Patent Publication Number: US-2003236188-A1

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

Description:
RELATED APPLICATIONS  
     [0001] This application claims priority to U.S. Ser. No. 60/288,395, filed May 3, 2001, U.S. Ser. No. 60/289,087, filed May 7, 2001, U.S. Ser. No. 60/289,619, filed May 8, 2001, U.S. Ser. No. 60/289,818, filed May 9, 2001, U.S. Ser. No. 60/289,817, filed May 9, 2001, U.S. Ser. No. 60/322,646, filed Sep. 17, 2001, U.S. Ser. No. 60/290,194, filed May 11, 2001, U.S. Ser. No. 60/318,346, filed Sep. 10, 2001, U.S. Ser. No. 60/290,753, filed May 14, 2001, U.S. Ser. No. 60/291,189, May 15, 2001, U.S. Ser. No. 60/292,374, filed May 21, 2001, U.S. Ser. No. 60/293,107, filed May 23, 2001, U.S. Ser. No. 60/294,110, filed May 29, 2001, U.S. Ser. No. 60/293,747, filed May 25, 2001, and U.S. Ser. No. 60/294,434, filed May 30, 2001, each of which is incorporated by reference in its entirety. 
    
    
     
       FIELD OF THE INVENTION  
       [0002] The present invention is based in part on nucleic acids encoding proteins that are new members of the following protein families: Troponin T-like  Homo sapiens  proteins, ACF7-interacting proteins, DEOXYURIDINE 5′-TRIPHOSPHATE NUCLEOTIDOHYDROLASE PRECURSOR-like  Homo sapiens  proteins, Mitosis-associated-like  Homo sapiens  proteins, Progesterone Receptor-associated p48-like  Homo sapiens  proteins, Rho GEF-like  Homo sapiens  proteins, DELTEX3-like  Homo sapiens  proteins, PALLIDIN proteins, CAM-KINASE II INHIBITOR ALPHA proteins, Intracellular Proteins, D9 Splice Variant 2 proteins, Ribosomal Protein L39-like  Homo sapiens  proteins, CLATHRIN COAT ASSEMBLY PROTEIN AP17-like  Homo sapiens  proteins, Nuclear Proteins, Intracellular Protein-like  Homo sapiens  proteins, Syncoilin proteins, Von Ebner&#39;s Gland protein precursor-like  Homo sapiens  proteins, Q9H5Z6 Hypothetical Cytoplasmic Proteins, Clathrin Coat Associated Protein-like  Homo sapiens  proteins, Leucine Zipper Motif Containing Proteins, HYDROXYPROLINE-RICH GLYCOPROTEIN-like  Homo sapiens  proteins, HIC1 proteins, METALLOTHIONEIN-IK-like  Homo sapiens  proteins, Benzodiazepine Receptor Related-like Proteins, Hypothetical-like  Homo sapiens  proteins, Cytoplasmic Proteins, 40S Ribosomal Proteins, FIP-2 proteins, Myosin Light Chain 2 TRAP proteins, Helix-loop-Helix-like  Homo sapiens  proteins, SNRNP-like  Homo sapiens  proteins, PEROXISOME ASSEMBLY PROTEIN PEX10 (PEROXIN-10)-like  Homo sapiens  proteins, and gene containing NUDIX hydrolase domain-like  Homo sapiens  proteins.  
       [0003] The invention relates to 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.  
       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: Troponin T-like  Homo sapiens  proteins, ACF7-interacting proteins, DEOXYURIDINE 5′-TRIPHOSPHATE NUCLEOTIDOHYDROLASE PRECURSOR-like  Homo sapiens  proteins, Mitosis-associated-like  Homo sapiens  proteins, Progesterone Receptor-associated p48-like  Homo sapiens  proteins, Rho GEF-like  Homo sapiens  proteins, DELTEX3-like  Homo sapiens  proteins, PALLIDIN proteins, CAM-KINASE II INHIBITOR ALPHA proteins, Intracellular Proteins, D9 Splice Variant 2 proteins, Ribosomal Protein L39-like  Homo sapiens  proteins, CLATHRIN COAT ASSEMBLY PROTEIN AP17-like  Homo sapiens  proteins, Nuclear Proteins, Intracellular Protein-like  Homo sapiens  proteins, Syncoilin proteins, Von Ebner&#39;s Gland protein precursor-like  Homo sapiens  proteins, Q9H5Z6 Hypothetical Cytoplasmic Proteins, Cathrin Coat Associated Protein-like  Homo sapiens  proteins, Leucine Zipper Motif Containing Proteins, HYDROXYPROLINE-RICH GLYCOPROTEIN-like  Homo sapiens  proteins, HIC1 proteins, METALLOTHIONEIN-IK-like  Homo sapiens  proteins, Benzodiazepine Receptor Related-like Proteins, Hypothetical-like  Homo sapiens  proteins, Cytoplasmic Proteins, 40S Ribosomal Proteins, FIP-2 proteins, Myosin Light Chain 2 TRAP proteins, Helix-loop-Helix-like  Homo sapiens  proteins, SNRNP-like  Homo sapiens  proteins, PEROXISOME ASSEMBLY PROTEIN PEX10 (PEROXIN-10)-like  Homo sapiens  proteins, and gene containing NUDIX hydrolase domain-like  Homo sapiens  proteins. The novel polynucleotides and polypeptides are referred to herein as NOV1a, NOV1b, NOV2a, NOV3a, NOV3b, NOV4a, NOV5a, NOV6a, NOV7a, NOV8a, NOV9a, NOV10a, NOV11a, NOV12a, NOV13a, NOV 14a, NOV15a, NOV 16a, NOV16b, NOV17a, NOV17b, NOV18a, NOV19a, NOV20a, NOV21a, NOV22a, NOV23a, NOV24a, NOV25a, NOV26a, NOV27a, NOV28a, NOV29a, NOV29b, NOV30a, NOV30b, NOV31a, NOV32a, NOV33a, NOV34a, NOV35a, and NOV36a. 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 molecule encoding a NOVX polypeptide that includes a nucleic acid sequence that has identity to the nucleic acids disclosed in SEQ ID NO:2n−1, wherein n is an integer between 1 and 42. 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 42. 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 42.  
       [0007] 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 42) or a complement of said oligonucleotide. Also included in the invention are substantially purified NOVX polypeptides (SEQ ID NO:2n, wherein n is an integer between 1 and 42). 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, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 42, 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, transplantation, Von Hippel-Lindau (VHL) syndrome, Alzheimer&#39;s disease, stroke, tuberous sclerosis, hypercalcemia, Parkinson&#39;s disease, Huntington&#39;s disease, cerebral palsy, epilepsy, Lesch-Nyhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, neuroprotection, diabetes, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, renal tubular acidosis, IgA nephropathy, hypercalcemia, cirrhosis, transplantation, systemic lupus erythematosus, autoimmune disease, asthma, emphysema, scleroderma, allergy, adult respiratory distress syndrome (ARDS), lymphedema, allergies, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, autoimmune disease, allergies, immunodeficiencies, transplantation, graft versus host disease (GVHD), lymphedema, fertility, diabetes, pancreatitis, obesity, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host, hypercalcemia, ulcers, anemia, ataxia-telangiectasia, cancer, trauma, regeneration (in vitro and in vivo), viral infections, bacterial infections, parasitic infections and/or other pathologies and disorders of the like.  
       [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. By way of non-limiting 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.  
       [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                       NO       NOVX   Internal   (nucleic   SEQ ID NO       Assignment   Identification   acid)   (polypeptide)   Homology                                          1a   CG127269-02   1   2   Troponin T-like  Homo sapiens          1b   CG127269-04   3   4   Troponin T-like  Homo sapiens          2a   CG134069-01   5   6   ACF7-interacting protein        3a   CG134632-01   7   8   DEOXYURIDINE 5′-                       TRIPHOSPHATE                       NUCLEOTIDOHYDROLASE                       PRECURSOR-like  Homo sapiens           3b   CG134632-02   9   10   DEOXYURIDINE 5′-                       TRIPHOSPHATE                       NUCLEOTIDOHYDROLASE                       PRECURSOR-like  Homo sapiens          4a   CG139186-01   11   12   Mitosis-associated-like  Homo                            sapiens          5a   CG94620-01   13   14   Progesterone Receptor-associated                       p48-like  Homo sapiens          6a   CG94882-01   15   16   Rho GEF-like  Homo sapiens          7a   CG94915-01   17   18   DELTEX3-like  Homo sapiens          8a   CG94966-01   19   20   PALLIDIN        9a   CG95053-01   21   22   CAM-KINASE II INHIBITOR                       ALPHA       10a   CG95063-01   23   24   Intracellular Protein       11a   CG95072-01   25   26   D9 Splice Variant 2       12a   CG95217-01   27   28   Ribosomal Protein L39-like  Homo                            sapiens         13a   CG95261-01   29   30   CLATHRIN COAT ASSEMBLY                       PROTEIN AP17-like  Homo sapiens         14a   CG95292-01   31   32   Nuclear Protein       15a   CG95452-01   33   34   Intracellular Protein-like  Homo                            sapiens         16a   CG95504-01   35   36   Syncoilin       16b   CG95504-02   37   38   Syncoilin       17a   CG95589-01   39   40   Intracellular Protein-like  Homo                            sapiens         17b   CG95589-02   41   42   Intracellular Protein-like  Homo                            sapiens         18a   CG95598-01   43   44   Intracellular Protein       19a   CG95639-01   45   46   Von Ebner&#39;s Gland protein precursor-                       like  Homo sapiens         20a   CG95649-01   47   48   Q9H5Z6 Hypothetical Cytoplasmic                       Protein       21a   CG95775-01   49   50   Clathrin Coat Associated Protein-like                         Homo sapiens         22a   CG95942-01   51   52   Leucine Zipper Motif Containing                       Protein       23a   CG96211-01   53   54   Intracellular Protein       24a   CG96221-01   55   56   HYDROXYPROLINE-RICH                       GLYCOPROTEIN-like  Homo                            sapiens         25a   CG96394-01   57   58   HIC1       26a   CG96470-01   59   60   METALLOTHIONEIN-IK-like                         Homo sapiens         27a   CG96650-01   61   62   Benzodiazepine Receptor Related                       Proteins       28a   CG96682-01   63   64   Cytoplasmic Protein       29a   CG96704-01   65   66   40S Ribosomal Protein       29b   CG96704-02   67   68   40S Ribosomal Protein       30a   CG97090-01   69   70   FIP-2       30b   CG97090-02   71   72   FIP-2       31a   CG97134-01   73   74   Myosin Light Chain 2       32a   CG97219-01   75   76   TRAP       33a   CG97358-01   77   78   Helix-loop-Helix-like  Homo sapiens         34a   CG97378-01   79   80   SNRNP-like  Homo sapiens         35a   CG97966-01   81   82   PEROXISOME ASSEMBLY                       PROTEIN PEX10 (PEROXIN-10)-                       like  Homo sapiens         36a   CG99852-01   83   84   gene containing NUDIX hydrolase                       domain-like  Homo sapiens                    
 
       [0029] Table A indicates homology of NOVX nucleic acids 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] 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.  
       [0031] 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.  
       [0032] 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.  
       [0033] 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 versus diseased tissues, e.g., a variety of cancers.  
       [0034] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.  
       NOVX Clones  
       [0035] 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.  
       [0036] 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.  
       [0037] 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) biological defense weapon.  
       [0038] 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 42; (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 42, 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 42; (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 42, 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).  
       [0039] 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 42; (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 42, 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 42; (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 42, 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 42, 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.  
       [0040] 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 42; (b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, 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 42; 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 42, 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.  
       NOVX Nucleic Acids and Polypeptides  
       [0041] One aspect of the invention pertains to isolated nucleic acid molecules that encode NOVX polypeptides or biologically active portions thereof. Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify NOVX-encoding nucleic acids (e.g., NOVX 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.  
       [0042] An NOVX nucleic acid can encode a mature NOVX polypeptide. As used herein, a “mature” form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full-length gene product, encoded by the corresponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein. The product “mature” form arises, again by way of nonlimiting example, as a result of one or more naturally occurring processing steps as they may take place within the cell, or host cell, in which the gene product arises. Examples of such processing steps leading to a “mature” form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+1 to residue N remaining. Further as used herein, a “mature” form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristoylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination of any of them.  
       [0043] The term “probes”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), 100 nt, or as many as approximately, e.g., 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single- or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.  
       [0044] The term “isolated” nucleic acid molecule, as utilized herein, is one, which is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5′- and 3′-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.). Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material or culture medium when produced by recombinant techniques, or of chemical precursors or other chemicals when chemically synthesized.  
       [0045] A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, or a complement of this aforementioned nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, 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 2  nd  Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989; and Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley &amp; Sons, New York, N.Y., 1993.) A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template and appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to NOVX nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.  
       [0046] As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues, which oligonucleotide has a sufficient number of nucleotide bases to be used in a PCR reaction. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise portions of a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.  
       [0047] 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 42, 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 an NOVX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence shown SEQ ID NO:2n−1, wherein n is an integer between 1 and 42 is one that is sufficiently complementary to the nucleotide sequence shown SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, that it can hydrogen bond with little or no mismatches to the nucleotide sequence shown SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, thereby forming a stable duplex.  
       [0048] 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.  
       [0049] Fragments provided herein are defined as sequences of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, respectively, and are at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice. Derivatives are nucleic acid sequences or amino acid sequences formed from the native compounds either directly or by modification or partial substitution. Analogs are nucleic acid sequences or amino acid sequences that have a structure similar to, but not identical to, the native compound but differs from it in respect to certain components or side chains. Analogs may be synthetic or from a different evolutionary origin,and may have a similar or opposite metabolic activity compared to wild type. Homologs are nucleic acid sequences or amino acid sequences of a particular gene that are derived from different species.  
       [0050] 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.  
       [0051] Derivatives and analogs may be full length or other than full length, if the derivative or analog contains a modified nucleic acid or amino acid, as described below. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the aforementioned proteins under stringent, moderately stringent, or low stringent conditions. See e.g. Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley &amp; Sons, New York, N.Y., 1993, and below.  
       [0052] A “homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences encode those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for an 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 42, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.  
       [0053] An NOVX polypeptide is encoded by the open reading frame (“ORF”) of an NOVX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG “start” codon and terminates with one of the three “stop” codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bonafide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.  
       [0054] The nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g. from other tissues, as well as NOVX homologues from other vertebrates. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence SEQ ID NO:2n−1, wherein n is an integer between 1 and 42; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 42; or of a naturally occurring mutant of SEQ ID NO:2n−1, wherein n is an integer between 1 and 42.  
       [0055] Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In various embodiments, the probe further comprises a label group attached thereto, e.g. the label group can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express an NOVX protein, such as by measuring a level of an NOVX-encoding nucleic acid in a sample of cells from a subject e.g., detecting NOVX mRNA levels or determining whether a genomic NOVX gene has been mutated or deleted.  
       [0056] “A polypeptide having a biologically-active portion of an 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 SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, that encodes a polypeptide having an 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.  
       NOVX Nucleic Acid and Polypeptide Variants  
       [0057] The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences shown in SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences shown in SEQ ID NO:2n−1, wherein n is an integer between 1 and 42. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence shown in SEQ ID NO:2n, wherein n is an integer between 1 and 42.  
       [0058] In addition to the human NOVX nucleotide sequences shown in SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, 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 an 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.  
       [0059] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from the human SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, 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.  
       [0060] 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 42. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences at least 60% homologous to each other typically remain hybridized to each other.  
       [0061] 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.  
       [0062] 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.  
       [0063] 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 &amp; 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 the sequences SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, 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).  
       [0064] 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 42, 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×Denhardt&#39;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 &amp; Sons, N.Y., and Kriegler, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, N.Y.  
       [0065] In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, 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 &amp; Sons, N.Y., and Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, N.Y.; Shilo and Weinberg, 1981.  Proc Natl Acad Sci USA  78: 6789-6792.  
       Conservative Mutations  
       [0066] 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 SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, thereby leading to changes in the amino acid sequences of the encoded NOVX proteins, without altering the functional ability of said NOVX proteins. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence SEQ ID NO:2n, wherein n is an integer between 1 and 42. 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.  
       [0067] 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, wherein n is an integer between 1 and 42, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 45% homologous to the amino acid sequences SEQ ID NO:2n, wherein n is an integer between 1 and 42. 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 42; more preferably at least about 70% homologous SEQ ID NO:2n, wherein n is an integer between 1 and 42; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 42; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 42; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 42.  
       [0068] An isolated nucleic acid molecule encoding an NOVX protein homologous to the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 42, 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 42, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.  
       [0069] Mutations can be introduced into SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, 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 an 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 SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.  
       [0070] 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.  
       [0071] 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 an 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).  
       [0072] 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).  
       Antisense Nucleic Acids  
       [0073] 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 42, 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 an NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 42, or antisense nucleic acids complementary to an NOVX nucleic acid sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, are additionally provided.  
       [0074] In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding an 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).  
       [0075] 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).  
       [0076] Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).  
       [0077] 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 an 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.  
       [0078] In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other. See, e.g., Gaultier, et al., 1987.  Nucl. Acids Res.  15: 6625-6641. The antisense nucleic acid molecule can also comprise a 2′-o-methylribonucleotide (See, e.g., Inoue, et al. 1987.  Nucl. Acids Res.  15: 6131-6148) or a chimeric RNA-DNA analogue (See, e.g., Inoue, et al., 1987.  FEBS Lett.  215: 327-330.  
       Ribozymes and PNA Moieties  
       [0079] 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.  
       [0080] 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 an NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of an NOVX cDNA disclosed herein (i.e., SEQ ID NO:2n−1, wherein n is an integer between 1 and 42). 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 an 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.  
       [0081] 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.  
       [0082] 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 nucleobases 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 oligomers can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra; Perry-O&#39;Keefe, et al., 1996.  Proc. Natl. Acad. Sci. USA  93: 14670-14675.  
       [0083] 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., S 1  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&#39;Keefe, et al., 1996. supra).  
       [0084] 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 nucleobases, and orientation (see, Hyrup, et al., 1996. supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al., 1996. supra and Finn, et al., 1996.  Nucl Acids Res  24: 3357-3363. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g., 5′-(4-methoxytrityl)amino-5′-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5′ end of DNA. See, e.g., Mag, et al., 1989.  Nucl Acid Res  17: 5973-5988. PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5′ PNA segment and a 3′ DNA segment. See, e.g., Finn, et al., 1996. supra. Alternatively, chimeric molecules can be synthesized with a 5′ DNA segment and a 3′ PNA segment. See, e.g., Petersen, et al., 1975.  Bioorg. Med. Chem. Lett.  5: 1119-11124.  
       [0085] 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. W088/09810) 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.  
       NOVX Polypeptides  
       [0086] A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in SEQ ID NO:2n, wherein n is an integer between 1 and 42. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in SEQ ID NO:2n, wherein n is an integer between 1 and 42, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.  
       [0087] In general, an NOVX variant that preserves NOVX-like function includes any variant in which residues at a particular position in the sequence have been substituted by other amino acids, and further include the possibility of inserting an additional residue or residues between two residues of the parent protein as well as the possibility of deleting one or more residues from the parent sequence. Any amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.  
       [0088] 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, an NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.  
       [0089] 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.  
       [0090] 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.  
       [0091] 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 shown in SEQ ID NO:2n, wherein n is an integer between 1 and 42) that include fewer amino acids than the full-length NOVX proteins, and exhibit at least one activity of an 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 an NOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length.  
       [0092] 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.  
       [0093] In an embodiment, the NOVX protein has an amino acid sequence shown SEQ ID NO:2n, wherein n is an integer between 1 and 42. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 42, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 42, 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 SEQ ID NO:2n, wherein n is an integer between 1 and 42, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1 and 42.  
       Determining Homology Between Two or More Sequences  
       [0094] 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”).  
       [0095] 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 shown in SEQ ID NO:2n−1, wherein n is an integer between 1 and 42.  
       [0096] 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.  
       Chimeric and Fusion Proteins  
       [0097] The invention also provides NOVX chimeric or fusion proteins. As used herein, an NOVX “chimeric protein” or “fusion protein” comprises an NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An “NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to an NOVX protein SEQ ID NO:2n, wherein n is an integer between 1 and 42), 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 an NOVX fusion protein the NOVX polypeptide can correspond to all or a portion of an NOVX protein. In one embodiment, an NOVX fusion protein comprises at least one biologically-active portion of an NOVX protein. In another embodiment, an NOVX fusion protein comprises at least two biologically-active portions of an NOVX protein. In yet another embodiment, an NOVX fusion protein comprises at least three biologically-active portions of an 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.  
       [0098] 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.  
       [0099] In another embodiment, the fusion protein is an 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.  
       [0100] In yet another embodiment, the fusion protein is an 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 an NOVX ligand and an 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 an 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 an NOVX ligand.  
       [0101] An 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 &amp; Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). An 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.  
       NOVX Agonists and Antagonists  
       [0102] 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.  
       [0103] 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.  
       Polypeptide Libraries  
       [0104] 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 an NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of an 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 S 1  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.  
       [0105] 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.  
       Anti-NOVX Antibodies  
       [0106] Also 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, F ab , F ab , and F (ab′)2  fragments, and an F ab  expression library. In general, an antibody molecule 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 IgG 1 , IgG 2 , 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.  
       [0107] An isolated NOVX-related protein of the invention may be intended to serve as an antigen, or a portion or fragment thereof, and additionally 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 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.  
       [0108] In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX-related protein that is located on the surface of the protein, e.g., a hydrophilic region. A hydrophobicity analysis of the human NOVX-related protein sequence will indicate which regions of a NOVX-related protein 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. hat. Acad. Sci. USA  78: 3824-3828; Kyte and Doolittle 1982,  J. Mol. Biol.  157: 105-142, each of which is incorporated herein by reference in its 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.  
       [0109] 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.  
       [0110] 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 and Lane, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). Some of these antibodies are discussed below.  
       Polyclonal Antibodies  
       [0111] 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&#39;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).  
       [0112] 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).  
       Monoclonal Antibodies  
       [0113] The term “monoclonal antibody” (MAb) or “monoclonal antibody composition”, as used herein, refers to a population of antibody molecules that contain only one molecular species of antibody molecule consisting of a unique light chain gene product and a unique heavy chain gene product. In particular, the complementarity determining regions (CDRs) of the monoclonal antibody are identical in all the molecules of the population. MAbs thus contain an antigen binding site capable of immunoreacting with a particular epitope of the antigen characterized by a unique binding affinity for it.  
       [0114] 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.  
       [0115] 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.  
       [0116] 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).  
       [0117] 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). Preferably, antibodies having a high degree of specificity and a high binding affinity for the target antigen are isolated.  
       [0118] After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods. Suitable culture media for this purpose include, for example, Dulbecco&#39;s Modified Eagle&#39;s Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.  
       [0119] 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.  
       [0120] 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.  
       Humanized Antibodies  
       [0121] 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)).  
       Human Antibodies  
       [0122] Fully human antibodies relate to antibody molecules in which essentially the entire sequences 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).  
       [0123] 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)).  
       [0124] Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal&#39;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&#39;s genome. The human genes are incorporated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications. The preferred embodiment of such a nonhuman animal is a mouse, and is termed the Xenomouse™ as disclosed in PCT publications WO 96/33735 and WO 96/34096. This animal produces B cells which secrete fully human immunoglobulins. The antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies. Additionally, the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules.  
       [0125] 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.  
       [0126] 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.  
       [0127] 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.  
       F ab  Fragments and Single Chain Antibodies  
       [0128] 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 F ab  expression libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal F ab  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 F ab  fragment generated by reducing the disulfide bridges of an F (ab′)2  fragment; (iii) an F ab  fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) F v  fragments.  
       Bispecific Antibodies  
       [0129] 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.  
       [0130] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello,  Nature,  305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published 13 May 1993, and in Traunecker et al., 1991  EMBO J.,  10:3655-3659.  
       [0131] 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).  
       [0132] 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.  
       [0133] Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g. F(ab′) 2  bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al.,  Science  229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab′) 2  fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab′ fragments generated are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab′-TNB derivatives is then reconverted to the Fab′-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab′-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.  
       [0134] 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.  
       [0135] 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 (V H ) connected to a light-chain variable domain (V L ) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the V H  and V L  domains of one fragment are forced to pair with the complementary V L  and V H  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).  
       [0136] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al.,  J. Immunol.  147:60 (1991).  
       [0137] 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).  
       Heteroconjugate Antibodies  
       [0138] 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.  
       Effector Function Engineering  
       [0139] It can be desirable to modify the antibody of the invention with respect to effector function, so as to enhance, e.g., the effectiveness of the antibody in treating cancer. For example, cysteine residue(s) can be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region. The homodimeric antibody thus generated can have improved internalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al.,  J. Exp Med.,  176: 1191-1195 (1992) and Shopes, J. Immunol., 148:2918-2922 (1992). Homodimeric antibodies with enhanced anti-tumor activity can also be prepared using heterobifunctional cross-linkers as described in Wolff et al. Cancer Research, 53:2560-2565 (1993). Alternatively, an antibody can be engineered that has dual Fc regions and can thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design, 3:219-230 (1989).  
       Immunoconjugates  
       [0140] 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).  
       [0141] 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  212 Bi,  131 I,  131 In,  90 Y, and  186 Re.  
       [0142] 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.  
       [0143] 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.  
       [0144] 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.  
       [0145] Anti-NOVX antibodies may be used in methods known within the art relating to the localization and/or quantitation of an 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 for NOVX proteins, or derivatives, fragments, analogs or homologs thereof, that contain the antibody derived binding domain, are utilized as pharmacologically-active compounds (hereinafter “Therapeutics”).  
       [0146] An anti-NOVX antibody (e.g., monoclonal antibody) can be used to isolate an NOVX polypeptide by standard techniques, such as affinity chromatography or immunoprecipitation. An anti-NOVX antibody can facilitate the purification of natural NOVX polypeptide from cells and of recombinantly-produced NOVX polypeptide expressed in host cells. Moreover, an anti-NOVX antibody can be used to detect NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the NOVX protein. Anti-NOVX antibodies can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include  125 I,  131 I,  35 S or  3 H.  
       NOVX Recombinant Expression Vectors and Host Cells  
       [0147] Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding an 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.  
       [0148] The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably-linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).  
       [0149] 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.).  
       [0150] 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.  
       [0151] 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.  
       [0152] Examples of suitable inducible non-fusion  E. coli  expression vectors include pTrc (Amrann et al., (1988)  Gene  69:301-315) and pET 11 d (Studier et al., GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).  
       [0153] 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.  
       [0154] 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.).  
       [0155] 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).  
       [0156] In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987.  Nature  329: 840) and pMT2PC (Kaufman, et al., 1987.  EMBO J.  6: 187-195). When used in mammalian cells, the expression vector&#39;s control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, and simian virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al., MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.  
       [0157] 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; Byme and Ruddle, 1989.  Proc. Natl. Acad. Sci. USA  86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985.  Science  230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990.  Science  249: 374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989.  Genes Dev.  3: 537-546).  
       [0158] 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 - Trendy in Genetics,  Vol. 1(1) 1986.  
       [0159] 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.  
       [0160] 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.  
       [0161] 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.  
       [0162] 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).  
       [0163] 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.  
       Transgenic NOVX Animals  
       [0164] 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.  
       [0165] 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 SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, can be introduced as a transgene into the genome of a non-human animal. Alternatively, a non-human homologue of the human NOVX gene, such as a mouse NOVX gene, can be isolated based on hybridization to the human NOVX cDNA (described further supra) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably-linked to the NOVX transgene to direct expression of NOVX protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Pat. Nos. 4,736,866; 4,870,009; and 4,873,191; and Hogan, 1986. In: MANIPULATING THE MOUSE EMBRYO, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of the NOVX transgene in its genome and/or expression of NOVX mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene-encoding NOVX protein can further be bred to other transgenic animals carrying other transgenes.  
       [0166] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of an 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 SEQ ID NO:2n−1, wherein n is an integer between 1 and 42), 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 42, 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).  
       [0167] 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.  
       [0168] 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.  
       [0169] 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. Nail. Acad Sci. USA  89: 6232-6236. Another example of a recombinase system is the FLP recombinase system of  Saccharomyces cerevisiae . See, O&#39;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.  
       [0170] 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 G 0  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.  
       Pharmaceutical Compositions  
       [0171] 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&#39;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&#39;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.  
       [0172] 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.  
       [0173] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.  
       [0174] Sterile injectable solutions can be prepared by incorporating the active compound (e.g., an 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.  
       [0175] 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.  
       [0176] 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.  
       [0177] 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.  
       [0178] 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.  
       [0179] 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.  
       [0180] 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.  
       [0181] 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.  
       [0182] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.  
       Screening and Detection Methods  
       [0183] 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 an 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.  
       [0184] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.  
       Screening Assays  
       [0185] 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.  
       [0186] 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 an 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.  
       [0187] A “small molecule” as used herein, is meant to refer to a composition that has a molecular weight of less than about 5 kD and most preferably less than about 4 kD. Small molecules can be, e.g., nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids or other organic or inorganic molecules. Libraries of chemical and/or biological mixtures, such as fungal, bacterial, or algal extracts, are known in the art and can be screened with any of the assays of the invention.  
       [0188] Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt, et al., 1993.  Proc. Natl. Acad. Sci. U.S.A.  90: 6909; Erb, et al., 1994.  Proc. Natl. Acad. Sci. U.S.A.  91: 11422; Zuckermann, et al., 1994.  J. Med. Chem.  37:2678; Cho, et al., 1993.  Science  261: 1303; Carrell, et al., 1994.  Angew. Chem. Int. Ed. Engl.  33:2059; Carell, et al., 1994.  Angew. Chem. Int. Ed. Engl.  33:2061; and Gallop, et al., 1994.  J. Med. Chem.  37: 1233.  
       [0189] 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.).  
       [0190] 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 an 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  125 I,  35 S,  14 C, or  3 H, 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 an NOVX protein, wherein determining the ability of the test compound to interact with an 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.  
       [0191] 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 an NOVX target molecule. As used herein, a “target molecule” is a molecule with which an NOVX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses an 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. An NOVX target molecule can be a non-NOVX molecule or an NOVX protein or polypeptide of the invention. In one embodiment, an 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.  
       [0192] Determining the ability of the NOVX protein to bind to or interact with an 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 an 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 Ca 2+ , diacylglycerol, IP 3 , etc.), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising an 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.  
       [0193] In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting an 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 an NOVX protein, wherein determining the ability of the test compound to interact with an 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.  
       [0194] 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 an 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 an NOVX target molecule. For example, the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra.  
       [0195] In yet another embodiment, the cell-free assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with an NOVX protein, wherein determining the ability of the test compound to interact with an NOVX protein comprises determining the ability of the NOVX protein to preferentially bind to or modulate the activity of an NOVX target molecule.  
       [0196] 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, Triton® X-114, Thesit®, decanoyl-N-methylglucamide, Triton® X-100, 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).  
       [0197] 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.  
       [0198] 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.  
       [0199] 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.  
       [0200] In yet another aspect of the invention, the NOVX proteins can be used as “bait proteins” in a two-hybrid assay or three hybrid assay (see, e.g., U.S. Pat. No. 5,283,317; Zervos, et al., 1993.  Cell  72:223-232; Madura, et al., 1993.  J. Biol. Chem.  268: 12046-12054; Bartel, et al., 1993.  Biotechniques  14: 920-924; Iwabuchi, et al., 1993.  Oncogene  8: 1693-1696; and Brent WO 94/10300), to identify other proteins that bind to or interact with NOVX (“NOVX-binding proteins” or “NOVX-bp”) and modulate NOVX activity. Such NOVX-binding proteins are also likely to be involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway.  
       [0201] 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 an 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.  
       [0202] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.  
       Detection Assays  
       [0203] 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.  
       Chromosome Mapping  
       [0204] 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, SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, 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.  
       [0205] 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.  
       [0206] 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&#39;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.  
       [0207] 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.  
       [0208] 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).  
       [0209] 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.  
       [0210] 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.  
       [0211] 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.  
       Tissue Typing  
       [0212] The NOVX sequences of the invention can also be used to identify individuals from minute biological samples. In this technique, an individual&#39;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).  
       [0213] 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&#39;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&#39;s DNA and subsequently sequence it.  
       [0214] 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).  
       [0215] 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 predicted coding sequences, such as those in SEQ ID NO:2n−1, wherein n is an integer between 1 and 42, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.  
       Predictive Medicine  
       [0216] 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&#39;s Disease, Parkinson&#39;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 an NOVX gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with NOVX protein, nucleic acid expression, or biological activity.  
       [0217] 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.)  
       [0218] Yet another aspect of the invention pertains to monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX in clinical trials.  
       [0219] These and other agents are described in further detail in the following sections.  
       Diagnostic Assays  
       [0220] 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 42, 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.  
       [0221] An agent for detecting NOVX protein is an antibody capable of binding to NOVX protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab′) 2 ) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect NOVX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of NOVX mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of NOVX genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of NOVX protein include introducing into a subject a labeled anti-NOVX antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.  
       [0222] 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.  
       [0223] 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.  
       [0224] 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.  
       Prognostic Assays  
       [0225] 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.  
       [0226] 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).  
       [0227] The methods of the invention can also be used to detect genetic lesions in an 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 an 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 an NOVX gene; (ii) an addition of one or more nucleotides to an NOVX gene; (iii) a substitution of one or more nucleotides of an NOVX gene, (iv) a chromosomal rearrangement of an NOVX gene; (v) an alteration in the level of a messenger RNA transcript of an NOVX gene, (vi) aberrant modification of an 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 an NOVX gene, (viii) a non-wild-type level of an NOVX protein, (ix) allelic loss of an NOVX gene, and (x) inappropriate post-translational modification of an 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 an 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.  
       [0228] 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 an 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.  
       [0229] 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.  
       [0230] In an alternative embodiment, mutations in an 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.  
       [0231] 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.  
       [0232] 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).  
       [0233] 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 S 1  nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e.g., Cotton, et al., 1988.  Proc. Natl. Acad. Sci. USA  85: 4397; Saleeba, et al., 1992.  Methods Enzymol.  217:286-295. In an embodiment, the control DNA or RNA can be labeled for detection.  
       [0234] 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 an 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.  
       [0235] 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.  
       [0236] 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.  
       [0237] 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.  
       [0238] 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.  
       [0239] 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 an NOVX gene.  
       [0240] 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.  
       Pharmacogenomics  
       [0241] Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e.g., NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders (The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer&#39;s Disease, Parkinson&#39;s Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers.) In conjunction with such treatment, the pharmacogenomics (i.e., the study of the relationship between an individual&#39;s genotype and that individual&#39;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&#39;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.  
       [0242] 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.  
       [0243] 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 P450 enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite morphine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.  
       [0244] 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&#39;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 an NOVX modulator, such as a modulator identified by one of the exemplary screening assays described herein.  
       Monitoring of Effects During Clinical Trials  
       [0245] 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.  
       [0246] 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.  
       [0247] 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 an NOVX protein, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the pre-administration sample with the NOVX protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of NOVX to higher levels than detected, i.e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of NOVX to lower levels than detected, i.e., to decrease the effectiveness of the agent.  
       Methods of Treatment  
       [0248] The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant NOVX expression or activity. The disorders include cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, transplantation, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn&#39;s disease; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, and other diseases, disorders and conditions of the like.  
       [0249] These methods of treatment will be discussed more fully, below.  
       Disease and Disorders  
       [0250] 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.  
       [0251] 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.  
       [0252] 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).  
       Prophylactic Methods  
       [0253] 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, an 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.  
       Therapeutic Methods  
       [0254] 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 an NOVX protein, a peptide, an 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 an 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 an NOVX protein or nucleic acid molecule as therapy to compensate for reduced or aberrant NOVX expression or activity.  
       [0255] 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).  
       Determination of the Biological Effect of the Therapeutic  
       [0256] 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.  
       [0257] In various specific embodiments, in vitro assays may be performed with representative cells of the type(s) involved in the patient&#39;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.  
       Prophylactic and Therapeutic Uses of the Compositions of the Invention  
       [0258] The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders including, but not limited to: metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cancer, neurodegenerative disorders, Alzheimer&#39;s Disease, Parkinson&#39;s Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers.  
       [0259] As an example, a cDNA encoding the NOVX protein of the invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof. By way of non-limiting example, the compositions of the invention will have efficacy for treatment of patients suffering from: metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer&#39;s Disease, Parkinson&#39;s Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias.  
       [0260] 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.  
       [0261] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. In the following examples, a putative untranslated region upstream from the initiation codon and downstream from the termination codon are underlined, and the start and stop codons are in bold letters. 
     
    
    
     EXAMPLES  
     Example A  
     NOVX Clone Information  
     [0262] The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1A.  
               TABLE 1A                       NOV1 Sequence Analysis                                                SEQ ID NO:1   977 bp                     NOV1a,     CCCACCTTCACC   ATG TCTGACGAGGAAGTTGAACAGGTGGAGAGCAGTACGAAGAAG               CG127269-02 DNA   AAGAGGAAGCCCAGGAGGAAGAGGAAGTTCAAGAAGAGCAGAAACCGACACCCAAACT               Sequence   CACTGCTCCTAAGATCCCAGAAGGGGAGAAAGTCCACTTCCATGACATCCAGAAGAAG                   CGTCACAACAAAGACCTAATGGAGCTCCAGGCCCTCATCGACAGCCACTTTGAAGCCC                   GGAAGAAGGAGGAGGAGGAGCTGGTCGCTCTCAAAGAGAGAATCGAGAAGCGCCGTGC                   AGAGAGAGCGGAGCAGCAGAGGATTCGTGCAGAGAAGGAGAGGGAGCGCCAGAACAGA                   CTGGCGGAGGAAAAGGCCAGAAGGGAGGAGGAGGATGCCAAGAGGAGGGCAGAGGACG                   ACCTGAAGAAGAAGAAAGCTCTGTCTTCCATGGGAGCCAACTACAGCAGCTACCTGGC                   CAAGGCTGACCAGAAGAGAGGCAAGAAGCAGACAGCCCGGCAAATGAAGAAGAAGATT                   CTGGCTGAGAGACGCAAGCCGCTCAACATCGATCACCTTGGTGAAGACAAACTGAGGG                   ACAAGGCCAAGGAGCTCTGGGAGACCCTGCACCAGCTGGAGATTGACAAGTTCGAGTT                   TGGGGAGAAGCTGAAACGCCACAAATATGACATCACCACGCTCAGCACCCGCATTGAC                   CAGGCCCAGAAGCACAGCAAGAAGGCTGGGACCCCAGCCAAGCGCAAAGTCGGCGGGC                   GCTCGAAG TAG   AGAGGCCAGAAAGGCCCCTCGAGGCAGAGACCCTCCGCCCTCTTGCA                       CACCAGGGCCGCTCGTGGGACTCCACATCCTCCAGCCCCCACAATCCTGTCAGCCGCT                       CCCTGACAGTCCTCCGCGTGGAGAGCCCATCCCGGGGCGTCCCCCGCGTCTGTGTCCT                       TGCTGCCTTCATCCCCTGGGGCCTGTGAATAAAGCTGCAGAACCCCCTT                                       ORF Start: ATG at 13   ORF Stop: TAG at 763           SEQ ID NO:2   250 aa MW at 29735.2 kD                     NOV1a,   MSDEEVEQVEEQYEEEEEAQEEEEVQEEEKPRPKLTAPKIPECEKVDFDDIQKKRQNK               CG127269-02 Protein   DLMELQALIDSHFEARKKEEEELVALKERIEKRRAERAEQQRIRAEKERERQNRLAEE                   KARREEEDAKRRAEDDLKKKKALSSMGANYSSYLAKADQKRGKKQTAREMKKKILAER               Sequence   RKPLNIDHLGEDKLRDKAKELWETLHQLEIDKFEFGEKLKRQKYDITTLRSRIDQAQK                   HSKKAGTPAKGKVGGRWK                             SEQ ID NO:3   975 bp                     NOV1b,     CCCACCTTCACC   ATG TCTGACGAGGAAGTTGAACAGGTCGACGAGCAGTACGAAGAAG               CG127269-04 DNA   AAGAGGAAGCCCAGGAGGAAGAGGAAGTTCAAGAAGAGGAGAACCGAGACCCAAACT               Sequence   CACTGCTCCTAAGATCCCAGAAGGGGAGAAAGTGGACTTCGATGACATCCAGAAGAAG                   CGTCAGAACAAAGACCTAATGGAGCTCCAGGCCCTCATCCACAGCCACTTTGAAGCCC                   GGAAGAGGAGGACGACGAGCTGGTCGCTCTCAAAGAGAGAATCGACAAGCGCCGTGC                   AGAGAGAGCGGAGCAGCAGAGGATTCGTGCAGAGAAGGAGAGGGAGCGCCAGAACAGA                   CTGGCGGAGGAAAAGGCCAGAAGGGAGGAGGAGGATGCCAAGAGGAGGGCAGAGGACG                   ACCTGAAGAAGAAGAAAGCTCTGTCTTCCATGGGAGCCAACTACAGCAGCTACCTGGC                   CAAGGCTGACCAGAAGAGAGGCAAGAAGCAGACAGCCCGGGAAATGAAGAAGAAGATT                   CTGGCTGAGAGACGCAAGCCGCTCAACATCGATCACCTTGGTGAAGACAAACTGAGGG                   ACAAGGCCAAGGAGCTCTGGGAGACCCTGCACCAGCTGGAGATTGACAAGTTCGAGTT                   TGGGGACAAGCTGAAACGCCAGAAATATGACATCACCACGCTCACGAGCCGCATTGAC                   CAGCCCCAGAAGCACAGCAAGAAGGCTGGGACCCCAGCCAAGGGCAAAGTCGGCCCGC                   GCTGGAAG TAG   AGAGGCCAGAAAGGCCCTCGAGGCAGAGACCCTCCGCCCTCTTGCAC                       ACCAGGGCCCCTCGTGGGACTCCACATCCTCCACCCCCCACAATCCTGTCACGGGTCT                       CCCTGACGTCCTGCGGCTGGAGAGGCCATCCCGGGCCGTCCCCCGCGTCTGTGTCCTT                       GCTGCCTTCATCCCCTGGGGCCTGTGAATAAAGCTGCAGAACCCCCT                                       ORF Start: ATG at 13   ORF Stop: TAG at 763           SEQ ID NO:4   250 aa MW at 29735.2 kD                     NOV1b,   MSDEEVEQVEEQYEEEEEAQEEEEVQEEEKPRPKLTAPKIPEGEKVDFDDIQKKRQNK               CG127269-04 Protein   DLMELQALIDSHFEARKKEEEELVALKERIEKRRAERAEQQRIRAEKERERQNRLAEE               Sequence   KARREEEDAKRRAEDDLKKKKALSSMGANYSSYLAKADQKRGKKQTAREMKKKILAER                   RKPLNIDHLGEDKLRDKAKELWETLHQLEIDKFEFGEKLKRQKYDITTLRSRIDQAQK                   HSKKAGTPAKGKVGGRWK                  
 
     [0263] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 1B.  
               TABLE 1B                          Comparison of NOV1a against NOV1b.                             NOV1a   Identities/Similarities for       Protein Sequence   Residues/Match Residues   the Matched Region               NOV1b   30 . . . 250   163/221 (73%)           30 . . . 250   163/221 (73%)                  
 
     [0264] Further analysis of the NOV1a protein yielded the following properties shown in Table 1C.  
               TABLE 1C                       Protein Sequence Properties NOV1a                                        PSort   0.9916 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:                  
 
     [0265] A search of the NOVI a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1D.  
               TABLE 1D                          Geneseq Results for NOV1a                                         NOV1a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               AAB00136   Human fast twitch skeletal muscle    1 . . . 250   250/258 (96%)   e−137           Troponin subunit T -  Homo sapiens , 258    1 . . . 258   250/258 (96%)           aa. [WO200054770-A1, 21-SEP-2000]       AAW22599   Human fast twitch skeletal muscle    1 . . . 250   250/258 (96%)   e−137           troponin T -  Homo sapiens , 258 aa.    1 . . . 258   250/258 (96%)           [WO9730085-A1, 21-AUG-1997]       AAY91961   Human cytoskeleton associated protein    1 . . . 250   249/269 (92%)   e−134           16 (CYSKP-16) -  Homo sapiens , 269 aa.    1 . . . 269   249/269 (92%)           [WO200017355-A2, 30-MAR-2000]       AAW76636   Human cardiac HcTnT protein -  Homo       2 . . . 250   157/257 (61%)   2e−81              sapiens , 288 aa. [DE19815128-A1, 08-OCT-1998]   36 . . . 288   198/257 (76%)       AAW76638   Human cardiac HcTnT protein mutant    2 . . . 250   156/257 (60%)   1e−80            F1101 -  Homo sapiens , 288 aa.   36 . . . 288   197/257 (75%)           [DE19815128-A1, 08-OCT-1998]                  
 
     [0266] In a BLAST search of public sequence datbases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1E.  
               TABLE 1E                          Public BLASTP Results for NOV1a                                         NOV1a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               I53021   troponin T - human, 258 aa.   1 . . . 250   250/258 (96%)   e−137               1 . . . 258   250/258 (96%)       P45378   Troponin T, fast skeletal muscle isoform   2 . . . 250   249/257 (96%)   e−136           beta (Beta TnTF) -  Homo sapiens     1 . . . 257   249/257 (96%)           (Human), 257 aa.       Q9TS31   TROPONIN T BETA ISOFORM -   2 . . . 250   238/249 (95%)   e−132             Oryctolagus cuniculus  (Rabbit), 249 aa.   1 . . . 249   243/249 (97%)       P09739   Troponin T, fast skeletal muscle   2 . . . 250   240/258 (93%)   e−131           isoforms beta/alpha (Beta/alpha TnTF) -   1 . . . 258   244/258 (94%)             Rattus norvegicus  (Rat), 258 aa.       A24824   troponin T, fast skeletal muscle - rat,   1 . . . 250   241/272 (88%)   e−129           272 aa.   1 . . . 272   245/272 (89%)                  
 
     [0267] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1F.  
               TABLE 1F                          Domain Analysis of NOV1a                             Pfam   NOV1a   Identities/Similarities           Domain   Match Region   for the Matched Region   Expect Value               Troponin   54 . . . 196    56/190 (29%)   4.7e−42               133/190 (70%)                  
 
     Example 2  
     [0268] The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.  
               TABLE 2A                       NOV2 Sequence Analysis                                                SEQ ID NO:5   1447 bp                     NOV2a,     ATTTCTTATCTGTGTCAAGAGCTGCAATATTTGTTTTAACTATCTGCAAA   ATG GGGAA               CG134069-01 DNA   GCCACTCAGCAGACCAGACTGTTTACGTCAGAATCCCCCATGTGTAGGGAAGGGTGAA               Sequence   GAAGAGGAGGACCTAAATATCGAAGACTGTTACGTCCCACAGCGGTCAATCTATGATA                   CTGTTAGACTAAATGAACAGATAGACTCTGGTTCAAAAGGTAGTCTATCTTCCAGGCA                   TTTTACAGATCGAACTTTACCCTACAGTCACAGAACACTCGATGTTAGTTCTTTATGC                   TCTAATGGTGCCCTTACTTCTTCCAGTGTATTTGAGCTCACACCTCGGGAAGCTAACA                   AACTAGATGAAAAGATGATCTTTGATGCACTCAAACTAAATAGTGATATCATTCGAAC                   CACAGGATTACCTAAAGCCAAATCTCATGCGCAAAAGAAAGAGCATAGACGGTCATGG                   CGAATGTTTGTCCCGGCCAATTTTATGGATTATGCAAACAAAAGTGAAAGCTCTTTTG                   TTGAACCTGCTGATATGTCAGATGCTGTTACCAAGGCCAGCAAGTGCAGATCCGGTAC                   TAATTCTCTCACTTCGGAGGAGGATGACTCTGGTTTATGTAGCCCTCCAGCAGAGAGG                   GAAGAAAAACAGGGCATTTTAACTGGAGACCAGTCACGAATTAAAAGTTTGTCTTCTA                   CTGAAGATATTCTTGTAACAGACCAATACAGACCATTTTTTTCTGTTAATTCCATTAG                   CGAACAGAAAATCCCACTGCTTTCATGTCAAAGTGCCCACCCTGATGAAAATTTCAAA                   ATGATTTTACATGATGTTTCTCCACTAGAGGAAGCAAAACATGTAAATGGTCAAAGGG                   AAATCCACGATGAAAATTGTTGCCTGCAGAATAATTTGAAAGAGAGCCCTGTGAAGTG                   TGACCCATTAATTATGCCAAGAAATAGAGAAAATGAGCATATTTTTAACCTTGGAGAA                   GAGGACGAAACATACGGACCTGGAGAATCCCAAATCACAGCACAAAGTAGGGAACTCT                   TGAAGGATTCCCCTCAAGATTTAGATCTCTCTCACACAGATCTAGGGGAGAGTGATGT                   AGATTGTGGTAGCACCAGCTTAGTAGAAAATGTGACACTTTTGACACAATATGATTCA                   GGAGAATGCAACATTGCATCTAAAGAGGAAGTGGAGGCTCCTCTTTCTGCCCAGGAGA                   GCGAAATGCTCTATAAGAAGTTCTCCCTGAAATTCGTATCAGCAAGAAAGAAAGCAGC                   ACCCAGAAAAACACGGGCCCAGGCAGGAATATTGGACACAGTCTGCAATGGCTTTCAG                   TTGGTTCAGGTAATTCATGGAAATATGAAACTCTGCAGTGTCAAAAGTTTGCGGTTCT                   GCT AA   AAGTTTGTGGTTCTGTTTCAGAGTGGTCACTAGTGTTTCTAATAATAATG                                       ORF Start: ATG at 51   ORF Stop: TAA at 1395           SEQ ID NO:6   448 aa MW at 50011.3 kD                     NOV2a,   MGKPLSRPDCLRQNPPCVGKGEEEEDLNIEDCYVPQRSIYDTVRLNEQIDSGSKGSLS               CG134069-01   Protein SRHFTDRTLPYSHRTLDVSSLCSNGALTSSSVFELRGREANKLDEKMIFDALKLNSDI               Sequence   IRTTGLPKAKSHAEKKEHRRSWRMFVPANFD4DYANKSESSFVEPADMSDAVTKASKCR                   WGTNSLTSEEDDSGLCSPPAEREEKQGILTGDQSRIKSLSSTEDILVTDQYRPFFSVN                   SISEQKIPLLSCQSAHPDENFKMVILHDVSPLEEAKHVNGQREIHDENCCLQNNLKESP                   VKCDPLIMPRNRENEHFNLGEEDETYGPGESQITAQSRELLKDSPQDLDLSHTDLGE                   SDVDCGSTSLVENVTLLTQYDSGECNIASKEEVEAPLSAQESEMLYKKFSLKFVSARK                   KAAPRKTGAQAGILDTVCNGFQLVQVIHGNMKLCSVKSLRFC                  
 
     [0269] Further analysis of the NOV2a protein yielded the following properties shown in Table 2B.  
               TABLE 2B                       Protein Sequence Properties NOV2a                                        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:                  
 
     [0270] A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2C.  
               TABLE 2C                          Geneseq Results for NOV2a                                         NOV2a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value                                         AAB18278     Plasmodium falciparum  chromosome 2   153 . . . 407   53/259 (20%)   0.054           related protein SEQ ID NO: 135 -    84 . . . 325   110/259 (42%)              Plasmodium falciparum , 665 aa.           [WO200025728-A2, 11-MAY-2000]       AAB01674   FIS2 protein sequence -  Arabidopsis     114 . . . 224   33/118 (27%)   0.36             thaliana , 813 aa. [WO200016609-A1, 30-MAR-2000]   262 . . . 376   49/118 (40%)       AAG06245     Arabidopsis thaliana  protein fragment SEQ   303 . . . 432   33/141 (23%)   0.36           ID NO: 2948 -  Arabidopsis thaliana , 376    94 . . . 234   55/141 (38%)           aa. [EP1033405-A2, 06-SEP-2000]       AAG06244     Arabidopsis thaliana  protein fragment SEQ   303 . . . 432   33/141 (23%)   0.36           ID NO: 2947 -  Arabidopsis thaliana , 386   104 . . . 244   55/141 (38%)           aa. [EP1033405-A2, 06-SEP-2000]       AAM41000   Human polypeptide SEQ ID NO: 5931 -    194 . . . 402   46/218 (21%)   0.47             Homo sapiens , 1988 aa. [WO200153312-    927 . . . 1125   90/218 (41%)           A1, 26-JUL-2001]                  
 
     [0271] 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 2D.  
               TABLE 2D                          Public BLASTP Results for NOV2a                                         NOV2a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                         O96229   HYPOTHETICAL 78.6 KDA   153 . . . 407   53/259 (20%)   0.14           PROTEIN -  Plasmodium falciparum ,    84 . . . 325   110/259 (42%)            665 aa.       Q9FGX0   GB|AAC55944.1 -  Arabidopsis     236 . . . 396   40/169 (23%)   0.24             thaliana  (Mouse-ear cress), 569 aa.   327 . . . 488   67/169 (38%)       Q93ZJ6   AT2G32240/F22D22.1 -  Arabidopsis     150 . . . 390   52/256 (20%)   0.41             thaliana (Mouse-ear cress), 568 aa.     278 . . . 528   108/256 (41%)        P08799   Myosin II heavy chain, non muscle -   292 . . . 412   34/121 (28%)   0.54             Dictyostelium discoideum  (Slime   816 . . . 927   55/121 (45%)           mold), 2116 aa.       AAL99108   HYPOTHETICAL 35.2 KDA    77 . . . 261   40/188 (21%)   0.71           PROTEIN -  Dictyostelium discoideum      47 . . . 216   76/188 (40%)           (Slime mold), 315 aa.                  
 
     [0272] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2E.  
               TABLE 2E                       Domain Analysis of NOV2a                                                Domain   NOV2a   Identities/   Expect Value       Pfam   Match Region   Similarities               for the Matched Region                  
 
     Example 3  
     [0273] 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   11520 bp                     NOV3a,     TCACCGGCGCCGAGATGCGGTTCCGGCGCTTAGGGCGCCGCTAAACTCAGAGCCCGGG                 CG134632-01 DNA     AGTCATGGCTGCGGGCGGTGCCGCCCCAGGTAAATCAGTCCAGGAGCAGGGCCCGGGC                 Sequence     CTGGCGTACACTCTCGGAAAAATGGGGGCCAGAGCAAACAAGAAGAGCGAAAGCAAGA                       GGGCTAGGCAGCCAGAGGCGGCAGCAAGACTCAAGACGCCAACGGCGCCGTCTTCCTG                       GGGCCCCAGGGCCTGCGCCATCCCTGGCCTGCCGGGGCACCGCCTCTCCACGCCCCTC                       GTCCGGCGGCGGCTGCGACTGCTTCCGAGGTCATGTTCCCAGGACGGGCGCGTCTTCA                       GGGTGGAAGCCTGGCGCACGTCCGGAGGTGCCGAGGACCCAACCAGCCCAAACTCTGG                       GGGAA   ATG ACTCCCCTCTCCCCTCGCCCCCCGCTCTGCTACCATTTCCTTACGTCTCT                   GCTTCGCTCACCGATGCAAAACGCGCGAGGCGCACGGCAGAGGGCCGAAGCCGCGGTA                   CTCTCCGGGCCAGGCCCGCCCCTCGGCCCCCCCGCGCAGCACGGGATTCCCCGGCCGC                   TGTCCACCGCTGGCCGCCTCAGCCAAGGCTCCCGCGGAGCCAGTACAGTCGGGGCCGC                   TGGCTGGAAGGGCGAGCTTCCTAAGGCGGGGGGAAGCCCGGCGCCGGGGCCGGAGACA                   CCCGCCATTTCACCCAGTAAGCGGGCCCGGCCTGCGGAGGTGGGCGGCATGCAGCTCC                   GCTTTCCCCCGCTCTCCGAGCACGCCACGGCCCCCACCCGGGGCTCCCCGCGCGCCGC                   GGGCTACGACCTGTACAGTGCCTATGATTACACAATACCACCTATGGAGAAAGCTGTT                   GTGAAAACGGACATTCAGATAGCGCTCCCTTCTCGGTGTTATGGAAGAGTCGCTCCAC                   GGTCAGGCTTGGCTGCAAAACACTTTATTGATGTAGGAGCTGGTGTCATAGATGAAGA                   TTATAGAGGAAATGTTGGTGTTGTACTGTTTAATTTTGGCAAAGAAAAGTTTGAAGTC                   AAAAAAGGTGATCGAATTGCACAGCTCATTTGCGAACGGATTTTTTATCCAGAAATAG                   AAGAAGTTCAAGCCTTGGATGACACCGAAAGGGGTTCAGGAGGTTTTGGTTCCACTGG                   AAAGAAT TAA   AATTTATGCCAAGAACAGAAAACAAGAAGTCATACCTTTTTCTTAAAA                       AAAAAAAAAAAGTTTTTGCTTCAAGTGTTTTGGTGTTTTGCACTTCTGTAAACTTACT                       AGCTTTACCTTCTAAAAGTACTGCATTTTTTACTTTTTTTTATGATCAAGGAAAAGAT                       CATTAAAAAAAAACACAAAGAAGTTTTTCTTTGTGTTTGGATCAAAAAGAAACTTTGT                       TTTTCCGCAATTGAAGGTTGTATGTAAATCTGCTTTGTGCTGACCTGATGTAAACAGT                       GTCTTCTTAAAATCAAATGTAAATCAATTCCCGATTAAAAAAAAAAGCCTGTATTTAA                       CTCAAAAAAAAA                                       ORF Start: ATG at 412   ORF Stop: TAA at 168           SEQ ID NO:8   252 aa MW at 26562.9 kD                     NOV3a,   MTPLCPRPALCYHFLTSLLRSAMQNARGARQRAEAAVLSGPGPPLGRAAQHGIPRPLS               CG134632-01   Protein SAGRLSQCCRGASTVGAAGWKGELPKAGGSPAPGPETPAISPSKRARPAEVCGMQLRF               Sequence   ARLSEHATAPTRCSARAACYDLYSAYDYTIPPMEKAVVKTDIQIALPSGCYGRVAPRS                   GLAAKHFIDVGAGVIDEDYRGNVGVVLFNFGKEKFEVKKGDRIAQLICERIFYPEIEE                   VQALDDTERGSGGFGSTGKN                                     SEQ ID NO:9   916 bp                     NOV3b,     GTTCCCACGACGGCCGCGTCTTCAGCCTCGAAGCCTGGCGCACGTCCGGAGGTGCCGA                 CG134632-02   DNA     GGACCCAACCAGCCCAAACTCTGGGAGAA   ATG ACTCCCCTCTGCCCTCGCCCCGCGCT               Sequence   CTGCTACCATTTCCTTACGTCTCTGCTTCGCTCAGCGATGCAAAACGCGCGAGGCGCA                   CGGCAGAGGGCCGAAGCCGCGGTACTCTCCGGGCCAGGCCCGCCCCTCGGCCGCGCCG                   CGCAGCACGGGATTCCCCGGCCGCTGTCCAGCGCTGGCCGCCTGAGCCAAGGCTGCCG                   CGGAGCCAAGACACCCGCCATTTCACCCAGTAAGCGGGCCCGGCCTGCGGAGGTGGGC                   GGCATGCAGCTCCGCTTTGCCCGGCTCTCCGAGCACGCCACGGCCCCCACCCGGGGCT                   CCGCGCGCGCCGCGGGCTACGACCTGTACAGTGCCTATCATTACACAATACCACCTAT                   GGAGAAAGCTGTTGTGAAAACGGACATTCAGATAGCGCTCCCTTCTGGGTGTTATGGA                   AGAGTGGCTCCACGGTCAGGCTTGGCTCCAAAACACTTTATTGATCTAGGAGCTGGTG                   TCATAGATGAAGATTATAGAGGAAATCTTCGTCTTGTACTGTTTAATTTTGGCAAAGA                   AAAGTTTGAAGTCAAAAAACGTGATCGAATTGCACAGCTCATTTGCGAACGGATTTTT                   TATCCAGAAATAGAACAAGTTCAAGCCTTGGATGACACCGAAAGGGGTTCAGGAGGTT                   TTGGTTCCACTGGAAAGAAT TAA   AATTTATGCCAAGAACAGAAAACAAGAAGTCATAC                       CTTTTTCTTAAAAAAAAAAAAAGTTTTTGCTTCAAGTGTTTTGGTGTTTTGCACTTCT                       GTAAACTTACTAGCTTTACCTTCTAAAAGTACTGCATTTTTTACTT                                       ORF Start: ATG at 88   ORF Stop: TAA at 775           SEQ ID NO: 10   229 aa MW at 24487.7 kD                     NOV3b,   MTPLCPRPALCYHFLTSLLRSANQNARGARQRAEAAVLSGPGPPLGRAAQHGIPRPLS               CG134632-02 Protein   SAGRLSQGCRGAKTPAISPSKRARPAEVGGMQLRFARLSEHATAPTRGSARAAGYDLY               Sequence   SAYDYTIPPMEKAVVKTDIQIALPSGCYGRVAPRSGLAAKHFIDVGAGVIDEDYRGNV                   GVVLFNFGKEKFEVKKGDRIAQLICERIFYPEIEEVQALDDTERGSGGFGSTGKN                  
 
     [0274] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 3B.  
               TABLE 3B                          Comparison of NOV3a against NOV3b.                                 NOV3a Residues/   Identities/Similarities           Protein Sequence   Match Residues   for the Matched Region                                     NOV3b   1 . . . 252   228/252   (90%)           1 . . . 229   229/252   (90%)                  
 
     [0275] Further analysis of the NOV3a protein yielded the following properties shown in Table 3C.  
               TABLE 3C                       Protein Sequence Properties NOV3a                                        PSort   0.4632 probability located in mitochondrial matrix space;       analysis:   0.3000 probability located in microbody (peroxisome); 0.2322           probability located in lysosome (lumen); 0.1612 probability           located in mitochondrial inner membrane       SignalP   Cleavage site between residues 29 and 30       analysis:                  
 
     [0276] A search of the NOV3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3D.  
               TABLE 3D                          Geneseq Results for NOV3a                                         NOV3a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value                                             AAW30281   Human dUTPase (mitochondrial form) -   1 . . . 252   235/252   (93%)    e−134             Homo sapiens , 252 aa. [WO9736916-A1,   1 . . . 252   236/252   (93%)           09 OCT. 1997]       AAW30280   Human dUTPase (nuclear form) -  Homo     94 . . . 252   159/159   (100%)   3e−88             sapiens , 164 aa. [WO9736916-A1, 09   6 . . . 164   159/159   (100%)           OCT. 1997]       AAR70144   Human dUTPase protomer -  Homo     112 . . . 252   141/141   (100%)   2e−77             sapiens , 141 aa. [CA2126001-A, 28   1 . . . 141   141/141   (100%)           JAN. 1995]       ABB60791   Drosophila melanogaster polypeptide   104 . . . 250   96/147   (65%)   1e−50           SEQ ID NO 9165 - Drosophila   12 . . . 158   114/147   (77%)           melanogaster, 188 aa. [WO200171042-           A2, 27 SEP. 2001]       AAB44003   Human cancer associated protein   94 . . . 185   91/92   (98%)   2e−46           sequence SEQ ID NO:1448 -  Homo     12 . . . 103   91/92   (98%)             sapiens , 106 aa. [WO200055350-A1, 21           SEP. 2000]                  
 
     [0277] In a BLAST search of public sequence datbases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3E.  
               TABLE 3E                          Public BLASTP Results for NOV3a                                         NOV3a   Identities/           Protein       Residues/   Similarities for           Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                             P33316   Deoxyuridine 5′-triphosphate   1 . . . 252   235/252   (93%)    e−134           nucleotidohydrolase, mitochondrial   1 . . . 252   236/252   (93%)           precursor (EC 3.6.1.23) (dUTPase) (dUTP           pyrophosphatase) -  Homo sapiens             (Human), 252 aa.       Q96Q81   DUTP PYROPHOSPHATASE -  Homo     94 . . . 252   159/159   (100%)   8e−88             sapiens  (Human), 164 aa.   6 . . . 164   159/159   (100%)       A46256   dUTP pyrophosphatase (EC 3.6.1.23) -   112 . . . 252   141/141   (100%)   4e−77           human, 141 aa.   1 . . . 141   141/141   (100%)       Q9CU90   5133400F09RIK PROTEIN -  Mus     31 . . . 252   154/222   (69%)   3e−76             musculus  (Mouse), 204 aa (fragment).   3 . . . 204   167/222   (74%)       Q8VCG1   SIMILAR TO DUTPASE -  Mus musculus     30 . . . 252   154/225   (68%)   9e−75           (Mouse), 200 aa.   9 . . . 200   167/225   (73%)                  
 
     [0278] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3F.  
               TABLE 3F                          Domain Analysis of NOV3a                                     Identities/                   Similarities                   for the   Expect       Pfam Domain   NOV3a Match Region   Matched Region   Value                                         dUTPase   121 . . . 250   71/138   (51%)   1.1e−64               123/138   (89%)                  
 
     Example 4  
     [0279] 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:11   814 bp                     NOV4a,     GACTCTCCGCACTATCCTTACCCGTGACAGCCACTGACGTCCTCCGCCCCTAGAAGAG                 CG139186-01 DNA     ACCCCGCTTCTCGGCGCCTGCCCTCCCCCTCGCGGCTCGGTCCCGCCCCGCCAGCACC                 Sequence     GCTACCTCCGCCAGCCTCGCCACCATCAGCACCACCTCCACCGCCGCCGCCGCCGCCA                       CCACCACCGCCGCCGGCCGCAGCAGCCATTTCATCTCCACAGACCAGACACAAAAA                       C   ATG GCAGAAATGGAGAAAGAAGGGAGACCTCCCGAAAATAAACGGAGCAGGAAGCCG                   GCTCACCCAGTGAAAAGGGAGATCAATGAGGAGATGAAGAACTTTGCAGAAAACACCA                   TGAATGAACTCCTTGCCTGGTATGGCTATGATAAGGTTGAATTAAAAGATGGTGAGGA                   TATTGAATTCAGGAGCTACCCTACAGATCGCGAGAGCCGGCAGCACATTTCTGTTCTC                   AAAGAAAATTCTTTGCCAAAACCAAAATTACCCGAGGACAGTGTTATTTCACCATACA                   ATATAAGCACAGGCTATTCACGCCTTGCCACTGGAAATGGACTCAGTGACTCACCTGC                   AGGGTCAAAGGATCATGGCAGTGTGCCCATTATTGTACCTTTAATTCCACCACCTTTC                   ATAAAGCCACCAGCAGAAGATGATGTGTCAAATGTACAAATAATGTGTGCCTGGTGCC                   AGAAAGTGGGAATCAAGCGCTATTCCCTGAGTATGGGAAGTGAGGTGAAAAGCTTC TA                       G AGCCACAACTGCTTTGACGCCTTCCCACCGGCCTCACTCAAAAGAAATATGGCTAAT                         CA                                       ORF Start: ATG at 234   ORF Stop: TAG at 753           SEQ ID NO:12   173 aa MW at 19250.6 kD                     NOV4a,   MAEMEKEGRPPENKRSRKPAHPVKREINEEMKNFAENTMNELLGWYGYDKVELKDGED               CG139186-01 Protein   IEFRSYPTDGESRQHISVLKENSLPKPKLPEDSVISPYNISTGYSGLATGNGLSDSPA               Sequence   GSKDHGSVPIIVPLIPPPFTKPPAEDDVSNVQIMCAWCQKVGIKRYSLSMGSEVKSF                  
 
     [0280] Further analysis of the NOV4a protein yielded the following properties shown in Table 4B.  
               TABLE 4B                       Protein Sequence Properties NOV4a                                        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:                  
 
     [0281] A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4C.  
               TABLE 4C                          Geneseq Results for NOV4a                                         NOV4a   Identities/                   Residues/   Similarities for           Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value                                             ABG01994   Novel human diagnostic protein #1985 -   1 . . . 141   140/141   (99%)   1e−79             Homo sapiens , 182aa. [WO200175067-   1 . . . 141   141/141   (99%)           A2, 11 OCT. 2001]       ABG01994   Novel human diagnostic protein #1985 -   1 . . . 141   140/141   (99%)   1e−79             Homo sapiens , 182 aa. [WO200175067-   1 . . . 141   141/141   (99%)           A2, 11 OCT. 2001]       ABG27565   Novel human diagnostic protein #27556 -   10 . . . 140   115/132   (87%)   5e−62             Homo sapiens , 791 aa.   64 . . . 195   119/132   (90%)           [WO200175067-A2, 11 OCT. 2001]       ABG02501   Novel human diagnostic protein #2492 -   10 . . . 140   115/132   (87%)   5e−62             Homo sapiens , 791 aa. [WO200175067-   64 . . . 195   119/132   (90%)           A2, 11 OCT. 2001]       ABG27565   Novel human diagnostic protein #27556 -   10 . . . 140   115/132   (87%)   5e−62             Homo sapiens , 791 aa.   64 . . . 195   119/132   (90%)           [WO200175067-A2, 11 OCT. 2001]                  
 
     [0282] 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 4D.  
               TABLE 4D                          Public BLASTP Results for NOV4a                                         NOV4a   Identities/           Protein       Residues/   Similarities for           Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                             Q95TY2   GH22790P - Drosophila melanogaster   23 . . . 53   18/32   (56%)   8e−04           (Fruit fly), 813 aa.   65 . . . 96   28/32   (87%)       Q9V620   CG8991 PROTEIN - Drosophila   23 . . . 53   18/32   (56%)   8e−04           melanogaster (Fruit fly), 774 aa.   26 . . . 57   28/32   (87%)       AAM07637   CONSERVED HYPOTHETICAL   59 . . . 119   20/61   (32%)   1.9           PROTEIN - Methanosarcina   193 . . . 253   28/61   (45%)           acetivorans str. C2A, 375 aa.       AAM03932   CELL SURFACE PROTEIN -   59 . . . 117   18/59   (30%)   1.9           Methanosarcina acetivorans str. C2A,   738 . . . 796   28/59   (46%)           923 aa.       Q9JL19   PPAR INTERACTING PROTEIN   12 . . . 145   38/143   (26%)   3.3           PRIP -  Mus musculus  (Mouse), 2067   1461 . . . 1592   59/143   (40%)           aa.                  
 
     [0283] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4E.  
               TABLE 4E                       Domain Analysis of NOV4a                                                        Identities/           Pfam       Similarities   Expect       Domain   NOV4a Match Region   for the Matched Region   Value                  
 
     Example 5  
     [0284] 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   1108 bp                     NOV5a,     CTTCGTCCACCGCCTCCCGACC   ATG GACCCCCACAAAGTGAATCCACTTCGGGCTTTT               CG94620-01 DNA       GTGAAAATGTGTAAGCAGGATCTGAGCGTTCTGCACACCAAGGAAATGCACTTCCTGA               Sequence   GGGAGTGGGTGGAGAGCATGGGGGGTAAACTATCACCTGCTACTCAGAAAGTTAAATC                   AGAAGAAAATACCAAGGAAGAAAAACCTGATAGTAAGAAGGTGGAGGAAGACTTAAAG                   CCAGACGAACCATCAAGTGAGGAAAGTAATCTATTAATTGATAATCAAGGTGTGATTG                   AACCAGACCCTGATGCCCCTCAAGAAATGGGAGATGAAAATGCAGAGATAACAGAGGA                   GATGATGGATCAGGCAAATCATAAGAAAGTGGCTCCTATTGAAGCCCTAAATGATGGT                   GAACTGCAGAAAGCCATTGACTTATTCACAGATGCCATCAAGCTGAATCCTCAGTTGG                   CCATTTTGTATGCCAAGAGGGCCAGTGTCTTCATCAAATTACAGAAGCCAAATGCTGC                   CATCCGAGACTGTGACAGAGCCGTTGAAATAAATCCTGATTCAGCTCAGCCTTACAAG                   TGGCGAGGTAAAGCACACAGACTTCTAGGCCACTGGGAAGGAGCAGCCCATGATCTTG                   CCCTTGCCTGTAAATTGGATTATGATGAAGATGCTAGTGCAATGCTCAAACAAGTTCA                   GCCTAGGGCACAGACAATTGCGGAACATCAGAGAAAGTATGAGCAAAAACGTGAAGAG                   CGAGAGATCAAAGAAAGAATAGAAAGAGTTAAGAAGGCTCGAGAAGACCAAGAGAGAG                   CCCAGAGGGAGGAAGAAGCCAGACGACAGTCAGTAGCTCAGTATGGCTCTTTTCCAGA                   TGGACTTCCTGGGGGAATGCTTGGAATGAGAGGGGGCATGCCTGGGATGGCCGGAATA                   ACTGCACTCAATGAAATTCTTAGTGATCCAGAGATTCTTGCAGCCGTGCAGGATCCCA                   AAGTTATGGTGGCCTTCCAGGATGTCGCTCAAAACCCAGCAAATATGTCACAATACCA                   GGGCAACCCAAAGGTTATGAATCTTATCAGTAAATTGTCAGCCAAATTTGGAGGTCAA                   GAG TAA                                       ORF Start: ATG at 23   ORF Stop: TAA at 1106           SEQ ID NO:14   361 aa MW at 40495.4 kD                     NOV5a,   MDPHKVNALRAFVKMCKQDLSVLHTKEMHFLREWVESMGGKLSPATQKVKSEENTKEE               CG94620-01 Protein   KPDSKKVEEDLKADEPSSEESNLLIDNEGVIEPDPDAPQEMGDENAEITEEMMDQANH               Sequence   KKVAAIEALNDGELQKAIDLFTDAIKLNPQLAILYAKRASVFIKLQKPNAAIRDCDRA                   VEINPDSAQPYKWRGKAHRLLGHWEGAAHDLALACKLDYDEDASAMLKEVQPRAQTIA                   EHQRKYEQKREEREIKERIERVKKAREEQERAQREEEARRQSVAQYGSFPDGLPGGML                   GMRGGMPGMAGITGLNEILSDPEILAAVQDPKVMVAFQDVAQNPANMSQYQGNPKVMN                   LISKLSAKFGGQE                  
 
     [0285] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B.  
               TABLE 5B                       Protein Sequence Properties NOV5a                                        PSort   0.7600 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:                  
 
     [0286] 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                                             ABG13621   Novel human diagnostic protein #13612 -   1 . . . 360   327/368   (88%)   0.0             Homo sapiens , 369 aa. [WO200175067-   1 . . . 368   340/368   (91%)           A2, 11 OCT. 2001]       ABG13621   Novel human diagnostic protein #13612 -   1 . . . 360   327/368   (88%)   0.0             Homo sapiens , 369 aa. [WO200175067-   1 . . . 368   340/368   (91%)           A2, 11 OCT. 2001]       AAY07080   Renal cancer associated antigen precursor   1 . . . 360   324/368   (88%)   0.0           sequence -  Homo sapiens , 369 aa.   1 . . . 368   339/368   (92%)           [WO9904265-A2, 28 JAN. 1999]       AAY16629   Protein encoded by the novel gene   1 . . . 360   324/368   (88%)   0.0           HSU17714 -  Homo sapiens , 369 aa.   1 . . . 368   339/368   (92%)           [WO9931228-A1, 24 JUN. 1999]       ABG11507   Novel human diagnostic protein #11498 -   1 . . . 360   323/368   (87%)   0.0             Homo sapiens , 379 aa. [WO200175067-   11 . . . 378   338/368   (91%)           A2, 11 OCT. 2001]                  
 
     [0287] In a BLAST search of public sequence datbases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 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                                             P50502   Hsc70-interacting protein (Hip) (Putative   1 . . . 360   327/368   (88%)   0.0           tumor suppressor ST13) (Progesterone   1 . . . 368   340/368   (91%)           receptor-associated p48 protein) -  Homo               sapiens  (Human), 369 aa.       Q99L47   SIMILAR TO SUPPRESSION OF   1 . . . 360   310/371   (83%)    e−174           TUMORIGENICITY 13 (COLON   1 . . . 370   332/371   (88%)           CARCINOMA) (HSP70-INTERACTING           PROTEIN) -  Mus musculus  (Mouse), 371           aa.       P50503   Hsc70-interacting protein (Hip) (Putative   1 . . . 359   303/367   (82%)    e−172           tumor suppressor ST13)-  Rattus     1 . . . 366   329/367   (89%)             norvegicus  (Rat), 368 aa.       O45786   T12D8.8 PROTEIN - Caenorhabditis   6 . . . 359   169/375   (45%)   2e−78           elegans, 422 aa.   4 . . . 374   231/375   (61%)       O49648   HSP ASSOCIATED PROTEIN LIKE-   53 . . . 361   151/332   (45%)   4e−72           Arabidopsis thaliana (Mouse−ear cress),   303 . . . 627   214/332   (63%)           627 aa.                  
 
     [0288] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5E.  
               TABLE 5E                          Domain Analysis of NOV5a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV5a Match Region   for the Matched Region   Value                                         TPR   148 . . . 181   11/34   (32%)   3.8e−05               27/34   (79%)                  
 
     Example 6  
     [0289] 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   4690 bp                     NOV6a,     TTGGCCGCC   ATG GAGTATTGTTTACACCCGGAGCCGCAGTCTCAGCATGAACTTGGGA               CG94882-01 DNA       ATGTTTTCTTIAAAATTCAAGGACAAGTTCTGCGTGTACGAGGAGTATTGCAGCAACCA               Sequence   TGAGAAAGCCCTGAGGCTGCTGGTGGAGCTGAACAAGATCCCTACCGTGCGCGCCTTC                   CTTTTGAGCTGCATGCTTCTGGGAGGCCGGAAGACCACGGACATCCCTTTGGAAGGCT                   ACCTGTTGTCTCCGATCCACAGGATCTGCAAGTACCCGCTCCTCCTTAAGGAGCTGGC                   CAAGAGGACTCCCGCCAAGCACCCAGACCACCCCGCCGTCCAGAGTGCCCTGCAGGCC                   ATGAAGACCGTTTGCTCCAACATCAATGAGACCAAGCGGCAGATGGAGAAGCTGGAAG                   CCCTGGAGCAGCTGCAGTCCCACATCGAAGGCTGCCAGGGTTCCAACCTCACAGACAT                   CTGCACTCAGCTCCTCCTGCAAGGGACTTTGTTAAAGATCTCTGCGGGCAACATCCAG                   GAAAGGGCCTTCTTCCTCTTCGACAACCTTCTCGTCTACTGCAAGCGGAAATCCAGGG                   TCACCGGGAGCAAGAAGTCCACCAAGAGGACCAAATCCATCAACGGCTCCCTCTACAT                   CTTCAGGGGTCGAATCAACACTGAAGTCATGGAGGTGGAGAATGTGGAACATGGGACA                   GCGGATTACCATACCAACCGCTATACCGTCACCAACGGCTGGAAGATCCACAACACGG                   CCAAGAATAAGTGGTTTGTCTGCATGGCCAAGACGGCAGAGGAGAAGCAGAAGTGGCT                   GGATGCCATCATCCGCGAGCGGGAGCAGCGCGAGAGCCTGAAGCTGGGCATGGAGCGT                   GATGCCTACGTCATGATTGCGGAGAAGGGGCAGAACCTGTACCACATGATGATGAACA                   AGAAGGTGAACCTCATCAAGGACCGCCGGAGAAAGCTGAGCACTGTCCCCAAGTGCTT                   TCTTGGCAATGAGTTCGTTGCCTGGCTCCTAGAAATTGGTGAAATCAGCAAGACGGAA                   GAAGGAGTCAACTTGGGCCAAGCCCTGTTGGAGAATGGCATCATCCACCATGTTTCCG                   ACAAGCACCAGTTCAAGAATGACCAGGTGATGTATCGCTTCCCCTACCACGATGGCAC                   CTACAAGGCCCGAAGTGAGCTGGAGGACATCATGTCCAAGGGTGTGAGGCTTTACTGC                   CGTCTTCACAGCCTCTACACCCCGGTGATCAAAGACCGTGATTACCACCTGAAGACCT                   ACAAGTCAGTGCTTCCCGGGAGCAAGCTGGTGGACTGGCTGCTGGCTCAGGGAGACTG                   CCAGACTCGGGAGGAGGCAGTGGCGCTCGGCGTGGGTCTGTGCAACAATGGCTTCATG                   CACCACGTGCTGGAGAAGACCGAGTTCACGGATGAGTCCCAGTACTTCCCCTTTCATG                   CTGACGAGGAGATGGAGGGGACCAGCAGCAAGAACAAACAGCTTCGCAACGACTTCAA                   GCTGGTGGAGAACATTCTGGCCAAGCGCCTGCTGATCCTGCCCCAGGAGGAGGACTAT                   GGCTTTGACATCGAGGAGAAGAACAAGGCTGTCGTCGTGAAGTCCGTCCAGAGGGGCT                   CGCTGGCTGAGGTGGCTGGCCTGCAGGTGGGGAGGAAGATCTACTCCATCAATGAGGA                   CCTGGTGTTCCTGCGGCCGTTTTCAGAGGTGGAGTCCATCCTCAACCAGTCCTTCTGC                   TCCCGCCGCCCTCTGCCCCTCCTGGTGCCCACGAAGGCCAAAGAGATCATCAAAATCC                   CCGACCAGCCGGACACACTGTGCTTCCAGATTCGTGGAGCTGCCCCACCGTACGTCTA                   TGCTGTGGGGAGAGGCTCTGAGGCCATGGCTGCAGGGCTCTGTGCTGGTCAGTGCATT                   CTGAAGGTCAATGGCAGCAACGTGATGAACGATGGTGCCCCTGAGGTCCTGGAGCACT                   TCCAGGCATTCCGGAGTCGGCGCGAAGAGGCCCTGGGCCTGTACCAGTGGATCTACCA                   CACCCATGAGGATGCCCAGGAAGCACGAGCCAGTCAGGAGGCCTCCACTGAGGACCCC                   AGTGGCGAGCAGGCCCAGGAGGAAGACCAGGCTGATTCAGCCTTCCCACTGCTGTCCC                   TGGGTCCCCGGCTGAGCCTGTGTGAGGACAGCCCCATGGTCACCCTGACTGTGGACAA                   CGTGCACCTCGAACACCGCGTGCTGTATCACTATGTGAGCACGGCAGGCGTCAGGTGC                   CATGTGCTGGAGAAGATCCTGGAGCCCCGCGGCTGCTTCGGCCTCACCGCCAAGATCC                   TCGAGGCCTTTGCTGCCAATGACAGCGTCTTCGTGGAGAACTGCAGGCGGCTCATGGC                   CCTGAGCAGCGCCATCGTGACCATCCCCCACTTTGAGTTCCGCAACATCTGTGACACC                   AAGCTGGAGAGCATTGGCCAGAGGATTGCCTGCTACCAGGAGTTTGCAGCCCAACTGA                   AGAGCAGGGTCAGCCCACCCTTCAAACAAGCCCCCCTGGAGCCCCACCCGCTGTGTGG                   CCTGGACTTCTGCCCCACCAATTGCCACATCAACCTCATGGAAGTGTCCTACCCCAAG                   ACCACCCCCTCAGTGGGCAGGTCCTTCAGCATCCGCTTTGGACGCAAACCCTCCCTCA                   TCGGCCTTGACCCGGAGCAAGGCCACCTGAACCCCATGTCGTACACCCAGCACTGCAT                   CACCACCATGGCTCCTCCCTCCTGGAAGTGCTTGCCTGCTGCAGAGGGTGATCCCCAA                   GGCCAGGGTCTCCATGATGGCAGCTTCGGGCCAGCCAGTGGGACCCTTGGTCAGGAAG                   ACCGGGCCCTCAGCTTCCTACTCAAGCAGGAGGACCGTGAGATCCAGGATGCCTACCT                   GCAGCTCTTCACCAAGCTCGATGTGGCCCTGAAGGAGATGAAGCAATATGTCACCCAG                   ATCAACAGGCTGCTGTCCACCATCACAGAGCCCACCTCGGGTGGGTCCTGCGACGCAT                   CCTTGGCTGAGGAGGCCTCCTCCCTGCCCCTGGTCAGTGAAGAGAGCGAGATGGACAG                   GAGTGACCATGGGGGCATCAAGAAGGTGTGCTTCAAGGTGGCCGAGGAGGACCAGGAG                   GACTCAGGCCACGACACCATGAGTTATCGCGACTCCTACAGCGAGTGTAACAGCAATC                   GAGACTCGGTCCTGTCCTACACCAGCGTGAGAAGTAACAGCTCCTACTTGGGCAGCGA                   CGAGATGGGGTCTGGAGATGAGCTGCCCTGTGACATGcGGATCCCATCTGACAAGCAG                   GACAAGCTTCATGGCTGCCTGGAGCACCTCTTTAACCAGGTGGACTCCATCAATGCTC                   TCCTCAAGGGGCCAGTCATGAGCCGGGCTTTCGAAGAGACCAA3CATTTCCCTATGAA                   CCACAGCTTACAAGAGTTTAAACAGAAAGAAGAGTGTACAATCCGTGGCCGGAGCCTG                   ATCCAGATTAGCATCCAGGAGGACCCCTGGAACCTCCCCAACTCCATCAAGACCCTGG                   TGGACAACATTCAGAGATATGTGGAAGATGGGAAGAACCAGCTGCTCCTCGCCTTGCT                   GAAGTGCACAGACACGGAGCTGCAGCTGCGCAGAGACGCGATCTTCTGCCAGGCCCTG                   GTGGCCGCCGTGTGCACCTTCTCCGAGCAGCTGCTGGCGGCCCTGGGCTACCGCTACA                   ACAACAATGGCCAGTACGAGCAGAGCACCCGCGACCCCAGCCGCAAGTGGCTGGAGCA                   GGTGGCGCCCACGGGCGTCCTGCTGCACTGCCAGTCCCTCCTCTCGCCAGCCACAGTG                   AAGGAGGAACGGACCATGCTGGAGGACATCTGGGTGACGCTGTCAGAGCTGGACAATG                   TCACCTTCTCCTTTAAGCAGCTGGACGAGAACTATGTGGCCAACACCAACGTCTTCTA                   CCACATTGAGGGCAGCCGGCAGGCGCTGAAGGTCATCTTCTACCTCGACAGCTACCAC                   TTCTCCAAGCTGCCCTCCCGCCTGGAGGGTGGGGCCAGCCTGAGGCTGCACACAGCGC                   TGTTCACGAAAGTGCTGGAGAACGTGGAGGGGCTGCCTTCTCCAGGCAGCCAGGCCGC                   GGACGATTTCCAGCAGGACATCAACCCGCAGTCCCTGGAGAAAGTTCAGCAGTATTAC                   CGCAAACTCAGGGCATTTTACCTGGACCGGTCTAACCTGCCCACGGATGCCAGCACCA                   CGGCGGTAAAGATAGACCAGCTGATCCGCCCCATCAATGCCCTGGATGAGCTCTGCCG                   CCTCATGAAGTCCTTTGTCCACCCAAAGCCTGGTGCTGCTGGGAGTGTGGGCGCCGGC                   CTCATCCCCATCTCCTCGGAGCTCTGCTACCGCCTGGGGGCCTGCCAGATCGTCATGT                   GTGGCACAGGCATGCAGAGGAGCACCCTGAGCGTGTCCCTGGAGCAGGCGGCCATCTT                   GGCACGGAGCCACGGGTTGCTGCCCAAGTGCATCATGCAGGCCACGGACATCATGCGG                   AAOCAGGGCCCAAGGGTGGAGATTCTGGCCAAAAACCTGCGAGTCAAGGACCAGATGC                   CCCAGGGTGCTCCGCGCCTCTACCGCCTCTGCCAGCCGCCGGTGGATGGGGACCTC TG                       A   ACACCCAAATGCCCCACGCTGGGCCGCGGCCTCTGGAGCTGGGATTTGG                                       ORF Start: ATG at 10   ORF Stop: TGA at 4639           SEQ ID NO:16   1543 aa MW at 173855.5 kD                     NOV6a,   MEYCLHPEPQSQHELGNVFLKFKDKFCVYEEYCSNHEKALRLLVELNKIPTVRAFLLS               CG94882-01 Protein   CMLLGGRKTTDIPLEGYLLSPIQRICKYPLLLKELAKRTPGKHPDHPAVQSALQAMKT               Sequence   VCSNINETKRQMEKLEALEQLQSHIEGWEGSNLTDICTQLLLQGTLLKISAGNIQERA                   FFLFDNLLVYCKRKSRVTGSKKSTKRTKSINGSLYIFRGRINTEVMEVENVEDGTADY                   HSNGYTVTNGWKIHNTAKNKWFVCMAKTAEEKQKWLDAIIREREQRESLKLGMERDAY                   VMIAEKGEKLYHMMMNKKVNLIKDRRRKLSTVPKCFLGNEFVAWLLEIGEISKTEEGV                   NLGQALLENGIIHHVSDKHQFKNEQVMYRFRYDDGTYKARSELEDIMSKGVRLYCRLH                   SLYTPVIKDRDYHLKTYKSVLPGSKLVDWLLAQGDCQTREEAVALGVGLCNNGFMHHV                   LEKSEFRDESQYFRFHADEEMEGTSSKNKQLRNDFKLVENILAKRLLILPQEEDYGFD                   LEEKNKAVXTVKSVQRGSLAEVAGLQVGRKIYSINEDLVFLRPFSEVESILNQSFCSRR                   PLRLLVATKAKEIIKIPDQPDTLCFQIRGAAPPYVYAVGRGSEAMAAGLCAGQCILKV                   NGSNVMNDGAPEVLEHFQAFRSRREEALGLYQWIYHTHEDAQEARASQEASTEDPSGE                   QAQEEDQADSAFPLLSLGPRLSLCEDSPMVTLTVDNVHLEHGVVYEYVSTAGVRCHVL                   EKIVEPRGCFGLTAKILEAFAANDSVFVENCRRLMALSSAIVTMPHFEFRNICDTKLE                   SIGQRIACYQEFAAQLKSRVSPPFKQAPLEPHPLCGLDFCPTNCHINLMEVSYPKTTP                   SVGRSFSIRFGRKPSLIGLDPEQGHLNPMSYTQHCITTMAAPSWKCLPAAEGDPQGQG                   LHDGSFGPASGTLGQEDRGLSFLLKQEDREIQDAYLQLFTKLDVALKEMKQYVTQINR                   LLSTITEPTSGGSCDASLAEEASSLPLVSEESEMDRSDHGGIKKVCFKVAEEDQEDSG                   HDTMSYRDSYSECNSNRDSVLSYTSVRSNSSYLGSDEMGSGDELPCDMRIPSDKQDKL                   HGCLEHLFNQVDSINALLKGPVMSRAFEETKHFPMNHSLQEFKQKEECTIRGRSLIQI                   SIQEDPWNLPNSIKTLVDNIQRYVEDGKNQLLLALLKCTDTELQLRRDAIFCQALVAA                   VCTFSEQLLAALGYRYNNNGEYEESSRDASRKWLEQVAATGVLLHCQSLLSPATVKEE                   RTMLEDIWVTLSELDNVTFSFKQLDENYVANTNVFYHIEGSRQALKVIFYLDSYHFSK                   LPSRLEGGASLRLHTALFTKVLENVEGLPSPGSQAAEDLQQDINAQSLEKVQQYYRKL                   RAFYLERSNLPTDASTTAVKIDQLIRPINALDELCRLMKSFVHPKPGAAGSVGAGLIP                   ISSELCYRLGACQMVMCGTGMQRSTLSvSLEQAAILARSHGLLPKCIMQATDIMRKQG                   PRVEILAKNLRVKDQMPQGAPRLYRLCQPPVDGDL                  
 
     [0290] Further analysis of the NOV6a protein yielded the following properties shown in Table 6B.  
               TABLE 6B                       Protein Sequence Properties NOV6a                                        PSort   0.9400 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:                  
 
     [0291] 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 [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value                                             AAM38941   Human polypeptide SEQ ID NO 2086 -   591 . . . 1543   951/953   (99%)   0.0             Homo sapiens , 956 aa. [WO200153312-   4 . . . 956   953/953   (99%)           A1, 26 JUL. 2001]       AAU21633   Novel human neoplastic disease   1 . . . 427   426/427   (99%)   0.0           associated polypeptide #66 -  Homo     77 . . . 503   427/427   (99%)             sapiens , 503 aa. [WO200155163-A1, 02           AUG. 2001]       AAB94398   Human protein sequence SEQ ID   128 . . . 826   419/700   (59%)   0.0           NO:14968 -  Homo sapiens , 762 aa.   1 . . . 691   538/700   (76%)           [EP1074617-A2, 07 FEB. 2001]       AAM40727   Human polypeptide SEQ ID NO 5658 -   1162 . . . 1543   379/382   (99%)   0.0             Homo sapiens , 398 aa. [WO200153312-   17 . . . 398   381/382   (99%)           A1, 26 JUL. 2001]       AAB95639   Human protein sequence SEQ ID   485 . . . 1076   275/600   (45%)   e−137           NO:18376 -  Homo sapiens , 577 aa.   1 . . . 564   379/600   (62%)           [EP1074617-A2, 07 FEB. 2001]                  
 
     [0292] 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                                             CAC86401   P-REX1 PROTEIN -  Homo sapiens     1 . . . 1543   1541/1543   (99%)   0.0           (Human), 1659 aa.   117 . . . 1659   1542/1543   (99%)       Q9P2D2   KIAA1415 PROTEIN -  Homo sapiens     5 . . . 1543   1538/1539   (99%)   0.0           (Human), 1539 aa (fragment).   1 . . . 1539   1538/1539   (99%)       Q9UGQ4   DJ998C11.1 (KIAA1415 PROTEIN   1 . . . 985   984/985   (99%)   0.0           (CONTAINS A RHOGEF DOMAIN)) -   44 . . . 1028   985/985   (99%)             Homo sapiens  (Human), 1028 aa           (fragment).       Q9BQH0   HYPOTHETICAL 106.1 KDA   591 . . . 1543   950/953   (99%)   0.0           PROTEIN -  Homo sapiens  (Human),   4 . . . 956   952/953   (99%)           956 aa.       Q9H4Q6   BA269H4.1 (KIAA1415 PROTEIN) -   987 . . . 1543   556/557   (99%)   0.0             Homo sapiens  (Human), 557 aa   1 . . . 557   557/557   (99%)           (fragment).                  
 
     [0293] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6E.  
               TABLE 6E                          Domain Analysis of NOV6a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV6a Match Region   for the Matched Region   Value                                         RhoGEF   2 . . . 123   51/207   (25%)   0.00087               88/207   (43%)       PH   156 . . . 276   26/121   (21%)   1.6e−10               91/121   (75%)       DEP   305 . . . 380   22/89   (25%)   1.7e−10               54/89   (61%)       DEP   407 . . . 481   21/89   (24%)   4.7e−05               52/89   (5 8%)       PDZ   509 . . . 589   19/86   (22%)   0.041                57/86   (66%)                  
 
     Example 7  
     [0294] 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   4619 bp                     NOV7a,     TCTCTCATACAAGGGAAGTGGGGCAGTACGAAGGAACTGGAG   ATG GGAAAAGCATGGG               CG94915-01 DNA   GCTGGCTCTTCCCCGCCGAGGTTGGTGGATCATTTGAGGGCAGGAGTTTGACACCAGC               Sequence   CTGGCCAACATGGCGAAACCCTGCCTCTCAGCTACTTGGGAGGCTGAGGCAGGAGAAT                   CGCTTGAACCTGGCAGGTGCAGGCGAAGCCAAGATCGGTCGCGCCCGTCCCCCTTCTC                   CCCGCCCACCTCGAGCCTGCAGGAGACGGGACCCCGAGGGCCCACAGGCACCGGACCT                   ACTCACCCGGCAGGCCGCTCTCCTCGGTGCAGACAGCACAGGGAGGAGGGGGAAGCGG                   CTCTGCCGGGAACAGGGAGGGACCTCCAGGGAAGCGAAACTGAAACTTTGCGCCCAGT                   CCCCCCGGCCACCTCCGCTACAGCAGCCGCCGAAGCTGAACCCGGGGTGTGGAGGTTG                   TAGTGACCCCCCCCCCCCCCCACTCAAGGGCTCTGTGAGTTCTCAGGCCTCACAACTC                   GACAAGAAGGAAAAGGGCATCTGTGTCATCTGTATGGACACCATTAGTAACAAAAAAG                   TGCTACCAAAGTGCAAGCATGAATTCTGCGCCCCTTGTATCAACAAAGCCATGTCATA                   TAAGCCAATCTGTCCCACATGCCAGACTTCCTATGGTATTCAGAAAGGAAATCAGCCA                   GAGGGAAGCATGGTTTTCACTGTTTCAAGAGACTCACTTCCAGGTTATGAGTCCTTTG                   GCACCATTGTGATTACTTATTCTATGAAACCACGCATACAAACACAGGAAGAACACCC                   AAACCCAGGAAAGAGATACCCTGGAATACAGCGAACTGCATACTTGCcTGATAATAAG                   GAAGGAAGGAAGGTTTTCAAACTGCTTTATAGGGCCTTTGACCAAAAGCTGATTTTTA                   CAGTGGGGTACTCTCGCGTATTAGGAGTCTCAGATGTCATCACTTGGAATGATATTcA                   CCACAAAACATCCCGGTTTGGAGGACCAGAAATGTATGCCTATCCTGATCCTTCTTAC                   CTGAAACGTGTCAAAGAGGAGCTCAAAGCCAAAGGAATTGAGGAAGACAACTGCTGCA                   AGATGTCT TAA   ATCAAGCTTTCAAAAAATATATTTTAGGAGGCTGATTTAATGCCAG                       TCTAAATCCTTATCTACAAAGGACTTTGAAATTTTTCTTCTCAAGAAATGGTTTGTAT                       AAGAATAACAATCTGCTAGTCTGTCATTTCTGGAGTGATACTTTTTTTTTTGAGACGG                       AGTCTCCTCTGTCGCTCGCGCTGGAGTGCAGTGGCATGATCTCGCCTCACTGCAAGCT                       CCGCCTCCCAGGTTCATGCCATTCTCCTACCTCAGCCTCCCGAGTAGCTGGGACTACA                       GGCGCCCACCACCATGCCCGGCTAATTTTTGTTTTTGTATTTTTAGTAGAGACAGGGT                       TTCACTGTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCAG                       CCTTCCAAAGTGTTGGGATTATAGGCGTGAGCCACCGCCCCCAGCCCTGGAGTGATAC                       TTTTTATGGAAGACAAAAGCCCCCCAAATCTGTGTAAAATCTGCTGCAAAGGTGTCAT                       CCCTCTTGTGTCATCACTGGGGTTAGAGGTGGCTCCCAAATAATCTTCTGTGTCCTTC                       AGTTGGACTCTCGGCTGCCAATTGATCTCTTTTTCATTGCCATCTCTGGCCTGGTTCT                       TTGGTTTTTTGTGTGTTTTCCCCTTCATCTCTACCTGTGAAAGTGAAATTCTATTGTA                       AATGGGAGGAAAAAGGGTTGGTTGTGAAAAATTAAAGACCCACATTCTGCTTTCTTAC                       TCATGGTAAGAAAAGTGGCCATGAGTAGAGATTGGGCAAGCATTGGTAATAAATGGAA                       TAAGACTATTATTATTATTATTTGAGATGCAGTCTCACTCTGTCACCCAGGCTGGAAT                       GCAGTGGTGTGATCTTCCCTCACTGCAACCTCCACTTCCCGGGTTCAAGCGATTCTCC                       TGCCTCAGCCTCCTGAGTAGCTGGGATTACAGGTGTGTGCCTCCACACCCGGCTAATT                       TTTTGTATTTTTAGTAGAGACGGGGTTTTGCCATGTTGGCCAGGCTGGTTTCAAACTC                       CTGAGCTCAAATGATCCTCCTGCCTTGGCCTCCCAAAGTGCTGGAATTACAGGCATGA                       GCCACCACACCCACACAAGACTATCATTTTTAATGACCAAGAGCCTAGTATATAGTTG                       GTGCCTGTCTTACTCTGTTTGTGTTCCTATAAAAGAACACCTGAGACTGGGTAATTGA                       TAAAGAAAAAGGTTTGTTTGGCTCACAATTTTGCTGGCTAGAAGGTTGGGCATCCGGT                       GAAAGCCTCAGGCTGCTTCCATTCATAGCAAAGGGCAGCCAGTGTGTGCAGAAATCAA                       ATGACAGAGAGGAAGTGAGAGAGAGACGTGTCGGGGAGGTGCCAGGCTCTTTTTAACA                       AGCAGTTCTTCAGGAACTAAGAGTGAGTCACTCCCATGAGAACAGCACCAAGCCATTC                       ATGGGGGAATCTCCCCCCATGACCCAGACCCCTCCCGTTAGGCTTCACCTCCAACACT                       GAGGATCAAATTTCAACATGAGATTTGGAGCAGGTCAAACAAACTAAACTGTAGCAGT                       GTTTCATAAAATTGTTTt~CCTGACTCAGGTTGCTAGTAAGCCAGCAGAGGGATATTTG                       CCTCCTAAATCTTTGGCAGAGGCAGGAGTAAGGAAGCCATTTCTGGAGTCCTTGCTAC                       TAATTTGGAAAACTGAGCTTCTTTCTTTCATTGCTTTTTCCCTTAAGAGACAAGTCCT                       TACTATATTGCCCTGTCTCTCAAGGGAAGACATCAAGACTGGACTTGAACTCCTGGGC                       TCAAGCCATCCCCCAACCTTGGCCTCTCGAGTAGATGGCATTATAGGCATGTGCCACG                       GTGCCTGACTTGAGTTTCTTATTCTAGAACACTTGGAGCCTGAACTCTGACCAGGCCC                       CTCACTTGAGCCTTTGCTTTCTGCTCCTTGTAAACTGCCATATTGGGTGCACTTGCCC                       TGCCACAGTAATGCTATATATTTCTGAGCATTGTTTTTCTCTAGATAATTTTATATTT                       TTGAGTATACCCCACTTCCAAGTGTTTTTTGTTTTGTTTTGCTTTGTTTTTGTTGTTG                       TTGTTTTGAGACAGGGTCTCACTGTGTCCCCCAGGCTGGAGTGCAGTGGCACAATGAC                       GACTCACTGCAGCCTCAACCTCCTGGGGCCAAGTGATCCACCCACCTCAGCCTCCCAA                       GTAGCTGGGACCACAGGCACAGTGCCACCACGCCCATGCCTAAAGCATTTTTTTTTTT                       TTTTTTGGTCGAGATGGGGTGTCCCTGTGTTGCCCAGACTGGTCTTGCCCTCCTCGAC                       TCAAGGCATCCTCCTGTCTTGGGCTCCCAAAGTCTTGGGATTACAGGCGTGAGTGACC                       ATGCCTAGCTCACTTCCAGGTTTAACAGACAAAATAAACTTACTCTAGTTTCCATCTC                       TATCATTTTATAATAACCGTAGCCCACATTGTAGTAGTTTTTCACCTCTTTACTAAGT                       CCCACCAATTCATGTTTTCACCCTTAAAATCTTTCTCACTGATACTCTCTCTGGACAG                       AAAAAAGGTGAAATAAGCCTACTATAAGGAATATATGACATGCTAAATTTTATTTTTA                       AACGGTTCTTCAAGTCAGATTAAAGTAATAATAGCAAATTATGTGATTATCCATGTCC                       CAGCCTCTCTCCAAAAAAATAGTAAACAAGATGTCTTCTTCTTTTCCCAAAGATACAC                       ATACACACATGTACAATTTTTTTATCACATAATAATAGCTAATATTTAATGAGTACT                       TACCTTAGTTTGTCCCCTTTACAACAGCTTTACATCTGTGTCGATTGATACAGTTCAT                       ATTCCCATTTTATAACTGAGGAAAACTGGGTGCACAGAGGAGGATAAGCAACTTGCCA                       AACGTCACACACTTAATAAGTGGAAATGCTGGGGTATGAACCAGGTAGTCTGCCCCCA                       TAGCTCTGCCCCCCAGACCTGTACTGTCTCCCATGAGGGTACTTCTCCATGGAGCAGC                       CTGAGGCGATCCCTTTATTCTGGGCTTCTCTCAGAAATGGATTCCCACACAGTATTCA                       AAGCAAATTTCCCCAGAGGAAATCCTATTGGAAGAACTTAAAAACTCAGAATCTTTTT                       CTTTGTCCAGAGAGTTGAGGAAGCTTAAGCTAAATGATACATGTTTTTAAAAAAAAAT                       CAGATTATAAATTTAGTTTTTGGTGATTCATTAAATTCTTTACTATTATAGTTATTTT                       CTAGCTGTTCATCTTTTAGCTAAATTTGTTCCAAACAACCAAAAGTTTGGTTTCTACT                       AAGTTCTGGATTCTGGATGGGAGATTGCACTGTGTGTGACATGCAAGTTTCATGGTGT                       GGGAGATTGCAGAGCATTTGGGTTACTGCTTTTACTCTTTGGAACCTGTTATCATCTG                       AAAAAAAGTTTTGCCTATAGTAGTCGTATTCAATTTC                                       ORF Start: ATG at 43   ORF Stop: TAA at 1111           SEQ ID NO:18   1356 aa MW at 39166.6 kD                     NOV7a,   MGKAWGWLFPAEVCGSFEGRSLRPAWPTWGNPASQLLGRLRQENRLNLGGGGEAKIGR               CG94915-01 Protein   ARPPSPRPPRACRRGDPEGPEAPDLLTRQAALLGADSTGRRGKRLCREQGGTSREAKL               Sequence   KLCAQSPRPPPLQQPPKLNPGCCGCSDPPPPPLKGSVSSEASELDKKEKGICVICMDT                   ISNKKVLPKCKHEFCAPCINKAmSYKPICPTCQTSYGIQKGNQPEGSMVFTVSRDSLP                   GYESFGTIVITYSMKAGIQTQEEHPNPGKRYPGIQRTAYLPDNKEGRKVLKLLYRAFD                   QKLIFTVGYSRVLGVSDVITWNDIHHKTSRFGCPEMYGYPDPSYLKRVKEELKAKGIE                   EDNCWKMS                  
 
     [0295] Further analysis of the NOV7a protein yielded the following properties shown in Table 7B.  
               TABLE 7B                       Protein Sequence Properties NOV7a                                        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:                  
 
     [0296] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7C.  
               TABLE 7C                          Geneseq Results for NOV7a                                         NOV7a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value                                             AAM00777   Human bone marrow protein, SEQ ID   147 . . . 326   178/180   (98%)    e−102           NO:140 -  Homo sapiens , 603 aa.   425 . . . 603   178/180   (98%)           [WO200153453-A2, 26 JUL. 2001]       AAM00890   Human bone marrow protein, SEQ ID   147 . . . 277   130/131   (99%)   9e−73           NO:366 - Homo sapiens, 212 aa.   83 . . . 212   130/131   (99%)           [WO200153453-A2, 26 JUL. 2001]       ABB50177   Human transcription factor TRFX-28 -   23 . . . 350   144/339   (42%)   6e−66             Homo sapiens , 347 aa. [WO200172777-   23 . . . 347   185/339   (54%)           A2, 04 OCT. 2001]       AAM84104   Human immune/haematopoietic antigen   249 . . . 349   95/101   (94%)   2e−50           SEQ ID NO:11697 -  Homo sapiens , 116   1 . . . 100   97/101   (95%)           aa. [WO200157182-A2, 09 AUG. 2001]       AAB95594   Human protein sequence SEQ ID   140 . . . 350   97/237   (40%)   8e−40           NO:18275 -  Homo sapiens , 622 aa.   384 . . . 617   130/237   (53%)           [EP1074617-A2, 07 FEB. 2001]                  
 
     [0297] In a BLAST search of public sequence datbases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7D.  
               TABLE 7D                          Public BLASTP Results for NOV7a                                         NOV7a   Identities/           Protein       Residues/   Similarities for           Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                             AAL90859   RHYSIN 2 -  Homo sapiens  (Human), 740   147 . . . 348   201/202   (99%)    e−116           aa.   540 . . . 740   201/202   (99%)       Q9ER06   DELTEX3 -  Mus musculus  (Mouse), 347   11 . . . 350   150/353   (42%)   1e−66           aa.   9 . . . 347   192/353   (53%)       Q9H890   CDNA FLJ13862 FIS, CLONE   140 . . . 350   97/237   (40%)   2e−39           THYRO1001120, MODERATELY   384 . . . 617   130/237   (53%)           SIMILAR TO  HOMO SAPIENS  DELTEX           (DX) MRNA -  Homo sapiens  (Human),           622 aa.       Q96H69   UNKNOWN (PROTEIN FOR   145 . . . 350   96/232   (41%)   8e−39           MGC:14983) -  Homo sapiens  (Human),   389 . . . 617   128/232   (54%)           622 aa.       Q9P200   KIAA1528 PROTEIN -  Homo sapiens     145 . . . 350   96/232   (41%)   8e−39           (Human), 740 aa (fragment).   507 . . . 735   128/232   (54%)                  
 
     [0298] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7E.  
               TABLE 7E                          Domain Analysis of NOV7a                                     Identities/           Pfam   NOV7a   Similarities       Domain   Match Region   for the Matched Region   Expect Value               zf-C3HC4   168 . . . 206   14/54 (26%)   4.2e−05               27/54 (50%)                  
 
     Example 8  
     [0299] 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:19   1321 bp                     NOV8a,     ACACTGCGTCCGGGGCCAGACGACGATATCAGCGCGGGGTCCCCACAACGCCATGGGG                 CG94966-01 DNA     CAGACCCAACTCTCGAGCGCGTGATCGAAGCCCGCAGTTTTTTCGCCCCCGTCACTTC                 Sequence     CGGGTGCGACAATCTCTTCTGTCCGGCCAGCCGCTGGAGTCGTTAGGTGCCGCCTTGC                       TTCTGACGAGCCACACGTTTGCTTCTTCCCTGTGTTCCCACCTGGAGGGAC   ATG AGTC                   TCCCTGGGCCGTCGTCTCCCGACGGGGCCCTGACACGGCCACCCTACTGCCTGGAGGC                   CGGGGAGCCGACGCCTGGTTTAAGTGACACTTCTCCAGATGAAGGGTTAATAGAGGAC                   TTGACTATAGAAGACAAAGCAGTGGAGCAACTGGCAGAAGGATTGCTTTCTCATTATT                   TGCCAGATCTGCAGAGATCAAAACAAGCCCTCCAGGAACTCACCAAGAACCAAGTTGT                   ATTGTTAGACACACTGGAACAAGAGATTTCAAAATTTAAAGAATGTCATTCTATGTTG                   GATATTAATGCTTTGTTTGCTGAGGCTAAACACTATCATGCCAAGTTGGTGAATATAA                   GAAAAGAGATGCTGATGCTTCATGAAAAAACATCAAAGTTAAAAAAAAGAGCACTTAA                   ACTGCAGCAGAAGAGGCAAAAAGAAGAGTTGGAAAGGGAGCAGCAACGAGAGAAGGAG                   TTTGAAAGAGAAAAGCAGTTAACTGCCAGACCAGCCAGGATG TGA   AAAGTTGTGT                       TTGTGTGTTTTCTTCTCCTGTCCCATATTTGGGTTATGATGACTCAAGTGTAGACTGA                       AGTTGAGGTAGTGCCTTATGCCATTATGTCATATGTTGAAATCCTTATTCCGCTATTA                       CTGTGTCTCCATGCCTTTTTTCCAAGTAGCAGACGTCATGTTGCATGGTTTTTGATAT                       TTATATGTAAGTTTTTCAAATTTTGCTTAATTTTAAAATTTATTATTTTGATCTTGAA                       TTATTTATAAACTGGAAAGTGGTTTGATTATTGTGAGTCAAAACTCTAAGTGGTTAAA                       AATTAGTATGAATTTTTTAGCTTCTTAATGAATATGGATTTAAAACTCTCCAGTTCTT                       ATTTTATGAAATGACTTGCCTTTCTGGTAATACAATGCTGATTTTTTAGTAATTGCCT                       TTTCATTACTTTGTTAAGAAGAAATGCCAGCTGTTTAATCACACCTACCCCTGGAAAA                       GAGGTAAACCTTTTGAACAGTTGAATTTCATCAGAAGCTCTATAGCTTTTTGGTCAGA                       GGAAGTGATACTCTTTATTACAAGAAACAAGGAATTAACAAAAAT                                       ORF Start: ATG at 226   ORF Stop: TGA at 742           SEQ ID NO:20   172 aa MW at 19743.4 kD                     NOV8a,   MSVPGPSSPDGALTRPPYCLEAGEPTPGLSDTSPDEGLIEDLTIEDKAVEQLAEGLLS               CG94966-01 Protein   HYLPDLQRSKQALQELTQNQVVLLDTLEQEISKFKECHSMLDINALFAEAKHYHAKLV               Sequence   NIRKEMLMLHEKTSKLKKRALKLQQKRQKEELEREQQREKEFEREKQLTARPAKRM                  
 
     [0300] Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.  
               TABLE 8B                       Protein Sequence Properties NOV8a                                        PSort   0.8200 probability located in 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:                  
 
     [0301] A search of the NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8C.  
               TABLE 8C                          Geneseq Results for NOV8a                                         NOV8a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               AAB43381   Human ORFX ORF3145 polypeptide    1 . . . 172   171/172 (99%)   2e−93           sequence SEQ ID NO: 6290 -  Homo      1 . . . 172   171/172 (99%)             sapiens , 172 aa. [WO200058473-A2, 05-OCT-2000]       AAG01196   Human secreted protein, SEQ ID NO:    1 . . . 112   112/112 (100%)   4e−60           5277 -  Homo sapiens , 112 aa.    1 . . . 112   112/112 (100%)           [EP1033401-A2, 06-SEP-2000]       ABB69026   Drosophila melanogaster polypeptide   48 . . . 155    36/111 (32%)   5e−07           SEQ ID NO: 33870 -  Drosophila      5 . . . 114    58/111 (51%)             melanogaster , 120 aa. [WO200171042-           A2, 27-SEP-2001]       ABG20431   Novel human diagnostic protein #20422 -   86 . . . 171    25/86 (29%)   0.002             Homo sapiens , 160 aa. [WO200175067-   39 . . . 121    47/86 (54%)           A2, 11-OCT-2001]       ABG20431   Novel human diagnostic protein #20422 -   86 . . . 171    25/86 (29%)   0.002             Homo sapiens , 160 aa. [WO200175067-   39 . . . 121    47/86 (54%)           A2, 11-OCT-2001]                  
 
     [0302] In a BLAST search of public sequence datbases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8D.  
               TABLE 8D                          Public BLASTP Results for NOV8a                                         NOV8a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9UL45   PALLID (PALLID (MOUSE)    1 . . . 172   172/172 (100%)   6e−94           HOMOLOG, PALLIDIN) -  Homo      1 . . . 172   172/172 (100%)             sapiens  (Human), 172 aa.       Q9R0C0   SYNTAXIN 13-INTERACTING    1 . . . 171   149/171 (87%)   4e−80           PROTEIN PALLID -  Mus musculus      1 . . . 171   156/171 (91%)           (Mouse), 172 aa.       Q91VG4   SIMILAR TO PALLIDIN -  Mus      1 . . . 75     57/75 (76%)   2e−25             musculus  (Mouse), 80 aa.    1 . . . 75     61/75 (81%)       Q9VTM0   CG14133 PROTEIN -  Drosophila      48 . . . 155    36/111 (32%)   1e−06             melanogaster  (Fruit fly), 120 aa.    5 . . . 114    58/111 (51%)       Q967H0   EEA1 -  Caenorhabditis elegans , 1205    38 . . . 162    33/125 (26%)   7e−04           aa.   479 . . . 603    60/125 (47%)                  
 
     [0303] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8E.  
               TABLE 8E                       Domain Analysis of NOV8a                                                Pfam Domain   NOV8a Match   Identities/Similarities   Expect Value           Region   for the               Matched Region                  
 
     Example 9  
     [0304] 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:21   553 bp                     NOV9a,     CGCTGACCCTGTCCGCCGCGCCCGGGGACGCGGGCGGAGGAGGCGCCGCGGCGGAGCC                 CG95053-01 DNA     CCCGGACGCGACC   ATG TCGGAGGTGCTGCCCTACGGCGACGAGAAGCTGAGCCCCTAC               Sequence   GGCGACGGCGGCGACCTCCGCCAGATCTTCTCCTGCCGCCTGCAGGACACCAACAACT                   TCTTCGGCGCCGGGCAGAACAAGCGGCCGCCCAAGCTGGGCCAGATCGGCCGGAGCAA                   GCGGGTTCTTATTGAAGATGATAGGATTGATGACGTGCTGAAAA-ATATGACCGACAAC                   GCACCTCCTGGTGTC TAA   CTCCCCCAAAGACAATGAGTTAACGCAGAGAATAACAACG                       GCGGTAACAGTTATTGGCAAAAAGCATGAAAAGAGAAAGCACTTTGAAATTTATTACT                       AGCTTGCTACCCACGATGAAATCAACAACCTGTATCTGGTATCAGGCCGGGAGACAGA                       TGAGGCGAGAGGACGAGGAGGAGGAGGAGAAGGCTCTGGGGCTCCTCTGCAAAAAAAA                       AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAT                                       ORF Start: ATG at 72   ORF Stop: TAA at 306           SEQ ID NO:22   78 aa MW at 8552.5 kD                     NOV9a,   MSEVLPYGDEKLSPYGDGGDVGQIFSCRLQDTNNFFGAGQNKRPPKLGQIGRsKRvvI               CG95053-01 Protein   EDDRIDDVLKND4TDKAPPGV       Sequence                  
 
     [0305] Further analysis of the NOV9a protein yielded the following properties shown in Table 9B.  
               TABLE 9B                       Protein Sequence Properties NOV9a                                        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:                  
 
     [0306] 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                                                    Geneseq   Protein/   NOV9a   Identities/   Expect       Identifier   Organism/Length   Residues/   Similarities for   Value           [Patent #, Date]   Match   the Matched               Residues   Region                  
 
     [0307] 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               Q9JI15   CAM-KINASE II INHIBITOR ALPHA -    1 . . . 78   76/78 (97%)   1e−39             Rattus norvegicus  (Rat), 78 aa.    1 . . . 78   77/78 (98%)       Q9Z2N6   CAM-KII INHIBITORY PROTEIN    1 . . . 78   54/81 (66%)   5e−24           (2900075A18RIK PROTEIN) -  Rattus      1 . . . 79   64/81 (78%)             norvegicus  (Rat), and, 79 aa.       Q96S95   CAM-KII INHIBITORY PROTEIN -    1 . . . 78   53/81 (65%)   3e−23             Homo sapiens  (Human), 79 aa.    1 . . . 79   63/81 (77%)       O32756   Phosphoglycerate kinase (EC 2.7.2.3) -   19 . . . 61   17/43 (39%)   1.4             Lactobacillus delbrueckii  (subsp.   110 . . . 152   24/43 (55%)           bulgaricus), 403 aa.                  
 
     [0308] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9E.  
               TABLE 9E                       Domain Analysis of NOV9a                                                Pfam Domain   NOV9a   Identities/   Expect Value           Match Region   Similarities for               the Matched Region                  
 
     Example 10  
     [0309] 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:23   536 bp                     NOV10a,     CGTGGCAGGCTCCCTGGGTACCGGCTGTCGCTGACCCAGGAGAAGCTGCCTGTCTACA                 CG95063-01 DNA     TCAGCCTGGGCTGCAGCGCGCTGCCGCCGCGGGGCCGGCAGCC   ATG GCCAAGGACATC               Sequence   CTGGGTGAGCAGGGCTACACTTTGATGAACTGAACAAGCTGAGGGTGTTGGACCCAG                   AGGTTACCCAGCAGACCATAGAGCTGAAGGAAGAGTGCAAAGACTTTGTGGACAAAAT                   TGGCCAGTTTCAGAAAATAGTTGGTGGTTTAATTGAGCTTGTTGATCAACTTGCAAAA                   GAAGCAGAAAATGAAAAGATGAAGGCCATCGGTGCTCGGAACTTGCTCAAATCTATAG                   CAAAGCAGAGAGAAGCTCAACAGCAGCAACTTCAAGCCCTAATAGCAGAAAAGAAAAT                   GCAGCTAGAAAGGTATCGGGTTGAATATGAAGCTTTGTGTAAAGTAGAAGCACAACAA                   AATGAATTTATTGACCAATTTATTTTTCAGAAATGAAC TGA   ACTGAAAATNTCGCTTTTATAG                       TAGGAAGGCAAAAC                                       ORF Start: ATG at 102   ORF Stop: TGA at 498           SEQ ID NO:24   132 aa MW at 15280.5 kD                     NOV10a,   MAKDILCEAGLHFDELNKLRVLDPEVTQQTIELKEECKDFVDKIGQFQKIVGGLIELV               CG95063-01 Protein   DQLAKEAENEKMKAIGARNLLKSIAKQREAQQQQLQALIAEKKMQLERYRVEYEALCK               Sequence   VEAEQNEFIDQFIFQK                  
 
     [0310] Further analysis of the NOV10a protein yielded the following properties shown in Table 10B.  
               TABLE 10B                       Protein Sequence Properties NOV10a                                        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:                  
 
     [0311] A search of the NOV10a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10C.  
               TABLE 10C                          Geneseq Results for NOV10a                                         NOV10a   Identities/                   Residues/   Similarities for           Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               AAU81505   Human interflagellar transport protein,    1 . . . 132   132/132 (100%)   5e−69           IFT20 #1 -  Homo sapiens , 132 aa.    1 . . . 132   132/132 (100%)           [WO200190307-A2, 29-NOV-2001]       AAU27978   Human contig polypeptide sequence    1 . . . 132   132/132 (100%)   5e−69           #131 -  Homo sapiens , 171 aa.   40 . . . 171   132/132 (100%)           [WO200164834-A2, 07-SEP-2001]       AAU27806   Human full-length polypeptide sequence    1 . . . 132   132/132 (100%)   5e−69           #131 -  Homo sapiens , 132 aa.    1 . . . 132   132/132 (100%)           [WO200164834-A2, 07-SEP-2001]       AAW74836   Human secreted protein encoded by gene    1 . . . 132   132/132 (100%)   5e−69           108 clone HEBEK93 -  Homo sapiens ,   27 . . . 158   132/132 (100%)           159 aa. [WO9839448-A2, 11-SEP-1998]       AAG03068   Human secreted protein, SEQ ID NO:   1 . . . 75    75/75 (100%)   3e−36           7149 -  Homo sapiens , 75 aa.   1 . . . 75    75/75 (100%)           [EP1033401-A2, 06-SEP-2000]                  
 
     [0312] In a BLAST search of public sequence datbases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10D.  
               TABLE 10D                          Public BLASTP Results for NOV10a                                         NOV10a   Identities/           Protein       Residues/   Similarities for           Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q61025   HYPOTHETICAL 15.2 KDA   1 . . . 132   130/132 (98%)   7e−68           PROTEIN (0610009H04RIK   1 . . . 132   131/132 (98%)           PROTEIN) -  Mus musculus  (Mouse),           132 aa.       Q90WZ0   INTRAFLAGELLAR TRANSPORT   1 . . . 132   114/132 (86%)   2e−60           PROTEIN 20 -  Xenopus laevis  (African   1 . . . 132   124/132 (93%)           clawed frog), 132 aa.       Q99M35   SIMILAR TO UTERINE PROTEIN -    1 . . . 106   104/106 (98%)   7e−52             Mus musculus  (Mouse), 106 aa.   1 . . . 106   105/106 (98%)       Q9BUG5   SIMILAR TO UTERINE PROTEIN -    1 . . . 73     71/73 (97%)   4e−34             Homo sapiens  (Human), 148 aa.   1 . . . 73     73/73 (99%)       AAL77186   HYPOTHETICAL 14.9 KDA   1 . . . 125    45/128 (35%)   4e−15           PROTEIN -  Caenorhabditis elegans , 129   1 . . . 123    75/128 (58%)           aa.                  
 
     [0313] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10E.  
               TABLE 10E                       Domain Analysis of NOV10a                                                Pfam   NOV10a Match   Identities/   Expect Value       Domain   Region   Similarities for the               Matched Region                  
 
     Example 11  
     [0314] 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:25   472 bp                     NOV11a,     GGTC   ATG GAGGGAGCAGGAGCTGGATCAGGCTTCCCGAAGGAGCTGGTGAGCAGGCTG               CG95072-01 DNA   CTGCACCTGCACTTCAAGGATGACAAGACCAAAGTGAGCGGGGACGCGCTGCAGCTCA               Sequence   TGGTGGAGTTGCTGAAGGTCTTCGTTGTGGAAGCAGCAGTCCGCGGCGTGCGGCAGGC                   CCAGGCAGAAGACGCGCTCCGTGTGGACGTGGACCAGCTGGAGAAGGTGCTTCCGCAG                   CTGCTCCTGGACTTC TAG   GGATCTCAGCCGTGGCTGAGGCCACCCCCAGAGGAGCCCC                       TGGTCCACAGAAGCAGGCCTTGTGTTTCCAGCGGCCTCTGATAAGAGGCAGGGAAGGA                       CCTGAAGGATTTGGAGTTGATTCAAACAAGATCTCTGGGAGTCTCCCTGCCTCTCCTC                       CCTGGGACAATAGTGTGTTTGACAAACAGCAGCTGGCAGCGCTGCCTCCTGCCCACAT                       TCCTGCCA                                       ORF Start: ATG at 5   ORF Stop: TAG at 248           SEQ ID NO:26   81 aa MW at 8959.3 kD                     NOV11a,   MEGAGAGSGFRKELVSRLLHLHFKDDKTKVSGDALQLMVELLKVFVVEAAVRGVRQAQ               CG95072-01 Protein   AEDALRVDVDQLEKVLPQLLLDF       Sequence                  
 
     [0315] Further analysis of the NOV11a protein yielded the following properties shown in Table 11B.  
               TABLE 11B                       Protein Sequence Properties NOV11a                                        PSort   0.4500 probability located in cytoplasm;       analysis:   0.3167 probability located in microbody (peroxisome);           0.1507 probability located in lysosome (lumen);           0.1000 probability located in mitochondrial matrix space       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0316] A search of the NOV11 a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 11C.  
               TABLE 11C                          Geneseq Results for NOV11a                                             Identities/                   NOV11a   Similarities                   Residues/   for the           Geneseq   Protein/Organism/Length [Patent #,   Match   Matched   Expect       Identifier   Date]   Residues   Region   Value               AAG89185   Human secreted protein, SEQ ID NO: 305 -     1 . . . 81   81/81 (100%)   7e−39             Homo sapiens , 81 aa. [WO200142451-A2,    1 . . . 81   81/81 (100%)           14-JUN-2001]       AAG73701   Human colon cancer antigen protein SEQ    1 . . . 74   74/74 (100%)   1e−34           ID NO: 4465 -  Homo sapiens , 197 aa.   10 . . . 83   74/74 (100%)           [WO200122920-A2, 05-APR-2001]       AAB58866   Breast and ovarian cancer associated    1 . . . 74   74/74 (100%)   1e−34           antigen protein sequence SEQ ID 574 -    10 . . . 83   74/74 (100%)             Homo sapiens , 197 aa. [WO200055173-           A1, 21-SEP-2000]       ABB63329     Drosophila melanogaster  polypeptide SEQ    9 . . . 73   23/68 (33%)    0.25           ID NO 16779 -  Drosophila melanogaster ,   815 . . . 876   34/68 (49%)            1417 aa. [WO200171042-A2, 27-SEP-2001]       AAB03063   Maize KIN17 orthologue, ZmKINH-1 -    46 . . . 77   12/32 (37%)    3.7             Zea mays , 424 aa. [WO200024900-A1, 04-MAY-2000]   338 . . . 369   21/32 (65%)                   
 
     [0317] 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               O08694   D9 SPLICE VARIANT 2 -  Mus      1 . . . 81   62/81 (76%)   2e−25             musculus  (Mouse), 78 aa.    1 . . . 78   68/81 (83%)       O00281   D9 SPLICE VARIANT A -  Homo      1 . . . 81   62/81 (76%)   4e−25             sapiens  (Human), 63 aa.    1 . . . 63   63/81 (77%)       Q96DD4   SIMILAR TO STIMULATED BY    1 . . . 81   62/81 (76%)   5e−25           RETINOIC ACID 13 -  Homo sapiens      1 . . . 63   62/81 (76%)           (Human), 63 aa.       O08695   D9 SPLICE VARIANT 3 -  Mus     13 . . . 81   57/69 (82%)   3e−24             musculus  (Mouse), 169 aa.   101 . . . 169   62/69 (89%)       O08693   D9 SPLICE VARIANT 1 -  Mus     13 . . . 81   57/69 (82%)   3e−24             musculus  (Mouse), 111 aa.    43 . . . 111   62/69 (89%)                  
 
     [0318] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11E.  
               TABLE 11E                       Domain Analysis of NOV11a                                                Pfam Domain   NOV11a Match   Identities/   Expect Value           Region   Similarities for the               Matched Region                  
 
     Example 12  
     [0319] The NOV12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12A.  
               TABLE 12A                       NOV12 Sequence Analysis                                                SEQ ID NO:27   412 bp                     NOV12a,     ATCTTTGCCTCTTTGGAGTAGGAAATTCAGACTTGAAAAAGTGGTGTGTGGTTGACTC                 CG95217-01 DNA     TGTTTCTCGCC   ATG TCTTCTCACAAGACTTTCACCATTAAGCGATTCCTGGCCAAGAA               Sequence   ACAAAAGCAAAATCGTCCCATCCCCCAGTGGATTCAGATGAAACCTGGTAGTAAAATC                   AGGTACAACTCCAAAAGGAGGCATTGGAGAAGAACCAAGCTCCGTCTATAAGGAATTG                     CACATGAGATGGCACACATATTTATGCTGTATCAAGTTCACGATCATCTTACGATATC                       AAGCTGAAAATGTCACCACTACCTGGACAGTTGCACATGTTTTACTGGGAATATTTTT                       TTTCTGTTTTTCTGTATGCTCTGTGCTAGTAGGGTGGATTCAGTAATAAATATGTGAA                       AGCTTT                                       ORF Start: ATG at 70   ORF Stop: TAA at 223           SEQ ID NO:28   51 aa MW at 6292.5 kD                     NOV12a,   MSSHKTFTIKRFLAKKQKQNRPIPQWIQMKPGSKIRYNSKRRHWRRTKLGL       CG95217-01 Protein       Sequence                  
 
     [0320] Further analysis of the NOV12a protein yielded the following properties shown in Table 12B.  
               TABLE 12B                       Protein Sequence Properties NOV12a                                        PSort   0.8400 probability located in nucleus; 0.7500 probability       analysis:   located in mitochondrial intermembrane space;           0.6400 probability located in microbody (peroxisome);           0.3600 probability located in mitochondrial matrix space       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0321] 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                                             Identities/                   NOV12a   Similarities                   Residues/   for the           Geneseq   Protein/Organism/Length [Patent #,   Match   Matched   Expect       Identifier   Date]   Residues   Region   Value               AAE13838   Human lung tumor-specific protein L39 -     1 . . . 51   47/51 (92%)   2e−22             Homo sapiens , 51 aa. [WO200172295-A2,    1 . . . 51   49/51 (95%)           04-OCT-2001]       AAE13838   Human lung tumor-specific protein L39 -     1 . . . 51   47/51 (92%)   2e−22             Homo sapiens , 51 aa. [WO200172295-A2,    1 . . . 51   49/51 (95%)           04-OCT-2001]       AAB43896   Human cancer associated protein sequence    1 . . . 51   47/51 (92%)   2e−22           SEQ ID NO: 1341 -  Homo sapiens , 72 aa.   22 . . . 72   49/51 (95%)           [WO200055350-A1, 21-SEP-2000]       AAB53693   Human colon cancer antigen protein    1 . . . 51   47/51 (92%)   2e−22           sequence SEQ ID NO: 1233 -  Homo     30 . . . 80   49/51 (95%)             sapiens , 80 aa. [WO200055351-A1, 21-SEP-2000]       AAG35356     Zea mays  protein fragment SEQ ID NO:    1 . . . 50   36/50 (72%)   4e−16           43178 -  Zea mays  subsp. mays, 51 aa.    1 . . . 50   42/50 (84%)           [EP1033405-A2, 06-SEP-2000]                  
 
     [0322] 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               Q96EH5   SIMILAR TO RIBOSOMAL PROTEIN   1 . . . 51   51/51 (100%)   1e−24           L39 -  Homo sapiens  (Human), 51 aa.   1 . . . 51   51/51 (100%)       CAC44158   PUTATIVE RIBOSOMAL PROTEIN   1 . . . 51   47/51 (92%)    4e−22           L39 PROTEIN -  Oncorhynchus mykiss     1 . . . 51   49/51 (95%)            (Rainbow trout) (Salmo gairdneri), 51 aa.       Q98TF5   RIBOSOMAL PROTEIN L39 -  Gallus     1 . . . 51   47/51 (92%)    4e−22             gallus  (Chicken), 51 aa.   1 . . . 51   49/51 (95%)        Q90YS9   RIBOSOMAL PROTEIN L39 -  Ictalurus     1 . . . 51   46/51 (90%)    9e−22             punctatus  (Channel catfish), 51 aa.   1 . . . 51   49/51 (95%)        Q9CQD0   4930517K11RIK PROTEIN -  Mus     1 . . . 51   46/51 (90%)    1e−21             musculus  (Mouse), 51 aa.   1 . . . 51   48/51 (93%)                   
 
     [0323] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12E.  
               TABLE 12E                          Domain Analysis of NOV12a                                 NOV12a    Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               Ribosomal_L39   9 . . . 51   25/43 (58%)   4.5e−23               40/43 (93%)                  
 
     Example 13  
     [0324] The NOV13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13A.  
               TABLE 13A                       NOV13 Sequence Analysis                                                SEQ ID NO:29   509 bp                     NOV13a,     ATG GCCTTGGCCGGGGCCGCTGGGGTCTGGACGGGGGTCGCCATGATCCGCTTTATCC               CG95261-01 DNA   TCATCCAGAACCGGGCAGGCAAGACGCGCCTGGCCCACCGGTTCATGCAGTTTGATGA               Sequence   TGATGAGAAACAGAAGCTGATCGAGGAGGTGCATGCCGTGGTCACCGTCCGAGACGCC                   AAACACACCAACTTTGTGGAGTTCCGGAACTTTAAGATCATTTACCGCCGCTATGCTG                   GCCTCTACTTCTGCATCTGTGTGGATGTCAATGACAACAACCTGGCTTACCTGGAGGC                   CATTCACAACTTCGTGGAGGTCTTAAACGAATATTTCCACAATGTCTGTGAACTGGAC                   CTGGTGTTCAACTTCTACAAGGTTTACACGGTCGTGGACGACATGTTCCTGGCTGGCG                   AAATCCGAGAGACCAGCCAGACGAAGGTGCTGAAACAGCTGCTGATGCTACAGTCCCT                   GGAG TGA   GGGCAGGCGAGCCCCACCCCGGCCCCGGCCAAGGCCAT                                       ORF Start: ATG at 1   ORF Stop: TGA at 469           SEQ ID NO:30   156 aa MW at 18228.0 kD                     NOV13a,   MALAGAAGVWTGVAMIRFILIQNRAGKTRLAQRFMQFDDDEKQKLIEEVHAVVTVRDA               CG95261-01 Protein   KHTNFVEFRNFKIIYRRYAGLYFCICVDVNDNNLAYLEAIHNFVEVLNEYFHNVCELD               Sequence   LVFNFYKVYTVVDEMFLAGEIRETSQTKVLKQLLMLQSLE                  
 
     [0325] Further analysis of the NOV13a protein yielded the following properties shown in Table 13B.  
               TABLE 13B                       Protein Sequence Properties NOV13a                                                PSort   0.8264 probability located in mitochondrial           analysis:   intermembrane space;               0.5992 probability located in mitochondrial               matrix space;               0.3721 probability located in microbody (peroxisome);               0.3057 probability located in mitochondrial               inner membrane           SignalP   Cleavage site between residues 27 and 28           analysis:                      
 
     [0326] 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                                 Geneseq   Protein/Organism/Length   NOV13a Residues/   Identities/Similarities           Identifier   [Patent #, Date]   Match Residues   for the Matched Region   Expect Value               AAO13498   Human polypeptide SEQ ID NO 27390 -   5 . . . 156   149/152 (98%)   2e−82             Homo sapiens , 170 aa. [WO200164835-   19 . . . 170   151/152 (99%)           A2, 07-SEP-2001]       ABG25383   Novel human diagnostic protein #25374 -   5 . . . 148   141/158 (89%)   2e−75             Homo sapiens , 174 aa.   17 . . . 174   143/158 (90%)           [WO200175067-A2, 11-OCT-2001]       ABG24012   Novel human diagnostic protein #24003 -   5 . . . 148   141/158 (89%)   2e−75             Homo sapiens , 174 aa.   17 . . . 174   143/158 (90%)           [WO200175067-A2, 11-OCT-2001]       ABG25383   Novel human diagnostic protein #25374 -   5 . . . 148   141/158 (89%)   2e−75             Homo sapiens , 174 aa.   17 . . . 174   143/158 (90%)           [WO200175067-A2, 11-OCT-2001]       ABG24012   Novel human diagnostic protein #24003 -   5 . . . 148   141/158 (89%)   2e−75             Homo sapiens , 174 aa.   17 . . . 174   143/158 (90%)           [WO200175067-A2, 11-OCT-2001]                  
 
     [0327] 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                                 Protein                       Accession       NOV13a Residues/   Identities/Similarities       Number   Protein/Organism/Length   Match Residues   for the Matched Portion   Expect Value               Q00380   Clathrin coat assembly protein AP17   15 . . . 156   139/142 (97%)   9e−76           (Clathrin coat associated protein AP17)   1 . . . 142   141/142 (98%)           (Plasma membrane adaptor AP-2 17 kDa           protein) (HA2 17 kDa subunit) (Clathrin           assembly protein 2 small chain) -  Mus               musculus  (Mouse), and, 142 aa.       P53680   Clathrin coat assembly protein AP17   15 . . . 156   137/142 (96%)   1e−74           (Clathrin coat associated protein AP17)   1 . . . 142   139/142 (97%)           (Plasma membrane adaptor AP-2 17 kDa           protein) (HA2 17 kDa subunit) (Clathrin           assembly protein 2 small chain) -  Homo               sapiens  (Human), 142 aa.       Q9VDC3   CG6056 PROTEIN -  Drosophila     15 . . . 156   133/142 (93%)   8e−73             melanogaster  (Fruit fly), 142 aa.   1 . . . 142   137/142 (95%)       Q19123   HYPOTHETICAL 17.1 KDA PROTEIN -   15 . . . 156   132/142 (92%)   3e−72             Caenorhabditis elegans , 142 aa.   1 . . . 142   136/142 (94%)       Q9GQM7   ADAPTOR PROTEIN COMPLEX AP-2   15 . . . 156   129/142 (90%)   6e−70           SMALL CHAIN SIGMA2 -  Drosophila     1 . . . 142   135/142 (94%)             melanogaster  (Fruit fly), 142 aa.                  
 
     [0328] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13E.  
               TABLE 13E                          Domain Analysis of NOV13a                                 NOV13a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               Clat_adaptor_s   15 . . . 156   89/164 (54%)   2.5e−89               138/164 (84%)                  
 
     Example 14  
     [0329] 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:31   467 bp                      NOV14a,     CGGCAGGCCCTCTTCGGCAGTCTCTCCGGCCCGGTTTCCCTCGGCGTGCTACTGTGCG                 CG95292-01 DNA     CTCGATCCAGCACC   ATG GGGAAGCGGGACAATCGGGTGGCCTATATGAACCCAATAGC               Sequence   AATGGCGAGATCAAGGGGTCCAATCCAGTCTTCAGGGCCAACAATACAGGATTATCTG                   AATCGACCAAGGCCTACCTGGGAAGAAGTAAAAGAGCAACTAGAAAAGAAAAAGAAAG                   GCTCCAAGGCTTTGGCTGAATTTGAAGAAAAAATGAATGAGAACTGGAAGAAAGAACT                   GGAAAAACACAGGGAGAAATTGTTAAGTGGAAGTGAGAGCTCATCCAAAAAAAGACAG                   AGAAAGAAAAAAGAAAAGAAGAAATCTGGTAGGTATTCATCTTCTTCTTCATCAAGCT                   CTGATTCTCCAGCAGTCTTC TGA   TCTGAAGATAGGATAGAAACAAGAAAACGGAAAGA                       AAA                                       ORF Start: ATG at 73   ORF Stop: TGA at 427           SEQ ID NO:32   118 aa MW at 13592.3 kD                     NOV14a,   MGKRDNRVAYMNPIAMARSRGPIQSSGPTIQDYLNRPRPTWEEVKEQLEKKKKGSKAL               CG95292-01 Protein   AEFEEKMNENWKKELEKHREKLLSGSESSSKKRQRKKKEKKKSGRYSSSSSSSSDSPA               Sequence   VF                  
 
     [0330] Further analysis of the NOV14a protein yielded the following properties shown in Table 14B.  
               TABLE 14B                       Protein Sequence Properties NOV14a                                                PSort   0.9571 probability located in nucleus;           analysis:   0.4977 probability located in mitochondrial               matrix space;               0.2152 probability located in mitochondrial               inner membrane;               0.2152 probability located in mitochondrial               intermembrane space           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0331] A search of the NOV14a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14C.  
               TABLE 14C                          Geneseq Results for NOV14a                                 Geneseq   Protein/Organism/Length   NOV14a Residues/   Identities/Similarities           Identifier   [Patent #, Date]   Match Residues   for the Matched Region   Expect Value               AAU74347   Human cytoskeleton-associated protein   1 . . . 114   114/114 (100%)   2e−60           (CYSKP) #18 -  Homo sapiens , 247 aa.   1 . . . 114   114/114 (100%)           [WO200185942-A2, 15-NOV-2001]       AAM39103   Human polypeptide SEQ ID NO 2248 -   1 . . . 114   114/114 (100%)   2e−60             Homo sapiens , 269 aa. [WO200153312-   47 . . . 160   114/114 (100%)           A1, 26-JUL-2001]       AAG04044   Human secreted protein, SEQ ID NO:   1 . . . 100   93/100 (93%)   2e−49           8125 -  Homo sapiens , 102 aa.   1 . . . 100   97/100 (97%)           [EP1033401-A2, 06-SEP-2000]       AAU33045   Novel human secreted protein #3536 -   1 . . . 83   83/83 (100%)   2e−43             Homo sapiens , 85 aa. [WO200179449-   1 . . . 83   83/83 (100%)           A2, 25-OCT-2001]       AAM40889   Human polypeptide SEQ ID NO 5820 -   1 . . . 114   91/114 (79%)   8e−43             Homo sapiens , 319 aa. [WO200153312-   21 . . . 234   96/114 (83%)           A1, 26-JUL-2001]                  
 
     [0332] 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                                 Protein                       Accession       NOV14a Residues/   Identities/Similarities       Number   Protein/Organism/Length   Match Residues   for the Matched Portion   Expect Value               Q9CV12   5830415L20RIK PROTEIN -  Mus     1 . . . 114   111/114 (97%)   3e−59             musculus  (Mouse), 127 aa (fragment).   1 . . . 114   114/114 (99%)       Q9D292   5830415L20RIK PROTEIN -  Mus     1 . . . 107   103/107 (96%)   2e−54             musculus  (Mouse), 115 aa.   1 . . . 107   105/107 (97%)       Q19670   F21C3.6 PROTEIN -  Caenorhabditis     16 . . . 101   26/96 (27%)   0.025             elegans , 186 aa.   17 . . . 112   44/96 (45%)       CAD25369   HYPOTHETICAL 71.2 KDA   32 . . . 110   25/81 (30%)   0.032           PROTEIN -  Encephalitozoon     298 . . . 375   41/81 (49%)             cuniculi , 606 aa.       O67287   MutS2 protein -  Aquifex aeolicus ,   42 . . . 99   22/62 (35%)   0.032           762 aa.   535 . . . 596   38/62 (60%)                  
 
     [0333] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14E.  
               TABLE 14E                       Domain Analysis of NOV14a                                                Pfam   NOV14a   Identities/Similarities           Domain   Match Region   for the Matched Region   Expect Value                  
 
     Example 15  
     [0334] The NOV15 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15A.  
               TABLE 15A                       NOV15 Sequence Analysis                                                SEQ ID NO:33   483 bp                     NOV15a,     AGCGAAACTCCGCGGAGCGCGCGCGGCACG   ATG GACGGTCGGGTGCAGCTGATGAAGG               CG95452-01 DNA   CCCTCCTGGCCGGGCCCCTCCGGCCCGCGGCGCGTCGCTGGAGGAACCCGATTCCCTT               Sequence   TCCCGAGACGTTTGACGGAGATACCGACCGACTCCCGGAGTTCATCGTGCAGACGAGC                   TCCTACATGTTCGTGGACGAGAACACGTTCTCCAACGACGCCCTGAAGGTGACGTTCC                   TCATCACCCGCCTCACGGGGCCAGCCCTGCAGTGGGTGATCCCCTACATCAGGAAGGA                   GAGCCCCCTGCTCAATGATTACCGGGGCTTCCTGGCCGAGATGAAGCGGGTCTTTGGA                   TGGGAGGAGGACGAGGACTTC TAG   GCCGGGAGACCCTTGGGCCTGGGGGCGGGTGCTC                       TGGGAAGAGTTCGCTGTGCCAGTGGCCACCGCTAGGGTCTCCACAGGCGCCCTCCCTC                       CGCGCCTCCCTCCCCCTCN                                       ORF Start: ATG at 31   ORF Stop: TAG at 370           SEQ ID NO:34   113 aa MW at 13187.9 kD                     NOV15a,   MDGRVQLMKALLAGPLRPAARRWRNPIPFPETFDGDTDRLPEFIVQTSSYMFVDENTF               CG95452-01 Protein   SNDALKVTFLITRLTGPALQWVIPYIRKESPLLNDYRGFLAEMKRVFGWEEDEDF       Sequence                  
 
     [0335] Further analysis of the NOV15a protein yielded the following properties shown in Table 15B.  
               TABLE 15B                       Protein Sequence Properties NOV15a                                        PSort   0.6400 probability located in microbody (peroxisome);       analysis:   0.4500 probability located in cytoplasm;           0.2620 probability located in lysosome (lumen);           0.1000 probability located in mitochondrial matrix space       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0336] 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 for           Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               AAY59927   Human myometrium tumor EST encoded    1 . . . 113   112/113 (99%)   4e−62           protein 7 -  Homo sapiens , 144 aa.    32 . . . 144   112/113 (99%)           [DE19817947-A1, 28-0CT-1999]       AAB60475   Human cell cycle and proliferation protein    1 . . . 113   106/113 (93%)   5e−59           CCYPR-23, SEQ ID NO: 23 -  Homo      1 . . . 113   110/113 (96%)             sapiens , 113 aa. [WO200107471-A2, 01-FEB-2001]       ABG12205   Novel human diagnostic protein #12196 -     6 . . . 113    98/108 (90%)   3e−54             Homo sapiens , 142 aa. [WO200175067-    35 . . . 142   104/108 (95%)           A2, 11-OCT-2001]       ABG12205   Novel human diagnostic protein #12196 -     6 . . . 113    98/108 (90%)   3e−54             Homo sapiens , 142 aa. [WO200175067-    35 . . . 142   104/108 (95%)           A2, 11-OCT-2001]       AAG04029   Human secreted protein, SEQ ID NO:    1 . . . 75    67/75 (89%)   1e−33           8110 -  Homo sapiens , 106 aa.    1 . . . 75    70/75 (93%)           [EP1033401-A2, 06-SEP-2000]                  
 
     [0337] 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               AAH19300   HYPOTHETICAL 13.2 KDA    1 . . . 113   112/113 (99%)   9e−62           PROTEIN -  Homo sapiens  (Human),    1 . . . 113   112/113 (99%)           113 aa.       Q9D1F0   1110012O05RIK PROTEIN (RIKEN    3 . . . 113    79/111 (71%)   1e−38           CDNA 1110012O05 GENE) -  Mus      5 . . . 113    87/111 (78%)             musculus  (Mouse), 113 aa.       Q9DCZ3   1110012O05RIK PROTEIN -  Mus      21 . . . 113    73/93 (78%)   2e−37             musculus  (Mouse), 100 aa.    8 . . . 100    78/93 (83%)       Q9D6I0   2900027G03RIK PROTEIN -  Mus      1 . . . 113    73/114 (64%)   9e−36             musculus  (Mouse), 112 aa.    1 . . . 112    87/114 (76%)       O95751   LDOC1 protein (Leucine zipper protein    26 . . . 112    58/87 (66%)   5e−31           down-regulated in cancer cells) -  Homo      50 . . . 136    73/87 (83%)             sapiens  (Human), 146 aa.                  
 
     [0338] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15E.  
               TABLE 15E                       Domain Analysis of NOV15a                                                Pfam Domain   NOV15a Match   Identities/   Expect Value           Region   Similarities for the               Matched Region                  
 
     Example 16  
     [0339] The NOV16 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16A.  
               TABLE 16A                       NOV16 Sequence Analysis                                                SEQ ID NO:35   1691 bp                     NOV16a,     GTGCGGCGGGCGCGGGCGCCGGAGCGAGGGGCCCGCGGGCCCGGCTATTAATAACGCG                 CG95504-01 DNA     GCCGCCAGCCCGGGGTCGCGCAGCC   ATG GCCAGCCCGGAGCCCCGGCGCGGCGGGGAC               Sequence   GCGCCGCCCAGGCCGCGAGGAAAACAAGAGTAGAGGCCAATTCTCCTCTTCCAAAGA                   ACTCTGGATCCCTAAATGAGGCAGAAGCCTTGAACCCAGAAGTTACTCTATCTTCAGA                   GGGGTCCTTAAACCTCGAAGACATTCTCTACCTGGAGGACACAGGTGACCTTOATGAC                   ACACTCTATGTGCAAGAGACTGAGAAGGCAGAGGAGGCCCTGTATATTGAGGAGGCCA                   TGCAGCCAGATGAGGCTCTGCATGTGGAGGAGCCTGCGAATCCAGAGGAGACAGTGTG                   TGTGGAGGAAACCACGGAGCCAGATCGGATACAGTTTGTGGAGGGGCCCGTGGAGCCA                   GGAAAGCCCACAAGCCCAGAGCACGTTGTTTATGAGGGAGAGACAGTCACAAGGGCGG                   AGAAATCTAACCCTGAGGAGAGCCTCAGAGCCGAGCAGAGCCCCACCGTGGAGGAGAA                   CCTGAGCATAGAGGACCTGGAATTGCTAGAGGGGCGTTTCCAGCAGTGTGTCCAAGCT                   GTGGCCCAGCTGGAAGACCAGACGGATCAGCTCATCCATGAGCTTGTATTGCTCCGGG                   AACCAGCCCTCCAGGACCTACAGCAAGTCCATCAAGACATCCTGGCTGCCTACAAGCT                   CCATGCCCAAGCAGAGCTGGAGAGAGATGGCCTAAGGGAGGAGATCCGGCTGGTCAAG                   CAGAAGCTTTTCAAAGTGACAAAGGAATGTGTGGCCTACCAATACCAGCTGGAGTGCC                   GCCAGCAGGACGTGGCTCAGTTTGCCGATTTCCAGGAAGTGCTGACTACAAGCGCAAC                   CCAGCTCTCAGAGGAACTGGCCCAGCTCCGGGATGCCTATCAGAAGCACAAGGACCAG                   CTGCGGCAACAACTAGAAGCCCCTCCAAGCCAGAGGGATGGGCACTTTCTCCAGGAAA                   GCCGGCGACTCTCTGCCCAGTTTGAAAATCTCATGGCAGACAGCCGCCAGGACCTGGA                   GGAGGAGTATAAGCCTCAGTTCCTGCGGCTCCTAGAGAGGAAAGAAGCTGGGACCAAA                   GCTCTGCAGAGAACCCAGGCTGAGATCCAGGAAATGAAGGAGGCTCTGAGACCCCTGC                   AAGCAGAGGCCCGGCAGCTCCGCCTGCAAAACAGGAACCTGGAGGACCAGATCGCACT                   TGTCAGGCAAAAACGAGATGAAGAGGTGCAGCAGTACAGGGAACAGCTGGAGGAAATG                   GAAGAACGCCAGAGGCAGTTAAGAAATGGGGTGCAACTCCAGCAACAGAAGAACAAAG                   AGATGGAACAGCTAAGGCTCAGTCTTGCTGAAGAGCTCTCTACTTATAAGCCTATGCT                   ACTACCCAAGAGCCTGGAACAGGCTGATGCTCCCACTTCTCAGCCAGGTGGAATGGAG                   ACACAGTCTCAAGCCGCTGTT TAG   AAATATATGGCCAAATCTGTAACCCGGAAACAGC                       AAAAAACTTCTTAGCAAAGGATCACTAAGTACCCTTTGGATGTACTCTTCCAACCAGA                       CAAGAGTGCCAGAAACTTGGCAAGCAATTCATCCTGTGGAAGTTGCAATACTGGCTGC                       CTGCTTAAA                                       ORF Start: ATG at 84   ORF Stop: TAG at 1530           SEQ ID NO:36   482 aa MW at 55237.8 kD                     NOV16a,   MASPEPRRGGDGAAQAARKTRVEANSPLPKNSGSLNEAEALNPEVTLSSEGSLNLEDI               CG95504-01 Protein   LYLEDTGDLDETLYVQETEKAEEALYIEEAMQPDEALHVEEPGNPEETVCVEETTEPD               Sequence   RIQFVEGPVEPGKPTSPEHVVYEGETVTRAEKSNPEESLRAEQSPSVEENLSIEDLEL                   LEGRFQQCVQAVAQLEEERDQLIHELVLLREPALQEVQQVHQDILAAYKLHAQAELER                   DGLREEIRLVKQKLFKVTKECVAYQYQLECRQQDVAQFADFQEVLTTRATQLSEELAQ                   LRDAYQKQKEQLRQQLEAPPSQRDGHFLQESRRLSAQFENLMAESRQDLEEEYKPQFL                   RLLERKEAGTKALQRTQAEIQEMKEALRPLQAEARQLRLQNRNLEDQIALVRQKRDEE                   VQQYREQLEEMEERQRQLRNGVQLQQQKNKEMEQLRLSLAEELSTYKAMLLPKSLEQA                   DAPTSQAGGMETQSQGAV                                     SEQ ID NO:37   1611 bp                     NOV16b,     GTGCGGCGGGCGCGGGCGCCGGAGCGAGGGGCCCGCGGGCCCGGCTATTAATAACGCG                 CG95504-02 DNA     GCCGCCAGCCCGGGGTCGCGCAGCC   ATG GCCAGCCCGGAGCCCCGGCGCGGCGGGGAC               Sequence   GGCGCCGCCCAGGCCGCGAGCAAAACAACAGTAGAGGCCAATTCTCCTCTTCCAAAGA                   ACTCTGGATCCCTAAATGAGGCAGAAGCCTTGAACCCACAAGTTACTCTATCTTCAGA                   GGGGTCCTTAAACCTCGAAGACATTCTCTACCTGGAGGACACAGGTGACCTTGATGAG                   ACACTCTATGTGCAAGAGACTGAGAAGGCAGAGGAGGCCCTGTATATTGACGAGGCCA                   TCCAGCCACATGAGGCTCTGCATGTGGAGGAGCCTGGGAATCCAGACGAGACAGTGTG                   TGTGGAGGAAACCACGGAGCCAGATCGGATACAGTTTGTGGAGGCGCCCGTGGAGCCA                   GGAAAGCCCACAAGCCCAGAGCACGTTGTTTATGAGGGACAGACAGTCACAAGGGCGG                   AGAAATCTAACCCTGAGGAGAGCCTCAGAGCCGAGCAGAGCCCCAGCGTGGAGGAGAA                   CCTGAGCATAGAGGACCTGGAATTGCTAGACGGGCGTTTCCAGCAGTGTGTCCAAGCT                   GTGGCCCAGCTGGAAGAGGAGAGGGATCAGCTCATCCATGAGCTTGTATTGCTCCGGG                   AACCAGCCCTGCAGGAGGTACAGCAAGTCCATCAAGACATCCTGGCTGCCTACAAGCT                   CCATGCCCAAGCAGAGCTGGAGAGAGATGGCCTAAGOGAGGAGATCCGGCTGGTCAAG                   CAGAAGCTTTTCAAAGTGACAAAGGAATGTGTGCCCTACCAATACCAGCTGGAGTGCC                   GCCAGCAGGACGTGGCTCAGTTTGCCGATTTCCAGGAAGTGCTGACTACAAGGGCAAC                   CCAGCTCTCAGAGGAACTGGCCCAGCTCCCGGATGCCTATCAGAAGCAGAAGGAGCAG                   CTGCGGCAACAACTAGAAGCCCCTCCAAGCCAGAGGGATGGGCACTTTCTCCAGGAAA                   GCCGGCGACTCTCTGCCCAGTTTGAAAATCTCATGGCAGAGAGCCGCCAGGACCTGGA                   GGAGGAGTATGAGCCTCAGTTCCTGCGGCTCCTAGAGAGGAAAGAAGCTGGGACCAAA                   GCTCTGCACAGAACCCAGGCTGAGATCCAGGAAATGAAGGAGGCTCTGAGACCCCTGC                   AAGCAGAGGCCCGGCAGCTCCGCCTGCAAAACAGGAACCTGCAGGACCAGATCGCACT                   TGTGAGGCAAAAACGAGATGAAGAGGTGCAGCAGTACAGGGAACAGCTGGAGGAAATG                   GAAGAACGCCAGAGGCAGTTAAGAAATGGGGTGCAACTCCAGCAACAGAAGAACAAAG                   AGATGGAACAGCTAAGGCTCAGTCTTGCTGAAGAGCTCTCTACTTATAAGGGCTGTTT                   AGAAATATATGGCCAAATCTGTAACCCGGAAACAGCAAAAAACTTCTTAGCAAAGGAT                   CAC TAA   GTACCCTTTGGATGTACTCTTCCAACCAGACAAGAGTGCCAGAAACTTGGCA                       AGCAATTCATCCTGTGGAAGTTGCAATACTGGCTGCCTGCTTAAA                                       ORF Start: ATG at 84   ORF Stop: TAA at 1512           SEQ ID NO:38   476 aa MW at 54886.4 kD                     NOV16b,   MASPEPRRGGDGAAQAARKTRVEANSPLPKNSGSLNEAEALNPEVTLSSEGSLNLEDI               CG95504-02 Protein   LYLEDTGDLDETLYVQETEKAEEALYIEEAMQPDEALHVEEPGNPEETVCVEETTEPD               Sequence   RIQFVEGPVEPGKPTSPEHVVYECETVTRAEKSNPEESLRAEQSPSVEENLSIEDLEL                   LEGRFQQCVQAVAQLEEERDQLIHELVLLREPALQEVQQVHQDILAAYKLHAQAELER                   DGLREEIRLVKQKLFKVTKECVAYQYQLECRQQDVAQFADFQEVLTTRATQLSEELAQ                   LRDAYQKQKEQLRQQLEAPPSQRDGHFLQESRRLSAQFENLMAESRQDLEEEYEPQFL                   RLLERKEAGTKALQRTQAEIQEMKEALRPLQAEARQLRLQNRNLEDQIALVRQKRDEE                   VQQYREQLEEMEERQRQLRNGVQLQQQKNKEMEQLRLSLAEELSTYKGCLEIYGQICN                   PETAKNFLAKDH                  
 
     [0340] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 16B.  
               TABLE 16B                          Comparison of NOV16a against NOV16b.                             NOV16a Residues/   Identities/Similarities       Protein Sequence   Match Residues   for the Matched Region               NOV16b   1 . . . 456   400/456 (87%)           1 . . . 456   401/456 (87%)                  
 
     [0341] Further analysis of the NOV16a protein yielded the following properties shown in Table 16C.  
               TABLE 16C                       Protein Sequence Properties NOV16a                                        PSort   0.6500 probability located in cytoplasm;       analysis:   0.1000 probability located in mitochondrial matrix space;           0.1000 probability located in lysosome (lumen);           0.0000 probability located in endoplasmic           reticulum (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0342] A search of the NOV16a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16D.  
               TABLE 16D                          Geneseq Results for NOV16a                                         NOV16a   Identities/                   Residues/   Similarities for           Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               ABB57243   Mouse ischaemic condition related protein   154 . . . 456    77/322 (23%)   6e−20           sequence SEQ ID NO: 650 -  Mus      23 . . . 340   148/322 (45%)             musculus , 403 aa. [WO200188188-A2,           22-NOV-2001]       AAY20975   Human glial fibrillary acidic protein   119 . . . 456    81/358 (22%)   3e−19           GFAP wild type fragment 1 -  Homo      20 . . . 371   160/358 (44%)             sapiens , 433 aa. [WO9845322-A2, 15-OCT-1998]       AAB66348   Human vimentin -  Homo sapiens , 466 aa.   171 . . . 456    66/299 (22%)   1e−17           [EP1067142-A1, 10-JAN-2001]   106 . . . 404   148/299 (49%)       AAY92335   Human vimentin -  Homo sapiens , 466 aa.   171 . . . 456    66/299 (22%)   1e−17           [WO200020448-A2, 13-APR-2000]   106 . . . 404   148/299 (49%)       AAB29635   Human pollinosis-associated gene 795-   171 . . . 456    66/299 (22%)   1e−17           encoded protein, SEQ ID NO: 26 -  Homo     106 . . . 404   148/299 (49%)             sapiens , 466 aa. [WO200065050-A1, 02-NOV-2000]                  
 
     [0343] In a BLAST search of public sequence datbases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16E.  
               TABLE 16E                          Public BLASTP Results for NOV16a                                         NOV16a   Identities/           Protein       Residues/   Similarities for           Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9EPM5   SYNCOILIN -  Mus musculus  (Mouse),    1 . . . 482   369/483 (76%)   0.0           470 aa.    1 . . . 470   405/483 (83%)       Q9CT88   1110057H03RIK PROTEIN -  Mus     242 . . . 463   191/222 (86%)    e−102             musculus  (Mouse), 223 aa (fragment).    1 . . . 222   205/222 (92%)       Q9H7C4   CDNA: FLJ21054 FIS, CLONE   332 . . . 482   150/151 (99%)   6e−77            CAS00538 -  Homo sapiens  (Human), 151    1 . . . 151   151/151 (99%)           aa.       Q8VCW5   SIMILAR TO ALPHA INTERNEXIN   170 . . . 456    79/305 (25%)   8e−22            NEURONAL INTERMEDIATE    96 . . . 400   150/305 (48%)           FILAMENT PROTEIN -  Mus musculus             (Mouse), 501 aa.       P23565   Alpha-internexin (Alpha-Inx) -  Rattus     170 . . . 456    79/305 (25%)   8e−22              norvegicus  (Rat), 505 aa.    96 . . . 400   150/305 (48%)                  
 
     [0344] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16F.  
               TABLE 16F                       Domain Analysis of NOV16a                                                Pfam Domain   NOV16a Match   Identities/   Expect Value           Region   Similarities for the               Matched Region                  
 
     Example 17  
     [0345] The NOV17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A.  
               TABLE 17A                       NOV17 Sequence Analysis                                                SEQ ID NO:39   897 bp                     NOV17a,     GCAGGACGGAACCCGCCCTGCGCTCCACACCTGAGGCCGCTCCCTTCGCCTCTTCTCC                 CG95589-01 DNA     TCAGGTGCTGTCCTTATTCCCAGCCCAGTCAAGAGCTACCGGGGCTGGCTAGTC   ATG G               Sequence   GGGAGCCCAGTAGAGAGGAGTATAAAATCCAGTCCTTTGATGCAGAGACCCAGCAGCT                   GCTGAAGACAGCACTCAAAGATCCGGGTGCTGTGGACTTCGAGAAAGTGGCCAATGTG                   ATTGTGGACCATTCTCTGCAGGACTGTGTGTTCAGCAAGGAAGCAGGACGCATGTGCT                   ACGCCATCATTCAGGCAGAGAGTAAACAAGCAGGCCAGAGTGTCTTCCGACGTGGACT                   CCTCAACCGGCTGCAGCAGGAGTACCAGGCTCGGGAGCAGCTGCGAGCACGCTCCCTG                   CAGGGCTGGGTCTGCTATGTCACCTTTATCTGCAACATCTTTGACTACCTGAGGGTGA                   ACAACATGCCCATGATGGCCCTGGTGAACCCTGTCTATGACTGCCTCTTCCGGCTGGC                   CCAGCCAGACAGTTTGAGCAAGGAGGAGGAGGTGGACTGTTTGGTGCTGCAGCTGCAC                   CGGGTTGGGGAGCAGCTGGAGAAAATGAATGGGCAGCGCATGGATGAGCTCTTTGTGC                   TGATCCGGGATGGCTTCCTGCTCCCAACTGGCCTCAGCTCCCTGGCCCAGCTGCTGCT                   GCTGGAGATCATTGAGTTCCGGGCGGCCGGCTGGAAGACAACGCCAGCTCCCCACAAG                   TATTACTACAGCGAAGTCTCCGAC TAG   GCCTCCAGATCAGGGCTTCCTCACCAGCACT                       GGCCTTTCTTCTACCCACCTCTAAAGCTGGCAGTGGAGTCTCTGCCTCACCCAAAGAC                       TTTTCCCTTCCAGACTTTGAGTGTCTT                                       ORF Start: ATG at 113   ORF Stop: TAG at 779           SEQ ID NO:40   222 aa MW at 25422.9 kD                     NOV17a,   MGEPSREEYKIQSFDAETQQLLKTALKDPGAVDLEKVANVIVDHSLQDCVFSKEAGRM               CG95589-01 Protein   CYAIIQAESKQAGQSVFRRGLLNRLQQEYQAREQLRARSLQGWVCYVTFICNIFDYLR               Sequence    VNNMPMMALVNPVYDCLFRLAQPDSLSKEEEVDCLVLQLHRVGEQLEKMNGQRMDELF                   VLIRDGFLLPTGLSSLAQLLLLEIIEFRAAGWKTTPAAHKYYYSEVSD                                     SEQ ID NO:41   826 bp                     NOV17b,     CTCTTCTCCTCAGGTGCTGTCCTTATTCCCAGCCCATACAAGAGCTACCGGGGCTGGC                 CG95589-02 DNA     TAGTC   ATG GGGGAGCCCAGTACAGAGGAGTATAAAATCCAGTCCTTTGATGCAGAGAC               Sequence   CCAGCAGCTGCTGAAGACAGCACTCAAAGATCCGGGTCCTCTGGACTTGGAGAAACTG                   GCCAATGTGATTGTGGACCATTCTCTGCAGGACTGTGTGTTCAGCAAGGAAGCAGGAC                   GCATGTCCTACGCCATCATTCAGGCAGAGAGTAAACAAGCAGGCCAGAGTGTCTTCCG                   ACGTGGACTCCTCAACCGGCTGCAGCAGGAGTACCAGGCTCGGGAGCAGCTGCGAGCA                   CGCTCCCTGCAGGGCTGGGTCTGCTATGTCACCTTTATCTGCAACATCTTTGACTACC                   TGAGGGTGAACAACATGCCCATGATGGCCCTGGTCAACCCTGTCTATGACTCCCTCTT                   CCGGCTGGCCCAGCCAGACAGTTTGAGCAAGGAGGAGGAGGTGGACTGTTTGGTGCTG                   CAGCTGCACCGGGTTCGGGAGCAGCTGGAGAAAATGAATGGGCAGCGCATGGATGAGC                   TCTTTGTGCTGATCCGGGATGGCTTCCTGCTCCCAACTGGCCTCAGCTCCCTGGCCCA                   GCTGCTGCTGCTGGAGATCATTGAGTTCCGGGCGGCCGGCTCGAAGACAACCCCAGCT                   GCCCACAAGTATTACTACAGCGAAGTCTCCGAC TAG   GCCTCCAGATCAGGGCTTCCTC                       ACCAGCACTCGCCTTTCTTCTACCCACCTCTAAAGCTGGCAGTGGAGTCTCTGCCTCA                       CCCAAAGACTTTTC                                       ORF Start: ATG at 64   ORF Stop: TAG at 730           SEQ ID NO:42   222 aa MW at 25367.9 kD                     NOV17b,   MGEPSTEEYKIQSFDAETQQLLKTALKDPGAVDLEKVANVIVDHISLQDCVFSKEAGRM               CG95589-02 Protein   CYAIIQAESKQAGQSVFRRGLLNRLQQEYQAREQLRARSLQGWVCYVTFICNIFDYLR               Sequence    VNNMPMMALVNPVYDCLFRLAQPDSLKEEEVDCLVLQLHRVGEQLEKMNGQRMDELF                   VLTRDGFLLPTGLSSLAQLLLLEIIEFRAAGWKTTPAAHKYYYSEVSD                  
 
     [0346] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 17B.  
               TABLE 17B                          Comparison of NOV17a against NOV17b.                             NOV17a Residues/   Identities/Similarities       Protein Sequence   Match Residues   for the Matched Region               NOV17b   1 . . . 222   206/222 (92%)           1 . . . 222   206/222 (92%)                  
 
     [0347] Further analysis of the NOV17a protein yielded the following properties shown in Table 17C.  
               TABLE 17C                       Protein Sequence Properties NOV17a                                        PSort   0.6500 probability located in cytoplasm;       analysis:   0.1000 probability located in mitochondrial matrix space;           0.1000 probability located in lysosome (lumen);           0.0000 probability located in endoplasmic           reticulum (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0348] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17D.  
               TABLE 17D                          Geneseq Results for NOV17a                                         NOV17a   Identities/                   Residues/   Similarities for           Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value                                             AAB42861   Human ORFX ORF2625 polypeptide    1 . . . 191   191/191   (100%)    e−107           sequence SEQ ID NO: 5250 -  Homo     27 . . . 217   191/191   (100%)             sapiens , 217 aa. [WO200058473-A2, 05           Oct. 2000]       AAY00354   Fragment of human secreted protein    1 . . . 164   162/164   (98%)   4e−89           encoded by gene 26 -  Homo sapiens , 196   33 . . . 196   162/164   (98%)           aa. [WO9906423-A1, 11 Feb. 1999]       AAM38210   Peptide #12247 encoded by probe for   148 . . . 222    75/75   (100%)   8e−37           measuring placental gene expression -   1 . . . 75   75/75   (100%)             Homo sapiens , 75 aa. [WO200157272-           A2, 09 Aug. 2001]       AAM21883   Peptide #8317 encoded by probe for   148 . . . 222    75/75   (100%)   8e−37           measuring cervical gene expression -   1 . . . 75   75/75   (100%)             Homo sapiens , 75 aa. [WO200157278-           A2, 09 Aug. 2001]       AAM77990   Human bone marrow expressed probe   148 . . . 222    75/75   (100%)   8e−37           encoded protein SEQ ID NO: 38296 -   1 . . . 75   75/75   (100%)             Homo sapiens , 75 aa. [WO200157276-           A2, 09 Aug. 2001]                  
 
     [0349] In a BLAST search of public sequence datbases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17E.  
               TABLE 17E                          Public BLASTP Results for NOV17a                                         NOV17a   Identities/           Protein       Residues/   Similarities for           Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                             Q9D6M8   2310075G12RIK PROTEIN -  Mus     1 . . . 222   207/222   (93%)    e−117             musculus  (Mouse), 222 aa.   1 . . . 222   217/222   (97%)       Q9HBL5   AD023 -  Homo sapiens  (Human),   1 . . . 191   162/191   (84%)   1e−84           305 aa.   1 . . . 191   165/191   (85%)       O43310   Hypothetical protein KIAA0427 -   34 . . . 216    62/187   (33%)   2e−19             Homo sapiens  (Human), 598 aa.   410 . . . 589    97/187   (51%)       Q9VL73   CG13124 PROTEIN -  Drosophila     11 . . . 222    59/232   (25%)   1e−12             melanogaster  (Fruit fly), 510 aa.   285 . . . 510    110/232   (46%)       T29786   hypothetical protein F44A2.5 -   75 . . . 222    43/150   (28%)   2e−10             Caenorhabditis elegans , 345 aa.   200 . . . 345    81/150   (53%)                  
 
     [0350] PFam analysis predicts that the NOV17a protein contains the domains shown in the Table 17F.  
               TABLE 17F                          Domain Analysis of NOV17a                                     Identities/               NOV17a Match   Similarities   Expect       Pfam Domain   Region   for the Matched Region   Value               MIF4G   3 . . . 205    45/233 (19%)   0.0041               127/233 (55%)                  
 
     Example 18  
     [0351] 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:43   541 bp                     NOV18a,     GAGGACAGACTGCCGTGTTGCCACCACAGGCTGGACC   ATG GACCCCCAAGGAATGGTC               CG95598-01 DNA   GTCAAGAACCCATATGCCCACATCAGCATCCCCCGGGCTCACCTGCGGCCTGACCTGG               Sequence   GGCAGCAGTTAGAGGTGGCTTCCACCTGTTCCTCATCCTCGGAGATGCAGCCCCTGCC                   AGTGGGGCCCTGTGCCCCAGAGCCAACCCACCTCTTGCAGCCGACCGAGGTCCCAGGG                   CCCAAGGGCGCCAAGGGTAACCAGGGGGCTGCCCCCATCCAGAACCACCAGGCCTGGC                   AGCAGCCTGGCAACCCCTACAGCAGCAGTCAGCGCCAGGCCGGACTGACCTACGCTGG                   CCCTCCGCCCGTGGGGCGCGGGGATGACATCGCCCACCACTGCTGCTGCTGCCCCTGC                   TGCCACTGCTGCCACTGCCCCCCCTTCTGCCGCTGCCACAGCTGCTGCTGCTGTGTCA                   TCTCC TAG   CCCAGCCCACCCTGCCAGGACCAGGACCCAGACTTCAACAAATGTGGCTC                       ACACAGTGCCGGGACATGC                                       ORF Start: ATG at 38   ORF Stop: TAG at 470           SEQ ID NO:44   144 aa MW at 15269.3 kD                     NOV18a,   MDPQGMVVKNPYAHISIPRAHLRPDLGQQLEVASTCSSSSEMQPLPVGPCAPEPTHLL               CG95598-01 Protein   QPTEVPGPKGAKGNQGAAPIQNQQAWQQPGNPYSSSQRQAGLTYAGPPPVGRGDDIAH               Sequence   HCCCCPCCHCCHCPPFCRCHSCCCCVIS                  
 
     [0352] Further analysis of the NOV18a protein yielded the following properties shown in Table 18B.  
               TABLE 18B                       Protein Sequence Properties NOV18a                                        PSort   0.6500 probability located in plasma membrane; 0.4500       analysis:   probability located in cytoplasm; 0.3000 probability located           in microbody (peroxisome); 0.1000 probability located in           mitochondrial matrix space       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0353] A search of the NOV18a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 18C.  
               TABLE 18C                          Geneseq Results for NOV18a                                             Identities/                   NOV18a   Similarities                   Residues/   for the           Geneseq   Protein/Organism/Length [Patent #,   Match   Matched   Expect       Identifier   Date]   Residues   Region   Value                                         ABG08718   Novel human diagnostic protein #8709 -   46 . . . 122   31/83 (37%)   0.004             Homo sapiens , 375 aa. [WO200175067-   92 . . . 167   37/83 (44%)           A2, 11 Oct. 2001]       ABG08718   Novel human diagnostic protein #8709 -   46 . . . 122   31/83 (37%)   0.004             Homo sapiens , 375 aa. [WO200175067-   92 . . . 167   37/83 (44%)           A2, 11 Oct. 2001]       AAB51183   Human sulfatase protein A SEQ ID NO: 12   94 . . . 130   19/41 (46%)   0.017           -  Homo sapiens , 507 aa. [US6153188-A,   464 . . . 503    23/41 (55%)           28 Nov. 2000]       AAE09804   Consensus human phorbol activated   37 . . . 113   24/79 (30%)   0.049           nuclear factor-like protein (PNF1) -  Homo     445 . . . 519    32/79 (40%)             sapiens , 584 aa. [WO200162790-A2, 30           Aug. 2001]       AAM50386   Wheat glutenin variant 1A × 2asteriskB -   23 . . . 111   29/95 (30%)   0.084             Triticum aestivum , 434 aa.   196 . . . 290    38/95 (39%)           [WO200179477-A2, 25 Oct. 2001]                  
 
     [0354] 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 18D.  
               TABLE 18D                          Public BLASTP Results for NOV18a                                         NOV18a   Identities/           Protein       Residues/   Similarities for           Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                             Q9D1E4   2310002J15RIK PROTEIN -  Mus     1 . . . 139   107/139   (76%)   5e−64             musculus  (Mouse), 142 aa.   1 . . . 139   110/139   (78%)       Q9D7M7   2310002J15RIK PROTEIN -  Mus     1 . . . 139   106/139   (76%)   1e−63             musculus  (Mouse), 142 aa.   1 . . . 139   110/139   (78%)       Q8WZL5   SIN3 PROTEIN -  Yarrowia lipolytica     16 . . . 137    41/130   (31%)   0.023           ( Candida lipolytica ), 1527 aa.   149 . . . 248    49/130   (37%)       Q96CJ0   SIMILAR TO ARYLSULFATASE A -   94 . . . 130    19/41   (46%)   0.039             Homo sapiens  (Human), 509 aa.   466 . . . 505    23/41   (55%)       P15289   Arylsulfatase A precursor (EC 3.1.6.8)   94 . . . 130    19/41   (46%)   0.039           (ASA) (Cerebroside-sulfatase) -  Homo     464 . . . 503    23/41   (55%)             sapiens  (Human), 507 aa.                  
 
     [0355] PFam analysis predicts that the NOV18a protein contains the domains shown in the Table 18E.  
               TABLE 18E                          Domain Analysis of NOV18a                                     Identities/                   Similarities for   Expect       Pfam Domain   NOV18a Match Region   the Matched Region   Value                  
 
     Example 19  
     [0356] 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:45   531 bp                     NOV19a,   ATGAAGCCCCTGCTCCTGGCCATCAGCCTCAGCCTCATTGCTGCCCTGCAGGCCCACC               CG95639-01 DNA   ACCTCCTGGCCTCAGACGAGGAGATTCAGGATGTGTCAGGGACGTGGTATCTGAAGGC               Sequence   CATCACGGTGGACAGGGAGCTCCCTGAGATGAATCTGGAATCGGTGACACCCATGACC                   CTCACAATCCTGGAAGGGGGCAACCTGGAAGCTAAGGCCACCATGCTGATAAGTGGCC                   AGTGCCAGGAGGTGAAGGTCGTCCTGGAGAAAACTGACGAGCCGGGAAAATACACGGC                   CGACAGGGGCAAGCACGTGGCATACATCATCAGGTCGCACGTGAAGGACCACTACATC                   TTTTACTGTGAGGGTGAGCTGCACGGGAAGCCGATCCGAGGGGCGAAGCTCGTGGGTA                   GAGACCCCGAGAACAACCTGGAAGCCTTGGAGGACTTTGAGAAAGCTGCAGGAGCCCG                   TGGACTCAGCACGGAGAGCATCCTCATCCCCAGGCAGAGCGAAACCTGCTCTCCAGGG                   AGCGAT TAG                                       ORF Start: ATG at 1   ORF Stop: TAG at 529           SEQ ID NO:46   176 aa MW at 19329.8 kD                     NOV19a,   MKPLLLAISLSLIAALQAHHLLASDEEIQDVSGTWYLKAMTVDRELPEMNLESVTPMT               CG95639-01 Protein   LTILEGGNLEAKATMLISGQCQEVKVVLEKTDEPGKYTADRGKHVAYIIRSHVKDHYI               Sequence   FYCEGELHGKPIRGAKLVGRDPENNLEALEDFEKAAGARGLSTESILIPRQSETCSPG                   SD                  
 
     [0357] Further analysis of the NOV19a protein yielded the following properties shown in Table 19B.  
               TABLE 19B                       Protein Sequence Properties NOV19a                                        PSort   0.4753 probability located in outside; 0.1000 probability       analysis:   located in endoplasmic reticulum (membrane); 0.1000 prob-           ability located in endoplasmic reticulum (lumen); 0.1000           probability located in microbody (peroxisome)       SignalP   Cleavage site between residues 19 and 20       analysis:                  
 
     [0358] 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 [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               AAG66536   Human interferon-alpha induced   1 . . . 176   165/176 (93%)   9e−93           polypeptide, Lipocalin 1 -  Homo sapiens ,   1 . . . 176   169/176 (95%)           176 aa. [WO200159155-A2, 16 Aug.           2001]       ABG29411   Novel human diagnostic protein #29402 -   1 . . . 170   168/170 (98%)   5e−92             Homo sapiens , 865 aa. [WO200175067-   1 . . . 170   169/170 (98%)           A2, 11 Oct. 2001]       ABG29411   Novel human diagnostic protein #29402 -   1 . . . 170   168/170 (98%)   5e−92             Homo sapiens , 865 aa. [WO200175067-   1 . . . 170   169/170 (98%)           A2, 11 Oct. 2001]       AAY25670   Dog allergen Can f 1 protein fragment -   1 . . . 174   107/174 (61%)   1e−50             Canis sp , 174 aa. [WO9934826-A1, 15   1 . . . 172   125/174 (71%)           Jul. 1999]       AAR59987   Can fI protein allergen -  Canis familiaris ,   1 . . . 174   107/174 (61%)   1e−50           174 aa. [WO9416068-A, 21 Jul. 1994]   1 . . . 172   125/174 (71%)                  
 
     [0359] 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   Identities/           Protein       Residues/   Similarities for           Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               P31025   Von Ebner&#39;s gland protein precursor   1 . . . 176   165/176 (93%)   2e−92           (VEG protein) ( Tear prealbumin ) (TP)   1 . . . 176   169/176 (95%)           ( Tear lipocalin ) (Lipocalin 1) -  Homo               sapiens  (Human), 176 aa.       P53715   Von Ebner&#39;s gland protein precursor   1 . . . 176   105/176 (59%)   1e−52           (VEG protein) ( Tear prealbumin ) (TP)   2 . . . 176   132/176 (74%)           ( Tear lipocalin ) (Lipocalin-1) -  Sus scrofa             (Pig), 176 aa.       P41244   Von Ebner&#39;s gland protein 2 precursor   1 . . . 176   108/178 (60%)   2e−51           (VEG protein 2) -  Rattus norvegicus     1 . . . 177   129/178 (71%)           (Rat), 177 aa.       O18873   Major allergen Can f 1 precursor   1 . . . 174   107/174 (61%)   3e−50           (Allergen Dog 1) -  Canis familiaris  (Dog),   1 . . . 172   125/174 (71%)           174 aa.       P20289   Von Ebner&#39;s gland protein 1 precursor   1 . . . 176   105/178 (58%)   4e−50           (VEG protein 1) -  Rattus norvegicus     1 . . . 177   127/178 (70%)           (Rat), 177 aa.                  
 
     [0360] PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19E.  
               TABLE 19E                          Domain Analysis of NOV19a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV19a Match Region   for the Matched Region   Value                                         lipocalin   30 . . . 171   48/157   (31%)   7.2e−37               116/157   (74%)                  
 
     Example 20  
     [0361] 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:47   1218 bp                     NOV20a,     TCCTCTGTCACGGGCTGCTGAACCCGAGCTGGTGTGAGCTTCTCTTGCCGTAAGTCCA                 CG95649-01 DNA     CGGGTGGCCAGGAGCACGTGTTAGTCTGGTTAAGAGCTCTGCTCAGAAGTAGCCGCTG                 Sequence     CAGCTGAAGGTTTTCAGGCGGGCTGAAGGCTGGGCCGCTTCTTCATTCATTTCAGAAA                       CTTGAACAGTGGGCCTTCTACACACGCTGTCTTTGTCAGCCTCAGGCAGTTCCTCC   AT                       G GATGAGACACAGGGGCCTCTGGCCATGACTGTCCATCTTCTTGCCAACTCTGGGCAC                   GGCTCCCTTCTGCAGAGGACTCTGGACCAGCTCCTGGATTGCATTTGCCCAGAGGTCC                   GGCTCTTTCAGGTGTCTGAACGGGCCAGTCCTGTGAAATACTGTGAAAAGTCCCATTC                   CAAGCGGTCCCGGTTTCCAGGGATGTCCGTGTTGCTCTTCCTGCACGAAAGCCCGGGA                   GAGGATAGGCTATTTCGCGTCCTGGACTCTCTCCAGCATTCGCCATGGCAGTGCTACC                   CCACCCACGACACTCGGGGAAGGCTGTGTCCCTACTTTTTTGCCAATCAGGAGTTCTA                   CAGCCTGGACAGTCACCTGCCCATCTGCGGGGTGAGGCACGTGCACTGTGGCTCCGAG                   ATCCTGAGCGTGACGCTGTACTGCAGTTTTCATAACTATGAAGACGCCATCAGACTCT                   ACGAGATGATCCTGCAGAGAGAAGCGACCTTGCAAAAGAGCAATTTTTGTTTCTTCGT                   GCTCTATGCCTCCAAGAGCTTTGCTCTGCAGCTCTCCCTGAAGCAGCTGCCCCCGGGA                   ATGTCAGTGGACCCCAAAGAGTCTTCGGTGCTGCAGTTTAAGGTTCAAGAGATCCGCC                   AGTTAGTGCCTCTGCTACCCAATCCATGCATGCCTATCAGCAGCACCAGGTGGCAGAC                   TCAGGACTACGATGCCAACAAGATTCTGCTTCAGGTCCAGCTGAATCCAGAACTTCGT                   GTTAAGAATGGCACCTTGGGAGCTGGCATGCTTCCCCTGGGCTCCAGGCTGACTTCTG                   TCTCTGCAAAGAGGACCTCAGAACCCAGGAGCCAGAGGAACCAGGGCAAGAGGTCCCA                   GGGGCATTCTCTGGACCTTCCTGAGCCCAGTGGGAGCCCCACATCAGACACGTGTGCT                   GGCACTTCGTGGAAAAGCCCTGGCCGGTCATTCCAGGTCAGCAGCCCGTGACAGAGGA                                     ORF Start: ATG at 234   ORF Stop: TGA at 1209           SEQ ID NO:48   326 aa MW at 36633.4 kD                     NOV20a,   MDETQGPLAMTVHLLANSGHGSLLQRTLDQLLDCICPEVRLFQVSERASPVKYCEKSH               CG95649-01 Protein   SKRSRFPGMSVLLFLHESPGEDRLFRVLDSLQNSPWQCYPTQDTRCRLCPYFFANQEF               Sequence   YSLDSQLPIWGVRQVHCGSEILRVTLYCSFDNYEDAIRLYEMILQREATLQKSNFCFF                   VLYASKSFALQLSLKQLPPGMSVDPKESSVLQFKVQEIGQLVPLLPNPCMPISSTRWQ                   TQDYDGNKILLQVQLNPELGVKNGTLGAGMLPLGSRLTSVSAKRTSEPRSQRNQGKRS                   QGHSLELPEPSGSPTSDRCAGTSWKSPGRSFQVSSP                  
 
     [0362] 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 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:                  
 
     [0363] 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                                             ABG01087   Novel human diagnostic protein #1078 -   1 . . . 244   227/244   (93%)    e−131             Homo sapiens , 414 aa. [WO200175067-   132 . . . 366   231/244   (94%)           A2, 11 OCT. 2001]       ABG01087   Novel human diagnostic protein #1078 -   1 . . . 244   227/244   (93%)    e−131             Homo sapiens , 414 aa. [WO200175067-   132 . . . 366   231/244   (94%)           A2, 11 OCT. 2001]       AAM93553   Human polypeptide, SEQ ID NO:3317 -   262 . . . 326   65/65   (100%)   3e−31             Homo sapiens , 194 aa. [EP1130094-A2,   1 . . . 65   65/65   (100%)           05 SEP. 2001]       AAM02888   Peptide #1570 encoded by probe for   253 . . . 307   54/55   (98%)   1e−23           measuring breast gene expression -  Homo     1 . . . 55   54/55    (98%)             sapiens , 55 aa. [WO200157270-A2, 09           AUG. 2001]       AAM27604   Peptide #1641 encoded by probe for   253 . . . 307   54/55   (98%)   1e−23           measuring placental gene expression -   1 . . . 55   54/55   (98%)             Homo sapiens , 55 aa. [WO200157272-A2,           09 AUG. 2001]                  
 
     [0364] 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                                             Q9H5Z6   CDNA: FLJ22746 FIS, CLONE   1 . . . 264   261/264   (98%)    e−153           HUV01174 -  Homo sapiens  (Human),   1 . . . 264   261/264   (98%)           268 aa.       AAH25754   SIMILAR TO HYPOTHETICAL   1 . . . 244   244/244   (100%)    e−143           PROTEIN FLJ22746 -  Homo sapiens     1 . . . 244   244/244   (100%)           (Human), 272 aa.       Q96NJ9   CDNA FLJ30707 FIS, CLONE   1 . . . 246   103/246   (41%)   9e−58           FCBBF2001211 -  Homo sapiens     38 . . . 280   164/246   (65%)           (Human), 546 aa.       Q9Z103   ACTIVITY-DEPENDENT   251 . . . 315   20/67   (29%)   7.6           NEUROPROTECTIVE PROTEIN -   100 . . . 166   28/67   (40%)             Mus musculus  (Mouse), 828 aa.       O84671   (FHA DOMAIN, HOMOLOGY TO   226 . . . 306   28/99   (28%)   7.6           ADENYLATE CYCLASE) -   186 . . . 284   37/99   (37%)           Chlamydia trachomatis, 829 aa.                  
 
     [0365] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20E.  
               TABLE 20E                       Domain Analysis of NOV20a                                                        Identities/           Pfam       Similarities   Expect       Domain   NOV20a Match Region   for the Matched Region   Value                  
 
     Example 21  
     [0366] 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:49   2730 bp                     NOV21a,   CGTTTCGTCCGGGGCCGCGGCGGCCATGGGGAATCGGCTGCAGCGAATCGGTGGCGCG               CG95775-01 DNA   CGGGGCCTGAGCGCGCTGCAGTCACCCGGGAGCCGGGTCCAGGTCGTCTTCCCGGGAC               Sequence   GCCCGGATCTGTCCTGCAGGATGGAGCCAGCACCCTCAGAGGTTCGACTCGCCGTCCG                   GGAAGCCATTCATGCCCTCTCGTCTTCGGAGGATGGCGGCCACATCTTCTGCACCCTG                   GACTCCCTGAAGCGGTATCTCGGTGAGATGGAGCCTCCAGCCCTCCCGAGCGAGAAGG                   AGGAGTTTGCCTCGGCCCACTTCTCGCCTGTCCTCAAATGTCTTGCCAGCAGGCTGAG                   CCCAGCCTGGCTGGAGCTGCTGCCCCATGGCCGCCTGGAGGAGCTGTGGGCCAGCTTC                   TTCCTGGAGGGCCCGGCGGACCAAGCCTTCCTGGTGTTGATGGAGACCATCGAGGGTG                   CTGCGGGCCCCAGCTTCCGGCTGATGAAGATGGCGCGGCTGCTGGCCAGATTCCTGCG                   CGAGGGCCGJCTCGCAGTGCTGATGGAGGCGCAGTGTCGGCAGCAGACGCAGCCCGGC                   TTCATCCTGCTCCGGGAGACGCTCCTGGGCAAGGTGGTGGCCCTGCCCGATCACCTGG                   GCAACCGCCTGCAGCACGAGAACTTGGCCGAGTTCTTCCCCCAGAACTACTTCCGCCT                   GCTCGGCGAGGAGCTCGTCCGGGTGCTGCAGGCGGTTGTGGACTCTCTCCAAGGTCCC                   CTGGATTCCTCCGTCTCCTTCGTGTCTCAGGTCCTTGGGAAAGCCTGTGTCCACGGCA                   GGCAGCAGGAGATCCTGGGCGTGCTGGTACCCCGGCTCACAGCGCTCACCCAGGGCAG                   CTACCTGCACCAGCGCGTCTGCTGGCGCCTGGTGGAGCAAGTGCCGGACCGGGCCATG                   GAGGCTGTGCTGACCGGGCTGGTGGAGCCCGCACTGGGGCCTGAGGTCCTTTCGAGAC                   TGCTGGGGAACCTGGTGGTGAAGAACAAGAAGGCCCAGTTTGTGATGACCCAGAAGCT                   TCTGTTCTTACACTCCCGGCTCACGACGCCCATGCTGCAGAGCCTGCTGGGCCATCTG                   CCCATGGACAGCCAGCCGCGCCCGCTCCTGCTGCAGGTGCTGAAGGAGCTGTTGCAGA                   CGTGGGGCAGCAGCAGTGCCATCCGCCACACTCCCCTGCCGCAGCAGCGCCACGTCAG                   CAAGGCTGTCCTCATCTGCCTGGCGCAACTCGGGGAGCCGGAACTGCGGGACAGCCGG                   GATGAACTGCTGGCCAGCATGATGGCGGGCGTGAAGTGCCGCCTGGACAGTAGCCTGC                   CCCCCGTGCGACGCCTCGCCATGATCGTGGCAGAGGTCGTTAGTGCCCGGATCCACCC                   CGAGGGGCCTCCCCTGAAATTCCAGTACGAAGAGGATGAACTGAGCCTCGAGCTGCTG                   GCCTTGGCCTCCCCCCAGCCTGCGGGTGACGGCGCCTCGGAGGCGGGCACGTCCCTCG                   TTCCAGCCACGCCAGAGCCCCCTGCAGAGACCCCCGCAGAGATCGTGGATGGCGGCGT                   CCCCCAAGCACAGCTGGCGGGCTCTGACTCGGACCTGGACAGCGATGATGAGTTTGTC                   CCCTACGACATGTCGGGGGACAGAGAGCTGAAGAGCAGCAAGGCTCCTGCCTACGTCC                   GGGACTGCGTGGAAGCCCTGACCACGTCTGAGGACATAGAGCGCTGTCAGGCAGCCCT                   GCGGGCCCTTGAGGGCCTGGTCTACAGGAGCCCCACAGCCACTCGGGAGGTGAGCGTG                   GAGCTGGCCAAGGTGCTTCTGCATCTGGAGGAGAAGACCTGTCTGGTGGGATTTGCAG                   GGCTGCGCCAGAGAGCCCTGGTGGCCGTCACGGTCACAGACCCGGCCCCCGTGGCCGA                   CTATCTGACCTCACAGTTCTATGCCCTCAACTACAGCCTCCGGCAGCGCATGCACATC                   CTGGATGTGCTGACTCTGGCTGCCCAGGAGCTGTCTAGGCCTGGGTGCCTCGGGAGGA                   CTCCCCAACCTGGCTCCCCAAGTCCCAACACCCCGTCCCTCCCAGAGGCAGCCGTCTC                   TCAGCCTGGCAGTGCCGTGGCGTCTGACTGGCGCCTGGTGCTGGAGGAGCCGATCAGA                   AGCAAGACCCAGCGGCTCTCCAAGGGTGCCCCGAGGCAGGGCCCGGCAGGCAGCCCCA                   GCAGATTCAACTCCGTGGCCGGCCACTTCTTCTTCCCCCTCCTTCAGCGCTTTGACAG                   CCCTCTGGTGACCTTCGACCTCTTGGGAGAAGACCAGCTGGTTCTCGGAAGGCTGGCG                   CACACCTTAGGGGCCCTGATGTGCCTGGCTGTTAACACCACGGTGGCTGTGGCCATGG                   GCAAGGCCCTGCTGGAATTCGTGTGGGCCCTTCGCTTCCACATCGATGCCTACGTGCG                   CCAGGGGCTGTTGTCGGCCGTCTCCTCCGTCCTGCTCAGCCTGCCTGCTGCGCGCCTG                   CTGGAGGACCTGATGGACGAGCTGCTGCAAGCCCGGTCCTGGCTGGCGGACGTGGCTG                   AGAAAGACCCGGACGAGGACTGCAGGACGCTGGCACTGAGGGCCCTGCTGCTTCTGCA                   GAGACTCAAGAACAGGCTCCTCCCACCCGCGTCTCCC TAG   TCCCTGGACCCCTCCCCA                       GGACCACCCTCGCCGACAGCAAGGCAGGCGGCTGAGCAGCGGCCTCCAGCAGCAGAGC                     CAGG                                     ORF Start: ATG at 26   ORE Stop: TAG at 2648           SEQ ID NO:50   874 aa MW at 95583.2 kD                     NOV21a,   MGNRLQRIGGARGLSALQSPGSRVQVVFPGRPDLSCRMEPAPSEVRLAVREAIHALSS               CG95775-01 Protein   SEDGGHIFCTLESLKRYLGEMEPPALPREKEEFASAHFSPVLKCLASRLSPAWLELLP               Sequence   HGRLEELWASFFLEGPADQAFLVLMETIEGAAGPSFRLMKMARLLARFLREGRLAVLM                   EAQCRQQTQPGFILLRETLLGKVVALPDHLGNRLQQENLAEFFPQNYFRLLCEEVVRV                   LQAVVDSLQGGLDSSVSFVSQVLGKACVHGRQQEILGVLVPRLTALTQGSYLHQRVCW                   RLVEQVPDRAMEAVLTGLVEAALGPEVLSRLLGNLVVKNKKAQFVMTQKLLFLQSRLT                   TPMLQSLLGHLAMDSQRRPLLLQVLKELLETWGSSSAIRHTPLPQQRHVSKAVLICLA                   QLGEPELRDSRDELLASMMAGVKCRLDSSLPPVRRLGMIVAEVVSARIHPEGPPLKFQ                   YEEDELSLELLALASPQPAGDGASEAGTSLVPATAEPPAETPAEIVDGGVPQAQLAGS                   DSDLDSDDEFVPYDMSGDRELKSSKAPAYVRDCVEALTTSEDIERCQAALRALEGLVY                   RSPTATREVSVELAKVLLHLEEKTCVVGFAGLRQRALVAVTVTDPAPVADYLTSQFYA                   LNYSLRQRMDILDVLTLAAQELSRPCCLGRTPQPGSPSPNTPCLPEAAVSQPGSAVAS                   DWRVVVEERIRSKTQRLSKGGPRQGPAGSPSRFNSVAGHFFFPLLQRFDRPLVTFDLL                   GEDQLVLGRLAHTLGALMCLAVNTTVAVAMGKALLEFVWALRFHIDAYVRQGLLSAVS                   SVLLSLPAARLLEDLMDELLEARSWLADVAEKDPDEDCRTLALRALLLLQRLKNRLLP                   PASP                  
 
     [0367] 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 plasma membrane; 0.3000       analysis:   probability located in microbody (peroxisome); 0.2000           probability located in endoplasmic reticulum (membrane);           0.1000 probability located in mitochondrial inner membrane       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0368] A search of the NOV21a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 21C.  
               TABLE 21C                          Geneseq Results for NOV21a                                         NOV21a   Identities/                   Residues/   Similarities for           Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value                                             AAU81754   Human clk-2 protein -  Homo sapiens,     38 . . . 874   832/837   (99%)   0.0           836 aa. [WO200198478-A2, 27 DEC.   1 . . . 836   834/837   (99%)           2001]       AAB93337   Human protein sequence SEQ ID   643 . . . 874   226/232   (97%)    e−125           NO:12445 - Homo sapiens, 360 aa.   129 . . . 360   229/232   (98%)           [EP1074617-A2, 07 FEB. 2001]       AAU81758   Mouse clk-2 protein -  Mus musculus,     620 . . . 860   147/241   (60%)   1e−71           350 aa. [WO200198478-A2, 27 DEC.   140 . . . 350   166/241   (67%)           2001]       AAU81755   Partial mouse clk-2 protein #1 -  Mus     336 . . . 488   122/153   (79%)   4e−65             musculus , 153 aa. [WO200198478-A2,   1 . . . 153   142/153   (92%)           27 DEC. 2001]       AAU81759   Partial pig clk-2 protein - Sus scrofa, 122   547 . . . 668   107/122   (87%)   6e−52           aa. [WO200198478-A2, 27 DEC. 2001]   1 . . . 122   111/122   (90%)                  
 
     [0369] In a BLAST search of public sequence datbases, the NOV21a protein was found to have homology to the proteins shown in the BLASTP data in Table 21D.  
               TABLE 21D                          Public BLASTP Results for NOV21a                                         NOV21a   Identities/           Protein       Residues/   Similarities for           Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                             O75168   KIAA0683 PROTEIN -  Homo sapiens     31 . . . 874   840/844   (99%)   0.0           (Human), 844 aa (fragment).   1 . . . 844   842/844   (99%)       Q9BR21   C305C8.3.1 (DFKZP434A073)   38 . . . 874   833/837   (99%)   0.0           (KIAA0683) -  Homo sapiens  (Human),   1 . . . 837   835/837   (99%)           837 aa.       Q9Y4R8   HYPOTHETICAL 91.8 KDA   38 . . . 874   832/837   (99%)   0.0           PROTEIN (KIAA0683 GENE   1 . . . 837   835/837   (99%)           PRODUCT) -  Homo sapiens  (Human),           837 aa.       Q91VQ3   SIMILAR TO RIKEN CDNA   38 . . . 874   627/838   (74%)   0.0           1200003M09 GENE -  Mus musculus     1 . . . 838   703/838   (83%)           (Mouse), 840 aa.       Q9DC40   1200003M09RIK PROTEIN -  Mus     38 . . . 874   626/838   (74%)   0.0             musculus  (Mouse), 840 aa.   1 . . . 838   701/838   (82%)                  
 
     [0370] PFam analysis predicts that the NOV21a protein contains the domains shown in the Table 21E.  
               TABLE 21E                       Domain Analysis of NOV21a                                                        Identities/           Pfam       Similarities   Expect       Domain   NOV21a Match Region   for the Matched Region   Value                  
 
     Example 22  
     [0371] 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:51   1199 bp                     NOV22a,     ATTGATGGGCAGTGCATCTGCGTAACATGGCTACCTCTGAACTCCTTTGGGGAACACG                 CG95942-01 DNA     TATATCTTTGAGAATCCG   ATG AAAACCAGAGATTCCGCCCTTGTTTTCTTACAATTAA               Sequence   AAATATTATCCAGCAATGCAAATGAACAAACTATAACTACACACAGCTGCATGGATAA                   ATGTCAGAAACATGACGTTGAGTGTGAGAAGCCAGATGCAAACGAGGACTCACTGTGC                   AATTCTGTGCATGTACAGTGGCCAGGAGAAGGCAGCACTGGCTTTTCTTTCATCAGCC                   CAAAGATGCCTTTCTTTGCGAATACGTTCAGTCCGAAGAAGACACCTCCTCGGAAGTC                   GGCATCTCTCTCCAACCTGCATTCTTTGGATCGATCAACCCGGGAGGTGGAGCTGGGC                   TTGGAATACGGATCCCCGACTATGAACCTGGCAGGGCAAAGCCTGAAGTTTGAAAATG                   GCCAGTGGATAGCAGACACAGGGGTTAGTGGCGGTGTGGACCGGAGGGAGGTTCAGCG                   CCTTCGCAGGCGGAACCAGCAGTTGGAGGAAGAGAACAATCTCTTGCGGCTGAAAGTG                   GACATCTTATTAGACATGCTTTCAGAGTCCACTGCCGAATCCCACTTAATGGAGAAGG                   AACTGGATGAACTCAGGATCAGCCCCAACAGAA TGA   AGACCCCAGAGACATTTATT                       GGGGAGTAGGATGTGGCTGAGTGCTTTTTTTTTGGCCAGACTAGCGGATTCAGTCCTG                       GAAGAGAGTATCATATAATGAGACCCACACGCACTGGCACCCTTGGGTTGCAATAGA                       AGGTGACATGGAATGGAGAAAACCAAGATTCCAGATGGGGATAGTAACTAGAAGGTGC                       TTCAGATCCACTGCCTGCGGGTGCCAGTCTGAAAACCAGACCCCACACAGGCCTGGGG                       CTGCTGATGAGCTTTTCGGTGCTCTCCACACAACGCTCGCAAACACACATGTCCCAG                       AATAGCTCTGTTGGGTTGTGTTGGGAGAAGCGGCTGGAGTTCATTCTCTCACCCCCTT                       ATGTTGGTGTTTGGCGTGTGACAGCAGTTCTACAGAGCTCTGTGTTCGCGTCTTGGAT                       GAGCGGCTCTCTTGGCTCTTAAAGGCAGGCCTCTCTCTTCTTGCCTCTAAAGAATCCT                       CCTTCCTCACACCTGCCCTCCTCAGTACCTAGACTTAC                                       ORF Start: ATG at 77   ORF Stop: TGA at 674           SEQ ID NO:52   199 aa MW at 22636.3 kD                     NOV22a,   MKTRDSALVFLELKILSSNANEQTITTHSCMDKCQKHDVECEKPDANEDSLCNSVHVQ               Protein   WPGEGSTCFSFIRPKMPFFGNTFSPKKTPPRKSASLSNLHSLDRSTREVELGLEYGSP               Sequence   TMNLAGQSLKFENGQWIAETGVSGGVDRREVQRLRRRNQQLEEENNLLRLKVDILLDM                   LSESTAESHLMEKELDELRISRKRK                  
 
     [0372] Further analysis of the NOV22a protein yielded the following properties shown in Table 22B.  
               TABLE 22B                       Protein Sequence Properties NOV22a                                        PSort   0.5423 probability located in mitochondrial matrix space;       analysis:   0.3000 probability located in microbody (peroxisome); 0.2652           probability located in mitochondrial inner membrane; 0.2652           probability located in mitochondrial intermembrane space       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0373] A search of the NOV22a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 22C.  
               TABLE 22C                          Geneseq Results for NOV22a                                         NOV22a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               AAM00955   Human bone marrow protein, SEQ ID    61 . . . 199   138/139 (99%)   3e−74           NO: 431 -  Homo sapiens , 175 aa.    37 . . . 175   139/139 (99%)           [WO200153453-A2, 26-JUL-2001]       AAY86201   Nuclear transport protein clone hfb2025   133 . . . 199    67/67 (100%)   7e−30           protein sequence -  Homo sapiens ,     1 . . . 67    67/67 (100%)           67 aa. [WO9964455-A1, 16-DEC-1999]       ABB23535   Protein #5534 encoded by probe for    74 . . . 99    26/26 (100%)   3e−08           measuring heart cell gene expression -     1 . . . 26    26/26 (100%)             Homo sapiens , 26 aa.            [WO200157274-A2,           09-AUG-2001]       AAB69070   Human male enhanced antigen-2     92 . . . 193    25/102 (24%)   1.5           (MEA-2) protein sequence SEQ ID    768 . . . 868    45/102 (43%)           NO: 2 -  Homo sapiens ,           1374 aa. [JP2000316580-A,           21-NOV-2000]       AAU36216   Pseudomonas aeruginosa cellular   134 . . . 193    22/67 (32%)   2.6           proliferation protein #206 -    683 . . . 749    35/67 (51%)             Pseudomonas aeruginosa ,           874 aa. [WO200170955-A2,           27-SEP-2001]                  
 
     [0374] 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               Q9Y3M2   HYPOTHETICAL 14.5 KDA     74 . . . 199   126/126 (100%)   5e−66           PROTEIN (CHROMOSOME 22    1 . . . 126   126/126 (100%)           OPEN           READING FRAME 2) -              Homo sapiens  (Human),           126 aa.       AAL56062   CYTOSOLIC LEUCINE-    74 . . . 199   125/126 (99%)   1e−65           RICH PROTEIN -  Homo sapiens      1 . . . 126   126/126 (99%)           (Human), 126           aa.       Q9D1C2   1110014P06RIK PROTEIN (RIKEN    74 . . . 199   104/126 (82%)   2e−56           CDNA 1110014P06 GENE)    1 . . . 126   120/126 (94%)           (CYTOSOLIC LEUCINE-RICH           PROTEIN) -  Mus musculus             (Mouse), 127           aa.       Q9UIK9   HRIHFB2025 PROTEIN -  Homo     133 . . . 199    67/67 (100%)   2e−29           sapiens (Human), 67 aa     1 . . . 67    67/67 (100%)           (fragment).       Q9CVN6   1700121K02RIK PROTEIN -  Mus      77 . . . 190    45/122 (36%)   3e−15             musculus  (Mouse), 226 aa (fragment).    70 . . . 191    69/122 (55%)                  
 
     [0375] PFam analysis predicts that the NOV22a protein contains the domains shown in the Table 22E.  
               TABLE 22E                       Domain Analysis of NOV22a                                                Pfam Domain   NOV22a   Identities/   Expect Value           Match Region   Similarities               for the               Matched Region                  
 
     Example 23  
     [0376] 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:53   717 bp                     NOV23a,     CTGTCGGCGGAGTGGGCGGAGCTGCCGGGGTCAGTTGGTCCAACTGTCCCGCCCTGAG                 CG96211-01 DNA     GTGTCGCCCGGATCCCTCCTTCTCCCGGCGCCTCAAGCGGAAGACCATTCCTCAAGAA                 Sequence     TTTTGTATCCAAGGCCCAAAAGTTTGTTACCCAAG   ATG ATGAATGCTGACATGGATGC                   AGTTGATGCTGAAAATCAAGTGGAACTGGAGGAAAAAACAAGACTTATTAATCAAGTG                   TTGGAACTCCAACACACACTTGAAGATCTCTCTGCAAGAGTACATCCAGTTAAGGAAG                   AAAATCTGAAGCTAAAATCAGAAAACCAAGTTCTTGGACAATATATAGAAAATCTCAT                   GTCAGCTTCTAGTGTTTTTCAAACAACTGACACAAAAAGCAAAAGAAAG TAA   GGGATT                       GACACCCTTCTGTTTTATGGAATTCCTGCTGATCATTTTTTCTTTAAAACTTGCATAG                       ATTCCAAAACTTACAGTACCTTTGTGGCTTCATTGAATATTTATGAAGATAATGTCAG                       ATGTAGACAAAAATAACACAATAACAGGAGACTTCCATAAGTTTGTGTATTATGTTAG                       TCTATGAAAACGTGCAAATGTATTGTAGAGACTTTATGATTAGAATTGCATATATTTA                       TGAAACTTAAAGATGAATGTTTTATTGAATCTGTAGGTTTAGCACTGTCTTTTATTAT                       AGGATTAGTAAGATATACAAG                                       ORF Start: ATG at 152   ORF Stop: TAA at 398           SEQ ID NO:54   82 aa MW at 9354.4 kD                     NOV23a,   MMNADMDAVDAENQVELEEKTRLINQVLELQHTLEDLSARVDAVKEENLKLKSENQVL               CG96211-01 Protein   GQYINLMSASSVFQTTDTKSKRK       Sequence                  
 
     [0377] Further analysis of the NOV23a protein yielded the following properties shown in Table 23B.  
               TABLE 23B                       Protein Sequence Properties NOV23a                                                PSort   0.6500 probability located in cytoplasm;           analysis:   0.1000 probability located in mitochondrial               matrix space; 0.1000 probability located               in lysosome (lumen); 0.0000 probability               located in endoplasmic reticulum (membrane)           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0378] A search of the NOV23a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 23C.  
               TABLE 23C                          Geneseq Results for NOV23a                                         NOV23a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               AAB94677   Human protein sequence SEQ ID    1 . . . 82   82/82 (100%)   2e−39           NO: 15626 -  Homo sapiens , 122 aa.   41 . . . 122   82/82 (100%)           [EP1074617-A2, 07-FEB-2001]       AAY86189   Nuclear transport protein clone hfb2072    1 . . . 82   82/82 (100%)   2e−39           protein sequence -  Homo sapiens , 125 aa.   44 . . . 125   82/82 (100%)           [WO9964455-A1, 16-DEC-1999]       AAB56943   Human prostate cancer antigen protein    1 . . . 82   82/82 (100%)   2e−39           sequence SEQ ID NO: 1521 -  Homo     48 . . . 129   82/82 (100%)             sapiens , 129 aa. [WO200055174-A1,           21-SEP-2000]       AAG00691   Human secreted protein, SEQ ID NO:    1 . . . 81   80/81 (98%)   2e−38           4772 -  Homo sapiens , 139 aa.   41 . . . 121   80/81 (98%)           [EP1033401-A2, 06-SEP-2000]       ABB61942     Drosophila melanogaster  polypeptide   14 . . . 82   52/69 (75%)   3e−22           SEQ ID NO 12618 -    66 . . . 134   60/69 (86%)             Drosophila melanogaster ,           135 aa. [WO200171042-A2,           27-SEP-2001]                  
 
     [0379] 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/                   NOV23a   Similarities       Protein       Residues/   for the       Accession       Match   Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9BZB2   SHORT COILED-COIL PROTEIN     1 . . . 82   82/82 (100%)   4e−39           SCOCO (SHORT COILED COIL     1 . . . 82   82/82 (100%)           PROTEIN) -  Homo sapiens              (Human), 82 aa.       Q96JY9   CDNA FLJ14891 FIS,     1 . . . 82   82/82 (100%)   4e−39           CLONE PLACE1004256,   41 . . . 122   82/82 (100%)           WEAKLY SIMILAR TO             MUS MUSCULUS             SHORT COILED COIL           PROTEIN SCOCO (SCOC) MRNA -             Homo sapiens  (Human),           122 aa.       Q9UIL1   HRIHFB2072 PROTEIN -  Homo sapiens      1 . . . 82   82/82 (100%)   4e−39           (Human), 125 aa (fragment).   44 . . . 125   82/82 (100%)       Q9VB51   CG5934 PROTEIN -  Drosophila     14 . . . 82   52/69 (75%)   8e−22             melanogaster  (Fruit fly), 135 aa.   66 . . . 134   60/69 (86%)       Q9U377   T07C4.10B PROTEIN -  Caenorhabditis     18 . . . 75   44/58 (75%)   2e−18             elegans , 108 aa.   44 . . . 101   55/58 (93%)                  
 
     [0380] 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 Value       Pfam Domain   Match Region   Matched Region               bZIP   31 . . . 71   12/41 (29%)   0.37               28/41 (68%)                  
 
     Example 24  
     [0381] 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:55   1158 bp                     NOV24a,     ATG CCAGACTTCTGTGAACTTGAGTGTGACTGGAAAATCCTTCTGAGGAAAGCACAAG               CG96221-01 DNA   GACTCCTAGAAACCTCTGAGCAAGCAGAGATAGCAGCAGCAGCTCTAACTGTCCTCTT               Sequence   TGCATCTTCTCTTGTTGCCCATCAATCTTCCAGACAGCTGTTTCCAATATGCAAATCG                   AATCATGTCACTCCTTGTTTTGAAAACCATTCAACACTTCCAACTGTGTCGACATGCC                   TAACTAGGCCTTCAGGATCTATGTCACACACCGTCTTCCTGCCCCTTCTTCTCCAGCC                   TTGCCTCTCACCATTCCCCAGTGCCCTTCACCATTTCCCAGTGCCTCTCACCATTCCC                   CAGTGCCCTTCACCATTCCCCAGTGCCCCTCACCATTTCCCAGTGTCCCTCACCATTT                   CCCAGTGCCCCTCACCATTTCCCAGTGCCCTTCACCATTCCCCAGTGCCCTTCACCAT                   TTCCCAGTGCCCTTCACCATTTCCCAGTGCCCTTCACCATTTCCCACTGCCCTTCACC                   ATTTCCCAGTGCCCTTCACCATTTCCCAGTGCCCTTCACCATTTCCCAGTGCCCTTCA                   CCATTCCCCAGTGTCCCTCACCATTTCCCAGTGCCTCTCACCATTCCCCAGTGCCCTT                   CACCATTCCCCAGTGCCTCTCACCATTCCCCACTGCCCTTCACCATTTCCCAGTGCCC                   CTCACCATTCCCCAGTACCCTTCACCATTCCCCAGTGTCCCTCACCATTTCCCAGTGC                   CTCTCACCATTTCCCAGTGCCCTTCACCATTTCCCACTGcccTTcACcATTTCCCAGT                   GCCCTTCACCATTCCCCAGTGTCCCTCACCATTTCCCAGTGCCCTTCACCATTCCCCA                   GTGCCCTTCACCATTTCCCAGTGCCCTTCACCATTCCCCAGTGTCCCTcAcCATTTCC                   CAGTGCCTCTCACCATTCCCCAGTGCCCTTCACCATTCCCCAGTGCCTcTcAcCATTT                   CCCAGTGCCTCTCACCATTTCCCAGTGCCCTTCACCATTTCCCAGTGCTCCTCACCAT                   TTCCCAGTGCCCCTCACCATTTCCCAGTGCCCTTCACCATTCCCCAGTGCCCTTCACC                   ATTCCCCAGTGCCCCTCACCATTTCCCAGTGCCTCTCACCATTCCTCAGTGCC TGA                                       ORF Start: ATG at 1   ORF Stop: TGA at 1156           SEQ ID NO:56   385 aa MW at 41809.8 kD                     NOV24a,   MPDFCELECDWKILLRKAQGLLETSEEAEIAAAALTVLFASSLvAHQSSRELFPICKS               CG96221-01 Protein   NHVTPCFENHSTLPTVSTWLTRPSCSMSHTVFLPLLLQPCLSPFPSALHHFPVPLTIP               Sequence   QCPSPFPSAPHHFPVSLTISQCPSPFPSALHHSPVPFTISQCPSPFPSALHHFPVPFT                   ISQCPSPFPSALHHFPVPFTIPQCPSPFPSASHHSPVPFTIPQCLSPFPSALHHFPVP                   LTIPQYPSPFPSVPHHFPVPLTISQCPSPFPSALHHFPVPFTIPQCPSPFPSALHHSP                   VPFTISQCPSPFPSVPHHFPVPLTIPQCPSPFPSASHHFPVPLTISQCPSPFPSAPHH                   FPVPLTISQCPSPFPSALHHSPVPLTISQCLSPFLSA                  
 
     [0382] Further analysis of the NOV24a protein yielded the following properties shown in Table 24B.  
               TABLE 24B                       Protein Sequence Properties NOV24a                                        PSort   0.6389 probability located in microbody (peroxisome);        analysis:   0.6000 probability located in endoplasmic           reticulum (membrane); 0.1000 probability           located in mitochondrial inner           membrane; 0.1000 probability located in plasma membrane       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0383] A search of the NOV24a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 24C.  
               TABLE 24C                          Geneseq Results for NOV24a                                         NOV24a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               ABG27597   Novel human diagnostic protein   101 . . . 374    89/274 (32%)   1e−30           #27588 -  Homo sapiens ,     38 . . . 311    94/274 (33%)           331 aa. [WO200175067-A2,           11-OCT-2001]       ABG27597   Novel human diagnostic protein   101 . . . 374    89/274 (32%)   1e−30           #27588 -  Homo sapiens ,    38 . . . 311    94/274 (33%)           331 aa. [WO200175067-A2,           11-OCT-2001]       ABG27250   Novel human diagnostic protein    94 . . . 348    95/259 (36%)   2e−15           #27241 -  Homo sapiens ,    13 . . . 206   104/259 (39%)           406 aa. [WO200175067-A2,           11-OCT-2001]       AAM00875   Human bone marrow protein, SEQ ID   119 . . . 367    79/256 (30%)   2e−15           NO: 351 -  Homo sapiens ,    5 . . . 223   109/256 (41%)           243 aa. [WO200153453-A2,           26-JUL-2001]       ABG27250   Novel human diagnostic protein    94 . . . 348    95/259 (36%)   2e−15           #27241 -  Homo sapiens ,    13 . . . 206   104/259 (39%)           406 aa. [WO200175067-A2,           11-OCT-2001]                  
 
     [0384] 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               Q40692   HYDROXYPROLINE-RICH    60 . . . 362    87/324 (26%)   2e−20           GLYCOPROTEIN -  Oryza sativa       68 . . . 369   117/324 (35%)           (Rice), 369 aa.       Q9STN0   EXTENSIN-LIKE PROTEIN -     92 . . . 383    95/327 (29%)   1e−19             Arabidopsis thaliana  (Mouse-ear cress),    8 . . . 318   133/327 (40%)           437 aa.       Q41707   EXTENSIN CLASS 1 PROTEIN   101 . . . 372    87/272 (31%)   3e−19           PRECURSOR (EXTENSIN-LIKE    65 . . . 291   113/272 (40%)           PROTEIN) -  Vigna unguiculata             (Cowpea), 489 aa.       Q9T0K5   EXTENSIN-LIKE PROTEIN -    110 . . . 381    88/275 (32%)   1e−18             Arabidopsis thaliana  (Mouse-ear cress),   476 . . . 734   104/275 (37%)           760 aa.       AAL89866   RE20756P -  Drosophila melanogaster      90 . . . 332    62/249 (24%)   8e−18           (Fruit fly), 285 aa.    46 . . . 279   107/249 (42%)                  
 
     [0385] PFam analysis predicts that the NOV24a protein contains the domains shown in the Table 24E.  
               TABLE 24E                       Domain Analysis of NOV24a                                                Pfam Domain   NOV24a   Identities/   Expect Value           Match Region   Similarities               for the               Matched Region                  
 
     Example 25  
     [0386] 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:57   11947 bp                     NOV25a,     ATGTGCGGTCAGTTCTGAGGCCCTTTGCCTCGTCGAGCCCCACCCTGCCCCAGAGCCC                 CG96394-01 DNA     TGGTCCGAGTGTGCCAGTCATCTGACGCATGCGTGCCTGTTCTTGCCCACAGGTCGTG                 Sequence     CGCGTGGCCAGGGCGCGGGGAC   ATG GGGCCCGACATGGAGCTGCCCAGCCACTCGAAG                   CAGCTCCTGCTCCAGCTGAACCAGCAGAGGACCAAGGGCTTCCTGTGTGACGTCATCA                   TCATGGTGGACAACTCCATCTTCCGGGCCCACAAGAACGTCCTACCCGCCAGCAGCAT                   CTATTTCAAGTCCCTCGTCCTGCACCACAACCTCATCAACCTCGACACACACATGGTC                   AGCTCCACAGTGTTCCAGCAGATCTTGGACTTCATCTACACAGGCAAGCTGCTGCCCA                   GCGACCAGCCAGCCGAGCCCAACTTCAGCACCCTCCTCACTGCCGCCAGCTACCTCCA                   GCTGCCCCAGTTGGCAGCCCTCTGCCGCCGCAAACTCAAGCGAGCCGGCAAGCCCTTT                   GGCTCTGGGAGGGCGGGGTCCACTGGCATAGGGCGGCCCCCCCGCAGCCAGCGGCTGT                   CCACGGCCTCTGTCATCCAAGCTCGGTATCAGGGGCTCGTGGATGGGCGCAAGGGGGC                   CCACGCCCCCCAGGAGCTCCCCCAAGCCAAAGGCTCAGACGATGAACTCTTTCTTGGT                   GGCTCTAACCAGGATAGCGTGCAAGGTCTGGGCCGGGCTGTCTGCCCAGCTGGCGGGG                   AGGCGGGTCTGGGGGGCTGCAGCAGCAGCACCAACGGGAGCAGCGGGGGCTGCGAGCA                   GGAGCTGGCCTTGGACCTGTCCAAGAAAAGCCCACCCTTGCCCCCTGCCACCCCAGGT                   CCCCACCTCACTCCCGATGACGCAGCCCAGCTGAGCGACAGCCAACATGGCTCGCCCC                   CTGCGGCCTCTGCCCCTCCCGTTGCCAACAGTGCCTCTTATTCTGAGCTGGGGGGCAC                   CCCTGATGAGCCCATGGATCTGGACGGCCCCGAGGACAACCACCTGAGCCTGCTGGAG                   GCGCCTGGTGGGCAGCCTCGGAAGAGCCTCCGGCACTCCACTCGGAAGAAGGAGTGGG                   GCAAGAAGGAGCCTGTGGCTGGCTCCCCCTTTGAGCGGAGAGAAGCAGGGCCCAAGGG                   TCCCTGCCCGGGAGAGGAGGGTGAGGGGGTCGGGGACAGGGTTCCCAATGGCATCCTG                   GCTAGTGGGGCTGGCCCTAGCGGGCCCTATGGGGAGCCCCCCTACCCCTGCAAGGAGG                   AGGAGGAGAACGGCAAGGATGCAAGTGAAGACAGTGCGCAGAGCGGGAGCGAGGGGGC                   CAGCGGCCACGCCAGCGCCCACTACATGTACCGGCAGGAGGGCTACGAGACGGTGTCC                   TACGGGGACAACTTGTATGTGTGCATTCCCTGCGCCAAGGGCTTCCCCAGCTCTGAGC                   AGCTCAATCCCCACGTGGAGACTCACACGGAGGAAGAGCTGTTCATCAAGGAAGAGGG                   GGCCTACGAGACAGGCAGTGGGGGTGCCGAGGAGGAGGCCGAGGACCTGTCAGCACCC                   AGTGCGGCCTACACGGCTGAGCCCCGGCCCTTCAAGTGTTCGGTCTGCGAGAAGACCT                   ACAACGACCCAGCCACGCTGCGGCAGCACGAGAAGACGCACTGGCTGACACGGCCCTT                   CCCCTGCAACATCTGTGGCAAAATGTTCACCCACCGCGGCACCATGACGCGTCACATG                   CGGAGCCACCTGGGCCTGAAGCCCTTCGCCTGCGATGAGTGTGGCATGCGCTTCACCC                   GTCAGTACCGCCTCACCCACCACATGCGTGTCCACTCGCGCGAGAAACCTTACCAGTG                   CCAGCTGTCCCCGGGCAAGTTCACCCAGCAGCGCAACCTCATCAGCCACCTGCGCATG                   CACACCTCCCCCTCC TAG   AAGCCAAAGACCCCC                                       ORF Start: ATG at 139   ORF Stop: TAG at 1930           SEQ ID NO: 58   597 aa MW at 64227.0 kD                     NOV25a,   MGPDMELPSHSKQLLLQLNQQRTKGFLCDVILMVENSIFRAHKNVLAASSIYFKSLVL               CG96394-01 Protein   HDNLINLDTDMVSSTVFQQILDFIYTGKLLPSDQPAEPNFSTLLTAASYLQLPELAAL               Sequence   CRRKLKRAGKPFGSGRAGSTGMGRPPRSQRLSTASVIQARYQGLVDGRKGAHAPQELP                   QAKGSDDELFLGGSNQDSVQGLGRAVCPAGCEAGLGGCSSSTNGSSGGCEQELGLDLS                   KKSPPLPPATPGPHLTPDDAAQLSDSQHGSPPAASAPPVANSASYSELGGTPDEPMDL                   EGAEDNHLSLLEAPGGQPRKSLRHSTRKKEWGKKEPVAGSPFERREAGPKGPCPGEEG                   EGVGDRVPNGILASGAGPSGPYGEPPYPCKEEEENGKDASEDSAQSGSEGGSGHASAH                   YMYRQEGYETVSYGDNLYVCIPCAKGPPSSEQLNAHVETHTEEELFIKEEGAYETGSG                   GAEEEAEDLSAPSAAYTAEPRPFKCSVCEKTYKDPATLRQHEKTHWLTRPFPCNICGK                   MFTQRGTMTRHMRSHLGLKPFACDECGMRFTRQYRLTEHMRVHSGEKPYECQLCGGKF                   TQQRNLISULRMHTSPS                  
 
     [0387] Further analysis of the NOV25a protein yielded the following properties shown in Table 25B.  
               TABLE 25B                       Protein Sequence Properties NOV25a                                                PSort   0.4500 probability located in cytoplasm;           analysis:   0.3000 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:                      
 
     [0388] A search of the NOV25a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 25C.  
               TABLE 25C                          Geneseq Results for NOV25a                                         NOV25a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               AAR95242   HIC-1 polypeptide -  Homo sapiens , 547    401 . . . 593   131/203 (64%)   3e−70           aa. [WO9614877-A1, 23-MAY-1996]    231 . . . 428   148/203 (72%)       AAG66311   Human zinc finger protein 46 -  Homo      371 . . . 594    78/224 (34%)   3e−34             sapiens , 419 aa. [WO200155188-A1,    140 . . . 335   113/224 (49%)           02-AUG-2001]       ABG01726   Novel human diagnostic protein #1717 -     371 . . . 594    81/225 (36%)   1e−33             Homo sapiens , 1342 aa.   1034 . . . 1229   113/225 (50%)           [WO200175067-A2, 11-OCT-2001]       ABG01726   Novel human diagnostic protein #1717 -     371 . . . 594    81/225 (36%)   1e−33             Homo sapiens , 1342 aa.   1034 . . . 1229   113/225 (50%)           [WO200175067-A2, 11-OCT-2001]       ABG07279   Novel human diagnostic protein #7270 -     373 . . . 594    74/222 (33%)   1e−33             Homo sapiens , 792 aa. [WO200175067-    246 . . . 456   111/222 (49%)           A2, 11-OCT-2001]                  
 
     [0389] In a BLAST search of public sequence datbases, the NOV25a protein was found to have homology to the proteins shown in the BLASTP data in Table 25D.  
               TABLE 25D                          Public BLASTP Results for NOV25a                                         NOV25a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96JB3   HIC-3 -  Homo sapiens  (Human), 597    1 . . . 597   595/597 (99%)   0.0           aa.    1 . . . 597   595/597 (99%)       Q9UPX9   KIAA1020 PROTEIN -  Homo sapiens      43 . . . 597   554/555 (99%)   0.0           (Human), 555 aa (fragment).    1 . . . 555   555/555 (99%)       Q9NSM9   HYPOTHETICAL 34.7 KDA   283 . . . 597   315/315 (100%)   0.0           PROTEIN -  Homo sapiens  (Human),    1 . . . 315   315/315 (100%)           315 aa (fragment).       Q90W33   HRG22 PROTEIN -  Brachydanio rerio      5 . . . 597   348/602 (57%)   e−172           (Zebrafish) (Zebra danio), 560 aa.    1 . . . 560   412/602 (67%)       Q9JLZ6   HYPERMETHYLATED IN CANCER   338 . . . 597   241/263 (91%)   e−147           2 PROTEIN -  Mus musculus  (Mouse),    4 . . . 266   246/263 (92%)           266 aa (fragment).                  
 
     [0390] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25E.  
               TABLE 25E                          Domain Analysis of NOV25a                                     Identities/                   Similarities           NOV25a   for the Matched       Pfam Domain   Match Region   Region   Expect Value               K_tetra    37 . . . 122   20/115 (17%)   0.58               52/115 (45%)       BTB    12 . . . 125   44/143 (31%)   1.6e−22               86/143 (60%)       zf-C2H2   487 . . . 509    8/24 (33%)   1.5e−05               21/24 (88%)       zf-C2H2   515 . . . 537    9/24 (38%)   3.9e−07               22/24 (92%)       zf-C2H2   543 . . . 565    9/24 (38%)   1.3e−05               19/24 (79%)       zf-C2H2   571 . . . 593   11/24 (46%)   0.00014               19/24 (79%)                  
 
     Example 26  
     [0391] 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:59   365 bp                     NOV26a,     CACGTGCACCCACTGCCTCTTCCCTTCTCGCTTGGGAACTCTAGTCTCGCCTCGGGTT                 CG96470-01 DNA     GCA   ATG GACCCCAACTGCTCCTGTGCCGCTGCAGGTGTCTCCTGCACCTGCGCCAGCT               Sequence   CCTGCAAGTGCAAAGAGTGCAAATGCACCTCCTGCATCTGCAAAGGGGCATCGGAGAA                   GTGCAGCTGCTCCGCC TGA   TGTCGCGACAGCCCTGCTCCCAAGTACAAATAGAGTGAC                       CCGTAAAATCCAGGATTTTTTGTTTTTTCCTACAATCTTGACCCCTTTGCTACATTCC                       TTTTTTTCTGTGAAATATGTGAATAATAATTAAACACTTAGACTTGAAAAAAAAAAAA                       AAAAAAAAACCAAAAAA                                       ORF Start: ATG at 62   ORF Stop: TGA at 191           SEQ ID NO:60   43 aa MW at 4279.9 kD                     NOV26a,   MDPNCSCAAAGVSCTCASSCKCKECKCTSCICKGASEKCSCCA       CG96470-01 Protein       Sequence                  
 
     [0392] Further analysis of the NOV26a protein yielded the following properties shown in Table 26B.  
               TABLE 26B                       Protein Sequence Properties NOV26a                                                PSort   0.7963 probability located in mitochondrial           analysis:   intermembrane space; 0.4785 probability               located in mitochondrial matrix space;               0.4500 probability located in cytoplasm; 0.1852               probability located in mitochondrial inner membrane           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0393] 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                                             Identities/                   NOV26a   Similarities               Residues/   for the       Geneseq   Protein/Organism/Length [Patent #,   Match   Matched   Expect       Identifier   Date]   Residues   Region   Value               AAU14784   Novel bone marrow polypeptide #183 -     1 . . . 43   43/62 (69%)   2e−19             Homo sapiens , 98 aa. [WO200157187-A2,   37 . . . 98   43/62 (69%)           09-AUG-2001]       AAO13869   Human polypeptide SEQ ID NO 27761 -     1 . . . 42   39/61 (63%)   2e−16             Homo sapiens , 89 aa. [WO200164835-A2,   29 . . . 88   40/61 (64%)           07-SEP-2001]       AAB56852   Human prostate cancer antigen protein    1 . . . 42   39/61 (63%)   2e−16           sequence SEQ ID NO: 1430 -  Homo     35 . . . 94   40/61 (64%)             sapiens , 95 aa. [WO200055174-A1,           21-SEP-2000]       AAM78488   Human protein SEQ ID NO 1150 -  Homo      1 . . . 43   38/62 (61%)   5e−16             sapiens , 117 aa. [WO200157190-A2,   57 . . . 117   39/62 (62%)           09-AUG-2001]       AAB57183   Human prostate cancer antigen protein    1 . . . 43   38/62 (61%)   5e−16           sequence SEQ ID NO: 1761 -  Homo      9 . . . 69   39/62 (62%)             sapiens , 69 aa. [WO200055174-A1,           21-SEP-2000]                  
 
     [0394] 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               P80296   Metallothionein-IK (MT-1K) -  Homo     1 . . . 43   43/62 (69%)   4e−19             sapiens  (Human), 62 aa.   1 . . . 62   43/62 (69%)       P13640   Metallothionein-IG (MT-1G) -  Homo     1 . . . 43   42/62 (67%)   3e−17             sapiens  (Human), 61 aa.   1 . . . 61   42/62 (67%)       P80295   Metallothionein-II (MT-1I) -  Homo     1 . . . 43   41/62 (66%)   1e−16             sapiens  (Human), 61 aa.   1 . . . 61   41/62 (66%)       P04733   Metallothionein-IF (MT-1F)   1 . . . 42   39/61 (63%)   4e−16           (HQP0376) -  Homo sapiens  (Human),   1 . . . 60   40/61 (64%)           61 aa.       P18055   Metallothionein-IIA (MT-2A) -    1 . . . 43   38/62 (61%)   4e−16             Oryctolagus cuniculus  (Rabbit), 62 aa.   1 . . . 62   40/62 (64%)                  
 
     [0395] PFam analysis predicts that the NOV26a protein contains the domains shown in the Table 26E.  
               TABLE 26E                          Domain Analysis of NOV26a                                     Identities/                   Similarities           NOV26a   for the        Pfam Domain   Match Region   Matched Region   Expect Value               metalthio   1 . . . 43   36/68 (53%)   0.011               41/68 (60%)                  
 
     Example 27  
     [0396] 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:61   258 bp                     NOV27a,     TTTTAGGAA   ATG TGTTCTAGCTGCAGTGCAGACAGTGTGGAGATACAGCAGCCCAAGG               CG96650-01 DNA   GAATGACCCACAGGAGGCTAGTGCAATTGTCTAGTGGCTGTGGGGTGGGGGGCATGTT               Sequence   GAGGGGGATGGGGCTGGCCACATGGGGTGAAGGAAGAAGGAGCTGGTCCTGGGTTCCT                   GGCCCGTGTGACTGTGTCAGCTGGTGGCTCTGC TAA   TGGCACAGAGAACACAGGAGTA                       GGCAAGCTGCTGGATGAGCAGAGCTT                               ORF Start: ATG at 10   ORF Stop: TAA at 208       SEQ ID NO: 62   66 aa MW at 7176.2 kD                     NOV27a,   MCSSCSADSVEIQQPKGMTHRRLVQLSSGCGVGGMLRGMGLATWGEGRRSWSWVPGPC               CG96650-01 Protein   DCVSWWLC       Sequence                  
 
     [0397] Further analysis of the NOV27a protein yielded the following properties shown in Table 27B.  
               TABLE 27B                       Protein Sequence Properties NOV27a                                                PSort   0.6400 probability located in microbody           analysis:   (peroxisome); 0.4500 probability               located in cytoplasm; 0.1000 probability               located in mitochondrial matrix space;                0.1000 probability located               in lysosome (lumen)           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0398] A search of the NOV27a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 27C.  
               TABLE 27C                          Geneseq Results for NOV27a                                             Identities/                   NOV27a   Similarities                   Residues/   for the           Geneseq   Protein/Organism/Length [Patent #,   Match   Matched   Expect       Identifier   Date]   Residues   Region   Value                                         AAY04948   Mycobacterium species protein sequence   22 . . . 58   15/37 (40%)   2.4           41B - Mycobacterium sp, 92 aa.   48 . . . 82   19/37 (50%)           [WO9909186-A2, 25 Feb. 1999]       AAY32375   Mouse CNREB-2 transcription factor -   31 . . . 57   13/27 (48%)   6.9             Mus musculus , 763 aa. [WO9955343-A1,   70 . . . 92   15/27 (55%)           04 Nov. 1999]       ABB12321   Human carcinogenesis inhibitor   11 . . . 63   18/55 (32%)   9.1           homologue, SEQ ID NO: 2691 -  Homo     126 . . . 178   26/55 (46%)             sapiens , 1685 aa. [WO200157188-A2, 09           Aug. 2001]                  
 
     [0399] 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                                         Q9ZVQ8   PUTATIVE PHLOEM-SPECIFIC   35 . . . 57   11/24 (45%)   9.1           LECTIN -  Arabidopsis thaliana  (Mouse-   132 . . . 155   14/24 (57%)           ear cress), 305 aa.                  
 
     [0400] PFam analysis predicts that the NOV27a protein contains the domains shown in the Table 27E.  
               TABLE 27E                          Domain Analysis of NOV27a                                     Identities/                   Similarities                   for the   Expect       Pfam Domain   NOV27a Match Region   Matched Region   Value                  
 
     Example 28  
     [0401] 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:63   544 bp                     NOV28a,     GAGGGGAAAGCCCAGGGGTACAGGAGGCCTCTGGGTGAAGGCAGAGGCTAAC   ATG GGG               CG96682-01 DNA   TTCGGAGCGACCTTGGCCGTTGGCCTGACCATCTTTGTGCTGTCTGTCGTCACTATCA               Sequence   TCATCTGCTTCACCTGCTCCTGCTGCTGCCTTTACAAGACGTGCCGCCGACCACGTCC                   GGTTGTCACCACCACCACATCCACCACTGTGGTGCATGCCCCTTATCCTCAGCCTCCA                   AGTGTGCCGCCCAGCTACCCTGGACCAAGCTACCAGGGCTACCACACCATGCCGCCTC                   AGCCACGGATGCCAGCAGCACCCTACCCAATGCAGTACCCACCACCTTACCCAGCCCA                   GCCCATGGGCCCACCGGCCTACCACGAGACCCTGGCTGTTGATATGAGACTGAAACCC                   CTGGGTTGTGGAGGGAAATTGGCTCAGAGATGGACAACCTGGCAACTG TG   AGTCCCTG                       CTTCCCGACACCAGCCTCATGGAATATGCAACAACTCCTGTACCCCAGTCCACGGTGT                       TCTGGCAGCAGGGACCCTGGGC                                       ORF Start: ATG at 53   ORF Stop: TGA at 455           SEQ ID NO:64   134 aa MW at 14570.0 kD                     NOV28a,   MGFGATLAVGLTIFVLSVVTIIICFTCSCCCLYKTCRRPRPVVTTTTSTTVVHAPYPQ               CG96682-01 Protein   PPSVPPSYPGPSYQGYHTMPPQPGMPAAPYPMQYPPPYPAQPMGPPAYHETLAVDMRL               Sequence   KPLGCGGKLAQRWTTWQL                  
 
     [0402] Further analysis of the NOV28a protein yielded the following properties shown in Table 28B.  
               TABLE 28B                       Protein Sequence Properties NOV28a                                        PSort   0.8200 probability located in endoplasmic reticulum (mem-       analysis:   brane); 0.1900 probability located in plasma membrane;           0.1000 probability located in endoplasmic reticulum (lumen);           0.1000 probability located in outside       SignalP   Cleavage site between residues 32 and 33       analysis:                  
 
     [0403] 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               AAB31675   Amino acid sequence of a human protein   1 . . . 111   111/111 (100%)   5e−66           having a hydrophobic domain -  Homo     1 . . . 111   111/111 (100%)             sapiens , 137 aa. [WO200104297-A2, 18           Jan. 2001]       AAM39215   Human polypeptide SEQ ID NO 2360 -   1 . . . 111   111/111 (100%)   5e−66             Homo sapiens , 137 aa. [WO200153312-   1 . . . 111   111/111 (100%)           A1, 26 Jul. 2001]       AAY84606   A human small proline-rich molecule   1 . . . 111   111/111 (100%)   5e−66           (HSPRM) polypeptide -  Homo sapiens ,   1 . . . 111   111/111 (100%)           137 aa. [WO200018924-A1, 06 Apr.           2000]       AAY59678   Secreted protein 108-008-5-0-E6-FL -   1 . . . 111   111/111 (100%)   5e−66             Homo sapiens , 137 aa. [WO9940189-A2,   1 . . . 111   111/111 (100%)           12 Aug. 1999]       AAW75087   Human secreted protein encoded by gene   1 . . . 111   111/111 (100%)   5e−66           31 clone HTHBA79 -  Homo sapiens , 155   1 . . . 111   111/111 (100%)           aa. [WO9839446-A2, 11 Sep. 1998]                  
 
     [0404] 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 NOV28a                                         NOV28a   Identities/           Protein       Residues/   Similarities for           Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                             CAC28408   SEQUENCE 28 FROM PATENT   1 . . . 111   111/111   (100%)   1e−65           WO0104297 -  Homo sapiens  (Human),   1 . . . 111   111/111   (100%)           137 aa.       CAC39754   SEQUENCE 145 FROM PATENT   2 . . . 111   110/110   (100%)   5e−65           EP1067182 -  Homo sapiens  (Human),   105 . . . 214    110/110   (100%)           240 aa.       Q96MW8   CDNA FLJ31766 FIS, CLONE   2 . . . 111   110/110   (100%)   5e−65           NT2RI2007879, WEAKLY SIMILAR   74 . . . 183    110/110   (100%)           TO HOMEOBOX PROTEIN HOX-A4 -             Homo sapiens  (Human), 209 aa.       Q9CQP5   6430628I05RIK PROTEIN (RIKEN   1 . . . 111   88/113   (77%)   2e−50           CDNA 6430628I05 GENE) -  Mus     1 . . . 113   96/113   (84%)             musculus  (Mouse), 132 aa.       Q91Z37   RIKEN CDNA 2310008D10 GENE -   2 . . . 111   87/112   (77%)   9e−50             Mus musculus  (Mouse), 236 aa.   106 . . . 217    95/112   (84%)                  
 
     [0405] PFam analysis predicts that the NOV28a protein contains the domains shown in the Table 28E.  
               TABLE 28E                          Domain Analysis of NOV28a                                     Identities/                   Similarities                   for the    Expect       Pfam Domain   NOV28a Match Region   Matched Region   Value                  
 
     Example 29  
     [0406] 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:65   718 bp                     NOV29a,     GGCGCGTGGTCTACGCCGAGTGACAGAGACGCTCAGGCTGTGTTCTCAGG   ATG ACCGA               CG96704-01 DNA   GTGGGAGACAGCAGCACCAGCGGTGGCAGAGACCCCAGACATCAAGCTCTTTGGGAAG               Sequence   TGGAGCACCGATCATGTGCAGATCAATGACATTTCCCTGCAGGATTACATTGCAGTGA                   AGGAGAAGTATGCCAAGTACCTGCCTCACAGTGCAGGGCGGTATGCCGCCAAACGCTT                   CCGCAAAGCTCAGTGTCCCATTGTGGAGCGCCTCACTAACTCCATGATGATGCACGGC                   CGCAACAACGGCAAGAAGCTCATGACTGTGCGCATCGTCAAGCATGCCTTCGAGATCA                   TACACCTGCTCACAGGCGAGAACCCTCTGCAGGTCCTGGTGAACGCCATCATCAACAG                   TGGTCCCCGGGAGGACTCCACACGCATTGGGCGCGCCGGGACTGTGAGACGACAGGCT                   GTGGATGTGTCCCCCCTGCGCCGTGTGAACCAGGCCATCTGGCTGCTGTGCACAGGCG                   CTCGTGAGGCTGCCTTCCGGAACATTAAGACCATTGCTGAGTGCCTGGCAGATGAGCT                   CATCAATGCTGCCAAGGGCTCCTCGAACTCCTATGCCATTAAGAAGAAGGACGAGCTG                   GAGCGTGTGGCCAAGTCCAACCGC TGA   TTTTCCAGCTGCTGCCCAATAAACCTGTCTG                       CCCTTTGCGATCCCAGCCAAAA                                       ORF Start: ATG at 51   ORF Stop: TGA at 663           SEQ ID NO:66   204 aa MW at 22876.1 kD                     NOV29a,   MTEWETAAPAVAETPDIKLFGKWSTDDVQINDISLQDYIAVKEKYAKYLPHSAGRYAA               CG96704-01 Protein   KRFRKAQCPIVERLTNSMMMHGRNNGKKLMTVRIVKHAFEIIHLLTGENPLQVLVNAI               Sequence   INSGPREDSTRIGRAGTVRRQAVDVSPLRRVNQAIWLLCTGAREAAFRNIKTIAECLA                   DELINAAKGSSNSYAIKKKDELERVAKSNR                             SEQ ID NO:67   702 bp                     NOV29b,     GGTCTACGCCGAGTGACAGAGACGCTCAGGCTGTGTTCTCAGG   ATG ACCGAGTGGGAG               CG96704-02 DNA   ACAGCAGCACCAGCGGTGGCAGAGACCCCAGACATCAAGCTCTTTGGGAAGTGGAGCA               Sequence   CCGATGATGTGCAGATCAATGACATTTCCCTGCAGGATTACATTGCAGTGAAGGAGAA                   GTATGCCAAGTACCTGCCTCACAGTGCAGGGCGGTATGCCGCCAAACGCTTCCGCAAA                   GCTCAGTGTCCCATTGTGGAGCGCCTCACTAACTCCATGATGATGCACGGCCGCAACA                   ACGGCAAGAAGCTCATGACTGTGCGCATCGTCAAGCATGCCTTCGAGATCATACACCT                   GCTCACAGGCGAGAACCCTCTGCAGGTCCTGGTGAACGCCATCATCAACAGTGGTCCC                   CGCGAGGACTCCACACGCATTGGGCGCGCCGGCACTGTGAGACGACAGGCTGTGGATG                   TGTCCCCCCTGCGCCGTGTGAACCAGGCCATCTGGCTGCTGTGCACAGGCCCTCGTGA                   GGCTGCCTTCCGGAACATTAAGACCATTGCTGAGTGCCTGGCAGATGAGCTCATCAAT                   GCTGCCAAGGGCTCCTCGAACTCCTATGCCATTAAGAAGAAGGACGAGCTGGAGCGTG                   TGGCCAAGTCCAACCGC TGA   TTTTCCCAGCTGCTGCCCAATAAACCTGTCTCCCCTTT                       GGGATC                                       ORF Start: ATG at 44   ORF Stop: TGA at 656           SEQ ID NO:68   204 aa MW at 22876.1 kD                     NOV29b,   MTEWETAAPAVAETPDIKLFGKWSTDDVQINDISLQDYIAVKEKYAKYLPHSAGRYAA               CG96704-02 Protein   KRFRKAQCPIVERLTNSMMMHGRNNGKKLMTVRIVKHAFEIIHLLTCENPLQVLVNAI               Sequence   INSGPREDSTRIGRAGTVRRQAVDVSPLRRVNQAIWLLCTGAREAAFRNIKTIAECLA                   DELINAAKGSSNSYAIKKKDELERVAKSNR                  
 
     [0407] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 29B.  
               TABLE 29B                          Comparison of NOV29a against NOV29b.                         Protein   NOV29a Residues/   Identities/       Sequence   Match Residues   Similarities for the Matched Region               NOV29b   1 . . . 204   204/204 (100%)           1 . . . 204   204/204 (100%)                  
 
     [0408] Further analysis of the NOV29a protein yielded the following properties shown in Table 29C.  
               TABLE 29C                       Protein Sequence Properties NOV29a                                        PSort   0.6500 probability located in cytoplasm; 0.1642 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:                  
 
     [0409] A search of the NOV29a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 29D.  
               TABLE 29D                          Geneseq Results for NOV29a                                         NOV29a   Identities/                   Residues/   Similarities for           Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               ABB64077     Drosophila melanogaster  polypeptide    5 . . . 204   177/200 (88%)   1e−98           SEQ ID NO 19023 -  Drosophila     29 . . . 228   188/200 (93%)             melanogaster , 228 aa. [WO200171042-           A2, 27 Sep. 2001]       ABG15625   Novel human diagnostic protein #15616 -   27 . . . 204   178/178 (100%)   2e−97             Homo sapiens , 178 aa. [WO200175067-    1 . . . 178   178/178 (100%)           A2, 11 Oct. 2001]       ABG15625   Novel human diagnostic protein #15616 -   27 . . . 204   178/178 (100%)   2e−97             Homo sapiens , 178 aa. [WO200175067-    1 . . . 178   178/178 (100%)           A2, 11 Oct. 2001]       ABB62878     Drosophila melanogaster  polypeptide    8 . . . 204   171/197 (86%)   3e−96           SEQ ID NO 15426 -  Drosophila     34 . . . 230   185/197 (93%)             melanogaster , 230 aa. [WO200171042-           A2, 27 Sep. 2001]       AAG43178     Arabidopsis thaliana  protein fragment   14 . . . 204   152/192 (79%)   2e−84           SEQ ID NO: 53937 -  Arabidopsis     16 . . . 207   174/192 (90%)             thaliana , 207 aa. [EP1033405-A2, 06           Sep. 2000]                  
 
     [0410] In a BLAST search of public sequence datbases, the NOV29a protein was found to have homology to the proteins shown in the BLASTP data in Table 29E.  
               TABLE 29E                          Public BLASTP Results for NOV29a                                         NOV29a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96BN0   RIBOSOMAL PROTEIN S5 -  Homo sapiens     1 . . . 204    204/204 (100%)   e−113           (Human), 204 aa.   1 . . . 204    204/204 (100%)       Q91V55   0 DAY NEONATE THYMUS CDNA,   1 . . . 204   202/204 (99%)   e−112           RIKEN FULL-LENGTH ENRICHED   1 . . . 204   202/204 (99%)           LIBRARY, CLONE:A430101M19, FULL           INSERT SEQUENCE (ADULT MALE           KIDNEY CDNA, RIKEN FULL-LENGTH           ENRICHED LIBRARY,           CLONE:0610006D06, FULL INSERT           SEQUENCE) (ADULT MALE TONGUE           CDNA, RIKEN FULL-LENGTH           ENRICHED LIBRARY,           CLONE:2310037J07, FULL INSERT           SEQUENCE) (ES CELLS CDNA, RIKEN           FULL-LENGTH ENRICHED LIBRARY,           CLONE:2410046E20, FULL INSERT           SEQUENCE) (11 DAYS EMBRYO CDNA,           RIKEN FULL-LENGTH ENRICHED           LIBRARY, CLONE:2700054J16, FULL           INSERT SEQUENCE) (11 DAYS           EMBRYO CDNA, RIKEN FULL-LENGTH           ENRICHED LIBRARY,           CLONE:2700063O13, FULL INSERT           SEQUENCE) (12 DAYS EMBRYO           EMBRYONIC BODY BETWEEN           DIAPHRAGM REGION AND NECK           CDNA, RIKEN FULL-LENGTH           ENRICHED LIBRARY,           CLONE:9430066A13, FULL INSERT           SEQUENCE) -  Mus musculus  (Mouse), 204           aa.       P46782   40S ribosomal protein S5 -  Homo sapiens     1 . . . 204   202/204 (99%)   e−112           (Human), 204 aa.   1 . . . 204   202/204 (99%)       P97461   40S ribosomal protein S5 -  Mus musculus     1 . . . 204   201/204 (98%)   e−112           (Mouse), 204 aa.   1 . . . 204   201/204 (98%)       P24050   40S ribosomal protein S5 -  Rattus norvegicus     1 . . . 204   200/204 (98%)   e−111           (Rat), 204 aa.   1 . . . 204   200/204 (98%)                  
 
     [0411] PFam analysis predicts that the NOV29a protein contains the domains shown in the Table 29F.  
               TABLE 29F                          Domain Analysis of NOV29a                                     Identities/               NOV29a Match   Similarities   Expect       Pfam Domain   Region   for the Matched Region   Value               Ribosomal_S7   51 . . . 204   66/165 (40%)   9.3e−71               140/165 (85%)                   
 
     Example 30  
     [0412] 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:69   1908 bp                     NOV30a,     ACAGGTGACTTTTCCACAGGAACTTCTGCA   ATG TCCCATCAACCTCTCAGCTGCTGGA               CG97090-01 DNA   ATTCGCCCTTATCCTCCCACCTGGATCTCCCAAACCTGGACACATTTACCCCGGAGGA               Sequence   GCTGCTGCAGCAGATGAAAGAGCTCCTGACCGAGAACCACCAGCTGAAAGAAGCCATG                   AAGCTAAATAATCAAGCCATGAAAGGGAGATTTGAGGAGCTTTCGGCCTGGACAGAGA                   AACAGAAGGAAGAACGCCAGTTTTTTGAGATACAGAGCAAAGAAGCAAAAGAGCGTCT                   AATGGCCTTGAGTCATGAGAATGAGAAATTGAAGGAAGAGCTTGGAAAACTAAAAGGG                   AAATCAGAAAGGTCATCTGAGGACCCCACTGATGACTCCAGGCTTCCCAGGGCCGAAG                   CGGAGCAGGAAAAGGACCAGCTCAGGACCCAGGTGGTGAGGCTACAACCACAGAAGGC                   AGACCTGTTGGGCATCGTGTCTGAACTGCAGCTCAAGCTGAACTCCAGCGGCTCCTCA                   GAAGATTCCTTTGTTGAAATTAGGATGGCTGAAGGAGAAGCAGAAGGGTCAGTAAAAG                   AAATCAAGCATAGTCCTGGGCCCACGAGAACAGTCTCCACTGGCACGAGCAGATCTGC                   AGATGGGGCCAAGAATTACTTCGAACATGAGGAGTTAACTGTGAGCCAGCTCCTGCTG                   TGCCTAAGGGAAGGGAATCAGAAGGTGGAGAGACTTGAAGTTGCACTCAAGGAGGCCA                   AAGAAAGAGTTTCAGATTTTGAAAAGAAAACAAGTAATCGTTCTGAGATTGAAACCCA                   GACACAGGGGAGCACAGAGAAAGAGAATGATGAAGAGAAAGGCCCGGAGACTGTTGGA                   AGCGAAGTGGAAGCACTGAACCTCCAGGTGACATCTCTGTTTAAGGAGCTTCAAGAGG                   CTCATACAAAACTCAGCGAAGCTGAGCTAATGAAGAAGAGACTTCAAGAAAAGTGTCA                   GGCCCTTGAAAGGAAAAATTCTGCAATTCCATCAGAGTTGAATGAAAAGCAAGAGCTT                   GTTTATACTAACAAAAAGTTAGAGCTACAAGTGGAAAGCATGCTATCAGAAATCAAAA                   TGGAACAGCCTAAAACAGAGGATGAAAAGTCCAAATTAACTGTGCTACAGATGACACA                   CAACAAGCTTCTTCAACAACATAATAATGCATTGAAAACAATTGAGGAACTAACAAGA                   AAAGAGTCAGAAAAAGTGGACAGGGCAGTGCTGAAGGAACTGAGTGAAAAACTGGAAC                   TGGCAGAGAAGGCTCTGGCTTCCAAACAGCTGCAAATGGATGAAATGAAGCAAACCAT                   TGCCAAGCAGGAAGAGGACCTGGAAACCATGACCATCCTCAGGGCTCAGATGGAAGTT                   TACTGTTCTGATTTTCATGCTGAAAGAGCAGCGAGAGAGAAAATTCATGAGGAAAAGG                   AGCAACTGGCATTGCAGCTGGCAGTTCTGCTGAAAGAGAATGATGCTTTCGAAGACGG                   AGGCAGGCAGTCCTTGATGGAGATGCAGAGTCCTCATGGGGCGAGAACAAGTGACTCT                   GACCAGCAGGCTTACCTTGTTCAAAGAGGAGCTGAGGACAGGGACTGGCGGCAACAGC                   GGAATATTCCGATTCATTCCTGCCCCAAGTGTGGAGAGGTTCTGCCTGACATAGACAC                   GTTACAGATTCACGTGATGGATTGCATCATT TAA   GTGTTGATGTATCACCTCCCCAAA                       ACTGTTGGTAAATGTCAGATTTTTTCCTCCAAGAGTTGTGCTTTTGTGTTATTTGTTT                       TCACTCAAATATTTTGCCTCATTATTCTTGTTTTAAAAGAAAGAAAACAGGCCGGGCA                       CAGTGGCTCATGCCTGTAATCCCAGCACTTTGGGAGATCCAGGTGGGAGGAT                                       ORF Start: ATG at 31   ORF Stop: TAA at 1714           SEQ ID NO:70   561 aa MW at 64267.6 kD                     NOV30a,   MSHQPLSCWNSPLSSHLDLPNLDTFTPEELLQQMKELLTENHQLKEAMKLNNQANKGR               CG97090-01 Protein   FEELSAWTEKQKEERQFFEIQSKEAKERLMALSHENEKLKEELGKLKGKSERSSEDPT               Sequence   DDSRLPRAEAEQEKDQLRTQVVRLQAEKADLLGIVSELQLKLNSSGSSEDSFVEIRMA                   EGEAEGSVKEIKHSPGPTRTVSTGTSRSADGAKNYFEHEELTVSQLLLCLREGNQKVE                   RLEVALKEAKERVSDFEKKTSNRSEIETQTEGSTEKENDEEKGPETVGSEVEALNLQV                   TSLFKELQEAHTKLSEAELMKKRLQEKCQALERKNSAIPSELNEKQELVYTNKKLELQ                   VESMLSEIKMEQAKTEDEKSKLTVLQMTHNKLLQEHNNALKTIEELTRKESEKVDRAV                   LKELSEKLELAEKALASKQLQMDEMKQTIAKQEEDLETMTILRAQMEVYCSDFHAERA                   AREKIHEEKEQLALQLAVLLKENDAFEDGCRQSLMEMQSRHGARTSDSDQQAYLVQRG                   AEDRDWRQQRNIPIHSCPKCGEVLPDIDTLQINVMDCII                                     SEQ ID NO:71   1908 bp                     NOV30b,     ACAGGTGACTTTTCCACAGGAACTTCTGCA   ATG TCCCATCAACCTCTCAGATCCTCCC               CG97090-02 DNA   ACCTGGATCTCCCAAACCTGGACACGTTTACCCCGGAGGAGCTGCTGCAGCAGATGAA               Sequence   AGAGCTCCTGACCGACAACCACCAGCTGAAAGAAGCCATGAAGCTAAATAATCAAGCC                   ATGAAAGGGAGATTTGAGGAGCTTTCGGCCTGGACAGAGAAACAGAACGAAGAACGCC                   AGTTTTTTGAGATACAGAGCAAAGAAGCAAAAGAGCGTCTAATGGCCTTGAGTCATGA                   GAATGAGAAATTGAAGGAAGAGCTTGGAAAACTAAAAGGGAAATCAGAAAGGTCATCT                   GAGGACCCCACTGATGACTCCAGGCTTCCCACGGCCGAAGCGGAGCAGGAAAAGGACC                   AGCTCAGGACCCAGGTGGTGAGGCTACAAGCAGAGAAGGCAGACCTGTTGGGCATCGT                   GTCTGAACTGCAGCTCAAGCTGAACTCCAGCGGCTCCTCAGAAGATTCCTTTGTTGAA                   ATTAGGATGGCTGAAGGAGAAGCAGAAGGGTCAGTAAAAGAAATCAAGCATAGTCCTG                   GGCCCACGAGAACAGTCTCCACTGGCACGGCATTGTCTAAATATAGGACCAGATCTGC                   AGATGGGGCCAAGAATTACTTCGAACATGAGGAGTTAACTGTGAGCCAGCTCCTGCTG                   TGCCTAAGGGAAGGGAATCAGAAGGTGGAGAGACTTGAAGTTGCACTCAAGGAGGCCA                   AAGAAAGAGTTTCAGATTTTGAAAAGAAAACAAGTAATCGTTCTGAGATTGAAACCCA                   GACAGAGGGGAGCACAGAGAAAGAGAATGATGAAGAGAAAGGCCCGGAGACTGTTGGA                   AGCGAAGTGGAAGCACTGAACCTCCAGGTGACATCTCTGTTTAAGGAGCTTCAAGAGG                   CTCATACAAAACTCAGCGAAGCTGAGCTAATGAAGAAGAGACTTCAAGAAAAGTGTCA                   GGCCCTTGAAAGGAAAAATTCTGCAATTCCATCAGAGTTGAATGAAAAGCAAGAGCTT                   GTTTATACTAACAAAAAGTTAGAGCTACAAGTGGAAAGCATGCTATCACAAATCAAAA                   TGGAACAGGCTAAAACAGAGGATGAAAAGTCCAAATTAACTGTGCTACAGATGACACA                   CAACAAGCTTCTTCAAGAACATAATAATGCATTGAAAACAATTGAGGAACTAACAAGA                   AAAGAGTCACAAAAAGTGGACAGGGCAGTGCTGAAGGAACTGAGTGAAAAACTGGAAC                   TCGCAGAGAAGGCTCTGGCTTCCAAACAGCTGCAAATGOATGAAATGAAGCAAACCAT                   TGCCAAGCAGGAAGAGGACCTGGAAACCATGACCATCCTCAGGGCTCAGATGGAAGTT                   TACTGTTCTGATTTTCATGCTGAAACAGCAGCGAGAGAGAAAATTCATGAGGAAAAGG                   AGCAACTGGCATTGCAGCTGGCAGTTCTGCTGAAAGAGAATGATGCTTTCGAAGACGG                   AGGCAGGCAGTCCTTGATGGAGATGCAGAGTCGTCATGGGGCGAGAACAAOTGACTCT                   GACCAGCAGGCTTACCTTGTTCAAAGAGGAGCTGAGGACAGGGACTGGCGGCAACAGC                   GGAATATTCCGATTCATTCCTGCCCCAAGTGTGCACAGCTTCTGCCTGACATAGACAC                   GTTACAGATTCACGTGATGGATTGCATCATTTAAGTGT TAA   TGTATCACCTCCCCAAA                       ACTGTTGGTAAATGTCAGATTTTTTCCTCCAAGAGTTGTGCTTTTGTGTTATTTGTTT                       TCACTCAAATATTTTGCCTCATTATTCTTGTTTTAAAAGAAAGAAAACAGGCCGGGCA                       CAGTGGCTCATGCCTGTAATCCCAGCACTTTGGGAGATCCAGGTGGGAGGAT                                       ORF Start: ATG at 31   ORF Stop: TAA at 1714           SEQ ID NO:72   561 aa MW at 64354.8 kD                     NOV30b,   MSHQPLRSSHLDLPNLDTFTPEELLQQMKELLTENHQLKEAMKLNNQAMKGRFEELSA               CG97090-02 Protein   WTEKQKEERQFFEIQSKEAKERLMALSHENEKLKEELGKLKGKSERSSEDPTDDSRLP               Sequence   RAEAEQEKDQLRTQVVRLQAEKADLLGIVSELQLKLMSSGSSEDSPIEIRMAEGEAEG                   SVKEIKHSPGPTRTVSTGTALSKYRSRSADGAKNYFEHEELTVSQLLLCLREGNQKVE                   RLEVALKEAKERVSDFEKKTSNRSEIETQTEGSTEKENDEEKGPETVGSEVEALNLQV                   TSLFKELQEAHTKLSEAELMKKRLQEKCQALERKNSAIPSELNEKQELVYTNKKLELQ                   VESMLSEIKMEQAKTEDEKSKLTVLQMTHNKLLQEHNNALKTIEELTRKESEKVDRAV                   LKELSEKLELAEKALLASKQLQMDEMKQTIAKQEEDLETMTILRAQMEVYCSDFHAERA                   AREKIHEEKEQLALQLAVLLKENDAFEDGGRQSLMEMQSRHGARTSDSDQQAYLVQRG                   AEDRDWRQQRNIPIHSCPKCGEVLPDIDTLQIHVMDCII                  
 
     [0413] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 30B.  
               TABLE 30B                          Comparison of NOV30a against NOV30b.                                 Identities/           NOV30a Residues/   Similarities for       Protein Sequence   Match Residues   the Matched Region               NOV30b   1 . . . 561   520/567 (91%)           1 . . . 561   520/567 (91%)                  
 
     [0414] Further analysis of the NOV30a protein yielded the following properties shown in Table 30C.  
               TABLE 30C                       Protein Sequence Properties NOV30a                                        PSort   0.4500 probability located in cytoplasm; 0.3000 probability located in microbody       analysis:   (peroxisome); 0.1000 probability located in mitochondrial matrix space; 0.1000           probability located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0415] A search of the NOV30a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 30D.  
               TABLE 30D                          Geneseq Results for NOV30a                                         NOV30a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               AAY27431   Murine RIP-associated protein (RAP-2)   232 . . . 560   100/341 (29%)   3e−33           splice variant (NEMO full) - Mus sp, 412    90 . . . 412   184/341 (53%)           aa. [WO9947672-A1, 23 Sep. 1999]       AAY27430   Human RIP-associated protein (RAP-2) -   229 . . . 558   101/337 (29%)   6e−32             Homo sapiens , 416 aa. [WO9947672-A1,    88 . . . 416   184/337 (53%)           23 Sep. 1999]       ABG06505   Novel human diagnostic protein #6496 -    29 . . . 487   117/511 (22%)   2e−15             Homo sapiens , 2633 aa. [WO200175067-   1054 . . . 1546   230/511 (44%)           A2, 11 Oct. 2001]       ABG06505   Novel human diagnostic protein #6496 -    29 . . . 487   117/511 (22%)   2e−15             Homo sapiens , 2633 aa. [WO200175067-   1054 . . . 1546   230/511 (44%)           A2, 11 Oct. 2001]       AAM41000   Human polypeptide SEQ ID NO 5931-    22 . . . 502   126/563 (22%)   2e−15             Homo sapiens , 1988 aa. [WO200153312-    983 . . . 1526   236/563 (41%)           A1, 26 Jul. 2001]                  
 
     [0416] 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 30E.  
               TABLE 30E                          Public BLASTP Results for NOV30a                                             Identities/                   NOV30a   Similarities       Protein       Residues/   for the       Accession       Match   Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96CV9   TUMOR NECROSIS FACTOR ALPHA-   1 . . . 561   555/577 (96%)   0.0           INDUCIBLE CELLULAR PROTEIN   1 . . . 577   556/577 (96%)           CONTAINING LEUCINE ZIPPER           DOMAINS, HUNTINGTIN INTERACTING           PROTEIN L, TRANSCRPTION FACTOR           IIIA-INTERACTING PROTEIN -  Homo               sapiens  (Human), 577 aa.       Q9Y218   FIP2 - Homo sapiens (Human), 577 aa.   1 . . . 561   552/577 (95%)   0.0               1 . . . 577   554/577 (95%)       Q9BGR3   HYPOTHETICAL 65.1 KDA PROTEIN -   1 . . . 561   538/571 (94%)   0.0             Macaca fascicularis  (Crab eating macaque)   1 . . . 571   547/571 (95%)           (Cynomolgus monkey), 571 aa.       Q95KA2   HYPOTHETICAL 62.9 KDA PROTEIN -   16 . . . 561    526/546 (96%)   0.0             Macaca fascicularis  (Crab eating macaque)   5 . . . 550   534/546 (97%)           (Cynomolgus monkey), 550 aa.       Q9UET9   FIP2 -  Homo sapiens  (Human), 520 aa.   48 . . . 561    511/520 (98%)   0.0               1 . . . 520   512/520 (98%)                  
 
     [0417] PFam analysis predicts that the NOV30a protein contains the domains shown in the Table 30F.  
               TABLE 30F                          Domain Analysis of NOV30a                                             Identities/                   NOV30a   Similarities           Pfam   Match   for the   Expect           Domain   Region   Matched Region   Value                       zf-C2H2   537 . . . 559   6/24 (25%)   0.51                   17/24 (71%)                       
 
     Example 31  
     [0418] 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   589 bp                     NOV31a,     CTCCTTGCTTCTTTCCAGCCGGAGCCGCTGCCTTGCCCCCCGGAGACTGAAGAC   ATG G               CG97134-01 DNA   CACCCAAGAGGGCCAAGAGAAGGACAGTAGAGGGCGGAAGCTCCAGCGTCTTCTCCAT               Sequence   GTTCGACCAGACTCAGATCCAGGAGTTCAAAGAGGCCTTCACTGTGATCGACCAGAAC                   CGTGATGGTATTATAGACAAGGAGGACCTTCGGGACACCTTCGCAGCCATGGGCCGCC                   TCAATGTGAAGAATGAGGAGTTGGATGCCATGATGAAGGAAGCCAGCGGTCCCATCAA                   CTTCACCGTCTTCCTGACCATGTTCGGGGAGAAGCTCAAGGGTGCCGACCCTGAGGAT                   GTGATCACCGGAGCCTTCAAGGTCTTGGACCCTGAGGGAAAGGGCACCATCAAGAAGA                   AGTTCCTGGAGGAGCTGCTGACCACGCAGTGTGACCGCTTCTCCCAGGAGGAGATCAA                   GAACATGTGGGCGGCCTTCCCCCCCGACGTGGGCGGCAACGTCGACTACAAAAACATC                   TGCTACGTCATCACGCACGGCGACGCCAAGGACCAGGAG TAG   GGGCACCCGCGGGCCT                       CCGCTGCCG                                       ORF Start: ATG at 55   OPT Stop: TAG at 562           SEQ ID NO:74   169 aa MW at 19014.4 kD                     NOV31a,   MAPKRAKRRTVEGGSSSVFSMFDQTQIQEFKEAFTVIDQNRDGIIDKEDLRDTFAAMG               CG97134-01 Protein   RLNVKNEELDAMMKEASGPINFTVFLTMFGEKLKGADPEDVITGAFKVLDPEGKGTIK               Sequence   KKFLEELLTTQCDRFSQEEIKNMWAAFPPDVGGNVDYKNICYVITHGDAKDQE                  
 
     [0419] Further analysis of the NOV31a protein yielded the following properties shown in Table 31B.  
               TABLE 31B                       Protein Sequence Properties NOV31a                                        PSort   0.4820 probability located in mitochondrial matrix space; 0.2723 probability located in       analysis:   microbody (peroxisome); 0.1907 probability located in mitochondrial inner membrane;           0.1907 probability located in mitochondrial intermembrane space       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0420] 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 [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               AAB08483   Fast skeletal muscle isoform of the   1 . . . 168   137/169 (81%)   1e−77           myosin light chain 2 -  Danio rerio , 169   1 . . . 169   156/169 (92%)           aa. [WO200049150-A1, 24 Aug. 2000]       AAR05422   Human ventricular myosin light chain 2   1 . . . 167   119/167 (71%)   5e−66           protein -  Homo sapiens , 165 aa.   1 . . . 165   144/167 (85%)           [EP357856-A, 14 Mar. 1990]       AAU14245   Human novel protein #116 -  Homo     1 . . . 168   101/175 (57%)   4e−54             sapiens , 173 aa. [WO200155437-A2, 02   1 . . . 173   136/175 (77%)           Aug. 2001]       AAM78885   Human protein SEQ ID NO 1547 -  Homo     1 . . . 169    96/172 (55%)   3e−46             sapiens , 171 aa. [WO200157190-A2, 09   1 . . . 170   121/172 (69%)           Aug. 2001]       AAO13875   Human polypeptide SEQ ID NO 27767 -   1 . . . 169    95/173 (54%)   6e−45             Homo sapiens , 204 aa. [WO200164835-   33 . . . 203    118/173 (67%)           A2, 07 Sep. 2001]                  
 
     [0421] 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               Q96A32   MYOSIN REGULATORY LIGHT   1 . . . 169    169/169 (100%)   1e−94           CHAIN 2 (UNKNOWN) (PROTEIN   1 . . . 169    169/169 (100%)           FOR MGC:13450) -  Homo sapiens             (Human), 169aa.       Q14843   MYOSIN LIGHT CHAIN 2 -  Homo     1 . . . 169   169/170 (99%)   3e−93             sapiens (Human), 170 aa.   1 . . . 170   169/170 (99%)       MORBLD   myosin L2 (DTNB) regulatory light   1 . . . 169   164/170 (96%)   5e−91           chain, skeletal muscle - rabbit, 170 aa.   1 . . . 170   167/170 (97%)       MORTL2   myosin L2 (DTNB) regulatory light   1 . . . 169   162/169 (95%)   9e−91           chain precursor, skeletal muscle - rat,   1 . . . 169   165/169 (96%)           169aa.       Q28710   MYOSIN LIGHT CHAIN 2 -   1 . . . 169   163/170 (95%)   2e−90             Oryctolagus cuniculus  (Rabbit), 170 aa.   1 . . . 170   167/170 (97%)                  
 
     [0422] PFam analysis predicts that the NOV31a protein contains the domains shown in the Table 31E.  
               TABLE 31E                          Domain Analysis of NOV31a                                 NOV31a    Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               efhand   29 . . . 57   10/29 (34%)   8.7e−05               26/29 (90%)                  
 
     Example 32  
     [0423] 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   384 bp                     NOV32a,     GGGAAA   ATG GCTGCGTCTTCGAGTGGTGAGAAGGAGAAGGAGCGGCTGGGAGGCGGTT               CG97219-01 DNA   TGGGAGTGGCGGGTGGTAACAGCACACGAGAGCGGCTGCTGTCTGCGCTTGAGGACTT               Sequence   GGAGGTCCTGTCTAGGGAACTTATAGAAATGCTGGCAATTTCAAGAAACCAAAAGTTG                   TTACAGGCTGGAGAGGAAAACCAGGTCCTGGAGTTGTTAATTCACCGAGATGGGGAATT                   TTCAAGAACTAATGAAATTGGCACTTAATCAGGGAAAAATTCATCATGAAATGCAAGT                   TTTAGAAAAAGAAGTAGAGAAGAGAGACAGTGATATTCAGTATTTGTTCTGCTTCCTT                     TAG   CTGTTTTTGTAGCTGCTGAATATCACTGTCTCT                                       ORF Start: ATG at 7   ORF Stop: TAG at 349           SEQ ID NO:76   114 aa MW at 12851.5 kD                     NOV32a,   MAASSSGEKEKERLGGGLGVAGGNSTRERLLSALEDLEVLSRELIEMLAISRNQKLLQ               CG97219-01 Protein   AGEENQVLELLTHRDGEFQELMKLALNQGKIHHEMQVLEKEVEKRDSDIQYLFCFL       Sequence                  
 
     [0424] Further analysis of the NOV32a protein yielded the following properties shown in Table 32B.  
               TABLE 32B                       Protein Sequence Properties NOV32a                                        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:                  
 
     [0425] A search of the NOV32a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 32C.  
               TABLE 32C                          Geneseq Results for NOV32a                                         NOV32a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               AAB93477   Human protein sequence SEQ ID   1 . . . 110   109/110 (99%)   3e−54           NO: 12759 -  Homo sapiens , 270 aa.   1 . . . 110   109/110 (99%)           [EP1074617-A2, 07-FEB-2001]       AAM40946   Human polypeptide SEQ ID NO 5877 -   1 . . . 110   109/110 (99%)   3e−54             Homo sapiens , 249 aa. [WO200153312-   6 . . . 115   109/110 (99%)           A1, 26-JUL-2001]       AAM39160   Human polypeptide SEQ ID NO 2305 -   1 . . . 110   109/110 (99%)   3e−54             Homo sapiens , 270 aa. [WO200153312-   1 . . . 110   109/110 (99%)           A1, 26-JUL-2001]       AAG01268   Human secreted protein, SEQ ID NO:    1 . . . 87      87/87 (100%)   2e−41           5349 -  Homo sapiens , 87 aa. [EP1033401-   1 . . . 87      87/87 (100%)           A2, 06-SEP-2000]       ABB60687   Drosophila melanogaster polypeptide   25 . . . 110     33/86 (38%)   1e−08           SEQ ID NO 8853 -  Drosophila     6 . . . 86     56/86 (64%)             melanogaster , 258 aa. [WO200171042-           A2, 27-SEP-2001]                  
 
     [0426] 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               Q9NYR5   P36 TRAP/SMCC/PC2 SUBUNIT -   1 . . . 110   109/110 (99%)   7e−54             Homo sapiens  (Human), 270 aa.   1 . . . 110   109/110 (99%)       Q9NPJ6   VITAMIN D RECEPTOR-   1 . . . 110   109/110 (99%)   7e−54           INTERACTING PROTEIN COMPLEX   1 . . . 110   109/110 (99%)           COMPONENT DRIP36 -  Homo sapiens             (Human), 270 aa.       Q9BS95   HSPC126 PROTEIN -  Homo sapiens     1 . . . 110   108/110 (98%)   2e−53           (Human), 270 aa.   1 . . . 110   108/110 (98%)       Q9CQA5   2410046H15RIK PROTEIN -  Mus     1 . . . 110    98/110 (89%)   3e−47             musculus  (Mouse), 270 aa.   1 . . . 110   102/110 (92%)       Q9VS38   CG8609 PROTEIN (LD46084P) -   25 . . . 110     33/86 (38%)   3e−08             Drosophila melanogaster  (Fruit fly), 258   6 . . . 86     56/86 (64%)           aa.                  
 
     [0427] PFam analysis predicts that the NOV32a protein contains the domains shown in the Table 32E.  
               TABLE 32E                       Domain Analysis of NOV32a                                                    NOV32a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value                  
 
     Example 33  
     [0428] 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   2315 bp                     NOV33a,     TCCGCGCGGCCCCGGCACAAGCAGCCA   ATG AACACGCGGCTGCGCCCGGCCTCGCGCC               CG97358-01 DNA   TCCATTGGCTGCGCCCCGCCACCCGCTGCCCCGCAGGTTCCCAAGCCGGGTTTAAAGG               Sequence   GTCCCAGGCGCGCGTGAACGCGGTCCCCGGGACCATGCTGCGGCCACAGCGGCCCGGA                   GACTTGCAGCTCGGGGCCTCCCTCTACGAGCTGGTGGGCTACAGGCAGCCGCCCTCCT                   CCTCCTCCTCCTCCACCTCCTCCACCTCCTCCACTTCCTCCTCCTCCACGACGGCCCC                   CCTCCTCCCCAAGGCTGCGCGCGAGAAGCCGGAGGCGCCGGCCGAGCCTCCAGGCCCC                   GGGCCCGGGTCAGGCGCGCACCCGGGCGGCAGCGCCCGGCCGGACGCCAAGGAGGAGC                   AGCAGCAGCAGCTGCGGCGCAAGATCAACAGCCGCGAGCGGAAGCGCATGCAGGACCT                   GAACCTGGCCATGGACGCCCTGCGCGAGGTCATCCTGCCCTACTCAGCGGCGCACTGC                   CAGGGCGCGCCCGGCCGCAAGCTCTCCAAGATAGCCACGCTGCTGCTCGCCCGCAACT                   ACATCCTACTGCTGGGCAGCTCGCTGCAGGAGCTGCGCCGCGCGCTGGGCGAGGGCGC                   CGGGCCCGCCGCGCCGCGCCTGCTGCTGGCCGGGCTGCCCCTGCTCGCCGCCGCGCCC                   GGCTCCGTGCTGCTGGCGCCCGGCGCCGTAGGACCCCCCGACGCGCTGCGCCCCGCCA                   AGTACCTGTCGCTGGCGCTGGACGAGCCGCCGTGCGGCCAGTTCGCTCTCCCCGGCGG                   CGGCGCAGGCGGCCCCGGCCTCTGCACCTGCGCCGTGTGCAAGTTCCCGCACCTGGTC                   CCGGCCAGCCTGGGCCTGGCCGCCGTGCAGGCGCAATTCTCCAAG TGA   GGGCGGGCCT                       GGGCCTGGGGCGCGACCTCGGCCCGGCCTCCCTTCGCTCAGCTTCTCCGCGCCCCTGC                       TCCCTGCGTCTGGGAGAGCGAGGCCGAGCAAGGAAAGCATTTCGAACCTTCCAGTCCA                       GAGGAAGGGACTGTCGGGCACCCCCTTCCCCGCCCCCACCCCTGGGACGTTAAAGTGA                       CCAGAGCGGATGTTCGATGGCGCCTCGGGGCAGTTTGGGGTTCTGGGTCGGTTCCAGC                       GGCTTTAGGCAGAAAGTGCTCGCTCTCACCCAGCACATCTCTCTCCTTGTCCCTGGAG                       TTGCGCGCTTCGCGGGGCCGATGTAGAACTTAGGGCGCCTTGCCGTGGTTGGCGCGCC                       CCGGGTGCAGCGAGAGGCCATCCCCGAGCGCTACCTCCCCGGAGCGGAGCACGCCGGC                       TCCCAGTACTAGGGGCTGCGCTCGAGCAGTGGCGGGGGCGGAGGGGTGGTTCTTTTCC                       TTCTCCTCCGCCAGAGGCCACGGGCGCCCTTGTTCCCGCCGGCCAGGTCCTATCAAAG                       GAGGCTGCCGGAACTCAAGAGGCAGAAAAAGACCAGTTAGGCGGTGCAGACGGTCTGG                       GACGTGGCAGACGGACGGACCCTCGGCGGACAGGTGGTCGGCGTCGGGGTGCGGTGGG                       TAGGGGCGAGGACAACGCAGGGTGCGCTGGGTTGGGACGTGGGTCCACTTTTGTAGAC                       CAGCTGTTTGGAGAGCTGTATTTAAGACTCGCGTATCCAGTGTTTTGTCGCAGAGAGT                       TTTCGCTCTTAAATCCTGGGGGTTTCTTAGAAAGCAACTTAGAACTCGAGATTCACCT                       TTCGTTTCCCTTTCCCCAAAAGTAGCGTAACCAACATTTAAGCTTGCTTAAAAACGAA                       AACCAACCGCCTTGCATCCAGTGTTCCCGATTTACTAAAATAGGTAACCAGGCGTCTC                       ACAGTCGCCGTCCTGTCAAGAGCGCTAATGAACGTTCTCATTAACACGCAGGAGTACC                       GGGAGCCCTGAACCGCCCGCTGCTCGGCGGATCCCAGCTGCGGTGGCGACGGCGGGAA                       GGCGCTTTCCGCTGTTCCTCAGCGGGCCGGGCCCTTGACCAGCGCGGCCCGCAGGTCT                       TCCTTCTCGCCGTCTTGCAGTTGAAGAGCTACATACGTAGTCAGTTTCGATTTGTTAC                       AGACGTTAACAAATTCCTTTACCCAAGGTTATGCTATGACCTTTCCGCAGTTTACTTT                       GATTTTCTATGTTTAAGGTTTTGGTTGTTGGTAGTAGCCGAATTTAACTGGCACTTTA                       TTTTACTTCTAACCTTGTTTCCTGACGGTGTACAGAATCAACAAAATAAAACATTTAA                       AGTCTGATTTTTTACATTTTTTGTCTGATTTGTTTGGTAATAAAAAAGTCCTT                                       ORF Start: ATG at 28   ORF Stop: TGA at 916           SEQ ID NO:78   296 aa MW at 30595.7 kD                     NOV33a,   MNTRLRPASRLHWLRPATRCPAGSQAGFKGSQARVNAVPGTMLRPQRPGDLQLGASLY               CG97358-01 Protein   ELVGYRQPPSSSSSSTSSTSSTSSSSTTAPLLPKAAREKPEAPAEPPGPGPGSGAHPG               Sequence   GSARPDAKEEQQQQLRRKINSRERKRMQDLNLANDALREVILPYSAAHCQGAPGRKLS                   KIATLLLARNYILLLGSSLQELRRALGEGAGPAAPRLLLAGLPLLAAAPGSVLLAPGA                   VGPPDALRPAKYLSLALDEPPCGQFALPGGGAGGPGLCTCAVCKFPHLVPASLGLAAV                   QAQFSK                  
 
     [0429] Further analysis of the NOV33a protein yielded the following properties shown in Table 33B.  
               TABLE 33B                       Protein Sequence Properties NOV33a                                        PSort   0.7163 probability located in mitochondrial inner membrane;       analysis:   0.4732 probability located in mitochondrial matrix space;           0.4732 probability located in mitochondrial           intermembrane space; 0.4732 probability           located in mitochondrial outer membrane       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0430] A search of the NOV33a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 33C.  
               TABLE 33C                          Geneseq Results for NOV33a                                         NOV33a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               ABB61621   Drosophila melanogaster polypeptide   37 . . . 236   80/203 (39%)   1e−16           SEQ ID NO 11655 -  Drosophila     42 . . . 228   101/203 (49%)              melanogaster , 232 aa. [WO200171042-           A2, 27-SEP-2001]       AAB60357   Chicken atonal homologue ngn2/ath4a   82 . . . 260   63/192 (32%)   5e−10           protein, SEQ ID NO: 21 -  Gallus gallus ,   22 . . . 206   84/192 (42%)           213 aa. [WO200073764-A2, 07-DEC-2000]       AAY70566   Murine neurogenin-1 (NGN1) protein -   68 . . . 267   66/221 (29%)   2e−09           Mus sp, 244 aa. [WO200009676-A2, 24-FEB-2000]   15 . . . 209   85/221 (37%)       AAW54944   Mouse neurogenin 1 protein - Mus sp,   68 . . . 267   66/221 (29%)   2e−09           244 aa. [WO9813491-A2, 02-APR-1998]   15 . . . 209   85/221 (37%)       AAW71019   Murine neuroD3 protein, which is a   68 . . . 267   66/221 (29%)   2e−09           bHLH protein -  Mus musculus , 244 aa.   15 . . . 209   85/221 (37%)           [US5795723-A, 18-AUG-1998]                  
 
     [0431] 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               Q9WUQ3   OLG-1 BHLH PROTEIN -  Rattus     42 . . . 296   225/257 (87%)    e−118             norvegicus  (Rat), 245 aa.    1 . . . 245   230/257 (88%)       Q9JKN5   OLIGODENDROCYTE-SPECIFIC   42 . . . 296   222/257 (86%)    e−116           BHLH TRANSCRIPTION FACTOR    1 . . . 244   228/257 (88%)           OLIG1 (OLIG1 BHLH PROTEIN) -  Mus               musculus  (Mouse), 244 aa.       Q9NZ14   BASIC HELIX-LOOP-HELIX PROTEIN   68 . . . 278   102/297 (34%)   2e−23            CLASS B 1 -  Homo sapiens  (Human), 357   60 . . . 335   124/297 (41%)           aa (fragment).       Q13516   Protein kinase C-binding protein RACK17   68 . . . 278   102/297 (34%)   2e−23            (Protein kinase C binding protein 2) -   37 . . . 312   124/297 (41%)             Homo sapiens  (Human), 334 aa           (fragment).       Q90XB3   BHLH TRANSCRIPTION FACTOR   74 . . . 290    96/256 (37%)   4e−23            OLIG2 -  Gallus gallus  (Chicken), 298 aa.   40 . . . 290   124/256 (47%)                  
 
     [0432] PFam analysis predicts that the NOV33a protein contains the domains shown in the Table 33E.  
               TABLE 33E                          Domain Analysis of NOV33a                                 NOV33a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               HLH   131 . . . 190   23/62 (37%)   2.6e−09               39/62 (63%)                  
 
     Example 34  
     [0433] 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   3390 bp                     NOV34a,     ATTCAAATAGAAATGCAAAGGGTGACACTCCTATTTGGCAGCCATTTCTCTTAAAGCT                 CG97378-01 DNA     CAGTGGTTCTGGACCTGCAGTATCTGCTGAGTTAGGAGGGACAGGAGAGTAGCAGCTA                 Sequence     GGTCGGTGGCAAATAGCCCGCAACATTCCCTTTAGTTACA   ATG AGTTTACCCCTCAAT                   CTCAAATATTTCCTCAGTGGATTAACAGGAGAGCCAGTGATGGTGAAGCTTAAGTGGG                   GAATGGAGTATAACGGCTACCTGGTATCTGTAGATGGCTATATGAACATGCAGCTTGC                   AGATACAGAATTCATAAATGAGGCATTGCCTGGACATCTAGGTGAAGTTTTAATAAGG                   TGTAATAATGTCCTTTATATCACAGATGTGCAAGAAGAGGAAATGGGGAAA TGA   GTGA                       ATAGCATCTTTTGAAGAGGATTTTTTAAATATGTATTTCTAGACAATAAAGATTTGTT                       TTTCAAAAAAAAAAAAAAGCAAAGGGCCTGGAGTAACAAAAACCATTTTGAAAAAGAAC                       AAAGTAATTTCAAGACTCACTATAAAGTTACAGTAATCAAGGCAGTGTGGTATTTATG                       TAAGCACAGAGATACAGATCAATGAAACAGAATACAGGGTCCAGAAATAGATCCATCT                       ACATGGTCAACTGAAATTTGAAAAATATGTCAAAATTACTCAATGGAGAAAGGATAGT                       CTTTTCAACAATTGAATATCCATGTGCAAAAATATGAAGCTTAACCCTTGCCCTCATA                       ACACATACAAAGGTTAACTCAGAGTCAATGACAAGACTTAAATGTCAGAGCTAAAACT                       ACAAAACTTCTAGAAGTAAACATAAACAAAAATATTCATGACTTTGTTAGGGAAAAAC                       TTCTAAGACCTTTGGAAAAGCATGGACCATAGAAGAAAAAATTGATAAACTGAACTTC                       TGCAAAATTAAAAAAATTCTGCTCCCCAAATTACATAATTTAAAAAATAAAAAGGCAA                       GCCACAGACTGGGAGAAATATTTGCAAAATATAAAGGACTTATATCTAGAATATGTTT                       TTAAAGACACACACACATACACAAATCCATATAAATACTAACAATTTGGCTTAAAAAA                       AAGGACAAAAGATTTGAACAGACACTTGACTGAACAAGGTATTTATCAATGCAAATAA                       ACATGTGGAAAGATGCTCCATATCATTAAACACCAAGGAAATGCAAATTTACACCAAA                       ATAAGATGCCACTAGAATAGCTAAACTTAAAAAGACTTACAATATCAAGTGTTGGCAA                       GGATGTGGAGCAACTGGAGCTCATACGCTGCTGCCAAGTAGTATAGCCACTTTGGAAA                       ACTGTTTGGGAGTTTCTTATATAATTAGATATATACTTACCATATGATCCAGCAGTCT                       CACTCCTGGATTTATCAAAAAGCAATGAAATCATATGTCCACTCAAACGCTTGTACTC                       AACAGTTCATACAACCTTTATTCATAATAGACACAAATTTATATGTGCTTATATATGT                       ATATGTTTATATGTTTATATATGTAGTCATGTTTATATAACTACACATATTTATCAAA                       ACTCATTGAATTCATACTTAAACAAGCCAACTGTTTATTATCTAGTAAATGAACAAAT                       AGTGGTATAATTATACAATGAAATACTACTCAGCCATGAAAAGGAATGGACTACTGAT                       ACACTCAACAGAAGGAATGGACTGCAGAGACACTCAACAGCACAGATGAATCTCAAAA                       GCATTACAGTAAACAAGCCCACCACAGAAGGGTCCATGCTOTACATCCGATACCATTT                       TTCTCAAATTCTAGAAGAGCTAAAAGTGTTGAAAGCAGATCAAAGGCCAGACGTGGTG                       GCTCACACCTGCAATCCCAGCATGTTGGGAGGCCAAAACAGCCAGATCTCTTGAGCCC                       AGAAGTTCAAGACTAGCCTGGGCAACATGCCAAAACCTTATCTCTACTAAAAATACAA                       AAAAAAAAAAAAAAGCAAAAACAAAAACAAAAACAAAAAACAAAAAACCAGCTGGGTG                       TGGTCGCACACAGCTGTAGTCCCAGCTACTCAGGAGGCTGAGGTGGGACCATCACCTG                       AACCCAGGGAGATAAGGCTGCAGTGAGCCGTGATCACACCACTACACTCCAGCCTGGG                       TGACAGTAAGACCCTGTCTGTCAAAAAAAAAAAAAAAAGACAAAGAAAAGAAAAGCAA                       TGGCTGCCAAAAGCTGGAGGTTCGGAAGGGGACCGAATACAAAAGAACATAAGGGAAC                       TTTCTGGGTGATGGAAATGATCCATATTTTGATAGTGGTGGTGTTTATATGACTACAC                       GTGTTTATCAAAACTCATTGAATTCATACTTAAAATGAGTGAAACTTATTCTAAATTA                       TACTTTAATAAGTTAATAAAAAACAAGAAGTGGGTTGGGGAGACGTTGCTCAAAGGAT                       ACAAACTTTCAGTGAGGAGGAATAAGTTCAAGAGATCTACTGTACAACACGGTGACCA                       TAGTCAATAACAATGTATTATATTCTTGCAAATTGGCCAGGTGAGGTGGCTCACACCT                       GTAATCTCAACACTTTGGGAGGCAGGAGGAACACTCAAGCCTAGGACTTCAAGACCAG                       CCTGGGCAATATAGGGAGATCTCGCCCCTACAGATAACTTAAAAATTAGCCTGTTGTC                       GTGGTGTGAGCCTGTGGTCCCAGCTACTCGGGAAACTGAGGCAAGAGGATTGCCTGAG                       CCCACGAGGTTGACGCTGAAGAAAGCCATGATCATGCCACTGCACTCCAGCTTGGCAA                       CAGAGCAAGGTTCTGTCTCAAAATAAATAAATACATAAATAAATAATAAAATAAAATA                       AAATAAATAAATAAAAAGCCCAGGCGTGATGGCTCACCCCTGTAATCCCAGCACTTTG                       GAAGGCCAAGGCACGCAGATCACCTCAGCTCAGGAGTACGAGACCACCCTGGGCAACA                       TGGGGTGAAACCTGTCTCTACTAAAATACAAAAAATTAGCCGGGTGTGGTGGCACGCG                       CCTGTAGTCCCAGCTACTTGGGAGGCTGAGACATGAGAATTGCTTGAGCCCAGGACGC                       GGAGGTTACAGTGAGGCGAAATTGCACCACTGCACTCCAGCTTGTCTCAAATAAATAA                       ATAAATAGAAAAAGGAAATTGCTAAGAGTAGATTTTAAGGGTTCTTACCACAAAAAAA                       ATGCTAAGTATGTGAGGTAATACATGTTAATTAGCTTGACTTACCATTCCACAATGTA                       CACATATTTCAAAACATCATGTTGTAGACAGTAAACATATACAATTTTTGTCAATTTA                       AAAAACAGAAAAGTTTAAAAAACAATGTCCTCAACCATCTTAGAAAACTGGATATGAA                       TGGTATCCTGCATAATGAAGTGCCTT                                       ORF Start: ATG at 157   ORF Stop: TGA at 400           SEQ ID NO:80   81 aa MW at 9245.7 kD                     NOV34a,   MSLPLNLKYFLSGLTGEPVMVKLKWGMEYKGYLVSVDGYMNMQLADTEFINEALPGHL               CG97378-01 Protein   GEVLIRCNNVLYIRDVEEEEMGK       Sequence                  
 
     [0434] 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 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:                  
 
     [0435] 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                                             Identities/                   NOV34a   Similarities               Residues/   for the       Geneseq   Protein/Organism/Length [Patent #,   Match   Matched   Expect       Identifier   Date]   Residues   Region   Value               AAU31044   Novel human secreted protein #1535 -   1 . . . 78   68/79 (86%)   3e−32             Homo sapiens , 124 aa. [WO200179449-   39 . . . 117   73/79 (92%)           A2, 25-OCT-2001]       ABB64039     Drosophila melanogaster  polypeptide SEQ   3 . . . 78   53/77 (68%)   2e−25           ID NO 18909 -  Drosophila melanogaster ,   1 . . . 77   69/77 (88%)           84 aa. [WO200171042-A2, 27-SEP-2001]       AAG33259     Zea mays  protein fragment SEQ ID NO:   2 . . . 77   50/77 (64%)   9e−24           40271 -  Zea mays  subsp. mays, 86 aa.   3 . . . 79   65/77 (83%)           [EP1033405-A2, 06-SEP-2000]       AAG12585     Zea mays  protein fragment SEQ ID NO:   2 . . . 77   50/77 (64%)   9e−24           11756 -  Zea mays  subsp. mays, 86 aa.   3 . . . 79   65/77 (83%)           [EP1033405-A2, 06-SEP-2000]       AAG33239     Zea mays  protein fragment SEQ ID NO:   2 . . . 77   49/77 (63%)   1e−23           40244 -  Zea mays  subsp. mays, 86 aa.   3 . . . 79   65/77 (83%)           [EP1033405-A2, 06-SEP-2000]                  
 
     [0436] 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                                             Identities/                   NOV34a   Similarities       Protein       Residues/   for the       Accession       Match   Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q15356   Small nuclear ribonucleoprotein F (snRNP-   1 . . . 78   68/79 (86%)   8e−32           F) (Sm protein F) (Sm-F) (SmF) -  Homo     1 . . . 79   73/79 (92%)             sapiens  (Human), 86 aa.       Q9V672   DEBB PROTEIN -  Drosophila     3 . . . 78   53/77 (68%)   4e−25             melanogaster  (Fruit fly), 84 aa.   1 . . . 77   69/77 (88%)       Q24297   Small nuclear ribonucleoprotein F (snRNP-   3 . . . 78   53/77 (68%)   4e−25           F) (Sm protein F) (Sm-F) (SmF)   5 . . . 81   69/77 (88%)           (Membrane-associated protein Deb-B) -             Drosophila melanogaster  (Fruit fly), 101 aa.       Q9SUM2   Probable small nuclear ribonucleoprotein F   2 . . . 78   50/78 (64%)   5e−23           (snRNP-F) (Sm protein F) (Sm-F) (SmF) -   3 . . . 80   65/78 (83%)             Arabidopsis thaliana  (Mouse-ear cress), 88           aa.       P34659   Probable small nuclear ribonucleoprotein F   4 . . . 77   46/75 (61%)   1e−18           (snRNP-F) (Sm protein F) (Sm-F) (SmF) -   6 . . . 80   58/75 (77%)           Caenorhabditis elegans, 85 aa.                  
 
     [0437] PFam analysis predicts that the NOV34a protein contains the domains shown in the Table 34E.  
               TABLE 34E                          Domain Analysis of NOV34a                                 NOV34a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               Sm   9 . . . 73   28/65 (43%)   1.1e−21               54/65 (83%)                  
 
     Example 35  
     [0438] 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   750 bp                     NOV35a,     GTGGCTGCTCGGGACCACCCGAACCCGCGGCC   ATG GCCCCGGCCGCCGCCAGCCCCCC               CG97966-01 DNA   GGAGGTGATCCGCGCGGCGCAGAAGGACGAGTACTACCGCGGTGGGCTGCGGAGCGCG               Sequence   GCGGGCGGCGCCCTGCACAGCCTGGCGGGTGCGGGGAAGTGGCTGGAGTGGAGGAAGG                   AGGTTGAGCTGCTCTCAGATGTGGCCTACTTTGGCCTCACCACACTTGCAGGCTACCA                   GACCCTGGGGGAGGAGTACGTCAGCATCATCCAGGTGGACCCATCGCGGATACATGTG                   CCCTCCTCGCTGCGCCGTGGCGTGCTGGTGACGCTGCATGCCGTCCTGCCCTACCTGC                   TGGACAAGGCCCTGCTCCCCCTGGAGCAGGACCTGCAGGCTGACCCCGACAGTGGGCG                   ACCCTTGCAGGGGAGCCTGGGGCCAGGTGGGCGTGGCTGCTCAGGGGCGCGGCGCTGG                   ATGCGTCACCACACGGCCACCCTGACTGAGCAGCAGAGGAGGGCGCTGCTGCGGGCGG                   TCTTCGTCCTCAGACAGGGCCTCGCCTGCCTCCAGCGCCTACATGTTGCCTGGTTTTA                   CATCCACCTGTTCTGCTGGGAGTGCATCACCGCCTGGTGCAGCAGCAAGGCGGAGTGT                   CCCCTCTGCCGGGAGAACTTCCCTCCCCAGAAGCTCATCTACCTTCGGCACTACCGC T                       GA   GCCGGCGCCCGGGTGGGCCTGGACACAGATGACCTCTACGGGAGTCTGAACG                                       ORF Start: ATG at 33   ORF Stop: ATG at 696           SEQ ID NO:82   221 aa MW at 24759.4 kD                     NOV35a,   MAPAAASPPEVIRAAQKDEYYRGGLRSAAGGALHSLAGAGKWLEWRKEVELLSDVAYF               CG97966-01 Protein   GLTTLAGYQTLGEEYVSIIQVDPSRIHVPSSLRRGVLVTLHAVLPYLLDKALLPLEQE               Sequence   LQADPDSGRPLQGSLGPGGRGCSGARRWMRHHTATLTEQQRRALLRAVFVLRQGLACL                   QRLHVAWFYIHLFCWECITAWCSSKAECPLCREKFPPQKLIYLRHYR                  
 
     [0439] Further analysis of the NOV35a protein yielded the following properties shown in Table 35B.  
               TABLE 35B                       Protein Sequence Properties NOV35a                                        PSort   0.4500 probability located in cytoplasm; 0.3774 probability       analysis:   located in microbody (peroxisome); 0.2542           probability located in lysosome (lumen);           0.1000 probability located in mitochondrial           matrix space       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0440] 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 35C.  
               TABLE 35C                          Geneseq Results for NOV35a                                         NOV35a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               AAB51471   Human secreted protein BLAST search   185 . . . 221   37/37 (100%)   3e−18           protein SEQ ID NO: 148 -  Homo sapiens ,   19 . . . 55   37/37 (100%)           55 aa. [WO200058495-A1, 05-OCT-2000]       AAB51470   Human secreted protein BLAST search   185 . . . 221   37/37 (100%)   3e−18           protein SEQ ID NO: 147 -  Homo sapiens ,   19 . . . 55   37/37 (100%)           55 aa. [WO200058495-A1, 05-OCT-2000]       AAB51469   Human secreted protein BLAST search   185 . . . 221   37/37 (100%)   3e−18           protein SEQ ID NO: 146 -  Homo sapiens ,   19 . . . 55   37/37 (100%)           55 aa. [WO200058495-A1, 05-OCT-2000]       AAB51468   Human secreted protein BLAST search   185 . . . 221   37/37 (100%)   3e−18           protein SEQ ID NO: 145 -  Homo sapiens ,   19 . . . 55   37/37 (100%)           55 aa. [WO200058495-A1, 05-OCT-2000]       AAG43363     Arabidopsis thaliana  protein fragment SEQ    6 . . . 108   39/103 (37%)    6e−13           ID NO: 54191 -  Arabidopsis thaliana , 381    29 . . . 131   59/103 (56%)            aa. [EP1033405-A2, 06-SEP-2000]                  
 
     [0441] 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 35D.  
               TABLE 35D                          Public BLASTP Results for NOV35a                                         NOV35a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9BW90   SIMILAR TO PEROXISOME    1 . . . 185   184/185 (99%)    e−103           BIOGENESIS FACTOR 10 -  Homo      1 . . . 185   184/185 (99%)             sapiens  (Human), 346 aa.       O60683   Peroxisome assembly protein 10    1 . . . 185   184/185 (99%)    e−103           (Peroxin-10) -  Homo sapiens  (Human),    1 . . . 185   184/185 (99%)           326 aa.       Q9M400   PEX10P -  Arabidopsis thaliana  (Mouse-    6 . . . 108    39/103 (37%)   1e−12           ear cress), 381 aa.   29 . . . 131    59/103 (56%)       Q9SYU4   ZINC-BINDING PEROXISOMAL    6 . . . 108    39/103 (37%)   1e−12           INTEGRAL MEMBRANE PROTEIN -   29 . . . 131    59/103 (56%)             Arabidopsis thaliana  (Mouse-ear cress),           381 aa.       Q94LL6   PUTATIVE ZINC-BINDING    6 . . . 108    38/103 (36%)   4e−11           PEROXISOMAL INTEGRAL   31 . . . 133    57/103 (54%)           MEMBRANE PROTEIN -  Oryza sativa             (Rice), 382 aa.                  
 
     [0442] PFam analysis predicts that the NOV35a protein contains the domains shown in the Table 35E.  
               TABLE 35E                          Domain Analysis of NOV35a                                 NOV35a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               zf-C3HC4   185 . . . 205    9/29 (31%)   0.011               16/29 (55%)                  
 
     Example 36  
     [0443] 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:83   1929 bp                     NOV36a,     CCTGTGTCCCCGGGTATGGGCTGGGGTCTGGC   ATG GGCCTCTGCAGCTGGCCACAGAC               CG99852-01 DNA   TGAGGGGCTCCAAACAGCACTGGGAACAGCCTCAGGGTATCTGTGGTTGGGGGCTGCA               Sequence   GACAGGGGTGGGGTCTTCTGCTTGGCCTTGACAGGTTGCAGCCACGTTGTCAGCCGCA                   TCTGCAATCTCATGGGGGCTTGGGGTCTTCCCGGCTCACGAGGTTATGGCAGAATTCA                   GCTCCTGGTGGCTGGGGACTGGGTCCCACCTCCCTGCTGGCTGTTGGCCCTTCCCAGC                   ATGGCGGTTGCTTCCCCTTCAGGGCCAGCAGGACTGGCCCGAATTTCTCCCTTTCTGG                   CGTTGAAACACCCTCTGGAGGGCTTCGTGATCGGGCCATGCCCGCCTAGGATGCTCTC                   CCTTCTGATGAGCTCAAGTCACCGGTTAGGGTCCTTAATCACATCGACAACACCCACC                   CCACCTGGCGAGTACAACGTGATCAGGGAAGGGATGCCCTGCTGCGGGAGGGGCCACG                   GGCGTGCACACCAGGTGGGAATCCGGTGGGAGAGGGCATCCCAGAGTCCTGCCTACTG                   GAGGGCTGGAGGGAGCAGAGTGGAGAGGGTGGGTTGGAGGGTGGTAGAAGGGCCAGGG                   GGCCAGCGGGGCGACTCAGCAGACCCTGTCTCAACCCGTAGGTCTGGAGTGGGACTGA                   CTGGCTCCAGACAGACCATGTTCTACACAGAGGTGACAGATGCCCAGCGTAGCGGTCC                   AGGTGGGGGCCTGGTGGAGGAGGGTGAGCTCATTGAGGTGGTGCACCTGCCCCTGGAA                   GGCGCCCAGGCCTTTGCAGACGACCCGGACATCCCCAAGACCCTCGGCGTCATCTTTG                   GTGTCTCATGGTTCCTCAGCCAGGTGGCCCCCAACCTGGATCTCCAG TGA   GACTCCAG                       G                                       ORF Start: ATG at 33   ORF Stop: TGA at 918           SEQ ID NO:84   295 aa MW at 31210.5 kD                     NOV36a,   MGLCSWPQTEGLQTALGTASGYLWLGAADRGGVFCLALTGCRQVVSRICNLMGAWGLP               CG99852-01 Protein   GSRGYGRIQLLVAGDWVPPPCWLLALPSMAVASPSGPACLARISPFLALKHPLEGFVI               Sequence   GPCPPRMLSLLMSSSHRLGSLITSTTPTPPGEYNVIREGNPCCGRGHGRAHQVGIRWE                   RASQSPAYWRAGGSRVERVGWRVVEGPGGQRGDSADPVSTRRSGVGLTGSRQTMFYTE                   VTDAQRSGPGGGLVEEGELIEVVHLPLEGAQAFADDPDIPKTLGVIFGVSWFLSQVAP                   NLDLQ                  
 
     [0444] Further analysis of the NOV36a protein yielded the following properties shown in Table 36B.  
               TABLE 36B                       Protein Sequence Properties NOV36a                                        PSort   0.5105 probability located in microbody (peroxisome); 0.5050       analysis:   probability located in cytoplasm; 0.3026           probability located in lysosome (lumen); 0.1000           probability located in mitochondrial matrix space       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0445] A search of the NOV36a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 36C.  
               TABLE 36C                          Geneseq Results for NOV36a                                             Identities/                   NOV36a   Similarities               Residues/   for the       Geneseq   Protein/Organism/Length [Patent #,   Match   Matched   Expect       Identifier   Date]   Residues   Region   Value               AAU22384   Human cardiovascular system antigen   216 . . . 295   80/80 (100%)   5e−40           polypeptide SEQ ID No: 1158 -  Homo      53 . . . 132   80/80 (100%)             sapiens , 132 aa. [WO200155321-A2, 02-AUG-2001]       ABB61994     Drosophila melanogaster  polypeptide SEQ   210 . . . 290   33/82 (40%)    2e−08           ID NO: 12774 -  Drosophila melanogaster ,   1268 . . . 1347   49/82 (59%)            1351 aa. [WO200171042-A2, 27-SEP-2001]       AAW98872     H. pylori  GHPO 1732 protein -   217 . . . 287   26/71 (36%)    0.002             Helicobacter pylori , 212 aa. [WO9843478-   140 . . . 208   36/71 (50%)            A1, 08-OCT-1998]       ABG18063   Novel human diagnostic protein #18054 -    25 . . . 103   31/82 (37%)    1.7              Homo sapiens , 717 aa. [WO200175067-   182 . . . 259   41/82 (49%)            A2, 11-OCT-2001]       ABG18063   Novel human diagnostic protein #18054 -    25 . . . 103   31/82 (37%)    1.7              Homo sapiens , 717 aa. [WO200175067-   182 . . . 259   41/82 (49%)            A2, 11-OCT-2001]                  
 
     [0446] In a BLAST search of public sequence datbases, the NOV36a protein was found to have homology to the proteins shown in the BLASTP data in Table 36D.  
               TABLE 36D                          Public BLASTP Results for NOV36a                                         NOV36a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9N034   UNNAMED PROTEIN PRODUCT -    1 . . . 295   258/295 (87%)    e−147             Macaca fascicularis  (Crab eating    1 . . . 295   265/295 (89%)           macaque) (Cynomolgus monkey), 295           aa.       O95848   HYPOTHETICAL 31.5 KDA PROTEIN -   212 . . . 295    81/84 (96%)   1e−39             Homo sapiens  (Human), 290 aa.   207 . . . 290    82/84 (97%)       Q9D142   1110030M18RIK PROTEIN -  Mus     164 . . . 295    77/132 (58%)   2e−31             musculus  (Mouse), 222 aa.   106 . . . 222    89/132 (67%)       Q9CSD2   1110030M18RIK PROTEIN -  Mus     164 . . . 295    76/132 (57%)   1e−30             musculus  (Mouse), 223 aa (fragment).   107 . . . 223    88/132 (66%)       Q9VB64   CG6001 PROTEIN -  Drosophila     210 . . . 290    33/82 (40%)   6e−08             melanogaster  (Fruit fly), 1351 aa.   1268 . . . 1347    49/82 (59%)                  
 
     [0447] PFam analysis predicts that the NOV36a protein contains the domains shown in the Table 36E.  
               TABLE 36E                       Domain Analysis of NOV36a                                                        Identities/           Pfam       Similarities   Expect       Domain   NOV36a Match Region   for the Matched Region   Value                  
 
     Example B  
     Identification of NOVX Clones  
     [0448] The novel NOVX target sequences identified in the present invention may have been subjected to the exon linking process to confirm the sequence. PCR primers are 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 is examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective is encountered, or, in the case of the reverse primer, until the stop codon is reached. Such primers are 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 are 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.  
     [0449] Usually the resulting amplicons are gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking is 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 are assembled with themselves, with other fragments in CuraGen Corporation&#39;s database and with public ESTs. Fragments and ESTs are included as components for an assembly when the extent of their identity with another component of the assembly is at least 95% over 50 bp. In addition, sequence traces are evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported herein.  
     Example C  
     Quantitative Expression Analysis of Clones in Various Cells and Tissues  
     [0450] The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoinflammatory diseases), Panel CNSD.01 (containing samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer&#39;s diseased brains).  
     [0451] 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.  
     [0452] First, the RNA samples were normalized to reference nucleic acids such as constitutively expressed genes (for example, β-actin and GAPDH). Normalized RNA (5 ul) was converted to cDNA and analyzed by RTQ-PCR using One Step RT-PCR Master Mix Reagents (Applied Biosystems; Catalog No. 4309169) and gene-specific primers according to the manufacturer&#39;s instructions.  
     [0453] 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&#39;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&#39;s instructions.  
     [0454] Probes and primers were designed for each assay according to Applied Biosystems Primer Express Software package (version I for Apple Computer&#39;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.  
     [0455] 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&#39;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.  
     [0456] 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&#39;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.  
     Panels 1, 1.1, 1.2, and 1.3D  
     [0457] 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.  
     [0458] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:  
     [0459] ca.=carcinoma,  
     [0460] *=established from metastasis,  
     [0461] met=metastasis,  
     [0462] s cell var=small cell variant,  
     [0463] non-s=non-sm=non-small,  
     [0464] squam=squamous,  
     [0465] pl. eff=pl effusion=pleural effusion,  
     [0466] glio=glioma,  
     [0467] astro=astrocytoma, and  
     [0468] neuro=neuroblastoma.  
     General_screening_panel_v1.4 and General_screening_panel_v1.5  
     [0469] The plates for Panels 1.4 and 1.5 include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panels 1.4 and 1.5 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 and 1.5 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 and 1.5 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.  
     Panels 2D, 2.2, 2.3 and 2.4  
     [0470] 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&#39;s Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI) or from Ardais or Clinomics). The tissues are derived from human malignancies and in cases where indicated many malignant tissues have “matched margins” obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted “NAT” in the results below. The tumor tissue and the “matched margins” are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues without malignancy (normal tissues) were also obtained from Ardais or Clinomics. This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, Calif.), Research Genetics, and Invitrogen.  
     HASS Panel v 1.0  
     [0471] The HASS panel v 1.0 plates are comprised of 93 cDNA samples and two controls.  
     [0472] 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.  
     Panel 3D  
     [0473] The plates of Panel 3D are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines, 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma of the tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D and 1.3D are of the most common cell lines used in the scientific literature.  
     Panels 4D, 4R, and 4.1D  
     [0474] 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&#39;s disease and ulcerative colitis was obtained from the National Disease Research Interchange (NDRI) (Philadelphia, Pa.).  
     [0475] 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.  
     [0476] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (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 −5 M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2×10 6  cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10 −5 M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.  
     [0477] Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer&#39;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 −5 M (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 −5 M (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.  
     [0478] 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&#39;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 −5 M (Gibco), and 10 mM Hepes (Gibco) and plated at 10 6 cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0.5 μg/ml anti-CD28 (Pharmingen) and 3ug/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 −5 M (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 −5 M (Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.  
     [0479] 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 10 6 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24,48 and 72 hours.  
     [0480] 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 10 5 -10 6 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), 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 −5 M (Gibco), 10mM 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.  
     [0481] 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 5×10 −5 cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×10 −5 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 −5 M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco). CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.  
     [0482] For these cell lines and blood cells, RNA was prepared by lysing approximately 10 7  cells/ml using Trizol (Gibco BRL). Briefly, {fraction (1/10)} volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 5 μl DTT, 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with 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.  
     AI_comprehensive panel_v1.0  
     [0483] The plates for Al_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.  
     [0484] 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.  
     [0485] 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.  
     [0486] 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&#39;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.  
     [0487] Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD was purchased from Clinomics. Emphysema patients ranged in age from 40-70 and all were smokers, this age range was chosen to focus on patients with cigarette-linked emphysema and to avoid those patients with alpha-1anti-trypsin deficiencies. Asthma patients ranged in age from 36-75, and excluded smokers to prevent those patients that could also have COPD. COPD patients ranged in age from 35-80 and included both smokers and non-smokers. Most patients were taking corticosteroids, and bronchodilators.  
     [0488] In the labels employed to identify tissues in the Al_comprehensive panel_v1.0 panel, the following abbreviations are used:  
     [0489] AI=Autoimmunity  
     [0490] Syn=Synovial  
     [0491] Normal=No apparent disease  
     [0492] Rep22/Rep20=individual patients  
     [0493] RA=Rheumatoid arthritis  
     [0494] Backus=From Backus Hospital  
     [0495] OA=Osteoarthritis  
     [0496] (SS) (BA) (MF)=Individual patients  
     [0497] Adj=Adjacent tissue  
     [0498] Match control=adjacent tissues  
     [0499] -M=Male  
     [0500] -F=Female  
     [0501] COPD=Chronic obstructive pulmonary disease  
     Panels 5D and 5I  
     [0502] 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.  
     [0503] In the Gestational Diabetes study subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (&lt;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:  
     [0504] Patient 2: Diabetic Hispanic, overweight, not on insulin  
     [0505] Patient 7-9: Nondiabetic Caucasian and obese (BMI&gt;30)  
     [0506] Patient 10: Diabetic Hispanic, overweight, on insulin  
     [0507] Patient 11: Nondiabetic African American and overweight  
     [0508] Patient 12: Diabetic Hispanic on insulin  
     [0509] 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:  
     [0510] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose  
     [0511] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated  
     [0512] Donor 2 and 3 AD: Adipose, Adipose Differentiated  
     [0513] 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.  
     [0514] Panel 5I contains all samples previously described with the addition of pancreatic islets from a 58 year old female patient obtained from the Diabetes Research Institute at the University of Miami School of Medicine. Islet tissue was processed to total RNA at an outside source and delivered to CuraGen for addition to panel 5I.  
     [0515] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:  
     [0516] GO Adipose=Greater Omentum Adipose  
     [0517] SK=Skeletal Muscle  
     [0518] UT=Uterus  
     [0519] PL=Placenta  
     [0520] AD=Adipose Differentiated  
     [0521] AM=Adipose Midway Differentiated  
     [0522] U=Undifferentiated Stem Cells  
     Panel CNSD.01  
     [0523] 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.  
     [0524] Disease diagnoses are taken from patient records. The panel contains two brains from each of the following diagnoses: Alzheimer&#39;s disease, Parkinson&#39;s disease, Huntington&#39;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&#39;s disease is characterized in part by neurodegeneration in the globus palladus, thus this region is impossible to obtain from confirmed Huntington&#39;s cases. Likewise Parkinson&#39;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.  
     [0525] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:  
     [0526] PSP=Progressive supranuclear palsy  
     [0527] Sub Nigra=Substantia nigra  
     [0528] Glob Palladus=Globus palladus  
     [0529] Temp Pole=Temporal pole  
     [0530] Cing Gyr=Cingulate gyrus  
     [0531] BA 4=Brodman Area 4  
     Panel CNS_Neurodegeneration_V1.0  
     [0532] The plates for Panel CNS_Neurodegeneration_V1.0 include two control wells and 47 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center (McLean Hospital) and the Human Brain and Spinal Fluid Resource Center (VA Greater Los Angeles Healthcare System). Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.  
     [0533] Disease diagnoses are taken from patient records. The panel contains six brains from Alzheimer&#39;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&#39;s like pathology (Controls) and controls with no dementia but evidence of severe Alzheimer&#39;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.  
     [0534] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:  
     [0535] AD=Alzheimer&#39;s disease brain; patient was demented and showed AD-like pathology upon autopsy  
     [0536] Control=Control brains; patient not demented, showing no neuropathology  
     [0537] Control (Path)=Control brains; patient not demented but showing sever AD-like pathology  
     [0538] SupTemporal Ctx=Superior Temporal Cortex  
     [0539] Inf Temporal Ctx=Inferior Temporal Cortex  
     A. NOV5a (CG94620-01): Progesterone Receptor-associated P48 Protein  
     [0540] Expression of gene CG94620-01 was assessed using the primer-probe set Ag3930, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB, and AC.  
               TABLE AA                          Probe Name Ag3930                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-gtgcaggatcccaaagttagt-3′   21   974   85               Probe   TET-5′-tggctcaaaacccagcaaatatgtca-3′-TAMRA   26   1011   86               Reverse   5′-ctttgggttgccctggtat-3′   19   1039   87                  
 
     [0541]               TABLE AB                          General_screening_panel_v1.4                                 Rel. Exp.       Rel. Exp.           (%) Ag3930,       (%) Ag3930,           Run       Run       Tissue Name   219478617   Tissue Name   219478617                                     Adipose   6.1   Renal ca. TK-10   9.3       Melanoma*   24.5   Bladder   37.1       Hs688(A).T       Melanoma*   19.9   Gastric ca. (liver met.)   43.8       Hs688(B).T       NCI-N87       Melanoma* M14   10.6   Gastric ca. KATO III   8.1       Melanoma*   0.5   Colon ca. SW-948   6.3       LOXIMVI       Melanoma* SK-   8.9   Colon ca. SW480   29.3       MEL-5       Squamous cell   0.0   Colon ca.* (SW480   12.3       carcinoma SCC-4       met) SW620       Testis Pool   20.3   Colon ca. HT29   12.0       Prostate ca.* (bone   33.2   Colon ca. HCT-116   48.6       met) PC-3       Prostate Pool   6.2   Colon ca. CaCo-2   43.2       Placenta   5.3   Colon cancer tissue   20.0       Uterus Pool   24.5   Colon ca. SW1116   0.5       Ovarian ca.   6.7   Colon ca. Colo-205   0.7       OVCAR-3       Ovarian ca. SK-   100.0   Colon ca. SW-48   0.4       OV-3       Ovarian ca.   3.0   Colon Pool   42.6       OVCAR-4       Ovarian ca.   1.3   Small Intestine   64.2       OVCAR-5       Pool       Ovarian ca.   16.3   Stomach Pool   30.6       IGROV-1       Ovarian ca.   6.6   Bone Marrow Pool   21.3       OVCAR-8       Ovary   11.3   Fetal Heart   14.0       Breast ca. MCF-7   4.6   Heart Pool   15.3       Breast ca. MDA-   50.3   Lymph Node Pool   58.6       MB-231       Breast ca. BT 549   4.5   Fetal Skeletal Muscle   8.2       Breast ca. T47D   9.8   Skeletal Muscle Pool   2.4       Breast ca. MDA-N   0.5   Spleen Pool   29.3       Breast Pool   55.1   Thymus Pool   39.5       Trachea   37.4   CNS cancer (glio/   1.0               astro) U87-MG       Lung   18.2   CNS cancer (glio/   2.0               astro) U-118-MG       Fetal Lung   40.6   CNS cancer   15.1               (neuro;met) SK-N-AS       Lung ca. NCI-N417   1.5   CNS cancer (astro)   3.0               SF-539       Lung ca. LX-1   23.0   CNS cancer (astro)   17.3               SNB-75       Lung ca. NCI-H146   0.9   CNS cancer (glio)   3.3               SNB-19       Lung ca. SHP-77   10.0   CNS cancer (glio) SF-   61.6               295       Lung ca. A549   6.7   Brain (Amygdala)   8.7               Pool       Lung ca. NCI-H526   3.2   Brain (cerebellum)   12.1       Lung ca. NCI-H23   25.0   Brain (fetal)   25.5       Lung ca. NCI-H460   40.1   Brain (Hippocampus)   12.1               Pool       Lung ca. HOP-62   18.3   Cerebral Cortex Pool   14.7       Lung ca. NCI-H522   14.3   Brain (Substantia   9.7               nigra) Pool       Liver   1.2   Brain (Thalamus) Pool   17.2       Fetal Liver   4.6   Brain (whole)   4.9       Liver ca. HepG2   12.1   Spinal Cord Pool   20.6       Kidney Pool   76.3   Adrenal Gland   31.2       Fetal Kidney   18.2   Pituitary gland Pool   8.5       Renal ca. 786-0   8.1   Salivary Gland   3.2       Renal ca. A498   0.0   Thyroid (female)   1.8       Renal ca. ACHN   6.5   Pancreatic ca.   7.0               CAPAN2       Renal ca. UO-31   4.5   Pancreas Pool   43.8                    
     [0542]               TABLE AC                          Panel 4.1D                                 Rel. Exp.       Rel. Exp.           (%) Ag3930,       (%) Ag3930,           Run       Run       Tissue Name   170701768   Tissue Name   170701768                                     Secondary Th1 act   12.2   HUVEC IL-1beta   3.7       Secondary Th2 act   4.5   HUVEC IFN gamma   4.3       Secondary Tr1 act   10.9   HUVEC TNF alpha +   1.1               IFN gamma       Secondary Th1 rest   4.6   HUVEC TNF alpha +   1.1               IL4       Secondary Th2 rest   7.3   HUVEC IL-11   4.5       Secondary Tr1 rest   7.7   Lung Microvascular   9.8               EC none       Primary Th1 act   8.5   Lung Microvascular   4.3               EC TNFalpha +               IL-1beta       Primary Th2 act   19.1   Microvasucular   3.7               Dermal EC none       Primary Tr1 act   6.4   Microsvasular   1.5               Dermal EC               TNFalpha + IL-1beta       Primary Th1 rest   7.9   Bronchial epithelium   9.4               TNFalpha + IL1beta       Primary Th2 rest   7.0   Small airway   1.2               epithelium none       Primary Tr1 rest   10.8   Small airway   6.8               epithelium               TNFalpha + IL-1beta       CD45RA CD4   9.6   Coronery artery SMC   4.5       lymphocyte act       rest       CD45RO CD4   14.7   Coronery artery SMC   1.3       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   14.4   Astrocytes rest   3.2       Secondary CD8   8.9   Astrocytes INFalpha +   5.1       lymphocyte rest       IL-1beta       Secondary CD8   4.2   KU-812 (Basophil)   15.3       lymphocyte act       rest       CD4 lymphocyte   7.8   KU-812 (Basophil)   11.6       none       PMA/ionomycin       2ry Th1/Th2/   13.6   CCD1106 (Keratino-   0.5       Tr1_anti-CD95       cytes) none       CH11       LAK cells rest   10.8   CCD1106 (Keratino-   4.1               cytes) TNFalpha +               IL-1beta       LAK cells IL-2   13.2   Liver cirrhosis   3.7       LAK cells IL-2 +   6.7   NCI-H292 none   4.7       IL-12       LAK cells IL-2 +   7.9   NCI-H292 IL-4   9.7       IFN gamma       LAK cells IL-2 +   19.5   NCI-H292 IL-9   3.1       IL-18       LAK cells   8.4   NCI-H292 IL-13   4.8       PMA/ionomycin       NK Cells IL-2 rest   21.0   NCI-H292 IFN gamma   4.9       Two Way MLR 3   17.4   HPAEC none   2.2       day       Two Way MLR 5   8.8   HPAEC TNF alpha +   7.2       day       IL-1 beta       Two Way MLR 7   9.7   Lung fibroblast none   3.7       day       PBMC rest   2.4   Lung fibroblast TNF   2.0               alpha + IL-1 beta       PBMC PWM   7.1   Lung fibroblast IL-4   0.6       PBMC PHA-L   7.5   Lung fibroblast IL-9   2.4       Ramos (B cell) none   2.2   Lung fibroblast IL-13   1.5       Ramos (B cell)   1.2   Lung fibroblast IFN   7.3       ionomycin       gamma       B lymphocytes   7.4   Dermal fibroblast   8.4       PWM       CCD1070 rest       B lymphocytes   20.2   Dermal fibroblast   20.3       CD40L and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   10.9   Dermal fibroblast   2.7               CCD1070 IL-1 beta       EOL-1 dbcAMP   16.4   Dermal fibroblast IFN   0.7       PMA/ionomycin       gamma       Dendritic cells none   12.8   Dermal fibroblast IL-4   7.2       Dendritic cells LPS   7.3   Dermal Fibroblasts   1.3               rest       Dendritic cells anti-   3.8   Neutrophils TNFa +   0.8       CD40       LPS       Monocytes rest   12.6   Neutrophils rest   12.6       Monocytes LPS   10.6   Colon   1.7       Macrophages rest   11.0   Lung   9.3       Macrophages LPS   2.0   Thymus   33.7       HUVEC none   1.6   Kidney   100.0       HUVEC starved   4.7                    
     [0543] General_screening_panel_v1.4 Summary: Ag3930 Highest expression of the CG94620-01 gene is seen in an ovarian cancer cell line (CT=30.8), with prominent levels of expression also seen in a brain cancer cell lines when compared to expression in the normal tissue. Thus, expression of this gene could be used as a marker for these types of cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of brain and ovarian cancers.  
     [0544] Among tissues with metabolic function, this gene is expressed at low but significant levels in pituitary, adipose, adrenal gland, pancreas, fetal skeletal muscle and adult and fetal heart. 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.  
     [0545] 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 neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0546] Panel 4.1D Summary: Ag3930 Highest expression of the CG94620-01 gene is seen in the kidney (CT=30.7), with low but significant levels of expression seen in many of the samples on this panel. The higher levels of expression of this gene suggest that expression of this gene could be used to differentiate this sample from other samples on this panel and as a marker of kidney tissue. Furthermore, antibody or small molecule therapies designed with the protein encoded by this gene could modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.  
     B. NOV6a (CG94882-01): Rho GAP  
     [0547] Expression of gene CG94882-01 was assessed using the primer-probe set Ag3958, described in Table BA. Results of the RTQ-PCR runs are shown in Tables BB, BC and BD.  
               TABLE BA                          Probe Name Ag3958                                             Start   SEQ ID       Primers   Sequences   Length   Postion   No                                         Forward   5′-cttcttcctcttcgacaacctt-3′   22   531   88               Probe   TET-5′-ctcgtctactgcaagcggaaatccag-3′-TAMRA   26   553   89               Reverse   5′-gtcctcttggtggacttcttg-3′   21   591   90                  
 
     [0548]               TABLE BB                          CNS_neurodegeneration_v1.0                                 Rel. Exp.       Rel. Exp.           (%) Ag3958,       (%) Ag3958,           Run       Run       Tissue Name   249265943   Tissue Name   249265943                                     AD 1 Hippo   35.8   Control (Path) 3   11.5               Temporal Ctx       AD 2 Hippo   37.6   Control (Path) 4   25.5               Temporal Ctx       AD 3 Hippo   21.8   AD 1 Occipital Ctx   32.3       AD 4 Hippo   21.2   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   55.5   AD 3 Occipital Ctx   24.0       AD 6 Hippo   99.3   AD 4 Occipital Ctx   37.9       Control 2 Hippo   37.1   AD 5 Occipital Ctx   38.7       Control 4 Hippo   34.6   AD 6 Occipital Ctx   36.9       Control (Path) 3   15.2   Control 1 Occipital   11.2       Hippo       Ctx       AD 1 Temporal Ctx   49.0   Control 2 Occipital   46.7               Ctx       AD 2 Temporal Ctx   35.8   Control 3 Occipital   23.0               Ctx       AD 3 Temporal Ctx   25.0   Control 4 Occipital   23.0               Ctx       AD 4 Temporal Ctx   40.1   Control (Path) 1   71.2               Occipital Ctx       AD 5 Inf Temporal   90.8   Control (Path) 2   13.4       Ctx       Occipital Ctx       AD 5 SupTemporal   45.1   Control (Path) 3   15.4       Ctx       Occipital Ctx       AD 6 Inf Temporal   100.0   Control (Path) 4   16.6       Ctx       Occipital Ctx       AD 6 Sup Temporal   84.7   Control 1 Parietal   22.5       Ctx       Ctx       Control 1 Temporal   15.2   Control 2 Parietal   61.6       Ctx       Ctx       Control 2 Temporal   43.2   Control 3 Parietal   21.5       Ctx       Ctx       Control 3 Temporal   21.5   Control (Path) 1   64.2       Ctx       Parietal Ctx       Control 4 Temporal   22.2   Control (Path) 2   27.5       Ctx       Parietal Ctx       Control (Path) 1   39.0   Control (Path) 3   10.9       Temporal Ctx       Parietal Ctx       Control (Path) 2   37.9   Control (Path) 4   31.2       Temporal Ctx       Parietal Ctx                    
     [0549]               TABLE BC                          General_screening_panel_v1.4                                 Rel. Exp.       Rel. Exp.           (%) Ag3958,       (%) Ag3958,           Run       Run       Tissue Name   219922886   Tissue Name   219922886                                     Adipose   9.2   Renal ca.TK-10   0.6       Melanoma*   2.1   Bladder   12.5       Hs688(A).T       Melanoma*   1.2   Gastric ca. (liver met.)   0.0       Hs688(B).T       NCI-N87       Melanoma* M14   6.5   Gastric ca. KATO III   0.1       Melanoma*   7.6   Colon ca. SW-948   0.0       LOXIMVI       Melanoma* SK-   11.5   Colon ca. SW480   3.2       MEL-5       Squamous cell   0.8   Colon ca.* (SW480   3.8       carcinoma SCC-4       met) SW620       Testis Pool   3.7   Colon ca. HT29   0.0       Prostate ca.* (bone   10.7   Colon ca. HCT-116   3.8       met) PC-3       Prostate Pool   2.5   Colon ca. CaCo-2   1.4       Placenta   6.0   Colon cancer tissue   8.0       Uterus Pool   1.3   Colon ca. SW1116   0.0       Ovarian ca.   3.8   Colon ca. Colo-205   0.0       OVCAR-3       Ovarian ca. SK-   18.6   Colon ca. SW-48   0.0       OV-3       Ovarian ca.   5.6   Colon Pool   5.2       OVCAR-4       Ovarian ca.   30.8   Small Intestine Pool   2.8       OVCAR-5       Ovarian ca.   2.5   Stomach Pool   3.6       IGROV-1       Ovarian ca.   2.4   Bone Marrow Pool   2.0       OVCAR-8       Ovary   2.3   Fetal Heart   6.3       Breast ca. MCF-7   84.1   Heart Pool   2.0       Breast ca. MDA-   0.0   Lymph Node Pool   4.0       MB-231       Breast ca. BT 549   0.0   Fetal Skeletal Muscle   3.5       Breast ca. T47D   100.0   Skeletal Muscle Pool   3.6       Breast ca. MDA-N   8.7   Spleen Pool   20.6       Breast Pool   4.6   Thymus Pool   8.5       Trachea   6.5   CNS cancer (glio/   69.7               astro) U87-MG       Lung   0.5   CNS cancer (glio/   22.8               astro) U-118-MG       Fetal Lung   31.6   CNS cancer   2.3               (neuro;met) SK-N-AS       Lung ca. NCI-N417   6.4   CNS cancer (astro)   1.3               SF-539       Lung ca. LX-1   1.5   CNS cancer (astro)   4.4               SNB-75       Lung ca. NCI-H146   14.6   CNS cancer (glio)   2.5               SNB-19       Lung ca. SHP-77   3.8   CNS cancer (glio) SF-   5.7               295       Lung ca. A549   6.8   Brain (Amygdala)   18.9               Pool       Lung ca. NCI-H526   7.4   Brain (cerebellum)   43.8       Lung ca. NCI-H23   2.1   Brain (fetal)   17.6       Lung ca. NCI-   0.1   Brain (Hippocampus)   21.9       H460       Pool       Lung ca. HOP-62   0.0   Cerebral Cortex Pool   25.7       Lung ca. NCI-H522   1.9   Brain (Substantia   19.1               nigra) Pool       Liver   1.7   Brain (Thalamus) Pool   29.9       Fetal Liver   9.5   Brain (whole)   25.5       Liver ca. HepG2   0.0   Spinal Cord Pool   30.1       Kidney Pool   5.6   Adrenal Gland   11.3       Fetal Kidney   4.2   Pituitary gland Pool   2.7       Renal ca. 786-0   0.0   Salivary Gland   1.8       Renal ca. A498   2.0   Thyroid (female)   2.6       Renal ca. ACHN   6.4   Pancreatic ca.   0.1               CAPAN2       Renal ca. UO-31   2.6   Pancreas Pool   5.3                    
     [0550]               TABLE BD                          general oncology screening panel_v_2.4                                 Rel. Exp.       Rel. Exp.           (%) Ag3958,       (%) Ag3958,           Run       Run       Tissue Name   268143866   Tissue Name   268143866                                     Colon cancer 1   17.2   Bladder cancer NAT 2   0.5       Colon NAT 1   18.0   Bladder cancer NAT 3   0.7       Colon cancer 2   12.3   Bladder cancer NAT 4   1.3       Colon cancer   5.3   Adenocarcinoma of the   29.9       NAT 2       prostate 1       Colon cancer 3   15.5   Adenocarcinoma of the   4.3               prostate 2       Colon cancer   6.8   Adenocarcinoma of the   6.6       NAT 3       prostate 3       Colon malignant   34.2   Adenocarcinoma of the   10.0       cancer 4       prostate 4       Colon normal   3.5   Prostate cancer NAT 5   5.8       adjacent tissue 4       Lung cancer 1   33.0   Adenocarcinoma of the   1.8               prostate 6       Lung NAT 1   7.3   Adenocarcinoma of the   3.4               prostate 7       Lung cancer 2   67.4   Adenocarcinoma of the   1.0               prostate 8       Lung NAT 2   14.0   Adenocarcinoma of the   14.6               prostate 9       Squamous cell   31.6   Prostate cancer NAT 10   0.8       carcinoma 3       Lung NAT 3   6.3   Kidney cancer 1   72.7       metastatic   6.0   KidneyNAT 1   25.0       melanoma 1       Melanoma 2   2.4   Kidney cancer 2   100.0       Melanoma 3   2.7   Kidney NAT 2   15.9       metastatic   20.0   Kidney cancer 3   32.3       melanoma 4       metastatic   33.0   Kidney NAT 3   7.2       melanoma 5       Bladder cancer 1   1.8   Kidney cancer 4   27.5       Bladder cancer   0.0   Kidney NAT 4   7.2       NAT 1       Bladder cancer 2   5.4                    
     [0551] CNS_neurodegeneration_v1.0 Summary: Ag3958 This panel confirms the expression of the CG94882-01 gene in the brain in an independent group of individuals. This gene is found to be upregulated in the temporal cortex of Alzheimer&#39;s disease patients. Therefore, therapeutic modulation of the expression or function of this gene or gene product may decrease neuronal death and be of use in the treatment of this disease.  
     [0552] General_screening_panel_v1.4 Summary: Ag3958 Highest expression of the CG94882-01 gene is seen in a breast cancer cell line (CT=24.6). Significant levels of expression are also seen in a second breast cancer cell line. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker for breast cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of breast cancer.  
     [0553] Among tissues with metabolic function, this gene is expressed at high to moderate levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0554] This gene is also expressed at high levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0555] general oncology screening panel_v — 2.4 Summary: Ag3958 Highest expression of the CG94882-01 gene is seen in kidney cancer (CT=26.5). Significant levels of expression are also seen in kidney cancer, lung cancer and prostate cancer when compared to expression in corresponding normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene could be effective in the treatment of lung, kidney and prostate cancers.  
     C. NOV7a (CG94915-01): DELTEX3  
     [0556] Expression of gene CG94915-01 was assessed using the primer-probe sets Ag1983 and Ag3962, described in Tables CA and CB. Results of the RTQ-PCR runs are shown in Tables CC, CD, CE, CF, CG, CH and CI.  
               TABLE CA                          Probe Name Ag1983                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-cagcttccaaagagtaaaagca-3′   22   4493   91               Probe   TET-5′-tctgcaatctcccacaccatgaact-3′-TAMRA   26   4454   92               Reverse   5′-gagattgcactgtgtgtgacat-3′   22   4429   92                  
 
     [0557]               TABLE CB                          Probe Name Ag3962                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-caggaaagagataccctggaat-3′   22   818   94               Probe   TET-5′-cagcgaactgcatacttgcctgataa-3′-TAMRA   26   841   95               Reverse   5′-cagtttcaaaaccttccttcct-3′   22   873   96                    
     [0558]               TABLE CC                          CNS_neurodegeneration_v1.0                                 Rel. Exp.       Rel. Exp.           (%) Ag3962,       (%) Ag3962,           Run       Run       Tissue Name   212343354   Tissue Name   212343354                                     AD 1 Hippo   23.8   Control (Path) 3   14.5               Temporal Ctx       AD 2 Hippo   30.1   Control (Path) 4   29.3               Temporal Ctx       AD 3 Hippo   13.1   AD 1 Occipital Ctx   15.6       AD 4 Hippo   10.0   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   52.1   AD 3 Occipital Ctx   14.6       AD 6 Hippo   100.0   AD 4 Occipital Ctx   12.9       Control 2 Hippo   25.5   AD 5 Occipital Ctx   29.3       Control 4 Hippo   25.2   AD 6 Occipital Ctx   22.1       Control (Path) 3   19.3   Control 1 Occipital   21.2       Hippo       Ctx       AD 1 Temporal Ctx   26.1   Control 2 Occipital   28.1               Ctx       AD 2 Temporal Ctx   24.5   Control 3 Occipital   15.7               Ctx       AD 3 Temporal Ctx   8.1   Control 4 Occipital   15.5               Ctx       AD 4 Temporal Ctx   17.9   Control (Path) 1   39.5               Occipital Ctx       AD 5 Inf Temporal   54.7   Control (Path) 2   7.6       Ctx       Occipital Ctx       AD 5 SupTemporal   90.8   Control (Path) 3   14.0       Ctx       Occipital Ctx       AD 6 Inf Temporal   97.9   Control (Path) 4   26.6       Ctx       Occipital Ctx       AD 6 Sup Temporal   96.6   Control 1 Parietal   20.0       Ctx       Ctx       Control 1 Temporal   13.7   Control 2 Parietal   55.9       Ctx       Ctx       Control 2 Temporal   26.6   Control 3 Parietal   9.7       Ctx       Ctx       Control 3 Temporal   14.2   Control (Path) 1   29.5       Ctx       Parietal Ctx       Control 4 Temporal   11.0   Control (Path) 2   27.2       Ctx       Parietal Ctx       Control (Path) 1   33.9   Control (Path) 3   17.1       Temporal Ctx       Parietal Ctx       Control (Path) 2   35.8   Control (Path) 4   31.0       Temporal Ctx       Parietal Ctx                    
     [0559]               TABLE CD                          General_screening_panel_v1.4                                 Rel. Exp.       Rel. Exp.           (%) Ag3962,       (%) Ag3962,           Run       Run       Tissue Name   217333830   Tissue Name   217333830                                     Adipose   6.0   Renal ca. TK-10   11.3       Melanoma*   5.4   Bladder   26.8       Hs688(A).T       Melanoma*   3.8   Gastric ca. (liver met.)   100.0       Hs688(B).T       NCI-N87       Melanoma* M14   15.1   Gastric ca. KATO III   36.3       Melanoma*   3.6   Colon ca. SW-948   2.8       LOXIMVI       Melanoma* SK-   11.8   Colon ca. SW480   9.9       MEL-5       Squamous cell   13.4   Colon ca.* (SW480   5.4       carcinoma SCC-4       met) SW620       Testis Pool   1.4   Colon ca. HT29   6.5       Prostate ca.* (bone   7.1   Colon ca. HCT-116   3.8       met) PC-3       Prostate Pool   3.0   Colon ca. CaCo-2   5.0       Placenta   1.6   Colon cancer tissue   9.2       Uterus Pool   1.7   Colon ca. SW1116   1.1       Ovarian ca.   37.4   Colon ca Colo-205   5.6       OVCAR-3       Ovarian ca. SK-   12.0   Colon ca. SW-48   7.1       OV-3       Ovarian ca.   8.4   Colon Pool   5.6       OVCAR-4       Ovarian ca.   15.1   Small Intestine Pool   7.2       OVCAR-5       Ovarian ca.   6.2   Stomach Pool   4.3       IGROV-1       Ovarian ca.   6.5   Bone Marrow Pool   3.6       OVCAR-8       Ovary   6.4   Fetal Heart   1.7       Breast ca. MCF-7   6.0   Heart Pool   2.8       Breast ca. MDA-   9.3   Lymph Node Pool   6.3       MB-231       Breast ca. BT 549   54.0   Fetal Skeletal Muscle   2.1       Breast ca. T47D   24.8   Skeletal Muscle Pool   5.5       Breast ca. MDA-N   22.7   Spleen Pool   10.2       Breast Pool   5.9   Thymus Pool   6.4       Trachea   6.4   CNS cancer (glio/   7.2               astro) U87-MG       Lung   2.9   CNS cancer (glio/   18.3               astro) U-118-MG       Fetal Lung   12.7   CNS cancer   11.7               (neuro;met) SK-N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro)   12.2               SF-539       Lung ca. LX-1   6.5   CNS cancer (astro)   24.1               SNB-75       Lung ca. NCI-H146   1.2   CNS cancer (glio)   5.0               SNB-19       Lung ca. SHP-77   3.4   CNS cancer (glio) SF-   21.6               295       Lung ca. A549   4.7   Brain (Amygdala)   0.8               Pool       Lung ca. NCI-H526   1.3   Brain (cerebellum)   0.7       Lung ca. NCI-H23   5.3   Brain (fetal)   0.7       Lung ca. NCI-H460   3.1   Brain (Hippocampus)   1.1               Pool       Lung ca. HOP-62   5.0   Cerebral Cortex Pool   0.7       Lung ca. NCI-H522   0.6   Brain (Substantia   0.6               nigra) Pool       Liver   1.3   Brain (Thalamus) Pool   1.2       Fetal Liver   11.7   Brain (whole)   1.5       Liver ca. HepG2   1.8   Spinal Cord Pool   1.7       Kidney Pool   10.8   Adrenal Gland   3.6       Fetal Kidney   3.3   Pituitary gland Pool   0.8       Renal ca. 786-0   13.5   Salivary Gland   1.4       Renal ca. A498   4.8   Thyroid (female)   3.0       Renal ca. ACHN   6.0   Pancreatic ca.   13.0               CAPAN2       Renal ca. UO-31   14.0   Pancreas Pool   8.9                    
     [0560]               TABLE CE                          Panel 1.3D                                 Rel. Exp.       Rel. Exp.           (%) Ag1983,       (%) Ag1983,           Run       Run       Tissue Name   147734681   Tissue Name   147734681                                     Liver   5.4   Kidney (fetal)   3.8       adenocarcinoma       Pancreas   2.1   Renal ca. 786-0   2.8       Pancreatic ca.   0.8   Renal ca. A498   16.4       CAPAN 2       Adrenal gland   5.5   Renal ca. RXF 393   2.0       Thyroid   5.8   Renal ca. ACHN   2.1       Salivary gland   4.9   Renal ca. UO-31   2.6       Pituitary gland   5.1   Renal ca. TK-10   2.4       Brain (fetal)   0.3   Liver   10.4       Brain (whole)   0.9   Liver (fetal)   12.9       Brain (amygdala)   2.3   Liver ca.   2.1               (hepatoblast) HepG2       Brain (cerebellum)   0.2   Lung   12.2       Brain   3.0   Lung (fetal)   15.5       (hippocampus)       Brain (substantia   3.6   Lung ca. (small cell)   1.2       nigra)       LX-7       Brain (thalamus)   2.6   Lung ca. (small cell)   0.7               NCI-H69       Cerebral Cortex   0.9   Lung ca. (s.cell var.)   1.7               SHP-77       Spinal cord   4.1   Lung ca. (large   1.2               cell)NCI-H460       glio/astro U87-MG   3.7   Lung ca. (non-sm.   1.2               cell) A549       glio/astro   9.8   Lung ca. (non-s.cell)   0.0       U-118-MG       NCI-H23       astrocytoma   0.6   Lung ca. (non-s.cell)   2.4       SW1783       HOP-62       neuro*; met   10.0   Lung ca. (non-s.cl)   0.2       SK-N-AS       NCI-H522       astrocytoma SF-539   13.8   Lung ca. (squam.)   2.3               SW 900       astrocytoma   21.2   Lung ca. (squam.)   0.0       SNB-75       NCI-H596       glioma SNB-19   4.5   Mammary gland   0.1       glioma U251   3.4   Breast ca.* (pl.ef)   1.2               MCF-7       glioma SF-295   5.3   Breast ca.* (pl.ef)   11.5               MDA-MB-231       Heart (fetal)   1.9   Breast ca.* (pl.ef)   6.3               T47D       Heart   2.0   Breast ca. BT-549   16.7       Skeletal muscle   3.8   Breast ca. MDA-N   16.2       (fetal)       Skeletal muscle   1.4   Ovary   0.6       Bone marrow   8.5   Ovarian ca.   18.6               OVCAR-3       Thymus   5.6   Ovarian ca.   0.5               OVCAR-4       Spleen   19.5   Ovarian ca.   5.0               OVCAR-5       Lymph node   12.9   Ovarian ca.   2.8               OVCAR-8       Colorectal   1.2   Ovarian ca. IGROV-   0.9               1       Stomach   15.6   Ovarian ca.*   2.9               (ascites) SK-OV-3       Small intestine   14.5   Uterus   6.8       Colon ca. SW480   4.0   Placenta   15.1       Colon ca.*   1.1   Prostate   9.6       SW620(SW480       met)       Colon ca. HT29   2.7   Prostate ca.* (bone   1.3               met)PC-3       Colon ca. HCT-116   0.9   Testis   1.5       Colon ca. CaCo-2   4.5   Melanoma   3.3               Hs688(A).T       Colon ca.   11.2   Melanoma* (met)   8.2       tissue (ODO3866)       Hs688(B).T       Colon ca. HCC-   19.9   Melanoma UACC-   0.3       2998       62       Gastric ca.* (liver   100.0   Melanoma M14   1.7       met) NCI-N87       Bladder   3.8   Melanoma LOX   0.2               IMVI       Trachea   17.8   Melanoma* (met)   0.0               SK-MEL-5       Kidney   1.9   Adipose   3.5                    
     [0561]               TABLE CF                          Panel 2D                                 Rel. Exp.       Rel. Exp.           (%) Ag1983,       (%) Ag1983,           Run       Run       Tissue Name   147734710   Tissue Name   1147734710                                     Normal Colon   25.7   Kidney Margin   1.7               8120608       CC Well to Mod Diff   9.4   Kidney Cancer   3.8       (ODO3866)       8120613       CC Margin   11.3   Kidney Margin   1.1       (ODO3866)       8120614       CC Gr.2 rectosigmoid   4.1   Kidney Cancer   9.8       (ODO3868)       9010320       CC Margin   4.0   Kidney Margin   5.4       (ODO3868)       9010321       CC Mod Duff   14.6   Normal Uterus   4.3       (ODO3920)       CC Margin   11.3   Uterus Cancer   14.4       (ODO3920)       064011       CC Gr.2 ascend colon   28.3   Normal Thyroid   7.4       (ODO3921)       CC Margin   8.7   Thyroid Cancer   19.2       (ODO3921)       064010       CC from Partial   32.8   Thyroid Cancer   12.8       Hepatectomy       A302152       (ODO4309) Mets       Liver Margin   27.0   Thyroid Margin   20.0       (ODO4309)       A302153       Colon mets to lung   9.0   Normal Breast   15.0       (OD04451-01)       Lung Margin   14.8   Breast Cancer   36.1       (OD04451-02)       (OD04566)       Normal Prostate   16.8   Breast Cancer   25.0       6546-1       (OD04590-01)       Prostate Cancer   21.8   Breast Cancer Mets   26.4       (OD04410)       (OD04590-03)       Prostate Margin   26.8   Breast Cancer   40.9       (OD04410)       Metastasis               (OD04655-05)       Prostate Cancer   16.3   Breast Cancer   27.0       (OD04720-01)       064006       Prostate Margin   34.4   Breast Cancer 1024   19.8       (OD04720-02)       Normal Lung 061010   30.8   Breast Cancer   22.2               9100266       Lung Met to Muscle   18.9   Breast Margin   4.9       (ODO4286)       9100265       Muscle Margin   10.5   Breast Cancer   18.8       (ODO4286)       A209073       Lung Malignant   20.2   Breast Margin   10.8       Cancer (OD03126)       A209073       Lung Margin   43.2   Normal Liver   13.9~       (OD03126)       Lung Cancer   43.2   Liver Cancer   7.2       (OD04404)       064003       Lung Margin   18.7   Liver Cancer 1025   7.5       (OD04404)       Lung Cancer   18.0   Liver Cancer 1026   4.4       (OD04565)       Lung Margin   15.1   Liver Cancer   7.5       (OD04565)       6004-T       Lung Cancer   59.9   Liver Tissue   4.8       (OD04237-01)       6004-N       Lung Margin   29.1   Liver Cancer   4.3       (OD04237-02)       6005-T       Ocular Mel Met to   3.3   Liver Tissue 6005-N   1.4       Liver (ODO4310)       Liver Margin   13.6   Normal Bladder   68.8       (ODO4310)       Melanoma Mets to   24.0   Bladder Cancer   1.8       Lung (OD04321)       1023       Lung Margin   32.1   Bladder Cancer   4.1       (OD04321)       A302173       Normal Kidney   11.4   Bladder Cancer   100.0               (OD04718-01)       Kidney Ca, Nuclear   48.0   Bladder Normal   20.9       grade 2 (OD04338)       Adjacent               (OD04718-03)       Kidney Margin   15.6   Normal Ovary   2.6       (OD04338)       Kidney Ca Nuclear   10.1   Ovarian Cancer   32.5       grade 1/2 (OD04339)       064008       Kidney Margin   13.3   Ovarian Cancer   80.1       (OD04339)       (OD04768-07)       Kidney Ca, Clear cell   52.1   Ovary Margin   6.0       type (OD04340)       (OD04768-08)       Kidney Margin   14.1   Normal Stomach   4.5       (OD04340)       Kidney Ca, Nuclear   18.6   Gastric Cancer   0.8       grade 3 (OD04348)       9060358       Kidney Margin   51.4   Stomach Margin   9.3       (OD04348)       9060359       Kidney Cancer   15.8   Gastric Cancer   15.4       (OD04622-01)       9060395       Kidney Margin   2.0   Stomach Margin   9.7       (OD04622-03)       9060394       Kidney Cancer   26.1   Gastric Cancer   23.8       (OD04450-01)       9060397       Kidney Margin   7.7   Stomach Margin   4.0       (OD04450-03)       9060396       Kidney Cancer   3.6   Gastric Cancer   31.6       8120607       064005                    
     [0562]               TABLE CG                          Panel 4.1D                                 Rel. Exp.       Rel. Exp.           (%) Ag3962,       (%) Ag3962,           Run       Run       Tissue Name   170739798   Tissue Name   170739798                                     Secondary Th1 act   26.1   HUVEC IL-1beta   12.2       Secondary Th2 act   100.0   HUVEC IFN gamma   68.3       Secondary Tr1 act   27.7   HUVEC TNF alpha +   50.3               IFN gamma       Secondary Th1 rest   19.3   HUVEC TNF alpha +   22.4               IL4       Secondary Th2 rest   22.1   HUVEC IL-11   5.4       Secondary Tr1 rest   41.5   Lung Microvascular   11.8               EC none       Primary Th1 act   24.8   Lung Microvascular   32.5               EC TNFalpha +               IL-1beta       Primary Th2 act   24.7   Microvascular Dermal   11.8               EC none       Primary Tr1 act   20.4   Microsvasular Dermal   16.8               EC TNFalpha +               IL-1beta       Primary Th1 rest   16.2   Bronchial epithelium   11.8               TNFalpha + IL1beta       Primary Th2 rest   6.1   Small airway   4.4               epithelium none       Primary Tr1 rest   14.8   Small airway   11.7               epithelium                TNFalpha + IL-1beta       CD45RA CD4   39.0   Coronery artery SMC   3.0       lymphocyte act       rest       CD45RO CD4   52.5   Coronery artery SMC   5.8       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   19.3   Astrocytes rest   2.3       Secondary CD8   36.1   Astrocytes   8.3       lymphocyte rest       TNFalpha + IL-1beta       Secondary CD8   9.7   KU-812 (Basophil)   8.9       lymphocyte act       rest       CD4 lymphocyte   11.1   KU-812 (Basophil)   27.0       none       PMA/ionomycin       2ry Th1/Th2/   17.7   CCD1106 (Keratino-   13.3       Tr1_anti-CD95       cytes) none       CH11       LAK cells rest   43.2   CCD1106 (Keratino-   53.6               cytes) TNFalpha +               IL-1beta       LAK cells IL-2   47.3   Liver cirrhosis   4.5       LAK cells IL-2 +   42.0   NCI-H292 none   12.9       IL-12       LAK cells IL-2 +   29.9   NCI-H292 IL-4   25.0       IFN gamma       LAK cells IL-2 +   37.6   NCI-H292 IL-9   26.4       IL-18       LAK cells   51.1   NCI-H292 IL-13   25.5       PMA/ionomycin       NK Cells IL-2 rest   59.9   NCI-H292 IFN   69.3               gamma       Two Way MLR 3   78.5   HPAEC none   9.5       day       Two Way MLR 5   37.1   HPAEC TNF alpha +   37.9       day       IL-1 beta       Two Way MLR 7   16.3   Lung fibroblast none   14.3       day       PBMC rest   12.2   Lung fibroblast TNF   23.0               alpha + IL-1 beta       PBMC PWM   32.3   Lung fibroblast IL-4   11.4       PBMC PHA-L   14.7   Lung fibroblast IL-9   11.9       Ramos (B cell) none   1.5   Lung fibroblast IL-13   13.8       Ramos (B cell)   1.7   Lung fibroblast IFN   84.1       ionomycin       gamma       B lymphocytes   23.3   Dermal fibroblast   11.6       PWM       CCD1070 rest       B lymphocytes   31.2   Dermal fibroblast   25.7       CD40L and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   13.4   Dermal fibroblast   8.7               CCD1070 IL-1 beta       EOL-1 dbcAMP   6.8   Dermal fibroblast IFN   49.3       PMA/ionomycin       gamma       Dendritic cells none   18.0   Dermal fibroblast IL-4   29.3       Dendritic cells LPS   34.4   Dermal Fibroblasts   11.7               rest       Dendritic cells anti-   14.1   Neutrophils TNFa +   4.9       CD40       LPS       Monocytes rest   26.1   Neutrophils rest   18.6       Monocytes LPS   79.0   Colon   3.8       Macrophages rest   21.3   Lung   10.9       Macrophages LPS   40.3   Thymus   13.9       HUVEC none   3.9   Kidney   6.8       HUVEC starved   5.4                    
     [0563]               TABLE CH                          Panel 4D                                 Rel. Exp.       Rel. Exp.           (%) Ag1983,       (%) Ag1983,           Run       Run       Tissue Name   162350741   Tissue Name   1162350741                                     Secondary Th1 act   23.7   HUVEC IL-1beta   1.7       Secondary Th2 act   78.5   HUVEC IFN gamma   76.3       Secondary Tr1 act   37.6   HUVEC TNF alpha +   56.6               IFN gamma       Secondary Th1 rest   25.9   HUVEC TNF alpha +   20.4               IL4       Secondary Th2 rest   20.7   HUVEC IL-11   4.9       Secondary Tr1 rest   20.9   Lung Microvascular   7.9               EC none       Primary Th1 act   13.7   Lung Microvascular   28.7               EC TNFalpha +               IL-1beta       Primary Th2 act   15.1   Microvascular Dermal   10.3               EC none       Primary Tr1 act   16.2   Microsvasular Dermal   27.9               EC TNFalpha +               IL-1beta       Primary Th1 rest   60.3   Bronchial epithelium   20.7               TNFalpha + IL1beta       Primary Th2 rest   19.6   Small airway   2.9               epithelium none       Primary Tr1 rest   20.0   Small airway   13.6               epithelium               TNFalpha + IL-1beta       CD45RA CD4   22.5   Coronery artery SMC   1.9       lymphocyte act       rest       CD45RO CD4   18.0   Coronery artery SMC   2.3       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   15.0   Astrocytes rest   1.8       Secondary CD8   19.9   Astrocytes   6.9       lymphocyte rest       TNFalpha + IL-1beta       Secondary CD8   9.2   KU-812 (Basophil)   7.9       lymphocyte act       rest       CD4 lymphocyte   6.0   KU-812 (Basophil)   18.7       none       PMA/ionomycin       2ry Th1/Th2/   10.7   CCD1106 (Keratino-   10.2       Tr1_anti-CD95       cytes) none       CH11       LAK cells rest   35.1   CCD1106 (Keratino-   60.7               cytes) TNFalpha               + IL-1beta       LAK cells IL-2   37.9   Liver cirrhosis   4.9       LAK cells IL-2 +   41.8   Lupus kidney   2.4       IL-12       LAK cells IL-2 +   63.3   NCI-H292 none   16.2       IFN gamma       LAK cells IL-2 +   46.3   NCI-H292 IL-4   28.5       IL-18       LAK cells   35.1   NCI-H292 IL-9   23.2       PMA/ionomycin       NK Cells IL-2 rest   36.3   NCI-H292 IL-13   26.6       Two Way MLR 3   84.7   NCI-H292 IFN gamma   100.0       day       Two Way MLR 5   37.4   HPAEC none   8.2       day       Two Way MLR 7   17.3   HPAEC TNF alpha +   24.1       day       IL-1 beta       PBMC rest   9.9   Lung fibroblast none   9.6       PBMC PWM   61.1   Lung fibroblast TNF   20.0               alpha + IL-1 beta       PBMC PHA-L   19.9   Lung fibroblast IL-4   17.0       Ramos (B cell) none   1.0   Lung fibroblast IL-9   13.2       Ramos (B cell)   1.4   Lung fibroblast IL-13   17.1       ionomycin       B lymphocytes   78.5   Lung fibroblast IFN   95.3       PWM       gamma       B lymphocytes   73.7   Dermal fibroblast   6.4       CD40L and IL-4       CCD1070 rest       EOL-1 dbcAMP   9.7   Dermal fibroblast   31.6               CCD1070 TNF alpha       EOL-1 dbcAMP   6.2   Dermal fibroblast   11.3       PMA/ionomycin       CCD107O IL-1 beta       Dendritic cells   18.2   Dermal fibroblast IFN   70.2       none       gamma       Dendritic cells LPS   43.5   Dermal fibroblast IL-4   18.4       Dendritic cells anti-   9.8   IBD Colitis 2   3.3       CD40       Monocytes rest   20.9   IBD Crohn&#39;s   2.3       Monocytes LPS   40.3   Colon   17.9       Macrophages rest   18.6   Lung   15.5       Macrophages LPS   33.9   Thymus   7.4       HUVEC none   7.2   Kidney   17.3       HUVEC starved   4.9                    
     [0564]               TABLE CI                          general oncology screening panel_v_2.4                                 Rel. Exp.       Rel. Exp.           (%) Ag3962,       (%) Ag3962,           Run       Run       Tissue Name   268143875   Tissue Name   268143875                                     Colon cancer 1   18.2   Bladder cancer NAT 2   1.1       Colon NAT 1   10.7   Bladder cancer NAT 3   1.8       Colon cancer 2   42.3   Bladder cancer NAT 4   1.7       Colon cancer   11.0   Adenocarcinoma of the   41.2       NAT 2       prostate 1       Colon cancer 3   50.0   Adenocarcinoma of the   3.3               prostate 2       Colon cancer   15.6   Adenocarcinoma of the   6.9       NAT 3       prostate 3       Colon malignant   44.1   Adenocarcinoma of the   14.4       cancer 4       prostate 4       Colon normal   8.5   Prostate cancer NAT 5   4.3       adjacent tissue 4       Lung cancer 1   12.6   Adenocarcinoma of the   7.6               prostate 6       Lung NAT 1   2.1   Adenocarcinoma of the   6.5               prostate 7       Lung cancer 2   29.9   Adenocarcinoma of the   2.0               prostate 8       Lung NAT 2   3.3   Adenocarcinoma of the   29.5               prostate 9       Squamous cell   30.6   Prostate cancer NAT 10   1.6       carcinoma 3       Lung NAT 3   2.3   Kidney cancer 1   17.6       metastatic   15.3   KidneyNAT 1   5.4       melanoma 1       Melanoma 2   2.9   Kidney cancer 2   100.0       Melanoma 3   4.0   Kidney NAT 2   6.2       metastatic   41.5   Kidney cancer 3   20.6       melanoma 4       metastatic   49.3   Kidney NAT 3   2.3       melanoma 5       Bladder cancer 1   10.0   Kidney cancer 4   8.5       Bladder cancer   0.0   Kidney NAT 4   2.9       NAT 1       Bladder cancer 2   4.6                    
     [0565] CNS_neurodegeneration_v1.0 Summary: Ag3692 This panel confirms the expression of the CG94915-01 gene at low levels in the brain in an independent group of individuals. This gene is found to be upregulated in the temporal cortex of Alzheimer&#39;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.  
     [0566] General_screening_panel_v1.4 Summary: Ag3962 Expression of the CG94915-01 gene is highest in a gastric cancer cell line (CT=25). This gene is ubiquitously expressed in this panel, with significant levels of expression also detectable in a cluster of samples derived from ovarian, breast and brain cancer cell lines. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of ovarian, breast, brain, and gastric cancers.  
     [0567] 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.  
     [0568] 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&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0569] In addition, this gene is expressed at much higher levels in fetal liver (CT=28.2) when compared to expression in the adult counterpart (CT=31.4). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.  
     [0570] Panel 1.3D Summary: Ag3962 Expression of the CG94915-01 gene is highest in a gastric cancer cell line (CT=28.8). Overall, expression in this panel is in agreement with expression in Panel 1.4.  
     [0571] Panel 2D Summary: Ag3962 Expression of the CG94915-01 gene is highest in a bladder cancer (CT=28.8). In addition, expression of this gene is higher in bladder cancer than in normal adjacent tissue. Overall, expression of this gene is widespread in this panel. Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of bladder cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of bladder cancer.  
     [0572] Panel 4.1D Summary: Ag3962 Expression of the CG94915-01 gene is highest in chroncically activated Th2 cells (CT=26.2). In addition, 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.  
     [0573] Panel 4D Summary: Ag1983 Expression of the CG94915-01 gene is highest in IFN-gamma activated NCI-H292 cells (CT=28.8). In addition, 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.  
     [0574] general oncology screening panel_v — 2.4 Summary: Ag3962/Ag1983 Expression of the CG94915-01 gene is highest in kidney cancer (CT=26.4). In addition, significant levels of expression are seen in kidney and colon cancers when compared to normal adjacent tissue. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of kidney and colon cancers.  
     D. NOV16a (CG95504-01) and NOV16b (CG95504-02): Syncoilin  
     [0575] Expression of the CG95504-01 and variant CG95504-02 genes were assessed using the primer-probe set Ag4016, described in Table DA. Results of the RTQ-PCR runs are shown in Tables DB, DC and DD.  
               TABLE DA                          Probe Name Ag4016                                             Start   SEQ ID       Primers   Sequences   Length Position   No                                         Forward   5′-aagccttgaacccagaagttac-3′   22   199   97               Probe   TET-5′-tcttcagaggggtccttaaacctcga-3′-TAMRA   26   225   98               Reverse   5′-tgtcctccaggtagagaatgtc-3′   22   252   99                  
 
     [0576]               TABLE DB                          CNS_neurodegeneration_v1.0                                 Rel. Exp.       Rel. Exp.           (%) Ag4016,       (%) Ag4016,           Run       Run       Tissue Name   212392779   Tissue Name   212392779                                     AD 1 Hippo   20.3   Control (Path) 3   14.5               Temporal Ctx       AD 2 Hippo   55.1   Control (Path) 4   25.7               Temporal Ctx       AD 3 Hippo   11.8   AD 1 Occipital Ctx   17.6       AD 4 Hippo   22.4   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   42.9   AD 3 Occipital Ctx   7.7       AD 6 Hippo   100.0   AD 4 Occipital Ctx   26.2       Control 2 Hippo   33.2   AD 5 Occipital ctx   22.4       Control 4 Hippo   57.8   AD 6 Occipital ctx   33.4       Control (Path) 3   17.1   Control 1 Occipital   5.5       Hippo       Ctx       AD 1 Temporal Ctx   44.4   Control 2 Occipital   31.6               Ctx       AD 2 Temporal Ctx   44.4   Control 3 Occipital   22.7               Ctx       AD 3 Temporal Ctx   15.0   Control 4 Occipital   16.6               Ctx       Ad 4 Temporal Ctx   38.4   Control (Path) 1   31.6               Occipital Ctx       AD 5 Inf Temporal   61.1   Control (Path) 2   8.5       Ctx       Occipital Ctx       AD 5 SupTemporal   70.2   Control (Path) 3   8.0       Ctx       Occipital Ctx       AD 6 Inf Temporal   55.1   Control (Path) 4   12.1       Ctx       Occipital Ctx       AD 6 Sup Temporal   64.2   Control 1 Parietal   18.6       Ctx       Ctx       Control 1 Temporal   15.0   Control 2 Parietal   67.4       Ctx       Ctx       Control 2 Temporal   39.8   Control 3 Parietal   15.6       Ctx       Ctx       Control 3 Temporal   21.3   Control (Path) 1   47.6       Ctx       Parietal Ctx       Control 4 Temporal   23.0   Control (Path) 2   27.5       Ctx       Parietal Ctx       Control (Path) 1   56.6   Control (Path) 3   8.3       Temporal Ctx       Parietal Ctx       Control (Path) 2   40.6   Control (Path) 4   33.2       Temporal Ctx       Parietal Ctx                    
     [0577]               TABLE DC                          General_screening_panel_v1.4                                 Rel. Exp.       Rel. Exp.           (%) Ag4016,       (%) Ag4016,           Run       Run       Tissue Name   218425352   Tissue Name   218425352                                     Adipose   1.9   Renal ca. TK-10   1.0       Melanoma*   50.3   Bladder   0.8       Hs688(A).T       Melanoma*   54.0   Gastric ca. (liver met.)   0.2       Hs688(B).T       NCI-N87       Melanoma* M14   3.0   Gastric ca. KATO III   0.3       Melanoma*   1.0   Colon ca. SW-948   0.0       LOXIMVI       Melanoma* SK-   1.1   Colon ca. SW480   0.5       MEL-5       Squamous cell   0.3   Colon ca.* (SW480   0.1       carcinoma SCC-4       met) SW620       Testis Pool   2.1   Colon ca. HT29   0.0       Prostate ca.* (bone   3.3   Colon ca. HCT-116   0.8       met) PC-3       Prostate Pool   2.3   Colon ca. CaCo-2   0.1       Placenta   0.9   Colon cancer tissue   2.2       Uterus Pool   1.3   Colon ca. SW1116   0.1       Ovarian ca.   1.5   Colon ca. Colo-205   0.0       OVCAR-3       Ovarian ca. SK-OV-   3.5   Colon ca. SW-48   0.0       3       Ovarian ca.   4.7   Colon Pool   4.5       OVCAR-4       Ovarian ca.   0.5   Small Intestine Pool   2.0       OVCAR-5       Ovarian ca.   0.8   Stomach Pool   1.2       IGROV-1       Ovarian ca.   0.7   Bone Marrow Pool   2.6       OVCAR-8       Ovary   1.6   Fetal Heart   1.0       Breast ca. MCF-7   0.1   Heart Pool   2.4       Breast ca. MDA-   2.0   Lymph Node Pool   8.2       MB-231       Breast ca. BT 549   39.0   Fetal Skeletal Muscle   6.5       Breast ca. T47D   1.7   Skeletal Muscle Pool   8.4       Breast ca. MDA-N   0.0   Spleen Pool   0.7       Breast Pool   3.5   Thymus Pool   1.2       Trachea   3.2   CNS cancer (glio/   33.0               astro) U87-MG       Lung   0.8   CNS cancer (glio/   97.3               astro) U-118-MG       Fetal Lung   3.3   CNS cancer   0.4               (neuro;met) SK-N-AS       Lung ca. NCI-N417   0.2   CNS cancer (astro)   8.4               SF-539       Lung ca. LX-1   0.3   CNS cancer (astro)   100.0               SNB-75       Lung ca. NCI-H146   0.0   CNS cancer (glio)   0.8               SNB-19       Lung ca. SHP-77   0.1   CNS cancer (glio)   18.6               SF-295       Lung ca. A549   1.9   Brain (Amygdala)   0.5               Pool       Lung ca. NCI-H526   0.0   Brain (cerebellum)   0.8       Lung ca. NCI-H23   0.5   Brain (fetal)   1.3       Lung ca. NCI-H460   0.1   Brain (Hippocampus)   0.8               Pool       Lung ca. HOP-62   1.0   Cerebral Cortex Pool   0.6       Lung ca. NCI-H522   0.1   Brain (Substantia   0.7               nigra) Pool       Liver   0.0   Brain (Thalamus) Pool   1.1       Fetal Liver   0.1   Brain (whole)   0.8       Liver ca. HepG2   0.2   Spinal Cord Pool   1.6       Kidney Pool   8.8   Adrenal Gland   1.1       Fetal Kidney   0.9   Pituitary gland Pool   0.2       Renal ca. 786-0   1.3   Salivary Gland   0.6       Renal ca. A498   2.9   Thyroid (female)   0.8       Renal ca. ACHN   4.2   Pancreatic ca.   0.2               CAPAN2       Renal ca. UO-31   4.4   Pancreas Pool   3.5                    
     [0578]               TABLE DD                          Panel 4.1D                                 Rel. Exp.       Rel. Exp.           (%) Ag4016,       (%) Ag4016,           Run       Run       Tissue Name   171613750   Tissue Name   171613750                                     Secondary Th1 act   0.4   HUVEC IL-1beta   5.3       Secondary Th2 act   0.6   HUVEC IFN gamma   9.7       Secondary Tr1 act   0.7   HUVEC TNF alpha +   4.7               IFN gamma       Secondary Th1   0.3   HUVEC TNF alpha +   1.9               IL4       Secondary Th2 rest   0.3   HUVEC IL-11   5.2       Secondary Tr1 rest   0.3   Lung Microvascular   23.0               EC none       Primary Th1 act   0.1   Lung Microvascular   8.7               EC TNFalpha +               IL-1beta       Primary Th2 act   0.1   Microvascular Dermal   9.0               EC none       Primary Tr1 act   0.0   Microsvasular Dermal   4.5               EC TNFalpha +               IL-1beta       Primary Th1 rest   0.2   Bronchial epithelium   10.9               TNFalpha + IL1beta       Primary Th2 rest   0.0   Small airway   8.0               epithelium none       Primary Tr1 rest   0.3   Small airway   12.2               epithelium               TNFalpha + IL-1beta       CD45RA CD4   24.1   Coronery artery SMC   18.2       lymphocyte act       rest       CD45RO CD4   0.9   Coronery artery SMC   17.8       lymphocyte act       TNFalpha +               IL-1beta       CD8 lymphocyte act   0.7   Astrocytes rest   45.4       Secondary CD8   0.7   Astrocytes   42.6       lymphocyte rest       TNFalpha + IL-1beta       Secondary CD8   0.4   KU-812 (Basophil)   3.7       lymphocyte act       rest       CD4 lymphocyte   0.0   KU-812 (Basophil)   6.0       none       PMA/ionomycin       2ry Th1/Th2/   0.5   CCD1106 (Keratino-   7.9       Tr1_anti-CD95       cytes) none       CH11       LAK cells rest   1.1   CCD1106 (Keratino-   13.5               cytes) TNFalpha +               IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   3.1       LAK cells IL-2 +   0.2   NCI-H292 none   3.0       IL-12       LAK cells IL-2 +   0.3   NCI-H292 IL-4   6.2       IFN gamma       LAK cells IL-2 +   0.2   NCI-H292 IL-9   5.7       IL-18       LAK cells   1.5   NCI-H292 IL-13   4.2       PMA/ionomycin       NK Cells IL-2 rest   0.2   NCI-H292 IFN gamma   4.5       Two Way MLR 3   1.9   HPAEC none   7.7       day       Two Way MLR 5   1.8   HPAEC TNF alpha +   6.9       day       IL-1 beta       Two Way MLR 7   1.9   Lung fibroblast none   32.5       day       PBMC rest   0.3   Lung fibroblast TNF   4.1               alpha + IL-1 beta       PBMC PWM   0.5   Lung fibroblast IL-4   12.1       PBMC PHA-L   0.0   Lung fibroblast IL-9   19.1       Ramos (B cell) none   0.0   Lung fibroblast IL-13   13.3       Ramos (B cell)   0.0   Lung fibroblast IFN   58.6       ionomycin       gamma       B lymphocytes   0.0   Dermal fibroblast   78.5       PWM       CCD1070 rest       B lymphocytes   1.7   Dermal fibroblast   51.1       CD40L and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   0.4   Dermal fibroblast   36.3               CCD1070 IL-1 beta       EOL-1 dbcAMP   0.4   Dermal fibroblast IFN   53.2       PMA/ionomycin       gamma       Dendritic cells none   6.0   Dermal fibroblast IL-4   100.0       Dendritic cells LPS   0.4   Dermal Fibroblasts   67.8               rest       Dendritic cells anti-   4.3   Neutrophils TNFa +   2.6       CD40       LPS       Monocytes rest   0.4   Neutrophils rest   7.6       Monocytes LPS   0.7   Colon   4.9       Macrophages rest   2.6   Lung   5.8       Macrophages LPS   2.6   Thymus   3.6       HUVEC none   4.2   Kidney   12.8       HUVEC starved   7.8                    
     [0579] CNS_neurodegeneration_v1.0 Summary: Ag4016 This panel does not show differential expression of the CG95504-01 gene in Alzheimer&#39;s disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of utility of this gene in the central nervous system.  
     [0580] General_screening_panel_v1.4 Summary: Ag4016 Highest expression of the CG95504-01 gene is seen in a brain cancer cell line (CT=23.6). In addition, significant levels of expression are seen in a cluster of samples derived from brain, breast and melanoma cancer cell lines. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of brain, breast and melanoma cancers.  
     [0581] Among tissues with metabolic function, this gene is expressed at significant levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0582] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. The CG95504-01 gene codes for a homolog of mouse syncoilin. Syncoilin is a member of intermediate filament superfamily that plays a role in the maintenance of the neuromuscular junction and for maturation of the synapses (Newey et al., 2001, J Biol Chem 2001 Mar 2;276(9):6645-55, PMID: 11053421). Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0583] Panel 4.1D Summary: Ag4016 Highest expression of the CG95504-01 gene is seen in IL-4 treated dermal fibroblasts (CT=27.8). Significant levels of expression are also seen in a cluster of treated and untreated dermal fibroblasts. Thus, expression of this gene could be used as a marker of this cell. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of inflammatory lung conditions such as psoriasis.  
     E. NOV17a (CG95589-01) and NOV17b (CG95589-02): Intracellular Protein  
     [0584] Expression of gene CG95589-01 and variant CG95589-02 was assessed using the primer-probe set Ag4349, described in Table EA. Results of the RTQ-PCR runs are shown in Tables EB and EC. Please note that CG95589-02 represents a full-length physical clone of the CG95589-01 gene, validating the prediction of the gene sequence.  
               TABLE EA                          Probe Name Ag4349                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-caggactgtgtgttcagcaa-3′   20   251   100               Probe   TET-5′-atgtgctacgccatcattcaggcag-3′-TAMRA   25   284   101               Reverse   5′-tctggcctgcttgtttactc-3′   20   310   102                  
 
     [0585]               TABLE EB                          General_screening_panel_v1.4                                 Rel. Exp.       Rel. Exp.           (%) Ag4349,       (%) Ag4349,           Run       Run       Tissue Name   222523513   Tissue Name   222523513                                     Adipose   2.5   Renal ca. TK-10   16.6       Melanoma*   5.0   Bladder   8.3       Hs688(A).T       Melanoma*   4.5   Gastric ca. (liver met.)   18.3       Hs688(B).T       NCI-N87       Melanoma* M14   5.7   Gastric ca. KATO III   42.6       Melanoma*   2.3   Colon ca. SW-948   6.8       LOXIMVI       Melanoma* SK-   30.4   Colon ca. SW4 80   42.0       MEL-5       Squamous cell   2.8   Colon ca.* (SW480   33.0       carcinoma SCC-4       met) SW620       Testis Pool   4.4   Colon ca. HT29   10.3       Prostate ca.* (bone   38.2   Colon ca. HCT-116   19.1       met) PC-3       Prostate Pool   1.9   Colon ca. CaCo-2   11.3       Placenta   5.1   Colon cancer tissue   9.3       Uterus Pool   2.1   Colon ca. SW1116   9.6       Ovarian ca.   14.6   Colon ca. Colo-205   14.9       OVCAR-3       Ovarian ca. SK-   30.8   Colon ca. SW-48   13.8       OV-3       Ovarian ca.   8.0   Colon Pool   7.5       OVCAR-4       Ovarian ca.   50.0   Small Intestine Pool   4.5       OVCAR-5       Ovarian ca.   15.3   Stomach Pool   2.9       IGROV-1       Ovarian ca.   15.2   Bone Marrow Pool   2.9       OVCAR-8       Ovary   2.8   Fetal Heart   2.8       Breast ca. MCF-7   15.2   Heart Pool   3.5       Breast ca. MDA-   16.4   Lymph Node Pool   8.2       MB-231       Breast ca. BT 549   8.2   Fetal Skeletal Muscle   2.9       Breast ca. T47D   100.0   Skeletal Muscle Pool   4.9       Breast ca. MDA-N   4.5   Spleen Pool   3.4       Breast Pool   7.6   Thymus Pool   4.5       Trachea   6.3   CNS cancer (glio/   11.8               astro) U87-MG       Lung   0.7   CNS cancer (glio/   18.0               astro) U-118-MG       Fetal Lung   7.7   CNS cancer   20.7               (neuro;met) SK-N-AS       Lung ca. NCI-N417   1.7   CNS cancer (astro)   1.0               SF-539       Lung ca. LX-1   36.1   CNS cancer (astro)   4.5               SNB-75       Lung ca. NCI-H146   3.7   CNS cancer (glio)   14.4               SNB-19       Lung ca. SHP-77   18.7   CNS cancer (glio) SF-   51.8               295       Lung ca. A549   33.4   Brain (Amygdala)   2.9               Pool       Lung ca. NCI-H526   7.1   Brain (cerebellum)   4.1       Lung ca. NCI-H23   14.0   Brain (fetal)   3.7       Lung ca. NCI-H460   17.9   Brain (Hippocampus)   3.5               Pool       Lung ca. HOP-62   11.8   Cerebral Cortex Pool   4.0       Lung ca. NCI-H522   77.9   Brain (Substantia   4.4               nigra) Pool       Liver   1.6   Brain (Thalamus) Pool   4.6       Fetal Liver   5.4   Brain (whole)   4.7       Liver ca. HepG2   8.2   Spinal Cord Pool   4.2       Kidney Pool   9.9   Adrenal Gland   8.6       Fetal Kidney   4.1   Pituitary gland Pool   1.1       Renal ca. 786-0   11.5   Salivary Gland   3.2       Renal ca. A498   3.7   Thyroid (female)   3.8       Renal ca. ACHN   27.2   Pancreatic ca.   16.3               CAPAN2       Renal ca. UO-31   9.0   Pancreas Pool   6.5                    
     [0586]               TABLE EC                          Panel 4.1D                                 Rel. Exp.       Rel. Exp.           (%) Ag4349,       (%) Ag4349,           Run       Run       Tissue Name   186362675   Tissue Name   186362675                                     Secondary Th1 act   57.0   HUVEC IL-1beta   15.7       Secondary Th2 act   79.6   HUVEC IFN gamma   19.9       Secondary Tr1 act   54.3   HUVEC TNF alpha +   9.4               IFN gamma       Secondary Th1 rest   32.8   HUVEC TNF alpha +   13.6               IL4       Secondary Th2 rest   29.7   HUVEC IL-11   12.9       Secondary Tr1 rest   38.2   Lung Microvascular   28.3               EC none       Primary Th1 act   57.4   Lung Microvascular   18.0               EC TNFalpha +               IL-1beta       Primary Th2 act   94.6   Microvascular Dermal   22.7               EC none       Primary Tr1 act   77.9   Microsvasular Dermal   8.1               EC TNFalpha +               IL-1beta       Primary Th1 rest   50.0   Bronchial epithelium   24.8               TNFalpha + IL1beta       Primary Th2 rest   28.1   Small airway   6.4               epithelium none       Primary Tr1 rest   41.5   Small airway   14.6               epithelium               TNFalpha + IL-1beta       CD45RA CD4   51.4   Coronery artery SMC   6.0       lymphocyte act       rest       CD45RO CD4   87.1   Coronery artery SMC   9.7       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   79.6   Astrocytes rest   5.3       Secondary CD8   57.8   Astrocytes   7.0       lymphocyte rest       TNFalpha + IL-1beta       Secondary CD8   56.3   KU-812 (Basophil)   19.8       lymphocyte act       rest       CD4 lymphocyte   14.4   KU-812 (Basophil)   31.4       none       PMA/ionomycin       2ry Th1/Th2/   54.7   CCD1106 (Keratino-   11.9       Tr1_anti-CD95       cytes) none       CH11       LAK cells rest   71.7   CCD1106 (Keratino-   9.5               cytes) TNFalpha +               IL-1beta       LAK cells IL-2   78.5   Liver cirrhosis   5.1       LAK cells IL-2 +   28.5   NCI-H292 none   49.3       IL-12       LAK cells IL-2 +   33.2   NCI-H292 IL-4   55.1       IFN gamma       LAK cells IL-2 +   42.3   NCI-H292 IL-9   100.0       IL-18       LAK cells   33.0   NCI-H292 IL-13   40.6       PMA/ionomycin       NK Cells IL-2 rest   99.3   NCI-H292 IFN gamma   67.8       Two Way MLR 3   49.7   HPAEC none   17.3       day       Two Way MLR 5   46.0   HPAEC TNF alpha +   14.5       day       IL-1 beta       Two Way MLR 7   55.5   Lung fibroblast none   12.8       day       PBMC rest   29.3   Lung fibroblast TNF   7.2               alpha + IL-1 beta       PBMC PWM   45.1   Lung fibroblast IL-4   7.3       PBMC PHA-L   73.2   Lung fibroblast IL-9   11.9       Ramos (B cell) none   70.7   Lung fibroblast IL-13   7.3       Ramos (B cell)   92.7   Lung fibroblast IFN   9.0       ionomycin       gamma       B lymphocytes   52.5   Dermal fibroblast   18.7       PWM       CCD1070 rest       B lymphocytes   97.3   Dermal fibroblast   69.7       CD40L and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   31.0   Dermal fibroblast   5.1               CCD1070 IL-1 beta       EOL-1 dbcAMP   5.4   Dermal fibroblast IFN   6.9       PMA/ionomycin       gamma       Dendritic cells none   57.4   Dermal fibroblast IL-4   18.3       Dendritic cells LPS   38.4   Dermal Fibroblasts   10.7               rest       Dendritic cells anti-   66.0   Neutrophils TNFa +   3.5       CD40       LPS       Monocytes rest   74.7   Neutrophils rest   5.2       Monocytes LPS   13.3   Colon   14.9       Macrophages rest   38.7   Lung   25.2       Macrophages LPS   23.2   Thymus   29.3       HUVEC none   11.3   Kidney   24.5       HUVEC starved   20.3                    
     [0587] General_screening_panel_v1.4 Summary: Ag4349 Expression of the CG95589-01 gene is most prominent in cancer cell lines, with highest expression in a breast cancer cell line (CT=26.7). In addition significant levels of expression are seen in all the cancer cell lines on this panel. Higher levels of expression are also seen in fetal lung (CT=30.4) when compared to expression in adult lung (CT=33.8). Since cell lines and tissues are generally more proliferative than tissues, this expression profile suggests that this gene might be involved in cell proliferation. Therefore, inhibition of expression or function of this gene may be a therapeutic avenue for the treatment of cancer or other disease that involve cell proliferation. Furthermore, therapeutic targeting of this gene product with a monoclonal antibody is anticipated to limit or block the extent of tumor cell migration and invasion and tumor metastasis, particularly in melanomas, prostate cancers, pancreatic cancers, ovarian cancers, renal cell carcinomas and CNS cancers. This gene might also be an effective marker for the diagnosis and detection of a variety of cancers.  
     [0588] In addition, expression of this gene could be used to differentiate fetal and adult lung tissue.  
     [0589] 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.  
     [0590] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0591] Panel 4.1D Summary: Ag4349 Expression of the CG95589-01 gene is ubiquitous in this panel. Highest expression is seen in IL-9 treated NCI-H292 cells (CT=29.3). Significant levels of expression are also seen in a cluster of treated and untreated NCI-H292 cells, and in lymphocytes, which is consistent with the expression profile in panel 1.3 where the transcript is expressed in the thymus and lymph node. The transcript is expressed in resting T cells and T cells, both acutely and chronically stimulated. Likewise, stimulated B cells and RAMOS cells express the transcript. Therefore, therapeutics designed with this sequence or the protein it encodes could be important in regulating T cell activation and be important for immune modulation and in treating T cell and B cell mediated diseases such as asthma, allergy, COPD, arthritis, psoriasis. lupus and IBD.  
     F. NOV18a (CG95598-01): Intracellular Protein  
     [0592] Expression of full length clone CG95598-01 was assessed using the primer-probe set Ag4050, described in Table FA. Results of the RTQ-PCR runs are shown in Tables FB, FC and FD.  
               TABLE FA                          Probe Name Ag4050                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ctgctgctgtgtcatctccta-3′   21   451   103               Probe   TET-5′-ccaggaccaggacccagacttca-3′-TAMRA   23   487   104               Reverse   5′-cactgtgtgagccacatttgt-3′   21   510   105                  
 
     [0593]               TABLE FB                          General_screening_panel_v1.4                                 Rel. Exp.       Rel. Exp.           (%) Ag4050,       (%) Ag4050,           Run       Run       Tissue Name   218712972   Tissue Name   218712972                                     Adipose   0.0   Renal ca. TK-10   5.9       Melanoma*   0.5   Bladder   0.3       Hs688(A).T       Melanoma*   0.0   Gastric ca. (liver met.)   100.0       Hs688(B).T       NCI-N87       Melanoma* M14   0.6   Gastric ca. KATO III   9.8       Melanoma*   0.9   Colon ca. SW-948   7.7       LOXIMVI       Melanoma* SK-   0.6   Colon ca. SW480   12.4       MEL-5       Squamous cell   3.9   Colon ca.* (SW480   0.8       carcinoma SCC-4       met) SW620       Testis Pool   0.0   Colon ca. HT29   1.3       Prostate ca.* (bone   2.4   Colon ca. HCT-116   5.9       met) PC-3       Prostate Pool   0.5   Colon ca. CaCo-2   1.9       Placenta   0.6   Colon cancer tissue   14.8       Uterus Pool   0.3   Colon ca. SW1116   4.2       Ovarian ca.   4.3   Colon ca. Colo-205   0.2       OVCAR-3       Ovarian ca. SK-   0.9   Colon ca. SW-48   0.3       OV-3       Ovarian ca.   0.5   Colon Pool   0.5       OVCAR 4       Ovarian ca.   8.4   Small Intestine Pool   0.5       OVCAR-5       Ovarian ca.    0.9   Stomach Pool   0.0       IGROV-1       Ovarian ca.   3.7   Bone Marrow Pool   1.4       OVCAR-8       Ovary   0.0   Fetal Heart   0.0       Breast ca. MCF-7   4.6   Heart Pool   0.2       Breast ca. MDA-   6.2   Lymph Node Pool   0.2       MB-231       Breast ca. BT 549   0.9   Fetal Skeletal Muscle   0.4       Breast ca. T47D   28.3   Skeletal Muscle Pool   0.0       Breast ca. MDA-N   0.6   Spleen Pool   0.2       Breast Pool   0.2   Thymus Pool   0.6       Trachea   0.9   CNS cancer (glio/   3.8               astro) U87-MG       Lung   0.0   CNS cancer (glio/   4.1               astro) U-118-MG       Fetal Lung   0.6   CNS cancer   1.0               (neuro;met) SK-N-AS       Lung ca. NCI-   0.6   CNS cancer (astro)   0.5       N417       SF-539       Lung ca. LX-1   8.8   CNS cancer (astro   4.0               SNB-75       Lung ca. NCI-H146   0.0   CNS cancer (glio)   1.0               SNB-19       Lung ca. SHP-77   1.4   CNS cancer (glio)   6.0               SF-295       Lung ca. A549   0.9   Brain (Amygdala)   0.3               Pool       Lung ca. NCI-H526   0.2   Brain (cerebellum)   0.4       Lung ca. NCI-H23   1.2   Brain (fetal)   0.8       Lung ca. NCI-H460   1.5   Brain (Hippocampus)   0.5               Pool       Lung ca. HOP-62   0.5   Cerebral Cortex Pool   0.8       Lung ca. NCI-H522   2.6   Brain (Substantia   0.5               nigra) Pool       Liver   0.0   Brain (Thalamus) Pool   0.5       Fetal Liver   0.3   Brain (whole)   0.4       Liver ca. HepG2   3.0   Spinal Cord Pool   0.9       Kidney Pool   0.7   Adrenal Gland   0.2       Fetal Kidney   2.2   Pituitary gland Pool   0.4       Renal ca. 786-0   2.4   Salivary Gland   0.4       Renal ca. A498   2.2   Thyroid (female)   0.5       Renal ca. ACHN   0.4   Pancreatic ca.   21.6               CAPAN2       Renal ca. UO-31   0.0   Pancreas Pool   0.4                    
     [0594]               TABLE FC                          Panel 4.1D                                 Rel. Exp.       Rel. Exp.           (%) Ag4050,       (%) Ag4059,           Run       Run       Tissue Name   171619887   Tissue Name   171619887                                     Secondary Th1 act   0.5   HUVEC IL-1 beta   1.1       Secondary Th2 act   3.5   HUVEC IFN gamma   0.0       Secondary Tr1 act   0.7   HUVEC TNF alpha +   0.0               IFN gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha +   0.0               IL4       Secondary Th2 rest   0.0   HUVEC IL-11   0.0       Secondary Tr1 rest   2.6   Lung Microvascular   0.0               EC none       Primary Th1 act   0.0   Lung Microvascular   1.7               EC TNFalpha +               IL-1beta       Primary Th2 act   0.0   Microvascular Dermal   0.9               EC none       Primary Tr1 act   0.0   Microsvasular Dermal   0.0               EC TNFalpha +               IL-1beta       Primary Th1 rest   1.7   Bronchial epithelium   5.0               TNFalpha + IL1beta       Primary Th2 rest   1.1   Small airway   17.2               epithelium none       Primary Tr1 rest   0.0   Small airway   4.9               epithelium               TNFalpha + IL-1beta       CD45RA CD4   2.0   Coronery artery SMC   0.0       lymphocyte act       rest       CD45RO CD4   1.7   Coronery artery SMC   2.6       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   1.7   Astrocytes rest   1.3       Secondary CD8   0.0   Astrocytes   0.0       lymphocyte rest       TNFalpha + IL-1beta       Secondary CD8   1.7   KU-812 (Basophil)   1.0       lymphocyte act       rest       CD4 lymphocyte   0.0   KU-812 (Basophil)   2.9       none       PMA/ionomycin       2ry Th1/Th2/   0.0   CCD1106 (Keratino-   5.6       Tr1_anti-CD95       cytes) none       CH11       LAK cells rest   0.5   CCD1106 (Keratino-   5.4               cytes) TNFalpha +               IL-1beta       LAK cells IL-2   3.1   Liver cirrhosis   1.4       LAK cells IL-2 +   0.0   NCI-H292 none   86.5       IL-12       LAK cells IL-2 +   0.0   NCI-H292 IL-4   97.9       IFN gamma       LAK cells IL-2 +   0.0   NCI-H292 IL-9   88.3       IL-18       LAK cells   0.0   NCI-H292 IL-13   43.2       PMA/ionomycin       NK Cells IL-2 rest   0.0   NCI-H292 IFN gamma   100.0       Two Way MLR 3   0.0   HPAEC none   0.6       day       Two Way MLR 5   0.0   HPAEC TNF alpha +   2.5       day       IL-1 beta       Two Way MLR 7   0.0   Lung fibroblast none   5.1       day       PBMC rest   0.0   Lung fibroblast   0.0               TNF alpha + IL-1 beta       PBMC PWM   0.0   Lung fibroblast IL-4   3.5       PBMC PHA-L   2.9   Lung fibroblast IL-9   1.5       Ramos (B cell)   1.8   Lung fibroblast IL-13   2.0       none       Ramos (B cell)   5.1   Lung fibroblast IFN   4.0       ionomycin       gamma       B lymphocytes   0.0   Dermal fibroblast   3.7       PWM       CCD1070 rest       B lymphocytes   0.0   Dermal fibroblast   0.5       CD40L and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast   1.3               CCD1070 IL-1 beta       EOL-1 dbcAMP   0.0   Dermal fibroblast IFN   1.8       PMA/ionomycin       gamma       Dendritic cells none   1.4   Dermal fibroblast IL-4   3.3       Dendritic cells LPS   1.6   Dermal Fibroblasts   6.2               rest       Dendritic cells anti-   5.9   Neutrophils TNFa +   0.0       CD40       LPS       Monocytes rest   1.7   Neutrophils rest   0.0       Monocytes LPS   2.7   Colon   1.2       Macrophages rest   2.7   Lung   0.0       Macrophages LPS   0.0   Thymus   5.6       HUVEC none   0.0   Kidney   51.4       HUVEC starved   2.0                    
     [0595]               TABLE FD                          general oncology screening panel_v_2.4                                 Rel. Exp.       Rel. Exp.           (%) Ag4050,       (%) Ag4050,           Run       Run       Tissue Name   268362946   Tissue Name   268362946                                     Colon cancer 1   0.8   Bladder cancer NAT 2   0.0       Colon cancer   0.0   Bladder cancer NAT 3   0.0       NAT 1       Colon cancer 2   75.3   Bladder cancer NAT 4   0.0       Colon cancer   0.0   Adenocarcinoma of the   1.4       NAT 2       prostate 1       Colon cancer 3   1.3   Adenocarcinoma of the   0.0               prostate 2       Colon cancer   0.9   Adenocarcinoma of the   1.2       NAT 3       prostate 3       Colon malignant   14.5   Adenocarcinoma of the   4.7       cancer 4       prostate 4       Colon normal   0.0   Prostate cancer NAT 5   1.4       adjacent tissue 4       Lung cancer 1   6.5   Adenocarcinoma of the   2.3               prostate 6       Lung NAT 1   0.0   Adenocarcinoma of the   2.2               prostate 7       Lung cancer 2   10.2   Adenocarcinoma of the   0.0               prostate 8       Lung NAT 2   0.5   Adenocarcinoma of the   1.8               prostate 9       Squamous cell   1.0   Prostate cancer NAT 10   0.8       carcinoma 3       Lung NAT 3   0.0   Kidney cancer 1   0.0       metastatic   0.0   Kidney NAT 1   8.8       melanoma 1       Melanoma 2   100.0   Kidney cancer 2   10.4       Melanoma 3   28.1   Kidney NAT 2   8.8       metastatic   2.4   Kidney cancer 3   3.9       melanoma 4       metastatic   1.4   Kidney NAT 3   4.9       melanoma 5       Bladder cancer 1   1.1   Kidney cancer 4   1.1       Bladder cancer   0.0   Kidney NAT 4   3.3       NAT 1       Bladder cancer 2   3.2                    
     [0596] General_screening_panel_v1.4 Summary: Ag4050 Highest expression of the CG95598-01 gene is seen in a gastric cancer cell line (CT=29.5). Significant expression in this panel is limited to cancer cell lines including sampels derived from pancreatic, brain, colon, breast and ovarian cancers. Thus, expression of this gene could be used as a marker of cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of cancer.  
     [0597] Panel 4.1D Summary: Ag4050 Highest expression of the CG95598-01 gene is seen in IFN-gamma treated NCI-H292 cells (CT=31.9). Significant levels of expression are limited to a cluster of both treated and untreated NCI-H292 cells and small airway epithelium. Treatment of these cells does not seem to significantly alter expression of this transcript in this muco-epidermoid cell line. Thus, the protein could be used to identify certain lung tumors similar to NCI-H292. The encoded protein may also contribute to the normal function of the goblet cells within the lung. Therefore, designing therapeutics to this protein may be important for the treatment of emphysema and asthma as well as other lung diseases in which goblet cells or the mucus they produce have pathological consequences.  
     [0598] Moderate expression of this gene is also observed in normal kidney. Therefore, therapeutic modulation of this gene product may also be useful in the treatment of autoimmune and inflammatory diseases that affect kidney including lupus and glomerulonephritis.  
     [0599] general oncology screening panel_v — 2.4 Summary: Ag4050 Expression of the CG95598-01 gene is restricted to a samples derived from colon cancer and melanoma (CTs=31.8-32.4). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of colon cancer and melanoma. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon cancer and melanoma.  
     G. NOV19a (CG95639-01): Von Ebner&#39;s Gland Protein Precursor  
     [0600] Expression of gene CG95639-01 was assessed using the primer-probe set Ag4025, described in Table GA. Results of the RTQ-PCR runs are shown in Tables GB and GC.  
               TABLE GA                          Probe Name Ag4025                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-cacccatgaccctcacaat-3′   19   164   106               Probe   TET-5′-caacctggaagctaaggccaccatg-3′-TAMRA   25   195   107               Reverse   5′-ggcactggccacttatcag-3′   19   220   108                  
 
     [0601]               TABLE GB                          General_screening_panel_v1.4                                 Rel. Exp.       Rel. Exp.           (%) Ag4025,       (%) Ag4025,           Run       Run       Tissue Name   218425730   Tissue Name   218425730                                     Adipose   7.6   Renal ca. TK-10   0.0       Melanoma*   0.0   Bladder   10.1       Hs688(A).T       Melanoma*   0.0   Gastric ca. (liver met.)   100.0       Hs688(B).T       NCI-N87       Melanoma* M14   0.0   Gastric ca. KATO III   11.0       Melanoma*   0.0   Colon ca. SW-948   2.9       LOXIMVI       Melanoma* SK-   0.0   Colon ca. SW480   0.0       MEL-5       Squamous cell   1.6   Colon ca.* (SW480   0.0       carcinoma SCC-4       met) SW620       Testis Pool   10.4   Colon ca. HT29   0.0       Prostate ca.* (bone   0.0   Colon ca. HCT-116   2.7       met) PC-3       Prostate Pool   0.0   Colon ca. CaCo-2   0.0       Placenta   2.8   Colon cancer tissue   2.6       Uterus Pool   4.1   Colon ca. SW1116   2.3       Ovarian ca.   0.0   Colon ca. Colo-205   0.0       OVCAR-3       Ovarian ca. SK-   0.0   Colon ca. SW-48   0.0       OV-3       Ovarian ca.   0.0   Colon Pool   6.6       OVCAR-4       Ovarian ca.   0.0   Small Intestine Pool   0.0       OVCAR-5       Ovarian ca.   0.0   Stomach Pool   6.3       IGROV-1       Ovarian ca.   2.2   Bone Marrow Pool   6.7       OVCAR-8       Ovary   3.1   Fetal Heart   1.7       Breast ca. MCF-7   0.0   Heart Pool   0.0       Breast ca. MDA-   0.0   Lymph Node Pool   12.7       MB-231       Breast ca. BT 549   0.0   Fetal Skeletal Muscle   3.0       Breast ca. T47D   6.7   Skeletal Muscle Pool   2.5       Breast ca. MDA-N   0.0   Spleen Pool   0.0       Breast Pool   3.5   Thymus Pool   1.5       Trachea   0.0   CNS cancer (glio/   0.0               astro) U87-MG       Lung   30.1   CNS cancer (glio/   0.0               astro) U-118-MG       Fetal Lung   6.6   CNS cancer   0.0               (neuro;met) SK-N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro)   0.0               SF-539       Lung ca. LX-1   58.6   CNS cancer (astro)   0.0               SNB-75       Lung ca. NCI-H146   0.0   CNS cancer (glio)   0.0               SNB-19       Lung ca. SHP-77   0.0   CNS cancer (glio) SF-   0.0               295       Lung ca. A549   0.0   Brain (Amygdala)   2.7               Pool       Lung ca. NCI-H526   0.0   Brain (cerebellum)   0.0       Lung ca. NCI-H23   0.0   Brain (fetal)   0.0       Lung ca. NCI-H460   0.0   Brain (Hippocampus)   6.6               Pool       Lung ca. HOP-62   0.0   Cerebral Cortex Pool   2.5       Lung ca. NCI-H522   0.0   Brain (Substantia   12.0               nigra) Pool       Liver   0.0   Brain (Thalamus) Pool   1.5       Fetal Liver   0.0   Brain (whole)   9.5       Liver ca. HepG2   0.0   Spinal Cord Pool   0.0       Kidney Pool   13.8   Adrenal Gland   0.0       Fetal Kidney   11.3   Pituitary gland Pool   3.0       Renal ca. 786-0   0.0   Salivary Gland   0.0       Renal ca. A498   0.0   Thyroid (female)   0.0       Renal ca. ACHN   6.0   Pancreatic ca.   15.3               CAPAN2       Renal ca. UO-31   0.0   Pancreas Pool   8.3                    
     [0602]               TABLE GC                          general oncology screening panel_v_2.4                                 Rel. Exp.       Rel. Exp.           (%) Ag4025,       (%) Ag4025,           Run       Run       Tissue Name   268362900   Tissue Name   268362900                                     Colon cancer 1   2.8   Bladder cancer NAT 2   0.0       Colon cancer   0.0   Bladder cancer NAT 3   2.0       NAT 1       Colon cancer 2   0.0   Bladder cancer NAT 4   0.0       Colon cancer   0.0   Adenocarcinoma of the   6.3       NAT 2       prostate 1       Colon cancer 3   0.0   Adenocarcinoma of the   0.0               prostate 2       Colon cancer   3.2   Adenocarcinoma of the   2.4       NAT 3       prostate 3       Colon malignant   2.9   Adenocarcinoma of the   2.5       cancer 4       prostate 4       Colon normal   0.0   Prostate cancer NAT 5   0.0       adjacent tissue 4       Lung cancer 1   0.0   Adenocarcinoma of the   0.0               prostate 6       Lung NAT 1   2.4   Adenocarcinoma of the   6.0               prostate 7       Lung cancer 2   7.5   Adenocarcinoma of the   0.0               prostate 8       Lung NAT 2   2.0   Adenocarcinoma of the   0.0               prostate 9       Squamous cell   10.2   Prostate cancer NAT   0.0       carcinoma 3       10       Lung NAT 3   0.0   Kidney cancer 1   5.1       metastatic   14.7   KidneyNAT 1   0.0       melanoma 1       Melanoma 2   0.0   Kidney cancer 2   2.5       Melanoma 3   0.0   Kidney NAT 2   0.0       metastatic   59.0   Kidney cancer 3   7.3       melanoma 4       metastatic   100.0   Kidney NAT 3   6.0       melanoma 5       Bladder cancer 1   0.0   Kidney cancer 4   0.0       Bladder cancer   0.0   Kidney NAT 4   3.2       NAT 1       Bladder cancer 2   3.2                    
     [0603] General_screening_panel_v1.4 Summary: Ag4025 Expression of the CG95639-01 gene is highest in a gastric cancer cell line (CT=31.3). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of gastric cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of gastric cancer.  
     [0604] In addition, low but significant levels of expression in the pancreas suggest that this gene product may be involved in the pathogenesis and/or diagnosis of diabetes.  
     [0605] Low levels of expression in the whole brain and substantia nigra show that this gene is also present in the brain and may be involved in neurological disorders including Parkinson&#39;s.  
     [0606] general oncology screening panel_v — 2.4 Summary: Ag4025 Expression of the CG95639-01 gene is restricted to samples derived from melanoma (CTs=33.5-34.3). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of melanoma cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of melanoma cancer.  
     H. NOV21a (CG95775-01): Clathrin Coat Associated Protein  
     [0607] Expression of gene CG95775-01 was assessed using the primer-probe set Ag4100, described in Table HA. Results of the RTQ-PCR runs are shown in Tables HB, HC, HD, HE and HF.  
               TABLE HA                          Probe Name Ag4100                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ccgactatctgacctcacagtt-3′   22   1911   109               Probe   TET-5′-ctatgccctcaactacagcctccgg-3′-TAMRA   25   1933   110               Reverse   5′-gtcagcacatccaggatgtc-3′   20   1967   111                  
 
     [0608]               TABLE HB                          CNS_neurodegeneration_v1.0                                 Rel. Exp.       Rel. Exp.           (%) Ag4100,       (%) Ag4100,           Run       Run       Tissue Name   214296166   Tissue Name   214296166                                     AD 1 Hippo   7.9   Control (Path) 3   11.7               Temporal Ctx       AD 2 Hippo   25.2   Control (Path) 4   18.3               Temporal Ctx       AD 3 Hippo   11.5   AD 1 Occipital Ctx   9.5       AD 4 Hippo   11.5   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   87.7   AD 3 Occipital Ctx   12.6       AD 6 Hippo   23.3   AD 4 Occipital Ctx   9.0       Control 2 Hippo   18.2   AD 5 Occipital Ctx   4.8       Control 4 Hippo   31.6   AD 6 Occipital Ctx   20.6       Control (Path) 3   8.0   Control 1 Occipital   4.5       Hippo       Ctx       AD 1 Temporal Ctx   20.2   Control 2 Occipital   45.7               Ctx       AD 2 Temporal Ctx   11.2   Control 3 Occipital   7.3               Ctx       AD 3 Temporal Ctx   7.4   Control 4 Occipital   6.1               Ctx       AD 4 Temporal Ctx   3.7   Control (Path) 1   45.1               Occipital Ctx       AD 5 Inf Temporal   33.7   Control (Path) 2   8.7       Ctx       Occipital Ctx       AD 5 SupTemporal   24.3   Control (Path) 3   1.9       Ctx       Occipital Ctx       AD 6 Inf Temporal   24.1   Control (Path) 4   14.4       Ctx       Occipital Ctx       AD 6 Sup Temporal   19.2   Control 1 Parietal   11.6       Ctx       Ctx       Control 1 Temporal   8.2   Control 2 Parietal   30.8       Ctx       Ctx       Control 2 Temporal   21.8   Control 3 Parietal   12.7       Ctx       Ctx       Control 3 Temporal   11.2   Control (Path) 1   100.0       Ctx       Parietal Ctx       Control 4 Temporal   12.3   Control (Path) 2   8.2       Ctx       Parietal Ctx       Control (Path) 1   29.1   Control (Path) 3   12.6       Temporal Ctx       Parietal Ctx       Control (Path) 2   15.1   Control (Path) 4   32.3       Temporal Ctx       Parietal Ctx                    
     [0609]               TABLE HC                          General_screening_panel_v1.4                                 Rel. Exp.       Rel. Exp.           (%) Ag4100,       (%) Ag4100,           Run       Run       Tissue Name   219922656   Tissue Name   219922656                                     Adipose   0.7   Renal ca. TK-10   7.4       Melanoma*   2.1   Bladder   5.6       Hs688(A).T       Melanoma*   3.2   Gastric ca. (liver met.)   6.2       Hs688(B).T       NCI-N87       Melanoma* M14   11.2   Gastric ca. KATO III   21.2       Melanoma*   4.5   Colon ca. SW-948   13.6       LOXIMVI       Melanoma* SK-   4.5   Colon ca. SW480   16.7       MEL-5       Squamous Cell   5.7   Colon ca.* (SW480   6.7       carcinoma SCC-4       met) SW620       Testis Pool   1.3   Colon ca. HT29   7.3       Prostate ca.* (bone   2.3   Colon ca. HCT-116   23.3       met) PC-3       Prostate Pool   2.4   Colon ca. CaCo-2   8.0       Placenta   1.7   Colon cancer tissue   8.2       Uterus Pool   0.2   Colon ca. SW1116   10.7       Ovarian ca.   5.3   Colon ca. Colo-205   6.4       OVCAR-3       Ovarian ca. SK-OV-   25.2   Colon ca. SW-48   14.4       3       Ovarian ca.   8.2   Colon Pool   1.9       OVCAR-4       Ovarian ca.   26.4   Small Intestine Pool   2.8       OVCAR-5       Ovarian ca.   19.6   Stomach Pool   1.1       IGROV-1       Ovarian ca.   19.9   Bone Marrow Pool   0.8       OVCAR-8       Ovary   2.9   Fetal Heart   1.8       Breast ca. MCF-7   15.5   Heart Pool   1.5       Breast ca. MDA-   13.4   Lymph Node Pool   2.2       MB-231       Breast ca. BT 549   7.3   Fetal Skeletal Muscle   0.8       Breast ca. T47D   100.0   Skeletal Muscle Pool   3.8       Breast ca. MDA-N   12.9   Spleen Pool   4.0       Breast Pool   2.0   Thymus Pool   4.2       Trachea   1.3   CNS cancer (glio/   6.4               astro) U87-MG       Lung   0.5   CNS cancer (glio/   31.6               astro) U-118-MG       Fetal Lung   2.4   CNS cancer   6.8               (neuro;met) SK-N-AS       Lung ca. NCI-   11.7   CNS cancer (astro)   6.2       N417       SF-539       Lung ca. LX-1   7.6   CNS cancer (astro)   16.5               SNB-75       Lung ca. NCI-H146   8.5   CNS cancer (glio)   18.9               SNB-19       Lung ca. SHP-77   5.6   CNS cancer (glio) SF-   10.0               295       Lung ca. A549   9.0   Brain (Amygdala)   2.8               Pool       Lung ca. NCI-H526   8.6   Brain (cerebellum)   5.8       Lung ca. NCI-H23   4.4   Brain (fetal)   2.8       Lung ca. NCI-H460   3.4   Pool (Hippocampus)   1.8               Pool       Lung ca. HOP-62   2.6   Cerebral Cortex Pool   2.7       Lung ca. NCI-H522   3.6   Brain (Substantia   5.6               nigra) Pool       Liver   0.2   Brain (Thalamus) Pool   2.9       Fetal Liver   1.7   Brain (whole)   1.3       Liver ca. HepG2   5.0   Spinal Cord Pool   4.1       Kidney Pool   2.7   Adrenal Gland   2.4       Fetal Kidney   1.7   Pituitary gland Pool   1.0       Renal ca. 786-0   5.2   Salivary Gland   0.7       Renal ca. A498   2.8   Thyroid (female)   2.3       Renal ca. ACHN   4.3   Pancreatic ca.   6.8               CAPAN2       Renal ca. UO-31   6.4   Pancreas Pool   2.9                    
     [0610]               TABLE HD                          Panel 4.1D                                 Rel. Exp.       Rel. Exp.           (%) Ag4100,       (%) Ag4100,           Run       Run       Tissue Name   172775146   Tissue Name   172775146                                     Secondary Th1 act   39.8   HUVEC IL-1beta   40.6       Secondary Th2 act   59.5   HUVEC IFN gamma   33.2       Secondary Tr1 act   64.2   HUVEC TNF alpha +   38.2               IFN gamma       Secondary Th1 rest   15.7   HUVEC TNF alpha +   49.7           IL4       Secondary Th2 rest   22.7   HUVEC IL-11   29.7       Secondary Tr1 rest   21.8   Lung Microvascular   87.7               EC none       Primary Th1 act   90.1   Lung Microvascular   46.3               EC               TNFalpha + IL-1beta       Primary Th2 act   64.6   Microvascular Dermal   71.2               EC none       Primary Tr1 act   97.3   Microsvasular Dermal   45.7               EC TNFalpha +               IL-1beta       Primary Th1 rest   25.0   Bronchial epithelium   21.9               TNFalpha + IL1beta       Primary Th2 rest   11.2   Small airway   7.2               epithelium none       Primary Tr1 rest   49.3   Small airway   16.2               epithelium               TNFalpha + IL-1beta       CD45RA CD4   70.7   Coronery artery SMC   12.3       lymphocyte act       rest       CD45RO CD4   93.3   Coronery artery SMC   14.5       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   79.0   Astrocytes rest   19.8       Secondary CD8   63.7   Astrocytes   18.4       lymphocyte rest       TNFalpha +               IL-1beta       Secondary CD8   17.4   KU-812 (Basophil)   43.2       lymphocyte act       rest       CD4 lymphocyte   5.3   KU-812 (Basophil)   19.6       none       PMA/ionomycin       2ry Th1/Th2/   28.1   CCD1106 (Keratino-   92.7       Tr1_anti-CD95       cytes) none       CH11       LAK cells rest   34.6   CCD1106 (Keratino-   47.0               cytes) TNFalpha +               IL-1beta       LAK cells IL-2   24.8   Liver cirrhosis   10.2       LAK cells IL-2 +   36.9   NCI-H292 none   50.0       IL-12       LAK cells IL-2 +   32.8   NCI-H292 IL-4   44.4       IFN gamma       LAK cells IL-2 +   27.9   NCI-H292 IL-9   72.7       IL-18       LAK cells   23.8   NCI-H292 IL-13   57.0       PMA/ionomycin       NK Cells IL-2   40.3   NCI-H292 IFN gamma   66.9       rest       Two Way MLR 3   62.9   HPAEC none   37.6       day       Two Way MLR 5   44.8   HPAEC TNF alpha +   43.5       day       IL-1 beta       Two Way MLR 7   37.4   Lung fibroblast none   22.8       day       PBMC rest   18.0   Lung fibroblast TNF   23.7               alpha + IL-1 beta       PBMC PWM   81.8   Lung fibroblast IL-4   42.0       PBMC PHA-L   51.4   Lung fibroblast IL-9   87.1       Ramos (B cell) none   100.0   Lung fibroblast IL-13   45.4       Ramos (B cell)   98.6   Lung fibroblast IFN   37.4       ionomycin       gamma       B lymphocytes   32.3   Dermal fibroblast   62.4       PWM       CCD1070 rest       B lymphocytes   67.4   Dermal fibroblast   61.6       CD40L and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   51.1   Dermal fibroblast   52.5               CCD1070 IL-1 beta       EOL-1 dbcAMP   27.0   Dermal fibroblast IFN   33.2       PMA/ionomycin       gamma       Dendritic cells none   33.9   Dermal fibroblast IL-4   34.4       Dendritic cells LPS   17.0   Dermal Fibroblasts   20.2               rest       Dendritic cells anti-   17.8   Neutrophils TNFa +   5.0       CD40       LPS       Monocytes rest   15.0   Neutrophils rest   1.3       Monocytes LPS   42.6   Colon   16.7       Macrophages rest   42.9   Lung   13.8       Macrophages LPS   17.7   Thymus   23.8       HUVEC none   55.5   Kidney   36.9       HUVEC starved   71.2                    
     [0611]               TABLE HE                          Panel CNS_1                                 Rel. Exp.       Rel. Exp.           (%) Ag4100,       (%) Ag4100,           Run       Run       Tissue Name   180912027   Tissue Name   180912027                                     BA4 Control   9.1   BA17 PSP   4.7       BA4 Control2   62.0   BA17 PSP2   0.0       BA4   3.1   Sub Nigra Control   26.8       Alzheimer&#39;s2       BA4 Parkinson&#39;s   87.7   Sub Nigra Control2   41.8       BA4   47.0   Sub Nigra   3.0       Parkinson&#39;s2       Alzheimer&#39;s2       BA4   34.4   Sub Nigra   68.3       Huntington&#39;s       Parkinson&#39;s2       BA4   16.2   Sub Nigra   88.3       Huntington&#39;s2       Huntington&#39;s       BA4 PSP   0.0   Sub Nigra   28.9               Huntington&#39;s2       BA4 PSP2   55.1   Sub Nigra PSP2   2.3       BA4 Depression   24.1   Sub Nigra   0.0               Depression       BA4   8.9   Sub Nigra   8.8       Depression2       Depression2       BA7 Control   45.7   Glob Palladus   32.5               Control       BA7 Control2   52.9   Glob Palladus   6.2               Control2       BA7   12.5   Glob Palladus   29.3       Alzheimer&#39;s2       Alzheimer&#39;s       BA7 Parkinson&#39;s   31.9   Glob Palladus   11.4               Alzheimer&#39;s2       BA7   92.0   Glob Palladus   73.7       Parkinson&#39;s2       Parkinson&#39;s       BA7   41.2   Glob Palladus   60.7       Huntington&#39;s       Parkinson&#39;s2       BA7   68.3   Glob Palladus PSP   13.5       Huntington&#39;s2       BA7 PSP   36.9   Glob Palladus PSP2   22.2       BA7 PSP2   17.7   Glob Palladus   1.2               Depression       BA7 Depression   0.0   Temp Pole Control   35.4       BA9 Control   15.3   Temp Pole Control2   18.0       BA9 Control2   16.4   Temp Pole   0.0               Alzheimer&#39;s       BA9 Alzheimer&#39;s   19.2   Temp Pole   0.0               Alzheimer&#39;s2       BA9   9.5   Temp Pole   42.0       Alzheimer&#39;s2       Parkinson&#39;s       BA9 Parkinson&#39;s   46.7   Temp Pole   62.4               Parkinson&#39;s2       BA9   78.5   Temp Pole   65.5       Parkinson&#39;s2       Huntington&#39;s       BA9   65.5   Temp Pole PSP   0.0       Huntington&#39;s       BA9   13.4   Temp Pole PSP2   4.1       Huntington&#39;s2       BA9 PSP   17.1   Temp Pole   0.0               Depression2       BA9 PSP2   8.8   Cing Gyr Control   92.0       BA9 Depression   5.4   Cing Gyr Control2   44.4       BA9   37.4   Cing Gyr   11.3       Depression2       Alzheimer&#39;s       BA17 Control   31.4   Cing Gyr   10.5               Alzheimer&#39;s2       BA17 Control2   59.9   Cing Gyr   62.9               Parkinson&#39;s       BA17   19.9   Cing Gyr   40.6       Alzheimer&#39;s2       Parkinson&#39;s2       BA17   95.9   Cing Gyr   90.8       Parkinson&#39;s       Huntington&#39;s       BA17   100.0   Cing Gyr   40.3       Parkinson&#39;s2       Huntington&#39;s2       BA17   55.1   Cing Gyr PSP   12.0       Huntington&#39;s       BA17   43.8   Cing Gyr PSP2   0.0       Huntington&#39;s2       BA17   4.6   Cing Gyr Depression   17.6       Depression       BA17   12.0   Cing Gyr   42.6       Depression2       Depression2                    
     [0612]               TABLE HF                          general oncology screening panel_v_2.4                                 Rel. Exp.       Rel. Exp.           (%) Ag4100,       (%) Ag4100,           Run       Run       Tissue Name   268623631   Tissue Name   268623631                                     Colon cancer 1   42.3   Bladder cancer NAT 2   0.3       Colon NAT 1   11.1   Bladder cancer NAT 3   0.8       Colon cancer 2   10.2   Bladder cancer NAT 4   7.0       Colon cancer   7.1   Adenocarcinoma of the   12.4       NAT 2       prostate 1       Colon cancer 3   17.3   Adenocarcinoma of the   2.4               prostate 2       Colon cancer   9.7   Adenocarcinoma of the   13.0       NAT 3       prostate 3       Colon malignant   28.1   Adenocarcinoma of the   21.0       cancer 4       prostate 4       Colon normal   3.1   Prostate cancer NAT 5   6.1       adjacent tissue 4       Lung cancer 1   12.9   Adenocarcinoma of the   2.3               prostate 6       Lung NAT 1   0.2   Adenocarcinoma of the   3.4               prostate 7       Lung cancer 2   100.0   Adenocarcinoma of the   0.0               prostate 8       Lung NAT 2   3.0   Adenocarcinoma of the   17.3               prostate 9       Squamous cell   15.4   Prostate cancer NAT 10   0.9       carcinoma 3       Lung NAT 3   0.0   Kidney cancer 1   11.2       metastatic   12.3   KidneyNAT 1   1.9       melanoma 1       Melanoma 2   2.4   Kidney cancer 2   56.3       Melanoma 3   2.0   Kidney NAT 2   20.0       metastatic   26.4   Kidney cancer 3   24.7       melanoma 4       metastatic   18.9   Kidney NAT 3   13.1       melanoma 5       Bladder cancer 1   0.0   Kidney cancer 4   11.0       Bladder cancer   0.0   Kidney NAT 4   5.7       NAT 1       Bladder cancer 2   5.6                    
     [0613] CNS_neurodegeneration_v1.0 Summary: Ag4100 This panel does not show differential expression of the CG95775-01 gene in Alzheimer&#39;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.  
     [0614] General_screening_panel_v1.4 Summary: Ag4100 Highest expression of the CG95775-01 gene is seen in a breast cancer cell line (CT=26.9). This gene is widely expressed in this panel, with prominent levels of expression also seen in clusters of cell lines derived from breast cancer, ovarian cancer, melanoma, lung cancer, gastric cancer and brain cancer. Overall, this expression profile suggest that this gene product may be involved in cell proliferation and growth.  
     [0615] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, fetal liver 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.  
     [0616] 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&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0617] Panel 4.1D Summary: Ag4100 Highest expression of the CG95775-01 gene is seen in an untreated sample derived from the B cell line Ramos (CT=33). This gene is widely expressed at low but significant levels in many cells involved in the immune response including activated Th1, Th2 and Tr1 cells, CD8 and CD4 lymphocytes, activated PMBCs and B lymphocytes, LAK cells, eosinophils, and endothelial cells from lung and skin. This widespread 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.  
     [0618] Panel CNS — 1 Summary: Ag4100 This panel confirms expression of the CG95775-01 gene in in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.  
     [0619] general oncology screening panel_v — 2.4 Summary: Ag4100 Highest expression of the CG95775-01 gene is seen in lung cancer (OD06850-03C) sample (CT=29.2). Expression of this gene is higher in the cancer (OD06850-03C) sample as compared to control normal lung sample (CT=38). Thus, expression of this gene may be used to distinguish between these two samples. In addition, higher expression of this gene is also seen in other cancers such as lung, kidney, metastatic melanoma, bladder, and prostate cancer. Therefore, expression of this gene can be used as diagnostic marker for these cancers and also, therapeutic modulation of this gene product may be useful in the treatment of these cancers.  
     I. NOV23a (CG96221-01): Hydroxyproline-rich Glycoprotein  
     [0620] Expression of gene CG96221-01 was assessed using the primer-probe set Ag4042, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB, IC, ID and IE.  
               TABLE IA                          Probe Name Ag4042                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-agagagctgtttccaatatgca-3′   22   148   112               Probe   TET-5′-accattcaacacttccaactgtgtcg-3′-TAMRA   26   200   113               Reverse   5′-ctgaaggcctagttagccatgt-3′   22   226   114                  
 
     [0621]               TABLE IB                          CNS_neurodegeneration_v1.0                                 Rel. Exp.       Rel. Exp.           (%) Ag4042,       (%) Ag4042,           Run       Run       Tissue Name   214151951   Tissue Name   214151951                                     AD 1 Hippo   10.5   Control (Path) 3   3.7               Temporal Ctx       AD 2 Hippo   24.0   Control (Path) 4   32.3               Temporal Ctx       AD 3 Hippo   7.6   AD 1 Occipital Ctx   18.9       AD 4 Hippo   7.0   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   95.3   AD 3 Occipital Ctx   11.3       AD 6 Hippo   44.1   AD 4 Occipital Ctx   31.0       Control 2 Hippo   18.3   AD 5 Occipital Ctx   20.9       Control 4 Hippo   18.0   AD 6 Occipital Ctx   12.6       Control (Path) 3   8.0   Control 1 Occipital   5.0       Hippo       Ctx       AD 1 Temporal Ctx   27.9   Control 2 Occipital   19.9               Ctx       AD 2 Temporal Ctx   32.1   Control 3 Occipital   21.9               Ctx       AD 3 Temporal Ctx   11.5   Control 4 Occipital   13.7               Ctx       AD 4 Temporal Ctx   26.4   Control (Path) 1   100.0               Occipital Ctx       AD 5 Inf Temporal   69.3   Control (Path) 2       Ctx       Occipital Ctx       AD 5 Sup   57.8   Control (Path) 3   0.1       Temporal Ctx       Occipital Ctx       AD 6 Inf Temporal   40.6   Control (Path) 4   28.3       Ctx       Occipital Ctx       AD 6 Sup   43.2   Control 1 Parietal   16.7       Temporal Ctx       Ctx       Control 1 Temporal   4.2   Control 2 Parietal   51.4       Ctx       Ctx       Control 2 Temporal   22.8   Control 3 Parietal   23.7       Ctx       Ctx       Control 3 Temporal   13.8   Control (Path) 1   47.0       Ctx       Parietal Ctx       Control 3 Temporal   14.4   Control (Path) 2   26.8       Ctx       Parietal Ctx       Control (Path) 1   51.4   Control (Path) 3   5.1       Temporal Ctx       Parietal Ctx       Control (Path) 2   35.6   Control (Path) 4   40.6       Temporal Ctx       Parietal Ctx                    
     [0622]               TABLE IC                          General_screening_panel_v1.4                                 Rel. Exp.       Rel. Exp.           (%) Ag4042,       (%) Ag4042,           Run       Run       Tissue Name   218426120   Tissue Name   218426120                                     Adipose   0.3   Renal ca. TK-10   3.2       Melanoma*   0.1   Bladder   1.4       Hs688(A).T       Melanoma*   0.4   Gastric ca. (liver met.)   6.6       Hs688(B).T       NCI-N87       Melanoma* M14   0.6   Gastric ca. KATO III   5.0       Melanoma*   0.5   Colon ca. SW-948   0.9       LOXIMVI       Melanoma* SK-   2.5   Colon ca. SW480   13.4       MEL-5       Squamous cell   0.7   Colon ca.* (SW480   5.4       carcinoma SCC-4       met) SW620       Testis Pool   1.4   Colon ca. HT29   2.1       Prostate ca.* (bone   1.2   Colon ca. HCT-116   2.0       met) PC-3       Prostate Pool   1.1   Colon ca. CaCo-2   7.0       Placenta   0.3   Colon cancer tissue   1.8       Uterus Pool   0.4   Colon ca. SW1116   0.8       Ovarian ca.   1.0   Colon ca. Colo-205   1.2       OVCAR-3       Ovarian ca. SK-OV-   3.6   Colon ca. SW-48   0.6       3       Ovarian ca.   0.4   Colon Pool   3.8       OVCAR-4       Ovarian ca.   3.2   Small Intestine Pool   3.3       OVCAR-5       Ovarian ca.   3.2   Stomach Pool   1.1       IGROV-1       Ovarian ca.   0.4   Bone Marrow Pool   1.5       OVCAR-8       Ovary   1.4   Fetal Heart   4.8       Breast ca. MCF-7   100.0   Heart Pool   0.6       Breast ca. MDA-   0.5   Lymph Node Pool   4.3       MB-231       Breast ca. BT 549   3.3   Fetal Skeletal Muscle   2.3       Breast ca. T47D   6.7   Skeletal Muscle Pool   0.8       Breast ca.   1.5   Spleen Pool   1.2       MDA-N       Breast Pool   5.3   Thymus Pool   94.0       Trachea   0.7   CNS cancer (glio/   0.7               astro) U87-MG       Lung   0.7   CNS cancer (glio/   3.5               astro) U-118-MG       Fetal Lung   1.4   CNS cancer   1.7               (neuro;met) SK-N-AS       Lung ca. NCI-N417   0.2   CNS cancer (astro)   2.3               SF-539       Lung ca. LX-1   6.3   CNS cancer (astro)   8.0               SNB-75       Lung ca. NCI-H146   1.2   CNS cancer (glio)   2.2               SNB-19       Lung ca. SHP-77   0.6   CNS cancer (glio)   17.0               SF-295       Lung ca. A549   0.8   Brain (Amygdala)   0.3               Pool       Lung ca. NCI-H526   0.2   Brain (cerebellum)   1.7       Lung ca. NCI-H23   17.8   Brain (fetal)   2.0       Lung ca. NCI-H460   1.0   Brain (Hippocampus)   1.0               Pool       Lung ca. HOP-62   0.7   Cerebral Cortex Pool   1.7       Lung ca. NCI-H522   1.2   Brain (Substantia   1.1               nigra) Pool       Liver   0.1   Brain (Thalamus) Pool   1.8       Fetal Liver   2.4   Brain (whole)   0.5       Liver ca. HepG2   3.9   Spinal Cord Pool   1.8       Kidney Pool   3.8   Adrenal Gland   0.9       Fetal Kidney   5.0   Pituitary gland Pool   0.6       Renal ca. 786-0   2.2   Salivary Gland   0.2       Renal ca. A498   1.4   Thyroid (female)   96.6       Renal ca. ACHN   1.4   Pancreatic ca.   2.6               CAPAN2       Renal ca. UO-31   1.0   Pancreas Pool   3.2                    
     [0623]               TABLE ID                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4042, Run       Ag4042, Run       Tissue Name   171616938   Tissue Name   171616938                                     Secondary Th1 act   9.3   HUVEC IL-1beta   4.3       Secondary Th2 act   6.5   HUVEC IFN gamma   8.5       Secondary Tr1 act   9.9   HUVEC TNF alpha + IFN   4.9               gamma       Secondary Th1 rest   6.6   HUVEC TNF alpha + IL4   3.8       Secondary Th2 rest   3.1   HUVEC IL-11   1.6       Secondary Tr1 rest   2.8   Lung Microvascular EC   7.4               none       Primary Th1 act   0.6   Lung Microvascular EC   7.5               TNF alpha + IL-1beta       Primary Th2 act   12.4   Microvascular Dermal EC   3.3               none       Primary Tr1 act   8.8   Microsvasular Dermal EC   1.6               TNF alpha + IL-1beta       Primary Th1 rest   1.1   Bronchial epithelium   2.7               TNF alpha + IL1beta       Primary Th2 rest   0.8   Small airway epithelium   5.7               none       Primary Tr1 rest   3.4   Small airway epithelium   8.4               TNF alpha + IL-1beta       CD45RA CD4   7.0   Coronery artery SMC rest   1.5       lymphocyte act       CD45RO CD4   7.6   Coronery artery SMC   0.7       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   10.4   Astrocytes rest   3.5       Secondary CD8   2.8   Astrocytes TNF alpha +   2.2       lymphocyte rest       IL-1beta       Secondary CD8   3.6   KU-812 (Basophil) rest   65.1       lymphocyte act       CD4 lymphocyte none   4.4   KU-812 (Basophil)   94.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   11.9   CCD1106 (Keratinocytes)   13.3       CD95 CH11       none       LAK cells rest   9.5   CCD1106 (Keratinocytes)   6.6               TNF alpha + IL-1beta       LAK cells IL-2   8.7   Liver cirrhosis   0.2       LAK cells IL-2 + IL-12   2.5   NCI-H292 none   22.4       LAK cells IL-2 + IFN   9.2   NCI-H292 IL-4   8.5       gamma       LAK cells IL-2 + IL-18   14.8   NCI-H292 IL-9   27.2       LAK cells   0.9   NCI-H292 IL-13   10.9       PMA/ionomycin       NK Cells IL-2 rest   7.4   NCI-H292 IFN gamma   23.8       Two Way MLR 3 day   8.8   HPAEC none   2.8       Two Way MLR 5 day   5.8   HPAEC TNF alpha + IL-   3.5               1beta       Two Way MLR 7 day   8.3   Lung fibroblast none   9.2       PBMC rest   3.6   Lung fibroblast TNF alpha +   3.9               IL-1beta       PBMC PWM   10.2   Lung fibroblast IL-4   4.4       PBMC PHA-L   6.2   Lung fibroblast IL-9   3.0       Ramos (B cell) none   29.9   Lung fibroblast IL-13   4.5       Ramos (B cell)   33.7   Lung fibroblast IFN   3.5       ionomycin       gamma       B lymphocytes PWM   3.4   Dermal fibroblast   9.0               CCD1070 rest       B lymphocytes CD40L   11.4   Dermal fibroblast   20.4       and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast   3.6               CCD1070 IL-1beta       EOL-1 dbcAMP   0.0   Dermal fibroblast IFN   1.6       PMA/ionomycin       gamma       Dendritic cells none   3.2   Dermal fibroblast IL-4   8.5       Dendritic cells LPS   6.7   Dermal Fibroblasts rest   6.3       Dendritic cells anti-   9.7   Neutrophils TNFa + LPS   1.5       CD40       Monocytes rest   2.3   Neutrophils rest   2.5       Monocytes LPS   3.5   Colon   8.3       Macrophages rest   8.8   Lung   3.5       Macrophages LPS   0.8   Thymus   21.2       HUVEC none   0.0   Kidney   100.0       HUVEC starved   1.8                    
     [0624]               TABLE IE                          general oncology screening panel_v_2.4                                 Rel. Exp. (%) Ag4042,       Rel. Exp. (%) Ag4042,       Tissue Name   Run 268362930   Tissue Name   Run 268362930                                     Colon cancer 1   10.7   Bladder cancer NAT 2   0.0       Colon cancer NAT 1   1.7   Bladder cancer NAT 3   0.4       Colon cancer 2   2.0   Bladder cancer NAT 4   1.5       Colon cancer NAT 2   0.4   Adenocarcinoma of the   34.6               prostate 1       Colon cancer 3   100.0   Adenocarcinoma of the   4.0               prostate 2       Colon cancer NAT 3   4.5   Adenocarcinoma of the   5.2               prostate 3       Colon malignant   17.1   Adenocarcinoma of the   41.8       cancer 4       prostate 4       Colon normal   4.1   Prostate cancer NAT 5   4.5       adjacent tissue 4       Lung cancer 1   20.7   Adenocarcinoma of the   4.0               prostate 6       Lung NAT 1   0.7   Adenocarcinoma of the   4.2               prostate 7       Lung cancer 2   30.1   Adenocarcinoma of the   2.7               prostate 8       Lung NAT 2   3.2   Adenocarcinoma of the   12.1               prostate 9       Squamous cell   8.4   Prostate cancer NAT 10   0.9       carcinoma 3       Lung NAT 3   1.1   Kidney cancer 1   18.3       metastatic   5.7   KidneyNAT 1   5.7       melanoma 1       Melanoma 2   3.3   Kidney cancer 2   80.7       Melanoma 3   0.6   Kidney NAT 2   21.3       metastatic   36.6   Kidney cancer 3   15.5       melanoma 4       metastatic   21.3   Kidney NAT 3   2.1       melanoma 5       Bladder cancer 1   0.7   Kidney cancer 4   1.5       Bladder cancer   0.0   Kidney NAT 4   0.9       NAT 1       Bladder cancer 2   1.7                    
     [0625] CNS_neurodegeneration_v1.0 Summary: Ag4042 This panel does not show differential expression of the CG96221-01 gene in Alzheimer&#39;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.  
     [0626] General_screening_panel v1.4 Summary: Ag4042 Highest expression of the CG96221-01 gene is seen in a breast cancer cell line (CT=25.9), with high levels of expression also seen in the thyroid and thymus. Thus, expression of this gene could be used to distinguish these samples from other samples on this panel and as a marker of breast cancer and thyroid and thymic tissue. Furthermore, therapeutic modulation of the expression or function of this gene may be of use in the treatment of breast cancer and the thyroidopathies.  
     [0627] Overall, this gene is ubiquitously expressed with moderate to low levels of expression seen in other metabolic tissues including in pituitary, adipose, adrenal gland, pancreas, fetal liver 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.  
     [0628] In addition, this gene is expressed at much higher levels in fetal liver (CT=31.3) when compared to expression in the adult counterpart (CT=36.3). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.  
     [0629] 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&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy  
     [0630] Panel 4.1D Summary: Ag4042 Highest expression of the CG96221-01 gene is seen in the kidney (CT=30.2), with low but significant expression in the thymus. The expression of this gene is widespread throughout this panel with prominent expression also detected in both treated and untreated basophils. Basophils release histamines and other biological modifiers in reponse to allergens and play an important role in the pathology of asthma and hypersensitivity reactions. Therefore, therapeutics designed against the putative protein encoded by this gene may reduce or inhibit inflammation by blocking basophil function in these diseases. In addition, these cells are a reasonable model for the inflammatory cells that take part in various inflammatory lung and bowel diseases, such as asthma, Crohn&#39;s disease, and ulcerative colitis. Therefore, therapeutics that modulate the function of this gene product may reduce or eliminate the symptoms of patients suffering from asthma, Crohn&#39;s disease, and ulcerative colitis.  
     [0631] general oncology screening panel_v — 2.4 Summary: Ag4042 Highest expression of the CG96221-01 gene is seen in colon cancer (CT=29), with significant expression also seen in prostate and kidney cancer. In addition, expression of this gene is higher in the cancers than in the normal adjacent tissue. Therefore, expression of this gene could be as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, kidney and prostate cancer.  
     J. NOV25a (CG96394-01): HIC1  
     [0632] Expression of gene CG96394-01 was assessed using the primer-probe set Ag4054, described in Table JA. Results of the RTQ-PCR runs are shown in Tables JB, JC, JD and JE.  
               TABLE JA                          Probe Name Ag4054                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-gtcatcatcatggtggagaact-3′   22   226   115               Probe   TET-5′-cacaagaacgtcctagccgccag-3′-TAMRA   23   262   116               Reverse   5′-aggaccagggacttgaaataga-3′   22   290   117                  
 
     [0633]               TABLE JB                          General_screening_panel_v1.4                                 Rel. Exp. (%) Ag4054,       Rel. Exp. (%) Ag4054,       Tissue Name   Run 218713208   Tissue Name   Run 218713208                                     Adipose   4.1   Renal ca. TK-10   18.0       Melanoma*   3.2   Bladder   6.7       Hs688(A).T       Melanoma*   1.6   Gastric ca. (liver met.)   17.3       Hs688(B).T       NCI-N87       Melanoma* M14   13.1   Gastric ca. KATO III   18.3       Melanoma*   4.1   Colon ca. SW-948   2.7       LOXIMVI       Melanoma* SK-   8.4   Colon ca. SW480   8.0       MEL-5       Squamous cell   10.3   Colon ca.* (SW480   9.0       carcinoma SCC-4       met) SW620       Testis Pool   7.6   Colon ca. HT29   3.7       Prostate ca.* (bone   4.4   Colon ca. HCT-116   20.7       met) PC-3       Prostate Pool   2.0   Colon ca. CaCo-2   100.0       Placenta   28.9   Colon cancer tissue   6.0       Uterus Pool   1.2   Colon ca. SW1116   3.3       Ovarian ca.   17.9   Colon ca. Colo-205   3.1       OVCAR-3       Ovarian ca. SK-OV-3   15.2   Colon ca. SW-48   2.2       Ovarian ca.   5.0   Colon Pool   5.2       OVCAR-4       Ovarian ca.   10.7   Small Intestine Pool   8.4       OVCAR-5       Ovarian ca. IGROV-1   7.4   Stomach Pool   3.1       Ovarian ca.   3.8   Bone Marrow Pool   1.9       OVCAR-8       Ovary   6.6   Fetal Heart   4.9       Breast ca. MCF-7   4.9   Heart Pool   1.9       Breast ca. MDA-   4.5   Lymph Node Pool   5.5       MB-231       Breast ca. BT 549   13.1   Fetal Skeletal Muscle   2.3       Breast ca. T47D   21.5   Skeletal Muscle Pool   3.5       Breast ca. MDA-N   3.0   Spleen Pool   4.2       Breast Pool   5.4   Thymus Pool   11.3       Trachea   3.3   CNS cancer (glio/astro)   8.1               U87-MG       Lung   1.2   CNS cancer (glio/astro)   17.3               U-118-MG       Fetal Lung   13.5   CNS cancer   21.6               (neuro;met) SK-N-AS       Lung ca. NCI-N417   2.3   CNS cancer (astro) SF-   3.7               539       Lung ca. LX-1   8.0   CNS cancer (astro)   10.7               SNB-75       Lung ca. NCI-H146   7.2   CNS cancer (glio)   9.4               SNB-19       Lung ca. SHP-77   9.1   CNS cancer (glio) SF-   13.2               295       Lung ca. A549   7.0   Brain (Amygdala) Pool   3.1       Lung ca. NCI-H526   5.6   Brain (cerebellum)   7.7       Lung ca. NCI-H23   10.8   Brain (fetal)   30.4       Lung ca. NCI-H460   3.6   Brain (Hippocampus)   2.6               Pool       Lung ca. HOP-62   5.9   Cerebral Cortex Pool   4.5       Lung ca. NCI-H522   11.0   Brain (Substantia nigra)   3.3               Pool       Liver   0.5   Brain (Thalamus) Pool   4.4       Fetal Liver   31.9   Brain (whole)   8.0       Liver ca. HepG2   23.8   Spinal Cord Pool   3.8       Kidney Pool   10.7   Adrenal Gland   3.8       Fetal Kidney   10.4   Pituitary gland Pool   1.6       Renal ca. 786-0   8.4   Salivary Gland   1.4       Renal ca. A498   1.8   Thyroid (female)   3.7       Renal ca. ACHN   4.7   Pancreatic ca.   4.6               CAPAN2       Renal ca. UO-31   4.5   Pancreas Pool   6.9                    
     [0634]               TABLE JC                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4054, Run       Ag4054, Run       Tissue Name   171619967   Tissue Name   171619967                                     Secondary Th1 act   44.8   HUVEC IL-1beta   23.2       Secondary Th2 act   51.8   HUVEC IFN gamma   17.9       Secondary Tr1 act   37.1   HUVEC TNF alpha + IFN   17.3               gamma       Secondary Th1 rest   12.4   HUVEC TNF alpha + IL4   22.1       Secondary Th2 rest   11.7   HUVEC IL-11   17.8       Secondary Tr1 rest   12.6   Lung Microvascular EC   27.4               none       Primary Th1 act   58.2   Lung Microvascular EC   29.9               TNF alpha + IL-1beta       Primary Th2 act   49.0   Microvascular Dermal EC   21.8               none       Primary Tr1 act   52.5   Microsvasular Dermal EC   15.5               TNF alpha + IL-1beta       Primary Th1 rest   12.7   Bronchial epithelium   5.7               TNF alpha + IL1beta       Primary Th2 rest   7.8   Small airway epithelium   10.7               none       Primary Tr1 rest   19.9   Small airway epithelium   24.7               TNF alpha + IL-1beta       CD45RA CD4   22.4   Coronery artery SMC rest   16.8       lymphocyte act       CD45RO CD4   33.4   Coronery artery SMC   11.6       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   24.5   Astrocytes rest   11.4       Secondary CD8   18.9   Astrocytes TNF alpha +   4.2       lymphocyte rest       IL-1beta       Secondary CD8   15.4   KU-812 (Basophil) rest   44.4       lymphocyte act       CD4 lymphocyte none   16.7   KU-812 (Basophil)   42.3               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   14.6   CCD1106 (Keratinocytes)   81.2       CD95 CH11       none       LAK cells rest   30.8   CCD1106 (Keratinocytes)   53.2               TNF alpha + IL-1beta       LAK cells IL-2   12.2   Liver cirrhosis   9.5       LAK cells IL-2 + IL-12   11.3   NCI-H292 none   10.0       LAK cells IL-2 + IFN   11.1   NCI-H292 IL-4   14.5       gamma       LAK cells IL-2 + IL-18   5.8   NCI-H292 IL-9   11.0       LAK cells   81.8   NCI-H292 IL-13   14.9       PMA/ionomycin       NK Cells IL-2 rest   35.6   NCI-H292 IFN gamma   12.3       Two way MLR 3 day   36.6   HPAEC none   11.3       Two Way MLR 5 day   41.8   HPAEC TNF alpha + IL-   21.6               1beta       Two Way MLR 7 day   32.8   Lung fibroblast none   23.0       PBMC rest   24.1   Lung fibroblast TNF alpha +   19.1               IL-1beta       PBMC PWM   47.6   Lung fibroblast IL-4   15.1       PBMC PHA-L   36.6   Lung fibroblast IL-9   34.6       Ramos (B cell) none   68.8   Lung fibroblast IL-13   21.9       Ramos (B cell)   92.7   Lung fibroblast IFN   24.8       ionomycin       gamma       B lymphocytes PWM   27.9   Dermal fibroblast   23.3               CCD1070 rest       B lymphocytes CD40L   34.9   Dermal fibroblast   35.4       and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   57.4   Dermal fibroblast   22.5               CCD1070 IL-1beta       EOL-1 dbcAMP   32.8   Dermal fibroblast IFN   18.6       PMA/ionomycin       gamma       Dendritic cells none   46.3   Dermal fibroblast IL-4   25.9       Dendritic cells LPS   45.7   Dermal Fibroblasts rest   11.7       Dendritic cells anti-   42.9   Neutrophils TNFa + LPS   7.3       CD40       Monocytes rest   55.9   Neutrophils rest   13.9       Monocytes LPS   54.3   Colon   11.0       Macrophages rest   100.0   Lung   12.2       Macrophages LPS   30.6   Thymus   66.4       HUVEC none   21.0   Kidney   66.4       HUVEC starved   27.0                    
     [0635]               TABLE JD                          Panel 5 Islet                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4054, Run       Ag4054, Run       Tissue Name   263594788   Tissue Name   263594788                                     97457_Patient-   10.4   94709_Donor 2 AM - A_adipose   16.2       02go_adipose       97476_Patient-   2.7   94710_Donor 2 AM - B_adipose   3.0       07sk_skeletal muscle       97477_Patient-   2.7   94711_Donor 2 AM - C_adipose   4.2       07ut_uterus       97478_Patient-   61.6   94712_Donor 2 AD - A_adipose   4.8       07pl_placenta       99167_Bayer Patient 1   47.6   94713_Donor 2 AD - B_adipose   11.9       97482_Patient-   7.3   94714_Donor 2 AD - C_adipose   7.1       08ut_uterus       97483_Patient-   16.8   94742_Donor 3 U -    4.5       08pl_placenta       A_Mesenchymal Stem Cells       97486_Patient-   1.9   94743_Donor 3 U -    3.1       09sk_skeletal muscle       B_Mesenchymal Stem Cells       97487_Patient-   4.0   94730_Donor 3 AM - A_adipose   7.4       09ut_uterus       97488_Patient-   31.0   94731_Donor 3 AM - B_adipose   1.3       09pl_placenta       97492_Patient-   5.3   94732_Donor 3 AM - C_adipose   8.2       10ut_uterus       97493_Patient-   100.0   94733_Donor AD - A_Aadiose   10.0       10pl_placenta       97495_Patient-   6.5   94734_Donor 3 AD - B_adipose   3.2       11go_adipose       97496_Patient-   9.2   94735_Donor 3 AD - C_adipose   4.0       11sk_skeletal muscle       97497_Patient-   6.1   77138_Liver_HepG2untreated   74.2       11ut_uterus       97498_Patient-   39.8   73556_Heart_Cardiac stromal   9.3       11pl_placenta       cells (primary)       97500_Patient-   18.6   81735_Small Intestine   5.8       12go_adipose       97501_Patient-   26.6   72409_Kidney_Proximal   2.3       12sk_skeletal muscle       Convoluted Tubule       97502_Patient-   0.8   82685_Small intestine_Duodenum   4.0       12ut_uterus       97503_Patient-   19.8   90650_Adrenal_Adrenocortical   1.8       12pl_placenta       adenoma       94721_Donor 2 U -   3.1   72410_Kidney_HRCE   11.6       A_Mesenchymal Stem       Cells       94722_Donor 2 U -   5.5   72411_Kidney_HRE   5.5       B_Mesenchymal Stem       Cells       94723_Donor 2 U -   4.6   73139_Uterus_Uterine smooth   5.8       C_Mesenchymal Stem       muscle cells       Cells                    
     [0636]               TABLE JE                          general oncology screening panel_v_2.4                                 Rel. Exp. (%) Ag4054,       Rel. Exp. (%) Ag4054,       Tissue Name   Run 268362958   Tissue Name   Run 268362958                                     Colon cancer 1   15.4   Bladder cancer NAT 2   0.2       Colon cancer NAT 1   2.8   Bladder cancer NAT 3   0.2       Colon cancer 2   6.1   Bladder cancer NAT 4   2.7       Colon cancer NAT 2   3.1   Adenocarcinoma of the   8.8               prostate 1       Colon cancer 3   10.8   Adenocarcinoma of the   1.3               prostate 2       Colon cancer NAT 3   8.3   Adenocarcinoma of the   3.3               prostate 3       Colon malignant   26.1   Adenocarcinoma of the   11.9       cancer 4       prostate 4       Colon normal   2.3   Prostate cancer NAT 5   1.8       adjacent tissue 4       Lung cancer 1   12.8   Adenocarcinoma of the   2.9               prostate 6       Lung NAT 1   1.9   Adenocarcinoma of the   3.5               prostate 7       Lung cancer 2   100.0   Adenocarcinoma of the   1.3               prostate 8       Lung NAT 2   5.2   Adenocarcinoma of the   5.0               prostate 9       Squamous cell   16.8   Prostate cancer NAT 10   0.9       carcinoma 3       Lung NAT 3   1.3   Kidney cancer 1   17.3       metastatic   14.1   KidneyNAT 1   9.4       melanoma 1       Melanoma 2   5.2   Kidney cancer 2   26.2       Melanoma 3   1.7   Kidney NAT 2   13.0       metastatic   29.7   Kidney cancer 3   31.2       melanoma 4       metastatic   29.9   Kidney NAT 3   6.6       melanoma 5       Bladder cancer 1   1.2   Kidney cancer 4   14.3       Bladder cancer   0.0   Kidney NAT 4   5.1       NAT 1       Bladder cancer 2   3.3                    
     [0637] General_screening_panel_v1.4 Summary: Ag4054 Highest expression of the CG96394-01 gene is seen in a colon cancer cell line (CT=26.5). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of breast cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of breast cancer.  
     [0638] 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.  
     [0639] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0640] Panel 4.1D Summary: Ag4054 Highest expression of the CG96394-01 gene is seen in resting macrophages (CT=30.). In addition, moderate to low levels of expression of this gene are seen in many samples on this panel including 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.  
     [0641] Panel 5 Islet Summary: Ag4054 Highest expression of the CG96394-01 gene is seen in placenta (CT=29.4). In addition, expression in this panel confirms expression of this gene in tissues with metabolic function. Please see Panel 1.4 for discussion of this gene in metabolic disease.  
     [0642] general oncology screening_panel_v — 2.4 Summary: Ag4054 Highest expression of the CG96394-01 gene is seen in a colon cancer (CT=28.3), consistent with expression in Panel 1.4. In addition, expression is higher in colon, kidney and lung cancers when compred to expression in normal adjacent tissue. 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 colon, kidney and lung cancer.  
     K. NOV27a (CG96650-01): Hypothetical Benzodiazepine Receptor Related Protein  
     [0643] Expression of gene C696650-01 was assessed using the primer-probe set Ag4341, described in Table KA. Results of the RTQ-PCR runs are shown in Tables KB and KC.  
               TABLE KA                          Probe Name Ag4341                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-aatgacccacaggaggctag-3′   20   60   118               Probe   TET-5′-caattgtctagtggctgtggggtgg-3′-TAMRA   25   82   119               Reverse   5′-cttcttccttcaccccatgt-3′   20   136   120                  
 
     [0644]               TABLE KB                          General_screening_panel_v1.4                                 Rel. Exp. (%) Ag4341,       Rel. Exp. (%) Ag4341,       Tissue Name   Run 220361706   Tissue Name   Run 220361706                                     Adipose   0.0   Renal ca. TK-10   6.7       Melanoma*   1.7   Bladder   3.1       Hs688(A).T       Melanoma*   0.0   Gastric ca. (liver met.)   9.7       Hs688(B).T       NCI-N87       Melanoma* M14   15.0   Gastric ca. KATO III   92.0       Melanoma*   13.8   Colon ca. SW-948   8.5       LOXIMVI       Melanoma* SK-   5.3   Colon ca. SW480   100.0       MEL-5       Squamous cell   30.6   Colon ca.* (SW480   33.7       carcinoma SCC-4       met) SW620       Testis Pool   3.8   Colon ca. HT29   6.0       Prostate ca.* (bone   3.9   Colon ca. HCT-116   36.9       met) PC-3       Prostate Pool   0.0   Colon ca. CaCo-2   16.4       Placenta   3.1   Colon cancer tissue   0.0       Uterus Pool   0.0   Colon ca. SW1116   9.5       Ovarian ca.   17.0   Colon ca. Colo-205   3.0       OVCAR-3       Ovarian ca. SK-OV-3   18.2   Colon ca. SW-48   0.9       Ovarian ca.   4.1   Colon Pool   0.4       OVCAR-4       Ovarian ca.   7.1   Small Intestine Pool   1.3       OVCAR-5       Ovarian ca. IGROV-1   1.7   Stomach Pool   0.0       Ovarian ca.   1.6   Bone Marrow Pool   0.6       OVCAR-8       Ovary   0.0   Fetal Heart   7.6       Breast ca. MCF-7   2.6   Heart Pool   0.0       Breast ca. MDA-   35.1   Lymph Node Pool   1.2       MB-231       Breast ca. BT 549   40.9   Fetal Skeletal Muscle   4.9       Breast ca. T47D   3.1   Skeletal Muscle Pool   0.0       Breast ca. MDA-N   6.1   Spleen Pool   0.0       Breast Pool   0.0   Thymus Pool   0.9       Trachea   0.0   CNS cancer (glio/astro)   11.3               U87-MG       Lung   0.0   CNS cancer (glio/astro)   57.4               U-118-MG       Fetal Lung   5.0   CNS cancer   39.0               (neuro;met) SK-N-AS       Lung ca. NCI-N417   7.3   CNS cancer (astro) SF-   4.8               539       Lung ca. LX-1   30.6   CNS cancer (astro)   10.2               SNB-75       Lung ca. NCI-H146   7.9   CNS cancer (glio)   0.0               SNB-19       Lung ca. SHP-77   6.6   CNS cancer (glio) SF-   0.0               295       Lung ca. A549   24.3   Brain (Amygdala) Pool   0.0       Lung ca. NCI-H526   6.6   Brain (cerebellum)   6.0       Lung ca. NCI-H23   19.8   Brain (fetal)   4.6       Lung ca. NCI-H460   0.0   Brain (Hippocampus)   0.0               Pool       Lung ca. HOP-62   2.1   Cerebral Cortex Pool   2.1       Lung ca. NCI-H522   19.1   Brain (Substantia nigra)   0.0               Pool       Liver   0.0   Brain (Thalamus) Pool   0.0       Fetal Liver   17.0   Brain (whole)   1.2       Liver ca. HepG2   1.2   Spinal Cord Pool   0.0       Kidney Pool   0.0   Adrenal Gland   0.0       Fetal Kidney   2.4   Pituitary gland Pool   0.0       Renal ca. 786-0   10.1   Salivary Gland   0.0       Renal ca. A498   1.6   Thyroid (female)   0.0       Renal ca. ACHN   1.3   Pancreatic ca.   25.9               CAPAN2       Renal ca. UO-31   2.1   Pancreas Pool   3.2                    
     [0645]               TABLE KC                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4341, Run       Ag4341, Run       Tissue Name   183719667   Tissue Name   183719667                                     Secondary Th1 act   47.0   HUVEC IL-1beta   8.9       Secondary Th2 act   82.4   HUVEC IFN gamma   14.5       Secondary Tr1 act   94.0   HUVEC TNF alpha + IFN   4.3               gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha + IL4   16.7       Secondary Th2 rest   9.1   HUVEC IL-11   4.0       Secondary Tr1 rest   0.0   Lung Microvascular EC   8.0               none       Primary Th1 act   23.7   Lung Microvascular EC   3.6               TNF alpha + IL-1beta       Primary Th2 act   70.7   Microvascular Dermal EC   18.2               none       Primary Tr1 act   40.1   Microvascular Dermal EC   4.8               TNF alpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   0.0               TNF alpha + IL1beta       Primary Th2 rest   11.7   Small airway epithelium   6.7               none       Primary Tr1 rest   24.0   Small airway epithelium   3.7               TNF alpha + IL-1beta       CD45RA CD4   10.4   Coronery artery SMC rest   9.9       lymphocyte act       CD45RO CD4   57.8   Coronery artery SMC   0.0       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   43.8   Astrocytes rest   0.0       Secondary CD8   5.6   Astrocytes TNF alpha +   0.0       lymphocyte rest       IL-1beta       Secondary CD8   21.5   KU-812 (Basophil) rest   38.7       lymphocyte act       CD4 lymphocyte none   0.0   KU-812 (Basophil)   45.4               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   16.7   CCD1106 (Keratinocytes)   42.9       CD95 CH11       none       LAK cells rest   3.2   CCD1106 (Keratinocytes)   13.6               TNF alpha + IL-1beta       LAK cells IL-2   8.0   Liver cirrhosis   0.0       LAK cells IL-2 + IL-12   10.9   NCI-H292 none   3.9       LAK cells IL-2 + IFN   22.5   NCI-H292 IL-4   70.2       gamma       LAK cells IL-2 + IL-18   8.6   NCI-H292 IL-9   49.0       LAK cells   13.5   NCI-H292 IL-13   100.0       PMA/ionomycin       NK Cells IL-2 rest   38.2   NCI-H292 IFN gamma   21.5       Two Way MLR 3 day   0.0   HPAEC none   19.3       Two Way MLR 5 day   18.8   HPAEC TNF alpha + IL-   17.4               1beta       Two Way MLR 7 day   3.9   Lung fibroblast none   5.6       PBMC rest   0.0   Lung fibroblast TNF alpha +   20.6               IL-1beta       PBMC PWM   22.1   Lung fibroblast IL-4   0.0       PBMC PHA-L   35.1   Lung fibroblast IL-9   21.9       Ramos (B cell) none   37.9   Lung fibroblast IL-13   0.0       Ramos (B cell)   67.4   Lung fibroblast IFN   0.0       ionomycin       gamma       B lymphocytes PWM   33.0   Dermal fibroblast   43.2               CCD1070 rest       B lymphocytes CD40L   15.5   Dermal fibroblast   50.7       and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   30.1   Dermal fibroblast   51.4               CCD1070 IL-1beta       EOL-1 dbcAMP   18.2   Dermal fibroblast IFN   0.0       PMA/ionomycin       gamma       Dendritic cells none   0.0   Dermal fibroblast IL-4   19.6       Dendritic cells LPS   0.0   Dermal Fibroblasts rest   4.7       Dendritic cells anti-   0.0   Neutrophils TNFa + LPS   11.0       CD40       Monocytes rest   0.0   Neutrophils rest   0.0       Monocytes LPS   0.0   Colon   0.0       Macrophages rest   0.0   Lung   15.4       Macrophages LPS   0.0   Thymus   10.4       HUVEC none   18.2   Kidney   18.8       HUVEC starved   11.0                    
     [0646] General_screening_panel_v1.4 Summary: Ag4341 Expression of the CG96650-01 gene is highest in a colon cancer cell line, SW480 (CT=31.7). Expression is downregulated in the colon cancer cell line SW690 which is derived from a metastasis of the SW480 derived sample. Thus, expression of this gene may be able to differentiate between these two cell lines and between primary and metastatic colon tumors. Overall, expression of this gene is limited to samples derived from cancer cell lines, with expression in cell lines derived from pancreatic, brain, colon, lung, breast, ovarian and melanoma cancers. Thus, expression of this gene could also be used as a diagnostic marker for the presence of cancer. Modulation of the expression or function of this gene or gene product may also be useful in the treatment of cancer.  
     [0647] Panel 4.1D Summary: Ag4341 Expression of the CG96650-01 gene is highest in IL-13 treated NCI-H292 cells (CT=32.9). Low but significant levels of expression are also evident in other sampels on this panel including dermal fibroblasts, NCI-H292 cells, basophils, B cells, and chronically activated T cells. Thus, this gene may be involved in autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     L. NOV30a (CG97090-01) and NOV30b (CG97090-02): FIP-2  
     [0648] Expression of gene CG97090-01 and variant CG97090-02 was assessed using the primer-probe set Ag6162, described in Table LA.  
               TABLE LA                          Probe Name Ag6162                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ttgtgtgtcatctgtagcacagtta-3′   25   1139   121               Probe   TET-5′-tggacttttcatcctctgttttagcc-3′-TAMRA   26   1110   122               Reverse   5′-gctatcagaaatcaaaatggaaca-3′   24   1086   123                  
 
     [0649]               TABLE MA                          Probe Name Ag1970                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tgcagttgaagagctacatacg-3′   22   2046   124               Probe   TET-5′-cagacgttaacaaattcctttacccaagg-3′-TAMRA   29   2088   125               Reverse   5′-aagtaaactgcggaaaggtcat-3′   22   2124   126                    
     [0650]               TABLE MB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%) Ag1970,       Rel. Exp. (%) Ag1970,       Tissue Name   Run 207794532   Tissue Name   Run 207794532                                     AD 1 Hippo   25.3   Control (Path) 3   17.8               Temporal Ctx       AD 2 Hippo   26.2   Control (Path) 4   40.1               Temporal Ctx       AD 3 Hippo   10.4   AD 1 Occipital Ctx   14.8       AD 4 Hippo   5.4   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   92.7   AD 3 Occipital Ctx   28.3       AD 6 Hippo   29.1   AD 4 Occipital Ctx   33.4       Control 2 Hippo   49.0   AD 5 Occipital Ctx   61.1       Control 4 Hippo   1.8   AD 6 Occipital Ctx   24.3       Control (Path) 3   17.9   Control 1 Occipital   11.7       Hippo       Ctx       AD 1 Temporal Ctx   22.2   Control 2 Occipital   73.2               Ctx       AD 2 Temporal Ctx   47.0   Control 3 Occipital   25.9               Ctx       AD 3 Temporal Ctx   6.2   Control 4 Occipital   19.8               Ctx       AD 4 Temporal Ctx   34.9   Control (Path) 1   49.7               Occipital Ctx       AD 5 Inf Temporal   100.0   Control (Path) 2   23.7       Ctx       Occipital Ctx       AD 5 Sup   81.2   Control (Path) 3   14.9       Temporal Ctx       Occipital Ctx       AD 6 Inf Temporal   37.6   Control (Path) 4   24.5       Ctx       Occipital Ctx       AD 6 Sup   11.6   Control 1 Parietal   17.6       Temporal Ctx       Ctx       Control 1 Temporal   19.1   Control 2 Parietal   73.7       Ctx       Ctx       Control 2 Temporal   47.0   Control 3 Parietal   38.7       Ctx       Ctx       Control 3 Temporal   33.9   Control (Path) 1   67.4       Ctx       Parietal Ctx       Control 3 Temporal   28.9   Control (Path) 2   38.2       Ctx       Parietal Ctx       Control (Path) 1   50.7   Control (Path) 3   13.9       Temporal Ctx       Parietal Ctx       Control (Path) 2   29.7   Control (Path) 4   46.3       Temporal Ctx       Parietal Ctx                    
     [0651]               TABLE MC                          Panel 1.3D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag1970, Run       Ag1970, Run       Tissue Name   165544918   Tissue Name   165544918                                     Liver adenocarcinoma   0.1   Kidney (fetal)   0.0       Pancreas   0.1   Renal ca. 786-0   0.0       Pancreatic ca. CAPAN 2   0.0   Renal ca. A498   0.0       Adrenal gland   0.1   Renal ca. RXF 393   0.0       Thyroid   0.0   Renal ca. ACHN   0.0       Salivary gland   0.1   Renal ca. UO-31   0.0       Pituitary gland   0.0   Renal ca. TK-10   0.0       Brain (fetal)   10.1   Liver   0.0       Brain (whole)   47.0   Liver (fetal)   0.0       Brain (amygdala)   57.0   Liver ca.   0.0               (hepatoblast) HepG2       Brain (cerebellum)   12.7   Lung   0.1       Brain (hippocampus)   100.0   Lung (fetal)   0.3       Brain (substantia nigra)   100.0   Lung ca. (small cell)   0.0               LX-1       Brain (thalamus)   93.3   Lung ca. (small cell)   0.0               NCI-H69       Cerebral Cortex   17.0   Lung ca. (s.cell var.)   0.0               SHP-77       Spinal cord   37.4   Lung ca. (large   0.1               cell)NCI-H460       glio/astro U87-MG   0.0   Lung ca. (non-sm.   0.0               cell) A549       glio/astro U-118-MG   0.0   Lung ca. (non-s.cell)   0.0               NCI-H23       astrocytoma SW1783   0.0   Lung ca. (non-s.cell)   0.0               HOP-62       neuro*; met SK-N-AS   0.0   Lung ca. (non-s.cl)   0.1               NCI-H522       astrocytoma SF-539   0.0   Lung ca. (squam.)   0.0               SW 900       astrocytoma SNB-75   0.0   Lung ca. (squam.)   0.0               NCI-H596       glioma SNB-19   3.6   Mammary gland   0.6       glioma U251   0.0   Breast ca.* (pl.ef)   0.0               MCF-7       glioma SF-295   0.0   Breast ca.* (pl.ef) MDA-MB-   0.0               231       Heart (fetal)   0.0   Breast ca.* (pl.ef) T47D   0.0       Heart   0.0   Breast ca. BT-549   0.0       Skeletal muscle (fetal)   0.0   Breast ca. MDA-N   0.1       Skeletal muscle   0.2   Ovary   0.0       Bone marrow   0.1   Ovarian ca.   0.1               OVCAR-3       Thymus   0.1   Ovarian ca.   0.0               OVCAR-4       Spleen   0.5   Ovarian ca.   0.0               OVCAR-5       Lymph node   0.1   Ovarian ca.   0.0               OVCAR-8       Colorectal   0.0   Ovarian ca. IGROV-1   0.0       Stomach   0.0   Ovarian ca.*   0.0               (ascites) SK-OV-3       Small intestine   0.1   Uterus   0.0       Colon ca. SW480   0.1   Placenta   0.1       Colon ca.*   0.0   Prostate   0.0       SW620(SW480 met)       Colon ca. HT29   0.0   Prostate ca.* (bone   0.0               met)PC-3       Colon ca. HCT-116   0.0   Testis   0.7       Colon ca. CaCo-2   0.0   Melanoma   0.0               Hs688(A).T       Colon ca.   0.0   Melanoma* (met)   0.0       tissue(ODO3866)       Hs688(B).T       Colon ca. HCC-2998   0.0   Melanoma UACC-   0.0               62       Gastric ca.* (liver met)   0.0   Melanoma M14   0.6       NCI-N87       Bladder   0.0   Melanoma LOX   0.0               IMVI       Trachea   0.0   Melanoma* (met)   0.1               SK-MEL-5       Kidney   0.3   Adipose   0.1                    
     [0652]               TABLE MD                          Panel 4D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag1970, Run       Ag1970, Run       Tissue Name   159624930   Tissue Name   159624930                                     Secondary Th1 act   0.0   HUVEC IL-1beta   0.0       Secondary Th2 act   0.0   HUVEC IFN gamma   0.0       Secondary Tr1 act   0.0   HUVEC TNF alpha + IFN   0.0               gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha + IL4   0.0       Secondary Th2 rest   0.0   HUVEC IL-11   0.0       Secondary Tr1 rest   0.0   Lung Microvascular EC   0.0               none       Primary Th1 act       Lung Microvascular EC               TNFalpha + IL-1beta       Primary Th2 act   0.0   Microvascular Dermal EC               none       Primary Tr1 act   0.0   Microsvasular Dermal EC   0.0               TNFalpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   0.0               TNFalpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium   0.0               none       Primary Tr1 rest   0.0   Small airway epithelium   0.7               TNFalpha + IL-1beta       CD45RA CD4   0.0   Coronery artery SMC rest   0.0       lymphocyte act       CD45RO CD4   0.0   Coronery artery SMC   0.0       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   2.2       Secondary CD8   0.0   Astrocytes TNFalpha +   0.0       lymphocyte rest       IL-1beta       Secondary CD8   0.0   KU-812 (Basophil) rest   0.0       lymphocyte act       CD4 lymphocyte none   0.7   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.0   CCD1106 (Keratinocytes   0.0       CD95 CH11       none       LAK cells rest   0.6   CCD1106 (Keratinocytes)   0.0               TNFalpha + IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   5.4       LAK cells IL-2 + IL-12   0.0   Lupus kidney   1.2       LAK cells IL-2 + IFN   0.0   NCI-H292 none   0.4       gamma       LAK cells IL-2 + IL-18   0.0   NCI-H292 IL-4   0.0       LAK cells   0.0   NCI-H292 IL-9   0.0       PMA/ionomycin       NK Cells IL-2 rest   0.0   NCI-H292 IL-13   0.0       Two Way MLR 3 day   2.6   NCI-H292 IFN gamma   0.0       Two Way MLR 5 day   1.9   HPAEC none   0.0       Two Way MLR 7 day   0.0   HPAEC TNF alpha + IL-1   0.0               beta       PBMC rest   10.6   Lung fibroblast none   0.0       PBMC PWM   2.8   Lung fibroblast TNF alpha +   0.0               IL-1 beta       PBMC PHA-L   0.0   Lung fibroblast IL-4   0.0       Ramos (B cell) none   0.0   Lung fibroblast IL-9   0.0       Ramos (B cell)   0.0   Lung fibroblast IL-13   0.0       ionomycin       B lymphocytes PWM   0.0   Lung fibroblast IFN   0.0               gamma       B lymphocytes CD40L   0.0   Dermal fibroblast   0.0       and IL-4       CCD1070 rest       EOL-1 dbcAMP   33.0   Dermal fibroblast   0.4               CCD1070 TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast   0.0       PMA/ionomycin       CCD1070 IL-1 beta       Dendritic cells none   0.0   Dermal fibroblast IFN   0.0               gamma       Dendritic cells LPS   0.0   Dermal fibroblast IL-4   0.0       Dendritic cells anti-   0.0   IBD Colitis 2   0.0       CD40       Monocytes rest   100.0   IBD Crohn&#39;s   0.0       Monocytes LPS   23.5   Colon   7.9       Macrophages rest   7.9   Lung   1.8       Macrophages LPS   20.6   Thymus   10.7       HUVEC none   0.0   Kidney   0.0       HUVEC starved   0.0                    
     [0653]               TABLE ME                          Panel CNS_1                                 Rel. Exp. (%) Ag1970,       Rel. Exp. (%) Ag1970,       Tissue Name   Run 186412668   Tissue Name   Run 186412668                                     BA4 Control   9.7   BA17 PSP   0.5       BA4 Control2   16.5   BA17 PSP2   3.3       BA4   3.3   Sub Nigra Control   100.0       Alzheimer&#39;s2       BA4 Parkinson&#39;s   30.4   Sub Nigra Control2   63.3       BA4   21.2   SubNigra   14.6       Parkinson&#39;s2       Alzheimer&#39;s2       BA4   17.7   SubNigra   51.1       Huntington&#39;s       Parkinson&#39;s2       BA4   4.5   Sub Nigra   56.3       Huntington&#39;s2       Huntington&#39;s       BA4 PSP   2.8   Sub Nigra   57.8               Huntington&#39;s2       BA4 PSP2   9.1   Sub Nigra PSP2   13.1       BA4 Depression   10.9   SubNigra   18.4               Depression       BA4   1.2   Sub Nigra   4.7       Depression2       Depression2       BA7 Control   14.3   Glob Palladus   17.2               Control       BA7 Control2   15.7   Glob Palladus   16.2               Control2       BA7   4.9   Glob Palladus   9.7       Alzheimer&#39;s2       Alzheimer&#39;s       BA7 Parkinson&#39;s   15.1   Glob Palladus   6.2               Alzheimer&#39;s2       BA7   13.3   Glob Palladus   58.2       Parkinson&#39;s2       Parkinson&#39;s       BA7   19.5   Glob Palladus   10.7       Huntington&#39;s       Parkinson&#39;s2       BA7   62.9   Glob Palladus PSP   4.7       Huntington&#39;s2       BA7 PSP   7.6   Glob Palladus PSP2   2.6       BA7 PSP2   8.8   Glob Palladus   7.7               Depression       BA7 Depression   8.4   Temp Pole Control   7.3       BA9 Control   4.4   Temp Pole Control2   30.1       BA9 Control2   39.5   Temp Pole   1.7               Alzheimer&#39;s       BA9 Alzheimer&#39;s   1.2   Temp Pole   1.6               Alzheimer&#39;s2       BA9   3.0   Temp Pole   13.4       Alzheimer&#39;s2       Parkinson&#39;s       BA9 Parkinson&#39;s   16.8   Temp Pole   9.4               Parkinson&#39;s2       BA9   19.5   Temp Pole   11.3       Parkinson&#39;s2       Huntington&#39;s       BA9   15.4   Temp Pole PSP   1.2       Huntington&#39;s       BA9   9.4   Temp Pole PSP2   0.3       Huntington&#39;s2       BA9 PSP   3.1   Temp Pole   4.9               Depression2       BA9 PSP2   3.5   Cing Gyr Control   36.3       BA9 Depression   2.5   Cing Gyr Control2   9.7       BA9   3.1   Cing Gyr   13.2       Depression2       Alzheimer&#39;s       BA17 Control   35.1   Cing Gyr   4.8               Alzheimer&#39;s2       BA17 Control2   17.4   Cing Gyr   31.6               Parkinson&#39;s       BA17   3.8   Cing Gyr   23.2       Alzheimer&#39;s2       Parkinson&#39;s2       BA17   39.5   Cing Gyr   30.4       Parkinson&#39;s       Huntington&#39;s       BA17   29.9   Cing Gyr   48.3       Parkinson&#39;s2       Huntington&#39;s2       BA17   11.5   Cing Gyr PSP   13.7       Huntington&#39;s       BA17   28.5   Cing Gyr PSP2   3.7       Huntington&#39;s2       BA17   7.8   Cing Gyr Depression   6.0       Depression       BA17   21.0   Cing Gyr   14.8       Depression2       Depression2                    
     [0654] CNS_neurodegeneration_v1.0 Summary: Ag1970 This panel does not show differential expression of the CG97358-01 gene in Alzheimer&#39;s disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.3D for discussion of this gene in the central nervous system.  
     [0655] Panel 1.3D Summary: Ag1970 Significant expression of the CG97358-01 gene appears to be restricted to the brain, with highest expression in the hippocampus and substantia nigra (CTs=26.9). Thus, this gene would be useful for distinguishing brain tissue from non-neural tissue. The CG97358-01 gene encodes a homolog of rat Olg-1 bHLH protein. Olg-1 gene, a member of oligodendrocyte lineage gene family, is associated with development of oligodendrocytes in the vertebrate central nervous system (CNS) (Lu et al., 2000, Neuron 25(2):317-29, PMID: 10719888). Therefore, therapeutic modulation of this gene product may be beneficial in the treatment of neurodegenerative diseases.  
     [0656] Panel 4D Summary: Ag1970 Significant expression of the CG97358-01 gene is seen in resting monocytes (CT=30.8), with expression downregulated upon treatment with LPS. The expression of this gene in resting cells of this lineage suggests that the protein encoded by this transcript may be involved in normal immunological processes associated with immune homeostasis.  
     [0657] Panel CNS — 1 Summary: Ag1970 This panel confirms expression of the CG97358-01 gene in the brain. Please see Panel 1.3D for discussion of this gene in the central nervous system.  
     N. NOV34a (CG97378-01): SNRNP-isoform1, submitted to study DDNPAT on 05/11/01 by bzerhuse; clone status=FIS; novelty=Novel; ORF start=157, ORF stop=400, frame=1; 3390 bp.  
     [0658] Expression of gene CG97378-01 was assessed using the primer-probe set Ag1986, described in Table NA. Results of the RTQ-PCR runs are shown in Tables NB, NC, ND and NE.  
               TABLE NA                          Probe Name Ag1986                                             Start   SEQ ID       Primers   Sequences   Length   Position   No               Forward   5′-caggctggtcttgaagtccta-3′   21   2594   127               Probe   TET-5′-agtgttcctcctgcctcccaaagtgt-3′-TAMRA   26   2562   128               Reverse   5′-gaggtggctcacacctgtaat-3′   21   2537   129                  
 
     [0659]               TABLE NB                          Panel 1.3D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag1986, Run       Ag1986, Run       Tissue Name   165618029   Tissue Name   165618029                                     Liver   0.0   Kidney (fetal)   0.0       adenocarcinoma       Pancreas   0.0   Renal ca. 786-0   0.0       Pancreatic ca.   0.0   Renal ca. A498   1.0       CAPAN 2       Adrenal gland   0.0   Renal ca. RXF 393   0.0       Thyroid   0.0   Renal ca. ACHN   0.0       Salivary gland   0.0   Renal ca. UO-31   0.0       Pituitary gland   0.0   Renal ca. TK-10   0.0       Brain (fetal)   0.0   Liver   0.0       Brain (whole)   0.0   Liver (fetal)   0.0       Brain (amygdala)   0.0   Liver ca.   0.0               (hepatoblast) HepG2       Brain   0.0   Lung   0.0       (cerebellum)       Brain   0.0   Lung (fetal)   0.0       (hippocampus)       Brain (substantia   0.0   Lung ca. (small cell)   0.0       nigra)       LX-1       Brain (thalamus)   0.0   Lung ca. (small cell)   1.1               NCI-H69       Cerebral Cortex   0.0   Lung ca. (s.cell   0.0               var.) SHP-77       Spinal cord   0.0   Lung ca. (large   0.0               cell) NCI-H460       glio/astro   0.0   Lung ca. (non-sm.   0.0       U87-MG       cell) A549       glio/astro   0.0   Lung ca. (non-   0.0       U-118-MG       s.cell) NCI-H23       astrocytoma   0.0   Lung ca. (non-   0.0       SW1783       s.cell) HOP-62       neuro*; met   0.0   Lung ca. (non-s.cl)   0.0       SK-N-AS       NCI-H522       astrocytoma   0.0   Lung ca. (squam.)   0.0       SF-539       SW 900       astrocytoma   0.0   Lung ca. (squam.)   0.0       SNB-75       NCI-H596       glioma SNB-19   0.0   Mammary gland   0.0       glioma U251   4.4   Breast ca.* (pl.ef)   23.2               MCF-7       glioma SF-295   0.0   Breast ca.* (pl.ef)   0.0               MDA-MB-231       Heart (fetal)   0.0   Breast ca.* (pl.ef)   0.0               T47D       Heart   0.0   Breast ca. BT-549   5.1       Skeletal muscle   0.0   Breast ca. MDA-N   0.0       (fetal)       Skeletal muscle   0.0   Ovary   0.0       Bone marrow   0.0   Ovarian Ca.   0.0               OVCAR-3       Thymus   0.0   Ovarian ca.   0.0               OVCAR-4       Spleen   0.0   Ovarian ca.   0.0               OVCAR-5       Lymph node   0.0   Ovarian ca.   0.0               OVCAR-8       Colorectal   0.0   Ovarian ca.   0.0               IGROV-1       Stomach   0.0   Ovarian ca.*   0.0               (ascites) SK-OV-3       Small intestine   0.0   Uterus   0.0       Colon ca. SW480   0.0   Placenta   10.6       Colon ca.*   0.7   Prostate   0.0       SW620(SW480       met)       Colon ca. HT29   0.0   Prostate ca.* (bone   2.5               met)PC-3       Colon ca.   0.0   Testis   0.0       HCT-116       Colon ca. CaCo-2   0.0   Melanoma   0.0               Hs688(A).T       Colon ca.   0.0   Melanoma* (met)   0.7       tissue(ODO3866)       Hs688(B).T       Colon ca.   8.1   Melanoma UACC-   0.0       HCC-2998       62       Gastric ca.* (liver   3.7   Melanoma M14   0.0       met) NCI-N87       Bladder   0.0   Melanoma LOX   0.0               IMVI       Trachea   0.0   Melanoma* (met)   0.0               SK-MEL-5       Kidney   0.0   Adipose   100.0                    
     [0660]               TABLE NC                          Panel 2.2                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag1986, Run       Ag1986, Run       Tissue Name   174229404   Tissue Name   174229404                                     Normal Colon   0.0   Kidney Margin   0.0               (OD04348)       Colon cancer   17.8   Kidney malignant   0.0       (OD06064)       cancer (OD06204B)       Colon Margin   19.6   Kidney normal adjacent   0.0       (OD06064)       tissue (OD06204E)       Colon cancer   0.0   Kidney Cancer   0.0       (OD06159)       (OD04450-01)       Colon Margin   0.0   Kidney Margin   0.0       (OD06159)       (OD04450-03)       Colon cancer   0.0   Kidney Cancer   0.0       (OD06297-04)       8120613       Colon Margin   0.0   Kidney Margin   0.0       (OD06297-05)       8120614       CC Gr.2 ascend colon   0.0   Kidney Cancer   0.0       (ODO3921)       9010320       CC Margin (ODO3921)   0.0   Kidney Margin   0.0               9010321       Colon cancer metastasis   0.0   Kidney Cancer   0.0       (OD06104)       8120607       Lung Margin   0.0   Kidney Margin   0.0       (OD06104)       8120608       Colon mets to lung   0.0   Normal Uterus   8.8       (O`D04451-01)       Lung Margin   4.9   Uterine Cancer 064011   0.0       (OD04451-02)       Normal Prostate   1.2   Normal Thyroid   0.0       Prostate Cancer   0.0   Thyroid Cancer 064010   0.0       (OD04410)       Prostate Margin   0.0   Thyroid Cancer   0.0       (OD04410)       A302152       Normal Ovary   0.0   Thyroid Margin   0.0               A302153       Ovarian cancer   0.0   Normal Breast   3.1       (OD06283-03)       Ovarian Margin   100.0   Breast Cancer   0.0       (OD06283-07)       (OD04566)       Ovarian Cancer 064008   0.0   Breast Cancer 1024   2.2       Ovarian cancer   7.4   Breast Cancer   0.0       (OD06145)       (OD04590-01)       Ovarian Margin   13.3   Breast Cancer Mets   0.0       (OD06145)       (OD04590-03)       Ovarian cancer   0.0   Breast Cancer   0.0       (OD06455-03)       Metastasis (OD04655-               05)       Ovarian Margin   91.4   Breast Cancer 064006   0.0       (OD06455-07)       Normal Lung   0.0   Breast Cancer 9100266   13.6       Invasive poor diff. lung   0.0   Breast Margin 9100265   1.6       adeno (ODO4945-01       Lung Margin   2.1   Breast Cancer A209073   1.3       (ODO4945-03)       Lung Malignant Cancer   0.0   Breast Margin   0.0       (OD03126)       A2090734       Lung Margin   3.6   Breast cancer   0.0       (OD03126)       (OD06083)       Lung Cancer   0.0   Breast cancer node   0.0       (OD05014A)       metastasis (OD06083)       Lung Margin   6.8   Normal Liver   0.0       (OD05014B)       Lung cancer (OD06081)   0.0   Liver Cancer 1026   0.0       Lung Margin   0.0   Liver Cancer 1025   1.9       (OD06081)       Lung Cancer   0.0   Liver Cancer 6004-T   2.6       (OD04237-01)       Lung Margin   2.6   Liver Tissue 6004-N   0.0       (OD04237-02)       Ocular Melanoma   0.0   Liver Cancer 6005-T   0.0       Metastasis       Ocular Melanoma   0.0   Liver Tissue 6005-N   0.0       Margin (Liver)       Melanoma Metastasis   0.0   Liver Cancer 064003   0.0       Melanoma Margin   2.0   Normal Bladder   0.0       (Lung)       Normal Kidney   0.0   Bladder Cancer 1023   0.0       Kidney Ca, Nuclear   0.0   Bladder Cancer   0.0       grade 2 (OD04338)       A302173       Kidney Margin   0.0   Normal Stomach   0.0       (OD04338)       Kidney Ca Nuclear   0.0   Gastric Cancer   0.0       grade 1/2 (OD04339)       9060397       Kidney Margin   0.0   Stomach Margin   0.0       (OD04339)       9060396       Kidney Ca, Clear cell   0.0   Gastric Cancer   0.0       type (OD04340)       9060395       Kidney Margin   0.0   Stomach Margin   8.9       (OD04340)       9060394       Kidney Ca, Nuclear   4.3   Gastric Cancer 064005   0.0       grade 3 (OD04348)                    
     [0661]               TABLE ND                          Panel 4D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag1986, Run       Ag1986, Run       Tissue Name   162308224   Tissue Name   162308224                                     Secondary Th1 act   6.5   HUVEC IL-1beta   4.2       Secondary Th2 act   1.8   HUVEC IFN gamma   5.1       Secondary Tr1 act   8.0   HUVEC TNF alpha + IFN   5.6               gamma       Secondary Th1 rest   0.2   HUVEC TNF alpha + IL4   7.6       Secondary Th2 rest   0.5   HUVEC IL-11   2.9       Secondary Tr1 rest   1.7   Lung Microvascular EC   1.3               none       Primary Th1 act   6.3   Lung Microvascular EC   7.8               TNFalpha + IL-1beta       Primary Th2 act   3.0   Microvascular Dermal EC   0.2               none       Primary Tr1 act   8.3   Microsvasular Dermal EC   17.1               TNFalpha + IL-1beta       Primary Th1 rest   2.7   Bronchial epithelium   22.1               TNFalpha + IL1beta       Primary Th2 rest   2.1   Small airway epithelium   2.3               none       Primary Tr1 rest   2.2   Small airway epithelium   19.2               TNFalpha + IL-1beta           CD45RA CD4   8.5   Coronery artery SMC rest   1.2       lymphocyte act       CD45RO CD4   10.1   Coronery artery SMC   0.5       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   3.9   Astrocytes rest   3.4       Secondary CD8   7.5   Astrocytes TNFalpha +   10.6       lymphocyte rest       IL-1beta       Secondary CD8   5.4   KU-812 (Basophil) rest   0.4       lymphocyte act       CD4 lymphocyte none   2.5   KU-812 (Basophil)   3.5               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.4   CCD1106 (Keratinocytes)   4.1       CD95 CH11       none       LAK cells rest   22.1   CCD1106 (Keratinocytes)   2.8               TNFalpha + IL-1beta       LAK cells IL-2   4.6   Liver cirrhosis   0.0       LAK cells IL-2 + IL-12   34.9   Lupus kidney   0.0       LAK cells IL-2 + IFN   13.8   NCI-H292 none   0.4       gamma       LAK cells IL-2 + IL-18   9.0   NCI-H292 IL-4   100.0       LAK cells   97.9   NCI-H292 IL-9   4.8       PMA/ionomycin       NK Cells IL-2 rest   2.6   NCI-H292 IL-13   31.2       Two Way MLR 3 day   21.0   NCI-H292 IFN gamma   4.4       Two Way MLR 5 day   22.4   HPAEC none   0.4       Two Way MLR 7 day   3.4   HPAEC TNF alpha + IL-1   8.4               beta       PBMC rest   7.2   Lung fibroblast none   0.3       PBMC PWM   62.0   Lung fibroblast TNF   3.6               alpha + IL-1 beta       PBMC PHA-L   6.1   Lung fibroblast IL-4   4.2       Ramos (B cell) none   1.5   Lung fibroblast IL-9   0.4       Ramos (B cell)   40.1   Lung fibroblast IL-13   1.2       ionomycin       B lymphocytes PWM   47.3   Lung fibroblast IFN   0.7               gamma       B lymphocytes CD40L   5.3   Dermal fibroblast   1.5       and IL-4       CCD1070 rest       EOL-1 dbcAMP   0.2   Dermal fibroblast   5.7               CCD1070 TNF alpha       EOL-1 dbcAMP   7.2   Dermal fibroblast   0.8       PMA/ionomycin       CCD1070 IL-1 beta       Dendritic cells none   11.8   Dermal fibroblast IFN   0.2               gamma       Dendritic cells LPS   93.3   Dermal fibroblast IL-4   0.0       Dendritic cells anti-   6.7   IBD Colitis 2   0.8       CD40       Monocytes rest   5.3   IBD Crohn&#39;s   0.1       Monocytes LPS   56.3   Colon   0.4       Macrophages rest   4.5   Lung   0.3       Macrophages LPS   23.8   Thymus   0.4       HUVEC none   1.6   Kidney   9.7       HUVEC starved   2.2                    
     [0662]               TABLE NE                          Panel 5D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag1986, Run       Ag1986, Run       Tissue Name   169269866   Tissue Name   169269866                                     97457_Patient-   1.8   94709_Donor 2 AM-A_adipose   0.0       02go_adipose       97476_Patient-   93.3   94710_Donor 2 AM-B_adipose   1.4       07sk_skeletal muscle       97477_Patient-   0.0   94711_Donor 2 AM-C_adipose   0.0       07ut_uterus       97478_Patient-   62.4   94712_Donor 2 AD-A_adipose   0.0       07pl_placenta       97481_Patient-   39.5   94713_Donor 2 AD-B_adipose   0.0       08sk_skeletal muscle       97482_Patient-   1.0   94714_Donor 2 AD-C_adipose   0.0       08ut_uterus       97483_Patient-   72.7   94742_Donor 3 U-   0.0       08pl_placenta       A_Mesenchymal Stem Cells       97486_Patient-   0.0   94743_Donor 3 U-       09sk_skeletal muscle       B_Mesenchymal Stem Cells   0.0       97487_Patient-   4.2   94730_Donor 3 AM-A_adipose   0.0       09ut_uterus       97488_Patient-   13.3   94731_Donor 3 AM-B_adipose   0.0       09pl_placenta       97492_Patient-   0.0   94732_Donor 3 AM-C_adipose   0.0       10ut_uterus       97493_Patient-   100.0   94733_Donor 3 AD-A_adipose   0.0       10pl_placenta       97495_Patient-   39.8   94734_Donor 3 AD-B_adipose   0 0       11go_adipose       97496_Patient-   1.8   94735_Donor 3 AD-C_adipose   0.0       11sk_skeletal muscle       97497_Patient-   0.0   77138_Liver_HepG2untreated   3.2       11ut_uterus       97498_Patient-   24.0   73556_Heart_Cardiac stromal   0.0       11pl_placenta       cells (primary)       97500_Patient-   22.7   81735_Small Intestine   00       12go_adipose       97501_Patient-   0.0   72409_Kidney_Proximal   1.7       12sk_skeletal muscle       Convoluted Tubule       97502_Patient-   0.9   82685_Small intestine_Duodenum   0.0       12ut_uterus       97503_Patient-   3.1   90650_Adrenal_Adrenocortical   0.0       12pl_placenta       adenoma       94721_Donor 2 U-   0.0   72410_Kidney_HRCE   0.0       A_Mesenchymal       Stem Cells       94722_Donor 2 U-   0.0   72411_Kidney_HRE   0.0       B_Mesenchymal Stem       Cells       94723_Donor 2 U-   0.0   73139_Uterus_Uterine smooth   3.2       C_Mesenchymal Stem       muscle cells       Cells                    
     [0663] Panel 1.3D Summary: Ag1986 Significant expression of the CG97378-01 gene is restricted to adipose and a breast cancer cell line (CTs=32.8-34.9). Thus, expression of this gene may be used to differentiate these samples from other samples on this panel and as a marker of adipose. This expression also suggests that this gene product may be involved in the pathogenesis and/or diagnosis of obesity.  
     [0664] Panel 2.2 Summary: Ag1986 Significant expression of the CG97378-01 gene is restricted to ovarian tissue (CT=33). Thus, expression of this gene could be used to differentiate ovarian derived tissues from other samples on this panel and as a marker of ovarian tissue. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of ovarian cancer.  
     [0665] Panel 4D Summary: Ag1986 Significant expression of the CG97378-01 gene is highest in IL-4 treated NCI-H292 cells (CT=28.04). In addition, prominent levels of expression are seen in LPS treated dendrocytes, macrophages and monocytes, TNF-alpha and IL-1 beta treated bronchial epithelium, small airway epithelium and microvascular dermal ECs, PMA/ionomycin stimulated LAK cells, ionomycin stimulated B cells, and PWM activated PBMCs and B lymphocytes. This pattern of expression suggests that the protein encoded by this transcript may be important in monocytic and dendritic cell differentiation and activation. Therefore, regulating the expression of this transcript or the function of the protein it encodes may alter the types and levels of monocytic cells regulated by cytokine and chemokine production and T cell activation. Therapeutics designed with the protein encoded by this transcript could therefore be important for the treatment of asthma, emphysema, inflammatory bowel disease, arthritis, psoriasis and any other disease where the activated immune cells listed above play a role.  
     [0666] Moderate levels of expression of this gene is also seen in kidney sample. Therefore, therapeutic modulation of this gene may be beneficial in the treatment of autoimmune and inflammatory diseases that affect kidney including lupus and glomerulonephritis.  
     [0667] Panel 5D Summary: Ag1986 Expression of the CG97378-01 gene is seen exclusively in placent, skeletal muscle and adipose. Thus, expression of this gene could be used to differentiate these samples from other samples on this panel and as a marker of these tissues. In addition, therapeutic modulation of this gene may be useful in treatment of endocrine/metabolically related diseases, such as obesity and diabetes.  
     O. NOV36a (CG99852-01): Novel Gene Containing NUDIX Hydrolase Domain  
     [0668] Expression of gene CG99852-01 was assessed using the primer-probe set Ag4159, described in Table OA. Results of the RTQ-PCR runs are shown in Tables OB, OC, OD and OE.  
               TABLE OA                          Probe Name Ag4159                                             Start   SEQ ID       Primers   Sequences   Length   Position   No               Forward   5′-gatgctctcccttctgatgag-3′   21   398   130               Probe   TET-5′-ccggttagggtccttaatcacatcga-3′-TAMRA   26   428   131               Reverse   5′-cttccctgatcacgttgtactc-3′   22   474   132                  
 
     [0669]               TABLE OB                          CNS_neurodegeneration_v1.0                                 Rel. Ex. (%)       Rel. Ex. (%)           Ag4159,       Ag4159,           Run       Run       Tissue Name   215337525   Tissue Name   215337525                                     AD 1 Hippo   47.6   Control (Path) 3   2.1               Temporal Ctx       AD 2 Hippo   29.3   Control (Path) 4   45.1               Temporal Ctx       AD 3 Hippo   16.6   AD 1 Occipital Ctx   16.0       AD 4 Hippo   22.4   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   100.0   AD 3 Occipital Ctx   9.7       AD 6 Hippo   69.7   AD 4 Occipital Ctx   22.7       Control 2 Hippo   42.9   AD 5 Occipital Ctx   19.3       Control 4 Hippo   4.4   AD 6 Occipital Ctx   26.1       Control (Path) 3   0.0   Control 1 Occipital   8.3       Hippo       Ctx       AD 1 Temporal Ctx   43.5   Control 2 Occipital   61.1               Ctx       AD 2 Temporal Ctx   46.0   Control 3 Occipital   17.7               Ctx       AD 3 Temporal Ctx   18.4   Control 4 Occipital   14.6               Ctx       AD 4 Temporal Ctx   26.6   Control (Path) 1   98.6               Occipital Ctx       AD 5 Inf Temporal   95.9   Control (Path) 2   32.8       Ctx       Occipital Ctx       AD 5 SupTemporal   59.5   Control (Path) 3   7.3       Ctx       Occipital Ctx       AD 6 Inf Temporal   27.2   Control (Path)   44.4       Ctx       Occipital Ctx       AD 6 Sup Temporal   35.1   Control 1 Parietal   33.0       Ctx       Ctx       Control 1 Temporal   15.7   Control 2 Parietal   77.4       Ctx       Ctx       Control 2 Temporal   23.5   Control 3 Parietal   23.7       Ctx       Ctx       Control 3 Temporal   0.0   Control (Path) 1   62.4       Ctx       Parietal Ctx       Control 4 Temporal   32.8   Control (Path) 2   48.6       Ctx       Parietal Ctx       Control (Path) 1   56.3   Control (Path) 3   11.7       Temporal Ctx       Parietal Ctx       Control (Path) 2   92.0   Control (Path) 4   66.0       Temporal Ctx       Parietal Ctx                    
     [0670]               TABLE OC                          General_screening_panel_v1.4                                 Rel. Exp. (%) Ag4159,       Rel. Exp. (%) Ag4159,       Tissue Name   Run 221297228   Tissue Name   Run 221297228                                     Adipose   0.2   Renal ca. TK-10   4.0       Melanoma*   0.2   Bladder   8.2       Hs688(A).T       Melanoma*   0.9   Gastric ca. (liver met.)   3.9       Hs688(B).T       NCI-N87       Melanoma* M14   2.0   Gastric ca. KATO III   11.9       Melanoma*   0.9   Colon ca. SW-948   4.5       LOXIMVI       Melanoma* SK-   6.9   Colon ca. SW480   22.5       MEL-5       Squamous cell   6.2   Colon ca.* (SW480   6.3       carcinoma SCC-4       met) SW620       Testis Pool   1.9   Colon ca. HT29   2.3       Prostate ca.* (bone   4.4   Colon ca. HCT-116   13.8       met) PC-3       Prostate Pool   4.0   Colon ca. CaCo-2   14.2       Placenta   1.6   Colon cancer tissue   6.8       Uterus Pool   0.8   Colon ca. SW1116   5.3       Ovarian ca.   4.0   Colon ca. Colo-205   1.1       OVCAR-3       Ovarian ca. SK-OV-   8.5   Colon ca. SW-48   2.1       3       Ovarian ca.   7.7   Colon Pool   4.3       OVCAR-4       Ovarian ca.   71.2   Small Intestine Pool   1.2       OVCAR-5       Ovarian ca. IGROV-   3.6   Stomach Pool   1.4       1       Ovarian ca.   8.7   Bone Marrow Pool   0.7       OVCAR-8       Ovary   1.8   Fetal Heart   1.4       Breast ca. MCF-7   2.7   Heart Pool   1.9       Breast ca. MDA-   3.3   Lymph Node Pool   0.8       MB-231       Breast ca. BT 549   5.3   Fetal Skeletal Muscle   1.8       Breast ca. T47D   100.0   Skeletal Muscle Pool   0.7       Breast ca. MDA-N   1.8   Spleen Pool   1.0       Breast Pool   1.8   Thymus Pool   5.3       Trachea   2.0   CNS cancer (glio/astro)   9.3               U87-MG       Lung   0.8   CNS cancer (glio/astro)   0.7               U-118-MG       Fetal Lung   4.8   CNS cancer   0.4               (neuro; met) SK-N-AS       Lung ca. NCI-N417   1.9   CNS cancer (astro) SF-   1.5               539       Lung ca. LX-1   12.0   CNS cancer (astro)   3.8               SNB-75       Lung ca. NCI-H146   8.2   CNS cancer (glio)   2.5               SNB-19       Lung ca. SHP-77   21.3   CNS cancer (glio) SF-   5.0               295       Lung ca. A549   2.8   Brain (Amygdala) Pool   2.1       Lung ca. NCI-H526   6.6   Brain (cerebellum)   3.8       Lung ca. NCI-H23   5.4   Brain (fetal)   5.3       Lung ca. NCI-H460   3.1   Brain (Hippocampus)   3.0               Pool       Lung ca. HOP-62   1.0   Cerebral Cortex Pool   2.0       Lung ca. NCI-H522   24.8   Brain (Substantia nigra)   2.5               Pool       Liver   0.4   Brain (Thalamus) Pool   1.8       Fetal Liver   0.3   Brain (whole)   0.7       Liver ca. HepG2   1.5   Spinal Cord Pool   0.6       Kidney Pool   4.6   Adrenal Gland   4.4       Fetal Kidney   5.7   Pituitary gland Pool   3.1       Renal ca. 786-0   2.1   Salivary Gland   0.4       Renal ca. A498   1.7   Thyroid (female)   2.5       Renal ca. ACHN   3.7   Pancreatic ca.   10.2               CAPAN2       Renal ca. UO-31   4.4   Pancreas Pool   10.2                    
     [0671]               TABLE OD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4159, Run       Ag4159, Run       Tissue Name   173123947   Tissue Name   173123947                                     Secondary Th1 act   3.1   HUVEC IL-1beta   4.7       Secondary Th2 act   5.2   HUVEC IFN gamma   10.6       Secondary Tr1 act   2.4   HUVEC TNF alpha + IFN   3.9               gamma       Secondary Th1 rest   3.2   HUVEC TNF alpha + IL4   3.3       Secondary Th2 rest   3.0   HUVEC IL-11   4.5       Secondary Tr1 rest   4.5   Lung Microvascular EC   9.5               none       Primary Th1 act   0.0   Lung Microvascular EC   7.1               TNFalpha + IL-1 beta       Primary Th2 act   1.7   Microvascular Dermal EC   8.2               none       Primary Tr1 act   1.6   Microsvasular Dermal EC   3.2               TNFalpha + IL-1beta       Primary Th1 rest   2.9   Bronchial epithelium   1.7               TNFalpha + IL1beta       Primary Th2 rest   0.3   Small airway epithelium   2.4               none       Primary Tr1 rest   5.7   Small airway epithelium   2.7               TNFalpha + IL-1beta       CD45RA CD4   1.0   Coronery artery SMC rest   0.4       lymphocyte act       CD45RO CD4   1.8   Coronery artery SMC   0.7       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   0.5   Astrocytes rest   0.7       Secondary CD8   0.6   Astrocytes TNFalpha +   1.8       lymphocyte rest       IL-1beta       Secondary CD8   0.3   KU-812 (Basophil) rest   4.5       lymphocyte act       CD4 lymphocyte none   2.3   KU-812 (Basophil)   2.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   4.1   CCD1106 (Keratinocytes)   6.7       CD95 CH11       none       LAK cells rest   2.2   CCD1106 (Keratinocytes)   3.0               TNFalpha + IL-1beta       LAK cells IL-2   2.6   Liver cirrhosis   1.6       LAK cells IL-2 + IL-12   2.1   NCI-H292 none   4.7       LAK cells IL-2 + IFN   4.0   NCI-H292 IL-4   5.1       gamma       LAK cells IL-2 + IL-18   4.8   NCI-H292 IL-9   8.3       LAK cells   1.1   NCI-H292 IL-13   11.7       PMA/ionomycin       NK Cells IL-2 rest   13.8   NCI-H292 IFN gamma   8.2       Two Way MLR 3 day   3.9   HPAEC none   2.2       Two Way MLR 5 day   2.5   HPAEC TNF alpha + IL-1   1.7               beta       Two Way MLR 7 day   1.1   Lung fibroblast none   1.1       PBMC rest   0.3   Lung fibroblast TNF alpha +   0.6               IL-1 beta       PBMC PWM   1.8   Lung fibroblast IL-4   0.0       PBMC PHA-L   2.1   Lung fibroblast IL-9   1.2       Ramos (B cell) none   0.6   Lung fibroblast IL-13   3.5       Ramos (B cell)   0.8   Lung fibroblast IFN   2.1       ionomycin       gamma       B lymphocytes PWM   0.8   Dermal fibroblast   0.5               CCD1070 rest       B lymphocytes CD40L   3.2   Dermal fibroblast   1.7       and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   3.5   Dermal fibroblast   0.5               CCD1070 IL-1 beta       EOL-1 dbcAMP   7.6   Dermal fibroblast IFN   2.0       PMA/ionomycin       gamma       Dendritic cells none   3.4   Dermal fibroblast IL-4   2.5       Dendritic cells LPS   0.9   Dermal Fibroblasts rest   4.0       Dendritic cells anti-   1.1   Neutrophils TNFa + LPS   0.8       CD40       Monocytes rest   2.5   Neutrophils rest   3.4       Monocytes LPS   3.5   Colon   4.9       Macrophages rest   0.5   Lung   5.0       Macrophages LPS   1.1   Thymus   13.0       HUVEC none   2.0   Kidney   100.0       HUVEC starved   7.9                    
     [0672]               TABLE OE                          general oncology screening panel_v_2.4                                 Rel. Exp. (%) Ag4159,       Rel. Exp. (%) Ag4159,       Tissue Name   Run 268624151   Tissue Name   Run 268624151                                     Colon cancer 1   19.1   Bladder cancer NAT 2   0.0       Colon NAT 1   9.5   Bladder cancer NAT 3   0.8       Colon cancer 2   4.1   Bladder cancer NAT 4   4.6       Colon cancer NAT   3.2   Adenocarcinoma of the   6.8       2       prostate 1       Colon cancer 3   12.0   Adenocarcinoma of the   1.7               prostate 2       Colon cancer NAT   7.0   Adenocarcinoma of the   3.7       3       prostate 3       Colon malignant   6.3   Adenocarcinoma of the   24.1       cancer 4       prostate 4       Colon normal   2.9   Prostate cancer NAT 5   6.3       adjacent tissue 4       Lung cancer 1   7.0   Adenocarcinoma of the   2.7               prostate 6       Lung NAT 1   0.8   Adenocarcinoma of the   3.8               prostate 7       Lung cancer 2   11.2   Adenocarcinoma of the   1.0               prostate 8       Lung NAT 2   0.3   Adenocarcinoma of the   12.1               prostate 9       Squamous cell   13.6   Prostate cancer NAT 10   1.0       carcinoma 3       Lung NAT 3   0.0   Kidney cancer 1   12.2       metastatic   6.3   KidneyNAT 1   16.5       melanoma 1       Melanoma 2   1.3   Kidney cancer 2   100.0       Melanoma 3   0.0   Kidney NAT 2   24.1       metastatic   12.0   Kidney cancer 3   57.0       melanoma 4       metastic   11.0   Kidney NAT 3   12.2       melanoma 5       Bladder cancer 1   0.0   Kidney cancer 4   6.8       Bladder cancer   0.0   Kidney NAT 4   5.9       NAT 1       Bladder cancer 2   0.7                    
     [0673] CNS_neurodegeneration_v1.0 Summary: Ag4159 This panel does not show differential expression of the CG99852-01 gene in Alzheimer&#39;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.  
     [0674] General_screening_panel_v1.4 Summary: Ag4159 Highest expression of the CG99852-01 gene is seen in a breast cancer cell line (CT=29.4). In addition, significant levels of expression are seen in a breast cancer cell line. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of ovarian and breast cancers.  
     [0675] Among tissues with metabolic function, this gene is expressed at low but significant levels in pituitary, adrenal gland, pancreas, and thyroid. 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.  
     [0676] This gene is also expressed at low levels in the CNS, including the hippocampus, substantia nigra, amygdala, and cerebellum. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0677] Panel 4.1D Summary: Ag4159 Highest expression of the CG99852-01 gene is seen in kidney (CT=29.6). Therefore, antibody or small molecule therapies designed with the protein encoded for by this gene could modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.  
     [0678] general oncology screening panel_v — 2.4 Summary: Ag4159 Highest expression of the CG99852-01 gene is seen in kidney cancer sample (CT=31). Moderate to low levels of expression of this gene is also seen in number of cancer samples including kidney, colon, lung, prostate cancers and metastatic melanoma. In addition, expression of this gene is higher in the cancers than in the normal adjacent tissue. Therefore, expression of this gene could be as a marker to detect the presence of these cancers.  
     Example D  
     Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences  
     [0679] Variant sequences are also included in this application. A variant sequence can include a single nucleotide polymorphism (SNP). A SNP can, in some instances, be referred to as a “cSNP” to denote that the nucleotide sequence containing the SNP originates as a cDNA. A SNP can arise in several ways. For example, a SNP may be due to a substitution of one nucleotide for another at the polymorphic site. Such a substitution can be either a transition or a transversion. A SNP can also arise from a deletion of a nucleotide or an insertion of a nucleotide, relative to a reference allele. In this case, the polymorphic site is a site at which one allele bears a gap with respect to a particular nucleotide in another allele. SNPs occurring within genes may result in an alteration of the amino acid encoded by the gene at the position of the SNP. Intragenic SNPs may also be silent, when a codon including a SNP encodes the same amino acid as a result of the redundancy of the genetic code. SNPs occurring outside the region of a gene, or in an intron within a gene, do not result in changes in any amino acid sequence of a protein but may result in altered regulation of the expression pattern. Examples include alteration in temporal expression, physiological response regulation, cell type expression regulation, intensity of expression, and stability of transcribed message.  
     [0680] SeqCalling assemblies produced by the exon linking process are selected and extended using the following criteria. Genomic clones having regions with 98% identity to all or part of the initial or extended sequence were identified by BLASTN searches using the relevant sequence to query human genomic databases. The genomic clones that resulted are selected for further analysis because this identity indicates that these clones contain the genomic locus for these SeqCalling assemblies. These sequences are analyzed for putative coding regions as well as for similarity to the known DNA and protein sequences. Programs used for these analyses include Grail, Genscan, BLAST, HMMER, FASTA, Hybrid and other relevant programs.  
     [0681] Some additional genomic regions may have also been identified because selected SeqCalling assemblies map to those regions. Such SeqCalling sequences may have overlapped with regions defined by homology or exon prediction. They may also be included because the location of the fragment was in the vicinity of genomic regions identified by similarity or exon prediction that had been included in the original predicted sequence. The sequence so identified is manually assembled and then may have been extended using one or more additional sequences taken from CuraGen Corporation&#39;s human SeqCalling database. SeqCalling fragments suitable for inclusion were identified by the CuraTools™ program SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed.  
     [0682] The regions defined by the procedures described above are then manually integrated and corrected for apparent inconsistencies that may have arisen, for example, from miscalled bases in the original fragments or from discrepancies between predicted exon junctions, EST locations and regions of sequence similarity, to derive the final sequence disclosed herein. When necessary, the process to identify and analyze SeqCalling assemblies and genomic clones is reiterated to derive the full length sequence (Alderborn et al., Determination of Single Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000).  
     [0683] Variants are reported individually but any combination of all or a select subset of variants are also included as contemplated NOVX embodiments of the invention.  
     Other Embodiments  
     [0684] Although particular embodiments have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims, which follow. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the invention without departing from the spirit and scope of the invention as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope of the following claims.  
     [0685] The claims presented are representative of the inventions disclosed herein. Other, unclaimed inventions are also contemplated. Applicants reserve the right to pursue such inventions in later claims.