAGCCAGGGCGATGAGGACCAGGACTACGACTACCTCA
	GAGACTGGGGGCCCCGCTTCGCCCGGCTGGCAGACATGTATGGGCACCCGTGCGGGTT
	GGAGTACGGGGCCAGATGGGACCACCAGGCCAGGGAGGGTCTTTCTCCTGGGGCACTG
	CTACCCAGACACAGAGGCCGGACAGCCTGACCCTGGGGCGCAACTGGACATGCCACTC
	ccc
	ORF Start: ATG at 7		ORF Stop: TGA at 2464
	SEQ ID NO: 62	819 aa	MW at 89687.6kD
NOV23a,	MDAAFLLVLGLLAQSLCLSLGVPGWRRPTTLYPWRRAPALSRVRRAWVIPPISVSENH
CG105963-01
Protein Sequence	KRLPYPLVQVSRWKHQLASVISSIQGPGVDEEPRGVFSIAQFTGKVFLNAMLDREKTD
	RFRLRGFALDLGGSTLEDPTDLEIVVVDQNDNRPAFLQEAFTGRVLEGAVPGTYVTRA
	EATDADDPETDNAALRFSILQQGSPELFSIDELTGEIRTVQVGLDREVVAVYNLTLQV
	ADMSGDGLTATASAIITFDDINDNAPEFTRDEFFMEAIEAVSGVDVGRLEVEDRDLPG
	SPNWVARFTILEGDPDGQFTIRTDPKTNEGVLSIVKALDYESCEHYETKTHGQDKTEN
	ARAGLRAERGQAKVRVHVQDTNEPPVFQENPLRTSLAEGAPPGTLVATFSARDPDTEQ
	LQRLSYSKDYDPEDWLQVDAATGRIQTQHVLSPASPFLKGGWYRAIVLAQDASQPRTA
	TGTLSIEILEVNDHAPVLAPPPPGSLCSEPHQGPGLLLGATDEDLPPHGAPFHFQLSP
	RLPELGRNWSLSQVNPLSHHRLHPDPHLPHGPHFMSVAHQLFPRPSSGAHRRGRCRNL
	RKVCCECGREGVAVVGCAGVLTRGSGLSLGALVIVLASALLLLVLVLLVALRARFWKQ
	SRGKGLLHGPQDDLRDNVLNYDEQGGGEEDQDAYDISQLRHPTALSLPLGPPPLRRDA
	PQGRLHPQPPRVLPTSPLDIADFINDGLEAADSDPSVPPYDTALIYDYEGDGSVAGTL
	SSILSSQGDEDQDYDYLRDWGPRFARLADMYGHPCGLEYGARWDHQAREGLSPGALLP
	RHRGRTA

[0428] Further analysis of the NOV23a protein yielded the following properties shown in Table 23B.

TABLE 23B
Protein Sequence Properties NOV23a
PSort     0.6850 probability located in endoplasmic reticulum (mem-
analysis: brane); 0.6400 probability located in plasma membrane;
          0.4600 probability located in Golgi
          body; 0.1000 probability located in
          endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 22 and 23
analysis:

[0429] A search of the NOV23a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 23C.

TABLE 23C
Geneseq Results for NOV23a
		NOV23a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABG30224	Novel human diagnostic protein	1 . . . 819	750/820	(91%)	0.0
	#30215 - Homo sapiens, 814 aa.	1 . . . 814	766/820	(92%)
	[WO200175067-A2, Oct. 11, 2001]
ABG30224	Novel human diagnostic protein	1 . . . 819	750/820	(91%)	0.0
	#30215 - Homo sapiens, 814 aa.	1 . . . 814	766/820	(92%)
	[WO200175067-A2, Oct. 11, 2001]
AAB24089	Human PRO2198 protein sequence	1 . . . 819	750/820	(91%)	0.0
	SEQ ID NO:79 - Homo sapiens, 814	1 . . . 814	766/820	(92%)
	aa. [WO200053755-A2, Sep. 14, 2000
ABB57233	Mouse ischaemic condition related	35 . . . 786	313/767	(40%)	e−152
	protein sequence SEQ ID NO:606 -	149 . . . 902	436/767	(56%)
	Mus musculus, 906 aa.
	[WO200188188-A2, Nov. 22, 2001]
AAY70741	Human N-cadherin - Homo sapiens,	40 . . . 786	311/762	(40%)	e−151
	906 aa. [WO200021555-A1,	154 . . . 902	435/762	(56%)
	Apr. 20, 2000]

[0430] In a BLAST search of public sequence databases, the NOV23a protein was found to have homology to the proteins shown in the BLASTP data in Table 23D.

TABLE 23D
Public BLASTP Results for NOV23a
		NOV23a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P55291	Muscle-cadherin precursor (M-	1 . . . 819	750/820	(91%)	0.0
	cadherin) (Cadherin-15) (Cadherin-	1 . . . 814	766/820	(92%)
	14) - Homo sapiens (Human), 814
	aa.
P33146	Muscle-cadherin precursor (M-	1 . . . 787	616/791	(77%)	0.0
	cadherin) (Cadherin-15) (Cadherin-	1 . . . 783	662/791	(82%)
	14) - Mus musculus (Mouse), 784
	aa.
IJMSCM	M-cadherin - mouse, 730 aa	56 . . . 787	576/736	(78%)	0.0
	(fragment).	1 . . . 729	620/736	(83%)
Q8UVQ7	N-CADHERIN - Brachydanio rerio	39 . . . 786	316/762	(41%)	e−157
	(Zebrafish) (Zebra danjo), 893 aa.	140 . . . 889	443/762	(57%)
Q90275	NEURAL-CADHERIN	39 . . . 786	315/763	(41%)	e−154
	PRECURSOR (N-CADHERIN) -	29 . . . 779	442/763	(57%)
	Brachydanio rerio (Zebrafish)
	(Zebra danio), 783 aa.

[0431] PFam analysis predicts that the NOV23a protein contains the domains shown in the Table 23E.

TABLE 23E
Domain Analysis of NOV23a
		Identities/
	NOV23a	Similarities for	Expect
Pfam Domain	Match Region	the Matched Region	Value
cadherin	50 . . . 143	23/111	(21%)	0.011
		61/111	(55%)
cadherin	157 . . . 251	38/108	(35%)	8.7e−25
		74/108	(69%)
cadherin	265 . . . 367	34/107	(32%)	6.2e−18
		74/107	(69%)
cadherin	380 . . . 473	34/109	(31%)	7.7e−20
		71/109	(65%)
Cadherin_C_term	634 . . . 788	83/158	(53%)	5.3e−90
		146/158	(92%)

Example 24

[0432] The NOV24 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 24A.

TABLE 24A
NOV24 Sequence Analysis
	SEQ ID NO: 63	3617 bp
NOV24a,	GAGATGGGACTGCAATAGAAATCCGGGCAGCCCGAAGAGGCACCCAGCGCTCCAGCCA
CG105973-01
DNA Sequence	CCAGCTGGGCCGCCCGGGAGTCCCTGGCTCTAGACCAGCCGCGAGGAGGCGCCGCGAG
	AGAGCTGGTCCCTGCCCGCGGCCGGAGGAGGGCTAGAGCCCCTGGGCCAGCCCCCCGA
	GCCGGCTGGGCGGGCGGGCGGGTGGGAGCAGACGCCGGGCACTGTCACCACGGGTGCG
	CCGAGCGCACCGACCCGGGACACGGGCAGCTGGGGACCGCCAGATTCCACCAGCCCCC
	CTTGCCCCGCAGGGGTCCTCGGCTCGCGCTCCTGGGTAGCAGCCACCCACCGGGGCGG
	AGGGAGATGTCGCCCGGGGCCAGCCGCGGTCCCCGGGGAAGCCAGGCGCCGCTGATCG
	CGCCCCTCTGCTGCGCCGCGGCCGCGCTGGGGATGTTGCTGTGGTCCCCCGCCTGTCA
	GGCGTTCAACCTGGACGTGGAAAAGCTCACAGTGTACAGCGGCCCCAAGGGCAGCTAC
	TTCGGCTACGCCGTGGACTTCCACATACCCGACGCCCGCACAGCGAGTGTCTTGGTGG
	GGGCGCCCAAAGCCAACACCAGCCAGCCCGATATCGTGGAAGGGGGAGCCGTCTATTA
	CTGTCCTTGGCCCGCGGAGGGGTCTGCGCAGTGCAGGCAGATACCGTTTGACACCACC
	AACAACAGAAAGATCAGAGTTAATGGAACCAAAGAACCTATCGAGTTCAAATCCAATC
	AGTGGTTTGGAGCAACAGTGAAAGCTCACAAAGGAAAAGTTGTGGCCTGTGCTCCTTT
	ATATCACTGGAGAACTCTTAAACCGACACCAGAAAAGGACCCAGTTGGCACCTGCTAT
	GTAGCAATTCAGAACTTCAGCGCCTATGCCGAGTTCTCTCCTTGCCGGAACAGCAATG
	CTGATCCGGAAGGCCAGGGTTACTGCCAAGCAGGATTTAGTCTGGATTTTTATAAGAA
	TGGAGACCTTATTGTGGGAGGACCTGGGAGTTTCTACTGGCAAGGACAAGTGATCACT
	GCCAGTGTTGCAGATATCATTGCAAATTACTCATTCAAGGATATCCTCAGGAAACTGG
	CAGGAGAAAAGCAGACGGAAGTGGCTCCAGCTTCCTATGATGACAGTTACCTTGGATA
	CTCAGTTGCTGCTGGGGAGTTTACTGGGGATTCTCAGCAAGAATTGGTTGCTGGAATT
	CCAAGAGGAGCACAGAATTTTGGATATGTTTCCATCATTAACTCTACGGATATGACGT
	TTATTCAGAATTTCACGGGAGAACAGATGGCATCTTATTTTGGATATACCGTTGTCGT
	ATCAGATGTTAACAGTGATGGACTGGATGATGTCCTGGTTGGGGCACCTCTCTTTATG
	GAACGTGAATTTGAGAGCAACCCCAGAGAAGTAGGGCAAATCTACCTGTATTTGCAAG
	TGAGCTCTCTCCTCTTCAGAGACCCCCAGATCCTCACTGGCACCGAGACGTTTGGGAG
	ATTCGGTAGTGCTATGGCACACTTAGGAGACCTGAACCAAGATGGATACAATGACATT
	GCCATCGGAGTGCCTTTTGCAGGCAAGGATCAAAGAGGCAAAGTGCTCATTTATAATG
	GGAACAAAGATGGCTTAAACACCAAGCCTTCCCAAGTTCTGCAAGGAGTGTGGGCCTC
	ACATGCTGTCCCTTCCGGATTTGGCTTTACTTTAAGAGGAGATTCAGACATAGACAAG
	AATGATTACCCAGATTTGATTGTGGGTGCATTTGGAACAGGAAAAGTCGCTGTTTACA
	GAGCAAGACCGGTTGTGACTGTAGATGCCCAGCTTCTGCTGCACCCAATGATTATCAA
	TCTTGAAAATAAAACTTGCCAGGTTCCAGACTCTATGACATCTGCTGCCTGCTTTTCT
	TTAAGAGTATGTGCATCTGTCACAGGCCAGAGCATTGCAAACACAATAGTCTTGATGG
	CAGAGGTGCAATTAGATTCCCTGAAACAGAAAGGAGCTATTAAACGGACGCTCTTCCT
	TGATAACCATCAGGCTCATCGCGTCTTCCCTCTTGTGATAAAAAGGCAGAAATCCCAC
	CAGTGCCAGGATTTCATCGTTTACCTTCGAGATGAAACTGAATTCCGAGATAAATTAT
	CTCCAATCAACATTAGTTTGAATTACAGTTTGGACGAATCCACCTTTAAAGAAGGCCT
	GGAAGTGAAACCAATATTGAACTACTACAGAGAAAACATTGTTAGTGAACAGGCTCAC
	ATTCTGGTGGACTGTGGAGAAGACAATCTGTGTGTTCCTGACTTGAAGCTGTCGGCTA
	GACCAGATAAGCATCAGGTAATCATTGGAGATGAAAATCACCTTATGCTCATAATAAA
	TGCAAGAAATGAAGGGGAAGGAGCATATGAAGCTGAACTCTTTGTAATGATACCAGAA
	GAGGCAGATTATGTTGGAATCGAACGCAACAACAAGGGATTTCGACCACTGAGCTGTG
	AGTACAAGATGGAAAATGTAACCAGGATGGTGGTGTGTGACCTTGGGAACCCTATGGT
	GTCTGGAACAAATTATTCCCTGGGCCTCCGATTTGCAGTTCCACGTCTTGAGAAAACA
	AACATGAGCATTAACTTCGATCTCCAAATCAGAAGTTCCAACAAGGACAATCCAGACA
	GCAATTTTGTGAGCCTGCAAATCAACATCACTGCTGTAGCGCAGGTGGAAATAAGAGG
	AGTGTCACACCCTCCGCAGATTGTTCTGCCCATTCATAACTGGGAACCAGAAGAGGAG
	CCCCACAAAGAGGAGGAGGTTGGACCATTGGTGGAACATATTTATGAGCTGCACAATA
	TTGGACCAAGTACCATCAGTGACACCATCCTGGAGGTGGGCTGGCCTTTCTCTGCCCG
	GGATGAATTTCTTCTCTATATTTTCCATATTCAAACTCTGGGACCTCTGCAGTGCCAA
	CCAAATCCTAATATCAATCCACAGGATATAAAGCCTGCTGCCTCCCCAGAGGACACCC
	CTGAGCTCAGCGCCTTTTTGCGAAACTCTACTATTCCTCATCTTGTCAGGAAGAGGGA
	TGTACATGTGGTCGAATTCCACAGACAGAGCCCTGCAAAAATACTGAATTGTACAAAT
	ATCGAGTGTTTACAAATCTCCTGTGCAGTGGGACGACTCGAAGGAGGAGAAAGCGCAG
	TCCTGAAAGTCAGGTCACGATTATGGGCCCACACCTTCCTCCAGAGAAAAAATGATCC
	CTATGCTCTTGCATCCCTGGTGTCCTTTGAAGTTAAGAAGATGCCTTATACAGATCAG
	CCAGCAAAACTCCCAGAAGGAAGCATAGTAATTAAGACATCAGTTATTTGGGCAACTC
	CGAATGTTTCCTTCTCAATCCCATTATGGGTAATAATACTAGCAATACTTCTTGGATT
	GTTGGTTCTCGCCATTTTAACCTTAGCTTTATGGAAGTGTGGATTCTTTGACAGAGCC
	AGACCTCCTCAGGAGGACATGACCGACAGGGAACAGCTGACAAATGACAAGACCCCTG
	AGGCATGACAAGAAAAAAAAAGAAGACCAAAGACCTCAAACACTGGTCCTGTTCAAAG
	AAAAAGAAAGAACATGAGGCC
	ORF Start: ATG at 355		ORF Stop: TGA at 3544
	SEQ ID NO: 64	1063 aa	MW at 117472.3kD
NOV24a,	MSPGASRGPRGSQAPLIAPLCCAAAALGMLLWSPACQAFNLDVEKLTVYSGPKGSYFG
CG105973-01
Protein Sequence	YAVDFHIPDARTASVLVGAPKANTSQPDIVEGGAVYYCPWPAEGSAQCRQIPFDTTNN
	RKIRVNGTKEPIEFKSNQWFGATVKAHKGKVVACAPLYHWRTLKPTPEKDPVGTCYVA
	IQNFSAYAEFSPCRNSNADPEGQGYCQAGFSLDFYKNGDLIVGGPGSFYWQGQVITAS
	VADIIANYSFKDILRKLAGEKQTEVAPASYDDSYLGYSVAAGEFTGDSQQELVAGIPR
	GAQNFGYVSIINSTDMTFIQNFTGEQMASYFGYTVVVSDVNSDGLDDVLVGAPLFMER
	EFESNPREVGQIYLYLQVSSLLFRDPQILTGTETFGRFGSAMAHLGDLNQDGYNDIAI
	GVPFAGKDQRGKVLIYNGNKDGLNTKPSQVLQGVWASHAVPSGFGFTLRGDSDIDKND
	YPDLIVGAFGTGKVAVYRARPVVTVDAQLLLHPMIINLENKTCQVPDSMTSAACFSLR
	VCASVTGQSIANTIVLMAEVQLDSLKQKGAIKRTLFLDNHQAHRVFPLVIKRQKSHQC
	QDFIVYLRDETEFRDKLSPINISLNYSLDESTFKEGLEVKPILNYYRENIVSEQAHIL
	VDCGEDNLCVPDLKLSARPDKHQVIIGDENHLMLIINARNEGEGAYEAELFVMIPEEA
	DYVGIERNNKGFRPLSCEYKMENVTRMVVCDLGNPMVSGTNYSLGLRFAVPRLEKTNM
	SINFDLQIRSSNKDNPDSNFVSLQINITAVAQVEIRGVSHPPQIVLPIHNWEPEEEPH
	KEEEVGPLVEHIYELHNIGPSTISDTILEVGWPFSARDEFLLYIFHIQTLGPLQCQPN
	PNINPQDIKPAASPEDTPELSAFLRNSTIPHLVRKRDVHVVEFHRQSPAKILNCTNIE
	CLQISCAVGRLEGGESAVLKVRSRLWAHTFLQRKNDPYALASLVSFEVKKMPYTDQPA
	KLPEGSIVIKTSVIWATPNVSFSIPLWVIILAILLGLLVLAILTLALWKCGFFDRARP
	PQEDMTDREQLTNDKTPEA
	SEQ ID NO: 65	3617 bp
NOV24b,	GAGATGGGACTGCAATAGAAATCCGGGCAGCCCGAAGAGGCACCCAGCGCTCCAGCCA
CG105973-02
DNA Sequence	CCAGCTGGGCCGCCCGGGAGTCCCTGGCTCTAGACCAGCCGCGAGGAGGCGCCGCGAG
	AGAGCTGGTCCCTGCCCGCGGCCGGAGGAGGGCTAGAGCCCCTGGGCCAGCCCCCCGA
	GCCGGCTGGGCGGGCGGGCGGGTGGGAGCAGACGCCGGGCACTGTCACCACGGGTGCG
	CCGAGCGCACCGACCCGGGACACGGGCAGCTGGGGACCGCCAGATTCCACCAGCCCCC
	CTTGCCCCGCAGGGGTCCTCGGCTCGCGCTCCTGGGTAGCAGCCACCCACCGGGGCGG
	AGGGAGATGTCGCCCGGGGCCAGCCGCGGTCCCCGGGGAAGCCAGGCGCCGCTGATCG
	CGCCCCTCTGCTGCGCCGCGGCCGCGCTGGGGATGTTGCTGTGGTCCCCCGCCTGTCA
	GGCGTTCAACCTGGACGTGGAAAAGCTCACAGTGTACAGCGGCCCCAAGGGCAGCTAC
	TTCGGCTACGCCGTGGACTTCCACATACCCGACGCCCGCACAGCGAGTGTCTTGGTGG
	GGGCGCCCAAAGCCAACACCAGCCAGCCCGATATCGTGGAAGGGGGAGCCGTCTATTA
	CTGTCCTTGGCCCGCGGAGGGGTCCGCGCAGTGCAGGCAGATACCGTTTGACACCACC
	AACAACAGAAAGATCAGAGTTAATGGAACCAAAGAACCTATCGAGTTCAAATCCAATC
	AGTGGTTTGGAGCAACAGTGAAAGCTCACAAAGGAAAAGTTGTGGCCTGTGCTCCTTT
	ATATCACTGGAGAACTCTTAAACCGACACCAGAAAAGGACCCAGTTGGCACCTGCTAT
	GTAGCAATTCAGAACTTCAGCGCCTATGCCGAGTTCTCTCCTTGCCGGAACAGCAATG
	CTGATCCGGAAGGCCAGGGTTACTGCCAAGCAGGATTTAGTCTGGATTTTTATAAGAA
	TGGAGACCTTATTGTGGGAGGACCTGGGAGTTTCTACTGGCAAGGACAAGTGATCACT
	GCCAGTGTTGCAGATATCATTGCAAATTACTCATTCAAGGATATCCTCAGGAAACTGG
	CAGGAGAAAAGCAGACGGAAGTGGCTCCAGCTTCCTATGATGACAGTTACCTTGGATA
	CTCAGTTGCTGCTGGGGAGTTTACTGGGGATTCTCAGCAAGAATTGGTTGCTGGAATT
	CCAAGAGGAGCACAGAATTTTGGATATGTTTCCATCATTAACTCTACGGATATGACGT
	TTATTCAGAATTTCACGGGAGAACAGATGGCATCTTATTTTGGATATACCGTTGTCGT
	ATCAGATGTTAACAGTGATGGACTGGATGATGTCCTGGTTGGGGCACCTCTCTTTATG
	GAACGTGAATTTGAGAGCAACCCCAGAGAAGTAGGGCAAATCTACCTGTATTTGCAAG
	TGAGCTCTCTCCTCTTCAGAGACCCCCAGATCCTCACTGGCACCGAGACGTTTGGGAG
	ATTCGGTAGTGCTATGGCACACTTAGGAGACCTGAACCAAGATGGATACAATGACATT
	GCCATCGGAGTGCCTTTTGCAGGCAAGGATCAAAGAGGCAAAGTGCTCATTTATAATG
	GGAACAAAGATGGCTTAAACACCAAGCCTTCCCAAGTTCTGCAAGGAGTGTGGGCCTC
	ACATGCTGTCCCTTCCGGATTTGGCTTTACTTTAAGAGGAGATTCAGACATAGACAAG
	AATGATTACCCAGATTTGATTGTGGGTGCATTTGGAACAGGAAAAGTCGCTGTTTACA
	GAGCAAGACCGGTTGTGACTGTAGATGCCCAGCTTCTGCTGCACCCAATGATTATCAA
	TCTTGAAAATAAAACTTGCCAGGTTCCAGACTCTATGACATCTGCTGCCTGCTTTTCT
	TTAAGAGTATGTGCATCTGTCACAGGCCAGAGCATTGCAAACACAATAGTCTTGATGG
	CAGAGGTGCAATTAGATTCCCTGAAACAGAAAGGAGCTATTAAACGGACGCTCTTCCT
	TGATAACCATCAGGCTCATCGCGTCTTCCCTCTTGTGATAAAAAGGCAGAAATCCCAC
	CAGTGCCAGGATTTCATCGTTTACCTTCGAGATGAAACTGAATTCCGAGATAAATTAT
	CTCCAATCAACATTAGTTTGAATTACAGTTTGGACGAATCCACCTTTAAAGAAGGCCT
	GGAAGTGAAACCAATATTGAACTACTACAGAGAAAACATTGTTAGTGAACAGGCTCAC
	ATTCTGGTGGACTGTGGAGAAGACAATCTGTGTGTTCCTGACTTGAAGCTGTCGGCTA
	GACCAGATAAGCATCAGGTAATCATTGGAGATGAAAATCACCTTATGCTCATAATAAA
	TGCAAGAAATGAAGGGGAGGGAGCATATGAAGCTGAACTCTTTGTAATGATACCAGAA
	GAGGCAGATTATGTTGGAATCGAACGCAACAACAAGGGATTTCGACCACTGAGCTGTG
	AGTACAAGATGGAAAATGTAACCAGGATGGTGGTGTGTGACCTTGGGAACCCTATGGT
	GTCTGGAACAAATTATTCCCTGGGCCTCCGATTTGCAGTTCCACGTCTTGAGAAAACA
	AACATGAGCATTAACTTCGATCTCCAAATCAGAAGTTCCAACAAGGACAATCCAGACA
	GCAATTTTGTGAGCCTGCAAATCAACATCACTGCTGTAGCGCAGGTGGAAATAAGAGG
	AGTGTCACACCCTCCGCAGATTGTTCTGCCCATTCATAACTGGGAACCAGAAGAGGAG
	CCCCACAAAGAGGAGGAGGTTGGACCATTGGTGGAACATATTTATGAGCTGCACAATA
	TTGGACCAAGTACCATCAGTGACACCATCCTGGAGGTGGGCTGGCCTTTCTCTGCCCG
	GGATGAATTTCTTCTCTATATTTTCCATATTCAAACTCTGGGACCTCTGCAGTGCCAA
	CCAAATCCTAATATCAATCCACAGGATATAAAGCCTGCTGCCTCCCCAGAGGACACCC
	CTGAGCTCAGCGCCTTTTTGCGAAACTCTACTATTCCTCATCTTGTCAGGAAGAGGGA
	TGTACATGTGGTCGAATTCCACAGACAGAGCCCTGCAAAAATACTGAATTGTACAAAT
	ATCGAGTGTTTACAAATCTCCTGTGCAGTGGGACGACTCGAAGGAGGAGAAAGCGCAG
	TCCTGAAAGTCAGGTCACGATTATGGGCCCACACCTTCCTCCAGAGAAAAAATGATCC
	CTATGCTCTTGCATCCCTGGTGTCCTTTGAAGTTAAGAAGATGCCTTATACAGATCAG
	CCAGCAAAACTCCCAGAAGGAAGCATAGCAATTAAGACATCAGTTATTTGGGCAACTC
	CGAATGTTTCCTTCTCAATCCCATTATGGGTAATAATACTAGCAATACTTCTTGGATT
	GTTGGTTCTCGCCATTTTAACCTTAGCTTTATGGAAGTGTGGATTCTTTGACAGAGCC
	AGACCTCCTCAGGAGGACATGACCGACAGGGAACAGCTGACAAATGACAAGACCCCTG
	AGGCATGACAAGAAAAAAAAAGAAGACCAAAGACCTCAAACACTGGTCCTGTTCAAAG
	AAAAAGAAAGAACATGAGGCC
	ORF Start: ATG at 355		ORF Stop: TGA at 3544
	SEQ ID NO: 66	1063 aa	MW at 117444.2kD
NOV24b,	MSPGASRGPRGSQAPLIAPLCCAAAALGMLLWSPACQAFNLDVEKLTVYSGPKGSYFG
CG105973-02
Protein Sequence	YAVDFHIPDARTASVLVGAPKANTSQPDIVEGGAVYYCPWPAEGSAQCRQIPFDTTNN
	RKIRVNGTKEPIEFKSNQWFGATVKAHKGKVVACAPLYHWRTLKPTPEKDPVGTCYVA
	IQNFSAYAEFSPCRNSNADPEGQGYCQAGFSLDFYKNGDLIVGGPGSFYWQGQVITAS
	VADIIANYSFKDILRKLAGEKQTEVAPASYDDSYLGYSVAAGEFTGDSQQELVAGIPR
	GAQNFGYVSIINSTDMTFIQNFTGEQMASYFGYTVVVSDVNSDGLDDVLVGAPLFMER
	EFESNPREVGQIYLYLQVSSLLFRDPQILTGTETFGRFGSAMAHLGDLNQDGYNDIAI
	GVPFAGKDQRGKVLIYNGNKDGLNTKPSQVLQGVWASHAVPSGFGFTLRGDSDIDKND
	YPDLIVGAFGTGKVAVYRARPVVTVDAQLLLHPMIINLENKTCQVPDSMTSAACFSLR
	VCASVTGQSIANTIVLMAEVQLDSLKQKGAIKRTLFLDNHQAHRVFPLVIKRQKSHQC
	QDFIVYLRDETEFRDKLSPINISLNYSLDESTFKEGLEVKPILNYYRENIVSEQAHIL
	VDCGEDNLCVPDLKLSARPDKHQVIIGDENHLMLIINARNEGEGAYEAELFVMIPEEA
	DYVGIERNNKGFRPLSCEYKMENVTRMVVCDLGNPMVSGTNYSLGLRFAVPRLEKTNM
	SINFDLQIRSSNKDNPDSNFVSLQINITAVAQVEIRGVSHPPQIVLPIHNWEPEEEPH
	KEEEVGPLVEHIYELHNIGPSTISDTILEVGWPFSARDEFLLYIFHIQTLGPLQCQPN
	PNINPQDIKPAASPEDTPELSAFLRNSTIPHLVRKRDVHVVEFHRQSPAKILNCTNIE
	CLQISCAVGRLEGGESAVLKVRSRLWAHTFLQRKNDPYALASLVSFEVKKMPYTDQPA
	KLPEGSIAIKTSVIWATPNVSFSIPLWVIILAILLGLLVLAILTLALWKCGFFDRARP
	PQEDMTDREQLTNDKTPEA

[0433] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 24B.

TABLE 24B
Comparison of NOV24a against NOV24b.
		Identities/
	NOV24a Residues/	Similarities for
Protein Sequence	Match Residues	the Matched Region
NOV24b	1 . . . 1063	1010/1063 (95%)
	1 . . . 1063	1010/1063 (95%)

[0434] Further analysis of the NOV24a protein yielded the following properties shown in Table 24C.

TABLE 24C
Protein Sequence Properties NOV24a
PSort     0.4600 probability located in plasma membrane; 0.1125
analysis: probability located in microbody (peroxisome); 0.1000
          probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in endoplasmic
          reticulum (lumen)
SignalP   Cleavage site between residues 39 and 40
analysis:

[0435] A search of the NOV24a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 24D.

TABLE 24D
Geneseq Results for NOV24a
		NOV24a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM39241	Human polypeptide SEQ ID NO	29 . . . 1063	1031/1035	(99%)	0.0
	2386 - Homo sapiens, 1035 aa.	1 . . . 1035	1031/1035	(99%)
	[WO200153312-A1, Jul. 26, 2001]
AAM41027	Human polypeptide SEQ ID NO	24 . . . 1063	1024/1046	(97%)	0.0
	5958 - Homo sapiens, 1044 aa.	1 . . . 1044	1027/1046	(97%)
	[WO200153312-A1, Jul. 26, 2001]
ABG18895	Novel human diagnostic protein	8 . . . 1055	500/1052	(47%)	0.0
	#18886 - Homo sapiens, 1061 aa.	25 . . . 1049	692/1052	(65%)
	[WO200175067-A2, Oct. 11, 2001]
ABG18895	Novel human diagnostic protein	8 . . . 1055	500/1052	(47%)	0.0
	#18886 - Homo sapiens, 1061 aa.	25 . . . 1049	692/1052	(65%)
	[WO200175067-A2, Oct. 11, 2001]
AAB70508	Tissue remodeling protein alpha 5	34 . . . 1063	474/1036	(45%)	0.0
	beta 1 integrin (VLA-5) protein -	37 . . . 1049	667/1036	(63%)
	Mammalian, 1049 aa.
	[WO200111086-A2, Feb. 15, 2001]

[0436] In a BLAST search of public sequence databases, the NOV24a protein was found to have homology to the proteins shown in the BLASTP data in Table 24E.

TABLE 24E
Public BLASTP Results for NOV24a
		NOV24a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P53708	Integrin alpha-8 - Homo sapiens	39 . . . 1063	1020/1025	(99%)	0.0
	(Human), 1025 aa.	1 . . . 1025	1020/1025	(99%)
O70304	INTEGRIN ALPHA8 - Mus	46 . . . 1057	910/1012	(89%)	0.0
	musculus (Mouse), 1012 aa	1 . . . 1012	972/1012	(95%)
	(fragment).
P26009	Integrin alpha-8 precursor - Gallus	27 . . . 1063	797/1037	(76%)	0.0
	gallus (Chicken), 1044 aa.	13 . . . 1044	907/1037	(86%)
P26008	Integrin alpha-V precursor	35 . . . 1055	493/1024	(48%)	0.0
	(Vitronectin receptor alpha	16 . . . 1022	678/1024	(66%)
	subunit) (CD51) - Gallus gallus
	(Chicken), 1034 aa.
Q9MZD6	INTEGRIN ALPHA V SUBUNIT	8 . . . 1055	508/1057	(48%)	0.0
	PRECURSOR - Bos taurus	12 . . . 1035	692/1057	(65%)
	(Bovine), 1047 aa.

[0437] PFam analysis predicts that the NOV24a protein contains the domains shown in the Table 24F.

TABLE 24F
Domain Analysis of NOV24a
		Identities/
	NOV24a	Similarities for	Expect
Pfam Domain	Match Region	the Matched Region	Value
FG-GAP	54 . . . 117	22/67	(33%)	1.4e−15
		53/67	(79%)
FG-GAP	264 . . . 317	19/63	(30%)	2.1e−06
		42/63	(67%)
FG-GAP	318 . . . 383	23/66	(35%)	1.7e−15
		49/66	(74%)
FG-GAP	384 . . . 443	29/67	(43%)	2e−16
		53/67	(79%)
FG-GAP	447 . . . 501	22/66	(33%)	7.8e−10
		41/66	(62%)
integrin_A	1035 . . . 1049	10/15	(67%)	0.00011
		14/15	(93%)

Example 25

[0438] The NOV25 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 25A.

TABLE 25A
NOV25 Sequence Analysis
	SEQ ID NO: 67	1524 bp
NOV25a,	TTTGCCATCATGTTGCGGTTGGTGGCAGCTTGCCCTGAGTCATGTGTGGTGTGCACCA
CG106915-01
DNA Sequence	AAGATGTAACCCTCTGTCACCAGCTAACCTATATAGTAGCAGCCCCTATGACCACGAG
	GGTTTTAATCATCACCGATGGATATCTCTCCTCTATTGAGAGCACAAACCTGTCTCTC
	TTGTTTAATCTTGCCCTGCTCTCCCTAAGCAGAAATGGTATCGAGGATGTTCAGGAAG
	ATGCCCTGCATGGGCTTACGATGTTGCGGACCTTGTTGCTGGAGCACAACCAAATATC
	CAGCTCTTCGCTCACTGATCACACCTTCAGCAAGCTTCACAGCCTGCAGGTACTGGTG
	CTGAGCAATAATGCTCTCCGCACCCTACGAGGGTCTTGGTTCCGAAACACAAGCGGCC
	TGACCCGGCTCCAGCTGGATGGGAATCAGATTACTAATCTCACAGACAGTTCTTTCGG
	AGGCACGAATCTCCACAGTCTCAGGTATCTGGATTTATCCAACAATTTTATTTCCTAC
	ATTGGGAAAGATGCCTTCCGGCCCCTGCCTCAACTACAGGAAGTGGACCTTTCCCGAA
	ATAGGTTAGCCCACATGCCGGATGTGTTTACTCCACTGAAGCAGTTAATCCTTCTGAG
	CTTAGATAAGAACCAGTGGAGCTGCACTTGTGATCTCCATCCCCTTGCTCGGTTTTTA
	AGAAACTACATTAAGTCTTCTGCTCACACGCTCAGGAATGCCAAGGACCTAAATTGCC
	AGCCATCTACCGCAGCTGTGGCAGCTGCACAGAGTGTGCTGAGGCTGTCTGAGACCAA
	CTGTGATTCCAAAGCTCCCAACTTCACTCTGGTTCTAAAGGACAGAAGTCCCCTCCTC
	CCAGGACCAGATGTGGCCCTGCTGACTGTCCTTGGCTTCGCAGGTGCTGTTGGTCTCA
	CTTGCCTAGGTTTAGTTGTATTTAACTGGAAACTCCACCAAGGCAAAGCAAATGAACA
	CACATCAGAAAACCTTTGTTGCAGAACCTTCGATGAACCCCTGTGTGCTCATGAGGCA
	AGAAATTACCACACTAAGGGATACTGCAACTGCCACTTAACTCAGGAAAACGAGATAA
	AGGTCATGTCCATTGTGGGGTCCAGAAAAGAAATGCCACTTTTACAGGAAAATAGCCA
	TCAAGCAACATCGGCCTCTGAGTCTGCAACCCTTGACAGATCATTTAGAAACCTGAAA
	AAGAAAGACCGTGGGGTAGGCAGCACTTTATTTTGCCAGGATGGTAGATTGCTGCATT
	CGGAATGTTCAGAGCCTCCTGGAAATATGAGAGCTTTTAATGAAGCAGGCTTACTTAC
	AACATATAATCCAAGGAAAGTTCAAAAGCTATGGAATCTTGAGCCTGGAGAAGTCCAG
	CCTCAAACTCTGCAACACCATATAATAAGAACAGAAGATATCAGCAGTGACATATTTA
	GAAGAAGATATGCAACACCCGCTTCAGCCTTGGCAGGAGAAAGTCTTGAGAAGCGTTT
	AACAAATGAATCATGA
	ORF Start: ATG at 10		ORF Stop: TGA at 1522
	SEQ ID NO: 68	504 aa	MW at 56079.2kD
NOV25a,	MLRLVAACPESCVVCTKDVTLCHQLTYIVAAPMTTRVLIITDGYLSSIESTNLSLLFN
G106915-01
Protein Sequence	LALLSLSRNGIEDVQEDALHGLTMLRTLLLEHNQISSSSLTDHTFSKLHSLQVLVLSN
	NALRTLRGSWFRNTSGLTRLQLDGNQITNLTDSSFGGTNLHSLRYLDLSNNFISYIGK
	DAFRPLPQLQEVDLSRNRLAHMPDVFTPLKQLILLSLDKNQWSCTCDLHPLARFLRNY
	IKSSAHTLRNAKDLNCQPSTAAVAAAQSVLRLSETNCDSKAPNFTLVLKDRSPLLPGP
	DVALLTVLGFAGAVGLTCLGLVVFNWKLHQGKANEHTSENLCCRTFDEPLCAHEARNY
	HTKGYCNCHLTQENEIKVMSIVGSRKEMPLLQENSHQATSASESATLDRSFRNLKKKD
	RGVGSTLFCQDGRLLHSECSEPPGNMRAFNEAGLLTTYNPRKVQKLWNLEPGEVQPQT
	LQHHIIRTEDISSDIFRRRYATPASALAGESLEKRLTNES

[0439] Further analysis of the NOV25a protein yielded the following properties shown in Table 25B.

TABLE 25B
Protein Sequence Properties NOV25a
analysis: probability located in plasma membrane; 0.3000
          probability located in microbody (peroxisome);
          0.2622 probability located in mitochondrial matrix
          space
SignalP   No Known Signal Sequence Predicted
analysis:

[0440] A search of the NOV25a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 25C.

TABLE 25C
Geneseq Results for NOV25a
		NOV25a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU83655	Human PRO protein, Seq ID No:	3 . . . 237	79/264 (29%)	5e−19
	128 - Homo sapiens, 473 aa.	22 . . . 283	121/264 (44%)
	[WO200208288-A2, 31-JAN-2002]
AAB49891	Human PRO526 protein sequence -	3 . . . 237	79/264 (29%)	5e−19
	Homo sapiens, 473 aa.	22 . . . 283	121/264 (44%)
	[WO200070050-A1, 23-NOV-2000]
AAB50908	Human PRO526 protein - Homo	3 . . . 237	79/264 (29%)	5e−19
	sapiens, 473 aa. [WO200073452-	22 . . . 283	121/264 (44%)
	A2, 07-DEC-2000]
AAU04589	Human Nogo receptor - Homo	3 . . . 237	79/264 (29%)	5e−19
	sapiens, 473 aa. [WO200151520-	22 . . . 283	121/264 (44%)
	A2, 19-JUL-2001]
AAU12362	Human PRO526 polypeptide	3 . . . 237	79/264 (29%)	5e−19
	sequence - Homo sapiens, 473 aa.	22 . . . 283	121/264 (44%)
	[WO200140466-A2, 07-JUN-2001]

[0441] In a BLAST search of public sequence databases, the NOV25a protein was found to have homology to the proteins shown in the BLASTP data in Table 25D.

TABLE 25D
Public BLASTP Results for NOV25a
		NOV25a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9BGY6	HYPOTHETICAL 56.5 KDA	1 . . . 504	478/504 (94%)	0.0
	PROTEIN - Macaca fascicularis	1 . . . 504	481/504 (94%)
	(Crab eating macaque)
	(Cynomolgus monkey), 510 aa.
Q961X3	GH01279P - Drosophila	45 . . . 233	68/212 (32%)	3e−21
	melanogaster (Fruit fly), 615 aa.	313 . . . 522	103/212 (48%)
Q9N0E3	UNNAMED PROTEIN PRODUCT -	3 . . . 237	82/264 (31%)	1e−19
	Macaca fascicularis (Crab eating	22 . . . 283	125/264 (47%)
	macaque) (Cynomolgus monkey),
	473 aa.
Q9VZ84	CG7509 PROTEIN - Drosophila	45 . . . 233	69/230 (30%)	6e−19
	melanogaster (Fruit fly), 633 aa.	313 . . . 540	103/230 (44%)
Q9BZR6	NOGO RECEPTOR - Homo	3 . . . 237	79/264 (29%)	1e−18
	sapiens (Human), 473 aa.	22 . . . 283	121/264 (44%)

[0442] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25E.

TABLE 25E
Domain Analysis of NOV25a
	NOV25a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
LRR	58 . . . 81	7/25 (28%)	0.3
		19/25 (76%)
LRR	108 . . . 131	10/25 (40%)	0.11
		19/25 (76%)
LRR	132 . . . 155	8/25 (32%)	0.7
		18/25 (72%)
LRR	158 . . . 181	11/25 (44%)	0.00021
		19/25 (76%)
LRR	182 . . . 204	10/25 (40%)	0.093
		18/25 (72%)
LRRCT	214 . . . 270	15/63 (24%)	0.046
		42/63 (67%)

Example 26

[0443] The NOV26 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 26A.

TABLE 26A
NOV26 Sequence Analysis
	SEQ ID NO: 69	3757 bp
NOV26a,	CTCTTTGCCATCATGTTGCGGTTGGTGGCAGCTTGCCCTGAGTCATGTGTGGTGTGCA
CG106924-01
DNA Sequence	CCAAAGATGTAACCCTCTGTCACCAGCTAACCTATATAGTAGCAGCCCCTATGACCAC
	GAGGGTTTTAATCATCACCGATGGATATCTCTCCTCTATTGAGAGCACAAACCTGTCT
	CTCTTGTTTAATCTTGCCCTGCTCTCCCTAAGCAGAAATGGTATCGAGGATGTTCAGG
	AAGATGCCCTGCATGGGCTTACGATGTTGCGGACCTTGTTGCTGGAGCACAACCAAAT
	ATCCAGCTCTTCGCTCACTGATCACACCTTCAGCAAGCTTCACAGCCTGCAGGTACTG
	GTGCTGAGCAATAATGCTCTCCGCACCCTACGAGGGTCTTGGTTCCGAAACACAAGCG
	GCCTGACCCGGCTCCAGCTGGATGGGAATCAGATTACTAATCTCACAGACAGTTCTTT
	CGGAGGCACGAATCTCCACAGTCTCAGGTATCTGGATTTATCCAACAATTTTATTTCC
	TACATTGGGAAAGATGCCTTCCGGCCCCTGCCTCAACTACAGGAAGTGGACCTTTCCC
	GAAATAGGTTAGCCCACATGCCGGATGTGTTTACTCCACTGAAGCAGTTAATCCTTCT
	GAGCTTAGATAAGAACCAGTGGAGCTGCACTTGTGATCTCCATCCCCTTGCTCGGTTT
	TTAAGAAACTACATTAAGTCTTCTGCTCACACGCTCAGGAATGCCAAGGACCTAAATT
	GCCAGCCATCTACCGCAGCTGTGGCAGCTGCACAGAGTGTGCTGAGGCTGTCTGAGAC
	CAACTGTGATTCCAAAGCTCCCAACTTCACTCTGGTTCTAAAGGACAGAAGTCCCCTC
	CTCCCAGGACCAGATGTGGCCCTGCTGACTGTCCTTGGCTTCGCAGGTGCTGTTGGTC
	TCACTTGCCTAGGTTTAGTTGTATTTAACTGGAAACTCCACCAAGGCAAAGCAAATGA
	ACACACATCAGAAAACCTTTGTTGCAGAACCTTCGATGAACCCCTGTGTGCTCATGAG
	GCAAGAAATTACCACACTAAGGGATACTGCAACTGCCACTTAACTCAGGAAAACGAGA
	TAAAGGTCATGTCCATTGTGGGGTCCAGAAAAGAAATGCCACTTTTACAGGAAAATAG
	CCATCAAGCAACATCGGCCTCTGAGTCTGCAACCCTTGACAGATCATTTAGAAACCTG
	AAAAAGAAAGACCGTGGGGTAGGCAGCACTTTATTTTGCCAGGATGGTAGATTGCTGC
	ATTCGGAATGTTCAGAGCCTCCTGGAAATATGAGAGCTTTTAATGAAGCAGGCTTACT
	TACAACATATAATCCAAGGAAAGTTCAAAAGCTATGGAATCTTGAGCCTGGAGAAGTC
	CAGCCTCAAACTCTGCAACACCATATAATAAGAACAGAAGATATCAGCAGTGACATAT
	TTAGAAGAAGATATGCAACACCCGCTTCAGCCTTGGCAGGAGAAAGTCTTGAGAAGCG
	TTTAACAAATGAATCATGGCAGCCTCCAATAGAAAAAGAAGACAATGGCTTACACCCT
	CACAGGCAAAGACATTTTATTACAAGCTCATCATCCAAGCCTTGTGAGCCTGAGGAAC
	ACTATGTACAAAATATCGTACAAAAAAATAGATCAAAATATGATGATCCTTGTGGACT
	GTTAAAACAGAGCAAACCTAGGTATTTTCAGCCAAACAATTCTCTTATCTGTAAATAT
	GTGCCCTGTGAGCAATTTGAAGATTACATGAAAGAAAAGAAGCCAAATCGTAGACAAC
	ACTCAAAGCCTGAGAAAGAGCAAATCCAAATTAACAGTGCAATAGAAAAATTTCTTAT
	GAGTGAGGACAACATAGATTTATCAGGATTATCAACAAAAACCAAGAAAGCATATTCC
	CCAAAGAGGGTTATCTTCCATGATCCTGATTTAGTAGAAATAAATAGGTCGATGATGT
	CACCCAAAATATCAACCCCTTGGAAACGACAGAAAAATCAAAGTAACCAACTGACTAA
	GTTGGATGTTAAAAAATTTAGCAACACTGGGGAGAGAAACAAAGGAGAAAAATGGTTT
	ACTAATTCATGGGTTCTGAAAAGGAAGAGAACCCCTCAGTCTGACCTCAAAGGGAAAA
	TTAAAGGACAAAACTTAAAATTAAATTTACATCCTTTTAGAAAAGTCAGAGTCCATCC
	AGAAAAATCCTTGTCAAGTCTCCCAAAGCAATGCAAGCAGGTATTGTTGCCTCCTAAG
	AAATTATCCAAAACTTCTGAGACAGAAGCCAAAATAAATACTGTGTGTTCTGCAGATT
	TTCTTCAACAGTCAGAGAGTAGCAACTATGTTAGACTCACTTCAAAGAGGCTGCCTCT
	GAAACATGACTCAAAGCAGACCCCATATTATCAACGAAACACTAAACGTGCCCCCCTG
	CTCAGTGCTAACAACTTGCGTGTAGTCAACCAGAGCTCTATAGAAAGCAGCTGTTACT
	CAGCTGGCCACATTCCTGATGGAAACACATCAAAATTGCCCCAACCTACACCCACTGA
	TGCTGAGCACAGGCACTCACATTCTCAATTCTCAACTGAGCAAATGGAAGATGCAACT
	CAGCTTGAATCAAAAGTGCTTAGTTATTTAGCAACTACTTGGGAAAATACAGGAAGTG
	ATGTTTTACCATTCCAACATTCCAGGAGGGCTACTGACCAAGGGACAACGGAGTCCAC
	TGAGCACATGGGACAGAATGTATCAAAGACCAGTGAGTTAAATCAGTTTTCTTTGTCC
	CCGAGGAATCAAACACAACTTTTAGATGCTCACAAGACTGACAGCTACAACAAGGAAT
	ACACTTTAGACCAAAATGAAGGCTTACAACACAGAGAGCAAAATTCAAGTCATGCACA
	GCTTGAAAATAAAGAAAAAACATTAATGACAAAACCCCAAATACCACATCAAATTGTG
	GAAAATTGTATTATGGATAAGGAAGAAAATGATGTAGAAAAAAAACTTTCAAAAACAG
	AAACTTATGATTCCTCTCTCATTCCCCAAACACAATCCAAGAACAACCTATCATTTAT
	GAAGACAAATTCAATTCCATACCAAAATAGAATAGAACTTCCCAAGGATATCAGTACT
	TCTCCTGTTAGTAGTCAAGCCGTTTGGCACCTAACCAATAGTAGCGAAAAAGGAATTG
	ACAGCACAAATGCATTGCCCAGAAATGACGGCACTGAAGCACTAGAGATAAAAATAGT
	AGGGAAAGAAGAGAAAAATATGCTTGATGAAAGCAAGACAGATTCTAGTATGTTAACT
	CAGATCTCACAAATGACCTTAAAAGGCATCACAAAAGAAAGGCAGCAAACTTGGGAAA
	ATGGAACAAGTGAAAAATATATATTACATGATGCAAGCTCTGCCGAGGAGACCATTAC
	AGCTAAAGATTTAAGTATCACAAGTTCCCATGAAACCCAAAATAGAATACTTTGCAGT
	GAAGTAGATCCTGAAGTTAACAGTAATGTACATAATTTTAGAGAAGTTCAAAATATTC
	AACCAGATAAAGATAGGGCACATAAAGAAGGCGCAATGACAGTGGAGACACATGAAGC
	GCTTTCCTTCTTACCAGGGTTAAAAGACAGTTTTGAGGCAGAAAATGAGGTGTTTTTA
	GTTCCTAGCAGAATAAATGAAGCTGAAAACTCTGCTCCAAAACCTGTACTGTATCCAC
	CATCTGCTGAATATGCTACTACATCACCTTTAGAAACAGAATAAA
	ORF Start: ATG at 13		ORF Stop: TAA at 3754
	SEQ ID NO: 70	1247 aa	MW at 140902.2 kD
NOV26a,	MLRLVAACPESCVVCTKDVTLCHQLTYIVAAPMTTRVLIITDGYLSSIESTNLSLLFN
CG106924-01
Protein Sequence	LALLSLSRNGIEDVQEDALHGLTMLRTLLLEHNQISSSSLTDHTFSKLHSLQVLVLSN
	NALRTLRGSWFRNTSGLTRLQLDGNQITNLTDSSFGGTNLHSLRYLDLSNNFISYIGK
	DAFRPLPQLQEVDLSRNRLAHMPDVFTPLKQLILLSLDKNQWSCTCDLHPLARFLRNY
	IKSSAHTLRNAKDLNCQPSTAAVAAAQSVLRLSETNCDSKAPNFTLVLKDRSPLLPGP
	DVALLTVLGFAGAVGLTCLGLVVFNWKLHQGKANEHTSENLCCRTFDEPLCAHEARNY
	HTKGYCNCHLTQENEIKVMSIVGSRKEMPLLQENSHQATSASESATLDRSFRNLKKKD
	RGVGSTLFCQDGRLLHSECSEPPGNMRAFNEAGLLTTYNPRKVQKLWNLEPGEVQPQT
	LQHHIIRTEDISSDIFRRRYATPASALAGESLEKRLTNESWQPPIEKEDNGLHPHRQR
	HFITSSSSKPCEPEEHYVQNIVQKNRSKYDDPCGLLKQSKPRYFQPNNSLICKYVPCE
	QFEDYMKEKKPNRRQHSKPEKEQIQINSAIEKFLMSEDNIDLSGLSTKTKKAYSPKRV
	IFHDPDLVEINRSMMSPKISTPWKRQENQSNQLTKLDVKKFSNTGERNKGEKWFTNSW
	VLKRKRTPQSDLKGKIKGQNLKLNLHPFRKVRVHPEKSLSSLPKQCKQVLLPPKKLSK
	TSETEAKINTVCSADFLQQSESSNYVRLTSKRLPLKHDSKQTPYYQRNTKRAPLLSAN
	NLRVVNQSSIESSCYSAGHIPDGNTSKLPQPTPTDAEHRHSHSQFSTEQMEDATQLES
	KVLSYLATTWENTGSDVLPFQHSRRATDQGTTESTEHMGQNVSKTSELNQFSLSPRNQ
	TQLLDAHKTDSYNKEYTLDQNEGLQHREQNSSHAQLENKEKTLMTKPQIPHQIVENCI
	MDKEENDVEKKLSKTETYDSSLIPQTQSKNNLSFMKTNSIPYQNRIELPKDISTSPVS
	SQAVWHLTNSSEKGIDSTNALPRNDGTEALEIKIVGKEEKNMLDESKTDSSMLTQISQ
	MTLKGITKERQQTWENGTSEKYILHDASSAEETITAKDLSITSSHETQNRILCSEVDP
	EVNSNVHNFREVQNIQPDKDRAHKEGAMTVETHEALSFLPGLKDSFEAENEVFLVPSR
	INEAENSAPKPVLYPPSAEYATTSPLETE
	SEQ ID NO: 71	645 bp
NOV26b,	GGATCCGCCCTGCTCTCCCTAAGCAGAAATGGTATCGAGGATGTTCAGGAAGATGCCC
210062144 DNA
Sequence	TGCATGGGCTTACGATGTTGCGGACCTTGTTGCTGGAGCACAACCAAATATCCAGCTC
	TTCGCTCACTGATCACACCTTCAGCAAGCTTCACAGCCTGCAGGTACTGGTGCTGAGC
	AATAATGCTCTCCGCACCCTACGAGGGTCTTGGTTCCGAAACACAAGCGGCCTGACCC
	GGCTCCAGCTGGATGGGAATCAGATTACTAATCTCACAGACAGTTCTTTCGGAGGCAC
	GAATCTCCACAGTCTCAGGTATCTGGATTTATCCAACAATTTTATTTCCTACATTGGG
	AAAGATGCCTTCCGGCCCCTGCCTCAACTACAGGAAGTGGACCTTTCCCGAAATAGGT
	TAGCCCACATGCCGGATGTGTTTACTCCACTGAAGCAGTTAATCCTTCTGAGCTTAGA
	TAAGAACCAGTGGAGCTGCACTTGTGATCTCCATCCCCTTGCTCGGTTTTTAAGAAAC
	TACATTAAGTCTTCTGCTCACACGCTCAGGAATGCCAAGGACCTAAATTGCCAGCCAT
	CTACCGCAGCTGTGGCAGCTGCACAGAGTGTGCTGAGGCTGTCTGAGACCAACTGTGA
	TCTCGAG
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO: 72	215 aa	MW at 23982.8kD
NOV26b,	GSALLSLSRNGIEDVQEDALHGLTMLRTLLLEHNQISSSSLTDHTFSKLHSLQVLVLS
210062144
Protein Sequence	NNALRTLRGSWFRNTSGLTRLQLDGNQITNLTDSSFGGTNLHSLRYLDLSNNFISYIG
	KDAFRPLPQLQEVDLSRNRLAHMPDVFTPLKQLILLSLDKNQWSCTCDLHPLARFLRN
	YIKSSAHTLRNAKDLNCQPSTAAVAAAQSVLRLSETNCDLE

[0444] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 26B.

TABLE 26B
Comparison of NOV26a against NOV26b.
	NOV26a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV26b	60 . . . 270	199/211 (94%)
	3 . . . 213	199/211 (94%)

[0445] Further analysis of the NOV26a protein yielded the following properties shown in Table 26C.

TABLE 26C
Protein Sequence Properties NOV26a
PSort     0.8524 probability located in mitochondrial inner
analysis: membrane; 0.6000 probability located in endoplasmic
          reticulum (membrane); 0.3000 probability
          located in microbody (peroxisome); 0.2622
          probability located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0446] A search of the NOV26a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 26D.

TABLE 26D
Geneseq Results for NOV26a
		NOV26a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU83655	Human PRO protein, Seq ID No:	3 . . . 237	79/264 (29%)	1e−18
	128 - Homo sapiens, 473 aa.	22 . . . 283	121/264 (44%)
	[WO200208288-A2, 31-JAN-2002]
AAB49891	Human PRO526 protein sequence -	3 . . . 237	79/264 (29%)	1e−18
	Homo sapiens, 473 aa.	22 . . . 283	121/264 (44%)
	[WO200070050-A1, 23-NOV-2000]
AAB50908	Human PRO526 protein - Homo	3 . . . 237	79/264 (29%)	1e−18
	sapiens, 473 aa. [WO200073452-	22 . . . 283	121/264 (44%)
	A2, 07-DEC-2000]
AAU04589	Human Nogo receptor - Homo	3 . . . 237	79/264 (29%)	1e−18
	sapiens, 473 aa. [WO200151520-	22 . . . 283	121/264 (44%)
	A2, 19-JUL-2001]
AAU12362	Human PRO526 polypeptide	3 . . . 237	79/264 (29%)	1e−18
	sequence - Homo sapiens, 473 aa.	22 . . . 283	121/264 (44%)
	[WO200140466-A2, 07-JUN-2001]

[0447] In a BLAST search of public sequence databases, the NOV26a protein was found to have homology to the proteins shown in the BLASTP data in Table 26E.

TABLE 26E
Public BLASTP Results for NOV26a
		NOV26a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9BGY6	HYPOTHETICAL 56.5 KDA	1 . . . 504	478/504 (94%)	0.0
	PROTEIN - Macaca fascicularis	1 . . . 504	481/504 (94%)
	(Crab eating macaque)
	(Cynomolgus monkey), 510 aa.
Q961X3	GH01279P - Drosophila	45 . . . 233	68/212 (32%)	9e−21
	melanogaster (Fruit fly), 615 aa.	313 . . . 522	103/212 (48%)
Q9N0E3	UNNAMED PROTEIN PRODUCT -	3 . . . 237	82/264 (31%)	3e−19
	Macaca fascicularis (Crab eating	22 . . . 283	125/264 (47%)
	macaque) (Cynomolgus monkey),
	473 aa.
Q9VZ84	CG7509 PROTEIN - Drosophila	45 . . . 233	69/230 (30%)	1e−18
	melanogaster (Fruit fly), 633 aa.	313 . . . 540	103/230 (44%)
Q9BZR6	NOGO RECEPTOR - Homo	3 . . . 237	79/264 (29%)	3e−18
	sapiens (Human), 473 aa.	22 . . . 283	121/264 (44%)

[0448] PFam analysis predicts that the NOV26a protein contains the domains shown in the Table 26F.

TABLE 26F
Domain Analysis of NOV26a
	NOV26a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
LRR	58 . . . 81	7/25 (28%)	0.3
		19/25 (76%)
LRR	108 . . . 131	10/25 (40%)	0.11
		19/25 (76%)
LRR	132 . . . 155	8/25 (32%)	0.7
		18/25 (72%)
LRR	158 . . . 181	11/25 (44%)	0.00021
		19/25 (76%)
LRR	182 . . . 204	10/25 (40%)	0.093
		18/25 (72%)
LRRCT	214 . . . 270	15/63 (24%)	0.046
		42/63 (67%)

Example 27

[0449] The NOV27 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 27A.

TABLE 27A
NOV27 Sequence Analysis
	SEQ ID NO: 73	2358 bp
NOV27a,	GACTTCCTGGCTCGCCAGCCCCTTCCTTCCGGAGCCTGACCCGGGCCCGGGCGACCTC
CG106942-01
DNA Sequence	CCCGCGCGCTTCCCGGCCGCTGCCCAGGGGGTAGAGCGGGCGCAGCCGATCACTACCT
	GACGGCCTTTTTGGCGGCCTGGCCGGGCTGTGCAGGGTGGTAGGGCAAGACGCGCGGC
	TCCCAATTCTCCCCGGCGCCTTCGCCGGCCCCGGGCTTCTCGCGCTCCGCTCCGGGCT
	GCACCGAGTTGGGCCGGCGCGCCGCGTTGGTGTTGCCGCGCGGCGGCAGCTCAGAGTC
	TCCAGGTTGGGGCGGGCCTGGGCCGCACGGCTCCTCCACCCAGGTGACGCTGAGCAGG
	CTCAGGGTGAAGCCCAGGGAGATGCCCACGGCCACGGGCCCTGCGGGCCGCAGCACCG
	ACAGCAGCAGCGATGCCCGCATGGCGCCCGGACCGCGGGTCCCCGGCCCCGGCGAACC
	CCCAGAGCAGCCAGAGGAGTCTCCGAGGGGGCGGGACCGGGGAGGGGGCGGATCCGGA
	GGGCTCGGGCCCCGCGGGCGGGCCCGCTCCCTCCCCGCAGAGCAGAGCCAGCGGCCCG
	AGCCGAATCCCCGGAGCCGCGCCTCGATTCCCCTCCAGCAGCTGCTCTGGGCTGCGCA
	GGGTTCTTGCGCTCGGCACTGGAGCCTCAGCCGCGGCCGCAGCTGTCCGACGTGTCAC
	TGCAAGGGCCCCGCCCCCGGGGTGGGGTCTCGGGCTCTCGCTACCGGAGAGGGAGGAG
	AAGGGGGAGGTTAAAGGGGAAGGACCCCCGGAAGTGCCCCCTCCTCAGTGCGGGAGAG
	GGAGACGCCGGGGGCGGAGTCCCCTGCCTCCCGCGGCGTGGTTGGTGCGTCCCATGTG
	ACGTCAGAAGCAGCCCGCCCCTGCCTGGATGGTGCGCCCTGAGTGACGTCAGGAGCAG
	AGGCCGGAGCTGTCCATCAGCACCAAAGGCCGCGGGCGGGCTCAGGGCATGGGGCCGC
	GGTTCTGGGGCGGCCCGAGCCCCGGCTCCTGCGCCTTCCCCTTCCTCAGGCCCAGCCC
	GAGTTCCCGGACGCCGCGGGACTGGAGTGCCAGCCGGTGTTGGACGTGGAGCGGCGCC
	GCCACCGCGCCGACACCATTCTCTCCGGCCCAGCAGCCCCCTTCCTCGCACGACGGAC
	TTTCCCTGGACCCCAGCACTATGCCGGGGACTGTGGCAACACTGCGGTTCCAGCTGCT
	GCCCCCTGAGCCAGATGATGCCTTCTGGGGTGCACCTTGTGAACAGCCCCTGGAGCGC
	AGGTACCAGGCACTGCCGGCCCTCGTCTGCATCATGTGCTGTTTGTTTGGAGTCGTCT
	ACTGCTTCTTCGGTTACCGCTGCTTCAAGGCAGTGCTCTTTCTCACTGGGTTGCTGTT
	TGGCTCGGTGGTCATCTTCCTCCTCTGCTACCGAGAGCGGGTGCTAGAGACACAGCTG
	AGTGCTGGGGCGAGCGCGGGCATCGCTCTGGGCATCGGGCTGCTCTGCGGGCTGGTGG
	CCATGCTAGTGCGCAGCGTGGGCCTCTTCCTGGTGGGGCTGCTGCTCGGCCTGCTGCT
	CGCAGCTGCTGCCCTGCTGGGCTCCGCACCCTACTACCAGCCAGGCTCCGTGTGGGGT
	CCACTGGGGCTGTTGCTGGGGGGCGGCCTGCTCTGTGCCCTGCTCACTCTGCGCTGGC
	CCCGCCCACTCACCACCCTGGCCACCGCCGTGACTGGTGCTGCGCTGATCGCCACTGC
	CGCTGACTACTTCGCCGAGCTGCTACTGCTGGGGCGCTACGTGGTGGAGCGACTCCGG
	GCTGCTCCTGTGCCCCCACTCTGCTGGCGAAGCTGGGCCCTGCTGGCACTCTGGCCCC
	TGCTCAGCCTGATGGGCGTTCTGGTGCAGTGGAGGGTGACAGCTGAGGGGGACTCCCA
	CACGGAAGTGGTCATCAGCCGGCAGCGCCGACGCGTGCAACTGATGCGGATTCGGCAG
	CAGGAAGATCGCAAGGAGAAAAGGCGGAAAAAGAGACCTCCTCGGGCTCCCCTCAGAG
	GTCCCCGGGCTCCTCCCAGGCCTGGGCCACCAGATCCTGCTTATCGGCGCAGGCCAGT
	GCCCATCAAACGCTTCAATGGAGACGTCCTCTCCCCGAGCTATATCCAGAGCTTCCGA
	GACCGGCAGACCGGGAGCTCCCTGAGCTCCTTCATGGCCTCACCCACAGATGCGGACT
	ATGAGTATGGGTCCCGGGGACCTCTGACAGCCTGCTCAGGCCCCCCAGTGCGGGTATA
	GCCATATCTGTCTGTCTAGACTCTGCAGTCACCAGCTCTGACAGCTCGAGGAGGCCGG
	TAGGCTGCAATCAGCTTCCGGTTTGGTGGTCCTTCCCA
	ORF Start: ATG at 977		ORF Stop: TAG at 2261
	SEQ ID NO: 74	428 aa	MW at 46672.9 kD
NOV27a,	MGPRFWGGPSPGSCAFPFLRPSPSSRTPRDWSASRCWTWSGAATAPTPFSPAQQPPSS
CG106942-01
Protein Sequence	HDGLSLDPSTMPGTVATLRFQLLPPEPDDAFWGAPCEQPLERRYQALPALVCIMCCLF
	GVVYCFFGYRCFKAVLFLTGLLFGSVVIFLLCYRERVLETQLSAGASAGIALGIGLLC
	GLVAMLVRSVGLFLVGLLLGLLLAAAALLGSAPYYQPGSVWGPLGLLLGGGLLCALLT
	LRWPRPLTTLATAVTGAALIATAADYFAELLLLGRYVVERLRAAPVPPLCWRSWALLA
	LWPLLSLMGVLVQWRVTAEGDSHTEVVISRQRRRVQLMRIRQQEDRKEKRRKKRPPRA
	PLRGPRAPPRPGPPDPAYRRRPVPIKRFNGDVLSPSYIQSFRDRQTGSSLSSFMASPT
	DADYEYGSRGPLTACSGPPVRV

[0450] Further analysis of the NOV27a protein yielded the following properties shown in Table 27B.

TABLE 27B
Protein Sequence Properties NOV27a
PSort     0.6000 probability located in plasma membrane; 0.4000
analysis: probability located in Golgi body; 0.3000 probability located
          in endoplasmic reticulum (membrane); 0.2400 probability
          located in nucleus
SignalP   No Known Signal Sequence Predicted
analysis:

[0451] A search of the NOV27a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 27C.

TABLE 27C
Geneseq Results for NOV27a
			Identities/
		NOV27a	Similarities
		Residues/	for the
Geneseq	Protein/Organism/Length [Patent	Match	Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAM34044	Peptide #8081 encoded by probe for	79 . . . 188	60/111 (54%)	2e−25
	measuring placental gene expression -	19 . . . 124	76/111 (68%)
	Homo sapiens, 124 aa.
	[WO200157272-A2, 09-AUG-2001]
AAM20130	Peptide #6564 encoded by probe for	79 . . . 188	60/111 (54%)	2e−25
	measuring cervical gene expression -	19 . . . 124	76/111 (68%)
	Homo sapiens, 124 aa.
	[WO200157278-A2, 09-AUG-2001]
AAM73861	Human bone marrow expressed	79 . . . 188	60/111 (54%)	2e−25
	probe encoded protein SEQ ID NO:	19 . . . 124	76/111 (68%)
	34167 - Homo sapiens, 124 aa.
	[WO200157276-A2, 09-AUG-2001]
AAM61147	Human brain expressed single exon	79 . . . 188	60/111 (54%)	2e−25
	probe encoded protein SEQ ID NO:	19 . . . 124	76/111 (68%)
	33252 - Homo sapiens, 124 aa.
	[WO200157275-A2, 09-AUG-2001]
ABB24734	Protein #6733 encoded by probe for	79 . . . 188	60/111 (54%)	2e−25
	measuring heart cell gene expression -	19 . . . 124	76/111 (68%)
	Homo sapiens, 124 aa.
	[WO200157274-A2, 09-AUG-2001]

[0452] In a BLAST search of public sequence databases, the NOV27a protein was found to have homology to the proteins shown in the BLASTP data in Table 27D.

TABLE 27D
Public BLASTP Results for NOV27a
		NOV27a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9VWD2	CG14234 PROTEIN - Drosophila	103 . . . 392	82/299 (27%)	3e−20
	melanogaster (Fruit fly), 381 aa.	43 . . . 329	143/299 (47%)
Q9CRG1	2010003B14RIK PROTEIN - Mus	112 . . . 305	53/208 (25%)	6e−07
	musculus (Mouse), 556 aa	286 . . . 490	95/208 (45%)
	(fragment).
Q9NS93	SEVEN TRANSMEMBRANE	115 . . . 305	50/205 (24%)	4e−05
	PROTEIN TM7SF3 - Homo	303 . . . 504	88/205 (42%)
	sapiens (Human), 570 aa.
Q9NUS4	CDNA FLJ11169 FIS, CLONE	115 . . . 305	50/205 (24%)	4e−05
	PLACE1007282 - Homo sapiens	303 . . . 504	88/205 (42%)
	(Human), 570 aa.
O28838	Hypothetical protein AF1434 -	107 . . . 304	51/201 (25%)	7e−04
	Archaeoglobus fulgidus, 199 aa.	14 . . . 188	82/201 (40%)

Example 28

[0453] The NOV28 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 28A.

TABLE 28A
NOV28 Sequence Analysis
	SEQ ID NO: 75	2177 bp
NOV28a,	ATTCCCCTTGCCGACCCACATACACCATGAAGAGGTGCAGATCGGACGAGCTGCAGCA
CG107513-01
DNA Sequence	ACAACAGGGCGAGGAGGATGGAGCTGGGCTGGAAGATGCCGCTTCCCACCTGCCGGGC
	GCGGACCTCCGGCCTGGGGAGACCACGGGTGCTAACTCTGCTGGCGGGCCAACTTCAG
	ACGCCGGCGCTGCCGCGGCGCCCAACCCAGGTCCCCGAAGCAAGCCTCCTGATTTAAA
	GAAAATCCAGCAGCTGTCAGAGGGCTCCATGTTTGGCCACGGTCTGAAGCACCTGTTC
	CACAGCCGCCGTCGGTCTCGGGAAAGGGAGCACCAGACGTCTCAGGATTCCCAGCAGC
	ATCAGCAGCAGCAGGGTATGTCCGACCATGACTCCCCAGATGAGAAGGAGCGCTCTCC
	GGAGATGCATCGCGTCTCCTACGCCATGTCCCTGCACGACCTGCCCGCCCGGCCCACC
	GCCTTCAACCGCGTGCTGCAGCAGATCCGCTCCCGGCCCTCCATCAAGCGGGGCGCCA
	GCCTGCACAGCAGCAGTGGGGGCGGCAGCAGCGGGAGCAGCAGCCGGCGCACCAAGAG
	TAGCTCCCTGGAGCCCCAGCGTGGCAGCCCTCACCTGCTGCGCAAGGCCCCCCAGGAC
	AGCAGCCTGGCCGCCATCCTGCACCAGCACCAGTGCCGTCCCCGCTCTTCCTCCACCA
	CCGACACTGCTCTGCTGCTGGCCGACGGCAGCAACGTGTACCTCCTGGCTGAGGAGGC
	CGAAGGCATCGGGGACAAGGTGGATAAGGGAGACCTGGTGGCCCTGAGCCTCCCCGCC
	GGCCATGGTGACACCGACGGCCCCATCAGCCTGGACGTGCCCGATGGGGCACCGGACC
	CCCAGCGGACCAAGGCCGCCATTGACCACCTGCACCAGAAGATCCTGAAGATCACCGA
	GCAGATCAAGATTGAGCAGGAGGCTCGCGACGACAATGTGGCAGAGTATCTGAAACTG
	GCCAACAACGCGGACAAGCAGCAGGTGTCACGCATCAAGCAAGTGTTCGAGAAGAAGA
	ACCAGAAGTCAGCCCAGACCATCGCCCAGCTGCACAAGAAGCTGGAGCACTACCGCCG
	GCGCCTGAAGGAGATTGAGCAGAACGGGCCCTCGCGGCAGCCCAAGGACGTGCTGCGG
	GACATGCAGCAGGGGCTGAAGGACGTGGGCGCCAACGTGCGCGCAGGCATCAGCGGCT
	TTGGGGGCGGCGTGGTGGAGGGCGTCAAGGGCAGCCTCTCTGGCCTCTCACAGGCCAC
	CCACACCGCCGTGGTGTCCAAGCCCCGGGAGTTTGCCAGCCTCATCCGCAACAAGTTT
	GGCAGTGCTGACAACATCGCCCACCTGAAGGACCCCCTGGAAGATGGGCCCCCTGAGG
	AGGCAGCCCGGGCACTGAGCGGCAGTGCCACACTCGTCTCCAGCCCCAAGTATGGCAG
	CGATGATGAGTGCTCCAGCGCCACGCTCAGCTCAGCCGGGGCAGGCAGCAACTCTGGG
	GCTGGGCCTGGTGGGGCGCTGGGGAGCCCTAAGTCCAATGCACTGTATGGTGCTCCTG
	GAAACCTGGATGCTCTGCTGGAAGAGCTACGGGAGATCAAGGAGGGACAGTCTCACCT
	GGAGGACTCCATGGAAGACCTGAAGACTCAGCTGCAGAGGGACTACACCTACATGACC
	CAGTGCCTGCAGGAGGAGCGCTACAGGTACGAGCGGCTGGAGGAGCAGCTCAACGACC
	TGACTGAGCTTCATCAGAACGAGATGACGAACCTGAAGCAGGAGCTGGCCAGCATGGA
	GGAGAAGGTGGCCTACCAGTCCTATGAGAGGGCACGGGACATCCAGGAGGCCGTGGAG
	TCCTGCCTGACCCGGGTCACCAAGCTGGAGCTGCAGCAGCAACAGCAGCAGGTGGTAC
	AGCTGGAGGGCGTGGAGAATGCCAACGCGCGGGCGCTGCTGGGCAAGTTCATCAACGT
	GATCCTGGCGCTCATGGCCGTGCTGCTGGTGTTCGTGTCCACCATCGCCAACTTCATC
	ACGCCCCTCATGAAGACACGCCTGCGCATCACCAGCACCACCCTCCTGGTCCTCGTCC
	TGTTCCTCCTCTGGAAGCACTGGGACTCCCTCACCTACCTCCTGGAGCACGTGTTGCT
	GCCCAGCTGAGTGGCCAGCCACACCAACCCT
	ORF Start: ATG at 27		ORF Stop: TGA at 2154
	SEQ ID NO:76	709 aa	MW at 77503.9 kD
NOV28a,	MKRCRSDELQQQQGEEDGAGLEDAASHLPGADLRPGETTGANSAGGPTSDAGAAAAPN
CG107513-01
Protein Sequence	PGPRSKPPDLKKIQQLSEGSMFGHGLKHLFHSRRRSREREHQTSQDSQQHQQQQGMSD
	HDSPDEKERSPEMHRVSYAMSLHDLPARPTAFNRVLQQIRSRPSIKRGASLHSSSGGG
	SSGSSSRRTKSSSLEPQRGSPHLLRKAPQDSSLAAILHQHQCRPRSSSTTDTALLLAD
	GSNVYLLAEEAEGIGDKVDKGDLVALSLPAGHGDTDGPISLDVPDGAPDPQRTKAAID
	HLHQKILKITEQIKIEQEARDDNVAEYLKLANNADKQQVSRIKQVFEKKNQKSAQTIA
	QLHKKLEHYRRRLKEIEQNGPSRQPKDVLRDMQQGLKDVGANVRAGISGFGGGVVEGV
	KGSLSGLSQATHTAVVSKPREFASLIRNKFGSADNIAHLKDPLEDGPPEEAARALSGS
	ATLVSSPKYGSDDECSSATLSSAGAGSNSGAGPGGALGSPKSNALYGAPGNLDALLEE
	LREIKEGQSHLEDSMEDLKTQLQRDYTYMTQCLQEERYRYERLEEQLNDLTELHQNEM
	TNLKQELASMEEKVAYQSYERARDIQEAVESCLTRVTKLELQQQQQQVVQLEGVENAN
	SLTYLLEHVLLPS

[0454] Further analysis of the NOV28a protein yielded the following properties shown in Table 28B.

TABLE 28B
Protein Sequence Properties NOV28a
PSort     0.6000 probability located in plasma membrane; 0.4000 probability located in
analysis: Golgi body; 0.3000 probability located in endoplasmic reticulum (membrane);
          0.3000 probability located in microbody (peroxisome)
SignalP   No Known Signal Sequence Predicted
analysis:

[0455] A search of the NOV28a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 28C.

TABLE 28C
Geneseq Results for NOV28a
		NOV28a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAY94907	Human secreted protein clone	57 . . . 703	359/672 (53%)	e−178
	ca106_19x protein sequence SEQ	13 . . . 646	438/672 (64%)
	ID NO: 20 - Homo sapiens, 653 aa.
	[WO200009552-A1, 24-FEB-2000]
AAM78708	Human protein SEQ ID NO 1370 -	249 . . . 708	258/466 (55%)	e−134
	Homo sapiens, 477 aa.	26 . . . 476	326/466 (69%)
	[WO200157190-A2, 09-AUG-2001]
AAU28090	Novel human secretory protein, Seq	258 . . . 708	254/457 (55%)	e−132
	ID No 259 - Homo sapiens, 446 aa.	4 . . . 445	320/457 (69%)
	[WO200166689-A2, 13-SEP-2001]
AAM40705	Human polypeptide SEQ ID NO	352 . . . 703	224/355 (63%)	e−117
	5636 - Homo sapiens, 369 aa.	13 . . . 362	267/355 (75%)
	[WO200153312-A1, 26-JUL-2001]
AAM38919	Human polypeptide SEQ ID NO	379 . . . 703	209/328 (63%)	e−108
	2064 - Homo sapiens, 331 aa.	2 . . . 324	248/328 (74%)
	[WO200153312-A1, 26-JUL-2001]

[0456] In a BLAST search of public sequence databases, the NOV28a protein was found to have homology to the proteins shown in the BLASTP data in Table 28D.

TABLE 28D
Public BLASTP Results for NOV28a
		NOV28a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O75069	Hypothetical protein KIAA0481	69 . . . 709	638/641 (99%)	0.0
	(Cerebral protein-11) (hucep-11) -	10 . . . 650	640/641 (99%)
	Homo sapiens (Human), 650 aa
	(fragment).
Q9ULS5	Hypothetical protein KIAA1145 -	250 . . . 708	258/465 (55%)	e−134
	Homo sapiens (Human), 467 aa	17 . . . 466	325/465 (69%)
	(fragment).
AAH26867	SIMILAR TO KIAA1145	258 . . . 708	249/457 (54%)	e−129
	PROTEIN - Mus musculus	4 . . . 445	316/457 (68%)
	(Mouse), 446 aa.
O94876	Hypothetical protein KIAA0779 -	393 . . . 703	202/314 (64%)	e−105
	Homo sapiens (Human), 320 aa	1 . . . 313	241/314 (76%)
	(fragment).
Q9VI21	CG1021 PROTEIN - Drosophila	288 . . . 675	188/409 (45%)	1e−84
	melanogaster (Fruit fly), 638 aa.	252 . . . 638	248/409 (59%)

Example 29

[0457] The NOV29 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 29A.

TABLE 29A
NOV29 Sequence Analysis
	SEQ ID NO: 77	664 bp
NOV29a,	ATCGCCCCTCCTGCGCTAGCGGAGGTGATCGCCGCGGCGATGCCGGAGGAGGGTTCGG
CG107533-02
DNA Sequence	GCTGCTCGGTGCGGCGCAGGCCCTATGGGTGCGTCCTGCGGGCTGCTTTGGTCCCATT
	GGTCGCGGGCTTGGTGATCTGCCTCGTGGTGTGCATCCAGCGCTTCGCACAGGCTCAG
	CAGCAGCTGCCGCTCGAGTCACTTGGGGACCTCAGCAGGACCCCAGGCTATACTGGCA
	GGGGGGCCCAGCACTGGGCCGCTCCTTCCTGCATGGACCAGAGCTGGACAAGGGGCAG
	CTACGTATCCATCGTGATGGCATCTACATGGTACACATCCAGGTGACGCTGGCCATCT
	GCTCCTCCACGACGGCCTCCAGGCACCACCCCACCACCCTGGCCGTGGGAATCTGCTC
	TCCCGCCTCCCGTAGCATCAGCCTGCTGCGTCTCAGCTTCCACCAAGGTTGTACCATT
	GCCTCCCAGCGCCTGACGCCCCTGGCCCGAGGGGACACACTCTGCACCAACCTCACTG
	GGACACTTTTGCCTTCCCGAAACACTGATGAGACCTTCTTTGGAGTGCAGTGGGTGCG
	CCCCTGACCACTGCTGCTGATTAGGGTTTTTTAAATTTTATTTTATTTTATTTAAGTT
	CAAGAGAAAAAGTGTACACACAGGGG
	ORF Start: ATG at 40		ORF Stop: TGA at 334
	SEQ ID NO: 78	98 aa	MW at 10705.2kD
NOV29a,	MPEEGSGCSVRRRPYGCVLRAALVPLVAGLVICLVVCIQRFAQAQQQLPLESLGDLSR
CG107533-02
Protein Sequence	TPGYTGRGAQHWAAPSCMDQSWTRGSYVSIVMASTWYTSR

[0458] Further analysis of the NOV29a protein yielded the following properties shown in Table 29B.

TABLE 29B
Protein Sequence Properties NOV29a
PSort     0.7900 probability located in plasma membrane;
analysis: 0.3000 probability located in Golgi body;
          0.2000 probability located in endoplasmic
          reticulum (membrane);
          0.1000 probability located in mitochondrial inner membrane
SignalP   Cleavage site between residues 45 and 46
analysis:

[0459] A search of the NOV29a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 29C.

TABLE 29C
Geneseq Results for NOV29a
		NOV29a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAR50121	CD27L - Homo sapiens, 193 aa.	1 . . . 54	54/54 (100%)	7e−25
	[WO9405691-A, 17-MAR-1994]	1 . . . 54	54/54 (100%)
AAW41180	CD27 ligand - Homo sapiens, 216	39 . . . 54	16/16 (100%)	0.16
	aa. [US5716805-A, 10-FEB-1998]	62 . . . 77	16/16 (100%)
AAR50122	sCD27L-3 - Homo sapiens, 216 aa.	39 . . . 54	16/16 (100%)	0.16
	[WO9405691-A, 17-MAR-1994]	62 . . . 77	16/16 (100%)
AAR53971	CD27-L type II transmembrane	39 . . . 54	16/16 (100%)	0.16
	protein - Mammalia, 216 aa.	62 . . . 77	16/16 (100%)
	[WO9410308-A, 11-MAY-1994]
AAG26041	Zea mays protein fragment SEQ ID	24 . . . 72	19/55 (34%)	2.4
	NO: 30347 - Zea mays subsp. mays,	6 . . . 59	26/55 (46%)
	172 aa. [EP1033405-A2, 06-SEP-2000]

[0460] In a BLAST search of public sequence databases, the NOV29a protein was found to have homology to the proteins shown in the BLASTP data in Table 29D.

TABLE 29D
Public BLASTP Results for NOV29a
		NOV29a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96J57	TUMOR NECROSIS FACTOR	1 . . . 54	54/54 (100%)	2e−24
	(LIGAND) SUPERFAMILY,	1 . . . 54	54/54 (100%)
	MEMBER 7 - Homo sapiens
	(Human), 193 aa.
P32970	CD27 ligand (CD27-L) (CD70	1 . . . 54	54/54 (100%)	2e−24
	antigen) - Homo sapiens (Human),	1 . . . 54	54/54 (100%)
	193 aa.
Q9KFY7	HYPOTHETICAL PROTEIN	39 . . . 98	18/61 (29%)	7.4
	BH0329 - Bacillus halodurans, 423 aa.	240 . . . 300	28/61 (45%)
Q9RC64	UNKNOWN - Bacillus halodurans,	39 . . . 98	18/61 (29%)	7.4
	262 aa.	79 . . . 139	28/61 (45%)
O34255	PURL PROTEIN - Wolinella	70 . . . 93	11/24 (45%)	9.7
	succinogenes, 331 aa (fragment).	8 . . . 31	15/24 (61%)

Example 30

[0461] The NOV30 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 30A.

TABLE 30A
NOV30 Sequence Analysis
	SEQ ID NO: 79	2840 bp
NOV30a,	CGGCAGTGGCAGGAGCCGCCTTTCCGATTCCCTACGATGCGGGTGCTGAGCTATGGCA
CG107562-01
DNA Sequence	AAGGGCAGCGAAGTGACGAGCGAGACCCGCGTACGACTGTGAAAGCCACCTGGAGCCA
	CCTTGCCGGGATTGTACCTGCAGGCAGAAAGTCTTCCTACGACCGTCTTTTCCCTTAG
	AGGCACCAGAATCCCTGTAACCATTCATCCAGGTGTTGAGAAGATATGTAGCAGCCGA
	GCACCCATCTTTTGACACCGTCCTCTGAAATCAGCTTTGGAGATGCTTTCACTCTGTC
	CGTCTTCTGCAGCAGCCAGGCAGAGTGCCGACTCCTTCACAGCCGTGAGGAACTCTTC
	AGGCTCCAGAAGCTCTTAAACCTGATCTACAATGGAAAAAATTCTTTTTTATCTGTTT
	CTCATTGGCATAGCAGTGAAAGCTCAGATCTGTCCAAAGCGTTGTGTCTGTCAGATTT
	TGTCTCCTAATCTTGCAACCCTTTGTGCCAAGAAAGGGCTTTTATTTGTTCCACCAAA
	CATTGACAGAAGAACTGTGGAACTGCGGTTGGCAGACAATTTTGTTACAAATATTAAA
	AGGAAAGATTTTGCCAATATGACCAGCTTGGTGGACCTGACTCTATCCAGGAATACAA
	TAAGTTTTATTACACCTCATGCTTTCGCTGACCTACGAAATTTGAGGGCTTTGCATTT
	GAATAGCAACAGATTGACTAAAATTACAAATGATATGTTCAGTGGTCTTTCCAATCTT
	CATCATTTGATACTGAACAACAATCAGCTGACTTTAATTTCCTCTACAGCGTTTGATG
	ATGTCTTCGCCCTTGAGGAGCTGGATCTGTCCTATAATAATCTAGAAACCATTCCTTG
	GGATGCTGTTGAGAAGATGGTTAGCTTGCATACCCTTAGTTTGGATCACAATATGATT
	GATAACATTCCTAAGGGGACCTTCTCCCATTTGCACAAGATGACTCGGTTAGATGTGA
	CATCAAATAAATTGCAGAAGCTACCACCTGACCCTCTCTTTCAGCGAGCTCAGGTACT
	AGCAACCTCAGGAATCATAAGCCCATCTACTTTTGCATTAAGTTTTGGTGGAAACCCC
	TTGCATTGCAATTGTGAATTGTTGTGGTTGAGGCGTCTGTCCAGAGAAGATGACTTAG
	AGACCTGTGCTTCTCCTCCACTTTTAACTGGCCGCTACTTTTGGTCAATTCCTGAAGA
	AGAGTTTTTGTGTGAGCCTCCTCTCATTACTCGTCATACACATGAGATGAGAGTCCTG
	GAGGGACAAAGGGCAACACTGAGGTGCAAAGCCAGGGGAGACCCTGAGCCTGCAATTC
	ACTGGATTTCTCCTGAAGGGAAGCTTATTTCAAATGCAACAAGATCTCTGGTGTATGA
	TAACGGAACACTTGACATTCTTATCACAACTGTAAAGGATACAGGTGCTTTTACCTGC
	ATTGCTTCCAATCCTGCTGGGGAAGCAACACAAATAGTGGATCTTCATATAATTAAGC
	TCCCTCACTTACTAAATAGTACAAACCATATCCATGAGCCTGATCCTGGTTCTTCAGA
	TATCTCAACTTCTACCAAGTCAGGTTCTAATACAAGCAGTAGTAATGGTGATACTAAA
	TTGAGTCAAGATAAAATTGTGGTGGCAGAAGCTACATCATCAACGGCACTACTTAAAT
	TTAATTTTCAAAGAAATATCCCTGGAATACGTATGTTTCAAATCCAGTACAATGGTAC
	TTATGATGACACCCTTGTTTACAGGATGATACCTCCTACGAGCAAAACTTTTCTGGTC
	AATAATCTGGCTGCTGGAACTATGTATGACTTGTGTGTCTTGGCCATATATGATGATG
	GCATCACTTCCCTCACTGCCACAAGAGTCGTGGGTTGCATCCAGTTTACTACGGAACA
	GGATTATGTGCGTTGCCATTTCATGCAGTCCCAGTTTTTGGGAGGCACCATGATTATT
	ATTATTGGTGGAATCATTGTAGCATCTGTGCTGGTATTCATCATTATTCTGATGATCC
	GGTATAAGGTTTGCAACAATAATGGGCAACACAAGGTCACCAAGGTTAGCAATGTTTA
	TTCCCAAACTAACGGGGCTCAAATACAAGGCTGTAGTGTAACGCTGCCCCAGTCCGTG
	TCCAAACAAGCTGTGGGACACGAAGAGAATGCCCAGTGTTGTAAAGCTACCAGTGACA
	ATGTGATTCAATCTTCAGAAACTTGTTCGAGTCAAGACTCCTCTACCACTACCTCTGC
	TTTGCCTCCTTCCTGGACTTCAAGCACTTCTGTGTCCCAAAAGCAGAAAAGAAAGACT
	GGCACAAAGCCAAGTACAGAACCACAGAATGAAGCCGTCACAAATGTTGAATCCCAAA
	ACACTAACAGGAACAACTCAACTGCCTTGCAGTTAGCTAGCCGTCCTCCCGATTCTGT
	CACAGAGGGGCCCACGTCTAAAAGAGCACATATAAAGCCAAGTAAGTTTATCACTTTG
	CCTGCTGAGAGATCCGGAGCAAGGCACAAGTACTCCCTCAATGGAGAATTAAAGGAAT
	ACTATTGTTATATTAACTCGCCGAACACATGTGGACTGTTTCCTAAAAGAAGCATGTC
	TATGAATGTGATGTTTATTCAGTCTGACTGTTCTGATGGTCATAGTGGAAAGGCAACT
	CTCAAATTCTGAGGGACTACTGGAAAGCTCTGTGTAATTTATAATTTCTTTTTCATGA
	AAAATCATTTTGAGAACTCACATAGAAGATTGGAATTTGCAATTCCAATGCTGTGTAT
	AAATCAACCTTCTCAGATGCTTTGCTGACTAATGTTGACCAGATTGTCCAGGAAAC
	ORF Start: ATG at 380		ORF Stop: TGA at 2678
	SEQ ID NO: 80	766 aa	MW at 84690.6 kD
NOV30a,	MEKILFYLFLIGIAVKAQICPKRCVCQILSPNLATLCAKKGLLFVPPNIDRRTVELRL
CG107562-01
Protein Sequence	ADNFVTNIKRKDFANMTSLVDLTLSRNTISFITPHAFADLRNLRALHLNSNRLTKITN
	DMFSGLSNLHHLILNNNQLTLISSTAFDDVFALEELDLSYNNLETIPWDAVEKMVSLH
	TLSLDHNMIDNIPKGTFSHLHKMTRLDVTSNKLQKLPPDPLFQRAQVLATSGIISPST
	FALSFGGNPLHCNCELLWLRRLSREDDLETCASPPLLTGRYFWSIPEEEFLCEPPLIT
	RHTHEMRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNATRSLVYDNGTLDILITT
	VKDTGAFTCIASNPAGEATQIVDLHIIKLPHLLNSTNHIHEPDPGSSDISTSTKSGSN
	TSSSNGDTKLSQDKIVVAEATSSTALLKFNFQRNIPGIRMFQIQYNGTYDDTLVYRMI
	PPTSKTFLVNNLAAGTMYDLCVLAIYDDGITSLTATRVVGCIQFTTEQDYVRCHFMQS
	QFLGGTMIIIIGGIIVASVLVFIIILMIRYKVCNNNGQHKVTKVSNVYSQTNGAQIQG
	CSVTLPQSVSKQAVGHEENAQCCKATSDNVIQSSETCSSQDSSTTTSALPPSWTSSTS
	VSQKQKRKTGTKPSTEPQNEAVTNVESQNTNRNNSTALQLASRPPDSVTEGPTSKPAH
	IKPSKFITLPAERSGARHKYSLNGELKEYYCYINSPNTCGLFPKRSMSMNVMFIQSDC
	SDGHSGKATLKF
	SEQ ID NO: 81	2388 bp
NOV30b,	GCTCTTAAACCTGATCTACAATGGAAAAAATTCTTTTTTATCTGTTTCTCATTGGCAT
CG107562-02
DNA Sequence	AGCAGTGAAAGCTCAGATCTGTCCAAAGCGTTGTGTCTGTCAGATTTTGTCTCCTAAT
	CTTGCAACCCTTTGTGCCAAGAAAGGGCTTTTATTTGTTCCACCAAACATTGACAGAA
	GAACTGTGGAACTGCGGTTGGCAGACAATTTTGTTACAAATATTAAAAGGAAAGATTT
	TGCCAATATGACCAGCTTGGTGGACCTGACTCTATCCAGGAATACAATAAGTTTTATT
	ACACCTCATGCTTTCGCTGACCTACGAAATTTGAGGGCTTTGCATTTGAATAGCAACA
	GATTGACTAAAATTACAAATGATATGTTCAGTGGTCTTTCCAATCTTCATCATTTGAT
	ACTGAACAACAATCAGCTGACTTTAATTTCCTCTACAGCGTTTGATGATGTCTTCGCC
	CTTGAGGAGCTGGATCTGTCCTATAATAATCTAGAAACCATTCCTTGGGATGCTGTTG
	AGAAGATGGTTAGCTTGCATACCCTTAGTTTGGATCACAATATGATTGATAACATTCC
	TAAGGGGACCTTCTCCCATTTGCACAAGATGACTCGGTTAGATGTGACATCAAATAAA
	TTGCAGAAGCTACCACCTGACCCTCTCTTTCAGCGAGCTCAGGTACTAGCAACCTCAG
	GAATCATAAGCCCATCTACTTTTGCATTAAGTTTTGGTGGAAACCCCTTGCATTGCAA
	TTGTGAATTGTTGTGGTTGAGGCGTCTGTCCAGAGAAGATGACTTAGAGACCTGTGCT
	TCTCCTCCACTTTTAACTGGCCGCTACTTTTGGTCAATTCCTGAAGAAGAGTTTTTGT
	GTGAGCCTCCTCTCATTACTCGTCATACACATGAGATGAGAGTCCTGGAGGGACAAAG
	GGCAACACTGAGGTGCAAAGCCAGGGGAGACCCTGAGCCTGCAATTCACTGGATTTCT
	CCTGAAGGGAAGCTTATTTCAAATGCAACAAGATCTCTGGTGTATGATAACGGAACAC
	TTGACATTCTTATCACAACTGTAAAGGATACAGGTGCTTTTACCTGCATTGCTTCCAA
	TCCTGCTGGGGAAGCAACACAAATAGTGGATCTTCATATAATTAAGCTCCCTCACTTA
	CTAAATAGTACAAACCATATCCATGAGCCTGATCCTGGTTCTTCAGATATCTCAACTT
	CTACCAAGTCAGGTTCTAATACAAGCAGTAGTAATGGTGATACTAAATTGAGTCAAGA
	TAAAATTGTGGTGGCAGAAGCTACATCATCAACGGCACTACTTAACTTTACTTTTCAA
	AGAACTATCCCTGGAATACGTATGTTTCAAATCCAGTACAATGGTACTTATGATGACA
	CCCTTGTTTACAGGATGATACCTCCTACGAGCAAAACTTTTCTGGTCAATAATCTGGC
	TGCTGGAACTATGTATGACTTGTGTGTCTTGGCCATATATGATGATGGCATCACTTCC
	CTCACTGCCACAAGAGTCGTGGGTTGCATCCAGTTTACTACGGAACAGGATTATGTGC
	GTTGCCATTTCATGCAGTCCCAGTTTTTGGGAGGCACCATGATTATTATTATTGGTGG
	AATCATTGTAGCATCTGTGCTGGTATTCATCATTATTCTGATGATCCGGTATAAGGTT
	TGCAACAATAATGGGCAACACAAGGTCACCAAGGTTAGCAATGTTTATTCCCAAACTA
	ACGGGGCTCAAATACAAGGCTGTAGTGTAACGCTGCCCCAGTCCGTGTCCAAACAAGC
	TGTGGGACACGAAGAGATTGCCCAGTGTTGTAAAGCTACCAGTGACAATGTGATTCAA
	TCTTCAGAAACTTGTTCGAGTCAGGACTCCTCTACCACTACCTCTGCTTTGCCTCCTT
	CCTGGACTTCAAGCACTTCTGTGTCCCAAAAGCAGAAAAGAAAGACTGGCACAAAGCC
	AAGTACAGAACCACAGAATGAAGCCGTCACAAATGTTGAATCCCAAAACACTAACAGG
	AACAACTCAACTGCCTTGCAGTTAGCTAGCCGTCCTCCCGATTCTGTCACAGAGGGGC
	CCACGTCTAAAAGAGCACATATAAAGCCAAATGCTTTGCTGACTAATGTTGACCAGAT
	TGTCCAGGAAACACAGAGGCTGGAGTTAATCTGAAGAGCACCACTTCTCCTCTCTCTC
	CTGAAAAAATTTGCCACTGATATTTTTACTGGATAAAATTCAAAAATGTTTCAATTCA
	CAAAGGCTAATTGTTGAACTGGTGTCGTAGAAGAAATTGTCTACAGGAGCCAAGGTGA
	AAGTCTCTGATGACGGCGGAACTGGCTCCATTAGACCATGGTTCATCCTCTTTTAAAA
	ACAAATTTTT
	ORF Start: ATG at 21		ORF Stop: TGA at 2178
	SEQ ID NO: 82	719 aa	MW at 79402.7 kD
NOV30b,	MEKILFYLFLIGIAVKAQICPKRCVCQILSPNLATLCAKKGLLFVPPNIDRRTVELRL
CG107562-02
Protein Sequence	ADNFVTNIKRKDFANMTSLVDLTLSRNTISFITPHAFADLPNLRALHLNSNRLTKITN
	DMFSGLSNLHHLILNNNQLTLISSTAFDDVFALEELDLSYNNLETIPWDAVEKMVSLH
	TLSLDHNMIDNIPKGTFSHLHKMTRLDVTSNKLQKLPPDPLFQRAQVLATSGIISPST
	FALSFGGNPLHCNCELLWLRRLSREDDLETCASPPLLTGRYFWSIPEEEFLCEPPLIT
	RHTHEMRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNATRSLVYDNGTLDILITT
	VKDTGAFTCIASNPAGEATQIVDLHIIKLPHLLNSTNHIHEPDPGSSDISTSTKSGSN
	TSSSNGDTKLSQDKIVVAEATSSTALLNFTFQRTIPGIRMFQIQYNGTYDDTLVYRMI
	PPTSKTFLVNNLAAGTMYDLCVLAIYDDGITSLTATRVVGCIQFTTEQDYVRCHFMQS
	QFLGGTMIIIIGGIIVASVLVFIIILMIRYKVCNNNGQHKVTKVSNVYSQTNGAQIQG
	CSVTLPQSVSKQAVGHEEIAQCCKATSDNVIQSSETCSSQDSSTTTSALPPSWTSSTS
	VSQKQKRKTGTKPSTEPQNEAVTNVESQNTNRNNSTALQLASRPPDSVTEGPTSKRAH
	IKPNALLTNVDQIVQETQRLELI
	SEQ ID NO: 83	1545 bp
NOV30c,	GGATCCCAGATCTGTCCAAAGCGTTGTGTCTGTCAGATTTTGTCTCCTAATCTTGCAA
210086373
DNA Sequence	CCCTTTGTGCCAAGAAAGGGCTTTTATTTGTTCCACCAAACATTGACAGAAGAACTGT
	GGAACTGCGGTTGGCAGACAATTTTGTTACAAATATTAAAAGGAAAGATTTTGCCAAT
	ATGAGCAGCTTGGTGGACCTGACTCTATCCAGGAATACAATAAGTTTTATTACACCTC
	ATGCTTTCGCTGACCTACGAAATTTGAGGGCTTTGCATTTGAATAGCAACAGATTGAC
	TAAAATTACAAATGATATGTTCAGTGGTCTTTCCAATCTTCATCATTTGATACTGAAC
	AACAATCAGCTGACTTTAATTTCCTCTACAGCGTTTGATGATGTCTTCGCCCTTGAGG
	AGCTGGATCTGTCCTATAATAATCTAGAAACCATTCCTTGGGATGCTGTTGAGAAGAT
	GGTTAGCTTGCATACCCTTAGTTTGGATCACAATATGATTGATAACATTCCTAAGGGG
	ACCTTCTCCCATTTGCACAAGATGACTCGGTTAGATGTGACATCAAATAAATTGCAGA
	AGCTACCACCTGACCCTCTCTTTCAGCGAGCTCAGGTACTAGCAACCTCAGGAATCAT
	AAGCCCATCTACTTTTGCATTAAGTTTTGGTGGAAACCCCTTGCATTGCAATTGTGAA
	TTGTTGTGGTTGAGGCGTCTGTCCAGAGAAGATGACTTAGAGACCTGTGCTTCTCCTC
	CACTTTTAACTGGCCGCTACTTTTGGTCAATTCCTGAAGAAGAGTTTTTGTGTGAGCC
	TCCTCTCATTACTCGTCATACACATGAGATGAGAGTCCTGGAGGGACAAAGGGCAACA
	CTGAGGTGCAAAGCCAGGGGAGACCCTGAGCCTGCAATTCACTGGATTTCTCCTGAAG
	GGAAGCTTATTTCAAATGCAACAAGATCTCTGGTGTATGATAACGGAACACTTGACAT
	TCTTATCACAACTGTAAAGGATACAGGTGCTTTTACCTGCATTGCTTCCAATCCTGCT
	GGGGAAGCAACACAAATAGTGGATCTTCATATAATTAAGCTCCCTCACTTACTAAATA
	GTACAAACCATATCCATGAGCCTGATCCTGGTTCTTCAGATATCTCAACTTCTACCAA
	GTCAGGTTCTAATACAAGCAGTAGTAATGGTGATACTAAATTGAGTCAAGATAAAATT
	GTGGTGGCAGAAGCTACATCATCAACGGCACTACTTAAATTTAATTTTCGAAGAAATA
	TCCCTGGAATACGTATGTTTCAAATCCAGTACAATGGTACTTATGATGACACCCTTGT
	TTACAGAATGATACCTCCTACGAGCAAAACTTTTCTGGTCAATAATCTGGCTGCTGGA
	ACTATGTATGACTTGTGTGTCTTGGCCATATATGATGATGGCATCACTTCCCTCACTG
	CCACAAGAGTCGTGGGTTGCATCCAGTTTACTACGGAACAGGATTATGTGCGTTGCCA
	TTTCATGCAGTCCCAGTTTTTGGGAGGCACCCTCGAG
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO: 84	515 aa	MW at 57372.8kD
NOV30c,	GSQICPKRCVCQILSPNLATLCAKKGLLFVPPNIDRRTVELRLADNFVTNIKRKDFAN
210086373
Protein Sequence	MTSLVDLTLSRNTISFITPHAFADLRNLRALHLNSNRLTKITNDMFSGLSNLHHLILN
	NNQLTLISSTAFDDVFALEELDLSYNNLETIPWDAVEKMVSLHTLSLDHNMIDNIPKG
	TFSHLHKMTRLDVTSNKLQKLPPDPLFQRAQVLATSGIISPSTFALSFGGNPLHCNCE
	LLWLRRLSREDDLETCASPPLLTGRYFWSIPEEEFLCEPPLITRHTHEMRVLEGQRAT
	LRCKARGDPEPAIHWISPEGKLISNATRSLVYDNGTLDILITTVKDTGAFTCIASNPA
	GEATQIVDLHIIKLPHLLNSTNHIHEPDPGSSDISTSTKSGSNTSSSNGDTKLSQDKI
	VVAEATSSTALLKFNFRRNIPGIRMFQIQYNGTYDDTLVYRMIPPTSKTFLVNNLAAG
	TMYDLCVLAIYDDGITSLTATRVVGCIQFTTEQDYVRCHFMQSQFLGGTLE
	SEQ ID NO: 85	1545 bp
NOV30d,	GGATCCCAGATCTGTCCAAAGCGTTGTGTCTGTCAGATTTTGTCTCCTAATCTTGCAA
210086403
DNA Sequence	CCCTTTGTGCCAAGAAAGGGCTTTTATTTGTTCCACCAAACATTGACAGAAGAACTGT
	GGAACTGCGGTTGGCAGACAATTTTGTTACAAATATTAAAAGGAAAGATTTTGCCAAT
	ATGACCAGCTTGGTGGACCTGACTCTATCCAGGAATACAATAAGTTTTATTACACCTC
	ATGCTTTCGCTGACCTACGAAATTTGAGGGCTTTGCATTTGAATAGCAACAGATTGAC
	TAAAATTACAAATGATATGTTCAGTGGTCTTTCCAATCTTCATCATTTGATACTGAAC
	AACAATCAGCTGACTTTAATTTCCTCTACAGCGTTTGATGATGTCTTCACCCTTGAGG
	AGCTGGATCTGTCCTATAATAATCTAGAAACCATTCCTTGGGATGCTGTTGAGAAGAT
	GGTTAGCTTGCATACCCTTAGTTTGGATCACAATATGATTGATAACATTCCTAAGGGG
	ACCTTCTCCCATTTGCACAAGATGACTCGGTTAGATGTGACATCAAATAAATTGCAGA
	AGCTACCACCTGACCCTCTCTTTCAGCGAGCTCAGGTACTAGCAACCTCAGGAATCAT
	AAGCCCATCTACTTTTGCATTAAGTTTTGGTGGAAACCCCTTGCATTGCAATTGTGAA
	TTGTTGTGGTTGAGGCGTCTGTCCAGAGAAGATGACTTAGAGACCTGTGCTTCTCCTC
	CACTTTTAACTGGCCGCTACTTTTGGTCAATTCCTGAAGAAGAGTTTTTGTGTGAGCC
	TCCTCTCATTACTCGTCATACACATGAGATGAGAGTCCTGGAGGGACAAAGGGCAACA
	CTGAGGTGCAAAGCCAGGGGAGACCCTGAGCCTGCAATTCACTGGATTTCTCCTGAAG
	GGAAGCTTATTTCAAATGCAACAAGATCTCTGGTGTATGATAACGGAACACTTGACAT
	TCTTATCACAACTGTAAAGGATACAGGTGCTTTTACCTGCATTGCTTCCAATCCTGCT
	GGGGAAGCAACACAAATAGTGGATCTTCATATAATTAAGCTCCCTCACTTACTAAATA
	GTACAAACCATATCCATGAGCCTGATCCTGGTTCTTCAGATATCTCAACTTCTACCAA
	GTCAGGTTCTAATACAAGCAGTAGTAATGGTGATACTAAATTGAGTCAAGATAAAATT
	GTGGTGGCAGAAGCTACATCATCAACGGCACTACTTAAATTTAATTTTCAAAGAAATA
	TCCCTGGAATACGTATGTTTCAAATCCAGTACAATGGTACTTATGATGACACCCTTGT
	TTACAGAATGATACCTCCTACGAGCAAAACTTTTCTGGTCAATAATCTGGCTGCTGGA
	ACTATGTATGACTTGTGTGTCTTGGCCATATATGATGATGGCATCACTTCCCTCACTG
	CCACAAGAGTCGTGGGTTGCATCCAGTTTACTACGGAACAGGATTATGTGCGTTGCCA
	TTTCATGCAGTCCCAGTTTTTGGGAGGCACCCTCGAG
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO: 86	515 aa	MW at 57374.8kD
NOV30d,	GSQICPKRCVCQILSPNLATLCAKKGLLFVPPNIDRRTVELRLADNFVTNIKRKDFAN
210086403
Protein Sequence	MTSLVDLTLSRNTISFITPHAFADLRNLRALHLNSNRLTKITNDMFSGLSNLHHLILN
	NNQLTLISSTAFDDVFTLEELDLSYNNLETIPWDAVEKMVSLHTLSLDHNMIDNIPKG
	TFSHLHKMTRLDVTSNKLQKLPPDPLFQRAQVLATSGIISPSTFALSFGGNPLHCNCE
	LLWLRRLSREDDLETCASPPLLTGRYFWSIPEEEFLCEPPLITRHTHEMRVLEGQRAT
	LRCKARGDPEPAIHWISPEGKLISNATRSLVYDNGTLDILITTVKDTGAFTCIASNPA
	GEATQIVDLHIIKLPHLLNSTNHIHEPDPGSSDISTSTKSGSNTSSSNGDTKLSQDKI
	VVAEATSSTALLKFNFQRNIPGIRMFQIQYNGTYDDTLVYRMIPPTSKTFLVNNLAAG
	TMYDLCVLAIYDDGITSLTATRVVGCIQFTTEQDYVRCHFMQSQFLGGTLE
	SEQ ID NO: 87	1545bp
NOV30e,	GGATCCCAGATCTGTCCAAAGCGTTGTGTCTGTCAGATTTTGTCTCCTAATCTTGCAA
210086422
DNA Sequence	CCCTTTGTGCCAAGAAAGGGCTTTTATTTGTTCCACCAAACATTGACAGAAGAACTGT
	GGAACTGCGGTTGGCAGACAATTTTGTTACAAATATTAAAAGGAAAGATTTTGCCAAT
	ATGACCAGCTTGGTGGACCTGACTCTATCCAGGAATACAATAAGTTTTATTACACCTC
	ATGCTTTCGCTGACCTACGAAATTTGAGGGCTTTGCATTTGAATAGCAACAGATTGAC
	TAAAATTACAAATGATATGTTCAGTGGTCTTTCCAATCTTCATCATTTGATACTGAAC
	AACAATCAGCTGACTTTAATTTCCTCTACAGCGTTTGATGATGTCTTCACCCTTGAGG
	AGCTGGATCTGTCCTATAATAATCTAGAAACCATTCCTTGGGATGCTGTTGAGAAGAT
	GGTTAGCTTGCATACCCTTAGTTTGGATCACAATATGATTGATAACATTCCTAAGGGG
	ACCTTCTCCCATTTGCACAAGATGACTCGGTTAGATGTGACATCAAATAAATTGCAGA
	AGCTACCACCTGACCCTCTCTTTCAGCGAGCTCAGGTACTAGCAACCTCAGGAATCAT
	AAGCCCATCTACTTTTGCATTAAGTTTTGGTGGAAACCCCTTGCATTGCAATTGTGAA
	TTGTTGTGGTTGAGGCGTCTGTCCAGAGAAGATGACTTAGAGACCTGTGCTTCTCCTC
	CACTTTTAACTGGCCGCTACTTTTGGTCAATTCCTGAAGAAGAGTTTTTGTGTGAGCC
	TCCTCTCATTACTCGTCATACACATGAGATGAGAGTCCTGGAGGGACAAAGGGCAACA
	CTGAGGTGCAAAGCCAGGGGAGACCCTGAGCCTGCAATTCACTGGATTTCTCCTGAAG
	GGAAGCTTATTTCAAATGCAACAAGATCTCTGGTGTATGATAACGGAACACTTGACAT
	TCTTATCACAACTGTAAAGGATACAGGTGCTTTTACCTGCATTGCTTCCAATCCTGCT
	GGGGAAGCAACACAAATAGTGGATCTTCATATAATTAAGCTCCCTCACTTACTAAATA
	GTACAAACCATATCCATGAGCCTGATCCTGGTTCTTCAGATATCTCAACTTCTACCAA
	GTCAGGTTCTAATACAAGCAGTAGTAATGGTGATACTAAATTGAGTCAAGATAAAATT
	GTGGTGGCAGAAGCTACATCATCAACGGCACTACTTAAATTTAATTTTCAAAGAAATA
	TCCCTGGAATACGTATGTTTCAAATCCAGTACAATGGTACTTATGATGACACCCTTGT
	TCACAGAATGATACCTCCTACGAGCAAAACTTTTCTGGTCAATAATCTGGCTGCTGGA
	ACTATGTATGACTTGTGTGTCTTGGCCATATATGATGATGGCATCACTTCCCTCACTG
	CCACAAGAGTCGTGGGTTGCATCCAGTTTACTACGGAACAGGATTATGTGCGTTGCCA
	TTTCATGCAGTCCCAGTTTTTGGGAGGCACCCTCGAG
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO: 88	515 aa	MW at 57348.7 kD
NOV30e,	GSQICPKRCVCQILSPNLATLCAKKGLLFVPPNIDRRTVELRLADNFVTNIKRKDFAN
210086422
Protein Sequence	MTSLVDLTLSRNTISFITPHAFADLRNLRALHLNSNRLTKITNDMFSGLSNLHHLILN
	NNQLTLISSTAFDDVFTLEELDLSYNNLETIPWDAVEKMVSLHTLSLDHNMIDNIPKG
	TFSHLHKMTRLDVTSNKLQKLPPDPLFQRAQVLATSGIISPSTFALSFGGNPLHCNCE
	LLWLRRLSREDDLETCASPPLLTGRYFWSIPEEEFLCEPPLITRHTHEMRVLEGQRAT
	LRCKARGDPEPAIHWISPEGKLISNATRSLVYDNGTLDILITTVKDTGAFTCIASNPA
	GEATQIVDLHIIKLPHLLNSTNHIHEPDPGSSDISTSTKSGSNTSSSNGDTKLSQDKI
	VVAEATSSTALLKFNFQRNIPGIRMFQIQYNGTYDDTLVHRMIPPTSKTFLVNNLAAG
	TMYDLCVLAIYDDGITSLTATRVVGCIQFTTEQDYVRCHFMQSQFLGGTLE

[0462] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 30B.

TABLE 30B
Comparison of NOV30a against NOV30b through NOV30e.
	Protein	NOV30a Residues/	Identities/Similarities for
	Sequence	Match Residues	the Matched Region
	NOV30b	1 . . . 704	624/704 (88%)
		1 . . . 704	626/704 (88%)
	NOV30c	17 . . . 529	465/513 (90%)
		2 . . . 514	468/513 (90%)
	NOV30d	17 . . . 529	465/513 (90%)
		2 . . . 514	467/513 (90%)
	NOV30e	17 . . . 529	464/513 (90%)
		2 . . . 514	467/513 (90%)

[0463] Further analysis of the NOV30a protein yielded the following properties shown in Table 30C.

TABLE 30C
Protein Sequence Properties NOV30a
PSort     0.6850 probability located in endoplasmic
analysis: reticulum (membrane);
          0.6400 probability located in plasma membrane;
          0.4600 probability located in Golgi body;
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 18 and 19
analysis:

[0464] A search of the NOV30a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 30D.

TABLE 30D
Geneseq Results for NOV30a
		NOV30a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAG67505	Amino acid sequence of a human	1 . . . 766	765/766 (99%)	0.0
	secreted polypeptide - Homo	1 . . . 766	766/766 (99%)
	sapiens, 766 aa. [WO200166690-
	A2, 13-SEP-2001]
AAB09968	Human brain-specific	1 . . . 756	374/780 (47%)	0.0
	transmembrane glycoprotein -	1 . . . 770	505/780 (63%)
	Homo sapiens, 789 aa.
	[WO200031256-A1, 02-JUN-2000]
AAM39059	Human polypeptide SEQ ID NO	1 . . . 756	373/780 (47%)	0.0
	2204 - Homo sapiens, 789 aa.	1 . . . 770	504/780 (63%)
	[WO200153312-A1, 26-JUL-2001]
AAU28092	Novel human secretory protein, Seq	1 . . . 756	373/780 (47%)	0.0
	ID No 261 - Homo sapiens, 789 aa.	1 . . . 770	504/780 (63%)
	[WO200166689-A2, 13-SEP-2001]
AAB12448	Human hh00149 protein SEQ ID	20 . . . 756	368/760 (48%)	0.0
	NO: 4 - Homo sapiens, 785 aa.	17 . . . 766	497/760 (64%)
	[WO200031255-A1, 02-JUN-2000]

[0465] In a BLAST search of public sequence databases, the NOV30a protein was found to have homology to the proteins shown in the BLASTP data in Table 30E.

TABLE 30E
Public BLASTP Results for NOV30a
		NOV30a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96NI6	CDNA FLJ30803 FIS, CLONE	1 . . . 704	699/704 (99%)	0.0
	FEBRA2001245, WEAKLY	1 . . . 704	701/704 (99%)
	SIMILAR TO NAG14 - Homo
	sapiens (Human), 719 aa.
Q9ULH4	KIAA1246 PROTEIN - Homo	1 . . . 756	374/780 (47%)	0.0
	sapiens (Human), 832 aa (fragment).	44 . . . 813	505/780 (63%)
Q9BE71	HYPOTHETICAL 84.7 KDA	1 . . . 756	374/780 (47%)	0.0
	PROTEIN - Macaca fascicularis	1 . . . 770	503/780 (63%)
	(Crab eating macaque)
	(Cynomolgus monkey), 789 aa.
Q9CYK3	5730420O05RIK PROTEIN - Mus	1 . . . 756	378/783 (48%)	0.0
	musculus (Mouse), 788 aa.	1 . . . 769	506/783 (64%)
Q9P244	KIAA1484 PROTEIN - Homo	58 . . . 701	332/655 (50%)	e−177
	sapiens (Human), 700 aa (fragment).	1 . . . 631	441/655 (66%)

[0466] PFam analysis predicts that the NOV30a protein contains the domains shown in the Table 30F.

TABLE 30F
Domain Analysis of NOV30a
	NOV30a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
LRR	76 . . . 99	9/25 (36%)	0.49
		18/25 (72%)
LRR	100 . . . 123	8/25 (32%)	0.0031
		21/25 (84%)
LRR	148 . . . 171	11/25 (44%)	0.0021
		20/25 (80%)
LRR	172 . . . 195	7/25 (28%)	0.0035
		19/25 (76%)
LRRCT	240 . . . 285	21/54 (39%)	0.00023
		37/54 (69%)
ig	301 . . . 359	15/62 (24%)	1.4e−08
		41/62 (66%)
fn3	416 . . . 496	16/86 (19%)	0.066
		57/86 (66%)

Example 31

[0467] The NOV31 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 31A.

TABLE 31A
NOV31 Sequence Analysis
	SEQ ID NO: 89	1220 bp
NOV31a,	TCATGGCGCTGGCGGGCTTGGCCATGGGCTGCATCGACACCGTGGCCAGCATGCAGCT
CG108184-01
DNA Sequence	GGTAAGGATGTACCAGAAGGACTCGGCCGTCTTCCTCCAGGTGCTCCATTTCTTCGTG
	GGCTTTGGTGCTCTGCTGAGCCCCCTTATTGCTGACCCTTTCCTGTCTGAGGCCAACT
	GCTTGCCTGCCAATAGCACGGCCAACACCACCTCCCGAGGCCACCTGTTCCATGTCTC
	CAGGGTGCTGGGCCAGCACCACGTAGATGCCAAGCCTTGGTCCAACCAGACGTTCCCA
	GGGCTGACTCCAAAGGACGGGGCAGGGACCCGAGTGTCCTATGCCTTCTGGATCATGG
	CCCTCATCAATCTTCCAGTGCCCATGGCTGTGCTGATGCTGCTGTCCAAGGAGCGGCT
	GCTGACCTGCTGTCCCCAGAGGAGGCCCCTGCTTCTGTCTGCTGATGAGCTTGCCTTG
	GAGACACAGCCTCCTGAGAASGAAGATGCCTCCTCACTGCCCCCAAAGTTTCAGTCAC
	ACCTAGGTCATGAGGACCTGTTCAGCTGCTGCCAAAGGAAGAACCTCAGAGGAGCCCC
	TTATTCCTTCTTTGCCATCCACATCACGGGCGCCCTGGTACTGTTCATGACGGATGGG
	TTGACGGGTGCCTATTCCGCCTTCGTGTACAGCTATGCTGTGGAGAAGCCCCTGTCTG
	TGGGACACAAGGTGGCTGGCTACCTCCCCAGCCTCTTCTGGGGCTTCATCACACTGGG
	CCGGCTCCTCTCCATTCCCATATCCTCAAGAATGAAGCCGGCCACCATCGTTTTCATC
	AACGTGGTAGGCGTGGTGGTGACGTTCCTGGTGCTGCTTATTTTCTCCTACAACGTCG
	TGTTCCTGTTCGTGGGGACGGCAAGCCTGGGCCTGTTTCTCAGCAGCACCTTCCCCAG
	CATGCTGGCCTACACGGAGGACTCGCTGCAGTACAAAGGCTGTGCAACCACAGTGCTG
	GTGACAGGGGCAGGAGTTGGCGAGATGGTGCTGCAGATGCTGGTTGGTTCGATATTCC
	AGGCTCAGGGCAGCTATAGTTTCCTGGTCTGTGGCGTGATCTTTGCTTGTCTGGCTTT
	TACCTTCTATATCTTGCTCCTGTTTTTCCACAGGATGCACCCTGGACTCCCATCAGTT
	CCTACCCAAGACAGATCAATTGGAATGGAAAACTCTGAGTGCTACCAGAGGTAAAACT
	GG
	ORF Start: ATG at 3	ORF Stop: TAA at 1212
	SEQ ID NO: 90	403 aa	MW at 44063.2kD
NOV31a,	MALAGLAMGCIDTVANMQLVRMYQKDSAVFLQVLHFFVGFGALLSPLIADPFLSEANC
CG108184-01
Protein Sequence	LPANSTANTTSRGHLFHVSRVLGQHHVDAKPWSNQTFPGLTPKDGAGTRVSYAFWIMA
	LINLPVPMAVLMLLSKERLLTCCPQRRPLLLSADELALETQPPEKEDASSLPPKFQSH
	LGHEDLFSCCQRKNLRGAPYSFFAIHITGALVLFMTDGLTGAYSAFVYSYAVEKPLSV
	GHKVAGYLPSLFWGFITLGRLLSIPISSRMKPATMVFINVVGVVVTFLVLLIFSYNVV
	FLFVGTASLGLFLSSTFPSMLAYTEDSLQYKGCATTVLVTGAGVGEMVLQMLVGSIFQ
	AQGSYSFLVCGVIFGCLAFTFYILLLFFHRMHPGLPSVPTQDRSIGMENSECYQR
	SEQ ID NO: 91	1217 bp
NOV31b,	ATGGCGCTGGCGGGCTTGGCCATGGGCTGCATCGACACCGTGGCCAACATGCAGCAGG
CG108184-02
DNA SEQUENCE	TAAGGATGTACCAGAAGGACTCGGCCGTCTTCCTCCAGGTGCTCCATTTCTTCGTGGG
	CTTTGGTGCTCTGCTGAGCCCCCTTATTGCTGACCCTTTCCTGTCTGAGGCCAACTGC
	TTGCCTGCCAATAGCACGGCCAACACCACCTCCCGAGGCCACCTGTTCCATGTCTCCA
	GGGTGCTGGGCCAGCACCACGTAGATGCCAAGCCTTGGTCCAACCAGACGTTCCCAGG
	GCTGACTCCAAAGGACGGGGCAGGGACCCGAGTGTCCTATGCCTTCTGGATCATGGCC
	CTCATCAATCTTCCAGTGCCCATGGCTGTGCTGATGCTGCTGTCCAAGGAGCGGCTGC
	TGACCTGCTGTCCCCAGAGGAGGCCCCTGCTTCTGTCTGCTGATGAGCTTGCCTTGGA
	GACACAGCCTCCTGAGAAGGAAGATGCCTCCTCACTGCCCCCAAAGTTTCAGTCACAC
	CTAGGGCATGAGGACCTGTTCAGCTGCTGCCAAAGGAAGAACCTCAGAGGAGCCCCTT
	ATTCCTTCTTTGCCATCCACATCACGGCCGCCCTGGTCCTGTTCATGACGGATGGGTT
	GACGGGTGCCTATTCCGCCTTCGTGTACAGCTATGCTGTGGAGAAGCCCCTGTCTGTG
	GGACACAAGGTGGCTGGCTACCTCCCCAGCCTCTTCTGGGGCTTCATCACACTGGGCC
	GGCTCCTCTCCATTCCCATATCCTCAAGAATGAAGCCGGCCACCATGGTTTTCATCAA
	CGTGGTTGGCGTGGTGGTGACGTTCCTGGTGCTGCTTATTTTCTCCTACAACGTCGTC
	TTCCTGTTCGTGGGGACGGCAAGCCTGGGCCTGTTTCTCAGCAGCACCTTCCCCAGCA
	TGCTGGCCTACACGGAGGACTCGCTGCAGTACAAAGGCTGTGCAACCACAGTGCTGGT
	GACAGGGGCAGGAGTTGGCGAGATGGTGCTGCAGATGCTGGTTGGTTCGATATTCCAG
	GCTCAGGGCAGCTATAGTTTCCTGGTCTGTGGCGTGATCTTTGGTTGTCTGGCTTTTA
	CCTTCTATATCTTGCTCCTGTTTTTCCACAGGATGCACCCTGGACTCCCATCAGTTCC
	TACCCAAGACAGATCAATTGGAATGGAAAACTCTGAGTGCTACCAGAGGTAAAACTG
	ORF Start: ATG at 1	ORF Stop: TAA at 1210
	SEQ ID NO: 92	403 aa	MW at 44092.2kD
NOV31b,	MALAGLAMGCIDTVANMQQVRMYQKDSAVFLQVLHFFVGFGALLSPLIADPFLSEANC
CG108184-02
Protein Sequence	LPANSTANTTSRGHLFHVSRVLGQHHVDAKPWSNQTFPGLTPKDGAGTRVSYAFWIMA
	LINLPVPMAVLMLLSKERLLTCCPQRRPLLLSADELALETQPPEKEDASSLPPKFQSH
	LGHEDLFSCCQRKNLRGAPYSFFAIHITAALVLFMTDGLTGAYSAFVYSYAVEKPLSV
	GHKVAGYLPSLFWGFITLGRLLSIFISSRMKPATMVFINVVGVVVTFLVLLIFSYNVV
	FLFVGTASLGLFLSSTFPSMLAYTEDSLQYKGCATIWLVTGAGVGEMVLQMLVGSIFQ
	AQGSYSFLVCGVIFGCLAFTFYILLLFFHRMHPGLPSVPTQDRSIGMENSECYQR
	SEQ ID NO: 93	1190 bp
NOV31b,	ATGGCGCTGGCGGGCTTGGCCATGGGCTGCATCGACACCGTGGCCAACATGCAGCTGG
CG108184-03
DNA Sequence	TAAGGATGTACCAGAAGGACTCGGCCGTCTTCCTCCAGGTGCTCCATTTCTTCGTGGG
	CTTTGGTGCTCTGCTGAGCCCCCTTATTGCTGACCCTTTCCTGTCTGAGGCCAACTGC
	TTGCCTGCCAATAGCACGGCCAACACCACCTCCCGAGGCCACCTGTTCCATGTCTCCA
	GGGTGCTGGGCCAGCACCACGTAGATGCCAAGCCTTGGTCCAACCAGACGTTCCCAGG
	GCTGACTCCAAAGGACGGGGCAGGGACCCGAGTGTCCTATGCCTTCTGGATCATGGCC
	CTCATCAATCTTCCAGTGCCCATGGCTGTGCTGATGCTGCTGTCCAAGGAGCGGCTGC
	TGACCTGCTGTCCCCAGAGGAGGCCCCTGCTTCTGTCTGCTGATGAGCTTGCCTTGGA
	GACACAGCCTCCTGAGAAGGAAGATGCCTCCTCACTGCCCCCAAAGTTTCAGTCACAC
	CTAGGGCATGAGGACCTGTTCAGCTGCTGCCAAAGGAAGAACCTCAGAGGAGCCCCTT
	ATTCCTTCTTTGCCATCCACATCACGGGCGCCCTGGGTGCCTATTCCGCCTTCGTGTA
	CAGCTATGCTGTGGAGAAGCCCCTGTCTGTGGGACACAAGGTGGCTGGCTACCTCCCC
	AGCCTCTTCTGGGGCTTCATCACACTGGGCCGGCTCCTCTCCATTCCCATATCCTCAA
	GAATGAAGCCGGCCACCATGGTTTTCATCAACGTGGTTGGCGTGGTGGTGACGTTCCT
	GGTGCTGCTTATTTTCTCCTACAACGTCGTCTTCCTGTTCGTGGGGACGGCAAGCCTG
	GGCCTGTTTCTCAGCAGCACCTTCCCCAGCATGCTGGCCTACACGGAGGACTCGCTGC
	AGTACAAAGGCTGTGCAACCACAGTGCTGGTGACAGGGGCAGGAGTTGGCGAGATGGT
	GCTGCAGATGCTGGTTGGTTCGATATTCCAGGCTCAGGGCAGCTATAGTTTCCTGGTC
	TGTGGCGTGATCTTTGGTTGTCTGGCTTTTACCTTCTATACCTTGCTCCTGTTTTTCC
	ACAGGATGCACCCTGGACTCCCATCAGTTCCTACCCAAGACAGATCAATTGGAATGGA
	AAACTCTGAGTGCTACCAGAGGTAAAACTG
	ORF Start: ATG at 1	ORF Stop: TAA at 1183
	SEQ ID NO: 94	399 aa	MW at 43072.9kD
NOV31c,	MALAGLAMGCIDTVANMQLVRMYQKDSAVFLQVLHFFVGFGALLSPLIADPFLSEANC
CG108184-03
Protein Sequence	LPANSTANTTSRGHLFHVSRVLGQHHVDAKPWSNQTFPGLTPKDGAGTRVSYAFWIMA
	LINLPVPMAVLMLLSKERLLTCCPQRRPLLLSADELALETQPPEKEDASSLPPKFQSH
	LGHEDLFSCCQRKNLRGAPYSFFAIHITGALGAYSAFVYSYAVEKPLSVGHKVAGYLP
	SLFWGFITLGRLLSIPISSRMKPATMVFINVVGVVVTFLVLLIFSYNVVFLFVGTASL
	GLFLSSTFPSMLAYTEDSLQYKGCATTVLVTGAGVGEMVLQMLVGSIFQAQGSYSFLV
	CGVIFGCLAFTFYTLLLFFHRMHPGLPSVPTQDRSIGMENSECYQR

[0468] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 31B.

TABLE 31B
Comparison of NOV31a against NOV31b and NOV31c.
		NOV31a Residues/	Identities/Similarities
	Protein Sequence	Match Residues	for the Matched Region
	NOV31b	1 . . . 403	383/403 (95%)
		1 . . . 403	383/403 (95%)
	NOV31c	1 . . . 403	364/403 (90%)
		1 . . . 394	364/403 (90%)

[0469] Further analysis of the NOV31a protein yielded the following properties shown in Table 31C.

TABLE 31C
Protein Sequence Properties NOV31a
PSort     0.6000 probability located in plasma membrane; 0.4445
analysis: probability located in mitochondrial inner membrane; 0.4000
          probability located in Golgi body; 0.3000 probability
          located in endoplasmic reticulum (membrane)
SignalP   Cleavage site between residues 50 and 51
analysis:

[0470] A search of the NOV31a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 31D.

TABLE 31D
Geneseq Results for NOV31a
			Identities/
		NOV31a	Similarities
		Residues/	for the
Geneseq	Protein/Organism/Length [Patent	Match	Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAM24206	Human EST encoded protein SEQ ID	1 . . . 101	76/109 (69%)	9e−32
	NO: 1731 - Homo sapiens, 226 aa.	112 . . . 220	81/109 (73%)
	[WO200154477-A2, 02-AUG-2001]
AAY11034	H. pylori ORF	201 . . . 346	32/146 (21%)	0.35
	04ep41903_19689182_c1_43 inner	226 . . . 368	68/146 (45%)
	membrane protein - Helicobacter
	pylori, 407 aa. [WO9824475-A1, 11-JUN-1998]
AAY11033	H. pylori ORF	201 . . . 346	32/146 (21%)	0.35
	04ep41903_16667055_c1_37 inner	131 . . . 273	68/146 (45%)
	membrane protein - Helicobacter
	pylori, 312 aa. [WO9824475-A1, 11-JUN-1998]
ABB68766	Drosophila melanogaster polypeptide	212 . . . 371	39/168 (23%)	0.46
	SEQ ID NO: 33090 - Drosophila	582 . . . 746	71/168 (42%)
	melanogaster, 816 aa.
	[WO200171042-A2, 27-SEP-2001]
ABB48281	Listeria monocytogenes protein #985 -	250 . . . 356	32/117 (27%)	1.0
	Listeria monocytogenes, 402 aa.	62 . . . 172	52/117 (44%)
	[WO200177335-A2, 18-OCT-2001]

[0471] In a BLAST search of public sequence databases, the NOV31a protein was found to have homology to the proteins shown in the BLASTP data in Table 31E.

TABLE 31E
Public BLASTP Results for NOV31a
		NOV31a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9GM43	HYPOTHETICAL 44.1 KDA	1 . . . 403	397/403 (98%)	0.0
	PROTEIN - Macaca fascicularis	1 . . . 403	399/403 (98%)
	(Crab eating macaque)
	(Cynomolgus monkey), 403 aa.
CAD28481	HYPOTHETICAL 34.1 KDA	93 . . . 403	311/311 (100%)	e−180
	PROTEIN - Homo sapiens	1 . . . 311	311/311 (100%)
	(Human), 311 aa (fragment).
Q9D8I5	2010001E11RIK PROTEIN - Mus	205 . . . 375	49/171 (28%)	1e−13
	musculus (Mouse), 366 aa.	188 . . . 353	89/171 (51%)
Q8VCV9	SIMILAR TO RIKEN CDNA	205 . . . 375	46/171 (26%)	1e−12
	2010001E11 GENE - Mus	187 . . . 352	89/171 (51%)
	musculus (Mouse), 377 aa.
Q96PW9	KIAA1919 PROTEIN - Homo	205 . . . 353	44/149 (29%)	1e−12
	sapiens (Human), 403 aa	121 . . . 265	79/149 (52%)
	(fragment).

Example 32

[0472] The NOV32 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 32A.

TABLE 32A
NOV32 Sequence Analysis
	SEQ ID NO: 95	1557 bp
NOV32a,	CCCTGAGGAACAGACGTTCCCTGGCAGCCCTGGCACCTACAACCCCAGACATGCTGCT
CG10823 8-01
DNA Sequence	GCTGCTGCCCCTGCTCTGGGGGAGGGAGGGGGTGGAGGGACAGGGACAGCAAGAGAAT
	GGTTACACACTGCAAGTGCAGAGGGAGGTGAGGGTGCAGGAGGGCCTGTGTGTCCACG
	TGCCCTCCTCCTTCTCCCACCCCCAGGTTGCCTTGACTAACTCTCCCCAAGTTCATGG
	CTACTGGTTCCAGGAAGGGGCTGACACAGCCCAGGATGCTCCAATGGCTACGAACAAC
	CCAAAACGAAAAGTGAAGAAGGAGACCCAGGGCCGATTCCGTCTCTCTGGAAACCTGC
	AGATGAACGACTGCTCCCTGAGCATCGGAGACGCCAGGAGGAAGGACCAGGGGTCATT
	TTCTTTCTTTCGCATGGAGAGAGGAAGCATGAGATGGAATTACGCGTCTAACCAGCTC
	CACGTGTTGGTGACGGCCCTGACCCACAGGCCCAATATCTCCTCCCTGGGGACCATGG
	AGTCCGGCCGCCCGGGAAACCTGACCTGCTCTGTGTCCTGGGCCTGTGAGCAGGGGAT
	ACCCCTACCATCTATCTCCTGGATGGGGACCTCCGTGTCCTTCCCGGGCCGCACCACA
	GCCCGCTCCTCAGTGCTCACCCTCATCCCAAAGCCCCAGGACCATGGCACCAACCTCA
	CCTGTCAGGTGACCCTGCCTGAGGCTGGTGTGACCTTGACCAGGACTGTCCAATTCAA
	TGCGTCCGACCCTCCTCAGAACTTGACTGTGGCTATCTTCCAAGCAGACGGCACAGCA
	TCCACAGCCTTGGGGAACAGCTCATCCCTCTCAGTCCTGGAGGGCCAGTCTCTGCGCC
	TGGTCTGTGCTGTCGACAGCAATCCCCCTGCCAGGCTGAGCTGGACCCAAGGGAGCCT
	GACCCTGAGCCCCTCACAGTCCTCGAACCATGGGCTGCTGAAGCTGCCTCGAGTGCAC
	GCGAGGGATGAAGGGGAATTCACCTGCCGAGCTCAGAACCCTCGGGGCTCCCAGCACA
	TTTCCCTGAGCCTCTCCCTGCAGAATGAGGGCACAGGTACCACATGGCCTGTATCAGG
	AGTGATGCTGGGGGTGGTCGGGGGAGCTGGAGCCACAGCCCTGGTCTTCCTGTCCTTC
	TGCGTCATCTTCATCGTGGTGAGGTCCTGCAGGAAGAAATCAGCAAGGCCAGCAGCGG
	GCATCAGGGATATGGGCATGGAGGATGCAAACGCTGTCAGGGGCTCAGCCTATCAGCA
	GGGACCCCTGACTGAATCCTGGACAGACGGCAGCCCCCCGAAGCATCCTCCCATGGCT
	GCCTCCTCCTTAGGAGAAGGAGAGCTCCAGCATGCAACCCTCAGCTTCCATAAGGTCA
	GGCCTCAGAACGCGCAGGGACAGGAGGCCATGGACAGTGAATACTTGGAGATCAAGAT
	CCACAAGCGAGAAACTGCAGAGACTCGGGCCTGATTGGGGGATCACGGTCCCTCCAGG
	CAAAGGAGAAGTCAGAAGCTGATTCTTCTAAAATTAACAGCCCTCTAGA
	ORE Start: ATG at 51	ORF Stop: TGA at 1482
	SEQ ID NO: 96	477 aa	MW at 51555.7kD
NOV32a,	MLLLLPLLWGREGVEGQGQQENGYTLQVQREVRVQEGLCVHVPSSFSHPQVALTNSPQ
CG108238-01
Protein Sequence	VHGYWFQEGADTAQDAPMATNNPKRKVKKETQGRFRLSGNLQMNDCSLSIGDARRKDQ
	GSFSFFRMERGSMRWNYASNQLHVLVTALTHRPNISSLGTMESGRPGNLTCSVSWACE
	QGIPLPSISWMGTSVSFPGRTTARSSVLTLIPKPQDHGTNLTCQVTLPEAGVTLTRTV
	QFNASDPPQNLTVAIFQADGTASTALGNSSSLSVLEGQSLRLVCAVDSNPPARLSWTQ
	GSLTLSPSQSSNHGLLKLPRVHARDEGEFTCRAQNPRGSQHISLSLSLQNEGTGTTWP
	VSGVMLGVVGGAGATALVFLSFCVIFIVVRSCRKKSARPAAGIRDMGMEDANAVRGSA
	YQQGPLTESWTDGSPPKHPPMAASSLGEGELQHATLSFHKVRPQNAQGQEAMDSEYLE
	IKIHKRETAETRA

[0473] Further analysis of the NOV32a protein yielded the following properties shown in Table 32B.

TABLE 32B
Protein Sequence Properties NOV32a
PSort     0.7000 probability located in plasma membrane; 0.3000
analysis: probability located in microbody (peroxisome); 0.2000
          probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in
          mitochondrial inner membrane
SignalP   Cleavage site between residues 17 and 18
analysis:

[0474] A search of the NOV32a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 32C.

TABLE 32C
Geneseq Results for NOV32a
		NOV32a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB53288	Human polypeptide #28 - Homo	1 . . . 477	326/479 (68%)	e−180
	sapiens, 490 aa. [WO200181363-	5 . . . 476	374/479 (78%)
	A1, 01-NOV-2001]
AAE15809	Human sialoadhesin factor-3	1 . . . 469	317/469 (67%)	e−172
	(SAF-3) - Homo sapiens, 467 aa.	3 . . . 467	362/469 (76%)
	[WO200190193-A1, 29-NOV-2001]
AAW59992	Sialoadhesin family member-3	1 . . . 469	317/469 (67%)	e−172
	(SAF-3) - Homo sapiens, 467 aa.	3 . . . 467	362/469 (76%)
	[EP869178-A1, 07-OCT-1998]
AAB29188	Siglec 5 protein - Homo sapiens,	1 . . . 469	316/469 (67%)	e−171
	467 aa. [WO200053747-A1, 14-SEP-2000]	3 . . . 467	361/469 (76%)
AAU14582	Human novel protein #453 - Homo	1 . . . 469	316/469 (67%)	e−171
	sapiens, 467 aa. [WO200155437-	3 . . . 467	361/469 (76%)
	A2, 02-AUG-2001]

[0475] In a BLAST search of public sequence databases, the NOV32a protein was found to have homology to the proteins shown in the BLASTP data in Table 32D.

TABLE 32D
Public BLASTP Results for NOV32a
		NOV32a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
AAG00573	SIALIC ACID BINDING	1 . . . 477	351/485 (72%)	0.0
	IMMUNOGLOBULIN-LIKE	4 . . . 485	396/485 (81%)
	LECTIN 8 LONG SPLICE
	VARIANT - Homo sapiens
	(Human), 499 aa.
Q9Y286	QA79 MEMBRANE PROTEIN,	1 . . . 469	316/469 (67%)	e−170
	ALLELIC VARIANT AIRM-1B	3 . . . 467	361/469 (76%)
	PRECURSOR - Homo sapiens
	(Human), 467 aa.
Q9NYZ4	SIGLEC SAF2 - Homo sapiens	1 . . . 408	299/414 (72%)	e−168
	(Human), 431 aa.	4 . . . 415	338/414 (81%)
AAK51233	SIALIC ACID-BINDING	3 . . . 469	309/480 (64%)	e−167
	IMMUNOGLOBULIN-LIKE	1 . . . 477	355/480 (73%)
	LECTIN-LIKE SHORT SPLICE
	VARIANT - Homo sapiens
	(Human), 477 aa.
Q9BYI9	FOAP-9 - Homo sapiens (Human),	1 . . . 469	312/475 (65%)	e−167
	463 aa.	2 . . . 463	362/475 (75%)

[0476] PFam analysis predicts that the NOV32a protein contains the domains shown in the Table 32E.

TABLE 32E
Domain Analysis of NOV32a
	NOV32a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
ig	160 . . . 219	18/60 (30%)	0.023
		40/60 (67%)
ig	269 . . . 323	13/58 (22%)	1.7e−08
		45/58 (78%)

Example 33

[0477] The NOV33 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 33A.

TABLE 33A
NOV33 Sequence Analysis
	SEQ ID NO: 97	1494 bp
NOV33a,	TTTAATGCACAGATATAATACAGGAGTATGCTAGGTGGGTCTGTTTTTCAACTTGGAT
CG108695-01
DNA Sequence	CTCTCCTTACAGGGCTACTTTCTCATGTTTTGATGGAAGTCAAGAAGATACCAGTGGA
	AGAGGGGCTGTGCACTACAATCCCTTGTGCATTTGAATTTCCCAGAGAACCCCCAAGC
	AATTCCATGATCATGCACTACTGGCTCAACAAAAACATCAGCTCCCTGGTAGCTACAA
	ATAAACCCAATGCTACCATTGGTGATAACACCAAGGACAAATTTTACATGACTGGGAA
	TCTTGATGAAGAAGACTGTACCCTACTCATCCACGATATACTCAAAGGGAACAGCATA
	ACATATTTATTCTACGCAGATCTAGGAGAACAAAAAAGTGCTTTCCTGGGGGAGAATA
	TCAAACTTACCCAAAAGCCAGAGCTCCACATGCCAGAGATTCTTTTGCCTGAGAAGAC
	TGTGACCTTGAACTGTACCCTCAAAGGCACCTGCAAAGAAACCAAAGCCCTCTTCCAC
	TCCCGGAAGAACCCAGCCATCTCCAGCAGCTCCTCCTCGGTGCTGCACTTCACCCTGA
	GGCCTGAGGACCATGGCAACACCCTTGGATGTCACTTGAACTTATCCCTAGCCAACGT
	TTGTTCAATTCCTCTTGTTCCTTGGAGAAGACAGTTCTGTGCAGCTGTTCCTTCCACG
	GGATCCCCACGCCCTCCGTGCAGTGGTGGATGGGAGGTGTCCCTGTGGCTGTGAACAG
	CATGGATAACATCCTCCGGGTGACTTCTTCCACATGTGCCCCCTGGGCCAACAGCACC
	ATCAGCCTCATTGGGGAGCCAGAAAGAGTCATGAGACTTCACTGTGAGGGGAAGAACC
	AATATGGAATTCACACTTCCAGCATCTTCCTGCTTAGAATGAAGATGCTTACCTGGTG
	GGAGGAGCATCAGAGTCCCAAGGCCAAAGAAGGCTTGCCCCTTAAGAAACCAGAGCTG
	CTGGAGGAAACAGAAGTACCCAAAATGCCTGAAGCTGACACCCCACCAGACCGGGCTG
	GAGGTAAGTCCCTGGGACAGTCACAGGCAGACTGTCAAGCAACAGGGCCGCAGGCCAG
	GGCTCCCACCCCATCACCTGGCAGAACCCCGGGGAGGCACTTGTTCAGGACGGAGAGA
	CCCAGGCCCCCTCGCCCCACACAGCAGATGCTACATTTGCCAAAACAAAGCCCCACAG
	ACTGGGCGGCTTGAACGGCAGATACTGATTTTCTCCCCCTCTGGAGGCTGGAAATCCC
	AGGTCAAGGTGCCAGCAGCAGAGCTTCCTTCTGAGGCCTCTCACCTTGGCCGGTAGAT
	GCTGTCTTCTCCCTGTGTCCTCACAGGGTCATCCCTCTGCGTGTGCCTGGGTCCTAAT
	TTCCTTCCCTTGTAAGGACACCAGTCATTGAATTCAGGCCCATC
	ORF Start: ATG at 28	ORF Stop: TGA at 1288
	SEQ ID NO:98	420 aa	MW at 46435.0kd
NOV33a,	MLGGSVFQLGSLLTGLLSHVLMEVKKIPVEEGLCTTIPCAFEFPREPPSNSMIMHYWL
CG108695-01
Protein Sequence	NKNISSLVATNKPNATIGDNTKDKFYMTGNLDEEDCTLLIHDILKGNSITYLFYADLG
	EQKSAFLGENIKLTQKPELHMPEILLAEKTVTLNCTLKGTCKETKALFHSRKNPAISS
	SSSSVLHFTLRPEDHGNTLGCHLNLSLANVTRSSLVKLQVVCECWAPARLFNSSCSLE
	KTVLCSCSFHGIPTPSVQWWMGGVPVAVNSMDNILRVTSSTCAPWANSTISLIGEPER
	VMRLHCEGKNQYGIHTSSIFLLRMKMLTWWEEHQSPKAKEGLPLKKPELLEETEVPKM
	PEADTPPDRAGGKSLGQSQADCQATGPQARAPTPSPGRTPGRHLFRTERPRPPRPTQQ
	MLHLPKQSPTDWAA

[0478] Further analysis of the NOV33a protein yielded the following properties shown in Table 33B.

TABLE 33B
Protein Sequence Properties NOV33a
PSort     0.4500 probability located in cytoplasm; 0.3000 probability
analysis: located in microbody (peroxisome); 0.1000 probability located
          in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen)
SignalP   Cleavage site between residues 23 and 24
analysis:

[0479] A search of the NOV33a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 33C.

TABLE 33C
Geneseq Results for NOV33a
		NOV33a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAM00948	Human bone marrow protein, SEQ	25 . . . 232	69/226 (30%)	6e−21
	ID NO: 424 - Homo sapiens, 556	32 . . . 254	113/226 (49%)
	aa. [WO200153453-A2, 26-JUL-2001]
AAU14239	Human novel protein #110 - Homo	25 . . . 232	69/226 (30%)	6e−21
	sapiens, 551 aa. [WO200155437-	27 . . . 249	113/226 (49%)
	A2, 02-AUG-2001]
AAW55884	Human CD33-like protein - Homo	25 . . . 232	69/226 (30%)	6e−21
	sapiens, 551 aa. [WO9806733-A1,	27 . . . 249	113/226 (49%)
	19-FEB-1998]
AAB50907	Human PRO333 protein - Homo	25 . . . 224	67/216 (31%)	7e−21
	sapiens, 394 aa. [WO200073452-	25 . . . 237	108/216 (49%)
	A2, 07-DEC-2000]
AAB33462	Human PRO333 protein UNQ294	25 . . . 224	67/216 (31%)	7e−21
	SEQ ID NO: 249 −Homo sapiens,	25 . . . 237	108/216 (49%)
	394 aa. [WO200053758-A2, 14-SEP-2000]

[0480] In a BLAST search of public sequence databases, the NOV33a protein was found to have homology to the proteins shown in the BLASTP data in Table 33D.

TABLE 33D
Public BLASTP Results for NOV33a
		NOV33a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q95JN1	HYPOTHETICAL 34.6 KDA	85 . . . 359	244/315 (77%)	e−132
	PROTEIN - Macaca fascicularis	1 . . . 311	248/315 (78%)
	(Crab eating macaque)
	(Cynomolgus monkey), 312 aa.
Q9D4M0	4931406B18RIK PROTEIN - Mus	12 . . . 339	166/369 (44%)	1e−79
	musculus (Mouse), 367 aa.	11 . . . 359	216/369 (57%)
Q9D4Y7	4930538L19RIK PROTEIN - Mus	52 . . . 312	133/267 (49%)	1e−65
	musculus (Mouse), 283 aa.	1 . . . 247	173/267 (63%)
AAD50978	SIALIC ACID BINDING IG-LIKE	25 . . . 232	69/226 (30%)	1e−20
	LECTIN-5 - Homo sapiens	27 . . . 249	113/226 (49%)
	(Human), 551 aa.
O15389	OB BINDING PROTEIN-2	25 . . . 232	69/226 (30%)	1e−20
	(SIGLEC5) - Homo sapiens	27 . . . 249	113/226 (49%)
	(Human), 551 aa.

Example 34

[0481] The NOV34 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 34A.

TABLE 34A
NOV34 Sequence Analysis
	SEQ ID NO:99	1152 bp
NOV34a,	TGGGACCACGTGGGATGCTGCCGTGGCTTCTTGTCTTCTCTGCTCTGGGTCTCCAGG
CG109505-01
DNA Sequence	CCTGGGGTTCTTTCTCCTGGAGTGAGACCCAAGCCAGAGGCTTGTCCCAGAGGCTTAT
	GGACCTGTTTGTCAGCATCTCACAGTTCATTCACAAGGATACTCCCACCATCGTCTCC
	CGCAAGGAGTGGGGGGCAAGACCGCTCGCCTGCAGGGCCCTGCTGACCCTGCCTGTGG
	CCTACATCATCACAGACCAGCTCCCAGGGATGCAGTGCCAGCAGCAGAGCGTTTGCAG
	CCAGATGCTGCGGGGGTTGCAGTCCCATTCCGTCTACACCATAGGCTGGTGCGACGTG
	GCGTACAGCTTCCTGGTTGGGGATGATGGCAGGGTGTATGAAGGTGTTGGCTGGAACA
	TCCAAGGCTTGCACACCCAGGGCTACAACAACATTTCCCTGGGCATCGCCTTCTTTGG
	CAATAAGAAGGGTCACTCCCCCAGCCCTGCTGCCTTATCAGCTGCAGAGGGTCTGATC
	TCCTATGCCATCCAGAAGGGTCACCTGTCGCCCAGGTATATTCAGCCACTTCTTCTGA
	AAGAAGAGACCTGCCTGGACCCTCAACATCCAGTGATGCCCAGGAAGCAGCTTGCCCC
	GGCGTTGTCCCACGGTCTGTGTGGGGAGCCAGGGAGACCCTTATCAAAAATGAACCTC
	CCAGCCAAATATGTCATCATCATCCACACCGCTGGCACAAGCTGCACTGTATCCACAG
	ACTGCCAGACTGTCGTCCGAAACATACAGTCCTTTCACATGGACACACGGAACTTTTG
	TGACATTGGATATAGCTTCCTGGTGGGCCAGGATGGTGGCGTGTATGAAGGGGTTGGA
	TGGCACATCCAAGGCTCTCACACTTATGGATTCAACGATATTGCCCTAGGAATTGCCT
	TCATCGGCATCCCCTACTTTGTAGGTCCAAATGCTGCAGCGCTGGAGGCGGCCCAGGA
	CCTGATCCAGTGTGCCGTGGTTGAGGGGTACCTGACTCCAAACTACCTGCTGATGGGC
	CACAGTGACGTGGTCAACATCCTGTCCCCTGGGCAGGCTTTGTATAACATCATCAGCA
	CCTGGCCTCATTTCAAGCACTGAAGGAGGCCCCACTCCCTTTGAGACTGC
	ORF Start: ATG at 16	ORF Stop: TGA at 1123
	SEQ ID NO: 100	369 aa	MW at 40411.0kd
NOV34a,	MLPWLLVFSALGLQAWGSFSWSETQARGLSQRLMDLFVSISQFIHKDTPTIVSRKEWG
CG109505-01
Protein Sequence	ARPLACRALLTLPVAYIITDQLPGMQCQQQSVCSQMLRGLQSHSVYTIGWCDVAYSFL
	VGDDGRVYEGVGWNIQGLHTQGYNNISLGIAFFGNKKGHSPSPAALSAAEGLISYAIQ
	KGHLSPRYIQPLLLKEETCLDPQHPVMPRKQLAPALSHGLCGEPGRPLSKMNLPAKYV
	IIIHTAGTSCTVSTDCQTVVRNIQSFHMDTRNFCDIGYSFLVGQDGGVYEGVGWHIQG
	SHTYGFNDIALGIAFIGIPYFVGPNAAALEAAQDLIQCAVVEGYLTPNYLLMGHSDVV
	NILSPGQALYNIISTWPHFKH

[0482] Further analysis of the NOV34a protein yielded the following properties shown in Table 34B.

TABLE 34B
Protein Sequence Properties NOV34a
PSort     0.3894 probability located in outside; 0.1213 probability
analysis: located in microbody (peroxisome); 0.1000 probability located
          in endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 18 and 19
analysis:

[0483] A search of the NOV34a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 34C.

TABLE 34C
Geneseq Results for NOV34a
		NOV34a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAY96963	Wound healing tissue peptidoglycan	1 . . . 369	252/369 (68%)	e−150
	recognition protein-like protein -	1 . . . 368	295/369 (79%)
	Homo sapiens, 368 aa.
	[WO200039327-A1, 06-JUL-2000]
ABB53272	Human polypeptide #12 - Homo	1 . . . 369	236/369 (63%)	e−140
	sapiens, 369 aa. [WO200181363-	1 . . . 369	282/369 (75%)
	A1, 01-NOV-2001]
AAE00693	Human full length granulocyte	1 . . . 369	236/369 (63%)	e−140
	peptide homolog Zgpa1 protein #2 -	1 . . . 369	282/369 (75%)
	Homo sapiens, 369 aa.
	[WO200129224-A2, 26-APR-2001]
AAE00692	Human full length granulocyte	1 . . . 369	235/375 (62%)	e−137
	peptide homolog Zgpa1 protein #1 -	1 . . . 375	282/375 (74%)
	Homo sapiens, 375 aa.
	[WO200129224-A2, 26-APR-2001]
AAY76124	Human secreted protein encoded by	2 . . . 270	213/269 (79%)	e−118
	gene 1 - Homo sapiens, 244 aa.	4 . . . 242	215/269 (79%)
	[WO9958660-A1, 18-NOV-1999]

[0484] In a BLAST search of public sequence databases, the NOV34a protein was found to have homology to the proteins shown in the BLASTP data in Table 34D.

TABLE 34D
Public BLASTP Results for NOV34a
		NOV34a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96LB9	PEPTIDOGLYCAN	2 . . . 369	309/370 (83%)	e−175
	RECOGNITION PROTEIN-I-	4 . . . 341	311/370 (83%)
	ALPHA PRECURSOR - Homo
	sapiens (Human), 341 aa.
Q9HD75	HYPOTHETICAL 40.0 KDA	1 . . . 369	252/369 (68%)	e−149
	PROTEIN - Homo sapiens	1 . . . 368	295/369 (79%)
	(Human), 368 aa.
CAC38715	SEQUENCE 7 FROM PATENT	1 . . . 369	236/369 (63%)	e−140
	WO0129224 - Homo sapiens	1 . . . 369	282/369 (75%)
	(Human), 369 aa.
Q96LB8	PEPTIDOGLYCAN	1 . . . 369	237/373 (63%)	e−138
	RECOGNITION PROTEIN-I-	1 . . . 373	282/373 (75%)
	BETA PRECURSOR - Homo
	sapiens (Human), 373 aa.
CAC38714	SEQUENCE 4 FROM PATENT	1 . . . 369	235/375 (62%)	e−137
	WO0129224 - Homo sapiens	1 . . . 375	282/375 (74%)
	(Human), 375 aa.

Example 35

[0485] The NOV35 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 35A.

TABLE 35A
NOV35 Sequence Analysis
	SEQ ID NO: 101	3950 bp
NOV35a,	ATGCGCGGGGCGGGGGCGGCGGGGCTGCTGGCGCTGCTGCTGCTGCTGCTGCTGCTGC
CG109742-01
Protein Sequence	TGCTGGGCCTGGGCGGCAGGGTCGAGGGGGGGCCGGCCGGCGAGCGGGGCGCAGGCGG
	GGGCGGGGCGCTGGCCCGCGAGCGCTTCAAGGTGGTCTTTGCGCCGGTGATCTGCAAG
	CGGACCTGTCTCAAGGGCCAGTGTCGGGACAGTTGTCAGCAGGGCTCCAACATGACGC
	TCATCGGAGAGAACGGCCACAGCACAGACACGCTCACGGGCTCCGGCTTCCGCGTGGT
	GGTGTGCCCTCTCCCCTGCATGAATGGCGGCCAGTGCTCCTCGCGAAACCAGTGCCTG
	TGTCCCCCGGACTTCACTGGGCGCTTCTGCCAGGTGCCCGCAGGAGGAGCCGGTGGGG
	GTACCGGCGGCTCAGGCCCCGGCCTGAGCAGGACAGGGGCCCTGTCCACAGGGGCGCT
	GCCGCCCCTGGCTCCGGAGGGCGACTCTGTGGCCAGCAAGCACGCCATCTACGCCGTC
	CAGGTGATCGCTGACCCTCCTGGGCCCGGGGAGGGGCCTCCTGCCCAGCACGCAGCCT
	TCCTGGTGCCCCTAGGCCCGGGACAGATCTCAGCAGAAGTGCAGGCCCCGCCCCCCGT
	GGTGAATGTGCGCGTCCATCACCCGCCCGAGGCCTCAGTCCAGGTGCACCGCATTGAG
	AGCTCGAACGCCGAGAGCGCAGCCCCCTCCCAGCACCTGCTGCCGCACCCCAAGCCCT
	CGCACCCCCGGCCGCCCACCCAGAAGCCCCTGGGCCGCTGCTTTCAGGACACTCTGCC
	CAAGCAGCCGTGTGGCAGCAACCCCCTCCCCGGCCTCACCAAGCAGGAAGACTGCTGC
	GGTAGCATCGGCACTGCCTGGGGCCAGAGCAAGTGCCACAAGTGTCCCCAGCTGCAGT
	ACACAGGAGTGCAGAAGCCAGGGCCTGTACGTGGGGAAGTGGGCGCTGACTGTCCCCA
	GGGCTACAAGAGGCTTAACAGCACCCACTGCCAGGACATCAACGAGTGCGCAATGCCG
	GGCGTGTGTCGCCATGGTGACTGCCTCAACAACCCTGGCTCCTATCGCTGTGTCTGCC
	CACCTGGCCATAGTTTAGGCCCCTCCCGTACACAGTGCATTGCAGACAAACCGGAGGA
	GAAGAGCCTGTGTTTCCGCCTGGTGAGCCCTGAGCACCAGTGCCAGCACCCACTGACC
	ACCCGCCTGACCCGCCAGCTCTGCTGCTGCAGTGTCGGCAAGGCCTGGGGCGCGCGGT
	GTCAGCGCTGCCCAACAGATGGCACCGCTGCGTTCAAGGAGATCTGCCCAGCTGGGAA
	GGGATACCACATTCTCACCTCCCACCAGACGCTCACCATTCAGGGCGACAGTGACTTT
	TCCCTTTTCCTGCACCCTGACGGGCCACCCAAGCCCCAGCAGCTTCCGGAGAGCCCTA
	GCCAGGCTCCACCACCTGAGGACACAGAGGAAGAGAGAGGGGTGACCACGGACTCACC
	GGTGAGTGAGGAGAGGTCAGTGCAGCAGAGCCACCCAACTGCCACCACGACTCCTGCC
	CGGCCCTACCCCGAGCTGATCTCCCGTCCCTCGCCCCCGACCATGCGCTGGTTCCTGC
	CGGACTTGCCTCCTTCCCGCAGCGCCGTAGAGATCGCTCCCACTCAGGTCACAGAGAC
	TGATGAGTGCCGACTGAACCAGAACATCTGTGGCCACGGAGAGTGCGTGCCGGGCCCC
	CCTGACTACTCCTGCCACTGCAACCCCGGCTACCGGTCACATCCCCAGCACCGCTACT
	GCGTGGATGTGAACGAGTGCGAGGCAGAGCCCTGTGGCCCGGGGAGGGGCATCTGCAT
	GAACACCGGCGGCTCCTACAATTGCCACTGCAACCGCGGCTACCGCCTGCACGTGGGC
	GCCGGGGGGCGCTCGTGCGTGGACCTGAACGAATGCGCCAAGCCCCACCTGTGCGGCG
	ACGGCGGCTTCTGCATCAACTTTCCCGGTCACTACAAGTGCAACTGCTACCCCGGCTA
	CCGGCTCAAAGCCTCCCGGCCTCCTGTGTGCGAAGACATCGACGAGTGCCGGGACCCA
	AGCTCTTGCCCGGATGGCAAATGCGAGAACAAGCCCGGGAGCTTCAAGTGCATCGCCT
	GTCAGCCTGGCTGGTGCGAGAACCTCCCGGGCTCCTTCCGCTGCACCTGTGCCCAGGG
	CTACGCGCCCGCGCCCGACGGCCGCAGTTGCTTGGATGTGGACGAGTGTGAGGCTGGG
	GACGTGTGTGACAATGGCATCTGCAGCAACACGCCAGGATCTTTCCAGTGTCAGTGCC
	TCTCTGGCTACCATCTGTCCAGGGACCGGAGCCACTGCGAGGACATTGATGAGTGTGA
	CTTCCCTGCAGCCTGCATTGGGGGTGACTGCATCAATACCAATGGCTCCTACAGATGT
	CTTTGCCCCCAGGGGCATCGGCTGGTGGGTGGCAGGAAATGCCAAGACATAGATGAGT
	GCAGCCAGGACCCGAGCCTGTGCCTTCCCCATGGGGCCTGCAAGAACCTTCAGGGCTC
	CTATGTGTGTGTCTGCGATGAGGGCTTCACTCCCACCCAGGACCAGCACGGTTGTGAG
	GAGGTGGAGCAGCCCCACCACAAGAAGGAGTGCTACCTGAACTTCGATGACACAGTGT
	TCTGCGACAGCGTATTGGCCACCAACGTGACCCAGCAGGAGTGCTGCTGCTCTCTGGG
	GGCCGGCTGGGGCGACCACTGCGAAATCTACCCCTGCCCAGTCTACAGCTCAGCCGAG
	TTCCACAGCCTCTGCCCAGACGGAAAGGGCTACACCCAGGACAACAACATCGTCAACT
	ACGGCATCCCAGCCCACCGTGACATCGACGAGTGCATGTTGTTCGGGTCGGAGATTTG
	CAAGGAGGGCAAGTGCGTGAACACGCAGCCTGGCTACGAGTGCTACTGCAAGCAGGGC
	TTCTACTACGACGGGAACCTGCTGGAATGCGTGGACGTGGACGAGTGCCTGGACGAGT
	CCAACTGCCGGAACGGAGTGTGTGAGAACACGCGCGGCGGCTACCGCTGTGCCTGCAC
	GCCCCCTGCCGAGTACAGTCCCGCGCAGCGCCAGTGCCTGAGCCCGGAAGAGATGGAG
	CGTGCCCCGGAGCGGCGCGACGTGTGCTGGAGCCAGCGCGGAGAGGACGGCATGTGCG
	CTGGCCCCCTGGCCGGGCCTGCCCTCACCTTCGACGACTGCTGCTGCCGCCAGGGCCG
	CGGCTGGGGCGCCCAATGCCGACCGTGCCCGCCGCGCGGCGCGGGGTCCCATTGCCCG
	ACATCGCAGAGCGAGAGCAATTCCTTCTGGGACACAAGCCCCCTGCTGTTGGGGAAGC
	CCCCAAGAGATGAGGACAGTTCAGAGGAGGATTCAGACGAGTGTCGCTGCGTGAGTGG
	GACGCCTCCCGCGCCCGCTGCGTGGATATCGACGAGTGCCGAGAGCTGAACCAGCGCG
	GGCTGCTGTGCAAGAGCGAGCGCTGCGTGAACACCAGCGGCTCCTTCCGCTGCGTCTG
	CAAAGCCGGCTTCGCGCGCAGCCGCCCGCACGGGGCCTGCGTTCCCCAGCGCCGCCGC
	TGACGCCGCCGACGCCGCCCTCGGCCCAGACCTCGGTGATCACTGAGGGATTTCCGCG
	AGCTCGGCCTCACTTCTGCCCCGACTTGTGGCTCGGACCCAGGGACCTTCAGGGCCCG
	CAGACCCTCCCGGCGCCTTGAGACCCGAGGCGCCCCTACCGGCCCCCCTCCCCGGTTA
	GCGGGCGGTTGTAAGGTCTCCGGCGGGCGCTGCCTGCCTTCCTCCCAGAGGGTGTTTC
	AAAAAA
	ORF Start: TG at 1	ORF Stop: TGA at 3655
	SEQ ID NO: 102	1218 aa	MW at 130645.3kD
NOV35a,	MRGAGAAGLLALLLLLLLLLLGLGGRVEGGPAGERGAGGGGALARERFKVVFAPVICK
CG109742-01
Protein Sequence	RTCLKGQCRDSCQQGSNMTLIGENGHSTDTLTGSGFRVVVCPLPCMNGGQCSSRNQCL
	CPPDFTGRFCQVPAGGAGGGTGGSGPGLSRTGALSTGALPPLAPEGDSVASKHAIYAV
	QVIADPPGPGEGPPAQHAAFLVPLGPGQISAEVQAPPPVVINRVHHPPEASVQVHRIE
	SSNAESAAPSQHLLPHPKPSHPRPPTQKPLGRCFQDTLPKQPCGSNPLPGLTKQEDCC
	GSIGTAWGQSKCHKCPQLQYTGVQKPGPVRGEVGADCPQGYKRLNSTHCQDINECAMP
	GVCRHGDCLNNPGSYRCVCPPGHSLGPSRTQCIADKPEEKSLCFRLVSPEHQCQHPLT
	TRLTRQLCCCSVGKAWGARCQRCPTDGTAAFKEICPAGKGYHILTSHQTLTIQGESDF
	SLFLHPDGPPKPQQLPESPSQAPPPEDTEEERGVTTDSPVSEERSVQQSHPTATTTPA
	RPYPELISRPSPPTMRWFLPDLPPSRSAVEIAPTQVTETDECRLNQNICGHGECVPGP
	PDYSCHCNPGYRSHPQHRYCVDVNECEAEPCGPGRGICMNTGGSYNCHCNRGYRLHVG
	AGGRSCVDLNECAKPHLCGDGGFCINFPGHYKCNCYPGYRLKASRPPVCEDIDECRDP
	SSCPDGKCENKPGSFKCIACQPGWCENLPGSFRCTCAQGYAPAPDGRSCLDVDECEAG
	DVCDNGICSNTPGSFQCQCLSGYHLSRDRSHCEDIDECDFPAACIGGDCINTNGSYRC
	LCPQGHRLVGGRKCQDIDECSQDPSLCLPHGACKNLQGSYVCVCDEGFTPTQDQHGCE
	EVEQPHHKKECYLNFDDTVFCDSVLATNVTQQECCCSLGAGWGDHCEIYPCPVYSSAE
	FHSLCPDGKGYTQDNNIVNYGIPAHRDIDECMLFGSEICKEGKCVNTQPGYECYCKQG
	FYYDGNLLECVDVDECLDESNCRNGVCENTRGGYRCACTPPAEYSPAQRQCLSPEEME
	RAPERRDVCWSQRGEDGMCAGPLAGPALTFDDCCCRQGRGWGAQCRPCPPRGAGSHCP
	TSQSESNSFWDTSPLLLGKPPRDEDSSEEDSDECPCVSGRCVPRPGGAVCECPGGFQL
	DASEARCVDIDECRELNQRGLLCKSERCVNTSGSFRCVCKAGFARSRPHGACVPQRRR
	SEQ ID NO: 103	603 bp
NOV3 5b,	GGATCCCGCTTCAAGGTGGTCTTTGCGCCGGTGATCTGCAAGCGGACCTGTCTCAAGG
207639410 DNA
Sequence	GCCAGTGTCGGGACAGTTGTCAGCAGGGCTCCAACATGACGCTCATCGGAGAGAACGG
	CCACAGCACAGACACGCTCACGGGCTCCGGCTTCCGCGTGGTGGTGTGCCCTCTCCCC
	TGCATGAATGGCGGCCAGTGCTCCTCGCGAAACCAGTGCCTGTGTCCCCCGGACTTCA
	CTGGGCGCTTCTGCCAGGTGCCCGCAGGAGGAGCCGGTGGGGGTACCGGCGGCTCAGG
	CCCCGGCCTGAGCAGGACAGGGGCCCTGTCCACAGGGGCGCTGCCGCCCCTGGCTCCG
	GAGGGCGGCTCTGTGGCCAGCAAGCACGCCATCTACGCCGTCCAGGTGATCGCTGACC
	CTCCTGGGCCCGGGGAGGGGCCTCCTGCCCAGCACGCAGCCTTCCTGGTGCCCCTAGG
	CCCGGGACAGATCTCAGCAGAAGTGCAGGCCCCGCCCCCCGTGGTGAATGTGCGCGTC
	CATCACCCGCCCGAGGCCTCAGTCCAGGTGCACCGCATTGAGAGCTCGAACGCCGAGA
	GCGCAGCCCCCTCCCAGCTCGAG
	ORE Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 104	201 aa	MW at 20294.8kD
NOV35b,	GSRFKVVFAPVICKRTCLKGQCRDSCQQGSNMTLIGENGHSTDTLTGSGFRVVVCPLP
207639410
Protein Sequence	CMNGGQCSSRNQCLCPPDFTGRFCQVPAGGAGGGTGGSGPGLSRTGALSTGALPPLAP
	EGGSVASKRAIYAVQVIADPPGPGEGPPAQHAAFLVPLGPGQISAEVQAPPPVVNVRV
	HHPPEASVQVHRIESSNAESAAPSQLE
	SEQ ID NO: 105	603 bp
NOV35c,	GGATCCCGCTTCAAGGTGGTCTTTGCGCCGGTGATCTGCAAGCGGACCTGTCTCAAGG
207639427 DNA
Sequence	GCCAGTGTCGGGACAGTTGTCAGCAGGGCTCCAACATGACGCTCATCGGAGAGAACGG
	CCACAGCACAGACACGCTCACGGGCTCCGGCTTCCGCGTGGTGGTGTGCCCTCTCCCC
	TGCATGAATGGCGGCCAGTGCTCCTCGCGAAACCAGTGCCTGTGTCCCCCGGACTTCA
	CTGGGCGCTTCTGCCAGGTGCCCGCAGGAGGAGCCGGTGGGGGTACCGGCGGCTCAGG
	CCCCGGCCTGAGCAGGACAGGGGCCCTGTCCACAGGGGCGCTGCCGCCCCTGGCTCCG
	GAGGGCGACTCTGTGGCCAGCACGCACGCCATCTACGCCGTCCAGGTGATCGCTGACC
	CTCCTGGGCCCGGGGAGGGGCCTCCTGCCCAGCACGCAGCCTTCCTGGTGCCCCTAGG
	CCCGGGACAGATCTCAACAGAAGTGCAGGCCCCGCCCCCCGTGGTGAATGTGCGCGTC
	CATCACCCGCCCGAGGCCTCAGTCCAGGTGCACCGCATTGAGAGCTCGAACGCCGAGA
	GCGCAGCCCCCTCCCAGCTCGAG
	ORE Start: at 1	ORE Stop: end of Sequence
	SEQ ID NO: 106	201 aa	MW at 20382.9kD
NOV35c,	GSRFKVVFAPVICKRTCLKGQCRDSCQQGSNMTLIGENGHSTDTLTGSGFRVVVCPLP
207639427
Protein Sequence	CMNGGQCSSRNQCLCPPDFTGRFCQVPAGGAGGGTGGSGPGLSRTGALSTGALPPLAP
	EGDSVASKHAIYAVQVIADPPGPGEGPPAQHAAFLVPLGPGQISTEVQAPPPVVNVRV
	HHPPEASVQVHRIESSNAESAAPSQLE
	SEQ ID NO: 107	603 bp
NOV35d,	GGATCCCGCTTCAAGGTGGTCTTTGCGCCGGTGATCTGCAAGCGGACCTGTCTCAAGG
2O7639438 DNA
Sequence	GCCAGTGTCGGGACAGTTGTCCGCAGGGCTCCAACATGACGCTCATCGGAGAGAACGG
	CCACAGCACAGACACGCTCACGGGCTCCGGCTTCCGCGTGGTGGTGTGCCCTCTCCCC
	TGCACGAATGGCGGCCAGTGCTCCTCGCGAAACCAGTGCCTGTGTCCCCCGGACTTCA
	CTGGGCGCTTCTGCCAGGTGCCCGCAGGAGGAGCCGGTGGGGGTACCGGCGGCTCAGG
	CCCCGGCCTGAGCAGGACAGGGGCCCTGTCCACAGGGGCGCTGCCGCCCCTGGCTCCG
	GAGGGCGACTCTGTGGCCAGCAAGCACGCCATCTACGCCGTCCAGGTGATCGCTGACC
	CTCCTGGGCCCGGGGAGGGGCCTCCTGCCCAGCACGCAGCCTTCCTGGTGCCCCTAGG
	CCCGGGACAGATCTCAGCAGAAGTGCAGGCCCCGCCCCCCGTGGTGAATGTGCGCGTC
	CATCACCCGCCCGAGGCCTCAGTCCAGGTGCACCGCATTGAGAGCTCGAACGCCGAGA
	GCGCAGCCCCCTCCCAGCTCGAG
	ORF Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 108	201 aa	MW at 20291.7kD
NOV35d,	GSRFKVVFAPVICKRTCLKGQCRDSCPQGSNMTLIGENGHSTDTLTGSGFRVVVCPLP
207639438
Protein Sequence	CTNGGQCSSRNQCLCPPDFTGRFCQVPAGGAGGGTGGSGPGLSRTGALSTGALPPLAP
	EGDSVASKHAIYAVQVIADPPGPGEGPPAQHAAFLVPLGPGQISAEVQAPPPVVNVRV
	HHPPEASVQVHRIESSNAESAAPSQLE
	SEQ ID NO: 109	603 bp
NOV35e,	GGATCCCGCTTCAAGGTGGTCTTTGCGCCGGTGATCTGCAAGCGGACCTGTCTCGAGG
207639448 DNA
Sequence	GCCAGTGTCGGGACAGTTGTCAGCAGGGCTCCAACATGACGCTCATCGGAGAGAACGG
	CCACAGCACAGACACGCTCACGGGCTCCGGCTTCCGCGTGGTGGTGTGCCCTCTCCCC
	TGCATGAATGGCGGCCAGTGCTCCTCGCGAAACCAGTGCCTGTGTCCCCCGGACTTCA
	CTGGGCGCTTCTGCCAGGTGCCCGCAGGAGGAGCCGGTGGGGGTACCGGCGGCTCAGG
	CCCCGGCCTGAGCAGGACAGGGGCCCTGTCCACAGGGGCGCTGCCGCCCCTGGCTCCG
	GAGGGCGACTCTGTGGCCAGCAAGCACGCCATCTACGCCGTCCAGGTGATCGCTGACC
	CTCCTGGGCCCOGGGAGGGGCCTCCTGCCCAGCACGCAGCCTTCCTGGTGCCCCTAGG
	CCCGGGACAGATCTCAGCAGAAGTGCAGGCCCCGCCCCCCGTGGTGAATGTGCGCGTC
	CATCACCCGCCCGAGGCCTCAGTCCAGGTGCACCGCATTGAGAGCTCGAACGCCGAGA
	GCGCAGCCCCCTCCCAGCTCGAG
	ORF Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 110	201 aa	MW at 20353.8kD
NOV35e,	GSRFKVVFAPVICKRTCLEGQCRDSCQQGSNMTLIGENGHSTDTLTGSGRFVVVCPLP
207639448
Protein Sequence	CMNGGQCSSRNQCLCPPDFTGRFCQVPAGGAGGGTGGSGPGLSRTGALSTGALPPLAP
	EGDSVASKHAIYAVQVIADPPGPGEGPPAQHAAFLVPLGPGQISAEVQAPPPVVNVRV
	HHPPEASVQVHRIESSNAESAAPSQLE

[0486] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 35B.

TABLE 35B
Comparison of NOV35a against NOV35b through NOV35e.
	NOV35a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV35b	47 . . . 243	154/197 (78%)
	3 . . . 199	154/197 (78%)
NOV35c	47 . . . 243	154/197 (78%)
	3 . . . 199	154/197 (78%)
NOV35d	47 . . . 243	153/197 (77%)
	3 . . . 199	153/197 (77%)
NOV35e	47 . . . 243	154/197 (78%)
	3 . . . 199	155/197 (78%)

[0487] Further analysis of the NOV35a protein yielded the following properties shown in Table 35C.

TABLE 35C
Protein Sequence Properties NOV35a
PSort     0.8200 probability located in outside; 0.1900 probability
analysis: located in lysosome (lumen); 0.1000 probability located in
          endoplasmic reticulum (membrane); 0.1000 probability
          located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 30 and 31
analysis:

[0488] A search of the NOV35a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 35D.

TABLE 35D
Geneseq Results for NOV35a
		NOV35a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB61419	Human TANGO 275 protein -	1 . . . 1218	1217/1289 (94%)	0.0
	Homo sapiens, 1289 aa.	1 . . . 1289	1217/1289 (94%)
	[WO200100672-A1, 04-JAN-2001]
AAY70551	Human latent transforming growth	35 . . . 1218	1183/1208 (97%)	0.0
	factor-beta binding protein 3 (I) -	1 . . . 1208	1183/1208 (97%)
	Homo sapiens, 1208 aa.
	[WO200012551-A1, 09-MAR-2000]
AAY70554	Human latent transforming growth	35 . . . 1218	1183/1257 (94%)	0.0
	factor-beta binding protein 3 (III) -	1 . . . 1257	1183/1257 (94%)
	Homo sapiens, 1257 aa.
	[WO200012551-A1, 09-MAR-2000]
AAB61483	Human TANGO 300 extracellular	10 . . . 1213	1056/1230 (85%)	0.0
	domain - Homo sapiens, 1251 aa.	6 . . . 1229	1078/1230 (86%)
	[WO200100672-A1, 04-JAN-2001]
AAR79475	Mouse LTBP-3 - Mus sp, 1251 aa.	10 . . . 1213	1056/1230 (85%)	0.0
	[WO9522611-A2, 24-AUG-1995]	6 . . . 1229	1078/1230 (86%)

[0489] In a BLAST search of public sequence databases, the NOV35a protein was found to have homology to the proteins shown in the BLASTP data in Table 35E.

TABLE 35E
Public BLASTP Results for NOV35a
		NOV35a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9NS15	LATENT TRANSFORMING	1 . . . 1218	1218/1242 (98%)	0.0
	GROWTH FACTOR BETA	15 . . . 1256	1218/1242 (98%)
	BINDING PROTEIN 3 - Homo
	sapiens (Human), 1256 aa.
Q9H7K2	FLJ00070 PROTEIN - Homo	1 . . . 1218	1217/1289 (94%)	0.0
	sapiens (Human), 1382 aa	95 . . . 1382	1217/1289 (94%)
	(fragment).
A57293	latent transforming growth factor	10 . . . 1213	1056/1230 (85%)	0.0
	beta-binding protein 3 precursor -	6 . . . 1229	1078/1230 (86%)
	mouse, 1251 aa.
Q61810	LATENT TRANSFORMING	1 . . . 1213	1054/1240 (85%)	0.0
	GROWTH FACTOR-BETA	1 . . . 1231	1074/1240 (86%)
	BINDING PROTEIN - Mus
	musculus (Mouse), 1253 aa.
Q96HB9	SIMILAR TO LATENT	500 . . . 1218	719/743 (96%)	0.0
	TRANSFORMING GROWTH	4 . . . 746	719/743 (96%)
	FACTOR BETA BINDING
	PROTEIN 3 - Homo sapiens
	(Human), 746 aa (fragment).

[0490] PFam analysis predicts that the NOV35a protein contains the domains shown in the Table 35F.

TABLE 35F
Domain Analysis of NOV35a
		Identities/
	NOV35a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
EGF	99 . . . 126	14/47 (30%)	0.00034
		23/47 (49%)
TB	273 . . . 316	20/48 (42%)	0.013
		32/48 (67%)
EGF	345 . . . 380	16/47 (34%)	0.00073
		28/47 (60%)
TB	399 . . . 440	23/47 (49%)	3.5e−17
		35/47 (74%)
EGF	564 . . . 600	14/47 (30%)	0.0033
		28/47 (60%)
EGF	606 . . . 644	17/48 (35%)	0.66
		28/48 (58%)
EGF	716 . . . 745	12/47 (26%)	0.0073
		26/47 (55%)
EGF	751 . . . 786	16/47 (34%)	3e−07
		28/47 (60%)
EGF	792 . . . 826	14/47 (30%)	0.069
		26/47 (55%)
EGF	832 . . . 869	11/47 (23%)	8.6e−05
		26/47 (55%)
TB	889 . . . 932	21/47 (45%)	6.7e−14
		33/47 (70%)
EGF	959 . . . 996	14/47 (30%)	0.0034
		28/47 (60%)
EGF	1002 . . . 1037	15/47 (32%)	2.2e−05
		29/47 (62%)
TB	1061 . . . 1106	18/48 (38%)	0.0014
		33/48 (69%)
EGF	1173 . . . 1208	12/49 (24%)	0.32
		26/49 (53%)

Example 36

[0491] The NOV36 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 36A.

TABLE 36A
NOV36 Sequence Analysis
	SEQ ID NO: 111	1846 bp
NOV36a,	ATCATGCACTCCCAGAGACCTCCACTTGCACTCCTTGAGGGCTCCACCCTCGATAGAA
CG109844-01
DNA Sequence	AAGGAGAAATCGCAGCTTCACTCGTCTCTAGGCTGTGGAAAGTCTCCAATTCAACTCT
	GTTCCAAATGATGCTGGTCACTGTTTTGTTGGCTACCATTCTTGGTGACTGTGGTCCT
	CCACCTGAGTTACCATTTGCTTTTCCAATAAATCCGTTGTATGATACTGAATTCAAAA
	CTGGAACTACTCTGAAGTACACCTGCCACCCTGGGCATGGTAAAATCAATTCAAGTCG
	ACTGATTTGTGATGCCAAAGACTCGTGGAACTATAGTATCTTTTGTGCAAGTAAGCGA
	TGCAGAAATCCAGAATTAATCAATGGGATAGTGGAAGTTAAAAAAGATCTTCTCCTTG
	GTTCAACCATAAAATTCAGCTGCTCAGAGGGGTTTTTCTTAATTGGCTCAACCACCAG
	TCATTGTCAGATCCAAGGTAAAGGAGTTGATTGGAGTGATCCTCTCCCAGAAACCTCA
	GTTGCCAAGTGCGAGCCCCCTCCAGACATCAGGAATGGGAAGCACAGCGGTGGAGATC
	AAGAATTCTACACATATGCCTCCTCTGTCACCTACAGCTGCAACCCCTACTTCTCACT
	CATAGGCAACGTCTCCATCTCCTGCACCGTGGAGAATGAAACAATAGGTGTCTGGAGC
	CCAAACCCTCCTATCTGTGAAGAAATTGTCTGTCGTCGACCACAGATTCCAAAGGCAA
	TCTTTGTTTCTGGATTTGGACCCCTCTATACTTACAAAGACTCTATTATGGTTAACTG
	TGAGGAAGGTTATATCCTCAGAGGCAGCAGTTTAATCTATTGTGAAACGAATAATGAG
	TGGTATCCTTCTGTTCCCTCTTGCAGAGTGAATGGTTGCACTGTCCTACCGGACATTT
	CCTATGCTTCCTGGGAGAGAAATGACTACAACCTAAGTGATCACGAAATATTTGAAAT
	TGGAACTGAGTTGAAATATCTATGCAAACCTGGCTATAGACCTGTTTTAGATGAGCCT
	CTGACTGTGACTTGTCAGGAAAATTTCACATGGACATCTTCCAATGAGTGTGAGAGTG
	TATGTTGCCCAACACCAGATCTGGAGAATATCAGAATCATAAATGAAAGGAGGTATTT
	CACTGGTAGATGTGTCTATGCCTATGGAGACTATATTTCATATATGTGTGATGAAGGC
	TATTACCCTATTTCTGTTGACGGGGAGAGTTCCTGCCACACAGATGGCACATGGAAGC
	CTAAAATGCCAGCATGTGAGCCAGGTTGCAGTTTTGCCCCTAGTTTTGCCCATGGGCA
	TCCTAAACAAGTTAATTTATGCAACTGTTTCAAAAATGAGGCTGTATATAAATGTGAT
	GAAGGCTACACTGTGATCGGACAGGTGAAACTCACCTGCATTTCTTCCTGCTGGTCAT
	CTCCAGCCCCTCAATGTAAAAGTCTGTGTCTGAAACCAGAAATAGTGAATGGAAGGCT
	GTCTGTGGATAAGGATCAGTATGTTGAGTCTGAAAATGTTACCATTGAATGTGATTCT
	GGCTATGGTGTGGTTGGTCTCAAAAGTATCACTTGCTCAGAGAAGAGAACCTGGTACC
	CAGAAGTGCCCAGGTGTGAGTGGGAGGCACCTGAAGGTTGTGAGCAAGTGCTCACAGG
	CAGAAAACTCATGCAGTGTCTCCCAAGCCCAGAGGATGTGAAAGTGGCCCTGGAGGTG
	TATAAGCTGTCTCTGGAGATAAAACAACTTGAAAAAGAGAGAGACAAATTGATGAACA
	CCCATCAGAAATTTTCTGAAAAAGAGGAATGAAGGACTTATTTTTCCC
	ORF Start: ATG at 4	ORF Stop: TGA at 1828
	SEQ ID NO: 112	608 aa	MW at 68085.6kD
NOV36a	NHSQRPPLALLEGSTLDRKGEIAASLVSRLWKVSNSTLFQMMLVTVLLATILGDCGPP
CG109844-01
Protein Sequence	PELPFAFPINPLYDTEFKTGTTLKYTCHPGHGKINSSRLICDAKDSWNYSIFCASKRC
	RNPELINGIVEVKKDLLLGSTIKFSCSEGFFLIGSTTSHCQIQGKGVDWSDPLPETSV
	AKCEPPPDIRNGKHSGGDQEFYTYASSVTYSCNPYFSLIGNVSISCTVENETIGVWSP
	NPPICEEIVCRRPQIPKAIFVSGFGPLYTYKDSIMVNCEEGYILRGSSLIYCETNNEW
	YPSVPSCRVNGCTVLPDISYASWERNDYNLSDHEIFEIGTELKYLCKPGYRPVLDEPL
	TVTCQENLTWTSSNECESVCCPTPDLENIRIINERRYFTGRCVYAYGDYISYMCDEGY
	YPISVDGESSCHTDGTWKPKMPACEPGCSFAPSFAHGHPKQVNLCNCFKUEAVYKCDE
	GYTVIGQVKLTCISSCWSSPAPQCKSLCLKPEIVNGRLSVDKDQYVESENVTIECDSG
	YGVVGLKSITCSEKRTWYPEVPRCEWEAPEGCEQVLTGRKLMQCLPSPEDVKVALEVY
	KLSLEIKQLEKERDKLMNTHQKFSEKEE

[0492] Further analysis of the NOV36a protein yielded the following properties shown in Table 36B.

TABLE 36B
Protein Sequence Properties NOV36a
PSort   0.7900 probability located in plasma membrane;
analysis:
        0.3000 probability located in Golgi body; 0.2000 probability
        located in endoplasmic reticulum (membrane)
SignalP Cleavage site between residues 54 and 55
analysis:

[0493] A search of the NOV36a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 36C.

TABLE 36C
Geneseq Results for NOV36a
		NOV36a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAR13490	Human C4 binding protein - Homo	22 . . . 594	341/577 (59%)	0.0
	sapiens, 581 aa. [WO9111461-A,	1 . . . 570	428/577 (74%)
	08-AUG-1991]
AAW39924	Amino acid sequence of a mouse	30 . . . 602	315/575 (54%)	0.0
	sperm protein designated sp56 -	9 . . . 565	403/575 (69%)
	Mus sp, 579 aa. [WO9800440-A1,
	08-JAN-1998]
AAB43640	Human cancer associated protein	390 . . . 594	136/205 (66%)	3e−80
	sequence SEQ ID NO: 1085 -	10 . . . 209	162/205 (78%)
	Homo sapiens, 220 aa.
	[WO200055350-A1, 21-SEP-2000]
AAM50797	Human C3B/C4B receptor CR1	48 . . . 539	158/532 (29%)	2e−59
	(complement receptor type 1) -	1389 . . . 1897	238/532 (44%)
	Homo sapiens, 2039 aa.
	[US6316604-B1, 13-NOV-2001]
ABG00287	Novel human diagnostic protein	48 . . . 539	158/532 (29%)	2e−59
	#278 - Homo sapiens, 2039 aa.	1389 . . . 1897	238/532 (44%)
	[WO200175067-A2, 11-OCT-2001]

[0494] In a BLAST search of public sequence databases, the NOV36a protein was found to have homology to the proteins shown in the BLASTP data in Table 36D.

TABLE 36D
Public BLASTP Results for NOV36a
		NOV36a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched
Number	Protein/Organism/Length	Residues	Portion	Expect Value
P04003	C4b-binding protein alpha chain	1 . . . 594	347/598 (58%)	0.0
	precursor (C4bp) (Proline-rich	1 . . . 586	436/598 (72%)
	protein) (PRP) - Homo sapiens
	(Human), 597 aa.
S53711	C4BP alpha chain precursor -	1 . . . 595	330/599 (55%)	0.0
	rabbit, 597 aa.	1 . . . 587	414/599 (69%)
Q60736	SPERM FERTILIZATION	30 . . . 602	315/575 (54%)	0.0
	PROTEIN SP56 PRECURSOR -	9 . . . 565	403/575 (69%)
	Mus musculus (Mouse), 579 aa.
Q28065	C4b-binding protein alpha chain	1 . . . 595	327/601 (54%)	0.0
	precursor (C4bp) - Bos taurus	1 . . . 590	416/601 (68%)
	(Bovine), 610 aa.
Q63514	C4b-binding protein alpha chain	41 . . . 595	278/558 (49%)	e−174
	precursor (C4bp) - Rattus	1 . . . 550	385/558 (68%)
	norvegicus (Rat), 558 aa.

[0495] PFam analysis predicts that the NOV36a protein contains the domains shown in the Table 36E.

TABLE 36E
Domain Analysis of NOV36a
		Identities/
	NOV36a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
sushi	55 . . . 111	14/66 (21%)	7.2e−10
		41/66 (62%)
sushi	116 . . . 172	21/63 (33%)	2.2e−08
		41/63 (65%)
sushi	177 . . . 237	27/67 (40%)	9.2e−17
		49/67 (73%)
sushi	242 . . . 297	21/64 (33%)	6.6e−12
		40/64 (62%)
sushi	302 . . . 364	17/72 (24%)	9.9e−05
		46/72 (64%)
sushi	369 . . . 430	23/70 (33%)	4.1e−11
		46/70 (66%)
sushi	434 . . . 488	16/64 (25%)	2.3e−06
		35/64 (55%)
sushi	492 . . . 546	24/63 (38%)	3.7e−11
		37/63 (59%)

Example 37

[0496] The NOV37 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 37A.

TABLE 37A
NOV37 Sequence Analysis
	SEQ ID NO: 113	2974 bp
NOV37a,	CGGGGACTCGGAGGTACTGGGCGCGCGCGGCTCCGGCTCGGGACGCCTCGGGACGCCT
CG110014-02
DNA Sequence	CGGGGTCGGGTTCCGGTTGCGGCTGCTGCTGCGGCGCCCGCGCTTCCGTAGCGTTCCG
	CCTCCTGTGCCCGCCGCGGAGCAAGTCTGCGCGCCCGCCGTGCGCCCCTAAGCTCCTT
	TTACCTGAGCCCGCCGCGATGGGAGCTGCGCGGGGATCCCCGGCCAGACCCCGCCGGT
	TGCCTCTGCTCAGCGTCCTGCTGCTGCCGCTGCTGGGCGGTACCCAGACAGCCATTGT
	CTTCATCAAGCAGCCGTCCTCCCAGGATGCACTGCAGGGGCGCCGGGCGCTGCTTCGC
	TGTGAGGTTGAGGCTCCGGGCCCGGTACATGTGTACTGGCTGCTCGATGGGGCCCCTG
	TCCAGGACACGGAGCGGCGTTTCGCCCAGGGCAGCAGCCTGAGCTTTGCAGCTGTGGA
	CCCGCTGCAGGACTCTGGCACCTTCCAGTGTGTGGCTCGGGATGATGTCACTGGAGAA
	GAAGCCCGCAGTGCCAACGCCTCCTTCAACATCAAATGGATTGAGGCAGGTCCTGTGG
	TCCTGAAGCATCCAGCCTCGGAAGCTGAGATCCAGCCACAGACCCAGGTCAAACTTCG
	TTGCCACATTGATGGGCACCCTCGGCCCACCTACCAATGGTTCCGAGATGGGACCCCC
	CTTTCTGATGGTCAGAGCAACCACACAGTCAGCAGCAAGGAGCGGAACCTGACGCTCC
	GGCCAGCTGGTCCTGAGCATAGTGGGCTGTATTCCTGCTGCGCCCACAGTGCTTTTGG
	CCAGGCTTGCAGCAGCCAGAACTTCACCTTGAGCATTGCTGATGAAAGCTTTGCCAGG
	GTGGTGCTGGCACCCCAGGACGTGGTAGTAGCGAGGTATGAGGAGGCCATGTTCCATT
	GCCAGTTCTCAGCCCAGCCACCCCCGAGCCTGCAGTGGCTCTTTGAGGATGAGACTCC
	CATCACTAACCGCAGTCGCCCCCCACACCTCCGCAGAGCCACAGTGTTTGCCAACGGG
	TCTCTGCTGCTGACCCAGGTCCGGCCACGCAATGCAGGGATCTACCGCTGCATTGGCC
	AGGGGCAGAGGGGCCCACCCATCATCCTGGAAGCCACACTTCACCTAGCAGAGATTGA
	AGACATGCCGCTATTTGAGCCACGGGTGTTTACAGCTGGCAGCGAGGAGCGTGTGACC
	TGCCTTCCCCCCAAGGGTCTGCCAGAGCCCAGCGTGTGGTGGGAGCACGCGGGAGTCC
	GGCTGCCCACCCATGGCAGGGTCTACCAGAASGGCCACGAGCTGGTGTTGGCCAATAT
	TGCTGAAAGTGATGCTGGTGTCTACACCTGCCACGCGGCCAACCTGGCTGGTCAGCGG
	AGACAGGATGCCAACATCACTGTGGCCACTGTGCCCTCCTGGCTGAAGAAGCCCCAAG
	ACAGCCAGCTGGAGGAGGGCAAACCCGGCTACTTGGATTGCCTGACCCAGGCCACACC
	AAAACCTACAGTTGTCTGGTACAGAAACCAGATGCTCATCTCAGACGACTCACGGTTC
	GAGGTCTTCAAGAATGGGACCTTGCGCATCAACAGCGTGGAGGTGTATGATGGGACAT
	GGTACCGTTGTATGAGCAGCACCCCAGCCGGCAGCATCGAGGCGCAAGCCCGTGTCCA
	AGTGCTGGAAAAGCTCAAGTTCACACCACCACCCCAGCCACAGCAGTGCATGGAGTTT
	GACAAGGAGGCCACGGTGCCCTGTTCAGCCACAGGCCGAGAGAAGCCCACTATTAAGT
	GGGAACGGGCAGATGGGAGCAGCCTCCCAGAGTGGGTGACAGACAACGCTGGGACCCT
	GCATTTTGCCCGGGTGACTCGAGATGACGCTGGCAACTACACTTGCATTGCCTCCAAC
	GGGCCGCAGGGCCAGATTCGTGCCCATGTCCAGCTCACTGTGGCAGTTTTTATCACCT
	TCAAAGTGGAACCAGAGCGTACGACTGTGTACCCTTCCAAACTCTATCGGCTGATGCA
	GCGCTGCTGGGCCCTCAGCCCCAAGGACCGGCCCTCCTTCAGTGAGATTGCCAGCGCC
	CTGGGAGACAGCACCGTGGACAGCAAGCCGTGAGGAGGGAGCCCGCTCAGGATGGCCT
	GGGCAGGGGAGGACATCTCTAGAGGGAAGCTCACAGCATGATGGGCAAGATCCCTGTC
	CTCCTGGGCCCTGAGGCCCCTGCCCTAGTGCAACAGGCATTGCTGAGGTCTGAGCAGG
	GCCTGGCCTTTCCTCCTCTTCCTCACCCTCATCCTTTGGGAGGCTGACTTGGACCCAA
	ACTGGGCGACTAGGGCTTTGAGCTGGGCAGTTTTCCCTGCCACCTCTTCCTCTATCAG
	GGACAGTGTGGGTGCCACAGGTAACCCCAATTTCTGGCCTTCAACTTCTCCCCTTGAC
	CGGGTCCAACTCTGCCACTCATCTGCCAACTTTGCCTGGGGAGGGCTAGGCTTGGGAT
	GAGCTGGGTTTGTGGGGAGTTCCTTAATATTCTCAAGTTCTGGGCACACAGGGTTAAT
	GAGTCTCTTGGCCCACTGGTCCCACTTGGGGGTCTAGACCAGGATTATAGAGGACACA
	GCAAGTGAGTCCTCCCCACTCTGGGCTTGTGCACACTGACCCAGACCCACGGTCTTCC
	CCACCCTTCTCTCCTTTCCTCATCCTAAGTGCCTGGCAGATGAAGGAGTTTTCAGGAG
	CTTTTGACACTATATAAACCGCCCTTTTTGTATGCACCACGGGCGGCTTTTATATGTA
	ATTGCAGCGTGGGGTGGGTGGGCATGGGAGGTAGGGGTGGGCCCTGGAGATGAGGAGG
	GTGGGCCATCCTTACCCCACACTTTTATTGTTGTCGTTTTTTGTGTGTTTGTGTTTTT
	TTGTTTTTGTTTTTGTTTTTACACTCGCTGCTCTCAATAAATAAGCCTTTTTAAAAAA
	AAAAAAAAAAAAAAAA
	ORF Start: ATG at 193	ORF Stop: TGA at 2119
	SEQ ID NO: 114	642 aa	MW at 70935.5kD
NOV37a,	MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAP
CG110014-02
Protein Sequence	GPVHVYWLLDGAPVQDTERRFAQGSSLSFAAVDPLQDSGTFQCVARDDVTGEEARSAN
	ASFNIKWIEAGPVVLKHPASEAEIQPQTQVKLRCHIDGHPRPTYQWFRDGTPLSDGQS
	NHTVSSKKRNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQ
	DVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQ
	VRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKG
	LPEPSVWWEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDANI
	TVATVPSWLKKPQDSQLEEGKPGYLDCLTQATPKPTVVWYRNQMLISEDSRFEVFKNG
	TLRINSVEVYDGTWYRCMSSTPAGSIEAQARVQVLEKLKFTPPPQPQQCMEFDKEATV
	PCSATGREKPTIKWERADGSSLPEWVTDNAGTLHFARVTRDDAGNYTCIASNGPQGQI
	RAHVQLTVAVFITFKVEPERTTVYPSKLYRLMQRCWALSPKDRPSFSEIASALGDSTV
	RAHVQLTVAVFITFKVEPERTTVYPSKLYRLMQRCWALSPKDRPSFSEIASALGDSTV
	DSKP
	SEQ ID NO: 115	3693 bp
NOV37b,	CTTTTCCTGAGCCCGCCGCGATGGGAGCTGCGCGGGGATCCCCGGCCAGACCCCGCCG
CG110014-03
DNA Sequence	GTTGCCTCTGCTCAGCGTCCTGCTGCTGCCGCTGCTGGGCGGTACCCAGACAGCCATT
	GTCTTCATCAAGCAGCCGTCCTCCCAGGATGCACTGCAGGGGCGCCGGGCGCTGCTTC
	GCTGTGAGGTTGAGGCTCCGGGCCCGGTACATGTGTACTGGCTGCTCGATGGGGCCCC
	TGTCCAGGACACGGAGCGGCGTTTCGCCCAGGGCAGCAGCCTGAGCTTTGCAGCTGTG
	GACCGGCTGCAGGACTCTGGCACCTTCCAGTGTGTGGCTCGGGATGATGTCACTGGAG
	AAGAAGCCCGCAGTGCCAACGCCTCCTTCAACATCAAATGGATTGAGGCAGGTCCTGT
	GGTCCTGAAGCATCCAGCCTCGGAAGCTGAGATCCAGCCACAGACCCAGGTCACACTT
	CGTTGCCACATTGATGGGCACCCTCGATGAAAGCTTTGCCAGGGTGGTGCTGGCACCC
	CAGGACGTGGTAGTAGCGAGGTATGAGGAGGCCATGTTCCATTGCCAGTTCTCAGCCC
	AGCCACCCCCGAGCCTGCAGTGGCTCTTTGAGGATGAGACTCCCATCACTAACCGCAG
	TCGCCCCCCACACCTCCGCAGAGCCACAGTGTTTGCCAACGGGTCTCTGCTGCTGACC
	CAGGTCCGGCCACGCAATGCAGGGATCTACCGCTGCATTGGCCAGGGGCAGAGGGGCC
	CACCCATCATCCTGGAAGCCACACTTCACCTAGCAGAGATTGAAGACATGCCGCTATT
	TGAGCCACGGGTGTTTACAGCTGGCAGCGAGGAGCGTGTGACCTGCCTTCCCCCCAAG
	GGTCTGCCAGAGCCCAGCGTGTGGTGGGAGCACGCGGGAGTCCGGCTGCCCACCCATG
	GCAGGGTCTACCAGAAGGGCCACGAGCTGGTGTTGGCCATJATTGCTGAAAGTGATGC
	TGGTGTCTACACCTGCCACGCGGCCAACCTGGCTGGTCAGCGGAGACAGGATGTCAAC
	ATCACTGTGGCCACTGTGCCCTCCTGGCTGAAGAAGCCCCAAGACAGCCAGCTGGAGG
	AGGGCAAACCCGGCTACTTGGATTGCCTGACCCAGGCCACACCAAAACCTACAGTTGT
	CTGGTACAGAAACCAGATGCTCATCTCAGAGGACTCACGGTTCGAGGTCTTCAAGAAT
	GGGACCTTGCGCATCAACAGCGTGGAGGTGTATGATGGGACATGGTACCGTTGTATGA
	GCAGCACCCCAGCCGGCAGCATCGAGGCGCAAGCCCGTGTCCAAGTGCTGGAAAAGCT
	CAAGTTCACACCACCACCCCAGCCACAGCAGTGCATGGAGTTTGACAAGGAGGCCACG
	GTGCCCTGTTCAGCCACAGGCCGAGAGAAGCCCACTATTAAGTGGGAACGGGCAGATG
	GGAGCAGCCTCCCAGAGTGGGTGACAGACAACGCTGGGACCCTGCATTTTGCCCGGGT
	GACTCGAGATGACGCTGGCAACTACACTTGCATTGCCTCCAACGGGCCGCAGGGCCAG
	ATTCGTGCCCATGTCCAGCTCACTGTGGCAGTTTTTATCACCTTCAAAGTGGAACCAG
	AGCGTACGACTGTGTACCAGGGCCACACAGCCCTACTGCAGTGCGAGGCCCAGGGAGA
	CCCCAAGCCGCTGATTCAGTGGAAAGGCAAGGACCGCATCCTGGACCCCACCAAGCTG
	GGACCCAGGATGCACATCTTCCAGAATGGCTCCCTGGTGATCCATGACGTGGCCCCTG
	AGGACTCAGGCCGCTACACCTGCATTGCAGGCAACAGCTGCAACATCAAGCACACGGA
	GGCCCCCCTCTATGTCGTGGACAAGCCTGTGCCGGAGGAGTCGGAGCGCCCTGGCAGC
	CCTCCCCCCTACAAGATGATCCAGACCATTGGGTTGTCGGTGGGTGCCGCTGTGGCCT
	ACATCATTGCCGTGCTGGGCCTCATGTTCTACTGCAAGAAGCGCTGCAAAGCCAAGCG
	GCTGCAGAAGCAGCCCGAGGGCGAGGAGCCAGAGATGGAATGCCTCAACGGTGGGCCT
	TTGCAGAACGGGCAGCCCTCAGCAGAGATCCAAGAAGAAGTGGCCTTGACCAGCTTGG
	GCTCCGGCCCCGCGGCCCCCAACAAACGCCACAGCACAAGTGATAAGATGCACTTCCC
	ACGGTCTAGCCTGCAGCCCATCACCACGCTGGGGAAGAGTGAGTTTGGGGAGGTGTTC
	CTGGCAAAGGCTCAGGGCTTGGAGGAGGGAGTGGCAGAGACCCTGGTACTTGTGAAGA
	GCCTGCAGAGCAAGGATGAGCAGCAGCAGCTGGACTTCCGGAGGGAGTTGGAGATGTT
	TGGGAAGCTGAACCACGCCAACGTGGTGCGGCTCCTGGGGCTGTGCCGGGAGGCTGAG
	CCCCACTACATGGTGCTGGAATATGTGGATCTGGGAGACCTCAAGCAGTTCCTGAGGA
	TTTCCAAGAGCAAGGATGAAAAATTGAAGTCACGGCCCCTCAGCACCAAGCAGAAGGT
	GGCCCTATGCACCCAGGTAGCCCTGGGCATGGAGCACCTGTCCAACAACCGCTTTGTG
	CATAAGGACTTGGCTGCGCGTAACTGCCTGGTCAGTGCCCAGAGACAAGTGAAGGTGT
	CTGCCCTGGGCCTCAGCAAGGATGTGTACAACAGTGAGTACTACCACTTCCGCCAGGC
	CTGGGTGCCGCTGCGCTGGATGTCCCCCGAGGCCATCCTGGAGGGTGACTTCTCTACC
	AAGTCTGATGTCTGGGCCTTCGGTGTGCTGATGTGGGAAGTGTTTACACATGGAGAGA
	TCCCCCATGGTGGGCAGGCAGATGATGAAGTACTGGCAGATTTGCAGGCTGGGAAGGC
	TAGACTTCCTCAGCCCGAGGGCTGCCCTTCCAAACTCTATCGGCTGATGCAGCGCTGC
	TGGGCCCTCAGCCCCAAGGACCGGCCCTCCTTCAGTGAGATTGCCAGCGCCCTGGGAG
	ACAGCACCGTGGACAGCAAGCCGTGAGGAGGGAGCCCGCTCAGGATGGCCTGGGCAGG
	GGAGGACATCTCTAGAGGGAAGCTCACAGCATGATGGGCAAGATCCCTGTCCTCCTGG
	GCCCTGAGGCCCCTGCCCTAGTGCAACAGGCATTGCTGAGGTCTGAGCAGGGCCTGGC
	CTTTCCTCCTCTTCCTCACCCTCATCCTTTGGGAGGCTGACTTGGACCCAAACTGGGC
	GACTAGGGCTTTGAGCTGGGCAGTTTTCCCTGCCACCTCTTCCTCTATCAGGGACAGT
	GTGGGTGCCACAGGTAACCCCAATTTCTGGCCTTCAACTTCTCCCCTTGACCGGGTCC
	AACTCTGCCACTCATCTGCCAACTTTGCCTGGGGAGGGCTAGGCTTGGGATGAGCTGG
	GTTTGTGGGGAGTTCCTTAATATTCTCAAGTTCTGGGCACACAGGGTTAATGAGTCTC
	TTGGCCCACTGGTCCCACTTGGGGGTCTAGACCAGGATTATAGAGGACACAGCAAGTG
	AGTCCTCCCCACTCTGGGCTTGTGCACACTGACCCAGACCCACGTCTTCCCCACCCTT
	CTCTCCTTTCCTCATCCTAAGTGCCTGGCAGATGAAGGAGTTTTCAGGAGCTTTTGAC
	ACTATATAAACCGCCCTTTTCGTATGCACCACGGGCGGC
	ORF Start: ATG at 478	ORF Stop: TGA at 3040
	SEQ ID NO: 116	854 aa	MW at 95008.5kD
NOV37b,	MGTLDESFARVVLAPQDVVVARYEEANFHCQFSAQPPPSLQWLFEDETPITNRSRPPH
CG110014-03
Protein Sequence	LRRATVFANGSLLLTQVRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRV
	FTAGSEERVTCLPPKGLPEPSVWWEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYT
	CHAANLAGQRRQDVNITVATVPSWLKKPQDSQLEEGKPGYLDCLTQATPKPTVVWYRN
	QMLISEDSRFEVFKNGTLRINSVEVYDGTWYRCMSSTPAGSIEAQARVQVLEKLKFTP
	PPQPQQCMEFDKEAIVPCSATGREKPTIKWERADGSSLPEWVTDNAGTLHFARVTRDD
	AGNYTCIASNGPQGQIRAHVQLTVAVFITFKVEPERTTVYQGHTALLQCEAQGDPKPL
	IQWKGKDRILDPTKLGPRMHIFQNGSLVIHDVAPEDSGRYTCIAGNSCNIKHTEAPLY
	VVDKPVPEESEGPGSPPPYKMIQTIGLSVGAATAYIIAVLGLMFYCKKRCKAKRLQKQ
	PEGEEPEMECLNGGPLQNGQPSAEIQEEVALTSLGSGPAAPNKRHSTSDKMHFPRSSL
	QPITTLGKSEFGEVFLAKAQGLEEGVAETLVLVKSLQSKDEQQQLDFRRELEMFGKLN
	HANVVRLLGLCREAEPHYMVLEYVDLGDLKQFLRISKSKDEKLKSRPLSTKQKVALCT
	QVALGMEHLSNNRFVHKDLAARNCLVSAQRQVKVSALGLSKDVYNSEYYHFRQAWVPL
	RWMSPEAILEGDFSTKSDVWAFGVLMWEVFTHGEMPHGGQADDEVLADLQAGKARLPQ
	PEGCPSKLYRLMQRCWALSPKDRPSFSEIASALGDSTVDSKP
	SEQ ID NO: 117	2866 bp
NOV37c,	CTCAGCTCCTTTTCCTGAGCCCGCCGCGATGGGAGCTGCGCGGGGATCCCCGGCCAGA
CG110014-04
DNA Sequence	CCCCGCCGGTTGCCTCTGCTCAGCGTCCTGCTGCTGCCGCTGCTGGGCGGTACCCAGA
	CAGCCATTGTCTTCATCAAGCAGCCGTCCTCCCAGGATGCACTGCAGGGGCGCCGGGC
	GCTGCTTCGCTGTGAGGTTGAGGCTCCGGGCCCGGTACATGTGTACTGGCTGCTCGAT
	GGGGCCCCTGTCCAGGACACGGAGCGGCGTTTCGCCCAGGGCAGCAGCCTGAGCTTTG
	CAGCTGTGGACCGGCTGCAGGACTCTGGCACCTTCCAGTGTGTGGCTCGGGATGATGT
	CACTGGAGAAGAAGCCCGCAGTGCCAACGCCTCCTTCAACATCAAATGGATTGAGGCA
	GGTCCTGTGGTCCTGAAGCATCCAGCCTCGGAAGCTGAGATCCAGCCACAGACCCAGG
	TCACACTTCGTTGCCACATTGATGGGCACCCTCGGCCCACCTACCAATGGTTCCGAGA
	TGGGACCCCCCTTTCTGATGGTCAGAGCAACCACACAGTCAGCAGCAAGGAGCGGAAC
	CTGACGCTCCGGCCAGCTGGTCCTGAGCATAGTGGGCTGTATTCCTGCTGCGCCCACA
	GTGCTTTTGGCCAGGCTTGCAGCAGCCAGAACTTCACCTTGAGCATTGCTGATGAAAG
	CTTTGCCAGGGTGGTGCTGGCACCCCAGGACGTGGTAGTAGCGAGGTATGAGGAGGCC
	ATGTTCCATTGCCAGTTCTCAGCCCAGCCACCCCCGAGCCTGCAGTGGCTCTTTGAGG
	ATGAGACTCCCATCACTAACCGCAGTCGCCCCCCACACCTCCGCAGAGCCACAGTGTT
	TGCCAACGGGTCTCTGCTGCTGACCCAGGTCCGGCCACGCAATGCAGGGATCTACCGC
	TGCATTGGCCAGGGGCAGAGGGGCCCACCCATCATCCTGGAAGCCACACTTCACCTAG
	CAGAGATTGAAGACATGCCGCTATTTGAGCCACGGGTGTTTACAGCTGGCAGCGAGGA
	GCGTGTGACCTGCCTTCCCCCCAAGGGTCTGCCAGAGCCCAGCGTGTGGTGGGAGCAC
	GCGGGAGTCCGGCTGCCCACCCATGGCAGGGTCTACCAGAAGGGCCACGAGCTGGTGT
	TGGCCAATATTGCTGAAAGTGATGCTGGTGTCTACACCTGCCACGCGGCCAACCTGGC
	TGGTCAGCGGAGACAGGATGTCAACATCACTGTGGCCACTGTGCCCTCCTGGCTGAAG
	AAGCCCCAAGACAGCCAGCTGGAGGAGGGCAAACCCGGCTACTTGGATTGCCTGACCC
	AGGCCACACCAAAACCTACAGTTGTCTGGTACAGAAACCAGATGCTCATCTCAGAGGA
	CTCACGGTTCGAGGTGTTCCTGGCAAAGGCTCAGGGCTTGGAGGAGGGAGTGGCAGAG
	ACCCTGGTACTTGTGAAGAGCCTGCAGAGCAAGGATGAGCAGCAGCAGCTGGACTTCC
	GGAGGGAGTTGGAGATGTTTGGGAAGCTGAACCACGCCAACGTGGTGCGGCTCCTGGG
	GCTGTGCCGGGAGGCTGAGCCCCACTACATGGTGCTGGAATATGTGGATCTGGGAGAC
	CTCAAGCAGTTCCTGAGGATTTCCAAGAGCAAGGATGAAAAATTGAAGTCACAGCCCC
	TCAGCACCAAGCAGAAGGTGGCCCTATGCACCCAGGTAGCCCTGGGCATGGAGCACCT
	GTCCAACAACCGCTTTGTGCATAAGGACTTGGCTGCGCGTAACTGCCTGGTCAGTGCC
	CAGAGACAAGTGAAGGTGTCTGCCCTGGGCCTCAGCAAGGATGTGTACAACAGTGAGT
	ACTACCACTTCCGCCAGGCCTGGGTGCCGCTGCGCTGGATGTCCCCCGAGGCCATCCT
	GGAGGGTGACTTCTCTACCAAGTCTGATGTCTGGGCCTTCGGTGTGCTGATGTGGGAA
	GTGTTTACACATGGAGAGATGCCCCATGGTGGGCAGGCAGATGATGAAGTACTGGCAG
	ATTTGCAGGCTGGGAAGGCTAGACTTCCTCAGCCCGAGGGCTGCCCTTCCAAACTCTA
	TCGGCTGATGCAGCGCTGCTGGGCCCTCAGCCCCAAGGACCGGCCCTCCTTCAGTGAG
	ATTGCCAGCGCCCTGGGAGACAGCACCGTGGACAGCAAGCCGTGAGGAGGGAGCCCGC
	TCAGGATGGCCTGGGCAGGGGAGGACATCTCTAGAGGGAAGCTCACAGCATGATGGGC
	AAGATCCCTGTCCTCCTGGGCCCTGAGGCCCCTGCCCTAGTGCAACAGGCATTGCTGA
	GGTCTGAGCAGGGCCTGGCCTTTCCTCCTCTTCCTCACCCTCATCCTTTGGGAGGCTG
	ACTTGGACCCAAACTGGGCGACTAGGGCTTTGAGCTGGGCAGTTTTCCCTGCCACCTC
	TTCCTCTATCAGGGACAGTGTGGGTGCCACAGGTAACCCCAATTTCTGGCCTTCAACT
	TCTCCCCTTGACCGGGTCCAACTCTGCCACTCATCTGCCAACTTTGCCTGGGGAGGGC
	TAGGCTTGGGATGAGCTGGGTTTGTGGGGAGTTCCTTAATATTCTCAAGTTCTGGGCA
	CACAGGGTTAATGAGTCTCTTGGCCCACTGGTCCCACTTGGGGGTCTAGACCAGGATT
	ATAGAGGACACAGCAAGTGAGTCCTCCCCACTCTGCGCTTGTGCACACTGACCCAGAC
	CCACGTCTTCCCCACCCTTCTCTCCTTTCCTCATCCTAAGTGCCTGGCAGATGAAGGA
	GTTTTCAGGAGCTTTTGACACTATATAAACCGCCCTTTTTGTATGCACCACGGGCGGC
	TTTTATATGTAATTGCAGCGTGGG
	ORF Start: ATG at 29	ORF Stop: TGA at 2189
	SEQ ID NO: 118	720 aa	MW at 80086.2kD
NOV37c,	MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAP
CG110014-04
Protein Sequence	GPVHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSAN
	ASFNIKWIEAGPVVLKHPASEAEIQPQTQVThRCHIDGHPRPTYQWFRDGTPLSDGQS
	NHTVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQ
	DVVVARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQ
	VRPRNAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKG
	LPEPSVWWEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNI
	TVATVPSWLKKPQDSQLEEGKPGYLDCLTQATPKPTVVWYRNQMLISEDSRFEVFLAK
	AQGLEEGVAETLVLVKSLQSKDEQQQLDFRRELEMFGKLNHANVVRLLGLCREAEPHY
	MVLEYVDLGDLKQFLRISKSKDEKLKSQPLSTKQKVALCTQVALGMEHLSNNRFVHKD
	LAARNCLVSAQRQVKVSALGLSKDVYNSEYYHFRQAWVPLRWMSPEAILEGDFSTKSD
	VWAFGVLMWEVFTHGEMPHGGQADDEVLADLQAGKARLPQPEGCPSKLYRLMQRCWAL
	SPKDRPSFSEIASALGDSTVDSKP

[0497] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 37B.

TABLE 37B
Comparison of NOV37a against NOV37b and NOV37c.
	NOV37a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV37b	221 . . . 604	383/384 (99%)
	5 . . . 388	383/384 (99%)
NOV37c	28 . . . 461	431/434 (99%)
	28 . . . 461	431/434 (99%)

[0498] Further analysis of the NOV37a protein yielded the following properties shown in Table 37C.

TABLE 37C
Protein Sequence Properties NOV37a
PSort     0.6950 probability located in outside; 0.1900 probability
analysis: located in lysosome (lumen); 0.1900 probability
          located in plasma membrane; 0.1363 probability
          located in microbody (peroxisome)
SignalP   Cleavage site between residues 31 and 32
analysis:

[0499] A search of the NOV37a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 37D.

TABLE 37D
Geneseq Results for NOV37a
		NOV37a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAW08747	Human colon carcinoma kinase 4	1 . . . 604	599/604 (99%)	0.0
	(CCK-4) - Homo sapiens, 1070 aa.	1 . . . 604	600/604 (99%)
	[WO9637610-A2, 28-NOV-1996]
ABB68257	Drosophila melanogaster	128 . . . 588	136/486 (27%)	5e−40
	polypeptide SEQ ID NO: 31563 -	56 . . . 531	217/486 (43%)
	Drosophila melanogaster, 1395 aa.
	[WO200171042-A2, 27-SEP-2001]
AAY08404	Human ROBO1 protein - Homo	128 . . . 602	144/508 (28%)	1e−39
	sapiens, 1649 aa. [WO9920764-A1,	68 . . . 555	216/508 (42%)
	29-APR-1999]
AAY13566	Human Robo 1 polypeptde - Homo	128 . . . 602	144/508 (28%)	1e−39
	sapiens, 1651 aa. [WO9925833-A1,	68 . . . 555	216/508 (42%)
	27-MAY-1999]
AAY08401	Drosophila sp. ROBO1 protein -	128 . . . 588	135/486 (27%)	2e−39
	Drosophila sp, 1395 aa.	56 . . . 531	217/486 (43%)
	[WO9920764-A1, 29-APR-1999]

[0500] In a BLAST search of public sequence databases, the NOV37a protein was found to have homology to the proteins shown in the BLASTP data in Table 37E.

TABLE 37E
Public BLASTP Results for NOV37a
		NOV37a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
JC4593	protein-tyrosine kinase-related	1 . . . 604	601/604 (99%)	0.0
	receptor PTK7 precursor - human,	1 . . . 604	601/604 (99%)
	1070 aa.
AAC50484	TRANSMEMBRANE	1 . . . 604	601/604 (99%)	0.0
	RECEPTOR PRECURSOR -	1 . . . 604	601/604 (99%)
	Homo sapiens (Human), 1070 aa.
Q13308	Tyrosine-protein kinase-like 7	1 . . . 604	599/604 (99%)	0.0
	precursor (Colon carcinoma kinase-	1 . . . 604	600/604 (99%)
	4) (CCK-4) - Homo sapiens
	(Human), 1070 aa.
Q91048	Tyrosine-protein kinase-like 7	17 . . . 604	382/589 (64%)	0.0
	precursor (Kinase like protein) -	4 . . . 585	462/589 (77%)
	Gallus gallus (Chicken), 1051 aa.
Q9NSQ6	HYPOTHETICAL 40.9 KDA	357 . . . 461	104/105 (99%)	5e−56
	PROTEIN - Homo sapiens	1 . . . 105	104/105 (99%)
	(Human), 364 aa (fragment).

[0501] PFam analysis predicts that the NOV37a protein contains the domains shown in the Table 37F.

TABLE 37F
Domain Analysis of NOV37a
		Identities/
	NOV37a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
ig	46 . . . 103	17/60 (28%)	9.7e−07
		42/60 (70%)
ig	143 . . . 202	17/63 (27%)	1.4e−09
		48/63 (76%)
ig	239 . . . 303	14/68 (21%)	0.00022
		47/68 (69%)
ig	336 . . . 393	15/60 (25%)	3e−05
		38/60 (63%)
ig	426 . . . 483	16/61 (26%)	0.019
		37/61 (61%)
ig	517 . . . 572	15/59 (25%)	3.1e−09
		41/59 (69%)
pkinase	605 . . . 629	8/28 (29%)	0.024
		20/28 (71%)

Example 38

[0502] The NOV38 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 38A.

TABLE 38A
NOV38 Sequence Analysis
	SEQ ID NO: 119	2894 bp
NOV38a,	GATGGTGGGCTGTGGGGTGGCAGTTTTATGTTTGTGGGTTTCCTGCGGCGCTGCAGCG
CG110187-01
DNA Sequence	GGACAGCTCGAGTACTCAGTGCCGGAGGAGACGGAGCGGGGCGTAGCCGTAGGCAATC
	TCTCCGCGGACTTGAGGCTGCCAGCGGCCGCTATGTCCTCGCGGAACTTTCGCTTCCT
	TTCCAGCCACCGCGAGCTCTACTTCGGGGTGGATCTACCCAGCGGCAATTTGGTGGTC
	AGAGAGCCGGCGGACCGCGAACAGCTGTGCAGGGCCAAAGCTGCCTGCGTCTTGACCT
	ACGACCTGGTGCTCGAGGACCCGCTGGAGCTGCACAAGATTCGGATTCACGTCCTGGA
	CACCAATGACAACTCACCTCTCTTTCCTGCCGGCGACGTGCAGCTGCACATCCCCGAG
	TTCCTGACGCCCGGAGCCCGCTTTACTCTCCCGAATGCCCAAGATGACGACGAGGGAA
	GCAATGGGATACTAAGCTACAGCCTAAGCCCCAGTCAGCACTTTCGCCTGGACATGGG
	ATCGCGGGTTGACGGCAGCGAATACCCGGAGTTGGTGTTGGAGAAAGCACTGGATCGC
	GAACAGCGCGCCACCCACCTGCTGGTGCTTACAGCTCGGGACGGCGGGCTACCTGCCC
	GCTCAGGAGACGCACAAGTCACCATCATTGTGGTGGACACAAATGACAACGCGCCTGT
	ATTTGAGCGCTCCGTATACCGCACCAAGGTTCCAGAGACTGCACCCAATGGGACTGTG
	TTATTCCGAGTTCAAGCCTTGGATCCAGATGAAGGGTCCAATGGGGAAGTCCAATACT
	CCCTAAGCAACAGCACGCAAGCAGAGCTGCGACACCGCTTTCACGTTCACCCTAAAAG
	TGGGGAGGTGCAAGTAGCTGCTTCACTAGGTCCGCCTGAAACGCTCTTGGAGGCATAC
	ATTGAGGCGAGGGACGAAGGTGTCTTTGGTTTAGCTAGCACCGCTAAACTGCTGGTGG
	AGGTGACTGACGTGAACGATCATGCCCCCGAACTGGACTTCCTGACTCTTTCGAACCC
	AGTACCTGAGGACGCTGCCCCTGGCACAGTGATTGCTCTCTTTAGTGTAAAGGATGAA
	GACCTCGATTCTAATGGTAGGGTCATTTGTGGCATGTCTAGTGCAGGCCCTTTTCAGC
	TGACGGCTTCCTTTGACAACTACTACAGCCTGCTGATTGATGGGCCCCTGGACCGGGA
	GCAGATCAGTGAATACCAAGTCCTGATCACGGCCTCAGATAGTGGCTCACCCCCACTT
	AGCACCCGAAGGACAATCACTGTGTCAGTTGCTGATGTGAATGACAATACACCAAACT
	TTCCTCAACCCCAGCAGGAACTTTTCGTTGCTGAAAACAATGGCCCTGGGGCCTCTCT
	AGGCCGAGTGTTTGCCCAGGACCCCGACCTGGGGAAGAATGGCCTTGTCTCTTATGAG
	CTGTTGGATGTTATCTCTGAACGGCCATCAGCCTCTAGCTTGGTGGCAGTGGAATCAG
	CCAGTGGGGCCATCACTGCCAAAACTTCCTTTGACTTTGAGCAGCTCAGGGGGTTTCA
	TTTCCAAGTAGAGGGCCGGGATGGTGGCATTCCTCCCAGAAGTGCAACAGTGACTATA
	AACTTGTTTGTGGTAGATAGGAATGACAATTATCCGGTTATCTTCGTTCCCTTGCCCA
	GAAATGGTTCTGTCCCAGTGGAAATTGTGCCCCGCTCTGCCAGGACTGGACACTTGGT
	CACAAAAGTGGTAGCAGAGGATGCTGACAGTGGTTCTAATGCCTGGCTTTCCTACCAC
	ATCTCCCGGGCGTCTGACTCTAGTCTCTTTAGAATTTCAGCCAATATAGGTGAGCTCC
	GTACTGCTCGCTTAGTTCTTCCCACTGATGCAGTTAAGCAGAGGGTGGTGGTAGTGGT
	TCGGGACCATGGAGACCCACCACTTTCCTCCTCTGTCACTCTGGGTGTGCTGTTGAGC
	AACTCTGTCCCTCAGTTACTTCCAGACTTTGAAGATGTCTGGGAACCAGGAGGGCAGC
	TTTCTGCCCAGAACTTGTATTTAGTAATTGCCTTGGCTTGTATTTCCTTTTTATTTCT
	GGGGTGCTTACTTTTCTTCGTGTGTACCAAGTTGCACCAGAGCCCAGGCTGTTGCGCT
	CAGAGCTGCTGTCGCTCTACAGAGGATCTGAGGTATGGAAGTAAGATGGTTTCAAATC
	CTTGCATGACATCAGCCACCATAGATGTCACTACAGTTGAGAGACTTTCTCAGACTTA
	TCTCTATCGGGCCTCTCTGGGACTTGGTTCTGATAATAACAGTTTGCTGTTGCGTGGG
	GAGTACAATGCTGCCGACCTGCGAAATCTTGCCACTGGGGTAGGACTGAATTTGCCAA
	TATCCTGTATTCAGATTCGGAATAGGAAAGGGGATCACGCTAATGTCAATGCCATGCC
	ACGACAGCCCAACCCTGACTGGCGTTACTCTGCCTCCCTGAGAGCAGGCATGCACAGC
	TCTGTGCACCTAGAGGAGGCTGGCATTCTACGGGCTGGTCCAGGAGGGCCTGATCAGC
	AGTGGCCAACAGTATCCAGTGCAACACCAGAACCAGAGGCAGGAGAAGTGTCCCCTCC
	AGTCGGTGCGGGTGTCAACAGCAACAGCTGGACCTTTAAATACGGACCAGGCAACCCC
	AAACAATCCGGTCCCGGTGAGTTGCCCGACAAATTCATTATCCCAGGATCTCCTGCAA
	TCATCTCCATCCGGCAGGAGCCTACTAACAGCCAAATTGACAAAAGTGACTTCATAAC
	CTTCGGCAAAAAGGAGGAGACCAAGAAAAAGAAGAAAAAGAAGAAGGGTAACAAGACC
	CAGGAGAAAAAAGAGAAAGGGAACAGCACGACTGACAACGTGACCAGTGAG
	ORF Start: ATG at 2	ORF Stop: TGA at 2891
	SEQ ID NO: 120	963 aa	MW at 103961.5kD
NOV38a,	MVGCGVAVLCLWVSCGAAAGQLEYSVPEETERGVAVGNLSADLRLPAAAMSSRNFRFL
CG110187-01
Protein Sequence	SSHRELYFGVDLPSGNLVVREPADREQLCPAKAACVLTYDLVLEDPLELHKIRIHVLD
	TNDNSPLFPAGDVQLHIPEFLTPGARFTLFNAQDDDEGSNGILSYSLSPSQHFRLDMG
	SRVDGSEYPELVLEKALDREQRATHLLVLTARDGGLPARSGDAQVTIIVVDTNDNAPV
	FERSVYRTKVPETAPNGTVLFRVQALDPDEGSNGEVQYSLSNSTQAELRHRFHVHPKS
	GEVQVAASLGPPETLLEAYIEARDEGVFGLASTAKLLVEVTDVNDHAPELDFLTLSNP
	VPEDAAPGTVIALFSVKDEDLDSNGRVICGMSSAGPFQLTASFDNYYSLLIDGPLDRE
	QISEYQVLITASDSGSPPLSTRRTITVSVADVNDNTPNFPQPQQELFVAENNGPGASL
	GRVFAQDPDLGKNGLVSYELLDVISERPSASSLVAVESASGAITAKTSFDFEQLRGFH
	FQVEGRDGGIPPRSATVTINLFVVDRNDNYPVILVPLPRNGSVPVEIVPRSARTGHLV
	TKVVAEDADSGSNAWLSYHISRASDSSLFRISANIGELRTARLVLPTDAVKQRVVVVV
	RDHGDPPLSSSVTLGVLLSNSVPQLLPDFEDVWEPGGQLSAQNLYLVIALACISFLFL
	GCLLFFVCTKLHQSPGCCAQSCCRSTEDLRYGSKMVSNPCMTSATIDVTTVERLSQTY
	LYRASLGLGSDNNSLLLRGEYNAADLRNLATGVGLNLPISCIQIRNRKGDHANVNAMP
	RQPNPDWRYSASLRAGMHSSVHLEEAGILRAGPGGFDQQWPTVSSATPEPEAGEVSFP
	VGAGVNSNSWTFKYGPGNPKQSGPGELPDKFIIPGSPAIISIRQEPTNSQIDKSDFIT
	FGKKEETKKKKKKKKGNKTQEKKEKGNSTTDNSDQ
	SEQ ID NO: 121	2010 bp
Nov38b,	AGATCTGCGGGACAGCTCGAGTACTCAGTGCGGGAGGAGACGGAGCGGGGCGTAGCCG
CG110187-03
DNA Sequence	TAGGCAATCTCTCCGCGGACTTGAGGCTGCCAGCGGCCGCTATGTCCTCGCGGAACTT
	TCGCTTCCTTTCCAGCCACCGCGAGCTCTACTTCGGGGTGGATCTACCCAGCGGCAAT
	TTGGTGGTCAGAGAGCCGGCGGACCGCGAACAGCTGTGCAGGGCCAAAGCTGCCTGCG
	TCTTGACCTACGACCTGGTGCTCGAGGACCCGCTGGAGCTGCACAAGATTCGGATTCA
	CGTCCTGGACACCAATGACAACTCACCTCTCTTTCCTGCCGGCGACGTGCAGCTGCAC
	ATCCCCGAGTTCCTGACGCCCGGAGCCCGCTTTACTCTCCCGAATGCCCAZGATGACG
	ACGAGGGAAGCAATGGGATACTAAGCTACAGCCTAAGCCCCAGTCAGCACTTTCGCCT
	GGACATGGGATCGCGGGTTGACGGCAGCGAATACCCGGAGTTGGTGTTGGAGAAAGCA
	CTGGATCGCGAACAGCGCGCCACCCACCTGCTGGTGCTTACAGCTCGGGACGGCGGGC
	TACCTGCCCGCTCAGGAGACGCACAAGTCACCATCATTGTGGTGGACACAAATGACAA
	CGCGCCTGTATTTGAGCGCTCCGTATACCGCACCAAGGTTCCAGAGACTGCACCCAAT
	GGGACTGTGTTATTCCGAGTTCAAGCCTTGGATCCAGATGAAGGGTCCAATGGGGAAG
	TCCAATACTCCCTAAGCAACAGCACGCAAGCAGAGCTGCGACACCGCTTTCACGTGCA
	GAGGCATACATTGAGGCGAGGGACGAAGGTGTCTTTGGTTTAGCTAGCACCGCTAAAC
	TGCTGGTGGAGGTGACTGACGTGAACGATCATGCCCCCGAACTGGACTTCCTGACTCT
	TTCGAACCCAGTACCTGAGGACGCTGCCCCTGGCACAGTGATTGCTCTCTTTAGTGTA
	AAGGATGAAGACCTCGATTCTAATGGTAGGGTCATTTGTGGCATGTCTAGTGCAGGCC
	CTTTTCAGCTGACGGCTTCCTTTGACAACTACTACAGCCTGCTGATTGATGGGCCCCT
	GGACCGGGAGCAGATCAGTGAAAACCAAGTCCTGATCACGGCCTCAGATAGTGGCTCA
	CCGCCACTTAGCACCCGAAGGACAATCACTGTGTCAGTTGCTGATGTGAATGACAATA
	CACCAAACTTTCCTCAACCCCAGCAGGAACTTTTCGTTGCTGAAAACAATGGCCCTGG
	GGCCTCTCTAGGCCGAGTGTTTGCCCAGGACCCCGACCTGGGGAAGAATGGCCTTGTC
	TCTTATGAGCTGTTGGATGTTATCTCTGAAGGGCCATCAGCCTCTAGCTTGGTGGCAG
	TGGAATCATCCAGTGGGGCCATCACTGCCAAAACTTCCTTTGACTTTGAGCAGCTCAG
	GGGGTTTCATTTCCAAGTAGAAGGCCGGGATGGTGGCATTCCTCCCAGAAGTGCAACA
	GTGACTATAAACTTGTTTGTGGTAGATAGGAATGACAATTATCCGGTTATCTTGTTTC
	CCTTGCCCAGAAATGGTTCTGTCCCAGTGGAAATTGTGCCCCGCTCTGCCAGGACTGG
	ACACTTGGTCACAAAAGTGGTAGCAGAGGATGCTGACAGTGGTTCTAATGCCTGGCTT
	TCCTACCACATCTCCCGGGCGTCTGACTCTAGTCTCTTTAGAATTTCAGCCAATATAG
	GTGAGCTCCGTACTGCTCGCTTAGTTCTTCCCACTGATGCAGTTAAGCAGAGGGTGGT
	GGTAGTGGTTCGGGACCATGGAGACCCACCACTTTCCTCCTCTGTCACTCTGGGTGTG
	CTGTTGAGCAACTCTGTCCCTCAGTTACTTCCAGACTTTGAAGATGTCTGGGAACCAG
	GAGGGCAGCTTTCTGCCCAGAACTTGTATTTAGTCGAC
	ORF Start: at 7	ORF Stop: end of sequence
	SEQ ID NO: 122	688 aa	MW at 72305.7kD
NOV38b,	AGQLEYSVREETERGVAVGNLSADLRLPAAANSSRNFRFLSSHRELYFGVDLPSGNLV
CG110187-03
Protein Sequence	VREFADREQLCRAKAACVLTYDLVLEDPLELHKIRIHVLDTNDNSPLFPAGDVQLHIP
	EFLTPGARFTLPNAQDDDEGSNGILSYSLSPSQHFRLDMGSRVDGSEYPELVLEKALD
	REQRATHLLVLTARDGGLPARSGDAQVTIIVVDTNDNAPVFERSVYRTKVPETAPNGT
	VLFRVQALDPDEGSNGEVQYSLSNSTQAELRHRFHVHPKSGEVQVAASLGPFETLLEA
	YIEARDEGVFGLASTAKLLVEVTDVNDHAPELDFLTLSNPVPEDAAPGTVIALFSVKD
	EDLDSNGRVICGMSSAGPFQLTASFDNYYSLLIDGPLDREQISEYQVLITASDSGSPP
	LSTRRTITVSVADVNDNTPNFPQPQQELFVAENNGPGASLGRVFAQDPDLGKNGLVSY
	ELLDVISEGPSASSLVAVESSSGAITAKTSFDFEQLRGFHFQVEGRDGGIPPRSATVT
	INLFVVDRNDNYPVILFPLPRNGSVPVEIVPRSARTGHLVTKVVAEDADSGSNAWLSY
	HISRASDSSLFRISANIGELRTARLVLPTDAVKQRVVVVVRDHGDPPLSSSVTLGVLL
	SNSVPQLLPDFEDVWEPGGQLSAQNLYLVD

[0503] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 38B.

TABLE 38B
Comparison of NOV38a against NOV38b.
Protein	NOV38a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV38b	19 . . . 685	630/667 (94%)
	1 . . . 667	630/667 (94%)

[0504] Further analysis of the NOV38a protein yielded the following properties shown in Table 38C.

TABLE 38C
Protein Sequence Properties NOV38a
PSort     0.4600 probability located in plasma membrane;
analysis: 0.2400 probability located in nucleus; 0.1000 probability
          located in endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 19 and 20
analysis:

[0505] A search of the NOV38a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 38D.

TABLE 38D
Geneseq Results for NOV38a
		NOV38a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
ABG15234	Novel human diagnostic protein	8 . . . 963	480/984 (48%)	0.0
	#15225 - Homo sapiens, 1008 aa.	31 . . . 1008	637/984 (63%)
	[WO200175067-A2, 11-OCT-2001]
ABG15234	Novel human diagnostic protein	8 . . . 963	480/984 (48%)	0.0
	#15225 - Homo sapiens, 1008 aa.	31 . . . 1008	637/984 (63%)
	[WO200175067-A2, 11-OCT-2001]
AAM78649	Human protein SEQ ID NO: 1311 -	3 . . . 941	368/957 (38%)	e−170
	Homo sapiens, 931 aa.	9 . . . 931	526/957 (54%)
	[WO200157190-A2, 09-AUG-2001]
AAM79633	Human protein SEQ ID NO: 3279 -	3 . . . 941	370/962 (38%)	e−169
	Homo sapiens, 949 aa.	21 . . . 949	528/962 (54%)
	[WO200157190-A2, 09-AUG-2001]
ABB12315	Human protocadherin homologue,	3 . . . 941	370/962 (38%)	e−169
	SEQ ID NO: 2685 - Homo sapiens,	21 . . . 949	528/962 (54%)
	949 aa. [WO200157188-A2, 09-AUG-2001]

[0506] In a BLAST search of public sequence databases, the NOV38a protein was found to have homology to the proteins shown in the BLASTP data in Table 38E.

TABLE 38E
Public BLASTP Results for NOV38a
		NOV38a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9H158	Protocadherin alpha-C1 precursor	1 . . . 963	956/963 (99%)	0.0
	(PCDH-alpha-C1) - Homo sapiens	1 . . . 963	959/963 (99%)
	(Human), 963 aa.
Q91Y10	PROTOCADHERIN ALPHA C1 -	1 . . . 963	813/964 (84%)	0.0
	Mus musculus (Mouse), 964 aa.	1 . . . 964	873/964 (90%)
Q91Y09	PROTOCADHERIN ALPHA C2 -	16 . . . 963	484/980 (49%)	0.0
	Mus musculus (Mouse), 1006 aa.	37 . . . 1006	636/980 (64%)
Q9Y5I4	Protocadherin alpha C2 precursor	8 . . . 963	482/984 (48%)	0.0
	(PCDH-alpha-C2) - Homo sapiens	30 . . . 1007	639/984 (63%)
	(Human), 1007 aa.
Q9Y5H6	Protocadherin alpha 8 precursor	8 . . . 963	455/963 (47%)	0.0
	(PCDH-alpha8) - Homo sapiens	17 . . . 950	590/963 (61%)
	(Human), 950 aa.

[0507] PFam analysis predicts that the NOV38a protein contains the domains shown in the Table 38F.

TABLE 38F
Domain Analysis of NOV38a
		Identities/
Pfam	NOV38a	Similarities
Domain	Match Region	for the Matched Region	Expect Value
cadherin	129 . . . 224	31/110 (28%)	1.6e−10
		65/110 (59%)
cadherin	238 . . . 331	31/110 (28%)	6e−16
		66/110 (60%)
cadherin	345 . . . 436	36/107 (34%)	6.2e−10
		64/107 (60%)
cadherin	450 . . . 546	28/112 (25%)	5e−12
		67/112 (60%)
cadherin	566 . . . 657	28/108 (26%)	0.00086
		60/108 (56%)

Example 39

[0508] The NOV39 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 39A.

TABLE 39A
NOV39 Sequence Analysis
	SEQ ID NO: 123	3630 bp
NOV39a,	TGCGGCCGCGGAAAGAATGCGCGCCGCCCGTGCGCTCCGCCTGCCGCGTCTGGCCACC
CG110205-01
DNA Sequence	CGCAGCCGCCGCGTCCGCACCTGACCATGGAGTGCGCCCTCCTGCTCGCGTGTGCCTT
	CCCGGCTGCGGGTTCGGGCCCGCCGAGGGGCCTGGCGGGACTGGGGCGCGTGGCCAAG
	GCGCTCCAGCTGTGCTGCCTCTGCTGTGCGTCGGTCGCCGCGGCCTTAGCCAGTGACA
	GCAGCAGCGGCGCCAGCGGATTAAATGATGATTACGTCTTTGTCACGCCAGTAGAAGT
	AGACTCAGCCGGGTCATATATTTCACACGACATTTTGCACAACGGCAGGAAAAAGCGA
	TCGGCGCAGAATGCCAGAAGCTCCCTGCACTACCGATTTTCAGCATTTGGACAGGAAC
	TGCACTTAGAACTTAAGCCCTCGGCGATTTTGAGCAGTCACTTTATTGTCCAGGTACT
	TGGAAAAGATGGTGCTTCAGAGACTCAGAAACCCGAGGTGCAGCAATGCTTCTATCAG
	GGATTTATCAGAAATGACAGCTCCTCCTCTGTCGCTGTGTCTACGTGTGCTGGCTTGT
	CAGGTTTAATAAGGACACGAAAAAATGAATTCCTCATCTCGCCATTACCTCAGCTTCT
	GGCCCAGGAACACAACTACAGCTCCCCTGCGGGTCACCATCCTCACGTACTGTACAAA
	AGGACAGCAGAGGAGAAGATCCAGCGGTACCGTGGCTACCCCGGCTCTGGCCGGAATT
	ATCCTGGTTACTCCCCAAGTCACATTCCCCATGCATCTCAGAGTCGAGAGACAGAGTA
	TCACCATCGAAGGTTGCAAAAGCAGCATTTTTGTGGACGACGCAAGAAATATGCTCCC
	AAGCCTCCCACAGACGACACCTATCTAAGGTTTGATGAATATGGGAGCTCTGGGCGAC
	CCAGAAGATCAGCTGGAAAATCACAAAAGGGCCTCAATGTGGAAACCCTCGTGGTGGC
	AGACAAGAAAATGGTGGAAAAGCATGGCAAGGGAAATGTCACCACATACATTCTCACA
	GTAATGAACATGGTTTCTGGCCTATTTAAAGATGGGACTATTGGAAGTGACATAAACG
	TGGTTGTGGTGAGCCTAATTCTTCTGGAACAAGAACCTGGAGGATTATTGATCAACCA
	TCATGCAGACCAGTCTCTGAATAGTTTTTGTCAATGGCAGTCTGCCCTCATTGGAAAG
	AATGGCAAGAGACATGATCATGCCATCTTACTAACAGGATTTGATATTTGTTCTTGGA
	AGAATGAACCATGTGACACTCTAGGGTTTGCCCCCATCAGTGGAATGTGCTCTAAGTA
	CCGAAGTTGTACCATCAATGAGGACACAGGACTTGGCCTTGCCTTCACCATCGCTCAT
	GAGTCAGGGCACAACTTTGGTATGATTCACGATGGAGAAGGGAATCCCTGCAGAAAGG
	CTGAAGGCAATATCATGTCTCCCACACTGACCGGAAACAATGGAGTGTTTTCATGGTC
	TTCCTGCAGCCGCCAGTATCTCAAGAAATTCCTCAGCACACCTCAGGCGGGGTGTCTA
	GTGGATGAGCCCAAGCAAGCAGGACAGTATAAATATCCGGACAAACTACCAGGACAGA
	TTTATGATGCTGACACACAGTGTAAATGGCAATTTGGAGCAAAAGCCAAGTTATGCAG
	CCTTGGTTTTGTGAAGGATATTTGCAAATCACTTTGGTGCCACCGAGTAGGCCACAGG
	TGTGAGACCAAGTTTATGCCCGCAGCAGAAGGGACCGTTTGTGGCTTGAGTATGTGGT
	GTCGGCAAGGCCAGTGCGTAAAGTTTGGGGAGCTCGGGCCCCGGCCCATCCACGGCCA
	GTGGTCCGCCTGGTCGAAGTGGTCAGAATGTTCCCGGACATGTGGTGGAGGAGTCAAG
	TTCCAGGAGAGACACTGCAATAACCCCAAGCCTCAGTATGGTGGCTTATTCTGTCCAG
	GTTCTAGCCGTATTTATCAGCTGTGCAATATTAACCCTTGCAATGAAAATAGCTTGGA
	TTTTCGGGCTCAACAGTGTGCAGAATATAACAGCAAACCTTTCCGTGGATGGTTCTAC
	CAGTGGAAACCCTATACAAAAGTGGAAGAGGAAGATCGATGCAAACTGTACTGCAAGG
	CTGAGAACTTTGAATTTTTTTTTGCAATGTCCGGCAAACTGAAAGATGGAACTCCCTG
	CTCCCCAAACAAAAATGATGTTTGTATTGACGGGGTTTGTGAACTAGTGGGATGTGAT
	CATGAACTAGGCTCTAAAGCAGTTTCAGATGCTTGTGGCGTTTGCAAAGGTGATAATT
	CAACTTGCAAGTTTTATAAAGGCCTGTACCTCAACCAGCATAAAGCAAATGAATATTA
	TCCGGTGGTCCTCATTCCAGCTGGCGCCCGAAGCATCGAAATCCAGGAGCTGCAGGTT
	TCCTCCAGTTACCTCGCAGTTCGAAGCCTCAGTCAAAAGTATTACCTCACCGGGGGCT
	GGAGCATCCACTGGCCTGGGGAGTTCCCCTTCGCTGGGACCACGTTTGAATACCAGCG
	CTCTTTCAACCGCCCGGAACGTCTGTACGCGCCAGGGCCCACAAATGAGACGCTGATT
	CTGATGCAAGGCAAAAATCCAGGGATAGCTTGGAAGTATGCACTTCCCAAGGTCATGA
	ATGGAACTCCACCAGCCACAAAAAGACCTGCCTATACCTGCTGGATGCCAGGTGAATG
	GAGTACATGCAGCAAGGCCTGTGCTGGAGGCCAGCAGAGCCGAAAGATCCAGTGTGTG
	CAAAAGAAGCCCTTCCAAAAGGAGGAAGCAGTGTTGCATTCTCTCTGTCCAGTGAGCA
	CACCCACTCAGGTCCAAGCCTGCAACAGCCATGCCTGCCCTCCACAATGGAGCCTTGG
	ACCCTGGTCTCAGTGTTCCAAGACCTGTGGACGAGGGGTGAGGAAGCGTGAACTCCTC
	TGCAAGGGCTCTGCCGCAGAAACCCTCCCCGAGAGCCAGTGTACCAGTCTCCCCAGAC
	CTGAGCTGCAGGAGGGCTGTGTGCTTGGACGATGCCCCAAGAACAGCCGGCTACAGTG
	GGTCGCTTCTTCGTGGAGCGAGTGTTCTGCAACCTGTGGTTTGGGTGTGAGGAAGAGG
	GAGATGAAGTGCAGCGAGAAGGGCTTCCAGGGAAAGCTGATAACTTTCCCAGAGCGAA
	GATGCCGTAATATTAAGAAACCAAATCTGGACTTGGAAGAGACCTGCAACCGACGGGC
	TTGCCCAGCCCATCCAGTGTACAACATGGTAGCTGGATGGTATTCATTGCCGTGGCAG
	CAGTGCACAGTCACCTGTGGGGGAGGGGTCCAGACCCGGTCAGTCCACTGTGTTCAGC
	AAGGCCGGCCTTCCTCAAGTTGTCTGCTCCATCAGAAACCTCCGGTGCTACGAGCCTG
	TAATACAAACTTCTGTCCAGCTCCTGAAAAGAGAGAGGATCCATCCTGCGTAGATTTC
	TTCAACTGGTGTCACCTAGTTCCTCAGCATGGTGTCTGCAACCACAAGTTTTACGGAA
	AACAATGCTGCAAGTCATGCACAAGGAAGATCTGATCTTGGTGTCCTCCCCAGCACCT
	TATGGCCAGGGGCTTACCTTTCAACCTCTAGAGA
	ORF Start: ATG at 85	ORF Stop: TGA at 3571
	SEQ ID NO: 124	1162 aa	MW at 128776kD
NOV39a,	MECALLLACAFPAAGSGPPRGLAGLGRVAKALQLCCLCCASVAAALASDSSSGASGLN
CG110205-01
Protein Sequence	DDYVFVTPVEVDSAGSYISIDILHNGRKKRSAQNARSSLHYRFSAFGQELHLELKPSA
	ILSSHFIVQVLGKDGASETQKPEVQQCFYQGFIRNDSSSSVAVSTCAGLSGLIRTRKN
	EFLISPLPQLLAQEHNYSSPAGHHPHVLYKRTAEEKIQRYRGYPGSGRNYPGYSPSHI
	PHASQSRETEYHHRRLQKQHFCGRRKKYAPKPPTEDTYLRFDEYGSSGRPRRSAGKSQ
	KGLNVETLVVADKKMVEKHGKGNVTTYILTVMNNVSGLFKDGTIGSDINVVVVSLILL
	EQEPGGLLINHHADQSLNSFCQWQSALIGKNGKRHDHAILLTGFDICSWKNEPCDTLG
	FAPISGMCSKYRSCTINEDTGLGLAFTIAHESGHNFGMIHDGBGNPCRKAEGNIMSPT
	LTGNNGVFSWSSCSRQYLKKFLSTPQAGCLVDEPKQAGQYKYPDKLPGQIYDADTQCK
	WQFGAKAKLCSLGFVKDICKSLWCHRVGHRCETKFMPAAEGTVCGLSMWCRQGQCVKF
	GELGPRPIHGQWSAWSKWSECSRTCGGGVKFQERHCNNPKPQYGGLFCPGSSRIYQLC
	NINPCNENSLDFRAQQCAEYNSKPFRGWFYQWKPYTKVEEEDRCKLYCKAENFEFFFA
	MSGKVKDGTPCSPNKNDVCIDGVCELVGCDHELGSKAVSDACGVCKGDNSTCKFYKGL
	YLNQHKANEYYPVVLIPAGARSIEIQELQVSSSYLAVRSLSQKYYLTGGWSIDWPGEF
	PFAGTTFEYQRSFNRPERLYAPGPTNETLILMQGKNPGIAWKYALPKVMNGTPPATKR
	PAYTCWMPGEWSTCSKACAGGQQSRKIQCVQKKPFQKEEAVLHSLCPVSTPTQVQACN
	SHACPFQWSLGPWSQCSKTCGRGVRKRELLCKGSAAETLPESQCTSLPRPELQEGCVL
	GRCPKNSRLQWVASSWSECSATCGLGVRKREMKCSEKGFQGKLITFPERRCRNIKKPN
	LDLEETCNRRACPAHPVYNMVAGWYSLPWQQCTVTCGGGVQTRSVHCVQQGRPSSSCL
	LHQKPPVLRACNTNFCPAPEKREDPSCVDFFNWCHLVPQHGVCNHKFYGKQCCKSCTR
	KI
	SEQ ID NO: 125	1059 bp
NOV39b,	AAGCTTGTGGAAACCCTCGTGGTGGCAGACAAGCAAATGGTGGAAAAGCATGGCAAGG
CG110205-02
DNA Sequence	GAAATGTCACCACATACATTCTCACAGTAATGAACATGGTTTCTGGCCTATTTAAAGA
	TGGGACTATTGGAAGTGACATAAACGTGGTTGTGGTGAGCCTAATTCTTCTGGAACAA
	GAACCTGGAGGATTATTGATCAACCATCATGCAGACCAGTCTCTGAATAGTTTTTGTC
	AATGGCAGTCTGCCCTCATTGGAAAGAATGGCAAGAGACATGATCATGCCATCTTACT
	AACAGGATTTGATATTTGTTCTTGGAAGAATGAACCATGTGACACTCTAGGGTTTGCC
	CCCATCAGTGGAATGTGCTCTAAGTACCGAAGTTGTACCATCAATGAGGACACAGGAC
	TTGGCCTTGCCTTCACCATCGCTCATGAGTCAGGGCACAACTTTGGTATGATTCACGA
	CGGAGAAGGGAATCCCTGCAGAAAGGCTGAAGGCAATATCATGTCTCCCACACTGACC
	GGAAACAATGGAGTGTTTTCATGGTCTTCCTGCAGCCGCCAGTATCTCAAGAAATTCC
	TCAGCACACCTCAGGCGGGGTGTCTAGTGGATGAGCCCAAGCAAGCAGGACAGTATAA
	ATATCCGGACAAACTACCAGGACAGATTTATGATGCTGACACACTGTGTAAATGGCAA
	TTTGGAGCAAAAGCCAAGTTATGCAGCCTTGGTTTTGTGAAGGATATTTGCAAATCAC
	TTTGGTGCCACCGAGTAGGCCACAGGTGTGAGACCAAGTTTATGCCCGCAGCAGAAGG
	GACCGTTTGTGGCTTGAGTATGTGGTGTCGGCAAGGCCAGTGCGTAAAGTTTGGGGAG
	CTCGGGCCCCGGCCCATCCACGGCCAGTGGTCCGCCTGGTCGAAGTGGTCAGAATGTT
	CCCGGACATGTGGTGGAGGAGTCAAGTTCCAGGAGAGACACTGCAATAACCCCAAGCC
	TCAGTATGGTGGCTTGTTCTGTCCAGGTTCTAGCCGTATTTATCAGCTGTGCAATATT
	AACCCTTGCCTCGAG
	ORF Start: at 7	ORF Stop: at 1054
	SEQ ID NO: 126	349 aa	MW at 38372.7kD
NOV39b,	VETLVVADKQMVEKHGKGNVTTYILTVMNMVSGLFKDGTIGSDINVVVVSLILLEQEP
CG110205-02
Protein Sequence	GGLLINHHADQSLNSFCQWQSALIGKNGKRHDHAILLTGFDICSWKNEPCDTLGFAPI
	SGMCSKYRSCTINEDTGLGLAFTIAHESGHNFGMIHDGEGNPCRKAEGNIMSPTLTGN
	NGVFSWSSCSRQYLKKFLSTPQAGCLVDEPKQAGQYKYPDKLPGQIYDADTLCKWQFG
	AKAKLCSLGFVKDICKSLWCHRVGHRCETKFMPAAEGTVCGLSMWCRQGQCVKFGELG
	PRPIHGQWSAWSKWSECSRTCGGGVKFQERHCNNPKPQYGGLFCPGSSRIYQLCNINP
	C
	SEQ ID NO: 127	1059 bp
NOV39c,	AAGCTTGTGGAAACCCTCGTGGTGGCAGACAAGCAAATGGTGGAAAAGCATGGCAAGG
207756942 DNA
Sequence	GAAATGTCACCACATACATTCTCACAGTAATGAACATGGTTTCTGGCCTATTTAAAGA
	TGGGACTATTGGAAGTGACATAAACGTGGTTGTGGTGAGCCTAATTCTTCTGGAACAA
	GAACCTGGAGGATTATTGATCAACCATCATGCAGACCAGTCTCTGAATAGTTTTTGTC
	AATGGCAGTCTGCCCTCATTGGAAAGAATGGCAAGAGACATGATCATGCCATCTTACT
	AACAGGATTTGATATTTGTTCTTGGAAGAATGAACCATGTGACACTCTAGGGTTTGCC
	CCCATCAGTGGAATGTGCTCTAAGTACCGAAGTTGTACCATCAATGAGGACACAGGAC
	TTGGCCTTGCCTTCACCATCGCTCATGAGTCAGGGCACAACTTTGGTATGATTCACGA
	CGGACAAGGGAATCCCTGCAGAAAGGCTGAAGGCAATATCATGTCTCCCACACTGACC
	GGAAACAATGGAGTGTTTTCATGGTCTTCCTGCAGCCGCCAGTATCTCAAGAAATTCC
	TCAGCACACCTCAGGCGGGGTGTCTAGTGGATGAGCCCAAGCAAGCAGGACAGTATAA
	ATATCCGGACAAACTACCAGGACAGATTTATGATGCTGACACACAGTGTAAATGGCAA
	TTTGGAGCAAAAGCCAAGTTATGCAGCCTTGGTTTTGTGAAGGATATTTGCAAATCAC
	TTTGGTGCCACCGAGTAGGCCACAGGTGTGAGACCAAGTTTATGCCCGCAGCAGAAGG
	GACCGTTTGTGGCTTGAGTATGTGGTGTCGGCAAGGCCAGTGCGTAAAGTTTGGGGAG
	CTCGGGCCCCGGCCCATCCACGGCCAGTGGTCCGCCTGGTCGAAGTGGTCAGAATGTT
	CCCGGACATGTGGTGGAGGAGTCAAGTTCCAGGAGAGACACTGCAATAACCCCAAGCC
	TCAGTATGGTGGCTTATTCTGTCCAGGTTCTAGCCGTATTTATCAGCTGTGCAATATT
	AACCCTTGCCTCGAG
	ORF Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 128	353 aa	MW at 38871.3kD
NOV39c,	KLVETLVVADKQMVEKHGKGNVTTYILTVMNMVSGLFKDGTIGSDINVVVVSLILLEQ
207756942
Protein Sequence	EPGGLLINHHADQSLNSFCQWQSALIGKNGKRHDHAILLTGFDICSWKNEPCDTLGFA
	PISGMCSKYRSCTINEDTGLGLAFTIAHESGHNFGMIHDGEGNPCRKAEGNIMSPTLT
	GNNGVFSWSSCSRQYLKKFLSTPQAGCLVDEPKQAGQYKYPDKLPGQIYDADTQCKWQ
	FGAKAKLCSLGFVKDICKSLWCHRVGHRCETKFMPAAEGTVCGLSMWCRQGQCVKFGE
	LGPRPIHGQWSAWSKWSECSRTCGGGVKFQERHCNNPKPQYGGLFCPGSSRIYQLCNI
	NPCLE
	SEQ ID NO: 129	1059 bp
NOV39d,	AAGCTTGTGGAAACCCTCGTGGTGGCAGACAAGAAAATGGTGGAAAAGCATGGCAAGG
207756946 DNA
Sequence	GAAATGTCACCACATACATTCTCACAGTAATGAACATGGTTTCTGGCCTATTTAAAGA
	TGGGACTATTGGAAGTGACATAAACGTGGTTGTGGTGAGCCTAATTCTTCTGGAACAA
	GAACCTGGAGGATTATTGATCAACCATCATGCAGACCAGTCTCTGAATAGTTTTTGTC
	AATGGCAGTCTGCCCTCATTGGAAAGAATGGCAAGAGACATGATCATGCCATCTTACT
	AACAGGATTTGATATTTGTTCTTGGAAGAATGAACCATGTGACACTCTAGGGTTTGCC
	CCCATCAGTGGAATGTGCTCTAAGTACCGAAGTTGTACCATCAATGAGGACACAGGAC
	TTGGCCTTGCCTTCACCATCGCTCATGAGTCAGGGCACAACTTTGGTATGATTCACGA
	CGGAGAAGGGAATCCCTGCAGAAAGGCTGAAGGCAATATCATGTCTCCCACACTGACC
	GGAAACAATGGAGTGTTTTCATGGTCTTCCTGCAGCCGCCAGTATCTCAAGAAATTCC
	TCAGCACACCTCAGGCGGGGTGTCTAGTGGATGAGCCCAAGCAAGCAGGACAGTATAA
	ATATCCGGACAAACTACCAGGACAGATTTATGATGCTGACACACAGTGTAAATGGCAA
	TTTGGAGCAAAAGCCAAGTTATGCAGCCTTGGTTTTGTGAAGGATATTTGCAAATCAC
	TTTGGTGCCACCGGGTAGGCCACAGGTGTGAGACCAAGTTTATGCCCGCAGCAGAAGG
	GACCGTTTGTGGCTTGAGTATGTGGTGTCGGCAAGGCCAGTGCGTAAAGTTTGGGGAG
	CTCGGGCCCCGGCCCATCCACGGCCAGTGGTCCGCCTGGTCGAAGTGGTCAGAATGTT
	CCCGGACATGTGGTGGAGGAGTCAAGTTCCAGGAGAGACACTGCAATAACCCCAAGCC
	TCAGTATGGTGGCATATTCTGTCCAGGTTCTAGCCGTATTTATCAGCTGTGCAATATT
	AACCCTTGCCTCGAG
	ORF Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 130	353 aa	MW at 38871.3kD
NOV39d,	KLVETLVVADKKMVEKHGKGNVTTYILTVMNMVSGLFKDGTIGSDINVVVVSLILLEQ
207756946
Protein Sequence	EPGGLLINHHADQSLNSFCQWQSALIGKNGKRHDHAILLTGFDICSWKNEPCDTLGFA
	PISGMCSKYRSCTINEDTGLGLAFTIAHESGHNFGMIHDGEGNPCRKAEGNIMSPTLT
	GNNGVFSWSSCSRQYLKKFLSTPQAGCLVDEPKQAGQYKYPDKLPGQIYDADTQCKWQ
	FGAKAKLCSLGFVKDICKSLWCHRVGHRCETKFMPAAEGTVCGLSMWCRQGQCVKFGE
	LGPRPIHGQWSAWSKWSECSRTCGGGVKFQERHCNNPKPQYGGIFCPGSSRIYQLCNI
	NPCLE
	SEQ ID NO: 131	1059 bp
NOV39e,	AAGCTTGTGGAAACCCTCGTGGTGGCAGACAAGAAAATGGTGGAAAAGCATGGCAAGG
207756950 DNA
Sequence	GAAATGTCACCACATACATTCTCACAGTAATGAACATGGTTTCTGGCCTATTTAAAGA
	TGGGACTATTGGAAGTGACATAAACGTGGTTGTGGTGAGCCTAATTCTTCTGGAACAA
	GAACCTGGAGGATTATTGATCAACCATCATGCAGACCAGTCTCTGAATAGTTTTTGTC
	AATGGCAGTCTGCCCTCATTGGAA~GAATGGCAAGAGACATGATCATGCCATCTTACT
	AACAGGATTTGATATTTGTTCTTGGAAGAATGAACCATGTGGCACTCTAGGGTTTGCC
	CCCATCAGTGGAATGTGCTCTAAGTACCGAAGTTGTACCATCAATGAGGACACAGGAC
	TTGGCCTTGCCTTCACCATCGCTCATGAGTCAGGGCACAACTTTGGTATGATTCACGA
	CGGAGAAGGGAATCCCTGCAGAAAGGCTGAAGGCAATATCATGTCTCCCACACTGACC
	GGAAACAATGGAGTGTTTTCATGGTCTTCCTGCAGCCGCCAGTATCTCAAGAAATTCC
	TCAGCACACCTCAGGCGGGGTGTCTAGTGGATGAGCCCAAGCAAGCAGGACAGTATAA
	ATATCCGGACAAACTACCAGGACAGATTTATGATGCTGACACACAGTGTAAATGGCAA
	TTTGGAGCAAAAGCCA~GTTATGCAGCCTTGGTTTTGTGGAGGATATTTGCAAATCAC
	TTTGGTGCCACCGAGTAGGCCACAGGTGTGAGACCAAGTTTATGCCCGCAGCAGAAGG
	GACCGTTTGTGGCTTGAGTATGTGGTGTCGGCAAGGCCAGTGCGTAAAGTTTGGGGAG
	CTCGGGCCCCGGCCCATCCACGGCCAGTGGTCCGCCTGGTCGAATTGGTCAGAATGTT
	CCCGGACATGTGGTGGAGGAGTCAAGTTCCAGGAGAGACACTGCAATAACCCCAAGCC
	TCAGTATGGTGGCATATTCTGTCCAGGTTCTAGCCGTATTTATCAGCTGTGCAATATT
	AACCCTTGCCTCGAG
	ORF Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 132	353 aa	MW at 38800.1kD
NOV39e,	KLVETLVVADKKMVEKHGKGNVTTYILTVMMMVSGLFKDGTIGSDINVVVVSLILLEQ
207756950
Protein Sequence	EPGGLLINHHADQSLNSFCQWQSALIGKNGKRHDHAILLTGFDICSWKNEPCGTLGFA
	PISGMCSKYRSCTINEDTGLGLAFTIAHESGHNFGMIHDGEGNPCRKAEGNIMSPTLT
	GNNGVFSWSSCSRQYLKKFLSTPQAGCLVDEPKQAGQYKYPDKLPGQIYDADTQCKWQ
	FGAKAKLCSLGFVEDICKSLWCHRVGHRCETKFMPAAEGTVCGLSMWCRQGQCVKFGE
	LGPRPIHGQWSAWSNWSECSRTCGGGVKFQERHCNNPKPQYGGIFCPGSSRIYQLCNI
	NPCLE
	SEQ ID NO: 133	1059 bp
NOV39f,	AAGCTTGTGGAAACCCTCGTGGTGGCAGACAAGAAAATGGTGGAAAAGCATGGCAAGG
207756966 DNA
Sequence	GAAATGTCACCACATACATTCTCACAGTAATGAACATGGTTTCTGGCCTATTTAAAGA
	TGGGACTATTGGAAGTGACATAAACGTGGTTGTGGTGAGCCTAATGCTTCTGGAACAA
	GAACCTGGAGGATTATTGATCAACCATCATGCAGACCAGTCTCTGAATAGTTTTTGTC
	AATGGCAGTCTGCCCTCATTGGAAAGAATGGCAAGAGACATGATCATGCCATCTTACT
	AACAGGATTTGATATTTGTTCTTGGAAGAATGAACCATGTGACACTCTAGGGTTTGCC
	CCCATCAGTGGAATGTGCTCTAAGTACCGAAGTTGTACCATCAATGAGGACACAGGAC
	TTGGCCTTGCCTTCACCATCGCTCATGAGTCAGGGCACAACTTTGGTATGATTCACGA
	CGGAGAAGGGAATCCCTGCAGAAAGGCTGAAGGCAATATCATGTCTCCCACACTGACC
	GGAAACAATGGAGTGTTTTCATGGTCTTCCTGCAGCCGCCAGTATCTCAAGAAATTCC
	TCAGCACACCTCAGGCGGGGTGTCTAGTGGATGAGCCCAAGCAAGCAGGACAGTATAA
	ATATCCGGACAAACTACCAGGACAGATTTATGATGCTGACACACAGTGTAAATGGCAA
	TTTGGAGCAAAAGCCAAGTTATGCAGCCTTGGTTTTGTGAAGGATATTTGCAAATCAC
	TTTGGTGCCACCGAGTAGGCCACAGGTGTGAGACCAAGTTTATGCCCGCAGCAGAAGG
	GACCGTTTGTGGCTTGAGTATGTGGTGTCGGCAAGGCCAGTGCGTAAAGTTTGGGGAG
	CTCGGGCCCCGGCCCATCCACGGCCAGTGGTCCGCCTGGTCGAAGTGGTCAGAATGTT
	CCCGGACATGTGGTGGAGGAGTCAAGTTCCAGGAGAGACACTGCAATAACCCCAAGCC
	TCAGTATGGTGGCATATTCTGTCCAQGTTCTAGCCGTATTTATCAGCTGTGCAATATT
	AACCCTTGCCTCGAG
	ORF Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 134	353 aa	MW at 38889.3kD
NOV39f,	KLVETLVVADKKMVEKHGKGNVTTYILTVD4NMVSGLFKDGTIGSDINVVVSLMLLEQ
207756966
Protein Sequence	EPGGLLINHHADQSLNSFCQWQSALIGKNGKRHDHAILLTGFDICSWKNEPCDTLGFA
	PISGMCSKYRSCTINEDTGLGLAFTIAHESGHNFGMIHDGEGNPCRKAEGNIMSPTLT
	GNNGVFSWSSCSRQYLKKFLSTPQAGCLVDEPKQAGQYKYPDKLPGQIYDADTQCKWQ
	FGAKAKLCSLGFVKDICKSLWCHRVGHRCETKFMPAAEGTVCGLSMWCRQGQCVKFGE
	LGPRPIHGQWSAWSKWSECSRTCGGGVKFQERHCNNPKPQYGGIFCPGSSRIYQLCNI
	NPCLE

[0509] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 39B.

TABLE 39B
Comparison of NOV39a against NOV39b through NOV39f.
	NOV39a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV39b	295 . . . 643	347/349 (99%)
	1 . . . 349	348/349 (99%)
NOV39c	295 . . . 645	349/351 (99%)
	3 . . . 353	350/351 (99%)
NOV39d	295 . . . 645	349/351 (99%)
	3 . . . 353	350/351 (99%)
NOV39e	295 . . . 645	346/351 (98%)
	3 . . . 353	348/351 (98%)
NOV39f	295 . . . 645	348/351 (99%)
	3 . . . 353	350/351 (99%)

[0510] Further analysis of the NOV39a protein yielded the following properties shown in Table 39C.

TABLE 39C
Protein Sequence Properties NOV39a
PSort     0.6400 probability located in plasma membrane;
analysis: 0.4600 probability located in Golgi body; 0.3700 probability
          located in endoplasmic reticulum (membrane);
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 48 and 49
analysis:

[0511] A search of the NOV39a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 39D.

TABLE 39D
Geneseq Results for NOV39a
		NOV39a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAU72893	Human metalloprotease partial	305 . . . 1162	856/934 (91%)	0.0
	protein sequence #5 - Homo	1 . . . 934	858/934 (91%)
	sapiens, 934 aa. [WO200183782-
	A2, 08-NOV-2001]
AAU72891	Human metalloprotease partial	20 . . . 1160	660/1238 (53%)	0.0
	protein sequence #3 - Homo	9 . . . 1221	828/1238 (66%)
	sapiens, 1224 aa. [WO200183782-
	A2, 08-NOV-2001]
AAU72890	Human metalloprotease partial	59 . . . 1158	415/1134 (36%)	0.0
	protein sequence #2 - Homo	37 . . . 1100	585/1134 (50%)
	sapiens, 1103 aa. [WO200183782-
	A2, 08-NOV-2001]
AAB74945	Human ADAM type metal protease	59 . . . 1158	413/1134 (36%)	0.0
	MDTS2 protein SEQ ID NO: 10 -	37 . . . 1100	585/1134 (51%)
	Homo sapiens, 1103 aa.
	[JP2001008687-A, 16-JAN-2001]
AAB47719	ADAMTS-E - Homo sapiens, 1104	59 . . . 1158	412/1134 (36%)	0.0
	aa. [EP1149903-A1, 31-OCT-2001]	37 . . . 1101	583/1134 (51%)

[0512] In a BLAST search of public sequence databases, the NOV39a protein was found to have homology to the proteins shown in the BLASTP data in Table 39E.

TABLE 39E
Public BLASTP Results for NOV39a
		NOV39a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
CAC83612	ADAMTS18 PROTEIN - Homo	1 . . . 1073	937/1081 (86%)	0.0
	sapiens (Human), 1081 aa.	1 . . . 1064	965/1081 (88%)
CAC86015	METALLOPROTEASE	20 . . . 1007	576/1081 (53%)	0.0
	DISINTEGRIN 16 WITH	9 . . . 1065	719/1081 (66%)
	THROMBOSPONDIN TYPE I
	MOTIF - Homo sapiens (Human),
	1072 aa.
Q9H324	ADAMTS-10 precursor (EC 3.4.24.—)	59 . . . 1158	412/1134 (36%)	0.0
	(A disintegrin and	11 . . . 1074	584/1134 (51%)
	metalloproteinase with
	thrombospondin motifs 10)
	(ADAM-TS 10) (ADAM-TS10) -
	Homo sapiens (Human), 1077 aa
	(fragment).
CAD20434	SEQUENCE 8 FROM PATENT	59 . . . 1101	398/1074 (37%)	0.0
	WO0188156 - Homo sapiens	37 . . . 1041	558/1074 (51%)
	(Human), 1044 aa (fragment).
P58397	ADAMTS-12 precursor (EC 3.4.24.—)	60 . . . 1058	375/1026 (36%)	0.0
	(A disintegrin and	51 . . . 997	548/1026 (52%)
	metalloproteinase with
	thrombospondin motifs 12)
	(ADAM-TS 12) (ADAM- TS12) -
	Homo sapiens (Human), 1593 aa.

[0513] PFam analysis predicts that the NOV39a protein contains the domains shown in the Table 39F.

TABLE 39F
Domain Analysis of NOV39a
		Identities/
	NOV39a	Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
Pep_M12B_propep	111 . . . 222	27/119 (23%)	1.6e−13
		72/119 (61%)
Reprolysin	295 . . . 498	66/221 (30%)	1.1e−21
		158/221 (71%)
tsp_1	593 . . . 643	23/54 (43%)	1.2e−12
		36/54 (67%)
tsp_1	879 . . . 932	13/60 (22%)	0.0042
		39/60 (65%)
tsp_1	934 . . . 989	18/64 (28%)	0.022
		36/64 (56%)
tsp_1	997 . . . 1056	18/64 (28%)	0.015
		39/64 (61%)
tsp_1	1072 . . . 1118	14/55 (25%)	0.0041
		34/55 (62%)

Example 40

[0514] The NOV40 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 40A.

TABLE 40A
NOV40 Sequence Analysis
                 SEQ ID NO:135        3107 bp
NOV40a           CGTGGAGGTTCTTGTCCAGGGCACATGGAGGACCGTGTGTTGCGTGACGACCTCTGGA
CG110242-01      ATCTGGCCAAGGCCACTGTCGTGTGCCGCCAGCTACAGTGTGGACGGGCTGTGGCAGC
DNA Sequence     CCCAACAGGGGCTCACTTCGGGGCAGGCTCTGGGAAAATCCTGCTGGATGACGTGCAG
                 TGTGTGGGGAGCGAGAGCCACCTGGGGCAGTGCGTGCATGGGGGCCGGGCCAGGCACA
                 ACTGTGGGCACCTGGAGGATGCCAGTGTCATCTGTTCAAGGCCACTCCCCAGTGTCCC
                 TACTTCTTGTGCCTCCCCAGGAGCCTGGATGGAGGTGAGGCTGCTGAACGGCACAGGA
                 AGGTGCTCAGGCCGTGTGGAAGTTCTCGTCCAGGGCACGTGGGGGACCGTGTGTGATG
                 ATCTCTGGGACCTGGCTGAGGCCACTGTCGTGTGCCGCCAGCTGCAGTGTGGCCAGGC
                 TGTGGCAGCCCCCACAGGGGCCCACTTTCGGGCAGGCTCTGGGAAGATCTTACTGGAT
                 GACATGCAGTGTGTGGGCAGTGAGAGCCATCTGGGTCAATGCATGCGTGGGGACCAGG
                 CCAGGCACAACTGTGGGCACCTGGAGGATGCCAGTGTCATCTGCACACACCATCAGTT
                 ACCAGCTGCAGGAGCCTGCATGGAGGTGAGGCTGCTGAATGGCACAGGGAGGTGCTTA
                 GGCCGCGTGGAGGTTCTCATCCAGGGCACGTGGGGGACGGTGTGTGACCACTTCTGGA
                 ACCTGGCCGAGGCCGCCGTTGTGTGCCGCCAGCTGCAATGTGGCCAGGCCATGGCAGC
                 CCACTTCGGGGCAAGCTCTGGGAAAGTCCTGCTGGATGACATGCAGTGTGTGGGCAGC
                 AAGAGCCACCTGGGGCGGTGCGTGCACAGGGGCTGGGCCAGGCACAACTGTGGGCACC
                 TGGAGGATGCCAGTGTCATCTGTGCAGAAAAATCTCGGTGTGGTGGCATTATTACCAA
                 CTCATCTGGAGCGATTAGGAATCCCCCACAGAATGAAATGCATGACAACATCACTTGT
                 GTGTGGGAAATCAAGGCAAATGCATCTGATCATATACTGCTGGCATTTCCACATCTTC
                 TTGACTGCACCAATGAATATTTTGAAATCCTGGACGGTCCACCATCCTCAGTAAAGTC
                 ATTGGGGAGGACCTGCTCTGGCTTCCAACACACCTACATCTCCTCCTCCAGCTCAATG
                 ACCCTCGTGTATTTCCGAAGCTTCAACAACCTAGGAAAATGGCTATTGACGATGTATT
                 TCCTTGTACTTGCAGAGGCAGTGTTGCAGACCCCACATCTAATCAGTCAGTGCCCCCA
                 GAGGACAACAGTCACCAGATCTCTCTCTGCAGGGGACTGGCCGGAGCTGCAGCTGGTG
                 GGTGGCTCTGGCCGGTGCTCAGGACGCGTGGAGATTCTCCACCAGGGCGCCTGGGGCA
                 CCGTGTGTGATGACCTGTGGGACCTGAACGAAGCTGAGGTTGTGTGCCGGCAGCTTGG
                 GTGTGGTCGAGCCATGTCTGCCCTTGGAAAGGCCCACTTTGGCCCCGGCTCAGGAGAC
                 ATCTTCCTGGACAACCTCCAGTGCGCTGGTGTGGAGCGCTACCTGGGCCAGTGCACCC
                 ACTCGGGCTGGTCAGAGCACAACCATGTTTCATATTCAGGCATAATTTCCACTTCAGA
                 AGAAGTAACTCCTTCACCTGGTTGTGGCGGTTACCTGGATACCTTGGAAGGATCCTTC
                 ACCAGCCCCAATTACCCAAAGCCGCATCCTGAGCTGGCTTATTGTGTGTGGCACATAC
                 AAGTGGAGAAAGATTACAAGATAAAACTAAACTTCAAAGAGATTGAAATAGACAAACA
                 GTGCAAATTTGATTTTCTTGCCATCTATGATGGCCCCTCCACCAACTCTGGCCTGATT
                 GGACAAGTCTGTGGCCGTGTGACTCCCACCTTCGAATCGTCATCAAACTCTCTGACTG
                 TCGTGTTGTCTACAGATTATGCCAATTCTTACCGGGGATTTTCTGCTTCCTACACCTC
                 AATTTATGCAGAAAACATCACAGCATCTTTAACTTGCTCTTCTGACAGGATGAGAGTT
                 ATTATAAGCAAATCCTACCTAGAGGCTTTTAACTCTAATGGGAATAACTTGCAACTAA
                 AAGACCCAACTTGCAGACCAAAATTATCAAATGTTGTGGAATTTTCTGTCCCTCTTAA
                 TGGATGTGGTACAATCAGACAGGTAGAAGATCAGTCAATTACTTACACCAATATAATC
                 ACCTTTTCTGCATCCTCAACTTCTGAAGTGATCACCCGTCAGAAACAACTCCAGATTA
                 TTGTGAAGTGTGAAATGGGACATAATTCTACAGTGGAGATAATATACATAACAGAAGA
                 TGATGTAATACAAAGTCAAAATGCACTGGGCAAATATAACACCAGCATGGCTCTTTTT
                 GAATCCAATTCATTTGAAAAGACTATACTTGAATCACCATATTATGTGGATTTGAACC
                 AAACTCTTTTTGTTCAAGTTAGTCTGCACACCTCAGATCCAAATTTGGTGGTGTTTCT
                 TGATACCTGTAGAGCCTCTCCCACCTCTGACTTTGCATCTCCAACCTACGACCTAATC
                 AAGAGTGGGTGTAGTCGAGATGAAACTTGTAAGGTGTATCCCTTATTTGGACACTATG
                 GGAGATTCCAGTTTAATGCCTTTAAATTCTTGAGAAGTATGAGCTCTGTGTATCTGCA
                 GTGTAAAGTTTTGATATGTGATAGCAGTGACCACCAGTCTCGCTGCAATCAAGGTTGT
                 GTCTCCAGAAGCAAACGAGACATTTCTTCATATAAATGGAAAACAGATTCCATCATAG
                 GACCCATTCGTCTGAAAAGGGATCGAAGTGCAAGTGGCAATTCAGGATCTCAGCATGA
                 AACACATGCGGAAGAAACTCCAAACCAGCCTTTCAACAGTGTGCATCTGTTTTCCTTC
                 ATGGTTCTAGCTCTGAATGTGGTGACTGTAGCGACAATCACAGTGAGGCATTTTGTAA
                 ATCAACGGGCAGACTACAAATACCAGAAGCTGCAGAACTATTAACTAACAGGTCCAAC
                 CCTAAGTGAGACATGTTTCTCCAGGATGCCAAA
                 ORF Start: ATG at 25 ORF Stop: TAA at 3058
                 SEQ ID NO:136        1011 aa MW at 110883.1 kD
NOV40a,          MEDRVLRDDLWNLAKATVVCRQLQCGRAVAAPTGAHFGAGSGKILLDDVQCVGSESHL
CG110242-01      GQCVHGGRARHNCGHLEDASVICSRPLPSVPTSCASPGAWMEVRLLNGTGRCSGRVEV
Protein Sequence LVQGTWGTVCDDLWDLAEATVVCRQLQCGQAVAAPTGAHFRAGSGKILLDDMQCVGSE
                 SHLGQCMRGDQARHNCGHLEDASVICTHHQLPAAGACMEVRLLNGTGRCLGRVEVLIQ
                 GTWGTVCDHFWNLAEAAVVCRQLQCGQAMAAHFGASSGKVLLDDMQCVGSKSHLGRCV
                 HRGWARHNCGHLEDASVICAEKSRCGGIITNSSGAIRNPPQNEMHDNITCVWEIKANA
                 SDHILLAFPHLLDCTNEYFEILDGPPSSVKSLGRTCSGFQHTYISSSSSMTLVYFRSF
                 NNLGKWLLTMYFLVLAEAVLQTPHLISQCPQRTTVTRSLSAGDWPELQLVGGSGRCSG
                 RVEILHQGAWGTVCDDLWDLNEAEVVCRQLGCGRAMSALGKAHFGPGSGDIFLDNLQC
                 AGVERYLGQCTHSGWSEHNHVSYSGIISTSEEVTPSPGCGGYLDTLEGSFTSPNYPKP
                 HPELAYCVWHIQVEKDYKIKLNFKEIEIDKQCKFDFLAIYDGPSTNSGLIGQVCGRVT
                 PTFESSSNSLTVVLSTDYANSYRGFSASYTSIYAENITASLTCSSDRMRVIISKSYLE
                 AFNSNGNNLQLKDPTCRPKLSNVVEFSVPLNGCGTIRQVEDQSITYTNIITFSASSTS
                 EVITRQKQLQIIVKCEMGHNSTVEIIYITEDDVIQSQNALGKYNTSMALFESNSFEKT
                 ILESPYYVDLNQTLFVQVSLHTSDPNLVVFLDTCRASPTSDFASPTYDLIKSGCSRDE
                 TCKVYPLFGHYGRFQFNAFKFLRSMSSVYLQCKVLICDSSDHQSRCNQGCVSRSKRDI
                 SSYKWKTDSIIGPIRLKRDRSASGNSGSQHETHAEETPNQPFNSVHLFSFMVLALNVV
                 TVATITVRHFVNQRADYKYQKLQNY
                 SEQ ID NO:137        744 bp
NOV40b,          GGTACCACTTGCTCTTCTGACAGGATGAGAGTTATTATAAGCAAATCCTACCTAGAGG
207728344 DNA    CTTTTAACTCTAATGGGAATAACTTGCAACTAAAAGACCCAACTTGCAGACCAAAATT
Sequence         ATCAAATGTTGTGGAATTTTCTGTCCCTCTTAATGGATGTGGTACAATCAGAAAGGTA
                 GAAGATCAGTCAATTACTTACACCAATATAATCGCCTTTTCTGCATCCTCAACTTCTG
                 AAGTGATCACCCGTCAGAAACAACTCCAGATTATTGTGAAGTGTGAAATGGGACATAA
                 TTCTACAGTGGAGATAATATACATAACAGAAGATGATGTAATACAAAGTCAAAATGCA
                 CTGGGCAAATATAACACCAGCATGGCTCTTTTTGAATCCAATTCATTTGAAAAGACTA
                 TACTTGAATCACCATATTATGTGGATTTGAACCAAACTCTTTTTGTTCAAGTTAGTCT
                 GCACACCTCAGATCCAAATTTGGTGGTGTTTCTTGATACCTGTAGAGCCTCTCCCACC
                 TCTGACTTTGCATCTCCAACCTACGACCTAATCAAGAGTGGATGTAGTCGAGATGAAA
                 CTTGTAAGGTGTATCCCTTATTTGGACACTATGGGAGATTCCAGTTTAATGCCTTTAA
                 ATTCTTGAGAAGTATGAGCTCTGTGTATCTGCAGTGTAAAGTTTTGATATGTGATAGC
                 AGTGACCACCAGTCTCGCTGCAATCAAGGTTGTGTCTCCAGACTCGAG
                 ORF Start: at 1      ORF Stop: end of sequence
                 SEQ ID NO:138        248 aa MW at 27830.1 kD
NOV40b,          GTTCSSDRMRVIISKSYLEAFNSNGNNLQLKDPTCRPKLSNVVEFSVPLNGCGTIRKV
207728344        EDQSITYTNIIAFSASSTSEVITRQKQLQIIVKCEMGHNSTVEIIYITEDDVIQSQNA
Protein Sequence LGKYNTSMALFESNSFEKTILESPYYVDLNQTLFVQVSLHTSDPNLVVFLDTCRASPT
                 SDFASPTYDLIKSGCSRDETCKVYPLFGHYGRFQFNAFKFLRSMSSVYLQCKVLICDS
                 SDHQSRCNQGCVSRLE
                 SEQ ID NO:139        744 bp
NOV40c,          GGTACCACTTGCTCTTCTGACAGGATGAGAGTTATTATAAGCAAATCCTACCTAGAGG
207728348 DNA    CTTTTAACTCTAATGGGAATAACTTGCAACTAAAAGACCCAACTTGCAGACCAAAATT
Sequence         ATCAAATGTTGTGGAATTTTCTGTCCCTCTTAATGGATGTGGTACAATCAGAAAGGTA
                 GAAGATCAGTCAATTACTTACACCAATATAATCACCTTTTCTGCATCCTCAACTTCTG
                 AAGTGATCACCCGTCAGAAACAACTCCAGATTATTCTGAAGTGTGAAATGGGACATAA
                 TTCTACAGTGGAGATAATATACATAACAGAAGATGATGTAATACAAAGTCAAAATGCA
                 CTGGGCAAATATAACACCAGCATGGCTCTTTTTGAATCCAATTCATTTGAAAAGACTA
                 TACTTGAAACACCATATTATGTGGATTTGAACCAAACTCTTTTTGTTCAAGTTAGTCT
                 GCACACCTCAGATCCAAATTTGGTGGTGTTTCTTGATACCTGTAGAGCCTCTCCCACC
                 TCTGACTTTGCATCTCCAACCTACGACCTAATCAAGAGTGGATGTAGTCGAGATGAAA
                 CTTGTAAGGTGTATCCCTTATTTGGACACTATGGGAGATTCCAGTTTAATGCCTTTAA
                 ATTCTTGAGAAGTATGAGCTCTGTGTATCTGCAGTGTAAAGTTTTGATATGTGATAGC
                 AGTGACCACCAGTCTCGCTGCAATCAAGGTTGTGTCTCCAGACTCGAG
                 ORF Start: at 1      ORF Stop: end of sequence
                 SEQ ID NO:140        248 aa MW at 27888.2 kD
NOV40c,          GTTCSSDRMRVIISKSYLEAFNSNGNNLQLKDPTCRPKLSNVVEFSVPLNGCGTIRKV
207728348        EDQSITYTNIITFSASSTSEVITRQKQLQIILKCEMGHNSTVEIIYITEDDVIQSQNA
Protein Sequence LGKYNTSMALFESNSFEKTILETPYYVDLNQTLFVQVSLHTSDPNLVVFLDTCRASPT
                 SDFASPTYDLIKSGCSRDETCKVYPLFGHYGRFQFNAFKFLRSMSSVYLQCKVLICDS
                 SDHQSRCNQGCVSRLE
                 SEQ ID NO:141        744 bp
NOV40d,          GGTACCACTTGCTCTTCTGACAGGATGAGAGTTATTATAAGCAAATCCTACCTAGAGG
207728354 DNA    CTTTTAACTCTAATGGGAATAACTTGCAACTAAAAGACCCAACTTGCAGACCAAAATT
Sequence         ATCAAATGTTGTGGAATTTTCTGTCCCTCTTAATGGATGTGGTACAATCAGAAAGGTA
                 GAAGATCAGTCAATTACTTACACCAATATAATCACCTTTTCTGCATCCTCAACTTCTG
                 AAGTGATCACCCGTCAGAAACAACTCCAGATTATTGTGAAGTGTGAAATGGGACATAA
                 TTCTACAGTGGAGATAATATACATAACAGAAGATGATGTAATACAAAGTCAAAATGCA
                 CTGGGCAAATATAACACCAGCATGGCTCTTTTTGAATCCAATTCATTTGAAAAGACTA
                 TACTTGAATCACCATATTATGTGGATTTGAACCAAACTCTTTTTGTTCAAGTTAGTCT
                 GCACACCTCAGATCCAAATTTGGTGGTGTTTCTTGATACCTGTAGAGCCTCTCCCACC
                 TCTGACTTTGCATCTCCAACCTACGACCTAATCAAGAGTGGATGTAGTCGAGATGAAA
                 CTTGTAAGGTGTATCCCTTATTTGGACACTATGGGAGATTCCAGTTTAATGCCTTTAA
                 ATTCTTGAGAAGTATGAGCTCTGTGTATCTGCAGTGTAAAGTTTTGATATGTGATAGC
                 AGTGACCACCAGTCTCGCTGCAATCAAGGTTGTGTCTCCAGACTCGAG
                 ORF Start: at 1      ORF Stop: end of sequence
                 SEQ ID NO:142        248 aa MW at 27860.2 kD
NOV40d,          GTTCSSDRMRVIISKSYLEAFNSNGNNLQLKDPTCRPKLSNVVEFSVPLNGCGTIRKV
207728354        EDQSITYTNIITFSASSTSEVITRQKQLQIIVKCEMGHNSTVEIIYITEDDVTQSQNA
Protein Sequence LGKYNTSMALFESNSFEKTILESPYYVDLNQTLFVQVSLHTSDPNLVVFLDTCRASPT
                 SDFASPTYDLIKSGCSRDETCKVYPLFGHYGRFQFNAFKFLRSMSSVYLQCKVLICDS
                 SDHQSRCNQGCVSRLE
                 SEQ ID NO:143        744 bp
NOV40e,          GGTACCACTTGCTCTTCTGACAGGATGAGAGTTATTATAAGCAAATCCTACCTAGAGG
207728365 DNA    CTTTTAACTCTAATGGGAATAACTTGCAACTAAAAGACCCAACTTGCAGACCAAAATT
Sequence         ATCAAATGTTGTGGAATTTTCTGTCCCTCTTAATGGATGTGGTACAATCAGAAAGGTA
                 GAAGATCAGTCAATTACTTACACCAATATAATCACCCTTTCTGCATCCTCAACTTCTG
                 AAGTGATCACCCGTCAGAAACAACTCCAGATTATTGTGAAGTGTGAAATGGGACATAA
                 TTCTACAGTGGAGATAATATACATAACAGAAGATGATGTAATACAAAGTCAAAATGCA
                 CTGGGCAAATATAACACCAGCATGGCTCTTTTTGAATCCAATTCATTTGAAAAGACTA
                 TACTTGAATCACCATATTATGTGGATTTGAACCAAACTCTTTTTGTTCAAGTTAGTCT
                 GCACACCTCAGATCCAAATTTGGTGGTGTTTCTTGATACCTGTAGAGCCTCTCCCACC
                 TCTGACTTTGCATCTCCAACCTACGACCTAATCAAGAGTGGATGTAGTCGAGATGAAA
                 CTTGTAAGGTGTATCCCTTATTTGGACACTATGGGAGATTCCAGTTTAATGCCTTTAA
                 ATTCTTGAGAAGTATGAGCTCTGTGTATCTGCAGTGTAAAGTTTTGATATGTGATAGC
                 AGTGACCACCAGTCTCGCTGCAATCAAGGTTGTGTCTCCAGACTCGAG
                 ORF Start: at 1      ORF Stop: end of sequence
                 SEQ ID NO:144        248 aa MW at 27826.1 kD
NOV40e,          GTTCSSDRMRVIISKSYLEAFNSNGNNLQLKDPTCRPKLSNVVEFSVPLNGCGTIRKV
207728365        EDQSITYTNIITLSASSTSEVITRQKQLQIIVKCEMGHNSTVETIYITEDDVIQSQNA
Protein Sequence LGKYNTSMALFESNSFEKTILESPYYVDLNQTLFVQVSLHTSDPNLVVFLDTCRASPT
                 SDFASPTYDLIKSGCSRDETCKVYPLFGHYGRFQFNAFKFLRSMSSVYLQCKVLICDS
                 SDHQSRCNQGCVSRLE

[0515] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 40B.

TABLE 40B
Comparison of NOV40a against NOV40b through NOV40e.
	NOV40a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV40b	680 . . . 923	242/244 (99%)
	3 . . . 246	243/244 (99%)
NOV40c	680 . . . 923	241/244 (98%)
	3 . . . 246	244/244 (99%)
NOV40d	680 . . . 923	243/244 (99%)
	3 . . . 246	244/244 (99%)
NOV40e	680 . . . 923	242/244 (99%)
	3 . . . 246	243/244 (99%)

[0516] Further analysis of the NOV40a protein yielded the following properties shown in Table 40C.

TABLE 40C
Protein Sequence Properties NOV40a
PSort     0.7000 probability located in plasma membrane;
analysis: 0.5843 probability located in
          mitochondrial inner membrane;
          0.3000 probability located in microbody
          (peroxisome); 0.2000 probability located
          in endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0517] A search of the NOV40a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 40D.

TABLE 40D
Geneseq Results for NOV40a
		NOV40a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB80245	Human PRO257 protein - Homo	559 . . . 1011	449/456 (98%)	0.0
	sapiens, 607 aa. [WO200104311-	152 . . . 607	450/456 (98%)
	A1, 18-JAN-2001]
AAU12343	Human PRO257 polypeptide	559 . . . 1011	449/456 (98%)	0.0
	sequence - Homo sapiens, 607 aa.	152 . . . 607	450/456 (98%)
	[WO200140466-A2, 07-JUN-2001]
AAB07456	Protein encoded by a novel gene	559 . . . 1011	449/456 (98%)	0.0
	associated with insulin synthesis -	130 . . . 585	450/456 (98%)
	Homo sapiens, 585 aa.
	[WO200040722-A2, 13-JUL-2000]
AAY13377	Amino acid sequence of protein	559 . . . 1011	449/456 (98%)	0.0
	PRO257 - Homo sapiens, 607 aa.	152 . . . 607	450/456 (98%)
	[WO9914328-A2, 25-MAR-1999]
AAY25323	Human pancreatic PA153 consensus	559 . . . 1011	449/456 (98%)	0.0
	protein - Homo sapiens, 607 aa.	152 . . . 607	450/456 (98%)
	[WO9931274-A2, 24-JUN-1999]

[0518] In a BLAST search of public sequence databases, the NOV40a protein was found to have homology to the proteins shown in the BLASTP data in Table 40E.

TABLE 40E
Public BLASTP Results for NOV40a
		NOV40a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96DU4	DMBT1/8KB.2 PROTEIN	8 . . . 945	435/1028 (42%)	0.0
	PRECURSOR - Homo sapiens	1406 . . . 2403	605/1028 (58%)
	(Human), 2413 aa.
Q9UGM3	DMBT1 PROTOTYPE	8 . . . 945	435/1028 (42%)	0.0
	PRECURSOR - Homo sapiens	1419 . . . 2416	605/1028 (58%)
	(Human), 2426 aa.
Q9Y4V9	DMBT1/6KB.1 PROTEIN	8 . . . 945	435/1028 (42%)	0.0
	PRECURSOR - Homo sapiens	778 . . . 1775	605/1028 (58%)
	(Human), 1785 aa.
Q9UKJ4	GP-340 VARIANT PROTEIN -	8 . . . 945	435/1028 (42%)	0.0
	Homo sapiens (Human), 2413 aa.	1406 . . . 2403	605/1028 (58%)
Q9Y211	DMBT1 - Homo sapiens	8 . . . 945	435/1028 (42%)	0.0
	(Human), 1785 aa.	778 . . . 1775	605/1028 (58%)

[0519] PFam analysis predicts that the NOV40a protein contains the domains shown in the Table 40F.

TABLE 40F
Domain Analysis of NOV40a
		Identities/
		Similarities
	NOV40a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
SRCR	1 . . . 82	37/114 (32%)	2.2e−10
		62/114 (54%)
SRCR	104 . . . 201	48/114 (42%)	2.4e−34
		78/114 (68%)
SRCR	217 . . . 310	43/113 (38%)	3.2e−24
		72/113 (64%)
CUB	315 . . . 416	38/118 (32%)	2.6e−10
		72/118 (61%)
SRCR	456 . . . 551	47/114 (41%)	1.9e−28
		78/114 (68%)
CUB	561 . . . 667	38/117 (32%)	4.9e−35
		83/117 (71%)
zona_pellucida	680 . . . 923	78/286 (27%)	4.1e−40
		184/286 (64%)

Example 41

[0520] The NOV41 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 41A.

TABLE 41A
NOV41 Sequence Analysis
                 SEQ ID NO:145       4011 bp
NOV41a,          ATGCCTCTGTCCAGCCACCTGCTGCCCGCCTTGGTCCTGTTCCTGGGCCACCTGGCTG
CG99598-01       TCAACCTCCCAGCAGCAGGGTCCTCAGGCTGGGCCTGGGTCCCCAACCACTGCAGGAG
DNA Sequence     CCCTGGCCAGGCCGTGTGCAACTTCGTGTGTGACTGCAGGGACTGCTCAGATGAGGCC
                 CAGTGTGGTTACCACGGGGCCTCGCCCACCCTGGGCGCCCCCTTCGCCTGTGACTTCG
                 AGCAGGACCCCTGCGGCTGGCGGGACATTAGTACCTCAGGCTACAGCTGGCTCCGAGA
                 CAGGGCAGGGGCCGCACTGGAGGGTCCTGGGCCTCACTCAGACCACACACTGGGCACC
                 GACTTGGGCTGGTACATGGCCGTTGGAACCCACCGAGGGAAAGAGGCATCCACCGCAG
                 CCCTGCGCTCGCCAACCCTGCGAGAGGCAGCCTCCTCTTGCAAGCTGAGGCTCTGGTA
                 CCACGCGGCCTCTGGAGATGTGGCTGAACTGCGGGTGGAGCTGACCCATGGCGCAGAG
                 ACCCTGACCCTGTGGCAGAGCACAGGGCCCTGGGGCCCTGGCTGGCAGGAGTTGGCAG
                 TGACCACAGGCCGCATCCGGGGTGACTTCCGAGTGACCTTCTCTGCCACCCGAAATGC
                 CACCCACAGGGGCGCTGTGGCTCTAGATGACCTAGAGTTCTGGGACTGTGGTCTGCCC
                 ACCCCCCAGGCCAACTGTCCCCCGGGACACCACCACTGCCAGAACAAGGTCTGCGTGG
                 AGCCCCAGCAGCTGTGCGACGGGGAAGACAACTGCGGGGACCTGTCTGATGAGAACCC
                 ACTCACCTGTGGCCGCCACATAGCCACCGACTTTGAGACAGGCCTGGGCCCATGGAAC
                 CGCTCGGAAGGCTGGTCCCGGAACCACCGCGCTGGTGGTCCTGAGCGCCCCTCCTGGC
                 CACGCCGTGACCACAGCCGGAACAGTGCACAGGGCTCCTTCCTGGTCTCCGTGGCCGA
                 GCCTGGCACCCCTGCTATACTCTCCAGCCCCGAATTCCAAGCCTCAGQCACCTCCAAC
                 TGCTCCGCCCCCAGCCAGCTCTTGGTTCCACAGCTGGTCTTCTATCAGTACCTGAGTG
                 GGTCTGAGGCTGGCTGCCTCCAGCTGTTCCTGCAGACTCTGGGGCCCGGCGCCCCCCG
                 GGCCCCCGTCCTGCTGCGGAGGCGCCGAGGGGAGCTGGGGACCGCCTGGGTCCGAGAC
                 CGTGTTGACATCCAGAGCGCCTACCCCTTCCAGATCCTCCTGGCCGGGCAGACAGGCC
                 CGGGGGGCGTCGTGGGTCTGGACGACCTCATCCTGTCTGACCACTGCAGACCAGTCTC
                 GGAGGTGTCCACCCTGCAGCCGCTGCCTCCTGGGCCCCGGGCCCCAGCCCCCCAGCCC
                 CTGCCGCCCAGCTCGCGGCTCCAGGATTCCTGCAAGCAGGGGCATCTTGCCTGCGGGG
                 ACCTGTGTGTGCCCCCGGAACAACTGTGTGACTTCGAGGAGCAGTGCGCAGGGGGCGA
                 GGACGAGCAGGCCTGTGGTAAAGGGGCTCAACCTCCTGCAGACCTCCTGCTGCGGAGC
                 CAAGGGGGCACCACAGACTTTGAGTCCCCCGAGGCTGGGGGCTGGGAGGACGCCAGCG
                 TGGGGCGGCTGCAGTGGCGGCGTGTCTCAGCCCAGGAGAGCCAGGGGTCCAGTGCAGC
                 TGCTGCTGGCTTCCTGGCACTAGTTGTGGTGGACAACGGCTCCCGGGAGCTGGCATGG
                 CAGGCCCTGAGCAGCAGTGCAGGCATCTGGAAGGTGGACAAGGTCCTTCTAGGGGCCC
                 GCCGCCGGCCCTTCCGGCTGGAGTTTGTCGGTTTGGTGGACTTGGATGGCCCTGACCA
                 GCAGGGAGCTGGGGTGGACAACGTGACCCTGAGGGACTGTAGCCCCACAGTGACCACC
                 GAGAGAGACAGAGAGGTCTCCTGTAACTTTGAGCGGGACACATGCAGCTGGTACCCAG
                 GCCACCTCTCAGACACACACTGGCGCTGGGTGGAGAGCCGCGGCCCTGACCACGACCA
                 CACCACAGGCCAAGGCCACTTTGTGCTCCTGGACCCCACAGACCCCCTGGCCTGGGGC
                 CACAGTGCCCACCTGCTCTCCAGGCCCCAGGTGCCAGCAGCACCCACGGAGTGTCTCA
                 GCTTCTGGTACCACCTCCATGGGCCCCAGATTGGGACTCTGCGCCTAGCCATGAGACG
                 GGAAGGGGAGGAGACACACCTGTGGTCGCGGTCAGGCACCCAGGGCAACCGCTGGCAC
                 GAGGCCTGGGCCACCCTTTCCCACCAGCCTGGCTCCCATGCCCAGTACCAGCTGCTGT
                 TCGAGGGCCTCCGGGACGGATACCACGGCACCATGGCGCTGGACGATGTGGCCGTGCG
                 GCCGGGCCCCTGCTGGGCCCCTAATTACTGCTCCTTTGAGGACTCAGACTGCGGCTTC
                 TCCCCTGGAGGCCAAGGTCTCTGGAGGCGGCAGGCCAATGCCTCGGGCCATGCTGCCT
                 GGGGCCCCCCAACAGACCATACCACTGAGACAGCCCAAGGGCACTACATGGTGGTGGA
                 CACAAGCCCAGACGCACTACCCCGGGGCCAGACGGCCTCCCTGACCTCCAAGGAGCAC
                 AGGCCCCTGGCCCAGCCTGCTTGTCTGACCTTCTGGTACCACGGGAGCCTCCGCAGCC
                 CAGGCACCCTGCGGGTCTACCTGGAGGAGCGCGGGAGGCACCAGGTGCTCAGCCTCAG
                 TGCCCACGGCGGGCTTGCCTGGCGCCTGGGCAGCATGGACGTGCAGGCCGAGCGAGCC
                 TGGAGGGTGGTGTTTGAGGCAGTGGCCGCAGGCGTGGCACACTCCTACGTGGCTCTGG
                 ATGATCTGCTCCTCCAGGACGGGCCCTGCCCTCAGCCAGGTTCCTGTGATTTTGAGTC
                 TGGCCTGTGTGGCTGGAGCCACCTGGCCTGGCCCGGCCTGGGCGGATACAGCTGGGAC
                 TGGGGCGGGGGAGCCACCCCCTCTCGTTACCCCCAGCCCCCTGTGGACCACACCCTGG
                 GCACAGAGGCAGGCCACTTTGCCTTCTTTGAAACTGGCGTGCTGGGCCCCGGGGGCCG
                 GGCCGCCTGGCTGCGCAGCGAGCCTCTGCCGGCCACCCCAGCCTCCTGCCTCCGCTTC
                 TGGTACCACATGGGTTTTCCTGAGCACTTCTACAAGGGGGAGCTGAAGGTACTGCTGC
                 ACAGTGCTCAGGGCCAGCTGGCTGTGTGGGGCGCAGGCGGGCATCGGCGGCACCAGTG
                 GCTGGAGGCCCAGGTGGAGGTAGCCAGTGCCAAGGAGTTCCAGATCGTGTTTGAAGCC
                 ACTCTGGGCGGCCAGCCAGCCCTGGGGCCCATTGCCCTGGATGACGTGGAGTATCTGG
                 CTGGGCAGCATTGCCAGCAGCCTGCCCCCAGCCCGGGGAACACAGCCGCACCCGGGTC
                 TGTGCCAGCTGTGGTTGGCAGTGCCCTCCTATTGCTCATGCTCCTGGTGCTGCTGGGA
                 CTTGGGGGACGGCGCTGGCTGCAGAAGAAGGGGAGCTGCCCCTTCCAGAGCAACACAG
                 AGGCCACAGCCCCTGGCTTTGACAACATCCTTTTCAATGCGGAGCCATGCGGTGTTGG
                 AGGGCACAGCACAGCACCCTTGCCAGCCGCTAGGCTCCCATCCGCCCTGGGGACTAAG
                 TCCCAGCGGAGGGCGGCAGTTGGGCACGGCTACCGCCGTCCCTCGTCTTCAGGTGCCG
                 TGGGGCTGACCAGTGCCCACCAACTGTCCACGCAGATGGGCGAAGAGGAAATGGCCCT
                 GCAGAGACCTTCAGAGCTCCCCCCGGCAGCCCACTCCCGGGCATCAGTCATGAAAATT
                 CACCAGCTTTCCCCACAACTAGGGGCCTGGGAGCTGAGAGCAGGACCGGACAATCTGG
                 CCCCAGCGCCAAGGGCAGGAACTTTTCCCAGCTTCTCTTCAGAGCTGCATCAAAGAAA
                 GCAGCGCCCAGTGACACCGCTCCTCTTCCTTCCACGCCTCAGGCCTCCACCCCTCACC
                 CTTGTATAA
                 ORF Start: ATG at 1 ORF Stop: TAA at 4009
                 SEQ ID NO:146       1336 aa MW at 144032.7 kD
NOV41a,          MPLSSHLLPALVLFLGHLAVNLPAAGSSGWAWVPNHCRSPGQAVCNFVCDCRDCSDEA
CG99598-01       QCGYHGASPTLGAPFACDFEQDPCGWRDISTSGYSWLRDRAGAALEGPGPHSDHTLGT
Protein Sequence DLGWYMAVGTHRGKEASTAALRSPTLREAASSCKLRLWYHAASGDVAELRVELTHGAE
                 TLTLWQSTGPWGPGWQELAVTTGRIRGDFRVTFSATRNATHRGAVALDDLEFWDCGLP
                 TPQANCPPGHHHCQNKVCVEPQQLCDGEDNCGDLSDENPLTCGRHIATDFETGLGPWN
                 RSEGWSRNHRAGGPERPSWPRRDHSRNSAQGSFLVSVAEPGTPAILSSPEFQASGTSN
                 CSAPSQLLVPQLVFYQYLSGSEAGCLQLFLQTLGPGAPRAPVLLRRRRGELGTAWVRD
                 RVDIQSAYPFQILLAGQTGPGGVVGLDDLILSDHCRPVSEVSTLQPLPPGPRAPAPQP
                 LPPSSRLQDSCKQGHLACGDLCVPPEQLCDFEEQCAGGEDEQACGKGAQFPADLLLRS
                 QGGTTDFESPEAGGWEDASVGRLQWRRVSAQESQGSSAAAAGFLALVVVDNGSRELAW
                 QALSSSAGIWKVDKVLLGARRRPFRLEFVGLVDLDGPDQQGAGVDNVTLRDCSPTVTT
                 ERDREVSCNFERDTCSWYPGHLSDTHWRWVESRGPDHDHTTGQGHFVLLDPTDPLAWG
                 HSAHLLSRPQVPAAPTECLSFWYHLHGPQIGTLRLAMRREGEETHLWSRSGTQGNRWH
                 EAWATLSHQPGSHAQYQLLFEGLRDGYHGTMALDDVAVRPGPCWAPNYCSFEDSDCGF
                 SPGGQGLWRRQANASGHAAWGPPTDHTTETAQGHYMVVDTSPDALPRGQTASLTSKEH
                 RPLAQPACLTFWYHGSLRSPGTLRVYLEERGRHQVLSLSAHGGLAWRLGSMDVQAERA
                 WRVVFEAVAAGVAHSYVALDDLLLQDGPCPQPGSCDFESGLCGWSHLAWPGLGGYSWD
                 WGGGATPSRYPQPPVDHTLGTEAGHFAFFETGVLGPGGPAAWLRSEPLPATPASCLRF
                 WYHMGFPEHFYKGELKVLLHSAQGQLAVWGAGGHRRHQWLEAQVEVASAKEFQIVFEA
                 TLGGQPALGPIALDDVEYLAGQHCQQPAPSPGNTAAPGSVPAVVGSALLLLMLLVLLG
                 LGGRRWLQKKGSCPFQSNTEATAPGFDNILFNAEPCGVGGHSTAPLPAARLPSALGTK
                 SQRPAAVGHGYRRPSSSGAVGLTSAHQLSTQMGEEEMALQRPSELPPAAHSRASVMKI
                 HQLSPQLGAWELRAGPDNLAPAPRAGTFPSFSSELHQRKQRPVTPLLFLPRLRPPPLT
                 LV

[0521] Further analysis of the NOV41a protein yielded the following properties shown in Table 41B.

TABLE 41B
Protein Sequence Properties NOV41a
PSort     0.4600 probability located in plasma membrane;
analysis: 0.2464 probability located in
          microbody (peroxisome); 0.1000 probability
          located in endoplasmic reticulum
          (membrane); 0.1000 probability located in
          endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 20 and 21
analysis:

[0522] A search of the NOV41a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 41C.

TABLE 41C
Geneseq Results for NOV41a
		NOV41a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAE17494	Human secretion and trafficking	1 . . . 1194	1159/1238 (93%)	0.0
	protein-3 (SAT-3) - Homo sapiens,	1 . . . 1205	1160/1238 (93%)
	1217 aa. [WO200202610-A2, 10-JAN-2002]
AAU29282	Human PRO polypeptide sequence	1 . . . 1194	1093/1195 (91%)	0.0
	#259 - Homo sapiens, 1137 aa.	1 . . . 1125	1099/1195 (91%)
	[WO200168848-A2, 20-SEP-2001]
AAB42780	Human ORFX ORF2544	161 . . . 620	372/475 (78%)	0.0
	polypeptide sequence SEQ ID	45 . . . 453	379/475 (79%)
	NO: 5088 - Homo sapiens, 465 aa.
	[WO200058473-A2, 05-OCT-2000]
AAB01432	Human TANGO 239 (form 2) -	574 . . . 957	110/406 (27%)	4e−29
	Homo sapiens, 686 aa.	270 . . . 664	178/406 (43%)
	[WO200039284-A1, 06-JUL-2000]
ABB53298	Human polypeptide #38 - Homo	574 . . . 957	109/406 (26%)	8e−28
	sapiens, 686 aa. [WO200181363-	270 . . . 664	176/406 (42%)
	A1, 01-NOV-2001]

[0523] In a BLAST search of public sequence databases, the NOV41a protein was found to have homology to the proteins shown in the BLASTP data in Table 41D.

TABLE 41D
Public BLASTP Results for NOV41a
		NOV41a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q63191	Apical endosomal glycoprotein	1 . . . 1194	848/1245 (68%)	0.0
	precursor - Rattus norvegicus	1 . . . 1204	944/1245 (75%)
	(Rat), 1216 aa.
Q91641	Thyroid hormone-induced protein	573 . . . 957	118/415 (28%)	1e−28
	B precursor - Xenopus laevis	270 . . . 667	187/415 (44%)
	(African clawed frog), 688 aa.
O88799	Zonadhesin precursor - Mus	631 . . . 1109	141/518 (27%)	3e−27
	musculus (Mouse), 5376 aa.	30 . . . 525	221/518 (42%)
Q99ND0	ZAN (ZONADHESIN) - Mus	631 . . . 1109	141/518 (27%)	6e−27
	musculus (Mouse), 5374 aa.	30 . . . 525	221/518 (42%)
Q9BZ83	ZONADHESIN VARIANT 6 -	636 . . . 1109	143/522 (27%)	8e−20
	Homo sapiens (Human), 2721 aa.	29 . . . 519	209/522 (39%)

[0524] PFam analysis predicts that the NOV41a protein contains the domains shown in the Table 41E.

TABLE 41E
Domain Analysis of NOV41a
		Identities/
		Similarities
	NOV41a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
MAM	75 . . . 231	57/174 (33%)	1.4e−44
		122/174 (70%)
ldl_recept_a	236 . . . 276	13/43 (30%)	3.3e−09
		29/43 (67%)
MAM	280 . . . 443	48/188 (26%)	7.2e−22
		122/188 (65%)
ldl_recept_a	473 . . . 510	12/43 (28%)	0.2
		26/43 (60%)
MAM	493 . . . 634	33/174 (19%)	0.0004
		86/174 (49%)
MAM	646 . . . 799	68/173 (39%)	6.7e−54
		132/173 (76%)
MAM	803 . . . 959	67/173 (39%)	2.5e−47
		119/173 (69%)
MAM	963 . . . 1128	62/176 (35%)	6.4e−56
		137/176 (78%)

Example B: Sequencing Methodology and Identification of NOVX Clones

[0525] 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.

[0526] 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.

[0527] 3. PathCalling™ Technology:

[0528] The NOVX nucleic acid sequences are derived by laboratory screening of cDNA library by the two-hybrid approach. cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, are sequenced. In silico prediction was based on sequences available in CuraGen Corporation's proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.

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

[0530] cDNA libraries were derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then directionally cloned into the appropriate two-hybrid vector (Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, Calif.) were then transferred from E.coli into a CuraGen Corporation proprietary yeast strain (disclosed in U.S. Pat. Nos. 6,057,101 and 6,083,693, incorporated herein by reference in their entireties).

[0531] Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corportion proprietary library of human sequences was used to screen multiple Gal4-AD fusion cDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Gal4-AD fusion contains an individual cDNA. Each sample was amplified using the polymerase chain reaction (PCR) using non-specific primers at the cDNA insert boundaries. Such PCR product was sequenced; sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.

[0532] Physical clone: the cDNA fragment derived by the screening procedure, covering the entire open reading frame is, as a recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library. The recombinant plasmid is inserted into the host and selected by the yeast hybrid diploid generated during the screening procedure by the mating of both CuraGen Corporation proprietary yeast strains N106′ and YULH (U.S. Pat. Nos. 6,057,101 and 6,083,693).

[0533] 4. RACE: Techniques based on the polymerase chain reaction such as rapid amplification of cDNA ends (RACE), were used to isolate or complete the predicted sequence of the cDNA of the invention. Usually multiple clones were sequenced from one or more human samples to derive the sequences for fragments. Various human tissue samples from different donors were used for the RACE reaction. The sequences derived from these procedures were included in the SeqCalling Assembly process described in preceding paragraphs.

[0534] 5. Exon Linking: The NOVX target sequences identified in the present invention were subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the predicted exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain—amygdala, brain—cerebellum, brain—hippocampus, brain—substantia nigra, brain—thalamus, brain—whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma—Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus. Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation's database and with public ESTs. Fragments and ESTs were included as components for an assembly when the extent of their identity with another component of the assembly was at least 95% over 50 bp. In addition, sequence traces were evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported herein.

[0535] 6. Physical Clone: Exons were predicted by homology and the intron/exon boundaries were determined using standard genetic rules. Exons were further selected and refined by means of similarity determination using multiple BLAST (for example, tBlastN, BlastX, and BlastN) searches, and, in some instances, GeneScan and Grail. Expressed sequences from both public and proprietary databases were also added when available to further define and complete the gene sequence. The DNA sequence was then manually corrected for apparent inconsistencies thereby obtaining the sequences encoding the full-length protein.

[0536] The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening purposes.

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

[0537] The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoimmune diseases), Panel CNSD.01 (containing central nervous system samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer's diseased brains).

[0538] 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.

[0539] 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.

[0540] In other cases, non-normalized RNA samples were converted to single strand cDNA (sscDNA) using Superscript II (Invitrogen Corporation; Catalog No. 18064-147) and random hexamers according to the manufacturer's instructions. Reactions containing up to 10 μg of total RNA were performed in a volume of 20 μl and incubated for 60 minutes at 42° C. This reaction can be scaled up to 50 μg of total RNA in a final volume of 100 μl. sscDNA samples are then normalized to reference nucleic acids as described previously, using 1×TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions.

[0541] Probes and primers were designed for each assay according to Applied Biosystems Primer Express Software package (version I for Apple Computer's Macintosh Power PC) or a similar algorithm using the target sequence as input. Default settings were used for reaction conditions and the following parameters were set before selecting primers: primer concentration=250 nM, primer melting temperature (Tm) range=58°-60° C., primer optimal Tm=59° C., maximum primer difference=2° C., probe does not have 5′G, probe Tm must be 10° C. greater than primer Tm, amplicon size 75 bp to 100 bp. The probes and primers selected (see below) were synthesized by Synthegen (Houston, Tex., USA). Probes were double purified by HPLC to remove uncoupled dye and evaluated by mass spectroscopy to verify coupling of reporter and quencher dyes to the 5′ and 3′ ends of the probe, respectively. Their final concentrations were: forward and reverse primers, 900 nM each, and probe, 200 nM.

[0542] 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.

[0543] 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.

[0544] Panels 1, 1.1, 1.2, and 1.3D

[0545] 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.

[0546] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:

[0547] ca.=carcinoma,

[0548] *=established from metastasis,

[0549] met=metastasis,

[0550] s cell var=small cell variant,

[0551] non-s=non-sm=non-small,

[0552] squam=squamous,

[0553] pl. eff=pl effusion=pleural effusion,

[0554] glio=glioma,

[0555] astro=astrocytoma, and

[0556] neuro=neuroblastoma.

[0557] General_Screening_Panel_v1.4

[0558] The plates for Panel 1.4 include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panel 1.4 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 Panel 1.4 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 Panel 1.4 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.

[0559] Panels 2D and 2.2

[0560] The plates for Panels 2D and 2.2 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). 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 or CHTN). This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, Calif.), Research Genetics, and Invitrogen. General oncology screening panel_v—2.4 is an updated version of Panel 2D.

[0561] Panel 3D

[0562] The plates of Panel 3D are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines, 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma of the tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D and 1.3D are of the most common cell lines used in the scientific literature. Oncology_cell_line_screening_panel_v3.2 is an updated version of Panel 3. The Cell Lines in panel 3D, 1.3D and oncology_cell_line_screening_panel_v3.2 are of the most common cell lines used in the scientific literature.

[0563] Panels 4D, 4R, and 4.1D

[0564] 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.).

[0565] Astrocytes, lung fibroblasts, dermal fibroblasts, coronary artery smooth muscle cells, small airway epithelium, bronchial epithelium, microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells, human umbilical vein endothelial cells were all purchased from Clonetics (Walkersville, Md.) and grown in the media supplied for these cell types by Clonetics. These primary cell types were activated with various cytokines or combinations of cytokines for 6 and/or 12-14 hours, as indicated. The following cytokines were used; IL-1 beta at approximately 1-5 ng/ml, TNF alpha at approximately 5-10 ng/ml, IFN gamma at approximately 20-50 ng/ml, IL-4 at approximately 5-10 ng/ml, IL-9 at approximately 5-10 ng/ml, IL-13 at approximately 5-10 ng/ml. Endothelial cells were sometimes starved for various times by culture in the basal media from Clonetics with 0.1% serum.

[0566] 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 g/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.

[0567] Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer's instructions. Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, Utah), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and 10% AB Human Serum or MCSF at approximately 50 ng/ml. Monocytes, macrophages and dendritic cells were stimulated for 6 and 12-14 hours with lipopolysaccharide (LPS) at 100 ng/ml. Dendritic cells were also stimulated with anti-CD40 monoclonal antibody (Pharmingen) at 10 μg/ml for 6 and 12-14 hours.

[0568] 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.

[0569] 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.

[0570] To prepare the primary and secondary Th1/Th2 and Tr1 cells, six-well Falcon plates were coated overnight with 10 μg/ml anti-CD28 (Pharmingen) and 2 μg/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic Systems, German Town, Md.) were cultured at 105-106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4 ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 μg/ml) were used to direct to Th1, while IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct to Tr1. After 4-5 days, the activated Th1, Th2 and Tr1 lymphocytes were washed once in DMEM and expanded for 4-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (1 ng/ml). Following this, the activated Th1, Th2 and Tr1 lymphocytes were re-stimulated for 5 days with anti-CD28/OKT3 and cytokines as described above, but with the addition of anti-CD95L (1 μg/ml) to prevent apoptosis. After 4-5 days, the Th1, Th2 and Tr1 lymphocytes were washed and then expanded again with IL-2 for 4-7 days. Activated Th1 and Th2 lymphocytes were maintained in this way for a maximum of three cycles. RNA was prepared from primary and secondary Th1, Th2 and Tr1 after 6 and 24 hours following the second and third activations with plate bound anti-CD3 and anti-CD28 mAbs and 4 days into the second and third expansion cultures in Interleukin 2.

[0571] The following leukocyte cells lines were obtained from the ATCC: Ramos, EOL-1, KU-812. EOL cells were further differentiated by culture in 0.1 mM dbcAMP at 5×105 cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×105 cells/ml. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco). CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.

[0572] 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.

[0573] AI_Comprehensive Panel_v1.0

[0574] 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.

[0575] 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.

[0576] 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.

[0577] 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.

[0578] 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-1 anti-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.

[0579] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:

[0580] AI=Autoimmunity

[0581] Syn=Synovial

[0582] Normal=No apparent disease

[0583] Rep22/Rep20=individual patients

[0584] RA=Rheumatoid arthritis

[0585] Backus=From Backus Hospital

[0586] OA=Osteoarthritis

[0587] (SS)(BA)(MF)=Individual patients

[0588] Adj=Adjacent tissue

[0589] Match control=adjacent tissues

[0590] -M=Male

[0591] -F=Female

[0592] COPD=Chronic obstructive pulmonary disease

[0593] Panels 5D and 5I

[0594] 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.

[0595] In the Gestational Diabetes study subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (<1 cc) of the exposed metabolic tissues during the closure of each surgical level. The biopsy material was rinsed in sterile saline, blotted and fast frozen within 5 minutes from the time of removal. The tissue was then flash frozen in liquid nitrogen and stored, individually, in sterile screw-top tubes and kept on dry ice for shipment to or to be picked up by CuraGen. The metabolic tissues of interest include uterine wall (smooth muscle), visceral adipose, skeletal muscle (rectus) and subcutaneous adipose. Patient descriptions are as follows:

[0596] Patient 2 Diabetic Hispanic, overweight, not on insulin

[0597] Patient 7-9 Nondiabetic Caucasian and obese (BMI>30)

[0598] Patient 10 Diabetic Hispanic, overweight, on insulin

[0599] Patient 11 Nondiabetic African American and overweight

[0600] Patient 12 Diabetic Hispanic on insulin

[0601] Adipocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr. 2, 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:

[0602] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0603] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated

[0604] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0605] 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.

[0606] 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.

[0607] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:

[0608] GO Adipose=Greater Omentum Adipose

[0609] SK=Skeletal Muscle

[0610] UT=Uterus

[0611] PL=Placenta

[0612] AD=Adipose Differentiated

[0613] AM=Adipose Midway Differentiated

[0614] U=Undifferentiated Stem Cells

[0615] Panel CNSD.01

[0616] 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.

[0617] 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.

[0618] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:

[0619] PSP=Progressive supranuclear palsy

[0620] Sub Nigra=Substantia nigra

[0621] Glob Palladus=Globus palladus

[0622] Temp Pole=Temporal pole

[0623] Cing Gyr=Cingulate gyrus

[0624] BA 4=Brodman Area 4

[0625] Panel CNS_Neurodegeneration_V1.0

[0626] 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.

[0627] 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.

[0628] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:

[0629] AD=Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy

[0630] Control=Control brains; patient not demented, showing no neuropathology

[0631] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology

[0632] SupTemporal Ctx=Superior Temporal Cortex

[0633] Inf Temporal Ctx=Inferior Temporal Cortex

[0634] A. CG100689-01: LRR Protein

[0635] Expression of gene CG100689-01 was assessed using the primer-probe set Ag4186, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB and AC.

TABLE AA
Probe Name Ag4186
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ccagagtgttctgctctttgag-3′	22	1941	147
Probe	TET-5′-tgctcttttatcagccagacttgaaa-3′-TAMRA	26	1964	148
Reverse	5′-gagagtttcgtgagggtgaag-3′	21	1998	149

[0636]

TABLE AB
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4186, Run		Ag4186, Run
Tissue Name	221154078	Tissue Name	221154078
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	0.0
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	2.3	Gastric ca. KATO III	15.9
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	12.3
Squamous Cell	2.2	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	100.0	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	28.3
PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	3.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	30.1	Colon Pool	1.7
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	1.7
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	1.7	Heart Pool	1.3
Breast ca. MDA-MB-	0.0	Lymph Node Pool	3.2
231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	12.2
Breast Pool	0.0	Thymus pool	0.0
Trachea	1.7	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	2.6	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-	0.0
		75
Lung ca. NCI-H146	34.6	CNS cancer (glio) SNB-19	1.6
Lung ca. SHP-77	10.5	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	5.5
Lung ca. NCI-H526	0.0	Brain (cerebellum)	4.8
Lung ca. NCI-H23	2.4	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	9.4
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	4.4
Fetal Liver	1.7	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	2.7
Kidney Pool	2.6	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	2.4

[0637]

TABLE AC
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4186, Run		Ag4186, Run
Tissue Name	182086756	Tissue Name	182086756
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC	0.0
		none
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNFalpha + IL-1 beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNFalpha + IL-1beta
Primary Th1 rest	0.5	Bronchial epithelium	0.0
		TNFalpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	0.0
		none
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNFalpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.5	Coronery artery SMC	0.0
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNFalpha +	0.0
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.4
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells	0.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1	0.0
		beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha +	0.4
		IL-1 beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.4	Lung fibroblast IL-13	0.0
Ramos (B cell)	0.5	Lung fibroblast IFN	1.1
ionomycin		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L	16.5	Dermal fibroblast	0.0
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	1.0	Dermal fibroblast	0.0
		CCD1070 IL-1 beta
EOL-1 dbcAMP	3.8	Dermal fibroblast IFN	3.2
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	1.0
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	2.3
Monocytes LPS	0.0	Colon	1.4
Macrophages rest	0.4	Lung	1.6
Macrophages LPS	0.0	Thymus	19.6
HUVEC none	0.6	Kidney	100.0
HUVEC starved	0.0

[0638] General_screening_panel_v1.4 Summary: Ag4186 Expression of this gene is restricted to the testis (CT=33.7). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker of testicular tissue. Therapeutic modulation of the expression or function of this gene may be useful in the treatment of male infertility and hypogonadism.

[0639] Panel 4.1D Summary: Ag4186 Expression of this gene is restricted to the kidney, thymus, and activated B lymphocytes (CTs=30-33). Thus, expression of this gene could be used to differentiate between the kidney derived sample and other samples on this panel and as a marker of kidney tissue. Therapeutic modulation of the expression or function of this gene could modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.

[0640] B. CG100760-01: LRR Protein

[0641] Expression of gene CG100760-01 was assessed using the primer-probe set Ag4192, described in Table BA. Results of the RTQ-PCR runs are shown in Tables BB, BC and BD.

TABLE BA
Probe Name Ag4192
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tattcttttgccgagcaaca-3′	20	882	150
Probe	TET-5′-caagttcatacacttgaacgtccagg-3′-TAMRA	26	918	151
Reverse	5′-aatgcaatggctgtacaaaact-3	22	944	152

[0642]

TABLE BB
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4192, Run		Ag4192, Run
Tissue Name	221157609	Tissue Name	221157609
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma*	0.2	Bladder	0.0
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	3.3	Gastric ca. KATO III	4.8
Melanoma*	0.0	Colon ca. SW-948	1.0
LOXIMVI
Melanoma* SK-	2.8	Colon ca. SW480	47.3
MEL-5
Squamous cell	0.0	Colon ca.* (SW480	5.7
carcinoma SCC-4		met) SW620
Testis Pool	4.7	Colon ca. HT29	1.0
Prostate ca.* (bone	7.8	Colon ca. HCT-116	5.3
met) PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	3.7
Placenta	0.0	Colon cancer tissue	0.1
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca.	0.3	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca. SK-OV-	0.0	Colon ca. SW-48	0.0
3
Ovarian ca.	1.4	Colon Pool	0.1
OVCAR-4
Ovarian ca.	0.2	Small Intestine Pool	0.8
OVCAR-5
Ovarian ca. IGROV-	0.0	Stomach Pool	0.4
1
Ovarian ca.	1.3	Bone Marrow Pool	0.0
OVCAR-8
Ovary	3.1	Fetal Heart	0.0
Breast ca. MCF-7	0.5	Heart Pool	0.3
Breast ca. MDA-	1.2	Lymph Node Pool	0.7
MB-231
Breast ca. BT 549	0.1	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	7.5	Spleen Pool	0.6
Breast Pool	0.0	Thymus Pool	0.8
Trachea	0.6	CNS cancer (glio/astro)	12.8
		U87-MG
Lung	0.2	CNS cancer (glio/astro)	15.2
		U-118-MG
Fetal Lung	0.0	CNS cancer	0.5
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	0.7	CNS cancer (astro) SF-	0.3
		539
Lung ca. LX-1	0.6	CNS cancer (astro)	0.9
		SNB-75
Lung ca. NCI-H146	7.7	CNS cancer (glio)	0.3
		SNB-19
Lung ca. SHP-77	100.0	CNS cancer (glio) SF-	14.4
		295
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	33.0	Brain (cerebellum)	0.3
Lung ca. NCI-H23	1.5	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus)	0.1
		Pool
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	4.8	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.8	Spinal Cord Pool	0.0
Kidney Pool	0.3	Adrenal Gland	0.0
Fetal Kidney	2.9	Pituitary gland Pool	0.1
Renal ca. 786-0	0.0	Salivary Gland	0.2
Renal ca. A498	0.6	Thyroid (female)	0.6
Renal ca. ACHN	0.0	Pancreatic ca.	0.3
		CAPAN2
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0643]

TABLE BC
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4192, Run		Ag4192, Run
Tissue Name	175226746	Tissue Name	175226746
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC	0.0
		none
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNFalpha + IL-1 beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNFalpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNFalpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	0.0
		none
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNFalpha + IL-1beta
CD45RA CD4	0.9	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	2.9	Coronery artery SMC	0.0
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	2.1	Astrocytes TNFalpha +	0.0
lymphocyte rest		IL-1beta
Secondary CD8	0.4	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	1.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.2
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN	0.9	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	0.9	NCI-H292 IL-9	0.9
LAK cells	0.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1	0.0
		beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha +	0.6
		IL-1 beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	2.1	Lung fibroblast IL-9	0.0
Ramos (B cell) none	58.6	Lung fibroblast IL-13	0.0
Ramos (B cell)	100.0	Lung fibroblast IFN	0.0
ionomycin		gamma
B lymphocytes PWM	2.6	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L	4.7	Dermal fibroblast	0.0
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	0.3	Dermal fibroblast	0.0
		CCD1070 IL-1 beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN	0.0
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	0.9
Macrophages rest	0.0	Lung	0.8
Macrophages LPS	0.0	Thymus	7.5
HUVEC none	0.0	Kidney	36.1
HUVEC starved	0.0

[0644]

TABLE BD
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4192, Run		Ag4192, Run
Tissue Name	268689533	Tissue Name	268689533
Colon cancer 1	0.0	Bladder cancer	0.0
		NAT 2
Colon cancer	0.8	Bladder cancer	0.0
NAT 1		NAT 3
Colon cancer 2	0.0	Bladder cancer	0.0
		NAT 4
Colon cancer	2.0	Adenocarcinoma of	4.7
NAT 2		the prostate 1
Colon cancer 3	3.3	Adenocarcinoma of	0.0
		the prostate 2
Colon cancer	2.4	Adenocarcinoma of	1.3
NAT 3		the prostate 3
Colon malignant	0.0	Adenocarcinoma of	0.0
cancer 4		the prostate 4
Colon normal	0.0	Prostate cancer	0.0
adjacent tissue		NAT 5
4
Lung cancer 1	0.0	Adenocarcinoma of	1.8
		the prostate 6
Lung NAT 1	0.0	Adenocarcinoma of	0.0
		the prostate 7
Lung cancer 2	6.7	Adenocarcinoma of	1.2
		the prostate 8
Lung NAT 2	0.0	Adenocarcinoma of	0.0
		the prostate 9
Squamous cell	4.3	Prostate cancer	0.0
carcinoma 3		NAT 10
Lung NAT 3	0.0	Kidney cancer 1	1.8
metastatic	5.0	Kidney NAT 1	3.2
melanoma 1
Melanoma 2	0.0	Kidney cancer 2	100.0
Melanoma 3	0.0	Kidney NAT 2	10.7
metastatic	2.4	Kidney cancer 3	0.9
melanoma 4
metastatic	20.0	Kidney NAT 3	2.1
melanoma 5
Bladder cancer	0.0	Kidney cancer 4	12.2
1
Bladder cancer	0.0	Kidney NAT 4	5.4
NAT 1
Bladder cancer	0.0
2

[0645] General_screening_panel_v1.4 Summary: Ag4192 Highest expression of the CG100760-01 is seen in a lung cancer cell line (CT=29.6). Moderate levels of expression are also seen in a cluster of cell lines derived from lung, colon, and brain cancers. Thus, expression of this gene could be used to differentiate the lung cancer cell line sample from other samples on this panel and as a marker of lung, colon and brain cancer. Furthermore, this restricted pattern of expression suggests that therapeutic modulation of the expression or function of this gene may be useful in the treatment of these cancers.

[0646] Panel 4.1D Summary: Ag4192 Expression of this gene is limited to a few samples on this panel, with highest expression of the CG100760-01 gene in Ramos B cells stimulated with ionomycin (CT=30.4). Lower but still significant levels of expression are seen in untreated Ramos B cells, activated B lymphocytes, kidney and thymus. B cells represent a principle component of immunity and contribute to the immune response in a number of important functional roles, including antibody production. Production of antibodies against self-antigens is a major component in autoimmune disorders. Since B cells play an important role in autoimmunity, inflammatory processes and inflammatory cascades, therapeutic modulation of this gene product may reduce or eliminate the symptoms of patients suffering from asthma, allergies, chronic obstructive pulmonary disease, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, osteoarthritis, systemic lupus erythematosus and other autoimmune disorders.

[0647] general oncology screening panel_v—2.4 Summary: Ag4192 Expression of the CG100760-01 gene is limited in kidney cancer (CT=32) and melanoma on this panel. This expression in cancer derived samples is consistent with expression seen in Panel 1.4. Thus, expression of this gene could be used to differentiate the kidney cancer sample from other samples on this panel and as a marker of kidney cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of kidney cancer.

[0648] C. CG101068-01: Claudin-9

[0649] Expression of gene CG101068-01 was assessed using the primer-probe set Ag4202, described in Table CA. Results of the RTQ-PCR runs are shown in Table CB.

TABLE CA
Probe Name Ag4202
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tataactccttgccatgcaaac-3′	22	1296	153
Probe	TET-5′-tcaagaggccaatatattcctggcca-3′-TAMRA	26	1320	154
Reverse	5′-gcatttgcatggctctaagtt-3′	21	1370	155

[0650]

TABLE CB
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4202, Run		Ag4202, Run
Tissue Name	221178754	Tissue Name	221178754
Adipose	0.4	Renal ca. TK-10	0.3
Melanoma*	0.0	Bladder	9.2
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	47.6
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	100.0
Melanoma*	0.0	Colon ca. SW-948	0.9
LOXIMVI
Melanoma* SK-	0.7	Colon ca. SW480	7.4
MEL-5
Squamous cell	0.0	Colon ca.* (SW480	0.0
carcinoma SCC-4		met) SW620
Testis Pool	0.0	Colon ca. HT29	0.0
Prostate ca.* (bone	0.0	Colon ca. HCT-116	2.1
met) PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	14.6
Placenta	3.6	Colon cancer tissue	7.5
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca.	0.7	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca. SK-OV-	6.7	Colon ca. SW-48	0.5
3
Ovarian ca.	0.0	Colon Pool	0.0
OVCAR-4
Ovarian ca.	12.9	Small Intestine Pool	0.0
OVCAR-5
Ovarian ca. IGROV-	2.3	Stomach Pool	0.0
1
Ovarian ca.	0.3	Bone Marrow Pool	0.0
OVCAR-8
Ovary	1.8	Fetal Heart	0.0
Breast ca. MCF-7	5.9	Heart Pool	0.0
Breast ca. MDA-	12.3	Lymph Node Pool	0.0
MB-231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	30.1	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	0.0	Thymus Pool	0.0
Trachea	3.1	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	4.2	CNS cancer	0.0
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-	0.5
		539
Lung ca. LX-1	1.9	CNS cancer (astro)	11.3
		SNB-75
Lung ca. NCI-H146	0.0	CNS cancer (glio)	2.6
		SNB-19
Lung ca. SHP-77	0.1	CNS cancer (glio) SF-	0.0
		295
Lung ca. A549	8.1	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	4.0	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus)	0.0
		Pool
Lung ca. HOP-62	0.5	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	1.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.0
Kidney Pool	0.0	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	0.1
Renal ca. A498	6.8	Thyroid (female)	3.5
Renal ca. ACHN	3.9	Pancreatic ca.	6.7
		CAPAN2
Renal ca. UO-31	0.0	Pancreas Pool	0.1

[0651] General_screening_panel_v1.4 Summary: Ag4202 Highest expression of the CG101068-01 gene is seen in a gastric cancer cell line (CT=26.5). Moderate levels of expression are seen in cell lines derived from pancreatic, brain, renal, lung, colon, breast and ovarian cancers. Thus, expression of this gene may be used to differentiate the gastric cancer cell line from other samples on this panel and as a marker of these cancers. This gene encodes a protein with homology to claudin, a family of proteins that are integral components of the tight junction. Members of this family have been shown to be upregulated in pancreatic cancer and colon cancer and in the former case proposed as novel targets for the treatment of this disease (Michl P. Gastroenterology September 2001;121(3):678-84; Miwa, N. Oncol Res 2001;12(11-12):469-76) Therefore, therapeutic modulation of the expression or function of this protein may be of use in the treatment of these cancers.

[0652] Claudin 11 has been shown to be a component of the CNS myelin and has been implicated in the regulation of growth and differentiation via signal transduction pathways.

[0653] Furthermore, evidence has been presented that shows that claudin 11 may be involved in the autoantigen that is responsible for the development of autoimmune demyelinating disease.(Bronstein J M. J Neurosci Res Mar. 15, 2000;59(6):706-11). Therefore, therapeutic modulation of the expression or function of this putative claudin may be of use in the treatment of demyelinating diseases such as multiple sclerosis and in restoring normal function to the CNS.

[0654] D. CG101231-01 and CG101231-02: Integral Membrane Protein

[0655] Expression of gene CG101231-01 and CG101231-02 was assessed using the primer-probe sets Ag4208 and Ag4997, described in Tables DA and DB. Results of the RTQ-PCR runs are shown in Tables DC and DD.

TABLE DA
Probe Name Ag4208
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cccactttgctcttacaaagac-3′	22	594	156
Probe	TET-5′-actttcattgaaggcagatcatacca-3′-TAMRA	26	622	157
Reverse	5′-ttttccattttcaccagattgt-3′	22	654	158

[0656]

TABLE DB
Probe Name Ag4997
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggagaaaattctttgggacaga-3′	22	1489	159
Probe	TET-5′-caacaaacaatgtttgcaatcagaatca-3′-TAMRA	28	1523	160
Reverse	5′-tgatgaatgtctcgaggctatt-3′	22	1554	161

[0657]

TABLE DC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4997, Run		Ag4997, Run
Tissue Name	222456716	Tissue Name	222456716
Adipose	1.2	Renal ca. TK-10	13.1
Melanoma*	26.4	Bladder	3.2
Hs688(A).T
Melanoma*	30.6	Gastric ca. (liver met.)	36.3
Hs688(B).T		NCI-N87
Melanoma* M14	8.2	Gastric ca. KATO III	29.3
Melanoma*	9.0	Colon ca. SW-948	4.0
LOXIMVI
Melanoma* SK-	4.5	Colon ca. SW480	33.4
MEL-5
Squamous cell	11.2	Colon ca.* (SW480	13.5
carcinoma SCC-4		met) SW620
Testis Pool	2.8	Colon ca. HT29	0.6
Prostate ca.* (bone	20.3	Colon ca. HCT-116	10.8
met) PC-3
Prostate Pool	12.4	Colon ca. CaCo-2	2.7
Placenta	0.3	Colon cancer tissue	5.8
Uterus Pool	1.4	Colon ca. SW1116	8.9
Ovarian ca.	10.4	Colon ca. Colo-205	5.9
OVCAR-3
Ovarian ca. SK-OV-	100.0	Colon ca. SW-48	1.4
3
Ovarian ca.	4.7	Colon Pool	5.6
OVCAR-4
Ovarian ca.	44.8	Small Intestine Pool	4.0
OVCAR-5
Ovarian ca. IGROV-	6.3	Stomach Pool	3.3
1
Ovarian ca.	10.4	Bone Marrow Pool	2.0
OVCAR-8
Ovary	3.0	Fetal Heart	17.2
Breast ca. MCF-7	11.0	Heart Pool	2.1
Breast ca. MDA-	22.4	Lymph Node Pool	6.9
MB-231
Breast ca. BT 549	67.8	Fetal Skeletal Muscle	2.0
Breast ca. T47D	66.4	Skeletal Muscle Pool	0.5
Breast ca. MDA-N	6.9	Spleen Pool	1.3
Breast Pool	5.5	Thymus Pool	5.3
Trachea	5.3	CNS cancer (glio/astro)	21.3
		U87-MG
Lung	1.4	CNS cancer (glio/astro)	17.7
		U-118-MG
Fetal Lung	29.1	CNS cancer	12.3
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	2.4	CNS cancer (astro) SF-	18.0
		539
Lung ca. LX-1	29.5	CNS cancer (astro)	49.7
		SNB-75
Lung ca. NCI-H146	12.0	CNS cancer (glio)	6.1
		SNB-19
Lung ca. SHP-77	17.8	CNS cancer (glio) SF-	20.6
		295
Lung ca. A549	11.9	Brain (Amygdala) Pool	9.3
Lung ca. NCI-H526	5.0	Brain (cerebellum)	6.9
Lung ca. NCI-H23	11.3	Brain (fetal)	19.6
Lung ca. NCI-H460	1.1	Brain (Hippocampus)	11.7
		Pool
Lung ca. HOP-62	8.5	Cerebral Cortex Pool	14.9
Lung ca. NCI-H522	19.6	Brain (Substantia nigra)	12.2
		Pool
Liver	0.0	Brain (Thalamus) Pool	17.2
Fetal Liver	21.5	Brain (whole)	10.4
Liver ca. HepG2	0.0	Spinal Cord Pool	18.9
Kidney Pool	4.8	Adrenal Gland	0.7
Fetal Kidney	12.9	Pituitary gland Pool	3.3
Renal ca. 786-0	11.6	Salivary Gland	1.0
Renal ca. A498	5.4	Thyroid (female)	4.0
Renal ca. ACHN	4.9	Pancreatic ca.	52.9
		CAPAN2
Renal ca. UO-31	7.8	Pancreas Pool	5.3

[0658]

TABLE DD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4997, Run		Ag4997, Run
Tissue Name	225428030	Tissue Name	225428030
Secondary Th1 act	2.7	HUVEC IL-1beta	3.2
Secondary Th2 act	3.8	HUVEC IFN gamma	4.0
Secondary Tr1 act	4.5	HUVEC TNF alpha + IFN	1.9
		gamma
Secondary Th1 rest	1.8	HUVEC TNF alpha + IL4	3.0
Secondary Th2 rest	2.0	HUVEC IL-11	11.9
Secondary Tr1 rest	1.4	Lung Microvascular EC	8.8
		none
Primary Th1 act	1.9	Lung Microvascular EC	3.9
		TNFalpha + IL-1 beta
Primary Th2 act	3.9	Microvascular Dermal EC	7.5
		none
Primary Tr1 act	3.5	Microsvasular Dermal EC	3.1
		TNFalpha + IL-1beta
Primary Th1 rest	1.7	Bronchial epithelium	38.7
		TNFalpha + IL1beta
Primary Th2 rest	3.9	Small airway epithelium	14.8
		none
Primary Tr1 rest	8.5	Small airway epithelium	24.0
		TNFalpha + IL-1beta
CD45RA CD4	7.9	Coronery artery SMC rest	13.3
lymphocyte act
CD45RO CD4	1.6	Coronery artery SMC	12.9
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	1.4	Astrocytes rest	10.4
Secondary CD8	1.7	Astrocytes TNFalpha +	12.0
lymphocyte rest		IL-1beta
Secondary CD8	0.4	KU-812 (Basophil) rest	78.5
lymphocyte act
CD4 lymphocyte none	0.2	KU-812 (Basophil)	100.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	2.0	CCD1106 (Keratinocytes)	31.2
CD95 CH11		none
LAK cells rest	1.6	CCD1106 (Keratinocytes)	17.0
		TNFalpha + IL-1beta
LAK cells IL-2	3.0	Liver cirrhosis	1.9
LAK cells IL-2 + IL-12	1.0	NCI-H292 none	9.5
LAK cells IL-2 + IFN	1.6	NCI-H292 IL-4	12.1
gamma
LAK cells IL-2 + IL-18	1.3	NCI-H292 IL-9	14.8
LAK cells	1.3	NCI-H292 IL-13	11.7
PMA/ionomycin
NK Cells IL-2 rest	3.2	NCI-H292 IFN gamma	8.5
Two Way MLR 3 day	0.5	HPAEC none	4.9
Two Way MLR 5 day	2.2	HPAEC TNF alpha + IL-1	3.8
		beta
Two Way MLR 7 day	0.4	Lung fibroblast none	13.4
PBMC rest	1.8	Lung fibroblast TNF alpha +	17.2
		IL-1 beta
PBMC PWM	0.5	Lung fibroblast IL-4	11.3
PBMC PHA-L	1.4	Lung fibroblast IL-9	22.7
Ramos (B cell) none	0.0	Lung fibroblast IL-13	8.9
Ramos (B cell)	0.0	Lung fibroblast IFN	8.7
ionomycin		gamma
B lymphocytes PWM	1.9	Dermal fibroblast	24.8
		CCD1070 rest
B lymphocytes CD40L	3.0	Dermal fibroblast	13.8
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	0.1	Dermal fibroblast	8.2
		CCD1070 IL-1 beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN	7.9
PMA/ionomycin		gamma
Dendritic cells none	3.1	Dermal fibroblast IL-4	15.7
Dendritic cells LPS	5.2	Dermal Fibroblasts rest	12.9
Dendritic cells anti-	3.7	Neutrophils TNFa + LPS	3.3
CD40
Monocytes rest	3.8	Neutrophils rest	20.2
Monocytes LPS	1.6	Colon	2.9
Macrophages rest	1.3	Lung	5.7
Macrophages LPS	0.1	Thymus	6.4
HUVEC none	3.6	Kidney	22.4
HUVEC starved	5.6

[0659] General_screening_panel_v1.4 Summary: Ag4997 Highest expression of the CG101231-01 gene is detected in an ovarian cancer SK-OV-3 cell line (CT=27). In addition, expression of this gene is also seen in cluster of cancer cell lines including pancreatic, CNS, colon, gastric, renal, lung, breast, ovarian, prostate, squamous cell carcinoma, and melanoma cancer cell lines. Overall, expression of this gene appears to be higher in samples derived from cancer cell lines than in normal tissues. Thus, expression of this gene could be used as a marker to detect the presence of cancer. Furthermore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of these cancers.

[0660] Among tissues with metabolic or endocrine function, this gene is expressed at low to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0661] Interestingly, this gene is expressed at much higher levels in fetal (CTs=29) when compared to adult lung and liver(CTs=33-38). This observation suggests that expression of this gene can be used to distinguish fetal from adult lung and liver. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance growth or development of liver and lung in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver and lung related diseases.

[0662] 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, this gene may play an important role in central nervous system and therapeutic modulation of this gene product may be useful in the treatment of neurological disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0663] Panel 4.1D Summary: Ag4997 Highest expression of the CG101231-01 gene is detected in PMA/ionomycin treated basophils (CT=29.4). This gene is expressed at low to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, lymphocytes, endothelial cell, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0664] E. CG101362-01: Prion Protein

[0665] Expression of gene CG101362-01 was assessed using the primer-probe set Ag6902, described in Table EA. Results of the RTQ-PCR runs are shown in Table EB.

TABLE EA
Probe Name Ag6902
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gaacactgggagcagatgtg-3′	20	173	162
Probe	TET-5′-aggaccatgctcgatcctctctggtaata-3′-TAMRA	29	224	163
Reverse	5′-aggaggatcacaggtggaga-3′	20	260	164

[0666]

TABLE EB
General_screening_panel_v1.6
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag6902, Run		Ag6902, Run
Tissue Name	278388399	Tissue Name	278388399
Adipose	3.0	Renal ca. TK-10	9.0
Melanoma*	23.5	Bladder	3.8
Hs688(A).T
Melanoma*	21.0	Gastric ca. (liver met.)	21.2
Hs688(B).T		NCI-N87
Melanoma* M14	50.3	Gastric ca. KATO III	15.9
Melanoma*	38.7	Colon ca. SW-948	2.6
LOXIMVI
Melanoma* SK-	14.3	Colon ca. SW480	24.5
MEL-5
Squamous cell	24.0	Colon ca.* (SW480	16.8
carcinoma SCC-4		met) SW620
Testis Pool	6.5	Colon ca. HT29	5.3
Prostate ca.* (bone	100.0	Colon ca. HCT-116	12.2
met) PC-3
Prostate Pool	6.4	Colon ca. CaCo-2	4.1
Placenta	1.5	Colon cancer tissue	6.6
Uterus Pool	4.1	Colon ca. SW1116	1.5
Ovarian ca.	2.5	Colon ca. Colo-205	2.3
OVCAR-3
Ovarian ca. SK-OV-	6.1	Colon ca. SW-48	0.7
3
Ovarian ca.	3.3	Colon Pool	9.6
OVCAR-4
Ovarian ca.	16.3	Small Intestine Pool	8.5
OVCAR-5
Ovarian ca. IGROV-	21.9	Stomach Pool	4.0
1
Ovarian ca.	16.8	Bone Marrow Pool	4.9
OVCAR-8
Ovary	6.0	Fetal Heart	8.2
Breast ca. MCF-7	2.2	Heart Pool	5.6
Breast ca. MDA-	32.1	Lymph Node Pool	11.3
MB-231
Breast ca. BT 549	41.2	Fetal Skeletal Muscle	4.0
Breast ca. T47D	1.7	Skeletal Muscle Pool	0.7
Breast ca. MDA-N	7.1	Spleen Pool	1.6
Breast Pool	12.1	Thymus Pool	3.7
Trachea	5.4	CNS cancer (glio/astro)	31.4
		U87-MG
Lung	2.1	CNS cancer (glio/astro)	30.4
		U-118-MG
Fetal Lung	13.4	CNS cancer	2.7
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	1.6	CNS cancer (astro) SF-	7.5
		539
Lung ca. LX-1	20.3	CNS cancer (astro)	32.8
		SNB-75
Lung ca. NCI-H146	1.0	CNS cancer (glio)	20.2
		SNB-19
Lung ca. SHP-77	1.7	CNS cancer (glio) SF-	66.4
		295
Lung ca. A549	17.6	Brain (Amygdala) Pool	18.6
Lung ca. NCI-H526	1.4	Brain (cerebellum)	67.8
Lung ca. NCI-H23	23.8	Brain (fetal)	10.9
Lung ca. NCI-H460	18.7	Brain (Hippocampus)	21.9
		Pool
Lung ca. HOP-62	28.5	Cerebral Cortex Pool	33.0
Lung ca. NCI-H522	4.0	Brain (Substantia nigra)	17.7
		Pool
Liver	0.5	Brain (Thalamus) Pool	30.4
Fetal Liver	5.5	Brain (whole)	29.3
Liver ca. HepG2	8.0	Spinal Cord Pool	13.2
Kidney Pool	14.0	Adrenal Gland	5.4
Fetal Kidney	2.4	Pituitary gland Pool	3.0
Renal ca. 786-0	8.0	Salivary Gland	2.2
Renal ca. A498	3.8	Thyroid (female)	3.5
Renal ca. ACHN	10.6	Pancreatic ca.	13.0
		CAPAN2
Renal ca. UO-31	26.1	Pancreas Pool	3.7

[0667] General_screening_panel_v1.6 Summary: Ag6902 Highest expression of the CG101362-01 gene is detected in prostate cancer cell line (CT=29.5). Moderate to low levels of expression of this gene is also seen in cluster of cancer cell lines derived from gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0668] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, fetal skeletal muscle, heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0669] Interestingly, this gene is expressed at much higher levels in fetal (CT=33.7) when compared to adult liver (CT=37). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver. In addition, the relative overexpression of this gene in fetal liver suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.

[0670] In addition, this gene is expressed at moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0671] F. CG101458-01: von Willebrand Domain Protein

[0672] Expression of gene CG101458-01 was assessed using the primer-probe set Ag4220, described in Table FA. Results of the RTQ-PCR runs are shown in Tables FB, FC, FD and FE.

TABLE FA
Probe Name Ag4220
			Start	SEQ ID
Primers	Sequences	Length	position	No
Forward	5′-ccaacaagcacacctttgac-3′	20	777	165
Probe	TET-5′-ctgtggagatcctcatccaccccag-3′-TAMRA	25	801	166
Reverse	5′-ctatcaggacatggggcata-3′	20	835	167

[0673]

TABLE FB
CNS_neurodegeneration_v1.0
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag4220, Run		Ag4220, Run
Tissue Name	215620528	Tissue Name	215620528
AD 1 Hippo	12.3	Control (Path) 3	0.0
		Temporal Ctx
AD 2 Hippo	32.8	Control (Path) 4	7.5
		Temporal Ctx
AD 3 Hippo	18.6	AD 1 Occipital Ctx	3.1
AD 4 Hippo	22.2	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	7.1	AD 3 Occipital Ctx	3.6
AD 6 Hippo	11.6	AD 4 Occipital Ctx	11.5
Control 2 Hippo	19.6	AD 5 Occipital Ctx	8.7
Control 4 Hippo	43.8	AD 5 Occipital Ctx	2.3
Control (Path) 3	98.6	Control 1 Occipital	1.8
Hippo		Ctx
AD 1 Temporal Ctx	4.9	Control 2 Occipital	5.5
		Ctx
AD 2 Temporal Ctx	12.8	Control 3 Occipital	0.7
		Ctx
AD 3 Temporal Ctx	2.8	Control 4 Occipital	12.2
		Ctx
AD 4 Temporal Ctx	12.9	Control (Path) 1	30.8
		Occipital Ctx
AD 5 Inf Temporal	7.2	Control (Path) 2	2.8
Ctx		Occipital Ctx
AD 5 Sup Temporal	100.0	Control (Path) 3	1.5
Ctx		Occipital Ctx
AD 6 Inf Temporal	8.1	Control (Path) 4	2.2
Ctx		Occipital Ctx
AD 6 Sup Temporal	15.1	Control 1 Parietal Ctx	2.6
Ctx
Control 1 Temporal	3.6	Control 2 Parietal Ctx	17.0
Ctx
Control 2 Temporal	2.7	Control 3 Parietal Ctx	1.4
Ctx
Control 3 Temporal	6.4	Control (Path) 1	14.2
Ctx		Parietal Ctx
Control 3 Temporal	5.8	Control (Path) 2	15.6
Ctx		Parietal Ctx
Control (Path) 1	11.0	Control (Path) 3	0.0
Temporal Ctx		Parietal Ctx
Control (Path) 2	5.0	Control (Path) 4	17.8
Temporal Ctx		Parietal Ctx

[0674]

TABLE FC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4220, Run		Ag4220, Run
Tissue Name	215620528	Tissue Name	215620528
Adipose	0.4	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	1.5
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma*	0.0	Colon ca. SW-948	0.0
LOXIMVI
Melanoma* SK-	0.0	Colon ca. SW480	0.0
MEL-5
Squamous cell	0.0	Colon ca.* (SW480	0.0
carcinoma SCC-4		met) SW620
Testis Pool	35.1	Colon ca. HT29	0.0
Prostate ca.* (bone	0.0	Colon ca. HCT-116	0.0
met) PC-3
Prostate Pool	0.1	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	13.1
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca.	0.0	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca. SK-OV-	0.0	Colon ca. SW-48	2.7
3
Ovarian ca.	0.5	Colon Pool	0.0
OVCAR-4
Ovarian ca.	0.6	Small Intestine Pool	1.9
OVCAR-5
Ovarian ca. IGROV-	1.2	Stomach Pool	0.1
1
Ovarian ca.	0.0	Bone Marrow Pool	0.4
OVCAR-8
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.2
Breast ca. MDA-	0.0	Lymph Node Pool	0.0
MB-231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.6
Breast ca. T47D	0.7	Skeletal Muscle Pool	0.9
Breast ca. MDA-N	0.0	Spleen Pool	0.5
Breast Pool	1.0	Thymus Pool	0.5
Trachea	0.4	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	3.7	CNS cancer	0.0
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	0.5	CNS cancer (astro) SF-	0.0
		539
Lung ca. LX-1	0.3	CNS cancer (astro)	0.0
		SNB-75
Lung ca. NCI-H146	0.0	CNS cancer (glio)	2.7
		SNB-19
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-	0.7
		295
Lung ca. A549	0.3	Brain (Amygdala) Pool	1.3
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.9
Lung ca. NCI-H23	0.0	Brain (fetal)	6.8
Lung ca. NCI-H460	0.0	Brain (Hippocampus)	8.0
		Pool
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	2.9
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	6.7
		Pool
Liver	0.0	Brain (Thalamus) Pool	8.8
Fetal Liver	0.0	Brain (whole)	5.2
Liver ca. HepG2	0.0	Spinal Cord Pool	8.9
Kidney Pool	0.0	Adrenal Gland	7.7
Fetal Kidney	21.9	Pituitary gland Pool	100.0
Renal ca. 786-0	0.0	Salivary Gland	17.6
Renal ca. A498	0.0	Thyroid (female)	8.6
Renal ca. ACHN	0.0	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	2.4	Pancreas Pool	5.1

[0675]

TABLE FD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4220, Run		Ag4220, Run
Tissue Name	174926565	Tissue Name	174926565
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC	0.0
		none
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNFalpha + IL-1 beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNFalpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNFalpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	0.0
		none
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNFalpha + IL-1beta
CD45RA CD4	1.5	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	2.4	Coronery artery SMC	0.0
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	2.5	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNFalpha +	0.0
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	1.5	NCI-H292 IL-9	0.0
LAK cells	0.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	2.5	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1	0.0
		beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha +	0.0
		IL-1 beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	2.8	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell)	0.0	Lung fibroblast IFN	0.0
ionomycin		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L	0.0	Dermal fibroblast	0.0
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast	0.0
		CCD1070 IL-1 beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN	0.0
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	5.4
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	2.8
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	0.0
Macrophages rest	0.0	Lung	2.9
Macrophages LPS	0.0	Thymus	11.0
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[0676]

TABLE FE
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4220, Run		Ag4220, Run
Tissue Name	268624960	Tissue Name	268624960
Colon cancer 1	0.8	Bladder cancer	0.0
		NAT 2
Colon cancer	0.0	Bladder cancer	0.0
NAT 1		NAT 3
Colon cancer 2	0.0	Bladder cancer	0.0
		NAT 4
Colon cancer	3.1	Adenocarcinoma of	0.6
NAT 2		the prostate 1
Colon cancer 3	1.8	Adenocarcinoma of	0.0
		the prostate 2
Colon cancer	5.3	Adenocarcinoma of	3.0
NAT 3		the prostate 3
Colon malignant	0.0	Adenocarcinoma of	3.6
cancer 4		the prostate 4
Colon normal	0.0	Prostate cancer	0.0
adjacent tissue		NAT 5
4
Lung cancer 1	0.0	Adenocarcinoma of	0.0
		the prostate 6
Lung NAT 1	0.7	Adenocarcinoma of	1.9
		the prostate 7
Lung cancer 2	16.5	Adenocarcinoma of	0.0
		the prostate 8
Lung NAT 2	0.7	Adenocarcinoma of	3.3
		the prostate 9
Squamous cell	0.0	Prostate cancer	0.7
carcinoma 3		NAT 10
Lung NAT 3	0.0	Kidney cancer 1	0.8
metastatic	27.4	Kidney NAT 1	89.5
melanoma 1
Melanoma 2	1.0	Kidney cancer 2	13.9
Melanoma 3	0.8	Kidney NAT 2	100.0
metastatic	0.9	Kidney cancer 3	3.0
melanoma 4
metastatic	0.0	Kidney NAT 3	92.7
melanoma 5
Bladder cancer	0.0	Kidney cancer 4	0.0
1
Bladder cancer	0.0	Kidney NAT 4	17.2
NAT 1
Bladder cancer	25.9
2

[0677] CNS_neurodegeneration_v1.0 Summary: Ag4220 This panel confirms the expression of the CG101458-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential use of this gene in treatment of central nervous system disorders.

[0678] General_screening_panel_v1.4 Summary: Ag4220 Highest expression of the CG101458-01 gene is detected in pituitary gland (CT=27.9). Furthermore, moderate to low levels of expression of this gene is also seen in other tissues with metabolic or endocrine functions including pancrease, adrenal gland, thyroid, skeletal muscle, and small intestine. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0679] In addition, this gene is expressed at moderate to low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0680] Moderate expression of this gene is also seen in testis. Therefore, therapeutic modulation of this gene product may be useful in the treatment of testis related diseases such as fertility and hypogonadism.

[0681] Significant expression of this gene is seen in fetal kidney and lung. Interestingly, this gene is expressed at much higher levels in fetal (CTs=30-32) when compared to adult kidney and lung(CTs=40). This observation suggests that expression of this gene can be used to distinguish fetal from adult kidney and lung. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance growth or development of kidney and lung 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 and lung related diseases.

[0682] Panel 4.1D Summary: Ag4220 Significant expression of the CG101458-01 gene is detected exclusively in kidney (CT=32.3). Therefore, expression of this gene may be used to distinguish kidney sample from other samples in this panel. In addition, therapeutic modulation of this gene product may be beneficial in the treatment of autoimmune and inflammatory diseases that affect kidney, including lupus and golomerulonephritis.

[0683] general oncology screening panel_v—2.4 Summary: Ag4220 Highest expression of the CG101458-01 gene is detected in control kidney samples (CTs=31). Interestingly, expression of this gene is higher in control samples as compared to kidney cancer samples. Therefore, expression of this gene may be used to distinguish between cancer and normal kidney samples. In addition, therapeutic modulation of this gene product that stimulates the function or expression of the this gene product may be beneficial in the treatment of kidney cancer.

[0684] In addition, significant expression of this gene is also seen in a bladder cancer, a lung cancer and a metastatic melanoma samples. Expression of this gene is higher in these cancer samples as compared to the adjacent control samples. Therefore, expression of this gene may be used as diagnostic marker for detection of these cancers and therapeutic modulation of this gene product may be beneficial in the treatment of these cancers.

[0685] G. CG101475-01: Novel Plasma Membrane Protein Containing Lectin C-type Domain

[0686] Expression of gene CG101475-01 was assessed using the primer-probe set Ag4214, described in Table GA. Results of the RTQ-PCR runs are shown in Tables GB, GC and GD.

TABLE GA
Probe Name Ag4214
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gggatgatgtgtttgcagatat-3′	22	195	168
Probe	TET-5′-cagagaaattgagtcaacttcagaaaacca-5′-TAMRA	30	238	169
Reverse	5′-agttatcctgctgctgttgga-3′	21	268	170

[0687]

TABLE GB
A1_comprehensive panel_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4214, Run		Ag4214, Run
Tissue Name	248080020	Tissue Name	248080020
110967 COPD-F	1.3	112427 Match Control	3.9
		Psoriasis-F
110980 COPD-F	0.0	112418 Psoriasis-M	2.7
110968 COPD-M	3.1	112723 Match Control	8.8
		Psoriasis-M
110977 COPD-M	0.3	112419 Psoriasis-M	1.5
110989 Emphysema-F	20.3	112424 Match Control	2.3
		Psoriasis-M
110992 Emphysema-F	1.5	112420 Psoriasis-M	3.9
110993 Emphysema-F	7.0	112425 Match Control	2.7
		Psoriasis-M
110994 Emphysema-F	3.3	104689 (MF) OA Bone-	11.0
		Backus
110995 Emphysema-F	3.1	104690 (MF) Adj “Normal”	6.7
		Bone-Backus
110996 Emphysema-F	0.0	104691 (MF) OA	1.3
		Synovium-Backus
110997 Asthma-M	2.6	104692 (BA) OA Cartilage-	0.0
		Backus
111001 Asthma-F	21.6	104694 (BA) OA Bone-	1.6
		Backus
111002 Asthma-F	11.5	104695 (BA) Adj “Normal”	3.8
		Bone-Backus
111003 Atopic Asthma-F	49.3	104696 (BA) OA	9.8
		Synovium-Backus
111004 Atopic Asthma-F	19.6	104700 (SS) OA Bone-	1.4
		Backus
111005 Atopic Asthma-F	24.5	104701 (SS) Adj “Normal”	1.6
		Bone-Backus
111006 Atopic Asthma-F	7.4	104702 (SS) OA	35.4
		Synovium-Backus
111417 Allergy-M	11.6	117093 OA Cartilage Rep7	2.6
112347 Allergy-M	0.0	112672 OA Bone5	1.4
112349 Normal Lung-F	0.0	112673 OA Synovium5	1.2
112357 Normal Lung-F	10.6	112674 OA Synovial Fluid	0.4
		cells5
112354 Normal Lung-M	0.8	117100 OA Cartilage	0.6
		Rep14
112374 Crohns-F	2.9	112756 OA Bone9	8.9
112389 Match Control	0.5	112757 OA Synovium9	0.0
Crohns-F
112375 Crohns-F	6.4	112758 OA Synovial Fluid	6.0
		Cells9
112732 Match Control	0.0	117125 RA Cartilage Rep2	16.4
Crohns-F
112725 Crohns-M	0.0	113492 Bone2 RA	0.4
112387 Match Control	0.4	113493 Synovium2 RA	0.4
Crohns-M
112378 Crohns-M	0.0	113494 Syn Fluid Cells RA	0.0
112390 Match Control	5.7	113499 Cartilage4 RA	0.8
Crohns-M
112726 Crohns-M	100.0	113500 Bone4 RA	1.2
112731 Match Control	28.9	113501 Synovium4 RA	0.6
Crohns-M
112380 Ulcer Col-F	30.8	113502 Syn Fluid Cells4	0.8
		RA
112734 Match Control	0.0	113495 Cartilage3 RA	0.8
Ulcer Col-F
112384 Ulcer Col-F	0.5	113496 Bone3 RA	0.2
112737 Match Control	28.9	113497 Synovium3 RA	0.0
Ulcer Col-F
112386 Ulcer Col-F	0.5	113498 Syn Fluid Cells3	0.2
		RA
112738 Match Control	0.0	117106 Normal Cartilage	1.3
Ulcer Col-F		Rep20
112381 Ulcer Col-M	1.7	113663 Bone3 Normal	0.0
112735 Match Control	1.2	113664 Synovium3 Normal	0.0
Ulcer Col-M
112382 Ulcer Col-M	0.0	113665 Syn Fluid Cells3	0.0
		Normal
112394 Match Control	0.0	117107 Normal Cartilage	1.8
Ulcer Col-M		Rep22
112383 Ulcer Col-M	12.0	113667 Bone4 Normal	0.0
112736 Match Control	0.0	113668 Synovium4 Normal	0.7
Ulcer Col-M
112423 Psoriasis-F	11.3	113669 Syn Fluid Cells4	0.9
		Normal

[0688]

TABLE GC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4214, Run		Ag4214, Run
Tissue Name	221254821	Tissue Name	221254821
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma*	0.9	Bladder	0.4
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma*	2.9	Colon ca. SW-948	0.0
LOXIMVI
Melanoma* SK-	0.8	Colon ca. SW480	0.0
MEL-5
Squamous cell	0.0	Colon ca.* (SW480	0.0
carcinoma SCC-4		met) SW620
Testis Pool	100.0	Colon ca. HT29	0.0
Prostate ca.* (bone	5.1	Colon ca. HCT-116	0.0
met) PC-3
Prostate Pool	0.3	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca.	0.0	Colon ca. Colo-205	0.0
OVCAR-3
Ovarian ca. SK-OV-	0.0	Colon ca. SW-48	0.0
3
Ovarian ca.	0.0	Colon Pool	0.0
OVCAR-4
Ovarian ca.	0.0	Small Intestine Pool	0.0
OVCAR-5
Ovarian ca. IGROV-	0.0	Stomach Pool	0.3
1
Ovarian ca.	0.0	Bone Marrow Pool	0.0
OVCAR-8
Ovary	0.3	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-	0.0	Lymph Node Pool	0.0
MB-231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.2
Breast ca. MDA-N	0.0	Spleen Pool	1.8
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer (glio/astro)	1.7
		U87-MG
Lung	0.0	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	0.3	CNS cancer	0.0
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-	0.4
		539
Lung ca. LX-1	0.0	CNS cancer (astro)	0.5
		SNB-75
Lung ca. NCI-H146	0.0	CNS cancer (glio)	0.0
		SNB-19
Lung ca. SHP-77	0.7	CNS cancer (glio) SF-	11.5
		295
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.3
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.4
Lung ca. NCI-H23	0.4	Brain (fetal)	0.3
Lung ca. NCI-H460	0.0	Brain (Hippocampus)	1.6
		Pool
Lung ca. HOP-62	0.4	Cerebral Cortex Pool	0.8
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.3
		Pool
Liver	0.2	Brain (Thalamus) Pool	1.6
Fetal Liver	0.3	Brain (whole)	0.3
Liver ca. HepG2	0.0	Spinal Cord Pool	0.9
Kidney Pool	0.7	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	0.0	Pancreas Pool	0.4

[0689]

TABLE GD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4214, Run		Ag4214, Run
Tissue Name	174261198	Tissue Name	174261198
Secondary Th1 act	0.0	HUVEC IL-1beta	22.5
Secondary Th2 act	0.0	HUVEC IFN gamma	13.8
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	3.7
Secondary Th2 rest	0.0	HUVEC IL-11	11.1
Secondary Tr1 rest	0.0	Lung Microvascular EC	0.0
		none
Primary Th1 act	0.0	Lung Microvascular EC	1.3
		TNFalpha + IL-1 beta
Primary Th2 act	0.0	Microvascular Dermal EC	9.5
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNFalpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNFalpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	0.0
		none
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNFalpha + IL-1beta
CD45RA CD4	0.9	Coronery artery SMC rest	10.3
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	15.4
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNFalpha +	0.0
lymphocyte rest		IL-1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	5.2
lymphocyte act
CD4 lymphocyte none	4.6	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	32.5	CCD1106 (Keratinocytes)	0.0
		TNFalpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells	5.7	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	6.0	HPAEC none	16.6
Two Way MLR 5 day	6.2	HPAEC TNF alpha + IL-1	3.2
		beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	18.0	Lung fibroblast TNF alpha +	0.0
		IL-1 beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell)	0.0	Lung fibroblast IFN	0.0
ionomycin		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L	0.0	Dermal fibroblast	0.0
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	6.7	Dermal fibroblast	0.0
		CCD1070 IL-1 beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN	3.3
PMA/ionomycin		gamma
Dendritic cells none	27.0	Dermal fibroblast IL-4	3.0
Dendritic cells LPS	2.3	Dermal Fibroblasts rest	0.0
Dendritic cells anti-	13.3	Neutrophils TNFa + LPS	8.5
CD40
Monocytes rest	54.3	Neutrophils rest	20.4
Monocytes LPS	100.0	Colon	0.0
Macrophages rest	5.8	Lung	3.1
Macrophages LPS	0.0	Thymus	0.0
HUVEC none	22.2	Kidney	0.0
HUVEC starved	12.8

[0690] AI_comprehensive panel_v1.0 Summary: Ag4214 Highest expression of the CG101475-01 gene is detected in Crohn's disease sample (CT=29). In addition, significant expression of this gene is also seen in samples derived from normal lung samples, COPD lung, emphysema, atopic asthma, asthma, allergy, Crohn's disease (normal matched control and diseased), ulcerative colitis(normal matched control and diseased), psoriasis (normal matched control and diseased), bone (Orthoarthritis and matched control), OA synovium and rheumatoid arthritis cartilage Rep2. Therefore, therapeutic modulation of this gene product may ameliorate symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis

[0691] General_screening_panel_v1.4 Summary: Ag4214 Moderate level of expression of the CG101475-01 gene is detected only intestis (CT=31). Therefore, expression of this gene may be used to distinguish testis from other samples used in this panel. In addition, therapeutic modulation of this gene may be useful in the treatment of testis related diseases, including fertility and hypogonadism.

[0692] Low levels of expression of this gene is also detected in one of the CNS cancer cell line. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of CNS cancer.

[0693] Panel 4.1D Summary: Ag4214 Highest expression of the CG101475-01 gene is detected in LPS treated monocytes (CT=33). Low levels of expression of this gene is also detected in resting monocytes and LAK cells. Therefore, expression of this gene may be used to distinguish monocytes and LAK cells from other samples used in this panel. The expression of this gene in resting cells suggests that the protein encoded by this gene may be involved in normal immunological processes associated with immune homeostasis. In addition, expression of this gene in activated monocytes suggests that this gene may be involved in their function as antigen-presenting cells and antibodies or small molecule therapeutics that block the function of this membrane protein may be useful as anti-inflammatory therapeutics for the treatment of autoimmune and inflammatory diseases.

[0694] H. CG101475-02: Novel Plasma Membrane Protein Containing Lectin C-type Domain

[0695] Expression of gene CG101475-02 was assessed using the primer-probe set Ag6376, described in Table HA. Please note that CG101475-02 represents a full-length physical clone

TABLE HA
Probe Name Ag6376
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gatggctctgttccctctc-3′	19	171	171
Probe	TET-5′-agtactaaagaacttgaccagatcaatgga-3′-TAMRA	30	130	172
Reverse	5′-cagcgagaaatataaatatttcct-3′	24	80	173

[0696] I. CG102575-01 and CG102575-02: Novel ATPase Associated with Various Cellular Activities

[0697] Expression of gene CG102575-01 and CG102575-02 was assessed using the primer-probe set Ag4238, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB, IC, ID and IE. Please note that CG102575-02 represents a full-length physical clone of the CG102575-01 gene, validating the prediction of the gene sequence.

TABLE IA
puz,19/30 Probe Name Ag4238
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-agatctggaggatacccagatc-3′	22	754	174
Probe	TET-5′-ccaacatcaagaagtactccttataaacca-3′-TAMRA	30	776	175
Reverse	5′-gcaaacatcactggctttatt-3′	22	824	176

[0698]

TABLE IB
CNS_neurodegeneration_v1.0
	Rel. Exp.(%)		Rel. Exp.(%)
	Ag4238, Run		Ag4238, Run
Tissue Name	224065201	Tissue Name	224065201
AD 1 Hippo	10.2	Control (Path) 3	8.2
		Temporal Ctx
AD 2 Hippo	22.8	Control (Path) 4	31.0
		Temporal Ctx
AD 3 Hippo	14.4	AD 1 Occipital	32.1
		Ctx
AD 4 Hippo	8.2	AD 2 Occipital	0.0
		Ctx
		(Missing)
AD 5 Hippo	100.0	AD 3 Occipital	12.9
		Ctx
AD 6 Hippo	68.3	AD 4 Occipital	20.9
		Ctx
Control 2	47.6	AD 5 Occipital	26.4
Hippo		Ctx
Control 4	17.4	AD 5 Occipital	59.5
Hippo		Ctx
Control (Path)	9.8	Control 1	6.2
3 Hippo		Occipital Ctx
AD 1 Temporal	27.7	Control 2	75.8
Ctx		Occipital Ctx
AD 2 Temporal	27.5	Control 3	37.4
Ctx		Occipital Ctx
AD 3 Temporal	10.3	Control 4	8.5
Ctx		Occipital Ctx
AD 4 Temporal	18.3	Control (Path) 1	85.3
Ctx		Occipital Ctx
AD 5 Inf	86.5	Control (Path) 2	12.1
Temporal Ctx		Occipital Ctx
AD 5 Sup	40.1	Control (Path) 3	11.4
Temporal Ctx		Occipital Ctx
AD 6 Inf	59.5	Control (Path) 4	19.6
Temporal Ctx		Occipital Ctx
AD 6 Sup	81.8	Control 1	8.0
Temporal Ctx		Parietal Ctx
Control 1	9.1	Control 2	53.2
Temporal Ctx		Parietal Ctx
Control 2	48.0	Control 3	17.7
Temporal Ctx		Parietal Ctx
Control 3	29.3	Control (Path) 1	81.8
Temporal Ctx		Parietal Ctx
Control 3	9.4	Control (Path) 2	30.1
Temporal Ctx		Parietal Ctx
Control (Path) 1	51.8	Control (Path) 3	8.5
Temporal Ctx		Parietal Ctx
Control (Path) 2	51.8	Control (Path) 4	52.5
Temporal Ctx		Parietal Ctx

[0699]

TABLE IC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4238, Run		Ag4238, Run
Tissue Name	222026508	Tissue Name	222026508
Adipose	12.2	Renal ca. TK-10	24.3
Melanoma*	24.5	Bladder	25.0
Hs688(A).T
Melanoma*	16.3	Gastric ca. (liver met.)	75.8
Hs688(B).T		NCI-N87
Melanoma* M14	35.8	Gastric ca. KATO III	60.7
Melanoma*	40.6	Colon ca. SW-948	18.9
LOXIMVI
Melanoma* SK-	32.1	Colon ca. SW480	26.8
MEL-5
Squamous cell	29.7	Colon ca.* (SW480	12.2
carcinoma SCC-4		met) SW620
Testis Pool	20.0	Colon ca. HT29	18.7
Prostate ca.* (bone	27.5	Colon ca. HCT-116	95.3
met) PC-3
Prostate Pool	10.7	Colon ca. CaCo-2	25.7
Placenta	2.6	Colon cancer tissue	13.5
Uterus Pool	8.4	Colon ca. SW1116	3.5
Ovarian ca.	29.1	Colon ca. Colo-205	3.6
OVCAR-3
Ovarian ca. SK-OV-	69.7	Colon ca. SW-48	3.0
3
Ovarian ca.	11.1	Colon Pool	37.9
OVCAR-4
Ovarian ca.	25.5	Small Intestine Pool	30.8
OVCAR-5
Ovarian ca. IGROV-	12.6	Stomach Pool	16.6
1
Ovarian ca.	7.8	Bone Marrow Pool	16.8
OVCAR-8
Ovary	7.9	Fetal Heart	24.3
Breast ca. MCF-7	13.4	Heart Pool	13.7
Breast ca. MDA-	55.1	Lymph Node Pool	38.7
MB-231
Breast ca. BT 549	100.0	Fetal Skeletal Muscle	11.1
Breast ca. T47D	40.1	Skeletal Muscle Pool	11.8
Breast ca. MDA-N	28.1	Spleen Pool	19.5
Breast Pool	38.2	Thymus Pool	25.7
Trachea	9.5	CNS cancer (glio/astro)	34.2
		U87-MG
Lung	6.1	CNS cancer (glio/astro)	47.0
		U-118-MG
Fetal Lung	20.0	CNS cancer	59.9
		(neuro; met) SK-N-AS
Lung ca. NCI-N417	5.4	CNS cancer (astro) SF-	11.2
		539
Lung ca. LX-1	24.0	CNS cancer (astro)	35.1
		SNB-75
Lung ca. NCI-H146	12.1	CNS cancer (glio)	13.2
		SNB-19
Lung ca. SHP-77	31.0	CNS cancer (glio) SF-	53.2
		295
Lung ca. A549	31.0	Brain (Amygdala) Pool	11.7
Lung ca. NCI-H526	7.3	Brain (cerebellum)	28.5
Lung ca. NCI-H23	54.7	Brain (fetal)	37.4
Lung ca. NCI-H460	42.6	Brain (Hippocampus)	11.0
		Pool
Lung ca. HOP-62	17.6	Cerebral Cortex Pool	16.7
Lung ca. NCI-H522	36.9	Brain (Substantia nigra)	8.8
		Pool
Liver	0.8	Brain (Thalamus) Pool	21.3
Fetal Liver	28.7	Brain (whole)	13.0
Liver ca. HepG2	11.3	Spinal Cord Pool	9.0
Kidney Pool	53.6	Adrenal Gland	14.2
Fetal Kidney	37.6	Pituitary gland Pool	5.3
Renal ca. 786-0	18.2	Salivary Gland	5.4
Renal ca. A498	12.7	Thyroid (female)	4.3
Renal ca. ACHN	12.2	Pancreatic ca.	0.0
		CAPAN2
Renal ca. UO-31	21.9	Pancreas Pool	28.1

[0700]

TABLE ID
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4238, Run		Ag4238, Run
Tissue Name	175226771	Tissue Name	175226771
Secondary Th1 act	64.2	HUVEC IL-1beta	21.8
Secondary Th2 act	52.1	HUVEC IFN gamma	19.5
Secondary Tr1 act	34.9	HUVEC TNF alpha + IFN	9.1
		gamma
Secondary Th1 rest	10.2	HUVEC TNF alpha + IL4	20.2
Secondary Th2 rest	7.8	HUVEC IL-11	22.5
Secondary Tr1 rest	8.5	Lung Microvascular EC	28.3
		none
Primary Th1 act	100.0	Lung Microvascular EC	9.5
		TNFalpha + IL-1 beta
Primary Th2 act	62.4	Microvascular Dermal EC	21.0
		none
Primary Tr1 act	62.4	Microsvasular Dermal EC	11.0
		TNFalpha + IL-1beta
Primary Th1 rest	12.5	Bronchial epithelium	10.4
		TNFalpha + IL1beta
Primary Th2 rest	11.2	Small airway epithelium	3.0
		none
Primary Tr1 rest	24.0	Small airway epithelium	6.2
		TNFalpha + IL-1beta
CD45RA CD4	25.2	Coronery artery SMC rest	7.3
lymphocyte act
CD45RO CD4	49.0	Coronery artery SMC	6.2
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	37.6	Astrocytes rest	3.3
Secondary CD8	39.5	Astrocytes TNFalpha +	3.8
lymphocyte rest		IL-1beta
Secondary CD8	19.3	KU-812 (Basophil) rest	62.9
lymphocyte act
CD4 lymphocyte none	12.4	KU-812 (Basophil)	79.6
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	14.3	CCD1106 (Keratinocytes)	23.3
CD95 CH11		none
LAK cells rest	19.8	CCD1106 (Keratinocytes)	14.1
		TNFalpha + IL-1beta
LAK cells IL-2	43.8	Liver cirrhosis	4.2
LAK cells IL-2 + IL-12	21.8	NCI-H292 none	9.3
LAK cells IL-2 + IFN	20.3	NCI-H292 IL-4	20.2
gamma
LAK cells IL-2 + IL-18	28.1	NCI-H292 IL-9	22.1
LAK cells	9.2	NCI-H292 IL-13	16.3
PMA/ionomycin
NK Cells IL-2 rest	53.2	NCI-H292 IFN gamma	15.1
Two Way MLR 3 day	24.7	HPAEC none	13.8
Two Way MLR 5 day	27.2	HPAEC TNF alpha + IL-1	14.2
		beta
Two Way MLR 7 day	24.3	Lung fibroblast none	10.4
PBMC rest	4.8	Lung fibroblast TNF alpha +	5.4
		IL-1 beta
PBMC PWM	27.7	Lung fibroblast IL-4	6.0
PBMC PHA-L	24.0	Lung fibroblast IL-9	13.0
Ramos (B cell) none	53.6	Lung fibroblast IL-13	11.8
Ramos (B cell)	45.7	Lung fibroblast IFN	11.3
ionomycin		gamma
B lymphocytes PWM	35.6	Dermal fibroblast	52.9
		CCD1070 rest
B lymphocytes CD40L	21.0	Dermal fibroblast	53.6
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	41.8	Dermal fibroblast	23.0
		CCD1070 IL-1 beta
EOL-1 dbcAMP	24.5	Dermal fibroblast IFN	13.1
PMA/ionomycin		gamma
Dendritic cells none	10.4	Dermal fibroblast IL-4	22.1
Dendritic cells LPS	4.6	Dermal Fibroblasts rest	6.3
Dendritic cells anti-	10.6	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	7.3	Neutrophils rest	2.6
Monocytes LPS	6.5	Colon	4.0
Macrophages rest	10.4	Lung	7.2
Macrophages LPS	2.0	Thymus	21.5
HUVEC none	18.9	Kidney	24.0
HUVEC starved	24.7

[0701]

TABLE IE
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4238, Run		Ag4238, Run
Tissue Name	268664314	Tissue Name	268664314
Colon cancer 1	16.0	Bladder cancer	0.0
		NAT 2
Colon cancer	4.0	Bladder cancer	0.0
NAT 1		NAT 3
Colon cancer 2	13.3	Bladder cancer	3.4
		NAT 4
Colon cancer	9.5	Adenocarcinoma of	16.3
NAT 2		the prostate 1
Colon cancer 3	14.8	Adenocarcinoma of	1.7
		the prostate 2
Colon cancer	14.5	Adenocarcinoma of	8.9
NAT 3		the prostate 3
Colon malignant	37.4	Adenocarcinoma of	25.7
cancer 4		the prostate 4
Colon normal	1.9	Prostate cancer	1.6
adjacent tissue		NAT 5
4
Lung cancer 1	9.2	Adenocarcinoma of	1.1
		the prostate 6
Lung NAT 1	0.0	Adenocarcinoma of	3.0
		the prostate 7
Lung cancer 2	100.0	Adenocarcinoma of	0.8
		the prostate 8
Lung NAT 2	1.6	Adenocarcinoma of	10.6
		the prostate 9
Squamous cell	26.4	Prostate cancer	0.0
carcinoma 3		NAT 10
Lung NAT 3	0.0	Kidney cancer 1	18.2
metastatic	15.2	Kidney NAT 1	13.5
melanoma 1
Melanoma 2	1.5	Kidney cancer 2	30.1
Melanoma 3	1.9	Kidney NAT 2	12.6
metastatic	24.0	Kidney cancer 3	27.0
melanoma 4
metastatic	38.4	Kidney NAT 3	7.6
melanoma 5
Bladder cancer	0.0	Kidney cancer 4	7.3
1
Bladder cancer	0.0	Kidney NAT 4	3.0
NAT 1
Bladder cancer	1.9
2

[0702] CNS_neurodegeneration_v1.0 Summary: Ag4238 This panel does not show differential expression of this gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.

[0703] General_screening_panel_v1.4 Summary: Ag4238 Highest expression of this gene is seen in a breast cancer cell line (CT=30.2). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancers. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0704] 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 among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0705] Interestingly, this gene is expressed at much higher levels in fetal (CT=32) when compared to adult liver (CT=37). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver. In addition, the relative overexpression of this gene in fetal liver suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.

[0706] This gene is also expressed at low but significant levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0707] Panel 4.1D Summary: Ag4238 Highest expression of this gene is seen in acutely activated Th1 cells (CT=33.2). In addition, this gene is expressed in a wide range of cell types including activated T cells, LAK cells, dermal fibroblasts, and basophils. This pattern of expression is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0708] general oncology screening panel_v—2.4 Summary: Ag4238 This gene is widely expressed in this panel, with highest expression in lung cancer (CT=32.6). In addition, this gene is more highly expressed in lung and kidney cancer than in the corresponding normal adjacent tissue. In addition, significant expression of this gene is also associated with colon, and prostate cancer and also with melanoma. Thus, expression of this gene could be used as a marker of these cancers. Furthemore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of lung and kidney cancer.

[0709] J. CG102615-01: mat8

[0710] Expression of gene CG102615-01 was assessed using the primer-probe set Ag2173, described in Table JA. Results of the RTQ-PCR runs are shown in Tables JB, JC, JD and JE.

TABLE JA
uz,17/29 Probe Name Ag2173
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-acttgaactccaggatggaatt-3′	22	332	177
Probe	TET-5′-cttcctcctctgctgggactcctttg-3′-TAMRA	26	354	178
Reverse	5′-cttgcgagaggtgagatgag-3′	20	391	179

[0711]

TABLE JB
Panel 1.3D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag2173, Run		Ag2173, Run
Tissue Name	165750872	Tissue Name	165750872
Liver adenocarcinoma	8.6	Kidney (fetal)	0.6
Pancreas	0.3	Renal ca. 786-0	0.0
Pancreatic ca. CAPAN 2	1.8	Renal ca. A498	0.1
Adrenal gland	0.1	Renal ca. RXF 393	0.0
Thyroid	0.1	Renal ca. ACHN	0.0
Salivary gland	3.6	Renal ca. UO-31	0.2
Pituitary gland	0.3	Renal ca. TK-10	0.0
Brain (fetal)	0.0	Liver	0.0
Brain (whole)	0.0	Liver (fetal)	0.0
Brain (amygdala)	0.1	Liver ca. (hepatoblast)	0.6
		HepG2
Brain (cerebellum)	0.0	Lung	4.7
Brain (hippocampus)	0.2	Lung (fetal)	3.8
Brain (substantia nigra)	0.1	Lung ca. (small cell)	1.3
		LX-1
Brain (thalamus)	0.1	Lung ca. (small cell)	1.5
		NCI-H69
Cerebral Cortex	0.5	Lung ca. (s. cell var.)	0.0
		SHP-77
Spinal cord	0.8	Lung ca. (large	0.0
		cell) NCI-H460
glio/astro U87-MG	0.0	Lung ca. (non-sm. cell)	0.0
		A549
glio/astro U-118-MG	0.1	Lung ca. (non-s. cell)	0.0
		NCI-H23
astrocytoma SW1783	0.0	Lung ca. (non-s. cell)	0.0
		HOP-62
neuro*; met SK-N-AS	0.0	Lung ca. (non-s. cl)	0.0
		NCI-H522
astrocytoma SF-539	0.1	Lung ca. (squam.) SW	0.3
		900
astrocytoma SNB-75	0.2	Lung ca. (squam.) NCI-	5.2
		H596
glioma SNB-19	0.0	Mammary gland	3.7
glioma U251	0.0	Breast ca.* (pl. ef)	7.9
		MCF-7
glioma SF-295	0.0	Breast ca.* (pl. ef)	0.0
		MDA-MB-231
Heart (fetal)	0.0	Breast ca.* (pl. ef)	1.0
		T47D
Heart	0.1	Breast ca. BT-549	0.0
Skeletal muscle (fetal)	0.6	Breast ca. MDA-N	0.0
Skeletal muscle	0.1	Ovary	1.0
Bone marrow	0.1	Ovarian ca. OVCAR-3	0.2
Thymus	1.6	Ovarian ca. OVCAR-4	0.1
Spleen	0.1	Ovarian ca. OVCAR-5	1.7
Lymph node	0.0	Ovarian ca. OVCAR-8	0.0
Colorectal	100.0	Ovarian ca. IGROV-1	0.0
Stomach	5.2	Ovarian ca.* (ascites)	0.0
		SK-OV-3
Small intestine	0.5	Uterus	0.1
Colon ca. SW480	0.0	Placenta	3.1
Colon ca.*	0.1	Prostate	12.7
SW620 (SW480 met)
Colon ca. HT29	2.9	Prostate ca.* (bone	0.0
		met) PC-3
Colon ca. HCT-116	0.2	Testis	0.0
Colon ca. CaCo-2	3.3	Melanoma Hs688(A).T	0.0
Colon ca.	6.1	Melanoma* (met)	0.0
tissue (ODO3866)		Hs688(B).T
Colon ca. HCC-2998	1.3	Melanoma UACC-62	5.1
Gastric ca.* (liver met)	15.4	Melanoma M14	5.4
NCI-N87
Bladder	6.1	Melanoma LOX IMVI	0.0
Trachea	21.6	Melanoma* (met) SK-	0.0
		MEL-5
Kidney	0.5	Adipose	0.5

[0712]

TABLE JC
Panel 2D
	Rel. Exp. (%) Ag2173,		Rel. Exp. (%) Ag2173,
Tissue Name	Run 162309316	Tissue Name	Run 162309316
Normal Colon	94.6	Kidney Margin 8120608	0.3
CC Well to Mod Diff	9.3	Kidney Cancer 8120613	0.0
(ODO3866)
CC Margin (ODO3866)	33.2	Kidney Margin 8120614	0.6
CC Gr.2 rectosigmoid	15.7	Kidney Cancer 9010320	0.8
(ODO3868)
CC Margin (ODO3868)	2.3	Kidney Margin 9010321	0.3
CC Mod Diff (ODO3920)	13.7	Normal Uterus	0.0
CC Margin (ODO3920)	40.1	Uterus Cancer 064011	4.6
CC Gr.2 ascend colon	52.9	Normal Thyroid	0.1
(ODO3921)
CC Margin (ODO3921)	36.6	Thyroid Cancer 064010	0.2
CC from Partial Hepatectomy	13.1	Thyroid Cancer A302152	0.4
(ODO4309) Mets
Liver Margin (ODO4309)	0.1	Thyroid Margin A302153	0.0
Colon mets to lung	11.3	Normal Breast	9.9
(OD04451-01)
Lung Margin (OD04451-02)	8.7	Breast Cancer (OD04566)	10.7
Normal Prostate 6546-1	100.0	Breast Cancer (OD04590-	37.9
		01)
Prostate Cancer (OD04410)	31.2	Breast Cancer Mets	58.2
		(OD04590-03)
Prostate Margin (OD04410)	32.3	Breast Cancer Metastasis	14.8
		(OD04655-05)
Prostate Cancer (OD04720-	11.1	Breast Cancer 064006	11.0
01)
Prostate Margin (OD04720-	22.2	Breast Cancer 1024	20.4
02)
Normal Lung 061010	16.8	Breast Cancer 9100266	26.6
Lung Met to Muscle	0.1	Breast Margin 9100265	10.6
(ODO4286)
Muscle Margin (ODO4286)	0.1	Breast Cancer A209073	27.0
Lung Malignant Cancer	33.0	Breast Margin A209073	9.3
(OD03126)
Lung Margin (OD03126)	13.5	Normal Liver	0.0
Lung Cancer (OD04404)	64.6	Liver Cancer 064003	0.0
Lung Margin (OD04404)	9.9	Liver Cancer 1025	0.0
Lung Cancer (OD04565)	34.4	Liver Cancer 1026	0.5
Lung Margin (OD04565)	5.5	Liver Cancer 6004-T	0.0
Lung Cancer (OD04237-01)	4.0	Liver Tissue 6004-N	0.1
Lung Margin (OD04237-02)	10.7	Liver Cancer 6005-T	0.4
Ocular Mel Met to Liver	0.0	Liver Tissue 6005-N	0.0
(ODO4310)
Liver Margin (ODO4310)	0.0	Normal Bladder	11.0
Melanoma Mets to Lung	5.1	Bladder Cancer 1023	15.5
(OD04321)
Lung Margin (OD04321)	9.5	Bladder Cancer A302173	20.4
Normal Kidney	0.6	Bladder Cancer	84.7
		(OD04718-01)
Kidney Ca, Nuclear grade 2	0.5	Bladder Normal Adjacent	0.3
(OD04338)		(OD04718-03)
Kidney Margin (OD04338)	1.4	Normal Ovary	0.5
Kidney Ca Nuclear grade 1/2	0.0	Ovarian Cancer 064008	5.5
(OD04339)
Kidney Margin (OD04339)	0.5	Ovarian Cancer	3.0
		(OD04768-07)
Kidney Ca, Clear cell type	0.0	Ovary Margin	0.0
(OD04340)		(OD04768-08)
Kidney Margin (OD04340)	0.7	Normal Stomach	18.3
Kidney Ca, Nuclear grade 3	0.1	Gastric Cancer 9060358	3.3
(OD04348)
Kidney Margin (OD04348)	0.4	Stomach Margin 9060359	22.5
Kidney Cancer (OD04622-01)	0.1	Gastric Cancer 9060395	24.8
Kidney Margin (OD04622-	1.1	Stomach Margin 9060394	20.6
03)
Kidney Cancer (OD04450-01)	0.0	Gastric Cancer 9060397	27.2
Kidney Margin (OD04450-	0.9	Stomach Margin 9060396	30.4
03)
Kidney Cancer 8120607	0.0	Gastric Cancer 064005	20.6

[0713]

TABLE JD
Panel 4D
	Rel. Exp. (%) Ag2173,		Rel. Exp. (%) Ag2173,
Tissue Name	Run 162292974	Tissue Name	Run 162292974
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.1	Bronchial epithelium	61.6
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	23.2
Primary Tr1 rest	0.0	Small airway epithelium	76.8
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha + IL-	0.0
lymphocyte rest		1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.3
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.3
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	21.2
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	20.4
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.2
LAK cells IL-2 + IL-12	0.0	Lupus kidney	0.3
LAK cells IL-2 + IFN	0.0	NCI-H292 none	100.0
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-4	60.3
LAK cells	0.0	NCI-H292 IL-9	80.7
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IL-13	42.9
Two Way MLR 3 day	0.0	NCI-H292 IFN gamma	62.9
Two Way MLR 5 day	0.0	HPAEC none	0.0
Two Way MLR 7 day	0.0	HPAEC TNF alpha + IL-1beta	0.0
PBMC rest	0.0	Lung fibroblast none	0.0
PBMC PWM	0.0	Lung fibroblast TNF alpha +	0.0
		IL-1beta
PBMC PHA-L	0.0	Lung fibroblast IL-4	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IL-13	0.0
B lymphocytes PWM	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070	0.0
and IL-4		rest
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	0.0
		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	0.0
PMA/ionomycin		IL-1beta
Dendritic cells none	0.0	Dermal fibroblast IFN gamma	0.1
Dendritic cells LPS	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells anti-CD40	0.1	IBD Colitis 2	0.1
Monycytes rest	0.0	IBD Crohn's	0.1
Monocytes LPS	0.0	Colon	7.4
Macrophages rest	0.0	Lung	3.5
Macrophages LPS	0.0	Thymus	0.5
HUVEC none	0.0	Kidney	0.6
HUVEC starved	0.0

[0714]

TABLE JE
Panel 5 Islet
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag2173, Run		Ag2173, Run
Tissue Name	279370794	Tissue Name	279370794
97457_Patient-	1.9	94709_Donor 2 AM - A_adipose	0.0
02go_adipose
97476_Patient-	0.0	94710_Donor 2 AM - B_adipose	0.3
07sk_skeletal muscle
97477_Patient-07ut_uterus	0.0	94711_Donor 2 AM - C_adipose	0.0
97478_Patient-	60.7	94712_Donor 2 AD - A_adipose	0.0
07pl_placenta
99167_Bayer Patient 1	47.6	94713_Donor 2 AD - B_adipose	2.1
97482_Patient-08ut_uterus	1.2	94714_Donor 2 AD - C_adipose	0.3
97483_Patient-	69.3	94742_Donor 3 U - A_Mesenchymal	0.0
08pl_placenta		Stem Cells
97486_Patient-	0.0	94743_Donor 3 U - B_Mesenchymal	0.0
09sk_skeletal muscle		Stem Cells
97487_Patient-09ut_uterus	0.2	94730_Donor 3 AM - A_adipose	1.1
97488_Patient-	31.6	94731_Donor 3 AM - B_adipose	0.7
09pl_placenta
97492_Patient-10ut_uterus	2.7	94732_Donor 3 AM - C_adipose	1.0
97493_Patient-	73.7	94733_Donor 3 AD —A_adipose	0.8
10pl_placenta
97495_Patient-	0.6	94734_Donor 3 AD —B_adipose	0.2
11go_adipose
97496_Patient-	1.1	94735_Donor 3 AD —C_adipose	1.0
11sk_skeletal muscle
97497_Patient-11ut_uterus	1.0	77138_Liver_HepG2untreated	100.0
97498_Patient-	31.4	73556_Heart_Cardiac stromal cells	0.0
11pl_placenta		(primary)
97500_Patient-	0.0	81735_Small Intestine	61.6
12go_adipose
97501_Patient-	0.4	72409_Kidney_Proximal Convoluted	0.0
12sk_skeletal muscle		Tubule
97502_Patient-12ut_uterus	1.3	82685_Small intestine_Duodenum	12.2
97503_Patient-	68.8	90650_Adrenal_Adrenocortical	0.0
12pl_placenta		adenoma
94721_Donor 2 U —	0.5	72410_Kidney_HRCE	1.9
A_Mesenchymal Stem
Cells
94722_Donor 2 U —	0.8	72411_Kidney_HRE	0.6
B_Mesenchymal Stem
Cells
94723_Donor 2 U —	0.3	73139_Uterus_Uterine smooth	0.0
C_Mesenchymal Stem		muscle cells
Cells

[0715] Panel 1.3D Summary: Ag2173 Highest expression of the CG102615-01 gene is detected in colorectal sample (CT=24). Therefore, expression of this gene may be used to distinguish this sample from other samples used in this panel. In addition, significant expression of this gene is seen in number of cancer cell lines including melanoma, ovarian, breast, lung, colon, pancreatic and liver cancer cell lines. The CG102615-01 gene codes for chloride conductane inducer protein MAT-8 precursor. MAT-8 is known to mediate chloride flow, affecting the membrane potential of the cell (Morrison et al., 1995, J. Biol. Chem. 270:2176-2182, PMID=7836447). Changes in membrane potential can affect tumor cell and associated smooth muscle cells (therefore tumor-induced vasculature) growth and motility. In this respect the expression of this gene in fetal muscle is an indication of a role in muscle growth/development. Therapeutic targeting of the CG102615-01 gene product with a monoclonal antibody is anticipated to limit or block the extent of tumor cell growth and motility and tumor associated angiogenesis, preferably in breast, ovarian bladder, lung tumors.

[0716] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, thyroid, pituitary gland, skeletal muscle, heart, and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0717] In addition, this gene is expressed at low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0718] Panel 2D Summary: Ag2173 Highest expression of the CG102615-01 gene is detected in normal prostate (CT=22.8). High expression of this gene is seen in normal and cancer samples derived from colon, prostate, lung, melanoma, uterus, thyroid, breast, liver, bladder, ovary, and stomach. Interestingly, expression of this gene is higher in ovarian, bladder, breast, uterine, and lung cancer samples as compared to their corresponding adjacent control samples. Therefore, therapeutic targeting of the CG102615-01 gene product with antibodies or small molecule inhibitors is anticipated to limit or block the extent of tumor cell growth and motility as well as tumor associated angiogenesis, preferably in ovarian, bladder, breast, uterine, and lung cancer.

[0719] Also the expression of this gene is decreased in kidney cancers compared to the normal adjacent tissues. Hence the protein product or fragments of this protein may be useful in the treatment of kidney cancer.

[0720] Panel 4D Summary: Ag2173 Highest expression of the CG102615-01 gene is detected in NCI-H292 cells (CT=23.8). High to moderate level of this gene is also found in lung derived cell types: small airway and bronchial epithelium treated with TNF-a and Il-1, lung fibroblast treated with IFN. This pattern of expression suggests a role for this gene in pathology of lung inflammatory dideases. Therefore therapeutic modulation of this gene product may be beneficial in the treatment of asthma, emphysema or lung infection.

[0721] Interestingly, high to low levels of expression of this gene is also seen in keratinocytes, basophils, IFN gamma treated dermal fibroblasts, liver cirrhosis, IBD colitis and Crohn's disease samples and normal tissues represented by colon, lung, thymus and kidney. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of autoimmune and inflammatory disease associated with these cell types and tissues including asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0722] Panel 5 Islet Summary: Ag2173 Highest expression of the CG102615-01 gene is detected in untreated liver HepG2 samples (CT=28.6). In addition, high to low levels of expression of this gene is also seen in islet cells, placenta, uterus, small intestine, kidney and adipose tissues. The CG102615-01 gene codes for chloride conductane inducer protein MAT-8 precursor. MAT-8 is known to mediate chloride flow, affecting the membrane potential of the cell (Morrison et al., 1995, J. Biol. Chem. 270:2176-2182, PMID=7836447). Since membrane potential is critical in the secretory process in the beta cell, therapeutic modulation of the activity of this gene may prove useful in enhancing insulin secretion in Type II diabetes.

[0723] K. CG102646-01: High Affinity Proline Permease Like

[0724] Expression of gene CG102646-01 was assessed using the primer-probe set Ag4241, described in Table KA.

TABLE KA
Probe Name Ag4241
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggcagcaattatgagtacgatt-3′	22	1035	180
Probe	TET-5′-tcccaattacttgtgacttcaagttca-3′	27	1000	181
Reverse	5′-tgcttcttcaccacgaattaa-3′	21	1108	182

[0725] L. CG102878-01 and CG102878-02: Hypothetical Transmembrane

[0726] Expression of gene CG102878-01 and CG102878-02 was assessed using the primer-probe set Ag4246, described in Table LA. Results of the RTQ-PCR runs are shown in Tables LB, LC, LD and LE. Please note that CG102878-02 represents a full-length physical clone of the CG102878-01 gene, validating the prediction of the gene sequence.

TABLE LA
Probe Name Ag4246
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cctccctggtagaggtcaac-3′	20	824	183
Probe	TET-5′-ctactcagtgcccagcagccaggag-3′-TAMRA	25	849	184
Reverse	5′-tgtctgcatgcagcctatg-3′	19	885	185

[0727]

TABLE LB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%) Ag4246, Run		Rel. Exp. (%) Ag4246, Run
Tissue Name	224077627	Tissue Name	224077627
AD 1 Hippo	31.0	Control (Path) 3	40.3
		Temporal Ctx
AD 2 Hippo	56.3	Control (Path) 4	46.3
		Temporal Ctx
AD 3 Hippo	22.4	AD 1 Occipital Ctx	20.6
AD 4 Hippo	28.5	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	79.0	AD 3 Occipital Ctx	21.3
AD 6 Hippo	76.3	AD 4 Occipital Ctx	31.6
Control 2 Hippo	65.5	AD 5 Occipital Ctx	83.5
Control 4 Hippo	49.0	AD 6 Occipital Ctx	41.5
Control (Path) 3 Hippo	35.4	Control 1 Occipital Ctx	20.2
AD 1 Temporal Ctx	30.1	Control 2 Occipital Ctx	92.0
AD 2 Temporal Ctx	36.3	Control 3 Occipital Ctx	70.7
AD 3 Temporal Ctx	14.3	Control 4 Occipital Ctx	28.7
AD 4 Temporal Ctx	28.1	Control (Path) 1	100.0
		Occipital Ctx
AD 5 Inf Temporal Ctx	80.7	Control (Path) 2	49.0
		Occipital Ctx
AD 5 Sup Temporal	66.4	Control (Path) 3	36.1
Ctx		Occipital Ctx
AD 6 Inf Temporal Ctx	64.2	Control (Path) 4	60.3
		Occipital Ctx
AD 6 Sup Temporal	78.5	Control 1 Parietal Ctx	24.8
Ctx
Control 1 Temporal	35.4	Control 2 Parietal Ctx	83.5
Ctx
Control 2 Temporal	68.3	Control 3 Parietal Ctx	34.4
Ctx
Control 3 Temporal	41.2	Control (Path) 1	71.2
Ctx		Parietal Ctx
Control 3 Temporal	32.3	Control (Path) 2	52.5
Ctx		Parietal Ctx
Control (Path) 1	55.5	Control (Path) 3	32.5
Temporal Ctx		Parietal Ctx
Control (Path) 2	67.8	Control (Path) 4	76.8
Temporal Ctx		Parietal Ctx

[0728]

TABLE LC
General_screening_panel_v1.4
	Rel. Exp. (%) Ag4246,		Rel. Exp. (%) Ag4246,
Tissue Name	Run 222018714	Tissue Name	Run 222018714
Adipose	1.1	Renal ca. TK-10	3.5
Melanoma*	4.8	Bladder	5.7
Hs688(A).T
Melanoma*	2.8	Gastric ca. (liver met.)	12.8
Hs688(B).T		NCI-N87
Melanoma* M14	3.1	Gastric ca. KATO III	12.7
Melanoma* LOXIMVI	3.3	Colon ca. SW-948	6.2
Melanoma* SK-MEL-5	3.2	Colon ca. SW480	12.0
Squamous cell	1.6	Colon ca.* (SW480 met)	7.5
carcinoma SCC-4		SW620
Testis Pool	2.5	Colon ca. HT29	7.1
Prostate ca.* (bone met)	1.6	Colon ca. HCT-116	8.4
PC-3
Prostate Pool	2.7	Colon ca. CaCo-2	10.6
Placenta	2.6	Colon cancer tissue	4.8
Uterus Pool	0.8	Colon ca. SW1116	9.7
Ovarian ca. OVCAR-3	18.7	Colon ca. Colo-205	4.0
Ovarian ca. SK-OV-3	14.1	Colon ca. SW-48	5.0
Ovarian ca. OVCAR-4	3.3	Colon Pool	4.9
Ovarian ca. OVCAR-5	27.5	Small Intestine Pool	3.4
Ovarian ca. IGROV-1	14.9	Stomach Pool	1.9
Ovarian ca. OVCAR-8	14.2	Bone Marrow Pool	1.1
Ovary	3.3	Fetal Heart	3.8
Breast ca. MCF-7	5.3	Heart Pool	2.4
Breast ca. MDA-MB-	9.4	Lymph Node Pool	3.2
231
Breast ca. BT 549	13.5	Fetal Skeletal Muscle	0.6
Breast ca. T47D	100.0	Skeletal Muscle Pool	3.5
Breast ca. MDA-N	9.7	Spleen Pool	4.5
Breast Pool	4.2	Thymus Pool	2.6
Trachea	2.6	CNS cancer (glio/astro)	12.5
		U87-MG
Lung	0.4	CNS cancer (glio/astro) U-	9.1
		118-MG
Fetal Lung	3.7	CNS cancer (neuro; met)	11.3
		SK-N-AS
Lung ca. NCI-N417	1.9	CNS cancer (astro) SF-539	5.1
Lung ca. LX-1	6.9	CNS cancer (astro) SNB-	13.5
		75
Lung ca. NCI-H146	4.2	CNS cancer (glio) SNB-19	13.3
Lung ca. SHP-77	1.4	CNS cancer (glio) SF-295	21.8
Lung ca. A549	3.8	Brain (Amygdala) Pool	3.8
Lung ca. NCI-H526	5.7	Brain (cerebellum)	4.7
Lung ca. NCI-H23	4.7	Brain (fetal)	1.4
Lung ca. NCI-H460	2.8	Brain (Hippocampus) Pool	4.7
Lung ca. HOP-62	6.7	Cerebral Cortex Pool	6.4
Lung ca. NCI-H522	4.5	Brain (Substantia nigra)	9.3
		Pool
Liver	2.0	Brain (Thalamus) Pool	6.0
Fetal Liver	2.4	Brain (whole)	2.8
Liver ca. HepG2	4.5	Spinal Cord Pool	6.4
Kidney Pool	4.5	Adrenal Gland	3.1
Fetal Kidney	3.2	Pituitary gland Pool	4.3
Renal ca. 786-0	6.7	Salivary Gland	4.6
Renal ca. A498	5.4	Thyroid (female)	6.9
Renal ca. ACHN	3.6	Pancreatic ca. CAPAN2	9.5
Renal ca. UO-31	6.3	Pancreas Pool	6.0

[0729]

TABLE LD
Panel 4.1D
	Rel. Exp. (%) Ag4246,		Rel. Exp. (%) Ag4246,
Tissue Name	Run 175165709	Tissue Name	Run 175165709
Secondary Th1 act	9.5	HUVEC IL-1beta	17.1
Secondary Th2 act	28.9	HUVEC IFN gamma	18.6
Secondary Tr1 act	13.6	HUVEC TNF alpha + IFN	12.2
		gamma
Secondary Th1 rest	12.5	HUVEC TNF alpha + IL4	11.2
Secondary Th2 rest	11.9	HUVEC IL-11	23.0
Secondary Tr1 rest	21.9	Lung Microvascular EC none	40.1
Primary Th1 act	19.8	Lung Microvascular EC	40.6
		TNF alpha + IL-1beta
Primary Th2 act	34.4	Microvascular Dermal EC	26.2
		none
Primary Tr1 act	25.0	Microsvascular Dermal EC	12.9
		TNF alpha + IL-1beta
Primary Th1 rest	11.8	Bronchial epithelium	21.3
		TNF alpha + IL1beta
Primary Th2 rest	11.2	Small airway epithelium none	13.3
Primary Tr1 rest	11.5	Small airway epithelium	43.2
		TNF alpha + IL-1beta
CD45RA CD4	9.4	Coronery artery SMC rest	25.0
lymphocyte act
CD45RO CD4	10.4	Coronery artery SMC	16.5
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	26.4	Astrocytes rest	20.3
Secondary CD8	24.0	Astrocytes TNF alpha + IL-	15.3
lymphocyte rest		1beta
Secondary CD8	22.4	KU-812 (Basophil) rest	10.4
lymphocyte act
CD4 lymphocyte none	13.6	KU-812 (Basophil)	8.4
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	28.9	CCD1106 (Keratinocytes)	28.1
CD95 CH11		none
LAK cells rest	24.1	CCD1106 (Keratinocytes)	20.3
		TNF alpha + IL-1beta
LAK cells IL-2	10.9	Liver cirrhosis	36.3
LAK cells IL-2 + IL-12	14.5	NCI-H292 none	67.4
LAK cells IL-2 + IFN	17.4	NCI-H292-IL4	66.9
gamma
LAK cells IL-2 + IL-18	22.1	NCI-H292 IL-9	74.7
LAK cells	1.4	NCI-H292 IL-13	38.4
PMA/ionomycin
NK Cells IL-2 rest	19.1	NCI-H292 IFN gamma	60.7
Two Way MLR 3 day	33.4	HPAEC none	15.9
Two Way MLR 5 day	14.1	HPAEC TNF alpha + IL-1beta	26.6
Two Way MLR 7 day	22.1	Lung fibroblast none	45.7
PBMC rest	18.0	Lung fibroblast TNF alpha +	55.1
		IL-1beta
PBMC PWM	23.8	Lung fibroblast IL-4	54.3
PBMC PHA-L	21.8	Lung fibroblast IL-9	77.9
Ramos (B cell) none	67.8	Lung fibroblast IL-13	32.1
Ramos (B cell) ionomycin	64.6	Lung fibroblast IFN gamma	32.1
B lymphocytes PWM	8.5	Dermal fibroblast CCD1070	33.0
		rest
B lymphocytes CD40L	17.0	Dermal fibroblast CCD1070	15.3
and IL-4		TNF alpha
EOL-1 dbcAMP	27.4	Dermal fibroblast CCD1070	12.2
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	24.8
PMA/ionomycin
Dendritic cells none	50.0	Dermal fibroblast IL-4	27.4
Dendritic cells LPS	36.9	Dermal fibroblast rest	38.2
Dendritic cells anti-CD40	40.1	Neutrophils TNFa + LPS	0.0
Monocytes rest	37.1	Neutrophils rest	9.2
Monocytes LPS	4.7	Colon	23.7
Macrophages rest	37.9	Lung	16.2
Macrophages LPS	27.2	Thymus	39.5
HUVEC none	20.2	Kidney	100.0
HUVEC starved	19.2

[0730]

TABLE LE
general oncology screening panel_v_2.4
	Rel. Exp. (%) Ag4246, Run		Rel. Exp. (%) Ag4246, Run
Tissue Name	268664320	Tissue Name	268664320
Colon cancer 1	63.7	Bladder cancer NAT 2	2.4
Colon cancer NAT 1	33.4	Bladder cancer NAT 3	1.7
Colon cancer 2	17.8	Bladder cancer NAT 4	16.3
Colon cancer NAT 2	23.3	Adenocarcinoma of the	23.8
		prostate 1
Colon cancer 3	82.4	Adenocarcinoma of the	11.2
		prostate 2
Colon cancer NAT 3	39.8	Adenocarcinoma of the	38.2
		prostate 3
Colon malignant	50.3	Adenocarcinoma of the	25.3
cancer 4		prostate 4
Colon normal adjacent	10.2	Prostate cancer NAT 5	15.8
tissue 4
Lung cancer 1	26.1	Adenocarcinoma of the	12.9
		prostate 6
Lung NAT 1	1.9	Adenocarcinoma of the	16.4
		prostate 7
Lung cancer 2	74.7	Adenocarcinoma of the	2.9
		prostate 8
Lung NAT 2	5.1	Adenocarcinoma of the	33.7
		prostate 9
Squamous cell	25.7	Prostate cancer NAT 10	14.9
carcinoma 3
Lung NAT 3	1.9	Kidney cancer 1	49.7
metastatic melanoma 1	22.5	KidneyNAT 1	23.3
Melanoma 2	6.6	Kidney cancer 2	87.1
Melanoma 3	2.8	Kidney NAT 2	90.1
metastatic melanoma 4	45.7	Kidney cancer 3	90.8
metastatic melanoma 5	43.8	Kidney NAT 3	20.3
Bladder cancer 1	0.4	Kidney cancer 4	100.0
Bladder cancer NAT 1	0.0	Kidney NAT 4	63.7
Bladder cancer 2	11.6

[0731] CNS_neurodegeneration_v1.0 Summary: Ag4246 This panel confirms the expression of the CG102878-01 gene at low levels in the brain in an independent group of individuals. This gene is found to be down-regulated in the temporal cortex of Alzheimer's disease patients. Therefore, up-regulation of this gene or its protein product, or treatment with specific agonists for this receptor may be of use in reversing the dementia/memory loss associated with this disease and neuronal death.

[0732] General_screening_panel_v1.4 Summary: Ag4246 Highest expression of the CG102878-01 gene is detected in breast cancer T47D cell line (CT=26.2). Significant expression of this gene is also seen in clusters of cancer cell lines derived from melanoma, pancreatic, renal, gastric, colon, lung, breast, ovarian and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of gastric, colon, lung, breast, ovarian and brain cancer.

[0733] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0734] 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, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0735] Panel 4.1D Summary: Ag4246 Highest expression of the CG102878-01 gene is detected in kidney (CT=31.9). This gene is expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0736] general oncology screening panel_v—2.4 Summary: Ag4246 Highest expression of the CG02878-01 gene is detected in kidney cancer sample (CT=31). Moderate to low levels of expression of this gene is seen in normal and cancer samples derived from kidney, colon, lung, and prostate. Significant expression of this gene is also seen in metastatic melanoma. Interestingly, expression of this gene is higher in lung cancer samples as compared to adjacent control samples. Therefore, expression of this gene may be used as diagnostic marker for lung cancer and metastic melanoma. Furtherermore, therapeutic modulation of this gene product may be beneficial in the treatment of melanoma, colon, lung, prostate and some cases of kidney cancer.

[0737] M. CG103459-01: Novel Peptide/Histidine Transporter

[0738] Expression of gene CG103459-01 was assessed using the primer-probe set Ag4262, described in Table MA. Results of the RTQ-PCR runs are shown in Tables MB, MC and MD.

TABLE MA
Probe Name Ag4262
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cagagtaatggtgaaggcattg-3′	22	845	186
Probe	TET-′-tcagcaatcttctaaacaagtctgtttga-3′-TAMRA	30	874	187
Reverse	5′-cccaccatgagacatcttacat-3′	22	907	188

[0739]

TABLE MB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%) Ag4262, Run		Rel. Exp. (%) Ag4262, Run
Tissue Name	224076196	Tissue Name	224076196
AD 1 Hippo	6.8	Control (Path) 3	3.5
		Temporal Ctx
AD 2 Hippo	18.8	Control (Path) 4	15.3
		Temporal Ctx
AD 3 Hippo	6.7	AD 1 Occipital Ctx	11.0
AD 4 Hippo	10.2	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	32.8	AD 3 Occipital Ctx	4.9
AD 6 Hippo	100.0	AD 4 Occipital Ctx	12.2
Control 2 Hippo	17.6	AD 5 Occipital Ctx	20.0
Control 4 Hippo	42.0	AD 6 Occipital Ctx	32.3
Control (Path) 3 Hippo	20.6	Control 1 Occipital Ctx	3.6
AD 1 Temporal Ctx	10.7	Control 2 Occipital Ctx	29.1
AD 2 Temporal Ctx	19.5	Control 3 Occipital Ctx	8.2
AD 3 Temporal Ctx	4.0	Control 4 Occipital Ctx	7.4
AD 4 Temporal Ctx	14.4	Control (Path) 1	27.4
		Occipital Ctx
AD 5 Inf Temporal Ctx	42.9	Control (Path) 2	6.0
		Occipital Ctx
AD 5 Sup Temporal	68.8	Control (Path) 3	4.1
Ctx		Occipital Ctx
AD 6 Inf Temporal Ctx	72.7	Control (Path) 4	9.9
		Occipital Ctx
AD 6 Sup Temporal	68.8	Control 1 Parietal Ctx	4.7
Ctx
Control 1 Temporal	7.7	Control 2 Parietal Ctx	33.2
Ctx
Control 2 Temporal	16.8	Control 3 Parietal Ctx	9.0
Ctx
Control 3 Temporal	9.4	Control (Path) 1	27.0
Ctx		Parietal Ctx
Control 3 Temporal	9.5	Control (Path) 2	12.6
Ctx		Parietal Ctx
Control (Path) 1	25.9	Control (Path) 3	4.3
Temporal Ctx		Parietal Ctx
Control (Path) 2	15.6	Control (Path) 4	14.8
Temporal Ctx		Parietal Ctx

[0740]

TABLE MC
General_screening_panel_v1.4
	Rel. Exp. (%) Ag4262,		Rel. Exp. (%) Ag4262,
Tissue Name	Run 222046622	Tissue Name	Run 222046622
Adipose	8.0	Renal ca. TK-10	34.2
Melanoma*	35.4	Bladder	15.8
Hs688(A).T
Melanoma*	41.2	Gastric ca. (liver met.)	20.6
Hs688(B).T		NCI-N87
Melanoma* M14	97.9	Gastric ca. KATO III	36.3
Melanoma* LOXIMVI	37.9	Colon ca. SW-948	13.4
Melanoma* SK-MEL-5	40.9	Colon ca. SW480	40.9
Squamous cell	10.2	Colon ca.* (SW480 met)	19.9
carcinoma SCC-4		SW620
Testis Pool	16.6	Colon ca. HT29	15.9
Prostate ca.* (bone met)	44.8	Colon ca. HCT-116	47.6
PC-3
Prostate Pool	5.3	Colon ca. CaCo-2	20.6
Placenta	8.2	Colon cancer tissue	36.3
Uterus Pool	7.5	Colon ca. SW1116	2.8
Ovarian ca. OVCAR-3	26.2	Colon ca. Colo-205	9.9
Ovarian ca. SK-OV-3	55.9	Colon ca. SW-48	8.8
Ovarian ca. OVCAR-4	6.5	Colon Pool	18.8
Ovarian ca. OVCAR-5	34.9	Small Intestine Pool	12.2
Ovarian ca. IGROV-1	25.3	Stomach Pool	9.4
Ovarian ca. OVCAR-8	20.0	Bone Marrow Pool	8.4
Ovary	9.0	Fetal Heart	5.0
Breast ca. MCF-7	27.0	Heart Pool	7.5
Breast ca. MDA-MB-	46.3	Lymph Node Pool	26.4
231
Breast ca. BT 549	63.7	Fetal Skeletal Muscle	7.5
Breast ca. T47D	78.5	Skeletal Muscle Pool	17.0
Breast ca. MDA-N	23.3	Spleen Pool	9.6
Breast Pool	19.2	Thymus Pool	14.7
Trachea	12.9	CNS cancer (glio/astro)	57.8
		U87-MG
Lung	2.0	CNS cancer (glio/astro) U-	65.5
		118-MG
Fetal Lung	19.8	CNS cancer (neuro; met)	33.4
		SK-N-AS
Lung ca. NCI-N417	3.6	CNS cancer (astro) SF-539	30.6
Lung ca. LX-1	25.9	CNS cancer (astro) SNB-	100.0
		75
Lung ca. NCI-H146	7.6	CNS cancer (glio) SNB-19	23.2
Lung ca. SHP-77	17.7	CNS cancer (glio) SF-295	47.3
Lung ca. A549	44.1	Brain (Amygdala) Pool	6.2
Lung ca. NCI-H526	7.4	Brain (cerebellum)	12.1
Lung ca. NCI-H23	33.7	Brain (fetal)	6.7
Lung ca. NCI-H460	22.7	Brain (Hippocampus) Pool	8.8
Lung ca. HOP-62	25.5	Cerebral Cortex Pool	7.5
Lung ca. NCI-H522	31.4	Brain (Substantia nigra)	7.6
		Pool
Liver	4.4	Brain (Thalamus) Pool	9.8
Fetal Liver	17.8	Brain (whole)	9.4
Liver ca. HepG2	19.3	Spinal Cord Pool	13.2
Kidney Pool	26.2	Adrenal Gland	9.7
Fetal Kidney	9.5	Pituitary gland Pool	3.7
Renal ca. 786-0	69.3	Salivary Gland	6.1
Renal ca. A498	20.6	Thyroid (female)	8.2
Renal ca. ACHN	38.4	Pancreatic ca. CAPAN2	31.4
Renal ca. UO-31	94.0	Pancreas Pool	45.7

[0741]

TABLE MD
Panel 4.1D
	Rel. Exp. (%) Ag4262,		Rel. Exp. (%) Ag4262,
Tissue Name	Run 176243568	Tissue Name	Run 176243568
Secondary Th1 act	37.1	HUVEC IL-1beta	28.9
Secondary Th2 act	30.4	HUVEC IFN gamma	18.0
Secondary Tr1 act	14.1	HUVEC TNF alpha + IFN	34.9
		gamma
Secondary Th1 rest	9.0	HUVEC TNF alpha + IL4	28.5
Secondary Th2 rest	6.4	HUVEC IL-11	8.4
Secondary Tr1 rest	7.4	Lung Microvascular EC none	27.7
Primary Th1 act	14.7	Lung Microvascular EC	28.3
		TNF alpha + IL-1beta
Primary Th2 act	17.4	Microvascular Dermal EC	16.0
		none
Primary Tr1 act	22.5	Microsvasular Dermal EC	18.9
		TNF alpha + IL-1beta
Primary Th1 rest	5.6	Bronchial epithelium	39.8
		TNF alpha + IL1beta
Primary Th2 rest	2.5	Small airway epithelium none	14.6
Primary Tr1 rest	13.5	Small airway epithelium	47.0
		TNF alpha + IL-1beta
CD45RA CD4	40.1	Coronery artery SMC rest	20.9
lymphocyte act
CD45RO CD4	33.7	Coronery artery SMC	25.9
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	31.6	Astrocytes rest	22.5
Secondary CD8	20.4	Astrocytes TNF alpha + IL-	22.2
lymphocyte rest		1beta
Secondary CD8	9.7	KU-812 (Basophil) rest	14.0
lymphocyte act
CD4 lymphocyte none	7.0	KU-812 (Basophil)	16.7
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	12.3	CCD1106 (Keratinocytes)	44.8
CD95 CH11		none
LAK cells rest	46.0	CCD1106 (Keratinocytes)	27.4
		TNF alpha + IL-1beta
LAK cells IL-2	28.9	Liver cirrhosis	7.5
LAK cells IL-2 + IL-12	18.2	NCI-H292 none	18.0
LAK cells IL-2 + IFN	21.8	NCI-H292 IL-4	24.0
gamma
LAK cells IL-2 + IL-18	34.2	NCI-H292 IL-9	33.2
LAK cells	26.8	NCI-H292 IL-13	27.5
PMA/ionomycin
NK Cells IL-2 rest	71.7	NCI-H292 IFN gamma	20.6
Two Way MLR 3 day	41.5	HPAEC none	13.0
Two Way MLR 5 day	41.5	HPAEC TNF alpha + IL-1beta	41.2
Two Way MLR 7 day	25.9	Lung fibroblast none	27.7
PBMC rest	15.3	Lung fibroblast TNF alpha +	29.3
		IL-1beta
PBMC PWM	27.0	Lung fibroblast IL-4	24.7
PBMC PHA-L	43.8	Lung fibroblast IL-9	34.9
Ramos (B cell) none	32.3	Lung fibroblast IL-13	24.5
Ramos (B cell) ionomycin	51.1	Lung fibroblast IFN gamma	52.1
B lymphocytes PWM	28.3	Dermal fibroblast CCD1070	31.6
		rest
B lymphocytes CD40L	66.4	Dermal fibroblast CCD1070	45.1
and IL-4		TNF alpha
EOL-1 dbcAMP	17.3	Dermal fibroblast CCD1070	28.1
		IL-1beta
EOL-1 dbcAMP	18.2	Dermal fibroblast IFN gamma	28.1
PMA/ionomycin
Dendritic cells none	44.8	Dermal fibroblast IL-4	38.7
Dendritic cells LPS	36.1	Dermal Fibroblasts rest	22.5
Dendritic cells anti-CD40	42.9	Neutrophils TNFa + LPS	56.6
Monocytes rest	49.0	Neutrophils rest	100.0
Monocytes LPS	47.6	Colon	9.4
Macrophages rest	52.9	Lung	16.4
Macrophages LPS	21.9	Thymus	23.8
HUVEC none	9.9	Kidney	15.2
HUVEC starved	21.2

[0742] CNS_neurodegeneration_v1.0 Summary: Ag4262 This panel confirms the expression of the CG103459-01 gene at low levels in the brains of an independent group of individuals.

[0743] However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential use of this gene in treatment of central nervous system disorders.

[0744] General_screening_panel_v1.4 Summary: Ag4262 Highest expression of the CG103459-01 gene is detected in CNS cancer (astro) SNB-75 cell line (28.7). High to moderate levels of expression of this gene is seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, renal, lung, breast, ovarian, prostate, squamous cell carcinoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.

[0745] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0746] 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, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0747] Panel 4.1D Summary: Ag4262 Highest expression of the CG103459-01 gene is detected in resting neutrophils (CT=29.3). This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0748] N. CG104210-01: Type III Membrane Protein

[0749] Expression of gene CG104210-01 was assessed using the primer-probe set Ag4270, described in Table NA. Results of the RTQ-PCR runs are shown in Tables NB, NC, ND and NE.

TABLE NA
Probe Name Ag4270
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-acctgcagctgagaaaatcc-3′	20	1250	189
Probe	TET-5′-ctcaaccacctcgtctcctccatcg-3′-TAMRA	25	2270	190
Reverse	5′-aggcatacaacccactgtca-3′	20	1316	191

[0750]

TABLE NB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%) Ag4270, Run		Rel. Exp. (%) Ag4270, Run
Tissue Name	224075728	Tissue Name	224075728
AD 1 Hippo	69.7	Control (Path) 3	0.0
		Temporal Ctx
AD 2 Hippo	36.9	Control (Path) 4	0.0
		Temporal Ctx
AD 3 Hippo	0.0	AD 1 Occipital Ctx	0.0
AD 4 Hippo	0.0	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	0.0	AD 3 Occipital Ctx	0.0
AD 6 Hippo	0.0	AD 4 Occipital Ctx	27.7
Control 2 Hippo	20.7	AD 5 Occipital Ctx	0.0
Control 4 Hippo	100.0	AD 6 Occipital Ctx	22.2
Control (Path) 3 Hippo	37.9	Control 1 Occipital Ctx	17.3
AD 1 Temporal Ctx	0.0	Control 2 Occipital Ctx	21.6
AD 2 Temporal Ctx	0.0	Control 3 Occipital Ctx	36.9
AD 3 Temporal Ctx	0.0	Control 4 Occipital Ctx	0.0
AD 4 Temporal Ctx	35.6	Control (Path) 1	34.4
		Occipital Ctx
AD 5 Inf Temporal Ctx	0.0	Control (Path) 2	0.0
		Occipital Ctx
AD 5 Sup Temporal	30.6	Control (Path) 3	0.0
Ctx		Occipital Ctx
AD 6 Inf Temporal Ctx	37.1	Control (Path) 4	0.0
		Occipital Ctx
AD 6 Sup Temporal	73.7	Control 1 Parietal Ctx	0.0
Ctx
Control 1 Temporal	11.9	Control 2 Parietal Ctx	18.2
Ctx
Control 2 Temporal	0.0	Control 3 Parietal Ctx	0.0
Ctx
Control 3 Temporal	17.1	Control (Path) 1	11.3
Ctx		Parietal Ctx
Control 3 Temporal	0.0	Control (Path) 2	14.5
Ctx		Parietal Ctx
Control (Path) 1	41.5	Control (Path) 3	0.0
Temporal Ctx		Parietal Ctx
Control (Path) 2	0.0	Control (Path) 4	49.3
Temporal Ctx		Parietal Ctx

[0751]

TABLE NC
HASS Panel v1.0
Tissue	Rel. Exp. (%) Ag4270, Run		Rel. Exp. (%) Ag4270, Run
Name	268623848	Tissue Name	268623848
MCF-7 C1	13.7	U87-MG F1 (B)	0.0
MCF-7 C2	18.4	U87-MG F2	0.0
MCF-7 C3	8.7	U87-MG F3	2.4
MCF-7 C4	22.5	U87-MG F4	0.0
MCF-7 C5	9.9	U87-MG F5	0.0
MCF-7 C6	12.6	U87-MG F6	0.0
MCF-7 C7	29.9	U87-MG F7	0.0
MCF-7 C9	8.7	U87-MG F8	0.0
MCF-7	29.9	U87-MG F9	0.0
C10
MCF-7	2.7	U87-MG F10	0.0
C11
MCF-7	12.7	U87-MG F11	0.0
C12
MCF-7	40.3	U87-MG F12	0.0
C13
MCF-7	10.1	U87-MG F13	0.0
C15
MCF-7	10.1	U87-MG F14	1.3
C16
MCF-7	15.0	U87-MG F15	0.0
C17
T24 D1	0.0	U87-MG F16	0.0
T24 D2	0.0	U87-MG F17	0.0
T24 D3	0.0	LnCAP A1	60.3
T24 D4	0.0	LnCAP A2	40.1
T24 D5	0.0	LnCAP A3	74.2
T24 D6	0.0	LnCAP A4	26.1
T24 D7	0.0	LnCAP A5	33.0
T24 D9	0.0	LnCAP A6	23.0
T24 D10	0.0	LnCAP A7	68.3
T24 D11	0.0	LnCAP A8	69.7
T24 D12	0.0	LnCAP A9	38.4
T24 D13	0.0	LnCAP A10	62.0
T24 D15	0.0	LnCAP A11	100.0
T24 D16	0.0	LnCAP A12	13.2
T24 D17	0.0	LnCAP A13	51.4
CAPaN B1	39.0	LnCAP A14	30.1
CAPaN B2	16.8	LnCAP A15	22.5
CAPaN B3	17.7	LnCAP A16	48.0
CAPaN B4	16.8	LnCAP A17	70.2
CAPaN B5	26.6	Primary Astrocytes	0.0
CAPaN B6	5.7	Primary Renal Proximal Tubule	0.0
		Epithelial cell A2
CAPaN B7	24.3	Primary melanocytes A5	0.0
CAPaN B8	27.2	126443-341 medullo	4.2
CAPaN B9	18.3	126444-487 medullo	0.0
CAPaN	67.8	126445-425 medullo	0.0
B10
CAPaN	81.8	126446-690 medullo	1.3
B11
CAPaN	23.0	126447-54 adult glioma	0.0
B12
CAPaN	71.2	126448-245 adult glioma	0.0
B13
CAPaN	27.9	126449-317 adult glioma	0.0
B14
CAPaN	14.8	126450-212 glioma	0.0
B15
CAPaN	17.4	126451-456 glioma	0.0
B16
CAPaN	48.3
B17

[0752]

TABLE ND
Panel 4.1D
	Rel. Exp. (%) Ag4270,		Rel. Exp. (%) Ag4270,
Tissue Name	Run 181080817	Tissue Name	Run 181080817
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.4	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.5
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvascular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	1.3
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	2.0
Primary Tr1 rest	0.0	Small airway epithelium	6.2
		TNF alpha + IL-1beta
CD45RA CD4	100.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha + IL-	0.0
lymphocyte rest		1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	1.5
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.9
		TNF alpha + IL-1beta
LAK cells IL-2	0.4	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.8
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	0.5
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	1.6
LAK cells	5.8	NCI-H292 IL-13	0.5
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.3
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.5	HPAEC TNF alpha + IL-1beta	0.0
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha +	0.0
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070	0.0
		rest
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070	0.0
and IL-4		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	0.0
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblast rest	0.7
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.5
Monocytes rest	0.0	Neutrophils rest	0.5
Monocytes LPS	1.2	Colon	0.0
Macrophages rest	0.0	Lung	1.6
Macrophages LPS	0.0	Thymus	4.1
HUVEC none	0.0	Kidney	30.1
HUVEC starved	0.0

[0753]

TABLE NE
general oncology screening panel_v_2.4
	Rel. Exp. (%) Ag4270, Run		Rel. Exp. (%) Ag4270, Run
Tissue Name	260280401	Tissue Name	260280401
Colon cancer 1	3.8	Bladder cancer NAT 2	0.0
Colon cancer NAT 1	0.0	Bladder cancer NAT 3	0.0
Colon cancer 2	10.4	Bladder cancer NAT 4	0.0
Colon cancer NAT 2	0.0	Adenocarcinoma of the	4.3
		prostate 1
Colon cancer 3	3.3	Adenocarcinoma of the	11.1
		prostate 2
Colon cancer NAT 3	0.0	Adenocarcinoma of the	36.3
		prostate 3
Colon malignant	2.0	Adenocarcinoma of the	9.9
cancer 4		prostate 4
Colon normal adjacent	0.0	Prostate cancer NAT 5	73.7
tissue 4
Lung cancer 1	82.9	Adenocarcinoma of the	12.1
		prostate 6
Lung NAT 1	11.5	Adenocarcinoma of the	9.9
		prostate 7
Lung cancer 2	9.3	Adenocarcinoma of the	4.0
		prostate 8
Lung NAT 2	3.3	Adenocarcinoma of the	18.3
		prostate 9
Squamous cell	33.7	Prostate cancer NAT 10	1.8
carcinoma 3
Lung NAT 3	15.0	Kidney cancer 1	0.0
metastatic melanoma 1	100.0	KidneyNAT 1	1.9
Melanoma 2	81.8	Kidney cancer 2	2.1
Melanoma 3	81.8	Kidney NAT 2	2.1
metastatic melanoma 4	0.0	Kidney cancer 3	0.0
metastatic melanoma 5	2.2	Kidney NAT 3	0.0
Bladder cancer 1	0.0	Kidney cancer 4	0.0
Bladder cancer NAT 1	0.0	Kidney NAT 4	0.0
Bladder cancer 2	0.0

[0754] CNS_neurodegeneration_v1.0 Summary: Ag4270 This panel confirms the expression of the CG104210-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Low expression of this gene in brain suggests that this gene may play role in neurological disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Therefore, therapeutic modulation of this gene may be useful in the treatment of these neurological disorders.

[0755] HASS Panel v1.0 Summary: Ag4270 Highest expression of the CG104210-01 gene is detected in LnCAP (A11) cell line sample (CT=31.6) that are exposed to an acidic environment. CaPAN cells also show a modest increase in gene expression when exposed to an acidic environment (A10, A11 compared to A4, A5 resp.)

[0756] This suggests a possible induction of this gene in acidotic regions of prostate and pancreatic cancer.

[0757] Panel 4.1D Summary: Ag4270 Highest expression of the CG104210-01 gene is detected in activated CD45RA CD4 lymphocyte (CT=29), which represent activated naive T cells. In activated memory T cells (CD45RO CD4 lymphocyte) or CD4 Th1 or Th2 cells, resting CD4 cells (CTs=40), the expression of CG104210-01 is strongly down regulated suggesting a role for this putative protein in differentiation or activation of naive T cells. Therefore, expression of this gene may be used to distinguish this sample from other samples used in this panel. In addition, Therefore modulation of the expression and/or activity of this putative protein encoded by this gene might be beneficial for the control of autoimmune diseases and T cell mediated diseases such as arthritis, psoriasis, IBD and asthma.

[0758] Furthermore, low expression of this gene is also seen in small airway epithelium, and PMA/ionomycin treated LAK cells. In addition, moderate expression of this gene is also seen in kidney and thymus. Therefore, therapeutic modulation of this gene product may be useful in the treatment of autoimmune and inflammatory diseases involving these cell and tissue types such as asthma, COPD, arthritis, psoriasis, IBD, lupus, viral and bacterial infection.

[0759] general oncology screening panel_v—2.4 Summary: Ag4270 Highest expression of the CG104210-01 gene is detected in metastatic melanoma (CT=33). Significant expression of this gene is also seen in melanoma and a lung cancer (OD06850-03C) samples. Interestingly, expression of this gene in lung cancer is higher as compared to the adjacent control sample. Therefore, expression of this gene may be used as diagnostic marker for detection of melanoma and lung cancer. Furthermore, therapeutic modulation of this gene may be useful in the treatment of melanoma and lung cancer.

[0760] O. CG104251-01: Type III Membrane Protein

[0761] Expression of gene CG104251-01 was assessed using the primer-probe set Ag4280, described in Table OA. Results of the RTQ-PCR runs are shown in Tables OB, OC and OD.

TABLE OA
Probe Name Ag4280
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cctttatgcaaccaacatgg-3′	20	7	192
Probe	TET-5′-ccatgtcctgttcttagtgcttgaatgtcc-3′TAMRA	30	37	193
Reverse	5′-ggcttcttcagcttcaggtt-3′	20	68	194

[0762]

TABLE OB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%) Ag4280, Run		Rel. Exp. (%) Ag4280, Run
Tissue Name	224075293	Tissue Name	224075293
AD 1 Hippo	11.3	Control (Path) 3	3.5
		Temporal Ctx
AD 2 Hippo	18.6	Control (Path) 4	15.3
		Temporal Ctx
AD 3 Hippo	7.9	AD 1 Occipital Ctx	6.0
AD 4 Hippo	6.9	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	54.3	AD 3 Occipital Ctx	5.3
AD 6 Hippo	100.0	AD 4 Occipital Ctx	5.9
Control 2 Hippo	14.8	AD 5 Occipital Ctx	7.4
Control 4 Hippo	13.6	AD 6 Occipital Ctx	33.9
Control (Path) 3 Hippo	9.9	Control 1 Occipital	2.6
		Ctx
AD 1 Temporal Ctx	10.8	Control 2 Occipital	30.6
		Ctx
AD 2 Temporal Ctx	7.1	Control 3 Occipital	10.4
		Ctx
AD 3 Temporal Ctx	5.5	Control 4 Occipital	6.5
		Ctx
AD 4 Temporal Ctx	7.4	Control (Path) 1	51.4
		Occipital Ctx
AD 5 Inf Temporal Ctx	47.0	Control (Path) 2	13.8
		Occipital Ctx
AD 5 SupTemporal Ctx	37.1	Control (Path) 3	5.2
		Occipital Ctx
AD 6 Inf Temporal Ctx	42.0	Control (Path) 4	12.7
		Occipital Ctx
AD 6 Sup Temporal Ctx	50.0	Control 1 Parietal Ctx	7.2
Control 1 Temporal Ctx	4.4	Control 2 Parietal Ctx	29.1
Control 2 Temporal Ctx	27.0	Control 3 Parietal Ctx	23.3
Control 3 Temporal Ctx	8.8	Control (Path) 1	33.7
		Parietal Ctx
Control 4 Temporal Ctx	2.9	Control (Path) 2	6.6
		Parietal Ctx
Control (Path) 1	44.4	Control (Path) 3	14.2
Temporal Ctx		Parietal Ctx
Control (Path) 2	26.1	Control (Path) 4	16.5
Temporal Ctx		Parietal Ctx

[0763]

TABLE OC
General_screening_panel_v1.4
	Rel. Exp. (%) Ag4280,		Rel. Exp. (%) Ag4280,
Tissue Name	Run 222183179	Tissue Name	Run 222183179
Adipose	3.0	Renal ca. TK-10	60.7
Melanoma*	43.5	Bladder	23.5
Hs688(A).T
Melanoma*	45.1	Gastric ca. (liver met.)	56.6
Hs688(B).T		NCI-N87
Melanoma* M14	23.0	Gastric ca. KATO III	52.9
Melanoma* LOXIMVI	20.0	Colon ca. SW-948	19.3
Melanoma* SK-MEL-5	41.5	Colon ca. SW480	48.3
Squamous cell	21.0	Colon ca.* (SW480 met)	34.4
carcinoma SCC-4		SW620
Testis Pool	6.1	Colon ca. HT29	41.2
Prostate ca.* (bone met)	46.0	Colon ca. HCT-116	100.0
PC-3
Prostate Pool	5.2	Colon ca. CaCo-2	35.4
Placenta	7.5	Colon cancer tissue	30.4
Uterus Pool	1.3	Colon ca. SW1116	13.4
Ovarian ca. OVCAR-3	88.3	Colon ca. Colo-205	15.8
Ovarian ca. SK-OV-3	52.1	Colon ca. SW-48	11.1
Ovarian ca. OVCAR-4	17.7	Colon Pool	4.3
Ovarian ca. OVCAR-5	80.1	Small Intestine Pool	2.6
Ovarian ca. IGROV-1	51.8	Stomach Pool	8.7
Ovarian ca. OVCAR-8	29.3	Bone Marrow Pool	2.0
Ovary	8.4	Fetal Heart	6.4
Breast ca. MCF-7	31.6	Heart Pool	2.1
Breast ca. MDA-MB-	38.4	Lymph Node Pool	7.7
231
Breast ca. BT 549	19.8	Fetal Skeletal Muscle	3.5
Breast ca. T47D	79.6	Skeletal Muscle Pool	3.0
Breast ca. MDA-N	23.3	Spleen Pool	5.4
Breast Pool	8.6	Thymus Pool	11.5
Trachea	13.3	CNS cancer (glio/astro)	55.5
		U87-MG
Lung	3.8	CNS cancer (glio/astro) U-	50.3
		118-MG
Fetal Lung	11.5	CNS cancer (neuro; met)	80.7
		SK-N-AS
Lung ca. NCI-N417	13.1	CNS cancer (astro) SF-539	37.1
Lung ca. LX-1	32.1	CNS cancer (astro) SNB-	61.1
		75
Lung ca. NCI-H146	9.9	CNS cancer (glio) SNB-19	38.7
Lung ca. SHP-77	23.5	CNS cancer (glio) SF-295	47.0
Lung ca. A549	40.1	Brain (Amygdala) Pool	2.3
Lung ca. NCI-H526	8.7	Brain (cerebellum)	2.8
Lung ca. NCI-H23	46.0	Brain (fetal)	3.1
Lung ca. NCI-H460	23.2	Brain (Hippocampus) Pool	1.8
Lung ca. HOP-62	27.7	Cerebral Cortex Pool	1.5
Lung ca. NCI-H522	18.6	Brain (Substantia nigra)	1.9
		Pool
Liver	1.6	Brain (Thalamus) Pool	3.4
Fetal Liver	17.0	Brain (whole)	2.6
Liver ca. HepG2	51.8	Spinal Cord Pool	2.8
Kidney Pool	8.8	Adrenal Gland	6.1
Fetal Kidney	13.2	Pituitary gland Pool	5.2
Renal ca. 786-0	70.2	Salivary Gland	4.4
Renal ca. A498	21.6	Thyroid (female)	7.5
Renal ca. ACHN	15.6	Pancreatic ca. CAPAN2	52.1
Renal ca. UO-31	27.4	Pancreas Pool	13.7

[0764]

TABLE OD
Panel 4.1D
	Rel. Exp. (%) Ag4280,		Rel. Exp. (%) Ag4280,
Tissue Name	Run 176282949	Tissue Name	Run 176282949
Secondary Th1 act	20.6	HUVEC IL-1beta	33.0
Secondary Th2 act	28.5	HUVEC IFN gamma	27.4
Secondary Tr1 act	23.7	HUVEC TNF alpha + IFN	18.2
		gamma
Secondary Th1 rest	2.8	HUVEC TNF alpha + IL4	22.5
Secondary Th2 rest	6.8	HUVEC IL-11	9.8
Secondary Tr1 rest	7.9	Lung Microvascular EC none	33.4
Primary Th1 act	10.3	Lung Microvascular EC	22.8
		TNF alpha + IL-1beta
Primary Th2 act	18.8	Microvascular Dermal EC	13.8
		none
Primary Tr1 act	15.9	Microsvasular Dermal EC	10.7
		TNF alpha + IL-1beta
Primary Th1 rest	3.4	Bronchial epithelium	17.0
		TNF alpha + IL1beta
Primary Th2 rest	3.9	Small airway epithelium none	5.8
Primary Tr1 rest	5.2	Small airway epithelium	8.4
		TNF alpha + IL-1beta
CD45RA CD4	11.2	Coronery artery SMC rest	25.0
lymphocyte act
CD45RO CD4	16.7	Coronery artery SMC	25.9
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	14.6	Astrocytes rest	18.3
Secondary CD8	11.1	Astrocytes TNF alpha + IL-	17.1
lymphocyte rest		1beta
Secondary CD8	5.5	KU-812 (Basophil) rest	19.9
lymphocyte act
CD4 lymphocyte none	1.8	KU-812 (Basophil)	21.6
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	4.9	CCD1106 (Keratinocytes)	14.6
CD95 CH11		none
LAK cells rest	10.2	CCD1106 (Keratinocytes)	15.2
		TNF alpha + IL-1beta
LAK cells IL-2	6.7	Liver cirrhosis	1.1
LAK cells IL-2 + IL-12	9.1	NCI-H292 none	11.8
LAK cells IL-2 + IFN	7.7	NCI-H292 IL-4	15.3
gamma
LAK cells IL-2 + IL-18	8.3	NCI-H292 IL-9	14.4
LAK cells	11.2	NCI-H292 IL-13	14.8
PMA/ionomycin
NK Cells IL-2 rest	9.4	NCI-H292 IFN gamma	11.7
Two Way MLR 3 day	8.6	HPAEC none	12.5
Two Way MLR 5 day	7.3	HPAEC TNF alpha + IL-1beta	42.9
Two Way MLR 7 day	8.0	Lung fibroblast none	10.7
PBMC rest	2.0	Lung fibroblast TNF alpha +	12.3
		IL-1beta
PBMC PWM	9.5	Lung fibroblast IL-4	14.4
PBMC PHA-L	5.0	Lung fibroblast IL-9	18.4
Ramos (B cell) none	21.6	Lung fibroblast IL-13	15.4
Ramos (B cell) ionomycin	28.3	Lung fibroblast IFN gamma	26.2
B lymphocytes PWM	6.0	Dermal fibroblast CCD1070	31.4
		rest
B lymphocytes CD40L	8.8	Dermal fibroblast CCD1070	31.9
and IL-4		TNF alpha
EOL-1 dbcAMP	10.6	Dermal fibroblast CCD1070	26.2
		IL-1beta
EOL-1 dbcAMP	12.7	Dermal fibroblast IFN gamma	18.2
PMA/ionomycin
Dendritic cells none	8.9	Dermal fibroblast IL-4	20.7
Dendritic cells LPS	5.9	Dermal fibroblast rest	10.4
Dendritic cells anti-CD40	7.6	Neutrophils TNFa + LPS	1.8
Monocytes rest	5.3	Neutrophils rest	2.6
Monocytes LPS	10.8	Colon	7.7
Macrophages rest	10.2	Lung	12.2
Macrophages LPS	2.7	Thymus	21.6
HUVEC none	16.0	Kidney	100.0
HUVEC starved	26.6

[0765] CNS_neurodegeneration_v1.0 Summary: Ag4280 Very low levels of expression of the CG104251-01 gene is seen in the brains of an independent group of individuals, with highest expression in hippocampus of an Alzeimer patient (CT=34.3). However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential use of this gene in treatment of central nervous system disorders.

[0766] General_screening_panel_v1.4 Summary: Ag4280 Highest expression of the CG104251-01 gene is detected in a colon cancer HCT-116 cell line (CT=30). Significant expression of this gene is also seen in clusters of cancer cell lines derived from pancreatic, gastric, colon, renal, lung, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene may be useful as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene product may be effective in the treatment of these cancers.

[0767] Among tissues with metabolic or endocrine function, this gene is expressed at low levels in pancreas, adrenal gland, thyroid, pituitary gland, fetal skeletal muscle, heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0768] Interestingly, this gene is expressed at much higher levels in fetal (CT=32.7) when compared to adult liver (CT=36). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver. In addition, the relative overexpression of this gene in fetal liver suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.

[0769] In addition, low expression of this gene is also seen in brain (thalamus). Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of neurological disorders.

[0770] Panel 4.1D Summary: Ag4280 Highest expression of the CG104251-01 gene is detected in kidney (CT=31.8). This gene is expressed at low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, and endothelial cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by lung, thymus and kidney. This pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0771] P. CG104934-01: Potential Phospholipid-Transporting ATPase IH

[0772] Expression of gene CG104934-01 was assessed using the primer-probe set Ag4274, described in Table PA. Results of the RTQ-PCR runs are shown in Tables PB, PC and PD.

TABLE PA
Probe Name Ag4274
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgcttcatcttccctcagttt-3′	21	2734	195
Probe	TET-5′-acaacagactttgtacgacaccgcgt-3′-TAMRA	26	2781	196
Reverse	5′-gctgatgttgtagagggtcaga-3′	22	2808	197

[0773]

TABLE PB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%) Ag4274, Run		Rel. Exp. (%) Ag4274, Run
Tissue Name	224075762	Tissue Name	224075762
AD 1 Hippo	24.5	Control (Path) 3	6.9
		Temporal Ctx
AD 2 Hippo	39.5	Control (Path) 4	27.5
		Temporal Ctx
AD 3 Hippo	11.1	AD 1 Occipital Ctx	27.5
AD 4 Hippo	9.3	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	86.5	AD 3 Occipital Ctx	13.2
AD 6 Hippo	71.2	AD 4 Occipital Ctx	16.0
Control 2 Hippo	27.9	AD 5 Occipital Ctx	31.4
Control 4 Hippo	17.4	AD 6 Occipital Ctx	35.1
Control (Path) 3 Hippo	13.6	Control 1 Occipital Ctx	0.0
AD 1 Temporal Ctx	42.6	Control 2 Occipital Ctx	50.3
AD 2 Temporal Ctx	34.6	Control 3 Occipital Ctx	39.2
AD 3 Temporal Ctx	12.5	Control 4 Occipital Ctx	13.2
AD 4 Temporal Ctx	36.1	Control (Path) 1	100.0
		Occipital Ctx
AD 5 Inf Temporal Ctx	77.9	Control (Path) 2	21.6
		Occipital Ctx
AD 5 Sup Temporal	48.0	Control (Path) 3	12.3
Ctx		Occipital Ctx
AD 6 Inf Temporal Ctx	97.9	Control (Path) 4	22.2
		Occipital Ctx
AD 6 Sup Temporal	66.0	Control 1 Parietal Ctx	10.5
Ctx
Control 1 Temporal	7.7	Control 2 Parietal Ctx	47.0
Ctx
Control 2 Temporal	25.7	Control 3 Parietal Ctx	24.7
Ctx
Control 3 Temporal	21.6	Control (Path) 1	53.2
Ctx		Parietal Ctx
Control 3 Temporal	10.6	Control (Path) 2	25.0
Ctx		Parietal Ctx
Control (Path) 1	42.0	Control (Path) 3	12.3
Temporal Ctx		Parietal Ctx
Control (Path) 2	29.3	Control (Path) 4	40.6
Temporal Ctx		Parietal Ctx

[0774]

TABLE PC
General_screening_panel_v1.4
	Rel. Exp. (%) Ag4274,		Rel. Exp. (%) Ag4274,
Tissue Name	Run 222182089	Tissue Name	Run 222182089
Adipose	4.8	Renal ca. TK-10	44.8
Melanoma*	4.1	Bladder	14.5
Hs688(A).T
Melanoma*	6.0	Gastric ca. (liver met.)	18.9
Hs688(B).T		NCI-N87
Melanoma* M14	27.5	Gastric ca. KATO III	64.6
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	6.4
Melanoma* SK-MEL-5	33.2	Colon ca. SW480	25.3
Squamous cell	9.2	Colon ca.* (SW480 met)	26.6
carcinoma SCC-4		SW620
Testis Pool	7.4	Colon ca. HT29	10.1
Prostate ca.* (bone met)	20.2	Colon ca. HCT-116	26.2
PC-3
Prostate Pool	2.1	Colon ca. CaCo-2	44.1
Placenta	7.9	Colon cancer tissue	20.9
Uterus Pool	3.6	Colon ca. SW1116	4.0
Ovarian ca. OVCAR-3	15.8	Colon ca. Colo-205	20.9
Ovarian ca. SK-OV-3	38.7	Colon ca. SW-48	8.1
Ovarian ca. OVCAR-4	14.0	Colon Pool	14.3
Ovarian ca. OVCAR-5	19.3	Small Intestine Pool	8.8
Ovarian ca. IGROV-1	9.3	Stomach Pool	5.9
Ovarian ca. OVCAR-8	4.1	Bone Marrow Pool	3.5
Ovary	5.4	Fetal Heart	15.8
Breast ca. MCF-7	8.0	Heart Pool	8.4
Breast ca. MDA-MB-	17.8	Lymph Node Pool	14.0
231
Breast ca. BT 549	20.7	Fetal Skeletal Muscle	3.1
Breast ca. T47D	28.5	Skeletal Muscle Pool	6.1
Breast ca. MDA-N	0.0	Spleen Pool	7.0
Breast Pool	15.2	Thymus pool	8.8
Trachea	6.5	CNS cancer (glio/astro)	1.0
		U87-MG
Lung	1.5	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	100.0	CNS cancer (neuro; met)	4.6
		SK-N-AS
Lung ca. NCI-N417	2.2	CNS cancer (astro) SF-539	3.8
Lung ca. LX-1	48.6	CNS cancer (astro) SNB-	15.1
		75
Lung ca. NCI-H146	7.7	CNS cancer (glio) SNB-19	11.1
Lung ca. SHP-77	17.4	CNS cancer (glio) SF-295	10.4
Lung ca. A549	10.8	Brain (Amygdala) Pool	5.6
Lung ca. NCI-H526	3.7	Brain (cerebellum)	10.4
Lung ca. NCI-H23	12.8	Brain (fetal)	6.3
Lung ca. NCI-H460	12.5	Brain (Hippocampus) Pool	5.6
Lung ca. HOP-62	4.0	Cerebral Cortex Pool	7.1
Lung ca. NCI-H522	5.8	Brain (Substantia nigra)	6.2
		Pool
Liver	2.0	Brain (Thalamus) Pool	6.9
Fetal Liver	10.7	Brain (whole)	7.5
Liver ca. HepG2	18.6	Spinal Cord Pool	10.2
Kidney Pool	12.8	Adrenal Gland	13.2
Fetal Kidney	11.1	Pituitary gland Pool	6.1
Renal ca. 786-0	17.0	Salivary Gland	2.7
Renal ca. A498	11.6	Thyroid (female)	3.2
Renal ca. ACHN	12.2	Pancreatic ca. CAPAN2	26.1
Renal ca. UO-31	10.2	Pancreas Pool	22.5

[0775]

TABLE PD
Panel 4.1D
	Rel. Exp. (%) Ag4274,		Rel. Exp. (%) Ag4274,
Tissue Name	Run 176243763	Tissue Name	Run 176243763
Secondary Th1 act	58.2	HUVEC IL-1beta	34.9
Secondary Th2 act	55.9	HUVEC IFN gamma	54.3
Secondary Tr1 act	44.1	HUVEC TNF alpha + IFN	15.8
		gamma
Secondary Th1 rest	16.3	HUVEC TNF alpha + IL4	31.4
Secondary Th2 rest	14.2	HUVEC IL-11	30.4
Secondary Tr1 rest	24.1	Lung Microvascular EC none	44.4
Primary Th1 act	26.4	Lung Microvascular EC	23.8
		TNF alpha + IL-1beta
Primary Th2 act	47.6	Microvascular Dermal EC	37.1
		none
Primary Tr1 act	36.3	Microsvasular Dermal EC	33.9
		TNF alpha + IL-1beta
Primary Th1 rest	15.3	Bronchial epithelium	17.0
		TNF alpha + IL1beta
Primary Th2 rest	11.3	Small airway epithelium none	14.3
Primary Tr1 rest	25.5	Small airway epithelium	27.4
		TNF alpha + IL-1beta
CD45RA CD4	24.5	Coronery artery SMC rest	23.3
lymphocyte act
CD45RO CD4	42.0	Coronery artery SMC	20.3
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	28.5	Astrocytes rest	15.3
Secondary CD8	36.1	Astrocytes TNF alpha + IL-	10.0
lymphocyte rest		1beta
Secondary CD8	12.7	KU-812 (Basophil) rest	50.7
lymphocyte act
CD4 lymphocyte none	14.9	KU-812 (Basophil)	56.6
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	31.9	CCD1106 (Keratinocytes)	36.1
CD95 CH11		none
LAK cells rest	55.1	CCD1106 (Keratinocytes)	27.7
		TNF alpha + IL-1beta
LAK cells IL-2	26.2	Liver cirrhosis	15.7
LAK cells IL-2 + IL-12	22.4	NCI-H292 none	25.7
LAK cells IL-2 + IFN	13.3	NCI-H292 IL-4	58.2
gamma
LAK cells IL-2 + IL-18	19.2	NCI-H292 IL-9	48.0
LAK cells	26.4	NCI-H292 IL-13	63.3
PMA/ionomycin
NK Cells IL-2 rest	26.1	NCI-H292 IFN gamma	29.7
Two Way MLR 3 day	33.4	HPAEC none	29.3
Two Way MLR 5 day	39.8	HPAEC TNF alpha + IL-1beta	51.8
Two Way MLR 7 day	21.8	Lung fibroblast none	25.7
PBMC rest	23.2	Lung fibroblast TNF alpha +	20.0
		IL-1beta
PBMC PWM	25.9	Lung fibroblast IL-4	42.9
PBMC PHA-L	30.8	Lung fibroblast IL-9	36.3
Ramos (B cell) none	0.0	Lung fibroblast IL-13	48.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	25.5
B lymphocytes PWM	16.5	Dermal fibroblast CCD1070	17.7
		rest
B lymphocytes CD40L	17.4	Dermal fibroblast CCD1070	30.1
and IL-4		TNF alpha
EOL-1 dbcAMP	65.5	Dermal fibroblast CCD1070	10.7
		IL-1beta
EOL-1 dbcAMP	66.4	Dermal fibroblast IFN gamma	20.7
PMA/ionomycin
Dendritic cells none	58.6	Dermal fibroblast IL-4	32.1
Dendritic cells LPS	46.0	Dermal fibroblasts rest	16.2
Dendritic cells anti-CD40	65.1	Neutrophils TNFa + LPS	36.1
Monocytes rest	95.9	Neutrophils rest	73.2
Monocytes LPS	100.0	Colon	9.2
Macrophages rest	65.5	Lung	62.0
Macrophages LPS	45.7	Thymus	25.9
HUVEC none	28.1	Kidney	51.1
HUVEC starved	45.7

[0776] CNS_neurodegeneration_v1.0 Summary: Ag4274 This panel confirms the expression of the CG104934-01 gene at low levels in the brain in an independent group of individuals. This gene is found to be upregulated in the temporal cortex of Alzheimer's disease patients. Blockade of this receptor may be of use in the treatment of this disease and decrease neuronal death.

[0777] General_screening_panel_v1.4 Summary: Ag4274 Highest expression of the CG104934-01 gene is detected in fetal lung (CT=23.5). Interestingly, this gene is expressed at much higher levels in fetal (CT=23.5) when compared to adult lung (CT=29.5). This observation suggests that expression of this gene can be used to distinguish fetal from adult lung. In addition, the relative overexpression of this gene in fetal lung suggests that the protein product may enhance lung growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of lung related diseases.

[0778] Significant expression of this gene is also seen in clusters of cancer cell lines derived from pancreatic, gastric, colon, renal, lung, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene may be used as a diagnostic marker for detection of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, renal, lung, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0779] Among tissues with metabolic or endocrine function, this gene is expressed at high levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0780] The CG104934-01 gene codes for a variant of potential phospholipid-transporting ATPase, a P-type ATPase with phospholipid transporting activity. In mice, a P-type ATPase (p-locus fat-associated ATPase) was mapped to locus that deletion of which results in increase in the body fat of the mice (Dhar et al, 2000, Physiol Genomics 4(1):93-100, PMID: 11074018). Therefore, based on functional homology, the CG104934-01 gene may also play a role in modulation of the body fat in human and therapeutic modulation of this protein may be useful in the treatment of obesity and diabetes.

[0781] Mutations in the FIC1 gene, a member of phospholipid-transporting ATPase, is shown to constitute the molecular defect in familial intrahepatic cholestasis I (Byler's disease) and benign recurrent intrahepatic cholestasis (Ujhazy et al., 2001, Hepatology 34:768-75, PMID: 11584374). Thus, based on homology, potential phospholipid-transporting ATPase encoded by this gene may also play a role in pathology of Byler's disease and intrahepatic cholestasis and therapeutic modulation of this protein may be useful in the treatment of these diseases.

[0782] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0783] Panel 4.1D Summary: Ag4274 Highest expression of the CG104934-01 gene is detected in monocytes (CTs=28.4). This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0784] Q. CG105463-01 and CG105463-02: Meningioma-Expressed Antigen 6/11 (MEA6) (MEA11)

[0785] Expression of gene CG105463-01 and CG105463-02 was assessed using the primer-probe set Ag4288, described in Table QA. Results of the RTQ-PCR runs are shown in Tables QB, QC and QD. Please note that CG105463-02 represents a full-length physical clone of the CG105463-01 gene, validating the prediction of the gene sequence.

TABLE QA
Probe Name Ag4288
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-agactccaaagtacacgcagaa-3′	22	834	198
Probe	TET-5′-tcacatcgagactctgactgaacgct-3′-	26	879	199
Reverse	5′-gcctgatctttgatctttagca-3′	22	905	200

[0786]

TABLE QB
CNS_neurodegeneration_v1.0
	Rel. Exp.		Rel. Exp.
	(%) Ag4288, Run		(%) Ag4288, Run
Tissue Name	224064582	Tissue Name	224064582
AD 1 Hippo	9.7	Control (Path) 3	5.4
		Temporal Ctx
AD 2 Hippo	15.1	Control (Path) 4	65.5
		Temporal Ctx
AD 3 Hippo	15.2	AD 1 Occipital Ctx	28.3
AD 4 Hippo	13.9	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	63.3	AD 3 Occipital Ctx	2.9
AD 6 Hippo	68.3	AD 4 Occipital Ctx	21.8
Control 2 Hippo	13.8	AD 5 Occipital Ctx	19.3
Control 4 Hippo	7.7	AD 6 Occipital Ctx	16.5
Control (Path) 3 Hippo	7.0	Control 1 Occipital Ctx	2.7
AD 1 Temporal Ctx	18.3	Control 2 Occipital Ctx	20.3
AD 2 Temporal Ctx	15.1	Control 3 Occipital Ctx	30.6
AD 3 Temporal Ctx	7.9	Control 4 Occipital Ctx	9.5
AD 4 Temporal Ctx	24.0	Control (Path) 1	41.5
		Occipital Ctx
AD 5 Inf Temporal Ctx	62.4	Control (Path) 2	23.5
		Occipital Ctx
AD 5 Sup Temporal	44.1	Control (Path) 3	4.6
Ctx		Occipital Ctx
AD 6 Inf Temporal Ctx	77.4	Control (Path) 4	47.6
		Occipital Ctx
AD 6 Sup Temporal	100.0	Control 1 Parietal Ctx	7.6
Ctx
Control 1 Temporal	13.7	Control 2 Parietal Ctx	46.0
Ctx
Control 2 Temporal	5.9	Control 3 Parietal Ctx	7.6
Ctx
Control 3 Temporal	11.7	Control (Path) 1	33.0
Ctx		Parietal Ctx
Control 3 Temporal	20.3	Control (Path) 2	41.5
Ctx		Parietal Ctx
Control (Path) 1	36.1	Control (Path) 3	6.5
Temporal Ctx		Parietal Ctx
Control (Path) 2	21.8	Control (Path) 4	66.4
Temporal Ctx		Parietal Ctx

[0787]

TABLE QC
General_screening_panel_v1.4
	Rel. Exp.		Rel. Exp.
	(%) Ag4288, Run		(%) Ag4288, Run
Tissue Name	222182748	Tissue Name	222182748
Adipose	11.0	Renal ca. TK-10	40.1
Melanoma*	2.6	Bladder	6.7
Hs688(A).T
Melanoma*	1.9	Gastric ca. (liver met.)	3.2
Hs688(B).T		NCI-N87
Melanoma* M14	1.5	Gastric ca. KATO III	1.6
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	5.8
Melanoma* SK-MEL-5	4.8	Colon ca. SW480	15.7
Squamous cell	1.4	Colon ca.* (SW480 met)	8.3
carcinoma SCC-4		SW620
Testis Pool	95.9	Colon ca. HT29	4.1
Prostate ca.* (bone met)	3.5	Colon ca. HCT-116	16.4
PC-3
Prostate Pool	4.5	Colon ca. CaCo-2	100.0
Placenta	0.6	Colon cancer tissue	17.6
Uterus Pool	2.7	Colon ca. SW1116	1.9
Ovarian ca. OVCAR-3	2.1	Colon ca. Colo-205	0.6
Ovarian ca. SK-OV-3	18.7	Colon ca. SW-48	5.5
Ovarian ca. OVCAR-4	0.5	Colon Pool	5.4
Ovarian ca. OVCAR-5	6.4	Small Intestine Pool	12.4
Ovarian ca. IGROV-1	30.1	Stomach Pool	5.6
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	2.6
Ovary	2.8	Fetal Heart	18.4
Breast ca. MCF-7	5.5	Heart Pool	0.8
Breast ca. MDA-MB-	1.4	Lymph Node Pool	12.8
231
Breast ca. BT 549	2.2	Fetal Skeletal Muscle	1.4
Breast ca. T47D	6.2	Skeletal Muscle Pool	9.9
Breast ca. MDA-N	1.1	Spleen Pool	4.2
Breast Pool	10.4	Thymus Pool	8.8
Trachea	7.3	CNS cancer (glio/astro)	0.6
		U87-MG
Lung	4.1	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	10.1	CNS cancer (neuro; met)	12.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	25.5	CNS cancer (astro) SNB-	6.1
		75
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	34.6
Lung ca. SHP-77	4.0	CNS cancer (glio) SF-295	0.9
Lung ca. A549	1.6	Brain (Amygdala) Pool	5.7
Lung ca. NCI-H526	0.5	Brain (cerebellum)	5.8
Lung ca. NCI-H23	5.4	Brain (fetal)	37.4
Lung ca. NCI-H460	5.0	Brain (Hippocampus) Pool	12.2
Lung ca. HOP-62	1.1	Cerebral Cortex Pool	9.4
Lung ca. NCI-H522	1.6	Brain (Substantia nigra)	6.5
		Pool
Liver	0.0	Brain (Thalamus) Pool	12.5
Fetal Liver	41.5	Brain (whole)	4.0
Liver ca. HepG2	62.0	Spinal Cord Pool	7.6
Kidney Pool	21.0	Adrenal Gland	0.0
Fetal Kidney	25.0	Pituitary gland Pool	0.6
Renal ca. 786-0	0.5	Salivary Gland	0.6
Renal ca. A498	5.0	Thyroid (female)	0.2
Renal ca. ACHN	0.5	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	12.1

[0788]

TABLE QD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4288, Run		Ag4288, Run
Tissue Name	181981927	Tissue Name	181981927
Secondary Th1 act	0.4	HUVEC IL-1beta	0.5
Secondary Th2 act	0.6	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.1
		gamma
Secondary Th1 rest	0.6	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.3	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	1.9
Primary Th1 act	0.0	Lung Microvascular EC	0.5
		TNF alpha + IL-1beta
Primary Th2 act	0.1	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	4.1
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.6
Primary Tr1 rest	0.0	Small airway epithelium	1.4
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	0.5
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	2.3
Secondary CD8	0.0	Astrocytes TNF alpha + IL-	0.8
lymphocyte rest		1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	13.6
lymphocyte act
CD4 lymphocyte none	0.3	KU-812 (Basophil)	13.5
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.5
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	1.1
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	3.8
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	0.9
gamma
LAK cells IL-2 + IL-18	0.6	NCI-H292 IL-9	1.0
LAK cells	0.0	NCI-H292 IL-13	1.2
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	1.9
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1beta	0.0
Two Way MLR 7 day	0.0	Lung fibroblast none	0.4
PBMC rest	0.7	Lung fibroblast TNF alpha +	0.9
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.4
PBMC PHA-L	0.4	Lung fibroblast IL-9	0.9
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.5
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.2
B lymphocytes PWM	1.5	Dermal fibroblast CCD1070	0.0
		rest
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070	1.5
and IL-4		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	0.7
PMA/ionomycin
Dendritic cells none	0.9	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.5
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.4
Monocytes rest	0.0	Neutrophils rest	2.6
Monocytes LPS	0.8	Colon	6.7
Macrophages rest	0.0	Lung	1.8
Macrophages LPS	0.0	Thymus	8.8
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[0789] CNS_neurodegeneration_v1.0 Summary: Ag4288 This panel confirms the expression of the CG105463-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential use of this gene in treatment of central nervous system disorders.

[0790] General_screening_panel_v1.4 Summary: Ag4288 Highest expression of the CG105463-01 gene is detected in colon cancer CaCo-2 cell line (CT=30). Significant expression is also seen in number of cancer cell lines derived from colon, renal, lung, liver, breast, ovarian, and brain cancers. Thus, expression of this gene as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, renal, lung, liver, breast, ovarian, and brain cancers.

[0791] The CG105463-01 gene codes for a homolog of meningioma-expressed antigen 6/11 (MEA6). MGEA6 is overexpressed in meningioma and glioma tumor cells. Furthermore, the immune response to MGEA6/11 is frequent in both meningioma and glioma patients (Comtesse et al., 2002, Oncogene 21(2):239-47, PMID: 11803467). Thus, based on the homology, MEA6 like protein encoded by the CG105463-01 gene may play a role in pathology of meningioma and glioma and therapeutic modulation of this gene may be beneficial in the treatment of these tumors.

[0792] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, skeletal muscle, fetal heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0793] Interestingly, this gene is expressed at much higher levels in fetal (CTs=31-32) when compared to adult liver and heart(CTs>37). This observation suggests that expression of this gene can be used to distinguish fetal heart and liver from corresponding adult tissues. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance growth or development of heart and liver in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of MEA6 like protein encoded by this gene could be useful in treatment of heart and liver related diseases.

[0794] 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, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0795] Panel 4.1D Summary: Ag4288 Highest expression of the CG105463-01 gene is detected in kidney (CT=29.3). Therefore, expression of this gene may be used to distinguish kidney from other samples used in this panel. Furthermore, therapeutic modulation of this gene product may be useful in the treatment of autoimmune and inflammatory disease that affect kidney, including lupus and glomerulonephritis.

[0796] In addition, moderate to low expression of this gene is also seen in TNFalpha+IL1beta treated bronchial epithelium, basophils, NCI-H292, resting neutrophils and normal tissues represented by colon and thymus. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis.

[0797] R. CG105491-01: Serine Protease

[0798] Expression of gene CG105491-01 was assessed using the primer-probe sets Ag4348, Ag4302 and Ag6953, described in Tables RA, RB and RC. Results of the RTQ-PCR runs are shown in Tables RD, RE and RF.

TABLE RA
Probe Name Ag4348
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-acctgctctacggacacatgt-3′	21	669	201
Probe	TET-5′-ctacatcatgcccgacatgctgtgt-3′-TAMRA	25	691	202
Reverse	5′-ctcacacacggtcttagcattc-3′	22	730	203

[0799]

TABLE RB
Probe Name Ag4302
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cctctgtaccctggagtgtatg-3′	22	839	204
Probe	TET-5′-ccagtgtttcctatttctcaaaatgga-3′-TAMRA	27	861	205
Reverse	5′-tgggcgtgatttctatgttatc-3′	22	893	206

[0800]

TABLE RC
Probe Name Ag6953
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gaaataggaaacactggcataca-3′	23	855	207
Probe	TET-5′-ctgctccaaccctctgtaccctggag-3′-TAMRA	26	829	208
Reverse	5′-ggttgcagattggaattgtg-3′	20	795	209

[0801]

TABLE RD
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4348, Run		Ag4348, Run
Tissue Name	224364195	Tissue Name	224364195
AD 1 Hippo	14.2	Control (Path) 3	6.3
		Temporal Ctx
AD 2 Hippo	30.4	Control (Path) 4	39.8
		Temporal Ctx
AD 3 Hippo	10.3	AD 1 Occipital Ctx	21.9
AD 4 Hippo	16.7	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	100.0	AD 3 Occipital Ctx	9.2
AD 6 Hippo	49.0	AD 4 Occipital Ctx	23.3
Control 2 Hippo	21.5	AD 5 Occipital Ctx	25.3
Control 4 Hippo	12.1	AD 6 Occipital Ctx	29.5
Control (Path) 3 Hippo	5.1	Control 1 Occipital	3.8
		Ctx
AD 1 Temporal Ctx	19.8	Control 2 Occipital	36.9
		Ctx
AD 2 Temporal Ctx	28.1	Control 3 Occipital	29.7
		Ctx
AD 3 Temporal Ctx	8.3	Control 4 Occipital	6.3
		Ctx
AD 4 Temporal Ctx	22.8	Control (Path) 1	65.5
		Occipital Ctx
AD 5 Inf Temporal Ctx	59.0	Control (Path) 2	18.2
		Occipital Ctx
AD 5 SupTemporal Ctx	48.3	Control (Path) 3	2.1
		Occipital Ctx
AD 6 Inf Temporal Ctx	51.1	Control (Path) 4	37.9
		Occipital Ctx
AD 6 Sup Temporal Ctx	51.8	Control 1 Parietal Ctx	8.2
Control 1 Temporal Ctx	6.7	Control 2 Parietal Ctx	53.6
Control 2 Temporal Ctx	34.2	Control 3 Parietal Ctx	26.2
Control 3 Temporal Ctx	26.8	Control (Path) 1	56.3
		Parietal Ctx
Control 4 Temporal Ctx	17.0	Control (Path) 2	33.7
		Parietal Ctx
Control (Path) 1	62.0	Control (Path) 3	6.0
Temporal Ctx		Parietal Ctx
Control (Path) 2	52.9	Control (Path) 4	49.7
Temporal Ctx		Parietal Ctx

[0802]

TABLE RE
General_screening_panel_v1.6
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag6953, Run		Ag6953, Run
Tissue Name	278388895	Tissue Name	278388895
Adipose	8.2	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	30.8
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	55.1
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	9.3	Colon ca. SW480	0.0
Squamous cell	26.6	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	100.0	Colon ca. HT29	0.0
Prostate ca.* (bone met)	9.7	Colon ca. HCT-116	0.0
PC-3
Prostate Pool	17.7	Colon ca. CaCo-2	10.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	3.1	Colon ca. SW1116	9.7
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	10.1	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	40.6
Ovarian ca. OVCAR-5	24.8	Small Intestine Pool	44.1
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	16.7
Ovary	10.3	Fetal Heart	10.2
Breast ca. MCF-7	0.0	Heart Pool	8.1
Breast ca. MDA-MB-	92.0	Lymph Node Pool	47.3
231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	35.4
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	19.5	Thymus pool	48.3
Trachea	0.0	CNS cancer (glio/astro)	10.1
		U87-MG
Lung	0.0	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	7.7	CNS cancer (neuro; met)	2.8
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	8.3	CNS cancer (astro) SNB-	0.0
		75
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	12.1
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.0	Brain (fetal)	9.5
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	7.3
		Pool
Liver	0.0	Brain (Thalamus) Pool	8.6
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.0
Kidney Pool	13.7	Adrenal Gland	0.0
Fetal Kidney	8.1	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	37.9
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0803]

TABLE RF
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4348, Run		Ag4348, Run
Tissue Name	186362432	Tissue Name	186362432
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	1.6	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	1.5	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha + IL-	0.0
lymphocyte rest		1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	1.7	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	2.3	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells	0.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	1.7
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1beta	0.0
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha +	0.0
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070	0.0
		rest
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070	0.0
and IL-4		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	0.0
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal fibroblast rest	2.0
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	3.8
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	3.5
Macrophages rest	0.0	Lung	6.8
Macrophages LPS	0.0	Thymus	7.2
HUVEC none	0.0	Kidney	100.0
HUVEC starved	1.8

[0804] CNS_neurodegeneration_v1.0 Summary: Ag4348 This panel confirms the expression of the CG105491-01 gene at low levels in the brain in an independent group of individuals. This gene is found to be slightly down-regulated in the temporal cortex of Alzheimer's disease patients. Therefore, up-regulation of this gene or its protein product, or treatment with specific agonists for this protein may be of use in reversing the dementia/memory loss associated with this disease and neuronal death.

[0805] The CG105491-01 gene codes for a serine protease. Plasmin, a member of serine protease family, is shown to increase the processing of human APP preferentially at the alpha-cleavage site, and efficiently degrades secreted amyloidogenic and non-amyloidogenic APP fragments. Brain tissue from Alzheimer's disease patients was shown to contain reduced levels of plasmin, implying that plasmin downregulation may cause amyloid plaque deposition accompanying sporadic Alzheimer's disease (Ledesma et al., 2000, EMBO Rep 1(6):530-5, PMID: 11263499). Thus, based on functional homology and also, on expression pattern, the serine protease encoded by this gene may also play a role in degradation of amyloidogenic and non-amyloidogenic APP fragments. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of Alzheimer's disease.

[0806] General_screening_panel_v1.6 Summary: Ag6953 Highest expression of this gene is detected in testis and a breast cancer MDA-MB-231 cell line (CTs=33.1). Therefore, expression of this gene may be used to distinguish these samples from other samples in this panel. In addition, low expression of this gene is detected in pancreatic, a gastric, and squamous cell cancer cell lines. Therefore, expression of this gene may be used as diagnostic marker for detection of squamous cell carcinoma, breast, pancreatic, and gastric cancers. In additon, therapeutic modulation of this gene product may be useful in the treatment of these cancers.

[0807] In addition to testis, low levels of expression of this gene is also seen in normal tissues represented by thymus, lymphnode, bladder, colon and small intestine. Therefore, therapeutic modulation of this gene may be useful in the treatment of disease associated with these tissues.

[0808] Low levels of expression of this gene is also detected in fetal skeletal muscle. Interestingly, this gene is expressed at much higher levels in fetal (CT=34.5) when compared to adult skeletal muscle (CT=40). This observation suggests that expression of this gene can be used to distinguish fetal from adult skeletal muscle. In addition, the relative overexpression of this gene in fetal skeletal muscle suggests that the protein product may enhance muscular growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of muscle related diseases. More specifically, treatment of weak or dystrophic muscle with the protein encoded by this gene could restore muscle mass or function.

[0809] Panel 4.1D Summary: Ag4348 Moderate level of expression of the CG105491-01 gene is detected only in kidney sample (CT=31.2). Therefore, expression of this gene may be used to distinguish kidney from other samples used in this panel. In addition, therapeutic modulation of this gene product may be beneficial in the treatment of autoimmune and inflammatory diseases that affect kidney, including lupus and glomerulonephritis.

[0810] S. CG105954-01: Human Ortholog of Chicken NEUROFASCIN PRECURSOR

[0811] Expression of gene CG105954-01 was assessed using the primer-probe set Ag4311, described in Table SA.

TABLE SA
Probe Name Ag4311
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aatgggatcatgattggataca-3′	22	2890	210
Probe	TET-5′-aatatgtggcctgtacgttctcccca-3′-TAMRA	26	2918	211
Reverse	5′-ttcctactttggtcccgttaac-3′	22	2944	212

[0812] T. CG105963-01: Novel Cadherin

[0813] Expression of gene CG105963-01 was assessed using the primer-probe set Ag4312, described in Table TA. Results of the RTQ-PCR runs are shown in Tables TB and TC.

TABLE TA
Probe Name Ag4312
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cagccctcatctatgactacga-3′	22	2219	213
Probe	TET-5′-acgctgagctccatcctgtccag-3′-TAMRA	23	2263	214
Reverse	5′-agtcgtagtcctggtcctcatc-3′	22	2293	215

[0814]

TABLE TB
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4312, Run		Ag4312, Run
Tissue Name	222355477	Tissue Name	222355477
Adipose	1.4	Renal ca. TK-10	7.3
Melanoma*	1.2	Bladder	0.3
Hs688(A).T
Melanoma*	1.2	Gastric ca. (liver met.)	2.1
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.7	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	1.4
Squamous cell	0.2	Colon ca.* (SW480 met)	0.5
carcinoma SCC-4		SW620
Testis Pool	0.3	Colon ca. HT29	0.0
Prostate ca.* (bone met)	13.8	Colon ca. HCT-116	8.1
PC-3
Prostate Pool	0.6	Colon ca. CaCo-2	0.0
Placenta	0.3	Colon cancer tissue	0.5
Uterus Pool	0.0	Colon ca. SW1116	1.3
Ovarian ca. OVCAR-3	0.5	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.4	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	1.3	Colon Pool	0.4
Ovarian ca. OVCAR-5	9.0	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	3.4	Stomach Pool	0.0
Ovarian ca. OVCAR-8	7.7	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	1.0	Heart Pool	0.1
Breast ca. MDA-MB-	1.1	Lymph Node Pool	0.3
231
Breast ca. BT 549	0.6	Fetal Skeletal Muscle	38.7
Breast ca. T47D	17.4	Skeletal Muscle Pool	34.4
Breast ca. MDA-N	0.0	Spleen Pool	0.3
Breast Pool	0.0	Thymus pool	0.3
Trachea	0.2	CNS cancer (glio/astro)	9.6
		U87-MG
Lung	0.1	CNS cancer (glio/astro) U-	0.1
		118-MG
Fetal Lung	1.3	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	21.2	CNS cancer (astro) SF-539	4.3
Lung ca. LX-1	1.7	CNS cancer (astro) SNB-	14.4
		75
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	3.8
Lung ca. SHP-77	1.2	CNS cancer (glio) SF-295	6.7
Lung ca. A549	0.1	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	100.0
Lung ca. NCI-H23	0.2	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	8.8	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.7	Brain (Substantia nigra)	0.1
		Pool
Liver	0.5	Brain (Thalamus) Pool	0.1
Fetal Liver	0.5	Brain (whole)	9.7
Liver ca. HepG2	18.9	Spinal Cord Pool	0.0
Kidney Pool	0.2	Adrenal Gland	0.6
Fetal Kidney	1.8	Pituitary gland Pool	0.0
Renal ca. 786-0	0.2	Salivary Gland	0.1
Renal ca. A498	0.6	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.2

[0815]

TABLE TC
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4312, Run		Ag4312, Run
Tissue Name	182243751	Tissue Name	182243751
Secondary Th1 act	0.0	HUVEC IL-1beta	0.3
Secondary Th2 act	0.0	HUVEC IFN gamma	0.3
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	1.5
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	4.6
Primary Th1 act	0.0	Lung Microvascular EC	0.4
		TNF alpha + IL-1beta
Primary Th2 act	0.1	Microvascular Dermal EC	0.2
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.5
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4	0.1	Coronery artery SMC rest	1.2
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	2.1
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha + IL-	0.0
lymphocyte rest		1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.1	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	0.3
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells	0.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1beta	2.4
Two Way MLR 7 day	0.0	Lung fibroblast none	0.5
PBMC rest	0.0	Lung fibroblast TNF alpha +	4.0
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.7
Ramos (B cell) none	0.0	Lung fibroblast IL-13	1.3
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070	1.1
		rest
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070	0.0
and IL-4		TNF alpha
EOL-1 dbcAMP	0.1	Dermal fibroblast CCD1070	0.1
		IL-1beta
EOL-1 dbcAMP	0.6	Dermal fibroblast IFN gamma	0.4
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.1
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.2
Monocytes rest	0.0	Neutrophils rest	0.7
Monocytes LPS	0.0	Colon	0.1
Macrophages rest	0.0	Lung	2.4
Macrophages LPS	0.0	Thymus	13.9
HUVEC none	0.1	Kidney	100.0
HUVEC starved	0.2

[0816] General_screening_panel_v1.4 Summary: Ag4312 Highest expression of the CG105963-01 gene is detected in brain (cerebellum) (Ct=28.8). In addition, moderate expression of this gene is also seen in whole brain sample. The CG105963-01 gene codes for a variant of cadherin-15 (M-cadherin). Cadherins are calcium-dependent, transmembrane intercellular adhesion proteins with morphoregulatory functions in the development and maintenance of tissues. Cadherins can act as axon guidance and cell adhesion proteins, specifically during development and in the response to injury (Ranscht B., 2000, Int. J. Dev. Neurosci. 18: 643-651, PMID: 10978842). In addition, M-cadherin is involved in muscle cell, Schwann cell, and motoneuron interactions and also in differentiation during neuromuscular development (Padilla et al., 1998, Mol Cell Neurosci 11(4):217-33, PMID: 9675053). Therefore, therapeutic modulation of this protein may be useful in inducing a compensatory synaptogenic response to neuronal death in Alzheimer's disease, Parkinson's disease, Huntington's disease, spinocerebellar ataxia, progressive supranuclear palsy, ALS, head trauma, stroke, or any other disease/condition associated with neuronal loss.

[0817] In addition, low to moderate levels of expression of this gene is also seen in number of cancer cell lines including CNS cancer, colon, renal, liver, lung, breast, ovarian and prostate cancer cell lines. Therefore, therapeutic modulation of this gene product may be useful in the treatment of these cancers.

[0818] Moderate expression of this gene is also seen in skeletal muscle. M-cadherin is shown to be important for skeletal muscle development, in particular the fusion of myoblasts into myotubes (Kaufmann et al., 1999, J Cell Sci 112:55-68, PMID: 9841904). Therefore, therapeutic modulation of this gene may be beneficial in the treatment of muscle related disease

[0819] Panel 4.1D Summary: Ag4312 Highest expression of the CG105963-01 gene is detected in kidney (CT=28.3). Therefore, expression of this gene may be used to distinguish kidney sample from other samples used in this panel. In addition, moderate to low expression of this gene is also seen in thymus, lung, TNF alpha+IL-1 beta treated lung fibroblasts and endothelial cells represent by HPAEC and HUVEC, coronery artery, and lung microvascular EC. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of autoimmune and inflammatory diseases affecting kidney and lung including lupus erythematosus, asthma, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, osteoarthritis, and psoriasis.

[0820] U. CG105973-01 and CG105973-02: Integrin Alpha-8

[0821] Expression of gene CG105973-01 and CG105973-02 was assessed using the primer-probe sets Ag4305 and Ag4313, described in Tables UA and UB. Results of the RTQ-PCR runs are shown in Tables UC, UD, UE, UF and UG. Please note that CG105973-02 represents a full-length physical clone of the CG105973-01 gene, validating the prediction of the gene sequence.

TABLE UA
Probe Name Ag4305
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-agttccacgtcttgagaaaaca-3′	22	2589	216
Probe	TET-5′-tgagcattaacttcgatctccaaatca-3′-TAMRA	27	2615	217
Reverse	5′-gctgtctggattgtccttgtt-3′	21	2650	218

[0822]

TABLE UB
Probe Name Ag4313
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-agttccacgtcttgagaaaaca-3′	22	2589	219
Probe	TET-5′-tgagcattaacttcgatctccaaatca-3′-TAMRA	27	2615	220
Reverse	5′-gctgtctggattgtccttgtt-3′	21	2650	221

[0823]

TABLE UC
AI_comprehensive panel_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4305, Run		Ag4305, Run
Tissue Name	244570379	Tissue Name	244570379
110967 COPD-F	17.0	112427 Match Control	37.1
		Psoriasis-F
110980 COPD-F	59.5	112418 Psoriasis-M	14.5
110968 COPD-M	15.7	112723 Match Control	0.0
		Psoriasis-M
110977 COPD-M	76.8	112419 Psoriasis-M	33.0
110989 Emphysema-F	22.8	112424 Match Control	15.6
		Psoriasis-M
110992 Emphysema-F	4.6	112420 Psoriasis-M	27.2
110993 Emphysema-F	21.6	112425 Match Control	28.1
		Psoriasis-M
110994 Emphysema-F	14.3	104689 (MF) OA Bone-	17.2
		Backus
110995 Emphysema-F	10.2	104690 (MF) Adj “Normal”	18.7
		Bone-Backus
110996 Emphysema-F	0.0	104691 (MF) OA	10.4
		Synovium-Backus
110997 Asthma-M	13.9	104692 (BA) OA Cartilage-	0.0
		Backus
111001 Asthma-F	17.1	104694 (BA) OA Bone-	6.3
		Backus
111002 Asthma-F	14.8	104695 (BA) Adj “Normal”	16.8
		Bone-Backus
111003 Atopic Asthma-F	23.0	104696 (BA) OA	6.0
		Synovium-Backus
111004 Atopic Asthma-F	17.1	104700 (SS) OA Bone-	11.8
		Backus
111005 Atopic Asthma-F	12.8	104701 (SS) Adj “Normal”	10.2
		Bone-Backus
111006 Atopic Asthma-F	5.1	104702 (SS) OA	23.3
		Synovium-Backus
111417 Allergy-M	13.6	117093 OA Cartilage Rep7	18.8
112347 Allergy-M	7.1	112672 OA Bone5	36.9
112349 Normal Lung-F	5.7	112673 OA Synovium5	17.6
112357 Normal Lung-F	12.9	112674 OA Synovial Fluid	17.0
		cells5
112354 Normal Lung-M	59.9	117100 OA Cartilage	5.0
		Rep14
112374 Crohns-F	8.0	112756 OA Bone9	0.2
112389 Match Control	24.3	112757 OA Synovium9	3.3
Crohns-F
112375 Crohns-F	14.3	112758 OA Synovial Fluid	11.0
		Cells9
112732 Match Control	6.2	117125 RA Cartilage Rep2	19.1
Crohns-F
112725 Crohns-M	11.3	113492 Bone2 RA	40.9
112387 Match Control	5.9	113493 Synovium2 RA	21.6
Crohns-M
112378 Crohns-M	7.5	113494 Syn Fluid Cells RA	34.4
112390 Match Control	32.3	113499 Cartilage4 RA	21.3
Crohns-M
112726 Crohns-M	100.0	113500 Bone4 RA	26.8
112731 Match Control	47.0	113501 Synovium4 RA	24.3
Crohns-M
112380 Ulcer Col-F	17.1	113502 Syn Fluid Cells4	13.5
		RA
112734 Match Control	14.3	113495 Cartilage3 RA	28.3
Ulcer Col-F
112384 Ulcer Col-F	17.6	113496 Bone3 RA	33.0
112737 Match Control	35.1	113497 Synovium3 RA	15.7
Ulcer Col-F
112386 Ulcer Col-F	3.0	113498 Syn Fluid Cells3	39.2
		RA
112738 Match Control	6.7	117106 Normal Cartilage	4.3
Ulcer Col-F		Rep20
112381 Ulcer Col-M	33.2	113663 Bone3 Normal	12.7
112735 Match Control	40.9	113664 Synovium3 Normal	1.5
Ulcer Col-M
112382 Ulcer Col-M	37.9	113665 Syn Fluid Cells3	7.5
		Normal
112394 Match Control	0.2	117107 Normal Cartilage	10.0
Ulcer Col-M		Rep22
112383 Ulcer Col-M	3.5	113667 Bone4 Normal	13.5
112736 Match Control	19.2	113668 Synovium4 Normal	16.3
Ulcer Col-M
112423 Psoriasis-F	39.2	113669 Syn Fluid Cells4	20.2
		Normal

[0824]

TABLE UD
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag4305, Run	Ag4313, Run		Ag4305, Run	Ag4313, Run
Tissue Name	224074285	224064613	Tissue Name	224074285	224064613
AD 1 Hippo	24.0	29.1	Control (Path)	17.0	28.5
			3 Temporal
			Ctx
AD 2 Hippo	36.9	39.0	Control (Path)	37.1	39.0
			4 Temporal
			Ctx
AD 3 Hippo	25.9	34.2	AD 1 Occipital	20.4	18.4
			Ctx
AD 4 Hippo	9.2	9.4	AD 2 Occipital	0.0	0.0
			Ctx (Missing)
AD 5 Hippo	55.9	76.8	AD 3 Occipital	15.2	9.9
			Ctx
AD 6 Hippo	100.0	100.0	AD 4 Occipital	20.9	25.9
			Ctx
Control 2	37.6	32.3	AD 5 Occipital	50.7	22.7
Hippo			Ctx
Control 4	27.9	25.7	AD 6 Occipital	32.1	59.5
Hippo			Ctx
Control (Path)	44.4	54.7	Control 1	9.6	13.2
3 Hippo			Occipital Ctx
AD 1	30.8	25.2	Control 2	32.3	40.9
Temporal Ctx			Occipital Ctx
AD 2	43.5	52.1	Control 3	25.0	26.2
Temporal Ctx			Occipital Ctx
AD 3	15.3	20.4	Control 4	14.9	27.5
Temporal Ctx			Occiptial Ctx
AD 4	28.3	37.4	Control (Path)	47.3	64.2
Temporal Ctx			1 Occipital Ctx
AD 5 Inf	66.0	70.7	Control (Path)	12.7	18.0
Temporal Ctx			2 Occipital Ctx
AD 5 Sup	73.2	69.7	Control (Path)	9.0	12.8
Temporal Ctx			3 Occipital Ctx
AD 6 Inf	40.3	43.5	Control (Path)	25.2	37.1
Temporal Ctx			4 Occipital Ctx
AD 6 Sup	62.9	62.4	Control 1	14.3	13.1
Temporal Ctx			Parietal Ctx
Control 1	13.4	20.0	Control 2	60.7	51.8
Temporal Ctx			Parietal Ctx
Control 2	28.5	27.4	Control 3	40.9	33.7
Temporal Ctx			Parietal Ctx
Control 3	25.3	22.4	Control (Path)	42.0	62.9
Temporal Ctx			1 Parietal Ctx
Control 3	24.7	20.2	Control (Path)	42.6	38.2
Temporal Ctx			2 Parietal Ctx
Control (Path)	54.7	66.0	Control (Path)	21.6	19.6
1 Temporal			3 Parietal Ctx
Ctx
Control (Path)	36.6	33.9	Control (Path)	59.5	77.9
2 Temporal			4 Parietal Ctx
Ctx

[0825]

TABLE UE
General_screening_panel_v1.4
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag4305, Run	Ag4313, Run		Ag4305, Run	Ag4313, Run
Tissue Name	222261511	222360603	Tissue Name	222261511	222360603
Adipose	8.7	9.5	Renal ca. TK-10	0.0	0.0
Melanoma*	19.8	20.0	Bladder	2.7	3.0
Hs688(A).T
Melanoma*	18.0	15.0	Gastric ca. (liver	0.0	0.0
Hs688(B).T			met.) NCI-N87
Melanoma*	0.0	0.0	Gastric ca. KATO	0.0	0.0
M14			III
Melanoma*	0.0	0.0	Colon ca. SW-948	0.0	0.0
LOXIMVI
Melanoma* SK-	0.0	0.0	Colon ca. SW480	0.0	0.0
MEL-5
Squamous cell	0.0	0.0	Colon ca.* (SW480	0.0	0.0
carcinoma SCC-4			met) SW620
Testis Pool	10.8	8.9	Colon ca. HT29	0.0	0.0
Prostate ca.*	0.0	0.0	Colon ca. HCT-116	0.0	0.0
(bone met) PC-3
Prostate Pool	27.9	24.0	Colon ca. CaCo-2	0.0	0.0
Placenta	0.0	0.0	Colon cancer tissue	2.2	1.7
Uterus Pool	13.2	10.4	Colon ca. SW1116	0.0	0.0
Ovarian ca.	0.0	0.0	Colon ca. Colo-205	0.0	0.0
OVCAR-3
Ovarian ca. SK-	0.0	0.0	Colon ca. SW-48	0.0	0.0
OV-3
Ovarian ca.	0.0	0.0	Colon Pool	18.3	19.8
OVCAR-4
Ovarian ca.	0.0	0.0	Small Intestine	13.9	11.7
OVCAR-5			Pool
Ovarian ca.	0.0	0.0	Stomach Pool	10.0	10.6
IGROV-1
Ovarian ca.	0.0	0.0	Bone Marrow Pool	20.9	20.2
OVACAR-8
Ovary	1.9	1.3	Fetal Heart	3.7	2.7
Breast ca. MCF-7	0.0	0.0	Heart Pool	17.0	15.4
Breast ca.	0.0	0.0	Lymph Node Pool	29.5	24.1
MDA-MB-231
Breast ca. BT	0.0	0.0	Fetal Skeletal	5.6	4.2
549			Muscle
Breast ca. T47D	0.0	0.0	Skeletal Muscle	5.7	4.7
			Pool
Breast ca.	0.0	0.0	Spleen Pool	37.4	31.2
MDA-N
Breast Pool	20.9	17.6	Thymus Pool	8.2	7.6
Trachea	14.1	12.7	CNS cancer	0.1	0.0
			(glio/astro) U87-
			MG
Lung	21.5	18.6	CNS cancer	28.9	25.5
			(glio/astro) U-118-
			MG
Fetal Lung	100.0	100.0	CNS cancer	83.5	69.7
			(neuro;met) SK-N-
			AS
Lung ca. NCI-	0.0	0.0	CNS cancer (astro)	0.3	0.0
N417			SF-539
Lung ca. LX-1	0.0	0.0	CNS cancer (astro)	0.3	0.0
			SNB-75
Lung ca. NCI-	0.0	0.0	CNS cancer (glio)	0.0	0.0
H146			SNB-19
Lung ca. SHP-	0.0	0.0	CNS cancer (glio)	40.6	35.1
77			SF-295
Lung ca. A549	0.0	0.0	Brain (Amygdala)	2.2	2.3
			Pool
Lung ca. NCI-	0.0	0.0	Brain (cerebellum)	5.2	3.7
H526
Lung ca. NCI-	0.5	0.1	Brain (fetal)	3.2	3.9
H23
Lung ca. NCI-	0.0	0.0	Brain	6.4	5.0
H460			(Hippocampus)
			Pool
Lung ca. HOP-	0.0	0.0	Cerebral Cortex	3.6	3.2
62			Pool
Lung ca. NCI-	0.0	0.0	Brain (Substantia	2.2	2.4
H522			nigra) Pool
Liver	0.1	0.0	Brain (Thalamus)	5.7	5.9
			Pool
Fetal Liver	3.7	3.0	Brain (whole)	2.5	2.6
Liver ca.	0.0	0.0	Spinal Cord Pool	3.6	2.3
HepG2
Kidney Pool	52.9	42.0	Adrenal Gland	17.0	21.2
Fetal Kidney	45.1	40.3	Pitutitary gland	3.7	2.7
			Pool
Renal ca. 786-0	0.0	0.0	Salivary Gland	1.3	0.2
Renal ca. A498	0.0	0.0	Thyroid (female)	2.9	2.7
Renal ca.	0.0	0.0	Pancreatic ca.	0.0	0.0
ACHN			CAPAN2
Renal ca. UO-	0.0	0.0	Pancreas Pool	8.4	8.9
31

[0826]

TABLE UF
Panel 4.1D
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag4305, Run	Ag4313, Run		Ag4305, Run	Ag4313, Run
Tissue Name	182086760	182244195	Tissue Name	182086760	182244195
Secondary Th1 act	0.0	0.0	HUVEC IL-1beta	0.6	0.0
Secondary Th2 act	0.0	0.0	HUVEC IFN gamma	0.0	0.0
Secondary Tr1 act	0.0	0.0	HUVEC TNF alpha +	0.0	0.0
			IFN gamma
Secondary Th1 rest	0.0	0.0	HUVEC TNF alpha +	0.0	0.0
			IL4
Secondary Th2 rest	0.0	0.0	HUVEC IL-11	0.0	0.0
Secondary Tr1 rest	0.0	0.0	Lung Microvascular	0.3	0.0
			EC none
Primary Th1 act	0.0	0.0	Lung Microvascular	3.9	0.0
			EC TNF alpha + IL-
			1beta
Primary Th2 act	0.0	0.0	Microvascular	0.0	0.0
			Dermal EC none
Primary Tr1 act	0.0	0.0	Microsvasular	0.0	1.0
			Dermal EC
			TNF alpha + IL-1beta
Primary Th1 rest	0.0	0.0	Bronchial epithelium	0.0	0.0
			TNF alpha + IL1beta
Primary Th2 rest	0.0	0.0	Small airway	0.0	0.0
			epithelium none
Primary Tr1 rest	0.0	0.0	Small airway	0.0	0.0
			epithelium TNF alpha +
			IL-1beta
CD45RA CD4	3.8	8.7	Coronery artery	0.0	0.0
lymphocyte act			SMS rest
CD45RO CD4	0.0	0.0	Coronery artery	0.0	0.0
lymphocyte act			SMC TNF alpha +
			IL-1beta
CD8 lymphocyte act	0.0	0.0	Astrocytes rest	0.0	0.0
Secondary CD8	0.0	0.0	Astrocytes TNF alpha +	0.0	0.0
lymphocyte rest			IL-1beta
Secondary CD8	0.0	0.0	KU-812 (Basophil)	0.0	0.0
lymphocyte act			rest
CD4 lymphocyte	0.0	0.0	KU-812 (Basophil)	0.0	0.0
none			PMA/ionomycin
2ry	0.0	0.0	CCD1106	0.0	0.0
Th1/Th2/Tr1_anti-			(Keratinocytes) none
CD95 CH11
LAK cells rest	0.0	0.0	CCD1106	0.0	0.0
			(Keratinocytes)
			TNF alpha + IL-1beta
LAK cells IL-2	0.0	0.0	Liver cirrhosis	13.9	31.0
LAK cells IL-2 + IL-	0.0	0.0	NCI-H292 none	0.0	0.0
12
LAK cells IL-2 + IFN	0.0	0.0	NCI-H292 IL-4	0.0	0.0
gamma
LAK cells IL-2 + IL-	0.0	0.0	NCI-H292 IL-9	0.0	0.0
18
LAK cells	0.0	0.0	NCI-H292 IL-13	0.4	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	0.0	NCI-H292 IFN	0.0	0.0
			gamma
Two Way MLR 3	0.0	0.0	HPAEC none	0.0	0.0
day
Two Way MLR 5	0.0	0.0	HPAEC TNF alpha +	0.0	1.2
day			IL-1beta
Two Way MLR 7	0.0	0.0	Lung fibroblast none	3.5	0.0
day
PBMC rest	0.0	0.0	Lung fibroblast TNF	0.6	1.9
			alpha + IL-1beta
PBMC PWM	0.0	0.0	Lung fibroblast IL-4	0.0	1.4
PBMC PHA-L	0.0	0.0	Lung fibroblast IL-9	1.8	2.1
Ramos (B cell) none	0.0	0.0	Lung fibroblast IL-	2.4	0.0
			13
Ramos (B cell)	0.0	0.0	Lung fibroblast IFN	0.0	4.1
ionomycin			gamma
B lymphocytes	1.9	0.0	Dermal fibroblast	3.9	9.7
PWM			CCD1070 rest
B lymphocytes	0.0	0.0	Dermal fibroblast	6.0	6.8
CD40L and IL-4			CCD1070 TNF alpha
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	16.0	10.5
			CCD1070 IL-1beta
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	26.2	57.4
PMA/ionomycin			IFN gamma
Dendritic cells none	0.0	0.0	Dermal fibroblast IL-4	30.4	51.8
Dendritic cells LPS	0.0	0.0	Dermal Fibroblasts	45.1	66.0
			rest
Dendritic cells anti-	0.0	0.0	Neutrophils	0.0	4.3
CD40			TNFa + LPS
Monocytes rest	0.0	0.0	Neutrophils rest	1.2	5.0
Monocytes LPS	0.0	0.0	Colon	14.5	23.5
Macrophages rest	0.0	0.0	Lung	100.0	100.0
Macrophages LPS	0.0	0.0	Thymus	16.4	22.8
HUVEC none	0.4	0.0	Kidney	48.0	71.2
HUVEC starved	0.0	0.0

[0827]

TABLE UG
Panel 5 Islet
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4305, Run		Ag4305, Run
Tissue Name	248029384	Tissue Name	248029384
97457_Patient-	16.4	94709_Donor 2 AM - A_adipose	30.1
02go_adipose
97476_Patient-	52.5	94710_Donor 2 AM - B_adipose	17.8
07sk_skeletal muscle
97477_Patient-07ut_uterus	67.8	94711_Donor 2 AM - C_adipose	6.3
97478_Patient-	0.5	94712_Donor 2 AD - A_adipose	55.1
07pl_placenta
99167_Bayer Patient 1	13.0	94713_Donor 2 AD - B_adipose	88.3
97482_Patient-08ut_uterus	81.2	94714_Donor 2 AD - C_adipose	81.8
97483_Patient-	0.0	94742_Donor 3 U - A_Mesenchymal	11.3
08pl_placenta		Stem Cells
97486_Patient-	15.4	94743_Donor 3 U - B_Mesenchymal	12.5
09sk_skeletal muscle		Stem Cells
97487_Patient-09ut_uterus	100.0	94730_Donor 3 AM - A_adipose	47.0
97488_Patient-	0.0	94731_Donor 3 AM - B_adipose	12.5
09pl_placenta
97492_Patient-10ut_uterus	63.7	94732_Donor 3 AM - C_adipose	20.6
97493_Patient-	4.6	94733_Donor 3 AD - A_adipose	76.8
10pl_placenta
97495_Patient-	26.4	94734_Donor 3 AD - B_adipose	27.2
11go_adipose
97496_Patient-	33.2	94735_Donor 3 AD - C_adipose	39.0
11sk_skeletal muscle
97497_Patient-11ut_uterus	62.9	77138_Liver_HepG2untreated	0.0
97498_Patient-	0.0	73556_Heart_Cardiac stromal cells	0.0
11pl_placenta		(primary)
97500_Patient-	26.6	81735_Small Intestine	50.3
12go_adipose
97501_Patient-	28.7	72409_Kidney_Proximal Convoluted	0.0
12sk_skeletal muscle		Tubule
97502_Patient-12ut_uterus	73.7	82685_Small intestine_Duodenum	41.5
97503_Patient-	0.0	90650_Adrenal_Adrenocortical	12.9
12pl_placenta		adenoma
94721_Donor 2 U —	1.7	72410_Kidney_HRCE	0.0
A_Mesenchymal Stem
Cells
94722_Donor 2 U —	0.0	72411_Kidney_HRE	2.4
B_Mesenchymal Stem
Cells
94723_Donor 2 U —	2.1	73139_Uterus_Uterine smooth	11.5
C_Mesenchymal Stem		muscle cells
Cells

[0828] AI_comprehensive panel_v1.0 Summary: Ag4305 Highest expression of the CG105973-01 gene is detected in Crohn's sample (CT=28.8). Low to moderate levels of expression of this gene are detected in samples derived from osteoarthritic (OA) bone and adjacent bone as well as OA cartilage, OA synovium and OA synovial fluid samples, and in cartilage, bone, synovium and synovial fluid samples from rheumatoid arthritis patients. Low level expression is also detected in samples derived from normal lung samples, COPD lung, emphysema, atopic asthma, asthma, allergy, Crohn's disease (normal matched control and diseased), ulcerative colitis(normal matched control and diseased), and psoriasis (normal matched control and diseased). Therefore, therapeutic modulation of this gene product may ameliorate symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis

[0829] CNS_neurodegeneration_v1.0 Summary: Ag4305/Ag4313 Two experiments with same primer and probe set are in excellent agreements, with highest expression of the CG105973-01 gene in a hippocampus sample from Alzheimer's patient (CTs=31). This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential use of this gene in treatment of central nervous system disorders.

[0830] General_screening_panel_v1.4 Summary: Ag4305/Ag4313 Two experiments with same primer and probe set are in excellent agreements, with highest expression of the CG105973-01 gene in fetal lung (Cts=27.7). Although, this gene appears to be expressed mainly in the normal tissues used in this panel, significant expression of this gene is also seen in two melanoma and three CNS cancer cell lines and colon cancer tissue. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of these cancers.

[0831] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0832] 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, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression and therapeutic modulation of this gene product may be useful in the treatment of these neurological disorders.

[0833] Panel 4.1D Summary: Ag4305/Ag4313 Two experiments with same primer and probe set are in excellent agreements, with highest expression of the CG105973-01 gene in lung (CTs=31-32). In addition, moderate to low levels of expression of this gene is also seen in liver cirrhosis, dermal fibroblasts and normal tissues represented by colon, thymus, and kidney. Therefore, therapeutic modulation of this gene may be useful in the treatment of autoimmune and inflammatory diseases that affect lung,colon and kidney, such as lupus erythematosus, asthma, emphysema, Crohn's disease, ulcerative colitis, and psoriasis.

[0834] The CG105973-01 gene codes for a variant of integrin alpha-8. In the kidney, the alpha8 integrin chain is expressed in glomerular mesangial cells and it plays a role in early nephrogenesis. In mice the alpha8 integrin chain maintains the integrity of the glomerular capillary tuft during mechanical stress, eg, in hypertension (Hartner et al., 2002, Am J Pathol 160 :861-7, PMID: 11891185). Therefore, therapeutic modulation of this gene may be useful in the treatment of glomerular mesangial cell related diseases such as glomerulonephritis.

[0835] Panel 5 Islet Summary: Ag4305 Highest expression of the CG105973-01 gene is detected in uterus (CT=31). This gene is expressed at moderate to low levels in tissues with metabolic or endocrine function including adipose, uterus, small intestine and kidney. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0836] In addition, this gene is expressed at low levels (CT=34) in human islets. Integrins are found at the insulin-secreting beta cell surface in situ. Insulin secretagogues upregulate the beta cell-surface expression of some classes of integrins (Bosco et al., 2000, Diabetes 49(2):233-43, PMID: 10868940). Thus, therapeutic modulation of this gene product may increase beta cell insulin secretion and may be useful in the treatment of Type 2 diabetes.

[0837] V. CG106915-01 and CG106924-01: Novel Nogo Receptor Isoform-2

[0838] Expression of gene CG106924-01 was assessed using the primer-probe sets Ag4329, Ag4330 and Ag6865, described in Tables VA, VB and VC. Results of the RTQ-PCR runs are shown in Tables VD, VE and VF. Please note that probe Ag4330 is specific for the variant CG106924-01.

TABLE VA
Probe Name Ag4329
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cctatgaccactgagggtttt-3′	20	106	222
Probe	TET-5′-tcatcaccgatggatatctctcctct-3′-TAMRA	26	128	223
Reverse	5′-ggagagcagggcaagattaa-3′	20	182	224

[0839]

TABLE VB
Probe Name Ag4330
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gcttgatgaaagcaagacaga-3′	21	3270	225
Probe	TET-5′-ctcagatctcacaaatgacctttaaaagg-3′-TAMRA	28	3305	226
Reverse	5′-gctgcctttcttttgtgatg-3′	20	3333	227

[0840]

TABLE VC
Probe Name Ag6865
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gctgcacttgtgatctccat-3′	20	662	228
Probe	TET-5′-acattaagtcttctgcTCACACGCTC-3′-TAMRA	26	707	229
Reverse	5′-atttaggtccttggcattcct-3′	21	733	230

[0841]

TABLE VD
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag4329, Run	Ag4330, Run		Ag4329, Run	Ag4330, Run
Tissue Name	224344077	224344731	Tissue Name	224344077	224344731
AD 1 Hippo	21.9	16.5	Control (Path)	3.9	0.0
			3 Temporal
			Ctx
AD 2 Hippo	36.9	8.2	Control (Path)	40.3	35.6
			4 Temporal
			Ctx
AD 3 Hippo	13.6	16.7	AD 1	28.1	15.8
			Occipital Ctx
AD 4 Hippo	11.7	2.1	AD 2	0.0	0.0
			Occipital Ctx
			(Missing)
AD 5 hippo	96.6	40.9	AD 3	6.2	4.0
			Occipital Ctx
AD 6 Hippo	100.0	17.6	AD 4	25.0	19.1
			Occipital Ctx
Control 2 Hippo	11.4	29.9	AD 5	60.7	43.2
			Occipital Ctx
Control 4 Hippo	18.0	13.5	AD 6	39.2	19.2
			Occipital Ctx
Control (Path) 3	6.0	5.8	Control 1	0.0	1.1
Hippo			Occipital Ctx
AD 1 Temporal	7.2	5.4	Control 2	72.2	51.4
Ctx			Occipital Ctx
AD 2 Temporal	18.8	47.3	Control 3	33.4	16.0
Ctx			Occipital Ctx
AD 3 Temporal	0.0	6.0	Control 4	9.7	1.3
Ctx			Occipital Ctx
AD 4 Temporal	19.8	16.6	Control (Path)	85.9	81.8
Ctx			1 Occipital
			Ctx
AD 5 Inf	53.6	100.0	Control (Path)	17.3	19.3
Temporal Ctx			2 Occipital
			Ctx
AD 5	23.8	33.7	Control (Path)	0.0	1.9
Sup Temporal Ctx			3 Occipital
			Ctx
AD 6 Inf	72.2	27.2	Control (Path)	23.0	23.5
Temporal Ctx			4 Occipital
			Ctx
AD 6 Sup	54.7	25.9	Control 1	4.9	10.6
Temporal Ctx			Parietal Ctx
Control 1	6.8	7.0	Control 2	46.0	26.1
Temporal Ctx			Parietal Ctx
Control 2	49.0	44.4	Control 3	39.2	11.0
Temporal Ctx			Parietal Ctx
Control 3	28.7	3.3	Control (Path)	95.9	54.3
Temporal Ctx			1 Parietal Ctx
Control 4	9.5	1.6	Control (Path)	53.2	42.0
Temporal Ctx			2 Parietal Ctx
Control (Path) 1	40.9	50.3	Control (Path)	8.1	1.9
Temporal Ctx			3 Parietal Ctx
Control (Path) 2	48.0	23.8	Control (Path)	64.6	37.9
Temporal Ctx			4 Parietal Ctx

[0842]

TABLE VE
General_screening_panel_v1.4
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag4329, Run	Ag4330, Run		Ag4329, Run	Ag4330, Run
Tissue Name	222550606	222550615	Tissue Name	222550606	222550615
Adipose	0.0	0.0	Renal ca. TK-10	0.0	0.0
Melanoma*	0.0	0.0	Bladder	0.7	2.7
Hs688(A).T
Melanoma*	0.0	0.0	Gastric ca. (liver	1.9	0.0
Hs688(B).T			met.) NCI-N87
Melanoma*	0.0	0.0	Gastric ca. KATO	0.0	0.0
M14			III
Melanoma*	0.0	0.0	Colon ca. SW-948	0.0	0.0
LOXIMVI
Melanoma* SK-	0.0	0.0	Colon ca. SW480	0.0	0.0
MEL-5
Squamous cell	0.0	0.0	Colon ca.* (SW480	0.0	0.0
carcinoma SCC-4			met) SW620
Testis Pool	3.2	5.1	Colon ca. HT29	0.0	3.0
Prostate ca.*	0.0	0.0	Colon ca. HCT-116	0.0	0.0
(bone met) PC-3
Prostate Pool	0.4	1.7	Colon ca. CaCo-2	0.0	0.0
Placenta	0.0	0.0	Colon cancer tissue	0.0	0.0
Uterus Pool	0.0	1.0	Colon ca. SW1116	0.0	0.0
Ovarian ca.	0.0	0.6	Colon ca. Colo-205	0.0	0.0
OVCAR-3
Ovarian ca. SK-	0.0	1.0	Colon ca. SW-48	0.0	0.0
OV-3
Ovarian ca.	0.0	0.0	Colon Pool	0.8	1.4
OVCAR-4
Ovarian ca.	0.0	0.0	Small Intestine	1.2	2.6
OVCAR-5			Pool
Ovarian ca.	0.0	0.9	Stomach Pool	0.4	2.5
IGROV-1
Ovarian ca.	0.0	0.0	Bone Marrow Pool	0.3	0.8
OVCAR-8
Ovary	0.9	0 6	Fetal Heart	100.0	100.0
Breast ca. MCF-7	0.0	0.0	Heart Pool	10.2	16.5
Breast ca.	0.0	0.0	Lymph Node Pool	5.0	2.3
MDA-MB-231
Breast ca. BT	0.4	0.0	Fetal Skeletal	0.0	0.0
549			Muscle
Breast ca. T47D	0.0	1.6	Skeletal Muscle	1.7	1.1
			Pool
Breast ca.	0.0	0.0	Spleen Pool	1.2	1.0
MDA-N
Breast Pool	1.8	3.1	Thymus Pool	1.2	4.3
Trachea	0 0	0.0	CNS cancer	0.0	0.0
			(glio/astro) U87-
			MG
Lung	1.0	1.6	CNS cancer	0.0	0.0
			(glio/astro) U-118-
			MG
Fetal Lung	0.4	0.4	CNS cancer	0.0	1.2
			(neuro;met) SK-N-
			AS
Lung ca. NCI-	0.0	0.0	CNS cancer (astro)	0.0	0.0
N417			SF-539
Lung ca. LX-1	0.0	0.0	CNS cancer (astro)	0.5	0.0
			SNB-75
Lung ca. NCI-	2.4	5.4	CNS cancer (glio)	0.0	0.0
H146			SNB-19
Lung ca. SHP-	17.0	47.3	CNS cancer (glio)	0.0	0.0
77			SF-295
Lung ca. A549	0.0	0.0	Brain (Amygdala)	2.8	2.9
			Pool
Lung ca. NCI-	0.0	0.0	Brain (cerebellum)	0.9	1.5
H526
Lung ca. NCI-	0.0	0.0	Brain (fetal)	2.3	3.1
H23
Lung ca. NCI-	0.5	0.7	Brain	3.7	6.7
H460			(Hippocampus)
			Pool
Lung ca. HOP-	0.3	3.1	Cerebral Cortex	7.7	16.2
62			Pool
Lung ca. NCI-	0.2	0.0	Brain (Substantia	4.6	8.1
H522			nigra) Pool
Liver	0.0	0.0	Brain (Thalamus)	8.8	17.9
			Pool
Fetal Liver	0.0	0.0	Brain (whole)	3.0	2.6
Liver ca.	0.0	0.0	Spinal Cord Pool	2.2	2.7
HepG2
Kidney Pool	6.3	6.5	Adrenal Gland	0.0	0.0
Fetal Kidney	2.1	0.5	Pituitary gland	0.0	0.4
			Pool
Renal ca. 786-0	0.0	0.0	Salivary Gland	0.0	0.0
Renal ca. A498	0.3	0.7	Thyroid (female)	0.0	0.6
Renal ca.	0.0	0.0	Pancreatic ca.	0.0	0.0
ACHN			CAPAN2
Renal ca. UO-	0.0	0.0	Pancreas Pool	1.4	4.7
31

[0843]

TABLE VF
General_screening_panel_v1.6
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag6865, Run		Ag6865, Run
Tissue Name	278387549	Tissue Name	278387549
Adipose	4.4	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	1.0
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	1.2
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell	0.0	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	6.3	Colon ca. HT29	0.5
Prostate ca.* (bone met)	0.4	Colon ca. HCT-116	0.0
PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	1.3	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	3.1
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	2.4
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.6
Ovary	0.9	Fetal Heart	100.0
Breast ca. MCF-7	0.0	Heart Pool	12.1
Breast ca. MDA-MB-	0.0	Lymph Node Pool	1.7
231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.7
Breast ca. T47D	0.0	Skeletal Muscle Pool	1.8
Breast ca. MDA-N	0.0	Spleen Pool	1.5
Breast Pool	0.0	Thymus Pool	1.6
Trachea	0.7	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.7	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	0.6	CNS cancer (neuro; met)	0.7
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-	0.0
		75
Lung ca. NCI-H146	2.5	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	16.5	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	3.6
Lung ca. NCI-H526	0.0	Brain (cerebellum)	4.2
Lung ca. NCI-H23	0.0	Brain (fetal)	3.6
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	2.7
Lung ca. HOP-62	1.5	Cerebral Cortex Pool	8.4
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	3.3
		Pool
Liver	0.0	Brain (Thalamus) Pool	7.9
Fetal Liver	0.6	Brain (whole)	1.1
Liver ca. HepG2	0.0	Spinal Cord Pool	2.4
Kidney Pool	5.9	Adrenal Gland	0.0
Fetal Kidney	1.8	Pituitary gland Pool	1.2
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	1.7	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0844] CNS_neurodegeneration_v1.0 Summary: Ag4329/Ag4330 Two experiments with two different probe and primer sets are in good agreement with significant expression of the CG106924-01 gene in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential use of this gene in treatment of central nervous system disorders.

[0845] General_screening_panel_v1.4 Summary: Ag4329/Ag4330 Two experiment with different probe and primer sets are in excellent agreements with highest expression of the CG106924-01 gene in fetal heart (CT=30.5-32). Interestingly, expression of this gene is higher in fetal as compared to the adult heart (CT=33.8-34.6). Therefore, expression of this gene may be used to distinguish fetal heart from adult tissue and also from other samples used in this panel. In addition, the relative overexpression of this gene in fetal heart suggests that the protein product may enhance heart growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of heart related diseases.

[0846] In addition, this gene is expressed at low levels in some of the regions of the central nervous system examined, including substantia nigra, thalamus, and cerebral cortex. This gene encodes a leucine-rich repeat protein. Leucine rich repeats (LRR) mediate reversible protein-protein interactions and have diverse cellular functions, including cellular adhesion and signaling. Several of these proteins, such as connectin, slit, chaoptin, and Toll have been shown to have a pivotal role in neuronal development in Drosophila, as well as a distinct role in neural development and in the adult nervous system of humans (Battye R., 2001, J. Neurosci. 21: 4290-4298; Itoh A., 1998, Brain Res. Mol. Brain Res. 62: 175-186). In Drosophilia, the LRR region of axon guidance proteins has been shown to be critical for their function (especially in axon repulsion). Since the leucine-rich-repeat protein encoded by this gene shows significant expression in the cerebral cortex, it is an excellent candidate neuronal guidance protein for axons, dendrites and/or growth cones in general. Therefore, therapeutic modulation of the levels of this protein, or possible signaling via this protein, may be of utility in enhancing/directing compensatory synaptogenesis and fiber growth in the CNS in response to neuronal death (stroke, head trauma), axon lesion (spinal cord injury), or neurodegeneration (Alzheimer's, Parkinson's, Huntington's, vascular dementia or any neurodegenerative disease).

[0847] General_screening_panel_v1.6 Summary: Ag6865 Highest expression of the CG106915-01 gene is detected in fetal heart (CT=30.2). Interestingly, expression of this gene is higher in fetal as compared to the adult heart (CT=33.3). Therefore, expression of this gene may be used to distinguish fetal heart from adult tissue and also from other samples used in this panel. In addition, the relative overexpression of this gene in fetal heart suggests that the protein product may enhance heart growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of heart related diseases.

[0848] In addition, this gene is expressed at low levels in some of the regions of the central nervous system examined, including thalamus, and cerebral cortex. Please see Panel 1.4 for a discussion of the potential use of this gene in treatment of central nervous system disorders.

[0849] Low expression of this gene is also seen in a lung cancer SHP-77 cell line. Therefore, expression of this gene may be used as a marker to detect the presence of lung cancer and therapeutic modulation of this gene may be useful in the treatment of this cancer.

[0850] Low expression of this gene is also seen in kidney, testis and adipose tissue. Therefore, therapeutic modulation of this gene may be useful in the treatment of diseases associated with these tissues including obesity, diabetes, lupus, glomerulonephritis, fertility and hypogonadism.

[0851] W. CG106942-01: Nramp-like Membrane Protein

[0852] Expression of gene CG106942-01 was assessed using the primer-probe set Ag4331, described in Table WA. Results of the RTQ-PCR runs are shown in Tables WB, WC and WD.

TABLE WA
Probe Name Ag4331
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gctgtttgtttggagtcgtcta-3′	22	1314	231
Probe	TET-5′-cttcttcggttaccgctgcttcaagg-3′-TAMRA	26	1339	232
Reverse	5′-aacagcaacccagtgagaaag-3′	21	1372	233

[0853]

TABLE WB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4331, Run		Ag4331, Run
Tissue Name	224344734	Tissue Name	224344734
AD 1 Hippo	8.8	Control (Path) 3	8.2
		Temporal Ctx
AD 2 Hippo	19.2	Control (Path) 4	18.8
		Temporal Ctx
AD 3 Hippo	13.2	AD 1 Occipital Ctx	1.2
AD 4 Hippo	10.9	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	56.6	AD 3 Occipital Ctx	5.1
AD 6 Hippo	40.9	AD 4 Occipital Ctx	13.3
Control 2 Hippo	29.3	AD 5 Occipital Ctx	8.5
Control 4 Hippo	13.4	AD 6 Occipital Ctx	36.3
Control (Path) 3 Hippo	1.8	Control 1 Occipital	2.8
		Ctx
AD 1 Temporal Ctx	7.1	Control 2 Occipital	59.5
		Ctx
AD 2 Temporal Ctx	20.2	Control 3 Occipital	2.2
		Ctx
AD 3 Temporal Ctx	5.8	Control 4 Occipital	8.9
		Ctx
AD 4 Temporal Ctx	9.5	Control (Path) 1	62.0
		Occipital Ctx
AD 5 Inf Temporal Ctx	68.8	Control (Path) 2	5.6
		Occipital Ctx
AD 5 SupTemporal Ctx	28.3	Control (Path) 3	2.1
		Occipital Ctx
AD 6 Inf Temporal Ctx	39.5	Control (Path) 4	13.8
		Occipital Ctx
AD 6 Sup Temporal Ctx	21.2	Control 1 Parietal Ctx	4.6
Control 1 Temporal Ctx	2.2	Control 2 Parietal Ctx	15.9
Control 2 Temporal Ctx	91.4	Control 3 Parietal Ctx	17.8
Control 3 Temporal Ctx	8.2	Control (Path) 1	100.0
		Parietal Ctx
Control 4 Temporal Ctx	8.4	Control (Path) 2	14.1
		Parietal Ctx
Control (Path) 1	37.1	Control (Path) 3	2.3
Temporal Ctx		Parietal Ctx
Control (Path) 2	4.1	Control (Path) 4	21.3
Temporal Ctx		Parietal Ctx

[0854]

TABLE WC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4331, Run		Ag4331, Run
Tissue Name	222556053	Tissue Name	222556053
Adipose	0.2	Renal ca. TK-10	31.0
Melanoma*	2.4	Bladder	3.8
Hs688(A).T
Melanoma*	1.2	Gastric ca. (liver met.)	4.2
Hs688(B).T		NCI-N87
Melanoma* M14	24.7	Gastric ca. KATO III	1.7
Melanoma* LOXIMVI	7.8	Colon ca. SW-948	0.7
Melanoma* SK-MEL-5	3.5	Colon ca. SW480	83.5
Squamous cell	3.1	Colon ca.* (SW480 met)	10.7
carcinoma SCC-4		SW620
Testis Pool	3.8	Colon ca. HT29	1.2
Prostate ca.* (bone met)	2.1	Colon ca. HCT-116	4.4
PC-3
Prostate Pool	2.0	Colon ca. CaCo-2	29.7
Placenta	4.0	Colon cancer tissue	24.0
Uterus Pool	0.2	Colon ca. SW1116	4.2
Ovarian ca. OVCAR-3	1.9	Colon ca. Colo-205	2.2
Ovarian ca. SK-OV-3	2.0	Colon ca. SW-48	17.9
Ovarian ca. OVCAR-4	7.6	Colon Pool	1.3
Ovarian ca. OVCAR-5	16.8	Small Intestine Pool	0.9
Ovarian ca. IGROV-1	12.8	Stomach Pool	2.0
Ovarian ca. OVCAR-8	7.1	Bone Marrow Pool	0.1
Ovary	4.7	Fetal Heart	1.8
Breast ca. MCF-7	11.7	Heart Pool	0.5
Breast ca. MDA-MB-	4.3	Lymph Node Pool	2.2
231
Breast ca. BT 549	10.4	Fetal Skeletal Muscle	0.8
Breast ca. T47D	51.8	Skeletal Muscle Pool	0.1
Breast ca. MDA-N	31.4	Spleen Pool	2.5
Breast Pool	1.7	Thymus Pool	1.6
Trachea	1.2	CNS cancer (glio/astro)	8.5
		U87-MG
Lung	1.0	CNS cancer (glio/astro) U-	6.8
		118-MG
Fetal Lung	1.6	CNS cancer (neuro; met)	21.6
		SK-N-AS
Lung ca. NCI-N417	60.3	CNS cancer (astro) SF-539	2.5
Lung ca. LX-1	13.6	CNS cancer (astro) SNB-	32.8
		75
Lung ca. NCI-H146	42.9	CNS cancer (glio) SNB-19	8.7
Lung ca. SHP-77	100.0	CNS cancer (glio) SF-295	2.0
Lung ca. A549	0.8	Brain (Amygdala) Pool	10.7
Lung ca. NCI-H526	58.2	Brain (cerebellum)	39.5
Lung ca. NCI-H23	4.0	Brain (fetal)	37.4
Lung ca. NCI-H460	9.5	Brain (Hippocampus) Pool	32.8
Lung ca. HOP-62	0.6	Cerebral Cortex Pool	26.6
Lung ca. NCI-H522	16.0	Brain (Substantia nigra)	34.9
		Pool
Liver	0.3	Brain (Thalamus) Pool	21.2
Fetal Liver	2.6	Brain (whole)	34.9
Liver ca. HepG2	64.6	Spinal Cord Pool	6.8
Kidney Pool	2.5	Adrenal Gland	8.2
Fetal Kidney	1.7	Pituitary gland Pool	3.6
Renal ca. 786-0	8.0	Salivary Gland	0.8
Renal ca. A498	18.4	Thyroid (female)	4.7
Renal ca. ACHN	11.3	Pancreatic ca. CAPAN2	1.6
Renal ca. UO-31	2.5	Pancreas Pool	4.3

[0855]

TABLE WD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4331, Run		Ag4331, Run
Tissue Name	183718671	Tissue Name	183718671
Secondary Th1 act	19.2	HUVEC IL-1beta	0.0
Secondary Th2 act	63.7	HUVEC IFN gamma	0.0
Secondary Tr1 act	13.2	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	4.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	1.5	Lung Microvascular EC none	0.0
Primary Th1 act	24.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	47.3	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	7.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	10.1
		TNF alpha + IL1beta
Primary Th2 rest	4.7	Small airway epithelium none	0.0
Primary Tr1 rest	11.8	Small airway epithelium	7.9
		TNF alpha + IL-1beta
CD45RA CD4	55.5	Coronery artery SMC rest	8.9
lymphocyte act
CD45RO CD4	25.3	Coronery artery SMC	8.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	21.3	Astrocytes rest	39.0
Secondary CD8	18.6	Astrocytes TNF alpha + IL-	25.3
lymphocyte rest		1beta
Secondary CD8	12.9	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	1.4
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	14.2	CCD1106 (Keratinocytes)	11.6
CD95 CH11		none
LAK cells rest	12.0	CCD1106 (Keratinocytes)	8.7
		TNF alpha + IL-1beta
LAK cells IL-2	25.3	Liver cirrhosis	6.9
LAK cells IL-2 + IL-12	15.3	NCI-H292 none	67.8
LAK cells IL-2 + IFN	27.2	NCI-H292 IL-4	100.0
gamma
LAK cells IL-2 + IL-18	6.6	NCI-H292 IL-9	75.3
LAK cells	0.0	NCI-H292 IL-13	50.7
PMA/ionomycin
NK Cells IL-2 rest	22.4	NCI-H292 IFN gamma	77.9
Two Way MLR 3 day	8.9	HPAEC none	0.0
Two Way MLR 5 day	23.5	HPAEC TNF alpha + IL-1beta	0.0
Two Way MLR 7 day	10.5	Lung fibroblast none	9.9
PBMC rest	0.0	Lung fibroblast TNF alpha +	50.0
		IL-1beta
PBMC PWM	52.5	Lung fibroblast IL-4	7.7
PBMC PHA-L	33.7	Lung fibroblast IL-9	13.3
Ramos (B cell) none	5.9	Lung fibroblast IL-13	17.4
Ramos (B cell) ionomycin	10.4	Lung fibroblast IFN gamma	26.6
B lymphocytes PWM	28.3	Dermal fibroblast CCD1070	28.9
		rest
B lymphocytes CD40L	18.0	Dermal fibroblast CCD1070	19.1
and IL-4		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	16.6
		IL-1beta
EOL-1 dbcAMP	2.3	Dermal fibroblast IFN gamma	13.0
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	26.6
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	22.1
Dendritic cells anti-CD40	0.0	Neutrophils TNF a + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	1.6
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	14.7
HUVEC none	0.0	Kidney	24.5
HUVEC starved	0.0

[0856] CNS_neurodegeneration_v1.0 Summary: Ag4331 This panel confirms the expression of the CG106942-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential use of this gene in treatment of central nervous system disorders.

[0857] General_screening_panel_v1.4 Summary: Ag4331 Highest expression of the CG106942-01 gene is detected in a lung cancer SHP-77 cell line (CT=28.5). High to moderate levels of expression of this gene is also seen in cluster of cancer cell lines including CNS, colon, renal, liver, breast, ovarian and melanoma cancer cell lines. Therefore, expression of this gene may be used as diagnostic marker for detection of these cancers and therapeutic modulation of this gene product may be beneficial in the treatment of these cancers.

[0858] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adrenal gland, thyroid, pituitary gland, fetal heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0859] Interestingly, expression of this gene is higher in fetal (CT=33.8) as compared to adult liver (CT=37). Therefore, expression of this gene may be used to distinguish the fetal tissue from the adult liver. In addition, the relative overexpression of this gene in fetal liver suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.

[0860] In addition, this gene is expressed at high to moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0861] Panel 4.1D Summary: Ag4331 Highest expression of the CG106942-01 gene is detected in IL4 treated NCI-H292 cells (CT=33.4). In addition, moderate to low expression of this gene is also seen in activated primary and secondary Th2 cells, activated CD45RA CD4 lymphocytes, PWM/PHA-L treated PBMC cells, resting astrocytes, untreated and cytokine treated NCI-H292 cells, TNF alpha+IL-1 beta treated lung fibroblasts. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of T cells and B cells mediated diseases such as systemic lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.

[0862] X. CG107513-01: Syntaxin Domain Containing Protein

[0863] Expression of gene CG107513-01 was assessed using the primer-probe set Ag4339, described in Table XA. Results of the RTQ-PCR runs are shown in Tables XB, XC and XD.

TABLE XA
Probe Name Ag4339
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gacgacaatgtggcagagtatc-3′	22	957	234
Probe	TET-5′-aaactggccaacaacgcggacaag-3′-TAMRA	24	981	235
Reverse	5′-tcttctcgaacacttgcttgat-3′	22	1020	236

[0864]

TABLE XB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4339, Run		Ag4339, Run
Tissue Name	224358973	Tissue Name	224358973
AD 1 Hippo	7.7	Control (Path) 3	2.7
		Temporal Ctx
AD 2 Hippo	16.5	Control (Path) 4	29.5
		Temporal Ctx
AD 3 Hippo	2.2	AD 1 Occipital Ctx	4.8
AD 4 Hippo	2.4	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	97.3	AD 3 Occipital Ctx	2.0
AD 6 Hippo	33.2	AD 4 Occipital Ctx	18.2
Control 2 Hippo	20.7	AD 5 Occipital Ctx	40.9
Control 4 Hippo	2.5	AD 6 Occipital Ctx	19.6
Control (Path) 3 Hippo	2.4	Control 1 Occipital Ctx	0.8
AD 1 Temporal Ctx	8.5	Control 2 Occipital Ctx	60.3
AD 2 Temporal Ctx	23.8	Control 3 Occipital Ctx	17.4
AD 3 Temporal Ctx	2.4	Control 4 Occipital Ctx	2.2
AD 4 Temporal Ctx	17.0	Control (Path) 1	100.0
		Occipital Ctx
AD 5 Inf Temporal Ctx	86.5	Control (Path) 2	15.7
		Occipital Ctx
AD 5 Sup Temporal	28.5	Control (Path) 3	1.4
Ctx		Occipital Ctx
AD 6 Inf Temporal Ctx	31.4	Control (Path) 4	19.8
		Occipital Ctx
AD 6 Sup Temporal	33.7	Control 1 Parietal Ctx	2.4
Ctx
Control 1 Temporal	1.8	Control 2 Parietal Ctx	31.0
Ctx
Control 2 Temporal	41.2	Control 3 Parietal Ctx	21.2
Ctx
Control 3 Temporal	16.6	Control (Path) 1	94.6
Ctx		Parietal Ctx
Control 3 Temporal	4.3	Control (Path) 2	22.7
Ctx		Parietal Ctx
Control (Path) 1	72.7	Control (Path) 3	2.2
Temporal Ctx		Parietal Ctx
Control (Path) 2	40.6	Control (Path) 4	47.6
Temporal Ctx		Parietal Ctx

[0865]

TABLE XC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4339, Run		Ag4339, Run
Tissue Name	222523508	Tissue Name	222523508
Adipose	0.7	Renal ca. TK-10	0.7
Melanoma*	0.9	Bladder	0.2
Hs688(A).T
Melanoma*	0.8	Gastric ca. (liver met.)	0.1
Hs688(B).T		NCI-N87
Melanoma* M14	12.1	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.1	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	31.2	Colon ca. SW480	3.5
Squamous cell	1.2	Colon ca.* (SW480 met)	0.4
carcinoma SCC-4		SW620
Testis Pool	0.4	Colon ca. HT29	0.0
Prostate ca.* (bone met)	4.3	Colon ca. HCT-116	1.4
PC-3
Prostate Pool	0.3	Colon ca. CaCo-2	0.2
Placenta	0.8	Colon cancer tissue	0.4
Uterus Pool	0.3	Colon ca. SW1116	0.7
Ovarian ca. OVCAR-3	1.9	Colon ca. Colo-205	0.1
Ovarian ca. SK-OV-3	1.6	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.7	Colon Pool	0.5
Ovarian ca. OVCAR-5	1.1	Small Intestine Pool	1.6
Ovarian ca. IGROV-1	1.3	Stomach Pool	0.3
Ovarian ca. OVCAR-8	1.2	Bone Marrow Pool	0.3
Ovary	0.8	Fetal Heart	1.3
Breast ca. MCF-7	0.1	Heart Pool	0.2
Breast ca. MDA-MB-	1.6	Lymph Node Pool	0.6
231
Breast ca. BT 549	5.3	Fetal Skeletal Muscle	1.3
Breast ca. T47D	1.7	Skeletal Muscle Pool	2.6
Breast ca. MDA-N	7.3	Spleen Pool	4.9
Breast Pool	0.6	Thymus Pool	0.8
Trachea	0.8	CNS cancer (glio/astro)	1.3
		U87-MG
Lung	0.2	CNS cancer (glio/astro) U-	1.5
		118-MG
Fetal Lung	11.7	CNS cancer (neuro; met)	3.2
		SK-N-AS
Lung ca. NCI-N417	0.7	CNS cancer (astro) SF-539	0.6
Lung ca. LX-1	0.2	CNS cancer (astro) SNB-	1.4
		75
Lung ca. NCI-H146	2.1	CNS cancer (glio) SNB-19	1.1
Lung ca. SHP-77	3.0	CNS cancer (glio) SF-295	2.9
Lung ca. A549	0.7	Brain (Amygdala) Pool	13.4
Lung ca. NCI-H526	0.9	Brain (cerebellum)	51.1
Lung ca. NCI-H23	1.3	Brain (fetal)	20.3
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	11.1
Lung ca. HOP-62	0.6	Cerebral Cortex Pool	16.8
Lung ca. NCI-H522	4.5	Brain (Substantia nigra)	13.8
		Pool
Liver	0.1	Brain (Thalamus) Pool	20.0
Fetal Liver	100.0	Brain (whole)	17.6
Liver ca. HepG2	0.0	Spinal Cord Pool	15.7
Kidney Pool	1.8	Adrenal Gland	2.4
Fetal Kidney	1.4	Pituitary gland Pool	1.7
Renal ca. 786-0	0.6	Salivary Gland	0.2
Renal ca. A498	1.2	Thyroid (female)	0.4
Renal ca. ACHN	2.0	Pancreatic ca. CAPAN2	0.1
Renal ca. UO-31	0.8	Pancreas Pool	0.4

[0866]

TABLE XD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4339, Run		Ag4339, Run
Tissue Name	184798183	Tissue Name	184798183
Secondary Th1 act	100.0	HUVEC IL-1beta	15.7
Secondary Th2 act	75.8	HUVEC IFN gamma	18.2
Secondary Tr1 act	59.0	HUVEC TNF alpha + IFN	53.2
		gamma
Secondary Th1 rest	23.0	HUVEC TNF alpha + IL4	9.9
Secondary Th2 rest	9.1	HUVEC IL-11	7.0
Secondary Tr1 rest	9.6	Lung Microvascular EC none	4.2
Primary Th1 act	92.0	Lung Microvascular EC	38.2
		TNF alpha + IL-1beta
Primary Th2 act	19.9	Microvascular Dermal EC	8.7
		none
Primary Tr1 act	33.0	Microsvasular Dermal EC	30.1
		TNF alpha + IL-1beta
Primary Th1 rest	3.1	Bronchial epithelium	11.7
		TNF alpha + IL1beta
Primary Th2 rest	1.9	Small airway epithelium none	2.7
Primary Tr1 rest	1.8	Small airway epithelium	1.2
		TNF alpha + IL-1beta
CD45RA CD4	38.4	Coronery artery SMC rest	8.1
lymphocyte act
CD45RO CD4	72.2	Coronery artery SMC	13.3
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	29.7	Astrocytes rest	16.2
Secondary CD8	18.3	Astrocytes TNF alpha + IL-	25.9
lymphocyte rest		1beta
Secondary CD8	16.7	KU-812 (Basophil) rest	47.0
lymphocyte act
CD4 lymphocyte none	4.9	KU-812 (Basophil)	61.6
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	25.2	CCD1106 (Keratinocytes)	19.6
CD95 CH11		none
LAK cells rest	3.1	CCD1106 (Keratinocytes)	12.7
		TNF alpha + IL-1beta
LAK cells IL-2	12.9	Liver cirrhosis	1.9
LAK cells IL-2 + IL-12	21.0	NCI-H292 none	5.0
LAK cells IL-2 + IFN	10.1	NCI-H292 IL-4	11.8
gamma
LAK cells IL-2 + IL-18	14.2	NCI-H292 IL-9	5.9
LAK cells	8.2	NCI-H292 IL-13	7.4
PMA/ionomycin
NK Cells IL-2 rest	14.3	NCI-H292 IFN gamma	2.2
Two Way MLR 3 day	13.7	HPAEC none	5.8
Two Way MLR 5 day	31.6	HPAEC TNF alpha + IL-1beta	35.4
Two Way MLR 7 day	14.4	Lung fibroblast none	25.0
PBMC rest	6.1	Lung fibroblast TNF alpha +	12.5
		IL-1beta
PBMC PWM	69.7	Lung fibroblast IL-4	11.4
PBMC PHA-L	33.4	Lung fibroblast IL-9	24.0
Ramos (B cell) none	8.8	Lung fibroblast IL-13	10.7
Ramos (B cell) ionomycin	8.6	Lung fibroblast IFN gamma	2.5
B lymphocytes PWM	58.6	Dermal fibroblast CCD1070	29.5
		rest
B lymphocytes CD40L	12.9	Dermal fibroblast CCD1070	12.8
and IL-4		TNF alpha
EOL-1 dbcAMP	6.5	Dermal fibroblast CCD1070	16.6
		IL-1beta
EOL-1 dbcAMP	3.2	Dermal fibroblast IFN gamma	2.9
PMA/ionomycin
Dendritic cells none	15.3	Dermal fibroblast IL-4	12.7
Dendritic cells LPS	85.3	Dermal Fibroblast rest	30.4
Dendritic cells anti-CD40	22.8	Neutrophils TNF a + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	6.9
Monocytes LPS	31.4	Colon	1.9
Macrophages rest	11.0	Lung	8.4
Macrophages LPS	17.8	Thymus	13.8
HUVEC none	12.1	Kidney	16.2
HUVEC starved	10.0

[0867] CNS_neurodegeneration_v1.0 Summary: Ag4339 This panel confirms the expression of the CG107513-01 gene at low levels in the brains of an independent group of individuals.

[0868] However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential use of this gene in treatment of central nervous system disorders.

[0869] General_screening_panel_v1.4 Summary: Ag4339 Highest expression of the CG107513-01 gene is detected in fetal liver (CT=24). Interestingly, this gene is expressed at much higher levels in fetal (CT=24) when compared to adult liver(CT=34.9). Thus expression of this gene can be used to distinguish fetal from adult liver and also from other samples used in this panel. In addition, the relative overexpression of this gene in fetal liver suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the membrane protein encoded by this gene may be useful in treatment of liver related diseases.

[0870] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0871] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of the membrane protein encoded by this gene may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0872] Panel 4.1D Summary: Ag4339 Highest expression of the CG107513-01 gene is detected in activated secondary Th1 cells (CT=30.7). This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0873] Y. CG107533-02: Tumor Necrosis Factor (Ligand) Superfamily, Member 7

[0874] Expression of gene CG107533-02 was assessed using the primer-probe set Ag6859, described in Table YA. Results of the RTQ-PCR runs are shown in Table YB.

TABLE YA
Probe Name Ag6859
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-agtcacttggggacctcag-3′	19	191	237
Probe	TET-5′-ctccttcctgcatggaccagagctg-3′-TAMRA	25	254	238
Reverse	5′-catcacgatggatacgtagct-3′	21	289	239

[0875]

TABLE YB
General_screening_panel_v1.6
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag6859, Run		Ag6859, Run
Tissue Name	278387508	Tissue Name	278387508
Adipose	0.3	Renal ca. TK-10	4.5
Melanoma*	0.0	Bladder	0.0
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.7	Gastric ca. KATO III	0.2
Melanoma* LOXIMVI	3.0	Colon ca. SW-948	5.8
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	2.5
Squamous cell	0.2	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	0.0	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	0.1
PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.5
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.2	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	57.8	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.1	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	0.2
Ovarian ca. IGROV-1	2.4	Stomach Pool	0.0
Ovarian ca. OVCAR-8	2.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-	0.0	Lymph Node Pool	0.0
231
Breast ca. BT 549	100.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.4	Spleen Pool	0.2
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer (glio/astro)	22.4
		U87-MG
Lung	0.1	CNS cancer (glio/astro) U-	21.5
		118-MG
Fetal Lung	0.0	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	1.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-	1.2
		75
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	1.9
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	7.1
Lung ca. A549	0.3	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	1.3	Brain (cerebellum)	0.0
Lung ca. NCI-H23	6.8	Brain (fetal)	0.0
Lung ca. NCI-H460	13.6	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	0.1	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.4
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.2
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.0
Kidney Pool	0.0	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	0.0
Renal ca. 786-0	44.1	Salivary Gland	0.0
Renal ca. A498	13.1	Thyroid (female)	0.0
Renal ca. ACHN	6.1	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	3.8	Pancreas Pool	0.0

[0876] General_screening_panel_v1.6 Summary: Ag6859 Highest expression of the CG107533-02 gene is detected in breast cancer BT 549 cell line (CT=29.4). In addition, moderate to low levels of expression of this gene is also seen in number of cancer cell lines derived from colon, lung, renal, breast, ovarian, melanoma and brain cancers. Interestingly, expression of this gene is low or undectable in the samples derived from normal tissues. Thus, expression of this gene may be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, lung, renal, breast, ovarian, melanoma and brain cancers.

[0877] Z. CG107562-01 and CG107562-02: TM LRR Ig FnIII Domains

[0878] Expression of gene CG107562-01 and CG107562-02 was assessed using the primer-probe set Ag4340, described in Table ZA. Results of the RTQ-PCR runs are shown in Tables ZB, ZC, ZD and ZE.

TABLE ZA
Probe Name Ag4340
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-agcttggtggacctgactctat-3′	22	605	240
Probe	TET-5′-ttttattacacctcatgctttcgctg-3′-TAMRA	26	643	241
Reverse	5′-aagccctcaaatttcgtaggt-3′	21	669	242

[0879]

TABLE ZB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag4340, Run	Ag4340, Run		Ag4340, Run	Ag4340, Run
Tissue Name	249266041	258587752	Tissue Name	249266041	258587752
AD 1 Hippo	4.4	3.7	Control (Path)	1.6	1.0
			3 Temporal
			Ctx
AD 2 Hippo	14.0	10.4	Control (Path)	23.7	21.5
			4 Temporal
			Ctx
AD 3 Hippo	2.4	1.6	AD 1	10.4	7.5
			Occipital Ctx
AD 4 Hippo	1.6	1.7	AD 2	0.0	0.0
			Occipital Ctx
			(Missing)
AD 5 hippo	100.0	100.0	AD 3	2.0	1.8
			Occipital Ctx
AD 6 Hippo	28.1	24.7	AD 4	8.7	7.1
			Occipital Ctx
Control 2 Hippo	15.3	9.4	AD 5	18.2	30.6
			Occipital Ctx
Control 4 Hippo	1.0	0.9	AD 6	45.1	25.5
			Occipital Ctx
Control (Path) 3	1.0	1.1	Control 1	0.9	0.4
Hippo			Occipital Ctx
AD 1 Temporal	3.1	3.3	Control 2	73.2	52.1
Ctx			Occipital Ctx
AD 2 Temporal	22.2	18.0	Control 3	8.8	10.4
Ctx			Occipital Ctx
AD 3 Temporal	0.8	1.7	Control 4	0.5	0.8
Ctx			Occipital Ctx
AD 4 Temporal	8.8	8.6	Control (Path)	68.8	66.0
Ctx			1 Occipital
			Ctx
AD 5 Inf	70.7	73.2	Control (Path)	8.5	9.6
Temporal Ctx			2 Occipital
			Ctx
AD 5	17.7	19.1	Control (Path)	0.8	0.4
SupTemporal Ctx			3 Occipital
			Ctx
AD 6 Inf	37.1	27.0	Control (Path)	10.6	9.8
Temporal Ctx			4 Occipital
			Ctx
AD 6 Sup	43.5	40.6	Control 1	2.0	1.2
Temporal Ctx			Parietal Ctx
Control 1	1.4	0.9	Control 2	27.4	20.3
Temporal Ctx			Parietal Ctx
Control 2	35.8	29.9	Control 3	13.5	12.2
Temporal Ctx			Parietal Ctx
Control 3	8.2	9.7	Control (Path)	71.2	70.7
Temporal Ctx			1 Parietal Ctx
Control 4	2.1	2.5	Control (Path)	17.4	15.1
Temporal Ctx			2 Parietal Ctx
Control (Path) 1	53.2	48.6	Control (Path)	1.1	0.8
Temporal Ctx			3 Parietal Ctx
Control (Path) 2	28.9	24.5	Control (Path)	33.9	35.6
Temporal Ctx			4 Parietal Ctx

[0880]

TABLE ZC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4340, Run		Ag4340, Run
Tissue Name	222523509	Tissue Name	222523509
Adipose	3.7	Renal ca. TK-10	7.6
Melanoma*	0.6	Bladder	1.5
Hs688(A).T
Melanoma*	0.3	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	24.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.3	Colon ca. SW480	0.0
Squamous cell	0.0	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	4.9	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	0.0
PC-3
Prostate Pool	9.0	Colon ca. CaCo-2	0.2
Placenta	1.0	Colon cancer tissue	1.5
Uterus Pool	3.8	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.2	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.5	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	2.0
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	12.4
Ovarian ca. IGROV-1	0.2	Stomach Pool	9.3
Ovarian ca. OVCAR-8	1.5	Bone Marrow Pool	11.3
Ovary	1.5	Fetal Heart	1.6
Breast ca. MCF-7	8.8	Heart Pool	2.4
Breast ca. MDA-MB-	0.0	Lymph Node Pool	37.6
231
Breast ca. BT 549	2.4	Fetal Skeletal Muscle	4.8
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.3
Breast ca. MDA-N	0.0	Spleen Pool	3.7
Breast Pool	9.9	Thymus Pool	14.2
Trachea	3.6	CNS cancer (glio/astro)	3.4
		U87-MG
Lung	1.8	CNS cancer (glio/astro) U-	76.8
		118-MG
Fetal Lung	11.9	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	7.7	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-	0.0
		75
Lung ca. NCI-H146	4.2	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	1.8	CNS cancer (glio) SF-295	8.8
Lung ca. A549	0.0	Brain (Amygdala) Pool	22.1
Lung ca. NCI-H526	0.0	Brain (cerebellum)	8.0
Lung ca. NCI-H23	1.0	Brain (fetal)	100.0
Lung ca. NCI-H460	3.3	Brain (Hippocampus) Pool	27.5
Lung ca. HOP-62	0.8	Cerebral Cortex Pool	55.9
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	34.4
		Pool
Liver	0.0	Brain (Thalamus) Pool	52.9
Fetal Liver	2.2	Brain (whole)	57.8
Liver ca. HepG2	0.0	Spinal Cord Pool	5.6
Kidney Pool	7.5	Adrenal Gland	9.1
Fetal Kidney	12.2	Pituitary gland Pool	1.6
Renal ca. 786-0	4.4	Salivary Gland	0.8
Renal ca. A498	0.0	Thyroid (female)	1.3
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	7.8

[0881]

TABLE ZD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4340, Run		Ag4340, Run
Tissue Name	186362025	Tissue Name	186362025
Secondary Th1 act	0.0	HUVEC IL-1beta	0.6
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	3.3
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.5
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC	5.2
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium	0.5
		TNF alpha + IL-1beta
CD45RA CD4	2.7	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	1.9
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha + IL-	9.2
lymphocyte rest		1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.7
lymphocyte act
CD4 lymphocyte none	1.0	KU-812 (Basophil)	3.8
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	5.8
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells	0.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	1.2
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1beta	21.9
Two Way MLR 7 day	0.0	Lung fibroblast none	10.2
PBMC rest	0.0	Lung fibroblast TNF alpha +	11.5
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	46.7
PBMC PHA-L	0.0	Lung fibroblast IL-9	48.3
Ramos (B cell) none	0.0	Lung fibroblast IL-13	58.2
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	38.2
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070	8.0
		rest
B lymphocytes CD40L	1.3	Dermal fibroblast CCD1070	19.5
and IL-4		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	14.2
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	3.7
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	5.9
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	8.1
Dendritic cells anti-CD40	0.0	Neutrophils TNF a + LPS	1.3
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	1.0
Macrophages rest	0.0	Lung	10.2
Macrophages LPS	0.0	Thymus	22.1
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[0882]

TABLE ZE
general oncology screening panel_v_2.4
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag4340, Run	Ag4340, Run		Ag4340, Run	Ag4340, Run
Tissue Name	258689189	260280474	Tissue Name	258689189	260280474
Colon cancer 1	0.7	1.7	Bladder cancer	0.0	0.9
			NAT 2
Colon NAT 1	0.9	1.3	Bladder cancer	0.0	0.2
			NAT 3
Colon cancer 2	0.8	3.9	Bladder cancer	37.1	14.1
			NAT 4
Colon cancer	1.3	1.2	Adenocarcinoma of	97.9	100.0
NAT 2			the prostate 1
Colon cancer 3	9.0	2.4	Adenocarcinoma of	2.4	3.4
			the prostate 2
Colon cancer	16.0	5.7	Adenocarcinoma of	14.2	5.5
NAT 3			the prostate 3
Colon	2.0	1.6	Adenocarcinoma of	12.5	5.1
malignant			the prostate 4
cancer 4
Colon normal	1.7	1.2	Prostate cancer	2.9	0.8
adjacent tissue 4			NAT 5
Lung cancer 1	1.1	0.7	Adenocarcinoma of	5.6	0.9
			the prostate 6
Lung NAT 1	0.0	0.7	Adenocarcinoma of	13.5	5.8
			the prostate 7
Lung cancer 2	100.0	51.1	Adenocarcinoma of	4.4	0.9
			the prostate 8
Lung NAT 2	1.7	0.8	Adenocarcinoma of	65.5	57.4
			the prostate 9
Squamous cell	2.8	1.5	Prostate cancer	2.3	0.9
carcinoma 3			NAT 10
Lung NAT 3	0.0	0.0	Kidney cancer 1	1.5	1.2
metastatic	24.1	8.8	KidneyNAT 1	2.4	0.8
melanoma 1
Melanoma 2	2.4	0.9	Kidney cancer 2	4.2	1.4
Melanoma 3	3.4	0.9	Kidney NAT 2	0.6	1.2
metastatic	46.7	11.1	Kidney cancer 3	0.0	0.3
melanoma 4
metastatic	17.6	10.6	Kidney NAT 3	0.0	0.8
melanoma 5
Bladder cancer 1	3.3	4.2	Kidney cancer 4	0.7	0.3
Bladder cancer	0.0	0.0	Kidney NAT 4	2.0	0.9
NAT 1
Bladder cancer 2	18.9	7.5

[0883] CNS_neurodegeneration_v1.0 Summary: Ag4340 Two experiments with the same probe and primer set produce results that are in excellent agreement. Highest expression of this gene is seen in the hippocampus of a patient with Alzheimer's disease (CTs=30). The hippocampus is a critical brain region for the formation of long-term memory. This gene encodes a putative LRR/Ig/FNII containing protein. Fibronectin repeat regions are often involved in cell surface binding and in this protein may be involved in the formation and maintenance of specific neuronal networks in the brain. Therefore, this gene product is therefore an excellent drug target for the treatment of dementia (Alzheimer's, vascular, etc) or for memory enhancement.

[0884] General_screening_panel_v1.4 Summary: Ag4340 Highest expression of this gene is seen in the fetal brain (CT=28.7). In addition, this gene is expressed at moderate levels in thalamus, substantia nigra, cerebral cortex, hippocampus, and amygdala, with low, but significant expression in the cerebellum. This gene encodes a novel transmembrane protein that contains a putative leucine rich repeat region. Leucine rich repeats (LRR) mediate reversible protein-protein interactions and have diverse cellular functions, including cellular adhesion and signaling. Several of these proteins, such as connectin, slit, chaoptin, and Toll have pivotal roles in neuronal development in Drosophila and may play significant but distinct roles in neural development and in the adult nervous system of humans (Battye R. (2001) J. Neurosci. 21: 4290-4298. Itoh A. (1998) Brain Res. Mol. Brain Res. 62: 175-186). In Drosophilia, the LRR region of axon guidance proteins has been shown to be critical for their function (especially in axon repulsion). (Taniguchi H, Shishido E, Takeichi M, Nose A. (2000) J Neurobiol. 42:104-116.) Since the leucine-rich-repeat protein encoded by this gene shows high expression in the cerebral cortex, it is an excellent candidate neuronal guidance protein for axons, dendrites and/or growth cones in general. Therefore, therapeutic modulation of the levels of this protein, or possible signaling via this protein, may be of utility in enhancing/directing compensatory synaptogenesis and fiber growth in the CNS in response to neuronal death (stroke, head trauma), axon lesion (spinal cord injury), or neurodegeneration (Alzheimer's, Parkinson's, Huntington's, vascular dementia or any neurodegenerative disease).

[0885] Among tissues with metabolic function, this gene is expressed at low but significant levels in pituitary, adipose, adrenal gland, pancreas, fetal skeletal muscle, and adult and fetal heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0886] Moderate levels of expression are also seen in colon cancer and some brain, breast, lung, renal, ovarian and melanoma cancer cell lines. Therefore, therapeutic modulation of this gene product may be useful in the treatment of these cancers.

[0887] Panel 4.1D Summary: Ag4340 Highest expression of this gene is seen in the kidney (CT=32). In addition, low but significant levels of expression are seen in activated lung and dermal fibroblasts, suggesting a role for this gene product in pathological and inflammatory conditions of the lung and skin.

[0888] general oncology screening panel_v—2.4 Summary: Ag4340 Two experiments with the same probe and primer set produce results that are in excellent agreement. Highest expression of the gene is seen in prostate and lung cancer (CTs=29.3-30). In addition, this gene is more highly expressed in lung and prostate cancer than in the corresponding normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers. Furthemore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of lung and prostate cancer.

[0889] AA. CG108184-01 and CG108184-02: Novel Transmembrane Protein Tm7

[0890] Expression of gene CG108184-01 and CG108184-02 was assessed using the primer-probe set Ag4350, described in Table AAA. Results of the RTQ-PCR runs are shown in Tables AAB, AAC and AAD. Please note that CG108184-02 represents a full-length physical clone of the CG108184-01 gene, validating the prediction of the gene sequence.

TABLE AAA
Probe Name Ag4350
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggttgtctggcttttaccttct-3′	22	1089	243
Probe	TET-5′-ttttccacaggatgcaccctggact-3′-TAMRA	25	1126	244
Reverse	5′-CTGTCTTGGGTAGGAACTGATG-3′	22	1153	245

[0891]

TABLE AAB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4350, Run		Ag4350,
Tissue Name	249266042	Tissue Name	Run 249266042
AD 1 Hippo	11.0	Control (Path) 3	5.2
		Temporal Ctx
AD 2 Hippo	22.4	Control (Path) 4	24.3
		Temporal Ctx
AD 3 Hippo	6.3	AD 1 Occipital Ctx	6.3
AD 4 Hippo	5.7	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	83.5	AD 3 Occipital Ctx	4.5
AD 6 Hippo	37.6	AD 4 Occipital Ctx	11.8
Control 2 Hippo	30.4	AD 5 Occipital Ctx	51.4
Control 4 Hippo	4.1	AD 6 Occipital Ctx	9.7
Control (Path) 3 Hippo	3.1	Control 1 Occipital Ctx	2.0
AD 1 Temporal Ctx	5.9	Control 2 Occipital Ctx	71.2
AD 2 Temporal Ctx	25.3	Control 3 Occipital Ctx	11.1
AD 3 Temporal Ctx	4.4	Control 4 Occipital Ctx	3.1
AD 4 Temporal Ctx	12.3	Control (Path) 1	80.7
		Occipital Ctx
AD 5 Inf Temporal Ctx	94.6	Control (Path) 2	6.6
		Occipital Ctx
AD 5 Sup Temporal	63.3	Control (Path) 3	1.3
Ctx		Occipital Ctx
AD 6 Inf Temporal Ctx	23.3	Control (Path) 4	7.7
		Occipital Ctx
AD 6 Sup Temporal	26.4	Control 1 Parietal Ctx	2.7
Ctx
Control 1 Temporal	2.4	Control 2 Parietal Ctx	29.1
Ctx
Control 2 Temporal	45.1	Control 3 Parietal Ctx	16.3
Ctx
Control 3 Temporal	10.2	Control (Path) 1	100.0
Ctx		Parietal Ctx
Control 3 Temporal	6.0	Control (Path) 2	13.7
Ctx		Parietal Ctx
Control (Path) 1	51.8	Control (Path) 3	2.3
Temporal Ctx		Parietal Ctx
Control (Path) 2	25.7	Control (Path) 4	32.5
Temporal Ctx		Parietal Ctx

[0892]

TABLE AAC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4350,		Ag4350,
Tissue Name	Run 222523514	Tissue Name	Run 222523514
Adipose	0.9	Renal ca. TK-10	2.5
Melanoma*	0.0	Bladder	12.3
Hs688(A).T
Melanoma*	0.1	Gastric ca. (liver met.)	8.5
Hs688(B).T		NCI-N87
Melanoma* M14	0.2	Gastric ca. KATO III	7.4
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.9
Melanoma* SK-MEL-5	1.3	Colon ca. SW480	0.8
Squamous cell	0.7	Colon ca.* (SW480 met)	0.8
carcinoma SCC-4		SW620
Testis Pool	2.2	Colon ca. HT29	1.5
Prostate ca.* (bone met)	2.3	Colon ca. HCT-116	4.0
PC-3
Prostate Pool	1.2	Colon ca. CaCo-2	1.4
Placenta	2.6	Colon cancer tissue	2.1
Uterus Pool	1.1	Colon ca. SW1116	1.5
Ovarian ca. OVCAR-3	1.5	Colon ca. Colo-205	0.7
Ovarian ca. SK-OV-3	1.5	Colon ca. SW-48	2.4
Ovarian ca. OVCAR-4	0.1	Colon Pool	1.0
Ovarian ca. OVCAR-5	6.1	Small Intestine Pool	2.6
Ovarian ca. IGROV-1	1.2	Stomach Pool	20.7
Ovarian ca. OVCAR-8	0.5	Bone Marrow Pool	1.1
Ovary	4.6	Fetal Heart	0.3
Breast ca. MCF-7	1.9	Heart Pool	0.4
Breast ca. MDA-MB-	0.0	Lymph Node Pool	1.9
231
Breast ca. BT 549	0.9	Fetal Skeletal Muscle	0.3
Breast ca. T47D	9.0	Skeletal Muscle Pool	0.4
Breast ca. MDA-N	0.2	Spleen Pool	1.2
Breast Pool	1.2	Thymus Pool	1.1
Trachea	34.9	CNS cancer (glio/astro)	0.7
		U87-MG
Lung	1.5	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	16.3	CNS cancer (neuro; met)	2.0
		SK-N-AS
Lung ca. NCI-N417	2.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	1.5	CNS cancer (astro) SNB-	0.2
		75
Lung ca. NCI-H146	0.3	CNS cancer (glio) SNB-19	1.1
Lung ca. SHP-77	1.4	CNS cancer (glio) SF-295	0.4
Lung ca. A549	2.9	Brain (Amygdala) Pool	74.7
Lung ca. NCI-H526	1.1	Brain (cerebellum)	55.9
Lung ca. NCI-H23	4.1	Brain (fetal)	10.5
Lung ca. NCI-H460	0.4	Brain (Hippocampus) Pool	66.9
Lung ca. HOP-62	0.1	Cerebral Cortex Pool	84.7
Lung ca. NCI-H522	7.8	Brain (Substantia nigra)	81.2
		Pool
Liver	0.2	Brain (Thalamus) Pool	100.0
Fetal Liver	2.1	Brain (whole)	96.6
Liver ca. HepG2	2.4	Spinal Cord Pool	7.9
Kidney Pool	3.7	Adrenal Gland	0.7
Fetal Kidney	10.4	Pituitary gland Pool	3.2
Renal ca. 786-0	0.9	Salivary Gland	20.7
Renal ca. A498	2.3	Thyroid (female)	1.9
Renal ca. ACHN	6.1	Pancreatic ca. CAPAN2	2.7
Renal ca. UO-31	5.5	Pancreas Pool	9.0

[0893]

TABLE AAD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4350,		Ag4350,
Tissue Name	Run 186362899	Tissue Name	Run 186362899
Secondary Th1 act	0.2	HUVEC IL-1beta	0.2
Secondary Th2 act	0.4	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.3	HUVEC TNF alpha + IFN	0.1
		gamma
Secondary Th1 rest	0.4	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.3	HUVEC IL-11	0.2
Secondary Tr1 rest	0.3	Lung Microvascular EC none	0.2
Primary Th1 act	0.3	Lung Microvascular EC	0.2
		TNF alpha + IL-1beta
Primary Th2 act	0.7	Microvascular Dermal EC	1.5
		none
Primary Tr1 act	0.7	Microsvasular Dermal EC	0.1
		TNF alpha + IL-1beta
Primary Th1 rest	0.1	Bronchial epithelium	0.2
		TNF alpha + IL1beta
Primary Th2 rest	0.8	Small airway epithelium none	0.5
Primary Tr1 rest	0.2	Small airway epithelium	0.1
		TNF alpha + IL-1beta
CD45RA CD4	1.2	Coronery artery SMC rest	0.6
lymphocyte act
CD45RO CD4	0.3	Coronery artery SMC	0.4
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.9	Astrocytes rest	0.0
Secondary CD8	0.6	Astrocytes TNF alpha + IL-	0.7
lymphocyte rest		1beta
Secondary CD8	0.5	KU-812 (Basophil) rest	0.5
lymphocyte act
CD4 lymphocyte none	0.1	KU-812 (Basophil)	0.3
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	1.9	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.3	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	0.8	Liver cirrhosis	0.3
LAK cells IL-2 + IL-12	0.6	NCI-H292 none	1.2
LAK cells IL-2 + IFN	0.6	NCI-H292 IL-4	0.9
gamma
LAK cells IL-2 + IL-18	0.1	NCI-H292 IL-9	2.9
LAK cells	0.2	NCI-H292 IL-13	1.3
PMA/ionomycin
NK Cells IL-2 rest	1.2	NCI-H292 IFN gamma	1.7
Two Way MLR 3 day	0.1	HPAEC none	0.4
Two Way MLR 5 day	0.7	HPAEC TNF alpha + IL-1beta	0.0
Two Way MLR 7 day	1.5	Lung fibroblast none	0.4
PBMC rest	0.0	Lung fibroblast TNF alpha +	0.4
		IL-1beta
PBMC PWM	0.7	Lung fibroblast IL-4	0.2
PBMC PHA-L	0.4	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.1
Ramos (B cell) ionomycin	0.9	Lung fibroblast IFN gamma	0.2
B lymphocytes PWM	0.5	Dermal fibroblast CCD1070	0.2
		rest
B lymphocytes CD40L	0.3	Dermal fibroblast CCD1070	0.6
and IL-4		TNF alpha
EOL-1 dbcAMP	0.2	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	0.3
PMA/ionomycin
Dendritic cells none	0.2	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.3
Dendritic cells anti-CD40	0.3	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.2	Neutrophils rest	0.2
Monocytes LPS	0.0	Colon	2.3
Macrophages rest	0.4	Lung	5.5
Macrophages LPS	0.0	Thymus	4.9
HUVEC none	0.4	Kidney	100.0
HUVEC starved	0.1

[0894] CNS_neurodegeneration_v1.0 Summary: Ag4350 This panel confirms the expression of the CG108184-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential use of this gene in treatment of central nervous system disorders.

[0895] General_screening_panel_v1.4 Summary: Ag4350 Higest expression of the CG108184-01 gene is detected in brain (CTs=28.1). High expression of this gene is seen mainly in all the brain regions examined. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0896] Moderate to low levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreas, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreas, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0897] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, thyroid, pituitary gland, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0898] Interestingly, this gene is expressed at much higher levels in fetal (CTs=30.7-33.7) when compared to adult lung and liver (CTs=34-37). This observation suggests that expression of this gene can be used to distinguish fetal lung and liver from corresponding adult tissues. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance growth or development of lung and liver in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the membrane protein encoded by this gene could be useful in treatment of lung and liver related diseases.

[0899] Panel 4.1D Summary: Ag4350 Higest expression of the CG108184-01 gene is detected in kidney (CT=27.8). Therefore, expression of this gene may be used to distinguish kidney from other samples used in this panel. Furthermore, therapeutic modulation of this gene product may be useful in the treatment of autoimmune and inflammatory disease that affect kidney, including lupus and glomerulonephritis.

[0900] In addition, moderate to low expression of this gene is also seen in CD45RA CD4 lymphocyte act, anti-CD95 CH11 treated secondary Th1/Th2/Tr1 cells, IL-2 treated LAK and NK cells, two way MLR, PWM treated PBMC, microvascular dermal EC, NCI-H292 and normal tissues represented by colon, lung and thymus. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis.

[0901] AB. CG108238-01: Sialic Acid Binding Immunoglobulin-like Lectin

[0902] Expression of gene CG108238-01 was assessed using the primer-probe set Ag4352, described in Table ABA. Results of the RTQ-PCR runs are shown in Tables ABB, ABC and ABD.

TABLE ABA
Probe Name Ag4352
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggacccctgactgaatcct-3′	19	1278	246
Probe	TET-5′-ctcccatggctgcctcctccttag-3′-TAMRA	24	1324	247
Reverse	5′-atgctggagctctccttctc-3′	20	1348	248

[0903]

TABLE ABB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4352,		Ag4352,
Tissue Name	Run 224367442	Tissue Name	Run 224367442
AD 1 Hippo	6.3	Control (Path) 3	1.7
		Temporal Ctx
AD 2 Hippo	12.2	Control (Path) 4	31.0
		Temporal Ctx
AD 3 Hippo	2.9	AD 1 Occipital Ctx	10.2
AD 4 Hippo	1.3	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	100.0	AD 3 Occipital Ctx	2.4
AD 6 Hippo	33.4	AD 4 Occipital Ctx	12.2
Control 2 Hippo	15.3	AD 5 Occipital Ctx	31.2
Control 4 Hippo	2.2	AD 6 Occipital Ctx	46.7
Control (Path) 3 Hippo	2.0	Control 1 Occipital	0.8
		Ctx
AD 1 Temporal Ctx	3.5	Control 2 Occipital	95.9
		Ctx
AD 2 Temporal Ctx	25.0	Control 3 Occipital	8.4
		Ctx
AD 3 Temporal Ctx	1.8	Control 4 Occipital	0.5
		Ctx
AD 4 Temporal Ctx	10.4	Control (Path) 1	82.9
		Occipital Ctx
AD 5 Inf Temporal Ctx	88.3	Control (Path) 2	10.5
		Occipital Ctx
AD 5 SupTemporal Ctx	22.2	Control (Path) 3	0.4
		Occipital Ctx
AD 6 Inf Temporal Ctx	42.6	Control (Path) 4	11.9
		Occipital Ctx
AD 6 Sup Temporal Ctx	57.4	Control 1 Parietal Ctx	3.2
Control 1 Temporal Ctx	0.9	Control 2 Parietal Ctx	31.0
Control 2 Temporal Ctx	41.8	Control 3 Parietal Ctx	15.1
Control 3 Temporal Ctx	9.0	Control (Path) 1	95.3
		Parietal Ctx
Control 4 Temporal Ctx	4.0	Control (Path) 2	18.2
		Parietal Ctx
Control (Path) 1	59.0	Control (Path) 3	1.8
Temporal Ctx		Parietal Ctx
Control (Path) 2	29.9	Control (Path) 4	36.3
Temporal Ctx		Parietal Ctx

[0904]

TABLE ABC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4352,		Ag4352,
Tissue Name	Run 222541798	Tissue Name	Run 222541798
Adipose	6.8	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	7.7
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell	0.0	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	100.0	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	0.0
PC-3
Prostate Pool	9.7	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	7.3	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	8.8
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	4.4
Ovarian ca. OVCAR-5	8.3	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	3.4
Ovary	0.0	Fetal Heart	10.2
Breast ca. MCF-7	0.0	Heart Pool	7.7
Breast ca. MDA-MB-	0.0	Lymph Node Pool	14.6
231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	11.7
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	23.3
Breast Pool	0.0	Thymus Pool	10.4
Trachea	5.3	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	2.2	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	4.5	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-	0.0
		75
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	15.8	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.0
Kidney Pool	0.0	Adrenal Gland	0.0
Fetal Kidney	11.2	Pituitary gland Pool	0.0
Renal ca. 786-0	33.4	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	10.6

[0905]

TABLE ABD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4352,		Ag4352,
Tissue Name	Run 186363976	Tissue Name	Run 186363976
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha + IL-	0.0
lymphocyte rest		1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	2.7
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN	1.5	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells	0.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1beta	0.0
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	4.0	Lung fibroblast TNF alpha +	0.0
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	7.6
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	1.9
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070	0.0
		rest
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070	0.0
and IL-4		TNF alpha
EOL-1 dbcAMP	1.6	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	1.7	Dermal fibroblast IFN gamma	0.0
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	3.5
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	18.9	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	3.6
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	21.2
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[0906] CNS_neurodegeneration_v1.0 Summary: Ag4352 This panel confirms the expression of the CG108238-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Expression of this gene in brain suggests that this gene may play a role in central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0907] General_screening_panel_v1.4 Summary: Ag4352 Low levels of expression of the CG108238-01 gene is seen only in testis (CT=34.5). Therefore, expression of this gene may be used to distinguish testis from other samples used in the panel. In addition, therapeutic modulation of this gene product may a beneficial in the treatment of testis related diseases including fertility and hypogonadism.

[0908] Panel 4.1D Summary: Ag4352 Low levels of expression of the CG108238-01 gene is seen only in kidney (CT=33.6). Therefore, expression of this gene may be used to distinguish kidney from other samples used in the panel. In addition, therapeutic modulation of this gene product may a beneficial in the treatment of autoimmune and inflammatory diseases that affect kidney including lupus and glomerulonephritis.

[0909] AC. CG109505-01: Aldehyde Dehydrogenase

[0910] Expression of gene CG109505-01 was assessed using the primer-probe set Ag4387, described in Table ACA. Results of the RTQ-PCR runs are shown in Tables ACB and ACC.

TABLE ACA
Probe Name Ag4387
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgtatccacagactgccagact-3′	22	744	249
Probe	TET-5′-tcgtccgaaacatacagtcctttcaca-3′-TAMRA	27	767	250
Reverse	5′-atgtcacaaaagttccgtgtgt-3′	22	797	252

[0911]

TABLE ACB
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4387,		Ag4387,
Tissue Name	Run 222567011	Tissue Name	Run 222567011
Adipose	0.5	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	7.8
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	4.6
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell	4.4	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	1.8	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	1.2
PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	15.9	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	2.8	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.4	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	100.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	1.1	Heart Pool	0.0
Breast ca. MDA-MB-	0.0	Lymph Node Pool	0.0
231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.7	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	0.0	Thymus Pool	1.3
Trachea	10.1	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro) U-	0.6
		118-MG
Fetal Lung	0.4	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-	0.0
		75
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	1.7	Brain (Amygdala) Pool	0.5
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	1.5	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.0
Kidney Pool	0.7	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	0.0
Renal ca. 786-0	0.5	Salivary Gland	2.4
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0912]

TABLE ACC
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4387,		Ag4387,
Tissue Name	Run 186501500	Tissue Name	Run 186501500
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.9
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.3	Bronchial epithelium	4.6
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	20.0
Primary Tr1 rest	0.0	Small airway epithelium	22.4
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha + IL-	0.0
lymphocyte rest		1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	6.7
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	16.3
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.4
CD95 CH11		none
LAK cells rest	0.6	CCD1106 (Keratinocytes)	2.5
		TNF alpha + IL-1beta
LAK cells IL-2	1.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.9	NCI-H292 none	0.4
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	0.9
gamma
LAK cells IL-2 + IL-18	0.9	NCI-H292 IL-9	0.0
LAK cells	0.6	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1beta	0.0
Two Way MLR 7 day	0.0	Lung fibroblast none	1.0
PBMC rest	0.0	Lung fibroblast TNF alpha +	0.4
		IL-1beta
PBMC PWM	0.9	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.8
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.5	Dermal fibroblast CCD1070	0.0
		rest
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070	0.0
and IL-4		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	0.0
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	1.8
Monocytes LPS	0.0	Colon	2.0
Macrophages rest	0.0	Lung	2.1
Macrophages LPS	0.0	Thymus	18.4
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[0913] General_screening_panel_v1.4 Summary: Ag4387 Highest expression of the CG109505-01 gene is detected in bone marrow (CT=30.6). Therefore, expression of this gene may be used to distinguish this sample from other samples used in this panel. In addition, therapeutic modulation of this gene product may be useful in the bone marrow related diseases such as leukemia.

[0914] Panel 4.1D Summary: Ag4387 Highest expression of the CG109505-01 gene is detected in kidney (CT=30.9). Therefore, expression of this gene may be used to distinguish kidney from other samples used in this panel. In addition, therapeutic modulation of this gene may be beneficial in the treatment of autoimmune of inflammatory disease that affect kidney including lupus and glomerulonephritis.

[0915] Moderate to low levels of expression of this gene is also seen in thymus, basophils, and small airway epithelium. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of asthma, allergies, COPD, and emphysema, inflammatory bowel disease, and autoimmune diseases.

[0916] AD. CG109742-01: Latent Transforming Growth Factor Beta Binding Protein 3 Like

[0917] Expression of gene CG109742-01 was assessed using the primer-probe sets Ag1112 and Ag25, described in Tables ADA. Results of the RTQ-PCR runs are shown in Table ADB.

TABLE ADA
Probe Name Ag25
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gtctgtgctgtggccgttct-3′	20	242	252
Probe	TET-5′-cagcagggctccaacatgacgct-3′-TAMRA	23	211	253
Reverse	5′-acctgtctcaagggccagtgt-3′	21	178	254

[0918]

TABLE ADB
Panel 1
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag25, Run		Ag25, Run
Tissue Name	91010022	Tissue Name	91010022
Endothelial cells	7.4	Renal ca. 786-0	3.8
Endothelial cells (treated)	1.8	Renal ca. A498	6.9
Pancreas	17.7	Renal ca. RXF 393	30.1
Pancreatic ca. CAPAN 2	9.6	Renal ca. ACHN	9.9
Adrenal gland	11.6	Renal ca. UO-31	5.7
Thyroid	14.8	Renal ca. TK-10	19.8
Salivary gland	6.7	Liver	34.4
Pituitary gland	7.7	Liver (fetal)	2.4
Brain (fetal)	5.3	Liver ca. (hepatoblast)	8.8
		HepG2
Brain (whole)	19.2	Lung	15.0
Brain (amygdala)	7.2	Lung (fetal)	19.3
Brain (cerebellum)	52.9	Lung ca. (small cell) LX-1	22.1
Brain (hippocampus)	7.6	Lung ca. (small cell)	0.8
		NCI-H69
Brain (substantia nigra)	6.9	Lung ca. (s. cell var.)	1.8
		SHP-77
Brain (thalamus)	6.8	Lung ca. (large cell)NCI-	13.3
		H460
Brain (hypothalamus)	10.8	Lung ca. (non-sm. cell)	15.0
		A549
Spinal cord	11.8	Lung ca. (non-s. cell)	4.1
		NCI-H23
glio/astro U87-MG	7.1	Lung ca. (non-s. cell)	0.0
		HOP-62
glio/astro U-118-MG	5.1	Lung ca. (non-s. cl) NCI-	1.6
		H522
astrocytoma SW1783	2.7	Lung ca. (squam.) SW	100.0
		900
neuro*; met SK-N-AS	2.6	Lung ca. (squam.) NCI-	0.4
		H596
astrocytoma SF-539	1.9	Mammary gland	50.3
astrocytoma SNB-75	5.1	Breast ca.* (pl. ef) MCF-7	7.4
glioma SNB-19	10.4	Breast ca.* (pl. ef) MDA-	0.9
		MB-231
glioma U251	18.3	Breast ca.* (pl. ef) T47D	12.0
glioma SF-295	27.5	Breast ca. BT-549	16.4
Heart	20.4	Breast ca. MDA-N	3.7
Skeletal muscle	5.1	Ovary	59.0
Bone marrow	3.2	Ovarian ca. OVCAR-3	3.5
Thymus	17.7	Ovarian ca. OVCAR-4	6.3
Spleen	6.9	Ovarian ca. OVCAR-5	49.0
Lymph node	16.8	Ovarian ca. OVCAR-8	7.6
Colon (ascending)	3.6	Ovarian ca. IGROV-1	1.1
Stomach	20.2	Ovarian ca. (ascites) SK-	1.2
		OV-3
Small intestine	8.5	Uterus	9.9
Colon ca. SW480	0.5	Placenta	21.0
Colon ca.* SW620	1.9	Prostate	15.4
(SW480 met)
Colon ca. HT29	2.5	Prostate ca.* (bone met)	7.8
		PC-3
Colon ca. HCT-116	0.0	Testis	25.7
Colon ca. CaCo-2	4.3	Melanoma Hs688(A).T	4.4
Colon ca. HCT-15	3.8	Melanoma* (met)	14.6
		Hs688(B).T
Colon ca. HCC-2998	0.8	Melanoma UACC-62	3.3
Gastric ca.* (liver met)	39.8	Melanoma M14	5.5
NCI-N87
Bladder	18.6	Melanoma LOX IMVI	90.8
Trachea	21.3	Melanoma* (met) SK-	0.0
		MEL-5
Kidney	16.4	Melanoma SK-MEL-28	3.2
Kidney (fetal)	23.3

[0919] Panel 1 Summary: Ag25 Highest expression of the CG109742-01 gene is detected in a lung cancer SW 900 cell line (CT=21.5). High expression of this gene is seen in cluster of cancer cell lines including melanoma, ovarian, breast, lung, renal, colon, gastric, pancreatic and CNS cancer cell lines. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of these cancers.

[0920] Among tissues with metabolic or endocrine function, this gene is expressed at high levels in pancreas, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0921] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0922] AE. CG109844-01: C4B-Binding Protein

[0923] Expression of gene CG109844-01 was assessed using the primer-probe sets Ag4406 and Ag4446, described in Tables AEA and AEB. Results of the RTQ-PCR runs are shown in Table AEC.

TABLE ABA
Probe Name Ag4406
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tatcctcagaggcagcagttta-3′	22	825	255
Probe	TET-5′-tggtatccttctgttccctcttgcag-3′-TAMRA	26	871	256
Reverse	5′-taggacagtgcaaccattcact-3′	22	897	257

[0924]

TABLE AEB
Probe Name Ag4446
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tatcctcagaggcagcagttta-3′	22	825	258
Probe	TET-5′-tggtatccttctgttccctcttgcag-3′-TAMRA	26	871	259
Reverse	5′-taggacagtgcaaccattcact-3′	22	897	260

[0925]

TABLE AEC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4446,		Ag4446,
Tissue Name	Run 222693980	Tissue Name	Run 222693980
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	0.0
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	9.3
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	14.4
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell	0.0	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	34.6	Colon ca. HT29	0.0
Prostate ca.* (bone met)	18.3	Colon ca. HCT-116	100.0
PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	13.4	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-	0.0	Lymph Node Pool	0.0
231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	11.2	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer (glio/astro)	10.2
		U87-MG
Lung	0.0	CNS cancer (glio/astro) U-	56.3
		118-MG
Fetal Lung	0.0	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-	0.0
		75
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.0	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	0.0
Kidney Pool	0.0	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	0.0
Renal ca. 786-0	22.2	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0926] General_screening_panel_v1.4 Summary: Ag4406 Low levels of expression of the CG109844-01 gene is seen only in a colon cancer HCT-116 cell line (CT=34.9). Therefore, expression of this gene may be used to distinguish this sample from other samples used in this panel and also as diagnostic marker for colon cancer. In addition, therapeutic modulation of this gene product may be beneficial for the treatment of colon cancer.

[0927] AF. CG110014-03: Protein Tyrosine Kinase-7

[0928] Expression of gene CG110014-03 was assessed using the primer-probe set Ag6098, described in Table AFA. Results of the RTQ-PCR runs are shown in Table AFB.

TABLE AFA
Probe Name Ag6098
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gcaccctcgatgaaagct-3′	18	482	261
Probe	TET-5′-atacctcgctactaccacgtcctggg-3′-TAMRA	26	521	262
Reverse	5′-agaactggcaatggaacatg-3′	20	555	263

[0929]

TABLE AFB
General_screening_panel_v1.5
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag6098,		Ag6098,
Tissue Name	Run 248491181	Tissue Name	Run 248491181
Adipose	0.0	Renal ca. TK-10	15.8
Melanoma*	46.7	Bladder	6.2
Hs688(A).T
Melanoma*	19.6	Gastric ca. (liver met.)	22.7
Hs688(B).T		NCI-N87
Melanoma* M14	7.4	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	2.7	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	5.8	Colon ca. SW480	20.7
Squamous cell	20.4	Colon ca.* (SW480 met)	39.5
carcinoma SCC-4		SW620
Testis Pool	5.6	Colon ca. HT29	3.8
Prostate ca.* (bone met)	10.7	Colon ca. HCT-116	100.0
PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	26.8
Placenta	21.5	Colon cancer tissue	10.0
Uterus Pool	5.7	Colon ca. SW1116	16.8
Ovarian ca. OVCAR-3	25.9	Colon ca. Colo-205	4.8
Ovarian ca. SK-OV-3	25.7	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	9.9	Colon Pool	6.0
Ovarian ca. OVCAR-5	8.6	Small Intestine Pool	9.3
Ovarian ca. IGROV-1	11.0	Stomach Pool	4.3
Ovarian ca. OVCAR-8	6.8	Bone Marrow Pool	2.2
Ovary	19.1	Fetal Heart	1.3
Breast ca. MCF-7	3.4	Heart Pool	9.1
Breast ca. MDA-MB-	10.0	Lymph Node Pool	10.8
231
Breast ca. BT 549	46.7	Fetal Skeletal Muscle	12.2
Breast ca. T47D	2.7	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	5.8	Spleen Pool	5.2
Breast Pool	13.6	Thymus Pool	29.3
Trachea	1.6	CNS cancer (glio/astro)	0.8
		U87-MG
Lung	0.0	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	35.8	CNS cancer (neuro; met)	20.0
		SK-N-AS
Lung ca. NCI-N417	4.5	CNS cancer (astro) SF-539	80.7
Lung ca. LX-1	40.1	CNS cancer (astro) SNB-	39.5
		75
Lung ca. NCI-H146	5.3	CNS cancer (glio) SNB-19	3.7
Lung ca. SHP-77	24.3	CNS cancer (glio) SF-295	49.7
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	6.3	Brain (cerebellum)	32.5
Lung ca. NCI-H23	27.5	Brain (fetal)	7.3
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	8.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	7.8	Brain (Substantia nigra)	1.1
		Pool
Liver	0.0	Brain (Thalamus) Pool	2.8
Fetal Liver	1.1	Brain (whole)	5.3
Liver ca. HepG2	34.6	Spinal Cord Pool	57.0
Kidney Pool	13.2	Adrenal Gland	0.7
Fetal Kidney	39.8	Pituitary gland Pool	2.7
Renal ca. 786-0	0.0	Salivary Gland	1.4
Renal ca. A498	0.0	Thyroid (female)	0.7
Renal ca. ACHN	4.6	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	7.0	Pancreas Pool	6.0

[0930] General_screening_panel_v1.5 Summary: Ag6098 Highest expression of the CG110014-03 gene is detected in colon cancer HCT-116 cell line (CT=32.9). In addition, low to moderate expression of this gene is also seen in number of cancer cell lines including CNS, colon, liver, lung, breast, ovarain and melanoma cancer cell lines. This gene codes for a splice variant of tyrosine protein kinase-like 7 precursor (colon carcinoma kinase 4, CCK-4; PTK7), belonging to protein-tyrosine kinases (PTKs) family. PTKs play important role in regulating cell proliferation and differentiation during development. Mossie et al. (1995, Oncogene 11(10):2179-84, PMID: 7478540) showed a varied expression of CCK-4 in colon cancer cell lines and suggested a tumor-characteristic role for CCK-4 as a signal amplifier or modulator. Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of melanoma, CNS, colon, liver, lung, breast, and ovarian cancers.

[0931] Moderate expression of this gene is also seen in spinal cord sample. Therefore, therapeutic modulation of this gene product may be useful in the treatment of spinal cord related diseases.

[0932] Low expression of this gene is also detected in fetal lung. Interestingly, expression of this gene is higher in fetal (CT=34.3) as compared to adult lung (CT=40). Therefore, the expression of this gene may be used to distinguish the fetal from adult lung. In addition, the relative overexpression of this gene in fetal lung suggests that the protein product may enhance lung growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the CCK-4 protein encoded by this gene could be useful in treatment of lung related diseases.

[0933] AG. CG110014-04: Protein Tyrosine Kinase-7

[0934] Expression of gene CG110014-04 was assessed using the primer-probe set Ag6687, described in Table AGA. Results of the RTQ-PCR runs are shown in Table AGB.

TABLE AGA
Probe Name Ag6687
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cacggttcgaggtgttcct-3′	19	1395	264
Probe	TET-5′-tacttgtgaagagcctgcagagcaaggat-3′-TAMRA	29	1458	265
Reverse	5′-tccacatattccagcaccatg-3′	21	1594	266

[0935]

TABLE AGB
General_screening_panel_v1.6
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag6687,		Ag6687,
Tissue Name	Run 277259294	Tissue Name	Run 277259294
Adipose	0.0	Renal ca. TK-10	30.6
Melanoma*	73.7	Bladder	4.7
Hs688(A).T
Melanoma*	63.7	Gastric ca. (liver met.)	28.5
Hs688(B).T		NCI-N87
Melanoma* M14	20.7	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	3.3	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	2.4	Colon ca. SW480	34.9
Squamous cell	8.7	Colon ca.* (SW480 met)	36.3
carcinoma SCC-4		SW620
Testis Pool	1.4	Colon ca. HT29	9.3
Prostate ca.* (bone met)	12.2	Colon ca. HCT-116	33.2
PC-3
Prostate Pool	2.7	Colon ca. CaCo-2	27.5
Placenta	6.2	Colon cancer tissue	14.0
Uterus Pool	0.7	Colon ca. SW1116	37.6
Ovarian ca. OVCAR-3	27.9	Colon ca. Colo-205	0.8
Ovarian ca. SK-OV-3	55.1	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	21.2	Colon Pool	10.2
Ovarian ca. OVCAR-5	2.7	Small Intestine Pool	7.1
Ovarian ca. IGROV-1	13.7	Stomach Pool	8.4
Ovarian ca. OVCAR-8	19.5	Bone Marrow Pool	1.1
Ovary	15.5	Fetal Heart	0.6
Breast ca. MCF-7	5.9	Heart Pool	5.0
Breast ca. MDA-MB-	26.1	Lymph Node Pool	12.8
231
Breast ca. BT 549	71.7	Fetal Skeletal Muscle	0.6
Breast ca. T47D	8.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	4.0
Breast Pool	12.6	Thymus Pool	18.8
Trachea	7.3	CNS cancer (glio/astro)	4.5
		U87-MG
Lung	2.3	CNS cancer (glio/astro) U-	3.5
		118-MG
Fetal Lung	22.8	CNS cancer (neuro; met)	33.4
		SK-N-AS
Lung ca. NCI-N417	3.0	CNS cancer (astro) SF-539	64.6
Lung ca. LX-1	59.9	CNS cancer (astro) SNB-	100.0
		75
Lung ca. NCI-H146	9.9	CNS cancer (glio) SNB-19	22.4
Lung ca. SHP-77	8.9	CNS cancer (glio) SF-295	82.9
Lung ca. A549	2.1	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	6.8	Brain (cerebellum)	1.7
Lung ca. NCI-H23	16.5	Brain (fetal)	3.3
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	17.6	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	15.4	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	1.1	Brain (whole)	2.2
Liver ca. HepG2	12.2	Spinal Cord Pool	0.0
Kidney Pool	22.7	Adrenal Gland	0.0
Fetal Kidney	13.0	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	3.8
Renal ca. A498	0.0	Thyroid (female)	5.6
Renal ca. ACHN	14.1	Pancreatic ca. CAPAN2	4.8
Renal ca. UO-31	26.2	Pancreas Pool	0.0

[0936] General_screening_panel_v1.6 Summary: Ag6687 Highest expression of the CG110014-04 gene is detected in CNS cancer cell line SNB-75 (CT=32.6). In addition, moderate to low levels of expression of this gene is also seen in number of cancer cell lines derived from gastric, colon, lung, renal, breast, ovarian, melanoma and brain cancers. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of gastric, colon, lung, renal, breast, ovarian, melanoma and brain cancers.

[0937] Low levels of expression of this gene is also seen in kidney and fetal lung. Interestingly, this gene is expressed at much higher levels in fetal (CT=34.7) when compared to adult lung (CT=38). This observation suggests that expression of this gene can be used to distinguish fetal from adult lung. In addition, the relative overexpression of this gene in fetal lung suggests that the protein product may enhance lung growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of lung and kidney related diseases.

[0938] AH. CG110187-01: Novel Alpha C1-like Protocadherin

[0939] Expression of gene CG110187-01 was assessed using the primer-probe set Ag4412, described in Table AHA. Results of the RTQ-PCR runs are shown in Tables AHB, AHC, AHD, AHE and AHF.

TABLE AHA
Probe Name Ag4412
			Start	SEQ ID
Primers	Sequences	Length	Position	No.
Forward	5′-gctttctgcccagaacttgtat-3′	22	2029	267
Probe	TET-5′-aattgccttggcttgtatttcctttt-3′-TAMRA	26	2056	268
Reverse	5′-aagaaaagtaagcaccccagaa-3′	22	2085	269

[0940]

TABLE AHB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4412, Run		Ag4412,
Tissue Name	224505948	Tissue Name	Run 224505948
AD 1 Hippo	8.1	Control (Path) 3	2.0
		Temporal Ctx
AD 2 Hippo	11.9	Control (Path) 4	21.3
		Temporal Ctx
AD 3 Hippo	4.9	AD 1 Occipital Ctx	10.2
AD 4 Hippo	1.2	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	76.8	AD 3 Occipital Ctx	4.2
AD 6 Hippo	39.8	AD 4 Occipital Ctx	11.3
Control 2 Hippo	11.2	AD 5 Occipital Ctx	29.9
Control 4 Hippo	4.6	AD 6 Occipital Ctx	12.6
Control (Path) 3 Hippo	1.9	Control 1 Occipital Ctx	1.6
AD 1 Temporal Ctx	4.4	Control 2 Occipital Ctx	65.1
AD 2 Temporal Ctx	23.2	Control 3 Occipital Ctx	7.5
AD 3 Temporal Ctx	2.7	Control 4 Occipital Ctx	0.0
AD 4 Temporal Ctx	10.7	Control (Path) 1	73.7
		Occipital Ctx
AD 5 Inf Temporal Ctx	66.0	Control (Path) 2	15.5
		Occipital Ctx
AD 5 Sup Temporal	14.3	Control (Path) 3	1.6
Ctx		Occipital Ctx
AD 6 Inf Temporal Ctx	33.7	Control (Path) 4	9.2
		Occipital Ctx
AD 6 Sup Temporal	36.3	Control 1 Parietal Ctx	3.8
Ctx
Control 1 Temporal	4.6	Control 2 Parietal Ctx	26.2
Ctx
Control 2 Temporal	36.3	Control 3 Parietal Ctx	12.7
Ctx
Control 3 Temporal	12.0	Control (Path) 1	100.0
Ctx		Parietal Ctx
Control 3 Temporal	2.1	Control (Path) 2	22.8
Ctx		Parietal Ctx
Control (Path) 1	48.0	Control (Path) 3	2.4
Temporal Ctx		Parietal Ctx
Control (Path) 2	41.8	Control (Path) 4	7.5
Temporal Ctx		Parietal Ctx

[0941]

TABLE AHC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4412,		Ag4412,
Tissue Name	Run 219923005	Tissue Name	Run 219923005
Adipose	1.5	Renal ca. TK-10	2.3
Melanoma*	0.3	Bladder	5.0
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.7	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	2.0	Colon ca. SW480	0.4
Squamous cell	0.0	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	6.7	Colon ca. HT29	0.0
Prostate ca.* (bone met)	95.9	Colon ca. HCT-116	3.9
PC-3
Prostate Pool	0.2	Colon ca. CaCo-2	0.1
Placenta	0.0	Colon cancer tissue	0.9
Uterus Pool	0.5	Colon ca. SW1116	0.5
Ovarian ca. OVCAR-3	9.5	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	27.2	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.3	Colon Pool	4.2
Ovarian ca. OVCAR-5	1.5	Small Intestine Pool	6.4
Ovarian ca. IGROV-1	2.0	Stomach Pool	3.3
Ovarian ca. OVCAR-8	5.4	Bone Marrow Pool	0.7
Ovary	2.4	Fetal Heart	0.0
Breast ca. MCF-7	12.6	Heart Pool	1.6
Breast ca. MDA-MB-	0.2	Lymph Node Pool	5.4
231
Breast ca. BT 549	4.5	Fetal Skeletal Muscle	0.0
Breast ca. T47D	7.9	Skeletal Muscle Pool	0.3
Breast ca. MDA-N	2.1	Spleen Pool	1.0
Breast Pool	6.0	Thymus Pool	6.1
Trachea	3.3	CNS cancer (glio/astro)	0.2
		U87-MG
Lung	0.8	CNS cancer (glio/astro) U-	0.2
		118-MG
Fetal Lung	2.8	CNS cancer (neuro; met)	31.6
		SK-N-AS
Lung ca. NCI-N417	1.1	CNS cancer (astro) SF-539	1.7
Lung ca. LX-1	0.3	CNS cancer (astro) SNB-	16.6
		75
Lung ca. NCI-H146	9.2	CNS cancer (glio) SNB-19	1.6
Lung ca. SHP-77	27.7	CNS cancer (glio) SF-295	1.5
Lung ca. A549	6.3	Brain (Amygdala) Pool	6.7
Lung ca. NCI-H526	0.0	Brain (cerebellum)	25.3
Lung ca. NCI-H23	20.2	Brain (fetal)	100.0
Lung ca. NCI-H460	9.5	Brain (Hippocampus) Pool	4.5
Lung ca. HOP-62	0.9	Cerebral Cortex Pool	8.6
Lung ca. NCI-H522	37.6	Brain (Substantia nigra)	6.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	8.7
Fetal Liver	0.2	Brain (whole)	17.0
Liver ca. HepG2	0.4	Spinal Cord Pool	6.8
Kidney Pool	6.8	Adrenal Gland	1.1
Fetal Kidney	0.7	Pituitary gland Pool	3.6
Renal ca. 786-0	0.0	Salivary Gland	0.5
Renal ca. A498	2.4	Thyroid (female)	2.4
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	1.8
Renal ca. UO-31	1.3	Pancreas Pool	6.3

[0942]

TABLE AHD
Oncology_cell_line_screening_panel_v3.2
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4412,		Ag4412,
	Run		Run
Tissue Name	268695315	Tissue Name	268695315
94905_Daoy_Medulloblastoma/Cerebellum—	0.0	94954_Ca Ski_Cervical epidermoid	0.0
sscDNA		carcinoma (metastasis)_sscDNA
94906_TE671_Medulloblastom/Cerebellum—	1.3	94955_ES-2_Ovarian clear cell	0.0
sscDNA		carcinoma_sscDNA
94907_D283	12.4	94957_Ramos/6 h stim_Stimulated	0.0
Med_Medulloblastoma/Cerebellum_sscDNA		with PMA/ionomycin 6 h_sscDNA
94908_PFSK-1_Primitive	0.9	94958_Ramos/14 h stim_Stimulated	0.0
Neuroectodermal/Cerebellum_sscDNA		with PMA/ionomycin 14 h_sscDNA
94909_XF-498_CNS_sscDNA	2.9	94962_MEG-01_Chronic	0.0
		myelogenous leukemia
		(megokaryoblast)_sscDNA
94910_SNB-78_CNS/glioma_sscDNA	0.9	94963_Raji_Burkitt's	0.0
		lymphoma_sscDNA
94911_SF-	0.0	94964_Daudi_Burkitt's	0.0
268_CNS/glioblastoma_sscDNA		lymphoma_sscDNA
94912_T98G_Glioblastoma_sscDNA	0.0	94965_U266_B-cell	0.0
		plasmacytoma/myeloma_sscDNA
96776_SK-N-SH_Neuroblastoma	4.2	94968_CA46_Burkitt's	0.0
(metastasis)_sscDNA		lymphoma_sscDNA
94913_SF-	0.0	94970_RL_non-Hodgkin's B-cell	0.0
295_CNS/glioblastoma_sscDNA		lymphoma_sscDNA
132565_NT2 pool_sscDNA	11.2	94972_JM1_pre-B-cell	0.0
		lymphoma/leukemia_sscDNA	0.0
94914_Cerebellum_sscDNA	24.5	94973_Jurkat_T cell	0.0
		leukemia_sscDNA
96777_Cerebellum_sscDNA	13.5	94974_TF-	0.0
		1_Erythroleukemia_sscDNA
94916_NCI-H292_Mucoepidermoid lung	0.0	94975_HUT 78_T-cell	0.0
carcinoma_sscDNA		lymphoma_sscDNA
94917_DMS-114_Small cell lung	3.7	94977_U937_Histiocytic	0.0
cancer_sscDNA		lymphoma_sscDNA
94918_DMS-79_Small cell lung	100.0	94980_KU-812_Myelogenous	0.0
cancer/neuroendocrine_sscDNA		leukemia_sscDNA
94919_NCI-H146_Small cell lung	15.3	94981_769-P_Clear cell renal	0.0
cancer/neuroendocrine_sscDNA		carcinoma_sscDNA
94920_NCI-H526_Small cell lung	1.6	94983_Caki-2_Clear cell renal	1.9
cancer/neuroendocrine_sscDNA		carcinoma_sscDNA
94921_NCI-N417_Small cell lung	1.4	94984_SW 839_Clear cell renal	1.5
cancer/neuroendocrine_sscDNA		carcinoma_sscDNA
94923_NCI-H82_Small cell lung	1.4	94986_G401_Wilms' tumor_sscDNA	4.0
cancer/neuroendocrine_sscDNA
94924_NCI-H157_Squamous cell lung	0.6	126768_293 cells_sscDNA	0.0
cancer (metastasis)_sscDNA
94925_NCI-H1155_Large cell lung	19.5	94987_Hs766T_Pancreatic	0.0
cancer/neuroendocrine_sscDNA		carcinoma (LN metastasis)_sscDNA
94926_NCI-H1299_Large cell lung	5.0	94988_CAPAN-1_Pancreatic	0.0
cancer/neuroendocrine_sscDNA		adenocarcinoma (liver
		metastasis)_sscDNA
94927_NCI-H727_Lung	39.0	94989_SU86.86_Pancreatic	4.5
carcinoid_sscDNA		carcinoma (liver
		metastasis)_sscDNA
94928_NCI-UMC-11_Lung	18.3	94990_BxPC-3_Pancreatic	0.0
carcinoid_sscDNA		adenocarcinoma_sscDNA
94929_LX-1_Small cell lung	0.0	94991_HPAC_Pancreatic	0.0
cancer_sscDNA		adenocarcinoma_sscDNA
94930_Colo-205_Colon cancer_sscDNA	0.0	94992_MIA PaCa-2_Pancreatic	0.0
		carcinoma_sscDNA
94931_KM12_Colon cancer_sscDNA	13.0	94993_CFPAC-1_Pancreatic ductal	11.4
		adenocarcinoma_sscDNA
94932_KM20L2_Colon cancer_sscDNA	0.0	94994_PANC-1_Pancreatic	0.0
		epithelioid ductal
		carcinoma_sscDNA
94933_NCI-H716_Colon	13.4	94996_T24_Bladder carcinma	0.0
cancer_sscDNA		(transitional cell)_sscDNA
94935_SW-48_Colon	0.0	94997_5637_Bladder	0.0
adenocarcinoma_sscDNA		carcinoma_sscDNA
94936_SW1116_Colon	0.0	94998_HT-1197_Bladder	0.0
adenocarcinoma_sscDNA		carcinoma_sscDNA
94937_LS 174T_Colon	0.0	94999_UM-UC-3_Bladder carcinma	0.0
adenocarcinoma_sscDNA		(transitional cell)_sscDNA
94938_SW-948_Colon	0.0	95000_A204_Rhabdomyosarcoma_sscDNA	2.4
adenocarcinoma_sscDNA
94939_SW-480_Colon	0.0	95001_HT-	0.0
adenocarcinoma_sscDNA		1080_Fibrosarcoma_sscDNA
94940_NCI-SNU-5_Gastric	0.0	95002_MG-63_Osteosarcoma	0.0
carcinoma_sscDNA		(bone)_sscDNA
112197_KATO III_Stomach_sscDNA	0.0	95003_SK-LMS-1_Leiomyosarcoma	4.6
		(vulva)_sscDNA
94943_NCI-SNU-16_Gastric	0.7	95004_SJRH30_Rhabdomyosarcoma	0.0
carcinoma_sscDNA		(met to bone marrow)_sscDNA
94944_NCI-SNU-1_Gastric	0.0	95005_A431_Epidermoid	0.0
carcinoma_sscDNA		carcinoma_sscDNA
94946_RF-1_Gastric	0.0	95007_WM266-	1.1
adenocarcinoma_sscDNA		4_Melanoma_sscDNA
94947_RF-48_Gastric	0.0	112195_DU 145_Prostate_sscDNA	4.4
adenocarcinoma_sscDNA
96778_MKN-45_Gastric	4.4	95012_MDA-MB-468_Breast	0.5
carcinoma_sscDNA		adenocarcinoma_sscDNA
94949_NCI-N87_Gastric	0.7	112196_SSC-4_Tongue_sscDNA	0.0
carcinoma_sscDNA
94951_OVCAR-5_Ovarian	0.0	112194_SSC-9_Tongue_sscDNA	0.0
carcinoma_sscDNA
94952_RL95-2_Uterine	1.4	112191_SSC-15_Tongue_sscDNA	0.0
carcinoma_sscDNA
94953_HelaS3_Cervical	0.0	95017_CAL 27_Squamous cell	0.0
adenocarcinoma_sscDNA		carcinoma of tongue_sscDNA

[0943]

TABLE AHE
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4412,		Ag4412,
Tissue Name	Run 190413471	Tissue Name	Run 190413471
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	3.9
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	4.0
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	11.4
		TNF alpha + IL-1beta
Primary Th2 rest	0.0	Small airway epithelium none	3.2
Primary Tr1 rest	0.0	Small airway epithelium	4.0
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	36.1	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	3.8
Secondary CD8	0.0	Astrocytes TNF alpha + IL-	4.9
lymphocyte rest		1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	6.6
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	5.1
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	25.9
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	20.9
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	100.0
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells	0.0	NCI-H292 IL-13	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	4.2	HPAEC TNF alpha + IL-1beta	6.3
Two Way MLR 7 day	0.0	Lung fibroblast none	5.7
PBMC rest	0.0	Lung fibroblast TNF alpha +	0.0
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	6.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070	0.0
		rest
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070	0.0
and IL-4		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	0.0
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	3.2
Macrophages rest	0.0	Lung	20.3
Macrophages LPS	4.9	Thymus	0.0
HUVEC none	0.0	Kidney	21.3
HUVEC starved	4.5

[0944]

TABLE AHF
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4412,		Ag4412,
Tissue Name	Run 264979086	Tissue Name	Run 264979086
Colon cancer 1	0.0	Bladder cancer NAT 2	0.0
Colon NAT 1	1.5	Bladder cancer NAT 3	0.0
Colon cancer 2	1.3	Bladder cancer NAT 4	0.0
Colon cancer NAT 2	0.0	Adenocarcinoma of the	6.5
		prostate 1
Colon cancer 3	1.8	Adenocarcinoma of the	0.6
		prostate 2
Colon cancer NAT 3	3.1	Adenocarcinoma of the	1.6
		prostate 3
Colon malignant	5.4	Adenocarcinoma of the	1.6
cancer 4		prostate 4
Colon normal adjacent	0.0	Prostate cancer NAT 5	0.5
tissue 4
Lung cancer 1	9.0	Adenocarcinoma of the	0.0
		prostate 6
Lung NAT 1	0.0	Adenocarcinoma of the	1.4
		prostate 7
Lung cancer 2	22.4	Adenocarcinoma of the	0.0
		prostate 8
Lung NAT 2	2.0	Adenocarcinoma of the	1.9
		prostate 9
Squamous cell	4.1	Prostate cancer NAT 10	0.0
carcinoma 3
Lung NAT 3	0.0	Kidney cancer 1	12.6
metastatic melanoma 1	4.7	KidneyNAT 1	4.8
Melanoma 2	0.0	Kidney cancer 2	100.0
Melanoma 3	0.0	Kidney NAT 2	5.3
metastatic melanoma 4	6.2	Kidney cancer 3	2.3
metastatic melanoma 5	5.7	Kidney NAT 3	1.2
Bladder cancer 1	0.0	Kidney cancer 4	14.5
Bladder cancer NAT 1	0.0	Kidney NAT 4	2.4
Bladder cancer 2	0.0

[0945] CNS_neurodegeneration_v1.0 Summary: Ag4412 This panel does not show differential expression of the CG110187-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of use of this gene in the central nervous system.

[0946] General_screening_panel_v1.4 Summary: Ag4412 Highest expression of the CG110187-01 gene is seen in the fetal brain (CT=29.8). This gene is also expressed at moderate to low levels in all CNS regions examined, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. The cadherins have been shown to be critical for CNS development, specifically for the guidance of axons, dendrites and/or growth cones in general. Therapeutic modulation of the levels of this protein, or possible signaling via this protein may be of utility in enhancing/directing compensatory synaptogenesis and fiber growth in the CNS in response to neuronal death (stroke, head trauma), axon lesion (spinal cord injury), or neurodegeneration (Alzheimer's, Parkinson's, Huntington's, vascular dementia or any neurodegenerative disease). Since protocadherins play an important role in synaptogenesis, this gene product may also be involved in depression, schizophrenia, which also involve synaptogeneisis. (Hilschmann N. Naturwissenschaften January 2001;88(1):2-12)

[0947] Moderate levels of expression are also seen in prostate, ovarian, lung and brain cancer cell lines. Thus, expression of this gene could be used to as a marker to detect the presence of these cancers. This gene encodes a protien that is homologous to cadherin which is involved in cellular adhesion. Dysregulation of cadherins has been observed in cancer, including renal cell carcinomas (Stassar, M J. Br J Cancer Nov. 2, 2000;85(9):1372-82). Therefore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of prostate, ovarian, lung and brain cancers.

[0948] Oncology_cell_line_screening_panel_v3.2 Summary: Ag4412 Significant expression of the CG110817-01 gene is restricted to lung cancer cell lines and the cerebellum, with highest expression in a small cell lung cancer cell line (CT=32.4). This expression is in agreement with expression in Panel 1.4, where significant levels of expression are detected in the brain and cancer cell lines. Thus, expression of this gene could be used as a marker for lung cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of lung cancer.

[0949] Panel 4.1D Summary: Ag4412 Significant expression of the CG110817-01 gene is restricted to untreated muco-epidermoid NCI-H292 cells (CT=34.9). Thus, the protein could be used to identify certain lung tumors similar to NCI-H292. This expression is in agreement with the previous panels, where significant levels of expression are detected in lung cancer cell lines. The encoded protein may also contribute to the normal function of the goblet cells within the lung. Therefore, designing therapeutics to this protein may be important for the treatment of emphysema and asthma as well as other lung diseases in which goblet cells or the mucus they produce have pathological consequences.

[0950] general oncology screening panel_v—2.4 Summary: Ag4412 Highest expression of the CG110817-01 gene is seen in kidney cancer (CT=32.2). In addition, significant levels of expression are also seen in kidney cancer and lung cancer when compared to expression in the normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of lung cancer.

[0951] AI. CG110205-01 and CG110205-02: A Disintegrin-Like and Metalloprotease (Reprolysin Type) with Thrombospondin

[0952] Expression of gene CG110205-01 and CG110205-02 was assessed using the primer-probe sets Ag2430, Ag4413, Ag6546, Ag6645, Ag7012 and Ag7058, described in Tables AIA, AIB, AIC, AID, AIE and AIF. Results of the RTQ-PCR runs are shown in Tables AIG, AIH, AII, AIJ, AIK, AIL, AIM, AIN and AIO. Please note that CG110205-02 is the peptide containing reprolysin and thrombospondin type 1 domains of CG110205-01 and only recognized by probes Ag2430, and Ag4413.

TABLE AIA
Probe Name Ag2430
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cattggaaagaatggcaaga-3′	20	1209	270
Probe	TET-5′-catgatcatgccatcttactaacagga-3′-TAMRA	27	1231	271
Reverse	5′-tcacatggttcattcttccaa-3′	21	1272	272

[0953]

TABLE AIB
Probe Name Ag4413
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ttggaagaatgaaccatgtga-3′	21	1272	273
Probe	TET-5′-ccccatcagtggaatgtgctctaagt-3′-TAMRA	26	1308	274
Reverse	5′-caagtcctgtgtcctcattgat-3′	22	1348	275

[0954]

TABLE AIC
Probe Name Ag6546
			Start	SEQ ID
Primers	Sequences	Length	Position	No.
Forward	5′-ggatagcttggaagtatgcactt-3′	23	2633	276
Probe	TET-5′-caaggtcatgaatggaactccaccag-3′-TAMRA	26	2658	277
Reverse	5′-ctggcatccagcaggtatag-3′	20	2700	278

[0955]

TABLE AID
Probe Name Ag6645
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggatagcttggaagtatgcactt-3′	23	2633	279
Probe	TET-5′-caaggtcatgaatggaactccaccag-3′-TAMRA	26	2658	280
Reverse	5′-ctggcatccagcaggtatag-3′	20	2700	281

[0956]

TABLE AIE
Probe Name Ag7012
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ctgccctccacaatgga-3′	17	2877	282
Probe	TET-5′-ccttggaccctggtctcagtgttcca-3′-TAMRA	26	2895	283
Reverse	5′-cagaggagttcacgcttcct-3′	20	2941	284

[0957]

TABLE AIF
Probe Name Ag7058
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-caagttgtctgctccatcagaa-3′	22	3380	285
Probe	TET-5′-ccggtgctacgagcctgtaatacaaacttc-3′-TAMRA	30	3406	286
Reverse	5′-gatcctctctcttttcaggagct-3′	23	3441	287

[0958]

TABLE AIG
AI_comprehensive panel_v1.0
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag4413, Run	Ag4413, Run		Ag4413, Run	Ag4413, Run
Tissue Name	248080021	251506632	Tissue Name	248080021	251506632
110967 COPD-F	0.3	5.1	112427 Match	0.8	1.4
			Control Psoriasis-F
110980 COPD-F	0.2	0.0	112418 Psoriasis-M	0.5	3.3
110968 COPD-M	0.5	4.2	112723 Match	2.3	22.8
			Control Psoriasis-M
110977 COPD-M	0.2	0.5	112419 Psoriasis-M	0.4	0.7
110989	0.5	33.2	112424 Match	0.3	6.4
Emphysema-F			Control Psoriasis-M
110992	0.7	3.5	112420 Psoriasis-M	1.2	7.3
Emphysema-F
110993	0.4	7.9	112425 Match	0.2	10.8
Emphysema-F			Control Psoriasis-M
110994	0.2	3.4	104689 (MF) OA	7.5	17.1
Emphysema-F			Bone-Backus
110995	0.7	4.0	104690 (MF) Adj	0.3	1.5
Emphysema-F			“Normal” Bone-
			Backus
110996	0.3	0.9	104691 (MF) OA	0.2	3.6
Emphysema-F			Synovium-
			Backus
110997 Asthma-M	0.3	3.0	104692 (BA) OA	0.0	0.0
			Cartilage-Backus
111001 Asthma-F	0.1	24.1	104694 (BA) OA	23.7	3.9
			Bone-Backus
111002 Asthma-F	0.3	22.4	104695 (BA) Adj	2.6	6.3
			“Normal” Bone-
			Backus
111003 Atopic	0.9	71.2	104696 (BA) OA	1.0	16.6
Asthma-F			Synovium-
			Backus
111004 Atopic	1.7	33.4	104700 (SS) OA	2.2	2.3
Asthma-F			Bone-Backus
111005 Atopic	1.6	38.2	104701 (SS) Adj	5.9	4.1
Asthma-F			“Normal” Bone-
			Backus
111006 Atopic	0.4	7.9	104702 (SS) OA	1.1	60.3
Asthma-F			Synovium-
			Backus
111417 Allergy-M	0.5	1.1	117093 OA	0.2	3.2
			Cartilage Rep7
112347 Allergy-M	0.8	0.0	112672 OA	0.1	0.6
			Bone5
112349 Normal	0.8	0.0	112673 OA	0.1	0.0
Lung-F			Synovium5
112357 Normal	0.7	17.6	112674 OA	0.1	0.6
Lung-F			Synovial Fluid
			cells5
112354 Normal	0.2	0.7	117100 OA	0.1	0.5
Lung-M			Cartilage Rep14
112374 Crohns-F	1.4	6.3	112756 OA	1.0	20.7
			Bone9
112389 Match	0.5	0.0	112757 OA	0.0	0.0
Control Crohns-F			Synovium9
112375 Crohns-F	1.8	5.1	112758 OA	0.5	12.9
			Synovial Fluid
			Cells9
112732 Match	0.0	0.0	117125 RA	0.5	24.3
Control Crohns-F			Cartilage Rep2
112725 Crohns-M	0.4	0.0	113492 Bone2	0.0	1.4
			RA
112387 Match	0.2	0.6	113493	0.0	0.0
Control Crohns-M			Synovium2 RA
112378 Crohns-M	0.6	0.0	113494 Syn Fluid	0.0	1.0
			Cells RA
112390 Match	0.2	6.0	113499	0.0	0.0
Control Crohns-M			Cartilage4 RA
112726 Crohns-M	1.9	100.0	113500 Bone4	0.0	0.0
			RA
112731 Match	0.4	52.1	113501	0.0	0.7
Control Crohns-M			Synovium4 RA
112380 Ulcer	0.6	29.3	113502 Syn Fluid	0.0	1.5
Col-F			Cells4 RA
112734 Match	100.0	0.6	113495	0.0	0.8
Control Ulcer			Cartilage3 RA
Col-F
112384 Ulcer	1.4	4.2	113496 Bone3	0.0	0.5
Col-F			RA
112737 Match	1.2	52.1	113497	0.0	0.6
Control Ulcer			Synovium3 RA
Col-F
112386 Ulcer	0.1	0.7	113498 Syn Fluid	0.0	0.0
Col-F			Cells3 RA
112738 Match	0.1	0.0	117106 Normal	0.1	1.3
Control Ulcer			Cartilage Rep20
Col-F
112381 Ulcer	0.3	0.5	113663 Bone3	0.7	0.1
Col-M			Normal
112735 Match	1.9	0.9	113664	0.1	0.0
Control Ulcer			Synovium3
Col-M			Normal
112382 Ulcer	0.4	0.0	113665 Syn Fluid	0.4	0.0
Col-M			Cells3 Normal
112394 Match	0.1	0.6	117107 Normal	0.0	1.3
Control Ulcer			Cartilage Rep22
Col-M
112383 Ulcer	1.8	18.7	113667 Bone4	0.2	0.9
Col-M			Normal
112736 Match	1.6	0.0	113668	0.1	1.6
Control Ulcer			Synovium4
Col-M			Normal
112423 Psoriasis-F	1.0	11.2	113669 Syn Fluid	0.2	1.9
			Cells4 Normal

[0959]

TABLE AIH
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag2430, Run	Ag4413, Run		Ag2430, Run	Ag4413, Run
Tissue Name	208712834	224505949	Tissue Name	208712834	224505949
AD 1 Hippo	0.0	0.0	Control (Path)	2.2	3.0
			3 Temporal
			Ctx
AD 2 Hippo	15.4	21.6	Control (Path)	1.1	4.0
			4 Temporal
			Ctx
AD 3 Hippo	0.0	0.8	AD 1 Occipital	0.7	0.0
			Ctx
AD 4 Hippo	17.6	27.5	AD 2 Occipital	0.0	0.0
			Ctx (Missing)
AD 5 Hippo	13.9	22.5	AD 3 Occipital	0.0	0.0
			Ctx
AD 6 Hippo	43.2	0.0	AD 4 Occipital	52.5	94.0
			Ctx
Control 2	62.9	85.9	AD 5 Occipital	27.7	25.5
Hippo			Ctx
Control 4	0.0	1.6	AD 6 Occipital	24.0	27.7
Hippo			Ctx
Control (Path)	3.2	14.5	Control 1	0.0	0.0
3 Hippo			Occipital Ctx
AD 1	0.9	0.7	Control 2	52.1	66.0
Temporal Ctx			Occipital Ctx
AD 2	21.9	37.6	Control 3	3.1	11.1
Temporal Ctx			Occipital Ctx
AD 3	0.0	0.0	Control 4	0.0	0.0
Temporal Ctx			Occipital Ctx
AD 4	57.0	97.9	Control (Path)	59.9	73.2
Temporal Ctx			1 Occipital Ctx
AD 5 Inf	69.7	65.1	Control (Path)	6.6	10.1
Temporal Ctx			2 Occipital Ctx
AD 5 Sup	38.2	26.2	Control (Path)	5.4	4.7
Temporal Ctx			3 Occipital Ctx
AD 6 Inf	100.0	100.0	Control (Path)	0.0	0.0
Temporal Ctx			4 Occipital Ctx
AD 6 Sup	36.6	37.6	Control 1	0.0	0.0
Temporal Ctx			Parietal Ctx
Control 1	0.0	0.8	Control 2	37.6	38.4
Temporal Ctx			Parietal Ctx
Control 2	36.6	45.7	Control 3	6.3	6.6
Temporal Ctx			Parietal Ctx
Control 3	9.3	12.5	Control (Path)	19.5	26.1
Temporal Ctx			1 Parietal Ctx
Control 3	0.0	1.4	Control (Path)	7.2	9.1
Temporal Ctx			2 Parietal Ctx
Control (Path)	18.0	28.1	Control (Path)	0.0	4.6
1 Temporal			3 Parietal Ctx
Ctx
Control (Path)	5.1	0.0	Control (Path)	0.0	0.9
2 Temporal			4 Parietal Ctx
Ctx

[0960]

TABLE AII
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4413,		Ag4413,
Tissue Name	Run 219923153	Tissue Name	Run 219923153
Adipose	7.2	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	0.2
Hs688(A).T
Melanoma*	0.0	Gastric ca. (liver met.)	0.0
Hs688(B).T		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.5
Melanoma* LOXIMVI	37.4	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell	0.0	Colon ca.* (SW480 met)	49.0
carcinoma SCC-4		SW620
Testis Pool	1.8	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	0.0
PC-3
Prostate Pool	1.3	Colon ca. CaCo-2	3.0
Placenta	19.5	Colon cancer tissue	2.6
Uterus Pool	0.9	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.2	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	11.2
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	1.7
Ovarian ca. IGROV-1	0.1	Stomach Pool	6.3
Ovarian ca. OVCAR-8	3.0	Bone Marrow Pool	2.7
Ovary	19.2	Fetal Heart	0.3
Breast ca. MCF-7	0.0	Heart Pool	1.5
Breast ca. MDA-MB-	0.0	Lymph Node Pool	20.3
231
Breast ca. BT 549	1.1	Fetal Skeletal Muscle	3.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	11.7	Thymus Pool	8.4
Trachea	0.9	CNS cancer (glio/astro)	39.0
		U87-MG
Lung	0.6	CNS cancer (glio/astro) U-	1.8
		118-MG
Fetal Lung	0.6	CNS cancer (neuro; met)	0.2
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	9.7	CNS cancer (astro) SNB-	0.7
		75
Lung ca. NCI-H146	3.1	CNS cancer (glio) SNB-19	0.2
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	1.3
Lung ca. A549	0.0	Brain (Amygdala) Pool	4.0
Lung ca. NCI-H526	5.4	Brain (cerebellum)	100.0
Lung ca. NCI-H23	0.9	Brain (fetal)	2.7
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	2.0
Lung ca. HOP-62	0.4	Cerebral Cortex Pool	4.3
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	5.5
		Pool
Liver	0.0	Brain (Thalamus) Pool	8.7
Fetal Liver	0.7	Brain (whole)	11.8
Liver ca. HepG2	0.2	Spinal Cord Pool	8.0
Kidney Pool	2.1	Adrenal Gland	0.0
Fetal Kidney	17.1	Pituitary gland Pool	3.2
Renal ca. 786-0	0.0	Salivary Gland	6.8
Renal ca. A498	0.0	Thyroid (female)	0.3
Renal ca. ACHN	3.1	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	30.1	Pancreas Pool	8.2

[0961]

TABLE AIJ
Oncology_cell_line_screening_panel_v3.2
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag2430, Run		Ag2430, Run
Tissue Name	258381230	Tissue Name	258381230
94905_Daoy_Medulloblastoma/Cerebellum—	0.0	94954_Ca Ski_Cervical	0.0
sscDNA		epidermoid carcinoma
		(metastasis)_sscDNA
94906_TE671_Medulloblastom/Cerebellum—	0.0	94955_ES-2_Ovarian clear cell	0.0
sscDNA		carcinoma_sscDNA
94907_D283	0.0	94957_Ramos/6 h stim—	0.0
Med_Medulloblastoma/Cerebellum—		Stimulated with PMA/ionomycin
sscDNA		6 h_sscDNA
94908_PFSK-1_Primitive	0.0	94958_Ramos/14 h stim—	0.0
Neuroectodermal/Cerebellum_sscDNA		Stimulated with PMA/ionomycin
		14 h_sscDNA
94909_XF-498_CNS_sscDNA	0.0	94962_MEG-01_Chronic	0.0
		myelogenous leukemia
		(megokaryoblast)_sscDNA
94910_SNB-	0.0	94963_Raji_Burkitt's	0.0
78_CNS/glioma_sscDNA		lymphoma_sscDNA
94911_SF-	0.0	94964_Daudi_Burkitt's	0.0
268_CNS/glioblastoma_sscDNA		lymphoma_sscDNA
94912_T98G_Glioblastoma_sscDNA	0.0	94965_U266_B-cell	0.0
		plasmacytoma/myeloma_sscDNA
96776_SK-N-SH_Neuroblastoma	0.0	94968_CA46_Burkitt's	0.0
(metastasis)_sscDNA		lymphoma_sscDNA
94913_SF-	0.0	94970_RL_non-Hodgkin's B-cell	0.0
295_CNS/glioblastoma_sscDNA		lymphoma_sscDNA
132565_NT2 pool_sscDNA	0.1	94972_JM1_pre-B-cell	0.0
		lymphoma/leukemia_sscDNA
94914_Cerebellum_sscDNA	57.8	94973_Jurkat_T cell	0.0
		leukemia_sscDNA
96777_Cerebellum_sscDNA	25.5	94974_TF-	0.0
		1_Erythroleukemia_sscDNA
94916_NCI-	0.0	94975_HUT 78_T-cell	0.0
H292_Mucoepidermoid lung		lymphoma_sscDNA
carcinoma_sscDNA
94917_DMS-114_Small cell lung	17.9	94977_U937_Histiocytic	0.0
cancer_sscDNA		lymphoma_sscDNA
94918_DMS-79_Small cell lung	100.0	94980_KU-812_Myelogenous	0.0
cancer/neuroendocrine_sscDNA		leukemia_sscDNA
94919_NCI-H146_Small cell lung	2.9	94981_769-P_Clear cell renal	0.0
cancer/neuroendocrine_sscDNA		carcinoma_sscDNA
94920_NCI-H526_Small cell lung	10.9	94983_Caki-2_Clear cell renal	0.0
cancer/neuroendocrine_sscDNA		carcinoma_sscDNA
94921_NCI-N417_Small cell lung	0.0	94984_SW 839_Clear cell renal	0.0
cancer/neuroendocrine_sscDNA		carcinoma_sscDNA
94923_NCI-H82_Small cell lung	0.0	94986_G401_Wilms'	0.0
cancer/neuroendocrine_sscDNA		tumor_sscDNA
94924_NCI-H157_Squamous cell	0.0	126768_293 cells_sscDNA	0.0
lung cancer (metastasis)_sscDNA
94925_NCI-H1155_Large cell	0.0	94987_Hs766T_Pancreatic	0.0
lung		carcinoma (LN
cancer/neuroendocrine_sscDNA		metastasis)_sscDNA
94926_NCI-H1299_Large cell	0.0	94988_CAPAN-1_Pancreatic	0.0
lung		adenocarcinoma (liver
cancer/neuroendocrine_sscDNA		metastasis)_sscDNA
94927_NCI-H727_Lung	0.3	94989_SU86.86_Pancreatic	0.0
carcinoid_sscDNA		carcinoma (liver
		metastasis)_sscDNA
94928_NCI-UMC-11_Lung	0.0	94990_BxPC-3_Pancreatic	0.0
carcinoid_sscDNA		adenocarcinoma_sscDNA
94929_LX-1_Small cell lung	3.8	94991_HPAC_Pancreatic	0.0
cancer_sscDNA		adenocarcinoma_sscDNA
94930_Colo-205_Colon	0.0	94992_MIA PaCa-2_Pancreatic	0.0
cancer_sscDNA		carcinoma_sscDNA
94931_KM12_Colon	0.0	94993_CFPAC-1_Pancreatic	0.0
cancer_sscDNA		ductal adenocarcinoma_sscDNA
94932_KM20L2_Colon	0.0	94994_PANC-1_Pancreatic	0.0
cancer_sscDNA		epithelioid ductal
		carcinoma_sscDNA
94933_NCI-H716_Colon	0.0	94996_T24_Bladder carcinma	0.0
cancer_sscDNA		(transitional cell)_sscDNA
94935_SW-48_Colon	0.0	94997_5637_Bladder	0.0
adenocarcinoma_sscDNA		carcinoma_sscDNA
94936_SW1116_Colon	0.0	94998_HT-1197_Bladder	0.0
adenocarcinoma_sscDNA		carcinoma_sscDNA
94937_LS 174T_Colon	0.0	94999_UM-UC-3_Bladder	0.0
adenocarcinoma_sscDNA		carcinma (transitional
		cell)_sscDNA
94938_SW-948_Colon	0.0	95000_A204_Rhabdomyosarcoma—	0.4
adenocarcinoma_sscDNA		sscDNA
94939_SW-480_Colon	0.0	95001_HT-	0.2
adenocarcinoma_sscDNA		1080_Fibrosarcoma_sscDNA
94940_NCI-SNU-5_Gastric	0.0	95002_MG-63_Osteosarcoma	0.0
carcinoma_sscDNA		(bone)_sscDNA
112197_KATO	0.0	95003_SK-LMS-	0.0
III_Stomach_sscDNA		1_Leiomyosarcoma
		(vulva)_sscDNA
94943_NCI-SNU-16_Gastric	0.0	95004_SJRH30_Rhabdomyosarcoma	0.0
carcinoma_sscDNA		(met to bone
		marrow)_sscDNA
94944_NCI-SNU-1_Gastric	0.0	95005_A431_Epidermoid	0.0
carcinoma_sscDNA		carcinoma_sscDNA
94946_RF-1_Gastric	0.0	95007_WM266-	0.0
adenocarcinoma_sscDNA		4_Melanoma_sscDNA
94947_RF-48_Gastric	0.0	112195_DU	0.0
adenocarcinoma_sscDNA		145_Prostate_sscDNA
96778_MKN-45_Gastric	0.0	95012_MDA-MB-468_Breast	0.0
carcinoma_sscDNA		adenocarcinoma_sscDNA
94949_NCI-N87_Gastric	0.0	112196_SSC-4_Tongue_sscDNA	0.0
carcinoma_sscDNA
94951_OVCAR-5_Ovarian	0.0	112194_SSC-9_Tongue_sscDNA	0.0
carcinoma_sscDNA
94952_RL95-2_Uterine	0.0	112191_SSC-15_Tongue_sscDNA	0.0
carcinoma_sscDNA
94953_HelaS3_Cervical	0.0	95017_CAL 27_Squamous cell	0.0
adenocarcinoma_sscDNA		carcinoma of tongue_sscDNA

[0962]

TABLE AIK
Panel 1.3D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag2430,		Ag2430,
Tissue Name	Run 159505456	Tissue Name	Run 159505456
Liver adenocarcinoma	0.0	Kidney (fetal)	9.3
Pancreas	0.0	Renal ca. 786-0	0.0
Pancreatic ca. CAPAN 2	0.0	Renal ca. A498	0.5
Adrenal gland	1.1	Renal ca. RXF 393	0.0
Thyroid	0.2	Renal ca. ACHN	3.8
Salivary gland	15.0	Renal ca. UO-31	13.9
Pituitary gland	13.2	Renal ca. TK-10	0.0
Brain (fetal)	0.3	Liver	0.0
Brain (whole)	40.9	Liver (fetal)	0.0
Brain (amygdala)	9.7	Liver ca. (hepatoblast)	0.0
		HepG2
Brain (cerebellum)	100.0	Lung	0.0
Brain (hippocampus)	37.9	Lung (fetal)	2.6
Brain (substantia nigra)	8.0	Lung ca. (small cell)	9.9
		LX-1
Brain (thalamus)	12.2	Lung ca. (small cell)	29.5
		NCI-H69
Cerebral Cortex	4.1	Lung ca. (s. cell var.)	0.0
		SHP-77
Spinal cord	6.4	Lung ca. (large	0.0
		cell)NCI-H460
glio/astro U87-MG	59.9	Lung ca. (non-sm. cell)	0.0
		A549
glio/astro U-118-MG	6.7	Lung ca. (non-s. cell)	2.0
		NCI-H23
astrocytoma SW1783	0.0	Lung ca. (non-s. cell)	0.0
		HOP-62
neuro*; met SK-N-AS	0.0	Lung ca. (non-s. cl) NCI-	0.0
		H522
astrocytoma SF-539	0.0	Lung ca. (squam.) SW	0.0
		900
astrocytoma SNB-75	0.6	Lung ca. (squam.) NCI-	0.8
		H596
glioma SNB-19	0.3	Mammary gland	30.8
glioma U251	17.8	Breast ca.* (pl. ef) MCF-7	0.0
glioma SF-295	0.5	Breast ca.* (pl. ef)	0.0
		MDA-MB-231
Heart (fetal)	0.0	Breast ca.* (pl. ef) T47D	0.0
Heart	0.0	Breast ca. BT-549	31.9
Skeletal muscle (fetal)	13.5	Breast ca. MDA-N	0.3
Skeletal muscle	0.0	Ovary	32.8
Bone marrow	0.0	Ovarian ca. OVCAR-3	0.0
Thymus	3.1	Ovarian ca. OVCAR-4	0.0
Spleen	0.0	Ovarian ca. OVCAR-5	0.0
Lymph node	0.6	Ovarian ca. OVCAR-8	0.0
Colorectal	0.9	Ovarian ca. IGROV-1	0.2
Stomach	0.0	Ovarian ca.* (ascites)	0.0
		SK-OV-3
Small intestine	0.3	Uterus	3.0
Colon ca. SW480	0.0	Placenta	47.0
Colon ca.*	75.3	Prostate	1.4
SW620(SW480 met)
Colon ca. HT29	0.0	Prostate ca.* (bone	0.0
		met)PC-3
Colon ca. HCT-116	0.0	Testis	1.2
Colon ca. CaCo-2	2.8	Melanoma Hs688(A).T	0.0
Colon ca.	5.1	Melanoma* (met)	0.0
tissue(ODO3866)		Hs688(B).T
Colon ca. HCC-2998	0.0	Melanoma UACC-62	0.0
Gastric ca.* (liver met)	0.0	Melanoma M14	0.0
NCI-N87
Bladder	1.7	Melanoma LOX IMVI	45.4
Trachea	2.2	Melanoma* (met) SK-	0.0
		MEL-5
Kidney	0.2	Adipose	18.6

[0963]

TABLE AIL
Panel 2D
	Rel. Exp. (%) Ag2430,		Rel. Exp. (%) Ag2430,
Tissue Name	Run 159505825	Tissue Name	Run 159505825
Normal Colon	15.4	Kidney Margin 8120608	0.6
CC Well to Mod Diff	12.9	Kidney Cancer 8120613	5.1
(ODO3866)
CC Margin (ODO3866)	0.0	Kidney Margin 8120614	6.1
CC Gr.2 rectosigmoid	0.3	Kidney Cancer 9010320	9.7
(ODO3868)
CC Margin (ODO3868)	3.0	Kidney Margin 9010321	2.7
CC Mod Diff (ODO3920)	5.3	Normal Uterus	23.8
CC Margin (ODO3920)	2.3	Uterus Cancer 064011	25.5
CC Gr.2 ascend colon	12.7	Normal Thyroid	2.9
(ODO3921)
CC Margin (ODO3921)	4.6	Thyroid Cancer 064010	23.8
CC from Partial Hepatectomy	0.0	Thyroid Cancer A302152	14.3
(ODO4309) Mets
Liver Margin (ODO4309)	0.0	Thyroid Margin A302153	5.6
Colon mets to lung	0.0	Normal Breast	58.6
(OD04451-01)
Lung Margin (OD04451-02)	0.0	Breast Cancer (OD04566)	2.3
Normal Prostate 6546-1	1.0	Breast Cancer (OD04590-	30.6
		01)
Prostate Cancer (OD04410)	1.2	Breast Cancer Mets	17.0
		(OD04590-03)
Prostate Margin (OD04410)	47.0	Breast Cancer Metastasis	6.6
		(OD04655-05)
Prostate Cancer (OD04720-	7.9	Breast Cancer 064006	7.1
01)
Prostate Margin (OD04720-	0.0	Breast Cancer 1024	59.0
02)
Normal Lung 061010	11.4	Breast Cancer 9100266	33.0
Lung Met to Muscle	1.2	Breast Margin 9100265	26.6
(ODO4286)
Muscle Margin (ODO4286)	6.8	Breast Cancer A209073	43.8
Lung Malignant Cancer	10.9	Breast Margin A209073	68.3
(OD03126)
Lung Margin (OD03126)	2.5	Normal Liver	0.0
Lung Cancer (OD04404)	2.3	Liver Cancer 064003	0.8
Lung Margin (OD04404)	24.7	Liver Cancer 1025	0.0
Lung Cancer (OD04565)	6.9	Liver Cancer 1026	3.0
Lung Margin (OD04565)	1.2	Liver Cancer 6004-T	0.0
Lung Cancer (OD04237-01)	100.0	Liver Tissue 6004-N	2.9
Lung Margin (OD04237-02)	9.8	Liver Cancer 6005-T	0.0
Ocular Mel Met to Liver	0.0	Liver Tissue 6005-N	0.0
(ODO4310)
Liver Margin (ODO4310)	0.0	Normal Bladder	4.8
Melanoma Mets to Lung	1.5	Bladder Cancer 1023	2.5
(OD04321)
Lung Margin (OD04321)	0.0	Bladder Cancer A302173	16.3
Normal Kidney	24.7	Bladder Cancer	6.1
		(OD04718-01)
Kidney Ca, Nuclear grade 2	6.4	Bladder Normal Adjacent	53.2
(OD04338)		(OD04718-03)
Kidney Margin (OD04338)	10.5	Normal Ovary	18.2
Kidney Ca Nuclear grade 1/2	5.5	Ovarian Cancer 064008	30.1
(OD04339)
Kidney Margin (OD04339)	3.8	Ovarian Cancer	2.7
		(OD04768-07)
Kidney Ca, Clear cell type	14.1	Ovary Margin	6.6
(OD04340)		(OD04768-08)
Kidney Margin (OD04340)	3.1	Normal Stomach	0.8
Kidney Ca, Nuclear grade 3	2.0	Gastric Cancer 9060358	3.9
(OD04348)
Kidney Margin (OD04348)	5.0	Stomach Margin 9060359	0.0
Kidney Cancer (OD04622-01)	1.0	Gastric Cancer 9060395	8.0
Kidney Margin (OD04622-	0.0	Stomach Margin 9060394	1.8
03)
Kidney Cancer (OD04450-01)	6.5	Gastric Cancer 9060397	12.2
Kidney Margin (OD04450-	11.3	Stomach Margin 9060396	0.0
03)
Kidney Cancer 8120607	2.6	Gastric Cancer 064005	10.7

[0964]

TABLE AIM
Panel 4.1D
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)	Exp. (%)
	Ag4413,	Ag4413,	Ag7012,		Ag4413,	Ag4413,	Ag7012,
	Run	Run	Run		Run	Run	Run
Tissue Name	190281896	249495488	279065633	Tissue Name	190281896	249495488	279065633
Secondary Th1 act	0.0	0.0	0.0	HUVEC IL-	16.6	12.1	24.7
				1beta
Secondary Th2 act	0.4	0.0	0.0	HUVEC IFN	52.9	53.2	57.8
				gamma
Secondary Tr1 act	0.6	0.0	0.0	HUVEC TNF	5.0	0.0	4.2
				alpha + IFN
				gamma
Secondary Th1	1.1	0.0	0.0	HUVEC TNF	6.4	0.0	0.9
rest				alpha + IL4
Secondary Th2	0.0	0.0	0.0	HUVEC IL-11	49.3	54.0	79.0
rest
Secondary Tr1	0.0	0.0	0.0	Lung	33.0	25.0	66.0
rest				Microvascular
				EC none
Primary Th1 act	0.0	0.0	0.0	Lung	42.9	8.7	17.2
				Microvascular
				EC TNF alpha +
				IL-1beta
Primary Th2 act	0.0	0.0	0.0	Microvascular	15.7	0.4	4.8
				Dermal EC none
Primary Tr1 act	0.0	0.0	0.0	Microsvasular	5.5	3.0	4.2
				Dermal EC
				TNF alpha + IL-
				1beta
Primary Th1 rest	0.0	0.0	0.0	Bronchial	0.0	0.0	0.0
				epithelium
				TNF alpha +
				IL1beta
Primary Th2 rest	0.0	0.0	0.0	Small airway	0.0	0.0	0.0
				epithelium none
Primary Tr1 rest	0.0	0.0	0.0	Small airway	0.0	0.0	0.0
				epithelium
				TNF alpha + IL-
				1beta
CD45RA CD4	0.0	0.0	0.0	Coronery artery	3.6	2.8	0.5
lymphocyte act				SMC rest
CD45RO CD4	0.0	0.0	0.0	Coronery artery	1.9	2.8	1.0
lymphocyte act				SMC TNF alpha +
				IL-1beta
CD8 lymphocyte	0.0	0.0	0.0	Astrocytes rest	0.0	0.9	0.0
act
Secondary CD8	0.0	0.0	0.0	Astrocytes	0.0	0.0	0.0
lymphocyte rest				TNF alpha + IL-
				1beta
Secondary CD8	0.0	0.0	0.0	KU-812	5.8	0.0	0.0
lymphocyte act				(Basophil) rest
CD4 lymphocyte	0.0	0.0	0.0	KU-812	0.9	0.0	0.0
none				(Basophil)
				PMA/ionomycin
2ry	0.0	0.0	0.0	CCD1106	0.0	0.0	0.0
Th1/Th2/Tr1_anti-				(Keratinocytes)
CD95 CH11				none
LAK cells rest	0.0	0.0	0.0	CCD1106	0.0	0.0	0.0
				(Keratinocytes)
				TNF alpha + IL-
				1beta
LAK cells IL-2	0.0	0.0	0.0	Liver cirrhosis	0.4	0.0	0.0
LAX cells IL-	0.0	0.0	0.0	NCI-H292 none	0.0	0.0	0.0
2 + IL-12
LAK cells IL-	0.0	0.0	0.0	NCI-H292 IL-4	0.0	0.0	0.0
2 + IFN gamma
LAK cells IL-2 +	0.0	0.0	0.0	NCI-H292 IL-9	0.0	0.0	0.0
IL-18
LAK cells	0.0	0.0	0.0	NCI-H292 IL-13	0.0	0.0	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	0.0	0.0	NCI-H292 IFN	0.0	0.0	0.0
				gamma
Two Way MLR 3	0.0	0.0	0.0	HPAEC none	71.2	25.7	35.1
day
Two Way MLR 5	2.2	0.0	0.0	HPAEC TNF	100.0	100.0	100.0
day				alpha + IL-1
				beta
Two Way MLR 7	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.0
day				none
PBMC rest	0.0	0.0	0.0	Lung fibroblast	0.3	0.0	0.0
				TNF alpha + IL-
				1beta
PBMC PWM	0.0	0.0	0.0	Lung fibroblast	0.3	0.0	0.0
				IL-4
PBMC PHA-L	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.0
				IL-9
Ramos (B cell)	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.0
none				IL-13
Ramos (B cell)	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.0
ionomycin				IFN gamma
B lymphocytes	0.0	0.0	0.0	Dermal	0.0	0.0	0.0
PWM				fibroblast
				CCD1070 rest
B lymphocytes	0.0	0.0	0.0	Dermal	0.0	0.0	0.0
CD40L and IL-4				fibroblast
				CCD1070 TNF
				alpha
EOL-1 dbcAMP	0.0	0.0	0.0	Dermal	0.0	0.0	0.0
				fibroblast
				CCD1070 IL-1
				beta
EOL-1 dbcAMP	0.0	0.0	0.0	Dermal	0.0	0.0	0.0
PMA/ionomycin				fibroblast IFN
				gamma
Dendritic cells	0.0	0.0	0.0	Dermal	0.0	0.0	0.0
none				fibroblast IL-4
Dendritic cells	5.8	0.0	0.0	Dermal	0.4	0.0	0.0
LPS				Fibroblasts rest
Dendritic cells	0.0	0.0	0.0	Neutrophils	0.0	0.0	0.0
anti-CD40				TNFa + LPS
Monocytes rest	0.0	0.0	0.0	Neutrophils rest	0.0	0.0	0.0
Monocytes LPS	0.0	0.0	0.0	Colon	0.0	0.0	0.0
Macrophages rest	0.0	0.0	0.0	Lung	5.7	0.0	0.0
Macrophages LPS	0.0	0.0	0.0	Thymus	2.7	0.3	1.6
HUVEC none	33.4	14.9	27.5	Kidney	0.0	0.8	1.0
HUVEC starved	55.9	20.6	49.7

[0965]

TABLE AIN
Panel 4D
	Rel. Exp. (%) Ag2430,		Rel. Exp. (%) Ag2430,
Tissue Name	Run 159506306	Tissue Name	Run 159506306
Secondary Th1 act	0.0	HUVEC IL-1beta	5.9
Secondary Th2 act	0.6	HUVEC IFN gamma	40.3
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	5.1
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	4.0
Secondary Th2 rest	0.0	HUVEC IL-11	47.3
Secondary Tr1 rest	0.0	Lung Microvascular EC none	22.1
Primary Th1 act	0.0	Lung Microvascular EC	22.5
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	20.4
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	3.8
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	4.2
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	2.1
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	1.1
Secondary CD8	0.0	Astrocytes TNF alpha + IL-	0.9
lymphocyte rest		1beta
Secondary CD8	0.0	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	0.4
LAK cells IL-2 + IL-12	0.0	Lupus kidney	0.2
LAK cells IL-2 + IFN	0.0	NCI-H292 none	0.0
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-4	0.0
LAK cells	0.0	NCI-H292 IL-9	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IL-13	0.0
Two Way MLR 3 day	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 5 day	0.0	HPAEC none	85.3
Two Way MLR 7 day	0.0	HPAEC TNF alpha + IL-1beta	56.6
PBMC rest	0.0	Lung fibroblast none	0.0
PBMC PWM	0.0	Lung fibroblast TNF alpha +	0.0
		IL-1beta
PBMC PHA-L	0.0	Lung fibroblast IL-4	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IL-13	0.0
B lymphocytes PWM	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070	0.0
and IL-4		rest
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	0.0
		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	0.0
PMA/ionomycin		IL-1beta
Dendritic cells none	0.0	Dermal fibroblast IFN gamma	0.0
Dendritic cells LPS	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells anti-CD40	0.0	IBD Colitis 2	0.0
Monocytes rest	0.0	IBD Crohn's	0.0
Monocytes LPS	0.0	Colon	0.7
Macrophages rest	0.0	Lung	3.1
Macrophages LPS	0.0	Thymus	2.6
HUVEC none	38.7	Kidney	7.2
HUVEC starved	100.0

[0966]

TABLE AIO
Panel CNS_1
	Rel. Exp. (%) Ag2430, Run		Rel. Exp. (%) Ag2430, Run
Tissue Name	171656292	Tissue Name	171656292
BA4 Control	0.0	BA17 PSP	2.9
BA4 Control2	19.6	BA17 PSP2	0.0
BA4 Alzheimer's2	0.0	Sub Nigra Control	94.0
BA4 Parkinson's	0.0	Sub Nigra Control2	25.9
BA4 Parkinson's2	17.0	Sub Nigra Alzheimer's2	15.7
BA4 Huntington's	9.8	Sub Nigra Parkinson's2	36.6
BA4	0.0	Sub Nigra Huntington's	100.0
Huntington's2
BA4 PSP	0.0	Sub Nigra	2.8
		Huntington's2
BA4 PSP2	11.0	Sub Nigra PSP2	29.1
BA4 Depression	19.5	Sub Nigra Depression	62.4
BA4 Depression2	0.0	Sub Nigra Depression2	0.0
BA7 Control	40.1	Glob Palladus Control	51.4
BA7 Control2	26.1	Glob Palladus Control2	5.1
BA7 Alzheimer's2	0.0	Glob Palladus	21.3
		Alzheimer's
BA7 Parkinson's	0.0	Glob Palladus	0.0
		Alzheimer's2
BA7 Parkinson's2	16.6	Glob Palladus	0.0
		Parkinson's
BA7 Huntington's	15.2	Glob Palladus	31.4
		Parkinson's2
BA7	0.0	Glob Palladus PSP	0.0
Huntington's2
BA7 PSP	0.0	Glob Palladus PSP2	4.5
BA7 PSP2	14.7	Glob Palladus	44.4
		Depression
BA7 Depression	4.3	Temp Pole Control	4.3
BA9 Control	7.1	Temp Pole Control2	9.5
BA9 Control2	30.8	Temp Pole Alzheimer's	3.6
BA9 Alzheimer's	0.0	Temp Pole	0.0
		Alzheimer's2
BA9 Alzheimer's2	0.0	Temp Pole Parkinson's	3.0
BA9 Parkinson's	0.0	Temp Pole Parkinson's2	19.8
BA9 Parkinson's2	33.9	Temp Pole	10.7
		Huntington's
BA9 Huntington's	37.4	Temp Pole PSP	0.0
BA9	0.0	Temp Pole PSP2	1.7
Huntington's2
BA9 PSP	0.0	Temp Pole Depression2	2.5
BA9 PSP2	1.9	Cing Gyr Control	86.5
BA9 Depression	5.2	Cing Gyr Control2	26.6
BA9 Depression2	0.0	Cing Gyr Alzheimer's	15.3
BA17 Control	28.3	Cing Gyr Alzheimer's2	13.0
BA17 Control2	20.6	Cing Gyr Parkinson's	0.0
BA17	7.0	Cing Gyr Parkinson's2	49.3
Alzheimer's2
BA17 Parkinson's	0.0	Cing Gyr Huntington's	58.6
BA17	27.2	Cing Gyr Huntington's2	0.0
Parkinson's2
BA17	23.7	Cing Gyr PSP	0.0
Huntington's
BA17	0.0	Cing Gyr PSP2	17.0
Huntington's2
BA17 Depression	24.5	Cing Gyr Depression	49.3
BA17	27.9	Cing Gyr Depression2	19.1
Depression2

[0967] AI_comprehensive panel_v1.0 Summary: Ag4413 Highest expression of this gene is seen in a sample from a patient with Crohn's disease (CT=29.4). Moderate levels of expression are also seen in a cluster of tissues derived from patients with asthma and OA. This gene encodes a protein with homology to members of the ADAMTS family. ADAMTS proteins have been implicated in extracellular proteolysis and may play a critical role in the tissue degradation seen in arthritis and other inflammatory conditions. (Martel-Pelletier J. (2001) Best Pract Res Clin Rheumatol 15(5):805-29) Therefore, therapeutic modulation of the expression or function of this gene through the use of human monoclonal antibodies or small molecule drugs may be effective in the treatment of osteoarthritis and other autoimmune diseases.

[0968] CNS_neurodegeneration_v1.0 Summary: Ag2430/Ag4413 Two experiments with two different probe and primer sets produce results that are in excellent agreement, with highest expression in the temporal cortex of an Alzheimer's patient (CTs=30-32.7). These results confirm the expression of this gene at low levels in the brain in an independent group of individuals. This gene is found to be upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0969] General_screening_panel_v1.4 Summary: Ag4413 Highest expression of this gene is seen in the cerebellum (CT=27). In addition, this gene is expressed at moderate to low levels in all regions of the CNS examined. The high levels of expression in the cerebellum suggest that this gene product may be a useful and specific target for the treatment of CNS disorders that originate in this region, such as autism and the ataxias.

[0970] Among tissues with metabolic function, this gene is expressed at moderate to low levels in adipose, pancreas, heart, and fetal skeletal muscle and liver. This expression suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0971] In addition, this gene is expressed at much higher levels in fetal kidney tissue (CT=29.6) when compared to expression in the adult counterpart (CT=30.6). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[0972] Moderate levels of expression are also seen in cell lines from brain, colon, lung, renal and melanoma cancers. Thus, expression of this gene may potentially be used as a marker of these cancers. Therapeutic modulation of this gene product may also be useful in the treatment of these cancers.

[0973] Oncology_cell_line_screening_panel_v3.2 Summary: Ag2430 Expression of the gene on this panel is limited to cerebellum and lung cancer cell lines. This is in agreement with the expression seen in Panels 1.3D and 1.4. Thus, expression of this gene could be used as a marker of cerebellar tissue and lung cancer and to differentiate these samples from other samples on this panel.

[0974] Panel 1.3D Summary: Ag2430 Expression of the gene in this panel is in agreement with expression in Panel 1.4. Highest expression is seen in the cerebellum (CT=31), with low but significant expression detected in the amygdala, hippocampus, substantia nigra and thalamus. Moderate to low levels of expression are seen in fetal skeletal muscle, adipose, and cancer cell lines derived from melanoma, breast, lung, renal, colon and brain cancers. Please see Panel 1.4 for further discussion of utility of this gene in human disease.

[0975] Panel 2D Summary: Ag2430 Highest expression of this gene is seen in lung cancer (CT=31). In addition, expression of this gene appears to be upregulated in lung, thyroid, gastric and ovarian cancer when compared to expression in the corresponding normal adjacent tissue. This protein is homologous to members of the family of ADAMTS proteins that are characterized by disintegrin, metalloproteinase and thrombospondin domains. This domain structure alone leads one to speculate that the expression of these genes in the context of cancer might play a role in the progression of the disease, as both metalloproteinases and thrombospondins have been demonstrated to be important to tumor progression. Specifically, the metalloproteinase domain may play a role in cell invasion and metastasis, and the thrombospondin domain may play a role in angiogenesis. (Masui T. Clin Cancer Res November 2001;7(11):3437-4)

[0976] Based on the expression profile of this gene and the role played by ADAMTS proteins in tumor progression, this gene in the correct context might play a role in tumor angiogeneis. Furthermore, therapeutic targeting with antibodies or small molecule drugs directed against this gene product may block the angiogenic and invasion/metastasis promoting activities of this molecule especially in those cancer types where the gene is overexpressed in the tumor compared to the normal adjacent tissue.

[0977] Panel 4.1D Summary: Ag4413/Ag7012 Three experiments with two different probe and primer set produce results that are in excellent agreement. Highest expression is seen in TNF-a and IL-1 beta treated HPAECs. This gene appears to be preferentially expressed in endothelial cells, including microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells and human umbilical vein endothelial cells. Endothelial cells are known to play important roles in inflammatory responses by altering the expression of surface proteins that are involved in activation and recruiting of effector inflammatory cells. The expression of this gene in dermal microvascular endothelial cells suggests that this protein product may be involved in inflammatory responses to skin disorders, including psoriasis. Expression in lung microvascular endothelial cells suggests that the protein encoded by this gene may also be involved in lung disorders including asthma, allergies, chronic obstructive pulmonary disease, and emphysema. The protein encoded by this gene has homology to ADAMTS family of molecules suggesting that it may function as an enzyme. Based on its homology, it may contribute to the tissue destruction and remodeling processes associated with asthma, ulcerative colitis, emphysema and osteoarthritis. (Kuno K. J Biol Chem Jan. 3, 1997;272(1):556-62;) Therefore, blocking the function of the protein encoded by this gene with human nonoclonal antibody therapeutics or small molecule therapeutics may reduce or inhibit tissue destruction in the lungs, intestine, or joints due to emphysema, allergy, asthma, colitis, or osteoarthritis.

[0978] Panel 4D Summary: Ag2430 Highest expression of the gene in this panel is seen in HUVECs (CT=28). Expression in this panel is in agreement with expression in Panel 4.1D, with preferential expression seen in endothelial cells, including HPAECs, lung and dermal microvascular ECs, and a cluster of HUVEC samples. Please see Panel 4D for discussion of this gene in inflammation.

[0979] Panel CNS—1 Summary: Ag2430 This panel confirms the presence of this gene in the brain. Please see Panels 1.4 and CNS_neurodegeneration for discussion of this gene in the central nervous system.

[0980] AJ. CG110242-01: Ebnerin

[0981] Expression of gene CG110242-01 was assessed using the primer-probe sets Ag1000 and Ag855, described in Tables AJA and AJB. Results of the RTQ-PCR runs are shown in Table AJC.

TABLE AJA
Probe Name Ag1000
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgtggtggcattattaccaact-3′	22	967	288
Probe	TET-5′-ccccacagaatgaaatgcatgaca-3′-TAMRA	24	1010	289
Reverse	5′-atttcccacacacaagtgatgt-3′	22	1034	290

[0982]

TABLE AJB
Probe Name Ag855
Primers	Sequences	Length	Position	No
Forward	5′-ggaaatgccagcagtatatgat-3′	22	1073	291
Probe	TET-5′-catttgccttgatttcccacacacaa-3′-TAMRA	26	1041	292
Reverse	5′-aatgaaatgcatgacaacatca-3′	22	1018	293

[0983]

TABLE AJC
General_screening_panel_v1.5
	Rel. Exp. (%) Ag855, Run		Rel. Exp. (%) Ag855, Run
Tissue Name	258465524	Tissue Name	258465524
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma*	0.0	Bladder	100.0
Hs688(A).T
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.)	0.0
		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell	0.0	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	23.5	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	0.0
PC-3
Prostate Pool	2.1	Colon ca. CaCo-2	0.0
Placenta	0.7	Colon cancer tissue	0.0
Uterus Pool	0.4	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	3.8	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	0.9
Ovarian ca. IGROV-1	0.6	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-	0.0	Lymph Node Pool	0.9
231
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.4
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	0.0	Thymus Pool	1.0
Trachea	0.3	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	0.0	CNS cancer (neuro; met)	1.0
		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-	0.0
		75
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	0.5	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	2.4
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.0	Brain (fetal)	5.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	3.2
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	4.6
Lung ca. NCI-H522	2.7	Brain (Substantia nigra)	9.1
		Pool
Liver	0.0	Brain (Thalamus) Pool	9.3
Fetal Liver	0.0	Brain (whole)	17.7
Liver ca. HepG2	0.0	Spinal Cord Pool	2.0
Kidney Pool	0.0	Adrenal Gland	1.9
Fetal Kidney	0.0	Pituitary gland Pool	5.7
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0984] General_screening_panel_v1.5 Summary: Ag855 Highest expression of the CG110242-01 gene is seen in the bladder (CT=31). Thus, expression of this gene could be used to differentiate this sample from other samples on this panel and as a marker of bladder tissue. In addition, low but significant levels of expression are also seen in testis, thalamus, substantia nigra, and whole brain samples. Thus, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0985] AK. CG99598-01: Endosomal Glycoprotein

[0986] Expression of gene CG99598-01 was assessed using the primer-probe sets Ag4149 and Ag4806, described in Tables AKA and AKB. Results of the RTQ-PCR runs are shown in Table AKC.

TABLE AKA
Probe Name Ag4149
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ctatactctccagccccgaat-3′	21	1001	294
Probe	TET-5′-aagcctcaggcacctccaactgct-3′-TAMRA	24	1025	295
Reverse	5′-tgatagaagaccagctgtggaa-3′	22	1070	296

[0987]

TABLE AKB
Probe Name Ag4806
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ctacgtggctctggatgatct-3′	21	2829	297
Probe	TET-5′-cctgccctcagccaggttcctgt-3′-TAMRA	23	2867	298
Reverse	5′-acacaggccagactcaaaatc-3′	21	2890	299

[0988]

TABLE AKC
General_screening_panel_v1.4
	Rel. Exp. (%) Ag4806,		Rel. Exp. (%) Ag4806,
Tissue Name	Run 223204110	Tissue Name	Run 223204110
Adipose	7.6	Renal ca. TK-10	4.4
Melanoma*	4.6	Bladder	13.7
Hs688(A).T
Melanoma*	12.7	Gastric ca. (liver met.)	6.6
Hs688(B).T		NCI-N87
Melanoma* M14	27.7	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	7.7
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	9.6
Squamous cell	0.0	Colon ca.* (SW480 met)	7.2
carcinoma SCC-4		SW620
Testis Pool	0.0	Colon ca. HT29	15.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	15.2
PC-3
Prostate Pool	3.6	Colon ca. CaCo-2	12.5
Placenta	4.7	Colon cancer tissue	15.8
Uterus Pool	0.0	Colon ca. SW1116	16.8
Ovarian ca. OVCAR-3	0.3	Colon ca. Colo-205	13.9
Ovarian ca. SK-OV-3	19.9	Co1on ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	14.2	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	24.1	Stomach Pool	1.3
Ovarian ca. OVCAR-8	23.2	Bone Marrow Pool	0.0
Ovary	0.7	Fetal Heart	17.0
Breast ca. MCF-7	6.7	Heart Pool	4.2
Breast ca. MDA-MB-	65.1	Lymph Node Pool	3.5
231
Breast ca. BT 549	18.8	Fetal Skeletal Muscle	6.5
Breast ca. T47D	100.0	Skeletal Muscle Pool	11.8
Breast ca. MDA-N	8.7	Spleen Pool	18.7
Breast Pool	1.9	Thymus Pool	12.9
Trachea	0.0	CNS cancer (glio/astro)	25.9
		U87-MG
Lung	0.0	CNS cancer (glio/astro) U-	37.9
		118-MG
Fetal Lung	19.9	CNS cancer (neuro; met)	9.3
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	3.2
Lung ca. LX-1	11.0	CNS cancer (astro) SNB-	33.4
		75
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	11.0
Lung ca. SHP-77	11.4	CNS cancer (glio) SF-295	9.8
Lung ca. A549	33.7	Brain (Amygdala) Pool	9.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	22.4
Lung ca. NCI-H23	7.0	Brain (fetal)	14.4
Lung ca. NCI-H460	9.7	Brain (Hippocampus) Pool	8.4
Lung ca. HOP-62	7.9	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	18.9
		Pool
Liver	40.1	Brain (Thalamus) Pool	8.2
Fetal Liver	5.1	Brain (whole)	3.5
Liver ca. HepG2	16.6	Spinal Cord Pool	7.8
Kidney Pool	11.5	Adrenal Gland	4.0
Fetal Kidney	16.7	Pituitary gland Pool	13.9
Renal ca. 786-0	25.7	Salivary Gland	0.8
Renal ca. A498	0.0	Thyroid (female)	1.8
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.5
Renal ca. UO-31	8.8	Pancreas Pool	11.7

[0989] General_screening_panel_v1.4 Summary: Ag4806 Expression of this gene is highest in a breast cancer cell line (CT=31.5). This gene is also expressed in breast, ovarian and colon cancer cell lines at higher levels when compared to normal tissue samples. Hence, expression of this gene might be used as a marker to identify normal tissue from cancerous tissue in these organs.

[0990] There is relatively low level of expression in most endocrine (metabolic)-related tissues except for liver. Modulation of this gene or gene-product may therefore be beneficial in treating various abnormalities related to liver function. The higher levels of expression in adult liver (CT=32.7) when compared to fetal liver suggest that expression of this gene can also be used to differentiate fetal vs adult liver tissue. Conversely, higher levels of expression in fetal lung (CT=33) when compared to adult lung (CT=40) suggest involvement of this gene in the development of the lung. Expression of this gene could also therefore be used to differentiate between fetal and adult lung tissue.

Example D: Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences

[0991] 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.

[0992] 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.

[0993] 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.

[0994] 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).

[0995] 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.

[0996] NOV1a SNP Data

[0997] One polymorphic variant of NOV1a has been identified and is shown in Table 42A.

	TABLE 42A
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379178	120	A	G	30	Pro	Pro

[0998] NOV2a SNP Data

[0999] One polymorphic variant of NOV2a has been identified and is shown in Table 42B.

	TABLE 42B
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379271	2850	C	T	909	Asp	Asp

[1000] NOV5a SNP Data

[1001] One polymorphic variant of NOV5a has been identified and is shown in Table 42C.

	TABLE 42C
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379181	1001	G	C	Silent	N/A	N/A

[1002] NOV6a SNP Data

[1003] Seven polymorphic variant of NOV6a have been identified and is shown in Table 42D.

	TABLE 42D
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379177	1599	C	T	Silent	N/A	N/A
13379176	1665	G	T	Silent	N/A	N/A
13379175	1673	G	A	Silent	N/A	N/A
13379174	1732	G	A	Silent	N/A	N/A
13379173	1791	G	T	Silent	N/A	N/A
13379172	1795	G	A	Silent	N/A	N/A
13379171	1876	T	C	Silent	N/A	N/A

[1004] NOV9a SNP Data

[1005] Two polymorphic variant of NOV9a have been identified and are shown in Table 42E.

	TABLE 42E
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379179	191	A	G	59	Thr	Thr
13379180	360	G	C	116	Val	Leu

[1006] NOV9b SNP Data

[1007] Three polymorphic variant of NOV9b have been identified and are shown in Table 42F.

	TABLE 42F
	Nucleotides	Amino Acids
	Base Position			Base Position
Variant No.	of SNP	Wild-type	Variant	of SNP	Wild-type	Variant
13379251	971	A	G	315	Ala	Ala
13379250	1226	C	T	400	Gly	Gly
13379249	1712	C	T	562	Tyr	Tyr

[1008] NOV10a SNP Data

[1009] Eight polymorphic variant of NOV10a have been identified and are shown in Table 42G.

	TABLE 42G
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13376858	229	A	G	74	Glu	Gly
13376859	258	G	A	84	Ala	Thr
13376860	286	A	G	93	Gln	Arg
13376861	296	T	C	96	Ala	Ala
13376862	305	A	G	99	Gln	Gln
13376863	312	A	G	102	Thr	Ala
13376864	348	A	G	114	Arg	Gly
13376866	404	G	A	132	Met	Ile

[1010] NOV11a SNP Data

[1011] Two polymorphic variant of NOV11a have been identified and are shown in Table 42H.

	TABLE 42H
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379186	346	T	C	96	Ser	Ser
13379187	539	A	G	161	Ile	Val

[1012] NOV15a SNP Data

[1013] Three polymorphic variant of NOV15a have been identified and are shown in Table 42I.

	TABLE 42I
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13377489	243	T	C	71	Tyr	Tyr
13377488	348	C	T	106	Ile	Ile
13377487	723	T	G	231	Thr	Thr

[1014] NOV16a SNP Data

[1015] One polymorphic variant of NOV16a has been identified and is shown in Table 42J.

	TABLE 42J
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379185	1258	A	G	415	Ser	Ser

[1016] NOV17a SNP Data

[1017] One polymorphic variant of NOV17a has been identified and is shown in Table 42K.

	TABLE 42K
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379184	229	A	G	76	Met	Val

[1018] NOV19a SNP Data

[1019] Two polymorphic variants of NOV19a have been identified and are shown in Table 42L.

	TABLE 42L
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379188	3620	T	C	1187	Val	Ala
13379189	3725	G	A	Silent	N/A	N/A

[1020] NOV27a SNP Data

[1021] One polymorphic variant of NOV27a has been identified and is shown in Table 42M.

	TABLE 42M
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379191	2068	T	C	364	Pro	Pro

[1022] NOV29a SNP Data

[1023] One polymorphic variant of NOV29a has been identified and is shown in Table 42N.

	TABLE 42N
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379190	113	C	T	25	Pro	Leu

[1024] NOV31a SNP Data

[1025] One polymorphic variant of NOV31a has been identified and is shown in Table 42O.

	TABLE 42O
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379285	923	C	T	307	Phe	Phe

[1026] NOV35a SNP Data

[1027] One polymorphic variant of NOV35a has been identified and is shown in Table 42P.

	TABLE 42P
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13378787	1271	C	T	424	Ala	Val

[1028] NOV39a SNP Data

[1029] Five polymorphic variant of NOV39a have been identified and are shown in Table 42Q.

	TABLE 42Q
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379193	655	T	C	191	Tyr	His
13379196	861	A	G	259	Lys	Lys
13379195	871	A	G	263	Lys	Glu
13374732	1425	T	C	447	Asp	Asp
13379194	1960	T	A	626	Leu	Ile

Example E: Potential Role(s) of CG102615-01 in Tumorgenesis

[1030] The NOV13a gene (CG102615-01) is known to mediate chloride flow, affecting the membrane potential of the cell. Changes in membrane potential can affect tumor cell and associated smooth muscle cells (therefore tumor-induced vasculature) growth and motility. In this respect, the strong expression in fetal muscle is an indication of a role for NOV13a in muscle growth/development.

[1031] Therapeutic targeting of NOV13a with a human monoclonal antibody is anticipated to limit or block the extent of tumor cell growth and motility and tumor associated angiogenesis, preferably in breast, ovarian bladder, lung tumors.

[1032] SAGE data is present for NOV13a in Table 43.

TABLE 43
NOV13a SAGE data
Hs 301350: FXYD domain-containing ion transport regulator 3
SAGE library data and reliable tag summary
Reliable tags found in SAGE libraries
	Tags per	Tag
Library name	million	counts	Total tags
AACCGAAAAA
SAGE Caco 2	16	1	61601
SAGE Chen LNCaP	32	2	62267
SAGE Chen LNCaP no-DHT	15	1	64631
SAGE Chen Tumor Pr	14	1	68384
SAGE CAPAN1	52	2	37926
SAGE Duke GBM H1110	14	1	70061
SAGE SW837	16	1	60986
SAGE PR317 normal prostate	16	1	59419
SAGE PR317 prostate tumor	46	3	65109
SAGE pooled GBM	16	1	61841
SAGE NHA(5th)	19	1	52196
SAGE NC1	19	1	50115
SAGE NC2	141	7	49552
SAGE Panc 91-16113	88	3	33941
SAGE Tu102	34	2	57636
SAGE Tu98	61	3	49005
SAGE SciencePark MCF7	163	10	61079
Control 0 h
SAGE SciencePark MCF7	33	2	59978
estradiol 3 h
SAGE 95-259	25	1	39473
SAGE 95-260	22	1	45179
SAGE 95-348	33	2	60484
SAGE Medullo 3871	115	5	43274
SAGE MouseP8 PGCP	16	1	61240
SAGE MDA453	52	1	18924
SAGE Duke HMVEC + VEGF	17	1	57928
SAGE DCIS	218	9	41230
SAGE OVT-8	29	1	33575
SAGE DCIS 2	34	1	28888
GCAGGGCCTC
SAGE Caco 2	16	1	61601
SAGE Chen LNCaP	208	13	62267
SAGE Chen LNCaP no-DHT	278	18	64631
SAGE Chen Normal Pr	196	13	66193
SAGE Chen Tumor Pr	102	7	68384
SAGE CAPAN1	632	24	37926
SAGE CAPAN2	473	11	23222
SAGE SW837	196	12	60986
SAGE CPDR LNCaP-C	48	2	41590
SAGE PR317 normal prostate	521	31	59419
SAGE PR317 prostate tumor	2042	133	65109
SAGE NC1	2554	128	50115
SAGE NC2	3329	165	49552
SAGE Panc 91-16113	824	28	33941
SAGE Panc 96-6252	111	4	35745
SAGE OV1063-3	154	6	38938
SAGE Tu102	884	51	57636
SAGE Tu98	938	46	49005
SAGE SciencePark MCF7	677	4	5903
control 3 h
SAGE SciencePark MCF7	343	21	61079
Control 0 h
SAGE ScincePark MCF7	233	14	59978
estradiol 3 h
SAGE SciencePark MCF7	215	13	60435
estradiol 10 h
SAGE lacZ	377	7	18528
SAGE PTEN	213	2	9380
SAGE 95-347	431	29	67240
SAGE 95-259	608	24	39473
SAGE 95-260	420	19	45179
SAGE 95-348	942	57	60484
SAGE PrCA-1	109	1	9105
SAGE normal prostate	152	2	13148
SAGE LNCaP	132	3	22637
SAGE OVT-6	23	1	42336
SAGE H1126	57	1	17501
SAGE OVT-7	200	11	54914
SAGE MDA453	264	5	18924
SAGE SKBR3	735	6	8153
SAGE mammary epithelium	386	19	49167
SAGE DCIS	2328	96	41230
SAGE normal cerebellum	22	1	44421
SAGE OVT-8	59	2	33575
SAGE Duke 40N	280	2	7142
SAGE Duke 48N	82	1	12091
SAGE Duke post crisis	13	1	71792
fibroblasts
SAGE DCIS 2	1557	45	28888
SAGE Br N	532	20	37558
SAGE A+	130	4	30551

OTHER EMBODIMENTS

[1033] Although particular embodiments have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims, which follow. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the invention without departing from the spirit and scope of the invention as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. 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 sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 73.

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 73.

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 73.

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 73.

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 73 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 73.

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 73.

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 73.

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 73.

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 73, 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. The antibody of claim 29, wherein the antibody is a fully human antibody.

33. The antibody of claim 29, wherein the dissociation constant for the binding of the polypeptide to the antibody is less than 1×10−9 M.

34. The antibody of claim 29, wherein the antibody neutralizes an activity of the polypeptide.

35. A method of treating or preventing a NOVX-associated disorder, the method comprising administering to a subject in which such treatment or prevention is desired the antibody of claim 29 in an amount sufficient to treat or prevent the pathology in the subject.

36. The method of claim 35, wherein the subject is human.

37. 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.

38. The method of claim 37 wherein presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.

39. The method of claim 38 wherein the cell or tissue type is cancerous.

40. 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.

41. 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 73.

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.

46. 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 73.

47. The method of claim 46 wherein the cell is a bacterial cell.

48. The method of claim 46 wherein the cell is an insect cell.

49. The method of claim 46 wherein the cell is a yeast cell.

50. The method of claim 46 wherein the cell is a mammalian cell.