Patent Publication Number: US-2003235882-A1

Title: Novel nucleic acids and polypeptides and methods of use thereof

Description:
RELATED APPLICATIONS  
     [0001] This application claims priority to U.S. Ser. No. 60/256,619 (Attorney Ref.: 21402-223), filed Dec. 19, 2000; U.S. Ser. No. 60/262,959 (Attorney Ref.: 21402-223A), filed Jan. 19, 2001; U.S. Ser. No. 60/272,408 (Attorney Ref.: 21402-223C1), filed Feb. 28, 2001; U.S. Ser. No. 60/285,189 (Attorney Ref.: 21402-222A), filed Apr. 20, 2001; U.S. Ser. No. 60/308,039 (Attorney Ref.: 21402-223D1), filed Jul. 26, 2001; and U.S. Ser. No. 60/311,266 (Attorney Ref.: 21402-223IFC-01), filed Aug. 9, 2001, each of which is incorporated by reference in its entirety. 
    
    
     
       FIELD OF THE INVENTION  
       [0002] The present 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  
       [0003] 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  
       [0004] The invention is based in part upon the discovery of nucleic acid sequences encoding novel polypeptides. The novel nucleic acids and polypeptides are referred to herein as NOVX, or NOV1, NOV2, NOV3, NOV4, NOV5, NOV6, NOV7, NOV8, NOV9, NOV10, NOV11 and NOV 12 nucleic acids and polypeptides. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid or polypeptide sequences.  
       [0005] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37. 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 NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38. 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37.  
       [0006] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37)or a complement of said oligonucleotide. Also included in the invention are substantially purified NOVX polypeptides (SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38). 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.  
       [0007] The invention also features antibodies that immunoselectively bind to NOVX polypeptides, or fragments, homologs, analogs or derivatives thereof.  
       [0008] 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.  
       [0009] 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.  
       [0010] 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.  
       [0011] The invention also includes methods to identify specific cell or tissue types based on their expression of a NOVX.  
       [0012] 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.  
       [0013] 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.  
       [0014] 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., Cancer, Hodgkin disease, Von Hippel-Lindau (VHL) syndrome, hypercalceimia, Endometriosis, Crohn&#39;s Disease, Xerostomia, Inflammatory bowel disease, Diverticular disease, fertility, Infertility, CNS disorders, osteoporosis, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, valve diseases, tuberous sclerosis, scleroderma, Hemophilia, obesity, Diabetes, Pancreatitis, transplantation recovery, Autoimmune disease, asthma, arthritis, Immunodeficiencies, Graft vesus host, Alzheimer&#39;s disease, Stroke, Parkinson&#39;s disease, Huntington&#39;s disease, Cerebral palsy, Epilepsy, Multiple sclerosis, Ataxia-telangiectasia, Behavioral disorders, Addiction, Anxiety, Pain, Muscular dystrophy, and/or other pathologies and disorders of the like.  
       [0015] 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.  
       [0016] 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.  
       [0017] 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.  
       [0018] 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.  
       [0019] 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.  
       [0020] 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.  
       [0021] 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.  
       [0022] 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.  
       [0023] 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.  
       [0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.  
       [0025] Other features and advantages of the invention will be apparent from the following detailed description and claims.  
       DETAILED DESCRIPTION OF THE INVENTION  
       [0026] The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences and their encoded polypeptides. 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                                             Nucleic                       Acid   Polypeptide       NOVX           SEQ ID   SEQ ID       No.   Internal Acc. No.   Homology   NO.   NO.                                          1a   CG-AC084364.5/   Stabilin   1   2           AC084364.5        1b   CG50736-10/11400078   Stabilin   3   4        1c   CG50736-09   CD44-like Precursor/   210   211               Fascilin domain        2a   CG142106342/CG50646-   Polydom   5   6           04        2b   CG50646-05   Polydom   7   8        3a   CG50273-01   Transmembrane Protein   9   10        3b   CG50273-02   Transmembrane IIIb   11   12               Protein        4   CG50289-01   Serine Protease   13   14        5a   CG50353-01   Wnt 7a Protein   15   16        5b   169475673   Wnt 7a protein   17   18           (insert assembly of           NOV5a)        6a   CG50221-01   Apical Endosomal   19   20               Glycoprotein        6b   174308633   Apical Endosomal   N/A   N/A           (insert assembly of   Glycoprotein           NOV6a)        7a   CG50367-01   ADAM13   21   22        7b   CG50367-02   ADAM13   23   24        7c   CG50367-03   ADAM13   25   26        8   CG50321-01   Leucine Rich Containing F   27   28               Box        9   CG55902-01   Steroid Binding   29   30       10a   CG50307-01   Steroid Dehydrogenase   31   32       10b   CG50307-02   Steroid Dehydrogenase   33   34       11   CG50311-01   Myosin Heavy Chain   35   36       12a   CG50323-01   Pancreatitis-Associated   37   38               Protein               (PAP)       12b   169475472   PAP   N/A   N/A           (insert assembly of           NOV12a)       12c   169475476   PAP   N/A   N/A           (Insert assembly of           NOV12a)                  
 
       [0027] 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.  
       [0028] The present invention is based in part on nucleic acids encoding proteins that are novel members of the following protein families: Stabilin/Fascilin/CD-44 precursor FELL-like, Polydom, Transmembrane/IIIb, Serine Protease, Wnt-7a, Apical endosomal glycoprotein, ADAM13, Leucine-rich containing F-Box, Pancreatitis-Associated, Steroid Binding, Steroid dehydrogenase, and Myosin Heavy-chain-like proteins. More particularly, the invention relates to nucleic acids encoding novel polypeptides, as well as vectors, host cells, antibodies, and recombinant methods for producing these nucleic acids and polypeptides.  
       [0029] NOV1 is homologous to the Stabilin family of proteins. Thus, the NOV1 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, for example, cancer, particularly mechanisms of angiogenesis, inflammation, CNS disorders, metabolic disorders including obesity and diabetes and/or other pathologies/disorders.  
       [0030] Fascilin domain-containing proteins have been shown to be important for cell adhesion, which impacts a variety of diseases including cancer, inflammation, obesity and CNS disorders. Stabilin-1 is an endothelial-macrophage member of the fascilin domain containing protein family associated with angiogenesis.  
       [0031] NOV2 is homologous to the Polydom family of proteins. Thus NOV2 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, for example, inflammatory diseases, disorders of coagulation, cancer, obesity, diabetes, asthma, arthritis, osteoporosis, cardiovascular disease and/or other pathologies/disorders.  
       [0032] The mouse polydom protein appears to be important for the regulation of hematopoiesis and may play a role in cell adhesion or in the immune system. Domains within this protein and the human ortholog have been shown to be important in coagulation, growth, cell division, and other important cellular processes.  
       [0033] NOV3 is homologous to a transmembrane/IIIb protein. Thus, the NOV3 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, for example, cancer, trauma, regeneration (in vitro and in vivo), viral/bacterial/parasitic infections, neuroprotection, Von Hippel-Lindau (VHL) syndrome, Alzheimer&#39;s disease, stroke, tuberous sclerosis, hypercalceimia, Parkinson&#39;s disease, Huntington&#39;s disease, cerebral palsy, epilepsy, Lesch-Nyhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, and/or other pathologies/disorders.  
       [0034] The human transmembrane protein described herein has homology to a mouse protein that causes growth inhibition of  E. coli  when expressed exogenously. Therefore, the disclosed transmembrane/IIIb protein of this invention will fulfill a similar function in humans.  
       [0035] NOV4 is homologous to a Serine protease family of proteins. Thus, NOV4 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, for example, cancer, trauma, regeneration (in vitro and in vivo), viral/bacterial/parasitic infections, infertility, and/or other pathologies/disorders.  
       [0036] Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Over 20 families of serine protease have been identified and although they have different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C clans have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base. The geometric orientations of the catalytic residues are similar between families, despite different protein folds. The trypsin family is almost totally confined to animals, although trypsin-like enzymes are found in actinomycetes of the genera Streptomyces and Saccharopolyspora, and in the fungus  Fusarium oxysporum.  The enzymes are inherently secreted, being synthesised with a signal peptide that targets them to the secretory pathway. Animal enzymes are either secreted directly, packaged into vesicles for regulated secretion, or are retained in leukocyte granules.  
       [0037] The NOV4 nucleic acid and polypeptide described in this application has a structure similar to TESP-1 and TESP-2; serine proteases isolated from mouse sperm acrosome. These enzymes are secreted as zymogens and released by the acrosome reaction induced by the calcium ionophore; A23187. These may play a role in fertilization and/or processing of other proteins during fertilization.  
       [0038] NOV5 is homologous to the Wnt-7a protein family. Thus NOV5 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, for example, atherosclerosis, aneurysm, hypertension, fibromuscular dysplasia, stroke, scleroderma, obesity, transplantation disorders, myocardial infarction, embolism, cardiovascular disorders, bypass surgery, endometriosis, infertility, polycystic ovary syndrome, Von Hippel-Lindau (VHL) syndrome, Alzheimer&#39;s disease, tuberous sclerosis, hypercalceimia, Parkinson&#39;s disease, Huntington&#39;s disease, cerebral palsy, epilepsy, Lesch-Nyhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, neurodegeneration, cancer, psoriasis, actinic keratosis, acne, hair growth/loss, allopecia, pigmentation disorders, endocrine disorders, pancreatitis, diabetes, and/or other pathologies/disorders.  
       [0039] Wnt proteins constitute a large family of molecules involved in cell proliferation, cell differentiation and embryonic patterning. They are known to interact with the Frizzled family of receptors to activate two main intracellular signaling pathways regulating intracellular calcium levels and gene transcription. Early studies on Wnts implicated them in cell proliferation and tumorigenesis, which have been borne out by recent work using transgenic and null mutant mice. Wnts are involved in processes involved in mammary gland development and cancer. Recent studies have demonstrated that these molecules are critical to organogenesis of several systems, such as the kidney and brain. Wnts regulate the early development, i.e. neural induction, and their role persists in later stages of development as well as in the mature organ. An example of this is seen in the brain, where the loss of certain Wnts leads to the absence of critical regions of the brain, e.g. the hippocampus, involved in learning and memory, or the cerebellum, involved in motor function. Wnts have also been implicated in the genesis of degenerative diseases such as Alzheimer&#39;s disease.  
       [0040] The NOV5 nucleic acid and polypeptide of the invention has a high degree of similarity to Wnt-7a. Wnt-7a is known to be involved in the development of the limbs, the female reproductive system and the brain. Mutations in Wnt-7a lead to limb patterning defects along with sterility in both males and females. Ectopic expression of this protein leads to inhibition of chondrogenesis. This novel gene may therefore have therapeutic importance in several kinds of developmental defects and cancer, among other pathologis/disorders described above.  
       [0041] NOV6 is homologous to the Apical endosomal glycoprotein family of proteins. Thus NOV6 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, for example, endometriosis, fertility, and/or other pathologies/disorders.  
       [0042] After endocytosis from the plasma membrane, internalized receptors and ligands are delivered to endosomes. The endosomal compartment performs a variety of functions, including the sorting of internalized receptors and ligands, and newly synthesized lysosomal membrane proteins and hydrolases. In polarized epithelial cells, the apical endosomal compartment has been implicated in both apical to basolateral and basolateral to apical transepithelial transport.  
       [0043] NOV7 is homologous to members of the A Disintegrin And Metalloprotease (ADAMs) family of proteins, and specifically domain 13 (ADAM13). Thus, the NOV7 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, for example, Xerostomia, Scleroderma, Hypercalceimia, Ulcers, Von Hippel-Lindau (VHL) syndrome, Cirrhosis,Transplantation, Cirrhosis, Inflammatory bowel disease, Diverticular disease, Hirschsprung&#39;s disease , Crohn&#39;s Disease, Appendicitis, Endometriosis,Fertility, 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, Aneurysm, Fibromuscular dysplasia, Stroke, Bleeding disorders, Hemophilia, hypercoagulation, Idiopathic thrombocytopenic purpura, autoimmume disease,allergies, immunodeficiencies, Graft vesus host, Anemia, Ataxia-telangiectasia, Lymphedema, Allergies, Tonsilitis, and/or other pathologies/disorders.  
       [0044] The ADAM family includes proteins containing disintegrin-like and metalloprotease-like domains. They are also referred to as MDC (Metalloprotease, Disintegrin, Cysteine-rich) proteins. ADAMs are involved in diverse processes such as development, cell-cell interactions and protein ectodomain shedding. In Xenopus, ADAM13 (most closely related to ADAM12) may be involved in neural crest cell adhesion and migration as well as myoblast differentiation. ADAM12/Meltrin α is required for and provokes myogenesis (myoblast fusion).  
       [0045] NOV8 is homologous to the Leucine-rich containing F-Box family of proteins. Since the NOV8 protein of the invention is ubiquitously expressed in many tissues, the NOV8 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in the treatment of patients suffering from diseases associated with these tissues, and/or other pathologies/disorders.  
       [0046] F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 amino acid motif, the F box (so named because cyclin F was one of the first proteins in which this motif was identified). Some F-box proteins have been shown to be critical for the controlled degradation of cellular regulatory proteins. In fact, F-box proteins are one of the four subunits of ubiquitin protein ligases called SCFs. The other three subunits are the Skp1 protein; one of the cullin proteins (Cul1 in metazoans and Cdc53 or Cul A in the yeast  Saccbaromyces cerevisiae ); and the recently identified Roc1 protein (also called Rbx1 or Hrt1). SCF ligases bring ubiquitin conjugating enzymes (either Ubc3 or Ubc4) to substrates that are specifically recruited by the different F-box proteins. The need for high substrate specificity and the large number of known F-box proteins in yeast and worms suggest the existence of a large family of mammalian F-box proteins. There are 26 human F-box proteins. Some of these proteins contain WD-40 domains or leucine-rich repeats; others contain either different protein-protein interaction modules or no recognizable motifs. F-box proteins that contain WD-40 domains Fbws, those containing leucine-rich repeats, Fbls, and the remaining ones Fbxs. The marked differences in F-box gene expression in human tissues suggest their distinct role in ubiquitin-dependent protein degradation.  
       [0047] NOV9 is homologous to a Steroid binding family of proteins. Thus, the NOV9 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, for example, cancer, cataracts, obesity, diabetes, hyperlipidemia, infertility, inflammation, CNS disorders, and/or other pathologies/disorders.  
       [0048] Steroid binding proteins involve reproductive behavior, cell cycle progression and various important physiologic pathologies. Steroid hormones control many normal biological processes but can also cause several disease processes including hormone-dependent cancers of male and female reproductive tissues.  
       [0049] NOV10 is homologous to members of the steroid dehydrogenase family of proteins. Thus, the NOV10 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, for example, 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, adrenoleukodystrophy, congenital adrenal hyperplasia, diabetes, Von Hippel-Lindau (VHL) syndrome, cirrhosis, pancreatitis, endometriosis, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, autoimmume disease, allergies, immunodeficiencies, transplantation, graft versus host disease, osteoporosis, hypercalceimia, arthritis, ankylosing spondylitis, scoliosis, muscular dystrophy, Lesch-Nyhan syndrome, myasthenia gravis, Alzheimer&#39;s disease, stroke, tuberous sclerosis, hypercalceimia, 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, psoriasis, actinic keratosis, acne, hair growth/loss, allopecia, pigmentation disorders, endocrine disorders, and/or other pathologies/disorders.  
       [0050] Steroid dehydrogenase enzymes influence mammalian reproduction, hypertension, neoplasia, and Digestion. The three-dimensional structures of steroid dehydrogenase enzymes reveal the position of the catalytic triad, a possible mechanism of keto-hydroxyl interconversion, a molecular mechanism of inhibition, and the basis for selectivity. Glycyrrhizic acid, the active ingredient in licorice, and its metabolite carbenoxolone are potent inhibitors of human 11 beta-hydroxysteroid dehydrogenase and bacterial 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3 alpha, 20 beta-HSD). The three-dimensional structure of the 3 alpha, 20 beta-HSD carbenoxolone complex unequivocally verifies the postulated active site of the enzyme, shows that inhibition is a result of direct competition with the substrate for binding, and provides a plausible model for the mechanism of inhibition of 11 beta-hydroxysteroid dehydrogenase by carbenoxolone. The structure of the ternary complex of human 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD) with the cofactor NADP+ and the antiestrogen equilin reveals the details of binding of an inhibitor in the active site of the enzyme and the possible roles of various amino acids in the catalytic cleft. The short-chain dehydrogenase reductase (SDR) family includes these steroid dehydrogenase enzymes and more than 60 other proteins from human, mammalian, insect, and bacterial sources. Most members of the family contain the tyrosine and lysine of the catalytic triad in a YxxxK sequence. X-ray crystal structures of 13 members of the family have been completed. When the alpha-carbon backbone of the cofactor binding domains of the structures are superimposed, the conserved residues are at the core of the structure and in the cofactor binding domain, but not in the substrate binding pocket.  
       [0051] Mutations of steroid dehydrogenases have been found to cause various developmental, reproductive or metabolic disorders. For example, Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) give rise to genetic males with female external genitalia. Missense and splice junction mutations severely compromised the activity of the 17 beta-HSD type 3 isozyme and cause male pseudohermaphroditism. Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome. Deficient or impaired 11 beta-hydroxy steroid dehydrogenase in the apparent mineralocorticoid excess syndrome or after licorice ingestion retards the conversion of cortisol to inactive cortisone in the kidney, leading to mineralocorticoid hypertension; this leads to suppression of the renin system and subsequently of aldosterone. In addition, steroid dehydrogenases have been implicated to regulate steroid induced renal reabsorption of sodium. Not only may they control the access of glucocorticoids to MR, but control the access of glucocorticoids to glucocorticoid receptors (GR) as well as access of mineralocorticoids to their own receptors. Finally, steroid dehydrogenases have also been found in neurons and astrocytes, suggesting that these enzymes may be involved in the regulation of brain function. Given their important biological functions, steroid dehydrogenases present excellent small molecule drug targets for therapeutic intervention.  
       [0052] NOV11 is homologous to a Myosin heavy-chain family of proteins. Thus, the NOV11 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be ED useful in therapeutic and diagnostic applications implicated in, for example, restenosis, neurological, glomerular diseases, and/or other pathologies/disorders.  
       [0053] Myosins are molecular motors that upon interaction with actin filaments convert energy from ATP hydrolysis into mechanical force. Evidence has emerged for the existence of a large, widely expressed and evolutionarily ancient superfamily of myosin genes. In addition to the well-catheterized conventional, filament-forming, two-headed myosin-II of muscle and nonmuscle cells, at least ten additional classes of myosins have been identified. In vertebrates, at least seven of the eleven classes are expressed, and many myosins can be expressed in a single cell type. Distance matrix and maximum parsimony methods have been used to study the evolutionary relationships between members of the myosin superfamily of molecular motors. Amino acid sequences of the conserved core of the motor region were used in the analysis. Myosins can be divided into at least three main classes, with two types of unconventional myosin being no more related to each other than they are to conventional myosin. Myosins have traditionally been classified as conventional or unconventional, with many of the unconventional myosin proteins thought to be distributed in a narrow range of organisms. It has been found that members of all three of these main classes are likely to be present in most (or all) eukaryotes. Three proteins do not cluster within the three main groups and may each represent additional classes. The structure of the trees suggests that these ungrouped proteins and some of the subclasses of the main classes are also likely to be widely distributed, implying that most eukaryotic cells contain many different myosin proteins. The groupings derived from phylogenetic analysis of myosin head sequences agree strongly with those based on tail structure, developmental expression, and (where available) enzymology, suggesting that specific head sequences have been tightly coupled to specific tail sequences throughout evolution. Analysis of the relationships within each class has interesting implications. For example, smooth muscle myosin and striated muscle myosin seem to have independently evolved from nonmuscle myosin. Furthermore, brush border myosin I, a type of protein initially thought to be specific to specialized metazoan tissues, probably has relatives that are much more broadly distributed. Myosin II, the conventional two-headed myosin that forms bipolar filaments, is directly involved in regulating cytokinesis, cell motility and cell morphology in nonmuscle cells. To understand the mechanisms by which nonmuscle myosin-II regulates these processes, investigators are looking at the regulation of this molecule in vertebrate nonmuscle cells. The identification of multiple isoforms of nonmuscle myosin-II, whose activities and regulation differ from that of smooth muscle myosin-II, suggests that, in addition to regulatory light chain phosphorylation, other regulatory mechanisms control vertebrate nonmuscle myosin-II activity. It has been shown that nonmuscle myosin II, along with other myosins and cytoskeletal proteins, assembles on Golgi membranes. Nonmuscle myosin II associates transiently with membranes of the trans-Golgi network during the budding of a subpopulation of transport vesicles. The exact role of myosin II in vesicular trafficking is not yet understood, but its participation heralds a novel role for actin-based motors in vesicle budding.  
       [0054] In the aortic wall of mammalian species, the maturation phase of smooth muscle cell (SMC) lineage is characterized by two temporally correlated but opposite regulatory processes of gene expression: upregulation of SM type SM2 myosin isoform and down-regulation of brain (myosin heavy chain B)- and platelet (myosin heavy chain A(pla))-type nonmuscle myosins. There is propensity of the immature type SMC population to be activated in experimental models and human vascular diseases that are characterized by proliferation and migration of medial SMCs into the subendothelial space. Neointimal proliferation leading to restenosis frequently develops after coronary angioplasty. This process is associated with a change in vascular smooth-muscle cells from a contractile (quiescent) phenotype to a synthetic or proliferating (activated) one. The expression of the B isoform of nonmuscle myosin heavy chain is increased in some coronary atherosclerotic plaques and that this increase in expression identifies a group of lesions at high risk for restenosis after atherectomy.  
       [0055] The human homologue of the mouse dilute gene combines elements from both nonmuscle myosin type I and nonmuscle myosin type II. Mutations in the mouse dilute gene result not only in the lightening of coat color, but also in the onset of severe neurological defects shortly after birth, indicating that this gene is important in maintaining the normal neuronal function.  
       [0056] NOV12 is homologous to a Pancreatitis-associated family of proteins. Thus, the NOV12 nucleic acids, polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications implicated in, for example, acute pancreatitis, chronic pancreatitis, and/or other pathologies/disorders.  
       [0057] Human Pancreatitis-associated protein (PAP) is a secretory protein that is strongly expressed in the pancreas with pancreatitis, but not in a healthy pancreas. Thus, synthesis 2.6 increases during inflammation of the pancreas, and a direct relationship between severity of pancreatitis and serum levels of PAP exists. As a result, PAP may be used as a biological marker of acute or chronic pancreatitis.  
       [0058] 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, e.g., neurogenesis, cell differentiation, cell proliferation, hematopoiesis, wound healing and angiogenesis.  
       [0059] Additional utilities for the NOVX nucleic acids and polypeptides according to the invention are disclosed herein.  
       [0060] NOV1  
       [0061] One NOVX protein of the invention, referred to herein as NOV 1, includes stabilin-like proteins. The disclosed proteins have been named NOV1a, NOV1b, and NOV1c.  
       [0062] Stabilin is a member of the fascilin domain containing protein family, which has been shown to be important for cell adhesion. Although such cell adhesion molecules are typically localized at the neuromuscular junction in Drosophila, where they function in the growth and plasticity of the synapse, the protein predicted here is likely to be localized extracellularly in the plasma membrane. Thus, it is likely that the stabilin-like protein of the invention is accessible to a diagnostic probe and for the various therapeutic applications described herein.  
       [0063] The NOV1a protein maps to chromosome 3, whereas the NOV1b protein of the invention maps to chromosome 12. This information was assigned using OMIM, the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0064] NOV1a  
       [0065] In one embodiment, a NOV1 variant is NOV1a (alternatively referred to herein as CG-AC084364.5), which encodes a novel stabilin-like protein and includes the 8444 nucleotide sequence (SEQ ID NO: 1) shown in Table 1A. An open reading frame for the mature protein was identified beginning with an ATG initiation codon at nucleotides 1-3 and ending with a TGA stop codon at nucleotides 8026-8028. Putative untranslated regions downstream from the termination codon are underlined in Table 1A, and the start and stop codons are in bold letters.  
               TABLE 1A                       NOV1a Nucleotide Sequence                                        (SEQ ID NO:1)                           ATG GGCCTGCGCAGTCTGGGGCTCCTGGCTGTGCTGCCACTTCCTGAGTCAAGCACTGGACAGTGTGCAGTGGCC                   AATGCTGGAGGGAGCTGAGCTCTGCAGGAACCCGGCACTGGAAAAAGCCATGTGGGGCTAAGAAACAGAGAAAAG               CTGTTTTTCGGGNNNNNNATGAATGAAATGGAGAGGCAAAGAACTGGAAATAGCAAGACGAGGTATCATGCTACT               GCAATAGTCCAGGCAAAACATGATAAAGGCCTCAACAAGAATGGCACCAGTGGAGATGAAGAGCAGAAGATCAAG               GTGGGAGACAGAGAACAGAGAACAAAGGATTTGATGGCTTATTAGATGTTTGGAAATACTTTAAACTTTATTCAT               CCTTGCTTTGCTGTGTGCAAACTGTGTGCATGGGTGTGCAACAGTGGACTAGATGGCGATGGAACCTGTGAGTGC               TACTCTGCGTACACTGGCCCCAAGTGTGACAAGCTCACAGAAAACTTTCACACCTCTCATCTGACACTGTGGCCT               GTGCACGACTCCAAGCACTGGGGAAGCCTTCGACATCAGAATATGAATGGCACCTGTTCTTCCGGGGGCGGCAAG               GGGGATCCCGATGTTTATCAAAATGGGTTGATTTTCCACGGAGGGGGTACTTCTGGAGGTCTATCGTCATCACGA               AACAGACGAAGTAGTGTCAAGCGTCCTGAGAAGTGGAAGGGGGACGATCGAGATGGAGGTGGCAAGGAAGGCCAG               CAGCGGCGGGCGGGGCAGACACAGAGTCGAGTCTTCAGAGGTCACATCAAAACGCCCCTGCCCCACAGGCAAGGT               GAAGCGCGGATCACGGAGACAACGGGGAATTGTGTTTCTGCTGGCATGACTGGAACCAATGCCAATCACACAAAA               GTTCACCCTACGGTTCAGTCCTTGACAGAATATGATTCCTTTCAGACTCATTCCACCAGCAGACTGAAGGAATTT               GAGAAACAGCAGGTGAAGGAAGATTTTTCTGACCCTCCCCTAATGCAGGCTATAAAACCCTCACATGAGAAGTAC               CCTCCTTATGCCCAGAGATAAGGAACATCTTTGTCTCCAAGACACAGGGACACGGAGATGATGAAACAGGCCTTG               CTAAGTTTCCTCCACTCTATTACCCTTAGCTTGTACCTTTATCCAACCACATTCTTCCATGACTCTCCAGTCTTC               ATCAAACCTGGCATAAACACTCAGACTTAACCACTTCTTTGGGTCTTCATTTCCTTATGTTAAGGCTCCAGTGTC               ATANNNNNNNATGGGAATTGAGGTTTGGAAAACTGGTGCCAAAATGCTGATACCCTGGCTGCTGCCCCTGCTCCA               TCCCTGAATGTGCAGCCTTGCTCTGCCCAGAAAATTCCAGATGTTCGCCTTTCCACTGAAGATGAAAACAACTGG               AATGCAAATGCCTTCCCAATTACCGAGGCGATGGCAATACTGCGACCCCATCAATCCATGTTTACGAAAAAATCT               GCCACCCTCATGCTCATTGTACGTACCTGGGACCAAATCGGCACAGTTGTACATGCCAAGAAGGCTACCGTGGGG               ATGGCCAAGTGTGCTTGCCTGTGGACCCCTGCCAAATTAACTTTGGAAACTGCCCTACAAAGTCTACAGTGTGCA               AATATGATGGGCCTGGACAGATGCATTTGCCAGAAAGGTTACGTGGGTGATGGCTTAACGTGTTATGGAAACATT               ATGGAGCGACTCAGAGAATTAAATACTGAACCCAGAGGAAAATGGCAAGGAAGGCTGACCTCTTTCATCTCACTC               CTAGAAAGTATACAAATTGTAAGTGTACAACTCAGTGAATTTTCCCAACGTGAACCTACTTGTGTAAACACCAAG               TCCATTGCCAGCAACCTAGAAGGCCCCCTGGTCCCCCTTTCCAATCATTACCCTCTACAGGTAAATGAGCTTTTG               GTGGATAATAAAGCTGCTCAATACTTTGAAATGCTCCACATAATTGCTGGTCAGATGAACATCGAATATATGAAT               AACACAGACATGTTCTACACCTTGACTGGAAAGTCGGGGGAAATCTTCAACAGCGATAAGGACAATCAAATAAAG               CTTAAACTCCATGGAGGCAAAAAGAAGGTAAAAATTATACAAGGGGACATCATTGCTTCCAATGGGCTTCTGCAC               ATCCTTGACAGAGCCATGGACAAGTTAGAACCCACATTTGAGAGCAACAATGAGGAAACCAATTTGGGACATGCC               TTAGATGAGGATGGAGTTGGTGGACCATACACCATTTTTGTTCCAAATAATGAAGCATTGAATAACATGAAGGAC               GGCACTCTCGATTACCTCCTTTCTCCAGAQCTTGAAGTGGCCACTCTCATCTCCACCCCTCACATAAGGAGCATG               GCCAACCAGCTCATACAGTTCAACACCACCGACAATGGACAGATTCTGGCAAATGATGTGGCAATGGAAGAAATT               GAGATCACTGCCAAAAATGGCCGAATTTACACACTGACAGGAGTTCTCATTCCTCCCTCCATTGTCCCGATTCTG               CCCCATCGATGTGATGAAACAAGAGAGAGATGAAAACTGGGCACTTGTGTGAGCTGTTCTCTGGTGTACTGGAGC               AGATGTCCTGCTAACTCTGAGCCCACAGCACTCTTCACACACAGATGTGTCTACAGTGGCAGGTTTGGGAGCCTG               AAGAGCGGCTGTGCCCGGTACTGCAATGCCACTGTGAAGTGTGCAGATAGCCTCGGCGGCAACGGGACATGCATT               TGTGAGGAGGGCTTCCAAGGCTCCCAGTGTCAGTTCTGCTCTGATCCCAATAAATACGGACCTCGGTGTAACAAA               AAATGCCTGTGCGTTCACGGAACATGCAATAACAGGATAGACAGCGATGGGGCCTGCCTCACTGGCACATGCAGA               GACGCTCTGCCGGGAGACTCTGTGATAAAGCAGACCTCAGCCTGTGGGCCCTACGTGCAGTTCTGTCAAATCCAC               GCCACCTGTGAATACAGCAATGGGACAGCCAGTTGTATTTGCAAAGCAGGATATGAAGGAGATGGAACTCTGTGT               TCTGAGATGGACCCTTGCACAGGACTAACTCCAGGAGGCTGTAGCCGCAATGCAGAATGCATCAAAACTGGCACG               GGCACCCACACCTGCGTGTGTCAGCAGGGTTGGACAGGGAATGGGAGAGACTGCTCGGAGATCAACAACTGCCTG               CTGCCCAGTGCAGGCGGCTGCCACGACAACGCATCCTGTTTGTATGTGGGTCCCGGGCAGAATGAGTGTGAGTGC               AAGAAAGGATTTCGAGGAAATGGGATTGACTGTGAACCAATAACTTCATGCTTGGAACAAACCGGGAAATGTCAT               CCATTGGCAAGCTGTCAATCTACTTCGTCTGGTGTCTGGAGCTGTGTTTGTCAAGAGGGCTATGAAGGAGATGGC               TTTCTGTGCTATGGAAACGCAGCAGTGGAATTGTCATTTCTCTCCGAAGCAGCTATATTTAACCGATGGATAAAT               AATGCTTCTCTACAACCCACACTGTCAGCCACCTCAAACCTCACTGTCCTCGTGCCTTCCCAACAAGCTACTGAG               GACATGGACCAGGATGAGAAAAAGCTTCTGGTTGTCACAGAGCAATATTCCAGCCCTAATAAGTACCATATGCTA               CTAGGCACATACAGAGTGGCAGATCTGCAGACCCTGTCTTCTTCTGACATGTTGGCAACATCTTTGCAGGGCAAC               TTCCTTCACTTGGCAAAGGTGGATGGGAATATCACAATTGAAGGGGGCCTCCATTGTCGATGGGGACAACGAGCC               ACAAATGGAGTGATACACATCATCAACAAGGTGCTGGTCCCACAAAGACGTCTAACTGGCTCCTTACCAAACCTG               CTCATGCGGCTGGAACAGATGCCTGACTATTCCATCTTCCGGGGCTACATCATTCAATATAATCTGGCGAATGCA               ATTGAGGCTGCCGATGCCTACACAGTGTTTGCTCCAAACAACAATGCCATCGAGAATTACATCAGGGAGAAGAAA               GTCTTGTCTCTAGAGGAGGACGTCCTCCGGTATCATGTGGTCCTGGAGGAGAAACTCCTGAAAAGAATGACCTGC               AATGGCATGCATCGTGAGACCATGCTGGGTTTCTCCTATTTCCTTAGCTTCTTTCTCCATAATGACCAGCTCTAT               GTAAATGAGGCTCCAATAACTACACCAAATGTAGCCACTGATAAGGGAGTGATCCATGGTTTGGGAAAAGTTCTG               GAAATTCAGAAGAACAGATGTGATAATAATGACACTACTATTATACGAGGAAGATGTAGGACATGCTCCTCAGAG               CTGACCTGCCCATTCGGAACTAAATCTCTAGGTAATGAGAAGAGGAGATGCATCTATACCTCCTATTTCATGGGA               AGACGAACCCTGTTTATTGGGTGCCAGCCAAAATGTGTGAGAACCGTCATTACGAGAGAATGCTGTGCCGGCTTC               TTTGGCCCCCAATGCCAGCCCTGTCCAGGGAATGCCCAGAATGTCTGCTTTGGTAATGGCATCTGTTTGGATGGA               GTGAATGGCACAGGTGTGTGTGAGTGTGGGGAGGGCTTCAGCGGCACAGCCTGCGAGACCTGCACCGAGGGCAAG               TACGGCATCCACTGTGACCAGCATGTTCTTGTGTCCATGGGAGATGAACCAAGGACCCTTGGGAGATGGCTCTCC               TGTGACTGTGATGTTGGCTGGCGAGGAGTGCATTGTGACAATGCAACCACAGAAGACAACTGCAATGGGACATGC               CATACCAGCGCCAACTGCCTCACCAACTCAGATGGTACAGCTTCATGCAAGTGTGCAGAAGGATTCCAAGGAAAC               GGQACCATCTGCACAGCAATCAATGCCTGTGAGATCAGCAATGGAGGTTGCTCTGCCAAGGCTGACTGTAAGAGA               ACCACCCCAGGAAGGCGAGTGTGCACGTGCAAAGCAGGCTACACGGGTGATGGAATTGTGTGCCTGGAAATCAAC               CCGTGTTTGGAGAACCATGGTGGCTGTGACAAGAATGCGGAGTGCACACAGACAGGACCCAACCAGGCTGCCTGT               AACTGTTTGCCAGCATACACTGGAGATGGAAAGGTCTGCACACTCATCAATGTCTGCTTAACTAAAAATGGCGGC               TGTGGTGAATTTGCCATCTGCAACCACACTGGGCAAGTAGAAAGGACTTGTACTTGCAAGCCAAACTACATTGGA               GATGGATTTACCTGCCGCGGCAGCATTTATCAGGAGCTTCCCAAGAACCCGAAAACTTCCCAGTATTTCTTCCAG               TTGCAGGAGCATTTCGTGAAAGATCTGGTCGGCCCAGGCCCCTTCACTGTTTTTGCACCTTTATCTGCAGCCTTT               GATGAGGAAGCTCGGGTTAAAGACTGGGACAAATACGGTTTAATGCCCCAGGTTCTTCGGTACCATGTGGTCGCC               TGCCACCAGCTGCTTCTGGAAACCTGAAATTGATCTCAAAATGCTACTTCCCTCCAAGGAGAGCCAATAGTCATC               TCCGTCTCTCAGAGCAACGGTGTATATAATAATAAGGCTAAGATCATATCCAGTGATATCATCAGTACTAATGGG               ATTGTTCATATCATAGACAAATTGCTATCTCCCAAAAATTTGCTTATCACTCCCAAAGACAACTCTGGAAGAATT               CTGCAAAATCTTACGACTTTGGCAACAAAACAATGGCTACATCAAATTTAGCAACTTAATACAGGACTCAGGTTTG               CTGAGTGTCATCACCGATCCCATCCACACCCCAGTCACTCTCTTCTGGCCCACCGACCAAGCCCTCCATGCCCTA               CCTGCTGACAACAGGACTTCCTGTTCAACCAAGACAACAAGGACAAGCTGAAGGAGTATTTGAAGTTTCATGTG               ATACGAGATGCCAAAGGTTTTAGCTGTGGATCTTCCCACATCCACTGCCTGGAAGACCCTGCAAGGTTCAGAGCTG               AGTGTGAATGTGGAGCTGGCAGGGACATCGGTGACCTCTTTCTGAATGGCCAAACCTGCAGATTTGTGCAGCGG               GAGCTCTTGTTTGACCTGGGTGTGGCCTACGGCATTGACTGTCTGCTGATTGATCCCACCCTGGGGGGCCGCTGT               GACACCTTTACTACTTTCGATGCCTCGGGGGAGTGTGGGAGCTGTGTCAATACTCCCAGCTGCCCAAGGTGGAGT               AAACCAAAGGGTGTGAAGCAGAAGTGTCTCTACAACCTGCCCTTCAAGAGGAACCTGGAAGGCTQCCGGGAGCGG               TGCAGCCTGGTGATACAGATCCCCAGGTGCTQCAAQGGCTACTTCGGGCGAGACTGTCAGGCCTGCCCTGGAGGA               CCAGATGCCCCGTGTAATAACCGGGGTGTCTGCCTTGATCAGTACTCGGCCACCGGAGAGTGTAAATGCAACACC               GGCTTCAATGGGACGGCGTGTGAGATGTGCTGGCCGGGGAGATTTGGGCCTGATTGTCTGCCCTGTGGCTGCTCA               GACCACGGACAGTGCGATGATGGCATCACGGQCTCCGGGCAGTGCCTCTGTGAAACGGGGTGGACAGGCCCCTCG               TGTGACACTCAGGCAQTTTTGCCTGCAGTGTGTACGCCTCCTTGTTCTGCTCATGCCACCTGTAAGGAGAACAAC               ACGTGTGAGTGTAACCTGGATTATGAAGGTGACGGATCACATGCACAGTTGTGGAATTTCTGCAACAGQACAAC               GGGGGCTGTGCAAAGGTGGCCAGATGCTCCCAGAAGGGCACGAAGGTCTCCTGCAGCTGCCAGAAGGGATACAAA               GGGGACGGGCACAGCTGCACAGAGATAGACCCCTGTGCAGACGGCCTTAACGGAGGGTGTCACGAGCACGCCACC               TGTAAGATGACAGGCCCGGGCAAGCACAAGTGTGAGTGTAAAAGTCACTATGTCGGAGATGGGCTGAACTGTGAG               CCGGAGCAGCTGCCCATTGACCGCTGCTTACAGGACAATGGGCAGTGCCATGCAGACGCCAAATGTGTCGACCTC               CACTTCCAGGATACCACTGTTGGGGTGTTCCATCTACGCTCCCCACTGGGCCAGTATAAGCTGACCTTTGACAAA               GCCAGAGAGGCCTGTGCCAACGAAGCTGCGACCATGGCAACCTACAACCAGCTCTCCTATGCCCAGAAGGCCAAG               TACCACCTGTGCTCAQCAGGCTGGCTGGAGACCGGGCGGGTTGCCTACCCCACAGCCTTCGCCTCCCAGAACTGT               GGCTCTGGTGTGGTTGGGATAGTGGACTATGQACCTAGACCCAACA1AAGAGTGAAATGTGGGATGTCTTCTGCTAT               CGGATGAAAGGAAGTGCTGGCCTATTCCAACAGCTCAGCTCGAGGCCGTGCATTTCTAGAACACCTGACTGACCTG               TCCATCCGCGGCACCCTCTTTGTGCCACAGAACAGTGGGCTGGGGGAGAATGAGACCTTGTCTGGGCGGGACATC               GAGCACCACCTCGCCAATGTCAGCATGTTTTTCTACAATGACCTTGTCAATGGCACCACCCTGCAAACGAGGCTG               GGAAGCAAGCTGCTCATCACTGCCAGCCAGGACCCACTCCAACCGGTACAAAAGTAGGTTTGTTGATCGAAGAGCC               ATTCTGCAGTGGGACATCTTTGCCTCCAATGGGATCATTCATGTCATTTCCAGGCCTTTAAAAGCACCCCCTGCC               CCCGTGACCTTGACCCACACTGGCTTGGGAGCAGGGATCTTCTTTTGCATCATCCTGGTGACTGGGGCTCTTGCC               TTGGCTGCTTACTCCTACTTTCGGATAAACCGGAGAACAATCGGCTACCAGCATTTTGAGTCGGAAGAGGACATT               AATGTTGCAGCTCTTGGCAAGCAGCAGCCTGAGAAATATCTCGAACCCCTTGTATGAGAGCACAACCTCAGCTCCC               CCAGAACCTTCCTACGACCCCTTCACGGACTCTGAAGAAACQGCAGCTTGAGGGCAATGACCCCTTGAGACACTG                 TGA   GGGCCTGGACGGGAGATGCCAGCCATCACTCACTGCCACCTGGGCCATCAAACTGTGAATTCTCAGCACCAGT                   TGCCTTTTAGGAACGTAAAGTCCTTTAAGCACTCAGAAGCCATACCTCATCTCTCTGGCTGATCTGGGGGTTGTT                   TCTGTGGGTGAGAGATGTGTTGCTGTGCCCACCCAGTACAGCTTCCTCCTCTGACCCTTTGGCTCTTCTTCCTTT                   GTACTCTTCAGCTGGCACCTGCTCCATTCTGCCCTACATGATGGGTAACTGTGATCTTTCTTCCCTGTTAGATTG                   TAAGCCTCCGTCTTTGTATCCCAGCCCCTAGCCCAGTGCCTGACACAGGAACTGTGCACAATAAAGGTTTATGGA                   ACAGAAACAAAGTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA                    
 
       [0066] The sequence of NOV1a was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0067] The DNA sequence and protein sequence for a novel stabilin-like gene were obtained by SeqCallingTM Technology and are reported here as NOV1a. These methods used to amplify NOV1a cDNA are described in Example 2.  
       [0068] The NOV1a polypeptide (SEQ ID NO: 2) encoded by SEQ ID NO: 1 is 2675 amino acid residues in length and is presented using the one-letter amino acid code in Table 1B. The SignalP, Psort and/or Hydropathy results predict that NOV1a has a signal peptide and is likely to be localized extracellularly in the plasma membrane with a certainty of 0.6760. In alternative embodiments, a NOV1a polypeptide is located to the endoplasmic reticulum (membrane) with a certainty of 0.1000, the endoplasmic reticulum (lumen) with a certainty of 0.1000, or outside the cell with a certainty of 0.1000. The SignalP predicts a likely cleavage site for a NOV1a peptide between amino acid positions 20 and 21, i.e. at the dash in the sequence STG-QC.  
               TABLE 1B                       Encoded NOVia Protein Sequence                                        (SEQ ID NO:2)                         MGLRSLGLLAVLPLPESSTGQCAVAICCWRELSSAGTRHWRNHVGLRNREKLFFGXXMNEMERQETGNSKTRYHAT                   AIVQAHDKGLNKAAGTSGDEEQKIKVGDRDRENKGFDGLLDWNTLNFIHPCFAVCNCVHGVCNSGLDGDGTCEC               YSAYTGPKCDKLTENFHTSHLTWPVHDSKHWGSLRHQNMNGTCSSGGGKDGPDVYQNGLIFHGGGTSGGLSSSR               NRRSSVKRPEKWKGDDRDGGGKEGQQRRPAADTESSLQRGHIKTPLPHRQGEAAITETTGNCVSAGMTGAAAATK               VHPTVQSLTEYDSFQTHSTSRLKEFEKQQVKERFSDPPLMQAIKPSHEKYPPYAQRKGTSLSPKTQGHGDDEQAL               LSFLHSITLSLYLYPTTFFHDSPVFIKPGIKTLRLAAFFGSSFPYECSSVIXXMGIEAAAACQNADTLAAAPAP               SLNVQPCSAQKIPDVRLPLKMKTNWNANAFPITEAMANTATPSIHVYEKSATLMLIVRTWDQIGTVVHAKKATVG               MAKCACLWTPAKLTLETALQSLQCANAAGLDRCICQKGYVGDGLTCYGNIMERLRELNTEPRGKWQGRLTSFISL               LESIQIVSVQLSEFSQREPTCVNTKSIASNLEGPLVPLSHNYPLQVNELLVDNKAAQYFVKLIHIIAGQMNIEYMN               NTDMFYTLTGKSGEIFNSDKDNQIYAAKLHGGKKKVKIIQGDIIASNGLLHILDRAMDKLEPTFESNNEETNLGAA               LDEDGVGGPYTIFVPNNEALNNMKDGTLDYLLSPELEVATLISTPHIRSMANQLIOFNTTDNGQILANDVAMEEI               EITAKNGRIYTLTGVLIPPSIVPILPHRCDETKREMKLGTCVSCSLVYWSRCPANSEPTALFTHRCVYSGRFGSL               KSGCARYCNATVKCADSLGGNGTCICEEGFQGSQCQFCSDPNKYGPRCNKKCLCVHGTCNNRIDSDGACLTGTCR               DGSAGRLCDKQTSACGPYVQFCHIAATCEYSNGTASCICKAGYEGDGTLCSEMDPCTGLTPGGCSPAANAECIKTGT               GTHTCVCQQGWTGNGRDCSEINNCLLPSAGGCHDNASCLYVGPGQNECECKKGFRGNGIDCEPITSCLEQTGKCH               PLASCQSTSSGVWSCVCQEGYEGDGFLCYGNAAVELSFLSEAAIFNRWINNASLQPTLSATSNLTVLPSQQATE               DMDQDEKSFWLSOSNIPALIKYHMLLGTYRVADLQTLSSSDMLATSLQGNFLHLAKVDGNITIEGASIVDGDNAA               TNGVIHIINKVLVPQRRLTGSLPNLLMRLEQMPDYSIFRGYIIQYNLANAIEAADAYTVFAPNNNAIENYIREKK               VLSLEEDVLRYHVVLEEKLLKNDLHNGMHRETMLGFSYFLSFFLHNDQLYVNEAPINTYNVATDKGVIHGLGKVL               EIQKNRCDNNDTTIIRGRCRTCSSELTCPFGTKSLGNEKRRCIYTSYFMGRRTLFIGCQPKCVRTVITRECCAGF               FGPQCQPCPGNAQNVCFGNGICLDGVNGTGVCECGEGFSGTACETCTEGKYGIHCDQACSCVHGRCNQGPLGDGS               CDCDVGWRGVHCDNATTEDNCNGTCHTSANCLTNSDGTASCKCAAGFQGNGTICTAINACEISNGGCSAKADCKR               TTPGRRVCTCKAGYTGDGIVCLEINPCLENHGGCDKNAECTQTGPNQAACNCLPAYTGDKVCTLINVCLTKNGG               CGEFAICNHTGQVERTCTCKPNYIGDGFTCRGSTYQELPKNPKTSQYFFQLQEHFVLVGPGPFTVFAPLSAAF               DEEARVKDWDKYGLMPQVLRYIZACHQLLLENLAAISNATSLQGEPIVISVSQSTAAIAAAATSSDIISTNG               IVHIIDKLLSPKNLLITPKDDNSGRILQNLTTLATNNGYIKFSNLIQDSGLLSVITDPIHTPVTLFWPTDQALHAL               PAEQQDFLNQDNKDKLKEYLKFHVIRDAKVLAVDLPTSTAWKTLQGSSELSVKCGAGRDIGDLFLNGQTCRIVQR               ELLFDLGVAYGIDCLLIDPTLGGRCDTFTTFDASGECGSCVNTPSCPRWSKPKGVKQKCLYNLPFKRNLEGCRER               CSLVIQIPRCCKGYFGRDCQACPGGPDAPCAAGVCLDQYSATGECKCNTGAAGTACEMCWPGRFGPDCLPCGCS               DHGQCDDGITGSGQCLCETGWTGPSCDTQAVLPAVCTPPCSAHATCKENNTCECNLDYEGDGITCTVVDFCKQDN               GGCAKVARCSQKGTKVSCSCQKGYKGDGHSCTEIDPCADGLNGGCHEHATCKMTGPGKHKCECKSHYVGDGLNCE               PEQLPIDRCLQDNGQCHADAKCVDLHFQDTTVGVFHLRSFLGQYKLTFDKAREACANEAATMATYNQLSYAQKAK               YHLCSAGWLETGRVAYPTAFASQNCGSGVVGIVDYGPRPNKSEMWDVFCYRMKEVLAYSNSSARGRAFLEHLTDL               SIRGTLFVPQNSGLGENETLSGRDIEHHLANVSMFFYNDLVNGTTLQTRLGSKLLITASQDPLQPVQSRFVDGRA               ILQWDIFASNGIIHVISRPLKAPPAPVTLTHTGLGAGIFFCIILVTGAVALAAYSYFRINPRTIGYQHFESEEDI               NVAALGKQQPENISNPLYESTTSAPPEPSYDPFTDSEERQLEGNDPLRTL                  
 
       [0069] NOV1b  
       [0070] In an alternative embodiment, a NOV1 variant is NOV1b (alternatively referred to herein as CG50736-10), which includes the 8495 nucleotide sequence (SEQ ID NO: 3) shown in Table 1C. An open reading frame for the mature protein was identified beginning at nucleotides 201-203 and ending at nucleotides 7461-7463. The start and stop codons of the open reading frame are highlighted in bold type. Putative untranslated regions, found upstream from the initiation codon and downstream from the termination codon, are underlined.  
               TABLE 1C                       NOV1b Nucleotide Sequence                                        (SEQ ID NO:3)                           AAATCATCCCACATGCTAAGAATCTAAGATGTATAAAATAAAGTGGTAGAAAGATGAAAATGAAATTTTATCAAG                       GTTAGAGTCAGGTTGGAGTGGCCATTGTTTACCACTGAGAAATCTAAATTTTATTTGGTTGGTAATTGAGA                   GTCATTGAGATATTTTGGGGAAGGTCACCCTGATGCCTTTGCTAATCAAATGAA   ATG AATGAAATGGAGAGGC               AAGAAACTGGAAATAGCAAGACGAGGTATCATGCTACTGCAATAGTCCAGGCAAAACATGATAAAGGCCTCAA               CAAGAATGGCACCAGTGGAGATGAAGAGCAGAAGATCAAGGTCGGACCACAGAGACAGAGAAAAACAAAGGATTT               GATGGCTTATTAGATGTTTGGAATACTTTAAACTTTATTCATCCTTGCTTTGCTGTGTGCAACTGTGTGCATG               GGGTGTGCAACAGTGGACTAGATGGCGATGGAACCTGTGAGTGCTACTCTGCGTACACTGGCCCCAAGTGTGA               CAAGCTCACAGAAAAACTTTCACACCTCTCATCTGACACTGTGGCCTGTGCACGACTCCAAGCACTGGGGAAGC               CTTCGACATCAGAATATGAATGGCACCTGTTCTTCCGGGGGCGGCAAGGGGGATCCCGATGTTTATCAAAATG               GGTTGATTTTCCACGGAGGGGGTACTTCTGGAGGTCTATCGTCATCACGAAACAGACGAACTACTGTCAAAACCG               TCCTGAGAAGTGGAAGGGGGACGATCGAGATGGAGGTGGCAAGGAAGGCCAGCAGCGGCGGCGGGCAGACACA               GAGTCGAGTCTTCAAGAGGTCACATCAACGCCCCTGCCCCACAGGCAAAGGTGAAGCGCGGATCACGGAGA               CAACGGGGAATTGTGTTTCTGCTGGCATGACTGGAACCAATGCCAATCACACAAAAGTTCACCCTACGGTTCA               GTCCTTGACAGAATATGATTCCTTTCAGACTCATTCCACCAGCAGACTGAAGGAAATTTGAGAACAGCAAGGTG               AAGGAAAGATTTTCTGACCCTCCCCTAATGCAGGCTATAAAAACCCTCACATGAGAAGTACCCTCCTTATGCCC               AGAGAAAAGGAACATCTTTGTCTCCAAAGACACAGGGACACGGAGATGATGAACAGGCCTTGCTAAGTTTCCT               CCACTCTATTACCCTTAGCTTGTACCTTTATCCAAACCACATTCTTCCATGACTCTCCAGTCTTCATCAAACCT               GGCATAAAAACACTCAGACTTAACCACTTCTTTGGGTCTTCATTTCCTTATGAAGGCTCCAGTGTCATAANAA               NNATGGGAATTGAGGTTTGGAAAAACTGGTGCCAAAATGCTGATACCCTGGCTGCTGCCCCTGCTCCATCCCT               GAATGTGCAGCCTTGCTCTGCCCAGAAAATTCCAGATGTTCGCCTTCCACTGAAGATGAAAACAAACTGGAAT               GCAAAATGCCTTCCCAATTACCGAGGCGATGGCAAATACTGCGACCCCATCAATCCATGTTTACGAAAAATCTG               CCAACCCTGATGCTCATTGTACGTACCTGGGACCAAATCGGCACAGTTGTACATGCCAAGAAGGCTACCGTGGG               GATGGCCAAGTGTGCTTGCCTGTGGACCCCCTGCCAAATTAACTTTGGAAACTGCCCTACAAAGTCTACAGTGT               GCAAATATGATGGGCCTGGACAGATGCATTTGCCAGAAAGGGTTACGTGGGTGATGGCTTAACGTGTTATGGAA               ACATTATGGAGCGACTCAGAGAATTAAATACTGAACCCAGAGGAAAAATGGCAAGGAAGGCTGACCTCTTTCAT               CTCACTCCTAGAAAGTATACAAATTGTAAGTGTACAACTCAGTGAATTTTTCCCAACGTGAACCTACTTGTGTA               AACACCAAGTCCATTGCCAGCAACCTAGAAGGCCCCCCTGGTCCCCCTTTCCAATCATTACCCTCTACAGGTAA               ATGAGCTTTTTGGTGGATAATAAGCTGCAATCAATACTTTGTGAACTCCACATAATTGCTGGTCAGATGAACAT               CGAATATATGAATAACACAGACATGTTCTACACCTTGACTGGAAAGTCGGGGGGAAATCTTCAACAGCGATAAG               GACAATCAAATAAAGCTTAAACTCCATGGAGGCAAAAAGAAGGTAAAAATTATACAAGGGGACATCATTGCTT               CCAATGGGCTTCTGCACATCCTTGACAGAGCCATGGACAAGTTAGAACCCACATTTGAGAGCAACAATGAGGA               AACCAATTTGGGACATGCCTTAATGAGGATGGAGTTGGTGGACCATACACCATTTTTGTTCCAAATAATGAAA               GCATTGAATAACATGAAGGACGGCACTCTCGATTACCTCCTTTCTCCAGAGCTTGAAGTGGCCACTCTCATCT               CCACCCCTCACATCAGGAGCATGGCCAACCAGCTCATACAGTTCAACACCACCGACAATGGACAGATTCTGGC               AATGATGTGGCAATGGAAGAAATTGAGATCACTGCCAAAAATGCCGAAGAATTACACACTGACAGGAGTTCTC               GTGTGAGCTGTTCTCTGGTGTACTGGAGCAGATGTCCTGCTAACTCTGAGCCCACAGCACTCTTCACACACAG               GTGTGAGCTGTTCTCTGGTGTACTGGAGCAGATGTCCTGCTAACTCTGAGCCCACAGCACTCTTCACACACAG               ATGTGTCTACAGTGGCAGGTTTGGGAGCCTGAAGAGCGGCTGTGCCCGGTACTGCAATGCCACTGTGAAGTGT               GCAGATAGCCTCGGCGGCAACGGGACATGCATTTGTGAGGAGGGCTTCCAAGGCTCCCAGTGTCAGTTCTGCT               CTGATCCCAATAAATACGGACCTCGGTGTAACAAAAAATGCCTGTGCGTTCACGGAACATGCAATAACAGGAT               AGACAGCGATGGGGCCTGCCTCACTGGCACATGCAGAGACGGCTCTGCCGGGAGACTCTGTGATAAGCAGACC               TCAGCCTGTGGGCCCTACGTGCAGTTCTGTCACATCCACGCCACCTGTGAATACAGCAATGGGACAGCCAGTT               GTATTTGCAAGCAGGATATGAAGGAGATGGAACTCTGTGTTCTGAGATGGACCCTTGCACAGGACTAAACTCC               AGGAGGCTGTAGCCGCAATGCAGAATGCATCAAAACTGGCACGGGCACCCACACCTGCGTGTGTCAGCAGGGT               TGGACAGGGAATGGCAGAGACTGCTCGGAGATCAACAACTGCCTGCTGCCCAGTGCAGGCGGCTGCCACGACA               ACGCATCCTGTTTGTATGTGGGTCCCGGGCAGAATGAGTGTGAGTGCAAGAAGGATTTCGAGGAAAATGGGAT               TGACTGTGAACCAATAACTTCATGCTTGGAACAAACCGGGAAATGTCATCCATTGGCAAGCTGTCAATCTACT               TCGTCTGGTGTCTGGAGCTGTGTTTGTCAAGAGGGCTATGAAGGAGATGGCTTTCTGTGCTATGGAAACGCAG               CAGTGGAATTGTCATTTCTCTCCGAAGCAGCTATATTTAACCGATGGATAAATAATGCTTCTCTACAACCCAC               ACTGTCAGCCACCTCAAACCTCACTGTCCTCGTGCCTTCCCAACAAGCTACTGAGGACATGGACCAGGATGAG               AAAAGCTTCTGGTTGTCACAGAGCAATATTCCAGCCCTAATAAAGTACCATATGCTACTAGGCACATACAGAG               TGGCAGATCTGCAGACCCTGTCTTCTTCTGACATGTTGGCAACATCTTTGCAGGGCAACTTCCTTCACTTGGC               AAAGGTGGATGCGAATATCACAAATTGAAGGGGCCTCCATTGTCGATGGGGACAACGCAGCCACAATGGAGTG               ATACACATCATCAACAAGGTGCTGGTCCCACAAAGACGTCTAACTGGCTCCTTACCAAACCTCCTCATGCGGC               TGGAACAGATGCCTGACTATTCCATCTTCCGGGGCTACATCATTCAATATAATCTGGCGAATGCAATTGAGGC               TGCCGATGCCTACACAGTGTTTGCTCCACAACAATGCCATCGAGAATTACATCAGGGAGAAGAAAAAGTCTTG               TCTCTAGAGGAGGACGTCCTCCGGTATCATGTGGTCCTGGAAGGAAGCTCCTGAAGAATGACCTGCAACAATG               GCATGCATCGTGAGACCATGCTGGGTTTCTCCTATTTCCTTAGCTTCTTTCTCCATAATGACCAGCTCTATGT               AAATGAGGCTCCAATAAACTACACCAATGTAGCCACTGATAAGGGAGTGATCCATGGTTTGGGAAAAGTTCTG               GAATTCAGAAGAACAGATGTGATAATAATGACACTACTATTATACGAGGAAAGATGTAGGACATGCTCCTAAG               AGCTGACCTGCCCATTCGGAACTAAATCTCTAGGTAATGAGAAGAGGAGATGCATCTATACCTCCTATTTCAT               GGGAAGACGAACCCTGTTTATTGGGTGCCAGCCAAAATGTGTGAGAACCGTCATTACGAGAGAATGCTGTGCC               GGCTTCTTTGGCCCCCAATGCCAGCCCTGCCCAGGGAATGCCCAGAATGTCTGCTTTGGTAATGGCATCTGTT               TGGATGGAGTGAATGGCACAGGTGTGTGTGAGTGTGGGGAGGGCTTCAGCGGCACAGCCTGCGAGACCTGAAC               CGAGGGCAAGTACGGCATCCACTGTGACCAAGCATGTTCTTGTGTCCATGGGAGATGC1ACCAAGGACCCTTG               GGAGATGGCTCCTGTGACTGTGATGTTGGCTGGCGAGGAGTGCATTGTGACAATGCAACCACAGAAGACAACT               GCAATGGGACATGCCATACCAGCGCCAACTGCCTCACCAACTCAGATGGTACAGCTTCATGCAAGTGTGCAGC               AGGATTCCAAGGAACGGGACCATCTGCACAGCAATCAATGCCTGTGAGATCAGCAAATGGAGGTTGCTCTGCC               AAGGCTGACTGTAAGAGAACCACCCCAGGAAGGCGAGTGTGCACGTGCAAAGCAGGCTACACGGGTGATGGCA               TTGTGTGCCTGGAATCAACCCGTGTTTGGAGACCATGGTGGCTGTGACAAGAAATGCGGAGTGCACACAGAC               AGGACCCACCAGGCTGCCTGTAAACTGTTTGCCAGCATACACTGGAGATGGAAGGTCTGCACACTCATCAAT               GTCTGCTTAACTAAAATGGCGGCTGTAGTGAATTTGCCATCTGCAACCACACTGGGCAAGTAGAAAGGACTT               GTACTTGCAAGCCAACTACATTGGAGATGGATTTACCTGCCGCGGCAGCATTTATCAGGAGCTTCCCAAGAA               CCCGAAAACTTCCCAGTATTTCTTCCAGTTGCAGGAGCATTTCGTGAAGATCTGGTCGGCCCAGGCCCCTTC               ACTGTTTTTGCACCTTTATCTGCAGCCTTTGATGAGGAAGCTCGGGTTAAGACTGGGACAATACGGTTTAAAA               TGCCCCAGGTTCTTCGGTACCATGTGGTCGCCTGCCACCAGCTGCTTCTGGAAAACCTGAAATTGATCTCAA               TGCTACTTCCCTCCAAGGAGAGCCAATAGTCATCTCCGTCTCTCAGAGCACGGTGTATATAACAATAAGGCT               AAGATCATATCCAGTGATATCATCAGTACTAATGGGATTGTTCATATCATAGACAAATTGCTATCTCCCAAAA               ATTTGCTTATCACTCCCAAAGACAACTCTGGAAGAATTCTGCAAAATCTTACGACTTTGGCAACAAACAATGG               CTACATCAAATTTAGCAACTTAATACAGGACTCAGGTTTGCTGAGTGTCATCACCGATCCCATCCACACCCCA               GTCACTCTCTTCTGGCCCACCGACCAAGCCTCCATGCCCTCCATGCCCTACCTGCTGAACAAACAGGACTTCC               TGTTCAACCAAGACAACAAGGACAAGCTGAAGGAGTATTTGAAGTTTCATGTGATACGAGATGCCAAGGTTTT               AGCTGTGGATCTTCCCACATCCACTGCCTGGAAGACCCTGCAAGGTTCAGAGCTGAGTGTGAAATGTGGAGCT               GGCAGGGACATCCGTGACCTCTTTCTGAATGGCCAAAQCTACAGAATTGTGCAGCGGGAGCTCTTGTTTGACC               TGGGTGTGGCCTACGGCATTGACTGTCTGCTGATTGATCCCACCCTGGGGGGCCGCTGTGACACCTTTACTAC               TTTCGATGCCTCGGGGGAGTGTGGGAGCTGTGTCAATACTCCCAGCTGCCCAGGTGGAGTAAACCAAAGGGGT               GTGAAGCAGAAGTGTCTCTACAACCTGCCTTCAAGAGGAACCTGGAAGGCTGCCCGGGAGCGGTGCAGCCTGG               TTATACAGATCCCCAGGTGCTGCAAGGGCTACTTCGGGCGAGACTGTCAGGCCTGCCCTGGAGGACCAGATGC               CCCGTGTAATAACCGGGGGTGTCTGCCTTGATCAGTACTCGGCCACCGGAGAGTGTAATGCAACACCGGCTTC               AATGGGACGGCGTGTGAGATGTGCTGGCCGGGGAGATTTGGGCCTGATTGTCTGCCCTGTGGCTGCTCAGACC               ACGGACAGTGCGATGATGGCATCACGGGCTCCGGGCAGTGCCTCTGTGAACGGGGTGGACAGGCCCCCTCGTG               TGACACTCAGGCAQTTTTGCCTGCAGTGTGTACGCCTCCTTGTTCTGCTCATGCCACCTGTAAGGAGAACAAC               ACGTGTGAGTGTAACCTGGATTATGAAGGTGACGGAATCACATGCACAGTTGTGGATTTCTGCAAACAGGACA               ACGGGGGCTGTGCAAAGGTGGCCAGATGCTCCCAGAAGGGCACGAAGGTCTCCTGCAGCTGCCAGAAGGGATA               CAAAGGGGACGGGCACAGCTGCACGAGATAGACCCCTGTGCAGACGGCCTTAAACGGAGGGTGTCACGAGCAC               GCCACCTGTAAGATGACAGGCCCGGGCAAGCACAAGTGTGAGTGTAAAAGTCACTATGTCGGAGATGGGCTGA               ACTGTGAGCCGGAGCAGCTGCCCATTGACCGCTGCTTACAGGACAATGGGCAGTGCCATGCAGACCCAAAATG               TGTCGACCTCCACTTCCAGGATACCACTGTTGGGGTGTTCAATCTACGCTCCCAACTGGGCCAGTATAAGCTG               ACCTTTGACAAAGCCAGAGAGGCCTGTGCCAACGAAGCTGCGACAATGGCAACCTACAACCAGCTCTCCTATG               CCCAGAAGGCCAAGTACCACCTGTGCTCAGCAGGCTGGCTGGAGACCGGGCGGGTTGCCTACCCCACAGCCTT               CGCCTCCCAGAACTGTGGCTCTGGTGTGGTTGGGATAGTGGACTATGGACCTAGACCCAACAAGAGTGAAATG               TGGGATGTCTTCTGCTATCGGATGAAGGAAGTGCTGGCCTATTCCAACAGCTCAGCTCGAGGCCGGTGCATTT               CTAGAACACCTGAC TGA   CCTGTCCATCCGCGGCACCCTCTTTGTGCCACAGAACAGTGGGCTGGGGGAGAATG                   AGACCTTGTCTGGGCGGGACATCGAGCACCACCTCGCCAATGTCAGCATGTTTTTTCTAAATGACCTTGTCAA                   TGGCACCACCCTGCAAACGAGGCTGGGAAGCAAAGCTGCTCATCACTGCCAGCCAGGACCCACTCCAACCGACG                   GAGACCAGGTTTGTTGATGGAAGAGCCATTCTGCAGTGGGACATCTTTGCCTCCAATGGGATCATTCATGTCA                   TTTCCAGGCCTTTAAAAGCACCCCCTGCCCCCGTGACCTTGACCCACACTGGCTTGGGAGGAAGGGATCTTC                   TGCCATCATCCTGGTGACTGGGGCTGTTGCCTTGGCTGCTTACTCCTACTTTCGGATAAACCGGAGAACAA                   GGCTTCCAGCATTTTGAGTCGGAAGAGGACATTAATGTTGCAGCTCTTGGCAAGCAGCAGCCTGAGAATATCT                   CGAACCCCTTGTATGAGAGCACAACCTCAGCTCCCCCAGAACCTTCCTACGACCCCTTCACGGACTCTGAAG                   ACGGCAGCTTGAGGGCAATGACCCCTTGAGGACACTGTGAGGGCCTGGACGGGAGATGCAAGCCATCACTCAC                   TGCCACCTGGGCCATCAACTGTGAATTCTCAGCACCAGTTGCCTTTTAGGAACGTAAAGTCCTTTAAGCACTC                   AGAAGCCATACCTCATCTCTCTGGCTGATCTGGGGGTTGTTTCTGTGGGTGAGAGATGTGTTGCTGTGCCCCAC                   CCAGTACAGCTTCCTCCTCTGACCCTTTGGCTCTTCTTCCTTTGTACTCTTCAGCTGGCACCTGCTCCATTCT                   GCCCTACATGATGGGTAACTGTGATCTTTCTTCCCTGTTAGATTGTAAGCCTCCGTGTCTTGTATCCCAGCCCC                   TAGCCCAGTGCCTGACACAGGAACTGTGCACAATAAAGGTTTATGGAACAGAAACAAAGTCAAAAAAAAAAAAA                   AAAAAAAAAAAAAAAAAAAAAAAAAC                    
 
       [0071] The sequence of NOV1b was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0072] The DNA sequence and protein sequence for a novel stabilin-like gene were obtained by SeqCallingTM Technology and are reported here as NOV1b. These methods used to amplify NOV1b cDNA are described in Example 2.  
       [0073] The NOV1b polypeptide (SEQ ID NO: 4) encoded by SEQ ID NO: 3 is 2420 amino acid residues in length and is presented using the one-letter amino acid code in Table 1D. The SignalP, Psort and/or Hydropathy results predict that NOV1b has no known signal peptide and is likely to be localized in the cytoplasm with a certainty of 0.4500. In alternative embodiments, a NOV1b polypeptide is located to the microbody (peroxisome) with a certainty of 0.3000, the mitochondrial matrix space with a certainty of 0.1000, or the lysosome (lumen) with a certainty of 0.1000.  
               TABLE 1D                       Encoded NOV1b Protein Sequence                                        (SEQ ID NO:4)                         MNEMERQETGNSKTRYHATAIVQAKHDKGLNKNGTSGDEEQKIKVGDRDRENKGFDGLLDVWNTLNFIHPCFAV                   CNCVHGVCNSGLDGDGTCECYSAYTGPKCDKLTENFHTSHLTLWPVHDSKHWGSLRHQNAAGTCSSGGGKGDPD               VYQNGLIFHGGGTSGGLSSSRNRRSSVKRPEKWKGDDRDGGGKEGQQRRRADTESSLQRGHIKTPLPHRQGEAA               ITETTGNCVSAGMTGTNANAHTKVHPTVQSLTEYDSFQTHSTSRLKEFEKQQVKERFSDPPLMQAIKPSHEKYPP               YAQRKGTSLSPKTQGHGDDEQAALSFLHSITLSLYLYPTTFFHDSPVFIKPGIKTLRLAAFFGSSFPYEGSSVI               XXMGIEVWKNWCQNADTLAAAPAPSLNVQPCSAQKIPDVRLPLKMKTNWNANAFPITEAMANTATPSIHVYEKS               ATLMLIVRTWDQIGTVVHAKKATVGMAKCACLWTPAKLTETALQSLQCANMMGLDRCICQKGYVGDGLTCYGN               IMERLRELNTEPRGKWQGRLTSFISLLESIQIVSVQLSEFSQREPTCVNTKSIASNLEGPLVPLSNHYPLQVNE               LLVDNKAAQYFVKLHIIAGQMNIEYMNNTDMFYTLTGKSGEIFNSDKDNQIKLKLHGGKKKVKIIQGDIIASNG               LLHILDRAMDKLEPTFESNNEETNLGHALDEDGVGGPYTIFVPNNEALNNMKDGTLDYLLSPELEVATLISTPH               IRSMANQLIQFNTTDNGQILDVAAEEIEITAAAGRIYTLTGAALIPPSIVPILPHRCDETKREMKAAGTCVSCS               LVYWSRCPANSEPTALFTHRCVYSGRFGSLKSGCARYCNATVKCADSLGGNGTCICEEGFQGSQCQFCSDPNKY               GPRCNKKCLCVHGTCNNRIDSDGACLTGTCRDGSAGRLCDKQTSACGPYVQFCHIHATCEYSNGTASCICKAGY               EGDGTLCSEMDPCTGLTPGGCSRNAECIKTGTGTHTCVCQQGWTGNGRDCSEINNCLLPSAGGCHDNASCLYVG               PGQNECECKKGFRGNGIDCEPITSCLEQTGKCHPLASCQSTSSGVWSCVCQEGYEGDGFLCYGNAAVELSFLSE               AAIFNRWINNASLQPTLSATSNLTVLVPSQQATEDMDQDEKSFWLSQSNIPALIKYHMLLGTYRVADLQTLSSS               DMLATSLQGNFLHLAKVDGNITIEGASIVDGDNAATNGVIHIINKVLVPQRRLTGSLPNLMRLEGMPDYSIFR               GYTIQYNLANAIEAADAYTVFAPNNNAIENYTREKVLSLEEDVLRYVLEEAALAALAAGAARETMLGPSY               FLSFFLHDQLYNEAPINYTNATDKGVIHGLGAALEIQAACDAADTTIIRGRCRTCSSELTCPFGTKSLGN               EKRRCIYTSYFMGRRTLFIGCQPKCAAAATTRECCAGFFGPQCQPCPGNAQAACFGNGICLDGAAGTGVCECG               GFSGTACETCTEGKYGThCDQACSCAAGRCNQGPLGDGSCDCDVGWRGAACDNATTEDNCNGTCHTSAACLTNS               DGTASCKCAAGFQGNGTICTAINACEISNGGCSAKADCKRTTPGRRVCTCKJAAGYTGDGIVCLEINPCLEAAGGC               DKNAECTQTGPNQAACNCLPAYTGDGKVCTLINVCLTKNGGCSEFAICNHTGQVERTCTCKPNYIGDGFTCRGS               IYQELPKNPKTSQYFFQLQEHFVKDLVGPGPFTVFAPLSAAFDEEARVKDWDKYGLMPQVLRYHVVACHQLLLE               NLKLISNATSLQGEPIVISVSQSTVYINNKAKIISSDIISTNGIVHIIDKLLSPKNLLITPKDNSGRILQNLTT               LATNNGYIKFSNLIQDSGLLSVITDPIHTPVTLFWPTDQALHALHALPAEQQDFLFNQDNKDKLKEYLKFHVIR               DAKVLAVDLPTSTAWKTLQGSELSVKCGAGPAAIGDLFLNCQTYRIVQRELLFDLGVAYGIDCLLIDPTLGRCD               TFTTFDASGECGSCVNTPSCPRWSKPKGVKQKCLYNLPFKRNLEGCRERCSLVIQIPRCCKGFGRDCQACPGG               PDAPCNNRGVCLDQYSATGECKCNTGFNGTACEMCWPGRFGPDCLPCGCSDHGQCDDGITGSGQCLCETGWTG               SCDTQAVLPAVCTPPCSAHATCKENNTCECNLDYEGDGITCTVVDFCKQDNGGCAKVARCSQKGTKVSCSCQKG               YKGDGHSCTEIDPCADGLNGGCHEHATCKMTGPGKHKCECKSHYVGDGLNCEPEQLPIDRCLQDNGQCHADAKC               VDLHFQDTTVGVFHLRSPLGQYKLTFDKAREACANEAATMATYNQLSYAQKAKYHLCSAGWLETGRVAYPTAFA               SQNCGSGVVGIVDYGPRPNKSEMWDVFCYRMKGSAGLFQQLSSRPCISRTPD                  
 
       [0074] NOV1c  
       [0075] A NOV1 variant includes NOV1c (alternatively referred to as CG 50736-09), which includes the 3260 nucleotide sequence (SEQ ID NO: 210) shown in Table 1E.  
               TABLE 1E                       NOV1C NuCleotide Sequence                                        (SEQ ID NO:210)                         GGCACGAGCAGGAGCTTCCCAAGAACCCGAAAAACTTCCCAGTATTTCTTCCAGTTGCAGGAGCATTTCGTGAA                   AGATCTGGTCGGCCCAGGCCCCCTTCACTGTTTTTGCACCTTTATCTGCAGCCTTTGATGAGGAAGCTCGGGTT               AAAGACTGGGACAAATACGGTTTAATGCCCCAGGTTCTTCGGTACCATGTGGTCGCCTGCCACCAGCTGCTTC               TGGAAACCTGAATTGATCTCAATGCTACTTCCCTCCAAGGAGAGCCAAAAAATAGTCATCTCCGTCTCTCAGAG               CACGGGTGTATATAAATAATAAGGCTAAGATCATATCCAGTGATATCATCAGTACTAATGGGATTGTTCATATC               ATAGACAAATTGCTATCTCCCAAAATTTGCTTATCACTCCCAAAGACAACTCTGGAAGAATTCTGCAAAATC               TTACGACTTTGGCAACAAACAATGGCTACATCAAATTTAGAACTTAATACAGGACTCAGGTTTGCTGAGTGT               CATCACCGATCCCATCCACACCCCAGTCACTCTCTTCTGGCCCACCGACCAAGCCCTCCATGCCCTACCTGCT               GAACAACAGGACTTCCTGTTCAACCAAGACAACAAGGACAAGCTGAAGGAGTATTTGAAGTTTCATGTGATAC               GAGATGCCAAGGTTTTAGCTGTGGATCTTCCCACATCCACTGCCTGGAAGACCCTGCAAGGTTCAGAGCTGAG               TGTGAATGTGGAGCTGGCAGGGACATCGGTGACCTCTTTCTGAATGGCCAACCTGCAGAATTGTGCAGCAGG               GAGCTCTTGTTTGACCTGGGTGTGGCCTACGGCATTGACTGTCTGCTGATTGATCCCACCCTGGGGGGCCGCT               GTGACACCTTTACTACTTTCGATGCCTCGGGGGAGTGTGGGAGCTGTGTCAATACTCCCAGCTGCCCAAGGTG               GAGTAAACCAAAGGGTGTGAAGCAGAAGTGTCTCTACAACCTGCCCTTCAAGAGGAACCTGGAAGGCTGCCGG               GAGCGGTGCAGCCTGGTGATACAGATCCCAAGGTGCTGCAAGGGCTACTTCGGGCGAGACTGTCAGGCCTGCC               CTGGAGGACCAGATGCCCCGTGTAATAACCGGGGTGTCTGCCTTGATCAGTACTCGGCCACCGGAGAGTGTAA               ATGCAACACCGGCTTCAAATGGGACGGCGTGTGAGATGTGCTGGCCGGGGAGATTCGGGCCTGATTGTCTGCCC               TGTGGCTGCTCAGACCACGGACAGTGCGATGATGGCATCACGGGCTCCGGGCAGTGCCTCTGTGAAAACGGGGT               GGACAGGCCCCCTCGTGTGACACTCAGGCAGTTTTGCCTGCAGTGTGTACGCCTCCTTGTTCTGCTCATGCCAC               CTGTAAGGAGAACAACACGTGTGAGTGTAACCTGGATTATGAAGGTGACGGGAATCACATGCACAGTTGTGGAT               TTCTGCAAACAGGACAACGGGGGGCTGTGCAAAGGTGGCCAGATGCTCCCAGAAGGGCACGAAGGTCTCCTGCA               GCTGCCAGAAGGGATACAAAAGGGGACGGGCACAGCTGCACAGAGATAGACCCCTGTGCAGACGGCCTTAACGG               AGGGTGTCACGAGCACGCCACCTGTAAGATGACAGGCCCGGGGCAAGCACAAGTGTGAGTGTAAAAGTCACTAT               GTCGGAGATGGGCTGAACTGTGAGCCGGAGAAGCTGCCCCATTGACCGCTGCTTACAGGACAATGGGCAGTGCC               ATGCAGACGCCAAAATGTGTCGACCTCCACTTCCAGGATACCACTGTTGGGGTGTTCCATCTACGCTCCCCACT               GGGCCAGTATAGCTGACCTTTGACAAGCCAGGAGAGGCCTGTGCAACAACGAAGCTGCGACCATGGCAACCTAC               AACCAGCTCTCCTATGCCCAGAAAAGGCCAAGTACCACCTGTGCTCAGCAGGCTGGCTGGAGACCGGGCGGTTG               CCTACCCCACAGCCTTCGCCTCCCAGAACTGTGGCTCTGGTGTGGTTGGGATAGTGGACTATGGACCTAGACC               CAACAAGAGTGAAATGTGGGATGTCTTCTGCTATCGGATGAAAGATGTGAACTGCACCTGCAAGGTGGGCTAT               GTGGGAGATGGCTTCTCATGCAGTGGGAAACCTGCTGCAGGTCCTGATGTCCTTCCCCTCACTAACAACTTCC               TGACGGAAGTGCTGGCCTATTCCAACAGCTCAGCTCGAGGCCGTGCATTTCTAGAACACCTGACTGACCTG               CATCCGCGGCACCCTCTTTGTGCCACAGAACAGTGGGCTGGGGGAGAATGAGACCTTGTCTGGGCGGGACATC               GAGCACCACCTCGCCAATGTCAGCATGTTTTTCTACAATGACCTTGTCAATGGCACCACCCTGCAACGAGGG               TGGGAAGCAGCTGCTCATCCTGCCAGCCAGGACCCACTCCAACCGACGGAGACCAGGTTTGTTGATGGAAG               AGCCATTCTGCAGTGGGACATCTTTGCCTCCAATGGGATCATTCATGTCATTTCCAGGCCTTTAAAAGCACC               CCTGCCCCCGTGACCTTGACCCACACTGGCTTGGGAGCAGGGATCTTCTTTGCCATCATCCTGGTGACT               CTGTTGCCTTGGCTGCTTACTCCTACTTTCGGATCCGGAGAACAATCGGCTTCCAGCATTTTGAGTCGGA               AGAGGACATTAATGTTGCAGCTCTTGGCAAGCAGCAGCCTGAGAATATCTCGAACCCCTTGTATGAGAGCACA               ACCTCAGCTCCCCCAGAACCTTCCTACGACCCCTTCACGGACTCTGAAGAAACGGCAGCTTGAGGGCAATGACC               CCTTGAGGACACTGTGAGGGCCTGGACGGGAGATGCAAGCCATCACTCACTGCCACCTGGGCCATCAACTG               AATTCTCAGCACCAGTTGCCTTTTAGGAAJAACGTGTCCTTTAAGCACTCAGAAGCCATACCTCATCTCTG               GCTGATCTGGGGGTTGTTTCTGTGGGTGAGAGATGTGTTGCTGTGCCCACCCAGTACAGCTTCCCTCTGAC               CCTTTGGCTCTTCTTCCTTTGTACTCTTCAGCTGGCACCTGCTCCATTCTGCCCTACATGATGGGTAAGTG               ATCTTTCTTCCCTGTTAGATTGTAAGCCTCCNTCTTTGTATCCCAGCCCCTAGCCCAGTGCCTGACAGGAA               CTGTGCACAAATAGGTTTATGGAACAGAAAAAAAAAAAAAAAAA                  
 
       [0076] The NOV1c polypeptide (SEQ ID NO: 211) encoded by SEQ ID NO: 210 is 897 amino acid residues in length and is presented using the one letter amino acid code in Table 1F.  
               TABLE 1F                       Encoded NOV1C Protein Sequence                                        (SEQ ID NO:211)                         MPQVLRYHVVACHQLLLENLKLISNATSLQGEPIVISVSQSTVYINNKAKIISSDIISTNGIVHIIDKLLSPKN                   LLITPKDNSGRILQNLTTLATNNGYIKFSAAIQDSGLLSVITDPIHTPVTLFWPTDQALAALPAAQQDFLFNQD               NKDKLKEYLKFHVIRDAKVLAVDLPTSTAWKTLQGSELSVKCGAGRDIGDLFLNGQTCRIVQRELLFDLGVAYG               IDCLLIDPTLGGRCDTFTTFDASGECGSCVNTPSCPRWSKPKGVKQKCLAALPFAANLEGCRERCSLVIQIPRC               CKGYFGRDCQACPGGPDAPCNNRGVCLDQYSATGECKCNTGFNGTACEMCWPGRFGPDCLPCGCSDHGQCDDGI               TGSGQCLCETGWTGPSCDTQAVLPAVCTPPCSAHATCKENNTCECNLDYEGDGITCTVVDFCKQDNGGCAKVAR               CSQKGTKVSCSCQKGYKGDGHSCTEIDPCADGLNGGCHEHATCKMTGPGKHKCECKSHYVGDGLNCEPEQLPID               RCLQDNGQCHADAKCVDLHFQDTTVGVFHLRSPLGQYKLTFDKAREACANEAATMATYNQLSYAQKAKYHLCSA               GWLETGRVAYPTAFASQNCGSGVVGIVDYGPRPNKSEMWDVFCYAACTCKAAJGAAAAGDGFSCSGNLLQVLMS               FPSLTNFLTEVLAYSNSSARGRAFLEHLTDLSIRGTLFVPQAASGLGENETLSGPLIEHHAAVSMFFYAALAAG               TTLQTRVGSKLLITASQDPLQPTETRFVDGRAILQWDIFASNGIIHVISRPLKAPPAPVTLTHTGLGAGIFFAI               ILVTGAVALAAYSYFRINRRTIGFQHFESEEDINVAALGKQQPENISNPLYESTTSAPPEPSYDPFTDSEERQL               EGNDPLRTL                  
 
       [0077] Searches of the sequence databases revealed that NOV1c has 99% homolgy to a CD44-like precursor FELL-like protein. Included in the invention are variants of the parent clone NOV1c as shown below in Table 1G. These novel variants were derived by laboratory cloning of cDNA fragments coding for a domain of the full length form of NOV1c (CG50736-09), between residues 85 and 636 (Fascilin domain). The cDNA coding for the variant sequences was cloned by the polymerase chain reaction (PCR). Primers were designed based on in silico predictions of the full length or some portion (one or more exons) of the cDNA/protein sequence of the invention, or by translated homology of the predicted exons to closely related human sequences or to sequences from other species. These primers and methods used to amplify the variant cDNA are described in Example 2.  
               TABLE 1G                          Variants of NOV1c                             Nov1c                   Variant   Alternate   Change in SEQ ID   Change in SEQ       No.   Reference   NO: 210   ID NO: 211               1   169487446   T → C at bp 887; and   Q → L at aa 325               A → T at bp 1144;       2   169487460   C → T at bp 1034; and   No change               T → C at bp 1244;       3   169487473   C → T at bp 1223;   N → Y at aa 416; and               A → T at bp 1416; and   C → R at aa 487               T → C at bp 1629       4   169487491   G → A at bp 1534; and   S → N at aa 455               A → G at bp 1547;       5   169487497   A → G at bp 976; and   K → R at aa 269; and               G → A at bp 2010;   G → S at aa 614       6   169487533   A → G at bp 832;   Y → C at aa 221               C → T at bp 1223; and               T → C at bp 2003       7   169487538   A → G at bp 513; and   I → V at aa 115; and               T → C at bp 1888;   M → T at aa 573       8   169487577   G → T at bp 712   No change                  
 
       [0078] SNP variants of NOV1 are disclosed in Example 3.  
       [0079] NOV1 Clones  
       [0080] Unless specifically addressed as NOV1a, NOV1b, NOV1c, or variants of NOV1c, any to NOV1 is assumed to encompass all variants.  
       [0081] The amino acid sequnce of NOV1 has high homology to other proteins as shown in Table 1H  
               TABLE 1H                          BLASTX Results from Patp Database for NOV1                                 Smallest           High   Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P (N)                                     patp: AAY93910   A human hyaluronan-binding   2493    1.2e−290           protein, designated WF-HABP       patp: AAY93913   A human hyaluronan-binding   848   1.9e−157           protein, designated BM-HABP       patp: AAB42164   Human ORFX 0RF1928   1017    1.9e−138           polypeptide sequence       patp: AAY93911   A human hyaluronan-binding   536   6.1e−75            protein, designated WF-HABP       patp: AAR05222   Antigen GX5401FL encoded by   353   4.3e−54            Eimeria tenella genomic DNA                  
 
       [0082] In a search of sequence databases, it was found, for example, that the NOV1a nucleic acid sequence has 1593 of 2797 bases (56%) identical to a gb:GENBANK-ID:HSA275213|acc:AJ275213.1 mRNA from  Homo sapiens  ( Homo sapiens  mRNA for stabilin-1 (Stab1 gene)). Further, the full amino acid sequence of the disclosed NOV1a protein of the invention has 543 of 1391 amino acid residues (39%) identical to, and 760 of 1391 amino acid residues (54%) similar to, the 2570 amino acid residue ptnr:SPTREMBL-ACC:Q9NY15 protein from  Homo sapiens  (Human) (STABILIN-1).  
       [0083] In a similar search of sequence databses, it was found, for example, that the NOV1b nucleic acid sequence has 2654 of 2678 bases (99%) identical to a gb:GENBANK-ID:HSM801377|acc:AL133021.1 mRNA from  Homo sapiens  ( Homo sapiens  mRNA; cDNA DKFZp434E0321 (from clone DKFZp434E0321)). Further, the full amino acid sequence of the disclosed NOV1b protein of the invention has 638 of 642 amino acid residues (99%) identical to, and 638 of 642 amino acid residues (99%) similar to, the 897 amino acid residue ptnr:SPTREMBL-ACC:Q9NRY3 protein from  Homo sapiens  (Human) (CD44-LIKE PRECURSOR FELL).  
       [0084] Additional BLASTP results are shown in Table 1I.  
               TABLE 11                          NOV1 BLASTP Results                                     Gene Index/       Length of                   Identifier   Protein/Organism   aa   Identity (%)   Positives (%)   Expect Value                                             Q9UF98   HYPOTHETICAL 115.7   1069   1038/1064   1042/1064   0.0           KDA PROTEIN -  Homo         (97%)   (97%)              sapiens  (Human)       Q9H7H7   FLJ00112 PROTEIN -   1192   926/929    928/929    0.0             Homo sapiens  (Human)       (99%)   (99%)        Q9NRY3   CD44-LIKE PRECURSOR   897   640/641    641/641    0.0           FELL -  Homo sapiens         (99%)   (100%)           (Human)       Q9NY15   STABILIN-1 -  Homo     2570   543/1391   760/1391   0.0             sapiens  (Human)       (39%)   (54%)        Q93072   MYELOBLAST   2212   614/1740   897/1740   0.0           KIAA0246 PROTEIN —       (35%)   (51%)              Homo sapiens  (Human)                  
 
       [0085] A multiple sequence alignment is given in Table 1J, with the NOV1a and NOV1b proteins of the invention being shown in lines 1 and 2 , in a ClustalW analysis comparing NOV1 with related protein sequences of Table 1I. 
 
 
 
 
 
 
 
 
 
       [0086] Domain results for NOV1 were collected from the Pfam database, and then identified by the InterPro domain accession number. The results are listed in Table 1K with the statistics and domain description. These results indicatee that the NOV1 polypeptides have properties similar to those of other proteins known to contain these domains.  
                   TABLE 1K                          Domain Analysis of NOV1                                     Score   E           PSSMs Producing Significant Alignments   (bits)   Value                                 FasCiclin; domain 3 of 4, from 1756 to 1886   53.1   6.3e−12                                     Fasciclin   agtvmeklktdprfstlvaaleaadLvetlnnsgdfTVFAPTNdAFq   (SEQ ID NO:44)                +++   +  ++ +|    +++   +++++ +++++|||||  +||+       NOV1a   RGSIYQElPKNPKTSQYFFQlQEH-FVKDlVGPGPFTVFAPlSAAFD   (SEQ ID NO:2)                   klpagdlktldeLlnkedakqLakILtYH.Vvagklstadllslstpvlt             +++   +++  +         ++| || |+ +++   ++   ++   +       NOV1a   E-EAR---VKDWDKY----GLMPQVLRYHvVACHQLLLENLKLLSN--AT                   slqGskitvsgkndtellkdvnvlkVnnatvivesDiettNGviHViDrV           +++|+++ ++++  +        +  ++ + ++++|+ ++||++|++|++       NOV1a   SLQGEPIVISVSQST--------VYINNKAKIISSDIISTNGIVHIIDKL                   LlP           | |       NOV1a   LSP                                         Fasciclin: domain 4 of 4, from 1900 to 2043   41.9   1.5e−08                                     Fasciclin   agtvmekiktdprtStlvaaleaadLvetlnnsg..dfTVFAPTNdA   (SEQ ID NO:45)                    +++++++   +++ +++ ++|+++ +++ ++++|+| ||+ |       NOV1a   ILQNLTTLATNNGYIKFSNLIQDSGLLSVITDPIhtPVTlFWPTDQA   (SEQ ID NO: 2)                   FqkLpagdlktldeLlnkedakqLakILtYHVvagklstadllslstpvl           + +|+++    ++ |++++++++|++ |++||+ + ++ +  +++++       NOV1a   LHAlPAE---QQDFLFNQDNKDKLKEYLKFHVIRDAKVLAVDLPTSTA-W                   tslqGskitvsgkndtellkdvnvlkVnnat.vivesDiettNGviHViD           ++++|+++++++  ++    ++  +  ++ + +++ +    + |+ + +|       NOV1a   KTLQGSELSVKCGAGR----DIGDLFLNGQTCRIVQRELLFDLGVAYGID                   rVLlP            +|       NOV1a   CLLID                                         Xlink: domain 1 of 1, from 2358 to 2450   100.8   4.1e−43                                     Xlink   GeVFhyrapsgRYkltFeEAqaaCirqgAriATtgQlyAAwkgafdq   (SEQ ID NO:46)                +||+++++ + |+++|+ |+++|+++ |+ ||+ ||  | ++ ++       NOV1a   -GVFHLRSPLGQYKLTFDKAREACANEAATMATYNQLSYAQKAKYHL   (SEQ ID NO:2)                   CdAGWLADgsVRYPIvkPRenCgGdkdgfpGVRtyYlfpNQTGfpddpss           |+||||  ++| ||   ++++|+ +     |+ ++       | + ++++       NOV1a   CSAGWLETGRVAYPTAFASQNCGSGV---VGIVDY-------GPRPNKSE                   rYDvYCF           +|++|+       NOV1a   MWDVFCY                  
 
       [0087] The NOV1 proteins disclosed in this invention is expressed in at least the following tissues: 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 and uterus. This information was derived by determining the tissue sources of the sequences that were included in the invention including but not limited to SeqCalling sources, Public EST sources, Literature sources, and/or RACE sources.  
       [0088] The protein similarity information, expression pattern, cellular localization, and map location for the NOV1 proteins and nucleic acids disclosed herein suggest that this Stabilin-like protein may have important structural and/or physiological functions characteristic of the Stabilin and/or epidermal growth factor (EGF) families. Therefore, the nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications. For example, the compositions of the present invention will have efficacy for treatment of patients suffering from: heart diseases (particularly mechanisms of angiogenesis), cancers such as, for example, erythroid-megakaryocytic leukaemia, breast cancer, fibrosarcoma, neoplasia, such as T-cell acute lymphoblastic leukemia/lymphoma and mammary carcinomas, chronic contact dermatitis, familial and congenital cholestatic diseases, Hereditary vascular dementia, neurological diseases, CNS disorders, autoimmune disease, inflammation, immunodeficiencies, systemic lupus erythematosus, metabolic disorders (obesity and/or diabetes), asthma, emphysema, scleroderma, allergies, and other diseases, disorders and conditions of the like.  
       [0089] The novel nucleic acid encoding the Stabilin/Fascilin-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV1 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV1 epitope is from about amino acids 45 to 125. In another embodiment, a contemplated NOV1 epitope is from about amino acids 200 to 375. In other specific embodiments, contemplated NOV1 epitopes are from about amino acids 400 to 2700.  
       [0090] NOV2  
       [0091] Another NOVX protein of the invention, referred to herein as NOV2, includes two novel polydom-like proteins. The disclosed proteins have been named NOV2a and NOV2b. Polydom-like proteins are important for the regulation of hematopoiesis and may play a role in cell adhesion or in the immune system. Domains within this protein have been shown to be important in coagulation, growth, cell division, and other important cellular processes.  
       [0092] Although some members of the polydom-like protein family may be localized in the lysosome, the protein predicted here is similar to the mouse polydom protein which is localized extracellularly. Therefore, it is likely that this polydom-like protein is available at the same localization, and hence accessible to a diagnostic probe, and for the various therapeutic applications described herein.  
       [0093] The NOV2a and NOV2b proteins disclosed in this invention map to chromosome 9. This information was assigned using OMIM, the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0094] NOV2a  
       [0095] In one embodiment, a NOV2 variant is NOV2a (alternatively referred to herein as CG142106342), which encodes a novel polydom-like protein and includes the 11158 nucleotide sequence (SEQ ID NO: 5) shown in Table 2A. An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 77-79 and ending with a TAA codon at nucleotides 10787-10789. Putative untranslated regions downstream from the termination codon and upstream from the initiation codon are underlined in Table 2A, and the start and stop codons are in bold letters.  
               TABLE 2A                       NOV2a Nucleotide Sequence                                        (SEQ ID NO:5)                           CAATTGGTCTAGGGTCTCCCCCATTGGAATATCCATCAGTGATGAGAATACAACGTTTGTTGAGTTTTCTCTAGC                       ATG AGAAGAATTTGCGCGGCTTGCTGGGGTCTGGCGCTCGTTTCGGGCTGGGCGACCTTTCAGCAGATGTCCCCGT               CGCGCAATTTCAGCTTCCGCCTCTTCCCCGAGACCGCGCCCGGGGCCCCCGGGAGTATCCCCGCGCCGCCCGCTCC               TGGCGACGAAGCGGCGGGGAGCAGAGTGGAGCGGCTGGGCCAGGCGTTCCGCGTGCGGCTGCTGCGGGAGCTCAGC               GAGCGCCTGGAGCTTGTCTTCCTGGTGGATGATTCGTCCAGCGTGGGCGAAGTCAACTTCCGCAQCGAGCTCATGT               TCGTCCGCAAGCTGCTGTCCGACTTCCCCGTGGTGCCCACGGCCACGCGCGTGGCCATCGTGACCTTCTCGTCCAA               GACTACGTGGTGCCGCCGTCGATTACATCTCCACCCGCCGCGCGCGCAAGCACAAAAGTGCGCGCTGCTCCTCCAA               GAGATCCCTGCCATCTCCTACCGAGGTGGCGGCACCTACACCAAGGGCGCCTTCCAGCAAGCCGCGAAAATTCTTC               TTCATGCTAGAGAACTCAACAAAAGTTGTATTTCTCATCACTGATGGATATTCCAAAATGGGGGAGACCCTAGACC               AATTGCAGCGTCACTGCGAGATTCAGGAGTGGAGATCTTCACTTTTGGCATATGGCAAGGGAACATTCGAGAGCTG               AATGACATGGCTTCCACCCCAAGGAGGAGCACTGTTACCTGCTACACAGTTTTGAAGAATTTGAGGCTTTTAGTCG               CCCTCTGTCATATGTTATTTGTAGATCTACCTTCTGGGAGTTTTATTCAAGATGATATGGTCCACTGCTAATATCT               TTGTGATGAAGGCAAGGACTGCTGTGACCGAATGGGAAGCTCAAATGTGGGGAAACACACAGGCCATTTTGAGTGC               ATCTGTGAAGGGGTATAACGGGAAAGGTAACTGCAGTATGACTGCACAGTTTGCCCATCGGTGGACATACAACCTG               AAGGCTCACCAGGAGGAATCAGCAGTTGCATTCCATGTCCTGATGAATCACACCTCTCCACCTGGAAGCACATC               CCCTGAAAGACTGTGTCTGCAGAGAGTACAGGGCATCTGGCCAGACCTGTGAAAAGTTGTCCACTGCCCTGCCCTG               AAGCCTCCCGAAAATGGTTACTTTATCCAAAACACTTGCAACAACCACTTCAATGCAGCCTGTGGGGTCCGATGTC               ACCCTGGATTTGATCTTGTGGGAAGCAGCATCATCTTATGTCTACCCAATGGTTTGTGGTCCGGTTCAGACAGCTA               CTGCAGAGTAAGAACATGTCCTCATCTCCGCCAGCCGAACATGGCCACATCAGCTGTTCTACAAGGGAATGTTA               TATAAGACAACATGTTTGGTTGCCTGTGATGAAGGGTACAGGCTAGAAGGCAGTGATAAGCTTACTTGTCAAGGAA               ACAGCCAGTGGGATGGGCCAGAACCCCGGTGTGTGGAGCGCCACTGTTCCACCTTTCAGATGCCCAAGATGTCAT               CATATCCCCCCACAACTGTGGCAAGCAGCCAGCCAATTTGCGACGGATCTGCTATGTAAGTTGCCGCAAGGGTTC               ATTTTATCTGGAGTCAAGAATGCTGAGATGTACCACTTCTGGAAAATGGAAATGTCGGAGTTCAGGCAGCTGTGT               GTAAAGACGTGGAGGCTCCTCAATCAACTGTCCTAAGGACATAGAGGCTAAGACTCTGGAACAGCAAGATTCTGC               CAATGTTACCTGGCAGATTCCAACAGCTAAAGACAACTCTGGTGAAAGGTGTCAGTCCACGTTCATCCAGCTTTC               ACCCCACCTTACCTTTTCCCAATTGGAGATGTTGCTATCGTATACACGGAACTGACCTATCCGGCAACCAGGCCA               GCTGCATTTTCCATATCAAGGTTATTGATGCAGAACCACCTGTAATAGACTGGTGCAGATCTCCACCTCCCGTCAA               GGTCTCGGAGAAGGTACATGCCGCAAGCTGGGATGAGCCTCAGTTCTCAGACAACTCAGGTGCTGAATTGGTCA               ACCAGAiAAGTCATACACAAGGAGACCTTTTCCCTCAAGGGGAGACTATAGTACAGTATACAGCCACTGACCCC               GCAATAACAGGACATGTGATATCCATATTGTCATGGTTCTCCCTGTGAAJAATTCCATTCACACCTGTAATGG               GGATTTTATATGCACTCCAGATAATACTGGAGTCAACTGTACATTAACTTGCTTGGAGGGCTATGATTTCACAGAA               GGGTCTACTGACAAGTATTATTGTGCTTATGAAGATGGCGTCTGGAAACCAACATATACCACTGAATGGCCAGACT               GTGCCAGTAAAGCGTTTTGCACCACGGGTTAAGTCCTTTGAGATGTTCTACAAAAAGCAGCTCGTTGTGATGACAC               AGATCTGATGAAGAAAGTTTTCTGAAGCATTTGAGACGACCCTGGGAAAATGGTCCCATCATTTTGTAGTGATGCA               GAGGACATTGACTGCAGACTGGAGGAGAACCTGACCAAAAAATATTGCCTAGAATATAATTATGACTATGAAAATG               GCTTTGCAATTGGTCCAGGTGGCTGGGGTGCAGCTAATAGGCTGGATTACTCTTACGATGACTTCCTGGACTGT               GCAAGAAACAGCCACAAGCATCGGCAATGCCAAGTCCTCACGGATTAAAAGAAGTGCCCCATTATCTGACTATAAA               ATTAAGTTAATTTTTTAACATCACAGCTAGTGTGCCATTACCCGATGAAAGAATGATACCCTTGAATGGGAAAATC               AGCAACGACTCCTTCAGACATTGGAAACTATCACAAATAAACTGAAAAGGACTCTCAACAAAGACCCCATGTATTC               CTTTCAGCTTGCATCAGAAATACTTATAGCCGACAGCAATTCATTAGAAACAAAAGGCTTCCCCCCCTTCTGCAGA               CCAGGCTCAGTGCTGAGAGGGCGTATGTGTGTCAATTGCCCTTTGGGAACCTATTATAATCTGGAACATTTCACCT               GTGAAAGCTGCCGGATCGGATCCTATCAAGATGAAGAAGGGCAACTTGAGTGCAAGCTTTGCCCCTCTGGGATGTA               CACGGAATATATCCATTCAAGAAACATCTCTGATTGTAGCTTCAGTGTAAAACAAGGCACCTACTCATACAGTGGA               CTTGAGACTTGTGAATCGTGTCCACTGGGCACTTATCAGCCAAAATTTGGTTCCCGGAGCTGCCTCTCGTGTCCAG               AAAACACCTCAACTGTGAAAAGAGGAGCCGTGAACATTTCTGCATGTGGAGTTCCTTGTCCAGAAGGAAAATTCTC               GCGTTCTGGGTTAATGCCCTGTCACCCATGTCCTCGTGACTATTACCAACCTAATGCAGGGAAGGCCTTCTGCCTG               GCCTGTCCCCTTTTATGGAACTACCCATTCGCTGGTTCCAGATCCATCACAGAATGTTCAAGTTTTAGTTCAACTT               TCTCAGCGGCAGAGGAAGTGTGGTGCCCCCTGCCTCTCTTGGACATATTAAAAJAAGAGGCATGAATCAGCAGTCA               GGCAAGTCATGAATGCTTCTTTAACCCTTGCCACAATAGTGGAACCTGCCAGCAACTTGGGCGTGGTTATGTTTGT               CTCTGTCCACTTGGATATACAGGTTTAAAGTGTGAAACAGACATCGATGAGTGCAGCCCACTGCCTTGCCTCAACA               ATGGAGTTTGTAGACCTAGTTGGGGAATTCATTTGTGAGTGCCCCATCAGGTTACACAGGTTAAGCACTGTGAATT               GAACATCAATGAATGTCAGTCTAATCCATGTAGAAATCAGGCCACCTGTGTGGATGAATTAAATTCATACAGTTGT               AAATGTCAGCCAGGATTTTCAGGCAAAGGTGTGAAAACAGGTATGTATCAACTCAGTGTTATTAATAACCTTAATA               ATGCAGTCTGTGAAGACCAGGTTGGGGGATTCTTGTGCAAATGCCCACCTGGATTTTTGGGTACCCGATGTGGAA               GAACGTCGATGAGTGTCTCAGTCAGCCATGCAAATGGAGCTACCTGTAAGACGGTGCCAATAGCTTCAGGTGC               CTGTGTGCAGCTGGCTTCACAGGATCACACTGTGAATTGAACATCAATGAATGTCAGTCTAATCCATGTAGAAATC               AGGCCACCTGTGTGGATGAATTAAATTCATACAGTTGTAAATGTCAGCCAGGATTTTCAGGCAAAAGGTGTGAAAC               AGAACAGTCTACAGGCTTTAACCTGGATTTTGAAGTTTCTGGCATCTATGGATATGTCATGCTAGATGGCATGCTC               CCATCTCTCCATGCTCTAACCTGTACCTTCTGGATGTCCTCTGACGACATGAACTATGGAAACACGGAAATCTCCT               ATGCAGTTGATAACGGCAGCGACAATACCTTGCTCCTGACTGATTATAACGGGGTGGGTTCTTTATGAAATGGCAG               GGAAGATAACAACTGTCCCTCGGTGAATGATGGCAGATGGCATCATATTGCAATCACTTGGACAAAAAGTACTGGT               GGAGCCTGGAGGGTCTATATATGGGGAAJAATTATCTGACGGTGGTACTGGCCTCTCCATTGGCAAGCCATACCTG               GTGGCGGTGCATTAGTTCTTGGGCAAGAGCAAGACAAAAGGAGAGGGGTTCAACCCGGCTGAGTCTTTTTGTGGGG               CTCCATAAGCCAGCTCAACCTCTGGGACTATGTCCTGTCTCCACAGCAGGTGAAGTCACTGGCTACCTCCTGCCCA               GAGGAACTCAGTAAAGGAAACGTGTTAGCATTGGCCTGATTTCTTGTCAGGAATTGTGGGAAAGTGAAGATCGATT               CTAAGAGCATATTTTGTTCTGATTGCCCACGCTTGGGAGGGTCAGTGCCTAATCTGAGAACTGCATCTGAAGATTT               AAAACCAGGTTCAAAGTCAAATCTGTTCTGTGAACCAGGCTTCCAGCTGGTCGGGAACCCTGTGCAGTACTGTCTG               AATCAAGGACAGTGGACACAACCACTCCCCCACTGTGAACGCATTCGCTGTGGGGTGCCACCTCCTTTGGAGAATG               GCTTCCATTCAGCCGATGACTTCTATGCTGGCAGCAAAGTAACCTACCAGTGCAACAATGGCTACTATCTATTGGG               TGACTCAAGGATGTTCTGTACAGATAATGGGAGCTGGAACGGCGTTTCACCATCCTGCTTAGATGTCGATGAGTGT               GCAGTTGGATCAGATTGTAGTGAGCATGCTTCTTGCCTGAACGTAGATGGATCCTACATATGTTCATGTGTCCAAC               CGTACACAGGATGGGAAAAAACTGTGCAGAACCTATAAAATGTAAAGGCTCCAGGAAATCCGGAAAATGGCCACTC               CTCAGGTGAGATTTATACAGTAGGTGCCGAAGTCACATTTTCGTGTCAGGAAGGATACCAGTTGATGGGAGTAACC               AAAATCACATGTTTGGAGTCTGGAGAATGGAAATCATCTAATACCATATTGTAAGCTGTTTCATGTGGTAAACCGG               CTATTCCAGAAAATGGTTGCATTGAGGAGTTAGCATTTACTTTTGGCAGCAAAGTGACATATAGGTGTAATAAAGG               ATATACTCTGGCCGGTGATAAAGAATCATCCTGTCTTGCTAACAGTTCTTGGAGTCATTCCCCTCCTGTGTGTGAA               CCAGTGAAGTGTTCTAGTCCGGAAATATAATAATGGAAATATATTTTGAGTGGGCTTACCTACCTTTCTACTGGGA               CATCATATTCATGCGATACAGGATACAGCTTACAGGGCCCTTCCATTATTGAATGCACGGCTTCTGGCATCTGGGA               CAGAGCGCCACCTGCCTGTCACCTCGTCTTCTGTGGAGAACCACCTGCCATCAAGATGCTGTCATTACGGGGAAAT               AACTTCACTTTCAGGAACACCGTCACTTACACTTGCAAAGAAGGCTATACTCTTGCTGGTCTTGACACCATTGAAT               GCCTGGCCGACGGCAAGTGGAGTAGAAGTGACCAGCAGTGCCTGGCTGTCTCCTGTGATGAGCCACCAATTGTGGA               CCACGCCTCTCCAGAGACTGCCCATCGGCTCTTTGGAGACATTGCATTCTACTACTGCTCTGATGGTTACAGCCTA               GCAGACAATTCCCAGCTTCTCTGCAATGCCCAGGGCAAGTGGGTACCCCCAGAAGGTCAAGACATGCCCCGTTGTA               TAGCTCATTTCTGTGAAAAACCTCCATCGGTTTCCTATAGCATCTTGGAATCTGTGAGCAAAGCAAAATTTGCAGC               TGGCTCAGTTGTGAGCTTTAAATGCATGGAAAGGCTTTGTACTGAACACCTCAGCAAGATTGAATGTATGAGAGGT               GGGCAGTGGAACCCTTCCCCCATCTCAATCCAGTGCATCCCTGTGCGGTGTGGAGAGCCACCAAGCATCATGAATG               GCTATGCAAGTGGATCAAACTACAGTTTTGGAGCCATGGTGGCTTACAGCTGCAAAAGGGGGTTCTACATCAAAGG               GGAAAAGAAGAGCACCTGCGAAGCCACAGGGCAGTGGAGTAGTCCTATACCGACGTGCCACCCGGTATCTTGTGGT               GAACCACCTAAGGTTGAGAATGGCTTTTCTGGAGCATAAACTGGCAGGATCTTTGAGAGTGAAGTGAGGTATCAGT               GTAACCCGGGCTATAAGTCAGTCGGAAGTCCTGTATTTGTCTGCCAAGCCAATCGCCACTGGCACAGTGAATCCCC               TCTGATGTGTGTTCCTCGACTGTGGAAAAACCTCCCCCCGATCCAGAATGGCTTCATGAAAGGAGAAAACTTTGAA               GTAGGGTCCAAGGTTCAGTTTTTCTGTAATGAGGGTTATGAGCTTGTTGGTGACAGTTCTTGGACATGTCAGAAAT               CTGGCAAATGGAATAAGAAGTCAAATCCAAAGTGCATGCCTGCCAAGTGCCCAGAGCCGCCCCTCTTGGAAAACCA               GCTAGTATTAAAGGAGTTGACCACCGAGGTAGGAGTTGTGACATTTTCCTGTAAAGAAGGGCATGTCCTGCAAGGC               CCCTCTGTCCTGAATAGCTTGCCATCCCAGCAATGGAATGACTCTTTCCCTGTTTGTAAGATTGTTCTTTGTACCC               CACCTCCCCTAATTTCCTTTGGTGTCCCCATTCCTTCTTCTGCTCTTCATTTTGGAAGTACTGTCAAGTATTCTTG               TGTAGGTGGGTTTTTCCTAAGAGGAAATTCTACCACCCTCTGCCAACCTGATGGCACCTGGAGCTCTCCACTGCCA               GAATGTGTTCCAGTAGAATGTCCCCAACCTGAGGAAATCCCCAATGGAATCATTGATGTGCAAGGCCTTGCCTATC               TCAGCACAGCTCTCTATACCTGCAAGCCAGGCTTTGAATTGGTGGGAAATACTACCACCCTTTGTGGAGAAAATGG               TCACTGGCTTGGAAGGAAAACCAACATGTAAAGCCATGAGTGCCTGAAACCCAAGGAGATTTTGAATGGCAAATTC               TCTTACACGGACCTACACTATGGACAGACCGTTACCTACTCTTGCAACCGAGGCTTTCGGCTCGAAGGTCCCAGTG               CCTTGACCTGTTTAGAGACAGGTGATTGGGATGTAGATGCCCCATCTTGCAATGCCATCCACTGTGATTCCCCACA               ACCCATTGAAAATGGTTTTGTAGAAGGTGCAGATTACAGCTATGGTGCCATAATCATCTACAGTTGCTTCCCTGGG               TTTCAGGTGGCTGGTCATGCCATGCAGACCTGTGAAGAGTCAGGATGGTCAAGTTCCATCCCAACATGTATGCCAA               TAGACTGTGGCCTCCCTCCTCATATAGATTTTTGGAGACTGTACTAACTCAAGATGACCAGGGGATATTTTGAGCA               AGAAGACGACATGATGGAAGTTCCATATGTGACTCCTCACCCTCCTTATCATTTGGGAGCAGTGGCTAAAACCTGG               GAAAAATACAAGGAGTCTCCTGCTACACATTCATCAACTTTCTGTATGGTACAATGGTTTCATACACCTGTAATC               CAGGATATGAACTTCTGGGGAACCCTGTGCTGATCTGCCAGGAAGATGGAACTTGGAATGGCAGTGCACCATCCTG               CATTTCAATTGAATGTGACTTGCCTACTGCTCCTGAAAATGGCTTTTTGCGTTTTACAGAGACTAGCATGGGAAGT               GCTGTGCAGTATAGCTGTAAACCTGGACACATTCTAGCAGGCTCTGACTTAAGGCTTTGTCTAGAGAATAGAAAGT               GGAGTGGTGCCTCCCCACGCTGTGAAGCCATTTCATGCAAAAAGCCAAATCCAGTCATGAATGGATCCATCAAAGG               AAGCAACTACACATACCTGAGCACGTTGTACTATGAGTGTGACCCCGGATATGTGCTGAATGGCACTGAGAGGAGA               ACATGCCAGGATGACAAAAACTGGGATGAGGATGAGCCCATTTGAATTCCTGTGGACTGCAGTTCACCCCCAGTCT               CAGCCAATGGCCAGGTGAGGAGGAGACGAGTACACATTCCAAAAGAGATTGAATACACTTGCAATGAAGGGTTCTT               GCTTGAGGGAGCCAGGAGTCGGGTTTGTCTTGCCAAAATGGAGTTGGAGTGAGCCACTCCCGACTGTGTGCCTGTC               AGATGTGCCACCCCGCCACAACTGGCCAATGGGGTGACGGAAGGCCTGGACTATGGCTTCATGAAGGAAGTAACAT               TCCACTGTCACGAGGGCTACATCTTGCACGGTGCTCCAAAACTCACCTGTCAGTCAGATGGCAACTGGGATGCAGA               GATTCCTCTCTGTAAACCAGTCACTGTGGACCTCCTGAAGATCTTGCCCATGGTTTCCCTAATGGTTTTTTCCTTT               ATTCATGGGGGCCATATACAGTATCAGTGCTTTCCTGGTTATAAGCTCCATGGATTCATCAAGGGAAGGTGCCTCT               CCAATGGCTCCTGGAGTGGCAGCTCACCTTCCTGCCTGCCTTGCAGATGTTCCACACCAGTAATTGAATATGGAAC               TGTCAATGGGGACAGATTTTGACTGTGGAAGGCAGCCCGGATTCAGTGCTTCAAGGCTTCAAGCTCCTAGGACTT               TCTGAAATCACCTGTGAAGCCGATGGCCAGTGGAGCTCTGGGTTCCCCCACTGTGAACACACTTCTTGTGGTTCTC               TTCCAATGATACCAAATGCGTTCATCAGTGAGACCAGCTCTTGGAAGGAAAATGTGATAACTTACAGCTGCAGGTC               TGGATATGTCATACAAGGCAGTTCAGATCTGATTTGTACAGAGAAGGGGTATGGAGCCAGCCTTATCCAGTCTGT               GAGCCCTTGTCCTGTGGGTCCCCACCGTCTGTCGCCAATGCAGTGGCAACTGGAGAGGCAAACACCTATGAAGTG               AAGTGAACTCAGATGTCTGGAAGGTTATACGATGGATACAGATACAGATACATTCACCTGTCAGAAAAGATGGTCG               CTGGTTCCCTGAGAGAATCTCCTGCAGTCCTAAAAAATGTCCTCTCCCGGAAAACATAACACATATACTTGTACAT               GGGGACGATTTCAGTGTGAATAGGCAAGTTTCTGTGTCATGTGCAGAAGGGTATACCTTTGAGGGAGTTAACATAT               CAGTATGTCAGCTTGATGGAACCTGGGAGCCACCATTCTCCGATGAATCTTGCAGTCCAGTTTCTTGTGGGAAACC               TGAAAGTCCAGAACATGGATTTGTGGTTGGCAGTTAAATACACCTTTGAAGCACAATTATTTATCAGTGTGAGCCT               GGCTATGACTAGAGGGGGAACAGGGAACGTGTCTGCCAGGAGAACAGACAGTGGAGTGGAGGGGTGGCAATATGCA               AAGAGACCAGGTGTGAAACTCCACTTGAATTTCTCAATGGGAAAGCTGACATTGAAAACAGGACGACTGGACCCAA               CGTGGTATATTCCTGCCAAGAGGCTACAGTCTTGAAGGGCCATCTGAAGGAACACTGCACAGAAAATGGAACCTGG               AGCCACCCAGTCCCTCTCTGCAACCAAATCCATGCCCTGTTCCTTTTGTGATTCCCGAGAATGCTCTGCTGTCTG               AAAAGGAGTTTTATGTTGATCAGAATGTGTCCATCAAATGTAGGGAAGGTTTTCTGCTGCAGGGCCACGGCATCAT               TACCTGCAACCCCGACGAGACGTGGACACAGACAAGCGCCAAATGTGAAAAAATCTCATGTGGTCCACCAGCTCAC               GTAGAAAAATGCAATTGCTCGAGGCGTACATTATCAATATGGAGACATGATCACTACTCATGTTACAGTGGATACA               TGTTGGAGGGTTTCCTGAGGAGTGTTTGTTTAGAAAATGGAACATGGACATCACCTCCTATTTGCAGAGCTGTCTG               TCGATTTCCATGTCAGAATGGGGGCATCTGCCAACGCCCAAATGCTTGTTCCTGTCCAGAAAGCTGGATGGGGCGC               CTCTGTGAAGAACCAATCTGCATTCTTCCCTGTCTGAACGGAGGTCGCTGTGTGGCCCCTTACCAGTGTGACTGCC               CGCCTGGCTGGACGGGGTCTCGCTGTCATACAGCTGTTTTGCCAGTCTCCCTGCTTAATGGTGGAAAATGTGTAAG               ACCAAACCGATGTCACTGTCTTTCTTCTTGGACGGGACATAACTGTTCCAGGAAAAGGAGGACTGGGTTT TAA   CCA                   CTGCACGACCATCTGGCTCTCCCAAAAGCAGGATCATCTCTCCTCGGTAGTGCCTGGGCATCCTGGAACTTATGCA                   AAGAAAGTCCAACATGGTGCTGGGTCTTGTTTAGTAAACTTGTTACTTGGGGTTACTTTTTTTATTTTGTGATATA                   TTTTGTTATTCCTTGTGACATACTTTCTTACATGTTTCCATTTTTATATGCCTGTATTTTCTATATAAAAAAATTA                   TATTAAATAGATGCTGCTCTACCCTCACACAAAATGTACATATTCTGCTGTCTATTGGGAAAGTTCCTGGTACACATT                   TTTATTCAGTTACTTAAAATGATTTTTCCATTAAAGTATATTTTGCTACTAAATAAAAAAAAAA                    
 
       [0096] The sequence of NOV2a was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof  
       [0097] The DNA sequence and protein sequence for a novel polydom-like gene were obtained by SeqCallingTM Technology and are reported here as NOV2a. These methods used to amplify NOV2a cDNA are described in Example 2.  
       [0098] The NOV2a polypeptide (SEQ ID NO: 6) encoded by SEQ ID NO: 5 is 3570 amino acid residues in length and is presented using the one-letter amino acid code in Table 2B. The SignalP, Psort and/or Hydropathy results predict that NOV2a has a signal peptide and is likely to be localized extracellularly with a certainty of 0.3846. In alternative embodiments, a NOV2a polypeptide is located to the lysosome (lumen) with a certainty of 0.1900, the endoplasmic reticulum (membrane) with a certainty of 0.1000, or the endoplasmic reticulum (lumen) with a certainty of 0.1000. The SignalP predicts a likely cleavage site for a NOV2a peptide between amino acid positions 16 and 17, i.e. at the dash in the sequence VSG-WA.  
               TABLE 2B                       Encoded NOV2a Protein Sequence                                        (SEQ ID NO:6)                         MRRTCAACWGLALVSGWATFQQMSPSRNFSFRLFPETAPGAAGSIPAPPAPGDEAAGSRVERLGQAFRVRLLR                   ELSERLELVFLVDDSSSVGEVNFRSELMFVRKLLSDFPVVPTATRVAIVTFSSKNYVVPRVDYISTRRRARQHK               CALLLQEIPAISYRGGGTYTKGAFQQAAQILLHENSTKXJAAJFLITDGYSNGGDPRPIAASLRDSGVEIFTFG               IWQGNIRELNDMASTPKEEHCYLLHSFEEFEALVALCHMLFVDLPSGSFIQDDMVHCSYLCDEGKDCCDRMGS               CKCGKHTGHFECICEKGYNGKGLQYDCTVCPSGTYKPEGSPGGISSCIPCPDENHTSPPGSTSPEDCVCREGY               RASGQTCEVVHCPALKPPENGYFIQNTCNNHFNAACGVRCHPGAALVGSSIILCLPNGLWSGSESYCRVRTCP               HLRQPKHGHISCSTREMLYKTTCLVACDEGYRLEGSDKLTCQGNSQAAGPEPRCVERHCSTFQMPKDVIISPH               NCGKQPAKFGTICYVSCRQGFILSGVKEMLRCTTSGKVGVQAAVCKDVEAPQINCPKDIEAKTLEQQDSAN               VTWQIPTAKDNSGEKVSVHVHPAFTPPYLFPIGDVAIVYTATDLSGNQASCIFHIKVIDAAPPVIDWCRSPPP               VQVSEKVHAASWDEPQFSDNSGAELVITRSHTQGDLFPQGETIVQYTATDPSGAARTCDIHIVIKGSPCEIPF               TPVNGDFICTPDNTGVNCTLTCLEGYDFTEGSTDKYYCAYEDGAAKPTYTTEWFDCASKRFANHGFKSFEMFY               KAARCDDTDLMKKFSEAFETTLGKMVPSFCSDAEDIDCRLEENLTKKYCLENYDYENGFAIGPGGWGAANRL               DYSYDDFLDTVQETATSIGNAKSSRIKRSAPLSDYKIKLIFNITASVPLPDERNDTLEWENQQRLLQTLETIT               NKLKRTLNKDPMYSFQLASEILIADSNSLETKKASPFCRPGSVLRGRMCVNCPLGTYYNLEHFTCESCRIGSY               QDEEGQLECKLCPSGMYTEYIHSRNISDCKAQCKQGTYSYSGLETCESCPLGTYQPKFGSRSCLSCPENTSTV               KRGAVNISACGVPCPEGKFSRSGLMPCHPCPRDYYQPNAGKAFCLACPFYGTTPFAGSRSITECSSFSSTFSA               AEESVVPPASLGHIKKRHEISSQASHECFFNPCAASGTCQQLGRGYVCLCPLGYTGLKCETDIDECSPLPCLN               NGVCKDLVGEFICECPSGYTGKHCELNINECQSNPCRNQATCVDELNSYSCKCQPGFSGKRCETGMYQLSVIN               NLNNAVCEDQVGGFLCKCPPGFLGTRCGKVDECLSQPCYAAGATCAAGAASFRCLCAAGFTGSHCELNINECQ               SNPCRNQATCAAELNSYSCKCQPGFSGAACETEQSTGAALDFEVSGIYGLDGMLPSLHALTCTFWMKSSD               DMNYGTPISYAVDNGSDNTLLLTDYNGWVLYVNGREKITNCPSVNDGRWHHIAITWTSTGGAWRVYINGELSD               GGTGLSIGKAIPGGGALVLGQEQDKKGEGFNPAESFVGSISQLAALWVLSPQQVKSAATSCPEELSKGNVLA               WPDFLSGIVGKVKIDSKSIFCSDCPRLGGSVPHLRTASEDLKPGSKVNLFCEPGFQLVGNPVQYCLNQGQWTQ               PLPHCERIRCGVPPPLENGFHSADDFYAGSTVTYQCNNGYYLLGDSRMFCTDNGSWNGVSPSCLDVDECAVGS               DCSEHASCLNVDGSYICSCVPPYTGDGKNCAEPIKCKAPGNPENGHSSGEIYTVGAEVTFSCQEGYQLMGVTK               ITCLESGEWHLIPYCKAVSCGKPAIPENGCIEELAFTFGSAATYRCNKGYTAAGDKESSCLAANSSWSHSPPV               CEPVKCSSPENTNNGKYILSGLTYLSTASYSCDTGYSLQGPSIIECTASGIWDRAPPACHLVFCGEPPAIKDA               VITGNNFTFRNTVTYTCKEGYTLAGLDTIECLADGKWSRSDOOCLAVSCDEPPIVDHASPETAHRLFGDIAFY               YCSDGYSLADNSQLLCNAQGKWVPPEGQDMPRCIAHFCEKPPSVSYSILESVSKAKFAAGSVVSFKCMEGFVL               NTSAKIECMRGGQWNPSPMSIQCIPVRCGEPPSIMNGYASGSNYSFGAMVAYSCNKGFYIKGEKKSTCEATGQ               WSSPIPTCHPVSCGEPPKVENGFLEHTTGRIFESEVRYQCNPGYKSVGSPVFVCQANRHWHSESPLMCVPLDC               GKPPPIQNGFMKGEAAFEVGSKVQFFCNEGYELVGDSSWTCQKSGKAAKSNPKCMPAACPEPPLLENQLVLKE               LTTEVGVVTFSCKEGHVLQGPSVLKCLPSQQWNDSFPVCKIVLCTPPPLISFGVPIPSSALHFGSTVKYSCVG               GFFLRGNSTTLCQPDGTWSSPLPECVPVECPQPEEIPNGIIDVQGLAYLSTALYTCKPGFELVGNTTTLCGEN               GHWLGGKPTCKAIECLKPKEILNGKFSYTDLHYGQTVTYSCNRGFRLEGPSALTCLETGDWDVDAPSCNAIHC               DSPQPIENGFVEGAAAYSYGAIIIYSCFPGFQVAGAAQTCEESGWSSSIPTCMPIDCGLPPHIDFGDCTKLKD               DQGYFEQEDDMMEVPYVTPHPPYHLGAVAKTWENTKESPATHSSNFLYGTMVSYTCNPGYELLGNPVLICQED               GTWNGSAPSCISIECDLPTAPENGFLRFTETSMGSAVQYSCKPGHIAAGSDLRLCLEAAAASGASPRCEAISC               KKPNPVMNGSIKGSNYTYLSTLYYECDPGYVLNGTERRTCQDDYAAEDEPICIPAACSSPPVSANGQVRGDE               YTFQKEIEYTCNEGFLLEGAASRVCLAAGSWSGATPDCVPAACATPPQLAAGVTEGLDYGFMKEVTFHCHEGY               ILHGAPKLTCQSDGNWDAEIPLCKPVNCGPPEDLAHGFPNGFSFIHGGHIQYQCFPGYKLHGNSSRRCLSNGS               WSGSSPSCLPCRCSTPVIEYGTVNGTDFDCGYIQCFKGFKLLGLSEITCEADGQWSSGFPHCEHTSCGSL               PMIPNAFISETSSWKENVITYSCRSGYVIQGSSDLICTEKGVWSQPPVCEPLSCGSPPSVANAVATGEAHTY               ESEVKLRCLEGYTMDTDTDTFTCQKDGRWFPERISCSPKKCPLPENITHILVHGDDFSVNRQVSVSCAEGYTF               EGVNISVCQLDGTWEPPFSDESCSPVSCGKPESPEHGFVVGSKYTFESTIIYQCEPGYELEGNRERVCQENRQ               WSGGVAICKETRCETPLEFLNGKADIENRTTGPNVVYSCNRGYSLEGPSEAHCTENGTWSHPVPLCKPNPCPV               PFVIPENALLSEKEFYVDQNVSIKCREGFLLQGHGIITCNPDETWTQTSAKCEKISCGPPAHVENAIARGVHY               QYGMITYSCYSGYMLEGFLRSVCLENGTWTSPPICRAVCRFPCQNGGICQRPNACSCPEGWMGRLCEEPICI               LPCLGGRCVAPYQCDCPPGWTGSRCHTAVCQSPCLNGGKCAAPAACHCLSSWTGAACSRAARTGF                  
 
       [0099] NOV2b  
       [0100] In an alternative embodiment, a NOV2 variant is NOV2b (alternatively referred to herein as CG50646-05), which includes the 11152 nucleotide sequence (SEQ ID NO: 7) shown in Table 2C. An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 77-79 and ending with a termination codon at nucleotides 10781-10783. The start and stop codons of the open reading frame are highlighted in bold type. Putative untranslated regions are underlined and found upstream from the initiation codon and downstream from the termination codon.  
               TABLE 2C                       NOV2b Nucleotide Sequence                                        (SEQ ID NO:7)                           CAATTGGTCTAGGGTCTCCCCCCATTGGAATATCCATCAGTGATGAGAAATACAACGTTTGTTGAGTTTTC                       TCTAGC   ATG AGAAGAAATTTGCGCGGCTTGCTGGGGTCTGGCGCTCGTTTCGGGCTGGGCGACCTTTCAGC               AGATGTCCCCGTCGCGAAATTTCAGCTTCCGCCTCTTCCCCGAGACCGCGCCCGGGGCCCCCGGGAGTAT               CCCCGCGCCGCCCGCTCCTGGCGACGAAGCGGCGGGGAGCAGAGTGGAGCGGCTGGGCAAGGCGTTCCGC               GTGCGGCTGCTGCGGGAGCTCAGCGAGCGCCTGGAGCTTGTCTTCCTGGTGGATGATTCGTCCAGCGTGG               GCGAAGTCAACTTCCGCAGCGAGCTCATGTTCGTCCGCAAGCTGCTGTCCGACTTCCCCGTGGTGCCCAC               GGCCACGCGCGTGGCCATCGTGACCTTCTCGTCCAAGAACTACGTGGTGCCGCGCGTCGATTACATCTCC               ACCCGCCGCGCGCGCCAGCACAAGTGCGCGCTGCTCCTCCAAGAGATCCCTGCCATCTCCTACCGAGGTG               GCGGCACCTACACCAAGGGCGCCTTCCAGCAAGCCGCGCAAATTCTTCTTCATGCTAGAGAAAACTCAAC               AAAAGTTGTATTTCTCATCACTGATGGATATTCCAATGGGGGAGACCCTAGACCAATTGCAGCGTCACTG               CGAGATTCAGGAGTGGAGATCTTCACTTTTGGCATATGGCAAGGGAACATTCGAGAGCTGAATGACATGG               CTTCCACCCCAAGGAGGAGCACTGTTACCTGCTACACAGTTTTTGAAGAATTTGAGGCTTTAGCTCGCCG               GGCATTGCATGAAGATCTACCTTCTGGGAGTTTTATTCAAGATGATATGGTCCACTGCTCATATCTTTGT               GATGAGGGCAAGGACTGCTGTGACCGAATGGGAAGCTGAAAATGTGGGACACACACAGGCCATTTTGAGT               GCATCTGTGAAAGGGGTATTACGGGAAGGTCTGCAGTATGAAAATGCACAGCTTGCCCATCGGGGACATA               CAACCTGAAGCCTCACCAGGAGGAATCAGCAGTTGCATTCCATGTCCCGATGAAAATCACAACCTCTCCA               CCTCGAAGCACATCCCCTGAAGACTGTGTCTGCAGAGAGGGATACAGGGCATCTGGCCAGACCTGTGAAC               TTGTCCACTGCCCTGCCCTGAAGCCTCCCGAAAATGGTTACTTTATCCAAAACACTTGCAACAACCACTT               CAATGCAGCCTGTGGGGTCCGATGTCACCCTGGATTTGATCTTGTGGGAAGCAGCATCATCTTATGTCTA               CCCAATGGTTTGTGGTCCGGTTCAGAGAGCTACTGCAGAGTAAGAACATGTCCTCATCTCCGCCAGCCGA               AACATGGCCACATCAGCTGTTCTACAAGGGAAATGTTATATAAGACAACATGTTTGGTTGCCTGTGATGA               AGGGTACAGACTAGAAGGCAGTGATAAGCTTACTTGTCAAGGAAACAGCCAGTGGGATGGGCCAGAACCC               CGGTGTGTGGAGCGCCACTGTTCCACCTTTCAGATGCCCAAGATGTCATCATATCCCCCCCACAACTGTG               GCAAGCAGCCAGCCAAATTTGGGACGATCTGCTATGTAAGTTGCCGCCAAGGGTTCATTTTATCTGGAGT               CAAAGAAATGCTGAGATGTACCACTTCTGGAAAATGGAATGTCGGAGTTCAGGCAGCTGTGTGTAAAGAC               GTGGAGGCTCCTCAAATCAACTGTCCTAAGGACATAGAGGCTAAGACTCTGGAACAGCAAGATTCTGCCA               ATGTTACCTGGCAGATTCCAACAGCTAAGACAACTCTGGTGAAAAAGGTGTAAGTCCGCQTTCATCCAGC               TTTCACCCCACCTTACCTTTTCCCAAATTGGAATGTTCGTATCGTATACACGGCAACTGACCTATCCGGC               AACCAGGCCAGCTGCATTTTCCATATCAAGGTTATTGATGCAGAACCACCTGTCATAGACTGGTGAAGAT               CTCCACCTCCCGTCCAGGTCTCGGAGAAGGTACATGCCGCAAGCTGGGATGAGCCTCAGTTCTCAGACAA               CTCAGGGGCTGAATTGGTCATTACCAGAAGTCATACACAAGGAGACCTTTTCCCTCAAGGGGAGACTATA               GTACAGTATACAGCCACTGACCCCTCAGGTAATAACAAGGATATGTGATATCCATATTGTCATGAAGGTT               CTCCCTGGGTGAATTCCATTCACACCTGTAATGGGGATTTTATATGCACTCCAGATAATACTGGAGTCAA               CTGTACATTAACTTGCTTGGAGGGCTACGATTTCACAGAAGGGTCTACTACAAAGTATTATTGTGCTTAT               GAAGATGGCGTCTGGAAACCAACATATACCACTGAATGGCCAGACTGTTGCCAAAAACGTTTTGCAAACC               ACGGGTTCAAGTCCTTTGAGATGTTCTACAAAGCAGCTCGTTGTGATGACTCAGATCTGATGAAGAAGTT               TTCTGAAGCATTTGAGACGACCCTGGGAAAAATGGTCCCATCATTTTGTAGTGATGCAGAGGACATTGAC               TGCAGACTGGAGGAGAACCTGACCAAAAATATTGCCTAGAATATAATTATGACTATGAAAAATGGCTTTG               CAATTGGTCCAGGTGGCTGGGGTGCAGCTAATAGGCTGGATTACTCTTACGATGACTTCCTGGACACTGT               GCAAGAAACAGCCACAAGCATCGGCAATGCCAAGTCCTCACGGATTAAAAGAAGTGCCCCATTATCTGAC               TATAATTAAGTTAATTTTTAACATCACAGCTAGTGTGCCATTACCCGATGAAAAAGAAATGATACCCTTG               AATGGGAAAATCAGCAACGACTCCTTCAGACATTGGAAACTATCACAAATAAACTGAAAAGGACTCTCAA               CAAAGACCCCCATGTATTCCTTTCAGCTTGCATCAGAAATACTTATAGCCGACAGCATTCAATTAGAACA               AAAAAGGCTTCCCCCTTCTGCAGACCAGGCTCAGTGCTGAGAGGGCGTATGTGTGTCAATTGCCCTTTGG               GAACCTATTATAATCTGGAACATTTCACCTGTGAAAGCTGCCGGATCGGATCCTATCAAGATGAAGAAGG               GCAACTTGAGTGCAAGCTTTGCCCCTCTGGGATGTACACGAATATATCCATTCAAAACAACATCTCTGAT               TGTAAAGCTCAGTGTAAACAAGGCACCTACTCATACAGTGGACTTGAGACTTGTGAATCGTGTCCACTGG               GCACTTATCAGCCAAAATTTGGTTCCCGGAGCTGCCTCTCGTGTCCAGAAAACACCTCAACTGTGAAAAG               AGGAGCCGTGAACATTTCTGCATGTGGAGTTCCTTGTCCAGAAGGAAAATTCTCGCGTTCTGGGTTAATG               CCCTGTCACCCATGTCCTCGTGACTATTACCAACCTAATGCAGGGAAGGCCTTCTGCCTGGCCTGTCCCT               TTTATGGAACTACCCCATTCGCTGGTTCCAGATCCATCACAGAATGTTCAAGTTTTAGTTCAACTTTCTC               AGCGGCAGAGGAAAGTGTGGTGCCCCCTGCCTCTCTTGGACATATTAAAAAGAGGCATGAAATCAGCAGT               CAGGCAGTCATGAATGCTTCTTTAACCCTTGCCACAATAGTGGAACCTGCCAGCTAACTTGGGCGTGGTT               ATGTTTGTCTCTGTCCACTTGGATATACAGGTTTAAAGTGTGAAACAGACATCGATGAGTGCAGCCCACT               GCCTTGCCTCAACATGGAGTTTGTAAAGACCTAGTTGGGGGAATTCATTTGTGAGTGCCAATCAGGTTAC               ACAGGTAAGCACTGTGAATTGAACATCAATGAATGTCAGTCTAATCCATGTAGAAATCAGGCCACCTGTG               TGGATGAATTAAATTCATACAGTTGTAATGTCAGCCAGGATTTTCAAGGCAAAAGGTGTGAAACAGGTAT               GTATCAACTCAGTGTTATTAATAACCTTAATAATGCAGTCTGTGAAGACCAGGTTGGGGGATTCTTGTGC               AAATGCCCACCTGGATTTTTGGGGTACCCGATGTGGAAGAACGTCGATGAGTGTCTCAGTCAGCCATGCA               AAAATGGAGCTACCTGTAATGACGGTGCCAATAGCTTCAGGTGCCTGTGTGCAGCTGGCTTCACAGGATC               ACACTGTGAATTGAACATCAATGAATGTCAGTCTAATCCATGTAGAAATCAGGCCACCTGTGTGGATGAA               TTAAATTCATACAGTTGTAAATGTCAGCCAGGATTTTCAGGCAAAAGGTGTGAAACAGAACAGTCTACAG               GCTTTAACCTGGATTTTGAAGTTTCTGGCATCTATGGATATGTCATGCTAGATGGCATGCTCCCATCTCT               CCATGCTCTAACCTGTACCTTCTGGATGAAATCCTCTGACGACATGAACTATGGAACACCAATCTCCTAT               GCAGTTGATAACGGCAGCGACAATACCTTGCTCCTGACTGATTATAACGGGTGGGTTCTTTATGTGAATG               GCAGGGAAAAGATAACAAACTGTCCCTCGGTGAATGATGGCAGATGGCATCATATTGCAATAACTTGGAC               AAGTACTGGTGGGAGCCTGGAGGGTCTATATAATGGGGAATTATCTGACGGTGGTACTGGCCTCTCCATT               GGCAAAGCCATACCTGGTGGCGGTGCATTAGTTCTTGGGCAAGAGCAAGACAAAAAAGGAGAGGGGTTCA               ACCCGGCTGAGTCTTTTGTGGGCTCCATAAGCCAGCTCAACCTCTGGGACTATGTCCTGTCTCAACAGAA               GGTGAAGTCACTGGCTACCTCCTGCCCAGAGGAACTCAGTAAAGGAAACGTGTTAGCATGGCCTGATTTC               TTGTCAGGAATTGTGGGGGAAGTGAAGATCGATTCTAAGAGCATATTTTGTTCTGATTGCCCACGCTTGG               GAGGGTCAGTGCCTCATCTGAGAACTGCATCTGAAGATTTAAAACCAGGTTCCAAAGTCAATCTGTTCTG               TGAACCAGGCTTCCAGCTGGTCGGGAACCCTGTGCAGTACTGTCTGAATCAAGGACAGTGGACACAACCA               CTCCCCCACTGTGAACGCATTCGCTGTGGGGTGCCACCTCCTTTGGAGAATGGCTTCCATTCAGCCGATG               ACTTCTATGCTGGCAGCACAGTAACCTACCAGTGCAACAATGGCTACTATCTATTGGGTGACTCAAGGAT               GTTCTGTACAGATAATGGGAGCTGGAACGGCGTTTAACCATCCTGCTTAGATGTCGATGAGTGTGCAGTT               GGATCAGATTGTAGTGAGCATGCTTCTTGCCTGAACGTAGATGGATCCTACATATGTTCATGTGTCCCAC               CGTACACAGGAGATGGGAAAAACTGTGCAGAACCTATAAAATGTAAGGCTCCAGGAAATCCGGAAAATGG               CCACTCCTCAGGTGAGATTTATACAGTAGGTGCCGAAGTAACATTTTCGTGTCAGGAAGGATACCAGTTG               ATGGGAGTAACCAAAATCACATGTTTGGAGTCTGGAGAATGGAATCATCTAATACCATATTGTAAAGCTG               TTTCATGTGGTAAACCGGCTATTCCAGAAAATGGTTGCATTGAGGAGTTAGCATTTACTTTTGGCAGCAA               AGTGACATATAGGTGTAATAAAAGGATATACTCTGGCCGGTGATAAGAATCATCCTGTCTTGCTAACAGT               TCTTGGAGTCATTCCCCTCCTGTGTGTGAACCAGTGAAGTGTTCTAGTCCGGAAAAATATAATAATGGAA               AATATATTTTGAGTGGGCTTACCTACCTTTCTACTGCATCATATTCATGCGATACAGGATACAGCTTACA               GGGCCCTTCCATTATTGAATGCACGGCTTCTGGCATCTGGGACAGAGCGCCACCTGCCTGTCACCTCGTC               TTCTGTGGAGAACCACCTGCCATCAAAGATGCTGTCATTACGGGGAATAACTTCACTTTCAGGAACACCG               TCACTTACACTTGCAAGAAGGCTATACTCTTGCTGGTCTTGACACCATTGAATGCCTGGCCGACGGCAAA               GTGGAGTAGAAGTGACCAQCAGTGCCTGGCTGTCTCCTGTGATGAGCCACCCATTGTGGACCACGCCTCT               CCAGAGACTGCCCATCGGCTCTTTGGAGACATTGCATTCTACTACTGCTCTGATGGTTACAGCCTAGCAG               ACAATTCCCAGCTTCTCTGCAATGCCCAGGGCAAGTGGGTACCCCCAGAAGGTCAAGACATGCCCCGTTG               TATAGCTCATTTCTGTGAAAAACCTCCATCGGTTTCCTATAGCATCTTGGAATCTGTGAGCAAAGCAAAA               TTTGCAGCTGGCTCAGTTGTGAGCTTTAAATGCATGGAAGGCTTTGTACTGAACACCTCAGCAAAGATTG               AATGTATGAGAGGTGGGCAGTGGAACCCTTCCCCCATGTCCATCCAGTGCATCCCTGTGCGGTGTGGAGA               GCCACCAAAGCATCATGAATGGCTATGCAAGTGGATCAACTACAGTTTTGGAGCCATGGTGGCTTACAGC               TGCAACAAGGGGTTCTACATCAAAGGGGAAAAGAAGAGCACCTGCGAAGCCACAGGGCAGTGGAGTAGTC               CTATACCGACGTGCCACCCGGTATCTTGTGGTGAACCACCTAAGGTTGAGAATGGCTTTCTGGAGCATAC               AACTGGCAGGATCTTTGAGAGTGAAGTGAGGTATCAGTGTAACCCGGGCTATAAGTCAGTCGGAAGTCCT               GTATTTGTCTGCCAAGCCAATCGCCACTGGCACAGTGAATCCCCTCTGATGTGTGTTCCTCTCGACTGTG               GAAAACCTCCCCCCCGATCCAGAATGGCTTCATGAGGAAAGAACTTTGAAGTAGGGTCCAAGGTTCAGTT               TTTCTGTAATGAGGGTTATGAGCTTGTTGGTGACAGTTCTTGGACATGTAAGAAATCTGGCAAATGGAAT               AAGAAGTCAAATCCAAAGTGCATGCCTGCCAAGTGCCCAGAGCCGCCCCTCTTGGAAAACCAGCTAGTAT               TAAAGGAGTTGACCACCGAGGTAGGAGTTGTGACATTTTCCTGTAAGGAAGGGAATGTCCTGCAAGGCCC               CTCTGTCCTGAATGCTTGCCATCCCAGCAATGGAATGACTCTTTCCCTGTTTGTAAGAATTGTTCTTTGT               ACCCCACCTCCCCTAATTTCCTTTGGTGTCCCCATTCCTTCTTCTGCTCTTAATTTTGGAAGTACTGTCA               AGTATTCTTGTGTAGGTGGGTTTTCCTAAGAGGAAATTCTACCACCCTCTGCCAAACCTGATGGCACCTG               GAGCTCTCCACTGCCAGAATGTGTTCCAGTAGAATGTCCCCAACCTGAGGAAATCCCCAATGGAATCATT               GATGTGCAAGGCCTTGCCTATCTCAGCACAGCTCTCTATACCTGCAAGCAAGGCTTTGAATTGGTGGGAA               ATACTACCACCCTTTGTGGAAAAGATGGTCACTGGCTTGGAGGAAAACCAACATGTAAAGCCATTGAGTG               CCTGAAACCCAAGGAGATTTGAAATGGCAAATTCTCTTACACGGACCTACACTATGGACAGACCGTTACC               TACTCTTGCAACCGAGGCTTTCGGCTCGAAGGTCCCAGTGCCTTGACCTGTTTACAGACAGGTGATTGGG               ATGTAGATGCCCCATCTTGCAATGCCATCCACTGTGATTCCCCACAACCCATTGAAAATGGTTTTGTAGA               AGGTGCAGATTACAGCTATGGTGCCATAATCATCTACAGTTGCTTCCCTGAATTTCAGGTGGCTGGTCAT               GCCATGCAGACCTGTGAAGAGTCAGGATGGTCAAGTTCCATCCCAAAATGTATGCCAATAGACTGTGGCC               TCCCTCCTCATATAGATTTTGGAGACTGTACTACTCAAGATGACCAGGGATATTTTGAGCAAGAAGACAG               CGACATGATGGAAGTTCCATATGTGACTCCTCACCCTCCTTATCATTTGGGAGCAGTGGCTAAAACCTGG               GAAAATACAAAGGAGTCTCCTGCTACACATTCATCAAACTTTCTGTATGGTACCATGGTTTCATACACCT               GTAATCCAGGATATGAACTTCTGGGGAACCCTGTGCTGATCTGCCAGGAAGATGGAACTTGGAATGGCAG               TGCACCATCCTGCATTTCAATTGAATGTGACTTGCCTACTGCTCCTGAAAATGGCTTTTTGCGTTTTACA               GAGACTAGCATGGGAAGTGCTGTGCAGTATAGCTGTAAACCTGGACACATTCTAGCAGGCTCTGACTTAA               GGCTTTGTCTAGAGAATAGAAGTGGAGTGGTGCCTCCCCACGCTGTGAAGCCATTTCATGCAAAAAAGCC               AAATCCAGTCATGAATGGATCCATCAAAGGAAGCAACTACACATACCTGAGCACGTTGTACTATGAGTGT               GACCCCGGATATGTGCTGAATGGCACTGAGAGGAGAACATGCAAGGATGACAAAACTGGGGATGAGGATG               AGCCCATTTGCATTCCTGTGGACTGCAGTTCACCCCCATCTCAGCCAAATGGCCAGGTGAGAGGAGACGA               GTACACATTCCAAAGAGATTGAATACACTTGCAATGAAGGGTTTCTTGGCTTGAGGGAGCCAGGAGTCGG               GTTTGTCTTGCCAATGGAAGTTGGAGTGGAGCCACTCCCGACTGTGTGCCTGTCAGATGTGCCACCCCGC               CACAACTGGCCAATGGGGTGACGGAAGGCCTGGACTATGGCTTCATGAAGGAAGTAACATTCCACTGTCA               CGAGGGCTACATCTTGCACGGTGCTCCAAAACTCACCTGTCAGTCAGATGGAACTGGGATGCAGAGATT               CCTCTCTGTAAACCAGTCAACTGTGGACCTCCTGAAGATCTTGCCCATGGTTTCCCTAATGGTTTTTCCT               TTATTCATGGGGGCCATATACAGTATCAGTGCTTTCCTGGTTATAAGCTCCATGGTTCATCAAGAAGAAG               GTGCCTCTCCAATGGCTCCTGGAGTGGCAGCTAACCTTCCTGCCTGCCTTGCAGATGTTCCACACCAGTA               ATTGAATATGGAACTGTCAATGGGACAGATTTTGACTGTGGAAGGCAGCCCGGATTCAGTGCTTCAAG               GCTTCAAGCTCCTAGGACTTTCTGAAATCACCTGTGAAGCCGATGGCCAGTGGAGCTCTGGGTTCCCCCA               CTGTGAACACACTTCTTGTGGTTCTCTTCCAATGATACCAAATGCGTTCATCAGTGAGACCAGCTCTTGG               AAGGAAAATGTGATAACTTACAGCTGCAGGTCTGGATATGTCATACAAGGCAGTTCAGATCTGATTTGTA               CAGAGAAAGGGGTATGGAGCCAGCCTTATCCAGTCTGTGAGCCCTTGTCCTGTGGGTCCCCACCGTCTGT               CGCCAATGCAGTGGCAACTGGAGAGGCACACACCTATGAAAGTGAAGTGAAACTCAGATGTCTGGAAGGT               TATACGATGGATACAGATACAGATACATTCACCTGTCAGAAGATGGTCGCTGGTTCCCTGAAGAGAATCT               CCTGCAGTCCTAAAAAATGTCCTCTCCCGGAAAAACATAACACATATACTTGTACATGGGACGATTTCAG               TGTGAATAGGCAAGTTTCTGTGTCATGTGCAGAAGGGTATACCTTTGAGGGAGTTAACATATCAGTATGT               CAGCTTGATGGAACCTGGGAGCCACCATTCTCCGATGAATCTTGCAGTCCAGTTTCTTGTGGGAAACCTG               AAAGTCCAGAACATGGATTTGTGGTTGGCAGTAAATACACCTTTGAAAGCACAATTATTTATCAGTGTGA               GCCTGGCTATGAACTAGAGGGGAACAGGGAACGTGTCTGCCAGGAGAACAGACAGTGGAGTGGAGGGGTG               GCAATATGCAAAGAGACCAGGTGTGAAAACTCCACTTGAATTTCTCAATGGGAAAGCTGACATTGAAACA               GGACGACTGGACCCAACGTGGTATATTCCTGCAACAGAGGCTACAGTCTTGAAGGGCCATCTGAGGCACA               CTGCACAGAAATGGAACCTGGAGCCACCCAGTCCCTCTCTGCAAAAACCAATCCATGCCCTGTTCCTTTT               GTGATTCCCGAGAATGCTCTGCTGTCTGAAAAGGAGTTTTATGTTGATCAGAATGTGTCCATCAAATGTA               GGGAAGGTTTTCTGCTGCAGGGCCACGGCATCATTACCTGCAACCCCGACGAGACGTGGACACAGACAAG               CGCCAAATGTGAAAAAATCTCATGTGGTCCACCAGCTCACGTAGAAAATGCAATTGCTCGAGGCGTACAT               TATCAATATGGAGACATGATCACCTACTCATGTTACAGTGGATACATGTTGGAGGGTTTCCTGAGGAGTG               TTTGTTTAGAAATGGAACATGGACATCACCTCCTATTTGCAGAGCTGTCTGTCGATTTCCATGTCAGAAA               TGGGGGGGCATCTGCCAACGCCCATGCTTGTTCCTGTCCAGAGCGCTGGATGGGGCGCCTCTGTGAAGAA               CCAATCTGCATTCTTCCCTGTCTGAACGGAGGTCGCTQTGTGGCCCCTTACCAGTGTGACTGCCCGCCTG               GCTGGACGGGGTCTCGCTGTCATACAGCTGTTTGCCAGTCTCCCTGCTTAATGGTGGAAAAATGTGTAAG               ACCAACCGATGTCACTGTCTTTCTTCTTGGACGGGAAAATAACTGTTCCAGGAAAAGGAGGACTGGGTTT                 TAA   CCACTGCACGACCATCTGGCTCTCCCAAAAGCAGGATCATCTCTCCTCGGTAGTGCCTGGGCATCCT                   GGAACTTATGCAAAGAAAGTCCAACATGGTGCTGGGTCTTGTTTAGTAAACTTGTTACTTGGGGTTACTT                   TTTTTATTTTGTGATATATTTTGTTATTCCTTGTGACATACTTTCTTACATGTTTCAATTTTTAAATATG                   CCTGTATTTTCTATATAAAAATTATATTAAATAGATGCTGCTCTACCCTCACAAAATGTACATATTCTGC                   TGTCTATTGGGAAGTTCCTGGTACACATTTTTATTCAGTTACTTAAAATGATTTTTCCATTAAAAGTATA                   TTTTGCTACTAAATAAAAAAAA                    
 
       [0101] The sequence of NOV2b was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0102] The DNA sequence and protein sequence for a novel polydom-like gene were obtained by SeqCallingTM Technology and are reported here as NOV2b. These methods used to amplify NOV2b cDNA are described in the Example 2.  
       [0103] The NOV2b polypeptide (SEQ ID NO: 8) encoded by SEQ ID NO: 7 is 3568 amino acid residues in length and is presented using the one-letter amino acid code in Table 2D. The SignalP, Psort and/or Hydropathy results predict that NOV2b has a signal peptide and is likely to be localized extracellularly with a certainty of 0.3846. In alternative embodiments, a NOV2b polypeptide is located to the lysosome (lumen) with a certainty of 0.1900, the endoplasmic reticulum (membrane) with a certainty of 0.1000, or the endoplasmic reticulum (lumen) with a certainty of 0.1000. The SignalP predicts a likely cleavage site for a NOV2b peptide between amino acid positions 16 and 17, i.e. at the dash in the sequence VSG-WA.  
               TABLE 2D                       Encoded NOV2b Protein Sequence                                        (SEQ ID NO:8)                         MRRICAACWGLALVSGWATFQQMSPSRNFSFRLFPETAPGAPGSIPAPPAPGDEAAGSRVERLGQAFRVRLLRELS                   ERLELVFLVDDSSSVGEVNFRSELMFVRKLLSDFPVVPTATRVAIVTFSSKNYVVPRVDYISTRRARQHKCALLLQ               EIPAISYRGGGTYTKGAFQQAAQILLHARENSTKVVFLITDGYSNGGDPRPIAASLRDSGVEIFTFGIWQGNIREL               NDMASTPKEEHCYLLHSFEEFEALARRALHEDLPSGSFIQDDMVHCSYLCDEGKDCCDRMGSCKCGTHTGHFECIC               EKGYYGKGLQYECTACPSGTYKPEASPGGISSCIPCPDENHTSPPGSTSPEDCVCREGYRASGQTCELVHCPALKP               PENGYFIQNTCNNHFNAACGVRCHPGFDLVGSSIILCLPNGLWSGSESYCRVRTCPHLRQPKHGHISCSTREMLYK               TTCLVACDEGYRLEGSDKLTCQGNSQWDGPEPRCVERHCSTFQMPKDVIISPHNCGKQPAKFGTICYVSCRQGFIL               SGVKEMLRCTTSGKWNVGVQAAVCKDVEAPQINCPKDIEAKTLEQQDSANVTWQIPTAKDNSGEKVSVRVHPAFTP               PYLFPIGDVAIVYTATDLSGNQASCIFHIKVIDAEPPVIDWCRSPPPVQVSEKVHAASWDEPQFSDNSGAELVITR               SHTQGDLFPQGETIVQYTATDPSGNNRICDIHIVMKGSPCEIPFTPVNGDFICTPDNTGVNCTLTCLEGYDFTEGS               TDKYYCAYEDGVWKPTYTTEWPDCAKKRFANHGFKSFEMFYKAARCDDSDLMKKFSEAFETTLGKMVPSFCSDAED               IDCRLEENLTKKYCLEYNYDYENGFAIGPGGWGAANRLDYSYDDFLDTVQETATSIGNAKSSRIKRSAPLSDYKIK               LIFNITASVPLPDERNDTLEWENQQRLLQTLETITNKLKRTLNKDPMYSFQLASEILIADSNSLETKKASPFCRPG               SVLRGRMCVNCPLGTYYNLEHFTCESCRIGSYQDEEGQLECKLCPSGMYTEYIHSRNISDCKAQCKQGTYSYSGLE               TCESCPLGTYQPKFGSRSCLSCPENTSTVKRGAVNISACGVPCPEGKFSRSGLMPCHPCPRDYYQPNAGKAFCLAC               PFYGTTPFAGSRSITECSSFSSTFSAAEESVVPPASLGHIKKRHEISSQASHECFFNPCHNSGTCQQLGRGYVCLC               PLGYTGLKCETDIDECSPLPCLNNGVCKDLVGEFICECPSGYTGKHCELNINECQSNPCRNQATCVDELNSYSCKC               QPGFSGKRCETGMYQLSVINNLNNAVCEDQVGGFLCKCPPGFLGTRCGKNVDECLSQPCKNGATCKDGANSFRCLC               AAGFTGSHCELNINECQSNPCRNQATCVDELNSYSCKCQPGFSGKRCETEQSTGFNLDFEVSGIYGYVMLDGMLPS               LHALTCTFWMKSSDDMNYGTPISYAVDNGSDNTLLLTDYNGWVLYVNGREKITNCPSVNDGRWHHIAITWTSTGGA               WRVYINGELSDGGTGLSIGKAIPGGGALVLGQEQDKKGEGFNPAESFVGSISQLNLWDYVLSPQQVKSLATSCPEE               LSKGNVLAWPDFLSGIVGKVKIDSKSIFCSDCPRLGGSVPHLRTASEDLKPGSKVNLFCEPGFQLVGNPVQYCLNQ               GQWTQPLPHCERIRCGVPPPLENGFHSADDFYAGSTVTYQCNNGYYLLGDSRMFCTDNGSWNGVSPSCLDVDECAV               GSDCSEHASCLNVDGSYICSCVPPYTGDGKNCAEPIKCKAPGNPENGHSSGEIYTVGAEVTFSCQEGYQLMGVTKI               TCLESGEWNHLIPYCKAVSCGKPAIPENGCIEELAFTFGSKVTYRCNKGYTLAGDKESSCLANSSWSHSPPVCEPV               KCSSPENINNGKYILSGLTYLSTASYSCDTGYSLQGPSIIECTASGIWDRAPPACHLVFCGEPPAIKDAVITGNNF               TFRNTVTYTCKEGYTLAGLDTIECLADGKWSRSDQQCLAVSCDEPPIVDHASPETAHRLFGDIAFYYCSDGYSLAD               NSQLLCNAQGKWVPPEGQDMPRCIAHFCEKPPSVSYSILESVSKAKFAAGSVVSFKCMEGFVLNTSAKIECMRGGQ               WNPSPMSIQCIPVRCGEPPSIMNGYASGSNYSFGAMVAYSCNKGFYIKGEKKSTCEATGQWSSPIPTCHPVSCGEP               PKVENGFLEHTTGRIFESEVRYQCNPGYKSVGSPVFVCQANRHWHSESPLMCVPLDCGKPPPIQNGFMKGENFEVG               SKVQFFCNEGYELVGDSSWTCQKSGKWNKKSNPKCMPAKCPEPPLLENQLVLKELTTEVGVVTFSCKEGHVLQGPS               VLKCLPSQQWNDSFPVCKIVLCTPPPLISFGVPIPSSALHFGSTVKYSCVGGFFLRGNSTTLCQPDGTWSSPLPEC               VPVECPQPEEIPNGIIDVQGLAYLSTALYTCKPGFELVGNTTTLCGENGHWLGGKPTCKAIECLKPKEILNGKFSY               TDLHYGQTVTYSCNRGFRLEGPSALTCLETGDWDVDAPSCNAIHCDSPQPIENGFVEGADYSYGAIIIYSCFPGFQ               VAGHAMQTCEESGWSSSIPTCMPIDCGLPPHIDFGDCTKLKDDQGYFEQEDDMMEVPYVTPHPPYHLGAVAKTWEN               TKESPATHSSNFLYGTMVSYTCNPGYELLGNPVLICQEDGTWNGSAPSCISIECDLPTAPENGFLRFTETSMGSAV               QYSCKPGHILAGSDLRLCLENRKWSGASPRCEAISCKKPNPVMNGSIKGSNYTYLSTLYYECDPGYVLNGTERRTC               QDDKNWDEDEPICIPVDCSSPPVSANGQVRGDEYTFQKEIEYTCNEGFLLEGARSRVCLANGSWSGATPDCVPVRC               ATPPQLANGVTEGLDYGFMKEVTFHCHEGYILHGAPKLTCQSDGNWDAEIPLCKPVNCGPPEDLAHGFPNGFSFIH               GGHIQYQCFPGYKLHGNSSRRCLSNGSWSGSSPSCLPCRCSTPVIEYGTVNGTDFDCGKAARIQCFKGFKLLGLSE               ITCEADGQWSSGFPHCEHTSCGSLPMIPNAFISETSSWKENVITYSCRSGYVIQGSSDLICTEKGVWSQPYPVCEP               LSCGSPPSVANAVATGEAHTYESEVKLRCLEGYTMDTDTDTFTCQKDGRWFPERISCSPKKCPLPENITHILVHGD               DFSVNRQVSVSCAEGYTFEGVNISVCQLDGTWEPPFSDESCSPVSCGKPESPEHGFVVGSKYTFESTIIYQCEPGY               ELEGNRERVCQENRQWSGGVAICKETRCETPLEFLNGKADIENRTTGPNVVYSCNRGYSLEGPSEAHCTENGTWSH               PVPLCKPNPCPVPFVIPENALLSEKEFYVDQNVSIKCREGFLLQGHGIITCNPDETWTQTSAKCEKISCGPPAHVE               NAIARGVHYQYGDMITYSCYSGYMLEGFLRSVCLENGTWTSPPICRAVCRFPCQNGGICQRPNACSCPEGWMGRLC               EEPICILPCLNGGRCVAPYQCDCPPGWTGSRCHTAVCQSPCLNGGKCVRPNRCHCLSSWTGHNCSRKRRTGF                  
 
       [0104] SNP variants of NOV2 are disclosed in Example 3.  
       [0105] NOV2 Clones  
       [0106] Unless specifically addressed as NOV2a or NOV2b, any reference to NOV2 is assumed to encompass all variants.  
       [0107] The amino acid sequence of NOV2 has high homolgy to other proteins as shown in Table 2E.  
               TABLE 2E                          BLASTX Results from Patp Database for NOV2                                 Smallest           High   Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P (N)                                     patp: AAM93954   Human polypeptide,   8375   0.0       patp: AAB94754   Human protein sequence   7012   0.0       patp: AAU16963   Human novel secreted protein   6452   0.0       patp: AAU18126   Novel human uterine motility-association po . . .   6452   0.0       patp: AAG66398   Receptor 222 - Unidentified   5577   0.0                  
 
       [0108] In a search of sequence databases, it was found, for example, that the NOV2a nucleic acid sequence has 2414 of 2422 bases (99%) identical to a gb:GENBANK-ID:HST000009|acc:AL079279.1 mRNA from  Homo sapiens  ( Homo sapiens  mRNA full length insert cDNA clone EUROIMAGE 248114). Further, the full amino acid sequence of the disclosed NOV2a protein of the invention has 2895 of 3567 amino acid residues (81%) identical to, and 3181 of 3567 amino acid residues (89%) similar to, the 3567 amino acid residue ptnr:TREMBLNEW-ACC:AAG32160 protein from  Mus musculus  (Mouse) (POLYDOM PROTEIN PRECURSOR).  
       [0109] In a similar search of sequence databases, it was found, for example, that the NOV2b nucleic acid sequence has 7556 of 9127 bases (82%) identical to a gb:GENBANK-ID:AF206329|acc:AF206329.1 mRNA from  Mus musculus  ( Mus musculus  polydom protein mRNA, complete cds). Further, the full amino acid sequence of the disclosed NOV2b protein of the invention has 2902 of 3565 amino acid residues (81%) identical to, and 3189 of 3565 amino acid residues (89%) similar to, the 3567 amino acid residue ptnr:SPTREMBL-ACC:Q9ES77 protein from  Mus musculus  (Mouse) (POLYDOM PROTEIN PRECURSOR).  
       [0110] Additional BLASTP results are shown in Table 2F.  
               TABLE 2F                          NOV2 BLASTP Results                                     Gene Index/       Length of   Identity   Positives   Expect       Identifier   Protein/Organism   aa   (%)   (%)   Value                                             Q9ES77   POLYDOM PROTEIN   3567    289/3567   3181/3567   0.0           PRECURSOR -       (81%)   (89%)             Mus musculus  (Mouse)       BAB55420   CDNA FLJ14964 FIS,   1316   1255/1316   1267/1316   0.0           CLONE PLACE4000581,       (95%)   (96%)           MODERATELY SIMILAR           TO FIBROPELLIN I           PRECURSOR -             Homo sapiens  (Human)       AAH08135   POLYDOMAIN PROTEIN -   669    534/668    594/668   0.0             Mus musculus  (Mouse)       (79%)   (88%0       Q9CUT3   4833413O10RIK PROTEIN -   601    483/601    538/601   2.4e−298             Mus musculus  (Mouse)       (80%)   (89%)       Q9H284   SEROLOGICALLY   481    458/482    462/482   1.8e−261           DEFINED BREAST       (95%)   (95%)           CANCER ANTIGEN NY-           BR-38 -  Homo sapiens             (Human)                  
 
       [0111] A multiple sequence alignment is given in Table 2G, with the NOV2 protein of the invention being shown in lines 1 and 2, in a ClustalW analysis comparing NOV2 with related protien sequences of Table 2F. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       [0112] Domain results for NOV2 were collected from the Pfam database, and then identified by the Interpro domain accession number. The results are listed in Table 2H with the statistics and domain description. These results indicatee that the NOV2 polypeptides have properties similar to those of other proteins known to contain these domains.  
                   TABLE 2H                          Domain Analysis of NOV2                                     Score   E           PSSMs Producing Significant Alignments   (bits)   Value               Von Willebrand Factor Type A (vwa): domain 1 of 1, from   86.8   4.5e−22           from 80 to 256                                     vwa   DivFLlDGSgSigsqnFervKdFvervverLdvgprdkkeedavrVg   (SEQ ID NO:52)               +++||+| |+|+&#39;0 + +|   + |++++ +++ + + +      ++|+       NOV2a   ELVFLVDDSSSVGEVNFRSELMFVRKLLSDFPVVP-TA-----TRVA   (SEQ ID NO:6)                   lvQYSdnvrtEikfklndyqnk........devlqalqkiryedyygggg           ++++|++  +   ++  ++ + ++ ++++ + +++ + ++     + +++       NOV2a   IVTFSSKNYV---VPRVDYISTrrarqhkcALLLQEIPAIS----YRGGG                   tnTgaALqyvvrnlfteasGsRiepvaeegapkvlVvlTDGrsqddpspT           + | +| + ++  + +    +|      ++ ++++ ++||| ++++       NOV2a   TYTKGAFQQAAQILLH----AR------ENSTKVVFLITDGYSNGG----                   idirdvlnelkkeagvevfaiGvGnadnnnleeLreIAskpd.dhvfkvs            + + +++++++  +++++++|+ +  +   ++|+ +|+ + +++ + ++       NOV2a   -DPRPIAASLRD-SGVEIFTFGIWQG-N--IRELNDMASTPKeEHCYLLH                   dfeaLdtlqelL           ++++ + ++++       NOV2a   SFEEFEALVALC                                         pentaxin: domain 1 of 1, from 1469 to 1607   75.5   7.5e−21                                     Pentaxin   SYaTkkPlkDNElLifkekdgqYslyvggaPqLevtfkvkeefvaPv   (SEQ ID NO:53)               ||++ +   || +|+     ++  +++++    +++   +   + ++       NOV2a   SYAVDN-GSDNTLLL--TDYNGWVLYVNGR--EKITNCPSVNDGRWH   (SEQ ID NO:6)                   HiCtSWeSssGiaEfWVDGkhCpwvrkglkkGytvgaepsIiLGQEQDSy           |+  +| |  |     ++|       +++  |  +  ++  +||||||       NOV2a   HIAITWTSTGGAWRVYINGE-LSDGGTGLSIGKAIPGGGALVLGQEQDKK                   GGgFdksQSlVGEigdlnMWDyVLtPeeIktvykgagplerhiypNILdw           | +|+   |+|| ++ +++||+||+|++++++     + +    +|+| |       NOV2a   GEGFNPAESFVGSISQLNLWDYVLSPQQVKSLATS-CPEE-LSKGNVLAW                                         sushi: domain 13 of 34, from 2145 to 2198   73.7   3.8e−18                                     sushi   Cp.pPdieNGrvsssgtyeypvGdtvtytCneGYrlvGsssitCted   (SEQ ID NO:54)               |+++| ++||+ + + ++++  |  + ++|++|++++|++ ++| ++       NOV2a   CGePPSIMNGYASGS-NYSF--GAMVAYSCNKGFYIKGEKKSTCEAT   (SEQ ID NO:6)                   ggGgWsppllGelPkC             |+|++++    |+|       NOV2a   --GQWSSPI----PTC                  
 
       [0113] The NOV2 disclosed in this invention is expressed in at least the following tissues: adipose, adrenal gland, bone marrow, brain—amygdala, brain—cerebellum, brain—hippocampus, brain—substantia nigra, brain—thalamus, brain—whole, fetal brain, fetal kidney, liver, lung, heart, kidney, ascending colon, lymphoma—Raji, mammary gland/breast, pancreas, nasoepithelium, pituitary gland, placenta, prostate, cervix, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus. This information was derived by determining the tissue sources of the sequences that were included in the invention including but not limited to SeqCalling sources, Public EST sources, Literature sources, and/or RACE sources.  
       [0114] The protein similarity information, expression pattern, and map location for the Polydom-like protein and nucleic acid disclosed herein suggest that this Polydom may have important structural and/or physiological functions characteristic of the epidermal growth factor (EGF) family. Therefore, the nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, the compositions of the presnet invention will have efficacy for treatment of patients suffering from: cancers, congenital heart disease, inflammatory disorders, erythroid-megakaryocytic leukaemia, Vacuoliting megalencephalic leukoencephalopathy, chronic contact dermatitis, fibrosarcoma, wound healing, neoplasia, such as T-cell acute lymphoblastic leukemia/lymphoma, reproductive disorders, fetal arrhythmias, immune system disorders, disorders of coagulation, obesity, diabetes, asthma, arthritis, osteoporosis, and other diseases, disorders and conditions of the like.  
       [0115] The novel nucleic acid encoding the polydom-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV2 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV2 epitope is from about amino acids 0 to 125. In another embodiment, a contemplated NOV2 epitope is from about amino acids 130 to 250. In other specific embodiments, contemplated NOV2 epitopes are from about amino acids 250 to 3600.  
       [0116] NOV3  
       [0117] Another NOVX protein of the invention, referred to herein as NOV3, includes two novel transmembrane/IIIb-like protein. The disclosed proteins have been named NOV3a and NOV3b. The NOV3a and NOV3b proteins of the invention cause growth inhibition of  E. coli  when expressed exogenously.  
       [0118] The NOV3a and NOV3b protein predicted here are localized extracellularly. Therefore, it is likely that they are accessible to a diagnostic probe, and for the various therapeutic applications described herein.  
       [0119] At least the NOV3b transmembrane-like protein disclosed in this invention maps to chromosome 20. This information was assigned using OMIM, the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0120] NOV3a  
       [0121] In one embodiment, a NOV3 variant is NOV3 a (alternatively referred to herein as CG50273-01), which encodes a novel transmembrane-like protein and includes the 870 nucleotide sequence (SEQ ID NO: 9) shown in Table 3A. An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 1-3 and ending with a TAA codon at nucleotides 628-630. Putative untranslated regions downstream from the termination codon and upstream from the initiation codon are underlined in Table 3A, and the start and stop codons are in bold letters.  
               TABLE 3A                       NOV3a Nucleotide Sequence                                        (SEQ ID NO:9)                           ATG GGCTCCTGCTCCGGCCGCTGCGCGCTCGTCGTCCTCTGCGCTTTTCAGCTGGTGGTCGCCGCCCTGGAGAGGC                   AGGTGTTTGACTTCCTGGGCTACCAGTGGGCGCCCATCCTGGCCAACTTTGTCCACATCATCATCGTCATCCTGGG               ACTCTTCGGCACCATCCAGTACCGGCTGCGCTATGTCATGGTGTACACGCTGTGGGCAGCCGTCTGGGTCACCTGG               AACGTCTTCATCATCTGCTTCTACCTGGAAGTCGGTGGCCTCTTAAAGGACAGCGAGCTACTGACCTTCAGCCTCT               CCCGGCATCGCTCCTGGTGGCGTGAGCGCTGGCCAGGCTGTCTGCATGAGGAGGTGCCAGCAGTGGGCCTCGGGGC               CCCCCATGGCCAGGCCCTGGTGTCAGGTGCTGGCTGTGCCCTGGAGCCCAGCTATGTGGAGGCCCTACACAGTTGC               CTGCAGATCCTGATCGCGCTTCTGGGCTTTGTCTGTGGCTGCCAGGTGGTCAGCGTGTTTACGGAGGAAGAGGACA               GCTTTGATTTCATTGGTGGATTTGATCCATTTCCTCTCTACCATGTCAATGAAAAGCCATCCAGTCTCTTGTCCAA               GCAGGTGTACTTGCCTGCG TAA   GTGAGGAAACAGCTGATCCTGCTCCTGTGGCCTCCAGCCTTCAGCGACCGACCA                   GTGACAATGACAGGAGCTCCCAGGCCTTGGGACGCGCCCCCACCCAGCACCCCCCAGGCGGCCGGCAGCACCTGCC                   CTGGGTTTTAAGTACTGGACACCAGCCAGGGCGGCAGGGCAGTGCCACGGCTGGCTGCAGCGTCAAGAGAGTTTGT                   AATTTCCTTTCTCTTAAAAAAAAAAAAAAAAAAA                    
 
       [0122] The sequence of NOV3a was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0123] The DNA sequence and protein sequence for a novel transmembrane-like gene were obtained by SeqCallingTM Technology and are reported here as NOV3a. These methods used to amplify NOV3a cDNA are described in Example 2.  
       [0124] The NOV3a polypeptide (SEQ ID NO: 10) encoded by SEQ ID NO: 9 is 209 amino acid residues in length and is presented using the one-letter amino acid code in Table 3B. The SignalP, Psort and/or Hydropathy results predict that NOV3a has a signal peptide and is likely to be localized extracellularly at the plasma membrane with a certainty of 0.4600. In alternative embodiments, a NOV3a polypeptide is located to the microbody (peroxisome) with a certainty of 0.1026, the endoplasmic reticulum (membrane) with a certainty of 0.1000, or the endoplasmic reticulum (lumen) with a certainty of 0.1000. The SignalP predicts a likely cleavage site for a NOV3a peptide between amino acid positions 29 and 30, i.e. at the dash in the sequence GAG-VL.  
               TABLE 3B                       Encoded NOV3a Protein Sequence                                        (SEQ ID NO:10)                         MGSCSGRCALVVLCAFQLVVAALERQVFDFLGYQWAPILANFVHIIIVILGLFGTIQYRLRYVMVYTLWAAVWVTW                   NVFIICFYLEVGGLLKDSELLTFSLSRHRSWWRERWPGCLHEEVPAVGLGAPHGQALVSGAGCALEPSYVEALHSC               LQILIALLGFVCGCQVVSVFTEEEDSFDFIGGFDPFPLYHVNEKPSSLLSKQVYLPA                  
 
       [0125] NOV3b  
       [0126] In an alternative embodiment, a NOV3 variant is NOV3b (alternatively referred to herein as CG50273-02), which includes the 632 nucleotide sequence (SEQ ID NO: 11) shown in Table 3C. An open reading frame for the mature protein was identified beginning with an GTC codon at nucleotides 2-4 and ending with a TAA codon at nucleotides 593-595. The start and stop codons of the open reading frame are highlighted in bold type. Putative untranslated regions are underlined and found upstream from the initiation codon and downstream from the termination codon.  
               TABLE 3C                       NOV3b Nucleotide Sequence                                        (SEQ ID NO:11)                           C   GT CCTCTGCGCTTTTCAGCTGGTCGCCGCCCTGGAGAGGCAGGTGTTTGACTTCCTGGGCTACCAGTGGGCGCC                   CATCCTGGCCAACTTTGTCCACATCATCATCGTCATCCTGGGACTCTTCGGCACCATCCAGTACCGGCTGCGCTA               TGTCATGGTGTACACGCTGTGGGCAGCCGTCTGGGTCACCTGGAACGTCTTCATCATCTGCTTCTACCTGGAAGT               CGGTGGCCTCTTAAAGGACAGCGAGCTACTGACCTTCAGCCTCTCCCGGCATCGCTCCTGGTGGCGTGAGCGCTG               GCCAGGCTGTCTGCATGAGGAGGTGCCAGCAGTGGGCCTCGGGGCCCCCCATGGCCAGGCCCTGGTGTCAGGTGC               TGGCTGTGCCCTGGAGCCCAGCTATGTGGAGGCCCTACACAGTTGCCTGCAGATCCTGATCGCGCTTCTGGGCTT               TGTCTGTGGCTGCCAGGTGGTCAGCGTGTTTACGGAGGAAGAGGACAGCTTTGATTTCATTGGTGGATTTGATCC               ATTTCCTCTCTACCATGTCAATGAAAAGCCATCCAGTCTCTTGTCCAAGCAGGTGTACTTGCCTGCG TAA   GTGAG                   GAAACAGCTGATCCTGCTCCTGTGGCCTCCAC                    
 
       [0127] The sequence of NOV3b was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0128] The cDNA coding for the NOV3b sequence was cloned by the polymerase chain reaction (PCR). Primers were designed based on in silico predictions of the full length or some portion (one or more exons) of the cDNA/protein sequence of the invention, or by translated homology of the predicted exons to closely related human sequences or to sequences from other species. The DNA sequence and protein sequence for a novel transmembrane-like gene were obtyained by exon linking and are reported here as NOV3b. These primers and methods used to amplify NOV3b cDNA are described in Example 2.  
       [0129] The NOV3b polypeptide (SEQ ID NO: 12) encoded by SEQ ID NO: 11 is 197 amino acid residues in length and is presented using the one-letter amino acid code in Table 3D. The SignalP, Psort and/or Hydropathy results predict that NOV3b has a signal peptide and is likely to be localized in the membrane of the endoplasmic reticulum with a certainty of 0.6850. In alternative embodiments, a NOV3b polypeptide is located to the plasma membrane with a certainty of 0.6400, the Golgi body with a certainty of 0.4600, or the endoplasmic reticulum (lumen) with a certainty of 0.1000. The SignalP predicts a likely cleavage site for a NOV3b peptide between amino acid positions 13 and 14, i.e. at the dash in the sequence LER-QV.  
               TABLE 3D                       Encoded NOV3b Protein Sequence                                        (SEQ ID NO:12)                         VLCAFQLVAALERQVFDFLGYQWAPILANFVHIIIVILGLFGTIQYRLRYVMVYTLWAAVWVTWNVFIICFYLEVG                   GLLKDSELLTFSLSRHRSWWRERWPGCLHEEVPAVGLGAPHGQALVSGAGCALEPSYVEALHSCLQILIALLGFVC               GCQVVSVFTEEEDSFDFIGGFDPFPLYHVNEKPSSLLSKQVYLPA                  
 
       [0130] SNP variants of NOV3 are disclosed in Example 3.  
       [0131] NOV3 Clones  
       [0132] Unless specifically addressed as NOV3a or NOV3b, any reference to NOV3 is assumed to encompass all variants.  
       [0133] The amino acid sequence of NOV3 has high homolgy to other proteins as shown in Table 3E.  
               TABLE 3E                          BLASTX Results from Patp Database for NOV3                                 Smallest           High   Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P                                     patp: AAB62810   Human nervous system associated protein NSPRT3   1092     2.3e−110       patp: AAY94954   Human secreted protein clone iw66_1   619   3.0e−60       patp: AAG78000   Human actin 14   466   4.9e−44       patp: AAB94211   Human protein sequence   425   1.1e−39       patp: AAB25811   Human secreted protein   317   3.0e−28                  
 
       [0134] In a search of sequence databases, it was found, for example, that the NOV3a nucleic acid sequence has 572 of 704 bases (81%) identical to a gb:GENBANK-ID:AB030182|acc:AB030182.1 mRNA from  Mus musculus  ( Mus musculus  mRNA, complete cds, clone:1-107). Further, the full amino acid sequence of the protein of the disclosed NOV3a protein of the invention has 173 of 209 amino acid residues (82%) identical to, and 182 of 209 amino acid residues (87%) similar to, the 208 amino acid residue ptnr:SPTREMBL-ACC:Q9JMG4 protein from  Mus musculus  (Mouse) (MRNA, COMPLETE CDS, CLONE:1-107).  
       [0135] In a similar search of sequence databases, it was found, for example, that the NOV3b nucleic acid sequence has 514 of 618 bases (83%) identical to a gb:GENBANK-ID:ABO30182|acc:AB030182.1 mRNA from  Mus musculus  ( Mus musculus  mRNA, complete cds, clone: 1-107). Further, the full amino acid sequence of the disclosed NOV3b protein of the invention has 165 of 196 amino acid residues (84%) identical to, and 173 of 196 amino acid residues (88%) similar to, the 208 amino acid residue ptnr:SPTREMBL-ACC:Q9JMG4 protein from  Mus musculus  (Mouse) (MRNA, COMPLETE CDS, CLONE:1-107).  
       [0136] Additional BLASTP results are shown in Table 3F.  
               TABLE 3F                          NOV3 BLASTP Results                                     Gene Index/       Length of   Identity   Positives   Expect       Identifier   Protein/Organism   aa   (%)   (%)   Value               Q9BQU8   BA261N11.2.1 (NOVEL   207   207/209   207/209    1.4e−110           PROTEIN, ISOFORM 1) -       (99%)   (99%)             Homo sapiens         Q9JMG4   MRNA, COMPLETE CDS,   208   173/209   182/209   1.0e−91           CLONE: 1-107       (82%)   (87%)           (C030019F02RIK           PROTEIN) -  Mus musculus             (Mouse)       Q9D8W0   C030019F02RIK PROTEIN -   208   172/209   181/209   3.5e−91             Mus musculus  (Mouse)       (82%)   (86%)       Q9D1V9   C030019F02RIK PROTEIN -   208   172/209   181/209   3.5e−91             Mus musculus  (Mouse)       (82%)   (86%)       Q9D0Q6   2610200G18RIK PROTEIN -   207   120/206   144/206   8.0e−60             Mus musculus  (Mouse)       (58%)   (69%)                  
 
       [0137] A multiple sequence alignment is given in Table 3G, with the NOV3 protein of the invention being shown in lines 1 and 2, in a ClustalW analysis comparing NOV3 with related protien sequences of Table 3F. 
 
 
 
       [0138] In a search of the Pfam database, there were no known domain results for NOV3.  
       [0139] The NOV3 disclosed in this invention is expressed in at least the following tissues: bone marrow, brain—substantia nigra, brain—temporal lobe, brain—whole, heart, kidney, pancreas, astrocytoma, CNS, multiple sclerosis lesions, and uterus. This information was derived by determining the tissue sources of the sequences that were included in the invention including but not limited to SeqCalling sources, Public EST sources, Literature sources, and/or RACE sources.  
       [0140] The protein similarity information, expression pattern, and map location for the transmembrane-like protein and nucleic acid disclosed herein suggest that this protein may have important structural and/or physiological functions characteristic of the transmembrane family. Therefore, the nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, the compositions of the present invention will have efficacy for treatment of patients suffering from: cancer, trauma, regeneration (in vitro and in vivo), viral/bacterial/parasitic infections, neuroprotection, Von Hippel-Lindau (VHL) syndrome, Alzheimer&#39;s disease, stroke, tuberous sclerosis, hypercalceimia, Parkinson&#39;s disease, Huntington&#39;s disease, cerebral palsy, epilepsy, Lesch-Nyhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain and other diseases, disorders and conditions of the like.  
       [0141] The novel nucleic acid encoding the transmembrane-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV3 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV3 epitope is from about amino acids 85 to 130. In another embodiment, a contemplated NOV3 epitope is from about amino acids 165 to 210.  
       [0142] NOV4  
       [0143] Still another NOVX protein of the invention, referred to herein as NOV4 (alternatively referred to as CG50289-01), is a serine protease-like protein.  
       [0144] Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Over 20 families of serine protease have been identified and although they have different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C clans have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base. The geometric orientations of the catalytic residues are similar between families, despite different protein folds. The enzymes are inherently secreted, being synthesised with a signal peptide that targets them to the secretory pathway. Animal enzymes are either secreted directly, packaged into vesicles for regulated secretion, or are retained in leukocyte granules.  
       [0145] Although SignalP, Psort and/or hydropathy suggest that the Serine Protease-like protein may be localized at the plasma membrane, the protein predicted here is similar to the Serine Protease family, some members of which are secreted. Therefore it is likely that this novel Serine Protease-like protein is available at the same sub-cellular localization and hence accessible to a diagnostic probe and for various therapeutic applications.  
       [0146] The NOV4 nucleic acid and polypeptide described in this application has a structure similar to Testicular Serine Protease-1 (TESP-1) and TESP-2, serine proteases isolated from the mouse sperm acrosome. These proteins may play a role in fertilization and/or processing of other proteins during fertilization.  
       [0147] The NOV4 protein disclosed in this invention maps to chromosome 2. This information was assigned using OMIM, the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0148] The NOV4 nucleic acid (SEQ ID NO: 13) of 909 nucleotides encodes a novel serine protease-like protein and is shown in Table 4A. An open reading frame for the mature protein was identified beginning with a ATG initiation codon at nucleotides 14-16 and ending with a TGA codon at nucleotides 899-901. Putative untranslated regions upstream from the start codon and downstream from the termination codon are underlined in Table 4A. The start and stop codons are in bold letters.  
               TABLE 4A                       NOV4 Nucleotide Sequence                                        (SEQ ID NO:13)                           GGCCACCGGCCTG   ATG AGGGAAGCAGGGGCAGAGCGCTCAGGCCAGCCGGCGGGGGCACTGCGCACTGGCCGCCTC                   CCTCCTCTGGCCAATCCTCCTGCCGCTGCGCGTCTAGTCCACCTCGTCCCTCTCTGCAGGTCCACTAACCCATCTG               ATTACCGGATCCTGCTTGGGTATGACCAGCAAAGCCATCCCACAGAGCACAGCAAGCAGATGACAGTGAATAAGAT               CATGGTGCACGCTGACTATAACGAGTTGCACCGCATGGGGAGTGACATCACCCTGCTGCAGCTGCACCGTCATGTG               GAATTCAGCTCCCACATCCTCCCCGCCTGCCTTCCGGAACCAACCACGTGGCTGGCCCCTGACAGCTCCTGCTGGA               TATCTGGTTGGGGAATGGTCACCGAGGATGTCTTCCTGCCTGAGCCCTTCCAACTTCAGGAGGCAGAGGTCGGTGT               CATGGACAACACTGTCTGCGGATCCTTTTTCCAGCCCCAGTACCCCGGCCAGCCAAGCAGCAGTGACTACACCATC               CACGAGGACATGCTGTGCGCTGGGGACCTCATAACAGGAAAGGCCATTTGCCGACGAGACTCCAGGGGTCCCCTCG               TCTGCCCATTAAATGGCACCTGGTTCCTGATGGGGCTGTCTAGTTGGAGCCTCGACTGCTGCTCACCCGTCGGTCC               CAGGGTCTTCACCAGGCTCCCCTACTTCACCAACTGGATCAGCCAGAAGAAGAGGGAGAGCACCCCTCCAGATCCC               GCCTTGGCTCCTCCTCAGGAAACACCCCCAGCCCTGGACAGCATGACCTCTCAGGGCATCGTCCACAAGCCCGGGC               TCTGCGCAGCCCTTCTGGCTGCTCACATGTTCCTCCTGCTGCTGATTCTCCTGGGGAGCCTG TGA   AGGGCCAG                    
 
       [0149] The sequence of NOV4 was derived by laboratory cloning of cDNA fragments covering the full length and/or part of the DNA sequence of the invention, and/or by in silico prediction of the full length and/or part of the DNA sequence of the invention from public human sequence databases.  
       [0150] The DNA sequence and protein sequence for a novel polydom-like gene were obtained by SeqCallingTM Technology and are reported here as NOV4. These methods used to amplify NOV4 cDNA are described in Example 2.  
       [0151] The NOV4 polypeptide (SEQ ID NO: 14) encoded by SEQ ID NO: 13 is 295 amino acid residues in length and is presented using the one-letter amino acid code in Table 4B. The SignalP, Psort and/or Hydropathy results predict that NOV4 has no known signal peptide and is likely to be localized in the endoplasmic reticulum membrane with a certainty of 0.8500. In alternative embodiments, a NOV4 polypeptide is located to the plasma membrane with a certainty of 0.4400, the microbody (peroxisome) with a certainty of 0.3313, or the mitochondrial inner membrane with a certainty of 0.1000.  
               TABLE 4B                       Encoded NOV4 Protein Sequence                                        (SEQ ID NO:14)                         MREAGAERSGQPAGALRTGRLPPLANPPAAARLVHLVPLCRSTNPSDYRILLGYDQQSHPTEHSKQMTVNKIMVH                   ADYNELHRMGSDITLLQLHRHVEFSSHILPACLPEPTTWLAPDSSCWISGWGMVTEDVFLPEPFQLQEAEVGVMD               NTVCGSFFQPQYPGQPSSSDYTIHEDMLCAGDLITGKAICRRDSRGPLVCPLNGTWFLMGLSSWSLDCCSPVGPR               VFTRLPYFTNWISQKKRESTPPDPALAPPQETPPALDSMTSQGIVHKPGLCAALLAAHMFLLLLILLGSL                  
 
       [0152] SNP variants of NOV4 are disclosed in Example 3.  
       [0153] The amino acid sequence of NOV4 has high homology to other proteins as shown in Table 4C.  
               TABLE 4C                          BLASTX Results from Patp Database for NOV4                                 Smallest           High   Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P (N)                                     patp: AAW64239   Gerbil homologue of mouse mMCP-7 zymogen - Meriones   344   4.2e−31       patp: AAW64240   Human mast cell tryptase II/beta   342   6.8e−31       patp: AAW64241   Human mast cell tryptase III   342   6.8e−31       patp: AAW63175   Human mast cell tryptase II/beta polypeptide   342   68e−31       patp: AAW63176   Human mast cell tryptase III polypeptide   342   6.8e−31                  
 
       [0154] In a search of sequence databases, it was found, for example, that the NOV4 nucleic acid sequence has 583 of 885 bases (65%) identical to a gb:GENBANK-ID:AB0089110|acc:AB008910.1 mRNA from  Mus musculus  ( Mus musculus  mRNA for TESP1, complete cds). Further, the full amino acid sequence of the disclosed NOV4 protein of the invention has 120 of 253 amino acid residues (47%) identical to, and 172 of 253 amino acid residues (67%) similar to, the 367 amino acid residue ptnr:SPTREMBL-ACC:O70169 protein from  Mus musculus  (Mouse) (TESTICULAR SERINE PROTEASE 1 (TESP1)).  
       [0155] Additional BLASTP results are shown in Table 4D.  
               TABLE 4D                          NOV4 BLASTP Results                                     Gene Index/       Length of           Expect       Identifier   Protein/Organism   aa   Identity (%)   Positives (%)   Value               O70169   TESTICULAR SERINE   367   120/253   172/253   2.1e−59           PROTEASE 1 (TESP1) -       (47%)   (67%)             Mus musculus  (Mouse)       O70170   TESTICULAR SERINE   366   120/252   157/252   4.0e−58           PROTEASE 2 (TESP2) -       (47%)   (62%)             Mus musculus  (Mouse)       Q9D9S6   TESTICULAR SERINE   143    69/140    90/140   4.5e−34           PROTEASE 2 -       (49%)   (64%)             Mus musculus  (Mouse)       Q9XSM2   Tryptase 2 precursor (EC   273    72/195   112/195   7.6e−32           3.4.21.59) -       (36%)   (57%)             Ovis aries  (Sheep)       Q9XSM1   TRYPTASE (EC 3.4.21.59) -   273    73/195   112/195   9.7e−32             Ovis aries  (Sheep)       (37%)   (57%)                  
 
       [0156] A multiple sequence alignment is given in Table 4E in a ClustalW analysis comparing NOV4 with related protein sequences disclosed in Table 4D. 
 
 
 
       [0157] Domain results for NOV4 were collected from the Pfam database, and then identified by the Interpro domain accession number. The results are listed in Table 4F with the statistics and domain description. These results indicatee that the NOV4 polypeptide has properties similar to those of other proteins known to contain these domains.  
                   TABLE 4F                          Domain Analysis of NOV4                                     Score   E           PSSMs Producing Significant Alignments   (bits)   Value                                 trypsin: domain 1 of 1, from 42 to 237   119.2   5.3e−37                                     Trypsin   sapassvrVSlsvrlGehnlsltegteqkfdvkktiivHpnynpdt.   (SEQ ID NO:65)               ++ ++++++     +| ++ +++     + ++++ + +| +++   +       N0V4   STNPSDYRI----LLGYDQQSHPTEHSKQMTVNK-IMVHADYNELHr   (SEQ ID NO:14)                   ldngaYdnDiALlkLkspgvtlgdtvrpicLpsassdlpvGttctvsGwG           ++      |+ |++| +  +++++++ +++|+++   +++ ++++++|+|       NOV4   MG-----SDITLLQLHRH-VEFSSHILPACLPEPTTWLAPDSSCWISGWG                   rrptknlg...lsdtLqevvvpvvsretCrsaye..yggt......dDkv              + ++   + + +|++++++++++ +| + +++++++ +++++ +       NOV4   M--VTEDVflpEPFQLQEAEVGVMDNTVCGSFFQpqYPGQpsssdyT---                   efvtdnmiCagal.ggkdaCqGDSGGPLvcsdgnrdgrwelvGivSwGsy             + ++++|++ + +++++|+ || |||+++ +   ++++++|  |++       NOV4   --IHEDMLCAGDLiTGKAICRRDSRGPLVCPLN---GTWFLMGLSSWS-L                   gCargnkPGvytrVssyldWI            | ++  | ++++  ++ +||       NOV4   DCCSPVGPRVFTRLPYFTNWI                  
 
       [0158] The Serine Protease disclosed in this invention is expressed in at least the following tissues: testis. This information was derived by determining the tissue sources of the sequences that were included in the invention.  
       [0159] The protein similarity information, expression pattern, and map location for the serine protease-like protein and nucleic acid disclosed herein suggest that this protein may have important structural and/or physiological functions characteristic of the serine protease family. Therefore, the NOV4 nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, the compositions of the present invention will have efficacy for treatment of patients suffering from: cancer, trauma, regeneration (in vitro and in vivo), viral/bacterial/parasitic infections, infertility and other diseases, disorders and conditions of the like.  
       [0160] The novel nucleic acid encoding the serine protease-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV4 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV4 epitope is from about amino acids 10 to 30. In another embodiment, a contemplated NOV4 epitope is from about amino acids 35 to 40. In other specific embodiments, contemplated NOV4 epitopes are from about amino acids 45 to 90, 105 to 112, 115 to 120, 127 to 145, 152 to 180, 180 to 195, and 225 to 265.  
       [0161] NOV5  
       [0162] A further NOVX protein of the invention, referred to herein as NOV5, includes two novel Wnt-7a-like proteins. The disclosed proteins have been named NOV5a and NOV5b.  
       [0163] Wnt proteins constitute a large family of molecules involved in cell proliferation, cell differentiation and embryonic patterning. They are known to interact with the Frizzled family of receptors to activate two main intracellular signaling pathways regulating intracellular calcium levels and gene transcription. Wnts play a role in cell proliferation and tumorigenesis, and are also involved in processes involved in mammary gland development and cancer. Furthermore, Wnts are critical to organogenesis of several systems, such as the kidney and brain. Wnts regulate the early development, i.e. neural induction, and their role persists in later stages of development as well as in the mature organ.  
       [0164] The NOV5 proteins predicted here are localized extracellularly. Therefore, it is likely that these Wnt-7a-like proteins are accessible to a diagnostic probe, and for the various therapeutic applications described herein.  
       [0165] At least the NOV5a protein disclosed in this invention maps to chromosome 3. This information was assigned using the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0166] NOV5a  
       [0167] In one embodiment, a NOV5 variant is NOV5a (alternatively referred to herein as CG50353-01), which encodes a novel Wnt-7a-like protein and includes the 1628 nucleotide sequence (SEQ ID NO: 15) shown in Table 5A. An open reading frame for the mature protein was identified beginning with a ATG initiation codon at nucleotides 1-3 and ending with a TGA codon at nucleotides 1048-1050. Putative untranslated regions upstream from the start codon and downstream from the termination codon are underlined in Table 5A. The start and stop codons are in bold letters.  
               TABLE 5A                       NOV5a Nucleotide Sequence                                        (SEQ ID NO:15)                           ATG AACCGGAAAGCGCGGCGCTGCCTGGGCCACCTCTTTCTCAGCCTGGGCATGGTCTGTCTCCTAGCATGTGGC                   TTCTCCTCAGTGGTAGCTCTGGGCGCAACGGTCATCTGTAACAAGATCCCAGGCCTGGCTCCCAGACAGCGGGCG               ATCTGCCAGAGCCGGCCCGACGCCATCATCGTCATAGGAGAAGGCTCACAAATGGGCCTGGACGAGTGTCAGTTT               CAGTTCCGCAATGGCCGCTGGAACTGCTCTGCACTGGGAGAGCGCACCGTCTTCGGGAAGGAGCTCAAAGTGGGG               AGCCGGGACGGTGCGTTCACCTACGCCATCATTGCCGCCGGCGTGGCCCACGCCATCACAGCTGCCTGTACCCAT               GGCAACCTGAGCGACTGTGGCTGCGACAAAGAGAAGCAAGGCCAGTACCACCGGGACGAGGGCTGGAAGTGGGGT               GGCTGCTCTGCCGACATCCGCTACGGCATCGGCTTCGCCAAGGTCTTCGTGGACGCTCGGGAGATCATGAAGAAC               GCGCGGCGCCTCATGAACCTGCATAACAATGAGGCCGGCAGGAAGGTTCTAGAGGACCGGATGCAGCTGGAGTGC               AAGTGCCACGGCGTGTCTGGCTCCTGCACCACCAAAACCTGCTGGACCACGCTGCCCAAGTTCCGAGAGGTGGGC               CACCTGCTGAAGGAGAAGTACAACGCGGCCGTGCAGGTGGAGGTGGTGCGGGCCAGCCGTCTGCGGCAGCCCACC               TTCCTGCGCATCAAACAGCTGCGCAGCTATCGCAAGCCCATGAAGACGGACCTGGTGTACATCGAGAAGTCGCCC               AACTACTGCGAGGAGGACCCGGTGACCGGCAGTGTGGGCACGCAGGGCCGCGCCTGCAACAAGACGGCTCCCCAG               GCCAGCGGCTGTGACCTCATGTGCTGTGGGCGTGGCTACAACACCCACCAGTACGCCCGCGTGTGGCAGTGCAAC               TGTAAGTTCCACTGGTGCTGCTATGTCAAGTGCAACACGTGCAGCGAGCGCACGGAGATGTACACGTGCAAG TGA                   GCCCCGTGTGCACACCACCCTCCCGCTGCAAGTCAGATTGCTGGGAGGACTGGACCGTTTCCAAGCTGCGGGCTC                   CCTGGCAGGATGCTGAGCTTGTCTTTTCTGCTGAGGAGGGTACTTTTCCTGGGTTTCCTGCAGGCATCCGTGGGG                   GAAAAAAAATCTCTCAGAGCCCTCAACTATTCTGTTCCACACCCAATGCTGCTCCACCCTCCCCCAGACACAGCC                   CAGGTCCCTCCGCGGCTGGAGCGAAGCCTTCTGCAGCAGGAACTCTGGACCCCTGGGCCTCATCACAGCAATATT                   TAACAATTTATTCTGATAAAAATAATATTAATTTATTTAATTAAAAAGAATTCTTCCACCTCGTCGGGATCCGTT                   TTCTGCAATCAAAGTGGACTGCTTGCTTTCCTAGCAGGATGATTTTGTTGCTAGGACAAGGAGCCGTGTAGAAGT                   GTACATAACTATTCTTTATGCAGATATTTCTACTAGCTGATTTTGCAGGTACCCACCTTGCAGCACTAGATGTTT                   AAGTACAAGAGGAGACATCTTTTATGCATATATAGATATACACACACGAAAAA                    
 
       [0168] The sequence of NOV5a was derived by laboratory cloning of cDNA fragments covering the full length and/or part of the DNA sequence of the invention, and/or by in silico prediction of the full length and/or part of the DNA sequence of the invention from public human sequence databases.  
       [0169] The DNA sequence and protein sequence for a novel Wnt-7a-like gene were obtained by SeqCallingTM Technology and are reported here as NOV5a. These methods used to amplify NOV5a cDNA are described in Example 2.  
       [0170] The NOV5a polypeptide (SEQ ID NO: 16) encoded by SEQ ID NO: 15 is 349 amino acid residues in length and is presented using the one-letter amino acid code in Table 5B. The SignalP, Psort and/or Hydropathy results predict that NOV5a has a signal peptide and is likely to be localized extracellularly with a certainty of 0.8200. In alternative embodiments, a NOV5a polypeptide is located to the lysosome (lumen) with a certainty of 0.1900, the endoplasmic reticulum (membrane) with a certainty of 0.1000, or the endoplasmic reticulum (lumen) with a certainty of 0.1000.  
               TABLE 5B                       Encoded NOV5a Protein Sequence                                        (SEQ ID NO:16)                         MNRKARRCLGHLFLSLGMVCLLACGFSSVVALGATVICNKIPGLAPRQTAICQSRPDAIIVIGEGSQMGLDECQ                   FQFRNGRWNCSALGERTVFGKELKVGSRDGAFTYAIIAAGVAHAITAACTHGNLSDCGCDKEKQGQYHRDEGWK               WGGCSADIRYGIGFAKVFVDAREIMKNARRLMNLHNNEAGRKVLEDRMQLECKCHGVSGSCTTKTCWTTLPKFR               EVGHLLKEKYNAAVQVEVVRASRLRQPTFLRIKQLRSYRKPMKTDLVYIEKSPNYCEEDPVTGSVGTQGRACNK               TAPQSGCDLMCCRGYNTHQYARVXQCNCKFHWCCYVKCNTCSERTEMYTCK                  
 
       [0171] NOV5b  
       [0172] In alternative embodiments, a NOV5 variant is NOV5b (alternatively referred to herein as 169475673), which includes a 966 nucleotide sequence (SEQ ID NO: 17) shown in Table 5C below.  
               TABLE 5C                       NOV5b Nucleotide Sequence                                        (SEQ ID NO:17)                         AGATCTCTGGGCGCAACGGTCATCTGTAACAAGATCCCAGGCCTGGCTCCCAGACAGCGAACGATCTGCCAGAG                   CCGGCCCGACGCCATCATCGTCATAGGAGAAAGGCTCACAATCGGCCTGGACGAGTGTCAGTTTCAGTTCCGCA               ATGGCCGCTGGAACTGCTCTGCACTGGGAGAGCGCACCGTCTTCGGGAAGGAGCTCAAAGTGGGGAGCCGGGAG               GCTGCGTTCACCTACGCCATCATTGCCGCCGGCGTGGCCCACGCCATCACAGCTGCCTGTACCCAGGGCAACCT               GAGCGACTGTGGCTGCGACAAAGAGAAGCAAGGCCAGTACCACCGGGACGAGAACTGGAAGTGGGGTGGCTGCT               CTGCCGACATCCGCTACGGCATCGGCTTCGCCAAGGTCTTTGTGGATGCCCGGGAGATCAAGCAGAATGCCCGG               ACTCTCATGAACTTGCACAACAACGAGGCAGGCCGAAAGATCCTGGAGGAGAACATGAAGCTGGAATGTAAGTG               CCACGGCGTGTCAGGCTCGTGCACCACCAAGACGTGCTGGACAACACTGCCAAAGTTTCGGGAGCTGGGCTACG               TGCTCAAGGACAAGTACAACGAGGCCGTTCACGTGGAGCCTGTGCGTGCCAGCCGCAACAAGCGGCCCACCTTC               CTGAAGATCAAGAAGCCACTGTCGTACCGCAAGCCCATGGACACGGACCTGGTGTACATCGAGAAGTCGCCCAA               CTACTGCGAGGAGGACCCGGTGACCGGCAGTGTGGGCACCCAGGGCCGCGCCTGCAACAAGACGGCTCCCCAGG               CCAGCGGCTGTGACCTCATGTGCTGTGGGCGTGGCTACAACACCCACCAGTACGCCCGCGTGTGGCAGTGCAAC               TGTAAGTTCCACTGGTGCTGCTATGTCAAGTGCAACACGTGCAGCGAGCGCACGGAGATGTACACGTGCAAGCT               CGAG                  
 
       [0173] NOV5b is an insert assembly whose sequence was derived by laboratory cloning of cDNA fragments coding for a domain of the full length form of NOV5a (CG50353-01), between residues 32 to 349. The cDNA coding for the NOV5b sequence was cloned by the polymerase chain reaction (PCR). The PCR template is the previoisly identified plasma (NOV5a) when available or human cDNA. These primers and methods used to amplify NOV5b cDNA are described in Example 2.  
       [0174] The NOV5b polypeptide (SEQ ID NO: 18) encoded by SEQ ID NO: 17 is 322 amino acid residues in length and is presented using the one-letter amino acid code in Table 5D.  
               TABLE 5D                       Encoded NOV5b Protein Sequence                                        (SEQ ID NO:18)                         RSLGATVICNKIPGLAPRQRAICQSRPDAIIVIGEGSQMGLDECQFQFRNGRWNCSALGERTCFGKELKCGSREA                   AFTYAIIAAGCAHAITAACTQGNLSDCGCDEKEKQGQYHRDEGWKWGGCSADIRYGIGFAKVFDAREIKQNARTL               MNLHNNEAGRKILEENMKLECKCHGVSGSCTTKTCWTTLPQFRELGYVLKDKYNEAVHVEPVRASRNKRPTFLKI               KKPLSYRKPMDTDLVYIEKSPNYCEEDPVTGSVGTQGRACNKTAPQASGCDIMCCGEGYNTHOYARVWQCNCKFH               WCCYVKCNTCSERTEMYTCKLE                  
 
       [0175] SNP variants of NOV5 are disclosed in Example 3.  
       [0176] NOV5 Clones  
       [0177] Unless specifically addressed as NOV5a or NOV5b, any reference to NOV5 is assumed to encompass all variants.  
       [0178] The amino acid sequence of NOV5 has high homology to other proteins as shown in Table 5E.  
               TABLE 5E                          BLASTX Results from Patp Database for NOV5                                 Smallest           High   Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P (N)                                     patp: AAB19789   Human Wnt-7a protein involved in kidney tubulogenesis   1784   1.1e−183       patp: AAY70737   Human Wnt-7a protein   1784   1.1e−183       patp: AAY57598   Human Wnt-7a protein   1784   1.1e−183       patp: AAY93965   Amino acid sequence of a human WNT-7A polypeptide   1758   6.1e−181       patp: AAR75881   Human Wnt-x    887   1.2e−88                   
 
       [0179] In a search of sequence databases, it was found, for example, that the NOV5a nucleic acid sequence has 1336 of 1412 bases (94%) identical to a gb:GENBANK-ID:HSU53476|acc:U53476.1 mRNA from  Homo sapiens  (Human proto-oncogene Wnt7a mRNA, complete cds). Further, the full amino acid sequence of the disclosed NOV5a protein of the invention has 321 of 349 amino acid residues (91%) identical to, and 335 of 349 amino acid residues (95%) similar to, the 349 amino acid residue ptnr:SWISSPROT-ACC:O00755 protein from  Homo sapiens  (Human) (WNT-7A PROTEIN PRECURSOR).  
       [0180] Additional BLASTP results are shown in Table 5F.  
               TABLE 5F                          NOV5 BLASTP Results                                     Gene Index/       Length of           Expect       Identifier   Protein/Organism   aa   Identity (%)   Positives (%)   Value               O00755   WNT-7A protein precursor -   349   321/349   335/349   1.4e−183             Homo sapiens  (Human)       (91%)   (95%)       AAH08811   UNKNOWN (PROTEIN   349   317/349   333/349   7.8e−181           FOR MGC: 10346) -       (90%)   (95%)             Homo sapiens             (Human)       Q9DBY3   WINGLESS-RELATED   349   315/349   332/349   8.9e−180           MMTV INTEGRATION       (90%)   (95%)           SITE 7A -             Mus musculus  (Mouse)       P24383   WNT-7A protein   349   313/349   330/349   3.5e−178           precursor -       (89%)   (94%)             Mus musculus  (Mouse)       Q9DEB8   WNT-7A -  Gallus gallus     349   302/349   329/349   4.7e−174           (Chicken)       (86%)   (94%)                  
 
       [0181] A multiple sequence alignment is given in Table 5G in a ClustalW analysis comparing NOV5 with related protein sequences disclosed in Table 5F. 
 
 
 
       [0182] Domain results for NOV5 were collected from BLAST sample domains found in the Smart and Pfam collections, and then identified by the Interpro domain accession number. The results are listed in Table 5H with the statistics and domain description. These results indicate that the NOV5 polypeptides have properties similar to those of other proteins known to contain these domains and similar to the properties of these domains.  
               TABLE 5H                       Domain Analysis of NOV5                                                    Score   E           PSSMs Producing Significant Alignments   (bits)   Value               writ: domain 1 of 1, from 37 to 349   716.5   3e−260                                     Wnt   lCrslPGLsprQrqlcrrnpdvmasvseGaqlaiqEcQhQFRgrRWN   (SEQ ID NO:71)               +|+++|||+++|+++|++++++++++++|++++ +|||+|||++|||       NOV5a   ICNKIPGLAPRQRAICQSRPDAIIVIGEGSQMGLDECQFQFRNGRWN   (SEQ ID NO:16)                   CStldslnersvfgkvlkkgtREtAFvyAIsSAGVahaVTRaCseGeles           ||+++   +++++++++++++|++||++|| +|||++++|++|  |++++       NOVSa   CSALG---ERTVFGKELKVGSRDGAFTYAIIAAGVAHAITAACTHGNLSD                   CGCDdkRkadeerlrikLepkgpggpqgswkwGGcsDNvefGirfSReFV           ||||+             +++++++ +++ +     +++++ +++++ ||       NOV5a   CGCDK-------------EKQGQYHRDEGWKWGGCSADIRYGIGFAKVFV                   DarEreklmtksrdrdaRsLMNLHNNEAGRkaVkshmrreCKCHGvSGSC            ++ +       ++  +|+|||||||||||+++++++ ++|||||+||||       NOV5a   DAREIM------KN--ARRLMNLHNNEAGRKVLEDRMQLECKCHGVSGSC                   slKTCWlsLPdFReVGdlLKeKYdgAievevnkrgkgqrslssrkqasal           ++||||++||+||+||++||+||+ |++|+++++++       +++++++       NOVSa   TTKTCWTTLPKFREVGHLLKEKYNAAVQVEVVPASR------LRQPTFLR                   eaanerfkkptrnQYTDLvylEkSPDYCerdretQslGTqcRvcnktskG           +++ +++++|+++   ||||+|+||+||++++ +|++||+||+|++++++       NOV5a   IKQLRSYRKPMKT---DLVYIEKSPNYCEEDPVTGSVGTQGRACNKTAPQ                   lqWRDgCelLCCGRGYnteqKvertekCnCkFHNGWCCyVkCeeCtevve           +   ++|+++||||||++++ + ++++|+|+||++|||+|+|++|+++++       NOV5a   A---SGCDLMCCGRGYNTHQ-YARVWQCNCKFH--WCCYVKCNTCSERTE                   vhtCK           +++||       NOV5a   MYTCK                  
 
       [0183] The Wnt-7a-like protein disclosed in this invention is expressed in at least the following tissues: testis, pancreas, brain, coronary artery, dermis, prostate, uterus and ovary. This information was derived by determining the tissue sources of the sequences that were included in the invention, including but not limited to, SeqCalling sources, PublicEST sources, RACE sources, and publicly available reference material from OMIM and Pubmed.  
       [0184] The protein similarity information, expression pattern, and map location for the Wnt-7a-like protein and nucleic acid disclosed herein suggest that this protein may have important structural and/or physiological functions characteristic of the Wnt family. Therefore, the NOV5 nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, the compositions of the present invention will have efficacy for treatment of patients suffering from: atherosclerosis, aneurysm, hypertension, fibromuscular dysplasia, stroke, scleroderma, obesity, transplantation disorders, myocardial infarction, embolism, cardiovascular disorders, bypass surgery, endometriosis, infertility, polycystic ovary syndrome, Von Hippel-Lindau (VHL) syndrome, Alzheimer&#39;s disease, tuberous sclerosis, hypercalceimia, Parkinson&#39;s disease, Huntington&#39;s disease, cerebral palsy, epilepsy, Lesch-Nyhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, neurodegeneration, cancer, psoriasis, actinic keratosis, acne, hair growth/loss, allopecia, pigmentation disorders, endocrine disorders, pancreatitis, diabetes and other diseases, disorders and conditions of the like.  
       [0185] The novel nucleic acid encoding the Wnt-7a-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV5 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV5 epitope is from about amino acids 40 to 50. In another embodiment, a contemplated NOV5 epitope is from about amino acids 52 to 57. In other specific embodiments, contemplated NOV5 epitopes are from about amino acids 57 to 60, 65 to 100, 125 to 150, 165 to 210, 210 to 230, 230 to 240, 240 to 295, 300 to 325, and 325 to 340.  
       [0186] NOV6  
       [0187] Another NOVX protein of the invention, referred to herein as NOV6, includes two novel apical endosomal glycoprotein (AEG)-like proteins. The disclosed proteins have been named NOV6a and NOV6b.  
       [0188] After endocytosis from the plasma membrane, internalized receptors and ligands are delivered to endosomes. The endosomal compartment performs a variety of functions, including the sorting of internalized receptors and ligands, and newly synthesized lysosomal membrane proteins and hydrolases. In polarized epithelial cells, the apical endosomal compartment plays a role in both apical to basolateral and basolateral to apical transepithelial transport.  
       [0189] The NOV6 proteins disclosed here are predicted to localize at the plasma membrane. Therefore, it is likely that these proteins are accessible to a diagnostic probe, and for the various therapeutic applications described herein.  
       [0190] At least the NOV6a protein of the invention maps to chromosome 9. This information was assigned using OMIM, the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0191] NOV6a  
       [0192] In one embodiment, a NOV6 variant is NOV6a (alternatively referred to herein as CG50221-01), which encodes a novel apical endosomal glycoprotein (AEG)-like protein and includes the 3731 nucleotide sequence (SEQ ID NO: 19) shown in Table 6A. An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 39-41 and ending with a TAG codon at nucleotides 3699-3701. Putative untranslated regions downstream from the termination codon and upstream from the initiation codon are underlined in Table 6A, and the start and stop codons are in bold letters. Table 6A. NOV6a Nucleotide Sequence (SEQ ID NO: 19)  
               TABLE 6A                       NOV6a Nucleotide Sequence                                        (SEQ ID NO:19)                           GCACCCTGTGTGGCCGCACTGCTCCCTCTGGCCCAACC   ATG CCTCTGTCCAGCCACCTGCTGCCCGCCTTGGTCCT                   GTTCCTGGCAGCAGGGTCCTCAGGCTGGGCCTGGGTCCCCAACCACTGCAGGAGCCCTGGCCAGGCCGTGTGCAAC               TTCGTGTGTGACTGCAGGGACTGCTCAGATGAGGCCCAGTGTGGTTACCACGGGGCCTCGCCCACCCTGGGCGCCC               CCTTCGCCTGTGACTTCGAGCAGGACCCCTGCGGCTGGCGGGACATTAGTACCTCAGGCTACAGCTGGCTCCGAGA               CAGGGCAGGGGCCGCACTGGAGGGTCCTGGGCCTCACTCAGACCACACACTGGGCACCGACTTGGGCTGGTACATG               GCCGTTGGAACCCACCGAGGGAAAGACGCATCCACCGCAGCCCTGCGCTCGCCAACCCTGCGAGAGGCAGCCTCCT               CTTGCAAGCTGAGGCTCTGGTACCACGCGGCCTCTGGAGATGTGGCTGAACTGCGGGTGGAGCTGACCCATGGCGC               AGAGACCCTGACCCTGTGGCAGAGCACAGGGCCCTGGGGCCCTGGCTGGCAGGAGTTGGCAGTGACCACAGGCCGC               ATCCGGGGTGACTTCCGAGTGACCTTCTCTGCCACCCGAAATGCCACCCACAGGGGCGCTGTAACTCTAGATGACC               TAGAGTTCTGGGACTGTGGTCTGCCCACCCCCCAGGCCAACTGTCCCCCGGGACACCACCACTGCCAGAACAAGGT               CTGCGTGGAGCCCCAGCAGCTGTGCGACGGGGAAGACAACTGCGGGGACCTGTCTGATGAGAACCCACTCACCTGT               GGCCGCCACATAGCCACCGACTTTGAGACAGGCCTGGGCCCATGGAACCGCTCGGAAGGCTGGTCCCGGAACCACC               GCGCTGGTGGTCCTGAGCGCCCCTCCTGGCAACGCCGTGACCACAGCCGGAACAGTGCACAGGGCTCCTTCCTGGT               CTCCGTGGCCGAGCCTGGAACCCCTGCTATACTCTCCAGCCCCGAATTCCAAGCCTCAGGCACCTCCAACTGCTCG               GTGAGATGGCTGGTCTTCTATCAGTACCTGAGTGGGTCTGAGGCTGGCTGCCTCCAGCTGTTCCTGCAGACTCTGG               GGCCCGGCGCCCCCCGGGCCCCCGTCCTGCTGCGGAGGCGCCGAGGGGAGCTGGGGACCGCCTGGGTCCGAGACCG               TGTTGACATCCAGAGCGCCTACCCCTTCCAGATCCTCCTGGCCGGGCAGACAGGCCCGGGGGGCGTCGTGGGTCTG               GACGACCTCATCCTGTCTGACCACTGCAGACCAGTCTCGGAGGTGTCCACCCTGCAGCCGCTGCCTCCTGGGCCCC               GGGCCCCAGCCCCCCAGCCCCTGCCGCCCAGCTCGCGGCTCAAGGATTCCTGCAAGCAGGGGCATCTTGCCTGCGG               GGACCTGTGTGTGCCCCCGGAACAACTGTGTGACTTCGAGGAGCAGTGCGCAGGGGGCGAGGACGAGCAGGCCTGT               GGCACCACAGACTTTGAGTCCCCCGAGGCTGGGGGCTGGGAGGACGCCAGCGTGGGGCGGCTGCAGTGGCGGCGTG               TCTCAGCCCAGGAGAGCCAGGGGTCCAGTGCAGCTGCTGCTGGGCACTTCCTGTCTCTGCAGCGGGCCTGGGGGCA               GCTAGGCGCTGAGGCCCGGGTCCTCACACCCCTCCTTGGCCCTTCTGGCCCCAGCTGTGAACTCCACCTGGCTTAT               TATTTACAGAGCCAGCCCCGAGGCTTCCTGGCACTAGTTGTGGTGGACAACGGCTCCCGGGAGCTGGCATGGCAGG               CCCTGAGCAGCAGTGCAGGCATCTGGAAGGTGGACAAGGTCCTTCTAGGGGCCCGCCGCCGGCCCTTCCGGCTGGA               GTTTGTCGGTTTGGTGGACTTGGATGGCCCTGACCAGCAGGGAGCTGGGGTGGACAACGTGACCCTGAGGGACTGT               AGCCCCACAGTGACCACCGAGAGAGACAGAGAGGTCTCCTGTAACTTTGAGCGGGACACATGCAGCTGGTACCCAG               GCCACCTCTCAGACACACACTGGCGCTGGGTGGAGAGCCGCGGCCCTGACCACGACCACACCACAGGCCAAGGCCA               CTTTGTGCTCCTGGACCCCACAGACCCCCTGGCCTGGGGCCACAGTGCCCACCTGCTCTCCAGGCCCCAGGTGCCA               GCAGCACCCACGGAQTGTCTCAGCTTCTGGTACCACCTCCATGGGCCCCAGATTGGGACTCTGCGCCTAGCCATGA               GACGGGAAGGGGAGGAGACACACCTGTGGTCGCGGTCAGGCACCCAGGGCAACCGCTGGCACGAGGCCTGGGCCAC               CCTTTCCCACCAGCCTGGCTCCCATGCCCAGTACCAGCTGCTGTTCGAGGGCCTCCGGGACGGATACCACGGCACC               ATGGCGCTGGACGATGTGGCCGTGCGGCCGGGCCCCTGCTGGGCCCCTAATTACTGCTCCTTTGAGGACTCAGACT               GCGGCTTCTCCCCTGGAGGCCAAGGTCTCTGGAGGCGGCAGGCCAATGCCTCGGGCCATGCTGCCTGGGGCCCCCC               AACAGACCATACCACTGAGACAGCCCAAGGGCACTACATGGTGGTGGACACAAGCCCAGACGCACTACCCCGGGGC               CAGACGGCCTCCCTGACCTCCAAGGAGCACAGGCCCCTGGCCCAGCCTGCTTGTCTGACCTTCTGGTACCACGGGA               GCCTCCGCAGCCCAGGCACCCTGCGGGTCTACCTGGAGGAGCGCGGGAGGCACCAGGTGCTCAGCCTCAGTGCCCA               CGGCGGGCTTGCCTGGCGCCTGGGCAGCATGGACGTGCAGGCCGAGCGAGCCTGGAGGGTGGTGTTTGAGGCAGTG               GCCGCAGGCGTGGCACACTCCTACGTGGCTCTGGATGATCTGCTCCTCCAGGACGGGCCCTGCCCTCAGCCAGGTT               CCTGTCATTTTGAGTCTGGCCTGTGTGGCTGGAGCCACCTGGCCTGGCCCGGCCTGGGCGGATACAGCTGGGACTG               GGGCGGGGGAGCCACCCCCTCTCGTTACCCCCAGCCCCCTGTGGACCACACCCTGGGCACAGAGGCAGGCCACTTT               GCCTTCTTTGAAACTGGCGTGCTGGGCCCCGGGGGCCGGGCCGCCTGGCTGCGCAGCGAGCCTCTGCCGGCCACCC               CAGCCTCCTGCCTCCGCTTCTGGTACCACATGGGTTTTCCTGAGCACTTCTACAAGGGGGAGCTGAAGGTACTGCT               GCACAGTGCTCAGGGCCAGCTGGCTGTGTGGGGCGCAGGCGGGCATCGGCGGCACCAGTGGCTGGAGGCCCAGGTG               GAGGTAGCCAGTGCCAAGGAGTTCCAGATCGTGTTTGAAGCCACTCTGGGCGGCCAGCCAGCCCTGGGGCCCATTG               CCCTGGATGACGTGGAGTATCTGGCTGGGCAGCATTGCCAGCAGCCTGCCCCCAGCCCGGGGAACACAGCCGCACC               CGGGTCTGTGCCAGCTGTGGTTGGCAGTGCCCTCCTATTGCTCATGCTCCTGGTGCTGCTGGGACTTGGGGGACGG               CGCTGGCTGCAGAAGAAGGGGAGCTGCCCCTTCCAGAGCAACACAGAGGCCACAGCCCCTGGCTTTGACAACATCC               TTTTCAATGCGGATGGTGTCACCCTCCCGGCATCTGTCACCAGTGATCCG TAG   ACCACCCCAGACAAGGCCC                   CGCTTCCTCAC                    
 
       [0193] The sequence of NOV6a was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0194] The NOV6a polypeptide (SEQ ID NO: 20) encoded by SEQ ID NO: 19 is 1220 amino acid residues in length and is presented using the one-letter amino acid code in Table 6B. The SignalP, Psort and/or Hydropathy results predict that NOV6a has a signal peptide and is likely to be localized extracellularly at the plasma membrane with a certainty of 0.4600. In alternative embodiments, a NOV6a polypeptide is located to the microbody (peroxisome) with a certainty of 0.2742, the endoplasmic reticulum (membrane) with a certainty of 0.1000, or the endoplasmic reticulum (lumen) with a certainty of 0.1000. The SignalP predicts a likely cleavage site for a NOV6a peptide between amino acid positions 23 and 24, i.e. at the dash in the sequence GWA-WV.  
               TABLE 6B                       Encoded NOV6a Protein Sequence                                        (SEQ ID NO:20)                         MPLSSHLLPALVLFLAAGSSGWANVPNHCRSPGGAVCNFVCDCRDCSDEAQCGYHGASPTLGAPFACDFEQDPC                   GWRDISTSGYSWLRDRAGAALEGPGPHSDHTLGTDLGWYMAVGTHRGKEASTAALRSPTLREAASSCKLRLWYH               AASGDVAELRVELTHGAETLTLWQSTGPWGPGWQELAVTTGRIRGDFRVTFSATRNATHRGAVALDDLEFWDCG               LPTPQANCPPGHHHCQNKVCVEPQQLCDGEDNCGDLSDENPLTCGRHIATDFETGLGPWNRSEGWSRNHRAGGP               ERPSWPRRDHSRNSAQGSFLVSVAEPGTPAILSSPEFQASGTSNCSVRWLVFYQYLSGSEAGCLQLFLQTLGPG               APRAPVLLRRRRGELGTAWVRDRVDIQSAYPFQILLAGQTGPGGVVGLDDLILSDHCRPVSEVSTLQPLPPGPR               APAPQPLPPSSRLQDSCKQGHLACGDLCVPPEQLCDFEEQCAGGEDEQACGTTDFESPEAGGWEDASVGRLQWR               RVSAQESQGSSAAAAGHFLSLQRAWGQLGAEARVLTPLLGPSGPSCELHALYYLQSQPRGFLALVVVDNGSREL               AWQALSSSAGIWKVDKVLLGARRRPFRLEFVGLVDLDGPDQQGAGVDNTLRDCSPAAJTTERDREVSCNFERDT               CSWYPGHLSDTHWRWVESRGPDHDHTTGQGHFVLLDPTDPLAWGHSAHLLSRPQVPAAPTECLSFWYHAAGPQI               GTLRLAMRREGEETHLWSRSGTQGNRWHEAWATLSHQPGSHAQYQLLFEGLRDGYHGTMALKKVAVRPGPCWAP               NYCSFEDSDCGFSPGGGGLWRRQANASGHAAWGPPTDHTTETAQGHYIVAATSPDAAPRGGTASLTSKEHRPAA               QPACLTFWYHGSLRSPGTLRVYLEERGRHQVLSLSAHGGLAWRLGSMDVQAERAWRVVFEAVAAGVAHSYVALD               DLLLQDGPCPQPGSCDFESGLCGWSHAAWPGLGGYSAAWGGGATPSRYPQPPAAHTLGTAAGHFAFFETGVLGP               GGRAAWLRSEPLPATPASCLRFWYAAGFPEHFYKGELAALLESAQGQLAVWGAGGHRRHQWLEAQVEVASAKEF               QIVFEATLGGQPALGPIALDDVEYLAGGHCGGPAPSPGAATAAPGSVPAWGSALLLLMLLVLLGLGGRRWLQKK               GSCPFQSNTEATAPGFDNTLFNADQVTLPASVTSDP                  
 
       [0195] NOV6b  
       [0196] In an alternative embodiment, a NOV6 variant is NOV6b (alternatively referred to herein as 174308633), which includes 1857 nucleotides. NOV6b is an insert assembly that was found to encode an open reading frame between residues 31 and 648 of the target sequence of NOV6a. NOV6b differs from NOV6a at 4 nucleotide and 4 amino acid positions. It also contains a 3 amino acid deletion, and a 9 nucleotide deletion in comparison with NOV6a. Table 6C notes the changes in nucleotide and amino acid sequences from the parent clone, NOV6a.  
                           TABLE 6C                                   Change in       Nov   Alternate   Change in DNA Seq.   Protein Seq. from       No.   Reference   from NOV6a   NOV6a                  6b   174308633   T → C at bp 385;   V → A at aa 116;               C → T at bp 914;   A → T at aa 326;               C → T at bp 1007; and   T → L at aa 649; and               G → A at bp 1014   V → E at aa 650                  
 
       [0197] The sequence of NOV6b was derived by laboratory cloning of cDNA fragments coding for a domain of the full length form of NOV6a, between residues 31 and 648. The cDNA coding for the NOV6b sequence was cloned by the polymerase chain reaction (PCR). The PCR template is the previoisly identified plasma (NOV6a) when available or human cDNA. These primers and methods used to amplify NOV6b cDNA are described in Example 2.  
       [0198] SNP variants of NOV6 are disclosed in Example 3.  
       [0199] NOV6 Clones  
       [0200] Unless specifically addressed as NOV6a or NOV6b, any reference to NOV6 is assumed to encompass all variants.  
       [0201] The amino acid sequence of NOV6 has high homolgy to other proteins as shown in Table 6D.  
               TABLE 6D                          BLASTX Results from Patp Database for NOV6                                 Smallest           High   Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P (N)                                     patp: AAB42780   Human ORFX ORF2544 polypeptide   1274     2.5e−230       patp: AAB01432   Human TANGO 239 (form 2)   377   2.4e−33       patp: AAB00036   Human TANGO 239 partial sequence   281   4.9e−21       patp: AAB01426   Human TANGO 239   271   2.5e−19       patp: AAE00585   Human nuclear cell adhesion molecule homologue   225   2.3e−14                  
 
       [0202] In a search of sequence databases, it was found, for example, that the NOV6a nucleic acid sequence of this invention has 913 of 945 bases (96%) identical to a gb:GENBANK-ID:HSM801957|acc:AL137659.1 mRNA from  Homo sapiens  ( Homo sapiens  mRNA; cDNA DKFZp434I1716 (from clone DKFZp434I1716)). Further, the full amino acid sequence of the disclosed protein of the invention has 885 of 1220 amino acid residues (72%) identical to, and 990 of 1220 amino acid residues (81%) similar to, the 1216 amino acid residue ptnr:SWISSPROT-ACC:Q63191 protein from  Rattus norvegicus  (Rat) (APICAL ENDOSOMAL GLYCOPROTEIN PRECURSOR).  
       [0203] Additional BLASTP results are shown in Table 6E.  
               TABLE 6E                          NOV6 BLASTP Results                                     Gene Index/       Length of           Expect       Identifier   Protein/Organism   aa   Identity (%)   Positives (%)   Value                                             Q63191   Apical endosomal   1216   885/1220   990/1220   0.0           glycoprotein precursor -       (72%)   (81%)             Rattus norvegicus  (Rat)       Q91641   Thyroid hormone-induced   668   131/452   212/452   1.4e−31           protein B precursor -       (28%)   (46%)             Xenopus laevis  (African           clawed frog)       O88799   Zonadhesin precursor -   5376   146/502   228/502   9.8e−28             Mus musculus  (Mouse)       (29%)   (45%)       Q99ND0   ZAN -  Mus musculus     5374   146/502   227/502   1.3e−27           (Mouse)       (29%)   (45%)       Q9BZ84   ZONADHESIN VARIANT   2601   149/491   215/491   5.4e−23           5 -  Homo sapiens  (Human)       (30%)   (43%)                  
 
       [0204] A multiple sequence alignment is given in Table 6F, with the NOV6 protein of the invention being shown in lines 1 and 2, in a ClustalW analysis comparing NOV6 with related protien sequences of Table 6E. 
 
 
 
 
 
 
 
 
 
 
 
 
 
       [0205] Domain results for NOV6 were collected from the Pfam database, and then identified by the Interpro domain accession number. The results are listed in Table 6G with the statistics and domain description. These results indicate that the NOV6 polypeptides have properties similar to those of other proteins known to contain these domains.  
               TABLE 6G                       Domain Analysis of NOV6                                                    Score   E           PSSMs Producing Significant Alignments   (bits)   Value               MAM: domain 4 of 6, from 660 to 813   192.5   6.7e−54                                     MAM   CdFEdgshFfCgWsqdsgddgddlqwtrvnsatggstgprgdhttGn   (SEQ ID NO:77)               |+|| +    | |  +++++    +| ++ ++     ++ +++++|+       NOVGa   CNFERDT---CSWYPGHLSD---THWRVESR-----GPDHDHTTGQ   (SEQ ID NO:20)                   GhymyvdtssgllqeGqkArLlSpplppnrspeccLtFwYhmyGsgvgtp           |++ ++++++ + + |++|+|+|++  ++++   ||+|+|+++|++ ++       NOV6a   GHFVLLDPTDPL-AWGHSAHLLSRPQVPAAPT-ECLSFWYHLHGPQIGT-                   gLnvyvrenge.tllWsrsGhqggqWllaevtlpt..fstkptqvvFegt            |+++++++++++ +|+++|++++++|++++ ++++++++ +++++|+++       NOV6a   -LRLAMRREGEeTHLWSRSGTQGNRWHEAWATLSHqpGSHAQYQLLFEGL                   rgggsrGgIAlDDIslsthiegpcnq           +  +++|++|+||+ ++   +++|++       NOV6a   R-DGYHGTMALDDVAVR---PGPCWA                                 MAM: domain 6 of 6, from 977 to 1142   199.2   6.4e−56                                     MAM   CdFEdgshPfCgWsqdsgddgddlqWtrvnsatgg.stgprgdhttG   (SEQ ID NO:78)               |+||++   +|+|++  +++++++ | ++ ++++++++ ++++++ |           CDFESG---LCGWSHLAWPGLGGYSWDWGGGATPSrYPQPPVDHTLG   (SEQ ID NO:20)                   n..GhymyvdtssgllqeGqkArLlspplppnrspeccLtFwyhmyGsgv           ++ |++ ++++ + + ++|++|+|+|++++++  +  ||+|+|++ ++++       NOV6a   TeaGHFAFFETGVLG-PGGRAAWLRSEPLPATPAS--CLRFWYHMGFPEH                   gtpg.Lnvyvrenge.tllWsrsGhqggqwllaevtlptfstkpfqvvFe            ++++| +++ + +++  +| ++|+  ++|+++++++   + ++++++|+       NOV6a   FYKGeLKVLLHSAQGqLAVWGAGGHRPHQWLEAQVEVA--SAKEFQIVFE                   gtrg.ggsrGgIAlDDlslsthiegpcnq           ++ ++++ +| ||+||+++++  +++| +       NOV6a   ATLGgQPALGPIALDDvEyLA-GGHcQQ                  
 
       [0206] The NOV6 disclosed in this invention may be expressed in a variety of tissues.  
       [0207] The protein similarity information, expression pattern, and map location for the apical endosomal glycoprotein-like protein and nucleic acid disclosed herein suggest that this protein may have important structural and/or physiological functions characteristic of the apical endosomal glycoprotein family. Therefore, the nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, the compositions of the present invention will have efficacy for treatment of patients suffering from: endometriosis, fertility and other diseases, disorders and conditions of the like.  
       [0208] The novel nucleic acid encoding the apical endosomal glycoprotein-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV6 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV6 epitope is from about amino acids 20 to 150. In another embodiment, a contemplated NOV6 epitope is from about amino acids 150 to 200. In alternative embodiments, contemplated NOV6 epitopes include from about amino acids 205 to 310, 320 to 355, 375 to 410, 410 to 440, 440 to 550, 570 to 740, 740 to 800, 800 to 950, 950 to 990, 995 to 1025, 1045 to 10 1070, 1100to 1120, 1125 to 1160, and 1175 to 1210.  
       [0209] NOV7  
       [0210] Another NOVX protein of the invention, referred to herein as NOV7, includes three novel ADAM13-like proteins. The disclosed proteins have been named NOV7a, NOV7b, and NOV7c. The ADAM family proteins contain a metalloprotease domain, a disintegrin domain, and a cystein-rich domain. The proteins are human homolgs of mouse meltrin-alpha, which are involved in mytube formation  
       [0211] The NOV7 proteins disclosed herein are predicted to localize extracellularly. Therefore, it is likely that these proteins are accessible to a diagnostic probe, and for the various therapeutic applications described herein.  
       [0212] At least the NOV7a protein disclosed in this invention maps to chromosome 20. This information was assigned using OMIM, the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0213] NOV7a  
       [0214] In one embodiment, a NOV7 variant is NOV7a (alternatively referred to herein as CG50367-01), which encodes a novel ADAM13-like protein and includes the 2762 nucleotide sequence (SEQ ID NO: 21) shown in Table 7A. An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 3-5 and ending with a TGA codon at nucleotides 2745-2747. Putative untranslated regions downstream from the termination codon and upstream from the initiation codon are underlined in Table 7A, and the start and stop codons are in bold letters.  
               TABLE 7A                       NOV7a NuCleotide Sequence                                        (SEQ ID NO:21)                           CT   ATG GGCTGGAGGCCCCGGAGAGCTCGGGOGACCCCGTTGCTGCTGCTGCTACTACTGCTGCTGCTCTGGCCAG                   TGCCAGGCGCCGGGGTGCTTCAAGGACATATCCCTGGGCAGCCAGTCACCCCGCACTGGGTCCTGGATGGACAAC               CCTGGCGCACCGTCAGCCTGGAGGAGCCGGTCTCGAAGCCAGACATQGGGCTGCTGGCCCTGGAGGCTGAAGGCC               AGGAGCTCCTGCTTGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCAGGATACATAGAAACCCACTACGGCCCAG               ATGGGCAGCCAGTGGTGCTGGCCCCCAACCACACGGATCATTGCCACTACCAAGGGCGAGTAAGGGGCTTCCCCG               ACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGATGAGTGGCCTGATCACCCTCAGCAGGAATGCCAGCTATTATC               TGCGTCCCTGGCCACCCCGGGGCTCCAAGGACTTCTCAACCCACGAGATCTTTCGGATGGAGCAGCTGCTCACCT               GGAAAGGAACCTGTGGCCACAGGGATCCTGGGAACAAAGCGGGCATGACCAGCCTTCCTGGTGGTCCCCAGAGCA               GGGGCAGGCGAGAAGCGCGCAGGACCCGGAAGTACCTGGAACTGTACATTGTGGCAGACCACACCCTGTTCTTGA               CTCGGCACCGAAACTTGAACCACACCAAACAGCGTCTCCTGGAAGTCGCCAACTACGTGGACCAGCTTCTCAGGA               CTCTGGACATTCAGGTGGCGCTGACCGGCCTGGAGGTGTGGACCGAGCGGGACCGCAGCCGCGTCACGCAGGACG               CCAACGCCACGCTCTGGGCCTTCCTGCAGTGGCGCCGGGGGCTGTGGGCGCAGCGGCCCCACGACTCCGCGCAGC               TGCTCACGGGCCGCGCCTTCCAGGGCGCCACAGTGGGCCTGGCGCCCGTCGAGGGCATGTGCCGCGCCGAGAGCT               CGGGAGGCGTGAGCACGGACCACTCGGAGCTCCCCATCGGCGCCGCAGCCACCATGGCCCATGAGATCGGCCACA               GCCTCGGCCTCAGCCACGACCCCGACGGCTGCTGCGTGGAGGCTGCGGCCGAGTCCGGAGGCTGCGTCATGGCTG               CGGCCACCGGGCACCCGTTTCCGCGCGTGTTCAGCGCCTGCAGCCGCCGCCAGCTGCGCGCCTTCTTCCGCAAGG               GGGGCGGCGCTTGCCTCTCCAATGCCCCGGACCCCGGACTCCCGGTGCCGCCGGCGCTCTGCGGGAACGGCTTCG               TGGAAGCGGGCGAGGAGTGTGACTGCGGCCCTGGCCAGGAGTGCCGCGACCTCTGCTGCTTTGCTCACAACTGCT               CGCTGCGCCCGGGGGCCCAGTGCGCCCACGGGGACTGCTGCGTGCGCTGCCTGCTGAAGCCGGCTGGAGCGCTGT               GCCGCCAGGCCATGGGTGACTGTGACCTCCCTGAGTTTTGCACGGGCACCTCCTCCCACTGTCCCCCAGACCTTT               ACCTACTGGACGGCTCACCCTGTGCCAGGGGCAGTGGCTACTGCTGGGATGGCGCATGTCCCACGCTGGAGCAGC               AGTGCCAGCAGCTCTGGGGGCCTGGCTCCCACCCAGCTCCCGAGGCCTGTTTCCAGGTGGTGAACTCTGCGGGAG               ATGCTCATGGAAACTQCGGCCAGGACAGCGAGGGCCACTTCCTGCCCTGTGCAGGGAGGGATGCCCTGTGTGGGA               AGCTGCAGTGCCAGGGTGGAAAGCCCAGCCTGCTCGCACCGCACATGGTGCCAGTGGACTCTACCGTTCACCTAG               ATGGCCAGGAAGTGACTTGTCGGGGAGCCTTGGCACTCCCCAQTGCCCAGCTGGACCTGCTTGGCCTGGGCCTGG               TAGAGCCAGGCACCCAGTGTGGACCTAGAATGGTGTGCCAGAGCAGGCGCTGCAGGAAGAATGCCTTCCAGGAGC               TTCAGCGCTGCCTGACTGCCTGCCACAGCCACGGGGTTTGCAATAGCAACCATAACTGCCACTGTGCTCCAGGCT               GGGCTCCACCCTTCTGTGACAAGCCAGGCTTTGGTGGCAGCATGGACAGTGGCCCTGTGCAGGCTGAAAACCATG               ACACCTTCCTGCTGGCCATGCTCCTCAGCGTCCTGCTGCCTCTGCTCCCAGGGGCCGGCCTGGCCTGGTGTTGCT               ACCGACTCCCAGGAGCCCATCTGCAGCGATGCAGCTGGGGCTGCAGAAGGGACCCTGCGTGCAGTGGCCCCAAAG               ATGGCCCACACAGGGACCACCCCCTGGGCGGCGTTCACCCCATGGAGTTGGGCCCCACAGCCACTGGACAGCCCT               GGCCCCTGGCCCCAGGGGCTCCTGCTGACCATATTCACAACATTTACCCTCCACCATTTCTCCCAGACCCTGAGA               ACTCTCATGAGCCCAGCAGCCACCCTGAGAAGCCTCTGCCAGCAGTCTCGCCTGACCCCCAAGGTGGTTCCCTTG               CAGCCTGGGGCCCCAGTCCTTTAGGGGACAACATATCCTCCTCATTCTCAGCAGATCAAGTCCAGATGCCAAGAT               CCTGCCTCTGTGGCGAACCCTGGGGAGGCCACGTGGGAAGGAAAGAGGGCTCTAAGAGGGGAGGCCCCAGACTGG               GGGAGAGGCCTGTCTGGAGCCCAGGATCACCTGGCTGTGCTGCAGAACTGGAGAAGAGAAGCTCAGCAGAAAGGA               GCTGGCATGGGGCCAACAGCAGAAAAGCAGGAGGCACGCAGAAG TGA   CTGGGAAGCAGGAGG                    
 
       [0215] The sequence of NOV7a was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0216] The DNA sequence and protein sequence for a novel transmembrane-like gene were obtained by SeqCallingTM Technology and are reported here as NOV7a. These methods used to amplify NOV7a cDNA are described in Example 2.  
       [0217] The NOV7a polypeptide (SEQ ID NO: 22) encoded by SEQ ID NO: 21 is 914 amino acid residues in length and is presented using the one-letter amino acid code in Table 7B. The SignalP, Psort and/or Hydropathy results predict that NOV7a has a signal peptide and is likely to be localized extracellularly at the plasma membrane with a certainty of 0.4600. In alternative embodiments, a NOV7a polypeptide is located to the microbody (peroxisome) with a certainty of 0.1026, the endoplasmic reticulum (membrane) with a certainty of 0.1000, or the endoplasmic reticulum (lumen) with a certainty of 0.1000. The SignalP predicts a likely cleavage site for a NOV7a peptide between amino acid positions 29 and 30, i.e. at the dash in the sequence GAG-VL.  
               TABLE 7B                       EnCoded NOV7a Protein Sequence                                        (SEQ ID NO:22)                         MGWRPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPVSKPDMGLVALEAEG                   QELLLELEKNHRLLAPGYIETHYGPDGQPVVLAPNHTDHCHYQGRVRGFPDSWVVLCTCSGMSGLLTLSRNASY               YLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCGHRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTL               FLTRHRNLNHTKQRLLEVANYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATLWAFLQWRRGLWAQRPHD               SAQLLTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGCCVEAAAESGG               CVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALCGNGFVEAGEECDCGPGGECRDLCC               FAHNCSLRPGAQCAHGDCCVRCLLKPAGALCRQAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCARGSGYCWDGA               CPTLEQQCGGLWGPGSHPAPEACFQVVNSAGDAHGNCGGDSEGHFLPCAGRDALCGKLQCGGGKPSLLAPHMVP               VDSTVHLDGQEVTCRGALALPSAQLDLLGLGLVEPGTQCGPRMVCGSRRCRKNAFQELQRCLTACHSHGVCNSN               HNCHCAPGWAPPFCDKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLPLLPGAGLAWCCYRLPGAHLQRCSWGCR               RDPACSGPKDGPHRDHPLGGVHPMELGPTATGGPWPLAPGAPADHIHNIYPPPFLPDPENSHEPSSHPEKPLPA               VSPDPQGGSLAAWGPSPLGDNISSSFSADQVQMPRSCLCGEPWGGHVGRKEGSKRGGPRLGERPVWSPGSPGCA               AELEKRSSAERSWHGANSRKAGGTQK                  
 
       [0218] NOV7b  
       [0219] In an alternative embodiment, a NOV7 variant is NOV7b (alternatively referred to herein as CG50367-02), which includes the 2705 nucleotide sequence (SEQ ID NO: 23) shown in Table 7C. An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 3-5 and ending with a TGA codon at nucleotides 2688-2690. The start and stop codons of the open reading frame are highlighted in bold type. Putative untranslated regions are underlined and found upstream from the initiation codon and downstream from the termination codon.  
               TABLE 7C                       NOV7b NuCleotide Sequence                                        (SEQ ID NO:23)                           CT   ATG GGCTGGAGGCCCCGGAGAGCTCGGGGGACCCCGTTGCTGCTGCTGCTACTACTGCTGCTGCTCTGGCCAG                   TGCCAGOCGCCGGGGTGCTTCAAGGACATATCCCTGGGCAGCCAGTCACCCCGCACTGGGTCCTGGATGGACAAC               CCTGGCGCACCGTCAGCCTGGAGGAGCCGGTCTCGAAGCCAGACATGGGGCTGGTGGCCCTGGAGGCTGAAGGCC               AGGAGCTCCTGCTTGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCAGGATACATAGAAACCCACTACGGCCCAG               ATGGGCAGCCAGTGGTGCTGGCCCCCAACCACACGGATCATTGCCACTACCAAGGGCGAGTAAGGGGCTTCCCCG               ACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGATGAGTGGCCTGATCACCCTCAGCAGGAATGCCAGCTATTATC               TGCGTCCCTGGCCACCCCGGGGCTCCAAGGACTTCTCAACCCACGAGATCTTTCGGATGGAGCAGCTGCTCACCT               GGAAAGGAACCTGTGGCCACAGGGATCCTGGGAACAAAGCGGGCATGACCAGCCTTCCTGGTGGTCCCCAGAGCA               GGGGCAGGCGAGAAGCGCGCAGGACCCGGAAGTACCTGGAACTGTACATTGTGGCAGACCACACCCTGTTCTTGA               CTCGGCACCGAAACTTGAACCACACCAAACAGCGTCTCCTGGAAGTCGCCAACTACGTGGACCAGCTTCTCAGGA               CTCTGGACATTCAGGTGGCGCTGACCGGCCTGGAGGTGT3GACCGAGCGGGACCGCAGCCGCGTCACGCAGGACG               CCAACGCCACGCTCTGGGCCTTCCTGCAGTGGCGCCGGGGGCTGTGGCCGCAGCGGCCCCACGACTCCGCGCAGC               TGCTCACGGGCCGCGCCTTCCAGGGCGCCACAGTGGGCCTGGCGCCCGTCGAGGGCATGTGCCGCGCCGAGAGCT               CGGGAGGCGTGAGCACGGACCACTCGGAGCTCCCCATCGGCGCCGCAGCCACCATGGCCCATGAGATCGGCCACA               GCCTCGGCCTCAGCCACGACCCCGACGGCTGCTGCGTGGAGGCTGCGGCCGAGTCCGGAGGCTGCGTCATGGCTG               CGGCCACCGGGCACCCGTTTCCGCGCGTGTTCAGCGCCTGCAGCCGCCGCCAGCTGCGCGCCTTCTTCCGCAAGG               GGGGCGGCGCTTGCCTCTCCAATGCCCCGGACCCCGGACTCCCGGTGCCGCCGGCGCTCTGCGGGAACGGCTTCG               TGGAAGCGGGCGAGGAGTGTGACTGCGGCCCTGGCCAGGAGTGCCGCGACCTCTGCTGCTTTGCTCACAACTGCT               CGCTGCGCCCGGGGGCCCAGTGCGCCCACGGGGACTGCTGCGTGCGCTGCCTGCTAAAGCCGGCTGGAGCGCTGT               GCCGCCAGGCCATGACTGACTGTGACCTCCCTGAGTTTTGCACGGGCACCTCCTCCCACTGTCCCCCAGACGTTT               ACCTACTGGACGGCTCACCCTGTGCCAAGGGCAGTGGCTACTGCTGGGATGGCGCATGTCCCACGCTGGAGCAGC               AGTGCCAGCAGCTCTGGGGGCCTGGCTCCCACCCAGCTCCCGAGGCCTGTTTCCAGGTGGTGAACTCTGCGGGAG               ATGCTCATGGAAACTGCGGCCAGGACAGCGAGGGCCACTTCCTGCCCTGTGCAGGGAGGGATGCCCTGTGTGGGA               AGCTGCAGTGCCAGGGTGGAAAGCCCAGCCTGCTCGCACCGCACATGGTGCCAGTGGACTCTACCGTTCACCTAG               ATGGCCAGGAAGTGACTTGTCGGGGAGCCTTGGCACTCCCCAGTGCCCAGCTGGACCTGCTTGGCCTGGGCCTGG               TAGAGCCAGGCACCCAGTGTGGACCTAGAATGGTGTGCCAGAGCAGGCGCTGCAGGAAGAATGCCTTCCAGGAGC               TTCAGCGCTGCCTGACTGCCTGCCACAGCCACGGGGTTTGCAATAGCAACCATAACTGCCACTGTGCTCCAGGCT               GGGCTCCACCCTTCTGTGACAAGCCAGGCTTTGGTGGCAGCATGGACAGTGGCCCTGTGCAGGCTGAAAACCATG               ACACCTTCCTGCTGGCCATGCTCCTCAGCGTCCTGCTGCCTCTGCTCCCAGGCGCCGGCCTGGCCTGGTGTTGCT               ACCGACTCCCAGGAGCCCATCTGCAGCGATGCAGCTCGGGCTGCAGAAGGGACCCTGCGTGCAGTGGCCCCAAAG               ATGGCCCACACAGAGACCACCCCCTGGGCGGCGTTCACCCCATGGAGTTGGGCCCCACAGCCACTGGACAGCCCT               GGCCCCTGGACCCTGAGAACTCTCATGAGCCCAGCAGCCACCCTGAGAAGCCTCTGCCAGCAGTCTCGCCTGACC               CCCAAGGTGGTTCCCTTGCAGCCTGGGGCCCCAGTCCTTTAGGGGACAACATATCCTCCTCATTCTCAGCAGATC               AAGTCCAGATGCCAAGATCCTGCCTCTGTGGCGAACCCTGGGGAGGCCACGTGGGAAGGAAAGAGGGCTCTAAGA               GGGGAGGCCCCAGACTGGGGGAGAGGCCTGTCTGGAGCCCAGGATCACCTGGCTGTGCTGCAGAACTGGAGAAGA               GAAGCTCAGCAGAAAGGAGCTGGCATGGGGCCAACAGCAGAAAAGCAGGAGGCACGCAGAAG TGA   CTGGGAAGCA                   GGAGG                    
 
       [0220] The sequence of NOV7b was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0221] The DNA sequence and protein sequence for a novel stabilin-like gene were obtained by SeqCallingTM Technology and are reported here as NOV7b. These methods used to amplify NOV7b cDNA are described in Example 2.  
       [0222] The NOV7b polypeptide (SEQ ID NO: 24) encoded by SEQ ID NO: 23 is 895 amino acid residues in length and is presented using the one-letter amino acid code in Table 7D. The SignalP, Psort and/or Hydropathy results predict that NOV7b has a signal peptide and is likely to be localized extracellularly at the plasma membrane with a certainty of 0.4600. In alternative embodiments, a NOV7b polypeptide is located to the microbody (peroxisome) with a certainty of 0.1011, the endoplasmic reticulum (membrane) with a certainty of 0.1000, or the endoplasmic reticulum (lumen) with a certainty of 0.1000. The SignalP predicts a likely cleavage site for a NOV7b peptide between amino acid positions 29 and 30, i.e. at the dash in the sequence GAG-VL.  
               TABLE 7D                       Encoded NOV7b Protein Sequence                                    (SEQ ID NO:24)                 MGWRPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPVSKPDMGLVALEAEG               QELLLELEKNHRLLAPGYIETHYGPDGQPVVLAPNHTDHCHYQGRVRGFPDSWVVLCTCSGMSGLITLSRNASY               YLRPWPPRGSKDFSTHEIFRMEQLLTWKGTCGHRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTL               FLTRHRNLNHTKQRLLEVANYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATLWAFLQWRRGLWAQRPHD               SAQLLTGRAFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGCCVEAAAESGG               CVMAAATGHPFPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALCGNGFVEAGEECDCGPGQECRDLCC               FAHNCSLRPGAQCAHGDCCVRCLLKPAGALCRQAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCAKGSGYCWDGA               CPTLEQQCQQLWGPGSHPAPEACFQVVNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVP               VDSTVHLDGQEVTCRGALALPSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRCLTACHSHGVCNSN               HNCHCAPGWAPPFCDKPGFGGSMDSGPVQAENHDTFLLAMLLSVLLPLLPGAGLAWCCYRLPGAHLQRCSWGCR               RDPACSGPKDGPHRDHPLGGVHPMELGPTATGQPWPLDPENSHEPSSHPEKPLPAVSPDPQGGSLAAWGPSPLG               DNISSSFSADQVQMPRSCLCGEPWGGHVGRKEGSKRGGPRLGERPVWSPGSPGCAAELEKRSSAERSWHGANSR               KAGGTQK                  
 
       [0223] NOV7c  
       [0224] In an alternative embodiment, a NOV7 variant is NOV7c (alternatively referred to herein as CG50367-03), which includes the 2642 nucleotide sequence (SEQ ID NO: 25) shown in Table 7E. An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 3-5 and ending with a TGA codon at nucleotides 2625-2627. The start and stop codons of the open reading frame are highlighted in bold type. Putative untranslated regions are underlined and found upstream from the initiation codon and downstream from the termination codon.  
               TABLE 7E                       NOV7c Nucleotide Sequence                                    (SEQ ID NO:25)                   CT   ATG GGCTGGAGGCCCCGGAGAGCTCGGGGGACCCCGTTGCTGCTGCTGCTACTACTGCTGCTGCTCTGGCCAG               TGCCAGGCGCCGGGGTGCTTCAAGGACATATCCCTGGGCAGCCAGTCACCCCGCACTGGGTCCTGGATGGACAAC               CCTGGCGCACCGTCAGCCTGGAGGAGCCGGTCTCGAAGCCAGACATGGGGCTGGTGGCCCTGGAGGCTGAAGGCC               AGGAGCTCCTGCTTGAGCTGGAGAAGAACCACAGGCTGCTGGCCCCAGGATACATAGAAACCCACTACGGCCCAG               ATGGGCAGCCAGTGGTGCTGGCCCCCAACCACACGGATCATTGCCACTACCAAGGGCGAGTAAGGGGCTTCCCCG               ACTCCTGGGTAGTCCTCTGCACCTGCTCTGGGATGAGTGGCCTGATCACCCTCAGCAGGAATGCCAGCTATTATC               TGCGTCCCTGGCCACCCCGGGGCTCCAAGGACTTCTCAACCCACGAGATCTTTCGGATGGAGCAGCTGCTCACCT               GGAAAGGAACCTGTGGCCACAGGGATCCTGGGAACAAAGCGGGCATGACCAGCCTTCCTGGTGGTCCCCAGAGCA               GGGGCAGGCGAGAAGCGCGCAGGACCCGGAAGTACCTGGAACTGTACATTGTGGCAGACCACACCCTGTTCTTGA               CTCGGCACCGAAACTTGAACCACACCAAACAGCGTCTCCTGGAAGTCGCCAACTACGTGGACCAGCTTCTCAGGA               CTCTGGACATTCAGGTGGCGCTGACCGGCCTGGAGGTGTGGACCGAGCGGGACCGCAGCCGCGTCACGCAGGACG               CCAACGCCACGCTCTGGGCCTTCCTGCAGTGGCGCCGGGGGCTGTGGGCGCAGCGGCCCCACGACTCCGCGCAGC               TGCTCACGGGCCGCGCCTTCCAGGGCGCCACAGTGGGCCTGGCGCCCGTCGAGGGCATGTGCCGCGCCGAGAGCT               CGGGAGGCGTGAGCACGGACCACTCGGAGCTCCCCATCGGCGCCGCAGCCACCATGGCCCATGAGATCGGCCACA               GCCTCGGCCTCAGCCACGACCCCGACGGCTGCTGCGTGGAGGCTGCGGCCGAGTCCGGAGGCTGCGTCATGGCTG               CGGCCACCGGGCACCCGTTTCCGCGCGTGTTCAGCGCCTGCAGCCGCCGCCAGCTGCGCGCCTTCTTCCGCAAGG               GGGGCGGCGCTTGCCTCTCCAATGCCCCGGACCCCGGACTCCCGGTGCCGCCGGCGCTCTGCGGGAACGGCTTCG               TGGAAGCGGGCGAGGAGTGTGACTGCGGCCCTGGCCAGGAGTGCCGCGACCTCTGCTGCTTTGCTCACAACTGCT               CGCTGCGCCCGGGGGCCCAGTGCGCCCACGGGGACTGCTGCGTGCGCTGCCTGCTGAAGCCGGCTGGAGCGCTGT               GCCGCCAGGCCATGGGTGACTGTGACCTCCCTGAGTTTTGCACGGGCACCTCCTCCCACTGTCCCCCAGACGTTT               ACCTACTGGACGGCTCACCCTGTGCCAAGGGCAGTGGCTACTGCTGGGATGGCGCATGTCCCACGCTGGAGCAGC               AGTGCCAGCAGCTCTGGGGGCCTGGCTCCCACCCAGCTCCCGAGGCCTGTTTCCAGGTGGTGAACTCTGCGGGAG               ATGCTCATGGAAACTGCGGCCAGGACAGCGAGGGCCACTTCCTGCCCTGTGCAGGGAGGGATGCCCTGTGTGGGA               AGCTGCAGTGCCAGGGTGGAAAGCCCAGCCTGCTCGCACCGCACATGGTGCCAGTGGACTCTACCGTTCACCTAG               ATGGCCAGGAAGTGACTTGTCGGGGAGCCTTGGCACTCCCCAGTGCCCAGCTGGACCTGCTTGGCCTGGGCCTGG               TAGAGCCAGGCACCCAGTGTGGACCTAGAATGGTGTGCCAGAGCAGGCGCTGCAGGAAGAATGCCTTCCAGGAGC               TTCAGCGCTGCCTGACTGCCTGCCACAGCCACGGGGTTTGCAATAGCAACCATAACTGCCACTGTGCTCCAGGCT               GGGCTCCACCCTTCTGTGACAAGCCAGGCTTTGGTGGCAGCATGGACAGTGGCCCTGTGCAGGCTGAAAACCATG               ACACCTTCCTGCTGGCCATGCTCCTCAGCGTCCTGCTGCCTCTGCTCCCAGGCGCCGGCCTGGCCTGGTGTTGCT               ACCGACTCCCAGGAGCCCATCTGCAGCGATGCAGCTGGGGCTGCAGAAGGGACCCTGCGTGCAGTGGCCCCAAAG               ATGGCCCACACAGAGACCACCCCCTGGGCGGCGTTCACCCCATGGAGTTGGGCCCCACAGCCACTGGACAGCCCT               GGCCCCTGGACCCTGAGAACTCTCATGAGCCCAGCAGCCACCCTGAGAAGCCTCTGCCAGCAGTCTCGCCTGACC               CCCAAGCAGATCAAGTCCAGATGCCAAGATCCTGCCTCTGTGGCGAACCCTGGGGAGGCCACGTGGGAAGGAAAG               AGGGCTCTAAGAGGGGAGGCCCCAGACTGGGGGAGAGGCCTGTCTGGAGCCCAGGATCACCTGGCTGTGCTGCAG               AACTGGAGAAGAGAAGCTCAGCAGAAAGGAGCTGGCATGGGGCCAACAGCAGAAAAGCAGGAGGCACGCAGAAG T                   GA   CTGGGAAGCAGGA                   GG                    
 
       [0225] The sequence of NOV7c was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0226] The DNA sequence and protein sequence for a novel stabilin-like gene were obtained by SeqCallingTM Technology and are reported here as NOV7c. These methods used to amplify NOV7c cDNA are described in Example 2.  
       [0227] The NOV7c polypeptide (SEQ ID NO: 26) encoded by SEQ ID NO: 25 is 874 amino acid residues in length and is presented using the one-letter amino acid code in Table 7F. The SignalP, Psort and/or Hydropathy results predict that NOV7c has a signal peptide and is likely to be localized extracellularly at the plasma membrane with a certainty of 0.4600. In alternative embodiments, a NOV7c polypeptide is located to the microbody (peroxisome) with a certainty of 0.1000, the endoplasmic reticulum (membrane) with a certainty of 0.1000, or the endoplasmic reticulum (lumen) with a certainty of 0.1000. The SignalP predicts a likely cleavage site for a NOV7c peptide between amino acid positions 29 and 30, i.e. at the dash in the sequence GAG-VL.  
               TABLE 7F                       Encoded NOV7b Protein Sequence                                    (SEQ ID NO:26)                 MGWRPRRARGTPLLLLLLLLLLWPVPGAGVLQGHIPGQPVTPHWVLDGQPWRTVSLEEPVSKPDMGLVALEAEGQE               LLLELEKNHRLLAPGYIETHYGPDGQPVVLAPNHTDHCHYQGRVRGFPDSWVVLCTCSGMSGLITLSRNASYYLRP               WPPRGSKDFSTHEIFRMEQLLTWKGTCGHRDPGNKAGMTSLPGGPQSRGRREARRTRKYLELYIVADHTLFLTRHR               NLNHTKQRLLEVANYVDQLLRTLDIQVALTGLEVWTERDRSRVTQDANATLWAFLQWRRGLWAQRPHDSAQLLTGR               AFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLSHDPDGCCVEAAAESGGCVMAAATGHP               FPRVFSACSRRQLRAFFRKGGGACLSNAPDPGLPVPPALCGNGFVEAGEECDCGPGQECRDLCCFAHNCSLRPGAQ               CAHGDCCVRCLLKPAGALCRQAMGDCDLPEFCTGTSSHCPPDVYLLDGSPCAKGSGYCWDGACPTLEQQCQQLWGP               GSHPAPEACFQVVNSAGDAHGNCGQDSEGHFLPCAGRDALCGKLQCQGGKPSLLAPHMVPVDSTVHLDGQEVTCRG               ALALPSAQLDLLGLGLVEPGTQCGPRMVCQSRRCRKNAFQELQRCLTACHSHGVCNSNHNCHCAPGWAPPFCDKPG               FGGSMDSGPVQAENHDTFLLAMLLSVLLPLLPGAGLAWCCYRLPGAHLQRCSWGCRRDPACSGPKDGPHRDHPLGG               VHPMELGPTATGQPWPLDPENSHEPSSHPEKPLPAVSPDPQADQVQMPRSCLCGEPWGGHVGRKEGSKRGGPRLGE               RPVWSPGSPGCAAELEKRSSAERSWHGANSRKAGGTQK                  
 
       [0228] SNP variants of NOV7 are disclosed in Example 3.  
       [0229] NOV7 Clones  
       [0230] Unless specifically addressed as NOV7a, NOV7b, or NOV7c, any reference to NOV7 is assumed to encompass all variants.  
       [0231] The amino acid sequence of NOV7 has high homolgy to other proteins as shown in Table 7G.  
               TABLE 7G                          BLASTX Results from Patp Database for NOV7                             High   Smallest Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P (N)                                     patp: AAB47106   Second splice variant of MAPP -  Homo sapiens     4372   0.0       patp: AAB47105   First splice variant of MAPP -  Homo sapiens     3666   0.0       patp: AAB50935   ADAM protein #1 -  Homo sapiens     1790   1.6e−188       patp: AAB50942   ADAM gene #1 peptide #1 -  Homo sapiens     1790   6.6e−186       patp: AAW25716   Mouse beta meltrin protein   1753   2.1e−180                  
 
       [0232] In a search of sequence databases, it was found, for example, that the NOV7a nucleic acid sequence of this invention has 811 of 840 bases (96%) identical to a gb:GENBANK-ID:HSM801104|acc:AL117415.1 mRNA from  Homo sapiens  ( Homo sapiens  mRNA; cDNA DKFZp434K0521 (from clone DKFZp434KO521)). Further, the fill amino acid sequence of the disclosed NOV7a protein of the invention has 553 of 554 amino acid residues (99%) identical to, and 553 of 554 amino acid residues (99%) similar to, the 702 amino acid residue ptnr:TREMBLNEW-ACC:CAC16509 protein from  Homo sapiens  (Human) (DJ964F7.1 (NOVEL PROTEIN (DISINTEGRIN AND METALLOPROTEINASE))).  
       [0233] In a similar search of sequence databases, it was found, for example, that the NOV7b and NOV7c nucleic acid sequences have 1409 of 2252 bases (62%) identical to a gb:GENBANK-ID:XLU66003|acc:U66003.1 mRNA from  Xenopus laevis  ( Xenopus laevis  ADAM 13 mRNA, complete cds). Further, the fill amino acid sequence of the disclosed NOV7b and NOV7c proteins of the invention have 388 of 746 amino acid residues (52%) identical to, and 507 of 746 amino acid residues (67%) similar to, the 914 amino acid residue ptnr:SPTREMBL-ACC:O12960 protein from  Xenopus laevis  (African clawed frog) (ADAM 13).  
       [0234] Additional BLASTP results are shown in Table 7H.  
               TABLE 7H                          NOV7 BLASTP Results                                     Gene Index/       Length of           Expect       Identifier   Protein/Organism   aa   Identity (%)   Positives (%)   Value               CAC33154   SEQUENCE 3 FROM   812   785/811   789/811   0.0           PATENT WO0109293 -       (96%)   (97%)             Homo sapiens  (Human)       Q9BZ11   DJ964F7.1 (NOVEL   728   699/716   701/716   0.0           DISINTEGRIN AND       (97%)   (97%)           REPROLYSIN           METALLOPROTEINASE           FAMILY PROTEIN) -             Homo sapiens  (Human)       CAC33153   SEQUENCE 1 FROM   802   661/661   661/661   0.0           PATENT WO0109293 -       (100%)   (100%)             Homo sapiens  (Human)       AAK67164   ADAM33 -  Mus musculus     685   498/690   543/690   3.8e−280           (Mouse)       (72%)   (78%)       O12960   ADAM 13 -  Xenopus laevis     914   388/746   507/746   9.4e−211           (African clawed frog)       (52%)   (67%)                  
 
       [0235] A multiple sequence alignment is given in Table 7I, with the NOV7 protein of the invention being shown in lines 1, 2, and 3 in a ClustalW analysis comparing NOV7 with related protein sequences of Table 7H. 
 
 
 
 
       [0236] Domain results for NOV7 were collected from the Pfam database, and then identified by the Interpro domain accession number. The results are listed in Table 7J with the statistics and domain description. These results indicate that the NOV7 polypeptides have properties similar to those of other proteins known to contain these domains.  
               TABLE 7J                       Domain Analysis of NOV7                                                Score   E       PSSMs Producing Significant Alignments   (bits)   Value               Reprolysin (M12B) family zinc metalloprotease: domain 1 of 1,   306.6   3.1e−88       from 210 to 409                                 Reprolysin   kYiELvIVvDhgmytkygsdlnkirqrVhqivNlvNeiYrpqLNIrV   (SEQ ID NO:84)           +|+||+||+|+ ++   ++++++++++ ++++|+++  +++ | |+|       NOV7a   KYLELYIVADHTLFLTRHRNLNHTKQRLLEVANYVDQLLRT-LDIQV   (SEQ ID NO:22)                   vLvgLEIWsdgDkInvqsdandTLhsFgeWRetdLlkrksHDnAqLLtgi           +|++||+|+++|+  ++++++ ||  |++||+  |  +++|| |+||+++       NOV7a   ALTGLEVWTERDRSRVTQDANATLWAFLQWRRG-LWAQRPHDSAQLLTGR                   dfdgntiGaAyvggmCspkrSvGVvqdhspivllvAvtMAHELGHNLGmt            +++ ++|+|++ ++| +++|+||  ++++ +++ |++||||+||+||+       NOV7a   AFQGATVGLAPVEGMCRAESSGGVSTDHSELPIGAAATMAHEIGHSLGLS                   HDdknkdgCtCe...gggsCIMnpvassspskKkFSnCSkddyqkFltkq           ||++   +|+ +   ++++|+|++++++++++  || ||+ +++ |  ++       NOV7a   HDPD---GCCVEaaaESGGCVMAAATGHPFPR-VFSACSRRQLRAFFRKG                   kpqCLlNkP           +++|| |+|       NOV7a   GGACLSNAP                                 Pep_M12B_propep (Reprolysin family propeptide): domain 1 of 1,   112.3     9e−30       from 80 to 198                                 M12B Propep   hLeknrsllapdftvttYdedGtlvteepliqddHCyYqGyVeGypn   (SEQ ID NO:85)           |+++++++++++ +++|+++|+ +++ ++++ +||+|+|+|+|+++       NOV7a   ELEKNHRLLAPGYIETHYGPDGQPVVLAPNHT-DHCHYQGRVRGFPD   (SEQ ID NO:22)                   SaVslSTCsGgLRGilqlenlsYgIEPle..ssdgf.eHiiYqiendkte           |+| ++||+|  +++    + +|++ | +++++ ++++| +++++++ +       NOV7a   SWVVLCTCSGMSGLITLSRNASYYLRPWPprGSKDFsTHEIFRMEQLLTW                   pspcgecgslststdssygirsasp           +++++++++ +  +  + + +  ++       NOV7a   KGTCGHRDPGN-KAGMTSLPGGPQ                  
 
       [0237] The NOV7 disclosed in this invention is expressed in at least the following tissues: Ascending Colon, Cervix, Heart, Liver, Lymph node, Mammary gland/Breast, Ovary, Peripheral Blood, Placenta, Retina, Skin, Stomach, Testis, Uterus, and Whole Organism. This information was derived by determining the tissue sources of the sequences that were included in the invention including but not limited to SeqCalling sources, Public EST sources, Literature sources, and/or RACE sources.  
       [0238] The protein similarity information, expression pattern, and map location for the ADAM13-like protein and nucleic acid disclosed herein suggest that this protein may have important structural and/or physiological functions characteristic of the ADAM protein family. Therefore, the nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, the compositions of the present invention will have efficacy for treatment of patients suffering from: Xerostomia, Scleroderma, Hypercalceimia, Ulcers, Von Hippel-Lindau (VHL) syndrome, Cirrhosis,Transplantation, Cirrhosis, Inflammatory bowel disease, Diverticular disease, Hirschsprung&#39;s disease, Crohn&#39;s Disease, Appendicitis, Endometriosis,Fertility, 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, Aneurysm, Fibromuscular dysplasia, Stroke, Bleeding disorders, Hemophilia, hypercoagulation, Idiopathic thrombocytopenic purpura, autoimmume disease,allergies, immunodeficiencies, Graft vesus host, Anemia, Ataxia-telangiectasia, Lymphedema, Allergies, and Tonsilitis and other diseases, disorders and conditions of the like.  
       [0239] The novel nucleic acid encoding the ADAM13-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV7 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV7 epitope is from about amino acids 40 to 60. In another embodiment, a contemplated NOV7 epitope is from about amino acids 70 to 125. In alternative embodiments, contemplated NOV7 epitopes include from about amino acids 140 to 210, 220 to 250, 260 to 310, 320 to 360, 370 to 410, 420 to 460, 470 to 610, 620 to 700, and 710 to 910.  
       [0240] NOV8  
       [0241] Yet a further NOVX protein of the invention, referred to herein as NOV8 (alternatively referred to as CG50321-01), is a leucine-rich repeat containing an F-box protein-like protein.  
       [0242] F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 amino acid motif, the F box (so named because cyclin F was one of the first proteins in which this motif was identified). Some F-box proteins are known to be critical for the controlled degradation of cellular regulatory proteins. In fact, F-box proteins are one of the four subunits of ubiquitin protein ligases called SCFs. SCF ligases bring ubiquitin conjugating enzymes (either Ubc3 or Ubc4) to substrates that are specifically recruited by the different F-box proteins. The need for high substrate specificity and the large number of known F-box proteins in yeast and worms suggest the existence of a large family of mammalian F-box proteins. Some of these proteins contain WD-40 domains or leucine-rich repeats; others contain either different protein-protein interaction modules or no recognizable motifs. They named the F-box proteins that contain WD-40 domains Fbws, those containing leucine-rich repeats, Fbls, and the remaining ones Fbxs. The marked differences in F-box gene expression in human tissues is exemplar of their distinct role in ubiquitin-dependent protein degradation.  
       [0243] The NOV8 protein predicted here is localized extracellularly at the plasma membrane. Therefore, it is likely that this leucine-rich containing F-box protein-like protein is accessible to a diagnostic probe, and for the various therapeutic applications described herein.  
       [0244] The NOV8 protein disclosed in this invention maps to chromosome 17. This information was assigned using OMIM, the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0245] The NOV8 nucleic acid (SEQ ID NO: 27) of 1307 nucleotides encodes a novel leucine-rich containing F-box protein-like protein and is shown in Table 8A. An open reading frame for the mature protein was identified beginning with a ATG initiation codon at nucleotides 17-19 and ending with a TGA codon at nucleotides 1283-1285. Putative untranslated regions upstream from the start codon and downstream from the termination codon are underlined in Table 8A. The start and stop codons are in bold letters.  
               TABLE 8A                       NOV8 Nucleotide Sequence                                    (SEQ ID NO:27)                   CAAGAGCAGGTTTGAG   ATG TTCTCAAATAGTGATGAAGCTGTAATCAATAAAAAACTTCCCAAAGAACTCCTGTT               ACGGATATTTTCTTTTCTAGATGTTGTTACCCTGTGCCGCTGTGCTCAGGTCTCCAGGGCCTGGAATGTTCTGGC               TCTGGATGGCAGTAACTGGCAGCGAATTGACCTATTTGATTTCCAGAGGGATATTGAGGGCCGAGTAGTGGAGAA               TATTTCAAAACGATGTGGGGGCTTTTTACGAAAGTTAAGTCTTCGTGGATGTCTTGGAGTGGGAGACAATGCATT               AAGAACCTTTGCACAAAACTGCAGGAACATTGAAGTACTGAATCTAAATGGGTGTACAAAGACAATAGACGCTAC               ATGTACTAGCCTTAGCAAGTTCTGTTCCAAACTCAGGCACCTTGACTTGGCTTCCTGTACATCAATAACAAACAT               GCCTCTAAAAGCTCTGAGTGAGGGATGTCCACTGTTGGAGCAGTTGAACATTTCCTGGTGTGACCAAGTAACCAA               GGATGGCATTCAAGCACTAGTGAGGGGCTGTGGGGGTCTCAAGGCCTTATTCTTAAAAGGCTGCACGCAGCTAGA               AGATGAAGCTCTCAAGTACATAGGTGCACACTGCCCTGAACTGGTGACTTTGAACTTGCAGACTTGCTTGCAAAT               CACAGATGAAGGTCTCATTACTATATGCAGAGGGTGCCATAAGTTACAATCCCTTTGTGCCTCTGGCTGCTCCAA               CATCACAGATGCCATCCTGAATGCTCTAGGTCAGAACTGCCCACGGCTTAGAATATTGGAAGTGGCAAGATGTTC               TCAATTAACAGATGTGGGCTTTACCACTCTAGCCAGGAATTGCCATGAACTTGAAAAGATGGACCTGGAAGAGTG               TGTTCAGATAACAGATAGCACATTAATCCAACTTTCTATACACTGTCCTCGACTTCAAGTATTGAGTCTGTCTCA               CTGTGAGCTGATCACAGATGATGGAATTCGTCACCTGGGGAATGGGGCCTGCGCCCATGACCAGCTGGAGGTGAT               TGAGCTGGACAACTGCCCACTAATCACAGATGCATCCCTGGAGCACTTGAAGAGCTGTCATAGCCTTGAGCGGAT               AGAACTCTATGACTGCCAGCAAATCACACGGGCTGGAATCAAGAGACTCAGGACCCATTTACCCAATATTAAAGT               CCACGCCTACTTCGCACCTGTCACTCCACCCCCATCAGTAGGGGGCAGCAGACAGCGCTTCTGCAGATGCTGCAT               CATCCTA TGA   CAATGGAGGTGGTCAACCTTGG                    
 
       [0246] The sequence of NOV8 was derived by laboratory cloning of cDNA fragments covering the full length and/or part of the DNA sequence of the invention, and/or by in silico prediction of the full length and/or part of the DNA sequence of the invention from public human sequence databases.  
       [0247] The cDNA coding for the NOV8 sequence was cloned by the polymerase chain reaction (PCR). PCR primers were designed based on in silico predictions of the full length or some portion (one or more exons) of the cDNA/protein sequence of the invention. The DNA sequence and protein sequence for a novel leucine-rich containing F-Box protein-like gene were obtained by exon linking, or SeqCalling™ Technology and are reported here as NOV8. These primers and methods used to amplify NOV8 cDNA are described in Example 2.  
       [0248] The NOV8 polypeptide (SEQ ID NO: 28) encoded by SEQ ID NO: 27 is 422 amino acid residues in length and is presented using the one-letter amino acid code in Table 8B. The SignalP, Psort and/or Hydropathy results predict that NOV8 has a signal peptide and is likely to be localized extracellularly at the plasma membrane with a certainty of 0.6500. In alternative embodiments, a NOV8 polypeptide is located to the cytoplasm with a certainty of 0.4500, the microbody (peroxisome) with a certainty of 0.3000, or the mitochondrial matrix space with a certainty of 0.1000.  
               TABLE 8B                       Encoded NOV8 Protein Sequence                                    (SEQ ID NO:28)                 MFSNSDEAVINKKLPKELLLRIFSFLDVVTLCRCAQVSRAWNVLALDGSNWQRIDLFDFQRDIEGRVVENISKR               CGGFLRKLSLRGCLGVGDNALRTFAQNCRNIEVLNLNGCTKTIDATCTSLSKFCSKLRHLDLASCTSITNMPLK               ALSEGCPLLEQLNISWCDQVTKDGIQALVRGCGGLKALFLKGCTQLEDEALKYIGAHCPELVTLNLQTCLQITD               EGLITICRGCHKLQSLCASGCSNITDAILNALGQNCPRLRILEVARCSQLTDVGFTTLARNCHELEKMDLEECV               QITDSTLIQLSIHCPRLQVLSLSHCELITDDGIRHLGNGACAHDQLEVIELDNCPLITDASLEHLKSCHSLERI               ELYDCQQITRAGIKRLRTHLPNIKVHAYFAPVTPPPSVGGSRQRFCRCCI               IL                  
 
       [0249] SNP variants of NOV8 are disclosed in Example 3.  
       [0250] The amino acid sequence of NOV8 has high homology to other proteins as shown in Table 8C.  
               TABLE 8C                          BLASTX Results from Patp Database for NOV8                                 Smallest Sum       Sequences Producing High-Scoring Segment Pairs:   High Score   Prob P (N)                                     patp: AAB48290   Human ZF1 protein   1819   2.1e−187       patp: AAB92961   Human protein sequence   1818   2.7e−187       patp: AAB92791   Human protein sequence   1817   3.4e−187       patp: AAY83090   F-box protein FBP-22 -  Homo sapiens     1786   6.5e−184       patp: AAY02274 A   F-box protein sequence -  Homo sapiens     1562   3.6e−160                  
 
       [0251] In a search of sequence databases, it was found, for example, that the NOV8 nucleic acid sequence of this invention has 737 of 801 bases (92%) identical to a gb:GENBANK-ID:AF182443|acc:AF182443.1 mRNA from  Rattus norvegicus  ( Rattus norvegicus  F-box protein FBL2 (FBL2) mRNA, complete cds). Further, the full amino acid sequence of the disclosed NOV8 protein of the invention has 328 of 422 amino acid residues (77%) identical to, and 375 of 422 amino acid residues (88%) similar to, the 423 amino acid residue ptnr:SPTREMBL-ACC:Q9UK27 protein from  Homo sapiens  (Human) (LEUCINE-RICH REPEATS CONTAINING F-BOX PROTEIN FBL3).  
       [0252] Additional BLASTP results are shown in Table 8D.  
               TABLE 8D                          NOV8 BLASTP Results                                     Gene Index/       Length of           Expect       Identifier   Protein/Organism   aa   Identity (%)   Positives (%)   Value               AAH07557   RIKEN CDNA 2610511F20   422   420/422   420/422   2.0e−230           GENE -  Homo sapiens         (99%)   (99%)           (Human)       Q9CZV8   2610511F20RIK PROTEIN -   422   416/422   417/422   1.1e−227             Mus musculus  (Mouse)       (98%)   (98%)       Q9UK27   LEUCINE-RICH   423   328/422   375/422   1.6e−187           REPEATS CONTAINING       (77%)   (88%)           F-BOX PROTEIN FBL3 -             Homo sapiens  (Human)       Q9UKA5   F-BOX PROTEIN FBL2 -   425   328/422   375/422   2.7e−187             Homo sapiens  (Human)       (77%)   (88%)       Q9NVQ8   CDNA FLJ10576 FIS,   423   327/422   375/422   3.4e−187           CLONE NT2RP2003329,       (77%)   (88%)           WEAKLY SIMILAR TO           PUTATIVE ADENYLATE           CYCLASE           REGULATORY PROTEIN -             Homo sapiens  (Human)                  
 
       [0253] A multiple sequence alignment is given in Table 8E in a ClustalW analysis comparing NOV8 with related protein sequences disclosed in Table 8D. 
 
 
 
       [0254] Domain results for NOV8 were collected from BLAST sample domains found in the Smart and Pfam collections, and then identified by the Interpro domain accession number. The results are listed in Table 8F with the statistics and domain description. These results indicate that the NOV8 polypeptide has properties similar to those of other proteins known to contain these domains and similar to the properties of these domains.  
               TABLE 8F                       Domain Analysis of NOV8                                                Score   E       PSSMs Producing Significant Alignments   (bits)   Value               F-box: domain 1 of 2, from 9 to 56   29.3   9e−05                                 F-box   fsllrLPddllekilsrLplkdllslskvskkfrslvdsl.ldv.kl   (SEQ ID NO:91)                 || ++++ ++++|+  ++++++++++ ++ ++ +++++ ++       NOV8   VINKKLPKELLLRIFSFLDVVTLCRCAQVSRAWNVLALDGsNWQrID   (SEQ ID NO:28)                   l           +       NOV8   L                  
 
       [0255] The Leucine-rich containing F-Box protein-like protein disclosed in this invention is expressed in at least the following tissues: Adrenal Gland, Bladder, Bone marrow, Brain (fetal), Brain (whole), Brain (amygdala), Brain (cerebellum), Brain (hippocampus), Brain (thalamus), Cerebral Cortex, Colorectal, Endothelial cells, Heart, Kidney, Kidney (fetal), Liver, Liver (fetal), Lymph node, Lung, Lung (fetal), Mammary gland, Ovary, Pancreas, Pituitary gland, Placenta, Prostate, Salivary gland, Skeletal Muscle, Small intestine, Spinal cord, Spleen, Stomach, Testis, Trachea, Thymus, Thyroid, Uterus, and several cancer cell lines including Breast ca. (except Breast ca. MDA-N), CNS ca, Colon ca., Gastric ca., Liver ca., Melanoma, Ovarian ca., Pancreatic ca., Prostate ca, and Renal ca. at a measurably higher level than the following tissues: Adipose and one cancer cell line Breast ca. MDA-N. Furthermore, the expression level is even higher in two particular cancer cell lines: Lung ca. (non-s.cl) NCI-H522 and Gastric ca. (liver met) NCI-N87.  
       [0256] The protein similarity information, expression pattern, and map location for the leucine-rich repeats containing F-Box protein-like protein and nucleic acid disclosed herein suggest that this protein may have important structural and/or physiological functions characteristic of the F-Box protein family. Therefore, the NOV8 nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, since the protein of the invention is ubiquitously expressed in many tissues, the compositions of the present invention will have efficacy for treatment of patients suffering from diseases associated with these tissues. Also since the expression level of the invention is much higher in two particular cancer cell lines: Lung ca. (non-s.cl) NCI-H522 and Gastric ca. (liver met) NCI-N87, the invention may be useful in diagnosis and treatment of these cancers.  
       [0257] The novel nucleic acid encoding the leucine-rich repeats containing F-Box protein-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods These 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 NOV8 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV8 epitope is from about amino acids 10 to 15. In another embodiment, a contemplated NOV8 epitope is from about amino acids 40 to 80. In other specific embodiments, contemplated NOV8 epitopes are from about amino acids 85 to 110, 120 to 140, 148 to 150, 155 to 180, 190 to 210, 225 to 230, 240 to 250, 253 to 260, 262 to 270, 275 to 300, 325 to 345, 350 to 400, and 405 to 420.  
       [0258] NOV9  
       [0259] Still yet a further NOVX protein of the invention, referred to herein as NOV9 (alternatively referred to as CG55902-01), is a steroid binding-like protein.  
       [0260] Steroid binding proteins are involved in reproductive behavior, cell cycle progression and various important physiologic pathologies.  
       [0261] The NOV9 protein disclosed herein is predicted to localize extracellularly. Therefore, it is likely that this steroid binding protein-like protein is accessible to a diagnostic probe, and for the various therapeutic applications described herein.  
       [0262] The NOV9 protein disclosed in this invention maps to chromosome 12. This information was assigned using OMIM, the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0263] The NOV9 nucleic acid (SEQ ID NO: 29) of 499 nucleotides encodes a novel steroid binding protein-like protein and is shown in Table 9A. An open reading frame for the mature protein was identified beginning with a ATG initiation codon at nucleotides 19-21 and ending with a TGA codon at nucleotides 442-444. Putative untranslated regions upstream from the start codon and downstream from the termination codon are underlined in Table 9A. The start and stop codons are in bold letters.  
               TABLE 9A                       NOV9 Nucleotide Sequence                                    (SEQ ID NO:29)                   TTCACTGTGGTGGGCCCC   ATG CCAGGGCAGTGGCTGCAGCAGCTGGCAGTGCTAGTCCTGATTCTGGTGCTAGCCT               GGGGGGCTGGTCTACTATGGCAGGAGAAGGATCAGCCCATCTATTTGGCAGTGAAGGGAGTGGGGCTTGATGTCAC               CTCTGGAAAGGGGTTTTATGGACAAAGAGCCCCCTACAATGCCTTGACCAGGAAGGACTCTGCTAGAGGGGTAGCC               AAGGTGTCCTTGGATCATGTAGACCTTACCTGTGACACAACAGGTCTCATAGCCAAGAAGTTGGAGTCCATGGATG               ATGTCTTCACCAGTGTGTACAAAGCCAAACACCCAATTGTCAGCTACAGGGCTCAGACAATTCTCAATGAGTTTGG               CAGCCCCAACCTGGACTTCAAGGCTGAAGACCAGCCCCTTTTTGACAAGAAGGAGGGGTTC TGA   GGTTTCATCTGC                   AGGAGCAGGTTTTTGGGAGAGTGAGGTAGGAAGACATTCCAGC                    
 
       [0264] The sequence of NOV9 was derived by laboratory cloning of cDNA fragments covering the full length and/or part of the DNA sequence of the invention, and/or by in silico prediction of the full length and/or part of the DNA sequence of the invention from public human sequence databases.  
       [0265] The NOV9 polypeptide (SEQ ID NO: 30) encoded by SEQ ID NO: 29 is 141 amino acid residues in length and is presented using the one-letter amino acid code in Table 9B. The SignalP, Psort and/or Hydropathy results predict that NOV9 has a signal peptide and is likely to be localized extracellularly with a certainty of 0.8200. In alternative embodiments, a NOV9 polypeptide is located to the microbody peroxisome) with a certainty of 0.1274, the endoplasmic reticulum (membrane) with a certainty of 0.1000, or the endoplasmic reticulum (lumen) with a certainty of 0.1000.  
               TABLE 9B                       Encoded NOV9 Protein Sequence                                    (SEQ ID NO:30)                 MPGQWLQQLAVLVLILVLAWGAGLLWQEKDQPIYLAVKGVGLDVTSGKGFYGQRAPYNALTRKDSARGVAKV               SLDHVDLTCDTTGLIAKKLESMDDVFTSVYKAKHPIVSYRAQTILNEFGSPNLDFKAEDQPLFDKKEGF                  
 
       [0266] The amino acid sequence of NOV9 has high homology to other proteins as shown in Table 9C.  
               TABLE 9C                          BLASTX Results from Patp Database for NOV9                                 Smallest           High   Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P (N)                                     patp: AAY94866   Human protein clone HP10557   427   2.2e−42       patp: AAB98322   Human PA27 protein   427   4.6e−42       patp: AAY76019   Rat dermal papilla protein DP3   412   6.6e−41       patp: AAB55958   Skin cell protein   412   6.6e−41       patp: AAB98325   Human ortholog of r0v0-176.7A (PA27) protein sequence   240   8.7e−23                  
 
       [0267] In a search of sequence databases, it was found, for example, that the NOV9 nucleic acid sequence of this invention has 392 of 484 bases (80%) identical to a gb:GENBANK-ID:AF173937|acc:AF173937.1 mRNA from  Homo sapiens  ( Homo sapiens  secreted protein of unknown function (SPUF), mRNA, complete cds). Further, the full amino acid sequence of the disclosed protein of the invention has 85 of 115 amino acid residues (73%) identical to, and 96 of 115 amino acid residues (83%) similar to, the 172 amino acid residue ptnr:SPTREMBL-ACC:Q9UMX5 protein from  Homo sapiens  (Human) (SECRETED PROTEIN OF UNKNOWN FUNCTION).  
       [0268] Additional BLASTP results are shown in Table 9D.  
               TABLE 9D                          NOV9 BLASTP Results                                     Gene Index/       Length of       Positives   Expect       Identifier   Protein/Organism   aa   Identity (%)   (%)   Value               Q9UMX5   SECRETED PROTEIN OF   172   85/115   96/115   2.8e−42           UNKNOWN FUNCTION -       (73%)   (83%)             Homo sapiens  (Human)       Q9CQ45   1110060M21RIK   171   84/115   96/115   2.3e−39           PROTEIN -  Mus musculus         (73%)   (83%)           (Mouse)       Q9SK39   PUTATIVE STEROID   100   30/82   53/82   3.5e−11           BINDING PROTEIN -       (36%)   (64%)             Arabidopsis thaliana             (Mouse-ear cress)       Q9FVZ7   PUTATIVE STEROID   232   32/94   54/94   6.4e−09           MEMBRANE BINDING       (34%)   (57%)           PROTEIN - Oryza sativa           (Rice)                  
 
       [0269] A multiple sequence alignment is given in Table 9E in a ClustalW analysis comparing NOV9 with related protein sequences disclosed in Table 9D. 
 
 
 
       [0270] Domain results for NOV9 were collected from BLAST sample domains found in the Smart and Pfam collections, and then identified by the Interpro domain accession number. The results are listed in Table 9F with the statistics and domain description. These results indicate that the NOV9 polypeptide has properties similar to those of other proteins known to contain these domains and similar to the properties of these domains.  
               TABLE 9F                       Domain Analysis of NOV9                                                Score   E       PSSMs Producing Significant Alignments   (bits)   Value               Steroid Binding Domain (SBD): domain 1 of 1, from 28 to   52.2   1.2e−11       113                                 SBD   DFTpeELrkYDGsdedkpIylAikGkVYDVtrGrkFYGPgGPYslFA   (SEQ ID NO:96)                       ++ +++|++|++|   ||++|+ |||  +||++++       NOV9   ------------EK-DQPIYLAVKGVGLDVTSGKGFYGQRAPYNALT   (SEQ ID NO:30)                   GrDASRaLatmsfDeedlkdsDeEidDlsdLsadeleaLreWetk.FkaK            +|+ |++++ ++|  +++       |+++| ++ +++ ++++++ +++|       NOV9   RKDSARGVAKVSLDHVDLT------CDTTGLIAKKLESMDDVFTSvYKAK                   YpvVGrLi            ++| +       NOV9   HPIVSYRA                  
 
       [0271] The steroid binding protein-like protein disclosed in this invention is expressed in a variety of tssues.  
       [0272] The protein similarity information, expression pattern, and map location for the steroid binding protein-like protein and nucleic acid disclosed herein suggest that this protein may have important structural and/or physiological functions characteristic of the steroid binding protein family. Therefore, the NOV9 nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, the compositions of the present invention will have efficacy for treatment of patients suffering from: cancer, cataracts, obesity, diabetes, hyperlipidemia, infertility, inflammation, CNS disorders and other diseases, disorders and conditions of the like.  
       [0273] The novel nucleic acid encoding the steroid binding protein-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV9 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV9 epitope is from about amino acids 25 to 37. In another embodiment, a contemplated NOV9 epitope is from about amino acids 42 to 78. In other specific embodiments, contemplated NOV9 epitopes are from about amino acids 81 to 92, and 95 to 135.  
       [0274] NOV10  
       [0275] Another NOVX protein of the invention, referred to herein as NOV10, includes two novel steroid dehydrogenase-like proteins. The disclosed proteins have been named NOV10a and NOV10b.  
       [0276] Steroid dehydrogenase enzymes influence mammalian reproduction, hypertension, neoplasia, and digestion. The three-dimensional structures of steroid dehydrogenase enzymes reveal the position of the catalytic triad, a possible mechanism of keto-hydroxyl interconversion, a molecular mechanism of inhibition, and the basis for selectivity.  
       [0277] The NOV10 proteins disclosed here are predicted to localize at the plasma membrane. Therefore, it is likely that these proteins are accessible to a diagnostic probe, and for the various therapeutic applications described herein.  
       [0278] The NOV10 proteins in this invention map to chromosome 16. This information was assigned using OMIM, the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0279] NOV10a  
       [0280] In one embodiment, a NOV10 variant is NOV10a (alternatively referred to herein as CG50307-01), which encodes a novel steroid dehydrogenase-like protein and includes the 1831 nucleotide sequence (SEQ ID NO: 31) shown in Table 10A. An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 183-185 and ending with a TGA codon at nucleotides 1173-1175. Putative untranslated regions downstream from the termination codon and upstream from the initiation codon are underlined in Table 10A, and the start and stop codons are in bold letters.  
               TABLE 10A                       NOV10a Nucleotide Sequence                                        (SEQ ID NO:31)                           ACCGGTTTGGAAGACTTTGCCGGCCTGCAGGACACATGATGACATTGGAC                       CCACCCTCCCCAGCTCGGAGTCTTTAACTCAGTCACATCTACGGAGTCCC                   TTTGGCCACATAAGATTGGCCTTAAGAGAAGGACGGAGCCACATACTGCT                   GACGGCCCAGAACTGGCAGAGAGAAGGTTGCC   ATG GCTGCTGTTGACAGT               TTCTACCTCTTGTACAGGGAAATCGCCAGGTCTTGCAATTGCTATATGGA               AGCTCTAGCTTTGGTTGGAGCCTGGTATACGGCCAGAAAAAGCATCACTG               TCATCTGTGACTTTTACAGCCTGATCAGGCTGCATTTTATCCCCCGCCTG               GGGAGCAGAGCAGACTTGATCAAGCAGTATGGAAGATGGGCCGTTGTCAG               CGGTGCAACAGATGGGATTGGAAAAGCCTACGCTGAAGAGTTAGCAAGCC               GAGGTCTCAATATAATCCTGATTAGTCGGAACGAGGAGAAGTTGCAGGTT               GTTGCTAAAGACATAGCCGACACGTACAAAGTGGAAACTGATATTATAGT               TGCGGACTTCAGCAGCGGTCGTGAGATCTACCTTCCAATTCGAGAAGCCC               TGAAGGACAAAGACGTTGGCATCTTGGTAAATAACGTGGGTGTGTTTTAT               CCCTACCCGCAGTATTTCACTCAGCTGTCCGAGGACAAGCTCTGGGACAT               CATAAATGTGAACATTGCCGCCGCTAGTTTGATGGTCCATGTTGTGTTAC               CGGGAATGGTGGAGAGAAAGAAAGGTGCCATCGTCACGATCTCTTCTGGC               TCCTGCTGCAAACCCACTCCTCAGCTGGCTGCATTTTCTGCTTCTAAGGC               TTATTTAGACCACTTCAGCAGAGCCTTGCAATATGAATATGCCTCTAAAG               GAATCTTTGTACAGAGTCTAATCCCTTTCTATGTAGCCACCAGCATGACA               GCACCCAGCAACTTTCTGCACAGGTGCTCGTGGTTGGTGCCTTCGCCAAA               AGTCTATGCACATCATGCTGTTTCTACTCTTGGGATTTCCAAAAGGACCA               CAGGATATTGGTCCCATTCTATTCAGTTTCTTTTTGCACAGTATATGCCT               GAATGGCTCTGGGTGTGGGGAGCAAATATTCTCAACCGTTCACTACGTAA               GGAAGCCTTATCCTGCACAGCC TGA   GTCTGGATGGCCACTTGAGAAGTTT                   TGCCAACTCCTGGGAACCTCGATATTCTGACATTTGGAAAAACACATTTA                   ATTTATCTCCTGTGTTTCATTGCTGATTATTCAGCATACTGTTGATTCGT                   CATTTGCAAAACACACATAATACCGTCAGAGTGCTGTGAAAAACCTTAAG                   GGTGTGTGGATGGCACAGGATCAATAATGCCTGAGGCTGATTGACGACAT                   CTACATTTCAGTGCTTTTTCCCTAAGCTGTTTGAAAGTTACGCTTTTCTG                   TTGTTCTAGAGCCACAGCAGTCTAATATTGAAATATAATATGATTGTCAG                   GTCTTATAATTTCAGATGTTGTTTTTTAAGGGAAATTGACCATTTCACTA                   GAGGAGTTGTGCTGGTTTTTACATGTGCATCAAGGAAAGACTACTGGAAA                   AGTATTTATTTTGGTAACTAAGATTGCTGGCTACTATTAGGGACACACTC                   CGGGCTGTTTGGTATAGCTCTACCTGGTTTGACTATCTGTCATGGAAATG                   CTGCCTTCCACTGGTTTTTCCTTTGAGACGGGGTGTGTGCCTGGGTTGTG                   GGGCCCTTGGGCCCCTTTTTTTTGGTGCCCCTTCTTCCACCCACTTTCGG                   CCCGCGGGCCCCCTGGCGCTCTGGGTTTCCC                    
 
       [0281] The sequence of NOV10a was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0282] The DNA sequence and protein sequence for a novel transmembrane-like gene were obtained by SeqCallingTM Technology and are reported here as NOV10a. These methods used to amplify NOV10a cDNA are described in Example 2.  
       [0283] The NOV10a polypeptide (SEQ ID NO: 32) encoded by SEQ ID NO: 31 is 330 amino acid residues in length and is presented using the one-letter amino acid code in Table 10B. The SignalP, Psort and/or Hydropathy results predict that NOV10a has no known signal peptide and is likely to be localized at the plasma membrane with a certainty of 0.7000. In alternative embodiments, a NOV10a polypeptide is located to the mitochondrial inner membrane with a certainty of 0.6577, the microbody (peroxisome) with a certainty of 0.4556, or the mitochondrial matrix space with a certainty of 0.2792.  
               TABLE 10B                       Encoded NOV10a Protein Sequence                                        (SEQ ID NO:32)                         MAAVDSFYLLYREIARSCNCYMEALALVGAWYTARKSTTVICDFYSLIRL                   HFIPRLGSRADLIKQYGRWAVVSGATDGIGKAYAEELASRGLNIILISRN               EEKLQVVAKDIADTYKVETDIIVADFSSGREIYLPIREALKDKDVGILVN               NVGVFYPYPQYFTQLSEDKLWDIINVNIAAASLMVHVVLPGMVERKKGAI               VTISSGSCCKPTPQLAAFSASKAYLDHFSRALQYEYASKGIFVQSLIPFY               VATSMTAPSNFLHRCSWLVPSPKVYAHHAVSTLGISKRTTGYWSHSIQFL               FAQYMPEWLWVWGANILNRSLRKEALSCTA                  
 
       [0284] NOV10b  
       [0285] In an alternative embodiment, a NOV10 variant is NOV10b (alternatively referred to herein as CG50307-02), which includes the 1152 nucleotide sequence (SEQ ID NO: 33) shown in Table 10C. An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 97-99 and ending with a TGA codon at nucleotides 1087-1089. The start and stop codons of the open reading frame are highlighted in bold type. Putative untranslated regions are underlined and found upstream from the initiation codon and downstream from the termination codon.  
               TABLE 10C                       NOV10b Nucleotide Sequence                                        (SEQ ID NO:33)                           ATCTACGGAGTCCCTTTGGCCACATAAGATTGGCCTTAAGAGAAGGACGG                       AGCCACATACTGCTGACGGCCCAGAACTGGCAGAGAGAAGGTTGCC   ATG G               CTGCTGTTGACAGTTTCTACCTCTTGTACAGGGAAATCGCCAGGTCTTGC               AATTGCTATATGGAAGCTCTAGCTTTGGTTGGAGCCTGGTATACGGCCAG               AAAAAGCATCACTGTCATCTGTGACTTTTACAGCCTGATCAGGCTGCATT               TTATCCCCCGCCTGGGGAGCAGAGCAGACTTGATCAAGCAGTATGGAAGA               TGGGCCGTTGTCAGCGGTGCAACAGATGGGATTGGAAAAGCCTACGCTGA               AGAGTTAGCAAGCCGAGGTCTCAATATAATCCTGATTAGTCGGAACGAGG               AGAAGTTGCAGGTTGTTGCTAAAGACATAGCCGACACGTACAAAGTGGAA               ACTGATATTATAGTTGCGGACTTCAGCAGCGGTCGTGAGATCTACCTTCC               AATTCGAGAAGCCCTGAAGGACAAAGACGTTGGCATCTTGGTAAATAACG               TGGGTGTGTTTTATCCCTACCCGCAGTATTTCACTCAGCTGTCCGAGGAC               AAGCTCTGGGACATCATAAATGTGAACATTGCCGCCGCTAGTTTGATGGT               CCATGTTGTGTTACCGGGAATGGTGGAGAGAAAGAAAGGTGCCATCGTCA               CGATCTCTTCTGGCTCCTGCTGCAAACCCACTCCTCAGCTGGCTGCATTT               TCTGCTTCTAAGGCTTATTTAGACCACTTCAGCAGAGCCTTGCAATATGA               ATATGCCTCTAAAGGAATCTTTGTACAGAGTCTAATCCCTTTCTATGTAG               CCACCAGCATGACAGCACCCAGCAACTTTCTGCACAGGTGCTCGTGGTTG               GTGCCTTCGCCAAAAGTCTATGCACATCATGCTGTTTCTACTCTTGGGAT               TTCCAAAAGGACCACAGGATATTGGTCCCATTCTATTCAGTTTCTTTTTG               CACAGTATATGCCTGAATGGCTCTGGGTGTGGGGAGCAAATATTCTCAAC               CGTTCACTACGTAAGGAAGCCTTATGCTGCACAGCC TGA   GTCTGGATGGC                   CACTTGAGAAGTTTTGCCAACTCCTGGGAACCTCGATATTCTGACATTTG                   GA                    
 
       [0286] The sequence of NOV10b was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0287] The cDNA coding for the NOV10b sequence was cloned by the polymerase chain reaction (PCR). Primers were designed based on in silico predictions of the full length or some portion (one or more exons) of the cDNA/protein sequence of the invention, or by translated homology of the predicted exons to closely related human sequences or to sequences from other species. The DNA sequence and protein sequence for a novel transmembrane-like gene were obtained by exon linking and are reported here as NOV10b. These primers and methods used to amplify NOV10b cDNA are described in Example 2.  
       [0288] The NOV10b polypeptide (SEQ ID NO: 34) encoded by SEQ ID NO: 33 is 330 amino acid residues in length and is presented using the one-letter amino acid code in Table 10D. The SignalP, Psort and/or Hydropathy results predict that NOV10b has no known signal peptide and is likely to be localized at the plasma membrane with a certainty of 0.7000. In alternative embodiments, a NOV10b polypeptide is located to the mitochondrial inner membrane with a certainty of 0.6577, the microbody (peroxisome) with a certainty of 0.4320, or the mitochondrial matrix space with a certainty of 0.2792.  
               TABLE 10D                       Encoded NOV10b Protein Sequence                                        (SEQ ID NO:34)                         MAAVDSFYLLYREIARSCNCYMEALALVGAWYTARKSITVICDFYSLIRL                   HFIPRLGSRADLIKQYGRWAVVSGATDGIGKAYAEELASRGLNIILISRN               EEKLQVVAKDIADTYKVETDIIVADFSSGREIYLPIREALKDKDVGILVN               NVGVFYPYPQYFTQLSEDKLWDIINVNIAAASLMVHVVLPGMVERKKGAI               VTISSGSCCKPTPQLAAFSASKAYLDHFSRALQYEYASKGIFVQSLIPFY               VATSMTAPSNFLHRCSWLVPSPKVYAHHAVSTLGISKRTTGYWSHSIQFL               FAQYMPEWLWVWGANILNRSLRKEALCCTA                  
 
       [0289] SNP variants of NOV10 are disclosed in Example 3.  
       [0290] NOV10 Clones  
       [0291] Unless specifically addressed as NOV10a or NOV10b, any reference to NOV10 is assumed to encompass all variants.  
       [0292] The amino acid sequence of NOV10 has high homolgy to other proteins as shown in Table 10E.  
               TABLE 10E                          BLASTX Results from Patp Database for NOV10                                 Smallest           High   Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P (N)                                     patp: AAM39603   Human polypeptide   1715   2.2e−176       patp: AAM41389   Human polypeptide   1715   2.2e−176       patp: AAM93392   Human polypeptide   1710   7.4e−176       patp: AAU18335   Human endocrine polypeptide   1449   3.4e−148       patp: AAM42370   Human polypeptide   1264   1.4e−128                  
 
       [0293] In a search of sequence databases, it was found, for example, that the NOV10a nucleic acid sequence of this invention has 859 of 899 bases (95%) identical to a gb:GENBANK-ID:AK025626|acc:AK025626.1 mRNA from  Homo sapiens  ( Homo sapiens  cDNA: FLJ21973 fis, clone HEP05846). Further, the fill amino acid sequence of the disclosed NOV10a protein of the invention has 123 of 302 amino acid residues (40%) identical to, and 188 of 302 amino acid residues (62%) similar to, the 312 amino acid residue ptnr:SPTREMBL-ACC:Q9Y6G8 protein from  Homo sapiens  (Human) (STEROID DEHYDROGENASE HOMOLOG).  
       [0294] In a similar search of sequence databases, it was found, for example, that the NOV10b nucleic acid sequence of this invention has 350 of 351 bases (99%) identical to a gb:GENBANK-ID:AK025626|acc:AK025626.1 mRNA from  Homo sapiens  ( Homo sapiens  cDNA: FLJ21973 fis, clone HEP05846). Further, the full amino acid sequence of the disclosed protein of the invention has 122 of 299 amino acid residues (40%) identical to, and 187 of 299 amino acid residues (62%) similar to, the 312 amino acid residue ptnr:SPTREMBL-ACC:Q9Y6G8 protein from  Homo sapiens  (Human) (STEROID DEHYDROGENASE HOMOLOG).  
       [0295] Additional BLASTP results are shown in Table 10F.  
               TABLE 10F                          NOV10 BLASTP Results                                     Gene Index/       Length of           Expect       Identifier   Protein/Organism   aa   Identity (%)   Positives (%)   Value               Q9BY22   STEROID   309   309/309   309/309    2.6e−164           DEHYDROGENASE-LIKE       (100%)   (100%)           PROTEIN -  Homo sapiens             (Human)       Q9VJG9   CG13284 PROTEIN -   339   125/310   191/310   9.5e−57             Drosophila melanogaster         (40%)   (61%)           (Fruit fly)       Q9Y6G8   STEROID   312   123/302   188/302   2.5e−56           DEHYDROGENASE       (40%)   (62%)           HOMOLOG -             Homo sapiens  (Human)       O57314   Putative steroid   312   121/228   163/238   5.3e−56           dehydrogenase SPM2 (EC       (50%)   (68%)           1.1.1.-) -             Anas platyrhynchos             (Domestic duck)       O70503   Putative steroid   312   122/281   180/281   3.7e−55           dehydrogenase KIK-I (EC       (43%)   (64%)           1.1.1.-) -  Mus musculus             (Mouse)                  
 
       [0296] A multiple sequence alignment is given in Table 10G, with the NOV10 protein of the invention being shown in lines 1 and 2, in a ClustalW analysis comparing NOV10 with related protien sequences of Table 10F. 
 
 
 
       [0297] Domain results for NOV10 were collected from the Pfam database, and then identified by the Interpro domain accession number. The results are listed in Table 10H with the statistics and domain description. These results indicate that the NOV10 polypeptides have properties similar to those of other proteins known to contain these domains.  
               TABLE 10H                          Domain Analysis of NOV10                                 Score   E           PSSMs Producing Significant Alignments   (bits)   Value               Short Chain Alcohol Dehydrogenase (adh_short): domain 1 of 1,   95.6   9.8e-25           from 66 to 306                                     ADH Short   tgKvaLvTGassGIGlaiAkrLakeGakVvvvdrreekaegvaaelk   (SEQ ID NO:102)                ++++++ |++  |||+++|++|+++|  +++++ +++++++  +++ ++       NOV10a   YGRWAVVSGATDGIGKAYAEELASRGLNIILISRNEEKLQVVAKDIA   (SEQ ID NO:32)               NOV10a   aelGdralfiqlDvtdeeqvkaavaqaverlGd.rlDvLVNNAGilgpgp             + ++   +++| ++  +    +  +++++ ++  + +||||+|+  + +       NOV10a   DTYKVETDIIVADFSSGRE---IYLPIREALKDkDVGILVNNVGVFYPYP                   pfe.elseedwervidvNltGvflltqavlpamdhmlkrkgGrIvNisSv              + ++++    +++++|+ ++ +++  +++    + ++++| |+ ++|       NOV10a   QYFtQLSEDKLWDIINVNIAAASLMVHVVLP---GMVERKKGAIVTTSSG                   aGlnvgvpglsaYsASKaavigltrsLAlElaphgtgIrVnavaPGgvdT           ++  ++ +++++  +|||+ + +++++|+ |++ ++  | | +   |  +++|       NOV10a   SCC-KPTPQLAAFSASKAYLDHFSRALQYEYASKG--IFVQSLIPFYVAT                   dmtkalrsrlieakkkvrevadiadpeleerits.titplgrygv.tpee           ++++ ++                      + + ++ ++ +    + + +       NOV10a   SMTAPSN---------------------FLHRCSwLV-PSPKVYAhHAVS                   ianavlfLasdgasysvtgqtlnvdggl             ++    +  ++       + ++++ +       NOV10a   TLGISKRTTGYWSHS---IQFLFAQYMP                  
 
       [0298] The NOV10 proteins disclosed in this invention is expressed in at least the following tissues: adrenal gland/suprarenal gland, bone, bone marrow, brain—whole, brain—hippocampus, brain—hypothalamus, dermis, epidermis, hair follicles, lymph node, t-cell, eye, ovary and testis. This information was derived by determining the tissue sources of the sequences that were included in the invention including but not limited to SeqCalling sources, Public EST sources, Literature sources, and/or RACE sources.  
       [0299] The protein similarity information, expression pattern, and map location for the steroid dehydrogenase-like protein and nucleic acid disclosed herein suggest that this protein may have important structural and/or physiological functions characteristic of the steroid dehydrogenase family. Therefore, the nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, the compositions of the present invention will have efficacy for treatment of patients suffering from: 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, adrenoleukodystrophy, congenital adrenal hyperplasia, neoplasia, diabetes, digestion, Von Hippel-Lindau (VHL) syndrome, cirrhosis, pancreatitis, endometriosis, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, autoimmume disease, allergies, immunodeficiencies, transplantation, graft versus host disease, osteoporosis, hypercalceimia, arthritis, ankylosing spondylitis, scoliosis, muscular dystrophy, Lesch-Nyhan syndrome, myasthenia gravis, Alzheimer&#39;s disease, stroke, tuberous sclerosis, hypercalceimia, 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, psoriasis, actinic keratosis, acne, hair growth/loss, allopecia, pigmentation disorders, endocrine disorders, and other diseases, disorders and conditions of the like.  
       [0300] The novel nucleic acid encoding the steroid dehydrogenase-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV10 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV10 epitope is from about amino acids 10 to 15. In another embodiment, a contemplated NOV10 epitope is from about amino acids 50 to 70. In other specific embodiments, contemplated NOV10 epitopes are from about amino acids 75 to 80, 80 to 85, 85 to 95, 100 to 110, 120 to 125, 125 to 140, 155 to 175, 200 to 205, 210 to 215, 215 to 225, 225 to 240, 260 to 275, 275 to 300, and 310 to 325.  
       [0301] NOV11  
       [0302] Yet a further NOVX protein of the invention, referred to herein as NOV11 (alternatively referred to as CG50311-01), is a myosin heavy chain-like protein.  
       [0303] Myosins are molecular motors that upon interaction with actin filaments convert energy from ATP hydrolysis into mechanical force. Myosins can be divided into at least three main classes, with two types of unconventional myosin being no more related to each other than they are to conventional myosin. Myosins have traditionally been classified as conventional or unconventional, with many of the unconventional myosin proteins thought to be distributed in a narrow range of organisms. Members of all three of these main classes are likely to be present in most or all eukaryotes.  
       [0304] Although SignalP, Psort and/or hydropathy suggest that the myosin heavy chain-like protein may be localized in the nucleus, the NOVI I protein predicted here is similar to the myosin heavy chain family, some members of which are expected to have intracellular sub-cellular localization. Therefore it is likely that this novel myosin heavy chain-like protein is available at the same sub-cellular localization and hence accessible to a diagnostic probe and for various therapeutic applications.  
       [0305] The NOV11 protein disclosed in this invention maps to chromosome 22. This information was assigned using OMIM, the electronic northern bioinformatic tool implemented by CuraGen Corporation, public ESTs, public literature references and/or genomic clone homologies.  
       [0306] The NOV11 nucleic acid (SEQ ID NO: 35) of 7396 nucleotides encodes a novel myosin heavy chain-like protein and is shown in Table 11A. An open reading frame for the mature protein was identified beginning with a ATG initiation codon at nucleotides 140-142 and ending with a TAA codon at nucleotides 6017-6019. Putative untranslated regions upstream from the start codon and downstream from the termination codon are underlined in Table 11A. The start and stop codons are in bold letters.  
               TABLE 11A                       NOV11 Nucleotide Sequence                                              CAAGGCTGACCTGCTGCAGCTCCCGCCTCGTGCGCTCGCCCCACCCGGCCGCCGCCCGAGCGCTCGAGAAAGTC     (SEQ ID NO:35)                     CTCTCGGGAGAAGCAGCGCCTGTTCCCGGGGCAGATCCAGGTTCAGGTCCTGGCTATAAGTCACC   ATG GCACAG               CAAGCTGCCGATAAGTATCTCTATGTGGATAAAAACTTCATCAACAATCCGCTGGCCCAGGCCGACTGGGCTGC               CAAGAAGCTGGTATGGGTGCCTTCCGACAAGAGTGGCTTTGAGCCAGCCAGCCTCAAGGAGGAGGTGGGCGAAG               AGGCCATCGTGGAGCTGGTGGAGAATGGGAAGAAGGTGAAGGTGAACAAGGATGACATCCAGAAGATGAACCCG               CCCAAGTTCTCCAAGGTGGAGGACATGGCAGAGCTCACGTGCCTCAACGAAGCCTCGGTGCTGCACAACCTCAA               GGAGCGTTACTACTCAGGGCTCATCTACACCTATTCAGGCCTGTTCTGTGTGGTCATCAATCCTTACAAGAACC               TGCCCATCTACTCTGAAGAGATTGTGGAAATGTACAAGGGCAAGAAGAGGCACGAGATGCCCCCTCACATCTAT               GCCATCACAGACACCGCCTACAGGAGTATGATGCAAGACCGAGAAGATCAATCCATCTTGTGCACTGGTGAATC               TGGAGCTGGCAAGACGGAGAACACCAAGAAGGTCATCCAGTATCTGGCGTACGTGGCGTCCTCGCACAAGAGCA               AGAAGGACCAGGGCGAGCTGGAGCGGCAGCTGCTGCAGGCCAACCCCATCCTGGAGGCCTTCGGGAACGCCAAG               ACCGTGAAGAATGACAACTCCTCCCGCTTCGGCAAATTCATTCGCATCAACTTTGATGTCAATGGCTACATTGT               TGGAGCCAACATTGAGACTTATCTTTTGGAGAAATCTCGTGCTATCCGCCAAGCCAAGGAAGAACGGACCTTCC               ACATCTTCTATTATCTCCTGTCTGGGGCTGGAGAGCACCTGAAGACCGATCTCCTGTTGGAGCCGTACAACAAA               TACCGCTTCCTGTCCAATGGACACGTCACCATCCCCGGGCAGCAGGACAAGGACATGTTCCAGGAGACCATGGA               GGCCATGAGGATTATGGGCATCCCAGAAGAGGAGCAAATGGGCCTGCTGCGGGTCATCTCAGGGGTTCTTCAGC               TCGGCAACATCGTCTTCAAGAAGGAGCGGAACACTGACCAGGCGTCCATGCCCGACAACACAGCTGCCCAAAAG               GTGTCCCATCTCTTGGGTATCAATGTGACCGATTTCACCAGAGGAATCCTCACCCCGCGCATCAAGGTGGGACG               GGATTACGTCCAGAAGGCGCAGACTAAAGAGCAGGCTGACTTTGCCATCGAGGCCTTGGCCAAGGCGACCTATG               AGCGGATGTTCCGCTGGCTGGTGCTGCGCATCAACAAGGCTCTGGACAAGACCAAGAGGCAGGGCGCCTCCTTC               ATCGGGATCCTGGACATTGCCGGCTTCGAGATCTTTGATCTGAACTCGTTTGAGCAGCTGTGCATCAATTACAC               CAATGAGAAGCTGCAGCAGCTCTTCAACCACACCATGTTCATCCTGGAGCAGGAGGAGTACCAGCGCGAGGGCA               TCGAGTGGAACTTCATCGACTTTGGCCTCGACCTGCAGCCCTGCATCGACCTCATTGAGAAGCCAGCAGGCCCC               CCGGGCATTCTGGCCCTGCTGGACGAGGAGTGCTGGTTCCCCAAAGCCACCGACAAGAGCTTCGTGGAGAAGGT               GATGCAGGAGCAGGGCACCCACCCCAAGTTCCAGAAGCCCAAGCAGCTGAAGGACAAAGCTGATTTCTGCATTA               TCCACTATGCCGGCAAGGTGGATTACAAAGCTGACGAGTGGCTGATGAAGAACATGGATCCCCTGAATGACAAC               ATCGCCACACTGCTCCACCAGTCCTCTGACAAGTTTGTCTCGGAGCTGTGGAAGGATGTGGACCGCATCATCGG               CCTGGACCAGGTGGCCGGCATGTCGGAGACCGCACTGCCCGGGGCCTTCAAGACGCGGAAGGGCATGTTCCGCA               CTGTGGGGCAGCTTTACAAGGAGCAGCTGGCCAAGCTGATGGCTACGCTGAGGAACACGAACCCCAACTTTGTC               CGCTGCATCATCCCCAACCACGAGAAGAAGGCCGGCAAGCTGGACCCGCATCTCGTGCTGGACCAGCTGCGCTG               CAACGGTGTTCTCGAGGGCATCCGTATCTGCCGCCAGGGCTTCCCCAACAGGGTGGTCTTCCAGGAGTTTCGGC               AGAGATATGAGATCCTGACTCCAAACTCCATTCCCAAGGGTTTCATGGACGGGAAGCAGGCGTGCGTGCTCATG               ATAAAAGCCCTGGAGCTCGACAGCAATCTGTACCGCATTGGCCAGAGCAAAGTCTTCTTCCGTGCCGGTGTGCT               GGCCCACCTGGAGGAGGAGCGAGACCTGAAGATCACCGACGTCATCATAGGGTTCCAGGCCTGCTGCAGGGGCT               ACCTGGCCAGGAAAGCATTTGCCAAGCGGCAGCAGCAGCTTACCGCCATGAAGGTCCTCCAGCGGAACTGCGCT               GCCTACCTGAAGCTGCGGAACTGGCAGTGGTGGCGGCTCTTCACCAAGGTCAAGCCGCTGCTGCAGGTGAGCCG               GCAGGAGGAGGAGATGATGGCCAAGGAGGAGGAGCTGGTGAAGGTCAGAGAGAAGCAGCTGGCTGCGGAGAACA               GGCTCATGGAGATGGAGACGCTGCAGTCTCAGCTCATGGCAGAGAAATTGCAGCTGCAGGAGCAGCTCCAGGCA               GAAACCGAGCTGTGTGCCGAGGCTGAGGAGCTCCGGGCCCGCCTGACCGCCAAGAAGCAGGAATTAGAAGAGAT               CTGCCATGACCTAGAGGCCAGGGTGGAGGAGGAGGAGGAGCGCTACCAGCACCTGCAGGCGGAGAAGAAGAAGA               TGCAGCAGAACATCCAGGAGCTTGAGGAGCAGCTGGAGGAGGAGGAGAGCGCCCGGCAGAAGCTGCAGCTGGAG               AAGGTGACCACCGAGGCGAAGCTGAAAAAGCTGGAGGAGGAGCAGATCATCCTGGAGGACCAGAACTGCAAGCT               GGCCAAGGAAAAGAAACTGCTGGAAGACAGAATAGCTGAGTTCACCACCAACCTCACAGAAGAGGAGGAGAAAT               CTAAGAGCCTCGCCAAGCTCAAGAACAAGCATGAGGCAATGATCACTGACTTGGAAGAGCGCCTCCGCAGGGAG               GAGAAGCAGCGACAGGAGCTGGAGAAGACCCGCCGGAAGCTGGAGGGAGACTCCACAGACCTCAGCGACCAGAT               CGCCGAGCTCCAGGCCCAGATCGCGGAGCTCAAGATGCAGCTGGCCAAGAAAGAGGAGGAGCTCCAGGCCGCCC               TGGCCAGAGTGGAAGAGGAAGCTGCCCAGAAGAACATGGCCCTCAAGAAGATCCGGGAGCTGGAATCTCAGATC               TCTGAACTCCAGGAAGACCTGGAGTCTGAGCGTGCTTCCAGGAATAAAGCTGAGAAGCAGAAACGGGACCTTGG               GGAAGAGCTAGAGGCGCTGAAAACAGAGTTGGAGGACACGCTGGATTCCACAGCTGCCCAGCAGGAGCTCAGGT               CAAAACGTGAGCAGGAGGTGAACATCCTGAAGAAGACCCTGGAGGAGGAGGCCAAGACCCACGAGGCCCAGATC               CAGGAGATGAGGCAGAAGCACTCACAGGCCGTGGAGGAGCTGGCGGAGCAGCTGGAGCAGACGAAGCGGGTGAA               AGCAAACCTCGAGAAGGCAAAGCAGACTCTGGAGAACGAGCGGGGGGAGCTGGCCAACGAGGTGAAGGTGCTGC               TGCAGGGCGGAAGGGACTCGGAGCACAAGCGCAAGAAAGTGGAGGCGCAGCTGCAGGAGCTGCAGGTCAAGTTC               AACGAGGGAGAGCGGGTGCGCACAGAGCTGGCCGACAAGGTCACCAAGCTGCAGGTGGAGCTGGACAACGTGAC               CGGGCTTCTCAGCCAGTCCGACAGCAAGTCCAGCAAGCTCACCAAGGACTTCTCCGCGCTGGAGTCCCAGCTGC               AGGACACTCAGGAGCTGCTGCAGGAGGAGAACCGGCAGAAGCTGAGCCTGAGCACCAAGCTCAAGCAGGTGGAG               GACGAGAAGAATTCCTTCCGGGAGCAGCTGGAGGAGGAGGAGGCCAAGCACAACCTGGAGAAGCAGATCGCCAC               CCTCCATGCCCAGGTGGCCGACATGAAAAAGAAGATGGAGGACAGTGTGGGGTGCCTGGAAACTGCTGAGGAGG               TGAAGAGGAAGCTCCAGAAGGACCTGGAGGGCCTGAGCCAGCGGCACGAGGAGAAGGTGGCCGCCTACGACAAG               CTGGAGAAGACCAAGACGCGGCTGCAGGAGGAGCTGGACGACCTGCTGGTGGACCTGGACCACCAGCGCCAGAG               CGCGTGCAACCTGGAGAAGAAGCAGAAGAAGTTTGACCAGCTCCTGGCGGAGGAGAAGACCATCTCTGCCAAGT               ATGCAGAGGAGCGCGACCGGGCTGAGGCGGAGGCCCGAGAGAAGGAGACCAAGGCTCTGTCGCTGGCCCGGGCC               CTGGAGGAAGCCATGGAGCAGAAGGCGGAGCTGGAGCGGCTCAACAAGCAGTTCCGCACGGAGATGGAGGACCT               TATGAGCTCCAAGGATGATGTGGGCAAGAGTGTCCACGAGCTGGAGAAGTCCAAGCGGGCCCTAGAGCAGCAGG               TGGAGGAGATGAAGACGCAGCTGGAAGAGCTGGAGGACGAGCTGCAGGCCACCGAAGATGCCAAGCTGCGGTTG               GAGGTCAACCTGCAGGCCATGAAGGCCCAGTTCGAGCGGGACCTGCAGGGCCGGGACGAGCAGAGCGAGGAGAA               GAAGAAGCAGCTGGTCAGACAGGTGCGGGAGATGGAGGCAGAGCTGGAGGACGAGAGGAAGCAGCGCTCGATGG               CAGTGGCGGCGCGGAAGAAGCTGGAGATGGACCTGAAGGACCTGGAGGCGCACATCGACTCGGCCAACAAGAAC               CGGGACGAAGCCATCAAACAGCTGCGGAAGCTGCAGGCCCAGATGAAGGACTGCATGCGCGAGCTGGATGACAC               CCGCGCCTCTCGTGAGGAGATCCTGGCCCAGGCCAAAGAGAACGAGAAGAAGCTGAAGAGCATGGAGGCCGAGA               TGATCCAGTTGCAGGAGGAACTGGCAGCCGCGGAGCGTGCCAAGCGCCAGGCCCAGCAGGAGCGGGATGAGCTG               GCTGACGAGATCGCCAACAGCAGCGGCAAAGGAGCCCTGGCGTTAGAGGAGAAGCGGCGTCTGGAGGCCCGCAT               CGCCCAGCTGGAGGAGGAGCTGGAGGAGGAGCAGGGCAACACGGAGCTGATCAACGACCGGCTGAAGAAGGCCA               ACCTGCAGATCGACCAGATCAACGCCGACCTGAACCTGGAGCGCGGGCACGCCCAGAAGAACGAGAATGCTCGG               CAGCAGCTGGAACGCCAGAACAAGGAGCTTAAGGTCAAGCTGCAGGAGATGGAGGGCACTGTCAAGTCCAAGTA               CAAGGCCTCCATCACCGCCCTCGAGGCCAAGATTGCACAGCTGGAGGAGCAGCTGGACAACGAGACCAAGGAGC               GCCAGGCAGCCTGCAAACAGGTGCGTCGGACCGAGAAGAAGCTGAAGGATGTGCTGCTGCAGGTGGATGACGAG               CGGAGGAACGCCGAGCAGTACAAGGACCAGGCCGACAAGGCATCTACCCGCCTGAAGCAGCTCAAGCGGCAGCT               GGAGGAGGCCGAAGAGGAGGCCCAGCGGGCCAACGCCTCCCGCCGGAAACTGCAGCGCGAGCTGGAGGACGCCA               CTGAGACGGCCGATGCCATGAACCGCGAAGTCAGCTCCCTAAAGAACAAGCTCAGGCGCGGGGACCTGCCGTTT               GTCGTGCCCCGCCGAATGGCCCGGAAAGGCGCCGGGGATGGCTCCGACGAAGAGGTAGATGGCAAAGCGGATGG               GGCTGAGGCCAAACCTGCCGAA TAA   GCCTCTTCTCCTGCAGCCTGAGATGGATGGACAGACAGACACCACAGCC                   TCCCCTTCCCAGACCCCGCAGCACGCCTCTCCCCACCTTCTTGGGACTGCTGTGAACATGCCTCCTCCTGCCCT                   CCGCCCCGTCCCCCCATCCCGTTTCCCTCCAGGTGTTGTTGAGGGCATTTGGCTTCCTCTGCTGCATCCCCTTC                   CAGCTCCCTCCCCTGCTCAGAATCTGATACCAAAGAGACAGGGCCCGGGCCAGGCAGAGAGCGACCAGCAGGCT                   CCTCAGCCCTCTCTTGCCAAAAAGCACAAGATGTTGAGGCGAGCAGGGCAGGCCCCCGGGGAGGGCAGAGTTTT                   CTATGAATCTATTTTTCTTCAGACTGAGGCCTTTTGGTAGTCGGAGCTCCCCCAGTCGTCAGCCTCCCTGACGT                   CTGCCACCAGCGCCCCCCACTCCTCCTCCTTTCTTTGCTGTTTGCAATCACACGTGGTGACCTCACACACCTCT                   GCCCCTTGGGCCTCCCACTCCATGGCTCTGGGCGGTCAGAAGGAGCAGGCCTGGGCTCCACCTCTGTGCAGGGC                   ACAGAAGGCTGGGGTGGGGGGAGGAGTGGATTCCTCCTACCTGTCCCAGCAGCGCCACTGTCGCTGTCTCCTCT                   GATTCTAAAATGTCTCAAGTGCAATGCCCCCTCCCCTCCTTTACCGAGGACAGCCTGCCTCTGCCACAGCAAGG                   CTGTCGGGGTCAAGCTGGAAAGGCCAGCAGCCTTCCAGTGGCTTCTCCCGAACACTCTTGGGGACCAAATATAC                   TTAATGGTTAAGGGACTTGTCCCAAGTCTGACAGCCAGAGCGTTAGAGGGGCCAGCGGCTCCCCAGGCGATCTT                   GTGTCTACTCTAGGACTGGGCCCGAGGGTGGTTTACCTGCACCGTTGACTCAGTATAGTTTAAAAATCTGCCAC                   CTGCACAGGTATTTTTGAAAGCAAAATAAGGTTTTCTTTTTTCCCCTTTCTTGTAATAAATGATAAAATTCCGA                   GTCTTTCTCACTGCCTTTGTTTAGAAGAGAGTACTCGTCCTCACTGGTCTACACTGGTTGCCGAATTTACTTGT                   ATTCCTAACTGTTTTGTATATGCTGCATTGAGACTTACGGGCAAGAAGGGCATTTTTTTTTTTTAAAGGAAACA                   AACTCTCAAATCATGAAGTGATATAAAAGCTGCATATGCCTACAAAGCTCTGAATTCAGGTCCCAGTTGCTGTC                   ACAAAGGAGTGAGTGAAAACACCCACCCTACCCCCTTTTTTATATAATAAAAGTGCCTTAGCATGTGTTGCAGC                   TGTCACCACTACAGTAAGCTGGTTTACAGATGTTTTCCACTGAGCATCACAATAAAGAGAACCATGTGCT                    
 
       [0307] The sequence of NOV11 was derived by laboratory cloning of cDNA fragments covering the full length and/or part of the DNA sequence of the invention, and/or by in silico prediction of the full length and/or part of the DNA sequence of the invention from public human sequence databases.  
       [0308] The cDNA coding for the NOV11 sequence was cloned by the polymerase chain reaction (PCR). PCR primers were designed based on in silico predictions of the full length or some portion (one or more exons) of the cDNA/protein sequence of the invention. The DNA sequence and protein sequence for a novel myosin heavy chain-like gene were obtained by exon linking, or SeqCalling™ Technology and are reported here as NOV11. These primers and methods used to amplify NOV11 cDNA are described in Example 2.  
       [0309] The NOV11 polypeptide (SEQ ID NO: 36) encoded by SEQ ID NO: 35 is 1959 amino acid residues in length and is presented using the one-letter amino acid code in Table 11B. The SignalP, Psort and/or Hydropathy results predict that NOV11 has no known signal peptide and is likely to be localized at the nucleus with a certainty of 0.9600. In alternative embodiments, a NOV11 polypeptide is located to the microbody (peroxisome) with a certainty of 0.3000, the mitochondrial matrix space with a certainty of 0.1000, or the lysosome (lumen) with a certainty of 0.1000.  
               TABLE 11B                       Encoded NOV11 Protein Sequence                                            MAQQAADKYLYVDKNFINNPLAQADWAAKKLVWVPSDKSGFEPASLKEEVGEEAIVELVENGKKVKVNKDDIQKM   (SEQ ID NO:36)                   NPPKFSKVEDMAELTCLNEASVLHNLKERYYSGLIYTYSGLFCVVINPYKNLPIYSEEIVEMYKGKKRHEMPPHI               YAITDTAYRSMMQDREDQSILCTGESGAGKTENTKKVIQYLAYVASSHKSKKDQGELERQLLQANPILEAFGNAK               TVKNDNSSRFGKFIRINFDVNGYIVGANIETYLLEKSRAIRQAKEERTFHIFYYLLSGAGEHLKTDLLLEPYNKY               RFLSNGHVTIPGQQDKDMFQETMEAMRIMGIPEEEQMGLLRVISGVLQLGNIVFKKERNTDQASMPDNTAAQKVS               HLLGINVTDFTRGILTPRIKVGRDYVQKAQTKEQADFAIEALAKATYERMFRWLVLRINKALDKTKRQGASFIGI               LDIAGFEIFDLNSFEQLCINYTNEKLQQLFNHTMFILEQEEYQREGIEWNFIDFGLDLQPCIDLIEKPAGPPGIL               ALLDEECWFPKATDKSFVEKVMQEQGTHPKFQKPKQLKDKADFCIIHYAGKVDYKADEWLMKNMDPLNDNIATLL               HQSSDKFVSELWKDVDRIIGLDQVAGMSETALPGAFKTRKGMFRTVGQLYKEQLAKLMATLRNTNPNFVRCIIPN               HEKKAGKLDPHLVLDQLRCNGVLEGIRICRQGFPNRVVFQEFRQRYEILTPNSIPKGFMDGKQACVLMIKALELD               SNLYRIGQSKVFFRAGVLAHLEEERDLKITDVIIGFQACCRGYLARKAFAKRQQQLTAMKVLQRNCAAYLKLRNW               QWWRLFTKVKPLLQVSRQEEEMMAKEEELVKVREKQLAAENRLMEMETLQSQLMAEKLQLQEQLQAETELCAEAE               ELRARLTAKKQELEEICHDLEARVEEEEERYQHLQAEKKKMQQNIQELEEQLEEEESARQKLQLEKVTTEAKLKK               LEEEQIILEDQNCKLAKEKKLLEDRIAEFTTNLTEEEEKSKSLAKLKNKHEAMITDLEERLRREEKQRQELEKTR               RKLEGDSTDLSDQIAELQAQIAELKMQLAKKEEELQAALARVEEEAAQKNMALKKIRELESQISELQEDLESERA               SRNKAEKQKRDLGEELEALKTELEDTLDSTAAQQELRSKREQEVNILKKTLEEEAKTHEAQIQEMRQKHSQAVEE               LAEQLEQTKRVKANLEKAKQTLENERGELANEVKVLLQGGRDSEHKRKKVEAQLQELQVKFNEGERVRTELADKV               TKLQVELDNVTGLLSQSDSKSSKLTKDFSALESQLQDTQELLQEENRQKLSLSTKLKQVEDEKNSFREQLEEEEA               KHNLEKQIATLHAQVADMKKKMEDSVGCLETAEEVKRKLQKDLEGLSQRHEEKVAAYDKLEKTKTRLQQELDDLL               VDLDHQRQSACNLEKKQKKFDQLLAEEKTISAKYAEERDRAEAEAREKETKALSLARALEEAMEQKAELERLNKQ               FRTEMEDLMSSKDDVGKSVHELEKSKRALEQQVEEMKTQLEELEDELQATEDAKLRLEVNLQAMKAQFERDLQGR               DEQSEEKKKQLVRQVREMEAELEDERKQRSMAVAARKKLEMDLKDLEAHIDSANKNRDEAIKQLRKLQAQMKDCM               RELDDTRASREEILAQAKENEKKLKSMEAEMIQLQEELAAAERAKRQAQQERDELADEIANSSGKGALALEEKRR               LEARIAQLEEELEEEQGNTELINDRLKKANLQIDQINADLNLERGHAQKNENARQQLERQNKELKVKLQEMEGTV               KSKYKASITALEAKIAQLEEQLDNETKERQAACKQVRRTEKKLKDVLLQVDDERRNAEQYKDQADKASTRLKQLK               RQLEEAEEEAQRANASRRKLQRELEDATETADAMNREVSSLKNKLRRGDLPFVVPRRMARKGAGDGSDEEVDGKA               DGAEAKPAE                  
 
       [0310] SNP variants of NOV11 are disclosed in Example 3.  
       [0311] The amino acid sequence of NOV11 has high homology to other proteins as shown in Table 11C.  
               TABLE 11C                          BLASTX Results from Patp Database for NOV11                                 Smallest           High   Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P (N)                                     patp: AAM78854   Human protein   9773   0.0       patp: AAM79838   Human protein   9760   0.0       patp: AAM40999   Human polypeptide   7760   0.0       patp: AAM41000   Human polypeptide   7760   0.0       patp: AAW00024   Smooth muscle myosin heavy   7619   0.0           chain SM1 isoform protein -             Mus musculus                    
 
       [0312] In a search of sequence databases, it was found, for example, that the NOV11 nucleic acid sequence of this invention has 5116 of 5122 bases (99%) identical to a gb:GENBANK-ID:HUMMYONM|acc:M31013.1 mRNA from Homo sapiens (Human nonmuscle myosin heavy chain (NMHC) mRNA, 3′ end). Further, the fill amino acid sequence of the disclosed protein of the invention was found to have 1953 of 1960 amino acid residues (99%) identical to, and 1953 of 1960 amino acid residues (99%) similar to, the 1960 amino acid residue ptnr:SWISSPROT-ACC:P35579 protein from Homo sapiens (Human) (MYOSIN HEAVY CHAIN, NONMUSCLE TYPE A (CELLULAR MYOSIN HEAVY CHAIN, TYPE A) (NMMHC-A)).  
       [0313] Additional BLASTP results are shown in Table 11D.  
               TABLE 11D                          NOV11 BLASTP Results                                     Gene Index/       Length of           Expect       Identifier   Protein/Organism   aa   Identity (%)   Positives (%)   Value               A61231   myosin heavy chain   1961   1955/1961   1956/1961   0.0           nonmuscle form A - human       (99%)   (99%)       P35579   Myosin heavy chain,   1960   1953/1960   1953/1960   0.0           nonmuscle type A (Cellular       (99%)   (99%)           myosin heavy chain, type           A) (Nonmuscle myosin           heavy chain-A) (NMMHC-           A) -  Homo sapiens  (Human)       Q62812   Myosin heavy chain,   1961   1879/1961   1916/1961   0.0           nonmuscle type A (Cellular       (95%)   (97%)           myosin heavy chain, type           A) (Nonmuscle myosin           heavy chain-A) (NMMHC-           A) -  Rattus norvegicus  (Rat)       P14105   Myosin heavy chain,   1959   1813/1959   1892/1959   0.0           nonmuscle (Cellular myosin       (92%)   (96%)           heavychain) (NMMHC) -              Gallus gallus  (Chicken)       Q63731   NEURONAL MYOSIN   1999   1781/1951   1838/1951   0.0           HEAVY CHAIN -  Rattus         (91%)   (94%)             norvegicus  (Rat)                  
 
       [0314] A multiple sequence alignment is given in Table 11E in a ClustalW analysis comparing NOV11 with related protein sequences disclosed in Table 11D. 
 
 
 
 
 
 
       [0315] Domain results for NOV11were collected from the Pfam database, and then identified by the Interpro domain accession number. The results are listed in Table 11F with the statistics and domain description. These results indicate that the NOV11 polypeptide has properties similar to those of other proteins known to contain these domains.  
               TABLE 11F                          Domain Analysis of NOV11                                 Score   E           PSSMs Producing Significant Alignments   (bits)   Value               myosin_head (Motor domain): domain 1 of 1, from 83 to 764   1494.5   0.0                                     Myosin Head   vEDmveLtyLnEpsvlhNLKkRyksdlIYTYsGlvLvsvNPYkrLpq   (SEQ ID NO:108)           +||+++|++|+| +++++|||+|| ++++||||+|++++++|||++|+       NOV11   VEDMAELTCLNEASVLHNLKERYYSGLIYTYSGLFCVVINPYKNLP-   (SEQ ID NO:36)                   iYteeiiakYrGKrryElPPHiFAiADeAYRsMlsdkeNQsilISGESGA           +|+++++++ |+||+++|+|||++|+ | |||+|  +++++|+++++|||||       NOV11   IYSEEIVEMYKGKKRHEMPPHIYAITDTAYRSMMQDREDQSILCTGESGA                   GKTEntKkvmqYlAaVsggnsgngeevpsvkvgrvEdqILqsNpiLEAFG           ||||++| ++++|+|+|+++++++      +   +++| ++|++||+|||||       NOV11   GKTENTKKVIQYLAYVASSHKSK------KDQGELERQLLQANPILEAFG                   NAKTtRNNNSSRFGKyieIqFdktGkivGakIenYLLEKSRVvyQtegER           ||||++|+|||||||+++ |+|+ +|+|||++|++ |||||||+++|+++||       NOV11   NAKTVKNDNSSRFGKFIRINFDVNGYIVGANIETYLLEKSRAIRQAKEER                   NFHIFYQLLaGasqqnlkkeLkLtndpedYhYLnqggevkpcytvdGiDD           +|||||+||+|+ +  ++  +|+|+   ++|++|++++      ++++| +|       NOV11   TFHIFYYLLSGAGEH-LKTDLLLE-PYNKYRFLSNGH-----VTIPGQQD                   segnveeFketrkAmdilGftdeeqrsIFrivAaILhlGNikFkqrrkee           +     +|+++  +|++++|+ ++++++ +++++++|++||+  |+++++  +       NOV11   K----DMFQETMEAMRIMGIPEEEQMGLLRVISGVLQLGNIVFKKERNTD                   aaipddnnadtkalekaaeLlGvdatelekALlsrriktGtegrkStvtk           +++++++     ++++++++|+|+++++++++++++++++ |+++     +++       NOV11   QASMPDN----TAAQKVSHLLGINVTDFTRGILTPRIKVGRDY----VQK                   pqnveQAsyARDALAKalYsRLFdWIVnrINktLdfkakegqdasfIGVL           +++++|| + |++||||+ |+|+| |+| +||++|+++++++   +++||+|       NOV11   AQTKEQADFAIEALAKATYERMFRWLVLRINKALDKTKRQG--ASFIGIL                   DIyGFEIFekNSFEQLCINYvNEKLQQfFNhhmFklEQEEYkrEGIeWtf           ||+|||||+ ||||||||||+||||||+||+++|++||||| ++|||+|++       NOV11   DIAGFEIFDLNSFEQLCINYTNEKLQQLFNHTMFILEQEEYQREGIEWNF                   IdFgdNLQpcIDLIEkKs.PpGILsLLDEeClfPkaqSGtDqtFldKLys           |+|+++||++|||||++  +|+|||+||||+|++|++    +|++|++|+ +       NOV11   IDFGLDLQPCIDLIEKPAgPPGILALLDEECWFPKA---TDKSFVEKVMQ                   tfskhpahfekfsPrfrqkksgahFiikHYAGdVeYnvegFleKNKDpLf           +   ++  +++    ++++ ++++ |++ ||||+|+| ++  +++||+|+|+       NOV11   EQGTHP-KFQ----KPKQLKDKADFCIIHYAGVKDYKADEWLMKNMDPLN                   ddlisllksSsnpllaeLFpdeetlagpfeadpsslskkrksgskNkstg           +++  ++  +|+++++ +|+++ +++ + ++  ++ +++     +       NOV11   DNIATLLHQSSDKFVSELWKDVDRIIGLDQVAGMSETALPGAF-------                   kktkksnfiTvGaqfKeslneLMktLsstnLPHFvRCIkPNekKkagvfD            ++++++++|+|+++|+++++||++|++++  |+|+|||+||++|+++++ |       NOV11   -KTRKGMFRTVGQLYKEQLAKLMATLRNTN-PNFVRCIIPNHEKKAGKLD                   aslVlhQLrclGVLEgiRIrRaGFPnRitfdeFlqRYriLapktwPkwsg            ++|++||+++ ||||++||+|+|||+|+ +++|++||++|+++  +|++++       NOV11   PHLVLDQLRCNGVLEGIRICRQGFPNPVVFQEFRQRYEILTPNSIPKGFM                   dakkgeknEIvaceklLqsLnlDkgeeyrfGkTKIFFR           ++++        ++ +++++|++|+ + +++ |++|+|||       NOV11   DGKQ-------ACVLMIKALELDS-NLYRIGQSKVFFR                  
 
       [0316] The myosin heavy chain-like protein disclosed in this invention is expressed in at least the following tissues: 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, Bone, Cervix, Chorionic Villus, Cochlea, Cornea, Coronary Artery, Dermis, Epidermis, Foreskin, Hair Follicles, Hypothalamus, Kidney Cortex, Liver, Lung, Lymph node, Lymphoid tissue, Oesophagus, Ovary, Parathyroid Gland, Peripheral Blood, Tonsils, Umbilical Vein, Whole Organism. This information was derived by determining the tissue sources of the sequences that were included in the invention including but not limited to SeqCalling sources, Public EST sources, Literature sources, and/or RACE sources.  
       [0317] The protein similarity information, expression pattern, and map location for the myosin heavy chain-like protein and nucleic acid disclosed herein suggest that this protein may have important structural and/or physiological functions characteristic of the nonmuscle myosins family. Therefore, the NOV11 nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, the compositions of the present invention may have efficacy for treatment of patients suffering from: restenosis, neurological, glomerular diseases and other diseases, disorders and conditions of the like.  
       [0318] The novel nucleic acid encoding the myosin heavy chain-like protein of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV11 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV11 epitope is from about amino acids 1 to 150. In another embodiment, a contemplated NOV11 epitope is from about amino acids 150 to 225. In other specific embodiments, contemplated NOV11 epitopes are from about amino acids 300 through 1950.  
       [0319] NOV12  
       [0320] Another NOVX protein of the invention, referred to herein as NOV12, includes three novel pancreatitis-associated protein (PAP)-like protein. The disclosed proteins have been named NOV12a, NOV12b, and NOV12c.  
       [0321] PAP is synthesized as a preprotein with a molecular weight of 16.6 kDa. A search of protein databases reveals marked homolgy with the carbohydrate binding region of animal lectins. Although PAP has no hemagglutination activity, it does induce extensive bacterial aggregation. Further, the pattern of expression for PAP reveals that it is not found in the liver, stomach, salivary glands, brain, kidney, or testis. Such an expression pattern correlates to a stress protein involved in the control of bacterial proliferation.  
       [0322] At least the NOV12a protein disclosed herein is predicted to localize extracellularly. Therefore, it is likely that this protein is accessible to a diagnostic probe, and for the various therapeutic applications described herein.  
       [0323] NOV12a  
       [0324] In one embodiment, a NOV12 variant is NOV12a (alternatively referred to herein as CG50323-01), which encodes a novel pancreatitis-associated protein (PAP)-like protein and includes the 530 nucleotide sequence (SEQ ID NO: 37) shown in Table 12A. An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 3-5 and ending with a TAA codon at nucleotides 528-530. Putative untranslated regions downstream from the termination codon and upstream from the initiation codon are underlined in Table 12A, and the start and stop codons are in bold letters.  
                   TABLE 12A                       NOV12a Nucleotide Sequence                                        (SEQ ID NO:37)                           CC   ATG GCCCTGCCAAGTGTATCTTGGATGCTGCTTTCCTGCCTCATGCTG                   CTGTCTCAGGTTCAAGGTGAAGAACCCCAGAGGGAACTGCCCTCTGCACG               GATCCGCTGTCCCAAAGGCTCCAAGGCCTATGGCTCCCACTGCTATGCCT               TGTTTTTGTCACCAAAATCCTGGACAGATGCAGATCTGGCCTGCCAGAAG               CGGCCCTCTGGAAACCTGGTGTCTGTGCTCAGTGGGGCTGAGGGATCCTT               CGTGTCCTCCCTGGTGAAGAGCATTGGTAACAGCTACTCATACGTCTGGA               TTGGGCTCCATGACCCCACACAGGGCACCGAGCCCAATGGAGAAGGTTGG               GAGTGGAGTAGCAGTGATGTGATGAATTACTTTGCATGGGAGAGAAATCC               CTCCACCATCTCAAGCCCCGGCCACTGTGCGAGCCTGTCGAGAAGCACAG               CATTTCTGAGGTGGAAAGATTATAACTGTAATGTGAGGTTACCCTATGTC               TGCAAGTTCAAATACTGGAGGCAATTG TAA                    
 
       [0325] The sequence of NOV12a was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. The cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
       [0326] The cDNA coding for the NOV12a sequence was cloned by the polymerase chain reaction (PCR). PCR primers were designed based on in silico predictions of the full length or some portion (one or more exons) of the cDNA/protein sequence of the invention. The DNA sequence and protein sequence for a novel PAP-like gene were obtained by exon linking, or SeqCalling™ Technology and are reported here as NOV12a. These primers and methods used to amplify NOV12a cDNA are described in Example 2.  
       [0327] The NOV12a polypeptide (SEQ ID NO: 38) encoded by SEQ ID NO: 37 is 175 amino acid residues in length and is presented using the one-letter amino acid code in Table 12B. The SignalP, Psort and/or Hydropathy results predict that NOV12a has a signal peptide and is likely to be localized extracellularly with a certainty of 0.4896. In alternative embodiments, a NOV12a polypeptide is located to the microbody (peroxisome) with a certainty of 0.1669, the endoplasmic reticulum (membrane) with a certainty of 0.1000, or the endoplasmic reticulum (lumen) with a certainty of 0.1000.  
               TABLE 12B                       Encoded NOV12a Protein Sequence                                        (SEQ ID NO:38)                         MALPSVSWMLLSCLMLLSQVQGEEPQRELPSARIRCPKGSKAYGSHCYAL                   FLSPKSWTDADLACQKRPSGNLVSVLSGAEGSFVSSLVKSIGNSYSYVWI               GLHDPTQGTEPNGEGWEWSSSDVMNYFAWERNPSTISSPGHCASLSRSTA               FLRWKDYNCNVRLPYVCKFKYWRQL                  
 
       [0328] NOV12b -NOV12c  
       [0329] In alternative embodiments, a NOV12 variant is NOV12b or NOV12c (alternatively referred to herein as 169475472 and 169475476, respectively), which include a 471 nucleotide sequence. NOV12b and NOV12c are insert assemblies that encode an open reading frame of NOV12a between residues 23 and 173. Table 12C notes the minor nucleotide and amino acid changes in NOV12b and NOV12c from the parent clone, NOV12a.  
                                           Nov   Alternate   Change in DNA   Change in Protein Seq.       No.   Reference   Seq. from NOV12a   from NOV12a                  12b   169475472   A → G at bp 395   No change       12c   169475476   T → C at bp 479   No change                  
 
       [0330] The sequences of NOV12b and NOV12c were derived by laboratory cloning of cDNA fragments coding for a domain of the full length form of CG50323-01 (NOV12a), between residues 23 to 173. The cDNA coding for the NOV12b and NOV12c sequences was cloned by the polymerase chain reaction (PCR). The PCR template is the previoisly identified plasma (NOV12a), when available, or human cDNA. These primers and methods used to amplify NOV12b and NOV12c cDNA are described in Example 2.  
       [0331] SNP variants of NOV12 are disclosed in Example 3.  
       [0332] NOV12 Clones  
       [0333] Unless specifically addressed as NOV12a, NOV12b, or NOV12c, any reference to NOV12 is assumed to encompass all variants.  
       [0334] The amino acid sequence of NOV12 has high homolgy to other proteins as shown in Table 12D.  
               TABLE 12D                          BLASTX Results from Patp Database for NOV12                                 Smallest           High   Sum       Sequences Producing High-Scoring Segment Pairs:   Score   Prob P (N)                                     patp: AAR54098   Mouse PAP   921   3.0e−92       patp: AAR57117   Human Pancreatitis-Associated Protein   921   3.0e−92       patp: AAB43568   Human cancer associated protein   921   3.0e−92       patp: AAR14795   Fragment A3 from human pancreatitis associated protein   915   1.3e−91       patp: AAW71682   Human pancreatitis-associated protein   813   8.4e−81                  
 
       [0335] In a search of sequence databases, it was found, for example, that the NOV12a nucleic acid sequence of the invention has 514 of 520 bases (98%) identical to a gb:GENBANK-ID:S51768|acc:S51768.1 mRNA from Homo sapiens (PAP-H=pancreatitis-associated protein [human, pancreas, mRNA, 797 nt]). Further, the full amino acid sequence of the disclosed protein of the invention has 169 of 169 amino acid residues (100%) identical to, and 169 of 169 amino acid residues (100%) similar to, the 175 amino acid residue ptnr:SWISSPROT-ACC:Q06141 protein from Homo sapiens (Human) (PANCREATITIS-ASSOCIATED PROTEIN 1 PRECURSOR).  
       [0336] Additional BLASTP results are shown in Table 12E.  
               TABLE 12E                          NOV12 BLASTP Results                                     Gene Index/       Length of                   Identifier   Protein/Organism   aa   Identity (%)   Positives (%)   Expect Value               Q06141   Pancreatitis-associated   175   169/169   169/169   3.8e−92           protein 1 precursor -  Homo         (100%)   (100%)             sapiens  (Human)       P23132   Lithostathine precursor   175   118/169   144/169   2.8e−66           (Pancreatic stone protein)       (69%)    (85%)            (PSP) (Pancreatic thread           protein) (PTP) (Islet of           langerhans regenerating           protein) (REG) (Islet cells           regeneration factor)           (ICRF) -  Bos taurus             (Bovine)       P25031   Pancreatitis-associated   175   117/169   140/169   1.9e−65           protein 1 precursor (Peptide       (69%)    (82%)            23) (REG-2) -  Rattus               norvegicus  (Rat)       P35230   Pancreatitis-associated   175   115/164   135/164   2.2e−64           protein 1 precursor (REG       (70%)    (82%)            III-beta) -  Mus musculus             (Mouse)       P42854   Pancreatitis-associated   174   117/170   141/170   5.3e−63           protein 3 precursor -  Rattus         (68%)    (82%)              norvegicus  (Rat)                  
 
       [0337] A multiple sequence alignment is given in Table 12F, with the NOV12 protein of the invention being shown in lines 1, 2, and 3, in a ClustalW analysis comparing NOV12 with related protien sequences of Table 12E. 
 
 
       [0338] Domain results for NOV12 were collected from the Pfam database, and then identified by the Interpro domain accession number. The results are listed in Table 12G with the statistics and domain description. These results indicate that the NOV12 polypeptides have properties similar to those of other proteins known to contain these domains.  
               TABLE 12G                       Domain Analysis of NOV12                                                    Score   E           PSSMSs Producing Significant Alignments   (bits)   Value               lectin_c type domain: domain 1 of 1, from 53 to 169   146.5   4.5e−40                                     Lectin-C   esktWaeAelaCqkegghAHLvsIqsaeEqsfvvafltsltkksnty   (SEQ ID NO:114)               ++++|++|+++|++++++ +|+++ + +| ++++++++++ + ++++       NOV12a   SPKSWTDADLACQKRPSG-NLVSVLSGAEGSFVSSLVKSIGN-SYSY   (SEQ ID NO:38)                   aWIGLtdintegtwvwegwetdgspvnytenWapgePnnrgnhGgnEdCv           +||||+++++  ++++++++++ +++++++ | +++++        ++|+       NOV12a   VWIGLHDPTQGTEPNGEGWEWSSSDVMNYFAWERNPSTISS----PGHCA                   eiytdtdflaGkWnDepCdsklpyvCef           +++++++++  +|+| +|++ ++++|++       NOV12a   SLSRSTAFL-RWKDYNCNVRLPYVCKF                  
 
       [0339] The NOV12 proteins disclosed in this invention are expressed in at least the following tissues: at very low expression level in healthy pancreas and at much higher level during the acute phase of pancreatitis; it is also expressed at high level in normal small intestine. This information was derived by determining the tissue sources of the sequences that were included in the invention including but not limited to SeqCalling sources, Public EST sources, Literature sources, and/or RACE sources.  
       [0340] The protein similarity information, expression pattern, and map location for the PAP-like protein and nucleic acid disclosed herein suggest that this protein may have important structural and/or physiological functions characteristic of the Lectin C family. Therefore, the NOV12 nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. For example, the compositions of the present invention will have efficacy for treatment of patients suffering from: acute pancreatitis and chronic pancreatitis, and other diseases, disorders and conditions of the like.  
       [0341] The novel NOV12 proteins of the invention, or fragments thereof, are useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. These materials are further useful in the generation of antibodies that bind immunospecifically to the novel substances of the invention for use in therapeutic or diagnostic methods. These 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 NOV12 protein has multiple hydrophilic regions, each of which can be used as an immunogen. In one embodiment, a contemplated NOV12 epitope is from about amino acids 20 to 45. In another embodiment, a contemplated NOV12 epitope is from about amino acids 45 to 57. In other specific embodiments, contemplated NOV12 epitopes are from about amino acids 55 to 70, 72 to 77, 95 to 143, and 145 to 170.  
       [0342] NOVX Nucleic Acids and Polypeptides  
       [0343] 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.  
       [0344] 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.  
       [0345] 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.  
       [0346] The term “isolated” nucleic acid molecule, as utilized herein, is one, which is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5′- and 3′-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.). Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material or culture medium when produced by recombinant techniques, or of chemical precursors or other chemicals when chemically synthesized.  
       [0347] A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 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.  
       [0348] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.  
       [0349] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 is one that is sufficiently complementary to the nucleotide sequence shown SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27,29, 31, 33, 35, and 37 that it can hydrogen bond with little or no mismatches to the nucleotide sequence shown SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 thereby forming a stable duplex.  
       [0350] 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.  
       [0351] 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.  
       [0352] 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.  
       [0353] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.  
       [0354] 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 bona fide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.  
       [0355] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37; or an anti-sense strand nucleotide sequence of SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37; or of a naturally occurring mutant of SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37.  
       [0356] 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.  
       [0357] “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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, 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.  
       [0358] NOVX Nucleic Acid and Polypeptide Variants  
       [0359] The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences shown in SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37. 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 NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38.  
       [0360] In addition to the human NOVX nucleotide sequences shown in SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, 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.  
       [0361] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from the human SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 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.  
       [0362] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37. 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.  
       [0363] 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.  
       [0364] 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.  
       [0365] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, 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).  
       [0366] In a second embodiment, a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, 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, NY, and Kriegler, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY.  
       [0367] In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, 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% formrnamide, 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, NY, and Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY; Shilo and Weinberg, 1981.  Proc Natl Acad Sci USA  78: 6789-6792.  
       [0368] Conservative Mutations  
       [0369] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, 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 NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38. 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.  
       [0370] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 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 NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38. Preferably, the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38; more preferably at least about 70% homologous SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38; still more preferably at least about 80% homologous to SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38; even more preferably at least about 90% homologous to SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38; and most preferably at least about 95% homologous to SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38.  
       [0371] An isolated nucleic acid molecule encoding an NOVX protein homologous to the protein of SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38 can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.  
       [0372] Mutations can be introduced into SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 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 SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.  
       [0373] 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, VLIM, HFY, wherein the letters within each group represent the single letter amino acid code.  
       [0374] 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).  
       [0375] 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).  
       [0376] Antisense Nucleic Acids  
       [0377] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35,and 37, 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 NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 29, and 31, or antisense nucleic acids complementary to an NOVX nucleic acid sequence of SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, are additionally provided.  
       [0378] 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).  
       [0379] 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).  
       [0380] 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-metbylguanine, 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).  
       [0381] 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 (erg., 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.  
       [0382] 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).  
       [0383] Ribozymes and PNA Moieties  
       [0384] 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.  
       [0385] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37). 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.  
       [0386] 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.  
       [0387] 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.  
       [0388] 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).  
       [0389] 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.  
       [0390] In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al., 1989.  Proc. Natl. Acad. Sci. U.S.A.  86: 6553-6556; Lemaitre, et al., 1987.  Proc. Natl. Acad. Sci.  84: 648-652; PCT Publication No. WO88/098 10) 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.  
       [0391] NOVX Polypeptides  
       [0392] A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38 while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.  
       [0393] 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.  
       [0394] 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.  
       [0395] 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.  
       [0396] 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.  
       [0397] 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 NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38) 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.  
       [0398] 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.  
       [0399] In an embodiment, the NOVX protein has an amino acid sequence shown SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38, and retains the functional activity of the protein of SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38, 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 NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38, and retains the functional activity of the NOVX proteins of SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38.  
       [0400] Determining Homology Between Two or More Sequences  
       [0401] 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”).  
       [0402] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37. 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.  
       [0403] Chimeric and Fusion Proteins  
       [0404] 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 NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, and 38, 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.  
       [0405] 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.  
       [0406] 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.  
       [0407] 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.  
       [0408] 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.  
       [0409] NOVX Agonists and Antagonists  
       [0410] 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.  
       [0411] 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.  
       [0412] Polypeptide Libraries  
       [0413] 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 SI 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.  
       [0414] 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.  
       [0415] Anti-NOVX Antibodies  
       [0416] 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.  
       [0417] 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.  
       [0418] 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. Nat. 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.  
       [0419] 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.  
       [0420] 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.  
       [0421] Polyclonal Antibodies  
       [0422] 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).  
       [0423] 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).  
       [0424] Monoclonal Antibodies  
       [0425] 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.  
       [0426] 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.  
       [0427] 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.  
       [0428] 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).  
       [0429] 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.  
       [0430] 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.  
       [0431] 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.  
       [0432] 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.  
       [0433] Humanized Antibodies  
       [0434] 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)).  
       [0435] Human Antibodies  
       [0436] 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).  
       [0437] 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)).  
       [0438] 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.  
       [0439] 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.  
       [0440] 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.  
       [0441] 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.  
       [0442] F ab  Fragments and Single Chain Antibodies  
       [0443] 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.  
       [0444] Bispecific Antibodies  
       [0445] 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.  
       [0446] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello,  Nature,  305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published May, 13, 1993, and in Traunecker et al., 1991  EMBO J.,  10:3655-3659.  
       [0447] 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).  
       [0448] 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.  
       [0449] 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.  
       [0450] 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.  
       [0451] 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).  
       [0452] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al.,  J. Immunol.  147:60 (1991).  
       [0453] 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).  
       [0454] Heteroconjugate Antibodies  
       [0455] 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.  
       [0456] Effector Function Engineering  
       [0457] 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).  
       [0458] Immunoconjugates  
       [0459] 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).  
       [0460] 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.  
       [0461] 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.  
       [0462] 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.  
       [0463] 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.  
       [0464] 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”).  
       [0465] 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.  
       [0466] NOVX Recombinant Expression Vectors and Host Cells  
       [0467] 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.  
       [0468] 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).  
       [0469] 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.).  
       [0470] 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.  
       [0471] 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.  
       [0472] Examples of suitable inducible non-fusion  E. coli  expression vectors include pTrc (Amrann et al., (1988)  Gene  69:301-315) and pET 11d (Studier et al., GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).  
       [0473] 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.  
       [0474] 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.).  
       [0475] 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).  
       [0476] 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.  
       [0477] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987.  Genes Dev.  1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988.  Adv. Immunol.  43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989.  EMBO J.  8: 729-733) and immunoglobulins (Banerji, et al., 1983.  Cell  33: 729-740; Queen and Baltimore, 1983.  Cell  33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989.  Proc. Natl. Acad. Sci. USA  86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985.  Science  230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990.  Science  249: 374-379) and the ¤-fetoprotein promoter (Campes and Tilghman, 1989.  Genes Dev.  3: 537-546).  
       [0478] The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively-linked to a regulatory sequence in a manner that allows for expression (by transcription of the DNA molecule) of an RNA molecule that is antisense to NOVX mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen that direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen that direct constitutive, tissue specific or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see, e.g., Weintraub, et al., “Antisense RNA as a molecular tool for genetic analysis,”  Reviews - Trends in Genetics , Vol. 1(1) 1986.  
       [0479] 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.  
       [0480] 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.  
       [0481] 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.  
       [0482] 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).  
       [0483] 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.  
       [0484] Transgenic NOVX Animals  
       [0485] 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.  
       [0486] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 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.  
       [0487] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37), 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 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).  
       [0488] 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.  
       [0489] 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.  
       [0490] In another embodiment, transgenic non-humans animals can be produced that contain selected systems that allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage P1. For a description of the cre/loxP recombinase system, See, e.g., Lakso, et al., 1992.  Proc. Natl. Acad. Sci. USA  89: 6232-6236. Another example of a recombinase system is the FLP recombinase system of  Saccharomyces cerevisiae . See, O&#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.  
       [0491] 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.  
       [0492] Pharmaceutical Compositions  
       [0493] 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.  
       [0494] 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.  
       [0495] 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.  
       [0496] 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.  
       [0497] 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.  
       [0498] 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.  
       [0499] 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.  
       [0500] 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.  
       [0501] 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.  
       [0502] 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.  
       [0503] 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.  
       [0504] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.  
       [0505] Screening and Detection Methods  
       [0506] 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.  
       [0507] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.  
       [0508] Screening Assays  
       [0509] 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.  
       [0510] 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.  
       [0511] 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.  
       [0512] 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. USA.  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.  
       [0513] 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.).  
       [0514] 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.  
       [0515] 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.  
       [0516] 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.  
       [0517] 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.  
       [0518] 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.  
       [0519] 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.  
       [0520] The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesit®, Isotridecypoly(ethylene glyco 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).  
       [0521] 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.  
       [0522] 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.  
       [0523] 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.  
       [0524] 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.  
       [0525] 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.  
       [0526] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.  
       [0527] Detection Assays  
       [0528] 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.  
       [0529] Chromosome Mapping  
       [0530] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, 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.  
       [0531] 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.  
       [0532] 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.  
       [0533] 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.  
       [0534] 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).  
       [0535] 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.  
       [0536] 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.  
       [0537] 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.  
       [0538] Tissue Typing  
       [0539] 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).  
       [0540] 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.  
       [0541] 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).  
       [0542] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37 are used, a more appropriate number of primers for positive individual identification would be 500-2,000.  
       [0543] Predictive Medicine  
       [0544] 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.  
       [0545] 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.)  
       [0546] 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.  
       [0547] These and other agents are described in further detail in the following sections.  
       [0548] Diagnostic Assays  
       [0549] 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 NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37, or a port 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.  
       [0550] 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.  
       [0551] 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.  
       [0552] 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.  
       [0553] 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.  
       [0554] Prognostic Assays  
       [0555] 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.  
       [0556] 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).  
       [0557] 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.  
       [0558] 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.  
       [0559] 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.  
       [0560] 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.  
       [0561] 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.  
       [0562] 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).  
       [0563] 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.  
       [0564] 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.  
       [0565] 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.  
       [0566] 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.  
       [0567] 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.  
       [0568] 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.  
       [0569] 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.  
       [0570] 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.  
       [0571] Pharmacogenomics  
       [0572] 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.  
       [0573] 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.  
       [0574] 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.  
       [0575] 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.  
       [0576] Monitoring of Effects During Clinical Trials  
       [0577] 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.  
       [0578] 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.  
       [0579] 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.  
       [0580] Methods of Treatment  
       [0581] 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, immnunodeficiencies, 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.  
       [0582] These methods of treatment will be discussed more fully, below.  
       [0583] Disease and Disorders  
       [0584] 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.  
       [0585] 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.  
       [0586] 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).  
       [0587] Prophylactic Methods  
       [0588] 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.  
       [0589] Therapeutic Methods  
       [0590] 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.  
       [0591] 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).  
       [0592] Determination of the Biological Effect of the Therapeutic  
       [0593] 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.  
       [0594] 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.  
       [0595] Prophylactic and Therapeutic Uses of the Compositions of the Invention  
       [0596] 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.  
       [0597] 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.  
       [0598] 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.  
       [0599] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. 
     
    
    
     EXAMPLES  
     Example 1  
     [0600] Quantitative Expression Analysis of Clones in Various Cells and Tissues  
     [0601] The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoimmune diseases), Panel CNSD.01 (containing central nervous system samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer&#39;s diseased brains).  
     [0602] 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.  
     [0603] 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.  
     [0604] 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.  
     [0605] 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.  
     [0606] 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.  
     [0607] 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. minute. Results were analyzed and processed as described previously.  
     [0608] Panels 1, 1.1, 1.2, and 1.3D  
     [0609] 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.  
     [0610] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:  
     [0611] ca.=carcinoma,  
     [0612] *=established from metastasis,  
     [0613] met=metastasis,  
     [0614] s cell var=small cell variant,  
     [0615] non-s=non-sm=non-small,  
     [0616] squam=squamous,  
     [0617] pl. eff pl=effusion=pleural effusion,  
     [0618] glio=glioma,  
     [0619] astro=astrocytoma, and  
     [0620] neuro=neuroblastoma.  
     [0621] General_screening_panel_v1.4  
     [0622] The plates for Panel 1.4 include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panel 1.4 are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in Panel 1.4 are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on Panel 1.4 are comprised of pools of samples derived from all major organ systems from 2 to 5 different adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose. Abbreviations are as described for Panels 1, 1. 1, 1.2, and 1.3D.  
     [0623] Panels 2D and 2.2  
     [0624] The plates for Panels 2D and 2.2 generally include 2 control wells and 94 test samples composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute&#39;s Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI). The tissues are derived from human malignancies and in cases where indicated many malignant tissues have “matched margins” obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted “NAT” in the results below. The tumor tissue and the “matched margins” are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI or CHTN). This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, Calif.), Research Genetics, and Invitrogen.  
     [0625] Panel 3D  
     [0626] 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.  
     [0627] Panels 4D, 4R, and 4.1D  
     [0628] 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.).  
     [0629] 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.  
     [0630] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10-5M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10-5M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2×106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10-5M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.  
     [0631] 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 5.5×10-5M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10-5M (Gibco), 10 mM Hepes (Gibco) and 10% AB Human Serum or MCSF at approximately 50 ng/ml. Monocytes, macrophages and dendritic cells were stimulated for 6 and 12-14 hours with lipopolysaccharide (LPS) at 100 ng/ml. Dendritic cells were also stimulated with anti-CD40 monoclonal antibody (Pharmingen) at 10 μg/ml for 6 and 12-14 hours.  
     [0632] 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 5.5×10-5M (Gibco), and 10 mM Hepes (Gibco) and plated at 106 cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0.5 μg/ml anti-CD28 (Pharmingen) and 3 ug/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the cells were harvested for RNA preparation. To prepare chronically activated CD8 lymphocytes, we activated the isolated CD8 lymphocytes for 4 days on anti-CD28 and anti-CD3 coated plates and then harvested the cells and expanded them in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10-5M (Gibco), and 10 mM Hepes (Gibco) and IL-2. The expanded CD8 cells were then activated again with plate bound anti-CD3 and anti-CD28 for 4 days and expanded as before. RNA was isolated 6 and 24 hours after the second activation and after 4 days of the second expansion culture. The isolated NK cells were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10-5M (Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.  
     [0633] To obtain B cells, tonsils were procured from NDRI. The tonsil was cut up with sterile dissecting scissors and then passed through a sieve. Tonsil cells were then spun down and resupended at 106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10-5M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24,48 and 72 hours.  
     [0634] To prepare the primary and secondary Th1/Th2 and Tr1 cells, six-well Falcon plates were coated overnight with 10 μg/ml anti-CD28 (Pharmingen) and 2 μg/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic Systems, German Town, Md.) were cultured at 105-106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10-5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4 ng/ml). IL-12 (5ng/ml) and anti-IL4 (1 μg/ml) were used to direct to Th1, while IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct to Tr1. After 4-5 days, the activated Th1, Th2 and Tr1 lymphocytes were washed once in DMEM and expanded for 4-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10-5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (1 ng/ml). Following this, the activated Th1, Th2 and Tr1 lymphocytes were re-stimulated for 5 days with anti-CD28/OKT3 and cytokines as described above, but with the addition of anti-CD95L (1 μg/ml) to prevent apoptosis. After 4-5 days, the Th1, Th2 and Tr1 lymphocytes were washed and then expanded again with IL-2 for 4-7 days. Activated Th1 and Th2 lymphocytes were maintained in this way for a maximum of three cycles. RNA was prepared from primary and secondary Th1, Th2 and Tr1 after 6 and 24 hours following the second and third activations with plate bound anti-CD3 and anti-CD28 mAbs and 4 days into the second and third expansion cultures in Interleukin 2.  
     [0635] The following leukocyte cells lines were obtained from the ATCC: Ramos, EOL-1, KU-812. EOL cells were further differentiated by culture in 0.1 mM dbcAMP at 5×105 cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×105 cells/ml. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10-5M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10-5M (Gibco), and 10 mM Hepes (Gibco). CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.  
     [0636] For these cell lines and blood cells, RNA was prepared by lysing approximately 107 cells/ml using Trizol (Gibco BRL). Briefly, {fraction (1/10)} volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 5 μl DTT, 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with {fraction (1/10)} volume of 3M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at −80° C.  
     [0637] AI_Comprehensive Panel_v1.0  
     [0638] The plates for AI_comprehensive panel_v1.0 include two control wells and 89 test samples comprised of cDNA isolated from surgical and postmortem human tissues obtained from the Backus Hospital and Clinomics (Frederick, Md.). Total RNA was extracted from tissue samples from the Backus Hospital in the Facility at CuraGen. Total RNA from other tissues was obtained from Clinomics.  
     [0639] 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.  
     [0640] 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.  
     [0641] 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.  
     [0642] Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD was purchased from Clinomics. Emphysema patients ranged in age from 40-70 and all were smokers, this age range was chosen to focus on patients with cigarette-linked emphysema and to avoid those patients with alpha-1 anti-trypsin deficiencies. Asthma patients ranged in age from 36-75, and excluded smokers to prevent those patients that could also have COPD. COPD patients ranged in age from 35-80 and included both smokers and non-smokers. Most patients were taking corticosteroids, and bronchodilators.  
     [0643] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:  
     [0644] AI=Autoimmunity  
     [0645] Syn=Synovial  
     [0646] Normal=No apparent disease  
     [0647] Rep22 /Rep20=individual patients  
     [0648] RA=Rheumatoid arthritis  
     [0649] Backus=From Backus Hospital  
     [0650] OA=Osteoarthritis  
     [0651] (SS) (BA) (MF)=Individual patients  
     [0652] Adj=Adjacent tissue  
     [0653] Match control=adjacent tissues  
     [0654] -M=Male  
     [0655] -F=Female  
     [0656] COPD =Chronic obstructive pulmonary disease  
     [0657] Panels 5D and 5I  
     [0658] 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.  
     [0659] 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.  
     [0660] Patient 2: Diabetic Hispanic, overweight, not on insulin  
     [0661] Patient 7-9: Nondiabetic Caucasian and obese (BMI&gt;30)  
     [0662] Patient 10: Diabetic Hispanic, overweight, on insulin  
     [0663] Patient 11: Nondiabetic African American and overweight  
     [0664] Patient 12: Diabetic Hispanic on insulin  
     [0665] Adipocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr. 2, 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:  
     [0666] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose  
     [0667] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated  
     [0668] Donor 2 and 3 AD: Adipose, Adipose Differentiated  
     [0669] 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.  
     [0670] 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.  
     [0671] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:  
     [0672] GO Adipose=Greater Omentum Adipose  
     [0673] SK=Skeletal Muscle  
     [0674] UT=Uterus  
     [0675] PL=Placenta  
     [0676] AD=Adipose Differentiated  
     [0677] AM=Adipose Midway Differentiated  
     [0678] U=Undifferentiated Stem Cells  
     [0679] Panel CNSD.01  
     [0680] 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.  
     [0681] 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.  
     [0682] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:  
     [0683] PSP=Progressive supranuclear palsy  
     [0684] Sub Nigra=Substantia nigra  
     [0685] Glob Palladus=Globus palladus  
     [0686] Temp Pole=Temporal pole  
     [0687] Cing Gyr=Cingulate gyrus  
     [0688] BA 4=Brodman Area 4  
     [0689] Panel CNS_Neurodegeneration_V1.0  
     [0690] 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.  
     [0691] 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.  
     [0692] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:  
     [0693] AD=Alzheimer&#39;s disease brain; patient was demented and showed AD-like pathology upon autopsy  
     [0694] Control=Control brains; patient not demented, showing no neuropathology  
     [0695] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology  
     [0696] SupTemporal Ctx=Superior Temporal Cortex  
     [0697] Inf Temporal Ctx=Inferior Temporal Cortex  
     [0698] NOV1a and NOV1b (AC084364.5/cg-AC084364.5 and 11400078/CG50736-10: Stabilin_Like)  
     [0699] Expression of gene AC084364.5 and variant CG50736-10 was assessed using the primer-probe sets Ag03, Ag068, Ag812, Ag2742, Ag2743, Ag2744, Ag2745 and Ag2746, described in Tables AA, AB, AC, AD, AE, AF, AG, AH and AI. Results of the RTQ-PCR runs are shown in Tables AJ, AK, AL, AM and AN.  
                   TABLE AA                          Probe Name Ag03                                                 Start           Primers   Sequences   Length   Position                                         Forward   5′-ctggttgtaggttgccatggt-3′ (SEQ ID NO:115)   21   7156                   Probe   TET-5′-cagcttcgttggcacaggcctctc-3′-TAMRA (SEQ ID   24   7130           NO:116)               Reverse   5′-ccagtataagctgacctttgacaaag-3′ (SEQ ID NO:117)   26   7101                  
 
     [0700]                   TABLE AB                          Probe Name Ag068                                                 Start           Primers   Sequences   Length   Position                                         Forward   5′-ctggttgtaggttgccatggt-3′ (SEQ ID NO:118)   21   7156                   Probe   TET-5′-cagcttcgttggcacaggcctctc-3′-TAMRA (SEQ ID   24   7130           NO:119)               Reverse   5′-ccagtataagctgacctttgacaaag-3′ (SEQ ID NO:120)   26   7101                    
     [0701]                   TABLE AC                          Probe Name Ag793                                                 Start           Primers   Sequences   Length   Position                                         Forward   5′-ccaaggttttagctgtggatct-3′ (SEQ ID NO:121)   22   5936                   Probe   TET-5′-acatccactgcctggaagaccctg-3′-TAMRA (SEQ ID   24   5962           NO:122)               Reverse   5′-cacatttcacactcagctctga-3′ (SEQ ID NO:123)   22   5992                    
     [0702]                   TABLE AD                          Probe Name Ag812                                                 Start           Primers   Sequences   Length   Position                                         Forward   5′-caggagcatttcgtgaaaga-3′ (SEQ ID NO:124)   20   5329                   Probe   TET-5′-ttttgcaoctttatctgcagcctttg-3′-TAMRA (SEQ ID   26   5376           NO:125)               Reverse   5′-tttaacccgagcttcctcat-3′ (SEQ ID NO:126)   20   5402                    
     [0703]                   TABLE AE                          Probe Name Ag2742                                                 Start           Primers   Sequences   Length   Position                                         Forward   5′-ctgcaaaatcttacgactttgg-3′ (SEQ ID NO:127)   22   5701                   Probe   TET-5′-caacaaacaatggctacatcaaatttagca-3′-TAMRA (SEQ   30   5723           ID NO:128)               Reverse   5′-atgacactcagcaaacctgagt-3′ (SEQ ID NO:129)   22   5765                    
     [0704]                   TABLE AF                          Probe Name Ag2743                                                 Start           Primers   Sequences   Length   Position                                         Forward   5′-ctgcaaaatcttacgactttgg-3′ (SEQ ID NO:130)   22   5701                   Probe   TET-5═-caacaaacaatggctacatcaaatttagca-3′-TAMRA (SEQ   30   5723           ID NO:131)               Reverse   5′-atgacactcagcaaacctgagt-3′ (SEQ ID NO:132)   22   5765                    
     [0705]                   TABLE AG                          Probe Name Ag2744                                                 Start           Primers   Sequences   Length   Position                                         Forward   5′-ctgcaaaatcttacgactttgg-3′ (SEQ ID NO:133)   22   5701                   Probe   TET-5′-caacaaacaatggctacatcaaatttagca-3′-TAMRA (SEQ   30   5723           ID NO:134)               Reverse   5′-tcagcaaacctgagtcctgta-3′ (SEQ ID NO:135)   21   5759                    
     [0706]                   TABLE AH                          Probe Name Ag2745                                                 Start           Primers   Sequences   Length   Position                                         Forward   5′-ctgcaaaatcttacgactttgg-3′ (SEQ ID NO:136)   22   5701                   Probe   TET-5′-caacaaacaatggctacatcaaatttagca-3′-TAMRA (SEQ   30   5723           ID NO:137)               Reverse   5′-atgacactcagcaaacctgagt-3′ (SEQ ID NO:138)   22   5765                    
     [0707]                   TABLE AI                          Probe Name Ag2746                                                 Start           Primers   Sequences   Length   Position                                         Forward   5′-ctgcaaaatcttacgactttgg-3′ (SEQ ID NO:139)   22   5701                   Probe   TET-5′-caacaaacaatggctacatcaaatttagca-3′-TAMRA (SEQ   30   5723           ID NO:140)               Reverse   5′-atgacactcagcaaacctgagt-3′ (SEQ ID NO:141)   22   5765                    
     [0708]               TABLE AJ                          Panel 1                                         Rel. Exp. (%)   Rel. Exp. (%)       Rel. Exp. (%)   Rel. Exp. (%)           Ag03, Run   Ag068, Run       Ag03, Run   Ag068, Run       Tissue Name   87353672   87361479   Tissue Name   87353672   87361479                                             Endothelial cells   0.0   0.0   Renal ca. 786-0   0.0   0.0       Endothelial cells   0.0   0.0   Renal ca. A498   0.1   0.5       (treated)       Pancreas   0.0   2.3   Renal ca. RXF   0.0   0.0                   393       Pancreatic ca.   0.0   0.0   Renal ca.   0.0   0.0       CAPAN 2           ACHN       Adrenal gland   0.5   1.3   Renal ca. UO-   0.0   0.1                   31       Thyroid   1.8   2.1   Renal ca. TK-10   0.2   0.9       Salivary gland   2.5   3.0   Liver   14.2   12.9       Pituitary gland   0.8   0.8   Liver (fetal)   25.7   15.6       Brain (fetal)   0.1   0.4   Liver ca.   0.0   0.1                   (hepatoblast)                   HepG2       Brain (whole)   0.3   0.6   Lung   0.5   0.1       Brain (amygdala)   0.1   0.4   Lung (fetal)   4.4   6.2       Brain   0.4   0.7   Lung ca. (small   0.0   0.0       (cerebellum)           cell) LX-1       Brain   0.3   0.9   Lung ca. (small   0.1   0.4       (hippocampus)           cell) NCI-H69       Brain (substantia   0.1   0.3   Lung ca. (s.cell   0.0   0.0       nigra)           var.) SHP-77       Brain (thalamus)   0.1   0.2   Lung ca. (large   0.0   0.0                   cell)NCI-H460       Brain   0.4   0.5   Lung ca. (non-   0.0   0.1       (hypothalamus)           sm. cell) A549       Spinal cord   0.0   0.3   Lung ca. (non-   0.0   0.3                   s.cell) NCI-H23       glio/astro U87-   0.0   0.1   Lung ca. (non-   0.0   0.1       MG           s.cell) HOP-62       glio/astro U-118-   0.1   0.2   Lung ca. (non-   0.0   0.0       MG           s.cl) NCI-H522       astrocytoma   0.0   0.0   Lung ca.   0.0   0.1       SW1783           (squam.) SW                   900       neuro*; met SK-   0.0   0.0   Lung ca.   0.1   0.3       N-AS           (squam.) NCI-                   H596       astrocytoma SF-   0.0   0.1   Mammary gland   4.7   5.1       539       astrocytoma SNB-   0.1   0.2   Breast ca.*   0.0   0.2       75           (pl.ef) MCF-7       glioma SNB-19   0.6   1.6   Breast ca.*   0.1   0.4                   (pl.ef) MDA-                   MB-231       glioma U251   0.2   0.9   Breast ca.* (pl.   0.1   0.4                   ef) T47D       glioma SF-295   0.1   0.2   Breast ca. BT-   0.0   0.0                   549       Heart   0.3   0.3   Breast ca.   0.1   0.6                   MDA-N       Skeletal muscle   0.3   0.4   Ovary   3.6   1.3       Bone marrow   3.5   3.0   Ovarian ca.   0.0   0.1                   OVCAR-3       Thymus   0.3   0.2   Ovarian ca.   0.0   0.0                   OVCAR-4       Spleen   100.0   100.0   Ovarian ca.   0.1   0.6                   OVCAR-5       Lymph node   29.3   81.2   Ovarian ca.   0.2   0.7                   OVCAR-8       Colon (ascending)   0.8   1.0   Ovarian ca.   0.0   0.3                   IGROV-1       Stomach   1.2   1.5   Ovarian ca.   0.0   0.2                   (ascites) SK-                   OV-3       Small intestine   1.6   1.7   Uterus   0.2   0.4       Colon ca. SW480   0.0   0.0   Placenta   1.9   1.6       Colon ca.*   0.0   0.1   Prostate   0.7   1.0       SW620 (SW480       met)       Colon ca. HT29   0.0   0.1   Prostate ca.*   0.0   0.0                   (bone met) PC-3       Colon ca. HCT-   0.0   0.0   Testis   23.5   22.1       116       Colon ca. CaCo-2   0.1   0.1   Melanoma   0.0   0.1                   Hs688(A).T       Colon ca. HCT-15   0.1   0.7   Melanoma*   0.0   0.1                   (met)                   Hs688(B).T       Colon ca. HCC-   0.0   0.3   Melanoma   0.0   0.0       2998           UACC-62       Gastric ca. (liver   0.1   0.2   Melanoma M14   0.1   0.5       met) NCI-N87       Bladder   1.1   0.2   Melanoma LOX   0.1   0.5                   IMVI       Trachea   2.4   2.2   Melanoma*   0.0   0.0                   (met) SK-MEL-5       Kidney   0.1   0.4   Melanoma SK-   0.3   1.3                   MEL-28       Kidney (fetal)   1.0   1.3                    
     [0709]               TABLE AK                          Panel 1.2                                         Rel. Exp. (%)   Rel. Exp. (%)       Rel. Exp. (%)   Rel. Exp. (%)           Ag812, Run   Ag812, Run       Ag812, Run   Ag812, Run       Tissue Name   118348259   121953945   Tissue Name   118348259   121953945                                             Endothelial cells   0.0   0.0   Renal ca. 786-0   0.0   0.0       Heart (Fetal)   0.3   5.6   Renal ca. A498   0.3   0.1       Pancreas   2.0   0.6   Renal ca. RXF   0.0   0.0                   393       Pancreatic ca.   0.0   0.0   Renal ca.   0.0   0.0       CAPAN 2           ACHN       Adrenal gland   0.3   0.9   Renal ca. UO-   0.0   0.0                   31       Thyroid   2.0   0.7   Renal ca. TK-   0.0   0.0                   10       Salivary gland   6.3   6.7   Liver   100.0   100.0       Pituitary gland   0.1   0.4   Liver (fetal)   37.9   58.2       Brain (fetal)   0.1   0.0   Liver ca.   0.0   0.0                   (hepatoblast)                   HepG2       Brain (whole)   1.2   0.1   Lung   0.4   0.8       Brain (amygdala)   0.0   0.1   Lung (fetal)   2.4   2.5       Brain   7.6   0.0   Lung ca. (small   0.0   0.0       (cerebellum)           cell) LX-1       Brain   0.1   0.2   Lung ca. (small   0.1   0.6       (hippocampus)           cell) NCI-H69       Brain (thalamus)   0.0   0.0   Lung ca. (s.cell   0.0   0.0                   var.) SHP-77       Cerebral Cortex   0.1   0.1   Lung ca. (large   0.0   0.2                   cell)NCI-H460       Spinal cord   0.0   0.1   Lung ca. (non-   0.1   0.2                   sm. cell) A549       glio/astro U87-   0.0   0.0   Lung ca. (non-   0.0   0.1       MG           s.cell) NCI-                   H23       glio/astro U-118-   0.0   0.0   Lung ca. (non-   0.0   0.0       MG           s.cell) HOP-62       astrocytoma   0.0   0.0   Lung ca. (non-   0.0   0.0       SW1783           s.cl) NCI-H522       neuro*; met SK-   0.0   0.0   Lung ca.   0.0   0.0       N-AS           (squam.) SW                   900       astrocytoma SF-   0.0   0.1   Lung ca.   0.1   0.2       539           (squam.) NCI-                   H596       astrocytoma   0.0   0.0   Mammary   2.9   2.3       SNB-75           gland       glioma SNB-19   0.0   0.1   Breast ca.*   0.0   0.0                   (pl.ef) MCF-7       glioma U251   0.0   0.1   Breast ca.*   0.0   0.0                   (pl.ef) MDA-                   MB-231       glioma SF-295   0.0   0.0   Breast ca.* (pl.   0.1   0.3                   ef) T47D       Heart   0.8   1.8   Breast ca. BT-   0.0   0.0                   549       Skeletal muscle   2.4   1.5   Breast ca.   0.0   0.1                   MDA-N       Bone marrow   2.7   3.5   Ovary   1.4   4.2       Thymus   0.2   0.3   Ovarian ca.   2.9   0.0                   OVCAR-3       Spleen   44.8   44.4   Ovarian ca.   4.1   0.0                   OVCAR-4       Lymph node   39.2   51.8   Ovarian ca.   0.2   0.3                   OVCAR-5       Colorectal   0.0   0.2   Ovarian ca.   0.0   0.1                   OVCAR-8       Stomach   1.0   2.9   Ovarian ca.   0.0   0.0                   IGROV-1       Samll intestine   1.2   2.7   Ovarian ca.   0.0   0.0                   (ascites) SK-                   OV-3       Colon ca. SW480   0.0   0.0   Uterus   0.2   0.7       Colon ca.*   0.0   0.0   Placenta   0.8   0.9       SW620 (SW480       met)       Colon ca. HT29   0.0   0.1   Prostate   0.3   0.5       Colon ca. HCT-   0.0   0.0   Prostate ca.*   0.0   0.0       116           (bone met) PC-3       Colon ca. CaCo-2   0.0   0.0   Testis   12.2   8.4       CC Well to Mod   0.1   0.4   Melanoma   0.0   0.0       Diff (ODO3866)           Hs688(A).T       Colon ca. HCC-   0.0   0.0   Melanoma*   0.0   0.1       2998           (met)                   Hs688(B).T       Gastric ca. (liver   0.0   0.1   Melanoma   0.0   0.0       met) NCI-N87           UACC-62       Bladder   3.7   3.8   Melanoma   0.1   0.2                   M14       Trachea   1.1   1.9   Melanoma   0.0   0.0                   LOX IMVI       Kidney   0.1   0.4   Melanoma*   0.1   0.0                   (met) SK-                   MEL-5       Kidney (fetal)   0.8   2.1                    
     [0710]               TABLE AL                          Panel 1.3D                                         Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)           Ag2742, Run   Ag2743, Run   Ag2744, Run   Ag2745, Run   Ag2746, Run       Tissue Name   153641674   153658349   153670718   153664738   153675151                                             Liver   0.0   0.0   0.0   0.0   0.0       adenocarcinoma       Pancreas   0.2   0.4   0.3   0.2   0.2       Pancreatic ca.   0.0   0.0   0.0   0.0   0.0       CAPAN 2       Adrenal gland   0.2   0.0   0.0   0.4   0.2       Thyroid   0.5   0.6   1.1   1.4   0.6       Salivary gland   1.0   1.0   0.7   0.7   0.1       Pituitary gland   0.0   0.0   0.1   0.0   0.0       Brain (fetal)   0.0   0.0   0.0   0.0   0.0       Brain (whole)   0.0   0.0   0.1   0.0   0.0       Brain (amygdala)   0.0   0.3   0.1   0.0   0.0       Brain   0.0   0.0   0.0   0.0   0.0       (cerebellum)       Brain   0.3   0.0   0.1   0.0   0.0       (hippocampus)       Brain (substantia   0.0   0.0   0.0   0.0   0.0       nigra)       Brain (thalamus)   0.0   0.0   0.0   0.0   0.0       Cerebral Cortex   0.0   0.0   0.0   0.1   0.0       Spinal cord   0.0   0.0   0.0   0.0   0.0       glio/astro U87-   0.0   0.0   0.0   0.0   0.0       MG       glio/astro U-118-   0.0   0.0   0.0   0.0   0.0       MG       astrocytoma   0.0   0.0   0.0   0.0   0.0       SW1783       neuro*; met SK-   0.0   0.0   0.0   0.0   0.0       N-AS       astrocytoma SF-   0.0   0.0   0.0   0.0   0.0       539       astrocytoma SNB-   0.0   0.0   0.0   0.0   0.0       75       glioma SNB-19   0.0   0.0   0.0   0.0   0.0       glioma U251   0.0   0.0   0.0   0.0   0.0       glioma SF-295   0.0   0.0   0.0   0.0   0.0       Heart (Fetal)   1.8   0.7   2.1   2.1   1.5       Heart   0.1   0.2   0.0   0.1   0.2       Skeletal muscle   8.5   6.9   9.3   9.5   6.8       (Fetal)       Skeletal muscle   0.0   0.0   0.0   0.1   0.0       Bone marrow   2.6   2.2   3.3   2.4   3.1       Thymus   0.1   0.0   0.1   0.1   0.2       Spleen   100.0   100.0   100.0   100.0   100.0       Lymph node   20.7   17.9   25.5   26.4   32.8       Colorectal   1.6   1.1   0.6   0.7   0.4       Stomach   1.3   0.5   1.2   0.7   0.9       Small intestine   1.3   1.0   1.1   1.1   1.2       Colon ca. SW480   0.0   0.0   0.0   0.0   0.0       Colon ca.*   0.0   0.0   0.0   0.0   0.0       SW620 (SW480       met)       Colon ca. HT29   0.0   0.0   0.0   0.0   0.0       Colon ca. HCT-   0.0   0.0   0.0   0.0   0.0       116       Colon ca. CaCo-2   0.0   0.0   0.0   0.0   0.0       CC Well to Mod   0.1   0.1   0.0   0.2   0.1       Diff (ODO3866)       Colon ca. HCC-   0.0   0.0   0.0   0.0   0.0       2998       Gastric ca. (liver   0.0   0.0   0.0   0.0   0.1       met) NCI-N87       Bladder   0.3   0.4   0.6   0.6   0.4       Trachea   1.3   0.7   1.4   1.2   1.3       Kidney   0.0   0.0   0.1   0.0   0.0       Kidney (fetal)   2.4   3.4   3.8   2.1   3.0       Renal ca. 786-0   0.0   0.0   0.0   0.0   0.0       Renal ca. A498   0.0   0.0   0.0   0.0   0.0       Renal ca. RXF   0.0   0.0   0.0   0.0   0.0       393       Renal ca. ACHN   0.0   0.0   0.0   0.0   0.0       Renal ca. UO-31   0.0   0.0   0.0   0.0   0.0       Renal ca. TK-10   0.0   0.0   0.0   0.0   0.0       Liver   5.6   8.8   6.1   6.4   10.3       Liver (fetal)   33.4   33.2   33.9   33.4   36.6       Liver ca.   0.0   0.0   0.0   0.0   0.0       (hepatoblast)       HepG2       Lung   0.6   0.6   0.6   0.7   0.2       Lung (fetal)   2.0   1.9   2.4   1.0   3.1       Lung ca. (small   0.0   0.0   0.0   0.0   0.0       cell) LX-1       Lung ca. (small   0.0   0.0   0.0   0.0   0.0       cell) NCI-H69       Lung ca. (s.cell   0.0   0.0   0.0   0.0   0.0       var.) SHP-77       Lung ca. (large   0.0   0.0   0.0   0.0   0.0       cell)NCI-H460       Lung ca. (non-sm.   0.0   0.0   0.0   0.0   0.0       cell) A549       Lung ca. (non-   0.0   0.0   0.0   0.0   0.0       s.cell) NCI-H23       Lung ca. (non-   0.0   0.0   0.0   0.0   0.0       s.cell) HOP-62       Lung ca. (non-   0.0   0.0   0.0   0.0   0.0       s.cl) NCI-H522       Lung ca. (squam.)   0.0   0.0   0.0   0.0   0.0       SW 900       Lung ca. (squam.)   0.0   0.0   0.0   0.0   0.0       NCI-H596       Mammary gland   1.6   1.5   1.1   1.7   1.5       Breast ca.* (pl.ef)   0.0   0.0   0.0   0.0   0.0       MCF-7       Breast ca.* (pl.ef)   0.0   0.0   0.0   0.0   0.0       MDA-MB-231       Breast ca.* (pl. ef)   0.0   0.0   0.0   0.0   0.0       T47D       Breast ca. BT-549   0.0   0.0   0.0   0.0   0.0       Breast ca. MDA-N   0.0   0.0   0.0   0.0   0.0       Ovary   5.0   5.4   4.5   6.0   4.6       Ovarian ca.   0.0   0.0   0.0   0.0   0.0       OVCAR-3       Ovarian ca.   0.0   0.0   0.0   0.0   0.0       OVCAR-4       Ovarian ca.   0.0   0.0   0.0   0.0   0.0       OVCAR-5       Ovarian ca.   0.0   0.0   0.0   0.0   0.0       OVCAR-8       Ovarian ca.   0.0   0.0   0.0   0.0   0.0       IGROV-1       Ovarian ca.   0.0   0.0   0.0   0.0   0.0       (ascites) SK-OV-3       Uterus   0.2   0.2   0.5   0.3   0.1       Placenta   0.4   0.0   0.4   0.1   0.2       Prostate   0.2   0.1   0.1   0.1   0.1       Prostate ca.*   0.0   0.0   0.0   0.0   0.0       (bone met) PC-3       Testis   7.5   5.9   4.7   6.5   5.6       Melanoma   0.0   0.0   0.0   0.0   0.0       Hs688(A).T       Melanoma* (met)   0.0   0.0   0.0   0.0   0.0       Hs688(B).T       Melanoma   0.0   0.0   0.0   0.0   0.0       UACC-62       Melanoma M14   0.0   0.0   0.0   0.0   0.0       Melanoma LOX   0.0   0.0   0.0   0.0   0.0       IMVI       Melanoma* (met)   0.0   0.0   0.0   0.0   0.0       SK-MEL-5       Adipose   1.0   1.5   0.6   0.5   1.1                    
     [0711]               TABLE AM                          Panel 2D                                         Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)           Ag2742, Run   Ag2743, Run   Ag2744, Run   Ag2745, Run   Ag2746, Run       Tissue Name   153641758   153658357   153670751   153664739   153675220                                             Normal Colon   3.2   3.8   4.4   4.8   4.5       CC Well to Mod   0.1   0.1   0.1   0.0   0.0       Diff (ODO3866)       CC Margin   0.7   0.5   0.9   1.2   0.3       (ODO3866)       CC Gr.2   0.2   0.4   0.2   0.2   0.1       rectosigmoid       (ODO3868)       CC Margin   0.1   0.1   0.0   0.2   0.1       (ODO3868)       CC Mod Diff   0.0   0.1   0.1   0.0   0.0       (ODO3920)       CC Margin   1.1   2.0   3.1   1.0   1.4       (ODO3920)       CC Gr.2 ascend   0.2   0.3   0.9   0.5   0.7       colon       (ODO3921)       CC Margin   0.7   0.3   0.9   1.0   0.2       (ODO3921)       CC from Partial   7.6   8.4   10.2   9.5   8.8       Hepatectomy       (ODO4309) Mets       Liver Margin   100.0   100.0   100.0   100.0   100.0       (ODO4309)       Colon mets to   0.4   0.3   0.3   1.5   0.4       lung (OD04451-       01)       Lung Margin   0.2   0.1   0.8   0.2   0.2       (OD04451-02)       Normal Prostate   0.4   0.0   0.2   0.1   0.1       6546-1       Prostate Cancer   0.2   0.2   0.0   0.3   0.0       (OD04410)       Prostate Margin   0.0   0.2   0.3   0.0   0.6       (OD04410)       Prostate Cancer   0.6   0.1   0.2   0.2   0.3       (OD04720-01)       Prostate Margin   0.5   0.5   0.6   0.3   0.2       (OD04720-02)       Normal Lung   5.6   5.2   6.3   8.1   5.9       Lung Met to   0.0   0.0   0.0   0.0   0.0       Muscle       (ODO4286)       Muscle Margin   0.5   0.0   0.1   0.2   0.0       (ODO4286)       Lung Malignant   1.0   1.0   1.3   0.8   1.0       Cancer       (OD03126)       Lung Margin   0.9   1.1   0.9   1.4   1.4       (OD03126)       Lung Cancer   1.3   0.8   1.6   1.5   1.4       (OD04404)       Lung Margin   2.0   2.5   4.3   3.4   3.2       (OD04404)       Lung Cancer   0.2   0.1   0.5   0.0   0.2       (OD04565)       Lung Margin   0.3   0.0   0.3   0.4   0.7       (OD04565)       Lung Cancer   0.4   0.9   1.2   1.5   1.2       (OD04237-01)       Lung Margin   5.6   5.4   7.9   6.3   5.6       (OD04237-02)       Ocular Mel Met   0.2   0.0   0.0   0.1   0.4       to Liver       (ODO4310)       Liver Margin   52.9   64.6   79.6   81.8   63.3       (ODO4310)       Melanoma   0.0   0.0   0.0   0.1   0.3       Metastasis       Lung Margin   0.2   2.0   0.9   1.5   0.5       (OD04321)       Normal Kidney   0.5   0.3   0.3   0.7   0.3       Kidney Ca,   0.0   0.1   0.0   0.0   0.1       Nuclear grade 2       (OD04338)       Kidney Margin   0.0   0.2   0.5   0.1   0.3       (OD04338)       Kidney Ca   0.0   0.0   0.0   0.0   0.0       Nuclear grade 1/2       (OD04339)       Kidney Margin   0.0   0.1   0.1   0.3   0.1       (OD04339)       Kidney Ca, Clear   0.0   0.1   0.0   0.0   0.1       cell type       (OD04340)       Kidney Margin   0.2   0.1   0.8   0.0   0.0       (OD04340)       Kidney Ca,   0.0   0.0   0.2   0.0   0.1       Nuclear grade 3       (OD04348)       Kidney Margin   0.0   0.1   0.2   0.1   0.1       (OD04348)       Kidney Cancer   0.2   0.1   0.1   1.2   0.2       (OD04622-01)       Kidney Margin   0.0   0.1   0.0   0.0   0.0       (OD04622-03)       Kidney Cancer   0.0   0.0   0.0   0.0   0.0       (OD04450-01)       Kidney Margin   0.1   0.0   0.1   0.1   0.1       (OD04450-03)       Kidney Cancer   0.0   0.0   0.0   0.0   0.0       8120607       Kidney Margin   0.1   0.0   0.2   0.0   0.0       8120608       Kidney Cancer   0.3   0.2   0.2   0.1   0.5       8120613       Kidney Margin   0.3   0.1   0.4   0.3   0.0       8120614       Kidney Cancer   0.0   0.1   0.1   0.1   0.2       9010320       Kidney Margin   0.1   0.0   0.0   0.1   0.2       9010321       Normal Uterus   0.5   0.1   0.8   0.1   0.5       Uterine Cancer   0.8   0.7   1.3   0.4   0.6       064011       Normal Thyroid   1.8   1.1   1.5   0.9   2.3       Thyroid Cancer   0.0   0.0   0.0   0.0   0.0       Thyroid Cancer   0.5   1.0   1.3   0.6   0.8       A302152       Thyroid Margin   2.3   2.4   3.5   3.9   2.4       A302153       Normal Breast   9.0   6.8   9.0   9.9   5.5       Breast Cancer   0.1   0.0   0.1   0.0   0.0       Breast Cancer   0.3   0.4   0.2   0.7   0.2       (OD04590-01)       Breast Cancer   1.7   2.4   2.5   2.5   1.4       Mets (OD04590-       03)       Breast Cancer   10.7   13.2   22.1   15.6   12.8       Metastasis       Breast Cancer   0.5   0.8   0.8   0.7   0.7       Breast Cancer   4.1   2.5   5.1   3.1   3.6       Breast Cancer   0.9   0.2   0.2   0.2   0.2       9100266       Breast Margin   0.7   0.4   1.0   0.7   1.2       9100265       Breast Cancer   1.2   1.2   1.1   1.9   0.8       A209073       Breast Margin   1.5   1.0   2.1   1.5   0.6       A2090734       Normal Liver   27.5   27.9   37.4   42.3   27.2       Liver Cancer   0.8   0.5   0.3   0.6   0.5       Liver Cancer   33.7   36.6   36.6   39.0   27.5       1025       Liver Cancer   4.6   3.6   5.7   5.8   5.2       1026       Liver Cancer   36.9   38.7   50.3   46.7   38.7       6004-T       Liver Tissue   1.5   1.0   1.3   1.3   1.6       6004-N       Liver Cancer   4.5   3.9   4.2   4.3   2.9       6005-T       Liver Tissue   22.2   24.5   32.8   27.5   28.7       6005-N       Normal Bladder   5.3   3.4   4.8   4.2   5.5       Bladder Cancer   1.6   1.3   1.5   1.6   1.7       Bladder Cancer   0.9   0.4   1.5   1.0   0.3       Bladder Cancer   0.0   0.0   0.0   0.0   0.0       (OD04718-01)       Bladder Normal   5.2   6.2   7.8   6.0   4.1       Adjacent       (OD04718-03)       Normal Ovary   1.6   3.0   5.4   3.6   3.6       Ovarian Cancer   0.0   0.1   0.1   0.6   0.5       Ovarian Cancer   0.0   0.0   0.0   0.1   0.0       (OD04768-07)       Ovary Margin   2.3   1.7   3.1   2.4   2.6       (OD04768-08)       Normal Stomach   0.9   0.8   1.7   0.8   0.8       Gastric Cancer   0.0   0.4   0.8   0.4   0.2       9060358       Stomach Margin   1.2   0.8   1.3   1.0   0.9       9060359       Gastric Cancer   0.1   0.2   0.3   0.5   0.6       9060395       Stomach Margin   0.8   0.6   1.7   0.7   0.6       9060394       Gastric Cancer   0.1   0.1   0.1   0.0   0.0       9060397       Stomach Margin   0.3   0.1   0.6   0.1   0.3       9060396       Gastric Cancer   0.7   0.6   0.4   1.1   0.3       064005                    
     [0712]               TABLE AN                          Panel 4D                                             Rel.   Rel.   Rel.   Rel.   Rel.   Rel.           Exp. (%)   Exp. (%)   Exp. (%)   Exp. (%)   Exp. (%)   Exp. (%)           Ag2742,   Ag2743,   Ag2744,   Ag2745,   Ag2746,   Ag812,           Run   Run   Run   Run   Run   Run       Tissue Name   153641803   153658360   153670759   153664740   153675321   138175358                                                 Secondary Th1 act   0.0   0.0   0.0   0.0   0.0   0.0       Secondary Th2 act   0.0   0.7   0.0   0.0   0.0   0.0       Secondary Tr1 act   1.7   0.0   1.9   0.0   7.5   2.8       Secondary Th1 rest   0.0   0.0   0.0   0.0   0.0   0.0       Secondary Th2 rest   0.0   0.0   0.0   0.0   0.0   0.0       Secondary Tr1 rest   0.0   0.0   0.0   0.0   0.0   2.8       Primary Th1 act   0.0   0.0   0.0   0.0   0.0   0.0       Primary Th2 act   1.6   0.0   0.0   0.0   0.0   4.8       Primary Tr1 act   0.0   0.0   0.0   0.0   0.0   0.0       Primary Th1 rest   0.0   0.0   0.0   0.0   0.0   0.0       Primary Th2 rest   0.0   0.0   0.0   0.0   0.0   0.0       Primary Tr1 rest   0.0   0.0   0.0   0.0   0.0   0.0       CD45RA CD4   0.0   0.0   0.0   0.0   0.0   0.0       lymphocyte act       CD45RO CD4   0.0   0.0   0.0   0.0   0.0   0.0       lymphocyte act       CD8 lymphocyte   0.0   0.0   0.0   0.0   0.0   0.0       act       Secondary CD8   0.0   0.0   0.0   0.0   0.0   0.0       lymphocyte rest       Secondary CD8   0.7   0.0   0.0   7.8   0.0   1.8       lymphocyte act       CD4 lymphocyte   0.0   0.0   0.0   0.0   0.0   0.0       none       2ry   0.0   0.0   0.0   0.0   0.0   0.0       Th1/Th2/Tr1_anti-       CD95 CH11       LAK cells rest   0.0   0.0   0.0   0.0   0.0   0.0       LAK cells IL-2   0.0   0.0   0.0   0.0   0.0   4.7       LAK cells IL-   0.0   0.0   0.0   0.0   1.9   0.0       2+IL-12       LAK cells IL-   0.0   1.5   3.3   5.0   0.0   3.0       2+IFN gamma       LAK cells IL-2+   0.0   0.0   2.1   0.0   0.0   0.0       IL-18       LAK cells   0.0   0.0   0.0   0.0   0.0   0.0       PMA/ionomycin       NK Cells IL-2 rest   0.0   0.0   0.0   0.0   0.0   0.0       Two Way MLR 3   0.0   0.0   0.0   0.0   0.0   0.0       day       Two Way MLR 5   0.0   0.0   0.0   0.0   0.0   0.0       day       Two Way MLR 7   2.0   0.0   6.4   0.0   0.0   11.3       day       PBMC rest   0.0   0.0   0.0   0.0   0.0   5.1       PBMC PWM   0.0   2.3   0.0   0.0   0.0   2.7       PBMC PHA-L   0.0   1.5   2.5   0.0   0.0   2.2       Ramos (B cell)   0.0   0.0   0.0   0.0   0.0   0.0       none       Ramos (B cell)   0.0   0.0   0.0   0.0   0.0   0.0       ionomycin       B lymphocytes   0.0   0.0   0.0   0.0   0.0   2.0       PWM       B lymphocytes   0.0   0.0   0.0   0.0   0.0   6.0       CD40L and IL-4       EOL-1 dbcAMP   0.0   0.0   0.0   0.0   0.0   0.0       EOL-1 dbcAMP   0.0   0.0   0.0   0.0   0.0   0.0       PMA/ionomycin       Dendritic cells   1.4   2.9   0.0   0.0   4.9   0.0       none       Dendritic cells LPS   0.0   0.0   0.0   0.0   0.0   0.0       Dendritic cells anti-   0.0   0.0   3.3   0.0   0.0   0.0       CD40       Monocytes rest   0.0   0.0   0.0   0.0   0.0   0.0       Monocytes LPS   0.0   0.0   0.0   0.0   0.0   0.0       Macrophages rest   0.0   0.0   0.0   0.0   0.0   0.0       Macrophages LPS   0.0   0.0   0.0   2.4   0.0   0.0       HUVEC none   0.0   0.0   0.0   0.0   0.0   0.0       HUVEC starved   0.0   0.0   0.0   0.0   0.0   0.0       HUVEC IL-1beta   0.0   0.0   0.0   0.0   0.0   0.0       HUVEC IFN   3.7   0.0   0.0   0.0   2.7   0.0       gamma       HUVEC TNF   0.0   0.0   0.0   0.0   0.0   0.0       alpha + IFN       gamma       HUVEC TNF   0.0   0.0   0.0   0.0   0.0   0.0       alpha + IL4       HUVEC IL-11   1.4   0.0   0.0   0.0   0.0   2.6       Lung   1.6   0.0   2.2   0.0   0.0   0.0       Microvascular EC       none       Lung   3.1   2.9   0.0   0.0   0.0   0.0       Microvascular EC       TNFalpha + IL-       1beta       Microvascular   0.0   3.1   5.0   0.0   0.0   12.6       Dermal EC none       Microsvasular   1.4   1.1   0.0   0.0   1.6   0.0       Dermal EC       TNFalpha + IL-       1beta       Bronchial   0.0   0.0   0.0   0.0   0.0   0.0       epithelium       TNFalpha +       IL1beta       Small airway   0.0   0.0   0.0   0.0   0.0   0.0       epithelium none       Small airway   0.0   0.0   0.0   0.0   0.0   0.0       epithelium       TNFalpha + IL-       1beta       Coronery artery   0.0   0.0   0.0   0.0   0.0   0.0       SMC rest       Coronery artery   0.0   0.0   0.0   0.0   0.0   0.0       SMC TNFalpha +       IL-1beta       Astrocytes rest   0.0   0.0   0.0   0.0   0.0   0.0       Astrocytes   0.0   0.0   0.0   0.0   0.0   0.0       TNFalpha + IL-       1beta       KU-812 (Basophil)   0.0   0.0   0.0   0.0   0.0   0.0       rest       KU-812 (Basophil)   0.0   0.0   0.0   0.0   0.0   0.0       PMA/ionomycin       CCD1106   0.0   0.0   0.0   0.0   0.0   0.0       (Keratinocytes)       none       CCD1106   0.0   0.0   0.0   0.0   0.0       (Keratinocytes)       TNFalpha + IL-       1beta       Liver cirrhosis   100.0   100.0   100.0   100.0   100.0   100.0       Lupus kidney   0.0   1.4   0.0   0.0   0.0   0.0       NCI-H292 none   0.0   0.0   0.0   0.0   0.0   0.0       NCI-H292 IL-4   0.0   0.0   0.0   0.0   2.3   0.0       NCI-H292 IL-9   0.0   0.0   0.0   0.0   0.0   0.0       NCI-H292 IL-13   0.0   0.0   0.0   0.0   0.0   0.0       NCI-H292 IFN   0.0   0.0   0.0   0.0   0.0   0.0       gamma       HPAEC none   4.8   1.4   0.0   0.0   0.0   3.0       HPAEC TNF alpha   0.0   0.0   0.0   0.0   0.0   0.0       + IL-1 beta       Lung fibroblast   0.0   0.0   0.0   0.0   0.0   0.0       none       Lung fibroblast   0.0   0.0   0.0   0.0   0.0   0.0       TNF alpha + IL-1       beta       Lung fibroblast IL-4   0.0   0.0   0.0   0.0   0.0   0.0       Lung fibroblast IL-9   0.0   0.0   0.0   0.0   0.0   0.0       Lung fibroblast IL-   0.0   0.0   0.0   0.0   0.0   0.0       13       Lung fibroblast   0.0   0.0   0.0   0.0   0.0   0.0       IFN gamma       Dermal fibroblast   0.0   0.0   0.0   0.0   0.0   0.0       CCD1070 rest       Dermal fibroblast   0.0   0.0   0.0   0.0   0.0   0.0       CCD1070 TNF       alpha       Dermal fibroblast   0.0   0.0   0.0   0.0   0.0   0.0       CCD1070 IL-1       beta       Dermal fibroblast   0.0   0.0   0.0   0.0   0.0   5.3       IFN gamma       Dermal fibroblast   0.0   0.0   0.0   0.0   0.0   0.0       IL-4       IBD Colitis 2   1.7   0.0   0.0   0.0   0.0   0.0       IBD Crohn&#39;s   4.5   1.6   6.7   6.1   3.3   3.0       Colon   5.5   2.1   23.0   8.3   4.7   11.1       Lung   41.5   26.2   27.7   39.2   37.1   49.7       Thymus   4.2   0.0   4.1   0.0   1.4   20.6       Kidney   4.7   5.2   8.7   5.9   6.3   6.7                    
     [0713] Panel 1 Summary: Ag03/Ag068  
     [0714] Two experiments with the same probe and primer set produce results that are in excellent agreement, with highest expression of the AC084364.5 gene in the spleen (CTs=21-25). Overall, this gene appears to be more highly expressed in normal tissue than in cancer cell lines. There are however detectable levels of expression in cell lines derived from melanoma, breast, renal, ovarian, lung, gastric and colon cancers. Thus, the difference in levels of expression of this gene could potentially be used to differentiate between these cancer cell line samples and other samples on this panel and between normal tissues and malignancies from those cancers.  
     [0715] There are also higher levels of expression in lung, and kidney tissue from fetal sources (CTs=25-28) when compared to levels of expression in the adult (CTs=38-31). Thus, expression of this gene could also be used to differentiate between adult and fetal lung and kidney tissue.  
     [0716] Among tissues with metabolic function, this gene is expressed in the liver, pituitary, thyroid, heart, skeletal muscle and adrenal gland. This suggests that the protein encoded by this gene may be invovled in the homeostasis of these tissues. Therefore, therapeutic modulation of the expression or function of this gene product may be effective in the treatment of metabolic disorders, including obesity and diabetes.  
     [0717] This gene is a homolog of Stabilin-1, and is also expressed at moderate levels in all brain regions examined. Because stabilin is involved in angiogenesis, the therapeutic modulation of this gene or its protein product may be of benefit in the treatment of stroke/cerebral ischemia/cerebral infarct.  
     [0718] Panel 1.2 Summary: Ag812  
     [0719] Two experiments with the same probe and primer set show highest expression of the AC084364.5 gene in the liver (CTs=25). Significant expression is also found in other metabolic tissues including fetal and adult heart, skeletal muscle, pancreas, thyroid, pituitary and adrenal gland. The high expression of this gene in the liver suggests that this gene may be involved in the normal homeostasis of that organ. Therapeutic modulation of the expression or function of this gene may be effective in the treatment of disease that involve the liver.  
     [0720] This gene also shows low to moderate expression in the brain. Please see Panel 1 for discussion of potential utility of this gene in the central nervous system.  
     [0721] While this gene shows a greater association for normal tissue, there are significant levels of expression in a cluster of ovarian cancer cell lines. Thus, expression of this gene could be used to differentiate between those samples and other samples on this panel, and between normal and malignant ovarian tissue. Furthermore, therapeutic modulation of the expression or function of this protein may be effective in the treatment of ovarian cancer. Please note that data from a third experiment with the probe and primer set Ag793 is not included, because the controls indicate that the experiment failed.  
     [0722] Panel 1.3D Summary: Ag2742, Ag2743, Ag2744, Ag2745, Ag2746  
     [0723] Multiple experiments with the same probe and primer set produce results that are in excellent agreement, with all experiments showing highest expression of the AC084364.5 gene in the liver (CTs=25). Significant expression is also found in the spleen (CTs=28-29). This result is in concordance with the results from Panel 1.  
     [0724] This gene appears to be expressed at higher levels in the fetal kidney and skeletal muscle (CTs=32-34) than in the comparable adult tissues (CTs=40). Thus, expression of this gene could be used to differentiate between kidney and skeletal muscle tissue from adult and fetal sources. Furthermore, the higher levels of expression of this gene in the fetal tissues suggest that this gene product may be involved in the development of these organs. Thus, therapeutic modulation of the expression or function of these genes may be effective in treating disease of these organs in the adult.  
     [0725] In this panel, this gene appears to exclusively associate with normal tissue samples, a preference that is also observed in panels 1 and 1.2. Thus, absence of expression of this gene may be useful in differentiating between the cancerous cell lines on this panel, and their corresponding normal tissues, specifically cancers of the ovary, breast and colon.  
     [0726] Panel 2D Summary: Ag2742/Ag2743/Ag2744/Ag2745/Ag2746  
     [0727] Multiple experiments with the same probe and primer set show expression of the AC084364.5 gene to be highest and almost exclusive in the liver (CTs=27-29). Furthermore, there is higher expression in liver tissue when compared to colon cancer or melanoma that have metastasized to the liver. This liver specific expression is in concordance with the results from previous panels. The low/undetectable levels of expression in cancer samples are also in agreement with the results observed in the preceding experiments. Thus, the expression profile of this gene suggests that expression of this gene could be used to differentiate between liver tissue and other samples on this panel and as a marker for liver tissue. Furthermore, therapeutic modulation of the expression or function of the protein encoded by this gene could be effective in the treatment of liver cancer or other disease that involve the liver. Additionally, slightly higher expression of this gene is seen in normal bladder, ovary and stomach compared to the adjacent tumor tissue. Hence, expression of this gene might be used as a marker to identify normal tissue from cancerous tissue in these organs. In addition, polypeptide molecules could potentially be used to therapeutically inhibit bladder, ovary and stomach cancer.  
     [0728] Panel 4D Summary: Ag812/Ag2742/Ag2743/Ag2744/Ag2745/Ag2746  
     [0729] The expression of the AC084364.5 gene appears to be highest in samples from cirrhotic liver, (CTs=32-33). Low level expression is also detected in samples derived from normal lung. The presence of this gene in liver cirrhosis (a component of which involves liver inflammation and fibrosis) suggests that therapeutic agents involving this gene may be useful in reducing or inhibiting the inflammation associated with fibrotic and other inflammatory diseases.  
     [0730] NOV2a and NOV2b (CG50646-04/cg142106342 and CG50646-05: Polydom Protein)  
     [0731] Expression of gene CG50646-04 and variant CG50646-05 was assessed using the primer-probe set Ag768, described in Table BA. Results of the RTQ-PCR runs are shown in Tables BB and BC.  
               TABLE BA                          Probe Name Ag768                                         Start       Primers   Sequences   Length   Position                                         Forward   5′-gggctataagtcagtcggaagt-3′   (SEQ ID NO:142)   22   6772               Probe   TET-5′-cctgtatttgtctgccaagccaatcg-3′-TAMRA   (SEQ ID NO:143)   26   6794               Reverse   5′-acagtcgagaggaacacacatc-3′   (SEQ ID NO:144)   22   6844                  
 
     [0732]               TABLE BB                          Panel 1.2                                 Rel. Exp.(%) Ag768,       Rel. Exp.(%) Ag768,       Tissue Name   Run 116422776   Tissue Name   Run 116422776               Endothelial cells   0.0   Renal ca. 786-0   0.0       Heart (Fetal)   0.0   Renal ca. A498   0.0       Pancreas   0.0   Renal ca. RXF 393   0.0       Pancreatic ca. CAPAN 2   0.0   Renal ca. ACHN   0.0       Adrenal gland   0.1   Renal ca. UO-31   0.0       Thyroid   0.0   Renal ca. TK-10   0.0       Salivary gland   0.0   Liver   0.0       Pituitary gland   0.0   Liver (fetal)   0.0       Brain (fetal)   0.0   Liver ca. (hepatoblast)   0.0               HepG2       Brain (whole)   0.0   Lung   0.6       Brain (amygdala)   0.0   Lung (fetal)   0.0       Brain (cerebellum)   0.0   Lung ca. (small cell)   0.0               LX-1       Brain (hippocampus)   0.0   (Lung ca. (small cell)   0.0               NCI-H69       Brain (thalamus)   0.0   Lung ca. (s. cell var.)   0.0               SHP-77       Cerebral Cortex   0.0   Lung ca. (large   0.0               cell)NCI-H460       Spinal cord   0.0   Lung ca. (non-sm.   0.0               cell) A549       glio/astro U87-MG   0.0   Lung ca. (non-s. cell)   0.0               NCI-H23       glio/astro U-118-MG   0.0   Lung ca. (non-s. cell)   0.0               HOP-62       astrocytoma SW1783   0.0   Lung ca. (non-s. cl)   0.0               NCI-H522       neuro*; met SK-N-AS   0.0   Lung ca. (squam.)   0.0               SW 900       astrocytoma SF-539   0.0   Lung ca. (squam.)   0.0               NCI-H596       astrocytoma SNB-75   0.0   Mammary gland   4.4       glioma SNB-19   0.0   Breast ca.* (pl. ef)   0.0               MCF-7       glioma U251   0.0   Breast ca.* (pl. ef)   0.0               MDA-MB-231       glioma SF-295   0.0   Breast ca.* (pl. ef)   0.0               T47D       Heart   0.1   Breast ca. BT-549   0.0       Skeletal muscle   0.2   Breast ca. MDA-N   0.0       Bone marrow   0.0   Ovary   0.0       Thymus   0.0   Ovarian ca. OVCAR-3   0.0       Spleen   0.0   Ovarian ca. OVCAR-4   0.0       Lymph node   0.7   Ovarian ca. OVCAR-5   0.0       Colorectal   0.0   Ovarian ca. OVCAR-8   0.0       Stomach   0.0   Ovarian ca. IGROV-1   0.0       Small intestine   0.8   Ovarian ca. (ascites)   0.0               SK-OV-3       Colon ca. SW480   0.0   Uterus   0.2       Colon ca.* SW620   0.0   Placenta   100.0       (SW480 met)       Colon ca. HT29   0.0   Prostate   0.0       Colon ca. HCT-116   0.0   Prostate ca.*   0.0               (bonemet) PC-3       Colon ca. CaCo-2   0.0   Testis   0.0       CC Well to Mod Diff   0.0   Melanoma   0.0       (ODO3866)       Hs688(A).T       Colon ca. HCC-2998   0.0   Melanoma* (met)   0.0               Hs688(B).T       Gastric ca. (liver met)   0.0   Melanoma UACC-62   0.0       NCI-N87       Bladder   0.0   Melanoma M14   0.0       Trachea   0.0   Melanoma LOX IMVI   0.0       Kidney   0.0   Melanoma* (met)   0.0               SK-MEL-5       Kidney (fetal)   0.0                    
     [0733]               TABLE BC                          Panel 4D                                 Rel. Exp.(%)       Rel. Exp.(%)           Ag768, Run       Ag768, Run       Tissue Name   138175130   Tissue Name   138175130                                     Secondary Th1 act   0.0   HUVEC IL-1beta   0.2       Secondary Th2 act   0.1   HUVEC IFN gamma   0.3       Secondary Tr1 act   0.0   HUVEC TNF alpha + IFN   0.1               gamma       Secondary Th1 rest   0.1   HUVEC TNF alpha + IL4   0.1       Secondary Th2 rest   0.1   HUVEC IL-11   0.1       Secondary Tr1 rest   0.2   Lung Microvascular EC none   0.0       Primary Th1 act   0.0   Lung Microvascular EC   0.0               TNFalpha + IL-1beta       Primary Th2 act   0.0   Microvascular Dermal EC   0.1               none       Primary Tr1 act   0.0   Microsvasular Dermal EC   0.2               TNFalpha + IL-1beta       Primary Th1 rest   0.2   Bronchial epithelium   0.2               TNFalpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium none   2.3       Primary Tr1 rest   0.0   Small airway epithelium   1.3               TNFalpha + IL-1beta       CD45RA CD4   6.4   Coronery artery SMC rest   15.1       lymphocyte act       CD45RO CD4   0.1   Coronery artery SMC   8.2       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   1.8       Secondary CD8   0.1   Astrocytes TNFalpha + IL-   2.4       lymphocyte rest       1beta       Secondary CD8   0.1   KU-812 (Basophil) rest   0.0       lymphocyte act       CD4 lymphocyte none   0.0   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.0   CCD1106 (Keratinocytes)   0.4       CD95 CH11       none       LAK cells rest   0.2   93580_CCD1106   1.4               (Keratinocytes)_TNFa and               IFNg       LAK cells IL-2   0.0   Liver cirrhosis   10.6       LAK cells IL-2 + IL-12   0.1   Lupus kidney   7.0       LAK cells IL-2 + IFN   0.3   NCI-H292 none   24.1       gamma       LAK cells IL-2 + IL-18   0.2   NCI-H292 IL-4   21.6       LAK cells   3.5   NCI-H292 IL-9   30.4       PMA/ionomycin       NK Cells IL-2 rest   0.0   NCI-H292 IL-13   15.3       Two Way MLR 3 day   0.0   NCI-H292 IFN gamma   14.6       Two Way MLR 5 day   0.0   HPAEC none   0.4       Two Way MLR 7 day   0.0   HPAEC TNF alpha + IL-1 beta   0.0       PBMC rest   0.0   Lung fibroblast none   31.0       PBMC PWM   2.5   Lung fibroblast TNF alpha +   7.7               IL-1 beta       PBMC PHA-L   0.3   Lung fibroblast IL-4   55.5       Ramos (B cell) none   0.0   Lung fibroblast IL-9   37.4       Ramos (B cell)   0.1   Lung fibroblast IL-13   86.5       ionomycin       B lymphocytes PWM   0.1   Lung fibroblast IFN gamma   100.0       B lymphocytes CD40L   0.0   Dermal fibroblast CCD1070   28.9       and IL-4       rest       EOL-1 dbcAMP   0.0   Dermal fibroblast CCD1070   23.7               TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast CCD1070   20.2       PMA/ionomycin       IL-1 beta       Dendritic cells none   0.0   Dermal fibroblast IFN gamma   22.5       Dendritic cells LPS   0.2   Dermal fibroblast IL-4   47.0       Dendritic cells anti-   0.1   IBD Colitis 2   0.5       CD40       Monocytes rest   0.1   IBD Crohn&#39;s   2.0       Monocytes LPS   3.1   Colon   9.2       Macrophages rest   0.1   Lung   20.3       Macrophages LPS   3.3   Thymus   13.0       HUVEC none   0.0   Kidney   6.4       HUVEC starved   0.2                    
     [0734] Panel 1.2 Summary: Ag768  
     [0735] Highest expression of the CG50646-04 (NOV2a) gene is seen in placenta (CT=21). This gene encodes a polydom-like protein and is also highly expressed in mammary gland, skeletal muscle. This gene may be involved in cellular adhesion (ref. 1). Thus, expression of this gene may be used to differentiate between placental tissues and other tissues on this panel. Modulation of this gene or its protein product may be useful in reproductive and skeletal muscle physiology.  
     [0736] This gene is more highly expressed in fetal kidney (CT=33) than in adult kidney (CT=40). Conversely, this gene is more highly expressed in adult lung and liver (CTs=28-32) than in fetal lung and liver (CTs=38-40). Thus, expression of this gene could be used to differentiate between the adult and fetal sources of these tissues.  
     [0737] References:  
     [0738] Gilges D, Vinit M A, Callebaut I, Coulombel L, Cacheux V, Romeo P H, Vigon I. Polydom: a secreted protein with pentraxin, complement control protein, epidermal growth factor and von Willebrand factor A domains. Biochem J Nov. 15, 2000;352 Pt 1:49-59  
     [0739] To identify extracellular proteins with epidermal growth factor (EGF) domains that are potentially involved in the control of haemopoiesis, we performed degenerate reverse-transcriptase-mediated PCR on the murine bone-marrow stromal cell line MS-5 and isolated a new partial cDNA encoding EGF-like domains related to those in the Notch proteins. Cloning and sequencing of the full-length cDNA showed that it encoded a new extracellular multidomain protein that we named polydom. This 387 kDa mosaic protein contained a signal peptide followed by a new association of eight different protein domains, including a pentraxin domain and a von Willebrand factor type A domain, ten EGF domains, and 34 complement control protein modules. The human polydom mRNA is strongly expressed in placenta, its expression in the other tissues being weak or undetectable. The particular multidomain structure of the encoded protein suggests an important biological role in cellular adhesion and/or in the immune system.  
     [0740] PMID: 11062057  
     [0741] Panel 4D Summary: Ag768  
     [0742] Highest expression of the CG50646-04 gene is seen in lung fibroblasts stimulated with IFN-gamma (CT=27.4). Significant expression is seen in many samples derived from the lung including lung fibroblasts stimulated with different cytokines, the pulmonary mucoepidermoid cell line H292 stimulated with the same cytokines, and normal lung tissue. The expression of this gene in lung cells and lung tissue suggests that this gene may be involved in normal homeostasis of the lung, as well as pathological and inflammatory lung disorders, including chronic obstructive pulmonary disease, asthma, allergy and emphysema.  
     [0743] Significant levels of expression of this gene in dermal fibroblasts suggests that this gene may be involved in skin disorders, including psoriasis.  
     [0744] Moderate to low expression of this gene is also seen in many other cells with important immune function, including stimulated macrophages and monocytes, coronary artery smooth muscle cells, stimulated peripheral blood mononuclear cells, lymphocyte activated killer cells (LAK), astrocytes, activated CD45RA cells, and normal colon, thymus and kidney. This widespread expression suggests that this protein encoded by this gene may be involved in other inflammatory and autoimmune conditions, including inflammatory bowel disease, rheumatoid arthritis and osteoarthritis.  
     [0745] NOV3a and NOV3b (CG50273-01 and CG50273-02/152792120: Novel Transmembrane Protein)  
     [0746] Expression of gene CG50273-01 and variant CG50273-02 was assessed using the primer-probe set Ag2556, described in Table CA. Results of the RTQ-PCR runs are shown in Tables CB, CC, CD, CE, CF and CG.  
               TABLE CA                          Probe Name Ag2556                                         Start       Primers   Sequences   Length   Position                                         Forward   5′-gaggacagctttgatttcattg-3′   (SEQ ID NO:145)   22   526               Probe   TET-5′-tggatttgatccatttcctctctacca-3′-TAMRA   (SEQ ID NO:146)   27   549               Reverse   5′-aagagactggatggcttttcat-3′   (SEQ ID NO:147)   22   581                  
 
     [0747]               TABLE CB                          CNS_neurodegeneration_v1.0                                 Rel. Exp.(%) Ag2556,       Rel. Exp.(%) Ag2556,       Tissue Name   Run 206974724   Tissue Name   Run 206974724                                     AD 1 Hippo   22.4   Control (Path) 3   6.9               Temporal Ctx       AD 2 Hippo   100.0   Control (Path) 4   21.8               Temporal Ctx       AD 3 Hippo   3.7   AD 1 Occipital Ctx   6.1       AD 4 Hippo   33.0   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   21.9   AD 3 Occipital Ctx   2.1       AD 6 Hippo   71.2   AD 4 Occipital Ctx   21.9       Control 2 Hippo   55.5   AD 5 Occipital Ctx   18.2       Control 4 Hippo   55.5   AD 5 Occipital Ctx   3.0       Control (Path) 3   14.4   Control 1 Occipital   2.3       Hippo       Ctx       AD 1 Temporal Ctx   14.1   Control 2 Occipital   19.5               Ctx       AD 2 Temporal Ctx   57.4   Control 3 Occipital   9.3               Ctx       AD 3 Temporal Ctx   5.3   Control 4 Occipital   13.6               Ctx       AD 4 Temporal Ctx   39.5   Control (Path) 1   41.5               Occipital Ctx       AD 5 Inf Temporal   42.0   Control (Path) 2   6.1       Ctx       Occipital Ctx       AD 5 Sup Temporal   66.0   Control (Path) 3   1.8       Ctx       Occipital Ctx       AD 6 Inf Temporal   26.1   Control (Path) 4   9.0       Ctx       Occipital Ctx       AD 6 Sup Temporal   14.1   Control 1 Parietal   12.0       Ctx       Ctx       Control 1 Temporal   18.8   Control 2 Parietal   41.5       Ctx       Ctx       Control 2 Temporal   29.3   Control 3 Parietal   12.6       Ctx       Ctx       Control 3 Temporal   14.0   Control (Path) 1   27.9       Ctx       Parietal Ctx       Control 3 Temporal   26.1   Control (Path) 2   16.6       Ctx       Parietal Ctx       Control (Path) 1   43.8   Control (Path) 3   2.9       Temporal Ctx       Parietal Ctx       Control (Path) 2   42.0   Control (Path) 4   17.6       Temporal Ctx       Parietal Ctx                    
     [0748]               TABLE CC                          Panel 1.3D                                 Rel. Exp. (%) Ag2556,       Rel. Exp. (%) Ag2556,       Tissue Name   Run 162292610   Tissue Name   Run 162292610                                     Liver adenocarcinoma   0.0   Kidney (fetal)   5.6       Pancreas   0.0   Renal ca. 786-0   6.3       Pancreatic ca. CAPAN 2   0.0   Renal ca. A498   0.5       Adrenal gland   0.7   Renal ca. RXF 393   2.0       Thyroid   0.4   Renal ca. ACHN   3.3       Salivary gland   0.6   Renal ca. UO-31   0.9       Pituitary gland   2.8   Renal ca. TK-10   24.3       Brain (fetal)   3.7   Liver   0.0       Brain (whole)   22.7   Liver (fetal)   0.0       Brain (amygdala)   59.9   Liver ca.   0.0               (hepatoblast) HepG2       Brain (cerebellum)   39.0   Lung   0.0       Brain (hippocampus)   83.5   Lung (fetal)   0.0       Brain (substantia nigra)   30.8   Lung ca. (small cell)   0.0               LX-1       Brain (thalamus)   40.3   Lung ca. (small cell)   0.0               NCI-H69       Cerebral Cortex   55.9   Lung ca. (s.cell var.)   0.0               SHP-77       Spinal cord   72.2   Lung ca. (large   0.0               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)   0.0               NCI-H522       astrocytoma SF-539   0.0   Lung ca. (squam.)   0.5               SW 900       astrocytoma SNB-75   0.0   Lung ca. (squam.)   0.0               NCI-H596       glioma SNB-19   0.4   Mammary gland   0.0       glioma U251   0.0   Breast ca.* (pl. ef)   0.0               MCF-7       glioma SF-295   0.0   Breast ca.* (pl. ef)   0.0               MDA-MB-231       Heart (Fetal)   4.5   Breast ca.* (pl. ef)   0.0               T47D       Heart   0.0   Breast ca. BT-549   0.0       Skeletal muscle (Fetal)   100.0   Breast ca. MDA-N   0.0       Skeletal muscle   0.0   Ovary   0.4       Bone marrow   0.0   Ovarian ca. OVCAR-3   0.0       Thymus   5.2   Ovarian ca. OVCAR-4   0.7       Spleen   0.0   Ovarian ca. OVCAR-5   2.0       Lymph node   0.0   Ovarian ca. OVCAR-8   0.9       Colorectal   2.7   Ovarian ca. IGROV-1   0.0       Stomach   0.0   Ovarian ca. (ascites)   20.7               SK-OV-3       Small intenstine   0.8   Uterus   0.5       Colon ca. SW480   0.0   Placenta   11.0       Colon ca.* SW620   0.0   Prostate   0.0       (SW480 met)       Colon ca. HT29   0.0   Prostate ca.*   0.0               (bonemet) PC-3       Colon ca. HCT-116   0.0   Testis   5.6       Colon ca. CaCo-2   7.3   Melanoma   0.0               Hs688(A).T       CC Well to Mod Diff   0.5   Melanoma* (met)   0.0       (ODO3866)       Hs688(B).T       Colon ca. HCC-2998   0.0   Melanoma UACC-62   0.0       Gastric ca. (liver met)   0.0   Melanoma M14   0.0       NCI-N87       Bladder   0.0   Melanoma LOX   0.0               IMVI       Trachea   1.1   Melanoma* (met)   0.0               SK-MEL-5       Kidney   20.4   Adipose   0.8                    
     [0749]               TABLE CD                          Panel 2D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2556,       Ag2556,       Tissue Name   Run 161921170   Tissue Name   Run 161921170                                     Normal Colon   1.0   Kidney Margin   30.6               8120608       CC Well to Mod Diff   0.0   Kidney Cancer   0.3       (ODO3866)       8120613       CC Margin (ODO3866)   0.1   Kidney Margin   4.1               8120614       CC Gr.2 rectosigmoid   0.0   Kidney Cancer   3.7       (ODO3868)       9010320       CC Margin (ODO3868)   0.1   Kidney Margin   100.0               9010321       CC Mod Diff (ODO3920)   0.3   Normal Uterus   0.0       CC Margin (ODO3920)   0.0   Uterine Cancer   0.0               064011       CC Gr.2 ascend colon   0.3   Normal Thyroid   0.8       (ODO3921)       CC Margin (ODO3921)   0.0   Thyroid Cancer   0.4       CC from Partial   0.3   Thyroid Cancer   1.5       Hepatectomy (ODO4309)       A302152       Mets       Liver Margin (ODO4309)   0.0   Thyroid Margin   1.4               A302153       Colon mets to lung   0.0   Normal Breast   0.0       (OD04451-01)       Lung Margin (OD04451-   0.1   Breast Cancer   0.0       02)       Normal Prostate 6546-1   0.2   Breast Cancer   0.0               (OD04590-01)       Prostate Cancer   0.1   Breast Cancer Mets   0.0       (OD04410)       (OD04590-03)       Prostate Margin   0.3   Breast Cancer   0.0       (OD04410)       Metastasis       Prostate Cancer   0.3   Breast Cancer   0.2       (OD04720-01)       Prostate Margin   0.0   Breast Cancer   0.1       (OD04720-02)       Normal Lung   0.1   Breast Cancer   0.0               9100266       Lung Met to Muscle   0.0   Breast Margin   0.1       (ODO4286)       9100265       Muscle Margin   0.0   Breast Cancer   0.0       (ODO4286)       A209073       Lung Malignant Cancer   1.0   Breast Margin   0.0       (OD03126)       A2090734       Lung Margin (OD03126)   0.1   Normal Liver   0.0       Lung Cancer (OD04404)   0.0   Liver Cancer   0.0       Lung Margin (OD04404)   0.0   Liver Cancer 1025   0.0       Lung Cancer (OD04565)   0.2   Liver Cancer 1026   0.0       Lung Margin (OD04565)   0.0   Liver Cancer 6004-T   0.0       Lung Cancer (OD04237-   0.1   Liver Tissue 6004-N   0.0       01)       Lung Margin (OD04237-   0.1   Liver Cancer 6005-T   0.0       02)       Ocular Mel Met to Liver   1.0   Liver Tissue 6005-N   0.0       (ODO4310)       Liver Margin (ODO4310)   0.0   Normal Bladder   0.0       Melanoma Metastasis   0.3   Bladder Cancer   0.0       Lung Margin (OD04321)   0.0   Bladder Cancer   0.0       Normal Kidney   2.4   Bladder Cancer   0.9               (OD04718-01)       Kidney Ca, Nuclear grade   15.1   Bladder Normal   0.0       2 (OD04338)       Adjacent (OD04718-               03)       Kidney Margin   16.0   Normal Ovary   0.0       (OD04338)       Kidney Ca Nuclear grade   3.7   Ovarian Cancer   0.1       1/2 (OD04339)       Kidney Margin   15.9   Ovarian Cancer   0.2       (OD04339)       (OD04768-07)       Kidney Ca, Clear cell type   1.6   Ovary Margin   0.1       (OD04340)       (OD04768-08)       Kidney Margin   3.3   Normal Stomach   0.3       (OD04340)       Kidney Ca, Nuclear grade   0.1   Gastric Cancer   0.2       3 (OD04348)       9060358       Kidney Margin   20.3   Stomach Margin   0.0       (OD04348)       9060359       Kidney Cancer   8.8   Gastric Cancer   0.2       (OD04622-01)       9060395       Kidney Margin   6.0   Stomach Margin   0.1       (OD04622-03)       9060394       Kidney Cancer   1.9   Gastric Cancer   0.3       (OD04450-01)       9060397       Kidney Margin   1.9   Stomach Margin   0.0       (OD04450-03)       9060396       Kidney Cancer 8120607   0.2   Gastric Cancer 064005   0.3                    
     [0750]               TABLE CE                          Panel 3D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2556, Run       Ag2556, Run       Tissue Name   164827571   Tissue Name   164827571                                     Daoy-Medulloblastoma   1.8   Ca Ski-Cervical epidermoid   0.0               carcinoma (metastasis)       TE671-Medulloblastoma   100.0   ES-2-Ovarian clear cell   0.0               carcinoma       D283 Med-   0.0   Ramos-Stimulated with   0.0       Medulloblastoma       PMA/ionomycin 6h       PFSK-1-Primitive   0.0   Ramos-Stimulated with   0.0       Neuroectodermal       PMA/ionomycin 14h       XF-498-CNS   0.5   MEG-01-Chronic   0.0               myelogenous leukemia               (megokaryoblast)       SNB-78-Glioma   0.4   Raji-Burkitt&#39;s lymphoma   0.0       SF-268-Glioblastoma   0.0   Daudi-Burkitt&#39;s lymphoma   0.0       T98G-Glioblastoma   0.0   U266-B-cell plasmacytoma   0.0       SK-N-SH-   0.0   CA46-Burkitt&#39;s lymphoma   0.0       Neuroblastoma       (metastasis)       SF-295-Glioblastoma   0.0   RL-non-Hodgkin&#39;s B-cell   0.0               lymphoma       Cerebellum   30.8   JM1-pre-B-cell lymphoma   0.3       Cerebellum   49.3   Jurkat-T cell leukemia   0.0       NCI-H292-   0.0   TF-1-Erythroleukemia   0.0       Mucoepidermoid lung       carcinoma       DMS-114-Small cell   1.1   HUT 78-T-cell lymphoma   0.3       lung cancer       DMS-79-Small cell lung   32.5   U937-Histiocytic lymphoma   0.0       cancer       NCI-H146-Small cell   0.0   KU-812-Myelogenous   0.0       lung cancer       leukemia       NCI-H526-Small cell   0.0   769-P-Clear cell renal   2.4       lung cancer       carcinoma       NCI-N417-Small cell   0.0   Caki-2-Clear cell renal   0.6       lung cancer       carcinoma       NCI-H82-Small cell lung   0.0   SW 839-Clear cell renal   0.0       cancer       carcinoma       NCI-H157-Squamous   0.0   G401-Wilms&#39; tumor   9.5       cell lung cancer       (metastasis)       NCI-H1155-Large cell   0.0   Hs766T-Pancreatic carcinoma   0.0       lung cancer       (LN metastasis)       NCI-H1299-Large cell   0.0   CAPAN-1-Pancreatic   0.0       lung cancer       adenocarcinoma (liver               metastasis)       NCI-H727-Lung   4.1   SU86.86-Pancreatic   0.6       carcinoid       carcinoma (liver metastasis)       NCI-UMC-11-Lung   0.0   BxPC-3-Pancreatic   0.0       carcinoid       adenocarcinoma       LX-1-Small cell lung   0.4   HPAC-Pancreatic   1.0       cancer       adenocarcinoma       Colo-205-Colon cancer   0.0   MIA PaCa-2-Pancreatic   1.9               carcinoma       KM12-Colon cancer   0.0   CFPAC-1-Pancreatic ductal   0.0               adenocarcinoma       KM20L2-Colon cancer   0.0   PANC-1-Pancreatic   7.7               epithelioid ductal carcinoma       NCI-H716-Colon cancer   0.0   T24-Bladder carcinma   0.3               (transitional cell)       SW-48-Colon   0.0   5637-Bladder carcinoma   0.0       adenocarcinoma       SW1116-Colon   0.0   HT-1197-Bladder carcinoma   3.7       adenocarcinoma       LS 174T-Colon   0.0   UM-UC-3-Bladder carcinma   0.0       adenocarcinoma       (transitional cell)       SW-948-Colon   0.0   A204-Rhabdomyosarcoma   0.0       adenocarcinoma       SW-480-Colon   0.0   HT-1080-Fibrosarcoma   0.0       adenocarcinoma       NCI-SNU-5-Gastric   0.0   MG-63-Osteosarcoma   0.4       carcinoma       KATO III-Gastric   0.0   SK-LMS-1-Leiomyosarcoma   0.0       carcinoma       (vulva)       NCI-SNU-16-Gastric   0.0   SJRH30-Rhabdomyosarcoma   3.0       carcinoma       (met to bone marrow)       NCI-SNU-1-Gastric   0.0   A431-Epidermoid carcinoma   0.0       carcinoma       RF-1-Gastric   0.0   WM266-4-Melanoma   0.0       adenocarcinoma       RF-48-Gastric   0.0   DU 145-Prostate carcinoma   0.0       adenocarcinoma       (brain metastasis)       MKN-45-Gastric   0.0   MDA-MB-468-Breast   0.0       carcinoma       adenocarcinoma       NCI-N87-Gastric   0.0   SCC-4-Squamous cell   0.0       carcinoma       carcinoma of tongue       OVCAR-5-Ovarian   0.0   SCC-9-Squamous cell   0.0       carcinoma       carcinoma of tongue       RL95-2-Uterine   0.0   SCC-15-Squamous cell   0.0       carcinoma       carcinoma of tongue       HelaS3-Cervical   0.0   CAL 27-Squamous cell   0.0       adenocarcinoma       carcinoma of tongue                    
     [0751]               TABLE CF                          Panel 4D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2556, Run       Ag2556, Run       Tissue Name   164035630   Tissue Name   164035630                                     Secondary Th1 act   0.0   HUVEC IL-1beta   0.0       Secondary Th2 act   0.0   HUVEC IFN gamma   0.0       Secondary Tr1 act   0.0   HUVEC TNF alpha + IFN   0.0               gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha + IL4   0.0       Secondary Th2 rest   0.0   HUVEC IL-11   0.0       Secondary Tr1 rest   0.0   Lung Microvascular EC   0.0               none       Primary Th1 act   0.0   Lung Microvascular EC   0.0               TNFalpha + IL-1beta       Primary Th2 act   0.0   Microvascular Dermal EC   0.0               none       Primary Tr1 act   0.0   Microsvasular Dermal EC   0.0               TNFalpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   0.7               TNFalpha + IL-1beta       Primary Th2 rest   0.0   Small airway epithelium   1.4               none       Primary Tr1 rest   0.0   Small airway epithelium   5.0               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   0.0       Secondary CD8   0.0   Astrocytes TNFalpha + IL-   0.0       lymphocyte rest       1beta       Secondary CD8   0.0   KU-812 (Basophil) rest   0.0       lymphocyte act       CD4 lymphocyte none   0.0   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.0   CCD1106 (Keratinocytes)   0.0       CD95 CH11       none       LAK cells rest   0.0   CCD1106 (Keratinocytes)   0.0               TNFalpha + IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   0.0       LAK cells IL-2 + IL-12   0.0   Lupus kidney   3.2       LAK cells IL-2 + IFN   0.0   NCI-H292 none   0.0       gamma       LAK cells IL-2 + IL-18   0.0   NCI-H292 IL-4   0.0       LAK cells   0.0   NCI-H292 IL-9   0.0       PMA/ionomycin       NK Cells IL-2 rest   0.0   NCI-H292 IL-13   0.0       Two Way MLR 3 day   0.0   NCI-H292 IFN gamma   0.0       Two Way MLR 5 day   0.0   HPAEC none   0.0       Two Way MLR 7 day   0.0   HPAEC TNF alpha + IL-   0.0               1beta       PBMC rest   0.0   Lung fibroblast none   0.0       PBMC PWM   0.0   Lung fibroblast TNF   0.0               alpha + IL-1beta       PBMC PHA-L   0.0   Lung fibroblast IL-4   0.0       Ramos (B cell) none   0.0   Lung fibroblast IL-9   0.0       Ramos (B cell)   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   0.0   Dermal fibroblast   0.0               CCD1070 TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast   0.0       PMA/ionomycin       CCD1070 IL-1beta       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   0.0   IBD Crohn&#39;s   0.0       Monocytes LPS   0.0   Colon   5.2       Macrophages rest   0.0   Lung   1.3       Macrophages LPS   0.0   Thymus   100.0       HUVEC none   0.0   Kidney   12.9       HUVEC starved   0.0                    
     [0752]               TABLE CG                          Panel CNS_1                                 Rel. Exp. (%) Ag2556,       Rel. Exp. (%) Ag2556,       Tissue Name   Run 171656437   Tissue Name   Run 171656437                                     BA4 Control   15.2   BA17 PSP   8.5       BA4 Control2   21.9   BA17 PSP2   0.0       BA4   4.4   Sub Nigra Control   66.9       Alzheimer&#39;s2       BA4 Parkinson&#39;s   34.9   Sub Nigra Control2   41.2       BA4   12.9   Sub Nigra   33.4       Parkinson&#39;s2       Alzheimer&#39;s2       BA4   28.9   Sub Nigra   71.7       Huntington&#39;s       Parkinson&#39;s2       BA4   16.5   Sub Nigra   92.7       Huntington&#39;s2       Huntington&#39;s       BA4 PSP   7.0   Sub Nigra   12.9               Huntington&#39;s2       BA4 PSP2   18.3   Sub Nigra PSP2   20.6       BA4 Depression   12.2   Sub Nigra   10.2               Depression       BA4   3.5   Sub Nigra   5.9       Depression2       Depression2       BA7 Control   5.8   Glob Palladus   40.9               Control       BA7 Control2   17.0   Glob Palladus   34.6               Control2       BA7   10.9   Glob Palladus   42.9       Alzheimer&#39;s2       Alzheimer&#39;s       BA7 Parkinson&#39;s   30.4   Glob Palladus   14.8               Alzheimer&#39;s2       BA7   8.2   Glob Palladus   100.0       Parkinson&#39;s2       Parkinson&#39;s       BA7   19.8   Glob Palladus   20.6       Huntington&#39;s       Parkinson&#39;s2       BA7   32.8   Glob Palladus PSP   16.5       Huntington&#39;s2       BA7 PSP   16.3   Glob Palladus PSP2   23.0       BA7 PSP2   12.1   Glob Palladus   13.4               Depression       BA7 Depression   4.9   Temp Pole Control   10.8       BA9 Control   17.0   Temp Pole Control2   58.6       BA9 Control2   54.0   Temp Pole   27.5               Alzheimer&#39;s       BA9 Alzheimer&#39;s   10.3   Temp Pole   13.4               Alzheimer&#39;s2       BA9   26.8   Temp Pole   34.4       Alzheimer&#39;s2       Parkinson&#39;s       BA9 Parkinson&#39;s   33.0   Temp Pole   35.4               Parkinson&#39;s2       BA9   28.7   Temp Pole   57.8       Parkinson&#39;s2       Huntington&#39;s       BA9   58.2   Temp Pole PSP   8.8       Huntington&#39;s       BA9   27.9   Temp Pole PSP2   8.9       Huntington&#39;s2       BA9 PSP   17.1   Temp Pole   8.4               Depression2       BA9 PSP2   3.6   Cing Gyr Control   51.1       BA9 Depression   6.8   Cing Gyr Control2   33.7       BA9   5.8   Cing Gyr Alzheimer&#39;s   49.0       Depression2       BA17 Control   9.4   Cing Gyr   11.1               Alzheimer&#39;s2       BA17 Control2   14.2   Cing Gyr Parkinson&#39;s   61.1       BA17   4.4   Cing Gyr   42.0       Alzheimer&#39;s2       Parkinson&#39;s2       BA17   22.8   Cing Gyr   77.4       Parkinson&#39;s       Huntington&#39;s       BA17   4.9   Cing Gyr   38.2       Parkinson&#39;s2       Huntington&#39;s2       BA17   14.6   Cing Gyr PSP   20.0       Huntington&#39;s       BA17   8.8   Cing Gyr PSP2   25.0       Huntington&#39;s2       BA17   7.2   Cing Gyr Depression   23.7       Depression       BA17   4.6   Cing Gyr   11.3       Depression2       Depression2                    
     [0753] CNS_Neurodegeneration —v 1.0 Summary: Ag2556  
     [0754] No difference was detected in the expression of the CG50273-01 gene in the postmortem brains of Alzheimer&#39;s patients when compared normal controls; however this panel demonstrates the expression of this gene in the CNS of an independent group of patients. See panel 1.3d for discussion of utility of this gene in the central nervous system.  
     [0755] Panel 1.3D Summary: Ag2556  
     [0756] Highest expression of the CG50273-01 gene is seen in fetal skeletal muscle (CT=31.4). Furthermore, this gene appears to be expressed at much higher levels in fetal skeletal muscle than in the adult (CT=40). This expression pattern suggests that the protein encoded by this gene may be involved in the development of this tissue. Furthermore, therapeutic application of the protein product may help in restoring muscle mass or function to weak or dystrophic muscle in the adult.  
     [0757] This gene also shows highly brain preferential expression. The CG50273-01 gene encodes a novel transmembrane protein. The combination of brain and skeletal muscle-preferential expression is consistent with a protein present in cholinergic synapses. Indeed, this gene shows homology to the cholinergic receptor CHRNA4 subunit. Therefore, this gene may be useful in the treatment of multiple sclerosis, ALS, or any disease in which the cholinergic system has been implicated (Alzheimer&#39;s disease).  
     [0758] Low but significant levels of expression are seen in renal and ovarian cancer cell lines. Thus, expression of this gene could potentially be used to differentiate between these samples and other samples on this panel or as a marker to detect the presence of these cancers.  
     [0759] Panel 2D Summary: Ag2556  
     [0760] Highest expression of the CG50273-01 gene is seen in normal kidney (CT=28.4). Furthermore, this gene appears to be more highly expressed in normal kidney tissue adjacent to a kidney cancer, than in the cancer itself. Thus, expression of this gene could potentially be used as a marker to differentiate between normal and cancerous kidney tissue. Moreover, therapeutic modulation of the expression or function of this gene could potentially be useful in the treatment of kidney cancer.  
     [0761] Panel 3D Summary: Ag2556  
     [0762] Expression of the CG50273-01 gene is restricted to a few cell lines on this panel including two lung cancer cell lines, medulloblastoma, two renal and three pancreatic cancer cell lines as well as the cerebellum samples which reflect the brain expression seen in Panel 1.3D.  
     [0763] Panel 4D Summary: Ag2556  
     [0764] The CG50273-01 gene appears to be preferentially expressed in normal thymus (CT=32.1). Since the thymus is involved in the development of the immune system, the transcript encoded by this gene could be used for detection of thymus/thymic cells as well as play a role in the homeostasis of the tissue and/or thymic/immune cells.  
     [0765] Panel CNS — 1 Summary: Ag2556  
     [0766] The widespread expression of the CG50273-01 gene in this panel confirms that it is expressed in the brain. Please see Panel 1.3D for discussion of potential utility of this gene in the central nervous system.  
     [0767] NOV4 (CG50289-01: Serine Protease)  
     [0768] Expression of gene CG50289-01 was assessed using the primer-probe sets Ag3600, Ag792 and Ag2555, described in Tables DA, DB and DC. Results of the RTQ-PCR runs are shown in Tables DD, DE, and DF.  
               TABLE DA                          Probe Name Ag3600                                         Start       Primers   Sequences   Length   Position                                         Forward   5′-agccaagcagcagtgactac-3′   (SEQ ID NO:148)   20   507               Probe   TET-5′-accatccacgaggacatgctgtg-3′-TAMRA   (SEQ ID NO:149)   23   527               Reverse   5′-aaatggcctttcctgttatgag-3′   (SEQ ID NO:150)   22   560                  
 
     [0769]               TABLE DB                          Probe Name Ag792                                         Start       Primers   Sequences   Length   Position                                         Forward   5′-agccaagcagcagtgactac-3′   (SEQ ID NO:151)   20   507               Probe   TET-5′-accatccacgaggacatgctgtg-3′-TAMRA   (SEQ ID NO:152)   23   527               Reverse   5′-aaatggcctttcctgttatgag-3′   (SEQ ID NO:153)   22   560                    
     [0770]               TABLE DC                          Probe Name Ag2555                                         Start       Primers   Sequences   Length   Position                                         Forward   5′-ctcataacaggaaaggccattt-3′   (SEQ ID NO:154)   22   560               Probe   TET-5′-agactccaggggtcccctcgtct-3′-TAMRA   (SEQ ID NO:155)   23   589               Reverse   5′-aggaaccaggtgccatttaat-3′   (SEQ ID NO:156)   21   616                    
     [0771]               TABLE DD                          General_screening_panel_v1.4                                 Rel. Exp. (%) Ag3600,       Rel. Exp. (%) Ag3600,       Tissue Name   Run 217676536   Tissue Name   Run 217676536                                     Adipose   0.0   Renal ca. TK-10   0.0       Melanoma*   0.0   Bladder   1.2       Hs688(A).T       Melanoma*   0.0   Gastric ca. (liver met.)   0.0       Hs688(B).T       NCI-N87       Melanoma* M14   0.0   Gastric ca. KATO III   0.0       Melanoma*   0.0   Colon ca. SW-948   0.0       LOXIMVI       Melanoma* SK-   0.0   Colon ca. SW480   0.0       MEL-5       Squamous cell   0.0   Colon ca.* (SW480   0.0       carcinoma SCC-4       met) SW620       Testis Pool   100.0   Colon ca. HT29   0.0       Prostate ca.*   1.3   Colon ca. HCT-116   0.0       (bonemet) PC-3       Prostate Pool   0.0   Colon ca. CaCo-2   3.7       Placenta   0.0   Colon cancer tissue   0.0       Uterus Pool   0.0   Colon ca. SW1116   0.0       Ovarian ca. OVCAR-3   0.0   Colon ca. Colo-205   0.0       Ovarian ca. SK-OV-3   0.0   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   1.3   Colon Pool   2.6       Ovarian ca. OVCAR-5   0.0   Small Intestine Pool   0.6       Ovarian ca. IGROV-1   0.0   Stomach Pool   4.0       Ovarian ca. OVCAR-8   0.0   Bone Marrow Pool   3.0       Ovary   0.0   Fetal Heart   0.0       Breast ca. MCF-7   0.0   Heart Pool   0.4       Breast ca. MDA-   0.0   Lymph Node Pool   2.5       MB-231       Breast ca. BT 549   0.0   Fetal Skeletal Muscle   0.0       Breast ca. T47D   0.0   Skeletal Muscle Pool   0.0       Breast ca. MDA-N   1.7   Spleen Pool   0.0       Breast Pool   1.3   Thymus Pool   2.6       Trachea   0.0   CNS cancer (glio/astro)   0.0               U87-MG       Lung   0.0   CNS cancer (glio/astro)   0.0               U-118-MG       Fetal Lung   0.0   CNS cancer (neuro;met)   0.0               SK-N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro) SF-   0.0               539       Lung ca. LX-1   0.0   CNS cancer (astro)   0.0               SNB-75       Lung ca. NCI-H146   0.0   CNS cancer (glio) SNB-   0.0               19       Lung ca. SHP-77   2.4   CNS cancer (glio) SF-   0.0               295       Lung ca. A549   0.0   Brain (Amygdala) Pool   0.0       Lung ca. NCI-H526   0.0   Brain (cerebellum)   0.0       Lung ca. NCI-H23   0.0   Brain (fetal)   0.0       Lung ca. NCI-H460   0.0   Brain (Hippocampus)   0.0               Pool       Lung ca. HOP-62   0.0   Cerebral Cortex Pool   0.0       Lung ca. NCI-H522   0.0   Brain (Substantia nigra)   0.0               Pool       Liver   0.0   Brain (Thalamus) Pool   0.0       Fetal Liver   0.0   Brain (whole)   0.0       Liver ca. HepG2   0.0   Spinal Cord Pool   0.0       Kidney Pool   1.3   Adrenal Gland   0.0       Fetal Kidney   1.3   Pituitary gland Pool   0.0       Renal ca. 786-0   0.0   Salivary Gland   0.0       Renal ca. A498   0.0   Thyroid (female)   0.0       Renal ca. ACHN   1.2   Pancreatic ca. CAPAN2   0.0       Renal ca. UO-31   0.0   Pancreas Pool   1.8                    
     [0772]               TABLE DE                          Panel 1.2                                 Rel. Exp. (%) Ag792,       Rel. Exp. (%) Ag792,       Tissue Name   Run 118335897   Tissue Name   Run 118335897                                     Endothelial cells   0.0   Renal ca. 786-0   0.0       Heart (Fetal)   0.0   Renal ca. A498   0.2       Pancreas   2.4   Renal ca. RXF 393   0.0       Pancreatic ca. CAPAN2   0.0   Renal ca. ACHN   0.0       Adrenal gland   0.0   Renal ca. UO-31   0.1       Thyroid   0.0   Renal ca. TK-10   0.0       Salivary gland   0.1   Liver   0.2       Pituitary gland   0.0   Liver (fetal)   0.1       Brain (fetal)   0.0   Liver ca. (hepatoblast)   0.0               HepG2       Brain (whole)   0.0   Lung   0.1       Brain (amygdala)   0.0   Lung (fetal)   0.0       Brain (cerebellum)   0.0   Lung ca. (small cell)   0.0               LX-1       Brain (hippocampus)   0.0   Lung ca. (small cell)   2.3               NCI-H69       Brain (thalamus)   0.0   Lung ca. (s.cell var.)   0.2               SHP-77       Cerebral Cortex   0.0   Lung ca. (large   0.1               cell)NCI-H460       Spinal cord   0.0   Lung ca. (non-sm.   1.0               cell) A549       glio/astro U87-MG   0.0   Lung ca. (non-s.cell)   0.0               NCI-H23       glio/astro U-118-MG   0.0   Lung ca. (non-s.cell)   0.2               HOP-62       astrocytoma SW1783   0.0   Lung ca. (non-s.cl)   0.0               NCI-H522       neuro*; met SK-N-AS   0.0   Lung ca. (squam.) SW   0.1               900       astrocytoma SF-539   0.0   Lung ca. (squam.)   1.2               NCI-H596       astrocytoma SNB-75   0.0   Mammary gland   0.0       glioma SNB-19   0.3   Breast ca.* (pl.ef)   0.0               MCF-7       glioma U251   0.0   Breast ca.* (pl.ef)   0.0               MDA-MB-231       glioma SF-295   0.0   Breast ca.* (pl. ef)   0.8               T47D       Heart   0.0   Breast ca. BT-549   0.2       Skeletal muscle   0.0   Breast ca. MDA-N   0.2       Bone marrow   0.0   Ovary   0.0       Thymus   0.0   Ovarian ca. OVCAR-3   0.0       Spleen   0.5   Ovarian ca. OVCAR-4   0.0       Lymph node   0.0   Ovarian ca. OVCAR-5   2.7       Colorectal   0.0   Ovarian ca. OVCAR-8   0.0       Stomach   0.1   Ovarian ca. IGROV-1   0.3       Small intestine   0.0   Ovarian ca. (ascites)   0.0               SK-OV-3       Colon ca. SW480   0.0   Uterus   0.0       Colon ca.* SW620   0.0   Placenta   0.0       (SW480 met)       Colon ca. HT29   0.1   Prostate   0.1       Colon ca. HCT-116   0.0   Prostate ca.* (bone   0.0               met) PC-3       Colon ca. CaCo-2   0.0   Testis   100.0       CC Well to Mod Diff   0.7   Melanoma   0.0       (ODO3866)       Hs688(A).T       Colon ca. HCC-2998   0.0   Melanoma* (met)   0.2               Hs688(B).T       Gastric ca. (liver met)   0.2   Melanoma UACC-62   0.0       NCI-N87       Bladder   2.0   Melanoma M14   1.6       Trachea   0.0   Melanoma LOX IMVI   0.0       Kidney   0.0   Melanoma* (met) SK-   0.0               MEL-5       Kidney (fetal)   0.0                    
     [0773]               TABLE DF                          Panel 1.3D                                         Rel. Exp. (%)   Rel. Exp. (%)       Rel. Exp. (%)   Rel. Exp. (%)           Ag2555, Run   Ag792, Run       Ag2555, Run   Ag792, Run       Tissue Name   162292287   165693644   Tissue Name   162292287   165693644                                             Liver   0.0   0.0   Kidney (fetal)   0.0   0.0       adenocarcinoma       Pancreas   0.0   0.0   Renal ca. 786-0   0.0   0.0       Pancreatic ca.   0.0   0.0   Renal ca. A498   0.0   0.0       CAPAN 2       Adrenal gland   0.0   0.0   Renal ca. RXF   0.0   0.0                   393       Thyroid   0.0   0.0   Renal ca.   0.0   0.0                   ACHN       Salivary gland   0.0   0.0   Renal ca. UO-   0.0   0.0                   31       Pituitary gland   0.0   0.0   Renal ca. TK-   0.0   0.0                   10       Brain (fetal)   0.0   0.0   Liver   0.0   0.0       Brain (whole)   0.0   0.0   Liver (fetal)   0.0   0.0       Brain (amygdala)   0.0   0.0   Liver ca.   0.0   0.0                   (hepatoblast)                   HepG2       Brain   0.0   0.0   Lung   0.0   0.0       (cerebellum)       Brain   0.0   0.0   Lung (fetal)   0.0   0.0       (hippocampus)       Brain (substantia   0.0   0.0   Lung ca. (small   0.0   0.0       nigra)           cell) LX-1       Brain (thalamus)   0.0   0.0   Lung ca. (small   0.0   0.0                   cell) NCI-H69       Cerebral Cortex   0.0   0.0   Lung ca. (s.cell   0.0   0.0                   var.) SHP-77       Spinal cord   0.0   0.0   Lung ca. (large   0.0   0.0                   cell)NCI-H460       glio/astro U87-   0.0   0.0   Lung ca. (non-   0.0   4.5       MG           sm. cell) A549       glio/astro U-118-   0.0   0.0   Lung ca. (non-   0.0   0.0       MG           s.cell) NCI-                   H23       astrocytoma   0.0   0.0   Lung ca. (non-   0.0   0.0       SW1783           s.cell) HOP-62       neuro*; met SK-   0.0   0.0   Lung ca. (non-   0.0   0.0       N-AS           s.cl) NCI-H522       astrocytoma SF-   0.0   2.4   Lung ca.   0.0   0.0       539           (squam.) SW                   900       astrocytoma SNB-   0.0   0.0   Lung ca.   0.0   0.0       75           (squam.) NCI-                   H596       glioma SNB-19   0.0   0.0   Mammary   0.0   0.0                   gland       glioma U251   0.0   2.5   Breast ca.*   0.0   0.0                   (pl.ef) MCF-7       glioma SF-295   0.0   0.0   Breast ca.*   0.0   0.0                   (pl.ef) MDA-                   MB-231       Heart (Fetal)   0.0   0.0   Breast ca.* (pl.   0.0   0.0                   ef) T47D       Heart   0.0   0.0   Breast ca. BT-   0.0   0.0                   549       Skeletal muscle   0.0   4.2   Breast ca.   0.0   0.0       (Fetal)           MDA-N       Skeletal muscle   0.0   0.0   Ovary   0.0   0.0       Bone marrow   0.0   1.9   Ovarian ca.   0.0   2.0                   OVCAR-3       Thymus   0.0   0.0   Ovarian ca.   0.0   0.0                   OVCAR-4       Spleen   0.0   0.0   Ovarian ca.   0.0   0.0                   OVCAR-5       Lymph node   0.0   0.0   Ovarian ca.   0.0   0.0                   OVCAR-8       Colorectal   0.0   3.4   Ovarian ca.   0.0   0.0                   IGROV-1       Stomach   0.0   3.7   Ovarian ca.   0.0   0.0                   (ascites) SK-                   OV-3       Small intestine   0.0   2.2   Uterus   0.0   0.0       Colon ca. SW480   0.0   0.0   Placenta   0.0   0.0       Colon ca.*   0.0   0.0   Prostate   0.0   0.0       SW620 (SW480       met)       Colon ca. HT29   0.0   0.0   Prostate ca.*   0.0   0.0                   (bone met) PC-3       Colon ca. HCT-   0.0   0.0   Testis   100.0   100.0       116       Colon ca. CaCo-2   0.0   0.0   Melanoma   0.0   0.0                   Hs688(A).T       CC Well to Mod   0.0   0.0   Melanoma*   0.0   0.0       Diff (ODO3866)           (met)                   Hs688(B).T       Colon ca. HCC-   0.0   0.0   Melanoma   0.0   0.0       2998           UACC-62       Gastric ca. (liver   0.0   0.0   Melanoma   0.0   4.0       met) NCI-N87           M14       Bladder   0.0   1.0   Melanoma   0.0   0.0                   LOX IMVI       Trachea   0.0   0.0   Melanoma*   0.0   0.0                   (met) SK-                   MEL-5       Kidney   0.0   0.0   Adipose   0.0   0.0                    
     [0774] CNS_Neurodegeneration_v1.0 Summary: Ag3600  
     [0775] Expression of the CG50289-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     [0776] General_Screening_Panel_v1.4 Summary: Ag3600  
     [0777] Expression of the CG50289-01 gene is exclusive to the testis (CT=31.8). This gene encodes a serine protease homolog. Serine proteases are important in many aspects of cellular physiology including post-translational processing, protein degradation and cellular signalling. The exclusive expression of this gene in the testis suggests that the protein encoded by this gene may be an excellent target for modulating male reproduction.  
     [0778] Panel 1.2 Summary: Ag792  
     [0779] Highest expression of the CG50289-01 gene is seen in the testis (CT=27.5), a result that is concordant with the results in General_screening_panel_v1.4. Low but significant expression is also seen in the pancreas. This expression profile suggests that the protein encoded by this gene may be an excellent target for modulation of male reproduction and/or hormone release from the pancreas.  
     [0780] Panel 1.3D Summary: Ag792/Ag2555  
     [0781] Two experiments with the same probe and primer set show expression of the CG50289-01 gene to be exclusive to the testis (CTs=32-33). This result is in excellent agreement with the results from Panel 1.2 and General_screening_panel_v1.4. Thus, this exclusive expression of this gene in the testis suggests that the protein encoded by this gene may be an excellent target for modulating male reproduction.  
     [0782] Panel 2D Summary: Ag2555  
     [0783] Expression of the CG50289-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     [0784] Panel 4.1D Summary: Ag3600  
     [0785] Expression of the CG50289-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     [0786] Panel 4D Summary: Ag2555  
     [0787] Expression of the CG50289-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     [0788] NOV5a (CG50353-01: Wnt7a-like)  
     [0789] Expression of gene CG50353-01 was assessed using the primer-probe set Ag3093, described in Table EA. Results of the RTQ-PCR runs are shown in Tables EB, and EC.  
               TABLE EA                          Probe Name Ag3093                                         Start       Primers   Sequences   Length   Position                                         Forward   5′-ctgtgacctcatgtgctgtg-3′   (SEQ ID NO:157)   20   909               Probe   TET-5′-gtggctacaacacccaccagtacgc-3′-TAMRA   (SEQ ID NO:158)   25   932               Reverse   5′-acatagcagcaccagtggaa-3′   (SEQ ID NO:159)   20   982                  
 
     [0790]               TABLE EB                          Panel 1.3D                                 Rel. Exp. (%) Ag3093,       Rel. Exp. (%) Ag3093,       Tissue Name   Run 167985246   Tissue Name   Run 167985246                                     Liver adenocarcinoma   2.8   Kidney (fetal)   0.1       Pancreas   0.0   Renal ca. 786-0   0.2       Pancreatic ca. CAPAN 2   1.7   Renal ca. A498   0.0       Adrenal gland   0.0   Renal ca. RXF 393   0.4       Thyroid   0.0   Renal ca. ACHN   0.0       Salivary gland   0.0   Renal ca. UO-31   0.5       Pituitary gland   0.0   Renal ca. TK-10   0.0       Brain (fetal)   3.6   Liver   0.0       Brain (whole)   1.5   Liver (fetal)   0.0       Brain (amygdala)   1.8   Liver ca.   0.0               (hepatoblast) HepG2       Brain (cerebellum)   0.9   Lung   0.2       Brain (hippocampus)   1.4   Lung (fetal)   0.9       Brain (substantia nigra)   0.9   Lung ca. (small cell)   0.0               LX-1       Brain (thalamus)   0.0   Lung ca. (small cell)   0.2               NCI-H69       Cerebral Cortex   3.5   Lung ca. (s.cell var.)   0.0               SHP-77       Spinal cord   0.6   Lung ca. (large   0.0               cell)NCI-H460       glio/astro U87-MG   0.6   Lung ca. (non-sm.   0.2               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)   0.0               NCI-H522       astrocytoma SF-539   0.2   Lung ca. (squam.)   0.0               SW 900       astrocytoma SNB-75   0.1   Lung ca. (squam.)   0.3               NCI-H596       glioma SNB-19   0.0   Mammary gland   0.0       glioma U251   0.0   Breast ca.* (pl.ef)   0.2               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   0.0       Skeletal muscle (Fetal)   0.0   Breast ca. MDA-N   0.0       Skeletal muscle   0.0   Ovary   0.0       Bone marrow   0.0   Ovarian ca. OVCAR-3   0.1       Thymus   0.0   Ovarian ca. OVCAR-4   37.1       Spleen   0.3   Ovarian ca. OVCAR-5   0.7       Lymph node   0.0   Ovarian ca. OVCAR-8   0.0       Colorectal   0.0   Ovarian ca. IGROV-1   6.8       Stomach   0.0   Ovarian ca. (ascites)   100.0               SK-OV-3       Small intestine   0.0   Uterus   0.0       Colon ca. SW480   0.4   Placenta   0.0       Colon ca.* SW620   1.4   Prostate   0.0       (SW480 met)       Colon ca. HT29   0.0   Prostate ca.* (bone   2.0               met) PC-3       Colon ca. HCT-116   0.0   Testis   0.3       Colon ca. CaCo-2   0.2   Melanoma   0.0               Hs688(A).T       CC Well to Mod Diff   0.0   Melanoma* (met)   0.0       (ODO3866)       Hs688(B).T       Colon ca. HCC-2998   0.1   Melanoma UACC-62   0.0       Gastric ca. (liver met)   0.5   Melanoma M14   0.0       NCI-N87       Bladder   0.0   Melanoma LOX   0.0               IMVI       Trachea   0.1   Melanoma* (met)   0.0               SK-MEL-5       Kidney   0.0   Adipose   0.2                    
     [0791]               TABLE EC                          Panel 4D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag3093, Run       Ag3093, Run       Tissue Name   164392077   Tissue Name   164392077                                     Secondary Th1 act   0.0   HUVEC IL-1beta   0.0       Secondary Th2 act   0.0   HUVEC IFN gamma   0.0       Secondary Tr1 act   0.0   HUVEC TNF alpha + IFN   0.0               gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha + IL4   0.0       Secondary Th2 rest   0.0   HUVEC IL-11   0.0       Secondary Tr1 rest   0.0   Lung Microvascular EC   0.0               none       Primary Th1 act   0.0   Lung Microvascular EC   0.0               TNFalpha + IL-1beta       Primary Th2 act   0.0   Microvascular Dermal EC   0.0               none       PrimaryTr1 act   0.0   Microsvasular Dermal EC   0.0               TNFalpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   57.4               TNFalpha + IL 1beta       Primary Th2 rest   0.0   Small airway epithelium   17.7               none       Primary Tr1 rest   0.0   Small airway epithelium   100.0               TNFalpha + IL-1beta       CD45RA CD4   0.0   Coronery artery SMC rest   0.0       lymphocyte act       CD45RO CD4   0.0   Coronery artery SMC   0.0       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   0.0       Secondary CD8   0.0   Astrocytes TNFalpha + IL-   0.0       lymphocyte rest       1beta       Secondary CD8   0.0   KU-812 (Basophil) rest   0.0       lymphocyte act       CD4 lymphocyte none   4.9   KU-812 (Basophil)   1.2               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.0   CCD1106 (Keratinocytes)   47.6       CD95 CH11       none       LAK cells rest   0.0   CCD1106 (Keratinocytes)   33.7               TNFalpha + IL-1beta       LAK cells IL-2   0 0   Liver cirrhosis   1.4       LAK cells IL-2 + IL-12   0.0   Lupus kidney   0.0       LAK cells IL-2 + IFN   0.0   NCI-H292 none   4.1       gamma       LAK cells IL-2 + IL-18   0.0   NCI-H292 IL-4   4.8       LAK cells   0.0   NCI-H292 IL-9   1.8       PMA/ionomycin       NK Cells IL-2 rest   0.0   NCI-H292 IL-13   2.5       Two Way MLR 3 day   0.0   NCI-H292 IFN gamma   1.6       Two Way MLR 5 day   0.0   HPAEC none   0.0       Two Way MLR 7 day   0.0   HPAEC TNF alpha + IL-   0.0               1beta       PBMC rest   3.5   Lung fibroblast none   0.0       PBMC PWM   0.8   Lung fibroblast TNF alpha +   0.0               IL-1beta       PBMC PHA-L   0.0   Lung fibroblast IL-4   0.0       Ramos (B cell) none   0.0   Lung fibroblast IL-9   0.0       Ramos (B cell)   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   0.0   Dermal fibroblast   0.0               CCD1070 TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast   0.0       PMA/ionomycin       CCD1070 IL-1beta       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   0.0   IBD Crohn&#39;s   0.0       Monocytes LPS   0.0   Colon   1.0       Macrophages rest   0.0   Lung   2.0       Macrophages LPS   0.0   Thymus   0.0       HUVEC none   0.0   Kidney   0.0       HUVEC starved   0.0                    
     [0792] Panel 1.3D Summary: Ag3093  
     [0793] The CG50353-01 gene is expressed exclusively in two ovarian cancer cell lines, with highest expression in the SK-OV-3 cell line (CT=30.28). This cell line is unusual because it is derived from ascites. Thus, this gene could potentially be used as a marker for ovarian cancer, particularly ascites derived cancer or as a marker for ascites. Furthermore, antibodies or small molecule drugs could potentially be used in a therapeutic manner to modulate the activity of this gene in ovarian cancer.  
     [0794] Panel 2.2 Summary: Ag3093  
     [0795] Expression of the CG50353-01 gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0796] Panel 4D Summary: Ag3093  
     [0797] The CG50353-01 gene is expressed at the highest level in TNF alpha+IL-1 beta treated small airway epithelial cells (CT=32.6) as well as TNF alpha+IL-1 beta treated bronchial epithelial cells and CCD1106 keratinocytes (treated and non-treated). The presence of this transcript in keratinocytes suggests that this gene may be important in skin disorders including psoriasis. Expression in airway/bronchial cell types suggests that this gene may also be involved in inflammatory lung disorders that include chronic obstructive pulmonary disease, asthma, allergy and emphysema. Therefore, therapeutic modalities that involve this gene or gene product may be beneficial in the treatment of these conditions.  
     [0798] NOV6a (CG50221-01: Apical Endosomal Glycoprotein)  
     [0799] Expression of gene CG5022 1-01 was assessed using the primer-probe sets Ag2495 and Ag4806, described in Tables FA and FB. Results of the RTQ-PCR runs are shown in Table FC.  
               TABLE FA                          Probe Name Ag2495                                         Start       Primers   Sequences   Length   Position                                         Forward   5′-ctggcacccctgctatactc-3′   (SEQ ID NO:160)   20   1003               Probe   TET-5′-attccaagcctcaggcacctccaact-3′-TAMRA   (SEQ ID NO:161)   26   1034               Reverse   5′-tgatagaagaccagccatctca-3′   (SEQ ID NO:162)   22   1066                  
 
     [0800]               TABLE FB                          Probe Name Ag4806                                         Start       Primers   Sequences   Length   Position                                         Forward   5′-ctacgtggctctggatgatct-3′   (SEQ ID NO:163)   21   2909               Probe   TET-5′-cctgccctcagccaggttcctgt-3′-TAMRA   (SEQ ID NO:164)   23   2947               Reverse   5′-acacaggccagactcaaaatc-3′   (SEQ ID NO:165)   21   2970                    
     [0801]               TABLE FC                          General_screening_panel_v1.4                                 Rel. Exp. (%) Ag4806,       Rel. Exp. (%) Ag4806,       Tissue Name   Run 223204110   Tissue Name   Run 223204110                                     Adipose   7.6   Renal ca. TK-10   4.4       Melanoma*   4.6   Bladder   13.7       Hs688(A).T       Melanoma*   12.7   Gastric ca. (liver met.)   6.6       Hs688(B).T       NCI-N87       Melanoma* M14   27.7   Gastric ca. KATO III   0.0       Melanoma*   0.0   Colon ca. SW-948   7.7       LOXIMVI       Melanoma* SK-   0.0   Colon ca. SW480   9.6       MEL-5       Squamous cell   0.0   Colon ca.* (SW480   7.2       carcinoma SCC-4       met) SW620       Testis Pool   0.0   Colon ca. HT29   15.0       Prostate ca.* (bone   0.0   Colon ca. HCT-116   15.2       met) PC-3       Prostate Pool   3.6   Colon ca. CaCo-2   12.5       Placenta   4.7   Colon cancer tissue   15.8       Uterus Pool   0.0   Colon ca.SW1116   16.8       Ovarian ca. OVCAR-3   0.3   Colon ca. Colo-205   13.9       Ovarian ca. SK-OV-3   19.9   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   0.0   Colon Pool   0.0       Ovarian ca. OVCAR-5   14.2   Small Intestine Pool   0.0       Ovarian ca. IGROV-1   24.1   Stomach Pool   1.3       Ovarian ca. OVCAR-8   23.2   Bone Marrow Pool   0.0       Ovary   0.7   Fetal Heart   17.0       Breast ca. MCF-7   6.7   Heart Pool   4.2       Breast ca. MDA-   65.1   Lymph Node Pool   3.5       MB-231       Breast ca. BT 549   18.8   Fetal Skeletal Muscle   6.5       Breast ca. T47D   100.0   Skeletal Muscle Pool   11.8       Breast ca. MDA-N   8.7   Spleen Pool   18.7       Breast Pool   1.9   Thymus Pool   12.9       Trachea   0.0   CNS cancer (glio/astro)   25.9               U87-MG       Lung   0.0   CNS cancer (glio/astro)   37.9               U-118-MG       Fetal Lung   19.9   CNS cancer (neuro; met)   9.3               SK-N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro) SF-   3.2               539       Lung ca. LX-1   11.0   CNS cancer (astro)   33.4               SNB-75       Lung ca. NCI-H146   0.0   CNS cancer (glio) SNB-   11.0               19       Lung ca. SHP-77   11.4   CNS cancer (glio) SF-   9.8               295       Lung ca. A549   33.7   Brain (Amygdala) Pool   9.0       Lung ca. NCI-H526   0.0   Brain (cerebellum)   22.4       Lung ca. NCI-H23   7.0   Brain (fetal)   14.4       Lung ca. NCI-H460   9.7   Brain (Hippocampus)   8.4               Pool       Lung ca. HOP-62   7.9   Cerebral Cortex Pool   0.0       Lung ca. NCI-H522   0.0   Brain (Substantia nigra)   18.9               Pool       Liver   40.1   Brain (Thalamus) Pool   8.2       Fetal Liver   5.1   Brain (whole)   3.5       Liver ca. HepG2   16.6   Spinal Cord Pool   7.8       Kidney Pool   11.5   Adrenal Gland   4.0       Fetal Kidney   16.7   Pituitary gland Pool   13.9       Renal ca. 786-0   25.7   Salivary Gland   0.8       Renal ca. A498   0.0   Thyroid (female)   1.8       Renal ca. ACHN   0.0   Pancreatic ca. CAPAN2   0.5       Renal ca. UO-31   8.8   Pancreas Pool   11.7                    
     [0802] CNS_Neurodegeneration_v1.0 Summary: Ag2495  
     [0803] Expression of the CG50221-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     [0804] General_Screening_Panel_v1.4 Summary: Ag4806  
     [0805] Expression of the CG50221-01 gene is highest in a breast cancer cell line (CT=31.5). This gene is also expressed in breast, ovarian and colon cancer cell lines at higher levels when compared to normal tissue samples. Hence, expression of this gene might be used as a marker to identify normal tissue from cancerous tissue in these organs.  
     [0806] There is relatively low level of expression in most endocrine (metabolic)-related tissues except for liver. Modulation of this gene or gene-product may therefore be beneficial in treating various abnormalities related to liver function. The higher levels of expression in adult liver (CT=32.7) when compared to fetal liver suggest that expression of this gene can also be used to differentiate fetal vs adult liver tissue. Conversely, higher levels of expression in fetal lung (CT=33) when compared to adult lung (CT=40) suggest involvement of this gene in the development of the lung. Expression of this gene could also therefore be used to differentiate between fetal and adult lung tissue.  
     [0807] Panel 1.3D Summary: Ag2495  
     [0808] Expression of the CG50221-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     [0809] Panel 2D Summary: Ag2495  
     [0810] Expression of the CG50221-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     [0811] Panel 4D Summary: Ag2495  
     [0812] Expression of the CG5022 1-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     [0813] NOV7a (CG50367-01: ADAM13-like)  
     [0814] Expression of gene CG50367-01 was assessed using the primer-probe set Ag2425, described in Table GA. Results of the RTQ-PCR runs are shown in Tables GB, GC, and GD.  
               TABLE GA                          Probe Name Ag2425                                         Start       Primers   Sequences   Length   Position                                         Forward   5′-ggctcctgctgaccatattc-3′   (SEQ ID NO:166)   20   2342               Probe   TET-5′-catttaccctccaccatttctcccag-3′-TAMRA   (SEQ ID NO:167)   26   2366               Reverse   5′-gctgggctcatgagagttct-3′   (SEQ ID NO:168)   20   2398                  
 
     [0815]               TABLE GB                          Panel 1.3D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2425,       Ag2425,       Tissue Name   Run 155561580   Tissue Name   Run 155561580                                     Liver adenocarcinoma   0.0   Kidney (fetal)   3.9       Pancreas   1.8   Renal ca. 786-0   0.0       Pancreatic ca. CAPAN 2   0.0   Renal ca. A498   0.0       Adrenal gland   0.9   Renal ca. RXF 393   0.0       Thyroid   2.7   Renal ca. ACHN   1.6       Salivary gland   1.1   Renal ca. UO-31   0.0       Pituitary gland   0.5   Renal ca. TK-10   0.0       Brain (fetal)   4.6   Liver   0.0       Brain (whole)   2.3   Liver (fetal)   1.2       Brain (amygdala)   4.2   Liver ca.   0.0               (hepatoblast) HepG2       Brain (cerebellum)   0.0   Lung   2.8       Brain (hippocampus)   25.3   Lung (fetal)   17.9       Brain (substantia nigra)   2.4   Lung ca. (small cell)   0.0               LX-1       Brain (thalamus)   9.4   Lung ca. (small cell)   0.0               NCI-H69       Cerebral Cortex   1.5   Lung ca. (s. cell var.)   1.0               SHP-77       Spinal cord   3.9   Lung ca. (large   0.0               cell) NCI-H460       glio/astro U87-MG   0.0   Lung ca. (non-sm.   1.7               cell) A549       glio/astro U-118-MG   1.1   Lung ca. (non-s. cell)   1.8               NCI-H23       astrocytoma SW1783   0.0   Lung ca. (non-s. cell)   0.0               HOP-62       neuro*; met SK-N-AS   0.0   Lung ca. (non-s. cl)   0.0               NCI-H522       astrocytoma SF-539   0.0   Lung ca. (squam.)   0.0               SW 900       astrocytoma SNB-75   0.0   Lung ca. (squam.)   0.0               NCI-H596       glioma SNB-19   0.8   Mammary gland   13.5       glioma U251   0.0   Breast ca.* (pl. ef)   0.0               MCF-7       glioma SF-295   0.0   Breast ca.* (pl. ef)   0.0               MDA-MB-231       Heart (Fetal)   3.4   Breast ca.* (pl. ef)   0.0               T47D       Heart   1.1   Breast ca. BT-549   1.6       Skeletal muscle (Fetal)   100.0   Breast ca. MDA-N   0.0       Skeletal muscle   0.9   Ovary   1.9       Bone marrow   3.3   Ovarian ca. OVCAR-3   0.0       Thymus   4.1   Ovarian ca. OVCAR-4   0.0       Spleen   2.7   Ovarian ca. OVCAR-5   0.0       Lymph node   4.6   Ovarian ca. OVCAR-8   0.0       Colorectal   5.9   Ovarian ca. IGROV-1   0.0       Stomach   7.3   Ovarian ca. (ascites)   0.0               SK-OV-3       Small intestine   18.4   Uterus   37.4       Colon ca. SW480   0.0   Placenta   1.8       Colon ca.* SW620   0.0   Prostate   8.8       (SW480 met)       Colon ca. HT29   0.0   Prostate ca.* (bone   0.0               met) PC-3       Colon ca. HCT-116   0.0   Testis   7.5       Colon ca. CaCo-2   0.0   Melanoma   5.0               Hs688(A).T       CC Well to Mod Diff   0.0   Melanoma* (met)   3.3       (ODO3866)       Hs688(B).T       Colon ca. HCC-2998   0.0   Melanoma UACC-62   0.0       Gastric ca. (liver met)   0.0   Melanoma M14   0.0       NCI-N87       Bladder   0.0   Melanoma LOX   0.0               IMVI       Trachea   15.8   Melanoma* (met)   0.0               SK-MEL-5       Kidney   1.8   Adipose   1.6                    
     [0816]               TABLE GC                          Panel 2D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2425, Run       Ag2425, Run       Tissue Name   155562155   Tissue Name   155562155                                     Normal Colon   100.0   Kidney Margin   0.0               8120608       CC Well to Mod Diff   5.6   Kidney Cancer   0.0       (ODO3866)       8120613       CC Margin (ODO3866)   4.5   Kidney Margin   2.1               8120614       CC Gr.2 rectosigmoid   20.7   Kidney Cancer   2.2       (ODO3868)       9010320       CC Margin (ODO3868)   21.9   Kidney Margin   6.1               9010321       CC Mod Diff (ODO3920)   6.7   Normal Uterus   49.3       CC Margin (ODO3920)   61.6   Uterine Cancer   92.7               064011       CC Gr.2 ascend colon   1.0   Normal Thyroid   18.3       (ODO3921)       CC Margin (ODO3921)   6.2   Thyroid Cancer   0.0       CC from Partial   0.0   Thyroid Cancer   2.8       Hepatectomy (ODO4309)       A302152       Mets       Liver Margin (ODO4309)   0.0   Thyroid Margin   20.4               A302153       Colon mets to lung   0.0   Normal Breast   53.2       (OD04451-01)       Lung Margin (OD04451-02)   0.0   Breast Cancer   0.0       Normal Prostate 6546-1   66.4   Breast Cancer   2.6               (OD04590-01)       Prostate Cancer   25.9   Breast Cancer Mets   11.5       (OD04410)       (OD04590-03)       Prostate Margin   72.7   Breast Cancer   0.0       (OD04410)       Metastasis       Prostate Cancer   45.4   Breast Cancer   24.7       (OD04720-01)       Prostate Margin   33.7   Breast Cancer   51.8       (OD04720-02)       Normal Lung   84.1   Breast Cancer   3.1               9100266       Lung Met to Muscle   9.4   Breast Margin   12.9       (ODO4286)       9100265       Muscle Margin   0.0   Breast Cancer   17.3       (ODO4286)       A209073       Lung Malignant Cancer   0.0   Breast Margin   99.3       (OD03126)       A2090734       Lung Margin (OD03126)   10.6   Normal Liver   0.0       Lung Cancer (OD04404)   0.0   Liver Cancer   4.0       Lung Margin (OD04404)   0.0   Liver Cancer 1025   4.9       Lung Cancer (OD04565)   13.7   Liver Cancer 1026   0.0       Lung Margin (OD04565)   10.6   Liver Cancer 6004-T   0.0       Lung Cancer (OD04237-   0.0   Liver Tissue 6004-N   8.5       01)       Lung Margin (OD04237-   0.0   Liver Cancer 6005-T   0.0       02)       Ocular Mel Met to Liver   0.0   Liver Tissue 6005-N   0.0       (ODO4310)       Liver Margin (ODO4310)   0.0   Normal Bladder   11.1       Melanoma Metastasis   0.0   Bladder Cancer   3.1       Lung Margin (OD04321)   2.9   Bladder Cancer   14.6       Normal Kidney   9.7   Bladder Cancer   2.4               (OD04718-01)       Kidney Ca, Nuclear grade 2   0.0   Bladder Normal   10.6       (OD04338)       Adjacent (OD04718-               03)       Kidney Margin   6.0   Normal Ovary   0.0       (OD04338)       Kidney Ca Nuclear grade   0.0   Ovarian Cancer   0.0       1/2 (OD04339)       Kidney Margin   0.0   Ovarian Cancer   3.2       (OD04339)       (OD04768-07)       Kidney Ca, Clear cell type   0.0   Ovary Margin   6.0       (OD04340)       (OD04768-08)       Kidney Margin   4.0   Normal Stomach   12.7       (OD04340)       Kidney Ca, Nuclear grade   0.0   Gastric Cancer   9.9       3 (OD04348)       9060358       Kidney Margin   6.7   Stomach Margin   0.0       (OD04348)       9060359       Kidney Cancer   0.0   Gastric Cancer   39.2       (OD04622-01)       9060395       Kidney Margin   7.4   Stomach Margin   26.4       (OD04622-03)       9060394       Kidney Cancer   0.0   Gastric Cancer   6.2       (OD04450-01)       9060397       Kidney Margin   0.0   Stomach Margin   3.3       (OD04450-03)       9060396       Kidney Cancer 8120607   0.0   Gastric Cancer 064005   25.3                    
     [0817]               TABLE GD                          Panel 4D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2425, Run       Ag2425, Run       Tissue Name   155562267   Tissue Name   155562267                                     Secondary Th1 act   0.0   HUVEC IL-1beta   0.0       Secondary Th2 act   0.0   HUVEC IFN gamma   0.0       Secondary Tr1 act   0.0   HUVEC TNF alpha + IFN   0.0               gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha + IL4   0.0       Secondary Th2 rest   0.0   HUVEC IL-11   0.0       Secondary Tr1 rest   0.0   Lung Microvascular EC   0.0               none       Primary Th1 act   0.0   Lung Microvascular EC   0.0               TNF alpha + IL-1beta       Primary Th2 act   0.0   Microvascular Dermal EC   0.0               none       Primary Tr1 act   1.3   Microsvasular Dermal EC   0.0               TNF alpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   0.0               TNF alpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium   0.0               none       Primary Tr1 rest   0.0   Small airway epithelium   0.0               TNF alpha + IL-1beta       CD45RA CD4   1.8   Coronery artery SMC rest   0.0       lymphocyte act       CD45RO CD4   1.4   Coronery artery SMC   0.0       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   0.0       Secondary CD8   0.0   Astrocytes TNF alpha + IL-   0.0       lymphocyte rest       1beta       Secondary CD8   0.0   KU-812 (Basophil) rest   0.0       lymphocyte act       CD4 lymphocyte none   1.3   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   3.9   CCD1106 (Keratinocytes)   0.0       CD95 CH11       none       LAK cells rest   0.0   CCD1106 (Keratinocytes)   0.0               TNF alpha + IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   4.9       LAK cells IL-2 + IL-12   0.0   Lupus kidney   0.0       LAK cells IL-2 + IFN   0.0   NCI-H292 none   0.0       gamma       LAK cells IL-2 + IL-18   0.0   NCI-H292 IL-4   0.0       LAK cells   0.0   NCI-H292 IL-9   0.0       PMA/ionomycin       NK Cells IL-2 rest   0.0   NCI-H292 IL-13   0.0       Two Way MLR 3 day   0.0   NCI-H292 IFN gamma   0.0       Two Way MLR 5 day   0.0   HPAEC none   0.0       Two Way MLR 7 day   0.0   HPAEC TNF alpha +   0.0               IL-1beta       PBMC rest   0.0   Lung fibroblast none   13.0       PBMC PWM   0.0   Lung fibroblast TNF alpha +   2.7               IL-1beta       PBMC PHA-L   0.0   Lung fibroblast IL-4   3.4       Ramos (B cell) none   0.0   Lung fibroblast IL-9   10.7       Ramos (B cell)   0.0   Lung fibroblast IL-13   5.9       ionomycin       B lymphocytes PWM   0.0   Lung fibroblast IFN   3.3               gamma       B lymphocytes CD40L   0.0   Dermal fibroblast   23.7       and IL-4       CCD1070 rest       EOL-1 dbcAMP   0.0   Dermal fibroblast   5.6               CCD1070 TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast   12.5       PMA/ionomycin       CCD1070 IL-1beta       Dendritic cells none   0.0   Dermal fibroblast IFN   64.6               gamma       Dendritic cells LPS   0.0   Dermal fibroblast IL-4   100.0       Dendritic cells anti-   0.0   IBD Colitis 2   0.0       CD40       Monocytes rest   0.0   IBD Crohn&#39;s   0.0       Monocytes LPS   0.0   Colon   28.3       Macrophages rest   0.0   Lung   21.6       Macrophages LPS   0.0   Thymus   0.0       HUVEC none   0.0   Kidney   0.0       HUVEC starved   0.0                    
     [0818] CNS_Neurodegeneration_v1.0 Summary: Ag2425  
     [0819] Expression of the CG50367-01 gene is low/undetectable in all samples on this panel (CT&gt;34.5).  
     [0820] Panel 1.3D Summary: Ag2425  
     [0821] Highest expression of the CG50367-01 gene is seen in fetal skeletal muscle (CT=31.1). This gene appears to be more highly expressed in fetal skeletal muscle when compared to expression in adult skeletal muscle (CT=40). Thus expression of this gene could be used to differentiate between fetal and adult skeletal muscle. Furthermore, the higher levels of expression in the fetal source of the tissue suggest that the protein encoded by this gene may be involved in the development of the skeletal muscle in the fetus. Thus, therapeutic modulation of the expression or function of this gene may restore muscle mass or function to weak or dystrophic muscle in the adult.  
     [0822] This gene is expressed at a very low level in all the cancer cell lines used in this panel. The absence of expression of this gene in the cancer cell lines suggests that modulation of the function of the gene product through the use of peptides, polypeptides, chimeric molecules or small molecule drugs, may be useful in the therapy of cancer.  
     [0823] This gene is a cell-surface metalloprotease expressed at low levels in the hippocampus. It may be useful in the treatment of diseases in which the hippocampus is involved, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, bipolar disorder, or temporal lobe epilepsy.  
     [0824] Panel 2D Summary: Ag2425  
     [0825] The CG50367-01 gene is expressed at low levels in this panel, with highest expression in the colon (CT=32.2). Moderately higher levels of expression are seen in normal breast, uterine and thyroid tissues compared to the adjacent cancers. Hence, expression of this gene might be used as a marker to identify normal tissue from cancerous tissue in these organs. Therapeutic modulation of the activity of the product of this gene, through the use of peptides, polypeptides, chimeric molecules or small molecule drugs, may be useful in the therapy of these cancers.  
     [0826] Panel 4D Summary: Ag2425  
     [0827] The CG50367-01 transcript is most highly expressed in dermal fibroblast upon treatment with either Il-4 or Ifn gamma (CTs=31-32) and at lower levels in resting dermal fibroblasts. This transcript is also expressed in lung fibroblasts and normal lung and thymus. This transcript encodes for a ADAM like protein, a member of membrane-anchored glycoproteins that have been implicated in diverse cellular processes from cell cell interaction to shedding of cell surface proteases. The expression of this transcript in dermal and lung fibroblasts suggests that the protein encoded by this transcript might be involved in disease associated with fibrosis or fibroplasia. Modulation of the expression or the function of this molecule might be useful for the treatment of psoriasis, chronic obstructive pulmonary diseases and potentially for osteoarthritis and rheumatoid arthritis.  
     [0828] NOV8 (CG50321-01: Leucine Rich Containing F Box Protein)  
     [0829] Expression of gene CG50321-01 was assessed using the primer-probe set Ag2557, described in Table HA. Results of the RTQ-PCR runs are shown in Tables HB, HC and HD.  
               TABLE HA                          Probe Name Ag2557                                         Start       Primers   Sequences   Length   Position                                         Forward   5′-tgactttgaacttgcagacttg-3′   (SEQ ID NO:169)   22   646               Probe   TET-5′-cttgcaaatcacagatgaaggtctca-3′-TAMRA   (SEQ ID NO:170)   26   668               Reverse   5′-aggcacaaagggattgtaactt-3′   (SEQ ID NO:171)   22   717                  
 
     [0830]               TABLE HB                          CNS_neurodegeneration_v1.0                                 Rel. Exp.                   (%)       Rel. Exp. (%)           Ag2557,       Ag2557,           Run       Run       Tissue Name   206974725   Tissue Name   206974725                                     AD 1 Hippo   14.9   Control (Path) 3   6.7               Temporal Ctx       AD 2 Hippo   27.4   Control (Path) 4   24.8               Temporal Ctx       AD 3 Hippo   6.1   AD 1 Occipital Ctx   12.5       AD 4 Hippo   4.9   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   92.7   AD 3 Occipital Ctx   5.0       AD 6 Hippo   49.0   AD 4 Occipital Ctx   16.7       Control 2 Hippo   28.5   AD 5 Occipital Ctx   15.6       Control 4 Hippo   8.4   AD 5 Occipital Ctx   48.0       Control (Path) 3   6.9   Control 1 Occipital   3.6       Hippo       Ctx       AD 1 Temporal Ctx   15.8   Control 2 Occipital   71.2               Ctx       AD 2 Temporal Ctx   29.9   Control 3 Occipital   12.4               Ctx       AD 3 Temporal Ctx   3.8   Control 4 Occipital   5.7               Ctx       AD 4 Temporal Ctx   18.7   Control (Path) 1   100.0               Occipital Ctx       AD 5 Inf Temporal   92.7   Control (Path) 2   8.4       Ctx       Occipital Ctx       AD 5 Sup Temporal   32.1   Control (Path) 3   2.1       Ctx       Occipital Ctx       AD 6 Inf Temporal   36.9   Control (Path) 4   8.4       Ctx       Occipital Ctx       AD 6 Sup Temporal   37.1   Control 1 Parietal   7.2       Ctx       Ctx       Control 1 Temporal   6.6   Control 2 Parietal   33.7       Ctx       Ctx       Control 2 Temporal   51.1   Control 3 Parietal   17.7       Ctx       Ctx       Control 3 Temporal   13.2   Control (Path) 1   95.3       Ctx       Parietal Ctx       Control 3 Temporal   6.8   Control (Path) 2   17.6       Ctx       Parietal Ctx       Control (Path) 1   66.0   Control (Path) 3   5.1       Temporal Ctx       Parietal Ctx       Control (Path) 2   29.3   Control (Path) 4   39.8       Temporal Ctx       Parietal Ctx                    
     [0831]               TABLE HC                          Panel 1.3D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2557,       Ag2557,       Tissue Name   Run 165640108   Tissue Name   Run 165640108                                     Liver adenocarcinoma   23.8   Kidney (fetal)   12.7       Pancreas   5.4   Renal ca. 786-0   5.9       Pancreatic ca. CAPAN 2   20.7   Renal ca. A498   21.0       Adrenal gland   12.2   Renal ca. RXF 393   13.5       Thyroid   5.8   Renal ca. ACHN   10.5       Salivary gland   7.2   Renal ca. UO-31   6.3       Pituitary gland   8.5   Renal ca. TK-10   23.2       Brain (fetal)   31.4   Liver   4.0       Brain (whole)   55.1   Liver (fetal)   13.1       Brain (amygdala)   43.5   Liver ca.   7.5               (hepatoblast) HepG2       Brain (cerebellum)   44.8   Lung   7.7       Brain (hippocampus)   42.3   Lung (fetal)   12.4       Brain (substantia nigra)   14.8   Lung ca. (small cell)   12.2               LX-1       Brain (thalamus)   30.6   Lung ca. (small cell)   14.2               NCI-H69       Cerebral Cortex   18.7   Lung ca. (s. cell var.)   15.4               SHP-77       Spinal cord   11.2   Lung ca. (large   54.0               cell) NCI-H460       glio/astro U87-MG   15.9   Lung ca. (non-sm.   42.3               cell) A549       glio/astro U-118-MG   22.4   Lung ca. (non-s. cell)   17.3               NCI-H23       astrocytoma SW1783   24.7   Lung ca. (non-s. cell)   32.1               HOP-62       neuro*; met SK-N-AS   16.4   Lung ca. (non-s. cl)   14.2               NCI-H522       astrocytoma SF-539   6.3   Lung ca. (squam.)   8.6               SW 900       astrocytoma SNB-75   18.7   Lung ca. (squam.)   10.7               NCI-H596       glioma SNB-19   22.7   Mammary gland   15.8       glioma U251   32.1   Breast ca.* (pl. ef)   9.3               MCF-7       glioma SF-295   30.4   Breast ca.* (pl. ef)   16.3               MDA-MB-231       Heart (Fetal)   3.7   Breast ca.* (pl. ef)   24.5               T47D       Heart   7.9   Breast ca. BT-549   12.6       Skeletal muscle (Fetal)   2.3   Breast ca. MDA-N   4.4       Skeletal muscle   15.7   Ovary   5.8       Bone marrow   10.8   Ovarian ca. OVCAR-3   10.4       Thymus   14.6   Ovarian ca. OVCAR-4   6.2       Spleen   15.1   Ovarian ca. OVCAR-5   15.5       Lymph node   21.3   Ovarian ca. OVCAR-8   3.3       Colorectal   8.1   Ovarian ca. IGROV-1   2.7       Stomach   15.7   Ovarian ca. (ascites)   28.9               SK-OV-3       Small intestine   20.9   Uterus   22.4       Colon ca. SW480   10.2   Placenta   8.5       Colon ca.* SW620   6.7   Prostate   6.8       (SW480 met)       Colon ca. HT29   1.0   Prostate ca.* (bone   17.6               met) PC-3       Colon ca. HCT-116   10.7   Testis   27.0       Colon ca. CaCo-2   9.0   Melanoma   4.2               Hs688(A).T       CC Well to Mod Diff   7.7   Melanoma* (met)   5.9       (ODO3866)       Hs688(B).T       Colon ca. HCC-2998   7.7   Melanoma UACC-62   9.7       Gastric ca. (liver met)   100.0   Melanoma M14   36.1       NCI-N87       Bladder   14.9   Melanoma LOX   2.2               IMVI       Trachea   9.9   Melanoma* (met)   4.1               SK-MEL-5       Kidney   3.5   Adipose   7.4                    
     [0832]               TABLE HD                          Panel 4D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2557, Run       Ag2557, Run       Tissue Name   164393419   Tissue Name   164393419                                     Secondary Th1 act   27.4   HUVEC IL-1beta   4.8       Secondary Th2 act   19.8   HUVEC IFN gamma   19.8       Secondary Tr1 act   28.7   HUVEC TNF alpha + IFN   3.9               gamma       Secondary Th1 rest   11.4   HUVEC TNF alpha + IL4   6.9       Secondary Th2 rest   17.9   HUVEC IL-11   8.0       Secondary Tr1 rest   19.3   Lung Microvascular EC   19.5               none       Primary Th1 act   26.8   Lung Microvascular EC   13.7               TNF alpha + IL-1beta       Primary Th2 act   23.5   Microvascular Dermal EC   35.6               none       Primary Tr1 act   36.9   Microsvasular Dermal EC   12.2               TNF alpha + IL-1beta       Primary Th1 rest   75.8   Bronchial epithelium   29.9               TNF alpha + IL1beta       Primary Th2 rest   43.8   Small airway epithelium   17.2               none       Primary Tr1 rest   34.2   Small airway epithelium   47.6               TNF alpha + IL-1beta       CD45RA CD4   16.6   Coronery artery SMC rest   19.9       lymphocyte act       CD45RO CD4   36.3   Coronery artery SMC   17.2       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   23.3   Astrocytes rest   21.8       Secondary CD8   22.1   Astrocytes TNF alpha + IL-   21.5       lymphocyte rest       1beta       Secondary CD8   17.4   KU-812 (Basophil) rest   16.2       lymphocyte act       CD4 lymphocyte none   15.9   KU-812 (Basophil)   56.6               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   36.6   CCD1106 (Keratinocytes)   14.6       CD95 CH11       none       LAK cells rest   21.5   CCD1106 (Keratinocytes)   6.0               TNF alpha + IL-1beta       LAK cells IL-2   33.9   Liver cirrhosis   3.9       LAK cells IL-2 + IL-12   23.2   Lupus kidney   3.9       LAK cells IL-2 + IFN   33.0   NCI-H292 none   46.3       gamma       LAK cells IL-2 + IL-18   35.4   NCI-H292 IL-4   57.8       LAK cells   8.7   NCI-H292 IL-9   47.0       PMA/ionomycin       NK Cells IL-2 rest   23.3   NCI-H292 IL-13   28.5       Two Way MLR 3 day   20.3   NCI-H292 IFN gamma   24.3       Two Way MLR 5 day   16.7   HPAEC none   18.3       Two Way MLR 7 day   10.7   HPAEC TNF alpha + IL-1   12.8               beta       PBMC rest   26.6   Lung fibroblast none   12.8       PBMC PWM   85.3   Lung fibroblast TNF alpha +   16.5               IL-1beta       PBMC PHA-L   43.5   Lung fibroblast IL-4   13.6       Ramos (B cell) none   15.1   Lung fibroblast IL-9   13.7       Ramos (B cell)   92.7   Lung fibroblast IL-13   9.6       ionomycin       B lymphocytes PWM   93.3   Lung fibroblast IFN   11.2               gamma       B lymphocytes CD40L   39.5   Dermal fibroblast   21.9       and IL-4       CCD1070 rest       EOL-1 dbcAMP   65.5   Dermal fibroblast   52.9               CCD1070 TNF alpha       EOL-1 dbcAMP   58.2   Dermal fibroblast   19.5       PMA/ionomycin       CCD1070 IL-1beta       Dendritic cells none   18.9   Dermal fibroblast IFN   13.8               gamma       Dendritic cells LPS   17.7   Dermal fibroblast IL-4   23.0       Dendritic cells anti-   23.7   IBD Colitis 2   1.3       CD40       Monocytes rest   33.9   IBD Crohn&#39;s   2.8       Monocytes LPS   46.7   Colon   39.2       Macrophages rest   42.6   Lung   22.4       Macrophages LPS   26.6   Thymus   47.0       HUVEC none   12.9   Kidney   100.0       HUVEC starved   37.6                    
     [0833] CNS_Neurodegeneration_v1.0 Summary: Ag2557  
     [0834] A small decrease is detected in the expression of the CG5032 1-01 gene in the postmortem brains of Alzheimer&#39;s patients when compared normal controls. This protein is an F-Box protein containing leucine-rich repeats; these proteins are involved in ubiquitination and proteosomal degradation of proteins. This gene is therefore an excellent drug target for the treatment of diseases involving protein precipitation including Alzheimer&#39;s disease, Huntington&#39;s disease, Parkinson&#39;s disease, progressive supranuclear palsy, or spinocerebellar ataxia.  
     [0835] Reference:  
     [0836] Ilyin G P, Rialland M, Pigeon C, Guguen-Guillouzo C. cDNA cloning and expression analysis of new members of the mammalian F-box protein family. Genomics Jul. 1, 2000;67(1):40-7  
     [0837] F-box proteins are critical components of the SCF ubiquitin-protein ligase complex and are involved in substrate recognition and recruitment for ubiquitination and consequent degradation by the proteasome. We have isolated cDNAs encoding a further 10 mammalian F-box proteins. Five of them (FBL3 to FBL7) share structural similarities with Skp2 and contain C-terminal leucine-rich repeats. The other 5 proteins have different putative protein-protein interaction motifs. Specifically, FBS and FBWD4 proteins contain Sec7 and WD40-repeat domains, respectively. The C-terminal region of FBA shares similarity with bacterial protein ApaG while FBG2 shows homology with the F-box protein NFB42. The marked differences in F-box gene expression in human tissues suggest their distinct role in ubiquitin-dependent protein degradation.  
     [0838] Panel 1.3D Summary: Ag2557  
     [0839] The CG50321-01 gene is expressed at a moderate to low level in most of the cell lines and tissues on this panel, with highest expression in a gastric cancer cell line (CT=30.4). This ubiquitous expression suggests a role in cell prolferation and survival.  
     [0840] There is a broad range of expression of this gene in endocrine (metabolic)-related tissues including adrenal, brain, GI tract, liver and skeletal muscle. Targeting this gene and/or gene-product may aid in the treatment of any number of endocrine or metabolically-related diseases, including obesity and diabetes.  
     [0841] This panel demonstrates the expression of this gene in the CNS in an independent group of patients. See panel CNS_Neurodegeneration for a discussion of utility of this gene in the central nervous system.  
     [0842] Panel 4D Summary: Ag 2557  
     [0843] Highest expression of the CG50321-01 transcript is found in kidney (CT=29.1). High levels of expression are also detected in activated B cells (primary B cells and B cell lymphoma), effector Th1 and the eosinphili cell line (EOL-1). At lower levels this transcript is expressed in a wide range of cell types of significance in the immune response in health and disease. This transcrpit encodes for leucine rich protein with a F-box domain. F-box proteins have been described as components of ubiquitin-ligase complexes, in which they bind substrates for ubiquitin-mediated proteolysis. It is therefore theorized that they participate in the regulation of many processes, including cell division, transcription, signal transduction and development (ref 1). Targeting this gene and/or gene-product by small molecules may aid in the treatment of diseases associated with T and B cell or eosinophil involvement and lead to improvement of the symptoms of patients suffering from autoimmune, inflammatory and atopic diseases such as asthma, allergies, inflammatory bowel diseases, lupus erythematosus, rheumatoid arthritis, psoriasis and atopic skin diseases.  
     [0844] Reference:  
     [0845] 1. Patton E E, Willems A R, Tyers M. Combinatorial control in ubiquitin-dependent proteolysis: don&#39;t Skp the F-box hypothesis.  
     [0846] Trends Genet June 1998;14(6):236-43  
     [0847] The ubiquitin-dependent proteolytic pathway targets many key regulatory proteins for rapid intracellular degradation. Specificity in protein ubiquitination derives from E3 ubiquitin protein ligases, which recognize substrate proteins. Recently, analysis of the E3s that regulate cell division has revealed common themes in structure and function. One particularly versatile class of E3s, referred to as Skp1p-Cdc53p-F-box protein (SCF) complexes, utilizes substrate-specific adaptor subunits called F-box proteins to recruit various substrates to a core ubiquitination complex. A vast array of F-box proteins have been revealed by genome sequencing projects, and the early returns from genetic analysis in several organisms promise that F-box proteins will participate in the regulation of many processes, including cell division, transcription, signal transduction and development.  
     [0848] NOV9 (CG55902-01/AC079907.6: Steroid Binding Protein)  
     [0849] Expression of gene CG55902-01 was assessed using the primer-probe set Ag2626, described in Table JA. Please note that results from Panels 1.3D, 2.2 and 4D have been filed previously.  
                   TABLE JA                          Probe Name Ag2626                                                 Start           Primers   Sequences   Length   Position                                             Forward   5′-ttctcaatgagtttggcagc-3′   (SEQ ID NO:172)   20   365                   Probe   TET-5′-aacctggacttcaaggctgaagacca-3′-TAMRA    (SEQ ID NO:173)   26   388               Reverse   5′-aaacctcagaacccctcctt-3′   (SEQ ID NO:174)   20   430                  
 
     [0850]               TABLE JB                       CNS_neurodegeneration_v1.0                                            CNS_neurodegeneration_v1.0 Summary: Ag2626           Expression of the CG55902-01 gene is low/undetectable           in all samples on this panel (CT &gt; 34.5).           NOV10a and NOV10b (CG50307-01 and CG50307-02:           Steroid Dehydogenase-like)                        
     [0851] Expression of gene CG50307-01 and variant CG50307-02 was assessed using the primer-probe sets Ag2248 and Ag2548, described in Tables KA and KB. Results of the RTQ-PCR runs are shown in Tables KC, KD, KE, KF, KG, KH, KI and KJ.  
                   TABLE KA                          Probe Name Ag2248                                                 Start           Primers   Sequences   Length   Position                                             Forward   5′-agcctacgctgaagagttagc-3′   (SEQ ID NO:175)   21   425                   Probe   TET-5′-aagccgaggtctcaatataatcctga-3′-TMARA    (SEQ ID NO:176)   26   446               Reverse   5′-acctgcaacttctcctcgtt-3′   (SEQ ID NO:177)   20   480                  
 
     [0852]                   TABLE KB                          Probe Name Ag2548                                                 Start           Primers   Sequences   Length   Position                                             Forward   5′-gacgttggcatcttggtaaata-3′   (SEQ ID NO:178)   22   612                   Probe   TET-5′-cgcagtatttcactcagctgtccgag-3′-TAMRA    (SEQ ID NO:179)   26   658               Reverse   5′-ttatgatgtcccagagcttgtc-3′   (SEQ ID NO:180)   22   684                    
     [0853]               TABLE KC                          CNS_neurodegeneration_v1.0                                         Rel. Exp. (%)   Rel. Exp. (%)       Rel. Exp. (%)   Rel. Exp. (%)           Ag2248, Run   Ag2548, Run       Ag2248, Run   Ag2548, Run       Tissue Name   207928610   208300028   Tissue Name   207928610   208300028                                             AD 1 Hippo   20.2   14.7   Control   4.4   4.1                   (Path) 3                   Temporal                   Ctx       AD 2 Hippo   27.2   46.7   Control   37.6   37.9                   (Path) 4                   Temporal                   Ctx       AD 3 Hippo   5.6   6.9   AD 1   11.0   20.0                   Occipital Ctx       AD 4 Hippo   10.8   11.4   AD 2   0.0   0.0                   Occipital Ctx                   (Missing)       AD 5 Hippo   85.3   2.6   AD 3   6.1   6.2                   Occipital Ctx       AD 6 Hippo   69.7   50.0   AD 4   21.6   22.7                   Occipital Ctx       Control 2   42.9   45.7   AD 5   14.0   11.8       Hippo           Occipital Ctx       Control 4   11.3   12.5   AD 5   47.3   49.0       Hippo           Occipital Ctx       Control   7.6   7.2   Control 1   1.4   1.8       (Path) 3           Occipital Ctx       Hippo       AD 1   18.2   20.4   Control 2   81.8   83.5       Temporal           Occipital Ctx       Ctx       AD 2   27.4   42.6   Control 3   13.1   15.9       Temporal           Occipital Ctx       Ctx       AD 3   5.5   6.8   Control 4   6.7   6.5       Temporal           Occipital Ctx       Ctx       AD 4   17.4   22.5   Control   91.4   100.0       Temporal           (Path) 1       Ctx           Occipital Ctx       AD 5 Inf   89.5   99.3   Control   11.8   9.7       Temporal           (Path) 2       Ctx           Occipital Ctx       AD 5 Sup   34.6   50.7   Control   1.6   2.0       Temporal           (Path) 3       Ctx           Occipital Ctx       AD 6 Inf   42.9   42.0   Control   15.5   15.1       Temporal           (Path) 4       Ctx           Occipital Ctx       AD 6 Sup   50.3   45.1   Control 1   8.1   4.6       Temporal           Parietal Ctx       Ctx       Control 1   3.7   3.5   Control 2   30.1   33.4       Temporal           Parietal Ctx       Ctx       Control 2   56.6   42.6   Control 3   24.0   21.9       Temporal           Parietal Ctx       Ctx       Control 3   19.1   12.3   Control   100.0   84.7       Temporal           (Path) 1       Ctx           Parietal Ctx       Control 3   7.1   8.0   Control   26.8   20.3       Temporal           (Path) 2       Ctx           Parietal Ctx       Control   64.2   74.2   Control   4.7   3.7       (Path) 1           (Path) 3       Temporal           Parietal Ctx       Ctx       Control   23.5   30.1   Control   44.4   66.4       (Path) 2           (Path) 4       Temporal           Parietal Ctx       Ctx                    
     [0854]               TABLE KD                          Panel 1.3D                                         Rel. Exp. (%)   Rel. Exp. (%)       Rel. Exp. (%)   Rel. Exp. (%)           Ag2248, Run   Ag2548, Run       Ag2248, Run   Ag2548, Run       Tissue Name   159035206   162292266   Tissue Name   159035206   162292266                                             Liver   8.7   25.5   Kidney (fetal)   5.0   14.1       adenocarcinoma       Pancreas   1.1   1.7   Renal ca. 7860   5.3   7.5       Pancreatic Ca.   2.2   6.3   Renal ca. A498   10.2   9.0       CAPAN 2       Adrenal gland   6.6   6.0   Renal ca. RXF   1.5   9.0                   393       Thyroid   9.0   19.3   Renal ca. ACHN   1.7   12.8       Salivary gland   2.9   3.7   Renal ca. UO31   5.4   15.1       Pituitary gland   19.8   16.2   Renal ca. TK10   1.5   6.7       Brain (fetal)   28.3   14.3   Liver   1.3   0.4       Brain (whole)   22.7   25.2   Liver (fetal)   3.1   2.3       Brain (amygdala)   24.7   24.3   Liver ca.   8.1   18.7                   (hepatoblast)                   HepG2       Brain   11.6   14.6   Lung   10.2   7.4       (cerebellum)       Brain   100.0   45.1   Lung (fetal)   9.5   12.5       (hippocampus)       Brain (substantia   5.1   7.2   Lung ca. (small   11.0   16.0       nigra)           cell) LX-1       Brain (thalamus)   19.2   25.2   Lung ca. (small   7.5   6.3                   cell) NCI-H69       Cerebral Cortex   44.8   100.0   Lung ca. (s. cell   42.9   73.7                   var.) SHP-77       Spinal cord   4.8   14.9   Lung ca. (large   2.7   10.1                   cell) NCI-H460       glio/astro U87MG   11.7   42.3   Lung ca. (non-   1.8   4.1                   sm. cell) A549       glio/astro U-118-   20.7   12.0   Lung Ca. (non-   11.7   28.5       MG           s. cell) NCI-H23       astrocytoma   8.1   38.2   Lung ca. (non-   5.3   24.0       SW1783           s. cell) HOP-62       neuro*; met SK-   14.2   6.5   Lung ca. (non-   5.0   15.1       N-AS           s. cl) NCI-H522       astrocytoma SF-   3.9   15.2   Lung ca. (squam.)   3.4   12.6       539           SW 900       astrocytoma SNB-   8.8   11.3   Lung ca. (squam.)   1.5   1.9       75           NCI-H596       glioma SNB-19   4.1   20.0   Mammary   7.5   9.6                   gland       glioma U251   2.5   5.8   Breast ca.*   25.3   88.9                   (pl. ef) MCF-7       glioma SF-295   3.4   24.0   Breast ca.*   21.8   6.4                   (pl. ef) MDA-                   MB-231       Heart (Fetal)   9.7   35.1   Breast ca.* (pl.   13.6   29.3                   ef) T47D       Heart   3.6   11.4   Breast ca. BT-   22.1   7.4                   549       Skeletal muscle   8.2   44.1   Breast ca.   5.7   11.1       (Fetal)           MDA-N       Skeletal muscle   5.6   47.6   Ovary   5.4   26.6       Bone marrow   3.2   1.7   Ovarian ca.   2.5   4.8                   OVCAR-3       Thymus   3.5   40.6   Ovarian ca.   0.6   3.6                   OVCAR-4       Spleen   5.4   10.9   Ovarian ca.   3.8   13.1                   OVCAR-5       Lymph node   2.8   4.4   Ovarian Ca.   5.9   21.2                   OVCAR-8       Colorectal   1.9   9.4   Ovarian ca.   1.4   3.1                   IGROV-1       Stomach   2.2   2.7   Ovarian ca   5.3   13.1                   (ascites) SK-                   OV-3       Small intestine   5.0   7.3   Uterus   3.9   6.0       Colon ca. SW480   6.0   12.6   Placenta   5.2   8.8       Colon ca.*   4.7   11.1   Prostate   2.0   6.7       SW620 (SW480       met)       Colon ca. HT29   2.6   7.1   Prostate ca.*   5.4   9.7                   (bone met) PC-3       Colon ca. HCT-   9.5   22.4   Testis   7.7   24.8       116       Colon ca. CaCo-2   6.7   18.0   Melanoma   3.3   7.7                   Hs688(A).T       CC Well to Mod   4.8   13.2   Melanoma   1.2   6.9       Diff(ODO3866)           (met)                   Hs688(B).T       Colon ca. HCC-   17.2   10.2   Melanoma   1.5   5.6       2998           UACC-62       Gastric ca. (liver   10.8   14.7   Melanoma   4.3   8.1       met) NCI-N87           M14       Bladder   2.6   11.0   Melanoma   4.8   2.9                   LOX IMVI       Trachea   6.4   13.8   Melanoma*   6.9   10.4                   (met) SK-                   MEL-5       Kidney   1.7   14.1   Adipose   2.3   6.0                    
     [0855]               TABLE KB                          Panel 2D                                         Rel. Exp. (%)   Rel. Exp. (%)       Rel. Exp. (%)   Rel. Exp. (%)           Ag2248, Run   Ag2548, Run       Ag2248, Run   Ag2548, Run       Tissue Name   159035545   162326203   Tissue Name   159035545   162326203                                             Normal Colon   49.3   39.5   Kidney Margin   4.7   6.3                   8120608       CC Well to Mod   14.2   10.7   Kidney Cancer   7.1   14.0       Diff (ODO3866)           8120613       CC Margin   10.7   8.9   Kidney Margin   8.8   10.7       (ODO3866)           8120614       CC Gr.2   6.6   5.9   Kidney Cancer   10.9   13.7       rectosigmoid           9010320       (ODO3868)       CC Margin   5.8   6.9   Kidney Margin   9.7   18.4       (ODO3868)           9010321       CC Mod Diff   38.4   21.5   Normal Uterus   6.5   8.0       (0D03920)       CC Margin   14.5   9.5   Uterine Cancer   42.9   24.1       (ODO3920)           064011       CC Gr.2 ascend   25.5   15.8   Normal   40.3   31.0       colon           Thyroid       (ODO3921)       CC Margin   7.7   5.9   Thyroid   21.0   21.0       (ODO3921)           Cancer       CC from Partial   32.5   28.5   Thyroid   21.9   18.4       Hepatectomy           Cancer       (ODO4309) Mets           A302152       Liver Margin   12.2   9.0   Thyroid   37.9   39.0       (ODO4309)           Margin                   A302153       Colon mets to   15.6   8.5   Normal Breast   18.9   23.8       lung (OD04451-       01)       Lung Margin   12.6   9.2   Breast Cancer   14.2   20.2       (OD04451-02)       Normal Prostate   6.6   57.4   Breast Cancer   100.0   100.0       6546-1           (OD04590-01)       Prostate Cancer   40.3   31.0   Breast Cancer   87.1   90.1       (OD04410)           Mets                   (OD04590-03)       Prostate Margin   27.0   21.8   Breast Cancer   37.6   37.4       (OD04410)           Metastasis       Prostate Cancer   28.5   18.3   Breast Cancer   14.6   14.1       (OD04720-01)       Prostate Margin   35.8   25.0   Breast Cancer   27.4   28.9       (OD04720-02)       Normal Lung   56.6   39.0   Breast Cancer   46.7   41.5                   9100266       Lung Met to   33.4   22.7   Breast Margin   15.5   16.7       Muscle           9100265       (ODO4286)       Muscle Margin   22.1   12.3   Breast Cancer   42.3   42.9       (ODO4286)           A209073       Lung Malignant   33.4   27.0   Breast Margin   21.3   17.2       Cancer           A2090734       (OD03126)       Lung Margin   27.5   21.9   Normal Liver   5.4   4.6       (OD03126)       Lung Cancer   13.3   14.9   Liver Cancer   3.8   3.0       (OD04404)       Lung Margin   12.0   11.6   Liver Cancer   4.2   2.3       (OD04404)           1025       Lung Cancer   14.1   14.3   Liver Cancer   3.0   1.3       (OD04565)           1026       Lung Margin   6.9   11.0   Liver Cancer   3.6   1.6       (OD04565)           6004-T       Lung Cancer   95.9   82.4   Liver Tissue   11.7   9.0       (OD04237-01)           6004-N       Lung Margin   15.5   13.7   Liver Cancer   2.2   2.9       (OD04237-02)           6005-T       Ocular Mel Met   27.4   19.9   Liver Tissue   4.4   3.8       to Liver           6005-N       (ODO4310)       Liver Margin   5.1   3.4   Normal   26.6   16.0       (ODO4310)           Bladder       Melanoma   24.8   18.8   Bladder   5.0   3.0       Metastasis           Cancer       Lung Margin   23.8   20.0   Bladder   17.1   8.8       (OD04321)           Cancer       Normal Kidney   40.1   48.0   Bladder   22.2   15.5                   Cancer                   (OD04718-01)       Kidney Ca,   30.6   41.8   Bladder   21.2   15.6       Nuclear grade 2           Normal       (OD04338)           Adjacent                   (OD04718-03)       Kidney Margin   16.4   15.9   Normal Ovary   12.6   8.8       (OD04338)       Kidney Ca   11.3   15.8   Ovarian   21.6   16.5       Nuclear grade ½           Cancer       (OD04339)       Kidney Margin   19.6   24.5   Ovarian   40.1   33.9       (OD04339)           Cancer                   (OD04768-07)       Kidney Ca, Clear   20.4   30.8   Ovary Margin   11.3   4.0       cell type           (OD04768-08)       (OD04340)       Kidney Margin   18.4   13.9   Normal   12.2   8.8       (OD04348)           Stomach       Kidney Ca,   13.3   6.1   Gastric Cancer   5.0   3.0       Nuclear grade 3           9060358       (OD04348)       Kidney Margin   21.2   19.3   Stomach   16.0   11.0       (OD04348)           Margin                   9060359       Kidney Cancer   19.3   19.2   Gastric Cancer   16.3   12.6       (OD04622-01)           9060395       Kidney Margin   4.4   5.3   Stomach   13.9   10.6       (OD04622-03)           Margin                   9060394       Kidney Cancer   23.8   27.0   Gastric Cancer   24.0   12.1       (OD04450-01)           9060397       Kidney Margin   15.2   20.0   Stomach   6.4   7.1       (OD04450-03)           Margin                   9060396       Kidney Cancer   5.6   4.2   Gastric Cancer   37.1   20.3       8120607           064005                    
     [0856]               TABLE KF                          Panel 3D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2548, Run       Ag2548, Run       Tissue Name   164886193   Tissue Name   164886193                                     Daoy-Medulloblastoma   8.7   Ca Ski-Cervical epidermoid   10.6               carcinoma (metastasis)       TE671-Medulloblastoma   10.7   ES-2-Ovarian clear cell   11.3               carcinoma       D283 Med-   40.6   Ramos-Stimulated with   2.0       Medulloblastoma       PMA/ionomycin 6 h       PFSK-1-Primitive   9.0   Ramos-Stimulated with   8.8       Neuroectodermal       PMA/ionomycin 14 h       XF-498-CNS   9.3   MEG-01-Chronic   11.5               myelogenous leukemia               (megokaryoblast)       SNB-78-Glioma   12.9   Raji-Burkitt&#39;s lymphoma   4.5       SF-268-Glioblastoma   9.4   Daudi-Burkitt&#39;s lymphoma   12.0       T98G-Glioblastoma   13.7   U266-B-cell plasmacytoma   28.1       SK-N-SH-   14.9   CA46-Burkitt&#39;s lymphoma   9.2       Neuroblastoma       (metastasis)       SF-295-Glioblastoma   9.9   RL-non-Hodgkin&#39;s B-cell   2.2               lymphoma       Cerebellum   21.5   JM1-pre-B-cell lymphoma   6.3       Cerebellum   6.0   Jurkat-T cell leukemia   18.7       NCI-H292-   25.7   TF-1-Erythroleukemia   9.7       Mucoepidermoid lung       carcinoma       DMS-114-Small cell   16.3   HUT 78-T-cell lymphoma   17.1       lung cancer       DMS-79-Small cell lung   100.0   U937-Histiocytic lymphoma   11.2       cancer       NCI-H146-Small cell   20.9   KU-812-Myelogenous   5.3       lung cancer       leukemia       NCI-H526-Small cell   36.6   769-P-Clear cell renal   6.2       lung cancer       carcinoma       NCI-N417-Small cell   9.7   Caki-2-Clear cell renal   8.1       lung cancer       carcinoma       NCI-H82-Small cell lung   14.2   SW 839-Clear cell renal   2.9       cancer       carcinoma       NCI-H157-Squamous   19.6   G401-Wilms&#39; tumor   8.8       cell lung cancer       (metastasis)       NCI-H1155-Large cell   34.6   Hs766T-Pancreatic carcinoma   13.3       lung cancer       (LN metastasis)       NCI-H1299-Large cell   19.9   CAPAN-1-Pancreatic   7.7       lung cancer       adenocarcinoma (liver               metastasis)       NCI-H727-Lung   14.2   SU86.86-Pancreatic   10.0       carcinoid       carcinoma (liver metastasis)       NCI-UMC-11-Lung   12.6   BxPC-3-Pancreatic   4.3       carcinoid       adenocarcinoma       LX-1-Small cell lung   20.0   HPAC-Pancreatic   6.6       cancer       adenocarcinoma       Colo-205-Colon cancer   15.8   MIA PaCa-2-Pancreatic   4.6               carcinoma       KM12-Colon cancer   9.3   CFPAC-1-Pancreatic ductal   19.5               adenocarcinoma       KM20L2-Colon cancer   3.0   PANC-1-Pancreatic   9.5               epithelioid ductal carcinoma       NCI-H716-Colon cancer   19.1   T24-Bladder carcinma   9.9               (transitional cell)       SW-48-Colon   7.9   5637-Bladder carcinoma   4.7       adenocarcinoma       SW1116-Colon   7.4   HT-1197-Bladder carcinoma   6.1       adenocarcinoma       LS 174T-Colon   4.6   UM-UC-3-Bladder carcinma   2.8       adenocarcinoma       (transitional cell)       SW-948-Colon   1.1   A204-Rhabdomyosarcoma   3.4       adenocarcinoma       SW-480-Colon   2.7   HT-1080-Fibrosarcoma   10.7       adenocarcinoma       NCI-SNU-5-Gastric   9.3   MG-63-Osteosarcoma   1.3       carcinoma       KATO III-Gastric   24.0   SK-LMS-1-Leiomyosarcoma   9.5       carcinoma       (vulva)       NCI-SNU-16-Gastric   9.5   SJRH30-Rhabdomyosarcoma   10.2       carcinoma       (met to bone marrow)       NCI-SNU-1-Gastric   12.2   A431-Epidermoid carcinoma   5.0       carcinoma       RF-1-Gastric   5.1   WM266-4-Melanoma   10.5       adenocarcinoma       RF-48-Gastric   8.1   DU 145-Prostate carcinoma   0.0       adenocarcinoma       (brain metastasis)       MKN-45-Gastric   5.3   MDA-MB-468-Breast   20.7       carcinoma       adenocarcinoma       NCI-N87-Gastric   7.4   SCC-4-Squamous cell   0.0       carcinoma       carcinoma of tongue       OVCAR-5-Ovarian   2.7   SCC-9-Squamous cell   0.0       carcinoma       carcinoma of tongue       RL95-2-Uterine   3.8   SCC-15-Squamous cell   0.0       carcinoma       carcinoma of tongue       HelaS3-Cervical   10.7   CAL 27-Squamous cell   5.5       adenocarcinoma       carcinoma of tongue                    
     [0857]               TABLE KG                          Panel 4D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2248, Run       Ag2248, Run       Tissue Name   159034717   Tissue Name   159034717                                     Secondary Th1 act   27.2   HUVEC IL-1beta   8.4       Secondary Th2 act   33.4   HUVEC IFN gamma   14.4       Secondary Tr1 act   37.4   HUVEC TNF alpha + IFN   7.4               gamma       Secondary Th1 rest   11.7   HUVEC TNF alpha + IL4   6.6       Secondary Th2 rest   10.4   HUVEC IL-11   11.8       Secondary Tr1 rest   12.5   Lung Microvascular EC   9.9               none       Primary Th1 act   28.5   Lung Microvascular EC   18.2               TNF alpha + IL-1beta       Primary Th2 act   29.3   Microvascular Dermal EC   28.9               none       Primary Tr1 act   29.3   Microsvasular Dermal EC   20.2               TNF alpha + IL-1beta       Primary Th1 rest   62.4   Bronchial epithelium   20.7               TNF alpha + IL1beta       Primary Th2 rest   39.8   Small airway epithelium   6.9               none       Primary Tr1 rest   15.3   Small airway epithelium   40.3               TNF alpha + IL-1beta       CD45RA CD4   18.6   Coronery artery SMC rest   15.4       lymphocyte act       CD45RO CD4   20.9   Coronery artery SMC   6.8       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   14.7   Astrocytes rest   20.0       Secondary CD8   11.9   Astrocytes TNF alpha + IL-   15.8       lymphocyte rest       1beta       Secondary CD8   19.9   KU-812 (Basophil) rest   8.1       lymphocyte act       CD4 lymphocyte none   8.2   KU-812 (Basophil)   20.2               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   17.4   CCD1106 (Keratinocytes)   11.5       CD95 CH11       none       LAK cells rest   19.2   CCD1106 (Keratinocytes)   5.3               TNF alpha + IL-1beta       LAK cells IL-2   18.2   Liver cirrhosis   2.4       LAK cells IL-2 + IL-12   11.0   Lupus kidney   1.8       LAK cells IL-2 + IFN   19.5   NCI-H292 none   39.5       gamma       LAK cells IL-2 + IL-18   17.7   NCI-H292 IL-4   38.2       LAK cells   3.6   NCI-H292 IL-9   40.1       PMA/ionomycin       NK Cells IL-2 rest   11.0   NCI-H292 IL-13   18.2       Two Way MLR 3 day   19.2   NCI-H292 IFN gamma   14.7       Two Way MLR 5 day   8.9   HPAEC none   19.2       Two Way MLR 7 day   6.7   HPAEC TNF alpha +   28.5               IL-1beta       PBMC rest   5.8   Lung fibroblast none   17.4       PBMC PWM   40.6   Lung fibroblast TNF alpha +   17.1               IL-1beta       PBMC PHA-L   25.9   Lung fibroblast IL-4   30.4       Ramos (B cell) none   26.6   Lung fibroblast IL-9   20.2       Ramos (B cell)   100.0   Lung fibroblast IL-13   16.3       ionomycin       B lymphocytes PWM   35.6   Lung fibroblast IFN   28.1               gamma       B lymphocytes CD40L   29.7   Dermal fibroblast   32.3       and IL-4       CCD1070 rest       EOL-1 dbcAMP   10.5   Dermal fibroblast   57.0               CCD1070 TNF alpha       EOL-1 dbcAMP   7.5   Dermal fibroblast   15.3       PMA/ionomycin       CCD1070 IL-1beta       Dendritic cells none   11.6   Dermal fibroblast IFN   12.1               gamma       Dendritic cells LPS   7.7   Dermal fibroblast IL-4   20.3       Dendritic cells anti-   9.6   IBD Colitis 2   2.3       CD40       Monocytes rest   12.6   IBD Crohn&#39;s   2.6       Monocytes LPS   21.0   Colon   11.5       Macrophages rest   24.5   Lung   16.2       Macrophages LPS   14.8   Thymus   38.7       HUVEC none   25.9   Kidney   71.2       HUVEC starved   40.9                    
     [0858]               TABLE KH                          Panel 5 Islet                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2248, Run       Ag2248, Run       Tissue Name   233070521   Tissue Name   233070521                                     97457_Patient-   23.7   94709_Donor 2 AM - A_adipose   10.5       02go_adipose       97476_Patient-   12.3   94710_Donor 2 AM - B_adipose   5.0       07sk_skeletal muscle       97477_Patient-   18.9   94711_Donor 2 AM - C_adipose   5.3       07ut_uterus       97478_Patient-   35.6   94712_Donor 2 AD - A_adipose   14.5       07pl_placenta       99167_Bayer Patient 1   25.0   94713_Donor 2 AD - B_adipose   25.2       97482_Patient-   23.2   94714_Donor 2 AD - C_adipose   18.7       08ut_uterus       97483_Patient-   25.5   94742_Donor 3 U -   7.4       08pl_placenta       A_Mesenchymal Stem Cells       97486_Patient-   0.7   94743_Donor 3 U -   11.2       09sk_skeletal muscle       B_Mesenchymal Stem Cells       97487_Patient-   23.0   94730_Donor 3 AM - A_adipose   14.6       09ut_uterus       97488_Patient-   15.3   94731_Donor 3 AM - B_adipose   4.5       09pl_placenta       97492_Patient-   15.1   94732_Donor 3 AM - C_adipose   10.5       10ut_uterus       97493_Patient-   52.9   94733_Donor 3 AD - A_adipose   40.1       10pl_placenta       97495_Patient-   9.1   94734_Donor 3 AD - B_adipose   16.0       11go_adipose       97496_Patient-   10.2   94735_Donor 3 AD - C_adipose   14.0       11sk_skeletal muscle       97497_Patient-   21.8   77138_Liver_HepG2untreated   100.0       11ut_uterus       97498_Patient-   36.3   73556_Heart_Cardiac stromal cells   9.5       11pl_placenta       (primary)       97500_Patient-   21.0   81735_Small Intestine   8.7       12go_adipose       97501_Patient-   35.4   72409_Kidney_Proximal   16.7       12sk_skeletal muscle       Convoluted Tubule       97502_Patient-   15.5   82685_Small intestine_Duodenum   5.1       12ut_uterus       97503_Patient-   9.5   90650_Adrenal_Adrenocortical   18.0       12pl_placenta       adenoma       94721_Donor 2 U -   8.3   72410_Kidney_HRCE   42.0       A_Mesenchymal Stem       Cells       94722_Donor 2 U -   8.3   72411_Kidney_HRE   27.0       B_Mesenchymal Stem       Cells       94723_Donor 2 U -   20.4   73139_Uterus_Uterine smooth   41.5       C_Mesenchymal Stem       muscle cells       Cells                    
     [0859]               TABLE KI                          Panel 5D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2248, Run       Ag2248, Run       Tissue Name   166667616   Tissue Name   166667616                                     97457_Patient-   44.1   94709_Donor 2 AM - A_adipose   24.3       02go_adipose       97476_Patient-   13.6   94710_Donor 2 AM - B_adipose   7.0       07sk_skeletal muscle       97477_Patient-   42.0   94711_Donor 2 AM - C_adipose   3.1       07ut_uterus       97478_Patient-   64.6   94712_Donor 2 AD - A_adipose   13.9       07pl_placenta       97481_Patient-   29.7   94713_Donor 2 AD - B_adipose   39.2       08sk_skeletal muscle       97482_Patient-   19.5   94714_Donor 2 AD - C_adipose   35.4       08ut_uterus       97483_Patient-   42.0   94742_Donor 3 U -   17.2       08pl_placenta       A_Mesenchymal Stem Cells       97486_Patient-   7.3   94743_Donor 3 U -   6.4       09sk_skeletal muscle       B_Mesenchymal Stem Cells       97487_Patient-   26.2   94730_Donor 3 AM - A_adipose   10.0       09ut_uterus       97488_Patient-   31.0   94731_Donor 3 AM - B_adipose   6.5       09pl_placenta       97492_Patient-   30.4   94732_Donor 3 AM - C_adipose   7.6       10ut_uterus       97493_Patient-   100.0   94733_Donor 3 AD - A_adipose   19.5       10pl_placenta       97495_Patient-   13.1   94734_Donor 3 AD - B_adipose   25.3       11go_adipose       97496_Patient-   9.3   94735_Donor 3 AD - C_adipose   9.1       11sk_skeletal muscle       97497_Patient-   30.1   77138_Liver_HepG2untreated   51.1       11ut_uterus       97498_Patient-   25.0   73556_Heart_Cardiac stromal cells   4.1       11pl_placenta       (primary)       97500_Patient-   24.0   81735_Small Intestine   13.2       12go_adipose       97501_Patient-   70.7   72409_Kidney_Proximal   21.6       12sk_skeletal muscle       Convoluted Tubule       97502_Patient-   13.8   82685_Small intestine_Duodenum   3.7       12ut_uterus       97503_Patient-   8.5   90650_Adrenal_Adrenocortical   10.9       12pl_placenta       adenoma       94721_Donor 2 U -   12.4   72410_Kidney_HRCE   22.5       A_Mesenchymal Stem       Cells       94722_Donor 2 U -   19.9   72411_Kidney_HRE   25.3       B_Mesenchymal Stem       Cells       94723_Donor 2 U -   23.5   73139_Uterus_Uterine smooth   28.7       C_Mesenchymal Stem       muscle cells       Cells                    
     [0860]               TABLE KJ                          Panel CNS_1                                         Rel. Exp.           Rel. Exp. (%)       (%)           Ag2248,       Ag2248,           Run       Run       Tissue Name   171649039   Tissue Name   171649039                                     BA4 Control   39.8   BA17 PSP   29.1       BA4 Control2   41.8   BA17 PSP2   13.1       BA4   10.7   Sub Nigra Control   22.8       Alzheimer&#39;s2       BA4 Parkinson&#39;s   49.7   Sub Nigra Control2   42.6       BA4   100.0   Sub Nigra   15.1       Parkinson&#39;s2       Alzheimer&#39;s2       BA4   42.9   Sub Nigra   54.7       Huntington&#39;s       Parkinson&#39;s2       BA4   14.5   Sub Nigra   58.6       Huntington&#39;s2       Huntington&#39;s       BA4 PSP   4.4   Sub Nigra   48.6               Huntington&#39;s2       BA4 PSP2   20.0   Sub Nigra PSP2   5.1       BA4 Depression   11.7   Sub Nigra   8.7               Depression       BA4   7.0   Sub Nigra   11.4       Depression2       Depression2       BA7 Control   71.2   Glob Palladus   10.4               Control       BA7 Control2   30.4   Glob Palladus   5.9               Control2       BA7   9.2   Glob Palladus   13.8       Alzheimer&#39;s2       Alzheimer&#39;s       BA7 Parkinson&#39;s   17.7   Glob Palladus   2.7               Alzheimer&#39;s2       BA7   60.3   Glob Palladus   50.0       Parkinson&#39;s2       Parkinson&#39;s       BA7   44.8   Glob Palladus   10.7       Huntington&#39;s       Parkinson&#39;s2       BA7   49.0   Glob Palladus PSP   6.9       Huntington&#39;s2       BA7 PSP   34.4   Glob Palladus PSP2   7.2       BA7 PSP2   34.2   Glob Palladus   4.6               Depression       BA7 Depression   16.4   Temp Pole Control   14.6       BA9 Control   35.8   Temp Pole Control2   51.1       BA9 Control2   59.9   Temp Pole   7.7               Alzheimer&#39;s       BA9 Alzheimer&#39;s   4.0   Temp Pole   9.0               Alzheimer&#39;s2       BA9   20.0   Temp Pole   18.6       Alzheimer&#39;s2       Parkinson&#39;s       BA9 Parkinson&#39;s   36.6   Temp Pole   48.6               Parkinson&#39;s2       BA9   57.8   Temp Pole   44.4       Parkinson&#39;s2       Huntington&#39;s       BA9   57.8   Temp Pole PSP   2.6       Huntington&#39;s       BA9   24.1   Temp Pole PSP2   5.7       Huntington&#39;s2       BA9 PSP   12.5   Temp Pole   11.0               Depression2       BA9 PSP2   3.8   Cing Gyr Control   63.7       BA9 Depression   7.3   Cing Gyr Control2   37.4       BA9   18.6   Cing Gyr Alzheimer&#39;s   28.5       Depression2       BA17 Control   40.1   Cing Gyr   14.3               Alzheimer&#39;s2       BA17 Control2   35.1   Cing Gyr Parkinson&#39;s   32.8       BA17   6.8   Cing Gyr   55.1       Alzheimer&#39;s2       Parkinson&#39;s2       BA17   39.0   Cing Gyr   79.6       Parkinson&#39;s       Huntington&#39;s       BA17   51.1   Cing Gyr   19.2       Parkinson&#39;s2       Huntington&#39;s2       BA17   31.6   Cing Gyr PSP   14.2       Huntington&#39;s       BA17   20.2   Cing Gyr PSP2   10.8       Huntington&#39;s2       BA17   11.3   Cing Gyr Depression   4.8       Depression       BA17   29.5   Cing Gyr   19.3       Depression2       Depression2                    
     [0861] CNS_neurodegeneration_v1.0 Summary: Ag2248/Ag2548  
     [0862] Two experiments with two different probe and primer sets produce results that are in very good agreement, with highest expression of the CG50307-01 gene in the occipital and parietal cortex (CTs=27-29) of the brains of control patients. While this geen does not appear to be differentially expressed in Alzheimer&#39;s disease, these results confirm confirm the expression of this gene at moderate to high levels in the brains of an independent group of patients. Please see Panel 1.3d for discussion of utility in the central nervous system.  
     [0863] Panel 1.3D Summary: Ag2248/Ag2548  
     [0864] Two experiments with two different probe and primer sets show widespread expression of the CG50307-01 gene, with highest expression seen in regions of the brain (CTs=28-29).  
     [0865] This gene encodes a protein that is homologous to steroid dehydrogenase. Steroid treatment is used in a number of clinical conditions including Alzheimer&#39;s disease (estrogen), treatment of symptoms associated with menopause (estrogen), multiple sclerosis (glucocorticoids), and spinal cord injury (methylprednisolone). Treatment with an antagonst of this gene product, or reduction of the levels of this gene product could slow steroid degredation and lower the necessary amount given for therapeutic effect, thusreducing peripheral side effects.  
     [0866] This gene is moderately expressed in a variety of metabolic tissues including pancreas, adrenal, thyroid, pituitary, adult and fetal heart, adult and fetal skeletal muscle, fetal liver, and adipose. Thus, this gene product may be a small molecule drug target for the treatment of metabolic disease, including obesity and Types 1 and 2 diabetes.  
     [0867] The ubiquitous expression of this gene in this panel also suggests that the protein encoded by this gene plays a role in cell survival and proliferation for a majority of cell types. Furthermore, there are significant levels of expression in the lung cancer cell line SHP-77. Thus, expression of this gene could potentially be used as a diagnostic marker for some forms of lung cancer. Modulation of the gene product may also play role in treating lung cancer.  
     [0868] References:  
     [0869] Matsumoto T, Tamaki T, Kawakami M, Yoshida M, Ando M, Yamada H. Early complications of high-dose methylprednisolone sodium succinate treatment in the follow-up of acute cervical spinal cord injury. Spine Feb. 15, 2001;26(4):426-30  
     [0870] STUDY DESIGN: A prospective, randomized, and double-blind study comparing high-dose methylprednisolone sodium succinate (MPSS) with placebo, in the treatment of patients with acute cervical spinal cord injury. OBJECTIVES: To evaluate the complications of high-dose MPSS in patients with acute cervical spinal cord injury when administered within 8 hours of injury. SUMMARY OF BACKGROUND DATA: High-dose therapy with MPSS has been demonstrated to improve the recovery of motor function in patients with acute cervical spinal cord injury. However, little is known about the follow-up complications. METHODS: Forty-six patients, 42 men and 4 women (mean age, 60.6 years; range, 18-84), were included in the study: 23 in the MPSS group and 23 in the placebo group. They were treated without surgery for spinal cord injury in the cervical spine, and were enrolled in the trial if a diagnosis had been made and treatment had begun within 8 hours. Complications of high-dose therapy with MPSS were compared with placebo treatment throughout the study period and up to 2 months after injury. RESULTS: The MPSS group had 13 patients (56.5%) with complications, whereas the placebo group had 8 (34.8%). The difference between the two groups was not statistically significant (P=0.139). There were eight instances of pulmonary complication with MPSS (34.8%) and one instance (4.34%) with placebo (P=0.009). There were four instances of gastrointestinal complication (17.4%) with MPSS and none with placebo (P=0.036). Pulmonary (complications were more prevalent in patients aged more than 60 years (P=0.029). CONCLUSION: Aged patients with cervical spinal injury may be more likely to have pulmonary side effects (P=0.029) after high-dose therapy with MPSS and thus deserve special care.  
     [0871] Holinka C F.Design and conduct of clinical trials in hormone replacement therapy. Ann N Y Acad Sci September 2001; 943:89-108  
     [0872] Postmenopausal hormone replacement therapy represents an area of outstanding importance in preventive medicine that greatly affects personal well-being as well as public health. The number of women living in the United States who are 50 years or older has been estimated at nearly 50 million. Many of those women are likely to be eligible for postmenopausal hormone replacement, which may consist either of estrogen replacement therapy (ERT) in women without a uterus or, more frequently, estrogen/progestin combination therapy (HRT) in women with a uterus. This chapter first presents an overview of general regulatory requirements pertaining to the design and conduct of clinical studies in support of marketing approval for a drug product. These requirements include, but are not restricted to, studies in HRT. The chapter next discusses the design and conduct of clinical trials in support of marketing approval for the indications: treatment of moderate to severe vasomotor symptoms and vulvovaginal atrophy; prevention of osteoporosis; and protection by adjunctive progestin against estrogen-induced endometrial hyperplasia/cancer in women with a uterus. Finally, data related to the potential cardioprotective action of HRT and its protection against Alzheimer&#39;s disease and colon cancer are discussed.  
     [0873] Burkman R T, Collins J A, Greene R A. Current perspectives on benefits and risks of hormone replacement therapy. Am J Obstet Gynecol August 2001; 185(2 Suppl):S13-23.  
     [0874] Hormone replacement therapy with estrogen alone or with added progestin relieves menopausal symptoms and physical changes associated with depleted endogenous estrogen levels. Estrogen replacement has also demonstrated a clear benefit in the prevention of osteoporosis. Hormone replacement therapy with added progestin maintains spinal bone density, protects against postmenopausal hip fractures, and provides these benefits even when therapy is started after age 60. More recently, additional benefits have emerged. Current estrogen and hormone replacement therapy users have a 34% reduction in the risk of colorectal cancer and a 20% to 60% reduction in the risk of Alzheimer&#39;s disease. Until recently, the body of evidence indicated that hormone replacement therapy with estrogen only reduced cardiovascular disease risk by 40% to 50% in healthy patients; whether the findings of 3 ongoing trials will change this conclusion is pending availability of the final results. The many benefits of estrogen and hormone replacement therapy must be weighed against a slight increase in the risk of breast cancer diagnosis with use for 5 or more years, but which disappears following cessation of therapy. Overall, estrogen and hormone replacement therapy improves the quality of life and increases life expectancy for most menopausal women.  
     [0875] Gaillard P J, van Der Meide P H, de Boer A G, Breimer D D. Glucocorticoid and type 1 interferon interactions at the blood-brain barrier: relevance for drug therapies for multiple sclerosis. Neuroreport Jul. 20, 2000 ;12(10):2189-93.  
     [0876] The pharmacological effect of glucocorticoids and type 1 interferons (IFNs), simultaneously used as therapeuticals for multiple sclerosis (MS), on the (inflamed) blood-brain barrier (BBB) was investigated in vitro. Although both drugs additively decreased BBB permeability, they did not prevent the increase in BBB permeability induced by lipopolysaccharide (LPS), which served as a pro-inflammatory stimulus. The beneficial clinical effect of glucocorticoid and IFN therapy for MS seems there-fore not to be mediated through a direct action at the level of the BBB. Most strikingly, however, pretreatment with type 1 IFNs (alpha and beta) potentiated the effect of glucocorticoids by two orders of magnitude. This lead us to hypothesize that type 1 IFNs may restore the dysfunctional T-helper 1 (Th1)/Th2 balance associated with MS, by a mechanism that involves an increased sensitivity for glucocorticoids.  
     [0877] Panel 2D Summary: Ag2248/Ag2548  
     [0878] The expression of the CG50307-01 gene shows good concordance between two independent runs. The highest level of expression was seen in a breast cancer sample (CTs=27-29). In addition, this gene appears to be overexpressed in ovarian, gastric, breast, uterine, lung and colon cancers relative to the normal adjacent tissues from these patients. Therefore, the expression of this gene could be of use as a diagnostic marker for the presence of these cancers. Furthermore, therapeutic inhibition of the activity of this gene product may be effective in the treatment of these cancers.  
     [0879] Panel 3D Summary: Ag2548  
     [0880] The CG50307-01 gene is expressed at a low to moderate level in most of the cells and tissues used in this panel, with highest expression in the small cell lung cancer cell line DMS-79 (CT=27.79). This ubiquitous expression suggests that the gene product plays a role in cell survival and proliferation for a majority of cell types except cell lines derived from tongue squamous cell carcinoma.  
     [0881] Panel 4D Summary: Ag2248  
     [0882] The CG50307-01 gene encodes a steroid dehydrogenase-like protein and is expressed at moderate levels (CT=28-32) in numerous immune cell types and tissues. Small molecule antagonists that block the function of the steroid dehydrogenase-like protein encoded by this gene may be useful as therapeutics that reduce or eliminate the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis. Please note that data from a second run using the probe and primer set Ag2548 is not included. The amp plot suggests that there were experimental difficulties with this run.  
     [0883] Panel 5 Islet Summary: Ag2248  
     [0884] The expression of this novel steroid dehydrogenase-like gene, CG50307-01, is highest in the liver HepG2 cell line, (CT=32.1). Lower but still significant levels of expression are seen in several placenta samples, uterine smooth muscle, adipose samples, differentiated mesenchymal stem cells, kidney and skeletal muscle from a diabetic patient. Expression in liver cells and placenta suggests that the role of this novel steroid dehydrogenase may be similar to the role of other steroid dehydrogenases which are involved in steroid and bile acid metabolism. Very low expression of this gene is also seen in a human pancreatic islet sample. Therefore, small molecule therapeutics against this gene product may be effective in disorders in which expression of this gene is dysregulated.  
     [0885] Panel 5D Summary: Ag2248  
     [0886] The expression of the CG50307-01 gene is generally similar to that in panel 5I, although the relative abundances in each of the tissues are different. This panel shows highest expression of this steroid dehydrogenase-like gene in placenta from a diabetic patient (CT=32.2), with lower expression in other placenta samples. Relative expression of this gene is also high in the skeletal muscle of a diabetic patient and in liver HepG2 cells. Low but significant levels of expression are also seen in some adipose samples and in differentiated mesenchymal stem cells, in kidney and in uterus. Expression in liver cells and placenta suggests that the role of this novel steroid dehydrogenase may be similar to the role of other steroid dehydrogenases which are involved in steroid and bile acid metabolism. Small molecule therapeutics against this gene product may be effective in disorders in which expression of this gene is dysregulated.  
     [0887] Panel CNS — 1 Summary: Ag2248  
     [0888] This panel confirms expression of the CG50307-01 gene in the brain. Please see Panel 1.3D for discussion of potential utility in the central nervous system.  
     [0889] NOV11 (CG50311-01: Novel Nonmuscle Myosin)  
     [0890] Expression of gene CG50311-01 was assessed using the primer-probe set Ag2546, described in Table LA. Results of the RTQ-PCR runs are shown in Tables LB, LC and LD.  
                   TABLE LA                          Probe Name Ag2546                                                 Start           Primers   Sequences   Length   Position                                             Forward   5′-gttctgtgtggtcatcaatcct-3′   (SEQ ID NO:181)   22   487                   Probe   TET-5′-caagaacctgcccatctactctgaaga-3′-TAMRA    (SEQ ID NO:182)   27   511               Reverse   5′-cttgcccttgtacatttcca-3′   (SEQ ID NO:183)   20   543                  
 
     [0891]               TABLE LB                          Panel 1.3D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2546,       Ag2546,       Tissue Name   Run 165532775   Tissue Name   Run 165532775                                     Liver adenocarcinoma   15.4   Kidney (fetal)   9.0       Pancreas   4.0   Renal ca. 786-0   44.1       Pancreatic ca. CAPAN 2   9.3   Renal ca. A498   38.2       Adrenal gland   3.8   Renal ca. RXF 393   41.5       Thyroid   5.2   Renal ca. ACHN   20.9       Salivary gland   6.7   Renal ca. UO-31   63.7       Pituitary gland   1.4   Renal ca. TK-10   8.7       Brain (fetal)   2.6   Liver   1.5       Brain (whole)   6.8   Liver (fetal)   6.1       Brain (amygdala)   6.4   Liver ca.   15.4               (hepatoblast) HepG2       Brain (cerebellum)   4.5   Lung   19.8       Brain (hippocampus)   4.6   Lung (fetal)   9.5       Brain (substantia nigra)   3.2   Lung ca. (small cell)   10.7               LX-1       Brain (thalamus)   3.7   Lung ca. (small cell)   14.6               NCI-H69       Cerebral Cortex   5.1   Lung ca. (s. cell var.)   19.8               SHP-77       Spinal cord   5.8   Lung ca. (large   11.1               cell)NCI-H460       glio/astro U87-MG   15.9   Lung ca. (non-sm.   3.8               cell) A549       glio/astro U-118-MG   100.0   Lung ca. (non-s. cell)   2.4               NCI-H23       astrocytoma SW1783   54.7   Lung ca. (non-s. cell)   29.7               HOP-62       neuro*; met SK-N-AS   2.7   Lung ca. (non-s. cl)   1.6               NCI-H522       astrocytoma SF-539   27.9   Lung ca. (squam.)   17.8               SW 900       astrocytoma SNB-75   60.3   Lung ca. (squam.)   10.7               NCI-H596       glioma SNB-19   16.3   Mammary gland   12.2       glioma U251   54.0   Breast ca.* (pl. ef)   7.1               MCF-7       glioma SF-295   28.5   Breast ca.* (pl. ef)   64.2               MDA-MB-231       Heart (Fetal)   4.0   Breast ca.* (pl. ef)   4.2               T47D       Heart   9.3   Breast ca. BT-549   52.5       Skeletal muscle (Fetal)   5.3   Breast ca. MDA-N   0.8       Skeletal muscle   6.8   Ovary   14.4       Bone marrow   8.2   Ovarian ca. OVCAR-3   11.1       Thymus   7.7   Ovarian ca. OVCAR-4   19.9       Spleen   12.2   Ovarian ca. OVCAR-5   17.0       Lymph node   28.3   Ovarian ca. OVCAR-8   4.9       Colorectal   13.1   Ovarian ca. IGROV-1   2.8       Stomach   9.3   Ovarian ca. (ascites)   31.2               SK-OV-3       Small intestine   11.5   Uterus   40.6       Colon ca. SW480   8.1   Placenta   9.5       Colon ca.* SW620   7.4   Prostate   3.2       (SW480 met)       Colon ca. HT29   3.6   Prostate ca.* (bone   7.0               met) PC-3       Colon ca. HCT-116   6.9   Testis   2.8       Colon ca. CaCo-2   9.0   Melanoma   22.4               Hs688(A).T       CC Well to Mod Diff   29.3   Melanoma* (met)   27.2       (ODO3866)       Hs688(B).T       Colon ca. HCC-2998   6.8   Melanoma UACC-62   7.1       Gastric ca. (liver met)   15.1   Melanoma M14   51.4       NCI-N87       Bladder   21.9   Melanoma LOX   4.5               IMVI       Trachea   8.5   Melanoma* (met)   6.6               SK-MEL-5       Kidney   5.8   Adipose   14.3                    
     [0892]               TABLE LC                          Panel 2.2                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2546, Run       Ag2546,       Tissue Name   174575196   Tissue Name   Run 174575196                                     Normal Colon   33.4   Kidney Margin   100.0               (OD04348)       Colon cancer (OD06064)   60.7   Kidney malignant   7.9               cancer (OD06204B)       Colon Margin   29.1   Kidney normal adjacent   10.4       (OD06064)       tissue (OD06204E)       Colon cancer (OD06159)   5.7   Kidney Cancer   34.4               (OD04450-01)       Colon Margin   34.6   Kidney Margin   24.8       (OD06159)       (OD04450-03)       Colon cancer (OD06297-   11.7   Kidney Cancer 8120613   1.0       04)       Colon Margin   39.5   Kidney Margin 8120614   19.9       (OD06297-015)       CC Gr.2 ascend colon   6.3   Kidney Cancer 9010320   6.4       (ODO3921)       CC Margin (ODO3921)   7.2   Kidney Margin 9010321   11.1       Colon cancer metastasis   3.0   Kidney Cancer 8120607   35.6       (OD06104)       Lung Margin (OD06104)   16.0   Kidney Margin 8120608   10.9       Colon mets to lung   35.6   Normal Uterus   90.8       (OD04451-01)       Lung Margin (OD04451-   53.6   Uterine Cancer 064011   7.6       02)       Normal Prostate   6.4   Normal Thyroid   1.1       Prostate Cancer   1.8   Thyroid Cancer   6.7       OD04410)       Prostate Margin   4.0   Thyroid Cancer   11.5       (OD04410)       A302152       Normal Ovary   35.8   Thyroid Margin   3.8               A302153       Ovarian cancer   18.6   Normal Breast   61.6       (OD06283-03)       Ovarian Margin   30.4   Breast Cancer   7.6       (OD06283-07)       Ovarian Cancer   11.9   Breast Cancer   40.3       Ovarian cancer   4.4   Breast Cancer   27.9       (OD06145)       (OD04590-01)       Ovarian Margin   22.1   Breast Cancer Mets   31.4       (OD06145)       (OD04590-03)       Ovarian cancer   14.0   Breast Cancer   26.4       (OD06455-03)       Metastasis       Ovarian Margin   15.3   Breast Cancer   33.4       (OD06455-07)       Normal Lung   19.3   Breast Cancer 9100266   15.9       Invasive poor diff. lung   14.1   Breast Margin 9100265   30.4       adeno (ODO4945-01       Lung Margin   33.9   Breast Cancer A209073   9.2       (ODO4945-03)       Lung Malignant Cancer   18.6   Breast Margin   28.5       (OD03126)       A2090734       Lung Margin (OD03126)   6.5   Breast cancer   48.0               (OD06083)       Lung Cancer   21.5   Breast cancer node   35.6       (OD05014A)       metastasis (OD06083)       Lung Margin   44.8   Normal Liver   15.8       (OD05014B)       Lung cancer (OD06081)   8.4   Liver Cancer 1026   16.2       Lung Margin (OD06081)   19.8   Liver Cancer 1025   33.2       Lung Cancer (OD04237-   4.3   Liver Cancer 6004-T   19.6       01)       Lung Margin (OD04237-   58.6   Liver Tissue 6004-N   4.9       02)       Ocular Mel Met to Liver   9.7   Liver Cancer 6005-T   44.8       (OD04310)       Liver Margin   9.0   Liver Tissue 6005-N   64.6       (ODO4310)       Melanoma Metastasis   3.4   Liver Cancer   29.5       Lung Margin (OD04321)   36.6   Normal Bladder   15.1       Normal Kidney   5.3   Bladder Cancer   15.7       Kidney Ca, Nuclear   46.7   Bladder Cancer   21.2       grade 2 (OD04338)       Kidney Margin   4.6   Normal Stomach   54.3       (OD04338)       Kidney Ca Nuclear grade   26.6   Gastric Cancer 9060397   6.4       1/2 (OD04339)       Kidney Margin   15.5   Stomach Margin   22.4       (OD04339)       9060396       Kidney Ca, Clear cell   17.0   Gastric Cancer 9060395   19.3       type (OD04340)       Kidney Margin   20.3   Stomach Margin   35.1       (OD04340)       9060394       Kidney Ca, Nuclear   15.3   Gastric Cancer 064005   11.4       grade 3 (OD04348)                    
     [0893]               TABLE LD                          Panel 4D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag2546, Run       Ag2546, Run       Tissue Name   164321138   Tissue Name   164321138                                     Secondary Th1 act   34.2   HUVEC IL-1beta   26.6       Secondary Th2 act   33.7   HUVEC IFN gamma   45.7       Secondary Tr1 act   34.4   HUVEC TNF alpha + IFN   58.6               gamma       Secondary Th1 rest   15.7   HUVEC TNF alpha + IL4   58.6       Secondary Th2 rest   28.5   HUVEC IL-11   28.5       Secondary Tr1 rest   26.8   Lung Microvascular EC   60.7               none       Primary Th1 act   30.8   Lung Microvascular EC   64.6               TNF alpha + IL-1beta       Primary Th2 act   36.9   Microvascular Dermal EC   66.9               none       Primary Tr1 act   40.9   Microsvasular Dermal EC   61.1               TNF alpha + IL-1beta       Primary Th1 rest   75.8   Bronchial epithelium   66.9               TNF alpha + IL-1beta       Primary Th2 rest   60.3   Small airway epithelium   32.8               none       Primary Tr1 rest   49.7   Small airway epithelium   95.3               TNF alpha + IL-1beta       CD45RA CD4   42.0   Coronery artery SMC rest   61.1       lymphocyte act       CD45RO CD4   39.0   Coronery artery SMC   36.6       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   35.6   Astrocytes rest   66.0       Secondary CD8   41.2   Astrocytes TNF alpha + IL-   46.0       lymphocyte rest       1beta       Secondary CD8   26.1   KU-812 (Basophil) rest   7.6       lymphocyte act       CD4 lymphocyte none   22.2   KU-812 (Basophil)   29.5               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   38.4   CCD1106 (Keratinocytes)   56.6       CD95 CH11       none       LAK cells rest   30.8   CCD1106 (Keratinocytes)   57.0               TNF alpha + IL-1beta       LAK cells IL-2   43.8   Liver cirrhosis   9.8       LAK cells IL-2 + IL-12   37.6   Lupus kidney   6.5       LAK cells IL-2 + IFN   41.2   NCI-H292 none   17.7       gamma       LAK cells IL-2 + IL-18   38.2   NCI-H292 IL-4   26.2       LAK cells   38.4   NCI-H292 IL-9   26.6       PMA/ionomycin       NK Cells IL-2 rest   30.4   NCI-H292 IL-13   19.6       Two Way MLR 3 day   27.2   NCI-H292 IFN gamma   19.2       Two Way MLR 5 day   21.9   HPAEC none   46.0       Two Way MLR 7 day   26.2   HPAEC TNF alpha +   54.0               IL-1beta       PBMC rest   27.5   Lung fibroblast none   46.7       PBMC PWM   71.2   Lung fibroblast TNF alpha +   28.7               IL-1beta       PBMC PHA-L   44.8   Lung fibroblast IL-4   77.4       Ramos (B cell) none   23.7   Lung fibroblast IL-9   68.3       Ramos (B cell)   59.9   Lung fibroblast IL-13   62.0       ionomycin       B lymphocytes PWM   66.9   Lung fibroblast IFN   81.2               gamma       B lymphocytes CD40L   47.6   Dermal fibroblast   77.4       and IL-4       CCD1070 rest       EOL-1 dbcAMP   20.3   Dermal fibroblast   100.0               CCD1070 TNF alpha       EOL-1 dbcAMP   25.9   Dermal fibroblast   54.0       PMA/ionomycin       CCD1070 IL-1beta       Dendritic cells none   23.0   Dermal fibroblast IFN   18.2               gamma       Dendritic cells LPS   25.5   Dermal fibroblast IL-4   27.2       Dendritic cells anti-   26.2   IBD Colitis 2   2.4       CD40       Monocytes rest   31.6   IBD Crohn&#39;s   2.4       Monocytes LPS   17.7   Colon   22.4       Macrophages rest   33.0   Lung   45.4       Macrophages LPS   20.9   Thymus   28.5       HUVEC none   49.0   Kidney   39.5       HUVEC starved   85.9                    
     [0894] Panel 1.3D Summary: Ag2546  
     [0895] The CG50311-01 gene is expressed at moderate levels in all cell lines and tissues in this panel, with highest expression in a glioblastoma/astrocytoma cell line (CT=25.3). There is slightly increased expression in renal and brain cancer cell lines compared to normal tissues suggesting a possible role in these cancers.  
     [0896] This gene is also expressed at moderate levels in all endocrine (metabolic)-related regions examined. Therefore, therapeutic modulation of this gene or its protein product may be of use in the treatment of any endocrine (metabolic)-related disease where neuronal feedback is critical.  
     [0897] This gene encodes a myosin homolog that is expressed at moderate levels in all brain regions examined. Nonmuscle myosin is believed to be involved in the migration of neural growth cones. Therefore, therapeutic modulation of this gene or its protein product may be of use in the treatment of any CNS disease that involves neuronal death/neurodegeneration (Alzheimer&#39;s, Parkinson&#39;s, Huntington&#39;s diseases, stroke, brain or spinal cord trauma) and may also aid in compensatory synaptogenesis.  
     [0898] References:  
     [0899] Kira M, Tanaka J, Sobue K. Caldesmon and low Mr isoform of tropomyosin are localized in neuronal growth cones. J Neurosci Res Feb. 15, 1995;40(3):294-305.  
     [0900] Neuronal growth cones move actively, accompanying changes in intracellular Ca2+ concentration. The movement of growth cones may partly depend on the actomyosin system, considering the presence of actin and myosin II. Yet, Ca(2+)-sensitive regulatory proteins for the actomyosin system have not been identified in growth cones. In the present study, caldesmon, an inhibitory protein on actin-myosin interaction, was detected in the growth cone fraction isolated from embryonic rat brain, using immunoblotting with the antibody to chicken gizzard caldesmon. Morphological evidence of caldesmon in growth cones of cultured rat neurons was obtained using the indirect immunofluorescence method. Since inhibition of caldesmon on actin-myosin interaction can be overcome by calmodulin and Ca2+, caldesmon may be involved in the Ca(2+)-dependent regulation in growth cone motility. Tropomyosin is another member of the actomyosin system whose function may be regulated by caldesmon in smooth and nonmuscle cells. A low Mr isoform of tropomyosin was distributed in the growth cone fraction. Using specific antibodies against tropomyosin isoforms, we further clarified morphologically that the low Mr isoform was localized in growth cones, but not the high Mr isoform. High Mr isoforms of tropomyosin were present in nonneuronal cells. Actin filaments in growth cones may be unstable, since low Mr tropomyosin binds to actin filaments with a lower affinity than high Mr isoforms. The instability of actin filaments may be suitable for the rapid movement and shape changes of growth cones.  
     [0901] Panel 2.2 Summary: Ag2546  
     [0902] The CG50311-01 gene gene is expressed at moderate levels in all the samples on this panel with slightly higher expression in normal lung, breast and stomach tissue compared to the adjacent tumor tissue. Hence, expression of this gene might be used as a marker to identify normal tissue from cancerous tissue in these organs.  
     [0903] Panel 4D Summary: Ag2546  
     [0904] The CG50311-01 gene is expressed at high levels (CTs=24.9-27.4) in a wide range of cell types with significant importance in innate and specific immunity and also other cell types associated with inflammatory diseases. The highest expression of this transcript is found in dermal and lung fibroblasts treated with cytokines, and in small airway epithelium and HUVEC. Therefore, inhibition of the function of the protein encoded by this gene throught the application of a small molecule drug may reduce or eliminate the symptoms associated with T cell, B cell, endothelial and fibroblast activity such as those found in chronic obstructive pulmonary disease, asthma, emphysema, psoriasis, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and lupus erythematosus.  
     [0905] NOV12a (CG50323-01: Pancreatitis-Associated Protein)  
     [0906] Expression of gene CG50323-01 was assessed using the primer-probe set Ag3760, described in Table IA.  
                   TABLE IA                          Probe Name Ag3760                                                 Start           Primers   Sequences   Length   Position                                             Forward   5′-caattgcctccagtatttgaac-3′   (SEQ ID NO:184)   22   506                   Probe   TET-5′-ttgcagacatagggtaacctcacatt-3′-TAMRA    (SEQ ID NO:185)   26   480               Reverse   5′-agcatttctgaggtggaaaga-3′   (SEQ ID NO:186)   21   449                  
 
     [0907] CNS_Neurodegeneration_v1.0 Summary: Ag3760  
     [0908] Expression of the CG50323-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     [0909] General_screening_panel_v1.4 Summary: Ag3760  
     [0910] Expression of the CG50323-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     [0911] Panel 4.1D Summary: Ag3760  
     [0912] Expression of the CG50323-01 gene is low/undetectable in all samples on this panel (CT&gt;35).  
     Example 2  
     [0913] Identification of NOVX Clones  
     [0914] The novel NOVX target sequences identified in the present invention were subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. Table M1 shows the sequences of the PCR primers used for obtaining different clones. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the predicted exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain-amygdala, brain-cerebellum, brain-hippocampus, brain-substantia nigra, brain-thalamus, brain-whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma-Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus.  
                           TABLE M1                       NOVX                   Clone   Forward Primer   Reverse Primer                  NOV1c-   GGATCCAGAATTCTGCAAAATCTTACGACTTTGG   CGGCCGATAGCAGAAGACATCCCACATTTCACTCTTG           NOV1j   (SEQ ID NO:187)   (SEQ ID NO:188)               NOV3b   TGCGCGCTCGTCGTCCTC   GGAGGCCACAGGAGCAGGATCA           (SEQ ID NO:189)   (SEQ ID NO:190)               NOV5b   AGATCTCTGGGCGCAACGGTCATCTGTAACAAGATCC   CTCGAGCTTGCACGTGTACATCTCCGTGCGCTCG           (SEQ ID NO:191)   (SEQ ID NO:192)               NOV6b   GGATCCAGCCCTGGCCAGGCCGTGTGCAACTTCG   CTCGAGTGTGTTCCCCGGGCTGGGGGCAGGCTGC           (SEQ ID NO:193)   (SEQ ID NO:194)               NOV7b   ATGTCTGTGGCCATGGTAGAGTCAGG   ATCATGAACCTCAACTCCTCAGGAACC       and   (SEQ ID NO:195)   (SEQ ID NO:196)       NOV7c               NOV8   CAAGAGCAGGTTTGAGATGTTCTC   CCAAGGTTGACCACCTCCAT           (SEQ ID NO:197)   (SEQ ID NO:198)               NOV10b   ATCTACGGAGTCCCTTTGGCCACATAA   TCCAAATGTCAGAATATCGAGGTTCCC           (SEQ ID NO:199)   (SEQ ID NO:200)               NOV11   CCGCCTGTGTTCCATGGCTT   GTCATTCTGCTGCCGGTTGGTAG           (SEQ ID NO:201)   (SEQ ID NO:202)               NOV12a   CCATGGCCCTGCCAAGTGTATCTT   TTACAATTGCCTCCAGTATTTGAACTTGCA           (SEQ ID NO:203)   (SEQ ID NO:204)               NOV12b   AGCTTGAAGAACCCCAGAGGGAACTGCCCTCTGC   CTCGAGCAATTGCCTCCAGTATTTGAACTTGC       and   (SEQ ID NO:205)   (SEQ ID NO:206)       NOV12c                  
 
     [0915] Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. Table M2 shows a list of these bacterial clones. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation&#39;s database and with public ESTs. Fragments and ESTs were included as components for an assembly when the extent of their identity with another component of the assembly was at least 95% over 50 bp. In addition, sequence traces were evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported herein.  
                           TABLE M2                                   NOVX Clone   Bacterial Clone (Physical clone)                          NOV3a   124906::133267070.698458.L7           NOV8   SC87760822_A.698299.L11           NOV10b   124893::CG50307-01.698453.H17                      
 
     [0916] Real Time Quantitative PCR  
     [0917] Relative expression levels of the mRNA of the invention across a panel of 92 human samples was determined by real-time quantitative PCR analysis. These samples represent multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, cell lines, primary cells or tissue cultured primary cells and cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression for example, growth factors, chemokines, steroids. Table M3 shows the primers/probe used for this reaction. The primers and probe were designed to specifically identify the gene of the invention irresepective of the presence of related human genes like splice forms, homologs and paralogs.  
                               TABLE M3                       NOVX                       Clone   Forward Primer   Reverse Primer   Probe                  NOV8   GCACTTGAAGAGCTGTCATAGC   TACCCTGAGTCTCTTGATTCCA   TET-5′-CTCTATGACTGCCAGCAAATCACACG-3′-TAMRA               (SEQ ID NO:207)   (SEQ ID NO:208)   (SEQ ID NO:209)                  
 
     Example 3  
     [0918] SNP Analysis of NOVX Clones  
     [0919] SeqCallingTM Technology: cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, cell lines, primary cells or tissue cultured primary cells and cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression for example, growth factors, chemokines, steroids. The cDNA thus derived was then sequenced using CuraGen&#39;s proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled with themselves and with public ESTs using bioinformatics programs to generate CuraGen&#39;s human SeqCalling database of SeqCalling assemblies. Each assembly contains one or more overlapping cDNA sequences derived from one or more human samples. Fragments and ESTs were included as components for an assembly when the extent of identity with another component of the assembly was at least 95% over 50 bp. Each assembly can represent a gene and/or its variants such as splice forms and/or single nucleotide polymorphisms (SNPs) and their combinations. Variant sequences are 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, however, in the case that 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 for example, alteration in temporal expression, physiological response regulation, cell type expression regulation, intensity of expression, stability of transcribed message.  
     [0920] Method of novel SNP Identification: SNPs are identified by analyzing sequence assemblies using CuraGen&#39;s proprietary SNPTool algorithm. SNPTool identifies variation in assemblies with the following criteria: SNPs are not analyzed within 10 base pairs on both ends of an alignment; Window size (number of bases in a view) is 10; The allowed number of mismatches in a window is 2; Minimum SNP base quality (PHRED score) is 23; Minimum number of changes to score an SNP is 2/assembly position. SNPTool analyzes the assembly and displays SNP positions, associated individual variant sequences in the assembly, the depth of the assembly at that given position, the putative assembly allele frequency, and the SNP sequence variation. Sequence traces are then selected and brought into view for manual validation. The consensus assembly sequence is imported into CuraTools along with variant sequence changes to identify potential amino acid changes resulting from the SNP sequence variation. Comprehensive SNP data analysis is then exported into the SNPCalling database.  
     [0921] Method of Novel SNP Confirmation:  
     [0922] SNPs are confirmed employing a validated method know as Pyrosequencing (Pyrosequencing, Westborough, Mass.). Detailed protocols for Pyrosequencing can be found in: Alderborn et al. Determination of Single Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. (2000).  Genome Research.  10, Issue 8, August. 1249-1265. In brief, Pyrosequencing is a real time primer extension process of genotyping. This protocol takes double-stranded, biotinylated PCR products from genomic DNA samples and binds them to streptavidin beads. These beads are then denatured producing single stranded bound DNA. SNPs are characterized utilizing a technique based on an indirect bioluminometric assay of pyrophosphate (PPi) that is released from each dNTP upon DNA chain elongation. Following Klenow polymerase-mediated base incorporation, PPi is released and used as a substrate, together with adenosine 5′-phosphosulfate (APS), for ATP sulfurylase, which results in the formation of ATP. Subsequently, the ATP accomplishes the conversion of luciferin to its oxiderivative by the action of luciferase. The ensuing light output becomes proportional to the number of added bases, up to about four bases. To allow processivity of the method dNTP excess is degraded by apyrase, which is also present in the starting reaction mixture, so that only dNTPs are added to the template during the sequencing. The process has been fully automated and adapted to a 96-well format, which allows rapid screening of large SNP panels. The DNA and protein sequences for the novel single nucleotide polymorphic variants are reported. Variants are reported individually but any combination of all or a select subset of variants are also included. In addition, the positions of the variant bases and the variant amino acid residues are underlined.  
     [0923] Results  
     [0924] 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.  
     [0925] NOV1a SNP Data  
     [0926] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the Stablin-like gene of NOV1a are reported in Table N1. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there are 5 variants reported.  
               TABLE N1                          cSNP and Coding Variants for NOV1a                                     Base                       Position of       Variant   cSNP   Wild Type   Variant   Amino Acid Change               13376228   4185   T   C   silent (no change)       13376229   4524   T   C   silent       13376230   4654   G   A   Gly → Ser at aa 1552       13376231   4671   A   G   silent       13376232   4820   T   C   Leu → Pro at aa 1607                  
 
     [0927] NOV2a SNP Data  
     [0928] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the Polydom-like gene of NOV2a are reported in Table N2. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there are 10 variants reported.  
               TABLE N2                          cSNP and Coding Variants for NOV2a                                     Base                       Position of       Variant   cSNP   Wild Type   Variant   Amino Acid Change                                         13374700   717   A   G   Glu → Gly at aa 214       13374701   2303   A   G   Asn → Asp at aa 743       13374256   7348   T   C   silent       13376233   7370   C   T   Pro → ser at aa 2432       13376234   8665   G   A   silent       13376235   8827   C   T   silent       13376236   9018   A   G   His → Arg at aa 2981       13376237   9551   A   G   Thr → Ala at aa 3159       13376238   9790   T   G   silent       13376239   10025   G   T   Gly → End at aa                       3317                  
 
     [0929] NOV3a SNP Data  
     [0930] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the Transmembrane-like gene of NOV3a are reported in Table N3. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there are 4 variants reported.  
               TABLE N3                          cSNP and Coding Variants for NOV3a                                     Base                       Position of       Variant   cSNP   Wild Type   Variant   Amino Acid Change               13376243   145   A   G   Ile → Val at aa 49       13376242   336   G   A   Trp → End at aa 112       13376241   494   G   A   Gly → Asp at aa 165       13376240   495   C   T   silent                  
 
     [0931] NOV4 SNP Data  
     [0932] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the Serine Protease-like gene of NOV4 are reported in Table N4. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there are 3 variants reported.  
               TABLE N4                          cSNP and Coding Variants for NOV4                                     Base Position of                   Variant   cSNP   Wild Type   Variant   Amino Acid Change               13376246   122   G   A   Val → Ile at aa 37       13376245   258   A   G   His → Arg at aa 82       13376244   296   C   T   Arg → Cys at aa 95                  
 
     [0933] NOV5a SNP Data  
     [0934] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the Wnt7a-like gene of NOV5a are reported in Table N5. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there are 2 variants reported.  
               TABLE N5                          cSNP and Coding Variants for NOV5a                                     Base Position   Wild       Amino Acid       Variant   of cSNP   Type   Variant   Change               13376247   315   G   A   silent       13376248   459   T   C   silent                  
 
     [0935] NOV6a SNP Data  
     [0936] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the Apical Endosomal Glycoprotein-like gene of NOV6a are reported in Table N6. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there is 1 variant reported.  
               TABLE N6                          cSNP and Coding Variants for NOV6a                                     Base Position   Wild       Amino Acid       Variant   of cSNP   Type   Variant   Change               13376249   3477   C   T   Pro → Ser at aa 1147                  
 
     [0937] NOV7a SNP Data  
     [0938] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the ADAM13-like gene of NOV7a are reported in Table N7. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there are 2 variants reported.  
               TABLE N7                          cSNP and Coding Variants for NOV7a                                     Base Position   Wild       Amino Acid       Variant   of cSNP   Type   Variant   Change               13374267   2130   G   A   Val → Ile at aa 710       13374266   2153   G   C   silent                  
 
     [0939] NOV8 SNP Data  
     [0940] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the Leucine Rich Containing F-Box Protein-like gene of NOV8 are reported in Table N8. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there are 2 variants reported.  
               TABLE N8                          cSNP and Coding Variants for NOV8a                                     Base Position   Wild       Amino Acid       Variant   of cSNP   Type   Variant   Change               13373958   366   T   C   Ile → Thr at aa 117       13373959   452   C   T   Pro → Ser at aa 146                  
 
     [0941] NOV10a SNP Data  
     [0942] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the Steroid dehydrogenase-like gene of NOV10a are reported in Table N9. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there are 2 variants reported.  
               TABLE N9                          cSNP and Coding Variants for NOV10a                                     Base Position   Wild       Amino Acid       Variant   of cSNP   Type   Variant   Change                                         13375812   465   A   G   Ile → Val at aa95       13375811   1162   C   G   Ser → Cys at aa327                  
 
     [0943] NOV11 SNP Data  
     [0944] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the Myosin Heavy Chain-like gene of NOV11 are reported in Table N10. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there are 4 variants reported.  
               TABLE N10                          cSNP and Coding Variants for NOV11                                     Base Position   Wild       Amino Acid       Variant   of cSNP   Type   Variant   Change               13374341   5008   G   T   silent       13374342   5012   A   G   Ile → Val at aa1625       13376300   6808   C   T   silent       13376299   7323   C   T   silent                  
 
     [0945] NOV12a SNP Data  
     [0946] The DNA and protein sequences for the novel single nucleotide polymorphic variants of the Pacreatitis Associated Protein-like gene of NOV12a are reported in Table N11. Variants are reported individually but any combination of all or a select subset of variants are also included. In summary, there are 8 variants  
               TABLE N11                          cSNP and Coding Variants for NOV12a                                     Base Position   Wild       Amino Acid       Variant   of cSNP   Type   Variant   Change                                         13373957   68   T   C   silent       13373956   127   C   T   Ala → Val at aa 42       13373955   178   A   G   Asp → Gly at aa 59       13373954   182   A   G   silent       13373953   227   G   A   silent       13373952   314   C   T   silent       13373951   341   A   G   silent       13373950   441   A   G   Arg → Gly at aa 147                  
 
     OTHER EMBODIMENTS  
     [0947] 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.