Patent Publication Number: US-2003235821-A1

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

Description:
RELATED APPLICATIONS  
     [0001] This application claims priority to U.S. Ser. No. 60/295,661 filed on Jun. 4, 2001; U.S. Ser. No. 60/295,607 filed on Jun. 4, 2001; U.S. Ser. No. 60/296,404 filed on Jun. 6, 2001; U.S. Ser. No. 60/296,418 filed on Jun. 6, 2001; U.S. Ser. No. 60/296,575 filed on Jun. 7, 2001; U.S. Ser. No. 60/297,414 filed on Jun. 11, 2001; U.S. Ser. No. 60/297,567 filed on Jun. 12, 2001; U.S. Ser. No. 60/298,528 filed on Jun. 15, 2001; U.S. Ser. No. 60/325,685 filed on Sep. 27, 2001; U.S. Ser. No. 60/299,133 filed on Jun. 18, 2001; U.S. Ser. No. 60/299,230 filed on Jun. 19, 2001; U.S. Ser. No. 60/299,949 filed on Jun. 21, 2001; U.S. Ser. No. 60/300,177 filed on Jun. 22, 2001; U.S. Ser. No. 60/318,727 filed on Sep. 12, 2001; U.S. Ser. No. 60/300,883 filed on Jun. 26, 2001; U.S. Ser. No. 601358,814 filed on Feb. 22, 2002; U.S. Ser. No. 60/301,530 filed on Jun. 28, 2001; U.S. Ser. No. 60/301,550 filed on Jun. 28, 2001; and U.S. Ser. No. 60/302,951 filed on July 3, 2001; each of which is incorporated by reference in its entirety. 
    
    
     
       FIELD OF THE INVENTION  
       [0002] The present invention is based in part on nucleic acids encoding proteins that are new members of the following protein families: Leucine Rich Repeat-like  Homo sapiens  proteins, Leucine Rich Repeat proteins, Adenine Nucleotide Translocator 2 (ADP/ATP Translocase 2)-like  Homo sapiens  proteins, Mitochondrial energy transfer protein domain-like  Homo sapiens  proteins, ATRAP-like  Homo sapiens  proteins, Cytosolic phosphoprotein proteins, PAX 3A-like  Homo sapiens  proteins, GRP-1-Associated Scaffold Protein GRASP proteins, Neurabin 1-like  Homo sapiens  proteins, Epidermal fatty acid binding protein-like  Homo sapiens  proteins, Septin 6 (KIAA0128)-like  Homo sapiens  proteins, RIM2-4C-like  Homo sapiens  proteins, Cell Growth Regulator Falkor-like  Homo sapiens -like proteins, Meningioma-Expressed Antigen 6/11 (MEA6) (MEA11)-like  Homo sapiens  proteins, Liprin alpha 4-like  Homo sapiens  proteins, Q9GKW8-like  Homo sapiens  proteins, GTPase Activator Protein-like  Homo sapiens  proteins, PEFLIN-like  Homo sapiens  proteins, Neurotransmitter-gated ion-channel-like  Homo sapiens  proteins, Carboxyl-Terminal PDZ Ligand of Neuronal Nitric Oxide Synthase-like  Homo sapiens  proteins, Amyloid Beta A4 Precursor Protein-Binding Family B Member 2-like  Homo sapiens  proteins, Calreticulin Precursor-like  Homo sapiens  proteins, Protein Kinase C Inhibitor-like  Homo sapiens  proteins, PAX Transcription Activation Domain Interacting Protein PTIP-like  Homo sapiens  proteins, MAP1 Light Chain 3 Related Protein-like  Homo sapiens  proteins, Intacellular signaling protein-like  Homo sapiens  proteins, FISH Protein-like  Homo sapiens  proteins, profilaggrin-like  Homo sapiens  proteins, VP3 domain-containing protein-like  Homo sapiens  proteins, VP3 domain-containing protein-like proteins, PX19-like  Homo sapiens  proteins, Polyubiquitin-like  Homo sapiens  proteins, Pathcalling Protein-like  Homo sapiens  proteins, MYND zinc finger (ZnF) domain-containing protein-like Homo sapiens proteins, Q9N061-like  Homo sapiens  proteins, Stra8-like  Homo sapiens  proteins, Membrane Protein Kinase-like  Homo sapiens  proteins, and Delta 4 3-Oxosteroid 5 Beta Reductase-like  Homo sapiens  proteins.  
       [0003] The invention relates to polynucleotides and the polypeptides encoded by such polynucleotides, as well as vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using the same.  
       BACKGROUND OF THE INVENTION  
       [0004] The invention generally relates to nucleic acids and polypeptides encoded therefrom. More specifically, the invention relates to nucleic acids encoding cytoplasmic, nuclear, membrane bound, and secreted polypeptides, as well as vectors, host cells, antibodies, and recombinant methods for producing these nucleic acids and polypeptides.  
       SUMMARY OF THE INVENTION  
       [0005] The present invention is based in part on nucleic acids encoding proteins that are members of the following protein families: Leucine Rich Repeat-like  Homo sapiens  proteins, Leucine Rich Repeat proteins, Adenine Nucleotide Translocator 2 (ADP/ATP Translocase 2)-like  Homo sapiens  proteins, Mitochondrial energy transfer protein domain-like  Homo sapiens  proteins, ATRAP-like  Homo sapiens  proteins, Cytosolic phosphoprotein proteins, PAX 3A-like  Homo sapiens  proteins, GRP-1-Associated Scaffold Protein GRASP proteins, Neurabin 1-like  Homo sapiens  proteins, Epidermal fatty acid binding protein-like  Homo sapiens  proteins, Septin 6 (KIAA0128)-like  Homo sapiens  proteins, RIM2-4C-like  Homo sapiens  proteins, Cell Growth Regulator Falkor-like  Homo sapiens -like proteins, Meningioma-Expressed Antigen 6/11 (MEA6) (MEA11)-like  Homo sapiens  proteins, Liprin alpha 4-like  Homo sapiens  proteins, Q9GKW8-like  Homo sapiens  proteins, GTPase Activator Protein-like  Homo sapiens  proteins, PEFLIN-like  Homo sapiens  proteins, Neurotransmitter-gated ion-channel-like  Homo sapiens  proteins, Carboxyl-Terminal PDZ Ligand of Neuronal Nitric Oxide Synthase-like  Homo sapiens  proteins, Amyloid Beta A4 Precursor Protein-Binding Family B Member 2-like  Homo sapiens  proteins, Calreticulin Precursor-like  Homo sapiens  proteins, Protein Kinase C Inhibitor-like  Homo sapiens  proteins, PAX Transcription Activation Domain Interacting Protein PTIP-like  Homo sapiens  proteins, MAP1 Light Chain 3 Related Protein-like  Homo sapiens  proteins, Intacellular signaling protein-like  Homo sapiens  proteins, FISH Protein-like  Homo sapiens  proteins, profilaggrin-like  Homo sapiens  proteins, VP3 domain-containing protein-like  Homo sapiens  proteins, VP3 domain-containing protein-like proteins, PX19-like  Homo sapiens  proteins, Polyubiquitin-like  Homo sapiens  proteins, Pathcalling Protein-like  Homo sapiens  proteins, MYND zinc finger (ZnF) domain-containing protein-like  Homo sapiens  proteins, Q9N061-like  Homo sapiens  proteins, Stra8-like  Homo sapiens  proteins, Membrane Protein Kinase-like  Homo sapiens  proteins, and Delta 4 3-Oxosteroid 5 Beta Reductase-like  Homo sapiens  proteins. The novel polynucleotides and polypeptides are referred to herein as NOV1a, NOV2a, NOV3a, NOV4a, NOV5a, NOV6a, NOV7a, NOV8a, NOV9a, NOV10a, NOV11a, NOV12a, NOV13a, NOV14a, NOV15a, NOV16a, NOV17a, NOV18a, NOV19a, NOV20a, NOV21a, NOV22a, NOV23a, NOV24a, NOV24b, NOV24c, NOV25a, NOV26a, NOV27a, NOV28a, NOV29a, NOV30a, NOV31a, NOV31b, NOV32a, NOV33a, NOV34a, NOV35a, NOV36a, NOV36b, NOV37a, NOV37b, NOV38a and NOV39a. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid or polypeptide sequences.  
       [0006] In one aspect, the invention provides an isolated NOVX nucleic acid molecule encoding a NOVX polypeptide that includes a nucleic acid sequence that has identity to the nucleic acids disclosed in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44. In some embodiments, the NOVX nucleic acid molecule will hybridize under stringent conditions to a nucleic acid sequence complementary to a nucleic acid molecule that includes a protein-coding sequence of a NOVX nucleic acid sequence. The invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof. For example, the nucleic acid can encode a polypeptide at least 80% identical to a polypeptide comprising the amino acid sequences of SEQ ID NO:2n, wherein n is an integer between 1 and 44. The nucleic acid can be, for example, a genomic DNA fragment or a CDNA molecule that includes the nucleic acid sequence of any of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.  
       [0007] Also included in the invention is an oligonucleotide, e.g., an oligonucleotide which includes at least 6 contiguous nucleotides of a NOVX nucleic acid (e.g., SEQ ID NO:2n-1, wherein n is an integer between 1 and 44) or a complement of said oligonucleotide. Also included in the invention are substantially purified NOVX polypeptides (SEQ ID NO:2n, wherein n is an integer between 1 and 44). In certain embodiments, the NOVX polypeptides include an amino acid sequence that is substantially identical to the amino acid sequence of a human NOVX polypeptide.  
       [0008] The invention also features antibodies that immunoselectively bind to NOVX polypeptides, or fragments, homologs, analogs or derivatives thereof.  
       [0009] In another aspect, the invention includes pharmaceutical compositions that include therapeutically- or prophylactically-effective amounts of a therapeutic and a pharmaceutically-acceptable carrier. The therapeutic can be, e.g., a NOVX nucleic acid, a NOVX polypeptide, or an antibody specific for a NOVX polypeptide. In a further aspect, the invention includes, in one or more containers, a therapeutically- or prophylactically-effective amount of this pharmaceutical composition.  
       [0010] In a further aspect, the invention includes a method of producing a polypeptide by culturing a cell that includes a NOVX nucleic acid, under conditions allowing for expression of the NOVX polypeptide encoded by the DNA. If desired, the NOVX polypeptide can then be recovered.  
       [0011] In another aspect, the invention includes a method of detecting the presence of a NOVX polypeptide in a sample. In the method, a sample is contacted with a compound that selectively binds to the polypeptide under conditions allowing for formation of a complex between the polypeptide and the compound. The complex is detected, if present, thereby identifying the NOVX polypeptide within the sample.  
       [0012] The invention also includes methods to identify specific cell or tissue types based on their expression of a NOVX.  
       [0013] Also included in the invention is a method of detecting the presence of a NOVX nucleic acid molecule in a sample by contacting the sample with a NOVX nucleic acid probe or primer, and detecting whether the nucleic acid probe or primer bound to a NOVX nucleic acid molecule in the sample.  
       [0014] In a further aspect, the invention provides a method for modulating the activity of a NOVX polypeptide by contacting a cell sample that includes the NOVX polypeptide with a compound that binds to the NOVX polypeptide in an amount sufficient to modulate the activity of said polypeptide. The compound can be, e.g., a small molecule, such as a nucleic acid, peptide, polypeptide, peptidomimetic, carbohydrate, lipid or other organic (carbon containing) or inorganic molecule, as further described herein.  
       [0015] In another embodiment, the invention involves a method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44, the method including providing a cell expressing the polypeptide of the invention and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent.  
       [0016] Also within the scope of the invention is the use of a therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e.g., adrenoleukodystrophy, congenital adrenal hyperplasia, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, autoimmune disease, allergies, immunodeficiencies, Von Hippel-Lindau (VHL) syndrome, Alzheimer&#39;s disease, stroke, tuberous sclerosis, hypercalcemia, Parkinson&#39;s disease, Huntington&#39;s disease, cerebral palsy, epilepsy, Lesch-Nyhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, diabetes, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, renal tubular acidosis, IgA nephropathy, asthma, emphysema, scleroderma, adult respiratory distress syndrome (ARDS), lymphedema, graft versus host disease (GVHD), pancreatitis, obesity, ulcers, anemia, ataxia-telangiectasia, cancer, trauma, viral infections, bacterial infections, parasitic infections and/or other pathologies and disorders of the like. Also within the scope of the invention is the use of a therapeutic in the manufacture of a medicament for treating or preventing conditions including, e.g., transplantation, neuroprotection, fertility, or regeneration (in vitro and in vivo).  
       [0017] The therapeutic can be, e.g., a NOVX nucleic acid, a NOVX polypeptide, or a NOVX-specific antibody, or biologically-active derivatives or fragments thereof.  
       [0018] For example, the compositions of the present invention will have efficacy for treatment of patients suffering from the diseases and disorders disclosed above and/or other pathologies and disorders of the like. The polypeptides can be used as immunogens to produce antibodies specific for the invention, and as vaccines. They can also be used to screen for potential agonist and antagonist compounds. For example, a cDNA encoding NOVX may be useful in gene therapy, and NOVX may be useful when administered to a subject in need thereof.  
       [0019] The invention further includes a method for screening for a modulator of disorders or syndromes including, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like. The method includes contacting a test compound with a NOVX polypeptide and determining if the test compound binds to said NOVX polypeptide. Binding of the test compound to the NOVX polypeptide indicates the test compound is a modulator of activity, or of latency or predisposition to the aforementioned disorders or syndromes.  
       [0020] Also within the scope of the invention is a method for screening for a modulator of activity, or of latency or predisposition to disorders or syndromes including, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like by administering a test compound to a test animal at increased risk for the aforementioned disorders or syndromes. The test animal expresses a recombinant polypeptide encoded by a NOVX nucleic acid. Expression or activity of NOVX polypeptide is then measured in the test animal, as is expression or activity of the protein in a control animal which recombinantly-expresses NOVX polypeptide and is not at increased risk for the disorder or syndrome. Next, the expression of NOVX polypeptide in both the test animal and the control animal is compared. A change in the activity of NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of the disorder or syndrome.  
       [0021] In yet another aspect, the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide, a NOVX nucleic acid, or both, in a subject (e.g., a human subject). The method includes measuring the amount of the NOVX polypeptide in a test sample from the subject and comparing the amount of the polypeptide in the test sample to the amount of the NOVX polypeptide present in a control sample. An alteration in the level of the NOVX polypeptide in the test sample as compared to the control sample indicates the presence of or predisposition to a disease in the subject. Preferably, the predisposition includes, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like. Also, the expression levels of the new polypeptides of the invention can be used in a method to screen for various cancers as well as to determine the stage of cancers.  
       [0022] In a further aspect, the invention includes a method of treating or preventing a pathological condition associated with a disorder in a mammal by administering to the subject a NOVX polypeptide, a NOVX nucleic acid, or a NOVX-specific antibody to a subject (e.g., a human subject), in an amount sufficient to alleviate or prevent the pathological condition. In preferred embodiments, the disorder, includes, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like.  
       [0023] In yet another aspect, the invention can be used in a method to identity the cellular receptors and downstream effectors of the invention by any one of a number of techniques commonly employed in the art. These include but are not limited to the two-hybrid system, affinity purification, co-precipitation with antibodies or other specific-interacting molecules.  
       [0024] NOVX nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel NOVX substances for use in therapeutic or diagnostic methods. These NOVX antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the “Anti-NOVX Antibodies” section below. The disclosed NOVX proteins have multiple hydrophilic regions, each of which can be used as an immunogen. These NOVX proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.  
       [0025] The NOVX nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below. The potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.  
       [0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.  
       [0027] Other features and advantages of the invention will be apparent from the following detailed description and claims.  
       DETAILED DESCRIPTION OF THE INVENTION  
       [0028] The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds. The sequences are collectively referred to herein as “NOVX nucleic acids” or “NOVX polynucleotides” and the corresponding encoded polypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.” Unless indicated otherwise, “NOVX” is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides.  
               TABLE A                          Sequences and Corresponding SEQ ID Numbers                                         SEQ ID                       NO       NOVX   Internal   (nucleic   SEQ ID NO       Assignment   Identification   acid)   (polypeptide)   Homology                                         NOV1a   CG100570-01   1   2   Leucine Rich Repeat-like  Homo sapiens                         proteins       NOV2a   CG100750-01   3   4   Leucine Rich Repeat proteins       NOV3a   CG101201-01   5   6   Adenine Nucleotide Translocator 2                       (ADP/ATP Translocase 2)-like  Homo                           sapiens  proteins       NOV4a   CG101211-01   7   8   Mitochondrial energy transfer protein                       domain-like  Homo sapiens  proteins       NOV5a   CG101274-01   9   10   ATRAP-like  Homo sapiens  proteins       NOV6a   CG101904-01   11   12   Cytosolic phosphoprotein proteins       NOV7a   CG102016-01   13   14   PAX 3A-like  Homo sapiens  proteins       NOV8a   CG102092-01   15   16   GRP-1-Associated Scaffold Protein                       GRASP proteins       NOV9a   CG102595-01   17   18   NEURABIN 1-like  Homo sapiens                         proteins       NOV10a   CG102744-01   19   20   Epidermal fatty acid binding protein-                       like  Homo sapiens  proteins       NOV11a   CG102801-01   21   22   Septin 6 (KIAA0128)-like  Homo                           sapiens  proteins       NOV12a   CG102899-01   23   24   RIM2-4C-like  Homo sapiens  proteins       NOV13a   CG105284-01   25   26   Cell Growth Regulator Falkor-like                         Homo sapiens -                       like proteins       NOV14a   CG105444-01   27   28   Meningioma-Expressed Antigen 6/11                       (MEA6) (MEA11)-like  Homo sapiens                         proteins       NOV15a   CG105482-01   29   30   Meningioma-Expressed Antigen 6/11                       (MEA6) (MEA11)-like  Homo sapiens                         proteins       NOV16a   CG105617-01   31   32   Liprin alpha 4-like  Homo sapiens                         proteins       NOV17a   CG105638-01   33   34   Q9GKW8-like  Homo sapiens  proteins       NOV18a   CG105617-01   35   36   GTPase Activator Protein-like  Homo                           sapiens  proteins       NOV19a   CG105778-01   37   38   PEFLIN-like  Homo sapiens  proteins       NOV20a   CG105796-01   39   40   Neurotransmitter-gated ion-channel-like                         Homo sapiens  proteins       NOV21a   CG106002-01   41   42   Carboxyl-Terminal PDZ Ligand of                       Neuronal Nitric Oxide Synthase-like                         Homo sapiens  proteins       NOV22a   CG106868-01   43   44   Amyloid Beta A4 Precursor Protein-                       Binding Family B Member 2-like  Homo                           sapiens  proteins       NOV23a   CG106988-01   45   46   Calreticulin Precursor-like  Homo                           sapiens  proteins       NOV24a   CG107363-01   47   48   Protein Kinase C Inhibitor-like  Homo                           sapiens  proteins       NOV24b   CG107363-02   49   50   Protein Kinase C Inhibitor-like  Homo                           sapiens  proteins       NOV24c   CG107363-03   51   52   Protein Kinase C Inhibitor-like  Homo                           sapiens  proteins       NOV25a   CG108360-01   53   54   PAX Transcription Activation Domain                       Interacting Protein PTIP-like  Homo                           sapiens  proteins       NOV26a   CG108762-01   55   56   MAP1 Light Chain 3 Related Protein-                       like  Homo sapiens  proteins       NOV27a   CG108829-01   57   58   Intacellular signaling protein-like  Homo                           sapiens  proteins       NOV28a   CG108861-01   59   60   FISH Protein-like  Homo sapiens                         proteins       NOV29a   CG109523-01   61   62   profilaggrin-like  Homo sapiens  proteins       NOV30a   CG109649-01   63   64   Intacellular signaling protein-like  Homo                           sapiens  proteins       NOV31a   CG110063-01   65   66   VP3 domain-containing protein-like                         Homo sapiens  proteins       NOV31b   CG110063-02   67   68   VP3 domain-containing protein-like                       proteins       NOV32a   CG110151-01   69   70   PX19-like  Homo sapiens  proteins       NOV33a   CG110340-01   71   72   Polyubiquitin-like  Homo sapiens                         proteins       NOV34a   CG139264-01   73   74   Pathcalling Protein-like  Homo sapiens                         proteins       NOV35a   CG148240-01   75   76   MYND zinc finger (ZnF) domain-                       containing protein-like  Homo sapiens                         proteins       NOV36a   CG59975-01   77   78   Q9N061-like  Homo sapiens  proteins       NOV36b   CG59975-02   79   80   Q9N061-like  Homo sapiens  proteins       NOV37a   CG89947-01   81   82   Stra8-like  Homo sapiens  proteins       NOV37b   CG89947-02   83   84   Stra8-like  Homo sapiens  proteins       NOV38a   CG93366-02   85   86   Membrane Protein Kinase-like  Homo                           sapiens  proteins       NOV39a   CG97068-02   87   88   Delta 4 3-Oxosteroid 5 Beta Reductase-                       like  Homo sapiens  proteins                  
 
       [0029] Table A indicates homology of NOVX nucleic acids to known protein families. Thus, the nucleic acids and polypeptides, antibodies and related compounds according to the invention corresponding to a NOVX as identified in column 1 of Table A will be useful in therapeutic and diagnostic applications implicated in, for example, pathologies and disorders associated with the known protein families identified in column 5 of Table A.  
       [0030] NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.  
       [0031] Consistent with other known members of the family of proteins, identified in column 5 of Table A, the NOVX polypeptides of the present invention show homology to, and contain domains that are characteristic of, other members of such protein families. Details of the sequence relatedness and domain analysis for each NOVX are presented in Example A.  
       [0032] The NOVX nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVX activity or function. Specifically, the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit diseases associated with the protein families listed in Table A.  
       [0033] The NOVX nucleic acids and polypeptides are also useful for detecting specific cell types. Details of the expression analysis for each NOVX are presented in Example C. Accordingly, the NOVX nucleic acids, polypeptides, antibodies and related compounds according to the invention will have diagnostic and therapeutic applications in the detection of a variety of diseases with differential expression in normal vs. diseased tissues, e.g., a variety of cancers.  
       [0034] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.  
       [0035] NOVX Clones  
       [0036] 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.  
       [0037] The NOVX genes and their corresponding encoded proteins are useful for preventing, treating or ameliorating medical conditions, e.g., by protein or gene therapy. Pathological conditions can be diagnosed by determining the amount of the new protein in a sample or by determining the presence of mutations in the new genes. Specific uses are described for each of the NOVX genes, based on the tissues in which they are most highly expressed. Uses include developing products for the diagnosis or treatment of a variety of diseases and disorders.  
       [0038] The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. These include serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo (vi) biological defense weapon.  
       [0039] In one specific embodiment, the invention includes an isolated polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; and (e) a fragment of any of (a) through (d).  
       [0040] In another specific embodiment, the invention includes an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 44; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44, wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; (e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44, or any variant of said polypeptide wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed; and (f) the complement of any of said nucleic acid molecules.  
       [0041] In yet another specific embodiment, the invention includes an isolated nucleic acid molecule, wherein said nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44; (b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; (c) a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44; and (d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed.  
       [0042] NOVX Nucleic Acids and Polypeptides  
       [0043] 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.  
       [0044] 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.  
       [0045] 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.  
       [0046] 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.  
       [0047] A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or a complement of this aforementioned nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, as a hybridization probe, NOVX molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, et al., (eds.), Molecular Cloning: A Laboratory Manual 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.)  
       [0048] 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.  
       [0049] As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues, which oligonucleotide has a sufficient number of nucleotide bases to be used in a PCR reaction. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise portions of a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.  
       [0050] In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or a portion of this nucleotide sequence (e.g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of an NOVX polypeptide). A nucleic acid molecule a, that is complementary to the nucleotide sequence shown SEQ ID NO:2n-1, wherein n is an integer between 1 and 44 is one that is sufficiently complementary to the nucleotide sequence shown SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, that it can hydrogen bond with little or no mismatches to the nucleotide sequence shown SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, thereby forming a stable duplex.  
       [0051] 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.  
       [0052] 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.  
       [0053] A full-length NOVX clone is identified as containing an ATG translation start codon and an in-frame stop codon. Any disclosed NOVX nucleotide sequence lacking an ATG start codon therefore encodes a truncated C-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length CDNA extend in the 5′ direction of the disclosed sequence. Any disclosed NOVX nucleotide sequence lacking an in-frame stop codon similarly encodes a truncated N-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 3′ direction of the disclosed sequence.  
       [0054] Derivatives and analogs may be fill 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.  
       [0055] A “homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences encode those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for an NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein. Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.  
       [0056] An NOVX polypeptide is encoded by the open reading frame (“ORF”) of an NOVX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG “start” codon and terminates with one of the three “stop” codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bonafide cellular protein, a minimum size requirement is often set, e.g. a stretch of DNA that would encode a protein of 50 amino acids or more.  
       [0057] The nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g. from other tissues, as well as NOVX homologues from other vertebrates. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence SEQ ID NO:2n-1, wherein n is an integer between 1 and 44; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44; or of a naturally occurring mutant of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.  
       [0058] 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.  
       [0059] “A polypeptide having a biologically-active portion of an NOVX polypeptide” refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a “biologically-active portion of NOVX” can be prepared by isolating a portion SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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.  
       [0060] NOVX Nucleic Acid and Polypeptide Variants  
       [0061] The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence shown in SEQ ID NO:2n, wherein n is an integer between 1 and 44.  
       [0062] In addition to the human NOVX nucleotide sequences shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, it will be appreciated by those skilled in the art that DNA sequence polymorphisms that lead to changes in the amino acid sequences of the NOVX polypeptides may exist within a population (e.g., the human population). Such genetic polymorphism in the NOVX genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms “gene” and “recombinant gene” refer to nucleic acid molecules comprising an open reading frame (ORF) encoding 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.  
       [0063] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from the human SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, are intended to be within the scope of the invention. Nucleic acid molecules corresponding to natural allelic variants and homologues of the NOVX cDNAs of the invention can be isolated based on their homology to the human NOVX nucleic acids disclosed herein using the human cDNAs, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions.  
       [0064] Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least 6 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences at least 60% homologous to each other typically remain hybridized to each other.  
       [0065] 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.  
       [0066] 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 defmed 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.  
       [0067] Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), Current Protocols in Molecular Biology, John Wiley &amp; Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6×SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65° C., followed by one or more washes in 0.2×SSC, 0.01% BSA at 50° C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to the sequences SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, corresponds to a naturally-occurring nucleic acid molecule. As used herein, a “naturally-occurring” nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein).  
       [0068] In a second embodiment, a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6×SSC, 5×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 Protocole in Molecular Biology, John Wiley &amp; Sons, NY, and Kriegler, 1990; Gene Transfer and Expression, a Laboratory Manual, Stockton Press, NY.  
       [0069] In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50C. 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.  
       [0070] Conservative Mutations  
       [0071] In addition to naturally-occurring allelic variants of NOVX sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, thereby leading to changes in the amino acid sequences of the encoded NOVX proteins, without altering the functional ability of said NOVX proteins. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence SEQ ID NO:2n, wherein n is an integer between 1 and 44. A “non-essential” amino acid residue is a residue that can be altered from the wild-type sequences of the NOVX proteins without altering their biological activity, whereas an “essential” amino acid residue is required for such biological activity. For example, amino acid residues that are conserved among the NOVX proteins of the invention are predicted to be particularly non-amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.  
       [0072] Another aspect of the invention pertains to nucleic acid molecules encoding NOVX proteins that contain changes in amino acid residues that are not essential for activity. Such NOVX proteins differ in amino acid sequence from SEQ ID NO:2n, wherein n is an integer between 1 and 44, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 45% homologous to the amino acid sequences SEQ ID NO:2n, wherein n is an integer between 1 and 44. Preferably, the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44; more preferably at least about 70% homologous SEQ ID NO:2n, wherein n is an integer between 1 and 44; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44.  
       [0073] An isolated nucleic acid molecule encoding an NOVX protein homologous to the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 44, can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.  
       [0074] Mutations can be introduced into SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted, non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined within the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of an NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity. Following mutagenesis of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.  
       [0075] The relatedness of amino acid families may also be determined based on side chain interactions. Substituted amino acids may be fully conserved “strong” residues or fully conserved “weak” residues. The “strong” group of conserved amino acid residues may be any one of the following groups: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino acid codes are grouped by those amino acids that may be substituted for each other. Likewise, the “weak” group of conserved residues may be any one of the following: CSA, ATV, SAG, STNK, STPA, SGND, SNDEQK, NDEQHK, NEQHRK, HFY, wherein the letters within each group represent the single letter amino acid code.  
       [0076] 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).  
       [0077] 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).  
       [0078] Antisense Nucleic Acids  
       [0079] Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or fragments, analogs or derivatives thereof. An “antisense” nucleic acid comprises a nucleotide sequence that is complementary to a “sense” nucleic acid encoding a protein (e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of an NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 44, or antisense nucleic acids complementary to an NOVX nucleic acid sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, are additionally provided.  
       [0080] 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).  
       [0081] 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).  
       [0082] Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subdloned 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).  
       [0083] The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding an NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.  
       [0084] 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.  
       [0085] Ribozymes and PNA Moieties  
       [0086] 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.  
       [0087] In one embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988.  Nature  334: 585-591) can be used to catalytically cleave NOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. A ribozyme having specificity for an NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of an NOVX cDNA disclosed herein (i.e., SEQ ID NO:2n-1, wherein n is an integer between 1 and 44). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in 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.  
       [0088] 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.  
       [0089] 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.  
       [0090] 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).  
       [0091] 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.  
       [0092] 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. WO 88/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (see, e.g., Krol, et al., 1988.  BioTechniques  6:958-976) or intercalating agents (see, e.g., Zon, 1988.  Pharm. Res.  5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.  
       [0093] NOVX Polypeptides  
       [0094] A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in SEQ ID NO:2n, wherein n is an integer between 1 and 44. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in SEQ ID NO:2n, wherein n is an integer between 1 and 44, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.  
       [0095] 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.  
       [0096] 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.  
       [0097] 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.  
       [0098] 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.  
       [0099] Biologically-active portions of NOVX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the NOVX proteins (e.g., the amino acid sequence shown in SEQ ID NO:2n, wherein n is an integer between 1 and 44) 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.  
       [0100] 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.  
       [0101] In an embodiment, the NOVX protein has an amino acid sequence shown SEQ ID NO:2n, wherein n is an integer between 1 and 44. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 44, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below. Accordingly, in another embodiment, the NOVX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence SEQ ID NO:2n, wherein n is an integer between 1 and 44, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1 and 44.  
       [0102] Determining Homology Between Two or More Sequences  
       [0103] 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”).  
       [0104] The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970.  J Mol Biol  48: 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison: GAP creation penalty of 5.0 and GAP extension penalty of 0.3, the coding region of the analogous nucleic acid sequences referred to above exhibits a degree of identity preferably of at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.  
       [0105] 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.  
       [0106] Chimeric and Fusion Proteins  
       [0107] The invention also provides NOVX chimeric or fusion proteins. As used herein, an NOVX “chimeric protein” or “fusion protein” comprises an NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An “NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to an NOVX protein SEQ ID NO:2n, wherein n is an integer between 1 and 44), whereas a “non-NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a protein that is not substantially homologous to the NOVX protein, e.g., a protein that is different from the NOVX protein and that is derived from the same or a different organism. Within 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.  
       [0108] 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.  
       [0109] 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.  
       [0110] 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.  
       [0111] 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.  
       [0112] NOVX Agonists and Antagonists  
       [0113] 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.  
       [0114] 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.  
       [0115] Polypeptide Libraries  
       [0116] In addition, libraries of fragments of the NOVX protein coding sequences can be used to generate a variegated population of NOVX fragments for screening and subsequent selection of variants of an NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of an NOVX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S 1  nuclease, and ligating the resulting fragment library into an expression vector. By this method, expression libraries can be derived which encodes N-terminal and internal fragments of various sizes of the NOVX proteins.  
       [0117] 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.  
       [0118] Anti-NOVX Antibodies  
       [0119] 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.  
       [0120] 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.  
       [0121] 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.  
       [0122] 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.  
       [0123] 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.  
       [0124] Polyclonal Antibodies  
       [0125] 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).  
       [0126] 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).  
       [0127] Monoclonal Antibodies  
       [0128] 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.  
       [0129] 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.  
       [0130] 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.  
       [0131] 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 Antobody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).  
       [0132] 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.  
       [0133] 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.  
       [0134] 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.  
       [0135] 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.  
       [0136] Humanized Antibodies  
       [0137] 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)).  
       [0138] Human Antibodies  
       [0139] 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).  
       [0140] 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)).  
       [0141] 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.  
       [0142] 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.  
       [0143] 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.  
       [0144] 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.  
       [0145] F ab  Fragments and Single Chain Antibodies  
       [0146] 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.  
       [0147] Bispecific Antibodies  
       [0148] 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.  
       [0149] 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.  
       [0150] 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 Enzymnology,  121:210 (1986).  
       [0151] 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.  
       [0152] 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.  
       [0153] 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.  
       [0154] 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, Gruberetal.,  J. Immunol.  152:5368 (1994).  
       [0155] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al.,  J. Immunol.  147:60 (1991).  
       [0156] 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).  
       [0157] Heteroconjugate Antibodies  
       [0158] 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.  
       [0159] Effector Function Engineering  
       [0160] 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).  
       [0161] Immunoconjugates  
       [0162] 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).  
       [0163] 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.  
       [0164] 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.  
       [0165] 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.  
       [0166] 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.  
       [0167] 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”).  
       [0168] 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 streptavidinibiotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include  125 I,  131 I,  35 S or  3 H.  
       [0169] NOVX Recombinant Expression Vectors and Host Cells  
       [0170] 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.  
       [0171] 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 transcriptionptranslation system or in a host cell when the vector is introduced into the host cell).  
       [0172] 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.).  
       [0173] 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.  
       [0174] 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.  
       [0175] Examples of suitable inducible non-fusion  E. coli  expression vectors include pTrc (Amrann et al., (1 988)  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).  
       [0176] 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.  
       [0177] 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 (Kuijan and Herskowitz, 1982.  Cell  30: 933-943), pJRY88 (Schultz et al., 1987.  Gene  54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).  
       [0178] 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).  
       [0179] 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.  
       [0180] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987.  Genes Dev.  1:268-277), lymphoid-specific promoters (Calame and Eaton, 1988.  Adv. Immunol.  43:235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989.  EMBO J.  8: 729-733) and immunoglobulins (Baneiji, et al., 1983.  Cell  33: 729-740; Queen and Baltimore, 1983.  Cell  33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989.  Proc. Natl. Acad. Sci. USA  86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985.  Science  230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990.  Science  249: 374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989.  Genes Dev.  3: 537-546).  
       [0181] 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.  
       [0182] 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.  
       [0183] 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.  
       [0184] 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.  
       [0185] 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).  
       [0186] 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.  
       [0187] Transgenic NOVX Animals  
       [0188] 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.  
       [0189] A transgenic animal of the invention can be created by introducing NOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g., by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human NOVX cDNA sequences SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, can be introduced as a transgene into the genome of a non-human animal. Alternatively, a non-human homologue of the human NOVX gene, such as a mouse NOVX gene, can be isolated based on hybridization to the human NOVX cDNA (described further supra) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably-linked to the NOVX transgene to direct expression of NOVX protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Pat. Nos. 4,736,866; 4,870,009; and 4,873,191; 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.  
       [0190] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of an NOVX gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g., functionally disrupt, the NOVX gene. The NOVX gene can be a human gene (e.g., the cDNA of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44), but more preferably, is a non-human homologue of a human NOVX gene. For example, a mouse homologue of human NOVX gene of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, can be used to construct a homologous recombination vector suitable for altering an endogenous NOVX gene in the mouse genome. In one embodiment, the vector is designed such that, upon homologous recombination, the endogenous NOVX gene is functionally disrupted (i.e., no longer encodes a functional protein; also referred to as a “knock out” vector).  
       [0191] 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.  
       [0192] 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.  
       [0193] 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.  
       [0194] 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.  
       [0195] Pharmaceutical Compositions  
       [0196] 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.  
       [0197] 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, intradermnal, 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.  
       [0198] 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.  
       [0199] 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.  
       [0200] 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.  
       [0201] 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.  
       [0202] 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.  
       [0203] 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.  
       [0204] 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.  
       [0205] 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.  
       [0206] 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.  
       [0207] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.  
       [0208] Screening and Detection Methods  
       [0209] 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.  
       [0210] The invention farther pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.  
       [0211] Screening Assays  
       [0212] 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.  
       [0213] 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.  Anticaticer Drug Design  12: 145.  
       [0214] 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.  
       [0215] Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt, et al., 1993.  Proc. Natl. Acad. Sci. U.S.A.  90: 6909; Erb, et al., 1994.  Proc. Natl. Acad. Sci. U.S.A.  91: 11422; Zuckermann, et al., 1994.  J. Med. Chem.  37:2678; Cho, et al., 1993.  Science  261: 1303; Carrell, et al., 1994.  Angew. Chem. Int. Ed. Engl.  33:2059; Carell, et al., 1994.  Angew. Chem. Int. Ed. Engl.  33:2061; and Gallop, et al., 1994.  J. Med. Chem.  37: 1233.  
       [0216] Libraries of compounds may be presented in solution (e.g., Houghten, 1992.  Biotechniques  13: 412-421), or onbeads (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. Patent 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.).  
       [0217] 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.  
       [0218] 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.  
       [0219] 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.  
       [0220] 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.  
       [0221] 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.  
       [0222] 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.  
       [0223] The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, Triton® X-114, Thesit®, decanoyl-N-methylglucamide, Tritone® X-100, Isotridecypoly(ethylene glycol ether) n , N-dodecyl--N,N-dimethyl-3-ammonio-1-propane sulfonate, 3-(3-cholamidopropyl)dimethylamminiol-1-propane sulfonate (CHAPS), or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane sulfonate (CHAPSO).  
       [0224] 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.  
       [0225] 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.  
       [0226] 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 MnRNA 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.  
       [0227] 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.  
       [0228] 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.  
       [0229] 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.  
       [0230] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.  
       [0231] Detection Assays  
       [0232] 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.  
       [0233] Chromosome Mapping  
       [0234] Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the NOVX sequences, SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or fragments or derivatives thereof, can be used to map the location of the NOVX genes, respectively, on a chromosome. The mapping of the NOVX sequences to chromosomes is an important first step in correlating these sequences with genes associated with disease.  
       [0235] 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.  
       [0236] 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 flull 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.  
       [0237] 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.  
       [0238] 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).  
       [0239] 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.  
       [0240] 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, Mendellan 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.  
       [0241] 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.  
       [0242] Tissue Typing  
       [0243] 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).  
       [0244] 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.  
       [0245] 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).  
       [0246] Each of the sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers that each yield a noncoding amplified sequence of 100 bases. If predicted coding sequences, such as those in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.  
       [0247] Predictive Medicine  
       [0248] 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, 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.  
       [0249] 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.)  
       [0250] 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.  
       [0251] These and other agents are described in further detail in the following sections.  
       [0252] Diagnostic Assays  
       [0253] An exemplary method for detecting the presence or absence of NOVX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) that encodes NOVX protein such that the presence of NOVX is detected in the biological sample. An agent for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to NOVX mRNA or genomic DNA. The nucleic acid probe can be, for example, a full-length NOVX nucleic acid, such as the nucleic acid of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to NOVX mRNA or genomic DNA. Other suitable probes for use in the diagnostic assays of the invention are described herein.  
       [0254] 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 (ie., 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.  
       [0255] 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.  
       [0256] 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.  
       [0257] 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.  
       [0258] Prognostic Assays  
       [0259] 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.  
       [0260] 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).  
       [0261] 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.  
       [0262] 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.  
       [0263] 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.  
       [0264] 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.  
       [0265] 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.  
       [0266] 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).  
       [0267] 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.  
       [0268] 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.  
       [0269] 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.  
       [0270] 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.  
       [0271] 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.  
       [0272] 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.  
       [0273] 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.  
       [0274] 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.  
       [0275] Pharmacogenomics  
       [0276] 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) various disorders including: 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 as well as diseases disorders associated with homologs of NOVX proteins summarized in Table A. 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.  
       [0277] 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.  
       [0278] 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.  
       [0279] 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.  
       [0280] Monitoring of Effects During Clinical Trials  
       [0281] 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.  
       [0282] 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.  
       [0283] 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, ie., to decrease the effectiveness of the agent.  
       [0284] Methods of Treatment  
       [0285] 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, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, neoplasm; adenocarcinoma, lymphoma, uterus cancer, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn&#39;s disease; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, and other diseases, disorders and conditions of the like. Conditions also include transplantation and fertility.  
       [0286] These methods of treatment will be discussed more fully, below.  
       [0287] Disease and Disorders  
       [0288] 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.  
       [0289] 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.  
       [0290] 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).  
       [0291] Prophylactic Methods  
       [0292] 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.  
       [0293] Therapeutic Methods  
       [0294] 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.  
       [0295] 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).  
       [0296] Determination of the Biological Effect of the Therapeutic  
       [0297] 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.  
       [0298] 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.  
       [0299] Prophylactic and Therapeutic Uses of the Compositions of the Invention  
       [0300] 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.  
       [0301] 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.  
       [0302] 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.  
       [0303] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. 
     
    
    
     EXAMPLES  
     Example A  
     [0304] NOVX Clone Information  
     Example 1  
     [0305] The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1A.  
               TABLE 1A                       NOV1 Sequence Analysis                                                SEQ ID NO:1   3504 bp                     NOV1a,     GCACAGGGATTCCCAGGGCATCTACCACCACGCAGCTGGAGCAGGGCTGAGCCCAGGA                 CG100570-01     GC   ATG GAGATGGACGCCCCCAGGCCCCCCAGTCTTGCTGTCCCTGGAGCAGCATCGAG               DNA Sequence   GCCCGGGAGGAGGGACAGTGTCCAGGATGAAAGCCACGTTTCGTCTGAATGGGGCCTG                   AGCAGGGATGCCAGATCAGATACAGGACACTTGGTCAAATGTGAATTTCAAATAATCC                   ATTTCTTTGCCCCGCTCGGGTCCCGTGGTTCTCAACTCTGGTTAGAACCACCGGAGGA                   GCTTAAACTAGATCCACGTGGGGGCCCTTGCCAGACCAATCAAATCTCTGGGTGGCTG                   CTGGATGGGGGGCACGGCAGGCAGCAGGTTCAGGCCCTCTCTTCACAGCTCCTGGAGG                   TGATCCCCGACTCCATGAGGAAGCAAGAGGTGCGGACGGGCAGGGAGGCCGGCCAGGG                   CCACGGTACGGGCTCCCCAGCCGAGCAGGTGAAAGCCCTCATGGATCTGCTGGCTGGG                   AAGGGCAGTCAAGGCTCCCAGGCCCCGCAGGCCCTGGATAGGACACCGGATGCCCCGC                   TGAGGATACAGAGGCACCGCAAGGCCCTGCTGAGCAAGGTGGGAGGTGGCCCGGAGCT                   GGGCGGACCCTGGCACAGGCTGGCCTCCCTCCTGCTGGTGGAGGGCCTGACGGACCTG                   CAGCTGAGGGAACACGACTTCACACAGGTGGAGGCCACCCGCGGGGGCGGGCACCCCG                   CCAGGACCGTCGCCCTGGACCGGCTCTTCCTGCCTCTCTCCCGGGTGTCTGTCCCACC                   CCGGGTCTCCATCACTATCGGGGTGGCCGGCATGGGCAAGACCACCCTGGTGAGGCAC                   TTCGTCCGCCTCTGGGCCCATGGGCAGGTCGGCAAGGACTTCTCGCTGGTGCTGCCTC                   TGACCTTCCGGGATCTCAACACCCACGAGAAGCTGTGTGCCGACCGACTCATCTGCTC                   GGTCTTCCCGCACGTCGGGGAGCCCAGCCTGGCGGTGGCAGTCCCAGCCAGGGCCCTC                   CTGATCCTGGACGGCTTGGATGAGTGCAGGACGCCTCTGGACTTCTCCAACACCGTGG                   CCTGCACGGACCCAAAGAAGGAGATCCCGGTGGACCACCTGATCACCAACATCATCCG                   TGGCAACCTCTTTCCGGAAGTTTCCATCTGGATCACCTCCCGTCCCAGTGCATCTGGC                   CAGATCCCAGGGGGCCTGGTGGACCGGATGACGGAGATCCGGGGCTTTAACGAGGAGG                   AGATCAAGGTGTGTTTGGAGCAGATGTTCCCCGAGGACCAGGCCCTTCTGGGCTGGAT                   TGCAGGCTCACGGGGATGGCGCTAGGCCACCTGTGGCGCAGCAGGACGGGGCCCCAGG                   ATGCAGAGCTGTGGCCCCCGAGGACCCTGTGCGAGCTCTACTCATGGTACTTTAGGAT                   GGCCCTCAGCGGGGAGGGGCAGGAGAAGGGCAAGGCAAGCCCTCGCATCGAGCAGGTG                   GCCCATGGTGGCCGCAAGATGGTGGGGACATTGGGCCGTCTGGCCTTCCATGGGCTGC                   TCTGCTCCAGGGCGCCCCGTGCAGCTGCTTCCTGCAGAGAGAGGAGACGTTGGCATCG                   TCAGTGGCCTACTGCTTCACCCACCTGTCCCTGCAGGAGTTTGTGGCAGCCGCGTATT                   ACTATGGCGCATCCAGGAGGGCCATCTTCGACCTCTTCACTGAGAGCGGCGTATCCTG                   GCCCAGGCTGGGCTTCCTCACGCATTTCAGGAGCGCAGCCCAGCGGGCCATGCAGGCA                   GAGGACGGGAGGCTGGACGTGTTCCTGCGCTTCCTCTCCGGCCTCTTGTCTCCGAGGG                   TCAATGCCCTCCTGGCCGGCTCCCTGCTGGCCCAAGGCGAGCACCAGGCCTACCGGAC                   CCAGGTGGCTGAGCTCCTGCAGGGCTGCCTGCGCCCCGATGCCGCAGTCTGTGCACGG                   GCCATCAACGTGTTGCACTGCCTGCATGAGCTGCAGCACACCGAGCTGGCCCGCAGCG                   TGGAGGAGGCCATGGAGAGCGGGGCCCTGGCCAGGCTGACTGGTCCCGCGCACCGCGC                   TGCCCTGGCCTACCTCCTGCAGGTGTCCGACGCCTGTGCCCAGGAGGCCAACCTGTCC                   CTGAGCCTCAGCCAGGGCGTCCTTCAGAGCCTGCTGCCCCAGCTGCTCTACTGCCGGA                   AGCTCAGGAGGCTGGACACCAACCAGTTCCAGGACCCCGTGATGGAGCTGCTGGGCAG                   CGTGCTGAGTGGGAAGGACTGTCGCATTCAGAAGATCAGCTTGGCGGAGAACCAGATC                   AGTAACAAAGGGGCCAAAGCTCTGGCCAGATCCCTCTTGGTCAACAGAAGTCTGACCT                   CTCTGAGCCTCCGCGGTAACTCCATTGGACCACAAGGGGCCAAGGCGCTGGCAGACGC                   TTTGAAGATCAACCGCACCCTGACCTCCCTGAGCCTCCAGGGCAACACCGTTAGGGAT                   GATGGTGCCAGGTCCATGGCTGAGGCCTTGGCCTCCAACCGGACCCTCTCCATGCTGC                   AGTTCTCCAGTAATAGTATTGGTGATGGAGGTGCCAAGGCCCTGGCTGAGGCCCTGAA                   GGTGAACCAGGGCCTGGAGAGCCTGAGCCTGCAGAGCAATTCCATCAGTGACGCAGGA                   GTGGCAGCACTGATGGGGGCCCTCTGCACCAACCAGACCCTCCTCAGCCTCAGCCTTC                   GAGAAAACTCCATCAGTCCCGAGGGAGCCCAGGCCATCGCTCATGCCCTCTGCGCCAA                   CAGCACCCTGAAGAACCTGGAGTACGTGGTGGGGGCCTGTGACTCCACAGGCTGTTCA                   TGCCATGACCACACCCACACCGAGCCTGGGCTGACGGGCACCCTCGCCACGAGCCTGA                   CAGCCAACCTCCTCCACGACCAGGGTGCCCGGGCCATCGCAGTGGCAGTGAGAGAAAA                   CCGCACCCTCACCTCCCTTCTGCAGTGGAACTTCATCCAGGCCGGCGCTGCCCAGGCC                   CTGGGACAAGCACTACAGCTCAACAGGAGCCTCACCAGCTTATTACAGGAGAACGCCA                   TCGGGGATGACGGAGCGTGTGCGGTGGCCCGTGCACTGAAGGTCAACACAGCCCTCAC                   TGCTCTCCTCCAGGTGGCCTCAATTGGTGCTTCAGGCGCCCAGGTGCTAGGGGAAGCC                   TTGGCTGTGAACAGAACCTTGGAGATTCTCGAGTTAAGAGGAAATGCCATTGGGGTGG                   CTGGAGCCAAAGCCCTGGCAAATGCTCTGAAGGTAAACTCAAGTCTCCGGAGACTCAA                   G TAA   GTGGCTGGAGGGACCTACCTGCATCCTGGAGCAGCAGAGTTCTCTGCTGGGTCC                       TCCCTGATGGAATAAAATGCTCCT                                       ORF Start: ATG at 61   ORF Stop: TAA at 3424           SEQ ID NO:2   1121 aa MW at 120708.7 kD                     NOV1a,   MEMDAPRPPSLAVPGAASRPGRRDSVQDESHVSSEWGLSRDARSDTGHLVKCEFQIIH               CG100570-01   FFAPLGSRGSQLWLEPPEELKLDPRGGPCQTNQISGWLLDGGHGRQQVQALSSQLLEV               Protein Sequence   IPDSMRKQEVRTGREAGQGHGTGSPAEQVKALMDLLAGKGSQGSQAPQALDRTPDAPL                   RIQRHRKALLSKVGGGPELGGPWHRLASLLLVEGLTDLQLREHDFTQVEATRGGGHPA                   RTVALDRLFLPLSRVSVPPRVSITIGVAGMGKTTLVRHFVRLWAHGQVGKDFSLVLPL                   TFRDLNTHEKLCADRLICSVFPHVGEPSLAVAVPARALLILDGLDECRTPLDFSNTVA                   CTDPKKEIPVDHLITNIIRGNLFPEVSIWITSRPSASGQIPGGLVDRMTEIRGFNEEE                   IKVCLEQMFPEDQALLGWMLSQVQADRALYLMCTVPAFCRLTGMALGHLWRSRTGPQD                   AELWPPRTLCELYSWYFRMALSGEGQEKGKASPRIEQVAHGGRKMVGTLGRLAFHGLL                   KKKYVFYEQDMKAFGVDLALLQGAPCSCFLQREETLASSVAYCFTHLSLQEFVAAAYY                   YGASRRAIFDLFTESGVSWPRLGFLTHFRSAAQRAMQAEDGRLDVFLRFLSGLLSPRV                   NALLAGSLLAQGEHQAYRTQVAELLQGCLRPDAAVCARAINVLHCLHELQHTELARSV                   EEAMESGALARLTGPAHRAALAYLLQVSDACAQEANLSLSLSQGVLQSLLPQLLYCRK                   LRRLDTNQFQDPVMELLGSVLSGKDCRIQKISLAENQISNKGAKALARSLLVNRSLTS                   LSLRGNSIGPQGAKALADALKINRTLTSLSLQGNTVRDDGARSMAEALASNRTLSMLQ                   FSSNSIGDGGAKALAEALKVNQGLESLSLQSNSISDAGVAALMGALCTNQTLLSLSLR                   ENSISPEGAQAIAHALCANSTLKNLEYVVGACDSTGCSCHDHTHTEPGLTGTLATSLT                   ANLLHDQGARAIAVAVRENRTLTSLLQWNFIQAGAAQALGQALQLNRSLTSLLQENAI                   GDDGACAVARALKVNTALTALLQVASIGASGAQVLGEALAVNRTLEILELRGNAIGVA                   GAKALANALKVNSSLRRLK                  
 
     [0306] Further analysis of the NOV1a protein yielded the following properties shown in Table 1B.  
               TABLE 1B                       Protein Sequence Properties NOV1a                                                analysis:   located in nucleus; 0.2221 probability located               in lysosome (lumen); 0.1000 probability               located in mitochondrial matrix space           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0307] A search of the NOV1a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1C.  
               TABLE 1C                          Geneseq Results for NOV1a                                         NOV1a   Identifies/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAG79119   Amino acid sequence of   234 . . . 965   216/780 (27%)     2e−51           inflammatory bowel disease 1    276 . . . 1034   343/780 (43%)             (IBD1) protein -  Homo sapiens ,           1041 aa. [FR2806739-A1, 28-SEP-2001]       AAM01379   Peptide #61 encoded by probe for   388 . . . 476   89/89 (100%)   9e−48           measuring human breast gene    1 . . . 89   89/89 (100%)           expression -  Homo sapiens , 89 aa.           [WO200157270-A2, 09-AUG-2001]       AAM26026   Peptide #63 encoded by probe for   388 . . . 476   89/89 (100%)   9e−48           measuring placental gene    1 . . . 89   89/89 (100%)           expression -  Homo sapiens , 89 aa.           [WO200157272-A2, 09-AUG-2001]       AAM13629   Peptide #63 encoded by probe for   388 . . . 476   89/89 (100%)   9e−48           measuring cervical gene expression -     1 . . . 89   89/89 (100%)             Homo sapiens , 89 aa.           [WO200157278-A2, 09-AUG-2001]       AAM65767   Human bone marrow expressed   388 . . . 476   89/89 (100%)   9e−48           probe encoded protein SEQ ID NO:    1 . . . 89   89/89 (100%)           26073 -  Homo sapiens , 89 aa.           [WO200157276-A2, 09-AUG-2001]                  
 
     [0308] In a BLAST search of public sequence datbases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1D.  
               TABLE 1D                          Public BLASTP Results for NOV1a                                         NOV1a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               BAB84935   FLJ00180 PROTEIN -  Homo     680 . . . 1120   405/472 (85%)   0.0             sapiens  (Human), 499 aa    1 . . . 441   407/472 (85%)           (fragment).       AAM22459   CARD15-LIKE PROTEIN -  Homo     815 . . . 1038   191/253 (75%)   9e−88             sapiens  (Human), 223 aa    1 . . . 223   192/253 (75%)           (fragment).       AAM22460   CARD15-LIKE PROTEIN -  Homo     815 . . . 1011   148/225 (65%)   6e−64             sapiens  (Human), 195 aa    1 . . . 195   155/225 (68%)           (fragment).       CAD10212   SEQUENCE 1 FROM PATENT   234 . . . 965    216/780 (27%)   6e−51           WO0172822 -  Homo sapiens     276 . . . 1034   343/780 (43%)           (Human), 1041 aa.       Q9HC29   Caspase recruitment domain   234 . . . 965    216/780 (27%)   6e−51           protein 15 (Nod2 protein)   275 . . . 1033   343/780 (43%)           (Inflammatory bowel disease           protein 1) -  Homo sapiens             (Human), 1040 aa.                  
 
     [0309] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1E.  
               TABLE 1E                       Domain Analysis of NOV1a                                                Pfam Domain   NOV1a Match Region   Identities/   Expect               Similarities   Value               for the Matched               Region                  
 
     Example 2  
     [0310] The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.  
               TABLE 2A                       NOV2 Sequence Analysis                                                SEQ ID NO:3   2049 bp                     NOV2a,     CTAGACCACAGAAGAAAATACAGAGAGAAC   ATG AAGGCTGAACTACTGGAGACATGGG               CG100750-01   ACAACATCAGTTGGCCTAAAGACCACGTATATATCCGTAATACATCAAAGGACGAACA               DNA Sequence   TGAGGAACTGCAGCGCCTACTGGATCCTAATAGGACTAGAGCCCAGGCCCAGACGATA                   GTCTTGGTGGGGAGGGCAGGGGTTGGGAAGACCACCTTGGCAATGCAGGCTATGCTGC                   ACTGGGCAAATGGAGTTCTCTTTCAGCAAAGGTTCTCCTATGTTTTCTATCTCAGCTG                   CCATAAAATAAGGTACATGAAGGAAACTACCTTTGCTGAATTGATTTCTTTGGATTGG                   CCCGATTTTGATGCCCCCATTGAAGAGTTCATGTCTCAACCAGAGAAGCTCCTGTTTA                   TTATTGATGGCTTTGAGGAAATAATCATATCTGAGTCACGCTCTGAGAGCTTGGATGA                   TGGCTCGCCATGTACAGACTGGTACCAGGAGCTCCCAGTGACCAAAATCCTACACAGC                   TTGTTGAAGAAAGAATTGGTTCCCCTGGCTACCTTACTGATCACGATCAAGACCTGGT                   TTGTGAGAGATCTTAAGGCCTCATTAGTGAATCCATGCTTTGTACAAATTACAGGGTT                   CACAGGGGACGACCTACGGGTATATTTCATGAGACACTTTGATGACTCAAGTGAAGTT                   TCTCCAGTCAATCACTCAGACTACCACCAGTCTGTATGCCTATTTTTTCTCCAACTTG                   TTCTCCACAGCAGAGGTAGATTTGGCAGATGACAGCTGGCCAGGACAATGGAGGGCCC                   TCTGCAGTCTGGCCATAGAAGGGCTGTGGTCTATGAACTTCACGTTTAACAAAGAAGA                   CACTGAGATCGAGGGCCTGGAAGTGCCTTTCATTGATTCTCTCTACGAGTTCAATATT                   CTTCAAAAGATCAATGACTGTGGGGGTTGCACTACTTTCACCCACCTAAGTTTCCAGG                   AGTTTTTTGCAGCCATGTCCTTTGTGCTAGAGGAACCTAGAGAATTCCCTCCCCATTC                   CACAAAGCCACAAGAGATGAAGATGTTACTGCAACACGTCTTGCTTGACAAAGAAGCC                   TACTGGACTCCAGTGGTTCTGTTCTTCTTTGGTCTTTTAAATAAAAACATAGCAAGAG                   AACTGGAAGATACTTTGCATTGTAAAATATCTCCCAGGGTAATGGAGGAATTATTAAA                   CTTTTTCACTGCCTACACGAGTCCCAGGAGGAAGACTTCACAAAGAAGATGTTGGGTC                   GTATCTTTGAAGTTGACCTTAATATTTTGGAGGACGAAGAACTCCAAGCTTCTTCATT                   TTGCCTAAAGCACTGTAAAAGGTTAAATAAGCTAAGGCTTTCTGTTAGCAGTCACATC                   CTTGAAAGGGACTTGGAAATTCTGGAGACAAGCAAGTTTGATTCCAGGATGCACGCAT                   GGAACAGCATTTGCTCTACGTTGGTCACAAATGAGAATCTGCATGAGCTAGACCTGAG                   TAACAGCAAACTTCATGCTTCCTCTGTGAAGGGTCTCTGTCTTGCACTGAAAAATCCA                   AGATGCAAAGTCCAGAAACTGACGCTCAGGTGCAAATCGGTAACTCCTGAGTGGGTTC                   TGCAGGACCTCATTATTGCCCTTCAGGGTAACAGCAAGCTGACCCATCTGAACTTCAG                   CTCTAACAAGCTGGGAATGACTGTCCCCCTGATTCTTAAAGCTTTGAGACACTCAGCT                   TGCAACCTCAAGTATCTGTGG TAA   GTCTTTGGCTCCCTAGATCTGTCAAGGGGGGTTG                       CAAGACCACCAGTAGCTTCCACGATCCACTGGGAGGGCTGACAGCACTCAGCCTTGTA                       GCAAAAGGAGACAGAGAAG                                       ORF Start ATG at 31   ORF Stop: TAA at 1936           SEQ ID NO:4   635 aa MW at 73523.9 kD                     NOV2a,   MKAELLETWDNISWPKDHVYIRNTSKDEHEELQRLLDPNRTRAQAQTIVLVGRAGVGK               CG100750-01   TTLAMQAMLHWANGVLFQQRFSYVFYLSCHKIRYMKETTFAELISLDWPDFDAPIEEF               Protein Sequence   MSQPEKLLFIIDGFEEIIISESRSESLDDGSPCTDWYQELPVTKILHSLLKKELVPLA                   TLLITIKTWFVRDLKASLVNPCFVQITGFTGDDLRVYFMRHFDDSSEVEKILQQLRKN                   ETLFHSCSAPMVCWTVCSCLKQPKVRYYDLQSITQTTTSLYAYFFSNLFSTAEVDLAD                   DSWPGQWRALCSLAIEGLWSMNFTFNKEDTEIEGLEVPFIDSLYEFNILQKINDCGGC                   TTFTHLSFQEFFAAMSFVLEEPREFPPHSTKPQEMKMLLQHVLLDKEAYWTPVVLFFF                   GLLNKNTARELEDTLHCKISPRVMEELLKWGEELGKAESASLQFHILRLFHCLHESQE                   EDFTKKMLGRIFEVDLNILEDEELQASSFCLKHCKRLNKLRLSVSSHTLERDLEILET                   SKFDSRMHAWNSICSTLVTNENLHELDLSNSKLHASSVKGLCLALKNPRCKVQKLTLR                   CKSVTPEWVLQDLIIALQGNSKLTHLNFSSNKLGMTVPLILKALRHSACNLKYLW                  
 
     [0311] Further analysis of the NOV2a protein yielded the following properties shown in Table 2B.  
               TABLE 2B                       Protein Sequence Properties NOV2a                                        PSort   0.5789 probability located in microbody (peroxisome);       analysis:   0.1000 probability located in mitochondrial matrix space;           0.1000 probability located in lysosome (lumen);           0.0000 probability located in endoplasmic reticulum           (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0312] A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2C.  
               TABLE 2C                          Geneseq Results for NOV2a                                         NOV2a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAM50327   Human nucleotide binding site   1 . . . 521   521/521 (100%)   0.0           protein NBS-4 -  Homo sapiens ,   1 . . . 521   521/521 (100%)           521 aa. [WO200183753-A2, 08-NOV-2001]       AAE07514   Human PYRIN-1 protein -  Homo     31 . . . 635    213/642 (33%)    9e−97             sapiens , 1034 aa. [WO200161005-   202 . . . 831    345/642 (53%)            A2, 23-AUG-2001]       AAM50328   Human nucleotide binding site   9 . . . 634   206/628 (32%)    3e−92           protein NBS-5 -  Homo sapiens ,   4 . . . 621   335/628 (52%)            858 aa. [WO200183753-A2, 08-NOV-2001]       ABG28379   Novel human diagnostic protein   1 . . . 634   207/647 (31%)    4e−90           #28370 -  Homo sapiens , 877 aa.   191 . . . 815    333/647 (50%)            [WO200175067-A2, 11-OCT-2001]       AAE07513   Human nucleotide binding site 1   1 . . . 634   207/647 (31%)    4e−90           (NBS-1) protein -  Homo sapiens ,   136 . . . 760    333/647 (50%)            1033 aa. [WO200161005-A2, 23-AUG-2001]                  
 
     [0313] In a BLAST search of public sequence datbases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2D.  
               TABLE 2D                          Public BLASTP Results for NOV2a                                         NOV2a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               CAD19385   SEQUENCE 5 FROM PATENT    1 . . . 521   521/521 (100%)   0.0           WO0183753 -  Homo sapiens      1 . . . 521   521/521 (100%)           (Human), 521 aa.       Q96P20   Cold autoinflammatory syndrome 1    31 . . . 635   213/642 (33%)    2e−96           protein (Cryopyrin) (NACHT-,   202 . . . 831   345/642 (53%)            LRR- and PYD-containing protein           3) (PYRIN-containing APAF1-like           protein 1) (Angiotensin/vasopressin           receptor AII/AVP-like) -  Homo               sapiens  (Human), 1034 aa.       AAL78632   NALP3 LONG ISOFORM -  Homo      31 . . . 635   212/642 (33%)    4e−96             sapiens  (Human), 1036 aa.   204 . . . 833   345/642 (53%)        Q96MN2   CDNA FLJ32126 FIS, CLONE    2 . . . 634   208/635 (32%)    1e−92           PEBLM2000112, WEAKLY    29 . . . 653   338/635 (52%)            SIMILAR TO  Homo sapiens             NUCLEOTIDE-BINDING SITE           PROTEIN 1 MRNA -  Homo sapiens             (Human), 919 aa.       Q96MN2   NACHT-, LRR- and PYD-    2 . . . 634   208/635 (32%)    1e−92           containing protein 4 (PAAD and   104 . . . 728   338/635 (52%)            NACHT-containing protein 2)           (PYRIN-containing APAF1-like           protein 4) (Ribonuclease inhibitor 2) -              Homo sapiens  (Human), 994 aa.                  
 
     [0314] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2E.  
               TABLE 2E                          Domain Analysis of NOV2a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV2a Match Region   for the Matched Region   Value               NB-ARC   32 . . . 65   13/34 (38%)   0.0058               27/34 (79%)                  
 
     Example 3  
     [0315] The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.  
               TABLE 3A                       NOV3 Sequence Analysis                                                SEQ ID NO:5   925 bp                     NOV3a,     CCGCCTGCCTCCTCTTCCTTTCAAC   ATG ACAGATGCCGCTGTGTCCTTGGCCAAGGAC               CG101201-01   TTCCTGGCAGGTGGAGTGACCGCGGCCATCTCCAAGATGGCGGTGGCACCCACGGAGG               DNA Sequence   GGGTCAAGCTGCTGCTGCAGGTGCAGAGTGCCAGCAAGCAGATCACCGCAGATAAGCA                   ATACACGGGCGTTGTAGACTGCATGGTCCGCATTCCCAAGGAGCAGGGAGCAGGAGTC                   CTGTCCCTCTGGCACGGTAACCTGGCCAATGTCATCAGATACTTCCCTACCCACGCTC                   TCAACTTTGCCTTCAAAGATAAAAACAAGCAGATCTTCCCGGGGGGTGTGGACAAGAG                   GATCCAGTTTTGGCACAAGTTTGCAGGGAGTCTGGCATCAGGTGGTGCCCCTGGGGCC                   ACATCCTTATGTTTTGTATACCCTCTTGATTTTGACCGTACCCATCTAGCAGCTGATG                   TGGGTAAAGCTGGAGCTGAAAGGGAATTCCAAGGCCTTGGTGACCGCCTGGTTAAGAT                   CTACAAATCTGATGGGATTAAAGGCCTGTACCAAGGCTCTAACAGCTCTGTGCAGGGT                   ATTATCATCTACCGAGCTGCCTGCTTCGGTGTCTATGACACTGCAAGGAGAATGCTTC                   CAGATTCCAGGAACACTCACGTCATCAGCCGTATGATCGCGCAGTCCGTCACTGCCGT                   TGCTGGGTTGACTTCCTATCCATTTGACGCTGTTCGCCACGGAATGATGATGCAGTCA                   GGGCAGGGTGCAGCTGACATCATGTACACAGGCAGGCTTCACTGCTGGAGGAAGATTG                   CTCCTGATGAAGGAGGCAGAGCTTTTTTCAAGGGTGCATGGTCCAATGTTCTCAGAGG                   CATGGGTGGTGCGTTTGTGCTTGTCTTGTATGATGAAATCAGAAAGTACACA TAA                                       ORF Start: ATG at 26   ORF Stop: TAA at 923           SEQ ID NO:6   299 aa MW at 32484.2 kD                     NOV3a,   MTDAAVSLAKDFLAGGVTAAISKMAVAPTEGVKLLLQVQSASKQITADKQYTGVVDCM               CG101201-01   VRIPKEQGAGVLSLWHGNLANVIRYFPTHALNFAFKDKNKQIFPGGVDKRIQFWHKFA               Protein Sequence   GSLASGGAPGATSLCFVYPLDFDRTHLAADVGKAGAEREFQGLGDRLVKIYKSDGIKG                   LYQGSNRSVQGIIIYRAACFGVYDTARRMLPDSRNTHVISRMIAQSVTAVAGLTSYPF                   DAVRHGMMMQSGQGAADIMYTGRLHCWRKIAPDEGGRAFFKGAWSNVLRGMGGAFVLV                   LYDEIRKYT                  
 
     [0316] Further analysis of the NOV3a protein yielded the following properties shown in Table 3B.  
               TABLE 3B                       Protein Sequence Properties NOV3a                                        PSort   0.6400 probability located in microbody (peroxisome);       analysis:   0.3600 probability located in mitochondrial matrix space;           0.3088 probability located in lysosome (lumen);           0.3000 probability located in mitochondrial           intermembrane space       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0317] A search of the NOV3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3C.  
               TABLE 3C                          Geneseq Results for NOV3a                                         NOV3a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAU10379   Human adenine nucleotide   1 . . . 299   249/300 (83%)   e−137           translocator 2 (ANT2) -  Homo     1 . . . 298   262/300 (87%)             sapiens , 298 aa. [WO200185944-           A2, 15-NOV-2001]       AAU01199   Human adenine nucleotide   1 . . . 299   249/300 (83%)   e−137           translocator-2 (ANT-2) protein -   1 . . . 298   262/300 (87%)             Homo sapiens , 298 aa.           [WO200132876-A2, 10-MAY-2001]       AAY71032   Human adenine nucleotide   1 . . . 299   249/300 (83%)   e−137           translocator ANT2 -  Homo sapiens ,   1 . . . 298   262/300 (87%)           298 aa. [WO200026370-A2, 11-MAY-2000]       AAU10380   Human adenine nucleotide   1 . . . 297   235/298 (78%)   e−130           translocator 3 (ANT3) -  Homo     1 . . . 296   255/298 (84%)             sapiens , 298 aa. [WO200185944-           A2, 15-NOV-2001]       AAU01200   Human adenine nucleotide   1 . . . 297   235/298 (78%)   e−130           translocator-3 (ANT-3) protein -   1 . . . 296   255/298 (84%)             Homo sapiens , 298 aa.           [WO200132876-A2, 10-MAY-2001]                  
 
     [0318] In a BLAST search of public sequence datbases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3D.  
               TABLE 3D                          Public BLASTP Results for NOV3a                                         NOV3a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q09073   ADP, ATP carrier protein, fibroblast   1 . . . 299   251/300 (83%)   e−138           isoform (ADP/ATP translocase 2)   1 . . . 298   263/300 (87%)           (Adenine nucleotide translocator 2)           (ANT 2) -  Rattus norvegicus  (Rat),           298 aa.       P05141   ADP, ATP carrier protein, fibroblast   1 . . . 299   251/300 (83%)   e−138           isoform (ADP/ATP translocase 2)   1 . . . 298   263/300 (87%)           (Adenine nucleotide translocator 2)           (ANT 2) -  Homo sapiens  (Human),           298 aa.       P51881   ADP, ATP carrier protein, fibroblast   1 . . . 299   250/300 (83%)   e−137           isoform (ADP/ATP translocase 2)   1 . . . 298   262/300 (87%)           (Adenine nucleotide translocator 2)           (ANT 2) -  Mus musculus  (Mouse),           298 aa.       A29132   ADP, ATP carrier protein T2 -   1 . . . 299   249/300 (83%)   e−137           human, 298 aa.   1 . . . 298   262/300 (87%)       BAB84673   ADENINE NUCLEOTIDE   1 . . . 299   248/300 (82%)   e−137           TRANSLOCATOR 2 -  Bos taurus     1 . . . 298   262/300 (86%)           (Bovine), 298 aa.                  
 
     [0319] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3E.  
               TABLE 3E                          Domain Analysis of NOV3a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV3a Match Region   for the Matched Region   Value               mito_carr    7 . . . 107   32/125 (26%)   2.4e−23               87/125 (70%)       mito_carr   114 . . . 210   35/125 (28%)   8.7e−17               82/125 (66%)       mito_carr   211 . . . 299   24/125 (19%)   0.00024               64/125 (51%)                  
 
     Example 4  
     [0320] The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A.  
               TABLE 4A                       NOV4 Sequence Analysis                                                SEQ ID NO:7   6075 bp                     NOV4a,     ACGGCAATGGTTTCTTCCAACCACCACCACCTGACAACCCTGC   ATG GCGGCTGCCCCC               CG101211-01   TCCGCGCTGCTTCTGCTGCCGCCCTTTCCAGTCCTCTCTACCTATCGGCTCCAGAGCC               DNA Sequence   GCAGTCGTCCTTCCGCCCCAGAGACCGATGATAGTCGAGTTGGGGGCATTATGAGAGG                   AGAGAAAAACTACTACTTCCGTGGAGCTGCGGGGGACCACGGTTCCTGCCCCACTACA                   ACTTCGCCTCTGGCCTCGGCCCTCTTGATGCCCTCGGAGGCAGTCTCAAGCAGCTGGT                   CTGAGTCTGGAGGCGGTTTGTCAGGGGGAGATGAAGAGGACACTCGGCTCCTTCAACT                   CCTCCGCACTGCCCGGGATCCTTCTGAGGCCTTCCAGGCTTTGCAAGCTGCTTTGCCG                   CGGCGGGGCGGTCGACTTGGCTTCCCCCGACGCAAGGAAGCTTTGTATCGGGCACTGG                   GCCGAGTGCTTGTGGAAGGAGGTAGTGATGAGAAGCGGCTCTGCTTGCAACTTCTCTC                   GGACGTTCTCCGGGGTCAGGGGGAGGCAGGCCAGCTTGAAGAGGCCTTTAGCTTAGCA                   CTTTTGCCTCAACTAGTTGTCTCGTTACGGGAAGAGAATCCAGCCCTGCGGAAAGATG                   CGCTGCAGATCCTTCATATATGTCTGAAACGTAGTCCTGGAGAGGTGCTGAGAACGCT                   TATACAACAAGGACTGGAAAGTACCGATGCCCGACTTAGAGCTTCCACAGCACTACTG                   CTTCCCATCTTGCTTACTACTGAGCACTTGTTGCTTGGTCTGGATCTCACCGAGGTGA                   TAATATCCCTAGCCCGAAAGCTTGGTGATCAGGAGACAGAAGAAGAATCTGAGACAGC                   ATTTCTCGTCTGCCCTCTGCCCTGAGGAGACACTACAATCGCCGCCTGGAGTCCCAGT                   TTGGAAGTCAGGTTCCTTATTATTTGGAACTTGAAGCCTCTGGATTTCCTGAAGATCC                   CCTTCCCTGTGCAGTGACTCTTTCCAACAGCAATCTTAAATTTGGGATTATTCCTCAG                   GAGCTGCATTCACGATTATTGGATCAGGAAGACTATAAGAACCGGACCCAGGCCGTCG                   TGTTGGCTTCATTAGTTTGCTATATAATTTGTTAGACGATTCTAACTTCAAAGTGGTG                   CATGGCACACTTGAAGTCCTCCATTTACTGGTTATTCGCCTTGGAGAGCAGGTACAGC                   AGTTCTTGGGACCAGTTATAGCAGCTTCTGTCAAAGTGCTGGCGGACAACAAGTTGGT                   GATCAAACAAGAATACATGAAAATCTTCCTCAAGCTAATGAAGGAAGTAGGACCTCAG                   CAGGTGCTTTGTTTACTCCTGAAACATCTCAAACATAAGCATTCCAGAGTGAGAGAGG                   AGGTGGTGAACATTTGCATCTGCTCCCTGCTGACCTATCCTAGTGAGGATTTTGACTT                   GCCCAAACTGTCCTTTGATCTTGCCCCAGCTCTTGTAGATAGCAAACGCAGGGTACGC                   CAAGCAGCTTTAGAAGCTTTTGCCGTATTGGCATCATCAATGGGCTCAGGTAAAACCA                   GCATCCTTTTTAAAGCTGTGGATACAGTTGAACTGCAAGATAATGGAGATGGAGTGAT                   GAATGCTGTGCAGGCCAGATTGGCTAGGAAAACCTTACCAAGGCTCACAGAGCAGGGA                   TTTGTGGAATATGCAGTACTGATGCCATCTTCTGCCGGGGGTAGGTCAAACCATTTGG                   CACATGGAGCAGATACGGACTGGCTTTTGGCTGGTAACAGAACTCAGAGTGCACACTG                   TCACTGTGGTGACCACGTGAGGGATAGCATGCACATTTATGGATCTTACAGCCCAACT                   ATCTGTACCCGAAGGGTATTAAGTGCAGGAAAAGGAAAAAATAAATTACCATGGGAAA                   ATGAGCAACCTGGAATCATGGGAGAAAACCAGACCTCCACTTCCAAGGATATAGAGCA                   GTCAATGATGATTTATGTTTTAGCAGAAAAAGAGTATCAAGAAACTTATTTCAGAATA                   GTCGGGATTTTAACCCAGATTGTCTTCCTTTATGTGCTGCTGGTACTACTGGGACTCA                   ACTGGCAGTGTGGGTTCTGACTTACAATTCCTAGGGACAACTAGCAGTCATCAAGAAA                   AAGTGTATGCTAGCCTCAATTTTGGCAGTAAGACACAGCAAACATTTGGTAGTCAAAC                   TATCCTGTCTCATCACCTCGAACTAGTCCAAAGCATACATCTCCTCTTATTATATCTC                   CAAAGAAGTCTCAAGATAATTCTGTTAATTTCTCAAATTCCTGCCCTCTTAAAAGCTT                   CGAAGGACTATCAAAGCCAAGTCCACAGAAGAAGCTTGTCAGCCAAAAATCGTCTGAT                   CCTACGGGTAGAAATCATGGAGAAAATTCTCAAGAAAAACCTCCAGTTCAGCTTACAC                   CTGCCTTGGTGAGATCGCCATCTTCCCGACGAGGTCTAAATGGGACAAAGCCTGTTCC                   TCCCATACCAAGGGGAATAAGCCTTTTGCCTGATAAAGCTGATTTAAGCACAGTGGGA                   CACAAAAAGAAAGAGCCTGATGATATTTGGAAGTGTGAAAAAGATAGTCTTCCAATTG                   ATCTTTCAGAATTAAATTTCAAGGATAAAGATTTGGATCAAGAAGAGATGCATAGCTC                   TCTTAGGTCCCTTCGTAATAGTGCAGCTAAGAAAAGAGCAAAACTGAGTGGCAGTACT                   TTAGATCTTGAAAGCCCTGATTCTGCAATGAAGCTCGACTTGACGATGGACTCCCCGT                   CTCTGTCTTCCTCACCAAACATCAATTCTTACAGTGAAAGTGGAGTTTACAGCCAAGA                   ATCATTGACTTCTTCTCTGTCTACAACTCCCCAGGGGAAGAGAATAATGTCAGACATA                   TTTCCAACATTTGGGTCAAAACCTTGTCCAACAAGACTTTCTTCTGCAAAGAAAAAAA                   TTTCTCATATTGCTGAACAAAGCCCCAGTGCAGGGTCATCATCAAATCCACAGCAAAT                   TTCCAGTTTTGACTTCACAACCACAAAGGCTTTATCAGAAGACTCAGTAGTAGTTGTT                   GGAAAAGGCGTATTTGGAAGTTTAAGTTCAGCACCAGCAACCTGCAGCCAATCAGTGA                   TATCTTCTGTGGAAAATGGGGATACATTTTCAATTAAACAAAGTATTGAACCACCATC                   AGGGATTTATGGAAGATCAGTCCAGCAAAATATTTCATCATATCTTGATGTTGAGAAT                   GAAAAAGATGCTAAAGTTTCTATTTCTAAATCTACTTATAACAAGATGAGACAAAAGA                   GAAAAGAAGAGAAAGAACTGTTTCACAATAAAGATTGTGAAAAGAAGGAAAAAAATTC                   CTGGGAACGAATGAGACATACAGGAACTGAGAAAATGGCATCTGAAAGTGAAACACCT                   ACTGGAGCTATTTCACAGTATAAAGAAAGGATGCCTTCTGTCACTCATAGTCCAGAAA                   TAATGGATCTGTCAGAACTACGACCATTCTCTAAACCAGAAATAGCACTGACAGAAGC                   CCTGAGGCTTTTGGCTGATGAGGATTGGGAGAAGAAAATTGAGGGACTGAATTTTATT                   AGATGCTTAGCTGCTTTTCATTCTGAGATACTGAACACAAAGTTGCATGAAACAAATT                   TTGCAGTTGTTCAAGAGGTGAAAAATTTACGTTCTGGAGTTTCTCGTGCTGCTGTGGT                   CTGTTTAAGTGATCTTTTCACTTATTTGAAAAAGAGCATGGATCAAGAGCTAGATACC                   ACAGTAAAAGTTTTGTTGCACAAGGCTGGTGAATCAAATACATTTATAAGAGAAGATG                   TTGACAAAGCATTGAGAGCTATGGTTAATAATGTAACTCCTGCACGTGCAGTTGTTTC                   TCTTATCAATGGTGGACAAAGGTATTATGGTCGAAAGATGCTGTTCTTCATGATGTGT                   CATCCTAACTTTGAAAAAATGCTTGAAAAGTATGTCCCATCTAAAGATTTGCCATATA                   TTAAGGACTCTGTTAGAAACTTACAGCAAAAGGGTTTGGGGGAGATACCATTAGATAC                   TCCTTCAGCAAAAGGAAGACGATCTCATACTGGCAGTGTTGGAAATACAAGATCATCA                   TCTGTTTCTAGAGATGCTTTCAATTCAGCTGAAAGAGCTGTAACTGAAGTTCGTGAAG                   TCACCAGAAAATCAGTCCCTCGTAATTCCTTAGAAAGTGCTGAGTACCTTAAACTCAT                   AACTGGCTTATTAAATGCAAAAGACTTTCGTGATCGTATTAATGGGATTAAGCAGCTT                   TTATCAGATACAGAAAATAATCAAGACCTTGTTGTTGGAAACATTGTGAAGATTTTTG                   ATGCTTTTAAATCTCGACTTCATGATTCTAATAGTAAAGTAAATCTGGTGGCTCTGGA                   AACAATGCACAAAATGATTCCTCTACTTAGAGACCACTTATCTCCTATAATCAACATG                   CTAATTCCAGCAATAGTGGATAACAATCTGAATTCCAAGAATCCAGGCATCTATGCGG                   CTGCTACAAATGTTGTTCAGGCACTGAGTCAGCATGTAGACAATTACTTACTTCTACA                   GCCATTTTGCACAAAAGCTCAGTTTTTAAATGGAAAAGCAAAACAGGACATGACGGAA                   AAGCTTGCTGATATTGTTACGGAACTTTATCAAAGGAAGCCGCATGCCACAGAGCAGA                   AAGTGTTGGTTGTTTTATGGCATCTCTTAGGAAATATGACAAATAGTGGCTCTCTGCC                   TGGAGCTGGAGGAAATATACGAACAGCCACAGCTAAATTATCAAAAGCACTCTTTGCA                   CAGATGGGTCAGAATCTGTTAAATCAGGCTGCATCTCAACCACCACATATCAAAAAGA                   GTTTGGAGGAATTACTCGATATGACAATTTTAAATGAATTAT GA   ATCTTCGATAAAAT                     ACTGTATGATGAACAAAAGTGTTTACATGATGACAAATGGAACTTTCTAAAAGTTATG                     TTATCAGTGCCTGCACTTCACATCCAGCAAATTAAGTCAATGGCTATTTTTATTTGCA                       GCCTATGAGTACACATCTGTCCTATATCAACCTTACCACTTATATTCATCACATAAAA                       ACCTAAAATATTCATGAATAATTCATGAAATCTGAGTCACATGGGATGAATTCAATTT                       TAATATTTTTGAGAAAAGTCCTGCTCATTTGCACTATTCTATAGAAACTACAATTTGT                       TGCCCTATATGTAAAATTAGAATTGTAATTAAAAATACACATTTTATTATGTAATCAT                       GTTCTGGTATGTCTCATTTCTCAGCCTTATTTTATAACGTGGAAGTCATTGAACTATG                       TTATCAGAAACTAAGTTTGTATATTATTTGTGAAAAACATGTATTTCTGAATCAGTCC                       GCTAATATGATTGTGCAGTATTAGCTTGCTTTTGCTGCTGTGTTAATGTCATATATTT                       GCTTACCTTTTGGGTTCAATTATCTACATAATTGTGAAATTTAACAAGTTATAATAAA                       GCATGACAACCAAAGTTTTAGAAAACATTAAACATTTTAAATGCACGTTTAAAAAACG                       TGTTGAATGTAACCCCCCTATTTTTGTGTGCAAACACTAAATTTTATTGCTTTATGTT                       TTGACCTTTATAAAGGTGTTATTCTGCTGCCCAGTTTTGTAATTCTCAAAAATAGTGC                       CAGGTCTTCTATAGCTTTTTTCAGAATTCATGGGCTTACAAGTACTGTATGCATCTTT                       AAAAAGAAAAGGAATGTTATAAAATAAAAGGATTTATTTCTTT                                       ORF Start: ATG at 44   ORF Stop: TGA at 5204           SEQ ID NO:8   1720 aa MW at 189383.1 kD                     NOV4a,   MAAAPSALLLLPPFPVLSTYRLQSRSRPSAPETDDSRVGGIMRGEKNYYFRGAAGDHG               CG101211-01   SCPTTTSPLASALLMPSEAVSSSWSESGGGLSGGDEEDTRLLQLLRTARDPSEAFQAL               Protein Sequence   QAALPRRGGRLGFPRRKEALYRALGRVLVEGGSDEKRLCLQLLSDVLRGQGEAGQLEE                   AFSLALLPQLVVSLREENPALRKDALQILHICLKRSPGEVLRTLIQQGLESTDARLRA                   STALLLPILLTTEDLLLGLDLTEVIISLARKLGDQETEEESETAFSALQQIGERLGQD                   RFQSYISRLPSALRRHYNRRLESQFGSQVPYYLELEASGFPEDPLPCAVTLSNSNLKF                   GIIPQELHSRLLDQEDYKNRTQAVEELKQVLGKFNPSSTPHSSLVGFISLLYNLLDDS                   NFKVVHGTLEVLHLLVIRLGEQVQQFLGPVIAASVKVLADNKLVIKQEYMKIFLKLMK                   EVGPQQVLCLLLKHLKHKHSRVREEVVNICICSLLTYPSEDFDLPKLSFDLAPALVDS                   KRRVRQAALEAFAVLASSMGSGKTSILFKAVDTVELQDNGDGVMNAVQARLARKTLPR                   LTEQGFVEYAVLMPSSAGGRSNHLAHGADTDWLLAGNRTQSAHCHCGDHVRDSMHIYG                   SYSPTICTRRVLSAGKGKNKLPWENEQPGIMGENQTSTSKDIEQFSTYDFIPSAKLKL                   SQGMPVNDDLCFSRKRVSRNLFQNSRDFNPDCLPLCAAGTTGTHQTNLSGKCAQLGFS                   QICGKTGSVGSDLQFLGTTSSHQEKVYASLNFGSKTQQTFGSQTECTSSNGQNPSPGA                   YILPSYPVSSPRTSPKHTSPLIISPKKSQDNSVNFSNSWPLKSFEGLSKPSPQKKLVS                   QKSSDPTGRNHGENSQEKPPVQLTPALVRSPSSRRGLNGTKPVPPIPRGISLLPDKAD                   LSTVGHKKKEPDDIWKCEKDSLPIDLSELNFKDKDLDQEEMHSSLRSLRNSAAKKRAK                   LSGSTLDLESPDSAMKLDLTMDSPSLSSSPNINSYSESGVYSQESLTSSLSTTPQGKR                   IMSDIFPTFGSKPCPTRLSSAKKKISHIAEQSPSAGSSSNPQQISSFDFTTTKALSED                   SVVVVGKGVFGSLSSAPATCSQSVISSVENGDTFSIKQSIEPPSGIYGRSVQQNISSY                   LDVENEKDAKVSISKSTYNKMRQKRKEEKELFHNKDCEKKEKNSWERMRHTGTEKMAS                   ESETPTGAISQYKERMPSVTHSPEIMDLSELRPFSKPEIALTEALRLLADEDWEKKIE                   GLNFIRCLAAFHSEILNTKLHETNFAVVQEVKNLRSGVSRAAVVCLSDLFTYLKKSMD                   QELDTTVKVLLHKAGESNTFIREDVDKALRAMVNNVTPARAVVSLINGGQRYYGRKML                   FFMMCHPNFEKMLEKYVPSKDLPYIKDSVRNLQQKGLGEIPLDTPSAKGRRSHTGSVG                   NTRSSSVSRDAFNSAERAVTEVREVTRKSVPRNSLESAEYLKLITGLLNAKDFRDRIN                   GIKQLLSDTENNQDLVVGNIVKIFDAFKSRLHDSNSKVNLVALETMHKMIPLLRDHLS                   PIINMLIPAIVDNNLNSKNPGIYAAATNVVQALSQHVDNYLLLQPFCTKAQFLNGKAK                   QDMTEKLADIVTELYQRKPHATEQKVLVVLWHLLGNMTNSGSLPGAGGNIRTATAKLS                   KALFAQMGQNLLNQAASQPPHIKKSLEELLDMTILNEL                  
 
     [0321] Further analysis of the NOV4a protein yielded the following properties shown in Table 4B.  
               TABLE 4B                       Protein Sequence Properties NOV4a                                        PSort   0.5231 probability located in outside;       analysis:   0.1900 probability located in lysosome (lumen);           0.1000 probability located in endoplasmic reticulum           (membrane);           0.1000 probability located in endoplasmic reticulum (lumen)       SignalP   Cleavage site between residues 19 and 20       analysis:                  
 
     [0322] A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4C.  
               TABLE 4C                          Geneseq Results for NOV4a                                         NOV4a                       Residues/   Identities/       Geneseq   Protein/Organism/Length   Match   Similarities for the   Expect       Identifier   [Patent #, Date]   Residues   Matched Region   Value               AAM78886   Human protein SEQ ID NO   1 . . . 1720   1716/1720 (99%)    0.0           1548 -  Homo sapiens , 1720 aa.   1 . . . 1720   1719/1720 (99%)            [WO200157190-A2, 09-AUG-2001]       AAM79870   Human protein SEQ ID NO   1 . . . 1720   1710/1721 (99%)    0.0           3516 -  Homo sapiens , 1721 aa.   1 . . . 1721   1714/1721 (99%)            [WO200157190-A2, 09-AUG-2001]       ABG10016   Novel human diagnostic protein #   42 . . . 1714    1673/1673 (100%)   0.0           10007 -  Homo sapiens , 1677   1 . . . 1673   1673/1673 (100%)           aa. [WO200175067-A2, 11-OCT-2001]       ABG10016   Novel human diagnostic protein #   42 . . . 1714    1673/1673 (100%)   0.0           10007 -  Homo sapiens , 1677   1 . . . 1673   1673/1673 (100%)           aa. [WO200175067-A2, 11-OCT-2001]       ABG10018   Novel human diagnostic protein #   1385 . . . 1690      278/307 (90%)   e−151           10009 -  Homo sapiens , 1047   27 . . . 322     281/307 (90%)           aa. [WO200175067-A2, 11-OCT-2001]                  
 
     [0323] In a BLAST search of public sequence datbases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4D.  
               TABLE 4D                          Public BLASTP Results for NOV4a                                         NOV4a               Protein       Residues/   Identities/       Accession       Match   Similarities for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value               BAA24853   KIAA0423 PROTEIN -  Homo       1 . . . 1720   1720/1720 (100%)   0.0             sapiens  (Human), 1723 aa     4 . . . 1723   1720/1720 (100%)           (fragment).       Q9Y4F4   KIAA0423 PROTEIN -  Homo      25 . . . 1720   1696/1696 (100%)   0.0             sapiens  (Human), 1696 aa     1 . . . 1696   1696/1696 (100%)           (fragment).       Q17423   B0024.8 PROTEIN -   131 . . . 615    137/504 (27%)   2e−35             Caenorhabditis elegans , 1185 aa.    59 . . . 535    233/504 (46%)       T18643   hypothetical protein B0024.8 -   131 . . . 625    141/518 (27%)   1e−34             Caenorhabditis elegans , 537    59 . . . 522    230/518 (44%)           aa.       Q9VPK5   CG4648 PROTEIN -   1232 . . . 1386    51/160 (31%)   1e−16             Drosophila melanogaster     701 . . . 860    86/160 (52%)           (Fruit fly), 953 aa.                  
 
     [0324] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4E.  
               TABLE 4E                       Domain Analysis of NOV4a                                                Pfam   NOV4a Match Region   Identities/   Expect Value       Domain       Similarities               for the Matched               Region                  
 
     Example 5  
     [0325] The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5A.  
               TABLE 5A                       NOV5 Sequence Analysis                                                SEQ ID NO:9   653 bp                     NOV5a,     GCCCTCGGCCTGA   GT CGGGATGGAGCTGCCTGCTGTGAACCTGAAGGTGATTCTCCTA               CG101274-01   GGTCACTGGCTGCTGACAACCTGGGGCTGCATTGTATCCTCAGGCTCCTATGCCTGGG               DNA Sequence   CCAACTTCACCATCCTGGCCTTGGGCGTGTGGGCTGTGGCTCAGCGGGACTCCATCGA                   CGCCATAAGCATGTTTCTGGGTGGCTTGCTCGCCACCATCTTCCTGGACATCGTGCAC                   ATCAGCATCTTCTACCCGCGGGTCAGCCTCACGGACACGGGCCGCTTTGGCGTGGGCA                   TGGCCATCCTCAGCTTGCTGCTCAAGCCGCTCTCCTGCTGCTTCGTCTACCACATGTA                   CCGGGAGCGCGGGGGTGAGCTCCTGGTCCACACTGGTNTCCTTGGGTCTTCTCAGGAC                   CGTAGTGCCTACCAGACGATTGACTCAGCAGAGGCGCCCGCAGATCCCTTGCAGTCCC                   GAAGGCAGGAGTCAGATCCCGAGGGTCTGAGCCAGCCGCTGCCGGCCTCCCGGCCTCT                   CTCTGGAGGGTTAGGTTCT ACC   CTTTGACCAAGATTTCCCTGGTTGAATAGGGACCGG                       TCCCCTTCCTTTATTTCCTTTTTTTTTAGCATCAAAAAAGATCCGCACAGAGGCTTTC                       TTNNNNNNNNNNNNN                                       ORF Start: at 14   ORF Stop: at 542           SEQ ID NO:10   176 aa MW at 18893.6 kD                     NOV5a,   MELPAVNLKVILLGHWLLTTWGCIVSSGSYAWANFTILALGVWAVAQRDSIDAISMFL               CG101274-01   GGLLATIFLDIVHISIFYPRVSLTDTGRFGVGMAILSLLLKPLSCCFVYHMYRERGGE               Protein Sequence   LLVHTGXLGSSQDRSAYQTIDSAEAPADPLQSRRQESDPEGLSQPLPASRPLSGGLGS                   TL                  
 
     [0326] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B.  
               TABLE 5B                       Protein Sequence Properties NOV5a                                        PSort   0.6000 probability located in plasma membrane;       analysis:   0.4000 probability located in Golgi body;           0.3000 probability located in endoplasmic reticulum           (membrane); 0.1000 probability located in mitochondrial           inner membrane       SignalP   Cleavage site between residues 23 and 24       analysis:                  
 
     [0327] A search of the NOV5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 5C.  
               TABLE 5C                          Geneseq Results for NOV5a                                         NOV5a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAB73100   Human angiotensin II-I receptor -   1 . . . 160   148/160 (92%)   1e−79             Homo sapiens , 159 aa.   1 . . . 154   149/160 (92%)           [WO200119864-A1, 22-MAR-2001]       AAM25822   Human protein sequence SEQ ID   1 . . . 160   148/160 (92%)   1e−79           NO: 1337 -  Homo sapiens , 161 aa.   3 . . . 156   149/160 (92%)           [WO200153455-A2, 26-JUL-2001]       AAM79565   Human protein SEQ ID NO: 3211 -   1 . . . 160   148/160 (92%)   1e−79             Homo sapiens , 161 aa.   3 . . . 156   149/160 (92%)           [WO200157190-A2, 09-AUG-2001]       AAM78581   Human protein SEQ ID NO: 1243 -   1 . . . 160   148/160 (92%)   1e−79             Homo sapiens , 159 aa.   1 . . . 154   149/160 (92%)           [WO200157190-A2, 09-AUG-2001]       ABB12006   Human glioblastoma-derived   1 . . . 160   148/160 (92%)   1e−79           protein homologue, SEQ ID   3 . . . 156   149/160 (92%)           NO: 2376 -  Homo sapiens , 161 aa.           [WO200157188-A2, 09-AUG-2001]                  
 
     [0328] In a BLAST search of public sequence datbases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5D.  
               TABLE 5D                          Public BLASTP Results for NOV5a                                         NOV5a   Identities/           Protein       Residues/   Similarities for the       Accession       Match   Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96PL4   AGTRAP PROTEIN -  Homo     1 . . . 160   148/160 (92%)   3e−79             sapiens  (Human), 159 aa.   1 . . . 154   149/160 (92%)       Q9NRW9   ATRAP -  Homo sapiens  (Human),   1 . . . 160   148/160 (92%)   3e−79           159 aa.   1 . . . 154   149/160 (92%)       Q96AC0   SIMILAR TO ANGIOTENSIN II,   1 . . . 160   141/160 (88%)   7e−73           TYPE I RECEPTOR-   1 . . . 147   142/160 (88%)           ASSOCIATED PROTEIN -  Homo               sapiens  (Human), 152 aa.       Q9WVK0   AT1 RECEPTOR-ASSOCIATED   1 . . . 157   117/160 (73%)   2e−60           PROTEIN -  Mus musculus     1 . . . 160   130/160 (81%)           (Mouse), 161 aa.       Q9D940   ANGIOTENSIN II, TYPE I   1 . . . 148   115/149 (77%)   3e−60           RECEPTOR-ASSOCIATED   1 . . . 149   125/149 (83%)           PROTEIN -  Mus musculus             (Mouse), 161 aa.                  
 
     [0329] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5E.  
               TABLE 5E                       Domain Analysis of NOV5a                                                Pfam   NOV5a Match Region   Identities/   Expect       Domain       Similarities   Value               for the Matched Region                  
 
     Example 6  
     [0330] The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A.  
               TABLE 6A                       NOV6 Sequence Analysis                                                SEQ ID NO:11   1980 bp                     NOV6a,     GGTCCCTGGACGCGGAACAGAGATCCCCTGATTCAGCCACCCCCAGACTGAGCCCCGT                 CG101904-01     AGAGTGCGTTCTTACCTTCCTGCCCCGACGAAGGTCCCAGAGACGCTGCGGACAACAC                 DNA Sequence     CAGC   ATG TCGAGCGAGCAGAGCGCGCCGGGGGCCTCACCCAGGGCCCCGCGTCCGGGG                   ACCCAGAAGTCTTCTGGCGCGGTGACCAAAAAGGGAGAGCGCGCGGCCAAAGAGAAGC                   CAGCGACCGTTCTGCCTCCCGTGGGGGAGGAGGAGCCCAAAAGCCCTGAGGAGTACCA                   GTGCTCCGGGGTCCTCGAGACCGACTTCGCCGAGCTCTGCACGCGGTGGGGCTACACG                   GACTTCCCCAAAGTTGTCAACCGGCCCCGCCCCCACCCGCCCTTCGTCCCCTCCGCCT                   CTTTGTCGGAAAAGGCCACCTTAGACGATCCGCGGCTGTCGGGGTCCTGCAGCCTCAA                   TAGCCTGGAGAGCAAATACGTGTTCTTCCGGCCCACCATCCAGGTGGAGCTGGAGCAG                   GAGGACAGCAAGTCAGTGAAGGAAATCTACATCCGCGGTTGGAAGGTTGAGGAACGGA                   TTCTGGGTGTCTTCTCTAAATGTCTGCCCCCGCTTACCCAGCTACAGGCCATCAACTT                   GTGGAAGGTGGGGCTGACCGATAAGACCCTGACCACCTTCATCGAGCTCCTGCCTCTC                   TGTTCATCCACGCTCAGAGGTTCTCGCTCTCCTTCCTGGCTGCCTGGGGCTCTGGCCC                   TGTACTGGGGGCTGATCTCCCCTGCCCTCAGGAAGGTGTCTCTGGAGGGGAACCCACT                   GCCGGAGCAGTCCTATCACAAGCTCATGGCCTTGGACAGCACGATTGCGCACTTGTCT                   CTGCGGAACAATAACATCGACGACCGCGGGGCGCAACTCCTGGGCCAGGCGCTGTCCA                   CGCTGCACAGCTGCAACCGGACCCTCGTCTCGCTCAACCTGGGTTTCAACCACATCGG                   TGACGAGGGCGCAGGCTACATCGCGGACGGCCTCCGGCTGAACCGTTCCCTGCTCTGG                   CTGTCCCTGGCCCACAACCGCATCCAGGACAAGGGCGCCCTGAAGCTGGCTGAGGTCC                   TGCGCGCCTTCGAGCTGACACACACCGAAGTGGTGGAGCGCCGACGCCTCCTGCTGGA                   AAAAGGGACACAGGAGCGCTCGCGATCGCCCTCCTCCTCTCGACACGGGGACTCCAAA                   ACGGACCGTGAGAAGAGTCAGATGGTAGGGATCAGCAATAGTGCATTGGTGGACAAGA                   CAGACAAGACGCAGACAATGAAAACCCCTAAGGGCCTGGGCAAGAAAAAGGAGAAATC                   ATGGGAATTGGCCAAGAAAGAGGAGAAGTTGGGGTCTGGGCAGTCACCCACACAAGGA                   ACCCCTAAGAAGGAAGATGCCACAAAGGCAGGCAAGGGGAAGGTAACCATCCCTGAAC                   AGAAGCCAAGCAGGGCAAAAGGGATCAAGATCGGGAGCAGAGAGAAGCGCAGCATCCT                   CCTGGAGTCCGAGCTGGTTGTTGAGGCTACTGAGGTGGTCAACCCTCTCCTGGAGCCT                   GTGGAGCACCGAGATGGGAAAGTTTTCATGCCTGGGAACAAGGTCCTTTTGCACCTCA                   ACCTCATCCGGAACCGCATCACAGAGGTGGGGCTGGAGGGCTTCCTCGCCACGGTGCA                   GTATCAGATGCAGTTCTCCAAGGCCAAGAGTGCATCCAAGGGTCCAGTGGGGCTGCTG                   TGGCTGTCCCTGGCTAAAAATTGCTTCGCCCCACAATGTCCTGCGTACGCCATAATCC                   AGGAGCTGATGTTGCCAAGGGATCCCATCAAGGCCAAACTCAGGGAGGATGAGGCCAT                   GGCATTCTTCCCC TAG   CCCCCTCCCACCTGCTTGCCTCTAAGACTCGGGGCTACAGAA                       GCACCTCCTGTCCCTGTGTGGGGTGACCTCCCTGGGGGAGATCTCAGACCAATAACAA                       AGTCTGTT                                       ORF Start: ATG at 121   ORF Stop: TAG at 1870           SEQ ID NO:12   583 aa MW at 64375.2 kD                     NOV6a,   MSSEQSAPGASPRAPRPGTQKSSGAVTKKGERAAKEKPATVLPPVGEEEPKSPEEYQC               CG101904-01   SGVLETDFAELCTRWGYTDFPKVVNRPRPHPPFVPSASLSEKATLDDPRLSGSCSLNS               Protein Sequence   LESKYVFFRPTIQVELEQEDSKSVKEIYIRGWKVEERILGVFSKCLPPLTQLQAINLW                   KVGLTDKTLTTFIELLPLCSSTLRGSRSPSWLPGALALYWGLISPALRKVSLEGNPLP                   EQSYHKLMALDSTIAHLSLRNNNIDDRGAQLLGQALSTLHSCNRTLVSLNLGFNHIGD                   EGAGYIADGLRLNRSLLWLSLAHNRIQDKGALKLAEVLRAFELTHTEVVERRRLLLEK                   GTQERSRSPSSSRHGDSKTDREKSQMVGISNSALVDKTDKTQTMKTPKGLGKKKEKSW                   ELAKKEEKLGSGQSPTQGTPKKEDATKAGKGKVTIPEQKPSRAKGIKIGSREKRSILL                   ESELVVEATEVVNPLLEPVEHRDGKVFMPGNKVLLHLNLIRNRITEVGLEGFLATVQY                   QMQFSKAKSASKGPVGLLWLSLAKNCFAPQCPAYAIIQELMLPRDPIKAKLREDEAMA                   FFP                  
 
     [0331] Further analysis of the NOV6a protein yielded the following properties shown in Table 6B.  
               TABLE 6B                       Protein Sequence Properties NOV6a                                        PSort   0.4500 probability located in cytoplasm;       analysis:   0.3000 probability located in microbody (peroxisome);           0.1000 probability located in mitochondrial matrix space;           0.1000 probability located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0332] A search of the NOV6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6C.  
               TABLE 6C                          Geneseq Results for NOV6a                                         NOV6a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAG79119   Amino acid sequence of   221 . . . 328   43/111 (38%)   1e−07           inflammatory bowel disease 1   846 . . . 952   57/111 (50%)           (IBD1) protein -  Homo sapiens ,           1041 aa. [FR2806739-A1, 28-SEP-2001]       ABG14217   Novel human diagnostic protein #   220 . . . 329   38/115 (33%)   2e−06           14208 -  Homo sapiens , 356 aa.   165 . . . 275   58/115 (50%)           [WO200175067-A2, 11-OCT-2001]       ABG14217   Novel human diagnostic protein #   220 . . . 329   38/115 (33%)   2e−06           14208 -  Homo sapiens , 356 aa.   165 . . . 275   58/115 (50%)           [WO200175067-A2, 11-OCT-2001]       AAR35073   Mouse t-complex associated testes   208 . . . 330   45/150 (30%)   2e−06           expressed protein 1 -  Mus musculus ,   320 . . . 469   67/150 (44%)           497 aa. [WO9306859-A, 15-APR-1993]       AAU80865   Human CARD3X protein #2 -  Homo     224 . . . 328   41/105 (39%)   3e−06             sapiens , 1009 aa. [WO200190156-   770 . . . 870   56/105 (53%)           A2, 29-NOV-2001]                  
 
     [0333] In a BLAST search of public sequence datbases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6D.  
               TABLE 6D                          Public BLASTP Results for NOV6a                                         NOV6a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9D3W5   4933430H15RIK PROTEIN -    1 . . . 580   452/581 (77%)   0.0             Mus musculus  (Mouse), 558 aa.    1 . . . 557   492/581 (83%)       Q96M24   CDNA FLJ32884 FIS, CLONE   240 . . . 549   307/311 (98%)    e−170           TESTI2004229 -  Homo sapiens      1 . . . 311   308/311 (98%)           (Human), 354 aa.       BAB84935   FLJ00180 PROTEIN -  Homo     216 . . . 329    45/117 (38%)   2e−10             sapiens  (Human), 499 aa   125 . . . 237    66/117 (55%)           (fragment).       Q93ZV8   HYPOTHETICAL 64.7 KDA   208 . . . 329    48/127 (37%)   9e−10           PROTEIN -  Arabidopsis thaliana     326 . . . 448    72/127 (55%)           (Mouse-ear cress), 605 aa.       AAM22460   CARD15-LIKE PROTEIN-   226 . . . 329    43/107 (40%)   5e−09             Homo sapiens  (Human), 195 aa    1 . . . 103    60/107 (55%)           (fragment).                  
 
     [0334] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6E.  
               TABLE 6E                       Domain Analysis of NOV6a                                                Pfam   NOV6a Match Region   Identities/   Expect       Domain       Similarities   Value               for the Matched Region                  
 
     Example 7  
     [0335] The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A.  
               TABLE 7A                       NOV7 Sequence Analysis                                                SEQ ID NO:13   687 bp                     NOV7a,     TTGACTGTATCGCCGGAATTC   ATG ACCACGCTGGCCGGCGCTGTGCCCAGGATGATGC               CG102016-01   GGGCGGGCCCGGGGGAAAATAACCCGCGTAGCGGGTTCCCGCTGGAAGTGTCCACTCC   TAA               DNA Sequence   CCTCGGCCAGGGCCGCGTCAACCAGCTCGGCGGCGTTTTTATCAACGGCAGGCCGCTG                   CCCAACCACATCCGCCACAAGATCGTGGAGATGGCCCACCACGGCATCCGGCCCTGCG                   TCATCTCGCGCCAGCTGCGCGTGTCCCACGGCTGCGTCTCCAAGATCCTGTCCAGGTA                   CCAGGAGACTGGCTCCATACGTCCTGGTGCCATCGGCGGCAGCAAGCCCAAGGTGACA                   ACGCCTGACGTGGAGAAGAAAATTGAGGAATACAAAAGAGAGAACCCGGGCATGTTCA                   GCTGGGAAATCCGAGACAAATTACTCAAGGACGCGGTCTGTGATCGAAACACCGTGCC                   GTCAGTGAGTTCCATCAGCCGCATCCTGAGAAGTAAATTCGGGAAAGGTGAAGAGGAG                   GAGGCCGACTTGGAGAGGAAGGAGGCAGAGGAAAGCGAGAAGAAGGCCAAACACAGCA                   TCGACGGCATCCTGAGCGAGCGAGGTAAGCGGTGGCGCCTTGGGCGGCGCACTTGCTG                   GGTGACTTGGAGGCATCGGCTAGC TGA   CTGCAGCCAAGCTAATTCCGG                                       ORF Start: ATG at 22   ORF Stop: TGA at 664           SEQ ID NO:14   214 aa MW at 23933.3 kD                     NOV7a,   MTTLAGAVPRMMRAGPGENNPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHK               CG102016-01   IVEMAHHGIRPCVISRQLRVSHGCVSKILCRYQETGSIRPGAIGGSKPKVTTPDVEKK               Protein Sequence   IEEYKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERK                   EAEESEKKAKHSIDGILSERGKRWRLGRRTCWVTWRASAS                  
 
     [0336] Further analysis of the NOV7a protein yielded the following properties shown in Table 7B.  
               TABLE 7B                       Protein Sequence Properties NOV7a                                        PSort   0.7600 probability located in nucleus;       analysis:   0.1000 probability located in mitochondrial matrix space;           0.1000 probability located in lysosome (lumen);           0.0000 probability located in endoplasmic reticulum           (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0337] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7C.  
               TABLE 7C                          Geneseq Results for NOV7a                                         NOV7a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABG20865   Novel human diagnostic protein #    1 . . . 194   191/195 (97%)    e−107           20856 -  Homo sapiens , 837 aa.    1 . . . 195   192/195 (97%)           [WO200175067-A2, 11-OCT-2001]       ABG20865   Novel human diagnostic protein #    1 . . . 194   191/195 (97%)    e−107           20856 -  Homo sapiens , 837 aa.    1 . . . 195   192/195 (97%)           [WO200175067-A2, 11-OCT-2001]       ABB62623     Drosophila melanogaster     34 . . . 160   100/127 (78%)   8e−56           polypeptide SEQ ID NO 14661 -    4 . . . 130   116/127 (90%)             Drosophila melanogaster , 590 aa.           [WO200171042-A2, 27-SEP-2001]       ABB59840     Drosophila melanogaster     24 . . . 191   108/168 (64%)   5e−55           polypeptide SEQ ID NO 6312 -   14 . . . 158   122/168 (72%)             Drosophila melanogaster , 427 aa.           [WO200171042-A2, 27-SEP-2001]       ABG26810   Novel human diagnostic protein #   14 . . . 162   102/153 (66%)   5e−52           26801 -  Homo sapiens , 529 aa.   69 . . . 221   119/153 (77%)           [WO200175067-A2, 11-OCT-2001]                  
 
     [0338] In a BLAST search of public sequence datbases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7D.  
               TABLE 7D                          Public BLASTP Results for NOV7a                                         NOV7a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               I54276   PAX3A protein - human, 215 aa.   1 . . . 214   211/215 (98%)   e−120               1 . . . 215   212/215 (98%)       Q96H85   PAIRED BOX GENE 3   1 . . . 194   191/194 (98%)   e−108           (WAARDENBURG   1 . . . 194   192/194 (98%)           SYNDROME 1) -  Homo sapiens             (Human), 835 aa.       I68547   PAX3B protein - human, 206 aa.   1 . . . 196   193/197 (97%)   e−108               1 . . . 197   194/197 (97%)       AAF20054   PAX3-FORKHEAD FUSION   1 . . . 194   191/195 (97%)   e−107           PROTEIN -  Homo sapiens     1 . . . 195   192/195 (97%)           (Human), 836 aa.       Q9CXI6   PAIRED BOX GENE 3 -  Mus     1 . . . 194   191/195 (97%)   e−107             musculus  (Mouse), 479 aa.   1 . . . 195   192/195 (97%)                  
 
     [0339] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7E.  
               TABLE 7E                          Domain Analysis of NOV7a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV7a Match Region   for the Matched Region   Value               PAX   34 . . . 158   106/125 (85%)   1.1e−92               125/125 (100%)                  
 
     Example 8  
     [0340] The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A.  
               TABLE 8A                       NOV8 Sequence Analysis                                            SEQ ID NO:15   1305 bp        NOV8a,     GCCGCCAGCCCCGCCGAGGGGAGCCAGCGCCGTCTCTGAGGGGCGTCCGGCGCCGGAG                 CG102092-01     CC   ATG ACCCTCCGCCGACTCAGGAAGCTGCAGCAGAAGGAGGAGGCGGCGGCCACCCC               DNA Sequence   GGACCCCGCCGCCCGGACTCCCGACTCGGAAGTCGCGCCCGCCGCTCCGGTCCCGACC                   CCGGGACCCCCTGCCGCAGCCGCCACCCCTGGGCCCCCAGCGGACGAGCTGTACGCGG                   CGCTGGAGGACTATCACCCTGCCGAGCTGTACCGCGCGCTCGCCGTGTCCGGGGGCAC                   CCTGCCCCGCCGAAAGGGCTCAGGATTCCGCTGGAAGAATCTCAGCCAGAGTCCTGAA                   CAGCAGCGGAAAGTGCTGACGTTGGAGAAGGAGGATAACCAGACCTTCGGCTTTGAGA                   TCCAGACTTATGGCCTTCACCACCGGGAGGAGCAGCGTGTGGAAATGGTGACCTTTGT                   CTGCCGAGTTCATGAGTCTAGCCCTGCCCAGCTGGCTGGGCTCACACCAGGGGACACC                   ATCGCCAGCGTCAATGGCCTGAATGTGGAAGGCATCCGGCATCGAGAGATTGTGGACA                   TCATTAAGGCGTCAGGCAATGTTCTCAGACTGGAAACTCTATATGGGACATCAATTCG                   GAAGGCAGAACTGGAGGCTCGTCTGCAGTACCTGAAGCAAACCCTGTATGAGAAGTGG                   GGAGAGTACAGGTCCCTAATGGTGCAGGAGCAGCGGCTGGTGCATGGCCTGGTGGTGA                   AGGACCCCAGCATCTACGACACGCTGGAGTCGGTGCGCTCCTGCCTCTACGGCGCGGG                   CCTGCTCCCGGGCTCGCTGCCCTTCGGGCCTCTGCTCGCCGTGCCCGGGCGTCCCCGC                   GGAGGCGCCCGACGGGCCAGGGGCGACGCCGACGACGCCGTCTACCACACGTGCTTCT                   TCGGGGACTCCGAGCCGCCGGCGCTGCCGCCCCCGCCGCCCCCGGCCCGCGCCTTCGG                   CCCGGGCCCCGCCGAGACCCCTGCCGTGGGGCCGGGCCCTGGGCCGCGGGCCGCGCTG                   AGCCGCAGCGCCAGTGTGCGGTGCGCGGGCCCTGGCGGGGGCGGAGGCGGGGGCGCGC                   CGGGCGCGCTCTGGACTGAGGCTCGCGAGCAGGCCCTATGCGGCCCCGGCCTGCGCAA                   AACCAAGTACCGCAGCTTCCGCCGGCGGCTGCTCAAGTTCATCCCCGGACTCAACCGC                   TCCCTGGAGGAGGAGGAGAGCCAGCTG TAG   GGGCGGGGGCGGGCAGGGAGGTATTTAT                       TTATTTATTCGCAACAGCCAGCGCTAAAA                                       ORF Start: ATG at 61   ORF Stop: TAG at 1246           SEQ ID NO:16   395 aa MW at 42622.9 kD                     NOV8a,   MTLRRLRKLQQKEEAAATPDPAARTPDSEVAPAAPVPTPGPPAAAATPGPPADELYAA               CG102092-01   LEDYHPAELYRALAVSGGTLPRRKGSGFRWKNLSQSPEQQRKVLTLEKEDNQTFGFEI               Protein Sequence   QTYGLHHREEQRVEMVTFVCRVHESSPAQLAGLTPGDTIASVNGLNVEGIRHREIVDI                   IKASGNVLRLETLYGTSIRKAELEARLQYLKQTLYEKWGEYRSLMVQEQRLVHGLVVK                   DPSIYDTLESVRSCLYGAGLLPGSLPFGPLLAVPGRPRGGARRARGDADDAVYHTCFF                   GDSEPPALPPPPPPARAFGPGPAETPAVGPGPGPRAALSRSASVRCAGPGGGGGGGAP                   GALWTEAREQALCGPGLRKTKYRSFRRRLLKFIPGLNRSLEEEESQL                  
 
     [0341] Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.  
               TABLE 8B                       Protein Sequence Properties NOV8a                                        PSort   0.3600 probability located in mitochondrial matrix space;       analysis:   0.3000 probability located in microbody (peroxisome);           0.3000 probability located in nucleus;           0.2357 probability located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0342] A search of the NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8C.  
               TABLE 8C                          Geneseq Results for NOV8a                                         NOV8a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               AAU75901   Human modulator of GRIP-1 and    1 . . . 395   394/395 (99%)   0.0           arf activity (MGAA) -  Homo      1 . . . 395   395/395 (99%)             sapiens , 395 aa. [WO200200714-           A2, 03-JAN-2002]       ABG16389   Novel human diagnostic protein    3 . . . 176   118/189 (62%)   2e−50           #16380 -  Homo sapiens , 302 aa.   110 . . . 287    126/189 (66%)           [WO200175067-A2, 11-OCT-2001]       ABG16389   Novel human diagnostic protein    3 . . . 176   118/189 (62%)   2e−50           #16380 -  Homo sapiens , 302 aa.   110 . . . 287    126/189 (66%)           [WO200175067-A2, 11-OCT-2001]       AAB30608   Amino acid sequence of a human   71 . . . 394   129/333 (38%)   5e−47           B3-1 polypeptide -  Homo sapiens ,   45 . . . 358   186/333 (55%)           359 aa. [WO200075670-A1, 14-DEC-2000]       AAB58166   Lung cancer associated polypeptide   71 . . . 208    69/141 (48%)   2e−29           sequence SEQ ID 504 -  Homo     49 . . . 189    99/141 (69%)             sapiens , 251 aa. [WO200055180-           A2, 21-SEP-2000]                  
 
     [0343] In a BLAST search of public sequence datbases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8D.  
               TABLE 8D                          Public BLASTP Results for NOV8a                                         NOV8a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               CAD22389   SEQUENCE 1 FROM PATENT   1 . . . 395   394/395 (99%)   0.0           WO0200714 -  Homo sapiens     1 . . . 395   395/395 (99%)           (Human), 395 aa.       AAL87038   TAMALIN -  Rattus norvegicus     1 . . . 395   361/395 (91%)   0.0           (Rat), 394 aa.   1 . . . 394   366/395 (92%)       Q9JKL0   GRP1-ASSOCIATED SCAFFOLD   1 . . . 395   358/395 (90%)   0.0           PROTEIN GRASP -  Mus musculus     1 . . . 392   365/395 (91%)           (Mouse), 392 aa.       Q9JJA9   BRAIN CDNA, CLONE MNCB-   1 . . . 395   357/395 (90%)   0.0           4428, SIMILAR TO  MUS     1 . . . 392   364/395 (91%)             MUSCULUS  GRP1-ASSOCIATED           SCAFFOLD PROTEIN GRASP           MRNA -  Mus musculus  (Mouse),           392 aa.       CAC22473   SEQUENCE 1 FROM PATENT   71 . . . 394    129/333 (38%)   1e−46           WO0075670 -  Homo sapiens     45 . . . 358    186/333 (55%)           (Human), 359 aa.                  
 
     [0344] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8E.  
               TABLE 8E                          Domain Analysis of NOV8a                                     Identities/           Pfam   NOV8a   Similarities       Domain   Match Region   for the Matched Region   Expect Value               PDZ   101 . . . 189   30/92 (33%)   1.2e−10               69/92 (75%)                  
 
     Example 9  
     [0345] The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A.  
               TABLE 9A                       NOV9 Sequence Analysis                                                SEQ ID NO:17   3774 bp                     NOV9a,     TGGTTTTTGGTTTTTTTCTTTGATCATTATGAACATTGGCTTTTCACCCCTGAAGTGA                 CG102595-01     AA   ATG TTGAAAACTGAGTCTTCAGGTGAACGAACCACTCTCAGAAGTGCCTCTCCTCA               DNA Sequence   CAGGAATGCATATCGAACTGAGTTTCAGGCACTGAAAAGTACCTTTGACAAACCCAAG                   TCAGATGGGGAACAAAAAACAAAAGAAGGTGAGGGCTCCCAGCAGAGCAGGGGGAGGA                   AATATGGCTCCAATGTCAACAGAATTAAAAACCTATTTATGCAGATGGGTATGGAACC                   CAACGAGAATGCTGCAGTCATTGCCAAAACAAGGGGGAAAGGTGGACATTCATCTCCT                   CAGAGAAGAATGAAGCCCAAAGAATTTCTGGAAAAAACAGATGGCTCAGTTGTTAAGT                   TGGAGTCTTCTGTTTCTGAACGAATTAGTAGATTTGACACTATGTACGATGGCCCTTC                   ATATTCCAAGTTCACTGAGACTCGAAAGATGTTTGAGAGAAGTGTGCATGAATCAGGA                   CAGAACAACCGCTATTCCCCAAAGAAAGAGAAAGCTGGAGGGAGTGAACCTCAGGATG                   AATGGGGAGGTTCCAAGTCCAACAGAGGCAGTACTGATTCCTTGGACAGCCTTAGCTC                   CCGAACTGAGGCTGTCTCCCCAACTGTGAGTCAACTGAGTGCAGTATTTGAGAACACT                   GATTCTCCCAGTGCCATCATTTCTGAGAAGGCTGAAAACAATGAATACTCAGTGACTG                   GGCATTATCCCTTGAATTTACCATCTGTTACTGTTACAAATCTTGACACATTTGGTCA                   CCTGAAGGATTCTAATTCCTGGCCTCCTTCAAACAAGCGAGGTGTTGATACAGAGGAT                   GCTCACAAGAGTAATGCAACTCCAGTACCAGAAGTGGCTTCTAAAAGTACCTCTCTAG                   CTTCGATACCTGGTGAAGAGATCCAGCAGAGCAAGGAACCCGAGGACTCCACATCTAA                   TCAACAGACTCCCGACAGCATTGACAAAGATGGTCCTGAAGAACCTTGTGCTGAAAGT                   AAGGCAATGCCAAAGTCCGAAATCCCTTCACCACAAAGCCAACTGTTAGAAGATGCTG                   AAGCTAATTTGGTTGGAAGGGAGGCAGCAAAGCAACAGAGGAAAGAACTTGCAGGTGG                   TGATTTCACCTCTCCTGATGCTTCTGCATCCAGTTGTGGAAAAGAAGTACCTGAAGAT                   TCAAATAATTTTGATGGTTCCCATGTGTACATGCACAGTGACTATAATGTGTATAGGG                   TGAGATCCAGGTATAATTCAGACTGGGGAGAGACAGGCACTGAGCAGGATGAGGAGGA                   AGATAGTGATGAGAACAGTTACTATCAGCCTGATATGGAGTACTCGGAAATTGTTGGA                   TTGCCAGAAGAAGAAGAAATCCCAGCAAATAGGAAAATTAAGTTTAGTAGTGCTCCTA                   TTAAGGTTTTCAACACATACTCCAATGAAGACTATGACAGGAGAAATGACGAAGTTGA                   CCCTGTGGCTGCTTCAGCTGAGTATGAACTTGAAAAACGTGTAGAAAAGCTGGAACTT                   TTCCCAGTGGAGCTAGAGAAAGATGAGGATGGTCTTGGTATAAGTATTATTGGAATGG                   GTGTTGGAGCAGATGCTGGACTTGAAAAGCTGGGAATATTCGTCAAGACAGTAACAGA                   AGGTGGTGCTGCTCAACGGGATGGCAGAATACAAGTCAATGACCAGATTGTGGAAGTG                   GATGGAATCAGCTTGGTGGGTGTGACACAGAATTTTGCAGCAACAGTTCTCAGAAACA                   CCAAGGGCAACGTCAGATTTGTTATTGGGCGGGAAAAACCAGGACAAGTGAGCGAGGT                   TGCCCAGTTGATAAGCCAGACACTGGAACAGGAGAGGCGCCAGAGAGAGCTGCTGGAA                   CAGCACTATGCCCAGTATGATGCCGACGATGACGAGACAGGAGAATATGCCACAGATG                   AAGAAGAAGATGAGGTAGGACCTGTCCTTCCTGGCAGCGACATGGCCATTGAAGTCTT                   TGAGCTGCCTGAGAATGAGGACATGTTTTCCCCATCAGAACTGGACACAAGCAAGCTC                   AGTCACAAGTTCAAAGAGTTGCAAATCAAACATGCAGTTACAGAAGCAGAGATTCAAA                   AATTGAAGACCAAGCTGCAGGCAGCAGAAAATGAGAAAGTGAGGTGGGAACTAGAAAA                   AACCCAACTCCAACAAAACATAGAAGAGAATAAGGAAAGAATGTTGAAGTTGGAAAGC                   TACTGGATTGAGGCCCAAACATTATGCCACACAGTGAATGAGCATCTCAAAGAGACTC                   AAAGCCAGTATCAGGCCTTGGAAAAGAAATACAACAAGGCAAAGAAGTTGATCAAGGA                   TTTTCAACAAAAAGAGCTTGATTTCATCAAAAGACAGGAAGCAGAAAGAAAGAAAATA                   GAAGATTTGGAAAAAGCTCATCTTGTGGAAGTGCAAGGCCTCCAAGTGCGGATTAGAG                   ATTTGGAAGCTGAGGTATTCAGGCTACTGAAGCAAAATGGGACTCAAGTTAACAATAA                   TAACAACATCTTTGAGAGAAGAACATCTCTTGGTGAAGTCTCTAAAGGGGATACCATG                   GAGAACTTGGATGGCAAGCAGACATCTTGCCAAGATGGCCTAAGTCAAGACTTGAATG                   AAGCAGTCCCAGAGACAGAGCGCCTGGATTCAAAAGCACTGAAAACTCGAGCCCAGCT                   CTCTGTGAAGAACAGACGCCAGAGACCCTCTAGGACAAGACTGTATGATAGTGTTAGT                   TCCACAGATGGGGAGGACAGTCTAGAGAGAAAGAATTTTACCTTCAATGATGACTTCA                   GTCCCAGCAGTACCAGTTCAGCAGACCTCAGCGGCTTAGGAGCAGAACCTAAAACACC                   AGGGCTCTCTCAGTCCTTAGCACTGTCATCAGATGAGAGCCTGGATATGATAGATGAC                   GAGATCCTTGATGATGGACAGTCTCCCAAACACAGTCAGTGTCAGAATCGGGCCGTTC                   AGGAATGGAGTGTGCAGCAGGTTTCTCACTGGTTAATGAGCCTAAATCTGGAGCAGTA                   TGTATCTGAATTCAGTGCCCAAAACATCACTGGAGAACAGCTCCTGCAGTTGGATGGA                   AATAAACTTAAGGCTCTTGGAATGACAGCATCCCAGGACCGAGCAGTGGTCAAAAAGA                   AACTCAAGGAAATGAAGATGTCTCTAGAGAAGGCTCGGAAGGCCCAAGAGAAAATGGA                   AAAACAAAGAGAAAAGCTAAGGAGAAAGGAGCAAGAGCAAATGCAGAGGAAGTCCAAA                   AAGACAGAAAAGATGACGTCAACTACAGCCGAGGGTGCTGGTGAGCAG TAA   CACATAC                       CCTCTTACAGATGATGGAGATGCTCCAAGAGAAGTCCCCACCTCTTCCTGCCCTGCTC                       TCCTCCAGAGGATGAAAAAGAAACTAAATGATAAGGGTAATGCGGCTCTAGGCCGGCT                       GAGGAACTGTGTGTTGAATAACTGCATTTTCTGCAATAGAATGCACTCTTAATTTTAA                       CTACTAAAATAATCCCAAGCCACCTTTGGTTCATTAACAAACCAGAGATTTCATTTAA                       GTAGCTGTGTTTTGCTCTTCTCTAACTTACCAACATCTTGTGTTGTGTTGGGTGTGTT                       TTGTCACTTGGAGAACTAGTGTGACCCCACCCAAGAGCATGACACACCCTGGTGTTGT                       TAATGGAGCGCCGTGAATTTTCAGTGTGGGATCCTGAAATGGCAATTGCACATGTCTG                       CATG                                       ORF Start: ATG at 61   ORF Stop: TAA at 3355           SEQ ID NO:18   1098 aa MW at 123340.9 kD                     NOV9a,   MLKTESSGERTTLRSASPHRNAYRTEFQALKSTFDKPKSDGEQKTKEGEGSQQSRGRK               CG102595-01   YGSNVNRIKNLFMQMGMEPNENAAVIAKTRGKGGHSSPQRRMKPKEFLEKTDGSVVKL               Protein Sequence   ESSVSERISRFDTMYDGPSYSKFTETRKMFERSVHESGQNNRYSPKKEKAGGSEPQDE                   WGGSKSNRGSTDSLDSLSSRTEAVSPTVSQLSAVFENTDSPSAIISEKAENNEYSVTG                   HYPLNLPSVTVTNLDTFGHLKDSNSWPPSNKRGVDTEDAHKSNATPVPEVASKSTSLA                   SIPGEEIQQSKEPEDSTSNQQTPDSIDKDGPEEPCAESKAMPKSEIPSPQSQLLEDAE                   ANLVGREAAKQQRKELAGGDFTSPDASASSCGKEVPEDSNNFDGSHVYMHSDYNVYRV                   RSRYNSDWGETGTEQDEEEDSDENSYYQPDMEYSEIVGLPEEEEIPANRKIKFSSAPI                   KVFNTYSNEDYDRRNDEVDPVAASAEYELEKRVEKLELFPVELEKDEDGLGISIIGMG                   VGADAGLEKLGIFVKTVTEGGAAQRDGRIQVNDQIVEVDGISLVGVTQNFAATVLRNT                   KGNVRFVIGREKPGQVSEVAQLISQTLEQERRQRELLEQHYAQYDADDDETGEYATDE                   EEDEVGPVLPGSDMAIEVFELPENEDMFSPSELDTSKLSHKFKELQIKHAVTEAEIQK                   LKTKLQAAENEKVRWELEKTQLQQNIEENKERMLKLESYWIEAQTLCHTVNEHLKETQ                   SQYQALEKKYNKAKKLIKDFQQKELDFIKRQEAERKKIEDLEKAHLVEVQGLQVRIRD                   LEAEVFRLLKQNGTQVNNNNNIFERRTSLGEVSKGDTMENLDGKQTSCQDGLSQDLNE                   PSSTSSADLSGLGAEPKTPGLSQSLALSSDESLDMIDDEILDDGQSPKHSQCQNRAVQ                   EWSVQQVSHWLMSLNLEQYVSEFSAQNITGEQLLQLDGNKLKALGMTASQDRAVVKKK                   LKEMKMSLEKARKAQEKMEKQREKLRRKEQEQMQRKSKKTEKMTSTTAEGAGEQ                  
 
     [0346] Further analysis of the NOV9a protein yielded the following properties shown in Table 9B.  
               TABLE 9B                       Protein Sequence Properties NOV9a                                        PSort   0.8800 probability located in nucleus; 0.4472 probability       analysis:   located in mitochondrial matrix space; 0.3000 probability           located in microbody (peroxisome); 0.1362 probability located           in mitochondrial inner membrane       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0347] A search of the NOV9a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 9C.  
               TABLE 9C                          Geneseq Results for NOV9a                                         NOV9a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAW80359   An F-actin-combined protein    1 . . . 1093   984/1094 (89%)    0.0           amino acid sequence - Rattus sp,    1 . . . 1094   1032/1094 (93%)            1095 aa. [JP10276784-A, 20-OCT-1998]       AAU00022   Human activated T-lymphocyte   1 . . . 829   385/876 (43%)   e−173           associated sequence 1, ATLAS-1 -   1 . . . 783   500/876 (56%)             Homo sapiens , 862 aa.           [WO200114564-A2, 01-MAR-2001]       AAB42620   Human ORFX ORF2384   415 . . . 817    276/403 (68%)   e−157           polypeptide sequence SEQ ID   54 . . . 455    333/403 (82%)           NO: 4768 -  Homo sapiens , 460 aa.           [WO200058473-A2, 05-OCT-2000]       AAB36879   Murine Bau protein - Mus sp, 293   665 . . . 924    243/260 (93%)   e−135           aa. [US6140465-A, 31-OCT-2000]   1 . . . 260   251/260 (96%)       AAW44873   Murine BIN-1 Associated U1   665 . . . 924    243/260 (93%)   e−135           specific protein - Mus sp, 293 aa.   1 . . . 260   251/260 (96%)           [WO9808866-A1, 05-MAR-1998]                  
 
     [0348] In a BLAST search of public sequence datbases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9D.  
               TABLE 9D                          Public BLASTP Results for NOV9a                                         NOV9a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               O35867   Neurabin-I (Neural tissue-specific    1 . . . 1093   985/1094 (90%)    0.0           F-actin binding protein I) (Protein    1 . . . 1094   1033/1094 (94%)            phosphatase 1 regulatory subunit           9A) (p180) (PP1bp175) -  Rattus               norvegicus  (Rat), 1095 aa.       Q9ULJ8   Neurabin-I (Neural tissue-specific   357 . . . 1098     742/742 (100%)   0.0           F-actin binding protein I) (Protein   1 . . . 742    742/742 (100%)           phosphatase 1 regulatory subunit           9A) -  Homo sapiens  (Human), 742           aa (fragment).       O35274   Neurabin-II (Neural tissue-specific   1 . . . 826   411/862 (47%)   0.0           F-actin binding protein II) (Protein   1 . . . 817   516/862 (59%)           phosphatase 1 regulatory subunit           9B) (Spinophilin) (p130)           (PP1bp134) -  Rattus norvegicus             (Rat), 817 aa.       Q96SB3   NEURABIN II PROTEIN -  Homo     1 . . . 826   403/865 (46%)   0.0             sapiens  (Human), 817 aa.   1 . . . 817   524/865 (59%)       CAD28455   HYPOTHETICAL 47.0 KDA   415 . . . 826    279/412 (67%)   e−157           PROTEIN -  Homo sapiens     1 . . . 411   336/412 (80%)           (Human), 411 aa (fragment).                  
 
     [0349] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9E.  
               TABLE 9E                          Domain Analysis of NOV9a                                     Identities/           Pfam   NOV9a   Similarities       Domain   Match Region   for the Matched Region   Expect Value               PDZ   504 . . . 591    27/91 (30%)   1.5e−15               69/91 (76%)       SAM   986 . . . 1049   22/68 (32%)     1e−12               47/68 (69%)                  
 
     Example 10  
     [0350] The NOV10 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 10A.  
               TABLE 10A                       NOV10 Sequence Analysis                                                SEQ ID NO:19   435 bp                     NOV10a,     CCCACC   ATG GCCACAGTTCAGCAGCTGGAAGGAAGATGGCGCCTGGTGGACAGCGAAG               CG102744-01   GCTTTGATGAATACATGAAGGAGCTAGGAGGAATAGCTTTGCAAAAAATGGGCGCAAT               DNA Sequence   GGCCAAGCCAGATTGTATCATCACTTGTGATGGCAAAAACCTCACCATAAAAACTGAG                   AGCACTTTGAAAACAACACAGTTTTCTTGTACCCTGGGAGAGAAGTTTGAAGAAACCA                   CAGCTGATGGCAGAAAAACTCAGACTGTGTGCAACTTTACAGATGGTGCATTGGTTCA                   GCATCAGGAGTGGGATGGGAAGGAAAGCACAATAACAAGAACATTGAAAGATGGGAAA                   TTAGTGGTGGACTGTGTCATGAACCATGTCGCCTGTACTCGGATCTATGAAAAAGTAC                   AA TAA   AGATTCCATCATCACTTTGGACAG                                       ORF Start: ATG at 7   ORF Stop: TAA at 409           SEQ ID NO:20   134 aa MW at 14989.0 kD                     NOV10a,   MATVQQLEGRWRLVDSEGFDEYMKELGGIALQKMGAMAKPDCIITCDGKNLTIKTEST               CG102744-01   LKTTQFSCTLGEKFEETTADGRKTQTVCNFTDGALVQHQEWDGKESTITRTLKDGKLV               Protein Sequence   VDCVMNHVACTRIYEKVQ                  
 
     [0351] Further analysis of the NOV10a protein yielded the following properties shown in Table 10B.  
               TABLE 10B                       Protein Sequence Properties NOV10a                                        PSort   0.6500 probability located in cytoplasm; 0.1000 probability       analysis:   located in mitochondrial matrix space;           0.1000 probability located in lysosome (lumen); 0.0000           probability located in endoplasmic reticulum (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0352] A search of the NOV10a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10C.  
               TABLE 10C                          Geneseq Results for NOV10a                                         NOV10a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAU08674   Human keratinocyte fatty acid   1 . . . 134   127/135 (94%)   4e−70           binding protein, Mal1 -  Homo     1 . . . 135   132/135 (97%)             sapiens , 135 aa. [WO200160384-           A1, 23-AUG-2001]       AAR55866   Melanogenic inhibitor -  Homo     1 . . . 134   127/135 (94%)   4e−70             sapiens , 135 aa. [WO9412534-A,   1 . . . 135   132/135 (97%)           09-JUN-1994]       ABG27577   Novel human diagnostic protein   1 . . . 134   125/135 (92%)   9e−69           #27568 -  Homo sapiens , 158 aa.   24 . . . 158    130/135 (95%)           [WO200175067-A2, 11-OCT-2001]       ABG27577   Novel human diagnostic protein   1 . . . 134   125/135 (92%)   9e−69           #27568 -  Homo sapiens , 158 aa.   24 . . . 158    130/135 (95%)           [WO200175067-A2, 11-OCT-2001]       AAU08666   Human NOV10 protein -  Homo     1 . . . 134   114/135 (84%)   1e−60             sapiens , 134 aa. [WO200168851-   1 . . . 134   122/135 (89%)           A2, 20-SEP-2001]                  
 
     [0353] In a BLAST search of public sequence datbases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10D.  
               TABLE 10D                          Public BLASTP Results for NOV10a                                         NOV10a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q01469   Fatty acid-binding protein, epidermal   1 . . . 134   127/135 (94%)   9e−70           (E-FABP) (Psoriasis-associated fatty   1 . . . 135   132/135 (97%)           acid-binding protein homolog) (PA-           FABP) -  Homo sapiens  (Human),           135 aa.       P55052   Fatty acid-binding protein, epidermal   1 . . . 134   117/135 (86%)   8e−64           (E-FABP) (Differentiation-   1 . . . 135   128/135 (94%)           associated lipid binding protein LP2) -             Bos taurus  (Bovine), 135 aa.       P55053   Fatty acid-binding protein, epidermal   1 . . . 134   106/135 (78%)   6e−60           (E-FABP) (Cutaneous fatty acid-   1 . . . 135   125/135 (92%)           binding protein) (C-FABP) (DA11) -             Rattus norvegicus  (Rat), 135 aa.       Q05816   Fatty acid-binding protein, epidermal   1 . . . 134   103/135 (76%)   2e−59           (E-FABP) (Psoriasis-associated fatty   1 . . . 135   123/135 (90%)           acid-binding protein homolog) (PA-           FABP) (Keratinocyte lipid- binding           protein) -  Mus musculus  (Mouse),           135 aa.       MPRB2   myelin P2 protein - rabbit, 132 aa.   9 . . . 133    74/126 (58%)   9e−36               7 . . . 132    94/126 (73%)                  
 
     [0354] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10E.  
               TABLE 10E                          Domain Analysis of NOV10a                                 NOV10a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               lipocalin   6 . . . 133    38/157 (24%)   8.9e−26               100/157 (64%)                  
 
     Example 11  
     [0355] The NOV11 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11A.  
               TABLE 11A                       NOV11 Sequence Analysis                                                SEQ ID NO:21   4702 bp                     NOV11a,     CTCCTCTGTTTCCTGTGCAGTAGCTCCCGTTGCGGCGGCACCCGTGGCAGCCCTGGCG                 CG102801-01     GACGCAGGAGCG   ATG GCAGCGACCGATATAGCTCGCCAGGTGGGTGAAGGTTGCCGAA               DNA Sequence   CTGTCCCCCTGGCTGGACATGTGGGGTTTGACAGCTTGCCTGACCAGCTGGTGAATAA                   GTCCGTCAGCCAGGGCTTCTGCTTCAACATCCTGTGCGTGGGAGAGACAGGTTTGGGC                   AAGTCCACCCTCATGGACACCCTGTTCAACACCAAATTCGAAGGGGAGCCAGCCACCC                   ACACACAGCCGGGTGTCCAGCTCCAGTCTAATACCTATGACCTCCAAGAGAGCAACGT                   GAGGCTAAAGCTCACGATCGTTAGCACAGTTGGCTTTGGGGACCAGATCAACAAAGAG                   GACAGCTACAAGCCTATCGTGGAATTCATCGATGCACAATTCGAGGCCTACCTGCAGG                   AAGAGCTAAAGATCCGAAGAGTGCTACACACCTACCATGACTCCCGAATCCATGTCTG                   CTTGTATTTCATTGCCCCCACGGGTCATTCCCTGAAGTCTCTGGACCTAGTGACTATG                   AAGAAGCTGGACAGTAAGGTGAACATCATCCCCATCATTGCCAAAGCAGATGCCATTT                   CGAAGAGTGAGCTAACAAAGTTCAAAATCAAAATCACCAGCGAGCTTGTCAGCAACGG                   AGTCCAGATCTATCAGTTTCCTACAGATGATGAGTCGGTGGCAGAGATCAATGGAACC                   ATGAACGCCCACCTGCCGTTTGCTGTCATTGGCAGCACAGAAGAACTGAAGATAGGCA                   ACAAGATGATGAGGGCGCGGCAGTATCCTTGGGGCACTGTGCAGGTTGAAAACGAGGC                   CCACTGCGACTTTGTGAAGCTGCGGGAGATGCTGATTCGGGTCAACATGGAGGATCTG                   CGGGAGCAGACCCACACCCGGCACTATGAGCTGTATCGCCGCTGTAAGCTGGAGGAGA                   TGGGCTTCAAGGACACCGACCCTGACAGCAAACCCTTCAGTTTACAGGAGACATATGA                   GGCCAAAAGGAACGAGTTCCTAGGGGAACTCCAGAAAAAAGAAGAGGAGATGAGACAG                   ATGTTCGTCCAGCGAGTCAAAGAGAAAGAAGCGGAGCTCAAAGAGGCAGAGAAAGAGC                   TGCACGAGAAGTTTGACCGTCTGAAGAAACTGCACCAGGACGAGAAGAAGAAACTGGA                   GGATAAGAAGAAATCCCTGGATGATGAAGTGAATGCTTTCAAGCAAAGAAAGACGGCG                   GCTGAGCTGCTCCAGTCCCAGGGCTCCCAGGCTGGAGGCTCACAGACTCTGAAGAGAG                   ACAAAGAGAAGAAAAAT TAA   CTCTGCTGTTTGCTGCATGCTGCATGAGACCCAGGGTC                       CTGTTTGGGCTTCCTGTAGACACCCTTTTCCTGCGCAACAGAGCTGGGCCTCCCTTTC                       TCTAATTTCCCCCTTAACATGCCTGGGGGGCATACAATCCAACCCGCGCCCTCTCCTC                       TCTTCCTGCCAAGGTTTATAGAAACCTGAGAATCTGAGGGTGATGTCTGGCCGCTGGT                       CAAGAAGCCAACAGTCATGTGGCTCGCAGATGCATCCTGCATCCCAGTCCCCCTCCCA                       GCACCCCCAGCCATCCCCCCTGTCTTCCCCCACATCTTTGCCAGAGGTGTGACATGGT                       CAGGGGGCCCATCTGCTACTCTTTCCCACCAGCTCCCCTGTTCCAGTTCTGGTTGCTG                       TTAGTTTCCCTGAGGTATTTGCAACCACCATGGCTGGGTAACCACCGATCAGCACAGC                       TGTCCCCTTGGTCTCCTGTATCCCAGTCACTAGTCCTCCCTGGTCCACCCCACCCTCA                       TCCTCAGGAGCCACAGCCATTTCTTAGAGGGTTTCAAAAGGACAGCCTTTGGCGCCTT                       TTCCTTCTAACCTTTGAGTCCAGCCCTTTCCAGTTTTCATTCACTCGAAGTAACTGCA                       CTCAAGCTGTGCTCAAAATCGGCAACGCATTTATTTACACCAAGCCCTTCCCATAAAA                       CACAACTGCTGAAGAAAATAGCAGACGTTTCCCCTCTCTCTAACTCTGGGTATCCCAC                       AGATGCAAAAGGGAGAATAAACCTGAATATTATTACCAGCCTAGAGTCTTGAATGATA                       GCCTTACCGAATTCTTCTTGTGAGGTATTTCAGCATCTCGGGGGGTAATTTCCGGAAG                       GGCTCCATACTGTCCCAATAAGGTGAGGCCAGTAGCAGGAATAATAAATCCCACTTTG                       TAGGCTGGAAAACTGAGCTGTCAAAAGAATCAAGTGTTTGGGGGTTTGCTCTGATGAG                       TCTTCTAGTTCATTTGGTGAATGTCATGATGATTTTTAACATGCATTTTGCATGCATC                       CCCCAATAAGAAGAGATGAGACTCGGCCGGAGAGAAGAAAAGGCCCTTAACTTTCTTT                       CCAATTTAAGGAGTTGAGAGTTTAAAAATATTCCAGCCCTAAGTTTTTATCATGGGTC                       CCATCTGATAGTGGCTTTGGGAACCTCTGTGAAGTAGAGAGCCCTCCCTTGTCAGGGT                       TATGAGGCACAGTGGCCTTTGGTGTTTGGCCAGTGACAGTGTGAGAGATGGAGTTGAC                       CTGGCAATGATCTGTGGCTAACATGCCGTCTCTCTGCCCTTCCTTTGCAGTAATCCAT                       GGCTGTGTACTGAATAGTATTCCCCGCTACAGCTGGACTGGACTCCATTTAGCCTTTT                       AAGCCGAGGTTCCTATTTTAACTGACAGCTTTCCTTTGGGGTGCCAGGCAGCGAGGCC                       CCCCACCCCTATCCTGCCATGTACTTCAAGCTCACTTCTTCTTTTTGAGTTCCGCAAC                       TTGCTCCTGCCTCCCAGCCCCACTGGCACTGACCATGACCACCTACTTCTATTTTTTT                       TTTAGAGTTTCTTTTTTTGATCACTTACTTTCAAAGCACACAGTCAAACAAGGTTATG                       CCAAATTTCCAGGCCTTTTTGAAGTATTGAGAAGGGGAAGGGGATTTCTCACTTCAAT                       TATAGATCATAATAGGAAGCAAAAAGAAAAAAATGAAAAGCAAACATATGCACGCACT                       TTTCTTGTTGACAAAGCAAGAATGTAGGTTTGCTGTGTAGGTTTGGTGCTCTATTGAT                       TGGTGAGTGACCAGAGCAAGTATGAAGGTGATGCTGCCAAAGCACAAGCCTTTTTGAA                       GTATTGAGAAGGGGAAGGGGATTTCTCACTTCAATTATAGATCATAATAGGAAGCAAA                       AAGAAAAAAATGAAAAGCAAACATATGCACGCACTTTTCTTGTTGACAAAGCAAGAAT                       ATAGGTTTGCTGTGTAGGTTTGGTGCTCTATTGATTGGTGAGTGACCAGAGCAAGTAT                       GAAGGTGATGCTGCCAAAGCACAAGCCAGTTTCTTGGGAAAATTCAAGTTACAGTGGA                       GTATTTTTTTGAAGACCATATGCTTGGAGGTAGAAACAAACCAACGACCAAAAAAAAA                       AAAAAAAAAAAAATCTGCTCAGATACTCAGCCAGTAGCTCAGAGAGATGCTGAGTTAG                       GCCTGTCAGGTCTCCTTGGGAAAGGCTTCATATTTGCAACTTTGATGATTCTATGTCC                       AGCTTCAGAGCTGCTTTCCCAGAAATTCACGCTTAAACAACCAACCGGTAACCACCAC                       TTCCCCACACCGCCGCCCGGTAATTATTTGCATTACAAACCGGAGGCGCCCTCATTTG                       CATTTGTGTACAGATTAACTAGTTAAGGCTTGAGAAGCTCTGAATAATTCAAAAGTAT                       TAGACCCACACAGCCTTGGAGAGACCTTCAGAAACTAAGGAGGAGTTTTATATTAAGG                       GAGACATTTTAGTCAGTAAGACGATATAACCTACTTACTCCGTAAGGGGAAATGAAGG                       CCCGGAGAAGGGAAGGGACTTGACCGAGGTCCCACTTCTGTTTCGAGGCAGAAGCCAG                       ACTAATTTTCATGCCTCCTGACTCCCAATCAGTTTCACAAAGGGATTCAATCTGTTTA                       TATACGTTACATTCCTGGATACGAGGTCTTTTGATGTTCAGAGTAACTGACTAGTTAG                       TATTAGAAGACCCTCGAGGTTTTTTTCCACAGAAAAACATCTGAAGATGGATTGGGTG                       AGGGCTGGCAAAACGAAGGCATGCCGGGCCAGCTCCTTAACCCAATGACCCAGTGATG                       CTGCAAGGCTGGAACGGGGTCCAGGAGACTGTGTGTAACAGGTGCCCTAGGTGACCCT                       TATAATCAGGGAAGTTTGGTGAACAAAAATCGAACCCATGAGTGAACATAAATTAAAA                       AGTTGATCAACCTATTAAAATGTGTATTTCATTGGGTAGCTTTTCTCACTGTAGACAG                       ATTTTTTCCTTCTTCAATGAAAAGGCTTTTAAATTAGTACAACTGTTACTATTTAAAA                       AAAAAATACCCTAAGTACTCTGTTTACTTCTGGTGAAACAAAACCAGTCATTAGAAAT                       GGTCTGTGCTTTTATTTTCCCAGACTGGAGTGGCTTTTCTGAAACACACACACACACA                       CACACACACACACACACACACACACACGTACACACATCCCTCACTTCTCTTAAGCCAA                       GAAGTTTGCTTTCCCTAGCTGCAGTGTAGATGGCTCTTGTTTTTGTTTTTTTGTTTTA                       ATCATTTGGCATTCACATGTGGCTGTTAATATGTGCTTGTTTTTAATTAAAACAAGAA                       GCTT                                       ORF Start: ATG at 71   ORF Stop: TAA at 1352           SEQ ID NO:22   427 aa MW at 48872.3 kD                     NOV11a,   MAATDIARQVGEGCRTVPLAGHVGFDSLPDQLVNKSVSQGFCFNILCVGETGLGKSTL               CG102801-01   MDTLFNTKFEGEPATHTQPGVQLQSNTYDLQESNVRLKLTIVSTVGFGDQINKEDSYK               Protein Sequence   PIVEFIDAQFEAYLQEELKIRRVLHTYHDSRIHVCLYFIAPTGHSLKSLDLVTMKKLD                   SKVNIIPIIAKADAISKSELTKFKIKITSELVSNGVQIYQFPTDDESVAEINGTMNAH                   LPFAVIGSTEELKIGNKMMRARQYPWGTVQVENEAHCDFVKLREMLIRVNMEDLREQT                   HTRHYELYRRCKLEEMGFKDTDPDSKPFSLQETYEAKRNEFLGELQKKEEEMRQMFVQ                   RVKEKEAELKEAEKELHEKFDRLKKLHQDEKKKLEDKKKSLDDEVNAFKQRKTAAELL                   QSQGSQAGGSQTLKRDKEKKN                  
 
     [0356] Further analysis of the NOV11a protein yielded the following properties shown in Table 11B.  
               TABLE 11B                       Protein Sequence Properties NOV11a                                        PSort   0.8800 probability located in nucleus; 0.3000 probability       analysis:   located in microbody (peroxisome); 0.1000 probability           located in mitochondrial matrix space; 0.1000 probability           located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0357] A search of the NOV11a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 11C.  
               TABLE 11C                          Geneseq Results for NOV11a                                         NOV11a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAU21726   Novel human neoplastic disease   1 . . . 427   427/427 (100%)   0.0           associated polypeptide #159 -   24 . . . 450    427/427 (100%)             Homo sapiens , 452 aa.           [WO200155163-A1, 02-AUG-2001]       AAU21837   Novel human neoplastic disease   1 . . . 426   426/426 (100%)   0.0           associated polypeptide #270 -   52 . . . 477    426/426 (100%)             Homo sapiens , 478 aa.           [WO200155163-A1, 02-AUG-2001]       AAU18541   Human cytoskeletal element-   1 . . . 426   426/426 (100%)   0.0           related polypeptide #34 -  Homo     52 . . . 477    426/426 (100%)             sapiens , 478 aa. [WO200155168-           A1, 02-AUG-2001]       AAB93251   Human protein sequence SEQ ID   3 . . . 427   351/425 (82%)    0.0           NO: 12267 -  Homo sapiens , 429 aa.   2 . . . 425   386/425 (90%)            [EP1074617-A2, 07-FEB-2001]       AAB23260   Human cell division regulator   3 . . . 427   351/425 (82%)    0.0           HCDR-2 -  Homo sapiens , 425 aa.   2 . . . 425   386/425 (90%)            [US6121019-A, 19-SEP-2000]                  
 
     [0358] In a BLAST search of public sequence datbases, the NOV11a protein was found to have homology to the proteins shown in the BLASTP data in Table 11D.  
               TABLE 11D                          Public BLASTP Results for NOV11a                                             Identities/           Protein       NOV11a Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96A13   SEPTIN6 TYPE V (SEPTIN 2) -   1 . . . 427   427/427 (100%)   0.0             Homo sapiens  (Human), 429   1 . . . 427   427/427 (100%)           aa.       Q969W5   SEPTIN6 TYPE III -  Homo     1 . . . 427   427/427 (100%)   0.0             sapiens  (Human), 427 aa.   1 . . . 427   427/427 (100%)       Q14141   Septin 6 -  Homo sapiens     1 . . . 427   427/427 (100%)   0.0           (Human), 434 aa.   1 . . . 427   427/427 (100%)       Q96GR1   SIMILAR TO SEPTIN 6 -   1 . . . 427   426/427 (99%)    0.0             Homo sapiens  (Human), 434 aa.   1 . . . 427   426/427 (99%)        Q91XH2   SEPTIN 6 -  Mus musculus     1 . . . 427   411/427 (96%)    0.0           (Mouse), 427 aa.   1 . . . 427   420/427 (98%)                   
 
     [0359] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11E.  
               TABLE 11E                          Domain Analysis of NOV11a                                 NOV11a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               GTP_CDC   39 . . . 312   123/294 (42%)   8.4e−113               210/294 (71%)                  
 
     Example 12  
     [0360] The NOV12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12A.  
               TABLE 12A                       NOV12 Sequence Analysis                                                SEQ ID NO:23   4140 bp                     NOV12a,     GCCGCCGCTGCCAGTGGAGTTGCCTCCCCGCTTCCCTAGGGTGGTTCGGCTCCACCAA                 CG102899-01     AC   ATG TCGGCTCCTGTCGGGCCCCGGGGCCGCCTGGCTCCCATCCCGGCGGCCTCTCA               DNA Sequence   GCCGCCTCTGCAGCCCGAGATGCCTGACCTCAGCCACCTCACGGAGGAGGAGAGGAAA                   ATCATCCTGGCCGTCATGGATAGGCAGAAGAAAGAAGAGGAGAAGGAGCAGTCCGTGC                   TCAAAAAACTGCATCAGCAGTTTGAAATGTATAAAGAGCAGGTAAAGAAGATGGGAGA                   AGAATCACAGCAACAGCAAGAACAGAAGGGTGATGCGCCAACCTGTGGTATCTGCCAC                   AAAACAAAGTTTGCTGATGGATGTGGCCATAACTGTTCATATTGCCAAACAAAGTTCT                   GTGCTCGTTGTGGAGGTCGAGTGTCATTACGCTCAAACAAGGTTATGTGGGTATGTAA                   TTTGTGCCGAAAACAACAAGAAATCCTCACTAAATCAGGAGCATGGTTTTATAATAGT                   GGATCTAATACACCACAGCAACCTGATCAAAAGGTTCTTCGAGGGCTAAGAAATGAGG                   AGGCACCTCAGGAGAAGAAACCAAAACTACATGAGCAGACCCAGTTCCAAGGACCCTC                   AGGTGACTTATCTGTACCTGCAGTGGAGAAAAGTCGATCTCATGGGCTCACAAGACAG                   CATTCTATTAAAAATGGGTCAGGCGTGAAGCATCACATTGCCAGTGACATAGCTTCAG                   ACAGGAAAAGAAGCCCATCTGTGTCCAGAGATCAGAATAGAAGATACGACCAAAGGGA                   AGAAAGAGAGGAATATTCACAGTATGCTACTTCGGATACCGCAATGCCTAGATCTCCA                   TCAGATTATGCTGATAGGCGATCTCAACATGAACCTCAGTTTTATGAAGACTCTGATC                   ATTTAAGTTATAGGGACTCCAACAGGAGAAGTCATAGGCATTCCAAAGAATATATTGT                   AGATGATGAGGATGTGGAAAGCAGAGATGAATACGAAAGGCAAAGGAGAGAGGAAGAG                   TACCAGTCACGCTACCGAAGTGATCCGAATTTGGCCCGTTATCCAGTAAAGCCACAAC                   CCTATGAAGAACAAATGCGGATCCATGCTGAAGTGTCCCGAGCACGGCATGAGAGAAG                   GCATAGTGATGTTTCTTTGGCAAATGCTGATCTGGAAGATTCCAGGATTTCTATGCTA                   AGGATGGATCGACCATCAAGGCAAAGATCTATATCAGAACGTAGAGCTGCCATGGAAA                   ATCAGCGATCTTATTCAATGGAAAGAACTCGAGAGGCTCAGGGACCAAGTTCTTATGC                   ACAAAGGACCACAAACCATAGTCCTCCTACCCCCAGGAGGAGTCCACTACCCATAGAT                   AGACCAGACTTGAGGCGTACTGACTCACTACGGAAACAGCACCACTTAGATCCTAGCT                   CTGCTGTAAGAAAAACAAAACGGGAAAAAATGGAAACAATGTTAAGGAATGATTCTCT                   CAGTTCAGACCAGTCAGAGTCAGTGAGACCTCCACCACCAAAGCCTCATAAATCAAAG                   AAAGGCGGTAAAATGCGCCAGATTTCGTTGAGCAGTTCAGAGGAGGAATTGGCTTCCA                   CGCCTGAATATACAAGTTGTGATGATGTTGAGATTGAAAGTGAGAGTGTAAGTGAAAA                   AGGAGACATGGATTACAACTGGTTGGATCATACGTCTTGGCATAGCAGTGAGGCATCC                   CCAATGTCTTTGCACCCTGTAACCTGGCAACCATCTAAAGATGGAGATCGTTTAATTG                   GTCGCATTTTATTAAATAAGCGTCTAAAAGATGGAAGTGTACCTCGAGATTCAGGAGC                   AATGCTTGGCTTGAAGGTTGTAGGAGGAAAGATGACTGAATCAGGTCGGCTTTGTGCA                   TTTATTACTAAAGTAAAAAAAGGAAGTTTAGCTGATACTGTAGGACATCTTAGACCAG                   GTGATGAAGTATTAGAATGGAATGGAAGACTACTGCAAGGAGCCACATTTGAGGAAGT                   GTACAACATCATTCTAGAATCCAAACCTGAACCACAAGTAGAACTTGTAGTTTCAAGG                   CCTATTGGAGATATACCGCGAATACCTGATAGCACACATGCACAACTGGAGTCCAGTT                   CTAGCTCCTTTGAATCTCAAAAAATGGATCGTCCTTCTATTTCTGTTACCTCTCCCAT                   GAGTCCTGGAATGTTGAGGGATGTCCCACAGTTCTTATCAGGACAACTTTCAATAAAA                   CTATGGTTTGACAAGGTTGGTCACCAATTAATAGTTACAATTTTGGGAGCAAAAGATC                   TCCCTTCCAGGGAAGATGGGAGGCCAAGGAATCCTTATGTTAAAATTTACTTTCTTCC                   AGACAGAAGTGATAAAAACAAGAGAAGAACTAAAACAGTAAAGAAAACATTGGAACCC                   AAATGGAACCAAACATTCATTTATTCTCCAGTCCACCGAAGAGAATTTCGGGAACGAA                   TGCTAGAGATTACCCTTTGGGATCAAGCTCGTGTTCGAGAGGAAGAAAGTGAATTCTT                   AGGCGAGATTTTAATTGAATTAGAAACAGCATTATTAGATGATGAGCCACATTGGTAC                   AAACTTCAGACGCATGATGTCTCTTCATTGCCACTTCCCCACCCTTCTCCATATATGC                   CACGAAGACAGCTCCATGGAGAGAGCCCAACACGGAGGTTGCAAAGGTCAAAGAGAAT                   AAGTGATAGTGAAGTCTCTGACTATGACTGTGATGATGGAATTGGTGTAGTATCAGAT                   TATCGACATGATGGTCGAGATCTTCAAAGCTCAACATTATCAGTGCCAGAACAAGTAA                   TGTCATCAAACCACTGTTCACCATCAGGGTCTCCTCATCGAGTAGATGTTATAGGAAG                   GACTAGATCATGGTCACCCAGTGTCCCTCCTCCACAAAGTCGGAATGTGGAACAGGGG                   CTTCGAGGGACCCGCACTATGACCGGACATTATAATACAATTAGCCGAATGGACAGAC                   ATCGTGTCATGGATGACCATTATTCTCCAGATAGAGACAGGGATTGTGAAGCAGCAGA                   TAGACAGCCATATCACAGATCCAGATCAACAGAACAACGGCCTCTCCTTGAGCGGACC                   ACCACCCGCTCCAGATCCACTGAACGTCCTGATACAAACCTCATGAGGTCGATGCCTT                   CATTAATGACTGGAAGATCTGCCCCTCCTTCACCTGCCTTATCGAGGTCTCATCCTCG                   TACTGGGTCTGTCCAGACAAGCCCATCAAGTACTCCAGTCGCAGGACGAAGGGGCCGA                   CAGCTTCCACAGCTTCCACCAAAGGGAACGTTGGATAGAAAAGCAGGAGGTAAAAAAC                   TAAGGAGCACTGTCCAAAGAAGTACAGAAACAGGCCTGGCCGTGGAAATGAGGAACTG                   GATGACTCGACAGGCAAGCCGAGAGTCTACAGATGGTAGCATGAACAGCTACAGCTCA                   GAAGGAAATCTGATTTTCCCTGGTGTTCGCTTGGCCTCTGATAGCCAGTTCAGTGATT                   TCCTGGATGGCCTTGGCCCTGCTCAGCTAGTGGGACGCCAGACTCTGGCAACACCTGC                   AATGGGTGACATTCAGGTAGGAATGATGGACAAAAAGGGACAGCTGGAGGTAGAAATC                   ATCCGGGCCCGTGGCCTTGTTGTAAAACCAGGTTCCAAGACACTGCCAGCACCGTATG                   TAAAAGTGTATCTATTAGATAACGGAGTCTGCATAGCCAAAAAGAAAACAAAAGTGGC                   AAGAAAAACGCTGGAACCCCTTTACCAGCAGCTATTATCTTTCGAAGAGAGTCCACAA                   GGAAAAGTTTTACAGATCATCGTCTGGGGAGATTATGGCCGCATGGATCACAAATCTT                   TTATGGGAGTGGCCCAGATACTTTTAGATGAACTAGAGCTATCCAATATGGTGATCGG                   ATGGTTCAAACTTTTCCCACCTTCCTCCCTAGTAGATCCAACCTTGGCTCCTCTGACA                   AGAAGAGCTTCCCAATCATCTCTGGAAAGTTCAACTGGACCTTCTTACTCTCGTTCA T                       AG   CAGCTGTAAAAAAATTGTTGTCACAGCAACCAGCGTTACAAAAAAAAAAAAAAAAA                       AATCACAGGTTGCAACCCTGGT                                       ORF Start: ATG at 61   ORF Stop: TAG at 4060           SEQ ID NO:24   1333 aa MW at 151520.5 kD                     NOV12a,   MSAPVGPRGRLAPIPAASQPPLQPEMPDLSHLTEEERKIILAVMDRQKKEEEKEQSVL               CG102899-01   KKLHQQFEMYKEQVKKMGEESQQQQEQKGDAPTCGICHKTKFADGCGHNCSYCQTKFC               Protein Sequence   ARCGGRVSLRSNKVMWVCNLCRKQQEILTKSGAWFYNSGSNTPQQPDQKVLRGLRNEE                   APQEKKPKLHEQTQFQGPSGDLSVPAVEKSRSHGLTRQHSIKNGSGVKHHIASDIASD                   RKRSPSVSRDQNRRYDQREEREEYSQYATSDTAMPRSPSDYADRRSQHEPQFYEDSDH                   LSYRDSNRRSHRHSKEYIVDDEDVESRDEYERQRREEEYQSRYRSDPNLARYPVKPQP                   YEEQMRIHAEVSRARHERRHSDVSLANADLEDSRISMLRMDRPSRQRSISERRAAMEN                   QRSYSMERTREAQGPSSYAQRTTNHSPPTPRRSPLPIDRPDLRRTDSLRKQHHLDPSS                   AVRKTKREKMETMLRNDSLSSDQSESVRPPPPKPHKSKKGGKMRQISLSSSEEELAST                   PEYTSCDDVEIESESVSEKGDMDYNWLDHTSWHSSEASPMSLHPVTWQPSKDGDRLIG                   RILLNKRLKDGSVPRDSGAMLGLKVVGGKMTESGRLCAFITKVKKGSLADTVGHLRPG                   DEVLEWNGRLLQGATFEEVYNIILESKPEPQVELVVSRPIGDIPRIPDSTHAQLESSS                   SSFESQKMDRPSISVTSPMSPGMLRDVPQFLSGQLSIKLWFDKVGHQLIVTILGAKDL                   PSREDGRPRNPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYSPVHRREFRERM                   LEITLWDQARVREEESEFLGEILIELETALLDDEPHWYKLQTHDVSSLPLPHPSPYMP                   RRQLHGESPTRRLQRSKRISDSEVSDYDCDDGIGVVSDYRHDGRDLQSSTLSVPEQVM                   SSNHCSPSGSPHRVDVIGRTRSWSPSVPPPQSRNVEQGLRGTRTMTGHYNTISRMDRH                   RVMDDHYSPDRDRDCEAADRQPYHRSRSTEQRPLLERTTTRSRSTERPDTNLMRSMPS                   LMTGRSAPPSPALSRSHPRTGSVQTSPSSTPVAGRRGRQLPQLPPKGTLDRKAGGKKL                   RSTVQRSTETGLAVEMRNWMTRQASRESTDGSMNSYSSEGNLIFPGVRLASDSQFSDF                   LDGLGPAQLVGRQTLATPAMGDIQVGMMDKKGQLEVEIIRARGLVVKPGSKTLPAPYV                   KVYLLDNGVCIAKKKTKVARKTLEPLYQQLLSFEESPQGKVLQIIVWGDYGRMDHKSF                   MGVAQILLDELELSNMVIGWFKLFPPSSLVDPTLAPLTRRASQSSLESSTGPSYSRS                  
 
     [0361] Further analysis of the NOV12a protein yielded the following properties shown in Table 12B.  
               TABLE 12B                       Protein Sequence Properties NOV12a                                        PSort   0.9100 probability located in nucleus; 0.3000 probability       analysis   located in microbody (peroxisome); 0.1000 probability           located in mitochondrial matrix space; 0.1000 probability           located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0362] A search of the NOV12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12C.  
               TABLE 12C                          Geneseq Results for NOV12a                                         NOV12a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAB73488   Mouse Rim2, a novel isoform of     1 . . . 1097   1020/1184 (86%)    0.0           Rim -  Mus musculus , 1590 aa.     1 . . . 1182   1049/1184 (88%)            [EP1090986-A1, 11-APR-2001]       AAW29640   Human secreted protein   1079 . . . 1333   239/296 (80%)   e−124           C0618_1 -  Homo sapiens , 374    84 . . . 374   241/296 (80%)           aa. [WO9831802-A1, 23-JUL-1998]       AAB34848   Human secreted protein sequence   1096 . . . 1333   198/238 (83%)   e−110           encoded by gene 46 SEQ ID    1 . . . 237   218/238 (91%)           NO: 136 -  Homo sapiens , 237 aa.           [WO200058356-A1, 05-OCT-2000]       AAB34847   Gene 46 human secreted protein   1096 . . . 1333   197/238 (82%)   e−110           homologous amino acid sequence    1 . . . 237   218/238 (90%)           #135 -  Rattus norvegicus , 237 aa.           [WO200058356-A1, 05-OCT-2000]       ABB15089   Human nervous system related    983 . . . 1131   139/151 (92%)   2e−72            polypeptide SEQ ID NO: 3746 -    1 . . . 150   140/151 (92%)             Homo sapiens , 158 aa.           [WO200159063-A2, 16-AUG-2001]                  
 
     [0363] In a BLAST search of public sequence datbases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12D.  
               TABLE 12D                          Public BLASTP Results for NOV12a                                         NOV12a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9JIR7   RIM2-4C -  Rattus norvegicus     1 . . . 1333   1274/1333 (95%)   0.0           (Rat), 1330 aa.   1 . . . 1330   1301/1333 (97%)       Q9JHJ6   RIM2-5C (RIM2-2A) (RIM2-   1 . . . 1333   1274/1355 (94%)   0.0           3B) (RIM2-4A) -  Rattus     1 . . . 1352   1301/1355 (95%)             norvegicus  (Rat), 1352 aa.       Q9JIR9   RIM2-3A -  Rattus norvegicus     1 . . . 1333   1274/1371 (92%)    0.0           (Rat), 1368 aa.   1 . . . 1368   1301/1371 (93%)       Q9JIS0   RIM2-2B -  Rattus norvegicus     1 . . . 1333   1263/1402 (90%)   0.0           (Rat), 1399 aa.   1 . . . 1399   1289/1402 (91%)       Q9JIR8   RIM2-4B -  Rattus norvegicus     1 . . . 1333   1218/1333 (91%)   0.0           (Rat), 1292 aa.   1 . . . 1292   1247/1333 (93%)                  
 
     [0364] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12E.  
               TABLE 12E                          Domain Analysis of NOV12a                                 NOV12a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               RPH3A —      5 . . . 246   65/325 (20%)    0.017        effector       120/325 (37%)        PDZ   590 . . . 677   21/90 (23%)   0.00023               64/90 (71%)       C2   744 . . . 835   33/97 (34%)   9.6e−21               68/97 (70%)       C2   1194 . . . 1281   33/98 (34%)   1.4e−14               62/98 (63%)                  
 
     Example 13  
     [0365] The NOV13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13A.  
               TABLE 13A                       NOV13 Sequence Analysis                                                SEQ ID NO:25   1319 bp                     NOV13a,     CATGGGCCCGGGCGGTGCCCTCCATGCCCGGGGGATGAAGACACTGCTGCC   ATG GACA               CG105284-01   GCCCGTGCCAGCCGCAGCCCCTAAGTCAGGCTCTCCCTCAGTTACCAGGGTCTTCGTC               DNA Sequence   AGAGCCCTTGGAGCCTGAGCCTGGCCGGGCCAGGATGGGAGTGGAGAGTTACCTGCCC                   TGTCCCCTGCTCCCCTCCTACCACTGTCCAGGAGTGCCTAGTGAGGCCTCGGCAGGGA                   GTGGGACCCCCAGAGCCACAGCCACCTCTACCACTGCCAGCCCTCTTCGGGACGGTTT                   TGGCGGGCAGGATGGTGGTGAGCTGCGGCCGCTGCAGAGTGAAGGCGCTGCAGCGCTG                   GTCACCAAGGGGTGCCAGCGATTGGCAGCCCAGGGCGCACGGCCTGAGGCCCCCAAAC                   GGAAATGGGCCGAGGATGGTGGGGATGCCCCTTCACCCAGCAAACGGCCCTGGGCCAG                   GCAAGAGAACCAGGAGGCAGAGCGGGAGGGTGGCATGAGCTGCAGCTGCAGCAGTGGC                   AGTGGTGAGGCCAGTGCTGGGCTGATGGAGGAGGCGCTGCCCTCTGCGCCCGAGCGCC                   TGGCCCTGGACTATATCGTGCCCTGCATGCGGTACTACGGCATCTGCGTCAAGGACAG                   CTTCCTGGGGGCAGCACTGGGCGGTCGCGTGCTGGCCGAGGTGGAGGCCCTCAAACGG                   GGTGGGCGCCTGCGAGACGGGCAGCTAGTGAGCCAGAGGGCGATCCCACCGCGCAGCA                   TCCGTGGGGACCAGATTGCCTGGGTGGAAGGCCATGAACCAGGCTGTCGAAGCATTGG                   TGCCCTCATGGCCCATGTGGACGCCGTCATCCGCCACTGCGCAGGGCGGCTGGGCAGC                   TATGTCATCAACGGGCGCACCAAGGCCATGGTGGCGTGTTACCCAGGCAACGGGCTCG                   GGTACGTAAGGCACGTTGACAATCCCCACGGCGATGGGCGCTGCATCACCTGTATCTA                   TTACCTGAATCAGAACTGGGACGTTAAGGTGCATGGCGGCCTGCTGCAGATCTTCCCT                   GAGGGCCGGCCCGTGGTAGCCAACATCGAGCCACTCTTTGACCGGTTGCTCATTTTCT                   GGTCTGACCGGCGGAACCCCCACGAGGTGAAGCCAGCCTATGCCACCAGGTACGGCAT                   CACTGTCTGGTATTTTGATGCCAAGGAGCGGGCAGCAGCCAAAGACAAGTATCAGCTA                   GCATCAGGACAGAAAGGTGTCCAAGTACCTGTATCACAGCCGCCTACGCCCACC TAG   T                       GGCCAGTCCCAGAGCCGCATGGCAGACAGCTTAAATGACTTCA                                       ORF Start: ATG at 52   ORF Stop: TAG at 1273           SEQ ID NO:26   407 aa MW at 43635.9 kD                     NOV13a,   MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHCPGVPSEAS               CG105284-01   AGSGTPRATATSTTASPLRDGFGGQDGGELRPLQSEGAAALVTKGCQRLAAQGARPEA               Protein Sequence   PKRKWAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSGSGEASAGLMEEALPSAP                   ERLALDYIVPCMRYYGICVKDSFLGAALGGRVLAEVEALKRGGRLRDGQLVSQRAIPP                   RSIRGDQIAWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGSYVINGRTKAMVACYPGN                   GLGYVRHVDNPHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLL                   IFWSDRRNPHEVKPAYATRYGITVWYFDAKERAAAKDKYQLASGQKGVQVPVSQPPTP                   T                  
 
     [0366] Further analysis of the NOV13a protein yielded the following properties shown in Table 13B.  
               TABLE 13B                       Protein Sequence Properties NOV13a                                        PSort   0.3000 probability located in nucleus; 0.1818 probability       analysis   located in lysosome (lumen); 0.1000 probability           located in mitochondrial matrix space; 0.0000 probability           located in endoplasmic reticulum (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0367] A search of the NOV13a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13C.  
               TABLE 13C                          Geneseq Results for NOV13a                                         NOV13a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               ABG08029   Novel human diagnostic protein   114 . . . 388   161/280 (57%)   6e−88           #8020 -  Homo sapiens , 284 aa.    3 . . . 276   192/280 (68%)           [WO200175067-A2, 11-OCT-2001]       ABG08029   Novel human diagnostic protein   114 . . . 388   161/280 (57%)   6e−88           #8020 -  Homo sapiens , 284 aa.    3 . . . 276   192/280 (68%)           [WO200175067-A2, 11-OCT-2001]       AAB10873   Human tumor-associated antigen   175 . . . 388   132/215 (61%)   1e−80           9D7 protein -  Homo sapiens , 239    12 . . . 226   167/215 (77%)           aa. [DE19909503-A1, 07-SEP-2000]       ABB03740   Human musculoskeletal system   281 . . . 407   125/127 (98%)   6e−73           related polypeptide SEQ ID NO:    24 . . . 150   126/127 (98%)           1687 -  Homo sapiens , 150 aa.           [WO200155367-A1, 02-AUG-2001]       AAB63118   Human secreted protein sequence   281 . . . 388   106/108 (98%)   2e−61           encoded by gene 40 SEQ ID    1 . . . 108   107/108 (98%)           NO: 128 -  Homo sapiens , 108 aa.           [WO200061748-A1, 19-OCT-2000]                  
 
     [0368] In a BLAST search of public sequence datbases, the NOV13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13D.  
               TABLE 13D                          Public BLASTP Results for NOV13a                                         NOV13a   Identities/           Protein       Residues/   Similarities       Accession       Match   for the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96KS0   EGLN2 PROTEIN -  Homo     1 . . . 407   406/407 (99%)   0.0             sapiens  (Human), 407 aa.   1 . . . 407   406/407 (99%)       Q8WWY4   ESTROGEN-INDUCED TAG 6 -   1 . . . 407   405/407 (99%)   0.0             Homo sapiens  (Human), 407 aa.   1 . . . 407   405/407 (99%)       Q8VHJ1   EGLN2 -  Mus musculus  (Mouse),   1 . . . 407   369/421 (87%)   0.0           419 aa.   1 . . . 419   381/421 (89%)       Q99MI0   CELL GROWTH REGULATOR   1 . . . 407   368/421 (87%)   0.0           FALKOR -  Mus musculus     1 . . . 419   381/421 (90%)           (Mouse), 419 aa.       Q91YE2   EGLN2 PROTEIN -  Mus     1 . . . 407   362/421 (85%)   0.0             musculus  (Mouse), 419 aa.   1 . . . 419   373/421 (87%)                  
 
     [0369] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13E.  
               TABLE 13E                       Domain Analysis of NOV13a                                                Pfam   NOV13a   Identities/   Expect Value       Domain   Match Region   Similarities               for the Matched Region                  
 
     Example 14  
     [0370] The NOV14 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 14A.  
               TABLE 14A                       NOV14 Sequence Analysis                                                SEQ ID NO:27   2602 bp                     NOV14a,     TTCGGGTTCCAGACCCAAGGCTGCGTGTTCTCCACCGCTTGTTGTGGCCAGTGTTACT                 CG105444-01     GCGGTGACCGCCAGAGCAGCCTCGACGCT   ATG GAGGAGCCTGGTGCTACCCCTCAGCC               DNA Sequence   CTACCTGGGGCTGGTCCTGGAGGAGCTAGGCAGAGTTGTGGCAGCACTACCTGAGAGT                   ATGAGACCAGATGAGAATCCTTATGGTTTTCCATCGGAACTGGTGGTATGTGCAGCTG                   TTATTGGATTTTTTGTTGTTCTCCTTTTTTTGTGGAGAAGTTTTAGATCGGTTAGGAG                   TCGGCTTTATGTGGGAAGAGAGCAAAAACTTGGTGCAACGCTTTCTGGACTAATTGAA                   GAAAAATGTAAACTACTTGAAAAGTTTAGCCTTATTCAAAAAGAGTATGAAGGCTATG                   AAGTAGAGTCATCTTTAGAGGATGCCAGCTTTGAGAAGGCGGCAGCAGAAGAAGCACG                   AAGTTTGGAGGCAACCTGTGAAAAGCTGAGCAGGTCCAATTCTGAACTTGAGGATGAA                   ATCCTCTGTCTAGAAAAAGACTTAAAAGAAGAGAAATCTAAACATTCTCAACAAGATG                   AATTGATGGCGGATATTTCAAAAAGTATACAGTCTCTAGAAGATGAGTCAAAATCCCT                   CAAATCACAAATAGCTGAAGCCAAAATCATCTGCAAGACATTTAAAATGAGTGAAGAA                   CGACGGGCTATAGCAATAAAAGATGCTTTGAATGAAAATTCTCAACTTCAGACAAGCC                   ATAAACAGCTTTTTCAGCAAGAAGCTGAAGTATGGAAAGGACAAGTGAGTGAACTTAA                   TAAACAGAAAATAACATTTGAAGACTCCAAAGTACACGCAGAACAAGTTCTGAATGAT                   AAAGAAAATCACATCAAGACCCTGACTGGACACTTGCCAATGATGAAAGATCAGGCTG                   CTGTGCTTGAAGAAGACACAACGGATGATGATAACCTGGAATTAAAAGTGAACAGTCA                   ATGGGAAAATGGTGCTAACTTAGATGATCCTCCGAAAGGAGCTTTGAAGAAACTGATT                   CATGCTGCTAAGTTAAATGTTTCTTTAAAAAGCTTAGAAGGAGAAAGAAACCACATTA                   TTATTCAGTTATCTGAAGTGGACAAAACAAAGGAAGAGCTTACAGAGCATATTAAAAA                   TCTTCAGACTCAACAAGCATCTTTGCAATCAGAAAACATATATTTTGAAAGTGAGAAT                   CAGAAGCTTCAACAGAAACTTAAAATAATGACTGAATTCTATCAAGAAAATGAAATGA                   AACTCTACAGGAAATTAACAGTGGAGGAAAATTACCGAATAGAGGAAGAAGAGAAGCT                   TTCTAGAGTGGAAGAAAAGATCAGCCATGCCACTGAAGAGCTGGAGACCTATAGAAAG                   CTAGCCAAAGATCTTGAAGAAGAATTGGAGAGAACTGTTCATTTTTATCAAAAGCAGG                   TTATTTCCTACGAGAAAAGAGGACATGATAATTGGTTGGCAGCTCGGACTGCTGAAAG                   AAACCTCAGTGATTTAAGGAAAGAAAATGCTCACAACAAACAAAAATTAACTGAAAGA                   GAGTTGAAATTTGAACTTTTAGAAAAAGATCCTAATGCACTCGATGTTTCAAATACAG                   CATTTGGCAGAGAGCATTCCCCATGTAGTCCCTCACCATTGGGTCGGCCTTCATCTGA                   AACGAGAGCTTTTCCCTCTCCTCAAACTTTGTTGGAGGATCCACTCAGACTCTCACCT                   GTGCTTCCAGGGGGAGGAGGAAGAGGCCCAAGCAGCCCAGGGAATCCCCTGGACCATC                   AGATTACCAATGAAAGAGGAGAACCAAGCTATGACAGGTTAATCGATCCTCACAGGGC                   TCCTTCTGACACTGGGTCCCTGTCATCTCCGGTGGAACAGGACCGTAGGATGATGTTT                   CCTCCACCAGGGCAATCATATCCTGATTCAACTCTTCCTCCACAAAGGGAAGACAGAT                   TTTATTCTAATTCTGAAAGACTGTCTGGACCAGCAGAACCCAGAAGTTTTAAAATGAC                   TTCTTTGGATAAAATGGATAGGTCAATGCCTTCAGAAATGGAATCCAGTAGAAATGAT                   GCCAAAGATGATCTTGGTAATTTAAATGTGCCTGATTCATCTCTCCCTGCTGAAAATG                   AAGCAACTGGCCCTGGCCTTATTCCTCCACCTCTTGCTCCAATCAGCGGTCCATTGTT                   TCCAGTGGATACAAGGGGCCCATTCATGAGAAGAGGACCTCCTTTCCCCCCACCTCCT                   CCAGGAACCATGTTTGGAGCTTCTCGAGGTTATTTTCCACCAAGGGATTTCCCAGGTC                   CACCACATGCTCCATTTGCAATGAGAAACATCTATCCACCGAGGGGTTTACCTCCTTA                   CCTTCATCCGAGACCTGGATTTTACCCCAACCCCCCACATTCTGAAGGTAGAAGCGAG                   TTCCCTTCAGGATTGATTCCGCCTTCAAAGGAGCCTGCTACTGGACATCCAGAACCAC                   AGCAAGACACC TGA   CAATATTGTTGCTTTCTTCAAAAGTAATTTTGACTGATCTCATT                       TTCAGTTTAAGTAACTGCTGTTACTTAAGTGATTGCACTTTTCTCAAATT                                       ORF Start: ATG at 88   ORF Stop: TGA at 2506           SEQ ID NO:28   806 aa MW at 90996.1 kD                     NOV14a,   MEEPGATPQPYLGLVLEELGRVVAALPESMRPDENPYGFPSELVVCAAVIGFFVVLLF               CG105444-01   LWRSFRSVRSRLYVGREQKLGATLSGLIEEKCKLLEKFSLIQKEYEGYEVESSLEDAS               Protein Sequence   FEKAAAEEARSLEATCEKLSRSNSELEDEILCLEKDLKEEKSKHSQQDELMADISKSI                   QSLEDESKSLKSQIAEAKIICKTFKMSEERRAIAIKDALNENSQLQTSHKQLFQQEAE                   VWKGQVSELNKQKITFEDSKVHAEQVLNDKENHIKTLTGHLPMMKDQAAVLEEDTTDD                   DNLELKVNSQWENGANLDDPPKGALKKLIHAAKLNVSLKSLEGERNHIIIQLSEVDKT                   KEELTEHIKNLQTQQASLQSENIYFESENQKLQQKLKIMTEFYQENEMKLYRKLTVEE                   NYRIEEEEKLSRVEEKISHATEELETYRKLAKDLEEELERTVHFYQKQVISYEKRGHD                   NWLAARTAERNLSDLRKENAHNKQKLTERELKFELLEKDPNALDVSNTAFGREHSPCS                   PSPLGRPSSETRAFPSPQTLLEDPLRLSPVLPGGGGRGPSSPGNPLDHQITNERGEPS                   YDRLIDPHRAPSDTGSLSSPVEQDRRMMFPPPGQSYPDSTLPPQREDRFYSNSERLSG                   PAEPRSFKMTSLDKMDRSMPSEMESSRNDAKDDLGNLNVPDSSLPAENEATGPGLIPP                   PLAPISGPLFPVDTRGPFMRRGPPFPPPPPGTMFGASRGYFPPRDFPGPPHAPFAMRN                   IYPPRGLPPYLHPRPGFYPNPPHSEGRSEFPSGLIPPSKEPATGHPEPQQDT                  
 
     [0371] Further analysis of the NOV14a protein yielded the following properties shown in Table 14B.  
               TABLE 14B                       Protein Sequence Properties NOV14a                                        PSort   0.6000 probability located in endoplasmic reticulum       analysis:   (membrane); 0.3000 probability located           in microbody (peroxisome);           0.1000 probability located in mitochondrial inner membrane;           0.1000 probability located in plasma membrane       SignalP   Cleavage site between residues 69 and 70       analysis:                  
 
     [0372] A search of the NOV14a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14C.  
               TABLE 14C                          Geneseq Results for NOV14a                                         NOV14a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAM05968   Peptide #4650 encoded by probe   1 . . . 775   775/775 (100%)   0.0           for measuring breast gene   1 . . . 775   775/775 (100%)           expression -  Homo sapiens , 777 aa.           [WO200157270-A2, 09-AUG-2001]       AAM30846   Peptide #4883 encoded by probe   1 . . . 775   775/775 (100%)   0.0           for measuring placental gene   1 . . . 775   775/775 (100%)           expression -  Homo sapiens , 777 aa.           [WO200157272-A2, 09-AUG-2001]       AAM18368   Peptide #4802 encoded by probe   1 . . . 775   775/775 (100%)   0.0           for measuring cervical gene   1 . . . 775   775/775 (100%)           expression -  Homo sapiens , 777 aa.           [WO200157278-A2, 09-AUG-2001]       AAM58083   Human brain expressed single   1 . . . 775   775/775 (100%)   0.0           exon probe encoded protein SEQ   1 . . . 775   775/775 (100%)           ID NO: 30188 -  Homo sapiens ,           777 aa. [WO200157275-A2, 09-AUG-2001]       ABB22697   Protein #4696 encoded by probe   1 . . . 775   775/775 (100%)   0.0           for measuring heart cell gene   1 . . . 775   775/775 (100%)           expression -  Homo sapiens , 777 aa.           [WO200157274-A2, 09-AUG-2001]                  
 
     [0373] In a BLAST search of public sequence datbases, the NOV14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14D.  
               TABLE 14D                          Public BLASTP Results for NOV14a                                         NOV14a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               O95046   WUGSC: H_DJ0988G15.3   1 . . . 775    775/775 (100%)   0.0           PROTEIN (DJ1005H11.2)   1 . . . 775    775/775 (100%)           (WUGSC: H_DJ0988G15.3           PROTEIN) -  Homo sapiens             (Human), 777 aa.       O15320   Meningioma-expressed antigen   1 . . . 806   675/806 (83%)   0.0           6/11 (MEA6) (MEA11) -  Homo     1 . . . 804   721/806 (88%)             sapiens  (Human), 804 aa.       Q96SG9   BA500G10.2 (NOVEL PROTEIN   1 . . . 806   650/806 (80%)   0.0           SIMILAR TO MENINGIOMA   15 . . . 816    700/806 (86%)           EXPRESSED ANTIGEN 6           (MEA6) AND 11 (MEA11)) -             Homo sapiens  (Human), 825 aa           (fragment).       Q96RT6   CTAGE-2 -  Homo sapiens     30 . . . 787    590/758 (77%)   0.0           (Human), 754 aa.   1 . . . 754   641/758 (83%)       AAH26864   SIMILAR TO MENINGIOMA   30 . . . 804    536/785 (68%)   0.0           EXPRESSED ANTIGEN 6   1 . . . 778   612/785 (77%)           (COILED-COIL PROLINE-RICH) -             Mus musculus  (Mouse), 779 aa.                  
 
     [0374] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14E.  
               TABLE 14E                       Domain Analysis of NOV14a                                                Pfam   NOV14a   Identities/   Expect Value       Domain   Match Region   Similarities               for the Matched Region                  
 
     Example 15  
     [0375] The NOV15 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15A.  
               TABLE 15A                       NOV15 Sequence Analysis                                                SEQ ID NO:29   2614 bp                     NOV15a,     GGATTCGGGTTCCAGACCCAAGGCTGCGTGTTCTCCACCGTTTGTTGTGGCCAGTGTT                 CG105482-01     ACTGTGGTGACCGCCAGAGCAGCCTTCGCGCT   ATG GAGGAGCCCGGTGCTACCCCTCA               DNA Sequence   GCCCTACCTGGGGCTGGTCCTGGAGGAGCTACGCAGAGTTGTGGCAGCACTACCTGAG                   AGTATGACGGCAGATTCGAATCCTTATGGTTTTCCATGGGAACTGGTGGTATGTGCAG                   CTGTTGTTGGATTTTTTGTTGTTCTCCTTTTTTTGTGGAGAAGTTTTAGATCGGTTAG                   GAGTCGGCTTTATGTGGGAAGAGAGAAAAAACTTGGTGAAACGCTTTCTGGACTAATT                   GAAGAAAAATGTAAACTACTTGAAAAATTTAGCCTTATTCAAAAAGAGTATGAAGGCT                   ATGAAGTAGAGTCATCTTTAGAGGATGCCAGCTTTGAGAAGGCGGTAGCAGAAGCACG                   AAGTTTGGAGGCAACCTGTGAAAAGCTGAACAGGTCCAATTCTGAACTTGAGGATGAA                   ACCCTCTGTCTAGAAAAAGAGTTAAGGGAAATCAAATCTAAACATTCTCAACAAGATG                   AATTGATGGCGGATATTTCTAAAAGGATACAATCTCTAGAAGATGAGTCAAAATCCCT                   CAAATCACAAATAGCTGAAGCCAAAATCATCTGCAAGATTTTTCAAGCGACTGAAGAA                   CGATGGGCAATAGCAATAAAAGATGCTTTGAATAAAAATTCTCAACTTCACGAAAGCC                   AGAAACAGCTTTTGCAAGAAGCTGAAGTATGGAAAGAACAAGTGAGTGAACTTAATAA                   ACAGAAAATAACATTTGAAGACTCCAAAGTACATGCAGAACAAGTTCTAAATGATAAA                   ATCAATCACATCAAGACCCTGACTGGACACTTGCCAATGATGAACGATCAGGCTGCTG                   TGCTTGAAGAAGACACAACGGATGATGATAACTTGGAATTAGAAGTGAACAGTCAATC                   GGAAAATGGTGCTTATTTAGATGATCCTCCAAAAGGAGCTTTGAAGAAACTGATTCAT                   GCTGCTAAGTTAAATGTTTCTTTAAAAACCTTAGAAGGAGAAAGAAACCACATTATTA                   TTCAGTTATCTGAAGTGGACAAAACAAAGGAAGAGCTTACAGAGCATATTAAAAATCT                   TCAGACTCAACAAGCATCTTTGCAGTCAGAAAACATATATTTTGAAAGTGAGAATCAG                   AAGCTTCAACAGAAACTTAAAATAATGACTGAATTATATCAAGAAAATGAAATGACAC                   TCCACAGGAAATTGACAATAGAGGAAAATTACTGGATAGAGGAAGAAGAGAAGCTTTC                   TAAAGTGGAAGAAAAGATCAGCCATGCCACTGAAGAGCTGGAGACCTATAGAAAGCTA                   GCCAAAGATCTTGAAGAAGAATTGGAGAGAACTGTTCATTTTTATCAAAAGCAGGTTA                   TTTCCTACGAGAAAAAAGGACATGATAATTGGTTGGCAGCTCGGACTGCTGAAAGAAA                   CCTCAATGATTTAAGGAAAGAAAATGCTCACAACAAACAAAAATTAACTGAAACAGAG                   TTTAAATTTGAAGTTTTAGAAAAAGATCCTAATGCACTTGATGTTTCAAATACAGCAT                   CTGGCAGAGAGCATTCCCCATATGGTCCCTCACCATTGGGTCGGCCTTCATCTGAAAC                   GAGGACTTCTCTCTCCCCTCAAACTTTGTTGGAGGATCCACTCAGACTCTCACCTGTG                   CTTCCAGCGGGAGGAGGAAGAAGCCCAAGCGGCCGAGAGAATCCTCTGGACCATCAGA                   TTACCAATGAAAGAGGAGAACCAAGCTGTGATAGGTTAACTGATCCTCACAGAGCTCC                   TTCTGACACTGGGTCCCTGTCATCTCCATGGGAACAGGACCATAGGATGATGTTTCCT                   CCACCAGGACAATCATATCCTGATTCAGCTCTTCCTCCACAAAGGGAAGACAGATTTT                   ATTCTAATTCTGATAGACTGCCTGGACCATCAGAACTCAGAAGTTTTAATATGCCTTC                   TTTGGATAAAATGGATGGGTCAATGCCTTCAGAAATGGAATCCACTAGACATGATGCC                   AAAGATGATCCTGGTAGTTTAAATGTGCCTGATTCATCTCTCCCTGCTGAAAATGAAG                   CAACTGGCCCCGGCTTTATTCCTCCACCTCTTGCTCCAATCAGTGGTCCATTGTTTCC                   AGTGGACACAAGGTGCCCGTTCATGAGAAGAGGACCTCTTTTCCCCCAACCTCCTCCA                   GGAACGATGTTTGGAGCTTCACAAGGTTATTTTCCACCAAGGGATTTCCCAGGTCCAC                   CACATGTTCCATTTGCAATGAGAAACATCTGTCCACTGAGGGGTTTACCTCCTTACTT                   TCATCCAAGACCTGGATTTTACCCCAACCCCCCACATTCTGAAGGTAGAAGCGAGTTC                   CCTTCATGGTTGATTCTGCCTTTAAAGGAGCCTGCTACTGAACATCCAGAACCACAGC                   AAGAAACC TGA   CAATATTTTTGCTTTCTTCAAAAGTAATTTTGACTGATCTCATTTTC                       AGTTTAAGTAACTGCTGTTACTTAAGTGATTACACTTTTCTCAAATTGAAGTTTAATG                       GAAT                                       ORF Start: ATG at 91   ORF Stop: TGA at 2503           SEQ ID NO:30   804 aa MW at 91231.4 kD                     NOV15a,   MEEPGATPQPYLGLVLEELRRVVAALPESMTADSNPYGFPWELVVCAAVVGFFVVLLF               CG105482-01   LWRSFRSVRSRLYVGREKKLGETLSGLIEEKCKLLEKFSLIQKEYEGYEVESSLEDAS               Protein Sequence   FEKAVAEARSLEATCEKLNRSNSELEDETLCLEKELREIKSKHSQQDELMADISKRIQ                   SLEDESKSLKSQIAEAKIICKIFQATEERWAIAIKDALNKNSQLHESQKQLLQEAEVW                   KEQVSELNKQKITFEDSKVHAEQVLNDKINHIKTLTGHLPMMNDQAAVLEEDTTDDDN                   LELEVNSQSENGAYLDDPPKGALKKLIHAAKLNVSLKTLEGERNHIIIQLSEVDKTKE                   ELTEHIKNLQTQQASLQSENIYFESENQKLQQKLKIMTELYQENEMTLHRKLTIEENY                   WIEEEEKLSKVEEKISHATEELETYRKLAKDLEEELERTVHFYQKQVISYEKKGHDNW                   LAARTAERNLNDLRKENAHNKQKLTETEFKFEVLEKDPNALDVSNTASGREHSPYGPS                   PLGRPSSETRTSLSPQTLLEDPLRLSPVLPAGGGRSPSGRENPLDHQITNERGEPSCD                   RLTDPHRAPSDTGSLSSPWEQDHRMMFPPPGQSYPDSALPPQREDRFYSNSDRLPGPS                   ELRSFNMPSLDKMDGSMPSEMESTRHDAKDDPGSLNVPDSSLPAENEATGPGFIPPPL                   APISGPLFPVDTRCPFMRRGPLFPQPPPGTMFGASQGYFPPRDFPGPPHVPFAMRNIC                   PLRGLPPYFHPRPGFYPNPPHSEGRSEFPSWLILPLKEPATEHPEPQQET                  
 
     [0376] Further analysis of the NOV15a protein yielded the following properties shown in Table 15B.  
               TABLE 15B                       Protein Sequence Properties NOV15a                                        PSort   0.6000 probability located in endoplasmic       analysis:   reticulum (membrane);           0.3000 probability located in microbody (peroxisome);           0.1000 probability located in mitochondrial inner membrane;           0.1000 probability located in plasma membrane       SignalP   Cleavage site between residues 69 and 70       analysis:                  
 
     [0377] A search of the NOV15a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15C.  
               TABLE 15C                          Geneseq Results for NOV15a                                         NOV15a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               AAY77574   Human cytoskeletal protein   1 . . . 804   696/806 (86%)   0.0           (HCYT) (clone 3768043) -  Homo     1 . . . 806   731/806 (90%)             sapiens , 806 aa. [WO200006730-           A2, 10-FEB-2000]       AAM05968   Peptide #4650 encoded by probe for   1 . . . 773   694/775 (89%)   0.0           measuring breast gene expression -   1 . . . 775   716/775 (91%)             Homo sapiens , 777 aa.           [WO200157270-A2, 09-AUG-2001]       AAM30846   Peptide #4883 encoded by probe for   1 . . . 773   694/775 (89%)   0.0           measuring placental gene   1 . . . 775   716/775 (91%)           expression -  Homo sapiens , 777 aa.           [WO200157272-A2, 09-AUG-2001]       AAM18368   Peptide #4802 encoded by probe for   1 . . . 773   694/775 (89%)   0.0           measuring cervical gene expression -   1 . . . 775   716/775 (91%)             Homo sapiens , 777 aa.           [WO200157278-A2, 09-AUG-2001]       AAM58083   Human brain expressed single exon   1 . . . 773   694/775 (89%)   0.0           probe encoded protein SEQ ID NO:   1 . . . 775   716/775 (91%)           30188 -  Homo sapiens , 777 aa.           [WO200157275-A2, 09-AUG-2001]                  
 
     [0378] In a BLAST search of public sequence datbases, the NOV15a protein was found to have homology to the proteins shown in the BLASTP data in Table 15D.  
               TABLE 15D                          Public BLASTP Results for NOV15a                                         NOV15a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               O95046   WUGSC: H_DJ0988G15.3   1 . . . 773   694/775 (89%)   0.0           PROTEIN (DJ1005H11.2)   1 . . . 775   716/775 (91%)           (WUGSC: H_DJ0988G15.3           PROTEIN) -  Homo sapiens             (Human), 777 aa.       O15320   Meningioma-expressed antigen 6/11   1 . . . 804   672/804 (83%)   0.0           (MEA6) (MEA11) -  Homo sapiens     1 . . . 804   715/804 (88%)           (Human), 804 aa.       Q96SG9   BA500G10.2 (NOVEL PROTEIN   1 . . . 804   641/804 (79%)   0.0           SIMILAR TO MENINGIOMA   15 . . . 816    695/804 (85%)           EXPRESSED ANTIGEN 6 (MEA6)           AND 11 (MEA11)) -  Homo sapiens             (Human), 825 aa (fragment).       Q96RT6   CTAGE-2 -  Homo sapiens     30 . . . 782    592/753 (78%)   0.0           (Human), 754 aa.   1 . . . 751   643/753 (84%)       AAH26864   SIMILAR TO MENINGIOMA   30 . . . 802    532/783 (67%)   0.0           EXPRESSED ANTIGEN 6   1 . . . 778   609/783 (76%)           (COILED-COIL PROLINE-RICH) -             Mus musculus  (Mouse), 779 aa.                  
 
     [0379] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15E.  
               TABLE 15E                       Domain Analysis of NOV15a                                                Pfam   NOV15a   Identities/   Expect Value       Domain   Match Region   Similarities               for the Matched Region                  
 
     Example 16  
     [0380] The NOV16 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16A.  
               TABLE 16A                       NOV16 Sequence Analysis                                                SEQ ID NO:31   3813 bp                     NOV16a,     GCCCTGCCAACCCCCACC   ATG TGTGAGGTGATGCCCACAATCAATGAGGGGGACCTCT               CG105617-01   GGGGTCCCCTCCATGGCGCCGATGCTGACGCCAACTTCGAGCAGCTGATGGTGAACAT               DNA Sequence   GCTGGACGAGCGGGAGAAGTTGCTGGAGTCTCTTCGGGAGAGTCAGGAGACCTTGGCG                   GCCACACAGAGCCGGCTCCAGGATGCCATACACGAGCGGGACCAGCTCCAGCGCCACC                   TTAACTCCGCCCTCCCCCAGAATCCTGAAGCACTGAGGGGCCTTGGGGGTTTTCAGGA                   ATTTGCCACCTTAACCCGGGAGCTGAGCATGTGTCGGGAGCAGCTTCTAGAGCGGGAG                   GAAGAGATATCAGAACTGAAAGCAGAACGGAATAACACACGGCTGCTTCTGGAACATC                   TGGAGTGCCTGGTGTCCCGCCATGAACGGTCACTGCGGATGACTGTGGTGAAGCGCCA                   GGCCCAGTCACCTTCGGGGGTCTCCAGTGAGGTGGAGGTGCTGAAGGCCCTCAAGTCA                   CTGTTTGAGCACCACAAGGCCCTGGATGAGCAGGTGCGAGAGCGGCTCCGGGCAGCGC                   TGGAGCGAGTCACCACCTTGGAGGAGCAGCTGGCAGGTGCCCACCAGCAGGTAATCTG                   CCTGCTCACCCTCAGTCTGCAGCTCCTGGAAGTCCAGGCTGGTTCACCCCTGTGCCCT                   ACTCTGTTTCTTGTCAGATTTCTCCCTGCCATGGCTGGAAGCTGCCTGCTCACAGAGC                   TACTGTCCCTATCCCTGGAGGAGGATACGGGCCGGGTAGAGGAGCTGCAGGAGCTCCT                   GGAGAAGCAGAACTTTGAGTTGAGCCAGGCCCGGGAGCGACTGGTCACCCTAACAACA                   ACCGTGACTGAACTCGAGGAGGACCTGGGCACGGCCCGCCGGGACCTCATCAAGTCGG                   AGGAGCTGAGCAGCAAGCATCAGCGGGACCTCCGGGAGGCTCTGGCCCAGAAGGAGGA                   CATGGAAGAGCGGATTACTACACTGGAGAAGCGCTACCTGGCTGCTCAGCGTGAGGCA                   ACATCCATCCATGACCTCAATGACAAGCTGGAGAATGAGCTGGCCAACAAGGAGTCCC                   TGCACCGCCAGGTAGAGGAGAAGGCCCGACACCTGCAGGAGCTGCTGGAGGTGGCAGA                   GCAGAAGCTGCAGCAGACGATGCGCAAGGCAGAGACGCTGCCAGAGGTGGAGGCTGAG                   CTGGCCCAGAGAATTGCAGCCCTCACCAAGGCAGAAGAACGGCATGGCAACATTGAGG                   AGCACCTGCGGCAGCTGGAGGGACAGCTGGAGGAGAAGAACCAGGAGCTGGCACGGGT                   GAGGCAGCGGGAAAAGATGAATGAGGACCACAACAAGCGGCTGTCGGACACAGTGGAC                   CGGCTGCTCAGCGAGTCCAACGAGCGTCTGCAGCTCCACCTGAAGGAGCGCATGGCTG                   CCCTGGAGGAGAAGGTGCCCAGAGGGGCGGGGTTGGGATGCGAGAGGTTAGTGCTGGG                   TGTGGGGCGGGGGGAGGCGGGACTGCTGTCTGAAGAGATTGAGAAGCTGCGCCAAGAG                   GTGGACCAGCTGAAGGGCCGAGGGGGGCCGTTTGTGGATCATCACCGCTCAAGGTCGC                   ACATGGGCAGTGCAGCAGACGTGCGGTTCTCCCTGGGCACAACCACACACGCACCCCC                   AGGCGTGCATCGCCGCTACTCGGCATTGAGGGAAGAGTCTGCCAAGGTGAGGGGGTGG                   AGGGATCTCCTCAGGGAGTTTGGGGTCAATTCGGCCGACTGGGAGACTTCTCCACTGC                   CTGGGATGCTGGCCCCGGCAGCTGGCCCTGCCTTTGACAGTGACCCTGAGATCTCCGA                   CGTGGATGAGGATGAGCCAGGGGGTCTGGTGGGCTCTGCGGATGTTGTCTCCCCCAGC                   GGCCACTCAGATGCCCAGACCCTGGCCATGATGCTGCAGGAGCAGCTGGATGCCATCA                   ATGAGGAAATCAGGTTAATTCAGGAAGAGAAGGAGTCCACGGAGCTCCGCGCGGAGGA                   GATTGAGACGCGTGTAACCAGTGGCAGCATGGAAGCCCTAAACCTGAAGCAGCTGCGC                   AAGCGTGGTTCCATCCCCACCTCTCTGACGGCCCTGTCCCTGGCCAGCGCGTCCCCAC                   CACTCAGCGGCCGCTCCACACCTAAGCTCACCTCCCGCAGTGCTGCCCAGGACCTGGA                   CCGAATGGGGGTCATGACCCTGCCCAGTGACTTAAGAAAGCATAGGAGGAAGCTGCTG                   TCGCCAGTGTCTCGGGAAGAGAACCGAGAGGATAAAGCCACCATAAAATGTGAGACTT                   CTCCTCCTTCCTCACCCAGGACGCTGCGGCTAGAGAAGCTTGGCCACCCAGCCCTGAG                   CCAGGAAGAAGGCAAGAGTGCCTTGGAGGATCAGGGCAGCAACCCCAGCAGCAGCAAC                   AGCAGCCAGGACTCCCTGCACAAGGGCGCCAAGCGCAAGGGCATCAAGTCGTCCATTG                   GCCGCCTGTTTGGGAAGAAGGAGAAGGGCAGGCTGATCCAGCTGAGTCGGGATGGAGC                   CACAGGCCATGTTCTGCTAACAGACTCCGAATTCAGTATGCAGGAGCCTATGGTGCCT                   GCCAAGCTGGGGACCCAGGCAGAGAAGGACCGGCGGCTAAAGAAGAAACACCAGCTGC                   TTGAAGATGCCCGCAGGAAAGGAATGCCCTTTGCCCAGTGGGATGGTCCTACTGTGGT                   CTCCTGGTTGGAGCTCTGGGTGGGGATGCCTGCCTGGTATGTGGCAGCCTGCCGGGCC                   AACGTCAAGAGTGGTGCCATCATGTCCGCTCTGTCGGACACAGAGATCCAGCGGGAGA                   TCGGCATCAGCAATGCCCTGCACCGGCTCAAGCTCCGCCTGGCCATTCAGGAGATGGT                   GTCATTGACCAGCCCCTCTGCCCCACCCACCTCCAGGACTTCTTCTGGGAATGTCTGG                   GTCACCCATGAAGAGATGGAAACTCTGGAAACATCTACTAAAACAGACAGTGAGGAGG                   GCAGCTGGGCTCAGACCCTGGCCTATGGGGACATGAACCATGAGTGGATTGGGAATGA                   ATGGCTACCCAGCCTGGGGCTCCCGCAGTACCGCAGCTACTTCATGGAGTGCCTGGTG                   GACGCCCGCATGCTGGACCACCTCACCAAGAAGGACCTGCGGGTCCACCTGAAGATGG                   TGGACAGCTTCCATCGAACCAGTCTTCAGTATGGCATCATGTGTCTGAAGAGGCTGAA                   TTATGACCGGAAGGAGCTGGAGAAGAGGCGAGAGGAGAGCCAGCATGAGATCAAGGAT                   GTGTTAGTCTGGACCAACGACCAGGTGGTTCATTGGGTCCAGTCTATTGGGCTCCGGG                   ACTACGCAGGAAACCTGCATGAGAGTGGTGTGCATGGAGCCTTGCTGGCCCTGGACGA                   GAACTTCGACCACAACACACTGGCCCTGATCCTCCAGATCCCCACACAGAACACCCAG                   GCACGCCAAGTGATGGAAAGAGAGTTCAATAACCTGTTGGCCTTGGGCACAGACCGGA                   AGCTGGATGACGGGGATGACAAGGTGTTTCGCCGCGCGCCCTCCTGGAGGAAGCGCTT                   CCGGCCGCGGGAGCACCACGGTCGCGGCGGCATGCTCAGCGCTTCCGCGGAGACCCTC                   CCGGCGGGCTTCCGTGTGTCCACCCTGGGGACCCTGCAGCCCCCACCGGCCCCGCCAA                   AGAAGATCATGCCTGAAGCTCACTCCCACTATCTCTACGGACACATGCTCTCCGCCTT                   CCGGGAC TAG   CCATGGCCCCCAGGGCTGGCTTCCTCCTTCTGG                                       ORF Start: ATG at 19   ORF Stop: TAG at 3778           SEQ ID NO:32   1253 aa MW at 141282.1 kD                     NOV16a,   MCEVMPTINEGDLWGPLHGADADANFEQLMVNMLDEREKLLESLRESQETLAATQSRL               CG105617-01   QDAIHERDQLQRHLNSALPQNPEALRGLGGFQEFATLTRELSMCREQLLEREEEISEL               Protein Sequence   KAERNNTRLLLEHLECLVSRHERSLRMTVVKRQAQSPSGVSSEVEVLKALKSLFEHHK                   ALDEQVRERLRAALERVTTLEEQLAGAHQQVICLLTLSLQLLEVQAGSPLCPTLFLVR                   FLPAMAGSCLLTELLSLSLEEDTGRVEELQELLEKQNFELSQARERLVTLTTTVTELE                   EDLGTARRDLIKSEELSSKHQRDLREALAQKEDMEERITTLEKRYLAAQREATSIHDL                   NDKLENELANKESLHRQVEEKARHLQELLEVAEQKLQQTMRKAETLPEVEAELAQRIA                   ALTKAEERHGNIEEHLRQLEGQLEEKNQELARVRQREKMNEDHNKRLSDTVDRLLSES                   NERLQLHLKERMAALEEKVPRGAGLGCERLVLGVGRGEAGLLSEEIEKLRQEVDQLKG                   RGGPFVDHHRSRSHMGSAADVRFSLGTTTHAPPGVHRRYSALREESAKVRGWRDLLRE                   FGVNSADWETSPLPGMLAPAAGPAFDSDPEISDVDEDEPGGLVGSADVVSPSGHSDAQ                   TLAMMLQEQLDAINEEIRLIQEEKESTELRAEEIETRVTSGSMEALNLKQLRKRGSIP                   TSLTALSLASASPPLSGRSTPKLTSRSAAQDLDRMGVMTLPSDLRKHRRKLLSPVSRE                   ENREDKATIKCETSPPSSPRTLRLEKLGHPALSQEEGKSALEDQGSNPSSSNSSQDSL                   HKGAKRKGIKSSIGRLFGKKEKGRLIQLSRDGATGHVLLTDSEFSMQEPMVPAKLGTQ                   AEKDRRLKKKHQLLEDARRKGMPFAQWDGPTVVSWLELWVGMPAWYVAACRANVKSGA                   IMSALSDTEIQREIGISNALHRLKLRLAIQEMVSLTSPSAPPTSRTSSGNVWVTHEEM                   ETLETSTKTDSEEGSWAQTLAYGDMNHEWIGNEWLPSLGLPQYRSYFMECLVDARMLD                   HLTKKDLRVHLKMVDSFHRTSLQYGIMCLKRLNYDRKELEKRREESQHEIKDVLVWTN                   DQVVHWVQSIGLRDYAGNLHESGVHGALLALDENFDHNTLALILQIPTQNTQARQVME                   REFNNLLALGTDRKLDDGDDKVFRRAPSWRKRFRPREHHGRGGMLSASAETLPAGFRV                   STLGTLQPPPAPPKKIMPEAHSHYLYGHMLSAFRD                  
 
     [0381] Further analysis of the NOV16a protein yielded the following properties shown in Table 16B.  
               TABLE 16B                       Protein Sequence Properties NOV16a                                        PSort   0.9800 probability located in nucleus; 0.3000 probability       analysis:   located in microbody (peroxisome); 0.1000 probability located           in mitochondrial matrix space;           0.1000 probability located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0382] A search of the NOV16a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16C.  
               TABLE 16C                          Geneseq Results for NOV16a                                         NOV16a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAM38932   Human polypeptide SEQ ID NO   587 . . . 1253   666/667 (99%)   0.0           2077 -  Homo sapiens , 698 aa.   32 . . . 698   667/667 (99%)           [WO200153312-A1, 26-JUL-2001]       AAM38933   Human polypeptide SEQ ID NO   587 . . . 1253   657/667 (98%)   0.0           2078 -  Homo sapiens , 689 aa.   32 . . . 689   658/667 (98%)           [WO200153312-A1, 26-JUL-2001]       AAM40719   Human polypeptide SEQ ID NO   643 . . . 1253   609/611 (99%)   0.0           5650 -  Homo sapiens , 611 aa.    1 . . . 611   610/611 (99%)           [WO200153312-A1, 26-JUL-2001]       AAM40718   Human polypeptide SEQ ID NO   643 . . . 1253   609/611 (99%)   0.0           5649 -  Homo sapiens , 611 aa.    1 . . . 611   610/611 (99%)           [WO200153312-A1, 26-JUL-2001]       AAB94562   Human protein sequence SEQ ID   858 . . . 1237   371/380 (97%)   0.0           NO: 15337 -  Homo sapiens , 373    1 . . . 371   371/380 (97%)           aa. [EP1074617-A2, 07-FEB-2001]                  
 
     [0383] In a BLAST search of public sequence datbases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16D.  
               TABLE 16D                          Public BLASTP Results for NOV16a                                         NOV16a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               O75334   LIPRIN-ALPHA2 -  Homo     1 . . . 1220   831/1242 (66%)   0.0             sapiens  (Human), 1257 aa.   2 . . . 1227   982/1242 (78%)       S55553   LAR-interacting protein LIP1b -   1 . . . 1239   798/1274 (62%)   0.0           human, 1202 aa.   2 . . . 1185   948/1274 (73%)       Q13136   LAR-INTERACTING   1 . . . 1239   798/1274 (62%)   0.0           PROTEIN 1B -  Homo sapiens     2 . . . 1185   947/1274 (73%)           (Human), 1202 aa.       Q13135   LAR-INTERACTING   1 . . . 1234   798/1269 (62%)   0.0           PROTEIN 1A -  Homo sapiens     2 . . . 1180   945/1269 (73%)           (Human), 1185 aa.       O75145   KIAA0654 PROTEIN -  Homo     1 . . . 1240   736/1245 (59%)   0.0             sapiens  (Human), 1267 aa   75 . . . 1251    894/1245 (71%)           (fragment).                  
 
     [0384] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16E.  
               TABLE 16E                          Domain Analysis of NOV16a                                     Identities/           Pfam   NOV16a   Similarities       Domain   Match Region   for the Matched Region   Expect Value               SAM   895 . . . 961   16/68 (24%)   0.84               36/68 (53%)       SAM   1010 . . . 1074   22/68 (32%)   3.6e−11               47/68 (69%)                  
 
     Example 17  
     [0385] The NOV17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A.  
               TABLE 17A                       NOV17 Sequence Analysis                                                SEQ ID NO:33   1245 bp                     NOV17a,     GCCCAAAAAGGCCATGTGCCTGTGCTGGCGTTCATA   ATG GAGGACCTGGAGGATGTGG               CG105638-01   CCCTGGACCACGTAGACAAGCTGGGGAGGACGGCGTTTCACAGGGCAGCTGAGCACGG               DNA Sequence   GCAGCTGGATGCTCTGGACTTCCTCGTGGGCTCTGGCTGTGACCACAATGTCAAAGAC                   AAGGAGGGGAACACTGCCCTTCATCTGGCTGCTGGTCGGGGCCATATGGCTGTGCTGC                   AGCGACTTGTGGACATCGGGCTGGACCTGGAGGAGCAGAATGCGGAAGGTCTGACTGC                   CCTGCATTCGGCTGCTGGAGGATCCCACCCTGACTGTGTGCAGCTCCTCCTCAGGGCT                   GGGAGCACCGTGAATGCCCTCACCCAGAAAAACCTAAGCTGCCTTCACTATGCAGCCC                   TCAGTGGCTCGGAGGATGTGTCTCGGGTCCTCATCCACGCAGGAGGCTGCGCCAACGT                   GGTTGATCATGGTGCCTCTCCTCTGCACCTCGCTGTGAGGCACAACTTCCCTGCCTTG                   GTCCGGCTCCTCATCAACTCCGACAGTGACGTGAATGCCGTGGACAATAGGCAGCAGA                   CGCCCCTTCACCTGGCTGCAGAGCACGCCTGGCAGGACATAGCAGATATGCTCCTCAT                   TGCTGGGGTTGACTTAAACCTGAGAGATAAGCAGGGAAAAACCGCCCTGGCAGTGGCT                   GTCCGCAGCAACCATGTCAGCCTGGTGGACATGATCATAAAAGCTGATCGTTTCTACA                   GATGGGAGAAGACCACCCCAGTGATCCCTCTGGGAAGAGCTTGTCCTTTAAGCAGGAC                   CATCGGCAGGAAACACAGCAGCTCCGTTCTGTGCTGTGGCGGCTGGCCTCCAGGTATC                   TGCAGCCCCGTGAGTGGAAGAAGCTGGCATATTCCTGGGAGTTCACGGAGGCACATGT                   CGACGCCATCGAGCAACAGTGGACAGGCACCAGGAGCTATCAGGAGCACGGCCACCGA                   ATGCTGCTCATTTGGCTGCATGGCGTGGCCACGGCTGGTGAGAACCCCAGCAAAGCGC                   TGTTCGAGGGCCTCGTGGCCATTGGCAGGAGGGACCTGGCTGGTAAGAGCGTACTCTG                   CTGGGCTGCTTCTCAGGAGCTGGGTGGCCCCCACTGGAATGCAGCAGGGCCCTCCAAG                   GGCTGCTCAGACAAGAATGCTG TGA   TGCTGGCTCTAGGCCTTCCAGATTCCTACCCCT                       AGCCCTGCCCTCTTTTCCCTTGGGCAA                                       ORF Start: ATG at 37   ORF Stop: TGA at 1183           SEQ ID NO:34   382 aa MW at 40940.2 kD                     NOV17a,   MEDLEDVALDHVDKLGRTAFHRAAEHGQLDALDFLVGSGCDHNVKDKEGNTALHLAAG               CG105638-01   RGHMAVLQRLVDIGLDLEEQNAEGLTALHSAAGGSHPDCVQLLLRAGSTVNALTQKNL               Protein Sequence   SCLHYAALSGSEDVSRVLIHAGGCANVVDHGASPLHLAVRHNFPALVRLLINSDSDVN                   AVDNRQQTPLHLAAEHAWQDIADMLLIAGVDLNLRDKQGKTALAVAVRSNHVSLVDMI                   IKADRFYRWEKTTPVIPLGRACPLSRTIGRKHSSSVLCCGGWPPGICSPVSGRSWHIP                   GSSRRHMSTPSSNSGQAPGAIRSTATECCSFGCMAWPRLVRTPAKRCSRASWPLAGGT                   WLVRAYSAGLLLRSWVAPTGMQQGPPRAAQTRML                  
 
     [0386] Further analysis of the NOV17a protein yielded the following properties shown in Table 17B.  
               TABLE 17B                       Protein Sequence Properties NOV17a                                        PSort   0.6500 probability located in cytoplasm;       analysis:   0.2403 probability located in lysosome (lumen);           0.1000 probability located in mitochondrial matrix space;           0.0000 probability located in endoplasmic reticulum           (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0387] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17C.  
               TABLE 17C                          Geneseq Results for NOV17a                                         NOV17a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAU19570   Human diagnostic and therapeutic   14 . . . 156   121/144 (84%)   3e−60           polypeptide (DITHP) #156 -   19 . . . 162   124/144 (86%)             Homo sapiens , 162 aa.           [WO200162927-A2, 30-AUG-2001]       AAM93683   Human polypeptide, SEQ ID NO:    1 . . . 113    113/113 (100%)   8e−60           3580 -  Homo sapiens , 129 aa.    1 . . . 113    113/113 (100%)           [EP1130094-A2, 05-SEP-2001]       AAO02579   Human polypeptide SEQ ID NO   16 . . . 243    83/231 (35%)   1e−33           16471 -  Homo sapiens , 266 aa.   21 . . . 251   128/231 (54%)           [WO200164835-A2, 07-SEP-2001]       AAU03539   Human protein kinase #39 -  Homo      5 . . . 234    78/232 (33%)   6e−28             sapiens , 832 aa. [WO200138503-   574 . . . 804    127/232 (54%)           A2, 31-MAY-2001]       ABB53291   Human polypeptide #31 -  Homo      5 . . . 234    77/232 (33%)   1e−27             sapiens , 784 aa. [WO200181363-   526 . . . 756    127/232 (54%)           A1, 01-NOV-2001]                  
 
     [0388] In a BLAST search of public sequence datbases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17D.  
               TABLE 17D                          Public BLASTP Results for NOV17a                                         NOV17a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9GKW8   HYPOTHETICAL 40.3 KDA    1 . . . 243   229/243 (94%)   e−131           PROTEIN -  Macaca fascicularis      1 . . . 243   238/243 (97%)           (Crab eating macaque)           (Cynomolgus monkey), 366 aa.       AAH27350   HYPOTHETICAL 14.0 KDA   15 . . . 113    76/105 (72%)   5e−32           PROTEIN -  Homo sapiens     13 . . . 117    82/105 (77%)           (Human), 133 aa (fragment).       Q8YTG9   HYPOTHETICAL PROTEIN   22 . . . 233    75/214 (35%)   2e−27           ALL2748 - Anabaena sp. (strain   10 . . . 223   124/214 (57%)           PCC 7120), 426 aa.       Q96KH0   PROBABLE DUAL-    5 . . . 234    78/232 (33%)   2e−27           SPECIFICITY SER/THR/TYR   526 . . . 756    127/232 (54%)           KINASE -  Homo sapiens             (Human), 784 aa.       Q9NTA1   HYPOTHETICAL 42.9 KDA    5 . . . 234    78/232 (33%)   2e−27           PROTEIN -  Homo sapiens     139 . . . 369    127/232 (54%)           (Human), 397 aa (fragment).                  
 
     [0389] PFam analysis predicts that the NOV17a protein contains the domains shown in the Table 17E.  
               TABLE 17E                          Domain Analysis of NOV17a                                             Identities/                       Similarities           Pfam   NOV17a Match   for the Matched   Expect           Domain   Region   Region   Value                       ank   15 . . . 47   14/33 (42%)   2.7e−06                   25/33 (76%)           ank   48 . . . 80   13/33 (39%)   3.3e−06                   25/33 (76%)           ank    81 . . . 113   16/33 (48%)   2.2e−07                   24/33 (73%)           ank   114 . . . 146   11/33 (33%)   0.0005                   26/33 (79%)           ank   147 . . . 178   15/33 (45%)   0.00017                   26/33 (79%)           ank   179 . . . 211   16/33 (48%)   2.6e−06                   26/33 (79%)                      
 
     Example 18  
     [0390] The NOV18 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 18A.  
               TABLE 18A                       NOV18 Sequence Analysis                                                SEQ ID NO:35   5650 bp                     NOV18a,     ATG GCCCCTTCTGAGACTGCTCGGAAGTGGGAGAGGATGCTTGCCCTTACGGGTGTTC               CG105671-01   TGCCCCTGAGACTGGCGCCCCTTGGTGCTCCCTCTGTTCCCTCCCAGATCTTGGGAGA               DNA Sequence   AGCACGGACATCTCTGTTTCTGCTTTTGGTCCCCGAACGCAGTTACGCGCCCACTGGC                   TCCCTGTCTCTGGCGCTTCTGGGCACGGGGGAGCTGGGGCGGCCCCGCCTGCGCACGG                   CGGACAAGCTGACCGGGTCTCTGAGGCGCGGGGGGAGATGCCTGAAGCGGCAGGGCGG                   CGGCGTGGGCACCATCCTGAGCAATGTGCTCAAGAAGCGCAGCTGCATTTCCCGGACC                   GCGCCCCGGCTGCTGTGCACCCTGGAGCCGGGCCGGGGAGCTCTGGGGAAAGTCCGCG                   TGCCACCTGGTGCGGGGCACCGCGTTGGCACCTGCAGGGAGCGATTGGTCTGGAAGGG                   CTCGCAGGAAGCCAGACCTTGCGAGAGGTGTGTGGGGGCGGAGAGTGGCACAGGTTTG                   ACACTGCAGGTCGGAGGAGGAAGACAGTGGCTGCAAAGGCAAAATCGGGTGTTATTTT                   CCCAAGAGTCCCTTCAGCGTGAGTGCCGGGGTCAGCTCGAACTGGAGCCTGTAATTTG                   TGAGTGCGAGTGGGGAGCAGCAGGAGATCCTTTTCATAGACTGCATAACTCCGTGTCG                   GCTCCATCACCCGGCATCCCTCCCCGGGATTTTAAGAGCCTGGCCCTAGCGCGGGCTC                   CTGGGCACGGAGGTTTCTGGCAAGGAGTGGCTGCAGAGGGAGTTGGCTGTACTCTCAC                   TGGTGCTTGGCGCTCACCTGTTCCCTGGAGTGGCACCGGCTGCGTTCCAGGCGGGTTC                   ACGGTCCCCGGCCCCCGCCCCCCAGCGCCAGCGCCTTGGGGACCTGCTGTAGAGCCGC                   AGGAGAATCGAGCTGCAGAGTCCCTGCCTGCTTGCAGGCTGTGTCACAGAAGAGAACA                   TGGCAGAACAGTATGCTCAGGAGTTGATACCAAGTTGAAATTCACTCTTGAGCCATCT                   TTAGGTCAAAATGGTTTTCAGCAGTGGTACGATGCTCTCAAGGCAGTTGCCAGGCTAT                   CCACAGGAATACCAAAGGAATGGAGGAGAAAGGTTTGGTTGACCTTGGCAGATCATTA                   TTTGCACAGTATAGCCATTGACTGGGACAAAACCATGCGCTTCACTTTCAATGAAAGG                   AGTAATCCTGATGATGACTCCATGGGAATTCAGATAGTCAAGGACCTTCACCGCACAG                   GCTGTAGTTCTTACTGTGGCCAGGAGGCTGAGCAGGACAGGGTTGTGTTGAAGCGGGT                   GCTGCTGGCCTATGCCCGATGGAACAAAACTGTTGGGTACTGCCAAGGCTTTAACATC                   CTGGCTGCACTAATTCTGGAAGTGATGGAAGGCAATGAAGGGGATGCCCTGAAAATTA                   TGATTTACCTTATTGATAAGGTACTTCCCGAAAGCTATTTCGTCAATAATCTCCGGGC                   ATTGTCTGTGGATATGGCTGTCTTCAGAGACCTTTTAAGAATGAAGCTGCCGGAATTA                   TCTCAGCACCTGGATACTCTTCAGAGAACTGCAAACAAAGAAAGTGGAGGTGGATATG                   AGCCCCCACTTACAAATGTCTTCACGATGCAGTGGTTTCTGACTCTCTTTGCCACATG                   CCTCCCTAATCAGACCGTTTTAAAGATCTGGGATTCAGTCTTCTTTGAAGGTTCAGAA                   ATCATCCTAAGGGTGTCGCTGGCTATCTGGGCAAAATTAGGAGAGCAGATAGAATGTT                   GTGAAACAGCAGATGAATTCTACAGCACCATGGGGCGCCTTACCCAGGAGATGCTAGA                   GAATGATCTTCTGCAAAGCCATGAACTCATGCAGACTGTTTATTCCATGGCTCCGTTC                   CCTTTCCCACAATTGGCAGAGTTGAGGGAAAAATACACCTACAACATTACACCGTTCC                   CAGCCACAGTTAAACCCACCTCAGTTTCTGGACGACATAGTAAGGCCAGAGACAGTGA                   TGAAGAGAATGACCCAGACGATGAGGATGCTGTCGTTAATGCAGTGGGGTGTCTTGGA                   CCTTTTAGTGGGTTCCTGGCTCCTGAACTGCAGAAGTACCAAAAACAAATTAAAGAGC                   CAAATGAGGAGCAGAGTCTGAGATCTAATAACATTGCAGAGCTGAGTCCAGGAGCAAT                   CAATTCCTGTCGAAGTGAATACCATGCAGCTTTTAACAGTATGATGATGGAACGCATG                   ACCACAGATATCAATGCACTGAAGCGGCAGTACTCTCGAATTAAAAAGAAGCAACAGC                   AGCAGGTTCATCAGGTGTACATCAGGGCAGACAAAGGGCCAGTGACCAGCATTCTCCC                   GTCTCAGGTAAACAGTTCTCCAGTTATAAACCACCTTCTTTTAGGAAAGAAGATGAAA                   ATGACTAACAGAGCTGCCAAGAATGCTGTCATCCACATCCCTGGTCACACAGGAGGGA                   AAATATCTCCTGTCCCCTACGAAGACCTTAAGACGAAGCTCAACTCCCCGTGGCGAAC                   TCACATCCGAGTCCACAAAAAGAACATGCCAAGGACCAAGAGTCATCCGGGCTGTGGG                   GACACCGTAGGGCTGATAGATGAGCAGAACGAGGCCAGCAAGACCAATGGGCTGGGGG                   CAGCAGAGGCATTCCCCTCTGGTTGTACAGCGACAGCTGGGAGAGAAGGCAGCAGCCC                   TGAAGGCAGTACCAGGAGGACGATCGAGGGGCAGTCTCCGGAGCCGGTGTTCGGAGAT                   GCTGATGTGGATGTGTCTGCAGTTCAGGCGAAGTTGGGAGCCCTGGAACTGAACCAGA                   GGGATGCTGCAGCTGAAACTGAGCTCAGGGTGCACCCACCCTGCCAGCGGCACTGCCC                   AGAGCCGCCGAGTGCACCCGAAGAAAACAAAGCCACCAGCAAAGCTCCCCAAGGCAGC                   AACTCAAAAACCCCCATCTTTAGCCCTTTTCCCAGCGTCAAGCCCCTGCGGAAATCTG                   CTACTGCCAGGAACTTGGGATTATATGGCCCTACAGAAAGAACCCCAACTGTGCACTT                   TCCTCAAATGAGTAGGAGCTTCAGCAAACCCGGCGGTGGAAACAGTGGCACTAAAAAA                   CGA TGA   TGTCTCCCCGAAACTTTGTATCTGGACTCACCTTTTCACAGTAGTATAAGGG                       TTGCAGCTGAATGGCTCTAAAAGAGTTTTATTTGTCCAGTGAAAATGAATAGGTTCAG                       GGATGAGCAACAGCCCATAAAAAATGGGAACTGGAAGTTTTATAATAGGAGTTAGAAC                       AGGGCTGTTTTCCCAGCTACTTGCTAACTGACGAAGTGGATTCTTGTGGCAAAATAAA                       TATTGTGGTTTTATAGTGTGAAGTTTTCCCAATTTTTCATTGTGAGCTGTTTAAAAAA                       GACTATATCTAGATTGTTAACTCTCGTCCATCCTTCTGTTCTGGGGGCCTTCAGAGTC                       CCTGTGACAGCACCCCCAAACCTTCCAGTTCTCTGGGTGTTACTAATACTCAAGCATG                       CACATACCAGCTTGCTAGGACAGAAACTGTAAAAAGAAAGTAAGTTTCTTCGTTACAA                       AAAACTTCCTGATTTTCCTTTTCATGCTTTACGGAGGGGATTGTGTCGTGTGAGATTT                       CCCACAGTACCAGTTTCAAATTTTTTTTTATTCTTATGCTAAATCATAGGAGAAAAAT                       CTAGATGGCCTTTCTTTAACTGTCTATTTCTACCTGCAAAATGAAGAAAACCTTTCAT                       CTGTTGAAATTTCAATCGATAACCCAGCTGAAGATCTTATGCACAGGACACACTTGGC                       ATATGCTTTACGCAGTTGCTCCGGACAGCTTGCTCGCGCCACTGAGCTTTTCCTGAGG                       TTTGTGTTCGCCTCTCAAGGAGAGCTTTGATCCTCAGTGGTACGGATGACTTGATGGG                       CTCCATGCGGAGCCTGGCCTGCATCCCCCACCACACAGCTCACTCACCCACCAGCTCT                       AGACTGCAGACGCACAAGGCCTCTGCTCAGAAGCCAGAACACAGCACCTGTGACTCTG                       TTACTTGAATTTTGTGCTTTTTGATTGGAGTCCTTTGTTGAGTACTTTGTTAATTGAA                       CACTGCCTTTCTCTGGAGAAGGCCCCAGTGCTTTCTAGCTCCCTCTCACTCCTGCCCT                       TTCTAGCTCTCTCTCACCCAGCGGGTCAGGGATAGCACCTCTTGTCTCCACTATGCAG                       ATGGGAACTCTGAGCCACACAGAGGTGAAGTAGCACTTCAGTTACTCAAGGTCAGTAC                       TCTCGGTATTCCAAGTGACTTAGCCACATTTCCTTCAGTGCAATAGGTGGGTTTAATG                       CTCTTTGTACACAGATGTATTGGCTACATAGCGTGTAAAAACCAAGACTGGGAAGCCA                       TTCACTAAAATCCCTCCTGACTCAAAGGACCTGTCTCCAGATGGTACAGAGTCCCTTG                       ATGGCATTTTACAAAACCAGCTCTGACTTCCTTATCCTGAACAGGGAGTTTATTTTAA                       AAATGCTTCATGCACCTGTTATTTGGCTGAACAGAAGGCTCACTCCTCAATCCCCTTC                       TCCTCGCCATCATTAGAGGAATAGACTCAGCCTTCATGTTTGTCTCTGGAAGACGATT                       GGCGATACTTGCAGGAATATTGTTGATGCAGCCAATATTAATTTGAGCTAATGGATTG                       TTAATTCTGAAACGAAAACTGTAACTGTAGAGCAGGCTTTTACTATGAGAGGTACTAC                       TTTTTATAATAGAGAATGTGGTTGTGTGGGCTTTTTTTGAACAGAAAACACAACAATG                       ACCTATACCGTGAGAAAAGCCATTTTATCTTCTTCGTGGTATTTTTACCCCCAAAGGA                       ACTGAAGATGGAAAATATGACTAATAAGTTATTGCAGTTTTGGTCTTGAATTCTGTGC                       CATCTGAAGTTAGCATCCAGCTTCTTAAAAAGCAGCCACGCCTACAGCCTGTTTTTTG                       GGAAGGCTGTAGGTGGAGAGATGGGCTTATTTTGCATACCACCCTCAGGGCCCAGAGA                       CCCACTGCATTTTCCAAAGTTAAGCATGACACCATTTTCTTCCATCAGCTAAACTTTA                       CAGATAATAGTGTTTCCACCTCATATCCTTTTCTTTGCCCCTTCTCAAATGAGTCAGA                       ATAGTCATGTTCCCCTTGAGGGATGTCTGACTTGAATGGAGAATTGTTCTTTCCTCTC                       TTGAATCAGCTCACTAGCTCCCTGATGGTCTGGGTTCAAGGAAATGGTTAATGAGGTA                       GAGGCCACTTATACAAGTCCTTGGGATTGTACCATTGCTGTCCACAAACTTAGTATCA                       ACAACACATGCTGTGCCCTGTGAACACTCTCCTCTCACCTATTTCCAGGGTTGGTCTT                       CCTGAGAAGGGGATGGATGAGGTAACACACAGTTTGGGATACGTATCTGTTGAATGAA                       TGAATAAGTGAAAGGATAATAGTCCTCTGAGGTAAAAATGGCCTTGTCAGAATTTTGA                       AAATCCAACAGATTCCTATTAAAGCACTCTGTGTACCAATAACATGCATGCATTGTAC                       CAAGTAATCACAATGTGAATTGGTCAATTTATGAGCCTTGCCTACTTTAGAAAATAAA                       GAAACCTGCAGTAGCCTCTACCAC                                       ORF Start: ATG at 1   ORF Stop: TGA at 3136           SEQ ID NO:36   1045 aa MW at 114769.8 kD                     NOV18a,   MAPSETARKWERMLALTGVLPLRLAPLGAPSVPSQILGEARTSLFLLLVPERSYAPTG               CG105671-01   SLSLALLGTGELGRPRLRTADKLTGSLRRGGRCLKRQGGGVGTILSNVLKKRSCISRT               Protein Sequence   APRLLCTLEPGRGALGKVRVPPGAGHRVGTCRERLVWKGSQEARPCERCVGAESGTGL                   TLQVGGGRQWLQRQNRVLFSQESLQRECRGQLELEPVICECEWGAAGDPFHRLHNSVS                   APSPGIPPRDFKSLALARAPGHGGFWQGVAAEGVGCTLTGAWRSPVPWSGTGCVPGGF                   TVPGPRPPAPAPWGPAVEPQENRAAESLPACRLCHRREHGRTVCSGVDTKLKFTLEPS                   LGQNGFQQWYDALKAVARLSTGIPKEWRRKVWLTLADHYLHSIAIDWDKTMRFTFNER                   SNPDDDSMGIQIVKDLHRTGCSSYCGQEAEQDRVVLKRVLLAYARWNKTVGYCQGFNI                   LAALILEVMEGNEGDALKIMIYLIDKVLPESYFVNNLRALSVDMAVFRDLLRMKLPEL                   SQHLDTLQRTANKESGGGYEPPLTNVFTMQWFLTLFATCLPNQTVLKIWDSVFFEGSE                   IILRVSLAIWAKLGEQIECCETADEFYSTMGRLTQEMLENDLLQSHELMQTVYSMAPF                   PFPQLAELREKYTYNITPFPATVKPTSVSGRHSKARDSDEENDPDDEDAVVNAVGCLG                   PFSGFLAPELQKYQKQIKEPNEEQSLRSNNIAELSPGAINSCRSEYHAAFNSMMMERM                   TTDINALKRQYSRIKKKQQQQVHQVYIRADKGPVTSILPSQVNSSPVINHLLLGKKMK                   MTNRAAKNAVIHIPGHTGGKISPVPYEDLKTKLNSPWRTHIRVHKKNMPRTKSHPGCG                   DTVGLIDEQNEASKTNGLGAAEAFPSGCTATAGREGSSPEGSTRRTIEGQSPEPVFGD                   ADVDVSAVQAKLGALELNQRDAAAETELRVHPPCQRHCPEPPSAPEENKATSKAPQGS                   NSKTPIFSPFPSVKPLRKSATARNLGLYGPTERTPTVHFPQMSRSFSKPGGGNSGTKK                   R                  
 
     [0391] Further analysis of the NOV18a protein yielded the following properties shown in Table 18B.  
               TABLE 18B                       Protein Sequence Properties NOV18a                                        PSort   0.4865 probability located in mitochondrial matrix space;       analysis:   0.3000 probability located in microbody (peroxisome);           0.1977 probability located in mitochondrial inner membrane;           0.1977 probability located in mitochondrial           intermembrane space       SignalP   Cleavage site between residues 32 and 33       analysis:                  
 
     [0392] A search of the NOV18a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 18C.  
               TABLE 18C                          Geneseq Results for NOV18a                                         NOV18a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABG05609   Novel human diagnostic protein #   322 . . . 1045   715/727 (98%)   0.0           5600 -  Homo sapiens , 770 aa.   44 . . . 770   717/727 (98%)           [WO200175067-A2, 11-OCT-2001]       AAM39447   Human polypeptide SEQ ID NO   322 . . . 1045   715/727 (98%)   0.0           2592 -  Homo sapiens , 761 aa.   35 . . . 761   717/727 (98%)           [WO200153312-A1, 26-JUL-2001]       ABG05609   Novel human diagnostic protein #   322 . . . 1045   715/727 (98%)   0.0           5600 -  Homo sapiens , 770 aa.   44 . . . 770   717/727 (98%)           [WO200175067-A2, 11-OCT-2001]       AAM41234   Human polypeptide SEQ ID NO   322 . . . 1044   712/726 (98%)   0.0           6165 -  Homo sapiens , 798 aa.   44 . . . 769   714/726 (98%)           [WO200153312-A1, 26-JUL-2001]       AAM41233   Human polypeptide SEQ ID NO   322 . . . 1044   712/726 (98%)   0.0           6164 -  Homo sapiens , 798 aa.   44 . . . 769   714/726 (98%)           [WO200153312-A1, 26-JUL-2001]                  
 
     [0393] In a BLAST search of public sequence datbases, the NOV18a protein was found to have homology to the proteins shown in the BLASTP data in Table 18D.  
               TABLE 18D                          Public BLASTP Results for NOV18a                                         NOV18a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9Y219   KIAA0984 PROTEIN -  Homo      318 . . . 1045   728/728 (100%)   0.0             sapiens  (Human), 728 aa    1 . . . 728   728/728 (100%)           (fragment).       Q9D579   4930505D03RIK PROTEIN -    610 . . . 1045   377/440 (85%)    0.0             Mus musculus  (Mouse), 440 aa.    1 . . . 440   393/440 (88%)        Q9VH10   CG3996 PROTEIN -  Drosophila     354 . . . 819   183/496 (36%)    2e−81             melanogaster  (Fruit fly), 3111 aa.    84 . . . 520   259/496 (51%)        Q9NSH4   HYPOTHETICAL 54.4 KDA   367 . . . 647   92/288 (31%)   2e−26           PROTEIN -  Homo sapiens     162 . . . 422   143/288 (48%)            (Human), 468 aa.       Q9H6A2   CDNA: FLJ22452 FIS, CLONE   367 . . . 647   92/288 (31%)   2e−26           HRC09667 -  Homo sapiens     404 . . . 664   143/288 (48%)            (Human), 710 aa.                  
 
     [0394] PFam analysis predicts that the NOV18a protein contains the domains shown in the Table 18E.  
               TABLE 18E                          Domain Analysis of NOV18a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV18a Match Region   for the Matched Region   Value               TBC   367 . . . 600    73/342 (21%)   1.8e−26               156/342 (46%)                  
 
     Example 19  
     [0395] The NOV19 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 19A.  
               TABLE 19A                       NOV19 Sequence Analysis                                                SEQ ID NO:37   868 bp                     NOV19a,     A   ATG GCCACAGCCAGCTATCTGTATGGGCGGGGCTGCCCTGGAGATGCAGGGCAAGCG               CG105778-01   CCAGGAACCCCTCCGGGTAGCTACTACCTTGGACCCCCCAGTAGTGGAGGGCAGTATG               DNA Sequence   GCAGCGTGCTACCCCCTGGTGGTGGCTATGGGGGTCCTGCCCCTGGAGGGCCTTATGG                   ACCACCAGCTGGTAGAGGGCCCTATGGACACCTCAATCCTGGGATGTTCCCCTCTGGA                   ACTCCAGGAGGACCAAATGATGGTACAGCTCCAGGGGGCCCCTATGGTCAGCCACCTC                   CAAATTCCTACGGTGCCCAGCAGCCCAGGCCTCATGGACAGGGTGGCTCCCCTCCCAA                   TATGGATGAGGCCTACTCCTGGTTCCAGTCGGTGGACTCTGATCACAGTGGCTTTATC                   TCCATGAAGGAGGTGAAGCAGGCTCTGGTCAACTGCAACTGGTCCTTGTTCAATGATG                   AGACCTGCCTCATGATGATAAACATGTTTGACAAGACCAAATCAGGCCACATAAATGT                   CTACGGCTTCTCAGCCCTGTGGAAATTCATCCAGCAGTGGAAGCAGCTCTTCCAGCAG                   TATGACTGGGACAACTCAGGCTCCATTAGCTACACAGAGCTGCAGCAAGCTCTGTCCC                   AAATGGGCTACAACCTGAGCCCCCAGTTCACCCAGCTACTGGTCTCCAGCTACTGCCC                   ACGCTCTGTCAATCCTGCCAGACAGCTTGATTGCTTCATCCAGGTGTGCACCCAGCTG                   CAGATGCCGACAGAGGCCTTCCGGGAGAAGGACACAGCTGTACAAGGCAACATTCGGC                   TCAGCTTCAAGGACGTCGTCACCATGACAGCTCGGATGCTA TGA   CCCAACCCATCT                                       ORF Start: ATG at 2   ORF Stop: TGA at 854           SEQ ID NO:38   284 aa MW at 30581.0 kD                     NOV19a,   MATASYLYGRGCPGDAGQAPGTPPGSYYLGPPSSGGQYGSVLPPGGGYGGPAPGGPYG               CG105778-01   PPAGRGPYGHLNPGMFPSGTPGGPNDGTAPGGPYGQPPPNSYGAQQPRPHGQGGSPPN               Protein Sequence   MDEAYSWFQSVDSDHSGFISMKEVKQALVNCNWSLFNDETCLMMINMFDKTKSGHINV                   YGFSALWKFIQQWKQLFQQYDWDNSGSISYTELQQALSQMGYNLSPQFTQLLVSSYCP                   RSVNPARQLDCFIQVCTQLQMPTEAFREKDTAVQGNIRLSFKDVVTMTARML                  
 
     [0396] Further analysis of the NOV19a protein yielded the following properties shown in Table 19B.  
               TABLE 19B                       Protein Sequence Properties NOV19a                                        PSort   0.5472 probability located in microbody (peroxisome);       analysis:   0.4500 probability located in cytoplasm;           0.3024 probability located in lysosome (lumen);           0.1000 probability located in mitochondrial matrix space       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0397] A search of the NOV19a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 19C.  
               TABLE 19C                          Geneseq Results for NOV19a                                         NOV19a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAB87556   Human PRO3573 -  Homo sapiens ,   4 . . . 284   246/283 (86%)   e−147           284 aa. [WO200116318-A2, 08-MAR-2001]   2 . . . 284   257/283 (89%)       AAB92943   Human protein sequence SEQ ID   4 . . . 284   246/283 (86%)   e−147           NO: 11614 -  Homo sapiens , 284 aa.   2 . . . 284   257/283 (89%)           [EP1074617-A2, 07-FEB-2001]       AAU29141   Human PRO polypeptide sequence #   4 . . . 284   246/283 (86%)   e−147           118 -  Homo sapiens , 284 aa.   2 . . . 284   257/283 (89%)           [WO200168848-A2, 20-SEP-2001]       AAY44254   Human apoptosis linked gene-2   4 . . . 284   246/283 (86%)   e−147           like protein -  Homo sapiens , 284   2 . . . 284   257/283 (89%)           aa. [WO9961459-A1, 02-DEC-1999]       AAY82706   Human apoptosis related protein   4 . . . 284   246/283 (86%)   e−147           ABP32 SEQ ID NO: 2 -  Homo     2 . . . 284   257/283 (89%)             sapiens , 284 aa. [JP2000083672-A,           28-MAR-2000]                  
 
     [0398] In a BLAST search of public sequence datbases, the NOV19a protein was found to have homology to the proteins shown in the BLASTP data in Table 19D.  
               TABLE 19D                          Public BLASTP Results for NOV19a                                         NOV19a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9UBV8   PEFLIN (SIMILAR TO PEF   4 . . . 284   246/283 (86%)   e−146           PROTEIN WITH A LONG N-   2 . . . 284   257/283 (89%)           TERMINAL HYDROPHOBIC           DOMAIN) -  Homo sapiens             (Human), 284 aa.       Q8VCT5   RIKEN CDNA 2600002E23 GENE -   4 . . . 284   211/283 (74%)   e−119             Mus musculus  (Mouse), 275 aa.   2 . . . 275   225/283 (78%)       Q9D934   2600002E23RIK PROTEIN -  Mus     4 . . . 284   211/283 (74%)   e−119             musculus  (Mouse), 275 aa.   2 . . . 275   225/283 (78%)       Q9CYW8   2600002E23RIK PROTEIN -  Mus     4 . . . 257   186/255 (72%)   e−106             musculus  (Mouse), 268 aa.   2 . . . 247   199/255 (77%)       Q9V5M1   CG17765 PROTEIN (GH27120P) -   81 . . . 279     81/199 (40%)   1e−34              Drosophila melanogaster  (Fruit fly),   6 . . . 193   111/199 (55%)           199 aa.                  
 
     [0399] PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19E.  
               TABLE 19E                          Domain Analysis of NOV19a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV19a Match Region   for the Matched Region   Value               efhand   119 . . . 147   11/29 (38%)   0.0098               22/29 (76%)       efhand   186 . . . 214   10/29 (34%)   2.8e−05               25/29 (86%)                  
 
     Example 20  
     [0400] The NOV20 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 20A.  
               TABLE 20A                       NOV20 Sequence Analysis                                                SEQ ID NO:39   1491 bp                     NOV20a,     ATG CCAGATTATAGCAAAAGGATGTTGAGGGAGCAATATGAAAGCAAGCCTGAGAGTC               CG105796-01   CTGGAGAGAAGCAACCCCATGGGTATGAACTTGAGATGATTCACTTTCCTAAAAGCCT               DNA Sequence   CTTTGAGCTGAAAAAGGAAACGCGTTTTATGGCACTGCCACCTCTGGTCACCCACCCC                   GAGGTGTGGCAGACCTGGACAGACAGCATGACCGAGGGCCAGGCTGGTGAAGTCAAAC                   CTACCACTCAGGAAGGAGACCCAGCCCTTCTCCAGACAGAGTTCAAATTTTCCTCAGC                   TGAGAAATGGGGTGGGGGCAAATGGTCTAAGGTTCTGGGAACCTCTAAGTCAGATGAG                   GGAGAGGCCCTGAGGGTCAGCCGCACGCCTGAGAGGCAGGACAGACCCAAAGGTGGGC                   AACCTGAGCACATCAGGGTACTCAAGCAGCTGGCCTCTGGGGTAGCAGCCCTGGGTGT                   GAGAAGCAGGACTCAGAATCTAAGCCAACCCTCCACAGGAATCCCCTCTGGAGAGCCC                   GGGCACTCTGCAGGAGGGGCAGCAGGCAGCAGGTGCACCAGAAGCATGTTTCGCAAGG                   TGCCCAATAATGCCTCTGCTCTGATAGGCAGCGAGTTGGAACATGGATGCAGTAGGCA                   GGGTGGTGGCTGCTCCCCACAGCCAGGAGTCCAGCCCAGCACCCACCTGAGTCCACCT                   GAGTCCTGCTCAATTGGGTCATCCGTGCTCTGGGCCCTCTGGTCCCACCCACAGAGGG                   AGGGCTTTGGGGTGACCAGGCTCGCCTGGTCACGTGTCCTTCACTTTCCTCTGAGTCT                   CCCTCTTTCCAAGCCGCCTCCACTCTACTGGACACACTGTCCCTTAAGACACCAGAGT                   ACAGAAGCTCAAGTCCCTGCACCTCACCTTTACTCCCAGACATGGGAGGGACATGACA                   TAAAGACCCAAACGCCACTTGGCAAGAGTTCTGGGGAAGCTGCATGTAAGCTGGCTAT                   TGAATGTGGCTCTGAGCTGAGACCTCTCCTTGAAGCTCCAGACCAGGAGCCAGCTGCC                   AGCTGGACCCCGCCATTTGGTGCCTCAGAGAAACCTTGCACTCTTGTGGGACAGCTGC                   ACAAGGGCCCAGCATGTCTGTGTGTTTACCCAGGGAACTGCCGCATGGCTCATGCTGA                   GCAGAAGCTGATGGACGACCTTCTGAACAAAACCCGTTACAACAACCTGATCTGCCCA                   GCCACCAGCTCCTCACAGCTCATCTCCATCGAGACAGAGCTCTCCCTGGCGCAGTGCA                   TCAGTGTGCTTGCTCAACAGGTGACCTTACAGGCTCCCTACTTGTTGGGGGAAATAAG                   AACCAAACTGCGGGAACTGACGGGTACAGTGGCCCAGGAGGAAGCACAGCTGAAGGAT                   GCGAAGGGCAGTAGAGTTGTGTATGCTCCACCCCCTCTCTCCACAGTCAGATCGGAAA                   GAAGGGGGCTTTCAGCCAGGCTCGCCCAGACTGGGGTC TGA                                       ORF Start: ATG at 1   ORF Stop: TGA at 1489           SEQ ID NO:40   496 aa MW at 54061.8 kD                     NOV20a,   MPDYSKRMLREQYESKPESPGEKQPHGYELEMIHFPKSLFELKKETRFMALPPLVTHP               CG105796-01   EVWQTWTDSMTEGQAGEVKPTTQEGDPALLQTEFKFSSAEKWGGGKWSKVLGTSKSDE               Protein Sequence   GEALRVSRTPERQDRPKGGQPEHIRVLKQLASGVAALGVRSRTQNLSQPSTGIPSGEP                   GHSAGGAAGSRCTRSMFRKVPNNASALIGSELEHGCSRQGGGCSPQPGVQPSTHLSPP                   ESCSIGSSVLWALWSHPQREGFGVTRLAWSRVLHFPLSLPLSKPPPLYWTHCPLRHQS                   TEAQVPAPHLYSQTWEGHDIKTQTPLGKSSGEAACKLAIECGSELRPLLEAPDQEPAA                   SWTPPFGASEKPCTLVGQLHKGPACLCVYPGNCRMAHAEQKLMDDLLNKTRYNNLICP                   ATSSSQLISIETELSLAQCISVLAQQVTLQAPYLLGEIRTKLRELTGTVAQEEAQLKD                   AKGSRVVYAPPPLSTVRSERRGLSARLAQTGV                  
 
     [0401] Further analysis of the NOV20a protein yielded the following properties shown in Table 20B.  
               TABLE 20B                       Protein Sequence Properties NOV20a                                        PSort   0.4500 probability located in cytoplasm;       analysis:   0.3000 probability located in microbody (peroxisome);           0.1000 probability located in mitochondrial matrix           space; 0.1000 probability located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0402] A search of the NOV20a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 20C.  
               TABLE 20C                          Geneseq Results for NOV20a                                         NOV20a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAE10098   Human ion channel-73 (ion73)   379 . . . 432    49/54 (90%)    5e−21           protein -  Homo sapiens , 54 aa.   1 . . . 54   53/54 (97%)            [WO200168849-A2, 20-SEP-2001]       AAU83503   Novel human ion channel ion-103 -   379 . . . 428    45/50 (90%)    3e−17             Homo sapiens , 50 aa.   1 . . . 50   47/50 (94%)            [WO200202639-A2, 10-JAN-2002]       AAE10099   Human ion channel-74 (ion74)   379 . . . 428    45/50 (90%)    3e−17           protein -  Homo sapiens , 50 aa.   1 . . . 50   47/50 (94%)            [WO200168849-A2, 20-SEP-2001]       ABG05709   Novel human diagnostic protein #   95 . . . 133   39/39 (100%)   1e−15           5700 -  Homo sapiens , 464 aa.   94 . . . 132   39/39 (100%)           [WO200175067-A2, 11-OCT-2001]       ABG05709   Novel human diagnostic protein #   95 . . . 133   39/39 (100%)   1e−15           5700 -  Homo sapiens , 464 aa.   94 . . . 132   39/39 (100%)           [WO200175067-A2, 11-OCT-2001]                  
 
     [0403] In a BLAST search of public sequence datbases, the NOV20a protein was found to have homology to the proteins shown in the BLASTP data in Table 20D.  
               TABLE 20D                          Public BLASTP Results for NOV20a                                             Identities/                   NOV20a   Similarities       Protein       Residues/   for the       Accession       Match   Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               A30992   probable nicotinic acetylcholine   369 . . . 428   48/61 (78%)   2e−17           receptor precursor - rat, 517 aa.   31 . . . 91   54/61 (87%)       AAM11659   NICOTINIC ACETYLCHOLINE   378 . . . 428   42/51 (82%)   2e−15           RECEPTOR BETA4 SUBUNIT -   17 . . . 67   47/51 (91%)             Mus musculus  (Mouse), 495 aa.       P30926   Neuronal acetylcholine receptor   379 . . . 428   42/50 (84%)   4e−15           protein, beta-4 chain precursor -   19 . . . 68   47/50 (94%)             Homo sapiens  (Human), 498 aa.       AAL88712   NEURONAL NICOTINIC   379 . . . 428   41/50 (82%)   1e−14           ACETYLCHOLINE RECEPTOR   19 . . . 68   47/50 (94%)           BETA4 SUBUNIT -  Bos taurus             (Bovine), 496 aa.       B35721   nicotinic acetylcholine receptor   379 . . . 428   41/50 (82%)   2e−14           beta-4 chain precursor - rat, 495 aa.   18 . . . 67   46/50 (92%)                  
 
     [0404] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20E.  
               TABLE 20E                          Domain Analysis of NOV20a                                     Identities/                   Similarities       Pfam   NOV20a   for the   Expect       Domain   Match Region   Matched Region   Value               Neur_chan_LBD   387 . . . 428   14/47 (30%)   0.0064               33/47 (70%)                  
 
     Example 21  
     [0405] The NOV21 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 21A.  
               TABLE 21A                       NOV21 Sequence Analysis                                                SEQ ID NO:41   2879 bp                     NOV21a,     TTCGTCCCGGGCGGTGCGTTCCACTGCTCTGGGGCCGGCGCCGCGCCCAGTCCCGCTT                 CG106002-01     CGGGCCGCAAGCCCCACCGCTCCCCTCCCCGGGCAGGGGCGCCGCGCAGCCCGCTCCC                 DNA Sequence     GCCGCCACCTCCTCCCCTGCCGCCCTCCTAGCCGGCAGGAATTGCGCGACCACAGCGC                       CGCTCGCGTCGCCCGCATCAGCTCAGCCCGCTGCCGCTCGGCCCTCGGCACCGCTCCG                       GGTCCGGCCGCCGCGCGGCCAGGGCTCCCCCTGCCCAGCGCTCCCAGGCCCCGCCACG                       CGTCGCCGCGCCCAGCTCCAGTCTCCCCTCCCCGGGGTCTCGCCAGCCCCTTCCTGCA                       GCCGCCGCCTCCGAAGGAGCGGGTCCGCCGCGGGTAACC ATGCCTAGCAAAACCAAGT                   ACAACCTTGTGGACGATGGGCACGACCTGCGGATCCCCTTGCACAACGAGGACGCCTT                   CCAGCACGGCATCTGCTTTGAGGCCAAGTACGTAGGAAGCCTGGACGTGCCAAGGCCC                   AACAGCAGGGTGGAGATCGTGGCTGCCATGCGCCGGATACGGTATGAGTTTAAAGCCA                   AGAACATCAAGAAGAAGAAAGTGAGCATTATGGTTTCAGTGGATGGAGTGAAAGTGAT                   TCTGAAGAAGAAGAAAAAGCTTCTTTTATTGCAGAAAAAGGAATGGACGTGGGATGAG                   AGCAAGATGCTGGTGATGCAGGACCCCATCTACAGGATCTTCTATGTCTCTCATGATT                   CCCAAGACTTGAAGATCTTCAGCTATATCGCTCGAGATGGTGCCAGCAATATCTTCAG                   GTGTAACGTCTTTAAATCCAAGAAGAAGAGCCAAGCTATGAGAATCGTTCGGACGGTG                   GGGCAGGCCTTTGAGGTCTGCCACAAGCTGAGCCTGCAGCACACGCAGCAGAATGCAG                   ATGGCCAGGAAGATGGAGAGAGTGAGAGGAACAGCAACAGCTCAGGAGACCCAGGCCG                   CCAGCTCACTGGAGCCGAGAGGGCCTCCACGGCCACTGCAGAGGAGACTGACATCGAT                   GCGGTGGAGGTCCCACTTCCAGGGAATGATGTCCTGGAATTCAGCCGAGGTGTGACTG                   ATCTAGATGCTGTAGGGAAGGAAGGAGGCTCTCACACAGGCTCCAAGGTTTCGCACCC                   CCAGGAGCCCATGCTGACAGCCTCACCCAGGATGCTGCTCCCTTCTTCTTCCTCGAAG                   CCTCCAGGCCTGGGCACAGAGACACCGCTGTCCACTCACCACCAGATGCAGCTCCTCC                   AGCAGCTCCTCCAGCAGCAGCAGCAGCAGACACAAGTGGCTGTGGCCCAGGTACACTT                   GCTGAAGGACCAGTTGGCTGCTGAGGCTGCGGCGCGGCTGGAGGCCCAGGCTCGCGTG                   CATCAGCTTTTGCTGCAGAACAAGGACATGCTCCAGCACATCTCCCTGCTGGTCAAGC                   AGGTGCAAGAGCTGGAACTGAAGCTGTCAGGACAGAACGCCATGGGCTCCCAGGACAG                   CTTGCTGGAGATCACCTTCCGCTCCGGAGCCCTGCCCGTGCTCTGTGACCCCACGACC                   CCTAAGCCAGAGGACCTGCATTCGCCGCCGCTGGGCGCGGGCTTGGCTGACTTTGCCC                   ACCCTGCGGGCAGCCCCTTAGGTAGGCGCGACTGCTTGGTGAAGCTGGAGTGCTTTCG                   CTTTCTTCCGCCCGAGGACACCCCGCCCCCAGCGCAGGGCGAGGCGCTCCTGGGCGGT                   CTGGAGCTCATCAAGTTCCGAGAGTCAGGCATCGCCTCGGAGTACGAGTCCAACACGG                   ACGAGAGCGAGGAGCGCGACTCGTGGTCCCAGGAGGAGCTGCCGCGCCTGCTGAATGT                   CCTGCAGAGGCAGGAACTGGGCGACGGCCTGGATGATGAGATCGCCGTGTAG GTGCCG                       AGGGCGAGGAGATGGAGGCGGCGGCGTGGCTGGAGGGGCCGTGTCTGGCTGCTGCCCG                       GGTAGGGGATGCCCAGTGAATGTGCACTGCCGAGGAGAATGCCAGCCAGGGCCCGGGA                       GAGTGTGAGGTTTCAGGAAAGTATTGAGATTCTGCTTTGGAGGGTAAAGTGGGGAAGA                       AATCGGATTCCCAGAGGTGAATCAGCTCCTCTCCTACTTGTGACTAGAGGGTGGTGGA                       GGTAAGGCCTTCCAGAGCCCATGGCTTCAGGAGAGGGTCTCTCTCCAGGACTGCCAGG                       CTGCTGGAGGACCTGCCCCTACCTGCTGCATCGTCAGGCTCCCACGCTTTGTCCGTGA                       TGCCCCCCTACCCCCTCACTCTCCCCGTCTCCATGGTCCCGACCAGGAAGGGAAGCCA                       TCGGTACCTTCTCAGGTACTTTGTTTCTGGATATCACGATGCTGCGAGTTGCCTAACC                       CTCCCCCTACCTTTATGAGAGGAATTCCTTCTCCAGGCCCTTGCTGAGATTGTAGAGA                       TTGAGTGCTCTGGACCGCAAAAGCCAGGCTAGTCCTTGTAGGGTGAGCATGGAATTGG                       AATGTGTCACAGTGGATAAGCTTTTAGAGGAACTGAATCCAAACATTTTCTCCAGCCG                       GACATTGAATGTTGCTACAAAGGGAGCCTTGAAGCTTTAACATGGTTCAGGCCCTTGG                       TGTGAGAGCCCAGGGGGAGGACAGCTTGTCTGCTGCTCCAAATCACTTAGATCTGATT                       CCTGTTTTGAAAGTCCTGCCCTGCCTTCCTCCTGCCTGTAGCCCAGCCCATCTAAATG                       GAAGCTGGGAATTGCCCCTCACCTCCCCTGTGTCCTGTCCAGCTGAAGCTTTTGCAGC                       ACTTTACCTCTCTGAAAGCCCCAGAGGACCAGAGCCCCCAGCCTTACCTCTCAACCTG                       TCCCCTCCACTGGGCAGTGGTGGTCAGTTTTTACTGC                                       ORF Start: ATG at 388   ORF Stop: TAG at 1906           SEQ ID NO:42   506 aa MW at 56149.2 kD                     NOV21a,   MPSKTKYNLVDDGHDLRIPLHNEDAFQHGICFEAKYVGSLDVPRPNSRVEIVAAMRRI               CG106002-01   RYEFKAKNIKKKKVSIMVSVDGVKVILKKKKKLLLLQKKEWTWDESKMLVMQDPIYRI               Protein Sequence   FYVSHDSQDLKIFSYIARDGASNIFRCNVFKSKKKSQAMRIVRTVGQAFEVCHKLSLQ                   HTQQNADGQEDGESERNSNSSGDPGRQLTGAERASTATAEETDIDAVEVPLPGNDVLE                   FSRGVTDLDAVGKEGGSHTGSKVSHPQEPMLTASPRMLLPSSSSKPPGLGTETPLSTH                   HQMQLLQQLLQQQQQQTQVAVAQVHLLKDQLAAEAAARLEAQARVHQLLLQNKDMLQH                   ISLLVKQVQELELKLSGQNAMGSQDSLLEITFRSGALPVLCDPTTPKPEDLHSPPLGA                   GLADFAHPAGSPLGRRDCLVKLECFRFLPPEDTPPPAQGEALLGGLELIKFRESGIAS                   EYESNTDESEERDSWSQEELPRLLNVLQRQELGDGLDDEIAV                  
 
     [0406] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.  
               TABLE 21B                       Protein Sequence Properties NOV21a                                        PSort   0.9700 probability located in nucleus;       analysis:   0.3000 probability located in microbody (peroxisome);           0.1000 probability located in mitochondrial matrix space;           0.1000 probability located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0407] A search of the NOV21a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 21C.  
               TABLE 21C                          Geneseq Results for NOV21a                                         NOV21a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABB04838   LDL receptor binding protein   1 . . . 506   476/508 (93%)   0.0           CAPON SEQ ID NO: 61 -   1 . . . 503   483/508 (94%)           Synthetic, 503 aa. [WO200184159-           A2, 08-NOV-2001]       AAY28473   Rat Capon protein - Rattus sp, 503   1 . . . 506   476/508 (93%)   0.0           aa. [WO9937768-A1, 29-JUL-1999]   1 . . . 503   483/508 (94%)       ABB04846   LDL receptor binding protein   1 . . . 506   432/508 (85%)   0.0           CAPON SEQ ID NO: 69 -   1 . . . 503   444/508 (87%)           Synthetic, 503 aa. [WO200184159-           A2, 08-NOV-2001]       ABB04847   LDL receptor binding protein   1 . . . 506   429/508 (84%)   0.0           CAPON SEQ ID NO: 70 -   1 . . . 503   440/508 (86%)           Synthetic, 503 aa. [WO200184159-           A2, 08-NOV-2001]       ABB04845   LDL receptor binding protein   1 . . . 506   431/508 (84%)   0.0           CAPON SEQ ID NO: 68 -   1 . . . 503   440/508 (85%)           Synthetic, 503 aa. [WO200184159-           A2, 08-NOV-2001]                  
 
     [0408] In a BLAST search of public sequence datbases, the NOV21a protein was found to have homology to the proteins shown in the BLASTP data in Table 21D.  
               TABLE 21D                          Public BLASTP Results for NOV21a                                         NOV21a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               O75052   KIAA0464 PROTEIN -  Homo     1 . . . 506   506/506 (100%)   0.0             sapiens  (Human), 586 aa   81 . . . 586    506/506 (100%)           (fragment).       O54960   CARBOXYL-TERMINAL PDZ   1 . . . 506   476/508 (93%)    0.0           LIGAND OF NEURONAL   1 . . . 503   483/508 (94%)            NITRIC OXIDE SYNTHASE -             Rattus norvegicus  (Rat), 503 aa.       Q9D3A8   6330408P19RIK PROTEIN -  Mus     1 . . . 316   295/317 (93%)     e−165             musculus  (Mouse), 325 aa.   1 . . . 312   300/317 (94%)        O43564   CARBOXYL-TERMINAL PDZ   354 . . . 506    153/153 (100%)   2e−84           LIGAND OF NEURONAL   1 . . . 153   153/153 (100%)           NITRIC OXIDE SYNTHASE -             Homo sapiens  (Human), 153 aa           (fragment).       AAL68331   RE71517P -  Drosophila     1 . . . 382   166/384 (43%)    1e−72             melanogaster  (Fruit fly), 698 aa.   1 . . . 358   230/384 (59%)                   
 
     [0409] PFam analysis predicts that the NOV21a protein contains the domains shown in the Table 21E.  
               TABLE 21E                          Domain Analysis of NOV21a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV21a Match Region   for the Matched Region   Value               PID   32 . . . 175    49/167 (29%)   6.2e−44               127/167 (76%)                  
 
     Example 22  
     [0410] The NOV22 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 22A.  
               TABLE 22A                       NOV22 Sequence Analysis                                                SEQ ID NO:43   3252 bp                     NOV22a,     GGCTGCCTGACCTCCTTGGGTGCTTGCTATTAATTAACAGACTTTGTGGGGAAAAAAA                 CG106868-01     GGAGCTTGCCTTCTGAGCTTTGTACCAAAGACCTGGGAAAAATTTCAAATTATAACCT                 DNA Sequence     ATTTCCTGCACCATTGCTGACGCCTGGTGATCC ATGTCAGAAGTACTTCCAGCTGACT                   CAGGTGTTGACACCTTGGCAGTGTTTATGGCCAGCAGCGGAACTACAGACGTCACAAA                   TCGGAACAGCCCAGCCACACCACCAAACACCCTTAACCTCCGATCCTCCCACAATGAA                   CTGTTGAACGCTGAAATAAAACACACAGAAACCAAGAACAGCACACCTCCCAAATGCA                   GGAAAAAATATGCACTAACTAACATCCAGGCGGCCATGGGCCTCTCGGATCCAGCTGC                   ACAGCCCCTGCTGGGAAATGGCTCTGCCAACATCAAGCTGGTGAAAAATGGGGAGAAC                   CAGCTCCGTAAGGCTGCAGAGCAAGGGCAGCAGGACCCCAACAAAAACCTGAGCCCCA                   CTGCAGTCATCAACATAACTTCTGAGAAGTTAGAGGGTAAAGAGCCCCACCCACAGGA                   TTCCTCGAGCTGTGAGATTTTACCCTCCCAGCCCAGGAGAACTAAGAGCTTCCTAAAT                   TACTATGCAGATCTGGAAACCTCAGCCAGAGAACTAGAGCAGAACCGAGGCAATCACC                   ATGGGACTGCGGAAGAGAAATCCCAGCCAGTCCAGGGCCAGGCCTCCACCATCATTGG                   GAATGGCGATTTGCTGCTGCAGAAACCAAACAGACCCCAGTCCAGCCCTGAAGACGGC                   CAAGTAGCCACAGTGTCATCCAGCCCAGAAACCAAGAAGGATCATCCGAAAACAGGGG                   CCAAAACCGACTGTGCACTGCACCGGATCCAGAACCTGGCACCGAGCGATGAGGAGTC                   CAGCTGGACAACGTTGTCCCAAGACAGTGCCTCACCCAGCTCCCCGGATGAAACAGCA                   GATATATGGAGTGATCACTCATTTCAGACTGATCCAGATTTGCCGCCTGGCTGGAAAA                   GAGTCAGTGACATTGCCGGGACCTATTATTGGCACATCCCAACAGGAACGACTCAGTG                   TCTGTAACGCCATCTCCCACCCCAGAGAACGAGAAACAGCCATGGAGTGATTTTGCTG                   TTCTGAATGGGGGAAAGATTAATAGTGACATTTGGAAGGATTTGCATGCAGCCACTGT                   TAACCCGGACCCCAGTTTAAAAGAGTTTGAAGGAGCAACCCTACGCTATGCATCTTTG                   AAACTCAGAAATGCCCCACACCCTGATGATGATGATTCTTGTAGTATCAACAGTGACC                   CAGAAGCCAAGTGTTTTGCTGTGCGTTCTCTGGGATGGGTAGAGATGGCAGAAGAGGA                   CCTCGCCCCCGGTAAAAGTAGTGTTGCGGTCAACAACTGCATCAGGCAACTTTCCTAC                   TGCAAAAATGACATCCGAGACACAGTCGGGATTTGGGGAGAGGGGAAAGACATGTACC                   TGATCCTGGAGAATGACATGCTCAGCCTGGTGGACCCCATGGACCGCAGCGTGCTGCA                   CTCGCAGCCCATCGTCAGCATCCGCGTGTGGGGCGTGGGCCGCGACAATGGCCGGGAT                   TTTGCTTATGTAGCAAGAGATAAAGATACAAGAATTTTGAAATGTCATGTATTTCGAT                   GTGACACACCAGCAAAAGCCATTGCCACAAGTCTCCACGAGATCTGCTCCAAGATTAT                   GGCTGAACGGAAGAATGCCAAAGCGCTGGCCTGCAGCTCCTTACAGGAAAGGGCCAAT                   GTGAACCTCGATGTCCCTTTGCAAGTAGATTTTCCAACACCAAAGACTGAGCTGGTCC                   AGAAGTTCCACGTGCAGTACTTGGGCATGTTACCTGTAGACAAACCAGTCGGAATGGA                   TATTTTGAACAGTGCCATAGAAAATCTTATGACCTCATCCAACAAGGAGGACTGGCTG                   TCAGTGAACATGAACGTGGCTGATGCCACTGTGACTGTCATCAGTGAAAAGAATGAAG                   AGGAAGTCTTAGTGGAATGTCGTGTGCGATTCCTGTCCTTCATGGGTGTTGGGAAGGA                   CGTCCACACATTTGCCTTCATCATGGACACGGGGAACCAGCGCTTTGAGTGCCACGTT                   TTCTGGTGCGAGCCTAATGCTGGTAACGTGTCTGAAGCGGTGCAGGCCGCCTGCATGT                   TACGATATCAGAAGTGCTTGGTAGCCAGGCCGCCTTCTCAGAAAGTTCGACCACCTCC                   ACCGCCAGCAGATTCAGCGACCAGAAGAGTCACGACCAATGTAAAACGAGGGGTCTTA                   TCCCTCATTGACACTTTGAAACAGAAACGCCCTGTCACCGAAATGCCATAG CTGCACA                       TGCAAAAGGACTCGGCTATTTACCTGAAGATTGACTAGCTACACTAAAGAAAATGAAC                       TCCGCCATCCGACCTTCCATCCAGTTGCTGATGCTTTGTCTTCAGAGAATTTACCCTT                       AACCAAGCAGTGTTAGACAAGCATGTTCTCTCGTCTTGCCACCATCATGTGATATGAA                       AAGAAGCATGAATAATTTTTTTTGCTGTAAGTTACATCATGCGCAGTGGAAGGTCTTT                       TTCTTATTGTAAATATTGTGAACATTACTTAACTTCACACACACACAGAGAAGAGTGT                       GGCCCCACCCCTCCTAGTGAACTAACGCTGCGTCCTTGGAATGAATGATGCGTGAGTT                       AGTTTCACTGTCTTCTTGGCTGGACCTGTCACAAGCAACCTTTAAGTCCTACAGCACT                       TTGCCCTGTTTTCAACATTGGAGTAGGCACTGCATAGCAGATACCATTGAATTGCTGT                       AAAAATAGGATGGCGAGTTTGTGTTTTAATTTTTCATAAAATTGAACCTGTTGGTTGA                       CAAAATTGGCTGTTGGCATCAGTATAGAAACCAACTGGCAGCTTTCCCTGACAAGCTC                       TTTGACACATGGACACCATTTCATGTCTACAGCTGTTTGTGGGATGTTGGAAAAAAAT                       GAAACTTCAAAATTGATGAAAAACTAAATTCGAGGAATTAAAATCGAACAAAACATAG                       CCTTTCTTTTCCGATGGTTTTCAAACTGATTATTTTTAAAAGAGATTAATAAAATCAT                       AATGCATTTTGGGTGGGACATATTTCAAGCTTCTGCCTTATATTGTACCTGCCCGGGC                       GGAA                                       ORF Start: ATG at 150   ORF Stop: TAG at 2427           SEQ ID NO:44   759 aa MW at 83415.8 kD                     NOV22a,   MSEVLPADSGVDTLAVFMASSGTTDVTNRNSPATPPNTLNLRSSHNELLNAEIKHTET               CG106868-01   KNSTPPKCRKKYALTNIQAAMGLSDPAAQPLLGNGSANIKLVKNGENQLRKAAEQGQQ               Protein Sequence   DPNKNLSPTAVINITSEKLEGKEPHPQDSSSCEILPSQPRRTKSFLNYYADLETSARE                   LEQNRGNHHGTAEEKSQPVQGQASTIIGNGDLLLQKPNRPQSSPEDGQVATVSSSPET                   KKDHPKTGAKTDCALHRIQNLAPSDEESSWTTLSQDSASPSSPDETADIWSDHSFQTD                   PDLPPGWKRVSDIAGTYYWHIPTGTTQWERPVSIPADLQGSRKGSLSSVTPSPTPENE                   KQPWSDFAVLNGGKINSDIWKDLHAATVNPDPSLKEFEGATLRYASLKLRNAPHPDDD                   DSCSINSDPEAKCFAVRSLGWVEMAEEDLAPGKSSVAVNNCIRQLSYCKNDIRDTVGI                   WGEGKDMYLILENDMLSLVDPMDRSVLHSQPIVSIRVWGVGRDNGRDFAYVARDKDTR                   ILKCHVFRCDTPAKAIATSLHEICSKIMAERKNAKALACSSLQERANVNLDVPLQVDF                   PTPKTELVQKFHVQYLGMLPVDKPVGMDILNSAIENLMTSSNKEDWLSVNMNVADATV                   TVISEKNEEEVLVECRVRFLSFMGVGKDVHTFAFIMDTGNQRFECHVFWCEPNAGNVS                   EAVQAACMLRYQKCLVARPPSQKVRPPPPPADSATRRVTTNVKRGVLSLIDTLKQKRP                   VTEMP                  
 
     [0411] Further analysis of the NOV22a protein yielded the following properties shown in Table 22B.  
               TABLE 22B                       Protein Sequence Properties NOV22a                                        PSort   0.3000 probability located in nucleus;       analysis:   0.1000 probability located in mitochondrial matrix space;           0.1000 probability located in lysosome (lumen);           0.0000 probability located in endoplasmic reticulum           (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0412] A search of the NOV22a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 22C.  
               TABLE 22C                          Geneseq Results for NOV22a                                         NOV22a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAY13459   Amino acid sequence of human    44 . . . 759   695/716 (97%)   0.0           Fe65-like protein -  Homo sapiens ,    16 . . . 730   699/716 (97%)           730 aa. [WO9921995-A1, 06-MAY-1999]       AAY13458   Amino acid sequence of human    20 . . . 753   345/752 (45%)   e−168           Fe65 -  Homo sapiens , 710 aa.    5 . . . 704   465/752 (60%)           [WO9921995-A1, 06-MAY-1999]       AAY13454   Amino acid sequence of rat Fe65 -   250 . . . 759   282/515 (54%)   e−156           Rattus sp, 499 aa. [WO9921995-    1 . . . 499   367/515 (70%)           A1, 06-MAY-1999]       AAW24798   Carboxy-terminal region of   250 . . . 759   282/515 (54%)   e−156           amyloid precursor protein -  Homo      1 . . . 499   367/515 (70%)             sapiens , 499 aa. [FR2740454-A1,           30-APR-1997]       AAW49835   Amino acid sequence of the rat   346 . . . 753   233/412 (56%)   e−126           protein FE65 - Rattus sp, 425 aa.    2 . . . 410   299/412 (72%)           [WO9821327-A1, 22-MAY-1998]                  
 
     [0413] In a BLAST search of public sequence datbases, the NOV22a protein was found to have homology to the proteins shown in the BLASTP data in Table 22D.  
               TABLE 22D                          Public BLASTP Results for NOV22a                                         NOV22a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q92870   Amyloid beta A4 precursor protein-   44 . . . 759   695/716 (97%)   0.0           binding family B member 2 (Fe65-   16 . . . 730   699/716 (97%)           like protein) -  Homo sapiens             (Human), 730 aa (fragment).       Q9QXJ1   Amyloid beta A4 precursor protein-   20 . . . 759   350/757 (46%)   e−172           binding family B member 1 (Fe65    5 . . . 708   474/757 (62%)           protein) -  Mus musculus  (Mouse),           708 aa.       Q99MK3   FE65 -  Rattus norvegicus  (Rat), 711   20 . . . 759   347/759 (45%)   e−170           aa.    5 . . . 711   467/759 (60%)       Q96A93   SIMILAR TO AMYLOID BETA   20 . . . 753   345/750 (46%)   e−169           (A4) PRECURSOR PROTEIN-    5 . . . 702   465/750 (62%)           BINDING, FAMILY B, MEMBER           1 (FE65) -  Homo sapiens  (Human),           708 aa.       O00213   Amyloid beta A4 precursor protein-   20 . . . 753   345/752 (45%)   e−168           binding family B member 1 (Fe65    5 . . . 704   465/752 (60%)           protein) -  Homo sapiens  (Human),           710 aa.                  
 
     [0414] PFam analysis predicts that the NOV22a protein contains the domains shown in the Table 22E.  
               TABLE 22E                          Domain Analysis of NOV22a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV22a Match Region   for the Matched Region   Value               WW   293 . . . 321    15/30 (50%)     3e−09                24/30 (80%)       PID   420 . . . 556    47/161 (29%)   1.1e−50               128/161 (80%)       PID   591 . . . 713    46/161 (29%)   1.8e−46               112/161 (70%)                  
 
     Example 23  
     [0415] The NOV23 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 23A.  
               TABLE 23A                       NOV23 Sequence Analysis                                                SEQ ID NO:45   1322 bp                     NOV23a,     CGCGCCTGAAGAGCCGCAGAGAGAGCTGGGAGCTAAGGGGTGGCGGCGACCGGAAGCG                 CG106988-01     CAGTGCACACCCCC ATGGCCCGGGCTTTGGTCCAGCTCTGGGCCATATGCATGCTGCG               DNA Sequence   AGTGGCGCTGGCTACCGTCTATTTCCAAGAGGAATTTCTAGACGGAGAGCATTGGAGA                   AACCGATGGTTGCAGTCCACCAATGACTCCCGATTTGGGCATTTTAGACTTTCGTCGG                   GCAAGTTTTATGGTCATAAAGAGAAAGATAAAGGTCTGCAAACCACTCAGAATGGCCG                   ATTCTATGCCATCTCTGCACGCTTCAAACCGTTCAGCAATAAAGGGAAAACTCTGGTT                   ATTCAGTACACAGTAAAACATGAGCAGAAGATGGACTGTGGAGGGGGCTACATTAAGG                   TCTTTCCTGCAGACATTGACCAGAAGAACCTGAATGGAAAATCGCAGTACTATATTAT                   GTTTGGACCCGATATTTGTGGATTTGATATCAAGAAAGTTCATGTTATTTTACATTTC                   AAGAATAAGTATCACGAAAACAAGAAACTGATCAGGTGTAAGGTTGATGGCTTCACAC                   ACCTGTACACTCTAATTTTAAGACCAGATCTTTCTTATGATGTGAAAATTGATGGTCA                   GTCAATTGAATCCGGCAGCATAGAGTACGACTGGAACTTAACATCACTCAAGAAGGAA                   ACGTCCCCGGCAGAATCGAAGGATTGGGAACAGACTAAAGACAACAAAGCCCAGGACT                   GGGAGAAGCATTTTCTGGACGCCAGCACCAGCAAGCAGAGCGACTGGAACGGTGACCT                   GGATGGGGACTGGCCAGCGCCGATGCTCCAGAAGCCCCCGTACCAGGATGGCCTGAAA                   CCAGAAGGTATTCATAAAGACGTCTGGCTCCACCGTAAGATGAAGAATACCGACTATT                   TGACGCAGTATGACCTCTCAGAATTTGAGAACATTGGTGCCATTGGCCTGGAGCTTTG                   GCAGGTCATTTGGCATCTGCAGGTGAGATCTGGAACCATTTTTGATAACTTTCTGATC                   ACAGATGATGAAGAGTACGCAGATAATTTTGGCAAGGCCACCTGGGGCGAAACCAAGG                   GTCCAGAAAGGGAGATGGATGCCATACAGGCCAAGGAGGAAATGAAGAAGGCCCGCGA                   GGAAGAGGAGGAAGAGCTGCTGTCGGGAAAAATTAACAGGCACGAACATTACTTCAAT                   CAATTTCACAGAAGGAATGAACTTTAG TGATCCCCATTGGATATAAGGATGACTGGTA                       AAATCTCATTGCTACTTTAATCTATGTTTCAAACTCAAATGTCAAA                                       ORF Start: ATG at 73   ORF Stop: TAG at 1243           SEQ ID NO:46   390 aa MW at 45772.2 kD                     NOV23a,   MARALVQLWAICMLRVALATVYFQEEFLDGEHWRNRWLQSTNDSRFGHFRLSSGKFYG               CG106988-01   HKEKDKGLQTTQNGRFYAISARFKPFSNKGKTLVIQYTVKHEQKMDCGGGYIKVFPAD               Protein Sequence   IDQKNLNGKSQYYIMFGPDICGFDIKKVHVILHFKNKYHENKKLIRCKVDGFTHLYTL                   ILRPDLSYDVKIDGQSIESGSIEYDWNLTSLKKETSPAESKDWEQTKDNKAQDWEKHF                   LDASTSKQSDWNGDLDGDWPAPMLQKPPYQDGLKPEGIHKDVWLHRKMKNTDYLTQYD                   LSEFENIGAIGLELWQVIWHLQVRSGTIFDNFLITDDEEYADNFGKATWGETKGPERE                   MDAIQAKEEMKKAREEEEEELLSGKINRHEHYFNQFHRRNEL                  
 
     [0416] Further analysis of the NOV23a protein yielded the following properties shown in Table 23B.  
               TABLE 23B                       Protein Sequence Properties NOV23a                                        PSort   0.6377 probability located in outside;       analysis:   0.2484 probability located in microbody (peroxisome);           0.1900 probability located in lysosome (lumen);           0.1000 probability located in endoplasmic           reticulum (membrane)       SignalP   Cleavage site between residues 20 and 21       analysis:                  
 
     [0417] A search of the NOV23a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 23C.  
               TABLE 23C                          Geneseq Results for NOV23a                                         NOV23a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               AAB32385   Human secreted protein sequence    1 . . . 390   384/390 (98%)   0.0           encoded by gene 15 SEQ ID NO: 71 -    1 . . . 384   384/390 (98%)             Homo sapiens , 385 aa.           [WO200047602-A1, 17-AUG-2000]       AAY92349   Human MBP-calreticulin -  Homo     14 . . . 368   192/376 (51%)   e−108             sapiens , 417 aa. [WO200020577-   14 . . . 383   254/376 (67%)           A1, 13-APR-2000]       AAP92276   60 kD Ro (Ro/SSA) antigen -   14 . . . 368   192/376 (51%)   e−108           Synthetic, 417 aa. [WO8909273-A,   14 . . . 383   254/376 (67%)           05-OCT-1989]       AAY00927   Calreticulin -  Homo sapiens , 417   14 . . . 368   192/376 (51%)   e−107           aa. [WO9907406-A1, 18-FEB-1999]   14 . . . 383   253/376 (67%)       AAY92350   Recombinant human MBP-   21 . . . 368   189/369 (51%)   e−107           calreticulin -  Homo sapiens , 400 aa.    4 . . . 366   251/369 (67%)           [WO200020577-A1, 13-APR-2000]                  
 
     [0418] In a BLAST search of public sequence datbases, the NOV23a protein was found to have homology to the proteins shown in the BLASTP data in Table 23D.  
               TABLE 23D                          Public BLASTP Results for NOV23a                                         NOV23a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96LN3   CDNA FLJ25355 FIS, CLONE    1 . . . 390   384/390 (98%)   0.0           TST01593 -  Homo sapiens      1 . . . 384   384/390 (98%)           (Human), 384 aa.       Q96L12   SIMILAR TO RIKEN CDNA    1 . . . 390   383/390 (98%)   0.0           1700031L01 GENE -  Homo sapiens      1 . . . 384   383/390 (98%)           (Human), 384 aa.       Q9D9Q6   1700031L01RIK PROTEIN -  Mus      2 . . . 390   319/390 (81%)   0.0             musculus  (Mouse), 380 aa.    4 . . . 380   350/390 (88%)       P18418   Calreticulin precursor (CRP55)   14 . . . 378   192/386 (49%)   e−108           (Calregulin) (HACBP) (ERP60)   14 . . . 393   260/386 (66%)           (CALBP) (Calcium-binding protein           3) (CABP3) -  Rattus norvegicus             (Rat), 416 aa.       P27797   Calreticulin precursor (CRP55)   14 . . . 368   192/376 (51%)   e−107           (Calregulin) (HACBP) (ERp60) -   14 . . . 383   254/376 (67%)             Homo sapiens  (Human), 417 aa.                  
 
     [0419] PFam analysis predicts that the NOV23a protein contains the domains shown in the Table 23E.  
               TABLE 23E                          Domain Analysis of NOV23a                                 NOV23a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               calreticulin    21 . . . 200    99/207 (48%)   9.1e−93               148/207 (71%)       calreticulin   275 . . . 324    24/51 (47%)     4e−11                35/51 (69%)                  
 
     Example 24  
     [0420] The NOV24 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 24A.  
               TABLE 24A                       NOV24 Sequence Analysis                                                SEQ ID NO:47   543 bp                     NOV24a,     ATGGCTGCCCGGACGCGGAGCGAGAGGGTGAGAGAGTCCGAGACACTATCCCGTTCCC                 CG107363-01     TTCCGTCGCGCAGACCCTGCCGGAGCCGCTGCCGCT ATGGATGATCGAGAGGATCTGG               DNA Sequence   TGTACCAGGCGAAGCTGGCCGAGCAGGCTGAGCGATACGACGAAATGGTGGAGTCAAT                   GAAGAAAGAAGAAAACAAGGGAGGAGAAGACAAGCTAAAAATGATTCGGGAATATCGG                   CAAATGGTTGAGACTGAGCTAAAATTAATCTGTTGTGACATTCTGGATGTACTGGACA                   AACACCTCATTCCAGCAGCTAACACTGGCGAGTCCAAGGTTTTCTATTATAAAATGAA                   AGGGGACTACCACAGGTATCTGGCAGAATTTGCCACAGGAAACGACAGGAAGGAGGCT                   GCGGAGAACAGCCTAGTGGCTTATAAAGCTGCTAGTGATATTGCAACAATCCGTGGCT                   GCTCATTCTTGCCTACTTTACTCTCCCACTGA AGCAGGTTAGCGTTGAAGGTGGTATG                       GAAAAGCCTGCATGCCTGTTC                                       ORF Start: ATG at 95   ORF Stop: TGA at 494           SEQ ID NO:48   133 aa MW at 15309.2 kD                     NOV24a,   MDDREDLVYQAKLAEQAERYDEMVESMKKEENKGGEDKLKMIREYRQMVETELKLICC               CG107363-01   DILDVLDKHLIPAANTGESKVFYYKMKGDYHRYLAEFATGNDRKEAAENSLVAYKAAS               Protein Sequence   DIATIRGCSFLPTLLSH                                     SEQ ID NO:49   766 bp                     NOV24b,     ATGGCTGCCCGGACGCGGAGCGAGAGGGTGAAAAAAGTCGGAAACACTATCCGCTTCC                 CG107363-02     ATCCGTCGCGCAGACCCTGCCGGAGCCGCTGCCGCT ATGGATGATCGAGAGGATCTGG               DNA Sequence   TGTACCAGGCGAAGCTGGCCGAGCAGGCTGAGCGATACGACGAAATGGTGGAGTCAAT                   GAAGAAAGAAGAAAACAAGGGAGGAGAAGACAAGCTAAAAATGATTCGGGAATATCGG                   CAAATGGTTGAGACTGAGCTAAAATTAATCTGTTGTGACATTCTGGATGTACTGGACA                   AACACCTCATTCCAGCAGCTAACACTGGCGAGTCCAAGGTTTTCTATTATAAAATGAA                   AGGGGACTACCACAGGTATCTGGCAGAATTTGCCACAGGAAACGACAGGAAGGAGGCT                   GCGGAGAACAGCCTAGTGGCTTATAAAGCTGCTAGTGATATTGCAATGACAGAACTTC                   CACCAACGCATCCTATTCGCTTAGGTCTTGCTCTCAATTTTTCCGTATTCTACTACGA                   AATTCTTAATTCCCCTGACCGTGCCTGCAGGTTGGCAAAAGCAGCTTTTGATGATGCA                   ATTGCAGAACTGGATACGCTGAGTGAAGAAAGCTATAAGGACTCTACACTTATCATGC                   AGTTGTTACGTGATAATCTGACACTATGGACTTCAGACATGCAGGGTGACGGTGAAGA                   GCAGAATAAAGAAGCGCTGCAGGACGTGGAAGACGAAAATCAGTGA GACATAAGCCAA                       CAAGAGAAACCA                                       ORF Start: ATG at 95   ORF Stop: TGA at 740           SEQ ID NO:50   215 aa MW at 24688.4 kD                     NOV24b,   MDDREDLVYQAKLAEQAERYDEMVESMKKEENKGGEDKLKMIREYRQMVETELKLICC               CG107363-02   DILDVLDKHLIPAANTGESKVFYYKMKGDYHRYLAEFATGNDRKEAAENSLVAYKAAS               Protein Sequence   DIAMTELPPTHPIRLGLALNFSVFYYEILNSPDRACRLAKAAFDDAIAELDTLSEESY                   KDSTLIMQLLRDNLTLWTSDMQGDGEEQNKEALQDVEDENQ                                     SEQ ID NO:51   1084 bp                     NOV24c,     CGGCCGCGTCGACCATTTTTGCTGCCCGGACGCGGAGCGAGAGGCTGAGAGAGTCGGA                 CG107363-03     GACACTATCCGCTTCCATCCGTCGCGCAGACCCTGCCGGAGCCGCTGCCGCT ATGGAT               DNA Sequence   GATCGAGAGGATCTGGTGTACCAGGCGAAGCTGGCCGAGCAGGCTGAGCGATACGACG                   AAATGGTGGAGTCAATGAAGAAAGTAGCAGGGATGGATGTGGAGCTGACAGTTGAAGA                   AAGAAACCTCCTATCTGTTGCATATAAGAATGTGATTGGAGCTAGAAGAGCCTCCTGG                   AGAATAATCAGCAGCATTGAACAGAAAGAAGAAAACAAGGGAGGAGAAGACAAGCTAA                   AAATGATTCGGGAATATCGGCAAATGGTTGAGACTGAGCTAAAGTTAATCTGTTGTGA                   CATTCTGGATGTACTGGACAAACACCTCATTCCAGCAGCTAACACTGGCGAGTCCAAG                   GTTTTCTATTATAAAATGAAAGGGGACTACCACAGGTATCTGGCAGAATTTGCCACAG                   GAAACGACAGGAAGGAGGCTGCGGAGAACAGCCTAGTGGCTTATAAAGCTGCTAGTGA                   TATTGCAATGACAGAACTTCCACCAACGCATCCTATTCGCTTAGGTCTTGCTCTCAAT                   TTTTCCGTATTCTACTACGAAATTCTTAATTCCCCTGACCGTGCCTGCAGGTTGGCAA                   AAGCAGCTTTTGATGATGCAATTGCAGAACTGGATACGCTGAGTGAAGAAAGCTATAA                   GGACTCTACACTTATCATGCAGTTGTTACGTGATAATCTGACACTATGGACTTCAGAC                   ATGCAGGGTGACGATTCCTAA AGGAAAACCCAACTCTTCCTTTCCTAAAAACTCTACT                       TTGTGAAGAGCAGAATAAAGAAGCGCTGCAGGACGTGGAAGACGAAAATCAGTGAGAC                       ATAAGCCAACAAGAGAAACCATCTCTGACCACCCCCTCCTCCCCATCCCACCCTTTGG                       AAACTCCCCATTGTCACTGAGAACCACCAAATCTGACTTTTACATTTGGTCTCAGAAT                       TTAGGTTCCTGCCCTGTTGGTTTTTTTTTTTTTTTTTAAA                                       ORF Start: ATG at 111   ORF Stop: TAA at 831           SEQ ID NO:52   240 aa MW at 27418.7 kD                     NOV24c,   MDDREDLVYQAKLAEQAERYDEMVESMKKVAGMDVELTVEERNLLSVAYKNVIGARRA               CG107363-03   SWRIISSIEQKEENKGGEDKLKMIREYRQMVETELKLICCDILDVLDKHLIPAANTGE               Protein Sequence   SKVFYYKMKGDYHRYLAEFATGNDRKEAAENSLVAYKAASDIAMTELPPTHPIRLGLA                   LNFSVFYYEILNSPDRACRLAKAAFDDAIAELDTLSEESYKDSTLIMQLLRDNLTLWT                   SDMQGDDS                  
 
     [0421] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 24B.  
               TABLE 24B                          Comparison of NOV24a against NOV24b and NOV24c.                                     NOV24a   Identities/           Protein   Residues/   Similarities for the Matched           Sequence   Match Residues   Region                       NOV24b   1 . . . 119   119/119 (100%)               1 . . . 119   119/119 (100%)           NOV24c   1 . . . 119   119/159 (74%)                1 . . . 159   119/159 (74%)                       
 
     [0422] Further analysis of the NOV24a protein yielded the following properties shown in Table 24C.  
               TABLE 24C                       Protein Sequence Properties NOV24a                                        PSort   0.4500 probability located in cytoplasm; 0.3000 probability       analysis:   located in microbody (peroxisome); 0.1000           probability located in mitochondrial matrix           space; 0.1000 probability located in           lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0423] A search of the NOV24a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 24D.  
               TABLE 24D                          Geneseq Results for NOV24a                                         NOV24a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               ABG00586   Novel human diagnostic protein   1 . . . 119   119/159 (74%)   7e−58           #577 -  Homo sapiens , 255 aa.   1 . . . 159   119/159 (74%)           [WO200175067-A2, 11-OCT-2001]       ABG00586   Novel human diagnostic protein   1 . . . 119   119/159 (74%)   7e−58           #577 -  Homo sapiens , 255 aa.   1 . . . 159   119/159 (74%)           [WO200175067-A2, 11-OCT-2001]       AAY92333   Human 14-3-3-epsilon -  Homo     1 . . . 119   119/159 (74%)   7e−58             sapiens , 255 aa. [WO200020448-   1 . . . 159   119/159 (74%)           A2, 13-APR-2000]       AAY13596   Cruciform binding protein (CBP) -   1 . . . 119   119/159 (74%)   7e−58             Ovis ammon  aries, 255 aa.   1 . . . 159   119/159 (74%)           [WO9928340-A2, 10-JUN-1999]       AAB56772   Human prostate cancer antigen   1 . . . 119   118/159 (74%)   3e−57           protein sequence SEQ ID NO: 1350 -   42 . . . 200    118/159 (74%)             Homo sapiens , 296 aa.           [WO200055174-A1, 21-SEP-2000]                  
 
     [0424] In a BLAST search of public sequence datbases, the NOV24a protein was found to have homology to the proteins shown in the BLASTP data in Table 24E.  
               TABLE 24E                          Public BLASTP Results for NOV24a                                         NOV24a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               P42655   14-3-3 protein epsilon   1 . . . 119   119/159 (74%)   2e−57           (Mitochondrial import stimulation   1 . . . 159   119/159 (74%)           factor L subunit) (Protein kinase C           inhibitor protein-1) (KCIP-1) (14-3-           3E) -  Homo sapiens  (Human), 255           aa.       S23303   protein kinase C inhibitor KCIP-1   1 . . . 112   112/152 (73%)   7e−54           isoform epsilon - sheep, 212 aa.   1 . . . 152   112/152 (73%)       O57468   14-3-3 PROTEIN EPSILON -   1 . . . 119   111/159 (69%)   3e−52             Xenopus laevis  (African clawed   1 . . . 159   116/159 (72%)           frog), 255 aa.       P92177   14-3-3 protein epsilon (Suppressor of   1 . . . 119    94/159 (59%)   6e−43           RAS1 3-9) -  Drosophila     1 . . . 159   108/159 (67%)             melanogaster  (Fruit fly), 260 aa.       Q9UR29   14-3-3 -  Lentinula edodes  (Shiitake   2 . . . 119    86/158 (54%)   1e−37           mushroom) (Lentinus edodes), 256   3 . . . 160   102/158 (64%)           aa.                  
 
     [0425] PFam analysis predicts that the NOV24a protein contains the domains shown in the Table 24F.  
               TABLE 24F                          Domain Analysis of NOV24a                                 NOV24a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               14-3-3   4 . . . 28   21/25 (84%)   1.9e−09                25/25 (100%)       14-3-3   29 . . . 120   64/92 (70%)   6.1e−40               88/92 (96%)                  
 
     Example 25  
     [0426] The NOV25 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 25A.  
               TABLE 25A                       NOV25 Sequence Analysis                                                SEQ ID NO:53   3439 bp                     NOV25a,     CGGGGGCGGGGGGTGGGCGGGGCCGGGCGCCGCCGCGGAGCCTCCCGGGCCGCCGCGA                 CG108360-01     TC ATGTCGGACCAGGCGCCCAAAGTTCCTGAGGAGATGTTCAGGGAGGTCAAGTATTA               DNA Sequence   CGCGGTGGGCGACATCGACCCGCAGGTTATTCAGCTTCTCAAGGCTGGAAAAGCGAAG                   GAAGTTTCCTACAATGCACTAGCCTCACACATAATCTCAGAGGATGGGGACAATCCAG                   AGGTGGGAGAAGCTCGGGAAGTCTTTGACTTACCTGTTGTAAAGCCTTCTTGGGTGAT                   TCTGTCCGTTCAGTGTGGAACTCTTCTGCCAGTAAATGGTTTTTCTCCAGAATCATGT                   CAGATTTTTTTTGGAATCACTGCCTGCCTTTCTCAGGTGTCATCTGAAGACAGAAGTG                   CCCTGTGGGCTTTGGTTACGTTCTATGGGGGAGATTGCCAGCTAACCCTCAATAAGAA                   ATGCACGCATTTGATTGTTCCAGAGCCAAAGGGGGAGAAATACGAATGTGCTTTAAAG                   CGAGCAAGTATTAAAATTGTGACTCCTGACTGGGTTCTGGATTGCGTATCAGAGAAAA                   CCAAAAAGGACGAAGCATTTTATCATCCTCGTCTGATTATTTATGAAGAGGAAGAAGA                   GGAAGAGGAAGAGGAGGAGGAAGTAGAAAATGAGGAACAAGATTCTCAGAATGAGGGT                   AGTACAGATGAGAAGTCAAGCCCTGCCAGCTCTCAAGAAGGGTCTCCTTCAGGTGACC                   AGCAGTTTTCACCTAAATCCAACACTGAAAAATCTAAAGGGGAATTAATGTTTGATGA                   TTCTTCAGATTCATCACCGGAAAAACAGGAGAGAAATTTAAACTGGACCCCGGCCGAA                   GTCCCACAGTTAGCTGCAGCAAAACGCAGGCTGCCTCAGGGAAAGGAGCCTGGGTTGA                   TTAACTTGTGTGCCAATGTCCCACCCGTCCCAGGTAACATTTTGCCCCCTGAGGTCCG                   GGGTAATTTAATGGCTGCTGGACAAAACCTCCAAAGTTCTGAAAGATCAGAAATGATA                   GCTACCTGGAGTCCAGCTGTACGGACACTGAGGAATATTACTAATAATGCTGACATTC                   AGCAGATGAACCGGCCATCAAATGTAGCACATATCTTACAGACTCTTTCAGCACCTAC                   GAAAAATTTAGAACAGCAGGTGAATCACAGCCAGCAGGGACATACAAATGCCAATGCA                   GTGCTGTTTAGCCAAGTGAAAGTGACTCCAGAGACACACATGCTACAGCAGCAGCAGC                   AGGCCCAGCAGCAGCAGCAGCAGCACCCGGTTTTACACCTTCAGCCCCAGCAGATAAT                   GCAGCTCCAGCAGCAGCAGCAGCAGCAGATCTCTCAGCAACCTTACCCCCAGCAGCCG                   CCGCATCCATTTTCACAGCAACAGCAGCAGCAGCAGCAAGCCCATCCGCATCAGTTTT                   CACAGCAACAGCTACAGTTTCCACAGCAACAGTTGCATCCTCCACAGCAGCTGCATCG                   CCCTCAGCAGCAGCTCCAGCCCTTTCAGCAGCAGCATGCCCTGCAGCAGCAGTTCCAT                   CAGCTGCAGCAGCACCAGCTCCAGCAGCAGCAGCTTGCCCAGCTCCAGCAGCAGCACA                   GCCTGCTCCAGCAGCAGCAGCAACAGCAGATTCAGCAGCAGCAGCTCCAGCGCATGCA                   CCAGCAGCAGCAGCAGCAGCAGATGCAAAGTCAGACAGCGCCACACTTGAGTCAGACG                   TCACAGGCGCTGCAGCATCAGGTTCCACCTCAGCAGCCCCCGCAGCAGCAGCAGCAAC                   AGCAGCCACCACCATCGCCTCAGCAGCATCAGCTTTTTGGACATGATCCAGCAGTGGA                   GATTCCAGAAGAAGGCTTCTTATTGGGATGTGTGTTTGCAATTGCGGATTATCCAGAG                   CAGATGTCTGATAAGCAACTGCTGGCCACCTGGAAAAGGATAATCCAGGCACATGGCG                   GCACTGTTGACCCCACCTTCACGAGTCGATGCACGCACCTTCTCTGTGAGAGTCAAGT                   CAGCAGCGCGTATGCACAGGCAATAAGAGAAAGAAAGAGATGTGTTACTGCACACTGG                   TTAAACACAGTCTTAAAGAAGAAGAAAATGGTACCGCCGCACCGAGCCCTTCACTTCC                   CAGTGGCCTTCCCACCAGGAGGAAAGCCATGTTCACAGCATATTATTTCTGTGACTGG                   ATTTGTTGATAGTGACAGAGATGACCTAAAATTAATGGCTTATTTGGCAGGTGCCAAA                   TATACGGGTTATCTATGCCGCAGCAACACAGTCCTCATCTGTAAAGAACCAACTGGTT                   TAAAGTATGAAAAAGCCAAAGAGTGGAGGATACCCTGTGTCAACGCCCAGTGGCTTGG                   CGACATTCTTCTGGGAAACTTTGAGGCACTGAGGCAGATTCAGTATAGTCGCTACACG                   GCATTCAGTCTGCAGGATCCATTTGCCCCTACCCAGCATTTAGTTTTAAATCTTTTAG                   ATGCTTGGAGAGTTCCCTTAAAAGTGTCTGCAGAGTTGTTGATGAGTATAAGACTACC                   TCCCAAACTGAAACAGAATGAAGTAGCTAATGTCCAGCCTTCTTCCAAAAGAGCCAGA                   ATTGAAGACGTACCACCTCCCACTAAAAAGCTAACTCCAGAATTGACCCCTTTTGTGC                   TTTTCACTGGATTCGAGCCTGTCCAGGTTCAACAGTATATTAAGAAGCTCTACATTCT                   TGGTGGAGAGGTTGCGGAGTCTGCACAGAAGTGCACACACCTCATTGCCAGCAAAGTG                   ACTCGCACCGTGAAGTTCCTGACGGCGATTTCTGTCGTGAAGCACATAGTGACGCCAG                   AGTGGCTGGAAGAATGCTTCAGGTGTCAGAAGTTCATTGATGAGCAGAACTACATTCT                   CCGAGATGCTGAGGCAGAAGTACTTTTCTCTTTCAGCTTGGAAGAATCCTTAAAACGG                   GCACACGTTTCTCCACTCTTTAAGGCAAAATATTTTTACATCACACCTGGAATCTGCC                   CAAGTCTTTCCACTATGAAGGCAATCGTAGAGTGTGCAGGAGGAAAGGTGTTATCCAA                   ATTTTAATATCCTGTGAAAATGACCTTCATTTATGCCGAGAATATTTTGCCAGAGGCA                   TAGATGTTCACAATGCAGAGTTCGTTCTGACTGGAGTGCTCACTCAAACGCTGGACTA                   TGAATCATATAAGTTTAACTGA TGGCGTCTAGGCTGCCGTGCATGTCGACTCCTGCGG                       TGCGGGGCTGGCTGTCTGGCTGGCGAGGAGCTGCTGCGCTTCCTTCACATGCTCTTGT                       TTTCCAGCTGCTTTCCTGGGGGATCAGACTGTGAAGCAGGAAGACAGATATAATAAAT                       ATACTGCATCTTTTTAA                                       ORF Start: ATG at 61   ORF Stop: TGA at 3268           SEQ ID NO:54   1069 aa MW at 121340.7 kD                     NOV25a,   MSDQAPKVPEEMFREVKYYAVGDIDPQVIQLLKAGKAKEVSYNALASHIISEDGDNPE               CG108360-01   VGEAREVFDLPVVKPSWVILSVQCGTLLPVNGFSPESCQIFFGITACLSQVSSEDRSA               Protein Sequence   LWALVTFYGGDCQLTLNKKCTHLIVPEPKGEKYECALKRASIKIVTPDWVLDCVSEKT                   KKDEAFYHPRLIIYEEEEEEEEEEEEVENEEQDSQNEGSTDEKSSPASSQEGSPSGDQ                   QFSPKSNTEKSKGELMFDDSSDSSPEKQERNLNWTPAEVPQLAAAKRRLPQGKEPGLI                   NLCANVPPVPGNILPPEVRGNLMAAGQNLQSSERSEMIATWSPAVRTLRNITNNADIQ                   QMNRPSNVAHILQTLSAPTKNLEQQVNHSQQGHTNANAVLFSQVKVTPETHMLQQQQQ                   AQQQQQQHPVLHLQPQQIMQLQQQQQQQISQQPYPQQPPHPFSQQQQQQQQAHPHQFS                   QQQLQFPQQQLHPPQQLHRPQQQLQPFQQQHALQQQFHQLQQHQLQQQQLAQLQQQHS                   LLQQQQQQQIQQQQLQRMHQQQQQQQMQSQTAPHLSQTSQALQHQVPPQQPPQQQQQQ                   QPPPSPQQHQLFGHDPAVEIPEEGFLLGCVFAIADYPEQMSDKQLLATWKRIIQAHGG                   TVDPTFTSRCTHLLCESQVSSAYAQAIRERKRCVTAHWLNTVLKKKKMVPPHRALHFP                   VAFPPGGKPCSQHIISVTGFVDSDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPTGL                   KYEKAKEWRIPCVNAQWLGDILLGNFEALRQIQYSRYTAFSLQDPFAPTQHLVLNLLD                   AWRVPLKVSAELLMSIRLPPKLKQNEVANVQPSSKRARIEDVPPPTKKLTPELTPFVL                   FTGFEPVQVQQYIKKLYILGGEVAESAQKCTHLIASKVTRTVKFLTAISVVKHIVTPE                   WLEECFRCQKFIDEQNYILRDAEAEVLFSFSLEESLKRAHVSPLFKAKYFYITPGICP                   SLSTMKAIVECAGGKVLSKQPSFRKLMEHKQNSSLSEIILISCENDLHLCREYFARGI                   DVHNAEFVLTGVLTQTLDYESYKFN                  
 
     [0427] Further analysis of the NOV25a protein yielded the following properties shown in Table 25B.  
               TABLE 25B                       Protein Sequence Properties NOV25a                                        PSort   0.9400 probability located in nucleus; 0.1000 probability       analysis:   located in mitochondrial matrix space; 0.1000 probability           located in lysosome (lumen); 0.0000 probability           located in endoplasmic reticulum (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0428] A search of the NOV25a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 25C.  
               TABLE 25C                          Geneseq Results for NOV25a                                         NOV25a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAU27822   Human full-length polypeptide    466 . . . 1069   535/610 (87%)   0.0           sequence #147 -  Homo sapiens ,   314 . . . 911   546/610 (88%)           911 aa. [WO200164834-A2, 07-SEP-2001]       ABB71695     Drosophila melanogaster      385 . . . 1064   244/730 (33%)   2e−91           polypeptide SEQ ID NO: 41877 -   1073 . . . 1777   355/730 (48%)             Drosophila melanogaster , 1798 aa.           [WO200171042-A2, 27-SEP-2001]       ABB58382     Drosophila melanogaster     342 . . . 586    93/258 (36%)   3e−25           polypeptide SEQ ID NO: 1938 -    31 . . . 267   116/258 (44%)             Drosophila melanogaster , 3502 aa.           [WO200171042-A2, 27-SEP-2001]       ABB71160     Drosophila melanogaster     208 . . . 590   110/401 (27%)   7e−24           polypeptide SEQ ID NO: 40272 -   3557 . . . 3949   167/401 (41%)             Drosophila melanogaster , 5560 aa.           [WO200171042-A2, 27-SEP-2001]       ABB65772     Drosophila melanogaster     208 . . . 590   110/401 (27%)   7e−24           polypeptide SEQ ID NO: 24108 -   3557 . . . 3949   167/401 (41%)             Drosophila melanogaster , 5533 aa.           [WO200171042-A2, 27-SEP-2001]                  
 
     [0429] In a BLAST search of public sequence datbases, the NOV25a protein was found to have homology to the proteins shown in the BLASTP data in Table 25D.  
               TABLE 25D                          Public BLASTP Results for NOV25a                                         NOV25a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                             Q9Z0W6   PAX TRANSCRIPTION    1 . . . 1069   916/1077   (85%)   0.0           ACTIVATION DOMAIN    1 . . . 1056   960/1077   (89%)           INTERACTING PROTEIN PTIP           -  Mus musculus  (Mouse), 1056 aa.       O15404   CAGF28 -  Homo sapiens      466 . . . 1069   514/610   (84%)   0.0           (Human), 744 aa (fragment).   147 . . . 744    529/610   (86%)       Q90WJ3   SWIFT -  Xenopus laevis  (African   333 . . . 1068   513/795   (64%)   0.0           clawed frog), 1256 aa.   472 . . . 1255   575/795   (71%)       Q96HP2   UNKNOWN (PROTEIN FOR   679 . . . 1069   391/391   (100%)   0.0           IMAGE:3503689) -  Homo sapiens       1 . . . 391   391/391   (100%)           (Human), 391 aa (fragment).       Q9VUB6   CG8797 PROTEIN -  Drosophila      385 . . . 1064   244/730   (33%)   4e−91             melanogaster  (Fruit fly), 1798 aa.   1073 . . . 1777    355/730   (48%)                  
 
     [0430] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25E.  
               TABLE 25E                          Domain Analysis of NOV25a                                     Identifies/                   Similarities           NOV25a   for the       Pfam Domain   Match Region   Matched Region   Expect Value                                         BRCT   10 . . . 93   15/101   (15%)   1.2e−08               59/101   (58%)       BRCT    96 . . . 183   35/101   (35%)   2.3e−25               64/101   (63%)       BRCT   603 . . . 694   24/102   (24%)   1.8e−17               69/102   (68%)       BRCT   703 . . . 776   25/88   (28%)   2.3e−18               64/88   (73%)       BRCT   869 . . . 947   23/93   (25%)   1.9e−17               67/93   (72%)       BRCT    970 . . . 1053   19/98   (19%)   0.27               56/98   (57%)                  
 
     Example 26  
     [0431] The NOV26 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 26A.  
               TABLE 26A                       NOV26 Sequence Analysis                                                SEQ ID NO:55   368 bp                     NOV26a,     G ATGAAATTCGTGTACAAAGAAGAGCATCCGTTCAAGAAACGGGCGTCCGAGAGCAAG               CG108762-01   AAGACTGGAAAGAAATACCCGGACCGGGTGCCGGTGATAGTAGAAAAGGCTCCCAAAG               DNA Sequence   CTCGGATAGGAGACCTGGACCAAAAGAAATACCTGGTGCCTTCTGATCTCACAGCTGG                   TCAGTTCTACTTCTTGATCCAGAAGCGAATTCATCTCCGAGCTGAGGATGCCTTGTTT                   TTCTTTGTCAACAATGTCATTCTGCCCACCAGTGCCACAATGGGTCAGCTCTACCAGG                   AACACCATGAAGACTTCTTTCTCTACGTTGCCTACAGTGACCAAAGTGTCTACAGTCT                   GTGA TGCTGCTACCCCTGAG                                       ORF Start: ATG at 2   ORF Stop: TGA at 350           SEQ ID NO:56   116 aa MW at 13595.5 kD                     NOV26a,   MKFVYKEEHPFKKRASESKKTGKKYPDRVPVIVEKAPKARIGDLDQKKYLVPSDLTAG               CG108762-01   QFYFLIQKRIHLRAEDALFFFVNNVILPTSATMGQLYQEHHEDFFLYVAYSDQSVYSL       Protein Sequence                  
 
     [0432] Further analysis of the NOV26a protein yielded the following properties shown in Table 26B.  
               TABLE 26B                       Protein Sequence Properties NOV26a                                        PSort   0.6400 probability located in microbody (peroxisome);       analysis:   0.4500 probability           located in cytoplasm; 0.1000 probability located in mito-           chondrial matrix           space; 0.1000 probability located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0433] A search of the NOV26a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 26C.  
               TABLE 26C                          Geneseq Results for NOV26a                                         NOV26a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value                                             AAG03859   Human secreted protein, SEQ ID   1 . . . 116   103/117   (88%)   9e−55           NO: 7940 -  Homo sapiens , 117 aa.   1 . . . 117   109/117   (93%)           [EP1033401-A2, 06 Sep. 2000]       AAG03857   Human secreted protein, SEQ ID   1 . . . 116   103/117   (88%)   9e−55           NO: 7938 -  Homo sapiens , 117 aa.   1 . . . 117   109/117   (93%)           [EP1033401-A2, 06 Sep. 2000]       ABB58226     Drosophila melanogaster     1 . . . 116   94/117   (80%)   4e−50           polypeptide SEQ ID NO 1470 -   1 . . . 117   104/117   (88%)             Drosophila melanogaster , 121 aa.           [WO200171042-A2, 27 Sep. 2001]       AAM00990   Human bone marrow protein, SEQ   1 . . . 114   90/115   (78%)   9e−48           ID NO: 491 -  Homo sapiens , 117   1 . . . 115   102/115   (88%)           aa. [WO200153453-A2, 26 Jul.           2001]       AAM00943   Human bone marrow protein, SEQ   1 . . . 114   90/115   (78%)   9e−48           ID NO: 419 -  Homo sapiens , 144   28 . . . 142    102/115   (88%)           aa. [WO200153453-A2, 26 Jul.           2001]                  
 
     [0434] In a BLAST search of public sequence datbases, the NOV26a protein was found to have homology to the proteins shown in the BLASTP data in Table 26D.  
               TABLE 26D                          Public BLASTP Results for NOV26a                                         NOV26a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                             O95166   MM46 (HT004 PROTEIN) (MAP1   1 . . . 116   103/117   (88%)   2e−54           LIGHT CHAIN 3 RELATED   1 . . . 117   109/117   (93%)           PROTEIN) -  Homo sapiens  (Human),           117 aa.       Q9DCD6   GAMMA-AMINOBUTYRIC ACID   1 . . . 116   103/117   (88%)   4e−54           RECEPTOR ASSOCIATED   1 . . . 117   108/117   (92%)           PROTEIN -  Mus musculus  (Mouse),           117 aa.       Q9DFN7   GABA(A) RECEPTOR   1 . . . 114   99/115   (86%)   6e−52           ASSOCIATED PROTEIN -   1 . . . 115   105/115   (91%)             Gillichthys mirabilis  (Long-jawed           mudsucker), 122 aa.       Q9W2S2   CG1534 PROTEIN -  Drosophila      1 . . . 116   94/117   (80%)   1e−49             melanogaster  (Fruit fly), 121 aa.   1 . . . 117   104/117   (88%)       Q9H0R8   HYPOTHETICAL 14.0 KDA   1 . . . 114   90/115   (78%)   2e−47           PROTEIN (GABA-A RECEPTOR-   1 . . . 115   102/115   (88%)           ASSOCIATED PROTEIN LIKE 1)           (EARLY ESTROGEN-           REGULATED PROTEIN) (RIKEN           CDNA 9130422N19 GENE) -  Homo                sapiens  (Human), 117 aa.                  
 
     [0435] PFam analysis predicts that the NOV26a protein contains the domains shown in the Table 26E.  
               TABLE 26E                          Domain Analysis of NOV26a                                     Identities/               NOV26a   Similarities for       Pfam Domain   Match Region   the Matched Region   Expect Value               MAP1_LC3   13 . . . 115   59/106 (56%)   1.4e−57               89/106 (84%)                  
 
     Example 27  
     [0436] The NOV27 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 27A.  
               TABLE 27A                       NOV27 Sequence Analysis                                                SEQ ID NO:57   1504 bp                     NOV27a,     ACGCGTCCGGTTCGCTCTGAGTCGCGTGGCAGGCCGCGCTGCGTCCACCGCTGCCGAG                 CG108829-01     TTCAGAGCCGCGCACCGCCCGCCGCCGCAGGTCGGGTTCCCAGCGCTACTCCCAAGAC                 DNA Sequence     ACCGCTCAGCC ATGAAGATGCATTTCTGTATCCCGGTGTCCCAGCAGCGGTCCGACGC                   GCTGGGGGGCCGCTACGTGCTGTACTCCGTGCACCTGGACGGGTTCCTCTTCTGCAGG                   GTGCGCTACAGCCAGCTGCACGGTTGGAACGAACAGCTAAGGCGGGTCTTTGGAAATT                   GCCTGCCACCCTTCCCACCAAAGTACTATCTGGCAATGACCACAGCTATGGCTGATGA                   GAGGAGGGACCAACTGGAACAATATTTGCAAAATGTAACCATGGACCCAAACGTGTTG                   AGAAGTGATGTCTTCGTTGAGTTTTTAAAACTGGCGCAGCTGAATACATTTGACATCG                   CCACCAAGAAAGCTTATCTGGACATATTTCTGCCCAATGAACAGAGTATTAGAATCGA                   AATTATAACATCAGACACTGCTGAAAGAGTCCTAGAGGTGGTGTCACACAAAATTGGA                   CTGTGTCGAGAGCTCTTGGGCTACTTCGGCCTCTTTCTCATTCGGTTTGGCAAGGAGG                   GCAAGCTCTCTGTTGTGAAAAAATTGGCTGACTTTGAACTCCCTTATGTTAGTCTTGG                   AAGTTCTGAGGTGGAAAACTGTAAGGTTGGACTCCGAAAGTGGTATATGGCTCCATCC                   CTCGACTCCGTGCTGATGGACTGCAGGGTGGCGGTAGATTTGCTCTACATGCAGGCAA                   TACAGGACATTGAAAAAGGATGGGCCAAACCCACACAGGCACAGAGGCAGAAATTAGA                   AGCTTTCCAGAAAGAAGACAGTCAAACAAAGTTTTTGGAGCTGGCCCGGGAGGTACGG                   CACTATGGATACCTGCAGCTGGATCCTTGTACCTGTGACTACCCAGAATCAGGCTCTG                   GAGCTGTTCTTTCTGTTGGCAATAATGAGATCAGCTGCTGCATCACCCTGCCTGACAG                   CCAGACCCAGGACATCGTTTTCCAGATGAGCAGGGTGAAGTGCTGGCAGGTCACTTTC                   CTTGGAACTCTGCTGGATACGGATGGGCCCCAGAGAACTCTCAACCAGAACTTAGAGC                   TCAGATTTCAATACAGTGAGGATAGTTGCTGGCAGTGGTTTGTTATTTACACCAAACA                   GGCTTTTTTGCTGAGTAGTTGCTTGAAAAAGATGATCTCAGAAAAGATGGTAAAGCTA                   GCTGCTGAGAATACAGAAATGCAGATTGAAGTTCCGGAACAAAGCAAAAGTAAAAAAT                   ACCACATTCAACAAAGCCAGAAAGACTATTCTAGTTTTCTATCAAGAAAAAGCAAGAT                   TAAGATAGCTAAAGGTGACTGCGTTTTTGGGAACATAAAGGAAGAAGATCTCTGA AGA                       AAGCTCTCATATTTTAAAATATCCTTGGAGGCTATCTCAAGACAGTGAAAGAAC                                       ORF Start: ATG at 128   ORF Stop: TGA at 1445           SEQ ID NO:58   439 aa MW at 50614.8 kD                     NOV27a,   MKMHFCIPVSQQRSDALGGRYVLYSVHLDGFLFCRVRYSQLHGWNEQLRRVFGNCLPP               CG108829-01   FPPKYYLAMTTAMADERRDQLEQYLQNVTMDPNVLRSDVFVEFLKLAQLNTFDIATKK               Protein Sequence   AYLDIFLPNEQSIRIEIITSDTAERVLEVVSHKIGLCRELLGYFGLFLIRFGKEGKLS                   VVKKLADFELPYVSLGSSEVENCKVGLRKWYMAPSLDSVLMDCRVAVDLLYMQAIQDI                   EKGWAKPTQAQRQKLEAFQKEDSQTKFLELAREVRHYGYLQLDPCTCDYPESGSGAVL                   SVGNNEISCCITLPDSQTQDIVFQMSRVKCWQVTFLGTLLDTDGPQRTLNQNLELRFQ                   YSEDSCWQWFVIYTKQAFLLSSCLKKMISEKMVKLAAENTEMQIEVPEQSKSKKYHIQ                   QSQKDYSSFLSRKSKIKIAKGDCVFGNIKEEDL                  
 
     [0437] Further analysis of the NOV27a protein yielded the following properties shown in Table 27B.  
               TABLE 27B                       Protein Sequence Properties NOV27a                                        PSort   0.4500 probability located in cytoplasm; 0.1000 probability       analysis:   located in mitochondrial matrix space;           0.1000 probability located in lysosome (lumen);           0.0782 probability located in microbody (peroxisome)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0438] A search of the NOV27a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 27C.  
               TABLE 27C                          Geneseq Results for NOV27a                                         NOV27a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value                                             ABB61758     Drosophila melanogaster      2 . . . 400   133/416   (31%)   5e−52           polypeptide SEQ ID NO 12066 -    5 . . . 407   222/416   (52%)             Drosophila melanogaster , 490 aa.           [WO200171042-A2, 27 Sep. 2001]       AAB54165   Human pancreatic cancer antigen   20 . . . 253   104/235   (44%)   6e−52           protein sequence SEQ ID NO:617 -   50 . . . 284   153/235   (64%)             Homo sapiens , 288 aa.           [WO200055320-A1, 21 Sep. 2000]       ABB59662     Drosophila melanogaster     18 . . . 379   87/368   (23%)   1e−20           polypeptide SEQ ID NO 5778 -   82 . . . 424   160/368   (42%)             Drosophila melanogaster , 431 aa.           [WO200171042-A2, 27 Sep. 2001]       AAM41948   Human polypeptide SEQ ID NO   95 . . . 378   65/289   (22%)   3e−15           6879 -  Homo sapiens , 280 aa.    7 . . . 272   126/289   (43%)           [WO200153312-A1, 27 Jul. 2001]       AAM40162   Human polypeptide SEQ ID NO   119 . . . 378    59/265   (22%)   5e−14           3307 -  Homo sapiens , 284 aa.   20 . . . 263   115/265   (43%)           [WO200153312-A1, 26 Jul. 2001]                  
 
     [0439] In a BLAST search of public sequence datbases, the NOV27a protein was found to have homology to the proteins shown in the BLASTP data in Table 27D.  
               TABLE 27D                          Public BLASTP Results for NOV27a                                         NOV27a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value                                             Q9D690   4631426E05RIK PROTEIN    3 . . . 439   330/437   (75%)   0.0             Mus musculus  (Mouse), 436 aa.   1 . . . 436   381/437   (86%)       Q15036   Sorting nexin 17 -  Homo sapiens      3 . . . 425   175/434   (40%)   6e−85           (Human), 470 aa.   1 . . . 433   267/434   (61%)       AAH26571   SIMILAR TO SORTING NEXIN   3 . . . 425   175/434   (40%)   1e−84           17 -  Mus musculus  (Mouse), 470   1 . . . 433   266/434   (60%)           aa.       Q9VL28   CG5734 PROTEIN (LD15323P) -   2 . . . 400   133/416   (31%)   1e−51             Drosophila melanogaster  (Fruit   5 . . . 407   222/416   (52%)           fly), 490 aa.       Q19532   Hypothetical 54.2 kDa protein   12 . . . 410    102/423   (24%)   2e−34           F17H10.3 in chromosome X -   14 . . . 419    204/423   (48%)             Caenorhabditis elegans , 463 aa.                  
 
     [0440] PFam analysis predicts that the NOV27a protein contains the domains shown in the Table 27E.  
               TABLE 27E                          Domain Analysis of NOV27a                                     Identities/               NOV27a   Similarities for       Pfam Domain   Match Region   the Matched Region   Expect Value               PX   1 . . . 105   30/133 (23%)   3.2e−09               70/133 (53%)                  
 
     Example 28  
     [0441] The NOV28 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 28A.  
               TABLE 28A                       NOV28 Sequence Analysis                                                SEQ ID NO:59   3534 bp                     NOV28a,     GAGCCCGGCCGGGATGAGAAGGTGACGCCGCCGGGGGCGCCACTCGCTTTGTGGGGGA                 CG108861-01     AG ATGCTCGCCTACTGCGTGCAGGATGCCACCGTGGTGGACGTGGAGAAGCGGAGGAA               DNA Sequence   CCCCTCCAAGCACTACGTGAGTACACCACAGGTATACATAATCAATGTGACCTGGTCT                   GACTCCACCTCCCAGACTATCTACCGGAGGTACAGCAAGTTCTTTGACCTGCAGATGC                   AGCTTTTGGATAAGTTTCCCATTGAAGGTGGCCAGAAGGACCCCAAGCAAAGGATCAT                   CCCCTTCCTCCCAGGCAAGATCCTCTTCCGCAGAAGCCACATCCGGGACGTAGCTGTG                   AAGAGACTGAAGCCCATCGATGAATACTGCCGGGCACTTGTCCGGCTGCCCCCCCACA                   TCTCACAGTGTGACGAAGTCTTCCGGTTCTTCGAGGCTCGACCCGAGGATGTCAACCC                   TCCAAAAGAGGACTATGGCAGTTCCAAGAGGAAATCAGTGTGGCTGTCCAGCTGGGCT                   GAGTCGCCCAAGAAGGACGTGACAGGTGCCGACGCCACCGCCGAGCCCATGATCCTGG                   AACAGTACGTGGTGGTGTCCAACTATAAGAAGCAGGAGAACTCGGAGCTGAGCCTCCA                   GGCCGGGGAGGTGGTGGATGTCATCGAGAAGAACGAGAGCGGCTGGTGGTTCGTGAGC                   ACTTCTGAGGAGCAGGGCTGGGTCCCTGCCACCTACCTGGAGGCCCAGAATGGTACTC                   GGGATGACTCCGACATCAACACCTCTAAGACTGGAGAAGTGTCCAAGAGACGCAAGGC                   CCATCTGCGGCGCCTGGATCGCCGGTGGACCCTGGGCGGGATGGTCAACAGGCAGCAC                   AGCCGAGAGGAGAAGTATGTCACCGTGCAGCCTTACACCAGCCAAAGCAAGGACGAGA                   TTGGCTTTGAGAAGGGCGTCACAGTGGAGGTGATCCGGAAGAATCTGGAAGGCTGGTG                   GTATATCAGATACCTGGGCAAAGAGGGCTGGGCGCCAGCATCCTACCTGAAGAAGGCC                   AAGGATGACCTGCCAACCCGGAAGAAGAACCTGGCCGGCCCAGTGGAGATCATTGGGA                   ACATCATGGAGATCAGCAACCTGCTGAACAAGAAGGCGTCTGGGGACAAGGAAACTCC                   ACCAGCCGAAGGCGAGGGCCATGAGGCCCCCATTGCCAAGAAGGAGATCAGCCTGCCC                   ATCCTCTGCAATGCCTCCAATGGCAGTGCCGTGGGCGTTCCTGACAGGACTGTCTCCA                   GGCTGGCCCAGGGCTCTCCAGCTGTGGCCAGGATTGCCCCTCAGCGGGCCCAGATCAG                   CTCCCCGAACCTACGGACAAGACCTCCACCACGCAGAGAATCCAGCCTGGGGTTCCAA                   CTGCCAAAGCCACCAGAGCCCCCTTCTGTTGAGGTGGAGTACTACACCATTGCCGAAT                   TCCAGTCGTGCATTTCCGATGGCATCAGCTTTCGGGGTGGACAGAAGGCAGAGGTCAT                   TGATAAGAACTCAGGTGGCTGGTGGTACGTGCAGATCGGTGAGAAGGAGGGCTGGGCC                   CCCGCATCATACATCGATAAGCGCAAGAAGCCCAACCTGAGCCGCCGCACAAGCACGC                   TGACCCGGCCCAAGGTGCCCCCGCCAGCACCCCCCAGCAAGCCCAAGGAGGCCGAGGA                   GGGCCCTACGGGGGCCAGTGAGAGCCAGGACTCCCCGCGGAAGCTCAAGTATGAGGAG                   CCTGAGTATGACATCCCTGCATTCGGCTTTGACTCAGAGCCTGAGCTGAGCGAGGAGC                   CCGTGGAGGACAGAGCCTCAGGGGAGAGGCGGCCTGCCCAGCCCCACCGGCCCTCGCC                   GGCCTCTTCTCTGCAGCGGGCCCGCTTCAAGGTGGGTGAGTCTTCAGAGGATGTGGCC                   CTGGAAGAGGAGACCATCTATGAGAATGAGGGCTTCCGGCCATATGCAGAGGACACCC                   TGTCAGCCAGAGGCTCCTCCGGGGACAGCGACTCCCCAGGCAGCTCCTCGCTGTCCCT                   GACCAGGAAAAACTCCCCCAAATCAGGCTCCCCCAAGTCATCATCACTCCTAAAGCTC                   AAGGCAGAGAAGAATGCCCAGGCAGAAATGGGGAAGAACCACTCCTCAGCCTCCTTTT                   CCTCATCCATCACCATCAACACCACTTGCTGCTCCTCCTCTTCCTCCTCCTCCTCTTC                   CTTGTCCAAAACCAGTGGCGACCTGAAGCCCCGCTCTGCTTCGGACGCAGGCATCCGC                   GGCACTCCCAAGGTCAGGGCAAAGAAGGATGCTGATGCGAACGCTGGGCTGACCTCCT                   GTCCCCGGGCCAAGCCATCGGTCCGGCCCAAGCCATTCCTAAACCGAGCAGAGTCGCA                   GAGCCAAGAGAAGATGGACATCAGCACTTTACGGCGCCAGCTGAGACCCACAGGCCAG                   CTCCGTGGAGGGCTCAAGGGCTCCAAGAGTGAGGATTCGGAGCTGCCCCCGCAGACGG                   CCTCCGAGGCTCCCAGTGAGGGGTCTAGGAGAAGCTCATCCGACCTCATCACCCTCCC                   AGCCACCACTCCCCCATGTCCCACCAAGAAGGAATGGGAAGGGCCAGCCACCTCGTAC                   ATGACATGCAGCGCCTACCAGAAGGTCCAGGACTCGGAGATCAGCTTCCCCGCGGGCG                   TGGAGGTGCAGGTGCTGGAGAAGCAGGAGAGCGGGTGGTGGTATGTGAGGTTTGGGGA                   GCTGGAGGGCTGGGCCCCTTCCCACTATTTGGTGCTGGATGAGAACGAGCAACCTGAC                   CCCTCTGGCAAAGAGCTGGACACAGTGCCCGCCAAGGGCAGGCAGAACGAAGGCAAAT                   CAGACAGCCTGGAGAAGATCGAGAGGCGCGTCCAAGCACTGAACACCGTCAACCAGAG                   CAAGAAGGCCACGCCCCCCATCCCCTCCAAACCTCCCGGGGGCTTCGGCAAGACCTCA                   GGCACTCCAGCGGTGAAGATGAGGAACGGAGTGCGGCAGGTGGCGGTCAGGCCCCAGT                   CGGTGTTTGTGTCCCCGCCACCCAAGGACAACAACCTGTCCTGCGCCCTGCGGAGGAA                   TGAGTCACTCACGGCCACTGATGGCCTCCGAGGCGTCCGACGGAACTCCTCCTTTAGC                   ACTGCTCGCTCCGCTGCCGCCGAGGCCAAGGGCCGCCTGGCCGAACGGGCTGCCAGCC                   AGGGTTCAGACTCACCCCTACTGCCCGCCCAGCGCAACAGCATACCCGTGTCCCCTGT                   GCGCCCCAAGCCCATCGAGAAGTCTCAGTTCATCCACAATAACCTCAAAGATGTGTAC                   GTCTCTATCGCAGACTACGAGGGGGATGAGGAGACAGCAGGCTTCCAGGAGGGGGTGT                   CCATGGAGGTTCTGGAGAGGAACCCTAATGGCTGGTGGTACTGCCAGATCCTGGATGG                   TGTGAAGCCCTTCAAAGGCTGGGTGCCTTCCAACTACCTTGAGAAAAAGAACTAG CAG                       AGGGCCTGGGCTCTTCCAGCCTCAGTGTGCCTCTCTGGCCGCCCACTGGATGAG                                       ORF Start: ATG at 61   ORF Stop: TAG at 3475           SEQ ID NO:60   1138 aa MW at 125800.4 kD                     NOV28a,   MLAYCVQDATVVDVEKRRNPSKHYVSTPQVYIINVTWSDSTSQTIYRRYSKFFDLQMQ               CG108861-01   LLDKFPIEGGQKDPKQRIIPFLPGKILFRRSHIRDVAVKRLKPIDEYCRALVRLPPHI               Protein Sequence   SQCDEVFRFFEARPEDVNPPKEDYGSSKRKSVWLSSWAESPKKDVTGADATAEPMILE                   QYVVVSNYKKQENSELSLQAGEVVDVIEKNESGWWFVSTSEEQGWVPATYLEAQNGTR                   DDSDINTSKTGEVSKRRKAHLRRLDRRWTLGGMVNRQHSREEKYVTVQPYTSQSKDEI                   GFEKGVTVEVIRKNLEGWWYIRYLGKEGWAPASYLKKAKDDLPTRKKNLAGPVEIIGN                   IMEISNLLNKKASGDKETPPAEGEGHEAPIAKKEISLPILCNASNGSAVGVPDRTVSR                   LAQGSPAVARIAPQRAQISSPNLRTRPPPRRESSLGFQLPKPPEPPSVEVEYYTIAEF                   QSCISDGISFRGGQKAEVIDKNSGGWWYVQIGEKEGWAPASYIDKRKKPNLSRRTSTL                   TRPKVPPPAPPSKPKEAEEGPTGASESQDSPRKLKYEEPEYDIPAFGFDSEPELSEEP                   VEDRASGERRPAQPHRPSPASSLQRARFKVGESSEDVALEEETIYENEGFRPYAEDTL                   SARGSSGDSDSPGSSSLSLTRKNSPKSGSPKSSSLLKLKAEKNAQAEMGKNHSSASFS                   SSITINTTCCSSSSSSSSSLSKTSGDLKPRSASDAGIRGTPKVRAKKDADANAGLTSC                   PRAKPSVRPKPFLNRAESQSQEKMDISTLRRQLRPTGQLRGGLKGSKSEDSELPPQTA                   SEAPSEGSRRSSSDLITLPATTPPCPTKKEWEGPATSYMTCSAYQKVQDSEISFPAGV                   EVQVLEKQESGWWYVRFGELEGWAPSHYLVLDENEQPDPSGKELDTVPAKGRQNEGKS                   DSLEKIERRVQALNTVNQSKKATPPIPSKPPGGFGKTSGTPAVKMRNGVRQVAVRPQS                   VFVSPPPKDNNLSCALRRNESLTATDGLRGVRRNSSFSTARSAAAEAKGRLAERAASQ                   GSDSPLLPAQRNSIPVSPVRPKPIEKSQFIHNNLKDVYVSIADYEGDEETAGFQEGVS                   MEVLERNPNGWWYCQILDGVKPFKGWVPSNYLEKKN                  
 
     [0442] Further analysis of the NOV28a protein yielded the following properties shown in Table 28B.  
               TABLE 28B                       Protein Sequence Properties NOV28a                                        PSort   0.9600 probability located in nucleus; 0.3000 probability       analysis:   located in microbody (peroxisome); 0.1000 probability           located in mitochondrial matrix space; 0.1000 probability           located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0443] A search of the NOV28a protein against the Genseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 28C.  
               TABLE 28C                          Geneseq Results for NOV28a                                         NOV28a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAU14174   Human novel protein #45 -  Homo     171 . . . 1138     968/968 (100%)   0.0             sapiens , 968 aa. [WO200155437-   1 . . . 968    968/968 (100%)           A2, 02-AUG-2001]       AAU68543   Human novel cytokine encoded by   6 . . . 223   146/218 (66%)   8e−83           cDNA 790CIP2D_4 #1 -  Homo     7 . . . 204   175/218 (79%)             sapiens , 215 aa. [WO200175093-           A1, 11-OCT-2001]       AAM79155   Human protein SEQ ID NO: 1817 -   1 . . . 138   133/138 (96%)   3e−72             Homo sapiens , 194 aa.   1 . . . 133   133/138 (96%)           [WO200157190-A2, 09-AUG-2001]       AAM80139   Human protein SEQ ID NO: 3785 -   1 . . . 138   132/138 (95%)   1e−71             Homo sapiens , 206 aa.   13 . . . 145    132/138 (95%)           [WO200157190-A2, 09-AUG-2001]       ABG15716   Novel human diagnostic protein   6 . . . 140   101/135 (74%)   8e−56           #15707 -  Homo sapiens , 142 aa.   13 . . . 142    119/135 (87%)           [WO200175067-A2, 11-OCT-2001]                  
 
     [0444] In a BLAST search of public sequence databases, the NOV28a protein was found to have homology to the proteins shown in the BLASTP data in Table 28D.  
               TABLE 28D                          Public BLASTP Results for NOV28a                                         NOV28a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9H462   BA416N2.2 (SIMILAR TO   108 . . . 1138   1031/1031 (100%)    0.0           MURINE FISH (AN SH3 AND    1 . . . 1031   1031/1031 (100%)            PX DOMAIN-CONTAINING           PROTEIN, AND SRC           SUBSTRATE)) -  Homo sapiens             (Human), 1031 aa (fragment).       O89032   FISH PROTEIN -  Mus musculus      1 . . . 1138   1032/1138 (90%)    0.0           (Mouse), 1124 aa.    1 . . . 1124   1062/1138 (92%)        O43302   KIAA0418 PROTEIN -  Homo     171 . . . 1138   940/968 (97%)   0.0             sapiens  (Human), 940 aa.    1 . . . 940   940/968 (97%)       Q9NTM6   BA541N10.2 (NOVEL PROTEIN    1 . . . 107   102/107 (95%)   5e−52           (ORTHOLOG OF MOUSE FISH    1 . . . 102   102/107 (95%)           PROTEIN)) -  Homo sapiens             (Human), 102 aa (fragment).       Q95MN0   NADPH OXIDASE P47-PHOX -    6 . . . 339   112/334 (33%)   3e−51             Oryctolagus cuniculus  (Rabbit),    6 . . . 294   176/334 (52%)           391 aa.                  
 
     [0445] PFam analysis predicts that the NOV28a protein contains the domains shown in the Table 28E.  
               TABLE 28E                          Domain Analysis of NOV28a                                 NOV28a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               PX    3 . . . 129   39/149 (26%)    2.4e−23               105/149 (70%)        SH3   174 . . . 228   18/58 (31%)   1.9e−11               43/58 (74%)       SH3   274 . . . 328   19/58 (33%)   3.9e−09               42/58 (72%)       SH3   456 . . . 510   14/58 (24%)   7.1e−05               36/58 (62%)       SH3   848 . . . 902   17/58 (29%)   2.5e−05               39/58 (67%)       SH3   1080 . . . 1137   20/61 (33%)   0.0002               46/61 (75%)                  
 
     Example 29  
     [0446] The NOV29 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 29A.  
               TABLE 29A                       NOV29 Sequence Analysis                                                SEQ ID NO:61   1441 bp                     NOV29a,     AAAG ATGTCTACTCTCCTGGAAAACATCTTTGCCATAATTAATCTTTTCAAGCAATAT               CG109523-01   TCAAAAAAAGATAAAAACACTGACACATTGAGTAAAAAAGAGCTGAAGGAACTTCTGG               DNA Sequence   AAAAGGAATTTCGGCAAATCCTGAAGAATCCAGATGACCCAGATATGGTTGATGTCTT                   CATGGATCACTTGGATATAGACCACAACAAGAAAATTGACTTCACTGAGTTTCTTCTG                   ATGGTATTCAAGTTGGCTCAAGCATATTATGAGTCTACCAGAAAAGAGAATTTACCGA                   TATCAGGACACAAGCACAGAAAGCACAGTCATCATGATAAACATGAAGATAATAAACA                   AAAGGGAATAAGGGAAGATCCAAGAGCCCAAGAGAAACAGGGGGGAAAAGGCATGAAT                   CTAGTTCTGAAAAAAAAGAAAGAAAAGGATATTCACCTACTCATAGAGAAGAAGAATA                   TGGAAAAAACCATCATAACTCAAGTAAAAAAGAGAAAAACAAGACTGAAAATACTAGA                   TTAGGAGACAATAGGAAGAGGCTAAGTGAAAGACTTGAAGAGAAAGAAGACAATGAAG                   AAGGAGTATATGATTATGAAAATACAGGAAGAATGACTCAAAAATGGATACAATCAGG                   CCATATTGCCACATATTACACAATCCAGGATGAAGCCTATGACACCACTGATAGTCTA                   TTAGAAGAAAACAAAATATATGAAAGATCAAGGTCATCTGATGGCAAATCATCATCTC                   AAGTGAACAGGTCAAGACATGAAAATACAAGCCAGGTACCATTGCAGGAGTCCAGGAC                   AAGAAAGCGTAGGGGATCCAGAGTTAGCCAGGACAGGGACAGCCAGGGACACTCAGAA                   GACTCCGAGAGGCACTCTGGGTCGGCTTCCAGAAACCATCATGGATCTGCGTGGGAGC                   AGTCAAGAGATGGCTCCAGACACCCCAGGTCCCATGATGAAGACAGAGCCAGTCATGG                   GCACTCTGCAGACAGCTCCAGACAATCAGGCACTCGTCACGCAGAGGAAACTTCCTCT                   CGTGGACAGACTGCATCATCCCATGAACAGGCAAGATCAAGTCCAGGAGAAAGACATG                   GATCCCACCACCAGCTCCAGTCAGCAGACAGCTCCAGACACTCAGCCACTGGGCGCGG                   GCAAGCTTCATCTGCAGTCAGCGATCGTGGACACCGGGGGTCTAGCGGTAGTCAGGCC                   AGTGACAGTGAGGGACATTCAGAAAACTCAGACACACAATCAGTGTCGGCCCACGGAA                   AGGCTGGGCTGAGACAGCAGAGCCACCAAGAGTCCACACGTGGCCGGTCAGCAGGAAC                   GGTCTGGACGTTCAGGGTCTTCCCTCTACCAGGTGAGCTCTCATGA ACA                                       ORF Start: ATG at 5   ORF Stop: TGA at 1436           SEQ ID NO:62   477 aa MW at 54535.2 kD                     NOV29a,   MSTLLENIFAIINLFKQYSKKDKNTDTLSKKELKELLEKEFRQILKNPDDPDMVDVFM               CG109523-01   DHLDIDHNKKIDFTEFLLMVFKLAQAYYESTRKENLPISGHKHRKHSHHDKHEDNKQE               Protein Sequence   ENRENRKRPSSLERRNNRKGNKGRSKSPRETGGKRHESSSEKKERKGYSPTHREEEYG                   KNHHNSSKKEKNKTENTRLGDNRKRLSERLEEKEDNEEGVYDYENTGRMTQKWIQSGH                   IATYYTIQDEAYDTTDSLLEENKIYERSRSSDGKSSSQVNRSRHENTSQVPLQESRTR                   KRRGSRVSQDRDSQGHSEDSERHSGSASRNHHGSAWEQSRDGSRHPRSHDEDRASHGH                   SADSSRQSGTRHAEETSSRGQTASSHEQARSSPGERHGSHHQLQSADSSRHSATGRGQ                   ASSAVSDRGHRGSSGSQASDSEGHSENSDTQSVSAHGKAGLRQQSHQESTRGRSAGTV                   WTFRVFPLPGELS                  
 
     [0447] Further analysis of the NOV29a protein yielded the following properties shown in Table 29B.  
               TABLE 29B                       Protein Sequence Properties NOV29a                                        PSort   0.5500 probability located in endoplasmic reticulum       analysis:   (membrane); 0.1900 probability located in lysosome (lumen);           0.1800 probability located in nucleus;           0.1000 probability located in endoplasmic           reticulum (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0448] A search of the NOV29a protein against the Genseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 29C.  
               TABLE 29C                          Geneseq Results for NOV29a                                         NOV29a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAY22956   Human filagrin sequence of clone   152 . . . 463   175/322 (54%)   5e−79           HB2650 -  Homo sapiens , 330 aa.    11 . . . 321   200/322 (61%)           [WO9928344-A2, 10-JUN-1999]       AAY22954   Human filagrin sequence of clone   152 . . . 463   174/322 (54%)   1e−78           HB2641 -  Homo sapiens , 330 aa.    11 . . . 321   199/322 (61%)           [WO9928344-A2, 10-JUN-1999]       AAY22957   Human filagrin sequence of clone   102 . . . 463   175/362 (48%)   4e−78           HB2648 -  Homo sapiens , 330 aa.    28 . . . 321   211/362 (57%)           [WO9928344-A2, 10-JUN-1999]       AAY22955   Human filagrin sequence of clone   152 . . . 463   173/322 (53%)   6e−78           HB2642 -  Homo sapiens , 330 aa.    11 . . . 321   199/322 (61%)           [WO9928344-A2, 10-JUN-1999]       AAM25257   Human protein sequence SEQ ID    1 . . . 206    80/210 (38%)   3e−31           NO: 772 -  Homo sapiens , 218 aa.    5 . . . 214   116/210 (55%)           [WO200153455-A2, 26-JUL-2001]                  
 
     [0449] In a BLAST search of public sequence databases, the NOV29a protein was found to have homology to the proteins shown in the BLASTP data in Table 29D.  
               TABLE 29D                          Public BLASTP Results for NOV29a                                         NOV29a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q01720   FILAGGRIN PRECURSOR   1 . . . 460   454/460 (98%)   0.0           (PROFILAGGRIN) -  Homo     1 . . . 458   456/460 (98%)             sapiens  (Human), 591 aa           (fragment).       Q9H4U2   DJ14N1.1.1 (PROFILAGGRIN 5′   1 . . . 460   454/460 (98%)   0.0           END) -  Homo sapiens  (Human),   1 . . . 458   456/460 (98%)           687 aa (fragment).       Q05331   FILAGGRIN (PROFILAGGRIN) -   1 . . . 462   434/462 (93%)   0.0             Homo sapiens  (Human), 1218 aa   1 . . . 460   443/462 (94%)           (fragment).       A48118   major epidermal calcium-binding   2 . . . 307   296/306 (96%)   e−174           protein profilaggrin - human, 306   1 . . . 306   301/306 (97%)           aa (fragment).       Q03838   FILAGGRIN (PROFILAGGRIN) -   223 . . . 460    227/238 (95%)   e−125             Homo sapiens  (Human), 465 aa   1 . . . 236   229/238 (95%)           (fragment).                  
 
     [0450] PFam analysis predicts that the NOV29a protein contains the domains shown in the Table 29E.  
               TABLE 29E                          Domain Analysis of NOV29a                                 NOV29a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               S_100    4 . . . 47   27/44 (61%)   2.6e−19               41/44 (93%)       efhand   53 . . . 81    9/29 (31%)   0.035               23/29 (79%)                  
 
     Example 30  
     [0451] The NOV30 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 30A.  
               TABLE 30A                       NOV30 Sequence Analysis                                                SEQ ID NO:63   1247 bp                     NOV30a,     CGGGAACCCCAACTGGAGTGGGTCCTCACTGTTCTCTTTTTCCTCTGGCAGCCTTGGA                 CG109649-01     GC ATGGCAAGTCCAGAGCACCCTGGGAGCCCTGGCTGCATGGGACCCATAACCCAGTG               DNA Sequence   CACGGCAAGGACCCAGCAGGAAGCACCAGCCACTGGCCCCGACCTCCCGCACCCAGGA                   CCTGACGGGCACTTAGACACACACAGTGGCCTGAGCTCCAACTCCAGCATGACCACGC                   GGGAGCTTCAGCAGTACTGGCAGAACCAGAAATGCCGCTGGAAGCACGTCAAACTGCT                   CTTTGAGATCGCTTCAGCTCGCATCGAGGAGAGAAAAGTCTCTAAGTTTGTGGTGTAC                   CAAATCATCGTCATCCAGACTGGGAGCTTTGACAACAACAAGGCCGTCCTGGAACGGC                   GCTATTCCGACTTCGCGAAGCTCCAGAAAGCGCTGCTGAAGACGTTCAGGGAGGAGAT                   CGAAGACGTGGAGTTTCCCAGGAAGCACCTGACTGGGAACTTCGCTGAGGAGATGATC                   TGTGAGCGTCGGCGCGCCCTGCAGGAGTACCTGGGCCTGCTCTACGCCATCCGCTGCG                   TGCGCCGCTCCCGGGAGTTCCTGGACTTCCTCACGCGGCCGGAGCTGCGCGAGGCTTT                   CGGCTGCCTGCGGGCCGGCCAGTACCCGCGCGCCCTGGAGCTGCTGCTGCGCGTGCTG                   CCGCTGCAGGAGAAGCTCACCGCCCACTGCCCTGCGGCCGCCGTCCCGGCCCTGTGCG                   CCGTGCTGCTGTGCCACCGCGACCTCGACCGCCCCGCCGAGGCCTTCGCGGCCGGAGA                   GAGGGCCCTGCAGCGCCTGCAGGCCCGGGAGGGCCATCGCTACTATGCGCCTCTGCTG                   GACGCCATGGTCCGCCTGGCCTACGCGCTGGGCAAGGACTTCGTGACTCTGCAGGAGA                   GGCTGGAGGAGAGCCAGCTCCGGAGGCCCACGCCCCGAGGCATCACCCTGAAGGAGCT                   CACTGTGCGAGAATACCTGCACTGA GCCGGCCTGGGACCCCGCAGGGACGCTGGAGAT                       TTGGGGTCACCATGGCTCACAGTGGGCTGTTTGGGGTTCTTTTTTTTTATTTTTCCTT                       TTCTTTTTTGTTATTTGAGACAGTCTTGCTCTGTCACCCAGACTGAAGTGCAGTGGCT                       CAATTATGTCTCACTGCAGCCTCAAACTCCTGGGCACAAGCAATCCTCCCACCTCAGC                       CTCCCAAGTAGCTGGGATTACAGGTGCAG                                       ORF Start: ATG at 61   ORF Stop: TGA at 1009           SEQ ID NO:64   316 aa MW at 36177.2 kD                     NOV30a,   MASPEHPGSPGCMGPITQCTARTQQEAPATGPDLPHPGPDGHLDTHSGLSSNSSMTTR               CG109649-01   ELQQYWQNQKCRWKHVKLLFEIASARIEERKVSKFVVYQIIVIQTGSFDNNKAVLERR               Protein Sequence   YSDFAKLQKALLKTFREEIEDVEFPRKHLTGNFAEEMICERRRALQEYLGLLYAIRCV                   RRSREFLDFLTRPELREAFGCLRAGQYPRALELLLRVLPLQEKLTAHCPAAAVPALCA                   VLLCHRDLDRPAEAFAAGERALQRLQAREGHRYYAPLLDAMVRLAYALGKDFVTLQER                   LEESQLRRPTPRGITLKELTVREYLH                  
 
     [0452] Further analysis of the NOV30a protein yielded the following properties shown in Table 30B.  
               TABLE 30B                       Protein Sequence Properties NOV30a                                        PSort   0.8500 probability located in endoplasmic reticulum       analysis:   (membrane); 0.4400 probability located in plasma membrane;           0.3000 probability located in microbody (peroxisome);           0.1000 probability located in mitochondrial           inner membrane       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0453] A search of the NOV30a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 30C.  
               TABLE 30C                          Geneseq Results for NOV30a                                         NOV30a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAG79225   Amino acid sequence of a human    1 . . . 316   316/316 (100%)   0.0           PSGL-1 binding protein -  Homo      1 . . . 316   316/316 (100%)             sapiens , 316 aa. [WO200173028-           A2, 04-OCT-2001]       AAG79120   Amino acid sequence of IBD1prox    1 . . . 316   316/316 (100%)   0.0           protein -  Homo sapiens , 334 aa.    19 . . . 334   316/316 (100%)           [FR2806739-A1, 28-SEP-2001]       AAB43067   Human ORFX ORF2831    7 . . . 95    85/89 (95%)   4e−46           polypeptide sequence SEQ ID    26 . . . 114    86/89 (96%)           NO: 5662 -  Homo sapiens , 148 aa.           [WO200058473-A2, 05-OCT-2000]       AAM89008   Human immune/haematopoietic    1 . . . 58    58/58 (100%)   1e−29           antigen SEQ ID NO: 16601 -   19 . . . 76    58/58 (100%)             Homo sapiens , 156 aa.           [WO200157182-A2, 09-AUG-2001]       ABG27894   Novel human diagnostic protein    1 . . . 44    44/44 (100%)   1e−21           #27885 -  Homo sapiens , 580 aa.   350 . . . 393    44/44 (100%)           [WO200175067-A2, 11-OCT-2001]                  
 
     [0454] In a BLAST search of public sequence datbases, the NOV30a protein was found to have homology to the proteins shown in the BLASTP data in Table 30D.  
               TABLE 30D                          Public BLASTP Results for NOV30a                                         NOV30a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               CAD10213   SEQUENCE 4 FROM PATENT   1 . . . 316    316/316 (100%)   0.0           WO0172822 -  Homo sapiens     19 . . . 334     316/316 (100%)           (Human), 334 aa (fragment).       CAD10211   SEQUENCE 1 FROM PATENT   1 . . . 316    316/316 (100%)   0.0           WO0173028 -  Homo sapiens     1 . . . 316    316/316 (100%)           (Human), 316 aa.       Q9D2Y5   Sorting nexin 20 -  Mus musculus     1 . . . 315   244/315 (77%)   e−138           (Mouse), 313 aa.   1 . . . 312   269/315 (84%)       Q969T3   Sorting nexin 21 -  Homo sapiens     37 . . . 315    103/281 (36%)   4e−38           (Human), 373 aa.   100 . . . 372     145/281 (50%)       Q8WY78   PP3993 -  Homo sapiens     138 . . . 315      69/180 (38%)   2e−21           (Human), 184aa.   4 . . . 183    94/180 (51%)                  
 
     [0455] PFam analysis predicts that the NOV30a protein contains the domains shown in the Table 30E.  
               TABLE 30E                          Domain Analysis of NOV30a                                         NOV30a   Identities/               Pfam   Match   Similarities   Expect           Domain   Region   for the Matched Region   Value                       PX   78 . . . 187   34/140 (24%)   3.1e−16                   82/140 (59%)                      
 
     Example 31  
     [0456] The NOV31 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3 1A.  
               TABLE 31A                       NOV31 Sequence Analysis                                                SEQ ID NO:65   867 bp                     NOV31a,     GGAACTCGGGCTAGCTAAGGAGGCCATTCTTG   ATG TTGCTTCTAGATCTCATGTCATC               CG110063-01   ACCGAGCCCTCAGCTGCTGGTGGCAGCTGCTCAGCAGACCCTTGGCATGGGAAAGAGA               DNA Sequence   CGGAGTCCACCCCAAGCCATCTGCCTTCACTTAGCTGGAGAGGTGCTGGCTGTGGCCC                   GGGGACTGAAGCCAGCTGTGCTCTATGATTGCAACTGTGCAGGGGCATCAGAGCTCCA                   GAGCTATCTGGAGGAGCTGAAGGGGCTTGGCTTCCTGACTTTTGGACTTCACATCCTT                   GAGATTGGAGAAAACAGCCTGATTGTCAGTCCTGAGCATGTATGTCAGCACTTGGAGC                   AGGTGCTGCTTGGTACCATAGCCTTTGTGGATGTTTCCAGCTGCCAGCGTCACCCTTC                   TGTCTGCTCCCTGGACCAGCTTCAGGACTTGAAGGCCCTCGTGGCTGAGATCATCACA                   CATTTGCAGGGGCTGCAGAGGGACTTATCTCTAGCAGTCTCCTACAGCAGGCTCCATT                   CCTCAGACTGGAATCTGTGTACTGTATTTGGGATCCTCCTGGGCTATCCTGTTCCCTA                   TACCTTTCACCTGAACCAGGGAGATGACAACTGCTTAGCTCTGACTCCACTACGAGTA                   TTCACTGCCCGGATCTCATGGTTGCTAGGTCAACCCCCAATCCTGCTCTATTCTTTTA                   GTGTCCCACAGAGTTTGTTCCCAGGCCTGAGGGACATTCTAAACACCTGGGAGAAGGA                   CCTCAGAACCCGATTTAGGACTCAGAATGACTTTGCTGATCTCAGCATCTCCTCTGAG                   ATAGTCACACTGCCGGCTGTGGCCCTC TGA   CTTTAACTCTCCTCCCATATAGAAG                                       ORF Start: ATG at 33   ORF Stop: TGA at 840           SEQ ID NO:66   269 aa MW at 29560.8 kD                     NOV31a,   MLLLDLMSSPSPQLLVAAAQQTLGMGKRRSPPQAICLHLAGEVLAVARGLKPAVLYDC               CG110063-01   NCAGASELQSYLEELKGLGFLTFGLHILEIGENSLIVSPEHVCQHLEQVLLGTIAFVD               Protein Sequence   VSSCQRHPSVCSLDQLQDLKALVAEIITHLQGLQRDLSLAVSYSRLHSSDWNLCTVFG                   ILLGYPVPYTFHLNQGDDNCLALTPLRVFTARISWLLGQPPILLYSFSVPESLFPGLR                   DILNTWEKDLRTRFRTQNDFADLSISSEIVTLPAVAL                                     SEQ ID NO:67   856 bp                     NOV31b,     CTAGCTAAGGAGGCCATTCTTG   ATG TTGCTTCTAGATCTCATGTCATCACCGAGCCCT               CG110063-02   CAGCTGCTGGTGGCAGCTGCTCAGCAGACCCTTGGCATGGGAAAGAGACGGAGTCCAC               DAN Sequence   CCCAAGCCATCTGCCTTCACTTAGCTGGAGAGGTGCTGGCTGTGGCCCGGGGACTGAA                   GCCAGCTGTGCTCTATGATTGCAACTGTGCAGGGGCATCAGAGCTCCAGAGCTATCTG                   GAGGAGCTGAAGGGGCTTGGCTTCCTGACTTTTGGACTTCACATCCTTGAGATTGGAG                   AAAACAGCCTGATTGTCAGTCCTGAGCATGTATGTCAGCACTTGGAGCAGGTGCTGCT                   TGGTACCATAGCCTTTGTGGATGTTTCCAGCTGCCAGCGTCACCCTTCTGTCTGCTCC                   CTGGACCAGCTTCAGGACTTGAAGGCCCTCGTGGCTGAGATCATCACACATTTGCAGG                   GGCTGCAGAGGGACTTATCTCTAGCAGTCTCCTACAGCAGGCTCCATTCCTCAGACTG                   GAATCTGTGTACTGTATTTGGGATCCTCCTGGGCTATCCTGTTCCCTATACCTTTCAC                   CTGAACCAGGGAGATGACAACTGCTTAGCTCTGACTCCACTACGAGTATTCACTGCCC                   GGATCTCATGGTTGCTAGGTCAACCCCCAATCCTGCTCTATTCTTTTAGTGTCCCAGA                   GAGTTTGTTCCCAGGCCTGAGGGACATTCTAAACACCTGGGAGAAGGACCTCAGAACC                   CGATTTAGGACTCAGAATGACTTTGCTGATCTCAGCATCTCCTCTGAGATAGTCACAC                   TGCCGGCTGTGGCCCTC TGA   CTTTAACTCTCCTCCCATATAGAA                                       ORF Start: ATG at 23   ORF Stop: TGA at 830           SEQ ID NO:68   269 aa MW at 29560.8 kD                     NOV31b.   MLLLDLMSSPSPQLLVAAAQQTLGMGKRRSPPQAICLHLAGEVLAVARGLKPAVLYDC               CG110063-02   NCAGASELQSYLEELKGLGFLTFGLHILEIGENSLIVSPEHVCQHLEQVLLGTIAFVD               Protein Sequence   VSSCQRHPSVCSLDQLQDLKALVAEIITHLQGLQRDLSLAVSYSRLHSSDWNLCTVFG                   ILLGYPVPYTFHLNQGDDNCLALTPLRVFTARISWLLGQPPILLYSFSVPESLFPGLR                   DILNTWEKDLRTRFRTQNDFADLSISSEIVTLPAVAL                  
 
     [0457] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 31B.  
               TABLE 31B                          Comparison of NOV31a against NOV31b.                         Protein   NOV31a Residues/   Identities/       Sequence   Match Residues   Similarities for the Matched Region               NOV31b   16 . . . 269   254/254 (100%)           16 . . . 269   254/254 (100%)                  
 
     [0458] Further analysis of the NOV31a protein yielded the following properties shown in Table 31C.  
               TABLE 31C                       Protein Sequence Properties NOV31a                                        PSort   0.3600 probability located in mitochondrial matrix space; 0.3000 probability       analysis:   located in microbody (peroxisome); 0.2167 probability located in lysosome           (lumen); 0.1000 probability located in nucleus       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0459] A search of the NOV31a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 31D.  
               TABLE 31D                          Geneseq Results for NOV31a                                         NOV31a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAG75024   Human colon cancer antigen     1 . . . 107   107/107 (100%)    1e−55           protein SEQ ID NO:5788 -  Homo       7 . . . 113   107/107 (100%)              sapiens , 113 aa. [WO200122920-           A2, 05 Apr. 2001]       ABG07312   Novel human diagnostic protein    88 . . . 160   28/76 (36%)   5.6           #7303 -  Homo sapiens , 1132 aa.   131 . . . 205   34/76 (43%)           [WO200175067-A2, 11 Oct. 2001]       ABG07312   Novel human diagnostic protein    88 . . . 160   28/76 (36%)   5.6           #7303 -  Homo sapiens , 1132 aa.   131 . . . 205   34/76 (43%)           [WO200175067-A2, 11 Oct. 2001]                  
 
     [0460] In a BLAST search of public sequence datbases, the NOV31a protein was found to have homology to the proteins shown in the BLASTP data in Table 31E.  
               TABLE 31E                          Public BLASTP Results for NOV31a                                         NOV31a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96LT6   CDNA FLJ25078 FIS, CLONE   1 . . . 269   269/269 (100%)   e−153           CBL06954 -  Homo sapiens     1 . . . 269   269/269 (100%)           (Human), 269 aa.       Q9DAE8   ADULT MALE TESTIS CDNA,   7 . . . 269   208/263 (79%)    e−118           RIKEN FULL-LENGTH   1 . . . 263   232/263 (88%)            ENRICHED LIBRARY,           CLONE: 1700012B08, FULL           INSERT SEQUENCE -  Mus               musculus  (Mouse), 263 aa.                  
 
     [0461] PFam analysis predicts that the NOV31a protein contains the domains shown in the Table 31F.  
               TABLE 31F                       Domain Analysis of NOV31a                                                        Pfam   NOV31a   Identities/   Expect           Domain   Match   Similarities   Value               Region   for the Matched Region                      
 
     Example 32  
     [0462] The NOV32 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 32A.  
               TABLE 32A                       NOV32 Sequence Analysis                                                SEQ ID NO:69   684 bp                     NOV32a     CCCGCTCCGGCCGGGACG   ATG GTGAAGTATTTCCTGGGCCAGAGCGTGCAACGGAGCT               CG110151-01   CCTGGGACCAAGTGTTCGCCGCCTTCTGGCAGCGGTACCCGAATCCCTATAGCAAACA               DNA Sequence   TGTCTTGACGGAAGACGTAGTACACCGGGAGGTAACCCCTGACCAGAAACTGCTGTCC                   GGGCGACTCCTGACCAAGACCAACAGGACGCCCTGCTGGGCCGAGCGACTGTTTCCTG                   CCAATGTTGATCACTCGGTGTACATCCTGGAGGACTCTATTGTGGACCCACAGAATCA                   GACCATGACCACCTTCACCTGGAACATCAACCATGCCCGGCTGATGGTGGTGGAGGAA                   CGATGTGTTTACTGTGTGAACTCTGACAACAGTGGCCGGACCGAAATCCGCCGGGAAG                   CCTGGGTCTCCTCTAGCTTATTTGGTGTCTCCAGAGCTGTCCAGGAATTTGGTCTTGC                   CTGGTTCAAAAGCAATGTGACCAAGACTATGAAGGGTTTTGAATATATCTTGGCAAAG                   CTGCAAGGCGAGGCCCCTTCCAAAACACTTGTTGAGACAGCCAAGGAAGCCAAGGAGA                   AGGCAAAGGAGACAGCACTGGCAGCTACAGAGAAGGCCAAGGACCTCGCCAGCAAGGC                   AGCCACCAAGAAGCAGCAGCAGCAGCAACAGTTTGTG TAG   CCAGCC                                       ORF Start: ATG at 19   ORF Stop: TAG at 676           SEQ ID NO:70   219 aa MW at 25057.3 kD                     NOV32a,   MVKYFLGQSVQRSSWDQVFAAFWQRYPNPYSKHVLTEDVVHREVTPDQKLLSGRLLTK               CG110151-01   TNRTPCWAERLFPANVDHSVYILEDSIVDPQNQTMTTFTWNINHARLMVVEERCVYCV               Protein Sequence   NSDNSGRTEIRREAWVSSSLFGVSRAVQEFGLAWFKSNVTKTMKGFEYILAKLQGEAP                   SKTLVETAKEAKEKAKETALAATEKAKDLASKAATKKQQQQQQFV                  
 
     [0463] Further analysis of the NOV32a protein yielded the following properties shown in Table 32B.  
               TABLE 32B                       Protein Sequence Properties NOV32a                                        PSort   0.5714 probability located in microbody (peroxisome); 0.3600 probability       analysis:   located in mitochondrial matrix space; 0.1000 probability located in lysosome           (lumen); 0.0000 probability located in endoplasmic reticulum (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0464] A search of the NOV32a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 32C.  
               TABLE 32C                          Geneseq Results for NOV32a                                         NOV32a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAW61538   Human LEA-motif developmental   1 . . . 219   210/219 (95%)   e−117           protein -  Homo sapiens , 219 aa.   1 . . . 219   212/219 (95%)           [WO9835041-A1, 13 Aug. 1998]       ABG09766   Novel human diagnostic protein   1 . . . 214   144/214 (67%)   3e−69           #9757 -  Homo sapiens , 167 aa.   1 . . . 167   152/214 (70%)           [WO200175067-A2, 11 Oct. 2001]       ABG09766   Novel human diagnostic protein   1 . . . 214   144/214 (67%)   3e−69           #9757 -  Homo sapiens , 167 aa.   1 . . . 167   152/214 (70%)           [WO200175067-A2, 11 Oct. 2001]       ABB12426   Human bone marrow expressed   26 . . . 101     63/77 (81%)   5e−30           protein SEQ ID NO: 265 -  Homo     19 . . . 95      66/77 (84%)             sapiens , 99 aa. [WO200174836-           A1, 11 Oct. 2001]       ABB59225     Drosophila melanogaster     18 . . . 106     48/89 (53%)   7e−17           polypeptide SEQ ID NO 4467 -   3 . . . 87     58/89 (64%)             Drosophila melanogaster , 171 aa.           [WO200171042-A2, 27 Sep. 2001]                  
 
     [0465] In a BLAST search of public sequence datbases, the NOV32a protein was found to have homology to the proteins shown in the BLASTP data in Table 32D.  
               TABLE 32D                          Public BLASTP Results for NOV32a                                         NOV32a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9Y255   PX19 (SBBI12) (PX19-LIKE   1 . . . 219   210/219 (95%)   e−117           PROTEIN) -  Homo sapiens     1 . . . 219   212/219 (95%)           (Human), 219 aa.       Q9UJS9   PRELI -  Homo sapiens  (Human),   1 . . . 219   209/219 (95%)   e−116           219 aa.   1 . . . 219   211/219 (95%)       AAH25859   SIMILAR TO PX19-LIKE   1 . . . 215   204/215 (94%)   e−114           PROTEIN -  Mus musculus     1 . . . 215   208/215 (95%)           (Mouse), 217aa.       Q9UI13   PX19 PROTEIN -  Homo sapiens     1 . . . 219   198/219 (90%)   e−108           (Human), 208 aa.   1 . . . 208   200/219 (90%)       Q90673   PX19 -  Gallus gallus  (Chicken),   1 . . . 213   175/213 (82%)   2e−97           215 aa.   1 . . . 213   189/213 (88%)                  
 
     [0466] PFam analysis predicts that the NOV32a protein contains the domains shown in the Table 32E.  
               TABLE 32E                       Domain Analysis of NOV32a                                                Pfam Domain   NOV32a   Identities/   Expect Value           Match Region   Similarities               for the               Matched Region                  
 
     Example 33  
     [0467] The NOV33 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 33A.  
               TABLE 33A                       NOV33 Sequence Analysis                                                SEQ ID NO:71   932 bp                     NOV33a,     GTCAAA   ATG CAGATCTTCGTGAAGACCCTGACTGGCAAGACCATCACCCTTGAAGTGG               CG110340-01   AGCCCAGTGACACCATCGAAAATGTGAAGGCCAATATCCAGGATAAGGAAGGCATCCT               DNA Sequence   CCCCGACCAGCAGAGGCTCATCTTTGCAGGCATGCAGCTAGAAGATGGCTGTACTCTT                   TCTGACTACAACATCCAGAAAGAGTTGACCCTGTACCTGGTCCAGCGTCTGAGATGTG                   GCATGCAGATCTTCGTGAAGACCCTGACTGGCAAGACCATCACCCTTGAAGTGGAGCC                   CACTGACACCATCGAAAATGTGAAGGCCAATATCCAGGATAAGGAAGGCATCCTCCCC                   GACCAGCAGAGGCTCATCTTTGCAGGCATGCAGCTAGAAGATGGCTGTACTCTTTCTG                   ACTACAACATCCAGAAAGAGTTGACCCTGTACCTGGTCCAGCGTCTGAGATGTGGCAT                   GCAGATCTTCGTGAAGACCCTGACTGGCAAGACCATCACCCTTGAAGTGGAGCCCAGT                   GACACCATCGAAAATGTGAAGGCCAATATCCAGGATAAGGAAGGCATCCTCCCCGACC                   AGCAGAGGCTCATCTTTGCAGGCATGCAGCTAGAAGATGGCTGTACTCTTTCTGACTA                   CAACATCCAGAAAGAGTTGACCCTGTACCTGGTCCAGCGTCTGAGATGTGGCATGCAG                   ATCTTCGTGAAGACCCTGACTGGCAAGACCATCACCCTTGAAGTGGAGCCCAGTGACA                   CCATCGAAAATGTGAAGGCCAATATCCAGGATAAGGAAGCCATCCTCCCCGACCAGCA                   GAGGCTCATCTTTGCAGGCATGCAGCTAGAAGATGGCTGTACTCTTTCTGACTACAAC                   ATCCAGAAAGAGTTGACCCTGTACCTGGTCCAGCGTCTGAGATGTGGCTGT TAG   TTCT                       TCAG                                       ORF Start: ATG at 7   ORF Stop: TAG at 922           SEQ ID NO:72   305 aa MW at 34568.6 kD                     NOV 33a,   MQIFVKTLTGKTITLEVEPSDTIENVKANIQDKEGILPDQQRLIFAGMQLEDGCTLSD               CG110340-01   YNIQKELTLYLVQRLRCGMQIFVKTLTGKTITLEVEPSDTIENVKANIQDKEGILPDQ               Protein Sequence   QRLIFAGMQLEDGCTLSDYNIQKELTLYLVQRLRCGMQIFVKTLTGKTITLEVEPSDT                   IENVKANIQDKEGILPDQQRLIFAGMQLEDGCTLSDYNIQKELTLYLVQRLRCGMQIF                   VKTLTGKTITLEVEPSDTIENVKANIQDKEGILPDQQRLIFAGMQLEDGCTLSDYNIQ                   KELTLYLVQRLRCGC                  
 
     [0468] Further analysis of the NOV33a protein yielded the following properties shown in Table 33B.  
               TABLE 33B                       Protein Sequence Properties NOV33a                                                PSort   0.6500 probability located in cytoplasm;           analysis:   0.1000 probability located in               mitochondrial matrix space; 0.1000               probability located in               lysosome (lumen);               0.0000 probability located in               endoplasmic reticulum (membrane)           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0469] A search of the NOV33a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 33C.  
               TABLE 33C                          Geneseq Results for NOV33a                                         NOV33a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               ABB67303     Drosophila melanogaster      1 . . . 304   272/304 (89%)   e−144           polypeptide SEQ ID NO: 28701 -   153 . . . 456   276/304 (90%)             Drosophila melanogaster , 719 aa.           [WO200171042-A2, 27-SEP-2001]       ABB65843     Drosophila melanogaster      1 . . . 304   272/304 (89%)   e−144           polypeptide SEQ ID NO: 24321 -   153 . . . 456   276/304 (90%)             Drosophila melanogaster , 719 aa.           [WO200171042-A2, 27-SEP-2001]       AAB58753   Breast and ovarian cancer    1 . . . 304   272/304 (89%)   e−144           associated antigen protein sequence    31 . . . 334   276/304 (90%)           SEQ ID 461 -  Homo sapiens , 390           aa [WO200055173-A1, 21-SEP-2000]       AAW14848   Poly-Ubiquitin - Synthetic, 685 aa.    1 . . . 304   272/304 (89%)   e−144           [JP09037779-A, FEB-10-1997]   381 . . . 684   276/304 (90%)       AAW14134   Human poly-ubiquitin protein -    1 . . . 304   272/304 (89%)   e−144             Homo sapiens , 685 aa.   381 . . . 684   276/304 (90%)           [JP09000263-A, 07-JAN-1997]                  
 
     [0470] In a BLAST search of public sequence datbases, the NOV33a protein was found to have homology to the proteins shown in the BLASTP data in Table 33D.  
               TABLE 33D                          Public BLASTP Results for NOV33a                                         NOV33a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               O46543   POLYUBIQUITIN -  Ovis aries      1 . . . 305   272/305 (89%)   e−144           (Sheep), 305 aa.    1 . . . 305   277/305 (90%)       S29853   polyubiquitin 4 - bovine, 305    1 . . . 305   272/305 (89%)   e−144           aa.    1 . . . 305   276/305 (90%)       Q9ET23   POLYUBIQUITIN C -  Mus      1 . . . 304   272/304 (89%)   e−144             musculus  (Mouse), 886 aa.   381 . . . 684   276/304 (90%)       Q9ET24   POLYUBIQUITIN C -  Mus      1 . . . 304   272/304 (89%)   e−144             musculus  (Mouse), 734 aa.   229 . . . 532   276/304 (90%)       S21083   polyubiquitin 5 - Chinese    1 . . . 304   272/304 (89%)   e−144           hamster, 381 aa.    77 . . . 380   276/304 (90%)                  
 
     [0471] PFam analysis predicts that the NOV33a protein contains the domains shown in the Table 33E.  
               TABLE 33E                          Domain Analysis of NOV33a                                     Identities/                   Similarities       Pfam Domain   NOV33a    for the    Expect Value           Match Region   Matched Region               ubiquitin    1 . . . 74   51/83 (61%)   2.5e−36               70/83 (84%)       ubiquitin    77 . . . 150   51/83 (61%)   2.5e−36               70/83 (84%)       ubiquitin   153 . . . 226   51/83 (61%)   2.5e−36               70/83 (84%)       ubiquitin   229 . . . 302   51/83 (61%)   2.5e−36               70/83 (84%)                  
 
     Example 34  
     [0472] The NOV34 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 34A.  
               TABLE 34A                       NOV34 Sequence Analysis                                                SEQ ID NO:73   2955 bp                     NOV34a,     TCGTGGTAGGGACTCTCCACCTACAATCACAATACCAGTAAATATAAATCATGCTGCT                 CG139264-01     AGTGGTTCCTTCAGAGAATCTGTGGACGCTCAAGAGGAAATCAGGAAAGTGGACGAAG                 DNA Sequence     AGAGCTACTTATGTTCATAAAGATGGACTAAATTCCACTGATCACATGGTGCCCGACA                       CTGAAAGTTATGATGCAGTTGAAATCATCCGCAAGGTTGCAGTGCCTCCTCGCCTGTC                       AGAGCACACACAGAGATATGAAGCGGCCAACCGAACTGTTCAAATGGCTGAAAATTTC                       GTGAATGACCCTGAAAATCAAATAAACAGATGGTTCAGGGAATTTGAGCATGGCCCAG                       TTTCTGAAGCAAAGTCAAATAGAAGAGTTTATGCAAAGGGAGAAACAAACCATAACAT                       ACAACAAGAAAGTCGTACATTTGTAAGGAGGAATTTGGATTAACATCTTTAGGAAACA                       CGAGTTTTACAGACTTTTCTTGCAAACATCCTAGAGAACTGCGAGAAAAGATTCCTGT                       TAAGCAGCCCAGGATCTGCTCTGAAACCAGGTCTCTAAGTGAACATTTCTCAGGCATG                       GATGCATTTGAGAGTCAAATTGTTGAGTCGAAGATGAAAACCTCTTCATCACATAGCT                       CAGAAGCTGGCAAATCTGGCTGTGACTTCAAGCATGCCCCACCAACCTATGAGGATGT                       CATTGCTGGACATATTTTAGATATCTCTGATTCACCTAAAGAAGTAAGAAAAAATTTT                       CAAAAGACGTGGCAAGAGAGTGGAAGAGTTTTTAAAGGCCTGGGATATGCAACCGCAG                       ATGCTTCTGCAACTGAGATGAGAACCACCTTCCAAGAGGAATCTGCATTTATAAGTGA                       AGCTGCTGCTCCAAGACAAGGAAATATGTATACTTGGTCAAAAGACAGTTTATCCAAT                       GGAGTGCCTAGTGGCAGACAAGCAGAATTTTCATAAGTCCTGCTTCCGATGCCACCAT                       TGCAACAGTAAACTAAGTTTGGGGAAATTATGCATCACTTCATGGACAAATATACTGT                       AAACCTCACTTTAAACAACTTTTCAAATCCAAAGGAAATTATGATGAAGGTTTTGGAC                       ATAAGCAGCATAAAGATAGATGGAACTGCAAAAACCAAAGCAGATCAGTGGACTTTAT                       TCCTAATGAAGAACCAAAT   ATG TGTAAAAATATTGCAGAAAACACCCTTGTACCTGGA                   GATCGTAATGAACATTTAGATGCTGGTAACAGTGAAGGGCAAAGGAATGATTTGAGAA                   AATTAGGGGAAAGGGGAAAATTAAAAGTCATTTGGCCTCCTTCCAAGGAGATCCCTAA                   GAAAACCTTACCCTTTGAGGAAGAGCTCAAAATGAGTAAACCTAAGTGGCCACCTGAA                   ATGACAACCCTGCTATCCCCTGAATTTAAAAGTGAATCTCTGCTAGAAGATGTTAGAA                   CTCCAGAAAATAAAGGACAAAGACAAGATCACTTTCCATTTTTGCAGCCTTATCTACA                   GTCCACCCATGTTTGTCAGAAAGAGGATGTTATAGGAATCAAAGAAATGAAAATGCCT                   GAAGGAAGAAAAGATGAAAAGAAGGAAGGAAGGAAGAATGTGCAAGATAGGCCGAGTG                   AAGCTGAAGACACAAAGAGTAACAGGAAAAGTGCTATGGATCTTAATGACAACAATAA                   TGTGATTGTGCAGAGTGCTGAAAAGGAGAAAAATGAAAAAACTAACCAAACTAATGGT                   GCAGAAGTTTTACAGGTTACTAACACTGATGATGAGATGATGCCAGAAAATCATAAAG                   AAAATTTGAATAAGAATAATAATAACAATTATGTAGCAGTCTCATATCTGAATAATTG                   CAGGCAGAAGACATCTATTTTAGAATTTCTTGATCTATTACCCTTGTCGAGTGAAGCA                   AATGACACTGCAAATGAATATGAAATTGAGAAGTTAGAAAATACATCTAGAATCTCAG                   AGTTACTTGGTATATTTGAATCTGAAAAGACTTATTCGAGGAATGTACTAGCAATGGC                   TCTGAAGAAACAGACTGACAGAGCAGCTGCTGGCAGTCCTGTGCAGCCTGCTCCAAAA                   CCAAGCCTCAGCAGAGGCCTTATGGTAAAGGGGGGAAGTTCAATCATCTCTCCTGATA                   CAAATCTCTTAAACATTAAAGGAAGCCATTCAAAGAGCAAAAATTTACACTTTTTCTT                   TTCTAACACCGTGAAAATCACTGCATTTTCCAAGAAAAATGAGAACATTTTCAATTGT                   GATTTAATAGATTCTGTAGATCAAATTAAAAATATGCCATGCTTGGATTTAAGGGAAT                   TGGAAAGGATGTTAAACCTTGGCATGTTGAAACAACAGAAGCTGCCCGCAATAATGAA                   AACACAGGTTTTGATGCTC TGA   GCCATGAATGTACAGCTAAGCCTTTGTTTCCCAGAG                       TGGAGGTGCAGTCAGAACAACTCACGGTGGAAGAGCAGATTAAAAGAAACAGGTGCTA                       CAGTGACACTGAGTAAAATATCTATGGCCACTGACAGTCCACACTTAGGCACTGAGAG                       ATATTGATGTTCTGAAATAAGATTTTATGAATTTGGATACCCTTTTGAGGAACTTGAT                       GTAAACATGGTGTTCAGAAATCTCGTGTCTATCTCAATGGGATATTTCTTGTATTACA                       CCTTGTCATTTTTTTCACAATTTATTTACATCTACTTTTGTTTGAACTGGAATGAAGA                       GATGAAACACTATGGATATGTTTTCCATTCAAATGGCACTTTAGCATATTGTTCTGTT                       TTCCTGTAAAACATCATGGGTGTGATTTTTATACTGCTGCTGCTTGTCACAATTATTA                       TAACTTCTCTGTAATTTCCTCTGAAATAAAATTGAATCACCTGAGGTGCCAAACCAAA                       AAAAAAATTCTATAACTTTTTTGATATAATACTGTCATTCTAAGTACATATGACT                                       ORF Start: ATG at 1180   ORF Stop: TGA at 2398           SEQ ID NO:74   406 aa MW at 46085.9 kD                     NOV34a,   MCKNIAENTLVPGDRNEHLDAGNSEGQRNDLRKLGERGKLKVIWPPSKEIPKKTLPFE               CG139264-01   EELKMSKPKWPPEMTTLLSPEFKSESLLEDVRTPENKGQRQDHFPFLQPYLQSTHVCQ               Protein Sequence   KEDVIGIKEMKMPEGRKDEKKEGRKNVQDRPSEAEDTKSNRKSAMDLNDNNNVIVQSA                   EKEKNEKTNQTNGAEVLQVTNTDDEMMPENHKENLNKNNNNNYVAVSYLNNCRQKTSI                   LEFLDLLPLSSEANDTANEYEIEKLENTSRISELLGIFESEKTYSRNVLAMALKKQTD                   RAAAGSPVQPAPKPSLSRGLMVKGGSSIISPDTNLLNIKGSHSKSKNLHFFFSNTVKI                   TAFSKKNENIFNCDLIDSVDQIKNMPCLDLRELERMLNLGMLKQQKLPAIMKTQVLML                  
 
     [0473] Further analysis of the NOV34a protein yielded the following properties shown in Table 34B.  
               TABLE 34B                       Protein Sequence Properties NOV34a                                                PSort   0.6500 probability located in cytoplasm;           analysis:   0.1000 probability located in               mitochondrial matrix space; 0.1000               probability located in lysosome               (lumen);               0.0000 probability located in               endoplasmic reticulum (membrane)           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0474] A search of the NOV34a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 34C.  
               TABLE 34C                          Geneseq Results for NOV34a                                         NOV34a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               AAE16626   Human 41441 protein encoded by    1 . . . 380   380/380 (100%)   0.0           EST clone AW755252 DNA -   105 . . . 484   380/380 (100%)             Homo sapiens , 547 aa.           [WO200192567-A2, 06-DEC-2001]       AAU20632   Human secreted protein, Seq ID    1 . . . 380   379/380 (99%)   0.0           No: 624 -  Homo sapiens , 547 aa.   105 . . . 484   379/380 (99%)           [WO200155326-A2, 02-AUG-2001]       AAU20575   Human secreted protein, Seq ID    1 . . . 380   379/380 (99%)   0.0           No: 567 -  Homo sapiens , 547 aa.   105 . . . 484   379/380 (99%)           [WO200155326-A2, 02-AUG-2001]       ABG04347   Novel human diagnostic protein    1 . . . 65    65/65 (100%)   5e−32           #4338 -  Homo sapiens , 171 aa.   107 . . . 171    65/65 (100%)           [WO200175067-A2, 11-OCT-2001]       ABG04347   Novel human diagnostic protein    1 . . . 65    65/65 (100%)   5e−32           #4338 -  Homo sapiens , 171 aa.   107 . . . 171    65/65 (100%)           [WO200175067-A2, 11-OCT-2001]                  
 
     [0475] In a BLAST search of public sequence datbases, the NOV34a protein was found to have homology to the proteins shown in the BLASTP data in Table 34D.  
               TABLE 34D                          Public BLASTP Results for NOV34a                                         NOV34a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9UHB6   Epithelial protein lost in    23 . . . 182    48/183 (26%)   3e−08           neoplasm -  Homo sapiens     513 . . . 692    83/183 (45%)           (Human), 759 aa.       AAM08756   HYPOTHETICAL 83.2 KDA    16 . . . 336    74/353 (20%)   4e−05           PROTEIN -  Dictyostelium     336 . . . 670   137/353 (37%)             discoideum  (Slime mold), 734 aa.       O96245   MTN3/RAG1IP-LIKE PROTEIN -   106 . . . 234    34/132 (25%)   3e−04             Plasmodium falciparum , 686 aa.   117 . . . 248    59/132 (43%)       Q9ERGO   Epithelial protein lost in    23 . . . 71    22/49 (44%)   3e−04           neoplasm (mEPLIN) -  Mus     511 . . . 557    30/49 (60%)             musculus  (Mouse), 753 aa.       P90523   PUTATIVE TRANSCRIPTION   123 . . . 349    46/228 (20%)   6e−04           FACTOR -  Dictyostelium      12 . . . 229    83/228 (36%)             discoideum  (Slime mold), 872 aa.                  
 
     [0476] PFam analysis predicts that the NOV34a protein contains the domains shown in the Table 34E.  
               TABLE 34E                       Domain Analysis of NOV34a                                                Pfam Domain   NOV34a   Identities/   Expect Value           Match Region   Similarities               for the               Matched Region                  
 
     Example 35  
     [0477] The NOV35 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 35A.  
               TABLE 35A                       NOV35 Sequence Analysis                                                SEQ ID NO:75   1826 bp                     NOV35a,     CGGCCGCGTCGACGGAAGGAACCTGACGACTTAGCAGGGTATCACTGGACAGGCC   ATG                 CG148240-01   GCTCCACGGTCCCGGCGACGAAGGCACAAGAAACCTCCCTCATCAGTGGCTCCCATCA               DNA Sequence   TCATGGCCCCAACCACAATTGTGACCCCTGTGCCTCTGACCCCCTCAAAACCTGGCCC                   TAGCATTGACACACTTGGCTTCTTCTCCTTGGATGATAATGTTCCTGGCCTATCGCAG                   CTGATCCTTCAAAAGCTGAACATGAAAAGCTATGAAGAATATAAGTTGGTGGTAGATG                   GGGGTACCCCCGTATCAGGCTTTGGATTTCGATGTCCTCAAGAAATGTTCCAGAGGAT                   GGAAGACACATTTCGATTCTGTGCTCACTGTAGAGCACTCCCTAGTGGGCTTTCAGAC                   TCCAAGGTTCTCCGGCACTGTAAGAGGTGCAGAAATGTCTATTACTGTGGTCCAGAGT                   GCCAGAAGTCAGACTGGCCCGCACACAGGAGGGTTTGTCAAGAGCTTCGTCTTGTGGC                   TGTGGACCGTCTCATGGAATGGCTTCTGGTCACAGGTGATTTTGTTCTACCCTCAGGA                   CCTTGGCCATGGCCACCTGAAGCTGTACAGGACTGGGACTCCTGGTTTTCTATGAAGG                   GGTTACACCTAGATGCTACATTGGATGCTGTGCTAGTTAGTCATGCTGTGACCACCTT                   ATGGGCCAGTGTAGGACGGCCAAGGCCAGACCCGGATGTCCTGCAGGGATCTTTGAAG                   CGGCTGCTGACAGATGTCCTGTCACGGCCCTTGACTCTAGGCCTAGGACTTAGGGCCT                   TGGGGATAGATGTTAGGAGGACTGGGGGAAGCACAGTGCATGTGGTTGGTGCTTCCCA                   TGTGGAGACATTTCTTACTCGCCCAGGGGACTATGATGAGCTTGGTTACATGTTTCCT                   GGGCACCTTGGACTCCGTGTGGTCATGGTGGGTGTAGATGTAGCTACTGGCTTTTCAC                   AGAGCACCTCAACTTCACCCCTGGAACCTGGCACAATTCAGCTTAGTGCCCACAGGGG                   CCTCTACCATGACTTCTGGGAGGAGCAAGTAGAGACCGGGCAGACACACCATCCAGAT                   TTGGTGGCGGCATTCCATCCAGGTTTTCATTCCTCCCCAGACTTGATGGAGGCTTGGC                   TGCCCACCCTGCTGCTACTTCGTGACTATAAGATTCCTACATTGATTACTGTTTACAG                   CCATCAGGAGTTGGTATCCTCTTTGCAGATTCTGGTGGAACTGGATACACACATCACT                   GCCTTTGGGTCTAATCCTTTCATGTCCCTCAAACCTGAACAGGTCTATTCCAGTCCCA                   ACAAGCAGCCAGTATACTGCAGTGCATACTATATCATGTTTCTTGGAAGCTCCTGTCA                   GCTGGATAATAGGCAATTAGAAGAGAAAGTGGACGGCGGGATT TAA   ATAGATCATAAC                       TGGACATCTGGAAAACGGGGAGTTTGTGATGAAATTACCCTGCTAATGCCAGGTTCTT                       GCAAACTTTGAAAAACATTATATTCTAAACCTCATTTACTGTTTGGGTAAAAATTCTA                       AGCTGAATGAGAGTTTCTGTATAACATAACTGGTTTCTTTCTTTTTTTGAGATGGAGT                       CTTGCTCTGTTGCCCAGGCTGGAGTGCAGCGGCATGATCTCGACTCACTGCAGCCTCC                       GCCTCCTGGGTTCAAGTGGTTCTCCTGCCTCAGCCTCCCTAGTAGCTGGGATTACAGG                       TGCACACCACCACACCTGGCTAATTTTTGTATTTTTAGCAGACAGGGTTTCACCATGT                       TGGCCAGGCTCGTATCAAACCCTTGACC                                       ORF Start: ATG at 56   ORF Stop: TAA at 1436           SEQ ID NO:76   460 aa MW at 51288.3 kD                     NOV35a,   MAPRSRRRRHKKPPSSVAPIIMAPTTIVTPVPLTPSKPGPSIDTLGFFSLDDNVPGLS               CG148240-01   QLILQKLNMKSYEEYKLVVDGGTPVSGFGFRCPQEMFQRMEDTFRFCAHCRALPSGLS               Protein Sequence   DSKVLRHCKRCRNVYYCGPECQKSDWPAHRRVCQELRLVAVDRLNEWLLVTGDFVLPS                   GPWPWPPEAVQDWDSWFSMKGLHLDATLDAVLVSHAVTTLWASVGRPRPDPDVLQGSL                   KRLLTDVLSRPLTLGLGLRALGIDVRRTGGSTVHVVGASHVETFLTRPGDYDELGYMF                   PGHLGLRVVMVGVDVATGFSQSTSTSPLEPGTIQLSAHRGLYEDFWEEQVETGQTHHP                   DLVAAFHPGFHSSPDLMEAWLPTLLLLRDYKIPTLITVYSHQELVSSLQILVELDTHI                   TAFGSNPFMSLKPEQVYSSPNKQPVYCSAYYIMFLGSSCQLDNRQLEEKVDGGI                  
 
     [0478] Further analysis of the NOV35a protein yielded the following properties shown in Table 35B.  
               TABLE 35B                       Protein Sequence Properties NOV35a                                                PSort   0.5500 probability located in endoplasmic           analysis:   reticulum (membrane); 0.2832               probability located in lysosome (lumen);               0.2287 probability located in               microbody (peroxisome); 0.1000               probability located in endoplasmic               reticulum (lumen)           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0479] A search of the NOV35a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 35C.  
               TABLE 35C                          Geneseq Results for NOV35a                                         NOV35a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent #,   Match   the Matched   Expect       Identifier   Date]   Residues   Region   Value               AAU21785   Novel human neoplastic disease    88 . . . 152   22/66 (33%)   6e−05           associated polypeptide #218 -  Homo     29 . . . 88   30/66 (45%)             sapiens , 246 aa. [WO200155163-A1,           02 Aug. 2001]       AAB74604   Human hBop-m protein sequence    88 . . . 152   22/66 (33%)   6e−05           SEQ ID NO: 7 -  Homo sapiens , 433   34 . . . 93   30/66 (45%)           aa. [CN1272540-A, 08 Nov. 2000]       ABB03929   Human musculoskeletal system    88 . . . 152   22/66 (33%)   6e−05           related polypeptide SEQ ID NO 1876 -   29 . . . 88   30/66 (45%)             Homo sapiens , 246 aa.           [WO200155367-A1, 02 Aug. 2001]       AAB21035   Human nucleic acid-binding protein,    88 . . . 152   22/66 (33%)   6e−05           NuABP-39 -  Homo sapiens , 433 aa.   34 . . . 93   30/66 (45%)           [WO200044900-A2, 03 Aug. 2000]       AAB42760   Human ORFX ORF2524 polypeptide    88 . . . 152   22/66 (33%)   6e−05           sequence SEQ ID NO: 5048 -  Homo     30 . . . 89   30/66 (45%)             sapiens , 429 aa. [WO200058473-A2,           05 Oct. 2000]                  
 
     [0480] In a BLAST search of public sequence datbases, the NOV35a protein was found to have homology to the proteins shown in the BLASTP data in Table 35D.  
               TABLE 35D                          Public BLASTP Results for NOV35a                                         NOV35a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9D5Z5   4833444M15RIK PROTEIN -     1 . . . 444   353/444 (79%)    0.0             Mus musculus  (Mouse), 446 aa.     1 . . . 443   392/444 (87%)        Q9NRG4   HSKM-B -  Homo sapiens      88 . . . 152   22/66 (33%)   1e−04           (Human), 433 aa.   34 . . . 93   30/66 (45%)       AAH23119   SIMILAR TO HSKM-B   105 . . . 152   20/48 (41%)   4e−04           PROTEIN -  Mus musculus     52 . . . 93   24/48 (49%)           (Mouse), 433 aa.       Q9VU41   CG11253 PROTEIN -  Drosophila     100 . . . 149   20/50 (40%)   5e−04             melanogaster  (Fruit fly), 451 aa.   407 . . . 448   26/50 (52%)       Q96E35   SIMILAR TO RIKEN CDNA   124 . . . 151   15/28 (53%)   0.001           2700064H14 GENE -  Homo     187 . . . 214   21/28 (74)                sapiens  (Human), 227 aa.                  
 
     [0481] PFam analysis predicts that the NOV35a protein contains the domains shown in the Table 35E.  
               TABLE 35E                          Domain Analysis of NOV35a                                 NOV35a   Identities/           Pfam   Match   Similarities   Expect       Domain   Region   for the Matched Region   Value               zf-MYND   105 . . . 149   19/47 (40%)   2.5e−09               34/47 (72%)                  
 
     Example 36  
     [0482] The NOV36 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 36A.  
               TABLE 36A                       NOV36 Sequence Analysis                                                SEQ ID NO:77   1130 bp                     NOV36a,     ATG TGTACAAACCCTGAAATTAAACAAGAAGACCCCACAAATGTGGGGCCTGAATGAA               CG59975-01   AGCAACAAGTAACCATGGTTTCAGACACTGAAATCTTAAAGGTAGCTAGAACACATCA               DNA sequence   CGTCCAAGCAGAAAGCTACCTGGTGTACAACATCATGAGCAGTGGAGAGATTGAATGC                   AGCAACACCCTAGAAGATGAGCTTGACCAGGCCTTACCCAGCCAGGCCTTCATTTACC                   GTCCCATTCGACAGCGGGTCTACTCACTCTTACTGGAGGACTGTCAAGATGTCACCAG                   CACCTGCCTAGCTGTCAAGGAGTGGTTTGTGTATCCTGGGAACCCACTGAGGCACCCG                   GACCTCGTCAGGCCGCTGCAGATGACCATTCCAGGGGGAACGCCTAGTTTGAAAATAT                   TATGGCTGAACCAAGAGCCAGAAATACAGGTTCGGCGCTTGGACACACTCCTAGCCTG                   TTTCAATCTTTCCTCCTCAAGAGAAGAGCTGCAGGCTGTCGAAAGCCCATTTCAAGCT                   TTGTGCTGCCTCTTGATCTACCTCTTTGTCCAGGTGGACACGCTTTGCCTGGAGGATT                   TGCATGCGTTTATTGCGCAGGCCTTGTGCCTCCAAGGAAAATCCACCTCGCAGCTTGT                   AAATCTACAGCCTGATTACATCAACCCCAGAGCCGTGCAGCTGGGCTCCCTTCTCGTC                   CGCGGCCTCACCACTCTGGTTTTAGTCAACAGCGCATGTGGCTTCCCCTGGAAGACGA                   GTGATTTCATGCCCTGGAATGTATTTGACGGGAAGCTTTTTCATCAGAAGTACTTGCA                   ATCTGAAAAGGGTTATGCTGTGGAGGTTCTTTTAGAACAAAATAGATCTCGGCTCACC                   AAATTCCACAACCTGAAGGCAGTCGTCTGCAAGGCCTGCATGAAGGAGAACAGACGCA                   TCACTGGCCGAGCCCACTGGGGCTCACACCACGCAGGGAGGTGGGGAAGACAGGGCTC                   CAGCTACCACAGGACGGGCTCTGGGTATAGCCGTTCCAGTCAGGGACAGCCGTGGAGA                   GACCAGGGACCAGGAAGCAGACAGTATGAGCATGACCAGTGGAGAAGGTAC TAG   TCAA                       CCTCCAGGTAAGTTCATCACCTGCATCT                                       ORF Start: ATG at 1   ORF Stop: TAG at 1096           SEQ ID NO:78   365 aa MW at 41672.1 kD                     NOV36a,   MCTNPEIKQEDPTNVGPEVKQQVTMVSDTEILKVARTHHVQAESYLVYNIMSSGEIEC               CG59975-01   SNTLEDELDQALPSQAFIYRPIRQRVYSLLLEDCQDVTSTCLAVKEWFVYPGNPLRHP               Protein Sequence   DLVRPLQMTIPGGTPSLKILWLNQEPEIQVRRLDTLLACFNLSSSREELQAVESPFQA                   LCCLLIYLFVQVDTLCLEDLHAFIAQALCLQGKSTSQLVNLQPDYINPRAVQLGSLLV                   RGLTTLVLVNSACGFPWKTSDFMPWNVFDGKLFHQKYLQSEKGYAVEVLLEQNRSRLT                   KFHNLKAVVCKACMKENRRITGRAHWGSHHAGRWGRQGSSYHRTGSGYSRSSQGQPWR                   DQGPGSRQYEHDQWRRY                                     SEQ ID NO:79   1124 bp                     NOV36b,   TTATGTGTACAAACCCTGAAATTAAACAAGAAGACCCCACAAATGTGGGGCCTGAAGT               CG59975-02   AAAGCAACAAGTAACCATGGTTTCAGACACTGAAATCTTAAAGGTTGCTAGAACACAT               DNA Sequence   CACGTCCAAGCAGAAAGCTACCTGGTGTACAACATCATGAGCAGTGGAGAGATTGAAT                   GCAGCAACACCCTAGAAGATGAGCTTGACCAGGCCTTACCCAGCCAGGCCTTCATTTA                   CCGTCCCATTCGACAGCGGGTCTACTCACTCTTACTGGAGGACTGTCAAGATGTCACC                   AGCACCTGCCTAGCTGTCAAGGAGTGGTTTGTGTATCCTGGGAACCCACTGAGGCACC                   CGGACCTCGTCAGGCCGCTGCAGATGACCATTCCAGGGGGAACGCCTAGTTTGAAAAT                   ATTATGGCTGAACCAAGAGCCAGAAATACAGGTTCGGCGCTTGGACACACTCCTAGCC                   TGTTTCAATCTTTCCTCCTCAAGAGAAGAGCTGCAGGCTGTCGAAAGCCCATTTCAAG                   CTTTGTGCTGCCTCTTGATCTACCTCTTTGTCCAGGTGGACACGCTTTGCCTGGAGGA                   TTTGCATGCGTTTATTGCGCAGGCCTTGTGCCTCCAAGGAAAATCCACCTCGCAGCTT                   GTAAATCTACAGCCTGATTACATCAACCCCAGAGCCGTGCAGCTGGGCTCCCTTCTCG                   TCCGCGGCCTCACCACTCTGGTTTTAGTCAACAGCGCATGTGGCTTCCCCTGGAAGAC                   GAGTGATTTCATGCCCTGGAATGTATTTGACGGGAAGCTTTTTCATCAGAAGTACTTG                   CAATCTGAAAAGGGTTATGCTGTGGAGGTTCTTTTAGAACAAAATAGATCTCGGCTCA                   CCAAATTCCACAACCTGAAGGCAGTCGTCTGCAAGGCCTGCATGAAGGAGAACAGACG                   CATCACTGGCCGAGCCCACTGGGGCTCACACCACGCAGGGAGGTGGGGAAGACAGGGC                   TCCAGCTACCACAGGACGGGCTCTGGGTATAGCCGTTCCAGTCAGGGACAGCCGTGGA                   GAGACCAAGGACCAGGAAGCAGACAGTATGAGCATGACCAGTGGAGAAGGTAC TAG   TC                       AACCTCCAGGTAAGTTCATCAC                                       ORF Start: ATG at 3   ORF Stop: TAG at 1098           SEQ ID NO:80   365 aa MW at 41672.1 kD                     NOV36b,   MCTNPEIKQEDPTNVGPEVKQQVTMVSDTEILKVARTHHVQAESYLVYNIMSSGEIEC               CG59975-02   SNTLEDELDQALPSQAFIYRPIRQRVYSLLLEDCQDVTSTCLAVKEWFVYPGNPLRHP               Protein Sequence   DLVRPLQMTIPGGTPSLKILWLNQEPEIQVRRLDTLLACFNLSSSREELQAVESPFQA                   LCCLLIYLFVQVDTLCLEDLHAFIAQALCLQGKSTSQLVNLQPDYINPRAVQLGSLLV                   RGLTTLVLVNSACGFPWKTSDFMPWNVFDGKLFHQKYLQSEKGYAVEVLLEQNRSRLT                   KFHNLKAVVCKACMKENRRITGRAHWGSHHAGRWGRQGSSYHRTGSGYSRSSQGQPWR                   DQGPGSRQYEHDQWRRY                  
 
     [0483] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 36B.  
               TABLE 36B                          Comparison of NOV36a against NOV36b.                         Protein   NOV36a Residues/   Identities/       Sequence   Match Residues   Similarities for the Matched Region               NOV36b   1 . . . 365   350/365 (95%)           1 . . . 365   350/365 (95%)                  
 
     [0484] Further analysis of the NOV36a protein yielded the following properties shown in Table 36C.  
               TABLE 36C                       Protein Sequence Properties NOV36a                                                PSort   0.8500 probability located in endoplasmic reticulum           analysis:   (membrane); 0.4400 probability located in plasma               membrane; 0.3044 probability located in microbody               (peroxisome); 0.1000 probability located in               mitochondrial inner membrane           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0485] A search of the NOV36a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 36D.  
               TABLE 36D                          Geneseq Results for NOV36a                                         NOV36a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAU19923   Novel human calcium-binding     1 . . . 365   331/365 (90%)   0.0           protein #32 -  Homo sapiens , 486   156 . . . 486   331/365 (90%)           aa. [WO200155304-A2, 02 Aug.           2001]       AAW85612   Secreted protein clone fh123_5 -     1 . . . 285    285/285 (100%)   e−166             Homo sapiens , 916 aa.   546 . . . 830    285/285 (100%)           [WO9849302-A1, 05 Nov. 1998]       ABB12073   Human secreted protein     1 . . . 281    281/281 (100%)   e−164           homologue, SEQ ID NO: 2443 -   578 . . . 858    281/281 (100%)             Homo sapiens , 915 aa.           [WO200157188-A2, 09 Aug.           2001]       AAY53673   Protein 405_hum sequence used    30 . . . 274    87/266 (32%)   1e−30           for clustral X alignment -  Rattus     554 . . . 816   134/266 (49%)             sp , 1118 aa. [WO9960164-A1,           25 Nov. 1999]       AAY53670   Mechanical stress induced protein    30 . . . 274    87/266 (32%)   1e−30           405 amino acid sequence -  Rattus     554 . . . 816   134/266 (49%)             sp , 1118 aa. [WO9960164-A1,           25 Nov. 1999]                  
 
     [0486] In a BLAST search of public sequence datbases, the NOV36a protein was found to have homology to the proteins shown in the BLASTP data in Table 36E.  
               TABLE 36E                          Public BLASTP Results for NOV36a                                         NOV36a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96EK7   UNKNOWN (PROTEIN FOR   1 . . . 365    365/365 (100%)   0.0           MGC: 20434) -  Homo sapiens     546 . . . 910      365/365 (100%)           (Human), 910 aa.       Q96JI9   KIAA1838 PROTEIN -  Homo     1 . . . 365    365/365 (100%)   0.0             sapiens  (Human), 917 aa   553 . . . 917      365/365 (100%)           (fragment).       Q9N061   UNNAMED PROTEIN   1 . . . 365   356/365 (97%)   0.0           PRODUCT -  Macaca fascicularis     1 . . . 365   361/365 (98%)           (Crab eating macaque)           (Cynomolgus monkey), 365 aa.       Q99LL4   RIKEN CDNA 4932442K08   1 . . . 365   294/365 (80%)   e−170           GENE -  Mus musculus  (Mouse),   1 . . . 362   321/365 (87%)           362 aa.       Q9D4F4   4932442K08RIK PROTEIN -  Mus     1 . . . 365   293/365 (80%)   e−170             musculus  (Mouse), 362 aa.   1 . . . 362   321/365 (87%)                  
 
     [0487] PFam analysis predicts that the NOV36a protein contains the domains shown in the Table 36F.  
               TABLE 36F                       Domain Analysis of NOV36a                                                        Pfam   NOV36a   Identities/   Expect           Domain   Match   Similarities   Value               Region   for the Matched Region                      
 
     Example 37  
     [0488] The NOV37 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 37A.  
               TABLE 37A                       NOV37 Sequence Analysis                                                SEQ ID NO:81   1173 bp                     NOV37a,     GCATACTATTACATTACAGCTTATA   ATG GCAACCCCTGAAGAAAACAGCAATCCCCAT               CG89947-01   GACAGAGCAACACCCCAGCTGCCAGCACAGCTGCAGGAGCTTGAGCATCGGGTGGCCC               DNA Sequence   GGAGACGGCTGTCCCAGGCCCGCCACCGAGCCACCCTGGCAGCGCTCTTCAACAACCT                   CAGGAAGACAGTGTACTCTCAGTCTGATCTCATAGCCTCAAAGTGGCAGGTTCTGAAT                   AAGGCAAAGAGTCATATTCCAGAACTGGAGCAAACCCTGGATAATTTGCTGAAGCTGA                   AAGCATCCTTCAACCTGGAAGATGGGCATGCAAGCAGCTTAGAGGAGGTCAAGAAAGA                   ATATGCCAGCATGTATTCTGGAAATGACAGCCTGCTTTCAAACAGTTTTCCTCAGAAT                   GGTTCCTCCCCTTGGTGCCCAACTGAGGCAGTCAGGAAGGATGCTGAGGAGGAGGAAG                   ATGAGGAAGAGGAAGATCAAGAAGAAGAGGAGGAGGAAGAAGAAGAGGAGGAGGAGGA                   GGAAGAGGAGGAAGAGGAAGAGGAGGAGGAGGAAGAGGAGAAAAAAGTGATCTTATAC                   TCCCCAGGAACTTTGTCGCCTGACCTCATGGAATTTGAACGGTATCTCAACTTTTACA                   AACAGACGATGGACCTTCTGACTGGCAGCGGGATCATTACCCCGCAGGAGGCGGCGCT                   GCCCATCGTCTCCGCGGCCATCTCCCACCTGTGGCAGAACCTCTCGGAGGAGAGGAAG                   GCCAGCCTCCGGCAGGCCTGGGCGCAGAAGCACCGCGGCCCTGCGACCCTGGCGGAGG                   CCTGCCGAGAGCCGGCCTGTGCCGAGGGCAGCGTGAAGGACAGCGGCGTGGACAGCCA                   GGGGGCCAGCTGCTCGCTGGTCTCCACGCCCGAGGAGATCCTTTTTGAGGATGCCTTT                   GATGTGGCAAGCTTCCTGGACAAAAGTGAGGTTCCGAGTACATCTAGCTCCAGTTCAG                   TGCTTGCCAGCTGCAACCCAGAAAACCCAGAGGAGAAGTTTCAGCTCTATATGCAGAT                   CATCAACTTTTTTAAAGGCCTTAGCTGTGCAAACACTCAAGTAAAGCAGGAAGCATCC                   TTTCCCGTTGATGAAGAGATGATCATGTTGCAGTGCACAGAGACCTTTGACGATGAAG                   ATTTG TAA   TGCAG                                       ORF Start: ATG at 26   ORF Stop: TAA at 1166           SEQ ID NO: 82   380 aa MW at 42845.4 kD                     NOV37a,   MATPEENSNPHDRATPQLPAQLQELEHRVARRRLSQARHRATLAALFNNLRKTVYSQS               CG89947-01   DLIASKWQVLNKAKSHIPELEQTLDNLLKLKASFNLEDGHASSLEEVKKEYASMYSGN               Protein Sequence   DSLLSNSFPQNGSSPWCPTEAVRKDAEEEEDEEEEDQEEEEEEEEEEEEEEEEEEEEE                   EEEEEKKVILYSPGTLSPDLMEFERYLNFYKQTMDLLTGSGIITPQEAALPIVSAAIS                   HLWQNLSEERKASLRQAWAQKHRGPATLAEACREPACAEGSVKDSGVDSQGASCSLVS                   TPEEILFEDAFDVASFLDKSEVPSTSSSSSVLASCNPENPEEKFQLYMQIINFFKGLS                   CANTQVKQEASFPVDEEMIMLQCTETFDDEDL                                     SEQ ID NO:83   1178 bp                     NOV37b,     ATG GCAACCCCTAAAGAAAACAGCAATCCCCATGACAGAGCAACACCCCAGCTGCCAG               CG89947-02   CACAGCTGCAGGAGCTTGAGCATCGGGTGGCCCGGAGACGGCTGTCCCAGGCCCGCCA               DNA Sequence   CCGAGCCACCCTGGCAGCACTCTTCAACAACCTCAGGAAGACAGTGTACTCTCAGTCT                   GATCTCATAGCCTCAAAGTGGCAGGTTCTGAATAAGGCAAAGAGTCATATTCCAGAAC                   TGGAGCAAACCCTGGATAATTTGCTGAAGCTGAAAGCATCCTTCAACCTGGAAGATGG                   GCATGCAAGCAGCTTAGAGGAGGTCAAGAAAGAATATGCCAGCATGTATTCTGGAAAT                   GACAGCCTGCTTTCAAACAGTTTTCCTCAGAATGGTTCCTCCCCTTGGTGCCCAACTG                   AGGCAGTCAGGAAGGATGCTGAGGAGGAGGAAGATGAGGAAGAGGAAGATCAAGAAGA                   AGAGGAGGAGGAAGAAGAAGAGGAGGAGGAGGAGGAAGAGGAGGAAGAGGAAGAGGAG                   GAGGAGGAAGAGGAGAAAAAAGTGATCTTATACTCCCCAGGAACTTTGTCGCCTGGCC                   TCATGGAATTTGAACGGTATCTCAACTTTTACAAACAGACGATGGACCTTCTGACTGG                   CAGCGGGATCATTACCCCGCAGGAGGCGGCGCTGCCCATCGTCTCCGCGGCCATCTCC                   CACCTGTGGCAGAACCTCTCGGAGGAGAGGAAGGCCAGCCTCCGGCAGGCCTGGGCGC                   AGAAGCACCGCGGCCCTGCGACCCTGGCGGAGGCCTGCCGAGAGCCGGCCTGTGCCGA                   GGGCAGCGTGAAGGACAGCGGCGTGGACAGCCAGGGGGCCAGCTGCTCGCTGGTCTCC                   ACGCCCGAGGAGATCCTTTTTGAGGATGCCTTTGATGTGGCAAGCTTCCTGGACAAAA                   GTGAGGTTCCGAGTACATCTAGCTCCAGTTCAGTGCTTGCCAGCTGCAACCCAGAAAA                   CCCAGAGGAGAAGTTTCAGCTCTATATGCAGATCATCAACTTTTTTAAAGGCCTTAGC                   TGTGCAAACACTCAAGTAAAGCAGGAAGCATCCTTTCCCGTTGATGAAGAGATGATCA                   TGTTGCAGTGTACAGAGACCTTTGACGATGAAGATTTG TAA   TGCCAGGGTTTGCTGTT                       TTCTTAAGGGGTTGCCAT                                       ORF Start: ATG at 1   ORF Stop: TAA at 1141           SEQ ID NO:84   380 aa MW at 42786.4 kD                     NOV37b,   MATPKENSNPHDRATPQLPAQLQELEHRVARRRLSQARHRATLAALFNNLRKTVYSQS               CG89947-02   DLIASKWQVLNKAKSHIPELEQTLDNLLKLKASFNLEDGHASSLEEVKKEYASMYSGN               Protein Sequence   DSLLSNSFPQNGSSPWCPTEAVRKDAEEEEDEEEEDQEEEEEEEEEEEEEEEEEEEEE                   EEEEEKKVILYSPGTLSPGLMEPERYLNFYKQTMDLLTGSGIITPQEAALPIVSAAIS                   TPEEILFEDAFDVASFLDKSEVPSTSSSSSVLASCNPENPEEKFQLYMQIINFFKGLS                   CANTQVKQEASFPVDEEMIMLQCTETFDDEDL                  
 
     [0489] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 37B.  
               TABLE 37B                          Comparison of NOV37a against NOV37b.                         Protein   NOV37a Residues/   Identities/       Sequence   Match Residues   Similarities for the Matched Region               NOV37b   1 . . . 380   326/380 (85%)           1 . . . 380   327/380 (85%)                  
 
     [0490] Further analysis of the NOV37a protein yielded the following properties shown in Table 37C.  
               TABLE 37C                       Protein Sequence Properties NOV37a                                        Psort   0.4500 probability located in cytoplasm; 0.3000 probability located in       analysis:   microbody (peroxisome); 0.1000 probability located in mitochondrial matrix           space; 0.1000 probability located in lysosome (lumen)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0491] A search of the NOV37a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 37D.  
               TABLE 37D                          Geneseq Results for NOV37a                                             Identities/                   NOV37a   Similarities               Residues/   for the       Geneseq   Protein/Organism/Length [Patent   Match   Matched   Expect       Identifier   #, Date]   Residues   Region   Value               ABG11278   Novel human diagnostic protein   124 . . . 179   39/56 (69%)   2e−14           #11269 -  Homo sapiens , 62 aa.    6 . . . 61   45/56 (79%)           [WO200175067-A2, 11-OCT-2001]       ABG11278   Novel human diagnostic protein   124 . . . 179   39/56 (69%)   2e−14           #11269 -  Homo sapiens , 62 aa.    6 . . . 61   45/56 (79%)           [WO200175067-A2, 11-OCT-2001]       ABG06956   Novel human diagnostic protein   143 . . . 193   35/51 (68%)   3e−12           #6947 -  Homo sapiens , 58 aa.    4 . . . 54   41/51 (79%)           [WO200175067-A2, 11-OCT-2001]       ABG04384   Novel human diagnostic protein   143 . . . 193   35/51 (68%)   3e−12           #4375 -  Homo sapiens , 58 aa.    4 . . . 54   41/51 (79%)           [WO200175067-A2, 11-OCT-2001]       ABG06956   Novel human diagnostic protein   143 . . . 193   35/51 (68%)   3e−12           #6947 -  Homo sapiens , 58 aa.    4 . . . 54   41/51 (79%)           [WO200175067-A2, 11-OCT-2001]                  
 
     [0492] In a BLAST search of public sequence datbases, the NOV37a protein was found to have homology to the proteins shown in the BLASTP data in Table 37E.  
               TABLE 37E                          Public BLASTP Results for NOV37a                                         NOV37a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               P70278   STRA8 PROTEIN -  Mus musculus      1 . . . 377   262/392 (66%)    e−138           (Mouse), 393 aa.    1 . . . 392   295/392 (74%)       AAL92605   HYPOTHETICAL 96.2 KDA    52 . . . 179    51/128 (39%)   5e−13           PROTEIN -  Dictyostelium     710 . . . 796    71/128 (54%)             discoideum  (Slime mold), 806 aa.       BAB90435   OSJNBB0006H05.12 PROTEIN -     83 . . . 180    37/98 (37%)   7e−10             Oryza sativa  (japonica cultivar-    49 . . . 146    54/98 (54%)           group), 157 aa.       Q96MU7   CDNA FLJ31868 FIS, CLONE    70 . . . 181    45/112 (40%)   2e−09           NT2RP7001962, HIGHLY    92 . . . 195    66/112 (58%)           SIMILAR TO  RATTUS               NORVEGICUS  YT521 RNA           SPLICING-RELATED PROTEIN -              Homo sapiens  (Human), 658 aa.       O35788   CYCLIC NUCLEOTIDE-GATED   103 . . . 181    30/79 (37%)   1e−08           CHANNEL BETA SUBUNIT -    398 . . . 476    51/79 (63%)             Rattus norvegicus  (Rat), 1339 aa.                  
 
     [0493] PFam analysis predicts that the NOV37a protein contains the domains shown in the Table 37F.  
               TABLE 37F                          Domain Analysis of NOV37a                                     Identities/                   Similarities           NOV37a   for the        Pfam Domain   Match Region   Matched Region   Expect Value               HLH   31 . . . 79   16/57 (28%)   0.17               32/57 (56%)                  
 
     Example 38  
     [0494] The NOV38 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 38A.  
               TABLE 38A                       NOV38 Sequence Analysis                                                SEQ ID NO:85   2490 bp                     NOV38a,     ATG TTTCACCTGAAGGACGCTGAAATGGGAGCCTTTACCTTCTTTGCCTCGGCTCTGC               CG03366-02   CACATGATGTTTGTGGAAGCAATGGACTTCCTCTCACACCAAATTCCATCAAAATTTT               DNA Sequence   AGGGCGCTTTCAAATCCTTAAAACCATCACCCATCCCAGACTCTGCCAGTATGTGGAT                   ATTTCTAGGGGAAAGCATGAACGACTAGTGGTCGTGGCTGAACATTGTGAACGTAGTC                   TGGAAGACTTGCTTCGAGAAAGGAAACCTGTGAGGTATCCCTCGTACTTGGCCCCTGA                   GGTAATTGCACAGGGAATTTTCAAAACCACTGATCACATGCCAAGTAAAAAACCATTG                   CCTTCTGGCCCCAAATCAGATGTATGGTCTCTTGGAATCATTTTATTTGAGCTTTGTG                   TGGGAAGAAAATTATTTCAGAGCTTGGATATTTCTGAAAGACTAAAATTTTTGCTTAC                   TTTGGATTGTGTAGATGACACTTTAATAGTTCTGGCTGAAGAGCATGGGTGTTTGGAC                   ATTATAAAGGAGCTTCCTGAAACTGTGATAGATCTTTTGAATAAGTGCCTTACCTTCC                   ATCCTTCTAAGAGGCCAACCCCAGATGAATTAATGAAGGACAAAGTATTCAGTGAGGT                   ATCACCTTTATATACCCCCTTTACCAAACCTGCCAGTCTGTTTTCATCTTCTCTGAGA                   TGTGCTGATTTAACTCTGCCTGAGGATATCAGTCAGTTGTGTAAAGATATAAATAATG                   ATTACCTGGCAGAAAGATCTATTGAAGAAGTGTATTACCTTTGGTGTTTGGCTGGAGG                   TGACTTGGAGAAAGAGCTTGTCAACAAGGAAATCATTCGATCCAAACCACCTATCTGC                   ACACTCCCCAATTTTCTCTTTGAGGATGGTGAAAGCTTTGGACAAGGTCGAGATAGAA                   GCTCGCTTTTAGATGATACCACTGTGACATTGTCGTTATGCCAGCTAAGAAATAGATT                   GAAAGATGTTGGTGGAGAAGCATTTTACCCATTACTTGAAGATGACCAGTCTAATTTA                   CCTCATTCAAACAGCAATAATGAGTTGTCTGCAGCTGCCATGCTCCCTTTAATCATCA                   GAGAGAAGGATACAGAGTACCAACTAAATAGAATTATTCTCTTCGACAGGCTAAAGGC                   TTATCCATATAAAAAAAACCAAATCTGGAAAGAAGCAAGAGTTGACATTCCTCCTCTT                   ATGAGAGGTTTAACCTGGGCTGCTCTTCTGGGAGTTGAGGGAGCTATTCATGCCAAGT                   ACGATGCAATTGATAAAGACACTCCAATTCCTACAGATAGACAAATTGAAGTGGATAT                   TCCTCGCTGTCATCAGTACGATGAACTGTTATCATCACCAGAAGGTCATGCAAAATTT                   AGGCGTGTATTAAAAGCCTGGGTAGTGTCTCATCCTGATCTTGTGTATTGGCAAGGTC                   TTGACTCACTTTGTGCTCCATTCCTATATCTAAACTTCAATAATGAAGCCTTGGCTTA                   TGCATGTATGTCTGCTTTTATTCCCAAATACCTGTATAACTTCTTCTTAAAAGACAAC                   TCACATGTAATACAAGAGTATCTGACTGTCTTCTCTCAGATGATTGCATTTCATGATC                   CAGAGCTGAGTAATCATCTCAATCAGATTGGCTTCATTCCAGATCTCTATGCCATCCC                   TTGGTTTCTTACCATGTTTACTCATGTATTTCCACTACACAAAATTTTCCACCTCTGG                   GATACCTTACTACTTGGGAATTCCTCTTTCCCATTCTGTATTGGAGTAGCAATTCTTC                   AGCAGCTGCGGGACCGGCTTTTGGCTAATGGCTTTAATGAGTGTATTCTTCTCTTCTC                   CGATTTACCAGAAATTGACATTGAACGCTGTGTGAGAGAATCTATCAACCTGTTTTGT                   TGGACTCCTAAAAGTGCTACTTACAGACAGCATGCTCAACCTCCAAAGCCATCTTCTG                   ACAGCAGTGGAGGCAGAAGTTCGGCACCTTATTTCTCTGCTGAGTGTCCAGATCCTCC                   AAAGACAGATCTGTCAAGAGAATCCATCCCATTAAATGACCTGAAGTCAGAAGTATCA                   CCACGGATTTCAGCAGAGGACCTGATTGACTTGTGTGAGCTCACAGTGACAGGCCACT                   TCAAAACACCCAGCAAGAAAACAAAGTCCAGTAAACCAAAGCTCCTGGTGGTTGACAT                   CCTGAATAGTGAAGACTTTATTCGTGGTCACATTTCAGGAAGCATCAACATTCCATTC                   AGTGCTGCCTTCACTGCAGAAGGGGAGCTTACCCAGGGCCCTTACACTGCTATGCTCC                   AGAACTTCAAAGGGAAGGTCATTGTCATCGTGGGGCATGTGGCAAAACACACAGCTGA                   GTTTGCAGCTCACCTTGTGAAGATGAAATATCCAAGAATCTGTATTCTAGATGGTGGC                   ATTAATAAAATAAAGCCAACAGGCCTCCTCACCATCCCATCTCCTCAAATA TGA                                       ORF Start: ATG at 1   ORF Stop: TGA at 2488           SEQ ID NO: 86   829 aa MW at 93637.7 kD                     NOV38a,   MFHLKDAEMGAFTFFASALPHDVCGSNGLPLTPNSIKILGRFQILKTITHPRLCQYVD               CG93366-02   ISRGKHERLVVVAEHCERSLEDLLRERKPVRYPSYLAPEVIAQGIFKTTDHMPSKKPL               Protein Sequnce   PSGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDCVDDTLIVLAEEHGCLD                   IIKELPETVIDLLNKCLTFHPSKRPTPDELMKDKVFSEVSPLYTPFTKPASLFSSSLR                   CADLTLPEDISQLCKDINNDYLAERSIEEVYYLWCLAGGDLEKELVNKEIIRSKPPIC                   TLPNFLFEDGESFGQGRDRSSLLDDTTVTLSLCQLRNRLKDVGGEAFYPLLEDDQSNL                   PHSNSNNELSAAAMLPLIIREKDTEYQLNRIILFDRLKAYPYKKNQIWKEARVDIPPL                   MRGLTWAALLGVEGAIHAKYDAIDKDTPIPTDRQIEVDIPRCHQYDELLSSPEGHAKF                   RRVLKAWVVSHPDLVYWQGLDSLCAPFLYLNFNNEALAYACMSAFIPKYLYNFFLKDN                   SHVIQEYLTVFSQMIAFHDPELSNHLNQIGFIPDLYAIPWFLTMFTHVFPLHKIFHLW                   DTLLLGNSSFPFCIGVAILQQLRDRLLANGFNECILLFSDLPEIDIERCVRESINLFC                   WTPKSATYRQHAQPPKPSSDSSGGRSSAPYFSAECPDPPKTDLSRESIPLNDLKSEVS                   PRISAEDLIDLCELTVTGHFKTPSKKTKSSKPKLLVVDILNSEDFIRGHISGSINIPF                   SAAFTAEGELTQGPYTAMLQNFKGKVIVIVGHVAKHTAEFAAHLVKMKYPRTCILDGG                   INKIKPTGLLTIPSPQI                  
 
     [0495] Further analysis of the NOV38a protein yielded the following properties shown in Table 38B.  
               TABLE 38B                       Protein Sequence Properties NOV38a                                                PSort   0.8500 probability located in endoplasmic           analysis:   reticulum (membrane); 0.4400               probability located in plasma membrane;               0.3362 probability located in               microbody (peroxisome); 0.1000 probability               located in mitochondrial inner               membrane           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0496] A search of the NOV38a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 38C.  
               TABLE 38C                          Geneseq Results for NOV38a                                         NOV38a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length [Patent   Match   the Matched   Expect       Identifier   #, Date]   Residues   Region   Value               AAB62179   Human p100 protein -  Homo      87 . . . 829   741/743 (99%)   0.0             sapiens , 892 aa. [WO200120022-   150 . . . 892   742/743 (99%)           A1, 22-MAR-2001]       AAB98890   Novel human (NHP) protein that    87 . . . 829   738/744 (99%)   0.0           has homology to animal kinases -    150 . . . 893   740/744 (99%)             Homo sapiens , 893 aa.           [WO200134783-A1, 17-MAY-2001]       AAG67396   Amino acid sequence of human    87 . . . 829   738/744 (99%)   0.0       `   protein kinase SGK382 -  Homo     150 . . . 893   740/744 (99%)             sapiens , 893 aa. [WO200166594-           A2, 13-SEP-2001]       ABB07503   Human GTP-binding protein   198 . . . 829   629/633 (99%)   0.0           (GTPB) (ID: 3580727CD1) -  Homo      4 . . . 636   630/633 (99%)             sapiens , 636 aa. [WO200204510-           A2, 17-JAN-2002]       AAM38995   Human polypeptide SEQ ID NO:   205 . . . 829   610/627 (97%)   0.0           2140 -  Homo sapiens , 627 aa.    1 . . . 627   612/627 (97%)           [WO200153312-A1, 26-JUL-2001]                  
 
     [0497] In a BLAST search of public sequence datbases, the NOV38a protein was found to have homology to the proteins shown in the BLASTP data in Table 38D.  
               TABLE 38D                          Public BLASTP Results for NOV38a                                         NOV38a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96GV6   UNKNOWN (PROTEIN FOR    9 . . . 829   818/822 (99%)   0.0           MGC: 16169) -  Homo sapiens      1 . . . 822   819/822 (99%)           (Human), 822 aa.       BAB85045   CDNA FLJ23725 FIS, CLONE    87 . . . 829   738/744 (99%)   0.0           HEP14024 -  Homo sapiens     150 . . . 893   740/744 (99%)           (Human), 893 aa.       Q9P080   HSPC302 -  Homo sapiens     325 . . . 829   479/507 (94%)   0.0           (Human), 507 aa (fragment).    1 . . . 507   481/507 (94%)       Q9W4F8   CG4041 PROTEIN -  Drosophila      5 . . . 802   353/854 (41%)   e−169             melanogaster  (Fruit fly), 840 aa.    8 . . . 794   468/854 (54%)       Q8WW57   SIMILAR TO HYPOTHETICAL   543 . . . 829   285/287 (99%)   e−167           PROTEIN MGC16169 -  Homo      14 . . . 300   286/287 (99%)             sapiens  (Human), 300 aa           (fragment).                  
 
     [0498] PFam analysis predicts that the NOV38a protein contains the domains shown in the Table 38E.  
               TABLE 38E                          Domain Analysis of NOV38a                                     Identities/                   Similarities           NOV38a   for the   Expect       Pfam Domain   Match Region   Matched Region   Value               pkinase    93 . . . 210    38/140 (27%)   2e−17                87/140 (62%)       TBC   399 . . . 609    63/343 (18%)   1e−26               153/343 (45%)       Rhodanese   712 . . . 819    29/136 (21%)   0.00039                76/136 (56%)                  
 
     Example 39  
     [0499] The NOV39 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 39A.  
               TABLE 39A                       NOV39 Sequence Analysis                                                SEQ ID NO:87   1136 bp                     NOV39a,     ACACCTTTCTAAAAAGACTCCCTGTGGTGTTCAGAATCACTCCTACAGTCAGGTTCTC                 CG97068-02     CACA   ATG GATCTCAGTGCTGCAAGTCACCGCATACCTCTAAGTGATGGAAACAGCATT               DNA Sequence   CCCATCATCGGACTTGGTACCTACTCAGAACCTAAATCGACCCCTAAGGGAGCCTGTG                   CAACATCGGTGAAGGTTGCTATTGACACAGGGTACCGACATATTGATGGGGCCTACAT                   CTACCAAAATGAACACGAAGTTGGGGAGGCCATCAGGGAGAAGATAGCAGAAGGAAAG                   GTGCGGAGGGAAGATATCTTCTACTGTGGAAAGCTATGGGCTACAAATCATGTCCCAG                   AGATGGTCCGCCCAACCCTGGAGAGGACACTCAGGGTCCTCCAGCTAGATTATGTGGA                   TCCTTACATCATTGAAGTACCCATGGCCTTTAAGCCAGGAGATGAAATATACCCTAGA                   GATGAGAATGGCAAATGGTTATATCACAAGTCAGATCTGTGTGCCACTTGGGAGGCGA                   TGGAAGCTTGCAAAGACGCTGGCTTGGTGAAATCCCTGGGAGTGTCCAATTTTAACCG                   CAGGCAGCTGGAGCTCATCCTGAACAAGCCAGGACTCAAACACAAGCCAGTCAGCAAC                   CAGGTTGAGTGCCATCCGTATTTCACCCAGCCAAAACTCTTGAAATTTTGCCAACAAC                   ATGACATTGTCATTACTGCATATAGCCCTTTGGGGACCAGTAGGAATCCAATCTCGGT                   GAATGTTTCTTCTCCACCTTTGTTAAAGGATGCACTTCTAAACTCATTGGGGAAAAGG                   TACAATAAGACAGCAGCTCAAATTGTTTTGCGTTTCAACATCCAGCGAGGGGTGGTTG                   TCATTCCTAAAAGCTTTAATCTTGAAAGGATCAAAGAAAATTTTCAGATCTTTGACTT                   TTCTCTCACTGAAGAAGAAATGAAGGACATTGAAGCCTTGAATAAAAATGTCCGCTTT                   GTAGAATTGCTCATGTGGCGCGATCATCCTGAATACCCATTTCATGATGAATAC TGA   C                       TGCCGGGAGTTCCTGAACAGATTTTTCACTCCCATGAGTCCCAAGACGGTGCAATGGG                       TAGTCCCCTAGATGTGAAAATGAAGAGAGAGGGT                                       ORF Start: ATG at 63   ORF Stop: TGA at 1041           SEQ ID NO:88   326 aa MW at 37361.5 kD                     NOV39a,   MDLSAASHRIPLSDGNSIPIIGLGTYSEPKSTPKGACATSVKVAIDTGYRHIDGAYIY               CG97068-02   QNEHEVGEAIREKIAEGKVRREDIFYCGKLWATNHVPEMVRPTLERTLRVLQLDYVDP               Protein Sequence   YIIEVPMAFKPGDEIYPRDENGKWLYHKSDLCATWEAMEACKDAGLVKSLGVSNFNRR                   QLELILNKPGLKHKPVSNQVECHPYFTQPKLLKFCQQHDIVITAYSPLGTSRNPIWVN                   VSSPPLLKDALLNSLGKRYNKTAAQIVLRFNIQRGVVVIPKSFNLERIKENFQIFDFS                   LTEEEMKDIEALNKNVRFVELLMWRDHPEYPFHDEY                  
 
     [0500] Further analysis of the NOV39a protein yielded the following properties shown in Table 39B.  
               TABLE 39B                          Protein Sequence Properties NOV39a                             PSort   0.6500 probability located in cytoplasm;           analysis:   0.1000 probability located in               mitochondrial matrix space; 0.1000               probability located in lysosome (lumen);               0.0000 probability located in endoplasmic               reticulum (membrane)           SignalP   No Known Signal Sequence Predicted           analysis:                      
 
     [0501] A search of the NOV39a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 39C.  
               TABLE 39C                          Geneseq Results for NOV39a                                         NOV39a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABG06369   Novel human diagnostic protein    1 . . . 326   324/326 (99%)   0.0           #6360 -  Homo sapiens , 347 aa.   22 . . . 347   325/326 (99%)           [WO200175067-A2, 11-OCT-2001]       ABG06369   Novel human diagnostic protein    1 . . . 326   324/326 (99%)   0.0           #6360 -  Homo sapiens , 347 aa.   22 . . . 347   325/326 (99%)           [WO200175067-A2, 11-OCT-2001]       AAR55551   Delta(4)-3-ketosteroid-5-beta-    1 . . . 326   257/327 (78%)   e−153           reductase - Synthetic, 326 aa.    1 . . . 326   290/327 (88%)           [JP06121673-A, 06-MAY-1994]       AAB43444   Human cancer associated protein   10 . . . 326   184/317 (58%)   e−109           sequence SEQ ID NO: 889 -  Homo     21 . . . 336   240/317 (75%)             sapiens , 336 aa. [WO200055350-           A1, 21-SEP-2000]       AAM79455   Human protein SEQ ID NO: 3101 -    10 . . . 326   178/317 (56%)   e−107             Homo sapiens , 325 aa.   10 . . . 325   238/317 (74%)           [WO200157190-A2, 09-AUG-2001]                  
 
     [0502] In a BLAST search of public sequence datbases, the NOV39a protein was found to have homology to the proteins shown in the BLASTP data in Table 39D.  
               TABLE 39D                          Public BLASTP Results for NOV39a                                         NOV39a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               P51857   3-oxo-5-beta-steroid 4-   1 . . . 326   324/326 (99%)   0.0           dehydrogenase (EC 1.3.99.6)   1 . . . 326   325/326 (99%)           (Delta(4)-3-ketosteroid 5-beta-           reductase) (Aldo-keto reductase           family 1 member D1) -  Homo               sapiens  (Human), 326 aa.       Q9TV64   DELTA4-3-OXOSTEROID 5BETA-   1 . . . 326   290/326 (88%)   e−178           REDUCTASE -  Oryctolagus     1 . . . 326   310/326 (94%)             cuniculus  (Rabbit), 326 aa.       Q8VCX1   SIMILAR TO ALDO-KETO   1 . . . 326   267/326 (81%)   e−159           REDUCTASE FAMILY 1,   1 . . . 325   293/326 (88%)           MEMBER D1 (DELTA 4-3-           KETOSTEROID-5-BETA-           REDUCTASE) -  Mus musculus             (Mouse), 325 aa.       P31210   3-oxo-5-beta-steroid 4-   1 . . . 326   258/327 (78%)   e−153           dehydrogenase (EC 1.3.99.6)   1 . . . 326   291/327 (88%)           (Delta(4)-3-ketosteroid 5-beta-           reductase) (Aldo-keto reductase           family 1 member D1) -  Rattus               norvegicus  (Rat), 326 aa.       P70694   Estradiol 17 beta-dehydrogenase, A-   3 . . . 326   190/324 (58%)   e−111           specific (EC 1.1.1.-) (17-beta-HSD) -    1 . . . 323   241/324 (73%)             Mus musculus  (Mouse), 323 aa.                  
 
     [0503] PFam analysis predicts that the NOV39a protein contains the domains shown in the Table 39E.  
               TABLE 39E                          Domain Analysis of NOV39a                                 NOV39a   Identities/               Match   Similarities   Expect       Pfam Domain   Region   for the Matched Region   Value               aldo_ket_red   12 . . . 306   154/368 (42%)   1.5e−146               262/368 (71%)                  
 
     Example B  
     [0504] Identification of NOVX Clones  
     [0505] The novel NOVX target sequences identified in the present invention may have been subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the predicted exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain—amygdala, brain—cerebellum, brain—hippocampus, brain—substantia nigra, brain—thalamus, brain—whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma—Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus.  
     [0506] Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation&#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.  
     Example C  
     [0507] Quantitative Expression Analysis of Clones in Various Cells and Tissues  
     [0508] The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoinflammatory diseases), Panel CNSD.01 (containing samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer&#39;s diseased brains).  
     [0509] 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.  
     [0510] 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.  
     [0511] 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.  
     [0512] 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.  
     [0513] 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.  
     [0514] When working with sscDNA samples, normalized sscDNA was used as described previously for RNA samples. PCR reactions containing one or two sets of probe and primers were set up as described previously, using 1× TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer&#39;s instructions. PCR amplification was performed as follows: 95° C. 10 min, then 40 cycles of 95° C. for 15 seconds, 60° C. for 1 minute. Results were analyzed and processed as described previously.  
     [0515] Panels 1, 1.1, 1.2, and 1.3D  
     [0516] 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.  
     [0517] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:  
     [0518] ca.=carcinoma,  
     [0519] *=established from metastasis,  
     [0520] met=metastasis,  
     [0521] s cell var=small cell variant,  
     [0522] non-s=non-sm=non-small,  
     [0523] squam=squamous,  
     [0524] pl. eff=pl effusion=pleural effusion,  
     [0525] glio=glioma,  
     [0526] astro=astrocytoma, and  
     [0527] neuro=neuroblastoma.  
     [0528] General_screening_panel_v1.4, v1.5 and v1.6  
     [0529] The plates for Panels 1.4, 1.5, and 1.6 include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panels 1.4, 1.5, and 1.6 are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in Panels 1.4, 1.5, and 1.6 are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on Panels 1.4, 1.5, and 1.6 are comprised of pools of samples derived from all major organ systems from 2 to 5 different adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose. Abbreviations are as described for Panels 1, 1.1, 1.2, and 1.3D.  
     [0530] Panels 2D, 2.2, 2.3 and 2.4  
     [0531] The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include 2 control wells and 94 test samples composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute&#39;s Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI) or from Ardais or Clinomics). The tissues are derived from human malignancies and in cases where indicated many malignant tissues have “matched margins” obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted “NAT” in the results below. The tumor tissue and the “matched margins” are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues without malignancy (normal tissues) were also obtained from Ardais or Clinomics. This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, Calif.), Research Genetics, and Invitrogen.  
     [0532] HASS Panel v 1.0  
     [0533] The HASS panel v 1.0 plates are comprised of 93 cDNA samples and two controls. Specifically, 81 of these samples are derived from cultured human cancer cell lines that had been subjected to serum starvation, acidosis and anoxia for different time periods as well as controls for these treatments, 3 samples of human primary cells, 9 samples of malignant brain cancer (4 medulloblastomas and 5 glioblastomas) and 2 controls. The human cancer cell lines are obtained from ATCC (American Type Culture Collection) and fall into the following tissue groups: breast cancer, prostate cancer, bladder carcinomas, pancreatic cancers and CNS cancer cell lines. These cancer cells are all cultured under standard recommended conditions. The treatments used (serum starvation, acidosis and anoxia) have been previously published in the scientific literature. The primary human cells were obtained from Clonetics (Walkersville, Md.) and were grown in the media and conditions recommended by Clonetics. The malignant brain cancer samples are obtained as part of a collaboration (Henry Ford Cancer Center) and are evaluated by a pathologist prior to CuraGen receiving the samples. RNA was prepared from these samples using the standard procedures. The genomic and chemistry control wells have been described previously.  
     [0534] Panel 3D and 3.1  
     [0535] The plates of Panel 3D and 3.1 are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines, 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma of the tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D, 3.1 and 1.3D are of the most common cell lines used in the scientific literature.  
     [0536] Panels 4D, 4R, and 4.1D  
     [0537] 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.).  
     [0538] 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.  
     [0539] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 31 5 M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2×10 6  cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10 −5 M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.  
     [0540] 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, UT), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), 10 mM Hepes (Gibco) and 10% AB Human Serum or MCSF at approximately 50 ng/ml. Monocytes, macrophages and dendritic cells were stimulated for 6 and 12-14 hours with lipopolysaccharide (LPS) at 100 ng/ml. Dendritic cells were also stimulated with anti-CD40 monoclonal antibody (Pharmingen) at 10 μg/ml for 6 and 12-14 hours.  
     [0541] CD4 lymphocytes, CD8 lymphocytes and NK cells were also isolated from mononuclear cells using CD4, CD8 and CD56 Miltenyi beads, positive VS selection columns and a Vario Magnet according to the manufacturer&#39;s instructions. CD45RA and CD45RO CD4 lymphocytes were isolated by depleting mononuclear cells of CD8, CD56, CD14 and CD19 cells using CD8, CD56, CD14 and CD19 Miltenyi beads and positive selection. CD45RO beads were then used to isolate the CD45RO CD4 lymphocytes with the remaining cells being CD45RA CD4 lymphocytes. CD45RA CD4, CD45RO CD4 and CD8 lymphocytes were placed in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco) and plated at 10 6  cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0.5 μg/ml anti-CD28 (Pharmingen) and 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 −5 M (Gibco), and 10 mM Hepes (Gibco) and IL-2. The expanded CD8 cells were then activated again with plate bound anti-CD3 and anti-CD28 for 4 days and expanded as before. RNA was isolated 6 and 24 hours after the second activation and after 4 days of the second expansion culture. The isolated NK cells were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.  
     [0542] To obtain B cells, tonsils were procured from NDRI. The tonsil was cut up with sterile dissecting scissors and then passed through a sieve. Tonsil cells were then spun down and resupended at 10 6  cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 (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.  
     [0543] To prepare the primary and secondary Th1/Th2 and Tr1 cells, six-well Falcon plates were coated overnight with 10 μg/ml anti-CD28 (Pharmingen) and 2 μg/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic Systems, German Town, Md.) were cultured at 10 5 -10 6  cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5  M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4 ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 μg/ml) were used to direct to Th1, while IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct to Tr1. After 4-5 days, the activated Th1, Th2 and Tr1 lymphocytes were washed once in DMEM and expanded for 4-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), 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.  
     [0544] The following leukocyte cells lines were obtained from the ATCC: Ramos, EOL-1, KU-812. EOL cells were further differentiated by culture in 0.1 mM dbcAMP at 5×10 5  cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×10 5  cells/ml. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco). CCD 1106 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.  
     [0545] For these cell lines and blood cells, RNA was prepared by lysing approximately 10 7  cells/ml using Trizol (Gibco BRL). Briefly, 1/10 volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 5 μl DTT, 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with 1/10 volume of 3M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at −80° C.  
     [0546] AI_comprehensive panel_v1.0  
     [0547] 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.  
     [0548] 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.  
     [0549] 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.  
     [0550] 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.  
     [0551] Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD was purchased from Clinomics. Emphysema patients ranged in age from 40-70 and all were smokers, this age range was chosen to focus on patients with cigarette-linked emphysema and to avoid those patients with alpha-1anti-trypsin deficiencies. Asthma patients ranged in age from 36-75, and excluded smokers to prevent those patients that could also have COPD. COPD patients ranged in age from 35-80 and included both smokers and non-smokers. Most patients were taking corticosteroids, and bronchodilators.  
     [0552] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:  
     [0553] AI=Autoimmunity  
     [0554] Syn=Synovial  
     [0555] Normal=No apparent disease  
     [0556] Rep22 /Rep20=individual patients  
     [0557] RA=Rheumatoid arthritis  
     [0558] Backus=From Backus Hospital  
     [0559] OA=Osteoarthritis  
     [0560] (SS)(BA)(MF)=Individual patients  
     [0561] Adj=Adjacent tissue  
     [0562] Match control=adjacent tissues  
     [0563] −M=Male  
     [0564] −F=Female  
     [0565] COPD=Chronic obstructive pulmonary disease  
     [0566] Panels 5D and 51  
     [0567] 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.  
     [0568] In the Gestational Diabetes study subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (&lt;1 cc) of the exposed metabolic tissues during the closure of each surgical level. The biopsy material was rinsed in sterile saline, blotted and fast frozen within 5 minutes from the time of removal. The tissue was then flash frozen in liquid nitrogen and stored, individually, in sterile screw-top tubes and kept on dry ice for shipment to or to be picked up by CuraGen. The metabolic tissues of interest include uterine wall (smooth muscle), visceral adipose, skeletal muscle (rectus) and subcutaneous adipose. Patient descriptions are as follows:  
     [0569] Patient 2: Diabetic Hispanic, overweight, not on insulin  
     [0570] Patient 7-9: Nondiabetic Caucasian and obese (BMI&gt;30)  
     [0571] Patient 10: Diabetic Hispanic, overweight, on insulin  
     [0572] Patient 11: Nondiabetic African American and overweight  
     [0573] Patient 12: Diabetic Hispanic on insulin  
     [0574] Adiocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr. 2, 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:  
     [0575] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose  
     [0576] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated  
     [0577] Donor 2 and 3 AD: Adipose, Adipose Differentiated  
     [0578] 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.  
     [0579] 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.  
     [0580] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:  
     [0581] GO Adipose=Greater Omentum Adipose  
     [0582] SK=Skeletal Muscle  
     [0583] UT=Uterus  
     [0584] PL=Placenta  
     [0585] AD Adipose Differentiated  
     [0586] AM=Adipose Midway Differentiated  
     [0587] U=Undifferentiated Stem Cells  
     [0588] Panel CNSD.01  
     [0589] 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.  
     [0590] 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 Supemuclear 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.  
     [0591] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:  
     [0592] PSP=Progressive supranuclear palsy  
     [0593] Sub Nigra=Substantia nigra  
     [0594] Glob Palladus=Globus palladus  
     [0595] Temp Pole=Temporal pole  
     [0596] Cing Gyr=Cingulate gyrus  
     [0597] BA 4=Brodman Area 4  
     [0598] Panel CNS_Neurodegeneration_V1.0  
     [0599] 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.  
     [0600] Disease diagnoses are taken from patient records. The panel contains six brains from Alzheimei&#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.  
     [0601] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:  
     [0602] AD=Alzheimer&#39;s disease brain; patient was demented and showed AD-like pathology upon autopsy  
     [0603] Control=Control brains; patient not demented, showing no neuropathology  
     [0604] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology  
     [0605] SupTemporal Ctx=Superior Temporal Cortex  
     [0606] Inf Temporal Ctx=Inferior Temporal Cortex  
     A. CG100570-01: LRR Protein (Novel Secreted Protein)  
     [0607] Expression of gene CG100570-01 was assessed using the primer-probe set Ag4181, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB, AC, AD, AE and AF.  
               TABLE AA                          Probe Name Ag4181                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-agttaagaggaaatgccattgg-3′   22   3338   89               Probe   TET-5′-agccaaagccctggcaaatgctct-3′-TAMRA   24   3369   90               Reverse   5′-tccggagacttgagtttacctt-3′   22   3394   91                  
 
     [0608]               TABLE AB                          AI_comprehensive panel_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4181,       Ag4181,       Tissue Name   Run 212650186   Tissue Name   Run 212650186                                     110967 COPD-F   2.9   112427 Match Control   12.8               Psoriasis-F       110980 COPD-F   4.4   112418 Psoriasis-M   2.9       110968 COPD-M   4.6   112723 Match Control   3.1               Psoriasis-M       110977 COPD-M   12.5   112419 Psoriasis-M   1.9       110989   13.6   112424 Match Control   2.2       Emphysema-F       Psoriasis-M       110992   7.2   112420 Psoriasis-M   21.9       Emphysema-F       110993   6.8   112425 Match Control   8.0       Emphysema-F       Psoriasis-M       110994   3.2   104689 (MF) OA   8.9       Emphysema-F       Bone-Backus       110995   15.5   104690 (MF) Adj   3.3       Emphysema-F       “Normal” Bone-Backus       110996   4.6   104691 (MF) OA   2.2       Emphysema-F       Synovium-Backus       110997 Asthma-M   4.0   104692 (BA) OA   2.7               Cartilage-Backus       111001 Asthma-F   6.7   104694 (BA) OA   4.5               Bone-Backus       111002 Asthma-F   8.5   104695 (BA) Adj   4.0               “Normal” Bone-               Backus       111003 Atopic   6.9   104696 (BA) OA   1.0       Asthma-F       Synovium-Backus       111004 Atopic   10.4   104700 (SS) OA   4.7       Asthma-F       Bone-Backus       111005 Atopic   4.8   104701 (SS) Adj   3.8       Asthma-F       “Normal” Bone-               Backus       111006 Atopic   1.7   104702 (SS) OA   5.4       Asthma-F       Synovium-Backus       111417 Allergy-M   5.8   117093 OA Cartilage   6.8               Rep7       112347 Allergy-M   0.2   112672 OA Bone5   13.9       112349 Normal   0.1   112673 OA   3.6       Lung-F       Synovium5       112357 Normal   13.4   112674 OA Synovial   5.7       Lung-F       Fluid cells5       112354 Normal Lung-M   4.9   117100 OA Cartilage   0.8               Rep14       112374 Crohns-F   0.0   112756 OA Bone9   1.0       112389 Match   4.2   112757 OA   3.6       Control Crohns-F       Synovium9       112375 Crohns-F   5.0   112758 OA Synovial   3.1               Fluid Cells9       112732 Match   58.2   117125 RA Cartilage   4.2       Control Crohns-F       Rep2       112725 Crohns-M   0.7   113492 Bone2 RA   17.8       112387 Match   2.8   113493 Synovium2   5.4       Control Crohns-M       RA       112378 Crohns-M   0.1   113494 Syn Fluid   9.8               Cells RA       112390 Match   21.6   113499 Cartilage4 RA   12.7       Control Crohns-M       112726 Crohns-M   6.4   113500 Bone4 RA   14.4       112731 Match   4.8   113501 Synovium4   7.6       Control Crohns-M       RA       112380 Ulcer Col-F   5.7   113502 Syn Fluid   6.7               Cells4 RA       112734 Match   100.0   113495 Cartilage3 RA   7.0       Control Ulcer Col-F       112384 Ulcer Col-F   22.7   113496 Bone3 RA   10.7       112737 Match   2.2   113497 Synovium3   6.8       Control Ulcer Col-F       RA       112386 Ulcer Col-F   3.1   113498 Syn Fluid   13.5               Cells3 RA       112738 Match   4.0   117106 Normal   3.2       Control Ulcer Col-F       Cartilage Rep20       112381 Ulcer Col-M   0.3   113663 Bone3 Normal   0.0       112735 Match   2.7   113664 Synovium3   0.0       Control Ulcer Col-M       Normal       112382 Ulcer Col-M   6.0   113665 Syn Fluid   0.2               Cells3 Normal       112394 Match   1.3   117107 Normal   2.9       Control Ulcer Col-M       Cartilage Rep22       112383 Ulcer Col-M   9.9   113667 Bone4 Normal   7.1       112736 Match   1.3   113668 Synovium4   4.2       Control Ulcer Col-M       Normal       112423 Psoriasis-F   4.2   113669 Syn Fluid Cells4   6.6               Normal                    
     [0609]               TABLE AC                          CNS_neurodegeneration_v1.0                                 Rel.       Rel.           Exp. (%)       Exp. (%)           Ag4181,       Ag4181,           Run       Run       Tissue Name   215539691   Tissue Name   215539691                                     AD 1 Hippo   31.0   Control (Path) 3   3.2               Temporal Ctx       AD 2 Hippo   26.1   Control (Path) 4   28.5               Temporal Ctx       AD 3 Hippo   12.3   AD 1 Occipital Ctx   23.7       AD 4 Hippo   4.0   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   93.3   AD 3 Occipital Ctx   9.9       AD 6 Hippo   60.7   AD 4 Occipital Ctx   6.7       Control 2 Hippo   8.2   AD 5 Occipital Ctx   20.7       Control 4 Hippo   15.5   AD 6 Occipital Ctx   9.5       Control (Path) 3   4.7   Control 1 Occipital   6.2       Hippo       Ctx       AD 1 Temporal Ctx   20.3   Control 2 Occipital   47.3               Ctx       AD 2 Temporal Ctx   21.5   Control 3 Occipital   13.5               Ctx       AD 3 Temporal Ctx   11.0   Control 4 Occipital   12.2               Ctx       AD 4 Temporal Ctx   40.9   Control (Path) 1   100.0               Occipital Ctx       AD 5 Inf Temporal   94.0   Control (Path) 2   21.9       Ctx       Occipital Ctx       AD 5 Sup Temporal   52.9   Control (Path) 3   1.5       Ctx       Occipital Ctx       AD 6 Inf Temporal   45.1   Control (Path) 4   20.6       Ctx       Occipital Ctx       AD 6 Sup Temporal   85.9   Control 1 Parietal Ctx   12.1       Ctx       Control 1 Temporal   4.1   Control 2 Parietal Ctx   45.1       Ctx       Control 2 Temporal   29.5   Control 3 Parietal Ctx   20.6       Ctx       Control 3 Temporal   3.9   Control (Path) 1   32.1       Ctx       Parietal Ctx       Control 3 Temporal   9.7   Control (Path) 2   22.2       Ctx       Parietal Ctx       Control (Path) 1   37.6   Control (Path) 3   4.4       Temporal Ctx       Parietal Ctx       Control (Path) 2   38.7   Control (Path) 4   54.7       Temporal Ctx       Parietal Ctx                    
     [0610]               TABLE AD                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4181,       Ag4181, Run       Tissue Name   Run 212717379   Tissue Name   212717379                                     Adipose   11.7   Renal ca. TK-10   7.9       Melanoma*   1.6   Bladder   19.8       Hs688(A).T       Melanoma*   0.8   Gastric ca. (liver met.)   27.7       Hs688(B).T       NCI-N87       Melanoma* M14   1.3   Gastric ca. KATO III   2.6       Melanoma*   2.4   Colon ca. SW-948   2.2       LOXIMVI       Melanoma* SK-MEL-5   1.8   Colon ca. SW480   6.2       Squamous cell   0.4   Colon ca.* (SW480 met)   5.1       carcinoma SCC-4       SW620       Testis Pool   11.3   Colon ca. HT29   0.8       Prostate ca.* (bone   1.9   Colon ca. HCT-116   9.4       met) PC-3       Prostate Pool   7.2   Colon ca. CaCo-2   6.3       Placenta   3.2   Colon cancer tissue   7.2       Uterus Pool   3.3   Colon ca. SW1116   4.6       Ovarian ca. OVCAR-3   1.9   Colon ca. Colo-205   0.0       Ovarian ca. SK-OV-3   21.9   Colon ca. SW-48   0.9       Ovarian ca. OVCAR-4   1.3   Colon Pool   29.5       Ovarian ca. OVCAR-5   30.4   Small Intestine Pool   3.1       Ovarian ca. IGROV-1   5.0   Stomach Pool   14.9       Ovarian ca. OVCAR-8   3.9   Bone Marrow Pool   12.5       Ovary   11.8   Fetal Heart   14.4       Breast ca. MCF-7   5.3   Heart Pool   12.2       Breast ca. MDA-MB-   6.3   Lymph Node Pool   26.8       231       Breast ca. BT 549   1.7   Fetal Skeletal Muscle   7.4       Breast ca. T47D   36.1   Skeletal Muscle Pool   14.5       Breast ca. MDA-N   0.5   Spleen Pool   55.1       Breast Pool   25.2   Thymus Pool   100.0       Trachea   26.1   CNS cancer (glio/astro)   0.8               U87-MG       Lung   3.2   CNS cancer (glio/astro)   6.6               U-118-MG       Fetal Lung   55.1   CNS cancer (neuro; met)   5.4               SK-N-AS       Lung ca. NCI-N417   0.8   CNS cancer (astro) SF-   0.7               539       Lung ca. LX-1   11.2   CNS cancer (astro) SNB-   6.1               75       Lung ca. NCI-H146   1.9   CNS cancer (glio) SNB-   2.4               19       Lung ca. SHP-77   5.8   CNS cancer (glio) SF-   18.0               295       Lung ca. A549   5.7   Brain (Amygdala) Pool   3.3       Lung ca. NCI-H526   0.5   Brain (cerebellum)   15.0       Lung ca. NCI-H23   20.9   Brain (fetal)   13.5       Lung ca. NCI-H460   8.1   Brain (Hippocampus)   3.7               Pool       Lung ca. HOP-62   1.8   Cerebral Cortex Pool   7.3       Lung ca. NCI-H522   6.7   Brain (Substantia nigra)   6.2               Pool       Liver   1.8   Brain (Thalamus) Pool   10.0       Fetal Liver   6.0   Brain (whole)   5.2       Liver ca. HepG2   3.4   Spinal Cord Pool   9.3       Kidney Pool   32.5   Adrenal Gland   5.3       Fetal Kidney   23.2   Pituitary gland Pool   2.9       Renal ca. 786-0   2.9   Salivary Gland   5.5       Renal ca. A498   9.0   Thyroid (female)   5.9       Renal ca. ACHN   6.7   Pancreatic ca. CAPAN2   6.5       Renal ca. UO-31   6.2   Pancreas Pool   30.1                    
     [0611]               TABLE AE                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4181, Run       Ag4181, Run       Tissue Name   173607818   Tissue Name   173607818                                     Secondary Th1 act   34.6   HUVEC IL-1beta   0.6       Secondary Th2 act   35.6   HUVEC IFN gamma   1.6       Secondary Tr1 act   35.8   HUVEC TNF alpha +   0.2               IFN gamma       Secondary Th1 rest   35.8   HUVEC TNF alpha +   0.1               IL4       Secondary Th2 rest   49.7   HUVEC IL-11   0.7       Secondary Tr1 rest   64.6   Lung Microvascular EC   6.3               none       Primary Th1 act   12.8   Lung Microvascular EC   1.3               TNF alpha + IL-1beta       Primary Th2 act   27.5   Microvascular Dermal   0.3               EC none       Primary Tr1 act   16.7   Microsvasular Dermal   0.3               EC TNF alpha + IL-1beta       Primary Th1 rest   37.9   Bronchial epithelium   0.2               TNF alpha + IL1beta       Primary Th2 rest   33.2   Small airway epithelium   0.1               none       Primary Tr1 rest   54.3   Small airway epithelium   0.1               TNF alpha + IL-1beta       CD45RA CD4   10.7   Coronery artery SMC   0.3       lymphocyte act       rest       CD45RO CD4   36.1   Coronery artery SMC   0.0       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   27.9   Astrocytes rest   0.5       Secondary CD8   19.3   Astrocytes TNF alpha +   0.1       lymphocyte rest       IL-1beta       Secondary CD8   18.8   KU-812 (Basophil) rest   5.4       lymphocyte act       CD4 lymphocyte none   28.7   KU-812 (Basophil)   4.9               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   100.0   CCD1106   0.2       CD95 CH11       (Keratinocytes) none       LAK cells rest   21.9   CCD1106   0.4               (Keratinocytes)               TNF alpha + IL-1beta       LAK cells IL-2   44.4   Liver cirrhosis   0.5       LAK cells IL-2 + IL-12   19.1   NCI-H292 none   0.3       LAK cells IL-2 + IFN   14.5   NCI-H292 IL-4   0.5       gamma       LAK cells IL-2 + IL-18   24.7   NCI-H292 IL-9   1.0       LAK cells   4.7   NCI-H292 IL-13   0.8       PMA/ionomycin       NK Cells IL-2 rest   90.1   NCI-H292 IFN gamma   0.9       Two Way MLR 3 day   29.5   HPAEC none   0.9       Two Way MLR 5 day   13.4   HPAEC TNF alpha + IL-   0.7               1beta       Two Way MLR 7 day   24.8   Lung fibroblast none   1.1       PBMC rest   19.8   Lung fibroblast TNF   0.4               alpha + IL-1beta       PBMC PWM   14.8   Lung fibroblast IL-4   0.6       PBMC PHA-L   16.6   Lung fibroblast IL-9   0.6       Ramos (B cell) none   32.8   Lung fibroblast IL-13   1.0       Ramos (B cell)   32.5   Lung fibroblast IFN   0.4       ionomycin       gamma       B lymphocytes PWM   8.8   Dermal fibroblast   3.4               CCD1070 rest       B lymphocytes CD40L   29.7   Dermal fibroblast   55.5       and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   21.6   Dermal fibroblast   0.2               CCD1070 IL-1beta       EOL-1 dbcAMP   20.4   Dermal fibroblast IFN   0.8       PMA/ionomycin       gamma       Dendritic cells none   2.2   Dermal fibroblast IL-4   0.3       Dendritic cells LPS   0.9   Dermal fibroblasts rest   0.2       Dendritic cells anti-   0.0   Neutrophils TNFa + LPS   0.5       CD40       Monocytes rest   0.4   Neutrophils rest   0.9       Monocytes LPS   1.9   Colon   1.3       Macrophages rest   3.4   Lung   2.6       Macrophages LPS   0.5   Thymus   31.6       HUVEC none   0.6   Kidney   10.2       HUVEC starved   1.3                    
     [0612]               TABLE AF                          general oncology screening panel_v_2.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4181,       Ag4181,       Tissue Name   Run 260271995   Tissue Name   Run 260271995                                     Colon cancer 1   16.5   Bladder cancer NAT 2   0.7       Colon NAT 1   10.0   Bladder cancer NAT 3   0.6       Colon cancer 2   8.0   Bladder cancer NAT 4   0.6       Colon cancer NAT 2   3.0   Adenocarcinoma of the   41.2               prostate 1       Colon cancer 3   6.2   Adenocarcinoma of the   0.9               prostate 2       Colon cancer NAT 3   6.8   Adenocarcinoma of the   5.0               prostate 3       Colon malignant   14.9   Adenocarcinoma of the   4.6       cancer 4       prostate 4       Colon normal adjacent   3.0   Prostate cancer NAT 5   1.1       tissue 4       Lung cancer 1   20.4   Adenocarcinoma of the   2.3               prostate 6       Lung NAT 1   0.8   Adenocarcinoma of the   1.8               prostate 7       Lung cancer 2   30.1   Adenocarcinoma of the   1.3               prostate 8       Lung NAT 2   3.4   Adenocarcinoma of the   9.7               prostate 9       Squamous cell   18.8   Prostate cancer NAT 10   1.4       carcinoma 3       Lung NAT 3   0.4   Kidney cancer 1   27.9       metastatic melanoma 1   12.9   Kidney NAT 1   15.2       Melanoma 2   1.5   Kidney cancer 2   100.0       Melanoma 3   0.7   Kidney NAT 2   4.7       metastatic melanoma 4   17.0   Kidney cancer 3   21.9       metastatic melanoma 5   33.0   Kidney NAT 3   2.0       Bladder cancer 1   0.7   Kidney cancer 4   9.7       Bladder cancer NAT 1   0.0   Kidney NAT 4   1.4       Bladder cancer 2   3.3                    
     [0613] AI_comprehensive panel_v1.0 Summary: Ag4181 Highest expression of the CG100570-01 gene is seen in normal tissue adjacent to a disease sample of ulcerative colitis (CT=29.3). Overall, this gene is widely expressed on this panel, supporting the suggestion that this gene product may be involved in the autoimmune respones. Please see Panel 4.1D for discussion of this gene in autoimmune disease.  
     [0614] CNS_neurodegeneration_v1.0 Summary: Ag4181 The CG100570-01 gene appears to be upregulated in the temporal cortex of Alzheimer&#39;s disease patients. Therefore, therapeutic modulation of the expression or function of this protein may decrease neuronal death and be of use in the treatment of this disease.  
     [0615] General_screening_panel_v1.4 Summary: Ag4181 Highest expression of the CG100570-01 gene is seen in the thymus (CT=29.3). Significant levels of expression are also seen in ovarian cancer, breast cancer, and lung cancer cell lines. In addition, higher levels of expression are seen in fetal lung (CT=30.1) when compared to expression in the adult lung (CT=34). Thus, expression of this gene could be used to differentiate between adult and fetal lung tissue. Since fetal tissue and cell lines are generally more proliferative than adult tissue, this gene may be involved in cell proliferation, particularly in ovarian, breast and lung cancers. Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of ovarian, breast and lung cancer.  
     [0616] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0617] This gene is also expressed at low levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0618] Panel 4.1D Summary: Ag4181 Highest expression of the CG100570-01 gene is seen in secondary Th1/TH2/Tr1 cells treated with anti-CD95 (CT=27.6). The CG100570-01 gene transcript is found in T cells and B cells, including resting and activated Th1, Th2 and Tr1 cells, resting and PWM stimulated B lymphocytes, the Ramos B cell line, PBMCs stimulated with PWM, and the thymus. LAK cells, dendritic cells and eosinophils also express this transcript at moderate levels. Dermal fibroblasts treated with TNF-alpha are the only non-hematopoietic cell type that prominently expresses this transcript. Thus, this transcript or the protein it encodes may be important in the function of B or T cells and could be used to detect hematopoietically-derived cells. Furthermore, therapeutics designed with the protein encoded by this transcript may potentially be important in the treatment of T and B cell mediated diseases, including asthma, emphysema, psoriasis, arthrtis, lupus, and inflammatory bowel disease (IBD).  
     [0619] General oncology screening panel_v — 2.4 Summary: Ag4181 Expression of the CG100570-01 gene is highest in a sample derived from kidney cancer (CT=31.4). In addition, this gene is overexpressed in kidney cancer when compared to corresponding normal adjacent tissue. Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of kidney cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of kidney cancer.  
     B. CG100750-01: LRR Protein (Novel Intracellular Protein)  
     [0620] Expression of gene CG100750-01 was assessed using the primer-probe set Ag4188, described in Table BA. Results of the RTQ-PCR runs are shown in Table BB.  
               TABLE BA                          Probe Name Ag4188                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ggagttctctttcagcaaaggt-3′   22   244   92               Probe   TET-5′-tcctatgttttctatctcagctgcca-3′-TAMRA   26   268   93               Reverse   5′-tcagcaaaggtagtttccttca-3′   22   308   94                  
 
     [0621]               TABLE BB                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4188, Run       Ag4188, Run       Tissue Name   182086762   Tissue Name   182086762                                     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 +   0.0               IFN gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha +   0.0               IL4       Secondary Th2 rest   0.0   HUVEC IL-11   0.0       Secondary Tr1 rest   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   0.0               EC none       Primary Tr1 act   0.0   Microsvasular Dermal   0.0               EC 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   0.0   Coronery artery SMC   0.0       lymphocyte act       rest       CD45RO CD4   0.0   Coronery artery SMC   0.0       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   0.0       Secondary CD8   0.0   Astrocytes TNF alpha +   0.0       lymphocyte rest       IL-1beta       Secondary CD8   0.0   KU-812 (Basophil) rest   0.0       lymphocyte act       CD4 lymphocyte none   0.0   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.0   CCD1106   0.0       CD95 CH11       (Keratinocytes) none       LAK cells rest   0.0   CCD1106   0.0               (Keratinocytes)               TNF alpha + IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   0.0       LAK cells IL-2 + IL-12   0.0   NCI-H292 none   0.0       LAK cells IL-2 + IFN   0.0   NCI-H292 IL-4   0.0       gamma       LAK cells IL-2 + IL-18   0.0   NCI-H292 IL-9   0.0       LAK cells   0.0   NCI-H292 IL-13   0.0       PMA/ionomycin       NK Cells IL-2 rest   0.0   NCI-H292 IFN gamma   0.0       Two Way MLR 3 day   0.0   HPAEC none   0.0       Two Way MLR 5 day   0.0   HPAEC TNF alpha + IL-   0.0               1beta       Two Way MLR 7 day   0.0   Lung fibroblast none   0.0       PBMC rest   0.0   Lung fibroblast TNF   0.0               alpha + IL-1beta       PBMC PWM   0.0   Lung fibroblast IL-4   0.0       PBMC PHA-L   0.0   Lung fibroblast IL-9   0.0       Ramos (B cell) none   0.0   Lung fibroblast IL-13   0.0       Ramos (B cell)   0.0   Lung fibroblast IFN   0.0       ionomycin       gamma       B lymphocytes PWM   0.0   Dermal fibroblast   0.0               CCD1070 rest       B lymphocytes CD40L   0.0   Dermal fibroblast   0.0       and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast   0.0               CCD1070 IL-1beta       EOL-1 dbcAMP   0.0   Dermal fibroblast IFN   2.0       PMA/ionomycin       gamma       Dendritic cells none   0.0   Dermal fibroblast IL-4   0.0       Dendritic cells LPS   0.0   Dermal Fibroblasts rest   0.6       Dendritic cells anti-   0.0   Neutrophils TNFa + LPS   0.0       CD40       Monocytes rest   0.0   Neutrophils rest   0.0       Monocytes LPS   0.0   Colon   1.7       Macrophages rest   0.0   Lung   2.1       Macrophages LPS   0.0   Thymus   6.6       HUVEC none   0.0   Kidney   100.0       HUVEC starved   0.0                    
     [0622] Panel 4.1D Summary: Ag4188 This gene is only expressed at detectable levels in the kidney (CT=32.7). Thus, expression of this gene could be used to differentiate the kidney derived sample from other samples on this panel and as a marker of kidney tissue. In addition, therapeutic targeting of the expression or function of this gene may modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.  
     C. CG101201-01: Novel Adenine Nucleotide Translocator 2 (ADP/ATP Translocase 2)  
     [0623] Expression of gene CG 101201-01 was assessed using the primer-probe set Ag4206, described in Table CA. Results of the RTQ-PCR runs are shown in Table CB.  
               TABLE CA                          Probe Name Ag4206                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ccaaggctctaacaggtctgt-3′   21   553   95               Probe   TET-5′-tatcatctaccgagctgcctgcttcg-3′-TAMRA   26   593   96               Reverse   5′-tctccttgcagtgtcatagaca-3′   22   610   97                  
 
     [0624]               TABLE CB                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4206, Run       Ag4206, Run       Tissue Name   174268918   Tissue Name   174268918                                     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 +   0.0               IFN gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha +   0.0               IL4       Secondary Th2 rest   0.0   HUVEC IL-11   0.0       Secondary Tr1 rest   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   0.0               EC none       Primary Tr1 act   0.0   Microsvasular Dermal   0.0               EC TNF alpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   3.0               TNF alpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium   6.4               none       Primary Tr1 rest   0.0   Small airway epithelium   6.4               TNF alpha + IL-1beta       CD45RA CD4   0.0   Coronery artery SMC   0.0       lymphocyte act       rest       CD45RO CD4   0.0   Coronery artery SMC   0.6       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   0.0       Secondary CD8   0.0   Astrocytes TNF alpha +   1.7       lymphocyte rest       IL-1beta       Secondary CD8   0.0   KU-812 (Basophil) rest   0.0       lymphocyte act       CD4 lymphocyte none   0.0   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.0   CCD1106   73.7       CD95 CH11       (Keratinocytes) none       LAK cells rest   0.0   CCD1106   6.2               (Keratinocytes)               TNF alpha + IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   0.0       LAK cells IL-2 + IL-12   0.0   NCI-H292 none   9.9       LAK cells IL-2 + IFN   0.0   NCI-H292 IL-4   12.2       gamma       LAK cells IL-2 + IL-18   0.0   NCI-H292 IL-9   9.6       LAK cells   0.3   NCI-H292 IL-13   4.9       PMA/ionomycin       NK Cells IL-2 rest   0.0   NCI-H292 IFN gamma   1.8       Two Way MLR 3 day   0.0   HPAEC none   0.0       Two Way MLR 5 day   0.0   HPAEC TNF alpha + IL-   0.0               1beta       Two Way MLR 7 day   0.0   Lung fibroblast none   0.0       PBMC rest   0.0   Lung fibroblast TNF   0.0               alpha + IL-1beta       PBMC PWM   0.0   Lung fibroblast IL-4   1.1       PBMC PHA-L   0.0   Lung fibroblast IL-9   0.0       Ramos (B cell) none   0.0   Lung fibroblast IL-13   2.6       Ramos (B cell)   0.0   Lung fibroblast IFN   1.7       ionomycin       gamma       B lymphocytes PWM   0.0   Dermal fibroblast   1.5               CCD1070 rest       B lymphocytes CD40L   0.0   Dermal fibroblast   0.0       and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast   4.0               CCD1070 IL-1beta       EOL-1 dbcAMP   0.0   Dermal fibroblast IFN   0.0       PMA/ionomycin       gamma       Dendritic cells none   0.0   Dermal fibroblast IL-4   0.0       Dendritic cells LPS   0.0   Dermal Fibroblasts rest   0.0       Dendritic cells anti-   0.0   Neutrophils TNFa + LPS   0.0       CD40       Monocytes rest   0.0   Neutrophils rest   0.0       Monocytes LPS   2.7   Colon   0.0       Macrophages rest   0.0   Lung   2.5       Macrophages LPS   0.0   Thymus   13.3       HUVEC none   1.2   Kidney   100.0       HUVEC starved   0.0                    
     [0625] Panel 4.1D Summary: Ag4206 Highest expression of the CG101201-01 gene is detected in kidney (CT=30.76). Therefore, expression of this gene may be used to distinguish kidney from other samples used in this panel. Furthermore, therapeutic modulation of this gene may be beneficial in the treatment of autoimmune and inflammatory diseases that affect kidney including lupus and glomerulonephritis.  
     [0626] In addition, moderate to low levels of expression of this gene is also seen in thymus, NCI-H292, small airway epithelium and keratinocytes. Therefore, therapeutic modulation of this gene may be useful in the treatment of autoimmune and inflammatory diseases including chronic obstructive pulmonary disease, asthma, allergy, emphysema, psoriasis and wound healing.  
     [0627] This gene codes for homolog of adenine nucleotide translocator (ANT 2). Dysfunctioning of the ANT2 have been shown to induce myopathies in mouse and in humans (Fiore et al., 2001, Clin Chim Acta 311(2):125-35, PMID: 11566172). Therefore, based on homology dysfunctioning of the ANT2 homolog encoded by this gene may also contribute to myopathies in human and therapeutic modulation of this gene or its product may be useful in the treatment of this disease.  
     D. CG101211-01: Novel Protein containing the Mitochondrial Energy Transfer Protein Domain  
     [0628] Expression of gene CG 101211-01 was assessed using the primer-probe set Ag4207, described in Table DA. Results of the RTQ-PCR runs are shown in Tables DB, DC, DD and DE.  
               TABLE DA                          Probe Name Ag4207                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ctgagaaaatggcatctgaaag-3′   22   3681   98               Probe   TET-5′-tgaaacacctactggagctatttcaca-3′-TAMRA   27   3703   99               Reverse   5′-tgacagaaggcatcctttctt-3′   21   3735   100                  
 
     [0629]               TABLE DB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4207, Run       Ag4207, Run       Tissue Name   215601929   Tissue Name   215601929                                     AD 1 Hippo   13.5   Control (Path) 3   5.5               Temporal Ctx       AD 2 Hippo   24.0   Control (Path) 4   30.1               Temporal Ctx       AD 3 Hippo   7.2   AD 1 Occipital Ctx   14.5       AD 4 Hippo   6.0   AD 2 Occipital Ctx   0.1               (Missing)       AD 5 hippo   43.2   AD 3 Occipital Ctx   9.2       AD 6 Hippo   46.3   AD 4 Occipital Ctx   13.2       Control 2 Hippo   25.2   AD 5 Occipital Ctx   11.5       Control 4 Hippo   8.4   AD 6 Occipital Ctx   100.0       Control (Path) 3 Hippo   9.4   Control 1 Occipital Ctx   5.7       AD 1 Temporal Ctx   17.3   Control 2 Occipital Ctx   63.3       AD 2 Temporal Ctx   32.5   Control 3 Occipital Ctx   13.1       AD 3 Temporal Ctx   6.3   Control 4 Occipital Ctx   6.4       AD 4 Temporal Ctx   17.6   Control (Path) 1   92.7               Occipital Ctx       AD 5 Inf Temporal Ctx   36.1   Control (Path) 2   8.5               Occipital Ctx       AD 5 Sup Temporal Ctx   19.1   Control (Path) 3   4.5               Occipital Ctx       AD 6 Inf Temporal Ctx   51.1   Control (Path) 4   13.1               Occipital Ctx       AD 6 Sup Temporal Ctx   48.6   Control 1 Parietal Ctx   8.0       Control 1 Temporal Ctx   3.6   Control 2 Parietal Ctx   22.4       Control 2 Temporal Ctx   40.9   Control 3 Parietal Ctx   16.2       Control 3 Temporal Ctx   9.9   Control (Path) 1 Parietal   85.9               Ctx       Control 4 Temporal Ctx   8.6   Control (Path) 2 Parietal   18.0               Ctx       Control (Path) 1 Temporal   51.4   Control (Path) 3 Parietal   5.8       Ctx       Ctx       Control (Path) 2 Temporal   24.1   Control (Path) 4 Parietal   36.1       Ctx       Ctx                    
     [0630]               TABLE DC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4207,       Ag4207, Run       Tissue Name   Run 221254779   Tissue Name   221254779                                     Adipose   15.4   Renal ca.TK-10   35.6       Melanoma* Hs688(A).T   28.7   Bladder   24.3       Melanoma* Hs688(B).T   22.5   Gastric ca. (liver met.)   90.1               NCI-N87       Melanoma* M14   12.2   Gastric ca. KATO III   33.9       Melanoma* LOXIMVI   19.2   Colon ca. SW-948   2.0       Melanoma* SK-MEL-5   35.6   Colon ca. SW480   24.1       Squamous cell carcinoma   20.3   Colon ca.* (SW480 met)   9.9       SCC-4       SW620       Testis Pool   27.5   Colon ca. HT29   11.9       Prostate ca.* (bone met)   43.2   Colon ca. HCT-116   4.3       PC-3       Prostate Pool   16.2   Colon ca. CaCo-2   11.7       Placenta   0.7   Colon cancer tissue   11.6       Uterus Pool   11.0   Colon ca. SW1116   5.3       Ovarian ca. OVCAR-3   41.8   Colon ca. Colo-205   2.7       Ovarian ca. SK-OV-3   42.3   Colon ca. SW-48   1.9       Ovarian ca. OVCAR-4   5.5   Colon Pool   39.2       Ovarian ca. OVCAR-5   74.7   Small Intestine Pool   32.8       Ovarian ca. IGROV-1   21.0   Stomach Pool   20.4       Ovarian ca. OVCAR-8   20.6   Bone Marrow Pool   10.3       Ovary   24.8   Fetal Heart   24.7       Breast ca. MCF-7   67.4   Heart Pool   17.8       Breast ca. MDA-MB-231   36.3   Lymph Node Pool   36.3       Breast ca. BT 549   83.5   Fetal Skeletal Muscle   15.8       Breast ca. T47D   100.0   Skeletal Muscle Pool   22.5       Breast ca. MDA-N   11.3   Spleen Pool   17.6       Breast Pool   43.5   Thymus Pool   31.6       Trachea   22.1   CNS cancer (glio/astro)   34.2               U87-MG       Lung   9.9   CNS cancer (glio/astro)   44.8               U-118-MG       Fetal Lung   65.1   CNS cancer (neuro; met)   49.3               SK-N-AS       Lung ca. NCI-N417   4.7   CNS cancer (astro) SF-   16.3               539       Lung ca. LX-1   8.3   CNS cancer (astro)   79.6               SNB-75       Lung ca. NCI-H146   6.9   CNS cancer (glio) SNB-   14.0               19       Lung ca. SHP-77   40.9   CNS cancer (glio) SF-   70.2               295       Lung ca. A549   39.2   Brain (Amygdala) Pool   42.0       Lung ca. NCI-H526   7.5   Brain (cerebellum)   49.7       Lung ca. NCI-H23   48.0   Brain (fetal)   51.4       Lung ca. NCI-H460   28.3   Brain (Hippocampus)   44.1               Pool       Lung ca. HOP-62   22.7   Cerebral Cortex Pool   53.6       Lung ca. NCI-H522   17.2   Brain (Substantia nigra)   33.7               Pool       Liver   0.9   Brain (Thalamus) Pool   78.5       Fetal Liver   20.9   Brain (whole)   25.7       Liver ca. HepG2   15.6   Spinal Cord Pool   28.7       Kidney Pool   66.9   Adrenal Gland   6.1       Fetal Kidney   55.1   Pituitary gland Pool   10.7       Renal ca. 786-0   13.5   Salivary Gland   1.9       Renal ca. A498   9.0   Thyroid (female)   25.9       Renal ca. ACHN   17.9   Pancreatic ca. CAPAN2   29.7       Renal ca. UO-31   12.4   Pancreas Pool   36.6                    
     [0631]               TABLE DD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4207, Run       Ag4207, Run       Tissue Name   175226748   Tissue Name   175226748                                     Secondary Th1 act   35.8   HUVEC IL-1beta   38.4       Secondary Th2 act   44.1   HUVEC IFN gamma   45.4       Secondary Tr1 act   28.5   HUVEC TNF alpha +   18.4               IFN gamma       Secondary Th1 rest   18.2   HUVEC TNF alpha +   39.8               IL4       Secondary Th2 rest   17.7   HUVEC IL-11   27.9       Secondary Tr1 rest   24.7   Lung Microvascular EC   66.9               none       Primary Th1 act   11.8   Lung Microvascular EC   47.3               TNF alpha + IL-1beta       Primary Th2 act   24.8   Microvascular Dermal   48.3               EC none       Primary Tr1 act   17.6   Microsvasular Dermal   28.9               EC TNF alpha + IL-1beta       Primary Th1 rest   12.9   Bronchial epithelium   39.5               TNF alpha + IL1beta       Primary Th2 rest   15.7   Small airway epithelium   10.3               none       Primary Tr1 rest   20.3   Small airway epithelium   21.6               TNF alpha + IL-1beta       CD45RA CD4   28.3   Coronery artery SMC   26.6       lymphocyte act       rest       CD45RO CD4   38.2   Coronery artery SMC   22.2       lymphocyte act       TNF alpha + IL-1beta       CD8 lymphocyte act   17.3   Astrocytes rest   22.2       Secondary CD8   26.1   Astrocytes TNF alpha +   21.2       lymphocyte rest       IL-1beta       Secondary CD8   6.1   KU-812 (Basophil) rest   42.0       lymphocyte act       CD4 lymphocyte none   7.0   KU-812 (Basophil)   82.9               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   45.7   CCD1106   43.5       CD95 CH11       (Keratinocytes) none       LAK cells rest   24.1   CCD1106   19.8               (Keratinocytes)               TNF alpha + IL-1beta       LAK cells IL-2   31.0   Liver cirrhosis   12.5       LAK cells IL-2 + IL-12   18.6   NCI-H292 none   32.3       LAK cells IL-2 + IFN   16.7   NCI-H292 IL-4   46.7       gamma       LAK cells IL-2 + IL-18   21.8   NCI-H292 IL-9   100.0       LAK cells   25.2   NCI-H292 IL-13   73.2       PMA/ionomycin       NK Cells IL-2 rest   29.7   NCI-H292 IFN gamma   47.3       Two Way MLR 3 day   32.5   HPAEC none   30.4       Two Way MLR 5 day   22.5   HPAEC TNF alpha +   56.6               IL-1beta       Two Way MLR 7 day   15.8   Lung fibroblast none   49.3       PBMC rest   4.8   Lung fibroblast TNF   40.6               alpha + IL-1beta       PBMC PWM   15.8   Lung fibroblast IL-4   34.9       PBMC PHA-L   17.6   Lung fibroblast IL-9   61.1       Ramos (B cell) none   34.4   Lung fibroblast IL-13   39.2       Ramos (B cell) ionomycin   42.9   Lung fibroblast IFN   35.4               gamma       B lymphocytes PWM   18.2   Dermal fibroblast   34.9               CCD1070 rest       B lymphocytes CD40L   45.7   Dermal fibroblast   47.3       and IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   11.7   Dermal fibroblast   25.3               CCD1070 IL-1beta       EOL-1 dbcAMP   15.2   Dermal fibroblast IFN   39.2       PMA/ionomycin       gamma       Dendritic cells none   38.4   Dermal fibroblast IL-4   67.4       Dendritic cells LPS   25.9   Dermal fibroblasts rest   45.4       Dendritic cells anti-CD40   39.8   Neutrophils TNFa + LPS   7.7       Monocytes rest   20.4   Neutrophils rest   5.7       Monocytes LPS   52.5   Colon   15.3       Macrophages rest   28.5   Lung   32.5       Macrophages LPS   14.2   Thymus   76.3       HUVEC none   27.4   Kidney   62.4       HUVEC starved   23.8                    
     [0632]               TABLE DE                          general oncology screening panel_v_2.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4207, Run       Ag4207, Run       Tissue Name   268624900   Tissue Name   268624900                                     Colon cancer 1   14.5   Bladder cancer NAT 2   1.6       Colon cancer NAT 1   7.3   Bladder cancer NAT 3   0.4       Colon cancer 2   12.4   Bladder cancer NAT 4   5.2       Colon cancer NAT 2   7.1   Adenocarcinoma of the   52.9               prostate 1       Colon cancer 3   17.0   Adenocarcinoma of the   3.3               prostate 2       Colon cancer NAT 3   22.7   Adenocarcinoma of the   14.2               prostate 3       Colon malignant cancer 4   42.9   Adenocarcinoma of the   10.4               prostate 4       Colon normal adjacent   5.6   Prostate cancer NAT 5   4.5       tissue 4       Lung cancer 1   13.7   Adenocarcinoma of the   4.4               prostate 6       Lung NAT 1   2.9   Adenocarcinoma of the   6.6               prostate 7       Lung cancer 2   34.4   Adenocarcinoma of the   2.0               prostate 8       Lung NAT 2   3.2   Adenocarcinoma of the   27.7               prostate 9       Squamous cell carcinoma 3   31.6   Prostate cancer NAT 10   1.5       Lung NAT 3   0.4   kidney cancer 1   16.5       metastatic melanoma 1   44.8   KidneyNAT 1   10.3       Melanoma 2   0.9   Kidney cancer 2   100.0       Melanoma 3   4.8   Kidney NAT 2   28.5       metastatic melanoma 4   80.7   Kidney cancer 3   28.9       metastatic melanoma 5   97.9   Kidney NAT 3   10.4       Bladder cancer 1   3.3   Kidney cancer 4   15.2       Bladder cancer NAT 1   0.0   Kidney NAT 4   10.4       Bladder cancer 2   9.9                    
     [0633] CNS_neurodegeneration_v1.0 Summary: Ag4207 This panel confirms the expression of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.  
     [0634] General_screening_panel_v1.4 Summary: Ag4207 Highest expression of this gene is seen in a breast cancer cell line (CT=27.1). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancers. In addition, this gene is expressed at much higher levels in fetal lung and liver tissue (CTs=28-29) when compared to expression in the adult counterpart (CTs=30-33). Thus, expression of this gene may be used to differentiate between the fetal and adult source of these tissues. This expression profile suggests a role for this gene product in cell survival and proliferation. Therefore, modulation of this gene product may be useful in the treatment of cancer.  
     [0635] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0636] This gene is also expressed at high to moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0637] Panel 4.1D Summary: Ag4207 Highest expression of this gene is seen in IL-9 treated NCI-H292 cells, pulmonary mucoepidermoid cell line (CT=30.1). This gene is expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     [0638] General oncology screening panel_v — 2.4 Summary: Ag4207 Highest expression of this gene is seen in kidney cancer (CT=29.4). In addition, this gene is more highly expressed in lung and kidney cancer than in the corresponding normal adjacent tissue, with moderate levels of expression also seen in melanoma, prostate, and squamous cell cancers. Thus, expression of this gene could be used as a marker of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of lung and kidney cancer.  
     E. CG101904-01: Cytosolic Phosphoprotein-like Proteins  
     [0639] Expression of gene CG101904-01 was assessed using the primer-probe set Ag4227, described in Table EA. Results of the RTQ-PCR runs are shown in Table EB.  
               TABLE EA                          Probe Name Ag4227                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-atagtgcattggtggacaagac-3′   22   1256   101               Probe   TET-5′-agacaatgaaaacccctaagggcctg-3′-TAMRA   26   1289   102               Reverse   5′-caattcccatgatttctccttt-3′   22   1323   103                  
 
     [0640]               TABLE EB                          General_screening panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4227, Run       Ag4227, Run       Tissue Name   221297231   Tissue Name   221297231                                     Adipose   0.0   Renal ca. TK-10   2.6       Melanoma* Hs688(A).T   1.6   Bladder   1.4       Melanoma* Hs688(B).T   4.1   Gastric ca. (liver met.) NCI-   0.0               N87       Melanoma* M14   0.0   Gastric ca. KATO III   0.0       Melanoma* LOXIMVI   1.3   Colon ca. SW-948   0.0       Melanoma* SK-MEL-5   1.9   Colon ca. SW480   2.8       Squamous cell carcinoma   0.0   Colon ca.* (SW480 met)   0.0       SCC-4       SW620       Testis Pool   100.0   Colon ca. HT29   0.0       Prostate ca.* (bone met)   2.2   Colon ca. HCT-116   1.1       PC-3       Prostate Pool   0.0   Colon ca. CaCo-2   0.0       Placenta   0.0   Colon cancer tissue   0.0       Uterus Pool   0.0   Colon ca. SW1116   0.0       Ovarian ca. OVCAR-3   0.0   Colon ca. Colo-205   0.0       Ovarian ca. SK-OV-3   2.3   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   0.0   Colon Pool   0.0       Ovarian ca. OVCAR-5   4.3   Small Intestine Pool   1.4       Ovarian ca. IGROV-1   0.0   Stomach Pool   0.0       Ovarian ca. OVCAR-8   0.0   Bone Marrow Pool   0.0       Ovary   0.0   Fetal Heart   1.1       Breast ca. MCF-7   0.0   Heart Pool   0.0       Breast ca. MDA-MB-231   1.5   Lymph Node Pool   0.0       Breast ca. BT 549   0.0   Fetal Skeletal Muscle   2.6       Breast ca. T47D   4.7   Skeletal Muscle Pool   0.0       Breast ca. MDA-N   0.0   Spleen Pool   0.0       Breast Pool   0.0   Thymus Pool   2.7       Trachea   22.2   CNS cancer (glio/astro)   0.0               U87-MG       Lung   0.0   CNS cancer (glio/astro) U-   0.0               118-MG       Fetal Lung   44.1   CNS cancer (neuro; met)   5.8               SK-N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro) SF-539   0.0       Lung ca. LX-1   0.0   CNS cancer (astro) SNB-75   0.0       Lung ca. NCI-H146   0.0   CNS cancer (glio) SNB-19   1.3       Lung ca. SHP-77   0.0   CNS cancer (glio) SF-295   5.6       Lung ca. A549   0.0   Brain (Amygdala) Pool   0.0       Lung ca. NCI-H526   0.0   Brain (cerebellum)   0.0       Lung ca. NCI-H23   4.2   Brain (fetal)   1.7       Lung ca. NCI-H460   1.8   Brain (Hippocampus) Pool   1.3       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   2.1       Fetal Liver   0.0   Brain (whole)   0.0       Liver ca. HepG2   0.0   Spinal Cord Pool   2.4       Kidney Pool   0.0   Adrenal Gland   0.0       Fetal Kidney   1.6   Pituitary gland Pool   0.0       Renal ca. 786-0   0.0   Salivary Gland   0.0       Renal ca. A498   0.0   Thyroid (female)   0.0       Renal ca. ACHN   0.0   Pancreatic ca. CAPAN2   0.0       Renal ca. UO-31   0.0   Pancreas Pool   2.5                    
     [0641] General_screening_panel_v1.4 Summary: Ag4227 Expression of this gene is restricted to the testis (CT=33.5) and fetal lung (CT=34.7). Thus, expression of this gene could be used to differentiate between these samples and the other samples on this panel and as a marker of testicular tissue. In addition, therapeutic modulation of the expression or function of this gene may be useful in the treatment of male infertility and hypogonadism.  
     F. CG102092-01: GRP1-Associated Scaffold Protein GRASP  
     [0642] Expression of gene CG102092-01 was assessed using the primer-probe set Ag4231, described in Table FA. Results of the RTQ-PCR runs are shown in Tables FB, FC, FD, FE and FF.  
               TABLE FA                          Probe Name Ag4231                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-atcaattcggaaggcagaac-3′   20   630   104               Probe   TET-5′-cgtctgcagtacctgaagcaaaccct-3′-TAMRA   26   658   105               Reverse   5′-acctgtactctccccacttctc-3′   22   688   106                  
 
     [0643]               TABLE FB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4231, Run       Ag4231, Run       Tissue Name   224078129   Tissue Name   224078129                                     AD 1 Hippo   7.7   Control (Path) 3   7.0               Temporal Ctx       AD 2 Hippo   21.0   Control (Path) 4   30.8               Temporal Ctx       AD 3 Hippo   4.6   AD 1 Occipital Ctx   6.7       AD 4 Hippo   23.0   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   57.4   AD 3 Occipital Ctx   6.7       AD 6 Hippo   27.5   AD 4 Occipital Ctx   26.1       Control 2 Hippo   26.6   AD 5 Occipital Ctx   48.0       Control 4 Hippo   10.2   AD 6 Occipital Ctx   48.0       Control (Path) 3 Hippo   5.6   Control 1 Occipital Ctx   12.9       AD 1 Temporal Ctx   11.8   Control 2 Occipital Ctx   75.3       AD 2 Temporal Ctx   29.1   Control 3 Occipital Ctx   21.3       AD 3 Temporal Ctx   9.5   Control 4 Occipital Ctx   7.5       AD 4 Temporal Ctx   33.4   Control (Path) 1   100.0               Occipital Ctx       AD 5 Inf Temporal Ctx   62.4   Control (Path) 2   14.0               Occipital Ctx       AD 5 Sup Temporal Ctx   27.4   Control (Path) 3   11.6               Occipital Ctx       AD 6 Inf Temporal Ctx   32.1   Control (Path) 4   14.2               Occipital Ctx       AD 6 Sup Temporal Ctx   34.6   Control 1 Parietal Ctx   7.7       Control 1 Temporal Ctx   8.4   Control 2 Parietal Ctx   39.0       Control 2 Temporal Ctx   55.9   Control 3 Parietal Ctx   17.7       Control 3 Temporal Ctx   22.8   Control (Path) 1 Parietal   92.7               Ctx       Control 4 Temporal Ctx   11.4   Control (Path) 2 Parietal   23.0               Ctx       Control (Path) 1 Temporal   87.7   Control (Path) 3 Parietal   12.8       Ctx       Ctx       Control (Path) 2 Temporal   54.0   Control (Path) 4 Parietal   50.3       Ctx       Ctx                    
     [0644]               TABLE FC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4231,       Ag4231, Run       Tissue Name   Run 221994366   Tissue Name   221994366                                     Adipose   48.6   Renal ca. TK-10   1.3       Melanoma* Hs688(A).T   3.3   Bladder   9.3       Melanoma* Hs688(B).T   1.0   Gastric ca. (liver met.)   0.7               NCI-N87       Melanoma* M14   13.4   Gastric ca. KATO III   0.4       Melanoma* LOXIMVI   0.2   Colon ca. SW-948   0.5       Melanoma* SK-MEL-5   15.1   Colon ca. SW480   0.7       Squamous cell carcinoma   0.3   Colon ca.* (SW480 met)   1.1       SCC-4       SW620       Testis Pool   2.5   Colon ca. HT29   0.0       Prostate ca.* (bone met)   0.4   Colon ca. HCT-116   0.7       PC-3       Prostate Pool   6.0   Colon ca. CaCo-2   1.9       Placenta   7.4   Colon cancer tissue   12.8       Uterus Pool   2.9   Colon ca. SW1116   0.2       Ovarian ca. OVCAR-3   0.7   Colon ca. Colo-205   0.3       Ovarian ca. SK-OV-3   3.5   Colon ca. SW-48   0.2       Ovarian ca. OVCAR-4   1.2   Colon Pool   7.4       Ovarian ca. OVCAR-5   0.6   Small Intestine Pool   9.2       Ovarian ca. IGROV-1   4.7   Stomach Pool   5.8       Ovarian ca. OVCAR-8   2.3   Bone Marrow Pool   2.9       Ovary   5.6   Fetal Heart   3.3       Breast ca. MCF-7   0.5   Heart Pool   3.8       Breast ca. MDA-MB-231   0.4   Lymph Node Pool   7.6       Breast ca. BT 549   0.4   Fetal Skeletal Muscle   4.6       Breast ca. T47D   1.7   Skeletal Muscle Pool   8.0       Breast ca. MDA-N   0.4   Spleen Pool   16.0       Breast Pool   10.4   Thymus Pool   5.9       Trachea   5.9   CNS cancer (glio/astro)   2.5               U87-MG       Lung   1.4   CNS cancer (glio/astro)   0.8               U-118-MG       Fetal Lung   69.3   CNS cancer (neuro; met)   15.6               SK-N-AS       Lung ca. NCI-N417   0.1   CNS cancer (astro) SF-   5.5               539       Lung ca. LX-1   0.9   CNS cancer (astro)   4.5               SNB-75       Lung ca. NCI-H146   3.6   CNS cancer (glio) SNB-   4.0               19       Lung ca. SHP-77   5.5   CNS cancer (glio) SF-   1.3               295       Lung ca. A549   0.7   Brain (Amygdala) Pool   14.2       Lung ca. NCI-H526   100.0   Brain (cerebellum)   2.6       Lung ca. NCI-H23   2.8   Brain (fetal)   5.4       Lung ca. NCI-H460   0.4   Brain (Hippocampus)   9.0               Pool       Lung ca. HOP-62   0.2   Cerebral Cortex Pool   16.3       Lung ca. NCI-H522   1.2   Brain (Substantia nigra)   21.6               Pool       Liver   0.6   Brain (Thalamus) Pool   20.3       Fetal Liver   1.9   Brain (whole)   22.7       Liver ca. HepG2   6.3   Spinal Cord Pool   3.0       Kidney Pool   18.2   Adrenal Gland   4.9       Fetal Kidney   6.0   Pituitary gland Pool   0.4       Renal ca. 786-0   0.6   Salivary Gland   0.8       Renal ca. A498   0.2   Thyroid (female)   6.6       Renal ca. ACHN   0.4   Pancreatic ca. CAPAN2   0.4       Renal ca. UO-31   0.2   Pancreas Pool   7.8                    
     [0645]               TABLE FD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4231, Run       Ag4231, Run       Tissue Name   175226629   Tissue Name   175226629                                     Secondary Th1 act   0.1   HUVEC IL-1beta   14.0       Secondary Th2 act   0.4   HUVEC IFN gamma   14.6       Secondary Tr1 act   0.2   HUVEC TNF alpha +   4.0               IFN gamma       Secondary Th1 rest   0.1   HUVEC TNF alpha +   8.8               IL4       Secondary Th2 rest   0.4   HUVEC IL-11   10.2       Secondary Tr1 rest   0.2   Lung Microvascular EC   18.0               none       Primary Th1 act   1.0   Lung Microvascular EC   19.1               TNF alpha + IL-1beta       Primary Th2 act   1.2   Microvascular Dermal   6.9               EC none       Primary Tr1 act   2.2   Microsvasular Dermal   10.1               EC TNF alpha + IL-1beta       Primary Th1 rest   1.2   Bronchial epithelium   0.1               TNF alpha + IL1beta       Primary Th2 rest   1.1   Small airway epithelium   0.0               none       Primary Tr1 rest   0.9   Small airway epithelium   0.0               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   100.0   Coronery artery SMC   1.0       act       rest       CD45RO CD4 lymphocyte   1.6   Coronery artery SMC   1.3       act       TNF alpha + IL-1beta       CD8 lymphocyte act   1.3   Astrocytes rest   0.0       Secondary CD8   1.1   Astrocytes TNF alpha +   0.3       lymphocyte rest       IL-1beta       Secondary CD8   0.2   KU-812 (Basophil) rest   0.4       lymphocyte act       CD4 lymphocyte none   0.6   KU-812 (Basophil)   0.5               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.6   CCD1106   0.1       CD95 CH11       (Keratinocytes) none       LAK cells rest   2.7   CCD1106   0.2               (Keratinocytes)               TNF alpha + IL-1beta       LAK cells IL-2   0.4   Liver cirrhosis   1.8       LAK cells IL-2 + IL-12   0.7   NCI-H292 none   0.1       LAK cells IL-2 + IFN   0.4   NCI-H292 IL-4   0.1       gamma       LAK cells IL-2 + IL-18   0.9   NCI-H292 IL-9   0.2       LAK cells PMA/ionomycin   15.3   NCI-H292 IL-13   0.1       NK Cells IL-2 rest   1.0   NCI-H292 IFN gamma   0.1       Two Way MLR 3 day   0.9   HPAEC none   13.3       Two Way MLR 5 day   1.8   HPAEC TNF alpha +   19.2               IL-1beta       Two Way MLR 7 day   1.7   Lung fibroblast none   2.6       PBMC rest   1.4   Lung fibroblast TNF   0.7               alpha + IL-1beta       PBMC PWM   0.7   Lung fibroblast IL-4   1.9       PBMC PHA-L   1.2   Lung fibroblast IL-9   1.4       Ramos (B cell) none   0.0   Lung fibroblast IL-13   1.5       Ramos (B cell) ionomycin   0.0   Lung fibroblast IFN   1.1               gamma       B lymphocytes PWM   0.6   Dermal fibroblast   0.3               CCD1070 rest       B lymphocytes CD40L and   0.7   Dermal fibroblast   0.3       IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   0.1   Dermal fibroblast   0.2               CCD1070 IL-1beta       EOL-1 dbcAMP   0.3   Dermal fibroblast IFN   1.1       PMA/ionomycin       gamma       Dendritic cells none   0.6   Dermal fibroblast IL-4   1.7       Dendritic cells LPS   3.5   Dermal Fibroblasts rest   2.0       Dendritic cells anti-CD40   1.0   Neutrophils TNFa + LPS   1.0       Monocytes rest   0.6   Neutrophils rest   0.3       Monocytes LPS   2.0   Colon   1.0       Macrophages rest   2.0   Lung   3.9       Macrophages LPS   5.9   Thymus   4.9       HUVEC none   9.6   Kidney   1.9       HUVEC starved   16.7                    
     [0646]               TABLE FE                          Panel CNS_1                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4231,       Ag4231,       Tissue Name   Run 181012262   Tissue Name   Run 181012262                                     BA4 Control   25.2   BA17 PSP   22.5       BA4 Control2   71.2   BA17 PSP2   15.9       BA4 Alzheimer&#39;s2   5.8   Sub Nigra Control   6.0       BA4 Parkinson&#39;s   66.0   Sub Nigra Control2   4.3       BA4 Parkinson&#39;s2   55.1   Sub Nigra Alzheimer&#39;s2   4.9       BA4 Huntington&#39;s   27.7   Sub Nigra Parkinson&#39;s2   12.5       BA4 Huntington&#39;s2   29.7   Sub Nigra Huntington&#39;s   58.2       BA4 PSP   10.3   Sub Nigra Huntington&#39;s2   22.1       BA4 PSP2   14.8   Sub Nigra PSP2   3.0       BA4 Depression   11.7   Sub Nigra Depression   8.2       BA4 Depression2   6.9   Sub Nigra Depression2   7.9       BA7 Control   27.9   Glob Palladus Control   10.2       BA7 Control2   43.8   Glob Palladus Control2   23.7       BA7 Alzheimer&#39;s2   7.7   Glob Palladus   9.9               Alzheimer&#39;s       BA7 Parkinson&#39;s   22.5   Glob Palladus   4.0               Alzheimer&#39;s2       BA7 Parkinson&#39;s2   44.8   Glob Palladus   95.9               Parkinson&#39;s       BA7 Huntington&#39;s   37.9   Glob Palladus   16.5               Parkinson&#39;s2       BA7 Huntington&#39;s2   30.1   Glob Palladus PSP   0.0       BA7 PSP   25.5   Glob Palladus PSP2   3.7       BA7 PSP2   30.6   Glob Palladus   0.7               Depression       BA7 Depression   4.2   Temp Pole Control   18.9       BA9 Control   31.9   Temp Pole Control2   52.1       BA9 Control2   100.0   Temp Pole Alzheimer&#39;s   7.3       BA9 Alzheimer&#39;s   7.3   Temp Pole Alzheimer&#39;s2   7.9       BA9 Alzheimer&#39;s2   19.9   Temp Pole Parkinson&#39;s   42.3       BA9 Parkinson&#39;s   33.9   Temp Pole Parkinson&#39;s2   50.0       BA9 Parkinson&#39;s2   59.0   Temp Pole Huntington&#39;s   43.8       BA9 Huntington&#39;s   64.6   Temp Pole PSP   1.4       BA9 Huntington&#39;s2   22.1   Temp Pole PSP2   14.0       BA9 PSP   5.1   Temp Pole Depression2   13.1       BA9 PSP2   0.6   Cing Gyr Control   52.5       BA9 Depression   12.1   Cing Gyr Control2   57.4       BA9 Depression2   16.8   Cing Gyr Alzheimer&#39;s   31.2       BA17 Control   23.8   Cing Gyr Alzheimer&#39;s2   14.1       BA17 Control2   34.2   Cing Gyr Parkinson&#39;s   22.5       BA17 Alzheimer&#39;s2   11.0   Cing Gyr Parkinson&#39;s2   26.1       BA17 Parkinson&#39;s   28.7   Cing Gyr Huntington&#39;s   60.7       BA17 Parkinson&#39;s2   39.5   Cing Gyr Huntington&#39;s2   14.6       BA17 Huntington&#39;s   57.8   Cing Gyr PSP   8.5       BA17 Huntington&#39;s2   27.5   Cing Gyr PSP2   5.3       BA17 Depression   12.5   Cing Gyr Depression   9.8       BA17 Depression2   24.8   Cing Gyr Depression2   7.3                    
     [0647]               TABLE FF                          general oncology screening panel_v_2.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4231, Run       Ag4231, Run       Tissue Name   268624976   Tissue Name   268624976                                     Colon cancer 1   15.0   Bladder cancer NAT 2   0.0       Colon NAT 1   12.8   Bladder cancer NAT 3   0.5       Colon cancer 2   4.4   Bladder cancer NAT 4   7.0       Colon cancer NAT 2   5.1   Adenocarcinoma of the   13.8               prostate 1       Colon cancer 3   12.6   Adenocarcinoma of the   8.4               prostate 2       Colon cancer NAT 3   11.6   Adenocarcinoma of the   8.4               prostate 3       Colon malignant cancer 4   15.3   Adenocarcinoma of the   6.4               prostate 4       Colon normal adjacent   2.3   Prostate cancer NAT 5   5.0       tissue 4       Lung cancer 1   13.7   Adenocarcinoma of the   3.3               prostate 6       Lung NAT 1   5.3   Adenocarcinoma of the   6.2               prostate 7       Lung cancer 2   39.0   Adenocarcinoma of the   0.9               prostate 8       Lung NAT 2   15.7   Adenocarcinoma of the   18.0               prostate 9       Squamous cell carcinoma 3   28.9   Prostate cancer NAT 10   2.3       Lung NAT 3   5.2   Kidney cancer 1   63.3       metastatic melanoma 1   40.1   KidneyNAT 1   22.7       Melanoma 2   9.9   Kidney cancer 2   100.0       Melanoma 3   3.5   Kidney NAT 2   21.3       metastatic melanoma 4   25.9   Kidney cancer 3   26.6       metastatic melanoma 5   29.5   Kidney NAT 3   12.8       Bladder cancer 1   0.7   Kidney cancer 4   49.0       Bladder cancer NAT 1   0.0   Kidney NAT 4   26.6       Bladder cancer 2   1.1                    
     [0648] CNS_neurodegeneration_v1.0 Summary: Ag4231 This panel confirms the expression of the CG102092-01 gene at significant levels in the brain in an independent group of individuals. This gene is found to be down-regulated in the temporal cortex of Alzheimer&#39;s disease patients when analyzed by ANCOVA (P=0.04). Treatment with agonists or antagonists may therefore prevent or delay the onset of AD.  
     [0649] General_screening_panel_v1.4 Summary: Ag4231 Highest expression of the CG102092-01 gene is detected in lung cancer NCI-H526 cell line (CT=25). Significant expression of this gene is also seen in cluster of cancer cell lines derived from gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.  
     [0650] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. This gene codes for a homolog of mouse GRP1-associated scaffold protein GRASP, also known as tamalin. GRASP links a protein complex formation of group 1 metabotropic glutamate receptors (mGluRs) and the guanine nucleotide exchange factor, cytohesins. In addition, it contributes to intracellular trafficking and the macromolecular organization of group 1 mGluRs at synapses (Kitano et al., 2002, J Neurosci 22(4):1280-9, PMID: 11850456; Nevrivy et al., 2000, J Biol Chem 275(22):16827-36, PMID: 10828067). Group I mGluRs are involved in many CNS functions and may participate in a variety of disorders such as pain, epilepsy, ischemia, and chronic neurodegenerative diseases (Bordi F, Ugolini A., 1999, Prog Neurobiol 59(1):55-79, PMID: 10416961). Therefore, therapeutic modulation of this gene product may be useful in the treatment of neurological disorders such as Alzheimer&#39;s disease, Parkinson&#39;s disease, epilepsy, multiple sclerosis, schizophrenia, pain, ischemia and depression.  
     [0651] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.  
     [0652] Panel 4.1D Summary: Ag4231 Highest expression of the CG102092-01 gene is detected in activated CD45RA CD4 lymphocyte (CT=26.8). This gene is expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as lung fibroblast cell types and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.5 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     [0653] Panel CNS — 1 Summary: Ag4231 This panel confirms the expression of the CG102092-01 gene at significant levels in the brain in an independent group of individuals. Please see Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.  
     [0654] General oncology screening panel_v — 2.4 Summary: Ag4231 Highest expression of the CG102092-01 gene is detected in kidney cancer sample (CT=30.3). Significant levels of expression of this gene is also seen in both normal and cancer samples derived from colon, lung, melanoma, prostate, and kidney. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, lung, prostate, melanoma and kidney cancers.  
     G. CG102595-01: neurabin-I (Neural Tissue-specific F-actin Binding Protein I)  
     [0655] Expression of gene CG102595-01 was assessed using the primer-probe set Ag4239, described in Table GA. Results of the RTQ-PCR runs are shown in Tables GB, GC, GD, GE and GF.  
               TABLE GA                          Probe Name Ag4239                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-caagcgaggtgttgatacaga-3′   21   846   107               Probe   TET-5′-tgcaactccagtaccagaagtggctt-3′-TAMRA   26   885   108               Reverse   5′-ttcaccaggtatcgaagctaga-3′   22   924   109                  
 
     [0656]               TABLE GB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4239, Run       Ag4239, Run       Tissue Name   224076987   Tissue Name   224076987                                     AD 1 Hippo   18.9   Control (Path) 3 Temporal   4.2               Ctx       AD 2 Hippo   27.2   Control (Path) 4 Temporal   32.1               Ctx       AD 3 Hippo   5.3   AD 1 Occipital Ctx   22.4       AD 4 Hippo   8.3   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   95.3   AD 3 Occipital Ctx   6.1       AD 6 Hippo   46.0   AD 4 Occipital Ctx   22.4       Control 2 Hippo   32.3   AD 5 Occipital Ctx   47.3       Control 4 Hippo   13.4   AD 6 Occipital Ctx   26.1       Control (Path) 3 Hippo   6.7   Control 1 Occipital Ctx   2.3       AD 1 Temporal Ctx   15.4   Control 2 Occipital Ctx   67.8       AD 2 Temporal Ctx   31.2   Control 3 Occipital Ctx   19.8       AD 3 Temporal Ctx   7.0   Control 4 Occipital Ctx   6.7       AD 4 Temporal Ctx   25.5   Control (Path) 1 Occipital   93.3               Ctx       AD 5 Inf Temporal Ctx   100.0   Control (Path) 2 Occipital   17.3               Ctx       AD 5 Sup Temporal Ctx   46.0   Control (Path) 3 Occipital   2.0               Ctx       AD 6 Inf Temporal Ctx   46.3   Control (Path) 4 Occipital   17.0               Ctx       AD 6 Sup Temporal Ctx   45.7   Control 1 Parietal Ctx   6.7       Control 1 Temporal Ctx   5.4   Control 2 Parietal Ctx   44.4       Control 2 Temporal Ctx   41.8   Control 3 Parietal Ctx   24.5       Control 3 Temporal Ctx   15.5   Control (Path) 1 Parietal   84.1               Ctx       Control 3 Temporal Ctx   11.5   Control (Path) 2 Parietal   25.5               Ctx       Control (Path) 1 Temporal   58.6   Control (Path) 3 Parietal   3.1       Ctx       Ctx       Control (Path) 2 Temporal   36.6   Control (Path) 4 Parietal   46.7       Ctx       Ctx                    
     [0657]               TABLE GC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4239, Run       Ag4239, Run       Tissue Name   222026936   Tissue Name   222026936                                     Adipose   8.7   Renal ca. TK-10   76.8       Melanoma* Hs688(A).T   0.0   Bladder   42.9       Melanoma* Hs688(B).T   0.0   Gastric ca. (liver met.) NCI-   0.2               N87       Melanoma* M14   0.0   Gastric ca. KATO III   0.0       Melanoma* LOXIMVI   2.2   Colon ca. SW-948   11.5       Melanoma* SK-MEL-5   48.6   Colon ca. SW480   71.2       Squamous cell carcinoma   0.0   Colon ca.* (SW480 met)   24.7       SCC-4       SW620       Testis Pool   23.8   Colon ca. HT29   15.0       Prostate ca.* (bone met)   65.5   Colon ca. HCT-116   44.1       PC-3       Prostate Pool   13.2   Colon ca. CaCo-2   100.0       Placenta   3.8   Colon cancer tissue   2.0       Uterus Pool   7.9   Colon ca. SW1116   8.9       Ovarian ca. OVCAR-3   50.3   Colon ca. Colo-205   0.1       Ovarian ca. SK-OV-3   35.4   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   28.5   Colon Pool   13.2       Ovarian ca. OVCAR-5   49.0   Small Intestine Pool   23.7       Ovarian ca. IGROV-1   47.0   Stomach Pool   24.0       Ovarian ca. OVCAR-8   11.0   Bone Marrow Pool   5.9       Ovary   15.7   Fetal Heart   36.6       Breast ca. MCF-7   7.1   Heart Pool   9.0       Breast ca. MDA-MB-231   7.2   Lymph Node Pool   27.4       Breast ca. BT 549   66.0   Fetal Skeletal Muscle   29.3       Breast ca. T47D   63.3   Skeletal Muscle Pool   22.7       Breast ca. MDA-N   0.1   Spleen Pool   25.3       Breast Pool   19.6   Thymus pool   13.5       Trachea   29.5   CNS cancer (glio/astro)   2.2               U87-MG       Lung   11.2   CNS cancer (glio/astro) U-   0.1               118-MG       Fetal Lung   77.9   CNS cancer (neuro; met)   20.9               SK-N-AS       Lung ca. NCI-N417   2.5   CNS cancer (astro) SF-539   0.7       Lung ca. LX-1   55.5   CNS cancer (astro) SNB-75   1.0       Lung ca. NCI-H146   6.7   CNS cancer (glio) SNB-19   57.4       Lung ca. SHP-77   28.3   CNS cancer (glio) SF-295   4.3       Lung ca. A549   74.2   Brain (Amygdala) Pool   40.1       Lung ca. NCI-H526   9.0   Brain (cerebellum)   23.0       Lung ca. NCI-H23   53.6   Brain (fetal)   73.2       Lung ca. NCI-H460   14.7   Brain (Hippocampus) Pool   40.6       Lung ca. HOP-62   7.4   Cerebral Cortex Pool   80.7       Lung ca. NCI-H522   11.0   Brain (Substantia nigra)   53.2               Pool       Liver   0.0   Brain (Thalamus) Pool   75.3       Fetal Liver   17.2   Brain (whole)   38.7       Liver ca. HepG2   51.1   Spinal Cord Pool   28.9       Kidney Pool   32.1   Adrenal Gland   28.5       Fetal Kidney   84.1   Pituitary gland Pool   16.7       Renal ca. 786-0   43.2   Salivary Gland   14.3       Renal ca. A498   14.2   Thyroid (female)   9.3       Renal ca. ACHN   9.9   Pancreatic ca. CAPAN2   45.1       Renal ca. UO-31   55.5   Pancreas Pool   36.3                    
     [0658]               TABLE GD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4239, Run       Ag4239, Run       Tissue Name   175226819   Tissue Name   175226819                                     Secondary Th1 act   1.2   HUVEC IL-1beta   9.9       Secondary Th2 act   0.4   HUVEC IFN gamma   11.3       Secondary Tr1 act   0.0   HUVEC TNF alpha + IFN   3.0               gamma       Secondary Th1 rest   0.2   HUVEC TNF alpha + IL4   5.5       Secondary Th2 rest   0.0   HUVEC IL-11   9.7       Secondary Tr1 rest   0.3   Lung Microvascular EC   3.9               none       Primary Th1 act   0.8   Lung Microvascular EC   0.4               TNF alpha + IL-1beta       Primary Th2 act   0.0   Microvascular Dermal EC   5.0               none       Primary Tr1 act   0.0   Microsvasular Dermal EC   1.6               TNF alpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   0.0               TNF alpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium   0.6               none       Primary Tr1 rest   0.0   Small airway epithelium   0.0               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   2.0   Coronery artery SMC rest   0.0       act       CD45RO CD4 lymphocyte   0.0   Coronery artery SMC   0.9       act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.3   Astrocytes rest   22.2       Secondary CD8 lymphocyte   0.0   Astrocytes TNF alpha + IL-   19.5       rest       1beta       Secondary CD8 lymphocyte   0.0   KU-812 (Basophil) rest   7.3       act       CD4 lymphocyte none   0.5   KU-812 (Basophil)   9.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.0   CCD1106 (Keratinocytes)   0.0       CD95 CH11       none       LAK cells rest   4.0   CCD1106 (Keratinocytes)   0.0               TNF alpha + IL-1beta       LAK cells IL-2   2.5   Liver cirrhosis   13.3       LAK cells IL-2 + IL-12   1.8   NCI-H292 none   13.1       LAK cells IL-2 + IFN   1.7   NCI-H292 IL-4   21.6       gamma       LAK cells IL-2 + IL-18   2.1   NCI-H292 IL-9   24.0       LAK cells PMA/ionomycin   1.7   NCI-H292 IL-13   24.0       NK Cells IL-2 rest   18.0   NCI-H292 IFN gamma   19.2       Two Way MLR 3 day   1.2   HPAEC none   14.2       Two Way MLR 5 day   0.4   HPAEC TNF alpha + IL-1   15.7               beta       Two Way MLR 7 day   0.0   Lung fibroblast none   6.6       PBMC rest   0.5   Lung fibroblast TNF alpha +   3.5               IL-1beta       PBMC PWM   3.2   Lung fibroblast IL-4   4.6       PBMC PHA-L   0.7   Lung fibroblast IL-9   9.2       Ramos (B cell) none   0.0   Lung fibroblast IL-13   5.8       Ramos (B cell) ionomycin   0.0   Lung fibroblast IFN gamma   5.7       B lymphocytes PWM   3.2   Dermal fibroblast CCD1070   3.5               rest       B lymphocytes CD40L and   2.1   Dermal fibroblast CCD1070   2.5       IL-4       TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast CCD1070   1.3               IL-1beta       EOL-1 dbcAMP   0.0   Dermal fibroblast IFN   2.2       PMA/ionomycin       gamma       Dendritic cells none   0.9   Dermal fibroblast IL-4   12.9       Dendritic cells LPS   0.5   Dermal Fibroblasts rest   9.7       Dendritic cells anti-CD40   0.0   Neutrophils TNFa + LPS   1.0       Monocytes rest   0.5   Neutrophils rest   2.3       Monocytes LPS   0.0   Colon   15.4       Macrophages rest   1.1   Lung   19.3       Macrophages LPS   0.0   Thymus   12.8       HUVEC none   4.1   Kidney   100.0       HUVEC starved   7.2                    
     [0659]               TABLE GE                          Panel CNS_1                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4239,       Ag4239, Run       Tissue Name   Run 181012675   Tissue Name   181012675                                     BA4 Control   36.6   BA17 PSP   18.4       BA4 Control2   49.7   BA17 PSP2   11.3       BA4 Alzheimer&#39;s2   8.0   Sub Nigra Control   31.6       BA4 Parkinson&#39;s   59.5   Sub Nigra Control2   25.3       BA4 Parkinson&#39;s2   100.0   Sub Nigra Alzheimer&#39;s2   9.0       BA4 Huntington&#39;s   32.3   Sub Nigra Parkinson&#39;s2   43.5       BA4 Huntington&#39;s2   4.4   Sub Nigra Huntington&#39;s   46.0       BA4 PSP   11.5   Sub Nigra Huntington&#39;s2   24.5       BA4 PSP2   29.3   Sub Nigra PSP2   6.8       BA4 Depression   12.6   Sub Nigra Depression   7.5       BA4 Depression2   8.0   Sub Nigra Depression2   4.6       BA7 Control   49.3   Glob Palladus Control   15.5       BA7 Control2   34.6   Glob Palladus Control2   14.0       BA7 Alzheimer&#39;s2   3.6   Glob Palladus Alzheimer&#39;s   8.8       BA7 Parkinson&#39;s   17.6   Glob Palladus Alzheimer&#39;s2   3.8       BA7 Parkinson&#39;s2   54.3   Glob Palladus Parkinson&#39;s   84.1       BA7 Huntington&#39;s   52.1   Glob Palladus Parkinson&#39;s2   18.2       BA7 Huntington&#39;s2   62.0   Glob Palladus PSP   4.7       BA7 PSP   27.4   Glob Palladus PSP2   8.5       BA7 PSP2   28.5   Glob Palladus Depression   5.8       BA7 Depression   9.0   Temp Pole Control   15.8       BA9 Control   27.4   Temp Pole Control2   41.2       BA9 Control2   74.2   Temp Pole Alzheimer&#39;s   6.0       BA9 Alzheimer&#39;s   5.2   Temp Pole Alzheimer&#39;s2   5.3       BA9 Alzheimer&#39;s2   13.1   Temp Pole Parkinson&#39;s   27.7       BA9 Parkinson&#39;s   31.4   Temp Pole Parkinson&#39;s2   29.3       BA9 Parkinson&#39;s2   49.0   Temp Pole Huntington&#39;s   39.5       BA9 Huntington&#39;s   53.2   Temp Pole PSP   2.3       BA9 Huntington&#39;s2   23.7   Temp Pole PSP2   4.6       BA9 PSP   12.0   Temp Pole Depression2   7.3       BA9 PSP2   3.8   Cing Gyr Control   63.3       BA9 Depression   4.7   Cing Gyr Control2   35.4       BA9 Depression2   6.5   Cing Gyr Alzheimer&#39;s   19.9       BA17 Control   64.2   Cing Gyr Alzheimer&#39;s2   9.1       BA17 Control2   47.6   Cing Gyr Parkinson&#39;s   35.6       BA17 Alzheimer&#39;s2   9.9   Cing Gyr Parkinson&#39;s2   37.1       BA17 Parkinson&#39;s   36.3   Cing Gyr Huntington&#39;s   72.2       BA17 Parkinson&#39;s2   57.4   Cing Gyr Huntington&#39;s2   27.5       BA17 Huntington&#39;s   33.9   Cing Gyr PSP   15.8       BA17 Huntington&#39;s2   22.2   Cing Gyr PSP2   4.9       BA17 Depression   8.4   Cing Gyr Depression   7.1       BA17 Depression2   25.5   Cing Gyr Depression2   9.5                    
     [0660]               TABLE GF                          general oncology screening panel_v_2.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4239, Run       Ag4239, Run       Tissue Name   268664315   Tissue Name   268664315                                     Colon cancer 1   5.1   Bladder cancer NAT 2   0.2       Colon NAT 1   6.3   Bladder cancer NAT 3   0.2       Colon cancer 2   8.3   Bladder cancer NAT 4   3.5       Colon cancer NAT 2   4.0   Adenocarcinoma of the   2.2               prostate 1       Colon cancer 3   2.8   Adenocarcinoma of the   1.2               prostate 2       Colon cancer NAT 3   18.4   Adenocarcinoma of the   4.0               prostate 3       Colon malignant cancer 4   17.3   Adenocarcinoma of the   5.8               prostate 4       Colon normal adjacent   3.4   Prostate cancer NAT 5   0.4       tissue 4       Lung cancer 1   23.8   Adenocarcinoma of the   2.5               prostate 6       Lung NAT 1   1.6   Adenocarcinoma of the   2.7               prostate 7       Lung cancer 2   100.0   Adenocarcinoma of the   1.3               prostate 8       Lung NAT 2   2.0   Adenocarcinoma of the   3.8               prostate 9       Squamous cell carcinoma 3   17.3   Prostate cancer NAT 10   1.7       Lung NAT 3   0.8   Kidney cancer 1   8.2       metastatic melanoma 1   14.9   KidneyNAT 1   8.7       Melanoma 2   0.2   Kidney cancer 2   33.7       Melanoma 3   1.2   Kidney NAT 2   20.6       metastatic melanoma 4   22.5   Kidney cancer 3   11.0       metastatic melanoma 5   21.5   Kidney NAT 3   6.9       Bladder cancer 1   0.8   Kidney cancer 4   5.0       Bladder cancer NAT 1   0.0   Kidney NAT 4   4.5       Bladder cancer 2   1.8                    
     [0661] CNS_neurodegeneration_v1.0 Summary: Ag4239 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.  
     [0662] General_screening panel_v1.4 Summary: Ag4239 This gene is widely expressed in this panel, with highest expression in a colon cancer cell line (CT=26.6). High levels of expression are also seen in cell lines derived from brain, renal, prostate, lung, breast, ovarian, and melanoma cancers. In addition, higher levels of expression are seen in fetal liver (CT=29) and lung (CT=26.9) when compared to expression in the adult liver (CT=40) and lung (CT=29.7). Thus, expression of this gene could be used to differentiate between the fetal and adult sources of these tissues. Since cell lines and fetal tissues are generally more proliferative than adult tissue, this expression profile suggests a role for this gene product in cell survival and proliferation. Therefore, modulation of this gene product may be useful in the treatment of cancer.  
     [0663] Among tissues with metabolic function, this gene is expressed at moderate levels in pituitary, adipose, adrenal gland, pancreas, thyroid, fetal liver and adult and fetal skeletal muscle and heart. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0664] This gene is also expressed at high levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. This gene encodes a homolog of neurabin, a neural protein that may be involved in neurite formation. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0665] Panel 4.1D Summary: Ag4239 Highest expression of this gene is seen in kidney (CT=29. 7). In addition, this gene is expressed at low but significant levels in a wide range of cell types of significance in the immune response in health and disease. These cells include LAK and NK cells, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     [0666] Panel CNS — 1 Summary: Ag4239 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.  
     [0667] General oncology screening panel_v — 2.4 Summary: Ag4239 Highest expression of this gene is seen in lung cancer (CT=26.7). In addition, this gene appears to be overexpressed in lung and kidney cancer when compared to expression in normal adjacent tissue. Furthermore, significant expression of this gene is also seen in melanoma, prostate, bladder and colon cancer. Therefore, therapeutic, modulation of this gene product may be useful in the treatment of these cancers.  
     H. CG102744-01: Novel Epidermal Fatty Acid Receptor  
     [0668] Expression of gene CG102744-01 was assessed using the primer-probe set Ag4252, described in Table HA.  
               TABLE HA                          Probe Name Ag4252                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ggactgtgtcatgaaccatgt-3′   21   357   110               Probe   TET-5′-cgcctgtactcggatctatgaaaa-3′-TAMRA   24   378   111               Reverse   5′-ctgtccaaagtgatgatggaa-3′   21   415   112                  
 
     I. CG102801-01: Septin 6-like Protein  
     [0669] Expression of gene CG102801-01 was assessed using the primer-probe set Ag4243, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB, IC, ID, IE and IF.  
               TABLE IA                          Probe Name Ag4243                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-gtagaaacaaaccaacgaccaa-3′   22   3452   113               Probe   TET-5′-tgctcagatactcagccagtagctca-3′-TAMRA   26   496   114               Reverse   5′-agacctgacaggcctaactca-3′   21   3531   115                  
 
     [0670]               TABLE IB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4243, Run       Ag4243, Run       Tissue Name   224077466   Tissue Name   224077466                                     AD 1 Hippo   17.8   Control (Path) 3 Temporal   13.7               Ctx       AD 2 Hippo   29.5   Control (Path) 4 Temporal   38.2               Ctx       AD 3 Hippo   17.7   AD 1 Occipital Ctx   32.1       AD 4 Hippo   6.3   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   100.0   AD 3 Occipital Ctx   15.0       AD 6 Hippo   63.7   AD 4 Occipital Ctx   27.5       Control 2 Hippo   30.6   AD 5 Occipital Ctx   38.4       Control 4 Hippo   21.6   AD 6 Occipital Ctx   28.9       Control (Path) 3 Hippo   20.6   Control 1 Occipital Ctx   21.3       AD 1 Temporal Ctx   32.3   Control 2 Occipital Ctx   50.3       AD 2 Temporal Ctx   35.6   Control 3 Occipital Ctx   28.3       AD 3 Temporal Ctx   14.9   Control 4 Occipital Ctx   6.3       AD 4 Temporal Ctx   33.9   Control (Path) 1 Occipital   79.0               Ctx       AD 5 Inf Temporal Ctx   71.2   Control (Path) 2 Occipital   25.5               Ctx       AD 5 Sup Temporal Ctx   47.0   Control (Path) 3 Occipital   5.1               Ctx       AD 6 Inf Temporal Ctx   71.2   Control (Path) 4 Occipital   36.6               Ctx       AD 6 Sup Temporal Ctx   79.0   Control 1 Parietal Ctx   21.0       Control 1 Temporal Ctx   13.8   Control 2 Parietal Ctx   55.1       Control 2 Temporal Ctx   26.1   Control 3 Parietal Ctx   22.1       Control 3 Temporal Ctx   31.0   Control (Path) 1 Parietal   55.9               Ctx       Control 3 Temporal Ctx   17.1   Control (Path) 2 Parietal   51.4               Ctx       Control (Path) 1 Temporal   55.1   Control (Path) 3 Parietal   12.9       Ctx       Ctx       Control (Path) 2 Temporal   47.6   Control (Path) 4 Parietal   58.2       Ctx       Ctx                    
     [0671]               TABLE IC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4243, Run       Ag4243, Run       Tissue Name   222018642   Tissue Name   222018642                                     Adipose   7.9   Renal ca. TK-10   2.0       Melanoma* Hs688(A).T   14.1   Bladder   7.0       Melanoma* Hs688(B).T   2.1   Gastric ca. (liver met.)   4.5               NCI-N87       Melanoma* M14   26.2   Gastric ca. KATO III   5.2       Melanoma* LOXIMVI   10.7   Colon ca. SW-948   0.7       Melanoma* SK-MEL-5   6.3   Colon ca. SW480   12.2       Squamous cell carcinoma   2.4   Colon ca.* (SW480 met)   23.2       SCC-4       SW620       Testis Pool   22.4   Colon ca. HT29   0.3       Prostate ca.* (bone met)   25.5   Colon ca. HCT-116   4.7       PC-3       Prostate Pool   4.2   Colon ca. CaCo-2   8.1       Placenta   4.4   Colon cancer tissue   3.7       Uterus Pool   3.4   Colon ca. SW1116   0.9       Ovarian ca. OVCAR-3   4.8   Colon ca. Colo-205   0.5       Ovarian ca. SK-OV-3   15.2   Colon ca. SW-48   0.8       Ovarian ca. OVCAR-4   1.9   Colon Pool   9.2       Ovarian ca. OVCAR-5   7.3   Small Intestine Pool   15.4       Ovarian ca. IGROV-1   2.8   Stomach Pool   6.5       Ovarian ca. OVCAR-8   6.3   Bone Marrow Pool   6.0       Ovary   3.5   Fetal Heart   4.5       Breast ca. MCF-7   0.2   Heart Pool   4.4       Breast ca. MDA-MB-231   11.3   Lymph Node Pool   9.5       Breast ca. BT 549   50.7   Fetal Skeletal Muscle   7.1       Breast ca. T47D   11.0   Skeletal Muscle Pool   1.2       Breast ca. MDA-N   13.9   Spleen Pool   23.2       Breast Pool   9.2   Thymus Pool   36.3       Trachea   6.4   CNS cancer (glio/astro)   0.7               U87-MG       Lung   6.9   CNS cancer (glio/astro) U-   1.2               118-MG       Fetal Lung   32.3   CNS cancer (neuro; met)   100.0               SK-N-AS       Lung ca. NCI-N417   3.0   CNS cancer (astro) SF-539   11.0       Lung ca. LX-1   7.5   CNS cancer (astro) SNB-75   15.9       Lung ca. NCI-H146   0.1   CNS cancer (glio) SNB-19   2.8       Lung ca. SHP-77   11.4   CNS cancer (glio) SF-295   21.3       Lung ca. A549   6.1   Brain (Amygdala) Pool   0.6       Lung ca. NCI-H526   1.0   Brain (cerebellum)   4.8       Lung ca. NCI-H23   14.6   Brain (fetal)   3.4       Lung ca. NCI-H460   3.3   Brain (Hippocampus) Pool   1.6       Lung ca. HOP-62   7.3   Cerebral Cortex Pool   1.4       Lung ca. NCI-H522   44.8   Brain (Substantia nigra)   1.0               Pool       Liver   1.2   Brain (Thalamus) Pool   1.5       Fetal Liver   8.2   Brain (whole)   2.0       Liver ca. HepG2   3.8   Spinal Cord Pool   2.1       Kidney Pool   11.3   Adrenal Gland   45.1       Fetal Kidney   40.3   Pituitary gland Pool   1.8       Renal ca. 786-0   2.8   Salivary Gland   2.3       Renal ca. A498   3.7   Thyroid (female)   1.3       Renal ca. ACHN   4.4   Pancreatic ca. CAPAN2   2.4       Renal ca. UO-31   5.4   Pancreas Pool   9.5                    
     [0672]               TABLE ID                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4243, Run       Ag4243, Run       Tissue Name   175165705   Tissue Name   175165705                                     Secondary Th1 act   35.8   HUVEC IL-1beta   8.1       Secondary Th2 act   32.1   HUVEC IFN gamma   17.4       Secondary Tr1 act   30.6   HUVEC TNF alpha + IFN   7.7               gamma       Secondary Th1 rest   22.2   HUVEC TNF alpha + IL4   5.2       Secondary Th2 rest   26.4   HUVEC IL-11   9.7       Secondary Tr1 rest   27.9   Lung Microvascular EC   12.9               none       Primary Th1 act   27.9   Lung Microvascular EC   9.9               TNF alpha + IL-1beta       Primary Th2 act   36.9   Microvascular Dermal EC   15.6               none       Primary Tr1 act   36.3   Microsvasular Dermal EC   11.0               TNF alpha + IL-1beta       Primary Th1 rest   38.4   Bronchial epithelium   1.0               TNF alpha + IL1beta       Primary Th2 rest   55.9   Small airway epithelium   0.7               none       Primary Tr1 rest   99.3   Small airway epithelium   0.9               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   22.5   Coronery artery SMC rest   7.6       act       CD45RO CD4 lymphocyte   61.1   Coronery artery SMC   7.5       act       TNF alpha + IL-1beta       CD8 lymphocyte act   35.1   Astrocytes rest   2.9       Secondary CD8   38.7   Astrocytes TNF alpha + IL-   1.1       lymphocyte rest       1beta       Secondary CD8   24.5   KU-812 (Basophil) rest   6.5       lymphocyte act       CD4 lymphocyte none   31.4   KU-812 (Basophil)   6.1               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   54.0   CCD1106 (Keratinocytes)   1.7       CD95 CH11       none       LAK cells rest   16.3   CCD1106 (Keratinocytes)   3.2               TNF alpha + IL-1beta       LAK cells IL-2   32.5   Liver cirrhosis   5.3       LAK cells IL-2 + IL-12   21.3   NCI-H292 none   5.2       LAK cells IL-2 + IFN   40.1   NCI-H292 IL-4   6.7       gamma       LAK cells IL-2 + IL-18   47.6   NCI-H292 IL-9   8.1       LAK cells PMA/ionomycin   8.4   NCI-H292 IL-13   5.5       NK Cells IL-2 rest   59.5   NCI-H292 IFN gamma   6.2       Two Way MLR 3 day   36.3   HPAEC none   9.9       Two Way MLR 5 day   29.1   HPAEC TNF alpha + IL-1   12.5               beta       Two Way MLR 7 day   40.3   Lung fibroblast none   2.9       PBMC rest   21.9   Lung fibroblast TNF   3.0               alpha + IL-1beta       PBMC PWM   14.5   Lung fibroblast IL-4   2.6       PBMC PHA-L   26.4   Lung fibroblast IL-9   2.4       Ramos (B cell) none   29.3   Lung fibroblast IL-13   3.3       Ramos (B cell) ionomycin   26.8   Lung fibroblast IFN   3.7               gamma       B lymphocytes PWM   25.3   Dermal fibroblast   7.6               CCD1070 rest       B lymphocytes CD40L and   33.2   Dermal fibroblast   50.7       IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   19.6   Dermal fibroblast   3.2               CCD1070 IL-1beta       EOL-1 dbcAMP   8.9   Dermal fibroblast IFN   5.2       PMA/ionomycin       gamma       Dendritic cells none   9.0   Dermal fibroblast IL-4   4.3       Dendritic cells LPS   4.7   Dermal Fibroblasts rest   5.5       Dendritic cells anti-CD40   5.4   Neutrophils TNFa + LPS   2.0       Monocytes rest   7.9   Neutrophils rest   6.5       Monocytes LPS   2.5   Colon   6.0       Macrophages rest   5.2   Lung   6.8       Macrophages LPS   1.8   Thymus   100.0       HUVEC none   7.8   Kidney   21.2       HUVEC starved   8.4                    
     [0673]               TABLE IE                          Panel CNS_1.1                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4243,       Ag4243, Run       Tissue Name   Run 195308641   Tissue Name   195308641                                     Cing Gyr Depression2   62.9   BA17 PSP2   20.7       Cing Gyr Depression   24.5   BA17 PSP   82.4       Cing Gyr PSP2   17.0   BA17 Huntington&#39;s2   35.4       Cing Gyr PSP   57.4   BA17 Huntington&#39;s   40.9       Cing Gyr Huntington&#39;s2   19.3   BA17 Parkinson&#39;s2   45.4       Cing Gyr Huntington&#39;s   93.3   BA17 Parkinson&#39;s   90.1       Cing Gyr Parkinson&#39;s2   40.3   BA17 Alzheimer&#39;s2   60.3       Cing Gyr Parkinson&#39;s   46.0   BA17 Control2   19.3       Cing Gyr Alzheimer&#39;s2   29.1   BA17 Control   57.0       Cing Gyr Alzheimer&#39;s   21.2   BA9 Depression2   41.5       Cing Gyr Control2   11.7   BA9 Depression   15.2       Cing Gyr Control   24.3   BA9 PSP2   23.5       Temp Pole Depression2   13.0   BA9 PSP   30.8       Temp Pole PSP2   0.0   BA9 Huntington&#39;s2   24.0       Temp Pole PSP   20.9   BA9 Huntington&#39;s   48.6       Temp Pole Huntington&#39;s   42.0   BA9 Parkinson&#39;s2   62.9       Temp Pole Parkinson&#39;s2   31.6   BA9 Parkinson&#39;s   48.0       Temp Pole Parkinson&#39;s   57.0   BA9 Alzheimer&#39;s2   11.7       Temp Pole Alzheimer&#39;s2   29.5   BA9 Alzheimer&#39;s   0.0       Temp Pole Alzheimer&#39;s   18.6   BA9 Control2   66.0       Temp Pole Control2   38.2   BA9 Control   11.1       Temp Pole Control   14.9   BA7 Depression   10.0       Glob Palladus Depression   11.9   BA7 PSP2   19.8       Glob Palladus PSP2   0.0   BA7 PSP   78.5       Glob Palladus PSP   6.5   BA7 Huntington&#39;s2   67.8       Glob Palladus Parkinson&#39;s2   14.5   BA7 Huntington&#39;s   39.8       Glob Palladus Parkinson&#39;s   84.7   BA7 Parkinson&#39;s2   27.0       Glob Palladus   18.8   BA7 Parkinson&#39;s   100.0       Alzheimer&#39;s2       Glob Palladus Alzheimer&#39;s   30.4   BA7 Alzheimer&#39;s2   24.0       Glob Palladus Control2   15.5   BA7 Control2   20.4       Glob Palladus Control   6.1   BA7 Control   31.2       Sub Nigra Depression2   20.0   BA4 Depression2   27.2       Sub Nigra Depression   45.7   BA4 Depression   28.7       Sub Nigra PSP2   5.9   BA4 PSP2   26.2       Sub Nigra Huntington&#39;s2   80.7   BA4 PSP   11.4       Sub Nigra Huntington&#39;s   76.8   BA4 Huntington&#39;s2   24.1       Sub Nigra Parkinson&#39;s2   0.0   BA4 Huntington&#39;s   57.0       Sub Nigra Alzheimer&#39;s2   11.1   BA4 Parkinson&#39;s2   82.9       Sub Nigra Control2   33.9   BA4 Parkinson&#39;s   56.6       Sub Nigra Control   55.1   BA4 Alzheimer&#39;s2   27.2       BA17 Depression2   92.0   BA4 Control2   68.3       BA17 Depression   33.0   BA4 Control   18.7                    
     [0674]               TABLE IF                          general oncology screening panel_v_2.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4243, Run       Ag4243, Run       Tissue Name   268664318   Tissue Name   268664318                                     Colon cancer 1   5.3   Bladder cancer NAT 2   1.0       Colon cancer NAT 1   0.0   Bladder cancer NAT 3   0.0       Colon cancer 2   13.4   Bladder cancer NAT 4   6.2       Colon cancer NAT 2   0.0   Adenocarcinoma of the   0.0               prostate 1       Colon cancer 3   31.0   Adenocarcinoma of the   0.0               prostate 2       Colon cancer NAT 3   40.9   Adenocarcinoma of the   4.0               prostate 3       Colon malignant cancer 4   4.2   Adenocarcinoma of the   3.0               prostate 4       Colon normal adjacent   20.6   Prostate cancer NAT 5   3.8       tissue 4       Lung cancer 1   6.7   Adenocarcinoma of the   2.1               prostate 6       Lung NAT 1   0.0   Adenocarcinoma of the   1.9               prostate 7       Lung cancer 2   0.0   Adenocarcinoma of the   5.7               prostate 8       Lung NAT 2   3.2   Adenocarcinoma of the   26.6               prostate 9       Squamous cell carcinoma 3   31.0   Prostate cancer NAT 10   0.0       Lung NAT 3   3.0   Kidney cancer 1   42.6       metastatic melanoma 1   0.1   KidneyNAT 1   13.8       Melanoma 2   0.0   Kidney cancer 2   100.0       Melanoma 3   6.3   Kidney NAT 2   38.2       metastatic melanoma 4   33.7   Kidney cancer 3   9.7       metastatic melanoma 5   24.1   Kidney NAT 3   9.5       Bladder cancer 1   0.0   Kidney cancer 4   1.9       Bladder cancer NAT 1   0.0   Kidney NAT 4   4.6       Bladder cancer 2   6.2                    
     [0675] CNS_neurodegeneration_v1.0 Summary: Ag4243 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.  
     [0676] General_screening_panel_v1.4 Summary: Ag4243 Highest expression of this gene is seen in a brain cancer cell line (CT=25.9). In addition, this gene appears to be more highly expressed in fetal tissues and cancer cell lines, with moderate to high levels of expression in colon, lung, breast, prostate, and melanoma cancer cell lines. Thus, expression of this gene could be used to differentiate the brain cancer cell line from other samples on this panel and as a marker of brain cancer. This expression profile also suggests a role for this gene product in cell survival and proliferation. This gene is homologous to members of the septin family. Septins are a family of conserved GTPases that have been implicated in a variety of cellular functions involving specialized regions of the cell cortex and changes in cell shape (1). Recent work also suggests novel functions for septins in vesicle trafficking, oncogenesis and compartmentalization of the plasma membrane (2). For example, a human septin gene has recently been identified that is commonly deleted in sporadic epithelial ovarian tumors and is therefore a candidate ovarian tumor suppressor gene (3). Given the ability of the septins to bind GTP and phosphatidylinositol 4,5-bisphosphate in a mutually exclusive manner, these proteins might be crucial elements for the spatial and/or temporal control of diverse cellular functions (2). Therefore, modulation of this gene product may be useful in the treatment of cancer.  
     [0677] Among tissues with metabolic function, this gene is expressed at high levels in adrenal, moderate levels in pituitary, adipose, pancreas, fetal liver and skeletal muscle, adult and fetal liver, and low but significant levels in thyroid, liver, and skeletal muscle. Based on its potential effects on signalling and vesicle trafficking, targeting this septin-like gene might also provide a valuable treatment for metabolic diseases, including diabetes and obesity.  
     [0678] This gene is also expressed at moderate to low levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. A septin that is preferentially expressed in the nervous system has been described and is proposed to regulate vesicle dynamics through interactions with syntaxin (4). Furthermore, septins have been found in neurofibrillary tangles in Alzheimer&#39;s disease, suggesting that septins may play a role in neurological diseases (5). Similarly, comparative immunohistochemical analysis of several mouse septins suggests that mouse septin 6 is associated with synaptic vesicles in various brain regions, including glomeruli of the olfactory bulb (6). Based on the homology of this protein to septin and its expression in this panel, this gene product may play a role in the regulation of cytoskeletal function, the assembly of signalling complexes, vesicle trafficking, and compartmentalization of the plasma membrane. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0679] References:  
     [0680] 1. Field C. M., Kellogg D. (1999) Septins: cytoskeletal polymers or signalling GTPases? Trends Cell. Biol. 9: 387-394.  
     [0681] 2. Kartmann B., Roth D. (2001) Novel roles for mammalian septins: from vesicle trafficking to oncogenesis. J. Cell. Sci. 114: 839-844.  
     [0682] 3. Russell S. E., McIlhatton M. A., Burrows J. F., Donaghy P. G., Chanduloy S., Petty E. M., Kalikin L. M., Church S. W., Mcllroy S., Harkin D. P., Keilty G. W., Cranston A. N., Weissenbach J., Hickey I., Johnston P. G. (2000) Isolation and mapping of a human septin gene to a region on chromosome 17q, commonly deleted in sporadic epithelial ovarian tumors. Cancer Res. 60: 4729-4734.  
     [0683] 4. Kinoshita A., Noda M., Kinoshita M. (2000) Differential localization of septins in the mouse brain. J. Comp. Neurol. 428: 223-239.  
     [0684] 5. Kinoshita A., Kinoshita M., Akiyama H., Tomimoto H., Akiguchi I., Kumar S., Noda M., Kimura J. (1998) Identification of septins in neurofibrillary tangles in Alzheimer&#39;s disease. Am. J. Pathol. 153: 1551-1560.  
     [0685] 6. Beites C. L., Xie H., Bowser R., Trimble W. S. (1999) The septin CDCrel-1 binds syntaxin and inhibits exocytosis. Nat. Neurosci. 2: 434439.  
     [0686] Panel 4.1D Summary: Ag4243 Highest expression of this gene is in the thymus (CT=28.3). In addition, moderate levels of expression are seen in many hematopoietic cell types, including activated and resting Th1, Th2, and Tr1 cells, LAK cells and B cells. Therefore, the putative protein encoded by this gene could potentially be used diagnostically to identify B or T cells. In addition, the gene product could also potentially be used therapeutically in the treatment of asthma, emphysema, IBD, lupus or arthritis and in other diseases in which T cells and B cells are involved.  
     [0687] Panel CNS — 1.1 Summary: Ag4243 This panel confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.  
     [0688] General oncology screening panel_v — 2.4 Summary: Ag4243 Highest expression of this gene is in the kidney cancer sample (CT=28.7). In addition, moderate to high expression of this gene is seen in number of cancer samples including melanoma, colon, lung, bladder, kidney and prostate cancers. Interestingly, expression of this gene is higher in some of the colon and lung cancers as compared to matching control samples. Therefore, expression of this gene may used as a diagnostic marker for detection of melanoma, lung, colon, prostate and kidney cancers. Furthermore, therapeutic modulation of this gene product may be useful in the treatment of these cancers.  
     J. CG102899-01: RIM2-4C  
     [0689] Expression of gene CG102899-01 was assessed using the primer-probe set Ag4247, described in Table JA. Results of the RTQ-PCR runs are shown in Tables JB, JC, JD, JE and JF.  
               TABLE JA                          Probe Name Ag4247                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-attagatgatgagccacattgg-3′   22   2586   116               Probe   TET-5′-acgcatgatgtctcttcattgccact-3′-TAMRA   26   2620   117               Reverse   5′-tgtcttcgtggcatatatgga-3′   21   2658   118                  
 
     [0690]               TABLE JB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4247, Run       Ag4247, Run       Tissue Name   224077628   Tissue Name   224077628                                     AD 1 Hippo   6.0   Control (Path) 3 Temporal   5.0               Ctx       AD 2 Hippo   13.7   Control (Path) 4 Temporal   37.9               Ctx       AD 3 Hippo   4.4   AD 1 Occipital Ctx   17.7       AD 4 Hippo   4.0   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   82.9   AD 3 Occipital Ctx   3.6       AD 6 Hippo   22.1   AD 4 Occipital Ctx   19.9       Control 2 Hippo   19.8   AD 5 Occipital Ctx   38.2       Control 4 Hippo   3.9   AD 6 Occipital Ctx   47.0       Control (Path) 3 Hippo   4.5   Control 1 Occipital Ctx   2.5       AD 1 Temporal Ctx   9.5   Control 2 Occipital Ctx   75.3       AD 2 Temporal Ctx   25.3   Control 3 Occipital Ctx   18.6       AD 3 Temporal Ctx   5.1   Control 4 Occipital Ctx   3.7       AD 4 Temporal Ctx   26.1   Control (Path) 1 Occipital   100.0               Ctx       AD 5 Inf Temporal Ctx   88.9   Control (Path) 2 Occipital   13.3               Ctx       AD 5 SupTemporal Ctx   10.6   Control (Path) 3 Occipital   1.4               Ctx       AD 6 Inf Temporal Ctx   42.3   Control (Path) 4 Occipital   14.2               Ctx       AD 6 Sup Temporal Ctx   44.4   Control 1 Parietal Ctx   7.4       Control 1 Temporal Ctx   6.3   Control 2 Parietal Ctx   32.8       Control 2 Temporal Ctx   47.0   Control 3 Parietal Ctx   20.3       Control 3 Temporal Ctx   18.7   Control (Path) 1 Parietal   97.9               Ctx       Control 4 Temporal Ctx   10.6   Control (Path) 2 Parietal   28.1               Ctx       Control (Path) 1 Temporal   67.4   Control (Path) 3 Parietal   3.9       Ctx       Ctx       Control (Path) 2 Temporal   50.3   Control (Path) 4 Parietal   49.3       Ctx       Ctx                    
     [0691]               TABLE JC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4247, Run       Ag4247, Run       Tissue Name   222019642   Tissue Name   222019642                                     Adipose   0.1   Renal ca. TK-10   24.7       Melanoma* Hs688(A).T   0.6   Bladder   1.3       Melanoma* Hs688(B).T   0.7   Gastric ca. (liver met.)   0.4               NCI-N87       Melanoma* M14   0.5   Gastric ca. KATO III   0.0       Melanoma* LOXIMVI   2.2   Colon ca. SW-948   0.0       Melanoma* SK-MEL-5   8.4   Colon ca. SW480   23.7       Squamous cell carcinoma   0.8   Colon ca.* (SW480 met)   0.7       SCC-4       SW620       Testis Pool   4.9   Colon ca. HT29   0.0       Prostate ca.* (bone met)   0.0   Colon ca. HCT-116   0.5       PC-3       Prostate Pool   4.9   Colon ca. CaCo-2   0.1       Placenta   0.0   Colon cancer tissue   0.0       Uterus Pool   0.4   Colon ca. SW1116   0.0       Ovarian ca. OVCAR-3   6.5   Colon ca. Colo-205   0.0       Ovarian ca. SK-OV-3   2.0   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   0.0   Colon Pool   1.1       Ovarian ca. OVCAR-5   0.4   Small Intestine Pool   0.2       Ovarian ca. IGROV-1   0.3   Stomach Pool   0.6       Ovarian ca. OVCAR-8   4.3   Bone Marrow Pool   0.1       Ovary   0.2   Fetal Heart   0.3       Breast ca. MCF-7   0.4   Heart Pool   1.1       Breast ca. MDA-MB-231   0.0   Lymph Node Pool   0.7       Breast ca. BT 549   6.0   Fetal Skeletal Muscle   0.0       Breast ca. T47D   0.4   Skeletal Muscle Pool   0.0       Breast ca. MDA-N   0.0   Spleen Pool   2.3       Breast Pool   1.4   Thymus Pool   0.8       Trachea   0.4   CNS cancer (glio/astro)   3.0               U87-MG       Lung   1.2   CNS cancer (glio/astro) U-   0.1               118-MG       Fetal Lung   0.7   CNS cancer (neuro; met)   4.5               SK-N-AS       Lung ca. NCI-N417   8.4   CNS cancer (astro) SF-   2.4               539       Lung ca. LX-1   4.5   CNS cancer (astro) SNB-   0.1               75       Lung ca. NCI-H146   35.6   CNS cancer (glio) SNB-19   0.0       Lung ca. SHP-77   100.0   CNS cancer (glio) SF-295   0.4       Lung ca. A549   0.1   Brain (Amygdala) Pool   48.0       Lung ca. NCI-H526   18.8   Brain (cerebellum)   43.2       Lung ca. NCI-H23   85.9   Brain (fetal)   42.3       Lung ca. NCI-H460   0.2   Brain (Hippocampus) Pool   45.1       Lung ca. HOP-62   0.8   Cerebral Cortex Pool   82.4       Lung ca. NCI-H522   22.1   Brain (Substantia nigra)   47.6               Pool       Liver   0.0   Brain (Thalamus) Pool   75.3       Fetal Liver   0.2   Brain (whole)   46.7       Liver ca. HepG2   0.0   Spinal Cord Pool   10.7       Kidney Pool   4.9   Adrenal Gland   7.2       Fetal Kidney   0.7   Pituitary gland Pool   21.8       Renal ca. 786-0   0.0   Salivary Gland   0.0       Renal ca. A498   0.0   Thyroid (female)   1.2       Renal ca. ACHN   12.5   Pancreatic ca. CAPAN2   0.1       Renal ca. UO-31   0.3   Pancreas Pool   1.4                    
     [0692]               TABLE JD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4247, Run       Ag4247, Run       Tissue Name   175165711   Tissue Name   175165711                                     Secondary Th1 act   1.0   HUVEC IL-1beta   3.3       Secondary Th2 act   17.2   HUVEC IFN gamma   27.0       Secondary Tr1 act   14.7   HUVEC TNF alpha + IFN   8.9               gamma       Secondary Th1 rest   2.1   HUVEC TNF alpha + IL4   3.7       Secondary Th2 rest   4.6   HUVEC IL-11   11.4       Secondary Tr1 rest   2.9   Lung Microvascular EC   0.0               none       Primary Th1 act   0.0   Lung Microvascular EC   0.0               TNF alpha + IL-1beta       Primary Th2 act   1.6   Microvascular Dermal EC   0.0               none       Primary Tr1 act   3.2   Microsvasular Dermal EC   0.0               TNF alpha + IL-1beta       Primary Th1 rest   0.5   Bronchial epithelium   20.0               TNF alpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium   2.2               none       Primary Tr1 rest   0.5   Small airway epithelium   4.8               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   1.2   Coronery artery SMC rest   0.0       act       CD45RO CD4 lymphocyte   0.4   Coronery artery SMC   1.6       act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   5.0       Secondary CD8 lymphocyte   0.6   Astrocytes TNF alpha +   8.5       rest       IL-1beta       Secondary CD8 lymphocyte   0.6   KU-812 (Basophil) rest   0.9       act       CD4 lymphocyte none   0.5   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   0.8   CCD1106 (Keratinocytes)   55.9       CH11       none       LAK cells rest   0.0   CCD1106 (Keratinocytes)   95.9               TNF alpha + IL-1beta       LAK cells IL-2   0.5   Liver cirrhosis   0.2       LAK cells IL-2 + IL-12   1.0   NCI-H292 none   21.2       LAK cells IL-2 + IFN gamma   0.7   NCI-H292 IL-4   25.3       LAK cells IL-2 + IL-18   0.5   NCI-H292 IL-9   28.7       LAK cells PMA/ionomycin   0.5   NCI-H292 IL-13   27.7       NK Cells IL-2 rest   0.0   NCI-H292 IFN gamma   28.7       Two Way MLR 3 day   0.0   HPAEC none   6.0       Two Way MLR 5 day   1.7   HPAEC TNF alpha +   14.9               IL-1beta       Two Way MLR 7 day   2.0   Lung fibroblast none   1.5       PBMC rest   0.0   Lung fibroblast   0.6               TNF alpha + IL-1beta       PBMC PWM   0.0   Lung fibroblast IL-4   0.6       PBMC PHA-L   1.5   Lung fibroblast IL-9   2.1       Ramos (B cell) none   3.8   Lung fibroblast IL-13   0.0       Ramos (B cell) ionomycin   1.8   Lung fibroblast IFN   3.4               gamma       B lymphocytes PWM   0.0   Dermal fibroblast   5.8               CCD1070 rest       B lymphocytes CD40L and   0.5   Dermal fibroblast   2.7       IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast   0.6               CCD1070 IL-1beta       EOL-1 dbcAMP   0.0   Dermal fibroblast IFN   6.8       PMA/ionomycin       gamma       Dendritic cells none   0.5   Dermal fibroblast IL-4   4.8       Dendritic cells LPS   2.5   Dermal Fibroblasts rest   3.6       Dendritic cells anti-CD40   0.6   Neutrophils TNFa + LPS   2.3       Monocytes rest   0.0   Neutrophils rest   0.2       Monocytes LPS   0.0   Colon   4.4       Macrophages rest   0.5   Lung   0.7       Macrophages LPS   0.0   Thymus   18.2       HUVEC none   0.0   Kidney   100.0       HUVEC starved   0.0                    
     [0693]               TABLE JE                          Panel CNS_1                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4247, Run       Ag4247,       Tissue Name   181012676   Tissue Name   Run 181012676                                     BA4 Control   34.2   BA17 PSP   29.3       BA4 Control2   60.7   BA17 PSP2   15.8       BA4 Alzheimer&#39;s2   5.6   Sub Nigra Control   20.4       BA4 Parkinson&#39;s   65.5   Sub Nigra Control2   16.2       BA4 Parkinson&#39;s2   97.3   Sub Nigra Alzheimer&#39;s2   4.3       BA4 Huntington&#39;s   48.0   Sub Nigra Parkinson&#39;s2   34.6       BA4 Huntington&#39;s2   13.5   Sub Nigra Huntington&#39;s   28.9       BA4 PSP   9.5   Sub Nigra Huntington&#39;s2   24.5       BA4 PSP2   24.1   Sub Nigra PSP2   3.3       BA4 Depression   14.4   Sub Nigra Depression   2.1       BA4 Depression2   9.9   Sub Nigra Depression2   1.5       BA7 Control   53.2   Glob Palladus Control   9.7       BA7 Control2   55.1   Glob Palladus Control2   10.3       BA7 Alzheimer&#39;s2   9.1   Glob Palladus Alzheimer&#39;s   4.3       BA7 Parkinson&#39;s   30.8   Glob Palladus   3.5               Alzheimer&#39;s2       BA7 Parkinson&#39;s2   58.6   Glob Palladus Parkinson&#39;s   97.9       BA7 Huntington&#39;s   68.8   Glob Palladus Parkinson&#39;s2   19.1       BA7 Huntington&#39;s2   75.3   Glob Palladus PSP   5.1       BA7 PSP   48.0   Glob Palladus PSP2   3.5       BA7 PSP2   35.6   Glob Palladus Depression   2.4       BA7 Depression   12.3   Temp Pole Control   21.5       BA9 Control   28.1   Temp Pole Control2   80.1       BA9 Control2   100.0   Temp Pole Alzheimer&#39;s   6.0       BA9 Alzheimer&#39;s   4.1   Temp Pole Alzheimer&#39;s2   3.6       BA9 Alzheimer&#39;s2   15.1   Temp Pole Parkinson&#39;s   45.7       BA9 Parkinson&#39;s   51.1   Temp Pole Parkinson&#39;s2   37.4       BA9 Parkinson&#39;s2   67.4   Temp Pole Huntington&#39;s   42.6       BA9 Huntington&#39;s   59.5   Temp Pole PSP   5.1       BA9 Huntington&#39;s2   27.0   Temp Pole PSP2   2.5       BA9 PSP   13.3   Temp Pole Depression2   5.2       BA9 PSP2   4.1   Cing Gyr Control   58.2       BA9 Depression   8.4   Cing Gyr Control2   31.9       BA9 Depression2   14.0   Cing Gyr Alzheimer&#39;s   15.9       BA17 Control   71.2   Cing Gyr Alzheimer&#39;s2   9.9       BA17 Control2   61.1   Cing Gyr Parkinson&#39;s   33.2       BA17 Alzheimer&#39;s2   5.1   Cing Gyr Parkinson&#39;s2   35.6       BA17 Parkinson&#39;s   45.4   Cing Gyr Huntington&#39;s   63.7       BA17 Parkinson&#39;s2   59.5   Cing Gyr Huntington&#39;s2   21.3       BA17 Huntington&#39;s   49.7   Cing Gyr PSP   10.4       BA17 Huntington&#39;s2   20.9   Cing Gyr PSP2   4.5       BA17 Depression   7.6   Cing Gyr Depression   7.6       BA17 Depression2   20.0   Cing Gyr Depression2   11.0                    
     [0694]               TABLE JF                          general oncology screening panel_v_2.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4247, Run       Ag4247, Run       Tissue Name   268664321   Tissue Name   268664321                                     Colon cancer 1   2.4   Bladder cancer NAT 2   0.0       Colon NAT 1   0.0   Bladder cancer NAT 3   15.9       Colon cancer 2   0.0   Bladder cancer NAT 4   1.3       Colon cancer NAT 2   2.9   Adenocarcinoma of the   30.8               prostate 1       Colon cancer 3   0.0   Adenocarcinoma of the   21.3               prostate 2       Colon cancer NAT 3   4.1   Adenocarcinoma of the   100.0               prostate 3       Colon malignant cancer 4   1.1   Adenocarcinoma of the   8.3               prostate 4       Colon normal adjacent   2.4   Prostate cancer NAT 5   4.5       tissue 4       Lung cancer 1   2.5   Adenocarcinoma of the   21.3               prostate 6       Lung NAT 1   0.0   Adenocarcinoma of the   35.1               prostate 7       Lung cancer 2   70.7   Adenocarcinoma of the   6.8               prostate 8       Lung NAT 2   0.0   Adenocarcinoma of the   54.0               prostate 9       Squamous cell carcinoma 3   56.3   Prostate cancer NAT 10   9.8       Lung NAT 3   0.0   Kidney cancer 1   0.0       metastatic melanoma 1   57.8   KidneyNAT 1   7.0       Melanoma 2   1.5   Kidney cancer 2   1.1       Melanoma 3   0.5   Kidney NAT 2   10.0       metastatic melanoma 4   32.8   Kidney cancer 3   0.0       metastatic melanoma 5   15.5   Kidney NAT 3   4.6       Bladder cancer 1   0.0   Kidney cancer 4   63.7       Bladder cancer NAT 1   0.0   Kidney NAT 4   4.5       Bladder cancer 2   45.1                    
     [0695] CNS_neurodegeneration_v1.0 Summary: Ag4247 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.  
     [0696] General_screening_panel_v1.4 Summary: Ag4247 Highest expression of this gene is seen in a lung cancer cell line (CT=26.1). In addition, significant levels of expression are seen in a cluster of lung cancer cell lines. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of lung cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of lung cancer.  
     [0697] In addition, this gene is expressed at high levels in all regions of the CNS examined. This gene is homologous to a RIM protein, a putative regulator of vesicle exocytosis during short-term plasticity. Thus, modulation of this gene product may be useful in the treatment of neurological disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0698] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adrenal gland, pancreas, thyroid, and adult and fetal heart. This expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0699] Panel 4.1D Summary: Ag4247 Highest expression of this gene is seen in the kidney (CT=30.6). Moderate levels of expression are seen in both treated and untreated keratinocytes, with low but significant levels of expression in thymus, dermal fibroblasts, HPAECs, HUVECs, astrocytes, activated bronchial and small airway epithelium, and the NCI-H292 cell line. Thus, modulation of the expression or activity of the protein encoded by this may be useful in the treatment of psoriasis, wound healing and other inflammatory conditions that involve these cells.  
     [0700] Panel CNS — 1 Summary: Ag4247 This panel confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.  
     [0701] General oncology screening panel_v — 2.4 Summary: Ag4247 Highest expression of this gene is seen in prostate cancer (CT=31.8). In addition, expression is seen in lung, kidney and melanoma cancers. The expression of this gene appears to be overexpressed in lung and kidney cancers when compared to expression in normal adjacent tissue. This prominent expression in cancer is in agreement with expression seen in Panel 1.4. Thus, modulation of the expression or function of this gene may be useful in the treatment of these cancers.  
     K. CG105444-01: Meningioma-Expressed Antigen 6/11 (MEA6) (MEA11)  
     [0702] Expression of gene CG105444-01 was assessed using the primer-probe set Ag4287, described in Table KA. Results of the RTQ-PCR runs are shown in Tables KB, KC and KD.  
               TABLE KA                          Probe Name Ag4287                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-attcatctctccctgctgaaa-3′   21   2123   119               Probe   TET-5′-ctggccttattcctccacctcttgct-3′-TAMRA   26   2159   120               Reverse   5′-tgtatccactggaaacaatgg-3′   21   2197   121                  
 
     [0703]               TABLE KB                          CNS_neurodegeneration_v1.0                                     Rel.   Rel.               Exp. (%)   Exp. (%)               Ag4287,   Ag4287,               Run   Run           Tissue Name   224075697   268773955                                             AD 1 Hippo   7.6   1.0           AD 2 Hippo   17.0   9.9           AD 3 Hippo   4.7   3.6           AD 4 Hippo   13.7   22.7           AD 5 hippo   100.0   65.1           AD 6 Hippo   43.2   77.9           Control 2 Hippo   33.7   4.0           Control 4 Hippo   23.0   39.0           Control (Path) 3   15.1   31.4           Hippo           AD 1 Temporal   7.6   3.3           Ctx           AD 2 Temporal   9.7   6.5           Ctx           AD 3 Temporal   2.5   14.4           Ctx           AD 4 Temporal   11.0   7.4           Ctx           AD 5 Inf   39.8   37.4           Temporal Ctx           AD 5   11.3   18.2           SupTemporal Ctx           AD 6 Inf   30.6   47.0           Temporal Ctx           AD 6 Sup   55.5   71.7           Temporal Ctx           Control 1   3.5   1.8           Temporal Ctx           Control 2   13.5   0.0           Temporal Ctx           Control 3   15.5   31.9           Temporal Ctx           Control 4   9.0   27.7           Temporal Ctx           Control (Path) 1   31.2   35.8           Temporal Ctx           Control (Path) 2   36.6   37.4           Temporal Ctx           Control (Path) 3   16.8   27.5           Temporal Ctx           Control (Path) 4   42.3   45.1           Temporal Ctx           AD 1 Occipital   44.4   28.7           Ctx           AD 2 Occipital   0.0   0.0           Ctx (Missing)           AD 3 Occipital   5.1   14.2           Ctx           AD 4 Occipital   10.7   11.6           Ctx           AD 5 Occipital   42.0   7.0           Ctx           AD 6 Occipital   23.5   7.7           Ctx           Control 1   6.6   22.4           Occipital Ctx           Control 2   24.3   2.7           Occipital Ctx           Control 3   25.3   100.0           Occipital Ctx           Control 4   10.3   9.2           Occipital Ctx           Control (Path) 1   66.9   22.4           Occipital Ctx           Control (Path) 2   10.3   3.7           Occipital Ctx           Control (Path) 3   4.0   13.6           Occipital Ctx           Control (Path) 4   32.5   54.3           Occipital Ctx           Control 1   13.0   9.9           Parietal Ctx           Control 2   27.4   37.6           Parietal Ctx           Control 3   22.1   17.3           Parietal Ctx           Control (Path) 1   33.2   37.1           Parietal Ctx           Control (Path) 2   17.4   23.7           Parietal Ctx           Control (Path) 3   3.8   26.6           Parietal Ctx           Control (Path) 4   46.7   55.1           Parietal Ctx                        
     [0704]               TABLE KC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4287, Run       Ag4287, Run       Tissue Name   222182747   Tissue Name   222182747                                     Adipose   9.8   Renal ca. TK-10   65.5       Melanoma* Hs688(A).T   9.1   Bladder   28.7       Melanoma* Hs688(B).T   9.5   Gastric ca. (liver met.) NCI-   12.4               N87       Melanoma* M14   5.0   Gastric ca. KATO III   46.7       Melanoma* LOXIMVI   0.2   Colon ca. SW-948   5.3       Melanoma* SK-MEL-5   0.2   Colon ca. SW480   100.0       Squamous cell carcinoma   11.7   Colon ca.* (SW480 met)   57.0       SCC-4       SW620       Testis Pool   18.7   Colon ca. HT29   25.0       Prostate ca.* (bone met)   20.0   Colon ca. HCT-116   19.2       PC-3       Prostate Pool   8.3   Colon ca. CaCo-2   8.5       Placenta   8.3   Colon cancer tissue   16.3       Uterus Pool   1.3   Colon ca. SW1116   10.1       Ovarian ca. OVCAR-3   21.2   Colon ca. Colo-205   5.9       Ovarian ca. SK-OV-3   13.4   Colon ca. SW-48   4.2       Ovarian ca. OVCAR-4   34.6   Colon Pool   22.8       Ovarian ca. OVCAR-5   47.6   Small Intestine Pool   10.6       Ovarian ca. IGROV-1   3.7   Stomach Pool   11.7       Ovarian ca. OVCAR-8   11.1   Bone Marrow Pool   7.3       Ovary   2.8   Fetal Heart   1.5       Breast ca. MCF-7   10.2   Heart Pool   2.5       Breast ca. MDA-MB-231   21.8   Lymph Node Pool   12.5       Breast ca. BT 549   0.2   Fetal Skeletal Muscle   3.1       Breast ca. T47D   57.4   Skeletal Muscle Pool   0.3       Breast ca. MDA-N   4.8   Spleen Pool   4.2       Breast Pool   9.8   Thymus Pool   13.8       Trachea   8.5   CNS cancer (glio/astro) U87-   0.2               MG       Lung   2.8   CNS cancer (glio/astro) U-   1.2               118-MG       Fetal Lung   55.9   CNS cancer (neuro; met) SK-   0.2               N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro) SF-539   0.1       Lung ca. LX-1   82.9   CNS cancer (astro) SNB-75   3.9       Lung ca. NCI-H146   0.3   CNS cancer (glio) SNB-19   3.0       Lung ca. SHP-77   0.3   CNS cancer (glio) SF-295   6.6       Lung ca. A549   0.5   Brain (Amygdala) Pool   0.3       Lung ca. NCI-H526   1.3   Brain (cerebellum)   0.5       Lung ca. NCI-H23   4.4   Brain (fetal)   1.4       Lung ca. NCI-H460   2.6   Brain (Hippocampus) Pool   0.6       Lung ca. HOP-62   2.1   Cerebral Cortex Pool   0.6       Lung ca. NCI-H522   0.1   Brain (Substantia nigra) Pool   1.3       Liver   0.2   Brain (Thalamus) Pool   1.2       Fetal Liver   1.8   Brain (whole)   1.3       Liver ca. HepG2   6.0   Spinal Cord Pool   1.2       Kidney Pool   8.0   Adrenal Gland   3.6       Fetal Kidney   38.7   Pituitary gland Pool   3.3       Renal ca. 786-0   25.5   Salivary Gland   3.1       Renal ca. A498   43.5   Thyroid (female)   12.5       Renal ca. ACHN   4.5   Pancreatic ca. CAPAN2   30.1       Renal ca. UO-31   14.0   Pancreas Pool   24.8                    
     [0705]               TABLE KD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4287, Run       Ag4287, Run       Tissue Name   182392142   Tissue Name   182392142                                     Secondary Th1 act   5.1   HUVEC IL-1beta   0.8       Secondary Th2 act   14.8   HUVEC IFN gamma   20.6       Secondary Tr1 act   6.2   HUVEC TNF alpha + IFN   9.1               gamma       Secondary Th1 rest   8.5   HUVEC TNF alpha + IL4   3.4       Secondary Th2 rest   17.8   HUVEC IL-11   0.9       Secondary Tr1 rest   16.2   Lung Microvascular EC none   2.9       Primary Th1 act   9.0   Lung Microvascular EC   0.8               TNF alpha + IL-1beta       Primary Th2 act   14.3   Microvascular Dermal EC   0.1               none       Primary Tr1 act   8.4   Microsvasular Dermal EC   0.0               TNF alpha + IL-1beta       Primary Th1 rest   4.0   Bronchial epithelium   28.9               TNF alpha + IL1beta       Primary Th2 rest   2.6   Small airway epithelium none   8.1       Primary Tr1 rest   9.3   Small airway epithelium   37.4               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   8.7   Coronery artery SMC rest   5.4       act       CD45RO CD4 lymphocyte   20.0   Coronery artery SMC   5.8       act       TNF alpha + IL-1beta       CD8 lymphocyte act   4.9   Astrocytes rest   0.3       Secondary CD8 lymphocyte   10.4   Astrocytes TNF alpha + IL-   0.6       rest       1beta       Secondary CD8 lymphocyte   7.6   KU-812 (Basophil) rest   20.9       act       CD4 lymphocyte none   3.8   KU-812 (Basophil)   79.6               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   23.5   CCD1106 (Keratinocytes)   45.1       CD95 CH11       none       LAK cells rest   5.2   CCD1106 (Keratinocytes)   52.5               TNF alpha + IL-1beta       LAK cells IL-2   2.0   Liver cirrhosis   14.8       LAK cells IL-2 + IL-12   4.4   NCI-H292 none   23.0       LAK cells IL-2 + IFN   8.0   NCI-H292 IL-4   25.0       gamma       LAK cells IL-2 + IL-18   5.2   NCI-H292 IL-9   31.6       LAK cells PMA/ionomycin   6.9   NCI-H292 IL-13   36.6       NK Cells IL-2 rest   6.0   NCI-H292 IFN gamma   34.4       Two Way MLR 3 day   12.7   HPAEC none   1.3       Two Way MLR 5 day   6.7   HPAEC TNF alpha +   1.6               IL-1beta       Two Way MLR 7 day   11.5   Lung fibroblast none   10.7       PBMC rest   2.0   Lung fibroblast TNF alpha +   2.7               IL-1beta       PBMC PWM   5.2   Lung fibroblast IL-4   3.5       PBMC PHA-L   15.1   Lung fibroblast IL-9   8.0       Ramos (B cell) none   0.0   Lung fibroblast IL-13   4.8       Ramos (B cell) ionomycin   0.1   Lung flbroblast IFN gamma   8.8       B lymphocytes PWM   5.3   Dermal fibroblast CCD1070   3.4               rest       B lymphocytes CD40L and   10.4   Dermal fibroblast CCD1070   23.5       IL-4       TNF alpha       EOL-1 dbcAMP   0.1   Dermal fibroblast CCD1070   2.3               IL-1beta       EOL-1 dbcAMP   0.0   Dermal fibroblast IFN gamma   7.1       PMA/ionomycin       Dendritic cells none   0.0   Dermal fibroblast IL-4   7.4       Dendritic cells LPS   0.1   Dermal Fibroblasts rest   5.1       Dendritic cells anti-CD40   0.0   Neutrophils TNFa + LPS   3.2       Monocytes rest   0.1   Neutrophils rest   0.1       Monocytes LPS   0.4   Colon   15.3       Macrophages rest   0.6   Lung   19.2       Macrophages LPS   1.0   Thymus   38.7       HUVEC none   0.2   Kidney   100.0       HUVEC starved   0.8                    
     [0706] CNS_neurodegeneration_v1.0 Summary: Ag4287 Two experiments with same probe and primer sets are in good agreement. This panel confirms the expression of the CG105444-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer&#39;s diseased postmortem brains and those of non-demented controls in this experiment. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.  
     [0707] General_screening_panel_v1.4 Summary: Ag4287 Highest expression of the CG105444-01 gene is detected in colon cancer SW480 cell line (CT=26.3). Significant expression is also seen in number of cancer cell lines derived from colon, renal, lung, liver, breast, ovarian, and brain cancers. Thus, expression of this gene may be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, renal, lung, liver, breast, ovarian, and brain cancers.  
     [0708] The CG 1 105444-01 gene encodes a homolog of meningioma-expressed antigen 6/11 (MEA6). MGEA6 is overexpressed in meningioma and glioma tumor cells. Furthermore, the immune response to MGEA6/11 is frequent in both meningioma and glioma patients (Comtesse et al., 2002, Oncogene 21(2):239-47, PMID: 11803467). Thus, based on the homology, MEA6 like protein encoded by the CG105463-01 gene may play a role in pathology of meningioma and glioma and therapeutic modulation of this gene may be beneficial in the treatment of these tumors.  
     [0709] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, skeletal muscle, fetal heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.  
     [0710] Interestingly, this gene is expressed at much higher levels in fetal (CTs=27-32) when compared to adult liver, lung and skeletal muscle (CTs=3 1.5-35). This observation suggests that expression of this gene can be used to distinguish fetal liver, lung and skeletal muscle from corresponding adult tissues. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance growth or development of liver, lung and skeletal muscle in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of MEA6 like protein encoded by this gene could be useful in treatment of liver, lung and skeletal muscle related diseases.  
     [0711] In addition, this gene is expressed at moderate to low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer&#39;s disease, Parkinson&#39;s disease, epilepsy, multiple sclerosis, schizophrenia and depression.  
     [0712] Panel 4.1D Summary: Ag4287 Highest expression of the CG105444-01 gene is detected in kidney (CT=29). This gene is expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     L. CG105482-01: Meningioma-Expressed Antigen 6/11 (MEA6) (MEA11)  
     [0713] Expression of gene CG105482-01 was assessed using the primer-probe set Ag4319, described in Table LA. Results of the RTQ-PCR runs are shown in Tables LB, LC and LD.  
               TABLE LA                          Probe Name Ag4319                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-gggtcaatgccttcagaaat-3′   20   2047   122               Probe   TET-5′-agacatgatgccaaagatgatcctgg-3′-TAMRA   26   2077   123               Reverse   5′-cagcagggagagatgaatca-3′   20   2118   124                  
 
     [0714]               TABLE LB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4319, Run       Ag4319, Run       Tissue Name   224074994   Tissue Name   224074994                                     AD 1 Hippo   7.6   Control (Path) 3 Temporal   38.2               Ctx       AD 2 Hippo   20.9   Control (Path) 4 Temporal   36.9               Ctx       AD 3 Hippo   11.3   AD 1 Occipital Ctx   61.6       AD 4 Hippo   6.7   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   41.8   AD 3 Occipital Ctx   18.2       AD 6 Hippo   12.9   AD 4 Occipital Ctx   5.2       Control 2 Hippo   7.9   AD 5 Occipital Ctx   0.0       Control 4 Hippo   11.6   AD 6 Occipital Ctx   0.0       Control (Path) 3 Hippo   10.4   Control 1 Occipital Ctx   4.6       AD 1 Temporal Ctx   26.8   Control 2 Occipital Ctx   13.0       AD 2 Temporal Ctx   5.3   Control 3 Occipital Ctx   100.0       AD 3 Temporal Ctx   14.4   Control 4 Occipital Ctx   12.9       AD 4 Temporal Ctx   35.1   Control (Path) 1 Occipital   22.5               Ctx       AD 5 Inf Temporal Ctx   26.8   Control (Path) 2 Occipital   25.0               Ctx       AD 5 Sup Temporal Ctx   26.1   Control (Path) 3 Occipital   0.0               Ctx       AD 6 Inf Temporal Ctx   0.0   Control (Path) 4 Occipital   36.3               Ctx       AD 6 Sup Temporal Ctx   8.5   Control 1 Parietal Ctx   18.7       Control 1 Temporal Ctx   15.9   Control 2 Parietal Ctx   80.7       Control 2 Temporal Ctx   0.0   Control 3 Parietal Ctx   13.3       Control 3 Temporal Ctx   13.5   Control (Path) 1 Parietal   25.3               Ctx       Control 4 Temporal Ctx   0.0   Control (Path) 2 Parietal   15.6               Ctx       Control (Path) 1 Temporal   44.4   Control (Path) 3 Parietal   25.0       Ctx       Ctx       Control (Path) 2 Temporal   56.3   Control (Path) 4 Parietal   14.7       Ctx       Ctx                    
     [0715]               TABLE LC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4319, Run       Ag4319, Run       Tissue Name   222523501   Tissue Name   222523501                                     Adipose   1.4   Renal ca. TK-10   0.0       Melanoma* Hs688(A).T   0.0   Bladder   8.8       Melanoma* Hs688(B).T   0.0   Gastric ca. (liver met.)   0.0               NCI-N87       Melanoma* M14   0.0   Gastric ca. KATO III   0.0       Melanoma* LOXIMVI   0.0   Colon ca. SW-948   0.0       Melanoma* SK-MEL-5   0.0   Colon ca. SW480   0.0       Squamous cell carcinoma   0.0   Colon ca.* (SW480 met)   0.0       SCC-4       SW620       Testis Pool   11.7   Colon ca. HT29   0.0       Prostate ca.* (bone met) PC-3   0.0   Colon ca. HCT-116   0.0       Prostate Pool   0.0   Colon ca. CaCo-2   0.0       Placenta   0.0   Colon cancer tissue   0.0       Uterus Pool   0.0   Colon ca. SW1116   0.0       Ovarian ca. OVCAR-3   15.8   Colon ca. Colo-205   0.0       Ovarian ca. SK-OV-3   0.0   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   0.0   Colon Pool   0.0       Ovarian ca. OVCAR-5   0.0   Small Intestine Pool   0.0       Ovarian ca. IGROV-1   10.0   Stomach Pool   0.0       Ovarian ca. OVCAR-8   0.0   Bone Marrow Pool   0.0       Ovary   0.0   Fetal Heart   0.0       Breast ca. MCF-7   0.0   Heart Pool   0.0       Breast ca. MDA-MB-231   0.0   Lymph Node Pool   0.0       Breast ca. BT 549   1.4   Fetal Skeletal Muscle   0.0       Breast ca. T47D   0.0   Skeletal Muscle Pool   0.0       Breast ca. MDA-N   3.7   Spleen Pool   0.0       Breast Pool   0.0   Thymus Pool   0.0       Trachea   0.0   CNS cancer (glio/astro)   0.0               U87-MG       Lung   0.0   CNS cancer (glio/astro) U-   0.0               118-MG       Fetal Lung   0.0   CNS cancer (neuro; met)   22.7               SK-N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro) SF-539   0.0       Lung ca. LX-1   0.0   CNS cancer (astro) SNB-   47.3               75       Lung ca. NCI-H146   0.0   CNS cancer (glio) SNB-19   14.4       Lung ca. SHP-77   0.0   CNS cancer (glio) SF-295   0.0       Lung ca. A549   0.0   Brain (Amygdala) Pool   4.8       Lung ca. NCI-H526   0.0   Brain (cerebellum)   0.0       Lung ca. NCI-H23   0.0   Brain (fetal)   100.0       Lung ca. NCI-H460   0.0   Brain (Hippocampus) Pool   15.3       Lung ca. HOP-62   0.0   Cerebral Cortex Pool   51.1       Lung ca. NCI-H522   0.0   Brain (Substantia nigra)   13.9               Pool       Liver   0.0   Brain (Thalamus) Pool   8.7       Fetal Liver   0.0   Brain (whole)   18.4       Liver ca. HepG2   0.0   Spinal Cord Pool   1.5       Kidney Pool   0.0   Adrenal Gland   0.0       Fetal Kidney   0.0   Pituitary gland Pool   0.0       Renal ca. 786-0   7.0   Salivary Gland   0.0       Renal ca. A498   10.4   Thyroid (female)   0.0       Renal ca. ACHN   0.0   Pancreatic ca. CAPAN2   0.0       Renal ca. UO-31   0.0   Pancreas Pool   0.0                    
     [0716]               TABLE LD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4319, Run       Ag4319, Run       Tissue Name   182392175   Tissue Name   182392175                                     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   0.0   Microsvasular Dermal EC   0.0               TNF alpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   0.0               TNF alpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium   0.0               none       Primary Tr1 rest   0.0   Small airway epithelium   0.0               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   0.0   Coronery artery SMC rest   0.0       act       CD45RO CD4 lymphocyte   0.0   Coronery artery SMC   0.0       act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   0.0       Secondary CD8 lymphocyte   0.0   Astrocytes TNF alpha + IL-   0.0       rest       1beta       Secondary CD8 lymphocyte   0.0   KU-812 (Basophil) rest   0.0       act       CD4 lymphocyte none   0.0   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   0.0   CCD1106 (Keratinocytes)   0.0       CH11       none       LAK cells rest   0.0   CCD1106 (Keratinocytes)   0.0               TNF alpha + IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   0.0       LAK cells IL-2 + IL-12   0.0   NCI-H292 none   0.0       LAK cells IL-2 + IFN gamma   0.0   NCI-H292 IL-4   0.0       LAK cells IL-2 + IL-18   0.0   NCI-H292 IL-9   0.0       LAK cells PMA/ionomycin   0.0   NCI-H292 IL-13   0.0       NK Cells IL-2 rest   0.0   NCI-H292 IFN gamma   0.0       Two Way MLR 3 day   0.0   HPAEC none   0.0       Two Way MLR 5 day   0.0   HPAEC TNF alpha +   0.0               IL-1beta       Two Way MLR 7 day   0.0   Lung fibroblast none   0.0       PBMC rest   0.0   Lung fibroblast   0.0               TNF alpha + IL-1beta       PBMC PWM   0.0   Lung fibroblast IL-4   0.0       PBMC PHA-L   0.0   Lung fibroblast IL-9   0.0       Ramos (B cell) none   0.0   Lung fibroblast IL-13   0.0       Ramos (B cell) ionomycin   0.0   Lung fibroblast IFN   0.0               gamma       B lymphocytes PWM   0.0   Dermal fibroblast   0.0               CCD1070 rest       B lymphocytes CD40L and   0.0   Dermal fibroblast   0.0       IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast   0.0               CCD1070 IL-1beta       EOL-1 dbcAMP   0.0   Dermal fibroblast IFN   0.0       PMA/ionomycin       gamma       Dendritic cells none   0.0   Dermal fibroblast IL-4   0.0       Dendritic cells LPS   0.0   Dermal Fibroblasts rest   0.0       Dendritic cells anti-CD40   0.0   Neutrophils TNFa + LPS   0.0       Monocytes rest   0.0   Neutrophils rest   0.0       Monocytes LPS   0.0   Colon   0.0       Macrophages rest   0.0   Lung   0.0       Macrophages LPS   0.0   Thymus   0.0       HUVEC none   0.0   Kidney   100.0       HUVEC starved   0.0                    
     [0717] CNS_neurodegeneration_v1.0 Summary: Ag4319 This panel confirms the expression of the CG105482-01 gene at low levels in the brains of an independent group of individuals. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.  
     [0718] General_screening_panel_v1.4 Summary: Ag4319 Highest expression of the CG105482-01 gene is detected in fetal brain (CT=32.9). This gene is also expressed at low levels in cerebral cortex and a CNS cancer SNB-75 cell line. Therefore, expression of this gene may be used to distinguish brain samples from other samples used in this panel. Also, therapeutic modulation of this gene may be beneficial in the treatment of brain related diseases including brain cancer, and neurological disorders such as seizure and Huntington&#39;s disease.  
     [0719] The CG105482-01 gene encodes a homolog of meningioma-expressed antigen 6/11 (MEA6). MGEA6 is overexpressed in meningioma and glioma tumor cells. Furthermore, the immune response to MGEA6/11 is frequent in both meningioma and glioma patients (Comtesse et al., 2002, Oncogene 21(2):239-47, PMID: 11803467). Thus, based on the homology, MEA6 like protein encoded by the CG105482-01 gene may play a role in pathology of meningioma and glioma and therapeutic modulation of this gene may be beneficial in the treatment of these tumors.  
     [0720] Panel 4.1D Summary: Ag4319 Low levels of expression of the CG105482-01 gene is detected in kidney (CT=34.9). Therefore, expression of this gene may be used to distinguish kidney from other samples used in this panel. Furthermore, therapeutic modulation of this gene product may be useful in the treatment of autoimmune and inflammatory disease that affect kidney, including lupus and glomerulonephritis.  
     M. CG105617-01: Liprin alpha4  
     [0721] Expression of gene CG105617-01 was assessed using the primer-probe set Ag4294, described in Table MA.  
               TABLE MA                          Probe Name Ag4294                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tgccctactctgtttcttgtca-3′   22   691   125               Probe   TET-5′-atttctccctgccatggctggaag-3′-TAMRA   24   714   126               Reverse   5′-gggatagggacagtagctctgt-3′   22   748   127                  
 
     N. CG105638-01: Ankyrin-like Q9GKW8 Homolog  
     [0722] Expression of gene CG105638-01 was assessed using the primer-probe set Ag3745, described in Table NA. Results of the RTQ-PCR runs are shown in Tables NB, NC, ND and NE.  
               TABLE NA                          Probe Name Ag3745                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-cctggtggacatgatcataaaa-3′   22   717   128               Probe   TET-5′-ctacagatgggagaagaccaccccag-3′-TAMRA   26   750   129               Reverse   5′-cctgcttaaaggacaagctctt-3′   22   789   130                  
 
     [0723]               TABLE NB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag3745, Run       Ag3745, Run       Tissue Name   212143924   Tissue Name   212143924                                     AD 1 Hippo   33.7   Control (Path) 3 Temporal   9.7               Ctx       AD 2 Hippo   45.7   Control (Path) 4 Temporal   59.0               Ctx       AD 3 Hippo   4.8   AD 1 Occipital Ctx   15.6       AD 4 Hippo   21.8   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   48.0   AD 3 Occipital Ctx   4.0       AD 6 Hippo   77.9   AD 4 Occipital Ctx   35.4       Control 2 Hippo   35.6   AD 5 Occipital Ctx   19.6       Control 4 Hippo   26.2   AD 6 Occipital Ctx   48.3       Control (Path) 3 Hippo   7.2   Control 1 Occipital Ctx   3.3       AD 1 Temporal Ctx   18.9   Control 2 Occipital Ctx   43.5       AD 2 Temporal Ctx   40.6   Control 3 Occipital Ctx   16.4       AD 3 Temporal Ctx   6.5   Control 4 Occipital Ctx   14.5       AD 4 Temporal Ctx   40.1   Control (Path) 1 Occipital   64.6               Ctx       AD 5 Inf Temporal Ctx   81.8   Control (Path) 2 Occipital   7.6               Ctx       AD 5 SupTemporal Ctx   69.7   Control (Path) 3 Occipital   1.8               Ctx       AD 6 Inf Temporal Ctx   75.8   Control (Path) 4 Occipital   17.1               Ctx       AD 6 Sup Temporal Ctx   100.0   Control 1 Parietal Ctx   10.9       Control 1 Temporal Ctx   8.7   Control 2 Parietal Ctx   52.9       Control 2 Temporal Ctx   45.7   Control 3 Parietal Ctx   22.2       Control 3 Temporal Ctx   16.7   Control (Path) 1 Parietal   68.3               Ctx       Control 4 Temporal Ctx   16.7   Control (Path) 2 Parietal   33.7               Ctx       Control (Path) 1 Temporal   73.7   Control (Path) 3 Parietal   6.1       Ctx       Ctx       Control (Path) 2 Temporal   51.8   Control (Path) 4 Parietal   60.3       Ctx       Ctx                    
     [0724]               TABLE NC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag3745, Run       Ag3745, Run       Tissue Name   218297930   Tissue Name   218297930                                     Adipose   11.3   Renal ca. TK-10   0.6       Melanoma* Hs688(A).T   16.3   Bladder   18.4       Melanoma* Hs688(B).T   8.4   Gastric ca. (liver met.)   32.5               NCI-N87       Melanoma* M14   9.0   Gastric ca. KATO III   0.3       Melanoma* LOXIMVI   2.6   Colon ca. SW-948   0.3       Melanoma* SK-MEL-5   6.7   Colon ca. SW480   4.5       Squamous cell carcinoma   5.6   Colon ca.* (SW480 met)   5.4       SCC-4       SW620       Testis Pool   36.3   Colon ca. HT29   0.8       Prostate ca.* (bone met) PC-3   11.4   Colon ca. HCT-116   42.6       Prostate Pool   17.2   Colon ca. CaCo-2   0.5       Placenta   22.2   Colon cancer tissue   7.0       Uterus Pool   12.4   Colon ca. SW1116   0.6       Ovarian ca. OVCAR-3   4.5   Colon ca. Colo-205   0.4       Ovarian ca. SK-OV-3   9.3   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   7.1   Colon Pool   34.2       Ovarian ca. OVCAR-5   41.2   Small Intestine Pool   21.2       Ovarian ca. IGROV-1   1.5   Stomach Pool   15.9       Ovarian ca. OVCAR-8   9.9   Bone Marrow Pool   18.0       Ovary   32.3   Fetal Heart   3.6       Breast ca. MCF-7   0.6   Heart Pool   18.8       Breast ca. MDA-MB-231   4.3   Lymph Node Pool   31.6       Breast ca. BT 549   6.7   Fetal Skeletal Muscle   3.7       Breast ca. T47D   56.6   Skeletal Muscle Pool   1.5       Breast ca. MDA-N   0.5   Spleen Pool   100.0       Breast Pool   31.0   Thymus Pool   14.6       Trachea   18.9   CNS cancer (glio/astro)   20.0               U87-MG       Lung   16.8   CNS cancer (glio/astro)   14.9               U-118-MG       Fetal Lung   25.5   CNS cancer (neuro; met)   17.9               SK-N-AS       Lung ca. NCI-N417   1.6   CNS cancer (astro) SF-   17.8               539       Lung ca. LX-1   4.1   CNS cancer (astro) SNB-   67.8               75       Lung ca. NCI-H146   0.9   CNS cancer (glio) SNB-   2.2               19       Lung ca. SHP-77   0.9   CNS cancer (glio) SF-295   13.9       Lung ca. A549   10.9   Brain (Amygdala) Pool   26.4       Lung ca. NCI-H526   28.3   Brain (cerebellum)   55.5       Lung ca. NCI-H23   33.2   Brain (fetal)   49.3       Lung ca. NCI-H460   4.0   Brain (Hippocampus) Pool   42.9       Lung ca. HOP-62   11.8   Cerebral Cortex Pool   53.6       Lung ca. NCI-H522   28.5   Brain (Substantia nigra)   42.3               Pool       Liver   0.6   Brain (Thalamus) Pool   58.2       Fetal Liver   1.7   Brain (whole)   26.4       Liver ca. HepG2   0.2   Spinal Cord Pool   51.8       Kidney Pool   78.5   Adrenal Gland   74.2       Fetal Kidney   7.5   Pituitary gland Pool   1.4       Renal ca. 786-0   1.0   Salivary Gland   3.3       Renal ca. A498   3.1   Thyroid (female)   7.5       Renal ca. ACHN   1.0   Pancreatic ca. CAPAN2   12.3       Renal ca. UO-31   3.4   Pancreas Pool   25.9                    
     [0725]               TABLE ND                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag3745, Run       Ag3745, Run       Tissue Name   170068389   Tissue Name   170068389                                     Secondary Th1 act   12.2   HUVEC IL-1beta   0.0       Secondary Th2 act   36.6   HUVEC IFN gamma   12.9       Secondary Tr1 act   54.3   HUVEC TNF alpha + IFN   8.8               gamma       Secondary Th1 rest   1.2   HUVEC TNF alpha + IL4   8.7       Secondary Th2 rest   11.8   HUVEC IL-11   7.7       Secondary Tr1 rest   8.1   Lung Microvascular EC   17.6               none       Primary Th1 act   4.8   Lung Microvascular EC   28.1               TNF alpha + IL-1beta       Primary Th2 act   1.8   Microvascular Dermal EC   13.0               none       Primary Tr1 act   1.5   Microsvasular Dermal EC   22.1               TNF alpha + IL-1beta       Primary Th1 rest   34.6   Bronchial epithelium   28.3               TNF alpha + IL1beta       Primary Th2 rest   14.3   Small airway epithelium   6.9               none       Primary Tr1 rest   47.6   Small airway epithelium   8.5               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   17.3   Coronery artery SMC rest   9.5       act       CD45RO CD4 lymphocyte   45.1   Coronery artery SMC   11.7       act       TNF alpha + IL-1beta       CD8 lymphocyte act   8.9   Astrocytes rest   5.1       Secondary CD8 lymphocyte   46.7   Astrocytes TNF alpha +   1.8       rest       IL-1beta       Secondary CD8 lymphocyte   39.8   KU-812 (Basophil) rest   9.3       act       CD4 lymphocyte none   11.7   KU-812 (Basophil)   14.1               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   28.7   CCD1106 (Keratinocytes)   8.5       CH11       none       LAK cells rest   34.6   CCD1106 (Keratinocytes)   3.9               TNF alpha + IL-1beta       LAK cells IL-2   36.6   Liver cirrhosis   6.0       LAK cells IL-2 + IL-12   20.4   NCI-H292 none   2.4       LAK cells IL-2 + IFN gamma   47.0   NCI-H292 IL-4   0.0       LAK cells IL-2 + IL-18   27.5   NCI-H292 IL-9   0.0       LAK cells PMA/ionomycin   11.0   NCI-H292 IL-13   2.0       NK Cells IL-2 rest   94.0   NCI-H292 IFN gamma   0.0       Two Way MLR 3 day   23.7   HPAEC none   6.6       Two Way MLR 5 day   11.1   HPAEC TNF alpha +   8.0               IL-1beta       Two Way MLR 7 day   46.3   Lung fibroblast none   100.0       PBMC rest   12.6   Lung fibroblast   27.5               TNF alpha + IL-1beta       PBMC PWM   12.9   Lung fibroblast IL-4   44.8       PBMC PHA-L   5.7   Lung fibroblast IL-9   38.7       Ramos (B cell) none   9.7   Lung fibroblast IL-13   35.8       Ramos (B cell) ionomycin   23.3   Lung fibroblast IFN   69.3               gamma       B lymphocytes PWM   1.4   Dermal fibroblast   10.3               CCD1070 rest       B lymphocytes CD40L and   7.9   Dermal fibroblast   68.8       IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   1.6   Dermal fibroblast   5.7               CCD1070 IL-1beta       EOL-1 dbcAMP   20.7   Dermal fibroblast IFN   43.2       PMA/ionomycin       gamma       Dendritic cells none   28.1   Dermal fibroblast IL-4   80.7       Dendritic cells LPS   35.6   Dermal Fibroblasts rest   36.6       Dendritic cells anti-CD40   18.3   Neutrophils TNFa + LPS   11.0       Monocytes rest   22.7   Neutrophils rest   19.5       Monocytes LPS   27.5   Colon   6.1       Macrophages rest   42.0   Lung   13.9       Macrophages LPS   12.2   Thymus   50.7       HUVEC none   3.6   Kidney   10.5       HUVEC starved   6.8                    
     [0726]               TABLE NE                          general oncology screening panel_v_2.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag3745, Run       Ag3745, Run       Tissue Name   268389961   Tissue Name   268389961                                     Colon cancer 1   6.2   Bladder cancer NAT 2   0.8       Colon cancer NAT 1   5.2   Bladder cancer NAT 3   2.1       Colon cancer 2   3.6   Bladder cancer NAT 4   5.7       Colon cancer NAT 2   4.5   Adenocarcinoma of the   69.3               prostate 1       Colon cancer 3   7.6   Adenocarcinoma of the   4.5               prostate 2       Colon cancer NAT 3   14.0   Adenocarcinoma of the   14.6               prostate 3       Colon malignant cancer 4   6.0   Adenocarcinoma of the   7.2               prostate 4       Colon normal adjacent tissue 4   0.0   Prostate cancer NAT 5   3.5       Lung cancer 1   7.2   Adenocarcinoma of the   4.8               prostate 6       Lung NAT 1   4.5   Adenocarcinoma of the   8.8               prostate 7       Lung cancer 2   12.5   Adenocarcinoma of the   1.7               prostate 8       Lung NAT 2   3.1   Adenocarcinoma of the   33.2               prostate 9       Squamous cell carcinoma 3   6.1   Prostate cancer NAT 10   2.1       Lung NAT 3   0.4   Kidney cancer 1   7.2       metastatic melanoma 1   37.1   KidneyNAT 1   2.0       Melanoma 2   3.2   Kidney cancer 2   27.7       Melanoma 3   3.1   Kidney NAT 2   7.6       metastatic melanoma 4   62.9   Kidney cancer 3   3.7       metastatic melanoma 5   100.0   Kidney NAT 3   3.4       Bladder cancer 1   2.9   Kidney cancer 4   4.1       Bladder cancer NAT 1   0.0   Kidney NAT 4   4.0       Bladder cancer 2   10.7                    
     [0727] CNS_neurodegeneration_v1.0 Summary: Ag3745 This panel does not show differential expression of this gene in Alzheimer&#39;s disease. However, this expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.  
     [0728] General_screening_panel_v1.4 Summary: Ag3745 Highest expression of this gene is seen in the spleen (CT=29.6). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, and ovarian cancer cell lines. Modulation of this gene product may be useful in the treatment of cancer.  
     [0729] Among tissues with metabolic function, this gene is expressed at moderate to low levels in adipose, adrenal gland, pancreas, thyroid, fetal skeletal muscle and adult and fetal heart. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0730] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0731] Panel 4.ID Summary: Ag3745 Highest expression of this gene is seen in IL-4 treated fibroblasts (CT=31.2). In addition, prominent levels of expression are seen in treated and untreated lung and dermal fibroblasts, LAK cells, CD8 lymphocytes, chronically activated T cells, and primary resting T cells. Thus, this gene product may be involved in inflammatory conditions of the lung and skin, and T cell mediated autoimmune or inflammatory diseases, including asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis.  
     [0732] General oncology screening panel_V — 2.4 Summary: Ag3745 Highest expression of this gene is seen in melanoma (CT=30.3). In addition, significant expression is seen in prostate and kidney cancer. This gene is overexpressed in kidney cancer when compared to expression in normal adjacent tissue. Thus, modulation of the expression or function of this gene may be useful in the treatment of these cancers.  
     O. CG105671-01: Novel GTPase Acivator Protein  
     [0733] Expression of gene CG105671 -01 was assessed using the primer-probe set Ag4295, described in Table OA. Results of the RTQ-PCR runs are shown in Tables OB, OC and OD.  
               TABLE OA                          Probe Name Ag4295                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-aacaaagaaagtggaggtggat-3′   22   1600   131               Probe   TET-5′-cccacttacaaatgtcttcacgatgca-3′-TAMRA   27   1629   132               Reverse   5′-catgtggcaaagagagtcaga-3′   21   1662   133                  
 
     [0734]               TABLE OB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4295, Run       Ag4295, Run       Tissue Name   224073754   Tissue Name   224073754                                     AD 1 Hippo   4.5   Control (Path) 3 Temporal   2.0               Ctx       AD 2 Hippo   12.2   Control (Path) 4 Temporal   15.5               Ctx       AD 3 Hippo   2.1   AD 1 Occipital Ctx   8.5       AD 4 Hippo   3.1   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   100.0   AD 3 Occipital Ctx   1.1       AD 6 Hippo   18.2   AD 4 Occipital Ctx   8.4       Control 2 Hippo   15.4   AD 5 Occipital Ctx   34.4       Control 4 Hippo   1.3   AD 6 Occipital Ctx   11.2       Control (Path) 3 Hippo   3.1   Control 1 Occipital Ctx   1.1       AD 1 Temporal Ctx   2.1   Control 2 Occipital Ctx   48.6       AD 2 Temporal Ctx   13.1   Control 3 Occipital Ctx   6.7       AD 3 Temporal Ctx   2.1   Control 4 Occipital Ctx   1.1       AD 4 Temporal Ctx   6.0   Control (Path) 1 Occipital   51.8               Ctx       AD 5 Inf Temporal Ctx   45.7   Control (Path) 2 Occipital   6.3               Ctx       AD 5 Sup Temporal Ctx   17.2   Control (Path) 3 Occipital   1.1               Ctx       AD 6 Inf Temporal Ctx   19.1   Control (Path) 4 Occipital   7.6               Ctx       AD 6 Sup Temporal Ctx   18.0   Control 1 Parietal Ctx   1.9       Control 1 Temporal Ctx   1.4   Control 2 Parietal Ctx   16.3       Control 2 Temporal Ctx   22.8   Control 3 Parietal Ctx   10.0       Control 3 Temporal Ctx   4.8   Control (Path) 1 Parietal   54.0               Ctx       Control 3 Temporal Ctx   1.3   Control (Path) 2 Parietal   11.7               Ctx       Control (Path) 1 Temporal   35.8   Control (Path) 3 Parietal   0.9       Ctx       Ctx       Control (Path) 2 Temporal   15.9   Control (Path) 4 Parietal   27.4       Ctx       Ctx                    
     [0735]               TABLE OC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4295, Run       Ag4295, Run       Tissue Name   222184063   Tissue Name   222184063                                     Adipose   1.2   Renal ca. TK-10   5.7       Melanoma* Hs688(A).T   0.3   Bladder   30.6       Melanoma* Hs688(B).T   0.6   Gastric ca. (liver met.) NCI-   49.3               N87       Melanoma* M14   1.6   Gastric ca. KATO III   92.7       Melanoma* LOXIMVI   0.4   Colon ca. SW-948   16.5       Melanoma* SK-MEL-5   0.7   Colon ca. SW480   8.5       Squamous cell carcinoma   3.2   Colon ca.* (SW480 met)   7.6       SCC-4       SW620       Testis Pool   3.8   Colon ca. HT29   27.5       Prostate ca.* (bone met)   3.5   Colon ca. HCT-116   95.9       PC-3       Prostate Pool   3.8   Colon ca. CaCo-2   40.6       Placenta   1.0   Colon cancer tissue   30.4       Uterus Pool   2.8   Colon ca. SW1116   9.5       Ovarian ca. OVCAR-3   3.8   Colon ca. Colo-205   8.0       Ovarian ca. SK-OV-3   7.0   Colon ca. SW-48   1.6       Ovarian ca. OVCAR-4   6.1   Colon Pool   4.1       Ovarian ca. OVCAR-5   21.9   Small Intestine Pool   3.8       Ovarian ca. IGROV-1   0.6   Stomach Pool   5.3       Ovarian ca. OVCAR-8   2.6   Bone Marrow Pool   1.7       Ovary   3.2   Fetal Heart   0.9       Breast ca. MCF-7   72.2   Heart Pool   1.9       Breast ca. MDA-MB-231   0.9   Lymph Node Pool   5.4       Breast ca. BT 549   1.7   Fetal Skeletal Muscle   0.8       Breast ca. T47D   56.6   Skeletal Muscle Pool   0.2       Breast ca. MDA-N   0.1   Spleen Pool   1.9       Breast Pool   5.6   Thymus Pool   4.0       Trachea   19.6   CNS cancer (glio/astro)   1.1               U87-MG       Lung   1.0   CNS cancer (glio/astro) U-   0.1               118-MG       Fetal Lung   11.0   CNS cancer (neuro; met)   21.8               SK-N-AS       Lung ca. NCI-N417   15.7   CNS cancer (astro) SF-539   0.1       Lung ca. LX-1   8.0   CNS cancer (astro) SNB-75   1.1       Lung ca. NCI-H146   14.9   CNS cancer (glio) SNB-19   0.6       Lung ca. SHP-77   24.3   CNS cancer (glio) SF-295   1.6       Lung ca. A549   5.3   Brain (Amygdala) Pool   12.6       Lung ca. NCI-H526   23.7   Brain (cerebellum)   32.1       Lung ca. NCI-H23   1.9   Brain (fetal)   100.0       Lung ca. NCI-H460   4.2   Brain (Hippocampus) Pool   9.6       Lung ca. HOP-62   0.1   Cerebral Cortex Pool   23.0       Lung ca. NCI-H522   0.9   Brain (Substantia nigra)   15.8               Pool       Liver   0.1   Brain (Thalamus) Pool   25.0       Fetal Liver   1.6   Brain (whole)   27.2       Liver ca. HepG2   4.1   Spinal Cord Pool   6.7       Kidney Pool   4.0   Adrenal Gland   1.9       Fetal Kidney   5.8   Pituitary gland Pool   9.7       Renal ca. 786-0   0.5   Salivary Gland   18.0       Renal ca. A498   1.3   Thyroid (female)   0.6       Renal ca. ACHN   0.0   Pancreatic ca. CAPAN2   4.5       Renal ca. UO-31   0.4   Pancreas Pool   13.2                    
     [0736]               TABLE OD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4295, Run       Ag4295, Run       Tissue Name   181981934   Tissue Name   181981934                                     Secondary Th1 act   0.2   HUVEC IL-1beta   15.3       Secondary Th2 act   1.1   HUVEC IFN gamma   24.1       Secondary Tr1 act   0.0   HUVEC TNF alpha + IFN   11.8               gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha + IL4   15.7       Secondary Th2 rest   0.0   HUVEC IL-11   6.3       Secondary Tr1 rest   0.4   Lung Microvascular EC   23.2               none       Primary Th1 act   2.8   Lung Microvascular EC   19.2               TNF alpha + IL-1beta       Primary Th2 act   0.6   Microvascular Dermal EC   16.0               none       Primary Tr1 act   3.1   Microsvasular Dermal EC   10.8               TNF alpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   1.1               TNF alpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium   0.7               none       Primary Tr1 rest   0.3   Small airway epithelium   0.5               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   1.5   Coronery artery SMC rest   0.0       act       CD45RO CD4 lymphocyte   1.6   Coronery artery SMC   0.7       act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.3   Astrocytes rest   0.5       Secondary CD8 lymphocyte   1.1   Astrocytes TNF alpha + IL-   0.0       rest       1beta       Secondary CD8 lymphocyte   1.5   KU-812 (Basophil) rest   0.3       act       CD4 lymphocyte none   0.3   KU-812 (Basophil)   1.8               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.8   CCD1106 (Keratinocytes)   12.3       CD95 CH11       none       LAK cells rest   4.8   CCD1106 (Keratinocytes)   14.6               TNF alpha + IL-1beta       LAK cells IL-2   1.0   Liver cirrhosis   5.2       LAK cells IL-2 + IL-12   1.6   NCI-H292 none   8.5       LAK cells IL-2 + IFN   1.8   NCI-H292 IL-4   10.5       gamma       LAK cells IL-2 + IL-18   4.7   NCI-H292 IL-9   15.8       LAK cells PMA/ionomycin   5.9   NCI-H292 IL-13   12.6       NK Cells IL-2 rest   1.4   NCI-H292 IFN gamma   26.6       Two Way MLR 3 day   2.6   HPAEC none   12.2       Two Way MLR 5 day   1.9   HPAEC TNF alpha +   22.4               IL-1beta       Two Way MLR 7 day   4.2   Lung fibroblast none   0.0       PBMC rest   3.0   Lung fibroblast   0.6               TNF alpha + IL-1beta       PBMC PWM   0.9   Lung fibroblast IL-4   0.0       PBMC PHA-L   2.0   Lung fibroblast IL-9   1.5       Ramos (B cell) none   0.0   Lung fibroblast IL-13   1.0       Ramos (B cell) ionomycin   0.3   Lung fibroblast IFN gamma   1.0       B lymphocytes PWM   2.8   Dermal fibroblast CCD1070   0.0               rest       B lymphocytes CD40L and   1.1   Dermal fibroblast CCD1070   0.5       IL-4       TNF alpha       EOL-1 dbcAMP   1.5   Dermal fibroblast CCD1070   0.4               IL-1beta       EOL-1 dbcAMP   1.3   Dermal fibroblast IFN   0.4       PMA/ionomycin       gamma       Dendritic cells none   2.4   Dermal fibroblast IL-4   2.4       Dendritic cells LPS   2.2   Dermal Fibroblasts rest   1.1       Dendritic cells anti-CD40   1.6   Neutrophils TNFa + LPS   13.2       Monocytes rest   5.2   Neutrophils rest   9.7       Monocytes LPS   100.0   Colon   1.5       Macrophages rest   17.8   Lung   13.6       Macrophages LPS   10.9   Thymus   4.4       HUVEC none   9.2   Kidney   6.2       HUVEC starved   5.1                    
     [0737] CNS_neurodegeneration_v1.0 Summary: Ag4295 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.  
     [0738] General_screening_panel_v1.4 Summary: Ag4295 Highest expression of this gene is seen in the fetal brain (CT=27.4). Thus, expression of this gene could be used to differentiate between fetal and adult brain tissue. In addition, this gene is expressed at moderate levels in all CNS regions examined. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurological disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0739] This gene is highly expressed in clusters of cell lines derived from colon, gastric, and breast cancers. Thus, expression of this gene could be used as a marker of these cancers. Therapeutic modulation of this gene or gene product may be effective in the treatment of these cancers.  
     [0740] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, fetal skeletal muscle and liver, and adult and fetal heart. This expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0741] Panel 4.1D Summary: Ag4295 Highest expression of this gene is seen in LPS treated monocytes (CT=30). Low levels of expression are also seen in many samples on this panel, including LPS treated macrophages, treated and untreated HUVECs, NCI-H292 cells, HPAECs, activated neutrophils, and normal lung. The expression of this transcript in LPS treated monocytes, cells that play a crucial role in linking innate immunity to adaptive immunity, suggests a role for this gene product in initiating inflammatory reactions. Therefore, modulation of the expression or activity of this gene through the application of monoclonal antibodies may reduce or prevent early stages of inflammation and reduce the severity of inflammatory diseases such as psoriasis, asthma, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and other lung inflammatory diseases.  
     P. CG105778-01: PEFLIN Like Protein  
     [0742] Expression of gene CG105778-01 was assessed using the primer-probe set Ag4320, described in Table PA. Results of the RTQ-PCR runs are shown in Tables PB, PC and PD.  
               TABLE PA                          Probe Name Ag4320                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-cacctccaaattcctacggt-3′   20   285   134               Probe   TET-5′-ctcatggacagggtggctcccct-3′-TAMRA   23   321   135               Reverse   5′-caggagtaggcctcatccat-3′   20   350   136                  
 
     [0743]               TABLE PB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4320, Run       Ag4320, Run       Tissue Name   224075257   Tissue Name   224075257                                     AD 1 Hippo   13.6   Control (Path) 3 Temporal   3.0               Ctx       AD 2 Hippo   13.3   Control (Path) 4 Temporal   76.8               Ctx       AD 3 Hippo   8.0   AD 1 Occipital Ctx   13.2       AD 4 Hippo   9.5   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   80.7   AD 3 Occipital Ctx   0.0       AD 6 Hippo   81.8   AD 4 Occipital Ctx   12.8       Control 2 Hippo   7.5   AD 5 Occipital Ctx   22.7       Control 4 Hippo   14.2   AD 6 Occipital Ctx   47.6       Control (Path) 3 Hippo   7.0   Control 1 Occipital Ctx   6.0       AD 1 Temporal Ctx   25.2   Control 2 Occipital Ctx   58.6       AD 2 Temporal Ctx   33.2   Control 3 Occipital Ctx   0.0       AD 3 Temporal Ctx   17.3   Control 4 Occipital Ctx   12.9       AD 4 Temporal Ctx   40.1   Control (Path) 1 Occipital   60.3               Ctx       AD 5 Inf Temporal Ctx   82.4   Control (Path) 2 Occipital   12.9               Ctx       AD 5 Sup Temporal Ctx   81.8   Control (Path) 3 Occipital   5.7               Ctx       AD 6 Inf Temporal Ctx   53.6   Control (Path) 4 Occipital   0.0               Ctx       AD 6 Sup Temporal Ctx   100.0   Control 1 Parietal Ctx   0.0       Control 1 Temporal Ctx   4.9   Control 2 Parietal Ctx   69.7       Control 2 Temporal Ctx   14.7   Control 3 Parietal Ctx   26.6       Control 3 Temporal Ctx   0.7   Control (Path) 1 Parietal   57.0               Ctx       Control 3 Temporal Ctx   10.3   Control (Path) 2 Parietal   48.3               Ctx       Control (Path) 1 Temporal   42.9   Control (Path) 3 Parietal   10.3       Ctx       Ctx       Control (Path) 2 Temporal   21.5   Control (Path) 4 Parietal   34.2       Ctx       Ctx                    
     [0744]               TABLE PC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4320, Run       Ag4320, Run       Tissue Name   222523502   Tissue Name   222523502                                     Adipose   4.1   Renal ca. TK-10   27.4       Melanoma* Hs688(A).T   11.8   Bladder   30.6       Melanoma* Hs688(B).T   11.6   Gastric ca. (liver met.) NCI-   43.8               N87       Melanoma* M14   11.2   Gastric ca. KATO III   30.6       Melanoma* LOXIMVI   6.6   Colon ca. SW-948   3.3       Melanoma* SK-MEL-5   27.0   Colon ca. SW480   13.4       Squamous cell carcinoma   2.3   Colon ca.* (SW480 met)   16.6       SCC-4       SW620       Testis Pool   3.3   Colon ca. HT29   6.7       Prostate ca.* (bone met)   27.0   Colon ca. HCT-116   35.4       PC-3       Prostate Pool   6.3   Colon ca. CaCo-2   16.8       Placenta   7.7   Colon cancer tissue   20.4       Uterus Pool   1.4   Colon ca. SW1116   4.7       Ovarian ca. OVCAR-3   42.0   Colon ca. Colo-205   8.0       Ovarian ca. SK-OV-3   50.3   Colon ca. SW-48   3.8       Ovarian ca. OVCAR-4   12.2   Colon Pool   5.0       Ovarian ca. OVCAR-5   41.8   Small Intestine Pool   25.5       Ovarian ca. IGROV-1   23.5   Stomach Pool   17.9       Ovarian ca. OVCAR-8   26.8   Bone Marrow Pool   9.5       Ovary   11.1   Fetal Heart   13.0       Breast ca. MCF-7   62.4   Heart Pool   6.2       Breast ca. MDA-MB-231   34.4   Lymph Node Pool   22.5       Breast ca. BT 549   52.1   Fetal Skeletal Muscle   2.7       Breast ca. T47D   100.0   Skeletal Muscle Pool   5.7       Breast ca. MDA-N   17.4   Spleen Pool   21.0       Breast Pool   10.9   Thymus Pool   54.0       Trachea   18.4   CNS cancer (glio/astro)   24.7               U87-MG       Lung   11.0   CNS cancer (glio/astro) U-   30.4               118-MG       Fetal Lung   55.5   CNS cancer (neuro; met)   94.6               SK-N-AS       Lung ca. NCI-N417   7.2   CNS cancer (astro) SF-539   16.5       Lung ca. LX-1   14.1   CNS cancer (astro) SNB-75   46.3       Lung ca. NCI-H146   5.5   CNS cancer (glio) SNB-19   15.8       Lung ca. SHP-77   49.3   CNS cancer (glio) SF-295   25.7       Lung ca. A549   17.2   Brain (Amygdala) Pool   5.0       Lung ca. NCI-H526   3.3   Brain (cerebellum)   16.4       Lung ca. NCI-H23   47.0   Brain (fetal)   20.9       Lung ca. NCI-H460   48.6   Brain (Hippocampus) Pool   9 8       Lung ca. HOP-62   12.6   Cerebral Cortex Pool   8.5       Lung ca. NCI-H522   26.4   Brain (Substantia nigra)   9.0               Pool       Liver   0.0   Brain (Thalamus) Pool   16.2       Fetal Liver   14.7   Brain (whole)   5.8       Liver ca. HepG2   12.1   Spinal Cord Pool   9.3       Kidney Pool   49.7   Adrenal Gland   13.4       Fetal Kidney   25.3   Pituitary gland Pool   5.3       Renal ca. 786-0   16.7   Salivary Gland   4.4       Renal ca. A498   5.2   Thyroid (female)   2.4       Renal ca. ACHN   10.5   Pancreatic ca. CAPAN2   30.8       Renal ca. UO-31   6.7   Pancreas Pool   18.4                    
     [0745]               TABLE PD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4320, Run       Ag4320, Run       Tissue Name   182392272   Tissue Name   182392272                                     Secondary Th1 act   13.7   HUVEC IL-1beta   3.1       Secondary Th2 act   15.8   HUVEC IFN gamma   4.5       Secondary Tr1 act   31.9   HUVEC TNF alpha + IFN   2.5               gamma       Secondary Th1 rest   2.5   HUVEC TNF alpha + IL4   6.2       Secondary Th2 rest   9.9   HUVEC IL-11   3.1       Secondary Tr1 rest   23.2   Lung Microvascular EC   11.3               none       Primary Th1 act   19.5   Lung Microvascular EC   6.0               TNF alpha + IL-1beta       Primary Th2 act   20.7   Microvascular Dermal EC   2.8               none       Primary Tr1 act   20.4   Microsvasular Dermal EC   5.1               TNF alpha + IL-1beta       Primary Th1 rest   18.4   Bronchial epithelium   7.0               TNF alpha + IL1beta       Primary Th2 rest   12.5   Small airway epithelium   1.1               none       Primary Tr1 rest   13.8   Small airway epithelium   4.0               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   2.8   Coronery artery SMC rest   0.0       act       CD45RO CD4 lymphocyte   21.0   Coronery artery SMC   0.0       act       TNF alpha + IL-1beta       CD8 lymphocyte act   34.4   Astrocytes rest   1.5       Secondary CD8 lymphocyte   21.5   Astrocytes TNF alpha + IL-   2.4       rest       1beta       Secondary CD8 lymphocyte   8.8   KU-812 (Basophil) rest   11.6       act       CD4 lymphocyte none   18.8   KU-812 (Basophil)   23.3               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   15.5   CCD1106 (Keratinocytes)   3.5       CH11       none       LAK cells rest   25.0   CCD1106 (Keratinocytes)   3.0               TNF alpha + IL-1beta       LAK cells IL-2   8.9   Liver cirrhosis   13.2       LAK cells IL-2 + IL-12   17.6   NCI-H292 none   9.4       LAK cells IL-2 + IFN gamma   17.4   NCI-H292 IL-4   11.2       LAK cells IL-2 + IL-18   10.4   NCI-H292 IL-9   6.9       LAK cells PMA/ionomycin   21.5   NCI-H292 IL-13   6.8       NK Cells IL-2 rest   26.2   NCI-H292 IFN gamma   5.4       Two Way MLR 3 day   23.2   HPAEC none   0.7       Two Way MLR 5 day   6.4   HPAEC TNF alpha +   19.1               IL-1beta       Two Way MLR 7 day   16.0   Lung fibroblast none   3.4       PBMC rest   30.8   Lung fibroblast   2.4               TNF alpha + IL-1beta       PBMC PWM   15.2   Lung fibroblast IL-4   1.4       PBMC PHA-L   13.3   Lung fibroblast IL-9   4.6       Ramos (B cell) none   17.7   Lung fibroblast IL-13   10.1       Ramos (B cell) ionomycin   12.0   Lung fibroblast IFN gamma   4.8       B lymphocytes PWM   11.8   Dermal fibroblast CCD1070   8.8               rest       B lymphocytes CD40L and   31.0   Dermal fibroblast CCD1070   15.1       IL-4       TNF alpha       EOL-1 dbcAMP   21.6   Dermal fibroblast CCD1070   0.0               IL-1beta       EOL-1 dbcAMP   31.2   Dermal fibroblast IFN   2.6       PMA/ionomycin       gamma       Dendritic cells none   8.9   Dermal fibroblast IL-4   8.3       Dendritic cells LPS   3.5   Dermal Fibroblasts rest   1.3       Dendritic cells anti-CD40   8.0   Neutrophils TNFa + LPS   12.7       Monocytes rest   70.7   Neutrophils rest   17.8       Monocytes LPS   25.9   Colon   9.5       Macrophages rest   14.9   Lung   9.7       Macrophages LPS   8.7   Thymus   99.3       HUVEC none   3.0   Kidney   100.0       HUVEC starved   5.9                    
     [0746] CNS_neurodegeneration_v1.0 Summary: Ag4320 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.  
     [0747] General_screening_panel_v1.4 Summary: Ag4320 This gene is widely expressed in this panel, with highest expression in a breast cancer cell line (CT=30.2). Prominent levels of expression are also seen in brain, lung, and ovarian cancer cell lines. This widespread expression suggests that this gene is involved in cell growth. Therapeutic modulation of the expression or function of this protein may be useful in the treatment of these cancers.  
     [0748] This gene is also expressed at low but significant levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0749] Among tissues with metabolic function, this gene is expressed at low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, skeletal muscle, fetal liver and adult and fetal heart. This expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0750] Panel 4.1D Summary: Ag4320 Highest expression is seen in the thymus and kidney (CTs=31). Low but significant levels of expression are also seen in many other samples on this panel including members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     Q. CG105796-01: Novel Neurotransmitter-gated Ion-channel  
     [0751] Expression of gene CG105796-01 was assessed using the primer-probe set Ag4307, described in Table QA. Results of the RTQ-PCR runs are shown in Table QB.  
               TABLE QA                          Probe Name Ag4307                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-gagctgagacctctccttgaag-3′   22   1000   137               Probe   TET-5′-agaccaggagccagctgccagct-3′-TAMRA   23   1026   138               Reverse   5′-caagagtgcaaggtttctctga-3′   22   1069   139                  
 
     [0752]               TABLE QB                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4307, Run       Ag4307, Run       Tissue Name   182243415   Tissue Name   182243415                                     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   0.1               gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha + IL4   0.1       Secondary Th2 rest   0.1   HUVEC IL-11   0.0       Secondary Tr1 rest   0.0   Lung Microvascular EC none   0.4       Primary Th1 act   0.0   Lung Microvascular EC   0.1               TNF alpha + IL-1beta       Primary Th2 act   0.0   Microvascular Dermal EC   0.0               none       Primary Tr1 act   0.0   Microsvasular Dermal EC   0.0               TNF alpha + IL-1beta       Primary Th1 rest   0.1   Bronchial epithelium   0.0               TNF alpha + IL1beta       Primary Th2 rest   0.1   Small airway epithelium none   0.0       Primary Tr1 rest   0.2   Small airway epithelium   0.0               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   0.1   Coronery artery SMC rest   0.0       act       CD45RO CD4 lymphocyte   0.1   Coronery artery SMC   0.0       act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   0.0       Secondary CD8 lymphocyte   0.1   Astrocytes TNF alpha + IL-   0.0       rest       1beta       Secondary CD8 lymphocyte   0.2   KU-812 (Basophil) rest   0.0       act       CD4 lymphocyte none   0.2   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   0.2   CCD1106 (Keratinocytes)   0.0       CD95 CH11       none       LAK cells rest   0.0   CCD1106 (Keratinocytes)   0.0               TNF alpha + IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   0.0       LAK cells IL-2 + IL-12   0.0   NCI-H292 none   0.0       LAK cells IL-2 + IFN   0.1   NCI-H292 IL-4   0.0       gamma       LAK cells IL-2 + IL-18   0.1   NCI-H292 IL-9   0.0       LAK cells PMA/ionomycin   0.0   NCI-H292 IL-13   0.0       NK Cells IL-2 rest   2.8   NCI-H292 IFN gamma   0.0       Two Way MLR 3 day   0.3   HPAEC none   0.1       Two Way MLR 5 day   0.0   HPAEC TNF alpha +   0.1               IL-1beta       Two Way MLR 7 day   0.0   Lung fibroblast none   0.0       PBMC rest   0.1   Lung fibroblast TNF alpha +   0.2               IL-1beta       PBMC PWM   0.0   Lung fibroblast IL-4   0.1       PBMC PHA-L   0.0   Lung fibroblast IL-9   0.0       Ramos (B cell) none   0.0   Lung fibroblast IL-13   0.1       Ramos (B cell) ionomycin   0.0   Lung fibroblast IFN gamma   0.0       B lymphocytes PWM   0.0   Dermal fibroblast CCD1070   0.1               rest       B lymphocytes CD40L and   0.1   Dermal fibroblast CCD1070   0.6       IL-4       TNF alpha       EOL-1 dbcAMP   1.6   Dermal fibroblast CCD1070   0.0               IL-1beta       EOL-1 dbcAMP   0.1   Dermal fibroblast IFN   0.1       PMA/ionomycin       gamma       Dendritic cells none   0.0   Dermal fibroblast IL-4   0.5       Dendritic cells LPS   0.1   Dermal Fibroblasts rest   1.0       Dendritic cells anti-CD40   0.1   Neutrophils TNFa + LPS   1.1       Monocytes rest   0.7   Neutrophils rest   2.1       Monocytes LPS   0.2   Colon   2.5       Macrophages rest   0.0   Lung   3.6       Macrophages LPS   0.1   Thymus   14.0       HUVEC none   0.0   Kidney   100.0       HUVEC starved   0.1                    
     [0753] Panel 4.1D Summary: Ag4307 Highest expression of this gene is seen in kidney (CT=27.9). Thus, expression of this gene could be used to differentiate the kidney derived sample from other samples on this panel and as a marker of kidney tissue. In addition, therapeutic targeting of the expression or function of this gene may modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.  
     R. CG106002-01: Carboxyl-Terminal PDZ Ligand of Neuronal Nitric Oxide Synthase  
     [0754] Expression of gene CG 106002-01 was assessed using the primer-probe set Ag4315, described in Table RA. Results of the RTQ-PCR runs are shown in Tables RB, RC and RD.  
               TABLE RA                          Probe Name Ag4315                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-gaccccatctacaggatcttct-3′   22   718   141               Probe   TET-5′-tgtctctcatgattcccaagacttga-3′-TAMRA   26   741   142               Reverse   5′-catctcgagcgatatagctgaa-3′   22   772   143                  
 
     [0755]               TABLE RB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4315, Run       Ag4315, Run       Tissue Name   224074858   Tissue Name   224074858                                     AD 1 Hippo   12.3   Control (Path) 3 Temporal   2.1               Ctx       AD 2 Hippo   34.2   Control (Path) 4 Temporal   25.7               Ctx       AD 3 Hippo   7.6   AD 1 Occipital Ctx   14.9       AD 4 Hippo   5.6   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   90.8   AD 3 Occipital Ctx   3.4       AD 6 Hippo   57.4   AD 4 Occipital Ctx   12.8       Control 2 Hippo   38.2   AD 5 Occipital Ctx   17.6       Control 4 Hippo   3.5   AD 6 Occipital Ctx   46.7       Control (Path) 3 Hippo   3.1   Control 1 Occipital Ctx   0.7       AD 1 Temporal Ctx   9.5   Control 2 Occipital Ctx   55.1       AD 2 Temporal Ctx   26.1   Control 3 Occipital Ctx   12.3       AD 3 Temporal Ctx   4.5   Control 4 Occipital Ctx   2.7       AD 4 Temporal Ctx   15.3   Control (Path) 1 Occipital   76.3               Ctx       AD 5 Inf Temporal Ctx   100.0   Control (Path) 2 Occipital   9.4               Ctx       AD 5 SupTemporal Ctx   45.1   Control (Path) 3 Occipital   1.0               Ctx       AD 6 Inf Temporal Ctx   61.6   Control (Path) 4 Occipital   16.2               Ctx       AD 6 Sup Temporal Ctx   59.5   Control 1 Parietal Ctx   2.3       Control 1 Temporal Ctx   2.0   Control 2 Parietal Ctx   35.1       Control 2 Temporal Ctx   28.3   Control 3 Parietal Ctx   13.9       Control 3 Temporal Ctx   13.3   Control (Path) 1 Parietal   54.3               Ctx       Control 4 Temporal Ctx   4.4   Control (Path) 2 Parietal   23.0               Ctx       Control (Path) 1 Temporal Ctx   64.6   Control (Path) 3 Parietal   0.8               Ctx       Control (Path) 2 Temporal Ctx   39.8   Control (Path) 4 Parietal   42.9               Ctx                    
     [0756]               TABLE RC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4315, Run       Ag4315, Run       Tissue Name   222364258   Tissue Name   222364258                                     Adipose   4.6   Renal ca. TK-10   31.9       Melanoma* Hs688(A).T   0.1   Bladder   7.6       Melanoma* Hs688(B).T   0.3   Gastric ca. (liver met.)   38.4               NCI-N87       Melanoma* M14   0.9   Gastric ca. KATO III   22.5       Melanoma* LOXIMVI   0.2   Colon ca. SW-948   9.4       Melanoma* SK-MEL-5   32.1   Colon ca. SW480   23.3       Squamous cell carcinoma   2.6   Colon ca.* (SW480 met)   9.3       SCC-4       SW620       Testis Pool   3.6   Colon ca. HT29   5.7       Prostate ca.* (bone met) PC-3   5.9   Colon ca. HCT-116   19.8       Prostate Pool   3.4   Colon ca. CaCo-2   17.8       Placenta   5.2   Colon cancer tissue   8.1       Uterus Pool   1.0   Colon ca. SW1116   1.9       Ovarian ca. OVCAR-3   4.8   Colon ca. Colo-205   6.6       Ovarian ca. SK-OV-3   24.0   Colon ca. SW-48   5.6       Ovarian ca. OVCAR-4   1.6   Colon Pool   3.8       Ovarian ca. OVCAR-5   58.6   Small Intestine Pool   3.9       Ovarian ca. IGROV-1   23.7   Stomach Pool   3.3       Ovarian ca. OVCAR-8   8.0   Bone Marrow Pool   2.4       Ovary   7.3   Fetal Heart   3.6       Breast ca. MCF-7   28.9   Heart Pool   2.8       Breast ca. MDA-MB-231   10.9   Lymph Node Pool   6.6       Breast ca. BT 549   2.7   Fetal Skeletal Muscle   0.7       Breast ca. T47D   92.7   Skeletal Muscle Pool   0.6       Breast ca. MDA-N   8.0   Spleen Pool   1.2       Breast Pool   6.5   Thymus Pool   3.3       Trachea   15.6   CNS cancer (glio/astro)   9.5               U87-MG       Lung   0.9   CNS cancer (glio/astro) U-   1.0               118-MG       Fetal Lung   9.6   CNS cancer (neuro; met)   0.2               SK-N-AS       Lung ca. NCI-N417   6.4   CNS cancer (astro) SF-539   0.7       Lung ca. LX-1   6.1   CNS cancer (astro) SNB-75   6.2       Lung ca. NCI-H146   10.7   CNS cancer (glio) SNB-19   24.5       Lung ca. SHP-77   3.8   CNS cancer (glio) SF-295   17.8       Lung ca. A549   0.1   Brain (Amygdala) Pool   16.7       Lung ca. NCI-H526   5.9   Brain (cerebellum)   100.0       Lung ca. NCI-H23   2.1   Brain (fetal)   35.8       Lung ca. NCI-H460   1.3   Brain (Hippocampus) Pool   18.9       Lung ca. HOP-62   0.5   Cerebral Cortex Pool   24.7       Lung ca. NCI-H522   3.3   Brain (Substantia nigra)   21.2               Pool       Liver   5.2   Brain (Thalamus) Pool   34.2       Fetal Liver   13.8   Brain (whole)   28.5       Liver ca. HepG2   21.3   Spinal Cord Pool   11.7       Kidney Pool   9.4   Adrenal Gland   10.9       Fetal Kidney   15.5   Pituitary gland Pool   1.9       Renal ca. 786-0   1.8   Salivary Gland   12.7       Renal ca. A498   3.7   Thyroid (female)   0.6       Renal ca. ACHN   5.8   Pancreatic ca. CAPAN2   23.5       Renal ca. UO-31   3.8   Pancreas Pool   5.1                    
     [0757]               TABLE RD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4315, Run       Ag4315, Run       Tissue Name   182244231   Tissue Name   182244231                                     Secondary Th1 act   1.1   HUVEC IL-1 beta   36.1       Secondary Th2 act   0.0   HUVEC IFN gamma   29.3       Secondary Tr1 act   0.0   HUVEC TNF alpha + IFN   11.5               gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha + IL4   9.0       Secondary Th2 rest   0.0   HUVEC IL-11   29.1       Secondary Tr1 rest   0.0   Lung Microvascular EC   30.6               none       Primary Th1 act   0.0   Lung Microvascular EC   13.1               TNF alpha + IL-1 beta       Primary Th2 act   0.9   Microvascular Dermal EC   61.1               none       Primary Tr1 act   1.8   Microsvasular Dermal EC   11.0               TNF alpha + IL-1 beta       Primary Th1 rest   0.0   Bronchial epithelium   4.0               TNF alpha + IL1 beta       Primary Th2 rest   0.0   Small airway epithelium   2.0               none       Primary Tr1 rest   0.0   Small airway epithelium   4.6               TNF alpha + IL-1 beta       CD45RA CD4 lymphocyte act   3.3   Coronery artery SMC rest   0.0       CD45RO CD4 lymphocyte act   0.9   Coronery artery SMC   0.0               TNF alpha + IL-1 beta       CD8 lymphocyte act   0.0   Astrocytes rest   55.1       Secondary CD8 lymphocyte   3.4   Astrocytes TNF alpha + IL-   11.9       rest       1 beta       Secondary CD8 lymphocyte   0.0   KU-812 (Basophil) rest   8.0       act       CD4 lymphocyte none   0.0   KU-812 (Basophil)   13.8               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   0.0   CCD1106 (Keratinocytes)   5.8       CH11       none       LAK cells rest   1.5   CCD1106 (Keratinocytes)   11.4               TNF alpha + IL-1 beta       LAK cells IL-2   2.3   Liver cirrhosis   28.7       LAK cells IL-2 + IL-12   0.0   NCI-H292 none   33.2       LAK cells IL-2 + IFN gamma   0.0   NCI-H292 IL-4   29.3       LAK cells IL-2 + IL-18   0.9   NCI-H292 IL-9   82.4       LAK cells PMA/ionomycin   2.1   NCI-H292 IL-13   33.9       NK Cells IL-2 rest   0.0   NCI-H292 IFN gamma   36.9       Two Way MLR 3 day   1.9   HPAEC none   58.6       Two Way MLR 5 day   2.7   HPAEC TNF alpha + IL-1   15.3               beta       Two Way MLR 7 day   1.8   Lung fibroblast none   0.0       PBMC rest   0.9   Lung fibroblast TNF alpha +   0.0               IL-1 beta       PBMC PWM   1.9   Lung fibroblast IL-4   1.3       PBMC PHA-L   1.9   Lung fibroblast IL-9   1.6       Ramos (B cell) none   0.0   Lung fibroblast IL-13   3.9       Ramos (B cell) ionomycin   0.0   Lung fibroblast IFN   2.1               gamma       B lymphocytes PWM   0.8   Dermal fibroblast   0.0               CCD1070 rest       B lymphocytes CD40L and   3.6   Dermal fibroblast   3.4       IL-4       CCD1070 TNF alpha       EOL-1 dbcAMP   51.8   Dermal fibroblast   2.3               CCD1070 IL-1 beta       EOL-1 dbcAMP   4.7   Dermal fibroblast IFN   5.4       PMA/ionomycin       gamma       Dendritic cells none   8.0   Dermal fibroblast IL-4   0.0       Dendritic cells LPS   2.0   Dermal Fibroblasts rest   7.3       Dendritic cells anti-CD40   0.0   Neutrophils TNFa + LPS   1.7       Monocytes rest   0.0   Neutrophils rest   1.8       Monocytes LPS   4.9   Colon   27.2       Macrophages rest   100.0   Lung   17.0       Macrophages LPS   6.6   Thymus   18.9       HUVEC none   28.5   Kidney   94.6       HUVEC starved   20.0                    
     [0758] CNS_neurodegeneration_v1.0 Summary: Ag4315 This panel confirms the expression of this gene at moderate levels in the brain in an independent group of individuals. This gene is upregulated in the temporal cortex of Alzheimer&#39;s disease patients when compared with non-demented controls. Therefore, therapeutic modulation fo the expression or function of this gene may slow or stop the progression of Alzheimer&#39;s disease.  
     [0759] General_screening_panel_v1.4 Summary: Ag4315 Highest expression of this gene is seen in the cerebellum (CT=28). Moderate levels of expression are seen throughout the CNS. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurological disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0760] Prominent levels of expression are seen in clusters of cell lines derived from breast and ovarian cancer cell lines. Moderate levels of expression are also detected in samples from pancreatic, brain, renal, lung, melanoma, colon and gastric cancers. Thus, expression of this gene could be used as a marker of breast and ovarian cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of these cancers.  
     [0761] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal heart and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0762] Panel 4.1D Summary: Ag4315 Highest expression is seen in resting macrophages (CT=32.4). Low but significant levels of expression are seen in kidney, untreated HPAECs, untreated astrocytes, and treated and untreated NCI-H292 cells. In addition, this protein encoded by this gene is down regulated in macrophages after LPS stimulation. Therefore, this gene product may respond to inflammatory stimuli and become down regulated after 12-24 hr exposure. Thus, therapeutics designed against this putative protein may reduce or inhibit inflammation in diseases such as asthma, IBD, psoriasis, arthritis and allergy. Furthermore, agonistic therapeutics designed with this protein product may stimulate/provoke the immune response and improve the efficacy of vaccines and antiviral or antibacterial treatments.  
     S. CG106868-01: Amyloid Beta A4 Precursor Protein-Binding Family B Member 2  
     [0763] Expression of gene CG106868-01 was assessed using the primer-probe set Ag4327, described in Table SA. Results of the RTQ-PCR runs are shown in Tables SB, SC and SD.  
               TABLE SA                          Probe Name Ag4327                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tatactgatgccaacagccaat-3′   22   269   144               Probe   TET-5′-tgtcaaccaacaggttcaattttatga-3′-TAMRA   27   293   145               Reverse   5′-aaataggatggcgagtttgtg-3′   21   330   146                  
 
     [0764]               TABLE SB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4327, Run       Ag4327, Run       Tissue Name   224344076   Tissue Name   224344076                                     AD 1 Hippo   12.8   Control (Path) 3 Temporal   6.0               Ctx       AD 2 Hippo   24.1   Control (Path) 4 Temporal   28.1               Ctx       AD 3 Hippo   8.2   AD 1 Occipital Ctx   20.0       AD 4 Hippo   6.8   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   92.0   AD 3 Occipital Ctx   8.7       AD 6 Hippo   54.7   AD 4 Occipital Ctx   17.3       Control 2 Hippo   21.9   AD 5 Occipital Ctx   32.3       Control 4 Hippo   9.2   AD 6 Occipital Ctx   26.4       Control (Path) 3 Hippo   9.5   Control 1 Occipital Ctx   5.6       AD 1 Temporal Ctx   18.4   Control 2 Occipital Ctx   48.6       AD 2 Temporal Ctx   26.8   Control 3 Occipital Ctx   16.2       AD 3 Temporal Ctx   6.9   Control 4 Occipital Ctx   6.8       AD 4 Temporal Ctx   21.0   Control (Path) 1 Occipital   84.1               Ctx       AD 5 Inf Temporal Ctx   100.0   Control (Path) 2 Occipital   14.7               Ctx       AD 5 Sup Temporal Ctx   50.3   Control (Path) 3 Occipital   5.4               Ctx       AD 6 Inf Temporal Ctx   72.7   Control (Path) 4 Occipital   19.6               Ctx       AD 6 Sup Temporal Ctx   57.4   Control 1 Parietal Ctx   7.4       Control 1 Temporal Ctx   5.4   Control 2 Parietal Ctx   47.3       Control 2 Temporal Ctx   31.9   Control 3 Parietal Ctx   15.5       Control 3 Temporal Ctx   17.8   Control (Path) 1 Parietal Ctx   68.3       Control 3 Temporal Ctx   6.0   Control (Path) 2 Parietal Ctx   29.1       Control (Path) 1 Temporal   42.3   Control (Path) 3 Parietal Ctx   5.4       Ctx       Control (Path) 2 Temporal   28.9   Control (Path) 4 Parietal Ctx   37.9       Ctx                    
     [0765]               TABLE SC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4327, Run       Ag4327, Run       Tissue Name   222550477   Tissue Name   222550477                                     Adipose   20.9   Renal ca. TK-10   13.7       Melanoma* Hs688(A).T   32.1   Bladder   18.0       Melanoma* Hs688(B).T   29.5   Gastric ca. (liver met.) NCI-   24.3               N87       Melanoma* M14   0.7   Gastric ca. KATO III   46.0       Melanoma* LOXIMVI   44.4   Colon ca. SW-948   9.5       Melanoma* SK-MEL-5   9.9   Colon ca. SW480   61.6       Squamous cell carcinoma   6.4   Colon ca.* (SW480 met)   26.4       SCC-4       SW620       Testis Pool   6.7   Colon ca. HT29   2.4       Prostate ca.* (bone met)   47.3   Colon ca. HCT-116   51.1       PC-3       Prostate Pool   5.1   Colon ca. CaCo-2   25.2       Placenta   4.2   Colon cancer tissue   15.1       Uterus Pool   5.3   Colon ca. SW1116   3.1       Ovarian ca. OVCAR-3   14.5   Colon ca. Colo-205   1.8       Ovarian ca. SK-OV-3   26.6   Colon ca. SW-48   11.7       Ovarian ca. OVCAR-4   4.9   Colon Pool   12.9       Ovarian ca. OVCAR-5   30.4   Small Intestine Pool   12.5       Ovarian ca. IGROV-1   13.9   Stomach Pool   11.0       Ovarian ca. OVCAR-8   19.2   Bone Marrow Pool   6.0       Ovary   17.3   Fetal Heart   5.8       Breast ca. MCF-7   100.0   Heart Pool   7.2       Breast ca. MDA-MB-231   61.6   Lymph Node Pool   15.4       Breast ca. BT 549   12.9   Fetal Skeletal Muscle   6.7       Breast ca. T47D   52.1   Skeletal Muscle Pool   7.0       Breast ca. MDA-N   6.8   Spleen Pool   14.0       Breast Pool   11.8   Thymus Pool   11.0       Trachea   13.3   CNS cancer (glio/astro)   46.0               U87-MG       Lung   5.4   CNS cancer (glio/astro) U-   16.5               118-MG       Fetal Lung   41.8   CNS cancer (neuro;met) SK-   5.0               N-AS       Lung ca. NCI-N417   1.6   CNS cancer (astro) SF-539   10.3       Lung ca. LX-1   22.5   CNS cancer (astro) SNB-75   29.3       Lung ca. NCI-H146   20.3   CNS cancer (glio) SNB-19   14.7       Lung ca. SHP-77   8.2   CNS cancer (glio) SF-295   60.7       Lung ca. A549   9.2   Brain (Amygdala) Pool   20.9       Lung ca. NCI-H526   34.6   Brain (cerebellum)   6.3       Lung ca. NCI-H23   31.2   Brain (fetal)   27.4       Lung ca. NCI-H460   10.7   Brain (Hippocampus) Pool   21.5       Lung ca. HOP-62   28.1   Cerebral Cortex Pool   21.8       Lung ca. NCI-H522   96.6   Brain (Substantia nigra)   15.8               Pool       Liver   1.1   Brain (Thalamus) Pool   29.9       Fetal Liver   8.8   Brain (whole)   20.6       Liver ca. HepG2   7.3   Spinal Cord Pool   27.7       Kidney Pool   35.6   Adrenal Gland   7.2       Fetal Kidney   17.6   Pituitary gland Pool   2.8       Renal ca. 786-0   30.1   Salivary Gland   1.9       Renal ca. A498   6.8   Thyroid (female)   11.2       Renal ca. ACHN   13.9   Pancreatic ca. CAPAN2   27.9       Renal ca. UO-31   20.4   Pancreas Pool   15.9                    
     [0766]               TABLE SD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4327, Run       Ag4327, Run       Tissue Name   183714654   Tissue Name   183714654                                     Secondary Th1 act   73.7   HUVEC IL-1 beta   66.4       Secondary Th2 act   13.4   HUVEC IFN gamma   56.6       Secondary Tr1 act   18.6   HUVEC TNF alpha + IFN   35.6               gamma       Secondary Th1 rest   1.3   HUVEC TNF alpha + IL4   52.1       Secondary Th2 rest   0.4   HUVEC IL-11   27.7       Secondary Tr1 rest   0.3   Lung Microvascular EC   81.8               none       Primary Th1 act   3.3   Lung Microvascular EC   56.6               TNF alpha + IL-1 beta       Primary Th2 act   0.4   Microvascular Dermal EC   40.6               none       Primary Tr1 act   0.9   Microsvasular Dermal EC   28.9               TNF alpha + IL-1 beta       Primary Th1 rest   0.1   Bronchial epithelium   20.7               TNF alpha + IL1 beta       Primary Th2 rest   0.0   Small airway epithelium   5.9               none       Primary Tr1 rest   0.0   Small airway epithelium   16.4               TNF alpha + IL-1 beta       CD45RA CD4 lymphocyte   11.8   Coronery artery SMC rest   27.4       act       CD45RO CD4 lymphocyte   0.1   Coronery artery SMC   43.2       act       TNF alpha + IL-1 beta       CD8 lymphocyte act   0.2   Astrocytes rest   11.5       Secondary CD8 lymphocyte   0.0   Astrocytes TNF alpha + IL-   12.5       rest       1 beta       Secondary CD8 lymphocyte   0.4   KU-812 (Basophil) rest   0.0       act       CD4 lymphocyte none   0.0   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   0.1   CCD1106 (Keratinocytes)   21.0       CH11       none       LAK cells rest   1.3   CCD1106 (Keratinocytes)   24.8               TNF alpha + IL-1 beta       LAK cells IL-2   2.1   Liver cirrhosis   9.9       LAK cells IL-2 + IL-12   2.2   NCI-H292 none   7.4       LAK cells IL-2 + IFN gamma   1.6   NCI-H292 IL-4   15.6       LAK cells IL-2 + IL-18   2.1   NCI-H292 IL-9   9.1       LAK cells PMA/ionomycin   0.4   NCI-H292 IL-13   16.6       NK Cells IL-2 rest   1.5   NCI-H292 IFN gamma   9.0       Two Way MLR 3 day   2.4   HPAEC none   43.5       Two Way MLR 5 day   3.6   HPAEC TNF alpha + IL-1   100.0               beta       Two Way MLR 7 day   3.7   Lung fibroblast none   15.6       PBMC rest   0.2   Lung fibroblast TNF alpha +   10.0               IL-1 beta       PBMC PWM   2.1   Lung fibroblast IL-4   9.9       PBMC PHA-L   0.7   Lung fibroblast IL-9   27.9       Ramos (B cell) none   27.0   Lung fibroblast IL-13   11.9       Ramos (B cell) ionomycin   47.3   Lung fibroblast IFN gamma   22.1       B lymphocytes PWM   1.6   Dermal fibroblast CCD1070   17.8               rest       B lymphocytes CD40L and   1.1   Dermal fibroblast CCD1070   14.2       IL-4       TNF alpha       EOL-1 dbcAMP   0.8   Dermal fibroblast CCD1070   17.6               IL-1 beta       EOL-1 dbcAMP   3.4   Dermal fibroblast IFN   10.7       PMA/ionomycin       gamma       Dendritic cells none   8.0   Dermal fibroblast IL-4   27.0       Dendritic cells LPS   1.2   Dermal Fibroblasts rest   13.9       Dendritic cells anti-CD40   3.8   Neutrophils TNFa + LPS   0.0       Monocytes rest   0.2   Neutrophils rest   1.7       Monocytes LPS   1.1   Colon   1.8       Macrophages rest   10.3   Lung   23.3       Macrophages LPS   3.4   Thymus   15.6       HUVEC none   49.7   Kidney   25.3       HUVEC starved   57.4                    
     [0767] CNS_neurodegeneration_v1.0 Summary: Ag4237 This panel confirms the expression of this gene at moderate levels in the brain in an independent group of individuals. This gene appears to be upregulated in the temporal cortex of Alzheimer&#39;s disease patients when compared with non-demented controls. Thus, based on the homology of this protein to Abeta protein binding family, therapeutic modulation of this gene or gene product may slow or stop the progression of Alzheimer&#39;s disease.  
     [0768] General_screening_panel_v1.4 Summary: Ag4237 Highest expression of this gene is seen in a breast cancer cell line (CT=27.2). High levels of expression are also seen in cell lines derived from brain, lung, and colon cancers, with moderate levels of expression in all the cancer cell lines on this panel. In addition, higher levels of expression are seen in fetal lung and liver (CTs=28.5-30.5) when compared to expression in the adult tissues (CTs=31.5-33.5). Thus, expression of this gene could be used to differentiate between the adult and fetal sources of these tissues. This expression profile also suggests a role for this gene product in cell survival and proliferation. Therefore, modulation of this gene product may be useful in the treatment of cancer.  
     [0769] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0770] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0771] Panel 4.1D Summary: Ag4237 Highest expression of this gene is seen in TNF-a and IL-1b treated HPAECs (CT=29.2). This gene is also expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     T. CG106988-01: Calreticulin  
     [0772] Expression of gene CG106988-01 was assessed using the primer-probe set Ag4333, described in Table TA. Results of the RTQ-PCR runs are shown in Table TB.  
               TABLE TA                          Probe Name Ag4333                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ataaaggtctgcaaaccactca-3′   22   260   147               Probe   TET-5′-attctatgccatctctgcacgcttca-3′-TAMRA   26   291   148               Reverse   5′-ccagagttttccctttattgct-3′   22   325   149                  
 
     [0773]               TABLE TB                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4333, Run       Ag4333, Run       Tissue Name   222556384   Tissue Name   222556384                                     Adipose   0.0   Renal ca. TK-10   0.1       Melanoma* Hs688(A).T   0.2   Bladder   0.0       Melanoma* Hs688(B).T   0.0   Gastric ca. (liver met.) NCI-   0.7               N87       Melanoma* M14   0.1   Gastric ca. KATO III   0.0       Melanoma* LOXIMVI   0.2   Colon ca. SW-948   0.1       Melanoma* SK-MEL-5   0.8   Colon ca. SW480   1.3       Squamous cell carcinoma   0.0   Colon ca.* (SW480 met)   0.3       SCC-4       SW620       Testis Pool   100.0   Colon ca. HT29   0.2       Prostate ca.* (bone met)   0.7   Colon ca. HCT-116   0.2       PC-3       Prostate Pool   0.0   Colon ca. CaCo-2   0.6       Placenta   0.2   Colon cancer tissue   0.1       Uterus Pool   0.0   Colon ca. SW1116   0.2       Ovarian ca. OVCAR-3   0.1   Colon ca. Colo-205   0.2       Ovarian ca. SK-OV-3   0.2   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   0.0   Colon Pool   0.0       Ovarian ca. OVCAR-5   0.1   Small Intestine Pool   0.2       Ovarian ca. IGROV-1   0.1   Stomach Pool   0.0       Ovarian ca. OVCAR-8   0.0   Bone Marrow Pool   0.0       Ovary   0.0   Fetal Heart   0.0       Breast ca. MCF-7   0.6   Heart Pool   0.0       Breast ca. MDA-MB-231   0.4   Lymph Node Pool   0.0       Breast ca. BT 549   0.1   Fetal Skeletal Muscle   0.1       Breast ca. T47D   0.7   Skeletal Muscle Pool   0.1       Breast ca. MDA-N   0.1   Spleen Pool   0.1       Breast Pool   0.0   Thymus Pool   0.0       Trachea   0.7   CNS cancer (glio/astro) U87-   0.3               MG       Lung   0.0   CNS cancer (glio/astro) U-   0.1               118-MG       Fetal Lung   0.0   CNS cancer (neuro;met) SK-   0.3               N-AS       Lung ca. NCI-N417   0.1   CNS cancer (astro) SF-539   0.1       Lung ca. LX-1   0.5   CNS cancer (astro) SNB-75   0.5       Lung ca. NCI-H146   0.1   CNS cancer (glio) SNB-19   0.3       Lung ca. SHP-77   1.4   CNS cancer (glio) SF-295   0.1       Lung ca. A549   0.5   Brain (Amygdala) Pool   0.0       Lung ca. NCI-H526   0.1   Brain (cerebellum)   0.2       Lung ca. NCI-H23   1.6   Brain (fetal)   0.1       Lung ca. NCI-H460   0.0   Brain (Hippocampus) Pool   0.2       Lung ca. HOP-62   0.0   Cerebral Cortex Pool   0.1       Lung ca. NCI-H522   1.6   Brain (Substantia nigra) Pool   0.0       Liver   0.0   Brain (Thalamus) Pool   0.0       Fetal Liver   0.3   Brain (whole)   0.1       Liver ca. HepG2   0.6   Spinal Cord Pool   0.0       Kidney Pool   0.1   Adrenal Gland   0.1       Fetal Kidney   0.2   Pituitary gland Pool   0.0       Renal ca. 786-0   0.4   Salivary Gland   0.0       Renal ca. A498   0.0   Thyroid (female)   0.0       Renal ca. ACHN   0.1   Pancreatic ca. CAPAN2   0.4       Renal ca. UO-31   0.0   Pancreas Pool   0.0                    
     [0774] General_screening_panel_v1.4 Summary: Ag4333 Highest expression of the CG106988-01 gene is detected in testis. Therefore, expression of this gene may be used to distinguish testis from other samples in this panel. In addition, therapeutic modulation of this gene may be beneficial in the treatement diseases that affect testis including fertility and hypogonadism.  
     [0775] In addition, low expression of this gene is also seen in two colon cancer cell lines, a prostate cancer cell line and a gastric cancer cell lines. Therefore, expression of this gene may be used as a marker to detect the presence of these cancers and therapeutic modulation of this gene product may be beneficial in the treatment of colon, gastric and prostate cancer.  
     U. CG107363-01: Protein Kinase C Inhibitor  
     [0776] Expression of gene CG107363-01, representing a full-length physical clone, was assessed using the primer-probe set Ag6926, described in Table UA. Results of the RTQ-PCR runs are shown in Table UB.  
               TABLE UA                          Probe Name Ag6926                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-agtgatattgcaacaatccgt-3′   21   440   150               Probe   TET-5′-ctcattcttgcctactttactctcccactg-3′-TAMRA   30   466   151               Reverse   5′-cataccaccttcaacgctaa-3′   20   503   152                  
 
     [0777]               TABLE UB                          General_screening_panel_v1.6                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag6926, Run       Ag6926, Run       Tissue Name   278700376   Tissue Name   278700376                                     Adipose   6.7   Renal ca. TK-10   24.0       Melanoma* Hs688(A).T   15.9   Bladder   16.4       Melanoma* Hs688(B).T   16.2   Gastric ca. (liver met.) NCI-   14.9               N87       Melanoma* M14   86.5   Gastric ca. KATO III   100.0       Melanoma* LOXIMVI   35.8   Colon ca. SW-948   20.6       Melanoma* SK-MEL-5   33.4   Colon ca. SW480   79.0       Squamous cell carcinoma   17.4   Colon ca.* (SW480 met)   59.9       SCC-4       SW620       Testis Pool   14.6   Colon ca. HT29   18.2       Prostate ca.* (bone met)   16.6   Colon ca. HCT-116   59.0       PC-3       Prostate Pool   4.2   Colon ca. CaCo-2   27.7       Placenta   3.6   Colon cancer tissue   14.7       Uterus Pool   3.8   Colon ca. SW1116   13.6       Ovarian ca. OVCAR-3   31.4   Colon ca. Colo-205   18.9       Ovarian ca. SK-OV-3   49.7   Colon ca. SW-48   8.2       Ovarian ca. OVCAR-4   20.4   Colon Pool   7.8       Ovarian ca. OVCAR-5   51.1   Small Intestine Pool   8.5       Ovarian ca. IGROV-1   26.1   Stomach Pool   5.1       Ovarian ca. OVCAR-8   38.2   Bone Marrow Pool   3.8       Ovary   6.0   Fetal Heart   8.4       Breast ca. MCF-7   55.9   Heart Pool   7.7       Breast ca. MDA-MB-231   81.8   Lymph Node Pool   10.6       Breast ca. BT 549   84.7   Fetal Skeletal Muscle   23.5       Breast ca. T47D   24.8   Skeletal Muscle Pool   6.3       Breast ca. MDA-N   35.6   Spleen Pool   7.5       Breast Pool   10.7   Thymus Pool   9.5       Trachea   6.4   CNS cancer (glio/astro) U87-   51.1               MG       Lung   5.6   CNS cancer (glio/astro) U-   63.7               118-MG       Fetal Lung   48.6   CNS cancer (neuro; met) SK-   31.0               N-AS       Lung ca. NCI-N417   23.2   CNS cancer (astro) SF-539   19.6       Lung ca. LX-1   22.5   CNS cancer (astro) SNB-75   54.0       Lung ca. NCI-H146   15.6   CNS cancer (glio) SNB-19   26.6       Lung ca. SHP-77   90.1   CNS cancer (glio) SF-295   55.5       Lung ca. A549   35.4   Brain (Amygdala) Pool   16.0       Lung ca. NCI-H526   10.2   Brain (cerebellum)   43.5       Lung ca. NCI-H23   22.2   Brain (fetal)   42.6       Lung ca. NCI-H460   27.4   Brain (Hippocampus) Pool   27.4       Lung ca. HOP-62   13.0   Cerebral Cortex Pool   24.1       Lung ca. NCI-H522   16.4   Brain (Substantia nigra) Pool   22.7       Liver   1.0   Brain (Thalamus) Pool   24.5       Fetal Liver   16.0   Brain (whole)   33.0       Liver ca. HepG2   7.1   Spinal Cord Pool   18.4       Kidney Pool   14.8   Adrenal Gland   19.9       Fetal Kidney   42.3   Pituitary gland Pool   7.4       Renal ca. 786-0   31.6   Salivary Gland   6.5       Renal ca. A498   14.8   Thyroid (female)   10.1       Renal ca. ACHN   14.8   Pancreatic ca. CAPAN2   22.1       Renal ca. UO-31   17.4   Pancreas Pool   9.4                    
     [0778] General_screening_panel_v1.6 Summary: Ag6926 Highest expression of this gene is seen in a gastric cancer cell line (CT=27.4). This gene is ubiquitously expressed in this panel, with high levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Therefore, modulation of this the expression or activity of this gene product may be useful in the treatment of cancer.  
     [0779] Among tissues with metabolic function, this gene is expressed at moderate levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0780] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0781] In addition, this gene is expressed at much higher levels in fetal liver tissue (CT=30) when compared to expression in the adult counterpart (CT=34). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.  
     V. CG107363-02 and CG107363-03: Protein Kinase C Inhibitor  
     [0782] Expression of gene CG107363-02 and variant CG107363-03 was assessed using the primer-probe set Ag4701, described in Table VA. Results of the RTQ-PCR runs are shown in Tables VB, VC and VD. Please note that these genes represent variants of the CG107363-01 gene described in the previous section (Section U) and that CG107363-03 is a full-length physical clone.  
               TABLE VA                          Probe Name Ag4701                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-cctgcatgtctgaagtccatag-3′   22   662   153               Probe   TET-5′tgtcagattatcacgtaacaactgcatga-3′-TAMRA   29   633   154               Reverse   5′-actggatacgctgagtgaagaa-3′   22   589   155                  
 
     [0783]               TABLE VB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4701, Run       Ag4701, Run       Tissue Name   224710831   Tissue Name   224710831                                     AD 1 Hippo   12.5   Control (Path) 3 Temporal   7.5               Ctx       AD 2 Hippo   36.9   Control (Path) 4 Temporal   33.9               Ctx       AD 3 Hippo   8.1   AD 1 Occipital Ctx   10.2       AD 4 Hippo   9.9   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   74.7   AD 3 Occipital Ctx   7.0       AD 6 Hippo   77.9   AD 4 Occipital Ctx   24.0       Control 2 Hippo   43.8   AD 5 Occipital Ctx   51.1       Control 4 Hippo   14.0   AD 6 Occipital Ctx   20.3       Control (Path) 3 Hippo   4.8   Control 1 Occipital Ctx   3.9       AD 1 Temporal Ctx   14.6   Control 2 Occipital Ctx   65.5       AD 2 Temporal Ctx   36.9   Control 3 Occipital Ctx   14.0       AD 3 Temporal Ctx   4.7   Control 4 Occipital Ctx   8.4       AD 4 Temporal Ctx   23.2   Control (Path) 1 Occipital   90.1               Ctx       AD 5 Inf Temporal Ctx   100.0   Control (Path) 2 Occipital   9.8               Ctx       AD 5 Sup Temporal Ctx   46.0   Control (Path) 3 Occipital   6.5               Ctx       AD 6 Inf Temporal Ctx   65.1   Control (Path) 4 Occipital   13.7               Ctx       AD 6 Sup Temporal Ctx   71.2   Control 1 Parietal Ctx   7.8       Control 1 Temporal Ctx   7.1   Control 2 Parietal Ctx   37.4       Control 2 Temporal Ctx   41.2   Control 3 Parietal Ctx   15.2       Control 3 Temporal Ctx   15.1   Control (Path) 1 Parietal Ctx   79.6       Control 3 Temporal Ctx   9.2   Control (Path) 2 Parietal Ctx   25.7       Control (Path) 1 Temporal   66.4   Control (Path) 3 Parietal Ctx   5.6       Ctx       Control (Path) 2 Temporal   36.1   Control (Path) 4 Parietal Ctx   45.1       Ctx                    
     [0784]               TABLE VC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4701, Run       Ag4701, Run       Tissue Name   222825540   Tissue Name   222825540                                     Adipose   10.4   Renal ca. TK-10   24.0       Melanoma* Hs688(A).T   22.1   Bladder   15.4       Melanoma* Hs688(B).T   19.3   Gastric ca. (liver met.) NCI-   18.6               N87       Melanoma* M14   70.7   Gastric ca. KATO III   87.7       Melanoma* LOXIMVI   39.2   Colon ca. SW-948   15.3       Melanoma* SK-MEL-5   36.9   Colon ca. SW480   97.3       Squamous cell carcinoma   20.0   Colon ca.* (SW480 met)   67.4       SCC-4       SW620       Testis Pool   11.9   Colon ca. HT29   25.7       Prostate ca.* (bone met)   29.5   Colon ca. HCT-116   65.5       PC-3       Prostate Pool   5.8   Colon ca. CaCo-2   47.0       Placenta   5.7   Colon cancer tissue   17.8       Uterus Pool   4.5   Colon ca. SW1116   9.6       Ovarian ca. OVCAR-3   29.1   Colon ca. Colo-205   12.8       Ovarian ca. SK-OV-3   28.1   Colon ca. SW-48   8.4       Ovarian ca. OVCAR-4   12.5   Colon Pool   10.6       Ovarian ca. OVCAR-5   34.6   Small Intestine Pool   9.0       Ovarian ca. IGROV-1   25.3   Stomach Pool   5.6       Ovarian ca. OVCAR-8   19.8   Bone Marrow Pool   4.8       Ovary   9.7   Fetal Heart   24.0       Breast ca. MCF-7   35.4   Heart Pool   8.0       Breast ca. MDA-MB-231   77.9   Lymph Node Pool   11.7       Breast ca. BT 549   100.0   Fetal Skeletal Muscle   16.7       Breast ca. T47D   66.9   Skeletal Muscle Pool   15.3       Breast ca. MDA-N   36.9   Spleen Pool   6.0       Breast Pool   10.7   Thymus Pool   8.3       Trachea   11.1   CNS cancer (glio/astro)   42.3               U87-MG       Lung   3.9   CNS cancer (glio/astro) U-   62.9               118-MG       Fetal Lung   34.9   CNS cancer (neuro;met) SK-   23.5               N-AS       Lung ca. NCI-N417   11.7   CNS cancer (astro) SF-539   21.3       Lung ca. LX-1   45.1   CNS cancer (astro) SNB-75   52.9       Lung ca. NCI-H146   18.4   CNS cancer (glio) SNB-19   24.0       Lung ca. SHP-77   62.0   CNS cancer (glio) SF-295   70.2       Lung ca. A549   51.4   Brain (Amygdala) Pool   17.0       Lung ca. NCI-H526   10.4   Brain (cerebellum)   51.1       Lung ca. NCI-H23   25.5   Brain (fetal)   37.9       Lung ca. NCI-H460   24.1   Brain (Hippocampus) Pool   18.6       Lung ca. HOP-62   20.3   Cerebral Cortex Pool   21.0       Lung ca. NCI-H522   23.2   Brain (Substantia nigra)   14.5               Pool       Liver   2.0   Brain (Thalamus) Pool   32.3       Fetal Liver   18.0   Brain (whole)   29.5       Liver ca. HepG2   10.7   Spinal Cord Pool   19.6       Kidney Pool   14.5   Adrenal Gland   15.5       Fetal Kidney   32.3   Pituitary gland Pool   6.4       Renal ca. 786-0   29.5   Salivary Gland   6.5       Renal ca. A498   14.5   Thyroid (female)   7.7       Renal ca. ACHN   17.2   Pancreatic ca. CAPAN2   19.8       Renal ca. UO-31   24.5   Pancreas Pool   12.9                    
     [0785]               TABLE VD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4701, Run       Ag4701, Run       Tissue Name   200924228   Tissue Name   200924228                                     Secondary Th1 act   63.7   HUVEC IL-1 beta   100.0       Secondary Th2 act   57.8   HUVEC IFN gamma   94.0       Secondary Tr1 act   60.3   HUVEC TNF alpha + IFN   56.3               gamma       Secondary Th1 rest   5.0   HUVEC TNF alpha + IL4   65.1       Secondary Th2 rest   7.5   HUVEC IL-11   49.7       Secondary Tr1 rest   7.9   Lung Microvascular EC   90.8               none       Primary Th1 act   57.4   Lung Microvascular EC   64.2               TNF alpha + IL-1 beta       Primary Th2 act   54.7   Microvascular Dermal EC   61.6               none       Primary Tr1 act   51.1   Microsvasular Dermal EC   51.1               TNF alpha + IL-1 beta       Primary Th1 rest   8.7   Bronchial epithelium   52.5               TNF alpha + IL1 beta       Primary Th2 rest   4.6   Small airway epithelium   29.7               none       Primary Tr1 rest   11.1   Small airway epithelium   60.7               TNF alpha + IL-1 beta       CD45RA CD4 lymphocyte   58.6   Coronery artery SMC rest   52.9       act       CD45RO CD4 lymphocyte   47.0   Coronery artery SMC   49.0       act       TNF alpha + IL-1 beta       CD8 lymphocyte act   43.5   Astrocytes rest   41.8       Secondary CD8 lymphocyte   46.0   Astrocytes TNF alpha + IL-   31.9       rest       1 beta       Secondary CD8 lymphocyte   18.9   KU-812 (Basophil) rest   48.3       act       CD4 lymphocyte none   3.5   KU-812 (Basophil)   90.8               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   11.7   CCD1106 (Keratinocytes)   84.7       CD95 CH11       none       LAK cells rest   33.7   CCD1106 (Keratinocytes)   69.7               TNF alpha + IL-1 beta       LAK cells IL-2   29.5   Liver cirrhosis   12.9       LAK cells IL-2 + IL-12   21.6   NCI-H292 none   49.7       LAK cells IL-2 + IFN   19.5   NCI-H292 IL-4   68.3       gamma       LAK cells IL-2 + IL-18   19.3   NCI-H292 IL-9   87.7       LAK cells PMA/ionomycin   37.1   NCI-H292 IL-13   67.4       NK Cells IL-2 rest   29.9   NCI-H292 IFN gamma   59.9       Two Way MLR 3 day   20.7   HPAEC none   55.1       Two Way MLR 5 day   29.1   HPAEC TNF alpha + IL-1   95.3               beta       Two Way MLR 7 day   21.5   Lung fibroblast none   64.2       PBMC rest   6.3   Lung fibroblast TNF alpha +   38.7               IL-1 beta       PBMC PWM   36.1   Lung fibroblast IL-4   57.4       PBMC PHA-L   33.7   Lung fibroblast IL-9   72.7       Ramos (B cell) none   31.6   Lung fibroblast IL-13   52.1       Ramos (B cell) ionomycin   41.8   Lung fibroblast IFN gamma   71.2       B lymphocytes PWM   43.2   Dermal fibroblast CCD1070   90.8               rest       B lymphocytes CD40L and   17.7   Dermal fibroblast CCD1070   85.3       IL-4       TNF alpha       EOL-1 dbcAMP   59.5   Dermal fibroblast CCD1070   55.5               IL-1 beta       EOL-1 dbcAMP   45.1   Dermal fibroblast IFN   46.7       PMA/ionomycin       gamma       Dendritic cells none   27.2   Dermal fibroblast IL-4   88.9       Dendritic cells LPS   31.9   Dermal Fibroblasts rest   55.1       Dendritic cells anti-CD40   28.1   Neutrophils TNFa + LPS   10.7       Monocytes rest   23.2   Neutrophils rest   12.3       Monocytes LPS   48.0   Colon   12.2       Macrophages rest   27.5   Lung   29.9       Macrophages LPS   18.9   Thymus   24.7       HUVEC none   62.4   Kidney   37.1       HUVEC starved   88.3                    
     [0786] CNS_neurodegeneration_v1.0 Summary: Ag4701 This panel confirms the expression of the CG107363-02 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer&#39;s diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.  
     [0787] General_screening_panel_v1.4 Summary: Ag4701 Highest expression of the CG107363-02 gene is detected in breast cancer BT 549 cell line (CT=23.7). High levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.  
     [0788] Among tissues with metabolic or endocrine function, this gene is expressed at high levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.  
     [0789] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer&#39;s disease, Parkinson&#39;s disease, epilepsy, multiple sclerosis, schizophrenia and depression.  
     [0790] Panel 4.1D Summary: Ag4701 Highest expression of the CG107363-02 gene is detected in IL-beta treated HUVEC cells (CT=25.4). This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     W. CG108360-01: PAX Transcription Activation Domain Interacting Protein PTIP  
     [0791] Expression of gene CG108360-01 was assessed using the primer-probe set Ag4355, described in Table WA. Results of the RTQ-PCR runs are shown in Tables WB, WC and WD.  
               TABLE WA                          Probe Name Ag4355                                             Start   SEQ ID       Primers   Sequences   Length   Positon   No                                         Forward   5′-gtgtctgcagagttgttgatga-3′   22   2518   156               Probe   TET-5′-cctcccaaactgaaacagaatgaagt-3′-TAMRA   26   2551   157               Reverse   5′-cttcaattctggctcttttgg-3′-   21   2597   158                  
 
     [0792]               TABLE WB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4355, Run       Ag4355, Run       Tissue Name   224371499   Tissue Name   224371499                                     AD 1 Hippo   0.0   Control (Path) 3 Temporal   0.0               Ctx       AD 2 Hippo   0.0   Control (Path) 4 Temporal   0.0               Ctx       AD 3 Hippo   0.0   AD 1 Occipital Ctx   0.0       AD 4 Hippo   0.0   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   0.0   AD 3 Occipital Ctx   0.0       AD 6 Hippo   0.0   AD 4 Occipital Ctx   0.0       Control 2 Hippo   0.0   AD 5 Occipital Ctx   0.0       Control 4 Hippo   55.9   AD 6 Occipital Ctx   0.0       Control (Path) 3 Hippo   58.2   Control 1 Occipital Ctx   0.0       AD 1 Temporal Ctx   0.0   Control 2 Occipital Ctx   0.0       AD 2 Temporal Ctx   0.0   Control 3 Occipital Ctx   0.0       AD 3 Temporal Ctx   0.0   Control 4 Occipital Ctx   0.0       AD 4 Temporal Ctx   0.0   Control (Path) 1 Occipital   0.0               Ctx       AD 5 Inf Temporal Ctx   0.0   Control (Path) 2 Occipital   0.0               Ctx       AD 5 Sup Temporal Ctx   40.9   Control (Path) 3 Occipital   0.0               Ctx       AD 6 Inf Temporal Ctx   0.0   Control (Path) 4 Occipital   0.0               Ctx       AD 6 Sup Temporal Ctx   100.0   Control 1 Parietal Ctx   0.0       Control 1 Temporal Ctx   0.0   Control 2 Parietal Ctx   0.0       Control 2 Temporal Ctx   0.0   Control 3 Parietal Ctx   0.0       Control 3 Temporal Ctx   0.0   Control (Path) 1 Parietal   0.0               Ctx       Control 3 Temporal Ctx   0.0   Control (Path) 2 Parietal   0.0               Ctx       Control (Path) 1 Temporal   0.0   Control (Path) 3 Parietal   0.0       Ctx       Ctx       Control (Path) 2 Temporal   0.0   Control (Path) 4 Parietal   0.0       Ctx       Ctx                    
     [0793]               TABLE WC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4355, Run       Ag4355, Run       Tissue Name   222543194   Tissue Name   222543194                                     Adipose   9.2   Renal ca. TK-10   30.8       Melanoma* Hs688(A).T   12.7   Bladder   15.6       Melanoma* Hs688(B).T   13.2   Gastric ca. (liver met.) NCI-   2.9               N87       Melanoma* M14   57.8   Gastric ca. KATO III   100.0       Melanoma* LOXIMVI   37.1   Colon ca. SW-948   10.5       Melanoma* SK-MEL-5   92.0   Colon ca. SW480   86.5       Squamous cell carcinoma   20.0   Colon ca.* (SW480 met)   70.2       SCC-4       SW620       Testis Pool   18.4   Colon ca. HT29   28.9       Prostate ca.* (bone met)   15.5   Colon ca. HCT-116   61.1       PC-3       Prostate Pool   9.6   Colon ca. CaCo-2   62.9       Placenta   8.3   Colon cancer tissue   36.3       Uterus Pool   5.3   Colon ca. SW1116   20.4       Ovarian ca. OVCAR-3   20.7   Colon ca. Colo-205   17.6       Ovarian ca. SK-OV-3   35.4   Colon ca. SW-48   15.1       Ovarian ca. OVCAR-4   9.6   Colon Pool   11.9       Ovarian ca. OVCAR-5   33.9   Small Intestine Pool   18.2       Ovarian ca. IGROV-1   19.1   Stomach Pool   8.0       Ovarian ca. OVCAR-8   9.9   Bone Marrow Pool   7.3       Ovary   7.0   Fetal Heart   18.0       Breast ca. MCF-7   31.0   Heart Pool   5.6       Breast ca. MDA-MB-231   61.1   Lymph Node Pool   18.0       Breast ca. BT 549   70.7   Fetal Skeletal Muscle   9.1       Breast ca. T47D   51.4   Skeletal Muscle Pool   9.7       Breast ca. MDA-N   24.0   Spleen Pool   8.9       Breast Pool   15.2   Thymus Pool   31.6       Trachea   7.4   CNS cancer (glio/astro)   65.5               U87-MG       Lung   3.5   CNS cancer (glio/astro) U-   68.8               118-MG       Fetal Lung   30.4   CNS cancer (neuro;met)   33.9               SK-N-AS       Lung ca. NCI-N417   20.9   CNS cancer (astro) SF-539   22.4       Lung ca. LX-1   38.2   CNS cancer (astro) SNB-75   70.2       Lung ca. NCI-H146   18.9   CNS cancer (glio) SNB-19   17.3       Lung ca. SHP-77   34.9   CNS cancer (glio) SF-295   73.2       Lung ca. A549   49.0   Brain (Amygdala) Pool   3.0       Lung ca. NCI-H526   35.8   Brain (cerebellum)   41.2       Lung ca. NCI-H23   80.7   Brain (fetal)   12.8       Lung ca. NCI-H460   20.2   Brain (Hippocampus) Pool   2.6       Lung ca. HOP-62   8.8   Cerebral Cortex Pool   5.7       Lung ca. NCI-H522   40.1   Brain (Substantia nigra)   5.0               Pool       Liver   0.7   Brain (Thalamus) Pool   8.2       Fetal Liver   29.9   Brain (whole)   12.0       Liver ca. HepG2   15.2   Spinal Cord Pool   4.3       Kidney Pool   21.6   Adrenal Gland   8.2       Fetal Kidney   26.4   Pituitary gland Pool   5.1       Renal ca. 786-0   27.4   Salivary Gland   5.1       Renal ca. A498   31.9   Thyroid (female)   4.0       Renal ca. ACHN   15.8   Pancreatic ca. CAPAN2   49.7       Renal ca. UO-31   31.2   Pancreas Pool   17.2                    
     [0794]               TABLE WD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4355, Run       Ag4355, Run       Tissue Name   186365411   Tissue Name   186365411                                     Secondary Th1 act   71.2   HUVEC IL-1beta   23.8       Secondary Th2 act   54.3   HUVEC IFN gamma   22.7       Secondary Tr1 act   48.0   HUVEC TNF alpha + IFN   8.2               gamma       Secondary Th1 rest   10.5   HUVEC TNF alpha + IL4   19.9       Secondary Th2 rest   12.0   HUVEC IL-11   13.7       Secondary Tr1 rest   10.7   Lung Microvascular EC   22.7               none       Primary Th1 act   39.2   Lung Microvascular EC   17.6               TNF aplha + IL-1beta       Primary Th2 act   50.7   Microvascular Dermal EC   13.6               none       Primary Tr1 act   41.5   Microsvasular Dermal EC   11.6               TNF aplha + IL-1beta       Primary Th1 rest   9.8   Bronchial epithelium   15.9               TNF aplha + IL1beta       Primary Th2 rest   9.0   Small airway epithelium   6.3               none       Primary Tr1 rest   23.2   Small airway epithelium   12.5               TNF aplha + IL-1beta       CD45RA CD4 lymphocyte   46.3   Coronery artery SMC rest   8.7       act       CD45RO CD4 lymphocyte   62.9   Coronery artery SMC   6.3       act       TNF aplha + IL-1beta       CD8 lymphocyte act   58.2   Astrocytes rest   7.9       Secondary CD8 lymphocyte   54.7   Astrocytes TNF aplha + IL-   4.7       rest       1beta       Secondary CD8 lymphocyte   26.2   KU-812 (Basophil) rest   49.3       act       CD4 lymphocyte none   10.6   KU-812 (Basophil)   44.4               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-   19.5   CCD1106 (Keratinocytes)   25.5       CD95 CH11       none       LAK cells rest   15.3   CCD1106 (Keratinocytes)   15.7               TNF aplha + IL-1beta       LAK cells IL-2   31.4   Liver cirrhosis   4.3       LAK cells IL-2 + IL-12   25.7   NCI-H292 none   17.7       LAK cells IL-2 + IFN   19.6   NCI-H292 IL-4   34.2       gamma       LAK cells IL-2 + IL-18   39.2   NCI-H292 IL-9   37.9       LAK cells PMA/ionomycin   12.2   NCI-H292 IL-13   36.3       NK Cells IL-2 rest   56.6   NCI-H292 IFN gamma   26.8       Two Way MLR 3 day   21.3   HPAEC none   11.3       Two Way MLR 5 day   46.3   HPAEC TNF alpha + IL-1   21.2               beta       Two Way MLR 7 day   27.5   Lung fibroblast none   19.2       PBMC rest   11.1   Lung fibroblast TNF alpha +   11.0               IL-1beta       PBMC PWM   34.4   Lung fibroblast IL-4   13.1       PBMC PHA-L   35.1   Lung fibroblast IL-9   33.7       Ramos (B cell) none   36.9   Lung fibroblast IL-13   20.9       Ramos (B cell) ionomycin   60.3   Lung fibroblast IFN gamma   22.4       B lymphocytes PWM   51.8   Dermal fibroblast CCD1070   24.5               rest       B lymphocytes CD40L and   32.8   Dermal fibroblast CCD1070   53.2       IL-4       TNF alpha       EOL-1 dbcAMP   100.0   Dermal fibroblast CCD1070   19.1               IL-1beta       EOL-1 dbcAMP   47.6   Dermal fibroblast IFN   15.8       PMA/ionomycin       gamma       Dendritic cells none   13.3   Dermal fibroblast IL-4   22.4       Dendritic cells LPS   6.9   Dermal Fibroblasts rest   12.8       Dendritic cells anti-CD40   10.8   Neutrophils TNFa + LPS   1.7       Monocytes rest   15.2   Neutrophils rest   6.7       Monocytes LPS   15.2   Colon   6.2       Macrophages rest   13.3   Lung   6.7       Macrophages LPS   4.7   Thymus   94.6       HUVEC none   13.2   Kidney   15.2       HUVEC starved   22.5                    
     [0795] General_screening_panel 13 v1.4 Summary: Ag4355 Highest expression of this gene is seen in a gastric cancer cell line (CT=27.8). This gene is ubiquitously expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancers. In addition, this gene is expressed at much higher levels in fetal lung and liver (CTs=29) when compared to expression in the adult counterpart (CTs=32-35). Thus, expression of this gene may be used to differentiate between the fetal and adult sources of these tissues. Higher levels of expression of this gene in fetal tissue and cancer cell lines suggest a role for this gene product in cell survival and proliferation. Therefore, modulation of the expression or activity of gene product may be useful in the treatment of cancer.  
     [0796] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0797] This gene is also expressed at moderate to low but significant levels in the CNS, including the thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0798] Panel 4.1D Summary: Ag4355 This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease, with highest expression in eosinophils (CT=29.2). These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel 13 v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     X. CG108762-01: MAP1 Light Chain 3 Related Protein-like protein  
     [0799] Expression of gene CG108762-01 was assessed using the primer-probe set Ag4371, described in Table XA. Results of the RTQ-PCR runs are shown in Tables XB, XC, XD, XE and XF.  
               TABLE XA                          Probe Name Ag4371                                             Start   SEQ ID       Primer   Sequences   Lengh   Position   No                                         Forward   5′-aattcatctccgagctgagg-3′   20   202   159               Probe   TET-5′-tcaacaatgtcattctgcccaccagt-3′-TAMRA   26   240   160               Reverse   5′-tggtgttcctggtagagctg-3′   20   278   161                  
 
     [0800]               TABLE XB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4371, Run       Ag4371, Run       Tissue Name   224377285   Tissue Name   224377285                                     AD 1 Hippo   32.3   Control (Path) 3 Temporal   10.4               Ctx       AD 2 Hippo   56.3   Control (Path) 4 Temporal   18.4               Ctx       AD 3 Hippo   14.1   AD 1 Occipital Ctx   14.5       AD 4 Hippo   10.5   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   44.4   AD 3 Occipital Ctx   11.5       AD 6 Hippo   69.7   AD 4 Occipital Ctx   25.3       Control 2 Hippo   52.9   AD 5 Occipital Ctx   29.3       Control 4 Hippo   24.7   AD 6 Occipital Ctx   12.7       Control (Path) 3 Hippo   11.9   Control 1 Occipital Ctx   7.5       AD 1 Temporal Ctx   18.4   Control 2 Occipital Ctx   81.8       AD 2 Temporal Ctx   46.0   Control 3 Occipital Ctx   15.0       AD 3 Temporal Ctx   10.1   Control 4 Occipital Ctx   14.6       AD 4 Temporal Ctx   13.3   Control (Path) 1 Occipital   55.5               Ctx       AD 5 Inf Temporal Ctx   85.9   Control (Path) 2 Occipital   13.3               Ctx       AD 5 Sup Temporal Ctx   44.4   Control (Path) 3 Occipital   8.6               Ctx       AD 6 Inf Temporal Ctx   49.7   Control (Path) 4 Occipital   10.2               Ctx       AD 6 Sup Temporal Ctx   63.7   Control 1 Parietal Ctx   20.3       Control 1 Temporal Ctx   13.8   Control 2 Parietal Ctx   44.8       Control 2 Temporal Ctx   51.1   Control 3 Parietal Ctx   16.8       Control 3 Temporal Ctx   16.7   Control (Path) 1 Parietal Ctx   100.0       Control 3 Temporal Ctx   11.9   Control (Path) 2 Parietal Ctx   22.1       Control (Path) 1 Temporal   57.8   Control (Path) 3 Parietal Ctx   7.8       Ctx       Control (Path) 2 Temporal   48.3   Control (Path) 4 Parietal Ctx   27.0       Ctx                    
     [0801]               TABLE XC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4371, Run       Ag4371, Run       Tissue Name   222544262   Tissue Name   222544262                                     Adipose   31.6   Renal ca. TK-10   31.4       Melanoma* Hs688(A).T   58.6   Bladder   55.9       Melanoma* Hs688(B).T   49.3   Gastric ca. (liver met.) NCI-   26.2               N87       Melanoma* M14   50.3   Gastric ca. KATO III   47.0       Melanoma* LOXIMVI   36.9   Colon ca. SW-948   22.5       Melanoma* SK-MEL-5   88.3   Colon ca. SW480   48.0       Squamous cell carcinoma   18.4   Colon ca.* (SW480 met)   64.6       SCC-4       SW620       Testis Pool   24.5   Colon ca. HT29   17.7       Prostate ca.* (bone met)   44.1   Colon ca. HCT-116   41.2       PC-3       Prostate Pool   19.1   Colon ca. CaCo-2   24.0       Placenta   34.4   Colon cancer tissue   23.5       Uterus Pool   4.7   Colon ca. SW1116   9.4       Ovarian ca. OVCAR-3   32.5   Colon ca. Colo-205   13.0       Ovarian ca. SK-OV-3   23.7   Colon ca. SW-48   18.0       Ovarian ca. OVCAR-4   27.4   Colon Pool   25.5       Ovarian ca. OVCAR-5   52.1   Small Intestine Pool   23.5       Ovarian ca. IGROV-1   41.8   Stomach Pool   11.7       Ovarian ca. OVCAR-8   27.7   Bone Marrow Pool   31.9       Ovary   29.5   Fetal Heart   31.4       Breast ca. MCF-7   55.9   Heart Pool   24.1       Breast ca. MDA-MB-231   62.4   Lymph Node Pool   25.3       Breast ca. BT 549   85.9   Fetal Skeletal Muscle   23.2       Breast ca. T47D   86.5   Skeletal Muscle Pool   21.3       Breast ca. MDA-N   36.3   Spleen Pool   18.3       Breast Pool   24.1   Thymus Pool   21.0       Trachea   33.2   CNS cancer (glio/astro) U87-   55.1               MG       Lung   11.7   CNS cancer (glio/astro) U-   100.0               118-MG       Fetal Lung   55.9   CNS cancer (neuro;met) SK-   37.1               N-AS       Lung ca. NCI-N417   11.9   CNS cancer (astro) SF-539   35.4       Lung ca. LX-1   41.8   CNS cancer (astro) SNB-75   78.5       Lung ca. NCI-H146   21.0   CNS cancer (glio) SNB-19   36.3       Lung ca. SHP-77   45.4   CNS cancer (glio) SF-295   60.3       Lung ca. A549   48.3   Brain (Amygdala) Pool   33.9       Lung ca. NCI-H526   17.6   Brain (cerebellum)   47.6       Lung ca. NCI-H23   55.9   Brain (fetal)   26.4       Lung ca. NCI-H460   26.4   Brain (Hippocampus) Pool   19.9       Lung ca. HOP-62   34.6   Cerebral Cortex Pool   32.1       Lung ca. NCI-H522   41.2   Brain (Substantia nigra) Pool   31.6       Liver   7.3   Brain (Thalamus) Pool   39.8       Fetal Liver   32.8   Brain (whole)   49.7       Liver ca. HepG2   25.2   Spinal Cord Pool   32.5       Kidney Pool   42.6   Adrenal Gland   59.5       Fetal Kidney   37.1   Pituitary gland Pool   14.9       Renal ca. 786-0   43.8   Salivary Gland   33.7       Renal ca. A498   32.8   Thyroid (female)   36.9       Renal ca. ACHN   45.1   Pancreatic ca. CAPAN2   20.6       Renal ca. UO-31   56.3   Pancreas Pool   37.1                    
     [0802]               TABLE XD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4371, Run       Ag4371, Run       Tissue Name   186473883   Tissue Name   186473883                                     Secondary Th1 act   27.9   HUVEC IL-1beta   35.8       Secondary Th2 act   40.3   HUVEC IFN gamma   65.1       Secondary Tr1 act   36.3   HUVEC TNF alpha + IFN   32.3               gamma       Secondary Th1 rest   32.5   HUVEC TNF alpha + IL4   30.4       Secondary Th2 rest   25.9   HUVEC IL-11   35.4       Secondary Tr1 rest   26.4   Lung Microvascular EC none   95.9       Primary Th1 act   21.6   Lung Microvascular EC   75.8               TNF aplha + IL-1beta       Primary Th2 act   41.5   Microvascular Dermal EC   42.3               none       Primary Tr1 act   31.4   Microsvasular Dermal EC   33.4               TNF aplha + IL-1beta       Primary Th1 rest   22.4   Bronchial epithelium   40.1               TNF aplha + IL1beta       Primary Th2 rest   15.7   Small airway epithelium none   25.9       Primary Tr1 rest   19.2   Small airway epithelium   44.4               TNF aplha + IL-1beta       CD45RA CD4 lymphocyte   31.0   Coronery artery SMC rest   54.0       act       CD45RO CD4 lymphocyte   28.1   Coronery artery SMC   64.2       act       TNF aplha + IL-1beta       CD8 lymphocyte act   36.6   Astrocytes rest   33.9       Secondary CD8 lymphocyte   26.6   Astrocytes TNF aplha + IL-   30.4       rest       1beta       Secondary CD8 lymphocyte   13.4   KU-812 (Basophil) rest   24.0       act       CD4 lymphocyte none   16.6   (KU-812 (Basophil)   37.1               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   31.6   CCD1106 (Keratinocytes)   24.7       CH11       none       LAK cells rest   66.4   CCD1106 (Keratinocytes)   15.8               TNF aplha + IL-1beta       LAK cells IL-2   28.9   Liver cirrhosis   15.8       LAK cells IL-2 + IL-12   18.7   NCI-H292 none   35.6       LAK cells IL-2 + IFN gamma   15.4   NCI-H292 IL-4   40.6       LAK cells IL-2 + IL-18   16.4   NCI-H292 IL-9   38.7       LAK cells PMA/ionomycin   50.7   NCI-H292 IL-13   34.4       NK Cells IL-2 rest   47.6   NCI-H292 IFN gamma   31.4       Two Way MLR 3 day   42.3   HPAEC none   32.5       Two Way MLR 5 day   31.2   HPAEC TNF alpha + IL-1   68.8               beta       Two Way MLR 7 day   18.9   Lung fibroblast none   67.8       PBMC rest   27.2   Lung fibroblast TNF alpha +   29.9               IL-1beta       PBMC PWM   20.4   Lung fibroblast IL-4   41.8       PBMC PHA-L   31.4   Lung fibroblast IL-9   77.9       Ramos (B cell) none   14.1   Lung fibroblast IL-13   63.3       Ramos (B cell) ionomycin   24.8   Lung fibroblast IFN gamma   71.2       B lymphocytes PWM   14.9   Dermal fibroblast CCD1070   39.8               rest       B lymphocytes CD40L and   35.8   Dermal fibroblast CCD1070   63.7       IL-4       TNF alpha       EOL-1 dbcAMP   50.0   Dermal fibroblast CCD1070   15.0               IL-1beta       EOL-1 dbcAMP   22.5   Dermal fibroblast IFN gamma   38.7       PMA/ionomycin       Dendritic cells none   67.4   Dermal fibroblast IL-4   84.7       Dendritic cells LPS   52.1   Dermal Fibroblasts rest   40.1       Dendritic cells anti-CD40   65.1   Neutrophils TNFa + LPS   43.8       Monocytes rest   100.0   Neutrophils rest   66.9       Monocytes LPS   70.2   Colon   15.1       Macrophages rest   52.1   Lung   32.5       Macrophages LPS   31.6   Thymus   41.2       HUVEC none   34.9   Kidney   47.6       HUVEC starved   57.0                    
     [0803]               TABLE XE                          Panel CNS_1                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4371, Run       Ag4371,       Tissue Name   190320680   Tissue Name   Run 190320680                                     BA4 Control   10.2   BA17 PSP   15.4       BA4 Control2   21.6   BA17 PSP2   9.0       BA4 Alzheimer&#39;s2   3.1   Sub Nigra Control   41.5       BA4 Parkinson&#39;s   38.2   Sub Nigra Control2   32.1       BA4 Parkinson&#39;s2   69.3   Sub Nigra Alzheimer&#39;s2   14.8       BA4 Huntingon&#39;s   23.2   Sub Nigra Parkinson&#39;s2   57.8       BA4 Huntington&#39;s2   4.5   Sub Nigra Huntington&#39;s   100.0       BA4 PSP   10.1   Sub Nigra Huntington&#39;s2   12.5       BA4 PSP2   12.4   Sub Nigra PSP2   9.0       BA4 Depression   14.1   Sub Nigra Depression   13.7       BA4 Depression2   8.4   Sub Nigra Depression2   0.2       BA7 Control   54.3   Glob Palladus Control   18.6       BA7 Control2   28.3   Glob Palladus Control2   9.9       BA7 Alzheimer&#39;s2   6.4   Glob Palladus Alzheimer&#39;s   13.9       BA7 Parkinson&#39;s   27.0   Glob Palladus Alzheimer&#39;s2   6.7       BA7 Parkinson&#39;s2   25.5   Glob Palladus Parkinson&#39;s   90.8       BA7 Huntington&#39;s   32.8   Glob Palladus Parkinson&#39;s2   14.2       BA7 Huntington&#39;s2   55.9   Glob Palladus PSP   9.1       BA7 PSP   12.9   Glob Palladus PSP2   7.4       BA7 PSP2   30.4   Glob Palladus Depression   6.0       BA7 Depression   6.0   Temp Pole Control   15.4       BA9 Control   15.6   Temp Pole Control2   37.4       BA9 Control2   28.9   Temp Pole Alzheimer&#39;s   6.5       BA9 Alzheimer&#39;s   4.2   Temp Pole Alzheimer&#39;s2   4.4       BA9 Alzheimer&#39;s2   13.8   Temp Pole Parkinson&#39;s   24.7       BA9 Parkinson&#39;s   18.7   Temp Pole Parkinson&#39;s2   23.7       BA9 Parkinson&#39;s2   33.7   Temp Pole Huntington&#39;s   32.1       BA9 Huntington&#39;s   53.6   Temp Pole PSP   2.8       BA9 Huntington&#39;s2   17.4   Temp Pole PSP2   2.5       BA9 PSP   13.1   Temp Pole Depression2   7.5       BA9 PSP2   3.6   Cing Gyr Control   40.6       BA9 Depression   10.7   Cing Gyr Control2   19.6       BA9 Depression2   3.1   Cing Gyr Alzheimer&#39;s   23.3       BA17 Control   32.5   Cing Gyr Alzheimer&#39;s2   10.2       BA17 Control2   24.5   Cing Gyr Parkinson&#39;s   26.6       BA17 Alzheimer&#39;s2   6.3   Cing Gyr Parkinson&#39;s2   47.3       BA17 Parkinson&#39;s   38.2   Cing Gyr Huntington&#39;s   80.7       BA17 Parkinson&#39;s2   36.9   Cing Gyr Huntington&#39;s2   25.2       BA17 Huntington&#39;s   38.7   Cing Gyr PSP   25.3       BA17 Huntington&#39;s2   15.5   Cing Gyr PSP2   8.0       BA17 Depression   15.9   Cing Gyr Depression   5.3       BA17 Depression2   16.4   Cing Gyr Depression2   12.2                    
     [0804]               TABLE XF                          Panel CNS_1.1                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4371, Run       Ag4371,       Tissue Name   190026607   Tissue Name   Run 190026607                                     Cing Gyr Depression2   16.3   BA17 PSP2   15.1       Cing Gyr Depression   12.9   BA17 PSP   30.6       Cing Gyr PSP2   8.8   BA17 Huntington&#39;s2   7.7       Cing Gyr PSP   30.6   BA17 Huntington&#39;s   24.0       Cing Gyr Huntington&#39;s2   25.3   BA17 Parkinson&#39;s2   35.8       Cing Gyr Huntington&#39;s   100.0   BA17 Parkinson&#39;s   36.3       Cing Gyr Parkinson&#39;s2   28.1   BA17 Alzheimer&#39;s2   3.9       Cing Gyr Parkinson&#39;s   51.4   BA17 Control2   37.9       Cing Gyr Alzheimer&#39;s2   9.2   BA17 Control   35.4       Cing Gyr Alzheimer&#39;s   48.6   BA9 Depression2   7.8       Cing Gyr Control2   31.2   BA9 Depression   8.4       Cing Gyr Control   69.3   BA9 PSP2   5.3       Temp Pole Depression2   6.6   BA9 PSP   19.2       Temp Pole PSP2   4.6   BA9 Huntington&#39;s2   21.6       Temp Pole PSP   5.3   BA9 Huntington&#39;s   73.7       Temp Pole Huntington&#39;s   34.9   BA9 Parkinson&#39;s2   56.3       Temp Pole Parkinson&#39;s2   22.8   BA9 Parkinson&#39;s   26.1       Temp Pole Parkinson&#39;s   21.9   BA9 Alzheimer&#39;s2   12.3       Temp Pole Alzheimer&#39;s2   6.5   BA9 Alzheimer&#39;s   5.6       Temp Pole Alzheimer&#39;s   5.2   BA9 Control2   63.3       Temp Pole Control2   52.9   BA9 Control   19.3       Temp Pole Control   19.3   BA7 Depression   7.7       Glob Palladus Depression   10.3   BA7 PSP2   34.4       Glob Palladus PSP2   7.4   BA7 PSP   42.9       Glob Palladus PSP   9.7   BA7 Huntington&#39;s2   21.0       Glob Palladus Parkinson&#39;s2   13.3   BA7 Huntington&#39;s   39.2       Glob Palladus Parkinson&#39;s   68.3   BA7 Parkinson&#39;s2   15.1       Glob Palladus Alzheimer&#39;s2   11.4   BA7 Parkinson&#39;s   16.7       Glob Palladus Alzheimer&#39;s   26.8   BA7 Alzheimer&#39;s2   5.4       Glob Palladus Control2   8.2   BA7 Control2   28.5       Glob Palladus Control   24.7   BA7 Control   25.9       Sub Nigra Depression2   13.7   BA4 Depression2   7.6       Sub Nigra Depression   15.7   BA4 Depression   16.0       Sub Nigra PSP2   10.4   BA4 PSP2   26.6       Sub Nigra Huntington&#39;s2   37.4   BA4 PSP   10.4       Sub Nigra Huntington&#39;s   62.4   BA4 Huntington&#39;s2   7.7       Sub Nigra Parkinson&#39;s2   52.9   BA4 Huntington&#39;s   30.8       Sub Nigra Alzheimer&#39;s2   23.2   BA4 Parkinson&#39;s2   59.5       Sub Nigra Control2   13.1   BA4 Parkinson&#39;s   62.9       Sub Nigra Control   56.6   BA4 Alzheimer&#39;s2   5.2       BA17 Depression2   17.7   BA4 Control2   48.3       BA17 Depression   14.0   BA4 Control   26.2                    
     [0805] CNS_neurodegeneration_v1.0 Summary: Ag4371 This panel does not show differential expression of this gene in Alzheimer&#39;s disease. However, this expression profile confirms the expression of this gene at high levels in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.  
     [0806] General_screening_panel 13 v1.4 Summary: Ag4371 Highest expression of this gene is seen in a brain cancer cell line (CT=25.3). This gene is widely expressed in this panel, with high levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.  
     [0807] Among tissues with metabolic function, this gene is expressed at high to moderate levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0808] This gene is also expressed at high levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. This novel protein has homology to human MAP1 Light Chain 3 Related Protein (GABA(A)-receptor-associated protein). Type-A receptors for the neurotransmitter GABA (gamma-aminobutyric acid) are ligand-gated chloride channels that mediate inhibitory neurotransmission. Each subunit of the pentameric receptor protein has ligand-binding sites in the amino-terminal extracellular domain and four membrane-spanning regions, one of which forms a wall of the ion channel. Each subunit also has a large intracellular loop that may be a target for protein kinases and be required for subcellular targeting and membrane clustering of the receptor, perhaps by anchoring the receptor to the cytoskeleton. Neurotransmitter receptors need to be positioned in high density in the cell membrane at sites postsynaptic to nerve terminals releasing that neurotransmitter. Other members of the superfamily of ligand-gated ion-channel receptors associate in postsynaptic-membrane clusters by binding to the proteins rapsyn or gephyrin. Wang et al. identified a new cellular protein, GABA(A)-receptor-associated protein (GABARAP), which can interact with the gamma2 subunit of GABA(A) receptors. GABARAP binds to GABA(A) receptors both in vitro and in vivo, and co-localizes with the punctate staining of GABA(A) receptors on cultured cortical neurons. Sequence analysis shows similarity between GABARAP and light chain-3 of microtubule-associated proteins 1A and 1B. Moreover, the N terminus of GABARAP is highly positively charged and features a putative tubulin-binding motif. The interactions among GABA(A) receptors, GABARAP and tubulin suggest a mechanism for the targeting and clustering of GABA(A) receptors. Because of the homology to the GABA(A)-receptor-associated protein and the high levels of expression in the brain, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0809] References:  
     [0810] Wang H, Bedford F K, Brandon N J, Moss S J, Olsen R W. GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton. Nature Jan. 7, 1999; 397(6714):69-72.  
     [0811] Panel 4.1D Summary: Ag4371 Highest expression of this gene is seen in resting monocytes (CT=27.7). This gene is also expressed at moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     [0812] Panel CNS — 1 Summary: Ag4371 This panel confirms the expression of this gene at high levels in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.  
     [0813] Panel CNS — 1.1 Summary: Ag4371 This panel confirms the expression of this gene at high levels in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.  
     Y. CG108829-01: Novel Intracelular Signaling Protein  
     [0814] Expression of gene CG108829-01 was assessed using the primer-probe set Ag4370, described in Table YA. Results of the RTQ-PCR runs are shown in Tables YB and YC.  
               TABLE YA                          Probe Name Ag4370                                             Start   SEQ ID       Primer   Sequences   Length   Position   No                                         Forward   5′-tggactccgaaagtggtatatg-3′   22   724   162               Probe   TET-5′-cctcgactccgtgctgatggact-3′-TAMRA   23   754   163               Reverse   5′-gcctgcatgtagagcaaatcta-3′   22   789   164                  
 
     [0815]               TABLE YB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4370, Run       Ag4370, Run       Tissue Name   224376589   Tissue Name   224376589                                     AD 1 Hippo   38.4   Control (Path) 3 Temporal   1.4               Ctx       AD 2 Hippo   57.4   Control (Path) 4 Temporal   4.4               Ctx       AD 3 Hippo   9.6   AD 1 Occipital Ctx   40.3       AD 4 Hippo   4.1   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   4.7   AD 3 Occipital Ctx   1.7       AD 6 Hippo   4.8   AD 4 Occipital Ctx   9.5       Control 2 Hippo   1.4   AD 5 Occipital Ctx   6.2       Control 4 Hippo   100.0   AD 6 Occipital Ctx   2.9       Control (Path) 3 Hippo   0.0   Control 1 Occipital Ctx   1.7       AD 1 Temporal Ctx   46.0   Control 2 Occipital Ctx   0.0       AD 2 Temporal Ctx   19.8   Control 3 Occipital Ctx   8.8       AD 3 Temporal Ctx   5.1   Control 4 Occipital Ctx   27.7       AD 4 Temporal Ctx   2.4   Control (Path) 1 Occipital   11.7               Ctx       AD 5 Inf Temporal Ctx   16.7   Control (Path) 2 Occipital   1.0               Ctx       AD 5 SupTemporal Ctx   2.2   Control (Path) 3 Occipital   0.0               Ctx       AD 6 Inf Temporal Ctx   18.4   Control (Path) 4 Occipital   8.0               Ctx       AD 6 Sup Temporal Ctx   16.4   Control 1 Parietal Ctx   1.7       Control 1 Temporal Ctx   0.0   Control 2 Parietal Ctx   4.2       Control 2 Temporal Ctx   0.0   Control 3 Parietal Ctx   4.6       Control 3 Temporal Ctx   6.1   Control (Path) 1 Parietal   16.2               Ctx       Control 4 Temporal Ctx   10.9   Control (Path) 2 Parietal   4.4               Ctx       Control (Path) 1 Temporal   10.2   Control (Path) 3 Parietal   0.0       Ctx       Ctx       Control (Path) 2 Temporal   3.1   Control (Path) 4 Parietal   3.7       Ctx       Ctx                    
     [0816]               TABLE YC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4370, Run       Ag4370, Run       Tissue Name   222544261   Tissue Name   222544261                                     Adipose   12.9   Renal ca. TK-10   0.0       Melanoma* Hs688(A).T   0.0   Bladder   5.1       Melanoma* Hs688(B).T   0.0   Gastric ca. (liver met.) NCI-   2.9               N87       Melanoma* M14   0.0   Gastric ca. KATO III   0.0       Melanoma* LOXIMVI   0.0   Colon ca. SW-948   0.0       Melanoma* SK-MEL-5   3.0   Colon ca. SW480   0.0       Squamous cell carcinoma   6.7   Colon ca.* (SW480 met)   0.0       SCC-4       SW620       Testis Pool   99.3   Colon ca. HT29   0.0       Prostate ca.* (bone met) PC-3   2.9   Colon ca. HCT-116   2.2       Prostate Pool   100.0   Colon ca. CaCo-2   0.0       Placenta   0.0   Colon cancer tissue   5.6       Uterus Pool   4.2   Colon ca. SW1116   0.0       Ovarian ca. OVCAR-3   0.0   Colon ca. Colo-205   0.0       Ovarian ca. SK-OV-3   3.8   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   0.0   Colon Pool   9.6       Ovarian ca. OVCAR-5   2.6   Small Intestine Pool   13.6       Ovarian ca. IGROV-1   0.0   Stomach Pool   9.9       Ovarian ca. OVCAR-8   0.0   Bone Marrow Pool   0.0       Ovary   7.2   Fetal Heart   2.1       Breast ca. MCF-7   0.0   Heart Pool   13.6       Breast ca. MDA-MB-231   0.0   Lymph Node Pool   0.0       Breast ca. BT 549   2.4   Fetal Skeletal Muscle   0.0       Breast ca. T47D   0.0   Skeletal Muscle Pool   17.9       Breast ca. MDA-N   0.0   Spleen Pool   11.6       Breast Pool   0.0   Thymus Pool   11.2       Trachea   71.7   CNS cancer (glio/astro)   0.0               U87-MG       Lung   2.1   CNS cancer (glio/astro) U-   0.0               118-MG       Fetal Lung   4.8   CNS cancer (neuro;met)   2.5               SK-N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro) SF-539   0.0       Lung ca. LX-1   0.0   CNS cancer (astro) SNB-75   7.4       Lung ca. NCI-H146   0.0   CNS cancer (glio) SNB-19   4.0       Lung ca. SHP-77   0.0   CNS cancer (glio) SF-295   0.0       Lung ca. A549   0.0   Brain (Amygdala) Pool   5.1       Lung ca. NCI-H526   0.0   Brain (cerebellum)   18.9       Lung ca. NCI-H23   43.2   Brain (fetal)   35.4       Lung ca. NCI-H460   0.0   Brain (Hippocampus) Pool   21.9       Lung ca. HOP-62   0.0   Cerebral Cortex Pool   12.3       Lung ca. NCI-H522   0.0   Brain (Substantia nigra)   31.6               Pool       Liver   0.0   Brain (Thalamus) Pool   34.9       Fetal Liver   0.0   Brain (whole)   12.9       Liver ca. HepG2   0.0   Spinal Cord Pool   65.1       Kidney Pool   39.5   Adrenal Gland   2.6       Fetal Kidney   94.0   Pituitary gland Pool   8.7       Renal ca. 786-0   0.0   Salivary Gland   6.9       Renal ca. A498   0.0   Thyroid (female)   5.5       Renal ca. ACHN   0.0   Pancreatic ca. CAPAN2   0.0       Renal ca. UO-31   0.0   Pancreas Pool   8.0                    
     [0817] CNS_neurodegeneration_v1.0 Summary: Ag4370 This panel confirms the presence of this gene in the brain. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0818] General_screening_panel_v1.4 Summary: Ag4370 Highest expression of this gene is seen in prostate (CT=31.2). Moderate levels of gene expression are also seen in trachea, fetal kidney, spinal cord, and testis. Low but significant levels of gene expression are seen in all regions of the CNS examined. Thus, expression of this gene could be used to differentiate between prostate and other samples on this panel and as a marker of prostate tissue.  
     Z. CG108861-01: Fish-like Protein  
     [0819] Expression of gene CG108861-01 was assessed using the primer-probe set Ag4381, described in Table ZA. Results of the RTQ-PCR runs are shown in Tables ZB, ZC and ZD.  
               TABLE ZA                          Probe Name Ag4381                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-catctcacagtgtgacgaagtc-3′   22   405   165               Probe   TET-5′-ctcgacccgaggatgtcaaccct-3′-TAMRA   23   443   166               Reverse   5′-gaactgccatagtcctcttttg-3′   22   467   167                  
 
     [0820]               TABLE ZB                          CNS_neurodegeneration_panel_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4381, Run       Ag4381, Run       Tissue Name   224502233   Tissue Name   224502233                                     AD 1 Hippo   29.9   Control (Path) 3 Temporal   18.4               Ctx       AD 2 Hippo   39.5   Control (Path) 4 Temporal   39.5               Ctx       AD 3 Hippo   12.2   AD 1 Occipital Ctx   26.1       AD 4 Hippo   18.2   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   49.0   AD 3 Occipital Ctx   10.5       AD 6 Hippo   68.8   AD 4 Occipital Ctx   20.3       Control 2 Hippo   43.8   AD 5 Occipital Ctx   40.3       Control 4 Hippo   21.0   AD 6 Occipital Ctx   36.1       Control (Path) 3 Hippo   19.9   Control 1 Occipital Ctx   13.7       AD 1 Temporal Ctx   29.7   Control 2 Occipital Ctx   38.4       AD 2 Temporal Ctx   39.5   Control 3 Occipital Ctx   18.0       AD 3 Temporal Ctx   9.0   Control 4 Occipital Ctx   27.0       AD 4 Temporal Ctx   39.0   Control (Path) 1 Occipital   100.0               Ctx       AD 5 Inf Temporal Ctx   66.9   Control (Path) 2 Occipital   28.1               Ctx       AD 5 Sup Temporal Ctx   37.9   Control (Path) 3 Occipital   27.9               Ctx       AD 6 Inf Temporal Ctx   70.2   Control (Path) 4 Occipital   31.9               Ctx       AD 6 Sup Temporal Ctx   60.7   Control 1 Parietal Ctx   20.3       Control 1 Temporal Ctx   13.0   Control 2 Parietal Ctx   44.8       Control 2 Temporal Ctx   41.8   Control 3 Parietal Ctx   20.0       Control 3 Temporal Ctx   15.6   Control (Path) 1 Parietal Ctx   58.2       Control 3 Temporal Ctx   22.1   Control (Path) 2 Parietal Ctx   43.5       Control (Path) 1 Temporal   44.1   Control (Path) 3 Parietal Ctx   26.2       Ctx       Control (Path) 2 Temporal   45.7   Control (Path) 4 Parietal Ctx   57.8       Ctx                    
     [0821]               TABLE ZC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4381, Run       Ag4381, Run       Tissue Name   222567264   Tissue Name   222567264                                     Adipose   4.2   Renal ca. TK-10   14.9       Melanoma* Hs688(A).T   19.1   Bladder   11.7       Melanoma* Hs688(B).T   24.8   Gastric ca. (liver met.) NCI-   6.0               N87       Melanoma* M14   0.0   Gastric ca. KATO III   4.8       Melanoma* LOXIMVI   12.2   Colon ca. SW-948   8.4       Melanoma* SK-MEL-5   0.4   Colon ca. SW480   4.7       Squamous cell carcinoma   32.8   Colon ca.* (SW480 met)   6.7       SCC-4       SW620       Testis Pool   2.2   Colon ca. HT29   15.0       Prostate ca.* (bone met) PC-3   7.0   Colon ca. HCT-116   1.8       Prostate Pool   7.7   Colon ca. CaCo-2   16.2       Placenta   19.9   Colon cancer tissue   16.4       Uterus Pool   2.3   Colon ca. SW1116   3.9       Ovarian ca. OVCAR-3   5.0   Colon ca. Colo-205   25.5       Ovarian ca. SK-OV-3   8.7   Colon ca. SW-48   21.8       Ovarian ca. OVCAR-4   0.1   Colon Pool   11.1       Ovarian ca. OVCAR-5   14.6   Small Intestine Pool   7.9       Ovarian ca. IGROV-1   27.4   Stomach Pool   6.2       Ovarian ca. OVCAR-8   4.7   Bone Marrow Pool   8.0       Ovary   7.5   Fetal Heart   15.3       Breast ca. MCF-7   0.1   Heart Pool   5.9       Breast ca. MDA-MB-231   37.6   Lymph Node Pool   16.6       Breast ca. BT 549   100.0   Fetal Skeletal Muscle   11.4       Breast ca. T47D   15.7   Skeletal Muscle Pool   7.4       Breast ca. MDA-N   0.0   Spleen Pool   8.4       Breast Pool   12.1   Thymus Pool   11.3       Trachea   18.6   CNS cancer (glio/astro)   23.7               U87-MG       Lung   2.8   CNS cancer (glio/astro) U-   18.8               118-MG       Fetal Lung   58.2   CNS cancer (neuro; met) SK-   13.8               N-AS       Lung ca. NCI-N417   3.4   CNS cancer (astro) SF-539   21.3       Lung ca. LX-1   24.7   CNS cancer (astro) SNB-75   91.4       Lung ca. NCI-H146   2.3   CNS cancer (glio) SNB-19   24.8       Lung ca. SHP-77   16.7   CNS cancer (glio) SF-295   18.7       Lung ca. A549   17.8   Brain (Amygdala) Pool   16.4       Lung ca. NCI-H526   8.8   Brain (cerebellum)   24.0       Lung ca. NCI-H23   3.9   Brain (fetal)   32.5       Lung ca. NCI-H460   1.0   (Brain Hippocampus) Pool   15.4       Lung ca. HOP-62   3.0   Cerebral Cortex Pool   13.8       Lung ca. NCI-H522   4.6   Brain (Substantia nigra)   15.8               Pool       Liver   0.5   Brain (Thalamus) Pool   21.0       Fetal Liver   7.4   Brain (whole)   14.2       Liver ca. HepG2   67.8   Spinal Cord Pool   15.9       Kidney Pool   14.9   Adrenal Gland   3.0       Fetal Kidney   5.9   Pituitary gland Pool   1.7       Renal ca. 786-0   0.9   Salivary Gland   4.7       Renal ca. A498   1.7   Thyroid (female)   0.9       Renal ca. ACHN   2.7   Pancreatic ca. CAPAN2   2.6       Renal ca. UO-31   0.6   Pancreas Pool   14.2                    
     [0822]               TABLE ZD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4381, Run       Ag4381, Run       Tissue Name   186504880   Tissue Name   186504880                                     Secondary Th1 act   0.9   HUVEC IL-1beta   6.5       Secondary Th2 act   0.8   HUVEC IFN gamma   4.4       Secondary Tr1 act   1.4   HUVEC TNF alpha + IFN   2.1               gamma       Secondary Th1 rest   2.3   HUVEC TNF alpha + IL4   4.9       Secondary Th2 rest   1.2   HUVEC IL-11   5.1       Secondary Tr1 rest   1.3   Lung Microvascular EC   16.4               none       Primary Th1 act   0.2   Lung Microvascular EC   24.0               TNF alpha + IL-1beta       Primary Th2 act   0.3   Microvascular Dermal EC   12.2               none       Primary Tr1 act   0.6   Microsvasular Dermal EC   24.1               TNF alpha + IL-1beta       Primary Th1 rest   0.5   Bronchial epithelium   46.3               TNF alpha + IL1beta       Primary Th2 rest   1.0   Small airway epithelium   32.3               none       Primary Tr1 rest   0.7   Small airway epithelium   49.3               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   2.7   Coronery artery SMC rest   2.8       act       CD45RO CD4 lymphocyte   0.8   Coronery artery SMC   5.8       act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   3.2       Secondary CD8 lymphocyte   0.9   Astrocytes TNF alpha + IL-   9.3       rest       1beta       Secondary CD8 lymphocyte   0.4   KU-812 (Basophil) rest   1.2       act       CD4 lymphocyte none   0.3   KU-812 (Basophil)   1.4               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   1.3   CCD1106 (Keratinocytes)   100.0       CH11       none       LAK cells rest   2.1   CCD1106 (Keratinocytes)   60.7               TNF alpha + IL-1beta       LAK cells IL-2   0.3   Liver cirrhosis   5.4       LAK cells IL-2 + IL-12   0.4   NCI-H292 none   17.1       LAK cells IL-2 + IFN gamma   0.7   NCI-H292 IL-4   21.5       LAK cells IL-2 + IL-18   0.9   NCI-H292 IL-9   21.2       LAK cells PMA/ionomycin   1.0   NCI-H292 IL-13   16.7       NK Cells IL-2 rest   0.7   NCI-H292 IFN gamma   10.7       Two Way MLR 3 day   0.5   HPAEC none   9.4       Two Way MLR 5 day   1.1   HPAEC TNF alpha + IL-   21.2               1beta       Two Way MLR 7 day   0.1   Lung fibroblast none   27.9       PBMC rest   0.3   Lung fibroblast TNF alpha +   11.0               IL-1beta       PBMC PWM   0.6   Lung fibroblast IL-4   32.3       PBMC PHA-L   1.6   Lung fibroblast IL-9   34.4       Ramos (B cell) none   0.0   Lung fibroblast IL-13   32.5       Ramos (B cell) ionomycin   0.0   Lung fibroblast IFN gamma   23.3       B lymphocytes PWM   0.1   Dermal fibroblast CCD1070   12.3               rest       B lymphocytes CD40L and   0.2   Dermal fibroblast CCD1070   10.7       IL-4       TNF alpha       EOL-1 dbcAMP   11.2   Dermal fibroblast CCD1070   4.7               IL-1beta       EOL-1 dbcAMP   36.1   Dermal fibroblast IFN   5.1       PMA/ionomycin       gamma       Dendritic cells none   13.1   Dermal fibroblast IL-4   17.7       Dendritic cells LPS   4.1   Dermal Fibroblasts rest   8.0       Dendritic cells anti-CD40   17.9   Neutrophils TNFa+LPS   0.4       Monocytes rest   0.0   Neutrophils rest   1.2       Monocytes LPS   0.1   Colon   2.9       Macrophages rest   3.2   Lung   11.3       Macrophages LPS   0.1   Thymus   6.4       HUVEC none   4.9   Kidney   2.6       HUVEC starved   2.7                    
     [0823] CNS_neurodegeneration_v1.0 Summary: Ag4381 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.  
     [0824] General_screening_panel 13 v1.4 Summary: Ag4381 Highest expression of this gene is seen in a breast cancer cell line (CT=25.5). High levels of gene expression are seen in cell lines derived from brain, colon, liver, lung, breast, ovarian, and skin cancers. In addition, this gene is expressed at much higher levels in fetal lung and liver (CTs=26-29) when compared to expression in the adult counterpart (CTs=30-33). Thus, expression of this gene may be used to differentiate between the fetal and adult sources of these tissues. The high levels of expression of this gene in fetal tissue and cancer cell lines suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.  
     [0825] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0826] This gene is also expressed at high to moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0827] Panel 4.1D Summary: Ag4381 Highest expression is seen in untreated keratinocytes (CT=26.7). This gene is also expressed at moderate to low levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel 13 v1.5 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     AA. CG109523-01: Profilaggrin  
     [0828] Expression of gene CG109523-01 was assessed using the primer-probe set Ag4388, described in Table AAA. Results of the RTQ-PCR runs are shown in Tables AAB and AAC.  
               TABLE AAA                          Probe Name Ag4388                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tgaaggaacttctggaaaagg-3′   21   102   168               Probe   TET-5′-ttcggcaaatcctgaagaatccagat-3′-TAMRA   26   126   169               Reverse   5′-tccaagtgatccatgaagaca-3′   21   169   170                  
 
     [0829]               TABLE AAB                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4388, Run       Ag4388, Run       Tissue Name   222567012   Tissue Name   222567012                                     Adipose   0.0   Renal ca. TK-10   0.1       Melanoma* Hs688(A).T   2.4   Bladder   0.0       Melanoma* Hs688(B).T   45.7   Gastric ca. (liver met.) NCI-   0.2               N87       Melanoma* M14   0.0   Gastric ca. KATO III   0.0       Melanoma* LOXIMVI   2.8   Colon ca. SW-948   0.0       Melanoma* SK-MEL-5   0.0   Colon ca. SW480   0.0       Squamous cell carcinoma   0.2   Colon ca.* (SW480 met)   0.1       SCC-4       SW620       Testis Pool   0.0   Colon ca. HT29   0.1       Prostate ca.* (bone met)   0.0   Colon ca. HCT-116   0.0       PC-3       Prostate Pool   0.0   Colon ca. CaCo-2   0.0       Placenta   0.0   Colon cancer tissue   0.0       Uterus Pool   0.1   Colon ca. SW1116   0.0       Ovarian ca. OVCAR-3   100.0   Colon ca. Colo-205   0.0       Ovarian ca. SK-OV-3   0.0   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   0.0   Colon Pool   0.0       Ovarian ca. OVCAR-5   0.0   Small Intestine Pool   0.0       Ovarian ca. IGROV-1   0.2   Stomach Pool   0.0       Ovarian ca. OVCAR-8   1.0   Bone Marrow Pool   0.1       Ovary   0.0   Fetal Heart   0.0       Breast ca. MCF-7   0.0   Heart Pool   0.0       Breast ca. MDA-MB-231   12.6   Lymph Node Pool   0.0       Breast ca. BT 549   0.0   Fetal Skeletal Muscle   0.0       Breast ca. T47D   0.0   Skeletal Muscle Pool   0.0       Breast ca. MDA-N   0.0   Spleen Pool   0.0       Breast Pool   0.0   Thymus Pool   0.2       Trachea   0.0   CNS cancer (glio/astro) U87-   0.0               MG       Lung   0.0   CNS cancer (glio/astro) U-118-   0.0               MG       Fetal Lung   0.1   CNS cancer (neuro; met) SK-   0.0               N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro) SF-539   0.0       Lung ca. LX-1   0.2   CNS cancer (astro) SNB-75   0.3       Lung ca. NCI-H146   0.0   CNS cancer (glio) SNB-19   0.3       Lung ca. SHP-77   0.0   CNS cancer (glio) SF-295   0.0       Lung ca. A549   0.0   Brain (Amygdala) Pool   0.0       Lung ca. NCI-H526   0.0   Brain (cerebellum)   0.0       Lung ca. NCI-H23   0.0   Brain (fetal)   0.0       Lung ca. NCI-H460   0.0   Brain (Hippocampus) Pool   0.0       Lung ca. HOP-62   0.0   Cerebral Cortex Pool   0.0       Lung ca. NCI-H522   0.0   Brain (Substantia nigra) Pool   0.0       Liver   0.0   Brain (Thalamus) Pool   0.0       Fetal Liver   0.0   Brain (whole)   0.0       Liver ca. HepG2   0.0   Spinal Cord Pool   0.0       Kidney Pool   0.0   Adrenal Gland   0.0       Fetal Kidney   0.2   Pituitary gland Pool   0.0       Renal ca. 786-0   51.4   Salivary Gland   0.0       Renal ca. A498   0.0   Thyroid (female)   0.0       Renal ca. ACHN   0.6   Pancreatic ca. CAPAN2   1.0       Renal ca. UO-31   0.0   Pancreas Pool   0.0                    
     [0830]               TABLE AAC                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4388, Run       Ag4388, Run       Tissue Name   186502000   Tissue Name   186502000                                     Secondary Th1 act   0.0   HUVEC IL-1beta   0.0       Secondary Th2 act   0.0   HUVEC IFN gamma   0.0       Secondary Tr1 act   0.0   HUVEC TNF alpha + IFN   0.0               gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha + IL4   0.0       Secondary Th2 rest   0.0   HUVEC IL-11   0.0       Secondary Tr1 rest   0.0   Lung Microvascular EC none   0.0       Primary Th1 act   0.0   Lung Microvascular EC   0.0               TNF alpha + IL-1beta       Primary Th2 act   0.0   Microvascular Dermal EC   0.0               none       Primary Tr1 act   0.0   Microsvasular Dermal EC   0.0               TNF alpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   0.0               TNF alpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium none   0.8       Primary Tr1 rest   0.0   Small airway epithelium   2.9               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   0.0   Coronery artery SMC rest   0.0       act       CD45RO CD4 lymphocyte   0.0   Coronery artery SMC   0.0       act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   100.0       Secondary CD8 lymphocyte   0.0   Astrocytes TNF alpha + IL-   27.9       rest       1beta       Secondary CD8 lymphocyte   0.0   KU-812 (Basophil) rest   0.0       act       CD4 lymphocyte none   0.0   KU-812 (Basophil)   0.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   0.0   CCD1106 (Keratinocytes)   0.6       CH11       none       LAK cells rest   0.0   CCD1106 (Keratinocytes)   0.8               TNF alpha + IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   0.0       LAK cells IL-2 + IL-12   0.0   NCI-H292 none   0.0       LAK cells IL-2 + IFN gamma   0.0   NCI-H292 IL-4   0.6       LAK cells IL-2 + IL-18   0.0   NCI-H292 IL-9   0.0       LAK cells PMA/ionomycin   0.0   NCI-H292 IL-13   0.4       NK Cells IL-2 rest   0.0   NCI-H292 IFN gamma   0.0       Two Way MLR 3 day   0.0   HPAEC none   0.0       Two Way MLR 5 day   0.0   HPAEC TNF alpha + IL-1   0.0               beta       Two Way MLR 7 day   0.0   Lung fibroblast none   0.0       PBMC rest   0.0   Lung fibroblast TNF alpha +   0.0               IL-1beta       PBMC PWM   0.0   Lung fibroblast IL-4   0.0       PBMC PHA-L   0.0   Lung fibroblast IL-9   0.0       Ramos (B cell) none   0.0   Lung fibroblast IL-13   0.0       Ramos (B cell) ionomycin   0.0   Lung fibroblast IFN gamma   0.0       B lymphocytes PWM   0.0   Dermal fibroblast CCD1070   0.0               rest       B lymphocytes CD40L and   0.0   Dermal fibroblast CCD1070   0.0       IL-4       TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast CCD1070   0.0               IL-1beta       EOL-1 dbcAMP   0.0   Dermal fibroblast IFN gamma   0.0       PMA/ionomycin       Dendritic cells none   0.0   Dermal fibroblast IL-4   0.0       Dendritic cells LPS   0.0   Dermal Fibroblasts rest   0.0       Dendritic cells anti-CD40   0.0   Neutrophils TNFa+LPS   0.0       Monocytes rest   0.0   Neutrophils rest   0.0       Monocytes LPS   0.0   Colon   0.0       Macrophages rest   0.0   Lung   0.0       Macrophages LPS   0.0   Thymus   2.5       HUVEC none   0.0   Kidney   0.5       HUVEC starved   0.0                    
     [0831] General_screening_panel 13 v1.4 Summary: Ag4388 Highest expression of the CG109523-01 gene is detected in ovarian cancer OVCAR-3 cell line (CT=26). Moderate to high levels of expression of this gene are also seen in number of cancer cell lines including pancreatic, renal, breast and melanoma cancer cell lines. Therefore, expression of this gene may be used as diagnostic marker for detection of these cancers and therapeutic modulation of this gene product may be beneficial in the treatment of these cancers  
     [0832] Panel 4.1D Summary: Ag4388 Highest expression of the CG109523-01 gene is detected in resting astrocytes (CT=29.4). Moderate expression of this gene is also seen in TNFalpha+IL-1beta stimulated astrocytes (CT=31.3). Therefore, therapeutic regulation of this gene or the design of therapeutics with the encoded protein could be important in the treatment of multiple sclerosis or other inflammatory diseases of the CNS. In addition, expression of this gene may also used to distinguish astrocytes from other samples used in this panel.  
     AB. CG109649-01: Novel Intracellular Signaling Protein  
     [0833] Expression of gene CG109649-01 was assessed using the primer-probe set Ag4394, described in Table ABA. Results of the RTQ-PCR runs are shown in Tables ABB, ABC and ABD.  
               TABLE ABA                          Probe Name Ag4394                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-actgggagctttgacaacaac-3′   21   367   171               Probe   TET-5′-ctattccgacttcgcgaagctccag-3′-TAMRA   25   408   172               Reverse   5′gatctcctccctgaacgtctt-3′   21   445   173                  
 
     [0834]               TABLE ABB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4394, Run       Ag4394, Run       Tissue Name   224502243   Tissue Name   224502243                                     AD 1 Hippo   19.9   Control (Path) 3 Temporal   6.9               Ctx       AD 2 Hippo   26.6   Control (Path) 4 Temporal   9.6               Ctx       AD 3 Hippo   7.8   AD 1 Occipital Ctx   20.2       AD 4 Hippo   4.4   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   66.0   AD 3 Occipital Ctx   4.5       AD 6 Hippo   100.0   AD 4 Occipital Ctx   18.9       Control 2 Hippo   14.4   AD 5 Occipital Ctx   26.8       Control 4 Hippo   29.1   AD 6 Occipital Ctx   18.2       Control (Path) 3 Hippo   3.5   Control 1 Occipital Ctx   13.4       AD 1 Temporal Ctx   38.4   Control 2 Occipital Ctx   30.4       AD 2 Temporal Ctx   17.2   Control 3 Occipital Ctx   1.7       AD 3 Temporal Ctx   8.8   Control 4 Occipital Ctx   4.3       AD 4 Temporal Ctx   20.6   Control (Path) 1 Occipital   31.4               Ctx       AD 5 Inf Temporal Ctx   72.2   Control (Path) 2 Occipital   7.5               Ctx       AD 5 Sup Temporal Ctx   60.7   Control (Path) 3 Occipital   1.8               Ctx       AD 6 Inf Temporal Ctx   81.8   Control (Path) 4 Occipital   39.5               Ctx       AD 6 Sup Temporal Ctx   64.2   Control 1 Parietal Ctx   4.5       Control 1 Temporal Ctx   12.6   Control 2 Parietal Ctx   38.2       Control 2 Temporal Ctx   57.8   Control 3 Parietal Ctx   11.0       Control 3 Temporal Ctx   21.6   Control (Path) 1 Parietal Ctx   15.1       Control 3 Temporal Ctx   3.6   Control (Path) 2 Parietal Ctx   9.2       Control (Path) 1 Temporal   27.5   Control (Path) 3 Parietal Ctx   0.0       Ctx       Control (Path) 2 Temporal   14.9   Control (Path) 4 Parietal Ctx   30.8       Ctx                    
     [0835]               TABLE ABC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4394, Run       Ag4394, Run       Tissue Name   222641542   Tissue Name   222641542                                     Adipose   12.4   Renal ca. TK-10   0.0       Melanoma* Hs688(A).T   0.0   Bladder   39.5       Melanoma* Hs688(B).T   0.0   Gastric ca. (liver met.) NCI-   2.0               N87       Melanoma* M14   0.0   Gastric ca. KATO III   0.3       Melanoma* LOXIMVI   0.0   Colon ca. SW-948   0.5       Melanoma* SK-MEL-5   0.0   Colon ca. SW480   3.6       Squamous cell carcinoma   0.0   Colon ca.* (SW480 met)   20.3       SCC-4       SW620       Testis Pool   3.7   Colon ca. HT29   0.0       Prostate ca.* (bone met)   0.0   Colon ca. HCT-116   0.0       PC-3       Prostate Pool   4.6   Colon ca. CaCo-2   0.0       Placenta   10.7   Colon cancer tissue   47.6       Uterus Pool   3.8   Colon ca. SW1116   1.7       Ovarian ca. OVCAR-3   0.0   Colon ca. Colo-205   0.7       Ovarian ca. SK-OV-3   0.5   Colon ca. SW-48   3.2       Ovarian ca. OVCAR-4   0.0   Colon Pool   27.2       Ovarian ca. OVCAR-5   0.6   Small Intestine Pool   6.3       Ovarian ca. IGROV-1   0.0   Stomach Pool   12.9       Ovarian ca. OVCAR-8   0.0   Bone Marrow Pool   28.3       Ovary   9.2   Fetal Heart   3.9       Breast ca. MCF-7   0.0   Heart Pool   4.4       Breast ca. MDA-MB-231   0.0   Lymph Node Pool   22.1       Breast ca. BT 549   0.0   Fetal Skeletal Muscle   4.6       Breast ca. T47D   0.8   Skeletal Muscle Pool   1.5       Breast ca. MDA-N   0.0   Spleen Pool   62.4       Breast Pool   23.5   Thymus Pool   100.0       Trachea   32.8   CNS cancer (glio/astro)   0.0               U87-MG       Lung   3.9   CNS cancer (glio/astro) U-   0.3               118-MG       Fetal Lung   50.7   CNS cancer (neuro; met) SK-   0.0               N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro) SF-539   0.0       Lung ca. LX-1   4.9   CNS cancer (astro) SNB-75   0.0       Lung ca. NCI-H146   0.0   CNS cancer (glio) SNB-19   0.0       Lung ca. SHP-77   2.4   CNS cancer (glio) SF-295   0.0       Lung ca. A549   0.0   Brain (Amygdala) Pool   3.5       Lung ca. NCI-H526   0.0   Brain (cerebellum)   20.0       Lung ca. NCI-H23   0.0   Brain (fetal)   1.6       Lung ca. NCI-H460   0.0   Brain (Hippocampus) Pool   5.8       Lung ca. HOP-62   0.0   Cerebral Cortex Pool   2.4       Lung ca. NCI-H522   0.0   Brain (Substantia nigra)   4.4               Pool       Liver   6.4   Brain (Thalamus) Pool   9.3       Fetal Liver   24.8   Brain (whole)   4.7       Liver ca. HepG2   1.1   Spinal Cord Pool   12.9       Kidney Pool   28.3   Adrenal Gland   9.9       Fetal Kidney   8.8   Pituitary gland Pool   2.0       Renal ca. 786-0   0.0   Salivary Gland   9.6       Renal ca. A498   0.0   Thyroid (female)   7.4       Renal ca. ACHN   0.5   Pancreatic ca. CAPAN2   0.0       Renal ca. UO-31   0.0   Pancreas Pool   21.9                    
     [0836]               TABLE ABD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4394, Run       Ag4394, Run       Tissue Name   187715315   Tissue Name   187715315                                     Secondary Th1 act   21.2   HUVEC IL-1beta   0.0       Secondary Th2 act   26.6   HUVEC IFN gamma   0.3       Secondary Tr1 act   21.3   HUVEC TNF alpha + IFN   0.0               gamma       Secondary Th1 rest   29.3   HUVEC TNF alpha + IL4   0.0       Secondary Th2 rest   64.6   HUVEC IL-11   0.0       Secondary Tr1 rest   39.2   Lung Microvascular EC   0.0               none       Primary Th1 act   9.9   Lung Microvascular EC   0.0               TNF alpha + IL-1beta       Primary Th2 act   23.2   Microvascular Dermal EC   0.1               none       Primary Tr1 act   27.4   Microsvasular Dermal EC   0.0               TNF alpha + IL-1beta       Primary Th1 rest   27.2   Bronchial epithelium   0.0               TNF alpha + IL1beta       Primary Th2 rest   16.0   Small airway epithelium   0.1               none       Primary Tr1 rest   66.9   Small airway epithelium   0.0               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   22.4   Coronery artery SMC rest   0.0       act       CD45RO CD4 lymphocyte   79.0   Coronery artery SMC   0.0       act       TNF alpha + IL-1beta       CD8 lymphocyte act   42.0   Astrocytes rest   0.0       Secondary CD8 lymphocyte   50.3   Astrocytes TNF alpha + IL-   0.0       rest       1beta       Secondary CD8 lymphocyte   18.3   KU-812 (Basophil) rest   8.0       act       CD4 lymphocyte none   21.5   (KU-812 (Basophil)   12.2               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   49.7   CCD1106 (Keratinocytes)   0.0       CH11       none       LAK cells rest   47.0   CCD1106 (Keratinocytes)   0.0               TNF alpha + IL-1beta       LAK cells IL-2   57.0   Liver cirrhosis   0.3       LAK cells IL-2 + IL-12   27.9   NCI-H292 none   0.0       LAK cells IL-2 + IFN gamma   49.3   NCI-H292 IL-4   0.0       LAK cells IL-2 + IL-18   50.7   NCI-H292 IL-9   0.0       LAK cells PMA/ionomycin   23.2   NCI-H292 IL-13   0.0       NK Cells IL-2 rest   100.0   NCI-H292 IFN gamma   0.0       Two Way MLR 3 day   43.8   HPAEC none   0.0       Two Way MLR 5 day   30.6   HPAEC TNF alpha + IL-   0.0               1beta       Two Way MLR 7 day   21.8   Lung fibroblast none   0.0       PBMC rest   21.6   Lung fibroblast TNF alpha +   0.0               IL-1beta       PBMC PWM   28.5   Lung fibroblast IL-4   0.0       PBMC PHA-L   57.4   Lung fibroblast IL-9   0.0       Ramos (B cell) none   0.3   Lung fibroblast IL-13   0.0       Ramos (B cell) ionomycin   0.3   Lung fibroblast IFN gamma   0.0       B lymphocytes PWM   31.4   Dermal fibroblast CCD1070   0.0               rest       B lymphocytes CD40L and   50.7   Dermal fibroblast CCD1070   42.6       IL-4       TNF alpha       EOL-1 dbcAMP   66.4   Dermal fibroblast CCD1070   0.2               IL-1beta       EOL-1 dbcAMP   18.8   Dermal fibroblast IFN   0.2       PMA/ionomycin       gamma       Dendritic cells none   40.1   Dermal fibroblast IL-4   0.3       Dendritic cells LPS   34.4   Dermal Fibroblasts rest   0.0       Dendritic cells anti-CD40   44.1   Neutrophils TNFa+LPS   22.8       Monocytes rest   49.7   Neutrophils rest   51.1       Monocytes LPS   49.0   Colon   1.4       Macrophages rest   34.4   Lung   4.1       Macrophages LPS   34.9   Thymus   42.3       HUVEC none   0.0   Kidney   0.3       HUVEC starved   0.0                    
     [0837] CNS_neurodegeneration_v1.0 Summary: Ag4394 This panel confirms the expression of the CG 109649-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer&#39;s diseased postmortem brains and those of non-demented controls in this experiment. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.  
     [0838] General_screening_panel_v1.4 Summary: Ag4394 Highest expression of the CG109649-01 gene is detected in thymus (CT=3 1). Moderate levels of expression of this gene are also seen in spleen (CT=31.7). Therefore, expression of this gene can be used to distinguish between these samples and other samples used in this panel. In addition, therapeutic modulation of this gene may be useful as anti-inflammatory therapeutics for the treatment of allergies, autoimmune diseases, and inflammatory diseases.  
     [0839] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, adrenal gland, thyroid, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.  
     [0840] This gene is expressed at much higher levels in fetal (CT=32) compared to adult lung (CT=35.7). This observation suggests that expression of this gene can be used to distinguish fetal from adult lung. In addition, the relative overexpression of this gene in fetal skeletal muscle suggests that the protein product may enhance lung growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of lung related diseases.  
     [0841] In addition, this gene is expressed at low levels in some regions of the central nervous system examined, including thalamus, cerebellum, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer&#39;s disease, Parkinson&#39;s disease, epilepsy, multiple sclerosis, schizophrenia and depression.  
     [0842] Low levels of expression of this gene are also seen in a colon cancer sample and also in a colon cancer cell line. Therefore, expression of this gene may be used as marker to detect colon cancer and also therapeutic modulation of this gene product may be beneficial in the treatment of colon cancer.  
     [0843] Panel 4.1D Summary: Ag4394 Highest expression of the CG109649-0l gene is detected in IL2 treated NK Cells (CT=29). This gene is expressed by T lymphocytes prepared under a number of conditions at moderate levels and is expressed at higher levels in treated and untreated dendritic cells, monocytes, and macrophages, basophils, TNF alpha activated dermal fibroblasts, neutrophils, thymus and lung. Dendritic cells and macrophages are powerful antigen-presenting cells (APC) whose function is pivotal in the initiation and maintenance of normal immune responses. Autoimmunity and inflammation may also be reduced by suppression of this function. Therefore, small molecule drugs that antagonzie the function of this gene product may reduce or eliminate the symptoms in patients with several types of autoimmune and inflammatory diseases, such as lupus erythematosus, Crohn&#39;s disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.  
     AC. CG110063-01 and CG110063-02: Vp3 Domain Containing Protein  
     [0844] Expression of gene CG110063-01 and variant CG110063-02 was assessed using the primer-probe set Ag4407, described in Table ACA. Results of the RTQ-PCR runs are shown in Tables ACB, ACC and ACD. Please note that CG110063-02 represents a full-length physcial clone, verifying the CG110063-01 gene prediction.  
               TABLE AGA                          Probe Name Ag4407                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-cctatacctttcacctgaacca-3′   22   577   174               Probe   TET-5′-ctccactacgagtattcactgcccgg-3′-TAMRA   26   625   175               Reverse   5′-gttgacctagcaaccatgagat-3′   22   651   176                  
 
     [0845]               TABLE ACB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4407, Run       Ag4407, Run       Tissue Name   224505298   Tissue Name   224505298                                     AD 1 Hippo   12.5   Control (Path) 3 Temporal   1.5               Ctx       AD 2 Hippo   25.7   Control (Path) 4 Temporal   28.3               Ctx       AD 3 Hippo   4.6   AD 1 Occipital Ctx   6.7       AD 4 Hippo   6.6   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   61.1   AD 3 Occipital Ctx   0.9       AD 6 Hippo   54.0   AD 4 Occipital Ctx   29.5       Control 2 Hippo   23.0   AD 5 Occipital Ctx   12.5       Control 4 Hippo   2.6   AD 6 Occipital Ctx   50.3       Control (Path) 3 Hippo   7.2   Control 1 Occipital Ctx   0.0       AD 1 Temporal Ctx   13.3   Control 2 Occipital Ctx   100.0       AD 2 Temporal Ctx   44.1   Control 3 Occipital Ctx   16.2       AD 3 Temporal Ctx   4.1   Control 4 Occipital Ctx   6.8       AD 4 Temporal Ctx   16.2   Control (Path) 1 Occipital   56.3               Ctx       AD 5 Inf Temporal Ctx   73.7   Control (Path) 2 Occipital   8.1               Ctx       AD 5 Sup Temporal Ctx   36.9   Control (Path) 3 Occipital   2.8               Ctx       AD 6 Inf Temporal Ctx   28.1   Control (Path) 4 Occipital   14.5               Ctx       AD 6 Sup Temporal Ctx   58.2   Control 1 Parietal Ctx   4.7       Control 1 Temporal Ctx   10.7   Control 2 Parietal Ctx   37.4       Control 2 Temporal Ctx   37.4   Control 3 Parietal Ctx   28.9       Control 3 Temporal Ctx   15.1   Control (Path) 1 Parietal   72.2               Ctx       Control 4 Temporal Ctx   14.7   Control (Path) 2 Parietal   20.3               Ctx       Control (Path) 1 Temporal   74.7   Control (Path) 3 Parietal   4.7       Ctx       Ctx       Control (Path) 2 Temporal   30.6   Control (Path) 4 Parietal   54.3       Ctx       Ctx                    
     [0846]               TABLE ACC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4407, Run       Ag4407, Run       Tissue Name   222643602   Tissue Name   222643602                                     Adipose   0.8   Renal ca. TK-10   15.9       Melanoma* Hs688(A).T   6.9   Bladder   6.5       Melanoma* Hs688(B).T   5.3   Gastric ca. (liver met.) NCI-   40.9               N87       Melanoma* M14   21.2   Gastric ca. KATO III   41.8       Melanoma* LOXIMVI   6.9   Colon ca. SW-948   6.2       Melanoma* SK-MEL-5   21.8   Colon ca. SW480   28.7       Squamous cell carcinoma   100.0   Colon ca.* (SW480 met)   22.4       SCC-4       SW620       Testis Pool   4.3   Colon ca. HT29   11.2       Prostate ca.* (bone met) PC-3   28.7   Colon ca. HCT-116   47.0       Prostate Pool   3.2   Colon ca. CaCo-2   28.9       Placenta   3.0   Colon cancer tissue   8.2       Uterus Pool   1.2   Colon ca. SW1116   3.8       Ovarian ca. OVCAR-3   27.4   Colon ca. Colo-205   14.3       Ovarian ca. SK-OV-3   15.7   Colon ca. SW-48   10.2       Ovarian ca. OVCAR-4   8.2   Colon Pool   2.7       Ovarian ca. OVCAR-5   27.7   Small Intestine Pool   3.2       Ovarian ca. IGROV-1   7.9   Stomach Pool   2.2       Ovarian ca. OVCAR-8   5.9   Bone Marrow Pool   3.4       Ovary   3.0   Fetal Heart   3.1       Breast ca. MCF-7   15.5   Heart Pool   2.3       Breast ca. MDA-MB-231   15.4   Lymph Node Pool   3.5       Breast ca. BT 549   21.6   Fetal Skeletal Muscle   1.8       Breast ca. T47D   32.5   Skeletal Muscle Pool   1.9       Breast ca. MDA-N   6.8   Spleen Pool   2.0       Breast Pool   3.7   Thymus Pool   4.5       Trachea   12.5   CNS cancer (glio/astro)   13.2               U87-MG       Lung   1.3   CNS cancer (glio/astro) U-   25.7               118-MG       Fetal Lung   4.9   CNS cancer (neuro; met)   41.2               SK-N-AS       Lung ca. NCI-N417   3.8   CNS cancer (astro) SF-539   8.0       Lung ca. LX-1   38.7   CNS cancer (astro) SNB-75   31.4       Lung ca. NCI-H146   7.6   CNS cancer (glio) SNB-19   6.6       Lung ca. SHP-77   23.7   CNS cancer (glio) SF-295   31.2       Lung ca. A549   12.5   Brain (Amygdala) Pool   5.8       Lung ca. NCI-H526   3.7   Brain (cerebellum)   25.2       Lung ca. NCI-H23   20.2   Brain (fetal)   3.8       Lung ca. NCI-H460   17.1   Brain (Hippocampus) Pool   4.1       Lung ca. HOP-62   10.7   Cerebral Cortex Pool   7.4       Lung ca. NCI-H522   21.5   Brain (Substantia nigra)   5.5               Pool       Liver   1.3   Brain (Thalamus) Pool   6.6       Fetal Liver   6.5   Brain (whole)   5.1       Liver ca. HepG2   0.1   Spinal Cord Pool   3.9       Kidney Pool   4.2   Adrenal Gland   5.6       Fetal Kidney   4.7   Pituitary gland Pool   2.5       Renal ca. 786-0   17.0   Salivary Gland   2.5       Renal ca. A498   3.9   Thyroid (female)   5.6       Renal ca. ACHN   13.0   Pancreatic ca. CAPAN2   15.9       Renal ca. UO-31   8.8   Pancreas Pool   3.7                    
     [0847]               TABLE ACD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4407, Run       Ag4407, Run       Tissue Name   187791587   Tissue Name   187791587                                     Secondary Th1 act   6.3   HUVEC IL-1beta   2.5       Secondary Th2 act   8.1   HUVEC IFN gamma   1.9       Secondary Tr1 act   7.9   HUVEC TNF alpha + IFN   0.9               gamma       Secondary Th1 rest   1.5   HUVEC TNF alpha + IL4   2.9       Secondary Th2 rest   3.3   HUVEC IL-11   2.1       Secondary Tr1 rest   1.5   Lung Microvascular EC   5.7               none       Primary Th1 act   2.8   Lung Microvascular EC   2.9               TNF alpha + IL-1beta       Primary Th2 act   4.1   Microvascular Dermal EC   2.9               none       Primary Tr1 act   4.3   Microsvasular Dermal EC   1.4               TNF alpha + IL-1beta       Primary Th1 rest   1.8   Bronchial epithelium   27.9               TNF alpha + IL1beta       Primary Th2 rest   1.4   Small airway epithelium   26.6               none       Primary Tr1 rest   3.7   Small airway epithelium   92.0               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   5.1   Coronery artery SMC rest   1.8       act       CD45RO CD4 lymphocyte   5.7   Coronery artery SMC   1.6       act       TNF alpha + IL-1beta       CD8 lymphocyte act   5.3   Astrocytes rest   1.1       Secondary CD8 lymphocyte   3.7   Astrocytes TNF alpha + IL-   1.5       rest       1beta       Secondary CD8 lymphocyte   3.2   KU-812 (Basophil) rest   4.4       act       CD4 lymphocyte none   1.3   KU-812 (Basophil)   10.4               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   2.7   CCD1106 (Keratinocytes)   16.5       CH11       none       LAK cells rest   2.0   CCD1106 (Keratinocytes)   40.9               TNF alpha + IL-1beta       LAK cells IL-2   4.8   Liver cirrhosis   0.6       LAK cells IL-2 + IL-12   2.8   NCI-H292 none   51.1       LAK cells IL-2 + IFN gamma   2.4   NCI-H292 IL-4   91.4       LAK cells IL-2 + IL-18   1.4   NCI-H292 IL-9   66.4       LAK cells PMA/ionomycin   1.0   NCI-H292 IL-13   100.0       NK Cells IL-2 rest   4.9   NCI-H292 IFN gamma   55.9       Two Way MLR 3 day   4.8   HPAEC none   1.4       Two Way MLR 5 day   3.2   HPAEC TNF alpha + IL-1   2.3               beta       Two Way MLR 7 day   3.3   Lung fibroblast none   1.9       PBMC rest   0.1   Lung fibroblast TNF    1.9               alpha + IL-1beta       PBMC PWM   3.8   Lung fibroblast IL-4   2.2       PBMC PHA-L   5.4   Lung fibroblast IL-9   5.9       Ramos (B cell) none   6.6   Lung fibroblast IL-13   2.6       Ramos (B cell) ionomycin   9.2   Lung fibroblast IFN gamma   2.7       B lymphocytes PWM   3.2   Dermal fibroblast CCD1070   4.0               rest       B lymphocytes CD40L and   4.1   Dermal fibroblast CCD1070   6.1       IL-4       TNF alpha       EOL-1 dbcAMP   5.7   Dermal fibroblast CCD1070   3.5               IL-1beta       EOL-1 dbcAMP   3.1   Dermal fibroblast IFN   0.8       PMA/ionomycin       gamma       Dendritic cells none   1.9   Dermal fibroblast IL-4   1.6       Dendritic cells LPS   1.6   Dermal Fibroblasts rest   1.3       Dendritic cells anti-CD40   2.0   Neutrophils TNF a + LPS   1.7       Monocytes rest   0.5   Neutrophils rest   1.6       Monocytes LPS   1.8   Colon   0.9       Macrophages rest   2.3   Lung   1.1       Macrophages LPS   0.8   Thymus   1.7       HUVEC none   1.5   Kidney   3.2       HUVEC starved   3.6                    
     [0848] CNS_neurodegeneration_v1.0 Summary: Ag4407 This panel does not show differential expression of this gene in Alzheimer&#39;s disease. However, this expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.  
     [0849] General_screening_panel 13 v1.4 Summary: Ag4407 Highest expression of this gene is seen in a skin cancer cell line (CT=26.4). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancers. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.  
     [0850] Among tissues with metabolic function, this gene is expressed at moderate to low but significant levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0851] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0852] Panel 4.1D Summary: Ag4407 This transcript is widely expressed in this panel, with highest expression in NCI-H292 cells stimulated by IL-13 (CT=27.4). The gene is also expressed in a cluster of treated and untreated samples derived from the NCI-H292 cell line, a human airway epithelial cell line that produces mucins. Mucus overproduction is an important feature of bronchial asthma and chronic obstructive pulmonary disease samples. The transcript is also expressed in small airway epithelium treated with IL-1 beta and TNF-alpha, and at moderate levels in activated bronchial epithelium and untreated small airway epithelium. The expression of the transcript in this mucoepidermoid cell line that is often used as a model for airway epithelium (NCI-H292 cells) suggests that this transcript may be important in the proliferation or activation of airway epithelium. Therefore, therapeutics designed with the protein encoded by the transcript may reduce or eliminate symptoms caused by inflammation in lung epithelia in chronic obstructive pulmonary disease, asthma, allergy, and emphysema.  
     AD. CG110151-01: PX19 Like Protein  
     [0853] Expression of gene CG110151-01 was assessed using the primer-probe set Ag4404, described in Table ADA. Results of the RTQ-PCR runs are shown in Tables ADB and ADC.  
               TABLE ADA                          Probe Name Ag4404                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′tgtttcctgccaatgttgat-3′   20   224   177               Probe   TET-5′-cctggaggactctattgtggacccac-3′-TAMRA   26   258   178               Reverse   5′-gtgaaggtggtcatggtctg-3′   20   289   179                  
 
     [0854]               TABLE ADB                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4404, Run       Ag4404, Run       Tissue Name   222643401   Tissue Name   222643401                                     Adipose   0.0   Renal ca. TK-10   2.0       Melanoma* Hs688(A).T   0.9   Bladder   0.4       Melanoma* Hs688(B).T   0.2   Gastric ca. (liver met.) NCI-   1.0               N87       Melanoma* M14   3.7   Gastric ca. KATO III   9.1       Melanoma* LOXIMVI   3.2   Colon ca. SW-948   1.0       Melanoma* SK-MEL-5   3.2   Colon ca. SW480   4.5       Squamous cell carcinoma   1.9   Colon ca.* (SW480 met)   2.7       SCC-4       SW620       Testis Pool   1.6   Colon ca. HT29   1.8       Prostate ca.* (bone met)   4.2   Colon ca. HCT-116   3.6       PC-3       Prostate Pool   1.0   Colon ca. CaCo-2   5.2       Placenta   0.6   Colon cancer tissue   0.0       Uterus Pool   0.0   Colon ca. SW1116   0.5       Ovarian ca. OVCAR-3   1.5   Colon ca. Colo-205   0.8       Ovarian ca. SK-OV-3   1.4   Colon ca. SW-48   0.9       Ovarian ca. OVCAR-4   3.9   Colon Pool   1.3       Ovarian ca. OVCAR-5   4.8   Small Intestine Pool   0.5       Ovarian ca. IGROV-1   1.0   Stomach Pool   1.0       Ovarian ca. OVCAR-8   1.4   Bone Marrow Pool   0.0       Ovary   0.2   Fetal Heart   0.0       Breast ca. MCF-7   2.0   Heart Pool   1.6       Breast ca. MDA-MB-231   2.2   Lymph Node Pool   1.2       Breast ca. BT 549   5.3   Fetal Skeletal Muscle   0.1       Breast ca. T47D   100.0   Skeletal Muscle Pool   2.0       Breast ca. MDA-N   0.9   Spleen Pool   0.0       Breast Pool   0.8   Thymus Pool   0.0       Trachea   14.0   CNS cancer (glio/astro) U87-   1.8               MG       Lung   1.7   CNS cancer (glio/astro) U-118-   2.2               MG       Fetal Lung   0.0   CNS cancer (neuro; met) SK-   2.8               N-AS       Lung ca. NCI-N417   0.4   CNS cancer (astro) SF-539   0.4       Lung ca. LX-1   3.9   CNS cancer (astro) SNB-75   4.5       Lung ca. NCI-H146   0.5   CNS cancer (glio) SNB-19   0.8       Lung ca. SHP-77   2.5   CNS cancer (glio) SF-295   1.3       Lung ca. A549   2.4   Brain (Amygdala) Pool   0.7       Lung ca. NCI-H526   0.0   Brain (cerebellum)   1.0       Lung ca. NCI-H23   2.2   Brain (fetal)   0.9       Lung ca. NCI-H460   1.2   Brain (Hippocampus) Pool   0.8       Lung ca. HOP-62   2.5   Cerebral Cortex Pool   0.0       Lung ca. NCI-H522   2.0   Brain (Substantia nigra) Pool   1.0       Liver   0.8   Brain (Thalamus) Pool   1.0       Fetal Liver   0.1   Brain (whole)   0.4       Liver ca. HepG2   4.7   Spinal Cord Pool   1.9       Kidney Pool   0.1   Adrenal Gland   1.1       Fetal Kidney   1.5   Pituitary gland Pool   0.0       Renal ca. 786-0   2.1   Salivary Gland   0.2       Renal ca. A498   3.5   Thyroid (female)   0.2       Renal ca. ACHN   1.2   Pancreatic ca. CAPAN2   1.5       Renal ca. UO-31   0.4   Pancreas Pool   1.6                    
     [0855]               TABLE ADC                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4404, Run       Ag4404, Run       Tissue Name   190279047   Tissue Name   190279047                                     Secondary Th1 act   0.9   HUVEC IL-1beta   0.8       Secondary Th2 act   1.1   HUVEC IFN gamma   0.4       Secondary Tr1 act   3.1   HUVEC TNF alpha + IFN   0.8               gamma       Secondary Th1 rest   0.1   HUVEC TNF alpha + IL4   1.9       Secondary Th2 rest   0.6   HUVEC IL-11   0.9       Secondary Tr1 rest   0.2   Lung Microvascular EC none   1.3       Primary Th1 act   0.3   Lung Microvascular EC   3.1               TNF alpha + IL-1beta       Primary Th2 act   0.2   Microvascular Dermal EC   0.9               none       Primary Tr1 act   2.0   Microsvasular Dermal EC   2.5               TNF alpha + IL-1beta       Primary Th1 rest   0.5   Bronchial epithelium   1.2               TNF alpha + IL1beta       Primary Th2 rest   0.6   Small airway epithelium none   0.7       Primary Tr1 rest   0.1   Small airway epithelium   1.0               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   0.1   Coronery artery SMC rest   0.5       act       CD45RO CD4 lymphocyte   0.1   Coronery artery SMC   0.5       act       TNF alpha + IL-1beta       CD8 lymphocyte act   0.4   Astrocytes rest   1.2       Secondary CD8 lymphocyte   2.0   Astrocytes TNF alpha + IL-   0.3       rest       1beta       Secondary CD8 lymphocyte   0.4   KU-812 (Basophil) rest   2.6       act       CD4 lymphocyte none   0.2   KU-812 (Basophil)   1.5               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   0.2   CCD1106 (Keratinocytes)   2.2       CH11       none       LAK cells rest   0.4   CCD1106 (Keratinocytes)   3.7               TNF alpha + IL-1beta       LAK cells IL-2   0.5   Liver cirrhosis   0.1       LAK cells IL-2 + IL-12   0.8   NCI-H292 none   0.3       LAK cells IL-2 + IFN gamma   0.2   NCI-H292 IL-4   1.2       LAK cells IL-2 + IL-18   0.3   NCI-H292 IL-9   1.4       LAK cells PMA/ionomycin   0.0   NCI-H292 IL-13   0.2       NK Cells IL-2 rest   1.3   NCI-H292 IFN gamma   1.8       Two Way MLR 3 day   2.2   HPAEC none   0.7       Two Way MLR 5 day   2.8   HPAEC TNF alpha + IL-1   0.0               beta       Two Way MLR 7 day   0.7   Lung fibroblast none   0.0       PBMC rest   0.2   Lung fibroblast TNF alpha +   0.0               IL-1beta       PBMC PWM   1.0   Lung fibroblast IL-4   0.4       PBMC PHA-L   2.5   Lung fibroblast IL-9   2.1       Ramos (B cell) none   0.7   Lung fibroblast IL-13   0.4       Ramos (B cell) ionomycin   3.4   Lung fibroblast IFN gamma   0.7       B lymphocytes PWM   1.7   Dermal fibroblast CCD1070   0.4               rest       B lymphocytes CD40L and   0.4   Dermal fibroblast CCD1070   0.6       IL-4       TNF alpha       EOL-1 dbcAMP   1.9   Dermal fibroblast CCD1070   0.0               IL-1beta       EOL-1 dbcAMP   0.8   Dermal fibroblast IFN gamma   0.3       PMA/ionomycin       Dendritic cells none   0.7   Dermal fibroblast IL-4   1.3       Dendritic cells LPS   1.7   Dermal Fibroblasts rest   0.2       Dendritic cells anti-CD40   1.3   Neutrophils TNF a + LPS   0.4       Monocytes rest   2.2   Neutrophils rest   2.5       Monocytes LPS   1.3   Colon   0.0       Macrophages rest   0.9   Lung   2.2       Macrophages LPS   1.0   Thymus   15.0       HUVEC none   1.6   Kidney   100.0       HUVEC starved   1.5                    
     [0856] General_screening_panel 13 v1.4 Summary: Ag4404 Highest expression of this gene is seen in a breast cancer cell line (CT=29.2).). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of breast cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of breast cancer.  
     [0857] Panel 4.1D Summary: Ag4404 Highest expression of this gene is seen in kidney (CT=28.5). Thus, expression of this gene could be used to differentiate the kidney derived sample from other samples on this panel and as a marker of kidney tissue. In addition, therapeutic targeting of the expression or function of this gene may modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.  
     AE. CG110340-01: Polyubiquitin-like Protein  
     [0858] Expression of gene CG110340-01 was assessed using the primer-probe set Ag4445, described in Table AEA. Results of the RTQ-PCR runs are shown in Tables AEB, AEC and AED.  
               TABLE AEA                          Probe Name Ag4445                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tgcagatcttcgtgaagacc-3′   20   8   180               Probe   TET-5′-actggcaagaccatcacccttgaagt-3′-TAMRA   26   31   181               Reverse   5′-ccttcacattttcgatggtg-3′   20   69   182                  
 
     [0859]               TABLE AEB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4445, Run       Ag4445, Run       Tissue Name   224535012   Tissue Name   224535012                                     AD 1 Hippo   16.7   Control (Path) 3 Temporal   2.4               Ctx       AD 2 Hippo   31.9   Control (Path) 4 Temporal   34.4               Ctx       AD 3 Hippo   5.9   AD 1 Occipital Ctx   18.0       AD 4 Hippo   8.8   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 hippo   100.0   AD 3 Occipital Ctx   6.3       AD 6 Hippo   42.9   AD 4 Occipital Ctx   19.8       Control 2 Hippo   40.6   AD 5 Occipital Ctx   19.2       Control 4 Hippo   0.0   AD 6 Occipital Ctx   40.1       Control (Path) 3 Hippo   4.1   Control 1 Occipital Ctx   1.5       AD 1 Temporal Ctx   12.9   Control 2 Occipital Ctx   54.7       AD 2 Temporal Ctx   27.0   Control 3 Occipital Ctx   17.4       AD 3 Temporal Ctx   6.0   Control 4 Occipital Ctx   2.6       AD 4 Temporal Ctx   25.0   Control (Path) 1 Occipital   80.1               Ctx       AD 5 Inf Temporal Ctx   87.7   Control (Path) 2 Occipital   11.7               Ctx       AD 5 SupTemporal Ctx   37.6   Control (Path) 3 Occipital   1.7               Ctx       AD 6 Inf Temporal Ctx   46.7   Control (Path) 4 Occipital   15.1               Ctx       AD 6 Sup Temporal Ctx   42.3   Control 1 Parietal Ctx   2.9       Control 1 Temporal Ctx   3.2   Control 2 Parietal Ctx   46.7       Control 2 Temporal Ctx   41.5   Control 3 Parietal Ctx   18.0       Control 3 Temporal Ctx   18.8   Control (Path) 1 Parietal   66.0               Ctx       Control 4 Temporal Ctx   8.9   Control (Path) 2 Parietal   15.4               Ctx       Control (Path) 1 Temporal   66.0   Control (Path) 3 Parietal   2.5       Ctx       Ctx       Control (Path) 2 Temporal   50.3   Control (Path) 4 Parietal   44.8       Ctx       Ctx                    
     [0860]               TABLE AEC                          General_screening_panel v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4445, Run       Ag4445, Run       Tissue Name   222693963   Tissue Name   222693963                                     Adipose   7.2   Renal ca. TK-10   5.5       Melanoma* Hs688(A).T   12.9   Bladder   13.2       Melanoma* Hs688(B).T   15.0   Gastric ca. (liver met.) NCI-   16.8               N87       Melanoma* M14   24.7   Gastric ca. KATO III   42.0       Melanoma* LOXIMVI   25.0   Colon ca. SW-948   8.7       Melanoma* SK-MEL-5   100.0   Colon ca. SW480   73.7       Squamous cell carcinoma   16.4   Colon ca.* (SW480 met)   29.3       SCC-4       SW620       Testis Pool   15.8   Colon ca. HT29   9.2       Prostate ca.* (bone met) PC-3   17.7   Colon ca. HCT-116   48.3       Prostate Pool   5.1   Colon ca. CaCo-2   29.7       Placenta   5.2   Colon cancer tissue   10.0       Uterus Pool   2.5   Colon ca. SW1116   8.5       Ovarian ca. OVCAR-3   20.7   Colon ca. Colo-205   8.4       Ovarian ca. SK-OV-3   20.3   Colon ca. SW-48   8.1       Ovarian ca. OVCAR-4   12.5   Colon Pool   6.3       Ovarian ca. OVCAR-5   29.9   Small Intestine Pool   4.5       Ovarian ca. IGROV-1   24.0   Stomach Pool   3.9       Ovarian ca. OVCAR-8   6.4   Bone Marrow Pool   2.5       Ovary   6.0   Fetal Heart   12.4       Breast ca. MCF-7   25.7   Heart Pool   6.0       Breast ca. MDA-MB-231   32.3   Lymph Node Pool   6.7       Breast ca. BT 549   56.6   Fetal Skeletal Muscle   5.7       Breast ca. T47D   62.4   Skeletal Muscle Pool   20.3       Breast ca. MDA-N   7.7   Spleen Pool   7.5       Breast Pool   5.3   Thymus Pool   6.7       Trachea   8.1   CNS cancer (glio/astro)   27.9               U87-MG       Lung   1.7   CNS cancer (glio/astro) U-   41.2               118-MG       Fetal Lung   15.2   CNS cancer (neuro;met)   14.3               SK-N-AS       Lung ca. NCI-N417   11.9   CNS cancer (astro) SF-539   22.1       Lung ca. LX-1   20.3   CNS cancer (astro) SNB-75   35.1       Lung ca. NCI-H146   8.4   CNS cancer (glio) SNB-19   21.5       Lung ca. SHP-77   36.6   CNS cancer (glio) SF-295   35.6       Lung ca. A549   32.3   Brain (Amygdala) Pool   12.6       Lung ca. NCI-H526   13.5   Brain (cerebellum)   9.3       Lung ca. NCI-H23   39.8   Brain (fetal)   10.9       Lung ca. NCI-H460   12.9   Brain (Hippocampus) Pool   13.0       Lung ca. HOP-62   22.1   Cerebral Cortex Pool   17.6       Lung ca. NCI-H522   15.4   Brain (Substantia nigra)   16.4               Pool       Liver   5.6   Brain (Thalamus) Pool   20.6       Fetal Liver   23.3   Brain (whole)   9.9       Liver ca. HepG2   11.3   Spinal Cord Pool   15.1       Kidney Pool   6.3   Adrenal Gland   16.8       Fetal Kidney   12.7   Pituitary gland Pool   6.4       Renal ca. 786-0   20.7   Salivary Gland   5.8       Renal ca. A498   11.0   Thyroid (female)   11.9       Renal ca. ACHN   18.7   Pancreatic ca. CAPAN2   15.1       Renal ca. UO-31   20.6   Pancreas Pool   7.8                    
     [0861]               TABLE AED                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag4445, Run       Ag4445, Run       Tissue Name   190826403   Tissue Name   190826403                                     Secondary Th1 act   68.3   HUVEC IL-1beta   66.4       Secondary Th2 act   62.4   HUVEC IFN gamma   38.2       Secondary Tr1 act   71.2   HUVEC TNF alpha + IFN   62.9               gamma       Secondary Th1 rest   30.1   HUVEC TNF alpha + IL4   54.0       Secondary Th2 rest   29.7   HUVEC IL-11   54.3       Secondary Tr1 rest   27.4   Lung Microvascular EC   60.3               none       Primary Th1 act   49.7   Lung Microvascular EC   64.6               TNF alpha + IL-1beta       Primary Th2 act   43.2   Microvascular Dermal EC   37.6               none       Primary Tr1 act   80.1   Microsvasular Dermal EC   40.3               TNF alpha + IL-1beta       Primary Th1 rest   30.8   Bronchial epithelium   43.8               TNF alpha + IL1beta       Primary Th2 rest   36.3   Small airway epithelium   35.6               none       Primary Tr1 rest   46.0   Small airway epithelium   38.4               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   49.3   Coronery artery SMC rest   58.6       act       CD45RO CD4 lymphocyte   63.3   Coronery artery SMC   40.1       act       TNF alpha + IL-1beta       CD8 lymphocyte act   64.6   Astrocytes rest   38.2       Secondary CD8 lymphocyte   51.8   Astrocytes TNF alpha + IL-   49.7       rest       1beta       Secondary CD8 lymphocyte   33.7   KU-812 (Basophil) rest   67.4       act       CD4 lymphocyte none   0.0   KU-812 (Basophil)   55.9               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   32.1   CCD1106 (Keratinocytes)   54.7       CH11       none       LAK cells rest   42.9   CCD1106 (Keratinocytes)   39.8               TNF alpha + IL-1beta       LAK cells IL-2   40.6   Liver cirrhosis   14.9       LAK cells IL-2 + IL-12   46.0   NCI-H292 none   60.3       LAK cells IL-2 + IFN gamma   65.5   NCI-H292 IL-4   69.7       LAK cells IL-2 + IL-18   50.3   NCI-H292 IL-9   84.1       LAK cells PMA/ionomycin   52.9   NCI-H292 IL-13   48.6       NK Cells IL-2 rest   65.1   NCI-H292 IFN gamma   59.0       Two Way MLR 3 day   37.4   HPAEC none   48.3       Two Way MLR 5 day   55.1   HPAEC TNF alpha + IL-1   84.7               beta       Two Way MLR 7 day   39.2   Lung fibroblast none   48.3       PBMC rest   23.2   Lung fibroblast TNF    59.5               alpha + IL-1beta       PBMC PWM   45.4   Lung fibroblast IL-4   50.0       PBMC PHA-L   61.6   Lung fibroblast IL-9   68.8       Ramos (B cell) none   39.0   Lung fibroblast IL-13   56.3       Ramos (B cell) ionomycin   36.6   Lung fibroblast IFN gamma   100.0       B lymphocytes PWM   46.3   Dermal fibroblast CCD1070   80.7               rest       B lymphocytes CD40L and   57.0   Dermal fibroblast CCD1070   88.9       IL-4       TNF alpha       EOL-1 dbcAMP   40.3   Dermal fibroblast CCD1070   35.6               IL-1beta       EOL-1 dbcAMP   53.2   Dermal fibroblast IFN   46.7       PMA/ionomycin       gamma       Dendritic cells none   58.6   Dermal fibroblast IL-4   55.9       Dendritic cells LPS   49.7   Dermal Fibroblasts rest   41.8       Dendritic cells anti-CD40   58.6   Neutrophils TNF a + LPS   17.9       Monocytes rest   26.2   Neutrophils rest   19.5       Monocytes LPS   55.1   Colon   23.5       Macrophages rest   35.6   Lung   32.1       Macrophages LPS   37.9   Thymus   49.7       HUVEC none   49.3   Kidney   85.9       HUVEC starved   66.4                    
     [0862] CNS_neurodegeneration_v1.0 Summary: Ag4445 This panel does not show differential expression of this gene in Alzheimer&#39;s disease. However, this expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.  
     [0863] General_screening_panel 13 v1.4 Summary: Ag4445 Highest expression of this gene is seen in a melanoma cell line (CT=22.4). This gene is widely expressed in this panel, with high levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. In addition, this gene is expressed at higher levels in fetal lung (CT=25) when compared to expression in adult lung (CT=28). Thus, expression of this gene could be used to differentiate between the fetal and adult source of this tissue. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.  
     [0864] Among tissues with metabolic function, this gene is expressed at high levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0865] This gene is also expressed at high levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0866] Panel 4.1D Summary: Ag4445 Highest expression of this gene is seen in IFN gamma treated lung fibroblasts (CT=28.1). This gene is also expressed at moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of fimctions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     AF. CG59975-01 and CG59975-02: Q9NO61-like Protein  
     [0867] Expression of gene CG59975-01 and variant CG59975-02 was assessed using the primer-probe set Ag3640, described in Table AFA. Results of the RTQ-PCR runs are shown in Tables AFB, AFC, AFD and AFE. Please note that CG59975-02 represents a full-length physical clone, verifying the CG59975-01 gene prediction.  
               TABLE AFA                          Probe Name Ag3640                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tgtttcaatctttcctcctcaa-3′   22   463   183               Probe   TET-5′-catttcaagctttgtgctgcctcttg-3′-TAMRA   26   512   184               Reverse   5′-ccacctggacaaagaggtagat-3′   22   538   185                  
 
     [0868]               TABLE AFB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag3640, Run       Ag3640, Run       Tissue Name   212315185   Tissue Name   212315185                                     AD 1 Hippo   9.1   Control (Path) 3 Temporal   8.7               Ctx       AD 2 Hippo   32.3   Control (Path) 4 Temporal   34.9               Ctx       AD 3 Hippo   8.1   AD 1 Occipital Ctx   20.4       AD 4 Hippo   8.7   AD 2 Occipital Ctx   0.0               (Missing)       AD 5 Hippo   87.7   AD 3 Occipital Ctx   8.1       AD 6 Hippo   55.5   AD 4 Occipital Ctx   39.0       Control 2 Hippo   50.0   AD 5 Occipital Ctx   54.0       Control 4 Hippo   14.0   AD 6 Occipital Ctx   25.0       Control (Path) 3 Hippo   8.1   Control 1 Occipital Ctx   4.7       AD 1 Temporal Ctx   22.2   Control 2 Occipital Ctx   81.8       AD 2 Temporal Ctx   34.2   Control 3 Occipital Ctx   16.0       AD 3 Temporal Ctx   4.7   Control 4 Occipital Ctx   9.7       AD 4 Temporal Ctx   19.1   Control (Path) 1 Occipital   100.0               Ctx       AD 5 Inf Temporal Ctx   98.6   Control (Path) 2 Occipital   12.1               Ctx       AD 5 SupTemporal Ctx   36.3   Control (Path) 3 Occipital   3.5               Ctx       AD 6 Inf Temporal Ctx   53.2   Control (Path) 4 Occipital   21.8               Ctx       AD 6 Sup Temporal Ctx   44.4   Control 1 Parietal Ctx   10.4       Control 1 Temporal Ctx   7.0   Control 2 Parietal Ctx   43.5       Control 2 Temporal Ctx   51.4   Control 3 Parietal Ctx   22.1       Control 3 Temporal Ctx   16.3   Control (Path) 1 Parietal Ctx   95.9       Control 3 Temporal Ctx   12.0   Control (Path) 2 Parietal Ctx   33.9       Control (Path) 1 Temporal   67.4   Control (Path) 3 Parietal Ctx   4.0       Ctx       Control (Path) 2 Temporal   49.0   Control (Path) 4 Parietal Ctx   40.6       Ctx                    
     [0869]               TABLE AFC                          General_screening_panel_v1.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag3640, Run       Ag3640, Run       Tissue Name   218234165   Tissue Name   218234165                                     Adipose   13.1   Renal ca. TK-10   33.4       Melanoma* Hs688(A).T   51.1   Bladder   34.2       Melanoma* Hs688(B).T   41.8   Gastric ca. (liver met.) NCI-   63.3               N87       Melanoma* M14   26.6   Gastric ca. KATO III   87.7       Melanoma* LOXIMVI   38.4   Colon ca. SW-948   11.6       Melanoma* SK-MEL-5   33.2   Colon ca. SW480   48.3       Squamous cell carcinoma   30.8   Colon ca.* (SW480 met)   23.2       SCC-4       SW620       Testis Pool   22.8   Colon ca. HT29   17.0       Prostate ca.* (bone met)   46.0   Colon ca. HCT-116   57.4       PC-3       Prostate Pool   18.6   Colon ca. CaCo-2   31.4       Placenta   13.9   Colon cancer tissue   29.7       Uterus Pool   4.9   Colon ca. SW1116   9.2       Ovarian ca. OVCAR-3   35.4   Colon ca. Colo-205   7.2       Ovarian ca. SK-OV-3   63.3   Colon ca. SW-48   15.6       Ovarian ca. OVCAR-4   24.8   Colon Pool   37.1       Ovarian ca. OVCAR-5   53.6   Small Intestine Pool   34.4       Ovarian ca. IGROV-1   24.3   Stomach Pool   27.2       Ovarian ca. OVCAR-8   15.0   Bone Marrow Pool   13.7       Ovary   19.5   Fetal Heart   18.7       Breast ca. MCF-7   63.3   Heart Pool   19.5       Breast ca. MDA-MB-231   66.4   Lymph Node Pool   40.1       Breast ca. BT 549   80.1   Fetal Skeletal Muscle   14.6       Breast ca. T47D   62.4   Skeletal Muscle Pool   19.1       Breast ca. MDA-N   21.0   Spleen Pool   18.9       Breast Pool   39.0   Thymus Pool   29.9       Trachea   32.5   CNS cancer (glio/astro)   39.5               U87-MG       Lung   9.0   CNS cancer (glio/astro) U-   68.8               118-MG       Fetal Lung   60.3   CNS cancer (neuro;met) SK-   29.3               N-AS       Lung ca. NCI-N417   5.1   CNS cancer (astro) SF-539   15.5       Lung ca. LX-1   33.0   CNS cancer (astro) SNB-75   93.3       Lung ca. NCI-H146   39.5   CNS cancer (glio) SNB-19   20.6       Lung ca. SHP-77   57.0   CNS cancer (glio) SF-295   100.0       Lung ca. A549   31.6   Brain (Amygdala) Pool   24.5       Lung ca. NCI-H526   14.1   Brain (cerebellum)   38.4       Lung ca. NCI-H23   50.7   Brain (fetal)   49.7       Lung ca. NCI-H460   19.1   Brain (Hippocampus) Pool   27.9       Lung ca. HOP-62   30.8   Cerebral Cortex Pool   36.6       Lung ca. NCI-H522   26.1   Brain (Substantia nigra)   33.0               Pool       Liver   2.4   Brain (Thalamus) Pool   39.8       Fetal Liver   22.7   Brain (whole)   29.9       Liver ca. HepG2   18.4   Spinal Cord Pool   24.7       Kidney Pool   55.5   Adrenal Gland   33.4       Fetal Kidney   37.9   Pituitary gland Pool   18.0       Renal ca. 786-0   35.8   Salivary Gland   9.9       Renal ca. A498   9.7   Thyroid (female)   16.3       Renal ca. ACHN   24.8   Pancreatic ca. CAPAN2   18.4       Renal ca. UO-31   45.4   Pancreas Pool   41.2                    
     [0870]               TABLE AFD                          Panel 4.1D                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag3640, Run       Ag3640, Run       Tissue Name   169975099   Tissue Name   169975099                                     Secondary Th1 act   30.4   HUVEC IL-1beta   42.6       Secondary Th2 act   49.7   HUVEC IFN gamma   49.0       Secondary Tr1 act   63.3   HUVEC TNF alpha + IFN   50.3               gamma       Secondary Th1 rest   22.5   HUVEC TNF alpha + IL4   62.0       Secondary Th2 rest   39.5   HUVEC IL-11   15.8       Secondary Tr1 rest   38.2   Lung Microvascular EC   77.9               none       Primary Th1 act   31.2   Lung Microvascular EC   84.7               TNF alpha + IL-1beta       Primary Th2 act   42.0   Microvascular Dermal EC   51.1               none       Primary Tr1 act   31.0   Microsvasular Dermal EC   34.4               TNF alpha + IL-1beta       Primary Th1 rest   28.3   Bronchial epithelium   34.6               TNF alpha + IL1beta       Primary Th2 rest   37.6   Small airway epithelium   20.4               none       Primary Tr1 rest   59.0   Small airway epithelium   62.0               TNF alpha + IL-1beta       CD45RA CD4 lymphocyte   46.7   Coronery artery SMC rest   27.7       act       CD45RO CD4 lymphocyte   37.9   Coronery artery SMC   35.6       act       TNF alpha + IL-1beta       CD8 lymphocyte act   42.3   Astrocytes rest   43.8       Secondary CD8 lymphocyte   34.2   Astrocytes TNF alpha + IL-   34.2       rest       1beta       Secondary CD8 lymphocyte   22.5   KU-812 (Basophil) rest   50.7       act       CD4 lymphocyte none   24.8   (KU-812 (Basophil)   100.0               PMA/ionomycin       2ry Th1/Th2/Tr1_anti-CD95   32.3   CCD1106 (Keratinocytes)   50.7       CH11       none       LAK cells rest   42.9   CCD1106 (Keratinocytes)   42.6               TNF alpha + IL-1beta       LAK cells IL-2   43.5   Liver cirrhosis   14.1       LAK cells IL-2 + IL-12   34.6   NCI-H292 none   30.4       LAK cells IL-2 + IFN gamma   62.4   NCI-H292 IL-4   50.3       LAK cells IL-2 + IL-18   67.4   NCI-H292 IL-9   65.1       LAK cells PMA/ionomycin   24.1   NCI-H292 IL-13   61.6       NK Cells IL-2 rest   48.3   NCI-H292 IFN gamma   47.3       Two Way MLR 3 day   62.0   HPAEC none   32.5       Two Way MLR 5 day   20.7   HPAEC TNF alpha + IL-1   70.7               beta       Two Way MLR 7 day   18.4   Lung fibroblast none   40.9       PBMC rest   15.5   Lung fibroblast TNF alpha +   23.3               IL-1beta       PBMC PWM   35.1   Lung fibroblast IL-4   52.1       PBMC PHA-L   29.3   Lung fibroblast IL-9   64.2       Ramos (B cell) none   36.9   Lung fibroblast IL-13   54.0       Ramos (B cell) ionomycin   34.2   Lung fibroblast IFN gamma   66.0       B lymphocytes PWM   31.4   Dermal fibroblast CCD1070   61.1               rest       B lymphocytes CD40L and   55.9   Dermal fibroblast CCD1070   98.6       IL-4       TNF alpha       EOL-1 dbcAMP   58.6   Dermal fibroblast CCD1070   32.1               IL-1beta       EOL-1 dbcAMP   74.2   Dermal fibroblast IFN   29.5       PMA/ionomycin       gamma       Dendritic cells none   34.4   Dermal fibroblast IL-4   43.5       Dendritic cells LPS   24.3   Dermal Fibroblasts rest   47.3       Dendritic cells anti-CD40   38.7   Neutrophils TNF a + LPS   2.0       Monocytes rest   49.3   Neutrophils rest   32.1       Monocytes LPS   95.3   Colon   16.6       Macrophages rest   33.0   Lung   16.0       Macrophages LPS   13.6   Thymus   74.2       HUVEC none   17.6   Kidney   41.5       HUVEC starved   41.5                    
     [0871]               TABLE AFE                          general oncology screening panel_v_2.4                                 Rel. Exp. (%)       Rel. Exp. (%)           Ag3640, Run       Ag3640, Run       Tissue Name   267752338   Tissue Name   267752338                                     Colon cancer 1   35.4   Bladder cancer NAT 2   0.4       Colon cancer NAT 1   12.4   Bladder cancer NAT 3   0.4       Colon cancer 2   20.2   Bladder cancer NAT 4   11.6       Colon cancer NAT 2   16.7   Adenocarcinoma of the   61.1               prostate 1       Colon cancer 3   39.8   Adenocarcinoma of the   6.5               prostate 2       Colon cancer NAT 3   32.8   Adenocarcinoma of the   39.2               prostate 3       Colon malignant cancer 4   56.3   Adenocarcinoma of the   31.2               prostate 4       Colon normal adjacent   6.7   Prostate cancer NAT 5   6.8       tissue 4       Lung cancer 1   17.8   Adenocarcinoma of the   15.3               prostate 6       Lung NAT 1   2.5   Adenocarcinoma of the   15.3               prostate 7       Lung cancer 2   96.6   Adenocarcinoma of the   3.6               prostate 8       Lung NAT 2   7.2   Adenocarcinoma of the   53.6               prostate 9       Squamous cell carcinoma 3   45.4   Prostate cancer NAT 10   3.0       Lung NAT 3   1.2   Kidney cancer 1   39.5       metastatic melanoma 1   41.2   KidneyNAT 1   15.6       Melanoma 2   5.3   Kidney cancer 2   69.3       Melanoma 3   7.4   Kidney NAT 2   37.6       metastatic melanoma 4   100.0   Kidney cancer 3   30.1       metastatic melanoma 5   82.9   Kidney NAT 3   11.0       Bladder cancer 1   2.3   Kidney cancer 4   32.1       Bladder cancer NAT 1   0.0   Kidney NAT 4   13.1       Bladder cancer 2   12.5                    
     [0872] CNS_neurodegeneration_v1.0 Summary: Ag3640 This panel does not show differential expression of this gene in Alzheimer&#39;s disease. However, this expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.  
     [0873] General_screening_panel 13 v1.4 Summary: Ag3640 Highest expression of this gene is seen in a brain cancer cell line (CT=26,7). This gene is widely expressed in this panel, with moderate expression seen in all cancer cell lines. In addition, this gene is expressed at much higher levels in fetal lung and liver tissue (CTs=27-29) when compared to expression in the adult counterpart (CTs=30-32). Thus, expression of this gene may be used to differentiate between the fetal and adult source of these tissues. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.  
     [0874] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0875] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0876] Panel 4.1D Summary: Ag3640 Highest expression of this gene is seen in the activated basophil cell line KU-812 (CT=27.5). This gene is also expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     [0877] General oncology screening panel_v — 2.4 Summary: Ag3640 This gene is widely expressed in this panel, with highest expression in melanoma (CT=27.7). In addition, this gene is more highly expressed in prostate, bladder, and kidney cancer than in the corresponding normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers. Furthemore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of melanoma, prostate, bladder, and kidney cancer.  
     AG. CG89947-01 and CG89947-02: Stra8  
     [0878] Expression of gene CG89947-01 and variant CG89947-02 was assessed using the primer-probe set Ag3698, described in Table AGA. Please note that CG89947-02 represents a full-length physical clone, verifying the CG89947-01 gene prediction.  
               TABLE AGA                          Probe Name Ag3698                                             Start   SEQ ID       Primers   Sequences   Length   Position   No               Forward   5′-ctcttcaacaacctcaggaaga-3′   22   161   186               Probe   TET-5′-tgtactctcagtctgatctcatagcctca-3′-TAMRA   29   186   187               Reverse   5′-ccttattcagaacctgccactt-3′   22   215   188                  
 
     AH. CG93366-02: Membrane Protein Kinase  
     [0879] Expression of gene CG93366-02 was assessed using the primer-probe set Ag3851, described in Table AHA. Results of the RTQ-PCR runs are shown in Tables AHB, AHC, AHD and AHE.  
               TABLE AHA                          Probe Name Ag3851                                             Start   SEQ ID       Primers   Sequences   Length   Position   No               Forward   5′-ttgaaagatgttggtggagaag-3′   22   985   189               Probe   TET-5′-ccagtctaatttacctcattcaaacagca-3′-TAMRA   29   1032   190               Reverse   5′-gcagctgcagacaactcatta-3′   21   1062   140                  
 
     [0880]               TABLE AHB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)               Ag3851, Run           Tissue Name   212186804                                         AD 1 Hippo   19.2           AD 2 Hippo   37.4           AD 3 Hippo   10.2           AD 4 Hippo   10.5           AD 5 hippo   90.8           AD 6 Hippo   52.9           Control 2 Hippo   29.5           Control 4 Hippo   22.8           Control (Path) 3 Hippo   12.8           AD 1 Temporal Ctx   27.2           AD 2 Temporal Ctx   49.3           AD 3 Temporal Ctx   12.9           AD 4 Temporal Ctx   33.2           AD 5 Inf Temporal Ctx   100.0           AD 5 SupTemporal Ctx   62.4           AD 6 Inf Temporal Ctx   71.2           AD 6 Sup Temporal Ctx   59.9           Control 1 Temporal Ctx   11.6           Control 2 Temporal Ctx   40.6           Control 3 Temporal Ctx   22.4           Control 4 Temporal Ctx   16.5           Control (Path) 1 Temporal   76.3           Ctx           Control (Path) 2 Temporal   51.8           Ctx           Control (Path) 3 Temporal   10.8           Ctx           Control (Path) 4 Temporal   50.7           Ctx           AD 1 Occipital Ctx   34.2           AD 2 Occipital Ctx   0.0           (Missing)           AD 3 Occipital Ctx   13.4           AD 4 Occipital Ctx   24.7           AD 5 Occipital Ctx   25.0           AD 6 Occipital Ctx   45.7           Control 1 Occipital Ctx   6.5           Control 2 Occipital Ctx   65.5           Control 3 Occipital Ctx   26.4           Control 4 Occipital Ctx   12.5           Control (Path) 1 Occipital   95.3           Ctx           Control (Path) 2 Occipital   23.0           Ctx           Control (Path) 3 Occipital   6.5           Ctx           Control (Path) 4 Occipital   26.8           Ctx           Control 1 Parietal Ctx   11.8           Control 2 Parietal Ctx   58.6           Control 3 Parietal Ctx   23.8           Control (Path) 1 Parietal   89.5           Ctx           Control (Path) 2 Parietal   37.9           Ctx           Control (Path) 3 Parietal   7.3           Ctx           Control (Path) 4 Parietal   57.0           Ctx                        
     [0881]               TABLE AHC                          General screening panel v1.4                                 Rel. Exp. (%)               Ag3851, Run           Tissue Name   213603718                                         Adipose   22.8           Melanoma* Hs688(A).T   62.4           Melanoma* Hs688(B).T   51.1           Melanoma* M14   14.8           Melanoma* LOXIMVI   6.7           Melanoma* SK-MEL-5   30.1           Squamous cell carcinoma   24.8           SCC-4           Testis Pool   20.4           Prostate ca.* (bone met) PC-3   26.8           Prostate Pool   15.5           Placenta   3.8           Uterus Pool   12.7           Ovarian ca. OVCAR-3   32.5           Ovarian ca. SK-OV-3   75.3           Ovarian ca. OVCAR-4   17.2           Ovarian ca. OVCAR-5   54.0           Ovarian ca. IGROV-1   20.7           Ovarian ca. OVCAR-8   11.8           Ovary   26.1           Breast ca. MCF-7   35.1           Breast ca. MDA-MB-23   19.5           Breast ca. BT 549   33.0           Breast ca. T47D   79.0           Breast ca. MDA-N   12.3           Breast Pool   38.2           Trachea   14.3           Lung   13.3           Fetal Lung   53.2           Lung ca. NCI-N417   3.7           Lung ca. LX-1   40.6           Lung ca. NCI-H146   5.1           Lung ca. SHP-77   29.7           Lung ca. A549   25.3           Lung ca. NCI-H526   5.8           Lung ca. NCI-H23   90.8           Lung ca. NCI-H460   32.5           Lung ca. HOP-62   31.6           Lung ca. NCI-H522   24.5           Liver   0.7           Fetal Liver   47.6           Liver ca. HepG2   50.0           Kidney Pool   50.0           Fetal Kidney   51.1           Renal ca. TK-10   41.2           Bladder   23.3           Gastric ca. (liver met.) NCI-N87   44.8           Gastric ca. KATO III   27.4           Colon ca. SW-948   6.3           Colon ca. SW480   24.1           Colon ca.* (SW480 met)   14.9           SW620           Colon ca. HT29   14.8           Colon ca. HCT-116   32.8           Colon ca. CaCo-2   55.9           Colon cancer tissue   15.2           Colon ca. SW1116   4.0           Colon ca. Colo-205   5.3           Colon ca. SW-48   7.0           Colon Pool   29.7           Small Intestine Pool   25.5           Stomach Pool   29.3           Bone Marrow Pool   8.1           Fetal Heart   12.2           Heart Pool   11.6           Lymph Node Pool   32.8           Fetal Skeletal Muscle   10.6           Skeletal Muscle Pool   16.8           Spleen Pool   28.7           Thymus Pool   33.7           CNS cancer (glio/astro)   38.2           U87-MG           CNS cancer (glio/astro) U-   36.9           118-MG           CNS cancer (neuro; met)   55.9           SK-N-AS           CNS cancer (astro) SF-539   10.7           CNS cancer (astro) SNB-75   21.9           CNS cancer (glio) SNB-19   15.8           CNS cancer (glio) SF-295   100.0           Brain (Amygdala) Pool   13.3           Brain (cerebellum)   19.2           Brain (fetal)   40.9           Brain (Hippocampus) Pool   20.9           Cerebral Cortex Pool   21.9           Brain (Substantia nigra)   23.8           Pool           Brain (Thalamus) Pool   31.2           Brain (whole)   23.0           Spinal Cord Pool   19.2           Adrenal Gland   10.4           Pituitary gland Pool   10.7           Renal ca. 786-0   39.0           Renal ca. A498   12.9           Renal ca. ACHN   15.9           Renal ca. UO-31   42.0           Salivary Gland   5.3           Thyroid (female)   11.7           Pancreatic ca. CAPAN2   36.3           Pancreas Pool   52.5                        
     [0882]               TABLE AHD                          Panel 4.1D                                 Rel. Exp. (%)               Ag3851, Run           Tissue Name   170121368                                         Secondary Th1 act   42.3           Secondary Th2 act   74.7           Secondary Tr1 act   84.7           Secondary Th1 rest   23.0           Secondary Th2 rest   52.5           Secondary Tr1 rest   40.6           Primary Th1 act   53.2           Primary Th2 act   55.9           Primary Tr1 act   39.5           Primary Th1 rest   37.4           Primary Th2 rest   62.0           Primary Tr1 rest   66.4           CD45RA CD4 lymphocyte   35.6           act           CD45RO CD4 lymphocyte   65.5           act           CD8 lymphocyte act   67.8           Secondary CD8 lymphocyte   33.9           rest           Secondary CD8 lymphocyte   21.0           act           CD4 lymphocyte none   42.3           2ry Th1/Th2/Tr1 anti-CD95   51.8           CH11           LAK cells rest   46.3           LAK cells IL-2   54.0           LAK cells IL-2 + IL-12   57.0           LAK cells IL-2 + IFN gamma   77.9           LAK cells IL-2 + IL- 18   78.5           LAK cells PMA/ionomycin   27.4           NK Cells IL-2 rest   54.3           Two Way MLR 3 day   80.7           Two Way MLR 5 day   41.2           Two Way MLR 7 day   31.2           PBMC rest   37.1           PBMC PWM   42.6           PBMC PHA-L   54.7           Ramos (B cell) none   47.3           Ramos (B cell) ionomycin   41.8           B lymphocytes PWM   37.9           B lymphocytes CD40L and   72.2           IL-4           EOL-1 dbcAMP   76.8           EOL-1 dbcAMP   100.0           PMA/ionomycin           Dendritic cells none   57.4           Dendritic cells LPS   30.4           Dendritic cells anti-CD40   61.1           Monocytes rest   51.8           Monocytes LPS   38.7           Macrophages rest   49.7           Macrophages LPS   14.5           HUVEC none   24.0           HUVEC starved   31.9           HUVEC IL-1beta   39.0           HUVEC IFN gamma   65.1           HUVEC TNF alpha + IFN   27.2           gamma           HUVEC TNF alpha + IL4   29.3           HUVEC IL- 11   24.5           Lung Microvascular EC   76.8           none           Lung Microvascular EC   44.4           TNFalpha + IL-1beta           Microvascular Dermal EC   45.4           none           Microsvasular Dermal EC   36.6           TNFalpha + IL-1beta           Bronchial epithelium   42.3           TNFalpha + IL-1beta           Small airway epithelium   14.2           none           Small airway epithelium   33.7           TNFalpha + IL-1beta           Coronery artery SMC rest   33.7           Coronery artery SMC   30.4           TNF alpha + IL-1beta           Astrocytes rest   41.2           Astrocytes TNF alpha + IL-   21.0           1beta           KU-812 (Basophil)rest   52.5           KU-812 (Basophil)   99.3           PMA/ionomycin           CCD1106 (Keratinocytes)   26.2           none           CCD1106 (Keratinocytes)   39.0           TNFalpha + IL-1beta           Liver cirrhosis   18.9           NCI-H292 none   43.2           NCI-H292 IL-4   42.6           NCI-H292 IL-9   71.2           NCI-H292 IL-13   68.8           NCI-H292 IFN gamma   71.7           HPAEC none   38.7           HPAEC TNF alpha + IL-1   47.0           beta           Lung fibroblast none   54.3           Lung fibroblast TNF alpha +   20.9           IL-1 beta           Lung fibroblast IL-4   56.6           Lung fibroblast IL-9   76.8           Lung fibroblast IL-13   50.0           Lung fibroblast IFN gamma   56.6           Dermal fibroblast CCD1070   33.0           rest           Dermal fibroblast CCD1070   62.4           TNF alpha           Dermal fibroblast CCD1070   21.3           IL-1 beta           Dermal fibroblast IFN   36.1           gamma           Dermal fibroblast IL-4   82.4           Dermal Fibroblasts rest   65.5           Neutrophils TNFa + LPS   0.7           Neutrophils rest   8.3           Colon   16.4           Lung   33.7           Thymus   84.7           Kidney   78.5                        
     [0883]               TABLE AHE                          general oncology screening panel_v_2.4                                 Rel. Exp. (%)               Ag3851, Run           Tissue Name   268036588                                         Colon cancer 1   21.6           Colon cancer NAT 1   7.8           Colon cancer 2   10.7           Colon cancer NAT 2   10.2           Colon cancer 3   21.9           Colon cancer NAT 3   15.6           Colon malignant cancer 4   31.2           Colon normal adjacent tissue 4   4.9           Lung cancer 1   8.7           Lung NAT 1   2.9           Lung cancer 2   39.5           Lung NAT 2   4.1           Squamous cell carcinoma 3   18.0           Lung NAT 3   0.5           metastatic melanoma 1   35.6           Melanoma 2   1.2           Melanoma 3   4.1           metastatic melanoma 4   66.0           metastatic melanoma 5   100.0           Bladder cancer 1   2.7           Bladder cancer NAT 1   0.0           Bladder cancer 2   8.8           Bladder cancer NAT 2   1.1           Bladder cancer NAT 3   0.5           Bladder cancer NAT 4   4.2           Adenocarcinoma of the   57.4           prostate 1           Adenocarcinoma of the   3.5           prostate 2           Adenocarcinoma of the   16.4           prostate 3           Adenocarcinoma of the   14.7           prostate 4           Prostate cancer NAT 5   1.9           Adenocarcinoma of the   4.0           prostate 6           Adenocarcinoma of the   5.8           prostate 7           Adenocarcinoma of the   2.2           prostate 8           Adenocarcinoma of the   33.9           prostate 9           Prostate cancer NAT 10   2.2           Kidney cancer 1   21.3           Kidney NAT 1   12.6           Kidney cancer 2   32.1           Kidney NAT 2   27.2           Kidney cancer 3   34.4           Kidney NAT 3   10.4           Kidney cancer 4   16.0           Kidney NAT 4   6.3                        
     [0884] CNS_neurodegeneration_v1.0 Summary: Ag3851 This panel does not show differential expression of this gene in Alzheimer&#39;s disease. However, this expression profile confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.  
     [0885] General_screening_panel 13 v1.4 Summary: Ag3851 Highest expression of this gene is seen in a brain cancer cell line (CT=26.5). This gene is widely expressed in this panel, with high to moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancers. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.  
     [0886] Among tissues with metabolic function, this gene is expressed at high to moderate levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0887] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer&#39;s disease, Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0888] In addition, this gene is expressed at much higher levels in fetal liver tissue (CT=27.5) when compared to expression in the adult counterpart (CT=33.7). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue. The relative overexpression of this gene in fetal liver suggests that the protein product may enhance growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of this gene could be useful in treatment of liver disease.  
     [0889] Panel 4.1D Summary: Ag3851 This gene is expressed at moderate levels in a wide range of cell types of significance in the immune response in health and disease, with highest expression in activated eosinophils (CT=28.8). These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel 13 v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     [0890] General oncology screening panel_v — 2.4 Summary: Ag3851 Highest expression of this gene is seen in melanoma (CT=26.5). In addition, higher levels of expression of this gene are seen in lung, colon, and prostate cancer when compared to expression in normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers. Furthemore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of lung, colon and prostate cancer.  
     Example D  
     [0891] Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences  
     [0892] Variant sequences are also included in this application. A variant sequence can include a single nucleotide polymorphism (SNP). A SNP can, in some instances, be referred to as a “cSNP” to denote that the nucleotide sequence containing the SNP originates as a cDNA. A SNP can arise in several ways. For example, a SNP may be due to a substitution of one nucleotide for another at the polymorphic site. Such a substitution can be either a transition or a transversion. A SNP can also arise from a deletion of a nucleotide or an insertion of a nucleotide, relative to a reference allele. In this case, the polymorphic site is a site at which one allele bears a gap with respect to a particular nucleotide in another allele. SNPs occurring within genes may result in an alteration of the amino acid encoded by the gene at the position of the SNP. Intragenic SNPs may also be silent, when a codon including a SNP encodes the same amino acid as a result of the redundancy of the genetic code. SNPs occurring outside the region of a gene, or in an intron within a gene, do not result in changes in any amino acid sequence of a protein but may result in altered regulation of the expression pattern. Examples include alteration in temporal expression, physiological response regulation, cell type expression regulation, intensity of expression, and stability of transcribed message.  
     [0893] SeqCalling assemblies produced by the exon linking process were selected and extended using the following criteria. Genomic clones having regions with 98% identity to all or part of the initial or extended sequence were identified by BLASTN searches using the relevant sequence to query human genomic databases. The genomic clones that resulted were selected for further analysis because this identity indicates that these clones contain the genomic locus for these SeqCalling assemblies. These sequences were analyzed for putative coding regions as well as for similarity to the known DNA and protein sequences. Programs used for these analyses include Grail, Genscan, BLAST, HMMER, FASTA, Hybrid and other relevant programs.  
     [0894] Some additional genomic regions may have also been identified because selected SeqCalling assemblies map to those regions. Such SeqCalling sequences may have overlapped with regions defined by homology or exon prediction. They may also be included because the location of the fragment was in the vicinity of genomic regions identified by similarity or exon prediction that had been included in the original predicted sequence. The sequence so identified was manually assembled and then may have been extended using one or more additional sequences taken from CuraGen Corporation&#39;s human SeqCalling database. SeqCalling fragments suitable for inclusion were identified by the CuraTools™ program SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed.  
     [0895] The regions defined by the procedures described above were then manually integrated and corrected for apparent inconsistencies that may have arisen, for example, from miscalled bases in the original fragments or from discrepancies between predicted exon junctions, EST locations and regions of sequence similarity, to derive the final sequence disclosed herein. When necessary, the process to identify and analyze SeqCalling assemblies and genomic clones was reiterated to derive the full length sequence (Alderborn et al., Determination of Single Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000).  
     [0896] 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.  
     [0897] SNPs for NOV6a Cytosolic Phosphoprotein Protein (CG101904-01)  
                                                  Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13377350   197   T   C   26   Val   Ala       13379270   1640   G   A   507   Arg   His                  
 
     [0898] SNPs for NOV9a NEURABIN 1-like  Homo sapiens  Proteins (CG102595-01)  
                                                  Nucleotides   Amino Acids                                         Variant   Base Position of           Base Position of               No.   SNP   Wild-type   Variant   SNP   Wild-type   Variant               13379218   3159   A   G   1033   Thr   Thr       13379217   3267   A   G   1069   Leu   Leu                  
 
     [0899] SNPs for NOV11a Septin 6 (KIAA0128)-like Protein (CG102801-01)  
                                                  Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified               13379273   876   G   A   269   Cys   Tyr       13379274   1032   A   G   321   Gln   Arg                  
 
     [0900] SNPs NOV12a RIM24C-like  Homo sapiens  Proteins (CG102899-01)  
                                                  Nucleotides   Amino Acids                                         Variant   Base Position of           Base Position of               No.   SNP   Wild-type   Variant   SNP   Wild-type   Variant               13379220   3993   T   C   1311   Ala   Ala                  
 
     [0901] SNPs for NOV13a Cell Growth Regulator Falkor-like Protein (CG105284-01)  
                                                  Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13377532   187   C   A   46   Pro   Thr       13377533   1142   A   G   364   Tyr   Cys                  
 
     [0902] SNPs for NOV17a Ankyrin-like Q9GKW8-like  Homo sapiens  Protein (CG105638-01)  
                                                  Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13379275   100   A   T   22   Arg   Trp       13379276   217   C   T   61   His   Tyr       13379277   827   A   G   264   His   Arg                  
 
     [0903] SNPs for NOV22a Amyloid Beta A4 Precursor Protein-Binding Family B Member 2-like  Homo sapiens  Protein (CG106868-01)  
                                                  Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified               13379281   685   G   A   179   Arg   Gln                  
 
     [0904] SPNs for NOV 26a Intracellular Signaling Protein-like  Homo sapiens  Proteins (CG109649-01)  
                                                  Nucleotides   Amino Acids                                         Variant   Base Position of           Base Position of               No.   SNP   Wild-type   Variant   SNP   Wild-type   Variant               13379254   228   C   T   56   Thr   Thr       13379253   300   C   T   80   Ile   Ile                  
 
     [0905] SPNs for NOV31a VP3 Domain-containing Protein-like  Homo sapiens  Proteins (CG110063-01)  
                                                  Nucleotides   Amino Acids                                         Variant   Base Position of           Base Position of               No.   SNP   Wild-type   Variant   SNP   Wild-type   Variant                                                 13379257   68   T   C   12   Pro   Pro       13379258   470   G   T   146   Leu   Phe                  
 
     [0906] SNPs for NOV37a Stra8-like  Homo sapiens  Proteins (CG89947-01)  
                                                  Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13375011   86   C   T   21   Gln   End       13375012   160   G   A   45   Ala   Ala       13375013   176   A   G   51   Arg   Gly                  
 
     [0907] SNPs for NOV38a Membrane Protein Kinase-like Proteins (CG93366-02)  
                                                  Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified               13379282   1656   C   T   552   Gly   Gly                  
 
     Other Embodiments  
     [0908] 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.  
     [0909] The claims presented are representative of the inventions disclosed herein. Other, unclaimed inventions are also contemplated. Applicants reserve the right to pursue such inventions in later claims.