Novel human proteins, polynucleotides encoding them and methods of using the same

Abstract

Disclosed herein are nucleic acid sequences that encode novel polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, and antibodies that immunospecifically bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the novel polypeptide, polynucleotide, or antibody specific to the polypeptide. Vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using same are also included. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

Description

FIELD OF THE INVENTION

[0002] The present invention relates to nucleic acids encoding proteins that are new members of the following protein families: MAP kinase phosphatase-like proteins, cyclin-like proteins, GAG-like proteins, RasGEF domain containing proteins, novel Guanine-nucleotide exchange factor-like proteins, MAXP1-like proteins, Retinoblastoma binding protein p48-like proteins, XAF-1-like proteins (with zinc finger motifs), novel XIAP-associated Factor 1-like proteins, profilin-like proteins, syntenin-2BETA-like proteins, PLK Interacting protein-like proteins, intercellular protein-like proteins, Adenosine-deaminase (editase)-like proteins, Leiomodin-like proteins, Faciogenital dysplasia Factor 3-like proteins, collybistin 1-like proteins, splice variant of N-terminal kinase-like (NTKL)-like proteins, neurobeachin-like proteins, leucine-rich repeat protein-like proteins, synaptotagmin-like proteins, granuphilin A-like proteins, nuclear dual-specificity phsophatase-like proteins, zinc finger (C2H2) domain-like proteins, NADH-Ubiquinone Oxidoreductase 13 KDA-B subunit-like proteins, 1700003M02RIK protein-like proteins, Negative Regulator Of Translation-like proteins, 4E-Binding, Protein 2-like proteins, hypothetical intracellular proteins, CAP-Gly domain-containing proteins, Differentiation Enhancing Factor 1-like proteins, C2-domain containing, proteins, Oxystyrol-binding protein homolog 1-like proteins, Channel interacting PDZ domain-like proteins, and Similar to SRC homology (SH3) and Cysteine-rich Domain protein-like proteins.

[0003] Included in the invention are polynucleotides and the polypeptides encoded by such polynucleotides, as well as vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using the same. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions.

BACKGROUND OF THE INVENTION

[0004] The invention generally relates to nucleic acids and polypeptides encoded therefrom. More specifically, the invention relates to nucleic acids encoding cytoplasmic, nuclear, membrane bound, and secreted polypeptides, as well as vectors, host cells, antibodies, and recombinant methods for producing these nucleic acids and polypeptides.

SUMMARY OF THE INVENTION

[0005] The present invention is based in part on nucleic acids encoding proteins that are members of the following protein families: MAP kinase phosphatase-like proteins, cyclin-like proteins, GAG-like proteins, RasGEF domain containing proteins, novel Guanine-nucleotide exchange factor-like proteins, MAXP1-like proteins, Retinoblastoma binding protein p48-like proteins, XAF-1 Zinc finger-like proteins, novel XIAP-associated Factor l-like proteins, profilin-like proteins, syntenin-2BETA-like proteins, PLK Interacting protein-like proteins, intracellular protein-like proteins, Adenosine-deaminase (editase)-like proteins, Leiomodin-like proteins, Faciogenital dysplasia Factor 3-like proteins, collybistin 1-like proteins, splice variant of N-terminal kinase-like (NTKL)-like proteins, neurobeachin-like proteins, leucine-rich repeat protein-like proteins, synaptotagmin-like proteins, granuphilin A-like proteins, nuclear dual-specificity phsophatase-like proteins, zinc finger (C2H2) domain-like proteins, NADH-Ubiquinone Oxidoreductase 13 KDA-B subunit-like proteins, 1700003M02RIK protein-like proteins, Negative Regulator Of Translation-like proteins, 4E-Binding Protein 2-like proteins, hypothetical intracellular proteins, CAP-Gly domain-containing proteins, Differentiation Enhancing Factor 1-like proteins, C2-domain containing proteins, Oxystyrol-binding protein homolog 1-like proteins, Channel interacting PDZ domain-like proteins, and Similar to SRC homology (SH3) and Cysteine-rich Domain protein-like proteins. The novel polynucleotides and polypeptides are referred to herein as NOV1a, NOV2a, NOV2b, NOV3a, NOV4a, NOV4b, NOV5a, NOV6a, NOV7a, NOV7b, NOV8a, NOV8b, NOV9a, NOV10a, NOV10b, NOV11a, NOV12a, NOV13a, NOV14a, NOV15a, NOV16a, NOV17a, NOV18a, NOV18b, NOV19a, NOV20a, NOV21a, NOV22a, NOV23a, NOV24a, NOV25a, NOV26a, NOV27a, NOV28a, NOV29a, NOV30a, NOV31a, NOV32a, NOV33a, NOV34a, NOV35a, NOV35b, NOV36a, NOV36b. 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.

[0006] In one aspect, the invention provides an isolated NOVX nucleic acid disclosed in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44. In some embodiments, the NOVX nucleic acid molecule will hybridize under stringent conditions to a nucleic acid sequence complementary to a nucleic acid molecule that includes a protein-coding sequence of a NOVX nucleic acid sequence. The invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof. For example, the nucleic acid can encode a polypeptide at least 80% identical to a polypeptide comprising the amino acid sequences of SEQ ID NO:2n, wherein n is an integer between 1 and 44. The nucleic acid can be, for example, a genomic DNA fragment or a cDNA molecule that includes the nucleic acid sequence of any of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44. Also included in the invention is an oligonucleotide, e.g. an oligonucleotide which includes at least 6 contiguous nucleotides of a NOVX nucleic acid (e.g., SEQ ID NO:2n-1, wherein n is an integer between 1 and 44) or a complement of said oligonucleotide.

[0007] The invention also encompasses isolated NOVX polypeptides (SEQ ID NO:2n, wherein n is an integer between 1 and 44). In certain embodiments, the NOVX polypeptides include an amino acid sequence that is substantially identical to the amino acid sequence of a human NOVX polypeptide.

[0008] The invention also features antibodies that immunoselectively bind to NOVX polypeptides, or fragments, homologs, analogs or derivatives thereof.

[0009] 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.

[0010] In a further aspect, the invention includes a method of producing a polypeptide by culturing a cell that includes a NOVX nucleic acid, under conditions allowing for expression of the NOVX polypeptide encoded by the DNA. If desired, the NOVX polypeptide can then be recovered.

[0011] In another aspect, the invention includes a method of detecting the presence of a NOVX polypeptide in a sample. In the method, a sample is contacted with a compound that selectively binds to the polypeptide under conditions allowing for formation of a complex between the polypeptide and the compound. The complex is detected, if present, thereby identifying the NOVX polypeptide within the sample.

[0012] The invention also includes methods to identify specific cell or tissue types based on their expression of a NOVX.

[0013] Also included in the invention is a method of detecting the presence of a NOVX nucleic acid molecule in a sample by contacting the sample with a NOVX nucleic acid probe or primer, and detecting whether the nucleic acid probe or primer bound to a NOVX nucleic acid molecule in the sample.

[0014] In a further aspect, the invention provides a method for modulating the activity of a NOVX polypeptide by contacting a cell sample that includes the NOVX polypeptide with a compound that binds to the NOVX polypeptide in an amount sufficient to modulate the activity of said polypeptide. The compound can be, e.g., a small molecule, such as a nucleic acid, peptide, polypeptide, peptidomimetic, carbohydrate, lipid or other organic (carbon containing) or inorganic molecule, as further described herein.

[0015] In another embodiment, the invention involves a method for identifying a potential therapeutic agent for use in treatment of a pathology, herein the pathology is related to aberrant expression or aberrant physiological interactions of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44, the method including providing a cell expressing the polypeptide of the invention and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent.

[0016] Also within the scope of the invention is the use of a therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e.g., adrenoleukodystrophy, congenital adrenal hyperplasia, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, autoimmune disease, allergies, immunodeficiencies, Von Hippel-Lindau (VHL) syndrome, Alzheimer's disease, stroke, tuberous sclerosis, hypercalcemia, Parkinson's disease, Huntington's disease, cerebral palsy, epilepsy, Lesch-Nyhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, diabetes, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus renal tubular acidosis, IgA nephropathy, asthma, emphysema, scleroderma, adult respiratory distress syndrome (ARDS), lymphedema, graft versus host disease (GVHD), pancreatitis, obesity, ulcers, anemia, ataxia-telangiectasia, cancer, trauma, viral infections, bacterial infections, parasitic infections; and conditions related to transplantation, neuroprotection, fertility, or regeneration (in vitro and in vivo), faciogenital dysplasia and/or other pathologies and disorders of the like. Also within the scope of the invention is the use of a therapeutic in the manufacture of a medicament for treating or preventing conditions including, e.g., those associated with homologs of a NOVX sequence, such as those listed in Table A.

[0017] The therapeutic can be, e.g., a NOVX nucleic acid, a NOVX polypeptide, or a NOVX-specific antibody, or biologically-active derivatives or fragments thereof.

[0018] For example, the compositions of the present invention will have efficacy for treatment of patients suffering from the diseases and disorders disclosed above and/or other pathologies and disorders of the like. The polypeptides can be used as immunogens to produce antibodies specific for the invention, and as vaccines. They can also be used to screen for potential agonist and antagonist Compounds. For example, a cDNA encoding NOVX may be useful in gene therapy, and NOVX may be useful when administered to a subject in need thereof.

[0019] The invention further includes a method for screening for a modulator of disorders or syndromes including, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like. The method includes contacting a test compound with a NOVX polypeptide and determining if the test compound binds to said NOVX polypeptide. Binding of the test compound to the NOVX polypeptide indicates the test compound is a modulator of activity, or of latency or predisposition to the aforementioned disorders or syndromes.

[0020] Also within the scope of the invention is a method for screening for a modulator of activity, or of latency or predisposition to disorders or syndromes including, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like by administering a test compound to a test animal at increased risk for the aforementioned disorders or syndromes. The test animal expresses a recombinant polypeptide encoded by a NOVX nucleic acid. Expression or activity of NOVX polypeptide is then measured in the test animal, as is expression or activity of the protein in a control animal which recombinantly-expresses NOVX polypeptide and is not at increased risk for the disorder or syndrome. Next, the expression of NOVX polypeptide in both the test animal and the control animal is compared. A change in the activity of NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of the disorder or syndrome.

[0021] 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, a NOVX nucleic acid, or both, in a subject (e.g., a human subject). The method includes measuring the amount of the NOVX polypeptide in a test sample from the subject and comparing the amount of the polypeptide in the test sample to the amount of the NOVX polypeptide present in a control sample. An alteration in the level of the NOVX polypeptide in the test sample as compared to the control sample indicates the presence of or predisposition to a disease in the subject. Preferably, the predisposition includes, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like. Also, the expression levels of the new polypeptides of the invention can be used in a method to screen for various cancers as well as to determine the stage of cancers.

[0022] In a further aspect, the invention includes a method of treating or preventing a pathological condition associated with a disorder in a mammal by administering to the subject a NOVX polypeptide, a NOVX nucleic acid, or a NOVX-specific antibody to a subject (e.g., a human subject), in an amount sufficient to alleviate or prevent the pathological condition. In preferred embodiments, the disorder, includes, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like.

[0023] In yet another aspect, the invention can be used in a method to identity the cellular receptors and downstream effectors of the invention by any one of a number of techniques commonly employed in the art. These include but are not limited to the two-hybrid system, affinity purification, co-precipitation with antibodies or other specific-interacting molecules.

[0024] NOVX nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel NOVX substances for use in therapeutic or diagnostic methods. These NOVX antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the “Anti-NOVX Antibodies” section below. The disclosed NOVX proteins have multiple hydrophilic regions, each of which can be used as an immunogen. These NOVX proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.

[0025] The NOVX nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below. The potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.

[0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

[0027] Other features and advantages of the invention will be apparent from the following detailed description and claims.

DETAILED DESCRIPTION OF THE INVENTION

[0028] The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds. The sequences are collectively referred to herein as “NOVX nucleic acids” or “NOVX polynucleotides” and the corresponding encoded polypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.” Unless indicated otherwise, “NOVX” is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides.

TABLE A
Sequences and Corresponding SEQ ID Numbers
		SEQ ID	SEQ
		NO	ID NO
NOVX	Internal	(nucleic	(amino
Assignment	Identification	acid)	acid)	Homology
1a	CC102071-01	1	2	MAP kinase phosphatase-like
2a	CG112767-01	3	4	Cyclin-like
2b	CG112767-02	5	6	Cyclin-like
3a	CG112776-01	7	8	Gag-like
4a	CG122759-01	9	10	RasGEF domain containing protein-like
4b	CG122759-02	11	12	Novel Guanine nucleotide exchange
				factor-like
5a	CG124599-01	13	14	MAXP1-like
6a	CG125142-01	15	16	Retinoblastoma Binding Protein P48-like
7a	CG125414-01	17	18	XAF-1 zinc finger motif-like
7b	CG125414-02	19	20	Novel XIAP Associated Factor 1-like
8a	CG127770-01	21	22	Profilin 1-like
8b	CG127770-02	23	24	Profilin 1-like
9a	CG127897-01	25	26	Syntenin 2BETA-like
10a	CG127936-01	27	28	PLK interacting protein-like
10b	CG127936-02	29	30	PLK interacting protein-like
11a	CG127954-01	31	32	Intracellular protein-like
12a	CC128132-01	33	34	RAL-A Exchange Factor RALCPS2-like
13a	CGl28219-01	35	36	Adenosine-deaminase (editase)-like
14a	CG128389-01	37	38	Leiomodin-like
15a	CG128613-01	39	40	Faciogenital dysplasia protein 3-like
16a	CG128685-01	41	42	Collybistin 1-like
17a	CG128937-01	43	44	splice variant of N-terminal kinase-like
				(NTKL) like
18a	CG132095-01	45	46	Intracellular protein-like
18b	CG132095-02	47	48	Intracellular protein-like
19a	CG132414-01	49	50	Neurobeachin-like
20a	CG133140-01	51	52	Leucine-rich repeat protein-like
21a	CG133369-01	53	54	Synaptotagmin-like
22a	CG133456-01	55	56	Granuphilin-A-like
23a	CG133903-01	57	58	Nuclear dual-specificity phosphatase-like
24a	CG133995-01	59	60	Zinc finger (C2H2) domain like
25a	CC134005-01	61	62	NADH-Ubiquinone Oxidoreductase 13
				KDA-B Subunit like
26a	CG134014-01	63	64	1700003M02R1K Protein-like
27a	CG134023-01	65	66	Negative Regulator of Translation-like
28a	CG134032-01	67	68	4E-binding Protein 2-like
29a	CG134304-01	69	70	Hypothetical Intracellular Protein-like
30a	CG134421-01	71	72	CAP-Gly domain containing protein-like
31a	CC134895-01	73	74	Differentiation Enhancing Factor 1-like
32a	CG134922-01	75	76	C2 domain containing protein-like
33a	CG135070-01	77	78	Oxystyrol binding protein homolog-like
34a	CG172478-01	79	80	Channel interacting PDZ domain-like
35a	CG172549-01	81	82	Similar to SRC homology (SH3) and
				cysteine rich domain protein-like
35b	CG172549-02			Similar to SRC homology (SH3) and
				cysteine rich domain protein-like
36a	CG59828-01	85	86	EDRK-rich factor 1-like
36b	172146552	87	88	EDRK-rich factor 1-like

[0029] Table A indicates the homology of NOVX polypeptides to known protein families. Thus, the nucleic acids and polypeptides, antibodies and related compounds according to the invention corresponding to a NOVX as identified in column 1 of Table A will be useful in therapeutic and diagnostic applications implicated in, for example, pathologies and disorders associated with the known protein families identified in column 5 of Table A.

[0030] Pathologies, diseases, disorders and condition and the like that are associated with NOVX sequences include, but are not limited to: e.g., cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, metabolic disturbances associated with obesity, transplantation, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn's disease; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation and fertility.

[0031] 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.

[0032] Consistent with other known members of the family of proteins, identified in column 5 of Table A, the NOVX polypeptides of the present invention show homology to, and contain domains that are characteristic of, other members of such protein families. Details of the sequence relatedness and domain analysis for each NOVX are presented in Example A.

[0033] The NOVX nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVX activity or function. Specifically, the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit diseases associated with the protein families listed in Table A.

[0034] 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.

[0035] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.

[0036] NOVX Clones

[0037] 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.

[0038] 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.

[0039] The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. These include serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo (vi) a biological defense weapon.

[0040] 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 44; (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 44, 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 44; (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 44 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).

[0041] 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 44; (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 44 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 44; (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 44, 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 44 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.

[0042] 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 44; (b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2-n, wherein n is an integer between 1 and 44 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 44; 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 44 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.

[0043] NOVX Nucleic Acids and Polypeptides

[0044] One aspect of the invention pertains to isolated nucleic acid molecules that encode NOVX polypeptides or biologically active portions thereof. Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify NOVX-encoding nucleic acids (e.g., NOVX mRNAs) and fragments for use as PCR primers for the amplification and/or mutation of NOVX nucleic acid molecules. As used herein, the term “nucleic acid molecule” is intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs, and derivatives, fragments and homologs thereof. The nucleic acid molecule may be single-stranded or double-stranded, but preferably is comprised double-stranded DNA.

[0045] A NOVX nucleic acid can encode a mature NOVX polypeptide. As used herein, a “mature” form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full-length gene product encoded by the corresponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein. The product “mature” form arises, by way of nonlimiting example, as a result of one or more naturally occurring processing steps that may take place within the cell (e.g., host cell) in which the gene product arises. Examples of such processing steps leading to a “mature” form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having, residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+1 to residue N remaining. Further as used herein, a “mature” form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination of any of them.

[0046] The term “probe”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), about 100 nt, or as many as approximately, e.g., 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single-stranded or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.

[0047] The term “isolated” nucleic acid molecule, as used herein, is a nucleic acid that is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5′- and 3′-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.). Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium, or of chemical precursors or other chemicals.

[0048] A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or a complement of this nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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.)

[0049] A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template with appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding, to NOVX nucleotide sequences can be prepared by standard synthetic techniques, e.g. using an automated DNA synthesizer.

[0050] As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.

[0051] In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or a portion of this nucleotide sequence (e.g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of a NOVX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, that it can hydrogen bond with few or no mismatches to the nucleotide sequence shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, thereby forming, a stable duplex.

[0052] 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.

[0053] A “fragment” provided herein is defined as a sequence of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, and is at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice.

[0054] 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.

[0055] A “derivative” is a nucleic acid sequence or amino acid sequence formed from the native compounds either directly, by modification or partial substitution. An “analog” is a nucleic acid sequence or amino acid sequence that has a structure similar to, but not identical to, the native compound, e.g. they differs from it in respect to certain components or side chains. Analogs may be synthetic or derived from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. A “homolog” is a nucleic acid sequence or amino acid sequence of a particular gene that is derived from different species.

[0056] Derivatives and analogs may be full length or other than full length. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the proteins under stringent, moderately stringent, or low stringent conditions. See e.g. Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, N.Y. 1993, and below.

[0057] A “homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences include those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for a NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein. Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.

[0058] A NOVX polypeptide is encoded by the open reading frame (“ORF”) of a NOVX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG “start” codon and terminates with one of the three “stop” codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bona fide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.

[0059] The nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g. from other tissues, as well as NOVX homologues from other vertebrates. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44; or of a naturally occurring mutant of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.

[0060] Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In various embodiments, the probe has a detectable label attached, e.g. the label can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express a NOVX protein, such as by measuring a level of a NOVX-encoding nucleic acid in a sample of cells from a subject e.g., detecting NOVX mRNA levels or determining whether a genomic NOVX gene has been mutated or deleted.

[0061] “A polypeptide having a biologically-active portion of a NOVX polypeptide” refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a “biologically-active portion of NOVX” can be prepared by isolating a portion of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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.

[0062] NOVX Nucleic Acid and Polypeptide Variants

[0063] The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 44.

[0064] In addition to the human NOVX nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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.

[0065] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from a human SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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.

[0066] Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least 6 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences at least about 65% homologous to each other typically remain hybridized to each other.

[0067] 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.

[0068] 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.

[0069] Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6× SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65° C., followed by one or more washes in 0.2× SSC, 0.01% BSA at 50° C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to a sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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).

[0070] In a second embodiment, a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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.

[0071] In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting, example of low stringency hybridization conditions are hybridization in 35% formamide, 5× SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2× SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons. NY, and Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY; Shilo and Weinberg, 1981, Proc Natl Acad Sci USA 78: 6789-6792.

[0072] Conservative Mutations

[0073] In addition to naturally-occurring allelic variants of NOVX sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, thereby leading to changes in the amino acid sequences of the encoded NOVX protein, without altering the functional ability of that NOVX protein. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 44. A “non-essential” amino acid residue is a residue that can be altered from the wild-type sequences of the NOVX proteins without altering their biological activity, whereas an “essential” amino acid residue is required for such biological activity. For example, amino acid residues that are conserved among the NOVX proteins of the invention are predicted to be particularly non-amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.

[0074] Another aspect of the invention pertains to nucleic acid molecules encoding NOVX proteins that contain changes in amino acid residues that are not essential for activity. Such NOVX proteins differ in amino acid sequence from SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 40% homologous to the amino acid sequences of SEQ ID NO:2n, wherein n is an integer between 1 and 44. Preferably, the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44; more preferably at least about 70% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44.

[0075] An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 44, can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

[0076] Mutations can be introduced any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted, non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined within the art. These families include amino acids with basic side chains (e.g. lysine, arginine, histidine), acidic side chains (e.g. aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g. threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity. Following mutagenesis of a nucleic acid of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

[0077] 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.

[0078] 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).

[0079] 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).

[0080] Antisense Nucleic Acids

[0081] Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or fragments, analogs or derivatives thereof. An “antisense” nucleic acid comprises a nucleotide sequence that is complementary to a “sense” nucleic acid encoding a protein (e.g. complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of a NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 44, or antisense nucleic acids complementary to a NOVX nucleic acid sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, are additionally provided.

[0082] 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).

[0083] 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).

[0084] Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-carboxymethylaminomethyl-2-thiouridine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl)uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e. RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).

[0085] 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.

[0086] In yet another embodiment, the antisense nucleic acid molecule of the invention is an -anomeric nucleic acid molecule. An -anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual -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.

[0087] Ribozymes and PNA Moieties

[0088] 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.

[0089] In one embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988, Nature 334: 585-591) can be used to catalytically cleave NOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. A ribozyme having specificity for a NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of a NOVX cDNA disclosed herein (i.e., SEQ ID NO:2n-1, wherein n is an integer between 1 and 44). 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.

[0090] 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.

[0091] 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.

[0092] 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).

[0093] 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 sediment 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.

[0094] 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.

[0095] NOVX Polypeptides

[0096] A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in any one of SEQ ID NO:2n, wherein n is an integer between 1 and 44. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in any one of SEQ ID NO:2n, wherein n is an integer between 1 and 44, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

[0097] 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. An amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.

[0098] 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.

[0099] 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.

[0100] 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.

[0101] Biologically-active portions of NOVX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the NOVX proteins (e.g. the amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 44) 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 mote amino acid resides in length.

[0102] 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.

[0103] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 44. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 44, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below. Accordingly, in another embodiment, the NOVX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 44, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1 and 44.

[0104] Determining Homology Between Two or More Sequences

[0105] 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”).

[0106] The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970, J Mol Biol 48: 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison: GAP creation penalty of 5.0 and GAP extension penalty of 0.3, the coding region of the analogous nucleic acid sequences referred to above exhibits a degree of identity preferably of at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.

[0107] 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.

[0108] Chimeric and Fusion Proteins

[0109] The invention also provides NOVX chimeric or fusion proteins. As used herein, a NOVX “chimeric protein” or “fusion protein” comprises a NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An “NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 44, 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.

[0110] 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.

[0111] 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.

[0112] 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.

[0113] 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.

[0114] NOVX Agonists and Antagonists

[0115] 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.

[0116] 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.

[0117] Polypeptide Libraries

[0118] 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.

[0119] 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.

[0120] Anti-NOVX Antibodies

[0121] Included in the invention are antibodies to NOVX proteins, or fragments of NOVX proteins. The term “antibody” as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e. molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, Fab, Fab and F(ab′)2 fragments, and an Fab expression library. In general, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgG1, IgG2, and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.

[0122] An isolated protein of the invention intended to serve as an antigen, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that immunospecifically bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation. The full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as immunogens. An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 44, 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.

[0123] In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX that is located on the surface of the protein, e.g. a hydrophilic region. A hydrophobicity analysis of the human NOVX protein sequence will indicate which regions of a NOVX polypeptide are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production. As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g. Hopp and Woods, 1981, Proc. Natl 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.

[0124] The tern “epitope” includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. A NOVX polypeptide or a fragment thereof comprises at least one antigenic epitope. An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (KD) is ≦1 μM, preferably ≦100 nM, more preferably ≦10 nM, and most preferably ≦100 pM to about 1 pM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art.

[0125] 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.

[0126] 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.

[0127] Polyclonal-Antibodies

[0128] 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).

[0129] 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).

[0130] Monoclonal Antibodies

[0131] 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 antigen binding site capable of immunoreacting with a particular epitope of the antigen characterized by a unique binding affinity for it.

[0132] 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.

[0133] 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.

[0134] 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).

[0135] 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.

[0136] 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.

[0137] The monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.

[0138] 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

[0139] Humanized Antibodies

[0140] 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)).

[0141] Human Antibodies

[0142] 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).

[0143] 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)).

[0144] 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 immunoglobulin 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.

[0145] 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.

[0146] 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.

[0147] 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.

[0148] Fab Fragments and Single Chain Antibodies

[0149] 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.

[0150] Bispecific Antibodies

[0151] 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.

[0152] 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).

[0153] 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).

[0154] 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.

[0155] 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 mercaptoethlylamine 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.

[0156] 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.

[0157] 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).

[0158] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[0159] 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).

[0160] Heteroconjugate Antibodies

[0161] 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.

[0162] Effector Function Engineering

[0163] 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: 144-1195 (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).

[0164] Immunoconjugates

[0165] 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).

[0166] 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.

[0167] 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.

[0168] 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.

[0169] Immunoliposomes

[0170] 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.

[0171] 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).

[0172] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention

[0173] In one embodiment, methods for the screening of antibodies that possess the desired specificity include, but are not limited to, enzyme linked immunosorbent assay (ELISA) and other immunologically mediated techniques known within the art. In a specific embodiment, selection of antibodies that are specific to a particular domain of an NOVX protein is facilitated by generation of hybridomas that bind to the fragment of an NOVX protein possessing such a domain. Thus, antibodies that are specific for a desired domain within an NOVX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.

[0174] Antibodies directed against a NOVX protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of a NOVX protein (e.g., for use in measuring levels of the NOVX protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies specific to a NOVX protein, or derivative, fragment, analog or homolog thereof, that contain the antibody derived antigen binding domain, are utilized as pharmacologically active compounds (referred to hereinafter as “Therapeutics”).

[0175] An antibody specific for a NOVX protein of the invention (e.g., a monoclonal antibody or a polyclonal antibody) can be used to isolate a NOVX polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation. An antibody to a NOVX polypeptide can facilitate the purification of a natural NOVX antigen from cells, or of a recombinantly produced NOVX antigen expressed in host cells. Moreover, such an anti-NOVX antibody can be used to detect the antigenic NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic NOVX protein. Antibodies directed against a NOVX protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling, (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, -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.

[0176] Antibody Therapeutics

[0177] 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.

[0178] 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.

[0179] 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.

[0180] Pharmaceutical Compositions of Antibodies

[0181] 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.

[0182] 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.

[0183] 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.

[0184] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

[0185] Sustained-release preparations can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.

[0186] ELISA Assay

[0187] 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.

[0188] NOVX Recombinant Expression Vectors and Host Cells

[0189] 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.

[0190] 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 sequences(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).

[0191] 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).

[0192] 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.

[0193] 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.

[0194] 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).

[0195] 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.

[0196] 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.).

[0197] 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).

[0198] In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using 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 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.

[0199] 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 -fetoprotein promoter (Campes and Tilghman, 1989, Genes Dev 3: 537-546).

[0200] 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.

[0201] 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.

[0202] 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.

[0203] 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.

[0204] 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).

[0205] A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) NOVX protein. Accordingly, the invention further provides methods for producing NOVX protein using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding NOVX protein has been introduced) in a suitable medium such that NOVX protein is produced. In another embodiment, the method further comprises isolating NOVX protein from the medium or the host cell.

[0206] Transgenic NOVX Animals

[0207] 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

[0208] A transgenic animal of the invention can be created by introducing NOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g. by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human NOVX cDNA sequences, i.e., any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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 4,873,44; 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.

[0209] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of a NOVX gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g. functionally disrupt, the NOVX gene. The NOVX gene can be a human gene (e.g. the cDNA of any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44), but more preferably, is a non-human homologue of a human NOVX gene. For example, a mouse homologue of human NOVX gene of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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).

[0210] 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.

[0211] 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.

[0212] 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.

[0213] 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.

[0214] Pharmaceutical Compositions

[0215] 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.

[0216] 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.

[0217] 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 the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0218] 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.

[0219] 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.

[0220] 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.

[0221] 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.

[0222] 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.

[0223] 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.

[0224] 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.

[0225] 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.

[0226] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0227] Screening and Detection Methods

[0228] 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.

[0229] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

[0230] Screening Assays

[0231] 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.

[0232] 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.

[0233] A “small molecule” as used herein, is meant to refer to a composition that has a molecular eight 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.

[0234] 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. USA, 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.

[0235] 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.).

[0236] 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, herein 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.

[0237] 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.

[0238] Determining the ability or 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.

[0239] 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.

[0240] 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.

[0241] In yet another embodiment, the cell-free assay comprises contacting the NOVX protein or biologically-active portion thereof within 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.

[0242] 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).

[0243] 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.

[0244] 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.

[0245] 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.

[0246] 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 WO94/10300), 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.

[0247] 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.

[0248] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

[0249] Detection Assays

[0250] 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.

[0251] Chromosome Mapping

[0252] Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the NOVX sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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.

[0253] 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.

[0254] 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.

[0255] 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.

[0256] 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).

[0257] 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.

[0258] 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.

[0259] 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.

[0260] Tissue Typing

[0261] 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).

[0262] 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.

[0263] 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).

[0264] Each of the sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers that each yield a noncoding amplified sequence of 100 bases. If coding sequences, such as those of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

[0265] Predictive Medicine

[0266] 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 scene 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.

[0267] 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.)

[0268] Yet another aspect of the invention pertains to monitoring the influence of agents (e.g. drugs, compounds) oil the expression or activity of NOVX in clinical trials.

[0269] These and other agents are described in further detail in the following sections.

[0270] Diagnostic Assays

[0271] An exemplary method for detecting the presence or absence of NOVX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) that encodes NOVX protein such that the presence of NOVX is detected in the biological sample An agent for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to NOVX mRNA or genomic DNA. The nucleic acid probe can be, for example, a full-length NOVX nucleic acid, such as the nucleic acid of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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.

[0272] 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 tern “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 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.

[0273] 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.

[0274] 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.

[0275] 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.

[0276] Prognostic Assays

[0277] 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.

[0278] 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).

[0279] 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.

[0280] 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.

[0281] 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.

[0282] 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.

[0283] 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.

[0284] 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).

[0285] 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 polylacrylamide 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.

[0286] 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.

[0287] 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.

[0288] 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.

[0289] 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.

[0290] 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.

[0291] 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.

[0292] 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.

[0293] Pharmacogenomics

[0294] Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e.g. NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0295] 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.

[0296] 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.

[0297] 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 then 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.

[0298] 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.

[0299] Monitoring of Effects During Clinical Trials

[0300] 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.

[0301] 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.

[0302] 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 lover levels than detected, i.e., to decrease the effectiveness of the agent.

[0303] Methods of Treatment

[0304] The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant NOVX expression or activity. The disorders include but are not limited to e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0305] These methods of treatment will be discussed more fully, below.

[0306] Diseases and Disorders

[0307] 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.

[0308] 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.

[0309] 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).

[0310] Prophylactic Methods

[0311] 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.

[0312] Therapeutic Methods

[0313] 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.

[0314] Stimulation of NOVX activity is desirable in situations in which NOVX is abnormally downregulated and/or in which increased NOVX activity is likely to have a beneficial effect. One example of such a situation is where a subject has a disorder characterized by aberrant cell proliferation and/or differentiation (e.g. cancer or immune associated disorders). Another example of such a situation is where the subject has a gestational disease (e.g., preclampsia).

[0315] Determination of the Biological Effect of the Therapeutic

[0316] 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.

[0317] 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.

[0318] Prophylactic and Therapeutic Uses of the Compositions of the Invention

[0319] The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0320] As an example, a cDNA encoding the NOVX protein of the invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof. By way of non-limiting example, the compositions of the invention will have efficacy for treatment of patients suffering from diseases, disorders, conditions and the like, including but not limited to those listed herein.

[0321] 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.

[0322] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.

EXAMPLES

Example A

Polynucleotide and Polypeptide Sequences, and Homology Data

Example 1

[0323] The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1A.

TABLE 1A
NOV1 Sequnence Analysis
	SEQ ID NO:1	829 bp
NOV1a.	GTCCTTGGAGGCCAGAGGGGACTCTGAGCATCGGAAAGCAGGATGCCTGGTTTGCTTT
CG102071-01
DNA Sequence	TATGTGAACCGACAGAGCTTTACAACATCCTGAATCAGGCCACAAAACTCTCCAGATT
	AACAGACCCCAACTATCTCTGTTTATTGGATGTCCGTTCCAAATGGGAGTATGACGAA
	AGCCATGTGATCACTGCCCTTCGAGTGAAGAAGAAAAATAATGAATATCTTCTCCCGG
	AATCTGTGGACCTGGAGTGTGTGAAGTACTGCGTGGTGTATGATAACAACAGCAGCAC
	CCTGGAGATACTCTTAAAAGATGATGATGATGATTCAGACTCTGATGGTGATGGCAAA
	GGAACTGGATGCATTTCAGCCATACCCCATGAAATCGTGCCAGGGAAGGTCTTCGTT
	GGCAATTTCAGTCAAGCCTGTGACCCCAAGATTCAGAAGGACTTGAAAATCAAAGCCC
	ATGTCAATGTCTCCATGGATACAGGGCCCTTTTTTGCAGGCGATGCTGACAAGCTTCT
	GCACATCCGGATAGAAGATTCCCCCGAACCCCAGATTCTTCCCTTCTTACGCCACATG
	TGTCACTTCATTGGGTATCAGCCGCAGTTGTGCCGCCATCATAGCCTACCTCATGTAT
	AGTAACGAGCAGACCTTGCAGAGGTCCTGGGCCTATGTCAAGAAGTGCAAAAACAACA
	TGTGTCCAAATCGGGGATTGGTGAGCCAGCTGCTGGAATGGGAGAAGACTATCCTTGG
	AGATTCCATCACAAACATCATGGATCCGCTCTACTGATCTTCTCCGAGGCCCACCGAA
	GGGTACTGAAGAGCCTC
	ORf Start: ATG at 43	ORf Stop: IGA at 379
	SEQ ID NO:2	112 aa	MW at 12612.0kD
NOV1a.	MPGLLLCEPTELYNILNQATKLSRLTDPNYLCLLDVRSKWEYDESHVITALRVKKKNN
CG102071-01
Protein Sequence	EYLLPESVDLECVKYCVVYDNNSSTLEILLKDDDDDSDSDGDGKGTGCISAIPH

[0324] Further analysis of the NOV1a protein yielded the following properties shown in Table 1B.

TABLE 1B
Protein Sequence Properties NOV1a
PSort     0.4500 probability located in cytoplasm: 0.3000
analysis: probability located in microbody (peroxisome); 0.1000
          probability located in mitochondrial matrix space:
          0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0325] 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	+190, Date]	Residues	Region	Value
AAY44241	Human cell signalling protein-4-	1..102	102/102 (100%)	1e−55
	Homo sapiens. 313 aa.	1..102	102/102 (100%)
	[WO9958558-A2. 18-NOV-1999]
AAGO1344	Human secreted protein. SEQ ID	1..59	55/59 (93%)	2e−26
	NO:5425-Homo sapiens. 125 aa.	1..59	57/59 (96%)
	[EP1033401-A2.06-SEP-2000]
AAM91270	Human immune/haematopoictic	1..56	54/56 (96%)	1e−25
	antigen SEQ ID NO:18863-Homo	7..62	55/56 (97%)
	sapiens. 123 aa. ]WO200157182-
	A2.09-AUG-2001]
AAY07958	Human secreted protein fragment	71..102	32/32 (100%)	3e−12
	#2 encoded from gene 6-Homo	34..65	32/32 (100%)
	sapiens. 276 aa. [WO9918208-A1.
	15-APR-1999]
AAY68782	Amino acid sequence ot a human	17..112	24/103 (23%)	1.7
	phosphorylation effector PHSP-14-	182..284	46/103 (44%)
	Homo sapiens, 416 aa.
	[WO200006728-A2. 10-FEB-2000]

[0326] In a BLAST search of public sequence datbases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1D.

TABLE 1D
Public BLASTP Results for NOV1a
		NOV1a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9Y6J8	Map kinase phosphatase-like	1 . . . 102	102/102 (100%)	2e−55
	protein MK-STYX - Homo sapiens	1 . . . 102	102/102 (100%)
	(Human). 313 aa.
Q9DAR2	Adult male testis cDNA. RIKEN	1 . . . 98	66/98 (67%)	2e−35
	full-length enriched library.	1 . . . 98	86/98 (87%)
	clone: 1700001J05. full insert
	sequence - Mus musculus (Mouse),
	321 aa.
Q9UBP1	MAP kinase phosphatase-like	46 . . . 112	67/67 (100%)	1e−33
	protein MK-STYX - Homo sapiens	1 . . . 67	67/67 (100%)
	(Human). 67 aa (fragment).
Q9UK07	Map kinase phosphatase-like	46 . . . 102	57/57 (100%)	6e−27
	protein MK-STYX - Homo sapiens	1 . . . 57	57/57 (100%)
	(Human). 221 aa (fragment).
Q8XMD0	Hypothetical protein CPE0759 -	15 . . . 98	27/87 (31%)	0.041
	Clostridium perfringens. 399 aa.	296 . . . 380	46/87 (52%)

[0327] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1E.

TABLE 1E
Domain Analysis of NOV1a
Pfam	NOV1a Match	Identities/	Expect Value
Domain	Region	Similarities
		for the Matched Region

Example 2

[0328] 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	1188 bp
NOV2a.	AGTGATGGCTTGTGGATTCAAGCCTAGGTTTGACAGATCTGGAATGTGTGCTCCTATT
CG112767-01
DNA Sequence	CCTCCGCAGTCTGGCCTGTCTGCTTTCTGTCTTCTTTGCCAGCAATGTCCAGGCACTG
	TAAGGTGGGCCGTTAGCTTCCTGGGTTCAGGTAAATGTCTTCCAGTAACCCCTGCTTC
	CCCTGCTCCCCGACAGGTAAGTTCGAGGATCGGGAAGACCACGTCCCCAAGTTGGAGC
	AAATAAACAGCACGAGGATCCTGAGCAGCCAGAACTTCACCCTCACCAAGAAGGAGCT
	GCTGAGCACAGAGCTGCTGCTCCTGGAGGCCTTCAGCTGGAACCTCTGCCTGCCCACG
	CCTCCCCACTTCCTGGACTACTACCTCTTGGCCTCCGTCAGCCAGAAGGACCACCACT
	GCCACACCTGGCCCACCACCTGCCCCCCGAAGACCAAAGAGTGCCTCAAGGACTATGC
	CCATTACTTCCTAGAGGTCACCCTGCAAGTCGCTGCGGCCTGTGTTGGGGCCTCCAGG
	ATTTGCCTGCAGCTTTCTCCCTACTGGACCAGAGACCTGCAGAGGATCTCAAGCTATT
	CCCTGGAGCACCTCAGCACGTGTATTGAAATCCTGCTGGTGGTGTATGACAACGTCCT
	CAAGGATGCCGTAGCCGTCAAGAGCCAGGCCTTGGCAATGGTGCCCGGCACACCCCCC
	ACCCCCACTCAAGTGCTGTTCCAGCCACCAGCCTACCCGGCCCTCGGCCAGCCAGCGA
	CCACCCTGGCACAGTTCCAGACCCCCGTGCAGGACCTATGCTTGGCCTATCGGGACTC
	CTTGCAGGCCCACCGTTCAGGGAGCCTGCTCTCGGGGAGTACAGGCTCATCCCTCCAC
	ACCCCGTACCAACCGCTGCAGCCCTTGGATATGTGTCCCGTGCCCGTCCCTGCATCCC
	TTAGCATGCATATGGCCATTGCAGCTGAGCCCAGGCACTGCCTCGCCACCACCTATGG
	AAGCAGCTACTTCAGTGGGAGCCACATGTTCCCCACCGGCTGCTTTGACAGATAGGCC
	ACCTCCAGACCTCACGAGGAAGCCTTGGAGATGTGGGCAGAGGAAGAGGACACTGAAG
	AGGAGAGCTCAGCCAAGTGAGGCAGCAGGAGGCCATCCCTGAAGAGCCTTGGAACGTG
	GAGGGTCTGTGCTCCTTTTAAATAAAAC
	ORF Start: ATG at 151	ORF Stop: TAG at 1039
	SEQ ID NO:4	296 aa	MW at 32755.1kD
NOV2a.	MSSSNPCFPCSPTGKFEDREDHVPKLEQINSTRILSSQNFTLTKKELLSTELLLLEAF
CG112767-01
Protein Sequence	SWNLCLPTPAHFLDYYLLASVSQKDHHCHTWPTTCPRKTKECLKEYAHYFLEVTLQVA
	AACVGASRICLQLSPYWTRDLQRISSYSLEHLSTCIETLLVVYDNVLKDAVAVKSQAL
	AMVPGTPPTPTQVLFQPPAYPALGQPATTLAQFQTPVQDLCLAYRDSLQAHRSGSLLS
	GSTGSSLHTPYQPLQPLDMCPVPVPASLSMHMAIAAEPRHCLATTYGSSYFSGSHMFP
	TGCFDR
	SEQ ID NO:5	1015 bp
NOV2b.	GTTAGCTTCCTGGGTTCAGGTAAATGTCTTCCAGTAACCCCTGCTTCCCCTGCTCCCC
CG112767-02
DNA Sequence	GACAGGTAAGTTCGAGGATCGGGAAGACCACGTCCCCAAGTTGGAGCAAATAAACAGC
	ACGAGGATCCTGAGCAGCCAGAACTTCACCCTCACCAAGAAGGAGCTGCTGAGCACAG
	AGCTGCTGCTCCTGGAGGCCTTCAGCTGGAACCTCTGCCTGCCCACGCCTGCCCACTT
	CCTGGACTACTACCTCTTGGCCTCCGTCAGCCAGAAGGACCACCACTGCCACACCTGG
	CCCACCACCTGCCCCCGCAAGACCAAAGAGTGCCTCAAGGAGTATGCCCATTACTTCC
	TAGAGGTCACCCTGCAAGATCACATATTCTACAAATTCCAGCCTTCTGTGGTCGCTGC
	GGCCTGTGTTGGGGCCTCCAGGATTTGCCTGCAGCTTTCTCCCTACTGGACCAGAGAC
	CTGCAGAGGATCTCAAGCTATTCCCTGGACCACCTCAGCACGTGTATTGAAATCCTGC
	TGGTAGTGTATGACAACGTCCTCAAGGATGCCGTAGCCGTCAAGAGCCAGGCCTTGGC
	AATGGTGCCCGGCACACCCCCCACCCCCACTCAAGTGCTGTTCCAGCCACCAGCCTAC
	CCGGCCCTCGGCCAGCCAGCGACCACCCTGGCACAGTTCCAGACCCCCGTGCAGGACC
	TATGCTTGGCCTATCGGGACTCCTTGCAGGCCCACCGTTCAGGGAGCCTGCTCTCGGG
	GAGTACAGGCTCATCCCTCCACACCCCGTACCAACCGCTGCAGCCCTTGGATATGTGT
	CCCGTGCCCGTCCCTGCATCCCTTAGCATGCATATGGCCATTGCAGCTGAGCCCAGGC
	ACTGCCTCGCCACCACCTATGGAAGCAGCTACTTCAGTGGGAGCCACATGTTCCCCAC
	CGGCTGCTTTGACAGATATAGGCCACCTCCAGACCTCACGAGGAAGCCTTGGAGATGTGG
	GCAGAGGAAGAGGACACTGAAGAGGAGAG
	ORF Start: ATG at 24	ORF Stop: TAG at 945
	SEQ ID NO:6	307 aa	MW at 34117.7kD
NOV2b.	MSSSNPCFPCSPTGKFEDREDHVPKLEQINSTRILSSQNFTLTKKELLSTELLLLEAF
CG112767-02
Protein Sequence	SWNLCLPTPAHRLDYYLLASVSQKDHHCHTWRTTCPRKTKECLKEYAHYFLEVTLQDH
	IFYKFQPSVVAAACVGASRICLQLSPYWTRDLQRISSYSLEHLSTCIEILLVVYDNVL
	KDAVAVKSQALAMVPGTPPTPTQVLFQPPAYPALGQPATTLAQFQTPVQDLCLAYRDS
	LQAHRSGSLLSGSTGSSLHTPYQPLQPLDMCPVPVPASLSMHMAIAAEPRHCLATTYG
	SSYFSGSHMFPTGCFDR

[0329] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 2B.

TABLE 2B
Comparison of NOV2a against NOV2b.
Protein	NOV2a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV2b	1 . . . 296	267/307 (86%)
	1 . . . 307	267/307 (86%)

[0330] Further analysis of the NOV2a protein yielded the following properties shown in Table 2C.

TABLE 2C
Protein Sequence Properties NOV2a
PSort     0.6500 probability located in cytoplasm; 0.1000
analysis: probability located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen):
          0.0000 probability located in endoplasmic reticulum
          (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0331] A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2D.

TABLE 2D
Geneseq Results for NOV2a
		NOV2a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAE18955	Human cell cycle protein and	15..296	281/293 (95%)	e−164
	mitosts-associated molecule	59..351	281/293 (95%)
	(CCPMAM-3)-Homo sapiens, 351
	aa.[WO200208255-A2, 31-JAN-
	2002]
AAB95737	Human protein sequence SEQ ID	176..296	121/121 (100%)	2e−68
	NO:18627-Homo sapiens, 121 aa.  1..121	121/121 (1000o)
	[EP1074617-A2.07-FEB-2001]
AAB93306	Human protein sequence SEQ ID	51..296	99/254 (38%)	3e−35
	NO:l2379-Homo sapiens, 242 aa.	2..242	133/254 (51%)
	[EP1074617-A2.07-FEB-2001]
AAB40749	Human OREX 0RF513 polypeptide	15..45	31/31 (100%)	4e−10
	sequence SEQ ID NO:1026-Homo	95..125	31/31 (100%)
	sapiens. 125 aa. [WO200058473-
	A2. 05-OCT-2000]
AAG29317	Arabidopsis thaliana protein	44.161	32/119 (26%)	0.002
	fragment SEQ ID NO: 34860-	61..174	57/119 (47%)
	Arabidopsis thaliana. 209 aa.
	[EP1033405-A2. 06-SEP-2000

[0332] In a BLAST search of public sequence datbases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2E

TABLE 2E
Public BLASTP Results for NOV2a
		NOV2a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9H7W8	CDNA FLJ14166 fis. clone	176 . . . 296	121/121 (100%)	5e−68
	NT2RP1000796 (Hypothetical 12.9	1 . . . 121	121/121 (100%)
	kDa protein) - Homo sapiens
	(Human), 121 aa.
Q96LF7	BA690P14.1 (Novel cyclin	15 . . . 296	118/290 (40%)	2e−46
	(Contains FLJ10895)) - Homo	62 . . . 338	159/290 (54%)
	sapiens (Human). 338 aa
	(fragment).
Q9NV69	CDNA FLJ10895 fis. clone	51 . . . 296	99/254 (38%)	8e−35
	NT2RP4002905 - Homo sapiens	2 . . . 242	133/254 (51%)
	(Human), 242 aa.
Q8T2F2	Hypothetical 81.0 kDa protein -	11 . . . 167	39/175 (22%)	1e−06
	Dictyostelium discoideum (Slime	517 . . . 677	75/175 (42%)
	mold). 694 aa.
P93557	Mitotic cyclin - Sesbania rostrata.	28 . . . 162	40/146 (27%)	2e−06
	445 aa.	283 . . . 409	65/146 (44%)

[0333] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2F.

TABLE 2F
Domain Analysis of NOV2a
		Identities/
	NOV2a Match	Similarities	Expect
Pfam Domain	Region	for the Matched Region	Value
cyclin_C	65 . . . 204	32/166 (19%)	0.01
		94/166 (57%)

Example 3

[0334] 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:7	1534 bp
NOV3a.	AAGCATGGTTAAATCTGGTAGATGGAGAGCTCAGGAAAAGCGGCCATGAGCTTTCAGC
CC112776-01
DNA Sequence	ACAATTAGTCCTCACCCTTAGGGGACACCCTAAGGGAAGATGAGTCCCAGGACTAACC
	AGGGGTGTGGGCATCCCTGTGTTTAAAATTCCAGATGGGCACCACACCTTCCAAACCG
	GACACTCCCTTAGATGTATCCTGAATAACTGGGACAAATTCGACCCTGAAACCTTAAA
	AAAAGAAGCAGCTAATTTTCTTCTGTACCACTGCCTGGCCACAGTATTCCTTACAAAA
	TGGAGAAACTTGGCCCCCTGAGGGATGTATTAATTATAACACCCTTCTACAACTAGCT
	CTTTTCTGTAAGCAGGAAGGTAAATGGAGTGAAGTCCCTTACGTACAGGCTTTCTTTG
	CCCTTCTTGACAATACTGCCCTGTGCCAAGCCTGCGAGCTTTGCCCAAATGACAGAGG
	CCCACAATTACCTCCATATTCAGGGCCTCTTCCCTCAGCCCCACTCTCCTCCTGCACT
	GACTCTCCTCCATCTGGCCTCACTGAAGTGTTAAAGGCAAAATGGAAAGAGAACGTAA
	ACTCCGAGAGCCAGGCACCCGAACTATGTCCCTTACAAACAGTAGGAGGAGAATTTGG
	GCGCATTCACATGCATGCCCCCTTCTCACTCTCAAATTTAAAACAAATAAAGGCAGAT
	TTAGGGAAATTCTTGGATGATCCTGATAACCATATACATGTCCTGCAAGGATTAGAGC
	AGTCCTTTGATCTAACATGGAGAGATATCATGTTACTTCTTGATCAGACCTTAAGTCC
	TACTGAAAAAAAAGCAGCTTTAGCAGCAGCCCAGCAATTTAGGGATCGATGGTACCTT
	GGCCAGGTAAACAATCCATTGATGGCCTTGGAGGAGAGGGAAAAATTGCCCACAGGGG
	AACAGGCAGTCCCCACTGTAAATCCTTATTGGGATACTGACTCAGATCATGGAGATTG
	GAGCCACAGGCATTTGCTAACTTGCATTTTAAAAGGGTTGAGGAAGACTAGGAGAAAG
	CCTATGAACTACTCAATGCTATCCACCATTACCCAGGGAAAAGAAGAAAATCCCTCAG
	CCTTTCTAGAAATGCTGCGGGAGGCTCTAAGAAGGCACACCCCCGTAACTCCGGATTC
	CCTGGAAGGCCAACTTATTCTAAAGGATAAACTTATCACCCTAAGAAGCGGCCGATAT
	TGGGAGAAAACTCCAAAGGTCTGCCTTAGGCCCAGAACAAAGCTTGGAGGCATTATTA
	AACCTGCCAACCTCGTTGTTCTATAACAGGGACCAAGAGGAACAGGCCAAAATGGAAA
	AGCAAGATAAGAGAAAGGCTGCAGCCTTAGTCTTGGCTCTCAGACAGGCAGACCTTGG
	TGGCTCAGAGGGAACCAAAAGAGGAGCAGGCCAATTGCCTAGTAGGGCTTGTTATCAG
	TGCGGTTTGCAAGGACACTTTAAAAAAGATTGTCCAACTAGAAACAAACTGCCCCCTC
	GCCCATGTCCAATATGCCAAGGCAAT
	ORF Start: ATG at 151	ORF Stop: TAA at 1300
	SEQ ID NO:8	383 aa	MW at 43317.3kD
NOV3a.	MGTTPSKPDTPLRCILNNWDKFDPETLKKKQLIFFCTTAWPQYSLQNGETWPPEGCIN
CG112776-01
Protein Sequence	YNTLLQLALFCKQEGKWSEVPYVQAFFALLDNTALCQACELCPNDRGPQLPPYSGPLP
	SAPLSSCTDSPPSGLTEVLKAKWKENVNSESQAPELCPLQTVGGEFGRIHMHAPFSLS
	NLKQIKADLGKFLDDPDNHIHVLQGLEQSPDLTWRDIMLLLDQTLSPTEKKAALAAAQ
	QFRDRWYLGQVNNPLMALEEREKLPTGEQAVPTVNPYWDTDSDHGDWSHRHLLTCILK
	GLRKTRRKPMNYSMLSTITQGKEENPSAFLEMLREALRRHTPVTPDSLEGQLILKDKL
	ITLRSGRYWEKTPKVCLRPRTKLGGIIKPANLVVL

[0335] Further analysis of the NOV3a protein yielded the following properties shown in Table 3B.

TABLE 3B
Protein Sequence Properties NOV3a
PSort     0.3000 probability located in nucleus: 0.1000
analysis: probability located in mitochondrial matrix space: 0.1000
          probability located in lysosome (lumen): 0.0000
          probability located in encloplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0336] 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
AAB07704	Protein encoded by the endogenetic	1 . . . 350	227/354 (64%)	e−131
	fragment of HERV-W - Homo	1 . . . 349	274/354 (77%)
	sapiens. 363 aa. [WO200043521-
	A2, 27 Jul. 2000]
AAB07702	Protein encoded by the endogenetic	1 . . . 350	227/354 (64%)	e−131
	fragment of HERV-W - Homo	34 . . . 382	274/354 (77%)
	sapiens. 409 aa. [WO200043521-
	A2, 27 Jul. 2000]
AAB07703	Protein encoded by the endogenetic	1 . . . 350	227/358 (63%)	e−128
	fragment of HERV-W - Homo	14 . . . 366	274/358 (76%)
	sapiens, 393 aa. [WO200043521-
	A2. 27 Jul. 2000]
AAB08194	Amino acid sequence of the MSRV-	1 . . . 350	223/354 (62%)	e−126
	1 RU5 region and gag region -	1 . . . 349	271/354 (75%)
	Multiple Sclerosis retrovirus 1. 484
	aa. [WO200047745-A1. 17 Aug.
	2000]
AAW99558	Protein encoded by pET21C-clone 2	12 . . . 350	219/343 (63%)	e−124
	from MSRV-1 - Multiple sclerosis	14 . . . 351	266/343 (76%)
	related virus type 1. 378 aa.
	[FR2765588-A1. 08 Jan. 1999]

[0337] In a BLAST search of public sequence datbases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 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
Q9NRZ4	Gag - Homo sapiens (Human), 363	1 . . . 350	227/354 (64%)	e−131
	aa.	1 . . . 349	274/354 (77%)
Q9PZ44	Gag polyprotein - multiple	12 . . . 350	219/343 (63%)	e−123
	sclerosis associated retrovirus	1 . . . 338	266/343 (76%)
	element. 352 aa (fragment).
Q9PZ45	Gag polyprotein - multiple	1 . . . 136	78/136 (57%)	3e−39
	sclerosis associated retrovirus	1 . . . 135	91/136 (66%)
	element. 137 aa (fragment).
Q9BRM8	Hypothetical 14.1 kDa protein -	1 . . . 87	60/87 (68%)	5e−33
	Homo sapiens (Human), 123 aa.	1 . . . 87	74/87 (84%)
O36448	Gag - Fowlpox virus (FPV), 499	10 . . . 363	102/412 (24%)	3e−18
	aa.	11 . . . 402	163/412 (38%)

[0338] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3E.

TABLE 3E
Domain Analysis of NOV3a
		Identities/
Pfam	NOV3a Match	Similarities
Domain	Region	for the Matched Region	Expect Value
Gag_p30	260 . . . 337	32/78 (41%)	1.3e−12
		45/78 (58%)

Example 4

[0339] 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:9	1287 bp
NOV4a.	GCCCTGATGGAGCACCTTGTTCCCACGGTGGACTATTACCCCGATAGGACGTACATCT
CG122759-01
DNA Sequence	TCACCTTTCTCCTGAGCTCCCGGGTCTTTATGCCCCCTCATGACCTGCTGGCCCGCGT
	GGGGCAGATCTGCGTGGAGCAGAAGCAGCAGCTGGGAACCGGGCCTGAAAAGCAGGCC
	AAGCTGAAGTCTTTCTCAGCCAAGATCGTGCAGCTCCTGAAGGAGTGGACCGAGGCCT
	TCCCCTATGACTTCCAGGATGAGAAGGCCATGGCCGAGCTGAAAGCCATCACACACCG
	TGTCACCCAGTGTGATGAGGAGAATGGCACAGTGAAGAAGGCCATTGCCCAGATGACA
	CAGAGCCTGTTGCTCTCCTTGGCTGCCCCGAGCCAGCTCCAGGAACTGCGAGAGAAGC
	TCCGGCCACCGGCTGTAGACAAGGGGCCCATCCTCAAGACCAAGCCACCAGCCGCCCA
	GAAGGACATCCTGGGCGTGTGCTGCGACCCCCTGGTGCTGGCCCAGCAGCTGACTCAC
	ATTGAGCTGGACAGGGTCAGCAGCATTTACCCTGAGGACTTGATGCAGATCGTCAGCC
	ACATGGACTCCTTGGACAACCACAGGTGCCGAGGGGACCTGACCAAGACCTACAGCCT
	GGAGGCCTATGACAACTGGTTCAACTGCCTGAGCATGCTGGTGGCCACTGAGGTGTGC
	CGGGTAGTGAAGAAGAAACACCGGACCCGCATGTTGGAGTTCTTCATTGATGTGGCCC
	GGGAGTGCTTCAACATCGGGAACTTCAACTCCATGATGGCCATCATCGCAGCTGGCAT
	GAACCTCAGTCCTGTGGCAAGGCTGAAGAAAACTTGGTCCAAGGTCAAGACACCCAAG
	TTTGATGTCTTGGAGCATCACATGGACCCGTCCAGCAACTTCTGCAACTACCGTACAG
	CCCTGCAGGGGGCCACGCAGAGGTCCCAGATGGCCAACAGCAGCCGTGAAAAGATCGT
	CATCCCTGTGTTCAACCTCTTCGTTAAGGACATCTACTTCCTGCACAAAATCCATACC
	AACCACCTGCCCAACGGGCACATTAACTTTAAGCAGAAATTCTGGGAGATCTCCAGAC
	AGATCCATGAGTTCATGACATGGACACAGGTAGAGTGTCCTTTCGAGAAGGACAAGAA
	GATTCAGAGTTACCTGCTCACGGCGCCCATCTACAGCGAGGAAGCTCTCTTCGTCGCC
	TCCTTTGAAAGTGAGGGTCCCGAGAACCACATGGAAAAAGACAGCTGGAAGACCCTCA
	GGTAGGACGGC
	ORF Start: ATG at 7	ORF Stop: TAG at 1279
	SEQ ID NO:10	424 aa	MW at 48967.1kD
NOV4a.	MEHLVPTVDYYPDRTYIFTFLLSSRVFMPPHDLLARVGQICVEQKQQLEAGPEKQAKL
CG122759-01
Protein Sequence	KSFSAKIVQLLKEWTEAFPYDFQDEKAMAELKAITHRVTQCDEENGTVKKAIAQMTQS
	LLLSLAARSQLQELREKLRPPAVDKGPILKTKPPAAQKDILGVCCDPLVLAQQLTHIE
	LDRVSSIYPEDLMQIVSHMDSLDNHRCRGDLTKTYSLEAYDNWFNCLSMLVATEVCRV
	VKKKHRTRMLEFFIDVARECFNIGNFNSMMAIIAAGMNLSPVARLKKTWSKVKTAKFD
	VLEHHMDPSSNFCNYRTALQGATQRSQMANSSREKIVIPVFNLFVKDIYFLHKIHTNH
	LPNGHTNFKQKFWEISRQIHEFMTWTQVECPFEKDKKIQSYLLTAPIYSEEALFVASF
	ESEGPENHMEKDSWKTLR
	SEQ ID NO:11	1269 bp
NOV4b.	CTGATGGAGCACCTTGTTCCCACGGTGGACTATTACCCCGATAGGACGTACATCTTCA
CG122759-02
DNA Sequence	CCTTTCTCCTGAGCTCCCGGGTCTTTATGCCCCCTCATGACCTGCTGGCCCGCGTGGG
	GCAGATCTGCGTGGAGCAGAAGCAGCAGCTGGAAGCCGGGCCTGAAAAGGCCAAGCTG
	AAGTCTTTCTCAGCCAAGATCGTGCAGCTCCTGAAGGAGTGGACCGAGGCCTTCCCCT
	ATGACTTCCAGGATGAGAAGGCCATGGCCGAGCTGAAAGCCATCACACACCGTGTCAC
	CCAGTGTGATGAGGAGAATGGCACAGTGAGGAAGGCCATTGCCCAGATGACACAGAGC
	CTCTTGCTGTCCTTGGCTGCCCGGAGCCAGCTCCAGGAACTGCGAGAGAAGCTCCGGC
	CACCGGCTGTAGACAAGGGGCCCATCCTCAAGACCAAGCCACCAGCCGCCCAGAAGGA
	CATCCTGGGCGTGTGCTGCGACCCCCTGGTGCTGGCCCAGCAGCTGACTCACATTGAG
	CTGGACAGGGTCAGCAGCATTTACCCTGAGGACTTGATGCAGATCGTCAGCCACATGG
	ACTCCTTGGACAACCACAGGTGCCGAGGGGACCTGACCAAGACCTACAGCCTGGAGGC
	CTATGACAACTGGTTCAACTGCCTGAGCATGCAGGTGGCCACTGAGGTGTGCCGGGTG
	GTGAAGAAGAAACACCGGGCCCGCATGTTGGAGTTCTTCATTGATGTGGCCCGGGAGT
	GCTTCAACATCGGGAACTTCAACTCCATGATGGCCATCATCTCTGGCATGAACCTCAG
	TCCTGTGGCAAGGCTGAAGAAAACTTGGTCCAAGGTCAAGACAGCCAAGTTTGATGTC
	TTGGAGCATCACATGGACCCGTCCAGCAACTTCTGCAACTACCGTACAGCCCTGCAGG
	GGGCCACGCAGAGGTCCCAGATGGCCAACAGCAGCCGTGAAAAGATCGTCATCCCTGT
	GTTCAACCCCTTCGTTAAGGACATCTACTTCCTGCACAAAATCCATACCAACCACCTG
	CCCAACGGGCACATTAACTTTAAGAAATTCTGGGAGATCTCCAGACAGATCCATGAGT
	TCATGACATGGACACAGGTAGAGTGTCCTTTCGAGAAGGACAAGAAGATTCAGAGTTA
	CCTGCTCACGGCGCCCATCTACAGCGAGGAAGCTCTCTTCGTCGCCTCCTTTGAAAGT
	GAGGGTCCCGAGAACCACATGGAAAAAGACAGCTGGAAGACCCTCAGGTAG
	ORF Start: ATG at 4	ORF Stop: TAG at 1267
	SEQ ID NO:12	421 aa	MW at 48652.7kD
NOV4b.	MEHLVPTVDYYPDRTYIFTFLLSSRVFMPPHDLLARVGQICVEQKQQLEAGPEKAKLK
CG122759-02
Protein Sequence	SFSAKIVQLLKEWTEAFPYDFQDEKAMAELKAITHRVTQCDEENGTVRKAIAQMTQSL
	LLSLAARSQLQELREKLRPPAVDKGPILKTKPPAAQKDILGVCCDRLVLAQQLTHIEL
	DRVSSIYPEDLMQIVSHMDSLDNHRCRGDLTKTYSLEAYDNWFNCLSMQVATEVCRVV
	KKKHRARMLEFFIDVARECFNIGNFNSMMAIISGMNLSPVARLKKTWSKVKTAKFDVL
	EHHMDPSSNFCNYRTALQGATQRSQMANSSREKIVIPVFNPFVKDIYFLHKIHTNHLP
	NGHINFKKFWEISRQIHEFMTWTQVECPFEKDKKIQSYLLTAPIYSEEALFVASFESE
	GPENHMEKDSWKTLR

[0340] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 4B.

TABLE 4B
Comparison of NOV4a against NOV4b.
Protein	NOV4a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV4b	1 . . . 424	400/424 (94%)
	1 . . . 421	402/424 (94%)

[0341] Further analysis of the NOV4a protein yielded the following properties shown in Table 4C.

TABLE 4C
Protein Sequence Properties NOV4a
PSort     0.6000 probability located in nucleus; 0.3735
analysis: probability located in microbody (peroxisome); 0.1000
          probability located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0342] A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4D.

TABLE 4D
Geneseq Results for NOV4a
		NOV4a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
ABB04984	Human new ras guanine-nucleotide-	1..424	259/425 (60%)	e−151
	exchange factor 1 SEQ ID NO:2-	47..466	333/425 (77%)
	Homo sapiens. 473 aa.
	[WO200185934-A1.15-NOV-2001]
AAG67823	Human guanine-nucleotide releasing	1..424	258/425 (60%)	e−150
	factor 52 protein-Homo sapiens,	47..465	331/425 (77%)
472 aa.[CN1297910-A. 06-JUN-
2001]
AAB68566	Human GTP-binding associated	1..424	239/426 (56%)	e−131
	protein #66-Homo sapiens. 466 aa.	47..459	309/426 (72%)
	[WO200105970-A2.25-JAN-2001]
AAU28253	Novel human secretory protein. Seq	194..424	213/232 (91%)	e−120
	ID No 610-Homo sapiens. 237 aa.	1..230	218/232 (93%)
	[WO200166689-A2. 13-SEP-2001]
ABG23436	Novel human diagnostic protein	201..424	206/242 (85%)	e−112
	#23427-Homo sapiens. 261 aa.	15..254	211/242 (87%)
	[WO200175067-A2. 11-OCT-2001]

[0343] In a BLAST search of public sequence datbases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4E

TABLE 4E
Public BLASTP Results for NOV4a
		NOV4a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q8TBF1	Similar to RIKEN cDNA	1 . . . 424	419/424 (98%)	0.0
	6330404M18 gene - Homo sapiens	1 . . . 421	421/424 (98%)
	(Human). 428 aa.
Q9D3B6	6330404M18Rik protein - Mus	1 . . . 424	398/424 (93%)	0.0
	musculus (Mouse). 428 aa.	1 . . . 421	410/424 (95%)
Q96MY8	CDNA FLJ31695 fis. clone	1 . . . 424	259/425 (60%)	e−151
	NT2RI2005811. weakly similar to	47 . . . 466	333/425 (77%)
	cell division control protein 25 -
	Homo sapiens (Human). 473 aa.
Q95KH6	Hypothetical 52.9 kDa protein -	1 . . . 424	241/426 (56%)	e−132
	Macaca fascicularis (Crab eating	47 . . . 459	312/426 (72%)
	macaque) (Cynomolgus monkey),
	466 aa.
Q9D300	9130006A14Rik protein - Mus	1 . . . 424	235/425 (55%)	e−129
	musculus (Mouse). 466 aa.	47 . . . 459	309/425 (72%)

[0344] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4F.

TABLE 4F
Domain Analysis of NOV4a
		Identities/
Pfam	NOV4a Match	Similarities
Domain	Region	for the Matched Region	Expect Value
RasGEF	159 . . . 362	61/236 (26%)	1.5e−11
		136/236 (58%)

Example 5

[0345] 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:13	1259 bp
NOV5a.	TGGCCATGGCGTCCCCGGCCATCGGGCAGCGCCCGTACCCGCTACTATTGGACCCCGA
CG124599-01
DNA Sequence	GCCGCCGCGCTATCTACAGAGCCTGAGCGGCCCCGAGCTACCGCCGCCGCCCCCCGAC
	CGGTCCTCGCGCCTCTGTGTCCCGGCGCCCCTCTCCACTGCGCCCGGGGCGCGCGAGG
	GGCGCAGCGCCCGGAGGGCTGCCCGGGGGAACCTGGAGCCCCCGCCCCGGGCCTCCCG
	ACCCGCTCGCCCGCTCCGGCCTGGTCTGCAGCAGAGACTGCGGCGGCGGCCTGGAGCG
	CCCCGACCCCGCGACGTGCGGAGCATCTTCGAGCAGCCGCAGGATCCCAGAGTCCCGG
	CGGAGCGAGGCGAGGGGCACTGCTTCGCCGAGTTGGTGCTGCCCGGCGGCCCCGGCTG
	GTGTGACCTGTGCCGACGAGAGGTGCTGCGGCAGGCGCTGCGCTGCACTGACTGTAAA
	TTCACCTGTCACCCAGAATGCCGCAGCCTGATCCAGTTGGACTGCAGTCAGCAGGAGG
	GTTTATCCCGGGACAGACCCTCTCCAGAAAGCACCCTCACCGTGAGCTTCAGCCAGAA
	TGTCTGTAAACCTGTGGAGGAGACACAGCGCCCGCCCACACTGCAGGAGATCAAGCAG
	AAGATCGACAGCTACAACACGCGAGAGAAGAACTGCCTGGGCATGAAACTGAGTGAAG
	ACGGCACCTACACGGGTTTCATCAAAGTGCATCTGAAACTCCGGCGGCCTGTGACGGT
	GCCTGCTGGGATCCGGCCCCAGTCCATCTATGATGCCATCAAGGAGGTGAACCTGGCG
	GCTACCACGGACAAGCGGACATCCTTCTACCTGCCCCTAGATGCCATCAAGCAGCTGC
	ACATCAGCAGCACCACCACCGTCAGTGAGGTCATCCAGGGGCTGCTCAAGAAGTTCAT
	GGTTGTGGACAATCCCCAGAAGTTTGCACTTTTTAAGCGCATACACAAGGACGGACAA
	GTGCTCTTCCAGAAACTCTCCATTGCTGACCGCCCCCTCTACCTGCGCCTGCTTGCTG
	GGCCTGACACGGAGGTCCTCAGCTTTGTCCTAAAGGAGAATGAAACTGGAGAGGTAGA
	GTGGGATGCCTTCTCCATCCCTGAACTTCAGAACTTCCTAACAATCCTGGAAAAAGAG
	GAGCAGGACAAAATCCAACAAGTGCAAAAGAAGTATGACAAGTTTAGGCAGAAACTGG
	AGGAGGCCTTAAGAGAATCCCAGGGCAAACCTGGGTAACCG
	ORF Start: ATG at 6	ORF Stop: TAA at 1254
	SEQ ID NO:14	416 aa	MW at 46888.2kD
NOV5a.	MASPAIGQRPYPLLLDPEPPRYLQSLSGPELPPPPPDRSSRLCVPAPLSTAPGAREGR
CG124599-01
Protein Sequence	SARRAARGNLEPPPRASRPARPLRPGLQQRLRRRPGAPRPRDVRSIFEQPQDPRVPAE
	RGEGHCFAELVLPGGPGWCDLCGREVLRQALRCTDCKFTCHPECRSLIQLDCSQQEGL
	SRDRPSPESTLTVTFSQNVCKPVEETQRPPTLQEIKQKIDSYNTREKNCLGMKLSEDG
	TYTGFIKVHLKLRRPVTVPAGIRPQSIYDAIKEVNLAATTDKRTSFYLPLDAIKQLHI
	SSTTTVSEVIQGLLKKFMVVDNPQKFALFKRIHKDGQVLFQKLSIADRPLYLRLLAGP
	DTEVLSFVLKENETGEVEWDAFSIPELQNFLTILEKEEQDKIQQVQKKYDKFRQKLEE
	ALRESQGKPG

[0346] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B.

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

[0347] 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
AAY05724	Ras binding protein PRE 1-Mus	1..416	348/416 (83%)	0.0
	musculus. 413 aa. [WO9916784-	1..413	363/416 (86%)
	A1. 08-APR-1999]
AAY94451	Human inflammation associated	190..416	225/227 (99%)	e−126
	protein #8-Homo sapiens. 263 aa.	39..265	227/227 (99%)
	WO200029574-A2. 25-MAY-
	2000]
AAG02604	Human secreted protein. SEQ ID	190..233	42/44 (95%)	1e−17
	NO:6685-Homo sapiens. 83 aa.	39..82	43/44 (97%)
	[EP1033401-A2. 06-SEP-2000]
AAO05504	Human polypeptide SEQ ID NO	288..342	34/55 (61%)	2e−11
	19396-Homo sapiens. 84 aa.	28..82	42/55 (75%)
	[WO200164835-A2. 07-SEP-2001]
AAM41428	Human polypeptide SEQ ID NO	275..406	43/143 (30%)	1e−08
	6359-Homo sapiens. 329 aa.	185..324	76/143 (53%)
	(WO200153312-A1. 26-JUL-2001]

[0348] In a BLAST search of public sequence datbases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP date 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
Q8WWW0	Putative tumor suppressor RASSF3	1 . . . 416	415/416 (99%)	0.0
	isoform A - Homo sapiens (Human).	3 . . . 418	416/416 (99%)
	418 aa.
Q9BT99	Similar to protein interacting with	1 . . . 380	378/380 (99%)	0.0
	guanine nucleotide exchange factor	1 . . . 380	380/380 (99%)
	(Hypothetical 43.9 kDa protein) -
	Homo sapiens (Human). 390 aa.
O35141	Maxp1 - Rattus norvegicus (Rat).	1 . . . 416	361/416 (86%)	0.0
	413 aa.	1 . . . 413	380/416 (90%)
O70407	Putative ras effector Nore1 - Mus	1 . . . 416	348/416 (83%)	0.0
	musculus (Mouse). 413 aa.	1 . . . 413	363/416 (86%)
Q8WWV9	Putative tumor suppressor RASSF3	1 . . . 328	327/328 (99%)	0.0
	isoform B - Homo sapiens (Human).	3 . . . 330	328/328 (99%)
	336 aa.

[0349] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5E.

TABLE 5E
Domain Analysis of NOV5a
		Identities/
	NOV5a Match	Similarities	Expect
Pfam Domain	Region	for the Matched Region	Value
DAG_PE-bind	121 . . . 168	14/51 (27%)	0.00015
		32/51 (63%)
DC1	133 . . . 169	9/48 (19%)	0.54
		25/48 (52%)
PHD	134 . . . 197	10/67 (15%)	0.6
		41/67 (61%)
RA	270 . . . 362	31/114 (27%)	7.3e−28
		86/114 (75%)

Example 6

[0350] 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:15	1293 bp
NOV6a.	CTTGCCTGCCTGCCATGGCCGACAAGGAAGCAGCCTTTGACGACGCAGTGGAAGAACG
CG125142-01
DNA Sequence	AGTGATCAACGAGGAGTACAAAAATGGAAAAAGAACACCCCTTTTCTTTATGATTTG
	GTGTTGACCCATGCTCTGGAGTGGCCCAGCCTAACTGCCCAGTGGCTTCCAGATGTAA
	CCAGACCAGAAGGGAAAGATTTCAGCATTCATCAACTTGTCCTGGGGACATGCACATT
	GGATGAACAAAACCATCTCGTTATAGCCAGTGTGCAACTCCCTAATGATGACACTCAG
	TTTGATGCGTCACACTACAACACTGAGAAAGGAGAATTTGGAGGTTTTTATTCAGTTA
	GAGGAAAAATTGAAATAGAAATCAACATCAACCATGAAGGAGAAGTGAACAAGGTCCG
	TTATATGCCCCAGAACCCTTGTATCATCTCAACTAAGACTCCTTCCAGTCATGTTCTT
	GTCTTTGACTATACAAAACACCCTTCTAAACCAGATCCTTCTGGAGAGTGCAATCCAG
	ACTTGTGTCTCTGTGGACATCAGAAGGAAGGCTATGGGCTTTCTTGGAACCCAAATCT
	CTGTGGGCACTTACTTGGTGCTTCAGATGACCACACCAGCTGCCTGTGGGACAGCAGT
	GCTGTCCCAAAGGAGGGAAAAGTGGTGGATGTGAAGATCATCTTTACAGGGCATACAG
	CAGTAGTAGAAGATGTTTCCTGGCATCTGCTCCATGAGTCTCTGTTTGGGTCAGTTGC
	TGATGATCAGAAACTTATGATTTGGGATACTTGTTCAAACAGTGCTTCCAAACCAAGC
	CATTCAGTTGACGCTCACACTGCTGAAGTGTGCCTCTCTTTCAATCCTTATAGTGAGT
	TCATTCTTGCCACAGGATCCGCTGACAAGACTGTTGCCTTGCGGGATCTGAGAAATCT
	GAAACTTAAGTTGCATTCCTTTGAATTACTTAAGGATAAAATATTCCAGGTTCAGTGG
	TCACCTCACAATGAGACTATTTTGGCTTCCAGTGGTACCAATCACAGACTGAATGTCT
	GGGATTTAAGTAAAATTGGAGAGAAACAATCCCCAGAAGATAAAAAAGACAGGCCACC
	AGAGTTATTGTTTATTCATGGTGGTCACACTGCCAAGATACCTGATTTCTCCGGGAAT
	CCCAACGAACCTTGGGTGATTTGTTCTGTACCAGAACACAATATTATGCAAGTGTGGC
	AAATGGCAGAGAACATTTACAACAATGAAGACCCTGAAGGAAGCGTGGATCCAGAAGG
	ACAAGAGTCCTAGATAT
	ORF Start: ATG at 15	ORF Stop: TAG at 1287
	SEQ ID NO:16	424 aa	MW at 47547.6kD
NOV6a.	MADKEAAFDDAVEERVINEEYKKWKKNTPFLYDLVLTHALEWPSLTAQWLPDVTRPEG
CG125142-01
Protein Sequence	KDFSIHQLVLGTCTLDEQNHLVIASVQLPNDDTQFDASHYNTEKGEFGGFYSVRGKIE
	IEININHEGEVNKVRYMPQNPCIISTKTPSSDVLVFDYTKHPSKPDPSGECNPDLCLC
	GHQKEGYGLSWNPNLCGHLLGASDDHTSCLWDSSAVPKEGKVVDVKIIFTGHTAVVED
	VSWHLLHESLFGSVADDQKLMIWDTCSNSASKPSHSVDAHTAEVCLSFNPYSEFILAT
	GSADKTVALRDLRNLKLKLHSFELLKDKIFQVQWSPHNETILASSGTNHRLNVWDLSK
	IGEKQSPEDKKDRPPELLFIHGGHTAKIPDFSGNPNEPWVICSVPEDNIMQVWQMAEN
	IYNNEDPEGSVDPEGQES

[0351] Further analysis of the NOV6a protein yielded the following properties shown in Table 6B.

TABLE 6B
Protein Sequence Properties NOV6a
PSort     0.4500 probability located in cytoplasm: 0.1131
analysis: probability located in microbody (peroxisome). 0.1000
          probability located in mitochondrial matrix
          space; 0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0352] A search of the NOV6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6C.

TABLE 6C
Geneseq Results for NOV6a
		NOV6a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patene	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAU82965	Human homologue of RSA2 protein	1..424	384/425 (90%)	0.0
	target for antifungal compound-	1..425	396/425 (92%)
	Homo sapiens. 425 aa.
	[WO200202055-A2. 10-JAN-2002]
AAG75145	Human colon cancer antigen protein	1..424	384/425 (90%)	0.0
	SEQ ID NO:5909-Homo sapiens.	42..466	396/425 (92%)
	466 aa. WO200122920-A2. 05-
	APR-2001]
AAB43552	Human cancer associated protein	1..424	384/425 (90%)	0.0
	sequence SEQ ID NO:997-Homo	42..466	396/425 (92%)
	sapiens. 466 aa. [WO200055350-
	A1. 21-SEP-2000]
AAR65232	Retinoblastoma binding protein p48	1..424	384/425 (90%)	0.0
	(RbAp48)-Homo sapiens. 425 aa.	1..425	396/425 (92%)
	[WO9505392-A. 23-FEB-1995]
AAR85892	WD-40 domain-contg. human	1..424	384/425 (90%)	0.0
	retinoblastoma binding protein-	1..425	396/425 (92%)
	Homo sapiens. 425 aa.
	[WO9521252-A2. 10-AUG-1995]

[0353] In a BLAST search of public sequence datbases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6D.

TABLE 6D
Public BLASTP Results for NOV6a
		NOV6a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q09028	Chromatin assembly factor 1 subunit C	1 . . . 424	384/425 (90%)	0.0
	(CAF-1 subunit C) (Chromatin	1 . . . 425	396/425 (92%)
	assembly factor 1 p48 subunit) (CAF-I
	48 kDa subunit) (CAF-1p48)
	(Retinoblastoma binding protein p48)
	(Retinoblastoma-binding protein 4)
	(RBBP-4) (MSI1 protein homolog) -
	Homo sapiens (Human), 425 aa.
Q60972	Chromatin assembly factor 1 subunit C	1 . . . 424	383/425 (90%)	0.0
	(CAF-1 subunit C) (Chromatin	1 . . . 425	396/425 (93%)
	assembly factor 1 p48 subunit) (CAF-1
	48 kDa subunit) (CAF-Ip48)
	(Retinoblastoma binding protein p48)
	(Retinoblastoma-binding protein 4)
	(RBBP-4) - Mus musculus (Mouse).
	461 aa.
Q9W715	Chromatin assembly factor 1 p48	1 . . . 424	383/425 (90%)	0.0
	subunit - Gallus gallus (Chicken), 425	1 . . . 425	395/425 (92%)
	aa.
O93377	Retinoblastoma A associated protein -	1 . . . 424	375/425 (88%)	0.0
	Xenopus laevis (African clawed frog).	1 . . . 425	392/425 (92%)
	425 aa.
Q24572	Chromatin assembly factor 1 P55	7 . . . 414	340/409 (83%)	0.0
	subunit (CAF-1 P55 subunit) (DCAF-	11 . . . 419	373/409 (91%)
	1) (Nucleosome remodeling factor 55
	kDa subunit) (NURF-55) - Drosophila
	melanogaster (Fruit fly). 430 aa.

[0354] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6E.

TABLE 6E
Domain Analysis of NOV6a
		Identities/
Pfam	NOV6a Match	Similarities
Domain	Region	for the Matched Region	Expect Value
WD40	169 . . . 206	12/38 (32%)	0.3
		29/38 (76%)
WD40	219 . . . 256	8/38 (21%)	0.38
		28/38 (74%)
WD40	265 . . . 301	15/38 (39%)	0.16
		29/38 (76%)
WD40	308 . . . 345	6/38 (16%)	0.096
		30/38 (79%)

Example 7

[0355] 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: 17	1269 bp
NOV 7a.	ATGGAAGGAGACTTCTCGGTGTGCAGGAACTGTAAAAGACATGTAGTCTCTGCCAACT
CG125414-01
DNA Sequence	TCACCCTCCATGAGGCTTACTGCCTGCGGTTCCTGGTCCTGTGTCCGGAGTGTGAGGA
	GCCTGTCCCCAAGGAAACCATGGAGGAGCACTGCAAGCTTGAGCACCAGCAGGCCAAT
	GAGTGCCAGGAGCGCCCTGTTGAGTGTAAGTTCTGCAAACTGGACATGCAGCTCAGCA
	AGCTGGAGCTCCACGAGTCCTACTGTGGCAGCCGGACAGAGCTCTGCCAAGGCTGTGG
	CCAGTTCATCATGCACCGCATGCTCGCCCAGCACAGAGATGTCTGTCGCAGTGAACAG
	GCCCAGCTCGGGAAAGGGGAAAGAATTTCAGCTCCTGAAAGGGAAATCTACTGTCATT
	ATTGCAACCAAATGATTCCAGAAAATAAGTATTTCCACCATATGGGTAAATGTTGTCC
	AGACTCAGAGTTTAAGAAACACTTTCCTGTTGGAAATCCAGAAATTCTTCCTTCATCT
	CTTCCAACTCAAGCTGCTGAAAATCAAACTTCCACGATGGAGAAAGATGTTCGTCCAA
	AGACAAGAAGTATAAACAGATTTCCTCTTCATTCTGAAAGTTCATCAAAGAAAGCACC
	AAGAAGCAAAAACAAAACCTTGGATCCACTTTTGATGTCAGAGCCCAAGCCCAGGACC
	AGCTCCCCTAGAGGAGATAAAGCAGCCTATGACATTCTGAGGAGATGTTCTCAGTGTG
	GCATCCTGCTTCCCCTGCCGATCCTAAATCAACATCAGGAGAAATGCCGGTGGTTAGC
	TTCATCAAAAAGGAAAACAAGTGAGAAATTTCAGCTAGATTTGGAAAAGGAAAGGTAC
	TACAAATTCAAAAGATTTCACTTTTAACACTGGCATTCCTGCCTACTTGCTGTGGTCG+E,uns
	TCTTGTGAAAGGTGATGGGTTTTATTCGTTGGGCTTTAAAAGAAAAGGTTTGGCAGAA
	CTAAAAACAAAACTCACGTATCATCTCAATAGATACAGAAAAGGCTTTTGATAAAATT
	CAACTTGACTTCATGTTAAAAACCCTCAACAAACCAGGCGTCGAAGGAACATACCTCA
	AAATAATAAGAGCCATCTATGACAAAACCACAGCCAACATCATACTGAATGAGCAAAA
	GCTGGAGCATTACTCTTGAGAAGTAGAACAAGGCACTTCAGTCCTATTCAACATAGTA
	CTGGAAGTCTCGCCACAGCAATCAGGCAAGAGAAAGAAGTAAAAGGCACCC
	ORF Start: ATG at 1	ORF Stop: TAA at 895
	SEQ ID NO:18	298 aa	MW at 34760.6kD
NOV7a.	MEGDFSVCRNCKRHVVSANFTLHEAYCLRFLVLCPECEEPVPKETMEEHCKLEHQQAN
CG125414-01
Protein Sequence	ECQERPVECKFCKLDMQLSKLELHESYCGSRTELCQGCGQFIMHRMLAQHRDVCRSEQ
	AQLGKGERISAPEREIYCHYCNQMIPENKYFHHMCKCCPDSEFKKHFPVGNPEILPSS
	LPSQAAENQTSTMEKDVRPKTRSINRFPLHSESSSKKAPRSKNKTLDPLLMSEPKPRT
	SSPRGDKAAYDILRRCSQCGILLPLPILNQHQEKCRWLASSKRKTSEKFQLDLEKERY
	YKFKRFHF
	SEQ ID NO: 19	977 bp
NOV 7b.	ATCGCCCTTATGGAAGGAGACTTCTCGGTGTGCAGGAACTGTAAAAGACATGTAGTCT
CG125414-02
DNA Sequence	CTGCCAACTTCACCCTCCATGAGGCTTACTGCCTGCGGTTCCTGGTCCTGTGTCCGGA
	GTGTGAGGAGCCCGTCCCCAAGGAAACCATGGAGGAGCACTGCAAGCTTGAGCACCAG
	CAGGTTGGGTGTACGATGTGTCAGCAGAGCATGCAGAAGTCCTCGCTGGAGTTTCATA
	AGGCCAATGAGTGCCAGGAGCGCCCTGTTGAGTGTAAGTTCTGCAAACTGGACATGCA
	GCTCAGCAAGCTGGAGCTCCACGAGTCCTACTGTGGCAGCCGGACAGAGCTCTGCCAA
	GGCTGTGGCCAGTTCATCATGCACCGCATGCTCGCCCAGCACAGAGATGTCTGTCGCA
	GTGAACAGGCCCAGCTCGGGAAGGGGGAAAGAATTTCAGCTCCTGAAAGGGAAATCTA
	CTGTCATTATTGCAACCAAATGATTCCAGAAAATAAGTATTTCCACCATATGGGTAAA
	TGTTGTCCAGACTCAGAGTTTAAGAAACACTTTCCTGTTGGAAATCCAGAAATTCTTC
	CTTCATCTCTTCCAAGTCAAGCTGCTGAAAATCAAACTTCCACGATGGAGAAAGATGT
	TCGTCCAAAGACAAGAAGTATAAACAGATTTCCTCTTCATTCTGAAAGTTCATCAAAG
	AAAGCACCAAGAAGCAAAAACAAAACCTTGGATCCACTTTTGATGTCAGAGCCCAAGC
	CCAGGACCAGCTCCCCTAGAGGAGATAAAGCAGCCTATGACATTCTGAGGAGATGTTC
	TCAGTGTGGCATCCTGCTTCCCCTGCCGATCCTAAATCAACATCAGGAGAAATGCCGG
	TGGTTAGCTTCATCAAAAGGAAAACAAGTGAGAAATTTCAGCTAGATTTGGAAAAGGA
	AAGGTACTACAAATTCAAAAGATTTCACTTTTAACACTGGCATTCCTGC
	ORF Start: ATG at 10	ORF Stop: TAG at 913
	SEQ ID NO: 20	301 aa	MW at 34625.4kD
NOV7b.	MEGDFSVCRNCKRHVVSANFTLHEAYCLRFLVLCPECEEPVPKETMEEHCKLEHQQVG
CG125414-02
Protein Sequence	CTMCQQSMQKSSLEFHKANECQERPVECKFCKLDMQLSKLELHESYCGSRTELCQGCG
	QFIMHRMLAQHRDVCRSEQAQLGKGERISAPEREIYCHYCNQMIPENKYFHHMGKCCP
	DSEFKKHFPVGNPEILPSSLPSQAAENQTSTMEKDVRPKTRSINRFPLHSESSSKKAP
	RSKNKTLDPLLMSEPKPRTSSPRGDKAAYDILRRCSQCCILLPLPILNQHQEKCRWLA
	SSKGKQVRNFS

[0356] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 7B.

TABLE 7B
Comparison of NOV7a against NOV7b.
Protein	NOV7a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV7b	1 . . . 281	276/300 (92%)
	1 . . . 300	276/300 (92%)

[0357] Further analysis of the NOV7a protein yielded the following properties shown in Table 7C.

TABLE 7C
Protein Sequence Properties NOV7a
PSort     0.3600 probability located in mitochondrial matrix
analysis: space: 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:

[0358] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7D.

TABLE 7D
Geneseq Results for NOV7a
		NOV7a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAW81072	Amino acid sequence of the human	1 . . . 298	298/317 (94%)	e−180
	XAF-1 with zinc finger motif -	1 . . . 317	298/317 (94%)
	Homo sapiens, 317 aa. [EP892048-
	A2, 20 Jan. 1999]
AAY58617	Protein regulating gene expression	7 . . . 115	49/127 (38%)	4e−22
	PRGE-10 - Homo sapiens, 582 aa.	12 . . . 138	68/127 (52%)
	[WO9964596-A2, 16 Dec. 1999]
AAW81077	Amino acid sequences of the human	7 . . . 115	49/127 (38%)	4e−22
	XAF-2L - Homo sapiens. 582 aa.	12 . . . 138	68/127 (52%)
	[EP892048-A2. 20 Jan. 1999]
AAW81073	Amino acid sequence of the human	7 . . . 115	49/127 (38%)	4e−22
	XAF-2 with zinc finger motif -	12 . . . 138	68/127 (52%)
	Homo sapiens, 419 aa. [EP892048-
	A2. 20 Jan. 1999]
AAY01364	Human protein with Zn finger-like	7 . . . 115	49/127 (38%)	4e−22
	motif - Homo sapiens. 582 aa.	12 . . . 138	68/127 (52%)
	[WO9909158-A1. 25 Feb. 1999]

[0359] In a BLAST search of public sequence datbases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7E.

TABLE 7E
Public BLASTP Results for NOV7a
		NOV7a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q99982	XIAP associated factor-1 (ZAP-1) -	1 . . . 298	298/317 (94%)	e−179
	Homo sapiens (Human). 317 aa.	1 . . . 317	298/317 (94%)
O14545	FLN29 (FLN29 gene product) -	7 . . . 115	49/127 (38%)	9e−22
	Homo sapiens (Human). 582 aa.	12 . . . 138	68/127 (52%)
Q8S027	Putative PRL1-interacting factor K -	4 . . . 108	43/154 (27%)	6e−10
	Oryza sativa (japonica cultivar-	398 . . . 551	65/154 (41%)
	group), 559 aa.
O23395	Similar to UFD1 protein (UFD1	8 . . . 109	41/152 (26%)	2e−08
	like protein) - Arabidopsis thaliana	620 . . . 770	61/152 (39%)
	(Mouse-ear cress), 778 aa.
Q8W1E7	AT4g15420/d13755w - Arabidopsis	8 . . . 109	41/152 (26%)	2e−08
	thaliana (Mouse-ear cress). 561 aa.	403 . . . 553	61/152 (39%)

[0360] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7F.

TABLE 7F
Domain Analysis of NOV7a
		Identities/
Pfam	NOV7a Match	Similarities
Domain	Region	for the Matched Region	Expect Value
zf-TRAF	23 . . . 80	19/74 (26%)	1.9e−13
		52/74 (70%)
LIM	93 . . . 143	10/61 (16%)	0.86
		31/61 (51%)

Example 8

[0361] 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:21	525 bp
NOV8a.	CGCGTGGCGCCTCTATATTTCCCCGAGAGGTGCGAGGCGGCTGGGCGCACTCGGAGCG
CG127770-01
DNA Sequence	CGATGGGCGACTGGAAGGTCTACATCAGTGCAGTGCTGCGGGACCAGCGCATCGACGA
	CGTGGCCATCGTGGGCCATGCGGACAACAGCTGCGTGTGGGCTTCGCGGCCCGGGGGC
	CTGCTGGCGGCCATCTCGCCGCAGGAGGTGGGCGTGCTCACGGGGCCGGACAGGCACA
	CCTTCCTGCAGGCGGGCCTGAGCGTGGGGGGCCGCCGCTGCTGCGTCATCCGCGACCA
	CCTGCTGGCCGAGGGTGACGGCGTGCTGGACGCACGCACCAAGGGGCTGGACGCGCGC
	GCCGTGTGCGTGGGCCGTGCGCCGCGCGCGCTCCTGGTGCTAATGGGCCGACGCGGCG
	TACATGGGGGCATCCTCAACAAGACGGTGCACGAACTCATACGCGGGCTGCGCATGCA
	GGGCGCCTAGCCGGCCAGCCAGGCCGCCCACTGGTAGCGCGGGCCAAATAAACTGTGA
	CCT
	ORF Start: ATG at 61	ORF Stop: TAG at 472
	SEQ ID NO: 22	137 aa	MW at 14595.8kD
NOV8a.	MGDWKVYISAVLRDQRIDDVAIVGHADNSCVWASRPGGLLAAISPQEVGVLTGPDRHT
CG127770-01
Protein Sequence	FLQAGLSVGGRRCCVIRDHLLAEGDGVLDARTKGLDARAVCVGRAPRALLVLMGRRGV
	HGGILNKTVHELIRGLRMQGA
	SEQ ID NO: 23	465 bp
NOV8b.	ATGGGCGACTGGAAGGTCTACATCAGTGCAGTGCTGCGGGACCAGCGCATCGACGACG
CG127770-02
DNA Sequence	TGGCCATCGTGGGCCATGCGGACAACAGCTGCGTGTGGGCTTCGCGGCCCGGGGGCCT
	GCTGGCGGCCATCTCGCCGCAGGAGGTGGGCGTGCTCACGGGGCCGGACAGGCACACC
	TTCCTGCAGGCGGGCCTGAGCGTGGGGGGCCGCCGCTGCTGCGTCATCCGCGACCACC
	TGCTGGCCGAAGGTGACGGCGTGCTGGACGCACGCACCAAGGGGCTGGACGCGCGCGC
	CGTGTGCGTGGGCCGTGCGCCGCGCGCGCTCCTGGTGCTAATGGGCCGACGCGGCGTA
	CATGGGGGCATCCTCAACAAGACGGTGCACGAACTCATACGCGGGCTGCGCATGCAGG
	GCGCCTAGCCGGCCAGCCAGGCCGCCCACTGGTAGCGCGGGCCAAATAAACTGTGACC
	T
	ORF Start: ATG at I	ORF Stop: TAG at 412
	SEQ ID NO: 24	137 aa	MW at 14595.SkD
NOV8b.	MGDWKVYISAVLRDQRIDDVAIVGHADNSCVWASRPGGLLAAISPQEVGVLTGPDRHT
CG127770-02
Protein Sequence	FLQAGLSVGGRRCCVIRDHLLAEGDGVLDARTKGLDARAVCVGRAPRALLVLMGRRGV
	HGGILNKTVHELIRGLRMQGA

[0362] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 8B.

TABLE 8B
Comparison of NOV8a against NOV8b.
Protein	NOV8a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV8b	1 . . . 137	137/137 (100%)
	1 . . . 137	137/137 (100%)

[0363] Further analysis of the NOV8a protein yielded the following properties shown in Table 8C.

TABLE 8C
Protein Sequence Properties NOV8a
PSort     0.8188 probability located in lysosome (lumen): 0.6500
analysis: probability located in cytoplasm: 0.1000 probability
          located in mitochondrial matrix space: 0.0000
          probability located in endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0364] A search of the NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8D.

TABLE 8D
Geneseq Results for NOV8a
		NOV8a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length ]Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB19713	Rat profilin-3-Rattus rattus. 137 aa.	1..135	119/135 (88%)	4e−65
	[WO200061598-A2. 19-OCT-20001]	1..135	173/135 (90%)
ABB57140	Mouse ischaemic condition related	1..133	60/136 (44%)	3e−27
	protein sequence SEQ ID NO:335-	1..136	84/136 (61%)
	Mus musculus. 140 aa.
	[WO200188188-A2. 22-NOV-2001]
AAG6417l	140 aa. [WO200146413-A1. 28-	1..139	82/139 (58%)	8e−25
	JUN-2001]
AAG01415	Human secreted protein. SEQ ID	1..126	54/129 (41%)	2e−23
	NO:5496-Homo sapiens, 130 aa.	1..129	77/129 (58%)
	[EP1033401-A2. 06-SEP-2000]
ABG12235	Novel human diagnostic protein	7..133	48/127 (37%)	2e−19
	#12226-Homo sapiens. 122 aa.	5..119	79/127 (55%)
	]WO200175067-A2. 11-OCT-2001]

[0365] In a BLAST search of public sequence datbases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8E.

TABLE 8E
Public BLASTP Results for NOV8a
		NOV8a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9DAD6	1700012P12Rik protein (Profilin-	1 . . . 135	121/135 (89%)	3e−66
	III) - Mus musculus (Mouse). 137	1 . . . 135	125/135 (91%)
	aa.
S04067	profilin - mouse. 140 aa.	1 . . . 133	60/136 (44%)	6e−27
		1 . . . 136	84/136 (61%)
P10924	Profilin I - Mus musculus	4 . . . 133	59/133 (44%)	2e−26
	(Mouse). and. 139 aa.	3 . . . 135	83/133 (62%)
A28622	profilin [validated] - human. 140	1 . . . 133	60/136 (44%)	3e−26
	aa.	1 . . . 136	83/136 (60%)
S36804	profilin II - human. 140 aa.	1 . . . 133	59/136 (43%)	1e−25
		1 . . . 136	83/136 (60%)

[0366] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8F.

TABLE 8F
Domain Analysis of NOV8a
		Identities/
Pfam	NOV8a Match	Similarities
Domain	Region	for the Matched Region	Expect Value
Profilin	3 . . . 128	29/135 (21%)	3.2e−12
		86/135 (64%)

Example 9

[0367] 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:25	649 bp
NOV9a.	CCTGGGCATGTGGTATGAGATCAAGGCCCAGGTACACAACATCCACCTGTGCAAAGAC
CG127897-01
DNA Sequence	AAACATGGCAAGACTGGGCTGCAGCTGCAGACCACCAACAAGGGGCTCTTTGTGCAGG
	TCCAGGCCAACACCACTGCATCCCTCATGCTGCTGTGCTTTGGGGACCAAATCCTACA
	GATTGATGGGCATGACTGTGCCAAGTGGAACATGGAAAAAGCCCATGTTATAAGATGG
	GAGTCTGGTGACAAGATTGTTATGGTCATTCAGGACAGGATAGTCCAGTGGATTGTCA
	CCATGCACAAGGACAGCACAAGCCATGGTGGCTTCATCATCAAGAAGGGAAAGGTCTT
	CCCTGTGGTCAAAGGGAGCTCTGGACTCTTCACCAACCACCATGTGTGCCAGGTTCAA
	GAACGTTTAACAAGCACTGTGCAGAGTGTCATTGGGCTGAAAGAGATCTCAGAGATTC
	TGGCCACAGCCAGGAACATTGTCACCCTGATCATCATCCCCACTGTGATCTATGAGCA
	CATAGTCAAAAAGTTTTCCCTGACCCATCGCCACCACATATGGACCACTTCATCCCAG
	ATGCCTGAAGCCACAGGAGGGCAGCTTAGGCCCTCCCACCCTCCTGCAGGAAAGGCCA
	GCCACTCTTGA
	ORF Start: ATG at 8	ORF Stop: TGA at 647
	SEQ ID NO: 26	213 aa	MW at 23880.6kD
NOV9a.	MWYEIKAQVHNIHLCKDKHGKTGLQLQTTNKGLFVQVQANTTASLMLLCFGDQILQID
CG127897-01
Protein Sequence	GHDCAKWNMEKAHVIRWESGDKIVMVIQDRIVQWIVTMHKDSTSHGGFIIKKGKVFPV
	VKGSSCLFTNHHVCQVQERLTSTVQSVIGLKEISEILATARNIVTLIIIPTVIYEHIV
	KKFSLTHRHHIWTTSSQMPEATGGQLRPSHPPAGKASHS

[0368] Further analysis of the NOV9a protein yielded the following properties shown in Table 9B.

TABLE 9B
Protein Sequence Properties NOV9a
PSort     0.5336 probability located in microbody (peroxisome):
analysis: 0.4500 probability located in cytoplasm: 0.2065
          probability located in lysosome (lumen): 0.1000
          probability located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0369] A search of the NOV9a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 9C.

TABLE 9C
Geneseq Results for NOV9a
		NOV9a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAY84610	A human membrane associated	4..195	119/200 (59%)	1e−53
	organizational protein (HJNCT)-	101..292	143/200 (71%)
	Homo sapiens. 292 aa.
	[WO20018915-A2. 06-APR-2000]
ABB89421	Human polypeptide SEQ ID NO	4..195	118/200 (59%)	3e−53
	1797-Homo sapiens. 292 aa.	101..292	143/200 (71%)
	[WO200190304-A2. 29-NOV-2001]
AAU17396	Novel signal transduction pathway	4..195	118/200 (59%)	3e−53
	protein, Seq ID 961-Homo sapiens.	132..323	143/200 (71%)
	323 aa. [WO200154733-A1. 02-
	AUG-2001]
AAB42817	Human ORFX 0RF2581	4..195	118/200 (59%)	3e−53
	polypeptide sequence SEQ ID	16..207	143/200 (71%)
	NO:5162-Homo sapiens 207 aa.
	[WO200058473-A2. 05-OCT-2000]
AAE13846	Human lung tumour-specific protein	4..178	88/183 (48%)	9e−41
	21484-Homo sapiens. 303 aa.	112..288	128/183 (69%)
	[WO200172295-A2. 04-OCT-2001]

[0370] In a BLAST search of public sequence datbases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9D.

TABLE 9D
Public BLASTP Results for NOV9a
		NOV9a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9H190	Syntenin 2 (Syntenin-2) (Syndecan	4 . . . 195	118/200 (59%)	8e−53
	binding protein 2) - Homo sapiens	101 . . . 292	143/200 (71%)
	(Human). 292 aa.
Q99JZO	Syntenin 2 (Syndecan binding	4 . . . 184	115/189 (60%)	1e−51
	protein 2) - Mus musculus	101 . . . 283	137/189 (71%)
	(Mouse). 292 aa.
O08992	Syntenin 1 (Syndecan binding	4 . . . 178	91/183 (49%)	6e−42
	protein I) (Scaffold protein Pbp1) -	108 . . . 284	130/183 (70%)
	Mus musculus (Mouse). 299 aa.
Q9JI92	Syntenin 1 (Syndecan binding	4 . . . 178	90/183 (49%)	2e−41
	protein 1) - Rattus norvegicus	109 . . . 285	129/183 (70%)
	(Rat). 300 aa.
O88601	Syntenin - Mus musculus (Mouse).	4 . . . 178	90/183 (49%)	3e−41
	298 aa.	107 . . . 283	129/183 (70%)

[0371] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9E.

TABLE 9E
Domain Analysis of NOV9a
		Identities/
Pfam	NOV9a Match	Similarities
Domain	Region	for the Matched Region	Expect Value
PDZ	11 . . . 88	57/84 (68%)	0.37

Example 10

[0372] The NOV10 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 10A.

TABLE 10A
NOV10 Sequence Analysis
	SEQ ID NO:27	814 bp
NOV10a.	CTGCCATCGCTATGTCTCTGCAAAAGACCCCTCCGACCCGAGTGTTCGTGGAACTGGT
CG127936-01
DNA Sequence	TCCCTGGGCTGACCGGAGCCGGGAGAACAACCTGGCCTCAGGGAGAGAGACGCTACCG
	GGCTTACGCCACCCCCTCTCCTCAACACAAGCCCAAACTGCTACCCGCGAGGTGCAAG
	TAAGCGGCACCTCAGAAGTGTCTGCGGGCCCTGACCGGGCGCAGGTGGTGGTGCGAGT
	GAGCAGCACCAAGGAGGCGGCAGCCGAGGCCAAAAAGAGCGTTTGTCGCCGTCTAGAT
	TACATCACGCAGAGCCTCCAGCAGCAGGGCTTTCAGGCAGAAAATATAACTGTGACAA
	AGGATTTTAGGAGAGTGGAAAATGCTTATCACATGGAACCAGAGGTATGTATTACATT
	TACTGAATTTGGAAAAATGCAAAATATTTGTAACTTTCTTGTTGAAAAGCTAGATAGC
	TCTGTTGTCATCAGCCCACCCCAGTTCTATCATACTCCACGTTCTGTTGAGAATCTTC
	GGCGGCAAGCCTGTCTTGTTGCTGTTGAGAATGCGTGGCGCAAAGCTCAAGAAGTCTG
	TAACCTTGTTGGCCAAACCTTAGGAAAACCTTTACTAATCAAAGAAGAAGAAACAAAA
	GAATGGGAAGGCCAAATAGATGATCACCAGTCATCCAGACTCTCAAGTTCATTAACTG
	TACAACAAAAAATCAAAAGTGCAACAATACATGCTGCTTCAAAAGTATTTATAACTTT
	TGAGCTAAAGGGAAAAGAGAAGAGAAAAAAGCACCTTTGAAATTCCAAACAAATTATA
	TT
	ORF Start: ATG at 12	ORF Stop: TGA at 792
	SEQ ID NO:28	260 aa	MW at 29153.9kD
NOV10a.	MSLQKTPPTRVFVELVPWADRSRENNLASGRETLPGLRHPLSSTQAQTATREVQVSGT
CG127936-01
Protein Sequence	SEVSAGPDRAQVVVRVSSTKEAAAEAKKSVCRRLDYTTQSLQQQGFQAENITVTKDFR
	RVENAYHMEAEVCITFTEFGKMQNICNFLVEKLDSSVVISPPQFYHTPGSVENLRRQA
	CLVAVENAWRKAQEVCNLVGQTLGKPLLIKEEETKEWEGQIDDHQSSRLSSSLTVQQK
	IKSATIHAASKVFITFEVKGKEKRKKHL
	SEQ ID NO: 29	807 bp
NOV10b.	CCTTATGTCTCTGCAAAAGACCCCTCCGACCCGAGTGTTCGTGGAACTGGTTCCCTGG
CG127936-02
DNA Sequence	GCTGACCGGAGCCGGGAGAACAACCTGGCCTCAGGGAGAGAGACGCTACCGGGCTTAC
	GCCACCCCCTCTCCTCAACACAAGCCCAAACTGCTACCCGCGAGGTGCAAGTAAGCGG
	CACCTCAGAAGTGTCTGCGGGCCCTGACCGGGCGCAGGTGGTGGTGCGAGTGAGCAGC
	ACCAAGGAGGCGGCAGCCGAGGCCAAAAAGAGCGTTTGTCGCCGTCTAGATTACATCA
	CGCAGAGCCTCCAGCAGCAGGGCGTGCAGGCAGAAAATATAACTGTGACAAAGGATTT
	TAGGAGAGTGGAAAATGCTTATCACATGGAAGCAGAGGTCTGCATTACATTTACTGAA
	TTTGGAAAAATGCAAAATATTTGTAACTTTCTTGTTGAAAAGCTAGATAGCTCTGTTG
	TCATCAGCCCACCCCAGTTCTATCATACTCCAGGTTCTGTTGAGAATCTTCGACGGCA
	AGCCTGTCTTGTTGCTGTTGAGAATGCGTGGCGCAAAGCTCAAGAAGTCTGTAACCTT
	GTTGGCCAAACCTTAGGAAAACCTTTACTAATCAAAGAAGAAGAAACAAAAGAATGGG
	AAGGCCAAATAGATGATCACCAGTCATCCAGACTCTCAAGTTCATTAACTGTACAACA
	AAAAATCAAAAGTGCAACAATACATGCTGCTTCAAAAGTATTTATAACTTTTGAGGTA
	AAGGGAAAAGAGAAGAGAAAAAAGCACCTTTGAAATTCCAAACAAATTATATT
	ORF Start: ATG at 5	ORF Stop: TGA at 785
	SEQ ID NO:30	260 aa	MW at 29105.SkD
NOV10b.	MSLQKTPPTRVFVELVPWADRSRENNLASCRETLPGLRHPLSSTQAQTATREVQVSGT
127936-02
Protein Sequence	SEVSAGPDRAQVVVRVSSTKEAAAEAKKSVCRRLDYITQSLQQQCVQAENITVTKDFR
	RVENAYHMEAEVCITFTEFGKMQNICNFLVEKLDSSVVISPPQFYHTPGSVENLRRQA
	CLVAVENAWRKAQEVCNLVGQTLGKPLLIKEEETKEWEGQIDDHQSSRLSSSLTVQQK
	IKSATIHAASKVFITFEVKGKEKRKKHL

[0373] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 10B.

TABLE 10B
Comparison of NOV10a against NOV10b.
Protein	NOV10a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV10b	1 . . . 260	250/260 (96%)
	1 . . . 260	250/260 (96%)

[0374] Further analysis of the NOV10a protein yielded the following properties shown in Table 10C.

TABLE 10C
Protein Sequence Properties NOV10a
PSort     0.6000 probability located in nucleus: 0.3000
analysis: probability located in microbody (peroxisome): 0.1000
          probability located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0375] A search of the NOV10a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10D.

TABLE 10D
Geneseq Results for NOV10a
		NOV10a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB15923	E. coil proliferation associated	53..251	43/209 (20%)	0.010
	protein sequence SEQ ID NO:280-	30..233	91/209 (42%)
	Escherichia coli. 246 aa.
	[WO200044906-A2. 03-AUG-2000]
AAG29759	Arabidopsis thaliana protein	66..158	25/94 (26%)	0.051
	fragment SEQ ID NO:35462-	41..129	51/94 (53%)
	Arabidopsis thaliana. 350 aa.
	[EP1033405-A2. 06-SEP-2000]
AAG29758	Arabidopsis thaliana protein	66..158	25/94 (26%)	0.051
	fragment SEQ ID NO:35461-	62..150	51/94 (53%)
	Arabidopsis thaliana. 371 aa.
	[EP1033405-A2. 06-SEP-2000]
AAB47763	Novel G-protein coupled receptor #3	25..193	41/176 (23%)	3.8
	-Homo sapiens. 848 aa.	209..375	73/176 (41%)
	]WO200181411-A2. 01-NOV-2001]
AAB47761	Novel G-protein coupled receptor #1	25..193	41/176 (23%)	3.8
	-Homo sapiens. 769 aa.	209..375	73/176 (41%)
	[WO200181411-A2. 01-NOV-2001]

[0376] In a BLAST search of public sequence datbases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10E.

TABLE 10E
Public BLASTP Results for NOV10a
		NOV10a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9ESJ7	PLK interacting protein - Mus	1 . . . 260	215/260 (82%)	e−118
	musculus (Mouse). 259 aa.	1 . . . 259	228/260 (87%)
Q9CX27	4921528N06Rik protein - Mus	13 . . . 260	206/248 (83%)	e−113
	musculus (Mouse). 247 aa.	1 . . . 247	219/248 (88%)
Q9JK12	A1P70 protein - Mus musculus	53 . . . 260	186/208 (89%)	e−103
	(Mouse). 208 aa (fragment).	1 . . . 208	196/208 (93%)
Q9CRM0	4921528N06Rik protein - Mus	1 . . . 202	164/202 (81%)	6e−88
	musculus (Mouse). 255 aa	54 . . . 254	174/202 (85%)
	(fragment).
Q9D615	4921528N06Rik protein - Mus	13 . . . 211	145/199 (72%)	4e−73
	musculus (Mouse). 176 aa.	1 . . . 176	153/199 (76%)

[0377] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10F.

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

Example 11

[0378] The NOV11 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11A.

TABLE 11A
NOV11 Sequence Analysis
	SEQ ID NO:31	1335 bp
NOV11a.	AGTCTCCTCTGGAGAAAATAATCTGTGAAATTATGTGAATAGAGACCATTTTTCAAAA
CG127954-01
DNA Sequence	CAATGGGGGAAAGAGCAGGAAGTCCAGGTACTGATCAAGAAAGAAAGGCAGGCAAACA
	CCATTATTCTTACTCATCTGATTTTGAAACGCCACAGTCTTCTGGCCGATCATCGCTG
	GTCAGTTCTTCACCTGCAAGTGTTAGGAGAAAAAATCCTAAAAGACAAACTTCAGATG
	GCCAAGTACATCACCGGAAACCAAGCCCTAAGGGTCTACCAAACAGAAAGGGAGTCCG
	AGTGGGATTTCGCTCCCAGAGCCTCAATAGAGAGCCACTTCGGAAAGATACTGATCTT
	GTTACAAAACGGATTCTGTCTGCAAGACTGCTAAAAATCAATGAGTTGCAGAATGAAG
	TATCTGAACTCCAGGTCAAGTTAGCTGAGCTGCTAAAAGAAAATAAATCTTTGAAAAG
	GCTTCAGTACAGACAGGAGAAAGCCCTGAATAAGTTTGAAGATGCCGAAAATGAAATC
	TCACAACTTATATTTCGTCATAACAATGAGATTACAGCACTCAAAGAACGCTTAAGAA
	AATCTCAAGAGAAAGAACGGGCAACTGAGAAAAGGGTAAAAGATACAGAAAGTGAACT
	ATTTAGGACAAAATTTTCCTTACAGAAACTGAAAGAGATCTCTGAAGCTAGACACCTA
	CCTGAACGAGATGATTTGGCAAAGAAACTAGTTTCAGCAGAGTTAAAGTTAGATGACA
	CCGAGAGAAGAATTAAGGAGCTATCGAAAAACCTTGAACTGAGTACTAACAGTTTCCA
	ACGACAGTTGCTTGCTGAAAGGAAAAGGGCATATGAGGCTCATGATGAAAATAAAGTT
	CTTCAAAAGGAGGTACAGCGACTATATCACAAATTAAAGGAAAAGGAGAGAGAACTGG
	ATATAAAAAATATATATTCTAATCGTCTGCCAAAGTCCTCTCCAAATAAAGAGAAAGA
	ACTTGCATTAAGAAAAAATGCATGCCAGAGTGATTTTGCAGACCTGTGTACAAAAGGA
	GTACAAACCATGGAAGACTTCAAGCCAGAAGAATATCCTTTAACTCCAGAAACAATTA
	TGTGTTACGAAAACAAATGGGAAGAACCAGGACATCTTACTTTGCAATCTCAAAAGCA
	AGACAGGCATGGAGAAGCAGGGATTCTAAACCCAATTATGGAAAGAGAAGAAAAATTT
	GTTACAGATGAAGAACTCCATGTCGTAAAACAGGAGGTTGAAAAGCTGGAGGATGGTA
	AGAAAAAGAGTTTGTTTAAGCATGTGACAAGTCAGCATCCCTTGAGAAAGAAAGAGTG
	A
	ORF Start: ATG at 61	ORF Stop: TGA at 1333
	SEQ ID NO: 32	424 aa	MW at 49547.6kD
NOV11a.	MGERAGSPGTDQERKAGKHHYSYSSDFETPQSSGRSSLVSSSPASVRRKNPKRQTSDG
CG127954-01
Protein Sequence	QVHHRKPSRKGLPNRKGVRVGFRSQSLNREPLRKDTDLVTKRILSARLLKINELQNEV
	SELQVKLAELLKENKSLKRLQYRQEKALNKFEDAENEISQLIFRHNNEITALKERLRK
	SQEKERATEKRVKDTESELFRTKFSLQKLKEISEARHLPERDDLAKKLVSAELKLDDT
	ERRIKELSKNLELSTNSFQRQLLAERKRAYEAHDENKVLQKEVQRLYHKLKEKERELD
	IKNIYSNRLPKSSPNKEKELALRKNACQSDFADLCTKGVQTMEDFKPEEYPLTPETIM
	CYENKWEEPGHLTLQSQKQDRHGEAGILNPIMEREEKFVTDEELHVVKQEVEKLEDGK
	KKSLFKHVTSQHPLRKKE

[0379] Further analysis of the NOV11a protein yielded the following properties shown in Table 11B.

TABLE 11B
Protein Sequence Properties NOV11a
PSort     0.9219 probability located in nucleus; 0.3000 probability
analysis: located in microbody (peroxisome): 0.1000 probability
          located in mitochondrial matrix space: 0.1000 probability
          located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0380] 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/Lemgth	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB11820	Human secreted protein homologue.	95 . . . 400	120/331 (36%)	5e−47
	SEQ ID NO:2190—Homo sapiens.	150 . . . 480	188/331 (56%)
	683 aa. [WO200157188-A2.
	09 AUG 2001]
ABB04337	Human uterine globin 40	332 . . . 404	73/75 (97%)	3e−36
	polypeptide—Homo sapiens, 362 aa.	1 . . . 75	73/75 (97%)
	[CN1313335-A. 19 SEP 2001]
ABB21697	Protein #3696 encoded by probe for	95 . . . 237	61/143 (42%)	3e−28
	measuring heart cell gene	29 . . . 171	102/143 (70%)
	expression—Homo sapiens, 171 aa.
	[WO200157274-A2, 09 AUG 2001]
ABB62559	Drosophila melanogaster	36 . . . 284	62/249 (24%)	4e−20
	polypeptide SEQ ID NO 14469—	21 . . . 261	126/249 (49%)
	Drosophila melanogaster. 599 aa.
	[WO200171042-A2. 27 SEP 2001]
ABB58657	Drosophila melanogaster	36 . . . 424	92/418 (22%)	4e−l2
	polypeptide SEQ ID NO 2763—	1208 . . . 1612	175/418 (41%)
	Drosophila melanogaster. 2274 aa.
	[WO200171042-A2. 27 SEP 2001]

[0381] In a BLAST search of public sequence datbases, the NOV11a protein was found to have homology to the proteins shown in the BLASTP data in Table 11D.

TABLE 11D
Public BLASTP Results for NOV11a
		NOV11a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q95KB2	Hypothetical 50.0 kDa protein -	1 . . . 424	409/430 (95%)	0.0
	Macaca fascicularis (Crab eating	1 . . . 430	415/430 (96%)
	macaque) (Cynomolgus monkey).
	430 aa.
Q9BWX7	BA342L8.1 (novel protein similar	1 . . . 404	403/410 (98%)	0.0
	to C21ORF13) - Homo sapiens	1 . . . 410	403/410 (98%)
	(Human). 697 aa.
Q9D5J9	4930431B11Rik protein - Mus	1 . . . 405	307/413 (74%)	e−168
	musculus (Mouse). 419 aa.	1 . . . 412	354/413 (85%)
O95447	Protein C21orf13 - Homo sapiens	95 . . . 400	120/331 (36%)	1e−46
	(Human). 670 aa.	137 . . . 467	188/331 (56%)
Q9VVD0	CG6652 protein - Drosophila	36 . . . 284	62/249 (24%)	1e−19
	melanogaster (Fruit fly). 599 aa.	21 . . . 261	126/249 (49%)

[0382] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11E.

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

Example 12

[0383] The NOV12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12A.

TABLE 12A
NOV 12 Sequence Analysis
                 SEQ ID NO: 33                 2071 bp
NOV12a.          ACTCTCCTCCCCCGAGCGGCAGCGGCAGCGGCGGCGGCGGCGGCTGCTGCGGGCGCTG
CG128132-01
DNA Sequence     AATGAGAGACGGTGACTGTTCGGGTCGACGAGTGCTACTCTAGGCGGCGGCGGCCGTG
                 GCGGTGAAGCGTGAGGCCGGCATCGTCTTTCCGTCCTCTGAGGCGACGGCCGCGGCTG
                 CACAGGAATAATGTATTTGTGGCCTTGGACATGAGGCAGTCAGTCCTCTGTTGCTGTT
                 CACAGGAATAATGTATTTGTGGCCTTGGACATGAGGCAGTCAGTCCTCTGTTGCTGTT
                 AACATAAGGTCAGGGACTGATGAGGAAAGCATGGACCTAATGAACGGGCAGGCAAGCA
                 GTGTCAATATTGCAGCTACTGCTTCTGAGAAAAGTAGCAGCTCTGAATCCTTAAGTGA
                 CAAAGGCTCTGAATTGAAGAAAAGCTTTGATGCTGTGGTATTCGATGTTCTTAAGGTT
                 ACACCAGAAGAATATGCGGGTCAGATAACATTAATGGATGTTCCAGTATTTAAAGCTA
                 TTCAACCAGATGAGCTTTCAAGTTGTGGATGGAATAAAAAAGAAAAATATAGTTCTGC
                 ACCAAATGCAGTTGCCTTCACAAGAAGATTCAATCATCTAAGCTTTTGGGTTGTTACA
                 CAGATTCTTCATGCTCAAACATTAAAAATTAGAGCAGAAGTTTTGAGCCACTATATTA
                 AAACTGCTAAGAAACTGTATGAGCTGAATAACCTTCATCCACTTATGGCAGTGGTTTC
                 TGGCCTACAGAGTCCCCCAATTTTCAGGTTGACTAAAACATGGGCGTTATTAAGTCGA
                 AAACACAAAACTACCTTTGAAAAATTACAATATGTAATGACTPAACAACATAACTACA
                 AAAGACTCAGAGACTATATAAGTAGCTTAAAGATGACACCTTGCATTCCCTATTTAGG
                 TATCTATTTGTCAGATTTAACATACATCGATTCAGCATACCCATCAACTGGCAGCATT
                 CTAGAAAATGAGCAAAGATCAAATTTAATGAATAATATCCTTCGAATAATTTCTGATT
                 TACAGCAGTCTTGTGAATATGATATTCCCATGTTGCCTCATGTCCAAAAATATCTCAA
                 CTCTGTTCAGTATATAGAAGAACTACAAAAATTTGTGGAAGACGATAATTACAAGCTT
                 TCATTAAAGATAGAACCAGGGACAAGCACCCCACGTTCTGCTGCTTCCAGAGAAGATT
                 TAGTAGGTCCTGAAGTAGGAGCGTCTCCACAGAGTGGACGAAAAAGTGTGGCAGCTGA
                 TAGTAGGTCCTGAAGTAGGAGCGTCTCCACAGAGTGGACGAAAAAGTGTGGCAGCTGA
                 AGGAAGTGCCATAGTTTGCGTTATAATTTCATTCATAAAATGAACACAGCAGPATTTA
                 AGAGTGCAACCTTTCCAAATGCAGGACCAAGACATCTGTTAGATGATAGCGTCATGGA
                 GCCCCATCCGCCATCTCGAGGCCAAGCTGAAAGTTCTACTCTTTCTAGTGGAATATCA
                 ATAGGTAGCAGCGATGGTTCTGAACTAAGTGAAGAGACCTCATGGCCTGCTTTTGAAA
                 GGAACACATTATACCATTCTCTCGGCCCCGTCACAAGAGTCGCACGAAATGGCTATCG
                 AAGTCACATGAAGGCCAGCAGTTCTGCAGAATCAGAAGATTTGGCAGTACATTTATAT
                 CCAGGAGCTGTTACTATTCAAGGTGTTCTCAGGAGAAAAACTTTGTTAAAAGAAGGCA
                 AAAACCCTACAGTAGCATCTTCGACAAAATATTCCGCAGCTTTGTGTGGGACACAGCT
                 TTTTTACTATGCTGCCAAATCTCTAAAGGCTACCGAAAGAAAACATTTCAAATCAACA
                 TCCAATAAGAACGTATCTGTGATAGGATGGATGGTGATGATGGCTGATGACCCTGAAC
                 ATCCTGATCTCTTCCTGCTGACTGACTCTGAGAAAGGAAATTCGTACAAGTTTCAAGC
                 TGGCAATAGAATGAATGCAATGTTATGGTTTAAGCATTTGAGTGCAGCCTGCCAAAGT
                 ACCAAACAACAGGTTCCTACAAACTTGATGACTTTTGAGTAGAAGCCTGAGAAAAAAA
                 GAGAGGTGAACTGTTGCTTCTACGTGACCATGAGGACCTGA
                 ORF Start: ATG at 263         ORF Stop: TAG at 2012
                 SEQ ID NO: 34                 583 aa    MW at 65166.4kD
NOV 12a.         MDLMNGQASSVNIAATASEKSSSSESLSKDGSELKKSFDAVVFDVLKVTPEEYAGQIT
CG12288132-01
Protein Sequence LMDVPVFKAIQRDELSSCCWNKKEKYSSAPNAVAFTRRPNHVSFWVVREILHAQTLKI
                 RAEVLSHYTKTAKKLYELNNLHALMAVVSGLQSAPIPRLTKTWALLSRKDKTTFEKLE
                 YVMSKEDNYKRLRDYISSLKMTPCIPYLGIYLSDLTYIDSAYPSTGSILENEQRSNLM
                 NNILRIISDLQQSCEYDIPMLPHVQKYLNSVQYIEELQKFVEDDNYKLSLKIEPGTST
                 PRSAASREDLVGPEVGASPQSGRKSVAAEGALLPQTPPSPRNLIPHGHRKCHSLGYNF
                 IHKMNTAEFKSATFPNAGPRHLLDDSVMEPHAPSRGQAESSTLSSGISIGSSDGSELS
                 EETSWPAFERNRLYHSLGPVTRVARNGYRSHMKASSSAESEDLAVHLYPGAVTIQGVL
                 RRKTLLKEGKKPTVASWTKYWAALCGTQLFYYAAKSLKATERKHFKSTSNKNVSVIGW
                 MVMMADDPEHPDLFLLTDSEKGNSYKFQAGNRMNAMLWFKHLSAACQSNKQQVPTNLM
                 TFE

[0384] Further analysis of the NOV12a protein yielded the following properties shown in Table 12B.

TABLE 12B
Protein Sequence Properties NOV12a
PSort     0.6500 probability located in cytoplasm; 0.1000
analysis: probability located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen);
          0.0000 probability located in endoplasmic reticulum
          (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0385] A search of the NOV12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12C.

TABLE 12C
Geneseq Results for NOV12a
		NOV 12a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB97502	Novel human protein SEQ ID NO:	1 . . . 583	557/583 (95%)	0.0
	770—Homo sapiens, 557 aa.	1 . . . 557	557/583 (95%)
	[WO200222660-A2. 21 MAR. 2002]
AAB48789	Human prostate cancer—pre-	1 . . . 583	557/583 (95%)	0.0
	disposing protein. CA7 CG04 -	1 . . . 557	557/583 (95%)
	Homo sapiens. 557 aa.
	[WO200069879-A2. 23 NOV. 2000]
AAM40386	Human polypeptide SEQ ID NO	1 . . . 355	355/355 (100%)	0.0
	3531—Homo sapiens, 361 aa.	1 . . . 355	355/355 (100%)
	[WO200153312-A1. 26 JUL. 2001]
AAB92626	Human protein sequence SEQ ID	1 . . . 279	279/279 (100%)	e−158
	NO:10923—Homo sapiens. 279 aa.	1 . . . 279	279/279 (100%)
	[EP1074617-A2. 07 FEB. 2001]
AAU21693	Novel human neoplastic disease	85 . . . 272	188/188 (100%)	e−104
	associated polypeptide #126—	1 . . . 188	188/188 (100%)
	Homo sapiens. 201 aa.
	[WO200155163-A1. 02 AUG. 2001]

[0386] In a BLAST search of public sequence datbases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12D.

TABLE 12D
Public BLASTP Results for NOV12a
		NOV12a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9ERD6	Ral-A exchange factor RalGPS2 - Mus	1 . . . 583	570/590 (96%)	0.0
	musculus (Mouse), 590 aa.	1 . . . 590	575/590 (96%)
Q9D2Y7	9130014M22Rik protein - Mus musculus	1 . . . 544	531/551 (96%)	0.0
	(Mouse), 568 aa.	1 . . . 551	536/551 (96%)
Q9D2K0	4921528G01 Rik protein - Mus musculus	60 . . . 583	513/531 (96%)	0.0
	(Mouse), 531 aa.	1 . . . 531	518/531 (96%)
O15059	KIAA0351 protein - Homo sapiens	5 . . . 583	361/587 (61%)	0.0
	(Human), 557 aa.	5 . . . 557	437/587 (73%)
Q9NW78	Hypothetical 31.9 kDa protein -	1 . . . 279	279/279 (100%)	e−157
	Homo sapiens (Human), 279 aa.	1 . . . 279	279/279 (100%)

[0387] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12E.

TABLE 12E
Domain Analysis of NOV12a
		Identities/
		Similarities
	NOV12a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
RasGEF	46 . . . 237	67/230 (29%)	3.2e−49
		147/230 (64%)
PH	458 . . . 569	20/112 (18%)	4.2e−11
		78/112 (70%)

Example 13

[0388] The NOV13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13A.

TABLE 13A
NOV 13 Sequence Analysis
                 SEQ ID NO: 35                 1513 bp
NOV13a.          ATGGGGAAGGCCCCAGGGTCCCTGTGCCCCCAGCAGGGCTCAGCCTGCCGCTCAAAG
CG128219-01
DNA Sequence     ACCCACCTCCCAGCCAGGCCGTGTCCTTGCTCACGGAGTACGCGGCCAGCCTGGGCAT
                 CTTCCTGCTCTTCCGGGAGGACCAGCCACCAGGTGAGGCCGGGCCGGGGTTCCCCTTC
                 TCGGTGAGCGCGGAACTGGATGGGGTGGTCTGCCCTGCGGGCACTGCGAATAGCAAGA
                 CGGAGGCCAAACAGCAGGCACCGCTCTCTGCCCTCTGCTACATCCCGAGTCAGCTCGA
                 GAACCCAGGTAATGGAGTCGGCCCCCTTCTACCTCCAGTCTCTCGCCCTGGCGCAGAG
                 AACATCCTGACCCATGAGCAGCGCTCCGCAGCGTTCCTGAGCGCCGGCTTTGACCTCC
                 TGTTGGACGAGCGCTCGCCATACTGCGCCTGTAAGGGGACTGTGGCTGGAGTCATCCT
                 GGAGAGGGAGATCCCGCGTGCCAGGCGCCACGTGAACCACATCTACAACCTGCTGGCT
                 CTGGGCACCGGCAGCAGCTGCTGTGCTGGCTGGCTGGAGTTCTCGGGCCAGCAGCTCC
                 ACGACTCCCATGGCCTCGTCATCGCCCCCACGGCCCTCCTCAGGTTCTTGTTCCCCCA
                 GCTCCTGCTGGCCACACAGCGGCGCCCCAACCGCAACGACCAGTCCCTGCTGCCCCCC
                 CAGCCAGGGCCCGGACCCCCATTCACCCTCAAGCCCCGCGTCTTCCTGCACCTCTACA
                 TCAGCAACACCCCCAAGGGCCCGGCCCCTCACATCAACTATCCACCCCCCTCCGAAGC
                 TGGCCTCCCGCACACCCCACCCATCCCCCTCCACGCCCATGTGCTCGGGCACCTGAAG
                 CCTGTGTGCTACGTGGCGCCCTCGCTCTGTGACACCCACGTGGGCTGCCTGTCAGCCA
                 CTCACAACCTCCCACCCTCCCCCCTCCTCCCCCTCCCTGCTCCCCTGCTGCCCCACCT
                 CGTCTCCCCACTCTACACCACCACCCTCATCCTCGCTGACTCATCCCACCACCCTCCC
                 ACTCTGAGCACGCCCATCCACACCCCGCCCTCCCTCGACACTCTCCTCGCGCCATCCC
                 TCCCACCTCCCTACGTCCGGACCGCCCTCCACCTCTTTCCACGCCCCCCCCTGCCCCC
                 TTCCGAACCCACCCCTGACACCTGCCCTCGCCTGACCCTCAACTGGAGCCTCCGGCAC
                 CCTGGCATCGAGGTTCTGCATCTCCCCACCCCCCGTCTGAAGTCCACTCCCGCCCTGG
                 GCCCTCCCTCCCGTCTCTGCAAGCCCTCCTTTCTCCCGGCCTTTCACCACGCCCCCAG
                 CCCTCTCCCCAACCCCTACCTCCTCGCCTTGAACACCTACGAGGCTGCCAACCCTGGC
                 CCCTACCACCAGCCTCCCAGGCAGCTCTCTCTCCTCCTGCACCACCACCGCCTCCGCC
                 CTTGGCCCTCCAAGCCACTCGTCCGCAAATTCACAAACTGAACCCACCCTCCGCGCGA
                 CCCAC
                 ORF Start: ATG at 1           ORF Stop: TGA at 1489
                 SEQ ID NO: 36                 496 aa    MW at 52442.1kD
NOV13a.          MGKAPRVPVPPAGLSLPLKDPPASQAVSLLTEYAASLGIFLLFREDQPPGEAGPGFPF
CG128219-01
Protein Sequence SVSAELDGVVCPAGTANSKTEAKQQAALSALCYIRSQLENPGNGVGPLLPAVSRPGAE
                 NILTHEQRCAALVSAGFDLLLDERSPYWACKGTVAGVILEREIPRARGHVKEIYKLVA
                 LGTGSSCCAGWLEFSGQQLHDCHGLVIARRALLRFLRFQLLLATQGGPKGKEQSVLAP
                 QPGPGPPGTLKPRVGLHLYISNTPKGAARDIKYAGPSEGGLPHSPPMRLQAHVLGQLK
                 PVCYVAPSLCDTHVGCLSASDKLARWAVLGLGGALLAHLVSPLYSTSLILADSCHDPP
                 TLSRAIHTRPCLDSVLGPCLPPPYVRTALHLFAGPPVAPSEPTPDTCRGLSLNWSLGD
                 PGOEVVDVATGRVKSSAALGPPSRLCKASFLRAFHQAARAVGKPYLLALKTYEAAKAG
                 PYQEARRQLSLLLDQQGLGAWPSKPLVGKFRN

[0389] Further analysis of the NOV13a protein yielded the following properties shown in Table 13B.

TABLE 13B
Protein Sequence Properties NOV13a
PSort     0.4500 probability located in cytoplasm; 0.3000 probability
analysis: located in microbody (peroxisome); 0.2469 probability located
          in lysosome (lumen); 0.1000 probability located in
          mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0390] A search of the NOV13a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13C.

TABLE 13C
Geneseq Results for NOV13a
		NOV13a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU01962	Human secreted protein	206 . . . 358	134/153 (87%)	2e−71
	immunogenic epitope encoded by	9 . . . 161	136/153 (88%)
	gene #37—Homo sapiens. 177 aa.
	[WO200123598-A1. 05 APR. 2001]
ABB89869	Human polypeptide SEQ ID NO	205 . . . 358	134/154 (87%)	2e−71
	2245—Homo sapiens. 176 aa.	8 . . . 161	136/154 (88%)
	[WO200190304-A2, 29 NOV. 2001]
AAU02011	Human secreted protein encoded by	423 . . . 494	72/72 (100%)	8e−35
	gene #37—Homo sapiens. 72 aa.	1 . . . 72	72/72 (100%)
	[WO200123598-A1, 05 APR. 2001]
ABB69810	Drosophila melanogasrer	72 . . . 490	128/460 (27%)	2e−25
	polypeptide SEQ ID NO 36222—	185 . . . 623	201/460 (42%)
	Drosophila melanogaster. 632 aa.
	[WO200171042-A2. 27 SEP. 2001]
AAW54962	Human double-stranded adenosine	30 . . . 489	136/505 (26%)	6e−23
	deaminase—Homo sapiens. 1226 aa.	731 . . . 1213	205/505 (39%)
	[US5763174-A. 09 JUN. 1998]

[0391] In a BLAST search of public sequence datbases, the NOV13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13D.

TABLE 13D
Public BLASTP Results for NOV13a
		NOV13a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
AAM22869	Hypothetical 61.8 kDa protein -	1 . . . 496	470/496 (94%)	0.0
	Homo sapiens (Human), 583 aa.	91 . . . 583	475/496 (95%)
Q95JT2	Hypothetical 59.4 kDa protein -	1 . . . 496	456/496 (91%)	0.0
	Macaca fascicularis (Crab eating	70 . . . 562	464/496 (92%)
	macaque) (Cynomolgus monkey),
	562 aa.
Q95JV3	Hypothetical 61.2 kDa protein -	1 . . . 496	456/496 (91%)	0.0
	Macaca fascicularis (Crab eating	88 . . . 580	464/496 (92%)
	macaque) (Cynomolgus monkey),
	580 aa.
Q9D5P4	4930403J07Rik protein - Mus	19 . . . 496	354/478 (74%)	0.0
	musculus (Mouse), 478 aa.	4 . . . 478	394/478 (82%)
Q62309	Testis nuclear RNA binding	27 . . . 494	163/495 (32%)	7e−52
	protein - Mus musculus (Mouse),	140 . . . 617	245/495 (48%)
	619 aa.

[0392] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13E.

TABLE 13E
Domain Analysis of NOV13a
		Identities/
		Similarities
	NOV13a	for the	Expect
Pfam Domain	Match Region	Matched Region	Value
Dsrm	26 . . . 92	19/74 (26%)	0.013
		42/74 (57%)
A_deamin	174 . . . 261	38/91 (42%)	4.4e−19
		56/91 (62%)
A_deamin	308 . . . 491	73/198 (37%)	1.6e−31
		113/198 (57%)

Example 14

[0393] 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: 37                 1754 bp
NOV14a,          TTAAAAATCATCTTTGATTATTCTTCTTTTCTAGTAAAATAATATTTAGAAAAAATAA
CG128389-01
DNA Sequence     TGTCAGAGCACAGCAGAAATTCAGATCAACAAGAACTTCTCGATGAGCAGATTAATGA
                 AGATGAAATCTTGGCCAACTTGTCTGCTGAAGAACTGAAAGAACTGCAGTCGGAAATG
                 CAAGTCATGGCCCCTGACCCCAGCCTTCCCGTGGGAATGATTCAGAAAGATCAAACTG
                 ACAACCCACCGACAGGAAACTTCAATCATAAATCTCTTCTTGATTATATGTATTGGGA
                 AAAGGCATCCACGCGCATGCTGCAAGAGGAACGAGTTCCTGTCACCTTTGTGAAATCC
                 GAGGAAAACACTCAACAACAGCATGAAGAAATAGAAAAACGTAATAAAAATATGGCCC
                 AGTATTTAAAAGAAAAGCTCAATAATGAAATAGTTGCAAATAAAAGAGAATCPAACGG
                 CAGCAGCAATATCCAAGAAACAGATGAAGAAGATGAAGAAGAAGAAGATGATGATGAT
                 GACCACGAAGCAGAACATGATGGTGAAGAGAQTGAACAAACGAACACAGAAGAGGAAG
                 GCAAAGCAAAGGAACAAATTAGAAATTGTGAGAACAACTGCCAGCACGTAACTGACAA
                 AGCATTCAAAGAACAGAGAGACAGACCAGAGGCCCAAGAACAAAGTGAGAAAAAAATA
                 TCGAAATTAGATCCTAAGAAGTTAGCTCTAGACACCAGCTTTTTGAAGGTAAGTACAA
                 GGCCTTCAGGAAACCAGACAGACCTGGATGGGAGCTTGAGGAGAGTTAGGAAAAATGA
                 TCCTGACATGAAGGAACTCAACCTGAACAACATTGAAAACATCCCCAAAGAAATGTTA
                 CTGGACTTTGTCAATGCAATGAAGAAAAACAAGCACATCAAAACATTCAGTTTAGCCA
                 ATCTCGGTGCACATGAGAATGTACCATTTCCCTTCGCTAACATCTTCCCTGAAAATAG
                 AAGCATCACCACTCTCAACATCGAGTCCAATTTCATCACAGGTAAAGGGATTCTGGCC
                 ATCATGAGGTGTCTCCAGTTTAATGAGACGCTAACTGAGCTTCGGTTTCACAATCAGA
                 GGCACATGTTGGGTCACCATGCTGAAATGGAAATAGCCAGGCTTTTGAAGGCAAACAA
                 CACTCTCCTCAAGATGGCCTACCATTTTGAGCTTCCGCGTCCCAGAATCGTGGTCACT
                 AATCTGCTCACCAGGAATCAGGATAAACAAAGGCAGAAACGACAGGAAGAGCAAAAAC
                 AGCAGCAACTCAAGGAACAGAAGAAGCTGATAGCCATGTTAGACAATGGGTTGCGGCT
                 GCCCCCTGGGATGTGGGAGCTGTTGGGAGGACCCAAGCCAGATTCCAGAATGCAGGAA
                 TTCTTCCAGCCACCGCCACCTCGGCCTCCCAACCCCCAAAATGTCCCCTTTAGTCAAC
                 GCAGTGAAATGATGAAAAAGCCATCGCAGGCCCCGAAGTACAGGACAGACCCTGACTC
                 CTTCCCGGTCGTCAAGCTGAAGAGAATCCACCGCAAATCTCGGATGCCGGAAGCCAGA
                 GAACCACCCGAGAAAACCAACCTCAAAGATGTCATCAAAACGCTCAAGCCAGTGCCGA
                 GAAACAGGCCACCCCCATTGGTGGAAATCACTCCCAGAGATCAGCTGCTAAACGACAT
                 TCGTCACAGCAGTGTCGCCTATCTTAAACCTGTAAGTACAACCACCGAGAAATCGTGA
                 CTCAGCACCCTCCA
                 ORF Start: ATG at 58          ORF Stop: TGA at 1738
                 SEQ ID NO: 38                 560 aa    MW at 65132.9kD
NOV14a.          MSEHSRNSDQEELLDEEINEDEILANLSAEELKELQSAMEVMAPDPSLPVGMIQKDQT
CC128389-01
Protein Sequence DKPPTGNFNHKSLVDYMYWEKASRRMLEEERVPVTFVKSEEKTQEEHEEIEKRNKNMA
                 QYLKEKLNNEIVANKRESKGSSNIQETDEEDEEEEDDDDDDEGEDDGEESEETNREEE
                 GKAKEQIRNCENNCQQVTDKAFKEQRDRPEAQEQSEKKISKLDPKKLALDTSFLKVST
                 RPSGNQTDLDGSLRRVRKNDPDMKELNLNNIENIPKEMLLDFVNAMKKNKHIKTFSLA
                 NVGADENVAFALANMLRENRSITTLNIESNFITGKGIVAIMRCLQFNETLTELRFHNQ
                 RHMLGHHAEMEIARLLKANNTLLKMGYHFELPGPRMVVTNLLTRNQDKQRQKRQEEQK
                 QQQLKEQKKLIAMLENGLGLPPGMWELLGGPKPDSRMQEFFQPPPPRPPNPQNVPFSQ
                 RSEMMKKPSQAPKYRTDRDSFRVVKLKRIQRKSRMPEAREPPEKTNLKDVIKTLKRVP
                 RNRPPPLVEITPRDQLLNDIRHSSVAULKPVSRRREKW

[0394] Further analysis of the NOV14a protein yielded the following properties shown in Table 14B.

TABLE 14B
Protein Sequence Properties NOV14a
Psort     0.4500 probability located in cytoplasm; 0.3000 probability
analysis: located in space; 0.1000 probability located in lysosome
          (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0395] 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 NOVl4a
		NOV 14a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAO11834	Human polypeptide SEQ ID NO	1 . . . 268	267/268 (99%)	e−152
	25726—Homo sapiens.	6 . . . 273	267/268 (99%)
	273 aa. [WO200164835-A2.
	07 SEP. 2001]
AAM25794	Human protein sequence	321 . . . 494	173/174 (99%)	3e−99
	SEQ ID NO: 1309—Homo sapiens.	1 . . . 174	174/174 (99%)
	174 aa. [WO200153455-A2.
	26 JUL. 2001]
AAB86278	Human DCMAG-1 protein—Homo	16 . . . 553	217/571 (38%)	4e−90
	sapiens. 552 aa.	14 . . . 540	308/571 (53%)
	[WO200146388-A2.
	28 JUN. 2001]
AAW90172	Human heart muscle specific	16 . . . 553	2l7/57I (38%)	4e−90
	protein—Homo sapiens.	14 . . . 540	308/571 (53%)
	552 aa. [WO9856907-A1.
	17 DEC. 1998]
AAU19573	Human diagnostic and therapeutic	8 . . . 409	175/402 (43%)	2e−85
	polypeptide (DITHP) #159—Homo	35 . . . 396	249/402 (61%)
	sapiens. 531 aa. [WO200162927-
	A2. 30 AUG. 2001]

[0396] In a BLAST search of public sequence datbases, the NOV14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14D.

TABLE 14D
Public BLASTP Results for NOV14a
		NOV14a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q96LS4	CDNA FLJ25123 fis, clone	75 . . . 443	346/369 (93%)	0.0
	CBR06154 - Homo sapiens (Human),	1 . . . 347	347/369 (93%)
	348 aa.
S18732	autoantigen, 64 K - human, 572 aa.	32 . . . 553	204/610 (33%)	2e−68
		1 . . . 565	301/610 (48%)
P29536	Leiomodin 1 (Leiomodin, muscle	32 . . . 553	204/610 (33%)	2e−68
	form) (64 kDa autoantigen D1) (64	1 . . . 565	301/610 (48%)
	kDa autoantigen 1D) (64 kDa
	autoantigen 1D3) (Thyroid-associated
	ophthalmopathy autoantigen) (Smooth
	muscle leiomodin) (SM-Lmod) -
	Homo sapiens (Human), 572 aa.
Q99PM7	Cardiac leiomodin - Mus musculus	257 . . . 553	132/331 (39%)	1e−55
	(Mouse), 333 aa (fragment).	5 . . . 326	181/331 (53%)
Q9NZR1	Tropomodulin 2 - Homo sapiens	16 . . . 407	135/393 (34%)	4e−50
	(Human), 351 aa.	13 . . . 351	206/393 (52%)

[0397] 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	Expect
Pfam Domain	Match Region	Matched Region	Value
WH2	534 . . . 553	8/21 (38%)	0.83
		17/21 (81%)

Example 15

[0398] The NOV15 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15A.

TABLE 15A
NOV 15A Sequence Analysis
                 SEQ ID NO: 39                 2768 bp
NOV15a.          GCATTGCATGTTTGTTTGCCATTGCCCCCGCCACCCTGCAAGTTGCACCTTCTAGAPA
CG128613-01
DNA Sequence     CAGCAAGCCAAGCTCCTCTCACCCAGCGTAATGATGCGGAAATGCAAATGCACCATCA
                 TGTTGTGACCCATATTGCGAAAATTAGAAAAAAGGAAGTTGTGTTTCGCTATTGCACG
                 AAGTTCAGCCCAGAGGAGAAACTCGCTCGCCTTCAGAAGACAGTACCTCCTAAATGGC
                 TCTACTTTGAACCTGCTGGGCAAGGAAGAGATTTTCAAGGAAACCATCTACCGTGTGC
                 AAGCTCCTGCCGGCCAACCCCAGACCCCAGCACCGAGCCACCCGCCTGTGCCCGCCAA
                 AAGCTCCTGCCGGCCAACCCCAGACCCCAGCACGGAGCCAGGCGCCTGTGCCCGCCAA
                 CCTCACCCCAGTCAGCTCACCTTTAAGGATGGAGTCACCCAGGGGGTCCTCAACCCCT
                 CCAGGACCCATTGCTGCCCTAGGGATGCCAGACACTGGGCCTGGCAGTTCCTCCCTAG
                 GGAAGCTTCAGGCGCTCCCTCTTGGGCCCAGAGCCCACTCTGGGCACCCTCTCACCCT
                 GCCTCCAGCAGCCCACGGCTCTCCAGACATACCCCCCACGGGAGAGCTGAGTGGTACC
                 TTAAAGATCCCCAACCCGCACAGCCGGATCGACAGTCCCTCCTCCACTGTGGCTGCAC
                 AGAACTTTCCCTCCGACGAGGCCTTCCAGGCTGGCCCAAGCCCCACTGTACTGCGCGC
                 CCACGCAGAGATCGCCCTCGACAGCCAGGTCCCGAAGGTCACCCCCCAGGAGGACGCG
                 CACAGCGACCTGGCTGAGCAACCTCACTCTGAGAACACCCCCCAGAACGCTGACAACG
                 ATCCCCCCCTGGCCCAGCACTCTGGCCCCCAGAAGCTTCTCCACATTGCCCAGCAGCT
                 CCTCCACACCCACCAGACCTATCTCAACCGCCTGCACCTGCTCCACCAGCTTTTCTGC
                 ACCACCCTGACGGATCCGCGGATCCCTCCAGAAGTCATCATCCCCATATTCTCTAACA
                 TCTCCTCCATCCACCCCTTCCACCGCCACTTCCTGCTCCCGGACCTGAAGACGCGGAT
                 CACGCAGGAGTCGCACACAAACCCACGCCTCGGCGACATCCTCCACAACCTGGCCCCA
                 TTCCTCAAGATCTACGCCGAGTATCTCAACAACTTTGACCGAGCCCTAGCGCTGCTGA
                 CCACGTGGACCCACCGCTCCCCACTGTTTAAACACCTCCTCCACACCATCCAGAACCA
                 GGACGTATGCCGGAACCTGACGCTGCACCACCACATGCTCCAGCCCGTGCAGACGGTC
                 CCCCGGTACGAGCTGCTGCTCAACCACTATCTGAAGAGCCTCCCGCACGACGCCCCAC
                 ACCGGAAGGATGCGGAGAGGTCCTTGGAGCTCATCTCCACAGCCGCCAACCACTCCAA
                 TGCTGCCATTCGGAAAGTGGAGAAAATGCACAAGCTCTTGGAGGTGTACGAGCAGCTG
                 GGTGGGGAAGAAGACATTGTCAACCCCGCCAATGAACTGATCAAGGAGGGCCAAATCC
                 AGAAACTGTCAGCCAAGAACGGCACCCCCCAGGACCGCCACCTCTTCCTGTTCAACAG
                 CATCATCCTTTACTCTCTCCCCAACCTGCGCCTCATCCCCCACAACTTCACCGTCCCC
                 GAGAAGATGGACATCTCAGGCCTCCAGGTGCAGGATATCGTCAAGCCAAACACAGCAC
                 ATACATTCATCATAACAGCAAGAAAAAGGTCCCTGCAGCTGCAGACCCGGACAGACCA
                 AGAGAAGAAAGAATGCATTCAGATCATCCAGGCCACCATCGAGAAGCACAAACAGAAC
                 ACCGAAACCTTCAAGGCTTTTGGTGGCGCCTTCAGCCAGCATGAGGACCCCAGCCTCT
                 CTCCAGACATGCCTATCACGAGCACCAGCCCTGTCGAGCCTGTGGTGACCACCGAAGG
                 CAGTTCGGGTGCAGCAGCGCTCGACCCCAGAAAACTATCCTCTAACACCAGACGTGAC
                 AAGGACAACCAGAGCTGTAAGAGCTGTGGTGAGACCTTCAACTCCATCACCAAGAGGA
                 GGCATCACTGCAAGCTGTGTGGGGCGGTCATCTGTGGGAAGTGCTCCGAGTTCAAGGC
                 CGAGAACAGCCGGCAGAGCCGTGTCTGCAGAGATTGTTTCCTCACACAGCCAGTGGCC
                 CCTGAGAGCACAGAGGTGGGTGCTCCCAGCTCCTGCTCCCCTCCTGGTGGCGCGGCAG
                 AGCCTCCAGACACCTGCTCCTGTGCCCCAGCAGCTCCAGCTGCCTCTGCTTTCGGAAA
                 GACACCCACTGCACACCCCCAGCCCAGCCTGCTCTGCGCCCCCCTGCGGCTGTCAGAG
                 AGCGGTGAGACCTGGAGCGAGGTGTGGGCCGCCATCCCCATGTCAGATCCCCAGGTGC
                 TGCACCTGCAGGGAGGCAGCCAGGACGGCCGGCTGCCCCGCACCATCCCTCTCCCCAG
                 CTGCAAACTGAGTGTGCCGGACCCTGAGGAGAGGCTGGACTCGGGGCATGTGTGGAAG
                 CTGCAGTGGGCCAAGCAGTCCTGGTACCTGAGCGCCTCCTCCGCAGAGCTGCAGCAGC
                 AGTGGCTGGAAACCCTAAGCACTGCTGCCCATGGGGACACGGCCCAGGACAGCCCGGG
                 GGCCCTCCAGCTTCAGGTCCCTATGGGCGCAGCTGCTCCGTGAGCTGAGTCTCCCACT
                 GCCCTGCACACCACCACATTGGACCTGTGCTGTCCTGGGAGG
                 ORF Start: ATG at 435         ORF Stop: TGA at 27O9
                 SEQ ID NO: 40                 758 aa    MW at 82284.0kD
NOV15a.          MESGRGSSTPRGPIAALGMPDTGPGSSSLGKLQALPVGPRAHCGDPVSLAAAGDGSPD
CG128613-01
Protein Sequence IGPTGELSGSLKIPNRDSGIDSPSSSVAGENFPCEEGLEAGPSPTVLGAHAEMALDSQ
                 VPKVTPQEEADSDVGEEPDSENTPQKADKDAGLAQHSGPQKLLHIAQELLHTEETYVK
                 RLHLLDQVFCTRLTDAGIPPEVIMGIFSNISSIHRFHGQFLLPELKTRITEEWDTNPR
                 LGDILQKLAPFLKMYGEYVKNFDRAVGLVSTWTQRSPLFKDVVHSIQKQEVCGNLTLQ
                 HHMLEPVQRVPRYELLLKDYLKRLPQDAPDRKDAERSLELISTAANHSNAAIRKVEKM
                 HKLLEVYEQLGGEEDIVNPANELIKEGQIQKLSAKNGTPQDRHLFLFNSMILYCVPKL
                 RLMGQKFSVREKMDISGLQVQDIVKPNTAHTFIITGRKRSLELQTRTEEEKKEWIQII
                 QATIEKHKQNSETFKAFGGAFSQDEDPSLSPDMPITSTSPVEPVVTTEGSSGAAGLEP
                 RKLSSKTRRDKEKQSCKSCGETFNSITKRRHHCKLCGAVICGKCSEFKAENSRQSRVC
                 RDCFLTQPVAPESTEVGAPSSCSPPGGAAEPPDTCSCAPAAPAASAFGKTPTADPQPS
                 LLCGPLRLSESGETWSEVWAAIPMSDPQVLHLQGGSQDGRLPRTIPLPSCKLSVPDPE
                 ERLDSGHVWKLQWAKQSWYLSASSAELQQQWLETLSTAAHGDTAQDSPGALQLQVPMG
                 AAAP

[0399] Further analysis of the NOV15 a protein yielded the following properties shown in Table 15B.

TABLE 15B
Protein Sequence Properties NOV15a
PSort     0.3000 probability located in nucleus; 0.1000 probability
analysis: located in mitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen); 0.0000 probability located in
          endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0400] A search of the NOV15a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15C.

TABLE 15C
Geneseq Results for NOV15a
		NOV15a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU27818	Human Full-length polypeptide	1 . . . 758	725/758 (95%)	0.0
	sequence #143—Homo	1 . . . 725	725/758 (95%)
	sapiens. 725 aa.
	[WO200164834-A2.
	07 SEP. 2001]
AAU17096	Novel signal transduction	1 . . . 565	559/565 (98%)	0.0
	pathway protein. Seq ID 661—	65 . . . 629	559/565 (98%)
	Homo sapiens. 687 aa.
	[WO200154733-A1. 02 AUG. 2001]
AAU17364	Novel signal transduction	178 . . . 525	287/351 (81%)	e−158
	pathway protein. Seq ID 929—	11 . . . 351	300/351 (84%)
	Homo sapiens. 363 aa.
	[WO200154733-A1. 02 AUG. 2001]
AAU21631	Novel human neoplastic disease	1 . . . 247	232/248 (93%)	e−132
	associated polypeptide #64—Homo	65 . . . 312	233/248 (93%)
	sapiens. 332 aa.
	[WO200155163-A1. 02 AUG. 2001]
AAU17448	Novel signal transduction pathway	1 . . . 247	232/248 (93%)	e−132
	protein. Seq ID 1013—Homo	65 . . . 312	233/248 (93%)
	sapiens. 332 aa.
	[WO200154733-A1. 02 AUG. 2001]

[0401] In a BLAST search of public sequence datbases, the NOV15a protein was found to have homology to the proteins shown in the BLASTP data in Table 15D.

TABLE 15D
Public BLASTP Results for NOV15a
		NOV15a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9NXY1	FLJ00004 protein - Homo sapiens	1 . . . 628	626/628 (99%)	0.0
	(Human), 698 aa (fragment).	65 . . . 692	627/628 (99%)
O88842	Faciogenital dysplasia protein 3 -	1 . . . 758	551/759 (72%)	0.0
	Mus musculus (Mouse), 733 aa.	1 . . . 733	605/759 (79%)
O93504	Faciogenital dysplasia protein -	58 . . . 595	338/554 (61%)	0.0
	Brachydanio rerio (Zebrafish) (Zebra	52 . . . 587	402/554 (72%)
	danio), 621 aa.
P98174	Putative Rho/Rac guanine nucleotide	11 . . . 744	355/758 (46%)	e−180
	exchange factor (Rho/Rac GEF)	232 . . . 929	460/758 (59%)
	(Faciogenital dysplasia protein) -
	Homo sapiens (Human), 961 aa.
Q921L2	Similar to faciogenital dysplasia	10 . . . 744	356/757 (47%)	e−179
	homolog - Mus musculus (Mouse),	238 . . . 928	458/757 (60%)
	960 aa.

[0402] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15E.

TABLE 15E
Domain Analysis of NOV15a
		Identities/
		Similarities
	NOV15a	for the	Expect
Pfam Domain	Match Region	Matched Region	Value
RhoGEF	161 . . . 340	75/207 (36%)	8.1e−64
		155/207 (75%)
PH	371 . . . 469	31/99 (31%)	2.8e−17
		79/99 (80%)
DAG_PE-bind	528 . . . 574	13/51 (25%)	0.99
		25/51 (49%)
FYVE	532 . . . 584	23/62 (37%)	2.8e−12
		46/62 (74%)
PH	638 . . . 736	16/99 (16%)	9e−06
		71/99 (72%)

Example 16

[0403] The NOV 16 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16A.

TABLE 16A
NOV16 Sequence Analysis
                 SEQ ID NO: 41                 1944 bp
NOV16a.          CAGCCCGCGACAACTCCCGCCACCTACGGGGCCTCAGAGAAGCCGGACTTCGCAAGCA
CC128685-01
DNA Sequence     CCATGCAGTGGATAACGGGCGGATCGGGAATGCTCATCACTGGAGATTCCATCCTTAG
                 TGCTGAGGCAGTATGCGATCACGTCACCATGGCCAACCGGGAGTTGGCATTTAAAGCT
                 GGCGACGTCATCAAAGTCTTGGATGCTTCCAACAAGGATTGGTGGTGGGGCCAGATCG
                 ACGATGAGGAGGGATGGTTTCCTGCCAGCTTTGTGAGGCTCTGGGTGAACCAGGAGGA
                 TGAGGTGGACGAGGCGCCCAGCGATGTGCAGAACGCACACCTGCACCCCAATTCAGAC
                 TGCCTCTGTCTCGGGCGGCCACTACAGAACCGGGACCAGATGCGGGCCAATGTCATCA
                 ATGACATAATGACCACTGAGCGTCACTACATCAAGCACCTCAAGGATATTTGTGAGGG
                 CTATCTGAAGCACTGCCGGAAGAGAAGGCACATGTTCACTGACGAGCAACTGAAGGTA
                 ATCTTTGGGAACATTGAAGATATCTACAGATTTCAGATGGGCTTTGTGAGAGACCTGG
                 AGAAACAGTATAACAATGATCACCCCCACCTCAGCCAGATAGCACCCTGCTTCCTAGA
                 GCACCAAGATGGATTCTGGATATACTCTGAGTATTCTAACAACCACCTGGATGCTTGC
                 ATGGAGCTCTCCAAACTGATGAAGGACAGCCGCTACCAGCACTTCTTTGAGGCCTGTC
                 GCCTCTTGCAGCAGATCATTGACATTGCTATCGATCGTTTCCTTTTGACTCCAGTGCA
                 GAAGATCTGCAAGTATCCCTTACAGTTGGCTGACCTCCTAAACTATACTGCCCAAGAC
                 CACAGTGACTACAGGTATGTGGCAGCTGCTTTGGCTGTCATOAGAAATGTGACTCAGC
                 ACATCAACCAACGCAACCCACGTTTAGAGAATATTGACAAGATTGCTCACTCCCACCC
                 TTCTCTCCTAGACTCGCACCCCGAGGACATCCTAGACACGAGCTCCCAGCTCATCTAC
                 ACTCGCGAGATCCCCTCCATCTACCAGCCCTACCGCCGCAACCAGCAGCGGCTCTTCT
                 TCCTCTTTCACCACCAGATCCTCCTCTCCAACAAGGACCTAATCCCGACAGACATCCT
                 GTACTACAAAGGCCGCATTGACATGGATAAATATGAGGTAGTTGACATTGAGGATGGC
                 AGAGATGATGACTTCAATGTCAGCATGAAGAATGCCTTTAAGCTTCACAACAAGGAGA
                 CTGAGCAGATACATCTCTTCTTTCCCAACAAGCTCCAGCAAAAAATACCCTGCCTCAC
                 GGCTTTCAGAGAAGAGAGGAAAATGGTACAGGAAGATGAAAAAATTGGCTTTGAAATT
                 TCTGAAAACCAGAAGAGGCAGGCTGCAATGACTGTGAGAAAAGTCCCTAAGCAAAAAG
                 GTGTCAACTCTGCCCGCTCAGTTCCTCCTTCCTACCCACCACCGCAGGACCCGTTAAA
                 CCACCGCCACTACCTGGTCCCCGACGGCATCGCTCACTCGCACGTCTTTCACTTCACC
                 GAACCCAAGCGCAGCCAGTCACCATTCTGGCAAAACTTCAGCAGGTTAACCCCCTTCA
                 AAAAATGATACCTACAGGGAGGCAGATAATTTTAAAATAAAGTAAATAAAATTATAAT
                 AGATGGACCTTTTTTCGGAGAAGCACTGTTGAAATTTATACACACACACACACACAGA
                 CACACACACACAGAGAGATAAGGAACAAAAGTGTTTTCTGTTGTTTTGGGGAAGTGAA
                 GACCCTTGAGTACACATACACACACACACACACACACACACACACACACACACACACA
                 CACACACACACAGAGAGATAAGGAACAAAAGTGTTTTCTGTTGTTTTGGGGAAGTGAA
                 ATATGTGGTTGGTAGGAAGAGGTACCAATGACTTCCAAACATGTGATTCCGTCTTAAA
                 AGTTTTCCATTTTTACCCTGTCCCCCTTCC
                 ORF Start: ATC at 61          ORF Stop: TGA at 1630
                 SEQ ID NO: 42                 593 aa    MW at 61740.5kD
NOV16a.          MQWIRGGSGMLITGDSIVSAEAVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQID
CC128685-01
Protein Sequence DEEGWFPASPVRLWVNQEDEVEEGPSDVQNCHLDPNSDCLCLCRPLQNRDQMRANVIN
                 EIMSTERHYIKHLKDICECYLKQCRKRRDMFSDEQLKVIFGNTEJDTYRVQMGFVRDLE
                 KQYNNDDPHLSEIGPCFLEHQDGFWIYSEYCNNHLDACMELSKLMKDSRYQHFFEACR
                 LLQQMIDIAIDGFLLTPVQKICKYPLQLAELLKYTAQDHSDYRTVAAALAVMRNVTQQ
                 INERKRRLENIDKIAQWQASVLDWEGEDILDRSSELIYTGEMAWIYQPYGRNQQRVFF
                 LFDHQMVLCKKDLIRRDILYYKGRIDMDKYEVVDIEDGRDDDFNVSMKNAFKLHNKET
                 EEIHLFFAKKLEEKIRWLRAFREERKMVQEDEKIGFEISENQKRQAAMTVRKVPKQKG
                 VNSARSVPPSYPPPQDPLNHGQYLVPDGIAQSQVFEFTEPKRSQSPFWQNFSRLTPFK
                 K

[0404] 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 nucleus; 0.5159 probability
analysis: located in microbody (peroxisome); 0.1000 probability
          located in mitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0405] 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	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM39338	Human polypeptide SEQ ID NO	1 . . . 523	523/523 (100%)	0.0
	2483 - Homo sapiens. 523 aa.	1 . . . 523	523/523 (100%)
	[WO200153312-A1. 26 JUL. 2001]
AAM41124	Human polypeptide SEQ ID NO	10 . . . 523	512/514 (99%)	0.0
	6055 - Homo sapiens, 647 aa.	134 . . . 647	513/514 (99%)
	[WO200153312-A1, 26 JUL. 2001]
AAB97025	Human colon carcinoma	11 . . . 523	304/518 (58%)	e−179
	suppressor gene-related protein -	119 . . . 619	383/518 (73%)
	Homo sapiens. 619 aa.
	[JP2001057888-A. 06 MAR. 2001]
AAU17071	Novel signal transduction pathway	258 . . . 523	263/266 (98%)	e−153
	protein. Seq ID 636 - Homo	3 . . . 268	265/266 (98%)
	sapiens. 268 aa. [WO200154733-
	A1. 02 AUG. 200l]
AAM84301	Human immune/haematopoietic	258 . . . 523	263/266( 98%)	e−153
	antigen SEQ ID NO:11894 - Homo	3 . . . 268	265/266 (98%)
	sapiens. 268 aa. [WO200157182-
	A2. 09 AUG. 2001]

[0406] In a BLAST search of public sequence datbases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16D.

TABLE 16D
Public BLASTP Results for NOV16a
		NOV16a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O43307	KIAA0424 protein - Homo sapiens	10 . . . 523	513/514 (99%)	0.0
	(Human), 516 aa.	3 . . . 516	514/514 (99%)
Q9QX73	Collybistin I - Rattus norvegicus	1 . . . 464	456/464 (98%)	0.0
	(Rat), 493 aa.	1 . . . 464	460/464 (98%)
Q9ER22	Collybistin II - Rattus norvegicus	63 . . . 463	388/401 (96%)	0.0
	(Rat), 411 aa.	3 . . . 403	391/401 (96%)
Q96N96	CDNA FLJ31208 fis, clone	11 . . . 523	318/520 (61%)	0.0
	KIDNE2003373, moderately similar	143 . . . 652	395/520 (75%)
	to Homo sapiens Asef APC-
	stimulated guanine nucleotide
	exchange factor - Homo sapiens
	(Human), 652 aa.
Q9HDC6	APC-stimulated guanine nucleotide	11 . . . 523	304/518 (58%)	e−179
	exchange factor - Homo sapiens	119 . . . 619	383/518 (73%)
	(Human), 619 aa.

[0407] 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	Expect
Pfam Domain	Match Region	Matched Region	Value
SH3	18 . . . 72	20/58 (34%)	4.1e−07
		38/58 (66%)
RhoGEF	114 . . . 293	58/207 (28%)	9.5e−35
		125/207 (60%)
PH	326 . . . 432	21/107 (20%)	9.1e−11
		81/107 (76%)
CSD	434 . . . 459	12/28 (43%)	0.33
		20/28 (71%)

Example 17

[0408] The NOV17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A.

TABLE 17A
NOV 17 Sequence Analysis
                 SEQ ID NO. 43           1359bp
NOV 17a.         GCGCCCGAACCCGCGGCGGCGGTGGGGACGATGTGGTTCTTTGCCCGGGACCCGGTC
CG128937-01
DNA Sequence     GGGACTTTCCGTTCGAGCTCATCCCGGAGCCCCCAGAGGGCGGCCTGCCCGGGCCCTG
                 GGCCCTGCACCGCGGCCGCAAGAAGGCCACAGGCAGCCCCGTGTCCATCTTCGTCTAT
                 GATGTGAAGCCTGGCGCGGAAGAGCAGACCCAGGTGGCCAAAGCTGCCTTCAAGCGCT
                 TCAAAACTCTACGGCACCCCAACATCCTGGCTTACATCGATGGACTGGAGACAGAAAA
                 ATGCCTCCACGTCGTGACAGAGGCTGTGACCCCGTTGGGAATATACCTCAAGGCGAGA
                 GTGGAGGCTGGTGGCCTGAAGGAGCTGGAGATCTCCTGGGGGCTACACCAGATCGTGA
                 AAGCCCTCAGCTTCCTGGTCAACGACTGCAGCCTCATCCACAACAATGTCTGCATGGC
                 CGCCGTGTTCGTGGACCGAGCTGGCGAGTGGAAGCTTGGGGGCCTGGACTACATGTAT
                 TCGGCCCAGGGCAACGGTGGGGGACCTCCCCGCAAGGGGATCCCCGAGCTTGAGCAGT
                 ATGACCCCCCGGAGTTGGCTGACAGCAGTGGCAGAGTGGTCAGAGAGAAGTGGTCAGC
                 AGACATGTGGCGCTTGGGCTGCCTCATTTGGGAAGTCTTCAATGGGCCCCTACCTCGG
                 GCAGCAGCCCTACGCAACCCTGGGAAGATCCCCAAAACGCTGGTGCCCCATTACTGTG
                 AGCTGGTGGGAGCAAACCCCAAGGTGCGTCCCAACCCAGCCCGCTTCCTGCAGAACTG
                 CCGGGCACCTGGTGGCTTCATGAGCAACCGCTTTGTAGAAACCAACCTCTTCCTGGAG
                 GAGATTCAGATCAAAGAGCCAGCCGAGAAGCAAAAATTCTTCCAGGAGCTGAGCAAGA
                 GCCTGGACGCATTCCCTGAGGATTTCTGTCGGCACAAGGTGCTGCCCCAGCTGCTGAC
                 CGCCTTCGAGTTCGGCAATGCTGGGGCCGTTGTCCTCACGCCCCTCTTCAAGGTGGGC
                 AAGTTCCTGAGCGCTGAGGAGTATCAGCAGAAGATCATCCCTGTGGTGGTCAAGATGT
                 TCTCATCCACTGACCGGGCCATGCGCATCCGCCTCCTGCAGCAGATGGAGCAGTTCAT
                 CCAGTACCTTGACGAGCCAACAGTCAACACCCAGATCTTCCCCCACGTCGTGCTAGTC
                 AGGTCAGCAACTCCGACCACAAATCCTCCAAATCCCCAGAGTCCGACTGGAGCAGCTG
                 GGAAGCTGAGGGCTCCTGGGAACAGGGCTGGCAGGAGCAAGCTCCCAGGAGCCACCTC
                 CTGACGGTACACGGCTGGCCAGCGA
                 ORF Start: ATG at 31    ORF Stop: TGA at 1336
                 SEQ ID NO: 44           435 aa    MW at 48383.5kD
NOV 17a.         MWFFARDPVRDFPFELIPEPPEGGLPGPWALHRGRKKATGSPVSIFVYDVKPGAEEQT
CG128937-01
Protein Sequence QVAKAAGKRFKTLRHPNILAYIDGLETEKCLHVVTEAVTPLGIYLKARVEAGGLKELE
                 ISWGLHQIVKALSFLVNDCSLIHNNVCMAAVFVDRAGEWKLGGLDYMYSAQGNGGGPP
                 RKGIPELEQYDPPELADSSGRVVREKWSADMWRLGCLIWEVFNGPLPRAAALRNPGKI
                 PKTLVPHYCELVGANPKVRPNPARFLQNCRAPGGFMSNRFVETNLFLEEIQIKEPAEK
                 QKFFQELSKSLDAFPEDFCRHKVLPQLLTAFEFGNAGAVVLTPLFKVGKFLSAEEYQQ
                 KIIPVVVKMFSSTDRAMRIRLLQQMIQFIQYLDEPTVNTQIFPHVVLVRSATPTTNPP
                 NPQSPTGAAGKLRAPGNRAGRSKLPGATS

[0409] Further analysis of the NOV17a protein yielded the following properties shown in Table 17B.

TABLE 17B
Protein Sequence Properties NOV17a
PSort     0.5151 probability located in microbody (peroxisome);
analysis: 0.4500 probability located in cytoplasm; 0.2278
          probability located in lysosome (lumen); 0.1000
          probability located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0410] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17C.

TABLE 17C
Geneseq Results for NOV17a
		NOV17a	Identities/
		Residues	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB65679	Novel protein kinase, SEQ ID NO:	1 . . . 394	394/394 (100%)	0.0
	207- Homo sapiens, 808 aa.	1 . . . 394	394/394 (100%)
	[WO200073469-A2, 07 DEC. 2000]
AAE11780	Human kinase (PKIN)-14 protein -	1 . . . 394	394/394 (100%)	0.0
	Homo sapiens, 791 aa.	1 . . . 394	394/394 (100%)
	[WO200181555-A2. 01 NOV. 2001]
AAB43354	Human ORFX ORF3118	1 . . . 394	394/394 (100%)	0.0
	polypeptide sequence SEQ ID	13 . . . 406	394/394 (100%)
	NO:6236 - Homo sapiens. 820 aa.
	[WO200058473-A2, 05 OCT. 2000]
AAB74457	Human Traf4 binding protein	1 . . . 394	392/394 (99%)	0.0
	MKinase - Homo sapiens. 832 aa	24 . . . 417	393/394 (99%)
	[WO200121799-A1. 29 MAR. 2001]
AAM40778	Human polypeptide SEQ ID NO	84 . . . 394	306/338 (90%)	e−176
	5709 - Homo sapiens. 675 aa.	8 . . . 345	308/338 (90%)
	[WO200153312-A1. 26 JUL. 2001]

[0411] In a BLAST search of public sequence datbases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17D.

TABLE 17D
Public BLASTP Results for NOV17a
		NOV17a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96KG8	Kinase-like protein splice variant	1 . . . 394	394/394 (100%)	0.0
	1 - Homo sapiens (Human), 791	1 . . . 394	394/394 (100%)
	aa.
Q96KG9	Kinase-like protein - Homo	1 . . . 394	394/394 (100%)	0.0
	sapiens (Human), 808 aa.	1 . . . 394	394/394 (100%)
Q96KH1	Kinase-like protein splice variant	1 . . . 394	394/394 (100%)	0.0
	2 - Homo sapiens (Human), 707	1 . . . 394	394/394 (100%)
	aa.
Q9HAW5	Telomerase regulation-associated	1 . . . 394	380/394 (96%)	0.0
	protein - Homo sapiens (Human),	1 . . . 394	382/394 (96%)
	786 aa.
Q9EQC5	105-kDa kinase-like protein -	1 . . . 393	372/393 (94%)	0.0
	Mus musculus (Mouse), 806 aa.	1 . . . 393	378/393 (95%)

[0412] PFam analysis predicts that the NOV17a protein contains the domains shown in the Table 17E.

TABLE 17E
Domain Analysis of NOV17a
Pfam Domain	NOV17a	Identities/	Expect
	Match Region	Similarities	Value
		for the
		Matched Region

Example 18

[0413] 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:45            1117 bp
NOV18a.          CCTGCCATGGCGGCTTCTGCGGCGGAGACGCGCGTGTTTCTGGAGGTGCGGGGACAGC
CG132095-01
DNA Sequence     TGCAGAGCGCGCTTCTGATCCTGGGGGAACCGAAAGAAGGAGGTATGCCCATGAATAT
                 TTCCATAATGCCATCTTCACTCCAGATGAAAACCCCTGAAGGCTGCACAGAAATCCAG
                 CTTCCAGCAGAGGTCAGGCTTGTACCTTCCTCTTGCCGTGGGCTACAGTTTGTTGTTG
                 GAGATGGACTGCACCTGCGACTGCAGACGCAAGCAAAAATTTCAATGTTTAATCAAAG
                 CTCGCAAACCCAAGAATGTTGCACGTTTTATTGCCAATCCTGCGGTGAAGTCATAATA
                 AAAGACAGGAAGCTCCTCAGGGTGCTCCCACTGCCGAGTGAGAACTGGGGAGCTCTAG
                 TTGGAGAATGGTGTTGTCATCCTGACCCCTTTGCTAATAAATCACTTCATCCGCAAGA
                 GAATGACTGTTTTATTGGAGACTCTTTCTTCTTGGTGAATTTAAGAACCAGTTTGTGG
                 CAGCAGGAACCAAAGGCAAATACCAAAGTAATTTGTAAGCGTTGCAAGGTAATGTTGG
                 GAGAGACCGTGTCATCAGAAACCACCAAGTTTTATATGACAGAGATAATTATTCAGTC
                 ATCTGAGAGGAGTTTTCCTATCATACCAAGGTCTTGGTTTGTCCAGAGCGTGATCGCC
                 CAGTGTCTGGTGCAGCTCTCCTCTGCTAGAAGCACTTTTAGATTCACGATTCAAGGTC
                 AGGATGACAAAGTGTATATCTTGCTATGGCTTTTAAATTCAGACAGTTTGGTGATTGA
                 ATCTTTGAGAAATTCCAAATATATCAAAAAATTCCCCTTGTTGGAAAACACATTCAAA
                 GCCGATTCTAGTTCTGCCTGGAGTGCTGTCAAGGTCCTCTACCAGCCATGCATCAAAA
                 GCAGGAATGAAAAGCTTGTCAGCTTGTGGGAAAGTGACATCAGCGTCCACCCGCTAAC
                 CCTGCCCTCTGCAACCTGCTTGGAGCTGCTGTTGATATTGTCAAAGAGTAATGCCAAT
                 CTGCCTTCATCCCTTCGCCGTGTGAATTCCTTTCAGGTGAGCAATGGCTTCTTTTCTA
                 GGCCGTGATTTCTCA
                 ORF Start: ATG at7      ORF Stop: TGA at 1108
                 SEQ ID NO: 46           367 aa    MW at 41216.3kD
NOV18a           MAASAAETRVFLEVRGQLQSALLILGEPKEGGMPMNISIMPSSLQMKTPEGCTEIQLP
CG132095-01
Protein Sequence AEVRLVPSSCRGLQGVVGDGLHLRLQTQAKISMFNQSSQTQECCTFYCQSCGEVIIKD
                 RKLLRVLPLPSENWGALVGEWCCHPDPFANKSLHPQENDCFIGDSFFLVNLRTSLWQQ
                 EPKANTKVICKRCKVMLGETVSSETTKFYMTEIIIQSSERSFPIIPRSWFVQSVIAQC
                 LVQLSSARSTFRFTIQGQDDKVYILLWLLNSDSLVIESLRNSKYIKKFPLLENTFKAD
                 SSSAWSAVKVLYQPCIKSRNEKLVSLWESDISVHPLTLPSATCLELLLILSKSNANLP
                 SSLRRVNSFQVSNGFFSRP
                 SEQ ID NO: 47           144 BP
NOV18b,          CCTGCCATGGCGGCTTCTGCGGCGGAGACGCGCGTGTTTCTGGAGGTGCGGGGACAGC
CG132095-02
DNA Sequence     TGCAGAGCGCGCTTCTGATCCTGGGAGAACCGAAAGAAGGAGGTATGCCCATGAATAT
                 TTCCATAATGCCATCTTCACTCCAGATGAAAACCCCTGAAGGCTGCACAGAAATCCAG
                 CTTCCAGCAGAGGTCAGGCTTGTACCTTCCTCTTGCCGTGGGCTACAGTTTGTTGTTG
                 GAGATGGACTGCACCTGCGACTGCAGACGCAAGCAAAATTAGGCACAAAACTGATTTC
                 AATGTTTAATCAAAGCTCGCAAACCCAAGAATGTTGCACGTTTTATTGCCAATCCTGC
                 GGTGAAGTCATAATAAAAGACAGGAAGCTCCTCAGGGTGCTCCCACTGCCGAGTGAGA
                 ACTGGGGAGCTCTAGTTGGAGAATGGTGTTGTCATCCTGACCCCTTTGCTAATAAATC
                 ACTTCATCCGCAAGAGAATGACTGTTTTATTGGAGACTCTTTCTTCTTGGTGAATTTA
                 AGAACCAGTTTGTGGCAGCAAAGACCTGAACTATCCCCAGTGGAGATGTGCTGTGTTT
                 CTTCTGACAACCATTGTAAATTGGAACCAAAGGCAAATACCAAAGTAATTTGTAAGCG
                 TTGCAAGGTAATGTTGGGAGAGACCGTGTCATCAGAAACCACCAAGTTTTATATGACA
                 GAGATAATTATTCAGTCATCTGAGAGGAGTTTTCCTATCATACCAAGGTCTTGGTTTG
                 TCCAGAGCGTGATCGCCCAGTGTCTGGTGCAGCTCTCCTCTGCTAGAAGCACTTTTAG
                 ATTCACGATTCAAGGTCAGGATGACAAAGTGTATATCTTGCTATGGCTTTTAAATTCA
                 GACAGTTTGGTGATTGAATCTTTGAGAAATTCCAAATATATCAAAAAATTCCCCTTGT
                 TGGAAAACACATTCAAAGCCGATTCTAGTTCTGCCTGGAGTGCTGTCAAGGTCCTCTA
                 CCAGCCATGCATCAAAAGCAGGAATGAAAAACTTGTCAGCTTGTGGGAAAGTGACATC
                 AGCGTCCACCCGCTAACCCTGCCCTCTGCAACCTGCTTGGAGCTGCTGTTGATATTGT
                 CAAAGAGTAATGCCAATCTGCCTTCATCCCTTCGCCGTGTGAATTCCTTTCAGGTGAG
                 CAATGGCTTCTTTTCTAGGCCGTGATTTCTC
                 ORF Start: ATG at 7     ORF Stop: TGA at 1183
                 SEQ ID NO: 48           392 aa    MW at 43958.5kD
NOV18b.          MAASAAETRVFLEVRGQLQSALLILGEPKEGGMPMNISIMPSSLQMKTPEGCTEIQLP
CG132095-02
Protein Sequence AEVRLVPSSCRGLQFVVGDGLHLRLQTQAKLGTKLISMFNQSSQTQECCTFYCQSCGE
                 VIIKDRKLLRVLPLPSENWGALVGEWCCHPDPFANKSLHPQENDCFIGDSFFLVNLRT
                 SLWQQRPELSPVEMCCVSSDNJCKLEPKANTKVICKRCKVMLGETVSSETTKFYMTEI
                 IIQSSERSFPIIPRSWFVQSVIAQCLVQLSSARSTFRFTIQGQDDKVYILLWLLNSDS
                 LVIESLRNSKYIKKFPLLENTFKADSSSAWSAVKVLYQPCIKSRNEKLVSLWESDISV
                 HPLTLPSATCLELLLILSKSNANLPSSLRRVNSFQVSNGFFSRP

[0414] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 18B.

TABLE 18B
Comparison of NOV18a against NOV18b.
			Identities/
		NOV18a Residues/	Similarities for
	Protein Sequence	Match Residues	the Matched Region
	NOV18b	1 . . . 367	367/392 (93%)
		1 . . . 392	367/392 (93%)

[0415] Further analysis of the NOV18a protein yielded the following properties shown in Table 18C.

TABLE 18C
Protein Sequence Properties NOV18a
PSort     0.5044 probability located in mitochondrial matrix
analysis: space; 0.4500 probability located in cytoplasm; 0.2257
          probability located in mitochondrial inner membrane;
          0.2257 probability located in mitochondrial intermembrane
          space
SignalP   No Known Signal Sequence Predicted
analysis:

[0416] A search of the NOV18a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 18D.

TABLE 18D
Geneseq Results For NOV18a
		NOV 18a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length[Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
ABB6344	Drosophila melanogaster	95 . . . 195	31/107 (28%)	1.7
	polypeptide SEQ ID NO 16365 -	123 . . . 224	44/107 (40%)
	Drosophila melanogaster. 482 aa.
	[WO200171042-A2. 27 SEP. 2001]
AAB11934	Human MEKK5 - Homo sapiens.	208 . . . 317	26/116 (22%)	4.9
	1374 aa. [US6080546-A.	494 . . . 589	52/116 (44%)
	27 JUN. 2000]
AAW27283	Apoptosis inducing protein ASK1 -	208 . . . 317	26/116 (22%)	4.9
	Homo sapiens. 1375 aa	494 . . . 589	52/116 (44%)
	[WO9740143-A1. 30 OCT. 1997]

[0417] In a BLAST search of public sequence datbases, the NOV18a protein was found to have homology to the proteins shown in the BLASTP data in Table 18E.

TABLE 18E
Public BLASTP Results for NOV18a
		NOV18a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9D0H0	2610018103Rik protein - Mus	1 . . . 360	282/365 (77%)	e−162
	musculus (Mouse), 368 aa.	1 . . . 364	323/365 (88%)
Q9NT42	Hypothetical 20.4 kDa protein -	45 . . . 197	153/178 (85%)	2e−83
	Homo sapiens (Human), 182 aa	1 . . . 178	153/178 (85%)
	(fragment).
P47172	Hypothetical 39.9 kDa protein in	106 . . . 360	61/263 (23%)	4e−08
	HOM6-PMT4 intergenic region -	111 . . . 342	108/263 (40%)
	Saccharomyces cerevisiae (Baker's
	yeast), 347 aa.
Q9BL30	Hypothetical 80.0 kDa protein -	106 . . . 359	59/284 (20%)	0.005
	Caenorhabditis elegans, 716 aa.	437 . . . 707	113/284 (39%)
O74751	Hypothetical 37.4 kDa protein -	125 . . . 359	54/243 (22%)	0.031
	Schizosaccharomyces pombe	105 . . . 321	97/243 (39%)
	(Fission yeast), 332 aa.

[0418] PFam analysis predicts that the NOV18a protein contains the domains shown in the Table 18F.

TABLE 18F
Domain Analysis of NOV18a
Pfam Domain	NOV18a	Identities/	Expect
	Match Region	Similarities for	Value
		the Matched Region

Example 19

[0419] 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: 49           8848 bp
NOV19a.          TATAACGGTACCGGCGGCGGCAGCGCCGCTGCTCTTCCCTTCTCCTCAGGAGGGGGGC
CG132414-01
DNA Sequence     CAATGGCTAGCGAGAAGCCGGGCCCGGGCCCGGGGCTCGAGCCTCAGCCCGTGGGGCT
                 CATTGCCGTCGGGGCCGCTGGCGGAGGCGGCGGGGGCAGCGGTGGTGGCGGCACCGGG
                 GGCAGCGGGATGGGGGAGCTAAGGGGGGCGTCCGGCTCCGGCTCGGTGATGCTCCCCG
                 CGGGGATGATTAACCCTTCGGTGCCGATCCGCAACATCCGGATGAAATTCGCAGTGTT
                 GATTGGACTCATACAGGTCGGAGAGGTCAGCAACAGGGACATCGTGGAGACGGTGCTC
                 AACCTGCTGGTTGGTGGAGAATTTGACTTGGAGATGAACTTTATTATCCAGGATGCTG
                 AGAGTATAACATGTATGACAGAGCTTTTGGAGCACTGTGATGTAACATGTCAAGCAGA
                 AATATGGAGCATGTTTACAGCCATTCTACGAAAAAGTGTTCGGAATTTACAGACTAGC
                 ACAGAAGTTGGGCTAATTGAACAAGTATTGCTGAAAATGAGTGCTGTAGATGACATGA
                 TAGCAGATCTTCTAGTTGATATGTTGGGGGTTCTTGCCAGCTACAGCATCACTGTCAA
                 GGAGTTGAAGCTTTTGTTCAGCATGCTTCGAGGAGAAAGTGGAATCTGGCCAAGACAT
                 GCAGTAAAATTATTATCAGTTCTTAATCAGATGCCACAGAGACACGGTCCTGATACTT
                 TTTTCAATTTCCCTGGTTGTAGCGCTGCGGCAATTGCCTTGCCTCCTATTGCAAAGTG
                 GCCTTATCAGAATGGCTTCACCTTAAACACTTGGTTTCGTATGGATCCATTAAATAAT
                 ATTAATGTTGATAAGGATAAACCTTATCTTTATTGTTTTCGTACTAGCAAAGGAGTTG
                 GTTACTCTGCTCATTTTGTTGGCAACTGTTTAATAGTCACATCATTGAAGTCCAAAGG
                 AAAAGGTTTTCAGCATTGTGTGAAATATGATTTTCAACCACGCAAGTGGTACATGATC
                 AGCATTGTCCACATTTACAATCGATGGAGGAACAGTGAAATTCGGTGTTATGTTAATG
                 GACAACTGGTATCTTATGGTGATATGGCTTGGCATGTTAACACAAATGATAGCTATGA
                 CAAGTGCTTTCTTGGATCATCAGAAACTGCTGATGCAAATAGGGTATTCTGTGGTCAA
                 CTTGGTGCCGTGTATGTGTTCAGTGAAGCACTCAACCCAGCACAGATATTTGCAATTC
                 ATCAGTTAGGACCTGGATATAAGAGTACCTTCAAGTTTAAATCTGAGAGTGATATTCA
                 TTTGGCAGAACATCATAAACAGGTGTTATATGATGGGAAACTTGCAAGTAGCATTGCC
                 TTTACATATAATGCTAAGGCCACTGATGCTCAGCTCTGCCTGGAATCATCACCAAAAG
                 AGAATGCATCAATTTTTGTGCATTCCCCACATGCTCTAATGCTTCAGGATGTGAAAGC
                 GATAGTAACACATTCAATTCATAGTGCAATTCATTCAATTGGAGGGATTCAAGTGCTT
                 TTTCCACTTTTTGCCCAATTGGATAATAGGCAGCTCAATGACAGTCAAGTGGAAACAA
                 CTGTTGCTACTCTGTTGGCATTCCTGGTTGAACTACTTAAAAGTTCAGTAGCCATGCA
                 AGAACAGATGCTGGGTGGAAAAGGCTTTTTAGTCATTGGCTACTTACTTGAAAAGTCA
                 TCAAGAGTTCATATAACTAGAGCTGTCCTGGAGCAATTTTTATCTTTTGCAAAATACC
                 TTGATGGTTTATCTCATGGAGCACCTTTGCTGAAGCAGCTTTGTGATCACATTTTATT
                 TAACCCAGCCATCTGGATACATACACCTGCAAAGGTTCAGCTTTCCCTATACACATAT
                 TTGTCTGCTGAATTTATTGGAACTGCTACCATCTACACCACCATACGCAGAGTAGGAA
                 CAGTATTACAGCTAATGCACACCTTAAAATATTACTACTGGGTTATTAATCCTGCTGA
                 CAGTAGTGGCATTACACCTAAAGGATTAGATGGTCCCCGGCCATCACAAAAAGAAATT
                 ATATCACTGAGGGCATTTATGCTACTTTTTCTGAAACAGCTGATACTAAAGGATCGAG
                 GGGTCAAGGAAGATGAACTTCAGAGTATATTAAATTACCTACTTACGATGCATGAGGA
                 TGAAAATATTCATGATGTGCTACAGTTACTGGTGGCTTTAATGTCGGAACACCCAGCC
                 TCAATGATACCAGCATTTGATCAAAGAAATGGAATAAGGGTGATCTACAAATTATTGG
                 CTTCTAAAAGTGAAAGTATTTGGGTTCAAGCTTTGAAGGTTCTGGGATACTTTCTGAA
                 GCATTTAGGTCACAAGAGAAAAGTTGAAATTATGCACACCCATAGTCTTTTCACTCTT
                 CTTGGAGAAAGGCTGATGTTGCATACAAACACTGTGACTGTCACCACATACAACACAC
                 GCATTTAGGTCACAAGAGAAAAGTTGAAATTATGCACACCCATAGTCTTTTCACTCTT
                 CTTGGAGAAAGGCTGATGTTGCATACAAACACTGTGACTGTCACCACATACAACACAC
                 GCATTTAGGTCACAAGAGAAAAGTTGAAATTATGCACACCCATAGTCTTTTCACTCTT
                 CTTGGAGAAAGGCTGATGTTGCATACAAACACTGTGACTGTCACCACATACAACACAC
                 TTTATGAGATCTTGACAGAACAAGTATGTACTCAGGTCGTACACAAACCACATCCAGA
                 GCCAGATTCTACAGTGAAAATTCAGAATCCAATGATTCTTAAAGTGGTGGCAACTTTG
                 TTAAAAAACTCTACACCAAGTGCAGAGCTGATGGAAGTTCGTCGTTTATTTTTATCTG
                 ATATGATAAAACTTTTCAGTAACAGCCGTGAAAATAGAAGATGCTTATTGCAGTGTTC
                 AGTGTGGCAGGATTGGATGTTTTCTCTTGGCTATATCAATCCTAAAAATTCTGAGGAA
                 CAGAAGATTACCGAAATGGTCTACAATATCTTCCGGATTCTTTTGTATCATGCAATAA
                 AATATGAATGGGGAGGCTGGAGAGTCTGGGTGGATACCCTCTCAATAGCCCATTCCAA
                 GGTCACTTATGAAGCTCATAAGGAATACCTAGCCAAAATGTATGAGGAATATCAAAGA
                 CAAGAGGAGGAAAACATTAAAAAGGGAAAGAAAGGGAATGTGAGCACCATCTCTGGTC
                 TTTCATCACAGACAACAGGAGCAAAAGGTGGAATGGAAATTCGAGAGATAGAAGATCT
                 TTCACAAAGCCAGAGCCCAGAAAGTGAGACCGATTACCCTGTCAGCACAGATACTCGA
                 GACTTACTCATGTCAACAAAAGTGTCAGATGATATTCTTGGAAATTCAGATAGACCAG
                 GAAGTGGTGTACATGTGGAAGTACATGATCTTTTAGTAGATATAAAAGCAGAGAAAGT
                 GGAAGCAACAGAAGTAAAGCTCGATGATATGGATTTATCACCGGAGACTTTAGTAGGT
                 GGAGAGAATGGTGCCCTTGTGGAGGTTGAATCTCTGTTGGATAATGTATATAGTGCTG
                 CTGTTGAGAAACTCCAGAACAATGTACATGGAAGTGTTGGTATCATTAAAAAAAATGA
                 AGAAAAGGATAATGGTCCATTGATAACATTAGCAGATGAGAAAGAAGACCTTCCCAAT
                 AGTAGTACATCATTTCTCTTTGATAAAATACCCAAACAGGAGGAAAAACTACTTCCTG
                 AACTTTCTAGCAATCACATTATTCCAAATATTCAGGACACACAAGTACATCTTGGTGT
                 TAGTGATGATCTTGGATTGCTTGCTCACATGACCGGTAGCGTAGACTTAACTTGTACA
                 TCCAGTATAATAGAAGAAAAAGAATTCAAAATCCATACAACTTCAGATGGAATGAGCA
                 GTATTTCTGAAAGAGACTTAGCGTCATCAACTAAGGGGCTGGAGTATGCTGAAATGAC
                 TGCTACAACTCTGGAAACTGAGTCTTCTAGTAGCAAAATTGTACCAAATATTGATGCA
                 GGAAGTATAATTTCAGATACTGAAAGGTCTGACGATGGCAAAGAATCAGGAAAAGAAA
                 TCCGAAAAATCCAAACAACTACTACGACACAAGGTCGGTCTATCACCCAACAAGACCG
                 AGATCTCCGAGTTGATTTAGGATTTCGAGGAATGCCAATGACTGAGGAACAGCGACGC
                 CAGTTTAGCCCAGGTCCACGGACTACAATGTTTCGTATTCCTGAGTTTAAATGGTCTC
                 CAATGCACCAGCGGCTTCTCACTGATTTACTATTTGCATTAGAAACTGATGTACATGT
                 TTGGAGGAGCCATTCTACAAAGTCTGTAATGGATTTTGTCAATAGCAATGAAAATATT
                 ATTTTTGTACATAACACAATTCACCTCATTTCCCAAATGGTAGACAACATCATCATTG
                 CTTGTGGAGGAATTTTACCTTTGCTCTCTGCTGCTACATCACCAACTGGTTCTAAGAC
                 GGAATTGGAAAATATTGAAGTGACACAAGGCATGTCAGCTGAGACAGCAGTAACTTTC
                 CTCAGCCGGCTGATGGCTATGGTTGATGTACTTGTGTTTGCAAGCTCTCTAAATTTTA
                 GTGAGATTGAAGCTGAGAAAAACATGTCTTCTGGAGGTTTAATGCGACAGTGCCTAAG
                 ATTAGTTTGTTGTGTTGCTGTGAGAAACTGTTTAGAATGTCGGCAAAGACAGAGAGAC
                 AGGGGAAATAAATCTTCCCATGGAAGCAGTAAACCTCAGGAAGTTCCTCAAAGTACTC
                 CATTGGAAAATGTTCCAGGTAACCTTTCTCCTATTAAGGATCCGGATAGACTTCTTCA
                 GGATGTTGATATCAATCGCCTTCGTGCTGTTGTCTTTCGGGATGTGGATGATAGCAAA
                 CAAGCACAGTTCTTAGCTCTGGCTGTTGTTTACTTCATTTCGGTTCTGATGGTTTCCA
                 AGTATCGTGACATATTAGAACCCCAGAGAGAGACTACAAGAACTGGAAGCCAACCAGG
                 TAGAAACATCAGGCAAGAAATAAATTCACCAACAAGTACAGAAACACCTGCTGCATTT
                 CCAGACACCATAAAAGAAAAAGAAACACCAACTCCTGGTGAAGATATTCAGGTAGAAA
                 GTTCAATTCCCCATACAGATTCAGGAATTGGAGAGGAGCAAGTGGCTAGCATCCTGAA
                 TGGGGCAGAATTAGAAACAAGTACAGGCCCTGATGCCATGAGTGAACTCTTATCCACT
                 TTGTCATCCGAAGTGAAGAAATCACAAGAGAGCTTAACTGAAAATCCTAGTGAAACGT
                 AATACTGAAAAGTCTTGTGGCTGCTCCAGTTGAAATAGCAGAATGTGGCCCTGAACCT
                 ATCCCATACCCAGATCCAGCATTGAAGAGAGAAACACAAGCTATTCTTCCTATGCAGT
                 TTCATTCCTTTGACAGCATCACTGCAAAACTTGAAAGAGCGTTAGAAAAAGTTGCTCC
                 TCTTCTTCGTGAAATTTTTGTAGACTTTGCCCCATTCCTATCTCGTACACTTCTTGGC
                 AGTCATGGACAAGAGCTATTGATAGAAGGCCTTGTTTGTATGAAGTCCAGCACATCTG
                 TGGTTGAGCTTGTTATGCTGCTTTGTTCTCAGGAATGGCAAAACTCTATTCAGAAGAA
                 TGCAGGACTTGCATTTATTGAGCTCATCAATGAAGGAAGATTACTGTGCCATGCTATG
                 AAGGACCATATAGTCCGTGTTGCAAATGAAGCTGAGTTTATTTTGAACAGACAAAGAG
                 CCGAGGATGTACATAAACATGCAGAGTTTGAGTCACAGTGTGCCCAATATGCTGCTGA
                 TAGAAGAGAGGAAGAAAAGATGTGTGACCATCTTATCAGTGCTGCTAAACATCGAGAT
                 CATGTAACAGCAAATCAGCTGAAACAGAAGATTCTCAATATTCTCACAAATAAACATG
                 GTGCTTGGGGAGCAGTTTCTCATAGCCAATTGCATGATTTCTGGCGTTTGGATTACTG
                 GGAAGATGATCTTCGTCGAAGGAGACGATTTGTTCGCAATGCATTTGGCTCCACTCAT
                 GCTGAAGCATTGCTGAAAGCTGCAATAGAATATGGCACGGAAGAAGATGTAGTAAAGT
                 CAAAGAAAACATTCAGAAGTCAAGCAATAGTGAACCAAAATGCAGAGACAGAACTTAT
                 GCTGGAAGGAGACGATGATGCAGTCAGTCTGCTACAGGAGAAAGAAATTGACAACCTT
                 GCAGGCCCAGTGGTTCTCAGCACCCCTGCCCAGCTCATCGCTCCCGTGGTGGTGGCCA
                 AGGGGACTCTCTCCATCACCACGACAGAAATCTACTTCGAGGTAGATGAGGATGATTC
                 TGCCTTCAAGAAGATCGACACGAAAGTTCTTGCATACACTGAGGGACTTCACGGAAAA
                 TGGATGTTCAGCGAGATACGAGCTGTATTTTCAAGACGTTACCTTCTACAAAACACTG
                 CTTTGGAAGTATTTATGGCAAACCGAACCTCAGTTATGTTTAATTTCCCTGATCAAGC
                 AACAGTAAAAAAAGTTGTCTATAGCTTGCCTCGGGTTGGAGTAGGGACCAGCTATGGT
                 CTGCCACAAGCCAGGAGGATATCATTGGCCACTCCTCGACAGCTTTATAAATCTTCCA
                 ATATGACTCAGCGCTGGCAAAGAAGGGAAATTTCAAACTTCGAATATTTGATGTTCCT
                 TAATACTATTGCAGGACGGACATATAATGATCTGAACCAATATCCAGTGTTTCCGTGG
                 GTGTTAACCAACTATGAATCAGAAGAGTTGGACCTGACTCTTCCAGGAAACTTCAGGG
                 ATCTATCAAAGCCAATTGGTGCTTTGAACCCCAAGAGAGCTGTGTTTTATGCAGAGCG
                 TTATGAGACATGGGAAGATGATCAAAGCCCACCCTACCATTATAATACCCATTATTCA
                 ACAGCAACATCTACTTTATCCTGGCTTGTTCGAATTGAACCTTTCACAACCTTCTTCC
                 TCAATGCAAATGATGGAAAATTTGATCATCCAGATCGAACCTTCTCATCCGTTGCAAG
                 GTCTTGGAGAACTAGTCAGAGAGATACTTCTGATGTAAAGGAACTAATTCCAGAGTTC
                 TACTACCTACCAGAGATGTTTGTCAACAGTAATGGATATAATCTTGGAGTCAGAGAAG
                 ATGAAGTAGTGGTAAATGATGTTGATCTTCCCCCTTGGGCAAAAAAACCTGAAGACTT
                 TGTGCGGATCAACAGGATGGCCCTAGAAAGTGAATTTGTTTCTTGCCAACTTCATCAG
                 TGGATCGACCTTATATTTGGCTATAAGCAGCGAGGACCAGAAGCAGTTCGTGCTCTGA
                 ATGTTTTTCACTACTTGACTTATGAAGGCTCTGTGAACCTGGATAGTATCACTGATCC
                 TGTGCTCAGGGAGGCCATGGAGGCACAGATACAGAACTTTGGACAGACGCCATCTCAG
                 TTGCTTATTGAGCCACATCCGCCTCGGAGCTCTGCCATGCACCTGTGTTTCCTTCCAC
                 AGAGTCCGCTCATGTTTAAAGATCAGATGCAACAGGATGTGATAATGGTGCTGAAGTT
                 TCCTTCAAATTCTCCAGTAACCCATGTGGCAGCCAACACTCTGCCCCACTTGACCATC
                 CCCGCAGTGGTGACAGTGACTTGCAGCCGACTCTTTGCAGTGAATAGATGGCACAACA
                 CAGTAGGCCTCAGAGGAGCTCCAGGATACTCCTTGGATCAAGCCCACCATCTTCCCAT
                 TGAAATGGATCCATTAATAGCCAATAATTCAGGTGTAAACAAACGGCAGATCACAGAC
                 CTCGTTGACCAGAGTATACAAATCAATGCACATTGTTTTGTGGTAACAGCAGATAATC
                 GCTATATTCTTATCTGTGGATTCTGGGATAAGAGCTTCAGAGTTTATTCTACAGAAAC
                 AGGGAAATTGACTCAGATTGTATTTGGCCATTGGGATGTGGTCACTTGCTTGGCCAGG
                 TCCGAGTCATACATTGGTGGGGACTGCTACATCGTGTCCGGATCTCGAGATGCCACCC
                 TGCTGCTCTGGTACTGGAGTGGGCGGCACCATATCATAGGAGACAACCCTAACAGCAG
                 TGACTATCCGGCACCAAGAGCCGTCCTCACAGGCCATGACCATGAAGTTGTCTGTGTT
                 TCTGTCTGTGCAGAACTTGGGCTTGTTATCAGTGGTGCTAAAGAGGGCCCTTGCCTTG
                 TCCACACCATCACTGGAGATTTGCTGAGAGCCCTTGAAGGACCAGAAAACTGCTTATT
                 CCCACGCTTGATATCTGTCTCCAGCGAAGGCCACTGTATCATATACTATGAACGAGGG
                 CGATTCAGTAATTTCAGCATTAATGGGAAACTTTTGGCTCAAATGGAGATCAATGATT
                 CAACACGGGCCATTCTCCTGAGCAGTGACGGCCAGAACCTGGTCACCGGAGGGGACAA
                 TGGGGTAGTAGAGGTCTGGCAGGCCTGTGACTTCAAGCAACTGTACATTTACCCTGGA
                 TGTGATGCTGGCATTAGAGCAATGGACTTGTCCCATGACCAGAGGACTCTGATCACTG
                 GCATGGCTTCTGGTAGCATTGTAGCTTTTAATATAGATTTTAATCGGTGGCATTATGA
                 GCATCAGAACAGATACAGAAGATAAAGGAAGAACCAAAAGCCAAGTTAAAGCTGAGAG
                 CACAAGTGCTGCATGGAAAGGCAATATCTCTGGTGGAAAAAACTCGTCTACATCGACC
                 TCCGTTTGTACATTCCATCACACCCAGCAATAGCTGTACATTGTAGTCAGCAACCATT
                 TTACTTTGTGTGTTTTTTCACGACTGAACACCAGCTGCTATCAAGCAAGCTTATATCA
                 TGTAAATTATATGAATTAGGAGATGTTTTGGTAATTATTTCATATATTGTTGTTTATT
                 GAGAAAAGGTTGTAGGATGTGTCACAAGAGACTTTTGACAATTCTGAGGAACCTTGTG
                 TCCAGTTGTTACAAAGTTTAAGCTTTGAACCT
                 ORF Start: ATG at 61    ORF Stop: TGA at 8485
                 SEQ ID NO: 50           2808 aa   MW at 314093.6kD
NOV19a.          MASEKPGPGPGLEPQPVGLIAVGAAGGGGGGSGGGGTGGSGMGELRGASGSGSVMLPA
CG132414-01
Protein Sequence GMINPSVPIRNIRMKFAVLIGLIQVGEVSNRDIVETVLNLLVGGEFDLEMNFIIQDAE
                 SITCMTELLEHCDVTCQAEIWSMFTAILRKSVRNLQTSTEVGLIEQVLLKMSAVDDMI
                 ADLLVDMLGVLASYSITVKELKLLFSMLRGESGIWPRHAVKLLSVLNQMPQRHGPDTF
                 FNFPGCSAAAIALPPIAKWPYQNGFTLNTWFRMDPLNNINVDKDKPYLYCFRTSKGVG
                 YSAHFVGNCLIVTSLKSKGKGFQHCVKYDFQPRKWYMISIVHIYNRWRNSEIRCYVNG
                 QLVSYGDMAWHVNTNDSYDKCFLGSSETADANRVFCGQLGAVYVFSEALNPAQIFAIH
                 QLGPGYKSTFKFKSESDIHLAEHHKQVLYDGKLASSIAFTYNAKATDAQLCLESSPKE
                 NASIFVHSPHALMLQDVKAIVTHSIHSAIHSIGGIQVLFPLFAQLDNRQLNDSQVETT
                 VATLLAFLVELLKSSVAMQEQMLGGKGFLVIGYLLEKSSRVHITRAVLEQFLSFAKYL
                 DGLSHGAPLLKQLCDHILFNPAIWIHTPAKVQLSLYTYLSAEFIGTATIYTTIRRVGT
                 VLQLMHTLKYYYWVINPADSSGITPKGLDGPRPSQKEIISLRAFMLLFLKQLILKDRG
                 VKEDELQSILNYLLTMHEDENIHDVLQLLVALMSEHPASMIPAFDQRNGIRVIYKLLA
                 SKSESIWVQALKVLGYFLKHLGHKRKVEIMHTHSLFTLLGERLMLHTNTVTVTTYNTL
                 YEILTEQVCTQVVHKPHPEPDSTVKIQNPMILKVVATLLKNSTPSAELMEVRRLFLSD
                 MIKLFSNSRENRRCLLQCSVWQDWMFSLGYINPKNSEEQKITEMVYNIFRILLYHAIK
                 YEWGGWRVWVDTLSIAHSKVTYEAHKEYKAKMYEEYQRQEEENIKKGKKGNVSTISGL
                 SSQTTGAKGGMEIREIEDLSQSQSPESETDYPVSTDTRDLLMSTKVSDDILGNSDRPG
                 SGVHVEVHDLLVDIKAEKVEATEVKLDDMDLSPETLVGGENGALVEVESLLDNVYSAA
                 VEKLQNNVHGSVGIIKKNEEKDNGPLITLADEKEDLPNSSTSFLFDKIPKQEEKLLPE
                 LSSNHIIPNIQDTQVHLGVSDDLGLLAHMTGSVDLTCTSSIIEEKEFKIHTTSDGMSS
                 ISERDLASSTKGLEYAEMTATTLETESSSSKIVPNIDAGSIISDTERSDDGKESGKEI
                 RKIQTTTTTQGRSITQQDRDLRVDLGFRGMPMTEEQRRQFSPGPRTTMFRIPEFKWSP
                 MHQRLLTDLLFALETDVHVWRSHSTKSVMDFVNSNENIIFVHNTIHLISQMVDNIIIA
                 CGGILPLLSAATSPTGSKTELENIEVTQGMSAETAVTFLSRLMAMVDVLVFASSLNFS
                 EIEAEKNMSSGGLMRQCLRLVCCVAVRNCLECRQRQRDRGNKSSHGSSKPQEVPQSTP
                 LENVPGNLSPIKDPDRLLQDVDINRLRAVVFRDVDDSKQAQFLALAVVYFISVLMVSK
                 YRDILEPQRETTRTGSQPGRNIRQEINSPTSTETPAAFPDTIKEKETPTPGEDIQVES
                 SIPHTDSGIGEEQVASILNGAELETSTGPDAMSELLSTLSSEVKKSQESLTENPSETL
                 KPATSISSISQTKGINVKEILKSLVAAPVEIAECGPEPIPYPDPALKRETQAILPMQF
                 HSFDSITAKLERALEKVAPLLREIFVDFAPFLSRTLLGSHGQELLIEGLVCMKSSTSV
                 VELVMLLCSQEWQNSIQKNAGLAFIELINEGRLLCHAMKDHIVRVANEAEFILNRQRA
                 EDVHKHAEFESQCAQYAADRREEEKMCDHLISAAKHRDHVTANQLKQKILNILTNKHG
                 AWGAVSHSQLHDFWRLDYWEDDLRRRRRFVRNAFGSTHAEALLKAAIEYGTEEDVVKS
                 KKTFRSQAIVNQNAETELMLEGDDDAVSLLQEKEIDNLAGPVVLSTPAQLIAPVVVAK
                 GTLSITTTEIYFEVDEDDSAFKKIDTKVLAYTEGLHGKWMFSEIRAVFSRRYLLQNTA
                 LEVFMANRTSVMFNFPDQATVKKVVYSLPRVGVGTSYGLPQARRISLATPRQLYKSSN
                 MTQRWQRREISNFEYLMFLNTIAGRRYNDLNQYPVFPWVLTNYESEELDLTLPGNFRD
                 LSKPIGALNPKRAVFYAERYETWEDDQSPPYHYNTHYSTATSTLSWLVRIEPFTTFFL
                 LSKPIGALNPKRAVFYAERYETWEDDQSPPYHYNTHYSTATSTLSWLVRIEPFTTFFL
                 NANDGKFDHPDRTFSSVARSWRTSQRDTSDVKELIPEFYYLPEMFVNSNGYNLGVRED
                 EVVVNDVDLPPWAKKPEDFVRINRMALESEFVSCQLHQWIDLIFGYKQRGPEAVRALN
                 VFHYLTYEGSVNLDSITDPVLREAMEAQIQNFGQTPSQLLIEPHPPRSSAMHLCFLPQ
                 SPLMFKDQMQQDVIMVLKFPSNSPVTHVAANTLPHLTIPAVVTVTCSRLFAVNRWHNT
                 VGLRGAPGYSLDQAHHLPIEMDPLIANNSGVNKRQITDLVDQSIQINAHCFVVTADNR
                 YILICGFWDKSFRVYSTETGKLTQIVFGHWDVVTCLARSESYIGGDCYIVSGSRDATL
                 LLWYWSGRHHIIGDNPNSSDYPAPRAVLTGHDHEVVCVSVCAELGLVISGAKEGPCLV
                 HTITGDLLRALEGPENCLFPRLISVSSEGHCIIYYERGRFSNFSINGKLLAQMEINDS
                 TRAILLSSDGQNLVTGGDNGVVEVWQACDFKQLYIYPGCDAGIRAMDLSHDQRTLITG
                 MASGSIVAFNIDFNRWHYEHQNRY

[0420] 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; 0.4000
analysis: probability located in Golgi body; 0.3000 probability
          located in endoplasmic reticulum (membrane); 0.3000
          probability located in microbody (peroxisome)
SignalP   No Known Signal Sequence Predicted
analysis:

[0421] 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
AAY32131	Human LYST-2 protein - Homo	2026 . . . 2808	780/783 (99%)	0.0
	sapiens. 789 a. [WO9951741-A2.	7 . . . 789	782/783 (99%)
	14 OCT. 1999]
AAW23399	Mouse LYST2 polypeptide - Mus	2094 . . . 2791	684/698 (97%)	0.0
	musculus. 703 aa. [WO9728262-	3 . . . 700	692/698 (98%)
	A1.07 AUG. 1997]
AAM39018	Human polypeptide SEQ ID NO	2147 . . . 2808	662/662 (100%)	0.0
	2163- Homo sapiens. 662 aa.	1 . . . 662	662/662 (100%)
	[WO200153312-A1. 26 JUL. 2001]
ABB62664	Drosophila melanogaster	1718 . . . 2808	674/1122 (60%)	0.0
	polypeptide SEQ ID NO 14784-	2511 . . . 3614	856/1122 (76%)
	Drosophila melanogaster. 3614 aa.
	[WO200171042-A2. 27 SEP. 2001]
AAY32120	Human LYST-2 protein - Homo	2290 . . . 2761	470/472 (99%)	0.0
	sapiens 472 aa. [WO9951741-A2.	1 . . . 472	472/472 (99%)
	14 OCT. 1999]

[0422] In a BLAST search of public sequence datbases, the NOV19a protein was found to have homology to the proteins shown in the BLASTP data in Table 19D.

TABLE 19D
Public BLASTP Results for NOV19a
		NOV19a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
AAM53531	BCL8B protein - Homo	1 . . . 1744	1743/1788 (97%)	0.0
	sapiens (Human), 2946 aa.	1 . . . 1788	1743/1788 (97%)
Q9EPN0	Neurobeachin - Mus musculus	1 . . . 1744	1684/1756 (95%)	0.0
	(Mouse), 2904 aa.	1 . . . 1746	1713/1756 (96%)
Q9EPM9	Neurobeachin - Mus musculus	1 . . . 1744	1684/1788 (94%)	0.0
	(Mouse), 2931 aa.	1 . . . 1778	1713/1788 (95%)
Q9EPN1	Neurobeachin - Mus musculus	1 . . . 1744	1684/1788 (94%)	0.0
	(Mouse), 2936 aa.	1 . . . 1778	1713/1788 (95%)
Q9HCM8	KIAA1544 protein - Homo	1781 . . . 2808	1028/1028 (100%)	0.0
	sapiens (Human), 1028 aa	1 . . . 1028	1028/1028 (100%)
	(fragment).

[0423] PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19E.

TABLE 19E
Domain Analysis of NOV19a
		Identities/
		Similarities
	NOV19a	for the	Expect
Pfam Domain	Match Region	Matched Region	Value
Beach	2148 . . . 2425	182/287 (63%)	4.9e−208
		260/287 (91%)
WD40	2717 . . . 2752	11/37 (30%)	0.89
		29/37 (78%)

Example 20

[0424] 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: 51           2687 bp
NOV20a.          ACAAGCTCCACAGAGCCGCGGGAGGACGGTTGCCTGGTATTATTAGCAAGCAGCAAAT
CG133140-01
DNA Sequence     ATGGCGGTGGCGCGCGTGGACGCGGCTTTGCCTCCCGGAGAAGGTTCAGTGGTCAATT
                 GGTCAGGACAGGGACTACAGAAATTAGGTCCAAATTTACCCTGTGAAGCTGATATTCA
                 CACTTTGATTCTGGATAAAAATCAGATTATTAAATTGGAAAATCTGGAGAAATGCAAA
                 CGATTAATACAGTTATCAGTAGCTAATAATCGGCTGGTTCGGATGATGGGTGTGGCCA
                 AGCTGACGTTGCTTCGTGTATTAAATTTGCCTCATAATAGCATTGGCTGTGTGGAAGG
                 GCTAAAGGAACTAGTACATCTGGAATGGCTGAATTTGGCAGGAAATAATCTTAAGGCC
                 ATGGAACAGATCAATAGCTGCACAGCTCTACAGCATCTCGATTTATCAGACAATAATA
                 TATCCCAGATAGGTGATCTATCTAAATTGGTATCCCTGAAAGTAAAGACCCTGCTTTT
                 ACATGGAAACATCATCACCTCTCTTAGAATGGCACCTGCTTACCTACCCAGAAGTCTT
                 GCTATACTTTCTTTGGCAGAAAATGAAATCCGAGACTTAAATGAGATCTCTTTTTTGG
                 CATCCTTAACTGAATTGGAACAGTTGTCGATTATGAACAATCCTTGTGTGATGGCAAC
                 ACCATCCATCCCAGGATTTGACTATCGGCCGTACATCGTCAGCTGGTGCCTAAACCTC
                 AGAGTCCTAGATGGATATGTGATTTCTCAGAAGGAAAGTTTGAAAGCTGAATGGCTCT
                 ATAGTCAAGGCAAGGGGAGAGCATATCGGCCTGGCCAGCACATCCAGCTTGTCCAATA
                 TCTGGCTACAGTCTGCCCCCTCACTTCTACACTAGGTCTTCAAACTGCAGAGGATGCC
                 AAACTAGACAAGATTTTGAGCAAACAGAGGTTTCACCAGAGGCAGTTGATGAACCAAA
                 GCCAAAATGAAGAGTTGTCTCCTCTTGTTCCTGTTGAAACAAGGGCATCCCTTATTCC
                 TGAGCATTCAAGCCCTGTTCAAGATTGCCAGATATCCGAACCCGTCATTCAAGTGAAT
                 TCTTGGGTTGGGATAAACAGTAATGATGATCAGTTATTTGCGGTTAAGAATAATTTTC
                 CAGCCTCTAGTCACACTACGAGATATTCTCGAAATGATCTGCACCTGGAAGACATACA
                 GACGGATGAGGACAAGTTAAACTGTAGTCTTCTCTCTTCAGAGTCTACTTTTATGCCA
                 GTTGCATCAGGACTGTCTCCACTATCACCTACAGTTGAGCTGAGGCTGCAGGGCATTA
                 ACTTGGGCCTAGAAGATGATGGTGTTGCAGATGAATCTGTGAAAGGGCTGGAAAGCCA
                 GGTGTTGGATAAGGAAGAGGAACAGCCTTTATGGGCTGCAAATGAGAATTCTGTTCAA
                 ATGATGAGAAGTGAAATCAATACAGAGGTAAATGAGAAAGCTGGACTATTACCTTGTC
                 GGTGTTGGATAAGGAAGAGGAACAGCCTTTATGGGCTGCAAATGAGAATTCTGTTCAA
                 ATGATGAGAAGTGAAATCAATACAGAGGTAAATGAGAAAGCTGGACTATTACCTTGTC
                 CTGAGCCAACAATAATCAGTGCTATCTTGAAGGATGATAACCACAGTCTTACATTTTT
                 TCCTGAGTCAACTGAGCAGAAACAATCAGACATAAAGAAACCAGAAAATACACAACCA
                 GAAAATAAAGAAACCATATCTCAAGCAACTTCAGAGAAACTTCCCATGATTTTAACCC
                 AGAGATCTGTTGCTTTGGGACAAGACAAAGTTGCCCTTCAGAAATTAAATGATGCAGC
                 CACCAAGCTTCAGGCCTGTTGGCGGGGATTTTATGCCAGGAACTACAACCCTCAAGCC
                 AAAGATGTGCGTTACGAAATCCGGCTACGCAGAATGCAAGAGCACATTGTCTGCTTAA
                 CTGATGAAATAAGGAGATTACGAAAAGAAAGAGATGAAGAACGTATTAAAAAATTTGT
                 ACAAGAAGAAGCTTTCAGATTCCTTTGGAACCAGGTAAGGTCTCTACAGGTTTGGCAA
                 CAGACAGTGGACCAGCGTCTAAGTTCCTGGCATACTGATGTTCAACAAATATCAAGTA
                 CTCTTGTGCCATCGAAACATCCATTATTTACCCAAAGCCAGGAGTCCTCTTGTGATCA
                 AAATGCTGATTGGTTTATTGCTTCTGATGTAGCTCCTCAAGAGAAATCATTACCAGAA
                 TTTCCAGACTCTGGTTTTCATTCCTCTCTAACAGAACAAGTTCATTCATTGCAGCATT
                 CTTTGGATTTTGAGAAAAGTTCCACAGAAGGCAGTGAAAGCTCCATAATGGGGAATTC
                 CATTGACACAGTCAGATATGGCAAACAATCAGATTTAGGGGATGTTAGTGAAGAACAT
                 GGTGAATGGAATAAGGAAAGCTCAAATAACGAGCAGGACAATAGTCTGCTTGAACAGT
                 ATTTAACTTCAGTTCAACAGCTGGAAGATGCTGATGAGAGGACCAATTTTGATACAGA
                 GACAAGAGATAGCAAACTTCACATTGCTTGTTTCCCAGTACAGTTAGATACATTGTCT
                 GACGGTGCTTCTGTAGATGAGAGTCATGGCATATCTCCTCCTTTGCAAGGTGAAATTA
                 GCCAGACACAAGAGAATTCTAAATTAAATGCAGAAGTTCAGGGGCAGCAGCCAGAATG
                 TGATTCTACATTTCAGCTATTGCATGTTGGTGTTACTGTGTAGCATGTCTTTTGGGAG
                 GCAGATATCCACTTAACTT
                 ORF Start ATG at 59     ORF Stop: TAG at 265
                 SEQ ID NO: 52           864 aa    MW at 96898.9kD
NOV20a.          MAVARVDAALPPGEGSVVNWSGQGLQKLGPNLPCEADIHTLILDKNQIIKLENLEKCK
CC133140-0
Protein Sequence RLIQLSVANNRLVRMMGVAKLTLLRVLNLPHNSIGCVEGLKELVHLEWLNLAGNNLKA
                 MEQINSCTALQHLDLSDNNISQIGDLSKLVSLKVKTLLLHGNIITSLRMAPAYLPRSL
                 AILSLAENEIRDLNEISFLASLTELEQLSIMNNPCVMATPSIPGFDYRPYIVSWCLNL
                 RVLDGYVISQKESLKAEWLYSQGKGRAYRPGQHIQLVQYLATVCPLTSTLGLQTAEDA
                 KLDKILSKQRFHQRQLMNQSQNEELSPLVPVETRASLIPEHSSPVQDCQISEPVIQVN
                 SWVGINSNDDQLFAVKNNFPASSHTTRYSRNDLHLEDIQTDEDKLNCSLLSSESTFMP
                 VASGLSPLSPTVELRLQGINLGLEDDGVADESVKGLESQVLDKEEEQPLWAANENSVQ
                 MMRSEINTEVNEKAGLLPCPEPTIISAILKDDNHSLTFFPESTEQKQSDIKKPENTQP
                 ENKETISQATSEKLPMILTQRSVALGQDKVALQKLNDAATKLQACWRGFYARNYNPQA
                 KDVRYEIRLRRMQEHIVCLTDEIRRLRKERDEERIKKFVQEEAFRFLWNQVRSLQVWQ
                 QTVDQRLSSWHTDVQQISSTLVPSKHPLFTQSQESSCDQNATWFIASDVAPQEKSLPE
                 FPDSGFHSSLTEQVHSLQHSLDFEKSSTEGSESSIMGNSIDTVRYGKESDLGDVSEER
                 GEWNKESSNNEQDNSLLEQYLTSVQQLEDADERTNFDTETRDSKLHIACFPVQLDTLS
                 DGASVDESHGISPPLQGEISQTQENSKLNAEVQGQQPECDSTFQLLHVGVTV

[0425] Further analysis of the NOV20a protein yielded the following properties shown in Table 20B.

TABLE 20B
Protein Sequence Properties NOV20a
PSort     0.4500 probability located in cytoplasm; 0.3000
analysis: probability located in microbody (peroxisome); 0.1000
          probability located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0426] A search of the NOV20a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 20C.

TABLE 20C
Geneseq Results for NOV20a
		NOV20a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length[Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
ABB60319	Drosophila melanocaster	14 . . . 636	206/648 (31%)	e−77
	polypeptide SEQ ID NO 7749 -	9 . . . 625	330/648 (50%)
	Drosophila melanogaster. 774 aa.
	[WO200171042-A2. 27 SEP. 2001]
AAM25487	Human protein sequence SEQ ID	1 . . . 129	128/129 (99%)	5e−68
	NO:1002 - Homo sapiens. 133 aa.	5 . . . 133	128/129 (99%)
	[WO200153455-A2. 26 JUL. 2001]
AAG03667	Human secreted protein. SEQ ID	1 . . . 129	127/129 (98%)	3e−67
	NO: 7748- Homo sapiens. 129 aa.	1 . . . 129	127/129 (98%)
	[EP1033401-A2. 06 SEP. 2000]
AAY12286	Human 5′ EST secreted protein SEQ	73 . . . 130	57/58 (98%)	6e−26
	ID NO:317 - Homo sapiens. 58 aa.	1 . . . 58	57/58 (98%)
	[WO9906548-A2. 11 FEB. 1999]
ABG12142	Novel human diagnostic protein	189 . . . 245	56/57 (98%)	1e−25
	#12133 - Homo sapiens. 422 aa.	109 . . . 165	57/57 (99%)
	[WO200175067-A2. 11 OCT. 200I]

[0427] In a BLAST search of public sequence datbases, the NOV20a protein was found to have homology to the proteins shown in the BLASTP data in Table 20D.

TABLE 20D
Public BLASTP Results for NOV20a
		NOV20a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9CZ62	2810403B08Rik protein - Mus	1 . . . 864	658/865 (76%)	0.0
	musculus (Mouse), 856 aa.	1 . . . 853	729/865 (84%)
Q9VQV7	CG3980 protein - Drosophila	14 . . . 636	206/648 (31%)	4e−77
	melanogaster (Fruit fly), 774 aa.	9 . . . 625	330/648 (50%)
Q9H5T9	CDNA: FLJ23047 fis, clone	732 . . . 864	132/133 (99%)	4e−69
	LNG02513 - Homo sapiens	1 . . . 132	132/133 (99%)
	(Human), 132 aa.
O16366	R02F11.4 protein -	60 . . . 300	72/242 (29%)	1e−20
	Caenorhabditis elegans, 630 aa.	122 . . . 336	113/242 (45%)
Q09589	Hypothetical 136.6 kDa protein -	34 . . . 207	59/174 (33%)	1e−14
	Caenorhabditis elegans, 1223 aa.	30 . . . 196	91/174 (51%)

[0428] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20E.

TABLE 20E
Domain Analysis of NOV20a
		Identities/
		Similarities
	NOV20a	for the	Expect
Pfam Domain	Match Region	Matched Region	Value
LRR	125 . . . 146	9/25 (36%)	0.0098
		19/25 (76%)
IQ	558 . . . 578	10/21 (48%)	0.05
		16/21 (76%)

Example 21

[0429] 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: 53           3222 bp
NOV21a.          TTCAGCCCTGAGAATTTTGAGCCACATTTGTTGCTATTATTTTTGCATGCACTTTTCA
CG133369-01
DNA Sequence     AAATGATTGACTTAAGCTTCCTGACTGAAGAGGAACAAGAGGCCATCATGAAGGTTTT
                 GCAGCGGGATGCTGCTCTGAAGAGGGCCGAAGAAGAGAGAGTCAGACATTTGCCTGAA
                 AAAATTAAGGATGACCAGCAGCTGAAGAATATGAGTGGCCAATGGTTTTATGAAGCCA
                 AGGCAAAAAGGCACAGGGACAAAATCCATGGCGCAGATATCATCAGAGCATCTATGAG
                 AAAGAAGAGGCCCCAGATAGCAGCTGAGCAGAGTAAAGACAGAGAAAATGGGGCAAAG
                 GAAAGCTGGGTGAATAATGTCAACAAAGATGCTTTCCTTCCTCCAGAGCTGGCTGGCG
                 TTGTAGAAGAGCCAGAAGAAGATGCAGCACCAGCAAGCCCGAGTTCCAGTGTGGTAAA
                 TCCAGCTTCCAGTGTGATTGATATGTCCCAGGAAAACACAAGGAAACCAAATGTGTCT
                 CCAGAGAAGCAGAGGAAGAATCCGTTTAATAGCTCCAAGTTGCCAGAAGGTCACTCAT
                 CACAACAAACTAAAAATGAACAGTCAAAAAATGGAAGAACTGGTTTATTTCAGACTTC
                 AAAAGAGGATGAATTGTCAGAGTCAAAAGAAAAGTCAACTGTCGCAGATACTTCAATC
                 CAAAAGTTAGAGAAATCAAAGCAGACTTTGCCAGGCCTTTCAAATGGGTCCCAAATCA
                 AGGCTCCAATCCCCAAAGCCAGGAAGATGATCTACAAATCAACTGATTTAAACAAAGA
                 TGATAACCAGTCTTTTCCTAGACAAAGGACAGACTCCCTGAAAGCGAGAGGGGCTCCG
                 AGAGGGATCCTCAAGCGCAACTCCAGTTCCAGTAGCACAGACTCAGAAACCCTTCGTT
                 ATAATCACAACTTTGAACCCAAAAGCAAAATTGTGTCACCTGGCCTAACCATCCATGA
                 GAGAATTTCTGAGAAGGAGCATTCTTTAGAAGACAACTCTTCCCCAAACTCCCTGGAG
                 CCATTAAAGCATGTGAGATTCTCTGCAGTGAAGGATGAGCTTCCACAGAGTCCTGGGC
                 TAATCCATGGTCGGGAAGTAGGAGAATTTAGTGTTTTAGAATCTGACAGATTGAAAAA
                 TGGAATGGAAGATGCAGGGGACACAGAAGAGTTTCAGAGTGACCCTAAGCCTTCTCAA
                 TACAGAAAGCCTTCGCTTTTTCATCAATCAACCTCAAGCCCATATGTATCAAAAAGTG
                 AAACACATCAGCCAATGACTTCTGGTTCTTTTCCAATTAATGGGCTGCATTCTCATTC
                 AGAAGTTTTAACTGCAAGACCACAGTCTATGGAGAATTCACCAACCATCAATGAACCC
                 AAAGATAAATCATCAGAATTAACAAGGCTTGAATCTGTATTACCCAGAAGCCCTGCTG
                 ATGAACTGTCTCATTGTGTTGAGCCTGAGCCATCTCAGGTGCCAGGTGGCAGTTCTAG
                 AGACCGTCAGCAAGGTTCAGAAGAAGAACCCAGTCCTGTTTTGAAAACTTTGGAAAGG
                 AGTGCCGCTAGGAAAATGCCTTCCAAAAGTCTAGAAGACATTTCATCAGATTCATCAA
                 ATCAAGCAAAAGTAGATAATCAGCCAGAAGAATTAGTGCGTAGTGCTGAAGATGATGA
                 GAAACCAGATCAGAAGCCAGTTACAAATGAATGCGTACCAAGAATTTCCACAGTGCCT
                 ACACAACCTGATAATCCATTTTCTCACCCTGACAAACTCAAAAGGATGAGCAAGTCTG
                 TTCCAGCATTTCTCCAAGATGAGGCAGATGACAGAGAAACAGATACAGCATCAGAAAG
                 CAGTTACCAGCTCAGCAGACACAAGAAGAGCCCGAGCTCTTTAACCAATCTTAGCAGC
                 TCCTCTGGCATGACGTCCTTGTCTTCTGTGAGTGGCAGTGTGATGAGTGTTTATAGTG
                 GAGACTTTGGCAATCTGGAAGTTAAAGGAAATATTCAGTTTGCAATTGAATATGTGGA
                 GTCACTGAAGGAGTTGCATGTTTTTGTGGCCCAGTGTAACGACTTAGCAGCAGCGGAT
                 GTAAAAAAACAGCGTTCAGACCCATATGTAAAGGCCTATTTGCTACCAGACAAAGGCA
                 AAATGGGCAAGAAGAAAACACTCGTAGTGAAGAAAACCTTGAATCCTGTGTATAACGA
                 AATACTGCGGTATAAAATTGAAAAACAAATCTTAAAGACACAGAAATTGAACCTGTCC
                 ATTTGGCATCGGGATACATTTAAGCGCAATAGTTTCCTAGGGGAGGTGGAACTTGATT
                 TGGAAACATGGGACTGGGATAACAAACAGAATAAACAATTGAGATGGTACCCTCTGAA
                 GCGGAAGACAGCACCAGTTGCCCTTGAAGCAGAAAACAGAGGTGAAATGAAACTAGCT
                 CTCCAGTATGTCCCAGAGCCAGTCCCTGGTAAAAAGCTTCCTACAACTGGAGAAGTGC
                 ACATCTGGGTGAAGGAATGCCTTGATCTACCACTGCTAAGGGGAAGTCATCTAAATTC
                 TTTTGTTAAATGTACCATCCTTCCAGATACAAGTAGGAAAAGTCGCCAGAAGACAAGA
                 GCTGTAGGGAAAACCACCAACCCTATCTTCAACCACACTATGGTGTATGATGGGTTCA
                 GGCCTGAAGATCTGATGGAAGCCTGTGTAGAGCTTACTGTCTGGGACCATTACAAATT
                 AACCAACCAATTTTTGGGAGGTCTTCGTATTGGCTTTGGAACAGGTAAAAGTTATGGG
                 ACTGAAGTGGACTGGATGGACTCTACTTCAGAGGAAGTTGCTCTCTGGGAGAAGATGG
                 TAAACTCCCCCAATACTTGGATTGAAGCAACACTGCCTCTCAGAATGCTTTTGATTGC
                 CAAGATTTCCAAATCAGCCCAAATTCCATCTGGCTCCTCCACTGAAAACTACTAAACCG
                 GTGGAATCTGATCTTGAAAATCTGAGTAGGTGGACAAATATCCTCACTTTCTATCTAT
                 TGCACCTAAGGAATACTACACAGCATGTAAAAGTCAATCTGCATGTGCTTCTTTGATT
                 ACAAGGCCCAAGGGATTTAAATATAACAAAATGTGTAATTTGTGACTCTAATATTAAA
                 TAAGATATTTGAACAAGCTAGGAAAATTGAATTTCTGCTGCTGCTTCAAAGAAAAAGC
                 TGCCCCAGAGCATTAAACATGGGGTATTGTTA
                 ORF Start: ATG at 61    ORF Stop: TGA at 2914
                 SEQ ID NO 54            951 aa    MW at 106892.0kD
NOV21a.          MIDLSFLTEEEQEAIMKVLQRDAALKRAEEERVRHLPEKIKDDQQLKNMSGQWFYEAK
CG133369-01
Protein Sequence AKRHRDKIHGADIIRASMRKKRPQIAAEQSKDRENGAKESWVNNVNKDAFLPPELAGV
                 VEEPEEDAAPASPSSSVVNPASSVIDMSQENTRKPNVSPEKQRKNPFNSSKLPEGHSS
                 QQTKNEQSKNGRTGLFQTSKEDELSESKEKSTVADTSIQKLEKSKQTLPGLSNGSQIK
                 APIPKARKMIYKSTDLNKDDNQSRPRQRTDSLKARGAPRGILKRNSSSSSTDSETLRY
                 NHNFEPKSKIVSPGLTIHERISEKEHSLEDNSSPNSLEPLKHVRFSAVKDELPQSPGL
                 THGREVGEFSVLESDRLKNGMEDAGDTEEFQSDPKPSQYRKPSLFHQSTSSPYVSKSE
                 THQPMTSGSFPINGLHSHSEVLTARPQSMENSPTINEPKDKSSELTRLESVLPRSPAD
                 ELSHCVEPEPSQVPGGSSRDRQQGSEEEPSPVLKTLERSAARKMPSKSLEDISSDSSN
                 QAKVDNQPEELVRSAEDDEKPDQKPVTNECVPRISTVPTQPDNPFSHPDKLKRMSKSV
                 PAFLQDEADDRETDTASESSYQLSRHKKSPSSLTNLSSSSGMTSLSSVSGSVMSVYSG
                 DFGNLEVKGNIQFAIEYVESLKELHVFVAQCKDLAAADVKKQRSDPYVKAYLLPDKGK
                 MGKKKTLVVKKTLNPVYNEILRYKEIKQILKTQKLNLSIWHRDTFKRNSFLGEVELDL
                 ETWDWDNKQNKQLRWYPLKRKTAPVALEAENRGEMKLALQYVPEPVPGKKLPTTGEVH
                 IWVKECLDLPLLRGSHLNSFVKCTILPDTSRKSRQKTRAVGKTTNPIFNHTMVYDGFR
                 PEDLMEACVELTVWDHYKLTNQFLGGLRIGFGTGKSYGTEVDWMDSTSEEVALWEKMV
                 NSPNTWIEATLPLRMLLIAKISK

[0430] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.

TABLE 21B
Protein Sequence Properties NOV21a
PSort     0.7000 probability located in nucleus; 0.3000 probability
analysis: located in microbody (peroxisome); 0.1000 probability
          located in mitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0431] 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/Organisim/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB11731	Human granuphilin-a homologue,	521..951	410/431 (95%)	0.0
	SEQ ID NO 2101—Homo sapiens,	1..415	415/431 (96%)
	415 aa. [WO200157188-A2, 09-
	AUG-2001]
AAU19725	Human novel extracellular matrix	522..951	390/430 (90%)	0.0
	protein, Seq ID No 375—Homo	18..407	390/430(90%)
	sapiens, 407 aa. [WO200155368-
	A1, 02-AUG-2001]
AAM93772	Human polypeptide, SEQ ID NO:	576..951	375/376 (99%)	0.0
	3778—Homo sapiens, 376 aa.	1..376	376/376 (99%)
	[EP1130094-A2, 05-SEP-2001]
AAU87550	Novel central nervous system	626..951	326/326 (100%)	0.0
	protein #460—Homo sapiens, 348	23..348	326/326 (100%)
	aa. [WO200155318-A2, 02-AUG-
	2001]
AAU19852	Human novel extracellular matrix	626..951	326/326 (100%)	0.0
	protein, Seq ID No 502—Homo	23..348	326/326 (100%)
	sapiens, 348 aa. [WO200155368-
	A1, 02-AUG-2001]

[0432] In a BLAST search of public sequence datbases, the NOV21a protein was found to have homology to the proteins shown in the BLASTP data in Table 21D.

TABLE 21D
Public BLASTP Results for NOV21a
			Identities/
		NOV21a	Similarities
Protein		Residues/	for the
Accession		Match	Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9HCH5	KIAA1597 protein - Homo sapiens (Human).	13 . . . 951	897/939 (95%)	0.0
	913 aa (fragment).	16 . . . 913	897/939 (95%)
Q99N56	Synaptotagmin-like protein 2-a -	1 . . . 951	781/952 (82%)	0.0
	Mus musculus (Mouse). 950 aa.	1 . . . 950	845/952 (88%)
Q99N51	Synaptotagmin-like protein 2-a delta	1 . . . 951	770/952 (80%)	0.0
	2S-II - Mus musculus (Mouse). 934 aa.	1 . . . 934	832/952 (86%)
Q99N52	Synaptotagmin-like protein 2-a delta	1 . . . 951	759/952 (79%)	0.0
	2S-I - Mus musculus (Mouse). 923 aa.	1 . . . 923	821/952 (85%)
Q9NXMI	CDNA FLJ20I63 fis. clone COL09380 -	1 . . . 463	462/463 (99%)	0.0
	Homo sapiens (Human). 471 aa.	1 . . . 462	462/463 (99%)

[0433] PFam analysis predicts that the NOV21a protein contains the domains shown in the Table 21E.

TABLE 21E
Domain Analysis of NOV21a
		Identities/
		Similarities
	NOV21a	for the	Expect
Pfam Domain	Match Region	Matched Region	Value
C2	662 . . . 751	38/97 (39%)	8.2e−21
		65/97 (67%)
C2	811 . . . 898	23/97 (24%)	4.2e−11
		65/97 (67%)

Example 22

[0434] 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: 55	2478 bp
NOV22a,	ACTAGTAAAAAAAGAAAAAGAAAAAATAAAGTGAAAGAGGCGTGTTGTCTAGTTTCAA
CG133456-01
DNA Sequence	AGGAGAGGAGAGAAGGCAACTCTGGTAGCTCTCCTTGTCTCGTTGTTTTGAAGAAAGA
	AGAGTAGAAGAAAAAGTTGAGTAAATCATGTCGGAGTTACTGGACCTTTCTTTTCTGT
	CTGAGGAGGAAAAGGATTTGATTCTCAGTGTTCTACAGCGAGATGAAGAGGTCCGGAA
	AGCAGATGAGAAAAGGATTAGGCGACTAAAGAATGAGTTACTGGAGATAAAAAGGAAA
	GGGGCCAAGAGGGGCAGCCAACACTACAGTGATCGGACCTGTGCCCGGTGCCAGGAGA
	GCCTGGGCCGTTTGAGTCCCAAAACCAATACTTGTCGGGGTTGTAATCACCTGGTGTG
	TCGGGACTGCCGCATACAGGAAAGCAATGGTACCTGGAGGTGCAAGGTGTGCGCCAAG
	GAAATAGAGTTGAAGAAAGCAACTGGGGACTGGTTTTATGACCAGAAAGTGAATCGCT
	TTGCTTACCGCACAGGTAGTGAGATAATCAGGATGTCCCTGCGCCACAAACCTGCAGT
	GAGTAAAAGAGAGACAGTGGGACAGTCCCTCCTTCATCAGACACAGATGGGTGACATC
	TGGCCAGGAAGAAAGATCATTCAGGAGCGGCAGAAGGAGCCCAGTGTGCTATTTGAAG
	TGCCAAAGCTGAAAAGTGGAAAGAGTGCATTGGAAGCTGAGAGTGAGAGTCTGGATAG
	CTTCACAGCTGACTCGGATAGCACCTCCAGGAGAGACTCTCTGGATAAATCTGGCCTC
	TTTCCAGAATGGAAGAAGATGTCTGCTCCCAAATCTCAAGTAGAAAAGGAAACTCAGC
	CTGGAGGTCAAAATGTGGTATTTGTGGATGAGGGTGAGATGATATTTAAGAAGAACAC
	CAGAAAAATCCTCAGGCCTTCAGAGTACACTAAATCTGTGATAGATCTTCGCCCAGAA
	GATGTGGTACATGAAAGTGGCTCCTTGGGAGACAGAAGCAAATCCGTCCCAGGCCTCA
	ATGTGGATATGGAAGAGGAAGAAGAAGAAGAAGACATTGACCACCTAGTGAAGTTACA
	TCGCCAGAAGCTAGCCAGAAGCAGCATGCAAAGTGGCTCCTCCATGAGTACGATCGGC
	AGCATGATGAGCATCTACAGTGAAGCTGGTGATTTCGGGAACATCTTTGTGACTGGCA
	GGATTGCCTTTTCCCTGAAGTATGAGCAGCAAACCCAGAGTCTGGTTGTCCATGTGAA
	GGAGTGCCATCAGCTGGCCTATGCTGATGAAGCCAAGAAGCGCTCTAACCCATATGTG
	AAGACTTACCTTCTGCCTGACAAGTCCCGCCAAGGAAAAAGAAAAACCAGCATCAAGC
	GGGACACTATTAATCCACTATATGATGAGACGCTGAGGTATGAGATCCCAGAATCTCT
	CCTGGCCCAGAGGACCCTGCAGTTCTCAGTTTGGCATCATGGTCGTTTTGGCAGAAAC
	ACTTTCCTTGGAGAGGCAGAGATCCAGATGGATTCCTGGAAGCTTGATAAGAAACTGG
	ATCATTGCCTCCCTTTACATGGAAAGATCAGTGCTGAGTCCCCGACTGGCTTGCCATC
	ACACAAAGGCGAGTTGGTGGTTTCATTGAAATACATCCCAGCCTCCAAAACCCCTGTT
	GGAGGTGACCGGAAAAAGAGTAAAGGTGGGGAAGGGGGAGAGCTCCAGGTGTGGATCA
	AAGAAGCCAAGAACTTGACGGCTGCCAAAGCAGGAGGGACTTCAGACAGCTTTGTCAA
	GGGATACCTCCTTCCCATGAGGAACAAGGCCAGTAAACGTAAAACTCCTGTGATGAAG
	AAGACCCTGAATCCTCACTACAACCATACATTTGTCTACAATGGTGTGAGGCTGGAAG
	ATCTACAGCATATGTGCCTGGAACTGACTGTGTGGGACCGGGAGCCCCTGGCCAGCAA
	TGACTTCCTGGGAGGGGTCAGGCTGGGTGTTGGCACTGGGATCAGTAATGGGGAAGTG
	GTGGACTGGATGGACTCGACTGGGGAAGAAGTGAGCCTGTGGCAGAAGATGCGACAGT
	ACCCAGGGTCTTGGGCAGAAGGGACTCTGCAGCTCCGTTCCTCAATGGCCAAGCAGAA
	GCTGGGTTTATGAGTCCCTGTCCTCTTCTGCAGGTCCAGCCCTGGCGAGGGCAGGTCA
	GAGGAAGTGAAGAAATCAAGAGCAAAGATTTATAATTTAATGTGTATGTGTGTATGTG
	TGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTACAAACATGTATTTTCTGCAAAT
	CTCATTATGCTGGCTAGAGTGATGCAGACTTGTTCTTCTTTTTAAAGCAGTCTCAAGA
	ATAAGCATTTCTTTAAAATGTTTCTGTGTATAATCTAGTTTATTTTCAGAGTCCATTT
	TTTCTTATGTCTTTATAAGGTTCACTTAACTTAAAAACAGT
	ORF Start: ATG at 144	ORF Stop: TGA at 2157
	SEQ ID NO: 56	671 aa	MW at 76022.8kD
NOV22a	MSELLDLSFLSEEEKDLILSVLQRDEEVRKADEKRIRRLKNELLEIKRKGAKRGSQHY
CG133456-01
Protein Sequence	SDRTCARCQESLGRLSPKTNTCRGCNHLVCRDCRIQESNGTWRCKVCAKEIELKKATG
	DWFYDQKVNRFAYRTGSEIIRMSLRHKPAVSKRETVGQSLLHQTQMGDIWPGRKIIQE
	RQKEPSVLFEVPKLKSGKSALEAESESLDSFTADSDSTSRRDSLDKSGLFPEWKKMSA
	PKSQVEKETQPGGQNVVFVDEGEMIFKKNTRKILRPSEYTKSVIDLRPEDVVHESGSL
	GDRSKSVPGLNVDMEEEEEEEDIDHLVKLHRQKLARSSMQSGSSMSTIGSMMSIYSEA
	GDFGNIFVTGRIAFSLKYEQQTQSLVVHVKECHQLAYADEAKKRSNPYVKTYLLPDKS
	RQGKRKTSIKRDTINPLYDETLRYEIPESLLAQRTLQFSVWHHGRFGRNTFLGEAEIQ
	MDSWKLDKKLDHCLPLHGKISAESPTGLPSHKGELVVSLKYIPASKTPVGGDRKKSKG
	GEGGELQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLNPHYNH
	TFVYNGVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGVGTGISNGEVVDWMDSTGE
	EVSLWQKMRQYPGSWAEGTLQLRSSMAKQKLGL

[0435] Further analysis of the NOV22a protein yielded the following properties shown in Table 22B.

TABLE 22B
Protein Sequence Properties NOV22a
PSort     0.8800 probability located in nucleus; 0.1000 probability
analysis: located in mitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen); 0.0000 probability located
          in endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0436] 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 22G
Geneseq Results for NOV22a
		NOV22a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organisim/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAE17496	Human secretion and trafficking	1..671	670/671 (99%)	0.0
	protein-5 (SAT-5)—Homo sapiens,	1..671	671/671 (99%)
	671 aa. [WO200202610-A2, 10-
	JAN-2002]
AAU87541	Novel central nervous system	378..603	224/226 (99%)	e−132
	protein #451—Homo sapiens, 234	2..227	226/226 (99%)
	aa. [WO200155318-A2, 02-AUG-
	2001]
AAU87238	Novel central nervous system	378..603	224/226(99%)	e−132
	protein #148—Homo sapiens, 234	2..227	226/226 (99%)
	aa. [WO200155318-A2, 02-AUG-
	2001]
AAU19717	Human novel extracellular matrix	378..603	224/226 (99%)	e−132
	protein, Seq ID No 367—Homo	2..227	226/226 (99%)
	sapiens, 234 aa. [WO200155368-
	A1, 02-AUG-2001]
AAM94291	Human reproductive system related	378..603	224/226 (99%)	e−132
	antigen SEQ ID N0: 2949—Homo	2..227	226/226 (99%)
	sapiens, 234 aa. [WO200155320-
	A2, 02-AUG-2001]

[0437] In a BLAST search of public sequence datbases, the NOV22a protein was found to have homology to the proteins shown in the BLASTP data in Table 22D.

TABLE 22D
Public BLASTP Results for NOV22a
		NOV22a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96C24	Similar to synaptotagmin-like 4 -	1 . . . 671	670/671 (99%)	0.0
	Homo sapiens (Human), 671 aa.	1 . . . 671	671/671 (99%)
Q8VHQ7	Granuphilin A - Rattus norvegicus	1 . . . 671	615/672 (91%)	0.0
	(Rat), 672 aa.	1 . . . 672	643/672 (95%)
Q9R0Q1	Granuphilin-a - Mus musculus	1 . . . 671	608/673 (90%)	0.0
	(Mouse), 673 aa.	1 . . . 673	640/673 (94%)
Q9H4R1	BA524D16A.2.1 (Novel protein	181 . . . 671	491/491 (100%)	0.0
	similar to mouse granuphilin-a) -	1 . . . 491	491/491 (100%)
	Homo sapiens (Human), 491 aa
	(fragment).
Q8VHQ6	Granuphilin B - Rattus norvegicus	1 . . . 483	436/484 (90%)	0.0
	(Rat), 501 aa.	1 . . . 484	460/484 (94%)

[0438] PFam analysis predicts that the NOV22a protein contains the domains shown in the Table 22E.

TABLE 22E
Domain Analysis of NOV22a
		Identities/
		Similarities
Pfam Domain	NOV22a Match Region	for the Matched Region	Expect Value
PHD	62 . . . 108	11/53 (21%)	0.97
		28/53 (53%)
zf-MIZ	80 . . . 111	13/53 (25%)	0.4
		21/53 (40%)
RPH3A_effector	1 . . . 237	61/318 (19%)	0.035
		101/318 (32%)
C2	373 . . . 462	36/97 (37%)	8.6e−25
		71/97 (73%)
C2	528 . . . 617	37/97 (38%)	2.6e−24
		71/97 (73%)

Example 23

[0439] 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: 57	5993 bp
NOV23a.	GAGCGCGCCGTCCTCGAGTCCCCGAGCCGCGGAGCCCGCCCGCGCCCCTCGGGCCGCC
CG133903-01
DNA Sequence	CCGCGTCCCTCGCCATGGCGCGGCTCGCGGACTACTTCGTGCTGGTGGCGTTCGGGCC
	GCACCCGCGCGGGAGTGGGGAAGGCCAGGGCCAGATTCTGCAGCGCTTCCCAGAGAAG
	GACTGGGAGGACAACCCATTCCCCCAGGGCATCGAGCTGTTTTGCCAGCCCAGCGGGT
	GGCAGCTGTGTCCCGAGAGGAATCCACCGACCTTCTTTGTTGCTGTCCTCACCGACAT
	CAACTCCGAGCGCCACTACTGCGCCTGCTTGACCTTCTGGGAGCCAGCGGAGCCTTCA
	CAGGAAACGACGCGCGTGGAGGATGCCACAGAGAGGGAGGAAGAGGGGGATGAGGGAG
	GCCAGACCCACCTGTCTCCCACAGCACCTGCCCCATCTGCCCAGCTGTTTGCACCGAA
	GACGCTGGTACTGGTGTCGCGACTCGACCACACGGAGGTGTTCAGGAACAGCCTTGGC
	CTCATCTATGCCATCCACGTGGAGGGCCTGAATGTGTGCCTGGAGAACGTGATTGGGA
	ACCTGCTGACGTGCACTGTGCCCCTGGCTGGGGGCTCGCAGAGGACGATCTCTTTGGG
	GGCTGGTGACCGGCAGGTCATCCAGACTCCACTGGCCGACTCGCTGCCCGTCAGCCGC
	TGCAGCGTGGCCCTGCTCTTCCGCCAGCTAGGCATCACCAACGTGCTGTCTTTGTTCT
	GTGCCGCCCTCACGGAGCACAAGGTTCTCTTCCTGTCCCGGAGCTACCAGCGGCTCGC
	CGATGCCTGTAGGGGCCTCCTGGCACTGCTGTTTCCTCTCAGATACAGCTTCACCTAT
	GTGCCCATCCTGCCGGCTCAGCTGCTGGAGGTCCTCAGCACACCCACGCCCTTCATCA
	TTGGGGTCAACGCGGCCTTCCAGGCAGAGACCCAGGAGCTGCTCGATGTGATTGTTGC
	TGATCTGGATGGAGGGACGGTCACCATTCCTGAGTGTGTGCACATTCCACCCTTGCCA
	GAGCCACTGCAGAGTCAGACGCACAGTGTGCTGAGCATGGTCCTGGACCCGGAGCTGG
	AGTTGGCTGACCTCGCCTTCCCTCCGCCCACGACATCCACCTCCTCCCTGAAGATGCA
	GGACAAGGAGCTGCGCGCGGTCTTCCTGCGGCTGTTCGCTCAGCTGCTGCAGGGCTAT
	CGCTGGTGCCTGCACGTCGTGCGCATCCACCCGGAGCCTGTCATCCGCTTCCATAAGG
	CAGCCTTCCTGGGGCAGCGTGGGCTGGTAGAGGACGATTTCCTGATGAAGGTGCTGGA
	GGGCATGGCCTTTGCTGGCTTTGTGTCAGAGCGTGGGGTCCCATACCGCCCTACGGAC
	CTGTTCGATGAGCTGGTGGCCCACGAGGTGGCAAGGATGCGGGCGGATGAGAACCACC
	CCCAGCGTGTCCTGCGTCACGTCCAGGAACTGGCAGAGCAGCTCTACAAGAACGAGAA
	CCCGTACCCAGCCGTGGCGATGCACAAGGTACAGAGGCCCGGTGAGAGCAGCCACCTG
	CGACGGGTGCCCCGACCCTTCCCCCGGCTGGATGAGGGCACCGTGCAGTGGATCGTGG
	ACCAGGCTGCAGCCAAGATGCAGGGTGCACCCCCAGCTGTGAAGGCCGAGAGGAGGAC
	CACCGTGCCCTCAGGGCCCCCCATGACTGCCATACTGGAGCGGTGCAGTGGGCTGCAT
	GTCAACAGCGCCCGGCGGCTGGAGGTTGTGCGCAACTGCATCTCCTACGTGTTTGAGG
	GGAAAATGCTTGAGGCCAAGAAGCTGCTCCCAGCCGTGTTGAGGGCCCTGAAGGGGCG
	AGTTGCCCGCCGCTGCCTCGCCCAGGAGCTGCACCTGCATGTGCAGCAGAACCGTGCG
	GTCCTGGACCACCAGCAGTTTGACTTTGTCGTCCGTATGATGAACTGCTGCCTGCAGG
	ACTGCACTTCTCTGGACGAGCATGGCATTGCGGCGGCTCTGCTGCCTCTGGTCACAGC
	CTTCTGCCGGAAGCTGAGCCCGGGGGTGACGCAGTTTGCATACAGCTGTGTGCAGGAG
	CACGTGGTGTGGAGCACGCCACAGTTCTGGGAGGCCATGTTCTATGGGGATGTGCAGA
	CTCACATCCGGGCCCTCTACCTGGAGCCCACGGAGGACCTGGCCCCCGCCCAGGAGGT
	TGGGGAGGCACCTTCCCAGGAGGACGAGCGCTCTGCCCTAGACGTGGCTTCTGAGCAG
	CGGCGCTTGTGGCCAACTCTGAGTCGTGAGAAGCAGCAGGAGCTGGTGCAGAAGGAGG
	AGAGCACGGTGTTCAGCCAGGCCATCCACTATGCCAACCGCATGAGCTACCTCCTCCT
	GCCCCTGGACAGCAGCAAGAGCCGCCTACTTCGGGAGCGTGCCGGGCTGGGCGACCTG
	GAGAGCGCCAGCAACAGCCTGGTCACCAACAGCATGGCTGGCAGTGTGGCCGAGAGCT
	ATGACACGGAGAGCGGCTTCGAGGATGCAGAGACCTGCGACGTAGCTGGGGCTGTGGT
	CCGCTTCATCAACCGCTTTGTGGACAAGGTCTGCACGGAGAGTGGGGTCACCAGCGAC
	CACCTCAAGGGGCTGCATGTCATGGTGCCAGACATTGTCCAGATGCACATCGAGACCC
	TGGAGGCCGTGCAGCGGGAGAGCCGGAGGCTGCCGCCCATCCAGAAGCCCAAGCTGCT
	GCGGCCGCGCCTGCTGCCGGGTGAGGAGTGTGTGCTGGACGGCCTGCGCGTCTACCTG
	CTGCCGGATGGGCGTGAGGAGGGCGCGGGGGGCAGTGCTGGGGGACCAGCATTGCTCC
	CAGCTGAGGGCGCCGTCTTCCTCACCACGTACCGGGTCATCTTCACGGGGATGCCCAC
	GGACCCCCTGGTTGGGGAGCAGGTGGTGGTCCGCTCCTTCCCGGTGGCTGCGCTGACC
	AAGGAGAAGCGCATCAGCGTCCAGACCCCTGTGGACCAGCTCCTGCAGGACGGGCTCC
	AGCTGCGCTCCTGCACATTCCAGCTGCTGAAAATGGCCTTTGACGAGGAGGTGGGGTC
	TGACAGCGCCGAGCTCTTCCGTAAGCAGCTGCATAAGCTGCGGTACCCGCCGGACATC
	AGGGCCACCTTTGCGTTCACCTTGGGCTCTGCCCACACACCTCGCCGGCCACCGCGAG
	TCACCAAGGACAAGGGTCCTTCCCTCAGAACCCTGTCCCGGAACCTGGTCAAGAACGC
	CAAGAAGACCATCGGGCGGCAGCATGTCACTCGCAAGAAGTACAACCCCCCCAGCTGG
	GAGCACCGGGGCCAGCCGCCCCCTGAGGACCAGGAGGACGAGATCTCAGTGTCGGAGG
	AGCTGGAGCCCAGCACGCTGACCCCGTCCTCAGCCCTGAAGCCCTCCGACCGCATGAC
	CATGAGCAGCCTGGTGGAAAGGGCTTGCTGTCGCGACTACCAGCGCCTCGGTCTGGGC
	ACCCTGAGCAGCAGCCTGAGCCGGGCCAAGTCTGAGCCCTTCCGCATTTCTCCGGTCA
	ACCGCATGTATGCCATCTGCCGCAGCTACCCAGGGCTGCTGATCGTGCGCCAGAGTGT
	CCAGGACAACGCCCTGCAGCGCGTGTCCCGCTGCTACCGCCAGAACCGCTTCCCCGTG
	GTCTGCTGGCGCAGCGGGCGGTCCAAGGCGGTGCTGCTGCGCTCTGGAGGCCTGCATG
	GCAAAGGTGTCGTCGGCCTCTTCAAGGCCCAGAACGCACCTTCTCCAGGCCAGTCCCA
	GGCGGACTCGAGTAGCCTGGAGCAGGAGAAGTACCTGCAGGCTGTGGTCAGCTCCATG
	CCCCGCTACGCCGACGCGTCGGGACGCAACACGCTTAGCGGCTTCTCCTCAGCCCACA
	TGGGCAGTCACGGTAAGTGGGGCAGTGTCCGGACCAGTGGACGCAGCAGTGGCCTTGG
	CACCGATGTGGGCTCCCGGCTAGCTGGCAGAGACGCGCTGGCCCCACCCCAGGCCAAC
	GGGGGCCCTCCCGACCCGGGCTTCCTGCGTCCGCAGCGAGCAGCCCTCTATATCCTTG
	GGGACAAAGCCCAGCTCAAGGGTGTGCGGTCAGACCCCCTGCAGCAGTGGGAGCTGGT
	GCCCATTGAGGTATTCGAGGCACGGCAGGTGAAGGCTAGCTTCAAGAAGCTGCTGAAA
	GCATGTGTCCCAGGCTGCCCCGCTGCTGAGCCCAGCCCAGCCTCCTTCCTGCGCTCAC
	TGGAGGACTCAGAGTGGCTGATCCAGATCCACAAGCTGCTGCAGGTGTCTGTGCTGGT
	GGTGGAGCTCCTGGATTCAGGCTCCTCCGTGCTGGTGGGCCTGGAGGATGGCTGGGAC
	ATCACCACCCAGGTGGTATCCTTGGTGCAGCTGCTCTCAGACCCCTTCTACCGCACGC
	TGGAGGGCTTTCGCCTGCTGGTGGAGAAGGAGTGGCTGTCCTTCGGCCATCGCTTCAG
	CCACCGTGGAGCTCACACCCTGGCCGGGCAGAGCAGCGGCTTCACACCCGTCTTCCTG
	CAGTTCCTGGACTGCGTACACCAGGTCCACCTGCAGTTCCCCATGGAGTTTGAGTTCA
	GCCAGTTCTACCTCAAGTTCCTCGGCTACCACCATGTGTCCCGCCGTTTCCGGACCTT
	CCTGCTCGACTCTGACTATGAGCGCATTGAGCTGGGGCTGCTGTATGAGGAGAAGGGG
	GAACGCAGGGGCCAGGTGCCGTGCAGGTCTGTGTGGGAGTATGTGGACCGGCTGAGCA
	AGAGGACGCCTGTGTTCCACAATTACATGTATGCGCCCGAGGACGCAGAGGTCCTGCG
	GCCCTACAGCAACGTGTCCAACCTGAAGGTGTGGGACTTCTACACTGAGGAGACGCTG
	GCCGAGGCCCTCCCTATGACTGGGAACTGGCCCAGGGGCCCCCTGAACCCCCAGAGGA
	AGAACGGTCTGATGGAGGCGTCCCCAGAGCAGCGCCGCGTGGTGTGGCCCTGTTACGA
	CAGCTGCCCGCGGGCCCAGCCTGACGCCATCTCACGCCTGCTGGAGGAGCTGCAGAGG
	CTGGAGACAGAGTTGGGCCAACCCGCTGAGCGCTGGAAGGACACCTGGGACCGGGTGA
	AGGCTGCACAGCGCCTCGAGGGCCGGCCAGACGGCCGTGGCACCCCTAGCTCCCTCCT
	TGTGTCCACCGCACCCCACCACCGTCGCTCGCTGGGTGTGTACCTGCAGGAGGGGCCC
	GTGGGCTCCACCCTGAGCCTCAGCCTGGACAGCGACCAGAGTAGTGGCTCAACCACAT
	CCGGCTCCCGTCAGGCTGCCCGCCGCAGCACCAGCACCCTGTACAGCCAGTTCCAGAC
	AGCAGAGAGTGAGAACAGGTCCTACGAGGGCACTCTGTACAAGAAGGGGGCCTTCATG
	AAGCCTTGGAAGGCCCGCTGGTTCGTGCTGGACAAGACCAAGCACCAGCTGCGCTACT
	ACGACCACCGTGTGGACACAGAGTGCAAGGGTGTCATCGACTTGGCGGAGGTGGAGGC
	TGTGGCACCTGGCACGCCCACTATGGGTGCCCCTAAGACTGTGGACGAGAAGGCCTTC
	TTTGACGTGAAGACAACGCGTCGCGTTTACAACTTCTGTGCCCAGGACGTGCCCTCGG
	CCCAGCAGTGGGTGGACCGGATCCAGAGCTGCTGTCGGACGCCTGAGCCTCCCAGCCC
	TGCCCGGCTGCTCTGCTCTCGTTACCGACCACTAGGGGTGGCAGGGCCGCCCCGGCCA
	TGTTTACAGCCCCGGCCCTCGACAGTACTGAGCCCCGAGCCCCCAGCACTTGTGTGTA
	CAGCCCCCGTCCCCGCCCCGCCCCGCCCGGCCGGCCCTAACTTATTTTGGCGTCACAG
	CTGAGCACCGTGCCGGGAGGTGGCCAAGGTACAGCCCGCAATGGGCCTGTAAATAGTC
	CGGCCCCGTCAGCGTGTGCTGGTCCACGGGCTCAGGCGAGTTTCTAGAAAGAGTCTAT
	ATAAAGAGAGAACTAACGC
	ORF Start: ATG at 73	ORF Stop: TGA at 5860
	SEQ ID NO: 58	1929 aa	MW at 215121.1 kD
NOV23a.	MARLADYFVLVAFGPHPRGSGEGQGQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCP
CG133903-01
Protein Sequence	ERNPPTFFVAVLTDINSERHYCACLTFWEPAEPSQETTRVEDATEREEEGDEGGQTHL
	SPTAPAPSAQLFAPKTLVLVSRLDHTEVFRNSLGLIYAIHVEGLNVCLENVIGNLLTC
	TVPLAGGSQRTISLGAGDRQVIQTPLADSLPVSRCSVALLFRQLGITNVLSLFCAALT
	EHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEVLSTPTPFIIGVNA
	AFQAETQELLDVIVADLDGGTVTIPECVHIPPLPEPLQSQTHSVLSMVLDPELELADL
	AFPPPTTSTSSLKMQDKELRAVFLRLFAQLLQGYRWCLHVVRIHPEPVIRFHKAAFLG
	QRGLVEDDFLMKVLEGMAFAGFVSERGVPYRPTDLFDELVAHEVARMRADENHPQRVL
	RHVQELAEQLYKNENPYPAVAMHKVQRPGESSHLRRVPRPFPRLDEGTVQWIVDQAAA
	KMQGAPPAVKAERRTTVPSGPPMTAILERCSGLHVNSARRLEVVRNCISYVFEGKMLE
	AKKLLPAVLRALKGRVARRCLAQELHLHVQQNRAVLDHQQFDFVVRMMNCCLQDCTSL
	DEHGIAAALLPLVTAFCRKLSPGVTQFAYSCVQEHVVWSTPQFWEAMFYGDVQTHIRA
	LYLEPTEDLAPAQEVGEAPSQEDERSALDVASEQRRLWPTLSREKQQELVQKEESTVF
	SQAIHYANRMSYLLLPLDSSKSRLLRERAGLGDLESASNSLVTNSMAGSVAESYDTES
	GFEDAETCDVAGAVVRFINRFVDKVCTESGVTSDHLKGLHVMVPDIVQMHIETLEAVQ
	RESRRLPPIQKPKLLRPRLLPGEECVLDGLRVYLLPDGREEGAGGSAGGPALLPAEGA
	VFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTPVDQLLQDGLQLRSC
	TFQLLKMAFDEEVGSDSAELFRKQLHKLRYPPDIRATFAFTLGSAHTPGRPPRVTKDK
	GPSLRTLSRNLVKNAKKTIGRQHVTRKKYNPPSWEHRGQPPPEDQEDEISVSEELEPS
	TLTPSSALKPSDRMTMSSLVERACCRDYQRLGLGTLSSSLSRAKSEPFRISPVNRMYA
	ICRSYPGLLIVRQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVV
	GLFKAQNAPSPGQSQADSSSLEQEKYLQAVVSSMPRYADASGRNTLSGFSSAHMGSHG
	KWGSVRTSGRSSGLGTDVGSRLAGRDALAPPQANGGPPDPGFLRPQRAALYILGDKAQ
	LKGVRSDPLQQWELVPIEVFEARQVKASFKKLLKACVPGCPAAEPSPASFLRSLEDSE
	WLIQIHKLLQVSVLVVELLDSGSSVLVGLEDGWDITTQVVSLVQLLSDPFYRTLEGFR
	LLVEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQFPMEFEFSQFYL
	KFLGYHHVSRRFRTFLLDSDYERIELGLLYEEKGERRGQVPCRSVWEYVDRLSKRTPV
	FHNYMYAPEDAEVLRPYSNVSNLKVWDFYTEETLAEALPMTGNWPRGPLNPQRKNGLM
	EASPEQRRVVWPCYDSCPRAQPDAISRLLEELQRLETELGQPAERWKDTWDRVKAAQR
	LEGRPDGRGTPSSLLVSTAPHHRRSLGVYLQEGPVGSTLSLSLDSDQSSGSTTSGSRQ
	AARRSTSTLYSQFQTAESENRSYEGTLYKKGAFMKPWKARWFVLDKTKHQLRYYDHRV
	DTECKGVIDLAEVEAVAPGTPTMGAPKTVDEKAFFDVKTTRRVYNFCAQDVPSAQQWV
	DRIQSCCRTPEPPSPARLLCSRYRPLGVAGPPRPCLQPRPSTVLSPEPPALVCTAPVP
	APPRPAGPNLFWRHS

[0440] Further analysis of the NOV23a protein yielded the following properties shown in Table 23B.

TABLE 23B
Protein Sequence Properties NOV23a
PSort     0.5500 probability located in endoplasmic reticulum
analysis: (membrane); 0.2477 probability located in lysosome
          (lumen); 0.1125 probability located in microbody
          (peroxisome); 0.1000 probability located in endoplasmic
          reticulum (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0441] A search of the NOV23a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 23C.

TABLE 23C
Geneseq Results for NOV23a
		NOV23a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organisim/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB62814	Drosophila melanogaster	1..1713	740/1813 (40%)	0.0
	polypeptide SEQ ID NO 15234—	1..1777	1038/1813 (56%)
	Drosophila melanogaster, 1993
	aa. [WO200171042-A2, 27-SEP-
	2001]
AAY96965	Human nuclear dual-specificity	969..1862	471/908 (51%)	0.0
	phosphatase—Homo sapiens, 893	1..888	611/908 (66%)
	aa. [WO200039277-A2, 06-JUL-
	2000]
ABG19079	Novel human diagnostic protein	726..1345	477/623 (76%)	0.0
	#19070—Homo sapiens, 1232 aa.	347..918	507/623 (80%)
	[WO200175067-A2, 11-OCT-
	2001]
ABG19079	Novel human diagnostic protein	726..1345	477/623 (76%)	0.0
	#19070—Homo sapiens, 1232 aa.	347..918	507/623 (80%)
	[WO200175067-A2, 11-OCT-
	2001]
AAM25656	Human protein sequence SEQ ID	1397..1862	255/471 (54%)	e−142
	NO:1171—Homo sapiens, 464 aa.	1..460	322/471 (68%)
	[WO200153455-A2, 26-JUL-
	2001]

[0442] In a BLAST search of public sequence datbases, the NOV23a protein was found to have homology to the proteins shown in the BLASTP data in Table 23D.

TABLE 23D
Public BLASTP Results for NOV23a
			Identities/
Protein		NOV23a	Similarities for
Accession		Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
O60228	Nuclear dual-specificity	237 . . . 1929	1692/1693 (99%)	0.0
	phosphatase - Homo sapiens	5 . . . 1697	1693/1693 (99%)
	(Human), 1697 aa (fragment).
Q9UGB8	DJ579N16.2 (SET binding factor	237 . . . 1862	1601/1627 (98%)	0.0
	1) - Homo sapiens (Human),	1 . . . 1627	1606/1627 (98%)
	1631 aa (fragment).
Q96GR9	Similar to SET binding factor 1 -	938 . . . 1862	901/926 (97%)	0.0
	Homo sapiens (Human), 930 aa	1 . . . 926	906/926 (97%)
	(fragment).
Q9C097	KIAA1766 protein - Homo	30 . . . 1163	713/1141 (62%)	0.0
	sapiens (Human), 1123 aa	1 . . . 1122	882/1141 (76%)
	(fragment).
Q9VGH9	SBF protein - Drosophila	1 . . . 1713	740/1813 (40%)	0.0
	melanogaster (Fruit fly), 1993 aa.	1 . . . 1777	1038/1813 (56%)

[0443] PFam analysis predicts that the NOV23a protein contains the domains shown in the Table 23E.

TABLE 23E
Domain Analysis of NOV23a
		Identities/
		Similarities
	NOV23a	for the	Expect
Pfam Domain	Match Region	Matched Region	Value
DENN	171 . . . 310	53/154 (34%)	2.4e−29
		92/154 (60%)
GRAM	882 . . . 968	19/97 (20%)	9.1e−17
		68/97 (70%)
PH	1761 . . . 1864	30/104 (29%)	1.8e−16
		76/104 (73%)

Example 24

[0444] 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: 59	268O bp
NOV24a.	TCCGACGCCGTCGCTGGGACCAAGATGGACCTCCCGGCGCTGCTCCCCGCCCCGACTG
CG133995-01
DNA Sequence	CGCGCGGAGGGCAACATGGCGGCGGCCCCGGCCCGCTCCGCCGAGCCCCAGCGCCGCT
	CGGCGCGAGCCCCGCGCGCCGCCGCCTGCTACTGGTGCGGGGCCCTGAAGATGGCGGG
	CCCGGGGCGCGGCCCGGGGAGGCCTCCGGGCCAAGCCCGCCGCCCGCCGAGGACGACA
	GCGACGGCGACTCTTTCTTGGTGCTGCTGGAAGTGCCGCACGGCGGCGCTGCCGCCGA
	GGCTGCCGGATCACAGGAGGCCGAGCCTGGCTCCCGTGTCAACCTGGCGAGCCGCCCC
	GAGCAGGGCCCCAGCGGCCCGGCCGCCCCCCCCGGCCCTGGCGTAGCCCCGGCGGGCG
	CCGTCACCATCAGCAGCCAGGACCTGCTGGTGCGTCTCGACCGCGGCGTCCTCGCGCT
	GTCTGCGCCGCCCGGCCCCGCAACCGCGGGCGCCGCCGCTCCCCGCCGCGCGCCCCAG
	GGCCTCGGCCCCAGCACGCCCGGCTACCGCTGCCCCGAGCCGCAGTGCGCGCTGGCCT
	TCGCCAAGAAGCACCAGCTCAAGGTGCACCTGCTCACGCACGGCGGCGGTCAGGGCCG
	GCGGCCCTTCAAGTGCCCACTGGAGGGCTGTGGTTGGGCCTTCACAACGTCCTACAAG
	CTCAAGCGGCACCTGCAGTCGCACGACAAGCTGCGGCCCTTCGGCTGTCCAGTGGGCG
	GCTGTGGCAAGAAGTTCACTACGGTCTATAACCTCAAGGCGCACATGAAGGGCCACGA
	GCAGGAGAGCCTGTTCAAGTGCGAGGTGTGCGCCGAGCGCTTCCCCACGCACGCCAAG
	CTCAGCTCCCACCAGCGCAGCCACTTCGAGCCCGAGCGCCCTTACAAGTGTGACTTTC
	CCGGTTGTGAGAAGACATTTATCACAGTGAGTGCCCTGTTTTCCCATAACCGAGCCCA
	CTTCAGGGAACAAGAGCTCTTTTCCTGCTCCTTTCCTGGGTGCACGAGGAAGCAGTAT
	GATAAAGCCTGTCGGCTGAAAATTCACCTGCGGAGCCATACAGGTGAAAGACCATTTA
	TTTGTGACTCTGACAGCTGTGGCTGGACCTTCACCAGCATGTCCAAACTTCTAAGGCA
	CAGAAGGAAACATGACGATGACCGGAGGTTTACCTGCCCTGTCGAGGGCTGTGGGAAA
	TCATTCACCAGAGCAGAGCATCTGAAAGGCCACAGCATAACCCACCTAGGCACAAAGC
	CGTTCGAGTGTCCTGTGGAAGGATGTTGCGCGAGGTTCTCCGCTCGTAGCAGTCTGTA
	CATTCACTCTAAGAAACACGTGCAGGATGTGGGTGCTCCGAAAAGCCGTTGCCCAGTT
	TCTACCTGCAACAGACTCTTCACCTCCAAGCACAGCATGAAGGCGCACATGGTCAGAC
	AGCACAGCCGGCGCCAAGATCTCTTACCTCAGCTAGAAGCTCCGAGTTCTCTTACTCC
	CAGCAGTGAACTCAGCAGCCCAGGCCAAAGTGAGCTCACTAACATGGATCTTGCTGCA
	CTCTTCTCTGACACACCTGCCAATGCTAGTGGTTCTGCAGGTGGGTCGGATGAGGCTC
	TGAACTCCGGAATCCTGACTATTGACGTCACTTCTGTGAGCTCCTCTCTGGGAGGGAA
	CCTCCCTGCTAATAATAGCTCCCTAGGGCCGATGGAACCCCTGGTCCTGGTGGCCCAC
	AGTGATATTCCCCCAAGCCTGGACAGCCCTCTGGTTCTCGGGACAGCAGCCACGGTTC
	TGCAGCAGGGCAGCTTCAGTGTGGATGACGTGCAGACTGTGAGTGCAGGAGCATTAGG
	CTGTCTGGTGGCTCTGCCCATGAAGAACTTGAGTGACGACCCACTGGCTTTGACCTCC
	AATAGTAACTTAGCAGCACATATCACCACACCGACCTCTTCGAGCACCCCCCGAGAAA
	ATGCCAGTGTCCCGGAACTGCTGGCTCCAATCAAGGTGGAGCCGGACTCGCCTTCTCG
	CCCAGGAGCAGTTGGGCAGCAGGAAGGAAGCCATGGGCTGCCCCAGTCCACGTTGCCC
	AGTCCAGCAGAGCAGCACGGTGCCCAGGACACAGAGCTCAGTGCAGGCACTGGCAACT
	TCTATTTGGAAAGTGGGGGCTCAGCAAGAACTGATTACCGAGCCATTCAACTAGCCAA
	GGAAAAAAAGCAGAGAGGAGCGGGGAGCAATGCAGGAGCCTCACAGTCTACTCAGAGA
	AAAATAAAAGAAGGCAAAATGAGTCCTCCCCATTTCCATGCAAGCCAGAACAGTTGGT
	TGTGTGGGAGCCTCGTGGTGCCCAGCGGAGGACGGCCAGGACCAGCTCCAGCAGCTGG
	GGTGCAGTGCGGGGCGCAGGGCGTCCAGGTCCAGCTGGTGCAGGATGACCCCTCCGGC
	GAAGGTGTCCTGCCCTCGGCCCGCGGCCCAGCCACCTTCCTCCCCTTCCTCACTGTGG
	ACCTGCCCGTCTACGTCCTCCAGGAGGTGCTCCCCTCATCTGGAGGCCCTGCTGGACC
	GGAGGCCACCCAGTTCCCAGGAAGCACTATCAACCTGCAGGATCTGCAGTGACGGCAG
	CCTCGGCCTGGGCAGGCCCAAGGCCACGGTCTAGGACACACCTTCCCTGAGACTCATG
	ACATGAGCCTGG
	ORF Start: ATG at 25	ORF Stop: TGA at 2602
	SEQ ID NO: 60	859 aa	MW at 90169.5 kD
NOV24a.	MDLPALLPAPTARGGQHGGGPGPLRRAPAPLGASPARRRLLLVRGPEDGGPGARPGEA
CG133995-01
Protein Sequence	SGPSPPPAEDDSDGDSFLVLLEVPHGGAAAEAAGSQEAEPGSRVNLASRPEQGPSGPA
	APPGPGVAPAGAVTISSQDLLVRLDRGVLALSAPPGPATAGAAAPRRAPQGLGPSTPG
	YRCPEPQCALAFAKKHQLKVHLLTHGGGQGRRPFKCPLEGCGWAFTTSYKLKRHLQSH
	DKLRPFGCPVGGCGKKFTTVYNLKAHMKGHEQESLFKCEVCAERFPTHAKLSSHQRSH
	FEPERPYKCDFPGCEKTFITVSALFSHNRAHFREQELFSCSFPGCTRKQYDKACRLKI
	HLRSHTGERPFICDSDSCGWTFTSMSKLLRHRRKHDDDRRFTCPVEGCGKSFTRAEHL
	KGHSITHLGTKPFECPVEGCCARFSARSSLYIHSKKHVQDVGAPKSRCPVSTCNRLFT
	SKHSMKAHMVRQHSRRQDLLPQLEAPSSLTPSSELSSPGQSELTNMDLAALFSDTPAN
	ASGSAGGSDEALNSGILTIDVTSVSSSLGGNLPANNSSLGPMEPLVLVAHSDIPPSLD
	SPLVLGTAATVLQQGSFSVDDVQTVSAGALGCLVALPMKNLSDDPLALTSNSNLAAHI
	TTPTSSSTPRENASVPELLAPIKVEPDSPSRPGAVGQQEGSHGLPQSTLPSPAEQHGA
	QDTELSAGTGNFYLESGGSARTDYRAIQLAKEKKQRGAGSNAGASQSTQRKIKEGKMS
	PPHFHASQNSWLCGSLVVPSGGRPGPAPAAGVQCGAQGVQVQLVQDDPSGEGVLPSAR
	GPATFLPFLTVDLPVYVLQEVLPSSGGPAGPEATQFPGSTINLQDLQ

[0445] Further analysis of the NOV24a protein yielded the following properties shown in Table 24B.

TABLE 24B
Protein Sequence Properties NOV24a
PSort     0.9600 probability located in nucleus; 0.3000 probability
analysis: located in microbody (peroxisome); 0.1000 probability
          located in mitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0446] A search of the NOV24a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 24C.

TABLE 24C
Geneseq Results for NOV24a
		NOV24a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organisim/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM79014	Human protein SEQ ID NO 1676—	1..710	470/816 (57%)	0.0
	Homo sapiens, 803 aa.	1..802	527/816 (63%)
	[WO200157190-A2, 09-AUG-
	2001]
AAM79998	Human protein SEQ ID NO 3644—	1..710	460/811 (56%)	0.0
	Homo sapiens, 904 aa.	102..903	518/811 (63%)
	[WO200157190-A2, 09-AUG-
	2001]
AAB94782	Human protein sequence SEQ ID	469..859	391/391 (100%)	0.0
	NO:15884—Homo sapiens, 391 aa.	1..391	391/391 (100%)
	[EP1074617-A2, 07-FEB-2001]
AAB41289	Human ORFX ORF1053	482..710	229/229 (100%)	e−125
	polypeptide sequence SEQ ID	11..239	229/229 (100%)
	NO:2106—Homo sapiens, 240 aa.
	[WO200058473-A2, 05-OCT-
	2000]
AAU27665	Human protein AFP162878—	753..859	107/107 (100%)	6e−58
	Homo sapiens, 107 aa.	1..107	107/107 (100%)
	[WO200166748-A2, 13-SEP-2001]

[0447] In a BLAST search of public sequence datbases, the NOV24a protein was found to have homology to the proteins shown in the BLASTP data in Table 24D.

TABLE 24D
Public BLASTP Results for NOV24a
		NOV24a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q99J65	Hypothetical 80.6 kDa protein - Mus	1 . . . 697	548/711 (77%)	0.0
	musculus (Mouse), 754 aa.	1 . . . 697	586/711 (82%)
P98169	Zinc finger X-linked protein ZXDB -	1 . . . 710	470/816 (57%)	0.0
	Homo sapiens (Human), 803 aa.	1 . . . 802	527/816 (63%)
P98168	Zinc finger X-linked protein ZXDA -	1 . . . 710	461/807 (57%)	0.0
	Homo sapiens (Human), 799 aa.	1 . . . 798	522/807 (64%)
Q9H891	CDNA FLJ13861 fis. clone	469 . . . 859	391/391 (100%)	0.0
	THYRO1001100, moderately similar	1 . . . 391	391/391 (100%)
	to zinc finger X-linked protein ZXDA
	(Unknown) (Protein for MGC:11349)
	(Hypothetical 39.9 kDa protein) -
	Homo sapiens (Human), 391 aa.
154340	DNA-binding protein - human, 457	211 . . . 661	334/454 (73%)	0.0
	aa (fragment).	1 . . . 450	371/454 (81%)

[0448] PFam analysis predicts that the NOV24a protein contains the domains shown in the Table 24E.

TABLE 24E
Domain Analysis of NOV24a
		Identities/
	NOV24a	Similarities for	Expect
Pfam Domain	Match Region	the Matched Region	Value
zf-C2H2	175 . . . 199	12/25 (48%)	0.0016
		18/25 (72%)
zf-C2H2	208 . . . 232	12/25 (48%)	1.2e−05
		22/25 (88%)
zf-C2H2	238 . . . 262	11/25 (44%)	1.9e−05
		22/25 (88%)
zf-C2H2	268 . . . 290	8/24 (33%)	0.00098
		19/24 (79%)
zf-C2H2	297 . . . 321	12/25 (48%)	0.00074
		18/25 (72%)
zf-C2H2	359 . . . 383	10/25 (40%)	0.0017
		18/25 (72%)
zf-C2H2	389 . . . 413	13/25 (52%)	1.1e−05
		21/25 (84%)
zf-C2H2	419 . . . 443	9/25 (36%)	0.37
		19/25 (76%)
zf-C2H2	452 . . . 477	8/26 (31%)	0.065
		22/26 (85%)

Example 25

[0449] 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: 61	379 bp
NOV25a.	TAATTAAATATGGGACAAGGTGTGCTGAAGAAGACTACTGGTCCTGTGAGATTGGCTG
CG134005-01
DNA Sequence	TATGTGAGAATCCACATGAGAGGCTAAGAATATTGTACACAAAGATCCTTGATGTTCT
	TGAGCAAATCCCTAAAAATGCAGCATATAAAAAGTGTACAGAACAGATTACAAATGAG
	AAGCTAGCTATGCTTAAAGTAGAACCAGATGTTAAAAAATTAGAAGACCAACTTCAAG
	ATGGCCAAATAGAAGAGGTGATTCATCAGGCTGAAAATGAACTAAATGTGGTGAGAAA
	AACGATGCAGTGGAAACCATGGGGGGCAATAGTGGAAGAGCCTCCTGCCAATCAGTGA
	AAACAGCCAATATAATTATTAAATGACTTTG
	ORF Start: ATG at 10	ORF Stop: TGA at 346
	SEQ ID NO: 62	112 aa	MW at 12827.8 kD
NOV25a.	MGQGVLKKTTGPVRLAVCENPHERLRILYTKILDVLEQIPKNAAYKKCTEQITNEKLA
CG134005-01
Protein Sequence	MLKVEPDVKKLEDQLQDGQIEEVIHQAENELNVVRKTMQWKPWGAIVEEPPANQ

[0450] Further analysis of the NOV25a protein yielded the following properties shown in Table 25B.

TABLE 25B
Protein Sequence Properties NOV25a
PSort     0.6500 probability located in cytoplasm: 0.1000 probability
analysis: located in mitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen): 0.0000 probability located in
          endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0451] 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/Organisim/Length[Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAG03840	Human secreted protein, SEQ ID	4..112	86/109 (78%)	9e−44
	NO: 7921—Homo sapiens, 116 aa.	3..111	95/109 (86%)
	[EP1033401-A2, 06-SEP-2000]
ABB62395	Drosophila melanogaster polypeptide	5..112	46/108 (42%)	5e−20
	SEQ ID NO 13977—Drosophila	4..111	68/108 (62%)
	melanogaster, 229 aa.
	[W0200171042-A2, 27-SEP-2001]
AAG24556	Arabidopsis thaliana protein	47..102	22/56 (39%)	6e−07
	fragment SEQ ID NO: 28275—	6..61	36/56 (64%)
	Arabidopsis thaliana, 120 aa.
	[EP1033405-A2, 06-SEP-2000]
AAG54944	Arabidopsis thaliana protein	47..102	21/56 (37%)	3e−06
	fragment SEQ ID NO: 70289—	6..61	35/56 (62%)
	Arabidopsis thaliana, 111 aa.
	[EP1033405-A2, 06-SEP-2000]
AAG24557	Arabidopsis thaliana protein	69..102	15/34 (44%)	0.002
	fragment SEQ ID NO: 28276—	2..35	25/34 (73%)
	Arabidopsis thaliana, 94 aa.
	[EP1033405-A2, 06-SEP-2000]

[0452] In a BLAST search of public sequence datbases, the NOV25a protein was found to have homology, to the proteins shown in the BLASTP data in Table 25D.

TABLE 25D
Public BLASTP Results forNOV25a
			Identities/
		NOV25a	Similarities
Protein		Residues/	for the
Accession		Match	Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
AAH20821	NADH dehydrogenase (ubiquinone) 1	4 . . . 112	86/109 (78%)	2e−43
	alpha subcomplex. 5 (13 kD. B13) -	3 . . . 111	95/109 (86%)
	Homo sapiens (Human). 116 aa.
Q16718	NADH-ubiquinone oxidoreductase 13	4 . . . 112	86/109 (78%)	2e−43
	kDa-B subunit (EC 1.6.5.3) (EC	2 . . . 110	95/109 (86%)
	1.6.99.3) (Complex 1-13Kd-B) (CI-
	13Kd-B) (Complex 1 subunit B13) -
	Homo sapiens (Human). 115 aa.
S28244	NADH dehydrogenase (ubiquinone)	4 . . . 112	84/109 (77%)	6e−43
	(EC 1.6.5.3) complex 1 13K-B chain -	3 . . . 111	96/109 (88%)
	bovine. 116 aa.
P23935	NADH-ubiquinone oxidoreductase 13	4 . . . 112	84/109 (77%)	6e−43
	kDa-B subunit (EC 1.6.5.3) (EC	2 . . . 110	96/109 (88%)
	1.6.99.3) (Complex 1-13Kd-B) (CI-
	13Kd-B) (Complex 1 subunit B13) -
	Bos taurus (Bovine). 115 aa.
Q9CY90	10, 11 days embryo cDNA. RIKEN	4 . . . 112	76/109 (69%)	6e−39
	full-length enriched library.	3 . . . 111	90/109 (81%)
	clone:2810016H15. full insert
	sequence - Mus musculus (Mouse).
	116 aa.

[0453] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25E.

TABLE 25E
Domain Analysis of NOV25a
	Pfam	NOV25a	Identities/	Expect
	Domain	Match	Similarities	Value
		Region	for the
			Matched Region

Example 26

[0454] 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: 63	789 bp
NOV26a.	AGTGATGCAATGTCATCTTAATGGAGCGACTGAAAACTGATGTGTGTAGAATGAAA
CG134014-01
DNA Sequence	GAACACATGGAAGATAGAGTAAATGTGGCAGATTTCAGAAAACTAGAATGGCTTTTCC
	CAGAAACAACAGCAAATTTTGATAAACTGTTAATTCAATATCGGGGATTTTGTGCTTA
	CACGTTTGCTGCAACAGATGGTCTTCTCCTTCCAGGTAATCCAGCAATTGGAATTTTA
	AAATATAAAGAAAAATATTACACATTCAATAGTAAAGATGCTGCATATTCATTTGCAG
	AAAATCCTGAACATTATATTGACATAGTTAGAGAAAAGGCCAAAAAAAATACAGAGTT
	AATTCAACTATTGGAACTTCATCAACAGTTTGAAACATTTATTCCATATTCTCAGATG
	AGAGATGCTGACAAACATTATATAAAACCAATTACAAAATGTGAAAGTAGCACACAGA
	CGAATACACACATACTGCCACCAACGATTGTGAGATCATATGAGTGGAATGAATGGGA
	ATTAAGAAGAAAAGCTATAAAATTGGCTAATTTGCGCCAGAAAGTTACTCACTCAGTA
	CAAACTGATCTTAGTCACTTGAGAAGAGAAAATTGTTCCCAAGTGTACCCTCCAAAGG
	ACACTAGCACCCAGTCCATGAGGGAAGACAGCACTGGGGTGCCCAGGCCTCAGATTTA
	CTTGGCTGGTCTTCGTGGAGGAAAGAGCGAAATCACCGATGAGGTCAAGGTGAACTTA
	ACTAGAGATGTGGATGAAACCTAATTACAGACAAC
	ORF Start: ATG at 5	ORF Stop: TAA at 776
	SEQ ID NO: 64	257 aa	MW at 29869.6 kD
NOV26a.	MQCHLNGATVKTDVCRMKEHMEDRVNVADFRKLEWLFPETTANFDKLLIQYRGFCAYT
CG134014-01
Protein Sequence	FAATDGLLLPGNPAIGILKYKEKYYTFNSKDAAYSFAENPEHYIDIVREKAKKNTELI
	QLLELHQQFETFIPYSQMRDADKHYIKPITKCESSTQTNTHILPPTIVRSYEWNEWEL
	RRKAIKLANLRQKVTHSVQTDLSHLRRENCSQVYPPKDTSTQSMREDSTGVPRPQIYL
	AGLRGGKSEITDEVKVNLTRDVDET

[0455] Further analysis of the NOV26a protein yielded the following properties shown in Table 26B.

TABLE 26B
Protein Sequence Properties NOV26a
PSort     0.4500 probability located in cytoplasm: 0.3000 probability
analysis: located in microbody (peroxisome): 0.1000 probability located
          in mitochondrial matrix space: 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0456] A search of the NOV26a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 26C.

TABLE 26C
Geneseq Results for NOV26a
		NOV26a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
ABB68169	Drosophila melanogaster polypeptide	39..208	50/176 (28%)	2e−08
	SEQ ID NO 31299—Drosophila	404..570	79/176 (44%)
	melanogaster, 576 aa.
	[WO200171042-A2, 27-SEP-2001]
AAB68357	Amino acid sequence of a maize	117..229	32/115 (27%)	7.1
	ZmMAD3 protein—Zea mays, 270	124..221	49/115 (41%)
	aa. [WO200131017-A2, 03-MAY-
	2001]
AAG91801	C glutamicum protein fragment SEQ	26..106	29/85 (34%)	7.1
	ID NO: 5555—Corynebacterium	137..213	40/85 (46%)
	glutamicum, 231 aa. [EP1108790-
	A2, 20-JUN-2001]
ABG09185	Novel human diagnostic protein	133..194	18/63 (28%)	9.3
	#9176—Homo sapiens, 348 aa.	130..192	31/63 (48%)
	[WO200175067-A2, 11-OCT-2001]
AAB84880	Bacillus subtillis CodY—Bacillus	16..145	34/136 (23%)	9.3
	subtilis, 257 aa. [WO200129183-A2,	60..193	62/136 (45%)
	26-APR-2001]

[0457] In a BLAST search of public sequence datbases, the NOV26a protein was found to have homology to the proteins shown in the BLASTP data in Table 26D.

TABLE 26D
Public BLASTP Results for NOV26a
		NOV26a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q95JU3	Hypothetical 71.1 kDa protein -	1 . . . 257	252/257 (98%)	e−147
	Macaca fascicularis (Crab eating	366 . . . 622	253/257 (98%)
	macaque) (Cynomolgus monkey).
	622 aa.
Q9DAP6	1700003M02Rik protein - Mus	5 . . . 257	199/253 (78%)	e−118
	musculus (Mouse). 257 aa.	5 . . . 257	229/253 (89%)
Q95K32	Hypothetical 51.7 kDa protein -	1 . . . 114	110/114 (96%)	4e−60
	Macaca fascicularis (Crab eating	338 . . . 451	111/114 (96%)
	macaque) (Cynomolgus monkey).
	452 aa.
Q95JX1	Hypothetical 45.5 kDa protein -	1 . . . 111	110/111 (99%)	5e−60
	Macaca fascicularis (Crab eating	284 . . . 394	110/111 (99%)
	macaque) (Cynomolgus monkey).
	397 aa.
Q8T4E2	AT02388p - Drosophila	39 . . . 208	50/176 (28%)	5e−08
	melanogaster (Fruit fly). 576 aa.	404 . . . 570	79/176 (44%)

[0458] PFam analysis predicts that the NOV26a protein contains the domains shown in the Table 26E.

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

Example 27

[0459] 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: 65	344 bp
NOV27a.	GTGATGATATGGCGACAACAAATTTTAATCTGCGACTTGAGCAAGATTTGCGTGATCG
CG134023-01
DNA Sequence	GGCATTTCCAGTGTTTGAGCGTTATGGACTGAGCGCATCACAAGCCTTTAAATTGTTT
	TTAACACAAGTTGCTGAGACCAATAAAATTCCCTTGTCTTTTGATTATGCAGAGACAG
	AGAATGTGCCGAATAGTGTCACAAGAAAAGCATTGACTGAAGCAAAAAATAGAACTGA
	TTTTTCAGATGCTTATGAAACACCTGAAGAATTTATGAAAGCGATGCAAGAATTAGCC
	AATGCGTAAGATATTAGCTGAAAGCCAATTTAAGAGAGATATTAAAAAGCAATT
	ORF Start: ATG at 9	ORF Stop: TAA at 297
	SEQ ID NO: 66	96 aa	MW at 11006.2 kD
NOV27a,	MATTNFNLRLEQDLRDRAFPVFERYGLSASQAFKLFLTQVAETNKIPLSFDYAETENV
CG134023-01
Protein Sequence	PNSVTRKALTEAKNRTDFSDAYETPEEFMKAMQELANA

[0460] Further analysis of the NOV27a protein yielded the following properties shown in Table 27B.

TABLE 27B
Protein Sequence Properties NOV27a
PSort     0.4500 probability located in cytoplasm; 0.4267 probability
analysis: located in mitochondrial matrix space: 0.1042 probability
          located in mitochondrial inner membrane: 0.1042 probability
          located in mitochondrial intermembrane space
SignalP   No Known Signal Sequence Predicted
analysis:

[0461] A search of the NOV27a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 27C.

TABLE 27C
Geneseq Results for NOV27a
		NOV27a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
	ABP25789 Streptococcus polypeptide SEQ ID	8..47	16/40 (40%)	0.12
		NO 754—Streptococcus agalactiae,	6..45	24/40 (60%)
		97 aa. [WO200234771-A2, 02-MAY-
		2002]
	ABP25790	Streptococcus polypeptide SEQ ID	3..54	16/52 (30%)	0.26
		NO 756—Streptococcus pyogenes,	13..64	25/52 (47%)
		104 aa. [WO200234771-A2, 02-
		MAY-2002]
	AAG84928	Shrimp white spot Bacilliform virus	32..95	22/68 (32%)	1.0
		(WSBV) protein 19—White spot	715..782	29/68 (42%)
		syndrome virus, 783 aa.
		[WO200138351-A2, 31-MAY-2001]
	AAY97010	S. cerevisiae essential gene YJL010C	29..93	15/65 (23%)	5.1
		product—Saccharomyces cerevisiae,	202..265	30/65 (46%)
		666 aa. [WO200039342-A2, 06-JUL-
		2000]
	AAW89421	Moraxella catarrhalis VH19	25..73	18/49 (36%)	6.7
		lactoferrin binding protein 2 (Lbp2)—	566..614	27/49 (54%)
		Moraxella catarrhalis, 905 aa.
		[WO9855606-A2, 10-DEC-1998]

[0462] In a BLAST search of public sequence datbases, the NOV27a protein was found to have homology to the proteins shown in the BLASTP data in Table 27D.

TABLE 27D
Public BLASTP Results for NOV27a
		NOV27a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9REP3	Negative regulator of translation -	1 . . . 92	65/92 (70%)	3e−28
	Zymomonas mobilis. 93 aa.	1 . . . 89	75/92 (80%)
Q9X443	Negative regulator of translation -	1 . . . 88	34/95 (35%)	3e−06
	Haemophilus influenzae. 98 aa.	1 . . . 91	50/95 (51%)
P71357	Hypothetical protein HI0710 -	1 . . . 88	34/95 (35%)	1e−05
	Haemophilus influenzae. 98 aa.	1 . . . 91	51/95 (52%)
Q8UGV0	Hypothetical protein Atu0935 -	9 . . . 71	20/63 (31%)	0.011
	Agrobacterium tumefaciens (strain	10 . . . 66	34/63 (53%)
	C58/ATCC 33970). 91 aa.
Q97SQ1	Hypothetical protein SP0275 -	1 . . . 91	22/91 (24%)	0.018
	Streptococcus pneumoniae. 87 aa.	1 . . . 86	47/91 (51%)

[0463] PFam analysis predicts that the NOV27a protein contains the domains shown in the Table 27E.

TABLE 27E
Domain Analysis of NOV27a
	Pfam	NOV27a	Identities/	Expect
	Domain	Match	Similarities	Value
		Region	for the Matched
			Region

Example 28

[0464] 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: 67	445 bp
NOV28a.	GATTAAATTTCCTCTATTGCTTGGTATGGTGCTGTTCTGGGAACAGACAAAATCACTT
CG134032-01
DNA Sequence	CACTGTCTTCAAGTACAACAGGACTTCAGCCAGAGCCGCACCATCCCCAGCCGCACCG
	TGGCCATCAGCGACGCTGCACAGTTACCTCATGACTACTGCACCACACAGGGGGGCAC
	TCTTCTCACCACACGGGGAGGAACTCAAATCTTTTATGATAGAAAGTTTCTGTTGGAT
	TATTGCAATTCTCCCATGGTTCAGACCCCACCCTGCCATCTACCAAATATCCCAGAAG
	TCACTAGCCCTGGCACCTTAATCGAAGACTCCAGAGTAGAAGTAAACAATTTGAACAA
	CATAAACAATCATGAGAGGAAACACGCAGTTGGGGATGATGCTCAGTTTGAGATGGGC
	ATCTGACTCTCCTGCAAGGATTAGAAGAAAAGCAGCAAT
	ORF Start: ATG at 26	ORF Stop: TGA at 410
	SEQ ID NO: 68	128 aa	MW at 14404.0 kD
NOV28a,	MVLFWEQTKSLHCLQVQQDFSQSRTIPSRTVAISDAAQLPHDYCTTQGGTLLTTRGGT
CG134032-01
Protein sequence	QIFYDRKFLLDYCNSPMVQTPPCHLPNIPEVTSPGTLIEDSRVEVNNLNNINNHERKH
	AVGDDAQFEMGI

[0465] Further analysis of the NOV28a protein yielded the following properties shown in Table 28B.

TABLE 28B
Protein Sequence Properties NOV28a
PSort     0.6500 probability located in cytoplasm; 0.2379 probability
analysis: located in lysosome (lumen): 0.1000 probability located in
          mitochondrial matrix space: 0.0000 probability located in
          endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0466] 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+HZ,49
AAY96148	Human elF-4E binding protein 4E-	21..128	93/109 (85%)	6e−49
	BP2—Homo sapiens, 120 aa.	12..120	98/109 (89%)
	[US6111077-A, 29-AUG-2000]
AAW94275	Human elF-4E-binding protein 4E-	21..128	93/109 (85%)	6e−49
	BP2—Homo sapiens, 120 aa.	12..120	98/109 (89%)
	[US5874231-A, 93-FEB-1999]
ABB57347	Mouse ischaemic condition related	23..128	54/108 (50%)	1e−19
	protein sequence SEQ ID NO:973—	12..117	72/108 (66%)
	Mus musculus, 117 aa.
	[WO200188188-A2, 22-NOV-2001]
ABB97146	Human tumour antigen related	23..128	55/109 (50%)	3e−19
	protein SEQ ID NO 48—Homo	12..118	72/109 (65%)
	sapiens, 118 aa. [WO200210369-A1,
	07-FEB-2002]
AAY96147	Human elF-4E binding protein 4E-	23..128	55/109 (50%)	3e−19
	BP1—Homo sapiens, 118 aa.	12..118	72/109 (65%)
	[US6111077-A, 29-AUG-2000]

[0467] In a BLAST search of public sequence datbases, the NOV28a protein was found to have homology to the proteins shown in the BLASTP data in Table 28D.

TABLE 28D
Public BLASTP Results for NOV28qa
		NOV28a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q13542	4E-binding protein 2 (Eukaryotic	21 . . . 128	93/109 (85%)	1e−48
	translation initiation factor 4E binding	12 . . . 120	98/109 (89%)
	protein 2) - Homo sapiens (Human).
	120 aa.
P70445	PHAS-II (Eukaryotic translation	21 . . . 128	90/109 (82%)	1e−46
	initiation factor 4E binding protein 2) -	12 . . . 120	96/109 (87%)
	Mus musculus (Mouse), 120 aa.
Q9CZ40	Eukaryotic translation initiation factor	23 . . . 128	55/108 (50%)	8e−20
	4E binding protein 1 - Mus musculus	12 . . . 117	72/108 (65%)
	(Mouse). 117 aa.
Q62622	PHAS-I - Rattus norvegicus (Rat).	23 . . . 128	54/108 (50%)	1e−19
	117 aa.	12 . . . 117	73/108 (67%)
Q60876	Eukaryotic translation initiation factor	23 . . . 128	54/108 (50%)	3e−19
	4E binding protein 1 (Insulin-	12 . . . 117	72/108 (66%)
	stimulated EIF-4E binding protein
	PHAS-I) - Mus musculus (Mouse).
	117 aa.

[0468] PFam analysis predicts that the NOV28a protein contains the domains shown in the Table 28E

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

Example 29

[0469] 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: 69	552 bp
NOV29a.	TCCAGGCAACGCTGCGGCTCCGCCCACGTCATGGCGCCCGAGGAGAACGCGGGGACAG
CG134304-01
DNA Sequence	AACTCTGGCTGCAGGGTTTCGAGCGCCGCTTCCTGGCGGCGCGCTCACTGCGCTCCTT
	CCCCTGGCAGAGCTTAGAGGCAAAGTTAAGAGACTCATCAGATTCTGAGCTGCTGCGG
	GATATTTTGCAGAAGACGAGGGCTGTCCACACGGAGCCTTTGGACGAGCTGTACGAGG
	TGCTGGCGGAGACTCTGATGGCCAAGGAGTCCACCCAGGGCCACCGGAGCTATTTGCT
	GACGTGCTGTATTGCCCAGAAGCCATCGTGTCACTGGTCGGGGTCCTGCGGAGGCTGG
	CTGCCTGCCGGGAGCACAAGCAGGCTCCTGAGGTCTACCTGGCCTTTACCGTCCGCAA
	CCCAGAGACGTGCCAGCTGTTCACCACCGAGCCAGGCTGGACTGGGATCAGATGGGAA
	GTGGAAGCTCATCATGACCAGAAACTGTTTCCCTACAGAGAGCACTTGGAGATGGCAA
	TGCTGAACCTCACACTGTAGGACTCACACA
	ORF Start: ATG at 31	ORF Stop: TGA at 526
	SEQ ID NO: 70	165 aa	MW at 18617.9 kD
NOV29a,	MAPEENAGTELWLQGFERRFLAARSLRSFPWQSLEAKLRDSSDSELLRDILQKTRAVH
CG134304-01
Protein Sequence	TEPLDELYEVLAETLMAKESTQGHRSYLLTCCIAQKPSCHWSGSCGGWLPAGSTSRLL
	RSTWPLPSATQRRASCSPPSQAGLGSDGKWKLIMTRNCFPTESTWRWQC

[0470] Further analysis of the NOV29a protein yielded the following properties shown in Table 29B.

TABLE 29B
Protein Sequence Properties NOV29a
PSort     0.6279 probability located in microbody (peroxisome); 0.1000
analysis: probability located in mitochondrial matrix space; 0.1000
          probability located in lysosome (lumen); 0.0000 probability
          located in endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0471] 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
Genesec1 Results for NOV29a
		NOV29a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB93042	Human protein sequence SEQ ID	1..164	150/164 (91%)	4e−85
	NO:11827—Homo sapiens, 165 aa.	1..164	154/164 (93%)
	[EP1074617-A2, 07-FEB-2001]
AAB36613	Human FLEXHT-35 protein	1..87	81/114 (71%)	6e−35
	sequence SEQ ID NO:35—Homo	1..114	82/114 (71%)
	sapiens, 330 aa. [WO200070047-
	A2, 23-NOV-2000]
ABG13115	Novel human diagnostic protein	1..87	79/114 (69%)	6e−34
	#13106—Homo sapiens, 425 aa.	23..136	81/114 (70%)
	[WO200175067-A2, 11-OCT-2001]
ABG13115	Novel human diagnostic protein	1..87	79/114 (69%)	6e−34
	#13106—Homo sapiens, 425 aa.	23..136	81/114 (70%)
	[WO200175067-A2, 11-OCT-2001]
ABG09575	Novel human diagnostic protein	19..97	60/79 (75%)	2e−22
	#9566—Homo sapiens, 379 aa.	89..158	62/79 (77%)
	[WO200175067-A2, 11-OCT-2001]

[0472] In a BLAST search of public sequence datbases, the NOV29a protein was found to have homology to the proteins shown in the BLASTP data in Table 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
Q9NVL1	CDNA FLJ10661 fis. clone	1 . . . 164	150/164 (91%)	1e−84
	NT2RP2006106 - Homo sapiens	1 . . . 164	154/164 (93%)
	(Human). 165 aa.
Q96G04	Similar to RIKEN cDNA	1 . . . 87	81/114 (71%)	2e−34
	5730409G15 gene - Homo	1 . . . 114	82/114 (71%)
	sapiens (Human). 330 aa.
Q9CS89	5730409G15Rik protein - Mus	1 . . . 87	62/114 (54%)	7e−22
	musculus (Mouse). 319 aa	1 . . . 114	68/114 (59%)
	(fragment).
Q96S85	Hypothetical 33.0 kDa protein -	1 . . . 54	50/54 (92%)	1e−20
	Homo sapiens (Human). 296 aa.	1 . . . 54	51/54 (93%)
QSX0Q4	Hypothetical 45.6 kDa protein -	114 . . . 163	18/52 (34%)	1.5
	Neurospora crassa. 420 aa.	36 . . . 87	26/52 (49%)

[0473] PFam analysis predicts that the NOV29a protein contains the domains shown in the Table 29E.

TABLE 29E
Domain Analysis of NOV29a
	Pfam	NOV29a	Identities/	Expect
	Domain	Match	Similarities	Value
		Region	for the Matched
			Region

Example 30

[0474] 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:71	1411 bp
NOV30a.	TTCTGATCATGTCACTGGCAAGGCAATGCTTACCTCACTTGGCCTGAAGTTGGGGGAT
CG134421-01
DNA Sequence	CGTGTTGTTATTGCAGGACAGAAGGTTGGTACATTAAGATTTTGTGGAACAACTGAAT
	TTGCAAGTGGGCAGTGGGCTGGCATTGAACTGGATGAACCAGAAGGAAAAAATAATGG
	AAGTCTTCCAAAAGTCCAGTACTTTAAATGTGCCCCCAAGTATGGTATTTTTGCACCT
	CTTTCAAACATAAGTAAAGCAAAACCTCGAAGCAAGAATATAACACACACTCCTTCTA
	CAAAACCTCCTGTACCTCTCATCAGCTCCCAGAAAATTGACCTACCTCATCTCACCTC
	AAAACTAAATACTGGATTAATCACATCAAAAAAAGATACTGCTTCTCAGTCAACACTT
	TCATTGCCTCCTGGTCAACAACTTAAAACTCTGACACACAAAGATCTTGCCCTCCTTC
	GATCTCTCACCACCTCCTCCTCTACATCTTCTTTGCAACACAGACACACCTACCCCAA
	GAAACAGAATGCAATCAGCAGTAACAAGAAGACAATGACCAAAACCCCTTCCCTTTCA
	TCCACAGCCAGTGCTGGTTTGAATTCCTCACCAACATCTACAGCAAATAATAGCCCTT
	GCCAGGCCGAACTCCGCCTCGGCAGACAGACTGTTACTCGTAGGACAGACACTCGCCA
	CCATTAGGTTCTTTGGGACAACAAACTTCGCTCCAGGATATTGGTATGGTATAGACCT
	TGAAAAACCCCATCCCAAGAATGATGGTTCAGTTCCACGTGTGCAGTATTTTAGCTCT
	TCTCCAAGATATGCAATATTTGCTCCCCCATCCAGCCTGCAAAOAGTAACAGATTCCC
	TGCATACCCTTTCAGAAATTTCTTCAAATAAACAGAACCATTCTTATCCTCCTTTTAG
	CACAAGTTTTAGCACAACTTCTGCTTCTTCCCAAAACGACATTAACACAACAAATCCT
	TTTTCCAAATCCAAACCTGCTTTGCCTCGCAGTTCGAGCAGCACCCCCACCGCACGTC
	GCATTCAACGCACCGTCAACCTCCACCAGGCGTCTCAGGTCCTCCTCACCAGCTCCAA
	TGACATCCCTACTCTTAGCTATCTGGCCCCCACTGACTTTGCTTCAGGTATCTCCCTT
	GCACTTCAGCTCCCAAGCCCCAAGCCAAAAAATCATGCGTCAGTGGGTGACAACCGCT
	ATTTCACCTCTAAGCCGAACCATGGAGTCTTAGTTCCACCGAGCAGACTGACCTATCC
	GGGAATTAATGCCTCAAAACTTCTGGATGACAATTCTTAAGCTTCTAAAATATTAAAT
	AACCTCAAATATATATATTTGCTGTAAATAAAGAGTCCATCCTAAATGGTTTACTTTA
	TTTAGCCATATTAAAATTT
	ORF Start: ATG at 26	ORF Stop: TAG at 701
	SEQ ID NO: 72	225 aa	MW at 23826.7 kD
	NOV30a.	MLTSLCLKLCDRVVTACQKVCTLRFCCTTEFASGQWAGIELDEPEGKNNCSVGKVQYP
	CG134421-01
	Protein Sequence	KCAPKYCTFAPLSKISKAKCRRKNTTHTPSTKAACPLIRSQKIDVAHVTSKVNTCLMT
		SKKDSASESTLSLPPCEELKTVTEKDVALLCSVSSCSSTSSLEHRQSYPKKQNAISSN
		KKTMSKSPSLSSRASAGLNSSATSTANNSRCECELPLCRESVSCRTETGHH

[0475] Further analysis of the NOV30a protein yielded the following properties shown in Table 30B.

TABLE 30B
Protein Sequence Properties NOV30a
PSort     0.6500 probability located in cytoplasm: 0.1000 probability
analysis: located in mitochondrial matrix space: 0.1000 probability
          located in lysosome (lumen): 0.0000 probability located in
          endo-plasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0476] A search of the NOV30a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 30C.

TABLE 30C
Geneseq Results for NOV30a
		NOV30a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAY93488	Amino acid sequence of a potassium	1..153	76/153 (49%)	4e−33
	channel interactor polypeptide—	108..252	97/153 (62%)
	Rattus sp. 267 aa. [WO200031133-
	A2, 02-JUN-2000]
ABB97353	Novel human protein SEQ ID NO:	1..147	75/147 (51%)	5e−32
	621—Homo sapiens, 547 aa.	288..426	95/147 (64%)
	[WO200222660-A2, 21-MAR-2002]
AAU74342	Human cytoskeleton-associated	1..147	75/147 (51%)	5e−32
	protein (CYSKP) #13—Homo	288..426	95/147 (64%)
	sapiens, 547 aa. [WO200185942-A2,
	15-NOV-2001]
ABG29271	Novel human diagnostic protein	1..64	64/64 (100%)	1e−31
	#29262—Homo sapiens, 574 aa.	293..356	64/64 (100%)
	[WO200175067-A2, 11-OCT-2001]
ABG29271	Novel human diagnostic protein	1..64	64/64 (100%)	1e−31
	#29262—Homo sapiens, 574 aa.	293..356	64/64 (100%)
	[WO200175067-A2, 11-OCT-2001]

[0477] In a BLAST search of public sequence datbases, the NOV30a protein was found to have homology to the proteins shown in the BLASTP data in Table 30D.

TABLE 30D
Public BLASTP Results for NOV30a
		NOV30a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96BR7	Hypothetical 53.2 kDa protein -	1 . . . 212	212/212 (100%)	e−116
	Homo sapiens (Human). 494 aa.	170 . . . 381	212/212 (100%)
Q9H7C0	CDNA: FLJ21069 fis, clone	1 . . . 212	211/212 (99%)	e−115
	CAS01594 - Homo sapiens	170 . . . 381	211/212 (99%)
	(Human). 492 aa.
Q96MA5	CDNA FLJ32705 fis. clone	1 . . . 192	44/192 (99%)	e−104
	TESTI2000600. weakly similar to	127 . . . 318	192/192 (99%)
	restin - Homo sapiens (Human).
	345 aa.
Q9D2L0	4833417L20Rik protein - Mus	1 . . . 212	167/212 (78%)	5e−88
	musculus (Mouse). 694 aa.	277 . . . 487	180/212 (84%)
Q9D3G0	5830409B12Rik protein - Mus	1 . . . 212	167/212 (78%)	5e−88
	musculus (Mouse). 488 aa.	61 . . . 271	180/212 (84%)

[0478] PFam analysis predicts that the NOV30a protein contains the domains shown in the Table 30E.

TABLE 30E
Domain Analysis of NOV30a
			Identities/
		NOV30a	Similarities
	Pfam	Match	for the Matched	Expect
	Domain	Region	Region	Value
	CAP_GLY	27. . . 69	27/43 (63%)	6.1e−22
			38/43 (88%)

Example 31

[0479] 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: 73	3974 bp
NOV31a.	GGTTCCTGAGCACTTACTTGCACACAGATTCAATGATGGAGGTATCAGCCCCACCATA
CG134895
DNA Sequence	GGAAGCTGAAATAGTAGTTTCCTTCATATTTCTGGACAGCCCCTCTGTGGGTGCAACA
	ACATTCCCTGACAAAGGTGCAGCCTCCATATGAAATCTGATCTTGGTCTGAGACAATG
	TCTTCTGCCCAGTTTCACTGGATGACTCTTGTCCCCTTTTTGTCCTGCCCCCTATCCA
	GGTCGTTTTCTGATGTGACGGCTGAGACATGAGATCTTCAGCCTCCAGGCTCTCCAGT
	TTTTCGTCGAGAGATTCACTATGGAATCGGATGCCGGACCAGATCTCTGTCTCGGAGT
	TCATCGCCGAGACCACCGAGGACTACAACTCGCCCACCACGTCCAGCTTCACCACGCG
	GCTGCACAACTGCAGGAACACCGTCACGCTGCTGGAGGAGGCTCTAGGCCAAGATAGA
	ACAGCCCTTCAGAAAGTGAAGAAGTCTGTAAAAGCAATATATAATTCTGGTCAAGATC
	ATGTACAAAATGAAGAAAACTATGCACAAGTTCTTGATAAGTTTGGGAGTAATTTTTT
	AAGTCGAGACAACCCCGACCTTGGCACCGCGTTTGTCAAGTTTTCTACTCTTACAAAG
	GAACTGTCCACACTGCTGAAAAATCTGCTCCAGGGTTTGAGCCACAATGTGATCTTCA
	CCTTGGATTCTTTGTTAAAAGGAGACCTAAAGGGAGTCAAAGGAGATCTCAAGAAGCC
	ATTTGACAAAGCCTGGAAAGATTATGAGACAAAGTTTACAAAAATTGAGAAAGAGAAA
	AGAGAGCACGCAAAACAACATGGGATGATCCGCACAGAGATAACAGGAGCTGAGATTG
	CGGAAGAAATGGAGAAGGAAAGGCGCCTCTTTCAGCTCCAAATGTGTGAATATCTCAT
	TAAAGTTAATGAAATCAAGACCAAAAAGGGTGTGGATCTGCTGCAGAATCTTATAAAG
	TATTACCATGCACAGTGCAATTTCTTTCAAGATGGCTTGAAAACAGCTGATAAGTTGA
	AACAGTACATTGAAAAACTGGCTGCTGATTTATATAATATAAAACAGACCCAGGATGA
	AGAAAAGAAACAGCTAACTGCACTCCGAGACTTAATAAAATCCTCTCTTCAACTGGAT
	CAGAAAGAATCTAGGAGAGATTCTCAGAGCCGGCAAGGAGGATACAGCATGCATCAGC
	TCCAGGGCAATAAGGAATATGGCAGTGAAAAGAAGGGGTACCTGCTAAAGAAAAGTGA
	CGGGATCCGGAAAGTATGGCAGAGGAGGAAGTGTTCAGTCAAGAATGGGATTCTGACC
	ATCTCACATGCCACATCTAACAGGCAACCAGCCAAGTTGAACCTTCTCACCTGCCAAG
	TAAAACCTAATGCCGAAGACAAAAAATCTTTTGACCTGATATCACATAATAGAACATA
	TCACTTTCAGGCAGAAGATGAGCAGGATTATGTAGCATGGATATCAGTATTGACAAAT
	AGCAAAGAAGAGGCCCTAACCATGGCCTTCCGTGGAGAGCAGAGTGCGGGAGAGAACA
	GCCTGGAAGACCTGACAAAAGCCATTATTGAGGATGTCCAGCGGCTCCCAGGGAATGA
	CATTTGCTGCGATTGTGGCTCATCAGAACCCACCTGGCTTTCAACCAACTTGGGTATT
	TTGACCTGTATAGAATGTTCTGGCATCCATAGGGAAATGGGGGTTCATATTTCTCGCA
	TTCAGTCTTTGGAACTAGACAAATTAGGAACTTCTGAACTCTTGCTGGCCAAGAATGT
	AGGAAACAATAGTTTTAATGATATTATGGAAGCAAATTTACCCAGCCCCTCACCAAAA
	CCCACCCCTTCAAGTGATATGACTGTACGAAAAGAATATATCACTGCAAAGTATGTAG
	ATCATAGGTTTTCAAGGAAGACCTGTTCAACTTCATCAGCTAAACTAAATGAATTGCT
	TGAGGCCATCAAATCCAGGGATTTACTTGCACTAATTCAAGTCTATGCAGAAGGGGTA
	GAGCTAATGGAACCACTGCTGGAACCTGGGCAGGAGCTTGGGGAGACAGCCCTTCACC
	TTGCCGTCCGAACTGCAGATCAGACATCTCTCCATTTGGTTGACTTCCTTGTACAAAA
	CTGTGGGAACCTGGATAAGCAGACGGCCCTGGGAAACACAGTTCTACACTACTGTAGT
	ATGTACAGTAAACCTGAGTGTTTGAAGCTTTTGCTCAGGAGCAAGCCCACTGTGGATA
	TAGTTAACCAGGCTGGAGAAACTGCCCTAGACATAGCAAAGAGACTAAAAGCTACCCA
	GTGTGAAGATCTGCTTTCCCAGGCTAAATCTGGAAAGTTCAATCCACACGTCCACGTA
	GAATATGAGTGGAATCTTCGACAGGAGGAGATAGATGAGAGCGATGATGATCTGGATG
	ACAAACCAAGCCCTATCAAGAAAGAGCGCTCACCCAGACCTCAGAGCTTCTGCCACTC
	CTCCAGCATCTCCCCCCAGGACAAGCTGGCACTGCCAGGATTCAGCACTCCAAGGGAC
	AAACAGCGGCTCTCCTATGGAGCCTTCACCAACCAGATCTTCGTTTCCACAAGCACAG
	ACTCGCCCACATCACCAACCACGGAGGCTCCCCCTCTGCCCCCTAGGAACGCCGGGAA
	AGGTCCAACTGGCCCACCTTCAACACTCCCTCTAAGCACCCAGACCTCTAGTGGCAGC
	TCCACCCTATCCAAGAAGAGGCCTCCTCCCCCACCACCCGGACACAAGAGAACCCTAT
	CCGACCCTCCCAGCCCACTACCTCATGGGCCCCCAAACAAAGGCGCAGTTCCTTGGGG
	TAACGATGGGGGTCCATCCTCTTCAAGTAAGACTACAAACAAGTTTGAGGGACTATCC
	CAGCAGTCGAGCACCAGTTCTGCAAAGACTGCCCTTGGCCCAAGAGTTCTTCCTAAAC
	TACCTCAGAAAGTGGCACTAAGGAAAACAGATCATCTCTCCCTAGACAAAGCCACCAT
	CCCGCCCGAAATCTTTCAGAAATCATCACAGTTGGCAGAGTTGCCACAAAAGCCACCA
	CCTGGAGACCTGCCCCCAAAGCCCACAGAACTGGCCCCCAAGCCCCAAATTGGAGATT
	TGCCGCCTAGGCCAGGAGAACTGCCCCCCAAACCACAGCTGGGGGACCTGCCACCCAA
	ACCCCAACTCTCAGACTTACCTCCCAAACCACAGATGAAGGACCTGCCCCCCAAACCA
	CAGCTGGGAGACCTGCTAGCAAAATCCCAGACTGGAGATGTCTCACCCAAGGCTCAGC
	AACCCTCTGAGGTCACACTGAAGTCACACCCATTGGATCTATCCCCAAATGTGCAGTC
	CAGAGACGCCATCCAAAAGCAAGCATCTGAAGACTCCAACGACCTCACGCCTACTCTG
	CCAGAGACGCCCGTACCACTGCCCAGAAAAATCAATACGGGGAAAAATAAAGTGAGGC
	GAGTGAAGACCATTTATGACTGCCAGGCAGACAACGATGACGAGCTCACATTCATCGA
	GGGAGAAGTGATTATCGTCACAGGGGAAGAGGACCAGGAGTGGTGGATTGGCCACATC
	GAAGGACAGCCTGAAAGGAAGGGGGTCTTTCCAGTGTCCTTTGTTCATATCCTGTCTG
	ACTAGCAAAACGCAGAACCTTAAGATTGTCCACATCCTTCATGCAAGACTGCTGCCTT
	CATGTAACCCTGGGCACAGTGTGTATATAGCTGCTGTTACAGAGTAAGAAACTCATGG
	AAGGGCCACCTCAGGAGGGGGATATAATGTGTGTTGTAAATATCCTGTGGTTTTCTGC
	CTTCACCAGTATGAGGGTAGCCTCGGACCCGGCGCGCCTTACTGGTTTGCCAAAGCCA
	TCCTTGGCATCTAGCACTTACATCTCTCTATGCTGTTCTACAAGCAAACAAACAAAAA
	TAGGAGTATAGGAACTGCTGGCTTTGCAAA
	ORF Start: ATG at 261	ORF Stop: TAG at 3657
SEQ ID NO: 74	1132 aa	MW at 125838.0 kD
NOV31a.	MRSSASRLSSFSSRDSLWNRMPDQISVSEFIAETTEDYNSPTTSSFTTRLHNCRNTVT
CG134895-01
Protein Sequence	LLEEALGQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFLSRDNPDLGT
	AFVKFSTLTKELSTLLKNLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYE
	TKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRLFQLQMCEYLIKVNEIKTKK
	GVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKLAADLYNIKQTQDEEKKQLTALR
	DLIKSSLQLDQKESRRDSQSRQGGYSMHQLQGNKEYGSEKKGYLLKKSDGIRKVWQRR
	KCSVKNGILTISHATSNRQPAKLNLLTCQVKPNAEDKKSFDLISHNRTYHFQAEDEQD
	YVAWISVLTNSKEEALTMAFRGEQSAGENSLEDLTKAIIEDVQRLPGNDICCDCGSSE
	PTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDIM
	EANLPSPSPKPTPSSDMTVRKEYITAKYVDHRFSRKTCSTSSAKLNELLEAIKSRDLL
	ALIQVYAEGVELMEPLLEPGQELGETALHLAVRTADQTSLHLVDFLVQNCGNLDKQTA
	LGNTVLHYCSMYSKPECLKLLLRSKPTVDIVNQAGETALDIAKRLKATQCEDLLSQAK
	SGKFNPHVHVEYEWNLRQEEIDESDDDLDDKPSPIKKERSPRPQSFCHSSSISPQDKL
	ALPGFSTPRDKQRLSYGAFTNQIFVSTSTDSPTSPTTEAPPLPPRNAGKGPTGPPSTL
	PLSTQTSSGSSTLSKKRPPPPPPGHKRTLSDPPSPLPHGPPNKGAVPWGNDGGPSSSS
	KTTNKFEGLSQQSSTSSAKTALGPRVLPKLPQKVALRKTDHLSLDKATIPPEIFQKSS
	QLAELPQKPPPGDLPPKPTELAPKPQIGDLPPKPGELPPKPQLGDLPPKPQLSDLPPK
	PQMKDLPPKPQLGDLLAKSQTGDVSPKAQQPSEVTLKSHPLDLSPNVQSRDAIQKQAS
	EDSNDLTPTLPETPVPLPRKINTGKNKVRRVKTIYDCQADNDDELTFIEGEVIIVTGE
	EDQEWWIGHIEGQPERKGVFPVSFVHILSD

[0480] Further analysis of the NOV31a protein yielded the following properties shown in Table 31B.

TABLE 31B
Protein Sequence Properties NOV31a
PSort     0.9200 probability located in mitochondrial matrix space:
analysis: 0.7466 probability located in nucleus; 0.6000 probability
          located in mitochondrial inner membrane: 0.6000 probability
          located in mitochondrial intermembrane space
SignalP   No Known Signal Sequence Predicted
analysis:

[0481] A search of the NOV31a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 31C.

TABLE 31C
Geneseq Results for NOV31a
		NOV31a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAW77286	Bovine differentiation enhancing	1..1132	1088/1135 (95%)	0.0
	factor 1 protein—Bos sp. 1129 aa.	1..1129	1106/1135 (96%)
	[WO9836065-A1, 20-AUG-1998]
AAM40068	Human polypeptide SEQ ID NO	193..1132	939/940 (99%)	0.0
	3213—Homo sapiens, 940 aa.	1..940	939/940 (99%)
	[WO200153312-A1, 26-JUL-
	2001]
AAW77287	Zebrafish differentiation	1..1132	879/1162 (75%)	0.0
	enhancing factor 1 protein—	1..1151	981/1162 (83%)
	Brachydanio rerio, 1151 aa.
	[WO9836065-A1, 20-AUG-1998]
AAW77290	Human differentiation enhancing	21..1132	619/1120 (55%)	0.0
	factor 2 gene—Homo sapiens,	1..1006	746/1120 (66%)
	1006 aa. [WO9836065-A1, 20-
	AUG-1998]
AAW77288	Zebrafish differentiation	21..853	540/842 (64%)	0.0
	enhancing factor 2 protein—	1..826	650/842 (77%)
	Brachydanio rerio, 982 aa.
	[WO9836065-A1, 20-AUG-1998]

[0482] In a BLAST search of public sequence datbases, the NOV31a protein was found to have homology to the proteins shown in the BLASTP data in Table 31D.

TABLE 31D
Public BLASTP Results for NOV31a
		NOV31a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9QWY8	ADP-ribosylation factor-directed	1 . . . 1132	1091/1147 (95%)	0.0
	GTPase activating protein isoform	1 . . . 1147	1109/1147 (96%)
	a - Mus musculus (Mouse). 1147
	aa.
O97902	Differentiation enhancing factor I -	1 . . . 1132	1089/1135 (95%)	0.0
	Bos taurus (Bovine). 1129 aa.	1 . . . 1129	1107/1135 (96%)
Q9Z2B6	ADP-ribosylation factor-directed	1 . . . 1132	1020/1147 (88%)	0.0
	GTPase activating protein isoform	1 . . . 1090	1045/1147 (90%)
	b - Mus musculus (Mouse). 1090
	aa.
Q9ULH1	KIAA1249 protein - Homo	184 . . . 1132	949/949 (100%)	0.0
	sapiens (Human). 949 aa	1 . . . 949	949/949 (100%)
	(fragment).
O43150	KIAA0400 protein - Homo	21 . . . 1132	619/1120 (55%)	0.0
	sapiens (Human). 1006 aa.	1 . . . 1006	746/1120 (66%)

[0483] PFam analysis predicts that the NOV31a protein contains the domains shown in the Table 31E.

TABLE 31E
Domain Analysis of NOV31a
			Identities/
			Similarities
		NOV31a	for the
	Pfam	Match	Matched	Expect
	Domain	Region	Region	Value
	PH	328 . . . 419	25/92 (27%)	2.8e−15
			67/92 (73%)
	ArfGap	442 . . . 565	51/139 (37%)	1.4e−35
			95/139 (68%)
	ank	603 . . . 638	10/36 (28%)	0.0045
			28/36 (78%)
	ank	639 . . . 671	10/33 (30%)	0.00026
			24/33 (73%)
	SH3	1073 . . . 1130	20/61 (33%)	4.7e−10
			43/61 (70%)

Example 32

[0484] 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:75	1739 bp
NOV32a,	ACCTGGCCCTACCTAAGCATGATCATGGAAAGCAAGTTCCGGGAGAAACTTGAGCCCA
CG134922-01
DNA Sequence	AGATCCGAGAGAAGAGCATCCACCTGAGCACCTTTACCTTTACCAAGCTCTACTTTGG
	ACAGAAGTCTCCCAGGGTCAACGGTGTCAAGGCACACACTAATACGTGCAACCGAAGA
	CGTCTGACTGTGGACCTGCAGATCTGCCCCAGCACCACCTGGGATGTAAGCAGTGGGG
	GCTGCTTCTGTGTCCCCATGAAAGACACCTGGGCAGAGATGGGACAGGGGGACAGCAG
	GGGTGGAAAAGTGGGCAGCGTGTTTACCAAGAGCCCCTCCTTTTCATCTTCAGGGTAT
	CGTGGGGTGAGCTACATCGGGGACTGTTATATCAGTGTGGAGCTGCAGAAGATTCATG
	CTGGTGTGAACGGGATCCAGGTGGGTGGAGCCCGGCGGGTCATCCTGGAGCCCCTCCT
	ATTGGACAAGCCCTTTGTGGGAGCCGTGACTGTGTTCTTCCTTCAGAAGCCGCCTAAT
	AGCTTCCCTCTGCCCCTGAAGCACCTACAGATCAACTGGACTGGCCTGACCAACCTGC
	TGGATGCGCCGGGAATCAATGATGTGTCAGACAGCTTACTGGAGGACCTCATTGCCAC
	CCACCTCGTGCTGCCCAACCGTGTGACTGTGCCTGTGAAGAAGGGGCTGGATCTGACC
	AACCTGCGCTTCCCTCTGCCCTGTGGGGTGATCAGAGTGCACTTGCTGGAGGCAGAGC
	AGCTGGCCCAGAAGGACAACTTTCTGGGGCTCCGAGGCAAGTCAGATCCCTACGCCAA
	GGTGAGCATCGGCCTACAGCATTTCCGGAGTAGGACCATCTACAGGAACCTGAACCCC
	ACCTGGAACGAAGTGTTCCAGTTCATGGTGTACGAAGTCCCTGGACAGGACCTGGAGG
	TAGACCTGTATGATGAGGATACCGACAGGGATGACTTCCTGGGCAGCCTGCAGATCTG
	CCTTGGAGATGTCATGACCAACAGAGTGGTGGATGAGTGGTTTGTCCTGAATGACACA
	ACCAGCGGGCGGCTGCACCTGCGGCTGGAGTGGCTTTCATTGCTTACTGACCAAGACG
	TTCTGACTGAGGACCATGGTGGCCTTTCCACTGCCATTCTCGTGGTCTTCTTGGAGAG
	TGCCTGCAACTTGCCGAGAAACCCTTTTGACTACCTGAATCGTGAATATCGAGCCAAA
	AAACTCTCCAGGTTTGCCAGAAACAAGGTCAGCAAAGACCCTTCTTCCTATGTCAAAC
	TATCTGTAGGCAAGAAGACACATACAAGTAAGACCTGTCCCCACAACAAGGACCCTGT
	GTGGAGCCAGGTGTTCTCCTTCTTTGTGCACAATGTGGCCACTGAGCGGCTCCATCTG
	AAGGTGCTTGATGATGACCAGGAGTGTGCTCTGGGAATGCTGGAGGTCCCCCTGTGCC
	AGATCCTCCCCTATGCTGACCTCACTCTTGAGCAGCGCTTTCAGCTGGACCACTCAGG
	CCTGGACAGCCTCATCTCCATGAGGCTGGTGCTTCGGGTAAACCTAACACCATGTACC
	AGCAGTGGAGCTGATCCCTACGTCCGTGTCTACTTGTTGCCACAAAGGAAGTGGGCAT
	GTCGTAAGAAGACTTCAGTGAAGCGGAAGACCTTGGAACCCCTGTTTGATGAGACGTA
	AGTGGGCTGGTGGCCTGCCTAGAGTGCCTCACCCATTCAAGTATTTTCCAAGTACCT
	ORF Start: ATG at 19	ORF Stop: TAA at 1681
	SEQ ID NO: 76	554 aa	MW at 62597.4 kD
NOV32a,	MIMESKFREKLEPKIREKSIHLRTFTFTKLYFGQKCPRVNGVKAHTNTCNRRRVTVDL
CG134922-01
Protein Sequence	QICPSSTWDVSSGGCFCVPMKDTWAEMGQGDSRGGKVGSVFTKSPSFSSSGYRCVSYI
	GDCYISVELQKIHAGVNGIQVGGARRVILEPLLLDKPFVGAVTVFFLQKPPNSFPLPL
	KHLQINWTGLTNLLDAPGINDVSDSLLEDLIATHLVLPNRVTVPVKKGLDLTNLRFPL
	PCGVIRVHLLEAEQLAQKDNFLGLRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVF
	QFMVYEVPGQDLEVDLYDEDTDRDDFLGSLQICLGDVMTNRVVDEWFVLNDTTSGRLH
	LRLEWLSLLTDQDVLTEDHGGLSTAILVVFLESACNLPRNPFDYLNGEYRAKKLSRFA
	RNKVSKDPSSYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDDD
	QECALGMLEVPLCQILPYADLTLEQRFQLDHSGLDSLISMRLVLRVNLTPCTSSGADP
	YVRVYLLPERKWACRKKTSVKRKTLEPLFDET

[0485] Further analysis of the NOV32a protein yielded the following properties shown in Table 32B.

TABLE 32B
Protein Sequence Properties NOV32a
PSort     0.4500 probability located in cytoplasm: 0.1523
analysis: probability located in microbody (peroxisome):
          0.1000 probability located in mitochondrial matrix
          space; 0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0486] 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 32G
Geneseq Results for NOV32a
		NOV32a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM40496	Human polypeptide SEQ ID NO	3 . . . 510	202/523 (38%)	8e−91
	5427 - Homo sapiens. 1131 aa.	174 . . . 622	296/523 (55%)
	[WO200153312-A1, 27-JUL-2001]
AAM40495	Human polypeptide SEQ ID NO	3 . . . 510	202/523 (38%)	8e−91
	5426 - Homo sapiens. 1131 aa.	174 . . . 622	296/523 (55%)
	[WO200153312-A1, 26-JUL-2001]
AAM38709	Human polypeptide SEQ ID NO	3 . . . 510	202/523 (38%)	8e−91
	1854 - Homo sapiens. 1114 aa.	157 . . . 605	296/523 (55%)
	[WO200153312-A1, 26-JUL-2001]
AAB94266	Human protein sequence SEQ ID	3 . . . 510	200/523 (38%)	4e−90
	NO: 14680 - Homo sapiens. 1104	157 . . . 595	292/523 (55%)
	aa. [EP1074617-A2. 07-Feb-2001]
AAB04766	Human vesicle trafficking protein-9	3 . . . 510	200/523 (38%)	4e−90
	(VETRP-9) protein - Homo sapiens.	157 . . . 595	292/523 (55%)
	1104 aa. [WO200146256-A2. 28-
	JUN-2001]

[0487] In a BLAST search of public sequence datbases, the NOV32a protein was found to have homology to the proteins shown in the BLASTP data in Table 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
BAA86542	KIAA1228 protein - Homo	3 . . . 510	214/523 (40%)	e−110
	sapiens (Human), 843 aa	135 . . . 576	316/523 (59%)
	(fragment).
Q9ULJ2	KIAA1228 protein - Homo	3 . . . 510	214/523 (40%)	e−110
	sapiens (Human). 724 aa	16 . . . 457	316/523 (59%)
	(fragment).
O94848	KIAA0747 protein - Homo	3 . . . 510	202/523 (38%)	2e−90
	sapiens (Human). 1072 aa	115 . . . 563	296/523 (55%)
	(fragment).
Q9BSJ8	Similar to membrane bound C2	3 . . . 510	200/523 (38%)	1e−89
	domain containing protein - Homo	157 . . . 595	292/523 (55%)
	sapiens (Human). 1104 aa.
Q91X62	Similar to membrane bound C2	3 . . . 510	200/523 (38%)	1e−88
	domain containing protein - Mus	147 . . . 585	287/523 (54%)
	musculus (Mouse). 1092 aa.

[0488] PFam analysis predicts that the NOV32a protein contains the domains shown in the Table 32E.

TABLE 32E
Domain Analysis of NOV32a
			Identities/
			Similarities
		NOV32a	for the
	Pfam	Match	Matched	Expect
	Domain	Region	Region	Value
	C2	237 . . . 321	33/98 (34%)	2.8e−16
			60/98 (61%)

Example 33

[0489] 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: 77	3084 bp
NOV33a,	GACCCTCTCCTGCAGAGGCAGAGGCCGCCTGCCACAGGCCACGCGGAGCAGGGTCCCA
CG135070-01
DNA Sequence	CCATGGCCCTGAGCATCTTGACTGAGCAGTTCTGCATCCCAAGGCCTCACAAGAAGCC
	CCCGAGCGCCCACAGCATGAAGGAGGAGGCCTTCCTCCGGCGCCGCTTCTCCCTGTGT
	CCACCTTCCTCCACCCCTCAGAAAGTCGACCCCCGGAAGCTCACCCGGAACTTGCTCC
	TCAGCGGAGACAATGAGCTCTACCCACTCAGCCCAGGGAAGGACATGGAGCCCAACGG
	CCCGTCGCTGCCCAGGGATGAAGGGCCCCCGACCCCAAGCTCTGCCACGAAGGTGCCA
	CCGGCAGAGTACAGGCTGTGCAACGGGTCAGACAAGGAATGTGTGTCCCCCACCGCCA
	GGGTCACCAAGAAGGAGACTCTCAAGGCGCAGAAGGAGAACTACCGGCAGGAGAAGAA
	GCGCGCCACACGGCAQCTGCTCAGCCCTCTGACAGACCCCAGCGTGGTCATCATCGCT
	GACAGCCTGAAGATCCGCGGCACCCTGAAGAGCTGGACCAAGCTGTGGTGCGTGCTGA
	AGCCGGGGGTGCTGCTCATCTACAAGACGCCCAAGGTGGGCCAGTGGGTGGGCACGGT
	GCTGCTGCACTGCTGCGAGCTCATCGAGCGGCCCTCCAAGAAGGACGGCTTCTGCTTC
	AAGCTCTTCCACCCGCTGGATCAGTCCGTCTGGGCCGTGAAGGGCCCCAAAGGTGAGA
	GCGTGGGCTCCATCACACAGCCCCTGCCCAGCAGCTACCTGATCTTCAGGGCCGCCTC
	CGAGTCAGATGGTCGCTGCTGGCTGGACGCCCTGGAGCTGGCCCTGCGCTGCTCTAGC
	CTACTGAGACTGGGCACCTGCAAGCCGGGCCGAGACGGGGAGCCAGGGACCTCGCCAG
	ACGCATCACCCTCATCGCTCTGTGGGCTGCCACCCTCAGCCACTGTCCACCCAGACCA
	AGACCTGTTCCCACTGAACGGGTCTTCCCTGGAGAACGATGCATTCTCAGACAAGTCG
	GAGAGAGAGAACCCTGAGGAGTCAGATACCGAGACCCAGGACCATAGCCGGAAGACGG
	AGAGTGGCAGCGACCAGTCAGAGACCCCTGGGGCCCCCGTGCGGAGAGGGACCACCTA
	TGTGGAGCAGGTCCAGGAGGAGCTGGGGGAGCTGGGCGAGGCGTCCCAGGTGGAGACA
	GTGTCAGAGGAGAACAAGAGTCTGATGTGGACCCTGCTGAAGCAGCTACGGCCAGGCA
	TGGACCTGTCCCGCGTGGTGCTACCCACGTTCGTACTGGAGCCGCGCTCCTTCCTGAA
	CAAGCTCTCCCACTACTACTACCACGCAGACCTGCTCTCCAGGGCTGCGGTGCAGGAG
	GATGCCTACAGCCGCATGAAGCTGGTGCTGCGGTGGTACCTGTCTGGCTTCTACAAGA
	AGCCCAAGGGAATCAACAAGCCGTACAACCCCATCCTGGGGGAGACCTTCCGCTGCTG
	CTGGTTCCACCCGCAGACTGACAGCCGCACATTCTACATAGCACAGCAGGTGTCCCAC
	CACCCGCCCGTGTCTGCCTTCCACGTCAGCAACCGGAAGGACGGCTTCTGCATCAGTG
	GCAGCATCACACCCAAGTCCAGGTTTTATGGGAACTCGCTGTCGGCCCTGCTGGACGG
	CAAAGCCACCCTCACCTTCCTGAACCGAGCCGAGGATTACACCCTTACCATGCCCTAC
	GCCCACTGCAAAGGAATCCTGTATGGCACGATGACCCTGGAGCTGGGTGGGAAGGTCA
	CCATCGAGTGTGCGAAGAACAACTTCCAGGCCCAGCTGGAATTCAAACTCAAGCCCTT
	CTTCGGGGGTAGCACCAGCATCAACCACATCTCGGGAAACATCACGTCGGGAGAGGAA
	GTCCTGGCGAGCCTCAGTGGCCACTGGGACAGGGACGTGTTTATCAAGGAGGAAGGGA
	GCGGAAGCAGTGCGCTTTTCTGGACCCCGAGCGGGGAGGTCCGCAGACACAGGCTGAG
	GCAGCACACGGTGCCGCTGGAGGGGCAGACGGAGCTGGAGTCCGAGACGCTCTGGCAG
	CACGTCACCAGGGCCATCAGCAAGGGCCACCAGCACAGGGCCACACAGGAGAAGTTTG
	CACTCCAGGAGCCACAGCGGCAGCGGGCCCGTGAGCCGGAGGAGAGCCTCATGCCCTG
	GAAGCCGCAGCTGTTCCACCTGGACCCCATCACCCAGGAGTGGCACTACCGATACGAG
	GACCACAGCCCCTGGGACCCCCTGAAGGACATCGCCCAGTTTGAGCAAGACGGGATCC
	TGCGGACCTTGCAGCAGGAGGCCGTGGCCCGCCAGACCACCTTCCTGGGCAGCCCAGG
	GCCCAGGCACGAGAGGTCTCGCCCAGACCAGCGGCTTCGCAAGGCCAGCGACCAGCCC
	TCCGGCCACAGCCAGGCCACGGAGAGCAGCGGATCCACGCCTGAGTCCTGCCCAGAGC
	TCTCAGACGAGGAGCAGGATGGTGACTTTGTCCCTGGCGGTCAGAGCCCATGCCCTCG
	GTGCAGGAACGAGGCGCGGCGGCTGCAGGCCCTGCACGAGCCCATCCTCTCCATCCGA
	GAGGCCCAGCAGGAGCTGCACAGGCACCTCTCGGCCATGCTGAGCTCCACGGCACGGG
	CAGCACAGGCACCGACCCCAGGCCTCCTGCAGAGCCCCCGATCCTGGTTCCTGCTCTG
	CGTGTTCCTGGCGTGTCAGCTGTTCATTAACCACATCCTCAAATAGGAGCCCTCCGGG
	CAGAGCTCCTGGCCGGTCCTGAGCCCTCCCTCCCAGGCACCCAGCACTTTAAGCCTGC
	TCCATGGAGGCAGAGAGGCCCGGCAAGCACAGCCACTGTGACGGGGAGTCCAGGCGCA
	GGAGGGACCCGGGGCCACAAGGCGCTGCGGGCCCAGGTGTGCTGGGCCCCTCTCAGGG
	GCACTGGCCTCTCTCCAGGGCCTTCCGCCCAGCGCTGGCCTTAATGCTAAAGCCAAAT
	GCAGCTTCTGCTGTGCGACCCACTCCTGGCCATCTTGCCGTGTCACCCCCTGTCCGGC
	CTCCACTTGC
	ORF Start: ATG at 61	ORF Stop: TAG at 2770
	SEQ ID NO: 78	903 aa	MW at 101214.4 kD
NOV33a.	MALSILTEQFCIPRPHKKPPSAHSMKEEAFLRRRFSLCPPSSTPQKVDPRKLTRNLLL
CG135070-01
Protein Sequence	SGDNELYPLSPGKDMEPNGPSLPRDECPPTPSSATKVPPAEYRLCNGSDKECVSPTAR
	VTKKETLKAQKENYRQEKKRATRQLLSALTDPSVVIMADSLKIRGTLKSWTKLWCVLK
	PGVLLIYKTPKVGQWVGTVLLHCCELIERPSKKDCFCFKLFHPLDQSVWAVKGPKGES
	VGSITQPLPSSYLIFRAASESDGRCWLDALELALRCSSLLRLGTCKPGRDGEPGTSPD
	ASPSSLCCLPASATVHPDQDLFPLNGSSLENDAFSDKSERENPEESDTETQDHSRKTE
	SGSDQSETPGAPVRRGTTYVEQVQEELGELGEASQVETVSEENKSLMWTLLKQLRPGM
	DLSRVVLPTFVLEPRSFLNKLSDYYYHADLLSRAAVEEDAYSRMKLVLRWYLSGFYKK
	PKGIKKPYNPILGETFRCCWFHPQTDSRTFYIAEQVSHHPPVSAFHVSNRKDGFCISG
	SITAKSRFYGNSLSALLDGKATLTFLNRAEDYTLTMPYAHCKGILYGTMTLELGGKVT
	IECAKNNFQAQLEFKLKPFPGGSTSINQISGKITSGEEVLASLSGHWDRDVFIKEEGS
	GSSALFWTPSGEVRRQRLRQHTVPLEGQTELESERLWQHVTRAISKGDQHRATQEKFA
	LEEAQRQRARERQESLMPWKPQLFHLDPITQEWHYRYEDHSPWDPLKDIAQFEQDGIL
	RTLQQEAVARQTTFLGSPGPRHERSGPDQRLRKASDQPSGHSQATESSGSTPESCPEL
	SDEEQDGDFVPGGESPCPRCRKEARRLQALHEAILSIREAQQELHRHLSANLSSTARA
	AQAPTPGLLQSPRSWFLLCVFLACQLFTNHILK

[0490] Further analysis of the NOV33a protein yielded the following properties shown in Table 33B.

TABLE 33B
Protein Sequence Properties NOV33a
PSort     0.8500 probability located in endoplasmic reticulum
analysis: (membrane); 0.7400 probability located in nucleus;
          0.4400 probability located in plasma membrane: 0.1000
          probability located in mitochondria inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0491] 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
		NOV32a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM40420	Human polypeptide SEQ ID NO	70 . . . 903	828/834 (99%)	0.0
	3565 - Homo sapiens. 842 aa.	9 . . . 842	830/834 (99%)
	[W0200153312-A1, 26-JUL-2001]
AAM42204	Human polypeptide SEQ ID NO	224 . . . 903	676/680 (99%) 0.0
	7135 - Homo sapiens. 690 aa.	11 . . . 690	679/680 (99%)
	[WO200153312-A1, 26-JUL-2001]
ABB61239	Drosophila melanogaster	142 . . . 749	337/612 (55%)	0.0
	polypeptide SEQ ID NO 10509 -	1 . . . 595	436/612 (71%)
	Drosophila melanogaster. 762 aa.
	[WO200171042-A2, 27-SEP-2001]
AAB98084	Human protein sequence SEQ ID	406 . . . 903	268/498 (53%)	e−155
	NO:110 - Homo sapiens. 472 aa.	1 . . . 472	350/498 (69%)
	[WO200130972-A2, 03-May-2001]
AAB98083	Human brain eDNA library protein	406 . . . 792	244/387 (63%)	e−149
	sapiens. 385 aa. [WO200130972-	1 . . . 383	304/387 (78%)
	A2, 03-May-2001]

[0492] In a BLAST search of public sequence datbases, the NOV33a protein was found to have homology to the proteins shown in the BLASTP data in Table 33D.

TABLE 33D
Public BLASTP Results for NOV33a
		NOV33a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9H0X9	Oxysterol binding protein-related	25 . . . 903	878/879 (99%)	0.0
	protein 5 (OSBP-related protein 5)	1 . . . 879	878/879 (99%)
	(ORP-5) - Homo sapiens (Human).
	879 aa.
Q9ER64	Oxysterol binding protein-related	25 . . . 903	744/880 (84%)	0.0
	protein 5 (OSBP-related protein 5)	1 . . . 874	794/880 (89%)
	(ORP-5) (Oxystyrol-binding protein
	homologue 1) - Mus musculus
	(Mouse), 874 aa.
Q8R510	Oxysterol binding protein	25 . . . 903	743/880 (84%)	0.0
	homologue 1 - Mus musculus	1 . . . 874	794/880 (89%)
	(Mouse). 874 aa.
BAA95975	KIAA1451 protein - Homo sapiens	41 . . . 903	484/892 (54%)	0.0
	(Human). 954 aa (fragment).	97 . . . 954	624/892 (69%)
Q8WXP8	Oxysterol-binding protein-like	41 . . . 903	484/892 (54%)	0.0
	protein OSBPL8 - Homo sapiens	32 . . . 889	624/892 (69%)
	(Human). 889 aa.

[0493] PFam analysis predicts that the NOV33a protein contains the domains shown in the Table 33E.

TABLE 33E
Domain Analysis of NOV33a
	NOV33a	Identities/
Pfam	Match	Similarities	Expect
Domain	Region	for the Matched Region	Value
PH	151 . . . 267	29/117 (25%)	2.3e−13
		86/117 (74%)
Oxysterol_BP	362 . . . 778	118/447 (26%)	1.3e−55
		258/447 (58%)

Example 34

[0494] 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: 79	1905 bp
NOV34a.	GTCGACGCGGCCGCGCTGCGTCCAGCATTGGATATTTGTCAGGAATGCAGATACCCTG
CG172478-01
DNA Sequence	AAGGGAACACAACAATGGTCCAAGGGGGTTTCCCAGAAAAAATCAGACAAAGATATGC
	AGATCTGCCTGGAGAACTGCACATTATTGAACTTGAAAAAGATAAGAATGGACTTGGA
	CTCAGCCTTGCTGGTAATAAAGACCGATCACGCATGAGCATATTTGTGGTGGGAATTA
	ACCCGGAAGGACCTGCTGCCGCAGATGGACGAATGCATATTGGAGATGAACTCTTAGA
	GATAAACAATCAGATTCTGTATGGAAGAAGTCACCAAAATGCATCTGCCATTATTAAG
	ACTGCCCCATCAAAGGTCAAGCTGGTTTTCATCAGAAACGAGGATGCAGTCAATCAGA
	TGGCCGTTACTCCCTTTCCAGTGCCATCAAGTTCTCCATCTTCTATTGAGGATCAGAG
	CGGCACCGAACCTATTAGTAGTGAGGAAGATGGCAGCCTCGAAGTTGGTATTAAACAA
	TTGCCTGAAAGTGAAAGCTTCAAACTGGCTGTCAGCCAGATGAAACAGCAAAAATATC
	CAACAAAAGTCTCCTTCAGTTCACAAGAGATACCATTAGCACCAGCTTCATCATACCA
	TTCAACAGATCCAGACTTCACAGGCTATGGTGGTTTCCAGGCTCCTCTGTCAGTGGAC
	CCCGCAACGTGTCCCATTGTCCCTGGACAGGAAATGATTATAGAAATATCCAAGGGAC
	GTTCAGGGCTTGGTCTCAGCATTGTGGGAGGAAAAGACACACCCTTGTTCTGGAGGCT
	GGGAAGTCCAAGAGCATGGAGCCAGCATCTGGTGAGGGCCTTCATGCTGCATCATCCT
	GTGACAGAAGTTCAAGGGCAAAATGCTATAGTTATCCATGAAGTCTATGAAGAAGGGG
	CAGCAGCCAGAGATGGAAGACTTTGGGCTGGTGACCAGATATTAGAGGTTAATGGGGT
	TGACCTGAGGAACTCCAGCCACGAAGAAGCCATCACAGCCCTGAGGCAGACCCCCCAG
	AAGGTGCGGCTGGTGGTGTATAGAGATGAGGCACACTACCGGGATGAGGAGAACTTGG
	AGATTTTCCCTGTGGATCTGCAGAAGAAAGCTGGCCGGGGCCTGGGCCTGAGCATCGT
	TGGGAAACGGAATGGAAGCGGAGTGTTTATTTCTGACATCGTGAAAGGCGGAGCCGCA
	GACCTGGATGGGAGATTGATTCAGGGAGATCAGATCTTATCTCTGAATGGGGAGGACA
	TGAGAAATCCCTCACAGCAGACAGTGGCCACCATCCTCAAGTGTGCACAGGGACTTGT
	GCAGCTAGAGATTGGAAGACTCCGAGCTGGTTCCTGGACCTCCGCAACCACGACATCA
	CAGAACAGTCAGGGTAGTCAGCAGAGTGCACACAGCAGCTGTCATCCCTCCTTCGCTC
	CTGTCATCACTGGCCTGCAAAACCTGGTTGCCACAAAAAGAGTTTCAGATCCTTCCCA
	GAAAACAGATATGGAACCAAGGACTGTTGAGATAAACAGGGAGCTCAGTGATGCCCTT
	GGAATCAGTATTGCTGGAGGAAGAGGAAGTCCCTTAGGAGATATCCCCGTATTTATTG
	CCATGATTCAGGCTAGCGGAGTGGCCGCACGGACACAGAAGCTTAAAGTAGGAGATCG
	GATTGTCAGCATTAACGGGCAACCTTTGGATGGGCTGTCTCACGCGGATGTGGTTAAT
	CTGCTGAAGAACGCCTACGGGCGCATTATCCTGCAGGTAGTAGCAGATACCAATATAA
	GCGCCATAGCAGCTCAGCTTGAAAACATGTCTACAGGCTACCACCTTGGTTCGCCCAC
	TGCTGAACACCATCCAGAAGACACAGAGTGAGTATTTCAGATGCAGAGG
	ORF Start: ATG at 73	ORF Stop TGA at 1885
	SEQ ID NO: 80	604 aa	MW at 64963.5 kD
NOV34a.	MVQCCFPEKIRQRYADLPGELHIIELEKDKNGLGLSLAGNKDRSRMSIFVVGINPEGP
CG172478-01
Protein Sequence	AAADGRMHIGDELLEINNQILYGRSHQNASAIIKTAPSKVKLVFIRNEDAVNQMAVTP
	FPVPSSSPSSIEDQSGTEPISSEEDCSLEVGIKQLPESESFKLAVSQMKQQKYPTKVS
	FSSQEIPLAPASSYHSTDADFTGYGGFQAPLSVDPATCPIVPGQEMIIEISKGRSGLG
	LSIVGGKDTRLFWRLGSPRAWSQHLVRAFMLHHPVTEVEGQNAIVIHEVYEEGAAARD
	GRLWAGDQILEVNGVDLRNSSHEEAITALRQTPQKVRLVVYRDEAHYRDEENLEIFPV
	DLQKKAGRGLGLSIVGKRNGSGVFISDIVKCGAADLDGRLIQGDQILSVNGEDMRNAS
	QETVATILKCAQGLVQLEIGRLRAGSWTSARTTSQNSQGSQQSAHSSCHPSFAPVITG
	LQNLVGTKRVSDPSQKTDMEPRTVEINRELSDALGISIAGGRGSPLGDIPVFTAMIQA
	SGVAARTQKLKVGDRIVSINGQPLDGLSHADVVNLLKNAYGRIILQVVADTNISAIAA
	QLENMSTGYHLGSPTAEHHPEDTE

[0495] Further analysis of the NOV34a protein yielded the following properties shown in Table 34B.

TABLE 34B
Protein Sequence Properties NOV34a
PSort     0.6500 probability located in cytoplasm: 0.1000
analysis: probability located in mitochondrial matrix space:
          0.1000 probability located in lysosome (lumen);
          0.0000 probability located in endoplasmic reticulum
          (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0496] A search of the NOV34a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 34C.

TABLE 34C
Geneseq Results for NOV34a
		NOV34a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY24025	Amino acid sequence of the human	8 . . . 604	566/600 (94%)	0.0
	MMSC1 protein - Homo sapiens.	1224 . . . 1793	567/600 (94%)
	1881 aa. [WO9936566-A1. 22
	Jul. 1999]
ABG06117	Novel human diagnostic protein	8 . . . 409	400/402 (99%)	0.0
	#6108 - Homo sapiens. 1627 aa.	1226 . . . 1627	401/402 (99%)
	[WO200175067-A2. 11 Oct.
	2001]
ABG06117	Novel human diagnostic protein	8 . . . 409	400/402 (99%)	0.0
	#6108 - Homo sapiens. 1627 aa.	1226 . . . 1627	401/402 (99%)
	[WO200175067-A2. 11 Oct.
	2001]
ABG07290	Novel human diagnostic protein	8 . . . 366	357/359 (99%)	0.0
	#7281 - Homo sapiens. 1584 aa.	1226 . . . 1584	358/359 (99%)
	[WO200175067-A2. 11 Oct.
	2001]
ABG07290	Novel human diagnostic protein	8 . . . 366	357/359 (99%)	0.0
	#7281 - Homo sapiens. 1584 aa.	1226 . . . 1584	358/359 (99%)
	[WO200175067-A2. 11 Oct.
	2001]

[0497] In a BLAST search of public sequence datbases, the NOV34a protein was found to have homology to the proteins shown in the BLASTP data in Table 34D.

TABLE 34D
Public BLASTP Results for NOV34a
		NOV34a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
AAM28433	PalsI-associated tight junction	8 . . . 604	563/600 (93%)	0.0
	protein - Homo sapiens (Human),	1224 . . . 1793	566/600 (93%)
	1801 aa.
O70471	Channel interacting PDZ domain	1 . . . 604	492/636 (77%)	0.0
	protein - Mus musculus (Mouse).	1 . . . 604	518/636 (81%)
	612 aa.
Q9H3N9	PDZ domain protein 3′ variant 4 -	8 . . . 455	410/453 (90%)	0.0
	Homo sapiens (Human). 1134 aa.	683 . . . 1105	413/453 (90%)
O43742	InadI protein - Homo sapiens	8 . . . 366	357/359 (99%)	0.0
	(Human), 1582 aa.	1224 . . . 1582	358/359 (99%)
Q8WU78	Similar to channel-interacting	274 . . . 604	331/334 (99%)	0.0
	PDZ domain protein - Homo	5 . . . 338	331/334 (99%)
	sapiens (Human). 346 aa
	(fragment).

[0498] PFam analysis predicts that the NOV34a protein contains the domains shown in the Table 34E.

TABLE 34E
Domain Analysis of NOV34a
		Identities/
		Similarities
Pfam	NOV34a Match	for the Matched
Domain	Region	Region	Expect Value
PDZ	23 . . . 105	31/86 (36%)	5.7e−14
		63/86 (73%)
PDZ	219 . . . 333	40/116 (34%)	2.8e−20
		89/116 (77%)
PDZ	347 . . . 428	34/84 (40%)	3.5e−18
		67/84 (80%)
PDZ	487 . . . 572	26/88 (30%)	6.7e−13
		65/88 (74%)

Example 35

[0499] 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: 81	1563 bp
NOV35a.	ACCAGTTTTTCCCCAGCACCACCATCAAGGCCTCGAGGCTCCCACCTCCCTCTACAGC
CG172549-01
DNA Sequence	CTGTGGACTCACTTAGGGAATCCCGAACGATGACAGAAAAGGAGGTGCTGGAGTCCCC
	TAAGCCCTCCTTCCCAGCAGAGACTCGGCAAACTGGGCTACAGCGGCTAAAGCAGTTA
	CTCAGGAAGGGTTCTACAGGGACAAAGGAGATGGAACTTCCCCCAGAGCCCCAGGCCA
	ATGGGGAGGCAGTGGGAGCTGGGGGTGGGCCCATCTACTACATCTATGAGGAAGAGGA
	AGAGGAAGAAGAGGAGGAGGAGGAGCCACCCCCAGAACCTCCTAAGCTGGTCAACGAT
	AAGCCCCACAAATTCAAAGATCACTTCTTCAAGAAGCCAAAGTTCTGTGATGTCTGTG
	CCCGGATGATTGTTCTCAACAACAAGTTTGGGCTTCGCTGTAAGAACTGCAAAACCAA
	CATCCATGAACACTGTCAGTCCTATGTGGAAATGCAGAGATGCTTCGGCAAGATCCCA
	CCTGGTTTCCATCGGGCCTATAGTTCCCCACTCTACAGCAACCAGCAGTACGCTTGTG
	TCAAAGATCTCTCTGCTGCCAATCGCAATGATCCTGTGTTTGAAACCCTGCGCACTGG
	GGTGATCATGGCAAACAAGGAACGGAAGAAGGGACAGGCAGATAAGAAAAATCCTGTA
	GCAGCCATGATGGAGGAGGAGCCAGAGTCGGCCAGACCAGACGAAGGCAAACCCCAGG
	ATGGAAACCCTGAAGGGGATAACAAGGCTGAGAAGAAGACACCTGATGACAAGCACAA
	GCAGCCTGGCTTCCAGCAGTCTCATTACTTTGTGGCTCTCTATCGGTTCAAAGCCCTG
	GAGAAGGACGATCTCGATTTCCCGCCAGGAGAGAAGATCACAGTCATTGATCACTCCA
	ATGAAGAATGGTGGCGGGGGAAAATCGGGGAGAAGGTCGGATTTTTCCCTCCAAACTT
	CATCATTCGGGTCCGGGCTGGAGAACGTGTGCACCGCGTGACCAGATCCTTCGTGGGG
	AACCGCGAGATAGGGCAGATCACTCTCAAGAAGGACCAGATCGTGGTGCAGAAAGGAG
	ACGAAGCGGGCGGCTACGTCAAGGTCTACACCGGCCGCAAGGTGGGGCTGTTTCCCAC
	CGACTTTCTAGAGGAAATTTAGGCGTGCGGGCGCCTGCAAGCGGGAGACACCCACACC
	CCATTCTGGGCGGGCCCAGTGGAGTTTGGGGAGGGGGGCGAAAGCAACGGGACTGCTG
	GGAGAGGAGGGGTAGGAAGGCCCGCCTGAGCGCGACGGGGCTTCCGGGAAGGGACTGG
	TTCTCGCCCCCTTCCCCAGCCTGGGGCCTCGGATACCTGCTGCCCAGAGCAGCCCGGA
	CCCGAAACCTTTCAGGCCCCGCTTGCAAGAGCTGGAAAAAAACGCGTATCTACTAGGA
	GGAGCCAGGGACTGGGGCGGGGGGCGGGGGCGAGGGAGGGCGAACTGTCGAATGTTGC
	GAATTTATTAAACTTTTGACAAAACTTAAAAAAAAAAAAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 88	ORF Stop: TAG at 1180
	SEQ ID NO: 82	364 aa	MW at 41506.7 kD
NOV35a.	MTEKEVLESPKPSFPAETRQSGLQRLKQLLRKGSTGTKEMELPPEPQANGEAVGAGGG
CG172549-01
Protein Sequence	PIYYIYEEEEEEEEEEEEPPPEPPKLVNDKPHKFKDHFFKKPKFCDVCARMIVLNNKF
	GLRCKNCKTNIHEHCQSYVEMQRCFGKIPPGFHRAYSSPLYSNQQYACVKDLSAANRN
	DPVFETLRTGVIMANKERKKGQADKKNPVAANMEEEPESARPEEGKPQDGNPEGDKKA
	EKKTPDDKHKQPGFQQSHYFVALYRFKALEKDDLDFPPGEKITVIDDSNEEWWRGKIG
	EKVGFFPPNFIIRVRAGERVHRVTRSFVGNREIGQITLKKDQIVVQKGDEAGGYVKVY
	TGRKVGLFPTDFLEEI
	SEQ ID NO: 83	1563 bp
NOV35b.	ACCACTTTTTCCCCAGCACCACCATCAAGGCCTCGAGGCTCCCAGCTCCCTCTACAGC
CG172549-02
DNA Sequence	CTGTGGACTGACTTAGGGAATCCCGAACGATGACAGAAAAGGAGGTGCTGGAGTCCCC
	TAAGCCCTCCTTCCCAGCAGAGACTCGGCAAAGTGGGCTACAGCGGCTAAAGCAGTTA
	CTCAGGAAGGGTTCTACAGGGACAAAGGAGATGGAACTTCCCCCAGAGCCCCAGGCCA
	ATGGGGAGGCAGTGGGAGCTGGGGGTGGGCCCATCTACTACATCTATGAGGAAGAGGA
	AGAGGAAGAAGAGGAGGAGGAGGAGCCACCCCCAGAACCTCCTAAGCTGGTCAACGAT
	AAGCCCCACAAATTCAAAGATCACTTCTTCAAGAAGCCAAAGTTCTGTGATGTCTGTG
	CCCGGATGATTGTTCTCAACAACAAGTTTGGGCTTCGCTGTAAGAACTGCAAAACCAA
	CATCCATGAACACTGTCAGTCCTATGTGGAAATGCAGAGATGCTTCGGCAAGATCCCA
	CCTGGTTTCCATCGGGCCTATAGTTCCCCACTCTACAGCAACCAGCAGTACGCTTGTG
	TCAAAGATCTCTCTGCTGCCAATCGCAATGATCCTGTGTTTGAAACCCTGCCCACTGG
	GGTGATCATGGCAAACAAGGAACGGAAGAAGGGACAGGCAGATAAGAAAAATCCTGTA
	GCAGCCATGATGGAGGAGGAGCCAGAGTCGGCCAGACCAGAGGAAGGCAAACCCCAGG
	ATGGAAACCCTGAAGGGGATAAGAAGGCTGAGAAGAAGACACCTGATGACAAGCACAA
	GCAGCCTGGCTTCCAGCAGTCTCATTACTTTGTGGCTCTCTATCGGTTCAAAGCCCTG
	GAGAAGGACGATCTGGATTTCCCGCCAGGAGAGAACATCACAGTCATTGATGACTCCA
	ATGAAGAATGGTGGCGGGGGAAAATCGGGGAGAAGGTCGCATTTTTCCCTCCAAACTT
	CATCATTCGGGTCCGGGCTGGAGAACGTGTGCACCGCGTGACGAGATCCTTCCTGGGG
	AACCGCGAGATAGGGCAGATCACTCTCAAGAAGGACCAGATCCTGGTGCAGAAAGGAG
	ACGAAGCGGGCGGCTACGTCAAGGTCTACACCGGCCGCAAGGTGGGGCTGTTTCCCAC
	CGACTTTCTAGAGGAAATTTAGGCGTGCGGGCGCCTGCAAGCGGGAGACACCCACACC
	CCATTCTGGGCGGGCCCAGTGGAGTTTGGGGAGGGGGGCGAAAGCAACGGGACTGCTG
	GGAGAGGAGGGGTAGGAAGGCCCGCCTGAGCGCGACGGGGCTTCCGGGAAGGGACTGG
	TTCTCGCCCCCTTCCCCAGCCTGGGGCCTCGGATACCTGCTGCCCAGAGCAGCCCGGA
	CCCGAAACCTTTCAGGCCCCGCTTGCAAGAGCTGGAAAAAAACGCGTATCTACTAGGA
	GGAGCCAGGGACTGGGGCGGGGGGCGGGGGCGAGGGAGGGCGAACTGTCGAATGTTGC
	GAATTTATTAAACTTTTGACAAAACTTAAAAAAAAAAAAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 88	ORF Stop: TAG at 1180
	SEQ ID NO: 84	364 aa	MW at 41506.7 kD
NOV35b,	MTEKEVLESPKPSFPAETRQSGLQRLKQLLRKGSTGTKEMELPPEPQANGEAVGAGGG
CG172549-02
Protein Sequence	PIYYIYEEEEEEEEEEEEPPPEPPKLVNDKPHKFKDHFFKKPKFCDVCARMIVLNNKF
	GLRCKNCKTNIHEHCQSYVEMQRCFGKIPPGFHRAYSSPLYSNQQYACVKDLSAANRN
	DPVFETLRTGVIMANKERKKGQADKKNPVAAMMEEEPESARPEEGKPQDGNPEGDKKA
	EKKTPDDKHKQPGFQQSHYFVALYRFKALEKDDLDFPPGEKITVIDDSNEEWWRGKIG
	EKVGFFPPNFIIRVRAGERVHRVTRSFVGNREIGQITLKKDQIVVQKGDEAGGYVKVY
	TGRKVGLFPTDFLEEI

[0500] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 35B.

TABLE 35B
Comparison of NOV35a against NOV35b.
			Identities/
		NOV35a Residues/	Similarities
		Match	for the
	Protein Sequence	Residues	Matched Region
	NOV35b	1 . . . 364	315/364 (86%)
		1 . . . 364	315/364 (86%)

[0501] Further analysis of the NOV35a protein yielded the following properties shown in Table 35C.

TABLE 35C
Protein Sequence Properties NOV35a
PSort     0.3000 probability located in nucleus: 0.1000
analysis: probability located in mitochondrial matrix space:
          0.1000 probability located in lysosome (lumen):
          0.0000 probability located in endoplasmic
          reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0502] 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
		NOV32a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAU27731	Mouse full-length polypeptide	1 . . . 364	364/364 (100%)	0.0
	sequence #56 - Mus musculus, 364	1 . . . 364	364/364 (100%)
	aa. [WO200164834-A2. 07-SEP-2001]
AAU27903	Mouse contig polypeptide	112 . . . 302	188/44 (98%)	e-111
	sequence #56 - Mus musculus, 227	33 . . . 223	189/44 (98%)
	aa. [WO200164834-A2. 07-SEP-2001]
AAW59642	Amino acid sequence of human	4 . . . 364	143/398 (35%)	1e-61
	Stac protein - Homo sapiens, 402	17 . . . 402	209/398 (51%)
	aa. [JP10175998-A. 30-JUN-1998]
AAW59641	Amino acid sequence of mouse	86 . . . 364	123/301 (40%)	2e-60
	Stac protein - Mus sp. 403 aa.	105 . . . 403	177/301 (57%)
	[JP10175998-A. 30-JUN-1998]
AAM82743	Human immune/haematopoietic	129 . . . 235	100/107 (93%)	3e-55
	antigen SEQ ID NO:10336 - Homo	3 . . . 109	104/107 (96%)
	sapiens, 153 aa. [WO200157182-
	A2. 09-AUG-2001]

[0503] In a BLAST search of public sequence datbases, the NOV35a protein was found to have homology to the proteins shown in the BLASTP data in Table 35E.

TABLE 35E
Public BLASTP Results forNOV35a
		NOV35a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96MF2	CDNA FLJ32451 fis. clone	1 . . . 364	364/364 (100%)	0.0
	SKMUS2001668. weakly similar to	1 . . . 364	364/364 (100%)
	neuron-specific signal trunduction
	protein Stac - Homo sapiens
	(Human). 364 aa.
Q96HU5	Similar to src homology three (SH3)	40 . . . 364	325/325 (100%)	0.0
	and cysteine rich domain - Homo	1 . . . 325	325/325 (100%)
	sapiens (Human). 325 aa.
Q99469	Stac protein (SRC homology 3 and	4 . . . 364	143/398 (35%)	3e−61
	cysteine-rich domain protein) -	17 . . . 402	209/398 (51%)
	Homo sapiens (Human). 402 aa.
Q8WUK8	Src homology three (SH3) and	4 . . . 364	143/398 (35%)	6e−61
	cysteine rich domain - Homo	17 . . . 402	208/398 (51%)
	sapiens (Human). 402 aa.
P97306	Stac protein (SRC homology 3 and	86 . . . 364	123/301 (40%)	4e−60
	cysteine-rich domain protein) - Mus	105 . . . 403	177/301 (57%)
	musculus (Mouse), 403 aa.

[0504] PFam analysis predicts that the NOV35a protein contains the domains shown in the Table 35F.

TABLE 35F
Domain Analysis of NOV35a
		Identities/
		Similarities
	NOV35a Match	for the Matched
Pfam Domain	Region	Region	Expect Value
DC1	101 . . . 132	11/47 (23%)	0.16
		21/47 (45%)
DAG_PE-bind	90 . . . 140	21/52 (40%)	1.1e−10
		41/52 (79%)
SH3	250 . . . 304	22/58 (38%)	1.8e−14
		43/58 (74%)

Example 36

[0505] 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: 85	442 bp
NOV36a.	CCGGCGGCTGTTGTCGGGCCTCCAGCGGGCGGGGCCGTTGGCGGAGCAGAGCGGAGGC
CG59828-01
DNA Sequence	GCACCCGGGCGGAGGGCCCACGAGGGCTCAGCCTTCCCGGTCAGCGGTCCTGACGGTA
	TCCCAGAGTGCCAGAGAACCGTTGCTTTTCCGAGTTGCTCTTCTTCCAGGCTCCGTTG
	GTGGTCCGCATGGCCCGTGGAAATCAACGAGAACTTGCCCGCCAGAAAAACATGAAGA
	AAACCCAGGAAATTAGCAAGGGAAAGAGGAAAGAGGATAGCTTGACTGCCTCTCAGAG
	AAAGCAGAGTTCTGGAGGCCAGAAATCTGAGAGCAAGATCTCAGCTGGGCCACACCTC
	CCTCTGAAGGCTCCAAGGGAGAATCCTTGCTTTCCTCTTCCAGCTGCTGGTGGCTCCA
	GGTATTACTTGGCTTATGGCAGCATAACTCCTATCTCTGCCTTTGTCTTTGTGGTCTT
	CTTTTCTGTCTTCTTCCCTTCTTTTTATGAGCACTTTTGCTGTTGGATTTAGGTTCCA
	TTCTAACCTAGGATGATCTCATTTGGAAATCCTTAATTTCATCTACAAAAACTGTTTT
	CCCAAATAGGTCACATTCACGCATATCAGATGGACAGATGTATCATTTTGGGGTCCAC
	CATTCAACCCACTACAAGGAGTTTTTTAAACAAAAATAGGAAACTTAGATGTAACTTA
	GCACTTTTTTTTTTTTTTTTTGAGATGGAGTCTCACTCTGTCACCAGACTGGAGTGCA
	GTGGCGCCATCTCAGCTCCATGCAACCTCTGCCTCCTGGGTTCAACCAGTTCTCTTGC
	CTCAGCCTCCTGGGTAGCTGGGATTACAGGCACGCGCTGCCACACCCAGGTAATTTAT
	TTATTTTTTTTTTGAGACAGAGTCTCGCACTGTTGCCCAGGCTGGACTGCAGTGGCGT
	GATCTCTGCTCACTGCAACCTCCGCCTCCCGGGTTCAAGCGATTCTCCAGCCTCAGCT
	TCCTGAGTAGATGGGATTACAGGCGCCTGCCACCACGCCCAGCTAATTTTTTTGTATT
	CTTAGTAGACATGGGGTTTCACCATGTTGGCCAGGCTGGTCTCCATCTCCTCACCTCG
	TGATTCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGTCACAGCCCC
	CGGCCATAATTTAGCACTTTAAAAAATAATAGCCATGTTGGGCCAGCCGTGGTGGCTC
	ATGCCTGTAATCTGAGCACTTTCGCAGACCAAGGCGGGTAGATCCCTTGTGCCCAGGA
	GTTCAAGACCAGCCTGGGCAACATGGCGAAACCCCATTTCTACTAAAAATACAAAAAT
	TAGCTGGGGCGAGGGGATAGGCCGAGTTCCGGGTGTAAGGGGGCCATTAGGGAGAGCA
	GAGCGAGGCAGCTGATCTTCCGGATTGGGGGCCTTGCCCGGAAGCTGGACCTCACGGA
	GATGAAACGGAAGATGCACCAGGATATGATCTCCATACAGAACTTTCTCATCTACGTG
	GCCCTGCTGCGAGTCACTCCATTTATCTTAAAGAAATTGGACAGCATATGAAGATTGG
	ACATCACATGTGAATGCATGATATGAACAGCCTGGTTACAGTTTCTACTGTTCTCTGC
	AAGTAAATAGGCCCACAAAGGTATAAGAGACTCTTTGAATCCACATAAAAATTCTGCT
	TGTTAAGAACAAGTTGAGCTCTGGTAACTGATCTTAATAGCTAAAATATAAAAATATT
	TGGGAAGTCTGAAATCAGGTCTCCTGGCCCTGGTGTGCCCTTAATGCCTGTGACAGTT
	GGCCTCTGTGAATATTGGTATAATTGTAAATAATGTCAAACTCCATTTTCTACCAAGT
	ATTAATTAAGGGAAGTATGTCTCAGAAATGGCAAAAAAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 184	ORF Stop: TAG at 514
	SEQ ID NO: 86	110 aa	MW at 12349.1 kD
NOV36a.	MARCNQRELARQKNMKKTQEISKGKRKEDSLTASQRKQSSCCQKSESKMSAGPHLPLK
CG59828-01
Protein Sequence	APRENPCFPLPAAGGSRYYLAYGSITPISAFVFVVFFSVFFPSFYEDFCCWI
	SEQ ID NO 87	255 bp
NOV36b.	GGATCCGCCCGTGGAAATCAACGAGAACTTGTCCGCCAGAAAAACATGAAGAAAACCC
172146552 DNA
Sequence	AGGAAATTAGCAAGGGAAAGAGGAAAGAGGATAGCTTGACTCCCTCTCAGAGAAAGCA
	GAGTTCTCGAGGCCACAAATCTCACAGCAACATGTCAGCTGGGCCACACCTCCCTCTG
	GAGGCTCCAAGGGAGAATCCTTGCTTTCCTCTTCCAGCTGCTGGTGGCTACAGGTATT
	ACTTGCCTTATGGCAGCCTCGAG
	ORF Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 88	85 aa	MW at 9368.5 kD
NOV36b.	GSARGNQRELVRQKNMKKTQETSKGKRKEDSLTASQRKQSSCGQKSESKMSAGPHLPL
172146552
Protein Sequence	EAPRENPCFPLPAAGGYRYYLAYGSLE

[0506] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 36B.

TABLE 36B
Comparison of NOV36a against NOV36b.
			Identities/
		NOV36a Residues/	Similarities
		Match	for the
	Protein Sequence	Residues	Matched Region
	NOV36b	2 . . . 69	49/68 (72%)
		3 . . . 70	50/68 (73%)

[0507] Further analysis of the NOV36a protein yielded the following properties shown in Table 36C.

TABLE 36C
Protein Sequence Properties NOV36a
PSort     0.8500 probability located in endoplasmic reticulum
analysis: (membrane): 0.5852 probability located in microbody
          (peroxisome): 0.4400 probability located in plasma
          membrane; 0.1000 probability located in mitochondrial
          inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0508] A search of the NOV36a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 36D.

TABLE 36D
Geneseq Results for NOV36a
			Identities/
		NOV36a	Similarities
		Residues/	for the
Geneseq	Protein/Organism/Length [Patent	Match	Matched	Expect
Identifier	#, Date]	Residues	Region	Value
ABG20531	Novel human diagnostic protein	4 . . . 51	37/48 (77%)	8e−13
	#20522 - Homo sapiens. 121 aa.	63 . . . 110	39/48 (81%)
	[WO200175067-A2, 11 Oct. 2001]
ABG20531	Novel human diagnostic protein	4 . . . 51	37/48 (77%)	8e−13
	#20522 - Homo sapiens. 121 aa.	63 . . . 110	39/48 (81%)
	[WO200175067-A2, 11 Oct. 2001]
ABG20532	Novel human diagnostic protein	1 . . . 63	36/63 (57%)	6e−11
	#20523 - Homo sapiens, 104 aa.	25 . . . 86	45/63 (71%)
	[WO200175067-A2, 11 Oct. 2001]
ABG20532	Novel human diagnostic protein	1 . . . 63	36/63 (57%)	6e−11
	#20523 - Homo sapiens. 104 aa.	25 . . . 86	45/63 (71%)
	[WO200175067-A2. 11 Oct. 2001]
AAU29730	Novel human secreted protein #221 -	40 . . . 90	31/51 (60%)	8e−11
	Homo sapiens. 71 aa.	10 . . . 60	37/51 (71%)
	[WO200179449-A2. 25 Oct. 2001]

[0509] In a BLAST search of public sequence datbases, the NOV36a protein was found to have homology to the proteins shown in the BLASTP data in Table 36E.

TABLE 36E
Public BLASTP Results for NOV36a
		NOV36a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O75920	Small EDRK-rich factor 1, long	1 . . . 110	110/110 (100%)	5e−60
	isoform - Homo sapiens (Human),	1 . . . 110	110/110 (100%)
	110 aa.
O75919	Small EDRK-rich factor 1, short	1 . . . 51	40/51 (78%)	4e−14
	isoform (Small EDRK-rich factor	1 . . . 51	42/51 (81%)
	1A) (Telomeric) - Homo sapiens
	(Human). 62 aa.
O88892	4F5 (Small EDRK-rich factor 1) -	1 . . . 38	37/38 (97%)	2e−13
	Mus musculus (Mouse). 62 aa.	1 . . . 38	38/38 (99%)
O75918	Small EDRK-rich factor 2 - Homo	1 . . . 38	26/38 (68%)	2e−07
	sapiens (Human). 59 aa.	1 . . . 38	31/38 (81%)
Q9VEW2	CG17931 protein - Drosophila	1 . . . 37	24/37 (64%)	2e−05
	melanogaster (Fruit fly). 60 aa.	1 . . . 36	29/37 (77%)

[0510] PFam analysis predicts that the NOV36a protein contains the domains shown in the Table 36F.

TABLE 36F
Domain Analvsis of NOV36a
Pfam Domain	NOV36a Match Region	Identities/	Expect
		Similarities	Value
		for the
		Matched Region

Example B

Sequencing Methodology and Identification of NOVX Clones

[0511] 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 tissues 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.

[0512] 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.

[0513] 3. PathCalling™ Technology: The NOVX nucleic acid sequences are derived by laboratory screening of cDNA library by the two-hybrid approach, cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, are sequenced. In silico prediction was based on sequences available in CuraGen Corporation's proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.

[0514] The laboratory screening was performed using the methods summarized below:

[0515] 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).

[0516] 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 event 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.

[0517] 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).

[0518] 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.

[0519] 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 as 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.

[0520] The cDNA coding for the CG122759-02 sequence was cloned by Polymerase Chain Reaction as described using the primers:

5′-CTGATGGAGCACCTTGTTCCCAC-3′    SEQ ID NO: 188
5′-CTACCTGAGGGTCTTCCAGCTGTCTTTT-3′ SEQ ID NO: 189

[0521] The cDNA coding for the CG125414-02 sequence was cloned by Polymerase Chain Reaction as described using the primers:

5′-ATGGAAGGAGACTTCTCGGTGTG-3′  SEQ ID NO: 190
5′-CATCACCTTTCACAAGACCACCAC-3′ SEQ ID NO: 191

[0522] 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.

[0523] 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

[0524] 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), A1_comprehensive_panel (containing normal tissue and samples from autoinflammatory diseases), Panel CNSD.01 (containing samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer's diseased brains).

[0525] 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.

[0526] First, the RNA samples were normalized to reference nucleic acids such as constitutively expressed genes (for example, β-actin and GAPDH). Normalized RNA (5 μl) 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.

[0527] 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.

[0528] Probes and primers were designed for each assay according to Applied Biosystems Primer Express Software package (version 1 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.

[0529] 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.

[0530] 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.

[0531] Panels 1, 1.1, 1.2, and 1.3D

[0532] 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.

[0533] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:

[0534] ca.=carcinoma.

[0535] *=established from metastasis,

[0536] met=metastasis.

[0537] s cell var=small cell variant.

[0538] non-s=non-sm=non-small.

[0539] squam=squamous.

[0540] pl. eff=pl effusion=pleural effusion.

[0541] glio=glioma.

[0542] astro=astrocytoma, and

[0543] neuro=neuloblastoma.

[0544] General_screening_panel_v1.4, v1.5 and v1.6

[0545] The plates for Panels 1.4, 1.5, and 1.6 include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panels 1.4, 1.5, and 1.6 are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in Panels 1.4, 1.5, and 1.6 are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on Panels 1.4, 1.5, and 1.6 are comprised of pools of samples derived from all major organ systems from 2 to 5 different adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose. Abbreviations are as described for Panels 1, 1.1, 1.2, and 1.3D.

[0546] Panels 2D, 2.2, 2.3 and 2.4

[0547] The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include 2 control wells and 94 test samples composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute's Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI) or from Ardais or Clinomics). The tissues are derived from human malignancies and in cases where indicated manly malignant tissues have “matched margins” obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted “NAT” in the results below. The tumor tissue and the “matched margins” are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues without malignancy (normal tissues) were also obtained from Ardais or Clinomics. This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, Calif.), Research Genetics, and Invitrogen.

[0548] HASS Panel v 1.0

[0549] The HASS panel v 1.0 plates are comprised of 93 cDNA samples and two controls. Specifically, 81 of these samples are derived from cultured human cancer cell lines that had been subjected to serum starvation, acidosis and anoxia for different time periods as well as controls for these treatments, 3 samples of human primary cells, 9 samples of malignant brain cancer (4 medulloblastomas and 5 glioblastomas) and 2 controls. The human cancer cell lines are obtained from ATCC (American Type Culture Collection) and fall into the following tissue groups: breast cancer, prostate cancer, bladder carcinomas, pancreatic cancers and CNS cancer cell lines. These cancer cells are all cultured under standard recommended conditions. The treatments used (serum starvation, acidosis and anoxia) have been previously published in the scientific literature. The primary human cells were obtained from Clonetics (Walkersville, Md.) and were grown in the media and conditions recommended by Clonetics. The malignant brain cancer samples are obtained as part of a collaboration (Henry Ford Cancer Center) and are evaluated by a pathologist prior to CuraGen receiving the samples. RNA was prepared from these samples using the standard procedures. The genomic and chemistry control wells have been described previously.

[0550] ARDAIS Panel v 1.0

[0551] The plates for ARDAIS panel v 1.0 generally include 2 control wells and 22 test samples composed of RNA isolated from human tissue procured by surgeons workings in close cooperation with Ardais Corporation. The tissues are derived from human lung malignancies (lung adenocarcinoma or lung squamous cell carcinoma) and in cases where indicated many malignant samples have “matched margins” obtained from noncancerous lung tissue just adjacent to the tumor. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue) in the results below. The tumor tissue and the “matched margins” are evaluated by independent pathologists (the surgical pathologists and again by a pathologist at Ardais). Unmatched malignant and non-malignant RNA samples from lungs were also obtained from Ardais. Additional information from Ardais provides a gross histopathological assessment of tumor differentiation grade and stage. Moreover, most samples include the original surgical pathology, report that provides information regarding the clinical state of the patient.

[0552] Panel 3D, 3.1 and 3.2

[0553] The plates of Panel 3D, 3.1, and 3.2 are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma of the tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D, 3.1, 3.2, 1, 1.1, 1.2, 1.3D, 1.4, 1.5, and 1.6 are of the most common cell lines used in the scientific literature.

[0554] Panels 4D, 4R, and 4.1D

[0555] 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.).

[0556] 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.

[0557] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells ere prepared from these cells by culture in DMEM 5% FCS (Hyclone). 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.). 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2×106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10−5M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.

[0558] 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.

[0559] 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.

[0560] 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.

[0561] 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.

[0562] 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.

[0563] For these cell lines and blood cells, RNA was prepared by lysing approximately 107 cells/ml using Trizol (Gibco BRL). Briefly, 1/10 volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 5 μl DTT. 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with 1/10 volume of 3M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at −80° C.

[0564] A1_comprehensive panel_v1.0

[0565] The plates for A1_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.

[0566] 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.

[0567] 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.

[0568] 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.

[0569] Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD as 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.

[0570] In the labels employed to identify tissues in the A1_comprehensive panel_v1.0 panel, the following abbreviations are used:

[0571] AI=Autoimmunity

[0572] Syn=Synovial

[0573] Normal=No apparent disease

[0574] Rep22/Rep20=individual patients

[0575] RA=Rheumatoid arthritis

[0576] Backus=From Backus Hospital

[0577] OA=Osteoarthritis

[0578] (SS) (BA) (MF)=Individual patients

[0579] Adj=Adjacent tissue

[0580] Match control=adjacent tissues

[0581] -M=Male

[0582] -F=Female

[0583] COPD=Chronic obstructive pulmonary disease

[0584] Panels 5D and 5I

[0585] 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.

[0586] In the Gestational Diabetes study subjects are young (18-40 years), otherwise health women with and without gestational diabetes undergoing routine (elective) Caesareyan 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:

[0587] Patient 2: Diabetic Hispanic, overweight, not on insulin

[0588] Patient 7-9: Nondiabetic Caucasian and obese (BMI>30)

[0589] Patient 10: Diabetic Hispanic, overweight, on insulin

[0590] Patient 11: Nondiabetic African American and overweight

[0591] Patient 12: Diabetic Hispanic on insulin

[0592] Adiocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr. 2, 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:

[0593] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0594] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated

[0595] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0596] 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.

[0597] Panel 51 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 51.

[0598] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:

[0599] GO Adipose=Greater Omentum Adipose

[0600] SK=Skeletal Muscle

[0601] UT=Uterus

[0602] PL=Placenta

[0603] AD=Adipose Differentiated

[0604] AM=Adipose Midway Differentiated

[0605] U=Undifferentiated Stem Cells

[0606] Panel CNSD.01

[0607] 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.

[0608] 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.

[0609] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:

[0610] PSP=Progressive supranuclear palsy

[0611] Sub Nigra=Substantia nigra

[0612] Glob Palladus=Globus palladus

[0613] Temp Pole=Temporal pole

[0614] Cing Gyr=Cingulate gyrus

[0615] BA 4 =Brodman Area 4

[0616] Panel CNS_Neurodegeneration_V1.0

[0617] The plates for Panel CNS_Neurodegeneration_V1.0 include to 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.

[0618] 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.

[0619] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:

[0620] AD=Alzheimer's disease brain: patient was demented and showed AD-like pathology upon autopsy

[0621] Control=Control brains: patient not demented, showing no neuropathology

[0622] Control (Path)=Control brains: pateint not demented but showing sever AD-like pathology

[0623] SupTemporal Ctx=Superior Temporal Cortex

[0624] Inf Temporal Ctx=Inferior Temporal Cortex

[0625] A. CG102071-01: MAP KINASE PHOSPHATASE-LIKE PROTEIN

[0626] Expression of full length physical clone CG102071-01 as assessed using the primer-probe set Ag6814, described in Table AA.

TABLE AA
Probe Name Ag6814
Primers	Sequences	Length	Start Position	SEQ ID No
Forward	5′-tgatggcaaaggaactggat-3′	20	339	89
Probe	TET-5′-ccataccccattgaaatcgtgcca-3′-TAMRA	24	368	90
Reverse	5′-aatcttggggtcacaggctt-3′	20	420	91

[0627] CNS_neurodegeneration_v1.0 Summary: Ag6814 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0628] General_screening_panel_v1.6 Summary: Ag6814 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0629] Panel 4.1D Summary: Ag6814 Expression of this gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)

[0630] B. CG112767-01 and CG112767-02: Cyclin

[0631] Expression of gene CG112767-01 and full length physical clone CG112767-02 was assessed using the primer-probe set Ag4461, described in Table BA. Results of the RTQ-PCR runs are shown in Tables BB, BC, BD and BE. Please note that CG112767-02 represents a full-length physical clone of the CG112767-01 gene, validating the prediction of the gene sequence.

TABLE BA
Probe Name Ag4461
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggtttgacagatctggaatgtg-3′	22	27	92
Probe	TET-5′-ctattcctccgcagtctggcctgtct-3′-TAMRA	26	54	93
Reverse	5′-gctggcaaagaagacagaaag-3′	21	81	94

[0632]

TABLE BB
CNS_neurodcgeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4461,		Ag4461,
Tissue Name	Run 224621596	Tissue Name	Run 224621596
AD 1 Hippo	54.7	Control (Path) 3 Temporal Ctx	12.9
AD 2 Hippo	3.7	Control (Path) 4 Temporal Ctx	8.8
AD 3 Hippo	8.6	AD 1 Occipital Ctx	11.3
AD 4 Hippo	8.1	AD 2 Occipital Ctx (Missing)	0.0
AD 5 hippo	52.9	AD 3 Occipital Ctx	35.4
AD 6 Hippo	100.0	AD 4 Occipital Ctx	7.7
Control 2 Hippo	10.7	AD 5 Occipital Ctx	9.2
Control 4 Hippo	0.0	AD 6 Occipital Ctx	27.9
Control (Path) 3 Hippo	28.3	Control 1 Occipital Ctx	0.0
AD 1 Temporal Ctx	7.6	Control 2 Occipital Ctx	15.9
AD 2 Temporal Ctx	19.5	Control 3 Occipital Ctx	0.0
AD 3 Temporal Ctx	0.0	Control 4 Occipital Ctx	0.0
AD 4 Temporal Ctx	0.0	Control (Path) 1 Occipital Ctx	16.7
AD 5 Inf Temporal Ctx	26.4	Control (Path) 2 Occipital Ctx	0.0
AD 5 Sup Temporal Ctx	45.4	Control (Path) 3 Occipital Ctx	0.0
AD 6 Inf Temporal Ctx	93.3	Control (Path) 4 Occipital Ctx	18.2
AD 6 Sup Temporal Ctx	13.5	Control 1 Parietal Ctx	15.3
Control 1 Temporal Ctx	9.0	Control 2 Parietal Ctx	13.4
Control 2 Temporal Ctx	0.0	Control 3 Parietal Ctx	8.7
Control 3 Temporal Ctx	0.0	Control (Path) 1 Parietal Ctx	5.4
Control 4 Temporal Ctx	0.0	Control (Path) 2 Parietal Ctx	13.3
Control (Path) 1 Temporal Ctx	15.9	Control (Path) 3 Parietal Ctx	0.0
Control (Path) 2 Temporal Ctx	46.7	Control (Path) 4 Parietal Ctx	18.4

[0633]

TABLE BC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4461,		Ag4461,
Tissue Name	Run 222523507	Tissue Name	Run 222523507
Adipose	0.6	Renal ca. TK-10	7.2
Melanoma* Hs688(A).T	0.1	Bladder	1.7
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	7.2
Melanoma* M14	2.9	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	1.0	Colon ca. SW-948	0.7
Melanoma* SK-MEL-5	5.5	Colon ca. SW480	12.3
Squamous cell carcinoma SCC-4	1.1	Colon ca.* (SW480 met) SW620	12.4
Testis Pool	8.2	Colon ca. HT29	5.3
Prostate ca.* (bone met) PC-3	27.9	Colon ca. HCT-116	3.8
Prostate Pool	0.6	Colon ca. CaCo-2	19.3
Placenta	1.0	Colon cancer tissue	1.9
Uterus Pool	0.0	Colon ca. SW1116	3.3
Ovarian ca. OVCAR-3	13.7	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	23.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	34.9	Colon Pool	0.4
Ovarian ca. OVCAR-5	23.8	Small Intestine Pool	1.8
Ovarian ca. IGROV-1	2.3	Stomach Pool	2.1
Ovarian ca. OVCAR-8	9.1	Bone Marrow Pool	1.3
Ovary	2.7	Fetal Heart	9.3
Breast ca. MCF-7	6.0	Heart Pool	0.0
Breast ca. MDA-MB-231	28.3	Lymph Node Pool	4.0
Breast ca. BT 549	1.1	Fetal Skeletal Muscle	3.3
Breast ca. T47D	27.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	2.7	Spleen Pool	3.6
Breast Pool	2.0	Thymus Pool	2.4
Trachea	1.2	CNS cancer (glio/astro) U87-MG	0.0
Lung	2.1	CNS cancer (glio/astro) U-118-MG	0.6
Fetal Lung	34.6	CNS cancer (neuro: met) SK-N-AS	11.9
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	2.4
Lung ca. LX-1	18.7	CNS cancer (astro) SNB-75	11.7
Lung ca. NCI-H146	2.4	CNS cancer (glio) SNB-19	2.3
Lung ca. SHP-77	15.1	CNS cancer (glio) SF-295	30.1
Lung ca. A549	16.5	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	100.0
Lung ca. NCI-H23	1.5	Brain (fetal)	6.9
Lung ca. NCI-H460	20.4	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	9.6	Cerebral Cortex Pool	0.3
Lung ca. NCI-H522	2.4	Brain (Substantia nigra) Pool	1.7
Liver	0.0	Brain (Thalamus) Pool	1.2
Fetal Liver	1.7	Brain (whole)	9.4
Liver ca. HepG2	2.6	Spinal Cord Pool	1.0
Kidney Pool	0.8	Adrenal Gland	5.6
Fetal Kidney	13.2	Pituitary gland Pool	0.3
Renal ca. 786-0	2.5	Salivary Gland	4.4
Renal ca. A498	6.7	Thyroid (female)	0.5
Renal ca. ACHN	6.0	Pancreatic ca. CAPAN2	16.6
Renal ca. UO-31	7.1	Pancreas Pool	2.3

[0634]

TABLE BD
Panel 4.1D
	Rel.			Rel.
	Exp. (%)			Exp. (%)
	Ag4461,	Rel. Exp. (%)		Ag4461,	Rel. Exp. (%)
	Run	Ag4461, Run		Run	Ag4461, Run
Tissue Name	44579104	195509495	Tissue Name	44579104	195509495
Secondary Th1 act	0.0	0.0	HUVEC IL-1beta	10.4	4.0
Secondary Th2 act	1.3	1.1	HUVEC IFN	7.3	9.5
			gamma
Secondary Tr1 act	0.0	0.0	HUVEC TNF	5.5	3.2
			alpha + IFN
			gamma
Secondary Th1 rest	0.0	0.0	HUVEC TNF	2.2	4.8
			alpha + IL4
Secondary Th2 rest	0.0	0.0	HUVEC IL-11	20.3	5.8
Secondary Tr1 rest	1.4	0.0	Lung Microvascular	37.9	9.3
			EC none
Primary Th1 act	0.0	0.0	Lung Microvascular	8.4	6.3
			EC TNFalpha + IL-
			1beta
Primary Th2 act	0.0	0.0	Microvascular	18.4	8.6
			Dermal EC none
Primary Tr1 act	0.0	0.0	Microsvasular	1.2	0.8
			Dermal EC
			TNFalpha + IL-
			1beta
Primary Th1 rest	0.0	0.0	Bronchial	19.6	8.0
			epithelium
			TNFalpha +
			IL1beta
Primary Th2 rest	0.3	0.0	Small airway	3.3	2.3
			epithelium none
Primary Tr1 rest	0.0	0.0	Small airway	17.0	4.8
			epithelium
			TNFalpha + IL-
			1beta
CD45RA CD4	1.2	1.9	Coronery artery	1.5	1.0
lymphocyte act			SMC rest
CD45RO CD4	0.0	0.0	Coronery artery	2.1	0.0
lymphocyte act			SMC TNFalpha +
			IL-1beta
CD8 lymphocyte act	0.0	1.8	Astrocytes rest	10.9	2.3
Secondary CD8	0.0	0.0	Astrocytes	5.0	7.3
lymphocyte rest			TNFalpha + IL-
			1beta
Secondary CD8	0.0	0.0	KU-812 (Basophil)	0.0	0.0
lymphocyte act			rest
CD4 lymphocyte	1.3	0.9	KU-812 (Basophil)	0.0	0.0
none			PMA/ionomycin
2ry	2.5	0.5	CCD1106	27.9	11.4
Th1/Th2/Tr1_anti-			(Keratinocytes)
CD95 CH11			none
LAK cells rest	1.2	0.0	CCD1106 (Keratinocytes)	18.4	3.4
			TNFalpha + IL-
			1 beta
LAK cells IL-2	4.5	3.3	Liver cirrhosis	1.2	0.0
LAK cells IL-2 + IL-	5.3	0.9	NCI-H292 none	12.2	7.8
12
LAK cells IL-	6.0	0.0	NCI-H292 IL-4	10.2	19.5
2 + IFN gamma
LAK cells IL-2 + IL-	3.5	2.1	NCI-H292 IL-9	20.7	6.8
18
LAK cells	3.9	0.0	NCI-H292 IL-13	7.2	4.1
PMA/ionomycin
NK Cells IL-2 rest	33.9	26.8	NCI-H292 IFN	14.3	0.0
			gamma
Two Way MLR 3	6.0	6.1	HPAEC none	14.6	8.4
day
Two Way MLR 5	2.5	0.0	HPAEC	5.7	8.1
day			TNF alpha +
			IL-1 beta
Two Way MLR 7	0.0	0.0	Lung fibroblast	4.9	1.0
day			none
PBMC rest	0.0	0.0	Lung fibroblast	2.7	0.0
			TNF alpha + IL-1
			beta
PBMC PWM	0.0	0.0	Lung fibroblast IL-4	1.2	0.0
PBMC PHA-L	1.7	0.0	Lung fibroblast IL-	2.6	0.9
			9
Ramos (B cell) none	0.0	0.0	Lung fibroblast IL-	3.8	1.1
			13
Ramos (B cell)	0.0	0.0	Lung fibroblast IFN	1.3	0.9
ionomycin			gamma
B lymphocytes	0.0	0.0	Dermal fibroblast	0.0	0.0
PWM			CCD1070 rest
B lymphocytes	0.0	0.0	Dermal fibroblast	2.7	0.0
CD40L and IL-4			CCD1070 TNF
			alpha
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	1.2	1.8
			CCD1070 IL-1 beta
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	0.0	0.0
PMA/ionomycin			IFN gamma
Dendritic cells none	0.0	0.8	Dermal fibroblast	0.0	4.6
			IL-4
Dendritic cells LPS	0.0	0.9	Dermal Fibroblasts	0.0	3.8
			rest
Dendritic cells anti-	0.0	0.0	Neutrophils	1.3	5.6
CD40			TNFa + LPS
Monocytes rest	0.0	0.0	Neutrophils rest	100.0	57.4
Monocytes LPS	0.0	0.0	Colon	2.6	1.1
Macrophages rest	0.0	0.9	Lung	5.0	16.8
Macrophages LPS	0.0	0.0	Thymus	19.1	25.7
HUVEC none	8.7	5.2	Kidney	14.9	100.0
HUVEC starved	29.3	12.9

[0635]

TABLE BE
general oncology screening panel_v_2.4
	Rel. Exp.		Rel. Exp.
	(%) Ag4461,		(%) Ag4461,
	Run		Run
Tissue Name	268672303	Tissue Name	268672303
Colon cancer 1	4.0	Bladder NAT 2	0.0
Colon NAT 1	7.0	Bladder NAT 3	0.0
Colon cancer 2	7.0	Bladder NAT 4	0.0
Colon NAT 2	5.7	Prostate	7.6
		adenocarcinoma 1
Colon cancer 3	5.6	Prostate	0.0
		adenocarcinoma 2
Colon NAT 3	8.0	Prostate	0.0
		adenocarcinoma 3
Colon malignant	4.4	Prostate	12.9
cancer 4		adenocarcinoma 4
Colon NAT 4	16.2	Prostate NAT 5	1.7
Lung cancer 1	30.4	Prostate	0.0
		adenocarcinoma 6
Lung NAT 1	11.4	Prostate	1.1
		adenocarcinoma 7
Lung cancer 2	34.9	Prostate	0.0
		adenocarcinoma 8
Lung NAT 2	15.1	Prostate	4.6
		adenocarcinoma 9
Squamous cell	16.6	Prostate NAT 10	1.8
carcinoma 3
Lung NAT 3	0.0	Kidney cancer 1	23.5
Metastatic	17.3	Kidney NAT 1	4.0
melanoma 1
Melanoma 2	0.0	Kidney cancer 2	100.0
Melanoma 3	0.0	Kidney NAT 2	38.7
Metastatic	32.3	Kidney cancer 3	2.6
melanoma 4
Metastatic	34.6	Kidney NAT 3	7.7
melanoma 5
Bladder cancer 1	0.0	Kidney cancer 4	0.0
Bladder NAT 1	0.0	Kidney NAT 4	0.0
Bladder cancer 2	4.6

[0636] CNS_neurodegeneration_v1.0 Summary: Ag4461 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.

[0637] General_screening_panel_v1.4 Summary: Ag4461 Highest expression of this gene is seen in the cerebellum (CT=28.7). This expression in the cerebellum suggests that the protein encoded by this gene may be a useful and specific target of drugs for the treatment of CNS disorders that have this brain region as the site of pathology, such as autism and the ataxias.

[0638] This gene is also widely expressed in this panel in the samples derived from cancer cell lines, with moderate to low expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0639] Among tissues with metabolic function, this gene is expressed at low but significant levels in adrenal gland, pancreas, and fetal skeletal muscle, heart, and liver. This 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.

[0640] In addition, this gene is expressed at much higher levels in fetal lung (CT=30) when compared to expression in the adult counterpart (CT=34). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[0641] Panel 4.1D Summary: Ag4461 Two experiments with the same probe and primer set produce results that are in reasonable agreement, with highest expression in resting neutrophils and kidney (CTs=31). Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and specificaly between resting and activated neutrophils.

[0642] general oncology screening panel_v—2.4 Summary: Ag4461 Highest expression is seen in kidney cancer (CT=32.5). Low but significant levels of expression are also seen in two samples derived from metastatic melanoma. Thus, modulation of the expression or function of this gene could be effective in the treatment of kidney cancer and metastatic melanoma.

[0643] C. CG112776-01: Gag-like

[0644] Expression of gene CG112776-01 was assessed using the primer-probe set Ag4462, described in Table CA. Results of the RTQ-PCR runs are shown in Tables CB, CC, CD and CE.

TABLE CA
Probe Name Ag4462
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gggttgaggaagactaggagaa-3′	22	1021	95
Probe	TET-5′-actcaatgctatccaccattacccag-3′-TAMRA	26	1055	96
Reverse	5′-ctgagggattttcttcttttcc-3′	22	1081	97

[0645]

TABLE CB
CNS neurodegeneration v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4462,		Ag4462,
Tissue Name	Run 224621597	Tissue Name	Run 224621597
AD 1 Hippo	5.1	Control (Path) 3	14.0
		Temporal Ctx
AD 2 Hippo	39.5	Control (Path) 4	24.7
		Temporal Ctx
AD 3 Hippo	17.0	AD 1 Occipital Ctx	29.9
AD 4 Hippo	18.6	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	60.7	AD 3 Occipital Ctx	8.3
AD 6 Hippo	12.2	AD 4 Occipital Ctx	20.4
Control 2 Hippo	9.9	AD 5 Occipital Ctx	28.1
Control 4 Hippo	9.9	AD 6 Occipital Ctx	22.4
Control (Path) 3	23.0	Control 1 Occipital	9.0
Hippo		Ctx
AD 1 Temporal Ctx	45.1	Control 2 Occipital	55.9
		Ctx
AD 2 Temporal Ctx	76.3	Control 3 Occipital	39.8
		Ctx
AD 3 Temporal Ctx	12.2	Control 4 Occipital	12.1
		Ctx
AD 4 Temporal Ctx	47.3	Control (Path) 1	92.0
		Occipital Ctx
AD 5 Inf Temporal	66.0	Control (Path) 2	28.1
Ctx		Occipital Ctx
AD 5 Sup Temporal	39.2	Control (Path) 3	4.2
Ctx		Occipital Ctx
AD 6 Inf Temporal	92.0	Control (Path) 4	35.4
Ctx		Occipital Ctx
AD 6 Sup Temporal	100.0	Control 1 Parietal	8.6
Ctx		Ctx
Control 1 Temporal	7.7	Control 2 Parietal	27.2
Ctx		Ctx
Control 2 Temporal	27.0	Control 3 Parietal	40.6
Ctx		Ctx
Control 3 Temporal	27.0	Control (Path) 1	38.7
Ctx		Parietal Ctx
Control 3 Temporal	6.5	Control (Path) 2	29.9
Ctx		Parietal Ctx
Control (Path) 1	56.3	Control (Path) 3	13.7
Temporal Ctx		Parietal Ctx
Control (Path) 2	50.7	Control (Path) 4	41.2
Temporal Ctx		Parietal Ctx

[0646]

TABLE CC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4462,		Ag4462,
Tissue Name	Run 222566753	Tissue Name	Run 222566753
Adipose	3.3	Renal ca. TK-10	2.0
Melanoma*	33.0	Bladder	6.0
Hs688(A).T
Melanoma*	27.2	Gastric ca. (liver met.) NCI-N87	54.7
Hs688(B).T
Melanoma* MM	1.6	Gastric ca. KATO III	19.9
Melanoma*	5.1	Colon ca. SW-948	0.9
LOXIMVI
Melanoma*	1.0	Colon ca. SW480	3.6
SK-MEL-5
Squamous cell	3.1	Colon ca.* (SW480 met)	0.6
carcinoma SCC-4		SW620
Testis Pool	8.4	Colon ca. HT29	0.3
Prostate ca.* (bone	14.4	Colon ca. HCT-116	0.2
met) PC-3
Prostate Pool	8.0	Colon ca. CaCo-2	16.3
Placenta	1.7	Colon cancer tissue	3.9
Uterus Pool	5.2	Colon ca. SW1116	0.5
Ovarian ca. OVCAR-3	1.9	Colon ca. Colo-205	1.5
Ovarian ca. SK-OV-3	16.4	Colon ca. SW-48	0.8
Ovarian ca. OVCAR-4	5.6	Colon Pool	30.1
Ovarian ca. OVCAR-5	32.3	Small Intestine Pool	16.3
Ovarian ca. IGROV-1	2.9	Stomach Pool	7.5
Ovarian ca. OVCAR-	6.4	Bone Marrow Pool	27.9
8
Ovary	10.7	Fetal Heart	4.5
Breast ca. MCF-7	1.6	Heart Pool	8.1
Breast ca MDA-MB-	29.3	Lymph Node Pool	35.6
231
Breast ca. BT 549	4.7	Fetal Skeletal Muscle	6.1
Breast ca. T47D	26.2	Skeletal Muscle Pool	5.2
Breast ca. MDA-N	6.0	Spleen Pool	2.2
Breast Pool	35.6	Thymus Pool	13.9
Trachea	14.6	CNS cancer (glio/astro)	5.8
		U87-MG
Lung	7.7	CNS cancer (glio/astro)	100.0
		U-118-MG
Fetal Lung	21.8	CNS cancer (neuro: met)	1.9
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-589	23.8
Lung ca. LX-1	2.9	CMS cancer (astro) SNB-75	91.4
Lung ca. NCI-H146	0.2	CNS cancer (glio) SNB-	3.7
		19
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-	33.7
		295
Lung ca. A549	16.7	Brain (Amygdala) Pool	0.8
Lung ca. NCI-H526	0.5	Brain (cerebellum)	1.5
Lung ca. NCI-H23	14.4	Brain (fetal)	9.6
Lung ca. NCI-H460	27.2	Brain (Hippocampus) Pool	2.6
Lung ca. HOP-62	10.7	Cerebral Cortex Pool	2.1
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	1.7
Liver	0.5	Brain (Thalamus) Pool	2.8
Fetal Liver	1.0	Brain (whole)	2.0
Liver ca. HepG2	0.0	Spinal Cord Pool	2.0
Kidney Pool	25.9	Adrenal Gland	2.9
Fetal Kidney	53.2	Pituitary gland Pool	1.2
Renal ca. 786-0	4.5	Salivary Gland	2.0
Renal ca. A498	4.0	Thyroid (female)	1.8
Renal ca. ACHN	22.4	Pancreatic ca. CAPAN2	23.0
Renal ca. UO-31	16.8	Pancreas Pool	34.2

[0647]

TABLE CD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4462,		Ag4462,
Tissue Name	Run 44579105	Tissue Name	Run 44579105
Secondary Th1 act	16.0	HUVEC IL-1beta	32.3
Secondary Th2 act	3.5	HUVEC IFN gamma	27.5
Secondary Tr1 act	10.9	HUVEC TNF alpha + IFN	26.6
		gamma
Secondary Th1 rest	1.6	HUVEC TNF alpha + IL4	69.7
Secondary Th2 rest	0.3	HUVEC IL-11	25.2
Secondary Tr1 rest	0.8	Lung Microvascular EC	100.0
		none
Primary Th1 act	5.2	Lung Microvascular EC	97.3
		TNFalpha + IL-1beta
Primary Th2 act	1.1	Microvascular Dermal EC	43.8
		none
Primary Tr1 act	6.1	Microsvasular Dermal EC	53.6
		TNFalpha + IL-1beta
Primary Th1 rest	2.5	Bronchial epithelium	7.9
		TNFalpha + IL-1beta
Primary Th2 rest	0.0	Small airway epithelium	5.5
Primary Tr1 rest	0.0	Small airway epithelium	10.2
		TNFalpha + IL-1beta
CD45RA CD4	3.2	Coronery artery SMC rest	19.6
lymphocyte act
CD45RO CD4	0.0	Coronery artery SMC	13.7
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	28.1
Secondary CD8	0.0	Astrocytes TNFalpha + IL-	17.6
lymphocyte rest		1beta
Secondary CD8	0.5	KU-812 (Basophil) rest	0.0
lymphocyte act
CD4 lymphocyte none	2.4	KU-812 (Basophil)	0.7
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	31.4
CD95 CH11		none
LAK cells rest	0.9	CCD1106 (Keratinocytes)	9.0
		TNFalpha + IL-1 beta
LAK cells IL-2	1.7	Liver cirrhosis	3.7
LAK cells IL-2 + IL-12	1.8	NCI-H292 none	9.7
LAK cells IL-2 + IFN	3.1	NCI-H292 IL-4	5.4
gamma
LAK cells IL-2 + IL-18	2.6	NCI-H292 IL-9	13.8
LAK cells	0.9	NCI-H292 1L-13	9.9
PMA/ionomycin
NK Cells IL-2 rest	6.0	NCI-H292 IFN gamma	11.2
Two Way MLR 3 day	7.0	HPAEC none	39.0
Two Way MLR 5 day	0.8	HPAEC TNFalpha + IL-1	70.7
		beta
Two Way MLR 7 day	2.4	Lung fibroblast none	25.2
PBMC rest	2.8	Lung fibroblast TNFalpha +	2.0
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	16.4
PBMC PHA-L	0.0	Lung fibroblast IL-9	44.4
Ramos (B cell) none	0.0	Lung fibroblast IL-13	46.0
Ramos (B cell)	0.0	Lung fibroblast IFN gamma	6.5
ionomycin
B lymphocytes PWM	0.8	Dermal fibroblast CCD1070	25.0
		rest
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070	6.5
and IL-4		TNFalpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	4.0
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN	3.0
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	13.5
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	6.4
Dendritic cells anti-	0.8	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.8
Monocytes LPS	0.7	Colon	1.5
Macrophages rest	0.0	Lung	3.8
Macrophages LPS	0.0	Thymus	11.2
HUVEC none	29.1	Kidney	15.2
HUVEC starved	48.3

[0648]

TABLE CE
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4462,		Ag4462,
Tissue Name	Run 268672046	Tissue Name	Run 268672046
Colon cancer 1	11.1	Bladder cancer NAT 2	0.4
Colon cancer NAT 1	2.9	Bladder cancer NAT 3	0.3
Colon cancer 2	3.3	Bladder cancer NAT 4	24.0
Colon cancer NAT 2	1.8	Prostate adenocarcinoma 1	39.2
Colon cancer 3	25.9	Prostate adenocarcinoma 2	2.8
Colon cancer NAT 3	10.4	Prostate adenocarcinoma 3	16.5
Colon malignant cancer 4	4.6	Prostate adenocarcinoma 4	6.3
Colon normal adjacent tissue 4	1.9	Prostate cancer NAT 5	5.6
Lung cancer 1	18.7	Prostate adenocarcinoma 6	5.3
Lung NAT 1	1.6	Prostate adenocarcinoma 7	5.9
Lung cancer 2	56.6	Prostate adenocarcinoma 8	2.5
Lung NAT 2	1.8	Prostate adenocarcinoma 9	16.5
Squamous cell carcinoma 3	12.0	Prostate cancer NAT 10	3.5
Lung NAT 3	0.5	Kidney cancer 1	42.3
metastatic melanoma 1	13.4	Kidney NAT 1	9.1
Melanoma 2	0.6	Kidney cancer 2	71.7
Mclanoma 3	0.3	Kidney NAT 2	13.5
metastatic melanoma 4	46.7	Kidney cancer 3	37.1
metastatic melanoma 5	100.0	Kidney NAT 3	3.1
Bladder cancer 1	4.1	Kidney cancer 4	7.1
Bladder cancer NAT 1	0.0	Kidney NAT 4	1.3
Bladder cancer 2	3.6

[0649] CNS_neurodegeneration_v1.0 Summary: Ag4462 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene is found to be upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0650] General_screening_panel_v1.4 Summary: Ag4462 Highest expression of this gene is seen in a brain cancer cell line (CT=29.5). This gene is widely expressed in this panel, with moderate to low expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0651] Among tissues with metabolic function, this gene is expressed at moderate to low levels in adipose, adrenal gland, pancreas, and adult and fetal skeletal muscle and heart. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0652] This gene is also expressed at low but significant levels in the CNS, including the hippocampus and thalamus. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurological disorders.

[0653] Panel 4.1D Summary: Ag4462 This transcript is expressed at higher levels in endothelial cells, with highest expression seen in untreated lung microvascular EC (CT=31). Expression is also seen in samples derived from HPAEC, HUVEC and lung microvascular EC, as well as lung and dermal fibroblasts. Therapies designed with the protein encoded by this transcript could be important in regulating endothelium function including leukocyte extravasation, a major component of inflammation during asthma, IBD, and psoriasis.

[0654] general oncology screening panel_v—2.4 Summary: Ag4462 This gene is widely expressed in this panel, with highest expression in a sample derived from metastatic melanoma (CT=31.2). In addition, this gene is more highly expressed in lung and kidney 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 kidney cancer.

[0655] D. CG122759-01: Guanine Nucleotide Exchange Factor

[0656] Expression of gene CG122759-01 was assessed using the primer-probe set Ag4535, described in Table DA. Results of the RTQ-PCR runs are shown in Tables DB and DC.

TABLE DA
Probe Name Ag4535
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aacgggcacattaactttaagc-3′	22	1057	98
Probe	TET-5′-ttctgggagatctccagacagatcca-3′-TAMRA	26	1084	99
Reverse	5′-ctgtgtccatgtcatgaactca-3′	22	1110	100

[0657]

TABLE DB
CNS neurodegeneration v1.0
	Rel. Exp.		Rel. Exp.
	(%)		(%)
	Ag4535,		Ag4535,
	Run		Run
Tissue Name	224702761	Tissue Name	224702761
AD 1 Hippo	11.8	Control (Path) 3	7.5
		Temporal Ctx
AD 2 Hippo	14.1	Control (Path) 4	31.2
		Temporal Ctx
AD 3 Hippo	7.9	AD 1 Occipital Ctx	10.4
AD 4 Hippo	5.0	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	97.3	AD 3 Occipital Ctx	4.2
AD 6 Hippo	55.1	AD 4 Occipital Ctx	12.1
Control 2 Hippo	37.1	AD 5 Occipital Ctx	20.4
Control 4 Hippo	7.9	AD 6 Occipital Ctx	49.3
Control (Path) 3	9.5	Control 1 Occipital	0.0
Hippo		Ctx
AD 1 Temporal Ctx	10.2	Control 2 Occipital	50.3
		Ctx
AD 2 Temporal Ctx	19.2	Control 3 Occipital	10.4
		Ctx
AD 3 Temporal Ctx	3.4	Control 4 Occipital	0.0
		Ctx
AD 4 Temporal Ctx	18.0	Control (Path) 1	100.0
		Occipital Ctx
AD 5 Inf Temporal	92.0	Control (Path) 2	6.4
Ctx		Occipital Ctx
AD 5 Sup Temporal	27.9	Control (Path) 3	2.6
Ctx		Occipital Ctx
AD 6 Inf Temporal	35.4	Control (Path) 4	5.9
Ctx		Occipital Ctx
AD 6 Sup Temporal	47.3	Control 1 Parietal	6.1
Ctx		Ctx
Control 1 Temporal	2.4	Control 2 Parietal	38.4
Ctx		Ctx
Control 2 Temporal	39.0	Control 3 Parietal	11.0
Ctx		Ctx
Control 3 Temporal	12.5	Control (Path) 1	76.8
Ctx		Parietal Ctx
Control 4 Temporal	6.9	Control (Path) 2	8.8
Ctx		Parietal Ctx
Control (Path) 1	42.6	Control (Path) 3	0.0
Temporal Ctx		Parietal Ctx
Control (Path) 2	39.2	Control (Path) 4	50.3
Temporal Ctx		Parietal Ctx

[0658]

TABLE DC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4535,		Ag4535,
Tissue Name	Run 222735447	Tissue Name	Run 222735447
Adipose	0.0	Renal ca. TK-10	6.9
Melanoma*	0.0	Bladder	6.0
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*	0.0	Colon ca. SW-948	0.0
LOXIMVI
Melanoma* SK-	25.2	Colon ca. SW480	0.0
MEL-5
Squamous cell	0.0	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	0.0	Colon ca. HT29	0.0
Prostate ca.* (bone	0.0	Colon ca. HCT-116	46.7
met) PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	5.0
Placenta	5.2	Colon cancer tissue	0.0
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	10.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	13.5	Colon Pool	0.0
Ovarian ca. OVCAR-5	13.6	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	33.2	Stomach Pool	0.0
Ovarian ca. OVCAR-	0.0	Bone Marrow Pool	0.0
8
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	2.6
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	4.8
Breast Pool	0.0	Thymus Pool	0.0
Trachea	2.4	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	0.0	CNS cancer (neuro: met)	0.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-	0.0
		539
Lung ca. LX-1	9.3	CNS cancer (astro)	5.0
		SNB-75
Lung ca. NCI-H146	6.7	CNS cancer (glio) SNB-	18.9
		19
Lung ca. SHP-77	11.9	CNS cancer (glio) SF-	0.0
		295
Lung ca. A549	3.3	Brain (Amygdala) Pool	22.2
Lung ca. NCI-H526	0.0	Brain (cerebellum)	71.7
Lung ca. NCI-H23	55.1	Brain (fetal)	27.2
Lung ca. NCI-H460	3.6	Brain (Hippocampus) Pool	18.4
Lung ca. HOP-62	0.0	Cerebial Cortex Pool	34.6
Lung ca. NCI-H522	5.0	Brain (Substantia nigra)	19.1
		Pool
Liver	0.0	Brain (Thalamus) Pool	34.9
Fetal Liver	0.0	Brain (whole)	54.7
Liver ca. HepG2	8.1	Spinal Cord Pool	11.8
Kidney Pool	2.4	Adrenal Gland	2.2
Fetal Kidney	0.0	Pituitary gland Pool	3.2
Renal ca. 786-0	0.0	Salivary Gland	2.7
Renal ca. A498	100.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	10.7
Renal ca. UO-31	0.0	Pancreas Pool	5.0

[0659] CNS_neurodegeneration_v1.0 Summary: Ag4535 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. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0660] General_screening_panel_v1.4 Summary: Ag4535 Expression of this gene is restricted to a sample derived from a kidney cancer cell line and the cerebellum(CTs=34-35). Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of kidney cancer.

[0661] Panel 4.1D Summary: Ag4535 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0662] E. CG122759-02: Guanine Nucleotide Exchange Factor

[0663] Expression of gene full length physical clone CG122759-02, a variant of CG1227598-01 above, was assessed using the primer-probe set Ag6816, described in Table EA. Results of the RTQ-PCR runs are shown in Tables EB and EC.

TABLE EA
Probe Name Ag6816
Primers	Sequences	Length	Start Position	SEQ ID No
Forward	5′-tgccgggtggtgaaga-3′	16	688	101
Probe	TET-5′-actccaacatgcgggcccggt-3′-TAMRA	21	710	102
Reverse	5′-actcccgggccacatc-3′	16	739	103

[0664]

TABLE EB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6816,		Ag6816,
	Run		Run
Tissue Name	278022737	Tissue Name	278022737
AD 1 Hippo	11.8	Control (Path) 3	2.8
		Temporal Ctx
AD 2 Hippo	19.5	Control (Path) 4	35.6
		Temporal Ctx
AD 3 Hippo	17.8	AD 1 Occipital Ctx	6.1
AD 4 Hippo	3.5	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	100.0	AD 3 Occipital Ctx	3.0
AD 6 Hippo	50.0	AD 4 Occipital Ctx	12.2
Control 2 Hippo	55.1	AD 5 Occipital Ctx	13.4
Control 4 Hippo	8.8	AD 6 Occipital Ctx	38.2
Control (Path) 3	3.6	Control 1 Occipital	0.5
Hippo		Ctx
AD 1 Temporal Ctx	14.1	Control 2 Occipital	87.7
		Ctx
AD 2 Temporal Ctx	17.1	Control 3 Occipital	15.2
		Ctx
AD 3 Temporal Ctx	6.0	Control 4 Occipital	1.7
		Ctx
AD 4 Temporal Ctx	12.6	Control (Path) 1	84.7
		Occipital Ctx
AD 5 Inf Temporal	62.0	Control (Path) 2	1.7
Ctx		Occipital Ctx
AD 5 SupTemporal	45.1	Control (Path) 3	0.8
Ctx		Occipital Ctx
AD 6 Inf Temporal	43.2	Control (Path) 4	4.9
Ctx		Occipital Ctx
AD 6 Sup Temporal	26.2	Control 1 Parietal	2.5
Ctx		Ctx
Control 1 Temporal	0.6	Control 2 Parietal	26.4
Ctx		Ctx
Control 2 Temporal	47.6	Control 3 Parietal	10.7
Ctx		Ctx
Control 3 Temporal	13.7	Control (Path) 1	70.7
Ctx		Parietal Ctx
Control 4 Temporal	2.6	Control (Path) 2	18.6
Ctx		Parietal Ctx
Control (Path) 1	62.4	Control (Path) 3	1.7
Temporal Ctx		Parietal Ctx
Control (Path) 2	45.1	Control (Path) 4	18.2
Temporal Ctx		Parietal Ctx

[0665]

TABLE EC
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6816,		Ag6816,
	Run		Run
Tissue Name	278022639	Tissue Name	278022639
Secondary Th1 act	5.4	HUVEC IL-1beta	1.8
Secondary Th2 act	4.2	HUVEC IFN gamma	0.0
Sccondary Tr1 act	1.8	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	14.1	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	10.0	Lung Microvascular EC	0.0
		none
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNFalpha + IL-1beta
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	2.0	Bronchial epithelium	23.0
		TNFalpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	70.7
		none
Primary Tr1 rest	0.0	Small airway epithelium	100.0
		TNFalpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC rest	0.0
lymphocyte act
CD45RO CD4	5.0	Coronery artery SMC	0.0
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	4.1	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNFalpha + 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-	7.5	CCD1106 (Keratinocytes)	70.2
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	28.9
		TNFalpha + IL-1beta
LAK cells IL-2	12.9	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	40.1	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 +	0.0
		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 gamma	3.3
ionomycin
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070 rest	0.0
B lymphocytes CD40L	0.0	Dermal fibroblast CCD1070 TNF alpha	81.2
and IL-4
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 IL-1 beta	0.0
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN	0.0
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	6.5
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	18.6
Monocytes LPS	0.0	Colon	0.0
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	1.8	Thymus	0.0
HUVEC none	0.0	Kidney	21.8
HUVEC starved	0.0

[0666] CNS_neurodegeneration_v1.0 Summary: Ag6816 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. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0667] Panel 4.1D Summary: Ag6816 Expression of this gene is limited to activated and untreated small airway epithelium, untreated kertainocytes, and TNF alpha treated dermal fibroblasts (CTs=34-35). Thus, expression of this gene could be used to differentiate these samples from the other samples on this panel.

[0668] F. CG124599-01: MAXP1

[0669] Expression of gene CG124599-01 was assessed using the primer-probe sets Ag4671 and Ag4674, described in Tables FA and FB. Results of the RTQ-PCR runs are shown in Tables FC, FD, FE and FF.

TABLE FA
Probe Name Ag4671
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aggtagagtgggatgccttct-3′	21	1096	104
Probe	TET-5′-ccatccctgaacttcagaacttcctaaca-3′-TAMRA	29	1117	105
Reverse	5′-gattttgtcctgctcctctttt-3′	22	1154	106

[0670]

TABLE FB
Probe Name Ag4674
Primers	Sequences	Length	Start Position	SEQ ID No
Forward	5′-gctcttccagaaactctccatt-3′	22	989	107
Probe	TET-5′-ctctacctgcgcctgcttgctgg-3′-TAMRA	23	1023	108
Reverse	5′-tcattctcctttagcacaaagc-3′	22	1066	109

[0671]

TABLE FC
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4671,		Ag4671,
	Run		Run
Tissue Name	224702763	Tissue Name	224702763
AD 1 Hippo	14.1	Control (Path) 3	4.5
		Temporal Ctx
AD 2 Hippo	26.8	Control (Path) 4	32.3
		Temporal Ctx
AD 3 Hippo	7.7	AD 1 Occipital Ctx	22.7
AD 4 Hippo	4.2	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	100.0	AD 3 Occipital Ctx	6.2
AD 6 Hippo	57.8	AD 4 Occipital Ctx	13.4
Control 2 Hippo	26.4	AD 5 Occipital Ctx	35.6
Control 4 Hippo	8.9	AD 6 Occipital Ctx	36.9
Control (Path) 3	4.3	Control 1 Occipital	7.5
Hippo		Ctx
AD 1 Temporal Ctx	15.3	Control 2 Occipital	51.1
		Ctx
AD 2 Temporal Ctx	19.3	Control 3 Occipital	19.5
		Ctx
AD 3 Temporal Ctx	8.8	Control 4 Occipital	4.8
		Ctx
AD 4 Temporal Ctx	9.7	Control (Path) 1	77.9
		Occipital Ctx
AD 5 Inf Temporal	73.7	Control (Path) 2	15.0
Ctx		Occipital Ctx
AD 5 SupTemporal	36.6	Control (Path) 3	1.5
Ctx		Occipital Ctx
AD 6 Inf Temporal	53.6	Control (Path) 4	21.0
Ctx		Occipital Ctx
AD 6 Sup Temporal	45.7	Control 1 Parietal	6.5
Ctx		Ctx
Control 1 Temporal	7.2	Control 2 Parietal	30.8
Ctx		Ctx
Control 2 Temporal	32.1	Control 3 Parietal	31.9
Ctx		Ctx
Control 3 Temporal	13.0	Control (Path) 1	75.8
Ctx		Parietal Ctx
Control 4 Temporal	5.6	Control (Path) 2	31.2
Ctx		Parietal Ctx
Control (Path) 1	65.5	Control (Path) 3	2.2
Temporal Ctx		Parietal Ctx
Control (Path) 2	40.3	Control (Path) 4	52.9
Temporal Ctx		Parietal Ctx

[0672]

TABLE FD
General_screening_panel_v1.4
	Rel. Exp. (%)	Rel. Exp. (%)		Rel. Exp. (%)	Rel. Exp. (%)
	Ag4671, Run	Ag4674, Run		Ag4671, Run	Ag4674, Run
Tissue Name	222811513	222811526	Tissue Name	222811513	222811526
Adipose	17.1	6.6	Renal ca. TK-10	7.9	5.0
Melanoma*	5.0	5.3	Bladder	43.5	26.1
Hs688(A).T
Melanoma*	6.9	7.0	Gastric ca. (liver	100.0	100.0
Hs688(B).T			met.) NCI-N87
Melanoma*	1.5	0.8	Gastric ca. KATO	22.4	26.1
M14			III
Melanoma*	1.4	1.1	Colon ca. SW-948	7.1	5.4
LOXIMVI
Melanoma*	4.7	2.9	Colon ca. SW480	23.3	21.9
SK-MEL-5
Squamous cell	9.4	8.2	Colon ca.*	6.3	4.7
carcinoma			(SW480 met)
SCC-4			SW620
Testis Pool	5.6	1.9	Colon ca. HT29	9.7	8.0
Prostate ca.*	21.9	18.7	Colon ca. HCT-	12.3	8.9
(bone met)			116
PC-3
Prostate Pool	7.2	3.8	Colon ca. CaCo-2	2.3	1.0
Placenta	3.0	4.6	Colon cancer	16.4	11.5
			tissue
Uterus Pool	4.9	2.2	Colon ca.	2.4	1.7
			SW1116
Ovarian ca.	0.8	0.6	Colon ca. Colo-205	15.9	13.2
OVCAR-3
Ovarian ca.	3.0	2.4	Colon ca. SW-48	0.4	0.3
SK-OV-3
Ovarian ca	3.2	2.1	Colon Pool	11.1	6.3
OVCAR-4
Ovarian ca.	26.4	18.4	Small Intestine	5.6	3.7
OVCAR-5			Pool
Ovarian ca	1.8	0.5	Stomach Pool	5.8	4.7
IGROV-1
Ovarian ca.	1.0	1.7	Bone Marrow	9.5	0.9
OVCAR-8			Pool
Ovary	8.1	6.2	Fetal Heart	2.6	1.8
Breast ca.	2.5	2.1	Heart Pool	3.2	2.3
MCF-7
Breast ca.	8.8	7.7	Lymph Node Pool	11.7	8.2
MDA-MB-231
Breast ca. BT	0.5	0.3	Fetal Skeletal	2.3	2.3
549			Muscle
Breast ca.	49.0	33.7	Skeletal Muscle	8.6	5.4
T47D			Pool
Breast ca	0.5	0.4	Spleen Pool	62.9	45.7
MDA-N
Breast Pool	9.8	6.9	Thymus Pool	44.8	28.9
Trachea	40.1	32.5	CNS cancer	4.2	3.6
			(glio/astro) U87-
			MG
Lung	1.6	0.3	CNS cancer	3.1	2.8
			(glio/astro) U-
			118-MG
Fetal Lung	32.8	21.2	CNS cancer	1.6	1.2
			(neuro:met) SK-N-AS
Lung ca. NCI-N417	0.1	0.0	CNS cancer	13.3	12.0
			(astro) SF-539
Lung ca. LX-1	6.3	7.0	CNS cancer	2.9	1.2
			(astro) SNB-75
Lung ca. NCI-	4.9	3.2	CNS cancer (glio)	0.9	0.7
H146			SNB-19
Lung ca. SHP-77	37.9	32.1	CNS cancer (glio)	13.8	11.3
			SF-295
Lung ca. A549	9.7	9.7	Brain (Amygdala)	9.7	8.8
			Pool
Lung ca. NCI-	5.8	4.7	Brain	11.0	7.2
H526			(cerebellum)
Lung ca. NCI-	3.9	2.9	Brain (fetal)	5.2	3.3
H23
Lung ca. NCI-	1.1	0.8	Brain	10.7	10.3
H460			(Hippocampus)
			Pool
Lung ca. HOP-	7.6	11.7	Cerebral Cortex	19.8	11.0
62			Pool
Lung ca. NCI-	1.7	1.4	Brain (Substantia	9.8	11.4
H522			nigra) Pool
Liver	5.4	3.7	Brain (Thalamus)	22.8	29.3
			Pool
Fetal Liver	14.6	12.3	Brain (whole)	23.7	15.5
Liver ca.	0.9	0.8	Spinal Cord Pool	6.3	4.5
HepG2
Kidney Pool	14.0	11.7	Adrenal Gland	26.6	24.8
Fetal Kidney	3.1	3.1	Pituitary gland	5.9	4.2
			Pool
Renal ca. 786-	9.5	8.7	Salivary Gland	31.9	33.2
0
Renal ca.	2.9	1.5	Thyroid (female)	7.5	5.3
A498
Renal ca.	0.5	0.5	Pancreatic ca.	62.4	55.1
ACHN			CAPAN2
Renal ca. UO-	0.3	0.2	Pancreas Pool	15.4	9.4
31

[0673]

TABLE FE
Oncology_cell_line_screening_panel_v3.1
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4674,		Ag4674,
	Run		Run
Tissue Name	224053017	Tissue Name	224053017
Daoy	1.0	Ca Ski_Cervical epidermoid	6.8
Medulloblastoma/Cerebellum		carcinoma (metastasis)
TE671	7.9	ES-2_Ovarian clear cell	0.1
Medulloblastom/Cerebellum		carcinoma
D283 Med	0.5	Ramos/6h stim_Stimulated with	6.3
Medulloblastoma/Cerebellum		PMA/ionomycin 6h
PFSK-1 Primitive	1.6	Ramos/14h stim_Stimulated with	7.3
Neuroectodermal/Cerebellum		PMA/ionomycin 14h
XF-498_CNS	0.3	MEG-01_Chronic myelogenous	12.8
		leukemia (megokaryoblast)
SNB-78_CNS/glioma	0.8	Raji_Burkitt's lymphoma	5.0
SF-268_CNS/glioblastoma	0.3	Daudi_Burkitt's lymphoma	11.0
T98G_Glioblastoma	2.3	U266_B-cell	42.6
		plasmacytoma/myeloma
SK-N-SH_Neuroblastoma	1.5	CA46_Burkitt's lymphoma	5.7
(metastasis)
SF-295_CNS/glioblastoma	2.5	RL_non-Hodgkin's B-cell	6.2
		lymphoma
Cerebellum	3.0	JM1_pre-B-cell	8.2
		lymphoma/leukemia
Cerebellum	1.6	Jurkat_T cell leukemia	30.4
NCI-H292_Mucoepidermoid	17.3	TF-1_Erythroleukemia	25.0
lung ca.
DMS-114_Small cell lung	0.4	HUT 78_T-cell lymphoma	100.0
cancer
DMS-79_Small cell lung	3.3	U937_Histiocytic lymphoma	17.9
cancer/neuroendocrine
NCI-H146_Small cell lung	2.9	KU-812_Myelogenous leukemia	10.7
cancer/neuroendocrine
NCI-H526_Small cell lung	5.5	769-P_Clear cell renal ca.	0.3
cancer/neuroendocrine
NCI-N417_Small cell lung	0.0	Caki-2_Clear cell renal ca	0.1
cancer/neuroendocrine
NCI-H82_Small cell lung	0.7	SW 839_Clear cell renal ca.	0.5
cancer/neuroendocrine
NCI-H157_Squamous cell lung	0.2	G401_Wilms' tumor	0.2
cancer (metastasis)
NCI-H1155_Large cell lung	3.7	Hs766T_Pancreatic ca. (LN	1.7
cancer/neuroendocrine		metastasis)
NCI-H1299_Large cell lung	1.1	CAPAN-1_Pancreatic	2.8
cancer/neuroendocrine		adenocarcinoma (liver metastasis)
NCI-H727_Lung carcinoid	5.1	SU86.86_Pancreatic carcinoma	5.0
		(liver metastasis)
NCI-UMC-11_Lung carcinoid	17.4	BxPC-3_Pancreatic	2.8
		adenocarcinoma
LX-1_Small cell lung cancer	2.4	HPAC Pancreatic	7.5
		adenocarcinoma
Colo-205_Colon cancer	8.7	MIA PaCa-2_Pancreatic ca.	0.0
KM12_Colon cancer	0.1	CFPAC-1_Pancreatic ductal	12.8
		adenocarcinoma
KM20L2_Colon cancer	0.5	PANC-1_Pancreatic epithelioid	0.2
		ductal ca.
NCI-H716_Colon cancer	1.5	T24_Bladder ca. (transitional cell)	0.0
SW-48_Colon adenocarcinoma	0.0	5637_Bladder ca.	0.8
SW1116_Colon	0.8	HT-1197_Bladder ca.	0.5
adenocarcinoma
LS 174T_Colon	0.0	UM-UC-3_Bladder ca.	0.0
adenocarcinoma		(transitional cell)
SW-948_Colon adenocarcinoma	1.9	A204_Rhabdomyosarcoma	0.1
SW-480_Colon adenocarcinoma	0.7	HT-1080_Fibrosarcoma	2.7
NCI-SNU-5_Gastric ca.	3.3	MG-63_Osteosarcoma (bone)	0.8
KATO III_Stomach	2.8	SK-LMS-1_Leiomyosarcoma	2.3
		(vulva)
NCI-SNU-16_Gastric ca.	1.6	SJRH30_Rhabdomyosarcoma	1.4
		(met to bone marrow)
NCI-SNU-1_Gastric ca.	0.0	A431_Epidermoid ca.	6.1
RF-1_Gastric adenocarcinoma	14.7	WM266-4_Melanoma	0.3
RF-48_Gastric adenocarcinoma	17.7	DU 145_Prostate	2.6
MKN-45_Gastric ca.	0.8	MDA-MB-468_Breast	2.6
		adenocarcinoma
NCI-N87_Gastric ca.	8.5	SSC-4_Tongue	2.0
OVCAR-5_Ovarian ca.	0.8	SSC-9_Tongue	1.6
RL95-2_Uterine carcinoma	0.1	SSC-15_Tongue	4.9
HelaS3_Cervical	4.1	CAL 27_Squamous cell ca. of	4.0
adenocarcinoma		tongue

[0674]

TABLE FF
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4671,		Ag4671,
	Run		Run
Tissue Name	200755347	Tissue Name	200755347
Secondary Th1 act	85.9	HUVEC IL-1beta	0.2
Secondary Th2 act	97.9	HUVEC IFN gamma	0.7
Secondary Tr1 act	98.6	HUVEC TNF alpha + IFN gamma	1.0
Secondary Th1 rest	23.8	HUVEC TNF alpha + IL4	0.1
Secondary Th2 rest	27.5	HUVEC IL-11	0.1
Secondary Tr1 rest	65.1	Lung Microvascular EC	0.4
		none
Primary Th1 act	50.7	Lung Microvascular EC	2.4
		TNFalpha + IL-1beta
Primary Th2 act	81.2	Microvascular Dermal EC	0.3
		none
Primary Tr1 act	79.6	Microsvasular Dermal EC	6.4
		TNFalpha + IL-1beta
Primary Th1 rest	24.5	Bronchial epithelium	2.2
		TNFalpha + IL1beta
Primary Th2 rest	15.6	Small airway epithelium	0.7
		none
Primary Tr1 rest	33.9	Small airway epithelium	0.9
		TNFalpha + IL-1beta
CD45RA CD4	33.0	Coronery artery SMC rest	0.7
lymphocyte act
CD45RO CD4	100.0	Coronery artery SMC	0.6
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	57.4	Astrocytes rest	0.2
Secondary CD8	70.7	Astrocytes TNFalpha + IL-	4.6
lymphocyte rest		1beta
Secondary CD8	43.5	KU-812 (Basophil) rest	6.4
lymphocyte act
CD4 lymphocyte none	26.4	KU-812 (Basophil)	16.5
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	44.8	CCD1106 (Keratinocytes)	0.3
CD95 CH11		none
LAK cells rest	49.0	CCD1106 (Keratinocytes)	0.5
		TNFalpha + IL-1beta
LAK cells IL-2	47.3	Liver cirrhosis	2.9
LAK cells IL-2 + IL-12	23.8	NCI-H292 none	7.8
LAK cells IL-2 + IFN	24.5	NCI-H292 IL-4	8.4
gamma
LAK cells IL-2 + IL-18	30.4	NCI-H292 IL-9	10.2
LAK cells	86.5	NCI-H292 IL-13	10.9
PMA/ionomycin
NK Cells IL-2 rest	73.7	NCI-H292 IFN gamma	6.2
Two Way MLR 3 day	36.9	HPAEC none	0.3
Two Way MLR 5 day	36.6	HPAEC TNF alpha + IL-1	0.7
		beta
Two Way MLR 7 day	37.9	Lung fibroblast none	0.8
PBMC rest	27.7	Lung flbroblast TNF alpha + IL-I beta	1.0
PBMC PWM	43.8	Lung fibroblast IL-4	0.4
PBMC PHA-L	49.0	Lung fibroblast IL-9	1.1
Ramos (B cell) none	3.3	Lung fibroblast IL-13	1.2
Ramos (B cell)	5.8	Lung fibroblast IFN gamma	2.0
ionomycin
B lymphocytes PWM	29.1	Dermal fibroblast CCD1070	2.6
		rest
B lymphocytcs CD40L	26.8	Dermal fibrohlast CCD1070	42.6
and IL-4		TNF alpha
EOL-1 dbcAMP	21.0	Dermal fibroblast CCD1070	0.4
		IL-1 beta
EOL-1 dbcAMP	78.5	Dermal fibroblast IFN	3.5
PMA/ionomycin		gamma
Dendritic cells none	10.7	Dermal fibroblast IL-4	4.9
Dendritic cells LPS	7.5	Dermal Fibroblasts rest	6.8
Dendritic cells anti-	15.7	Neutrophils TNFa + LPS	73.7
CD40
Monocytes rest	33.0	Neutrophils rest	54.7
Monocytes LPS	47.3	Colon	3.2
Macrophages rest	21.0	Lung	3.3
Macrophages LPS	18.8	Thymus	35.6
HUVEC none	0.0	Kidney	2.8
HUVEC starved	0.2

[0675] CNS_neurodegeneration_v1.0 Summary: Ag4671 This panel confirms the expression of this gene at moderate levels in the brain in an independent group of individuals. This gene appears to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0676] General_screening_panel_v1.4 Summary: Ag4671/Ag4674 Two experiments with two different probe and primer sets produce results that are in excellent agreement, with highest expression of this gene is seen in a gastric cancer cell line (CTs=28). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0677] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0678] This gene is also expressed at moderate to low levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0679] In addition, this gene is expressed at much higher levels in fetal lungtissue (CTs=30) when compared to expression in the adult counterpart (CTs=34-36). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[0680] Oncology_cell_line_screening_panel_v3.1 Summary: Ag4674 Highest expression of this (gene is seen in a T cell lymphoma cell line (CT=27.3). In addition, moderate to low levels of expression are seen in most of the cell lines on this panel. This expression is in agreement with expression seen in Panel 1.4. Please see Panel 1.4 for discussion of this gene in cancer.

[0681] Panel 4.1D Summary: Ag4671 Highest expression of this gene is seen in activated CD45RO CD4 lymphocytes (CT=27). In addition, this transcript is expressed at high levels in in T cells, particularly chronically activated Th1, Th2 and Tr1 cells. Macrophages, B cells, LAK cells, eosinophils, monocytes and dendritic cells also express the transcript. Thus, this transcript or the protein it encodes could be used to detect hematopoietically-derived cells. Furthermore, therapeutics designed with the protein encoded by this transcript could be important in the regulation of the function of antigen presenting cells (macrophages and dendritic cells) or T cells and be important in the treatment of asthma, emphysema, psoriasis, arthritis, and IBD.

[0682] G. CG125414-01 and CG125414-02: XAF-1 with Zinc Finger Motif

[0683] Expression of gene CG125414-01 and full length physical clone CG125414-02 was assessed using the primer-probe set Ag6580, described in Table GA Results of the RTQ-PCR runs are shown in Tables GB and GC. Please note that CG125414-02 represents a full-length physical clone of the CG125414-01 gene, validating the prediction of the gene sequence.

TABLE GA
Probe Name Ag6580
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tccacgatggagaaagatgt-3′	20	553	110
Probe	TET-5′-tcctcttcattctgaaagttcatcaaa-3′-TAMRA	27	603	111
Reverse	5′-ttttgcttcttggtgctttc-3′	20	630	112

[0684]

TABLE GB
General_screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6580,		Ag6580,
	Run		Run
Tissue Name	277255894	Tissue Name	277255894
Adipose	4.3	Renal ca. TK-10	0.0
Melanoma*	4.3	Bladder	55.9
Hs688 (A).T
Melanoma*	7.4	Gastric ca. (liver met.) NCI-N87	100.0
Hs688 (B).T
Melanoma* M14	3.9	Gastric ca. KATO III	5.6
Melanoma*	0.0	Colon ca. SW-948	0.0
LOXIMVI
Melanoma* SK-	0.1	Colon ca. SW480	0.0
MEL-5
Squamous cell	0.9	Colon ca.* (SW480 met)	0.0
carcinoma SCC-4		SW620
Testis Pool	3.8	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	0.0
Prostate Pool	5.6	Colon ca. CaCo-2	0.0
Placenta	0.4	Colon cancer tissue	2.3
Uterus Pool	1.2	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-	0.0	Colon ca. Colo-205	0.9
3
Ovarian ca. SK-OV-3	0.7	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-	0.1	Colon Pool	5.0
4
Ovarian ca. OVCAR-	4.6	Small Intestine Pool	3.6
5
Ovarian ca. IGROV-1	0.0	Stomach Pool	2.0
Ovarian ca. OVCAR-	0.2	Bone Marrow Pool	3.3
8
Ovary	12.5	Fetal Heart	1.8
Breast ca. MCF-7	0.0	Heart Pool	2.3
Breast ca. MDA-MB-231	3.6	Lymph Node Pool	0.0
Breast ca. BT 549	16.5	Fetal Skeletal Muscle	3.5
Breast ca. T47D	0.0	Skeletal Muscle Pool	2.5
Breast ca. MDA-N	2.0	Spleen Pool	22.7
Breast Pool	3.8	Thymus Pool	21.8
Trachea	3.9	CNS cancer (glio/astro)	0.2
		U87-MG
Lung	3.6	CNS cancer (glio/astro)	6.2
		U-118-MG
Fetal Lung	10.1	CNS cancer (neuro; met) SK-N-AS	0.0
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-	2.1
		539
Lung ca. LX-1	0.0	CNS cancer (astro)	2.8
		SNB-75
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-	0.0
		19
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-	21.9
		295
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.8
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.8
Lung ca. NCI-H23	0.0	Brain (fetal)	0.1
Lung ca. NCI-H460	0.0	Brain (Hippocampus)	0.3
		Pool
Lung ca. HOP-62	0.8	Cerebral Cortex Pool	0.4
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.9
		Pool
Liver	0.1	Brain (Thalamus) Pool	1.6
Fetal Liver	0.6	Brain (whole)	0.6
Liver ca. HepG2	0.0	Spinal Cord Pool	1.2
Kidney Pool	10.7	Adrenal Gland	1.5
Fetal Kidney	3.3	Pituitary gland Pool	0.1
Renal ca. 786-0	1.2	Salivary Gland	0.9
Renal ca. A498	1.5	Thyroid (female)	0.3
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	1.4
Renal ca. UO-31	0.0	Pancreas Pool	2.9

[0685]

TABLE GC
Panel CNS_1.1
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6580,		Ag6580,
	Run		Run
Tissue Name	274223227	Tissue Name	274223227
Cing Gyr	6.7	BA17 PSP2	4.0
Depression2
Cing Gyr Depression	0.0	BA17 PSP	11.0
Cing Gyr PSP2	0.0	BA17	24.5
		Huntington's2
Cing Gyr PSP	7.3	BA17	10.0
		Huntington's
Cing Gyr	28.9	BA17	21.2
Huntington's2		Parkinson's2
Cing Gyr	63.3	BA17 Parkinson's	78.5
Huntington's
Cing Gyr	36.3	BA17	12.7
Parkinson's2		Alzheimer's2
Cing Gyr Parkinson's	41.5	BA17 Control2	26.1
Cing Gyr	0.0	BA17 Control	32.5
Alzheimer's2
Cing Gyr Alzheimer's	4.6	BA9 Depression2	3.8
Cing Gyr Control2	12.2	BA9 Depression	13.5
Cing Gyr Control	43.5	BA9 PSP2	1.7
Temp Pole	14.7	BA9 PSP	0.0
Depression2
Temp Pole PSP2	0.0	BA9	15.2
		Huntington's2
Temp Pole PSP	0.0	BA9	42.9
		Huntington's
Temp Pole	50.0	BA9 Parkinson's2	0.0
Huntington's
Temp Pole	0.0	BA9 Parkinson's	1.6
Parkinson's2
Temp Pole	33.7	BA9	11.1
Parkinson's		Alzheimer's2
Temp Pole	1.7	BA9 Alzheimer's	0.0
Alzheimer's2
Temp Pole	0.0	BA9 Control2	54.7
Alzheimer's
Temp Pole Control2	5.6	BA9 Control	4.6
Temp Pole Control	12.5	BA7 Depression	18.7
Glob Palladus	5.6	BA7 PSP2	0.0
Depression
Glob Palladus PSP2	0.0	BA7 PSP	10.2
Glob Palladus PSP	0.0	BA7	57.8
		Huntington's2
Glob Palladus	3.1	BA7	36.9
Parkinson's2		Huntington's
Glob Palladus	79.6	BA7 Parkinson's2	21.3
Parkinson's
Glob Palladus	12.5	BA7 Parkinson's	14.3
Alzheimer's2
Glob Palladus	13.4	BA7	0.0
Alzheimer's		Alzheimer's2
Glob Palladus	2.6	BA7 Control2	18.7
Control2
Glob Palladus Control	23.2	BA7 Control	18.3
Sub Nigra	13.2	BA4 Depression2	27.5
Depression2
Sub Nigra Depression	45.1	BA4 Depression	8.6
Sub Nigra PSP2	2.1	BA4 PSP2	0.0
Sub Nigra	100.0	BA4 PSP	2.4
Huntington's2
Sub Nigia	86.5	BA4	12.0
Huntington's		Huntington's2
Sub Nigra	63.7	BA4	20.0
Parkinson's2		Huntington's
Sub Nigra	26.6	BA4 Parkinson's2	75.3
Alzheimer's2
Sub Nigra Control2	1.6	BA4 Parkinson's	55.5
Sub Nigra Control	77.4	BA4	0.0
		Alzheimer's2
BA17 Depression2	43.5	BA4 Control2	14.2
BA17 Depression	29.1	BA4 Control	0.0

[0686] General_screening_panel_v1.6 Summary: Ag6580 Highest expression of this gene is seen in a gastric cancer cell line (CT=28.8). Moderate expression is also seen in brain and breast cancer cell lines, with low expression in melanoma and ovarian cancer cell lines. Modulation of this gene product may be useful in the treatment of cancer.

[0687] Among tissues with metabolic function, this gene is expressed at low but significant levels in adipose, adrenal gland, pancreas, and adult and fetal skeletal muscle and heart. This 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.

[0688] Panel CNS—1.1 Summary: Ag6580 This gene is expressed at low levels in the CNS on this panel. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0689] H. CG127897-01: Syntenin-2BETA

[0690] Expression of gene CG127897-01 was assessed using the primer-probe set Ag4757, described in Table HA.

TABLE HA
Probe Name Ag4757
Primers	Sequences	Length	Start Position	SEQ ID No
Forward	5′-gacaggatagtccagtggattg-3′	22	266	113
Probe	TET-5′-atgcacaaggacagcacaagccat-3′-TAMRA	24	293	114
Reverse	5′-gaagacctttcccttcttgatg-3′	22	328	115

[0691] CNS_neurodegeneration_v1.0 Summary: Ag4757 Expression of the CG127897-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0692] General_screening_panel_v1.4 Summary: Ag4757 Expression of the CG127897-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0693] Panel 4.1D Summary: Ag4757 Expression of the CG127897-01 gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0694] I. CG127936-01 and CG127936-02: PLK INTERACTING PROTEIN

[0695] Expression of gene CG127936-01 and full length physical clone CG127936-02 was assessed using the primer-probe set Ag4770, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB and IC. Please note that CG127936-02 represents a full-length physical clone of the CG127936-01 gene, validating the prediction of the gene sequence.

TABLE IA
Probe Name Ag4770
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-caagcctgtcttgttgctgt-3′	20	528	116
Probe	TET-5′-tggcgcaaagctcaagaagtctgtaa-3′-TAMRA	26	558	117
Reverse	5′-tttcctaaggtttggccaac-3′	20	588	118

[0696]

TABLE IB
General_screening panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4770,		Ag4770,
	Run		Run
Tissue Name	222350146	Tissue Name	222350146
Adipose	11.5	Renal ca. TK-10	23.7
Melanoma*	12.8	Bladder	35.6
Hs688 (A).T
Melanoma*	21.2	Gastric ca. (liver met.) NCI-N87	27.0
Hs688 (B).T
Melanoma* M14	1.0	Gastric ca. KATO III	0.0
Melanoma*	21.3	Colon ca. SW-948	14.5
LOXIMVI
Melanoma* SK-	12.2	Colon ca. SW480	53.2
MEL-5
Squamous cell	7.1	Colon ca.* (SW480 met)	42.6
carcinoma SCC-4		SW620
Testis Pool	27.9	Colon ca HT29	2.4
Prostate ca.* (bone met) PC-3	21.2	Colon ca HCT-116	38.4
Prostate Pool	12.9	Colon ca CaCo-2	12.2
Placenta	0.9	Colon cancer tissue	9.0
Uterus Pool	13.9	Colon ca SW1116	5.8
Ovarian ca. OVCAR-	48.6	Colon ca Colo-205	3.1
3
Ovarian ca. SK-OV-3	44.1	Colon ca. SW-48	5.0
Ovarian ca. OVCAR-	7.3	Colon Pool	35.4
4
Ovarian ca. OVCAR-5	30.8	Small Intestine Pool	33.0
Ovarian ca. IGROV-1	16.6	Stomach Pool	15.4
Ovarian ca. OVCAR-	13.6	Bone Marrow Pool	12.9
8
Ovary	20.3	Fetal Heart	25.3
Breast ca. MCF-7	11.3	Heart Pool	15.1
Breast ca. MDA-MB-	8.0	Lymph Node Pool	46.3
231
Breast ca. BT 549	64.2	Fetal Skeletal Muscle	7.7
Breast ca. T47D	51.1	Skeletal Muscle Pool	8.4
Breast ca. MDA-N	0.0	Spleen Pool	10.7
Breast Pool	38.7	Thymus Pool	27.0
Trachea	19.8	CNS cancer (glio/astro)	9.0
		U87-MG
Lung	14.5	CNS cancer (glio/astro)	89.5
		U-118-MG
Fetal Lung	69.7	CNS cancer (neuro;met)	55.5
		SK-N-AS
Lung ca. NCI-N417	7.2	CNS cancer (astro) SF-	7.2
		539
Lung ca. LX-1	46.3	CNS cancer (astro)	17.7
		SNB-75
Lung ca. NCI-H146	46.3	CNS cancer (glio) SNB-	16.4
		19
Lung ca. SHP-77	100.0	CNS cancer (glio) SF-	49.3
		295
Lung ca. A549	17.3	Brain (Amygdala) Pool	6.8
Lung ca. NCI-H526	10.4	Brain (cerebellum)	11.6
Lung ca. NCI-H23	41.2	Brain (fetal)	28.5
Lung ca. NCI-H460	37.6	Brain (Hippocampus)	10.2
		Pool
Lung ca HOP-62	10.4	Cerebral Cortex Pool	11.7
Lung ca NCI-H522	28.7	Brain (Substantia nigra)	8.7
		Pool
Liver	0.4	Brain (Thalamus) Pool	18.7
Fetal Liver	15.3	Brain (whole)	9.0
Liver ca. HepG2	8.9	Spinal Cord Pool	10.9
Kidney Pool	49.7	Adrenal Gland	8.1
Fetal Kidney	45.1	Pituitary gland Pool	13.3
Renal ca. 786-0	25.0	Salivary Gland	6.4
Renal ca. A498	7.6	Thyroid (female)	14.4
Renal ca. ACHN	19.6	Pancreatic ca. CAPAN2	6.8
Renal ca. UO-31	22.5	Pancreas Pool	30.6

[0697]

TABLE IC
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4770,		Ag4770,
	Run		Run
Tissue Name	204964145	Tissue Name	204964145
Secondary Th1 act	29.7	HUVEC IL-1beta	21.3
Secondary Th2 act	26.8	HUVEC IFN gamma	24.7
Secondary Tr1 act	16.6	HUVEC TNF alpha + IFN gamma	11.0
Secondary Th1 rest	4.5	HUVEC TNF alpha + IL4	19.2
Secondary Th2 rest	12.8	HUVEC IL-11	17.8
Secondary Tr1 rest	8.5	Lung Microvascular EC	54.7
		none
Primary Th1 act	17.4	Lung Microvascular EC	28.9
		TNFalpha + IL-1beta
Primary Th2 act	27.0	Microvascular Dermal EC	35.6
		mone
Primary Tr1 act	31.9	Microsvasular Dermal EC	7.2
		TNFalpha + IL-1beta
Primary Th1 rest	8.8	Bronchial epithelium	35.8
		TNFalpha + IL1beta
Primary Th2 rest	9.2	Small airway epithelium	11.3
		none
Primary Tr1 rest	24.8	Small airway epithelium	16.2
		TNFalpha + IL-1beta
CD45RA CD4	37.1	Coronery artery SMC rest	15.4
lymphocyte act
CD45RO CD4	48.3	Coronery artery SMC	17.2
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	33.4	Astrocytes rest	13.4
Secondary CD8	27.7	Astrocytes TNFalpha + IL-	6.2
lymphocyte rest		1beta
Secondary CD8	8.8	KU-812 (Basophil) rest	73.2
lymphocyte act
CD4 lymphocyte none	18.6	KU-812 (Basophil)	100.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	17.3	CCD1106 (Keratinocytes)	30.8
CD95 CH11		none
LAK cells rest	16.5	CCD1106 (Keratinocytes)	13.0
		TNFalpha + IL-1beta
LAK cells IL-2	33.2	Liver cirrhosis	14.2
LAK cells IL-2 + IL-12	9.5	NCI-H292 none	47.6
LAK cells IL-2 + IFN	19.9	NCI-H292 IL-4	57.4
gamma
LAK cells IL-2 + IL-18	20.9	NCI-H292 IL-9	88.3
LAK cells	5.8	NCI-H292 IL-13	74.7
PMA/ionomycin
NK Cells IL-2 rest	33.9	NCI-H292 IFN gamma	80.1
Two Way MLR 3 day	14.4	HPAEC none	28.5
Two Way MLR 5 day	15.7	HPAEC TNF alpha + IL-1	18.3
		beta
Two Way MLR 7 day	5.8	Lung fibroblast none	32.5
PBMC rest	4.5	Lung fibroblast TNF alpha + IL-1 beta	17.4
PBMC PWM	17.3	Lung fibroblast IL-4	16.7
PBMC PHA-L	31.2	Lung fibroblast IL-9	27.0
Ramos (B cell) none	60.7	Lung fibroblast IL-13	17.7
Ramos (B cell)	74.7	Lung fibroblast IFN gamma	17.3
ionomycin
B lymphocytes PWM	34.2	Dermal fibroblast CCD1070	37.1
		rest
B lymphocytes CD40L	17.4	Dermal fibroblast CCD1070	36.9
and IL-4		TNF alpha
EOL-1 dbcAMP	27.5	Dermal fibroblast CCD1070	15.6
		IL-1 beta
EOL-I dbcAMP	7.7	Dermal fibroblast IFN	15.8
PMA/ionomycin		gamma
Dendritic cells none	9.3	Dermal fibroblast IL-4	31.4
Dendritic cells LPS	1.4	Dermal Fibroblasts rest	46.0
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.9
CD40
Monocytes rest	1.7	Neutrophils rest	1.9
Monocytes LPS	0.9	Colon	8.0
Macrophages rest	13.6	Lung	25.0
Macrophages LPS	1.0	Thymus	57.0
HUVEC none	26.4	Kidney	80.1
HUVEC starved	21.2

[0698] General_screening_panel_v1.4 Summary: Ag4770 Highest expression of the CG127936-01 gene is detected in lung cancer SHP-77 cell line (CT=29.9). Moderate levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0699] 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.

[0700] Interestingly, this gene is expressed at much higher levels in fetal (CT=32.2) when compared to adult liver (CT=40). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.

[0701] 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.

[0702] Panel 4.1D Summary: Ag4770 Highest expression of the CG127936-01 gene is detected in PMA/ionomycin treated basophils (CT=31.6). 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.

[0703] J. CG127954-01: Novel Intracellular Protein

[0704] Expression of gene CG127954-01 was assessed using the primer-probe set Ag4758, described in Table JA. Results of the RTQ-PCR runs are shown in Tables JB and JC.

TABLE JA
Probe Name Ag4758
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-acaaaccatggaagacttcaag-3′	22	1047	119
Probe	TET-5′-ccagaagaatatcctttaactccagaaaca-3′-TAMRA	30	1069	120
Reverse	5′-cttcccatttgttttcgtaaca-3′	22	1105	121

[0705]

TABLE JB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4758,		Ag4758,
	Run		Run
Tissue Name	224721732	Tissue Name	224721732
AD 1 Hippo	15.0	Control (Path) 3	9.8
		Temporal Ctx
AD 2 Hippo	33.9	Control (Path) 4	45.4
		Temporal Ctx
AD 3 Hippo	14.0	AD 1 Occipital Ctx	25.5
AD 4 Hippo	11.4	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	86.5	AD 3 Occipital Ctx	12.3
AD 6 Hippo	100.0	AD 4 Occipital Ctx	21.5
Control 2 Hippo	22.4	AD 5 Occipital Ctx	53.2
Control 4 Hippo	19.6	AD 6 Occipital Ctx	37.6
Control (Path) 3	14.9	Control 1 Occipital	8.5
Hippo		Ctx
AD 1 Temporal Ctx	20.4	Control 2 Occipital	39.5
		Ctx
AD 2 Temporal Ctx	32.8	Control 3 Occipital	20.9
		Ctx
AD 3 Temporal Ctx	10.6	Control 4 Occipital	12.3
		Ctx
AD 4 Temporal Ctx	24.0	Control (Path) 1	78.5
		Occipital Ctx
AD 5 Inf Temporal	78.5	Control (Path) 2	14.6
Ctx		Occipital Ctx
AD 5 SupTemporal	49.7	Control (Path) 3	6.0
Ctx		Occipital Ctx
AD 6 Inf Temporal	94.0	Control (Path) 4	23.3
Ctx		Occipital Ctx
AD 6 Sup Temporal	90.8	Control 1 Parietal	9.0
Ctx		Ctx
Control 1 Temporal	11.2	Control 2 Parietal	46.0
Ctx		Ctx
Control 2 Temporal	19.9	Control 3 Parietal	17.8
Ctx		Ctx
Control 3 Temporal	12.9	Control (Path) 1	78.5
Ctx		Parietal Ctx
Control 4 Temporal	11.3	Control (Path) 2	31.0
Ctx		Parietal Ctx
Control (Path) 1	62.0	Control (Path) 3	16.5
Temporal Ctx		Parietal Ctx
Control (Path) 2	30.8	Control (Path) 4	46.0
Temporal Ctx		Parietal Ctx

[0706]

TABLE JC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4758, Run		Ag4758, Run
Tissue Name	223110462	Tissue Name	223110462
Adipose	8.4	Renal ca. TK-10	10.7
Melanoma*	21.5	Bladder	17.9
Hs688(A).T
Melanoma*	17.3	Gastric ca. (liver met.)	54.3
Hs688(B).T		NCI-N87
Melanoma* M14	1.1	Gastric ca. KATO III	16.0
Melanoma*	9.1	Colon ca. SW-948	1.1
LOXIMVI
Melanoma* SK-	12.2	Colon ca. SW480	20.9
MEL-5
Squamous cell	2.3	Colon ca.* (SW480 met)	11.6
carcinoma SCC-4		SW620
Testis Pool	20.4	Colon ca. HT29	5.3
Prostate ca.* (bone	27.9	Colon ca. HCT-116	8.8
met) PC-3
Prostate Pool	8.2	Colon ca. CaCo-2	32.3
Placenta	0.7	Colon cancer tissue	8.0
Uterus Pool	10.4	Colon ca. SW1116	1.4
Ovarian ca. OVCAR-3	12.0	Colon ca. Colo-205	0.3
Ovarian ca. SK-OV-3	7.8	Colon ca. SW-48	0.3
Ovarian ca. OVCAR-4	6.0	Colon Pool	24.0
Ovarian ca. OVCAR-5	16.2	Small Intestine Pool	24.3
Ovarian ca. IGROV-1	9.2	Stomach Pool	11.5
Ovarian ca. OVCAR-8	8.5	Bone Marrow Pool	9.0
Ovary	12.9	Fetal Heart	4.1
Breast ca. MCF-7	3.7	Heart Pool	10.7
Breast ca. MDA-MB-	4.8	Lymph Node Pool	30.6
231
Breast ca. BT 549	14.1	Fetal Skeletal Muscle	4.3
Breast ca. T47D	30.6	Skeletal Muscle Pool	3.6
Breast ca. MDA-N	0.7	Spleen Pool	4.9
Breast Pool	20.4	Thymus Pool	14.6
Trachea	14.4	CNS cancer (glio/astro)	4.3
		U87-MG
Lung	15.0	CNS cancer (glio/astro)	12.4
		U-118-MG
Fetal Lung	100.0	CNS cancer (neuro: met)	15.6
		SK-N-AS
Lung ca. NCI-N417	1.3	CNS cancer (astro) SF-	11.2
		539
Lung ca. LX-1	3.7	CNS cancer (astro)	29.9
		SNB-75
Lung ca. NCI-H146	6.7	CNS cancer (glio) SNB-	9.2
		19
Lung ca. SHP-77	24.0	CNS cancer (glio) SF-	25.7
		295
Lung ca. A549	6.3	Brain (Amygdala) Pool	9.7
Lung ca. NCI-H526	4.5	Brain (cerebellum)	14.9
Lung ca. NCI-H23	11.7	Brain (fetal)	13.7
Lung ca. NCI-H460	3.2	Brain (Hippocampus)	19.5
		Pool
Lung ca. HOP-62	11.8	Cerebral Cortex Pool	23.5
Lung ca. NCI-H522	16.5	Brain (Substantia nigra)	17.1
		Pool
Liver	0.0	Brain (Thalamus) Pool	31.9
Fetal Liver	8.4	Brain (whole)	7.3
Liver ca. HepG2	5.6	Spinal Cord Pool	23.5
Kidney Pool	38.7	Adrenal Gland	1.5
Fetal Kidney	33.4	Pituitary gland Pool	5.1
Renal ca. 786-0	24.5	Salivary Gland	1.3
Renal ca. A498	9.0	Thyroid (female)	8.7
Renal ca. ACHN	16.3	Pancreatic ca. CAPAN2	6.9
Renal ca. UO-31	25.7	Pancreas Pool	24.1

[0707] CNS_neurodegeneration_v1.0 Summary: Ag4758 This panel does not show differential expression of this gene in Alzheimer's disease. However, this profile confirms the expression of this gene at moderate levels in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.

[0708] General_screening_panel_v1.4 Summary: Ag4758 This gene is widely expressed at low levels in this panel, with highest expression in fetal lung (CT=30). In addition, this gene is expressed at much higher levels in fetal lung tissue when compared to expression in the adult counterpart (CT=33). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[0709] This gene is also expressed at low levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0710] Panel 4.1D Summary: Ag4758 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0711] K. CG128132-01: RAL-A EXCHANGE FACTOR RALGPS2

[0712] Expression of gene CG128132-01 was assessed using the primer-probe set Ag4760, described in Table KA. Results of the RTQ-PCR runs are shown in Tables KB, KC and KD.

TABLE KA
Probe Name Ag4760
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-agcttaaagatgacaccttgca-3′	22	836	122
Probe	TET-5′-tgtcagatttaacatacatcgattcagca-3′-TAMRA	29	879	123
Reverse	5′-ttctagaatgctgccagttgat-3′	22	913	124

[0713]

TABLE KB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4760, Run		Ag4760, Run
Tissue Name	224721733	Tissue Name	224721733
AD 1 Hippo	10.4	Control (Path) 3	2.0
		Temporal Ctx
AD 2 Hippo	32.5	Control (Path) 4	29.7
		Temporal Ctx
AD 3 Hippo	18.2	AD 1 Occipital Ctx	21.0
AD 4 Hippo	4.3	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	88.3	AD 3 Occipital Ctx	5.8
AD 6 Hippo	100.0	AD 4 Occipital Ctx	8.3
Control 2 Hippo	29.1	AD 5 Occipital Ctx	50.7
Control 4 Hippo	12.2	AD 6 Occipital Ctx	18.7
Control (Path) 3	5.4	Control 1 Occipital	2.9
Hippo		Ctx
AD 1 Temporal Ctx	22.5	Control 2 Occipital	48.0
		Ctx
AD 2 Temporal Ctx	29.3	Control 3 Occipital	11.6
		Ctx
AD 3 Temporal Ctx	7.1	Control 4 Occipital	4.1
		Ctx
AD 4 Temporal Ctx	14.3	Control (Path) 1	73.7
		Occipital Ctx
AD 5 Inf Temporal	73.7	Control (Path) 2	6.8
Ctx		Occipital Ctx
AD 5 Sup Temporal	96.6	Control (Path) 3	1.9
Ctx		Occipital Ctx
AD 6 Inf Temporal	46.0	Control (Path) 4	13.7
Ctx		Occipital Ctx
AD 6 Sup Temporal	46.0	Control 1 Parietal	4.6
Ctx		Ctx
Control 1 Temporal	2.9	Control 2 Parietal	49.7
Ctx		Ctx
Control 2 Temporal	30.8	Control 3 Parietal	11.3
Ctx		Ctx
Control 3 Temporal	12.4	Control (Path) 1	46.0
Ctx		Parietal Ctx
Control 3 Temporal	5.4	Control (Path) 2	20.4
Ctx		Parietal Ctx
Control (Path) 1	48.3	Control (Path) 3	2.9
Temporal Ctx		Parietal Ctx
Control (Path) 2	30.4	Control (Path) 4	20.2
Temporal Ctx		Parietal Ctx

[0714]

TABLE KC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4760, Run		Ag4760, Run
Tissue Name	223110477	Tissue Name	223110477
Adipose	0.0	Renal ca. TK-10	27.0
Melanoma*	27.5	Bladder	0.0
Hs688(A).T
Melanoma*	16.0	Gastric ca. (liver met.)	42.6
Hs688(B).T		NCI-N87
Melanoma* M14	59.9	Gastric ca. KATO III	20.2
Melanoma*	4.8	Colon ca. SW-948	4.8
LOXIMVI
Melanoma* SK-	27.2	Colon ca. SW480	24.1
MEL-5
Squamous cell	14.3	Colon ca.* (SW480 met)	6.8
carcinoma SCC-4		SW620
Testis Pool	36.6	Colon ca. HT29	15.3
Prostate ca.* (bone	60.7	Colon ca. HCT-116	21.3
met) PC-3
Prostate Pool	7.0	Colon ca. CaCo-2	34.9
Placenta	0.9	Colon cancer tissue	13.0
Uterus Pool	3.8	Colon ca. SW1116	5.1
Ovarian ca. OVCAR-3	36.9	Colon ca. Colo-205	3.6
Ovarian ca. SK-OV-3	54.0	Colon ca. SW-48	4.9
Ovarian ca. OVCAR-4	30.1	Colon Pool	10.7
Ovarian ca. OVCAR-5	50.7	Small Intestine Pool	8.5
Ovarian ca. IGROV-1	10.2	Stomach Pool	6.9
Ovarian ca. OVCAR-8	9.2	Bone Marrow Pool	0.0
Ovary	4.3	Fetal Heart	4.5
Breast ca. MCF-7	12.7	Heart Pool	2.6
Breast ca. MDA-MB-231	35.4	Lymph Node Pool	11.1
Breast ca. BT 549	100.0	Fetal Skeletal Muscle	5.8
Breast ca. T47D	85.9	Skeletal Muscle Pool	2.2
Breast ca. MDA-N	20.3	Spleen Pool	25.9
Breast Pool	9.3	Thymus Pool	15.6
Trachea	9.5	CNS cancer (glio/astro)	14.0
		U87-MG
Lung	1.7	CNS cancer (glio/astro)	36.9
		U-118-MG
Fetal Lung	7.3	CNS cancer (neuro: met)	0.3
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-	5.6
		539
Lung ca. LX-1	17.1	CNS cancer (astro)	51.1
		SNB-75
Lung ca. NCI-H146	5.7	CNS cancer (glio) SNB-	10.6
		19
Lung ca. SHP-77	1.0	CNS cancer (glio) SF-	12.3
		295
Lung ca. A549	28.5	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	16.2	Brain (cerebellum)	0.0
Lung ca. NCI-H23	15.3	Brain (fetal)	2.2
Lung ca. NCI-H460	2.1	Brain (Hippocampus)	0.2
		Pool
Lung ca. HOP-62	9.6	Cerebral Cortex Pool	0.6
Lung ca. NCI-H522	32.8	Brain (Substantia nigra)	0.9
		Pool
Liver	0.6	Brain (Thalamus) Pool	1.4
Fetal Liver	21.5	Brain (whole)	0.5
Liver ca. HepG2	11.6	Spinal Cord Pool	4.7
Kidney Pool	11.2	Adrenal Gland	0.0
Fetal Kidney	10.7	Pituitary gland Pool	2.6
Renal ca. 786-0	29.5	Salivary Gland	1.3
Renal ca. A498	4.7	Thyroid (female)	2.4
Renal ca. ACHN	19.6	Pancreatic ca. CAPAN2	54.0
Renal ca. UO-31	20.0	Pancreas Pool	10.4

[0715]

TABLE KD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4760, Run		Ag4760, Run
Tissue Name	204408190	Tissue Name	204408190
Secondary Th1 act	1.2	HUVEC IL-1beta	20.0
Secondary Th2 act	3.4	HUVEC IFN gamma	26.8
Secondary Tr1 act	2.6	HUVEC TNF alpha + IFN	15.4
		gamma
Secondary Th1 rest	1.6	HUVEC TNF alpha + IL4	13.9
Secondary Th2 rest	4.7	HUVEC IL-11	15.9
Secondary Tr1 rest	1.3	Lung Microvascular EC	24.3
		none
Primary Th1 act	1.5	Lung Microvascular EC	17.0
		TNFalpha + IL-1beta
Primary Th2 act	2.2	Microvascular Dermal EC	24.1
		none
Primary Tr1 act	1.6	Microsvasular Dermal EC	10.6
		TNFalpha + IL-1beta
Primary Th1 rest	2.7	Bronchial epithelium	11.7
		TNFalpha + IL1beta
Primary Th2 rest	2.0	Small airway epithelium	4.2
		none
Primary Tr1 rest	8.6	Small airway epithelium	10.2
		TNFalpha + IL-1beta
CD45RA CD4	31.4	Coronery artery SMC rest	11.2
lymphocyte act
CD45RO CD4	8.6	Coronery artery SMC	11.0
lymphocyte act		TNFalpha + IL-1beta
CD8 lymphocyte act	3.2	Astrocytes rest	11.5
Secondary CD8	2.1	Astrocytes TNFalpha + IL-	9.3
lymphocyte rest		1beta
Secondary CD8	0.3	KU-812 (Basophil) rest	0.2
lymphocyte act
CD4 lymphocyte none	8.1	KU-812 (Basophil)	0.6
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	6.3	CCD1106 (Keratinocytes)	18.0
CD95 CH11		none
LAK cells rest	16.3	CCD1106 (Keratinocytes)	22.1
		TNFalpha + IL-1beta
LAK cells IL-2	5.9	Liver cirrhosis	6.4
LAK cells IL-2 + IL-12	5.0	NCI-H292 none	24.1
LAK cells IL-2 + IFN	3.5	NCI-H292 IL-4	40.6
gamma
LAK cells IL-2 + IL-18	6.3	NCI-H292 IL-9	65.1
LAK cells	11.6	NCI-H292 IL-13	42.0
PMA/ionomycin
NK Cells IL-2 rest	15.0	NCI-H292 IFN gamma	35.8
Two Way MLR 3 day	21.9	HPAEC none	10.6
Two Way MLR 5 day	7.1	HPAEC TNF alpha + IL-1	8.1
		beta
Two Way MLR 7 day	5.7	Lung fibroblast none	34.4
PBMC rest	9.6	Lung fibroblast TNF alpha +	38.2
		IL-1 beta
PBMC PWM	4.2	Lung fibroblast IL-4	17.7
PBMC PHA-L	10.5	Lung fibroblast IL-9	21.8
Ramos (B cell) none	84.7	Lung fibroblast IL-13	27.2
Ramos (B cell)	100.0	Lung fibroblast IFN gamma	52.5
ionomycin
B lymphocytes PWM	17.6	Dermal fibroblast CCD1070	49.3
		rest
B lymphocytes CD40L	95.3	Dermal fibroblast CCD1070	37.9
and IL-4		TNF alpha
EOL-1 dbcAMP	0.5	Dermal fibroblast CCD1070	38.7
		IL-1 beta
EOL-1 dbcAMP	0.5	Dermal fibroblast IFN	76.8
PMA/ionomycin		gamma
Dendritic cells none	5.9	Dermal fibroblast IL-4	70.2
Dendritic cells LPS	2.7	Dermal Fibroblasts rest	90.1
Dendritic cells anti-	2.1	Neutrophils TNFa + LPS	3.1
CD40
Monocytes rest	5.6	Neutrophils rest	18.4
Monocytes LPS	7.4	Colon	11.5
Macrophages rest	10.3	Lung	2.6
Macrophages LPS	2.7	Thymus	36.6
HUVEC none	14.8	Kidney	20.9
HUVEC starved	32.5

[0716] CNS_neurodegeneration_v1.0 Summary: Ag4760 This panel confirms the expression of the CG128132-01 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 this gene in treatment of central nervous system disorders.

[0717] General_screening_panel_v1.4 Summary: Ag4760 Highest expression of the CG128132-01 gene is detected in breast cancer BT 549 cell line (CT=25.9). Moderate to high levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0718] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, 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.

[0719] Interestingly, this gene is expressed at much higher levels in fetal (CT=28) when compared to adult liver (CT=33). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.

[0720] 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, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0721] Panel 4.1D Summary: Ag4760 Highest expression of the CG128132-01 gene is detected in ionomycin treated basophils (CT=28.9). This gene is expressed at low to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. 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.

[0722] L. CG128219-01: Adenosine-deaminase (Editase)

[0723] Expression of gene CG128219-01 was assessed using the primer-probe set Ag4773, described in Table LA.

Claims

1. An isolated polypeptide comprising the mature form of an amino acid sequenced selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44.

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 44.

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 44.

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 44.

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 44 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 44.

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 44.

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 44.

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 44.

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 44, or a complement of said nucleotide sequence.

26. A vector comprising the nucleic acid molecule of claim 20.

27. The vector of claim 26, further comprising a promoter operably linked to said nucleic acid molecule.

28. A cell comprising the vector of claim 26.

29. An antibody that immunospecifically binds to the polypeptide of claim 1.

30. The antibody of claim 29, wherein the antibody is a monoclonal antibody.

31. The antibody of claim 29, wherein the antibody is a humanized antibody.

32. A method for determining the presence or amount of the nucleic acid molecule of claim 20 in a sample, the method comprising: (a) providing said sample; (b) introducing said sample to a probe that binds to said nucleic acid molecule; and (c) determining the presence or amount of said probe bound to said nucleic acid molecule, thereby determining the presence or amount of the nucleic acid molecule in said sample.

33. The method of claim 32 wherein presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type

34. The method of claim 33 wherein the cell or tissue type is cancerous.

35. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the nucleic acid molecule of claim 20 in a first mammalian subject, the method comprising: a) measuring the level of expression of the nucleic acid in a sample from the first mammalian subject; and b) comparing the level of expression of said nucleic acid in the sample of step (a) to the level of expression of the nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of expression of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

36. A method of producing the polypeptide of claim 1, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.

37. The method of claim 36 wherein the cell is a bacterial cell.

38. The method of claim 36 wherein the cell is an insect cell.

39. The method of claim 36 wherein the cell is a yeast cell.

40. The method of claim 36 wherein the cell is a mammalian cell.

41. A method of producing the polypeptide of claim 2, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.

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.