Patent Publication Number: US-2004043929-A1

Title: Novel proteins and nucleic acids encoding same

Description:
RELATED APPLICATIONS  
     [0001] This application is a continuation-in-part application of U.S. Ser. No. 09/746,491, filed on Dec. 20, 2000; U.S. Ser. No. 10/005,041, filed Dec. 4, 2001; U.S. Ser. No. 10/023,681, filed Dec. 18, 2001; U.S. Ser. No. 10/024,212, filed Dec. 18, 2001; U.S. Ser. No. 10/055,569, filed Oct. 26, 2001; U.S. Ser. No. 10/080,334, filed Feb. 21, 2002; U.S. Ser. No. 10/092,900, filed Mar. 7, 2002; U.S. Ser. No. 10/136,826, filed May 1, 2002; U.S. Ser. No. 10/236,417v, filed Sep. 6, 2002; and claims priority to provisional patent applications U.S. S. No. 60/345,092, filed Jan. 4, 2002; U.S. S. No. 60/345,219, filed Jan. 4, 2002; U.S. S. No. 60/348,804, filed Jan. 14, 2002; U.S. S. No. 60/349,182, filed Jan. 16, 2002; U.S. S. No. 60/349,733, filed Jan. 17, 2002; U.S. S. No. 60/349,839, filed Jan. 17, 2002; U.S. S. No. 60/350,263, filed Jan. 18, 2002; U.S. S. No. 60/351,977, filed Jan. 24, 2002; U.S. S. No. 60/354,783, filed Feb. 5, 2002; U.S. S. No. 60/358,629, filed Feb. 21, 2002; and U.S. S. No. 60/359,860, filed Feb. 27, 2002; U.S. S. No. 60/385,969, filed Jun. 5, 2002; U.S. S. No. 60/389,531, filed on Jun. 18, 2002; U.S. S. No. 60/389,604, filed on Jun. 18, 2002; U.S. S. No. 60/402,150, filed Aug. 9, 2002; U.S. S. No. 60/402,834, filed Aug. 12, 2002; U.S. S. No. 60/402,867, filed Aug. 12, 2002; and U.S. S. No. 60/406,398, filed Aug. 27, 2002; each of which is incorporated herein by reference in its entirety. 
    
    
     
       FIELD OF TIHE INVENTION  
       [0002] The present invention relates to novel polypeptides that are targets of small molecule drugs and that have properties related to stimulation of biochemical or physiological responses in a cell, a tissue, an organ or an organism. More particularly, the novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions.  
       BACKGROUND  
       [0003] Eukaryotic cells are characterized by biochemical and physiological processes which under normal conditions are exquisitely balanced to achieve the preservation and propagation of the cells. When such cells are components of multicellular organisms such as vertebrates, or more particularly organisms such as mammals, the regulation of the biochemical and physiological processes involves intricate signaling pathways. Frequently, such signaling pathways involve extracellular signaling proteins, cellular receptors that bind the signaling proteins and signal transducing components located within the cells.  
       [0004] Signaling proteins may be classified as endocrine effectors, paracrine effectors or autocrine effectors. Endocrine effectors are signaling molecules secreted by a given organ into the circulatory system, which are then transported to a distant target organ or tissue. The target cells include the receptors for the endocrine effector, and when the endocrine effector binds, a signaling cascade is induced. Paracrine effectors involve secreting cells and receptor cells in close proximity to each other, for example two different classes of cells in the same tissue or organ. One class of cells secretes the paracrine effector, which then reaches the second class of cells, for example by diffusion through the extracellular fluid. The second class of cells contains the receptors for the paracrine effector; binding of the effector results in induction of the signaling cascade that elicits the corresponding biochemical or physiological effect. Autocrine effectors are highly analogous to paracrine effectors, except that the same cell type that secretes the autocrine effector also contains the receptor. Thus the autocrine effector binds to receptors on the same cell, or on identical neighboring cells. The binding process then elicits the characteristic biochemical or physiological effect.  
       [0005] Signaling processes may elicit a variety of effects on cells and tissues including by way of nonlimiting example induction of cell or tissue proliferation, suppression of growth or proliferation, induction of differentiation or maturation of a cell or tissue, and suppression of differentiation or maturation of a cell or tissue.  
       [0006] Many pathological conditions involve dysregulation of expression of important effector proteins. In certain classes of pathologies the dysregulation is manifested as diminished or suppressed level of synthesis and secretion of protein effectors. In other classes of pathologies the dysregulation is manifested as increased or up-regulated level of synthesis and secretion of protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by altered or mis-regulated levels of a protein effector of interest. Therefore there is a need to assay for the level of the protein effector of interest in a biological sample from such a subject, and to compare the level with that characteristic of a nonpathological condition. There also is a need to provide the protein effector as a product of manufacture. Administration of the effector to a subject in need thereof is useful in treatment of the pathological condition. Accordingly, there is a need for a method of treatment of a pathological condition brought on by a diminished or suppressed levels of the protein effector of interest. In addition, there is a need for a method of treatment of a pathological condition brought on by a increased or up-regulated levels of the protein effector of interest.  
       [0007] Small molecule targets have been implicated in various disease states or pathologies. These targets may be proteins, and particularly enzymatic proteins, which are acted upon by small molecule drugs for the purpose of altering target function and achieving a desired result. Cellular, animal and clinical studies can be performed to elucidate the genetic contribution to the etiology and pathogenesis of conditions in which small molecule targets are implicated in a variety of physiologic, pharmacologic or native states. These studies utilize the core technologies at CuraGen Corporation to look at differential gene expression, protein-protein interactions, large-scale sequencing of expressed genes and the association of genetic variations such as, but not limited to, single nucleotide polymorphisms (SNPs) or splice variants in and between biological samples from experimental and control groups. The goal of such studies is to identify potential avenues for therapeutic intervention in order to prevent, treat the consequences or cure the conditions.  
       [0008] In order to treat diseases, pathologies and other abnormal states or conditions in which a mammalian organism has been diagnosed as being, or as being at risk for becoming, other than in a normal state or condition, it is important to identify new therapeutic agents. Such a procedure includes at least the steps of identifying a target component within an affected tissue or organ, and identifying a candidate therapeutic agent that modulates the functional attributes of the target. The target component may be any biological macromolecule implicated in the disease or pathology. Commonly-the target is a polypeptide or protein with specific functional attributes. Other classes of macromolecule may be a nucleic acid, a polysaccharide, a lipid such as a complex lipid or a glycolipid; in addition a target may be a sub-cellular structure or extra-cellular structure that is comprised of more than one of these classes of macromolecule. Once such a target has been identified, it may be employed in a screening assay in order to identify favorable candidate therapeutic agents from among a large population of substances or compounds.  
       [0009] In many cases the objective of such screening assays is to identify small molecule candidates; this is commonly approached by the use of combinatorial methodologies to develop the population of substances to be tested. The implementation of high throughput screening methodologies is advantageous when working with large, combinatorial libraries of compounds.  
       SUMMARY OF THE INVENTION  
       [0010] The invention includes nucleic acid sequences and the novel polypeptides they encode. The novel nucleic acids and polypeptides are referred to herein as NOVX, or NOV1, NOV2, NOV3, etc., nucleic acids and polypeptides. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid, which represents the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 66, or polypeptide sequences, which represents the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 66.  
       [0011] In one aspect, the invention provides an isolated polypeptide comprising a mature form of a NOVX amino acid. One example is a variant of a mature form of a NOVX amino acid sequence, 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. The amino acid can be, for example, a NOVX amino acid sequence or a variant of a NOVX amino acid sequence, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed. The invention also includes fragments of any of these. In another aspect, the invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof.  
       [0012] Also included in the invention is a NOVX polypeptide that is a naturally occurring allelic variant of a NOVX sequence. In one embodiment, the allelic variant includes an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a NOVX nucleic acid sequence. In another embodiment, the NOVX polypeptide is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution. In one embodiment, the invention discloses a method for determining the presence or amount of the NOVX polypeptide in a sample. The method involves the steps of: providing a sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the NOVX polypeptide, thereby determining the presence or amount of the NOVX polypeptide in the sample. In another embodiment, the invention provides a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide in a mammalian subject. This method involves the steps of: measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in the sample of the first step to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.  
       [0013] In a further embodiment, the invention includes a method of identifying an agent that binds to a NOVX polypeptide. This method involves the steps of: introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide. In various embodiments, the agent is a cellular receptor or a downstream effector.  
       [0014] In another aspect, the invention provides 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 NOVX polypeptide. The method involves the steps of: providing a cell expressing the NOVX polypeptide 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. In another aspect, the invention describes a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with the NOVX polypeptide. This method involves the following steps: administering a test compound to a test animal at increased risk for a pathology associated with the NOVX polypeptide, wherein the test animal recombinantly expresses the NOVX polypeptide. This method involves the steps of measuring the activity of the NOVX polypeptide in the test animal after administering the compound of step; and comparing the activity of the protein in the test animal with the activity of the NOVX polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of, or predisposition to, a pathology associated with the NOVX polypeptide. In one embodiment, the test animal is a recombinant test animal that expresses a test protein transgene or expresses the transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein the promoter is not the native gene promoter of the transgene. In another aspect, the invention includes a method for modulating the activity of the NOVX polypeptide, the method comprising introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.  
       [0015] The invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof. In a preferred embodiment, the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant. In another embodiment, the nucleic acid encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence. In one embodiment, the NOVX nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 66, or a complement of the nucleotide sequence. In another aspect, the invention provides a vector or a cell expressing a NOVX nucleotide sequence.  
       [0016] In one embodiment, the invention discloses a method for modulating the activity of a NOVX polypeptide. The method includes the steps of: introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide. In another embodiment, the invention includes an isolated NOVX nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising a NOVX amino acid sequence or a variant of a mature form of the NOVX amino acid sequence, 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. In another embodiment, the invention includes an amino acid sequence that is a variant of the NOVX amino acid sequence, 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.  
       [0017] In one embodiment, the invention discloses a NOVX nucleic acid fragment encoding at least a portion of a NOVX polypeptide or any variant of the 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. In another embodiment, the invention includes the complement of any of the NOVX nucleic acid molecules or a naturally occurring allelic nucleic acid variant. In another embodiment, the invention discloses a NOVX nucleic acid molecule that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the invention discloses a NOVX nucleic acid, wherein the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence.  
       [0018] In another aspect, the invention includes a NOVX nucleic acid, wherein one or more nucleotides in the NOVX nucleotide sequence is changed to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In one embodiment, the invention discloses a nucleic acid fragment of the NOVX nucleotide sequence and a nucleic acid fragment wherein one or more nucleotides in the NOVX nucleotide sequence 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. In another embodiment, the invention includes a nucleic acid molecule wherein the nucleic acid molecule hybridizes under stringent conditions to a NOVX nucleotide sequence or a complement of the NOVX nucleotide sequence. In one embodiment, the invention includes a nucleic acid molecule, wherein the sequence is changed such that no more than 15% of the nucleotides in the coding sequence differ from the NOVX nucleotide sequence or a fragment thereof.  
       [0019] In a further aspect, the invention includes a method for determining the presence or amount of the NOVX nucleic acid in a sample. The method involves the steps of: providing the sample; introducing the sample to a probe that binds to the nucleic acid molecule; and determining the presence or amount of the probe bound to the NOVX nucleic acid molecule, thereby determining the presence or amount of the NOVX nucleic acid molecule in the sample. In one embodiment, the presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.  
       [0020] In another aspect, the invention discloses a method for determining the presence of or predisposition to a disease associated with altered levels of the NOVX nucleic acid molecule of in a first mammalian subject. The method involves the steps of: measuring the amount of NOVX nucleic acid in a sample from the first mammalian subject; and comparing the amount of the nucleic acid in the sample of step (a) to the amount of NOVX nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.  
       [0021] In an aspect, the present invention provides a method of identifying a candidate therapeutic agent for treating a disease, pathology, or an abnormal state or condition using a target entity having a specific association with the disease. This method includes:  
       [0022] (1) identification of a target biopolymer associated with the disease, pathology, or abnormal state or condition;  
       [0023] (2) contacting the biopolymer with at least one chemical compound; and  
       [0024] (3) identifying a compound that binds to the biopolymer as a candidate therapeutic agent.  
       [0025] In some embodiments of this method, the chemical compound is a member of a combinatorial library of compounds; the contacting in step (b) is conducted on one or more replicate samples of the biopolymer; and the replicate sample is contacted with at least one member of the combinatorial library. In additional embodiments of this method, the biopolymer is included within a cell and is functionally expressed therein. In still a further advantageous embodiment, the binding of the compound modulates the function of the biopolymer, and it is the modulation that provides the identification that the compound is a potential therapeutic agent. In yet further significant embodiments of this method, the target biopolymer is a polypeptide.  
       [0026] In a second aspect of the invention, a method for identifying a pharmaceutical agent for treating a disease, pathology, or an abnormal state or condition is provided. The second method includes the steps of:  
       [0027] (1) identifying a candidate therapeutic agent for treating said disease, pathology, or abnormal state or condition by the method described in the preceding paragraph;  
       [0028] (2) contacting a biological sample associated with the disease, pathology, or abnormal state or condition with the candidate therapeutic agent;  
       [0029] (3) determining whether the candidate induces an effect on the biological sample associated with a therapeutic response therein; and  
       [0030] (4) identifying a candidate exerting such an effect as a pharmaceutical agent.  
       [0031] In some embodiments of the second method, the biological sample includes a cell, a tissue or organ, or is a nonhuman mammal.  
       [0032] The present invention discloses novel associations of proteins and polypeptides and the nucleic acids that encode them with various diseases or pathologies. The proteins and related proteins that are similar to them, are encoded by a cDNA and/or by genomic DNA. The proteins, polypeptides and their cognate nucleic acids were identified by CuraGen Corporation in certain cases. The human Sulfonylurea 2A protein encoded by CG154077 and any variants, thereof, are suitable as diagnostic markers, targets for an antibody therapeutic and targets for small molecule drugs. As such the current invention embodies the use of recombinantly expressed and/or endogenously expressed protein in various screens to identify such therapeutic antibodies and/or therapeutic small molecules.  
       [0033] 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.  
       [0034] Other features and advantages of the invention will be apparent from the following detailed description and claims.  
       DETAILED DESCRIPTION OF THE INVENTION  
       [0035] 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   SEQ ID NO           NOVX   Internal   (nucleic   (amino       Assignment   Identification   acid)   acid)   Homology                                         NOV1a   CG108945-01   1   2   Human Protein       NOV1b   CG108945-02   3   4   Human Protein       NOV2a   CG112559-03   5   6   Ubiquinone       NOV2b   CG112559-02   7   8   Ubiquinone       NOV2c   CG112559-01   9   10   Ubiquinone       NOV3a   CG115757-01   11   12   Dynactin       NOV3b   CG115757-02   13   14   Dynactin       NOV4a   CG120781-01   15   16   Myosin heavy chain       NOV4b   CG120781-03   17   18   Myosin heavy chain       NOV4c   CG120781-04   19   20   Myosin heavy chain       NOV4d   CG120781-02   21   22   Myosin heavy chain       NOV5a   CG122634-01   23   24   Kinesin heavy chain       NOV6a   CG125312-01   25   26   Myosin       NOV7a   CG134632-01   27   28   dUTP pyrophosphatase       NOV7b   CG134632-02   29   30   dUTP pyrophosphatase       NOV7c   CG134632-03   31   32   dUTP pyrophosphatase       NOV8a   CG148411-01   33   34   multicatalytic endopeptidase                       complex       NOV8b   CG148411-02   35   36   multicatalytic endopeptidase                       complex       NOV9a   CG154077-01   37   38   Sulfonylurea receptor 2       NOV10a   CG155759-02   39   40   Seven transmembrane helix receptor       NOV10b   CG155759-01   41   42   Seven transmembrane helix receptor       NOV11a   CG155882-01   43   44   Seven transmembrane helix receptor       NOV12a   CG159399-01   45   46   WUGSC:H_DJ0539M06.4 protein       NOV12b   CG159399-02   47   48   WUGSC:H_DJ0539M06.4 protein       NOV13a   CG167853-01   49   50   Cytoplasmic acetyl-CoA hydrolase 1       NOV14a   CG167873-01   51   52   P2X purinoceptor 5       NOV14b   CG167873-02   53   54   P2X purinoceptor 5       NOV15a   CG167893-01   55   56   Human Protein       NOV16a   CG169088-01   57   58   Ca2 + transporting ATPase       NOV17a   CG169201-01   59   60   ATPase       NOV18a   CG50303-01   61   62   Seven transmembrane helix receptor       NOV18b   CG50303-03   63   64   Seven transmembrane helix receptor       NOV18c   276863879   65   66   Seven transmembrane helix receptor       NOV18d   276863902   67   68   Seven transmembrane helix receptor       NOV18e   CG50303-01   69   70   Seven transmembrane helix receptor       NOV18f   CG50303-02   71   72   Seven transmembrane helix receptor       NOV19a   CG54092-03   73   74   GTPase regulator       NOV19b   CG54092-01   75   76   GTPase regulator       NOV19c   CG54092-03   77   78   GTPase regulator       NOV19d   262770591   79   80   GTPase regulator       NOV19e   262770609   81   82   GTPase regulator       NOV19f   296457330   83   84   GTPase regulator       NOV19g   CG54092-02   85   86   GTPase regulator       NOV20a   CG55798-04   87   88   G-protein coupled receptor       NOV20b   CG55798-02   89   90   G-protein coupled receptor       NOV20c   265722099   91   92   G-protein coupled receptor       NOV20d   265725302   93   94   G-protein coupled receptor       NOV20e   CG55798-01   95   96   G-protein coupled receptor       NOV20f   CG55798-03   97   98   G-protein coupled receptor       NOV21a   CG55838-05   99   100   Mitogen-activated protein kinase                       kinase 2       NOV21b   CG55838-03   101   102   Mitogen-activated protein kinase                       kinase 2       NOV21c   CG55838-02   103   104   Mitogen-activated protein kinase                       kinase 2       NOV21d   309394046   105   106   Mitogen-activated protein kinase                       kinase 2       NOV21e   CG55838-04   107   108   Mitogen-activated protein kinase                       kinase 2       NOV21f   CG55838-01   109   110   Mitogen-activated protein kinase                       kinase 2       NOV21g   CG55838-06   111   112   Mitogen-activated protein kinase                       kinase 2       NOV22a   CG56618-02   113   114   Heat shock protein       NOV22b   CG56618-03   115   116   Heat shock protein       NOV22c   CG56618-04   117   118   Heat shock protein       NOV22d   CG56618-01   119   120   Heat shock protein       NOV23a   CG57509-01   121   122   Calpain       NOV23b   CG57509-02   123   124   Calpain       NOV24a   CG59522-02   125   126   Human protein       NOV24b   CG59522-01   127   128   Human protein       NOV25a   CG90474-02   129   130   Human uncoupling protein       NOV25b   CG90474-01   131   132   Human uncoupling protein                  
 
       [0036] Table A indicates the homology of NOVX polypeptides to known protein families. Thus, the nucleic acids and polypeptides, antibodies and related compounds according to the invention corresponding to a NOVX as identified in column 1 of Table A will be useful in therapeutic and diagnostic applications implicated in, for example, pathologies and disorders associated with the known protein families identified in column 5 of Table A.  
       [0037] Pathologies, diseases, disorders and condition and the like that are associated with NOVX sequences include, but are not limited to, e.g., cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, metabolic disturbances associated with obesity, transplantation, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn&#39;s disease; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, 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, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation and fertility.  
       [0038] 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.  
       [0039] 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.  
       [0040] 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.  
       [0041] The NOVX nucleic acids and polypeptides are also useful for detecting specific cell types. Details of the expression analysis for each NOVX are presented in Example C. Accordingly, the NOVX nucleic acids, polypeptides, antibodies and related compounds according to the invention will have diagnostic and therapeutic applications in the detection of a variety of diseases with differential expression in normal vs. diseased tissues, e.g. detection of a variety of cancers. SNP analysis for each NOVX, if applicable, is presented in Example D.  
       [0042] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.  
       [0043] NOVX Clones  
       [0044] 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.  
       [0045] 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.  
       [0046] The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. These include serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo (vi) a biological defense weapon.  
       [0047] 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 66; (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 66, 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 66; (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 66 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).  
       [0048] 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 66; (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 66 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 66; (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 66, 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 66 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.  
       [0049] 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 66; (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 66 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 66; 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 66 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.  
       [0050] NOVX Nucleic Acids and Polypeptides  
       [0051] 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.  
       [0052] A NOVX nucleic acid can encode a mature NOVX polypeptide. As used herein, a “mature” form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full-length gene product encoded by the corresponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein. The product “mature” form arises, by way of nonlimiting example, as a result of one or more naturally occurring processing steps that may take place within the cell (e.g., host cell) in which the gene product arises. Examples of such processing steps leading to a “mature” form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+1 to residue N remaining. Further as used herein, a “mature” form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination of any of them.  
       [0053] The term “probe”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), about 100 nt, or as many as approximately, e.g., 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single-stranded or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.  
       [0054] The term “isolated” nucleic acid molecule, as used herein, is a nucleic acid that is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5′- and 3′-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.). Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium, or of chemical precursors or other chemicals.  
       [0055] A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, or a complement of this nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, 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.)  
       [0056] A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template with appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to NOVX nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.  
       [0057] As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.  
       [0058] 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 66, or a portion of this nucleotide sequence (e.g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of a NOVX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, that it can hydrogen bond with few or no mismatches to the nucleotide sequence shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, thereby forming a stable duplex.  
       [0059] 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.  
       [0060] A “fragment” provided herein is defined as a sequence of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, and is at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice.  
       [0061] 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.  
       [0062] A “derivative” is a nucleic acid sequence or amino acid sequence formed from the native compounds either directly, by modification or partial substitution. An “analog” is a nucleic acid sequence or amino acid sequence that has a structure similar to, but not identical to, the native compound, e.g. they differs from it in respect to certain components or side chains. Analogs may be synthetic or derived from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. A “homolog” is a nucleic acid sequence or amino acid sequence of a particular gene that is derived from different species.  
       [0063] Derivatives and analogs may be full length or other than full length. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the proteins under stringent, moderately stringent, or low stringent conditions. See e.g. Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley &amp; Sons, New York, N.Y., 1993, and below.  
       [0064] A “homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences include those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for a NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein. Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.  
       [0065] A NOVX polypeptide is encoded by the open reading frame (“ORF”) of a NOVX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG “start” codon and terminates with one of the three “stop” codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bona fide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.  
       [0066] The nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g. from other tissues, as well as NOVX homologues from other vertebrates. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66; or of a naturally occurring mutant of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66.  
       [0067] Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In various embodiments, the probe has a detectable label attached, e.g. the label can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express a NOVX protein, such as by measuring a level of a NOVX-encoding nucleic acid in a sample of cells from a subject e.g., detecting NOVX mRNA levels or determining whether a genomic NOVX gene has been mutated or deleted.  
       [0068] “A polypeptide having a biologically-active portion of a NOVX polypeptide” refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a “biologically-active portion of NOVX” can be prepared by isolating a portion of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, that encodes a polypeptide having a NOVX biological activity (the biological activities of the NOVX proteins are described below), expressing the encoded portion of NOVX protein (e.g., by recombinant expression in vitro) and assessing the activity of the encoded portion of NOVX.  
       [0069] NOVX Nucleic Acid and Polypeptide Variants  
       [0070] The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 66.  
       [0071] In addition to the human NOVX nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, it will be appreciated by those skilled in the art that DNA sequence polymorphisms that lead to changes in the amino acid sequences of the NOVX polypeptides may exist within a population (e.g., the human population). Such genetic polymorphism in the NOVX genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms “gene” and “recombinant gene” refer to nucleic acid molecules comprising an open reading frame (ORF) encoding a NOVX protein, preferably a vertebrate NOVX protein. Such natural allelic variations can typically result in 1-5% variance in the nucleotide sequence of the NOVX genes. Any and all such nucleotide variations and resulting amino acid polymorphisms in the NOVX polypeptides, which are the result of natural allelic variation and that do not alter the functional activity of the NOVX polypeptides, are intended to be within the scope of the invention.  
       [0072] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from a human SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, 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.  
       [0073] 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 66. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences at least about 65% homologous to each other typically remain hybridized to each other.  
       [0074] 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.  
       [0075] As used herein, the phrase “stringent hybridization conditions” refers to conditions under which a probe, primer or oligonucleotide will hybridize to its target sequence, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures than shorter sequences. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium. Typically, stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes, primers or oligonucleotides (e.g., 10 nt to 50 nt) and at least about 60° C. for longer probes, primers and oligonucleotides. Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide.  
       [0076] 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 a sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, 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).  
       [0077] 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 66, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6×SSC, 5×Reinhardt&#39;s solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55° C., followed by one or more washes in 1×SSC, 0.1% SDS at 37° C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley &amp; Sons, NY, and Krieger, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY.  
       [0078] In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley &amp; Sons, 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.  
       [0079] Conservative Mutations  
       [0080] In addition to naturally-occurring allelic variants of NOVX sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, thereby leading to changes in the amino acid sequences of the encoded NOVX protein, without altering the functional ability of that NOVX protein. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 66. 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 not particularly amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.  
       [0081] Another aspect of the invention pertains to nucleic acid molecules encoding NOVX proteins that contain changes in amino acid residues that are not essential for activity. Such NOVX proteins differ in amino acid sequence from SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 40% homologous to the amino acid sequences of SEQ ID NO:2n, wherein n is an integer between 1 and 66. 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 66; more preferably at least about 70% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 66; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 66; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 66; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 66.  
       [0082] An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 66, 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 66, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.  
       [0083] Mutations can be introduced any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more 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 non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity. Following mutagenesis of a nucleic acid of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.  
       [0084] 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.  
       [0085] In one embodiment, a mutant NOVX protein can be assayed for (i) the ability to form protein:protein interactions with other NOVX proteins, other cell-surface proteins, or biologically-active portions thereof, (ii) complex formation between a mutant NOVX protein and a NOVX ligand; or (iii) the ability of a mutant NOVX protein to bind to an intracellular target protein or biologically-active portion thereof; (e.g. avidin proteins).  
       [0086] 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).  
       [0087] Interfering RNA  
       [0088] In one aspect of the invention, NOVX gene expression can be attenuated by RNA interference. One approach well-known in the art is short interfering RNA (siRNA) mediated gene silencing where expression products of a NOVX gene are targeted by specific double stranded NOVX derived siRNA nucleotide sequences that are complementary to at least a 19-25 nt long segment of the NOVX gene transcript, including the 5′ untranslated (UT) region, the ORF, or the 3′ UT region. See, e.g., PCT applications WO00/44895, WO99/32619, WO01/75164, WO01/92513, WO01/29058, WO01/89304, WO02/16620, and WO02/29858, each incorporated by reference herein in their entirety. Targeted genes can be a NOVX gene, or an upstream or downstream modulator of the NOVX gene. Nonlimiting examples of upstream or downstream modulators of a NOVX gene include, e.g., a transcription factor that binds the NOVX gene promoter, a kinase or phosphatase that interacts with a NOVX polypeptide, and polypeptides involved in a NOVX regulatory pathway.  
       [0089] According to the methods of the present invention, NOVX gene expression is silenced using short interfering RNA. A NOVX polynucleotide according to the invention includes a siRNA polynucleotide. Such a NOVX siRNA can be obtained using a NOVX polynucleotide sequence, for example, by processing the NOVX ribopolynucleotide sequence in a cell-free system, such as but not limited to a Drosophila extract, or by transcription of recombinant double stranded NOVX RNA or by chemical synthesis of nucleotide sequences homologous to a NOVX sequence. See, e.g., Tuschl, Zamore, Lehmann, Bartel and Sharp (1999), Genes &amp; Dev. 13: 3191-3197, incorporated herein by reference in its entirety. When synthesized, a typical 0.2 micromolar-scale RNA synthesis provides about 1 milligram of siRNA, which is sufficient for 1000 transfection experiments using a 24-well tissue culture plate format.  
       [0090] The most efficient silencing is generally observed with siRNA duplexes composed of a 21-nt sense strand and a 21-nt antisense strand, paired in a manner to have a 2-nt 3′ overhang. The sequence of the 2-nt 3′ overhang makes an additional small contribution to the specificity of siRNA target recognition. The contribution to specificity is localized to the unpaired nucleotide adjacent to the first paired bases. In one embodiment, the nucleotides in the 3′ overhang are ribonucleotides. In an alternative embodiment, the nucleotides in the 3′ overhang are deoxyribonucleotides. Using 2′-deoxyribonucleotides in the 3′ overhangs is as efficient as using ribonucleotides, but deoxyribonucleotides are often cheaper to synthesize and are most likely more nuclease resistant.  
       [0091] A contemplated recombinant expression vector of the invention comprises a NOVX DNA molecule cloned into an expression vector comprising operatively-linked regulatory sequences flanking the NOVX sequence in a manner that allows for expression (by transcription of the DNA molecule) of both strands. An RNA molecule that is antisense to NOVX mRNA is transcribed by a first promoter (e.g., a promoter sequence 3′ of the cloned DNA) and an RNA molecule that is the sense strand for the NOVX mRNA is transcribed by a second promoter (e.g., a promoter sequence 5′ of the cloned DNA). The sense and antisense strands may hybridize in vivo to generate siRNA constructs for silencing of the NOVX gene. Alternatively, two constructs can be utilized to create the sense and anti-sense strands of a siRNA construct. Finally, cloned DNA can encode a construct having secondary structure, wherein a single transcript has both the sense and complementary antisense sequences from the target gene or genes. In an example of this embodiment, a hairpin RNAi product is homologous to all or a portion of the target gene. In another example, a hairpin RNAi product is a siRNA. The regulatory sequences flanking the NOVX sequence may be identical or may be different, such that their expression may be modulated independently, or in a temporal or spatial manner.  
       [0092] In a specific embodiment, siRNAs are transcribed intracellularly by cloning the NOVX gene templates into a vector containing, e.g., a RNA pol III transcription unit from the smaller nuclear RNA (snRNA) U6 or the human RNase P RNA H1. One example of a vector system is the GeneSuppressor™ RNA Interference kit (commercially available from Imgenex). The U6 and H1 promoters are members of the type III class of Pol III promoters. The +1 nucleotide of the U6-like promoters is always guanosine, whereas the +1 for H1 promoters is adenosine. The termination signal for these promoters is defined by five consecutive thymidines. The transcript is typically cleaved after the second uridine. Cleavage at this position generates a 3′ UU overhang in the expressed siRNA, which is similar to the 3′ overhangs of synthetic siRNAs. Any sequence less than 400 nucleotides in length can be transcribed by these promoter, therefore they are ideally suited for the expression of around 21-nucleotide siRNAs in, e.g., an approximately 50-nucleotide RNA stem-loop transcript.  
       [0093] A siRNA vector appears to have an advantage over synthetic siRNAs where long term knock-down of expression is desired. Cells transfected with a siRNA expression vector would experience steady, long-term mRNA inhibition. In contrast, cells transfected with exogenous synthetic siRNAs typically recover from mRNA suppression within seven days or ten rounds of cell division. The long-term gene silencing ability of siRNA expression vectors may provide for applications in gene therapy.  
       [0094] In general, siRNAs are chopped from longer dsRNA by an ATP-dependent ribonuclease called DICER. DICER is a member of the RNase III family of double-stranded RNA-specific endonucleases. The siRNAs assemble with cellular proteins into an endonuclease complex. In vitro studies in Drosophila suggest that the siRNAs/protein complex (siRNP) is then transferred to a second enzyme complex, called an RNA-induced silencing complex (RISC), which contains an endoribonuclease that is distinct from DICER. RISC uses the sequence encoded by the antisense siRNA strand to find and destroy mRNAs of complementary sequence. The siRNA thus acts as a guide, restricting the ribonuclease to cleave only mRNAs complementary to one of the two siRNA strands.  
       [0095] A NOVX mRNA region to be targeted by siRNA is generally selected from a desired NOVX sequence beginning 50 to 100 nt downstream of the start codon. Alternatively, 5′ or 3′ UTRs and regions nearby the start codon can be used but are generally avoided, as these may be richer in regulatory protein binding sites. UTR-binding proteins and/or translation initiation complexes may interfere with binding of the siRNP or RISC endonuclease complex. An initial BLAST homology search for the selected siRNA sequence is done against an available nucleotide sequence library to ensure that only one gene is targeted. Specificity of target recognition by siRNA duplexes indicate that a single point mutation located in the paired region of an siRNA duplex is sufficient to abolish target mRNA degradation. See, Elbashir et al. 2001 EMBO J. 20(23):6877-88. Hence, consideration should be taken to accommodate SNPs, polymorphisms, allelic variants or species-specific variations when targeting a desired gene.  
       [0096] In one embodiment, a complete NOVX siRNA experiment includes the proper negative control. A negative control siRNA generally has the same nucleotide composition as the NOVX siRNA but lack significant sequence homology to the genome. Typically, one would scramble the nucleotide sequence of the NOVX siRNA and do a homology search to make sure it lacks homology to any other gene.  
       [0097] Two independent NOVX siRNA duplexes can be used to knock-down a target NOVX gene. This helps to control for specificity of the silencing effect. In addition, expression of two independent genes can be simultaneously knocked down by using equal concentrations of different NOVX siRNA duplexes, e.g., a NOVX siRNA and an siRNA for a regulator of a NOVX gene or polypeptide. Availability of siRNA-associating proteins is believed to be more limiting than target mRNA accessibility.  
       [0098] A targeted NOVX region is typically a sequence of two adenines (AA) and two thymidines (TT) divided by a spacer region of nineteen (N19) residues (e.g., AA(N19)TT). A desirable spacer region has a G/C-content of approximately 30% to 70%, and more preferably of about 50%. If the sequence AA(N19)TT is not present in the target sequence, an alternative target region would be AA(N21). The sequence of the NOVX sense siRNA corresponds to (N19)TT or N21, respectively. In the latter case, conversion of the 3′ end of the sense siRNA to TT can be performed if such a sequence does not naturally occur in the NOVX polynucleotide. The rationale for this sequence conversion is to generate a symmetric duplex with respect to the sequence composition of the sense and antisense 3′ overhangs. Symmetric 3′ overhangs may help to ensure that the siRNPs are formed with approximately equal ratios of sense and antisense target RNA-cleaving siRNPs. See, e.g., Elbashir, Lendeckel and Tuschl (2001). Genes &amp; Dev. 15: 66-200, incorporated by reference herein in its entirely. The modification of the overhang of the sense sequence of the siRNA duplex is not expected to affect targeted mRNA recognition, as the antisense siRNA strand guides target recognition.  
       [0099] Alternatively, if the NOVX target mRNA does not contain a suitable AA(N21) sequence, one may search for the sequence NA(N21). Further, the sequence of the sense strand and antisense strand may still be synthesized as 5′ (N19)TT, as it is believed that the sequence of the 3′-most nucleotide of the antisense siRNA does not contribute to specificity. Unlike antisense or ribozyme technology, the secondary structure of the target mRNA does not appear to have a strong effect on silencing. See, Harborth, et al. (2001) J. Cell Science 114: 4557-4565, incorporated by reference in its entirety.  
       [0100] Transfection of NOVX siRNA duplexes can be achieved using standard nucleic acid transfection methods, for example, OLIGOFECTAMINE Reagent (commercially available from Invitrogen). An assay for NOVX gene silencing is generally performed approximately 2 days after transfection. No NOVX gene silencing has been observed in the absence of transfection reagent, allowing for a comparative analysis of the wild-type and silenced NOVX phenotypes. In a specific embodiment, for one well of a 24-well plate, approximately 0.84 μg of the siRNA duplex is generally sufficient. Cells are typically seeded the previous day, and are transfected at about 50% confluence. The choice of cell culture media and conditions are routine to those of skill in the art, and will vary with the choice of cell type. The efficiency of transfection may depend on the cell type, but also on the passage number and the confluency of the cells. The time and the manner of formation of siRNA-liposome complexes (e.g. inversion versus vortexing) are also critical. Low transfection efficiencies are the most frequent cause of unsuccessful NOVX silencing. The efficiency of transfection needs to be carefully examined for each new cell line to be used. Preferred cell are derived from a mammal, more preferably from a rodent such as a rat or mouse, and most preferably from a human. Where used for therapeutic treatment, the cells are preferentially autologous, although non-autologous cell sources are also contemplated as within the scope of the present invention.  
       [0101] For a control experiment, transfection of 0.84 μg single-stranded sense NOVX siRNA will have no effect on NOVX silencing, and 0.84 μg antisense siRNA has a weak silencing effect when compared to 0.84 μg of duplex siRNAs. Control experiments again allow for a comparative analysis of the wild-type and silenced NOVX phenotypes. To control for transfection efficiency, targeting of common proteins is typically performed, for example targeting of lamin A/C or transfection of a CMV-driven EGFP-expression plasmid (e.g. commercially available from Clontech). In the above example, a determination of the fraction of lamin A/C knockdown in cells is determined the next day by such techniques as immunofluorescence, Western blot, Northern blot or other similar assays for protein expression or gene expression. Lamin A/C monoclonal antibodies may be obtained from Santa Cruz Biotechnology.  
       [0102] Depending on the abundance and the half life (or turnover) of the targeted NOVX polynucleotide in a cell, a knock-down phenotype may become apparent after 1 to 3 days, or even later. In cases where no NOVX knock-down phenotype is observed, depletion of the NOVX polynucleotide may be observed by immunofluorescence or Western blotting. If the NOVX polynucleotide is still abundant after 3 days, cells need to be split and transferred to a fresh 24-well plate for re-transfection. If no knock-down of the targeted protein is observed, it may be desirable to analyze whether the target mRNA (NOVX or a NOVX upstream or downstream gene) was effectively destroyed by the transfected siRNA duplex. Two days after transfection, total RNA is prepared, reverse transcribed using a target-specific primer, and PCR-amplified with a primer pair covering at least one exon-exon junction in order to control for amplification of pre-mRNAs. RT/PCR of a non-targeted mRNA is also needed as control. Effective depletion of the mRNA yet undetectable reduction of target protein may indicate that a large reservoir of stable NOVX protein may exist in the cell. Multiple transfection in sufficiently long intervals may be necessary until the target protein is finally depleted to a point where a phenotype may become apparent. If multiple transfection steps are required, cells are split 2 to 3 days after transfection. The cells may be transfected immediately after splitting.  
       [0103] An inventive therapeutic method of the invention contemplates administering a NOVX siRNA construct as therapy to compensate for increased or aberrant NOVX expression or activity. The NOVX ribopolynucleotide is obtained and processed into siRNA fragments, or a NOVX siRNA is synthesized, as described above. The NOVX siRNA is administered to cells or tissues using known nucleic acid transfection techniques, as described above. A NOVX siRNA specific for a NOVX gene will decrease or knockdown NOVX transcription products, which will lead to reduced NOVX polypeptide production, resulting in reduced NOVX polypeptide activity in the cells or tissues.  
       [0104] The present invention also encompasses a method of treating a disease or condition associated with the presence of a NOVX protein in an individual comprising administering to the individual an RNAi construct that targets the mRNA of the protein (the mRNA that encodes the protein) for degradation. A specific RNAi construct includes a siRNA or a double stranded gene transcript that is processed into siRNAs. Upon treatment, the target protein is not produced or is not produced to the extent it would be in the absence of the treatment.  
       [0105] Where the NOVX gene function is not correlated with a known phenotype, a control sample of cells or tissues from healthy individuals provides a reference standard for determining NOVX expression levels. Expression levels are detected using the assays described, e.g., RT-PCR, Northern blotting, Western blotting, ELISA, and the like. A subject sample of cells or tissues is taken from a mammal, preferably a human subject, suffering from a disease state. The NOVX ribopolynucleotide is used to produce siRNA constructs, that are specific for the NOVX gene product. These cells or tissues are treated by administering NOVX siRNA&#39;s to the cells or tissues by methods described for the transfection of nucleic acids into a cell or tissue, and a change in NOVX polypeptide or polynucleotide expression is observed in the subject sample relative to the control sample, using the assays described. This NOVX gene knockdown approach provides a rapid method for determination of a NOVX minus (NOVX − ) phenotype in the treated subject sample. The NOVX −  phenotype observed in the treated subject sample thus serves as a marker for monitoring the course of a disease state during treatment.  
       [0106] In specific embodiments, a NOVX siRNA is used in therapy. Methods for the generation and use of a NOVX siRNA are known to those skilled in the art. Example techniques are provided below.  
       [0107] Production of RNAs  
       [0108] Sense RNA (ssRNA) and antisense RNA (asRNA) of NOVX are produced using known methods such as transcription in RNA expression vectors. In the initial experiments, the sense and antisense RNA are about 500 bases in length each. The produced ssRNA and asRNA (0.5 μM) in 10 mM Tris-HCl (pH 7.5) with 20 mM NaCl were heated to 95° C. for 1 min then cooled and annealed at room temperature for 12 to 16 h. The RNAs are precipitated and resuspended in lysis buffer (below). To monitor annealing, RNAs are electrophoresed in a 2% agarose gel in TBE buffer and stained with ethidium bromide. See, e.g., Sambrook et al., Molecular Cloning. Cold Spring Harbor Laboratory Press, Plainview, N.Y. (1989).  
       [0109] Lysate Preparation  
       [0110] Untreated rabbit reticulocyte lysate (Ambion) are assembled according to the manufacturer&#39;s directions. dsRNA is incubated in the lysate at 300 C for 10 min prior to the addition of mRNAs. Then NOVX mRNAs are added and the incubation continued for an additional 60 min. The molar ratio of double stranded RNA and mRNA is about 200:1. The NOVX mRNA is radiolabeled (using known techniques) and its stability is monitored by gel electrophoresis.  
       [0111] In a parallel experiment made with the same conditions, the double stranded RNA is internally radiolabeled with a  32 P-ATP. Reactions are stopped by the addition of 2× proteinase K buffer and deproteinized as described previously (Tuschl et al., Genes Dev., 13:3191-3197 (1999)). Products are analyzed by electrophoresis in 15% or 18% polyacrylamide sequencing gels using appropriate RNA standards. By monitoring the gels for radioactivity, the natural production of 10 to 25 nt RNAs from the double stranded RNA can be determined.  
       [0112] The band of double stranded RNA, about 21-23 bps, is eluded. The efficacy of these 21-23 mers for suppressing NOVX transcription is assayed in vitro using the same rabbit reticulocyte assay described above using 50 nanomolar of double stranded 21-23 mer for each assay. The sequence of these 21-23 mers is then determined using standard nucleic acid sequencing techniques.  
       [0113] RNA Preparation  
       [0114] 21 nt RNAs, based on the sequence determined above, are chemically synthesized using Expedite RNA phosphoramidites and thymidine phosphoramidite (Proligo, Germany). Synthetic oligonucleotides are deprotected and gel-purified (Elbashir, Lendeckel, &amp; Tuschl, Genes &amp; Dev. 15, 188-200 (2001)), followed by Sep-Pak C18 cartridge (Waters, Milford, Mass., USA) purification (Tuschl, et al., Biochemistry, 32:11658-11668 (1993)).  
       [0115] These RNAs (20 μM) single strands are incubated in annealing buffer (100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate) for 1 min at 90° C. followed by 1 h at 37° C.  
       [0116] Cell Culture A cell culture known in the art to regularly express NOVX is propagated using standard conditions. 24 hours before transfection, at approx. 80% confluency, the cells are trypsinized and diluted 1:5 with fresh medium without antibiotics (1-3×105 cells/ml) and transferred to 24-well plates (500 ml/well). Transfection is performed using a commercially available lipofection kit and NOVX expression is monitored using standard techniques with positive and negative control. A positive control is cells that naturally express NOVX while a negative control is cells that do not express NOVX. Base-paired 21 and 22 nt siRNAs with overhanging 3′ ends mediate efficient sequence-specific mRNA degradation in lysates and in cell culture. Different concentrations of siRNAs are used. An efficient concentration for suppression in vitro in mammalian culture is between 25 nM to 100 nM final concentration. This indicates that siRNAs are effective at concentrations that are several orders of magnitude below the concentrations applied in conventional antisense or ribozyme gene targeting experiments.  
       [0117] The above method provides a way both for the deduction of NOVX siRNA sequence and the use of such siRNA for in vitro suppression. In vivo suppression may be performed using the same siRNA using well known in vivo transfection or gene therapy transfection techniques.  
       [0118] Antisense Nucleic Acids  
       [0119] 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 66, or fragments, analogs or derivatives thereof. An “antisense” nucleic acid comprises a nucleotide sequence that is complementary to a “sense” nucleic acid encoding a protein (e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of a NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 66, or antisense nucleic acids complementary to a NOVX nucleic acid sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, are additionally provided.  
       [0120] In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding a NOVX protein. The term “coding region” refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid molecule is antisense to a “noncoding region” of the coding strand of a nucleotide sequence encoding the NOVX protein. The term “noncoding region” refers to 5′ and 3′ sequences which flank the coding region that are not translated into amino acids (i.e., also referred to as 5′ and 3′ untranslated regions).  
       [0121] 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).  
       [0122] Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-carboxymethylaminomethyl-2-thiouridine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).  
       [0123] The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.  
       [0124] 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.  
       [0125] Ribozymes and PNA Moieties  
       [0126] 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.  
       [0127] In one embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988.  Nature  334: 585-591) can be used to catalytically cleave NOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. A ribozyme having specificity for a NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of a NOVX cDNA disclosed herein (i.e., SEQ ID NO:2n-1, wherein n is an integer between 1 and 66). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a NOVX-encoding mRNA. See, e.g., U.S. Pat. No. 4,987,071 to Cech, et al. and U.S. Pat. No. 5,116,742 to Cech, et al. NOVX mRNA can also be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Bartel et al., (1993)  Science  261:1411-1418.  
       [0128] 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.  
       [0129] In various embodiments, the NOVX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, e.g., Hyrup, et al., 1996.  Bioorg Med Chem  4: 5-23. As used herein, the terms “peptide nucleic acids” or “PNAs” refer to nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleotide bases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomer can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra; Perry-O&#39;Keefe, et al., 1996 . Proc. Natl. Acad. Sci. USA  93: 14670-14675.  
       [0130] 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).  
       [0131] In another embodiment, PNAs of NOVX can be modified, e.g., to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras of NOVX can be generated that may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes (e.g., RNase H and DNA polymerases) to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleotide bases, and orientation (see, Hyrup, et al., 1996. supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al., 1996. supra and Finn, et al., 1996 . Nucl Acids Res  24: 3357-3363. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g., 5′-(4-methoxytrityl)amino-5′-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5′ end of DNA. See, e.g., Mag, et al., 1989 . Nucl Acid Res  17: 5973-5988. PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5′ PNA segment and a 3′ DNA segment. See, e.g., Finn, et al., 1996. supra. Alternatively, chimeric molecules can be synthesized with a 5′ DNA segment and a 3′ PNA segment. See, e.g., Petersen, et al., 1975 . Bioorg. Med. Chem. Lett.  5: 1119-11124.  
       [0132] In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al., 1989 . Proc. Natl. Acad. Sci. U.S.A.  86: 6553-6556; Lemaitre, et al., 1987 . Proc. Natl. Acad. Sci.  84: 648-652; PCT Publication No. WO88/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (see, e.g., Krol, et al., 1988. BioTechniques 6:958-976) or intercalating agents (see, e.g., Zon, 1988 . Pharm. Res.  5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.  
       [0133] NOVX Polypeptides  
       [0134] A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in any one of SEQ ID NO:2n, wherein n is an integer between 1 and 66. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in any one of SEQ ID NO:2n, wherein n is an integer between 1 and 66, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.  
       [0135] In general, a NOVX variant that preserves NOVX-like function includes any variant in which residues at a particular position in the sequence have been substituted by other amino acids, and further include the possibility of inserting an additional residue or residues between two residues of the parent protein as well as the possibility of deleting one or more residues from the parent sequence. Any amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.  
       [0136] One aspect of the invention pertains to isolated NOVX proteins, and biologically-active portions thereof, or derivatives, fragments, analogs or homologs thereof. Also provided are polypeptide fragments suitable for use as immunogens to raise anti-NOVX antibodies. In one embodiment, native NOVX proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, NOVX proteins are produced by recombinant DNA techniques. Alternative to recombinant expression, a NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.  
       [0137] 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.  
       [0138] 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.  
       [0139] Biologically-active portions of NOVX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the NOVX proteins (e.g., the amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 66) that include fewer amino acids than the full-length NOVX proteins, and exhibit at least one activity of a NOVX protein. Typically, biologically-active portions comprise a domain or motif with at least one activity of the NOVX protein. A biologically-active portion of a NOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length.  
       [0140] 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.  
       [0141] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 66. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 66, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 66, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below. Accordingly, in another embodiment, the NOVX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 66, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1 and 66.  
       [0142] Determining Homology Between Two or More Sequences  
       [0143] 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”).  
       [0144] The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970 . J Mol Biol  48: 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison: GAP creation penalty of 5.0 and GAP extension penalty of 0.3, the coding region of the analogous nucleic acid sequences referred to above exhibits a degree of identity preferably of at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66.  
       [0145] 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.  
       [0146] Chimeric and Fusion Proteins The invention also provides NOVX chimeric or fusion proteins. As used herein, a NOVX “chimeric protein” or “fusion protein” comprises a NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An “NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a NOVX protein of SEQ ID NO:2n, wherein n is an integer between 1 and 66, whereas a “non-NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a protein that is not substantially homologous to the NOVX protein, e.g., a protein that is different from the NOVX protein and that is derived from the same or a different organism. Within a NOVX fusion protein the NOVX polypeptide can correspond to all or a portion of a NOVX protein. In one embodiment, a NOVX fusion protein comprises at least one biologically-active portion of a NOVX protein. In another embodiment, a NOVX fusion protein comprises at least two biologically-active portions of a NOVX protein. In yet another embodiment, a NOVX fusion protein comprises at least three biologically-active portions of a NOVX protein. Within the fusion protein, the term “operatively-linked” is intended to indicate that the NOVX polypeptide and the non-NOVX polypeptide are fused in-frame with one another. The non-NOVX polypeptide can be fused to the N-terminus or C-terminus of the NOVX polypeptide.  
       [0147] 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.  
       [0148] In another embodiment, the fusion protein is a NOVX protein containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells), expression and/or secretion of NOVX can be increased through use of a heterologous signal sequence.  
       [0149] In yet another embodiment, the fusion protein is a NOVX-immunoglobulin fusion protein in which the NOVX sequences are fused to sequences derived from a member of the immunoglobulin protein family. The NOVX-immunoglobulin fusion proteins of the invention can be incorporated into pharmaceutical compositions and administered to a subject to inhibit an interaction between a NOVX ligand and a NOVX protein on the surface of a cell, to thereby suppress NOVX-mediated signal transduction in vivo. The NOVX-immunoglobulin fusion proteins can be used to affect the bioavailability of a NOVX cognate ligand. Inhibition of the NOVX ligand/NOVX interaction may be useful therapeutically for both the treatment of proliferative and differentiative disorders, as well as modulating (e.g. promoting or inhibiting) cell survival. Moreover, the NOVX-immunoglobulin fusion proteins of the invention can be used as immunogens to produce anti-NOVX antibodies in a subject, to purify NOVX ligands, and in screening assays to identify molecules that inhibit the interaction of NOVX with a NOVX ligand.  
       [0150] A NOVX chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e.g., by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, e.g., Ausubel, et al. (eds.) CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley &amp; Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). A NOVX-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the NOVX protein.  
       [0151] NOVX Agonists and Antagonists  
       [0152] 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.  
       [0153] 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.  
       [0154] Polypeptide Libraries  
       [0155] In addition, libraries of fragments of the NOVX protein coding sequences can be used to generate a variegated population of NOVX fragments for screening and subsequent selection of variants of a NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a NOVX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with 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.  
       [0156] 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.  
       [0157] Anti-NOVX Antibodies  
       [0158] 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, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as 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.  
       [0159] An isolated protein of the invention intended to serve as an antigen, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that immunospecifically bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation. The full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as immunogens. An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 66, 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. In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX that is located on the surface of the protein, e.g., a hydrophilic region. A hydrophobicity analysis of the human NOVX protein sequence will indicate which regions of a NOVX polypeptide are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production. As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, 1981 , Proc. Nat. Acad. Sci. USA  78: 3824-3828; Kyte and Doolittle 1982 , J. Mol. Biol.  157: 105-142, each incorporated herein by reference in their entirety. Antibodies that are specific for one or more domains within an antigenic protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.  
       [0160] The term “epitope” includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. A NOVX polypeptide or a fragment thereof comprises at least one antigenic epitope. An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (K D ) is ≦1 μM, preferably ≦100 nM, more preferably ≦10 nM, and most preferably ≦100 pM to about 1 pM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art.  
       [0161] 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.  
       [0162] Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). Some of these antibodies are discussed below.  
       [0163] Polyclonal Antibodies  
       [0164] 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).  
       [0165] 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).  
       [0166] Monoclonal Antibodies  
       [0167] 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.  
       [0168] 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.  
       [0169] 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 ANTLBODIES: 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.  
       [0170] Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, Calif. and the American Type Culture Collection, Manassas, Va. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).  
       [0171] The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). It is an objective, especially important in therapeutic applications of monoclonal antibodies, to identify antibodies having a high degree of specificity and a high binding affinity for the target antigen.  
       [0172] After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods (Goding, 1986). Suitable culture media for this purpose include, for example, Dulbecco&#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.  
       [0173] 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.  
       [0174] 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.  
       [0175] Humanized Antibodies  
       [0176] 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)).  
       [0177] Human Antibodies  
       [0178] Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed “human antibodies”, or “fully human antibodies” herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).  
       [0179] 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)).  
       [0180] 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.  
       [0181] 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.  
       [0182] 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.  
       [0183] 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.  
       [0184] Fab Fragments and Single Chain Antibodies  
       [0185] According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e.g., U.S. Pat. No. 4,946,778). In addition, methods can be adapted for the construction of Fab expression libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal 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.  
       [0186] Bispecific Antibodies  
       [0187] 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.  
       [0188] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published May 13, 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).  
       [0189] Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121:210 (1986).  
       [0190] 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.  
       [0191] 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.  
       [0192] 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.  
       [0193] Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al., J. Immunol. 148(5):1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab′ portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The “diabody” technology described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (V H ) connected to a light-chain variable domain (V L ) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the V H  and V L  domains of one fragment are forced to pair with the complementary V L  and V H  domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994).  
       [0194] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).  
       [0195] 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), FcγR11 (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).  
       [0196] Heteroconjugate Antibodies  
       [0197] 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.  
       [0198] Effector Function Engineering  
       [0199] 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).  
       [0200] Immunoconjugates  
       [0201] 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).  
       [0202] 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.  
       [0203] 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.  
       [0204] 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.  
       [0205] Immunoliposomes  
       [0206] The antibodies disclosed herein can also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Pat. No. 5,013,556.  
       [0207] Particularly useful liposomes can be generated by the reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol, and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab′ fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al., J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. A chemotherapeutic agent (such as Doxorubicin) is optionally contained within the liposome. See Gabizon et al., J. National Cancer Inst., 81(19): 1484 (1989).  
       [0208] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention  
       [0209] 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.  
       [0210] Antibodies directed against a NOVX protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of a NOVX protein (e.g., for use in measuring levels of the NOVX protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies specific to a NOVX protein, or derivative, fragment, analog or homolog thereof, that contain the antibody derived antigen binding domain, are utilized as pharmacologically active compounds (referred to hereinafter as “Therapeutics”).  
       [0211] An antibody specific for a NOVX protein of the invention (e.g., a monoclonal antibody or a polyclonal antibody) can be used to isolate a NOVX polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation. An antibody to a NOVX polypeptide can facilitate the purification of a natural NOVX antigen from cells, or of a recombinantly produced NOVX antigen expressed in host cells. Moreover, such an anti-NOVX antibody can be used to detect the antigenic NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic NOVX protein. Antibodies directed against a NOVX protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include  125 I,  131 I,  35 S , or  3 H.  
       [0212] Antibody Therapeutics Antibodies of the invention, including polyclonal, monoclonal, humanized and fully human antibodies, may used as therapeutic agents. Such agents will generally be employed to treat or prevent a disease or pathology in a subject. An antibody preparation, preferably one having high specificity and high affinity for its target antigen, is administered to the subject and will generally have an effect due to its binding with the target. Such an effect may be one of two kinds, depending on the specific nature of the interaction between the given antibody molecule and the target antigen in question. In the first instance, administration of the antibody may abrogate or inhibit the binding of the target with an endogenous ligand to which it naturally binds. In this case, the antibody binds to the target and masks a binding site of the naturally occurring ligand, wherein the ligand serves as an effector molecule. Thus the receptor mediates a signal transduction pathway for which ligand is responsible.  
       [0213] Alternatively, the effect may be one in which the antibody elicits a physiological result by virtue of binding to an effector binding site on the target molecule. In this case the target, a receptor having an endogenous ligand which may be absent or defective in the disease or pathology, binds the antibody as a surrogate effector ligand, initiating a receptor-based signal transduction event by the receptor.  
       [0214] A therapeutically effective amount of an antibody of the invention relates generally to the amount needed to achieve a therapeutic objective. As noted above, this may be a binding interaction between the antibody and its target antigen that, in certain cases, interferes with the functioning of the target, and in other cases, promotes a physiological response. The amount required to be administered will furthermore depend on the binding affinity of the antibody for its specific antigen, and will also depend on the rate at which an administered antibody is depleted from the free volume other subject to which it is administered. Common ranges for therapeutically effective dosing of an antibody or antibody fragment of the invention may be, by way of nonlimiting example, from about 0.1 mg/kg body weight to about 50 mg/kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week.  
       [0215] Pharmaceutical Compositions of Antibodies  
       [0216] Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington: The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa.: 1995; Drug Absorption Enhancement: Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.  
       [0217] If the antigenic protein is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are preferred. However, liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable-region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA, 90: 7889-7893 (1993). The formulation herein can also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition can comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent. Such molecules are suitably present in combination in amounts that are effective for the purpose intended.  
       [0218] The active ingredients can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions.  
       [0219] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.  
       [0220] Sustained-release preparations can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.  
       [0221] ELISA Assay  
       [0222] An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., F ab  or F (ab)2 ) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term “biological sample”, therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in “ELISA: Theory and Practice: Methods in Molecular Biology”, Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, N.J., 1995; “Immunoassay”, E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, Calif., 1996; and “Practice and Theory of Enzyme Immunoassays”, P. Tijssen, Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-an analyte protein antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.  
       [0223] NOVX Recombinant Expression Vectors and Host Cells  
       [0224] Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding a NOVX protein, or derivatives, fragments, analogs or homologs thereof. As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a “plasmid”, which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are referred to herein as “expression vectors”. In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. In the present specification, “plasmid” and “vector” can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.  
       [0225] The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably-linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).  
       [0226] 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.).  
       [0227] 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.  
       [0228] 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.  
       [0229] Examples of suitable inducible non-fusion  E. coli  expression vectors include pTrc (Amrann et al., (1988)  Gene  69:301-315) and pET 11d (Studier et al., GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).  
       [0230] 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.  
       [0231] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast  Saccharomyces cerivisae  include pYepSec1 (Baldari, et al., 1987 . EMBO J.  6: 229-234), pMFa (Kurjan and Herskowitz, 1982 . Cell  30: 933-943), pJRY88 (Schultz et al., 1987 . Gene  54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (In Vitrogen Corp, San Diego, Calif.).  
       [0232] 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). 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.  
       [0233] 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).  
       [0234] 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.  
       [0235] 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.  
       [0236] 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.  
       [0237] 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.  
       [0238] 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).  
       [0239] 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.  
       [0240] Transgenic NOVX Animals  
       [0241] 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 NQVX 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.  
       [0242] A transgenic animal of the invention can be created by introducing NOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g., by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human NOVX cDNA sequences, i.e., any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, 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.  
       [0243] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of a NOVX gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g., functionally disrupt, the NOVX gene. The NOVX gene can be a human gene (e.g., the cDNA of any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66), 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 66, 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).  
       [0244] 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.  
       [0245] 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.  
       [0246] 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.  
       [0247] 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 Go 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.  
       [0248] Pharmaceutical Compositions  
       [0249] 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.  
       [0250] A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.  
       [0251] 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.  
       [0252] Sterile injectable solutions can be prepared by incorporating the active compound (e.g., a NOVX protein or anti-NOVX antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.  
       [0253] 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.  
       [0254] 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.  
       [0255] 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.  
       [0256] 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.  
       [0257] 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.  
       [0258] 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.  
       [0259] 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.  
       [0260] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.  
       [0261] Screening and Detection Methods  
       [0262] 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 m-RNA (e.g., in a biological sample) or a genetic lesion in a NOVX gene, and to modulate NOVX activity, as described further, below. In addition, the NOVX proteins can be used to screen drugs or compounds that modulate the NOVX protein activity or expression as well as to treat disorders characterized by insufficient or excessive production of NOVX protein or production of NOVX protein forms that have decreased or aberrant activity compared to NOVX wild-type protein (e.g.; diabetes (regulates insulin release); obesity (binds and transport lipids); metabolic disturbances associated with obesity, the metabolic syndrome X as well as anorexia and wasting disorders associated with chronic diseases and various cancers, and infectious disease(possesses anti-microbial activity) and the various dyslipidemias. In addition, the anti-NOVX antibodies of the invention can be used to detect and isolate NOVX proteins and modulate NOVX activity. In yet a further aspect, the invention can be used in methods to influence appetite, absorption of nutrients and the disposition of metabolic substrates in both a positive and negative fashion.  
       [0263] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.  
       [0264] Screening Assays  
       [0265] 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.  
       [0266] In one embodiment, the invention provides assays for screening candidate or test compounds which bind to or modulate the activity of the membrane-bound form of a NOVX protein or polypeptide or biologically-active portion thereof. The test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the “one-bead one-compound” library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e.g., Lam, 1997 . Anticancer Drug Design  12: 145.  
       [0267] 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.  
       [0268] 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; Carrell, et al., 1994 . Angew. Chem. Int. Ed. Engl.  33: 2061; and Gallop, et al., 1994 . J. Med. Chem.  37: 1233.  
       [0269] Libraries of compounds may be presented in solution (e.g., Houghten, 1992 . Biotechniques  13: 412-421), or on beads (Lam, 1991 . Nature  354: 82-84), on chips (Fodor, 1993 . Nature  364: 555-556), bacteria (Ladner, U.S. Pat. No. 5,223,409), spores (Ladner, U.S. Pat. No. 5,233,409), plasmids (Cull, et al., 1992 . Proc. Natl. Acad. Sci. USA  89: 1865-1869) or on phage (Scott and Smith, 1990 . Science  249: 386-390; Devlin, 1990 . Science  249: 404-406; Cwirla, et al., 1990 . Proc. Natl. Acad. Sci. U.S.A.  87: 6378-6382; Felici, 1991 . J. Mol. Biol.  222: 301-310; Ladner, U.S. Pat. No. 5,233,409.).  
       [0270] In one embodiment, an assay is a cell-based assay in which a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface is contacted with a test compound and the ability of the test compound to bind to a NOVX protein determined. The cell, for example, can of mammalian origin or a yeast cell. Determining the ability of the test compound to bind to the NOVX protein can be accomplished, for example, by coupling the test compound with a radioisotope or enzymatic label such that binding of the test compound to the NOVX protein or biologically-active portion thereof can be determined by detecting the labeled compound in a complex. For example, test compounds can be labeled with  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 a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX protein or a biologically-active portion thereof as compared to the known compound.  
       [0271] In another embodiment, an assay is a cell-based assay comprising contacting a cell expressing a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX or a biologically-active portion thereof can be accomplished, for example, by determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule. As used herein, a “target molecule” is a molecule with which a NOVX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses a NOVX interacting protein, a molecule on the surface of a second cell, a molecule in the extracellular milieu, a molecule associated with the internal surface of a cell membrane or a cytoplasmic molecule. A NOVX target molecule can be a non-NOVX molecule or a NOVX protein or polypeptide of the invention. In one embodiment, a NOVX target molecule is a component of a signal transduction pathway that facilitates transduction of an extracellular signal (e.g. a signal generated by binding of a compound to a membrane-bound NOVX molecule) through the cell membrane and into the cell. The target, for example, can be a second intercellular protein that has catalytic activity or a protein that facilitates the association of downstream signaling molecules with NOVX.  
       [0272] Determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by one of the methods described above for determining direct binding. In one embodiment, determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i.e. intracellular Ca 2+ , diacylglycerol, IP 3 , etc.), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising a NOVX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g., luciferase), or detecting a cellular response, for example, cell survival, cellular differentiation, or cell proliferation.  
       [0273] In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting a NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to bind to the NOVX protein or biologically-active portion thereof. Binding of the test compound to the NOVX protein can be determined either directly or indirectly as described above. In one such embodiment, the assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX or biologically-active portion thereof as compared to the known compound.  
       [0274] In still another embodiment, an assay is a cell-free assay comprising contacting NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to modulate (e.g. stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX can be accomplished, for example, by determining the ability of the NOVX protein to bind to a NOVX target molecule by one of the methods described above for determining direct binding. In an alternative embodiment, determining the ability of the test compound to modulate the activity of NOVX protein can be accomplished by determining the ability of the NOVX protein further modulate a NOVX target molecule. For example, the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra.  
       [0275] In yet another embodiment, the cell-free assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the NOVX protein to preferentially bind to or modulate the activity of a NOVX target molecule.  
       [0276] The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether) n , N-dodecyl—N,N-dimethyl-3-ammonio-1-propane sulfonate, 3-(3-cholamidopropyl) dimethylamminiol-1-propane sulfonate (CHAPS), or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane sulfonate (CHAPSO).  
       [0277] 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.  
       [0278] 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.  
       [0279] In another embodiment, modulators of NOVX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of NOVX mRNA or protein in the cell is determined. The level of expression of NOVX mRNA or protein in the presence of the candidate compound is compared to the level of expression of NOVX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of NOVX mRNA or protein expression based upon this comparison. For example, when expression of NOVX mRNA or protein is greater (i.e., statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of NOVX mRNA or protein expression. Alternatively, when expression of NOVX mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of NOVX mRNA or protein expression. The level of NOVX mRNA or protein expression in the cells can be determined by methods described herein for detecting NOVX mRNA or protein.  
       [0280] In yet another aspect of the invention, the NOVX proteins can be used as “bait proteins” in a two-hybrid assay or three hybrid assay (see, e.g., U.S. Pat. No. 5,283,317; Zervos, et al., 1993 . Cell  72: 223-232; Madura, et al., 1993 . J. Biol. Chem.  268: 12046-12054; Bartel, et al., 1993 . Biotechniques  14: 920-924; Iwabuchi, et al., 1993 . Oncogene  8: 1693-1696; and Brent WO 94/10300), to identify other proteins that bind to or interact with NOVX (“NOVX-binding proteins” or “NOVX-bp”) and modulate NOVX activity. Such NOVX-binding proteins are also involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway.  
       [0281] The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for NOVX is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein (“prey” or “sample”) is fused to a gene that codes for the activation domain of the known transcription factor. If the “bait” and the “prey” proteins are able to interact, in vivo, forming a NOVX-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with NOVX.  
       [0282] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.  
       [0283] Detection Assays  
       [0284] 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.  
       [0285] Chromosome Mapping  
       [0286] Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the NOVX sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, 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.  
       [0287] 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.  
       [0288] Somatic cell hybrids are prepared by fusing somatic cells from different mammals (eg., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes. See, e.g., D&#39;Eustachio, et al., 1983 . Science  220: 919-924. Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with translocations and deletions.  
       [0289] 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.  
       [0290] 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).  
       [0291] 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.  
       [0292] Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. Such data are found, e.g., in McKusick, MENDELIAN INHERITANCE IN MAN, available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, e.g., Egeland, et al., 1987 . Nature,  325: 783-787.  
       [0293] 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.  
       [0294] Tissue Typing  
       [0295] 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).  
       [0296] 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.  
       [0297] 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).  
       [0298] Each of the sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers that each yield a noncoding amplified sequence of 100 bases. If coding sequences, such as those of SEQ ID NO:2n-1, wherein n is an integer between 1 and 66, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.  
       [0299] Predictive Medicine  
       [0300] The invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) purposes to thereby treat an individual prophylactically. Accordingly, one aspect of the invention relates to diagnostic assays for determining NOVX protein and/or nucleic acid expression as well as NOVX activity, in the context of a biological sample (e.g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with aberrant NOVX expression or activity. The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer&#39;s Disease, Parkinson&#39;s Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. For example, mutations in a NOVX gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with NOVX protein, nucleic acid expression, or biological activity.  
       [0301] 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.)  
       [0302] 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.  
       [0303] These and other agents are described in further detail in the following sections.  
       [0304] Diagnostic Assays  
       [0305] 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 66, 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.  
       [0306] An agent for detecting NOVX protein is an antibody capable of binding to NOVX protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab′) 2 ) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect NOVX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of NOVX mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of NOVX genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of NOVX protein include introducing into a subject a labeled anti-NOVX antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.  
       [0307] 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.  
       [0308] 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.  
       [0309] 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.  
       [0310] Prognostic Assays  
       [0311] 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.  
       [0312] 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).  
       [0313] The methods of the invention can also be used to detect genetic lesions in a NOVX gene, thereby determining if a subject with the lesioned gene is at risk for a disorder characterized by aberrant cell proliferation and/or differentiation. In various embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic lesion characterized by at least one of an alteration affecting the integrity of a gene encoding a NOVX-protein, or the misexpression of the NOVX gene. For example, such genetic lesions can be detected by ascertaining the existence of at least one of: (i) a deletion of one or more nucleotides from a NOVX gene; (ii) an addition of one or more nucleotides to a NOVX gene; (iii) a substitution of one or more nucleotides of a NOVX gene, (iv) a chromosomal rearrangement of a NOVX gene; (v) an alteration in the level of a messenger RNA transcript of a NOVX gene, (vi) aberrant modification of a NOVX gene, such as of the methylation pattern of the genomic DNA, (vii) the presence of a non-wild-type splicing pattern of a messenger RNA transcript of a NOVX gene, (viii) a non-wild-type level of a NOVX protein, (ix) allelic loss of a NOVX gene, and (x) inappropriate post-translational modification of a NOVX protein. As described herein, there are a large number of assay techniques known in the art which can be used for detecting lesions in a NOVX gene. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.  
       [0314] In certain embodiments, detection of the lesion involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran, et al., 1988 . Science  241: 1077-1080; and Nakazawa, et al., 1994 . Proc. Natl. Acad. Sci. USA  91: 360-364), the latter of which can be particularly useful for detecting point mutations in the NOVX-gene (see, Abravaya, et al., 1995 . Nucl. Acids Res.  23: 675-682). This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e.g., genomic, mRNA or both) from the cells of the sample, contacting the nucleic acid sample with one or more primers that specifically hybridize to a NOVX gene under conditions such that hybridization and amplification of the NOVX gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any of the techniques used for detecting mutations described herein.  
       [0315] 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.  
       [0316] In an alternative embodiment, mutations in a NOVX gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, e.g., U.S. Pat. No. 5,493,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.  
       [0317] 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.  
       [0318] 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).  
       [0319] 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.  
       [0320] In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called “DNA mismatch repair” enzymes) in defined systems for detecting and mapping point mutations in NOVX cDNAs obtained from samples of cells. For example, the mutY enzyme of  E. coli  cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches. See, e.g., Hsu, et al., 1994 . Carcinogenesis  15: 1657-1662. According to an exemplary embodiment, a probe based on a NOVX sequence, e.g., a wild-type NOVX sequence, is hybridized to a cDNA or other DNA product from a test cell(s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, e.g., U.S. Pat. No. 5,459,039.  
       [0321] 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.  
       [0322] 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.  
       [0323] 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.  
       [0324] 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.  
       [0325] The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid or antibody reagent described herein, which may be conveniently used, e.g., in clinical settings to diagnose patients exhibiting symptoms or family history of a disease or illness involving a NOVX gene.  
       [0326] 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.  
       [0327] Pharmacogenomics  
       [0328] Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e.g., NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.  
       [0329] 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.  
       [0330] 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.  
       [0331] As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymorphisms of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and cytochrome pregnancy zone protein precursor enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite morphine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.  
       [0332] 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 a NOVX modulator, such as a modulator identified by one of the exemplary screening assays described herein.  
       [0333] Monitoring of Effects During Clinical Trials  
       [0334] 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.  
       [0335] 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.  
       [0336] In one embodiment, the invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e.g., an agonist, antagonist, protein, peptide, peptidomimetic, nucleic acid, small molecule, or other drug candidate identified by the screening assays described herein) comprising the steps of (i) obtaining a pre-administration sample from a subject prior to administration of the agent; (ii) detecting the level of expression of a NOVX protein, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the pre-administration sample with the NOVX protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of NOVX to higher levels than detected, i.e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of NOVX to lower levels than detected, i.e., to decrease the effectiveness of the agent.  
       [0337] Methods of Treatment  
       [0338] The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant NOVX expression or activity. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.  
       [0339] These methods of treatment will be discussed more fully, below.  
       [0340] Diseases and Disorders  
       [0341] 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.  
       [0342] 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.  
       [0343] 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).  
       [0344] Prophylactic Methods  
       [0345] In one aspect, the invention provides a method for preventing, in a subject, a disease or condition associated with an aberrant NOVX expression or activity, by administering to the subject an agent that modulates NOVX expression or at least one NOVX activity. Subjects at risk for a disease that is caused or contributed to by aberrant NOVX expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of the NOVX aberrancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression. Depending upon the type of NOVX aberrancy, for example, a NOVX agonist or NOVX antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein. The prophylactic methods of the invention are further discussed in the following subsections.  
       [0346] Therapeutic Methods  
       [0347] Another aspect of the invention pertains to methods of modulating NOVX expression or activity for therapeutic purposes. The modulatory method of the invention involves contacting a cell with an agent that modulates one or more of the activities of NOVX protein activity associated with the cell. An agent that modulates NOVX protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring cognate ligand of a NOVX protein, a peptide, a NOVX peptidomimetic, or other small molecule. In one embodiment, the agent stimulates one or more NOVX protein activity. Examples of such stimulatory agents include active NOVX protein and a nucleic acid molecule encoding NOVX that has been introduced into the cell. In another embodiment, the agent inhibits one or more NOVX protein activity. Examples of such inhibitory agents include antisense NOVX nucleic acid molecules and anti-NOVX antibodies. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e.g., by administering the agent to a subject). As such, the invention provides methods of treating an individual afflicted with a disease or disorder characterized by aberrant expression or activity of a NOVX protein or nucleic acid molecule. In one embodiment, the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e.g., up-regulates or down-regulates) NOVX expression or activity. In another embodiment, the method involves administering a NOVX protein or nucleic acid molecule as therapy to compensate for reduced or aberrant NOVX expression or activity.  
       [0348] 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).  
       [0349] Determination of the Biological Effect of the Therapeutic  
       [0350] 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.  
       [0351] 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.  
       [0352] Prophylactic and Therapeutic Uses of the Compositions of the Invention  
       [0353] The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.  
       [0354] As an example, a cDNA encoding the NOVX protein of the invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof. By way of non-limiting example, the compositions of the invention will have efficacy for treatment of patients suffering from diseases, disorders, conditions and the like, including but not limited to those listed herein.  
       [0355] 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 imiunospecifically-bind to the novel substances of the invention for use in therapeutic or diagnostic methods.  
       [0356] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. 
     
    
    
     EXAMPLES  
     Example A  
     Polynucleotide and Polypeptide Sequences, and Homology Data  
     Example 1.  
     [0357] 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   3840 bp                     NOV1a,     GCGCCGCGGCCGGCGATGAGCGCGAGGAGCCGGC   ATG AGCGCAGACAGCAGCCCTCTCGTGGGCAG       CG108945-01       DNA Sequence   CACGCCCACCGGTTATGGGACCCTGACGATAGGGACATCAATAGATCCCCTCAGCTCCTCAGTTTC                   ATCCGTCAGGCTCAGCGGCTACTGTGCAGTCCATGGAGAATCATCAACTATCACGTCGTAATCTG                   GATGATGGCTGGGATCCCTTTGCTGCTCTTCCGTTAAAAGCCCCTGTGGAAGGTGCGCCTGCGGCT                   CCGGCCCTGCAACCTGGCCCACGCCGAAACACTCGTTATCGAAATAAGAGACAAAGAGGATAGTTC                   CTGGCAGCTCTTCACTGTCCAGGTGCAGACTGAGGCCATCAACGGGAACAGCCTGGAGCCGTCCCC                   ACAGTCCCAGGCAGAGGATGGCCGGAGCCAGGCGGCAGTTGGGGCGGTACCAGAGGGTGCCTGGAA                   GATACGGGCCCAGCTCCACAAGAGCGAGGAGGCCGTGAGTGTCAAACAGAAGCGAATGCTGCAATA                   TTACCTCTTCCAGGGCCAGCGCTATATCTAAATCGAGACCCAGCAAGCCTTCTACCAAATCAGCCT                   CTAAACCATAACCGCTCTTAATGACGACGTCCACCGCTCCCGCCATAACCTCAGCCTCCAAAACCA                   AATGGTGAGGAAGGCCATTTACGGCCCCAACGTGATCAGCATACCGGTCAAGTCCTACCCCCAGCT                   GCTGGTGGACGACGCACTGAACCCCTACTATGCGTTCCAGGCCTTCAGCATCGCGCTGTGGCTGGC                   TGACCACTACTACTGGTACGCCCTGTCCATCTTCCTCATTTCCTCCATCTCCATCTCCCTGTCGCT                   GTACAAGACCAGAAAGCAAAGCCAGACTCTAAGGGACATGGTCAAGTTGTCCATGCGGGTGTGCGT                   GTGCCGGCCAGGGGGAAAAGACAGAGTGGTGGACTCCAGTGAGCTAGTGCCCGGAGACTGCCTAAT                   GCTGCCCCAGGAGGGTGGGCTGATGCCCTGTGATGCCGCCCTGGTGGCCGGCGAGTGCATGGTGAA                   CTGAGAGCTCTCTGACAGGAGAAAAGCATTCCAGTGCTGAAGACGGCACTGCCAAAGAACTGGGCC                   CTACTGTGCAAAGACACACCGGCGGCACACACTCTTCTCCGGGACCCTCATCTTGCAGGCCCGGGC                   CTATGTGGGAGGCAACGCACGTCCTGGCAGTGGTGACCCGCACAGGGTTCTGCACGGCGGAAGCCT                   GGTGAGCTCCATCTTGCACCCCCGGCCCATCAACTTCAAGTTCTATAAACACAGCATGAAGTTTGT                   GGCTGCCCTCTCTGTCCTGGGCTCTCCTCGGCACCATCTACAGCATCTTCATCCTCTACCGAACCG                   GGTGCCTCTGAATGAGATTGTAATCCGGGCTCTCGACCTGGTGACCGTGGTGGTGCCACCTGCCCT                   GCCTGCTGCCATGACTGTGTGCACGCTCTACGCCCAGAGCCGACTGCGGAGACAGGGCATTTTCTG                   CATCCACCCACTGCGCATCAACCTGGGGGGCAAGCTGCAGCTGGTGTGTTTCGACAAGACGGGCAC                   CCTCACTGAGGACGGCTTAGACGTGATGGGGGTGGTGCCCCTGAAGGGGCAGGCATTCCTGCCCCT                   GGTCCCAGAGCCTCGCCGCCTGCCTGTGGCGCCCCTCCTCCGAGCACTGGCCACCTGCCATGCCCT                   CAGCCGGCTCCAGGACACCCCCGTGGGCGACCCCATGGACTTGAAGATGGTGGAGTCTACTGGCTG                   GGTCCTGGAGGAAGAGCCGGCTGCAGACTCAGCATTTGGGACCCAGGTCTTGGCAGTGATGAGACC                   CCCACTTTCGGAGCCCCAGCTGCAGGCAATGCACGAGCCCCCGGTGCCAGTCAGCGTCCTCCACCG                   CTTCCCCTTCTCTTCGGCTCTGCAGCGCATGAGTGTGGTGGTAACGTAACCAGAAGCCACTAAGCC                   CGAGGCCTACGTCAAAGGCTCCCCGGAGCTGGTGGCAGGGCTCTGCAACCCCGAGACAGTGCCCAC                   CGACTTCGCCCAGATGCTGCAGAGCTATACAGCTGCTAACTACCGTGTCGTAACCCTAACCAGCAA                   CGCCACTGCCCACTGTGCCCAGCCTGGAGGCAGCCCGCAACTGACGAGGGACACTGTGGAAGGAGA                   CCTGAGCCTCCTGGGGCTGCTCGTCATGAGGAACCTACTGAAGCCGCAGACAACGCCAGTTATCCA                   GGCTCTGCGAAGGACCCGCATCCGCGCCGTCATGGTGACAGGGGACAACCTGCAGACAGCAATGAC                   TGTGGCCCCGGGCTGTGGCATGGTGGCCCCCCAGGAGCATCTGATCATCGTCCACGCCACCCACCC                   TGAGCGGGGTCAGCCTGCCTCTCTCGAGTTCCTGCCGATGGAGTCCCCCACAGCCGTGAATGGCGT                   TAAGGATCCTGACCAAACTGCAAGCTACACCGTGGAGCCAGACCCCCGATCAGAACACCTAACCCT                   CAGCGGGCCCACCTTTGGTATCATTGTGAAGCACTTCCCCAAGCTGCTGCCCAAGGTCCTGGTCCA                   GGGCACTGTCTTTGCCCGCATGGCCCCTGAGCAGAAGACAGAGCTGGTGTGCGAGCTACAGAAGCT                   TCAGTACTGGCGTGGGGCATGTGCGGAGACGGCGCCAATGACTGTGAAGCCCTGAACAACTGATGT                   GGCATCTCGGCTGTCCCAGGCAGAAGCCTCAGTGGTCTCACCCTTCACCTCGAGCATGGCCAGTAT                   TGAGTCCGTGCCCATGGTCATCAGGCACGGGCGCTGTTCCCTTGACACTTCGTTCAGCCTCTTCAA                   GTACATGGCTCTGTACAGCCTGACCCAGTTCATCTCCGTCCTGATCCTCTACACGATCAACACCAA                   CCTGGGTGACCTGCAGTTCCTGGCCATCGACCTGGTCATCACCACCACAGTGGCAGTGCTCATGAG                   CGAGAAGGCGCCAGCGCTGGTCCTGGGACGGCTGCGGCCACCGGGGGCGCTGCTCAGCGTGCCCGT                   GCTCAGCAGCCTGCTGCTGCAGATCGTCCTGGTGACCGGCGTGCAGCTACGGGGCTACTTCCTGAC                   GCTGGGCCCAGCCATGTTCGTGCCTCTGAACAGGACAGTGGCCGCACCAGACAACCTGCCCAACTA                   CAAGAACACCGTGGTCTTCTCTCTGTCCAGCTTCCAGTACCTCATCCTGGCTGCACCCGTGTCCAA                   GGGGGCGCCCTTCCGCCGGCCGCTCTACACCAATGTGCCCTTCCTGGTGGCCCTGGCGCTCCTGAG                   CTCCGTCCTGGTGGGCCTTGTCCTGGTCCCCGGCCTCCTGCAGGGGCCGCTGGCGCTGAGGAACAT                   CACTGACACCGGCTTCAAGCTGCTGCTGCTGGGTCTGGTCACCCTCAACTTCGTGGGAACCTTCAT                   GCTGGAGAGCGTGCTAGACCAGTGCCTCCCCGCCTCCCTGCGCCGCCTCCGGCCCAAGCGAACCTC                   CAAGAAGCGCTTCAAGCAGCTGGAACGAGAGCTGGCCGAGCAGCCCTGGCCGCCGCTGCCCGCCGG                   CCCCCCTGAGG TAG   TGCAGCCCACAAGCACCCCAGACACTGGAACTCCCTGCCTCTGAGCAACCAA                       CTGGACCCCTCTCCAGCAACACCACCGCCACCACCTCCCACATCCCTGAGGTTGGCGACTGTCTAC                       ACTCCTCCCCCGAGACCACCCCCACCCTGGGGAAGCGTTGACTACTGTCCCCTACCTTGGACCATC                       CCGCGTAGGGGTGGCAGCCCCCAGCTCCCCTCAGTGCTGCTGTCAGTGTAGCAAATAAAGTCATGA                       TATTTTCCTGGC                                           ORF Start: ATG at 35       ORF Stop: TAG at 3575           SEQ ID NO:2   1180 aa   MW at 128792.0 kD                     NOV1a,   MSADSSPLVGSTPTGYGTLTIGTSIDPLSSSVSSVRLSGYCGSPWRVIGYHVWMAAGIPLLLFR       CG108945-01       Protein Sequence   WKPLWGVRLRLRPCNLAHAETLVIEDKEDSSWQLFTVQVQTEAIGEGSLEPSPQSQAEDGRSQA                   AVGAVPEGAWKDTAQLHKSEEAVSVCQKRVLRYYLFQGQRYIWIETQQAFYQVSLLDHGRSCDDAA                   RSRHGLSLQDQMVRKAIYGPNVISIPVKSYPQLLVDEALNPYYGFQAFSIALWLADHYYWYALCIF                   LISSISICLSLYKTRKQSQTLRDMVKLSMRVCVCRPGGEEEWVDSSELVPGDCLVLPQEAALMPCD                   AALVAGECMVNESSLTGESIPVLKTALPEGLGPYCAEThRRHTLFCGTLILQARAYVGPHVLAVVT                   RTGFCTAKGGLVSSILHPRPINFKFYKHSMKFVAALSVLALLGTIYSIFILYRNRVPLNEIVIRAL                   DLVTVVVPPALPAAMTVCTLYAQSRLRRQGICIHPLRIAALGGKLQLVCFDKTGTLTEDGLDVMGV                   VPLKGQAFLPLVPEPRRLPVGPLLRALATCHALSRLQDTPVGDPDLKMVESTGWVLEEEPAADASA                   FGTQVLAVMRPPLWEPQLQANEEPPVPVSVLHRFPFSSALQRMSVVVAWPGATQPEAAAKGSPELV                   AGLCNPETVPTDFAQMLQSYTAAGYRVVALASKPLPTVPSLEAAQQLTRDTVEGDLSLLGLLVMPN                   LLKPQTTPVIQALRRTRIRAVMVTGDNLQTAVTVARGCGMXIAPQEHLIIVIIATHRGQPASLEFL                   PMESPTAVNGVKDPDQAASYTVEPDPRSRHLALSGPTFGIIVKHFPKLLPKVLVQGTVFARMAPEQ                   KTELVCELQKLQYCVGMCGDGANDCCALKAADVGISLSQAEASVVSPFTSSMASIECVPMVIREGR                   CSLDTSFSVFKYMALYSLTQFISVLILYTINTNLGDLQFLAIDLVITTTVAVLMSRTGPALVLGRV                   RPPGALLSVPVLSSLLLQMVLVTGVQLGGYFLTLAQPWFVPLNRTVAAPDILPNYENTVVFSLSSF                   QYLILAAAVSKGAPFRRPLYTNVPFLVALALLSSVLVGLVLVPGLLQGPLALRNITDTGFKLLLLG                   LVTLNFVGAFMLESVLDQCLPACLRRLRPKRASKKRFKQLERELAEQPWPPLPAGPLR                                     SEQ ID NO:3   3540 bp                     NOV1b,     GCGCCGGGGCCGGCGATGAGCGCGAGGAGCCGGC   ATG AGCGCAGACAGCAGCCCTCTCGTGGGCAG       CG108945-02       DNA Sequence   CACGCCCACCGGTTATGGGACCCTGACGATAGGGACATCAATAGATCCCCTCAGCTCCTCAGTTTC                   ATCCGTGACGCTCAGCGGCTACTGTGGCAGTCCATGGAGGGTCATCGGCTATCACGTCGTGGTCTG                   GATGATGGCTGGGATCCCTTTGCTGCTCTTCCGTTGGAAGCCCCTGTGGGGGGTGCGGCTGCGGCT                   CCGGCCCTGCAACCTGGCCCACGCCGAAACACTCGTTATCGAAATAAGAGACAAAGACGATAGTTC                   CTGGCAGCTCTTCACTGTCCAGGTGCAGACTGAGGCCATCGGCGAGGGCAGCCTGGAGCCGTCCCC                   ACAGTCCCACGCAGAGGATGGCCGGAGCCAGGCGGCAGTTGGGGCGGTACCAGAGGGTGCCTGGAA                   GGATACGGCCCAGCTCCACAAGAGCGAGGAGGCGGTGAGTGTCGGACAGAAGCGGGTGCTGCGGTA                   TTACCTCTTCCAGGGCCAGCGCTATATCTGGATCGAGACCCAGCAAGCCTTCTACCAGGTCAGCCT                   CCTGGACCATGGCCGCTCTTGTGACGACGTCCACCGCTCCCGCCATGGCCTCAGCCTCCAGGACCA                   AATGGTGAGGAAGGCCATTTACGGCCCCAACGTGATCAGCATACCGGTCAAGTCCTACCCCCAGCT                   GCTGGTGGACGAGGCACTGAACCCCTACTATGGGTTCCAGGCCTTCAGCATCGCGCTGTGGCTGGC                   TGACCACTACTACTGGTACGCCCTGTGCATCTTCCTCATTTCCTCCATCTCCATCTGCCTGTCGCT                   GTACAAGACCAGAAAGCAAAGCCAGACTCTAAGGGACATGGTCAAGTTGTCCATGCGGGTGTGCGT                   GTGCCGGCCAGGGGGAGAGGAAGAGTGGGTGGACTCCAGTGAGCTAGTGCCCGGAGACTGCCTGGT                   GCTGCCCCAGGAGGGTGGGCTGATGCCCTGTGATGCCGCCCTGGTGGCCCGCGAGTGCATGGTGAA                   TGAGAGCTCTCTGACAGGAGAGAGCATTCCAGTGCTGAAGACGGCACTGCCGGAGGGGCTGGGGCC                   TACTGTGCAGAGACACACCGGCGGCACACACTCTTCTGCGGGACCCTCATCTTGGCAGGCCCGGGC                   TATGTGGGACCGCACGTCCTGGCAGTGGTGACCCGCACAGGGTTCTGGCACGGCAAAAGGGGCCCT                   GGTGAGCTCCATCTTGCACCCCCGGCCCATCAACTTCAAGGTTCTATAACACAGCATGAAGTTTGT                   GGCTGCCCTCTCTGTCCTGGCTCTCCTCGGCACCATCTACAGCATCTTCATCCTCTACCGAAACCG                   GGTGCCTCTGAATGAGATTGTAATCCGGGCTCTCGACCTGGTGACCGTGGTGGTGCCACCTGCCCT                   GCCTGCTGCCATGACTGTGTGCACGCTCTACCCCCAGAGCCGACTGCGGAGACAGGGCATTTTCTG                   CATCCACCCACTGCGCATCAACCTGGGGGGCAAGCTGCAGCTGGTGTGTTTCGACAAGACGGGCAC                   CCTCACTGAGGACGGCTTAGACGTGATGGGGGTGGTGCCCCTGAAGGGGCAGGCATTCCTGCCCCT                   GGTCCCAGAGCCTCGCCGCCTGCCTGTGCGGCCCCTGCTCCGAGCACTGGCCACCTGCCATGCCCT                   ACAACCGGCTCCAGGACACCCCCGTGGGCGACCCCATGGACTTGAGATGGTGGAGTCTACTGGCTG                   GGTCCTGGAGGAAGAGCCGGCTGCAGACTCAGCATTTGGGACCCAGGTCTTGGCAGTGATGAGACC                   CCACTTTGGGAGCCCCAGCTGCACCGGAATGGAGGAGCCCCCGGTGCCAGTCAGCGTCCTCCACCG                   CTTCCCCTTCTCTTCGGCTCTGCAGCGCATGACTGTGGTGGTGGCGTGGCCAGCGGCCACTCAGCC                   CGAGGCCTACGTCAAAGGCTCCCCGGAGCTGGTCGCAGCGCTCTGCAACCCCGAGACAGTGCCCAC                   CGACTTCGCCCAGATGCTGCAGAGCTATACAGCTGCTGGCTACCGTGTCGTGGCCCTGGCCAGCAA                   GCCACTGCCCACTGTGCCCAGCCTGGAGGCAGCCCAGCAACTGACGAGGGACACTGTGGAAGGAGA                   CCTGAGCCTCCTGGGGCTGCTGGTCATGAGGAACCTACTGAAGCCGCACACAACGCCAGTTATCCA                   GGCTCTGCGAAGGACCCGCATCCGCGCCGTCATCGTGACAGGGGACAACCTGCAGACAGCGGTGAC                   TGTGGCCCGGGGCTGTCGCATCGTGGCCCCCCAGGAGCATCTGATCATCGTCCACGCCACCCACCC                   TGAGCGGGGTCAGCCTGCCTCTCTCGAGTTCCTGCCGATGGAGTCCCCCACAGCCGTGAATGGCGT                   TAAGGTCCTCGTCCAGGGCACTGTCTTTGCCCGCATGGCCCCTGAGCAGAAGACAGAGCTGGTGTG                   CGAGCTACAGAAGCTTCAGTACTGCGTGGGCATGTGCGGAGACGGTGCCAATGACTGTGGGGCCCT                   GAAGGCGGCTGATGTCGGCATCTCGCTGTCCCAGGCAGAAGCCTCAGTGGTCTCACCCTTCACCTC                   GAGCATGGCCAGTATTGAGTGCGTGCCCATGGTCATCAGGGAGGGGCGCTGTTCCCTTGACACTTC                   GTTCAGCGTCTTCAAGTACATGGCTCTGTACAGCCTGACCCAGTTCATCTCCGTCCTGATCCTCTA                   CACGATCAACACCAACCTGGGTGACCTGCAGTTCCTGGCCATCGACCTGGTCATCACCACCACAGT                   GGCAGTGCTCATCAGCCCCACGGGGCCAGCGCTGGTCCTCGGACCGGTGCGGCCACCCGGGGCGCT                   GCTCAGCGTGCCCGTGCTCAGCAGCCTGCTGCTGCAGATCGTCCTGGTGACCGGCGTGCAGCTAGG                   GGGCTACTTCCTGACCCTGGCCCACCCATGGTTCGTGCCTCTGAACAGGACAGTGGCCGCACCAGA                   CAACCTGCCCAACTACGAGAACACCGTGGTCTTCTCTCTGTCCAGCTTCCAGTACCTCATCCTGGC                   TGCAGCCGTGTCCAAGGGGGCGCCCTTCCGCCGGCCGCTCTACACCAATGAGCGTGCTAGACCAGT                   CCCTCCCCGCCTGCCTGCGCCGCCTCCGGCCCAAGCGGGCCTCCAAGAAGCGCTTCAAGCAGCTGG                   AACGAGAGCTGGCCGAGCAGCCCTGGCCGCCGCTGCCCGCCGGCCCCCTGAGGTAGTGCAGGCCCA                   CGGGCACCCCAGACACTGGAACTCCCTGCCTCTGAGCCACCAACTGGACCCCTCTCCAGCAACACC                   ACCGCCACCACCTCCCACATCCCTGAGGTTGGCGACTGTCTACACTCCTCCCCCGAGACCACCCCC                   ACCCTGGGGAAGCGTTGACTACTGTCCCCTACCTTGGACCATCCCGCGTAGGGGTGGCAGCCCCCA                   GCTCCCCTCAGTGCTGCTGTCAGTG TAG   CAAATAAAGTCATG                                           ORF Start: ATG at 35       ORF Stop:TAG at 3524           SEQ ID NO:4   1163 aa   MW at 126445.6 kD                     NOV1b,   MSADSSPLVGSTPTGYGTLTIGTSIDPLSSSVSSVRLSGYCGSPWRVIGYHVVVWMMAGIPLLLFR       CG108945-02       Protein Sequence   WKPLWOVRLRLRPCNLAHAETLVIEIRDKEDSSWQLFTVQVQTEAIGEGSLAAPSPQSAEDGRSQA                   AVGAVPEGAWKDTAQLHKSEEAVSVGQKRVLRYYLFQGQRYIWIETQQAFYQVSLLDHGRSCDDVH                   RSRHGLSLQDQMVRKAIYGPNVISIPVKSYPQLLVDEALNPYYGFQAFSIALWLADEYYWYALCIF                   LISSISICLSLYKTRKQSQTLRDMVKLSMRVCVCRPGGEEEWVDSSELVPGDCLVLPQEGGLMPCD                   AALVAGECMVNESSLTGESIPVLKTALPEGLGPYCAETIHRRIHTLFCGTLILQAYVGPHVLAVVT                   RTGFCTAKGGLVSSILHPRPINFKFYKHSMKFVAALSVLALLGTIYSIFILRYYRVPLNEIVIRAL                   DLVTVVVPPALPAAMTVCTLYAQSRLRRQGIFCIHPLRINLGGKLQLVCFDKTGTLTEDGLDVMGV                   VPLKGQAFLPLVPEPRRLPVGPLLRALATCHALSRLQDTPVGDPMDLKNVESTGWVLEEEPAADSA                   FGTQVLAVMRPPLWEPQLQAMEEPPVPVSVLHRFPFSSALQRMSVVVAWPGATQPEAYVKGSPELV                   AGLCNPETVPTDFAQMLQSYTAAGYRVVALASKPLPTVPSLEAAQQLTRDTVEGDLSLLGLLVMRN                   LLKPQTTPVIQALRRTRIRAVMVTGDNLQTAVTVARGCGMVAPQEHLIIVHATHPERGQPASLEFL                   PMESPTAVUGVKVLVQGTVFAAMAPEQKTELVCELQKLQYCVGMCGDGANACGALKAADVGISLSQ                   AEASVVSPFTSSMASIECVPMVIREGRCSLDTSFSVFKYMALYSLTQFISVLILYTINTNLGDLQF                   LAIDLVITTTVAVLMSRTGPLVLGRVRPPGALLSVPVLSSLLLQMVLVTGVQLGGYFFLTLAQPWF                   VPLNRTVAAPDMLPNYENTVVFSLSSFQYLILAAAVSKQAPFRRPLYTNERARPVPPRLPAPPPAQ                   AGLQEALQAAGTRAGRAALAAAARRPPEVVQAHGHPRHWNSLPLSHQLDPSPATPPPPPPTSLRLA                   TVYTPPPRPPPPWGSVDYCPLPWTIPRRGGSPQLPSVLLSV                  
 
     [0358] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 1B.  
               TABLE 1B                          Comparison of NOV1a against NOV1b.                                     NOV1a   Identities/               Residues/   Similarities           Protein   Match   for the           Sequence   Residues   Matched Region                       NOV1b   1 . . . 1078   1039/1078 (96%)               1 . . . 1039   1039/1078 (96%)                      
 
     [0359] Further analysis of the NOV1a protein yielded the following properties shown in Table 1C.  
               TABLE 1C                       Protein Sequence Properties NOV1a                                        SignalP   Cleavage site between residues 12 and 13       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 4; pos. chg 0; neg. chg 1           H-region: length 21; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −7.09           possible cleavage site: between 31 and 32           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 10                                         INTEGRAL   Likelihood =   −2.28   Transmembrane   47-63           INTEGRAL   Likelihood =   −6.05   Transmembrane   259-275           INTEGRAL   Likelihood =   −6.48   Transmembrane   431-447           INTEGRAL   Likelihood =   −3.29   Transmembrane   457-473           INTEGRAL   Likelihood =   −0.80   Transmembrane   938-954           INTEGRAL   Likelihood =   −4.25   Transmembrane   963-979           INTEGRAL   Likelihood =   −5.79   Transmembrane    996-1012           INTEGRAL   Likelihood =   −2.87   Transmembrane   1049-1065           INTEGRAL   Likelihood =   −11.83   Transmembrane   1082-1098           INTEGRAL   Likelihood =   −6.58   Transmembrane   1118-1134           PERIPHERAL   Likelihood =   1.75   (at 379)                         ALOM score: −11.83 (number of TMSs: 10)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 54           Charge difference: 3.5 C(5.0)-N(1.5)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt; membrane topology: type 3b           MITDISC: discrimination of mitochondrial targeting seq                                         R content:   0   Hyd Moment (75):   5.53               Hyd Moment (95):   4.13   G content:   4           D/E content:   2   S/T content:   10                         Score: −6.25           Gavel: prediction of cleavage sites for mitochondrial preseq           R-2 motif at 88 LRP|CN           NUCDISC: discrimination of nuclear localization signals           pat4: RPKR (4) at 1150           pat7: none           bipartite: none           content of basic residues: 8.6%           NLS Score: −0.22           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           66.7%: endoplasmic reticulum           11.1%: mitochondrial           11.1%: vesicles of secretory system           11.1%: vacuolar           &gt;&gt; prediction for CG108945-01 is end (k = 9)                  
 
     [0360] 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 1D.  
               TABLE 1D                          Geneseq Results for NOV1a                                         NOV1a   Identities/                   Residues/   Similarities       Geneseq   Protein/Organism/Length   Match   for the   Expect       Identifier   [Patent #, Date]   Residues   Matched Region   Value                                         AAU91183   Human HEAT-1 polypeptide -   1 . . . 1180   1180/1180 (100%)    0.0             Homo sapiens , 1180 aa.   1 . . . 1180   1180/1180 (100%)            [WO200216591-A2, 28 FEB. 2002]       AAM93906   Human polypeptide, SEQ ID NO:   339 . . . 1180    841/842 (99%)   0.0           4053 -  Homo sapiens , 842 aa.   1 . . . 842    841/842 (99%)           [EP1130094-A2, 05 SEP. 2001]       AAM79751   Human protein SEQ ID NO 3397 -   515 . . . 1180    633/666 (95%)   0.0             Homo sapiens , 666 aa.   1 . . . 666    637/666 (95%)           [WO200157190-A2,           09 AUG. 2001]       ABB11769   Human dJ37C10.3 ATPase   515 . . . 1180    633/666 (95%)   0.0           homologue, SEQ ID NO: 2139 -   1 . . . 666    637/666 (95%)             Homo sapiens , 666 aa.           [WO200157188-A2,           09 AUG. 2001]       AAM78767   Human protein SEQ ID NO 1429 -   603 . . . 1078     476/476 (100%)   0.0             Homo sapiens , 600 aa.   1 . . . 476     476/476 (100%)           [WO200157190-A2,           09 AUG. 2001]                  
 
     [0361] In a BLAST search of public sequence databases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1E.  
               TABLE 1E                          Public BLASTP Results for NOV1a                                         NOV1a   Identities/           Protein       Residues/   Similarities       Accession       Match   for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value                                         Q9NQ11   Probable cation-transporting   1 . . . 1180    1180/1180 (100%)   0.0           ATPase 1 (EC 3.6.1.-) -  Homo     1 . . . 1180    1180/1180 (100%)             sapiens  (Human), 1180 aa.       Q8N4D4   Putative ATPase -  Homo sapiens     93 . . . 1180     1088/1088 (100%)   0.0           (Human), 1088 aa (fragment).   1 . . . 1088    1088/1088 (100%)       AAH30267   Similar to putative ATPase -   1 . . . 1078   1033/1078 (95%)   0.0             Homo sapiens  (Human), 1158 aa.   1 . . . 1034   1034/1078 (95%)       Q8NBS1   Hypothetical protein FLJ90829 -   339 . . . 1180     841/842 (99%)   0.0             Homo sapiens  (Human), 842 aa.   1 . . . 842     841/842 (99%)       AAH23746   Similar to putative ATPase -  Mus     9 . . . 613     520/605 (85%)   0.0             musculus  (Mouse), 650 aa.   1 . . . 600     550/605 (89%)                  
 
     [0362] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1F.  
               TABLE 1F                          Domain Analysis of NOV1a                                     Identities/                   Similarities           NOV1a Match   for the   Expect       Pfam Domain   Region   Matched Region   Value               E1-E2_ATPase   299 . . . 387   33/94 (35%)   1.4e-14               74/94 (79%)       Hydrolase   507 . . . 899   45/399 (11%)    0.00041               224/399 (56%)                   
 
     Example 2.  
     [0363] The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.  
               TABLE 2A                       NOV2 Sequence Analysis                                                SEQ ID NO:5   728 bp                     NOV2a,     CTTCCAACTCGCCCCGCTCGGTCACCCGCAGCAAGGCGTGCAGTTTCCCAACTCTCTGCGCAACCG         CG112559-03       DNA Sequence     GGGAAGGTCAGCGCCGTA   ATG GCGTTCTTCGCGTCGGGACCCTACCTGACCCATCAGCAAAAGGTG                   TTGCGGCTTTATAAGCGGGCGCTACGCCACCTCGAGTCGTGGTGCGTCCAGAGAGACAAATACCGA                   TACTTTGCTTGTTTGATGAGAGCCCGGTTTGAAGAACATAAGAATGAAAAGGATATAACGAAGGCC                   ACCCAGCTGCTGAAGGAGGCCGAGGAAGAATTCTGGTACCGTCAGCATCCACAGCCATACATCTTC                   CCTGACTCTCCTGGGGGCACCTCCTATGAGAGATACGATTGCTACAAGGTCCCAGAATGGTGCTTA                   CCGATGACTGCATCCTTCTGAGAAGGcATGTATCCTGATTACTTTGCCAAGAGAGAACAGTGGAAG                   AAACTGCGGAGGGAAAGCTGGGAACGAGAGGTTAAGCAGCTGCAGGAGGAAACGCCACCTGGTGGT                   CTTTAACTGAAGCTTTGCCCCCTGCCCGAAAGGAAGGTGATTTGCCCCCACTGTGGTGGGGATATT                   GTGACCAGACCCCGGGAGGCGGCCCATG TAG   AAGAGAGAGACCTCATCTTTAATGCTTGCAAGTGA                       AATATGTTACAGAACATGCACTTGCCCTAATAAAAAAATCAGTGAAATGGTCAAAAAAAAAAAAAA                       AA                                           ORF Start: ATG at 85       ORF Stop: TAG at 622           SEQ ID NO:6   179 aa   MW at 21830.7 kD                     NOV2a,   MAFLASGPYLTHQQKVLRLYKRALRHLESWCVQRDKYRYFACLMPARFEEHKNEKDMAKATQLLKE       CG112559-03       Protein Sequence   AEEEFWYRQHLPQPYIPDSPGGTSYERYDCYRVPEWCLDDWHPSEKAMYPDYFAKREQWKKLRRES                   WEREVKQLQEETPPGGPLTEALPPARKEGDLPPLWWYIVTRPRERPM                   SEQ ID NO:7   510 bp       NOV2b,     GGCAGAGCCCCGCTCAGTCACCCGCAGCAGGCGTGCAGTTTCCCGGCTCTCCGCGCGGCCGGGGAA         CG112559-03       Protein Sequence     GGTCAGCGCCGTA   ATG GCGTTCTTGGCGTCGGGACCCTACCTGACCCATCACCAAAAGGTGTTGCG                   GCTTTATAAGCGGGCGCTACGCCACCTCGAGTCGTGGTGCGTCCAGAGAGACAAATACCGATACTT                   TGCTTGTTTGATGAGAGCCCGGTTTGAAGAAACTGCGGAGGGAAAGCTCGGAACGAGAGGT TAA   GC                       AGCTGCAGGAGGAAACGCCACCTGGTGGTCCTTTAACTGAAGCTTTCCCCCCTGCCCGAAAGGAAG                       GTGATTTGCCCCCACTGTGGTGGTATATTGTGACCAGACCCCGGGAGCGGCCCATGTAGAAAGAGA                       GAGACCTCATCTTTCATGCTTGCAAGTGAAATATGTTACAGAACATGCACTTGCCCTAATAAAAAA                       TCAGTGAAATGGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA                                           ORF Start: ATG at 80       ORF Stop: TAA at 260           SEQ ID NO:8   60 aa   MW at 7152.3 kD                     NOV2b,   MAFLASGPYLTHQQKVLPWYKRALRHLESWCVQRDKYRYFACLMRARFEETAEGKLGTRG       CG1125 59-02       Protein Sequence                                     SEQ ID NO:9   728 bp                     NOV2c,     CTTCCGGCTGGCCCCGCTCGGTCACCCGCAGCAGGCGTGCAGTTTCCCGGCTCTCTGCGCGGCCG         CG112559-01       DNA Sequence     GGGAAGGTCAGCGCCGTA   ATG GCGTTCTTGGCGTCGGGACCCTACCTGACCCATCAGCAAAAGGTG                   TTGCGGCTTTATAAGCGGGCGCTACGCCACCTCGAGTCGTGGTGCGTCCAGAGAGACAAATACCGA                   TACTTTGCTTGTTTGATGAGAGCCCGGTTTGAAGAACATAAGAATGAAAAGGATATGGCGAAGGCC                   ACCCAGCTGCTGAAGGAGGCCGAGGAAGAATTCTGGTACCGTCAGCATCCACAGCCATACATCTTC                   CCTGACTCTCCTGGGGCACCTCCTATGAGAGATACGATTGCTACAAGAATCCCAGAATAATGCTTA                   GATGACTGGCATCCTTCTGAGAAGGCAATGTATCCTGATTACTTTGCCAAGAGAGAACAGTCGAAG                   AAACTCCGGAGGGAAAGCTGGGAACGAGAGGTTAAGCAGCTGCAGGAGGAAACGCCACCTGGTCGT                   CCTTTAACTGAAGCTTTGCCCCCTGCCCGAAAGGAAGGTGATTTGCCCCCACTGTGGTGGTATATT                   GTGACCAGACCCCCGGAGCGGCCCATG TAG   AAAGAGAGAGACCTCATCTTTCATGCTTGCAAGTGA                       AATATGTTACAGAACATGCACTTGCCCTAATAAAAAATCAGTGAAATGGTCAAAAAAAAAAAAAAA                       AA                                           ORF Start: ATG at 85       ORF Stop: TAG at 622           SEQ ID NO:10   179 aa   MW at 21830.7 kD                     NOV2c,   MAFLASGPYLTHQQKVLRLYKRALRHLESWCVQRDKYRYFACLMRARFEEHKWEKDMAKATQLLKE       CG112559-01       Protein Sequence   AEEEFWYRQHPQPYIFPDSPGGTSYERYDCYKVPEWCLDDWHPSEKAMYPDYFAKREQWKKLRRES                   WEREVKQLQEETPPCGPLTEALPPARKEGDLPPLWWYIVTRPRERPM                  
 
     [0364] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 2B.  
               TABLE 2B                          Comparison of NOV2a against NOV2b and NOV2c.                                     NOV2a   Identities/               Residues/   Similarities           Protein   Match   for the           Sequence   Residues   Matched Region                       NOV2b   1 . . . 50   50/50 (100%)               1 . . . 50   50/50 (100%)           NOV2c    1 . . . 179   179/179 (100%)                 1 . . . 179   179/179 (100%)                       
 
     [0365] Further analysis of the NOV2a protein yielded the following properties shown in Table 2C.  
               TABLE 2C                       Protein Sequence Properties NOV2a                                        SignalP   No Known Signal Sequence Predicted       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 0; pos. chg 0; neg. chg 0           H-region: length 14; peak value 7.59           PSG score: 3.19           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −6.98           possible cleavage site: between 13 and 14           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 11.62 (at 1)           ALOM score: 11.62 (number of TMSs: 0)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 6           Charge difference: 5.0 C(6.0)-N(1.0)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt;Caution: Inconsistent mtop result with signal peptide           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   3   Hyd Moment (75):   0.61           Hyd Moment (95):   0.61   G content:   1           D/E content:   1   S/T content:   2                         Score: −3.54           Gavel: prediction of cleavage sites for mitochondrial preseq           R-2 motif at 35 LRH|LE           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 17.3%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: nuclear           Reliability: 55.5           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           43.5%: mitochondrial           43.5%: nuclear            8.7%: cytoplasmic            4.3%: peroxisomal           &gt;&gt; prediction for CG112559-03 is mit (k = 23)                  
 
     [0366] A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2D.  
               TABLE 2D                          Geneseq Results for NOV2a                                         NOV2a   Identities/                   Residues/   Similarities       Geneseq   Protein/Organism/Length   Match   for the   Expect       Identifier   [Patent #, Date]   Residues   Matched Region   Value               ABP41219   Human ovarian antigen HVCAH21,   1 . . . 179   179/179 (100%)   e−110           SEQ ID NO: 2351 -  Homo sapiens ,   27 . . . 205    179/179 (100%)           205 aa. [WO200200677-A1,           03 JAN. 2002]       AAY32426   Ubiquinone oxidoreductase subunit   1 . . . 179   179/179 (100%)   e−110           CI-B22 homologue CBNAFA09 -   1 . . . 179   179/179 (100%)             Homo sapiens , 179 aa.           [WO9962948-A1, 09 DEC. 1999]       AAY66190   Human bladder tumour EST encoded   1 . . . 179   179/179 (100%)   e−110           protein 48 -  Homo sapiens , 206 aa.   28 . . . 206    179/179 (100%)           [DE19818619-A1, 28 OCT. 1999]       AAY76558   Human ovarian tumor EST fragment   10 . . . 179    168/170 (98%)    e−104           encoded protein 54 -  Homo sapiens ,   5 . . . 174   169/170 (98%)            174 aa. [DE19817557-A1,           21 OCT. 1999]       ABG23808   Novel human diagnostic protein   1 . . . 179   165/182 (90%)    5e−97            #23799 -  Homo sapiens , 234 aa.   30 . . . 211    169/182 (92%)            [WO200175067-A2, 11 OCT. 2001]                  
 
     [0367] In a BLAST search of public sequence databases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2E.  
               TABLE 2E                          Public BLASTP Results for NOV2a                                         NOV2a   Identities/           Protein       Residues/   Similarities       Accession       Match   for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value               Q9Y6M9   NADH-ubiquinone oxidoreductase   2 . . . 179    178/178 (100%)   e−109           B22 subunit (EC 1.6.5.3) (EC   1 . . . 178    178/178 (100%)           1.6.99.3) (Complex I-B22) (CI-B22) -             Homo sapiens  (Human), 178 aa.       Q9UQE8   NADH-ubiquinone oxidoreductase   1 . . . 179   178/179 (99%)   e−109           B22 subunit homolog -   1 . . . 179   178/179 (99%)             Homo sapiens             (Human), 179 aa.       S28256   NADH dehydrogenase (ubiquinone)   1 . . . 179   163/179 (91%)   e−101           (EC 1.6.5.3) chain CI-B22 - bovine,   1 . . . 179   173/179 (96%)           179 aa.       Q02369   NADH-ubiquinone oxidoreductase   2 . . . 179   162/178 (91%)   e−101           B22 subunit (EC 1.6.5.3)   1 . . . 178   172/178 (96%)           (EC 1.6.99.3) (Complex I-B22)           (CI-B22) -             Bos taurus  (Bovine), 178 aa.       Q9CQJ8   1190008J14Rik protein (NADH   1 . . . 178   155/178 (87%)   2e−95            dehydrogenase (Ubiquinone)   1 . . . 178   165/178 (92%)           1 beta subcomplex, 9) -             Mus musculus             (Mouse), 179 aa.                  
 
     [0368] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2F.  
               TABLE 2F                       Domain Analysis of NOV2a                                                Pfam   NOV2a   Identities/Similarities   Expect       Domain   Match Region   for the Matched Region   Value                  
 
     Example 3.  
     [0369] 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:11   853 bp                     NOV3a,     GTCGGTAGTAGCG   ATG GCGGGTCTGACTGACTTGCAGCGGCTACAGGCCCGAGTGGAAGAGCTGGA       CG115757-01       DNA Sequence   GCGCTGGGTGTACGGGCCGGGCGGGGCGCGCGGCTCACGCAAGGTGGCTGACGGCCTGGTCAAGGT                   GCAGGTGGCTTTGGGAACATTTCCAGCAAGAGGGAGAGGGTGAAAGATTCTCTACAAAAAGATTGA                   AGATCTGATCAAGTACCTGGATCCTGAGTACATCGACCGCATTGCCATACCTGATGCCTCTAAGCT                   GCATTCATCCTAGCAGAGGAGCAGTTTATCCTTTCCCAGGTTGCACTCCTGGAGCAGAATGAATGC                   TTGGTGCCCATGCTGGACAGTGCTCACATCAAAGCCGTTCCTGAGCATGCTGCCCGGCCTGCAGCG                   TTGGCCCAGATCCACATTCAGCAGCAGCACCAGTGTGTGGAAATCACTGAGGAGTCCAAAGGCTCT                   CTGGAGGAATACAACAAGACTACAATGCTTCTCTCCAAGCAATTCGTGCAGTGGGATGGAGCTACT                   TTGCCAGCTAGAGGCCGCCACGCAAGTGAAGCCAGCAGAGGAG TGA   TAGCTGCTCCCCAATCCCAA                       GTGGGCCTGGGCAGTCAGGCTCCAAAGCCCTATGCCAACCTGCCTTTGTTACAAGGCAGAGGAAGC                       TTTGTATTTATTGGCTTCAAGAACCACCTCTCTGTACTCTGGGCTCTAAAGTTGGAGGTCAGGTTA                       CCTGAGTTTGCAATTTGCAACACCCACCCTCCCCCCAAAACAGTGTTCTTATTTCAGTGACAATAA                       ACCATAGAGATGACTGGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA                                           ORF Start: ATG at 14       ORF Stop: TGA at 572           SEQ ID NO:12   186 aa   MW at 21119.2 kD                     NOV3a,   MAGLTDLQRLQARVEELERNVYGPGGARGSRKVADGLVKVQVALGNISSKRERVKILYKKIEDLIIC       CG115757-01       Protein Sequence   YLDPEYIDRIAIPDASKLQFILAEEQFILSQVALLEQVNALVPMLDSAHIKAVPEHAARLQRLAQI                   HIQQQDQCVEITEESKAILLEEYMKTTMLLSKQFVQWDELLCQLEAATQVKPAEE                                     SEQ ID NO:13   540 bp                     NOV3b,     GTCGGTAGTAGCG   ATG GCGGGTCTGACTGACTTGCAGCCGCTACAGGCCCGAGTGGAAGAGCTGGA       CG115757-02       DNA Sequence   GCGCTGGGTGTACCGGCCGGGCGGGGCGCGCGGCTCACGGAAGGTGGCTGACGGCCTGGTCAAGGT                   GCAGGTGGCTTTGCGGAACATTTCCAGCAAGAGGGAGAGGGTGAAGATTCTCTACAAAAAGATTGA                   AGATCTGATCAAGTACCTGGATCCTGAGTACATCGACCGCATTGCCATACCTGATGCCTCTAAGCT                   GCAATTCATCCTAGCAGCCGTTCCTGAGCATGCTGCCCGCCTGCAGCGCTTGGCCCAGATCCAAAT                   TCAGCAGCAGCACCAGTGTGTGGAAATCACTGAGGAGTCCAAGGCTCTCCTGGAGGAATACAACAA                   GACTACAATGCTTCTCTCCAAGCAATTCGTGCAGTGGGATGAGCTACTTTGCCAGCTAGAGGCCGC                   CACGCAAGTGAAGCCAGCAGAGGAG TGA   TAGCTGCTCCCCATCCCAAAGTGGGCCTGGGCAGTCAG                       GCTCCAGGGCCC                                           ORF Start: ATG at 14       ORF Stop: TGA at 488           SEQ ID NO:14   158 aa   MW at 18000.6 kD                     NOV3b,   MAGLTDLQRLQARVEELERWVYGPGGARGSRKVADGLVKVQVALGNISSKRERVKILYKKIEDLIK       CG115757-02       Protein Sequence   YLDPEYIDRIAIPDASKLQFILAAVPEHAARLQRLAQIHIQQQDQCVEITEESKALLEEYNKTTML                   LSKQFVQWDELLCQLEAATQVKPAEE                  
 
     [0370] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 3B.  
               TABLE 3B                          Comparison of NOV3a against NOV3b.                                 Protein   NOV3a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV3b   1 . . . 186   158/186 (84%)               1 . . . 158   158/186 (84%)                      
 
     [0371] Further analysis of the NOV3a protein yielded the following properties shown in Table 3C.  
               TABLE 3C                       Protein Sequence Properties NOV3a                                        SignalP   No Known Signal Sequence Predicted       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 9; pos. chg 1; neg. chg 1           H-region: length 3; peak value −12.04           PSG score: −16.44           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −5.79           possible cleavage site: between 49 and 50           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 2.44 (at 93)           ALOM score: 2.44 (number of TMSs: 0)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   2   Hyd Moment(75):   1.95           Hyd Moment(95):   4.15   G content:   1           D/E content:   2   S/T content:   1           Score: −6.20                         Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 12.4%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           KKXX-like motif in the C-terminus: KPAE           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern : none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions                                             38   K   0.52                       39   V   0.52           40   Q   0.52           41   V   0.52           42   A   0.52           43   L   0.52           44   G   0.52           45   N   0.52           46   I   0.52           47   S   0.52           48   S   0.52           49   K   0.52           50   R   0.52           51   E   0.52           52   R   0.52           53   V   0.52           54   K   0.52           55   I   0.52           56   L   0.52           57   Y   0.52           58   K   0.52           59   K   0.52           60   I   0.52           61   E   0.52           62   D   0.52           63   L   0.52           64   I   0.52           65   K   0.52                         total: 28 residues           Final Results (k = 9/23):           56.5%: cytoplasmic           26.1%: nuclear            8.7%: mitochondrial            4.3%: vacuolar            4.3%: vesicles of secretory system           &gt;&gt; prediction for CG115757-01 is cyt (k = 23)                  
 
     [0372] A search of the NOV3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3D.  
               TABLE 3D                          Geneseq Results for NOV3a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV3a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value               AAG04042   Human secreted protein, SEQ ID NO:   1 . . . 103   100/103 (97%)    1e−49           8123 -  Homo sapiens , 103 aa.   1 . . . 103   101/103 (97%)            [EP1033401-A2, 06 SEP. 2000]       AAB45191   Human secreted protein sequence   92 . . . 186     95/95 (100%)   2e−47           encoded by gene 21 SEQ ID NO:   1 . . . 95     95/95 (100%)           132 -  Homo sapiens , 95 aa.           [WO200058467-A1, 05 OCT. 2000]       AAB45190   Gene 21 human secreted protein   92 . . . 186     95/95 (100%)   2e−47           homologous amino acid sequence   1 . . . 95     95/95 (100%)           #131 -  Homo sapiens , 95 aa.           [WO200058467-A1, 05 OCT. 2000]       ABB64732     Drosophila melanogaster  polypeptide   7 . . . 186   46/183 (25%)    3e−04           SEQ ID NO 20988 -  Drosophila     4 . . . 183   83/183 (45%)              melanogaster , 192 aa.           [WO200171042-A2, 27 SEP. 2001]       ABB59344     Drosophila melanogaster  polypeptide   7 . . . 175   38/169 (22%)    0.37           SEQ ID NO 4824 -  Drosophila     1007 . . . 1168    76/169 (44%)              melanogaster , 2056 aa.           [WO200171042-A2, 27 SEP. 2001]                  
 
     [0373] In a BLAST search of public sequence databases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3E.  
               TABLE 3E                          Public BLASTP Results for NOV3a                                             Identities/           Protein           Similarities for       Accession       NOV3a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value               O75935   Dynactin subunit -  Homo sapiens     1 . . . 186    186/186 (100%)    e−100           (Human), 186 aa.   1 . . . 186    186/186 (100%)       Q9D039   Dynactin 3 -  Mus musculus     1 . . . 186   176/186 (94%)   4e−94           (Mouse), 186 aa.   1 . . . 186   181/186 (96%)       Q9CR43   Dynactin 3 - Mus musculus   1 . . . 186   175/186 (94%)   2e−93           (Mouse), 186 aa.   1 . . . 186   180/186 (96%)       Q9Z0Y1   Dynactin light chain -  Mus     1 . . . 186   174/186 (93%)   4e−93             musculus  (Mouse), 186 aa.   1 . . . 186   180/186 (96%)       Q9BPU8   Similar to dynactin 3 (p22) -   1 . . . 153   141/154 (91%)   3e−71             Homo sapiens  (Human), 176 aa.   1 . . . 154   147/154 (94%)                  
 
     [0374] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3F.  
               TABLE 3F                       Domain Analysis of NOV3a                                                Pfam   NOV3a   Identities/Similarities   Expect       Domain   Match Region   for the Matched Region   Value                  
 
     Example 4.  
     [0375] 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:15   3570 bp                     NOV4a,     ATCACGCGTATCCAGGCCCAGTCCCGAGGTGTGCTCGCCAGA   ATG GAGTACAAAAAGCTGCTGGAA       CG120781-01       DNA Sequence   CGTAGAGACTCCCTGCTGGTAATCCAGTGGAACATTCGGGCCTTCATGGGGGTCAAGAATTCGCCC                   TGGATGAAGCTCTACTTCAAGATCAAGCCCCTCCTGAAGAGTGCAGAAAGAGAGAAGGAGATGGCC                   TCCATGAAGGAGGAGTTCACACGCCTCAAAGACGCCCTAGAGAAGTCCGAGGCTCCCCGCAACGAA                   TCGGAGGAGAAGATGGTGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAACTGCAGGCGGAA                   CTCGGACAACCTGGCAGATGCTGAGGAGCGCTGTGATCAGCTGATCAAAAACAAGATTCACCTGAG                   CAACAAGGTGAAGGAGATCAACGAGAGGCTGGAGGATGAGGAGGAGATGAATGCTGAGCTCCTGCC                   GCCAAGGTGAAGGAGATGAACGAGAGGCTGGAGGATGAGGAGGAGATGAATGCTGAGCTCACTGCC                   AAGAAGCGCAAGCTGGAAGATGAGTGCTCAGAGCTCAAAACGGACATCGATGATCTGGAGCTGACA                   CTGGCCAAAAGTGGAGAAGGAGAACACGCAACAGAGAACAAGGTGAAAAACCTGACAGAGGAGATG                   GCTGGCTGGAAAGATGAGATCATTGCCAAGCTGACCAAGAGAAGAGCTCTGCAAGAAACCCACCAA                   CAGGGCTCTGGATGACCTTCAGGCCGAGGAGGACAGGTCAACACCCTGACTAAGGCCAAAGTCAAG                   CTGGAGCAGCAGTGGATGATCTGGAAGGATCCCTGGAGCAAGAGAAGAAGGTGCGAATGGAACCTG                   GAGCGAGCGAAGCGGAAGCTGGAGGGCGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAG                   AATGACAAGCAGCAGCTGGAGGAGCGGCTGAAAAAAAAGACTTTGAGCTGAATGCTCTCAACGGCA                   AGGCAGAGGAACTTCGACAAGATCCTGGCCGAGTGGAAGCAGAAGTATGAGGAGTCGCAGTCGGAG                   ATCGAGGAGCTGGAGCAGGAGCTGGAGGCCGAGCGCACCGCCAGGGCTAAGGTGGAGAAGCTGCGC                   TCAGACCTGTCTCGGGAGCTGGAGGAGAAAATGCAGCGAGCGGCTGAAACCGGCAAAACCACGTCC                   GTGCAGATCGAGATGAACAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGAAACCTGGAAAAG                   GCCACCCTGCAGCACGAAGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGTAACCGAG                   CTGGCGAGCAGATCGACAAAGGCCTGCAGCGGGTGAGCAGAAGCTGGAGAAAAGAAGAGCGAGTTC                   AAGCTGGAGCTGGATGACGTCACCTCCAACAAGGAGGGTGGAGCAGATCATCACCCTAACCTAAAC                   AAGATGTGCCGGACCTTGGAAGACCAGATGAATGAGCACCGGAGCAAGGCGGAAAAGACCCAGCGT                   TCTGTCAACGACCTCACCAGCCAGCGGGCCAAGTTCCAAACCGAGAATGGTGAGCTGTCCCGGAAG                   CTGGTGAGGAAGGAGGCACTGATCTCCCAGCTGACCCGAGGCAAGCTCACCTACACCCAGCAGCTG                   GAGGACCTCAACAGGCAGCTGGAGGAGGACGTTAAGGCGAAGAACGCCCTGGCCCACGCACTGCAG                   TCGGCCCCGCATGACTGCGACCTGCTGCGGGAGCAGTACGAGGAGGAGACGGAGGCCAAGGCCGAG                   CTGCAGCGCGTCCTTTCCAGCCGGAAACTCGGAGGTGCCCAGTGGAGGACCAAGTATGAGACAAAC                   GCCTTCAGCGGAACTGAGGAGCTCGAGGAGGCCAAGAAGAAGCTGGCCCAGCGGCTGCAAAAAGCT                   GAGGAGGCCGTGGAGGCTGTTAATGCCAAGTGCTCCTCGCTGGAGAAGACCAAGCACCGGCTACAG                   GATGGAGATCGAGAGACTTGATAATGACGTAGAGCGCTCCATGCTGCTGCTGCAGCCCTAAACAAG                   AGCAGAGGAACTTCAGACAAGATCCTGGCCGACTGGAAGCAGAAGTATGAAAAGTCGCAGTCGGAG                   CTGGAAGTCCTCGGCAGAAGGAGGCTCGCTCCCTCAGCACAGAGCTCTTCAACTAAGAACGCCTAT                   GGAGGAGTCCCTGGAACATCTGGAGACCTTCAAGCGGGAGAACAAAACCTGCAGGAAAAGATCTCC                   GGACTTGACTGAAGCAGTTGGGTTCCAGCGGAAAGACTATCCATGAGCTAAAGAATCCGAAAGCAG                   GTGAGGCCGGAGAAGATGGAGCTGCAGTCAGCCCTGGAGGAGGCCCAAACCTCCCTGGAGCACGAG                   GAGGGGCAAGATCCTCCGGGCCCAGCTGGAGTTCAACCAGATCAGGCAGAGATCGAGCAAAAGCTG                   ACCAGAGAAGGAGGAGAGGAGATGACAGGCCAAGCGcACCACCTGCGAATGGTAAACTCGCTGCAG                   GAGTTGCGTGCCGTGGTGGAGCAGACAGAGCGGTCCCGGAACCTGGCGGACGAGGAGCTGATTGAG                   GACCTCAATGAGATGGAGATCCAGCTCAGCCACGCCAACCGCATAACCGCCGAGGCCCACAAGCAA                   GTCAAGAGCCTCCAGAGCTTGTTGAAGGACACCCAGATTCAGCTGGACGATGCAGTCCGTGCCAAC                   GAGGACCTGAAGGAGAACATCGCCATCGTGGAGCGGCGCAACAACCTGCTCCAGGCTGAGCTGGAC                   GAGTTGCGTCCCGTGGTGGAGCAGACAGAGCGGTCCCGGAAGCTGGCAAACGAGCAGCTGATTGAG                   ACTAGTGAGCGGGTGCAGCTGCTGCATTCCCAGAACACCAGCCTCATCAACCAGAAGAAGAAGATG                   GATGCTGACCTGTCCCACCTCCAGACTGAAGTGGAGGACGCAGTGCAGGAGTCCAGGAATGCTGAG                   GAGAAGGCCAGAAGGCCAATCACGGATGCCGCCATGATGGCAGAGGAGCTGAAGAAGGAGCAAAAC                   ACCAGCGCCCACCTGGAGCGCATGAGGAAAAGAACATGGAACAGACCATTAAACCTGCAGCACCAA                   CTGGACGAAGCCGAGCAGATCGCCCTCAAGGGCGGCAAGAAGCAGCTGCAGAAGCTGGAAGCGCGG                   GTGCGGAGCTGGGAGAATGAGCTGGAGGCCGAGCAGAAGCGCAACGCAGAGTCAATGAAGAACATG                   AGGAAGAGCGAGCGGCGCATCAAGGAGCTCACCTACCAGACGGAGCAAAACAGGAAAAACCTGCTG                   CGGCTGCAGGACCTGGTAGACAAGCTGCAGCTAAAGGTCAAGGCCTACAAGCGCCAGGCCGAGGAG                   GCGGAGGAGCAAGCCAACACCAACCTGTCCAAGTTCCGCAAGGTGCAGCACGACCTGGATGAGGCA                   GAGGAGCGGGCGGACATCGCCGAGTCCCAGGTCAACAACCTGCGGGCCAAGAGCCGTGACATTGGC                   ACGAAGGGCTTGAATGAGGAG TAG   CTTTGCCACATCTTGATCTGCTCAGCCCTGGAAATGCCAGCA                       AAGCCCCAATGCTGGAGCCTGTGTACAGCTCCTTGGGAGGAAGCAGAATAAGCAATTTTCCTTGA                       AGCCGA                                           ORF Start: ATG at 43       ORF Stop: TAG at 3454           SEQ ID NO:16   1137 aa   MW at 132393.8 kD                      NOV4a,   MEYKKLLERRDSLLVTQWNIRAFMGVKNWPWMKLYFKIKPLLKSAEREKEMASMKEEFTRLKEALE       CG120781-01       Protein Sequence   KSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLADAEERCDQLIKNKIQLEAKVKEMAAERLEDEE                   EMANAELTAKKRKLEDECSELKRDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEK                   KALQEAHQQALDDLQAEEDKVNTLTKAKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLT                   QESIMDLENDKQQLEERLKKKDFELNALNARIEDEQALGSQLQKKLKELQARIEELEEELEAERTA                   RAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRK                   KHADSVAELGEQIDAALQRVKQKLEKEKSEFKLELDDVTSNMEQIKAKANLEKMCRTLEDQMNEHR                   SKAEETQRSVNDLTSQRAKLQTENGELSRQLDEKEALISQLTRGKLTYTQQLEDLKRQLEEEVKAK                   NALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEELEEAKKK                   LAQRLQEAEEAVEAVNAKCSSLEKTKHRLQNEIELMVDVERSIAAAAALDKKQRNFDKILAAEWKG                   KYEESQSELESSQKEARSLSTELFKLAAAYEESLEHLETFKENAALQEEISDRLTEQAASSGKTIH                   ELEKVRKQLEAEKMELQSALEEAEASLEHEEGKILRAQLEFNQIKAEERKLAEKDEEEMEQAKRNH                   LRVVDSLQTSLDAETRSRNEALRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQ                   LDDAVRANDDLKENIAIVERRNNLLQAELEELRAVVEQTERSRKLADEELIETSERVQLLHSQNTS                   LINOKKKMDADLSQLQTEVEEAVQECRNAEEKAKKAITDAAMMAEELKKEQDTSAIHERNKKNMEQ                   TIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELEAAELEAEQKRNESVKGMRKSERRIKELTYQT                   EEDRKNLLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAESQVNKL                   RARSRDIGTKGLNEE                                     SEQ ID NO:17   4775 bp                     NOV4b,     TGTCTTTCCCTGCTGCTCTCAGGTCCCCTGCAGGCCTTGGCCCCTTTCCTCATCTGTAGACACACT         CG120781-03       DNA Sequence     TGAGTAGCCCAGGCACAGCC   ATG GGAGATTCGGAGATGGCAGTCTTTGGGGCTGCCGCCCCCTACC                   TGCGCAGTCAACAGAAGGAGCGGCTAGAAGCGCAGACCACGCCTTTTGACCTCAAGAACGATGTCT                   TCGTGCCTGATGACAAACAGGAGTTTGTCAAGGCCAAGATCGTGTCTCGAGAGGGTGGCAAAGTCA                   CTGCCGAGACTGAGTATGGCAAGACAGTGACCGTGAAGGAGGACCAGGTGATGCAGCAGAACCCAC                   CCAAGTTCGACAAAATCGAGGACATGGCCATGCTGACCTTCCTGCATGAGCCCGCGGTGCTCTACA                   ACCTCAAGGATCGCTACGGCTCCTCGATGATCTACACCTACTCGCGCCTCTTCTGTGTCACCGTCA                   ACCCTTACAAGTGGCTGCCGGTGTACACTCCTGAGGTGGTGGCTCCCTACCGGGGCAAGAAGAGGA                   GCGAGGCCCCGCCCCACATCTTCTCCATCTCCGACAACGCCTATCAGTACATGCTGACAGACAGAG                   AAAACCAGTCCATCCTGATCACCGGAGAATCCGGAGCAGGGAAGACAGTCAACACCAAGAGGGTCA                   TCCAGTACTTTGCTGTTATTGCAGCCATTGGGGACCGCAGCAAGAAGGACCAGAGCCCGGGCAAGG                   GCACCCTGGAGGACCAGATCATCCAGGCCAACCCTGCTCTGGAGGCCTTTGGCAATGCCAAGACCG                   TCCGGAACGACAACTCCTCCCGCTTCGGGAAATTCATTCGAATTCATTTTGGGGCAACAGGAAAGT                   TGGCATCTGCAGACATAGAGACCTATCTTCTGGAAAAATCCAGAGTTATTTTCCAGCTGAAAGCAG                   AGAGAGATTATCACATTTTCTACCAAATCCTGTCTAACAAAAAGCCTGAGCTGCTGGACATGCTGC                   TGATCACCAACAACCCCTACGATTATGCATTCATCTCCCAAGGAGAGACCACCGTGGCCTCCATTG                   ATGACGCTGAGGAGCTCATGGCCACTGATAACGCTTTTGATGTGCTGGGCTTCACTTCAGAGGAGA                   AAAACTCCATGTATAAGCTGACAGGCGCCATCATGCACTTTGGAAACATGAAGTTCAAGCTGAAGC                   AGCGGGAGGAGCAGGCGGAGCCAGACGGCACTGAAGAGGCTGACAAGTCTGCCTACCTCATGGGGC                   TGAACTCAGCCGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAAGTGGGCAATGAGTACGTCA                   CCAAGGGGCAGAATGTCCAGCAGGTGATATATGCCACTGGGGCACTCGCCAAGGCAGTGTATGAGA                   GGATGTTCAACTGGATGGTGACGCGCATCAATGCCACCCTGGAGACCAAGCAGCCACGCCAGTACT                   TCATAGGAGTCCTGGACATCGCTGGCTTCGAGATCTTCCATTTCAACAGCTTTCAGCAGCTCTGCA                   TCAACTTCACCAACGAGAAGCTGCAGCAGTTCTTCAACCACCACATGTTTGTGCTCGAGCAGGAGG                   AGTACAAGAAGGAGGGCATCGAGTGGACATTCATTGACTTTGGCATGGACCTGCAGGCCTGCATTG                   ACCTCATCGAGAAGCCCATGGGCATCATGTCCATCCTGGAAGAGGAGTGCATGTTCCCCAAGGCCA                   CCGACATGACCTTCAAGGCCAAGCTGTTTGACAACCACCTGGCCAAATCCGCCAACTTCCAGAAGC                   CACGAAATATCAAGGGGAAGCCTGAAGCCCACTTCTCCCTGATCCACTATGCCGGCATCGTGGACT                   ACAACATCATTGGCTGGCTGCAGAAGAACAAGGATCCTCTCAATGAGACTGTCGTGGGCTTGTATC                   AGAAGTCTTCCCTCAAGTTGCTCAGCACCCTGTTTGCCAACTATGCTGGGGCTGATGCGCCTATTG                   AGAACGCCAAAGGCAAGGCCAAGAAAGGCTCGTCCTTTCAGACTGTGTCAGCTCTGCACAGGGAAA                   ATCTGAACAAGCTGATGACCAACTTGCGCTCCACCCATCCCCACTTTGTACGTTGTATCATCCCTA                   ATGAGACAAAGTCTCCAGGCGTGATGGACAACCCCCTGGTCATGCACCAGCTGCGCTGCAATGGTG                   TGCTGGAGGGCATCCGCATCTGCAGGAAAGGCTTCCCCAACCGCATCCTCTACGGGGACTTCCGGC                   AGAGGTATCGCATCCTCAACCCAGCGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGG                   CAGAGAAGCTGCTCAGCTCCCTGGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAGGTGT                   TCTTCAAGGCCGGGCTGCTGGGGCTGCTGGAGGAAATGAGGGACGAGAGGCTGAGCCGCATCATCA                   CGCGTATCCAGGCCCAGTCCCGAGGTGTGCTCGCCAGAATGGAGTACAAAAAGCTGCTGGAACGTA                   GAGACTCCCTGCTGGTAATCCAGTGGAACATTCGGGCCTTCATGGGGGTCAAGAATTGGCCCTGGA                   TGAAGCTCTACTTCAAGATCAAGCCGCTGCTGAAGAGTGCAGAAAGAGAGAAGGAGATGGCCTCCA                   TGAAGGAGGAGTTCACACGCCTCAAAGACGCCCTAGAGAAGTCCGAGGCTCGCCGCAAGGAGCTGG                   CAGGAGAAGATGGTGTCCCTGCTGCAGGAGAGAATGACCTGCACCTCCAAGTGCAGGCGGAACAAG                   ACAACCTGGCAGATGCTGAGGAGCGCTGTGATCAGCTGATCAAAACAAGATTCAGCTGGAGAACTA                   AGGTGAAGGAGATGAACGAGAGGCTGGAGGATGAGGAGGAGATGAATGCTGAGCTCACTGCCAAGA                   AGCGCAAGTTGGAAGATGAGTGCTCAGAGCTCAAAAGGGACATCGATGATCTCGAGCTGACACTGG                   CCAAAGTGGAGAAGGAGAAACACGCAACAGAGAACAAGGTGAAAAACCTGACAGAGGAGATGGCTG                   GGCTGGATGAGATCATTGCCAAGCTGACCAAGGAGAAGAAAGCTCTGCAAGAGGCCCACCAACAGG                   CTCTGGATGACCTTCAGGCCGAGGAGGACAAGGTCAACACCCTGACTAAGGCCAAAGTCAAGCTCG                   ACCAGCAAGTGGATGATCTGGAAGGATCCCTGGAGCAAGAGAAGAAGGTGCGCATGCACCTCGAGC                   CAGCGAAGCGGAAGCTGGAGGGCGACCTGAAGCTGACCCAGGAGAGCATCATCGACCTGGAGAATG                   ACAAGCAGCAGCTCGATGAGCGGCTGAAAAAAAAAGACTTTGAGCTGAATGCTCTCAACGCAAGGA                   TTGAGGATGAACAGGCCCTCGGCAGCCAGCTGCAGAAGAAGCTCAAGGAGCTTCAGGCACGCATCG                   CAGGAGCTGGAGGAGGAGCTGACGCCGAGAAGATGGAGCTGCAGTCAGCCCTGGAGGAGGCCGAGG                   CCTCCCTGGAGCACGAGGAGGGCAAGATCCTCCGGGCCCAGCTGGAGTTCAACCAGATCAAGGCAG                   AGATCGAGCGGAAGCTGGCAGAGAAGGACGAGGAGATGGAACAGGCCAAGCGCAACCACCTGCGGG                   TGGTGGACTCGCTGCAGACCTCCCTGGACGCAGAGACACGCAGCCGCAACGAGCCCCTGAGGGTGA                   AGAAGAAGATGGAAGGAGACCTCAATGAGATGGAGATCCAGCTCAGCCACGCCAACCCCATGGCCG                   CCGAGGCCCAGAAGCAAGTCAAGAGCCTCCAGAGCTTGTTGAAGGACACCCAGATTCAGCTGGACG                   ATGCAGTCCGTGCCAACGACGACCTGAAGGAGAACATCGCCATCGTGGAGCGGCGCAACAACCTGC                   TGCAGGCTGAGCTGGAGGAGTTGCGTGCCGTGGTGGAGCAGACAGAGCGGTCCCGGAAGCTGGCGG                   AGCAGGAGCTGATTGAGACTAGTGAGCGGGTGCAGCTGCTGCATTCCCAGAACACCACCCTCATCA                   ACCAGAAGAAGAAGATGGATGCTGACCTGTCCCAGCTCCACACTGAAGTGGAGGAGGCAGTGCAGG                   AGTGCAGGAATGCTGAGGAGAAGGCCAAGAACGCCATCACGGATGCCGCCATGATGGCAGAGGAGC                   TGAAGAAGGAGCAGGACACCAGCGCCCACCTGGAGCGCATGAAGAACAACATGCAACAGACCATTA                   CAGGACCTGCAGCACCGGCTGACGAAGCCGAGCAGATCGCCCTCAAGGGCGGCAAGAAGCAGCTGC                   AGAAGCTCGAAGCGCGGGTGCGGGAGCTGGAGAATGAGCTGGAGGCCCAGCAGAAGCGCAACGCAG                   AGTCGGTGAAGGGCATGAGGAAGAGCGAGCGGCGCATCAACGAGCTCACCTACCAGACGGAGGAGG                   ACAGGAAAAACCTGCTGCGGCTGCAGGACCTCGTAGACAAGCTGCAGCTAAAGGTCAAGGCCTACA                   AGCGCCAGGCCGAGGAGGCGGAGGAGCAAGCCAACACCAACCTGTCCAAGTTCCGCAACGTCCAGC                   ACGAGCTGCATGAGGCAGAGGAGCGGGCGGACATCGCCGAGTCCCACGTCAACAAGCTGCGGGCCA                   AGAGCCGTGACATTGGCACGAACGGCTTGAATGAGGAG TAG   CTTTGCCACATCTTGATCTGCTCAG                       CCCTGGAGGTGCCAGCAAAGCCCCATGCTGGAGCCTGTGTAACAGCTCCTTGGGAGGAAGCAGAAT                       AAAGCAATTTTCCTTGAAGCCGA                                           ORF: Start: ATG at 87       ORF Stop: TAG at 4659           SEQ ID NO:18   11524 aa   MW at 175519.4 kD                     NOV4b,   MGDSEMAVFGAAAPYLRKSEKERLEAQTRPFDLKKDVFVPDDKOEFVKAKIVSREGGKVTAETEYG       CG120781-03       Protein Sequence   KTVTVKEDQVMQQNPPKFDKTEDMAMLTFLHEPAVLYNLKDRYGSWMIYTYSGLFCVTVNPYKWLP                   VYTPEVVAAYRGKKRSEAPPMIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFAVT                   AAIGDRSKKDQSPGKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIRIHFGATGKLASADIE                   TYLLEKSRVIFQLKAERDYHIFYQILSNKKPELLDMLLITNNPYDYAFISQGETTVASIDDAEELM                   ATDNAFDVLGFTSEEKNSMYKLTGAIMHFGNMKFKLKQREEQAEPDGTEEADKSAYLMGLNSADLL                   KGLCHPRVKVGNEYVTKGQNVQQVIYATGAIAKAVYERNFNWMVTRINATLETKQPRQYFIGVLDI                   AGFEIFDFNSFEQLCINFTNEKLQQFFNIIMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKPM                   GINSILEEECMFPKATDMTFKAKLFDNHLGKSANFQKPRPIKGKPEAHFSLIHYAGIVDYNIIGWL                   QKNKOPLNETVVGLYQKSSLKLLSTLFANYAGADAPIEKGKGKAKKGSSFQTVSALHRENLNKLMT                   NLRSTHPHPVRCIPNETKSPGVMDNPLVMIIQLRCNGVLEGIRICRKGEPNRILYGDFRQRYRILN                   PAAIPEGOFIDSRKGAEKLLSSLDIDHNQYKFGHTFVFFKAGLLGLLEEMRDERLSRIITRIQAQS                   RGVLARNEYKKLLERRDSLLVIONNIRAFMGVKNWPWMKLYFKIKPLLKSAEREKEMASMKEEPTR                   LKEILEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLADAEERCDQLTKNKIQLEAKVKEMNE                   RGVEDEEEMNAELTAKKRKLEDECSELKRDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIA                   KLTKEKKALQEAHQQALDDLQAEEDKVNTLTKAKVKLEQQVDDLEGSLEQECKVRMDLERAKRKLE                   GDLKLTQESIMDLENDKQQLDERLKKKDFELNALNARIEDEQALGSQLQKKLKELQARIEELEEEL                   EAEKMELQSALEEAEASLEHEEGKILRAQLEFNQIKAEIRKTIAEKDEEMEQAKRNMLRVVDSLQT                   SLDAETRSRNEALRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRAND                   DLKENIAIVERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMD                   ADLSQLQTEVEEAVQECRNAEEKAKKAITDANMAEELKKEQDTSAIILERNKKNMEQTIKDLQHRL                   DEAEQIALKGGKKQLQKLEARVRELENELEAEQKRNAESVKGMRKSERRIKELTYQTEEDRKNLLR                   LQDLVDKOLKVKAYKJQAEEAEEQATNTNLSKFRKVQHELDEASERADIAESQVNKLRAKSRDIGT                   KGLNEE                                     SEQ ID NO:19   5780 bp                     NOV4c,     TGTCTTTCCCTGCTGCTCTCAGGTCCCCTGCAGGCCTTGGCCCCTTTCCTCATCTGTAGACACACT         CG120781-04       DNA Sequence     TGAGTAGCCCAGGCACAGCC   ATG GGAGATTCGGAGATGGCAGTCTTTGGGGCTGCCGCCCCCTACC                   TGCGCAAGTCAGAGAAGGAGCGGCTAGAAGCGCAGACCAGGCCTTTTGACCTCAAGAAGGATGTCT                   TCGTGCCTGATGACAAACAGGAGTTTGTCAAGGCCAAGATCGTGTCTCGAGAGGGTGGCAAAGTCA                   CTGCCGAGACTGAGTATGGCAAGACAGTGACCGTGAAGGAGGACCAGGTGATGCAGCAGAACCCAC                   CCAAGTTCGACAAAATCGAGGAGATGGCCATGCTGACCTTCCTGCATGAGCCCGCGGTGCTCTACA                   ACCTCAAGGATCGCTACGGCTCCTGGATGATCThCACCTACTCGGGCCTCTTCTGTGTCACCGTCA                   ACCCTTACAAGTGGGTGCCGGTGTACACTCCTGAGGTGGTGGCTGCCTACCGGGGCAAGAAGAGGA                   CCGAGGCCCCGCCCCACATCTTCTCCATCTCCGACAACGCCTATCAGTACATGCTGACAGACAGAG                   AAAACCAGTCCATCCTGATCACCGGAGAATCCGGAGCAGGGAAGACAGTCAACACCAAGAGGGTCA                   TCCAGTACTTTGCTGTTATTGCAGCCATTGGGGACCGCAGCAAGAACGACCAGAGCCCGGGCAAGG                   GCACCCTGGAGGACCAGATCATCCAGGCCAACCCTGCTCTGGAGGCCTTTGGCAATGCCAAGACCG                   TCCCGAACGACAACTCCTCCCGCTTCGGGAAATTCATTCGAATTCATTTTGGGGCAACAGGAAAGT                   TGGCATCTGCAGACATAGAGACCTATCTTCTGGAAAAATCCAGAGTTATTTTCCAGCTGAAAGCAG                   AGAGAGATTATCACATTTTCTACCAAATCCTGTCTAACAAAAAGCCTGAGCTGCTGGACATGCTGC                   TGATCACCAACAACCCCTACGATTATGCATTCATCTCCCAAGGAGAGACCACCGTGGCCTCCATTG                   ATGACGCTGAGGAGCTCATGGCCACTGATAACGCTTTTGATGTGCTGGGCTTCACTTCAGAGGAGA                   AAAACTCCATGTATAAGCTGACAGGCGCCATCATGCACTTTGGAAACATGAAGTTCAAGCTGAAGC                   AGCGGGAGGAGCAGGCGGAGCCAGACGGCACTGAAGAGGCTGACAAGTCTGCCTACCTCATGGGGC                   TGAACTCAGCCGACCTGCTCAAGGGGCTGTGCCACCCTCCGGTGAAAGTGGGCAATGAGTACGTCA                   CCAAGGGGCAGAATGTCCAGCACGTGATATATGCCACTGGGGCACTGGCCAAGGCAGTGTATGACA                   GGATGTTCAACTGGATCGTGACGCCCATCAATGCCACCCTGGAGACCAAGCAGCCACGCCAGTACT                   TCATAGGAGTCCTGGACATCGCTGGCTTCGAGATCTTCGATTTCAACAGCTTTGAGCAGCTCTGCA                   TCAACTTCACCAACGAGAAGCTGCAGCAGTTCTTCAACCACCACATGTTTGTGCTGGAGCAGGAGG                   AGTACAAGAAGGAGGGCATCGAGTGGACATTCATTGACTTTCGCATGGACCTGCAGGCCTGCATTG                   ACCTCATCGAGAAGCCCATGGGCATCATGTCCATCCTGGAAGAGGAGTGCATGTTCCCCAAGGCCA                   CCGACATGACCTTCAACGCCAAGCTGTTTGACAACCACCTGGGCAAATCCGCCAACTTCCAGAAGC                   CACGAAATATCAAGGGGAAGCCTGAAGCCCACTTCTCCCTGATCCACTATGCCGGCATCGTGGACT                   ACAACATCATTGGCTGGCTGCAGAAGAACAAGGATCCTCTCAATGAGACTGTCGTGGGCTTGTATC                   AGAAGTCTTCCCTCAAGTTGCTCAGCACCCTGTTTGCCAACTATGCTGGGGCTGATGCGCCTATTG                   AGAAGGGCAAAGGCAACGCCAAGAAAGGCTCGTCCTTTCAGACTGTGTCAGCTCTGCACAGGGAAA                   ATCTGAACAAGCTGATGACCAACTTGCGCTCCACCCATCCCCACTTTGTACGTTGTATCATCCCTA                   ATGAGACAAAGTCTCCAGGCGTGATGGACAACCCCCTGGTCATGCACCAGCTGCGCTGCAATGGTG                   TGCTGGAGCCCATCCGCATCTGCAGGAAAGGCTTCCCCAACCGCATCCTCTACGCGGACTTCCCGC                   AGAGGTATCCCATCCTGAACCCAGCGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGG                   CACAGAAGCTGCTCAGCTCCCTGGACATTGATCACAACCAGTACAAGTTTGGCCACACCAAGGTGT                   TCTTCAACGCCGGGCTGCTCGCGCTGCTGCACGAAATGAGGGACCAGAGGCTGAGCCGCATCATCA                   CGCGTATCCACCCCCAGTCCCGAGGTGTGCTCGCCAGAATGGAGTACAAAAAGCTCCTGGAACGTA                   GAGACTCCCTGCTGGTAATCCAGTGGAACATTCGGGCCTTCATCGGGGTCAAGAATTGGCCCTGGA                   TGAAGCTCTACTTCAAGATCAAGCCGCTGCTGAAGAGTGCAGAAAGAGAGAAGGAGATGGCCTCCA                   TGAAGGAGGAGTTCACACCCCTCAAAGAGGCGCTACACAAGTCCCAGGCTCGCCCCAACGACCTGG                   AGGAGAAGATGTGGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAAGTGCAGGCGGAACAAG                   ACAACCTGGCAGATGCTGAGGAGCGCTGTGATCAGCTGATCAAAAACAAGATTCAGCTGGAGGCTA                   AGGTGAAGGAGATGAACGAGAGGCTGGAGGATGAGGAGGAGATGAATGCTGAGCTCACTGCCAAGA                   AGCGCAAGTTGGAAGATGAGTGCTCAGAGCTCAAAAGGGACATCGATGATCTGGAGCTGACACTGG                   CCAAAGTCGAGAAGGAGAAACACGCAACAGAGAACAAGGTCAAAAACCTGACAGAGGAGATGGCTG                   GGCTGGATGAGATCATTGCCAAGCTGACCAAGGAGAAGAAAGCTCTGCAAGAGGCCCACCAACAGG                   CTCTGGATGACCTTCAGGCCGAGGAGGACAAGGTCAACACCCTGACTAAGGCCAAAGTCAAGCTGG                   AGCAGCAAGTGGATGATCTGGAAGGATCCCTGGAGCAAGAGAAGAAGGTGCGCATGGACCTGGAGC                   GAGCGAAGCGGAAGCTGGAGGGCGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAGAATG                   ACAAGCAGCAGCTGGATGAGCGGCTGAAAAAAAAAGACTTTGAGCTGAATGCTCTCAACGCAAGGA                   TTGAGGATGAACAGGCCCTCGGCAGCCAGCTGCAGAAGAAGCTCAAGGAGCTTCAGGCACGCATCG                   AGGAGCTCGAGGAGGAGCTGGAGTCCGAGCGCACCGCCAGGGCTAAGGTGGAGAAGCTGCGCTCAG                   ACCTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTGGAAGAGGCCGGCGGGGCCACGTCCGTGC                   AGATCGAGATGAACAAGAAGCGCGACGCCGAGTTCCAGAAGATGCGGCGGGACCTGGAGGAGGCCA                   CGCTGCAGCACGAGGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTGG                   GCGAGCAGATCGACAACCTGCAGCGGGTGAAGCAGAAGCTGGAGAAGGAGAAGAGCGAGTTCAAGC                   TGGAGCTGGATGACGTCACCTCCAACATGGAGCAGATCATCAAGGCCAAGGCTAACCTGGAGAAGA                   TGTGCCGGACCTTGGAAGACCAGATGAATGAGCACCGGAGCAAGGCGGAGGAGACCCAGCGTTCTG                   TCAACGACCTCACCAGCCAGCGGGCCAAGTTGCAAACCGAGAATGGTGAGCTGTCCCGGCAGCTGG                   ATGAGAAGGAGGCACTGATCTCCCAGCTGACCCGAGGCAAGCTCACCTACACCCAGCAGCTGGAGG                   ACCTCAAGAGGCAGCTGGAGGAGGAGGTTAAGGCGAAGAACGCCCTGGCCCACGCACTGCAGTCGG                   CCCGGCATGACTGCGACCTGCTGCGGGAGCAGTACGAGGAGGAGACGGAGGCCAAGGCCGAGCTGC                   AGCGCGTCCTTTCCAAGGCCAACTCCGAGGTGGCCCAGTGGAGGACCAAGTATGAGACGGACGCCA                   TTCAGCGGACTGAGGAGCTCGAGGAGGCCAAGAAGAAGCTGGCCCAGCGGCTGCAGGAAGCTGAGG                   AGGCCGTGGAGGCTGTTAATGCCAAGTGCTCCTCGCTGGAGAAGACCAAGCACCGGCTACAGAATG                   AGATCGAGGACTTGATCGTGGACGTAGAGCGCTCCAATGCTGCTGCTGCAGCCCTGGACAAGAAGC                   AGAGGAACTTCGACAAGATCCTGGCCGAGTGGAAGCAGAAGTATGAGGAGTCGCAGTCGGAGCTGG                   AGTCCTCGCAGAAGGAGGCTCGCTCCCTCAGCACAGAGCTCTTCAAACTCAAGAACGCCTATGAGG                   AGTCCCTGGAACATCTGGAGACCTTCAAGCGGGAGAACAAAAACCTGCAGGAGGAGATCTCCGACT                   TGACTGAGCAGTTGGGTTCCAGCGGAAAGACTATCCATGAGCTGGAGAAGGTCCGAAAGCAGCTGG                   AGGCCGAGAAGATGGAGCTGCAGTCAGCCCTGGAGGAGGCCGAGGCCTCCCTGGAGCACGAGGAGG                   GCAAGATCCTCCGGGCCCAGCTGGAGTTCAACCAGATCAAGGCAGAGATCGAGCGGAAGCTGGCAG                   AGAAGGACGAGGAGATGGAACAGGCCAAGCGCAACCACCTGCGGGTGGTGGACTCGCTGCAGACCT                   CCCTGGACGCAGAGACACGCAGCCGCAACGAGGCCCTGAGGGTGAAGAAGAAGCAGACAGAGCGGT                   CCCGGAAGCTGGCGGAGCAGGAGCTGATTGAGACTAGTGAGCGGGTGCAGCTGCTGCATTCCCAGA                   ACACCAGCCTCATCAACCAGAAGAAGAAGATGGATGCTGACCTGTCCCAGCTCCAGACTGAAGTGG                   AGGAGGCAGTGCAGGAGTGCAGGAATGCTGAGGAGAAGGCCAAGAAGGCCATCACGGATGCCGCCA                   TGATGGCAGAGGAGCTGAAGAAGGAGCAGGACACCAGCGCCCACCTGGAGCGCATGAAGAAGAACA                   TGGAACAGACCATTAACGACCTGCAGCACCGGCTGGACGAAGCCGAGCAGATCGCCCTCAAGGGCG                   GCAAGAAGCAGCTGCAGAAGCTGGAAGCGCGGGTGCGGGAGCTGGAGAATGAGCTGGAGGCCGAGC                   AGAAGCGCAACGCAGAGTCGGTGAAGGGCATGAGGAAGAGCGAGCGGCGCATCAAGGAGCTCACCT                   ACCAGACGGAGGAGGACAGGAAAAACCTGCTCCGGCTGCAGGACCTGGTAGACAAGCTGCAGCTAA                   AGGTCAAGGCCTACAAGCGCCAGGCCGAGGAGGCGGAGGAGCAAGCCAACACCAACCTGTCCAAGT                   TCCGCAAGGTGCAGCACGAGCTGGATGAGGCAGAGGAGCGGGCGGACATCGCCGAGTCCCAGGTCA                   ACAAGCTGCGGGCCAAGAGCCGTGACATTGGCACGAAGGGCTTGAATGAGGAG TAG   CTTTGCCACA                       TCTTGATCTGCTCAGCCCTGGAGGTGCCAGCAAAGCCCCATGCTGGAGCCTGTGTAACAGCTCCTT                       GGGAGGAAGCAGAATAAAGCAATTTTCCTTGAAGCCGA                                           ORF Start ATG at 87       ORF Stop: TAG at 5664           SEQ ID NO:20   1859 aa   MW at 214471.3 kD                     NOV4c,   MGDSEMAVFGAAAPYLRKSEKERLEAQTRPFDLKKDVFVPDDKQEFVKAKIVSREGGKVTAETEYG       CG120781-04       Protein Sequence   KTVTVKEDQVMQQNPPKFDKIEDMAMLTFLHEPAVLYNLKDRYGSWMIYTYSGLFCVTVNPYKWLP                   VYTPEVVAAYRGKKRSEAPPHIFSISDNAYQYMLTDRENQSILITGESGAGKTVNTKRVIQYFAVI                   AAIGDRSKKDQSFGKGTLEDQIIQANPALEAFGNAKTVRNDNSSRFGKFIRIHFGATGKLASADTE                   TYLLEKSRVIFQLKAERDYHIFYQILSNKKPELLDMLLITNNPYDYAFISQGETTVASIDDAEELM                   ATDNAFDVLGFTSEEKISMYKLTCAIMMFGNMKFKLKQREEQAEPDGTEEADKSAYLMGLNSADLL                   KGLCHPRVKVGNEYVTKGQNVQQVIYATGALAKAVYERMFNWNVTRINATLETKQPRQYFIGVLDI                   AGFEIFDFNSFEQLCINFTINIEKLQQFNHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLTEKPM                   GTMSILEEECMFPKATDMTFKAKLFDNHLCKSANFQKPRNIKGKPEAHFSLIHYAGIVDYNIIGWL                   QKNKDPLNETVVGLYQKSSLKLLSTLFANYAGADAPIEKGKGKAKKOSSFQTVSALHREITNKLMT                   NLRSTHPHFVRCTIPNETKSPGVMDNPLVMHQLRCNQVLEGTRICRKGFPNRILYGDFRQRYRTLN                   PAAIPEGQFTDSRKGAEKLLSSIDIDHNQYKFGHTKVFFKAGLLGLLEEMRDERLSRIITRIQAQS                   RGVLARMEYKKLLERRDSLLVIQWNIRAFMGVKNWPWNKLYFKIKPLLKSAEREKEMASMKEEFTR                   LKEALEKSEARRKELEEKMVSLLQEKNILQIQVQAEQDNLADAEERCDQLIKNKIQLEAKVKEMNE                   RLEDEEEMNAELTAKKRKLEDECSELKRDIDLELTLAICVEKEKHATENKVKNLTEEMAGLDEIIA                   KLTKEKKALQEAHQQALDDLQAEEDKVNTLTKAKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLE                   GDLKLTQESIMDLENDKQQLDERLKKKDEELNALIARIEDEQALGSQLQIHKLKELQARIELEEEL                   ESERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEAT                   AAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKMCRTLED                   QMNEHRSKAEETQRSVNDLTSQRAKLQTENGELSRQLDEKEALISQLTRGKLTYTQQLEDLKRQLE                   EEVKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETHAIQRTEEL                   EEAKKKLAQRLQEAEEAVEAVNAKCSSLEKTKHRIQNEIEDLMVDVERSNAAAAALDKKQRNFDKI                   LAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGS                   SGKTIHELEKVRKQLEAEKMELQSALEEAEASLEIHEEGKILRAQLENQIKAEIERKLAEKDEEME                   QAKRNIILRVVDSLQTSLDAETRSRNEALRVKKQTERSRKLAEQELIETSERVQLLHSQNTSLINQ                   KKKMDADLSQLQTEVEEAVQECRNAEEKAKKAITDAANMAEELKKEQDTSAILERMKKNMEQTIRD                   LQHRLDEAEQIALKGGKKQLQKLEARVRELENELEAEQKRNAESVKGMRKSERRIKELTYQTEEDR                   KNLLRLQDLDVDKQLKVKAYKRQAEEAEEQANTNLSRFRKVQHELDEAEERADIAESQVNKLRAKS                   RDIGTKGLNEE                                     SEQ NO:21   6008 bp                     NOV4d,     TGTCTTTCCCTGCTGCTCTCAGGTCCCCTGCAGCCCTTGGCCCCTTTCCTCATCTGTAGACACACT         CG120781-02       DNA Sequence     TGAGTAGCCCACGCACAGCC   ATG GGAGATTCGGAGATGGCAGTCTTTGGGGCTGCCGCCCCCTACC                   TGCGCAAGTCAGAGAAGGAGCGCCTAGAAGCGCAGACCACGCCTTTTGACCTCAAGAAGGATGTCT                   TCGTGCCTGATGACAAACAGGAGTTTGTCAACGCCAAGATCGTGTCTCGAGAGGGTGGCAAAGTCA                   CTGCCGAGACTGAGTATGGCAAGACAGTGACCGTGAAGGAGGACCAGGTGATGCAGCAGAACCCAC                   CCAAGTTCGACAAAATCGAGGACATGGCCATGCTGACCTTCCTGCATGAGCCCGCGGTGCTCTACA                   ACCTCAAGGATCGCTACGGCTCCTGGATGATCTACACCTACTCGGGCCTCTTCTGTGTCACCGTCA                   ACCCTTACAAGTGGCTGCCGGTGTACACTCCTGAGGTGGTGGCTGCCTACCGGGGCAAGAAGAGGA                   GCGAGGCCCCGCCCCACATCTTCTCCATCTCCGACAACGCCTATCAGTACATGCTGACAGACAGAG                   AAAACCAGTCCATCCTGATCACCGGAGAATCCGGAGCAGGGAAGACAGTCAACACCAAGAGGGTCA                   TCCAGTACTTTGCTGTTATTGCAGCCATTGGGGACCGCAGCAAGAAGGACCAGAGCCCGGCCAAGG                   GCACCCTGGAGGACCAGATCATCCAGGCCAACCCTGCTCTGGACGCCTTTGGCAATCCCAAGACCG                   TCCGGAACGACAACTCCTCCCGCTTCGGGAAATTCATTCCAATTCATTTTGGGGCAACAGGAAAGT                   TGGCATCTGCAGACATAGAGACCTATCTTCTGGAAAAATCCAGAGTTATTTTCCAGCTGAAAGCAG                   AGAGAGATTATCACATTTTCTACCAAATCCTGTCTAACAAAAAGCCTGAGCTGCTGGACATGCTGC                   TGATCACCAACAACCCCTACGATTATGCATTCATCTCCCAAGGAGAGACCACCGTGGCCTCCATTG                   ATGACGCTGAGGAGCTCATGGCCACTGATAACGCTTTTGATGTGCTGGGCTTCACTTCAGAGGAGA                   AAAACTCCATGTATAAGCTGACAGGCGCCATCATGCACTTTGGAAACATGAAGTTCAAGCTGAAGC                   AGCGGGACGAGCACGCCGAGCCAGACCGCACTGAAGAGGCTGACAAGTCTGCCTACCTCATGGGGC                   TGAACTCAGCCGACCTGCTCAAGGGGCTGTGCCACCCTCGGGTGAAAGTGGGCAATGAGTACGTCA                   CCAAGGGGCAGAATGTCCAGCAGGTGATATATGCCACTGGGGCACTGGCCAAGGCAGTGTATGAGA                   GGATGTTCAACTGGATGGTGACGCGCATCAATGCCACCCTGGAGACCAAGCAGCCACGCCAGTACT                   TCATAGGAGTCCTGGACATCGCTGGCTTCGAGATCTTCGATTTCAACAGCTTTGAGCAGCTCTGCA                   TCAACTTCACCAACGAGAAGCTGCAGCAGTTCTTCAACCACCACATGTTTGTGCTGGAGCAGGAGG                   AGTACAAGAAGGAGGGCATCGAGTGGACATTCATTGACTTTGGCATGGACCTGCAGGCCTGCATTG                   ACCTCATCGAGAAGCCCATGGGCATCATGTCCATCCTGGAAGAGGAGTGCATGTTCCCCAAGGCCA                   CCGACATGACCTTCAAGGCCAAGCTGTTTGACAACCACCTGGGCAAATCCGCCAACTTCCAGAAGC                   CACGAAATATCAAGGGGAAGCCTGAAGCCCACTTCTCCCTGATCCACTATGCCGGCATCGTGGACT                   ACAACATCATTGGCTGGCTGCAGAAGAACAAGGATCCTCTCAATGAGACTGTCGTGGGCTTGTATC                   AGAAGTCTTCCCTCAAGTTGCTCAGCACCCTGTTTCCCAACTATGCTGGGGCTGATGCGCCTATTG                   AGAAGGGCAAAGGCAAGGCCAAGAAAGGCTCGTCCTTTCAGACTGTGTCAGCTCTGCACAGGGAAA                   ATCTGAACAAGCTGATGACCAACTTGCGCTCCACCCATCCCCACTTTGTACGTTGTATCATCCCTA                   ATGAGACAAAGTCTCCAGGCGTGATGGACAACCCCCTGGTCATGCACCAGCTGCGCTGCAATGGTG                   TGCTGGAGGGCATCCGCATCTGCAGGAAAGGCTTCCCCAACCGCATCCTCTACGGGGACTTCCGGC                   AGAGGTATCGCATCCTGAACCCAGCGGCCATCCCTGAGGGACAGTTCATTGATAGCAGGAAGGGGG                   CAGAGAAGCTGCTCAGCTCCCTGGACATTGATCACAACCAGTACAACTTTGGCCACACCAAGGTGT                   TCTTCAAGGCCGGGCTGCTGGGGCTGCTGGAGGAAATGAGCGACGAGAGGCTGAGCCGCATCATCA                   CGCGTATCCAGGCCCAGTCCCGAGGTGTGCTCGCCAGAATGGAGTACAAAAAGCTGCTGGAACGTA                   GAGACTCCCTGCTGGTAATCCAGTGGAACATTCGGGCCTTCATGGGGGTCAAGAATTCGCCCTCGA                   TGAAGCTCTACTTCAAGATCAAGCCGCTGCTGAAGAGTGCAGAAAGAGAGAAGGAGATGGCCTCCA                   TGAAGGAGGAGTTCACACGCCTCAAAGAGGCGCTAGAGAAGTCCGAGGCTCGCCGCAAGGAGCTGG                   AGGAGAAGATGGTGTCCCTGCTGCAGGAGAAGAATGACCTGCAGCTCCAAGTGCAGGCGGAACAAG                   ACAACCTGGCAGATGCTGAGGAGCGCTGTGATCAGCTGATCAAAAACAAGATTCAGCTGGAGGCTA                   AGGTGAAGGAGATGAACGAGAGGCTGGAGGATGACGAGGAGATGAATGCTGAGCTCACTGCCAAGA                   AGCGCAAGTTGGAAGATGAGTGCTCAGAGCTCAAAAGGGACATCGATGATCTGGAGCTGACACTGG                   CCAAAGTGGAGAAGGAGAAACACGCAACAGAGAACAAGGTGAAAAACCTGACAGAGGAGATGGCTG                   CGCTGGATGAGATCATTGCCAAGCTGACCAAGGAGAAGAAAGCTCTGCAAGAGGCCCACCAACAGG                   CTCTGGATGACCTTCAGGCCGAGGAGGACAAGGTCAACACCCTGACTAAGGCCAAAGTCAAGCTGG                   AGCAGCAAGTGGATGATCTCGAAGGATCCCTGGAGCAAGAGAAGAAGGTGCGCATGGACCTCGAGC                   GAGCGAAGCGGAAGCTGGAGGGCGACCTGAAGCTGACCCAGGAGAGCATCATGGACCTGGAGAATG                   ACAAGCAGCAGCTGGATGAGCGGCTGAAAAAAAAAGACTTTGAGCTGAATGCTCTCAACGCAACGA                   TTGAGGATGAACAGGCCCTCGGCAGCCAGCTGCAGAAGAAGCTCAAGGAGCTTCAGGCACGCATCG                   AGGAGCTGGAGGAGGAGCTGGAGTCCGAGCGCACCGCCAGGGCTAAGGTGGAGAAGCTGCGCTCAG                   ACCTGTCTCGGGAGCTGGAGGAGATCAGCGAGCGGCTCGAAGAGGCCGGCGGGGCCACGTCCGTGC                   AGATCGAGATGAACAAGAAGCGCGAGGCCGAGTTCCAGAAGATGCGGCGGGACCTGGAGGAGGCCA                   CGCTGCAGCACGAGGCCACTGCCGCGGCCCTGCGCAAGAAGCACGCCGACAGCGTGGCCGAGCTCG                   GCGAGCAGATCGACAACCTGCAGCGGGTGAAGCAGAAGCTGCAGAAGGAGAAGAGCGAGTTCAAGC                   TGGAGCTGGATGACGTCACCTCCAACATGGAGCAGATCATCAAGGCCAAGGCTAACCTGGAGAAGA                   TGTGCCGGACCTTGGAAGACCAGATGAATGAGCACCGGAGCAAGGCGGAGGAGACCCAGCGTTCTG                   TCAACGACCTCACCAGCCAGCGGGCCAAGTTGCAAACCGAGAATGGTGAGCTGTCCCGGCAGCTGG                   ATGAGAAGGAGGCACTGATCTCCCAGCTGACCCGAGGCAAGCTCACCTACACCCAGCAGCTGGAGG                   ACCTCAAGAGGCAGCTGGAGGAGGAGGTTAAGGCGAAGAACGCCCTGGCCCACGCACTGCAGTCGG                   CCCGCCATGACTGCGACCTGCTGCGCGAGCAGTACGAGGAGGAGACGGAGGCCAAGGCCGAGCTGC                   AGCGCGTCCTTTCCAAGGCCAACTCGGAGGTGGCCCAGTGGAGGACCAAGTATGAGACCGACGCCA                   TTCAGCGGACTGAGGAGCTCGAGGAGGCCAAGAAGAAGCTGGCCCAGCGGCTGCAGGAAGCTGAGG                   AGGCCGTGGAGGCTGTTAATGCCAAGTGCTCCTCGCTGGAGAAGACCAAGCACCGGCTACAGAATG                   AGATCGACGACTTGATGGTGGACGTAGAGCGCTCCAATGCTGCTCCTGCAGCCCTGGACAAGAAGC                   AGAGGAACTTCGACAAGATCCTGGCCGAGTGGAAGCAGAAGTATGAGGAGTCGCAGTCGGAGCTGG                   AGTCCTCGCAGAAGGAGGCTCGCTCCCTCAGCACAGAGCTCTTCAAACTCAAGAACGCCTATGAGG                   AGTCCCTGGAACATCTGGAGACCTTCAAGCCGGAGAACAAAAACCTGCAGGAGGAGATCTCCGACT                   TGACTGAGCAGTTGGGTTCCAGCGGAAAGACTATCCATGAGCTGGAGAAGGTCCGAAAGCAGCTGG                   AGGCCGAGAAGATGGAGCTGCAGTCAGCCCTGGAGGAGGCCGAGGCCTCCCTGGAGCACGAGGAGG                   GCAAGATCCTCCGGGCCCAGCTGGAGTTCAACCAGATCAAGGCAGAGATCGAGCGGAAGCTGGCAG                   AGAAGGACGAGGAGATGGAACAGGCCAAGCGCAACCACCTGCGGGTGGTGGACTCGCTGCAGACCT                   CCCTGGACGCAGAGACACGCAGCCGCAACGAGGCCCTGAGGGTGAAGAAGAAGATGGAAGGAGACC                   TCAATGAGATGGAGATCCAGCTCAGCCACGCCAACCGCATGGCCCCCGAGGCCCAGAAGCAAGTCA                   AGAGCCTCCAGAGCTTGTTGAAGGACACCCAGATTCAGCTGGACGATGCAGTCCGTGCCAACGACG                   ACCTGAAGGAGAACATCGCCATCGTGGAGCGGCGCAACAACCTGCTGCAGGCTGAGCTCGAGGAGT                   TGCGTGCCGTMGGGGAGCAGACAGAGCGGTCCCGGAAGCTGGCGGAGCAGGAGCTGATTGAGACTA                   GTGAGCGGGTGCAGCTGCTGCATTCCCAGAACACCAGCCTCATCAACCAGAAGAAGAAGATGGATG                   CTGACCTGTCCCAGCTCCACACTGAAGTGGAGGAGGCAGTGCAGGAGTGCAGGAATGCTGACGAGA                   AGGCCAAGAAGGCCATCACGGATGCCGCCATGATGGCAGACGAGCTGAAGAAGGAGCAGGACACCA                   GCGCCCACCTGGAGCGCATGAAGAAGAACATGGAACAGACCATTAAGGACCTGCAGCACCGGCTGG                   ACGAAGCCGAGCAGATCGCCCTCAAGGGCGGCAAGAAGCAGCTGCAGAAGCTGCAAGCGCGGGTGC                   GGGAGCTGGAGAATGAGCTGGAGGCCGAGCAGAAGCGCAACGCAGAGTCGGTGAAGGGCATGAGGA                   AGAGCGAGCGGCGCATCAAGGAGCTCACCTACCAGACGGAGGAGGACAGGAAAAACCTGCTGCGGC                   TGCACGACCTGGTAGACAAGCTGCAGCTAAAGGTCAAGGCCTACAAGCGCCAGGCCGAGGAGGCGG                   AGGAGCAAGCCAACACCAACCTGTCCAAGTTCCGCAAGGTCCACCACGAGCTGGATGAGGCAGAGG                   AGCGGGCGGACATCGCCGAGTCCCAGGTCAACAAGCTGCGGGCCAAGAGCCGTGACATTGGCACGA                   AGGGCTTGAATGAGGAG TAG   CTTTGCCACATCTTGATCTGCTCAGCCCTGGAGCTCCCAGCAAAGC                       CCATGCTGGAGCCTGTGTAACAGCTCCTTGGGAGGAAGCAGAATAAAGCAATTTTCCTTGAAGCC                       GA                                           ORF Start: ATG at 87       ORF Stop: TAG at 5892           SEQ ID NO:22   1935 aa   MW at 223111.0 kD                     NOV4d,   MGDSEMAVFGAAPYLRICSEKERLEAQTRPFDLKKDVFVPDDKQEFVKAKIVSREGGKVTAETEYG       CG120781-02       Protein Sequence   KTVTVKEDQVMQQNPPKFDRIEDMAMLTFLHEPAVLYNLKDRYGSWMIYTYSGLFCVTVNPYKWLP                   VYTPEVVAAYRGKKRSEAPPHIFSISDNAYQYMLTDRENOSILITGESGAGKTVNTKRVIQYFAVI                   AAIGDRSKKDQSPGKGTLEDQIIQANPALEAFGNAKTVRNONSSRFGKFIRIHFGATGKLASADIE                   TYLLEKSRVIFQLKAERDYHIFYQILSNKKPELLDMLLITNNPYDYAFISQGETTVASIDDAEELM                   ATDNAFDVLGFTSEEKNSMYKLTGAIMHFGINKFKLKQREEQAEPDGTEEADKSAYLMGLNSADLL                   KGLCHPRVKVGMEYVTKGQNVQQVIYATGALAKAVYERMFNWMVTRINATLETKQPRQYFIGVLDI                   AGFEIFDFNSFEQLCINFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIOFGMDLQACIDLIEKPM                   GIMSILEEECMPPKATDMTFKAKLFONIILGKSANFQKPRNIKGKPEAHFSLIHYAGIVDYNIGWL                   QKNKDPLNETVVGLYQKSSLKLLSTLFANYAGADAPIEKGKGKAKKGSSFQTVSALHRENIMKLMT                   NLRSTHPHFVRCIIPNETKSPGVMDNPLVMHQLRCNOVLEGIRICRKGFPNRTLYGGERQRYRILN                   PAAIPEGQFIDSRKGAEKLLSSLDIDHNQYKFGHTKVFPKAGLLGLLEEMRDERLSRIITRIQAQS                   RGVLARMEYKKLLERRDSLLVIQWNIRAFMGVKNWPWMKLYFKIKPLLKSAEREKEMASMKEEFTR                   LKEALEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLADAEERCGQLIKNKTQLEAKVKEMNE                   RLEDEEEMNAELTAKKRKLEDECSELKRDIDDLELTLAKVEKEKHATENKVKNLTEEMAGLDEIIA                   KLTKEKKALQEAHQQALDDLQAEEDKVNTLTKAKVKLEOQVDDLEGSLEQEKKVRMDLERAKRKLE                   GDLKLTQESIMDLENDKQQLDERLKKKDFELNALNARIEDEQALGSQLQKKLKELQARIESLEFEL                   ESERTARAKVEKLRSDLSRELEEISERLEEAGGATSVQIEMMKKREAEFQKMRRDLEEATLQHEAT                   AAALRKKHADSVAELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKMCRTLED                   QMNEHRSKAEETQRSVNDLTSQRAKLQTENGELSRQLDEKEALISQLTRGKLTYTQQLEDLKRQLE                   EEVKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAIQRTEEL                   EEAKKKLAQRLQEAEEAVEAVNAKCSSLEKTKHRLQNETEDLMVDVERSNAAAAALDKKORNFDKI                   LAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKRENKNLQEEISDLTEQLGS                   SGKTIHELEKVRKQLEAEKMELOSALEEAEASLEHEEGKILRAQLEFNQTKAEIERKLAEKDEEME                   QAKRNHLRVVDSLQTSLDAETRSRNEALRVKKKMEGDLNEMEIQLSHANRMAAEAQKQVKSLQSLL                   KDTQIQLDGAVRANDDLKENIAIVERRNNLLQAELEELRAVVEQTERSRKLAEQELIETSERVQLL                   HSQNTSLINQKKKMDADLSQLQTEVEEAVQECRNAEEKAKKAITDAANMAEELKKEQDTSAHLERM                   KKNNEQTIKDLQHRLDEAEQIALKGGKKQLQKLEARVRELENELEAEQKRNAESVKGMRKSERRIK                   ELTYQTEEDRKNLLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERAIHAE                   SQVNKLRAKSRDIGTKGLNEE                  
 
     [0376] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 4B.  
               TABLE 4B                          Comparison of NOV4a against NOV4b through NOV4d.                                         Identities/                   Similarities for           Protein   NOV4a Residues/   the Matched           Sequence   Match Residues   Region                       NOV4b   397 . . . 1137    460/741 (62%)               841 . . . 1524    540/741 (72%)           NOV4c    1 . . . 1137   1002/1137 (88%)               799 . . . 1859   1026/1137 (90%)           NOV4d    1 . . . 1137   1133/1137 (99%)               799 . . . 1935   1137/1137 (99%)                      
 
     [0377] Further analysis of the NOV4a protein yielded the following properties shown in Table 4C.  
               TABLE 4C                       Protein Sequence Properties NOV4a                                        SignalP analysis:   No Known Signal Sequence Predicted                         PSORT II analysis:   PSG:   a new signal peptide prediction method                                             N-region:   length 11;   pos. chg 4;   neg. chg 3               H-region:   length 9;   peak value   3.86               PSG score:   −0.54                             GvH:   von Heijne&#39;s method for signal seq. recognition                                     GvH score (threshold: −2.1):   −8.01               possible cleavage site:   between 24 and 25                         &gt;&gt;&gt; Seems to have no N-terminal signal peptide                             ALOM:   Klein et al&#39;s method for TM region allocation               Init position for calculation: 1               Tentative number of TMS(s) for the threshold 0.5: 0               number of TMS(s) . . . fixed               PERIPHERAL Likelihood = 8.70 (at 11)               ALOM score: 8.70 (number of TMSs : 0)           MITDISC:   discrimination of mitochondrial targeting seq                                             R content:     0   Hyd Moment (75):   8.33               Hyd Moment (95):     7.86   G content:   0               D/E content:     2   S/T content:   0               Score:   −6.54                             Gavel:   prediction of cleavage sites for mitochondrial preseq               cleavage site motif not found           NUCDISC:   discrimination of nuclear localization signals                                     pat4:   KKRK (5) at 141               pat4:   RKKH (3) at 395               pat7:   none               bipartite:   none               content of basic residues:   18.6%               NLS Score:    0.03                             KDEL: ER retention motif in the C-terminus:   none           ER Membrane Retention Signals:   none           SKL: peroxisomal targeting signal in the C-terminus:   none           PTS2: 2nd peroxisomal targeting signal:   none           VAC: possible vacuolar targeting motif:   none           RNA-binding motif:   none           Actinin-type actin-binding motif:                                 type 1: none               type 2: none                             NMYR: N-myristoylation pattern:   none           Prenylation motif:   none           memYQRL: transport motif from cell surface to Golgi:   none           Tyrosines in the tail:   none           Dileucine motif in the tail:   none           checking 63 PROSITE DNA binding motifs:                                 Leucine zipper pattern (PS00029): *** found ***                LTAKKRKLEDECSELKRDIDDL at 138                LTEEMAGLDEIIAKLTKEKKAL at 180           none                             checking 71 PROSITE ribosomal protein motifs:   none           checking 33 PROSITE prokaryotic DNA binding motifs:   none                         NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination                                     Prediction:   nuclear               Reliability:   94.1                             COIL:   Lupas&#39;s algorithm to detect coiled-coil regions            40 L     0.57            41 L     0.93            42 K     0.97            43 S     0.97            44 A     0.98            45 E     0.99            46 R     0.99            47 E     1.00            48 K     1.00            49 E     1.00            50 M     1.00            51 A     1.00            52 S     1.00            53 M     1.00            54 K     1.00            55 E     1.00            56 E     1.00            57 F     1.00            58 T     1.00            59 R     1.00            60 L     1.00            61 K     1.00            62 E     1.00            63 A     1.00            64 L     1.00            65 E     1.00            66 K     1.00            67 S     1.00            68 E     1.00            69 A     1.00            70 R     1.00            71 R     1.00            72 K     1.00            73 E     1.00            74 L     1.00            75 E     1.00            76 E     1.00            77 K     1.00            78 M     1.00            79 V     1.00            80 S     1.00            81 L     1.00            82 L     1.00            83 Q     1.00            84 E     1.00            85 K     1.00            86 N     1.00            87 D     1.00            88 L     1.00            89 Q     1.00            90 L     1.00            91 Q     1.00            92 V     1.00            93 Q     1.00            94 A     1.00            95 E     1.00            96 Q     1.00            97 D     1.00            98 N     1.00            99 L     1.00            100 A     1.00            101 D     1.00            102 A     1.00            103 E     1.00            104 E     1.00            105 R     1.00            106 C     1.00            107 D     1.00            108 Q     1.00            109 L     1.00            110 I     1.00            111 K     1.00            112 N     1.00            113 K     1.00            114 I     1.00            115 Q     1.00            116 L     1.00            117 E     1.00            118 A     1.00            119 K     1.00            120 V     1.00            121 K     1.00            122 E     1.00            123 M     1.00            124 N     1.00            125 E     1.00            126 R     1.00            127 L     1.00            128 E     1.00            129 D     1.00            130 E     1.00            131 E     1.00            132 E     1.00            133 M     1.00            134 N     1.00            135 A     1.00            136 E     1.00            137 L     1.00            138 T     1.00            139 A     1.00            140 K     1.00            141 K     1.00            142 R     1.00            143 K     1.00            144 L     1.00            145 E     1.00            146 D     1.00            147 E     1.00            148 C     1.00            149 S     1.00            150 E     1.00            151 L     1.00            152 K     1.00            153 R     1.00            154 D     1.00            155 I     1.00            156 D     1.00            157 D     1.00            158 L     1.00            159 E     1.00            160 L     1.00            161 T     1.00            162 L     1.00            163 A     1.00            164 K     1.00            165 V     1.00            166 E     1.00            167 K     1.00            168 E     1.00            169 K     1.00            170 H     1.00            171 A     1.00            172 T     1.00            173 E     1.00            174 N     1.00            175 K     1.00            176 V     1.00            177 K     1.00            178 N     1.00            179 L     1.00            180 T     1.00            181 E     1.00            182 E     1.00            183 M     1.00            184 A     1.00            185 G     1.00            186 L     1.00            187 D     1.00            188 E     1.00            189 I     1.00            190 I     1.00            191 A     1.00            192 K     1.00            193 L     1.00            194 T     1.00            195 K     1.00            196 E     1.00            197 K     1.00            198 K     1.00            199 A     1.00            200 L     1.00            201 Q     1.00            202 E     1.00            203 A     1.00            204 H     1.00            205 Q     1.00            206 Q     1.00            207 A     1.00            208 L     1.00            209 D     1.00            210 D     1.00            211 L     1.00            212 Q     1.00            213 A     1.00            214 E     1.00            215 E     1.00            216 D     1.00            217 K     1.00            218 V     1.00            219 N     1.00            220 T     1.00            221 L     1.00            222 T     1.00            223 K     1.00            224 A     1.00            225 K     1.00            226 V     1.00            227 K     1.00            228 L     1.00            229 E     1.00            230 Q     1.00            231 Q     1.00            232 V     1.00            233 D     1.00            234 D     1.00            235 L     1.00            236 E     1.00            237 G     1.00            238 S     1.00            239 L     1.00            240 E     1.00            241 Q     1.00            242 E     1.00            243 K     1.00            244 K     1.00            245 V     1.00            246 R     1.00            247 M     1.00            248 D     1.00            249 L     1.00            250 E     1.00            251 R     1.00            252 A     1.00            253 K     1.00            254 R     1.00            255 K     1.00            256 L     1.00            257 E     1.00            258 G     1.00            259 D     1.00            260 L     1.00            261 K     1.00            262 L     1.00            263 T     1.00            264 Q     1.00            265 E     1.00            266 S     1.00            267 I     1.00            268 M     1.00            269 D     1.00            270 L     1.00            271 E     1.00            272 N     1.00            273 D     1.00            274 K     1.00            275 Q     1.00            276 Q     1.00            277 L     1.00            278 E     1.00            279 E     1.00            280 R     1.00            281 L     1.00            282 K     1.00            283 K     1.00            284 K     1.00            285 D     1.00            286 F     1.00            287 E     1.00            288 L     1.00            289 N     1.00            290 A     1.00            291 L     1.00            292 N     1.00            293 A     1.00            294 R     1.00            295 I     1.00            296 E     1.00            297 D     1.00            298 E     1.00            299 Q     1.00            300 A     1.00            301 L     1.00            302 G     1.00            303 S     1.00            304 Q     1.00            305 L     1.00            306 Q     1.00            307 K     1.00            308 K     1.00            309 L     1.00            310 K     1.00            311 E     1.00            312 L     1.00            313 Q     1.00            314 A     1.00            315 R     1.00            316 I     1.00            317 E     1.00            318 E     1.00            319 L     1.00            320 E     1.00            321 E     1.00            322 E     1.00            323 L     1.00            324 E     1.00            325 A     1.00            326 E     1.00            327 R     1.00            328 T     1.00            329 A     1.00            330 R     1.00            331 A     1.00            332 K     1.00            333 V     1.00            334 E     1.00            335 K     1.00            336 L     1.00            337 R     1.00            338 S     1.00            339 D     1.00            340 L     1.00            341 S     1.00            342 R     1.00            343 E     1.00            344 L     1.00            345 E     1.00            346 E     1.00            347 I     1.00            348 S     0.99            349 E     0.99            350 R     0.99            351 L     0.99            352 E     0.99            353 E     0.99            354 A     0.99            355 G     0.96            356 G     0.91            357 A     0.91            358 T     0.72            359 S     0.50            369 E     0.65            370 A     0.65            371 E     0.65            372 F     0.65            373 Q     0.65            374 K     0.65            375 M     0.65            376 R     0.65            377 R     0.65            378 D     0.65            379 L     0.65            380 E     0.65            381 E     0.65            382 A     0.65            383 T     0.65            384 L     0.65            385 Q     0.65            386 H     0.65            387 E     0.65            388 A     0.65            389 T     0.65            390 A     0.65            391 A     0.72            392 A     0.95            393 L     0.97            394 R     1.00            395 K     1.00            396 K     1.00            397 H     1.00            398 A     1.00            399 D     1.00            400 S     1.00            401 V     1.00            402 A     1.00            403 E     1.00            404 L     1.00            405 G     1.00            406 E     1.00            407 Q     1.00            408 I     1.00            409 D     1.00            410 N     1.00            411 L     1.00            412 Q     1.00            413 R     1.00            414 V     1.00            415 K     1.00            416 Q     1.00            417 K     1.00            418 L     1.00            419 E     1.00            420 K     1.00            421 E     1.00            422 K     1.00            423 S     1.00            424 E     1.00            425 F     1.00            426 K     1.00            427 L     1.00            428 E     1.00            429 L     1.00            430 D     1.00            431 D     1.00            432 V     1.00            433 T     1.00            434 S     1.00            435 N     1.00            436 M     1.00            437 E     1.00            438 Q     1.00            439 I     1.00            440 I     1.00            441 K     1.00            442 A     1.00            443 K     1.00            444 A     1.00            445 N     1.00            446 L     1.00            447 E     1.00            448 K     1.00            449 M     1.00            450 C     1.00            451 R     1.00            452 T     1.00            453 L     1.00            454 E     1.00            455 D     1.00            456 Q     1.00            457 M     1.00            458 N     1.00            459 E     1.00            460 H     1.00            461 R     1.00            462 S     1.00            463 K     1.00            464 A     1.00            465 E     1.00            466 E     1.00            467 T     1.00            468 Q     1.00            469 R     1.00            470 S     1.00            471 V     1.00            472 N     1.00            473 D     1.00            474 L     1.00            475 T     1.00            476 S     1.00            477 Q     1.00            478 R     1.00            479 A     1.00            480 K     1.00            481 L     1.00            482 Q     1.00            483 T     1.00            484 E     1.00            485 N     1.00            486 G     1.00            487 E     1.00            488 L     1.00            489 S     1.00            490 R     1.00            491 Q     1.00            492 L     1.00            493 D     0.99            494 E     0.99            495 K     0.99            496 E     0.99            497 A     0.99            498 L     0.99            499 I     0.99            500 S     0.99            501 Q     0.99            502 L     0.99            503 T     0.99            504 R     0.99            505 G     0.99            506 K     0.99            507 L     0.99            508 T     0.99            509 Y     1.00            510 T     1.00            511 Q     1.00            512 Q     1.00            513 L     1.00            514 E     1.00            515 D     1.00            516 L     1.00            517 K     1.00            518 R     1.00            519 Q     1.00            520 L     1.00            521 E     1.00            522 E     1.00            523 E     1.00            524 V     1.00            525 K     1.00            526 A     1.00            527 K     1.00            528 N     1.00            529 A     1.00            530 L     1.00            531 A     1.00            532 H     1.00            533 A     1.00            534 L     1.00            535 Q     1.00            536 S     1.00            537 A     1.00            538 R     1.00            539 H     1.00            540 D     1.00            541 C     1.00            542 D     1.00            543 L     1.00            544 L     1.00            545 R     1.00            546 E     1.00            547 Q     1.00            548 Y     1.00            549 E     1.00            550 E     1.00            551 E     1.00            552 T     1.00            553 E     1.00            554 A     1.00            555 K     1.00            556 A     1.00            557 E     1.00            558 L     1.00            559 Q     1.00            560 R     1.00            561 V     1.00            562 L     1.00            563 S     1.00            564 K     1.00            565 A     1.00            566 N     1.00            567 S     1.00            568 E     1.00            569 V     1.00            570 A     1.00            571 Q     1.00            572 W     1.00            573 R     1.00            574 T     0.99            575 K     0.99            576 Y     0.99            577 E     1.00            578 T     1.00            579 D     1.00            580 A     1.00            581 I     1.00            582 Q     1.00            583 R     1.00            584 T     1.00            585 E     1.00            586 E     1.00            587 L     1.00            588 E     1.00            589 E     1.00            590 A     1.00            591 K     1.00            592 K     1.00            593 K     1.00            594 L     1.00            595 A     1.00            596 Q     1.00            597 R     1.00            598 L     1.00            599 Q     1.00            600 E     1.00            601 A     1.00            602 E     1.00            603 E     1.00            604 A     1.00            605 V     1.00            606 E     1.00            607 A     1.00            608 V     1.00            609 N     1.00            610 A     1.00            611 K     1.00            612 C     1.00            613 S     1.00            614 S     1.00            615 L     1.00            616 E     1.00            617 K     1.00            618 T     1.00            619 K     1.00            620 H     1.00            621 R     1.00            622 L     1.00            623 Q     1.00            624 N     1.00            625 E     1.00            626 I     1.00            627 E     1.00            628 D     1.00            629 L     1.00            630 M     1.00            631 V     0.99            632 D     0.99            633 V     0.99            634 E     0.99            635 R     0.99            636 S     0.98            637 N     0.98            638 A     0.98            639 A     0.98            640 A     0.98            641 A     0.98            642 A     0.98            643 L     0.98            644 D     0.97            645 K     0.97            646 K     0.97            647 Q     0.95            648 R     0.97            649 N     0.97            650 F     0.97            651 D     1.00            652 K     1.00            653 I     1.00            654 L     1.00            655 A     1.00            656 E     1.00            657 W     1.00            658 K     1.00            659 Q     1.00            660 K     1.00            661 Y     1.00            662 E     1.00            663 E     1.00            664 S     1.00            665 Q     1.00            666 S     1.00            667 E     1.00            668 L     1.00            669 E     1.00            670 S     1.00            671 S     1.00            672 Q     1.00            673 K     1.00            674 E     1.00            675 A     1.00            676 R     1.00            677 S     1.00            678 L     1.00            679 S     1.00            680 T     1.00            681 E     1.00            682 L     1.00            683 F     0.99            684 K     1.00            685 L     1.00            686 K     1.00            687 N     1.00            688 A     1.00            689 Y     1.00            690 E     1.00            691 E     1.00            692 S     1.00            693 L     1.00            694 E     1.00            695 H     1.00            696 L     1.00            697 E     1.00            698 T     1.00            699 F     1.00            700 K     1.00            701 R     1.00            702 E     1.00            703 N     1.00            704 K     1.00            705 N     1.00            706 L     1.00            707 Q     1.00            708 E     1.00            709 E     1.00            710 I     1.00            711 S     1.00            712 D     1.00            713 L     1.00            714 T     1.00            715 E     1.00            716 Q     1.00            717 L     1.00            718 G     0.99            719 S     0.99            720 S     0.99            721 G     1.00            722 K     1.00            723 T     1.00            724 I     1.00            725 H     1.00            726 E     1.00            127 L     1.00            728 E     1.00            729 K     1.00            730 V     1.00            731 R     1.00            732 K     1.00            733 Q     1.00            734 L     1.00            735 E     1.00            736 A     1.00            737 E     1.00            738 K     1.00            739 M     1.00            740 E     1.00            741 L     1.00            742 Q     1.00            743 S     1.00            744 A     1.00            745 L     1.00            746 E     1.00            747 E     1.00            748 A     1.00            749 E     1.00            750 A     1.00            751 S     1.00            752 L     1.00            753 E     1.00            754 H     1.00            755 E     1.00            756 E     1.00            757 G     1.00            758 K     1.00            759 I     1.00            760 L     1.00            761 R     1.00            762 A     1.00            763 Q     1.00            764 L     1.00            765 E     1.00            766 F     1.00            767 N     1.00            768 Q     1.00            769 I     1.00            770 K     1.00            771 A     1.00            772 E     1.00            773 I     1.00            774 E     1.00            775 R     0.99            776 K     0.98            111 L     0.98            778 A     0.98            779 E     0.98            780 K     0.98            781 D     0.98            782 E     0.98            783 E     0.98            784 M     0.98            785 E     0.98            786 Q     0.98            787 A     0.98            788 K     0.98            789 R     0.98            790 N     0.98            791 H     0.98            792 L     0.98            793 R     0.96            794 V     0.96            795 V     0.93            796 D     0.93            797 S     0.93            798 L     0.93            799 Q     0.93            800 T     0.93            801 S     0.93            802 L     0.96            803 D     0.96            804 A     0.96            805 E     0.96            806 T     0.96            807 R     0.96            808 S     0.96            809 R     0.96            810 N     0.98            811 E     0.98            812 A     0.98            813 L     0.98            814 R     1.00            815 V     1.00            816 K     1.00            817 K     1.00            818 K     1.00            819 M     1.00            820 E     1.00            821 G     1.00            822 D     1.00            823 L     1.00            824 N     1.00            825 E     1.00            826 M     1.00            827 E     1.00            828 I     1.00            829 Q     1.00            830 L     1.00            831 S     1.00            832 H     1.00            833 A     1.00            834 N     1.00            835 R     1.00            836 M     1.00            837 A     1.00            838 A     1.00            839 E     1.00            840 A     1.00            841 Q     1.00            842 K     1.00            843 Q     1.00            844 V     1.00            845 K     1.00            846 S     1.00            847 L     1.00            848 Q     1.00            849 S     1.00            850 L     1.00            851 L     1.00            852 K     1.00            853 D     1.00            854 T     1.00            855 Q     1.00            856 I     1.00            857 Q     1.00            858 L     1.00            859 D     1.00            860 D     1.00            861 A     1.00            862 V     1.00            863 R     1.00            864 A     1.00            865 N     1.00            866 D     1.00            867 D     1.00            868 L     1.00            869 K     1.00            870 E     1.00            871 N     1.00            872 I     1.00            873 A     1.00            874 I     1.00            875 V     1.00            876 E     1.00            877 R     1.00            878 R     1.00            879 N     1.00            880 N     1.00            881 L     1.00            882 L     1.00            883 Q     1.00            884 A     1.00            885 E     1.00            886 L     1.00            887 E     1.00            888 E     1.00            889 L     1.00            890 R     1.00            891 A     1.00            892 V     1.00            893 V     1.00            894 E     1.00            895 Q     1.00            896 T     1.00            897 E     1.00            898 R     1.00            899 S     1.00            900 R     1.00            901 K     1.00            902 L     1.00            903 A     1.00            904 D     1.00            905 E     1.00            906 E     1.00            907 L     1.00            908 I     1.00            909 E     1.00            910 T     0.98            911 S     0.95            912 E     0.95            913 R     0.92            914 V     0.90            915 Q     0.90            916 L     0.90            917 L     0.99            918 H     0.99            919 S     0.99            920 Q     0.99            921 N     0.99            922 T     0.99            923 S     0.99            924 L     1.00            925 I     1.00            926 N     1.00            927 Q     1.00            928 K     1.00            929 K     1.00            930 K     1.00            931 M     1.00            932 D     1.00            933 A     1.00            934 D     1.00            935 L     1.00            936 S     1.00            937 Q     1.00            938 L     1.00            939 Q     1.00            940 T     1.00            941 E     1.00            942 V     1.00            943 E     1.00            944 E     1.00            945 A     1.00            946 V     1.00            947 Q     1.00            948 E     1.00            949 C     1.00            950 R     1.00            951 N     1.00            952 A     1.00            953 E     1.00            954 E     1.00            955 K     1.00            956 A     1.00            957 K     1.00            958 K     1.00            959 A     1.00            960 I     1.00            961 T     1.00            962 D     1.00            963 A     1.00            964 A     1.00            965 M     1.00            966 M     1.00            967 A     1.00            968 E     1.00            969 E     1.00            970 L     1.00            971 K     1.00            972 K     1.00            973 E     1.00            974 Q     1.00            975 D     1.00            976 T     1.00            977 S     1.00            978 A     1.00            979 H     1.00            980 L     1.00            981 E     1.00            982 R     1.00            983 M     1.00            984 K     1.00            985 K     1.00            986 N     1.00            987 M     1.00            988 E     1.00            989 Q     1.00            990 T     1.00            991 I     1.00            992 K     1.00            993 D     1.00            994 L     1.00            995 Q     1.00            996 H     1.00            997 R     1.00            998 L     1.00            999 D     1.00           1000 E     1.00           1001 A     1.00           1002 E     1.00           1003 Q     1.00           1004 I     1.00           1005 A     1.00           1006 L     1.00           1007 K     1.00           1008 G     1.00           1009 G     1.00           1010 K     1.00           1011 K     1.00           1012 Q     1.00           1013 L     1.00           1014 Q     1.00           1015 K     1.00           1016 L     1.00           1017 E     1.00           1018 A     1.00           1019 R     1.00           1020 V     1.00           1021 R     1.00           1022 E     1.00           1023 L     1.00           1024 E     1.00           1025 N     1.00           1026 E     1.00           1027 L     1.00           1028 E     1.00           1029 A     1.00           1030 E     1.00           1031 Q     1.00           1032 K     1.00           1033 R     1.00           1034 N     1.00           1035 A     1.00           1036 E     1.00           1037 S     1.00           1038 V     1.00           1039 K     1.00           1040 G     1.00           1041 M     1.00           1042 R     1.00           1043 K     1.00           1044 S     1.00           1045 E     1.00           1046 R     1.00           1047 R     1.00           1048 I     1.00           1049 K     1.00           1050 E     1.00           1051 L     1.00           1052 T     0.99           1053 Y     0.99           1054 Q     0.99           1055 T     0.99           1056 E     1.00           1057 E     1.00           1058 D     1.00           1059 R     1.00           1060 K     1.00           1061 N     1.00           1062 L     1.00           1063 L     1.00           1064 R     1.00           1065 L     1.00           1066 Q     1.00           1067 D     1.00           1068 L     1.00           1069 V     1.00           1070 D     1.00           1071 K     1.00           1072 L     1.00           1073 Q     1.00           1074 L     1.00           1075 K     1.00           1076 V     1.00           1077 K     1.00           1078 A     1.00           1079 Y     1.00           1080 K     1.00           1081 R     1.00           1082 Q     1.00           1083 A     1.00           1084 E     1.00           1085 E     1.00           1086 A     1.00           1087 E     1.00           1088 E     1.00           1089 Q     1.00           1090 A     1.00           1091 N     1.00           1092 T     1.00           1093 N     1.00           1094 L     1.00           1095 S     1.00           1096 K     1.00           1097 F     1.00           1098 R     1.00           1099 K     1.00           1100 V     1.00           1101 Q     1.00           1102 H     1.00           1103 E     1.00           1104 L     1.00           1105 D     1.00           1106 E     1.00           1107 A     1.00           1108 E     1.00           1109 E     1.00           1110 R     1.00           1111 A     1.00           1112 D     1.00           1113 I     1.00           1114 A     1.00           1115 E     1.00           1116 S     1.00           1117 Q     1.00           1118 V     1.00           1119 N     1.00           1120 K     1.00           1121 L     1.00           1122 R     1.00           1123 A     1.00           1124 K     1.00           1125 S     1.00           1126 R     1.00           1127 D     1.00           1128 I     1.00           1129 G     1.00           1130 T     1.00           1131 K     1.00           1132 G     0.85           total:   1084 residues                         Final Results (k = 9/23):                                     65.2%:   nuclear               21.7%:   cytoplasmic                4.3%:   cytoskeletal                4.3%:   mitochondrial                4.3%:   peroxisomal                         &gt;&gt; prediction for CG120781-01 is nuc (k = 23)                      
 
     [0378] A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4D.  
               TABLE 4D                          Geneseq Results for NOV4a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV4a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value                                         ABG31649   Amino acid distribution analysis   1 . . . 1137   1122/1137 (98%)   0.0           method associated protein -   799 . . . 1935    1127/1137 (98%)           Unidentified, 1935 aa.           [JP2002215635-A, 2 AUG. 2002]       ABB77096   Human alpha-myosin heavy chain -   1 . . . 1132   1071/1132 (94%)   0.0             Homo sapiens , 1939 aa.   801 . . . 1932    1106/1132 (97%)           [US6358751-B1, 19 MAR. 2002]       AAW54241     Rattus norvegicus  mutant   1 . . . 1132   1063/1132 (93%)   0.0           alpha-myosin heavy chain -  Rattus     748 . . . 1879    1104/1132 (96%)             norvegicus , 1886 aa.           [WO9813476-A1, 2 APR. 1998]       ABG21233   Novel human diagnostic protein   1 . . . 1137    906/1143 (79%)   0.0           #21224 -  Homo sapiens , 1948 aa.   806 . . . 1948    1039/1143 (90%)           [WO200175067-A2, 11 OCT. 2001]       ABG79661   Invertebrate foraging behaviour   1 . . . 1128    885/1128 (78%)   0.0           associated human protein #5 -  Homo     800 . . . 1927    1027/1128 (90%)             sapiens , 1940 aa.           [WO200259370-A2, 1 AUG. 2002]                  
 
     [0379] In a BLAST search of public sequence databases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4E.  
               TABLE 4E                          Public BLASTP Results for NOV4a                                             Identities/           Protein           Similarities for       Accession       NOV4a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value                                         P12883   Myosin heavy chain, cardiac muscle   1 . . . 1137   1133/1137 (99%)   0.0           beta isoform (MyHC-beta) -  Homo      799 . . . 1935    1137/1137 (99%)             sapiens  (Human), 1935 aa.       Q9H1D5   Beta-myosin heavy chain -  Homo     1 . . . 1137   1133/1137 (99%)   0.0             sapiens  (Human), 1935 aa.   799 . . . 1935    1136/1137 (99%)       Q8MJU9   Myosin heavy chain slow -  Equus     1 . . . 1137   1121/1137 (98%)   0.0             caballus  (Horse), 1935 aa.   799 . . . 1935    1132/1137 (98%)       Q9GKR1   Myosin heavy chain slow isoform -   1 . . . 1137   1122/1137 (98%)   0.0             Sus scrofa  (Pig), 1935 aa.   799 . . . 1935    1132/1137 (98%)       Q91Z83   Beta myosin heavy chain -  Mus     1 . . . 1137   1118/1137 (98%)   0.0             musculus  (Mouse), 1935 aa.   799 . . . 1935    1132/1137 (99%)                  
 
     [0380] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4F.  
               TABLE 4F                          Domain Analysis of NOV4a                                             Identities/                       Similarities for           Pfam   NOV4a   the Matched   Expect           Domain   Match Region   Region   Value                                                 Myosin_tail   211 . . . 268   21/58 (36%)   0.69                   38/58 (66%)           Myosin_tail    270 . . . 1129   531/864 (61%)    0                   812/864 (94%)                       
 
     Example 5.  
     [0381] 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:23   3657 bp                     NOV5a,     GAGTCCCAGCCCCACGCCGGCTACCACC   ATG GCGGAGACCAACAACGAATGTAGCATCAAGGTGCT       CG122634-01       DNA Sequence   CTGCCGATTCCGGCCCCTGAACCAGGCTGAGATTCTCCCGGGAGACAAGTTCATCCCCATTTTCCA                   AGCGGACGACAGCGTCGTTATTGGGGGGAAGCCATATGTTTTTGACCGTGTATTCCCCCCAAACAC                   GACTCAAGAGCAAGTTTATCATGCATGTGCCATGCAGATTGTCAAAGATGTCCTTGCTGGCTACAA                   TGCCACCATTTTTGCTTATGGACAGACATCCTCAGGGAAAACACATACCATGGACGGAAAGCTGCA                   CGACCCTCAGCTGATGGGAATCATTCCTCGAATTGCCCGAGACATCTTCAACCACATCTACTCCAT                   GGATGAGAACCTTGAGTTCCACATCAAGGTTTCTTACTTTGAAATTTACCTGGACAAAATTCGTGA                   CCTTCTGGATGTCACCAAGACAAATCTGTCCGTGCACGAGGACAAGAACCGGGTGCCATTTGTCAA                   GGGTTGTACTGAACGCTTTGTGTCCAGCCCGGAGGAGATTCTGGATGTGATTGATGAAGGGAAATC                   AAATCGTCATGTGGCTGTCACCAACATGAATGAACACAGCTCTCGGAGCCACACCATCTTCCTCAT                   AACATCAAGCAGGAGAACATGGAAACGGAGCAGAAGCTCAAATGCGAAGCTGTATCTGGTGGACCT                   GGCAGGGAGTGAGAAGGTCAGCAAGACTGGAGCACAGGGAGCCGTGCTGGACGAGGCAAAGAATAT                   CAACAAGTCACTGTCAGCTCTGCGCAATGTGATCTCCGCACTGGCTGAGGGCACTAAAAGCTATGT                   TCCATATCGTGACAGCAAAATGACAAGGATTCTCCAGGACTCTCTCGGGGGAAACTGCCGGACGAC                   TATGTTCATCTGTTGCTCACCATCCAGTTATAATGATGCAGAGACCAAGTCCACCCTGATCTTTCG                   GCAGCGGGCAAAGACCATTAAGAACACTGCCTCAGTAAATTTCGAGTTGACTGCTGAGCAGTGGAA                   GAAGAAATATGAGAAGGAGAAGGAGAAGACAAAGGCCCAGAAGGAGACGATTGCGAAGCTGGAGGC                   TGAGCTGAGCCGGTGGCGCAATGGACAGAATGTGCCTGAGACAGAGCGCCTGGCTGAGGAGGAGGC                   AGCCCTGGGAGCCGAGCTCTGTGAGGAGACCCCTGTGAATGACAACTCATCCATCGTGGTGCGCAT                   CGCGCCCGAGGAGCGGCAGAAATACGAGGAGCAGATCCGCCGTCTCTATAAGCAGCTTGACGACAA                   GGATGATGAAATCAACCAACAAAGCCAACTCATAGAGAAGCTCAAGCAGCAAATGCTGGACCAGGA                   AGAGCTGCTGGTGTCCACCCGAGGAGACAACGAGAAGGTCCAGCGGGAGCTGAGCCACCTGCAATC                   AGAGAACGATGCCGCTAAGGATGAGGTGAAGGAAGTGCTGCACGCCCTGGAGGAGCTGGCTGTGAA                   CTATGACCAGAAGTCCCACGAGGTGGAGGAGAAGAGCCAGCAGAACCAGCTTCTGGTGGATGAGCT                   GTCTCAGAACGTGGCCACCATGCTGTCCCTGGAGTCTGAGTTGCAGCGGCTACAGGAGGTCAGTGG                   ACACCAGCGAAAACGAATTGCTGAGGTGCTGAACGGGCTGATGAAGGATCTGAGCGAGTTCAGTGT                   CATTGTGGGCAACGGGGAGATTAAGCTGCCAGTGGAGATCAGTGGGGCCATCCAGGAGGACTTCAC                   TGTGCCCCGACTCTACATCAGCAAAATCAAATCAGAAGTCAAGTCTGTGGTCAAGCGGTGCCGGCA                   GCTGGAGAACCTCCACGTGGAGTGTCACCGCAAGATGGAAGTGACCGGGCGGGAGCTCTCATCCTG                   CCAGCTCCTCATCTCTCAGCATGAGGCCAAGATCCGCTCGCTTACGGAATACATGCAGAGCGTGGA                   GCTAAAGAAGCCGCACCTGGAAGAGTCCTATGACTCCTTGAGCGATGAGCTGGCCAAGCTCCAGGC                   CCAGGAAACTGTGCATGAAGTGGCCCTGAAGGACAAGGAGCCTGACACTCAGGATGCAGATGAAGT                   GAAGAAGGCTCTGGAGCTGCAGATCGAGAGTCACCGGGAGGCCCATCACCCGCAGCTGGCCCGGCT                   CCGGGACGAGATCAACGAGAAGCAGAAGACCATTGATGAGCTCAAAGACCTAAATCAGAAGCTCCA                   GTTAGAGCTAGAGAAGCTTCAGGCTGACTACGAGAAGCTGAAGAGCGAAGAACACGAGAAGAGCAC                   CAAGCTGCACGAGCTGACATTTCTGTACGAGCGACATGAGCAGTCCAAGCAGGACCTCAAGGGTCT                   GGAGGAGACAGTTGCCCGGGAACTCCAGACCCTCCACAACCTTCGCAAGCTGTTCGTTCAAGACGT                   CACGACTCGAGTCAACAAAAGTGCAGAAATGGAGCCCGAAGACAGTGGGGGGATTCACTCCCAAAA                   GCAGAAGATTTCCTTTCTTGAGAACAACCTGGAACAGCTTACAAAGGTTCACAAACACCTGGTACG                   TGACAATGCAGATCTGCGTTGTGAGCTTCCTAAATTGGAAAAACGACTTAGGGCTACGGCTGACAG                   AGTTAAGGCCCTGGAGGGTGCACTGAAGGAGGCCGTTCGCTACAAGAGCTCGGGCAAACGGGGCCA                   TTCTGCCCAGATTGCCAAACCCGTCCGGCCTGGCCACTACCCAGCATCCTCACCCACCAACCCCTA                   TGGCACCCGGAGCCCTGAGTGCATCAGTTACACCAACAGCCTCTTCCAGAACTACCAGAATCTCTA                   CCTGCAGGCCACACCCAGCTCCACCTCAGATATGTACTTTGCAAACTCCTGTACCAGCAGTGGAGC                   ACATCTTCTGGCGGCCCCTTGGCTTCCTACCAGAAGGCCAACATCGGACAATGGAAATGCCACAGA                   TATCAATGACAATAGGAGTGACCTGCCGTGTGGCTATGAGGCTGAGGACCAGGCCAAGCTTTTCCC                   TCTCCACCAAGAGACAGCAGCCAGC TAA   TCTCCCACACCCACGGCTGCATACCTGCACTTTCAGTT                       TCTAAGAGGGACTGAGGCCTCTTCTCAGCATGCTGCAAACCTGTGGTCTCTGATACTAACTCCCTC                       CCCAACCCCTGTTGTTGGACTGTACTATGTTTGATGTCTTCTCTTACTTACTCTGTATCTCTTTGT                       ACTCTGTATCTATATATCAAAAGCTGCTCCTATGTCTCTCTTCTGTCTTATTCTCAAGTATCTACT                       GATGTATTTAGCAATTTCAAAGCATAGTCTACCTTCCTTATTTGGGGCAATAGGGAGGAGGGTGAA                       TGTTTCTTCTTTCTCATCTACTCGTCTCACACTGAGTGGTGTTAGTCACTGAGTAGAGGTCACAGA                       GATGACAAAACGAAAAATGGGAGCTAGAGGGTTGTGACCCTTCATACACACACGCACACACGCACA                       CAAACATGCACACACGCATGCACACACACAAAGCCTTAAGCAGAAGAATGTCTTAGCATCATGAGA                       CGAGAAATAGACTCTTCCTCCCTCCTCTTTCACATATAGCACAGAACGTAAAATGGAAGGGCTGCT                       AATTGAGACATATAATTTTCGGAATTC                                           ORF Start: ATG at 29       ORF Stop: TAA at 3062           SEQ ID NO:24   1011 aa   MW at 114816.1 kD                      NOV5a,   MAETNNECSIKVLCRFRPLNQAEILRGOKPIPIFQGDDSVVIGGKPYVFDRVFPPNTTQEQVYHAC       CG122634-01       Protein Sequence   AMQIVKDVLAGYNGTIFAYGQTSSGKTHTMECKLHDPQLMGIIPRIARDIFIHIYSMDENLEFHIK                   VSYFEIYLDKIRDLLDVTKTNLSVHEDKNRVPFVKGCTERFVSSPREILDVIDEGKSNRHVAVTNM                   NEHSSRSHSIFLINIKQENMETEQKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKMINKSLSALCN                   VISALAEGTKSYVPYRDSKMTRILQDSLGGNCRTTMFICCSPSSYNDAETKSTLMFGQRAKTIKNT                   ASVNLELTAEQWKKKYEKEKEKTKAQKETIAKLEAELSRWRNGEWVPETERLAGEEAALGAELCEE                   TPVNDNSSIVVRIAPEERQKYEEEIRRLYKQLDDKDDEINQQSQLIEKLKQQMLDQEELLVSTRGD                   NEKVQRELSHLQSENDAAKDEVKEVLQALEELAVNYDQKSQEVEEKSQQNQLLVDELSQKVATMLS                   LESELQRLQEVSGHQRKRIAEVLNGLMKDLSEFSVIVGMGEIKLPVEISGAIEEEFTVARLYISRI                   KSEVKSVVKRCRQLENLQVECHRKMEVTGRELSSCQLLISQHEAKIRSLTEYMQSVELKKRHLEES                   YDSLSDELAKLQAQETVHEVALKDKEPDTQDADEVRKALELQMESHREAHHRQLARLRDEINEKQR                   TIDELKDLNQKLQLELEKLQADYEKLKSEEHEKSTKLQELTFLYERHEQSKQDLKGLEETVARELQ                   TLHNLRKLFVQDVTTRVKKSAEMEPEDSGGIHSQKQKISFLENNLEQLTKVHRQLVRDNADLRCEL                   PKLEKRLRATAERVKALEGALKEAVRYKSSGKRGHSAQIAKPVRPGHYPASSPTRPYGTRSPECIS                   YTNSLFQNYQNLYLGATPSSTSDMYFANSCTSSGATSSGGPLASYQRANMDNGNATDINDNRSDLP                   GYEAEDQAKLFPLHQETAAS                  
 
     [0382] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B.  
               TABLE 5B                       Protein Sequence Properties NOV5a                                        SignalP analysis:   No Known Signal Sequence Predicted       PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 11; pos. chg 1; neg. chg 2           H-region: length 3; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −6.86           possible cleavage site: between 21 and 22           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 5.57 (at 550)           ALOM score: 5.57 (number of TMSs: 0)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   0   Hyd Moment(75):   4.81           Hyd Moment(95):   8.50   G content:   0           D/E content:   2   S/T content:   1                             Score: −6.65                             Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: KKRH (3) at 653           pat7: none           bipartite: none           content of basic residues: 13.7%           NLS Score: −0.29           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs:           Leucine zipper pattern (PS00029): *** found ***           LKDLNQKLQLELEKLQADYEKL at 731           LENNLEQLTKVHKQLVRDNADL at 833           none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: nuclear           Reliability: 89           COIL: Lupas&#39;s algorithm to detect coiled-coil regions                                     330 A   0.63                   331 S   0.63           332 V   0.90           333 N   0.97           334 L   0.98           335 E   0.98           336 L   0.98           337 T   0.99           338 A   1.00           339 E   1.00           340 Q   1.00           341 W   1.00           342 K   1.00           343 K   1.00           344 K   1.00           345 Y   1.00           346 E   1.00           347 K   1.00           348 E   1.00           349 K   1.00           350 E   1.00           351 K   1.00           352 T   1.00           353 K   1.00           354 A   1.00           355 Q   1.00           356 K   1.00           357 E   1.00           358 T   1.00           359 I   1.00           360 A   1.00           361 K   1.00           362 L   1.00           363 E   1.00           364 A   1.00           365 E   1.00           366 L   1.00           367 S   1.00           368 R   0.99           369 W   0.99           370 R   0.99           371 N   0.99           372 G   0.87           373 E   0.55           411 E   0.99           412 E   0.99           413 R   0.99           414 Q   0.99           415 K   0.99           416 Y   0.99           417 E   1.00           418 E   1.00           419 E   1.00           420 I   1.00           421 R   1.00           422 R   1.00           423 L   1.00           424 Y   1.00           425 K   1.00           426 Q   1.00           427 L   1.00           428 D   1.00           429 D   1.00           430 K   1.00           431 D   1.00           432 D   1.00           433 E   1.00           434 I   1.00           435 N   1.00           436 Q   1.00           437 Q   1.00           438 S   1.00           439 Q   1.00           440 L   1.00           441 I   1.00           442 E   1.00           443 K   1.00           444 L   1.00           445 K   0.99           446 Q   0.99           447 Q   0.99           448 M   0.99           449 L   0.99           450 D   0.99           451 Q   0.99           452 E   0.99           453 E   0.99           454 L   0.98           455 L   0.98           456 V   0.98           457 S   0.99           458 T   1.00           459 R   1.00           460 G   1.00           461 D   1.00           462 N   1.00           463 E   1.00           464 K   1.00           465 V   1.00           466 Q   1.00           467 R   1.00           468 E   1.00           469 L   1.00           470 S   1.00           471 H   1.00           472 L   1.00           473 Q   1.00           474 S   1.00           475 E   1.00           476 N   1.00           477 D   1.00           478 A   1.00           479 A   1.00           480 K   1.00           481 D   1.00           482 E   1.00           483 V   1.00           484 K   1.00           485 E   1.00           486 V   1.00           487 L   1.00           488 Q   1.00           489 A   1.00           490 L   1.00           491 E   1.00           492 E   1.00           493 L   1.00           494 A   1.00           495 V   1.00           496 N   1.00           497 Y   1.00           498 D   1.00           499 Q   1.00           500 K   1.00           501 S   1.00           502 Q   1.00           503 E   1.00           504 V   1.00           505 E   1.00           506 E   1.00           507 K   1.00           508 S   0.99           509 Q   0.99           510 Q   0.97           511 N   0.65           512 Q   0.65           513 L   0.59           514 L   0.59           515 V   0.59           516 D   0.59           517 E   0.59           518 L   0.59           519 S   0.59           520 Q   0.59           521 K   0.59           522 V   0.59           523 A   0.59           524 T   0.61           525 M   0.61           526 L   0.61           527 S   0.61           528 L   0.61           529 E   0.61           530 S   0.61           531 E   0.61           532 L   0.61           533 Q   0.61           534 R   0.61           535 L   0.61           536 Q   0.61           537 E   0.61           538 V   0.61           539 S   0.61           540 G   0.61           541 H   0.61           542 Q   0.61           543 R   0.61           544 K   0.61           545 R   0.61           546 I   0.61           547 A   0.61           548 E   0.61           549 V   0.61           550 L   0.61           551 N   0.61           552 G   0.53           553 L   0.53           554 M   0.53           555 K   0.53           629 Q   0.62           630 L   0.78           631 L   0.95           632 I   0.96           633 S   0.96           634 Q   0.98           635 H   0.98           636 E   1.00           637 A   1.00           638 K   1.00           639 I   1.00           640 R   1.00           641 S   1.00           642 L   1.00           643 T   1.00           644 E   1.00           645 Y   1.00           646 M   1.00           647 Q   1.00           648 S   1.00           649 V   1.00           650 E   1.00           651 L   1.00           652 K   1.00           653 K   1.00           654 R   1.00           655 H   1.00           656 L   1.00           657 E   1.00           658 E   1.00           659 S   1.00           660 Y   1.00           661 D   1.00           662 S   1.00           663 L   1.00           664 S   1.00           665 D   1.00           666 E   1.00           667 L   1.00           668 A   1.00           669 K   1.00           670 L   1.00           671 Q   1.00           672 A   1.00           673 Q   1.00           674 E   1.00           675 T   0.99           676 V   0.99           677 H   0.99           678 E   0.99           679 V   0.99           680 A   0.99           681 L   0.99           682 K   0.99           683 D   0.99           684 K   0.75           685 E   0.75           701 Q   0.85           702 M   0.91           703 E   0.97           704 S   0.97           705 H   0.97           706 R   0.98           707 E   0.98           708 A   0.98           709 H   0.98           710 H   1.00           711 R   1.00           712 Q   1.00           713 L   1.00           714 A   1.00           715 R   1.00           716 L   1.00           717 R   1.00           718 D   1.00           719 E   1.00           720 I   1.00           721 N   1.00           722 E   1.00           723 K   1.00           724 Q   1.00           725 K   1.00           726 T   1.00           727 I   1.00           728 D   1.00           729 E   1.00           730 L   1.00           731 K   1.00           732 D   1.00           733 L   1.00           734 N   1.00           735 Q   1.00           736 K   1.00           737 L   1.00           738 Q   1.00           739 L   1.00           740 E   1.00           741 L   1.00           742 E   1.00           743 K   1.00           744 L   1.00           745 Q   1.00           746 A   1.00           747 D   1.00           748 Y   1.00           749 E   1.00           750 K   1.00           751 L   1.00           752 K   1.00           753 S   1.00           754 E   1.00           755 E   1.00           756 H   1.00           757 E   1.00           758 K   1.00           759 S   1.00           760 T   1.00           761 K   1.00           762 L   1.00           763 Q   1.00           764 E   1.00           765 L   1.00           766 T   0.99           767 F   0.93           768 L   0.77           769 Y   0.77           770 E   0.89           771 R   0.89           772 H   0.89           773 E   0.89           774 Q   0.89           775 S   0.89           776 K   0.89           777 Q   0.89           778 D   0.89           779 L   0.89           780 K   0.89           781 G   0.89           782 L   0.89           783 E   0.89           784 E   0.89           785 T   0.89           786 V   0.89           787 A   0.89           788 R   0.89           789 E   0.89           790 L   0.89           791 Q   0.89           792 T   0.89           793 L   0.89           794 H   0.89           795 N   0.89           796 L   0.89           797 R   0.89           798 K   0.86           799 L   0.72           800 F   0.72           821 G   0.51           822 I   0.91           823 H   0.91           824 S   0.95           825 Q   0.98           826 K   1.00           827 Q   1.00           828 K   1.00           829 I   1.00           830 S   1.00           831 F   1.00           832 L   1.00           833 E   1.00           834 N   1.00           835 N   1.00           836 L   1.00           837 E   1.00           838 Q   1.00           839 L   1.00           840 T   1.00           841 K   1.00           842 V   1.00           843 H   1.00           844 K   1.00           845 Q   1.00           846 L   1.00           847 V   1.00           848 R   1.00           849 D   1.00           850 N   1.00           851 A   1.00           852 D   1.00           853 L   1.00           854 R   1.00           855 C   0.96           856 E   0.96           857 L   0.96           858 P   0.92           859 K   0.95           860 L   0.95           861 E   0.95           862 K   0.95           863 R   0.95           864 L   0.95           865 R   0.95           866 A   0.95           867 T   0.95           868 A   0.95           869 E   0.95           870 R   0.95           871 V   0.95           872 K   0.95           873 A   0.95           874 L   0.95           875 E   0.95           876 G   0.95           877 A   0.95           878 L   0.95           879 K   0.95           880 E   0.95           881 A   0.95           882 V   0.95           883 R   0.95           884 Y   0.95           885 K   0.95           886 S   0.95           887 S   0.91                         total: 413 residues           Final Results (k = 9/23):           60.9%: nuclear           26.1%: cytoplasmic            8.7%: peroxisomal            4.3%: cytoskeletal           &gt;&gt; prediction for CG122634-01 is nuc (k = 23)                  
 
     [0383] 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                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV5a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value                                         AAM78880   Human protein SEQ ID NO 1542 -   7 . . . 918   661/939 (70%)   0.0             Homo sapiens , 963 aa.   6 . . . 941   787/939 (83%)           [WO200157190-A2, 9 AUG. 2001]       AAM79864   Human protein SEQ ID NO 3510 -   7 . . . 918   654/940 (69%)   0.0             Homo sapiens , 979 aa.   21 . . . 957    780/940 (82%)           [WO200157190-A2, 9 AUG. 2001]       ABB63485     Drosophila melanogaster  polypeptide   7 . . . 904   551/946 (58%)   0.0           SEQ ID NO 17247 -  Drosophila     10 . . . 949    699/946 (73%)             melanogaster , 975 aa.           [WO200171042-A2, 27 SEP. 2001]       AAW72746   Drosophila kinesin - Drosophila sp,   7 . . . 904   550/946 (58%)   0.0           975 aa. [US5830659-A,   10 . . . 949    698/946 (73%)           3 NOV. 1998]       AAW72745   Drosophila kinesin N-terminal 411   7 . . . 386   273/383 (71%)   e−159           amino acid residues - Drosophila sp,   10 . . . 392    322/383 (83%)           411 aa. [US5830659-A,           3 NOV. 1998]                  
 
     [0384] In a BLAST search of public sequence databases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5D.  
               TABLE 5D                          Public BLASTP Results for NOV5a                                             Identities/           Protein           Similarities for       Accession       NOV5a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value                                         Q12840   Neuronal kinesin heavy chain   1 . . . 1011   1010/1032 (97%)    0.0           (NKHC) (Kinesin heavy chain   1 . . . 1032   1010/1032 (97%)            isoform 5A) (Kinesin heavy chain           neuron-specific 1) -  Homo sapiens             (Human), 1032 aa.       P33175   Neuronal kinesin heavy chain   1 . . . 1011   983/1032 (95%)   0.0           (NKHC) (Kinesin heavy chain   1 . . . 1027   999/1032 (96%)           isoform 5A) (Kinesin heavy chain           neuron-specific 1) -  Mus musculus             (Mouse), 1027 aa.       S37711   kinesin heavy chain - mouse, 1027   7 . . . 1011   956/1027 (93%)   0.0           aa.   6 . . . 1027   987/1027 (96%)       O60282   Kinesin heavy chain isoform 5C   7 . . . 918     699/939 (74%)   0.0           (Kinesin heavy chain neuron-specific   6 . . . 943     806/939 (85%)           2) -  Homo sapiens  (Human), 957 aa.       BAC41428   MKIAA0531 protein -  Mus     7 . . . 918     696/938 (74%)   0.0             musculus  (Mouse), 987 aa   37 . . . 973     804/938 (85%)           (fragment).                  
 
     [0385] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5E.  
               TABLE 5E                          Domain Analysis of NOV5a                                     Identities/                   Similarities for       Pfam   NOV5a   the Matched   Expect       Domain   Match Region   Region   Value               kinesin   15 . . . 357   178/417 (43%)   8.4e−174               299/417 (72%)       Phosphoprotein   482 . . . 507      7/26 (27%)   0.77                20/26 (77%)                  
 
     Example 6.  
     [0386] 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:25   3515 bp                     NOV6a,     AAAGGGGAGTCCGGTGAACGGGCAGAAGCACGGCCATGCCCAAGCCACCCCCAAGATCCCCCTGAA         CG125312-01       DNA Sequence     CCTGCACCTCCATCACGACCCATTCAGGAGCCTCCAGGAGCCCAGACACCAGCCCCCCACC   ATG GG                   CAGCAACGAGCGCTTCCACTGGCAGAGCCACAACGTGAAGCAGAGCGGCGTCGATGACATGGTGCT                   TCTTCCCCAGATCACCGAAGACGCCATTGCCGCCAACCTCCGGAACCGCTTCATGGACGACTACAT                   CTTCACCTACATCGGCTCTGTGCTCATCTCTGTAAACCCCTTCAAGCAGATGCCCTACTTCACCGA                   CCGTGAGATCCACCTCTATCAGGGCGCGGTGCAGTATGAGAATCCCCCGCACATCTACCCCCTCAC                   GGACAACATGTACCGGAACATGCTTATCGACTGTGAGAACCAGTGTGTCATCATTAGTGGAGAGAG                   TGGAGCTGGAGAGACAGTGGCACCCAAATATATCATGGGCTACATCTCCAACGTGTCTGGCAAAGG                   CGAGAAGGTCCAGCACGTCAAAGATATCATCCTGCAGTCCAACCCGCTGCTCGAGGCCTTCGCCAA                   CGCCAAGACTGTGCGCAACAACAATTCCAGCCGCTTTGGCAAGTACTTTGAGATCCAGTTCAGCCG                   AGGTGGGGAGCCAGATGGGGGCAAGATCTCCAACTTCTTGCTGGAGAAGTCCCGCGTGGTCATGAA                   AAATGAAAATGAGAGGAACTTCCACATCTACTACCAGCTGCTGGAAGGGGCCTCCCAGGAGCAAAG                   GCAGAACCTGGGCCTCATGACACCGGACTACTATTACTACCTCAACCAATCGGACACCTACCAAAT                   GGACGGCACGGACGACAGAAGCGACTTTGGTGAGACTCTGAGTGCTATGCAGGTTATTAAGATCCC                   GCCCAGCATCCAGCAGCTGGTCCTGCAGCTCGTGGCGGGGATCTTGCACCTGGGGAACATCAGTTT                   CTGTGAAGACGGGAATTACGCCCGAGTGGAGAGTGTGGACCTGGCCTTTCCCGCCTACCTGCTCAA                   CATTGACAGCGGGCGACTGCAGGAGAAGCTGACCAGCCGCAAGATGGACAGCCGCTAAAACAAGCC                   CAGCGAGTCCATCAATGTGACCCTCAACGTGGAGCAGGCAGCCTACACCCGTGATGCCCTAACCAA                   GGGGCTCTATGCCCGCCTCTTCGACTTCCTCGTGGAGGCGATCAACCGTGCTATGCAGAAACCCCA                   GGAAGAGTACAGCATCGGTGTGCTGGACATTTACCGCTTCGAGATCTTCCAGAAAAATAACTTCGA                   GCAGTTTTGCATCAACTTCGTCAATGAGAAGCTGCAGCAAATCTTTATCGAACTTACCCTGAAAAC                   CGAGCAGGAGGAGTATGTGCAGGAAGGCATCCGCTGGACTCCAATCCAGTACTTCAACAACAAAGT                   CGTCTGTGACCTCATCGAAAACAAGCTGAGCCCCCCAGGCATCATGAGCGTCTTAAACGACGTGTG                   CGCCACCATCCACGCCACGGGCGGGGGAGCAGACCAGACACTGCTGCAGAAGCTGCAGGCAACTGT                   GGGGACCCACGAGCATTTCAACACCTGGAGCGCCGGCTTCGTCATCCACCACTACGCTGGCAAAAT                   GTCCTACGACGTCAGCGGCTTCTGCGAGAGGATCCGAGACGTTCTCTTCTCCGACCTCATAGAGCT                   GATGCAGACCAGTGAGCAGTTCCTCCGGATGCTCTTCCCCGAGAAGCTGGATGGAGACAACAAGGG                   GCGCCCCAGCACCGCCGGCTCCAAGATCAAGAAACAACCCAACGACCTGGTGGCCACACTGATGAG                   GTGCACACCCCACTACATCCGCTGCATCAAACCCAACGAGACCAAGAAACCCCGAGACTGGGAGGA                   GAACAGGGTCAAGCACCAGGTGGAATACCTGGGCCTGAAGGAGAACATCAGGGTGCGCAGAGCCGG                   CTTCGCCTACCGCCGCCAGTTCGCCAAATTCCTGCAGAGGTATGCCATTCTGACCCCCGAGACGTG                   GCCGCGGTGGCGTGGGGACGAACGCCAGGGCGTCCAGCACCTGCTTCGAACGGTCAACATAAAGCC                   CGACCAGTACCAGATGGGGAGCACCAAGGTCTTTGTCAAGAACCCAGAGTCGCTTTTCCTCCTAAA                   GGAGGTGCGAGAGCGAAAGTTCGATGGCTTTGCCCGAACCATCCAGAAGGCCTGGCGGCGCCACGT                   GGCTGTCCGGAAGTACGAGGAGATGCGGGAGGAAGCTTCCAACATCCTGCTGAACAAGAAGGAGCG                   GAGGCGCAACAGCATCAATCGGAACTTCGTCGGGGACTACCTGGGGCTGGAGGAGCGGCCCGAGCT                   GCGTCAGTTCCTGGGCAAGACGGAGCGGGTGGACTTCGCCGATTCGGTCACCAAGTACGACCGCCG                   CTTCAAGCCCATCAAGCGGGACTTGATCCTGACGCCCAACTGTGTGTATGTGATTGGGCGAGAGAA                   AGTGAAGAAGGAGACCTGAGAGGGCCAGGTGTGTGAAGTCTTGAAGAAGAAAGTAAACATCCAGGC                   TCTGCGGGGAGTCTCCCTCAGCACGCGACACGACGACTTCTTCATCCTCCAAGAGGATGCCGCCGA                   CAGCTTCCTGGAGAGCGTCTTCAAGACCGAGTTTGTCAGCCTTCTGTGCAAGCGCTTCGAGGAAAC                   GACGCGGAGGCCCCTGCCCCTCACCTTCAGCGACAGACTACAGTTTCGGGTGAAGAAGGAGGGCTG                   CGGCGGTGGCGGCACCCGCAGCGTCACCTTCTCCCGCGGCTTCGGCGACTTGGCAGTGCTCAAAAT                   TGGCGGTCGGACCCTCACGGTCAGCGTCGGCGATGGGCTGCCCAAGAGCTCAGAGCCTACGCCGAA                   GGGAATGGCCAAGGGAAAACCTCGGAGGTCCTCCCAAGCCCCTACCCGGGCGGCCCCTGCGCCCCC                   CAGAGGTATCGATCGCAATGGGGTGCCCCCCTCTGCCAGAGGGGGCCCCCTGCCCCTGGAGATCAT                   GTCTGGAGGGGGCACCCACAGGCCTCCCCGGGGCCCTCCGTCCACATCCCTGGGAGCCAGCAGACG                   ACCCCGGGCACGTCCGCCCTCAGAGCACAACACAGAATTCCTCAACGTGCCTGACCAGGGCATAAC                   GGGAATGCAGACGAAGCGCAGCGTGGGGCAACGGCCAGTGCCTGGTGTCGGCCGACCCAAGCCCCA                   GCCTCGGACACATGGTCCCAGGTGCCGGGCCCTATACCAGTACGTAAGCCAAGATGTGGACGAGCT                   GAGCTTCAACGTGAACGAGGTCATTGAGATCCTCATGGAAGATCCCTCGGGCTGGTGGAAGGGCCG                   GCTTCACGGCCAGCAGGGCCTTTTCCCAGGAAACTACGTGGAGAAGATC TGA   GCTGGGCCCTGGGA                       TACTGCCTTCTCTTTCGCCCGCCTATCTGCCTGCCGGCCTGGTGGGGAGCCAGGCCCTGCCAATGA                       GAGCCTCGTTTACCTGG                                           ORF Start: ATG at 128       ORF Stop: TGA at 3416           SEQ ID NO:26   1096 aa   MW at 124743.0 kD                     NOV6a,   MGSKERFHWQSHNVKQSGVDDMVLLPGITEDAIAANLRKRPMDDYIFTYIGSVLISLIPFKQMPYF       CG125312-01       Protein Sequence   TDREIDLYQGAVQYENPPHIYALTDNMYRNNLIDCENQCVIISGESGAGKTVAAKYIMGYISKVSG                   GGEKVQHVKDIILQSNPLLEAFGNAKTVANNNSSRFGKYFEIQFSRGGEPDGGKISNFLLEKSRVV                   MQMENERNFHIYYQLLEGASQEQRQNLGLMTPDYYYYLNQSDTYQVDGTDDRSDFGETLSAMQVIG                   IPPSIQQLVLQLVAGTLMLGNISFCEDGNYARVESVDLAFPAYLLGIDSGRLQEKLTSRKMDSRWG                   GRSESINVTLNVEQAAYTRDALAKGLYARLFDFLVEAIWRAMQKPQEEYSIGVLDIYGFEIFQKNG                   FEQFCINEVNEKLQQIFIELTLKAEQEEYVQEGIRWTPIQYFNNKVVCDLIENKLSPPGIMSVLDD                   VCATMMATGGGADQTLLQKLQAAVGTHEHFNSWSAGFVIHHYAGKVSYDVSGFCERNRDVLFSDLI                   ELMQTSEQFLRNLFPEKLDGDKKGRPSTAGSKIKKQANDLVATLMRCTPHYIRCIKPNETKRPRDW                   EENRVKHQVEYLGLKENIRVRRAGFAYRRQFAKFLQRYAILTPETWPRWRGDERQGVQHLLRAVNN                   EPDQYQMGSTKVFVKNPESLFLLEEVRERKFDGFARTIQKAWRRHVAVRKYEEMREEASNILLMKK                   ERRRNSINRNFVGDYLGLEERPELRQFLGKRERVDFADSVTKYDRRFKPIKRALILTPKCVYVIGR                   EKVKKGPEKGQVCEVLKKKVDIQALRGVSLSTRQDDFFILQEDAADSFLESVFKTEFVSLLCKRFE                   EATRRPLPLTFSDRLQFRVKKEGWGGGGTRSVTFSRGFGDLAVLKVGGRTLTVSVGDGLPKSSEPT                   RKGMAKGKPRRSSQAPTRAAPAPPRGMDRNGVPPSARGGPLPLEIMSGGGTHRPPRGPPSTSLGAS                   RRPRARPPSEHNTEFLNVPDQGMAGMQRKRSVGQRPVPGVGRPKPQPRTHGPRCRALYQYVGQDVD                   ELSFNVNEVIEILMEDPSGWWKGRLHGQEGLFPGNYVEKI                  
 
     [0387] Further analysis of the NOV6a protein yielded the following properties shown in Table 6B.  
               TABLE 6B                       Protein Sequence Properties NOV6a                                        SignalP analysis:   No Known Signal Sequence Predicted       PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 6; pos. chg 2; neg. chg 1           H-region: length 8; peak value −3.21           PSG score: −7.61           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −6.60           possible cleavage site: between 34 and 35           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 1           Number of TMS(s) for threshold 0.5: 0           PERIPHERAL Likelihood = 3.18 (at 41)           ALOM score: −1.22 (number of TMSs: 0)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   1   Hyd Moment(75):   7.74           Hyd Moment(95):   4.20   G content:   2           D/E content:   2   S/T content:   3                             Score: −6.18                             Gavel: prediction of cleavage sites for mitochondrial preseq           R-2 motif at 16 ERF|HW           NUCDISC: discrimination of nuclear localization signals           pat4: KRPR (4) at 589           pat4: KPRR (4) at 932           pat4: RRPR (4) at 991           pat7: none           bipartite: KRERVDFADSVTKYDRR at 756           bipartite: KKGPEKGQVCEVLKKKV at 796           content of basic residues: 14.3%           NLS Score: 1.27           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           KKXX-like motif in the C-terminus: YVEK           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 76.7           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           60.9%: cytoplasmic           34.8%: nuclear           4.3%: peroxisomal           &gt;&gt; prediction for CG125312-01 is cyt (k = 23)                  
 
     [0388] 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                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV6a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value                                         AAU97544   Human Myosin-1F protein    1 . . . 1096   1089/1098 (99%)    0.0           MYO1F -  Homo sapiens , 1098 aa.    1 . . . 1098   1092/1098 (99%)            [WO200218946-A2, 7 MAR. 2002]       ABB97258   Novel human protein SEQ ID NO:    63 . . . 1096   994/1097 (90%)    0.0           526 -  Homo sapiens , 1089 aa.    1 . . . 1089   1006/1097 (91%)            [WO200222660-A2, 21 MAR. 2002]       AAM39991   Human polypeptide SEQ ID NO   18 . . . 718   327/724 (45%)   e−173           3136 -  Homo sapiens , 1063 aa.   47 . . . 761   453/724 (62%)           [WO200153312-A1, 26 JUL. 2001]       ABG10171   Novel human diagnostic protein   18 . . . 718   327/724 (45%)   e−173           #10162 -  Homo sapiens , 1050 aa.   33 . . . 747   453/724 (62%)           [WO200175067-A2, 11 OCT. 2001]       AAB64616   Human secreted protein BLAST   18 . . . 686   319/701 (45%)   e−169           search protein SEQ ID NO: 126 -   16 . . . 697   438/701 (61%)             Homo sapiens , 697 aa.           [WO200077197-A1, 21 DEC. 2000]                  
 
     [0389] In a BLAST search of public sequence databases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6D.  
               TABLE 6D                          Public BLASTP Results for NOV6a                                             Identities/           Protein           Similarities for       Accession       NOV6a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value                                         O00160   Myosin If (Myosin-IE) -  Homo     1 . . . 1096   1089/1098 (99%)    0.0             sapiens  (Human), 1098 aa.   1 . . . 1098   1092/1098 (99%)        P70248   Myosin If -  Mus musculus     1 . . . 1096   993/1107 (89%)   0.0           (Mouse), 1099 aa.   1 . . . 1099   1042/1107 (93%)        CAD34774   Sequence 82 from Patent   63 . . . 1096    994/1097 (90%)   0.0           WO0222660 -  Homo sapiens     1 . . . 1089   1006/1097 (91%)            (Human), 1089 aa.       Q90748   Brush border myosin IB -  Gallus     1 . . . 1096   917/1102 (83%)   0.0             gallus  (Chicken), 1099 aa.   1 . . . 1099   996/1102 (90%)       Q63356   Myosin Ie (Myosin heavy chain   1 . . . 1096   793/1115 (71%)   0.0           myr 3) -  Rattus norvegicus  (Rat),   1 . . . 1107   929/1115 (83%)           1107 aa.                  
 
     [0390] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6E.  
               TABLE 6E                          Domain Analysis of NOV6a                                             Identities/                   NOV6a   Similarities for           Pfam   Match   the Matched   Expect           Domain   Region   Region   Value                                                 myosin   19 . . . 675   336/736 (46%)    0           _head       549/736 (75%)            IQ   692 . . . 712     8/21 (38%)   0.96                   16/21 (76%)           SH3   1042 . . . 1096    28/58 (48%)   2.2e−20                   49/58 (84%)                      
 
     Example 7.  
     [0391] 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:27   1520 bp                     NOV7a,     TCACCGGCGCCGAGATGCGGTTCCGGCGCTTAGGGCGCCGCTAAACTCAGAGCCCGGGAGTCATGG         CG134632-01       DNA Sequence     CTGCGGGCGGTGCCGCCCCAGGTAAATCAGTCCAGGAGCAGGGCCCGGGCCTGGCGTACACTCTGC                       GAAAAATGGGGGCCAGAGCAAACAAGAAGAGCGAAAGCAAGAGGGCTAGGCAGCCAGAGGCGGCAG                       CAAGACTCAAGACGCCAACGGCGCCGTCTTCCTGGGGCCCCAGGGCCTGCGCCATCCCTGGGCTGC                       CGGGGCACCGCCTCTCCACGCCCCTCGTCCGGCGGCGGCTGCGACTGCTTCCGAGGTCATGTTCCC                       AGGACAGGGCGCGTCTTCAGGGTGGAAGCCTGGCGCACGTCCGAGGTGCCGAGGACCCAACCAGCC                       CAAACTCTGGGGGAAA   TGA CTCCCCTCTGCCCTCGCCCCGCGCTCTGCTACCATTTCCTTACGTCT                   CTGCTTCGCTCAGCGATGCAAAACGCGCGAGGCGCACGGCAGAGGGCCAAAGCCGCGGTACTCTCC                   GGGCCAGGCCCGCCCCTCGGCCGCGCCGCGCAGCACGGGATTCCCCGGCCGCTGTCCAGCGCTGGC                   CGCCTGAGCCAAGGCTGCCGCGGAGCCAGTACAGTCGGGGCCGCTGGCTGGAAGAACGAGCTTCCT                   AAGGCGGGGGGGAGCCCGGCGCCGGGGCCGGAGACACCCGCCATTTCACCCAGTAAGCGAACCCGG                   CCTGCGGAGGTGGGCGGCATGCAGCTCCGCTTTGCCCGGCTCTCCGAGCACGCCACGGCCCCCACC                   CGGGGCTCCGCGCGCGCCGCGGGCTACGACCTGTACAGTGCCTATGATTACACAATACAACCTATG                   GAGAAACCTGTTGTGAAAACGGACATTCAGATAGCGCTCCCTTCTCAATGTTATGGAAGAGTAACT                   CCACCGTCAGGCTTGGCTGCAAAACACTTTATTGATGTAGCAGCTGGTGTCATAGATGAAGATTAT                   AGAGGAAATGTTGGTGTTGTACTGTTTAATTTTGGCAAAGAAAAGTTTGAAGTCAAAAAAGGTGAT                   CGAATTGCACAGCTCATTTGCGAACGGATTTTTTATCCAGAAATAGAAGAAGTTCAAGCCTTGGAT                   GACACCGAAAGGGGTTCAGGAGGTTTTGGTTCCACTGGAAAGAA TAA   AATTTTATGCCAAGAACAG                       AAAACAAGAAGTCATACCTTTTTCTTAAAAAAAAAAAAAAAGTTTTTGCTTCAAGTGTTTTGGTGT                       TTTGCACTTCTGTAAACTTACTAGCTTTACCTTCTAAAAGTACTGCATTTTTTACTTTTTTTTATG                       ATCAAGGAAAAGATCATTAAAAAAAAACACAAAGAAGTTTTTCTTTGTGTTTGGATCAAAAAGAAA                       CTTTGTTTTTCCGCAATTGAAGGTTGTATGTAAATCTGCTTTGTGGTGACCTCATGTAAACAGTGT                       TTCTTAAAATCAAATGTAAATCAATTCCCGATTAAAAAAAAAAGCCTGTATTTAACTCAAAAAAAA                                           ORF Start: ATG at 412       ORF Stop: TAA at 1168           SEQ ID NO:28   252 aa   MW at 26562.9 kD                     NOV7a,   MTPLCPRPALCYHFLTSLLRSANQNARGARQRAEAAVLSGPGPPLGRAAQHGIPRPLSSAGRLSQG       CG134632-01       Protein Sequence   CRGASTVGAAGWKGELPKAGGSPAPGPETPAISPSKRARPAEVGGMQLRFARLSEHATAPTRGSAP                   AAGYDLYSAYDYTIPPMEKAVVKTDIQIALPSGCYGRVAPRSGLAAKHFIDVGAGVIDEDYRGNVG                   AAVLFNFGKEKFEVKKGDRIAQLICERIFYPEIEEVQALDDTERGSGGFGSTGKN                                     SEQ ID NO:29   916 bp                     NOV7b,     GTTCCCAGGACGGGCGCGTCTTCAGGGTGGAACCTGGCGCACGTCCGGAGGTGCCGAAAACCCAA         CG134632-02       DNA Sequence     CAGCCCAAACTCTGGGAGAA   ATG ACTCCCCTCTGCCCTCGCCCCGCCCTCTGCTACCATTTCCTT                   ACGTCTCTGCTTCGCTCAGCGATGCAAAACGCGCCAGGCGCACGGCAGAAAGCCGAAAGCCGCGGTA                   CTCTCCGGGCCAGGCCCGCCCCTCGGCCGCGCCGCGCAGCACGGGATTCCCCGGCCGCTGTCCAGC                   GCTGGCCGCCTGAGCCAAGGCTGCCGCGGAGCCPAGACACCCGCCATTTCACCCAGTAAGCCAACC                   CGGCCTGCGGAGGTGGGCGGCATGCAGCTCCGCTTTGCCCGGCTCTCCGAGCACGCCACAACCCCC                   ACCCGGGGCTCCGCCCGCGCCGCGGGCTACGACCTGTACAGTGCCTATGATTACACAATACCACCT                   ATGGAGAAAGCTGTTGTCAAAACGGACATTCAGATAGCGCTCCCTTCTGCGTGTTATGGAAGAGTG                   GCTCCACGGTCAGGCTTGGCTGCAAAACACTTTATTGATGTAGGAGCTGGTGTCATAGATGAAGAT                   TATAGAGGAAATGTTGGTGTTGTACTGTTTAATTTTGGCAAAGAAAAGTTTGAAGTCAAAAAAGGT                   GATCCAATTGCACAGCTCATTTGCGAACGGATTTTTTATCCAGAAATAGAAGAAGTTCAAGCCTTG                   GATGACACCGAAAGGGGTTCAGGAGGTTTTGGTTCCACTGGAAAGAAT TAA   AATTTATGCCAAGAA                       CAGAAAACAAGAAGTCATACCTTTTTCTTAAAAAAAAAAAAAGTTTTTGCTTCPAGTGTTTTGGTG                       TTTTGCACTTCTGTAAACTTACTAGCTTTACCTTCTAAAAGTACTGCATTTTTTACTT                                           ORF Start: ATG at 88       ORF Stop: TAA at 775           SEQ ID NO:30   229 aa   MW at 24487.7 kD                     NOV7b,   MTPLCPRPALCYHFLTSLLRSAMQNARGARQRAEAAVLSGPGPPLGAAQHGIPRPLSSAGRLSQG       CG134632-02       Protein Sequence   CRGAKTPAISPSKRARPAEVGGMGLFARLSEHATAPTRGSARAAGYDLYSAYDYTIPPMEKAVVK                   TDIQIALPSGCYGRVAPRSGLAAKHFIDVGAGVIDEDYRGNGVTLFNFGAAKFEVKKGDRIAQLI                   ERIFYPEIEEVQALDDTERGSGCFGSTGKN                                     SEQ ID NO:31   1816 bp                     NOV7c,     CTCGCCTTCTGGCTCTGCC   ATG CCCTGCTCTGAAGAGACACCCGCCATTTCACCCAGTAAGCGGGC       CG134632-03       DNA Sequence   CCGGCCTGCGGAGGTGCGCGCCATGCAGCTCCGCTTTGCCCGGCTCTCCGAGCACGCCACGGCCCC                   CACCCGGCGCTCCGCGCGCGCCGCGGGCTACGACCTGTACAGTGCCTATGATTACACAATACCACC                   TATGGAGAAAGCTGTTGTGAAAACGGACATTCAGATAGCGCTCCCTTCTGGGTGTTATGGAAGAGT                   GGCTCCACGGTCAGGCTTGGCTGCAAAACACTTTATTGATGTAGGAGCTGGTGTCATAGATGAAGA                   TTATAGAGGAAATGTTGGTGTTGTACTGTTTAATTTTGGCAAAGAAAAGTTTGAAGTCAAAAAAGG                   TGATCGAATTGCACAGCTCATTTGCGAACGGATTTTTTATCCAGAAATAGAAGAAGTTCAAGCCTT                   GGATGACACCGAAAGGGGTTCAGGAGGTTTTGGTTCCACTGGAAAGAAT TAA   AATTTATGCCAAGA                       ACAGAAAACAAGAAGTCATACCTTTTTCTTAAAAAAAAAAAAAAAGTTTTTGCTTCAAGTGTTTTG                       GTGTTTTGCACTTCTGTAAACTTACTAGCTTTACCTTCTAAAAGTACTGCATTTTTTACTTTTTTT                       TATGATCAAGGAAAAGATCGTTAAAAAAAAACACAAAGAAGTTTTTCTTTGTGTTTGGATCAAAAA                       GAAACTTTGTTTTTCCGCAATTGAAGGTTGTATGTAAATCTGCTTTGTGGTGACCTGATGTAAACA                       GTGTCTTCTTAAAATCAAATGTAAATCAATTACAGATTAAAAAAAAAAGCCTGTATTTAACTCATA                       TGATCTCCCTTCAGCAACTTATTTTGCTTTAATTGCTTTAAATCTTAAGCAATATTTTTTATTCAG                       TAAACAAATTCTTTCACAAGGTACAAAATCTTGCATAAGCTGAACTAAAATAAAAATGAAAAGGAG                       AGATTAAAGGTATTCCTTGTTCTTCCCTTCTCTTCACTAGTCTAAAAACTTCTTTTTAATCTTAAG                       ATTCTTTGTGATGAGGGTGAGAAAAAGAATCCTCAGTTTATTTTTCCACTATTAATCTTTCTTTTG                       ATAAATCCTCTATTGACTGGGTAGAGGTATGTTTGTGAAAGACATGTAACTTGGGGATTTGTTACT                       TTAGGTTTGTTCCCTTGAATTTCATCTCATCAGGCAAATTGTACTAGTTGTAGTTACGAGTTTTCC                       CTCAGTGAAGTAGCAATAGGCTGTAATCAAGAAAATATCCCATTTATAGAGATAAGATAAATGAAA                       TAATACTTCAGCCACCAGGTTTTTCTGTCTCACATACATAAGCAGCATTTCATTGCAGATATAAGA                       CTGATTCTGTGGCTTACCTTGATTAACATCTTTTGGAAGTTTTGCTAGTGTGCTTTCCTTTCTTTA                       CTATGTTTCTCAGATTCCTTTGTATCAGGGTTTTGGGTGTCACTTAGGTTTTGTCCATCAGATTCT                       GTGAGACACCAGGCATCGTTTTGAGGATGTGCGTTATACACATGGAGTGCTTCTGGAACTATCAGC                       CCACTTGACCACCCAGTTTGTGGAAGCACAGGCAAGAGTGTTCTTTTCTGGTCATTCTCCAGGCCA                       TTTAATACCCTGCAATGTAATTGTCCCTCTGTGGCTCACATTTCATTAGTGAGCCATGAAATCAAC                       TCAGTGGGACATAGCCAGCATTTTTGCATACCAGGTTGCGCTATAAAATATTTCTGTTGTCAATAA                       ATTTTAATGTTTTCCTGCTAAAAAAAAAAAAAAA                                           ORF Start: ATG at 20       ORF Stop: TAA at 512           SEQ ID NO:32   164 aa   MW at 17747.9 kD                     NOV7c,   MPCSEETPAISPSKRARPAEVGGMQLRFARLSEHATAPTRGSARAAGYDLYSAYDYTIPPMEKAVV       CG134632-03       Protein Sequence   KTDIQIALPSGCYGRVAPRSGLAAKHFIDVGAGVIDEDYRGNVGVVLFNFGKEKFEVKKGDRIAQL                   ICERIFYPEIEEVQALDDTERGSGGFGSTGKN                  
 
     [0392] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 7B.  
               TABLE 7B                          Comparison of NOV7a against NOV7b and NOV7c.                                         Identities/                   Similarities for           Protein   NOV7a Residues/   the Matched           Sequence   Match Residues   Region                       NOV7b   1 . . . 252   228/252 (90%)               1 . . . 229   229/252 (90%)           NOV7c   94 . . . 252     159/159 (100%)               6 . . . 164    159/159 (100%)                      
 
     [0393] Further analysis of the NOV7a protein yielded the following properties shown in Table 7C.  
               TABLE 7C                       Protein Sequence Properties NOV7a                                        SignalP analysis:   Cleavage site between residues 29 and 30       PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 7; pos. chg 1; neg. chg 0           H-region: length 12; peak value 5.44           PSG score: 1.04           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −4.15           possible cleavage site: between 21 and 22           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 7.21 (at 174)           ALOM score: 7.21 (number of TMSs: 0)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 6           Charge difference: 0.5 C(2.5)-N(2.0)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt;Caution: Inconsistent mtop result with signal peptide           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   5   Hyd Moment (75):   8.02           Hyd Moment (95):   9.18   G content:   1           D/E content:   1   S/T content:   4                         Score: 0.92           Gavel: prediction of cleavage sites for mitochondrial preseq           R-2 motif at 142 ARA|AG           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: PSKRARP (4) at 100           bipartite: none           content of basic residues: 12.7%           NLS Score: −0.13           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           KKXX-like motif in the C-terminus: STGK           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 55.5           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           78.3%: mitochondrial            4.3%: Golgi            4.3%: cytoplasmic            4.3%: nuclear            4.3%: peroxisomal            4.3%: endoplasmic reticulum           &gt;&gt; prediction for CG134632-01 is mit (k = 23)                  
 
     [0394] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7D.  
               TABLE 7D                          Geneseq Results for NOV7a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV7a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value               AAW30281   Human dUTPase (mitochondrial   1 . . . 252   235/252 (93%)    e−134           form) -  Homo sapiens , 252 aa.   1 . . . 252   236/252 (93%)           [WO9736916-A1, 09 OCT. 1997]       AAW30280   Human dUTPase (nuclear form) -   94 . . . 252     159/159 (100%)   3e−88             Homo sapiens , 164 aa.   6 . . . 164    159/159 (100%)           [WO9736916-A1, 09 OCT. 1997]       AAR70144   Human dUTPase protomer -  Homo     112 . . . 252     141/141 (100%)   2e−77             sapiens , 141 aa. [CA2126001-A,   1 . . . 141    141/141 (100%)           28 JAN. 1995]       ABB60791     Drosophila melanogaster  polypeptide   104 . . . 250     96/147 (65%)   1e−50           SEQ ID NO 9165 -  Drosophila     12 . . . 158    114/147 (77%)             melanogaster , 188 aa.           [WO200171042-A2, 27 SEP. 2001]       AAB44003   Human cancer associated protein   94 . . . 185     91/92 (98%)   2e−46           sequence SEQ ID NO: 1448 -  Homo     12 . . . 103     91/92 (98%)             sapiens , 106 aa. [WO200055350-A1,           21 SEP. 2000]                  
 
     [0395] In a BLAST search of public sequence databases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7E.  
               TABLE 7E                          Public BLASTP Results for NOV7a                                             Identities/           Protein           Similarities for       Accession       NOV7a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value               P33316   Deoxyuridine 5′-triphosphate   1 . . . 252   235/252 (93%)    e−134           nucleotidohydrolase, mitochondrial   1 . . . 252   236/252 (93%)           precursor (EC 3.6.1.23) (dUTPase)           (dUTP pyrophosphatase) -  Homo               sapiens  (Human), 252 aa.       Q96Q81   dUTP pyrophosphatase -  Homo     94 . . . 252     159/159 (100%)   1e−87             sapiens  (Human), 164 aa.   6 . . . 164    159/159 (100%)       A46256   dUTP pyrophosphatase (EC 3.6.1.23) -   112 . . . 252     141/141 (100%)   5e−77           human, 141 aa.   1 . . . 141    141/141 (100%)       Q9CU90   5133400F09Rik protein -  Mus     31 . . . 252    154/222 (69%)   4e−76             musculus  (Mouse), 204 aa (fragment).   3 . . . 204   167/222 (74%)       Q8VCG1   Similar to dUTPase -  Mus musculus     30 . . . 252    154/225 (68%)   1e−74           (Mouse), 200 aa.   9 . . . 200   167/225 (73%)                  
 
     [0396] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7F.  
               TABLE 7F                          Domain Analysis of NOV7a                                             Identities/                   NOV7a   Similarities for           Pfam   Match   the Matched   Expect           Domain   Region   Region   Value                       dUTPase   121 . . . 250   71/138 (51%)   1.1e−64                   123/138 (89%)                       
 
     Example 8.  
     [0397] 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:33   960 bp                     NOV8a,     GTGAGTTGGCTGCCGGTGAGTTGGGTGCCGGTGGAGTCGTGTTGGTCCTCAGAATCCCCGCGTAGCee          CG148411-01       DNA Sequence     CGCTGCCTCCTCCTACCCTCGCCATGTTTCTTACCCGGTCTGAGTACGACAGCTTAATTCTACAGC                       CATTGGGATCCAGACATCAGAGGGTGTGTGCCTAGCTGTGGAGAAGAGAATTACTTCCCCACTG   AT                       G GAGCCCAGCAGCATTGAGAAAATTGTAGAGATTGATGCTCACATAGGTTGTCCAATGAGTGAACT                   AATTGCTGATGCTAAGACTTTAATTGATAAAGCCAGAGTGGAGACACAGAACCACTGGTTCACCTA                   CAATGAGACAATGACAGTGGAGAGTGTGACCCAAGCTGTGTCCAATCTGGCTTTGCAGTTTGGAGA                   AGAAGATGCAGATCCAGGTGCCATGTCTCGTCCCTTTGGAGTAGCATTATTATTTGGAGGAGTTGA                   TGAGAAAGGACCCCAGCTGTTTCATATGGACCCATCTGGGACCTTTGTACAGTGTGATGCTCGAGC                   AATTGGCTCTGCTTCAGAGGGTGCCCAGAGCTCCTTGCAAGAACTTTACCACAAGTCTATGACTTT                   GAAAGAAGCCATCAAGTCTTCACTCATCATCCTCAAACAAGTAATGGAGGAGAAGCTGAATGCAAC                   AAACATTGAGCTAGCCACAGTGCAGCCTGGCCAGAATTTCCACATGTTCACAAAGGAAGAACTTGA                   AGAGGTTATCAAGGACATT TAA   CGAATCCTGATCCTCAGAACTTCTCTGGGACAATTTCAGTTCTA                       ATAATGTCCTTAAATTTTATTTCCAGCTCCTGTTCCTTGGAAAATCTCCATTGTATGTGCATTTTT                       TAAATGATGTCTGTACATAAGGCAGTTCTGAAATAAAGAAATTTTAAAATAAAAAAAAAAAAAAAA                       AAAAAAAAAAAAAAAAAAAAAAA                                           ORF Start: ATG at 197       ORF Stop: TAA at 746           SEQ ID NO:34   183 aa   MW at 20048.5 kD                     NOV8a,   MFPSSIEKIVEIDAHIGCAMSGLIADAKTLIDKARVETQNHWFTYNETMTVESVTQAVSNLALQFG       CG148411-01       Protein Sequence   EEDADPGAMSRPFGVALLFGGVDEKGPQLFHMDPSGTFVQCDARAIGSASEGAQSSLQELYHKSMT                   ILKEAIESSLIILKQVMEEKLNATNIELATVQPCQNFHMFTKEELEEVIKDI                                     SEQ ID NO:35   959 bp                     NOV8b,     CTGCCTCCTCCTACCCTCGCC   ATG TTTCTTACCCGGTCTQAGTACGACAGGGGCGTGAATACTTTT       CG148411-02       DNA Sequence   TCTCCCGAAGGAAGATTATTTCAAGTGGAATATGACATTGAGGCTATCAAGCTTGGTTCTACAGCC                   ATTGGGATCCAGACATCAGAGGGTGTGTCCCTAGCTGTGGAGAAGAGAATTACTTCCCCACTGATG                   GAGCCCAGCAGCATTGAGAAAATTGTAGAGATTGATGCTCACATAGGTTGTGCCATGAGTGGGCTA                   ATTGCTGATGCTAAGACTTTAATTGATAAAGCCAGAGTGGAGACACAGAACCACTGGTTCACCTAC                   AATGAGACAATGACAGTGGAGAGTGTGACCCAAGCTGTGTCCAATCTGGCTTTGCAGTTTGGAGAA                   GAAGATGCAGATCCAGGTGCCATGTCTCGTCCCTTTGGAGTAGCATTATTATTTGGAGGAGTTGAT                   GAGAAACGACCCCAGCTGTTTCATATGGACCCATCTGGGACCTTTGTACAGTGTCATGCTCGAGCA                   ATTGGCTCTGCTTCAGAGGGTGCCCAGAGCTCCTTGCAAGAACTTTACCACAAGTCTATGACTTTG                   AAAGAAGCCATCAAGTCTTCACTCATCATCCTCAAACAAGTAATCGAGGAGAAGCTGAATGCAACA                   AACATTGAGCTAGCCACAGTGCAGCCTGGCCACAATTTCCACATGTTCACAAAGGAAGAACTTGAA                   GAGGTTATCAAGGACATT TAA   GGAATCCTGATCCTCAGAACTTCTCTGGGACAATTTCAGTTCTAA                       TAATGTCCTTAAATTTTATTTCCAGCTCCTGTTCCTTGGAAAATCTCCATTCTATCTGCATTTTTT                       AAATGATGTCTGTACATAAACGCAGTTCTGAAATAAAGAAAATTTTAAAATAAAAAAAAAAAAAAA                       AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA                                           ORF Start: ATG at 22       ORF Stop: TAA at 745           SEQ ID NO:36   241 aa   MW at 26468.8 kD                     NOV8b,   MFLTRSEYDRGVNTFSPEGRLFQVEYDIEAIKLGSTAIGIQTSEGVCLAVEKRITSPLMEPSSIEK       CG148411-02       Protein Sequence   IVEIDAHIGCANSGLTADAKTLIDKARVETQNNWFTYNETMTVESVTQAVSNLALQFGEEDADPGA                   MSRPFGVALLFGGVDEKGPQLFHMDPSGTFVQCDARAIGSASEGAQSSLQELYHKSMTLKEAIKSS                   LIILKQVMEEKLNATNIELATVQPGQNFHMFTKEELEEVIKDI                  
 
     [0398] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 8B.  
               TABLE 8B                          Comparison of NOV8a against NOV8b.                                         Identities/                   Similarities for           Protein   NOV8a Residues/   the Matched           Sequence   Match Residues   Region                       NOV8b   1 . . . 183   183/183 (100%)               59 . . . 241    183/183 (100%)                      
 
     [0399] Further analysis of the NOV8a protein yielded the following properties shown in Table 8C.  
               TABLE 8C                       Protein Sequence Properties NOV8a                                        SignalP analysis:   No Known Signal Sequence Predicted       PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 11; pos. chg 1; neg. chg 3           H-region: length 1; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −8.07           possible cleavage site: between 29 and 30           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 1.54 (at 9)           ALOM score: 1.54 (number of TMSs: 0)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   0   Hyd Moment (75):   8.84           Hyd Moment (95):   5.71   G content:   0           D/E content:   2   S/T content:   2                         Score: −6.11           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 7.7%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           KKXX-like motif in the C-terminus: VIKD           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 89           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           60.9%: cytoplasmic           13.0%: mitochondrial           13.0%: nuclear            8.7%: peroxisomal            4.3%: plasma membrane           &gt;&gt; prediction for CG148411-01 is cyt (k = 23)                  
 
     [0400] A search of the NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8D.  
               TABLE 8D                          Geneseq Results for NOV8a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV8a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value               AAB35091   Proteasome subunit Zeta protein   1 . . . 183    183/183 (100%)   e−100           sequence - Unidentified, 241 aa.   59 . . . 241     183/183 (100%)           [WO200072008-A2, 30 NOV. 2000]       AAY58476   Proteasomal zeta subunit -   1 . . . 183    183/183 (100%)   e−100           Unidentified, 241 aa.   59 . . . 241     183/183 (100%)           [WO9966065-A2, 23 DEC. 1999]       AAM40689   Human polypeptide SEQ ID NO   1 . . . 183   182/183 (99%)   e−100           5620 -  Homo sapiens , 249 aa.   67 . . . 249    183/183 (99%)           [WO200153312-A1, 26 JUL. 2001]       AAM38903   Human polypeptide SEQ ID NO   1 . . . 183   182/183 (99%)   e−100           2048 -  Homo sapiens , 241 aa.   59 . . . 241    183/183 (99%)           [WO200153312-A1, 26 JUL. 2001]       AAM79994   Human protein SEQ ID NO 3640 -   1 . . . 183   182/183 (99%)   e−100             Homo sapiens , 249 aa.   67 . . . 249    183/183 (99%)           [WO200157190-A2, 09 AUG. 2001]                  
 
     [0401] In a BLAST search of public sequence databases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8E.  
               TABLE 8E                          Public BLASTP Results for NOV8a                                             Identities/           Protein           Similarities for       Accession       NOV8a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value               S17521   multicatalytic endopeptidase complex   1 . . . 183    183/183 (100%)    e−100           (EC 3.4.99.46) zeta chain - human, 241   59 . . . 241     183/183 (100%)           aa.       P28066   Proteasome subunit alpha type 5 (EC   1 . . . 183    183/183 (100%)    e−100           3.4.25.1) (Proteasome zeta chain) (EC   59 . . . 241     183/183 (100%)           3.4.25.1) (Macropain zeta chain)           (Multicatalytic endopeptidase complex           zeta chain) -  Homo sapiens  (Human),           241 aa.       Q9Z2U1   Proteasome subunit alpha type 5 (EC   1 . . . 183   182/183 (99%)   1e−99           3.4.25.1) (Proteasome zeta chain) (EC   59 . . . 241    183/183 (99%)           3.4.25.1) (Macropain zeta chain)           (Multicatalytic endopeptidase complex           zeta chain) -  Mus musculus  (Mouse),           241 aa.       P34064   Proteasome subunit alpha type 5 (EC   1 . . . 183   181/183 (98%)   6e−99           3.4.25.1) (Proteasome zeta chain) (EC   59 . . . 241    182/183 (98%)           3.4.25.1) (Macropain zeta chain)           (Multicatalytic endopeptidase complex           zeta chain) -  Rattus norvegicus  (Rat),           241 aa.       Q95083   Proteasome subunit alpha type 5 (EC   1 . . . 183   117/185 (63%)   2e−61           3.4.25.1) -  Drosophila melanogaster     59 . . . 243    147/185 (79%)           (Fruit fly), 244 aa.                  
 
     [0402] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8F.  
               TABLE 8F                          Domain Analysis of NOV8a                                             Identities/                       Similarities for           Pfam   NOV8a   the Matched   Expect           Domain   Match Region   Region   Value                       proteasome   1 . . . 128    56/135 (41%)   5.3e−49                   120/135 (89%)                      
 
     Example 9  
     [0403] 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:37   4650 bp                     NOV9a,     ATG AGCCTTTCATTTTGTGGTAACAACATTTCTTCATATAATATCAACGATGGTGTACTACAAAAT       CG54077-01       DNA Sequence   TCCTGCTTTGTGGATGCCCTCAACCTGGTCCCTCATGTCTTTCTGTTGTTTATCACTTTTCCAATA                   TTGTTTATTGGGTGGGGGAGCCAAAGCTCAAAAGTACAAATTCACAACAACACATGGCTTCATTTT                   CCGGGACATAACCTGAGATGGATTCTTACATTCGCTCTCCTGTTTGTGCATGTCTGTGAAATAGAA                   GAAGGCATTGTTTCAGACTCGCGGCGAAAATCAAGGCACCTCAACCTCTTTATGCCAGCCGTGATG                   GGATTCGTTGCCACTACAACATCGATAGTGTATTATCATAATATCGACATCAAAAATTTTCCTAAA                   TTACTTTTAGCCCTGTTCCTGTATTGGGTAATGGCCTTTATTACAAAAACAATAAAATTGGTTAAG                   TACTGTCAGTCTGGCTTGGACATATCAAACCTGCGTTTCTGCATCACAGGCATGATAATCATCTTG                   AATGGGCTCTTGATGGCTGTGGAGATCAATGTCATTCGAGTCAGGAGATATGTATTTTTCATGAAT                   CTCCACAAAGTAAAGCCTCCTGAAGACCTCCAGGATCTGGGAGTGAGATTTCTTCAACCATTTGTG                   AATTTGCTGTCAAAAGCAACATACTGGTGGATGAACACACTTATTATATCTGCTCACAAAAAGCCT                   ATTGATCTGAAGGCAATTGGAAAATTGCCAATAGCAATGAGAGCAGTAACAAATTATGTTTGCCTG                   AAAGATGCATATGAAGAACAAAAGAAAAAAGTTGCAGATCATCCAAATCGGACTCCATCTATATGG                   CTTGCAATGTACAGAGCTTTTGGGCGACCAATTCTACTTAGTAGCACATTCCGCTATCTAACTGAT                   TTACTGGGTTTTGCTGGACCTCTTTGTATTTCTGGAATAGTTCAGCGTGTGAATGAAACCCAGAAT                   GGGACAAATAACACAACTGGAATTTCAGAAACCCTCTCATCAAAGGAATTTCTTGAAAACGCTTAC                   GTTCTAGCAGTTCTTCTCTTCTTGGCTCTTATTCTGCAAAAGACATTTTTGAAGGCTTCCTACTAT                   GTAACCATAGACACTGGCATTAACCTCCGTGGAGCTCTGCTGGCCATGATTTATAATAAAATCCTT                   AGGCTCTCTACGTCTAACTTATCCATGGGGGAGATGACTCTGGGGCAGATCAACAACTTAGTCGCC                   ATTGAAACTAATCAACTCATGTGGTTTTTGTTCCTGTGTCCCAATCTATGGGCTATGCCTGTTCAG                   ATCATAATGGGCGTGATTCTGCTCTATAATTTACTTGGATCAAGTGCATTGGTCGGTGCAGCTGTC                   ATTGTGCTCCTTGCGCCAATTCAGTACTTTATTGCTACAAAGTTGGCAGAGGCTCAGAAAAGTACA                   CTTGATTATTCCACTGAGAGACTCAAGAAAACAAATGAAATATTGAAAGGCATCAAACTTCTAAAA                   TTGTATGCCTGGGAACACATTTTCTGCAAAAGTGTGGAGGAAACAAGAATGAAAGAACTATCTAGT                   CTCAAAACCTTTGCACTATATACATCACTCTCCATCTTCATGAATGCAGCAATTCCCATAGAAGCT                   GTTCTTGCTACATTTGTGACCCATGCGTATGCCAGTGGAAAATCAATGAAACCTGCAGAGGCCTTT                   GCTTCACTGTCTCTCTTCCATATCCTGGTCACACCACTGTCCCTGCTCTTCACAATGGTCACATTT                   GCAGTCAAAGCCATCATAAGTGTTCAAAAGCTGAATGAGTTTCTCTTGAGTGATGACATTGGTGAC                   GACAGTTGGCGAACTGGTGAAAGTTCGCTTCCTTTTGAGTCCTGTAAGAAGCACACTGGAGTTCAG                   CCAAAAACTATAAACAGGAAACAGGCCTGGAAGATATCACCTGGACAGCTATGAGCAATAACACGG                   CGTCTACGTCCCGCAGAAACAGAGGACATTGCAATAAAAGGTCACAATGGATACTTTTCATGGGGC                   AGTGGTTTAGCTACATTATCCAATATAGATATTCGAATTCCAACAGGTCAGTTAACCATGATTGTG                   GGCCAAGTACGATGTGGGAAGTCCTCTCTTCTCCTTGCCATCCTCGGTGAGATGCAGACATTAAAA                   GGAAAAGTTCACTGGAGCAATGTAAATGAATCTGAGCCTTCTTTTGAAGCAACCAGAAGTAGGAAC                   AGGTACTCTGTGGCATATGCAGCTCAAAAGCCTTGGCTATTAAATGCTACAGTAGAAGAAAATATT                   ACTTTTGGAAGTCCTTTTAACAAACAGAGGTACAAAGCTGTCACAGATGCCTGTTCTCTTCAGCCA                   GATATTGACTTATTACCATTTGGACATCAAACTGAAATTGGAGAGAGGGGCATCAACCTGAGTGGG                   GGACAGAGGCAGAGAATCTGTGTGGCACGAGCGCTGTATCAAAACACCAACATTGTCTTTTTGGAT                   GATCCATTCTCAGCCCTGGACATTCACTTGAGTGATCATTTAATGCAGGAGGGGATTTTGAAATTC                   CTGCAAGATGACAAAAGGACACTCGTTCTTGTGACTCACAAATTAAAGTATCTGACGCATGCTGAC                   TGGATCATAGCCATGAAAGATGGAAGTGTCCTAAGAGAAGGAACTTTGAAGGACATTCAAACCAAA                   GATGTTGAGCTTTATGAACACTGGAAAACACTTATGAATCGGCAAGATCAAGAATTAGAAAAGGAT                   ATGGAAGCTGACCAAACTACTTTAGAGAGGAAAACTCTCCGACGGGCCATGTATTCAAGAGAAGCC                   AAGCCCAGATGGAGGACGAAGACGAAGAGAAAAGAAGAGGAGGAAGATGAGGATGATAACATGTCC                   ACTGTAATGAGGCTCAGGACTAAAATGCCATCGAAAACCTGCTAACGCTACCTGACATCTAAAAAA                   TTCTTCCTGCTCATCCTGATGATTTTCTCTAAGCTTTTGAAGCATTCGGTCATTGTAGCTATAGAC                   TATTGGCTGGCCACATGGACATCGGAGTACAGTATAAACAATACTGGAAAAGCTGATCAGACCTAC                   TATGTGGCTGGCTTTAGCATACTCTGTGGAGCAGGCATTTTCCTTTGCCTTGTTACATCCCTCACT                   GTAGAATGGATGGGTCTCACAGCTGCCAAAAATCTTCACCACAACCTTCTCAATAAGATAATCCTT                   GGACCAATAGGTTTTTTGATACCACACCCCTGGGAACTGATTCTCAATCGCTTTTCAGCTGATACT                   AATATCATTGATCAGCACATCCCTCCAACCTTGGAATCTCTAACTCGCTCAAAACTGCTCTGCCTG                   TCTCCCATTGGGATGATTTCTTATGCTACTCCTGTGTTCCTGGTTGCTCTCCTGCCCCTTGGTGTT                   GCCTTTTATTTTATCCAGAAATACTTTCGGGTTGCCTCTAAGGACCTCCAGGAACTCGACGATAGT                   ACCCAGCTCCCTCTGCTCTGTCACTTCTCAGAAACAGCAGAAGGACTCACCACCATTCGAACCTTT                   AGGCATGAAACCAGATTTAAACAACGTATGCTGGAACTGACGGATACAAACAACATTGCCTACTTA                   TTTCTCTCAGCTGCCAACAGATGGCTGGAGGTCAGGACAAATTATCTGAAAGCTTGCATTGTCCTC                   ACTGCATCTATAGCATCCATTAGTGGGTCTTCCAATTCTAAATTAATAAACTTGGGTCTTCTGTAT                   GCACTTACGATAACCAATTATTTGAATTGGGTTGTGAGGAACTTGGCTGACCTGGAGGTCCAGATG                   GGTGCAGTGAAGAAGGTGAACAGTTTCCTGACTATGGAGTCAGAGAACTATGAAGGCACAATGGAT                   CCTTCTCAAGTTCCAGAACATTGGCCACAAGAAGGGGAGATCAAGATACATGATCTGTGTGTCAGA                   TATGAAAATAATCTGAAACCTGTTCTTAAGCACGTCAAGGCTTACATAAATCACCTGGACAAAATG                   GGCATATGTGGTCGCACTGGCAGTGGGAAATCATCGTTATCTCTAACTTTCTTAAGAATAATTGAT                   ATATTTGATGGAAAAATTGTCATTGATGGGATAGACATTTCCAAATTACCACTGCACACACTACGT                   TCTAGACTTTCAATCATTCTGCAGGATCCAATACTATTCAGTGGTTCCATTAGATTTAATTTAGAT                   CCAGAGTGCAAATGCACAGATGACAGACTCTGGGAAGCCTTAGAAATTGCTCAGCTGAAGAATATG                   GTCAAATCTCTACCTGGAGGTCTAGATGCGGTTGTCACTGAAGGTGGGGAGAATTTTAGCGTGGGA                   CAGAGACAGCTATTTTGCCTTGCCAGGGCCTTTGTCCGCAAAAGCAGCATTCTTATTATGGATGAG                   GCAACAGCTTCCATTGACATGGCCACAGAGAATATTTTGCAAAAAGTAGTAATGACAGCCTTTGAA                   GACCGGACCGTGGTGACAATGGCTCACCGTGTCTCTTCTATTATAAATGAAGGCCTTGTTTTAGTC                   TTTTCTGAGGGTATTTTAGTGGAGTGTGATACTGTCCCAAATTTGTTCGCCCACAAGAATGGCCCC                   TTTTCCACTTTGGTGATGACCAACAAG TAG                                           OFR Start: ATG at 1       ORF Stop: TAG at 4648           SEQ ID NO:38   1549 aa   MW at 174257.3 kD                     NOV9a,   MSLSFCGNNISSYNINDGVLQMSCPVDALNLVPHVFLLFITFPILFIGWOSQSSAAQTHAATWLHF       CG154077-01       Protein Sequence   PGHNLRWILTFALLFVHVCEIAEGIVSDSRRESRHLHLFMPAVMGFVATTTSIVYYHNIETSNFPK                   LLLALFLYWVMAFITKTTKLVKYCQSGLDISNLRFCITGMMVILNGLLMAVEINVIRVRRYVFFMN                   PQKVKPPEDLQDLGVRFLQPFVNLLSKATYWWMNTLIISAHKKPIDLRATGKLPIAMRAVTNYVCL                   KDAYEEQKkKDHPNRTPSIWIAAAMYRAFGRPILLSSTFRYLAALLGFAGPLCISGIVQRVNETQN                   GTNNTTGISETLSSKEFLENAYVLAVLLFAALILQRTFLQASYYVTIETGINLRGALLAMIYNKIL                   RLSTSNLSMGEMTLGQINNLVAIETNQLMWFLFLCPNLWAAPVQIIMGVILLYNLLGSSALVGAAV                   IVLLAPIQYFIATKLAEAQKSTLDYSTERLKKTNETLKGIKLLKLYAWEHIFCKSVEETRMKELSS                   LKTFALYTSLSIFMNAAIPIAAVLATFVTHAYASGNNLKPAEAFASLSLFHILVTPLSLLFTAARF                   AVKAIISVQKLNEFLLSDEIGDDSWRTGESSLPFESCKKHTGVQPKTINRKQPGNYHLDSYEQSTR                   RLRPAETEDIAIKVTNGYFSWGSGLATLSNIDIRIPTGQLTMIVGQVGCGKSSLLLAILGEMQTLE                   GKVHWSNVNESEPSFEATRSRNRYSVAYAAQKPWLLNAAAEENITFGSPFWKQRYKAVTDACSLQP                   DIDLLPFGDQTEIGERGINLSGGQRQRICVARALYQNTNIVFLDDPFSALDIHLSDHLMQEGILKF                   LQDDKRTLVLVTHKLQYLTHADWIIAMKDGSVLREGTLKDIQTKDVELYEHWKTLMNRQDQELEAA                   MEADQTTLERKTLRRAMYSREAKAQMEDEDEEEEEEEDEDDNMSTVMRLRTKMPWKTCWRYLTSSGG                   FFLLILMIFSKLLKHSVIVAIDYWLATWTSEYSThNTGKADQTYYVACFSILCGAGIFLCLVTSLT                   VEWMGLTAAKNLHHNLLNKIILGPIRFFDTTPLGLILNRFSADTNIIDQHIPPTLESLTRSTLLCL                   SAIGMISYATPVFLVALLPLAAAFYFIQKYFRVASAALQELDDSTQLPLLCHPSETAEGLTTIAAF                   RHETRFKQRMLELTDTNNIAYLFLSAANRWLEVRTDYLGACIVLTASIASISGSSNSGLVGLGLLY                   ALTITNYLNWVVRNLADLEVQMGAVKKVNSFLTMESENYEGTMDPSOVPEHWPQEGEIKIHDLCVR                   YENNLKPVLKHVKAYIKPGQKVGICGRTGSGKSSLSLAFFRMVDIFDGKIVIDGIDISKLPLHTLR                   SRLSIILQDPILFSGSIRFNLDPECKCTDDRLWEALEIAQLKNMVKSLPGGLDAAATEAAEWFSVG                   QRQLFCLARAFVRKSSILIMDEATASIDMATENILQKVVMTAFADRTVVTMAHRVSSIMDAGLVLV                   FSEGILVECDTVPNLFAHKNGPFSTLVMTNK                  
 
     [0404] Further analysis of the NOV9a protein yielded the following properties shown in Table 9B.  
               TABLE 9B                       Protein Sequence Properties NOV9a                                        SignalP   Cleavage site between residues 54 and 55       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 0; pos. chg 0; neg. chg 0           H-region: length 16; peak value 4.86           PSG score: 0.46           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −5.02           possible cleavage site: between 48 and 49           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 17                                         INTEGRAL   Likelihood =   −7.59   Transmembrane   31-47           INTEGRAL   Likelihood =   −1.49   Transmembrane   71-87           INTEGRAL   Likelihood =   −1.12   Transmembrane   104-120           INTEGRAL   Likelihood =   −3.72   Transmembrane   130-146           INTEGRAL   Likelihood =   −5.15   Transmembrane   167-183           INTEGRAL   Likelihood =   −1.75   Transmembrane   306-322           INTEGRAL   Likelihood =   −6.95   Transmembrane   353-369           INTEGRAL   Likelihood =   −0.43   Transmembrane   433-449           INTEGRAL   Likelihood =   −7.43   Transmembrane   451-467           INTEGRAL   Likelihood =   −5.04   Transmembrane   540-556           INTEGRAL   Likelihood =   −4.62   Transmembrane   580-596           INTEGRAL   Likelihood =     0.10   Transmembrane   703-719           INTEGRAL   Likelihood =   −3.24   Transmembrane    993-1009           INTEGRAL   Likelihood =   −7.48   Transmembrane   1036-1052           INTEGRAL   Likelihood =   −6.64   Transmembrane   1133-1149           INTEGRAL   Likelihood =   −0.85   Transmembrane   1226-1242           INTEGRAL   Likelihood =   −1.70   Transmembrane   1509-1525           PERIPHERAL   Likelihood =     1.22 (at 1246)                         ALOM score: −7.59 (number of TMSs: 17)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 38           Charge difference: 3.5 C(3.0)-N(−0.5)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt;Caution: Inconsistent mtop result with signal peptide           &gt;&gt;&gt; membrane topology: type 3b           MITDISC: discrimination of mitochondrial targeting seq                                         R content:   0   Hyd Moment (75):   4.83               Hyd Moment (95):   3.17   G content:   1           D/E content:   1   S/T content:   4                         Score: −4.79           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 9.6%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: found           KLPI at 250           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions                                         918   Q   0.59                   919   E   0.64           920   L   0.64           921   E   0.64           922   K   0.64           923   D   0.64           924   M   0.64           925   E   0.64           926   A   0.64           927   D   0.64           928   Q   0.64           929   T   0.64           930   T   0.64           931   L   0.64           932   E   0.64           933   R   0.64           934   K   0.64           935   T   0.64           936   L   0.64           937   R   0.64           938   R   0.64           939   A   0.77           940   M   0.77           941   Y   0.77           942   S   0.77           943   R   0.81           944   E   0.81           945   A   0.81           946   K   0.81           947   A   0.81           948   Q   0.81           949   M   0.81           950   E   0.81           951   D   0.81           952   E   0.81           953   D   0.81           954   E   0.81           955   E   0.81           956   E   0.81           957   E   0.81           958   E   0.81           959   E   0.81           960   E   0.81           961   D   0.81           962   E   0.81           963   D   0.81           964   D   0.81           965   N   0.81           966   M   0.81           967   S   0.81           968   T   0.81           969   V   0.81           970   M   0.81           971   R   0.81           1266   R   0.81           1267   N   0.81           1268   L   0.81           1269   A   0.81           1270   D   0.81           1271   L   0.81           1272   E   0.81           1273   V   0.81           1274   Q   0.81           1275   M   0.81           1276   G   0.81           1277   A   0.81           1278   V   0.81           1279   K   0.81           1280   K   0.81           1281   V   0.81           1282   N   0.81           1283   S   0.81           1284   F   0.81           1285   L   0.81           1286   T   0.81           1287   M   0.81           1288   E   0.81           1289   S   0.81           1290   E   0.81           1291   N   0.81           1292   Y   0.81           1293   E   0.81                         total: 82 residues           Final Results (k = 9/23):           77.8%: endoplasmic reticulum           11.1%: mitochondrial           11.1%: vacuolar           &gt;&gt; prediction for CG154077-01 is end (k = 9)                  
 
     [0405] 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                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV9a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value               ABP52116     Homo sapiens  ABC transporter   1 . . . 1549    1549/1549 (100%)   0.0           ABCC9 protein SEQ ID NO: 68 -   1 . . . 1549    1549/1549 (100%)             Homo sapiens , 1549 aa.           [EP1217066-A1, 26 JUN. 2002]       AAW53602   Rat sulphonylurea receptor SUR2   1 . . . 1549   1493/1549 (96%)   0.0           protein - Rattus sp, 1545 aa.   1 . . . 1545   1517/1549 (97%)           [JP10052275-A, 24 FEB. 1998]       AAM23694   Human EST encoded protein SEQ   425 . . . 1549    1123/1125 (99%)   0.0           ID NO: 1219 -  Homo sapiens , 1125   1 . . . 1125   1123/1125 (99%)           aa. [WO200154477-A2,           02 AUG. 2001]       ABP52115     Homo sapiens  ABC transporter   1 . . . 1549   1055/1582 (66%)   0.0           ABCC8 protein SEQ ID NO: 67 -   1 . . . 1581   1259/1582 (78%)             Homo sapiens , 1581 aa.           [EP1217066-A1, 26 JUN. 2002]       AAR77087   Rat sulphonylurea receptor - Rattus   1 . . . 1549   1048/1588 (65%)   0.0           sp, 1582 aa. [WO9528411-A1,   1 . . . 1582   1254/1588 (77%)           26 OCT. 1995]                  
 
     [0406] In a BLAST search of public sequence databases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9D.  
               TABLE 9D                          Public BLASTP Results for NOV9a                                             Identities/           Protein           Similarities for       Accession       NOV9a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value               O60706   Sulfonylurea receptor 2 -  Homo     1 . . . 1549    1549/1549 (100%)   0.0             sapiens  (Human), 1549 aa.   1 . . . 1549    1549/1549 (100%)       P82451   Sulfonylurea receptor 2 -   1 . . . 1549   1514/1549 (97%)   0.0             Oryctolagus cuniculus  (Rabbit),   1 . . . 1549   1527/1549 (97%)           1549 aa.       Q95J92   Sulphonylurea receptor 2B -   1 . . . 1545   1491/1545 (96%)   0.0             Oryctolagus cuniculus  (Rabbit),   1 . . . 1545   1514/1545 (97%)           1549 aa.       Q63563   Sulfonylurea receptor 2 -  Rattus     1 . . . 1549   1496/1549 (96%)   0.0             norvegicus  (Rat), 1545 aa.   1 . . . 1545   1518/1549 (97%)       P70170   Sulfonylurea receptor 2 -  Mus     1 . . . 1549   1494/1549 (96%)   0.0             musculus  (Mouse), 1546 aa.   1 . . . 1546   1513/1549 (97%)                  
 
     [0407] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9E.  
               TABLE 9E                          Domain Analysis of NOV9a                                     Identities/                   Similarities for       Pfam   NOV9a   the Matched   Expect       Domain   Match Region   Region   Value               ABC_membrane   297 . . . 585   53/298 (18%)   7.8e−33               217/298 (73%)        ABC_tran   698 . . . 888   58/202 (29%)   4.7e−44               144/202 (71%)        ABC_membrane    994 . . . 1266   49/285 (17%)   5.6e−37               195/285 (68%)        ABC_tran   1339 . . . 1522   52/199 (26%)   5.9e−36               135/199 (68%)                   
 
     Example 10  
     [0408] 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:39   941 bp                     NOV10a,     GAC   ATG GAACAGGATAATACAACATTGCTGACAGAGTTTGTTCTCACAGGACTTACATATCAGCCA       CG155759-02       DNA Sequence   GAGTGGAAAATGCCCCTGTTCTTCGTGTTCTTGGTGATCTATCTCATCACTATTGTGTGGAACCTT                   GGTCTGATTGCTCTTATCTCGAATGACCCACAACTTCACATCCCCATGTACTTTTTTCTTGGGAGT                   TTAGCCTTTGTTGATGCTTGGATATCTTCCACAGTAACTCCCAAAATGTTGGTTAATTTCTTGGCC                   AAAAACAGGATGATATCTCTGTCTGAATGCATGATTCAATTTTTTTCCTTTGCATTTGGTGGAACT                   ACAGAATGTTTTCTCTTGGCAACAATGGCATATGATCGCTATGTAGCCATATGCAAACCTTTACTA                   TATCCAGTGATTATGAACAATTCACTATGCATACGGCTGTTAGCCTTCTCATTTTTAGGTGGCTTC                   CTCCATGCCTTAATTCATGAAGTCCTTATATTCAGATTAACCTTCTGCAATTCTAACATAATACAT                   CATTTTTACTGTGATATTATACCACTGTTTATGATTTCCTGTACTGACCCTTCTATTAATTTTCTA                   ATGGTTTTTATTTTGTCTGGCTCAATTCAGGTATTCACCATTGTGACAGTTCTTAATTCTTACACA                   TTTGCTCTTTTCACAATCCTAAAAAAGAAGTCTGTTAGAGGCGTAAGGAAAGCCTTTTCCACCTGT                   GGAGCCCATCTCTTATCTGTCTCTTTATATTATGGCCCACTTATCTTCATCTATTTGCGCCCTGCA                   TCTCCACAAGCAGATGACCAGGATATGATAGACTCTGTCTTTTATACAATCATAATTCCTTTGCTA                   AATCCCATTATCTACAGTCTGAGAAATAAACAAGTAATAGATTCATTCACAAAAATGGTAAAAAGA                   AATGTT TAG   ATTTCATA                                           ORF Start: ATG at 4       ORF Stop: TAG at 931           SEQ ID NO:40   309 aa   Mw at 35396.8 kD                     NOV10a,   MEQDNTTLLTEFVLTGLTYQPEWKMPLFLVFLVIYLITIVWNLGLIALIWNOPQLHIPMYFFLGSL       CG155759-02       Protein Sequence   AFVDAWISSTVTPKMLVNFLAKNRMISLSECMIQFFSFAFGGTTECPLLATMAYDRYVAICKPLLY                   PVIMNNSLCIRLLAPSFLGGFLHALIHEVLIFRLTFCNSNIIHHFYCDIIPLPMTSCTDPSINFLM                   VFILSGSIQVFTIVTVLNSYTFALFTILKKKSVRGVRKAFSTCGAHLLSVSLYYGPLIEMYLRPAS                   PQADDQDMIDSVFYTIIIPLLNPIIYSLPNKQVIDSFTKMVKRNV                                     SEQ ID NO:41   941 bp                     NOV10b,     GAC   ATG GAACAGGATAATACAACATTGCTGACAGAGTTTGTTCTCACAGGACTTACATATCAGCCA       CG155759-01       DNA Sequence   GAGTGGAAAATGCCCCTGTTCTTGGTGTTCTTGGTGATCTATCTCATCACTATTGTGTGGAACCTT                   GGTCTGATTGCTCTTATCTGGAATCACCCACAACTTCACATCCCCATGTACTTTTTTCTTGGGAGT                   TTAGCCTTTGTTGATGCTTGGATATCTTCCACAGTAACTCCCAAAATGTTGGTTAATTTCTTCGCC                   AAAAACAGGATGATATCTCTGTCTGAATGCATGATTCAATTTTTTTCCTTTGCATTTGGTGGAACT                   ACAGAATGTTTTCTCTTGGCAACAATGGCATATGATCGCTATGTAGCCATATGCAAACCTTTACTA                   TATCCAGTGATTATGAACAATTCACTATGCATACGGCTGTTAGCCTTCTCATTTTTAGGTGGCTTC                   CTCCATGCCTTAATTCATGAAGTCCTTATATTCAGATTAACCTTCTGCAATTCTAACATAATACAT                   CATTTTTACTGTGATATTATACCACTGTTTATGATTTCCTGTACTGACCCTTCTATTAATTTTCTA                   ATGGTTTTTATTTTGTCTGGCTCAATTCAGGTATTCACCATTGTGACAGTTCTTAATTCTTACACA                   TTTGCTCTTTTCACAATCCTAAAAAAGAAGTCTGTTAGAGGCGTAAGGAAAGCCTTTTCCACCTGT                   GGAGCCCATCTCTTATCTGTCTCTTTATATTATGGCCCACTTATCTTCATGTATTTGCGCCCTGCA                   TCTCCACAAGCAGATCACCAAGATATGATAGACTCTGTCTTTTATACAATCATAATTCCTTTGCTA                   AATCCCATTATCTACAGTCTGAGAAATAAACAAGTAATAGATTCATTCACAAAAATGGTAAAAAGA                   AATGTT TAG   ATTTCATA                                           ORF Start: ATG at 4       ORF Stop: TAG at 931           SEQ ID NO:42   309 aa   MW at 35396.8 kD                     NOV10b,   MEQNTTLLTEFVLTGLTYQPEWKMPLFLVFLVIVYLITIVWNLGLIALIWNDPQLHIPMYFFLGSL       CG155759-01       Protein Sequence   AFVDAWISSTVTPKMLVNFLAKNRMISLSECMIQFFSFAFGGTTECFLLATMAYDRYVAICKPLLY                   PVIMNNSLCIRLLAFSFLGGFLHALIHEVLIFRLTFCNSNIIHHFYCDIIPLFMISCTDPSINFLM                   VFILSGSIQVFTIVTVLNSYTFALFTILKKKSVRGVRKAFSTCGAHLLSVSLYYGPLIFMYLRPAS                   PQADDQDMIDSVFYTIIIPLLNPIIYSLRNKQVIDSFTKMVKRNV                  
 
     [0409] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 10B.  
               TABLE 10B                          Comparison of NOV10a against NOV10b.                                         Identities/                   Similarities for           Protein   NOV10a Residues/   the Matched           Sequence   Match Residues   Region                       NOV10b   1 . . . 309   309/309 (100%)               1 . . . 309   309/309 (100%)                      
 
     [0410] Further analysis of the NOV10a protein yielded the following properties shown in Table 10C.  
               TABLE 10C                       Protein Sequence Properties NOV10a                                        SignalP   Cleavage site between residues 52 and 53       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 11; pos. chg 0; neg. chg 3           H-region: length 10; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −3.77           possible cleavage site: between 38 and 39           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 5                                         INTEGRAL   Likelihood =   −9.24   Transmembrane    25-41           INTEGRAL   Likelihood =     0.37   Transmembrane    57-73           INTEGRAL   Likelihood =   −2.02   Transmembrane   142-158           INTEGRAL   Likelihood =   −5.79   Transmembrane   196-212           INTEGRAL   Likelihood =   −1.70   Transmembrane   276-292                                 PERIPHERAL   Likelihood =     0.90 (at 173)                         ALOM score: −9.24 (number of TMSs: 5)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 32           Charge difference: 0.5 C(−0.5)-N(−1.0)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt; membrane topology: type 3b           MITDISC: discrimination of mitochondrial targeting seq                                         R content:   0   Hyd Moment (75):   6.20               Hyd Moment (95):   3.11   G content:   0           D/E content:   2   S/T content:   0                         Score: −7.39           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 6.5%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           KKXX-like motif in the C-terminus: VKRN           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           33.3%: endoplasmic reticulum           11.1%: mitochondrial           11.1%: Golgi           11.1%: vacuolar           11.1%: nuclear           11.1%: vesicles of secretory system           11.1%: cytoplasmic           &gt;&gt; prediction for CG155759-02 is end (k = 9)                  
 
     [0411] A search of the NOV10a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10D.  
               TABLE 10D                          Geneseq Results for NOV10a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV10a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value               AAB71190   Human GPCRX protein SEQ ID 56 -   1 . . . 309   309/309 (100%)   e−180             Homo sapiens , 309 aa.   1 . . . 309   309/309 (100%)           [WO200250275-A2, 27 JUN. 2002]       AAU85253   G-coupled olfactory receptor #114 -   1 . . . 309   309/309 (100%)   e−180             Homo sapiens , 314 aa.   6 . . . 314   309/309 (100%)           [WO200198526-A2, 27 DEC. 2001]       AAU95610   Human olfactory and pheromone G   1 . . . 309   309/309 (100%)   e−180           protein-coupled receptor #97 -  Homo     6 . . . 314   309/309 (100%)             sapiens , 314 aa. [WO200224726-A2,           28 MAR. 2002]       AAG72474   Human OR-like polypeptide query   1 . . . 309   309/309 (100%)   e−180           sequence, SEQ ID NO: 2155 -  Homo     6 . . . 314   309/309 (100%)             sapiens , 314 aa. [WO200127158-A2,           19 APR. 2001]       AAG71500   Human olfactory receptor   1 . . . 309   309/309 (100%)   e−180           polypeptide, SEQ ID NO: 1181 -   6 . . . 314   309/309 (100%)             Homo sapiens , 314 aa.           [WO200127158-A2, 19 APR. 2001]                  
 
     [0412] In a BLAST search of public sequence databases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10E.  
               TABLE 10E                          Public BLASTP Results for NOV10a                                             Identities/           Protein           Similarities for       Accession       NOV10a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value               Q8NGV7   Seven transmembrane helix   1 . . . 309    309/309 (100%)   e−179           receptor -  Homo sapiens  (Human),   6 . . . 314    309/309 (100%)           314 aa.       Q8VG48   Olfactory receptor MOR183-1 -   4 . . . 308   232/305 (76%)   e−141             Mus musculus  (Mouse), 309 aa.   4 . . . 308   272/305 (89%)       Q8VEX5   Olfactory receptor MOR183-9 -   1 . . . 309   239/309 (77%)   e−139             Mus musculus  (Mouse), 309 aa.   1 . . . 309   270/309 (87%)       CAD37583   Sequence 195 from Patent   1 . . . 309   241/309 (77%)   e−139           WO0224726 -  Homo sapiens     17 . . . 325    267/309 (85%)           (Human), 325 aa.       Q8NGV6   Seven transmembrane helix   1 . . . 309   241/309 (77%)   e−139           receptor -  Homo sapiens  (Human),   1 . . . 309   267/309 (85%)           309 aa.                  
 
     [0413] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10F.  
               TABLE 10F                          Domain Analysis of NOV10a                                             Identities/                       Similarities for           Pfam   NOV10a   the Matched   Expect           Domain   Match Region   Region   Value                       7tm_1   41 . . . 290    44/271 (16%)   3.6e−22                   174/271 (64%)                      
 
     Example 11.  
     [0414] 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:43   959 bp                     NOV11a,     TCTGAGGCA   ATG AATGGAATGAATCACTCTGTGGTATCAGAATTTGTATTCATGGGACTCACCAAC       CG155882-01       DNA Sequence   TCACGGGAGATTCAGCTTCTACTTTTTGTTTTCTCTTTGTTGTTCTACTTTGCGAGCATGATGGGA                   AACCTTGTCATTGTATTCACTGTAACCATGGATGCTCATCTGCACTCCCCCATGTATTTCCTCCTG                   GCTAACCTCTCAATCATTGATATGGCATTTTGCTCAATTACAGCCCCTAAGATGATTTGTGATATT                   TTCAAGAAGCACAAGGCCATCTCCTTTCGGCGATGTATTACTCAGATCTTCTTTAGCCATGCTCTT                   GGGGGCACTGAGATGGTGCTGCTCATAGCCATGGCCTTTGACAGATACATGGCCATATGTAAACCT                   CTCCACTACCTGACCATCATGAGCCCAAGAATGTGTCTATACTTTTTAGCCACTTCCTCTATCATT                   GGCCTTATCCACTCATTGGTCCAATTAGTTTTTGTGGTAGATTTACCTTTTTGTCGTCCTAATATC                   TTTGACAGTTTTTACTGTGATCTCCCTCGGCTCCTCAGACTTGCCTGTACCAACACCCAAGAACTG                   GAGTTCATGGTCACTGTCAATAGTGGACTCATTTCTGTGGGCTCCTTTGTCTTGCTGGTAATTTCC                   TACATCTTCATTCTGTTCACTGTTTGGAAACATTCTTCTGGTGGTCTAGCCAAGCCCCTCTCTACC                   CTGTCAGCTCATGTCACTGTGGTCATCTTGTTCTTTGGGCCACTGATGTTTTTCTACACATGGCCT                   TCTCCCACATCACACCTGGATAAATATCTTGCTATTTTTGATGCATTTATTACTCCTTTTCTGAAT                   CCAGTTATCTACACATTCAGGAACAAAGACATGAAAGTGGCAATGAGGAGACTGTGCAGTCCTCTT                   GCGCATTTTACAAAGATTTTG TAA   ATGGCTTGGCT                                           ORF Start: ATG at 10       ORF Stop: TAA at 946           SEQ ID NO:44   312 aa   MW at 35368.9 kD                     NOV11a,   MNGMNHSVVSEFVFMGLTNSREIQLLLFVFSLLFYFASMMGNLVIVFTVTMDAHLHSPMYFLLANL       CG155882-01       Protein Sequence   SIIDMAFCSITAPKMICDIFKKHKAISFRGCITQIFFSHALGGTEMVLLIAMAFDRYMAICKPLHY                   LTIMSPRMCLYFLATSSIIGLIHSLVQLVFVVDLPFCGPNIFDSFYCDLPRLLRLACTNTQELEFM                   VTVNSGLISVGSFVLLVISYIFILFTVWKHSSGGLAKALSTLSAHVTVVILFFGPLMFFYTWPSPT                   SHLDKYLAIFDAFITPFLNPVIYTTFRKDMKVAMRRLCSRLAHFTKIL                  
 
     [0415] Further analysis of the NOV11a protein yielded the following properties shown in Table 11B.  
               TABLE 11B                       Protein Sequence Properties NOV11a                                            SignalP analysis:   Cleavage site between residues 42 and 43           PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 11; pos. chg 0; neg. chg 1           H-region: length 9; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −2.35           possible cleavage site: between 37 and 38           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 6                                             INTEGRAL   Likelihood =   −5.20   Transmembrane    25-41               INTEGRAL   Likelihood =   −1.22   Transmembrane    61-77           INTEGRAL   Likelihood =     0.10   Transmembrane   101-117           INTEGRAL   Likelihood =   −5.31   Transmembrane   150-166           INTEGRAL   Likelihood =   −8.81   Transmembrane   205-221           INTEGRAL   Likelihood =   −3.72   Transmembrane   240-256                                     PERIPHERAL   Likelihood =     0.95 (at 270)                                 ALOM score: −8.81 (number of TMSs: 6)               MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 32           Charge difference: 1.0 C( 0.0)-N(−1.0)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt; membrane topology: type 3b           MITDISC: discrimination of mitochondrial targeting seq                                         R content:   1   Hyd Moment(75):   4.78               Hyd Moment(95):   7.90   G content:   2           D/E content:   2   S/T content:   4                             Score: −5.85               Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: KKHK (3) at 87           pat7: none           bipartite: none           content of basic residues: 6.7%           NLS Score: −0.29           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           KKXX-like motif in the C-terminus: FTKI           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           55.6%: endoplasmic reticulum           11.1%: Golgi           11.1%: vacuolar           11.1%: vesicles of secretory system           11.1%: cytoplasmic           &gt;&gt; prediction for CG155882-01 is end (k = 9)                  
 
     [0416] 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                                         ABJ04030   Human G-protein coupled receptor   1 . . . 312   312/312 (100%)   0.0           SEQ ID NO: 126 -  Homo sapiens ,   1 . . . 312   312/312 (100%)           312 aa. [WO200255558-A2,           18 JUL. 2002]       AAU85300   G-coupled olfactory receptor #161 -   1 . . . 312   312/312 (100%)   0.0             Homo sapiens , 312 aa.   1 . . . 312   312/312 (100%)           [WO200198526-A2, 27 DEC. 2001]       AAG71908   Human olfactory receptor   1 . . . 312   312/312 (100%)   0.0           polypeptide, SEQ ID NO: 1589 -   1 . . . 312   312/312 (100%)             Homo sapiens , 312 aa.           [WO200127158-A2, 19 APR. 2001]       AAU24680   Human olfactory receptor   1 . . . 312   312/312 (100%)   0.0           AOLFR179 -  Homo sapiens , 312 aa.   1 . . . 312   312/312 (100%)           [WO200168805-A2, 20 SEP. 2001]       AAU95651   Human olfactory and pheromone G   4 . . . 312   309/309 (100%)   e−179           protein-coupled receptor #138 -   1 . . . 309   309/309 (100%)             Homo sapiens , 309 aa.           [WO200224726-A2, 28 MAR. 2002]                  
 
     [0417] In a BLAST search of public sequence databases, the NOV11a protein was found to have homology to the proteins shown in the BLASTP data in Table 11D.  
               TABLE 11D                          Public BLASTP Results for NOV11a                                         NOV11a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q8NGB8   Seven transmembrane helix   1 . . . 312    312/312 (100%)   e−180           receptor -  Homo sapiens  (Human),   1 . . . 312    312/312 (100%)           312 aa.       CAD37622   Sequence 275 from Patent   4 . . . 312    309/309 (100%)   e−178           WO0224726 -  Homo sapiens     1 . . . 309    309/309 (100%)           (Human), 309 aa.       Q8VF83   Olfactory receptor MOR245-5 -   1 . . . 311   267/311 (85%)   e−155             Mus musculus  (Mouse), 320 aa.   9 . . . 319   287/311 (91%)       Q8VET0   Olfactory receptor MOR245-21 -   1 . . . 311   235/311 (75%)   e−139             Mus musculus  (Mouse), 312 aa.   1 . . . 311   275/311 (87%)       Q8VF10   Olfactory receptor MOR245-20 -   4 . . . 305   220/302 (72%)   e−133             Mus musculus  (Mouse), 317 aa.   1 . . . 302   261/302 (85%)                  
 
     [0418] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11E.  
               TABLE 11E                          Domain Analysis of NOV11a                                             Identities/                   NOV11a   Similarities for           Pfam   Match   the Matched   Expect           Domain   Region   Region   Value                       7tm_1   41 . . . 287   53/268 (20%)   5.2e−26                   169/268 (63%)                       
 
     Example 12.  
     [0419] 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:45   981 bp                      NOV12a,     ATG TTCCCGGAGAACATCCAAGATGTGCTATCTGCGCTGCCCAATCCTGATGACTACTTCCTCCTG       CG159399-01       DNA Sequence   CGCTGGCTCCAAGCTCGGAGCTTTGACCTGCAGAAATCAGAGGACATGCTGAGGAAGCATATGGAG                   TTCCGGAAGCAACAAGACCTCGCCAACATCCTTGCCTGGCAGCCCCCAGAGGTGGTCAGGCTGTAC                   AACGCTAACGGCATATGCGGCCACGACGGTGAGGGCAGCCCTGTCTGGTACCACATTGTGGGAAGC                   CTGGACCCCAAAGGCCTCTTGCTCTCAGCCTCCAAACAGGAGTTGCTCACGGACAGCTTCCGGAGC                   TGCGAGCTGCTCCTGCGGGAGTGTGAGCTGCAGAGTCAGAAGCTGGGGAACAAGGTGGACAAAATC                   ATAGCTATTTTTGGTCTCGAACGGCTGGGCCTGAGGGATCTGTGGAAGCCAGGAATAGAGCTTCTC                   CAGGAGTTTTTCTCAGCACTTGAAGCAAATTACCCTGAGATCTTGAAGAGTTTAATTGTTGTGAGA                   GCCCCCAAGCTATTCGCCGTAGCCTTCAACCTGCTCAAGTCTTACATGAGTGAAGAGACACGCAGG                   AAGGTGGTGATTCTCGGAGACAACTGGAAGCAGGAGCTGACAAAATTCATCAGCCCCGACCAGCTG                   CCCGTGGAGTTTGGGGGGACCATGACTGACCCCGATGGCAACCCCAAGTGCCTGACCAAGATCAAC                   TACGGGGGTGAGGTGCCCAAGAGCTACTACCTGTGCAAGCAGGTGAGGCTGCAGTATGACCACACG                   AGGTCCGTGGGCCGCCGCTCCTCCCTGCAGGTGGAGAACGAGATCCTGTTCCCGGGCTGTGTGCTC                   AGATGTCCTGAGGTTTTACAACACCTACAGCCTGGTTCATTC TAA   ACGCATCAGCTACACCGTGGA                     GGTACTGCTCCCAGACCAAACCTTCATGGAGAAGATGGAGAATTCTAGAAGGCGATT                                         ORF Start: ATG at 1       ORF Stop: TAA at 901           SEQ ID NO:46   300 aa   MW at 34287.3 kD                     NOV12a,   MFRENIQDVLSALPNPDDYFLLRWLQARSFDLQKSEDMLRKHMEFRKQQDLANILAWQPPEVVRLY       CG159399-01       Protein Sequence   NANGICGHDGEGSPVWYHIVGSLDPKCLLLSASKQELLRDSFRSCELLLRECELQSQKLGKKVEKI                   IAIFGLEGLGLRDLWKPGIELLQEFFSALEANYPEILKSLIVVRAPKLFAVAFNLVKSYMSEETRR                   KVVILGDNWKQELTKFISPDQLPVEFGGTMTDPDGNPKCLTKINYGGEVPKSYYLCKQVRLQYEHT                   RSVGRGSSLQVENEILFPGCVLRCPEVLQHLQPGSF                                     SEQ ID NO:47   877 bp                     NOV12b,   ATGTTCCGGGAGAACATCCAAGATGTGCTATCTGCGCTGCCCAATCCTGATGACTACTTCCTCCTG       CG159399-02       DNA Sequence   CGCTGGCTCCGAGCTCGGAGCTTTGACCTGCAAAAATCAGAGGACATGCTGAGGAAGCATATGGAG                   TTCCGCAACCAACAAGACCTGGCCAACATCCTTGCCTCGCAGCCCCCAGAGGTGGTCAGGCTGTAC                   AACGCTAACGGCATATGCGGCCACGACGGTGAGGGCAGCCCTGTCTGGTACCACATTGTGGGAAGC                   CTGGACCCCAAAGGCCTCTTGCTCTCAGCCTCCAAACAGGAGTTGCTCAGGGACAGCTTCCGGAGC                   TGCGAGCTGCTCCTGCGGGAGTGTGAGCTGCAGAGTCACAAGTTTTTCTCAGCACTTGAAGCAAAT                   TACCCTGAGATCTTGAAGAGTTTAATTCTTCTGAGAGCCCCCAAGCTATTCGCCGTAGCCTTCAAC                   CTGGACAAGTCTTACATGAGTGAAGAGACACGCAGGAAGGTGGTGATTCTCGGACACAACTGGAAG                   CAGGAGCTGACAAAATTCATCAGCCCCGACCAGCTGCCCGTGGAGTTTGGGGGGACCATGACTGAC                   CCCGATGGCAACCCCAAGTGCCTGACCAAGATCAACTACGGGGGTGAGGTGCCCAAGAGCTACTAC                   CTGTCCAAGCAGGTGAGGCTGCAGTATGAGCACACGAGGTCCGTGGGCCGCGGCTCCTCCCTGCAG                   GTGGAGAACCAGATCCTGTTCCCGGGCTGTGTGCTCAGATGTCCTGAGGTTTTACAACACCTACAG                   CCTGGTTCATTC TAA   ACGCATCAGCTACACCGTGGAGGTACTGCTCCCACACCAAACCTTCATGGA                       GAAGATGGAGAAATTCTAG                                           ORF Start: ATG at 1       ORF Stop: TAA at 805           SEQ ID NO:48   268 aa   MW at 30756.1 kD                     NOV12b,   MFRENIQDVLSALPNPDDYFLLRWLRARSFDLQKSEDMLRKHMEFRKQQDLPMILAWQPPEVVRLY       CG159399-02       Protein Sequence   NANGICGHDGEGSPVWYHIVGSLDPKGLLLSASKQELLRDSFRSCELLLRECELQSQKFFSALEAN                   YPEILKSLIVVRAPKLFAVAFNLVKSYMSEETRRKVVILGDNWKQELTKFISPDQLPVEFGGTMTD                   PDGNPKCLTKINYGGEVPKSYYLCKQVRLQYEHTRSVGRGSSLQVENEILFPGCVLRCPEVLQHLQ                   PGSF                  
 
     [0420] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 12B.  
               TABLE 12B                          Comparison of NOV12a against NOV12b.                                     NOV12a   Identities/               Residues/   Similarities for           Protein   Match   the Matched           Sequence   Residues   Region                       NOV12b   1 . . . 300   267/300 (89%)               1 . . . 268   268/300 (89%)                      
 
     [0421] Further analysis of the NOV12a protein yielded the following properties shown in Table 12C.  
               TABLE 12C                       Protein Sequence Properties NOV12a                                        SignalP analysis:   No Known Signal Sequence Predicted       PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 8; pos. chg 1; neg. chg 2           H-region: length 8; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −7.14           possible cleavage site: between 29 and 30           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 1           Number of TMS(s) for threshold 0.5: 0           PERIPHERAL Likelihood = 4.93 (at 279)           ALOM score: −1.75 (number of TMSs: 0)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   1   Hyd Moment(75):   15.87           Hyd Moment(95):   13.14   G content:   0           D/E content:   2   S/T content:   0                         Score: −3.96           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 12.3%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           XXRR-like motif in the N-terminus: FREN           none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 89           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           56.5%: cytoplasmic           17.4%: mitochondrial           13.0%: nuclear            8.7%: peroxisomal            4.3%: plasma membrane           &gt;&gt; prediction for CG159399-01 is cyt (k = 23)                  
 
     [0422] A search of the NOV12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12D.  
               TABLE 12D                          Geneseq Results for NOV12a                                         NOV12a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date)   Residues   Region   Value               ABG12687   Novel human diagnostic protein   2 . . . 287   214/286 (74%)   e−128           #12678 -  Homo sapiens , 502 aa.   19 . . . 293    248/286 (85%)           [WO200175067-A2, 11 OCT. 2001]       AAB43188   Human ORFX ORF2952 polypeptide   2 . . . 287   197/286 (68%)   e−122           sequence SEQ ID NO: 5904 -  Homo     19 . . . 304    245/286 (84%)             sapiens , 308 aa. [WO200058473-A2,           05 OCT. 2000]       AAG67024   Rat SPF -  Rattus norvegicus , 403 aa.   2 . . . 287   192/286 (67%)   e−116           [WO200164740-A1, 07 SEP. 2001]   19 . . . 304    232/286 (80%)       ABG61931   Prostate cancer-associated protein   2 . . . 287   191/286 (66%)   e−116           #132 - Mammalia, 403 aa.   19 . . . 304    233/286 (80%)           [WO200230268-A2, 18 APR. 2002]       AAG67025   Human SPF -  Homo sapiens , 403 aa.   2 . . . 287   191/286 (66%)   e−116           [WO200164740-A1, 07 SEP. 2001]   19 . . . 304    233/286 (80%)                  
 
     [0423] In a BLAST search of public sequence databases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12E.  
               TABLE 12E                          Public BLASTP Results for NOV12a                                         NOV12a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9UDX3   WUGSC:H_DJ0539M06.4 protein -   2 . . . 287   227/286 (79%)   e−138             Homo sapiens  (Human), 406 aa.   19 . . . 304    262/286 (91%)       Q8R0F9   Hypothetical 46.1 kDa protein -  Mus     2 . . . 287   201/286 (70%)   e−123             musculus  (Mouse), 403 aa.   19 . . . 304    245/286 (85%)       Q99J08   SEC14-like protein 2 (Alpha-tocopherol   2 . . . 287   194/286 (67%)   e−115           associated protein) (TAP) -  Mus     19 . . . 304    231/286 (79%)             musculus  (Mouse), 403 aa.       P58875   SEC14-like protein 2 (Alpha-tocopherol   2 . . . 287   190/286 (66%)   e−115           associated protein) (TAP) (bTAP) -  Bos     19 . . . 304    234/286 (81%)             taurus  (Bovine), 387 aa (fragment).       Q99MS0   SEC14-like protein 2 (Alpha-tocopherol   2 . . . 287   192/286 (67%)   e−115           associated protein) (TAP) (Supernatant   19 . . . 304    232/286 (80%)           protein factor) (SPF) (Squalene transfer           protein) -  Rattus norvegicus  (Rat), 403           aa.                  
 
     [0424] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12F.  
               TABLE 12F                          Domain Analysis of NOV12a                                             Identities/                   NOV12a   Similarities for           Pfam   Match   the Matched   Expect           Domain   Region   Region   Value                       CRAL_TRIO   44 . . . 227   55/197 (28%)   7.9e−31                   127/197 (64%)                       
 
     Example 13.  
     [0425] 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:49   2034 bp                     NOV13a,     CGGGCGGAGCGGGCATGGTGGGGTGTCGGGGGCCGCAGGCGTAGCGCTCTCGCCCTGGCC   ATG GAG       CG167853-01       DNA Sequence   CGGCCGGCGCCCGGCGAGGTGGTCATGAGCCAAGCCATCCAGCCGGCGCACGCCACTGCGCGCGGC                   GAGCTGAGCGCGGGGCAGCTGCTCAAGTGGATCGACACCACCGCCTGCCTGGCGGCTGAGAAACAT                   GCTGGAGTTTCCTGCGTTACAGCCTCAGTGGATGACATACAGTTTGAGGAGACAGCTAGAGTTGGA                   CAAGTTATAACCATCAAAGCAAAAGTTACTAGAGCATTCAGCACAAGCATGGAGATCAGTATCAAG                   GTCATGGTACAGGATATGCTCACTGGCATTGAGAAGCTTGTTAGTGTGGCTTTCTCCACATTTGTA                   GCCAAACCAGTTGGAAAAGAAAAGATTCATTTAAAACCAGTCACACTTCTAACTGAACAAGATCAT                   GTGGAACATAATCTGGCTGCTGAGAGAAGGAAAGTTCGATTACAACATGAAGATACCTTTAACAAT                   TTAATGAAGGAAAGTAGCAAATTTGATGATCTCATTTTTGATGAAGAGGAAGCAGCGGTTTCCACA                   AGGGGCACCTCCGTTCAGAGCATTGAACTGGTCCTCCCACCCCATGCAAACCATCACGGAAATACA                   TTTGGTGGCCAGATTATGGCGTGGATGGAGACAGTGGCTACTATTTCTGCAAGCCGCCTGTGTTGG                   GCTCATCCCTTTCTGAAGTCCGTAGATATGTTTAGTTCCGGGGAACCATCTACAGTTGGAGATCGT                   CTTGTCTTCACTGCCATTGTCAACAATACATTTCAGACCTGTGTTGAAGTTAAAGTTCGCGTGGAG                   GCCTTTGACTGTCAGGAATGGGCCGAGGGCCGACGGCGTCACATCAACAGTGCTTTTCTCATTTAC                   AATTCTGCTGATGATAAGGAAAATCTCATCACGTTTCCCAGAATCCAACCCATTTCAAAGGATGAT                   TTCAGACGCTATCGGGGAGCTATTGCACGCAAGCGAATTCGCCTAGGCAGAAAATATGTTATTTCC                   CACAAAGAAGAGGTTCCACTTTGCATACACTGGGATATCAGCAAGCAGGCATCCCTGAGTGACAGC                   AATGTGGAGGCCCTCAAAAAACTGGCAGCCAAAAGGGGTTGGGAGGTTACCAGCACTGTGGAAAAG                   ATAAAAATATATACTCTGGAAGAGCATGATGTTTTATCTGTTTCGGTTGAAAAGCACGTGGGAAGT                   CCAGCACATTTGGCTTATCGTCTCTTGTCTGACTTTACAAAGCGACCTTTGTGGGACCCCCATTTT                   GTGTCCTGTGAAGTCATAGACTGGGTGAGTGAAGATGATCAGCTGTATCACATCACCTGTCCTATA                   CTGAATGATGACAAACCCAAAGACTTGGTAGTACTCGTATCACGAAGAAAACCCCTCAAAGATGGT                   AACACTTACACAGTGGCAGTGAAGTCGGTCATTTTGCCATCGGTCCCCCCGTCTCCACAGTACATC                   AGAAGTGAAATCATATGTGCCGGATTTCTCATCCATGCTATTGACAGCAATTCATGCATCGTATCT                   TACTTTAACCATATGTCTGCTAGCATCCTTCCTTACTTTGCTGGAAATCTTGGTGGCTGGTCAAAA                   TCCATTGAAGAAACAGCAGCCTCTTGTATACAGTTCTTAGAGAATCCTCCTGATGATGGGTTTGTA                   AGCACATTT TAA   AGGTCAACTTTCAATTACTGGTAATTTAATTTCCCACTTTTAATTCCAAGCACC                       CTTAGCCCTGACATCTGTCAAGCTTTGGGGCCACAAAATAATTTAATATAACCCTAAGCAAAATGC                       AGTGACGGAGTTAAAAAACAAAATQCATCTTAAGTCAAATACCAGTGATTTGGATTAGCATTAAAA                       GAGCTTTAGAATTCTGTTGTAAGTCATCTGTGGCTCTGCCTCTTCCAGGGGCACAGATAGTGGAAA                       ATTGCCTGTATGCAATACTATGTGTTCTATAAAATGGCATGAATTTAGTTTAAA                                           OFF Start: ATG at 61       ORF Stop: TAA at 1726           SEQ ID NO:50   555 aa   MW at 62049.3 kD                     NOV13a,   MERPAPGEVVMSQAIOPAHATARGELSAGQLLKWIDTTACLAAEKHAGVSCVTASVDDIQFEETAR       CG167853-01       Protein Sequence   VGQVITIKAKVTRAFSTSMEISIKVMVQDMLTGIEKLVSVAFSTFVAKPVGKEKIHLKPVTLLTEQ                   DHVEHNLAAERRKVRLQHEDTFNNLMKESSKFDDLIFDEEEGAVSTRGTSVQSIELVLPPHANHHG                   NTFGGQIMAWMETVATISASRLCWAHPFLKSVDMFKFRGPSTVGDRLVFTAIVNNTFQTCVEVGVR                   VEAFDCQEWAEGRGRHINSAFLIYNSADDKENLITFPRIQPTSKDDFRRYRGAIARKRIRLGRKYV                   ISHKEEVPLCIHWDISKQASLSDSNVEALKKLAAKRGWEVTSTVEKIKIYTLEEHDVLSVWVEKHV                   GSPAHLAYRLLSDFTKRPLWDPHFVSCEVIDWVSEODQLYHITCPILNDDKPKDLVVLVSRRKPLK                   DGNTYTVAVKSVILPSVPPSPQYIRSEIICAGFLIHAIDSNSCIVSYFNHMSASILPYFAGNLGGW                   SKSIEETAASCIQFLENPPDDGFVSTF                  
 
     [0426] Further analysis of the NOV13a protein yielded the following properties shown in Table 13B.  
               TABLE 13B                       Protein Sequence Properties NOV13a                                        SignalP analysis:   No Known Signal Sequence Predicted       PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 8; pos. chg 1; neg. chg 2           H-region: length 14; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −5.41           possible cleavage site: between 20 and 21           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 0.74 (at 490)           ALOM score: 0.74 (number of TMSs: 0)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   1   Hyd Moment(75):   13.80           Hyd Moment(95):   6.39   G content:   1           D/E content:   2   S/T content:   0                         Score: −5.51           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: RRKP (4) at 457           pat7: none           bipartite: RRYRGAIARKRIRLGRK at 312           content of basic residues: 11.2%           NLS Score: 0.27           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           XXRR-like motif in the N-terminus: ERPA           none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           60.9% cytoplasmic           13.0% mitochondrial           13.0% nuclear            8.7% peroxisomal            4.3%: plasma membrane           &gt;&gt; prediction for CG167853-01 is cyt (k = 23)                  
 
     [0427] A search of the NOV13 a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13C.  
               TABLE 13C                          Geneseq Results for NOV13a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV13a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value               AAB95601   Human protein sequence SEQ ID    6 . . . 549   274/548 (50%)    e−142           NO: 18290 -  Homo sapiens , 594 aa.    44 . . . 586   362/548 (66%)           [EP1074617-A2, 07 FEB. 2001]       AAU18380   Human endocrine polypeptide SEQ   325 . . . 549    94/227 (41%)   3e−44           ID No 335 -  Homo sapiens , 246 aa.    12 . . . 238   136/227 (59%)           [WO200155364-A2, 02 AUG. 2001]       AAU20561   Human secreted protein, Seq ID No   325 . . . 497    78/175 (44%)   3e−37           553 -  Homo sapiens , 207 aa.    12 . . . 186   113/175 (64%)           [WO200155326-A2, 02 AUG. 2001]       AAU18487   Human endocrine polypeptide SEQ   325 . . . 497    78/175 (44%)   3e−37           ID No 442 -  Homo sapiens , 207 aa.    12 . . . 186   113/175 (64%)           [WO200155364-A2, 02 AUG. 2001]       ABG06274   Novel human diagnostic   166 . . . 217    51/52 (98%)   2e−22           protein #6265 -  Homo sapiens , 404 aa.   344 . . . 395    52/52 (99%)           [WO200175067-A2, 11 OCT. 2001]                  
 
     [0428] In a BLAST search of public sequence databases, the NOV13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13D.  
               TABLE 13D                          Public BLASTP Results for NOV13a                                             Identities/           Protein           Similarities for       Accession       NOV13a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value                                         Q8WYK0   Cytoplasmic acetyl-CoA hydrolase 1   1 . . . 555   554/555 (99%)   0.0           (EC 3.1.2.1) (CACH-1) (hCACH-1) -   1 . . . 555   555/555 (99%)             Homo sapiens  (Human), 555 aa.       Q9DBK0   Cytoplasmic acetyl-CoA hydrolase 1   5 . . . 553   449/549 (81%)   0.0           (EC 3.1.2.1) (CACH-1) (mCACH-1) -   6 . . . 554   500/549 (90%)             Mus musculus  (Mouse), 556 aa.       Q8R108   RIKEN cDNA 1300004O04 gene -   13 . . . 553    442/541 (81%)   0.0             Mus musculus  (Mouse), 543 aa   1 . . . 541   492/541 (90%)           (fragment).       Q99NB7   Cytoplasmic acetyl-CoA hydrolase 1   5 . . . 553   434/549 (79%)   0.0           (EC 3.1.2.1) (CACH-1) (rACH) -   6 . . . 554   491/549 (89%)             Rattus norvegicus  (Rat), 556 aa.       Q8VHQ9   Brown fat inducible thioesterase (EC   6 . . . 549   268/546 (49%)   e−137           3.1.2.-) (BFIT) (Adipose associated   46 . . . 586    353/546 (64%)           thioesterase) -  Mus musculus  (Mouse),           594 aa.                  
 
     [0429] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13E.  
               TABLE 13E                          Domain Analysis of NOV13a                                             Identities/                   NOV13a   Similarities for           Pfam   Match   the Matched   Expect           Domain   Region   Region   Value                       Acyl-    1 . . . 122   35/147 (24%)   4.8e−11           CoA —         89/147 (61%)           hydro           Acyl-   165 . . . 304   35/147 (24%)   4.1e−09           CoA —         86/147 (59%)           hydro           START   348 . . . 549   40/250 (16%)   0.3                   122/250 (49%)                       
 
     Example 14.  
     [0430] 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:51   1583 bp                     NOV14a,     GGCTGAGAGCGCGCC   ATG GGGCAGGCCGGCTGCAAGGGGCTCTGCCTGTCGCTGTTCGACTACAAG       CG167873-01       DNA Sequence   ACCGAGAAGTATGTCATCGCCAAGAACAACAAGGTGCGCCTGCTGTACCGGCTGCTGCAGGCCTCC                   ATCCTGGCGTACCTGGTCGTATGGGTGTTCCTGATAAAGAAGGGTTACCAAGACGTCGACACCTCC                   CTGCAGAGTGCTGTCATCACCAAAGTCAAGGGCGTGGCCTTCACCAACACCTCGGATCTTGGGCAG                   CGGATCTGGGATGTCGCCGACTACGTCATTCCAGCCCAGGGAGAGAACGTCTTTTTTGTGGTCACC                   AACCTGATTGTGACCCCCAACCAGCGGCAGAACGTCTGTGCTGAGAATGAAGCCATTCCTGATGGC                   GCGTGCTCCAAGGACAGCGACTGCCACGCTCGGGAAGCGGTTACAGCTGGAAACGGAGTGAAGACC                   CGCCGCTGCCTGCGGAGAGAGAACTTCGCCAGGGGCACCTGTGAGATCTTTGCCTGGTGCCCGTTG                   GAGACAAGCTCCAGGCCCGAGGAGCCATTCCTGAAGGAGGCCGAAGACTTCACCATTTTCATAAAG                   AACCACATCCGTTTCCCCAAATTCAACTTCTCCAACCGTCTCGACAATAAACTTTCAAAGTCTGTC                   TCCTCCGGGTACAACTTCAGATTTGCCAGATATTACCGAGACGCAGCCGGGGTGGAGTTCCGCACC                   CTGATGAAAGCCTACGGGATCCGCTTTGACGTGATGGTGAACGGCAAGGGTGCTTTCTTCTGCGAC                   CTGGTACTCATCTACCTCATCAAAAAGAGAGAGTTTTACCGTGACAAGAAGTACGAGGAAGTGAGG                   GGCCTAGAAGACAGTTCCCAGGAGGCCGAGGACGAGGCATCGGGGCTGGGGCTATCTGAGCAGCTC                   ACATCTGGGCCAGGGCTGCTGGGGATGCCGGAGCAGCAGGAGCTGCAGGAGCCACCCGAGGCGAAG                   CGTGGAAGCAGCAGTCAGAAGGGGAACGGATCTGTGTGCCCACAGCTCCTGGAGCCCCACAGGAGC                   ACG TGA   ATTGCCTCTGCTTACGTTCAGGCCCTGTCCTAAACCCAGCCGTCTAGCACCCAGTGATCC                       CATGCCTTTGGGAATCCCAGGATGCTGCCCAACGCGAAATTTGTACATTGGGTGCTATCAATGCCA                       CATCACAGGGACCAGCCATCACAGAGCAAACTGACCTCCACGTCTGATGCTCGGGTCATCAGGACG                       GACCCATCATGGCTGTCTTTTTGCCCCACCCCCTGCCGTCAGTTCTTCCTTTCTCCGTGGCTGGCT                       TCCCGCACTAGGGAACGGGTTGTAAATGGGGAACATGACTTCCTTCCGGAGTCCTTGAGCACCTCA                       GCTAAGGACCGCAGTGCCCTCTAGAGTTCCTAGATTACCTCACTGGGAATAGCATTGTGCGTGTCC                       GGAAAAGGGCTCCATTTGGTTCCAGCCCACTCCCCTCTGCAAGTCCCACAGCTTCCCTCAGAGCAT                       ACTCTCCAGTGGATCCAAGTACTCTCTCTCCTAAAGACACCACCTTCCTGCCAGCTGTTTGCCCT                                           ORF Start: ATG at 16       ORF Stop: TGA at 1060           SEQ ID NO:52   348 aa   MW at 38876.9 kD                     NOV14a,   MGQACCKGLCLSLFDYKTEKYVIAKNKKVGLLYRLLQASILAYLVVWVFLIKKGYQDVDTSLQSAV       CG167873-01       Protein Sequence   ITKVKGVAFThTSDLGQRIWDVADYVIPAQGENVFFVVTNLIVTPNQRQNVCAENEGIPDGACSKD                   SDCHAGEAVTAGNOVKTGRCLRRENLARGTCEIFAWCPLETSSRPEEPFLKEAEDFTIFIKNHIRF                   PKFNFSNRLDNKLSKSVSSGYNFRFARYYRDAAGVEFRTLMKAYGIRFDVMVNGKGAFFCDLVLIY                   LIKKREFYRDKKYEEVRGLEDSSQEAEDEASGLCLSEQLTSGPGLLGMPEQQELQEPPEAKRGSSS                   QKGNGSVCPQLLEPHRST                                     SEQ ID NO:53   1616 bp                     NOV14b,     GGCACGAGGGTCCGCAAGCCCGGCTGAGAGCGCGCC   ATG CGGCAGGCGGGCTGCAAGGGGCTCTGC       CG167873-02       DNA Sequence   CTGTCGCTGTTCGACTACAAGACCGAGAAGTATGTCATCGCCAAGAACAAGAAGGTGGGCCTGCTG                   TACCGGCTGCTGCAGGCCTCCATCCTGGCGTACCTGGTCGTATGGGTGTTCCTGATAAAGAAGGGT                   TACCAAGACGTCGACACCTCCCTGCAGAGTGCTGTCATCACCAAAGTCAAGGGCCTGGCCTTCACC                   AACACCTCGGATCTTGGGCAGCGGATCTGGGATGTCGCCGACTACGTCATTCCAGCCCAGGGAGAG                   AACGTCTTTTTTGTGGTCACCAACCTGATTGTGACCCCCAACCAGCGGCAGAACGTCTGTGCTGAG                   AATGAAGGCATTCCTGATCGCGCGTGCTCCAAGGACAGCGACTGCCACGCTGGGGAAGCGGTTACA                   GCTGGAAACGGAGTGAAGACCGGCCGCTGCCTGCGGAGACGGAACTTGGCCAGGGGCACCTGTGAG                   ATCTTTGCCTGGTGCCCGTTGGAGACAAGCTCCAGGCCGGAGGAGCCATTCCTGAAGGAGGCCGAA                   GACTTCACCATTTTCATAAAGAACCACATCCGTTTCCCCAAATTCAACTTCTCCAACAATCTGATG                   GACGTCAACGACAGATCTTTCCTGAAATCATGCCACTTTGGCCCCAAGAACCACTACTGCCCCATC                   TTCCGACTGGGCTCCGTGATCCGCTGGGCCGGGAGCGACTTCCAGGATATAGCCCTGGAGATTTGC                   CAGATATTACCGAGACGCAGCCGGGGTGGAGTTCCGCACCCTGATGAAAGCCTACGGGATCCGCTT                     TGA   CGTGATGGTGAACGGCAAGGCAGGGAAGTTCAGCATCATTCCCACCATCATCAACGTGGGCTC                       TGCGGTGGCGCTCATGGGTGCTGGTGCTTTCTTCTGCGACCTGGTACTCATCTACCTCATCAAAAA                       GAGAGAGTTTTACCGTGACAAGAAGTACGAGGAAGTGAGGGGCCTAGAAGACAGTTCCCAGGAGGC                       CGAGGACGAGGCATCGGGGCTGGGGCTATCTGAGCAGCTCACATCTGGGCCAGGGCTGCTGGGGAT                       GCCGGAGCAGCAGGAGCTGCAGGAGCCACCCGAGGCGAAGCGTGGAAGCAGCAGTCAGAAGGGGAA                       CGGATCTGTGTGCCCACAGCTCCTGGAGCCCCACAGGAGCACGTGAATTGCCTCTGCTTACGTTCA                       GGCCCTGTCCTAAACCCAGCCGTCTAGCACCCAGTGATCCCATGCCTTTGGGAATCCCAGGATGCT                       GCCCAACGGGAAATTTGTACATTGGGTGCTATCAATGCCACATCACAGGGACCAGCCATCACAGAG                       CAAAGTGACCTCCACGTCTGATGCTGGGGTCATCAGGACGGACCCATCATGGCTGTCTTTTTGCCC                       CACCCCCTGCCGTCAGTTCTTCCTTTCTCCGTGGCTGGCTTCCCGCACTAGGGAACGGGTTGTAAA                       TGGGGAACATGACTTCCTTCCGGAGTCCTTGAGCACCTCAGCTAAGGACCGCAGTGCCCTGTAGAG                       TTCCTAGATTACCTCACTGGGAATAGCATTGT                                           ORF Start: ATG at 37       ORF Stop: TGA at 859           SEQ ID NO:54   274 aa   MW at 30600.8 kD                     NOV14b,   MGQAGCKGLCLSLFDYKTEKYVIAKNKKVGLLYRLLQASILAYLVVWVFLIKKGYQDVDTSLQSAV       CG167873-02       Protein Sequence   ITKVKGVAFTNTSDLGQRIWDVADYVIPAQGENVFFVVTNLIVTPNQRQNVCAENEGIPDGACSKD                   SDCHAGEAVTAGNGVKTGRCLRRGNLARGTCEIFAWCPLETSSRPEEPFLKEAEDFTIFIKNHIRF                   PKFNFSNWVMDVKDRSFLKSCHFGPKNHYCPIFRLGSVIRWAGSDFQDIALEICQILPRRSRGGVP                   HPDESLRDPL                  
 
     [0431] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 14B.  
               TABLE 14B                          Comparison of NOV14a against NOV14b.                                         Identities/                   Similarities for           Protein   NOV14a Residues/   the Matched           Sequence   Match Residues   Region                       NOV14b   1 . . . 227   207/227 (91%)               1 . . . 227   212/227 (93%)                      
 
     [0432] Further analysis of the NOV14a protein yielded the following properties shown in Table 14C.  
               TABLE 14C                       Protein Sequence Properties NOV14a                                        SignalP analysis:   Cleavage site between residues 57 and 58       PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 7; pos. chg 1; neg. chg 0           H-region: length 7; peak value 3.40           PSG score: −1.00           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −6.29           possible cleavage site: between 41 and 42           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 1           Number of TMS(s) for threshold 0.5: 1                                     INTEGRAL   Likelihood =   −7.22   Transmembrane 35-51                                 PERIPHERAL   Likelihood =     0.63 (at 250)                         ALOM score: −7.22 (number of TMSs: 1)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 42           Charge difference: −5.0 C(0.0)-N(5.0)           N &gt;= C: N-terminal side will be inside           &gt;&gt;&gt; membrane topology: type 2 (cytoplasmic tail 1 to 35)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   0   Hyd Moment(75):   7.02           Hyd Moment (95):   8.95   G content:   3           D/E content:   2   S/T content:   2                         Score: −7.41           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 12.9%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type1: none           type2: none           NMYR: N-myristoylation pattern: MGQAGCK           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: 15, 20, 32           Dileucine motif in the tail: found LL at 31           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 89           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           34.8%: cytoplasmic           26.1%: mitochondrial           17.4%: Golgi            8.7%: endoplasmic reticulum            4.3%: extracellular, including cell wall            4.3%: nuclear            4.3%: vesicles of secretory system           &gt;&gt; prediction for CG167873-01 is cyt (k = 23)                  
 
     [0433] 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 14D.  
               TABLE 14D                          Geneseq Results for NOV14a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV14a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value               ABB97440   Novel human protein SEQ ID NO:   1 . . . 348   255/422 (60%)    e−120           708 -  Homo sapiens , 422 aa.   1 . . . 422   270/422 (63%)           [WO200222660-A2, 21 MAR. 2002]       AAW76439   Human p53 regulated protein, P2X5 -   1 . . . 210   159/214 (74%)   1e−91             Homo sapiens , 455 aa.   1 . . . 214   181/214 (84%)           [WO9842835-A1, 01 OCT. 1998]       AAE01141   Human purinergic receptor P2X6   13 . . . 204    102/192 (53%)   3e−54           protein -  Homo sapiens , 441 aa.   22 . . . 212    131/192 (68%)           [US6214581-B1, 10 APR. 2001]       AAB84382   Amino acid sequence of a human   6 . . . 206   110/204 (53%)   3e−54           purinoreceptor P2X4 -  Homo sapiens ,   5 . . . 203   141/204 (68%)           388 aa. [US6242216-B1,           05 JUN. 2001]       AAW55035   HPURR amino acid sequence -  Homo     6 . . . 206   110/204 (53%)   3e−54             sapiens , 388 aa. [WO9818916-A1,   5 . . . 203   141/204 (68%)           07 MAY 1998]                  
 
     [0434] In a BLAST search of public sequence databases, the NOV14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14E.  
               TABLE 14E                          Public BLASTP Results for NOV14a                                             Identities/           Protein           Similarities for       Accession       NOV14a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value               Q93086   P2X purinoceptor 5 (ATP receptor)   1 . . . 348   264/421 (62%)   e−126           (P2X5) (Purinergic receptor) -  Homo     1 . . . 421   280/421 (65%)             sapiens  (Human), 421 aa.       AAH39015   Similar to purinergic receptor P2X,   1 . . . 348   263/422 (62%)   e−125           ligand-gated ion channel, 5 -  Homo     1 . . . 422   278/422 (65%)             sapiens  (Human), 422 aa.       CAD34956   Sequence 264 from Patent   1 . . . 348   255/422 (60%)   e−119           WO0222660 -  Homo sapiens     1 . . . 422   270/422 (63%)           (Human), 422 aa.       Q91VE2   ATP-gated ionotropic P2X5 receptor   1 . . . 204   157/204 (76%)   3e−92            subunit (P2X purinoceptor) (ATP   1 . . . 204   181/204 (87%)           receptor) (Purinergic receptor) -  Mus               musculus  (Mouse), 455 aa.       S71344   purinergic receptor P2X5 - rat, 455 aa.   1 . . . 210   160/214 (74%)   5e−92                1 . . . 214   182/214 (84%)                  
 
     [0435] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14F.  
               TABLE 14F                          Domain Analysis of NOV14a                                             Identities/                   NOV14a   Similarities for           Pfam   Match   the Matched   Expect           Domain   Region   Region   Value                       P2X —     14 . . . 204   139/208 (67%)   8.8e−150           receptor       190/208 (91%)           P2X —     205 . . . 292     62/112 (55%)    5e−52           receptor        87/112 (78%)                      
 
     Example 15.  
     [0436] 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:55   1596 bp                     NOV15a,     GGGGAACCCCAGGCCGCCGGCGCCCGGACC   ATG TCGTCTCCGGGGCCGTCGCAGCCGCCGGCCGAG       CG167893-01       DNA Sequence   GACCCGCCCTGGCCCGCCCGCCTCCTGCGTGCGCCTCTGGCGCTGCTGCGGCTCGACCCCAGCGGG                   GGCGCGCTGCTGCTATGCGGCCTCGTAGCGCTGCTGGGCTGGAGCTGGCTGCGGAGCCGCCGGGCG                   CGGGGCATCCCGCCCGGGCCCACGCCCTGGCCTCTGGTGGGCAACTTCGGTCACGTGCTGCTGCCT                   CCCTTCCTCCGGCGGCGGAGCTGGCTGAGCAGCAGGACCAGGGCCGCAGGGATTGATCCCTCGGTC                   ATAGGCCCGCAGGTGCTCCTGGCTCACCTAGCCCGCGTGTACGGCAGCATCTTCAGCTTCTTTATC                   GGCCACTACCTGGTCGTGGTCCTCAGCGACTTCCACAGCGTGCGCGAGGCGCTGGTGCAGCAGGCC                   GACGTCTTCAGCGACCGCCCGCGGGTGCCGCTCATCTCCATCGTGACCAAGGAGAAGGGTGTTGTG                   TTTGCACATTATGGTCCCGTCTGGAGACAACAAAGGAAGTTCTCTCATTCAACTCTTCGTCATTTT                   GGGTTGGGAAAACTTAGCTTGGAGCCCAAGATTATTGAGGAGTTCAAATATGTGAAAGCAGAAATG                   CAAAAGCACGGAGAAGACCCCTTCTGCCCTTTCTCCATCATCAGCAATGCCGTCTCTAACATCATT                   TGCTCCTTGTGCTTTGGCCAGCGCTTTGATTACACTAATAGTGAGTTCAAGAAAATGCTTGGTTTT                   ATGTCACGAGGCCTAGAAATCTGTCTGAACAGTCAAGTCCTCCTGGTCAACATATGCCCTTGGCTT                   TATTACCTTCCCTTTGGACCATTTAAGGAATTAAGACAAATTGAAAAGGATATAACCAGTTTCCTT                   AAAAAAATCATCAAAGACCATCAAGAGTCTCTGGATAGAGAGAACCCTCAGGACTTCATAGACATG                   TACCTTCTCCACATGGAAGAGGAGAGGAAAAATAATAGTAACAGCAGTTTTGATGAAGAGTACTTA                   TTTTATATCATTGGGGATCTCTTTATTGCTGGGACTGATACCACAACTAACTCTTTGCTCTGGTGC                   CTGCTGTATATGTCGCTGAACCCCGATGTACAAGAAAAGGTTCATGAAGAAATTGAAAGAGTCATT                   GGCGCCAACCGAGCTCCTTCCCTCACAGACAAGGCCCAGATGCCCTACACAGAAGCCACCATCATG                   GAAGTGCAGAGGCTAACTGTGGTGGTGCCGCTTGCCATTCCTCATATGACCTCAGAGAACACAGTG                   CTCCAAGGGTATACCATTCCTAAACGCACATTGATCTTACCCAACCTGTGGTCAGTACATAGAGAC                   CCAGCCATTTGGGAGAAACCGGAGGATTTCTACCCTAATCGATTTCTGGATGACCAAGGACAACTA                   ATTAAAAAAGAAACCTTTATTCCTTTTGGGATAGGTCAGTTAGCCTTTACATTTTACATATATATG                   TGTGTGTGTGTGTGTGTGTGTGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTATAGTTGAATGAA                     TGCGTGAATAAA                                           ORF Start: ATG at 31       ORF Stop: TAG at 1573           SEQ ID NO:56   514 aa   MW at 58488.5 kD                     NOV15a,   MSSPGPSQPPAEDPPWPARLLRAPLGLLRLDPSGGALLLCGLVALLGWSWLRRRRARGIPPGPTPW       CG167893-01       Protein Sequence   PLVGNFGHVLLPPFLRRRSWLSSRTRAAGIDPSVIGPQVLLAHLARVYGSIFSFFIGHYLVVVLSD                   FHSVREALVQQAEVFSDRPRVPLISIVTKEKGVVFAHYGPVWRQQRKFSHSTLRHFGLGKLSLEPK                   IIEEFKYVKAEMQKHCEDPFCPFSIISNAVSNIICSLCFGQRFDYTNSEFKKMLGFMSRGLEICLN                   SQVLLVNICPWLYYLPFGPFKELRQIEKDITSFLKKIIKDHQESLDRENPQDFIDMYLLHMEEERK                   NNSNSSFDEEYLFYIIGDLFIAGTDTTTNSLLWCLLYMSLNPDVQEKVHEEIERVIGANRAPSLTD                   KAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAIWEKPEDF                   YPNRFLDDQGQLIKKETFIPFGIGQLAFTFYIYMCVCVCVCVCVCVCVCVCV                  
 
     [0437] Further analysis of the NOV15a protein yielded the following properties shown in Table 15B.  
               TABLE 15B                       Protein Sequence Properties NOVl5a                                        SignalP analysis:   Cleavage site between residues 59 and 60       PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 0; pos. chg 0; neg. chg 0           H-region: length 11; peak value 0.89           PSG score: −3.51           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −0.09           possible cleavage site: between 51 and 52           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 4                                         INTEGRAL   Likelihood =    −3.29   Transmembrane    35-51           INTEGRAL   Likelihood =    −1.86   Transmembrane   117-133           INTEGRAL   Likelihood =    −0.69   Transmembrane   221-237           INTEGRAL   Likelihood =   −16.40   Transmembrane   498-514                                 PERIPHERAL   Likelihood =      1.32 (at 405)                         ALOM score: −16.40 (number of TMSs: 4)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 42           Charge difference: 3.0 C(5.0)-N(2.0)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt; membrane topology: type 3b           MITDISC: discrimination of mitochondrial targeting seq                                         R content:   0   Hyd Moment (75):   3.90               Hyd Moment (95):   2.10   G content:   1           D/E content:   2   S/T content:   3                         Score: −7.39           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: RRRR (5) at 52           pat7: PPFLRRR (3) at 78           pat7: PFLRRRS (4) at 79           bipartite: none           content of basic residues: 10.1%           NLS Score: 0.44           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: found           ILPN at 442           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif; none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DMA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           33.3%: vacuolar           33.3%: endoplasmic reticulum           11.1%: mitochondrial           11.1%: Golgi           11.1%: cytoplasmic           &gt;&gt; prediction for CG167893-01 is vac (k = 9)                  
 
     [0438] 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                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV15a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value                                         AAU91320   Human P450TEC protein -  Homo     1 . . . 487   486/487 (99%)   0.0             sapiens , 544 aa. [WO200181585-A2,   1 . . . 487   487/487 (99%)           01 NOV. 2001]       AAE21061   Human drug metabolising enzyme   1 . . . 487   486/487 (99%)   0.0           (DME-19) protein -  Homo sapiens ,   1 . . . 487   487/487 (99%)           544 aa. [WO200212467-A2,           14 FEB. 2002]       ABB55770   Human polypeptide SEQ ID NO 146 -   164 . . . 487    323/324 (99%)   0.0             Homo sapiens , 398 aa.   18 . . . 341    324/324 (99%)           [US2001039335-A1, 08 NOV. 2001]       AAU39061   Human secreted protein yb44_1 -   164 . . . 487    323/324 (99%)   0.0             Homo sapiens , 398 aa.   18 . . . 341    324/324 (99%)           [WO200175068-A2, 11 OCT. 2001]       AAY29335   Human secreted protein clone yb44_1   164 . . . 487    323/324 (99%)   0.0           protein sequence -  Homo sapiens , 398   18 . . . 341    324/324 (99%)           aa. [WO9937674-A1, 29 JUL. 1999]                  
 
     [0439] In a BLAST search of public sequence databases, the NOV15a protein was found to have homology to the proteins shown in the BLASTP data in Table 15D.  
               TABLE 15D                          Public BLASTP Results for NOV15a                                         NOV15a   Identities/           Protein       Residues/   Similarities       Accession       Match   for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value               CAD12288   Sequence 16 from Patent   1 . . . 487   486/487 (99%)   0.0           WO0181585 -  Homo sapiens     1 . . . 487   487/487 (99%)           (Human), 544 aa.       Q9CX98   8430436A10Rik protein -  Mus     1 . . . 512   392/512 (76%)   0.0             musculus  (Mouse), 501 aa.   1 . . . 497   436/512 (84%)       Q96EQ6   Similar to RIKEN cDNA   1 . . . 163    163/163 (100%)   1e-91           8430436A10 gene -  Homo sapiens     1 . . . 163    163/163 (100%)           (Human), 168 aa.       Q8JHT9   Cytochrome P450 -  Brachydanio     25 . . . 486    179/464 (38%)   5e-87             rerio  (Zebrafish)   3 . . . 436   271/464 (57%)           ( Danio rerio ), 498 aa.       Q9PVI0   Cytochrome P450 2N1 -  Fundulus     36 . . . 487    182/454 (40%)   2e-85             heteroclitus  (Killifish)   14 . . . 441    263/454 (57%)           (Mummichog), 497 aa.                  
 
     [0440] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15E.  
               TABLE 15E                          Domain Analysis of NOV15a                                             Identities/                       Similarities           Pfam   NOV15a Match   for the   Expect           Domain   Region   Matched Region   Value                       p450   60 . . . 72     9/13 (69%)   0.21                     13/13 (100%)           p450   107 . . . 486   150/413 (36%)   6.4e-132                   302/413 (73%)                      
 
     Example 16.  
     [0441] 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:57   3853 bp                     NOV16a,     CGCCTGTCCCTAGCTGTGGCTGAGCCAAGATTGCACTTGTGAGAAGGCCTGACACGCAGC   ATG GGC       CG169088-01       DNA Sequence   CACATGGCCAATAGTTCCATCGAGTTCCACCCCAAGCCCCAGCAGCAGCGGGATGTCCCCCAGGCT                   GGAGGCTTTGGGTGCACGCTGGCGGAGCTGCGCACCCTCATGGAGCTGCGAGCGGCCGAGGCGCTG                   CAGAAGATCGAGGACGCCTACGGGGATGTCAGCGGGCTCTGCCGGAGGCTGAAGACCTCACCCACA                   GAGGGCCTGCCGGACAACACCAATGACCTGGAGAAGCGCAGGCAGATCTACGGGCAGAACTTCATC                   CCCCCAAAGCAACCCAAGACCTTCCTGCAGCTGGTGTGGGAGGCCCTGCAGGACGTGACCCTCATC                   ATCCTGGAGGTGGCTGCCATCGTCTCTCTGGGCCTCTCGTTCTATGCGCCGCCAGGAGAGGAGAGT                   GAAGCCTGTGGGAATGTGTCGCGAGGCGCAGAAGATGAGGGCGAGGCCGAAGCTGGCTGGATCGAG                   GGGGCTGCCATCCTGCTGTCCGTCATCTGTGTGGTGCTGGTCACGGCCTTCAATGACTGGAGCAAG                   GAGAAGCAGTTCCGAGGCCTGCAGAGCCGAATTGAGCAGGAGCAGAAGTTCACGGTCATCCGGAAC                   GGGCAGCTCCTCCAGGTCCCCGTGGCTGCGCTGGTGGTGGGGGACATTGCCCAGGTCAAGTACGGC                   GACCTGCTGCCAGCCGACGGCGTGCTCATCCAGGCCAATGACCTCAAGATCCACGAGAGCTCCCTG                   ACGGGCGAGTCTGACCACGTGCGCAAGTCAGCTGACAAAGATCCCATGCTGCTCTCAGGCACTCAT                   GTCATCGAAGGTTCTGGAAGAATGGTGGTGACCGCCGTTGGCGTGAATTCCCAGACAGGCATCATC                   TTCACGCTGCTTGGAGCTGGCGGAGAGGAGGAAGAGAAGAAAGATAAGAAAGGCAAGCAGCAGGAT                   GGGGCCATGCAGAGTAGCCAGACCAAAGCTAAGAAGCAGGATGGTGCAGTGGCCATGGAGATGCAG                   CCCCTGAAGAGCGCGGAGGGTGGGGAGATGGAGGAGCGGGAGAAGAAGAAAGCCAACGCACCCAAA                   AAGGAGAAGTCTGTCCTTCAGGGGAAGCTCACAAAGCTAGCCGTGCAGATCGGGAAAGCAGGGCTG                   GTGATGTCTGCCATCACCGTCATCATCCTGGTCCTCTACTTTGTGATTGAGACGTTTGTCGTGGAA                   GGCCGGACATGGCTGGCAGAGTGCACGCCGGTCTATGTACAATACTTCGTGAAGTTCTTCATCATT                   GGTGTCACTGTGCTGGTCGTGGCTGTCCCAGAGGGCCTGCCTCTTGCTGTCACCATCTCCTTAGCT                   TACTCTGTCAAGAAAATGATGAAAGACAACAACCTGGTGCGCCACCTGGATGCCTGCGAGACCATG                   GGCAACGCCACAGCCATCTGCTCCGACAAGACGGGCACGCTCACCACCAACCGTATGACCGTGGTC                   CAGTCCTACCTAGGGGACACCCACTACAAAGAGATTCCGGCCCCCAGCGCCCTGACCCCTAAGATC                   CTCGACCTCCTGGTCCATGCCATCTCCATCAACAGTGCCTATACCACCAAAATACTACCTCCTGAG                   AAGGAAGGCGCCCTCCCACGCCAGGTGGGCAATAAGACGGAGTGCGCCCTGCTGGGCTTCGTCTTG                   GACCTGAAGCGGGACTTCCAGCCCGTGCGCGAGCAGATCCCGGAAGACAAGCTTTACAAAGTGTAC                   ACCTTCAACTCGGTCCGCAAGTCCATGAGCACAGTCATCCGCATGCCCGACGGTGGCTTCCGCCTC                   TTCAGCAAGGGGGCCTCACAGATCCTCTTGAAAAAGTGCACCAACATCTTGAACAGCAATGGCGAA                   CTCCGGGGCTTTCGGCCTCGGGACCGGGACGACATGGTCAGGAAGATCATCGAGCCGATGGCTTGC                   GATGGCCTCCGCACCATCTGCATCGCCTACCGGGACTTCTCTGCAGGCCAGGAGCCCGACTCGGAC                   AACGAGAATGAGGTCGTGGGTGACCTCACCTGCATAGCTGTCGTGGGCATTGAGGACCCTGTGCGG                   CCCGAGGTCCCTGAACCTATCCGAAAATGCCAGCGTGCTGGCATCACAGTCCGCATGGTGACTGGG                   GACAACATCAACACGGCCCGGGCCATCGCAGCCAAATGCGGCATCATCCAGCCCGGGGACGACTTC                   CTGTGCCTAGAAGGGAAGGAGTTCAACCGGCGGATCCGCAATGAGAAAGGCGAGATAGAACACGAG                   CGGCTGGACAAGGTGTGGCCCAAGCTGAGGGTGCTGGCCCGGTCGTCTCCCACCGACAAGCACACA                   CTGGTCAAAGGGATTATCGACAGCACCACTGGTGAGCAGCGGCAGGTGGTCGCTGTGACAGGGGAT                   GGCACCAACGATGGGCCGGCCCTCAAGAAGGCGGACGTGGGCTTCGCCATGGGCATCGCAGGGACC                   GACGTGGCCAAGGAGGCCTCCGACATCATCCTGACCGATGACAACTTCACCAGCATCGTCAAGGCA                   GTCATGTGGGGCCGTAACGTCTATGACAGCATCTCCAAGTTCCTGCAGTTTCAACTGACCGTCAAT                   GTGGTGGCTGTGATCGTGGCCTTCACAGGTGCCTGCATTACTCAGGACTCTCCTCTCAAAGCCGTG                   CAGATGTTGTGGGTGAACTTCATCATGGACACATTTGCCTCTCTGGCCCTGGCGACGGAGCCACCC                   ACAGAGTCGCTGCTGCTGCGGAAGCCGTACGGCCGCGACAAGCCCCTCATCTCCCGCACCATGATG                   AAGAACATTCTGGGCCACGCCGTGTACCAGCTCGCCATCATCTTCACCCTGCTGTTTGTCGGGGAG                   CTCTTCTTCGACATCGACAGCGGGAGGAATGCGCCCCTGCACTCGCCACCCTCAGAGCACTACACC                   ATCATCTTCAACACGTTCGTCATGATGCAGCTCTTTAACGAGATCAACGCCCGCAAGATCCACGGC                   GAGAGGAACGTGTTCGACGGCATCTTCAGCAACCCCATCTTCTGCACCATCGTTTTGGGCACTTTC                   GGGATTCAGATTGTCATCCTCCAGTTTCGCGGGAAGCCCTTCAGCTGCTCCCCACTATCCACAGAA                   CAGTGGCTCTGGTGCCTGTTTGTTGGTGTTCGGGAGCTGGTCTGGGGACAGGTCATTGCCACCATC                   CCCACCAGCCAGCTCAAGTGCCTGAAGGAAGCCGGGCACGGGCCCGGGAAGGACGAGATGACCGAC                   GAGGAGCTGGCCGAAGGCGAGGAAGAGATCGACCATGCCGAGCGGGAGCTCCGCAGGGGCCAGATC                   CTCTGGTTCCGGGCCCTGAACCCGATTCAGACGCAGATGGAGGTAGTGAGTACCTTCAAGAGAAGC                   GGTTCAGTTCACGGTGCTGTGCGCCGGCGGTCTTCGGTCCTCAGCCAGCTTCATGACGTAACCAAT                   CTTTCTACCCCTACTCACATCCGGGTGGTGAAAGCGTTCCGTACCTCGCTCTATGAAGGCCTGGAG                   AAACCAGAATCCAAGACCTCCATTCACAACTTCATGGCCACGCCCGAGTTTCTGATCAATGACTAC                   ACCCACAACATCCCGCTCATTCACGACACGGACGTGGACGAGAACGAGGAGCGCCTCCGGGCCCCC                   CCGCCCCCGTCCCCCAACCAGAACAACAACGCCATAGACAGCGGCATCTACCTGACCACGCATGTC                   ACCAAGTCAGCTACCTCTTCAGTGTTTTCCTCCAGTCCCGGGAGCCCGCTCCACAGCGTGGAGACG                   TCCCTC TAA   CAAGAACTTGTCTCAG                                           ORF Start: ATG at 61       ORF Stop: TAA at 3835           SEQ ID NO:58   1258 aa   MW at 138346.3 kD                     NOV16a,   MGDMANSSIEFHPKPQQQRDVPQAGGFGCTLAELRTLMELRGAEALQKIEEAYGDVSGLCRRLKTS       CG169088-01       Protein Sequence   PTEGLADNTNDLEKRRQIYGQNFIPPKQPKTFLQLVWEALQDVTLIILEVAAIVSLGLSFYAPPCE                   ESEACGNVSGGAEDEGEAEAGWIEGAAILLSVICVVLVTAFNDWSKEKQFRGLQSRIEQEQKFTVI                   RNGQLLQVPVAALVVGDIAQVKYGDLLPADGVLIQANDLKIDESSLTGESDHVRKSADKDPMLLSG                   THVMEGSGRMVVTAVGVNSQTGIIFTLLGAGGEEEEKKDKKGKQQDGAMESSQTKAKKQDGAVANE                   MQPLKSAEGGEMEEREKKKANAPKKEKSVLQGKLTKLAVQIGKAGLVMSAITVIILVLYFVIETFV                   VEGRTWLAECTPVYVQYFVKFFIIGVTVLVVAVPEGLPLAVTISLAYSVKKMMKDNNLVRHLDACE                   TMGNATAICSDKTGTLTTNRMTVVQSYLGDTHYKEIPAPSALTPKILDLLVHAISINSAYTTKILP                   PEKEGALPRQVGNKTECALLGFVLDLKRDFQPVREQIPEDKLYKVYTFNSVRKSMSTVIRMPDGGF                   RLFSKGASEILLKKCTNILNSNGELRGFRPRDRDDMVRKIIEPMACDGLRTICIAYRDFSAGQEPD                   WDNENEVVGDLTCIAVVGIEDPVRPEVPEAIRKCQRAGITVRMVTGDNINTARAIAAKCGIIQPGE                   DFLCLEGKEFNRRIRNEKGEIEQERLDKVWPKLRVLARSSPTDKHTLVKGIIDSTTGEQRQVVAVT                   GDGTNDGPALKKADVGFAMGIAGTDVAKEASDIILTDDNFTSIVKAVMWGRNVYDSISKFLQFQLT                   VNVVAVIVAFTGACITQDSPLKAVQMLWVNLIMDTEASLALATEPPTESLLLRKPYGRDKPLISRT                   MMKNILGHAVYQLAIIFTLLFVGELFFDIDSGRNAPLHSPPSEHYTIIFNTFVMMQLFUEINARKI                   HGERNVFDGIFSNPIFCTIVLGTFGIQIVIVQFGGKPFSCSPLSTEQWLWCLFVGVGELVWGQVIA                   TIPTSQLKCLKEAGHGPGKDEMTDEELAEGEEEIDHAERELRRCQILWFRGLNRIQTQMEVVSTFK                   RSGSVQGAVRRRSSVLSQLHDVTNLSTPTHIRVVKAFRSSLYEGLEKPESKTSIHNFMATPEFLIM                   DYTHNIPLIDDTDVDENEERLRAPPPPSPNQNNNAIDSGIYLTTHVTKSATSSVFSSSPGSPLHSV                   ETSL                  
 
     [0442] Further analysis of the NOV16a protein yielded the following properties shown in Table 16B.  
               TABLE 16B                       Protein Sequence Properties NOV16a                                        SignalP   No Known Signal Sequence Predicted       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 10; pos. chg 0; neg. chg 2           H-region: length 3; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −5.70           possible cleavage site: between 45 and 46           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 10                                             INTEGRAL   Likelihood =   −6.26   Transmembrane   109-125               INTEGRAL   Likelihood =   −10.14   Transmembrane   157-173           INTEGRAL   Likelihood =   −1.54   Transmembrane   203-219           INTEGRAL   Likelihood =   −12.21   Transmembrane   376-392           INTEGRAL   Likelihood =   −7.96   Transmembrane   413-429           INTEGRAL   Likelihood =   −6.53   Transmembrane   857-873                           900           INTEGRAL   Likelihood =   −5.79   Transmembrane   937-953           INTEGRAL   Likelihood =   −7.64   Transmembrane   1005-1021           INTEGRAL   Likelihood =   −0.69   Transmembrane   1042-1058           PERIPHERAL   Likelihood =   1.27   (at 667)                         ALOM score: −12.21 (number of TMSs: 10)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 116           Charge difference: −2.0 C(−5.0)-N(−3.0)           N &gt;= C: N-terminal side will be inside           &gt;&gt;&gt; membrane topology: type 3a           MITDISC: discrimination of mitochondrial targeting seq                                         R content:   0   Hyd Moment (75):   4.84               Hyd Moment (95):   9.11   G content:   1           D/E content:   2   S/T content:   2                         Score: −6.74           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: PKKEKSV (5) at 353           bipartite: none           content of basic residues: 10.9%           NLS Score: −0.04           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions                                 1073 G   0.84               1074 K   0.85           1075 D   0.85           1076 E   0.89           1077 M   0.89           1078 T   0.89           1079 D   0.89           1080 E   0.89           1081 E   0.89           1082 L   0.89           1083 A   0.89           1084 E   0.89           1085 G   0.89           1086 E   0.89           1087 E   0.89           1088 E   0.89           1089 I   0.89           1090 D   0.89           1091 H   0.89           1092 A   0.89           1093 E   0.89           1094 R   0.89           1095 E   0.89           1096 L   0.89           1097 R   0.89           1098 R   0.89           1099 G   0.89           1100 Q   0.89           1101 I   0.89           1102 L   0.89           1103 W   0.89                         total: 31 residues           Final Results (k = 9/23):           77.8%: endoplasmic reticulum           22.2%: mitochondrial           &gt;&gt; prediction for CG169088-01 is end (k = 9)                  
 
     [0443] 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       Geneseq   Protein/Organism/Length   Match   for the   Expect       Identifier   [Patent #, Date]   Residues   Matched Region   Value               ABG27317   Novel human diagnostic protein    1 . . . 1258   1018/1290 (78%)   0.0           #27308 -  Homo sapiens , 1255 aa.   13 . . . 1255   1108/1290 (84%)           [WO200175067-A2, 11 OCT. 2001]       ABG27322   Novel human diagnostic protein    1 . . . 1258   1008/1259 (80%)   0.0           #27313 -  Homo sapiens , 1210 aa.   13 . . . 1210   1093/1259 (86%)           [WO200175067-A2, 11 OCT. 2001]       ABB58837     Drosophila melanogaster     27 . . . 1063    678/1052 (64%)   0.0           polypeptide SEQ ID NO 3303 -   11 . . . 994     791/1052 (74%)             Drosophila melanogaster , 999 aa.           [WO200171042-A2, 27 SEP. 2001]       ABP41721   Human ovarian antigen HSYEC21,   572 . . . 1258     532/689 (77%)   0.0           SEQ ID NO: 2853 -  Homo sapiens ,   8 . . . 654    592/689 (85%)           654 aa. [WO200200677-A1,           03 JAN. 2002]       AAG49832     Arabidopsis thaliana  protein   25 . . . 1046    391/1034 (37%)   e-166           fragment SEQ ID NO: 63081 -   106 . . . 1030     564/1034 (53%)             Arabidopsis thaliana , 1066 aa.           [EP1033405-A2, 06 SEP. 2000]                  
 
     [0444] In a BLAST search of public sequence databases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16D.  
               TABLE 16D                          Public BLASTP Results for NOV16a                                         NOV16a   Identities/           Protein       Residues/   Similarities       Accession       Match   for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value                                         Q64568   Plasma membrane calcium-   1 . . . 1258   1236/1258 (98%)   0.0           transporting ATPase 3 (EC   1 . . . 1258   1245/1258 (98%)           3.6.3.8) (PMCA3) (Plasma           membrane calcium pump           isoform 3) (Plasma           membrane calcium ATPase           isoform 3) -  Rattus               norvegicus  (Rat), 1258 aa.       Q16720   Plasma membrane calcium-   1 . . . 1258   1216/1258 (96%)   0.0           transporting ATPase 3 (EC   1 . . . 1220   1218/1258 (96%)           3.6.3.8) (PMCA3) (Plasma           membrane calcium pump           isoform 3) (Plasma           membrane calcium ATPase           isoform 3) -  Homo sapiens             (Human), 1220 aa.       A34308   Ca2 + transporting ATPase   1 . . . 1158   1124/1158 (97%)   0.0           (EC 3.6.1.38), plasma   1 . . . 1144   1133/1158 (97%)           membrane isoform 3a - rat,           1159 aa.       P11505   Plasma membrane calcium-   1 . . . 1258   1015/1265 (80%)   0.0           transporting ATPase 1 (EC   1 . . . 1258   1129/1265 (89%)           3.6.3.8) (PMCA1) (Plasma           membrane calcium pump           isoform 1) (Plasma           membrane calcium ATPase           isoform 1) -  Rattus               norvegicus  (Rat), 1258 aa.       P20020   Plasma membrane calcium-   1 . . . 1258   1009/1265 (79%)   0.0           transporting ATPase 1 (EC   1 . . . 1258   1128/1265 (88%)           3.6.3.8) (PMCA1) (Plasma           membrane calcium pump           isoform 1) (Plasma           membrane calcium ATPase           isoform 1) -  Homo sapiens             (Human), 1258 aa.                  
 
     [0445] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16E.  
               TABLE 16E                          Domain Analysis of NOV16a                                     Identities/                   Similarities           NOV16a Match   for the   Expect       Pfam Domain   Region   Matched Region   Value               Cation_ATPase_N    44 . . . 123   22/89 (25%)   0.0001               57/89 (64%)       E1-E2_ATPase   196 . . . 284   41/99 (41%)   2.4e−29               74/99 (75%)       E1-E2_ATPase   355 . . . 463   37/110 (34%)    9.8e−19               81/110 (74%)        Hydrolase   467 . . . 815   45/366 (12%)    1.6e−12               234/366 (64%)        Cation_ATPase_C    911 . . . 1067   40/204 (20%)    3.5e−20               124/204 (61%)                   
 
     Example 17.  
     [0446] The NOV17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A.  
               TABLE 17K                       NOV17 Sequence Analysis                                                SEQ ID NO:59   4092 bp                     NOV17a,     GGGCGGTGGTGCCGCGTCGGGGAAGAGCGCATCCCGCGGGGTCCCGAGCCCGGCGCTGGCGGAGAG         CG169201-01       DNA Sequence     ACGGGGGCGCCCCCTCCCCACAGGAGGAGCCTCGCGCTCCTCCGCCATCCTTCCCCCGCGCGGCGG                       GCTCGCCTTCTCAGTGGGTGCTGCGCGAGCTGCCGGCCCGGGGTGCCGGGGCCAGATAAGGGCGAT                       CCGCGGGGCCGCCGCCCCCGGGTCAGGCAGGCCGGGGGCGGGCCGCGAGTGAGGCGGCGCCGCCGC                       TAGGCTGCGGGCGGCTGGGGGCCGGGGGAGCGCGGAGAGCCGAGGGGGGCAGGCGGCGAGCGGGTG                       GCCCGGCCGCCCGCCTCGCTGCTCCGCTTGGCGCCGCCGGCCCACGCCGCAGTGTGTTTTGTGGAC                       GGCGCCTTCCCAGACAGCCCGGTAGAGCCCAGCTCAGCGCCCGGCAGCCTTCGACGCG   ATG TTCCG                   CCGGAGCTTGAATCGTTTTTGTGCTGGAGAAGAGAAACGAGTTGGCACACGCACAGTGTTTGTTGG                   CAATCATCCAGTTTCGGAAACAGAAGCTTACATTGCACAAAGATTTTGTGATAATAGAATAGTCTC                   ATCTAAGTATACACTTTGGIAATTTTCTCCCAAAGAATCTGTTTGAACAGTTTAGAAGAATTGCAAA                   TTTTTATTTTCTCATAATCTTCCTTGTACAGGTCACAGTAGACACACCAACTAGCCCAGTTACCAG                   TGGACTTCCACTTTTCTTTGTTATAACTGTTACAGCCATCAAGCAGGGATATGAGGATTGGCTGAG                   ACACAGAGCTGACAATGAAGTCAACAAAACCACTGTTTACATTATTGAAAATGCAAAGCGAGTGAG                   AAAAGAAAGTGAAAAAATCAAGGTTGGTGATGTAGTAGAAGTACAGGCAGATGAAACCTTTCCCTG                   TGATCTTATTCTTCTATCATCTTGCACCACTGATGGAACCTGTTATGTCACTACAGCCAGTCTTGA                   TGGGGAATCCAATTGCAAGACACATTATGCAGTACGTGATACCATTGCACTGTGTACAGCAGAATC                   CATCGATACCCTCCGAGCAGCAATTGAATGTGAACAGCCTCAACCTCACCTCTACAAATTTGTTGG                   GCGAATCAATATCTACAGTAATAGTCTTGAGGCTGTTGCCAGGTCTTTGGGACCTGAAAATCTCTT                   GCTGAAAGGAGCTACGCTAAAAAATACCGAGAAGATATATGGAGTTGCTGTTTACACTGGAATGGA                   AACCAAAATGGCTTTGAACTACCAAGGGAAATCTCAGAAACGTTCTGCTGTTGAAAAATCTATTAA                   TGCTTTCCTGATTGTATATTTATTTATCTTACTGACCAAAGCTGCAGTATGCACTACTCTAAAGTA                   TGTTTGGCAAAGTACCCCATACAATGATGAACCTTGGTATAACCAAAAGACTCAGAAAGAGCGAGA                   GACCTTGAAGGTTTTAAAAATGTTCACCGACTTCCTATCATTTATGGTTCTATTCAACTTTATCAT                   TCCTGTCTCCATGTACGTCACAGTAGAAATGCAGAAATTCTTGGGCTCCTTCTTCATCTCATGGGA                   TAAGGACTTTTATGATGAACAAATTAATGAAGGAGCCCTGGTTAACACATCAGACCTTAATGAAGA                   ACTTGGTCAGGTGGATTATGTATTTACACATAAGACTGGAACACTCACTGAAAACAGCATCGAATT                   CATTGAATGCTGCATAGATGGCCACAAATATAAAGGTGTAACTCAAGAGGTTGATGGATTATCTCA                   AACTGATCGAACTTTAACATATTTTGACAAAGTAGATAAGAATCGAGAAGAGCTGTTTCTACGTGC                   CTTGTGTTTATGTCATACTGTAGAAATCAAAACAAACGATGCTGTTGATGGAGCTACAGAATCAGC                   TGAATTAACCTATATCTCCTCTTCACCAGATGAAATAGCTTTGGTGAAAGGAGCTAAAAGGTACGG                   GTTCACATTTTTAGGAAATCGAAATGGATATATGAGAGTAGAGAGCCAAAGAAAAGAAATAGAAGA                   ATATGAACTTCTTCAAACCTTAACTTTGATGCTGTCCGGCGACAGTATGAGTGTAATTGTGAAGAC                   TCAAGAAGGAGACATACTTCTCTTTTGTAAAGGAGCAGACTCCGCAGTTTTTCCCAGAGTGCAAAA                   TCATGAAATTGAGTTAACTAAAGTCCATGTGGAACGTAATGCAATGGATGGGTATCGGACACTCTG                   TGTAGCCTTCAAAGAAATTGCTCCAGATGATTATGAAAGAATTAACAGACAGCTCATAGAGGCAAA                   AATGGCCTTACAAGACAGAGAAGAAAAATCGAAAAAGTTTTCGATGATATTGAGACAAAACATGAA                   TTTAATTGGAGCCACTGCAGTTGAAGACAAGCTACAAGATCAAGCTGCAGAGACCATTGAAGCTCT                   GCATGCAGCAGGCCTGAAAAGTCTGGGTGCTCACTGGGGACAAGATGGAGACAGCTAATCCACATG                   CTATGCCTGCCGCCTTTTCCAGACCAACACTGAGCTCTTAGAACTAACCACAAAAACCATTGAAGA                   AAGTGAAAGGAAAGAAGATCGATTACATGAATTATTGATAGAATATCGCAAGAAATTGCTGAATGA                   GTTTCCTAAAAGTACTAGAAGCTTTAAAAAGCATGGACAGAACATCAGGAATATGGAATTAATAAT                   AGATGGCTCCACATTGTCACTCATACTAAATTCTAGTCAAGACTCTAGTTCACAATTACAAAAAAG                   CATTTTCCTACAAATATGTATGAAGTGTACTGCAGTGCTCTGCTGTCGGATGGCACCATTACAGAA                   AGCCCAGATTGTCAGAATGGTGAAGAATTTAAAAGGCAGCCCAATAACTCTGTCGATAGGTGATGG                   TGCCAATGATGTTAGTATGATCTTGGAATCCCATGTGGAATAAAGGTATTAAAGGCAAGAAAATCG                   CCAAGCAGCTAGATAGCGGAAAATTATTCTGTTCCAAAGTTTAAACACTTAAGAACTGCTGTTAAC                   TCATGGACATCTATATTATGTGAGAATAGCACACCTTGTAAAGTACTTCTTCTATAAGAACCTTTG                   TTTCATTTTGCCACAGTTTTTGTACCAGTTCTTCTGTGGATTCTCACAACAGCCACTGTATGATGC                   TGCTTACCTTACAATGTACAATATCTGCTTCACATCCTTGCCCATCCTGGCCTATAGTCTACTAAA                   ACAGCACATCAACATTGACACTCTGACCTCAGATCCCCGATTGTATATGAAAATTTCTGGCAATGC                   CATGCTACACTTGGGCCCCTTCTTATATTGGACATTTCTGGCTGCCTTTGAAGAAACAGTGTTCTT                   CTTTGGGACTTACTTTCTTTTTCAGAACTGCATCCCTAGAAGAAAATGGAAAGGTATACAAAACTG                   GACTTTTGGAACCATTGTTTTTACAGTCTTAAGTATTCACTGTAACCCTGAACTTGCCTTGGATAC                   CCGATTCTGGACGTGGATAAATCACTTTGTGATTTGGGGTTCTTTAGCCTTCTATGTATTTTTCTC                   ATTCTTCTGCGGAGGAATTATTTGGCCTTTTCTCAAGCAACAGAGAATGTATTTTGTATTTGCCCA                   AATGCTGTCTTCTGTATCCACATGGTTGGCTATAATTCTTCTAATATTTATCAGCCTGTTCCCTGA                   GATTCTTCTGATAGTATTAAAGAATGTAAGAAGAAGAAGTGCCAAAGTAAGAACTAGTCTGAGCTG                   TAGAAGGGCATCTGACTCATTATCCGCCAGACCTTCAGTCAGACCTCTTCTTTTACGAACATTCTC                   AGACGAATCTAATGTATTGTAACAGAATCCGAATCTTGAACTGCCTATGTTATTGTCCTACAAGCA                   TACTGACAGTGGTTACAGCTAAAAAAGAAAGCATGAAGAAACAAACTAAAAAAGTTATCATCTCAG                   GATACTTGATACGCAACACACTAAACCACTCTCATGTCTAGAGTTCACAATAAATGTTCATTAAAA                   TACCAAATGATTCTCTTAAGCATTTACCATTATTGTAAGTAGCCTTTATGGCCAAAGCTGTAAGTT                                         ORF Start: ATG at 455       ORF Stop: TAA at 3848           SEQ ID NO:60   1131 aa   MW at 129671.9 kD                     NOV 17a,   MFRRSLNRFCAGEEKRVGTRTVFVGNHPVSETEAYIAQRFCDNRIVSSKYTLWNFLPKNLFEQFRR       CG169201-01       Protein Sequence   IANFYFLIIFLVQVTVDTPTSPVTSGLPLFFVITVTAIKQGYEDWLRHRADNEVNKSTVYIIENAK                   RVRKESEKIKVGDVVEVQADETFPCDLILLSSCTTDGTCYVTTASLDGESNCKTHYAVRDTIALCT                   AESIDTLRAAIECEQPQPDLYKFVGRINIYSNSLEAVARSLGPENLLLKGATLAATEKIYGVAVYT                   GMETKMALNYQGKSQKRSAVEKSINAFLIVYLFILLTKAAVCTTLKYVWQSTPYNDEPWAAQKTQK                   ERETLKVLKMFTDFLSFMVLFNFIIPVSMYVTVEMQKFLGSFFISWDKDFYDEEINEGALVNTSDL                   NEELGQVDYVFTDKTGTLTENSMEFIECCIDGHKYKGVTQEVDGLSQTDGTLTYFDKVDKNREELF                   LRALCLCHTVEIKTNDAVDGATESAELTYISSSPDEIALVKGAKRYGFTFLGNRNGYMRVENQRKE                   IEEYELLHTLNFDAVRRRMSVIVKTQEGDILLPCKGADSAVFPRVQNHEIELTKVHVERNAMDGYR                   TLCVAFKEIAPDDYERINRQLIEAKMALQDREEKMEKVFDDIETNMNLIGATAVEDKLQDQAAETI                   EALHAAGLKVWVLTGDKMETAKSTCYACRLFQTNTELLELTTKTIEESERKEDRLHELLIEYRKKL                   LHEFPKSTRSFKKAWTEHQEYGLIIDCSTLSLILNSSQDSSSNNYKSIFLQICMKCTAVLCCRMAP                   LQKAQIVRMVKNLKGSPITLSIGDGANDVSMILESHVGIGIKGKEGRQAARNSDYSVPKFKHLKKL                   LLAHGHLYYVRIAHLVQYFFYKNLCFILPQFLYQFFCGFSQQPLYDAAYLTMYNICFTSLPILAYS                   LLEQHINIDTLTSDPRLYMKISGNAMLQLGPFLYWTFLAAFEGTVFFFGTYFLFQTASLEEMGKVY                   GNAATFGTIVFTVLVFTVTLKLALDTRFWTWINHVIWGSLAFYVFFSFAAAAIIWPFLKQQRMYFV                   EAQMLSSVSTWLAIILLIFISLFPEILLIVLKNVRRRSARVRTSLSCRRASDSLSARPSVRPLLLR                   TFSDESNVL                  
 
     [0447] Further analysis of the NOV17a protein yielded the following properties shown in Table 17B.  
               TABLE 17B                       Protein Sequence Properties NOV17a                                        SignalP   No Known Signal Sequence Predicted       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 8; pos. chg 3; neg. chg 0           H-region: length 4; peak value −15.26           PSG score: −19.66           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −10.47           possible cleavage site: between 32 and 33           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 8                                             INTEGRAL   Likelihood =   −2.39   Transmembrane   67-83               INTEGRAL   Likelihood =   −1.70   Transmembrane    88-104           INTEGRAL   Likelihood =   −7.06   Transmembrane   290-306           INTEGRAL   Likelihood =   −3.72   Transmembrane   347-363           INTEGRAL   Likelihood =   0.16   Transmembrane   774-790           INTEGRAL   Likelihood =   −5.47   Transmembrane    997-1013           INTEGRAL   Likelihood =   −1.75   Transmembrane   1024-1040           INTEGRAL   Likelihood =   −12.21   Transmembrane   1070-1086           PERIPHERAL   Likelihood =   0.90   (at 961)                         ALOM score: −12.21 (number of TMSs: 8)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 74           Charge difference: −3.0 C(−1.0)-N( 2.0)           N &gt;= C: N-terminal side will be inside           &gt;&gt;&gt; membrane topology: type 3a           MITDISC: discrimination of mitochondrial targeting seq                                         R content:   3   Hyd Moment (75):   20.21               Hyd Moment (95):   17.79   G content:   1           D/E content:   2   S/T content:   1                         Score: −1.16           Gavel: prediction of cleavage sites for mitochondrial preseq           R-2 motif at 18 NRF|CA           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: RKEDRLHELLIEYRKKL at 710           bipartite: RKKLLHEFPKSTRSFKK at 723           content of basic residues: 11.2%           NLS Score: 0.51           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           XXRR-like motif in the N-terminus: FRRS           none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: found           KLLLAHGHL at 857           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions                                 605 D   0.83               606 D   0.83           607 Y   0.83           608 E   0.85           609 R   0.85           610 I   0.85           611 N   0.86           612 R   0.95           613 Q   0.96           614 L   0.96           615 I   0.96           616 E   0.96           617 A   0.96           618 K   0.96           619 M   0.96           620 A   0.96           621 L   0.96           622 Q   0.96           623 D   0.96           624 R   0.96           625 E   0.96           626 E   0.96           627 K   0.96           628 M   0.96           629 E   0.96           630 K   0.96           631 V   0.96           632 F   0.96           633 D   0.96           634 D   0.96           635 I   0.96           636 E   0.96           637 T   0.96           638 N   0.96           639 M   0.96           640 N   0.96           641 L   0.83           642 I   0.53           697 L   0.72           698 E   0.72           699 L   0.72           700 T   0.72           701 T   0.72           702 K   0.72           703 T   0.72           704 I   0.72           705 E   0.72           706 E   0.72           707 S   0.72           708 E   0.72           709 R   0.72           710 K   0.72           711 E   0.72           712 D   0.72           713 R   0.72           714 L   0.72           715 H   0.72           716 E   0.72           717 L   0.72           718 L   0.72           719 I   0.72           720 E   0.72           721 Y   0.72           722 R   0.72           723 K   0.72           724 K   0.72           725 L   0.72                         total: 67 residues           Final Results (k = 9/23):           55.6%: endoplasmic reticulum           11.1%: mitochondrial           11.1%: vacuolar           11.1%: vesicles of secretory system           11.1%: Golgi           &gt;&gt; prediction for CG169201-01 is end (k = 9)                  
 
     [0448] 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       Geneseq   Protein/Organism/Length   Match   for the   Expect       Identifier   [Patent #, Date]   Residues   Matched Region   Value                                         ABP52158   Human 67076 transporter protein   1 . . . 1131   1127/1131 (99%)    0.0           SEQ ID NO: 14 -  Homo sapiens ,   1 . . . 1129   1128/1131 (99%)            1129 aa. [WO200255701-A2,           18 JUL. 2002]       ABG61547   Human transporter and ion channel,   1 . . . 1131   1126/1131 (99%)    0.0           TRICH17, Incyte ID 7477243CD1 -   1 . . . 1129   1127/1131 (99%)              Homo sapiens , 1129 aa.           [WO200240541-A2, 23 MAY 2002]       AAO14200   Human transporter and ion channel   1 . . . 1087   720/1100 (65%)   0.0           TRICH-17 -  Homo sapiens , 1192 aa.   5 . . . 1096   874/1100 (79%)           [WO200204520-A2, 17 JAN. 2002]       AAE24584   Human phospholipid transporter,   1 . . . 1109   725/1124 (64%)   0.0           67118 protein #2 -  Homo sapiens ,   6 . . . 1121   882/1124 (77%)           1135 aa. [WO200240674-A2,           23 MAY 2002]       AAE24583   Human phospholipid transporter,   1 . . . 1109   725/1124 (64%)   0.0           67118 #1 -  Homo sapiens , 1134 aa.   5 . . . 1120   882/1124 (77%)           [WO200240674-A2, 23 MAY 2002]                  
 
     [0449] In a BLAST search of public sequence databases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17D.  
               TABLE 17D                          Public BLASTP Results for NOV17a                                         NOV17a               Protein       Residues/   Identities/       Accession       Match   Similarities for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value                                         CAD44426   Sequence 13 from Patent   1 . . . 1131   1127/1131 (99%)    0.0           WO02055701 -  Homo sapiens     1 . . . 1129   1128/1131 (99%)            (Human), 1129 aa.       Q8WX24   BB206I21.1 (ATPase, class VI,   10 . . . 988    961/979 (98%)   0.0           type 11C) -  Homo sapiens  (Human),   1 . . . 962    961/979 (98%)           962 aa (fragment).       P98197   Potential phospholipid-transporting   1 . . . 1087   711/1103 (64%)    0.0           ATPase IH (EC 3.6.3.1) -  Mus     5 . . . 1099   869/1103 (78%)              musculus  (Mouse), 1187 aa.       CAD44430   Sequence 19 from Patent   19 . . . 1083    611/1105 (55%)    0.0           WO02055701 -  Homo sapiens     19 . . . 1089    788/1105 (71%)            (Human), 1177 aa.       P98196   Potential phospholipid-transporting   338 . . . 1109    486/786 (61%)   0.0           ATPase IS (EC 3.6.3.1) -  Homo     6 . . . 783    602/786 (75%)             sapiens  (Human), 797 aa           (fragment).                  
 
     [0450] 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   Expect           Domain   Region   Matched Region   Value                       Hydrolase   403 . . . 837   42/449 (9%)   0.019                   262/449 (58%)                      
 
     Example 18.  
     [0451] 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:61   1992 bp                     NOV18a,     CTCTCTTTTGTTTCTCTTGC   ATG CAAGGCCCCATACTGTGGATCATGGCAAATCTGAGCCAGCCCT       CG50303-01       DNA Sequence   CCGAATTTGTCCTCTTGGGCTTCTCCTCCTTTGGTGAGCTGCAGGCCCTTCTGTATGGCCCCTTCC                   TCATGCTTTATCTTCTCGCCTTCATGGGAAACACCATCATCATAGTTATGGTCATAGCTGACACCC                   ACCTACATACACCCATGTACTTCTTCCTGGGCAATTTTTCCCTGCTGGAGATCTTAATAACCATGA                   CTGCAGTGCCCAGGATGCTCTCAGACCTGCTGGTCCCCCACAAAGTCATTACCTTCACTAACTGCA                   TGGTCCACTTCTACTTCCACTTTTCCCTGGGGTCCACCTCCTTCCTCATCCTGACAGACATGGCCC                   TTGATCGCTTTGTGGCCATCTGCCACCCACTGCGCTATGGCACTCTGATGAGCCAAGCTATGTGTG                   TCCAGCTGGCTGGGGCTGCCTGGGCAGCTCCTTTCCTAGCCATGGTACCCACTGTCCTCTCCCGAG                   TCCTATCTTGATTACTGCCATGCGACGTCATCAACCACTTCTTCTGTGACAATGAACCTCTCCTGC                   AGTTGTCATGCTCTGACACTCGCCTGTTCGAATTCTGGGACTTTCTGATGGCCTTGACCTTTGTCC                   TCAGCTCCTTCCTGGTGACCCTCATCTCCTATGGCTACATAGTGACCACTGTGCTGCAAATCCCCT                   CTGCCAGCAGCTGCCAGAAGGCTTTCTCCACTTGCGGGTCTCACCTCACACTAATCTTAATCAACT                   ACAGTAGTACCATCTTTCTGTATGTCAGGCCTGGCAAAGCTCACTCTGTGCAAGTAAGGAAGGTCG                   TGGCCTTGGTGACTTCAGTTCTCACCCCCTTTCTCAATCCCTTTATCCTTACCTTCTGCAATCAGA                   CAGTTAAAACAGTGCTACAGGGGCAGATG TAG   AGGCTGAAAGGCCTTTGCAAAACACAATGATGAG                       CC                                           ORF Start: ATG at 21       ORF Stop: TAG at 954           SEQ ID NO:62   311 aa   MW at 34714.8 kD                     NOV18a,   MGGPTLWIMANLSQPSEFVLLGFSSFGELQALLYGPFLMLYLLAFMGNTIIIVMVIADTHLHTPMY       CG50303-01       Protein Sequence   FFLGNFSLLEILVTMTAVPRMLSDLLVPHKVITFTGCMVQFYFHFSLGSTSFLILTDMALDRFVAI                   CHPLRYGTLMSRANCVQLAGAAWAAPFLAMVPTVLSRAHLDYCHGDVIAAFFCDNEPLLQLSCSDT                   RLLEFWDFLMALTFVLSSFLVTLISYGYIVTTVLRIPSASSCQKAFSTCGSHLTLVFIGYSSTIFL                   YVPPGKAHSVOVRKVVALVTSVLTPFLNPFILTFCNQTVKTVLQCQM                                     SEQ ID NO:63   964 bp                     NOV18b,     GGCCCCATACTGTGGATC   ATG GCAAATCTGAGCCAGCCCTCCGAATTTGTCCTCTTGGGCTTCTCC       CG50303-03       DNA Sequence   TCCTTTGGTGAGCTGCAGGCCCTTCTGTATGGCCCCTTCCTCATGCTTTATCTTCTCGCCTTCATG                   GGAAACACCATCATCATAGTTATGGTCATAGCTGACACCCACCTACATACACCCATGTACTTCTTC                   CTGGGCAATTTTTCCCTGCTGGAGATCTTGGTAACCATGACTGCAGTGCCCAAAATCCTCTCAGAC                   CTGTTGGTCCCCCACAAAGTCATTACCTTCACTGGCTGCATGGTCCAGTTCTACTTCCACTTTTCC                   CTGGGGTCCACCTCCTTCCTCATCCTGACAGACATGGCCCTTGATCGCTTTGTGGCCATCTGCCAC                   CCACTGCGCTATGGCACTCTGATGAGCCGGCTATGTGTGTCCAGCTGGCTGGAAGCTGCCTAAGCA                   GCTCCTTTCCTAGCCATGGTACCCACTGTCCTCTCCCGACCTCATCTTGATTACTGCCATGGCGAC                   GTCATCAACCACTTCTTCTGTGACAATGAACCTCTCCTGCAGTTGTCATGCTCTGACACTCGCCTG                   TTGGAATTCTGGGACTTTCTGATGGCCTTGACCTTTGTCCTCAGCTCCTTCCTGGTGACCCTCATC                   TCCTATGGCCTACATAGTGACCACTGTGCTGCGGATCCCCTCTGCCAGCAGCTGCCAGAAACTTTC                   TCCACTTGCGGGTCTCACCTCACACTGGTCTTCATCGGCTACAGTAGTACCATCTTTCTGTATGTC                   AGGCCTGGCAAAGCTCACTCTGTGCAAGTCAGGAAGGTCGTGGCCTTGGTGACTTCAGTTCTCACC                   ACGCCTGGCAAAGCTCACTCTGTGCAAGTCAGGAAGGTCGTGGCCTTGGTGACTTCAGTTCTCACC                   CCCTTTCTCAATCCCTTTATCCTTACCTTCTGCAATCAGACAGTTAAAACAGTGCTACAGAAGCAG                                         ORF Start: ATG at 19       ORF Stop:TGA at 958           SEQ ID NO:64   313 aa   MW at 34902.0 kD                     NOV18b,   TMANLSQPSEFVLLGFSSFGELQALLYGPFLMLYLLAFMGNTIIIVMVIADTHLHTPMYFFLGNFSL       CG50303-03       Protein Sequence   LEILETLVTMTAVPRMLSDLLVPHKVITFTGCMVQFYFHFSLGSTSFLILTDLDRAAAICHPLRYGT                   LMSRAMCVQLAGAAWAAPFLAMVPTVLSRAHLDYCHGDVINHFFCDNEPLLQLSCSDTRLLEEFWDF                   LMALTFVLSSFLVTLISYGYIVTTVLRIPSASSCQKAFSTCGSHLTLVFIGYSSTIFLYVRPGKAH                   SVQVRKVVALVTSVLTPFLNPFILTFCNQTVKTVLGGQMQRLICGLCKAQ                                     SEQ ID NO:65   964 bp                     NOV18c,     C   ACC AAGCTTCCCACCATGGCAAATCTGAGCCAGCCCTCCGAATTTGTCCTCTTGGGCTTCTCCTC       276863879 DNA       Sequence   CTTTGGTGAGCTGCAGGCCCTTCTGTATGGCCCCTTCCTCATGCTTTATCTTCTCGCCTTCATGGG                   AAACACCATCATCATAGTTATGGTCATAGCTGACACCCACCTACATACACCCATGTACTTCTTCCT                   GGGCAATTTTTCCCTGCTGGAGATCTTGGTAACCATGACTGCAGTGCCCAAAATGCTCTCAGACCT                   GTTGGTCCCCCACAAAGTCATTACCTTCACTGGCTGCATGGTCCAGTTCTACTTCCACTTTTCCCT                   GGGGTCCACCTCCTTCCTCATCCTGACAGACATGGCCCTTGATCGCTTTGTGGCCATCTGCCACCC                   ACTCCGCTATGGCACTCTGATGAGCCGGGCTATGTGTGTCCAGCTAACTGGGGCTGCCTCAACAGC                   TCCTTTCCTAGCCATGGTACCCACTGTCCTCTCCCGAGCTCATCTTGATTACTGCCATGGCGACGT                   CATCAACCACTTCTTCTGTGACAATGAACCTCTCCTGCAGTTCTCATGCTCTGACACTCCCCTGTT                   GGAATTCTGGGACTTTCTGATGGCCTTGACCTTTGTCCTCAGCTCCTTCCTGGTGACCCTCATCTC                   CTATGGCTACATAGTGACCACTGTGCTGCGGATCCCCTCTGCCAGCAGCTGCCAGAAGGCTTTCTC                   CACTTGCGGGTCTCACCTCACACTGGTCTTCATCGGCTACAGTAGTACCATCTTTCTGTATGTCAG                   GCCTGGCAAAGCTCACTCTGTGCAAGTCAGGAAGGTCGTGGCCTTAATGACTTCAGTTCTCACCCC                   CTTTCTCAATCCCTTTATCCTTACCTTCTGCAATCAGACAGTTAAAACAGTGCTACAGGAAAAGAT                   GCAGAGGCTGAAAGGCCTTTGCAAGGCACAACTCGAGCAAC                                         ORF Start: at 2       ORF Stop: end of sequence           SEQ ID NO:66   321 aa   MW at 35742.0 kD                     NOV18c,   TKLPTMANLSQPSEFVLLGFSSFGELQALLYGPFLMLYLLAFMGNTIIIVMVTADTHLHTPMYFFL       276863879       Protein Sequence   GNFSLLEILVTMTAVPRMLSDLLVPHKVITFTGCMVQFYFHFSLGSTSFLILTDMALDRFVAICHP                   ILRYGTLMSRMCVQLAGAAWAAPFLAMVPTVLSRAHLDYCHGDVIAAFFCDNEPLLQLSCSDTRLL                   EFWDFLMALTFVLSSFLVTLISYGYIVTTVLRIPSASSCQKAFSTCGSHLTLVFIGYSSTIFLYVR                   PGKAHSVQVRKVVALVTSVLTPFLNPFILTFCNQTVKTVLGGQMQRLKGLCKAQLEG                                     SEQ ID NO:67   769 bp                     NOV18d,     C   ACC AAGCTTGGAAACACCATCATCATAGTTATCGTCATAGCTGACACCCACCTAAATACACCCATG       276863902       DNA Sequence   TACTTCTTCCTGGGCAATTTTTCCCTGCTGGAGATCTTGGTAACCATGACTGCAGTGCCCAGGATGC                   TCTCAGACCTGTTGGTCCCCCACAAAGTCATTACCTTCACTGGCTGCATAATCCAGTTCTACTTCCA                   CTTTTCCCTGGGGTCCACCTCCTTCCTCATCCTGACAGACATGGCCCTTGATCGCTTTGTAACCATC                   TGCCACCCACTGCGCTATGGCACTCTGATGAGCCGGGCTATGTGTGTCCAGCTGGCTAAGGCTGCCT                   GGGCAGCTCCTTTCCTAGCCATGGTACCCACTGTCCTCTCCCGAGCTCATCTTGATTACTGCCATAA                   CGACGTCATCAACCACTTCTTCTGTGACAATGAACCTCTCCTGCAGTTGTCATGCTCTGACACTCGC                   CTGTTGGAATTCTGGGACTTTCTGATGGCCTTGACCTTTGTCCTCAGCTCCTTCCTAATGACCCTCA                   TCTCCTATGGCTACATAGTGACCACTGTGCTGCGGATCCCCTCTGCCAGCAGCTGCCAGAAGGCTTT                   CTCCACTTGCGGGTCTCACCTCACACTGGTCTTCATCGGCTACAGTAGTACCATCTTTCTGTATGTC                   AGGCCTGGCAAAGCTCACTCTGTGCAAGTCAGGAAGGTCGTGGCCTTGGTGACTTCAGTTCTAACCC                   CCTTTCTCAATCCCTTTATCCTTCTCGAGGGC                                         ORF Start: at 2       ORF Stop: end of sequence           SEQ ID NO:68   256 aa   MW at 28495.4 kD                     NOV18d,   THLGNTIIIVMVIADTHLHTPMYFFLGNFSLLEILVTMTAVPRMLSDLLVPHKVITFTGCMVQFYF       27686390       Protein Sequence   HFSLGSTSFLILTDMALDRFVAICHPLRYGTLMSRAMCVQLAGAAWAAPFLAMVPAALSRAHLDYC                   HGDVINHFFCDWEPLLQLSCSDTRLLEFWDFLMALTFVLSSFLVTLISYGYIVTAALRIPSASSCQ                   KAFSTCGSHLTLVFIGYSSTIFLYVRPGKAHSVQVRKVVALVTSVLTPFLNPFILLEG                                     SEQ ID NO:69   992 bp                     NOV18e,     CTGTCTTTTGTTTCTCTTGC   ATG CAAGGCCCCATACTGTGGATCATGGCAAATCTGAGCCAGCCCT       CG50303-01       DNA Sequence   CCGAATTTGTCCTCTTGGGCTTCTCCTCCTTTGGTGAGCTGCAAACCCTTCTGTATGGCCCCTTCC                   TCATGCTTTATCTTCTCGCCTTCATGGGAAACACCATCATCATAGTTATGGTCATAGCTGACACCC                   ACCTACATACACCCATGTACTTCTTCCTGGGCAATTTTTCCCTGCTGGAGATCTTAATAACCATGA                   CTGCAGTGCCCAGGATGCTCTCAGACCTGCTGGTCCCCCACAAAGTCATTACCTTCACTGGCTGCA                   TGGTCCAGTTCTACTTCCACTTTTCCCTGCGGTCCACCTCCTTCCTCATCCTGACAGACATAACCC                   TTGATCGCTTTGTGGCCATCTGCCACCCACTGCGCTATGGCACTCTGATGAGCCGGGCTATGTGTG                   TCCAGCTGGCTGGGGCTGCCTGGCCAGCTCCTTTCCTAGCCATGGTACCCACTGTCCTCTCCCGAG                   CTCATCTTGATTACTGCCATGGCGACGTCATCAACCACTTCTTCTGTGACAATGAACCTCTCCTGC                   AGTTGTCATGCTCTGACACTCCCCTGTTGGAATTCTGGGACTTTCTGATGGCCTTCACCTTTGTCC                   TCAGCTCCTTCCTGGTGACCCTCATCTCCTATGGCTACATAGTGACCACTGTGCTGCGGATCCCCT                   CTGCCAGCAGCTGCCAGAAGGCTTTCTCCACTTGCGGGTCTCACCTCACACTAATCTTCATCAACT                   ACAGTAGTACCATCTTTCTGTATGTCAGGCCTGGCAAAGCTCACTCTGTGCAAGTCAGGAAGGTCG                   TGGCCTTGGTGACTTCAGTTCTCACCCCCTTTCTCAATCCCTTTATCCTTACCTTCTGCAATCAGA                   CAGTTAAAACAGTGCTACAGGGGCAGATG TAG   AGGCTGAAAGGCCTTTGCAAGGCACAATGATGAG                     CC                                         ORF Start: ATG at 21       ORF Stop: TAG at 954           SEQ ID NO:70   311 aa   MW at 34714.8 kD                     NOV18e,   MQGPILWIMANLSQPSEFVLLGFSSFGELQALLYGPFLMLYLLAFMGNTIIIVMVIADTHLHTPMY       CG50303-01       Protein Sequence   FFLGNFSLLEILVTMTAVPRMLSDLLVPHKVITFTGCMVQFYFHFSLGSTSFLILTDMALDRFVAI                   CHPLRYGTLMSRAMCVQLAGAAWAAPFLAMVPTVLSRAHLDYCHGDVINHFFCDNEPLLQLSCSDT                   RLLEFWDFLMALTFVLSSFLVTLISYGYIVTTVLRIPSASSCQKAFSTCGSHLTLVFIGYSSTIFL                   YVRPGKAHSVQVRKVVALVTSVLTPFLNPFILTFCNQTVKTVLQGQM                                     SEQ ID NO:71   992 bp                     NOV18f,     CTGTCTTTTGTTTCTCTTGC   ATG CAAGGCCCCATACTGTGGATCATGGCAATCTGAGCCAGCCCT       CG50303-02       DNA Sequence   CCGAATTTGTCCTCTTGGGCTTCTCCTCCTTTCGTGACCTGCAGGCCCTTCTGTATAACCCCTTCC                   TCATGCTTTATCTTCTCGCCTTCATGGGAAACACCATCATCATAGTTATGGTCATAGCTGACACCC                   ACCTACATACACCCATGTACTTCTTCCTGGGCAATTTTTCCCTGCTGGAGATCTTGGTAACCATGA                   CTGCAGTGCCCAGGATGCTCTCAGACCTGTTGGTCCCCCACAAAGTCATTACCTTCACTGGCTGCA                   TGGTCCAGTTCTACTTCCACTTTTCCCTGGGGTCCACCTCCTTCCTCATCCTGACAGACATGGCCC                   TTGATCGCTTTGTGGCCATCTGCCACCCACTGCGCTATGGCACTCTGATGAGCCGGGCTATGTGTG                   TCCAGCTGGCTGGGGCTGCCTGGGCAGCTCCTTTCCTAGCCATGGTACCCACTGTCCTCTCCCGAG                   CTCATCTTGATTACTGCCATGGCGACGTCATTAACCACTTCTTCTGTGACAATGAACCTCTCCTGC                   AGTTGTCATGCTCTGACACTCGCCTGTTGGAATTCTGGGACTTTCTGATGGTCTTGACCTTTGTCC                   TCAGCTCCTTCCTGGTGACCCTCATCTCCTATGGCTACATAGTGACCACTGTGCTGCAAATCCCCT                   CTGCCAGCAGCTGCCAGAAGGCTTTCTCCACTTGCGGGTCTCACCTCACACTGGTCTTCATCGGCT                   ACAGTAGTACCATCTTTCTGTATGTCAGGCCTGGCAAAGCTCACTCTGTGCAAGTCAGGAAGGTCG                   TGGCCTTGGTGACTTCAGTTCTCACCCCCTTTCTCAATCCCTTTATCCTTACCTTCTGCAATCAGA                   CAGTTAAAACAGTGCTACAGGGGCAGATAATAGAGGCTGAAAGGCCTTTGCAAAACACAATGATGAG                   CC                                         ORF Start: ATG at 21       ORF Stop: TAG at 954           SEQ ID NO:72   311 aa   MW at 34742.9 kD                     NOV18f,   MGGPILWIMANLSQPSEFVLLGFSSFGELQALLYGPFLMLYLLAFMGNTIIIVMVIADTHLHTPMY       CG50303-02       Protein Sequence   FAALGNFSLLEILVTTAVPRMLSDLLVPHKVITFTGCMVQFYAAHFSLGSTSFLILTDAADRAAAI                   CHPLRYGTLMSRAMCVQLAGAAWAAPFLAMVPTVLSRAHLDYCHGDVINHFFCDNEPLLQLSCSDT                   RLLEFWDFLMVLTFVLSSFLVTLISYGYIVTTVLRIPSASSCQKAFSTCGSHLTLVFIGYSSTIFL                   YVRPGKAHSVQVRKVVALVTSVLTPFLNPFILTFCNQTVKTVLGGQM                  
 
     [0452] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 18B.  
               TABLE 18B                          Comparison of NOV18a against NOV18b through NOV18f                                 Protein   NOV18a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV18b   9 . . . 311   303/303 (100%)               1 . . . 303   303/303 (100%)           NOV18c   9 . . . 311   303/303 (100%)               6 . . . 308   303/303 (100%)           NOV18d   46 . . . 296    250/251 (99%)                3 . . . 253   251/251 (99%)            NOV18e   1 . . . 311   311/311 (100%)               1 . . . 311   311/311 (100%)           NOV18f   1 . . . 311   310/311 (99%)                1 . . . 311   310/311 (99%)                       
 
     [0453] Further analysis of the NOV18a protein yielded the following properties shown in Table 18C.  
               TABLE 18C                       Protein Sequence Properties NOV18a                                        SignalP   Cleavage site between residues 58 and 59       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 0; pos. chg 0; neg. chg 0           H-region: length 16; peak value 8.74           PSG score: 4.34           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −2.13           possible cleavage site: between 31 and 32           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 5                                         INTEGRAL   Likelihood =   −7.11   Transmembrane    40-56           INTEGRAL   Likelihood =   −0.48   Transmembrane    68-84           INTEGRAL   Likelihood =   −0.37   Transmembrane   147-163           INTEGRAL   Likelihood =   −7.48   Transmembrane   206-222           INTEGRAL   Likelihood =   −2.28   Transmembrane   279-295           PERIPHERAL   Likelihood =    0.90   (at 117)                         ALOM score: −7.48 (number of TMSs: 5)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 47           Charge difference: 2.0 C(0.0)-N(−2.0)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt;Caution: Inconsistent mtop result with signal peptide           &gt;&gt;&gt; membrane topology: type 3b           MITDISC: discrimination of mitochondrial targeting seq                                         R content:   0   Hyd Moment (75):   2.02               Hyd Moment (95):   3.18   G content:   1           D/E content:   1   S/T content:   2                         Score: −5.78           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 4.5%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern : none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs:           Leucine zipper pattern (PS00029): *** found ***           LSCSDTRLLEFWDFLMALTFVL at 193           none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           44.4%: endoplasmic reticulum           22.2%: vacuolar           11.1%: Golgi           11.1%: vesicles of secretory system           11.1%: mitochondrial           &gt;&gt; prediction for CG50303-01 is end (k = 9)                  
 
     [0454] A search of the NOV18a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 18D.  
               TABLE 18D                          Geneseq Results for NOV18a                                         NOV18a   Identities/                   Residues/   Similarities       Geneseq   Protein/Organism/Length   Match   for the   Expect       Identifier   [Patent #, Date]   Residues   Matched Region   Value               ABG76789   Human G-protein coupled receptor   1 . . . 311   311/311 (100%)   e−180           (GPCR) protein #23 -  Homo sapiens ,   1 . . . 311   311/311 (100%)           321 aa. [WO200259313-A2,           01 AUG. 2002]       ABG76788   Human G-protein coupled receptor   1 . . . 311   311/311 (100%)   e−180           (GPCR) protein #22 -  Homo sapiens ,   21 . . . 331    311/311 (100%)           341 aa. [WO200259313-A2,           01 AUG. 2002]       ABG66926   Novel G-protein coupled receptor   1 . . . 311   311/311 (100%)   e−180           related protein #4 -  Mus musculus ,   7 . . . 317   311/311 (100%)           327 aa. [WO200240539-A2,           23 MAY. 2002]       AAU85292   G-coupled olfactory receptor #153 -   1 . . . 311   311/311 (100%)   e−180             Homo sapiens , 399 aa.   79 . . . 389    311/311 (100%)           [WO200198526-A2, 27 DEC. 2001]       ABG66928   Novel G-protein coupled receptor   1 . . . 311   310/311 (99%)    e−180           related protein #6 -  Mus musculus ,   1 . . . 311   310/311 (99%)            311 aa. [WO200240539-A2,           23 MAY 2002]                  
 
     [0455] In a BLAST search of public sequence databases, the NOV18a protein was found to have homology to the proteins shown in the BLASTP data in Table 18E.  
               TABLE 18E                          Public BLASTP Results for NOV18a                                         NOV18a   Identities/           Protein       Residues/   Similarities       Accession       Match   for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value               CAC69319   Sequence 1 from Patent   1 . . . 311   310/311 (99%)    e−179           WO0159117 -  Homo sapiens     79 . . . 389    310/311 (99%)           (Human), 399 aa.       Q8N148   Seven transmembrane helix   9 . . . 311    303/303 (100%)    e−174           receptor -  Homo sapiens     1 . . . 303    303/303 (100%)           (Human), 313 aa.       Q8NG79   Seven transmembrane helix   9 . . . 308   159/300 (53%)   1e−88           receptor -  Homo sapiens     1 . . . 298   212/300 (70%)           (Human), 313 aa.       Q96RR8   Olfactory receptor 6W1 (Olfactory   20 . . . 308    155/289 (53%)   2e−88           receptor sdolf) -  Homo sapiens     11 . . . 299    208/289 (71%)           (Human), 314 aa (fragment).       Q8NGD8   Seven transmembrane helix   46 . . . 308    143/263 (54%)   1e−81           receptor -  Homo sapiens     3 . . . 265   192/263 (72%)           (Human), 280 aa.                  
 
     [0456] PFam analysis predicts that the NOV18a protein contains the domains shown in the Table 18F.  
               TABLE 18F                          Domain Analysis of NOV18a                                     Identities/                   Similarities           NOV18a   for the   Expect       Pfam Domain   Match Region   Matched Region   Value               7tm_1   47 . . . 296    55/268 (21%)   4.3e−29               167/268 (62%)                  
 
     Example 19.  
     [0457] 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:73   1113 bp                     NOV19a,     AT   GAA TTAAACTCAATCGTGATGGTGGTGATGACCGGTACGCGTAGAATCGAGACCGAGGAGAGGG       CG54092-03       DNA Sequence   TTAGGGATAGGCTTACCCTCGACGATGGACTTCCACCGGGCCCCAAGCCTGGGAGCCTGCCCGCCA                   CGCACGACCCCCGGGCTCGACGGGGGCGAAAAGCCCAGGTTGTCGCGGGCGCACCTCTCCAGCTTG                   TGCACGTGGCAGAAGACACAGGCGGAGCCCACGGAGCGCGCCGGGCGGCGGGGCAGCCAGAGCCCA                   CGGCTCTCGGGCGCCCCCGGGGGGCGCGGGCTGGGGGTGCGGGCAGCGCGCTCGGGCCACTCGGCG                   CTGGCAACGAGGAAGCGCAGGACCACCAGGTTGAGGAAGGCGCCAATGACCGTGAGCCCCAGGAGG                   ATGTAGAGGAAGCTGAAGGCCACGTAGGGGAGCTTCCTCTGCAGCGCCTCGCCGCTCTGCAGTGCC                   ACGAAGTCGCCGAAGCCGATGGTGGTGAGGGTGATGAAGCAGTAGTAGTAGGCGTGGAAGAAGGTC                   CAGCCCTCGAAGTGCGAGAAGGCGACGGCCCCCACGGCCAGGGTGGCGGCACACGCCAGCAGCCCG                   GCCACCACCAGGTTCTCCGTGGACACGCACGTCCACCGCAGGCCCAGGCAGCACTTGGCCGCCAAC                   AGGAGGCGCCGCACCACCGCGTTCAGCCGTTCGCCCAGGCTCTGGAAAGTGACCAGCGTCAGCGGG                   ATGCCCAGGAGCGCGTAGAACATGCAGAAGACCTTGCCGGAGTCCGTACCCGGCGCGGCGTGGCCG                   TACTCGATGGTAGTGATGACGGTGATGGCGAAGTAGAAGGAGCCGGGGAACTTCCACTGGCGGCCG                   GCGCGGTGGGGCTCAGCCTGGAGCGCCAGGCGCTCCAGCTCGCGGTAGTCCTCGGCCGAGAAGCCG                   AACTTCCTCCGGAGAGCGCCCCGCTTCTGGACCAGCAGTCGCTGGCGGCCGCTTTCCGCCTCGGAC                   TCGAGCGCGTCGAAGACAGCAGCGCCCACCAGCAGGTAACACAGGGTGCACAGGACCAGCCCGGCC                   GCGCGCACGCTCCGCCTCCGCATGGTGGATCCTCCCGAAGATCTTCTGAAAAGCTTC                                         ORF Start: at 3       OFR Stop: at 1113           SEQ ID NO:74   370 aa   MW at 38623.0 kD                     NOV19a,   ELNSMVMVVMTGTRRIETEERVRDRLTLDDGLPPGPKPGSLPATHDPRARCGRKAQVVAGAPLQLV       CG54092-03       Protein Sequence   HVAEDRGGAHGAGRAACQPEATALGRPRGARAGGAGSALGPVGAGNEEAQDHQVEEGANDREPQED                   VEEAEGHVGELPLQRLAALQCHEVAEADGGEGDEAVVVGVEEGPALEVREGDGPEGGGGGTRQQPG                   HHQVLRGHARPPQAQAALGRQQEAPHHRVQPFAQALESDQRQRDAQERVEHAEDLAGVRTRRGVAV                   LDGSDDGDGEVEGAGELPLAAGAVGLSLERQALQLAVVLGREAELPPESAPLLDQQSLAAAFRLGL                   ERVEDSSAHQQVTGGAQDQPGRAHARPPHGGSSRRSSEKL                                     SEQ ID NO:75   1216 bp                     NOV19b,     ATG CGGAGGCCGAGCGTGCGCGCGGCCGGGCTGGTCCTGTGCACCCTGTGTTACCTGCTGGTGGGC       CG54092-01       DNA Sequence   GCTGCTGTCTTCGACGCGCTCGAGTCCGAGGCGGAAAGCGGCCGCCAGCGACTGCTGGTCCAGAAG                   CCGGGCGCTCTCCGGAGGAAGTTCGGCTTCTCGGCCGAGGACTACCGCGAGCTGGAGCGCCTGGCG                   CTCCACGCTGAGCCCCACCGCGCCGGCCGCCAGTGGAAGTTCCCCGGCTCCTTCTACTTCGCCATC                   ACCGTCATCACTACCATCGAGTACGGCCACGCCGCGCCGGGTACGGACTCCGGCAAGGTCTTCTGC                   ATGTTCTACGCGCTCCTGCGCATCCCGCTGACGCTGGTCACTTTCCAGAGCCTGGGCGAACGGCTG                   AACGCGGTGGTGCGGCGCCTCCTGTTGGCGGCCAAGTGCTGCCTGGGCCTGCGGTGGACGTGCGTG                   TCCACGGAGAACCTGGTGGTCGCCCGGCTGCTGGCGTGTGCCGCCACCCTGGCCCTCGGGGCCGTC                   GCCTTCTCGCACTTCGAGGGCTGGACCTTCTTCCACGCCTACTACTACTGCTTCATCACCCTCACC                   ACCATCGGCTTCGGCGACTTCGTGGCACTGCAGAGCGGCGAGGCGCTGCAGAGGAAGCTCCCCTAC                   GTGGCCTTCAGCTTCCTCTACATCCTCCTGGGCCTCACGGTCATTGGCGCCTTCCTCAACCTCGTG                   GTCCTGCGCTTCCTCGTTGCCAGCGCCGACTGGCCCGAGCGCGCTGCCCGCACCCCCAGCCCGCGC                   CCCCCGGGGGCGCCCGAGAGCCGTGGCCTCTGGCTGCCCCGCCGCCCGGCCCGCTCCGTGGGCTCC                   GCCTCTGTCTTCTGCCACGTGCACAAGCTGGAGAGGTGCGCCCGCGACAACCTGGGCTTTTCGCCC                   CCCTCGAGCCCGGGGGTCGTGCGTGGCGCGCAGGCTCCCAGGCTTGGGGCCCGGTGGAAGTCCATC                     TGA   CAACCCCACCCAGGCCAGGGTCGAATCTGGAATGGGAGGGTCTGGCTTCAGCTATCAGGGCAC                       CCTCCCCAGGGATTGGAAACGGATGACGGGCCTTTAGGCGGTTTTTTGCCACGAGCAGTTTTTCAT                       TACTGTCTGTCGCTAAGTCCCCTCCCTCCTTTCCAAAAATATATTACAGTCACCCCATAAGCCCAA                       AAAAAAAAAAAAA                                           ORF Start: ATG at 1       ORF Stop:TGA at 991           SEQ ID NO:76   330 aa   MW at 36221.8 kD                     NOV19b,   MRRPSVRAAGLVLCTLCYLLVGAAVFDALESEAESGRQRLLVQKRGALRRKFGFSAEDYRELERLA       CG54092-01       Protein Sequence   LQAEPHRAGRQWKFPGSFYFAITVITTIEYGHAAPGTDSGKVFCMFYALLGTPLTLVTFQSLGERL                   NAVVRRLLLAAKCCLGLRWTCVSTENLVVAGLLACAATLALGAVAFSHFEGWTFFHAYYYCFITLT                   TIGFGDFVALQSGEALQRKLPYVAFSFLYILLGLTVIGAFLNLVVLkFLVASADWPERAARTPSPR                   PPGAPESRGLWLPRRPARSVGSASVFCHVHKLERCARDNLGFSPPSSPGVVRGGQAPRLGARWKSI                                     SEQ ID NO:77   1113 bp                     NOV19c,     AT   GAA TTAAACTCAATGGTGATGGTGGTGATGACCGGTACGCGTAGAATCGAGACCGAGGAGAGGG       CG54092-03       DNA Sequence   TTAGGGATAGGCTTACCCTCGACGATGGACTTCCACCGGGCCCCAAGCCTGGGAGCCTGCCCGCCA                   CGCACGACCCCCGGGCTCGAGGGGGGCGAAAAGCCCAGGTTGTCGCGGGCGCACCTCTCCAGCTTG                   TGCACGTGGCAGAAGACAGAGGCCGAGCCCACGGAGCGGGCCGGGCGGCGGGGCAGCCAGAGGCCA                   CGGCTCTCGGGCGCCCCCGGGGGGCGCGGGCTGGGGGTGCGGGCAGCGCGCTCGGGCCAGTCGGCG                   CTGGCAACGAGGAAGCGCACGACCACCAGGTTGAGGAAGGCGCCAATGACCGTGAGCCCCAGGAGG                   ATGTAGAGGAAGCTGAAGGCCACGTAGGGGACCTTCCTCTGCAGCGCCTCGCCGCTCTGCAGTGCC                   ACGAAGTCGCCGAGCCGATGGTGGTGAGGGTGATGAAGCAGTAGTAGTAGGCGTGGAAGAACGTC                   CAGCCCTCGAAGTGCGAGAAGGCGACGGCCCCGAGGGCCAGGGTGGCGGCACACGCCAGCAGCCCG                   GCCACCACCAGGTTCTCCGTGGACACGCACGTCCACCGCAGGCCCAGCCAGCACTTGGCCGCCAAC                   AGGAGGCGCCGCACCACCGCGTTCAGCCGTTCGCCCAGGCTCTGGAAAGTGACCAGCGTCAGCGGG                   ATGCCCAGGAGCGCGTAGAACATGCAGAAGACCTTGCCCGAGTCCGTACCCGGCGCGGCGTGGCCG                   TACTCGATGGTAGTGATGACGGTGATGGCGAAGTAGAAGGAGCCGGGGAACTTCCACTGGCGGCCC                   GCGCGGTGGGGCTCAGCCTGGAGCGCCAGGCGCTCCAGCTCGCGGTAGTCCTCGGCCGAGAAGCCG                   AACTTCCTCCGGAGAGCGCCCCGCTTCTGGACCAGCAGTCGCTGGCGGCCGCTTTCCGCCTCGGAC                   TCGAGCGCGTCGAAGACAGCAGCGCCCACCAGCAGGTAACACAGGGTGCACAGGACCAGCCCGGCC                   GCGCGCACGCTCGGCCTCCGCATGGTGGATCCTCGCGAAGATCTTCTGAAAAGCTTC                                         ORF Start: at 3       ORF Stop: at 1113           SEQ ID NO:78   370 aa   MW at 38623.0 kD                     NOV19c,   ELNSMVMVVMTGTRRIETEERVRDRLTLDDGLPPGPKPGSLPATHDPRARGGRKAQVVAGAPLQLV       CG54092-03       Protein Sequence   HVAEDRGGAHGAGRAAGQPEATALGRPRGARAGCAGSALGPVGAGNEEAQDHQVEEGANDREPQED                   VEEAEGHVGELPLQRLAALQCHEVAEADGGEGDEAVVVGVEEGPALEVREGDGPEGGGGGTRQQPG                   MHQVLRGHARPPQAQAALGRQQEAPHHRVQPFAQALESDQRQRDAQERVEHAEDLAGVRTRRGVAV                   LDGSDDGDGEVEGAGELPLAAGAVGLSLERQALQLAVVLGREAELPPESAPLLDQQSLAAAFRLGL                   ERVEDSSANQQVTGGAQDQPGRAHARPPHGGSSRRSSEKL                                     SEQ ID NO:79   265 bp                     NOV19d,     GCC GTCGACAAAGTCCGTACCCAACGCAACGTGGCCGTACCCGATAATAGTGATGACGGTGATGGC       262770591 DNA       Sequence   CAAGTAGAAGGAGCCGGGGAACTTCCACTGGCGGCCGGCGCGGTGGGGCTCAGCCTGGAGCGCCAG                   GCGCTCCAGCTCGCGGTAGTCCTCGGCCGAGAAGCCGAACTTCCTCCCGAGAGCGCCCCGCTTCTG                   GACCAGCAGTCGCTGGCGGCCGCTTTCCGCCTCGGACTCGAGCGCGTCGAAGACAGCGGATCCGGT                                         ORF Start: at 1       ORF Stop: end of sequence           SEQ ID NO:80   89 aa   MW at 8876.7 kD                     NOV19d,   AVDGVRTRRGVAVPDGSDDGDGEVEGAGELPLAAGAVGLSLERQALQLAVVLGREAELPPESAPLL       262770591       Protein Sequence   DQQSLAAAFRLGLERVEDSGSGX                                     SEQ ID NO:81   265 bp                     NOV19e,     GCC GTCGACGGAGTCCGTACCCGGCGCGGCGTGGCCGTACTCGATGGTAGTGATGACGGTGATGGC       262770609 DNA       Sequence   GAAGTAGAAGGAGCCGGGGAACTTCCACTGGCGCCCGGCGCGGTGGGGCTCAGCCTGGAGCGCCAG                   GCGCTCCAGCTCGCGGTAGTCCTCGGCCGAGAACCCGAACTTCCTCCGGAGAGCGCCCCGCTTCTG                   GACCAGCAGTCGCTGGCGGCCGCTTTCCGCCTCGGACTCGAGCGCGTCGAAGACAGCGGATCCGGT                                         ORF Start: at 1       ORF Stop: end of sequence           SEQ ID NO:82   89 aa   MW at 8892.7 kD                     NOV19e,   AVDGVRTRRGVAVLDGSDDGDGEVEGAGELPLAAGAVGLSLERQALQLAVVLGREAELPPESAPLL       262770609       Protein Sequence   DQQSLAAAFRLGLERVEDSGSGX                                     SEQ ID NO:83   1113 bp                     NOV19f     AT   GAA TTAAACTCAATGGTGATGGTGGTGATGACCGGTACGCGTAGAATCGAGACCGAGGAGAGGG       296457330 DNA       Sequence   TTAGGGATAGGCTTACCCTCGACGATGGACTTCCACCGGGCCCCAAGCCTGGGAGCCTGCCCGCCA                   CGCACGACCCCCGGGCTCGAGGGGGGCGAAAAGCCCAGGTTGTCGCGGGCGCACCTCTCCAGCTTG                   TGCACGTGGCAGAAGACAGAGGCGGAGCCCACGGAGCGGGCCGGGCGGCGGGGCAGCCAGAGGCCA                   CGGCTCTCGGGCGCCCCCGGGGGGCGCGGGCTGGCGGTGCGGGCAGCGCGCTCGGGCCAGTCGGCG                   CTGGCAACGAGGAAGCGCAGGACCACCAGGTTGAGGAAGGCGCCAATGACCGTGAGCCCCAGGAGG                   ATGTAGAGGAAGCTGAAGGCCACGTAGGGGAGCTTCCTCTGCAGCGCCTCGCCGCTCTGCAGTGCC                   ACGAAGTCGCCGAAGCCGATGGTGGTGAGGGTGATGAAGCAGTAGTAGTACGCGTGGAAGAAGGTC                   CAGCCCTCGAAGTGCGAGAAGGCGACGGCCCCGAGGGCCAGGGTGGCGGCACACGCCAGCAGCCCG                   GCCACCACCAGGTTCTCCGTGGACACGCACGTCCACCGCAGGCCCAGGCAGCACTTGGCCGCCAAC                   AGGAGGCGCCGCACCACCGCGTTCAGCCGTTCGCCCAGGCTCTGGAAAGTGACCAGCGTCAGCGGG                   ATGCCCAGGAGCCCGTAGAACATGCAGAAGACCTTGCCGGAGTCCGTACCCGGCGCGGCGTGGCCG                   TACTCGATGGTAGTGATGACGAAGATGGCGAAGTAGAAGGAGCCGGGGAACTTCCACTGGCGGCCG                   GCGCGGTGGGGCTCAGCCTGGAGCGCCAGGCGCTCCAGCTCGCGGTAGTCCTCGGCCGAGAAGCCG                   AACTTCCTCCGGAGAGCGCCCCGCTTCTGGACCAGCAGTCGCTGGCGGCCGCTTTCCGCCTCGGAC                   TCGAGCGCGTCGAAGACAGCAGCGCCCACCAGCAGGTAACACAGGGTGCACAGGACCAGCCCCGCC                   GCGCGCACGCTCGGCCTCCGCATGGTGGATCCTCGCGAACATCTTCTGAAAAGCTTC                                         ORF Start: at 3       ORF Stop: end of sequence           SEQ ID NO:84   371 aa   MW at 38623.0 kD                     NOV19f,   ELNSMVMVVMTGTRRIETEERVRDRLTLDDGLPPGPKPGSLPATHDPRARGGRKAQVVAGAPLQLV       29645330       Protein Sequence   HVAEDRGGAHGAGRAAGQPEATALGRPRGARAGGAGSALGPVGAGNEEAQDHQVEEGANDREPQED                   VEEAEGHVGELPLQRLAALQCHEVAEADGGEGDEAVVVGVEEGPALEVREGDGPEGGGGGTRQQPG                   HHQVLRGHARPPQAQAALGRQQEAPHHRVOPFAQALESDQRQRDAQERVEHAEDLAGVRTRRGVAV                   LDGSDDGDGEVEGAGELPLAAGAVGLSLERQALQLAVVLGREAELPPESAPLLDQQSLAAAFRLGL                   ERVEDSSAHQQVTQCAQDQPGRAHARPPHGGSSRRSSEKLX                                     SEQ ID NO:85   265 bp                     NOV19g,     CACCGGATCC   GCT GTCTTCGACGCGCTCGAGTCCGAGGCGGAAAGCGGCCGCCAGCGACTGCTGGT       CG54092-02       DNA Sequence   CCAGAAGCGGGGCGCTCTCCGGAGGAAGTTCGGCTTCTCGGCCGAGGACTACCGCGAGCTGGAGCG                   CCTGGCGCTCCAGGCTGAGCCCCACCGCGCCGGCCGCCAGTGGAAGTTCCCCGGCTCCTTCTACTT                   CGCCATCACCGTCATCACTACCATCGGGTACGGCCACGCCGCGCCGGGTACGGACTCCGTCGACGGC                                         ORF Start: at 11       ORF Stop: end of sequence           SEQ ID NO:86   85 aa   MW at 9472.5 kD                     NOV19g,   AVFDALESEAESGRQRLLVQKRGALRKFGFSADYRELERLLQAEPAAAGRQWKFPGSFYFAIT       CG54092-02       Protein Sequence   VITTIGYGHAAPGTDSVDG                  
 
     [0458] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 19B.  
               TABLE 19B                          Comparison of NOV19a against NOV19b through NOV19g                                 Protein   NOV19a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV19b   58 . . . 126    19/69 (27%)               234 . . . 302    24/69 (34%)           NOV19c   1 . . . 370   370/370 (100%)                1 . . . 370   370/370 (100%)            NOV19d   255 . . . 338    81/84 (96%)               4 . . . 87    82/84 (97%)           NOV19e   255 . . . 338    82/84 (97%)               4 . . . 87    83/84 (98%)           NOV19f   1 . . . 370   370/370 (100%)                1 . . . 370   370/370 (100%)            NOV19g   292 . . . 298     6/7 (85%)               39 . . . 45     6/7 (85%)                      
 
     [0459] Further analysis of the NOV19a protein yielded the following properties shown in Table 19C.  
               TABLE 19C                       Protein Sequence Properties NOV19a                                        SignalP   No Known Signal Sequence Predicted       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 1; pos. chg 0; neg. chg 1           H-region: length 12; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −9.10           possible cleavage site: between 18 and 19           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 3.23 (at 287)           ALOM score: 3.23 (number of TMSs: 0)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   2   Hyd Moment(75):   1.38           Hyd Moment(95):   2.09   G content:   1           D/E content:   2   S/T content:   3                         Score: −5.92           Gavel: prediction of cleavage sites for mitochondrial preseq           R-2 motif at 25 RRI|ET           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 10.3%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           KKXX-like motif in the C-terminus: SSEK           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern : none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 76.7           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23) :           69.6%: cytoplasmic           17.4%: nuclear            4.3%: mitochondrial            4.3%: plasma membrane            4.3%: peroxisomal           &gt;&gt; prediction for CG54092-03 is cyt (k = 23)                  
 
     [0460] 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 19D.  
               TABLE 19D                          Geneseq Results for NOV19a                                         NOV19a   Identities/                   Residues/   Similarities       Geneseq   Protein/Organism/Length   Match   for the   Expect       Identifier   [Patent #, Date]   Residues   Matched Region   Value               AAE13147   Human retinitis pigmentosa GTPase   109 . . . 280    44/180 (24%)   1e−04           regulator (RPGR) exon ORF15 -  Homo     248 . . . 427    70/180 (38%)             sapiens , 567 aa. [WO200177380-A2,           18 OCT. 2001]       AAE02397   Canine retinitis pigmentosa GTPase   68 . . . 280   53/218 (24%)   5e−04           regulator (RPGR) protein -  Canis     254 . . . 437    80/218 (36%)             familiaris , 522 aa. [WO200138578-A1,           31 MAY 2001]       ABG04359   Novel human diagnostic protein   70 . . . 187   35/124 (28%)   8e−04           #4350 -  Homo sapiens , 508 aa.   251 . . . 367    50/124 (40%)           [WO200175067-A2, 11 OCT. 2001]       AAB23158   Human colorectal cancer modulator   33 . . . 201   49/196 (25%)   0.007           protein, CAA9 -  Homo sapiens , 1212    8 . . . 197   62/196 (31%)           aa. [WO200055633-A2, 21 SEP. 2000]       ABG32328     P. vivax  circumsporozoite protein   30 . . . 127   40/106 (37%)   0.012           derived hypothetical protein -   23 . . . 120   43/106 (39%)             Plasmodium vivax  strain Belem, 144           aa. [US6399062-B1, 04 JUN. 2002]                  
 
     [0461] In a BLAST search of public sequence databases, the NOV19a protein was found to have homology to the proteins shown in the BLASTP data in Table 19E.  
               TABLE 19E                          Public BLASTP Results for NOV19a                                         NOV19a   Identities/           Protein       Residues/   Similarities       Accession       Match   for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value               Q9GMD3   X-linked retinitis pigmentosa GTPase    70 . . . 280   55/218 (25%)   2e−05           regulator -  Bos taurus  (Bovine), 934   498 . . . 707   78/218 (35%)           aa (fragment).       Q918P0   Latency associated antigen - Ovine    74 . . . 286   59/226 (26%)   5e−05           herpesvirus 2, 495 aa.   140 . . . 334   79/226 (34%)       Q9ET15   Retinitis pigmentosa GTPase    46 . . . 280   59/241 (24%)   5e−05           regulator -  Mus musculus  (Mouse),   141 . . . 377   94/241 (38%)           538 aa (fragment).       Q9HD28   Retinitis pigmentosa GTPase   109 . . . 280   44/180 (24%)   4e−04           regulator -  Homo sapiens  (Human),   248 . . . 427   70/180 (38%)           567 aa (fragment).       Q03871   Glutenin, high molecular weight    77 . . . 229   40/160 (25%)   5e−04           subunit 1BY9 precursor -  Triticum     240 . . . 380   64/160 (40%)             aestivum  (Wheat), 705 aa.                  
 
     [0462] PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19F.  
               TABLE 19F                       Domain Analysis of NOV19a                                                Pfam Domain   NOV19a   Identities/Similarities   Expect           Match Region   for the Matched Region   Value                  
 
     Example 20.  
     [0463] 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:87   953 bp                     NOV20a,     CTCTGCC   ATG ATCATTTTCAACCTGAGCAGTTACAATCCAGGACCCTTCATTCTGGTAGGGATCCC       CG55798-04       DNA Sequence   AGGCCTGGAGCAATTCCATGTGTGGATTGGAATTCCCTTCTGTATCATCTACATTGTAGCTGTTGT                   GGGAAACTGCATCCTTCTCTACCTCATTGTGGTGGAGCATAGTCTTCATGAACCCATGTTCTTCTT                   TCTCTCCATGCTGGCCATGACTGACCTCATCTTGTCCACAGCTGGTGTGCCTAAAACACTCAGTAT                   CTTTTGGCTAGGGGCTCGCCAAATCACATTCCCAGGATGCCTTACACAAATGTTCTTCCTTCACTA                   TAACTTTGTCCTGGATTCAGCCATTCTGATGGCCATGGCATTTGATCACTATGTAGCTATCTGTTC                   TCCCTTGAGATATACCACCATCTTGACTCCCAAGACCATCATCAAGAGTGCTATGGGCATCTCCTT                   TCGAAGCTTCTGCATCATCCTGCCAGATGTATTCTTGCTGACATGCCTGCCTTTCTGCAGGACACG                   CATCATACCCCACACATACTGTGAGCATATGGGTGTTCCCCAGCTCGCCTGTGCTGATATCTCCAT                   CAACTTCTGGTATGGCTTTTGTGTTCCCATCATGACAGTCATCTCAGATGTGATTCTCATTGCTGT                   TTCCTACGCACACATCCTCTGTGCTGTCTTTTGCCTTCCCTCCCAAGATGCCCGCCAGAAGGCCCT                   CGGCACTTGTGOTTCTCATGTCTGTGTCATCCTCATGTTTTATACACCTGCCTTTTTCTCCATCCT                   CGCCCATCGCTTTGGACACAATGTCTCTCGCACCTTCCACATCATGTTTGCCAATCTCTACATTGT                   TATCCCACCTCCACTCAACCCCATGGTTTACGGAGTGAAGACCAAGCAGATCAGAGATAAGGTTAT                   ACTTTTGTTTTCTAAGGGTACAGGA TGA T                                             ORF Start: ATG at 8       ORF Stop: TGA at 950           SEQ ID NO:88   314 aa   MW at 35193.8 kD                     NOV20a,   MIIFNLSSYNPGPFILVGIPGLEQFHVWIGIPFCIIYIVAVVAGNCILLYLIVVEHSLHEPMFFFLS       CG55798-04       Protein Sequence   MLAMTDLILSTAGVPKTLSIFWLGAREITFPGCLTQMFFLHYNFVLDSAILMAMAFDHYVAICSPL                   RYTTILTPKTILLKSAMGISFRSFCIILPDVFLLTCLPFCRTRIIPHTYCEHMGVAQLACADISINF                   WYGFCVPIMTVISDVILIAVSYAHILCAVFCLPSQDARQKALGTCGSHVCVILMFYTPAFFSILAH                   RFGHNVSRTFHIMFANLYIVIPPALNPMVYGVKTKQIRDKVILLFSKGTG                                     SEQ ID NO:89   938 bp                     NOV20b,     TAA   ATG ATGGACAACCACTCTAGTGCCACTGAATTCCACCTTCTAGGCTTCCCTGGGTCCCAAGGA       CG55798-02       DNA Sequence   CTACACCACATTCTTTTTCCTATATTCTTTTTCTTCTATTTAGTGACATTAATGGGAAACACGGTC                   ATCATTGTGATTGTCTGTGTGGATAAACGTCTGCAGTCCCCCATGTATTTCTTCCTCACCCACCTC                   TCTACCCTGGAGATCCTCGTCACAACCATAATTGTCCCCATGATGCTTTGGGGATTGCTCTTCCTG                   GGATGCAGACAGTATCTTTCTCTACATGTATCCCTCAACTTTTCCTGTGGGACCATGGAGTTTGCA                   TTACTTGGAGTGATGGCTGTGGACCGTTATGTGGCTGTGTGTAACCCTTTGAGGTACAACATCATT                   ATGAACAGCAGTACCTGTATTTGGGTGGTAATAGTGTCATGGGTGTTTCGATTTCTTTCTGAAATC                   TGGCCCATCTATGCCACATTTCAOTTTACCTTCCGCAAATCAAATTCATTAGACCATTTTTACTGT                   GACCGACGCCAATTGCTCAAACTGTCCTGCCATAACACTCTTCTCACAGAGTTTATCCTTTTCTTA                   ATGGCTGTTTTTATTCTCATTGGTTCTTTGATCCCTACGATTGTCTCCTACACCTACATTATCTCC                   ACCATCCTCAAGATCCCGTCAGCCTCTGGCCGGAGGAAAGCCTTCTCCACTTTTGCCTCCCACTTC                   ACCTGTGTTGTGATTGGCTATCGCAGCTGCTTGTTTCTCTACGTGAAACCCAAGCAAACACACCGA                   GTTGAGTACAATAAGATAGTTTCCCTGTTGGTTTCTGTGTTAACCCCCTTCCTGAATCCTTTCATC                   TTTACTCTTCGGAATGACAAAGTCAAAGAGGCCCTCCGAGATGGGATGAAACGCTGCTGTCAACTC                   CTGAAAGAT TAG   CT                                           ORF Start: ATG at 4       ORF Stop: TAG at 934           SEQ ID NO:90   310 aa   MW at 35329.6 kD                     NOV20b,   MMDNHSSATEFHLLGFPGSQGLHHILFAIFFFFYLVTLMGNTVIIVIVCVDKRLQSPMYFFLSHLS       CG55798-02       Protein Sequence   TLEILVTTIIVPMMLWGLLFLGCRQYLSLHVSLNFSCCTMEFALLGVMAVDRYVAVCNPLRYWIIM                   NSSTCIWVVIVSWVFGFLSEIWPIYATFQFTFRKSNSLDHFYCDRGOLLKLSCUNTLLTEFILFLM                   AVFILIGSLIPTIVSYTYIISTILKIPSASGRRKAFSTFASHFTCVVIGYGSCLFLYVKPKQTQGV                   EYNKIVSLLVSVLTPFLNPFIFTLRNDKVKEALRDGMKRCCQLLKD                                     SEQ ID NO:91   952 bp                     NOV20c,   CACCGGATCCACCAATGAGGACAACCACTCTAGTGCCACTGAATTCCACCTTCTAGGCTTCCCTGG       265722099 DNA       Sequence   GTCCCAAGOACTACACCACATTCTTTTTGCTATATTCTTTTTCTTCTATTTAGTGACATTAATGGG                   AAACACGGTCATCATTGTGATTGTCTGTGTGGATAAACGTCTGCAGTCCCCCATGTATTTCTTCCT                   CAGCCACCTCTCTACCCTGGAGATCCTGGTCACAACCATAATTGTCCCCATGATGCTTTGGGGATT                   GCTCTTCCTGGGATGCAGACAGTATCTTTCTCTACATGTATCGCTCAACTTTTCCTGTCGGACCAT                   GGAGTTTGCATTACTTGGAGTGATGGCTGTGGACCGTTATGTGGCTGTGTGTAACCCTTTGAGGTA                   CAACATCATTATGAACAGCAGTACCTGTATTTGGGTGGTAATAGTGTCATGGGTGTTTGGATTTCT                   TTCTGAAATCTGGCCCATCTATGCCACATTTCAGTTTACCTTCCGCAAATCAAATTCATTAGACCA                   TTTTTACTGTGACCGAGGGCAATTGCTCAAACTGTCCTGCGATAACACTCTTCTCACAGAGTTTAT                   CCTTTTCTTAATGGCTGTTTTTATTCTCATTGGTTCTTTGATCCCTACGATTGTCTCCTACACCTA                   CATTATCTCCACCATCCTCAAGATCCCGTCAGCCTCTGGCCGCAGGAAAGCCTTCTCCACTTTTGC                   CTCCCACTTCACCTGTGTTGTGATTGGCTATGGCAGCTGCTTGTTTCTCTACGTGAAACCCAAGCA                   AACACAGGGAGTTCAGTACAATAAGATAGTTTCCCTGTTGGTTTCTGTGTTAACCCCCTTCCTGAA                   TCCTTTCATCTTTACTCTTCGGAATGACAAAGTCAAAGAGGCCCTCCGAGATGGGATGAAACGCTG                   CTGTCAACTCCTGAAAGATCTCGAGGGC                                         ORF Start: at 2       ORF Stop: end of sequence           SEQ ID NO:92   317 aa   MW at 35956.1 kD                     NOV20c,   TGSTNEDNHSSATEFHLLGFPGSQGLHHILFAIFFFFYLVTLMGNTVIIVIVCVDKRLQSPMYFFL       265722099       Protein Sequence   SHLSTLEILVTTIIVPMMLWGLLFLGCRQYLSLHVSLNFSCGTMEFALLGVMAVDRYVAVCNPLRY                   NIIMNSSTCIWVVIVSWVFGFLSEIWPIYATFQFTFRKSNSLDHFYCDRGQLLKLSCDNTLLTEFI                   LFLMAVFILIGSLIPTIVSYTYIISTILKIPSASGRRKAFSTFASHFTCVVIGYGSCLFLYVKPKQ                   TQGVEYNKIVSLLVSVLTPFLNPFIFTLRNDKVKEALRDGMKRCCQLLKDLEG                                     SEQ ID NO:93   829 bp                     NOV20d,   CACCGGATCCAACACGGTCATCATTGTGATTGTCTGTGTGGATAAACGTCTGCAGTCCCCCATGTA       265725302 DNA       Sequence   TTTCTTCCTCAGCCACCTCTCTACCCTGGAGATCCTGGTCACAACCATAATTGTCCCCATGATGCT                   TTGGGGATTGCTCTTCCTGGGATGCAGACAGTATCTTTCTCTACATGTATCGCTCAACTTTTCCTG                    TGGGACCATGGAGTTTGCATTACTTGGAGTGATGGCTGTGGACCGTTATGTGGCTGTGTGTAACCC                   TTTGAGGTACAACATCATTATGAACACCACTACCTGTATTTGGGTGGTAATAGTGTCATGGGTGTT                   TGGATTTCTTTCTGAAATCTGGCCCATCTATGCCACATTTCAGTTTACCTTCCGCAAATCAAATTC                   ATTAGACCATTTTTACTGTGACCGAGGOCAATTGCTCAAACTGTCCTGCGATAACACTCTTCTCAC                   AGAGTTTATCCTTTTCTTAATGGCTGTTTTTATTCTCATTGGTTCTTTGATCCCTACGATTGTCTC                   CTACACCTACATTATCTCCACCATCCTCAAGATCCCGTCAGCCTCTGGCCGGAGGAAAGCCTTCTC                   CACTTTTGCCTCCCACTTCACCTGTGTTGTGATTGGCTATCGCACCTGCTTGTTTCTCTACGTGAA                   ACCCAAGCAAACACAGGGAGTTGAGTACAATAAGATAGTTTCCCTGTTGGTTTCTGTGTTAACCCC                   CTTCCTGAATCCTTTCATCTTTACTCTTCGGAATGACAAAGTCAAAGAGGCCCTCCGAGATGGGAT                   GAAACGCTGCTGTCAACTCCTGAAAGATCTCGAGGGC                                         ORF Start: at 2       ORF Stop: end of sequence           SEQ ID NO:94   276 aa   MW at 31316.9 kD                     NOV20d,   TGSNTVIIVIVCVDKRLQSPMYFFLSHLSTLEILVTTIIVPMMLWGLLFLGCRQYLSLNVSLNFSC       265725302       Protein Sequence   GTMEFALLGVMAVDRYVAVCNPLRYNIIMNSSTCIWVVIVSWVFGFLSEIWPIYATFQFTFRKSNS                   LDHFYCDRGQLLKLSCDNTLLTEFILFLMAVFILIGSLIPTIVSYTYIISTILKIPSASGRRKAFS                    TFASHFTCVVTQYGSCLFLYVKPKQTQGVEYNKIVSLLVSVLTPFLNPFIFTLRNDKVKEALRDGM                   KRCCQLLKDLEG                                     SEQ ID NO:95   953 bp                     NOV20e,     CTCTGCC ATGATCATTTTCAACCTGAGCAGTTACAATCCAGGACCCTTCATTCTGGTAGGGATCCC       CG55798-01       DNA Sequence   AGCCCTGGAGCAATTCCATGTGTGGATTGGAATTCCCTTCTGTATCATCTACATTGTAGCTGTTGT                   GGGAAACTGCATCCTTCTCTACCTCATTGTGGTGGAGCATAGTCTTCATGAACCCATCTTCTTCTT                   TCTCTCCATGCTGCCCATCACTGACCTCATCTTGTCCACACCTGGTGTGCCTAAAACACTCAGTAT                   CTTTTGGCTAGGGGCTCGCGAAATCACATTCCCAGGATGCCTTACACAAATGTTCTTCCTTCACTA                   TAACTTTGTCCTGGATTCAGCCATTCTGATGGCCATGGCATTTCATCGCTATGTACCTATCTGTTC                   TCCCTTGAGATATACCACCATCTTGACTCCCAAGACCATCATCAAGAGTGCTATGCGCATCTCCTT                   TCGAAGCTTCTGCATCATCCTGCCACATGTATTCTTGCTOACATGCCTGCCTTTCTGCACGACACG                   CATCATACCCCACACATACTGTGAGCATATAGGTGTTGCCCAGCTCGCCTGTCCTGATATCTCCAT                   CAACTTCTGGTATGGCTTTTGTGTTCCCATCATGACAGTCATCTCAGATGTGATTCTCATTGCTGT                   TTCCTACCCACACATCCTCTGTGCTGTCTTTTGCCTTCCCTCCCAAGATGCCCGCCACAAAGCCCT                   CGCCCATCGCTTTGGACACAATGTCTCTCGCACCTTCCACATCATGTTTGCCAATCTCTACATTGT                   CGCCCATCGCTTTGGACACAATGTCTCTCGCACCTTCCACATCATGTTTGCCAATCTCTACATTGT                   TATCCCACCTGCACTCAACCCCATGGTTTACGCAGTGAACACCAAGCAGATCAGACATAAGGTTAT                   ACTTTTGTTTTCTAAGGGTACAGGA TGA   T                                           ORF Start: ATG at 8       ORF Stop: TGA at 950           SEQ ID NO:96   314 aa   MW at 35194.8 kD                     NOV20e,   MIIFNLSSYNPGPFILVGIPGLEQFHVWIGIPFCIIYIVAVVGNCILLYLIVVEHSLHEPMFFFLS       CG55798-01       Protein Sequence   MLAMTDLILSTAGVPKTLSIFWLGAREITFPGCLTQMFFLHYNFVLDSAILMAMAFDRYVAICSPL                   RYTTILTPKTIIKSAMGISFRSFCIILPDVFLLTCLPFCRTRIIPHTYCEHIGVAQLACADISINF                   WYGFCVPIMTVISDVILIAVSYAHILCAVFCLPSQDARQKALGTCGSHVCVILMFYTPAFFSILAH                   RFGHNVSRTFHIMFANLYIVIPPALNPMVYGVKTKQIRDKVILLFSKGTG                                     SEQ ID NO:97   953 bp                     NOV20f,     CTCTGCC   ATG ATCATTTTCAACCTGAGCAGTTACAATCCAGGACCCTTCATTCTCGTAGGGATCCC       CG55798-03       DNA Sequence   AGGCCTGGAGCAATTCCATGTGTGGATTGOAATTCCCTTCTGTATCATCTACATTGTAGCTGTTGT                   GCGAAACTGCATCCTTCTCTACCTCATTOTGGTGGAGCATAGTCTTCATGAACCCATGTTCTTCTT                   TCTCTCCATGCTGCCCATGACTGACCTCATCTTGTCCACAGCTGGTGTGCCTAAAACACTCAGTAT                   CTTTTGGCTAGOGGCTCGCGAAATCACATTCCCAGGATGCCTTACACAAATGTTCTTCCTTCACTA                   TAACTTTGTCCTCGATTCAGCCATTCTGATGGCCATGGCATTTGATCGCTATGTAGCTATCTGTTC                   TCCCTTGAGATATACCACCATCTTGACTCCCAAGACCATCATCAAGAGTGCTATGGGCATCTCCTT                   TCGAAGCTTCTGCATCATCCTGCCAGATGTATTCTTGCTGACATCCCTGCCTTTCTGCAGGACACG                   CATCATACCCCACACATACTGTGAGCATATAGGTGTTGCCCGGCTCGCCTGTGCTGATATCTCCAT                   CAACTTCTGGTATGGCTTTTGTGTTCCCATCATGACAGTCATCTCAGATGTGATTCTCATTGCTGT                   TTCCTACGCACACATCCTCTGTGCTGTCTTTTGCCTTCCCTCCCAAGATGCCCGCCAGAAAGCCCT                   CCGCACTTGTGOTTCTCATGTCTGTGTCATCCTCATGTTTTATACACCTGCCTTTTTCTCCATCCT                   CGCCCATCGCTTTCGACACAATGTCTCTCCCACCTTCCACATCATGTTTGCCAATCTCTACATTGT                   TATCCCACCTGCACTCAACCCCATGGTTTACGGAGTGAAGACCAAGCAGATCAGAGATAAGGTTAT                   ACTTTTGTTTTCTAAGGGTACAGGATGAT                                         ORF Start: ATG at 8       ORF Stop: TGA at 950           SEQ ID NO:98   314 aa   MW at 35222.9 kD                     NOV20f,   MIIFNLSSYNPGPFILVGIPGLEQFHVWIGIPFCIIYIVAVVGNCILLYLIVVEHSLHEPMFFFLS       CG55798-03       Protein Sequence   MLAMTDLILSTAGVPKTLSIFWLGAREITFPGCLTQMFFLHYNFVLDSAILMAMAFDRYVAICSPL                   RYTTILTPKTIIKSAMGISFRSFCIILPDVFLLTCLPFCRTRIIPHTYCEHIGVARLACADISINF                   WYGFCVPIMTVISDVILIAVSYAHILCAVFCLPSQDARQKALGTCGSHVCVILMFYTPAFFSILAH                   RFGHNVSRTFHIMFANLYIVIPPALNPMVYGVKTKQIRDKVILLFSKGTG                  
 
     [0464] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 20B.  
               TABLE 20B                          Comparison of NOV20a against NOV20b through NOV20f                                         Identities/                   Similarities for           Protein   NOV20a Residues/   the Matched           Sequence   Match Residues   Region                       NOV20b   14 . . . 303    78/295 (26%)               11 . . . 295   146/295 (49%)           NOV20c   14 . . . 303    78/295 (26%)               15 . . . 299   146/295 (49%)           NOV20d   44 . . . 303    66/262 (25%)                4 . . . 258   133/262 (50%)           NOV20e    1 . . . 314   312/314 (99%)                1 . . . 314   313/314 (99%)           NOV20f    1 . . . 314   311/314 (99%)                1 . . . 314   313/314 (99%)                      
 
     [0465] Further analysis of the NOV20a protein yielded the following properties shown in Table 20C.  
               TABLE 20C                       Protein Sequence Properties NOV20a                                        SignalP   Cleavage site between residues 44 and 45       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 0; pos. chg 0; neg. chg 0           H-region: length 22; peak value 8.96           PSG score: 4.56           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −7.41           possible cleavage site: between 47 and 48           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 6                                         INTEGRAL   Likelihood =   −9.24   Transmembrane    35-51           INTEGRAL   Likelihood =   −1.17   Transmembrane    61-77           INTEGRAL   Likelihood =   −5.31   Transmembrane   155-171           INTEGRAL   Likelihood =   −0.16   Transmembrane   194-210           INTEGRAL   Likelihood =   −7.80   Transmembrane   213-229           INTEGRAL   Likelihood =   −5.36   Transmembrane   247-263                                 PERIPHERAL   Likelihood =     1.06 (at 116)                         ALOM score: −9.24 (number of TMSs: 6)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 42           Charge difference: −0.5 C(−1.0)-N(−0.5)           N &gt;= C: N-terminal side will be inside           &gt;&gt;&gt; membrane topology: type 3a           MITDISC: discrimination of mitochondrial targeting seq                                         R content:   0   Hyd Moment(75):   4.03               Hyd Moment(95):   2.58   G content:   3           D/E content:   1   S/T content:   2                         Score: −6.52           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 5.4%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:           KKXX-like motif in the C-terminus: SKGT           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           55.6%: endoplasmic reticulum           22.2%: mitochondrial           11.1%; nuclear           11.1%: vesicles of secretory system           &gt;&gt; prediction for CG55798-04 is end (k = 9)                  
 
     [0466] A search of the NOV20a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 20D.  
               TABLE 20D                          Geneseq Results for NOV20a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV20a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value                                         ABJ04720   GPCR 1 protein SEQ ID No 6 -   1 . . . 314    314/314 (100%)   0.0           Unidentified, 314 aa.   1 . . . 314    314/314 (100%)           [WO200246229-A2, 13 JUN. 2002]       ABJ04718   GPCR 1 protein SEQ ID No 2 -   1 . . . 314   312/314 (99%)   0.0           Unidentified, 316 aa.   3 . . . 316   313/314 (99%)           [WO200246229-A2, 13 JUN. 2002]       ABJ04719   GPCR 1 protein SEQ ID No 4 -   1 . . . 314   311/314 (99%)   0.0           Unidentified, 314 aa.   1 . . . 314   313/314 (99%)           [WO200246229-A2, 13 JUN. 2002]       ABJ03990   Human G-protein coupled receptor   1 . . . 314   310/314 (98%)   0.0           SEQ ID NO: 46 -  Homo sapiens , 320   7 . . . 320   311/314 (98%)           aa. [WO200255558-A2,           18 JUL. 2002]       AAU85271   G-coupled olfactory receptor #132 -   1 . . . 314   310/314 (98%)   0.0             Homo sapiens , 320 aa.   7 . . . 320   311/314 (98%)           [WO200198526-A2, 27 DEC. 2001]                  
 
     [0467] In a BLAST search of public sequence databases, the NOV20a protein was found to have homology to the proteins shown in the BLASTP data in Table 20E.  
               TABLE 20E                          Public BLASTP Results for NOV20a                                             Identities/           Protein           Similarities for       Accession       NOV20a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value               CAD37688   Sequence 411 from Patent   1 . . . 314   310/314 (98%)   0.0           WO0224726 -  Homo sapiens     1 . . . 314   311/314 (98%)           (Human), 314 aa.       Q8NGJ2   Seven transmembrane helix   1 . . . 314   310/314 (98%)   0.0           receptor -  Homo sapiens  (Human),   7 . . . 320   311/314 (98%)           320 aa.       Q8VG19   Olfactory receptor MOR31-12 -   1 . . . 310   279/310 (90%)   e-165             Mus musculus  (Mouse), 316 aa.   1 . . . 310   294/310 (94%)       Q8VGW1   Olfactory receptor MOR31-7 -  Mus     1 . . . 308   253/308 (82%)   e-151             musculus  (Mouse), 312 aa.   1 . . . 308   277/308 (89%)       Q8VG78   Olfactory receptor MOR31-11 -   3 . . . 310   234/308 (75%)   e-138             Mus musculus  (Mouse), 313 aa.   1 . . . 308   265/308 (85%)                  
 
     [0468] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20F.  
               TABLE 20F                          Domain Analysis of NOV20a                                             Identities/                       Similarities for           Pfam   NOV20a Match   the Matched   Expect           Domain   Region   Region   Value                       7tm_1   43 . . . 294   49/269 (18%)   5e-15                   165/269 (61%)                       
 
     Example 21.  
     [0469] 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:99   1217 bp                     NOV21a,     GG   CCC CTGGGATCCATGCTGGCCCGGAGGAAGCCGGTGCTGCCGGCGCTCACCATCAACCCTACCA       CG55838-05       DNA Sequence   TCGCCGAGGGCCCATCCCCTACCAGCGAGGGCGCCTCCGAGGC AAA CCTGGTGGACCTGCAGAAGA                   AGCTGGAGGAGCTGGAACTTGACGAGCAGCAGAAGAAGCGCCTGGAAGCCTTTCTCACCCAGAAAG                   CCAAGGTCGGCGAACTCAAAGACGATGACTTCCAAACGATCTCAGAGCTGGGCGCGGGCAACGGCG                   GGGTGGTCACCAAAGTCCAGCACAGACCCTCGGGCCTCATCATGGCCAGGAAGCTGATCCACCTTG                   AGATCAAGCCGGCCATCCGGAACCAGATCATCCGCGAGCTGCAGGTCCTGCACGAATGCAACTCGC                   CGTACATCGTGCGCTTCTACGGGGCCTTCTACAGTGACGGCGAGATCAGCATTTGCATGCAACACA                   TGGACGGCGGCTCCCTGGACCAGGTGCTCAAAGAGGCCAAGAGGATTCCCGAGGAGATCCTGAAGA                   AAGTCAGCATCGCGGTTCTCCGGGGCTTGGCGTACCTCCGAGAGAAGCACCAGATCATGCACCGAG                   ATGTGAAGCCCTCCAACATCCTCGTGAACTCTAGAGGGGAGATCAAGCTGTGTGACTTCGGGGTGA                   GCGGCCAGCTCATAGACTCCATGGCCAACTCCTTCGTCGGCACGCGCTCCTACATAACTCCGGAGC                   GGTTGCAGGGCACACATTACTCGGTGCAGTCCGACATCTGGAGCATGGGCTTGTCCCTGGTGGAGC                   TGGCCGTCCGAAGGTACCCCATCCCCCCGCCCGACGCCAAAGAGCTGGAGGCCATCTTTGGCCGGC                   CCGTGGTCGACGGGGAAGAAGGAGAGCCTCACAGCATCTCGCCTCGGCCGAGGCCCCCCGAACGCC                   CCGTCAGCGGTCACGCGATGGATAGCCGGCCTGCCATGGCCATCTTTGAACTCCTGGACTATATTG                   TGAACGAGCCACCTCCTAAGCTGCCCAACGGTGTGTTCACCCCCGACTTCCAGGAGTTTGTCAATA                   AATGCCTCATCAAGAACCCAGCGGAGCGGGCGGACCTGAAGATGCTCACAAACCACACCTTCATCA                   AGCCGTCCGAGGTGGAAGAAGTGGATTTTGCCGGCTGGTTGTGTAAAACCCTGCGGCTGAACCAGC                   CCGGCACACCCACGCGCACCGCCGTGTGA                                         ORF Start: at 3       ORF Stop: TGA at 1215           SEQ ID NO:100   404 aa   MW at 4477.0 kD                      NOV21 a,   PLGSMLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLOKKLEELELDEQQKKRLEAFLTQKA       CG55838-05       Protein Sequence   KVGELKDDDFERISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQVLHECNSP                   YIVGFYGAFYSDGEISICMEHMDCGSLDQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHQIMHRD                   VKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMAPERLQGTHYSVQSDIWSMGLSLVEL                   AVGRYPIPPPDAKELEAIFGRPVVDGEEGEPHSISPRPRPPGRPVSGHGMDSRPAMAIFELLDYIV                   NEPPPKLPNGVFTPDFQEFVNKCLIKNPAERADLKMLTNHTFIKRSEVEEVDFAGWLCKTLRLNQP                   GTPTRTAV                                     SEQ ID NO:101   948 bp                     NOV21b,     C   ACC GGATCCACCATGCTGGCCCGGAGGAAGCCCGTGCTGCCGGCGCTCACCATCAACCCTACCAT       CG55838-05       DNA Sequence   CGCCGAGGGCCCATCCCCTACCAGCGAGGGCGCCTCCGAGGCAAACCTGGTGGACCTGCAGAAGAA                   GCTGGAGGAGCTGGAACTTGACGAGCAGCAGAAGAAGCGGCTGGAAGCCTTTCTCACCCAGAAAGC                   CAAGGTTGGCGAACTCAAACACGATGACTTCGAAAGGATCTCAGAGCTGGGCGCGGGCAACGGCGG                   GGTGGTCACCAAAGTCCAGCACACACCCTCGGGCCTCATCATGGCCAGOAAGCTGATCCACCTTGA                   GATCAAGCCGGCCATCCGGAACCAGATCATCCGCGAGCTGCAGGTCCTQCACGAATGCAACTCGCC                   GTACATCGTGGGCTTCTACGGGGCCTTCTACAGTGACGGGGAGATCAGCATTTGCATGGAACACAT                   GGACGGCGGCTCCCTGGACCAGGTGCTOAAAGAGGCCAAGAGGATTCCCGAGGAGATCCTGGGGAA                   AGTCAOCATCGCGGTTCTCCGGGGCTTGGCGTACCTCCGAGAGAAGCACCAGATCATCCACCGAGA                   TCTGAAGCCCTCCAACATCCTCGTGAACTCTAGAGGGGAGATCAACCTGTGTGACTTCGGGGTGAG                   CGGCCAGCTCATCGACTCCATGGCCAACTCCTTCGTGGCCACGCGCTCCTACATGGCTCCACCTCC                   TAAGCTGCCCAACGGTGTGTTCACCCCCCACTTCCAGGAGTTTGTCAATAAATGCCTCATCAAGAA                   CCCAGCGGAGCGGGCGGACCTGAAGATGCTCACAAACCACACCTTCATCAAGCGGTCCGAGGTGGA                   AGAAGTGGATTTTGCCGGCTGGTTGTGTAAAACCCTGCGGCTGAACCAGCCCGGCACACCCACGCG                   CACCGCCGTGTGAGCGGCCGCTAT                                         ORF Start: at 2       ORF Stop: TGA at 935           SEQ ID NO:102   311 aa   MW at 34571.5 kD                     NOV21b,   TGSTMLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQKA       CG55838-03       Protein Sequence   KVGELKDDDFERISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQVLHECNSP                   YIVGFYGAFYSDGEISICMEHMDGGSLDQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHQIMHRD                   VKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMAPPPKLPNGVFTPDFQEFVNKCLIKN                   PAERADLKMLTNHTFIKRSEVEEVDFAGWLCKTLRLNQPGTPTRTAV                                     SEQ ID NO:103   1504 bp                     NOV21c,     CCGGCCCGCGAGCCCCG   ATG CTGGCCCGGAGGAAGCCCGTGCTGCCGGCGCTCACCATCAACCCT       CG55838-02       DNA Sequence   ACCATCGCCGAGGCCCCATCCCCTACCAGCGAGGGCGCCTCCGAGGCAAACCTGGTGGACCTGCAG                   AAGAAGCTGGAGGAGCTGGAACTTGACGAGCAGCAGAAGAAGCGGCTGGAAGCCTTTCTCACCCAG                   AAAGCCAAGGTCGGCGAACTCAAAGACGATGACTTCGAAAGGATCTCAGAGCTGGGCGCGGGCAAC                   GGCGGGGTGGTCACCAAAGTCCAGCACAGACCCTCGGGCCTCATCATGGCCAGGAAGCTGATCCAC                   CTTGAGATCAAGCCGGCCATCCGGAACCAGATCATCCGCGAGCTGCAGGTCCTGCACGAATGCAAC                   TCGCCGTACATCGTGGGCTTCTACGGGGCCTTCTACAGTGACGGGGAGATCAGCATTTGCATCGAA                   CACATGGACGGCGGCTCCCTGGACCATCTCCTGAAAGAGGCCAAGAGGATTCCCGAGGAGATCCTG                   GCGAAAGTCAGCATCGCGGTTCTCCGGGGCTTGGCGTACCTCCGAGAGAAGCACCAGATCATGCAC                   CGAGATGTGAAGCCCTCCAACATCCTCGTGAACTCTAGAGGGGAGATCAAGCTGTGTGACTTCGGG                   GTGAGCGGCCAGCTCATCGACTCCATGGCCAACTCCTTCGTCGGCACGCGCTCCTACATGGCTCCG                   GAGCGGTTGCAGGGCACACATTACTCGGTGCAGTCGGACATCTGGAGCATGGGCCTGTCCCTGGTG                   GAGCTGGCCGTCGGAAGGTACCCCATCCCCCCGCCCGACGCCAAAGAGCTGGAGGCCATCTTTGGC                   CGGCCCGTGGTCGACGGGGAAGAAGGAGAGCCTCACAGCATCTCGCCTCGGCCGAGGCCCCCCGGG                   CGCCCCGTCAGCGGTCACGGGATGGATAGCCGGCCTGCCATGGCCATCTTTGAACTCCTGGACTAT                   ATTGTGAACGAGCCACCTCCTAAGCTGCCCAACGGTGTGTTCACCCCCGACTTCCAGGAGTTTGTC                   AATAAATGCCTCATCAAGAACCCAGCGGAGCGGGCGGACCTGAAGATGCTCACAAACCACACCTTC                   ATCAACCGGTCCGAGGTGGAAGAAGTGGATTTTGCCGGCTGGTTGTGTAAAACCCTGCGGCTGAAC                   CAGCCCGGCACACCCACGCGCACCGCCGTG TGA   CAGTGGCCGGGCTCCCTGCGTCCCGCTGGTGAC                       CTGCCCACCGTCCCTGTCCATGCCCCGCCCTTCCAGCTGAGCACAGGCTGGCGCCTCCACCCACCC                       TCCTGCCTCACCCCTGCGGAGAGCACCGTGGCGGGGCGACAGCGCATGCAGGAACGGGGGTCTCCT                       CTCCTGCCCGTCCTGGCCGGGGTGCCTCTGGGGACGGGCGACGCTGCTGTGTGTOGTCTCAGAGGC                       TCTGCTTCCTTAGGTTACAAAACAAAACAGGGAGAGAAAAAGCAAAAAAAAA                                           ORF Start: ATG at 19       ORF Stop: TGA at 1219           SEQ ID NO:104   400 aa   MW at 44446.7 kD                     NOV21 c,   MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQKAKVGE       CG55838-02       Protein Sequence   LKDDDFERISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVG                   FYGAFYSDGEISICMEHMDGGSLDHLLKEAKRIPEEILGKVSIAVLRGLAYLREKHQIMHRDVKPS                   NILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMAPERLQGTHYSVOSDIWSMGLSLVELAVGR                   YPIPPPDAKELEAIFGRPVVDGEEGEPHSISPRPRPPGRPVSGHGMDSRPAMAIFELLDYIVNEPP                   PKLPNGVFTPDFQEFVNKCLIKNPAERADLKMLTNHTFTKRSEVEEVDFAGWLCKTLRLNQPGTPT                   RTAV                                     SEQ ID NO:105   1227 bp                     NOV21 d,   CACCGGATCCACCATGCTCGCCCGGAGGAAGCCGGTGCTGCCGGCGCTCACCATCAACCCTACCAT       309394046 DNA       Sequence   CGCCGAGGGCCCATCCCCTACCAGCGAGGGCGCCTCCGAGCCAAACCTGGTGGACCTGCAGAAGAA                   GCTGGAGGAGCTCGAACTTGACCAGCAGCAGAAGAAGCGGCTGGAAGCCTTTCTCACCCAGAAAGC                   CAAGGTCGGCGAACTCAAAGACGATGACTTCGAAAGGATCTCAGAGCTCGGCGCGGGCAACGGCGG                   GGTGGTCACCAAAGTCCAGCACAGACCCTCGGGCCTCATCATGGCCAGGAAGCTGATCCACCTTGA                   GATCAAGCCGGCCATCCGGAACCAGATCATCCGCGAGCTGCAGGTCCTGCACGAATGCAACTCGCC                   GTACATCGTGGGCTTCTACGGGGCCTTCTACAGTGACGGGCAGATCAGCATTTGCATGGAACACAT                   GGACGGCGGCTCCCTGGACCAGGTGCTGAAAGAGGCCAAGAGGATTCCCGAGGAGATCCTGGGGAA                   AGTCAGCATCGCGGTTCTCCCGGGCTTGGCGTACCTCCGAGAGAAGCACCAGATCATGCACCGAGA                   TGTGAAGCCCTCCAACATCCTCGTGAACTCTAGAGGGGAGATCAAGCTGTGTGACTTCGGGGTGAG                   CGGCCAGCTCATCGACTCCATGGCCAACTCCTTCGTGGGCACGCGCTCCTACATGGCTCCGGAGCG                   GTTGCAGGGCACACATTACTCGGTGCAGTCGGACATCTGGAGCATGGGCCTGTCCCTGGTGGAGCT                   GGCCGTCGGAAGGTACCCCATCCCCCCGCCCGACGCCAAAGAGCTGGAGGCCATCTTTGGCCGGCC                   CGTGGTCGACGGGGAAGAAGGAGAGCCTCACAGCATCTCGCCTCGGCCGACGCCCCCCGGGCGCCC                   CGTCAGCGGTCACGGGATGGATAGCCGGCCTGCCATGGCCATCTTTGAACTCCTGGACTATATTGT                   GAACGAGCCACCTCCTAAGCTGCCCAACGGTGTGTTCACCCCCGACTTCCAGGAGTTTGTCAATAA                   ATGCCTCATCAAGAACCCAGCGGAGCOGGCGGACCTGAAGATGCTCACAAACCACACCTTCATCAA                   GCGGTCCGAGGTGGAAGAAGTGGATTTTGCCGGCTGGTTGTGTAAAACCCTGCGGCTGAACCAGCC                   CGGCACACCCACGCGCACCGCCGTG TGA   GCCGCCGCTAT                                           ORF Start: at 2       ORF Stop: TGA at 1214           SEQ ID NO:106   404 aa   MW at 44770.0 kD                     NOV21 d,   TGSTMLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQKA       309394046       Protein Sequence   KVGELKDDDREFISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQVLHECNSP                   YIVCFYGAFYSDGEISICMEHNDGGSLDQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHQIMHRD                   VKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMAPERLQGTHYSVQSDIWSMGLSLVEL                   AVGRYPIPPPDAKELEAIFGRPVVDGEEGEPHSISPRPRPPGRPVSGHGMDSRPAMAIFELLDYIV                   NEPPPKLPMGVFTPDFQEFVNKCLIKNPAERADLKMLTNHTFIKRSEVEEVDFAGWLCKTLRLMQP                   GTPTRTAV                                     SEQ ID NO:107   1164 bp                     NOV21e,     CACCGGATCCACC   ATG CTGGCCCGGAGGAAGCCGGTGCTGCCGGCGCTCACCATCAACCCTACCAT       CG55838-04       DNA Sequence   CGCCGAGGGCCCATCCCCTACCAGCGAGGGCGCCTCCGACGCAAACCTGGTGGACCTGCAGAAGAA                   GCTGGAGGAGCTGGAACTTGACGAGCAGCAGAAGAAGCGGCTGGAAGCCTTTCTCACCCAGAAAGC                   CAAGGTCGGCGAACTCAAAGACGATGACTTCGAAAGGATCTCAGAGCTGGGCGCGGGCAACGGCGG                   GGTGGTCACCAAAGTCCAGCACAGACCCTCCGGCCTCATCATGGCCAGGAAGCTGATCCACCTTGA                   GATCAAGCCCGCCATCCGGAACCAGATCATCCGCGAGCTGCAGGTCCTGCACGAATGCAACTCGCC                   GTACATCGTGGGCTTCTACGGGGCCTTCTACAGTGACGGGGACATCAGCATTTGCATCGAACACAT                   GGACGGCGGCTCCCTGGACCAGGTGCTGAAAGAGGCCAAGAGGATTCCCGAGGAGATCCTGGGGAA                   AGTCAGCATCGCGGTTCTCCGGGGCTTGGCGTACCTCCGAGAGAAGCACCAGATCATGCACCGAGA                   TGTGAAGCCCTCCAACATCCTCGTGAACTCTAGAGGGGAGATCAAGCTGTGTGACTTCGGGCCGGA                   GCGGTTGCAGCGCACACATTACTCGGTGCAGTCGGACATCTGGAGCATGGGCCTCTCCCTGGTCGA                   GCTGCCCGTCGGAAGGTACCCCATCCCCCCGCCCGACGCCAAAGAGCTGGAGGCCATCTTTGGCCG                   GCCCGTGGTCGACGGGGAAGAAGGAGAGCCTCACAGCATCTCGCCTCGGCCGAGGCCCCCCGGGCG                   CCCCGTCAGCGOTCACGGGATGGATAGCCGGCCTGCCATGGCCATCTTTGAACTCCTGGACTATAT                   TGTGAACGAGCCACCTCCTAAGCTGCCCAACGGTGTGTTCACCCCCGACTTCCAGGAGTTTGTCAA                   TAAATGCCTCATCAAGAACCCAGCGGAGCGGGCGGACCTGAAGATGCTCACAAACCACACCTTCAT                   CAAGCGGTCCGAGGTGGAAGAAGTGGATTTTGCCGGCTGGTTGTGTAAAACCCTGCGGCTGAACCA                   GCCCGGCACACCCACGCGCACCGCCGTG TGA   GCGGCCGCTAT                                           ORF Start: ATG at 14       ORF Stop: TGA at 1151           SEQ ID NO:108   379 aa   MW at 42207.1 kD                     NOV21c,   MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQKAKVGE       CG55838-04       Protein Sequence   LKDDDFERISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVG                   FYGAFYSDGEISICMEHMDGGSLDQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHQIMHRDVKPS                   NILVNSRGEIKLCDFGPERLQGTHYSVQSDIWSMGLSLVELAVGRYPIPPPDAKELEAIFGRPVVD                   GEEGEPHSISPRPRPPGRPVSGHGMDSRPAMAIFELLDYIVNEPPPKLPNGVFTPDFQEFVNKCLI                   KISTPAERADLKMLTNHTFIKRSEVEEVDFAGWLCKTLRLNQPGTPTRTAV                                     SEQ ID NO:109   985 bp                     NOV21f     TCCACTACGGGCCCAGGCTAGAGGCGCCGCCGCCGCCGGCCCGCGGAGCCCCG   ATG CTGGCCCGGA       CG55838-01       DNA Sequence   GGAAGCCGGTGCTGCCGGCGCTCACCATCAACCCTACCATCGCCGAGGGCCCATCCCCTACCAGCG                   AGCGCGCCTCCGAGGCAAACCTGGTGGACCTGCAGAAGAAGCTGGAGGAGCTGGAACTTGACGAGC                   AGCAGAAGAAGCGGCTGGAAGCCTTTCTCACCCAGAAAGCCAAGGTCGGCGAACTCAAAGACGATG                   ACTTCGAAAGGATCTCAGAGCTGGGCGCCGGCAACGGCGGGGTGGTCACCAAAGTCCAGCACAGAC                   CCTCGGGCCTCATCATGGCCAGGAAGCTGATCCACCTTGAGATCAAGCCGGCCATCCGGAACCAGA                   TCATCCGCGAGCTGCAGGTCCTGCACGAATGCAACTCGCCGTACATCGTGGGCTTCTACGGGGCCT                   TCTACAGTGACGGGGAGATCAGCATTTGCATGGAACACATGGACGGCGGCTCCCTCGACCAGGTGC                   TGAAAGAGGCCAAGAGGATTCCCGAGGAGATCCTGGGGAAAGTCAGCATCGCGGTTCTCCGGGGCT                   TGGCGTACCTCCGAGAGAAGCACCAGATCATGCACCGAGATGTGAAGCCCTCCAACATCCTCGTGA                   ACTCTAGAGGGGAGATCAAGCTGTGTGACTTCGGGGTGAGCGGCCAGCTCATCGACTCCATGGCCA                   ACTCCTTCGTGGGCACGCGCTCCTACATGGCTCCACCTCCTAAGCTCCCCAACGGTGTGTTCACCC                   CCGACTTCCAGGACTTTGTCAATAAATGCCTCATCAAGAACCCAGCGGAGCGGGCGGACCTGAAGA                   TGCTCACAAACCACACCTTCATCAAGCGGTCCGAGGTGGAAGAAGTGGATTTTGCCCGCTAATTGT                   GTAAAACCCTGCGGCTGAACCAGCCCGGCACACCCACGCGCACCCCCGTGTACAGTGGC AA                                           ORF Start: ATG at 54       ORF Stop: at 984           SEQ ID NO:110   310 aa   MW at 34532.5 kD                     NOV21F,   MLARRKPVLPALTINPTTAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQKAKVGE       CG55838-01       Protein Sequence   LKDDDFERISELGAGNGGVVTKVQHRPSGLIMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVG                   FYGAFYSDGEISICMEHMDGGSLDQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHQIMHRDVKPS                   NILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMAPPPKLPNGVFTPDFQEFVNKCLIKNPAER                   ADLKMLTNHTFIKRSEVEEVDFAGWLCKTLRLNQPGTPTRTAVYSG                                     SEQ ID NO:111   1161 bp                     NOV21g,     CACCGGATCC   ATG CTGGCCCGGAGGAAGCCGGTGCTGCCGGCGCTCACCATCAACCCTACCATCGC       CG55838-06       DNA Sequence   CGAGGGCCCATCCCCTACCAGCGAGGGCGCCTCCGAGGCAAACCTGGTGGACCTGCAGAAGAAGCT                   GGAGGAGCTGGAACTTGACGAGCAGCAGAAGAAGCGGCTGGAAGCCTTTCTCACCCAGAAAGCCAA                   GGTCGGCGAACTCAAAGACGATGACTTCGAAAGGATCTCAGAGCTGGGCGCGGGCAACGGCGGGGT                   GGTCACCAAAGTCCAGCACAGACCCTCGCGCCTCATCATGGCCAGGAAGCTGATCCACCTTGAGAT                   CAAGCCGGCCATCCGGAACCAGATCATCCGCGAGCTGCAGGTCCTGCACGAATGCAACTCGCCGTA                   CATCGTGGGCTTCTACGGGGCCTTCTACAGTGACGGGGAGATCAGCATTTGCATGGAACACATGGA                   CGGCGGCTCCCTGGACCAGGTGCTGAAAGAGGCCAAGAGGATTCCCGAGGAGATCCTGGGGAAAGT                   CAGCATCGCGGTTCTCCGGGGCTTGGCGTACCTCCGAGAGAAGCACCAGATCATGCACCGAGATGT                   GAAGCCCTCCAACATCCTCGTGAACTCTAGAGGGGAGATCAAGCTGTGTGACTTCGGGCCGGAGCG                   GTTGCAGGGCACACATTACTCGGTGCAGTCGGACATCTGGAGCATGGGCCTGTCCCTGGTAAAGCT                   GGCCGTCGGAAGGTACCCCATCCCCCCGCCCGACGCCAAAGAGCTGGAGGCCATCTTTGGCCGGCC                   CGTGGTCGACGGGGAAGAAGGAGAGCCTCACAGCATCTCGCCTCGGCCGAGGCCCCCCGGGCGCCC                   CGTCAGCGGTCACGCGATGGATAGCCGGCCTGCCATGGCCATCTTTGAACTCCTGGACTATATTGT                   GAACGAGCCACCTCCTAAGCTGCCCAACGGTGTGTTCACCCCCGACTTCCAGGAGTTTGTCAATAA                   ATGCCTCATCAAGAACCCAGCGGAGCGGGCGGACCTGAAGATGCTCACAAACCACACCTTCATCAA                   GCGGTCCGAGGTGGAAGAAGTGGATTTTGCCGGCTGGTTGTGTAAAACCCTGCGGCTGAACCAGCC                   CGGCACACCCACGCGCACCGCCGTG TGA   GCGGCCGCAAG                                           ORF Start: ATG at 11       ORF Stop: TGA at 1148           SEQ ID NO:112   379 aa   MW at 42207.1 kD                     NOV21g,   MLARRKPVLPALTINPTIAEGPSPTSEGASEANLVDLQKKLEELELDEQQKKRLEAFLTQKAKVGE       CG55838-06       Protein Sequence   LKDDDFERISELGAGNGGVVTKVQHRPSGLIMARKLTHLEIKPAIRNQIIRELQVLHECNSPYIVG                   FYGAFYSDGEISICMEHMDGGSLDQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHQIMHRDVKPS                   NILVNSRGEIKLCDFGPERLQGTHYSVQSDIWSMGLSLVELAVGRYPIPPPDAAALEAIFGRPVVD                   GEEGEPHSISPRPRPPGRPVSGHGMDSRPAMAIFELLDYIVNEPPPKLPNGVFTPDFQEFVNKCLI                   KNPAERADLKMLTNHTFIKRSEVEEVDFAGWLCKTLRLNQPGTPTRTAV                  
 
     [0470] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 211B.  
               TABLE 21B                          Comparison of NOV21a against NOV21b through NOV21g.                                         Identities/                   Similarities for           Protein   NOV21a Residues/   the Matched           Sequence   Match Residues   Region                       NOV21b   4 . . . 240   236/237 (99%)               4 . . . 240   237/237 (99%)           NOV21c   5 . . . 404   398/400 (99%)               1 . . . 400   399/400 (99%)           NOV21d   4 . . . 404   400/401 (99%)               4 . . . 404   401/401 (99%)           NOV21e   5 . . . 404   379/400 (94%)               1 . . . 379   379/400 (94%)           NOV21f   5 . . . 240    236/236 (100%)               1 . . . 236    236/236 (100%)           NOV21g   5 . . . 404   379/400 (94%)               1 . . . 379   379/400 (94%)                      
 
     [0471] Further analysis of the NOV21 a protein yielded the following properties shown in Table 21C.  
               TABLE 21C                       Protein Sequence Properties NOV21a                                        SignalP   No Known Signal Sequence Predicted       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 10; pos. chg 3; neg. chg 0           H-region: length 13; peak value 7.17           PSG score: 2.77           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −5.47           possible cleavage site: between 23 and 24           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 2.92 (at 172)           ALOM score: 2.92 (number of TMSs: 0)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 6           Charge difference: 2.0 C(3.0)-N(1.0)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt;Caution: Inconsistent mtop result with signal peptide           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   2   Hyd Moment (75):   8.14           Hyd Moment (95):   8.83   G content:   1           D/E content:   1   S/T content:   3                         Score: −2.14           Gavel: prediction of cleavage sites for mitochondrial preseq           R-2 motif at 19 RRK|PV           NUCDISC: discrimination of nuclear localization signals           pat4: RRKP (4) at 8           pat7: none           bipartite: KKLEELELDEQQKKRLE at 43           content of basic residues: 12.1%           NLS Score: 0.27           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: found           KLPN at 336           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 70.6           COIL: Lupas&#39;s algorithm to detect coiled-coil regions                                     28 T   0.63                   29 S   0.80           30 E   0.80           31 G   0.80           32 A   0.95           33 S   0.95           34 E   0.99           35 A   0.99           36 N   0.99           37 L   0.99           38 V   0.99           39 D   0.99           40 L   0.99           41 Q   0.99           42 K   0.99           43 K   0.99           44 L   0.99           45 E   0.99           46 E   0.99           47 L   0.99           48 E   0.99           49 L   0.99           50 D   0.99           51 E   0.99           52 Q   0.99           53 Q   0.99           54 K   0.99           55 K   0.99           56 R   0.99           57 L   0.99           58 E   0.99           59 A   0.99           60 F   0.99           61 L   0.99           62 T   0.98           63 Q   0.98           64 K   0.98           65 A   0.98           66 K   0.98           67 V   0.85                         total: 40 residues           Final Results (k = 9/23):           43.5%: mitochondrial           34.8%: nuclear           17.4%: cytoplasmic            4.3%: vacuolar           &gt;&gt; prediction for CG55838-05 is mit (k = 23)                  
 
     [0472] A search of the NOV21 a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 21D.  
               TABLE 21D                          Geneseq Results for NOV21a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV21a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value                                         AAY41652   Human MEK2 protein sequence -   5 . . . 404    400/400 (100%)   0.0             Homo sapiens , 400 aa.   1 . . . 400    400/400 (100%)           [US5959097-A, 28 SEP. 1999]       AAM38714   Human polypeptide SEQ ID NO   5 . . . 404   399/400 (99%)   0.0           1859 -  Homo sapiens , 400 aa.   1 . . . 400   399/400 (99%)           [WO200153312-A1, 26 JUL. 2001]       AAW88434   Disease associated protein kinase   5 . . . 404   398/400 (99%)   0.0           DAPK-3 -  Homo sapiens , 400 aa.   1 . . . 400   399/400 (99%)           [WO9858052-A2, 23 DEC. 1998]       AAM40501   Human polypeptide SEQ ID NO   7 . . . 404   395/398 (99%)   0.0           5432 -  Homo sapiens , 435 aa.   38 . . . 435    396/398 (99%)           [WO200153312-A1, 26 JUL. 2001]       AAM40500   Human polypeptide SEQ ID NO   7 . . . 404   395/398 (99%)   0.0           5431 -  Homo sapiens , 435 aa.   38 . . . 435    396/398 (99%)           [WO200153312-A1, 26 JUL. 2001]                  
 
     [0473] In a BLAST search of public sequence databases, the NOV21 a protein was found to have homology to the proteins shown in the BLASTP data in Table 21E.  
               TABLE 21E                          Public BLASTP Results for NOV21a                                             Identities/           Protein           Similarities for       Accession       NOV21a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value                                         P36507   Dual specificity mitogen-activated   5 . . . 404    400/400 (100%)   0.0           protein kinase kinase 2 (EC 2.7.1.-)   1 . . . 400    400/400 (100%)           (MAP kinase kinase 2) (MAPKK 2)           (ERK activator kinase 2) (MAPK/ERK           kinase 2) (MEK2) -  Homo sapiens             (Human), 400 aa.       Q91YS7   Hypothetical 44.3 kDa protein -  Mus     5 . . . 404   377/400 (94%)   0.0             musculus  (Mouse), 400 aa.   1 . . . 400   391/400 (97%)       P36506   Dual specificity mitogen-activated   5 . . . 404   376/400 (94%)   0.0           protein kinase kinase 2 (EC 2.7.1.-)   1 . . . 400   392/400 (98%)           (MAP kinase kinase 2) (MAPKK 2)           (ERK activator kinase 2) (MAPK/ERK           kinase 2) (MEK2) -  Rattus norvegicus             (Rat), 400 aa.       Q9D7B0   Mitogen activated protein kinase kinase   5 . . . 404   377/401 (94%)   0.0           2 -  Mus musculus  (Mouse), 401 aa.   1 . . . 401   391/401 (97%)       Q63932   Dual specificity mitogen-activated   5 . . . 404   376/401 (93%)   0.0           protein kinase kinase 2 (EC 2.7.1.-)   1 . . . 401   390/401 (96%)           (MAP kinase kinase 2) (MAPKK 2)           (ERK activator kinase 2) (MAPK/ERK           kinase 2) (MEK2) -  Mus musculus             (Mouse), 401 aa.                  
 
     [0474] PFam analysis predicts that the NOV21 a protein contains the domains shown in the Table 21F.  
               TABLE 21F                          Domain Analysis of NOV21a                                             Identities/                       Similarities for           Pfam   NOV21a Match   the Matched   Expect           Domain   Region   Region   Value                       pkinase   76 . . . 373   88/314 (28%)   4.9e−72                   231/314 (74%)                       
 
     Example 22.  
     [0475] 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:113   2246 bp                     NOV22a,     CCTGAGGAAGTGCACCATGGAGAGGAGGAGGTGGAGACTTTTGCCTTTCAGGCAGAAATTGCCCAA         CG56618-02       DNA Sequence   CTCATGTCCCTCATCATCAATACCTTCTATTCCAACAAGGAGATTTTCCTTCGGGAGTTGATCTCT                   AATGCTTCTGATGCCTTGGACAAGATTCGCTATGAGAGCCTGACAGACCCTTCGAAGTTGGACAGT                   GGTAAAGAGCTGAAAATTGACATCATCCTCAACCCTCAGGAACGTACCCTGACTTTGGTAGACACA                   GGCATTGGCATGACCAAAGCTGATCTCATAAATAATTTGGGAACCATTGCCAAGTCTGGTACTAAA                   GCATTCATGGAGGCTCTTCAGGCTGGTGCAGACATCTCCATGATTGGGCAGTTTGGTGTTGGCTTT                   TATTCTGCCTACTTGGTGGCAGAGAAAGTGGTTGTGATCACAAAGCACAACGATGATGAACAGTAT                   GCTTGGGAGTCTTCTGCTGGAGGTTCCTTCACTGTGCGTGCTGACCATGGTGAGCCCATTGGCAGG                   GGTACCAAAGTGATCCTCCATCTTAAAGAAGATCAGACAGAGTACCTAGAAGAGAGGCGGGTCAAA                   GAAGTAGTGAAGAAGCATTCTCAGTTCATAGGCTATCCCATCACCCTTTATTTGGAGAAGGAACGA                   GAGAAGGAAATTAGTGATGATGAGGCAGAGGAAGAGAAAGGTGAGAAAGAAGAGGAAGATAAAGAT                   GATGAAGAAAAGCCCAAGATCGAAGATGTGGGTTCAGATGAGGAGGATGACAGCGGTAAGGATAAG                   GAGAAGAAAACTAAGAAGATCAAAGAGAAATACATTGATCAGGAAGAACTAAACAAGACCAAGCCT                   ATTTGGACCAGAAACCCTGATGACATCACCCAAGAGGAGTATGGAGAATTCTACAAGAGCCTCACT                   AATGACTGGGAAGACCACTTGGCAGTCAAGCACTTTTCTGTAGAAGGTCAGTTGGAATTCAGGGCA                   TTGCTATTTATTCCTCGTCGGGCTCCCTTTGACCTTTTTGAGAACAAGAAGAAAAAGAACAACATC                   AAACTCTATGTCCGCCGTGTGTTCATCATGGACAGCTGTGATGAGTTGATACCAGAGTATCTCAAT                   TTTATCCGTGGTGTGGTTGACTCTGAGGATCTGCCCCTGAACATCTCCCGAGAAATGCTCCAGCAG                   AGCAAAATCTTGAAAGTCATTCGCAAAAACATTGTTAAGAACTGCCTTGAGCTCTTCTCTGAGCTG                   GCAGAAGACAAGGAGAATTACAAGAAATTCTATGAGGCATTCTCTAAAAATCTCAAGCTTGGAATC                   CACGAACACTCCACTAACCGCCGCCGCCTGTCTGAGCTGCTGCGCTATCATACCTCCCAGTCTGGA                   GATGAGATGACATCTCTGTCAGAGTATGTTTCTCGCATCAAGGAGACACAGAAGTCCATCTATTAC                   ATCACTGGTGAGAGCAAAGAGCAGGTGGCCAACTCAGCTTTTGTGGAGCGAGTGCGGAAACGGGGC                   TTCGAGGTGGTATATATGACCGAGCCCATTGACGAGTACTGTGTGCAGCAGCTCAAGGAATTTGAT                   GGGAAGAGCCTGGTCTCAGTTACCAAGGAGGGTCTGGAGCTGCCTGAGGATGAGGAGGAGAAGAAG                   AAGATGGAAGAGAGCAAGGCAAAGTTTGAGAACCTCTGCAAGCTCATGAAAGAAATCTTAGATAAG                   AAGGTTGAGAAGGTGACAATCTCCAATAGACTTGTGTCTTCACCTTGCTGCATTGTGACCAGCACC                   TACGGCTGGACAGCCAATATGGAGCGGATCATGAAAGCCCAGGCACTTCGGGACAACTCCACCATG                   GGCTATATGATGGCCAAAAACCACCTGGAGATCAACCCTGACCACCCCATTGTAAAGACGCTGCGG                   CAGAAGGCTGAGGCCGACAAGAATGATAAGGCAGTTAAGGACCTGGTGGTGCTGCTGTTTGAAACC                   GCCCTGCTATCTTCTGGCTTTTCCCTTGAGGATCCCCAGACCCACTCCAACCGCATCTATCCCATG                   ATCAAGCTAGGTCTAGGTATTGATGAAGATGAAGTGGCAGCAGAGGAACCCAATGCTGCAGTTCCT                   GATGAGATCCCCCCTCTCGAGGGCGATGAGGATGCGTCTCGCATGGAAGAAGTCGAT TAG   TTAGG                       AGTTCATAGTTGGAAAACTTGTGCCCTTGTATAGTGTCCCCATaaGCTCCCACAGTACTTGTTAGC                       TA                                           ORF Start: at 1       ORF Stop: TAG at 2170           SEQ ID NO:114   723 aa   MW at 83149.1 kD                     NOV22a,   PEEVHHGEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNASDALDKIRYESLTDPSKLDS       CG56618-02       Protein Sequence   GKELKIDIILNPQERTLTLVDTGIGMTKADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVGF                   YSAYLVAEKVVVITKHNDDEQYAWESSAGGSFTVRADHGEPIGRGTKVILHLKEDQTEYLEERRVK                   EVVKKHSQFIGYPITLYLEKEREKEISDDEAEEEKGEKEEEDKDDEEKPKIEDVGSDEEDDSGKDK                   EKKTKKIKEKYIDQEELNKTKPIWTRNPDDITQEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRA                   LLFIPRRAPFDLFENKKKKNNIKLYVRRVFIMDSCDELIPEYLNFIRGVVDSEDLPLNISREMLQQ                   SKILKVIRKNIVKKCLELFSELAEDKENYKKFYEAFSKNLKLGIHEDSTNRRRLSELLRYHTSQSG                   DEMTSLSEYVSRMKETQKSIYYITGESKEQVANSAFVERVRKRGFEVVYMTEPIDEYCVQQLKEFD                   GKSLVSVTKEGLELPEDEEEKKKMEESKAKFENLCKLMKEILDKKVEKVTISNRLVSSPCCIVTST                   YGWTANMERIMKAQALRDNSTMGYMMAKKHLEINPDHPIVETLRQKAEADKNDKAVKDLVVLLFET                   ALLSSGFSLEDPQTHSNRIYRMIKLGLGIDEDEVAAEEPNAAVPDEIPPLEGDEDASRMEEVD                                     SEQ ID NO:115   1365 bp                     NOV22b,     GGCACGAGGCTCCGGCGCAGTGTTGGGACTGTCTGGGTATCGGAAAGCAAGCCTACGTTGCTCACT         CG56618-03       DNA Sequence     ATTACGTATAATCCTTTTCTTTTCAAG   ATG CCTGAGGAAGTGCACCATGGAGAGGAGGAGGTGGAG                   ACTTTTGCCTTTCAGGCAGAATTGCCCAACTCATGTCCCTCATCATCAATACCTTCTATTCCAAAC                   AAGGAGATTTTCCTTCGGGAGTTGATCTCTAATGCTTCTGATGCCTTGGACAAGATTCGCTATGAC                   AGCCTGACAGACCCTTCGAAGTTGGACAGTGGTAAAGAGCTGAAAATTGACATCATCCCCAACCCT                   CAGGAACGTACCCTGACTTTGGTAGACACAGGCATTGGCATGACCAAAGCTGATCTCATAAATAAT                   TTGGGAACCATTGCCAAGTCTGGTACTAAAGCATTCATGGAGGCTCTTCAGATGAGGAGGATGACA                   GCGGTAAGGATAAGAAGAAGAAAACTAAGAAGATCAAAGAGAAATACATTGATCAGGAAGATGGAA                   GAGAGCAGGCAAAGTTTGAGAACCTCTGCAAGCTCATGAAAGAAATCTTAGATAAGAAAGGTTGAG                   AAGGTGACAATCTCCAATAGACTTGTGTCTTCACCTTGCTGCATTGTGACCAGCACCTACGGCTAA                   ACAGCCAATATGGAGCGGATCATGAAAGCCCAGGCACTTCGGGACAACTCCACCATGGGCTATATG                   ATGGCCAAAAAGCACCTCGAGATCAACCCTGACCACCCCATTGTGGAGACGCTGCAGAAGGCTTTG                   GAGGCCGACAAGAATGATAAGGCAGTTAAGGACCTGGTGGTGCTGCTGTTTGAAACCGCCCTGCTA                   TCTTCTGGCTTTTCCCTTGAGGATCCCCAGACCCATCTCCAACCGCATCTATCGCATGATCAAGCTA                   GGTCTAGGTATTGATGAAGATGAAGTGGCAGCAGAGGAACCCAATGCTGCAGTTCCTGATGAGATC                   CCCCCTCTCGAGGGCGATGAGGATGCGTCTCGCATGGAAGAAGTCGAT TAG   GTTAGGAGTTCATAG                       TTGGAAAACTTGTGCCCTTGTATAGTGTCCCCATGGGCTCCCACTGCAGCCTCGAGTGCCCCTGTC                       CCACCTCGCTCCCCCTGCTCGTGTCTAGTGTTTTTTTCCCTCTCCTGTCCTTGTGTTGAAGGCAGT                       AAACTAAGGGTGTCAAGCCCCATTCCCTCTCTACTCTTCACAGCAGGATTGGATGTTGTGTATTGT                       GGTTTATTTTATTTTCTTCATTTTGTTCTGAAATTAAAGTATGCAAAATAAAGAATATGCCGTTTT                       TATAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA                                           ORF Start: ATG at 94       ORF Stop: TAG at 1039           SEQ ID NO:116   315 aa   MW at 35744.6 kD                     NOV22b,   MPEEVHHGEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNASDALDKIRYESLTDPSKLD       CG56618-03       Protein Sequence   SGKELKIDIIPNPQERTLTLVDTGIGMTKADLINNLGTIAKSGTKAFMEALQMRRMTAVRIRRRKL                   RRSKRNTLIRKMEESRAKFENLCKLMKEILDKKVEKVTISNRLVSSPCCIVTSTYGWTANMERIMK                   AQALRDNSTMGYMMAKKHLEINPDHPIVETLRQKAEADKNDKAVKDLVVLLFETALLSSGFSLEDP                   QTHSNRIYRMIKLGLGIDEDEVAAEEPNAAVPDEIPPLEGDEDASRMEEVD                   QTHSKRIYRMIKLGLGIDEDEVAAEEPNAAVPDEIPPLEGDEDASRMEEVD                                     SEQ ID NO:117   2564 bp                     NOV22c,     GGCACGAGGCTCCGGCCCAGTGTTGGGACTGTCTGGGTATCGGAAAGCAAGCCTACGTTGCTCACT         CG56618-04       DNA Sequence     ATTACGTATAATCCTTTTCTTTTCAAG   ATG CCTGAGGAAGTGCACCATGGAGAGGAGGAGGTGGAG                   ACTTTTGCCTTTCAGGCAGAAATTGCCCAACTCATGTCCCTCATCATCAATACCTTCTATTCCAAC                   AAGGAGATTTTCCTTCGGGAGTTGATCTCTAATGCTTCTGATGCCTTGGACAAGATTCGCTATGAG                   AGCCTGACAGACCCTTCGAAGTTGGACAGTGGTAAAGAGCTGAAAATTGACATCATCCCCAACCCT                   CAGGAACGTACCCTGACTTTGGTAGACACAGGCATTGGCATGACCAAAGCTGATCTCATAAATAAT                   TTGGGAACCATTGCCAAGTCTGGTACTAAAGCATTCATGGAGGCTCTTCAGGCTGGTGCAGACATC                   TCCATCATTGGGCAGTTTGGTGTTGGCTTTTATTCTGCCTACTTGGTACAGAGAAGAGTGGTTGTG                   ATCACAAAGCACAACGATGATGAACAGTATGCTTGGGAGTCTTCTGCTGGAGGTTCCTTCACTGTG                   CGTGCTGACCATGGTGAGCCCATTGGCAGGGGTACCAAAGTGATCCTCCATCTTAAAGAAGATCAG                   ACAGAGTACCTAGAAGAGAGGCGGGTCAAAGAAGTAGTGGGAAGCCATTCTCAGTTCATAGGCTAT                   CCCATCACCCTTTATTTGGAGAAGGAACGAGAGAAGGAAATTAGTGATGATGAGGCAGAGGAAGAG                   AAAGGTGAGAAAGAAGAGGAAGATAAAGATGATGAAGAAAAACCCAAGATCGAAGATGTGGGTTCA                   GATGAGGAGGATGACAGCGGTAAGGATAAGAAGAAGAAAACTAAGAAGATCAAAGAGAAATACATT                   GATCAGGAAGAACTAAACAAGACCAAGCCTATTTGGACCAGAAACCCTGATGACATCACCCAAGAG                   GAGTATGGAGAATTCTACAAGAGCCTCACTAATGACTGGGAAGACCACTTGGCAGTCAAGCACTTT                   TCTGTAGAAGGTCACTTGGAATTCAGGGCATTGCTATTTATTCCTCGTCGGGCTCCCTTTGACCTT                   TTTCAGAACAAGAAGAAAAAGAACAACATCAAACTCTATGTCCGCCGTGTGTTCATCATGGACACC                   TGTGATGAGTTGATACCAGAGTATCTCAATTTTATCCGTGGTGTGGTTGACTCTGAGGATCTGCCC                   CTGAACATCTCCCGAGAAATGCTCCAGCAGAGCAAAATCTTGAAAGTCATTCGCAAAAACATTGTT                   AGAAGTGCCTTGAGCTCTTCTCTGAGCTGGCAGAAGACAAGGAGAATTACAAGAAAATTCTATGAG                   GCATTCTCTAAAAATCTCAAGCTTGGAATCCACGAAGACTCCACTAACCCCCGCCGCCTGTCTGAG                   CTGCTGCGCTATCATACCTCCCAGTCTGCAGATGAGATGACATCTCTGTCAGAGTATGTTTCTCGC                   ATGAAGGAGACACAGAAGTCCATCTATTACATCACTGGTGAGAGCAAAGAGCAGGTGGCCAACTCA                   GCTTTTGTGGAGCGAGTGCGGAAACGGGGCTTCGAGGTGGTATATATGACCGAGCCCATTGACGAG                   TACTGTGTGCAGCAGCTCAAGGAATTTGATGGGAAGAGCCTCGTCTCAGTTACCAAGGAGGGTCTG                   GAGCTGCCTGAGGATGAGGAGGAGAAGAAGAAGATGGAAGAGAGCAAGGCAAAGTTTGAGAACCTC                   TGCAAGCTCATGAAAGAAATCTTAGATAAGAAGGTTGAGAAGGTGACAATCTCCAATAGACTTGTG                   TCTTCACCTTGCTGCATTGTGACCAGCACCTACGGCTGGACAGCCAATATGGAGCGGATCATGAAA                   GCCCAGGCACTTCGGGACAACTCCACCATGGGCTATATGATGGCCACCCCATTGTGGAGACGCTGC                   GGCAGAAGGCTGAGGCCGACAAGAATGATAAGGCAGTTAAGGACCTGGTGGTGCTGCTGTTTGAAA                   CCGCCCTGCTATCTTCTGGCTTTTCCCTTGAGCATCCCCAGACCCACTCCAACCGCATCTATCGCA                     TGA   TCAAGCTAGGTCTAGGTATTGATGAAGATGAAGTGGCAGCAGAGGAACCCAATGCTGCAGTTC                       CTGATGAGATCCCCCCTCTCGAGGGCGATGAGGATGCGTCTCGCATGGAAGAAGTCGATTAGGTTA                       GGAGTTCATAGTTGGAAAACTTGTGCCCTTGTATAGTGTCCCCATGGGCTCCCACTGCAGCCTCGA                       GTGCCCCTGTCCCACCTGGCTCCCCCTGCTCGTGTCTAGTGTTTTTTTCCCTCTCCTGTCCTTGTG                       TTGAAGGCAGTAAACTAAGGGTGTCAAGCCCCATTCCCTCTCTACTCTTGACACCAGGATTGGATG                       TTGTGTATTGTGGTTTATTTTATTTTCTTCATTTTGTTCTGAAATTAAAGTATGCAAAATAAAGAA                       TATGCCGTTTTTATAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA                                           ORF Start: ATG at 94       ORF Stop: TGA at 2113           SEQ ID NO:118   673 aa   MW at 78025.1 kD                     NOV22c,   MPEEVHHGEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNASDALDKIRYESLTDPSKLD       CG56618-04       Protein Sequence   SGKELKIDIIPNPQERTLTLVDTGIGMTKADLINNLGTTAKSGTKAFMEALQAGADISMIGQFGVG                   FYSAYLVAEKVVVITKHNDDEQYAWESSAGGSFTVRADHGEPIGRGTKVILHLKEDQTEYLEERRV                   KEVVKKHSQFIGYPITLYLEKEREKEISDDEAEEKGEKEEEKDKKEEKPKIEDSVGSDEEDDSGKD                   KKKKTKKIKEKYIDQEELNKTKPIWTRNPDDITQEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFR                   ALLFIPRRAPFDLFENKKKKNNIKLYVRRVFIMDSCDELIPEYLNFIRGVVDSEDLPLNISREMLQ                   QSKILKVIRKNIVKKCLELFSELAEDKENYKKFYEAFSKNLKLGIHEDSTNRRRLSELLRYHTSQS                   GDEMTSLSEYVSRMKETQKSIYYITGESKEQVANSAFVERVRKRGFEVVYMTEPIDEYCVQQLKEF                   DGKSLVSVTKEGLELPEDEEEKKKMEESKAKFENLCKLMKEILDKKVEKVTISNRLVSSPCCIVTS                   TYGWTANMERIMKAQALRDNSTMGYMMATPLWRRCGRRLRPTRMIRQLRTWWCCCLKPPCYLLAFP                   LRIPRPTPTASIA                                     SEQ ID NO:119   2540 bp                     NOV22d,     CTCCCGCGCAGTGTTGGGACTGTCTGGGTATCGGAAAGCAAGCCTACGTTGCTCACTATTACGTAT         CG56618-01       DNA Sequence     AATCCTTTTCTTTTCAAG   ATG CCTGAGGAAGTGCACCATCGAGAGGAGGAGGTGGAGACTTTTGCC                   TTTCAGGCAGAAATTGCCCAACTCATGTCCCTCATCATCAATACCTTCTATTCCAACAAGGAGATT                   TTCCTTCGGGAGTTGATCTCTAATGCTTCTGATGCCTTGGACAAGATTCGCTATGAGAGCCTGACA                   GACCCTTCGAAGTTGGACAGTGGThAAGAGCTGAAAATTGACATCATCCCCAACCCTCAGGAACGT                   ACCCTGACTTTGGTAGACACAGGCATTGGCATGACCAAAGCTGATCTCATAAATAATTTGGGAACC                   ATTGCCAAGTCTGGTACTAAAGCATTCATGGAGGCTCTTCAGGCTGGTGCAGACATCTCCATGATT                   GGGCAGTTTGOTGTTGGCTTTTATTCTGCCTACTTGGTCGCAGAGAAAGTGGTTGTGATCAGAAAG                   CACAACGATGATGAACAGTATGCTTGGGAGTCTTCTGCTGGAGGTTCCTTCACTGTGCGTGCTGAC                   CATGGTGAGCCCATTGGCATGGGTACCAAAGTGATCCTCCATCTTAAAGAAGATCAGACAGAGTAC                   CTAGAAGAGAGGCGGGTCAAAGAAGTAGTGAAGAAGCATTCTCAGTTCATAGGCTATCCCATCACC                   CTTTATTTGGAGAAGGAACGAGAGAAGGAAATTAGTGATGATGAGGCAGAGCAAGAGAAAGGTGAG                   AAAGAAGACGAAGATAAAGATGATGAAGAAAAGCCCAAGATCGAAGATGTGGGTTCAGATGAGGAG                   GATGACAGCGGTAAGGATAAGAAGAAGAAAACTAAGAAGATCAAAGAGAAATACATTGATCAGGAA                   GAACTAAACAAGACCAAGCCTATTTGGACCAGAAACCCTGATGACATCACCCAAGAGGAGTATGGA                   GAATTCTACAAGAGCCTCACTAATGACTGGGAAGACCACTTGGCAGTCAAGCACTTTTCTGTAGAA                   GGTCAGTTGAATTCAGGCCATTGCTATTTATTCCTCGTCGGGCTCCCTTTGACCTTTTTGAGAAAC                   AAGAAGAAAAAGAACAACATCAAACTCTATGTCCGCCGTGTGTTCATCATGGACAGCTGTGATGAG                   TTGATACCAGAGTATCTCAATTTTATCCGTCGTGTGGTTGACTCTGAGGATCTGCCCCTGAACATC                   TCCCGAGAAATGCTCCAGCAGAGCAAAATCTTGAAAGTCATTCGCAAAAACATTGTTAAGAAGTGC                   CTTGAGCTCTTCTCTGAGCTCGCACAAGACAAGGAGAATTACAAGAAATTCTATGAGGCATTCTCT                   AAAAATCTCAAGCTTGGAATCCACGAAGACTCCACTAACCGCCGCCGCCTGTCTGAGCTGCTGCGC                   TATCATACCTCCCAGTCTGGAGATGAGATGACATCTCTGTCAGAGTATGTTTCTCGCATGAAGGAG                   ACACAGAAGTCCATCTATTACATCACTGGTGAGAGCAAGAGCAGGTGGCCAACTCAGCTTTTGGTG                   GAGCGAGTGCGGAAACGGGGCTTCGAGGTGGTATATATGACCGAGCCCATTGACGAGTACTGTGTG                   CAGCAGCTCAAGGAATTTGATGGGAAGAGCCTGGTCTCAGTTACCAAGGAGGGTCTGGAGCTGCCT                   GAGGATGAGGAGGAGAAGAAGAAGATGGAAGAGAGCAAGGCAAAGTTTGAGAACCTCTGCAAGCTC                   ATGAAACAAATCTTAGATAAGAAGGTTGAGAAGGTGACAATCTCCAATAGACTTGTGTCTTCACCT                   TGCTGCATTGTGACCAGCACCTACGGCTGGACAGCCAATATGGAGCGGATCATGAAAGCCCAGGCA                   CTTCGGGACAACTCCACCATGGGCTATATGATGGCCAAAAAGCACCTGGAGATCAACCCTGACCAC                   CCCATTGTGGAGACGCTGCGGCAGAAGGCTGAGGCCGACAGAATGATAAGGCAGTTAAGCGACCTG                   GTGGTGCTGCTGTTTGAAACCGCCCTGCTATCTTCTGGCTTTTCCCTTGAGGATCCCCAGACCCAC                   TCCAACCGCATCTATCGCATGATCAAGCTAGGTCTAGGTATTGATGAAGATGAAGTGGCAGCAGAG                   GAACCCAATGCTGCAGTTCCTGATGAGATCCCCCCTCTCGAGCGCGATGAGGATGCGTCTCGCATG                   GAAGAAGTCGAT TAG   GTTAGGAGTTCATAGTTGGAAAACTTGTGCCCTTGTATAGTGTCCCCATGG                       GCTCCCACTGCAGCCTCGACTGCCCCTGTCCCACCTGGCTCCCCCTGCTGGTGTCTAGTGTTTTTT                       TCCCTCTCCTGTCCTTGTGTTGAAGGCAGTAAACTAAGGGTGTCAAGCCCCATTCCCTCTCTACTC                       TTGACAGCAGGATTGGATGTTGTGTATTGTCGTTTATTTTATTTTCTTCATTTTGTTCTGTtTTTA                       AAGTATGCAAAATAAAGAATATGCCGTTTTTA                                           ORF Start: ATG at 85       ORF Stop: TAG at 2257           SEQ ID NO:120   724 aa   MW at 83293.4 kD                     NOV22d,   MPEEVHHGEEEVETFAFQAETAQLMSLIINTFYSNKEIFLRELISNASDALDKTRYESLTDPSKLD       CG56618-01       Protein Sequence   SGKELKIDIIPMPQERTLTLVDTGIGMTKADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVG                   FYSAYLVAEKVVVIRKHNDDEQYAWESSAGGSFTVRADHGEPIGMGTKVILHLKEDQTEYLEERRV                   KEVVKKHSQFIGYPITLYLEKEREKEISDDEAEEEKGEKEEEDKDDEEKPKIEDVGSDEEDDSGKD                   KKKKTKKIKEKYIDQEELNKTKPIWTRNPDDITQEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFR                   ALLFIPRRAPFDLFENKKKKNNIKLYVRRVFIMDSCDELIPEYLNFIRGVVDSEDLPLNISREMLQ                   QSKILKVIRKNIVKKCLELFSELAEDKENYKKFYEAFSKNLKLGIHEDSTMRRRLSELLRYHTSQS                   GDEMTSLSEYVSRMETQKSIYYITGESKEQVANSAFVERVRKRGFEVVYMTEPTDEYCVQQQLKEF                   DGKSLVSVTKEGLELPEDEEEKKKMEESKAKFEMLCKLMKEILDKKVEKVTISNRLVSSPCCIVTS                   TYGWTANMERIMKAQALRDNSTMGYMMAKKHLEINPDHPIVETLRQKAEADKNDKAVKDLVVLLFE                   TALLSSGFSLEDPQTHSNRIYRMIKLGLGIDEDEVAAEEPNAAVPDEIPPLEGDEDASRMEEVD                  
 
     [0476] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 22B.  
               TABLE 22B                          Comparison of NOV22a against NOV22b through NOV22d.                                         Identities/                   Similarities for           Protein   NOV22a Residues/   the Matched           Sequence   Match Residues   Region                       NOV22b   550 . . . 723    172/174 (98%)               142 . . . 315    174/174 (99%)           NOV22c   1 . . . 621   619/621 (99%)               2 . . . 622   620/621 (99%)           NOV22d   1 . . . 723   719/723 (99%)               2 . . . 724   720/723 (99%)                      
 
     [0477] Further analysis of the NOV22a protein yielded the following properties shown in Table 22C.  
               TABLE 22C                       Protein Sequence Properties NOV22a                                        SignalP analysis:   No Known Signal Sequence Predicted       PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 10; pos. chg 0; neg. chg 5           H-region: length 1; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −7.04           possible cleavage site: between 49 and 50           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 1           Number of TMS(s) for threshold 0.5: 1                                         INTEGRAL   Likelihood =   −2.50   Transmembrane   653-669           PERIPHERAL   Likelihood =     1.48 (at 129)                         ALOM score: −2.50 (number of TMSs: 1)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 660           Charge difference: 1.5 C(1.5)-N(0.0)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt; Single TMS is located near the C-terminus           &gt;&gt;&gt; membrane topology: type Nt (cytoplasmic tail 1 to 652)           MITDISC: discrimination of mitochondrial targeting seq                                         R content:   0   Hyd Moment(75):   6.77               Hyd Moment(95):   5.71   G content:   0           D/E content:   2   S/T content:   0           Score: −7.00                         Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: KKKK (5) at 346           pat7: none           bipartite: none           content of basic residues: 14.7%           NLS Score: −0.16           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: too long tail           Dileucine motif in the tail: found           LL at 331           LL at 453           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 70.6           COIL: Lupas&#39;s algorithm to detect coiled-coil regions                                         213 L   0.55                       214 Y   0.78           215 L   0.94           216 E   0.94           217 K   0.94           218 E   0.94           219 R   0.94           220 E   0.94           221 K   0.94           222 E   0.94           223 I   0.94           224 S   0.94           225 D   0.94           226 D   0.94           227 E   0.94           228 A   0.94           229 E   0.94           230 E   0.94           231 E   0.94           232 K   0.94           233 G   0.94           234 E   0.94           235 K   0.94           236 E   0.94           237 E   0.94           238 E   0.94           239 D   0.94           240 K   0.94           241 D   0.94           242 D   0.94           243 E   0.78           244 E   0.78           245 K   0.78           540 E   0.79           541 L   0.79           542 P   0.79           543 E   1.00           544 D   1.00           545 E   1.00           546 E   1.00           547 E   1.00           548 K   1.00           549 K   1.00           550 K   1.00           551 M   1.00           552 E   1.00           553 E   1.00           554 S   1.00           555 K   1.00           556 A   1.00           557 K   1.00           558 F   1.00           559 E   1.00           560 N   1.00           561 L   1.00           562 C   1.00           563 K   1.00           564 L   1.00           565 M   1.00           566 K   1.00           567 E   1.00           568 I   1.00           569 L   1.00           570 D   1.00           571 K   1.00           572 K   1.00           573 V   0.95           574 E   0.95           575 K   0.78           576 V   0.74                         total: 70 residues           Final Results (k = 9/23):           26.1%: cytoplasmic           26.1%: nuclear           13.0%: Golgi           13.0%: endoplasmic reticulum            8.7%: mitochondrial            8.7%: vesicles of secretory system            4.3%: peroxisomal           &gt;&gt; prediction for CG56618-02 is cyt (k = 23)                  
 
     [0478] 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 22D.  
               TABLE 22D                          Geneseq Results for NOV22a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV22a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value                                         ABB06994   Human Hsp90 beta protein SEQ ID   1 . . . 723   719/723 (99%)   0.0           NO: 1 -  Homo sapiens , 724 aa.   2 . . . 724   720/723 (99%)           [WO200215925-A1, 28 FEB. 2002]       AAB36507   Human Hsp90 beta protein sequence   1 . . . 723   719/723 (99%)   0.0           SEQ ID NO: 6 -  Homo sapiens , 724   2 . . . 724   720/723 (99%)           aa. [WO200068693-A2,           16 NOV. 2000]       AAB82537   Human heat shock protein Hsp84 -   1 . . . 723   719/723 (99%)   0.0             Homo sapiens , 724 aa.   2 . . . 724   720/723 (99%)           [WO200152791-A2, 26 JUL. 2001]       AAE12989   Human Hsp90 family homologue,   1 . . . 723   719/723 (99%)   0.0           Hsp84 -  Homo sapiens , 724 aa.   2 . . . 724   720/723 (99%)           [US2001034042-A1, 25 OCT. 2001]       AAB82536   Human heat shock protein Hsp86 -   8 . . . 723   622/719 (86%)   0.0             Homo sapiens , 732 aa.   14 . . . 732    679/719 (93%)           [WO200152791-A2, 26 JUL. 2001]                  
 
     [0479] In a BLAST search of public sequence databases, the NOV22a protein was found to have homology to the proteins shown in the BLASTP data in Table 22E.  
               TABLE 22E                          Public BLASTP Results for NOV22a                                             Identities/           Protein           Similarities for       Accession       NOV22a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value                                         P08238   Heat shock protein HSP 90-beta (HSP   1 . . . 723   721/723 (99%)   0.0           84) (HSP 90) -  Homo sapiens     1 . . . 723   722/723 (99%)           (Human), 723 aa.       CAC18968   Sequence 5 from Patent WO0068693 -   1 . . . 723   719/723 (99%)   0.0             Homo sapiens  (Human), 724 aa.   2 . . . 724   720/723 (99%)       HHMS84   heat shock protein 84 - mouse, 724 aa.   1 . . . 723   718/723 (99%)   0.0               2 . . . 724   721/723 (99%)       P11499   Heat shock protein HSP 90-beta (HSP   1 . . . 723   715/723 (98%)   0.0           84) (Tumor specific transplantation 84   1 . . . 723   719/723 (98%)           kDa antigen) (TSTA) -  Mus musculus             (Mouse), 723 aa.       E980235     H. SAPIENS  HSP90 SEQUENCE -   1 . . . 723   717/723 (99%)   0.0             Homo sapiens  (Human), 724 aa.   2 . . . 724   718/723 (99%)                  
 
     [0480] PFam analysis predicts that the NOV22a protein contains the domains shown in the Table 22F.  
               TABLE 22F                          Domain Analysis of NOV22a                                             Identities/                   NOV22a   Similarities for           Pfam   Match   the Matched   Expect           Domain   Region   Region   Value                       HATPase_c   34 . . . 188    23/165 (14%)   1.7e−11                   105/165 (64%)           HSP90   190 . . . 723    383/543 (71%)   0                   519/543 (96%)                      
 
     Example 23.  
     [0481] 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:121   2442 bp                     NOV23a,     TGCAGTTGCTTCCTTTCCTTGAAGGTAGCTGTATCTTATTTTCTTTAAAAAGCTTTTTCTTCCAAA         CG57509-01       DNA Sequence     GCCACTTGCC   ATG CCGACCGTCATTAGCGCATCTGTGGCTCCAAGGACAGCGGCTGAGCCCCGGTC                   CCCAGGGCCAGTTCCTCACCCGGCCCAGAGCAAGGCCACTGAGGCTGGGGGTGGAAACCCAAGTGG                   CATCTATTCAGCCATCATCAGCCGCAATTTTCCTATTATCGGAGTGAAAGAGAAGACATTCGAGCA                   ACTTCACAAGAAATGTCTAGAAAAGAAAGTTCTTTATGTGGACCCTGAGTTCCCACCGGATGAGAC                   CTCTCTCTTTTATAGCCAGAAGTTCCCCATCCAGTTCGTCTGGAAGAGACCTCCGGAAATTTGCGA                   GAATCCCCGATTTATCATTGATGGAGCCAACAGAACTGACATCTGTCAAGGAGAGCTAGGGGACTG                   CTGGTTTCTCGCAGCCATTGCCTQCCTGACCCTGAACCACCACCTTCTTTTCCGAGTCATACCCCA                   TGATCAAAGTTTCATCGAAAACTACGCAGGGATCTTCCACTTCCAGTTCTGGCGCTATGGAGAGTG                   GGTGGACGTGGTTATAGATGACTGCCTGCCAACGTACAACAATCAACTGGTTTTCACCAAGTCCAA                   CCACCGCAATGAGTTCTGGAGTGCTCTGCTGGAGAAGGCTTATGCTAAGCTCCATGGTTCCTACGA                   AGCTCTGAAAGGTGGGAACACCACAGAGGCCATGGAGGACTTCACAGGAGGGGTGGCAGAGTTTTT                   TGAGATCAGGGATGCTCCTAGTGACATGTACAAGATCATGAAGAAAGCCATCGAGAGAGGCTCCCT                   CATGGGCTGCTCCATTGATACAATCATTCCGGTTCAGTATGAGACAAGAATGGCCTGCGGGCTGGT                   CAGAGGTCACGCCTACTCTGTCACGGGGCTGGATGAGGTCCCGTTCAAAGGTGAGAAAGTGAAGCT                   GGTGCCGCTCCGGAATCCGTGGGGCCAGGTGGAGTGGAACGGTTCTTGGAGTGATAGATGGAAGGA                   CTGGAGCTTTGTCGACAAAGATGAGAAGGCCCGTCTGCAGCACCAGGTCACTGAGGATGAGAAGTT                   CTGGATGTCCTATGAGGATTTCATCTACCATTTCACAAAGTTGGAGATCTGCAACCTCACGGCCGA                   TGCTCTGCAGTCTGACAAGCTTCAGACCTGGACAGTGTCTGTCAACGAGGGCCGCTGGGTACGGGG                   TTGCTCTGCCGGAGGCTGCCGCAACTTCCCAGATACTTTCTGGACCAACCCTCAGTACCGTCTGAA                   GCTCCTGGAGGAGGACGATGACCCTGATGACTCGGAGGTGATTTGCAGCTTCCTGCTGGCCCTGAT                   GCAGAAGAACCGGCGGAAGGACCGGAAQCTAGGGGCCAGTCTCTTCACCATTGGCTTCGCCATCTA                   CGAGGTTCCCAAAGAGATGCACGGGAACAAGCAGCACCTGCAGAAGGACTTCTTCCTGTACAACGC                   CTCCAAGGCCAGGAGCAAAACCTACATCAACATGCGGGAGGTGTCCCAGCGCTTCCCCCTGCCTCC                   CAGCGAGTACGTCATCGTGCCCTCCACCTACGAGCCCCACCAGGAGGGGGAATTCATCCTCCGGGT                   CTTCTCTGAAAAGAGGAACCTCTCTGAGGAAGTTGAAAATACCATCTCCGTGGATCGGCCAGTCAA                   AAAGAAAAAAACCAAGCCCATCATCTTCGTTTCGGACAGAGCAAACAGCAACAAGGAGCTGGGTGT                   GGACCAGGAGTCAGAGGAGGGCAAAGGCAAAACAAGCCCTGATAAGCAAAAGCAGTCCCCACAGCC                   ACAGCCTGGCAGCTCTGATCAGGAAAGTGAGGAACAGCAACAATTCCGGAACATTTTCAAGCAGAT                   AGCAGGAGATGACATGGAGATCTGTGCAGATGAGCTCAAGAAGGTCCTTAACACAGTCGTGAACAA                   ACACAAGGACCTGAAGACACACGOGTTCACACTGGAGTCCTGCCGTAGCATGATTGCGCTCATGGA                   TACAGATGGCTCTGGAAAGCTCAACCTGCAGGAGTTCCACCACCTCTGGAACAAGATTAAGGCCTG                   GCAGAAAATTTTCAAACACTATGACACAGACCAGTCCGGCACCATCAACAGCTACGAGATGCGAAA                   TGCAGTCAACGACGCAGGATTCCACCTCAACAACCAGCTCTATGACATCATTACCATGCGGTACGC                   AGACAAACACATGAACATCGACTTTGACAGTTTCATCTGCTGCTTCGTTAGGCTGGAGGGCATGTT                   CAGAGCTTTCATGCATTTGACAAGGATGGAGATGGTATCATCAAGCTCAACGTTCTGGAGTTGGCT                   GCAGCTCACCATGTATGCCTGAACCAGGCTCOCCTCATCCAAAGCCATGCACGATCACTCACGATT                                         ORF Start: ATG at 77       ORF Stop: TGA at 2396           SEQ ID NO:122   773 aa   MW at 88985.0 kD                     NOV23a,   MPTVISASVAPRTAAEPRSPGPVPHPAQSKATEAGGGNPSGIYSAIISRNFPIIGVKEKTFEQLHK       CG57509-01       Protein Sequence   KCLEKKVLYVDPEFPPDETSLFYSQKFPIQFVWKRPPEICENPRFIIDGANRTDICQGELGDCWFL                   AAIACLTLNQHLLFRVIPHDQSFIENYAGIFHFQFWRYGEWVDVVIDDCLPTYNNQLVFTKSNHRN                   EFWSALLEKAYAKLHGSYEALKGGNTTEAMEDFTGGVAEFFEIRDAPSDMYKIMKKAIERGSLMGC                   SIDTIIPVQYETRMACGLVRGHAYSVTGLDEVPFKGEKVKLVRLRNPWGQVEWNGSWSDRWKDWSF                   VDKDEKARLQHQVTEDGEFWMSYEDFIYHFTKLEICNLTADALQSDKLQTWTVSVNEGRWVRGCSA                   GGCRNFPDTFWTNPQYRLKLLEEDDDPDDSEVICSFLVALMQKNRRKDRKLGASLFTIGFAIYEVP                   KEMHGNKQHLQKDFFLYNASKARSKTYINMREVSQRFRLPPSEYVIVPSTYEPHOECEFILRVFSE                   KRNLSEEVENTISVDRPVKKKKTKPIIFVSDRANSNKELGVDQESEEGKGKTSPDKQKQSPQPQPG                   SSDQESEEQQQFRNIFKQIAGDDMEICADELKKVLNTVVNKHKDLKTHGFTLESCRSMIALMDTDG                   SGKLMLQEFHHLWNKIKAWQKIFKHYDTDQSGTINSYEMRNAVNDAGFHLNNQLYDIITMRYADKH                   MNIDFDSFICCFVRLEGMFRAFHAFDKDGDGIIKLNVLEWLQLTMYA                                     SEQ ID NO:123   2469 bp                     NOV23b,   TATGCCGACCGTCATTAGCGCATCTGTGGCTCCAAGGACAGCGGCTGAGCCCCGGTCCCCAGGGCCA       CG57509-02       DNA Sequence   GTTCCTCACCCGGCCCAGAGCAAGGCCACTGAGGCTGGGGGTGGAAACCCAAGTGGGCATCTATTCA                   GCCATCATCAGCCGCAATTTTCCTATTATCGGAGTGAAAGAGAAGACATTCGAGCAACTTCACAAG                   AAATGTCTAGAAAAGAAAGTTCTTTATGTGGACCCTGAGTTCCCACCGGATGAGACCTCTCTCTTT                   TATAGCCAGAAGTTCCCCATCCAGTTCGTCTGGAAGAGACCTCCGGAAATTTGCGAGAATCCCCGA                   TTTATCATTGATGGAGCCAACAGAACTGACATCTGTCAAGGAGAGCTAGGGGACTGCTGGTTTCTC                   GCAGCCATTGCCTGCCTGACCCTGAACCAGCACCTTCTTTTCCGAGTCATACCCCATGATCAAAGT                   TTCATCGAAAACTACGCAGGGATCTTCCACTTCCAGTTCTGGCGCTATGGAGAGTGAATGGACGTG                   GTTATAGATGACTGCCTGCCAACGTACAACAATCAACTGGTTTTCACCAAGTCCAACCACCGCAAT                   GAGTTCTGGAGTGCTCTGCTGGAGAAGGCTTATGCTAAGCTCCATGGTTCCTACGAAGCTCTGAAA                   GGTGGGAACACCACAGAGGCCATGGAGGACTTCACAGGAGGGGTOGCAGAGTTTTTTGAGATCAGG                   GATGCTCCTAGTGACATGTACAAGATCATGAAGAAAGCCATCGAGAGAGGCTCCCTCATAAACTGC                   TCCATTGATGATCGCACGAACATGACCTATGGAACCTCTCCTTCTGGTCTGAACATAAGCGAGTTG                   ATTGCACGGATGGTAAGGAATATGGATAACTCACTGCTCCAGGACTCAGACCTCGACCCCAGAAAC                   TCAGATGAAAGACCGACCCGGACAATCATTCCGGTTCAGTATGAGACAAGAATGGCCTGCGGGCTG                   GTCAGAGGTCACGCCTACTCTCTCACGGGGCTGGATGAGGTCCCGTTCAAGGTGAGAAAGTGAAAG                   CTGGTGCGGCTGCCGAATCCGTGGGGCCAGGTGGACTCGAACGGTTCTTGGAGTGATAGATGGAAG                   GACTGGAGCTTTGTGGACAAAGATGAGAAGGCCCGTCTGCAGCACCAGGTCACTGAGGATGGAGAG                   TTCTGGATGTCCTATGAGGATTTCATCTACCATTTCACAAGTTGGAGATCTGCAACCTCACAAACC                   GATGCTCTGCAGTCTGACAAGCTTCAGACCTGGACAGTGTCTGTGAACGAGGGCCGCTGGGTACGG                   GGTTGCTCTGCCCGAGGCTGCCGCAACTTCCCAGATACTTTCTGGACCAACCCTCAGTACCGTCTG                   AAGCTCCTGGAGGAGGACGATGACCCTGATGACTCGGAGGTGATTTGCAGCTTCCTGGTGGCCCTG                   ATGCAGAAGAACCGGCGGAAGGACCGGAAGCTAGGGGCCAGTCTCTTCACCATTGGCTTCGCCATC                   TACGAGGTTCCCAAGAGATGCACGGGAACAAGCAGCACCTGCAGAAGGACTTCTTCCTGTACAAAC                   GCCTCCAAGGCCAGGAGCAAAACCTACATCAACATGCGGGAGGTGTCCCAGCCCTTCCGCCTGCCT                   CCCAGCGAGTACGTCATCGTGCCCTCCACCTACGAGCCCCACCAGGAGGGGGAATTCATCCTCCGG                   GTCTTCTCTGAAAAGAGGAACCTCTCTGAGGAAGTTGAAAATACCATCTCCGTGGATCGGCCAGTG                   AAAAAGAAAAAAACCAAGCCCATCATCTTCGTTTCGGACAGAGCAAACAGCAACAAGGAGCTGGGT                   GTGGACCAGGAGTCAGAGGAGGGCAAAGGCAAAACAAGCCCTGATAAGCAAAAGCAGTCCCCACAG                   CCACAGCCTGGCAGCTCTGATCAGGAAAGTGAGGAACAGCAACAATTCCGGAACATTTTCAAGCAG                   ATAGCAGGAGATGACATGGAGATCTGTGCAGATGAGCTCAAGAAGGTCCTTAACACAGTCGTGAAC                   AGACACAAGGACCTGAAGACACACGGGTTCACACTGGAGTCCTGCCGTAGCATGATTGCGCTCATG                   GATACAGATGGCTCTGGAAGCTCAACCTGCAGGAGTTCCACCACCTCTGGAACAAAGATTGGGACC                   TCGCAGAAAATTTTCAAACACTATGACACAGACCAGTCCGCCACCATCAACAGCTACGAGATGCGA                   AATGCAGTCAACGACGCAGGATTCCACCTCAACAACCAGCTCTATGACATCATTACCATGCGGTAC                   GCAGACAACACATGAACATCGACTTTGACAGTTTCATCTGCTGCTTCGTTAGGCTAAAAGGGCATG                   TTCAGAGCTTTTCATGCATTTGACAAGOATGGAGATGGTATCATCAAGCTCAACGTTCTGGAGTGG                   CTGCAGCTCACCATGTATGCCTGA AAA                                           ORF Start: ATG at 1       ORF Stop: TGA at 2464           SEQ ID NO:124   821 aa   MW at 94252.7 kD                     NOV23b,   MPTVISASVAPRTAAEPRSPGPVPHPAQSKATEAGGGNPSGIYSAIISRNFPIIGVKEKTFEQLHK       CG57509-02       Protein Sequence   KCLEKKVLYVDPEWPPDETSLFYSQKFPIQFVWKRPPEICENPRFIIDGANRTDICQGELGDCWFL                   AAIACLTLNQHLLFRVIPHDQSFIENYAGIFHFQFWRYGEWVDVVIDDCLPTYNNQLVFTKSWHRN                   EFWSALLEKAYAKLHGSYEALKGGNTTEAMEDFTGGVAEFFEIRDAPSDMYKIMKKAIERGSLMGC                   SIDDGTNNTYGTSPSGLNMGELIARMVRNNDNSLLQDSDLDPRGSDERPTRTIIPVQYETRMACGL                   VRGHYSVTGLDEVPFKGEKVKALVRLRNPWGQVEWNGSWSDRWKDWSFVDKDEKARLQHQVTEDGE                   FWMSYEDFIYHFTKLEICNLTADALQSDKLOTWTVSVNEGRWVRGCSAGGCRNFPDTFWTNPQYRL                   KLLEEDDDPDOSEVICSFLVALMOKNRRKDRKLGASLFTIGGAIYEVPKEMHGNKQHLQKDFFLYN                   ASKARSKTYINMREVSQRFRLPPSEYVIVPSTYEPHQEGEFILRVFSEKRNLSEEVENTISVDRPV                   KKKKTPHIIFVSDRANSNKELGVDQESEEGKGKTSPDKQKQSPQPQPGSSDQESEEQQQFRNIFKQ                   IAGDDMETCADELKKVLNTVVNRHKDLKTHCFTLESCRSMIALMDTDGSOGNLQEFHHLWNKIGKA                   WQKIFKHYDTDQSGTINSYEMRNAVNDAGFHLNNQLYDIITMRYADKHMNIDFDSFICCFVRLEGM                   FRAFHAFDKDGDGIIKLNVLEWLQLTMYA                  
 
     [0482] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 23B.  
               TABLE 23B                          Comparison of NOV23a against NOV23b.                                         Identities/                   Similarities for           Protein   NOV23a Residues/   the Matched           Sequence   Match Residues   Region                       NOV23b   1 . . . 773   773/821 (94%)               1 . . . 821   773/821 (94%)                      
 
     [0483] Further analysis of the NOV23a protein yielded the following properties shown in Table 23C.  
               TABLE 23C                       Protein Sequence Properties NOV23a                                        SignalP analysis:   Cleavage site between residues 16 and 17       PSORT II analysis:   PSG: a new signal peptide prediction method           N-region: length 0; pos. chg 0; neg. chg 0           H-region: length 11; peak value 7.27           PSG score: 2.87           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −5.40           possible cleavage site: between 15 and 16           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 0.90 (at 130)           ALOM score: 0.90 (number of TMSs: 0)           MTOP: Prediction of membrane topology (Hartmann et al.)           Center position for calculation: 6           Charge difference: 0.5 C(1.5)-N(1.0)           C &gt; N: C-terminal side will be inside           &gt;&gt;&gt;Caution: Inconsistent mtop result with signal peptide           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   1   Hyd Moment(75):   1.57           Hyd Moment(95):   2.73   G content:   0           D/E content:   1   S/T content:   4                         Score: −3.90           Gavel: prediction of cleavage sites for mitochondrial preseq           R-2 motif at 59 SRN|FP           NUCDISC: discrimination of nuclear localization signals           pat4: KKKK (5) at 547           pat7: PVKKKKT (5) at 545           bipartite: none           content of basic residues: 12.4%           NLS Score: 0.27           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 89           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           47.8%: cytoplasmic           26.1%: mitochondrial           21.7%: nuclear           4.3%: vacuolar           &gt;&gt; prediction for CG57509-01 is cyt (k = 23)                  
 
     [0484] 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 23D.  
               TABLE 23D                          Geneseq Results for NOV23a                                             Identities/                       Similarities for       Geneseq   Protein/Organism/Length   NOV23a Residues/   the Matched   Expect       Identifier   [Patent #, Date]   Match Residues   Region   Value                                         AAE19164   Human protease, PRTS-1 protein -    1 . . . 773   766/773 (99%)   0.0             Homo sapien s, 767 aa.    1 . . . 767   766/773 (99%)           [WO200208396-A2, 31 JAN. 2002]       AAR99579   Calpain large subunit 1 -  Homo      1 . . . 773   773/821 (94%)   0.0             sapiens , 821 aa. [WO9616175-A2,    1 . . . 821   773/821 (94%)           30 MAY 1996]       AAY30342   A calpain protein specific for eye   61 . . . 773   613/765 (80%)   0.0           tissue retina - Rattus sp, 757 aa.   37 . . . 757   638/765 (83%)           [WO9945107-A1, 10 SEP. 1999]       ABG26746   Novel human diagnostic   58 . . . 765   606/776 (78%)   0.0           protein #26737 -  Homo sapiens , 1069 aa.   258 . . . 1005   619/776 (79%)           [WO200175067-A2, 11 OCT. 2001]       AAE23085   Calcium-activated neutral protease   61 . . . 773   371/720 (51%)   0.0           protein - Unidentified, 713 aa.   42 . . . 713   504/720 (69%)           [WO200203787-A2, 17 JAN. 2002]                  
 
     [0485] In a BLAST search of public sequence databases, the NOV23a protein was found to have homology to the proteins shown in the BLASTP data in Table 23E.  
               TABLE 23E                          Public BLASTP Results for NOV23a                                             Identities/           Protein           Similarities for       Accession       NOV23a Residues/   the Matched   Expect       Number   Protein/Organism/Length   Match Residues   Portion   Value                                         O08702   Calpain Lp82 -  Rattus norvegicus     61 . . . 773   613/717 (85%)   0.0           (Rat), 709 aa.   37 . . . 709   638/717 (88%)       O88977   Calpain Lp82 -  Mus musculus     61 . . . 773   607/717 (84%)   0.0           (Mouse), 709 aa.   37 . . . 709   637/717 (88%)       Q9XSJ3   Lens-specific calpain Lp82 -   61 . . . 773   601/717 (83%)   0.0             Oryctolagus cuniculus  (Rabbit), 709   37 . . . 709   634/717 (87%)           aa.       Q9XSJ1   Lens-specific calpain Lp82 -  Bos     61 . . . 773   602/717 (83%)   0.0             taurus  (Bovine), 709 aa.   37 . . . 709   633/717 (87%)       Q9XSJ2   Lens-specific calpain Lp82 -  Sus     61 . . . 773   604/717 (84%)   0.0             scrofa  (Pig), 709 aa.   37 . . . 709   633/717 (88%)                  
 
     [0486] PFam analysis predicts that the NOV23a protein contains the domains shown in the Table 23F.  
               TABLE 23F                          Domain Analysis of NOV23a                                             Identities/                   NOV23a   Similarities for           Pfam   Match   the Matched   Expect           Domain   Region   Region   Value                       Peptidase_C2    74 . . . 369   198/344 (58%)   7.2e−213                   293/344 (85%)           Calpain_III   380 . . . 534   100/163 (61%)   5.5e−107                   147/163 (90%)           efhand   648 . . . 676     8/29 (28%)   0.00023                    25/29 (86%)           efhand   678 . . . 706     8/29 (28%)   0.0005                    24/29 (83%)                      
 
     Example 24.  
     [0487] 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:125   3071 bp                     NOV24a,     TTCCAGCCGCCAGG   ATG GAGGACGAGGAAGGCCCTGAGTATGGCACCTGACTTTGTGCTTTTGG       CG59522-02       DNA Sequence   ACCAAGTGACCATGGAGGACTTCATGAGGAACCTGCAGCTCAGGTTCGAGAAGGGCCGCATCTACA                   CCTACATCGGTGAGGTGCTGGTGTCCGTGAACCCCTACCAGGAGCTGCCCCTGTATGGGCCTGAGG                   CCATCGCCAGGTACCAGGGCCGTGAGCTCTATGAGCGGCCACCCCATCTCTATGCTGTGGCCAACG                   CCGCCTACAAGGCAATGAAGTACCGGTCCAGAACACCTGCATCGTAATCTCAGGGGAGAGTGGGGG                   CAGGGAAGACAGAAGCCAGTAAGCACATCATGCAGTACATCGCTGCTGTCACCAATCCAAGCCAGA                   GGGTGAGGTGGAGAGGGTCAGGACGTGCTGCTCAGTCCACCTGTGTGCTGGAACCTTTGGGGCAGA                   ATGCCCGCACCAACCGCAATCACAACTCCAGCCGCTTTGGCAAGTACATGGACATCAACTTTGACT                   TCAAGGGGGACCCGATCGGAGGACGCATCCACAGCTACCTACTGGAGAAGTCTCGGGTCCTCAAGC                   TCAAGGGGGACCCGATCGGAGGACGCATCCACAGCTACCTACTGGAGAAGTCTCGGGTCCTCAAGC                   AGCACGTGGGTGAAAGAAACTTCCACGCCTTCTACCAATTGCTGAGAGGCAGTGAGGACAAGCAGC                   TGCATGAACTGCACTTGGAGAGAAACCCTGCTGTATACAATTTCACACACCAGGGAGCAGGACTCA                   ACATGACTGTGCACAGTGCCTTGGACAGTGATGAGCAGAGCCACCAGGCAGTGACCGAGGCCATGA                   GGGTCATCGGCTTCAGTCCTGAAGAGGTGGAGTCTGTGCATCGCATCCTGGCTGCCATATTGCACC                   TGGGAAACATCGAGTTTGTGGAGACGGAGGAGGGTGGGCTGCAGAAGGAGGGCCTGGCAGTGGCCG                   AGGAGGCACTGGTGGACCATGTGGCTGAGCTGACGGCCACACCCCGGGACCTCGTGCTCCGCTCCC                   TGCTGGCTCGCACAGTTGCCTCGGGAGGCAGGGAACTCATAGAGAAGGGCCACACTGCAGCTGAGG                   CCAGCTATGCCCGGGATGCCTGTGCCAAGGCAGTGTACCAGCGGCTGTTTGAGTGGGTGGTGAACA                   GGATCAACAGTGTCATGGAACCCCGGGGCCGGGATCCTCGGCGTGATGGCAAGGACACAGTCATTG                   GCGTGCTGGACATCTATGGCTTCGAGGTGTTTCCCGTAACAGTTTCGAGAAGTTCTGCATCAAGCT                   ACTGCAATGAGAAGCTGCAGCAGCTATTCATCCAGCTCATCCTGGGGCAAACAGGAAGGGAGTACG                   AGCGCGAGGGCATCACCTGGCAGAGCGTTGAGTATTTCAACAACGCCACCATTGTGGATCTGGTGG                   AGCGGCCCCACCGTGGCATCCTGGCCGTGCTGGACGAGGCCTGCAGCTCTGCTGGCACCATCACTG                   ACCGAATCTTCCTGCAGACCCTCGACACGCACCACCGCCATCACCTACACTACACAAGCCGCCAGC                   TCTGCCCCACAGACAAGACCATGGAGTTTGGCCGAGACTTCCGGATCAAGCACTATGCAGGGGACG                   TCACGTACTCCGTGGAAGGCTTCATCGACAAGAACAGAGATTTCCTCTTCCAGGACTTCAAGCGGC                   TGCTGTACAACAGCACGGACCCCACTCTACGGGCCATGTGGCCGGACGGGCAGCAGGACATCACAG                   AGGTGACCAAGCGCCCCCTGACGGCTGGCACACTCTTCAAGAACTCCATGGTGGCCCTGGTGGAGA                   ACCTTGCCTCCAAGGAGCCCTTCTACGTCCGCTGCATCAAGCCCAATGAGGACAAGGTAGCTGGGA                   AGCTGGATGAGAACCACTGTCGCCACCAGGTCGCATACCTGGGGCTGCTGGAGAATGTGAGGGTCC                   GCAGGGCTGGCTTCGCTTCCCGCCAGCCCTACTCTCGATTCCTGCTCAGGTACAAGATGACCTGTG                   AATACACATGGCCCAACCACCTGCTGGGCTCCGACGGCAGCCGTGAGCGCTCTCCTAAGCGGGAGC                   ACGGGCTGCAGGGGGACGTGGCCTTTGGCCACAGCAAGCTGTTCATCCGCTCACCCCGGACACTGG                   TCACACTGGAGCAGAGCCGAGCCCGCCTCATCCCCATCATTGTGCTGCTATTGCAGAAGGCATGGC                   GGGGCACCTTGGCGAGGTGGCGCTGCCGGAGGCTGAGGGCTATCTACACCATCATGCGCTGGTTCC                   GGAGACACAAGGTGCGGGCTCACCTGGCTGAGCTGCAGCGGCGATTCCAGGCTGCAAAACAGCCGC                   CACTCTACGGGCGTGACCTTGTGTGGCCGCTGCCCCCTGCTGTGCTGCAGCCCTTCAAGACAGCCT                   GCCACGCACTCTTCTGCAGGTGGCGGGCCCGGCAGCTGGTGAAGAACATCCCCCCTTCAGACATGC                   CCCAGATCAAGGCCAAGGTGGCCGCCATGGGGGCCCTGCAAGGGCTTCGTCAGGACTGGGGCTGCC                   GACGGGCCTGGGCCCGAGACTACCTGTCCTCTGCCACTGACAATCCCACAGCATCAAGCCTGTTTG                   CTCAGCGACTAAAGACACTTCGGGACAAAGATGGCTTCGGGGCTGTGCTCTTTTCAAGCCATGTCC                   GCAAGGTGAACCGCTTCCACAAGATCCGGAACCGGGCCCTCCTGCTCACAGACCAGCACCTCTACA                   AGCTGGACCCTGACCGGCAGTACCGGGTGATGCGGGCCGTGCCCCTTGAGGCGGTGACGGGGCTGA                   GCGTGACCAGCGGAGGAGACCAGCTGGTGGTGCTGCACGCCCGCGGCCAGGACGACCTCGTGGTGT                   GCCTGCACCGCTCCCGGCCGCCATTGGACAACCGCGTTGGGGAGCTGGTGGGCGTGCTGGCCGCAC                   ACTGCCAGGGGGAGGGCCGCACCCTGGAGGTTCGCGTCTCCGACTGCATCCCACTAAGCCATCGCG                   GGGTCCGGCGCCTCATCTCCCTCGAGCCCAGGCCGGAGCAGCCAGAGCCCGATTTCCGCTGCGCTC                   GCGGCTCCTTCACCCTGCTCTGGCCCAGCCGC TGA                                           ORF Start: ATG at 15       ORF Stop: TGA at 3069           SEQ ID NO:126   1018 aa   MW at 116483.8 kD                     NOV24a,   MEDEEGPEYGKPDFVLLDQVTMEDFMRNLQLRFEKGRIYTYIGEVLVSVNPYQELPLYGPEAIARY       CG59522-02       Protein Sequence   QGRELYERPPHLYAVANAAYKAMKYRSRDTCIVISGESGAGKTEASKHIMQYIAAVTNPSQRAEVE                   RVKDVLLKSTCVLEAFGNARTNRNHNSSRFGKYMDINFDFKGDPIGGRIHSYLLEKSRVLKQHVGE                   RNFHAFYQLLRGSEDKQLHELHLERNPAVYNFTHQGAGLNMTVHSALDSDEQSHQAVTEAMRVIGF                   SPEEVESVHRILAAILHLGNIEFVETEEGGLQKEGLAVAEEALVDHVAELTATPRDLVLRSLLART                   VASGGRELIEKGHTAAEASYARDACAKAVYQRLFEWVVNRINSVMEPRGRDPRRDGKDTVIGVLDI                   YGFEVFPVNSFEQFCINYCNEKLQQLFIQLILKQEQEEYEREGITWQSVEYFNNATIVDLVERPHR                   GILAVLDEACSSAGTITDRIFLQTLDTHHRHHLHYTSRQLCPTDKTMEFGRDFRIKHYAGDVTYSV                   EGFIDKNRDFLFQDFKRLLYNSTDPTLRAMWPDGQQDITEVTKRPLTAGTLFKNSMVALVENLASK                   EPFYVRCIKPNEDKVAGKLDENHCRHQVAYLGLLENVRVRRAGFASRQPYSRFLLRYKMTCEYTWP                   NHLLGSDKAAVSALLEQHGLQGDVAFGHSKLFIRSPRTLVTLEQSRARLIPIIVLLLQKAWRGTLA                   RWRCRRLRAIYTIMRWFRRHKVRAHLAELQRRFQAARQPPLYGRDLVWPLPPAVLQPFQDTCHALF                   CRWRARQLVKNIPPSDMPQIKAKVAAMGALQGLRQDWGCRRAWARDYLSSATDNPTASSLFAQRLK                   TLRDKDGFGAVLFSSHVRKVNRFHKIRNRALLLTDQHLYKLDPDRQYRVMRAVPLEAVTGLSVTSG                   GDQLVVLHARGQDDLVVCLHRSRPPLDNRVGELVGVLAAHCQGEGRTLEVRVSDCIPLSHRGVRRL                   AISVEPRPEQPEPDFRCARGSFTLLWPSR                                     SEQ ID NO:127   3080 bp                     NOV24b,     TTCCAGCCGGCAGG   ATG GAGGACGAGGAAGGCCCTGAGTATGGCAAACCTGACTTTGTGCTTTTGG       CG59522-01       DNA Sequence   ACCAAGTGACCATGGAGGACTTCATGAGGAACCTGCAGCTCAGGTTCGAGAAGGGCCGCATCTACA                   CCTACATCGGTGAGGTGCTGGTGTCCGTGAACCCCTACCAGGAGCTGCCCCTGTATGGGCCTGAGG                   CCATCGCCAGGTACCAGGGCCGTGAGCTCTATGAGCGGCCACCCCATCTCTATGCTGTGGCCAACG                   CCGCCTACAAGGCAATGAAGCACCGGTCCAGGGACACCTGCATCGTCATCTCAGGGGAGAGTGGAA                   CAGGGAAGACAGAAGCCAGTAAGCACATCATGCAGTACATCGCTGCTGTCACCAATCCAAGCCAGA                   GGGCTGAGGTGGAGAGGGTCAAGGACGTGCTGCTCAAGTCCACCTGTGTGCTGGAGGCCTTTGGCA                   ATGCCCGCACCAACCGCAATCACAACTCCAGCCGCTTTGGCAAGTACATGGACATCAACTTTGACT                   TCAAGGGGGACCCGATCGGAGGACACATCCACAGCTACCTACTGGAGAAGTCTCGGGTCCTCAAGC                   AGCACGTGGGTGAAAGAAACTTCCACGCCTTCTACCAATTGCTGAGAGGCAGTGAGGACAAGCAGC                   TGCATGAACTGCACTTGGAGAGAAACCCTGCTGTATACAATTTCACACACCAGGGAGCAGGACTCA                   ACATGACTGTGACTGATGAGCAGACCCACCAGGCAGTGACCGAGACCATGAGATCATCGGGCTTCA                   GTCCTGAAGAGGTGGAGTCTGTGCATCGCATCCTGGCTGCCATATTGCACCTGGGAAACATCGAGT                   TTGTGGAGACGGAGGAGGGTGGGCTGCAGAAGGAGGGCCTGGCAGTGGCCGAGGAGGCACTGGTGG                   ACCATGTGGCTGAGCTGACGGCCACACCCCGGGACCTCGTGCTCCGCTCCCTGCTOGCTCGCACAG                   TTGCCTCGGGAGGCAGGGAACTCATAGAGAAGGGCCACACTGCAGCTGAGGCCAGCTATGCCCGGG                   ATGCCTGTGCCAAGGCAGTGTACCAGCGGCTGTTTGAGTGGGTGGTGAACAGGATCAACAGTGTCA                   TGGAACCCCGGGGCCGGGATCCTCGGCGTGATGGCAAGGACACAGTCATTGGCGTGCTGGACATCT                   ATGGCTTCGAGGTGTTTCCCGTCAACAGTTTCGAGCAGTTCTGCATCAACTACTGCAACGAGAAGC                   TGCAGCAGCTATTCATCCAGCTCATCCTGAAGCAGGAACAGGAAGAGTACGAGCGCGAGGGCATCA                   CCTGGCAGAGCGTTGAGTATTTCAACAACGCCACCATTGTGGATCTGGTGGAGCGGCCCCACCGTG                   GCATCCTGGCCGTGCTGGACGAGGCCTGCAGCTCTGCTGGCACCATCACTGACCGAATCTTCCTGC                   AGACCCTGGACATGCACCACCGCCATCACCTACACTACACCAGCCGCCAGCTCTGCCCCACAGACA                   AGACCATGGAGTTTGGCCGAGACTTCCGGATCAAGCACTATGCAGGGGACGTCACGTACTCCGTGG                   AAGGCTTCATCGACAAGAACAGAGATTTCCTCTTCCAGGACTTCAAGCGGCTGCTGTACAACAGCA                   CGGACCCCACTCTACGGGCCATGTGGCCGGACGGGCAGCAGGACATCACAGAGGTGACCAAGCGCC                   CCCTGACGGCTGGCACACTCTTCAAGAACTCCATGGTGGCCCTGGTGGAGAACCTTGCCTCCAAGG                   AGCCCTTCTACGTCCGCTGCATCAAGCCCAATGAGGACAAGGTAGCTGGGAAGCTGGATGAGAACC                   ACTGTCGCCACCAGGTCGCATACCTGGGGCTGCTGGAGAATGTGAGGGTCCGCAGGGCTGGCTTCG                   CTTCCCGCCAGCCCTACTCTCGATTCCTGCTCAGGTACAAGATGACCTGTGAATACACATGGCCCA                   ACCACCTGCTGGGCTCCGACAAGGCAGCCGTGAGCGCTCTCCTGGAGCAGCACGGGCTGCAGAAAG                   ACGTGGCCTTTGGCCACAGCAAGCTGTTCATCCGCTCACCCCGGACACTGGTCACACTGGAGCAGA                   GCCGAGCCCGCCTCATCCCCATCATTGTGCTGCTATTGCAGAAGGCATGGCGGGGCACCTTGGCGA                   GGTGGCGCTGCCGGAGGCTGAGGGCTATCTACACCATCATGCGCTGGTTCCGGAGACACGGAATGC                   GGGCTCACCTGGCTGAGCTGCAGCGGCGATTCCAGGCTGCAAGGCAGCCGCCACTCTACGGGCGTG                   ACCTTGTGTGGCCGCTGCCCCCTGCTGTGCTGCAGCCCTTCCAGGACACCTGCCACGCACTCTTCT                   GCAGGTGGCGGGCCCGGCAGCTGGTGAAGAACATCCCCCCTTCAGACATGCCCCAGATCAAGGCCA                   AGGTGGCCGCCATGGGGGCCCTGCAAGGGCTTCGTCAGGACTGGGGCTGCCGACGGGCCTGGGCCC                   GAGACTACCTGTCCTCTGCCACTGACAATCCCACAGCATCAAGCCTGTTTGCTCAGCGACTAAAGA                   CACTTCAGGACAAAGATGGCTTCGGGGCTGTGCTCTTTTCAAGCCATGTCCGCAAGGTGAACCGCT                   TCCACAAGATCCGGAACCGGGCCCTCCTGCTCACAGACCAGCACCTCTACAAGCTGGACCCTGACC                   GGCAGTACCGGGTGTGCGGGCCGTGCCCCTTGAGGCGGTGACGGGGCTGAGCGTGACCAGCGGGAG                   GAGACCAGCTGGTGGTGCTGCACGCCCGCGGCCAGGACGACCTCGTGGTGTGCCTGCACCGCTCCC                   GGCCGCCATTGGACAACCGCGTTGGGGACCTGGTGGGCGTGCTGGCCGCACACTGCCGCAGGGAAC                   GCCGCACCCTGGAGGTTCGCGTCTCCGACTGCATCCCACTCGCCATCGCGGGGTCCGGCGCGCTCA                   TCTCCGTGGAGCCCAGGCCGGAGCAGCCAGAGCCCGATTTCCGCTGCGCTCGCGGCTCCTTCACCC                   TGCTCTGGCCCAGCCGC TGA   GCGCCCGCACCCGCCGCACCCCGA                                           ORF Start: ATG at 15       ORF Stop: at 3054           SEQ ID NO:128   1013 aa   MW at 116044.5 kD                     NOV24b,   MEDEEGPEYGKPDFVLLDQVTMEDFMRNLQLRFEKGRIYTYIGEVLVSVNPYQELPLYGPEAIARY       CG59522-01       Protein Sequence   QGRELYERPPHLYAVANAAYKAMKHRSRDTCIVISGESCAGKTEASHIMQYIAAVTNPQRAEVEVE                   RVKDVLLKSTCVLEAFGNARTNRNHNSSRFGKYMDINFDFKGDPIGGHIHSYLLEKSRVLKQHVGE                   RNFHAFYQLLRGSEDKQLHELHLERNPAVYNFTHQGAGLNMTVSDEQSHQAVTEAMRVIGFSPEEV                   ESVHRILAAILHLGNIEFVETEEGGLQKEGLAVAEEALVDHVAELTATPRDLVRSLLARRTVASGG                   RELIEKGHTAAEASYARDACAKAVYQRLFEWVVNRINSVMEPRGRDPRRDGKDTVIGVLDIYGFEV                   FPVNSFEQFCINYCNEKLQQLFIQLILKQEQEEYEREGITWQSVEYFNNATIVDLVERPHRGILAV                   LDEACSSAGTITDRIFLQTLDMHHRHHLHYTSRQLCPTDKTMEFGRDFRIKHYAGDVTYSVEGFID                   KNRDFLFQDFKRLLYNSTDPTLRAMWPDGQQDITEVTKRPLTAGTLFKNSMVALVENLASKEPFYV                   RCIKPNEDKVAGKLDENHCRHQVAYLGLLENVRVRRAGFASRQPYSRFLLRYKMTCEYTWPNHLLG                   SDKAAVSALLEQHGLQGDVAFGHSKLFIRSPRTLVTLEQSRARLIPIIVLLLQKAWRGTLARWRCR                   RLRAIYTIMRWFRRHKVRAHLAELQRRFQAARQPPLYGRDLVWPLPPAVLQPFQDTCHALFCRWRA                   RQLVKNIPPSDMPQIKAKVAAMGALQGLRQDWGCRRAWARDYLSSATDNPTQSLFAQRLPKTLQDK                   DGFGAVLFSSHVRKVNRFHKIRNRALLLTDQHLYKLDPDRQYRVMRAVPLEAVTGLSVTSGGDQLV                   VLHARGQDDLVVCLHRSRPPLDNRVGELVGVLAAHCRREGRTLEVRVSDCIPLSHRGVRRLISVEP                   RPEQPEPDFRCARGSFTLLWPSR                  
 
     [0488] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 24B.  
               TABLE 24B                          Comparison of NOV24a against NOV24b.                                 Protein   NOV24a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV24b   1 . . . 1018   1007/1018 (98%)               1 . . . 1013   1010/1018 (98%)                      
 
     [0489] Further analysis of the NOV24a protein yielded the following properties shown in Table 24C.  
               TABLE 24C                       Protein Sequence Properties NOV24a                                        SignalP   No Known Signal Sequence Predicted       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 11; pos. chg 1; neg. chg 5           H-region: length 1; peak value 0.00           PSG score: −4.40           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −14.99           possible cleavage site: between 26 and 27           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 2.07 (at 709)           ALOM score: 2.07 (number of TMSs: 0)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   0   Hyd Moment(75):   8.14           Hyd Moment (95):   7.70   G content:   0           D/E content:   2   S/T content:   0                         Score: −6.58           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: RRHK (3) at 744           pat7: none           bipartite: RRLRAIYTIMRWFRRHK at 731           content of basic residues: 13.8%           NLS Score: 0.21           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: found           RILAAILHL at 274           KLQQLFIQL at 418           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs:           Leucine zipper pattern (PS00029): *** found ***           LAVAEEALVDHVAELTATPRDL at 300           none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 89           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           43.5%: nuclear           34.8%: cytoplasmic           17.4%: mitochondrial           4.3%: endoplasmic reticulum           &gt;&gt; prediction for CG59522-02 is nuc (k = 23)                  
 
     [0490] 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       Geneseq   Protein/Organism/Length [Patent   Match   for the   Expect       Identifier   #, Date]   Residues   Matched Region   Value               AAU23125   Novel human enzyme polypeptide   1 . . . 1018   1016/1018 (99%)    0.0           #211 -  Homo sapiens , 1026 aa.   9 . . . 1026   1017/1018 (99%)            [WO200155301-A2, 02 AUG. 2001]       AAU23128   Novel human enzyme polypeptide   1 . . . 858    855/858 (99%)   0.0           #214 -  Homo sapiens , 909 aa.   9 . . . 866    856/858 (99%)           [WO200155301-A2, 02 AUG. 2001]       ABB71113     Drosophila melanogaster     8 . . . 1017   501/1018 (49%)    0.0           polypeptide SEQ ID NO 40131 -   6 . . . 1007   682/1018 (66%)              Drosophila melanogaster , 1011 aa.           [WO200171042-A2, 27 SEP. 2001]       AAM80123   Human protein SEQ ID NO 3769 -   248 . . . 1016    438/769 (56%)   0.0             Homo sapiens , 764 aa.   1 . . . 762    571/769 (73%)           [WO200157190-A2, 09 AUG. 2001]       AAM79139   Human protein SEQ ID NO 1801 -   259 . . . 1016    434/758 (57%)   0.0             Homo sapiens , 753 aa.   1 . . . 751    565/758 (74%)           [WO200157190-A2, 09 AUG. 2001]                  
 
     [0491] In a BLAST search of public sequence databases, the NOV24a protein was found to have homology to the proteins shown in the BLASTP data in Table 24E.  
               TABLE 24E                          Public BLASTP Results for NOV24a                                         NOV24a   Identities/           Protein       Residues/   Similarities       Accession       Match   for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value               Q96RI6   Unconventional myosin 1G valine   33 . . . 651     616/619 (99%)   0.0           form -  Homo sapiens  (Human), 633   1 . . . 619     617/619 (99%)           aa (fragment).       Q96RI5   Unconventional myosin 1G   33 . . . 651     615/619 (99%)   0.0           methonine form -  Homo sapiens     1 . . . 619     617/619 (99%)           (Human), 633 aa (fragment).       Q63357   Myosin Id (Myosin heavy chain myr   1 . . . 1016   605/1016 (59%)   0.0           4) -  Rattus norvegicus  (Rat), 1006 aa.   1 . . . 1004   781/1016 (76%)       A53933   myosin I myr 4 - rat, 1006 aa.   1 . . . 1016   603/1016 (59%)   0.0               1 . . . 1004   779/1016 (76%)       Q23978   Myosin IA (MIA) (Brush border   8 . . . 1017   501/1018 (49%)   0.0           myosin IA) (BBMIA) -  Drosophila     6 . . . 1007   682/1018 (66%)             melanogaster  (Fruit fly), 1011 aa.                  
 
     [0492] 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               myosin_head   11 . . . 694   308/747 (41%)   1.8e−285               532/747 (71%)                  
 
     Example 25.  
     [0493] The NOV25 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 25A.  
               TABLE 25A                       NOV25 Sequence Analysis                                                SEQ NO:129   1187 bp                     NOV25a,     GGCAGAGTTCCTCTATCTCGTCTTGTTGTGGCAGAGTTCCTCTATCTCGTCTTGTTGCTGATTAAA         CG90474-02       DNA Sequence     GGTGCCCCTGTCTCCAGTTTTTCTCCATCTCCTCGGACGTAGCAGCATC   ATG GTTGGG                   TTCAAGGCCACAGATGTGCCCCCTACTGCCACTGTGAAGTTTCTTAAGGCTGGCACAGCTGCCTGC                   ATCGCAGATCTCATCACCTTTCCTCTGGATACTGCTAAAGTCCGGTTACAGATCCAAGGAGAAAGT                   CAGGGGCCAGTGCGCGCTACAGCCAGCGCCCATCACACCGCGGTACTACCGCTGGACTGTAGCGCG                   CAGTACCGCGGTGTGATGGGCACCATTCTGACCATGGTGCGTACTGAGGGCCCCCGAAGCCTCTAC                   AATGGGCTGGTTGCCGGCCTGCAGCGCCAAATGAGCTTGCCTCTGTCCGCATCGGGCCTGTATGAT                   TCTGTCAAACAGTTCTACACCAAGGGCTCTGAGCATGCCAGCATTGGGAGCCGCCTCCTAGCAGGC                   AGCACCACAGGTGCCCTGGCTGTGGCTGTCGCCCAGCCCACGGATGTGGTAAAGGTCCGATTCCCC                   GCTCAGGCCCGGGCTGGAGGTGGTCGGAGATACCAAAGCACCGTCAATGCCTACAAGACCATTGCC                   CGAGAGGAAGGGTTCCGGGGCCTCTGGAAAGGGACCTCTCCCAATGTTGCTCGTAATGCCATTGTC                   AACTGTGCTGAGCTGGTGACCTATGACCTCATCATCAAGGATGCTCTGAAAGCCAACCTCATGACA                   GATGACCTCCCTTGCCACTTCACTTCTGCCTTTGGGCAGGCTTCTGAAACCACTGTCATCGCCTCC                   CCTGTAGACGTGGTCAAGACGAGATACATGAACTCTGCCCTGGGCCAGTACAGTAGCGCTGGCCAC                   TGTGCCCTTACCATGCTCCAGAAGGAGGGGCCCCGAGCCTTCTACAAAGGGTTCATGCCCTCCTTT                   CTCCGCTTGGGTTCCTGGAACGTGGTGATGTTCGTCACCTATGAGCAGCTGAAACGAGCCCTCATG                   GCTGCCTGCACTTCCCGAGAGGCTCCCTTC TGA   GCCTCTCCTGCTGCTGACCTGATCACCTCTAAC                       TTTGTCTCTAGCCGGCGCCATGCTTTCCTTTTCTTCCTTCTTTCTCTTCCCTCCTTCCCTTCTCTC                                           ORF Start: ATG at 124       ORF Stop: TGA at 1087           SEQ ID NO:130   321 aa   MW at 34334.3 kD                     NOV25a,   MVGFKATDVPPTATVKFLGAGTAACIADLITFPLDTAKVRLQIQGESQGPVRATASAHHTAVLGAG       CG90474-02       Protein Sequence   CSAQYRGVMGTILTMRTEGPRSLYNGLVAGLQRQMSFASVRIGLYDSVKQGFYTKGSEHASIGSRL                   LAGSTTGALAVAVAQPTDVVKVRFQAQARAGGGRRYQSTVNAYKTIAREEGFRGLWKGTSPNVARN                   AIVNCAELVTYDLIKDALLKANLMTDDLPCHFTSAFGAGFCTTVIASPVDVVKTRYMNSALGQYSS                   AGHCALTMLQKEGPRAFYKGFMPSFLRLGSWNVVMFVTYEQLKRALMAACTSREAPF                                     SEQ ID NO:131   960 bp                     NOV25b,     AGGAAATCAGCATC   ATG GTTGGGTTCAAGGCCACAGATGTGCCCCCTACTGCCACTGTGAAGTTTC       CG90474-01       DNA Sequence   TTGGGGCTGGCACAGCTGCCTGCATCGCAGATCTCATCACCTTTCCTCTGGATACTGCTAAAGTCC                   GGTTACAGATCCAAGGAGAAAGTCAGGGGCCAGTGCGCGCTACAGCCAGCGCCCAGTACCGCGGTG                   TGATGGGCACCATTCTGACCATGGTGCGTACTGAGGGCCCCCGAAGCCTCTACAATGGGCTGGTTG                   CCGGCCTGCAGCGCCAAATGAGCTTTGCCTCTGTCCGCATCGGCCTGTATGATTCTGTCAGGCAGT                   TCTACACCAAGGGCTCTGAGCATGCCAGCATTGGGAGCCGCCTCCTAGAAGGCAGCACCACAGGTG                   CCTGGCTGTGGCTGTGGCCCAGCCCACGGATGTGGTAAAGGTCCGATTCCAAGCTCAGGCCCGGGG                   CTGGAGGTGGTCGGAGATACCAAAGCACCGTCAATGCCTACAAGACCATTGCCCGAGAGGAAGGGT                   TCCGGGGCCTCTGGAAAGGGACCTCTCCCAATGTTGCTCGTAATGCCATTGTCAACTGTGCTGAGC                   TGGTGACCTATGACCTCATCAAGGATGCCCTCCTGAAAGCCAACCTCATGACAGATGACCTCCCTT                   GCCACTTCACTTCTGCCTTTGGGGCAGGCTTCTGCACCACTGTCATCGCCTCCCCTGTACACGTGG                   TCAAGACGAGATACATGAACTCTGCCCTGGGCCAGTACAGTAGCGCTGGCCACTGTGCCCTTACCA                   TGCTCCAGAAGGAOGGCCCCGAGCCTTCTACAAAGGGTTCATGCCCTCCTTTCTCCGCTTGAAATT                   CCTGGAACGTGGTGATGTTCGTCACCTATGAGCAGCTGAAACGAGCCCTCATGGCTGCCTGCACTT                   CCCGAGAGGCTCCCTTC TGA   GCCTCTCCTCCTGCTG                                           ORF Start: ATG at 15       ORF Stop: TGA at 942           SEQ ID NO:132   309 aa   MW at 33229.0 kD                     NOV25b,   MVGFKATDVPPTATVKFLGAGTAACIADLITFPLDTAKVRLQIQGESQGPVRATASAQYRGVMGTI       CG90474-01       Protein Sequence   LTMVRTEGPRSLYNGLVAGLQRQMSFASVRIGLYDSVKQFYTKGSEHASISGSRLLAGTTGALAVA                   VAQPTDVVKVRFQAQARAGGGRRYQSTVNAYKTIAREEGFGLWKGTSPNVARNAIVNCAELTVTYD                   LIKDALLKANLMTDDLPCHFTSAFGAGFCTTVIASPVDVVKTRYMNSALGQYSSAGHCALTMLQKE                   IGPRAFYKGFMPSFLRLGSWNVVMFVTYEQLKRALMAACTSREAPF                  
 
     [0494] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 25B.  
               TABLE 25B                          Comparison of NOV25a against NOV25b.                                 Protein   NOV25a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV25b   1 . . . 321   309/321 (96%)               1 . . . 309   309/321 (96%)                      
 
     [0495] Further analysis of the NOV25a protein yielded the following properties shown in Table 25C.  
               TABLE 25C                       Protein Sequence Properties NOV25a                                        SignalP   No Known Signal Sequence Predicted       analysis:       PSORT II   PSG: a new signal peptide prediction method       analysis:   N-region: length 8; pos. chg 1; neg. chg 1           H-region: length 7; peak value 0.01           PSG score: −4.39           GvH: von Heijne&#39;s method for signal seq. recognition           GvH score (threshold: −2.1): −7.32           possible cleavage site: between 27 and 28           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation           Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 0.69 (at 18)           ALOM score: 0.69 (number of TMSs: 0)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   0   Hyd Moment(75):   5.13           Hyd Moment(95):   6.71   G content:   3           D/E content:   2   S/T content:   4                         Score: −7.33           Gavel: prediction of cleavage sites for mitochondrial preseq           cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals           pat4: none           pat7: none           bipartite: none           content of basic residues: 10.6%           NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2 : 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:           type 1: none           type 2: none           NMYR: N-myristoylation pattern : none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination           Prediction: cytoplasmic           Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions           total: 0 residues           Final Results (k = 9/23):           47.8%: cytoplasmic           26.1%: mitochondrial           26.1%: nuclear           &gt;&gt; prediction for CG90474-02 is cyt (k = 23)                  
 
     [0496] 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 25D.  
               TABLE 25D                          Geneseq Results for NOV25a                                         NOV25a   Identities/                   Residues/   Similarities       Geneseq   Protein/Organism/Length [Patent   Match   for the   Expect       Identifier   #, Date]   Residues   Matched Region   Value               AAY72342   Human uncoupling protein, UCP-2 -   1 . . . 321   309/321 (96%)   e−174             Homo sapiens , 309 aa.   1 . . . 309   309/321 (96%)           [WO200078941-A2, 28 DEC. 2000]       AAU09077   Human uncoupling protein, UCP-2 -   1 . . . 321   309/321 (96%)   e−174             Homo sapiens , 314 aa.   6 . . . 314   309/321 (96%)           [WO200175131-A2, 11 OCT. 2001]       AAY44292   Human uncoupling protein-2 -  Homo     1 . . . 321   309/321 (96%)   e−174             sapiens , 309 aa. [WO9953953-A2,   1 . . . 309   309/321 (96%)           28 OCT. 1999]       AAY45002   Tularik human uncoupling protein-2 -   1 . . . 321   309/321 (96%)   e−174             Homo sapiens , 309 aa.   1 . . . 309   309/321 (96%)           [WO200006087-A2, 10 FEB. 2000]       AAY28351   UCP2 amino acid sequence -  Homo     1 . . . 321   309/321 (96%)   e−174             sapiens , 309 aa. [WO9937812-A1,   1 . . . 309   309/321 (96%)           29 JUL. 1999]                  
 
     [0497] In a BLAST search of public sequence databases, the NOV25a protein was found to have homology to the proteins shown in the BLASTP data in Table 25E.  
               TABLE 25E                          Public BLASTP Results for NOV25a                                         NOV25a   Identities/           Protein       Residues/   Similarities       Accession       Match   for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value               P55851   Mitochondrial uncoupling protein 2   1 . . . 321   309/321 (96%)   e−173           (UCP 2) (UCPH) -  Homo sapiens     1 . . . 309   309/321 (96%)           (Human), 309 aa.       Q9N2J1   Mitochondrial uncoupling protein 2   1 . . . 321   301/321 (93%)   e−168           (UCP 2) -  Canis familiaris  (Dog), 309   1 . . . 309   304/321 (93%)           aa.       Q9R246   Uncoupling protein 2 -  Mus musculus     1 . . . 321   298/321 (92%)   e−166           (Mouse), 309 aa.   1 . . . 309   300/321 (92%)       P70406   Mitochondrial uncoupling protein 2   1 . . . 321   297/321 (92%)   e−165           (UCP 2) (UCPH) -  Mus musculus     1 . . . 309   299/321 (92%)           (Mouse), 309 aa.       Q9ER17   Uncoupling protein 2 -  Phodopus     1 . . . 321   294/321 (91%)   e−164             sungorus  (Striped hairy-footed   1 . . . 309   298/321 (92%)           hamster) (Djungarian hamster), 309           aa.                  
 
     [0498] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25F.  
               TABLE 25F                          Domain Analysis of NOV25a                                 NOV25a   Identities/Similarities   Expect       Pfam Domain   Match Region   for the Matched Region   Value               mito_carr    12 . . . 125   34/127 (27%)   2.6e−28               94/127 (74%)       mito_carr   127 . . . 222   39/125 (31%)   1.7e−30               83/125 (66%)       mito_carr   225 . . . 316   27/125 (22%)   3.1e−26               73/125 (58%)                  
 
     Example B  
     Sequencing Methodology and Identification of NOVX Clones  
     [0499] 1. GeneCalling™ Technology: This is a proprietary method of performing differential gene expression profiling between two or more samples developed at CuraGen and described by Shimkets, et al., “Gene expression analysis by transcript profiling coupled to a gene database query” Nature Biotechnology 17:198-803 (1999). cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then digested with up to as many as 120 pairs of restriction enzymes and pairs of linker-adaptors specific for each pair of restriction enzymes were ligated to the appropriate end. The restriction digestion generates a mixture of unique cDNA gene fragments. Limited PCR amplification is performed with primers homologous to the linker adapter sequence where one primer is biotinylated and the other is fluorescently labeled. The doubly labeled material is isolated and the fluorescently labeled single strand is resolved by capillary gel electrophoresis. A computer algorithm compares the electropherograms from an experimental and control group for each of the restriction digestions. This and additional sequence-derived information is used to predict the identity of each differentially expressed gene fragment using a variety of genetic databases. The identity of the gene fragment is confirmed by additional, gene-specific competitive PCR or by isolation and sequencing of the gene fragment.  
     [0500] 2. SeqCalling™ Technology: cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then sequenced using CuraGen&#39;s proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation&#39;s database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.  
     [0501] 3. PathCalling™ Technology: The NOVX nucleic acid sequences are derived by laboratory screening of cDNA library by the two-hybrid approach. cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, are sequenced. In silico prediction was based on sequences available in CuraGen Corporation&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
     [0502] The laboratory screening was performed using the methods summarized below:  
     [0503] cDNA libraries were derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then directionally cloned into the appropriate two-hybrid vector (Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, Calif.) were then transferred from  E. coli  into a CuraGen Corporation proprietary yeast strain (disclosed in U.S. Pat. Nos. 6,057,101 and 6,083,693, incorporated herein by reference in their entireties).  
     [0504] Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corportion proprietary library of human sequences was used to screen multiple Gal4-AD fusion cDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Gal4-AD fusion contains an individual cDNA. Each sample was amplified using the polymerase chain reaction (PCR) using non-specific primers at the cDNA insert boundaries. Such PCR product was sequenced; sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation&#39;s database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.  
     [0505] Physical clone: the cDNA fragment derived by the screening procedure, covering the entire open reading frame is, as a recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library. The recombinant plasmid is inserted into the host and selected by the yeast hybrid diploid generated during the screening procedure by the mating of both CuraGen Corporation proprietary yeast strains N106′ and YULH (U.S. Pat. Nos. 6,057,101 and 6,083,693).  
     [0506] 4. RACE: Techniques based on the polymerase chain reaction such as rapid amplification of cDNA ends (RACE), were used to isolate or complete the sequence of the cDNA of the invention. Usually multiple clones were sequenced from one or more human samples to derive the sequences for fragments. Various human tissue samples from different donors were used for the RACE reaction. The sequences derived from these procedures were included in the SeqCalling Assembly process described in preceding paragraphs.  
     [0507] 5. Exon Linking: The NOVX target sequences identified in the present invention were subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain-amygdala, brain-cerebellum, brain-hippocampus, brain-substantia nigra, brain-thalamus, brain-whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma-Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus. Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation&#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.  
     [0508] 6. Physical Clone: Exons were predicted by homology and the intron/exon boundaries were determined using standard genetic rules. Exons were further selected and refined by means of similarity determination using multiple BLAST (for example, tBlastN, BlastX, and BlastN) searches, and, in some instances, GeneScan and Grail. Expressed sequences from both public and proprietary databases were also added when available to further define and complete the gene sequence. The DNA sequence was then manually corrected for apparent inconsistencies thereby obtaining the sequences encoding the full-length protein.  
     [0509] The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening purposes.  
     Example C  
     Quantitative Expression Analysis of Clones in Various Cells and Tissues  
     [0510] 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/51 (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).  
     [0511] 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 2.5:128s: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.  
     [0512] 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.  
     [0513] 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.  
     [0514] 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.  
     [0515] 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.  
     [0516] 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.  
     [0517] Panels 1, 1.1, 1.2, and 1.3D  
     [0518] 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.  
     [0519] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:  
     [0520] ca.=carcinoma,  
     [0521] *=established from metastasis,  
     [0522] met=metastasis,  
     [0523] s cell var=small cell variant,  
     [0524] non-s=non-sm=non-small,  
     [0525] squam=squamous,  
     [0526] pl. eff=pl effusion=pleural effusion,  
     [0527] glio=glioma,  
     [0528] astro=astrocytoma, and  
     [0529] neuro=neuroblastoma.  
     [0530] General_screening_panel_v1.4, v1.5, v1.6 and 1.7  
     [0531] The plates for Panels 1.4, 1.5, 1.6 and 1.7 include 2 control wells (genomic DNA control and chemistry control) and 88 to 94 wells containing cDNA from various samples. The samples in Panels 1.4, 1.5, 1.6 and 1.7 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, 1.6 and 1.7 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, 1.6 and 1.7 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.  
     [0532] Panels 2D, 2.2, 2.3 and 2.4  
     [0533] 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.  
     [0534] HASS Panel v 1.0  
     [0535] 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.  
     [0536] ARDAIS Panel v 1.0  
     [0537] The plates for ARDAIS panel v 1.0 generally include 2 control wells and 22 test samples composed of RNA isolated from human tissue procured by surgeons working in close cooperation with Ardais Corporation. The tissues are derived from human lung malignancies (lung adenocarcinoma or lung squamous cell carcinoma) and in cases where indicated many malignant samples have “matched margins” obtained from noncancerous lung tissue just adjacent to the tumor. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue) in the results below. The tumor tissue and the “matched margins” are evaluated by independent pathologists (the surgical pathologists and again by a pathologist at Ardais). Unmatched malignant and non-malignant RNA samples from lungs were also obtained from Ardais. Additional information from Ardais provides a gross histopathological assessment of tumor differentiation grade and stage. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical state of the patient.  
     [0538] Panel 3D, 3.1 and 3.2  
     [0539] The plates of Panel 3D, 3.1, and 3.2 are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines, 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma of the tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D, 3.1, 3.2, 1, 1.1., 1.2, 1.3D, 1.4, 1.5, and 1.6 are of the most common cell lines used in the scientific literature.  
     [0540] Panels 4D, 4R, and 4.1D  
     [0541] 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.).  
     [0542] 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.  
     [0543] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2×10 6 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10 −5 M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.  
     [0544] Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer&#39;s instructions. Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, Utah), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 1001, M 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 10 ng/ml. Dendritic cells were also stimulated with anti-CD40 monoclonal antibody (Pharmingen) at 10 μg/ml for 6 and 12-14 hours.  
     [0545] 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 0.51 g/ml anti-CD28 (Pharmingen) and 3ug/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the cells were harvested for RNA preparation. To prepare chronically activated CD8 lymphocytes, we activated the isolated CD8 lymphocytes for 4 days on anti-CD28 and anti-CD3 coated plates and then harvested the cells and expanded them in DMEM 5% FCS (Hyclone), 110 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.  
     [0546] 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), I OOIM non essential amino acids (Gibco), IrrM sodium pyruvate (Gibco), mercaptoethanol 5.5xlO-5M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 1 Ogg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24,48 and 72 hours.  
     [0547] To prepare the primary and secondary Th1/Th2 and Trl 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.  
     [0548] 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), 100CM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco). CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.  
     [0549] For these cell lines and blood cells, RNA was prepared by lysing approximately 10 7 cells/ml using Trizol (Gibco BRL). Briefly, {fraction (1/10)} volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 5 μl DTT, 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with {fraction (1/10)} volume of 3M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at −80° C.  
     [0550] AI_comprehensive Panel_v1.0  
     [0551] 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.  
     [0552] 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.  
     [0553] 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.  
     [0554] 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.  
     [0555] Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD was purchased from Clinomics. Emphysema patients ranged in age from 40-70 and all were smokers, this age range was chosen to focus on patients with cigarette-linked emphysema and to avoid those patients with alpha-1 anti-trypsin deficiencies. Asthma patients ranged in age from 36-75, and excluded smokers to prevent those patients that could also have COPD. COPD patients ranged in age from 35-80 and included both smokers and non-smokers. Most patients were taking corticosteroids, and bronchodilators.  
     [0556] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:  
     [0557] AI=Autoimmunity  
     [0558] Syn=Synovial  
     [0559] Normal=No apparent disease  
     [0560] Rep22/Rep20=individual patients  
     [0561] RA=Rheumatoid arthritis  
     [0562] Backus=From Backus Hospital  
     [0563] OA=Osteoarthritis  
     [0564] (SS) (BA) (MF)=Individual patients  
     [0565] Adj=Adjacent tissue  
     [0566] Match control=adjacent tissues  
     [0567] -M=Male  
     [0568] -F=Female  
     [0569] COPD=Chronic obstructive pulmonary disease  
     [0570] AI.05 Chondrosarcoma  
     [0571] The AI.05 chondrosarcoma plates are comprised of SW1353 cells that had been subjected to serum starvation and treatment with cytokines that are known to induce MMP (1, 3 and 13) synthesis (eg. IL1beta). These treatments include: IL-1beta (10 ng/ml), IL-1beta+TNF-alpha (50 ng/ml), IL-1beta+Oncostatin (50 ng/ml) and PMA (100 ng/ml). The SW1353 cells were obtained from the ATCC (American Type Culture Collection) and were all cultured under standard recommended conditions. The SW1353 cells were plated at 3×10 5  cells/ml (in DMEM medium-10% FBS) in 6-well plates. The treatment was done in triplicate, for 6 and 18 h. The supernatants were collected for analysis of MMP 1, 3 and 13 production and for RNA extraction. RNA was prepared from these samples using the standard procedures.  
     [0572] Panels 5D and 5I  
     [0573] 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.  
     [0574] 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:  
     [0575] Patient 2: Diabetic Hispanic, overweight, not on insulin  
     [0576] Patient 7-9: Nondiabetic Caucasian and obese (BMI&gt;30)  
     [0577] Patient 10: Diabetic Hispanic, overweight, on insulin  
     [0578] Patient 11: Nondiabetic African American and overweight  
     [0579] Patient 12: Diabetic Hispanic on insulin  
     [0580] Adiocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/Bio Whittaker) 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:  
     [0581] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose  
     [0582] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated  
     [0583] Donor 2 and 3 AD: Adipose, Adipose Differentiated  
     [0584] 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.  
     [0585] 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.  
     [0586] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:  
     [0587] GO Adipose=Greater Omentum Adipose  
     [0588] SK=Skeletal Muscle  
     [0589] UT=Uterus  
     [0590] PL=Placenta  
     [0591] AD=Adipose Differentiated  
     [0592] AM=Adipose Midway Differentiated  
     [0593] U=Undifferentiated Stem Cells  
     [0594] Panel CNSD.01  
     [0595] 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.  
     [0596] 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.  
     [0597] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:  
     [0598] PSP=Progressive supranuclear palsy  
     [0599] Sub Nigra=Substantia nigra  
     [0600] Glob Palladus=Globus palladus  
     [0601] Temp Pole=Temporal pole  
     [0602] Cing Gyr=Cingulate gyrus  
     [0603] BA 4=Brodman Area 4  
     [0604] Panel CNS_Neurodegeneration_V1.0  
     [0605] 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.  
     [0606] Disease diagnoses are taken from patient records. The panel contains six brains from Alzheimer&#39;s disease (AD) patients, and eight brains from “Normal controls” who showed no evidence of dementia prior to death. The eight normal control brains are divided into two categories: Controls with no dementia and no Alzheimer&#39;s like pathology (Controls) and controls with no dementia but evidence of severe Alzheimer&#39;s like pathology, (specifically senile plaque load rated as level 3 on a scale of 0-3; 0=no evidence of plaques, 3=severe AD senile plaque load). Within each of these brains, the following regions are represented: hippocampus, temporal cortex (Brodman Area 21), parietal cortex (Brodman area 7), and occipital cortex (Brodman area 17). These regions were chosen to encompass all levels of neurodegeneration in AD. The hippocampus is a region of early and severe neuronal loss in AD; the temporal cortex is known to show neurodegeneration in AD after the hippocampus; the parietal cortex shows moderate neuronal death in the late stages of the disease; the occipital cortex is spared in AD and therefore acts as a “control” region within AD patients. Not all brain regions are represented in all cases.  
     [0607] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:  
     [0608] AD=Alzheimer&#39;s disease brain; patient was demented and showed AD-like pathology upon autopsy  
     [0609] Control=Control brains; patient not demented, showing no neuropathology  
     [0610] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology  
     [0611] SupTemporal Ctx=Superior Temporal Cortex  
     [0612] Inf Temporal Ctx=Inferior Temporal Cortex  
     [0613] A. CG125312-01 (NOV6a): Similar to Myosin IF (Myosin IE).  
     [0614] Expression of gene CG125312-01 was assessed using the primer-probe set Ag7882, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB, AC and AD.  
               TABLE AA                          Probe Name Ag7882                                             Start   SEQ ID       Primers   Sequences   Length   Positions   No                                         Forward   5′-cagaccaqtgagcagttcct-3′   20   1721   133               Probe   TET-5′-ccccttcttgtctccatccagctt-3′-TAMRA   24   1760   134               Reverse   5′-cttgtttcttgatcttqgagcc-3′   22   1799   135                  
 
     [0615]               TABLE AB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)               Ag7882, Run           Tissue Name   316264628                                         AD 1 Hippo   7.0           AD 2 Hippo   6.9           AD 3 Hippo   8.0           AD 4 Hippo   0.0           AD 5 Hippo   5.1           AD 6 Hippo   10.3           Control 2 Hippo   0.0           Control 4 Hippo   17.7           Control (Path) 3 Hippo   0.0           AD 1 Temporal Ctx   2.4           AD 2 Temporal Ctx   6.7           AD 3 Temporal Ctx   0.0           AD 4 Temporal Ctx   0.0           AD 5 Inf Temporal Ctx   6.6           AD 5 Sup Temporal Ctx   6.5           AD 6 Inf Temporal Ctx   100.0           AD 6 Sup Temporal Ctx   62.0           Control 1 Temporal Ctx   0.0           Control 2 Temporal Ctx   38.4           Control 3 Temporal Ctx   0.0           Control 3 Temporal Ctx   1.8           Control (Path) 1 Temporal Ctx   0.0           Control (Path) 2 Temporal Ctx   0.0           Control (Path) 3 Temporal Ctx   0.0           Control (Path) 4 Temporal Ctx   7.5           AD 1 Occipital Ctx   0.0           AD 2 Occipital Ctx (Missing)   0.0           AD 3 Occipital Ctx   2.3           AD 4 Occipital Ctx   0.0           AD 5 Occipital Ctx   9.0           AD 6 Occipital Ctx   2.0           Control 1 Occipital Ctx   15.0           Control 2 Occipital Ctx   13.9           Control 3 Occipital Ctx   11.9           Control 4 Occipital Ctx   0.0           Control (Path) 1 Occipital Ctx   18.2           Control (Path) 2 Occipital Ctx   0.0           Control (Path) 3 Occipital Ctx   2.3           Control (Path) 4 Occipital Ctx   0.0           Control 1 Parietal Ctx   38.2           Control 2 Parietal Ctx   15.5           Control 3 Parietal Ctx   0.0           Control (Path) 1 Parietal Ctx   16.5           Control (Path) 2 Parietal Ctx   1.1           Control (Path) 3 Parietal Ctx   0.0           Control (Path) 4 Parietal Ctx   11.7                        
     [0616]               TABLE AC                          General_screening_panel_v1.7                                 Rel. Exp. (%)               Ag7882, Run           Tissue Name   319066291                                         Adipose   0.1           HUVEC   0.0           Melanoma* Hs688(A).T   0.0           Melanoma* Hs688(B).T   0.0           Melanoma (met) SK-MEL-5   100.0           Testis   0.0           Prostate ca. (bone met) PC-3   0.0           Prostate ca. DU145   0.0           Prostate pool   0.0           Uterus pool   0.0           Ovarian ca. OVCAR-3   0.0           Ovarian ca. (ascites) SK-OV-3   0.0           Ovarian ca. OVCAR-4   0.0           Ovarian ca. OVCAR-5   0.0           Ovarian ca. IGROV-1   0.0           Ovarian ca. OVCAR-8   0.0           Ovary   0.0           Breast ca. MCF-7   0.0           Breast ca. MDA-MB-231   0.0           Breast ca. BT-549   0.0           Breast ca. T47D   0.0           Breast pool   0.0           Trachea   0.0           Lung   0.3           Fetal Lung   0.2           Lung ca. NCI-N417   0.0           Lung ca. LX-1   0.0           Lung ca. NCI-H146   0.0           Lung ca. SHP-77   0.0           Lung ca. NCI-H23   0.0           Lung ca. NCI-H460   0.0           Lung ca. HOP-62   0.0           Lung ca. NCI-H522   0.0           Lung ca. DMS-114   0.0           Liver   0.0           Fetal Liver   0.1           Kidney pool   0.1           Fetal Kidney   0.0           Renal ca. 786-0   0.0           Renal ca. A498   0.0           Renal ca. ACHN   0.0           Renal ca. UO-31   0.0           Renal ca. TK-10   0.0           Bladder   0.1           Gastric ca. (liver met.) NCI-N87   0.0           Stomach   0.0           Colon ca. SW-948   0.0           Colon ca. SW480   0.0           Colon ca. (SW480 met) SW620   0.0           Colon ca. HT29   0.0           Colon ca. HCT-116   0.0           Colon cancer tissue   0.0           Colon ca. SW1116   0.0           Colon ca. Colo-205   0.0           Colon ca. SW-48   0.0           Colon   0.1           Small Intestine   0.0           Fetal Heart   0.0           Heart   0.0           Lymph Node pool 1   0.0           Lymph Node pool 2   0.4           Fetal Skeletal Muscle   0.0           Skeletal Muscle pool   0.0           Skeletal Muscle   0.0           Spleen   0.2           Thymus   0.0           CNS cancer (glio/astro) SF-268   0.0           CNS cancer (glio/astro) T98G   0.0           CNS cancer (neuro; met) SK-N-AS   0.0           CNS cancer (astro) SF-539   0.0           CNS cancer (astro) SNB-75   0.0           CNS cancer (glio) SNB-19   0.0           CNS cancer (glio) SF-295   0.0           Brain (Amygdala)   0.0           Brain (Cerebellum)   0.0           Brain (Fetal)   0.0           Brain (Hippocampus)   0.0           Cerebral Cortex pool   0.0           Brain (Substantia nigra)   0.0           Brain (Thalamus)   0.0           Brain (Whole)   0.1           Spinal Cord   0.0           Adrenal Gland   0.0           Pituitary Gland   0.0           Salivary Gland   0.0           Thyroid   0.1           Pancreatic ca. PANC-1   0.0           Pancreas pool   0.0                        
     [0617]               TABLE AD                          Panel 4.1D                         Rel. Exp. (%)           Ag7882, Run       Tissue Name   316264536                             Secondary Th1 act   6.9       Secondary Th2 act   4.7       Secondary Tr1 act   1.0       Secondary Th1 rest   3.8       Secondary Th2 rest   2.6       Secondary Tr1 rest   6.3       Primary Th1 act   0.0       Primary Th2 act   2.3       Primary Tr1 act   0.5       Primary Th1 rest   0.8       Primary Th2 rest   2.7       Primary Tr1 rest   0.3       CD45RA CD4 lymphocyte act   0.0       CD45RO CD4 lymphocyte act   4.4       CD8 lymphocyte act   2.5       Secondary CD8 lymphocyte rest   0.0       Secondary CD8 lymphocyte act   3.0       CD4 lymphocyte none   3.6       2ry Th1/Th2/Tr1_anti-CD95 CH11   9.9       LAK cells rest   11.0       LAK cells IL-2   5.9       LAK cells IL-2 + IL-12   0.0       LAK cells IL-2 + IFN gamma   1.7       LAK cells IL-2 + IL-18   1.7       LAK cells PMA/ionomycin   8.4       NK Cells IL-2 rest   18.0       Two Way MLR 3 day   8.8       Two Way MLR 5 day   2.1       Two Way MLR 7 day       PBMC rest   4.5       PBMC PWM   0.9       PBMC PHA-L   0.6       Ramos (B cell) none   0.0       Ramos (B cell) ionomycin   0.0       B lymphocytes PWM       B lymphocytes CD40L and IL-4   0.2       EOL-1 dbcAMP   17.2       EOL-1 dbcAMP PMA/ionomycin   5.9       Dendritic cells none   12.6       Dendritic cells LPS   2.3       Dendritic cells anti-CD40   6.1       Monocytes rest   12.1       Monocytes LPS   13.0       Macrophages rest   2.4       Macrophages LPS   1.9       HUVEC none   0.0       HUVEC starved   0.0       HUVEC IL-1beta   0.0       HUVEC IFN gamma   0.0       HUVEC TNF alpha + IFN gamma   0.0       HUVEC TNF alpha + IL4   0.0       HUVEC IL-11   0.0       Lung Microvascular EC none   0.0       Lung Microvascular EC TNFalpha + IL-1beta   0.0       Microvascular Dermal EC none   0.0       Microsvasular Dermal EC TNFalpha + IL-1beta   0.0       Bronchial epithelium TNFalpha + IL1beta   0.0       Small airway epithelium none   0.0       Small airway epithelium TNFalpha + IL-1beta   0.0       Coronery artery SMC rest   0.0       Coronery artery SMC TNFalpha + IL-1beta   0.0       Astrocytes rest   0.0       Astrocytes TNFalpha + IL-1beta   0.0       KU-812 (Basophil) rest   0.0       KU-812 (Basophil) PMA/ionomycin   0.3       CCD1106 (Keratinocytes) none   0.0       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   0.0       Liver cirrhosis   0.0       NCI-H292 none   0.0       NCI-H292 IL-4   0.0       NCI-H292 IL-9   0.0       NCI-H292 IL-13   0.0       NCI-H292 IFN gamma   0.0       HPAEC none   0.0       HPAEC TNF alpha + IL-1 beta   0.0       Lung fibroblast none   0.0       Lung fibroblast TNF alpha + IL-1 beta   0.0       Lung fibroblast IL-4   0.0       Lung fibroblast IL-9   0.0       Lung fibroblast IL-13   0.0       Lung fibroblast IFN gamma   0.0       Dermal fibroblast CCD1070 rest   0.0       Dermal fibroblast CCD1070 TNF alpha   32.3       Dermal fibroblast CCD1070 IL-1 beta   0.0       Dermal fibroblast IFN gamma   0.0       Dermal fibroblast IL-4   0.0       Dermal Fibroblasts rest   0.0       Neutrophils TNFa + LPS   30.8       Neutrophils rest   100.0       Colon   0.0       Lung   0.7       Thymus   1.3       Kidney   0.1                    
     [0618] CNS_neurodegeneration_v1.0 Summary: Ag7882 Low expression of this gene is seen in temporal cortex of an Alzheimer&#39;s patient. Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of Alzheimer&#39;s diseases.  
     [0619] General_screening_panel_v1.7 Summary: Ag7882 High expression of this gene is seen exclusively in a melanoma SK-MEL-5 cell line (CT=26). Therefore, expression of this gene may be used as diagnostic marker to detect presence of melanoma and therapeutic modulation of this gene or its protein product may be useful in the treatment of melanoma.  
     [0620] Panel 4.1D Summary: Ag7882 Highest expression of this gene is detected in resting neutrophils (CT=29.7). Significant but reduced expression of this gene is also seen in activated neutrophils. In addition, moderate to low expression of this gene is also seen in secondary polarized T cells, memory T cells, LAK cells, resting IL-2 treated NK cells, resting PBMC cells, eosinophils, dendritic cell, monocytes and activated dermal fibroblasts. Therefore, the gene product may reduce activation of these inflammatory cells and be useful as a protein therapeutic to reduce or eliminate the symptoms in patients with Crohii&#39;s disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis. In addition, small molecule or antibody antagonists of this gene product may be effective in increasing the immune response in patients with AIDS or other immunodeficiencies.  
     [0621] B. CG134632-01: dUTPase (Mitochondrial Form).  
     [0622] Expression of gene CG134632-01 was assessed using the primer-probe set Ag6505, described in Table BA. Results of the RTQ-PCR runs are shown in Tables BB, BC and BD.  
               TABLE BA                          Probe Name Ag6505                                             Start   SEQ ID       Primers   Sequences   Length   Positions   No                                         Forward   5′-tgctaccatttccttacgtctct-3′   23   442   136               Probe   TET-5′-cttcgctcagcgatgcaaaacgc-3′-TAMRA   23   466   137               Reverse   5′-cctggcccggagagtac-3′17   520   138                  
 
     [0623]               TABLE BB                          General_screening_panel_v1.6                                 Rel. Exp. (%)               Ag6505, Run           Tissue Name   277252458                                         Adipose   1.1           Melanoma* Hs688(A).T   15.2           Melanoma* Hs688(B).T   12.8           Melanoma* M14   43.8           Melanoma* LOXIMVI   7.3           Melanoma* SK-MEL-5   3.5           Squamous cell carcinoma SCC-4   4.9           Testis Pool   3.7           Prostate ca.* (bone met) PC-3   5.0           Prostate Pool   4.7           Placenta   5.1           Uterus Pool   3.7           Ovarian ca. OVCAR-3   36.6           Ovarian ca. SK-OV-3   36.6           Ovarian ca. OVCAR-4   7.2           Ovarian ca. OVCAR-5   54.7           Ovarian ca. IGROV-1   34.2           Ovarian ca. OVCAR-8   100.0           Ovary   10.1           Breast ca. MCF-7   6.8           Breast ca. MDA-MB-231   15.2           Breast ca. BT 549   6.5           Breast ca. T47D   5.3           Breast ca. MDA-N   35.8           Breast Pool   13.0           Trachea   6.3           Lung   0.8           Fetal Lung   9.2           Lung ca. NCI-N417   12.4           Lung ca. LX-1   15.9           Lung ca. NCI-H146   9.7           Lung ca. SHP-77   10.1           Lung ca. A549   14.4           Lung ca. NCI-H526   7.6           Lung ca. NCI-H23   7.6           Lung ca. NCI-H460   12.6           Lung ca. HOP-62   5.2           Lung ca. NCI-H522   8.9           Liver   0.5           Fetal Liver   4.5           Liver ca. HepG2   4.3           Kidney Pool   19.2           Fetal Kidney   7.9           Renal ca. 786-0   8.9           Renal ca. A498   5.8           Renal ca. ACHN   9.7           Renal ca. UO-31   9.2           Renal ca. TK-10   11.0           Bladder   4.0           Gastric ca. (liver met.) NCI-N87   19.9           Gastric ca. KATO III   7.7           Colon ca. SW-948   2.8           Colon ca. SW480   25.0           Colon ca.* (SW480 met) SW620   12.1           Colon ca. HT29   9.5           Colon ca. HCT-116   7.9           Colon ca. CaCo-2   3.8           Colon cancer tissue   12.0           Colon ca. SW1116   5.9           Colon ca. Colo-205   11.9           Colon ca. SW-48   1.8           Colon Pool   10.3           Small Intestine Pool   8.8           Stomach Pool   5.1           Bone Marrow Pool   3.5           Fetal Heart   6.2           Heart Pool   7.2           Lymph Node Pool   13.8           Fetal Skeletal Muscle   3.1           Skeletal Muscle Pool   1.0           Spleen Pool   8.6           Thymus Pool   11.0           CNS cancer (glio/astro) U87-MG   41.2           CNS cancer (glio/astro) U-118-MG   24.8           CNS cancer (neuro; met) SK-N-AS   15.9           CNS cancer (astro) SF-539   13.6           CNS cancer (astro) SNB-75   38.2           CNS cancer (glio) SNB-19   38.2           CNS cancer (glio) SF-295   12.9           Brain (Amygdala) Pool   9.8           Brain (cerebellum)   12.9           Brain (fetal)   9.9           Brain (Hippocampus) Pool   8.1           Cerebral Cortex Pool   7.0           Brain (Substantia nigra) Pool   13.9           Brain (Thalamus) Pool   15.0           Brain (whole)   7.1           Spinal Cord Pool   10.6           Adrenal Gland   7.7           Pituitary gland Pool   4.7           Salivary Gland   4.2           Thyroid (female)   12.7           Pancreatic ca. CAPAN2   10.0           Pancreas Pool   6.7                        
     [0624]               TABLE BC                          Panel 4.1D                         Rel. Exp. (%)           Ag6505, Run       Tissue Name   271410126                             Secondary Th1 act   52.5       Secondary Th2 act   76.3       Secondary Tr1 act   34.4       Secondary Th1 rest   14.5       Secondary Th2 rest   11.8       Secondary Tr1 rest   8.5       Primary Th1 act   23.2       Primary Th2 act   80.1       Primary Tr1 act   85.3       Primary Th1 rest   3.8       Primary Th2 rest   10.2       Primary Tr1 rest   4.2       CD45RA CD4 lymphocyte act   43.2       CD45RO CD4 lymphocyte act   72.2       CD8 lymphocyte act   10.4       Secondary CD8 lymphocyte rest   18.2       Secondary CD8 lymphocyte act   14.0       CD4 lymphocyte none   11.6       2ry Th1/Th2/Tr1_anti-CD95 CH11   10.6       LAK cells rest   23.8       LAK cells IL-2   18.8       LAK cells IL-2 + IL-12   0.0       LAK cells IL-2 + IFN gamma   45.4       LAK cells IL-2 + IL-18   12.9       LAK cells PMA/ionomycin   34.6       NK Cells IL-2 rest   68.3       Two Way MLR 3 day   31.6       Two Way MLR 5 day   4.5       Two Way MLR 7 day   22.2       PBMC rest   2.2       PBMC PWM   23.5       PBMC PHA-L   19.6       Ramos (B cell) none   28.7       Ramos (B cell) ionomycin   67.8       B lymphocytes PWM   20.6       B lymphocytes CD40L and IL-4   65.1       EOL-1 dbcAMP   34.4       EOL-1 dbcAMP PMA/ionomycin   6.9       Dendritic cells none   13.9       Dendritic cells LPS   7.2       Dendritic cells anti-CD40   9.6       Monocytes rest   21.8       Monocytes LPS   9.3       Macrophages rest   6.5       Macrophages LPS   8.5       HUVEC none   33.4       HUVEC starved   27.9       HUVEC IL-1beta   36.6       HUVEC IFN gamma   34.2       HUVEC TNF alpha + IFN gamma   13.4       HUVEC TNF alpha + IL4   14.1       HUVEC IL-11   28.5       Lung Microvascular EC none   100.0       Lung Microvascular EC TNFalpha + IL-1beta   21.2       Microvascular Dermal EC none   10.3       Microsvasular Dermal EC TNFalpha + IL-1beta   20.9       Bronchial epithelium TNFalpha + IL1beta   18.4       Small airway epithelium none   23.2       Small airway epithelium TNFalpha + IL-1beta   61.6       Coronery artery SMC rest   40.3       Coronery artery SMC TNFalpha + IL-1beta   55.1       Astrocytes rest   12.7       Astrocytes TNFalpha + IL-1beta   5.6       KU-812 (Basophil) rest   53.2       KU-812 (Basophil) PMA/ionomycin   51.4       CCD1106 (Keratinocytes) none   12.3       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   29.7       Liver cirrhosis   9.2       NCI-H292 none   98.6       NCI-H292 IL-4   77.9       NCI-H292 IL-9   62.4       NCI-H292 IL-13   100.0       NCI-H292 IFN gamma   45.1       HPAEC none   19.2       HPAEC TNF alpha + IL-1 beta   44.4       Lung fibroblast none   39.0       Lung fibroblast TNF alpha + IL-1 beta   53.2       Lung fibroblast IL-4   4.4       Lung fibroblast IL-9   15.8       Lung fibroblast IL-13   21.6       Lung fibroblast IFN gamma   36.3       Dermal fibroblast CCD1070 rest   25.9       Dermal fibroblast CCD1070 TNF alpha   74.7       Dermal fibroblast CCD1070 IL-1 beta   36.9       Dermal fibroblast IFN gamma   72.2       Dermal fibroblast IL-4   42.6       Dermal Fibroblasts rest   53.2       Neutrophils TNFa + LPS   4.2       Neutrophils rest   10.9       Colon   10.3       Lung   5.9       Thymus   5.8       Kidney   70.2                    
     [0625]               TABLE BD                          Panel CNS_1.1                                 Rel. Exp. (%)               Ag6505, Run           Tissue Name   271956643                                         Cing Gyr Depression2   8.9           Cing Gyr Depression   2.4           Cing Gyr PSP2   7.9           Cing Gyr PSP   15.4           Cing Gyr Huntington&#39;s2   22.2           Cing Gyr Huntington&#39;s   54.3           Cing Gyr Parkinson&#39;s2   31.4           Cing Gyr Parkinson&#39;s   33.4           Cing Gyr Alzheimer&#39;s2   13.2           Cing Gyr Alzheimer&#39;s   14.6           Cing Gyr Control2   25.5           Cing Gyr Control   66.9           Temp Pole Depression2   3.9           Temp Pole PSP2   7.8           Temp Pole PSP   0.0           Temp Pole Huntington&#39;s   28.5           Temp Pole Parkinson&#39;s2   39.0           Temp Pole Parkinson&#39;s   18.8           Temp Pole Alzheimer&#39;s2   9.5           Temp Pole Alzheimer&#39;s   12.2           Temp Pole Control2   29.5           Temp Pole Control   16.4           Glob Palladus Depression   8.6           Glob Palladus PSP2   5.7           Glob Palladus PSP   4.8           Glob Palladus Parkinson&#39;s2   18.4           Glob Palladus Parkinson&#39;s   90.8           Glob Palladus Alzheimer&#39;s2   10.5           Glob Palladus Alzheimer&#39;s   10.4           Glob Palladus Control2   9.5           Glob Palladus Control   30.6           Sub Nigra Depression2   2.1           Sub Nigra Depression   6.3           Sub Nigra PSP2   11.1           Sub Nigra Huntington&#39;s2   61.1           Sub Nigra Huntington&#39;s   35.6           Sub Nigra Parkinson&#39;s2   33.9           Sub Nigra Alzheimer&#39;s2   12.9           Sub Nigra Control2   17.8           Sub Nigra Control   45.1           BA17 Depression2   28.5           BA17 Depression   5.1           BA17 PSP2   10.6           BA17 PSP   14.0           BA17 Huntington&#39;s2   17.2           BA17 Huntington&#39;s   22.4           BA17 Parkinson&#39;s2   47.0           BA17 Parkinson&#39;s   79.6           BA17 Alzheimer&#39;s2   11.1           BA17 Control2   23.8           BA17 Control   28.3           BA9 Depression2   4.9           BA9 Depression   10.4           BA9 PSP2   1.8           BA9 PSP   4.2           BA9 Huntington&#39;s2   21.2           BA9 Huntington&#39;s   32.8           BA9 Parkinson&#39;s2   16.4           BA9 Parkinson&#39;s   34.4           BA9 Alzheimer&#39;s2   28.5           BA9 Alzheimer&#39;s   7.7           BA9 Control2   54.7           BA9 Control   37.4           BA7 Depression   7.0           BA7 PSP2   17.6           BA7 PSP   8.7           BA7 Huntington&#39;s2   100.0           BA7 Huntington&#39;s   31.4           BA7 Parkinson&#39;s2   32.1           BA7 Parkinson&#39;s   28.9           BA7 Alzheimer&#39;s2   7.8           BA7 Control2   24.1           BA7 Control   37.1           BA4 Depression2   10.8           BA4 Depression   13.2           BA4 PSP2   3.8           BA4 PSP   8.2           BA4 Huntington&#39;s2   25.2           BA4 Huntington&#39;s   13.2           BA4 Parkinson&#39;s2   42.9           BA4 Parkinson&#39;s   41.5           BA4 Alzheimer&#39;s2   2.8           BA4 Control2   33.0           BA4 Control   20.9                        
     [0626] General_screening anel_v1.6 Summary: Ag6505 Highest expression of this gene is detected in a ovarian cancer OVCAR-8 cell line (CT=29.7). Moderate to low levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.  
     [0627] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adrenal gland, thyroid, pituitary gland, fetal skeletal muscle, heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.  
     [0628] In addition, this gene is expressed at moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer&#39;s disease, Parkinson&#39;s disease, epilepsy, multiple sclerosis, schizophrenia and depression.  
     [0629] Panel 4.1D Summary: Ag6505 Highest expression of the CG134632-01 gene is detected in lung microvascular endothelial cells and IL-9 treated NCI-H292 cells (CTs=33.6). In addition, low levels of expression of this gene is also seen in activated primary and secondary Th1 and Th2 cells, activated CD4 lymphocytes, IL2 treated NK cells, TNFalpha+IL-1beta treated small airway epithelium and HPAEC cells, coronery artery SMC, basophils, TNFalpha +IL-1beta treated lung fibroblasts, and dermnal fibroblasts. Therefore, therapeutic modulation of this gene product may be useful in the treatment of autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     [0630] Low levels of expression of this gene is also seen in kidney. Therefore, small molecule therapies designed with the protein encoded for by this gene could modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.  
     [0631] Panel CNS — 1.1 Summary: Ag6505 This panel confirms the expression of the CG134632-01 gene at low levels in the brains of an independent group of individuals. Therefore, therapeutic modulation of this gene may be useful in the treatment of neurological disorder.  
     [0632] C. CG154077-01: SUR2.  
     [0633] Expression of gene CG154077-01 was assessed using the primer-probe set Ag5693, described in Table CA. Results of the RTQ-PCR runs are shown in Tables CB, CC, CD and CE.  
               TABLE CA                          Probe Name Ag5693                                                 SEQ                   Start   ID       Primers   Sequences   Length   Positions   No                                         Forward   5′-ctgtcacagatgcctgttctct-3′   22   2348   139               Probe   TET-5′-cagccagatattgacttattaccatttgga-3′-TAMRA   30   2371   140               Reverse   5′-cctctctccaatttcagtttga-3′   22   2403   141                  
 
     [0634]               TABLE CB                          General_screening_panel_v1.5                                 Rel. Exp. (%)               Ag5693, Run           Tissue Name   246263980                                         Adipose   18.2           Melanoma* Hs688(A).T   31.2           Melanoma* Hs688(B).T   18.0           Melanoma* M14   0.0           Melanoma* LOXIMVI   0.1           Melanoma* SK-MEL-5   0.0           Squamous cell carcinoma SCC-4   0.0           Testis Pool   0.7           Prostate ca.* (bone met) PC-3   0.0           Prostate Pool   9.1           Placenta   0.1           Uterus Pool   51.4           Ovarian ca. OVCAR-3   0.0           Ovarian ca. SK-OV-3   0.0           Ovarian ca. OVCAR-4   0.0           Ovarian ca. OVCAR-5   0.0           Ovarian ca. IGROV-1   0.0           Ovarian ca. OVCAR-8   0.0           Ovary   13.4           Breast ca. MCF-7   0.1           Breast ca. MDA-MB-231   0.4           Breast ca. BT 549   0.0           Breast ca. T47D   0.0           Breast ca. MDA-N   0.0           Breast Pool   29.3           Trachea   5.9           Lung   6.5           Fetal Lung   54.7           Lung ca. NCI-N417   0.0           Lung ca. LX-1   1.6           Lung ca. NCI-H146   0.0           Lung ca. SHP-77   0.0           Lung ca. A549   0.3           Lung ca. NCI-H526   0.0           Lung ca. NCI-H23   0.0           Lung ca. NCI-H460   2.8           Lung ca. HOP-62   0.0           Lung ca. NCI-H522   0.0           Liver   9.5           Fetal Liver   3.7           Liver ca. HepG2   0.0           Kidney Pool   98.6           Fetal Kidney   35.6           Renal ca. 786-0   0.1           Renal ca. A498   0.0           Renal ca. ACHN   1.2           Renal ca. UO-31   0.0           Renal ca. TK-10   0.0           Bladder   13.0           Gastric ca. (liver met.) NCI-N87   0.0           Gastric ca. KATO III   0.0           Colon ca. SW-948   0.0           Colon ca. SW480   0.7           Colon ca.* (SW480 met) SW620   0.5           Colon ca. HT29   0.0           Colon ca. HCT-116   0.0           Colon ca. CaCo-2   39.5           Colon cancer tissue   7.5           Colon ca. SW1116   0.0           Colon ca. Colo-205   0.0           Colon ca. SW-48   0.0           Colon Pool   45.4           Small Intestine Pool   38.4           Stomach Pool   19.5           Bone Marrow Pool   18.2           Fetal Heart   61.1           Heart Pool   40.1           Lymph Node Pool   50.7           Fetal Skeletal Muscle   32.8           Skeletal Muscle Pool   100.0           Spleen Pool   12.9           Thymus Pool   14.9           CNS cancer (glio/astro) U87-MG   0.1           CNS cancer (glio/astro) U-118-MG   4.9           CNS cancer (neuro; met) SK-N-AS   3.3           CNS cancer (astro) SF-539   0.0           CNS cancer (astro) SNB-75   0.0           CNS cancer (glio) SNB-19   0.0           CNS cancer (glio) SF-295   0.1           Brain (Amygdala) Pool   2.3           Brain (cerebellum)   1.4           Brain (fetal)   4.2           Brain (Hippocampus) Pool   1.9           Cerebral Cortex Pool   6.3           Brain (Substantia nigra) Pool   3.6           Brain (Thalamus) Pool   1.9           Brain (whole)   0.3           Spinal Cord Pool   8.0           Adrenal Gland   6.3           Pituitary gland Pool   2.3           Salivary Gland   0.6           Thyroid (female)   2.2           Pancreatic ca. CAPAN2   0.0           Pancreas Pool   34.4                        
     [0635]               TABLE CC                          General_screening_panel_v1.6                                 Rel. Exp. (%)               Ag5693, Run           Tissue Name   277231841                                         Adipose   28.3           Melanoma* Hs688(A).T   36.3           Melanoma* Hs688(B).T   16.6           Melanoma* M14   0.0           Melanoma* LOXIMVI   0.0           Melanoma* SK-MEL-5   0.0           Squamous cell carcinoma SCC-4   0.0           Testis Pool   7.3           Prostate ca.* (bone met) PC-3   0.0           Prostate Pool   13.4           Placenta   0.4           Uterus Pool   14.8           Ovarian ca. OVCAR-3   0.0           Ovarian ca. SK-OV-3   0.0           Ovarian ca. OVCAR-4   0.0           Ovarian ca. OVCAR-5   0.0           Ovarian ca. IGROV-1   0.0           Ovarian ca. OVCAR-8   0.0           Ovary   11.2           Breast ca. MCF-7   0.2           Breast ca. MDA-MB-231   0.3           Breast ca. BT 549   0.0           Breast ca. T47D   0.0           Breast ca. MDA-N   0.0           Breast Pool   40.1           Trachea   5.6           Lung   6.8           Fetal Lung   50.7           Lung ca. NCI-N417   0.0           Lung ca. LX-1   0.8           Lung ca. NCI-H146   0.0           Lung ca. SHP-77   0.0           Lung ca. A549   0.3           Lung ca. NCI-H526   0.0           Lung ca. NCI-H23   0.0           Lung ca. NCI-H460   49.0           Lung ca. HOP-62   0.1           Lung ca. NCI-H522   0.0           Liver   9.3           Fetal Liver   4.0           Liver ca. HepG2   0.0           Kidney Pool   100.0           Fetal Kidney   41.5           Renal ca. 786-0   0.0           Renal ca. A498   0.0           Renal ca. ACHN   8.8           Renal ca. UO-31   0.1           Renal ca. TK-10   0.0           Bladder   14.1           Gastric ca. (liver met.) NCI-N87   0.0           Gastric ca. KATO III   0.0           Colon ca. SW-948   0.0           Colon ca. SW480   0.5           Colon ca.* (SW480 met) SW620   0.9           Colon ca. HT29   0.0           Colon ca. HCT-116   0.0           Colon ca. CaCo-2   47.6           Colon cancer tissue   7.1           Colon ca. SW1116   0.0           Colon ca. Colo-205   0.0           Colon ca. SW-48   0.0           Colon Pool   44.8           Small Intestine Pool   48.6           Stomach Pool   23.7           Bone Marrow Pool   22.4           Fetal Heart   84.1           Heart Pool   46.7           Lymph Node Pool   55.5           Fetal Skeletal Muscle   37.4           Skeletal Muscle Pool   15.5           Spleen Pool   11.5           Thymus Pool   15.1           CNS cancer (glio/astro) U87-MG   0.2           CNS cancer (glio/astro) U-118-MG   5.6           CNS cancer (neuro; met) SK-N-AS   2.9           CNS cancer (astro) SF-539   0.0           CNS cancer (astro) SNB-75   0.0           CNS cancer (glio) SNB-19   0.0           CNS cancer (glio) SF-295   0.0           Brain (Amygdala) Pool   3.5           Brain (cerebellum)   2.1           Brain (fetal)   6.8           Brain (Hippocampus) Pool   5.9           Cerebral Cortex Pool   8.2           Brain (Substantia nigra) Pool   4.3           Brain (Thalamus) Pool   8.7           Brain (whole)   7.1           Spinal Cord Pool   8.8           Adrenal Gland   7.0           Pituitary gland Pool   2.3           Salivary Gland   0.6           Thyroid (female)   3.4           Pancreatic ca. CAPAN2   0.0           Pancreas Pool   6.2                        
     [0636]               TABLE CD                          Panel 4.1D                         Rel. Exp. (%)           Ag5693, Run       Tissue Name   268722540                             Secondary Th1 act   1.6       Secondary Th2 act   0.0       Secondary Tr1 act   0.0       Secondary Th1 rest   0.0       Secondary Th2 rest   0.0       Secondary Tr1 rest   0.0       Primary Th1 act   0.0       Primary Th2 act   0.0       Primary Tr1 act   0.0       Primary Th1 rest   0.0       Primary Th2 rest   0.0       Primary Tr1 rest   0.0       CD45RA CD4 lymphocyte act   21.5       CD45RO CD4 lymphocyte act   0.0       CD8 lymphocyte act   0.0       Secondary CD8 lymphocyte rest   0.0       Secondary CD8 lymphocyte act   0.0       CD4 lymphocyte none   0.0       2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0       LAK cells rest   0.0       LAK cells IL-2   0.0       LAK cells IL-2 + IL-12   0.0       LAK cells IL-2 + IFN gamma   0.0       LAK cells IL-2 + IL-18   0.0       LAK cells PMA/ionomycin   0.0       NK Cells IL-2 rest   0.0       Two Way MLR 3 day   0.0       Two Way MLR 5 day   0.0       Two Way MLR 7 day   0.0       PBMC rest   0.0       PBMC PWM   0.0       PBMC PHA-L   0.0       Ramos (B cell) none   0.0       Ramos (B cell) ionomycin   0.0       B lymphocytes PWM   0.0       B lymphocytes CD40L and IL-4   0.0       EOL-1 dbcAMP   0.0       EOL-1 dbcAMP PMA/ionomycin   0.0       Dendritic cells none   0.0       Dendritic cells LPS   0.0       Dendritic cells anti-CD40   0.0       Monocytes rest   0.0       Monocytes LPS   0.0       Macrophages rest   0.0       Macrophages LPS   0.0       HUVEC none   0.0       HUVEC starved   0.0       HUVEC IL-1beta   0.0       HUVEC IFN gamma   0.0       HUVEC TNF alpha + IFN gamma   0.0       HUVEC TNF alpha + IL4   0.0       HUVEC IL-11   0.0       Lung Microvascular EC none   0.0       Lung Microvascular EC TNFalpha + IL-1beta   0.0       Microvascular Dermal EC none   0.0       Microsvasular Dermal EC TNFalpha + IL-1beta   0.0       Bronchial epithelium TNFalpha + IL1beta   3.4       Small airway epithelium none   1.5       Small airway epithelium TNFalpha + IL-1beta   0.0       Coronery artery SMC rest   8.6       Coronery artery SMC TNFalpha + IL-1beta   10.4       Astrocytes rest   0.0       Astrocytes TNFalpha + IL-1beta   0.0       KU-812 (Basophil) rest   0.0       KU-812 (Basophil) PMA/ionomycin   0.0       CCD1106 (Keratinocytes) none   0.0       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   0.0       Liver cirrhosis   100.0       NCI-H292 none   0.0       NCI-H292 IL-4   0.0       NCI-H292 IL-9   0.0       NCI-H292 IL-13   0.0       NCI-H292 IFN gamma   0.0       HPAEC none   0.0       HPAEC TNF alpha + IL-1 beta   0.0       Lung fibroblast none   73.2       Lung fibroblast TNF alpha + IL-1 beta   2.4       Lung fibroblast IL-4   23.0       Lung fibroblast IL-9   57.4       Lung fibroblast IL-13   21.9       Lung fibroblast IFN gamma   86.5       Dermal fibroblast CCD1070 rest   74.7       Dermal fibroblast CCD1070 TNF alpha   60.3       Dermal fibroblast CCD1070 IL-1 beta   29.1       Dermal fibroblast IFN gamma   0.0       Dermal fibroblast IL-4   5.1       Dermal Fibroblasts rest   8.0       Neutrophils TNFa + LPS   0.0       Neutrophils rest   0.0       Colon   27.9       Lung   94.6       Thymus   8.7       Kidney   69.7                    
     [0637]               TABLE CE                          Panel 5 Islet                         Rel. Exp. (%)           Ag5693, Run       Tissue Name   243564603                             97457_Patient-02go_adipose   26.2       97476_Patient-07sk_skeletal muscle   41.5       97477_Patient-07ut_uterus   21.0       97478_Patient-07pl_placenta   5.4       99167_Bayer Patient 1   8.7       97482_Patient-08ut_uterus   7.7       97483_Patient-08pl_placenta   1.5       97486_Patient-09sk_skeletal muscle   16.2       97487_Patient-09ut_uterus   35.4       97488_Patient-09pl_placenta   1.7       97492_Patient-10ut_uterus   24.5       97493_Patient-10pl_placenta   2.4       97495_Patient-11go_adipose   19.3       97496_Patient-11sk_skeletal muscle   37.4       97497_Patient-11ut_uterus   20.3       97498_Patient-11pl_placenta   1.1       97500_Patient-12go_adipose   44.1       97501_Patient-12sk_skeletal muscle   100.0       97502_Patient-12ut_uterus   23.7       97503_Patient-12pl_placenta   0.8       94721_Donor 2 U - A_Mesenchymal Stem Cells   0.7       94722_Donor 2 U - B_Mesenchymal Stem Cells   0.9       94723_Donor 2 U - C_Mesenchymal Stem Cells   0.9       94709_Donor 2 AM - A_adipose   5.9       94710_Donor 2 AM - B_adipose   1.6       94711_Donor 2 AM - C_adipose   1.3       94712_Donor 2 AD - A_adipose   1.6       94713_Donor 2 AD - B_adipose   2.7       94714_Donor 2 AD - C_adipose   3.9       94742_Donor 3 U - A_Mesenchymal Stem Cells   0.4       94743_Donor 3 U - B_Mesenchymal Stem Cells   0.6       94730_Donor 3 AM - A_adipose   2.2       94731_Donor 3 AM - B_adipose   0.8       94732_Donor 3 AM - C_adipose   1.4       94733_Donor 3 AD - A_adipose   3.1       94734_Donor 3 AD - B_adipose   0.0       94735_Donor 3 AD - C_adipose   0.0       77138_Liver_HepG2untreated   0.4       73556_Heart_Cardiac stromal cells (primary)   0.0       81735_Small Intestine   31.2       72409_Kidney_Proximal Convoluted Tubule   1.2       82685_Small intestine_Duodenum   7.7       90650_Adrenal_Adrenocortical adenoma   1.8       72410_Kidney_HRCE   1.1       72411_Kidney_HRE   0.6       73139_Uterus_Uterine smooth muscle cells   3.1                    
     [0638] General_screening_panel_v1.5 Summary: Ag5693 Highest expression of this gene is detected in skeletal muscle (CT=29.6). This gene is expressed at moderate to low levels in tissues with metabolic or endocrine function including pancreas, adipose, adrenal gland, thyroid, skeletal muscle, heart, liver and the gastrointestinal tract. This gene codes for sulfonylurea Receptor 2 (SUR2). SUR2 is a member of the superfamily of ATP-binding cassette (ABC) transporters. It functions as a drug-binding regulatory subunit of the muscle specific ATP-sensitive potassium channel. Recent data showed that disruption of SUR2 leads to increased insulin stimulated glucose uptake in skeletal muscle. At Curagen, using GeneCalling studies, SUR2 was found to be up-regulated in fast twitch versus slow twitch muscle in mice on a high fat diet and in diabetic mice. It is known that glucose uptake is reduced in fast twitch muscle as compared to slow twitch muscle. Inhibition of SUR2 would favor slow twitch muscle phenotype, thus increasing glucose uptake and improving insulin sensitivity. Therefore, an antagonist of SUR2 may be an effective therapeutic against insulin resistance and diabetes.  
     [0639] In addition low expression of this gene is also seen in fetal brain, cerebral cortex, substantia nigra and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Parkinson&#39;s disease, epilepsy, multiple sclerosis, and seizures.  
     [0640] Low expression of this gene is also seen in some of the cancer cell lines derived from melanoma, colon, and brain cancers. Therefore, therapeutic modulatio of this gene or its protein product through the use of small molecule drug may be useful in the treatment of melanoma, colon and brain cancers.  
     [0641] See Chutkow W A, Samuel V, Hansen P A, Pu J, Valdivia C R, Makielski J C, Burant C F. Disruption of Sur2-containing K(ATP) channels enhances insulin-stimulated glucose uptake in skeletal muscle. Proc. Natl. Acad. Sci. USA 2001. 98,11760-4. PMID: 11562480; Chutkow W A, Simon M C, Le Beau M M, Burant C F. Cloning, tissue expression, and chromosomal localization of SUR2, the putative drug-binding subunit of cardiac, skeletal muscle, and vascular KATP channels. Diabetes 1996. 45,1439-45. PMID: 8826984; Halseth A E, Bracy D P, Wasserman D H. Functional limitations to glucose uptake in muscles comprised of different fiber types. Am. J. Physiol. Endocrinol. Metab. 2001. 280, E994-9. PMID: 11350781; Shindo T, Yamada M, Isomoto S, Horio Y, Kurachi Y. SUR2 subtype (A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandil. Br. J. Pharmacol. 1998. 124, 985-91. PMID: 9692785; Reimann F, Ashcroft F M, Gribble F M. Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes 2001. 50, 2253-9. PMID: 11574406; and Moreau C, Jacquet H, Prost A L, D&#39;hahan N, Vivaudou M. The molecular basis of the specificity of action of K(ATP) channel openers. EMBO J. 2000.19, 6644-51. PMID: 11118199.  
     [0642] General_screening_panel_v1.6 Summary: Ag5693 Highest expression of this gene is detected in kidney pool (CT=28.3). Expression of this gene in this panel is consistent with that seen in panel 1.5, please see panel 1.5 for further discussion of this gene.  
     [0643] Panel 4.1D Summary: Ag5693 Highest expression of this gene is detected in liver cirrhosis (CT=33.6). Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of liver cirrhosis.  
     [0644] Low expression of this gene is also seen in resting and activated lung and dermal fibroblast, kidney and lung. Therefore, therapeutic modulation of this gene or its protein product through the use of small molecule drug may be useful in the treatment of autoimmune and inflammatory disorders including psoriasis, lupus erythematosus, chronic obstructive pulmonary disease, asthma, allergy and emphysema.  
     [0645] Panel 5 Islet Summary: Ag5693 Highest expression of this gene is detected in skeletal muscle of a diabetic patient on insulin (CT=31). This gene is expressed at low levels in adipose and skeletal muscle of non-diabetic, and diabetic patient. The expression level of SUR2 is significantly elevated in diabetic adipose/skeletal muscle (patient 12) compared to non-diabetic individuals. These data further support that up-regulation of SUR2 has pathogenic consequences, and inhibition of SUR2 may be beneficial for the treatment of diabetes.  
     [0646] D. CG155759-02: Olfactory Receptor.  
     [0647] Expression of gene CG155759-02 was assessed using the primer-probe set Ag2298, described in Table DA. Please note that CG155759-02 represents a full length physical clone.  
               TABLE DA                          Probe Name Ag2298                                                 SEQ                   Start   ID       Primers   Sequences   Length   Positions   No                                         Forward   5′-ttcttgggagtttagcctttgt-3′   22   188   142               Probe   TET-5′-tgcttggatatcttccacagtaactccca-3′-TAMRA   29   213   143               Reverse   5′-ggccaagaaattaaccaacatt-3′   22   243   144                  
 
     [0648] CNS_neurodegeneration_v1.0 Summary: Ag2298 Expression of this gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0649] Panel 1.3D Summary: Ag2298 Expression of this gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0650] Panel 2.2 Summary: Ag2298 Expression of this gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0651] Panel 4.1D Summary: Ag2298 Expression of this gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0652] Panel 5 Islet Summary: Ag2298 Expression of this gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0653] E. CG155882-01: Olfactory Receptor.  
     [0654] Expression of gene CG155882-01 was assessed using the primer-probe set Ag2192, described in Table EA. Results of the RTQ-PCR runs are shown in Tables EB, EC, ED and EE.  
               TABLE EA                          Probe Name Ag2192                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-tgtattcatgggactcaccaa-3′   21   45   145               Probe   TET-5′-tcacgggagattcagcttctactttt-3′-TAMRA   26   67   146               Reverse   5′-gctcgcaaagtagaacaacaaa-3′   22   102   147                  
 
     [0655]               TABLE EB                          Panel 1.3D                                 Rel. Exp. (%)               Ag2192, Run           Tissue Name   165725843                                         Liver adenocarcinoma   0.0           Pancreas   0.0           Pancreatic ca. CAPAN 2   0.0           Adrenal gland   0.0           Thyroid   0.0           Salivary gland   0.0           Pituitary gland   0.0           Brain (fetal)   6.2           Brain (whole)   0.0           Brain (amygdala)   0.0           Brain (cerebellum)   0.0           Brain (hippocampus)   0.0           Brain (substantia nigra)   0.0           Brain (thalamus)   0.0           Cerebral Cortex   0.0           Spinal cord   0.0           glio/astro U87-MG   15.0           glio/astro U-118-MG   27.9           astrocytoma SW1783   14.1           neuro*; met SK-N-AS   0.0           astrocytoma SF-539   0.0           astrocytoma SNB-75   0.0           glioma SNB-19   0.0           glioma U251   96.6           glioma SF-295   10.4           Heart (fetal)   0.0           Heart   0.0           Skeletal muscle (fetal)   6.7           Skeletal muscle   0.0           Bone marrow   7.2           Thymus   9.3           Spleen   0.0           Lymph node   0.0           Colorectal   1.8           Stomach   0.0           Small intestine   0.0           Colon ca. SW480   0.0           Colon ca.* SW620(SW480 met)   0.0           Colon ca. HT29   0.0           Colon ca. HCT-116   3.3           Colon ca. CaCo-2   0.0           Colon ca. tissue(ODO3866)   0.0           Colon ca. HCC-2998   0.0           Gastric ca.* (liver met) NCI-N87   0.0           Bladder   0.0           Trachea   0.0           Kidney   0.0           Kidney (fetal)   6.5           Renal ca. 786-0   21.5           Renal ca. A498   27.9           Renal ca. RXF 393   32.8           Renal ca. ACHN   100.0           Renal ca. UO-31   7.9           Renal ca. TK-10   20.2           Liver   0.0           Liver (fetal)   0.0           Liver ca. (hepatoblast) HepG2   0.0           Lung   0.0           Lung (fetal)   3.0           Lung ca. (small cell) LX-1   1.1           Lung ca. (small cell) NCI-H69   0.0           Lung ca. (s. cell var.) SHP-77   0.0           Lung ca. (large cell)NCI-H460   0.0           Lung ca. (non-sm. cell) A549   0.0           Lung ca. (non-s. cell) NCI-H23   0.0           Lung ca. (non-s. cell) HOP-62   8.7           Lung ca. (non-s. cl) NCI-H522   2.9           Lung ca. (squam.) SW 900   14.8           Lung ca. (squam.) NCI-H596   0.0           Mammary gland   0.0           Breast ca.* (pl. ef) MCF-7   0.0           Breast ca.* (pl. ef) MDA-MB-231   0.0           Breast ca.* (pl. ef) T47D   0.0           Breast ca. BT-549   0.0           Breast ca. MDA-N   0.0           Ovary   5.8           Ovarian ca. OVCAR-3   0.0           Ovarian ca. OVCAR-4   0.0           Ovarian ca. OVCAR-5   0.0           Ovarian ca. OVCAR-8   0.0           Ovarian ca. IGROV-1   0.0           Ovarian ca.* (ascites) SK-OV-3   3.6           Uterus   0.0           Placenta   0.0           Prostate   3.2           Prostate ca.* (bone met)PC-3   0.0           Testis   0.0           Melanoma Hs688(A).T   0.0           Melanoma* (met) Hs688(B).T   0.0           Melanoma UACC-62   37.9           Melanoma M14   45.1           Melanoma LOX IMVI   3.7           Melanoma* (met) SK-MEL-5   0.0           Adipose   7.2                        
     [0656]               TABLE EC                          Panel 2D                         Rel. Exp. (%)           Ag2192, Run       Tissue Name   164024748                             Normal Colon   0.0       CC Well to Mod Diff (ODO3866)   12.9       CC Margin (ODO3866)   12.3       CC Gr.2 rectosigmoid (ODO3868)   0.0       CC Margin (ODO3868)   0.0       CC Mod Diff (ODO3920)   0.0       CC Margin (ODO3920)   0.0       CC Gr.2 ascend colon (ODO3921)   2.8       CC Margin (ODO3921)   2.1       CC from Partial Hepatectomy (ODO4309) Mets   0.0       Liver Margin (ODO4309)   0.0       Colon mets to lung (OD04451-01)   0.0       Lung Margin (OD04451-02)   0.0       Normal Prostate 6546-1   0.0       Prostate Cancer (OD04410)   0.0       Prostate Margin (OD04410)   0.0       Prostate Cancer (OD04720-01)   0.0       Prostate Margin (OD04720-02)   5.0       Normal Lung 061010   0.0       Lung Met to Muscle (ODO4286)   26.4       Muscle Margin (ODO4286)   0.0       Lung Malignant Cancer (OD03126)   0.0       Lung Margin (OD03126)   0.0       Lung Cancer (OD04404)   0.0       Lung Margin (OD04404)   0.0       Lung Cancer (OD04565)   0.0       Lung Margin (OD04565)   2.9       Lung Cancer (OD04237-01)   0.0       Lung Margin (OD04237-02)   0.0       Ocular Mel Met to Liver (ODO4310)   4.9       Liver Margin (ODO4310)   0.0       Melanoma Mets to Lung (OD04321)   2.5       Lung Margin (OD04321)   0.0       Normal Kidney   25.0       Kidney Ca, Nuclear grade 2 (OD04338)   100.0       Kidney Margin (OD04338)   4.6       Kidney Ca Nuclear grade 1/2 (OD04339)   48.0       Kidney Margin (OD04339)   18.9       Kidney Ca, Clear cell type (OD04340)   26.8       Kidney Margin (OD04340)   12.0       Kidney Ca, Nuclear grade 3 (OD04348)   7.0       Kidney Margin (OD04348)   2.5       Kidney Cancer (OD04622-01)   2.6       Kidney Margin (OD04622-03)   5.6       Kidney Cancer (OD04450-01)   89.5       Kidney Margin (OD04450-03)   7.2       Kidney Cancer 8120607   2.0       Kidney Margin 8120608   0.0       Kidney Cancer 8120613   0.0       Kidney Margin 8120614   7.2       Kidney Cancer 9010320   3.9       Kidney Margin 9010321   20.6       Normal Uterus   0.0       Uterus Cancer 064011   0.0       Normal Thyroid   0.0       Thyroid Cancer 064010   0.0       Thyroid Cancer A302152   1.7       Thyroid Margin A302153   2.5       Normal Breast   0.0       Breast Cancer (OD04566)   0.0       Breast Cancer (OD04590-01)   0.0       Breast Cancer Mets (OD04590-03)   0.0       Breast Cancer Metastasis (OD04655-05)   0.0       Breast Cancer 064006   0.0       Breast Cancer 1024   0.0       Breast Cancer 9100266   0.0       Breast Margin 9100265   0.0       Breast Cancer A209073   2.8       Breast Margin A209073   0.0       Normal Liver   0.0       Liver Cancer 064003   0.0       Liver Cancer 1025   2.0       Liver Cancer 1026   0.0       Liver Cancer 6004-T   5.4       Liver Tissue 6004-N   3.2       Liver Cancer 6005-T   0.0       Liver Tissue 6005-N   0.0       Normal Bladder   0.0       Bladder Cancer 1023   0.0       Bladder Cancer A302173   9.2       Bladder Cancer (OD04718-01)   0.0       Bladder Normal Adjacent (OD04718-03)   0.0       Normal Ovary   0.0       Ovarian Cancer 064008   0.0       Ovarian Cancer (OD04768-07)   0.0       Ovary Margin (OD04768-08)   0.0       Normal Stomach   0.0       Gastric Cancer 9060358   1.1       Stomach Margin 9060359   0.0       Gastric Cancer 9060395   2.1       Stomach Margin 9060394   2.1       Gastric Cancer 9060397   0.0       Stomach Margin 9060396   0.0       Gastric Cancer 064005   0.0                    
     [0657]               TABLE ED                          Panel 3D                         Rel. Exp. (%)           Ag2192, Run       Tissue Name   164795770                             Daoy- Medulloblastoma   0.0       TE671- Medulloblastoma   0.0       D283 Med- Medulloblastoma   0.0       PFSK-1- Primitive Neuroectodermal   0.0       XF-498- CNS   64.6       SNB-78- Glioma   1.8       SF-268- Glioblastoma   0.0       T98G- Glioblastoma   0.0       SK-N-SH- Neuroblastoma (metastasis)   0.0       SF-295- Glioblastoma   4.0       Cerebellum   0.0       Cerebellum   0.0       NCI-H292- Mucoepidermoid lung carcinoma   0.0       DMS-114- Small cell lung cancer   0.0       DMS-79- Small cell lung cancer   0.0       NCI-H146- Small cell lung cancer   0.0       NCI-H526- Small cell lung cancer   0.0       NCI-N417- Small cell lung cancer   0.0       NCI-H82- Small cell lung cancer   0.0       NCI-H157- Squamous cell lung cancer (metastasis)   0.0       NCI-H1155- Large cell lung cancer   0.0       NCI-H1299- Large cell lung cancer   1.1       NCI-H727- Lung carcinoid   0.0       NCI-UMC-11- Lung carcinoid   0.0       LX-1- Small cell lung cancer   0.0       Colo-205- Colon cancer   0.0       KM12- Colon cancer   0.0       KM20L2- Colon cancer   0.0       NCI-H716- Colon cancer   0.0       SW-48- Colon adenocarcinoma   0.0       SW1116- Colon adenocarcinoma   0.0       LS 174T- Colon adenocarcinoma   0.0       SW-948- Colon adenocarcinoma   0.0       SW-480- Colon adenocarcinoma   0.0       NCI-SNU-5- Gastric carcinoma   0.0       KATO III- Gastric carcinoma   0.0       NCI-SNU-16- Gastric carcinoma   7.5       NCI-SNU-1- Gastric carcinoma   0.0       RF-1- Gastric adenocarcinoma   0.0       RF-48- Gastric adenocarcinoma   0.0       MKN-45- Gastric carcinoma   0.0       NCI-N87- Gastric carcinoma   0.0       OVCAR-5- Ovarian carcinoma   0.0       RL95-2- Uterine carcinoma   0.0       HelaS3- Cervical adenocarcinoma   0.0       Ca Ski- Cervical epidermoid   1.2       carcinoma (metastasis)       ES-2- Ovarian clear cell carcinoma   6.1       Ramos- Stimulated with PMA/ionomycin 6 h   0.0       Ramos- Stimulated with PMA/ionomycin 14 h   0.0       MEG-01- Chronic myelogenous   0.0       leukemia (megokaryoblast)       Raji- Burkitt&#39;s lymphoma   4.4       Daudi- Burkitt&#39;s lymphoma   0.0       U266- B-cell plasmacytoma   0.0       CA46- Burkitt&#39;s lymphoma   0.0       RL- non-Hodgkin&#39;s B-cell lymphoma   0.0       JM1- pre-B-cell lymphoma   0.0       Jurkat- T cell leukemia   0.0       TF-1- Erythroleukemia   0.0       HUT 78- T-cell lymphoma   0.0       U937- Histiocytic lymphoma   0.0       KU-812- Myelogenous leukemia   0.0       769-P- Clear cell renal carcinoma   44.1       Caki-2- Clear cell renal carcinoma   100.0       SW 839- Clear cell renal carcinoma   22.1       Rhabdoid kidney tumor   0.0       Hs766T- Pancreatic carcinoma (LN metastasis)   0.0       CAPAN-1- Pancreatic adenocarcinoma   0.0       (liver metastasis)       SU86.86- Pancreatic carcinoma (liver metastasis)   0.0       BxPC-3- Pancreatic adenocarcinoma   0.0       HPAC- Pancreatic adenocarcinoma   0.0       MIA PaCa-2- Pancreatic carcinoma   0.0       CFPAC-1- Pancreatic ductal adenocarcinoma   0.0       PANC-1- Pancreatic epithelioid ductal carcinoma   0.0       T24- Bladder carcinma (transitional cell)   2.0       5637- Bladder carcinoma   0.0       HT-1197- Bladder carcinoma   0.0       UM-UC-3- Bladder carcinma (transitional cell)   0.0       A204- Rhabdomyosarcoma   0.0       HT-1080- Fibrosarcoma   29.1       MG-63- Osteosarcoma   0.0       SK-LMS-1- Leiomyosarcoma (vulva)   23.7       SJRH30- Rhabdomyosarcoma (met to bone marrow)   2.2       A431- Epidermoid carcinoma   0.0       WM266-4- Melanoma   22.5       DU 145- Prostate carcinoma (brain metastasis)   0.0       MDA-MB-468- Breast adenocarcinoma   0.0       SCC-4- Squamous cell carcinoma of tongue   0.0       SCC-9- Squamous cell carcinoma of tongue   0.0       SCC-15- Squamous cell carcinoma of tongue   0.0       CAL 27- Squamous cell carcinoma of tongue   0.0                    
     [0658]               TABLE EE                          Panel 4D                         Rel. Exp. (%)           Ag2192, Run       Tissue Name   163588121                             Secondary Th1 act   0.0       Secondary Th2 act   0.0       Secondary Tr1 act   12.3       Secondary Th1 rest   0.0       Secondary Th2 rest   0.0       Secondary Tr1 rest   0.0       Primary Th1 act   0.0       Primary Th2 act   0.0       Primary Tr1 act   0.0       Primary Th1 rest   0.0       Primary Th2 rest   0.0       Primary Tr1 rest   0.0       CD45RA CD4 lymphocyte act   0.0       CD45RO CD4 lymphocyte act   0.0       CD8 lymphocyte act   0.0       Secondary CD8 lymphocyte rest   0.0       Secondary CD8 lymphocyte act   0.0       CD4 lymphocyte none   0.0       2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0       LAK cells rest   0.0       LAK cells IL-2   0.0       LAK cells IL-2 + IL-12   0.0       LAK cells IL-2 + IFN gamma   0.0       LAK cells IL-2 + IL-18   0.0       LAK cells PMA/ionomycin   0.0       NK Cells IL-2 rest   0.0       Two Way MLR 3 day   0.0       Two Way MLR 5 day   0.0       Two Way MLR 7 day   0.0       PBMC rest   0.0       PBMC PWM   0.0       PBMC PHA-L   20.0       Ramos (B cell) none   0.0       Ramos (B cell) ionomycin   0.0       B lymphocytes PWM   20.9       B lymphocytes CD40L and IL-4   0.0       EOL-1 dbcAMP   0.0       EOL-1 dbcAMP PMA/ionomycin   0.0       Dendritic cells none   0.0       Dendritic cells LPS   0.0       Dendritic cells anti-CD40   0.0       Monocytes rest   0.0       Monocytes LPS   0.0       Macrophages rest   0.0       Macrophages LPS   0.0       HUVEC none   0.0       HUVEC starved   0.0       HUVEC IL-1beta   0.0       HUVEC IFN gamma   0.0       HUVEC TNF alpha + IFN gamma   0.0       HUVEC TNF alpha + IL4   0.0       HUVEC IL-11   0.0       Lung Microvascular EC none   0.0       Lung Microvascular EC TNFalpha + IL-1beta   24.3       Microvascular Dermal EC none   0.0       Microsvasular Dermal EC TNFalpha + IL-1beta   0.0       Bronchial epithelium TNFalpha + IL1beta   0.0       Small airway epithelium none   0.0       Small airway epithelium TNFalpha + IL-1beta   0.0       Coronery artery SMC rest   0.0       Coronery artery SMC TNFalpha + IL-1beta   0.0       Astrocytes rest   0.0       Astrocytes TNFalpha + IL-1beta   0.0       KU-812 (Basophil) rest   0.0       KU-812 (Basophil) PMA/ionomycin   0.0       CCD1106 (Keratinocytes) none   0.0       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   0.0       Liver cirrhosis   38.7       Lupus kidney   16.7       NCI-H292 none   0.0       NCI-H292 IL-4   0.0       NCI-H292 IL-9   0.0       NCI-H292 IL-13   0.0       NCI-H292 IFN gamma   0.0       HPAEC none   0.0       HPAEC TNF alpha + IL-1 beta   0.0       Lung fibroblast none   67.8       Lung fibroblast TNF alpha + IL-1 beta   0.0       Lung fibroblast IL-4   76.3       Lung fibroblast IL-9   65.1       Lung fibroblast IL-13   66.0       Lung fibroblast IFN gamma   0.0       Dermal fibroblast CCD1070 rest   0.0       Dermal fibroblast CCD1070 TNF alpha   22.2       Dermal fibroblast CCD1070 IL-1 beta   19.9       Dermal fibroblast IFN gamma   0.0       Dermal fibroblast IL-4   0.0       IBD Colitis 2   18.2       IBD Crohn&#39;s   0.0       Colon   40.6       Lung   0.0       Thymus   100.0       Kidney   0.0                    
     [0659] AI_comprehensive panel_v1.0 Summary: Ag2192 Expression of this gene is low/undetectable (CTs&gt;35) across all of the samples on this panel.  
     [0660] Panel 1.3D Summary: Ag2192 The expression of the CG155882-01 gene is highest in a sample derived from a renal cancer cell line (ACHN)(CT=33.3). In addition, there is expression in another renal cancer cell line, two melanoma cell lines and a glioma cell line. Thus the expression of this gene could be used to distinguish these samples from others in the panel. Moreover, targeting with a human monoclonal antibody of CG155882-01 that results in an inhibition of the signaling of this receptor will have therapeutic effect on these tumors, preferably on renal cell carcinoma and will result in reduced cell growth and proliferation  
     [0661] Panel 2D Summary: Ag2192 The expression of the CG155882-01 gene appears to be highest in a sample derived from a kidney cancer(CT=33.3). In addition, there appears to be substantial expression in several other kidney cancer samples. This result is in corcodance with the result seen in Panel 1.3D. Of note is the difference in expression between kidney cancer samples and their respective normal adjacent tissues. Thus, the expression of this gene could be used to distinguish kidney cancer samples from the rest of the samples in the panel. In addition, this data indicate that this GPCR has a role in Renal cell carcinoma progression, likely in cell growth and proliferation as it has been previous shown for other member of this family. Thus, therapeutic modulation of this gene, through the use of small molecule drugs, antibodies or protein therapeutics might be of benefit in the treatment of kidney cancer, preferably renal cell carcinoma.  
     [0662] Panel 3D Summary: Ag2192 The expression of the CG155882-01 gene appears to be highest in samples derived from kidney cancer cell lines (CT-32.6). This association with kidney cancer is also seen in Panels 1.3D and 2D. In addition, there is substantial expression seen in one brain cancer cell line, one fibrosarcoma cell line, one melanoma cell line and one leiomyosarcoma cell line. Thus, the expression of this gene could be used to distingish these samples from other samples in the panel. Moreover, therapeutic modulation of this gene, through the use of small molecule drugs, antibodies or protein therapeutics might be of benefit in the treatment of kidney cancer, melanoma, fiborsarcoma, brain cancer, or leiomyosarcoma.  
     [0663] Panel 4D Summary: Ag 2192 The expression of the CG155882-01 gene is higher in untreated fibroblasts than in fibroblasts treated by the potent inflammatory cytokines TNF-a and IFN-g cytokines but not by IL-4 cytokine. IL-4 has been associated with anti-inflammatory properties. TNF-a and IFNg have been shown to lead to the activation of proteolytic degradation of extracellular matrix in fibroblasts, a phenomenon associated with emphysema. IFN g has also been shown to lead to direct granulomatous inflammation of the lung. Therefore, therapeutic modulation of this gene product, through the use of small molecule drugs, or antibodies might be beneficial for the treatment of these diseases.  
     [0664] F. CG167853-01: CYTOPLASMIC ACETYL-COA HYDROLASE.  
     [0665] Expression of gene CG167853-01 was assessed using the primer-probe set Ag6104, described in Table FA. Results of the RTQ-PCR runs are shown in Tables FB and FC.  
               TABLE FA                          Probe Name Ag6104                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-acagtacatcagaagtgaaatcatatgt-3′   28   1509   148               Probe   TET-5′-ccatgctattgacagcaattcatgca-3′-TAMRA   26   1551   149               Reverse   5′-gctagcagacatatggttaaagtaagatac-3′   30   1579   150                  
 
     [0666]               TABLE FB                          General_screening_panel_v1.5                                 Rel. Exp. (%)               Ag6104, Run           Tissue Name   248491002                                         Adipose   0.0           Melanoma* Hs688(A).T   0.0           Melanoma* Hs688(B).T   0.0           Melanoma* M14   0.0           Melanoma* LOXIMVI   0.0           Melanoma* SK-MEL-5   48.6           Squamous cell carcinoma SCC-4   0.0           Testis Pool   1.5           Prostate ca.* (bone met) PC-3   1.4           Prostate Pool   0.0           Placenta   0.0           Uterus Pool   0.0           Ovarian ca. OVCAR-3   0.0           Ovarian ca. SK-OV-3   0.0           Ovarian ca. OVCAR-4   0.0           Ovarian ca. OVCAR-5   0.0           Ovarian ca. IGROV-1   0.5           Ovarian ca. OVCAR-8   0.0           Ovary   0.0           Breast ca. MCF-7   0.4           Breast ca. MDA-MB-231   0.4           Breast ca. BT 549   0.0           Breast ca. T47D   0.0           Breast ca. MDA-N   0.0           Breast Pool   0.3           Trachea   0.0           Lung   0.0           Fetal Lung   0.8           Lung ca. NCI-N417   0.0           Lung ca. LX-1   0.0           Lung ca. NCI-H146   0.0           Lung ca. SHP-77   0.0           Lung ca. A549   0.0           Lung ca. NCI-H526   0.0           Lung ca. NCI-H23   0.6           Lung ca. NCI-H460   0.0           Lung ca. HOP-62   0.5           Lung ca. NCI-H522   0.7           Liver   5.6           Fetal Liver   100.0           Liver ca. HepG2   0.0           Kidney Pool   0.3           Fetal Kidney   2.1           Renal ca. 786-0   0.0           Renal ca. A498   0.0           Renal ca. ACHN   0.0           Renal ca. UO-31   0.3           Renal ca. TK-10   0.0           Bladder   0.3           Gastric ca. (liver met.) NCI-N87   0.0           Gastric ca. KATO III   0.0           Colon ca. SW-948   0.0           Colon ca. SW480   0.0           Colon ca.* (SW480 met) SW620   0.0           Colon ca. HT29   0.0           Colon ca. HCT-116   0.0           Colon ca. CaCo-2   7.9           Colon cancer tissue   0.0           Colon ca. SW1116   0.0           Colon ca. Colo-205   0.0           Colon ca. SW-48   0.0           Colon Pool   0.0           Small Intestine Pool   0.3           Stomach Pool   0.0           Bone Marrow Pool   0.1           Fetal Heart   0.0           Heart Pool   0.0           Lymph Node Pool   0.0           Fetal Skeletal Muscle   0.0           Skeletal Muscle Pool   0.0           Spleen Pool   0.3           Thymus Pool   0.7           CNS cancer (glio/astro) U87-MG   0.0           CNS cancer (glio/astro) U-118-MG   0.6           CNS cancer (neuro; met) SK-N-AS   0.6           CNS cancer (astro) SF-539   0.0           CNS cancer (astro) SNB-75   0.1           CNS cancer (glio) SNB-19   0.6           CNS cancer (glio) SF-295   3.6           Brain (Amygdala) Pool   0.1           Brain (cerebellum)   0.3           Brain (fetal)   2.8           Brain (Hippocampus) Pool   0.8           Cerebral Cortex Pool   0.5           Brain (Substantia nigra) Pool   0.0           Brain (Thalamus) Pool   0.4           Brain (whole)   0.5           Spinal Cord Pool   10.5           Adrenal Gland   0.0           Pituitary gland Pool   0.0           Salivary Gland   0.0           Thyroid (female)   0.0           Pancreatic ca. CAPAN2   0.0           Pancreas Pool   0.0                        
     [0667]               TABLE FC                          Panel 4.1D                         Rel. Exp. (%)           Ag6104, Run       Tissue Name   248523701                             Secondary Th1 act   0.0       Secondary Th2 act   7.9       Secondary Tr1 act   0.0       Secondary Th1 rest   0.0       Secondary Th2 rest   0.0       Secondary Tr1 rest   0.0       Primary Th1 act   0.0       Primary Th2 act   0.0       Primary Tr1 act   0.0       Primary Th1 rest   0.0       Primary Th2 rest   0.0       Primary Tr1 rest   0.0       CD45RA CD4 lymphocyte act   0.0       CD45RO CD4 lymphocyte act   0.0       CD8 lymphocyte act   0.0       Secondary CD8 lymphocyte rest   0.0       Secondary CD8 lymphocyte act   0.0       CD4 lymphocyte none   2.9       2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0       LAK cells rest   0.0       LAK cells IL-2   0.0       LAK cells IL-2 + IL-12   0.0       LAK cells IL-2 + IFN gamma   0.0       LAK cells IL-2 + IL-18   0.0       LAK cells PMA/ionomycin   0.0       NK Cells IL-2 rest   0.0       Two Way MLR 3 day   0.0       Two Way MLR 5 day   0.0       Two Way MLR 7 day   0.0       PBMC rest   0.0       PBMC PWM   0.0       PBMC PHA-L   0.0       Ramos (B cell) none   0.0       Ramos (B cell) ionomycin   0.0       B lymphocytes PWM   0.0       B lymphocytes CD40L and IL-4   0.0       EOL-1 dbcAMP   0.0       EOL-1 dbcAMP PMA/ionomycin   0.0       Dendritic cells none   0.0       Dendritic cells LPS   0.0       Dendritic cells anti-CD40   0.0       Monocytes rest   0.0       Monocytes LPS   0.0       Macrophages rest   0.0       Macrophages LPS   0.0       HUVEC none   0.0       HUVEC starved   0.0       HUVEC IL-1beta   0.0       HUVEC IFN gamma   0.0       HUVEC TNF alpha + IFN gamma   0.0       HUVEC TNF alpha + IL4   0.0       HUVEC IL-11   0.0       Lung Microvascular EC none   0.0       Lung Microvascular EC TNFalpha + IL-1beta   0.0       Microvascular Dermal EC none   0.0       Microsvasular Dermal EC TNFalpha + IL-1beta   0.0       Bronchial epithelium TNFalpha + IL1beta   0.0       Small airway epithelium none   0.0       Small airway epithelium TNFalpha + IL-1beta   0.0       Coronery artery SMC rest   0.0       Coronery artery SMC TNFalpha + IL-1beta   0.0       Astrocytes rest   0.0       Astrocytes TNFalpha + IL-1beta   0.0       KU-812 (Basophil) rest   0.0       KU-812 (Basophil) PMA/ionomycin   3.5       CCD1106 (Keratinocytes) none   0.0       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   0.0       Liver cirrhosis   23.5       NCI-H292 none   0.0       NCI-H292 IL-4   0.0       NCI-H292 IL-9   2.7       NCI-H292 IL-13   0.0       NCI-H292 IFN gamma   0.0       HPAEC none   0.0       HPAEC TNF alpha + IL-1 beta   0.0       Lung fibroblast none   33.2       Lung fibroblast TNF alpha + IL-1 beta   0.0       Lung fibroblast IL-4   16.3       Lung fibroblast IL-9   20.3       Lung fibroblast IL-13   0.0       Lung fibroblast IFN gamma   7.0       Dermal fibroblast CCD1070 rest   0.0       Dermal fibroblast CCD1070 TNF alpha   0.0       Dermal fibroblast CCD1070 IL-1 beta   0.0       Dermal fibroblast IFN gamma   0.0       Dermal fibroblast IL-4   4.8       Dermal Fibroblasts rest   0.0       Neutrophils TNFa + LPS   0.0       Neutrophils rest   0.0       Colon   3.0       Lung   0.0       Thymus   5.3       Kidney   100.0                    
     [0668] CNS_neurodegeneration_v1.0 Summary: Ag6104 Expression of this gene is low/undetectable (CTs&gt;35) across all of the samples on this panel.  
     [0669] General_screening_panel_v1.5 Summary: Ag6104 Highest expression of this gene is seen mainly in fetal liver (CT=29.9). Low expression of this gene is also seen in adult liver. Interestingly, this gene is expressed at much higher levels in fetal (CT=29.9) when compared to adult liver (CT=34.1). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.  
     [0670] Moderate to low expression of this gene is also seen in a few cell lines derived from melanoma, colon and brain cancer. Therefore, therapeutic modulation of this gene may be useful in the treatment of melanoma, colon and brain cancers.  
     [0671] Panel 4.1D Summary: Ag6104 Low expression of this gene is seen mainly in kidney (CT=33.4). Therefore, antibody or small molecule therapies designed with the protein encoded for by this gene could modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.  
     [0672] Panel 5 Islet Summary: Ag6104 Expression of this gene is low/undetectable (CTs&gt;35) across all of the samples on this panel due to a probable probe or chemistry failure.  
     [0673] G. CG167873-01: P2X Purinoceptor 5.  
     [0674] Expression of gene CG167873-01 was assessed using the primer-probe set Ag6266, described in Table GA. Results of the RTQ-PCR runs are shown in Tables GB and GC.  
               TABLE GA                          Probe Name Ag6266                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-gaagacttcaccattttcataaagaac-3′   27   571   151               Probe   TET-5′-ttcaacttctccaaccgtctggacaa-3′-TAMRA   26   616   152               Reverse   5′-cggagqagacagagtttgaaa-3′   21   647   153                  
 
     [0675]               TABLE GB                          General_screening_panel_v1.5                                 Rel. Exp. (%)               Ag6266, Run           Tissue Name   258845656                                         Adipose   6.5           Melanoma* Hs688(A).T   6.7           Melanoma* Hs688(B).T   0.0           Melanoma* M14   4.9           Melanoma* LOXIMVI   0.0           Melanoma* SK-MEL-5   0.0           Squamous cell carcinoma SCC-4   0.0           Testis Pool   0.0           Prostate ca.* (bone met) PC-3   0.0           Prostate Pool   0.0           Placenta   0.0           Uterus Pool   0.0           Ovarian ca. OVCAR-3   0.0           Ovarian ca. SK-OV-3   0.0           Ovarian ca. OVCAR-4   7.7           Ovarian ca. OVCAR-5   15.5           Ovarian ca. IGROV-1   0.0           Ovarian ca. OVCAR-8   0.0           Ovary   0.0           Breast ca. MCF-7   2.0           Breast ca. MDA-MB-231   0.0           Breast ca. BT 549   20.2           Breast ca. T47D   0.0           Breast ca. MDA-N   5.6           Breast Pool   0.0           Trachea   1.6           Lung   0.0           Fetal Lung   0.0           Lung ca. NCI-N417   0.0           Lung ca. LX-1   2.8           Lung ca. NCI-H146   15.5           Lung ca. SHP-77   0.0           Lung ca. A549   6.9           Lung ca. NCI-H526   0.0           Lung ca. NCI-H23   19.1           Lung ca. NCI-H460   5.0           Lung ca. HOP-62   7.3           Lung ca. NCI-H522   14.7           Liver   0.0           Fetal Liver   0.0           Liver ca. HepG2   1.8           Kidney Pool   0.0           Fetal Kidney   0.0           Renal ca. 786-0   0.0           Renal ca. A498   3.8           Renal ca. ACHN   24.5           Renal ca. UO-31   100.0           Renal ca. TK-10   3.3           Bladder   3.2           Gastric ca. (liver met.) NCI-N87   0.0           Gastric ca. KATO III   0.0           Colon ca. SW-948   0.0           Colon ca. SW480   34.4           Colon ca.* (SW480 met) SW620   43.5           Colon ca. HT29   0.0           Colon ca. HCT-116   0.0           Colon ca. CaCo-2   0.0           Colon cancer tissue   0.0           Colon ca. SW1116   0.0           Colon ca. Colo-205   0.0           Colon ca. SW-48   0.0           Colon Pool   0.0           Small Intestine Pool   2.6           Stomach Pool   0.0           Bone Marrow Pool   0.0           Fetal Heart   0.0           Heart Pool   0.0           Lymph Node Pool   0.0           Fetal Skeletal Muscle   7.2           Skeletal Muscle Pool   17.4           Spleen Pool   1.9           Thymus Pool   2.7           CNS cancer (glio/astro) U87-MG   0.0           CNS cancer (glio/astro) U-118-MG   5.8           CNS cancer (neuro; met) SK-N-AS   0.0           CNS cancer (astro) SF-539   0.0           CNS cancer (astro) SNB-75   6.1           CNS cancer (glio) SNB-19   0.0           CNS cancer (glio) SF-295   2.9           Brain (Amygdala) Pool   0.0           Brain (cerebellum)   12.5           Brain (fetal)   4.2           Brain (Hippocampus) Pool   0.0           Cerebral Cortex Pool   0.0           Brain (Substantia nigra) Pool   0.0           Brain (Thalamus) Pool   0.0           Brain (whole)   26.4           Spinal Cord Pool   74.7           Adrenal Gland   2.8           Pituitary gland Pool   0.0           Salivary Gland   0.0           Thyroid (female)   0.0           Pancreatic ca. CAPAN2   0.0           Pancreas Pool   0.0                        
     [0676]               TABLE GC                          Panel 4.1D                         Rel. Exp. (%)           Ag6266, Run       Tissue Name   258923092                             Secondary Th1 act   100.0       Secondary Th2 act   31.6       Secondary Tr1 act   1.6       Secondary Th1 rest   3.2       Secondary Th2 rest   2.1       Secondary Tr1 rest   0.0       Primary Th1 act   6.9       Primary Th2 act   12.2       Primary Tr1 act   19.8       Primary Th1 rest   0.0       Primary Th2 rest   0.0       Primary Tr1 rest   1.9       CD45RA CD4 lymphocyte act   21.3       CD45RO CD4 lymphocyte act   34.6       CD8 lymphocyte act   0.0       Secondary CD8 lymphocyte rest   8.7       Secondary CD8 lymphocyte act   0.0       CD4 lymphocyte none   0.0       2ry Th1/Th2/Tr1_anti-CD95 CH11   8.2       LAK cells rest   0.0       LAK cells IL-2   0.0       LAK cells IL-2 + IL-12   5.2       LAK cells IL-2 + IFN gamma   0.0       LAK cells IL-2 + IL-18   2.3       LAK cells PMA/ionomycin   0.0       NK Cells IL-2 rest   6.3       Two Way MLR 3 day   5.3       Two Way MLR 5 day   1.9       Two Way MLR 7 day   13.5       PBMC rest   0.0       PBMC PWM   2.7       PBMC PHA-L   3.0       Ramos (B cell) none   7.1       Ramos (B cell) ionomycin   6.0       B lymphocytes PWM   0.6       B lymphocytes CD40L and IL-4   14.7       EOL-1 dbcAMP   2.2       EOL-1 dbcAMP PMA/ionomycin   0.0       Dendritic cells none   0.0       Dendritic cells LPS   0.0       Dendritic cells anti-CD40   0.0       Monocytes rest   0.7       Monocytes LPS   0.0       Macrophages rest   0.0       Macrophages LPS   0.0       HUVEC none   0.0       HUVEC starved   0.0       HUVEC IL-1beta   0.0       HUVEC IFN gamma   0.0       HUVEC TNF alpha + IFN gamma   0.0       HUVEC TNF alpha + IL4   0.0       HUVEC IL-11   0.0       Lung Microvascular EC none   0.0       Lung Microvascular EC TNFalpha + IL-1beta   0.0       Microvascular Dermal EC none   0.0       Microsvasular Dermal EC TNFalpha + IL-1beta   0.0       Bronchial epithelium TNFalpha + IL1beta   0.0       Small airway epithelium none   0.0       Small airway epithelium TNFalpha + IL-1beta   0.0       Coronery artery SMC rest   0.0       Coronery artery SMC TNFalpha + IL-1beta   0.0       Astrocytes rest   0.0       Astrocytes TNFalpha + IL-1beta   0.0       KU-812 (Basophil) rest   5.1       KU-812 (Basophil) PMA/ionomycin   9.0       CCD1106 (Keratinocytes) none   1.9       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   0.0       Liver cirrhosis   0.0       NCI-H292 none   6.0       NCI-H292 IL-4   2.7       NCI-H292 IL-9   0.6       NCI-H292 IL-13   1.5       NCI-H292 IFN gamma   0.0       HPAEC none   0.0       HPAEC TNF alpha + IL-1 beta   0.0       Lung fibroblast none   0.0       Lung fibroblast TNF alpha + IL-1 beta   0.0       Lung fibroblast IL-4   0.0       Lung fibroblast IL-9   0.0       Lung fibroblast IL-13   0.0       Lung fibroblast IFN gamma   0.0       Dermal fibroblast CCD1070 rest   2.7       Dermal fibroblast CCD1070 TNF alpha   0.0       Dermal fibroblast CCD1070 IL-1 beta   0.0       Dermal fibroblast IFN gamma   0.0       Dermal fibroblast IL-4   0.0       Dermal Fibroblasts rest   0.0       Neutrophils TNFa + LPS   0.0       Neutrophils rest   0.0       Colon   0.0       Lung   0.0       Thymus   0.0       Kidney   0.0                    
     [0677] CNS_neurodegeneration_v1.0 Summary: Ag6266 Expression of this gene is low/undetectable (CTs&gt;35) across all of the samples on this panel.  
     [0678] General_screening_panel_v1.5 Summary: Ag6266 Low expression of this gene is mainly detected in a renal cancer UO-31 cell line (CT=33.9). Therefore, expression of this gene may be used as a diagnostic marker for renal cancer. Furthermore, therapeutic modulation of this gene or its protein product through the use of small molecule drug may be used to treat renal cancer.  
     [0679] Low expression of this gene is also seen in spinal cord sample. Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of neurological disorders that affect spinal cord.  
     [0680] Panel 4.1D Summary: Ag6266 Highest expression of this gene is detected in activated secondary Th1 cells (CT=31.9). In addition, low expression of this gene is also in activated primary Tr1, Th2 and activated secondary Th2, naive T cells, and memory T cells. The expression pattern of this gene in T cells suggests that it may therefore be important in T cell polarization. Thus, therapeutic regulation of the transcript or the protein encoded by the transcript could be important in immune modulation and in the treatment of T cell-mediated diseases such as asthma, arthritis, psoriasis, IBD including Crohns disease and ulcerativ colitis, and lupus.  
     [0681] H. CG167873-02: P2X Purinoceptor 5.  
     [0682] Expression of gene CG167873-02 was assessed using the primer-probe set Ag6267, described in Table HA. Results of the RTQ-PCR runs are shown in Tables HB and HC.  
               TABLE HA                          Probe Name Ag6267                                             Start   SEQ       Primers   Seqnences   Length   Position   ID No                                         Forward   5′-atgggtgctggtgctttc-3′   18   938   154               Probe   TET-5′-tctgcgacctggtactcatctacctca-3′-TAMRA   27   957   155               Reverse   5′-gtacttcttgtcacggtaaaactctct-3′   27   992   156                  
 
     [0683]               TABLE HB                          General_screening_panel_v1.5                                 Rel. Exp. (%)               Ag6267, Run           Tissue Name   258845657                                         Adipose   0.0           Melanoma* Hs688(A).T   0.0           Melanoma* Hs688(B).T   0.0           Melanoma* M14   0.0           Melanoma* LOXIMVI   0.0           Melanoma* SK-MEL-5   0.0           Squamous cell carcinoma SCC-4   0.0           Testis Pool   0.0           Prostate ca.* (bone met) PC-3   0.0           Prostate Pool   0.0           Placenta   0.0           Uterus Pool   0.0           Ovarian ca. OVCAR-3   0.0           Ovarian ca. SK-OV-3   0.0           Ovarian ca. OVCAR-4   0.0           Ovarian ca. OVCAR-5   0.0           Ovarian ca. IGROV-1   0.0           Ovarian ca. OVCAR-8   0.0           Ovary   0.0           Breast ca. MCF-7   0.0           Breast ca. MDA-MB-231   0.0           Breast ca. BT 549   0.0           Breast ca. T47D   0.0           Breast ca. MDA-N   0.0           Breast Pool   0.0           Trachea   0.0           Lung   0.0           Fetal Lung   0.0           Lung ca. NCI-N417   0.0           Lung ca. LX-1   0.1           Lung ca. NCI-H146   0.0           Lung ca. SHP-77   0.0           Lung ca. A549   0.0           Lung ca. NCI-H526   0.0           Lung ca. NCI-H23   100.0           Lung ca. NCI-H460   0.2           Lung ca. HOP-62   0.0           Lung ca. NCI-H522   0.0           Liver   0.0           Fetal Liver   3.3           Liver ca. HepG2   0.0           Kidney Pool   0.0           Fetal Kidney   0.0           Renal ca. 786-0   0.0           Renal ca. A498   0.0           Renal ca. ACHN   0.0           Renal ca. UO-31   0.0           Renal ca. TK-10   0.0           Bladder   0.0           Gastric ca. (liver met.) NCI-N87   0.0           Gastric ca. KATO III   0.0           Colon ca. SW-948   0.0           Colon ca. SW480   0.2           Colon ca.* (SW480 met) SW620   0.1           Colon ca. HT29   0.0           Colon ca. HCT-116   0.0           Colon ca. CaCo-2   0.0           Colon cancer tissue   0.0           Colon ca. SW1116   0.0           Colon ca. Colo-205   0.0           Colon ca. SW-48   0.0           Colon Pool   0.0           Small Intestine Pool   0.0           Stomach Pool   0.0           Bone Marrow Pool   0.0           Fetal Heart   0.0           Heart Pool   0.0           Lymph Node Pool   0.0           Fetal Skeletal Muscle   0.0           Skeletal Muscle Pool   24.8           Spleen Pool   12.9           Thymus Pool   0.0           CNS cancer (glio/astro) U87-MG   0.0           CNS cancer (glio/astro) U-118-MG   0.1           CNS cancer (neuro; met) SK-N-AS   0.0           CNS cancer (astro) SF-539   0.0           CNS cancer (astro) SNB-75   0.0           CNS cancer (glio) SNB-19   0.0           CNS cancer (glio) SF-295   0.0           Brain (Amygdala) Pool   0.0           Brain (cerebellum)   0.0           Brain (fetal)   0.0           Brain (Hippocampus) Pool   0.0           Cerebral Cortex Pool   0.0           Brain (Substantia nigra) Pool   0.3           Brain (Thalamus) Pool   0.0           Brain (whole)   0.0           Spinal Cord Pool   0.0           Adrenal Gland   0.0           Pituitary gland Pool   0.0           Salivary Gland   0.0           Thyroid (female)   0.0           Pancreatic ca. CAPAN2   0.0           Pancreas Pool   0.0                        
     [0684]               TABLE HC                          Panel 4.1D                         Rel. Exp. (%)           Ag6267, Run       Tissue Name   258921627                             Secondary Th1 act   3.2       Secondary Th2 act   0.0       Secondary Tr1 act   1.7       Secondary Th1 rest   0.0       Secondary Th2 rest   0.0       Secondary Tr1 rest   0.0       Primary Th1 act   0.0       Primary Th2 act   0.0       Primary Tr1 act   0.0       Primary Th1 rest   0.0       Primary Th2 rest   0.0       Primary Tr1 rest   0.0       CD45RA CD4 lymphocyte act   0.0       CD45RO CD4 lymphocyte act   0.0       CD8 lymphocyte act   0.0       Secondary CD8 lymphocyte rest   0.0       Secondary CD8 lymphocyte act   0.0       CD4 lymphocyte none   0.0       2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0       LAK cells rest   0.0       LAK cells IL-2   0.0       LAK cells IL-2 + IL-12   0.0       LAK cells IL-2 + IFN gamma   0.0       LAK cells IL-2 + IL-18   0.0       LAK cells PMA/ionomycin   0.0       NK Cells IL-2 rest   0.0       Two Way MLR 3 day   0.6       Two Way MLR 5 day   0.0       Two Way MLR 7 day   0.0       PBMC rest   0.0       PBMC PWM   0.0       PBMC PHA-L   0.0       Ramos (B cell) none   0.0       Ramos (B cell) ionomycin   0.0       B lymphocytes PWM   0.0       B lymphocytes CD40L and IL-4   1.3       EOL-1 dbcAMP   0.0       EOL-1 dbcAMP PMA/ionomycin   0.0       Dendritic cells none   0.0       Dendritic cells LPS   0.0       Dendritic cells anti-CD40   0.0       Monocytes rest   0.0       Monocytes LPS   0.0       Macrophages rest   0.0       Macrophages LPS   0.0       HUVEC none   0.0       HUVEC starved   0.0       HUVEC IL-1beta   0.0       HUVEC IFN gamma   0.0       HUVEC TNF alpha + IFN gamma   0.0       HUVEC TNF alpha + IL4   0.0       HUVEC IL-11   0.0       Lung Microvascular EC none   0.0       Lung Microvascular EC TNFalpha + IL-1beta   0.0       Microvascular Dermal EC none   0.0       Microsvasular Dermal EC TNFalpha + IL-1beta   0.0       Bronchial epithelium TNFalpha + IL1beta   0.0       Small airway epithelium none   0.0       Small airway epithelium TNFalpha + IL-1beta   0.0       Coronery artery SMC rest   0.0       Coronery artery SMC TNFalpha + IL-1beta   0.0       Astrocytes rest   0.0       Astrocytes TNFalpha + IL-1beta   0.0       KU-812 (Basophil) rest   0.0       KU-812 (Basophil) PMA/ionomycin   1.1       CCD1106 (Keratinocytes) none   0.0       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   0.0       Liver cirrhosis   0.0       NCI-H292 none   46.0       NCI-H292 IL-4   59.9       NCI-H292 IL-9   49.0       NCI-H292 IL-13   100.0       NCI-H292 IFN gamma   62.4       HPAEC none   0.0       HPAEC TNF alpha + IL-1 beta   0.0       Lung fibroblast none   0.0       Lung fibroblast TNF alpha + IL-1 beta   0.0       Lung fibroblast IL-4   0.0       Lung fibroblast IL-9   0.0       Lung fibroblast IL-13   0.0       Lung fibroblast IFN gamma   0.0       Dermal fibroblast CCD1070 rest   0.0       Dermal fibroblast CCD1070 TNF alpha   0.0       Dermal fibroblast CCD1070 IL-1 beta   0.0       Dermal fibroblast IFN gamma   0.0       Dermal fibroblast IL-4   0.0       Dermal Fibroblasts rest   0.0       Neutrophils TNFa + LPS   0.0       Neutrophils rest   0.0       Colon   0.0       Lung   0.0       Thymus   0.0       Kidney   0.0                    
     [0685] CNS_neurodegeneration_v1.0 Summary: Ag6267 Expression of this gene is low/undetectable (CTs&gt;35) across all of the samples on this panel.  
     [0686] General_screening panel_v1.5 Summary: Ag6267 Highest expression of this gene is mainly seen in a lung cancer NCI-H23 cell line (CT=29.2). Therefore, expression of this gene may be used as diagnostic marker to detect the presence of lung cancer and also, therapeutic modulation of this gene may be useful in the treatment of lung cancer.  
     [0687] In addition, moderate expression of this gene is also seen in skeletal muscle and thymus. Therefore, therapeutic modulation of this gene through the use of small molecule drug may be useful in the treatment of muscle related diseases and T cell mediated autoimmune or inflammatory diseases, including asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis.  
     [0688] Panel 4.1D Summary: Ag6267 Highest expression of this gene is seen in IL-13 activated NCI-H292 cells (CT=31.3). Moderate expression of this gene is restricted to resting and activated NCI-H292 cells. The expression of this gene in this mucoepidermoid cell line that is often used as a model for airway epithelium (NCI-H292 cells) suggests that this gene may be important in the proliferation or activation of airway epithelium. Therefore, therapeutics designed with the protein encoded by this gene may reduce or eliminate symptoms caused by inflammation in lung epithelia in chronic obstructive pulmonary disease, asthma, allergy, and emphysema.  
     [0689] I. CG108945-02: Cation-transporting ATPase 1.  
     [0690] Expression of gene CG108945-02 was assessed using the primer-probe set Ag6263, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB and IC.  
               TABLE IA                          Probe Name Ag6263                                             Start   ID       Primers   Sequences   Length   Position   No                                     Forward   5′-tgaatggcgttaaggtcctg-3′20   2433   157               Probe   TET-5′-ttctgtagctcgcaccagctctgtctt-3′-TAMRA   29   2492   158               Reverse   5′-gtgagaccactgaggcttctg-3′   21   2610   159                  
 
     [0691]               TABLE LB                          CNS_neurodegeneration_v1.0                                 Rel.               Exp4%)               Ag6263,               Run           Tissue Name   258816990                                         AD 1 Hippo   3.7           AD 2 Hippo   37.4           AD 3 Hippo   0.7           AD 4 Hippo   14.5           AD 5 hippo   24.7           AD 6 Hippo   33.2           Control 2 Hippo   46.3           Control 4 Hippo   16.6           Control (Path) 3 Hippo   10.8           AD 1 Temporal Ctx   1.0           AD 2 Temporal Ctx   27.2           AD 3 Temporal Ctx   11.1           AD 4 Temporal Ctx   12.0           AD 5 Inf Temporal Ctx   21.8           AD 5 SupTemporal Ctx   14.0           AD 6 Inf Temporal Ctx   13.9           AD 6 Sup Temporal Ctx   11.7           Control 1 Temporal Ctx   4.1           Control 2 Temporal Ctx   99.3           Control 3 Temporal Ctx   13.3           Control 4 Temporal Ctx   4.9           Control (Path) 1 Temporal Ctx   56.3           Control (Path) 2 Temporal Ctx   32.8           Control (Path) 3 Temporal Ctx   2.2           Control (Path) 4 Temporal Ctx   22.4           AD 1 Occipital Ctx   2.2           AD 2 Occipital Ctx (Missing)   0.0           AD 3 Occipital Ctx   0.0           AD 4 Occipital Ctx   20.9           AD 5 Occipital Ctx   11.8           AD 6 Occipital Ctx   43.5           Control 1 Occipital Ctx   10.7           Control 2 Occipital Ctx   65.1           Control 3 Occipital Ctx   10.4           Control 4 Occipital Ctx   3.0           Control (Path) 1 Occipital Ctx   88.3           Control (Path) 2 Occipital Ctx   6.7           Control (Path) 3 Occipital Ctx   1.3           Control (Path) 4 Occipital Ctx   12.3           Control 1 Parietal Ctx   3.9           Control 2 Parietal Ctx   5.7           Control 3 Parietal Ctx   13.9           Control (Path) 1 Parietal Ctx   100.0           Control (Path) 2 Parietal Ctx   17.1           Control (Path) 3 Parietal Ctx   1.4           Control (Path) 4 Parietal Ctx   64.2                        
     [0692]               TABLE IC                          General_screening_panel_v1.5                                 Rel. Exp. (%)               Ag6263,               Run           Tissue Name   258875091                                         Adipose   1.9           Melanoma* Hs688(A).T   9.9           Melanoma* Hs688(B).T   16.2           Melanoma* M14   12.9           Melanoma* LOXIMVI   5.8           Melanoma* SK-MEL-5   13.8           Squamous cell carcinoma SCC-4   9.9           Testis Pool   6.2           Prostate ca.* (bone met) PC-3   0.4           Prostate Pool   1.7           Placenta   6.5           Uterus Pool   0.4           Ovarian ca. OVCAR-3   2.0           Ovarian ca. SK-OV-3   23.7           Ovarian ca. OVCAR-4   5.2           Ovarian ca. OVCAR-5   25.3           Ovarian ca. IGROV-1   42.6           Ovarian ca. OVCAR-8   92.0           Ovary   1.8           Breast ca. MCF-7   39.2           Breast ca. MDA-MB-231   30.4           Breast ca. BT 549   15.1           Breast ca. T47D   6.8           Breast ca. MDA-N   12.3           Breast Pool   1.5           Trachea   5.9           Lung   0.5           Fetal Lung   6.1           Lung ca. NCI-N417   4.3           Lung ca. LX-1   19.9           Lung ca. NCI-H146   8.7           Lung ca. SHP-77   32.3           Lung ca. A549   11.4           Lung ca. NCI-H526   10.2           Lung ca. NCI-H23   12.2           Lung ca. NCI-H460   13.2           Lung ca. HOP-62   10.4           Lung ca. NCI-H522   14.0           Liver   0.3           Fetal Liver   3.8           Liver ca. HepG2   16.7           Kidney Pool   6.1           Fetal Kidney   4.6           Renal ca. 786-0   9.6           Renal ca. A498   4.7           Renal ca. ACHN   5.8           Renal ca. UO-31   18.0           Renal ca. TK-10   17.8           Bladder   15.4           Gastric ca. (liver met.) NCI-N87   44.8           Gastric ca. KATO III   70.7           Colon ca. SW-948   10.4           Colon ca. SW480   50.3           Colon ca.* (SW480 met) SW620   28.3           Colon ca. HT29   17.4           Colon ca. HCT-116   33.9           Colon ca. CaCo-2   12.6           Colon cancer tissue   11.4           Colon ca. SW1116   11.0           Colon ca. Colo-205   1.7           Colon ca. SW-48   13.0           Colon Pool   1.5           Small Intestine Pool   2.3           Stomach Pool   0.6           Bone Marrow Pool   0.3           Fetal Heart   0.7           Heart Pool   2.0           Lymph Node Pool   4.5           Fetal Skeletal Muscle   2.4           Skeletal Muscle Pool   5.2           Spleen Pool   1.4           Thymus Pool   2.1           CNS cancer (glio/astro) U87-MG   11.3           CNS cancer (glio/astro) U-118-MG   12.5           CNS cancer (neuro; met) SK-N-AS   12.9           CNS cancer (astro) SF-539   19.5           CNS cancer (astro) SNB-75   31.6           CNS cancer (glio) SNB-19   25.9           CNS cancer (glio) SF-295   86.5           Brain (Amygdala) Pool   61.1           Brain (cerebellum)   89.5           Brain (fetal)   100.0           Brain (Hippocampus) Pool   88.3           Cerebral Cortex Pool   95.9           Brain (Substantia nigra) Pool   88.3           Brain (Thalamus) Pool   89.5           Brain (whole)   97.3           Spinal Cord Pool   27.2           Adrenal Gland   3.3           Pituitary gland Pool   2.6           Salivary Gland   6.9           Thyroid (female)   3.9           Pancreatic ca. CAPAN2   4.6           Pancreas Pool   6.3                        
     [0693] CNS_neurodegeneration_v1.0 Summary: Ag6263 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene is found to be slightly down-regulated in the temporal cortex of Alzheimer&#39;s disease patients. Therefore, up-regulation of this gene or its protein product, or treatment with specific agonists for this receptor may be of use in reversing the dementia/memory loss associated with this disease and neuronal death.  
     [0694] General_screening panel_v1.5 Summary: Ag6263 Highest expression of this gene is detected in fetal brain and all the adult brain region including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, and cerebral cortex (CTs=30). Moderate expression of this gene is also seen in 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.  
     [0695] Moderate to low levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.  
     [0696] Among tissues with metabolic or endocrine function, this gene is expressed at low levels in pancreas, thyroid, skeletal muscle, and fetal liver. 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.  
     [0697] Interestingly, this gene is expressed at much higher levels in fetal (CTs=34-34.8) when compared to adult lung and liver (CTs=38). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.  
     [0698] Panel 4.1D Summary: Ag6263 Expression of this gene is low/undetectable (CTs&gt;35) across all of the samples on this panel.  
     [0699] J. CG167893-01: P450.  
     [0700] Expression of gene CG167893-01 was assessed using the primer-probe set Ag6107, described in Table JA.  
               TABLE JA                          Probe Name Ag6107                                                 SEQ                   Start   ID       Primers   Sequences   Length   Position   No                                         Forward   5′-gaagttctctcattcaactcttcgt-3′   25   564   160               Probe   TET-5′-cgaggcctagaaatctgtctgaacagtcaagt-3′-TAMRA   32   799   161               Reverse   5′-ccaatgatataaaataagtactcttcatca-3′   30   1041   162                  
 
     [0701] CNS-neurodegeneration_v1.0 Summary: Ag6107 Expression of this gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0702] General_screening panel_v1.5 Summary: Ag6107 Expression of this gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0703] K CG169088-01: Plasma Membrane Calcium-transporting ATPase 3.  
     [0704] Expression of gene CG169088-01 was assessed using the primer-probe set Ag6111, described in Table KA.  
               TABLE KA                          Probe Name Ag6111                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-agcttcatgacgtaaccaatctt-3′   23   3479   163               Probe   TET-5′-ctacccctactcacatccgggtggt-3′-TAMRA   25   3503   164               Reverse   5′-gtttctccaggccttcatagag-3′   22   3547   165                  
 
     [0705] CNS_neurodegeneration_v1.0 Summary: Ag6111 Expression of this gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0706] General_screening panel_v1.5 Summary: Ag61 μl Expression of this gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0707] Panel 4.1D Summary: Ag6111 Expression of this gene is low/undetectable in all samples on this panel (CTs&gt;35).  
     [0708] L. CG169201-01: Potential Phospholipid-transporting ATPase IH.  
     [0709] Expression of gene CG169201-01 was assessed using the primer-probe sets Ag6123, Ag7799 and Ag7814, described in Tables LA, LB and LC. Results of the RTQ-PCR runs are shown in Tables LD, LE and LF.  
               TABLE LA                          Probe Name Ag6123                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-gacagaacatcaggaatatggattaat-3′   27   2677   166               Probe   TET-5′-catagatggctccacatttgtcactca-3′-TAMRA   26   2704   167               Reverse   5′-gtaattgtttgaactagagtcttgactagaat-3′   32   2736   168                  
 
     [0710]               TABLE LB                          Probe Name Ag7799                                                 SEQ                   Start   ID       Primers   Sequences   Length   Position   No                                         Forward   5′-cacacgcacagtgtttgttg-3′   20   508   169               Probe   TET-5′-tcatccagtttcggaaacagaagcttacat-3′-TAMRA   30   532   170               Reverse   5′-attccaaagtgtatacttagatgagactattc-3′   32   585   171                    
     [0711]               TABLE LC                          Probe Name Ag7814                                                 SEQ                   Start   ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tttgttgqcaatcatccagt-3′   20   521   172               Probe   TET-5′-tcacaaaatctttgtgcaatgtaagcttct-3′-TAMRA   30   550   173               Reverse   5′-aaattccaaagtgtatacttagatgagac-3′   29   590   174                    
     [0712]               TABLE LD                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)               Ag7799,               Run           Tissue Name   312372413                                         AD 1 Hippo   21.8           AD 2 Hippo   18.9           AD 3 Hippo   10.0           AD 4 Hippo   5.3           AD 5 hippo   9.2           AD 6 Hippo   100.0           Control 2 Hippo   29.3           Control 4 Hippo   25.2           Control (Path) 3 Hippo   17.0           AD 1 Temporal Ctx   49.3           AD 2 Temporal Ctx   22.5           AD 3 Temporal Ctx   10.2           AD 4 Temporal Ctx   18.9           AD 5 Inf Temporal Ctx   5.3           AD 5 Sup Temporal Ctx   5.4           AD 6 Inf Temporal Ctx   86.5           AD 6 Sup Temporal Ctx   84.1           Control 1 Temporal Ctx   8.6           Control 2 Temporal Ctx   34.9           Control 3 Temporal Ctx   19.3           Control 4 Temporal Ctx   14.4           Control (Path) 1 Temporal Ctx   47.3           Control (Path) 2 Temporal Ctx   31.4           Control (Path) 3 Temporal Ctx   13.8           Control (Path) 4 Temporal Ctx   42.6           AD 1 Occipital Ctx   23.8           AD 2 Occipital Ctx (Missing)   0.0           AD 3 Occipital Ctx   17.3           AD 4 Occipital Ctx   11.7           AD 5 Occipital Ctx   30.6           AD 6 Occipital Ctx   24.1           Control 1 Occipital Ctx   14.4           Control 2 Occipital Ctx   37.6           Control 3 Occipital Ctx   20.6           Control 4 Occipital Ctx   8.1           Control (Path) 1 Occipital Ctx   19.1           Control (Path) 2 Occipital Ctx   14.9           Control (Path) 3 Occipital Ctx   14.1           Control (Path) 4 Occipital Ctx   36.3           Control 1 Parietal Ctx   12.5           Control 2 Parietal Ctx   87.1           Control 3 Parietal Ctx   13.7           Control (Path) 1 Parietal Ctx   32.1           Control (Path) 2 Parietal Ctx   18.3           Control (Path) 3 Parietal Ctx   21.9           Control (Path) 4 Parietal Ctx   39.2                        
     [0713]               TABLE LE                          General_screening_panel_v1.5                                 Rel. Exp. (%)               Ag6123,               Run           Tissue Name   259048762                                         Adipose   11.7           Melanoma* Hs688(A).T   23.5           Melanoma* Hs688(B).T   39.0           Melanoma* M14   28.5           Melanoma* LOXIMVI   25.3           Melanoma* SK-MEL-5   33.9           Squamous cell carcinoma SCC-4   10.9           Testis Pool   8.7           Prostate ca.* (bone met) PC-3   42.3           Prostate Pool   11.5           Placenta   1.1           Uterus Pool   17.7           Ovarian ca. OVCAR-3   42.3           Ovarian ca. SK-OV-3   38.7           Ovarian ca. OVCAR-4   15.4           Ovarian ca. OVCAR-5   27.4           Ovarian ca. IGROV-1   14.6           Ovarian ca. OVCAR-8   8.4           Ovary   12.3           Breast ca. MCF-7   41.5           Breast ca. MDA-MB-231   27.2           Breast ca. BT 549   100.0           Breast ca. T47D   3.3           Breast ca. MDA-N   22.2           Breast Pool   24.5           Trachea   8.0           Lung   5.5           Fetal Lung   22.1           Lung ca. NCI-N417   20.2           Lung ca. LX-1   32.3           Lung ca. NCI-H146   2.9           Lung ca. SHP-77   36.3           Lung ca. A549   25.2           Lung ca. NCI-H526   9.0           Lung ca. NCI-H23   28.1           Lung ca. NCI-H460   37.9           Lung ca. HOP-62   20.0           Lung ca. NCI-H522   61.1           Liver   1.6           Fetal Liver   16.3           Liver ca. HepG2   9.8           Kidney Pool   21.8           Fetal Kidney   20.2           Renal ca. 786-0   35.4           Renal ca. A498   11.0           Renal ca. ACHN   14.4           Renal ca. UO-31   13.3           Renal ca. TK-10   20.7           Bladder   17.6           Gastric ca. (liver met.) NCI-N87   36.1           Gastric ca. KATO III   44.8           Colon ca. SW-948   1.1           Colon ca. SW480   94.0           Colon ca.* (SW480 met) SW620   54.3           Colon ca. HT29   1.7           Colon ca. HCT-116   21.9           Colon ca. CaCo-2   20.9           Colon cancer tissue   17.6           Colon ca. SW1116   5.2           Colon ca. Colo-205   0.3           Colon ca. SW-48   3.6           Colon Pool   21.8           Small Intestine Pool   16.3           Stomach Pool   12.6           Bone Marrow Pool   8.8           Fetal Heart   4.4           Heart Pool   5.2           Lymph Node Pool   25.2           Fetal Skeletal Muscle   3.6           Skeletal Muscle Pool   7.1           Spleen Pool   18.9           Thymus Pool   19.6           CNS cancer (glio/astro) U87-MG   31.6           CNS cancer (glio/astro) U-118-MG   34.6           CNS cancer (neuro; met) SK-N-AS   97.3           CNS cancer (astro) SF-539   10.2           CNS cancer (astro) SNB-75   55.5           CNS cancer (glio) SNB-19   17.1           CNS cancer (glio) SF-295   46.0           Brain (Amygdala) Pool   2.4           Brain (cerebellum)   8.0           Brain (fetal)   18.9           Brain (Hippocampus) Pool   5.0           Cerebral Cortex Pool   3.7           Brain (Substantia nigra) Pool   2.4           Brain (Thalamus) Pool   4.6           Brain (whole)   2.4           Spinal Cord Pool   4.6           Adrenal Gland   5.7           Pituitary gland Pool   0.8           Salivary Gland   2.0           Thyroid (female)   2.4           Pancreatic ca. CAPAN2   38.7           Pancreas Pool   20.2                        
     [0714]               TABLE LF                          Panel 5 Islet                         Rel. Exp. (%)           Ag6123,           Run       Tissue Name   253579196                             97457_Patient-02go_adipose   19.3       97476_Patient-07sk_skeletal muscle   6.5       97477_Patient-07ut_uterus   21.2       97478_Patient-07pl_placenta   10.4       99167_Bayer Patient 1   1.2       97482_Patient-08ut_uterus   13.3       97483_Patient-08pl_placenta   7.5       97486_Patient-09sk_skeletal muscle   4.0       97487_Patient-09ut_uterus   21.2       97488_Patient-09pl_placenta   7.4       97492_Patient-10ut_uterus   20.4       97493_Patient-10pl_placenta   15.5       97495_Patient-11go_adipose   16.6       97496_Patient-11sk_skeletal muscle   5.0       97497_Patient-11ut_uterus   29.1       97498_Patient-11pl_placenta   6.7       97500_Patient-12go_adipose   17.7       97501_Patient-12sk_skeletal muscle   8.3       97502_Patient-12ut_uterus   40.9       97503_Patient-12pl_placenta   10.0       94721_Donor 2 U - A_Mesenchymal Stem Cells   40.1       94722_Donor 2 U - B_Mesenchymal Stem Cells   29.5       94723_Donor 2 U - C_Mesenchymal Stem Cells   28.7       94709_Donor 2 AM - A_adipose   95.3       94710_Donor 2 AM - B_adipose   42.0       94711_Donor 2 AM - C_adipose   40.1       94712_Donor 2 AD - A_adipose   54.7       94713_Donor 2 AD - B_adipose   94.0       94714_Donor 2 AD - C_adipose   81.8       94742_Donor 3 U - A_Mesenchymal Stem Cells   26.4       94743_Donor 3 U - B_Mesenchymal Stem Cells   35.6       94730_Donor 3 AM - A_adipose   100.0       94731_Donor 3 AM - B_adipose   61.6       94732_Donor 3 AM - C_adipose   72.7       94733_Donor 3 AD - A_adipose   50.3       94734_Donor 3 AD - B_adipose   55.5       94735_Donor 3 AD - C_adipose   67.4       77138_Liver_HepG2untreated   47.0       73556_Heart_Cardiac stromal cells (primary)   20.9       81735_Small Intestine   19.3       72409_Kidney_Proximal Convoluted Tubule   37.6       82685_Small intestine_Duodenum   15.5       90650_Adrenal_Adrenocortical adenoma   9.5       72410_Kidney_HRCE   52.9       72411_Kidney_HRE   36.3       73139_Uterus_Uterine smooth muscle cells   33.7                    
     [0715] CNS_neurodegeneration_v1.0 Summary: Ag7799 This panel does not show differential expression of this gene in Alzheimer&#39;s disease. However, this profile confirms the expression of this gene at moderate levels in the brain. Please see Panel 1.5 for discussion of this gene in the central nervous system.  
     [0716] General_screening panel_v1.5 Summary: Ag6123 Highest expression of this gene is seen in a breast cancer cell line (CT=27.9). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.  
     [0717] 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.  
     [0718] In addition, this gene is expressed at much higher levels in fetal lung, liver and skeletal muscle 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 tissue  
     [0719] Interestingly, this gene is expressed at much higher levels in fetal liver tissue (CT=30.5) when compared to the level of expression in the adult counterpart (CT=33.8). This observation suggests that expression of this gene can be used to distinguish between the fetal and adult sources of this tissue. In addition, the relative overexpression of this gene in fetal liver suggests that the protein product may enhance the growth or development of this organ in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver related diseases.  
     [0720] 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.  
     [0721] Panel 5 Islet Summary: Ag6123 Highest expression of this gene is seen in adipose (CT=31.1). Moderate to low levels of expression are seen in other metabolic tissues, including placenta and skeletal muscle. Please see Panel 1.5 for discussion of this gene in metabolic disease.  
     [0722] M. CG50303-03: Olfactory Receptor.  
     [0723] Expression of gene CG50303-03 was assessed using the primer-probe sets Ag1501, Ag1585, Ag2377, Ag2607 and Ag2610, described in Tables MA, MB, MC, MD and ME. Results of the RTQ-PCR runs are shown in Tables MF, MG, MH, MI, MJ, MK and ML.  
               TABLE MA                          Probe Name Ag1501                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-catagctgacacccacctacat-3′   22   159   175               Probe   TET-5′-cacccatgtacttcttcctgggcaat-3′-TAMRA   26   182   176               Reverse   5′-ctgcagtcatggttaccaagat-3′   22   223   177                  
 
     [0724]               TABLE MB                          Probe Name Ag1585                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-catagctgacacccacctacat-3′   22   159   178               Probe   TET-5′-cacccatgtacttcttcctgggcaat-3′-TAMRA   26   182   179               Reverse   5′-ctgcagtcatggttaccaagat-3′   22   223   180                    
     [0725]               TABLE MC                          Probe Name Ag2377                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-atgggaaacaccatcatcatag-3′   22   159   181               Probe   TET-5′-tggtcatagctgacacccacctacat-3′-TAMRA   26   155   182               Reverse   5′-aattgcccaggaagaagtacat-3′   22   187   183                    
     [0726]               TABLE MD                          Probe Name Ag2607                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-catagctgacacccacctacat-3′   22   159   184               Probe   TET-5′-cacccatgtacttcttcctgggcaat-3′-TAMRA   26   182   185               Reverse   5′-actgcagtcatggttaccaaga-3′   22   224   186                    
     [0727]               TABLE ME                          Probe Name Ag2610                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-gtctcacctcacactggtcttc-3′   22   738   187               Probe   TET-5′-catctttctgtatgtcaggcctggca-3′-TAMRA   26   777   188               Reverse   5′-ctgacttgcacagagtgagctt-3′   22   803   189                    
     [0728]               TABLE MF                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)           Ag2377, Run   Ag2607, Run   Ag2610, Run       Tissue Name   208271229   208971580   208393679                                     AD 1 Hippo   9.2   4.5   14.9       AD 2 Hippo   10.7   15.1   45.7       AD 3 Hippo   8.8   8.5   18.7       AD 4 Hippo   7.2   9.0   4.8       AD 5 hippo   32.5   44.4   48.0       AD 6 Hippo   100.0   35.6   33.9       Control 2   24.0   33.4   22.5       Hippo       Control 4   5.6   7.4   13.9       Hippo       Control (Path)   4.0   6.2   0.0       3 Hippo       AD 1   36.6   60.3   27.4       Temporal Ctx       AD 2   18.3   39.5   46.3       Temporal Ctx       AD 3   10.1   10.3   18.9       Temporal Ctx       AD 4   30.4   52.5   31.9       Temporal Ctx       AD 5 Inf   35.1   85.3   52.5       Temporal Ctx       AD 5   10.7   36.6   28.7       SupTemporal       Ctx       AD 6 Inf   27.5   87.7   60.7       Temporal Ctx       AD 6 Sup   22.4   72.2   52.5       Temporal Ctx       Control 1   3.9   15.6   6.0       Temporal Ctx       Control 2   7.6   11.6   13.0       Temporal Ctx       Control 3   9.7   12.6   4.4       Temporal Ctx       Control 4   11.5   15.4   6.8       Temporal Ctx       Control (Path)   43.8   67.4   36.3       1 Temporal Ctx       Control (Path)   17.8   35.6   22.4       2 Temporal Ctx       Control (Path)   1.4   1.4   0.0       3 Temporal       Ctx       Control (Path)   18.2   35.1   36.9       4 Temporal       Ctx       AD 1   16.3   35.6   17.7       Occipital       Ctx       AD 2   0.0   0.0   0.0       Occipital       Ctx       (Missing)       AD 3   10.3   13.0   18.9       Occipital       Ctx       AD 4   16.4   57.4   20.0       Occipital       Ctx       AD 5   11.8   27.5   22.4       Occipital       Ctx       AD 6   3.6   18.0   13.6       Occipital       Ctx       Control 1   7.2   7.7   2.6       Occipital       Ctx       Control 2   0.1   55.5   25.3       Occipital       Ctx       Control 3   19.3   29.1   32.3       Occipital       Ctx       Control 4   10.0   20.9   8.2       Occipital       Ctx       Control   62.9   100.0   100.0       (Path) 1       Occipital       Ctx       Control   23.5   47.6   12.9       (Path) 2       Occipital       Ctx       Control   1.1   2.2   5.2       (Path) 3       Occipital       Ctx       Control   30.8   46.0   39.2       (Path) 4       Occipital       Ctx       Control 1   14.3   35.1   10.0       Parietal       Ctx       Control 2   17.4   61.1   30.6       Parietal       Ctx       Control 3   15.5   26.2   25.7       Parietal       Ctx       Control   27.2   60.3   64.6       (Path) 1       Parietal       Ctx       Control   57.0   54.7   43.8       (Path) 2       Parietal       Ctx       Control   2.0   0.0   7.3       (Path) 3       Parietal       Ctx       Control   48.3   65.5   82.9       (Path) 4       Parietal       Ctx                    
     [0729]               TABLE MG                          Panel 1.2                                 Rel. Exp. (%)               Ag1501,               Run           Tissue Name   140466099                                         Endothelial cells   6.8           Heart (Fetal)   0.3           Pancreas   0.6           Pancreatic ca. CAPAN 2   0.3           Adrenal Gland   16.4           Thyroid   0.0           Salivary gland   38.2           Pituitary gland   1.2           Brain (fetal)   20.6           Brain (whole)   13.3           Brain (amygdala)   17.2           Brain (cerebellum)   7.0           Brain (hippocampus)   67.4           Brain (thalamus)   92.0           Cerebral Cortex   85.3           Spinal cord   25.0           glio/astro U87-MG   17.0           glio/astro U-118-MG   5.5           astrocytoma SW1783   7.2           neuro*; met SK-N-AS   1.5           astrocytoma SF-539   2.4           astrocytoma SNB-75   14.2           glioma SNB-19   23.5           glioma U251   6.9           glioma SF-295   18.8           Heart   50.7           Skeletal Muscle   13.2           Bone marrow   7.5           Thymus   0.0           Spleen   4.6           Lymph node   2.9           Colorectal Tissue   9.3           Stomach   0.7           Small intestine   6.5           Colon ca. SW480   1.5           Colon ca.* SW620 (SW480 met)   16.2           Colon ca. HT29   14.7           Colon ca. HCT-116   7.6           Colon ca. CaCo-2   9.4           Colon ca. Tissue (ODO3866)   31.2           Colon ca. HCC-2998   10.3           Gastric ca.* (liver met) NCI-N87   21.3           Bladder   36.6           Trachea   0.0           Kidney   35.8           Kidney (fetal)   14.9           Renal ca. 786-0   14.3           Renal ca. A498   12.6           Renal ca. RXF 393   15.9           Renal ca. ACHN   11.8           Renal ca. UO-31   21.0           Renal ca. TK-10   28.3           Liver   7.6           Liver (fetal)   5.1           Liver ca. (hepatoblast) HepG2   9.9           Lung   0.0           Lung (fetal)   0.9           Lung ca. (small cell) LX-1   33.9           Lung ca. (small cell) NCI-H69   58.6           Lung ca. (s. cell var.) SHP-77   3.6           Lung ca. (large cell)NCI-H460   24.0           Lung ca. (non-sm. cell) A549   30.8           Lung ca. (non-s. cell) NCI-H23   81.8           Lung ca. (non-s. cell) HOP-62   24.3           Lung ca. (non-s. cl) NCI-H522   59.0           Lung ca. (squam.) SW 900   10.4           Lung ca. (squam.) NCI-H596   25.7           Mammary gland   15.3           Breast ca.* (pl. ef) MCF-7   2.1           Breast ca.* (pl. ef) MDA-MB-231   2.3           Breast ca.* (pl. ef) T47D   88.9           Breast ca. BT-549   6.1           Breast ca. MDA-N   74.7           Ovary   0.7           Ovarian ca. OVCAR-3   14.3           Ovarian ca. OVCAR-4   40.3           Ovarian ca. OVCAR-5   72.7           Ovarian ca. OVCAR-8   100.0           Ovarian ca. IGROV-1   56.3           Ovarian ca. (ascites) SK-OV-3   16.4           Uterus   9.5           Placenta   39.0           Prostate   8.8           Prostate ca.* (bone met) PC-3   39.0           Testis   14.0           Melanoma Hs688(A).T   1.3           Melanoma* (met) Hs688(B).T   10.6           Melanoma UACC-62   48.6           Melanoma M14   69.7           Melanoma LOX IMVI   0.0           Melanoma* (met) SK-MEL-5   9.7                        
     [0730]               TABLE MH                          Panel 1.3D                                     Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)           Ag1585,   Ag2377,   Ag2607,   Ag2610,           Run   Run   Run   Run       Tissue Name   165529870   165631765   166219825   166162989                                         Liver adenocarcinoma   5.1   5.6   0.0   0.0       Pancreas   0.0   0.0   0.0   0.0       Pancreatic ca. CAPAN 2   0.0   0.0   0.0   5.6       Adrenal gland   0.0   0.0   0.0   0.0       Thyroid   0.0   0.0   0.0   0.0       Salivary gland   11.0   4.5   7.0   0.0       Pituitary gland   0.0   0.0   7.7   28.9       Brain (fetal)   31.2   53.2   12.7   21.0       Brain (whole)   56.3   48.6   100.0   100.0       Brain (amygdala)   15.4   0.0   31.9   0.0       Brain (cerebellum)   10.0   19.6   0.0   25.2       Brain (hippocampus)   5.5   20.3   17.3   7.0       Brain (Substantia nigra)   54.3   80.7   49.3   31.6       Brain (thalamus)   26.2   58.2   55.5   72.2       Cerebral Cortex   5.6   0.0   14.3   0.0       Spinal cord   100.0   100.0   98.6   38.7       glio/astro U87-MG   13.0   0.0   0.0   0.0       glio/astro U-118-MG   4.2   7.2   0.0   0.0       astrocytoma SW1783   0.0   0.0   19.9   0.0       neuro*; met SK-N-AS   0.0   0.0   0.0   0.0       astrocytoma SF-539   12.3   6.5   0.0   5.4       astrocytoma SNB-75   0.0   0.0   0.0   3.9       glioma SNB-19   2.1   4.0   4.5   18.2       glioma U251   19.3   0.0   0.0   0.0       glioma SF-295   23.5   0.0   0.0   0.0       Heart (fetal)   0.0   0.0   0.0   0.0       Heart   12.4   10.7   0.0   0.0       Skeletal muscle (fetal)   0.0   0.0   0.0   0.0       Skeletal muscle   6.1   0.0   0.0   0.0       Bone marrow   0.0   0.0   0.0   0.0       Thymus   0.0   0.0   0.0   0.0       Spleen   0.0   0.0   0.0   0.0       Lymph node   6.7   0.0   0.0   0.0       Colorectal   10.7   4.9   0.0   0.0       Stomach   0.0   0.0   0.0   7.2       Small intestine   0.0   0.0   0.0   0.0       Colon ca. SW480   0.0   0.0   0.0   5.2       Colon ca.* SW620(SW480 met)   6.8   0.0   6.8   8.5       Colon ca. HT29   0.0   0.0   0.0   0.0       Colon ca. HCT-116   5.9   0.0   0.0   0.0       Colon ca. CaCo-2   0.0   6.6   0.0   0.0       Colon ca. tissue(ODO3866)   0.0   0.0   0.0   0.0       Colon ca. HCC-2998   0.0   0.0   0.0   0.0       Gastric ca.* (liver met) NCI-N87   0.0   6.7   0.0   8.0       Bladder   2.8   0.0   9.9   17.4       Trachea   0.0   6.4   0.0   0.0       Kidney   0.0   0.0   0.0   0.0       Kidney (fetal)   0.0   0.0   0.0   12.3       Renal ca. 786-0   0.0   3.4   0.0   0.0       Renal ca. A498   6.9   0.0   0.0   6.1       Renal ca. RXF 393   0.0   9.5   0.0   7.9       Renal ca. ACHN   0.0   0.0   3.1   6.4       Renal ca. UO-31   11.0   0.0   0.0   0.0       Renal ca. TK-10   4.9   0.0   0.0   0.0       Liver   8.0   0.0   0.0   0.0       Liver (fetal)   0.0   0.0   0.0   0.0       Liver ca. (hepatoblast) HepG2   0.0   0.0   0.0   0.0       Lung   11.0   0.0   0.0   0.0       Lung (fetal)   0.0   0.0   0.0   0.0       Lung ca. (small cell) LX-1   3.5   14.0   7.4   0.0       Lung ca. (small cell) NCI-H69   0.0   0.0   0.0   0.0       Lung ca. (s. cell var.) SHP-77   0.0   0.0   0.0   4.1       Lung ca. (large cell)NCI-H460   3.3   0.0   0.0   0.0       Lung ca. (non-sm. cell) A549   0.0   0.0   0.0   0.0       Lung ca. (non-s. cell) NCI-H23   5.3   14.4   8.2   5.6       Lung ca. (non-s. cell) HOP-62   0.0   0.0   0.0   0.0       Lung ca. (non-s. cl) NCI-H522   0.0   0.0   0.0   0.0       Lung ca. (squam.) SW 900   7.2   5.4   0.0   0.0       Lung ca. (squam.) NCI-H596   0.0   0.0   0.0   0.0       Mammary gland   0.0   0.0   7.7   0.0       Breast ca.* (pl. ef) MCF-7   4.7   0.0   0.0   0.0       Breast ca.* (pl. ef) MDA-MB-231   0.0   0.0   0.0   6.0       Breast ca.* (pl. ef) T47D   14.0   0.0   6.9   29.3       Breast ca. BT-549   0.0   0.0   0.0   0.0       Breast ca. MDA-N   5.2   12.6   18.0   0.0       Ovary   0.0   0.0   0.0   0.0       Ovarian ca. OVCAR-3   0.0   0.0   15.8   0.0       Ovarian ca. OVCAR-4   0.0   0.0   0.0   5.0       Ovarian ca. OVCAR-5   7.7   0.0   11.7   4.5       Ovarian ca. OVCAR-8   29.7   15.9   18.3   8.0       Ovarian ca. IGROV-1   17.6   0.0   0.0   0.0       Ovarian ca.* (ascites) SK-OV-3   0.0   0.0   0.0   6.4       Uterus   0.0   9.5   6.1   0.0       Placenta   51.8   21.5   43.2   39.0       Prostate   0.0   14.6   0.0   0.0       Prostate ca.* (bone met)PC-3   0.0   0.0   6.0   0.0       Testis   17.4   14.8   18.6   10.5       Melanoma Hs688(A).T   0.0   0.0   0.0   0.0       Melanoma* (met) Hs688(B).T   0.0   0.0   0.0   0.0       Melanoma UACC-62   0.0   3.7   0.0   6.9       Melanoma M14   6.4   35.6   12.1   0.0       Melanoma LOX IMVI   0.0   0.0   0.0   0.0       Melanoma* (met) SK-MEL-5   0.0   0.0   0.0   10.4       Adipose   0.0   0.0   0.0   0.0                    
     [0731]               TABLE MI                          Panel 2.2                             Rel. Exp. (%)   Rel. Exp. (%)           Ag2377, Run   Ag2607, Run       Tissue Name   174553776   175128152                                 Normal Colon   0.0   0.0       Colon cancer (OD06064)   15.3   0.0       Colon Margin (OD06064)   0.0   0.0       Colon cancer (OD06159)   0.0   0.0       Colon Margin (OD06159)   0.0   0.0       Colon cancer (OD06297-04)   0.0   0.0       Colon Margin (OD06297-05)   0.0   0.0       CC Gr.2 ascend colon (ODO3921)   0.0   0.0       CC Margin (ODO3921)   0.0   0.0       Colon cancer metastasis   0.0   0.0       (OD06104)       Lung Margin (OD06104)   0.0   0.0       Colon mets to lung (OD04451-01)   27.9   0.0       Lung Margin (OD04451-02)   32.5   0.0       Normal Prostate   0.0   0.0       Prostate Cancer (OD04410)   0.0   0.0       Prostate Margin (OD04410)   0.0   0.0       Normal Ovary   0.0   0.0       Ovarian cancer (OD06283-03)   10.7   0.0       Ovarian Margin (OD06283-07)   0.0   0.0       Ovarian Cancer 064008   0.0   24.1       Ovarian cancer (OD06145)   0.0   0.0       Ovarian Margin (OD06145)   34.9   0.0       Ovarian cancer (OD06455-03)   24.7   0.0       Ovarian Margin (OD06455-07)   9.9   0.0       Normal Lung   0.0   9.2       Invasive poor diff. lung adeno   12.7   0.0       (ODO4945-01       Lung Margin (ODO4945-03)   0.0   18.3       Lung Malignant Cancer (OD03126)   0.0   0.0       Lung Margin (OD03126)   0.0   0.0       Lung Cancer (OD05014A)   0.0   0.0       Lung Margin (OD05014B)   19.5   6.0       Lung cancer (OD06081)   25.9   9.3       Lung Margin (OD06081)   0.0   0.0       Lung Cancer (OD04237-01)   0.0   0.0       Lung Margin (OD04237-02)   0.0   11.0       Ocular Melanoma Metastasis   13.6   0.0       Ocular Melanoma Margin (Liver)   0.0   0.0       Melanoma Metastasis   0.0   2.6       Melanoma Margin (Lung)   0.0   0.0       Normal Kidney   17.9   0.0       Kidney Ca, Nuclear grade 2   0.0   0.0       (OD04338)       Kidney Margin (OD04338)   0.0   0.0       Kidney Ca Nuclear grade 1/2   15.3   0.0       (OD04339)       Kidney Margin (OD04339)   0.0   0.0       Kidney Ca, Clear cell type   0.0   0.0       (OD04340)       Kidney Margin (OD04340)   0.0   12.2       Kidney Ca, Nuclear grade 3   0.0   0.0       (OD04348)       Kidney Margin (OD04348)   0.0   20.7       Kidney malignant cancer   24.1   21.8       (OD06204B)       Kidney normal adjacent tissue   0.0   0.0       (OD06204E)       Kidney Cancer (OD04450-01)   0.0   9.5       Kidney Margin (OD04450-03)   0.0   0.0       Kidney Cancer 8120613   0.0   0.0       Kidney Margin 8120614   0.0   0.0       Kidney Cancer 9010320   0.0   0.0       Kidney Margin 9010321   0.0   0.0       Kidney Cancer 8120607   0.0   0.0       Kidney Margin 8120608   0.0   0.0       Normal Uterus   35.6   17.8       Uterine Cancer 064011   0.0   0.0       Normal Thyroid   0.0   0.0       Thyroid Cancer 064010   0.0   0.0       Thyroid Cancer A302152   0.0   0.0       Thyroid Margin A302153   0.0   0.0       Normal Breast   15.0   8.7       Breast Cancer (OD04566)   0.0   0.0       Breast Cancer 1024   84.1   36.1       Breast Cancer (OD04590-01)   0.0   0.0       Breast Cancer Mets   22.5   0.0       (OD04590-03)       Breast Cancer Metastasis   0.0   0.0       (OD04655-05)       Breast Cancer 064006   0.0   19.1       Breast Cancer 9100266   100.0   100.0       Breast Margin 9100265   9.9   0.0       Breast Cancer A209073   0.0   0.0       Breast Margin A2090734   14.6   0.0       Breast cancer (OD06083)   75.8   9.9       Breast cancer node metastasis   16.6   25.3       (OD06083)       Normal Liver   0.0   0.0       Liver Cancer 1026   0.0   0.0       Liver Cancer 1025   33.4   6.7       Liver Cancer 6004-T   0.0   0.0       Liver Tissue 6004-N   0.0   0.0       Liver Cancer 6005-T   0.0   0.0       Liver Tissue 6005-N   0.0   9.7       Liver Cancer 064003   0.0   0.0       Normal Bladder   0.0   0.0       Bladder Cancer 1023   0.0   0.0       Bladder Cancer A302173   0.0   0.0       Normal Stomach   0.0   0.0       Gastric Cancer 9060397   0.0   0.0       Stomach Margin 9060396   0.0   7.6       Gastric Cancer 9060395   33.2   7.6       Stomach Margin 9060394   0.0   0.0       Gastric Cancer 064005   0.0   0.0                    
     [0732]               TABLE MJ                          Panel 4D                             Rel. Exp. (%)   Rel. Exp. (%)           Ag2377, Run   Ag2607, Run       Tissue Name   164216614   164160833                                 Secondary Th1 act   27.4   14.3       Secondary Th2 act   36.3   0.0       Secondary Tr1 act   10.5   9.4       Secondary Th1 rest   0.0   0.0       Secondary Th2 rest   0.0   0.0       Secondary Tr1 rest   12.9   0.0       Primary Th1 act   0.0   0.0       Primary Th2 act   8.1   0.0       Primary Tr1 act   25.3   10.3       Primary Th1 rest   28.1   53.2       Primary Th2 rest   69.3   23.3       Primary Tr1 rest   13.3   15.1       CD45RA CD4 lymphocyte act   0.0   0.0       CD45RO CD4 lymphocyte act   34.4   7.3       CD8 lymphocyte act   8.7   9.2       Secondary CD8 lymphocyte rest   31.0   13.1       Secondary CD8 lymphocyte act   12.2   10.8       CD4 lymphocyte none   0.0   0.0       2ry Th1/Th2/Tr1_anti-CD95 CH11   25.9   14.6       LAK cells rest   28.5   33.2       LAK cells IL-2   0.0   9.9       LAK cells IL-2 + IL-12   20.0   0.0       LAK cells IL-2 + IFN gamma   12.2   10.0       LAK cells IL-2 + IL-18   9.4   0.0       LAK cells PMA/ionomycin   18.9   0.0       NK Cells IL-2 rest   25.5   17.4       Two Way MLR 3 day   31.2   5.4       Two Way MLR 5 day   0.0   12.0       Two Way MLR 7 day   10.6   0.0       PBMC rest   11.4   5.0       PBMC PWM   12.2   19.5       PBMC PHA-L   28.1   18.6       Ramos (B cell) none   13.9   18.8       Ramos (B cell) ionomycin   16.6   7.8       B lymphocytes PWM   15.7   12.9       B lymphocytes CD40L and IL-4   24.8   0.0       EOL-1 dbcAMP   13.7   7.4       EOL-1 dbcAMP PMA/ionomycin   6.2   0.0       Dendritic cells none   15.5   29.5       Dendritic cells LPS   10.7   17.0       Dendritic cells anti-CD40   11.5   5.6       Monocytes rest   0.0   0.0       Monocytes LPS   100.0   50.3       Macrophages rest   76.8   100.0       Macrophages LPS   8.0   8.5       HUVEC none   9.0   0.0       HUVEC starved   41.8   2.8       HUVEC IL-1beta   0.0   0.0       HUVEC IFN gamma   0.0   4.0       HUVEC TNF alpha + IFN   0.0   4.0       gamma       HUVEC TNF alpha + IL4   12.4   6.7       HUVEC IL-11   12.6   0.0       Lung Microvascular EC none   18.7   16.7       Lung Microvascular EC   0.0   12.9       TNFalpha + IL-1beta       Microvascular Dermal EC none   35.1   4.5       Microsvasular Dermal EC   8.2   10.7       TNFalpha + IL-1beta       Bronchial epithelium   0.0   0.0       TNFalpha + IL1beta       Small airway epithelium none   0.0   0.0       Small airway epithelium   0.0   10.7       TNFalpha + IL-1beta       Coronery artery SMC rest   12.2   0.0       Coronery artery SMC   0.0   0.0       TNFalpha + IL-1beta       Astrocytes rest   19.1   5.1       Astrocytes TNFalpha +   8.9   0.0       IL-1beta       KU-812 (Basophil) rest   0.0   0.0       KU-812 (Basophil)   13.9   5.6       PMA/ionomycin       CCD1106 (Keratinocytes) none   10.7   4.3       CCD1106 (Keratinocytes)   12.7   0.0       TNFalpha + IL-1beta       Liver cirrhosis   81.8   50.0       Lupus kidney   23.2   8.6       NCI-H292 none   0.0   3.7       NCI-H292 IL-4   44.4   0.0       NCI-H292 IL-9   7.0   0.0       NCI-H292 IL-13   0.0   3.9       NCI-H292 IFN gamma   11.0   1.9       HPAEC none   6.3   11.3       HPAEC TNF alpha + IL-1   24.3   4.5       beta       Lung fibroblast none   0.0   0.0       Lung fibroblast   0.0   0.0       TNF alpha + IL-1beta       Lung fibroblast IL-4   0.0   0.0       Lung fibroblast IL-9   0.0   3.3       Lung fibroblast IL-13   0.0   0.0       Lung fibroblast IFN gamma   0.0   5.1       Dermal fibroblast CCD1070 rest   2.4   15.7       Dermal fibroblast CCD1070   66.4   10.4       TNF alpha       Dermal fibroblast CCD1070   0.0   0.0       IL-1 beta       Dermal fibroblast IFN gamma   15.1   7.5       Dermal fibroblast IL-4   0.0   0.0       IBD Colitis 2   10.7   0.0       IBD Crohn&#39;s   0.0   0.0       Colon   0.0   0.0       Lung   0.0   4.5       Thymus   24.1   13.7       Kidney   44.4   17.7                    
     [0733]               TABLE MK                          Panel CNS_1                                     Rel. Exp. (%)   Rel. Exp. (%)               Ag2377, Run   Ag2377, Run           Tissue Name   171656285   182012511                                             BA4 Control   6.1   7.4           BA4 Control2   8.8   4.2           BA4 Alzheimer&#39;s2   0.0   7.1           BA4 Parkinson&#39;s   24.7   19.8           BA4 Parkinson&#39;s2   17.8   30.8           BA4 Huntington&#39;s   17.6   3.7           BA4 Huntington&#39;s2   8.1   0.0           BA4 PSP   38.2   12.2           BA4 PSP2   20.0   5.2           BA4 Depression   49.7   31.2           BA4 Depression2   14.2   18.0           BA7 Control   23.3   2.7           BA7 Control2   25.5   11.5           BA7 Alzheimer&#39;s2   18.9   4.4           BA7 Parkinson&#39;s   11.4   9.8           BA7 Parkinson&#39;s2   0.0   14.6           BA7 Huntington&#39;s   23.7   10.9           BA7 Huntington&#39;s2   42.9   26.8           BA7 PSP   30.8   14.6           BA7 PSP2   4.2   10.4           BA7 Depression   31.9   21.3           BA9 Control   2.0   4.4           BA9 Control2   16.7   24.7           BA9 Alzheimer&#39;s   0.0   6.6           BA9 Alzheimer&#39;s2   2.9   0.0           BA9 Parkinson&#39;s   11.3   15.2           BA9 Parkinson&#39;s2   7.9   4.2           BA9 Huntington&#39;s   39.8   14.5           BA9 Huntington&#39;s2   8.1   3.7           BA9 PSP   44.4   5.7           BA9 PSP2   0.0   0.0           BA9 Depression   15.1   5.9           BA9 Depression2   14.4   8.7           BA17 Control   47.0   30.4           BA17 Control2   28.7   5.4           BA17 Alzheimer&#39;s2   7.5   7.1           BA17 Parkinson&#39;s   38.2   68.3           BA17 Parkinson&#39;s2   24.0   9.3           BA17 Huntington&#39;s   36.1   13.8           BA17 Huntington&#39;s2   15.2   16.4           BA17 Depression   58.6   27.7           BA17 Depression2   65.5   60.3           BA17 PSP   0.0   21.0           BA17 PSP2   11.1   10.4           Sub Nigra Control   42.3   41.2           Sub Nigra Control2   29.5   3.6           Sub Nigra Alzheimer&#39;s2   28.5   12.6           Sub Nigra Parkinson&#39;s2   55.1   61.1           Sub Nigra Huntington&#39;s   100.0   100.0           Sub Nigra Huntington&#39;s2   17.3   21.2           Sub Nigra PSP2   9.7   5.4           Sub Nigra Depression   87.1   42.0           Sub Nigra Depression2   33.0   20.4           Glob Palladus Control   28.5   25.7           Glob Palladus Control2   25.2   15.2           Glob Palladus Alzheimer&#39;s   11.9   16.4           Glob Palladus Alzheimer&#39;s2   4.2   36.9           Glob Palladus Parkinson&#39;s   37.9   44.4           Glob Palladus Parkinson&#39;s2   9.0   26.1           Glob Palladus PSP   48.0   33.4           Glob Palladus PSP2   10.7   9.9           Glob Palladus Depression   40.9   39.5           Temp Pole Control   0.0   0.0           Temp Pole Control2   11.8   7.9           Temp Pole Alzheimer&#39;s   0.0   0.0           Temp Pole Alzheimer&#39;s2   0.0   3.4           Temp Pole Parkinson&#39;s   17.3   7.1           Temp Pole Parkinson&#39;s2   0.0   9.5           Temp Pole Huntington&#39;s   0.0   4.9           Temp Pole PSP   6.7   6.3           Temp Pole PSP2   0.0   0.0           Temp Pole Depression2   0.0   23.8           Cing Gyr Control   31.2   27.4           Cing Gyr Control2   16.8   24.5           Cing Gyr Alzheimer&#39;s   17.8   13.2           Cing Gyr Alzheimer&#39;s2   13.9   3.4           Cing Gyr Parkinson&#39;s   26.2   30.8           Cing Gyr Parkinson&#39;s2   24.8   25.9           Cing Gyr Huntington&#39;s   30.8   28.7           Cing Gyr Huntington&#39;s2   20.7   14.2           Cing Gyr PSP   90.1   76.3           Cing Gyr PSP2   0.0   20.3           Cing Gyr Depression   52.5   61.1           Cing Gyr Depression2   43.5   15.3                        
     [0734]               TABLE ML                          Panel CNS_1.1                                     Rel. Exp. (%)   Rel. Exp. (%)               Ag2377, Run   Ag2377, Run           Tissue Name   200060897   200061715                                             Cing Gyr Depression2   39.2   13.9           Cing Gyr Depression   35.8   23.2           Cing Gyr PSP2   6.2   2.8           Cing Gyr PSP   100.0   100.0           Cing Gyr Huntington&#39;s2   32.5   10.4           Cing Gyr Huntington&#39;s   27.4   8.8           Cing Gyr Parkinson&#39;s2   12.8   1.9           Cing Gyr Parkinson&#39;s   47.6   32.5           Cing Gyr Alzheimer&#39;s2   0.0   7.2           Cing Gyr Alzheimer&#39;s   13.8   3.6           Cing Gyr Control2   77.9   1.4           Cing Gyr Control   30.1   11.7           Temp Pole Depression2   0.0   14.8           Temp Pole PSP2   0.0   4.5           Temp Pole PSP   5.5   3.3           Temp Pole Huntington&#39;s   0.0   7.7           Temp Pole Parkinson&#39;s2   0.0   0.0           Temp Pole Parkinson&#39;s   27.5   4.9           Temp Pole Alzheimer&#39;s2   0.0   0.0           Temp Pole Alzheimer&#39;s   0.0   0.0           Temp Pole Control2   21.3   8.4           Temp Pole Control   0.0   0.0           Glob Palladus Depression   35.8   16.4           Glob Palladus PSP2   5.5   5.0           Glob Palladus PSP   23.7   8.6           Glob Palladus Parkinson&#39;s2   34.2   6.5           Glob Palladus Parkinson&#39;s   16.4   20.3           Glob Palladus Alzheimer&#39;s2   19.5   3.4           Glob Palladus Alzheimer&#39;s   24.3   6.7           Glob Palladus Control2   13.8   2.8           Glob Palladus Control   33.2   17.7           Sub Nigra Depression2   36.3   5.5           Sub Nigra Depression   52.5   10.4           Sub Nigra PSP2   12.4   15.9           Sub Nigra Huntington&#39;s2   8.7   5.9           Sub Nigra Huntington&#39;s   82.4   51.1           Sub Nigra Parkinson&#39;s2   34.9   12.5           Sub Nigra Alzheimer&#39;s2   34.2   15.0           Sub Nigra Control2   6.3   5.3           Sub Nigra Control   58.6   10.2           BA17 Depression2   39.2   9.3           BA17 Depression   43.5   50.7           BA17 PSP2   5.3   11.8           BA17 PSP   4.2   13.1           BA17 Huntington&#39;s2   17.8   10.1           BA17 Huntington&#39;s   36.9   6.9           BA17 Parkinson&#39;s2   19.2   12.2           BA17 Parkinson&#39;s   37.4   19.1           BA17 Alzheimer&#39;s2   7.7   0.0           BA17 Control2   35.8   20.0           BA17 Control   35.1   22.7           BA9 Depression2   8.6   3.8           BA9 Depression   0.0   14.1           BA9 PSP2   3.6   12.4           BA9 PSP   48.6   18.3           BA9 Huntington&#39;s2   6.9   5.0           BA9 Huntington&#39;s   59.0   8.4           BA9 Parkinson&#39;s2   0.0   2.5           BA9 Parkinson&#39;s   7.9   0.0           BA9 Alzheimer&#39;s2   0.0   0.0           BA9 Alzheimer&#39;s   0.0   0.0           BA9 Control2   26.4   12.2           BA9 Control   15.1   0.0           BA7 Depression   29.3   11.1           BA7 PSP2   28.7   2.9           BA7 PSP   7.0   6.6           BA7 Huntington&#39;s2   18.6   23.7           BA7 Huntington&#39;s   11.3   6.7           BA7 Parkinson&#39;s2   0.0   0.0           BA7 Parkinson&#39;s   9.5   1.2           BA7 Alzheimer&#39;s2   19.6   0.0           BA7 Control2   25.3   2.4           BA7 Control   10.1   9.6           BA4 Depression2   27.5   15.9           BA4 Depression   10.8   15.6           BA4 PSP2   15.2   17.0           BA4 PSP   11.3   10.7           BA4 Huntington&#39;s2   0.0   0.0           BA4 Huntington&#39;s   0.0   3.8           BA4 Parkinson&#39;s2   18.7   11.7           BA4 Parkinson&#39;s   54.0   3.2           BA4 Alzheimer&#39;s2   6.2   0.0           BA4 Control2   0.0   4.2           BA4 Control   35.6   4.7                        
     [0735] CNS_neurodegeneration_v1.0 Summary: Ag2610/Ag2607/Ag2377 The CG50303-03 gene is expressed more highly in the temporal cortex of Alzheimer&#39;s diseased brain than in control brain without amyloid plaques, which are diagnostic and potentially causative of Alzheimer&#39;s disease. The CG50303-03 gene encodes a protein with homology to GPCRs. GPCRs are readily targetable with drugs, and regulate many specific brain processes, including signaling processes, that are currently the target of FDA-approved pharmaceuticals that treat Alzheimer&#39;s disease, such as the cholinergic system. The major mechanisms proposed for AbetaP-induced cytotoxicity involve the loss of Ca2+ homeostasis and the generation of reactive oxygen species (ROS). The changes in Ca2+ homeostasis could be the result of changes in G-protein-driven releases of second messengers. Thus, targeting this class of molecule can have therapeutic potential in Alzheimer&#39;s disease treatment. In particular, the increased CG50303-03 gene expression in brains affected by Alzheimer&#39;s indicates potential therapeutic value to drugs that target this GPCR.  
     [0736] See Perrine K, Dogali M, Fazzini E, Sterio D, Kolodny E, Eidelberg D, Devinsky O, Beric A.Cognitive functioning after pallidotomy for refractory Parkinson&#39;s disease. J Neurol Neurosurg Psychiatry 1998 Aug;65(2):150-4. PMID: 9703163; and Kourie J I. Mechanisms of amyloid beta protein-induced modification in ion transport systems: implications for neurodegenerative diseases. Cell Mol Neurobiol 2001 June; 21(3):173-213 PMID: 11569534.  
     [0737] Panel 1.2 Summary: Ag1501 The CG50303-03 gene is expressed at moderate levels throughout many of the samples in this panel. Highest expression is detected in an ovarian cancer cell line (CT=30.7). In addition, this gene is overexpressed in all six ovarian cancer cell lines present in this panel when compared to expression in normal ovary. The CG50303-03 gene is also moderately expressed in cell lines derived from melanoma, breast cancer, and lung cancer. Thus, the expression of this gene could be used to distinguish these cell lines from other tissue samples. In addition, therapeutic modulation of the CG50303-03 gene or its protein product, through the use of small molecule drugs or antibodies, might be useful in the treatment of ovarian cancer, breast cancer, lung cancer or melanoma.  
     [0738] Among tissues involved in metabolic function, the CG50303-03 gene is moderately expressed in the adrenal gland, heart, skeletal muscle, and adult liver. Interestingly, CG50303-03 gene expression is much lower in fetal liver and heart tissues than in the corresponding adult tissues. Thus, expression of the CG50303-03 gene could be used to differentiate between adult and fetal tissues derived from the heart and liver. Furthermore, this gene or its protein product may be important in the pathogenesis and/or treatment of disease in any or all of the above-named tissues.  
     [0739] There is widespread moderate expression of the CG50303-03 gene across many of the samples derived from the CNS, including the amygdala, cerebellum, hippocampus, thalamus, cerebral cortex, and spinal cord. Please see CNS_neurodegeneration panel_v1.0 summary for description of the potential role of this gene in the treatment of CNS disorders.  
     [0740] Panel 1.3D Summary: Ag2610/Ag2607/Ag1585/Ag2377 Expression of the CG50303-03 gene appears to be limited to tissues involved in central nervous system function on this panel. Specifically, low but significant expression is detected in the thalamus, substantia nigra, spinal cord and fetal brain.  
     [0741] Panel 2.2 Summary: Ag2377/Ag2607 Expression of the CG50303-03 gene is highest in a sample derived from a breast cancer sample (CTs=34-34.7). Thus, the expression of this gene could be used to distinguish breast cancer samples from other samples and as a diagnostic marker for the presence of breast cancer. Furthermore, therapeutic modulation of the CG50303-03 gene or the activity of its protein product, through the use of small molecule drugs or antibodies, might be effective in the treatment of breast cancer. Ag2610/Ag1585 Expression of the CG50303-03 gene is low/undetectable (Ct values&gt;35) in all samples on this panel.  
     [0742] Panel 4D Summary: Ag2607/Ag2377 Two experiments with two different probe and primer sets show the CG50303-03 gene is up regulated in LPS-stimulated monocytes (CTw=32-34). The putative GPCR encoded by this gene may therefore be involved in the activation of monocytes in their function as antigen-presenting cells. This suggests that antibodies or small molecule therapeutics that block the function of this membrane protein may be useful as anti-inflammatory therapeutics for the treatment of autoimmune and inflammatory diseases. Furthermore, antibodies or small molecule therapeutics that stimulate the function of this GPCR may be useful therapeutics for the treatment of immunosupressed individuals. Please note that data from one experiment with probe and primer set Ag2610 showed low/undetectable expression in all the samples on this panel (CTs&gt;35).  
     [0743] Panel CNS — 1 Summary: Ag2377 Two experiments with the same probe and primer set produce results that are in very good agreement. Expression of the CG50303-03 gene is highest in the substantia nigra of a Huntington&#39;s disease patient, indicating that this gene may participate in the genetic dysregulation associated with the neurodegeneration that occurs in this brain region. The substantia nigra is also critical to the progression of Parkinson&#39;s disease neurodegeneration. Thus, pharmacological targeting of the GPCR encoded by the CG50303-03 gene may help counter this genetic dysregulation and contribute to the restoration of normal function in Huntington&#39;s disease as well as potentially Parkinson&#39;s disease patients. Pharmacological modulation of GPCR signaling systems is the mechanism by which powerful depression therapies, such as SSRIs, exert their effect. Please note that a third experiment with the probe and primer set Ag1585 showed low/undetectable expression in all the samples on this panel (CTs&gt;35).  
     [0744] Panel CNS — 1.1 Summary: Ag2377 In two experiments using the same probe and primer, highest expression of the CG50303-03 gene is seen in the cingulate gyrus of patients with para supranuclear palsy PSP (CTs=32) and depression. This observation indicates that targeting this GPCR could have therapeutic value in the treatment of these diseases.  
     [0745] N. CG54092-01: Tandem Acid-Sensitive Potassium Channel Task5.  
     [0746] Expression of gene CG54092-01 was assessed using the primer-probe sets Ag241 and Ag3074, described in Tables NA and NB. Results of the RTQ-PCR runs are shown in Tables NC, ND, NE, NF, NG, NH and NI.  
               TABLE NA                          Probe Name Ag241                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-cagggtcgaatctggaatgg-3′   20   1009   190               Probe   TET-5′-tctggcttcagctatcagggcaccc-3′-TAMRA   25   1034   191               Reverse   5′-cccgtcatccgtttccaat-3′   19   1068   192                  
 
     [0747]               TABLE NB                          Probe Name Ag3074                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-gctccttctacttcgccatc-3′   20   245   193               Probe   TET-5′-tcatcactaccatcgagtacgqccac-3′-TAMRA   26   269   194               Reverse   5′-acatgcagaagaccttgcc-3′   19   316   195                    
     [0748]               TABLE NC                          AI.05 chondrosarcoma                                 Rel.               Exp.(%)               Ag3074,               Run           Tissue Name   306941363                                         138353_PMA (18 hrs)   18.0           138352_IL-1beta + Oncostatin M   82.9           (18 hrs)           138351_IL-1beta + TNFa(18 hrs)   38.2           138350_IL-1beta (18 hrs)   51.4           138354_Untreated-complete   17.6           medium (18 hrs)           138347_PMA (6 hrs)   41.8           138346_IL-1beta + Oncostatin M   100.0           (6 hrs)           138345_IL-1beta + TNFa (6 hrs)   13.4           138344 IL-lbeta(6 hrs)   118.0           138349_Untreated-serum starved   53.2           (6 hrs)           138348_Untreated-complete   17.1           medium (6 hrs)                        
     [0749]               TABLE ND                          AI_comprehensive panel_v1.0                                 Rel. Exp. (%)               Ag3074,               Run           Tissue Name   248429496                                         110967 COPD-F   18.9           110980 COPD-F   27.9           110968 COPD-M   12.5           110977 COPD-M   48.0           110989 Emphysema-F   29.1           110992 Emphysema-F   26.2           110993 Emphysema-F   25.9           110994 Emphysema-F   10.4           110995 Emphysema-F   17.4           110996 Emphysema-F   4.8           110997 Asthma-M   9.0           111001 Asthma-F   24.7           111002 Asthma-F   39.5           111003 Atopic Asthma-F   59.9           111004 Atopic Asthma-F   88.9           111005 Atopic Asthma-F   51.8           111006 Atopic Asthma-F   13.5           111417 Allergy-M   73.2           112347 Allergy-M   0.0           112349 Normal Lung-F   1.0           112357 Normal Lung-F   21.6           112354 Normal Lung-M   33.4           112374 Crohns-F   5.7           112389 Match Control Crohns-F   4.9           112375 Crohns-F   3.0           112732 Match Control Crohns-F   0.0           112725 Crohns-M   1.7           112387 Match Control Crohns-M   18.9           112378 Crohns-M   0.0           112390 Match Control Crohns-M   21.6           112726 Crohns-M   70.2           112731 Match Control Crohns-M   13.6           112380 Ulcer Col-F   27.2           112734 Match Control Ulcer Col-F   7.4           112384 Ulcer Col-F   22.8           112737 Match Control Ulcer Col-F   23.8           112386 Ulcer Col-F   5.0           112738 Match Control Ulcer Col-F   2.3           112381 Ulcer Col-M   3.0           112735 Match Control Ulcer Col-M   1.5           112382 Ulcer Col-M   11.2           112394 Match Control Ulcer Col-M   3.5           112383 Ulcer Col-M   34.9           112736 Match Control Ulcer Col-M   6.1           112423 Psoriasis-F   6.6           112427 Match Control Psoriasis-F   36.1           112418 Psoriasis-M   24.3           112723 Match Control Psoriasis-M   27.0           112419 Psoriasis-M   23.3           112424 Match Control Psoriasis-M   7.0           112420 Psoriasis-M   47.0           112425 Match Control Psoriasis-M   47.6           104689 (MF) OA Bone-Backus   10.7           104690 (MF) Adj “Normal” Bone-Backus   18.0           104691 (MF) OA Synovium-Backus   34.6           104692 (BA) OA Cartilage-Backus   3.0           104694 (BA) OA Bone-Backus   36.3           104695 (BA) Adj “Normal” Bone-Backus   26.4           104696 (BA) OA Synovium-Backus   100.0           104700 (SS) OA Bone-Backus   6.9           104701 (SS) Adj “Normal” Bone-Backus   18.2           104702 (SS) OA Synovium-Backus   41.2           117093 OA Cartilage Rep7   37.9           112672 OA Bone5   63.7           112673 OA Synovium5   25.5           112674 OA Synovial Fluid cells5   30.6           117100 OA Cartilage Rep14   23.0           112756 OA Bone9   1.7           112757 OA Synovium9   0.0           112758 OA Synovial Fluid Cells9   4.8           117125 RA Cartilage Rep2   22.1           113492 Bone2 RA   3.3           113493 Synovium2 RA   0.0           113494 Syn Fluid Cells RA   10.8           113499 Cartilage4 RA   10.4           113500 Bone4 RA   0.0           113501 Synovium4 RA   3.3           113502 Syn Fluid Cells4 RA   2.9           113495 Cartilage3 RA   2.9           113496 Bone3 RA   9.7           113497 Synovium3 RA   1.2           113498 Syn Fluid Cells3 RA   6.7           117106 Normal Cartilage Rep20   18.0           113663 Bone3 Normal   0.0           113664 Synovium3 Normal   0.0           113665 Syn Fluid Cells3 Normal   0.0           117107 Normal Cartilage Rep22   4.6           113667 Bone4 Normal   8.8           113668 Synovium4 Normal   5.5           113669 Syn Fluid Cells4 Normal   9.2                        
     [0750]               TABLE NE                          Panel 1.3D                                 Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)           Ag241, Run   Ag241, Run   Ag3074, Run       Tissue Name   155695586   163728044   163724451                                     Liver   0.3   1.7   6.9       adenocarcinoma       Pancreas   0.5   1.2   0.6       Pancreatic ca.   0.4   0.0   0.0       CAPAN 2       Adrenal gland   1.4   1.3   0.6       Thyroid   4.1   4.4   19.8       Salivary gland   1.0   0.1   1.3       Pituitary gland   2.9   2.0   0.6       Brain (fetal)   0.3   0.0   0.0       Brain (whole)   0.1   0.3   0.9       Brain   0.4   0.1   0.0       (amygdala)       Brain   0.0   0.0   0.0       (cerebellum)       Brain   1.3   0.0   0.0       (hippocampus)       Brain   0.2   0.0   0.4       (substantia       nigra)       Brain   0.2   0.0   1.2       (thalamus)       Cerebral Cortex   0.1   2.3   1.5       Spinal cord   0.6   0.9   0.7       glio/astro   0.2   0.4   0.6       U87-MG       glio/astro   7.8   2.9   4.3       U-118-MG       astrocytoma   0.0   0.0   0.0       SW1783       neuro*; met   0.6   0.0   0.0       SK-N-AS       astrocytoma   0.1   0.6   0.0       SF-539       astrocytoma   2.3   0.6   0.0       SNB-75       glioma SNB-19   0.0   0.5   0.7       glioma U251   0.0   0.3   0.0       glioma SF-295   0.2   0.4   0.6       Heart (fetal)   0.6   0.0   0.3       Heart   0.2   1.5   6.5       Skeletal muscle   1.4   2.6   1.7       (fetal)       Skeletal muscle   0-5   0.4   0.0       Bone marrow   0.0   0.0   0.0       Thymus   0.0   0.8   2.2       Spleen   0.0   0.0   0.7       Lymph node   0.4   0.0   0.0       Colorectal   0.9   0.4   1.0       Stomach   1.5   0.7   0.7       Small intestine   0.4   0.3   0.3       Colon ca.   1.3   0.6   0.6       SW480       Colon ca.*   0.2   1.3   0.0       SW620(SW480 met)       Colon ca. HT29   0.0   0.0   0.0       Colon ca.   0.0   0.0   0.0       HCT-116       Colon ca.   3.0   4.7   2.4       CaCo-2       Colon ca.   1.5   3.0   5.4       tissue(ODO3866)       Colon ca.   2.4   1.6   1.0       HCC-2998       Gastric ca.*   100.0   100.0   100.0       (liver met)       NCI-N87       Bladder   3.0   5.8   12.9       Trachea   4.4   3.1   9.0       Kidney   0.1   0.4   1.6       Kidney (fetal)   1.0   0.0   0.4       Renal ca.   0.0   0.0   0.0       786-0       Renal ca.   0.4   0.0   0.0       A498       Renal ca.   0.1   0.4   2.1       RXF 393       Renal ca.   14.0   23.5   28.7       ACHN       Renal ca.   0.0   0.0   0.0       UO-31       Renal ca.   0.0   0.0   0.0       TK-10       Liver   0.0   0.0   0.0       Liver (fetal)   0.0   0.0   0.0       Liver ca.   0.0   0.0   0.0       (hepatoblast) HepG2       Lung   3.8   0.7   1.4       Lung (fetal)   0.0   0.4   0.3       Lung ca.   0.2   0.0   0.9       (small cell)       LX-1       Lung ca.   2.7   1.4   0.3       (small cell)       NCI-H69       Lung ca.   0.0   0.0   0.0       (s. cell var.)       SHP-77       Lung ca.   0.2   0.6   0.0       (large cell)NCI-       H460       Lung ca.   4.1   1.2   2.5       (non-sm. cell)       A549       Lung ca.   39.0   50.0   45.1       (non-s. cell)       NCI-H23       Lung ca.   0.2   0.0   0.0       (non-s. cell)       HOP-62       Lung ca.   0.2   0.4   0.3       (non-s. cl)       NCI-H522       Lung ca.   0.8   1.1   0.0       (squam.) SW       900       Lung ca.   0.1   0.9   1.0       (squam.)       NCI-H596       Mammary gland   3.0   1.6   0.4       Breast ca.*   43.5   73.2   43.8       (pl. ef) MCF-7       Breast ca.*   0.0   0.0   0.0       (pl. ef)       MDA-MB-231       Breast ca.*   9.2   9.2   24.0       (pl. ef) T47D       Breast ca.   0.8   0.0   0.4       BT-549       Breast ca.   0.1   0.0   0.0       MDA-N       Ovary   3.3   6.5   11.0       Ovarian ca.   11.6   18.7   19.1       OVCAR-3       Ovarian ca.   10.4   5.7   9.0       OVCAR-4       Ovarian ca.   1.3   2.3   3.4       OVCAR-5       Ovarian ca.   7.9   9.3   12.8       OVCAR-8       Ovarian ca.   0.1   0.0   0.0       IGROV-1       Ovarian ca.*   3.8   2.8   5.1       (ascites)       SK-OV-3       Uterus   2.1   1.3   3.9       Placenta   0.0   0.7   0.5       Prostate   0.6   0.4   7.2       Prostate ca.*   17.3   21.3   33.9       (bone       met)PC-3       Testis   7.1   3.2   9.2       Melanoma   0.0   0.0   0.0       Hs688(A).T       Melanoma*   0.0   0.0   1.4       (met)       Hs688(B).T       Melanoma   0.0   0.5   0.0       UACC-62       Melanoma   0.0   0.0   0.4       M14       Melanoma   0.0   0.0   0.0       LOX IMVI       Melanoma*   0.0   0.0   0.0       (met)       SK-MEL-5       Adipose   2.3   2.2   2.6                    
     [0751]               TABLE NF                          Panel 2D                                 Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)           Ag241, Run   Ag241, Run   Ag3074, Run       Tissue Name   155695603   163578011   163578433                                     Normal Colon   3.7   6.9   2.1       CC Well to   6.0   6.3   1.9       Mod Diff       (ODO3866)       CC Margin   0.7   0.0   0.9       (ODO3866)       CC Gr.2   0.0   0.0   0.0       rectosigmoid       (ODO3868)       CC Margin   0.0   0.0   0.0       (ODO3868)       CC Mod Diff   0.0   0.0   0.0       (ODO3920)       CC Margin   0.0   0.8   0.0       (ODO3920)       CC Gr.2   18.7   14.1   7.1       ascend colon       (ODO3921)       CC Margin   1.1   0.6   1.3       (ODO3921)       CC from   0.4   3.8   0.6       Partial       Hepatectomy       (ODO4309)       Mets       Liver Margin   0.0   0.0   0.0       (ODO4309)       Colon mets   1.0   3.5   0.0       to lung       (OD04451-01)       Lung Margin   2.4   1.6   0.3       (OD04451-02)       Normal   3.1   15.8   10.8       Prostate       6546-1       Prostate   0.7   2.0   2.1       Cancer       (OD04410)       Prostate   3.5   2.2   1.2       Margin       (OD04410)       Prostate   1.6   1.4   1.4       Cancer       (OD04720-01)       Prostate   5.3   5.8   6.5       Margin       (OD04720-02)       Normal Lung   2.3   3.1   2.0       061010       Lung Met   1.7   1.2   0.2       to Muscle       (ODO4286)       Muscle   5.6   3.5   5.2       Margin       (ODO4286)       Lung   12.8   8.8   13.9       Malignant       Cancer       (OD03126)       Lung Margin   2.0   2.9   2.9       (OD03126)       Lung Cancer   3.1   2.0   2.7       (OD04404)       Lung Margin   11.0   9.6   4.3       (OD04404)       Lung Cancer   0.0   0.0   0.0       (OD04565)       Lung Margin   2.4   1.7   0.5       (OD04565)       Lung Cancer   0.0   0.0   1.4       (OD04237-01)       Lung Margin   5.4   5.6   2.7       (OD04237-02)       Ocular Mel   3.1   0.9   0.7       Met to Liver       (ODO4310)       Liver Margin   0.0   0.0   0.8       (ODO4310)       Melanoma   12.9   12.9   13.9       Mets to Lung       (OD04321)       Lung Margin   7.5   8.4   8.8       (OD04321)       Normal   2.3   0.0   1.1       Kidney       Kidney Ca,   2.4   6.0   1.5       Nuclear       grade 2       (OD04338)       Kidney   2.3   2.9   1.5       Margin       (OD04338)       Kidney Ca   2.5   7.3   0.8       Nuclear       grade 1/2       (OD04339)       Kidney   1.6   3.9   1.4       Margin       (OD04339)       Kidney Ca,   0.9   0.0   0.2       Clear cell       type       (OD04340)       Kidney   4.6   3.7   1.7       Margin       (OD04340)       Kidney Ca,   0.0   0.2   1.1       Nuclear       grade 3       (OD04348)       Kidney   2.2   0.7   2.4       Margin       (OD04348)       Kidney   0.0   0.7   0.1       Cancer       (OD04622-01)       Kidney   5.6   5.8   4.7       Margin       (OD04622-03)       Kidney   27.0   16.3   9.0       Cancer       (OD04450-01)       Kidney   0.0   1.0   1.4       Margin       (OD04450-03)       Kidney   0.6   1.7   2.2       Cancer       8120607       Kidney   1.3   1.2   2.3       Margin       8120608       Kidney   0.0   0.0   0.0       Cancer       8120613       Kidney   3.2   0.0   1.7       Margin       8120614       Kidney   5.1   3.3   2.9       Cancer       9010320       Kidney   6.2   2.6   3.6       Margin       9010321       Normal   6.3   10.8   8.8       Uterus       Uterus   3.5   1.1   3.5       Cancer       064011       Normal   18.3   10.5   5.8       Thyroid       Thyroid   21.8   23.0   15.6       Cancer       064010       Thyroid   15.8   15.4   12.1       Cancer       A302152       Thyroid   6.0   8.0   5.5       Margin       A302153       Normal   8.5   12.7   4.8       Breast       Breast   71.7   79.6   43.2       Cancer       (OD04566)       Breast   88.3   55.9   100.0       Cancer       (OD04590-01)       Breast Cancer   66.9   59.5   80.1       Mets       (OD04590-03)       Breast Cancer   100.0   100.0   82.9       Metastasis       (OD04655-05)       Breast Cancer   6.0   7.9   2.8       064006       Breast Cancer   13.1   4.1   3.6       1024       Breast Cancer   90.8   80.7   69.7       9100266       Breast   16.8   18.6   7.1       Margin       9100265       Breast Cancer   4.2   0.3   2.0       A209073       Breast   4.5   2.0   3.1       Margin       A209073       Normal Liver   0.0   0.0   0.0       Liver Cancer   0.0   0.0   0.0       064003       Liver Cancer   0.0   0.0   0.8       1025       Liver Cancer   4.3   7.6   3.4       1026       Liver Cancer   0.0   0.0   0.4       6004-T       Liver Tissue   0.7   0.0   0.0       6004-N       Liver Cancer   2.6   7.4   3.5       6005-T       Liver Tissue   0.5   0.6   0.6       6005-N       Normal   12.9   15.0   8.3       Bladder       Bladder   0.4   1.6   0.2       Cancer 1023       Bladder   0.7   2.9   0.0       Cancer       A302173       Bladder   9.6   19.5   5.6       Cancer       (OD04718-01)       Bladder   5.3   10.2   6.5       Normal       Adjacent       (OD04718-03)       Normal Ovary   5.3   5.7   9.4       Ovarian   70.7   62.9   67.8       Cancer       064008       Ovarian   9.9   4.8   5.3       Cancer       (OD04768-07)       Ovary Margin   1.2   6.2   4.0       (OD04768-08)       Normal   2.1   1.9   0.9       Stomach       Gastric   2.5   2.9   0.4       Cancer       9060358       Stomach   0.6   2.4   1.2       Margin       9060359       Gastric   8.4   6.3   2.5       Cancer       9060395       Stomach   4.0   2.5   0.9       Margin       9060394       Gastric   0.4   1.9   0.7       Cancer       9060397       Stomach   1.5   1.2   1.0       Margin       9060396       Gastric   4.5   3.0   2.6       Cancer       064005                    
     [0752]               TABLE NG                          Panel 3D                         Rel. Exp. (%)           Ag241,           Run       Tissue Name   165022800                             Daoy- Medulloblastoma   0.8       TE671- Medulloblastoma   2.1       D283 Med- Medulloblastoma   0.0       PFSK-1- Primitive   0.0       Neuroectodermal       XF-498- CNS   0.0       SNB-78- Glioma   0.0       SF-268- Glioblastoma   0.0       T98G- Glioblastoma   0.0       SK-N-SH- Neuroblastoma (metastasis)   1.8       SF-295- Glioblastoma   0.0       Cerebellum   1.1       Cerebellum   0.0       NCI-H292- Mucoepidermoid lung carcinoma   6.8       DMS-114- Small cell lung cancer   0.8       DMS-79- Small cell lung cancer   9.5       NCI-H146- Small cell lung cancer   0.7       NCI-H526- Small cell lung cancer   4.0       NCI-N417- Small cell lung cancer   0.8       NCI-H82- Small cell lung cancer   0.0       NCI-H157- Squamous cell lung cancer (metastasis)   0.0       NCI-H1155- Large cell lung cancer   0.0       NCI-H1299- Large cell lung cancer   0.0       NCI-H727- Lung carcinoid   1.0       NCI-UMC-11- Lung carcinoid   0.0       LX-1- Small cell lung cancer   0.0       Colo-205- Colon cancer   0.0       KM12- Colon cancer   0.0       KM20L2- Colon cancer   1.8       NCI-H716- Colon cancer   0.0       SW-48- Colon adenocarcinoma   0.0       SW1116- Colon adenocarcinoma   0.0       LS 174T- Colon adenocarcinoma   14.4       SW-948- Colon adenocarcinoma   0.0       SW-480- Colon adenocarcinoma   0.6       NCI-SNU-5- Gastric carcinoma   1.4       KATO III- Gastric carcinoma   0.0       NCI-SNU-16- Gastric carcinoma   0.0       NCI-SNU-1- Gastric carcinoma   0.0       RF-1- Gastric adenocarcinoma   0.0       RF-48- Gastric adenocarcinoma   0.0       MKN-45- Gastric carcinoma   18.2       NCI-N87- Gastric carcinoma   12.2       OVCAR-5- Ovarian carcinoma   0.0       RL95-2- Uterine carcinoma   0.0       HelaS3- Cervical adenocarcinoma   100.0       Ca Ski- Cervical epidermoid carcinoma (metastasis)   0.0       ES-2- Ovarian clear cell carcinoma   0.0       Ramos- Stimulated with PMA/ionomycin 6 h   0.0       Ramos- Stimulated with PMA/ionomycin 14 h   0.0       MEG-01- Chronic myelogenous leukemia   0.0       (megokaryoblast)       Raji- Burkitt&#39;s lymphoma   0.0       Daudi- Burkitt&#39;s lymphoma   0.0       U266- B-cell plasmacytoma   6.8       CA46- Burkitt&#39;s lymphoma   0.0       RL- non-Hodgkin&#39;s B-cell lymphoma   0.0       JM1- pre-B-cell lymphoma   0.0       Jurkat- T cell leukemia   0.0       TF-1- Erythroleukemia   0.0       HUT 78- T-cell lymphoma   0.0       U937- Histiocytic lymphoma   0.0       KU-812- Myelogenous leukemia   0.0       769-P- Clear cell renal carcinoma   0.0       Caki-2- Clear cell renal carcinoma   0.0       SW 839- Clear cell renal carcinoma   0.0       Rhabdoid kidney tumor   28.1       Hs766T- Pancreatic carcinoma (LN metastasis)   0.4       CAPAN-1- Pancreatic adenocarcinoma (liver metastasis)   2.0       SU86.86- Pancreatic carcinoma (liver metastasis)   0.7       BxPC-3- Pancreatic adenocarcinoma   1.7       HPAC- Pancreatic adenocarcinoma   1.4       MIA PaCa-2- Pancreatic carcinoma   4.6       CFPAC-1- Pancreatic ductal adenocarcinoma   0.0       PANC-1- Pancreatic epithelioid ductal carcinoma   15.7       T24- Bladder carcinma (transitional cell)   0.0       5637- Bladder carcinoma   2.3       HT-1197- Bladder carcinoma   0.0       UM-UC-3- Bladder carcinma (transitional cell)   0.0       A204- Rhabdomyosarcoma   0.0       HT-1080- Fibrosarcoma   0.0       MG-63- Osteosarcoma   0.0       SK-LMS-1- Leiomyosarcoma (vulva)   7.6       SJRH30- Rhabdomyosarcoma (met to bone marrow)   0.0       A431- Epidermoid carcinoma   0.0       WM266-4- Melanoma   19.1       DU 145- Prostate carcinoma (brain metastasis)   0.0       MDA-MB-468- Breast adenocarcinoma   0.5       SCC-4- Squamous cell carcinoma of tongue   0.0       SCC-9- Squamous cell carcinoma of tongue   0.0       SCC-15- Squamous cell carcinoma of tongue   0.0       CAL 27- Squamous cell carcinoma of tongue   2.0                    
     [0753]               TABLE NH                          Panel 4.1D                         Rel. Exp. (%)           Ag3074,           Run       Tissue Name   248389309                             Secondary Th1 act   0.0       Secondary Th2 act   1.6       Secondary Tr1 act   3.3       Secondary Th1 rest   0.0       Secondary Th2 rest   0.0       Secondary Tr1 rest   0.0       Primary Th1 act   5.2       Primary Th2 act   0.0       Primary Tr1 act   0.0       Primary Th1 rest   0.0       Primary Th2 rest   0.0       Primary Tr1 rest   0.0       CD45RA CD4 lymphocyte act   5.6       CD45RO CD4 lymphocyte act   4.0       CD8 lymphocyte act   0.0       Secondary CD8 lymphocyte rest   0.0       Secondary CD8 lymphocyte act   0.0       CD4 lymphocyte none   0.0       2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0       LAK cells rest   0.0       LAK cells IL-2   0.0       LAK cells IL-2 + IL-12   0.0       LAK cells IL-2 + IFN gamma   0.0       LAK cells IL-2 + IL-18   0.0       LAK cells PMA/ionomycin   0.0       NK Cells IL-2 rest   0.0       Two Way MLR 3 day   0.0       Two Way MLR 5 day   0.0       Two Way MLR 7 day   0.0       PBMC rest   0.0       PBMC PWM   0.0       PBMC PHA-L   3.4       Ramos (B cell) none   0.0       Ramos (B cell) ionomycin   0.0       B lymphocytes PWM   0.0       B lymphocytes CD40L and IL-4   1.0       EOL-1 dbcAMP   0.0       EOL-1 dbcAMP PMA/ionomycin   0.0       Dendritic cells none   0.0       Dendritic cells LPS   0.0       Dendritic cells anti-CD40   0.0       Monocytes rest   0.0       Monocytes LPS   0.0       Macrophages rest   0.0       Macrophages LPS   0.0       HUVEC none   0.0       HUVEC starved   0.0       HUVEC IL-1beta   0.0       HUVEC IFN gamma   0.0       HUVEC TNF alpha + IFN gamma   0.0       HUVEC TNF alpha + IL4   0.0       HUVEC IL-11   0.0       Lung Microvascular EC none   0.0       Lung Microvascular EC TNFalpha + IL-1beta   0.0       Microvascular Dermal EC none   0.0       Microsvasular Dermal EC TNFalpha + IL-1beta   0.0       Bronchial epithelium TNFalpha + IL1beta   0.0       Small airway epithelium none   0.0       Small airway epithelium TNFalpha + IL-1beta   0.0       Coronery artery SMC rest   0.0       Coronery artery SMC TNFalpha + IL-1beta   0.0       Astrocytes rest   0.0       Astrocytes TNFalpha + IL-1beta   5.8       KU-812 (Basophil) rest   0.0       KU-812 (Basophil) PMA/ionomycin   0.0       CCD1106 (Keratinocytes) none   0.0       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   0.0       Liver cirrhosis   0.0       NCI-H292 none   13.7       NCI-H292 IL-4   0.0       NCI-H292 IL-9   17.4       NCI-H292 IL-13   20.7       NCI-H292 IFN gamma   13.0       HPAEC none   0.0       HPAEC TNF alpha + IL-1 beta   0.0       Lung fibroblast none   0.0       Lung fibroblast TNF alpha + IL-1 beta   0.0       Lung fibroblast IL-4   0.0       Lung fibroblast IL-9   0.0       Lung fibroblast IL-13   0.0       Lung fibroblast IFN gamma   0.0       Dermal fibroblast CCD1070 rest   4.2       Dermal fibroblast CCD1070 TNF alpha   0.0       Dermal fibroblast CCD1070 IL-1 beta   1.0       Dermal fibroblast IFN gamma   100.0       Dermal fibroblast IL-4   78.5       Dermal Fibroblasts rest   59.9       Neutrophils TNFa + LPS   0.0       Neutrophils rest   0.0       Colon   0.0       Lung   0.0       Thymus   0.0       Kidney   0.0                    
     [0754]               TABLE NI                          Panel 4D                             Rel. Exp. (%)   Rel. Exp. (%)           Ag241, Run   Ag3074, Run       Tissue Name   165010380   162598884                                 Secondary Th1 act   5.6   0.0       Secondary Th2 act   1.7   0.0       Secondary Tr1 act   0.0   0.0       Secondary Th1 rest   0.0   0.0       Secondary Th2 rest   0.0   0.0       Secondary Tr1 rest   0.0   0.0       Primary Th1 act   40.9   33.7       Primary Th2 act   2.0   0.0       Primary Tr1 act   6.7   0.0       Primary Th1 rest   1.5   0.0       Primary Th2 rest   0.0   0.0       Primary Tr1 rest   0.0   0.0       CD45RA CD4 lymphocyte act   2.7   0.0       CD45RO CD4 lymphocyte act   5.7   0.0       CD8 lymphocyte act   0.0   2.6       Secondary CD8 lymphocyte rest   1.6   11.2       Secondary CD8 lymphocyte act   0.0   0.0       CD4 lymphocyte none   0.0   0.0       2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0   0.0       LAK cells rest   0.0   0.0       LAK cells IL-2   1.7   0.0       LAK cells IL-2 + IL-12   1.7   0.0       LAK cells IL-2 + IFN gamma   0.0   0.0       LAK cells IL-2 + IL-18   0.0   1.6       LAK cells PMA/ionomycin   0.2   0.0       NK Cells IL-2 rest   0.0   0.0       Two Way MLR 3 day   0.0   0.0       Two Way MLR 5 day   0.0   0.0       Two Way MLR 7 day   0.0   0.0       PBMC rest   0.0   0.0       PBMC PWM   14.5   2.2       PBMC PHA-L   4.1   2.0       Ramos (B cell) none   0.0   0.0       Ramos (B cell) ionomycin   0.0   0.0       B lymphocytes PWM   27.2   4.2       B lymphocytes CD40L and IL-4   3.1   0.0       EOL-1 dbcAMP   0.0   0.0       EOL-1 dbcAMP PMA/ionomycin   0.0   0.0       Dendritic cells none   0.0   0.0       Dendritic cells LPS   0.0   2.8       Dendritic cells anti-CD40   0.0   0.0       Monocytes rest   0.0   0.0       Monocytes LPS   1.6   0.0       Macrophages rest   0.0   0.0       Macrophages LPS   0.0   0.0       HUVEC none   0.0   0.0       HUVEC starved   0.0   0.0       HUVEC IL-1beta   0.0   0.0       HUVEC IFN gamma   0.0   0.0       HUVEC TNF alpha + IFN gamma   0.0   0.0       HUVEC TNF alpha + IL4   0.0   0.0       HUVEC IL-11   0.0   0.0       Lung Microvascular EC none   0.0   0.0       Lung Microvascular EC   0.0   0.0       TNFalpha + IL-1beta       Microvascular Dermal EC none   0.0   0.0       Microsvasular Dermal EC   0.0   0.0       TNFalpha + IL-1beta       Bronchial epithelium   1.4   0.0       TNFalpha + IL1beta       Small airway epithelium none   0.0   0.0       Small airway epithelium   0.0   0.0       TNFalpha + IL-1beta       Coronery artery SMC rest   6.9   0.0       Coronery artery SMC   0.0   0.0       TNFalpha + IL-1beta       Astrocytes rest   0.0   0.0       Astrocytes   1.3   12.9       TNFalpha + IL-1beta       KU-812 (Basophil) rest   0.0   0.0       KU-812 (Basophil) PMA/ionomycin   0.0   0.0       CCD1106 (Keratinocytes) none   0.0   0.0       CCD1106 (Keratinocytes)   0.0   0.0       TNFalpha + IL-1beta       Liver cirrhosis   10.2   2.7       Lupus kidney   0.2   3.1       NCI-H292 none   19.6   9.9       NCI-H292 IL-4   25.3   3.5       NCI-H292 IL-9   74.7   31.6       NCI-H292 IL-13   21.0   12.8       NCI-H292 IFN gamma   23.2   29.1       HPAEC none   0.0   0.0       HPAEC TNF alpha + IL-1 beta   0.0   0.0       Lung fibroblast none   0.0   0.0       Lung fibroblast   0.0   0.0       TNF alpha + IL-1 beta       Lung fibroblast IL-4   0.0   0.0       Lung fibroblast IL-9   0.0   0.0       Lung fibroblast IL-13   0.0   2.6       Lung fibroblast IFN gamma   0.0   0.0       Dermal fibroblast CCD1070 rest   5.5   3.2       Dermal fibroblast CCD1070   1.6   0.0       TNF alpha       Dermal fibroblast CCD1070   2.6   0.0       IL-1 beta       Dermal fibroblast IFN gamma   100.0   100.0       Dermal fibroblast IL-4   87.7   61.1       IBD Colitis 2   0.0   0.0       IBD Crohn&#39;s   0.0   0.0       Colon   52.5   3.0       Lung   43.5   25.3       Thymus   9.7   3.7       Kidney   4.7   4.9                    
     [0755] AI.05 chondrosarcoma Summary: Ag3074 Highest expression of this gene is detected in IL-1b/oncostatin treated chondrosarcoma cell line (SW1353). Interestingly, expression of this gene appears to be somewhat up-regulated upon IL-1 treatment, a potent activator of pro-inflammatory cytokines and matrix metalloproteinases, which participate in the destruction of cartilage observed in Osteoarthritis (OA). Modulation of the expression of this transcript in chondrocytes by either small molecules or antisense might be important for preventing the degeneration of cartilage observed in OA and Rheumatoid Arthritis.  
     [0756] AI_comprehensive panel_v1.0 Summary: Ag3074 Low but significant levels of expression of this gene are detected in in joint tissue from osteoarthritic (OA) patients including OA bone and adjacent bone as well as OA cartilage, OA synovium and OA synovial fluid samples. This gene is not expressed at significant levels in corresponding normal tissues. This gene codes for tandem acid-sensitive potassium channel TASK5. This family of K+ channels are very sensitive to small changes in extracellular pH, suggesting that TASK has a role in cellular responses to changes in extracellular pH (OMIM 603220). Therefore, small molecule therapeutics and antibody therapeutics based on the protein encoded for by this gene could reduce or inhibit inflammation and tissue destruction associated with the onset and progression of osteoarthritis and rheumatoid arthritis.  
     [0757] Low level expression of this gene is also detected in samples derived from normal lung samples, COPD lung, emphysema, atopic asthma, asthma, allergy, Crohn&#39;s disease (normal matched control and diseased), ulcerative colitis(normal matched control and diseased), and psoriasis (normal matched control and diseased). Therefore, therapeutic modulation of this gene product may ameliorate symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, and inflammatory bowel disease.  
     [0758] Panel 1.3D Summary: Ag241/Ag3074 Three experiments with two different probe and primer sets produce results that are in very good agreement. Expression of this gene in this panel is most prominent in cancer cell lines, with highest expression in a gastric cancer cell line (CTs=28). Significant levels of expression are also seen in cell lines derived from prostate cancer, ovarian cancer, breast cancer, lung cancer, and renal cancer. Thus, the therapeutic inhibition of this gene activity, through the use of small molecule drugs or antibodies, might be of utility in the treatment of the above listed cancer types. In addition, expression of this gene could be used as a diagnostic marker for cancer.  
     [0759] Among metabolic tissues, this gene has a low level of expression in adrenal, pituitary, heart and adipose. Thus, this gene product may be a small molecule target for the treatment of metabolic and endocrine disease, including the adrenalopathies, obesity and Type 2 diabetes.  
     [0760] Results from one experiment with the Ag241 (Run 165628181) show low/undetectable levels of expression in all the samples on this panel (CTs&gt;35).  
     [0761] See Maingret F, Patel A J, Lesage F, Lazdunski M, Honore E. Lysophospholipids open the two-pore domain mechano-gated K(+) channels TREK-1 and TRAAK. J Biol Chem. Apr. 7, 2000;275(14):10128-33. PMID: 10744694; and Ouadid-Ahidouch H, Chaussade F, Roudbaraki M, Slomianny C, Dewailly E, Delcourt P, Prevarskaya N. KV1.1 K(+) channels identification in human breast carcinoma cells: involvement in cell proliferation. Biochem Biophys Res Commun November 2000 19;278(2):272-7. (the report from Ouadid-Ahidouch et al. shows how potassium current are important for breast cancer cell proliferation, suggesting that CG54092-01, a potassium channel, plays a role in tumor cell growth and proliferation).  
     [0762] Panel 2D Summary: Ag241/Ag3041 The expression of the this gene gene was assessed in three independent runs with good concordance between the runs. This gene is expressed at a higher level in colon, thyroid, breast and bladder cancer samples compared to normal adjacent tissues. In addition, significant levels of expression are seen in ovarian cancer samples. This expression is in agreement with the cell-line expression seen in Panels 1.3D and 3D. Hence this gene can be used as a diagnostic marker for these cancers. Furthermore, targeting of TASK5 encoded by this gene with a human monoclonal antibody that results in an inhibition of the activity of the associated channel will have therapeutic effect on tumors, preferably on breast, ovarian and colon cell carcinoma and will result in reduced cell growth and proliferation.  
     [0763] Panel 3D Summary: Ag241 The expression of this gene was assessed in one run. This gene is expressed in in several cell lines including melanoma, gastric cancer, kidney cancer, cervical cancer and lung cancer cell lines. Thus, the therapeutic inhibition of this gene activity, through the use of small molecule drugs or antibodies, might be useful in the treatment of the above listed cancer types.  
     [0764] Panel 4.1D Summary: Ag3074 Highest expression is seen in IFN-gamma treated dermal fibroblasts (CT33.3). Please see Panel 4D for discussion of this gene in autoimmune disease.  
     [0765] Panel 4D Summary: Ag241/Ag3074 Two experiments with two different probe and primer sets show highest expression of this gene in dermal fibroblasts treated with IFN-gamma (CTs=30-33). Significant expression is also seen in dermal fibroblasts treated with IL-4. This expression suggests that the protein encoded by this gene may be involved in skin disorders, such as psoriasis. Significant levels of expression are also seen in both treated and untreated samples derived from the mucoepidermoid pulmonary cell line NCI-H292, astrocytes and some activated T cell populations. This expression profile suggests that the gene product may also be involved in inflammatory processes that affect the lung. Therefore, therapeutic modulation of the expression or function of the protein encoded by this gene may be effective in the treatment of asthma, allergies, emphysema and COPD.  
     [0766] O. CG55798-02: Olfactory Receptor.  
     [0767] Expression of gene CG55798-02 was assessed using the primer-probe sets Ag1500, Ag2609 and Ag2611, described in Tables OA, OB and OC. Results of the RTQ-PCR runs are shown in Tables OD, OE, OF, OG, OH and OI. Please note that CG55798-02 represents a full length physical clone.  
               TABLE OA                          Probe Name Ag1500                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-tgattgtctgtgtggataaacg-3′   22   140   196               Probe   TET-5′-tcttcctcagccacctctctaccctg-3′-TAMRA   26   182   197               Reverse   5′-ttatggttgtgaccaggatctc-3′   22   208   198                  
 
     [0768]               TABLE OB                          Probe Name Ag2609                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-cattgtgattgtctgtgtggat-3′   22   135   199               Probe   TET-5′-tcttcctcagccacctctctaccctg-3′-TAMRA   26   182   200               Reverse   5′-ttatggttgtgaccaggatctc-3′   22   208   201                    
     [0769]               TABLE OG                          Probe Name Ag2611                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-tgattgtctgtgtggataaacg-3′   22   140   202               Probe   TET-5′-tcttcctcagccacctctctaccctg-3′-TAMRA   26   182   203               Reverse   5′-ttatggttgtgaccaggatctc-3′   122   208   204                    
     [0770]               TABLE OD                          CNS_neurodegeneration_v1.0                             Rel. Exp. (%)   Rel. Exp. (%)           Ag2609, Run   Ag2611, Run       Tissue Name   208971592   208971593                                 AD 1 Hippo   12.7   2.2       AD 2 Hippo   39.5   11.1       AD 3 Hippo   7.3   0.9       AD 4 Hippo   4.2   0.8       AD 5 Hippo   36.3   14.0       AD 6 Hippo   63.7   11.3       Control 2 Hippo   11.3   3.5       Control 4 Hippo   2.5   0.9       Control (Path) 3 Hippo   5.0   1.1       AD 1 Temporal Ctx   21.3   7.5       AD 2 Temporal Ctx   31.2   12.1       AD 3 Temporal Ctx   9.5   1.9       AD 4 Temporal Ctx   28.1   3.7       AD 5 Inf Temporal Ctx   74.7   13.6       AD 5 Sup Temporal Ctx   18.2   4.2       AD 6 Inf Temporal Ctx   54.7   16.2       AD 6 Sup Temporal Ctx   39.8   13.6       Control 1 Temporal Ctx   3.2   1.0       Control 2 Temporal Ctx   7.1   3.1       Control 3 Temporal Ctx   8.2   2.6       Control 3 Temporal Ctx   6.3   5.1       Control (Path) 1 Temporal Ctx   34.6   9.7       Control (Path) 2 Temporal Ctx   19.6   5.1       Control (Path) 3 Temporal Ctx   0.0   0.8       Control (Path) 4 Temporal Ctx   12.7   2.5       AD 1 Occipital Ctx   12.8   100.0       AD 2 Occipital Ctx (Missing)   0.0   0.0       AD 3 Occipital Ctx   6.2   1.8       AD 4 Occipital Ctx   9.7   3.9       AD 5 Occipital Ctx   13.4   4.7       AD 6 Occipital Ctx   19.9   4.0       Control 1 Occipital Ctx   15.9   2.0       Control 2 Occipital Ctx   24.7   7.0       Control 3 Occipital Ctx   8.8   4.5       Control 4 Occipital Ctx   4.5   2.9       Control (Path) 1 Occipital Ctx   100.0   17.8       Control (Path) 2 Occipital Ctx   17.9   5.8       Control (Path) 3 Occipital Ctx   2.8   1.8       Control (Path) 4 Occipital Ctx   12.3   6.7       Control 1 Parietal Ctx   20.4   8.1       Control 2 Parietal Ctx   19.3   4.8       Control 3 Parietal Ctx   30.4   6.8       Control (Path) 1 Parietal Ctx   40.9   11.5       Control (Path) 2 Parietal Ctx   21.2   6.3       Control (Path) 3 Parietal Ctx   3.7   0.7       Control (Path) 4 Parietal Ctx   32.1   8.5                    
     [0771]               TABLE OE                          Panel 1.2                                 Rel.               Exp. (%)               Ag1500,               Run           Tissue Name   141889923                                         Endothelial cells   3.1           Heart (Fetal)   2.7           Pancreas   0.0           Pancreatic ca. CAPAN 2   2.8           Adrenal Gland   8.4           Thyroid   0.0           Salivary gland   39.8           Pituitary gland   1.4           Brain (fetal)   1.2           Brain (whole)   5.0           Brain (amygdala)   4.3           Brain (cerebellum)   13.7           Brain (hippocampus)   31.4           Brain (thalamus)   50.7           Cerebral Cortex   100.0           Spinal cord   18.3           glio/astro U87-MG   12.1           glio/astro U-118-MG   0.0           astrocytoma SW1783   11.6           neuro*; met SK-N-AS   8.5           astrocytoma SF-539   1.1           astrocytoma SNB-75   22.4           glioma SNB-19   19.1           glioma U251   2.4           glioma SF-295   12.2           Heart   15.5           Skeletal Muscle   7.0           Bone marrow   1.7           Thymus   0.9           Spleen   0.0           Lymph node   0.0           Colorectal Tissue   6.2           Stomach   0.0           Small intestine   2.4           Colon ca. SW480   1.1           Colon ca.* SW620 (SW480 met)   5.8           Colon ca. HT29   14.2           Colon ca. HCT-116   3.2           Colon ca. CaCo-2   10.8           Colon ca. Tissue (ODO3866)   17.8           Colon ca. HCC-2998   6.9           Gastric ca.* (liver met) NCI-N87   12.2           Bladder   17.4           Trachea   0.0           Kidney   14.9           Kidney (fetal)   16.7           Renal ca. 786-0   8.0           Renal ca. A498   11.5           Renal ca. RXF 393   3.6           Renal ca. ACHN   4.2           Renal ca. UO-31   8.0           Renal ca. TK-10   24.5           Liver   0.0           Liver (fetal)   1.1           Liver ca. (hepatoblast) HepG2   1.9           Lung   0.0           Lung (fetal)   1.0           Lung ca. (small cell) LX-1   30.4           Lung ca. (small cell) NCI-H69   65.5           Lung ca. (s. cell var.) SHP-77   1.5           Lung ca. (large cell)NCI-H460   23.2           Lung ca. (non-sm. cell) A549   13.9           Lung ca. (non-s. cell) NCI-H23   31.4           Lung ca. (non-s. cell) HOP-62   28.5           Lung ca. (non-s. cl) NCI-H522   51.1           Lung ca. (squam.) SW 900   4.3           Lung ca. (squam.) NCI-H596   22.4           Mammary gland   18.2           Breast ca.* (pl. ef) MCF-7   4.5           Breast ca.* (pl. ef) MDA-MB-231   0.0           Breast ca.* (pl. ef) T47D   91.4           Breast ca. BT-549   10.6           Breast ca. MDA-N   63.3           Ovary   7.9           Ovarian ca. OVCAR-3   8.1           Ovarian ca. OVCAR-4   20.2           Ovarian ca. OVCAR-5   95.9           Ovarian ca. OVCAR-8   88.3           Ovarian ca. IGROV-1   24.7           Ovarian ca. (ascites) SK-OV-3   16.4           Uterus   1.1           Placenta   27.7           Prostate   3.2           Prostate ca.* (bone met) PC-3   14.5           Testis   0.0           Melanoma Hs688(A).T   2.3           Melanoma* (met) Hs688(B).T   12.3           Melanoma UACC-62   54.7           Melanoma M14   89.5           Melanoma LOX IMVI   0.0           Melanoma* (met) SK-MEL-5   21.5                        
     [0772]               TABLE OF                          Panel 1.3D                             Rel. Exp. (%)   Rel. Exp. (%)           Ag2609, Run   Ag2611, Run       Tissue Name   166219826   166190369                                 Liver adenocarcinoma   0.0   0.0       Pancreas   0.0   0.0       Pancreatic ca. CAPAN2   0.0   7.0       Adrenal gland   12.9   0.0       Thyroid   0.0   0.0       Salivary gland   6.2   0.0       Pituitary gland   0.0   0.0       Brain (fetal)   26.4   0.0       Brain (whole)   26.2   26.8       Brain (amygdala)   3.9   5.4       Brain (cerebellum)   0.0   6.6       Brain (hippocampus)   17.2   6.2       Brain (substantia nigra)   31.9   78.5       Brain (thalamus)   82.4   100.0       Cerebral Cortex   0.0   19.2       Spinal cord   100.0   100.0       glio/astro U87-MG   0.0   0.0       glio/astro U-118-MG   0.0   0.0       astrocytoma SW1783   6.9   0.0       neuro*; met SK-N-AS   0.0   0.0       astrocytoma SF-539   0.0   0.0       astrocytoma SNB-75   0.0   0.0       glioma SNB-19   5.7   5.7       glioma U251   0.0   0.0       glioma SF-295   6.7   0.0       Heart (fetal)   0.0   6.1       Heart   0.0   0.0       Skeletal muscle (fetal)   0.0   0.0       Skeletal muscle   0.0   0.0       Bone marrow   0.0   0.0       Thymus   0.0   0.0       Spleen   0.0   0.0       Lymph node   0.0   0.0       Colorectal   6.7   0.0       Stomach   0.0   0.0       Small intestine   0.0   15.4       Colon ca. SW480   0.0   0.0       Colon ca.* SW620(SW480 met)   0.0   0.0       Colon ca. HT29   0.0   0.0       Colon ca. HCT-116   0.0   0.0       Colon ca. CaCo-2   0.0   0.0       Colon ca. tissue(ODO3866)   0.0   0.0       Colon ca. HCC-2998   0.0   0.0       Gastric ca.* (liver met) NCI-N87   0.0   0.0       Bladder   0.0   0.0       Trachea   0.0   0.0       Kidney   0.0   0.0       Kidney (fetal)   0.0   0.0       Renal ca. 786-0   0.0   0.0       Renal ca. A498   0.0   0.0       Renal ca. RXF 393   12.7   16.5       Renal ca. ACHN   0.0   0.0       Renal ca. UO-31   0.0   0.0       Renal ca. TK-10   7.4   0.0       Liver   0.0   0.0       Liver (fetal)   0.0   0.0       Liver ca. (hepatoblast) HepG2   0.0   8.0       Lung   0.0   0.0       Lung (fetal)   0.0   0.0       Lung ca. (small cell) LX-1   19.3   2.6       Lung ca. (small cell) NCI-H69   0.0   0.0       Lung ca. (s. cell var.) SHP-77   0.0   0.0       Lung ca. (large cell)NCI-H460   0.0   0.0       Lung ca. (non-sm. cell) A549   0.0   0.0       Lung ca. (non-s. cell) NCI-H23   10.2   0.0       Lung ca. (non-s. cell) HOP-62   0.0   6.2       Lung ca. (non-s. cl) NCI-H522   0.0   0.0       Lung ca. (squam.) SW 900   0.0   0.0       Lung ca. (squam.) NCI-H596   0.0   0.0       Mammary gland   0.0   0.0       Breast ca.* (pl. ef) MCF-7   0.0   0.0       Breast ca.* (pl. ef) MDA-MB-231   0.0   0.0       Breast ca.* (pl. ef) T47D   22.1   32.5       Breast ca. BT-549   0.0   0.0       Breast ca. MDA-N   3.2   29.7       Ovary   0.0   0.0       Ovarian ca. OVCAR-3   0.0   0.0       Ovarian ca. OVCAR-4   0.0   0.0       Ovarian ca. OVCAR-5   10.7   0.0       Ovarian ca. OVCAR-8   6.0   32.8       Ovarian ca. IGROV-1   0.0   0.0       Ovarian ca.* (ascites) SK-OV-3   8.8   0.0       Uterus   0.0   0.0       Placenta   38.7   27.9       Prostate   0.0   0.0       Prostate ca.* (bone met)PC-3   0.0   6.5       Testis   34.9   14.9       Melanoma Hs688(A).T   0.0   0.0       Melanoma* (met) Hs688(B).T   0.0   0.0       Melanoma UACC-62   0.0   32.8       Melanoma M14   0.0   18.4       Melanoma LOX IMVI   0.0   0.0       Melanoma* (met) SK-MEL-5   7.9   0.0       Adipose   0.0   0.0                    
     [0773]               TABLE OG                          Panel 2.2                             Rel. Exp. (%)   Rel. Exp. (%)           Ag2609, Run   Ag2611, Run       Tissue Name   175128270   175128271                                 Normal Colon   6.3   0.0       Colon cancer (OD06064)   0.0   0.0       Colon Margin (OD06064)   0.0   0.0       Colon cancer (OD06159)   0.0   0.0       Colon Margin (OD06159)   5.4   0.0       Colon cancer (OD06297-04)   0.0   0.0       Colon Margin (OD06297-05)   6.0   0.0       CC Gr.2 ascend colon   0.0   0.0       (ODO3921)       CC Margin (ODO3921)   0.0   0.0       Colon cancer   0.0   0.0       metastasis (OD06104)       Lung Margin (OD06104)   0.0   0.0       Colon mets to lung   0.0   0.0       (OD04451-01)       Lung Margin (OD04451-02)   0.0   0.0       Normal Prostate   0.0   0.0       Prostate Cancer (OD04410)   0.0   0.0       Prostate Margin (OD04410)   0.0   0.0       Normal Ovary   0.0   0.0       Ovarian cancer (OD06283-03)   0.0   0.0       Ovarian Margin (OD06283-07)   7.1   11.0       Ovarian Cancer 064008   28.7   0.0       Ovarian cancer (OD06145)   0.0   5.6       Ovarian Margin (OD06145)   15.9   0.0       Ovarian cancer (OD06455-03)   6.8   0.0       Ovarian Margin (OD06455-07)   0.0   0.0       Normal Lung   0.0   0.0       Invasive poor diff.   0.0   0.0       lung adeno (ODO4945-01       Lung Margin (ODO4945-03)   3.1   0.0       Lung Malignant   0.0   0.0       Cancer (OD03126)       Lung Margin (OD03126)   0.0   0.0       Lung Cancer (OD05014A)   0.0   0.0       Lung Margin (OD05014B)   0.0   4.3       Lung cancer (OD06081)   0.0   0.0       Lung Margin (OD06081)   0.0   8.0       Lung Cancer (OD04237-01)   0.0   0.0       Lung Margin (OD04237-02)   0.0   0.0       Ocular Melanoma Metastasis   0.0   10.3       Ocular Melanoma   0.0   0.0       Margin (Liver)       Melanoma Metastasis   16.5   15.2       Melanoma Margin (Lung)   0.0   0.0       Normal Kidney   7.4   11.0       Kidney Ca, Nuclear   4.3   0.0       grade 2 (OD04338)       Kidney Margin (OD04338)   0.0   2.8       Kidney Ca Nuclear   5.6   10.1       grade 1/2 (OD04339)       Kidney Margin (OD04339)   0.0   7.0       Kidney Ca, Clear cell   0.0   7.3       type (OD04340)       Kidney Margin (OD04340)   0.0   0.0       Kidney Ca, Nuclear   0.0   0.0       grade 3 (OD04348)       Kidney Margin (OD04348)   14.6   12.7       Kidney malignant   9.7   9.7       cancer (OD06204B)       Kidney normal adjacent   0.0   0.0       tissue (OD06204E)       Kidney Cancer (OD04450-01)   18.0   0.0       Kidney Margin (OD04450-03)   0.0   0.0       Kidney Cancer 8120613   0.0   0.0       Kidney Margin 8120614   0.0   0.0       Kidney Cancer 9010320   0.0   0.0       Kidney Margin 9010321   0.0   0.0       Kidney Cancer 8120607   0.0   0.0       Kidney Margin 8120608   0.0   0.0       Normal Uterus   9.8   14.5       Uterine Cancer 064011   0.0   0.0       Normal Thyroid   0.0   0.0       Thyroid Cancer 064010   0.0   0.0       Thyroid Cancer A302152   0.0   15.1       Thyroid Margin A302153   0.0   0.0       Normal Breast   18.7   33.9       Breast Cancer (OD04566)   0.0   0.0       Breast Cancer 1024   21.2   17.7       Breast Cancer (OD04590-01)   0.0   0.0       Breast Cancer Mets   8.4   0.0       (OD04590-03)       Breast Cancer Metastasis   0.0   0.0       (OD04655-05)       Breast Cancer 064006   1.5   9.9       Breast Cancer 9100266   100.0   100.0       Breast Margin 9100265   5.9   7.8       Breast Cancer A209073   3.7   7.0       Breast Margin A2090734   0.0   27.5       Breast cancer (OD06083)   9.9   14.3       Breast cancer node   13.5   5.3       metastasis (OD06083)       Normal Liver   0.0   0.0       Liver Cancer 1026   0.0   0.0       Liver Cancer 1025   0.0   0.0       Liver Cancer 6004-T   0.0   0.0       Liver Tissue 6004-N   0.0   0.0       Liver Cancer 6005-T   5.2   0.0       Liver Tissue 6005-N   0.0   0.0       Liver Cancer 064003   0.0   0.0       Normal Bladder   0.0   0.0       Bladder Cancer 1023   0.0   9.0       Bladder Cancer A302173   10.2   0.0       Normal Stomach   12.3   0.0       Gastric Cancer 9060397   0.0   0.0       Stomach Margin 9060396   0.0   0.0       Gastric Cancer 9060395   11.4   0.0       Stomach Margin 9060394   0.0   0.0       Gastric Cancer 064005   0.0   0.0                    
     [0774]               TABLE OH                          Panel 4D                                 Rel. Exp. (%)   Rel. Exp. (%)   Rel. Exp. (%)           Ag2609, Run   Ag2609, Run   Ag2611, Run       Tissue Name   164289991   164347907   164398661                                     Secondary Th1 act   6.4   6.4   4.8       Secondary Th2 act   12.7   12.7   13.9       Secondary Tr1 act   0.9   0.9   14.7       Secondary Th1 rest   3.9   3.9   0.0       Secondary Th2 rest   0.0   0.0   0.0       Secondary Tr1 rest   0.4   0.4   0.0       Primary Th1 act   0.0   0.0   19.6       Primary Th2 act   9.2   9.2   0.0       Primary Tr1 act   4.2   4.2   7.1       Primary Th1 rest   16.8   16.8   20.4       Primary Th2 rest   13.6   13.6   15.0       Primary Tr1 rest   1.5   1.5   0.0       CD45RA CD4   0.0   0.0   13.5       lymphocyte act       CD45RO CD4   0.2   0.2   1.3       lymphocyte act       CD8 lymphocyte act   0.0   0.0   4.5       Secondary CD8   13.5   13.5   4.5       lymphocyte rest       Secondary CD8   13.5   13.5   7.3       lymphocyte act       CD4 lymphocyte none   10.2   10.2   10.5       2ry Th1/Th2/Tr1 —     16.3   16.3   5.7       anti-CD95 CH11       LAK cells rest   17.1   17.1   6.3       LAK cells IL-2   0.0   0.0   0.0       LAK cells   3.0   3.0   19.5       IL-2 + IL-12       LAK cells IL-2 + IFN   7.7   7.7   0.0       gamma       LAK cells IL-2 +   4.1   4.1   0.0       IL-18       LAK cells   2.0   2.0   14.2       PMA/ionomycin       NK Cells IL-2 rest   18.3   18.3   0.0       Two Way MLR 3 day   15.6   15.6   15.0       Two Way MLR 5 day   15.8   15.8   0.0       Two Way MLR 7 day   0.0   0.0   8.1       PBMC rest   1.6   1.6   0.0       PBMC PWM   10.2   10.2   14.2       PBMC PHA-L   6.7   6.7   20.9       Ramos (B cell) none   17.1   17.1   7.8       Ramos (B cell)   8.2   8.2   0.0       ionomycin       B lymphocytes PWM   3.7   3.7   4.5       B lymphocytes   7.2   7.2   13.2       CD40L and IL-4       EOL-1 dbcAMP   9.4   9.4   2.1       EOL-1 dbcAMP   25.0   25.0   0.0       PMA/ionomycin       Dendritic cells none   43.2   43.2   27.2       Dendritic cells LPS   17.6   17.6   11.3       Dendritic cells   24.1   24.1   5.6       anti-CD40       Monocytes rest   2.2   2.2   0.0       Monocytes LPS   69.3   69.3   100.0       Macrophages rest   100.0   100.0   97.3       Macrophages LPS   14.9   14.9   8.1       HUVEC none   0.0   0.0   0.0       HUVEC starved   4.7   4.7   19.1       HUVEC IL-1beta   0.0   0.0   0.0       HUVEC IFN gamma   4.9   4.9   0.0       HUVEC TNF alpha +   15.3   15.3   6.9       IFN gamma       HUVEC TNF   18.4   18.4   0.0       alpha + IL4       HUVEC IL-11   0.8   0.8   6.0       Lung Microvascular   6.5   6.5   66.0       EC none       Lung Microvascular   9.5   9.5   18.3       EC TNFalpha +       IL-1beta       Microvascular   0.4   0.4   0.0       Dermal EC none       Microsvasular Dermal   16.2   16.2   3.0       EC TNFalpha +       IL-1beta       Bronchial epithelium   1.3   1.3   6.3       TNFalpha +       IL1beta       Small airway   2.9   2.9   0.0       epithelium none       Small airway   10.9   10.9   3.9       epithelium       TNFalpha +       IL-1beta       Coronery artery   0.0   0.0   0.0       SMC rest       Coronery artery SMC   0.4   0.4   5.9       TNFalpha +       IL-1beta       Astrocytes rest   9.9   9.9   0.0       Astrocytes   0.0   0.0   0.0       TNFalpha +       IL-1beta       KU-812 (Basophil)   3.1   3.1   4.0       rest       KU-812 (Basophil)   3.9   3.9   4.8       PMA/ionomycin       CCD1106   9.6   9.6   0.0       (Keratinocytes) none       CCD1106   6.5   6.5   0.0       (Keratinocytes)       TNFalpha +       IL-1beta       Liver cirrhosis   22.5   22.5   25.9       Lupus kidney   3.0   3.0   0.0       NCI-H292 none   4.4   4.4   0.0       NCI-H292 IL-4   3.5   3.5   0.0       NCI-H292 IL-9   1.5   1.5   0.0       NCI-H292 IL-13   9.5   9.5   0.0       NCI-H292 IFN gamma   0.0   0.0   0.0       HPAEC none   0.0   0.0   0.0       HPAEC TNF alpha +   3.2   3.2   0.0       IL-1 beta       Lung fibroblast none   4.1   4.1   0.0       Lung fibroblast   0.0   0.0   0.0       TNF alpha +       IL-1 beta       Lung fibroblast IL-4   5.7   5.7   0.0       Lung fibroblast IL-9   0.0   0.0   0.0       Lung fibroblast IL-13   0.0   0.0   0.0       Lung/fibroblast IFN   0.0   0.0   0.0       gamma       Dermal fibroblast   5.0   5.0   13.6       CCD1070 rest       Dermal fibroblast   14.7   14.7   36.1       CCD1070 TNF alpha       Dermal fibroblast   0.0   0.0   6.3       CCD1070 IL-1 beta       Dermal fibroblast   0.0   0.0   0.0       IFN gamma       Dermal   0.0   0.0   6.3       fibroblast IL-4       IBD Colitis 2   9.3   9.3   0.0       IBD Crohn&#39;s   0.0   0.0   0.0       Colon   1.0   1.0   6.8       Lung   11.7   11.7   19.8       Thymus   19.3   19.3   20.2       Kidney   4.4   4.4   20.2                    
     [0775]               TABLE OI                          Panel CNS_1                                 Rel.Exp. (%)               Ag2609, Run           Tissue Name   171664238                                         BA4 Control   0.0           BA4 Control2   6.5           BA4 Alzheimer&#39;s2   6.6           BA4 Parkinson&#39;s   7.2           BA4 Parkinson&#39;s2   0.0           BA4 Huntington&#39;s   14.7           BA4 Huntington&#39;s2   0.0           BA4 PSP   6.0           BA4 PSP2   8.5           BA4 Depression   12.2           BA4 Depression2   5.1           BA7 Control   18.6           BA7 Control2   0.0           BA7 Alzheimer&#39;s2   5.6           BA7 Parkinson&#39;s   3.7           BA7 Parkinson&#39;s2   0.0           BA7 Huntington&#39;s   8.8           BA7 Huntington&#39;s2   9.5           BA7 PSP   15.0           BA7 PSP2   0.0           BA7 Depression   9.1           BA9 Control   5.9           BA9 Control2   10.6           BA9 Alzheimer&#39;s   0.0           BA9 Alzheimer&#39;s2   0.0           BA9 Parkinson&#39;s   18.8           BA9 Parkinson&#39;s2   5.4           BA9 Huntington&#39;s   11.6           BA9 Huntington&#39;s2   0.0           BA9 PSP   3.3           BA9 PSP2   0.0           BA9 Depression   4.8           BA9 Depression2   0.0           BA17 Control   9.6           BA17 Control2   8.4           BA17 Alzheimer&#39;s2   0.0           BA17 Parkinson&#39;s   18.4           BA17 Parkinson&#39;s2   20.4           BA17 Huntington&#39;s   17.9           BA17 Huntington&#39;s2   0.0           BA17 Depression   12.2           BA17 Depression2   8.5           BA17 PSP   7.2           BA17 PSP2   0.0           Sub Nigra Control   49.3           Sub Nigra Control2   37.1           Sub Nigra Alzheimer&#39;s2   6.6           Sub Nigra Parkinson&#39;s2   19.1           Sub Nigra Huntington&#39;s   100.0           Sub Nigra Huntington&#39;s2   7.0           Sub Nigra PSP2   4.5           Sub Nigra Depression   0.0           Sub Nigra Depression2   4.8           Glob Palladus Control   9.5           Glob Palladus Control2   6.4           Glob Palladus Alzheimer&#39;s   4.8           Glob Palladus Alzheimer&#39;s2   13.6           Glob Palladus Parkinson&#39;s   38.2           Glob Palladus Parkinson&#39;s2   11.9           Glob Palladus PSP   0.0           Glob Palladus PSP2   0.0           Glob Palladus Depression   23.5           Temp Pole Control   0.0           Temp Pole Control2   0.0           Temp Pole Alzheimer&#39;s   0.0           Temp Pole Alzheimer&#39;s2   0.0           Temp Pole Parkinson&#39;s   0.0           Temp Pole Parkinson&#39;s2   3.2           Temp Pole Huntington&#39;s   0.0           Temp Pole PSP   0.0           Temp Pole PSP2   0.0           Temp Pole Depression2   0.0           Cing Gyr Control   17.9           Cing Gyr Control2   9.3           Cing Gyr Alzheimer&#39;s   11.9           Cing Gyr Alzheimer&#39;s2   0.0           Cing Gyr Parkinson&#39;s   38.4           Cing Gyr Parkinson&#39;s2   11.8           Cing Gyr Huntington&#39;s   29.1           Cing Gyr Huntington&#39;s2   25.5           Cing Gyr PSP   33.7           Cing Gyr PSP2   13.7           Cing Gyr Depression   17.8           Cing Gyr Depression2   19.8                        
     [0776] CNS_neurodegeneration_v1.0 Summary: Ag2611/Ag2609 This gene is expressed more highly in the temporal cortex of Alzheimer&#39;s diseased brain than in control brain without amyloid plaques, which are diagnostic and potentially causative of Alzheimer&#39;s disease. This gene encodes a protein with homology to GPCRs. GPCRs are readily targetable with drugs, and regulate many specific brain processes, including signaling processes, that are currently the target of FDA-approved pharmaceuticals that treat Alzheimer&#39;s disease, such as the cholinergic system. The major mechanisms proposed for AbetaP-induced cytotoxicity involve the loss of Ca2+ homeostasis and the generation of reactive oxygen species (ROS). The changes in Ca2+ homeostasis could be the result of changes in G-protein-driven releases of second messengers. Thus, targeting this class of molecule can have therapeutic potential in Alzheimer&#39;s disease treatment. In particular, the increased gene expression in brains affected by Alzheimer&#39;s indicates potential therapeutic value to drugs that target this GPCR.  
     [0777] See Kourie J I. Mechanisms of amyloid beta protein-induced modification in ion transport systems: implications for neurodegenerative diseases. Cell Mol Neurobiol June 2001;21(3):173-213  
     [0778] Panel 1.2 Summary: Ag1500 Highest expression of this gene is seen in the cerebral cortex (CT=30.4). Among tissues active in the central nervous system, this gene is also moderately expressed in the cerebellum, hippocampus, thalamus and spinal cord. Please see CNS_neurodegeneration_panel_v1.0 summary for description of the potential role of this gene in the treatment of CNS diseases.  
     [0779] Among tissues with metabolic function, this gene is expressed at low but significant levels in samples derived from the adrenal gland, heart and skeletal muscle. Therefore, the protein encoded by this gene may be important in the pathogenesis and/or treatment of disease in any or all of the above-named tissues.  
     [0780] This gene also shows an association with cancerous cell lines and is expressed in clusters of samples derived from breast, ovarian, melanoma and lung cancer cell lines. Thus, the expression of this gene could be used to distinguish samples derived from cell lines when compared to tissues. In addition, therapeutic modulation of this gene or its protein product, through the use of small molecule drugs or antibodies, might be beneficial in the treatment of ovarian cancer, breast cancer, lung cancer or melanoma.  
     [0781] Panel 1.3D Summary: Ag2611/Ag2609 Two experiments with two different probe/primer sets both show preferential expression of this gene in tissues originating in the central nervous system, with expression seen in the spinal cord (CT=33.1) and thalamus (CT=34.1). Please see CNS_neurodegeneration_panel_v1.0 summary for description of the potential role of this gene in the treatment of CNS diseases.  
     [0782] Panel 2.2 Summary: Ag2611/Ag2609 In two experiments using two different probe and primer sets, expression of this gene is limited to a sample derived from a breast cancer (CT=33.2) and appears to be overexpressed in breast cancer as compared to normal adjacent tissue. This suggests that this gene could be used to distinguish breast cancer samples from other samples and for the detection of breast cancer. Moreover, therapeutic inhibition of this gene, through the use of small molecule drugs or antibodies might be of use in the treatment of breast cancer.  
     [0783] Panel 4D Summary: Ag2611/Ag2609 This gene is expressed at moderate levels in LPS-activated monocytes but not in resting monocytes. Conversely, this gene is expressed at moderate levels in resting macrophages, but at low levels in activated macrophages. This pattern is evident in experiments using two different probe and primer sets that match this sequence. Since circulating monocytes and tissue macrophages are both developmentally related cell types, this gene could serve as a useful target for the development of small molecule drugs as well as therapeutic antibodies. Therapeutic antibodies and small molecule inhibitors that block the function of the protein encoded by this gene may be useful in reducing inflammation and autoimmune disease symptoms in patients with Crohn&#39;s disease, inflammatory bowel disease, asthma, psoriasis, and rheumatoid arthritis.  
     [0784] Panel CNS — 1 Summary: Ag2609 Expression of this gene is highest in the substantia nigra of a Huntington&#39;s disease patient, indicating that this gene may participate in the genetic dysregulation associated with the neurodegeneration that occurs in this brain region. The substantia nigra is also critical to the progression of Parkinson&#39;s disease neurodegeneration. Thus, pharmacological targeting of the GPCR encoded by this gene may help counter this genetic dysregulation and contribute to the restoration of normal function in Huntington&#39;s disease as well as potentially Parkinson&#39;s disease patients. Pharmacological modulation of GPCR signaling systems is the mechanism by which powerful depression therapies, such as SSRIs, exert their effect.  
     [0785] P. CG55838-02 and CG55838-03: Dual Specificity Mitogen-Activated Protein Kinase Kinase 2.  
     [0786] Expression of gene CG55838-02 and CG55838-03 was assessed using the primer-probe sets Ag2022 and Ag7706, described in Tables PA and PB. Results of the RTQ-PCR runs are shown in Tables PC, PD, PE, PF, PG and PH. Please note that primer probe Ag7706 is specific for CG55838-03. Also, please note that CG55838-03 represents a full-length physical clone.  
               TABLE PA                          Probe Name Ag2022                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-ccaggagtttgtcaataaatgc-3′   22   760   205               Probe   TET-5′-ctcatcaagaacccagcggagcg-3′-TAMRA   23   782   206               Reverse   5′-ttgatgaaggtgtggtttgtg-3′   21   823   207                  
 
     [0787]               TABLE PB                          Probe Name Ag7706                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-ctacatggctccacctcctaa-3′   21   709   208               Probe   TET-5′-ccccgacttccaggagtttgtca-3′-TAMRA   23   751   209               Reverse   5′-tgggttcttgatgaggcatt-3′   20   777   210                    
     [0788]               TABLE PC                          General_screening_panel_v1.7                                 Rel.Exp. (%)               Ag7706, Run           Tissue Name   318841791                                         Adipose   13.0           HUVEC   40.9           Melanoma* Hs688(A).T   0.0           Melanoma* Hs688(B).T   31.6           Melanoma (met) SK-MEL-5   25.3           Testis   8.9           Prostate ca. (bone met) PC-3   1.0           Prostate ca. DU145   22.7           Prostate pool   2.8           Uterus pool   0.6           Ovarian ca. OVCAR-3   10.6           Ovarian ca. (ascites) SK-OV-3   0.8           Ovarian ca. OVCAR-4   61.1           Ovarian ca. OVCAR-5   24.8           Ovarian ca. IGROV-1   100.0           Ovarian ca. OVCAR-8   46.7           Ovary   9.0           Breast ca. MCF-7   29.1           Breast ca. MDA-MB-231   62.4           Breast ca. BT-549   15.0           Breast ca. T47D   11.6           Breast pool   0.0           Trachea   10.7           Lung   10.9           Fetal Lung   12.1           Lung ca. NCI-N417   13.7           Lung ca. LX-1   5.9           Lung ca. NCI-H146   15.9           Lung ca. SHP-77   63.3           Lung ca. NCI-H23   71.2           Lung ca. NCI-H460   31.4           Lung ca. HOP-62   30.6           Lung ca. NCI-H522   41.8           Lung ca. DMS-114   6.9           Liver   2.6           Fetal Liver   10.2           Kidney pool   15.7           Fetal Kidney   12.8           Renal ca. 786-0   42.0           Renal ca. A498   9.3           Renal ca. ACHN   14.9           Renal ca. UO-31   14.3           Renal ca. TK-10   22.7           Bladder   6.8           Gastric ca. (liver met.) NCI-N87   0.5           Stomach   0.7           Colon ca. SW-948   11.8           Colon ca. SW480   2.7           Colon ca. (SW480 met) SW620   37.6           Colon ca. HT29   46.7           Colon ca. HCT-116   42.9           Colon cancer tissue   0.9           Colon ca. SW1116   8.2           Colon ca. Colo-205   5.6           Colon ca. SW-48   7.9           Colon   12.6           Small Intestine   2.0           Fetal Heart   15.3           Heart   2.0           Lymph Node pool 1   2.3           Lymph Node pool 2   20.6           Fetal Skeletal Muscle   16.8           Skeletal Muscle pool   3.3           Skeletal Muscle   43.2           Spleen   4.6           Thymus   4.9           CNS cancer (glio/astro) SF-268   19.6           CNS cancer (glio/astro) T98G   12.2           CNS cancer (neuro; met) SK-N-AS   1.2           CNS cancer (astro) SF-539   32.3           CNS cancer (astro) SNB-75   54.7           CNS cancer (glio) SNB-19   55.5           CNS cancer (glio) SF-295   12.2           Brain (Amygdala)   12.9           Brain (Cerebellum)   35.8           Brain (Fetal)   44.1           Brain (Hippocampus)   9.7           Cerebral Cortex pool   11.4           Brain (Substantia nigra)   6.5           Brain (Thalamus)   11.0           Brain (Whole)   30.8           Spinal Cord   5.0           Adrenal Gland   16.5           Pituitary Gland   8.5           Salivary Gland   6.3           Thyroid   10.5           Pancreatic ca. PANC-1   14.1           Pancreas pool   2.6                        
     [0789]               TABLE PD                          Panel 1.3D                             Rel. Exp. (%)   Rel. Exp. (%)           Ag2022, Run   Ag2022, Run       Tissue Name   165626371   165627116                                 Liver adenocarcinoma   23.2   15.8       Pancreas   9.6   4.3       Pancreatic ca. CAPAN2   4.1   4.4       Adrenal gland   8.0   10.3       Thyroid   12.1   9.6       Salivary gland   10.9   5.9       Pituitary gland   12.0   9.6       Brain (fetal)   13.6   7.6       Brain (whole)   47.3   25.0       Brain (amygdala)   33.7   19.9       Brain (cerebellum)   33.2   16.3       Brain (hippocampus)   42.6   21.6       Brain (Substantia nigra)   30.6   13.8       Brain (thalamus)   50.3   24.5       Cerebral Cortex   36.6   31.4       Spinal cord   16.8   8.7       glio/astro U87-MG   17.6   18.4       glio/astro U-118-MG   54.7   38.4       astrocytoma SW1783   13.5   12.8       neuro*; met SK-N-AS   15.4   12.9       astrocytoma SF-539   14.3   9.4       astrocytoma SNB-75   29.5   25.7       glioma SNB-19   23.7   17.8       glioma U251   38.4   34.4       glioma SF-295   18.4   17.2       Heart (fetal)   17.2   16.3       Heart   25.7   10.2       Skeletal muscle (fetal)   12.2   12.9       Skeletal muscle   100.0   100.0       Bone marrow   15.0   14.5       Thymus   7.6   8.1       Spleen   14.5   11.4       Lymph node   25.7   19.2       Colorectal   6.7   4.7       Stomach   14.5   10.0       Small intestine   30.1   32.3       Colon ca. SW480   9.2   6.7       Colon ca.* SW620(SW480 met)   3.1   4.1       Colon ca. HT29   1.4   2.5       Colon ca. HCT-116   8.5   9.1       Colon ca. CaCo-2   5.6   7.0       Colon ca. tissue(ODO3866)   11.8   11.5       Colon ca. HCC-2998   4.6   7.2       Gastric ca.* (liver met) NCI-N87   13.0   9.3       Bladder   3.4   4.2       Trachea   13.7   10.4       Kidney   14.6   6.3       Kidney (fetal)   9.2   4.2       Renal ca. 786-0   9.5   7.3       Renal ca. A498   23.2   19.3       Renal ca. RXF 393   16.8   15.9       Renal ca. ACHN   14.4   10.5       Renal ca. UO-31   11.2   8.1       Renal ca. TK-10   5.4   4.8       Liver   11.2   3.4       Liver (fetal)   24.1   18.7       Liver ca.   12.8   9.9       (hepatoblast) HepG2       Lung   11.4   11.8       Lung (fetal)   11.8   8.9       Lung ca. (small cell) LX-1   12.4   8.4       Lung ca. (small cell) NCI-H69   15.8   17.0       Lung ca. (s. cell var.) SHP-77   11.3   12.6       Lung ca. (large cell)NCI-H460   30.6   28.3       Lung ca. (non-sm. cell) A549   5.7   6.2       Lung ca. (non-s. cell) NCI-H23   6.3   7.0       Lung ca. (non-s. cell) HOP-62   13.1   12.0       Lung ca. (non-s. cl) NCI-H522   5.7   4.5       Lung ca. (squam.) SW 900   3.6   4.1       Lung ca. (squam.) NCI-H596   12.2   11.0       Mammary gland   7.2   8.8       Breast ca.* (pl. ef) MCF-7   9.6   9.1       Breast ca.* (pl. ef) MDA-MB-231   47.0   56.6       Breast ca.* (pl. ef) T47D   4.7   4.6       Breast ca. BT-549   19.6   20.6       Breast ca. MDA-N   6.3   6.2       Ovary   7.3   6.4       Ovarian ca. OVCAR-3   7.4   5.6       Ovarian ca. OVCAR-4   27.9   20.6       Ovarian ca. OVCAR-5   7.0   7.0       Ovarian ca. OVCAR-8   11.7   9.8       Ovarian ca. IGROV-1   3.5   2.3       Ovarian ca.* (ascites) SK-OV-3   23.7   17.0       Uterus   25.9   18.7       Placenta   10.9   6.3       Prostate   10.5   10.4       Prostate ca.* (bone met)PC-3   20.4   18.0       Testis   27.2   19.3       Melanoma Hs688(A).T   6.6   5.1       Melanoma* (met) Hs688(B).T   10.7   8.5       Melanoma UACC-62   43.5   36.1       Melanoma M14   42.0   36.9       Melanoma LOX IMVI   8.0   9.0       Melanoma* (met) SK-MEL-5   15.9   14.2       Adipose   4.8   3.8                    
     [0790]               TABLE PE                          Panel 2.2                                 Rel.Exp. (%)               Ag2022, Run           Tissue Name   174232815                                         Normal Colon   24.7           Colon cancer (OD06064)   14.4           Colon Margin (OD06064)   18.0           Colon cancer (OD06159)   12.2           Colon Margin (OD06159)   18.2           Colon cancer (OD06297-04)   15.5           Colon Margin (OD06297-05)   23.7           CC Gr.2 ascend colon (ODO3921)   25.7           CC Margin (ODO3921)   21.9           Colon cancer metastasis (OD06104)   6.0           Lung Margin (OD06104)   19.6           Colon mets to lung (OD04451-01)   30.1           Lung Margin (OD04451-02)   11.4           Normal Prostate   21.9           Prostate Cancer (OD04410)   9.1           Prostate Margin (OD04410)   11.2           Normal Ovary   58.2           Ovarian cancer (OD06283-03)   12.9           Ovarian Margin (OD06283-07)   8.5           Ovarian Cancer 064008   15.8           Ovarian cancer (OD06145)   19.2           Ovarian Margin (OD06145)   34.4           Ovarian cancer (OD06455-03)   11.0           Ovarian Margin (OD06455-07)   2.8           Normal Lung   11.3           Invasive poor diff. lung adeno (ODO4945-01   19.1           Lung Margin (ODO4945-03)   9.9           Lung Malignant Cancer (OD03126)   22.4           Lung Margin (OD03126)   8.6           Lung Cancer (OD05014A)   24.5           Lung Margin (OD05014B)   13.8           Lung cancer (OD06081)   12.4           Lung Margin (OD06081)   2.6           Lung Cancer (OD04237-01)   14.5           Lung Margin (OD04237-02)   29.7           Ocular Melanoma Metastasis   44.4           Ocular Melanoma Margin (Liver)   12.2           Melanoma Metastasis   32.5           Melanoma Margin (Lung)   13.2           Normal Kidney   14.9           Kidney Ca, Nuclear grade 2 (OD04338)   40.9           Kidney Margin (OD04338)   12.3           Kidney Ca Nuclear grade 1/2 (OD04339)   49.3           Kidney Margin (OD04339)   17.9           Kidney Ca, Clear cell type (OD04340)   21.0           Kidney Margin (OD04340)   18.0           Kidney Ca, Nuclear grade 3 (OD04348)   16.6           Kidney Margin (OD04348)   70.7           Kidney malignant cancer (OD06204B)   22.1           Kidney normal adjacent tissue (OD06204E)   18.7           Kidney Cancer (OD04450-01)   48.3           Kidney Margin (OD04450-03)   16.6           Kidney Cancer 8120613   14.1           Kidney Margin 8120614   40.6           Kidney Cancer 9010320   20.4           Kidney Margin 9010321   12.9           Kidney Cancer 8120607   48.0           Kidney Margin 8120608   37.9           Normal Uterus   11.9           Uterine Cancer 064011   16.7           Normal Thyroid   9.7           Thyroid Cancer 064010   19.1           Thyroid Cancer A302152   28.3           Thyroid Margin A302153   11.8           Normal Breast   12.3           Breast Cancer (OD04566)   12.9           Breast Cancer 1024   23.2           Breast Cancer (OD04590-01)   46.0           Breast Cancer Mets (OD04590-03)   35.6           Breast Cancer Metastasis (OD04655-05)   100.0           Breast Cancer 064006   19.3           Breast Cancer 9100266   8.3           Breast Margin 9100265   9.3           Breast Cancer A209073   3.6           Breast Margin A2090734   22.1           Breast cancer (OD06083)   47.3           Breast cancer node metastasis (OD06083)   49.0           Normal Liver   29.3           Liver Cancer 1026   31.2           Liver Cancer 1025   39.2           Liver Cancer 6004-T   36.1           Liver Tissue 6004-N   8.1           Liver Cancer 6005-T   74.2           Liver Tissue 6005-N   74.2           Liver Cancer 064003   45.7           Normal Bladder   19.3           Bladder Cancer 1023   29.9           Bladder Cancer A302173   31.0           Normal Stomach   48.6           Gastric Cancer 9060397   16.5           Stomach Margin 9060396   33.2           Gastric Cancer 9060395   14.6           Stomach Margin 9060394   34.4           Gastric Cancer 064005   25.3                        
     [0791]               TABLE PF                          Panel 4.1D                         Rel.Exp. (%)           Ag7706, Run       Tissue Name   311582896                             Secondary Th1 act   56.3       Secondary Th2 act   66.9       Secondary Tr1 act   14.3       Secondary Th1 rest   5.5       Secondary Th2 rest   14.9       Secondary Tr1 rest   15.2       Primary Th1 act   14.8       Primary Th2 act   41.2       Primary Tr1 act   45.7       Primary Th1 rest   4.8       Primary Th2 rest   14.8       Primary Tr1 rest   0.0       CD45RA CD4 lymphocyte act   43.2       CD45RO CD4 lymphocyte act   39.0       CD8 lymphocyte act   12.9       Secondary CD8 lymphocyte rest   4.5       Secondary CD8 lymphocyte act   9.7       CD4 lymphocyte none   5.2       2ry Th1/Th2/Tr1 anti-CD95 CH11   15.5       LAK cells rest   12.9       LAK cells IL-2   15.1       LAK cells IL-2 + IL-12   0.0       LAK cells IL-2 + IFN gamma   7.4       LAK cells IL-2 + IL-18   2.5       LAK cells PMA/ionomycin   12.0       NK Cells IL-2 rest   47.0       Two Way MLR 3 day   7.9       Two Way MLR 5 day   0.0       Two Way MLR 7 day   0.0       PBMC rest   0.0       PBMC PWM   11.0       PBMC PHA-L   2.8       Ramos (B cell) none   15.0       Ramos (B cell) ionomycin   61.1       B lymphocytes PWM   15.4       B lymphocytes CD40L and IL-4   50.0       EOL-1 dbcAMP   67.8       EOL-1 dbcAMP PMA/ionomycin   23.0       Dendritic cells none   67.8       Dendritic cells LPS   2.0       Dendritic cells anti-CD40   0.0       Monocytes rest   7.5       Monocytes LPS   22.2       Macrophages rest   4.1       Macrophages LPS   13.5       HUVEC none   48.0       HUVEC starved   49.7       HUVEC IL-1beta   54.3       HUVEC IFN gamma   62.4       HUVEC TNF alpha + IFN gamma   15.4       HUVEC TNF alpha + IL4   24.0       HUVEC IL-11   35.1       Lung Microvascular EC none   100.0       Lung Microvascular EC TNFalpha + IL-1beta   24.5       Microvascular Dermal EC none   18.0       Microsvasular Dermal EC TNFalpha + IL-1beta   20.0       Bronchial epithelium TNFalpha + IL1beta   31.2       Small airway epithelium none   7.2       Small airway epithelium TNFalpha + IL-1beta   49.0       Coronery artery SMC rest   54.3       Coronery artery SMC TNFalpha + IL-1beta   41.5       Astrocytes rest   20.4       Astrocytes TNFalpha + IL-1beta   14.1       KU-812 (Basophil) rest   96.6       KU-812 (Basophil) PMA/ionomycin   55.5       CCD1106 (Keratinocytes) none   49.3       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   7.6       Liver cirrhosis   1.9       NCI-H292 none   17.2       NCI-H292 IL-4   21.9       NCI-H292 IL-9   33.0       NCI-H292 IL-13   24.5       NCI-H292 IFN gamma   29.1       HPAEC none   15.1       HPAEC TNF alpha + IL-1 beta   39.2       Lung fibroblast none   54.7       Lung fibroblast TNF alpha + IL-1 beta   64.2       Lung fibroblast IL-4   32.1       Lung fibroblast IL-9   37.4       Lung fibroblast IL-13   37.4       Lung fibroblast IFN gamma   61.1       Dermal fibroblast CCD1070 rest   66.4       Dermal fibroblast CCD1070 TNF alpha   77.4       Dermal fibroblast CCD1070 IL-1 beta   44.4       Dermal fibroblast IFN gamma   20.3       Dermal fibroblast IL-4   74.7       Dermal Fibroblasts rest   20.3       Neutrophils TNFa + LPS   4.0       Neutrophils rest   0.0       Colon   0.0       Lung   0.0       Thymus   6.0       Kidney   16.8                    
     [0792]               TABLE PG                          Panel 4D                         Rel.Exp. (%)           Ag2022, Run       Tissue Name   160996807                             Secondary Th1 act   21.3       Secondary Th2 act   16.3       Secondary Tr1 act   0.0       Secondary Th1 rest   5.2       Secondary Th2 rest   6.7       Secondary Tr1 rest   6.3       Primary Th1 act   15.6       Primary Th2 act   12.9       Primary Tr1 act   20.2       Primary Th1 rest   23.2       Primary Th2 rest   11.4       Primary Tr1 rest   1.6       CD45RA CD4 lymphocyte act   12.7       CD45RO CD4 lymphocyte act   11.4       CD8 lymphocyte act   12.4       Secondary CD8 lymphocyte rest   12.0       Secondary CD8 lymphocyte act   11.4       CD4 lymphocyte none   3.2       2ry Th1/Th2/Tr1 anti-CD95 CH11   9.0       LAK cells rest   10.6       LAK cells IL-2   12.8       LAK cells IL-2 + IL-12   9.3       LAK cells IL-2 + IFN gamma   11.3       LAK cells IL-2 + IL-18   9.3       LAK cells PMA/ionomycin   5.8       NK Cells IL-2 rest   9.7       Two Way MLR 3 day   9.2       Two Way MLR 5 day   11.5       Two Way MLR 7 day   7.5       PBMC rest   3.9       PBMC PWM   24.7       PBMC PHA-L   12.6       Ramos (B cell) none   13.6       Ramos (B cell) ionomycin   32.3       B lymphocytes PWM   50.0       B lymphocytes CD40L and IL-4   25.5       EOL-1 dbcAMP   18.0       EOL-1 dbcAMP PMA/ionomycin   27.5       Dendritic cells none   10.1       Dendritic cells LPS   6.9       Dendritic cells anti-CD40   9.0       Monocytes rest   11.1       Monocytes LPS   7.0       Macrophages rest   12.5       Macrophages LPS   5.9       HUVEC none   22.2       HUVEC started   22.4       HUVEC IL-1beta   3.8       HUVEC IFN gamma   15.3       HUVEC TNF alpha + IFN gamma   13.4       HUVEC TNF alpha + IL4   13.7       HUVEC IL-11   13.8       Lung Microvascular EC none   14.9       Lung Microvascular EC TNFalpha + IL-1beta   18.0       Microvascular Dermal EC none   22.2       Microsvasular Dermal EC TNFalpha + IL-1 beta   18.8       Bronchial epithelium TNFalpha + IL1beta   5.8       Small airway epithelium none   6.9       Small airway epithelium TNFalpha + IL-1beta   25.2       Coronery artery SMC rest   18.6       Coronery artery SMC TNFalpha + IL-1beta   14.0       Astrocytes rest   12.6       Astrocytes TNFalpha + IL-1beta   15.5       KU-812 (Basophil) rest   58.6       KU-812 (Basophil) PMA/ionomycin   100.0       CCD1106 (Keratinocytes) none   14.3       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   1.7       Liver cirrhosis   1.6       Lupus kidney   1.4       NCI-H292 none   19.9       NCI-H292 IL-4   20.4       NCI-H292 IL-9   22.4       NCI-H292 IL-13   12.6       NCI-H292 IFN gamma   12.9       HPAEC none   16.4       HPAEC TNF alpha + IL-1 beta   17.6       Lung fibroblast none   23.0       Lung fibroblast TNF alpha + IL-1 beta   14.3       Lung fibroblast IL-4   30.8       Lung fibroblast IL-9   27.2       Lung fibroblast IL-13   19.6       Lung fibroblast IFN gamma   27.5       Dermal fibroblast CCD1070 rest   24.7       Dermal fibroblast CCD1070 TNF alpha   47.3       Dermal fibroblast CCD1070 IL-1 beta   21.5       Dermal fibroblast IFN gamma   12.5       Dermal fibroblast IL-4   22.5       IBD Colitis 2   0.8       IBD Crohn&#39;s   1.3       Colon   13.8       Lung   8.6       Thymus   9.9       Kidney   18.7                    
     [0793]               TABLE PH                          Panel 5 Islet                         Rel.Exp. (%)           Ag2022, Run       Tissue Name   296333462                             97457_Patient-02go_adipose   8.2       97476_Patient-07sk_skeletal muscle   0.0       97477_Patient-07ut_uterus   9.7       97478_Patient-07pl_placenta   10.0       99167_Bayer Patient 1   0.0       97482_Patient-08ut_uterus   7.3       97483_Patient-08pl_placenta   4.2       97486_Patient-09sk_skeletal muscle   10.7       97487_Patient-09ut_uterus   5.5       97488_Patient-09pl_placenta   4.5       97492_Patient-10ut_uterus   4.0       97493_Patient-10pl_placenta   12.8       97495_Patient-11go_adipose   3.3       97496_Patient-11sk_skeletal muscle   12.0       97497_Patient-11ut_uterus   11.0       97498_Patient-11pl_placenta   5.8       97500_Patient-12go_adipose   8.8       97501_Patient-12sk_skeletal muscle   33.4       97502_Patient-12ut_uterus   9.9       97503_Patient-12pl_placenta   20.9       94721_Donor 2 U - A_Mesenchymal Stem Cells   100.0       94722_Donor 2 U - B_Mesenchymal Stem Cells   63.3       94723_Donor 2 U - C_Mesenchymal Stem Cells   68.3       94709_Donor 2 AM - A_adipose   46.0       94710_Donor 2 AM - B_adipose   28.7       94711_Donor 2 AM - C_adipose   27.4       94712_Donor 2 AD - A_adipose   48.3       94713_Donor 2 AD - B_adipose   65.5       94714_Donor 2 AD - C_adipose   46.0       94742_Donor 3 U - A_Mesenchymal Stem Cells   22.4       94743_Donor 3 U - B_Mesenchymal Stem Cells   28.1       94730_Donor 3 AM - A_adipose   62.9       94731_Donor 3 AM - B_adipose   77.9       94732_Donor 3 AM - C_adipose   70.7       94733_Donor 3 AD - A_adipose   69.3       94734_Donor 3 AD - B adipose   57.8       94735_Donor 3 AD - C_adipose   17.1       77138_Liver_HepG2untreated   31.6       73556_Heart_Cardiac stromal cells (primary)   9.1       81735_Small Intestine   15.2       72409_Kidney_Proximal Convoluted Tubule   14.4       82685_Small intestine_Duodenum   5.4       90650_Adrenal_Adrenocortical adenoma   7.7       72410_Kidney_HRCE   35.1       72411_Kidney_HRE   12.4       73139_Uterus_Uterine smooth muscle cells   24.7                    
     [0794] General_screening_panel_v1.7 Summary: Ag7706 Highest expression of this gene is detected in ovarian cancer IGROV-1 cell line (CT=26.2). Moderate to highe 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, 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, melanoma and brain cancers.  
     [0795] 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.  
     [0796] In addition, this gene is expressed at high to moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, 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.  
     [0797] Panel 1.3D Summary: Ag2022 Two results using the same probe and primer set show results that are in excellent agreement, with highest expression of this gene in adult skeletal muscle (CTs=27). This gene also shows moderate expression in other tissues with metabolic function including adipose, adult and fetal heart and liver, adult skeletal muscle, pancreas, and the adrenal, thyroid, and pituitary glands. Expression is much lower in fetal skeletal muscle (CTs=30) relative to the adult tissue (CTs=27), which may implicate the expression of this gene in differentiation of skeletal muscle and thus suggests that expression of this gene could be used to differentiate between the adult and fetal phenotypes of this tissue. The pathway mediated by MAP kinase kinase (MAPKK) has been shown to influence myoblast proliferation (ref. 3) and both insulin and exercise stimulate signaling via this pathway in skeletal muscle (ref. 4). Insulin resistance in obese and diabetic subjects may in part be due to tumor necrosis factor alpha, whose effects are mediated through interference with the normal activation of MAPKK by insulin (ref. 5). In addition, exercise training significantly improves insulin-induced MAPKK activity in obese Zucker rats(ref. 6). This indicates that an activator of this kinase may be an effective pharmaceutical agent in the treatment of diabetes. Furthermore, activation of the MAPKK pathway is involved in adipocyte differentiation from preadipocytes in androgen deficiency (ref. 7). Therefore, a MAPKK antagonist may be a suitable pharmacological agent in the treatment of obesity in some cases.  
     [0798] This gene is expressed at higher levels in cell lines derived from melanoma, and kidney and lung cancers compared to the normal tissues and may play a role in cancers in these tissues. Thus, the expression of this gene could be useful as a marker or as a therapeutic for lung and kidney cancer as well as melanomas. In addition, therapeutic modulation of the activity of the gene product, through the use of peptides, chimeric molecules or small molecule drugs, may be useful in the therapy of these cancers.  
     [0799] This gene, a homolog of Mitogen Activated Protein Kinase Kinase, is expressed at high to moderate levels across the brain, with highest expression in the central nervous seen in the thalamus (CT=28.4). Mitogen Activated Protein Kinase Kinase is activated by Valproic acid, a drug that is used to treat both seizure disorders and bipolar depression. Valproic acid is believed to work by increasing neuronal production of GABA, the major inhibitory neurotransmitter in the brain. Selective activation of this kinase may therefore have therapeutic benefit in the treatment of seizure disorders, bipolar disorder, or in any other neurological/psychiatric condition believed to be caused by a GABA deficit (schizophrenia).  
     [0800] See Yuan P X, Huang L D, Jiang Y M, Gutkind J S, Manji H K, Chen G. (2001) The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growth. J Biol Chem. 276:31674-83. PMID: 11418608; Bulleit R F, Hsieh T. (2000) MEK inhibitors block BDNF-dependent and -independent expression of GABA(A) receptor subunit mRNAs in cultured mouse cerebellar granule neurons. Brain Res Dev Brain Res. 119:1-10. PMID: 10648867; Jones N C, Fedorov Y V, Rosenthal R S, Olwin BB. (2001) ERK1/2 is required for myoblast proliferation but is dispensable for muscle gene expression and cell fusion. J Cell Physiol. 186:104-15. PMID: 11147804; Wojtaszewski J F, Lynge J, Jakobsen A B, Goodyear L J, Richter E A. (1999) Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: metabolic implications. Am J. Physiol. 277(4 Pt 1):E724-32. PMID: 10516133; Begum N, Ragolia L, Srinivasan M. (1996) Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells. Eur J. Biochem. 238:214-20. PMID: 8665940; Osman A A, Hancock J, Hunt D G, Ivy J L, Mandarino L J. (2001) Exercise training increases ERK2 activity in skeletal muscle of obese Zucker rats. J Appl Physiol. 90:454-60. PMID: 11160042; and Lacasa D, Garcia E, Henriot D, Agli B, Giudicelli Y. (1997) Site-related specificities of the control by androgenic status of adipogenesis and mitogen-activated protein kinase cascade/c-fos signaling pathways in rat preadipocytes. Endocrinology 138:3181-6. PMID: 9231766.  
     [0801] Panel 2.2 Summary: Ag2022 Highest expression of this gene in this panel is seen in a breast cancer sample (CT=29.0). The expression of this gene shows an association with samples derived from breast and kidney cancers when compared to the matched normal tissue. Thus, expression of the AC011005_da2 gene could be useful as a marker for breast and kidney cancers. Furthermore, therapeutic activity of the product of this gene, through the use of peptides, chimeric molecules or small molecule drugs, may be useful in the treatment of breast and kidney cancers.  
     [0802] Panel 4.1D Summary: Ag7706 Highest expression of this gene is detected in resting lung microvascular cells (CT=33.6). Low expression of this gene is also seen in resting and activated dermal and lung fibroblasts, resting keratinocytes, coronery artery SMC, activated small airway epithelium, resting dendritic cells and eosinophils, resting and activated HUVEC cells, activated B lymphocytes and Ramos B cells, resting IL-2 treated NK cells, activated naive and memory T cells, activated primary and secondary polarized T cells. Therefore, therapeutic modulation of this gene product may ameliorate symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis  
     [0803] Panel 4D Summary: Ag2022 Expression of this gene is ubiquitous throughout this panel. Highest expression of this gene is found in the basophil cell line, KU-812, upon activation with PMA/ionomycin (CT=26.2), compared to non-activated cells. High expression of this gene is also found on activated B cells, a B cell line, and dermal fibroblasts. This gene is homologous to a Mitogen Activated Protein Kinase Kinase 2 (MAPKK2), a serine threonine kinase which functions downstream of Raf in the signaling pathway that affects proliferation and differentiation. The high expression of this kinase on basophiles suggests a role for this kinase in mast cell/basophile signal transduction. Activated mast/basophile cells have been associated with many atopic diseases, including asthma, atopic contact dermatitis, allergies, and rhinitis. Therefore, therapeutic modulation of the expression or function of this gene product, through the use of small molecule drugs, might be beneficial in the treatment of these diseases. In addition, the high expression of this kinase in activated B cells suggests that the use of small molecule drugs designed to the this gene product could prevent B cell hyperproliferative disorders such as autoimmune diseases and lymphomas.  
     [0804] Panel 5 Islet Summary: Ag2022 This gene shows wide spread expression with highest expression seen in mesenchymal stem cells (CT=28.7). Expression of this gene is higher in undifferentiated and differentiated adipose tissue. Expression of this gene is detected in skeletal muscle, adipose tissue, uterus, placenta, kidney and small intestine. TNF alpha is one of the key factors involved in obesity-associated insulin resistance and is known to activate MEK1/2. Recently, it has been shown that inhibition of MEK1/2 restores insulin sensitivity induced by TNFalpha (Mol. Endocrinology, 2000, 14, 1557; J. Cell Physiol., 1999, 179,58). Thus, an antagonist of MEK2 should be beneficial for the treatment insulin resistance/diabetes.  
     [0805] Q. CG55838-04: Dual Specificity Mitogen-Activated Protein Kinase Kinase 2.  
     [0806] Expression of gene CG55838-04 was assessed using the primer-probe sets Ag2022 and Ag7822, described in Tables QA and QB. Results of the RTQ-PCR runs are shown in Tables QC, QD, QE, QF and QG. Please note that CG55838-04 represents a full-length physical clone.  
               TABLE OA                          Probe Name Ag2022                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-ccaggagtttgtcaataaatgc-3′   22   976   211               Probe   TET-5′-ctcatcaagaacccagcggagcg-3′-TAMRA   23   998   212               Reverse   5′-ttyatgaaggtgtggtttgtg-3′   21   1039   213                  
 
     [0807]               TABLE OB                          Probe Name Ag7822                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-ccaacatcctcgtgaactctaga-3′   23   606   214               Probe   TET-5′-aaccgctccggcccgaagtcaca-3′-TAMRA   23   644   215               Reverse   5′-gtccgactgcaccgagtaa-3′   19   679   216                    
     [0808]               TABLE QC                          General_screening_panel_v1.7                                 Rel.Exp. (%)               Ag7822, Run           Tissue Name   319066239                                         Adipose   7.9           HUVEC   44.4           Melanoma* Hs688(A).T   0.0           Melanoma* Hs688(B).T   8.2           Melanoma (met) SK-MEL-5   2.4           Testis   2.9           Prostate ca. (bone met) PC-3   3.3           Prostate ca. DU145   62.9           Prostate pool   2.8           Uterus pool   0.7           Ovarian ca. OVCAR-3   15.5           Ovarian ca. (ascites) SK-OV-3   0.0           Ovarian ca. OVCAR-4   11.9           Ovarian ca. OVCAR-5   2.6           Ovarian ca. IGROV-1   67.8           Ovarian ca. OVCAR-8   60.3           Ovary   13.2           Breast ca. MCF-7   14.0           Breast ca. MDA-MB-231   79.6           Breast ca. BT-549   18.3           Breast ca. T47D   77.9           Breast pool   2.0           Trachea   9.2           Lung   8.5           Fetal Lung   10.4           Lung ca. NCI-N417   30.8           Lung ca. LX-1   21.8           Lung ca. NCI-H146   12.2           Lung ca. SHP-77   28.9           Lung ca. NCI-H23   3.6           Lung ca. NCI-H460   3.1           Lung ca. HOP-62   100.0           Lung ca. NCI-H522   5.6           Lung ca. DMS-114   9.7           Liver   0.6           Fetal Liver   4.7           Kidney pool   7.1           Fetal Kidney   7.9           Renal ca. 786-0   1.9           Renal ca. A498   9.9           Renal ca. ACHN   2.3           Renal ca. UO-31   1.6           Renal ca. TK-10   5.3           Bladder   4.9           Gastric ca. (liver met.) NCI-N87   0.6           Stomach   0.0           Colon ca. SW-948   2.0           Colon ca. SW480   1.7           Colon ca. (SW480 met) SW620   28.9           Colon ca. HT29   33.4           Colon ca. HCT-116   69.3           Colon cancer tissue   0.0           Colon ca. SW1116   3.2           Colon ca. Colo-205   9.7           Colon ca. SW-48   4.6           Colon   1.2           Small Intestine   0.6           Fetal Heart           Heart   0.5           Lymph Node pool 1   2.9           Lymph Node pool 2   16.0           Fetal Skeletal Muscle   2.8           Skeletal Muscle pool   2.8           Skeletal Muscle   55.9           Spleen   1.2           Thymus   4.0           CNS cancer (glio/astro) SF-268   4.2           CNS cancer (glio/astro) T98G   1.0           CNS cancer (neuro; met) SK-N-AS   0.0           CNS cancer (astro) SF-539   11.3           CNS cancer (astro) SNB-75   61.1           CNS cancer (glio) SNB-19   5.9           CNS cancer (glio) SF-295   20.6           Brain (Amygdala)   12.6           Brain (Cerebellum)   31.4           Brain (Fetal)   12.2           Brain (Hippocampus)   13.0           Cerebral Cortex pool   18.8           Brain (Substantia nigra)   14.6           Brain (Thalamus)   11.0           Brain (Whole)   18.6           Spinal Cord   17.6           Adrenal Gland   1.3           Pituitary Gland   21.9           Salivary Gland   0.6           Thyroid   3.4           Pancreatic ca. PANC-1   31.9           Pancreas pool   4.2                        
     [0809]               TABLE QD                          Panel 1.3D                             Rel. Exp. (%)   Rel. Exp. (%)           Ag2022, Run   Ag2022, Run       Tissue Name   165626371   165627116                                 Liver adenocarcinoma   23.2   15.8       Pancreas   9.6   4.3       Pancreatic ca. CAPAN2   4.1   4.4       Adrenal gland   8.0   10.3       Thyroid   12.1   9.6       Salivary gland   10.9   5.9       Pituitary gland   12.0   9.6       Brain (fetal)   13.6   7.6       Brain (whole)   47.3   25.0       Brain (amygdala)   33.7   19.9       Brain (cerebellum)   33.2   16.3       Brain (hippocampus)   42.6   21.6       Brain (Substantia nigra)   30.6   13.8       Brain (thalamus)   50.3   24.5       Cerebral Cortex   36.6   31.4       Spinal cord   16.8   8.7       glio/astro U87-MG   17.6   18.4       glio/astro U-118-MG   54.7   38.4       astrocytoma SW1783   13.5   12.8       neuro*; met SK-N-AS   15.4   12.9       astrocytoma SF-539   14.3   9.4       astrocytoma SNB-75   29.5   25.7       glioma SNB-19   23.7   17.8       glioma U251   38.4   34.4       glioma SF-295   18.4   17.2       Heart (fetal)   17.2   16.3       Heart   25.7   10.2       Skeletal muscle (fetal)   12.2   12.9       Skeletal muscle   100.0   100.0       Bone marrow   15.0   14.5       Thymus   7.6   8.1       Spleen   14.5   11.4       Lymph node   25.7   19.2       Colorectal   6.7   4.7       Stomach   14.5   10.0       Small intestine   30.1   32.3       Colon ca. SW480   9.2   6.7       Colon ca.* SW620(SW480 met)   3.1   4.1       Colon ca. HT29   1.4   2.5       Colon ca. HCT-116   8.5   9.1       Colon ca. CaCo-2   5.6   7.0       Colon ca. tissue(ODO3866)   11.8   11.5       Colon ca. HCC-2998   4.6   7.2       Gastric ca.* (liver met)   13.0   9.3       NCI-N87       Bladder   3.4   4.2       Trachea   13.7   10.4       Kidney   14.6   6.3       Kidney (fetal)   9.2   4.2       Renal ca. 786-0   9.5   7.3       Renal ca. A498   23.2   19.3       Renal ca. RXF 393   16.8   15.9       Renal ca. ACHN   14.4   10.5       Renal ca. UO-31   11.2   8.1       Renal ca. TK-10   5.4   4.8       Liver   11.2   3.4       Liver (fetal)   24.1   18.7       Liver ca.   12.8   9.9       (hepatoblast) HepG2       Lung   11.4   11.8       Lung (fetal)   11.8   8.9       Lung ca. (small cell) LX-1   12.4   8.4       Lung ca. (small cell) NCI-H69   15.8   17.0       Lung ca. (s. cell var.)   11.3   12.6       SHP-77       Lung ca. (large   30.6   28.3       cell)NCI-H460       Lung ca. (non-sm. cell) A549   5.7   6.2       Lung ca. (non-s. cell)   6.3   7.0       NCI-H23       Lung ca. (non-s. cell)   13.1   12.0       HOP-62       Lung ca. (non-s. cl)   5.7   4.5       NCI-H522       Lung ca. (squam.) SW 900   3.6   4.1       Lung ca. (squam.) NCI-H596   12.2   11.0       Mammary gland   7.2   8.8       Breast ca.* (pl. ef) MCF-7   9.6   9.1       Breast ca.* (pl. ef)   47.0   56.6       MDA-MB-231       Breast ca.* (pl. ef) T47D   4.7   4.6       Breast ca. BT-549   19.6   20.6       Breast ca. MDA-N   6.3   6.2       Ovary   7.3   6.4       Ovarian ca. OVCAR-3   7.4   5.6       Ovarian ca. OVCAR-4   27.9   20.6       Ovarian ca, OVCAR-5   7.0   7.0       Ovarian ca. OVCAR-8   11.7   9.8       Ovarian ca. IGROV-1   3.5   2.3       Ovarian ca.* (ascites)   23.7   17.0       SK-OV-3       Uterus   25.9   18.7       Placenta   10.9   6.3       Prostate   10.5   10.4       Prostate ca.* (bone   20.4   18.0       met)PC-3       Testis   27.2   19.3       Melanoma Hs688(A).T   6.6   5.1       Melanoma* (met) Hs688(B).T   10.7   8.5       Melanoma UACC-62   43.5   36.1       Melanoma M14   42.0   36.9       Melanoma LOX IMVI   8.0   9.0       Melanoma* (met) SK-MEL-5   15.9   14.2       Adipose   4.8   3.8                    
     [0810]               TABLE QE                          Panel 2.2                                 Rel.Exp. (%)               Ag2022, Run           Tissue Name   174232815                                         Normal Colon   24.7           Colon cancer (OD06064)   14.4           Colon Margin (OD06064)   18.0           Colon cancer (OD06159)   12.2           Colon Margin (OD06159)   18.2           Colon cancer (OD06297-04)   15.5           Colon Margin (OD06297-05)   23.7           CC Gr.2 ascend colon (ODO3921)   25.7           CC Margin (ODO3921)   21.9           Colon cancer metastasis (OD06104)   6.0           Lung Margin (OD06104)   19.6           Colon mets to lung (OD04451-01)   30.1           Lung Margin (OD04451-02)   11.4           Normal Prostate   21.9           Prostate Cancer (OD04410)   9.1           Prostate Margin (OD04410)   11.2           Normal Ovary   58.2           Ovarian cancer (OD06283-03)   12.9           Ovarian Margin (OD06283-07)   8.5           Ovarian Cancer 064008   15.8           Ovarian cancer (OD06145)   19.2           Ovarian Margin (OD06145)   34.4           Ovarian cancer (OD06455-03)   11.0           Ovarian Margin (OD06455-07)   2.8           Normal Lung   11.3           Invasive poor diff. lung adeno (ODO4945-01   19.1           Lung Margin (ODO4945-03)   9.9           Lung Malignant Cancer (OD03126)   22.4           Lung Margin (OD03126)   8.6           Lung Cancer (OD05014A)   24.5           Lung Margin (OD05014B)   13.8           Lung cancer (OD06081)   12.4           Lung Margin (OD06081)   2.6           Lung Cancer (OD04237-01)   14.5           Lung Margin (OD04237-02)   29.7           Ocular Melanoma Metastasis   44.4           Ocular Melanoma Margin (Liver)   12.2           Melanoma Metastasis   32.5           Melanoma Margin (Lung)   13.2           Normal Kidney   14.9           Kidney Ca, Nuclear grade 2 (OD04338)   40.9           Kidney Margin (OD04338)   12.3           Kidney Ca Nuclear grade 1/2 (OD04339)   49.3           Kidney Margin (OD04339)   17.9           Kidney Ca, Clear cell type (OD04340)   21.0           Kidney Margin (OD04340)   18.0           Kidney Ca, Nuclear grade 3 (OD04348)   16.6           Kidney Margin (OD04348)   70.7           Kidney malignant cancer (OD06204B)   22.1           Kidney normal adjacent tissue (OD06204E)   18.7           Kidney Cancer (OD04450-01)   48.3           Kidney Margin (OD04450-03)   16.6           Kidney Cancer 8120613   14.1           Kidney Margin 8120614   40.6           Kidney Cancer 9010320   20.4           Kidney Margin 9010321   12.9           Kidney Cancer 8120607   48.0           Kidney Margin 8120608   37.9           Normal Uterus   11.9           Uterine Cancer 064011   16.7           Normal Thyroid   9.7           Thyroid Cancer 064010   19.1           Thyroid Cancer A302152   28.3           Thyroid Margin A302153   11.8           Normal Breast   12.3           Breast Cancer (OD04566)   12.9           Breast Cancer 1024   23.2           Breast Cancer (OD04590-01)   46.0           Breast Cancer Mets (OD04590-03)   35.6           Breast Cancer Metastasis (OD04655-05)   100.0           Breast Cancer 064006   19.3           Breast Cancer 9100266   8.3           Breast Margin 9100265   9.3           Breast Cancer A209073   3.6           Breast Margin A2090734   22.1           Breast cancer (OD06083)   47.3           Breast cancer node metastasis (OD06083)   49.0           Normal Liver   29.3           Liver Cancer 1026   31.2           Liver Cancer 1025   39.2           Liver Cancer 6004-T   36.1           Liver Tissue 6004-N   8.1           Liver Cancer 6005-T   74.2           Liver Tissue 6005-N   74.2           Liver Cancer 064003   45.7           Normal Bladder   19.3           Bladder Cancer 1023   29.9           Bladder Cancer A302173   31.0           Normal Stomach   48.6           Gastric Cancer 9060397   16.5           Stomach Margin 9060396   33.2           Gastric Cancer 9060395   14.6           Stomach Margin 9060394   34.4           Gastric Cancer 064005   25.3                        
     [0811]               TABLE QF                          Panel 4D                         Rel.Exp. (%)           Ag2022, Run       Tissue Name   160996807                             Secondary Th1 act   21.3       Secondary Th2 act   16.3       Secondary Tr1 act   0.0       Secondary Th1 rest   5.2       Secondary Th2 rest   6.7       Secondary Tr1 rest   6.3       Primary Th1 act   15.6       Primary Th2 act   12.9       Primary Tr1 act   20.2       Primary Th1 rest   23.2       Primary Th2 rest   11.4       Primary Tr1 rest   1.6       CD45RA CD4 lymphocyte act   12.7       CD45RO CD4 lymphocyte act   11.4       CD8 lymphocyte act   12.4       Secondary CD8 lymphocyte rest   12.0       Secondary CD8 lymphocyte act   11.4       CD4 lymphocyte none   3.2       2ry Th1/Th2/Tr1 anti-CD95 CH11   9.0       LAK cells rest   10.6       LAK cells IL-2   12.8       LAK cells IL-2 + IL-12   9.3       LAK cells IL-2 + IFN gamma   11.3       LAK cells IL-2 + IL-18   9.3       LAK cells PMA/ionomycin   5.8       NK Cells IL-2 rest   9.7       Two Way MLR 3 day   9.2       Two Way MLR 5 day   11.5       Two Way MLR 7 day   7.5       PBMC rest   3.9       PBMC PWM   24.7       PBMC PHA-L   12.6       Ramos (B cell) none   13.6       Ramos (B cell) ionomycin   32.3       B lymphocytes PWM   50.0       B lymphocytes CD40L and IL-4   25.5       EOL-1 dbcAMP   18.0       EOL-1 dbcAMP PMA/ionomycin   27.5       Dendritic cells none   10.1       Dendritic cells LPS   6.9       Dendritic cells anti-CD40   9.0       Monocytes rest   11.1       Monocytes LPS   7.0       Macrophages rest   12.5       Macrophages LPS   5.9       HUVEC none   22.2       HUVEC starved   22.4       HUVEC IL-1beta   3.8       HUVEC IFN gamma   15.3       HUVEC TNF alpha + IFN gamma   13.4       HUVEC TNF alpha + IL4   13.7       HUVEC IL-11   13.8       Lung Microvascular EC none   14.9       Lung Microvascular EC TNFalpha + IL-1beta   18.0       Microvascular Dermal EC none   22.2       Microsvasular Dermal EC TNFalpha + IL-1beta   18.8       Bronchial epithelium TNFalpha + IL1beta   5.8       Small airway epithelium none   6.9       Small airway epithelium TNFalpha + IL-1beta   25.2       Coronery artery SMC rest   18.6       Coronery artery SMC TNFalpha + IL-1beta   14.0       Astrocytes rest   12.6       Astrocytes TNFalpha + IL-1beta   15.5       KU-812 (Basophil) rest   58.6       KU-812 (Basophil) PMA/ionomycin   100.0       CCD1106 (Keratinocytes) none   14.3       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   1.7       Liver cirrhosis   1.6       Lupus kidney   1.4       NCI-H292 none   19.9       NCI-H292 IL-4   20.4       NCI-H292 IL-9   22.4       NCI-H292 IL-13   12.6       NCI-H292 IFN gamma   12.9       HPAEC none   16.4       HPAEC TNF alpha + IL-1 beta   17.6       Lung fibroblast none   23.0       Lung fibroblast TNF alpha + IL-1 beta   14.3       Lung fibroblast IL-4   30.8       Lung fibroblast IL-9   27.2       Lung fibroblast IL-13   19.6       Lung fibroblast IFN gamma   27.5       Dermal fibroblast CCD1070 rest   24.7       Dermal fibroblast CCD1070 TNF alpha   47.3       Dermal fibroblast CCD1070 IL-1 beta   21.5       Dermal fibroblast IFN gamma   12.5       Dermal fibroblast IL-4   22.5       IBD Colitis 2   0.8       IBD Crohn&#39;s   1.3       Colon   13.8       Lung   8.6       Thymus   9.9       Kidney   18.7                    
     [0812]               TABLE QG                          Panel 5 Islet                             Rel. Exp. (%)   Rel. Exp. (%)           Ag2022, Run   Ag7822, Run       Tissue Name   296333462   319961194                                 97457_Patient-02go_adipose   8.2   1.7       97476_Patient-07sk_skeletal   0.0   0.0       muscle       97477_Patient-07ut_uterus   9.7   0.0       97478_Patient-07pl_placenta   10.0   3.0       99167_Bayer Patient 1   0.0   24.0       97482_Patient-08ut_uterus   7.3   0.0       97483_Patient-08pl_placenta   4.2   7.0       97486_Patient-09sk_skeletal   10.7   18.3       muscle       97487_Patient-09ut_uterus   5.5   0.0       97488_Patient-09pl_placenta   4.5   3.9       97492_Patient-10ut_uterus   4.0   4.0       97493_Patient-10pl_placenta   12.8   0.0       97495_Patient-11go_adipose   3.3   0.0       97496_Patient-11sk_skeletal   12.0   1.7       muscle       97497_Patient-11ut_uterus   11.0   6.6       97498_Patient-11pl_placenta   5.8   0.0       97500_Patient-12go_adipose   8.8   0.0       97501_Patient-12sk_skeletal   33.4   9.9       muscle       97502_Patient-12ut_uterus   9.9   0.0       97503_Patient-12pl_placenta   20.9   1.5       94721_Donor 2 U -   100.0   31.0       A_Mesenchymal Stem Cells       94722_Donor 2 U -   63.3   50.0       B_Mesenchymal Stem Cells       94723_Donor 2 U -   68.3   27.0       C_Mesenchymal Stem Cells       94709_Donor 2 AM - A_adipose   46.0   81.2       94710_Donor 2 AM - B_adipose   28.7   4.7       94711_Donor 2 AM - C_adipose   27.4   8.4       94712_Donor 2 AD - A_adipose   48.3       94713_Donor 2 AD - B_adipose   65.5   16.8       94714_Donor2 AD - C_adipose   46.0   17.9       94742_Donor 3 U -   22.4   14.7       A_Mesenchymal Stem Cells       94743_Donor 3 U -   28.1   2.4       B_Mesenchymal Stem Cells       94730_Donor 3 AM - A_adipose   62.9   0.0       94731_Donor 3 AM - B_adipose   77.9   2.4       94732_Donor 3 AM - C_adipose   70.7   3.7       94733_Donor 3 AD - A_adipose   69.3   100.0       94734_Donor 3 AD - B_adipose   57.8   0.0       94735_Donor 3 AD - C_adipose   17.1   0.0       77138 Liver HepG2untreated   31.6   10.4       73556_Heart_Cardiac   9.1   0.0       stromal cells (primary)       81735_Small Intestine   15.2   0.0       72409_Kidney_Proximal   14.4   0.0       Convoluted Tubule       82685_Small intestine_Duodenum   5.4   17.9       90650_Adrenal_Adrenocortical   7.7   0.0       adenoma       72410_Kidney_HRCE   35.1   11.7       72411_Kidney_HRE   12.4   0.0       73139_Uterus_Uterine   24.7   15.5       smooth muscle cells                    
     [0813] General_screening_panel_v1.7 Summary: Ag7822 Highest expression of this gene is detected in lung cancer HOP-62 cell line (CT=29.5). Moderate expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, 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, melanoma and brain cancers.  
     [0814] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, thyroid, pituitary gland, skeletal muscle, and fetal liver. 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.  
     [0815] In addition, this gene is expressed at moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer&#39;s disease, Parkinson&#39;s disease, epilepsy, multiple sclerosis, schizophrenia and depression.  
     [0816] Panel 1.3D Summary: Ag2022 Two results using the same probe and primer set show results that are in excellent agreement, with highest expression of this gene in adult skeletal muscle (CTs=27). This gene also shows moderate expression in other tissues with metabolic function including adipose, adult and fetal heart and liver, adult skeletal muscle, pancreas, and the adrenal, thyroid, and pituitary glands. Expression is much lower in fetal skeletal muscle (CTs=30) relative to the adult tissue (CTs=27), which may implicate the expression of this gene in differentiation of skeletal muscle and thus suggests that expression of this gene could be used to differentiate between the adult and fetal phenotypes of this tissue. The pathway mediated by MAP kinase kinase (MAPKK) has been shown to influence myoblast proliferation (ref. 3) and both insulin and exercise stimulate signaling via this pathway in skeletal muscle (ref. 4). Insulin resistance in obese and diabetic subjects may in part be due to tumor necrosis factor alpha, whose effects are mediated through interference with the normal activation of MAPKK by insulin (ref. 5). In addition, exercise training significantly improves insulin-induced MAPKK activity in obese Zucker rats(ref. 6). This indicates that an activator of this kinase may be an effective pharmaceutical agent in the treatment of diabetes. Furthermore, activation of the MAPKK pathway is involved in adipocyte differentiation from preadipocytes in androgen deficiency (ref. 7). Therefore, a MAPKK antagonist may be a suitable pharmacological agent in the treatment of obesity in some cases.  
     [0817] This gene is expressed at higher levels in cell lines derived from melanoma, and kidney and lung cancers compared to the normal tissues and may play a role in cancers in these tissues. Thus, the expression of this gene could be useful as a marker or as a therapeutic for lung and kidney cancer as well as melanomas. In addition, therapeutic modulation of the activity of the gene product, through the use of peptides, chimeric molecules or small molecule drugs, may be useful in the therapy of these cancers.  
     [0818] This gene, a homolog of Mitogen Activated Protein Kinase Kinase, is expressed at high to moderate levels across the brain, with highest expression in the central nervous seen in the thalamus (CT=28.4). Mitogen Activated Protein Kinase Kinase is activated by Valproic acid, a drug that is used to treat both seizure disorders and bipolar depression. Valproic acid is believed to work by increasing neuronal production of GABA, the major inhibitory neurotransmitter in the brain. Selective activation of this kinase may therefore have therapeutic benefit in the treatment of seizure disorders, bipolar disorder, or in any other neurological/psychiatric condition believed to be caused by a GABA deficit (schizophrenia).  
     [0819] See Yuan P X, Huang L D, Jiang Y M, Gutkind J S, Manji H K, Chen G. (2001) The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growth. J Biol Chem. 276:31674-83. PMID: 11418608; Bulleit R F, Hsieh T. (2000) MEK inhibitors block BDNF-dependent and independent expression of GABA(A) receptor subunit mRNAs in cultured mouse cerebellar granule neurons. Brain Res Dev Brain Res. 119:1-10. PMID: 10648867; Jones N C, Fedorov Y V, Rosenthal R S, Olwin B B. (2001) ERK1/2 is required for myoblast proliferation but is dispensable for muscle gene expression and cell fusion. J Cell Physiol. 186:104-15. PMID: 11147804; Wojtaszewski J F, Lynge J, Jakobsen A B, Goodyear L J, Richter E A. (1999) Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: metabolic implications. Am J Physiol. 277(4 Pt 1):E724-32. PMID: 10516133; Begum N, Ragolia L, Srinivasan M. (1996) Effect of tumor necrosis factor-alpha on insulin-stimulated mitogen-activated protein kinase cascade in cultured rat skeletal muscle cells. Eur J. Biochem. 238:214-20. PMID: 8665940; Osman A A, Hancock J, Hunt D G, Ivy J L, Mandarino L J. (2001) Exercise training increases ERK2 activity in skeletal muscle of obese Zucker rats. J Appl Physiol. 90:454-60. PMID: 11160042; and Lacasa D, Garcia E, Henriot D, Agli B, Giudicelli Y. (1997) Site-related specificities of the control by androgenic status of adipogenesis and mitogen-activated protein kinase cascade/c-fos signaling pathways in rat preadipocytes. Endocrinology 138:3181-6. PMID: 9231766.  
     [0820] Panel 2.2 Summary: Ag2022 Highest expression of this gene in this panel is seen in a breast cancer sample (CT=29.0). The expression of this gene shows an association with samples derived from breast and kidney cancers when compared to the matched normal tissue. Thus, expression of the AC011005_da2 gene could be useful as a marker for breast and kidney cancers. Furthermore, therapeutic activity of the product of this gene, through the use of peptides, chimeric molecules or small molecule drugs, may be useful in the treatment of breast and kidney cancers.  
     [0821] Panel 4D Summary: Ag2022 Expression of this gene is ubiquitous throughout this panel. Highest expression of this gene is found in the basophil cell line, KU-812, upon activation with PMA/ionomycin (CT=26.2), compared to non-activated cells. High expression of this gene is also found on activated B cells, a B cell line, and dermal fibroblasts. This gene is homologous to a Mitogen Activated Protein Kinase Kinase 2 (MAPKK2), a serine threonine kinase which functions downstream of Raf in the signaling pathway that affects proliferation and differentiation. The high expression of this kinase on basophiles suggests a role for this kinase in mast cell/basophile signal transduction. Activated mast/basophile cells have been associated with many atopic diseases, including asthma, atopic contact dermatitis, allergies, and rhinitis. Therefore, therapeutic modulation of the expression or function of this gene product, through the use of small molecule drugs, might be beneficial in the treatment of these diseases. In addition, the high expression of this kinase in activated B cells suggests that the use of small molecule drugs designed to the this gene product could prevent B cell hyperproliferative disorders such as autoimmune diseases and lymphomas.  
     [0822] Panel 5 Islet Summary: Ag2022 This gene shows wide spread expression with highest expression seen in mesenchymal stem cells (CT=28.7). Expression of this gene is higher in undifferentiated and differentiated adipose tissue. Expression of this gene is detected in skeletal muscle, adipose tissue, uterus, placenta, kidney and small intestine. TNF alpha is one of the key factors involved in obesity-associated insulin resistance and is known to activate MEK1/2. Recently, it has been shown that inhibition of MEK1/2 restores insulin sensitivity induced by TNFalpha (Mol. Endocrinology, 2000, 14, 1557; J. Cell Physiol., 1999, 179,58). Thus, an antagonist of MEK2 should be beneficial for the treatment insulin resistance/diabetes.  
     [0823] Ag7822 Highest expression of this gene is detected in a differentiated adipose tissue (CT=33.9). Low expression of this gene is also seen in midway differentiated adipose tissue.  
     [0824] R. CG56618-04: Heat Shock Protein HSP90.  
     [0825] Expression of gene CG56618-04 was assessed using the primer-probe set Ag4548, described in Table RA. Results of the RTQ-PCR runs are shown in Tables RB, RC and RD.  
               TABLE RA                          Probe Name Ag4548                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-ggtgtggttgactctgaggat-3′   21   1228   217               Probe   TET-5′-tgaacatctcccgagaaatgctccag-3′-TAMRA   26   1256   218               Reverse   5′-ttgcgaatgactttcaagattt-3′   22   1289   219                  
 
     [0826]               TABLE RB                          CNS_neurodegeneration_v1.0                                 Rel.Exp. (%)               Ag4548, Run           Tissue Name   224721638                                         AD 1 Hippo   19.8           AD 2 Hippo   31.2           AD 3 Hippo   11.9           AD 4 Hippo   5.2           AD 5 Hippo   75.8           AD 6 Hippo   72.2           Control 2 Hippo   32.3           Control 4 Hippo   9.5           Control (Path) 3 Hippo   9.3           AD 1 Temporal Ctx   13.0           AD 2 Temporal Ctx   34.2           AD 3 Temporal Ctx   7.1           AD 4 Temporal Ctx   18.8           AD 5 Inf Temporal Ctx   88.3           AD 5 Sup Temporal Ctx   51.4           AD 6 Inf Temporal Ctx   68.3           AD 6 Sup Temporal Ctx   56.3           Control 1 Temporal Ctx   5.1           Control 2 Temporal Ctx   61.6           Control 3 Temporal Ctx   13.8           Control 3 Temporal Ctx   6.9           Control (Path) 1 Temporal Ctx   68.8           Control (Path) 2 Temporal Ctx   41.2           Control (Path) 3 Temporal Ctx   5.1           Control (Path) 4 Temporal Ctx   29.7           AD 1 Occipital Ctx   17.1           AD 2 Occipital Ctx (Missing)   0.0           AD 3 Occipital Ctx   11.7           AD 4 Occipital Ctx   12.2           AD 5 Occipital Ctx   59.9           AD 6 Occipital Ctx   36.1           Control 1 Occipital Ctx   5.2           Control 2 Occipital Ctx   81.8           Control 3 Occipital Ctx   15.1           Control 4 Occipital Ctx   5.2           Control (Path) 1 Occipital Ctx   100.0           Control (Path) 2 Occipital Ctx   9.2           Control (Path) 3 Occipital Ctx   3.6           Control (Path) 4 Occipital Ctx   12.3           Control 1 Parietal Ctx   6.8           Control 2 Parietal Ctx   42.6           Control 3 Parietal Ctx   22.8           Control (Path) 1 Parietal Ctx   92.7           Control (Path) 2 Parietal Ctx   16.8           Control (Path) 3 Parietal Ctx   4.6           Control (Path) 4 Parietal Ctx   39.2                        
     [0827]               TABLE RC                          General_screening_panel_v1.4                                 Rel. Exp. (%)               Ag4548, Run           Tissue Name   222809448                                         Adipose   4.4           Melanoma* Hs688(A).T   8.4           Melanoma* Hs688(B).T   8.0           Melanoma* M14   27.7           Melanoma* LOXIMVI   38.7           Melanoma* SK-MEL-5   49.7           Squamous cell carcinoma SCC-4   15.6           Testis Pool   2.9           Prostate ca.* (bone met) PC-3   16.6           Prostate Pool   2.7           Placenta   1.5           Uterus Pool   1.6           Ovarian ca. OVCAR-3   16.0           Ovarian ca. SK-OV-3   28.5           Ovarian ca. OVCAR-4   14.6           Ovarian ca. OVCAR-5   16.5           Ovarian ca. IGROV-1   12.2           Ovarian ca. OVCAR-8   6.7           Ovary   5.5           Breast ca. MCF-7   13.8           Breast ca. MDA-MB-231   39.2           Breast ca. BT 549   37.6           Breast ca. T47D   30.1           Breast ca. MDA-N   20.3           Breast Pool   5.8           Trachea   4.5           Lung   0.6           Fetal Lung   9.4           Lung ca. NCI-N417   6.6           Lung ca. LX-1   19.6           Lung ca. NCI-H146   15.8           Lung ca. SHP-77   31.4           Lung ca. A549   20.3           Lung ca. NCI-H526   6.6           Lung ca. NCI-H23   31.2           Lung ca. NCI-H460   13.2           Lung ca. HOP-62   17.4           Lung ca. NCI-H522   16.8           Liver   0.9           Fetal Liver   7.2           Liver ca. HepG2   21.9           Kidney Pool   8.2           Fetal Kidney   5.0           Renal ca. 786-0   13.7           Renal ca. A498   6.8           Renal ca. ACHN   9.9           Renal ca. UO-31   19.2           Renal ca. TK-10   27.0           Bladder   7.0           Gastric ca. (liver met.) NCI-N87   18.8           Gastric ca. KATO III   51.1           Colon ca. SW-948   11.9           Colon ca. SW480   37.9           Colon ca.* (SW480 met) SW620   28.9           Colon ca. HT29   18.3           Colon ca. HCT-116   100.0           Colon ca. CaCo-2   20.3           Colon cancer tissue   10.5           Colon ca. SW1116   6.9           Colon ca. Colo-205   2.8           Colon ca. SW-48   9.1           Colon Pool   6.4           Small Intestine Pool   5.9           Stomach Pool   4.3           Bone Marrow Pool   2.0           Fetal Heart   3.0           Heart Pool   3.6           Lymph Node Pool   5.5           Fetal Skeletal Muscle   2.4           Skeletal Muscle Pool   10.5           Spleen Pool   4.3           Thymus Pool   4.2           CNS cancer (glio/astro) U87-MG   20.6           CNS cancer (glio/astro) U-118-MG   27.5           CNS cancer (neuro; met) SK-N-AS   24.5           CNS cancer (astro) SF-539   14.9           CNS cancer (astro) SNB-75   28.5           CNS cancer (glio) SNB-19   13.4           CNS cancer (glio) SF-295   27.2           Brain (Amygdala) Pool   6.1           Brain (cerebellum)   6.4           Brain (fetal)   9.2           Brain (Hippocampus) Pool   6.0           Cerebral Cortex Pool   9.4           Brain (Substantia nigra) Pool   9.2           Brain (Thalamus) Pool   11.7           Brain (whole)   10.4           Spinal Cord Pool   4.8           Adrenal Gland   11.8           Pituitary gland Pool   2.4           Salivary Gland   1.7           Thyroid (female)   3.9           Pancreatic ca. CAPAN2   8.4           Pancreas Pool   6.9                        
     [0828]               TABLE RD                          Panel 4.1D                         Rel. Exp. (%)           Ag4548, Run       Tissue Name   198485557                             Secondary Th1 act   82.4       Secondary Th2 act   90.8       Secondary Tr1 act   82.9       Secondary Th1 rest   7.1       Secondary Th2 rest   12.8       Secondary Tr1 rest   11.3       Primary Th1 act   76.8       Primary Th2 act   95.3       Primary Tr1 act   100.0       Primary Th1 rest   11.6       Primary Th2 rest   6.0       Primary Tr1 rest   14.4       CD45RA CD4 lymphocyte act   75.8       CD45RO CD4 lymphocyte act   90.1       CD8 lymphocyte act   85.3       Secondary CD8 lymphocyte rest   82.4       Secondary CD8 lymphocyte act   47.6       CD4 lymphocyte none   13.1       2ry Th1/Th2/Tr1_anti-CD95 CH11   12.6       LAK cells rest   38.7       LAK cells IL-2   52.9       LAK cells IL-2 + IL-12   55.9       LAK cells IL-2 + IFN gamma   42.0       LAK cells IL-2 + IL-18   46.0       LAK cells PMA/ionomycin   94.6       NK Cells IL-2 rest   49.3       Two Way MLR 3 day   46.3       Two Way MLR 5 day   62.4       Two Way MLR 7 day   0.0       PBMC rest   13.2       PBMC PWM   90.8       PBMC PHA-L   73.2       Ramos (B cell) none   85.3       Ramos (B cell) ionomycin   78.5       B lymphocytes PWM   68.8       B lymphocytes CD40L and IL-4   49.7       EOL-1 dbcAMP   55.9       EOL-1 dbcAMP PMA/ionomycin   57.0       Dendritic cells none   37.9       Dendritic cells LPS   24.0       Dendritic cells anti-CD40   34.2       Monocytes rest   13.2       Monocytes LPS   31.9       Macrophages rest   43.2       Macrophages LPS   16.5       HUVEC none   60.3       HUVEC starved   74.2       HUVEC IL-1beta   70.2       HUVEC IFN gamma   51.1       HUVEC TNF alpha + IFN gamma   45.1       HUVEC TNF alpha + IL4   58.6       HUVEC IL-11   39.8       Lung Microvascular EC none   57.0       Lung Microvascular EC TNFalpha + IL-1beta   43.8       Microvascular Dermal EC none   44.1       Microsvasular Dermal EC TNFalpha + IL-1beta   39.5       Bronchial epithelium TNFalpha + IL1beta   44.4       Small airway epithelium none   37.1       Small airway epithelium TNFalpha + IL-1beta   46.7       Coronery artery SMC rest   42.6       Coronery artery SMC TNFalpha + IL-1beta   43.2       Astrocytes rest   33.4       Astrocytes TNFalpha + IL-1beta   27.7       KU-812 (Basophil) rest   79.6       KU-812 (Basophil) PMA/ionomycin   100.0       CCD1106 (Keratinocytes) none   53.6       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   44.4       Liver cirrhosis   18.9       NCI-H292 none   42.9       NCI-H292 IL-4   68.8       NCI-H292 IL-9   64.6       NCI-H292 IL-13   61.6       NCI-H292 IFN gamma   54.3       HPAEC none   51.8       HPAEC TNF alpha + IL-1 beta   64.6       Lung fibroblast none   44.1       Lung fibroblast TNF alpha + IL-1 beta   35.1       Lung fibroblast IL-4   53.6       Lung fibroblast IL-9   62.9       Lung fibroblast IL-13   56.3       Lung fibroblast IFN gamma   61.1       Dermal fibroblast CCD1070 rest   64.6       Dermal fibroblast CCD1070 TNF alpha   62.0       Dermal fibroblast CCD1070 IL-1 beta   46.7       Dermal fibroblast IFN gamma   40.6       Dermal fibroblast IL-4   52.5       Dermal Fibroblasts rest   35.6       Neutrophils TNFa + LPS   14.3       Neutrophils rest   9.4       Colon   12.1       Lung   24.0       Thymus   25.5       Kidney   33.7                    
     [0829] CNS_neurodegeneration_v1.0 Summary: Ag4548 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer&#39;s diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential role of this gene in treatment of central nervous system disorders.  
     [0830] General_screening_panel_v1.4 Summary: Ag4548 Highest expression of this gene is detected in a colon cancer HCT-116 cell line (CT=23.2). High levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.  
     [0831] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to 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.  
     [0832] 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.  
     [0833] Interestingly, this gene is expressed at much higher levels in fetal (CTs=26-27) when compared to adult lung and liver (CTs=30). This observation suggests that expression of this gene can be used to distinguish fetal from adult lung and liver. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance lung and liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of lung and liver related diseases.  
     [0834] Panel 4.1D Summary: Ag4548 Highest expression of this gene is detected in activated primary Tr1 cells (CT=27.3). This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     [0835] S. CG57509-01: Calpain 3.  
     [0836] Expression of gene CG57509-01 was assessed using the primer-probe set Ag2073, described in Table SA. Results of the RTQ-PCR runs are shown in Tables SB and SC.  
               TABLE SA                          Probe Name Ag2073                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-acccaagtggcatctattcag-3′   21   2234   220               Probe   TET-5′-tcagccgcaattttcctattatcgga-3′-TAMRA   26   2202   221               Reverse   5′-gtgaagttgctcgaatgtcttc-3′   22   2172   222                  
 
     [0837]               TABLE SB                          Panel 1.3D                                 Rel. Exp. (%)               Ag2073, Run           Tissue Name   165627447                                         Liver adenocarcinoma   0.0           Pancreas   0.1           Pancreatic ca. CAPAN 2   0.0           Adrenal gland   0.1           Thyroid   0.5           Salivary gland   0.3           Pituitary gland   0.3           Brain (fetal)   0.0           Brain (whole)   0.7           Brain (amygdala)   0.4           Brain (cerebellum)   0.5           Brain (hippocampus)   0.8           Brain (substantia nigra)   0.3           Brain (thalamus)   0.5           Cerebral Cortex   0.2           Spinal cord   0.6           glio/astro U87-MG   0.0           glio/astro U-118-MG   0.2           astrocytoma SW1783   0.0           neuro*; met SK-N-AS   0.0           astrocytoma SF-539   0.0           astrocytoma SNB-75   0.0           glioma SNB-19   0.1           glioma U251   0.4           glioma SF-295   0.0           Heart (fetal)   0.1           Heart   0.3           Skeletal muscle (fetal)   7.7           Skeletal muscle   100.0           Bone marrow   2.0           Thymus   0.2           Spleen   0.4           Lymph node   1.0           Colorectal   0.2           Stomach   0.4           Small intestine   0.9           Colon ca. SW480   0.0           Colon ca.* SW620(SW480 met)   0.0           Colon ca. HT29   0.0           Colon ca. HCT-116   0.0           Colon ca. CaCo-2   0.0           Colon ca. tissue(ODO3866)   0.0           Colon ca. HCC-2998   0.0           Gastric ca.* (liver met) NCI-N87   0.8           Bladder   0.1           Trachea   0.3           Kidney   0.5           Kidney (fetal)   0.1           Renal ca. 786-0   0.1           Renal ca. A498   0.1           Renal ca. RXF 393   0.0           Renal ca. ACHN   0.0           Renal ca. UO-31   0.0           Renal ca. TK-10   0.1           Liver   0.3           Liver (fetal)   0.3           Liver ca. (hepatoblast) HepG2   0.0           Lung   0.4           Lung (fetal)   0.4           Lung ca. (small cell) LX-1   0.2           Lung ca. (small cell) NCI-H69   0.0           Lung ca. (s. cell var.) SHP-77   0.0           Lung ca. (large cell)NCI-H460   0.0           Lung ca. (non-sm. cell) A549   0.0           Lung ca. (non-s. cell) NCI-H23   0.1           Lung ca. (non-s. cell) HOP-62   0.0           Lung ca. (non-s. cl) NCI-H522   0.0           Lung ca. (squam.) SW 900   0.0           Lung ca. (squam.) NCI-H596   0.0           Mammary gland   0.3           Breast ca.* (pl. ef) MCF-7   0.0           Breast ca.* (pl. ef) MDA-MB-231   0.1           Breast ca.* (pl. ef) T47D   0.0           Breast ca. BT-549   0.1           Breast ca. MDA-N   0.0           Ovary   0.0           Ovarian ca. OVCAR-3   0.1           Ovarian ca. OVCAR-4   0.0           Ovarian ca. OVCAR-5   0.1           Ovarian ca. OVCAR-8   0.0           Ovarian ca. IGROV-1   0.0           Ovarian ca.* (ascites) SK-OV-3   0.2           Uterus   0.6           Placenta   0.1           Prostate   0.3           Prostate ca.* (bone met)PC-3   0.1           Testis   0.8           Melanoma Hs688(A).T   0.0           Melanoma* (met) Hs688(B).T   0.0           Melanoma UACC-62   0.1           Melanoma M14   0.1           Melanoma LOX IMVI   0.0           Melanoma* (met) SK-MEL-5   0.0           Adipose   0.5                        
     [0838]               TABLE SC                          Panel 5D                         Rel. Exp. (%)           Ag2073, Run       Tissue Name   169269384                             97457_Patient-02go_adipose   0.7       97476_Patient-07sk_skeletal muscle   7.9       97477_Patient-07ut_uterus   0.0       97478_Patient-07pl_placenta   0.2       97481_Patient-08sk_skeletal muscle   8.7       97482_Patient-08ut_uterus   0.1       97483_Patient-08pl_placenta   0.1       97486_Patient-09sk_skeletal muscle   14.1       97487_Patient-09ut_uterus   0.1       97488_Patient-09pl_placenta   0.1       97492_Patient-10ut_uterus   0.3       97493_Patient-10pl_placenta   0.1       97495_Patient-11go_adipose   0.2       97496_Patient-11sk_skeletal muscle   82.9       97497_Patient-11ut_uterus   0.1       97498_Patient-11pl_placenta   0.3       97500_Patient-12go_adipose   0.5       97501_Patient-12sk_skeletal muscle   100.0       97502_Patient-12ut_uterus   0.3       97503_Patient-12pl_placenta   0.1       94721_Donor 2 U - A_Mesenchymal Stem Cells   0.2       94722_Donor 2 U - B_Mesenchymal Stem Cells   0.0       94723_Donor 2 U - C_Mesenchymal Stem Cells   0.4       94709_Donor 2 AM - A_adipose   0.2       94710_Donor 2 AM - B_adipose   0.1       94711_Donor 2 AM - C_adipose   0.0       94712_Donor 2 AD - A_adipose   0.0       94713_Donor 2 AD - B_adipose   0.7       94714_Donor 2 AD - C_adipose   0.3       94742_Donor 3 U - A_Mesenchymal Stem Cells   0.0       94743_Donor 3 U - B_Mesenchymal Stem Cells   0.0       94730_Donor 3 AM - A_adipose   0.1       94731_Donor 3 AM - B_adipose   0.2       94732_Donor 3 AM - C_adipose   0.2       94733_Donor 3 AD - A_adipose   0.2       94734_Donor 3 AD - B_adipose   0.0       94735_Donor 3 AD - C_adipose   0.2       77138_Liver_HepG2untreated   0.0       73556_Heart_Cardiac stromal cells (primary)   0.2       81735_Small Intestine   0.4       72409_Kidney_Proximal Convoluted Tubule   0.2       82685 Small intestine_Duodenum   0.4       90650_Adrenal_Adrenocortical adenoma   0.1       72410_Kidney_HRCE   0.3       72411_Kidney_HRE   0.1       73139 Uterus_Uterine smooth muscle cells   0.1                    
     [0839] Panel 1.3D Summary: Ag2073 The CG57909-01 gene, a calpain homolog, has low levels of expression in thyroid, pituitary, heart, adipose and liver. Calpain 10 was recently identified as a susceptibility gene for type 2 diabetes. Thus, this gene product may be a small molecule target for the treatment of endocrine and metabolic disease, including the thyroidopathies, Types 1 and 2 diabetes and obesity. In addition, this gene is highly expressed in skeletal muscle. Mutations in the calpain 3 gene have been proven to be responsible for limb-girdle muscular dystrophy (LGMD) type 2A. Thus, therapeutic modulation of this gene product may be a treatment for LGMD type 2A.  
     [0840] See Chae J, Minami N, Jin Y, Nakagawa M, Murayama K, Igarashi F, Nonaka 1. Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle muscular dystrophy. Neuromuscul Disord. September 2001;11(6-7):547-55. PMID: 11525884; and Huang Y, Wang KK. The calpain family and human disease. Trends Mol Med. August 2001; 7(8):355-62. Review. PMID: 11516996.  
     [0841] Panel 4D Summary: Ag2073 Results from one experiment with the CG56003-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.  
     [0842] Panel 5D Summary: Ag2073 Expression of the CG57509-01 gene is restricted to skeletal muscle, confirming the results from Panel 1.3D. Please see Panel 1.3D for discussion of this gene in metabolic disease.  
     [0843] T. CG90474-02: Mitochondrial Uncoupling Protein 2.  
     [0844] Expression of gene CG90474-02 was assessed using the primer-probe set Ag1693, described in Table TA. Results of the RTQ-PCR runs are shown in Tables TB and TC. Please note that CG90474-02 represents a full-length physical clone.  
               TABLE TA                          Probe Name Ag1693                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-cctactgccactgtgaagtttc-3′   22   154   223               Probe   TET-5′-tcgcagatctcatcacctttcctctg-3′-TAMRA   26   200   224               Reverse   5′-ggatctgtaaccggactttagc-3′   22   232   225                  
 
     [0845]               TABLE TB                          Panel 1.3D                                 Rel. Exp. (%)               Agl693, Run           Tissue Name   157637343                                         Liver adenocarcinoma   14.6           Pancreas   0.9           Pancreatic ca. CAPAN 2   4.7           Adrenal gland   6.2           Thyroid   15.2           Salivary gland   7.2           Pituitary gland   3.5           Brain (fetal)   0.8           Brain (whole)   1.7           Brain (amygdala)   3.2           Brain (cerebellum)   0.5           Brain (hippocampus)   7.6           Brain (substantia nigra)   1.5           Brain (thalamus)   2.5           Cerebral Cortex   3.1           Spinal cord   4.2           glio/astro U87-MG   2.3           glio/astro U-118-MG   8.1           astrocytoma SW1783   2.6           neuro*; met SK-N-AS   6.3           astrocytoma SF-539   0.4           astrocytoma SNB-75   3.3           glioma SNB-19   0.4           glioma U251   0.8           glioma SF-295   0.6           Heart (fetal)   18.4           Heart   1.5           Skeletal muscle (fetal)   100.0           Skeletal muscle   11.1           Bone marrow   48.0           Thymus   28.7           Spleen   50.3           Lymph node   21.9           Colorectal   13.8           Stomach   7.3           Small intestine   11.1           Colon ca. SW480   8.1           Colon ca.* SW620(SW480 met)   5.8           Colon ca. HT29   18.0           Colon ca. HCT-116   1.6           Colon ca. CaCo-2   15.1           Colon ca. tissue(ODO3866)   6.2           Colon ca. HCC-2998   7.1           Gastric ca.* (liver met) NCI-N87   33.9           Bladder   1.5           Trachea   52.1           Kidney   1.7           Kidney (fetal)   13.2           Renal ca. 786-0   16.2           Renal ca. A498   29.7           Renal ca. RXF 393   0.2           Renal ca. ACHN   3.1           Renal ca. UO-31   0.5           Renal ca. TK-10   6.0           Liver   1.6           Liver (fetal)   55.5           Liver ca. (hepatoblast) HepG2   4.7           Lung   20.6           Lung (fetal)   11.3           Lung ca. (small cell) LX-1   3.7           Lung ca. (small cell) NCI-H69   26.1           Lung ca. (s. cell var.) SHP-77   54.3           Lung ca. (large cell)NCI-H460   0.1           Lung ca. (non-sm. cell) A549   6.7           Lung ca. (non-s. cell) NCI-H23   13.5           Lung ca. (non-s. cell) HOP-62   0.6           Lung ca. (non-s. cl) NCI-H522   3.4           Lung ca. (squam.) SW 900   2.7           Lung ca. (squam.) NCI-H596   12.1           Mammary gland   18.0           Breast ca.* (pl. ef) MCF-7   17.1           Breast ca.* (pl. ef) MDA-MB-231   41.8           Breast ca.* (pl. ef) T47D   9.1           Breast ca. BT-549   26.8           Breast ca. MDA-N   4.3           Ovary   22.5           Ovarian ca. OVCAR-3   3.3           Ovarian ca. OVCAR-4   11.1           Ovarian ca. OVCAR-5   1.5           Ovarian ca. OVCAR-8   11.4           Ovarian ca. IGROV-1   4.9           Ovarian ca.* (ascites) SK-OV-3   3.5           Uterus   1.6           Placenta   5.8           Prostate   4.2           Prostate ca.* (bone met)PC-3   3.2           Testis   5.4           Melanoma Hs688(A).T   0.4           Melanoma* (met) Hs688(B).T   0.1           Melanoma UACC-62   0.0           Melanoma M14   0.9           Melanoma LOX IMVI   0.2           Melanoma* (met) SK-MEL-5   0.7           Adipose   8.4                        
     [0846]               TABLE TC                          Panel 5D                         Rel. Exp. (%)           Agl693, Run       Tissue Name   166510712                             97457 Patient-02go adipose   27.7       97476_Patient-07sk_skeletal muscle   19.3       97477_Patient-07ut_uterus   9.1       97478_Patient-07pl_placenta   16.3       97481_Patient-08sk_skeletal muscle   8.4       97482_Patient-08ut_uterus   8.8       97483_Patient-08pl_placenta   15.2       97486_Patient-09sk_skeletal muscle   7.9       97487_Patient-09ut_uterus   5.8       97488_Patient-09pl_placenta   7.5       97492_Patient-10ut_uterus   11.8       97493_Patient-10pl_placenta   32.3       97495_Patient-11go_adipose   49.7       97496_Patient-11sk_skeletal muscle   30.8       97497_Patient-11ut_uterus   26.8       97498_Patient-11pl_placenta   15.2       97500_Patient-12go_adipose   55.5       97501_Patient-12sk_skeletal muscle   56.3       97502_Patient-12ut_uterus   18.0       97503_Patient-12pl_placenta   19.5       94721_Donor2 U - A_Mesenchymal Stem Cells   0.5       94722_Donor2 U - B_Mesenchymal Stem Cells   0.3       94723_Donor 2 U - C_Mesenchymal Stem Cells   0.8       94709_Donor 2 AM - A_adipose   1.7       94710_Donor 2 AM - B_adipose   0.7       94711_Donor 2 AM - C_adipose   0.3       94712_Donor 2 AD - A_adipose   11.5       94713_Donor 2 AD - B_adipose   17.3       94714_Donor 2 AD - C_adipose   10.6       94742_Donor 3 U - A_Mesenchymal Stem Cells   0.4       94743_Donor 3 U - B_Mesenchymal Stem Cells   1.1       94730_Donor 3 AM - A_adipose   1.8       94731_Donor 3 AM - B_adipose   0.4       94732_Donor 3 AM - C_adipose   0.5       94733_Donor 3 AD - A_adipose   5.0       94734_Donor 3 AD - B_adipose   3.3       94735_Donor 3 AD - C_adipose   4.1       77138_Liver_HepG2untreated   23.5       73556_Heart_Cardiac stromal cells (primary)   2.0       81735_Small Intestine   32.5       72409_Kidney_Proximal Convoluted Tubule   5.3       82685_Small intestine_Duodenum   25.2       90650_Adrenal_Adrenocortical adenoma   4.8       72410_Kidney_HRCE   60.3       72411_Kidney_HRE   100.0       73139_Uterus_Uterine smooth muscle cells   0.6                    
     [0847] Panel 1.3D Summary: Ag1693 Highest expression of this gene is seen in skeletal muscle (CT=26.2). This gene is also expressed at low but significant levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.  
     [0848] In addition, this gene is expressed at much higher levels in fetal heart, liver and skeletal muscle tissue (CTs=26-28) 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. In addition, the relative overexpression of this gene in fetal heart, liver, and skeletal muscle suggests that the protein product may enhance the growth or development of these organs in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of liver, heart, and muscle related diseases.  
     [0849] This gene is widely expressed in this panel, with moderate to 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.  
     [0850] This gene is also expressed at moderate to 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.  
     [0851] Panel 5D Summary: Ag1693 Highest expression is seen in a kidney cell line (CT=28.7). Moderate levels of expression are also seen in metabolic tissues such as adipose, placenta, and skeletal muscle. Please see Panel 1.3D for discussion of this gene in metabolic disease.  
     [0852] U. CG159399-01: CRAL/TRIO Containing Protein.  
     [0853] Expression of gene CG159399-01 was assessed using the primer-probe set Ag2893, described in Table UA. Results of the RTQ-PCR runs are shown in Tables UB, UC, UD, UE and UF.  
               TABLE UA                          Probe Name Ag2893                                             Start   SEQ       Primers   Sequences   Length   Position   ID No                                         Forward   5′-gcccaatcctgatgactacttc-3′   22   39   226               Probe   TET-5′-ctccaagctcggagctttgacctg-3′-TAMRA   24   73   227               Reverse   5′-ctcagcatgtcctctgatttct-3′   22   98   228                  
 
     [0854]               TABLE UB                          CNS_neurodegeneration_v1.0                                 Rel. Exp. (%)               Ag2893, Run           Tissue Name   224116295                                         AD 1 Hippo   18.6           AD 2 Hippo   59.0           AD 3 Hippo   25.3           AD 4 Hippo   56.3           AD 5 Hippo   95.9           AD 6 Hippo   86.5           Control 2 Hippo   26.1           Control 4 Hippo   59.5           Control (Path) 3 Hippo   17.3           AD 1 Temporal Ctx   48.6           AD 2 Temporal Ctx   61.1           AD 3 Temporal Ctx   25.2           AD 4 Temporal Ctx   70.7           AD 5 Inf Temporal Ctx   100.0           AD 5 Sup Temporal Ctx   55.9           AD 6 Inf Temporal Ctx   86.5           AD 6 Sup Temporal Ctx   92.7           Control 1 Temporal Ctx   24.7           Control 2 Temporal Ctx   53.2           Control 3 Temporal Ctx   26.8           Control 3 Temporal Ctx   40.6           Control (Path) 1 Temporal Ctx   63.7           Control (Path) 2 Temporal Ctx   44.1           Control (Path) 3 Temporal Ctx   15.8           Control (Path) 4 Temporal Ctx   43.5           AD 1 Occipital Ctx   41.8           AD 2 Occipital Ctx (Missing)   0.0           AD 3 Occipital Ctx   27.5           AD 4 Occipital Ctx   58.6           AD 5 Occipital Ctx   47.0           AD 6 Occipital Ctx   31.2           Control 1 Occipital Ctx   20.9           Control 2 Occipital Ctx   63.7           Control 3 Occipital Ctx   62.0           Control 4 Occipital Ctx   28.1           Control (Path) 1 Occipital Ctx   82.9           Control (Path) 2 Occipital Ctx   24.5           Control (Path) 3 Occipital Ctx   15.0           Control (Path) 4 Occipital Ctx   28.3           Control 1 Parietal Ctx   20.4           Control 2 Parietal Ctx   55.1           Control 3 Parietal Ctx   30.4           Control (Path) 1 Parietal Ctx   74.2           Control (Path) 2 Parietal Ctx   35.8           Control (Path) 3 Parietal Ctx   6.9           Control (Path) 4 Parietal Ctx   38.4                        
     [0855]               TABLE UC                          Panel 1.3D                             Rel. Exp. (%)   Rel. Exp. (%)           Ag2893, Run   Ag2893, Run       Tissue Name   160944329   165701489                                 Liver adenocarcinoma   0.0   0.0       Pancreas   2.5   4.0       Pancreatic ca. CAPAN 2   0.0   0.0       Adrenal gland   0.8   1.2       Thyroid   0.5   0.3       Salivary gland   0.0   0.0       Pituitary gland   2.0   1.8       Brain (fetal)   0.9   2.0       Brain (whole)   3.6   6.3       Brain (amygdala)   3.6   6.1       Brain (cerebellum)   6.3   6.2       Brain (hippocampus)   9.3   10.4       Brain (Substantia nigra)   2.6   5.4       Brain (thalamus)   7.2   13.8       Cerebral Cortex   25.5   3.3       Spinal cord   17.0   10.7       glio/astro U87-MG   0.0   0.0       glio/astro U-118-MG   0.0   0.0       astrocytoma SW1783   0.6   0.0       neuro*; met SK-N-AS   0.0   0.0       astrocytoma SF-539   0.0   0.0       astrocytoma SNB-75   0.0   0.0       glioma SNB-19   0.0   0.0       glioma U251   0.0   0.0       glioma SF-295   0.0   0.0       Heart (fetal)   1.4   0.0       Heart   0.0   0.0       Skeletal muscle (fetal)   3.3   0.0       Skeletal muscle   0.4   0.0       Bone marrow   0.0   0.3       Thymus   1.4   0.2       Spleen   1.7   0.6       Lymph node   0.0   1.1       Colorectal   0.0   0.0       Stomach   0.0   2.0       Small intestine   0.0   2.3       Colon ca. SW480   2.3   0.5       Colon ca.* SW620(SW480 met)   0.0   0.6       Colon ca. HT29   0.0   0.0       Colon ca. HCT-116   0.0   0.0       Colon ca. CaCo-2   0.9   0.0       Colon ca. tissue(ODO3866)   1.5   0.0       Colon ca. HCC-2998   0.0   0.0       Gastric ca.* (liver met)   0.0   0.6       NCI-N87       Bladder   11.3   5.0       Trachea   2.5   0.0       Kidney   26.2   5.3       Kidney (fetal)   19.5   4.3       Renal ca. 786-0   73.7   64.2       Renal ca. A498   0.5   0.6       Renal ca. RXF 393   100.0   100.0       Renal ca. ACHN   28.1   18.8       Renal ca. UO-31   23.5   24.3       Renal ca. TK-10   21.2   8.9       Liver   0.0   1.3       Liver (fetal)   1.2   1.6       Liver ca. (hepatoblast)   10.9   8.1       HepG2       Lung   8.9   4.8       Lung (fetal)   6.6   3.6       Lung ca. (small cell) LX-1   0.0   0.0       Lung ca. (small cell)   0.0   0.0       NCI-H69       Lung ca. (s. cell var.)   0.0   0.0       SHP-77       Lung ca. (large cell)   0.0   0.0       NCI-H460       Lung ca. (non-sm. cell)   0.0   0.0       A549       Lung ca. (non-s. cell)   2.3   1.1       NCI-H23       Lung ca. (non-s. cell)   3.6   2.5       HOP-62       Lung ca. (non-s. cl)   0.0   0.0       NCI-H522       Lung ca. (squam.) SW 900   0.0   2.4       Lung ca. (squam.) NCI-H596   0.8   0.0       Mammary gland   0.5   0.0       Breast ca.* (pl. ef)   0.0   0.0       MCF-7       Breast ca.* (pl. ef)   0.4   1.7       MDA-MB-231       Breast ca.* (pl. ef)   4.8   0.9       T47D       Breast ca. BT-549   0.0   0.0       Breast ca. MDA-N   0.0   0.0       Ovary   9.9   2.4       Ovarian ca. OVCAR-3   3.2   2.2       Ovarian ca. OVCAR-4   0.0   0.0       Ovarian ca. OVCAR-5   0.0   0.0       Ovarian ca. OVCAR-8   1.0   1.2       Ovarian ca. IGROV-1   0.0   0.0       Ovarian ca.* (ascites)   0.0   0.0       SK-OV-3       Uterus   1.9   5.4       Placenta   0.5   0.9       Prostate   1.0   1.0       Prostate ca.* (bone met)   0.0   0.0       PC-3       Testis   25.7   9.3       Melanoma Hs688(A).T   0.0   0.0       Melanoma* (met) Hs688(B).T   0.0   0.0       Melanoma UACC-62   0.0   0.0       Melanoma M14   0.0   0.0       Melanoma LOX IMVI   0.0   0.0       Melanoma* (met) SK-MEL-5   0.0   0.0       Adipose   1.0   0.0                    
     [0856]               TABLE UD                          Panel 2D                         Rel. Exp. (%)           Ag2893, Run       Tissue Name   160966072                             Normal Colon   2.5       CC Well to Mod Diff (ODO3866)   0.0       CC Margin (ODO3866)   0.5       CC Gr.2 rectosigmoid (ODO3868)   0.0       CC Margin (ODO3868)   0.0       CC Mod Diff (ODO3920)   0.5       CC Margin (ODO3920)   0.4       CC Gr.2 ascend colon (ODO3921)   0.5       CC Margin (ODO3921)   0.0       CC from Partial Hepatectomy (ODO4309) Mets   0.7       Liver Margin (ODO4309)   0.9       Colon mets to lung (OD04451-01)   5.0       Lung Margin (OD04451-02)   18.0       Normal Prostate 6546-1   0.7       Prostate Cancer (OD04410)   2.0       Prostate Margin (OD04410)   8.7       Prostate Cancer (OD04720-01)   3.8       Prostate Margin (OD04720-02)   3.5       Normal Lung 061010   12.9       Lung Met to Muscle (ODO4286)   0.0       Muscle Margin (ODO4286)   0.3       Lung Malignant Cancer (OD03126)   8.7       Lung Margin (OD03126)   21.0       Lung Cancer (OD04404)   8.0       Lung Margin (OD04404)   28.7       Lung Cancer (OD04565)   0.7       Lung Margin (OD04565)   33.0       Lung Cancer (OD04237-01)   1.3       Lung Margin (OD04237-02)   11.3       Ocular Mel Met to Liver (ODO4310)   0.0       Liver Margin (ODO4310)   0.4       Melanoma Mets to Lung (OD04321)   1.0       Lung Margin (OD04321)   32.1       Normal Kidney   42.0       Kidney Ca, Nuclear grade 2 (OD04338)   55.5       Kidney Margin (OD04338)   40.9       Kidney Ca Nuclear grade 1/2 (OD04339)   61.1       Kidney Margin (OD04339)   22.8       Kidney Ca, Clear cell type (OD04340)   100.0       Kidney Margin (OD04340)   31.9       Kidney Ca, Nuclear grade 3 (OD04348)   3.3       Kidney Margin (OD04348)   27.0       Kidney Cancer (OD04622-01)   30.4       Kidney Margin (OD04622-03)   17.4       Kidney Cancer (OD04450-01)   21.5       Kidney Margin (OD04450-03)   21.3       Kidney Cancer 8120607   70.7       Kidney Margin 8120608   16.8       Kidney Cancer 8120613   0.0       Kidney Margin 8120614   18.0       Kidney Cancer 9010320   74.7       Kidney Margin 9010321   18.3       Normal Uterus   0.7       Uterus Cancer 064011   10.8       Normal Thyroid   0.0       Thyroid Cancer 064010   1.7       Thyroid Cancer A302152   3.4       Thyroid Margin A302153   0.0       Normal Breast   2.0       Breast Cancer (OD04566)   0.2       Breast Cancer (OD04590-01)   0.2       Breast Cancer Mets (OD04590-03)   0.8       Breast Cancer Metastasis (OD04655-05)   0.6       Breast Cancer 064006   0.3       Breast Cancer 1024   0.5       Breast Cancer 9100266   0.5       Breast Margin 9100265   1.1       Breast Cancer A209073   0.2       Breast Margin A209073   0.4       Normal Liver   0.0       Liver Cancer 064003   0.8       Liver Cancer 1025   0.4       Liver Cancer 1026   8.1       Liver Cancer 6004-T   1.2       Liver Tissue 6004-N   0.0       Liver Cancer 6005-T   5.4       Liver Tissue 6005-N   0.3       Normal Bladder   17.3       Bladder Cancer 1023   0.2       Bladder Cancer A302173   1.3       Bladder Cancer (OD04718-01)   7.9       Bladder Normal Adjacent (OD04718-03)   0.4       Normal Ovary   2.0       Ovarian Cancer 064008   10.7       Ovarian Cancer (OD04768-07)   0.3       Ovary Margin (OD04768-08)   4.2       Normal Stomach   3.1       Gastric Cancer 9060358   0.4       Stomach Margin 9060359   1.1       Gastric Cancer 9060395   0.2       Stomach Margin 9060394   3.0       Gastric Cancer 9060397   0.2       Stomach Margin 9060396   2.6       Gastric Cancer 064005   0.8                    
     [0857]               TABLE UE                          Panel 3D                         Rel. Exp. (%)           Ag2893, Run       Tissue Name   165924139                             Daoy- Medulloblastoma   2.0       TE671- Medulloblastoma   0.0       D283 Med- Medulloblastoma   0.0       PFSK-1- Primitive Neuroectodermal   0.0       XF-498- CNS   0.0       SNB-78- Glioma   0.0       SF-268- Glioblastoma   0.9       T98G- Glioblastoma   0.0       SK-N-SH- Neuroblastoma (metastasis)   0.0       SF-295- Glioblastoma   0.0       Cerebellum   6.4       Cerebellum   9.9       NCI-H292- Mucoepidermoid lung carcinoma   2.0       DMS-114- Small cell lung cancer   0.0       DMS-79- Small cell lung cancer   1.4       NCI-H146- Small cell lung cancer   0.0       NCI-H526- Small cell lung cancer   4.5       NCI-N417- Small cell lung cancer   0.0       NCI-H82- Small cell lung cancer   0.0       NCI-H157- Squamous cell lung cancer   0.0       (metastasis)       NCI-HI 155- Large cell lung cancer   0.0       NCI-H1299- Large cell lung cancer   0.0       NCI-H727- Lung carcinoid   0.0       NCI-UMC-11- Lung carcinoid   0.0       LX-1- Small cell lung cancer   0.0       Colo-205- Colon cancer   0.0       KM12- Colon cancer   0.0       KM20L2- Colon cancer   0.0       NCI-H716- Colon cancer   0.0       SW-48- Colon adenocarcinoma   0.0       SW1116- Colon adenocarcinoma   0.0       LS 174T- Colon adenocarcinoma   0.0       SW-948- Colon adenocarcinoma   0.0       SW-480- Colon adenocarcinoma   0.0       NCI-SNU-5- Gastric carcinoma   9.7       KATO III- Gastric carcinoma   0.0       NCI-SNU-16- Gastric carcinoma   0.0       NCI-SNU-1- Gastric carcinoma   0.0       RF-1- Gastric adenocarcinoma   0.0       RF-48- Gastric adenocarcinoma   0.0       MKN-45- Gastric carcinoma   0.0       NCI-N87- Gastric carcinoma   0.0       OVCAR-5- Ovarian carcinoma   0.0       RL95-2- Uterine carcinoma   0.0       HelaS3- Cervical adenocarcinoma   0.0       Ca Ski- Cervical epidermoid carcinoma   0.0       (metastasis)       ES-2- Ovarian clear cell carcinoma   0.0       Ramos- Stimulated with PMA/ionomycin 6 h   0.0       Ramos- Stimulated with PMA/ionomycin 14 h   0.0       MEG-01- Chronic myelogenous leukemia   0.0       (megokaryoblast)       Raji- Burkitt&#39;s lymphoma   0.0       Daudi- Burkitt&#39;s lymphoma   0.0       U266- B-cell plasmacytoma   0.0       CA46- Burkitt&#39;s lymphoma   0.0       RL- non-Hodgkin&#39;s B-cell lymphoma   0.0       JM1- pre-B-cell lymphoma   0.0       Jurkat- T cell leukemia   0.0       TF-1- Erythroleukemia   0.0       HUT 78- T-cell lymphoma   0.0       U937- Histiocytic lymphoma   0.0       KU-812- Myelogenous leukemia   0.0       769-P- Clear cell renal carcinoma   7.7       Caki-2- Clear cell renal carcinoma   100.0       SW 839- Clear cell renal carcinoma   73.2       Rhabdoid kidney tumor   0.0       Hs766T- Pancreatic carcinoma (LN metastasis)   0.0       CAPAN-1- Pancreatic adenocarcinoma   5.3       (liver metastasis)       SU86.86- Pancreatic carcinoma (liver metastasis)   1.3       BxPC-3- Pancreatic adenocarcinoma   0.0       HP AC- Pancreatic adenocarcinoma   0.0       MIA PaCa-2- Pancreatic carcinoma   0.0       CFPAC-1- Pancreatic ductal adenocarcinoma   1.6       PANC-1- Pancreatic epithelioid ductal carcinoma   0.0       T24- Bladder carcinma (transitional cell)   0.0       5637- Bladder carcinoma   0.0       HT-1197- Bladder carcinoma   0.0       UM-UC-3- Bladder carcinma (transitional cell)   0.0       A204- Rhabdomyosarcoma   0.0       HT-1080- Fibrosarcoma   0.0       MG-63- Osteosarcoma   0.0       SK-LMS-1- Leiomyosarcoma (vulva)   0.0       SJRH30- Rhabdomyosarcoma (met to bone marrow)   0.0       A431- Epidermoid carcinoma   0.0       WM266-4- Melanoma   0.0       DU 145- Prostate carcinoma (brain metastasis)   0.0       MDA-MB-468- Breast adenocarcinoma   0.0       SCC-4- Squamous cell carcinoma of tongue   0.0       SCC-9- Squamous cell carcinoma of tongue   0.0       SCO 15- Squamous cell carcinoma of tongue   0.0       CAL 27- Squamous cell carcinoma of tongue   0.0                    
     [0858]               TABLE UF                          Panel 4D                         Rel. Exp. (%)           Ag2893, Run       Tissue Name   159633002                             Secondary Th1 act   0.0       Secondary Th2 act   0.0       Secondary Tr1 act   0.0       Secondary Th1 rest   0.0       Secondary Th2 rest   1.2       Secondary Tr1 rest   0.0       Primary Th1 act   0.0       Primary Th2 act   0.0       Primary Tr1 act   0.0       Primary Th1 rest   0.0       Primary Th2 rest   0.7       Primary Tr1 rest   0.0       CD45RA CD4 lymphocyte act   0.0       CD45RO CD4 lymphocyte act   0.3       CD8 lymphocyte act   0.0       Secondary CD8 lymphocyte rest   0.2       Secondary CD8 lymphocyte act   0.0       CD4 lymphocyte none   0.0       2ry Th1/Th2/Tr1_anti-CD95 CH11   0.8       LAK cells rest   1.0       LAK cells IL-2   0.0       LAK cells IL-2 + IL-12   0.4       LAK cells IL-2 + IFN gamma   0.0       LAK cells IL-2 + IL-18   0.0       LAK cells PMA/ionomycin   0.0       NK Cells IL-2 rest   0.0       Two Way MLR 3 day   0.0       Two Way MLR 5 day   0.0       Two Way MLR 7 day   0.0       PBMC rest   0.3       PBMC PWM   0.4       PBMC PHA-L   0.0       Ramos (B cell) none   0.0       Ramos (B cell) ionomycin   0.0       B lymphocytes PWM   0.8       B lymphocytes CD40L and IL-4   0.6       EOL-1 dbcAMP   0.0       EOL-1 dbcAMP PMA/ionomycin   0.0       Dendritic cells none   0.0       Dendritic cells LPS   0.0       Dendritic cells anti-CD40   0.0       Monocytes rest   0.0       Monocytes LPS   0.0       Macrophages rest   0.0       Macrophages LPS   0.0       HUVEC none   0.0       HUVEC starved   0.0       HUVEC IL-1beta   0.0       HUVEC IFN gamma   0.0       HUVEC TNF alpha + IFN gamma   0.0       HUVEC TNF alpha + IL4   0.0       HUVEC IL-11   0.0       Lung Microvascular EC none   0.0       Lung Microvascular EC TNFalpha + IL-1beta   0.0       Microvascular Dermal EC none   0.0       Microsvasular Dermal EC TNFalpha + IL-1beta   0.0       Bronchial epithelium TNFalpha + IL1beta   0.0       Small airway epithelium none   1.7       Small airway epithelium TNFalpha + IL-1beta   3.0       Coronery artery SMC rest   0.0       Coronery artery SMC TNFalpha + IL-1beta   0.0       Astrocytes rest   4.4       Astrocytes TNFalpha + IL-1beta   5.8       KU-812 (Basophil) rest   0.0       KU-812 (Basophil) PMA/ionomycin   0.0       CCD1106 (Keratinocytes) none   0.0       CCD1106 (Keratinocytes) TNFalpha + IL-1beta   0.0       Liver cirrhosis   12.7       Lupus kidney   18.6       NCI-H292 none   6.5       NCI-H292 IL-4   5.6       NCI-H292 IL-9   6.8       NCI-H292 IL-13   3.6       NCI-H292 IFN gamma   2.9       HPAEC none   0.0       HPAEC TNF alpha + IL-1 beta   0.0       Lung fibroblast none   0.0       Lung fibroblast TNF alpha + IL-1 beta   0.0       Lung fibroblast IL-4   0.0       Lung fibroblast IL-9   0.0       Lung fibroblast IL-13   0.0       Lung fibroblast IFN gamma   0.0       Dermal fibroblast CCD1070 rest   0.7       Dermal fibroblast CCD1070 TNF alpha   0.0       Dermal fibroblast CCD1070 IL-1 beta   0.0       Dermal fibroblast IFN gamma   0.0       Dermal fibroblast IL-4   0.0       IBD Colitis 2   0.0       IBD Crohn&#39;s   1.2       Colon   0.8       Lung   34.2       Thymus   100.0       Kidney   0.0                    
     [0859] CNS_neurodegeneration_v1.0 Summary: Ag2893 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. Please see Panel 1.3D for discussion of this gene in the central nervous system.  
     [0860] Panel 1.3D Summary: Ag2893 Two experiments with the same probe and primer set produce results that are in excellent agreement, with highest expression of this gene in a renal cancer cell line (CTs=28-30). Significant expression is also seen in a cluster of renal cancer cell lines. 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 renal cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of renal cancer.  
     [0861] This gene is also expressed at low, but significant levels in the brain. Expression of this gene in the cerebral cortex suggests a role in CNS-specific processes. Homology to the tocopherol-associated protein (TAP) transcription factor suggests a role for this gene in tocopherol mediated gene transcription. Tocopherol is an essential vitamin involved in many CNS processes that may be mediated by both its antioxidant properties and ability to regulate gene transcription via this gene. Genetic disruption of tocopherol processing results in tocopherol deficiency and CNS disorders such as ataxia and neurodegeneration. Agents that modulate this gene or its protein product may thus be useful in the treatment of ataxia and neurodegenerative diseases.  
     [0862] See Yamauchi J, Iwamoto T, Kida S, Masushige S, Yamada K, Esashi T. Tocopherol-associated protein is a ligand-dependent transcriptional activator. Biochem Biophys Res Commun Jul. 13, 2001;285(2):295-9; and Yokota T, Igarashi K, Uchihara T, Jishage K, Tomita H, Inaba A, Li Y, Arita M, Suzuki H, Mizusawa H, Arai H. Delayed-onset ataxia in mice lacking alpha-tocopherol transfer protein: model for neuronal degeneration caused by chronic oxidative stress. Proc Natl Acad Sci USA 2001 Dec 18;98(26):15185-90.  
     [0863] Panel 2D Summary: Ag2893 Highest expression of this gene is seen in a sample derived from a kidney cancer cell line (CT=29.5). In addition, this sample is more highly expressed in kidney cancer than in adjacent normal 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.  
     [0864] Panel 3D Summary: Ag2893 Expression of this gene is detected primarily in samples derived from kidney cancer cell lines(CTs=30). 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 kidney cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of kidney cancer.  
     [0865] Panel 4D Summary: Ag2893 This gene is expressed at low but significant levels in the lung and thymus and in lupus kidney and cirrhotic liver. Thus, the transcript or the protein it encodes could be used for detection of these tissues. The expression of this gene suggests that the protein encoded by this transcript may play an important role in the normal homeostasis of the thymus and lung tissues. Therefore, therapeutics designed with the protein encoded by this transcript could be important for modulating T cell development in the thymus and for maintaining or restoring normal function to these lung during inflammation due to diseases such as asthma and emphysema. Additionally, induction of this transcript in other tissues such as the kidney and liver may be detrimental and antagonistic therapies designed with the protein encoded for by this transcript could be important in the treatment of diseases of these tissues.  
     Example D  
     Identification of Single Nucleotide Polymorphisms in NOVX nucleic Acid Sequences  
     [0866] 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.  
     [0867] SeCalling 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.  
     [0868] 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.  
     [0869] 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).  
     [0870] 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.  
     [0871] NOV2b SNP Data (CG112559-02)  
     [0872] Two polymorphic variants of NOV2b have been identified and are shown in Table SNP1.  
               TABLE SNP1                          Variants of NOV2b.                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified               13381923   285   C   T   0               c110.5085   475   A   T   0                  
 
     [0873] NOV3b SNP Data (CG115757-02)  
     [0874] One polymorphic variant of NOV3b has been identified and is shown in Table SNP2.  
               TABLE SNP2                          Variant of NOV3b.                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified               c110.6682   414   C   A   134   Ser   Tyr                  
 
     [0875] NOV7a SNP Data (CG134632-01)  
     [0876] One polymorphic variant of NOV7a has been identified and is shown in Table SNP3.  
               TABLE SNP3                          Variant of NOV7a.                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified               13378877   699   C   G   96   Pro   Pro                  
 
     [0877] NOV8a SNP Data (CG148411-01)  
     [0878] Four polymorphic variants of NOV8a have been identified and are shown in Table SNP4.  
               TABLE SNP4                          Variants of NOV8a                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13381925   180   G   A   0               13381926   429   C   T   78   Pro   Leu       13381915   435   G   A   80   Gly   Glu       13381924   752   A   G   0                  
 
     [0879] NOV19b SNP Data (CG54092-01)  
     [0880] Three polymorphic variants of NOV19b have been identified and are shown in Table SNP5.  
               TABLE SNP5                          Variants of NOV19b                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13376993   284   A   G   95   Glu   Gly       13376994   958   G   A   320   Ala   Thr       13376995   968   T   C   323   Leu   Pro                  
 
     [0881] NOV22c SNP Data (CG56618-04)  
     [0882] Eight polymorphic variants of NOV22c have been identified and are shown in Table SNP6.  
               TABLE SNP6                          Variants of NOV22c                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13381966   158   C   T   22   Ala   Val       13381967   258   C   T   55   Arg   Arg       13381979   282   G   A   63   Ser   Ser       13381980   285   G   A   64   Lys   Lys       13381968   338   G   A   82   Arg   His       13381981   360   A   G   89   Thr   Thr       13381982   362   G   A   90   Gly   Asp       13381969   834   A   G   247   Lys   Lys                  
 
     [0883] NOV24a SNP Data (CG59522-02)  
     [0884] Eight polymorphic variants of NOV22c have been identified and are shown in Table SNP7.  
               TABLE SNP7                          Variants of NOV24a                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13377472   285   T   C   91   Tyr   His       13380146   375   G   T   121   Ala   Ser       13377473   553   G   A   180   Arg   His       13377474   554   C   T   180   Arg   Arg       13381928   1262   T   C   416   Asn   Asn       13377475   2596   G   A   861   Arg   Gln                  
 
     Example E  
     Method of Use  
     Example E1  
     Method of use for CG154077-01, NOV9a (Human Sulfonylurea Receptor 2A)  
     [0885] The present invention discloses novel associations of proteins and polypeptides and the nucleic acids that encode them with various diseases or pathologies. The proteins and related proteins that are similar to them, are encoded by a cDNA and/or by genomic DNA. The Sulfonylurea Receptor 2A (CG154077)-encoded protein and any variants, thereof, are suitable as diagnostic markers, targets for an antibody therapeutic and targets for small molecule drugs. As such the current invention embodies the use of recombinantly expressed and/or endogenously expressed protein in various screens to identify such therapeutic antibodies and/or therapeutic small molecules, particularly for use in the treatment of obesity or diabetes.  
     [0886] Obesity and Diabetes are major public health concerns in the developed and developing world. It is estimated that over half of the adult US population is overweight with a body mass index (BMI) greater than the upper limit of normal (25) where the BMI is defined as the weight (Kg)/[height (m)] 2 . A common consequence of being overweight is hyperlipidemia and the development of insulin resistance. This is followed by the development of hyperglycemia, a hallmark of Type II diabetes. Left untreated, the hyperglycemia leads to microvascular disease and end organ damage that includes retinopathy, renal disease, cardiac disease, peripheral neuropathy and peripheral vascular compromise. Currently, over 16 million adults in the US are affected by Type II diabetes and the condition has now become rampant among school-age children as a consequence of the epidemic of obesity in that age group.  
     [0887] Several cellular, animal and clinical studies were performed to elucidate the genetic contribution to the etiology and pathogenesis of these conditions in a variety of physiologic, pharmacologic or native states. These studies utilized the core technologies at CuraGen Corporation to look at differential gene expression, protein-protein interactions, large-scale sequencing of expressed genes and the association of genetic variations such as, but not limited to, single nucleotide polymorphisms (SNPs) or splice variants in and between biological samples from experimental and control groups. The goal of such studies is to identify potential avenues for therapeutic intervention in order to prevent, treat the consequences or cure the conditions of obesity and diabetes.  
     [0888] In order to treat diseases, pathologies and other abnormal states or conditions in which a mammalian organism has been diagnosed as being, or as being at risk for becoming, other than in a normal state or condition, it is important to identify new therapeutic agents. Such a procedure includes at least the steps of identifying a target component within an affected tissue or organ, and identifying a candidate therapeutic agent that modulates the functional attributes of the target. The target component may be any biological macromolecule implicated in the disease or pathology. Commonly the target is a polypeptide or protein with specific functional attributes. Other classes of macromolecule may be a nucleic acid, a polysaccharide, a lipid such as a complex lipid or a glycolipid; in addition a target may be a sub-cellular structure or extra-cellular structure that is comprised of more than one of these classes of macromolecule. Once such a target has been identified, it may be employed in a screening assay in order to identify favorable candidate therapeutic agents from among a large population of substances or compounds.  
     [0889] In many cases the objective of such screening assays is to identify small molecule candidates; this is commonly approached by the use of combinatorial methodologies to develop the population of substances to be tested. The implementation of high throughput screening methodologies is advantageous when working with large, combinatorial libraries of compounds.  
     [0890] It is an objective of this invention to provide at least one target biopolymer that is intended to serve as the macromolecular component in a screening assay for identifying candidate pharmaceutical agents.  
     [0891] It is another objective of the present invention to provide screening assays that positively identify candidate pharmaceutical agents from among a combinatorial library of low molecular weight substances or compounds.  
     [0892] It is still a further objective of this invention to employ the candidate pharmaceutical agents in any of a variety of in vitro, ex vivo and in vivo assays in order to identify pharmaceutical agents with advantageous therapeutic applications in the treatment of a disease, pathology, or abnormal state or condition in a mammal.  
     [0893] Sulfonylurea Receptor 2 (SUR2) is a member of the superfamily of ATP-binding cassette (ABC) transporters. It functions as a drug-binding regulatory subunit of the muscle specific ATP-sensitive potassium channel. Recent data showed that disruption of SUR2 leads to increased insulin stimulated glucose uptake in skeletal muscle. (Chutkow W A, Samuel V, Hansen P A, Pu J, Valdivia C R, Makielski J C, Burant C F. Disruption of Sur2-containing K(ATP) channels enhances insulin-stimulated glucose uptake in skeletal muscle. Proc. Natl. Acad. Sci. USA 2001. 98,11760-4. PMID: 11562480; Chutkow W A, Simon M C, Le Beau M M, Burant C F. Cloning, tissue expression, and chromosomal localization of SUR2, the putative drug-binding subunit of cardiac, skeletal muscle, and vascular KATP channels. Diabetes 1996. 45,1439-45. PMID: 8826984; Halseth A E, Bracy D P, Wasserman D H. Functional limitations to glucose uptake in muscles comprised of different fiber types. Am. J. Physiol. Endocrinol. Metab. 2001. 280, E994-9. PMID: 11350781; Shindo T, Yamada M, Isomoto S, Horio Y, Kurachi Y. SUR2 subtype (A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandil. Br. J. Pharmacol. 1998.124, 985-91. PMID: 9692785; Reimann F, Ashcroft F M, Gribble F M. Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes 2001.50, 2253-9. PMID: 11574406; Moreau C, Jacquet H, Prost A L, D&#39;hahan N, Vivaudou M. The molecular basis of the specificity of action of K(ATP) channel openers. EMBO J. 2000.19, 6644-51. PMID: 11118199).  
     [0894] The present invention is based on the identification of biological macromolecules differentially modulated in a pathologic state, disease, or an abnormal condition or state. Among the pathologies or diseases of present interest include metabolic diseases, including those related to endocrinologic disorders, cancers, various tumors and neoplasias, inflammatory disorders, central nervous system disorders, and similar abnormal conditions or states. Important metabolic disorders with which the biological macromolecules are associated include obesity and diabetes mellitus, especially obesity and Type II diabetes. It is believed that obesity predisposes a subject to Type II diabetes. In very significant embodiments of the present invention, the biological macromolecules implicated in these pathologies and conditions are proteins and polypeptides, and in such cases the present invention is related as well to the nucleic acids that encode them. Methods that may be employed to identify relevant biological macromolecules include any procedures that detect differential expression of nucleic acids encoding proteins and polypeptides associated with the disorder, as well as procedures that detect the respective proteins and polypeptides themselves. Significant methods that have been employed by the present inventors, include GeneCalling® technology and SeqCalling™ technology, disclosed respectively, in U.S. Pat. No. 5,871,697, and in U.S. Ser. No. 09/417,386, filed Oct. 13, 1999, each of which is incorporated herein by reference in its entirety. GeneCalling® is also described in Shimkets, et al., “Gene expression analysis by transcript profiling coupled to a gene database query” Nature Biotechnology 17:198-803 (1999).  
     [0895] The invention provides polypeptides and nucleotides encoded thereby that have been identified as having novel associations with a disease or pathology, or an abnormal state or condition, in a mammal. Included in the invention are nucleic acid sequences and their encoded polypeptides. The sequences are collectively referred to as “obesity and/or diabetes nucleic acids” or “obesity and/or diabetes polynucleotides” and the corresponding encoded polypeptide is referred to as an “obesity and/or diabetes polypeptide” or “obesity and/or diabetes protein”. For example, an obesity and/or diabetes nucleic acid according to the invention is a nucleic acid including an obesity and/or diabetes nucleic acid, and an obesity and/or diabetes polypeptide according to the invention is a polypeptide that includes the amino acid sequence of an obesity and/or diabetes polypeptide. Unless indicated otherwise, “obesity and/or diabetes” is meant to refer to any of the sequences having novel associations disclosed herein.  
     [0896] The present invention identifies a set of proteins and polypeptides, including naturally occurring polypeptides, precursor forms or proproteins, or mature forms of the polypeptides or proteins, which are implicated as targets for therapeutic agents in the treatment of various diseases, pathologies, abnormal states and conditions. A target may be employed in any of a variety of screening methodologies in order to identify candidate therapeutic agents which interact with the target and in so doing exert a desired or favorable effect. The candidate therapeutic agent is identified by screening a large collection of substances or compounds in an important embodiment of the invention. Such a collection may comprise a combinatorial library of substances or compounds in which, in at least one subset of substances or compounds, the individual members are related to each other by simple structural variations based on a particular canonical or basic chemical structure. The variations may include, by way of nonlimiting example, changes in length or identity of a basic framework of bonded atoms; changes in number, composition and disposition of ringed structures, bridge structures, alicyclic rings, and aromatic rings; and changes in pendent or substituents atoms or groups that are bonded at particular positions to the basic framework of bonded atoms or to the ringed structures, the bridge structures, the alicyclic structures, or the aromatic structures.  
     [0897] A polypeptide or protein described herein, and that serves as a target in the screening procedure, includes the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, e.g., the full-length gene product, encoded by the corresponding gene. The naturally occurring polypeptide also includes the polypeptide, precursor or proprotein encoded by an open reading frame described herein. A “mature” form of a polypeptide or protein arises as a result of one or more naturally occurring processing steps as they may occur within the cell, including a host cell. The processing steps occur as the gene product arises, e.g., via cleavage of the amino-terminal methionine residue encoded by the initiation codon of an open reading frame, 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. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an amino-terminal signal sequence from residue 1 to residue M is cleaved, includes the residues from residue M+1 to residue N remaining. A “mature” form of a polypeptide or protein may also arise from non-proteolytic post-translational modification. Such non-proteolytic processes include, e.g., glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or the combination of any of them.  
     [0898] Sulfonylurea receptor 2 (SUR2, CG154077-01) was found to be up-regulated in fast twitch versus slow twitch skeletal muscle in mice on a high fat diet and in hyperglycemic/diabetic mice. It is known that glucose uptake is reduced in fast twitch muscle as compared to slow twitch muscle. Inhibition of SUR2 would favor the slow twitch muscle phenotype, thus increasing glucose uptake and improving insulin sensitivity.  
     [0899] As used herein, “identical” residues correspond to those residues in a comparison between two sequences where the equivalent nucleotide base or amino acid residue in an alignment of two sequences is the same residue. Residues are alternatively described as “similar” or “positive” when the comparisons between two sequences in an alignment show that residues in an equivalent position in a comparison are either the same amino acid or a conserved amino acid as defined below.  
     [0900] As used herein, a “chemical composition” relates to a composition including at least one compound that is either synthesized or extracted from a natural source. A chemical compound may be the product of a defined synthetic procedure. Such a synthesized compound is understood herein to have defined properties in terms of molecular formula, molecular structure relating the association of bonded atoms to each other, physical properties such as electropherographic or spectroscopic characterizations, and the like. A compound extracted from a natural source is advantageously analyzed by chemical and physical methods in order to provide a representation of its defined properties, including its molecular formula, molecular structure relating the association of bonded atoms to each other, physical properties such as electropherographic or spectroscopic characterizations, and the like.  
     [0901] As used herein, a “candidate therapeutic agent” is a chemical compound that includes at least one substance shown to bind to a target biopolymer. In important embodiments of the invention, the target biopolymer is a protein or polypeptide, a nucleic acid, a polysaccharide or proteoglycan, or a lipid such as a complex lipid. The method of identifying compounds that bind to the target effectively eliminates compounds with little or no binding affinity, thereby increasing the potential that the identified chemical compound may have beneficial therapeutic applications. In cases where the “candidate therapeutic agent” is a mixture of more than one chemical compound, subsequent screening procedures may be carried out to identify the particular substance in the mixture that is the binding compound, and that is to be identified as a candidate therapeutic agent.  
     [0902] As used herein, a “pharmaceutical agent” is provided by screening a candidate therapeutic agent using models for a disease state or pathology in order to identify a candidate exerting a desired or beneficial therapeutic effect with relation to the disease or pathology. Such a candidate that successfully provides such an effect is termed a pharmaceutical agent herein. Nonlimiting examples of model systems that may be used in such screens include particular cell lines, cultured cells, tissue preparations, whole tissues, organ preparations, intact organs, and nonhuman mammals. Screens employing at least one system, and preferably more than one system, may be employed in order to identify a pharmaceutical agent. Any pharmaceutical agent so identified may be pursued in further investigation using human subjects.  
     [0903] Use of the human Sulfonylurea Receptor 2A Gene as a Diagnostic and/or Target for Small Molecule Drugs and Antibody Therapeutics.  
     [0904] The analysis of CG154077-01 by the following algorithms shows the gene product is a plasma membrane associated ABC transporter with characteristic functional protein domains.  
     [0905] Functional Homology: Query: CG154077-01  
     [0906] ptnr:SWISSPROT-ACC:060706 Sulfonylurea receptor 2-Homo sapiens (Human), 1549  
     [0907] aa.  
     [0908] Length=1549  
     [0909] Score=7961 (2802.4 bits), Expect=0.0, P=0.0  
     [0910] Identities=1549/1549 (100%), Positives =1549/1549 (100*)  
     [0911] The Protein Translation of CG154077-01 was Shown by BLAST Analysis to be Identical to the Sulfonylurea Receptor 2 Sequence 060706 in the SwissProt Database.  
     [0912] PSORT result: Query: CG154077-01  
     [0913] plasma membrane—Certainty=0.8000(Affirmative)&lt;succ&gt; 
     [0914] Golgi body—Certainty=0.4000(Affirmative)&lt;succ&gt; 
     [0915] endoplasmic reticulum (membrane)—Certainty=0.3000(Affirmative)&lt;succ&gt; 
     [0916] microbody (peroxisome)—Certainty=0.3000(Affirmative)&lt;succ&gt; 
     [0917] PSORT analysis predicts that CG154077-01 is localized at the plasma membrane.  
     [0918] Mouse Dietary—Induced Obesity Study (BP24.02)  
     [0919] The predominant cause for obesity in clinical populations is excess caloric intake. This so-called diet-induced obesity (DIO) is mimicked in animal models by feeding high fat diets of greater than 40% fat content. The DIO study was established to identify the gene expression changes contributing to the development and progression of diet-induced obesity. In addition, the study design seeks to identify the factors that lead to the ability of certain individuals to resist the effects of a high fat diet and thereby prevent obesity. The sample groups for the study were selected from C57BL/6J mice and had body weights +1 S.D. (sd1), +4 S.D. (sd4) and +7 S.D. of the chow-fed controls (below). In addition, the biochemical profile of the +7 S.D. mice revealed a further stratification of these animals into mice that retained a normal glycemic profile in spite of obesity (ngsd7) and mice that demonstrated hyperglycemia (hgsd7). Tissues examined included hypothalamus, brainstem, liver, retroperitoneal white adipose tissue (WAT), epididymal WAT, brown adipose tissue (BAT), gastrocnemius muscle (fast twitch skeletal muscle) and soleus muscle (slow twitch skeletal muscle). The differential gene expression profiles for these tissues should reveal genes and pathways that can be used as therapeutic targets for obesity.  
     [0920] Results of GeneCalling Study BP24.02  
     [0921] A gene fragment of the mouse Sulfonylurea Receptor 2A was found to be up-regulated by 2 fold in the gastrocnemius versus soleus skeletal muscle in mouse on high fat diet (sd1) using CuraGen&#39;s GeneCalling™ method of differential gene expression. It was also found to be up-regulated by 3 fold in the gastrocnemius versus soleus skeletal muscle in obese mouse with hyperglycemia (hgsd7). A differentially expressed mouse gene fragment migrating, at approximately 97 nucleotides in length (Table E1.-solid vertical line) was definitively identified as a component of the mouse Sulfonylurea Receptor 2A cDNA (in the graphs, the abscissa is measured in lengths of nucleotides and the ordinate is measured as signal response). The method of comparative PCR was used for conformation of the gene assessment. The electropherographic peaks corresponding to the gene fragment of the mouse Sulfonylurea Receptor 2A are ablated when a gene-specific primer (see below) competes with primers in the linker-adaptors during the PCR amplification. The peaks at 97 nt in length are ablated (dotted or dashed trace) in the sample from both the gestational diabetic and normal pregnant female.  
     [0922] The direct sequence of the 97 nucleotide-long gene fragment and the gene-specific primers used for competitive PCR are indicated on the cDNA sequence of the Sulfonylurea Receptor 2A and are shown below in bold. The gene-specific primers at the 5′ and 3′ ends of the fragment are in italics.  
     [0923] Competitive PCR Primer for the Mouse Sulfonylurea Receptor 2A (fragment from 3054 to 3150 of the above listed sequence SEQ ID NO: 37 for NOV9a, CG154077-01, band size: 97) is shown in Table E1. 
 
 
     [0924] A Pfam analysis of CG154077 identifies 4 significant domains in this protein.  
     [0925] Pfam domains:Query: CG154077-01  
     [0926] Scores for sequence family classification (score includes all domains):  
                                           Model                   E-value   N   Description   Score                                                ABC_tran   2   ABC transporter   292.5       5.2e−84       ABC_membrane   2   ABC transporter transmembrane   250.5       2.3e−71       region.       DUF55   1   Protein of unknown function DUF55   −45.2       8.9       Folate_carrier   1   Reduced folate carrier   −215.2       7.9                  
 
     [0927] Parsed for domains:  
                                                           Model   Domain   seq-f   seq-t   hmm-f   hmm-t   score   E-value                                                                ABC_membrane   1/2   297    585 . . .   1   285 [ ]   122.5   7.8e−33       ABC_tran   1/2   698    888 . . .   1   198 [ ]   159.8   4.7e−44       ABC_membrane   2/2   994   1266 . . .   1   285 [ ]   136.3   5.6e−37       Folate_carrier   1/1   935   1282 . . .   1   416 [ ]   −215.2   7.9       DUF55   1/1   1304   1422 . . .   1   140 [ ]   −45.2   8.9       ABC_tran   2/2   1339   1522 . . .   1   198 [ ]   132.9   5.9e−36                  
 
     [0928] The E values for ABC transporter domains from the Pfam analysis of CG154077-01 are highly significant and indicate that it is an active ABC membrane transporter.  
     [0929] The analysis of CG154077-01 by the following algorithms shows the gene product is a plasma membrane associated ABC transporter with characteristic functional protein domains.  
     [0930] SeqCalling  
     [0931] Library:  
                                   Assembly   Tissue Expression                  129286786   Mammalian Tissue, Vein, Mammary gland/Breast,           Oviduct/Uterine Tube/Fallopian tube, Kidney       189213126   Mammalian Tissue, Heart, Vein, Brain, Mammary           gland/Breast, Oviduct/Uterine           Tube/Fallopian tube, Lung, Kidney, Skin       219115181   Mammalian Tissue, Heart, Vein, Lung, Kidney, Skin                  
 
     [0932] SeqCalling shows the expression of CG154077-01 in heart, brain, and several unrelated tissues.  
     [0933] The variants of the human Sulfonylurea Receptor 2A were obtained from direct cloning and/or public databases. In addition to the human version of the gene identified as being differentially expressed in the experimental study, other variants have been identified by direct sequencing of cDNAs derived from many different human tissues and from sequences in public databases.  
     [0934] There are at least three alternative spliced isoforms identified in human (SUR2A, SUR2Adelta, SUR2B). SUR2A delta is identical to SUR2A (CG154077-01), but lacks exon 14. SUR2B has a unique C-terminus from SUR2A originated from different exon usage (SUR2A use exon 39, SUR2B-exon 40).  
     [0935] RTQPCR Analysis  
     [0936] Panel 1.5 shows CG154077 is expressed in a number of metabolic tissues including adipose, kidney, heart, and pancreas, the highest level of expression of SUR2 in skeletal muscle.  
     [0937] Panel 5I shows CG154077 is expressed in human adipose and skeletal muscle. The expression level of CG154077 is significantly elevated in diabetic adipose/skeletal muscle (patient 12) compared to non-diabetic individuals. These data further support that up-regulation of human Sulfonylurea receptor A2 has pathogenic consequences, and inhibition of this gene or the activity of the protein encoded by this gene is beneficial for the treatment of diabetes.  
     [0938] Biochemistry, Cell Line Expression and Screening Assay Formulation  
     [0939] Sulfonylurea Receptor 2A (SUR2) is a regulatory subunit of potassium channel. Usual way to assay the activity of the channel is to measure the current by path-clamp method in transfected mammalian cell line or in Xenopus Oocytes expressed recombinant protein. There are known activators, for example clinical vaso-relaxant agent (penacidil). It has been shown that sulfoneurea compound is able to inhibit SUR2, but from 100 to 1000 less effective than For SUR1.  
     [0940] Cell lines expressing the Sulfonylurea Receptor 2A can be obtained from the RTQ-PCR results shown above. These and other Sulfonylurea Receptor 2A expressing cell lines could be used for screening purposes.  
     [0941] While not to be limited by theory, the inventor proposes that disruption of Sulfonylurea Receptor 2 contaning potassium channels enhances insulin-stimulated glucose uptake in skeletal muscle and that Sulfonylurea Receptor 2 is up-regulated in fast twitch muscle versus slow twitch in the animal model on a high fat diet and in the animal model with hyperglycemia. It is known that glucose uptake is reduced in fast twitch muscle compared to slow twitch. Therefore inhibition of Sulfonylurea Receptor 2 would increase insulin stimulate glucose uptake and favor slow twitch muscle phenotype, thus improving insulin sensitivity. An inhibitor/antagonist of the human Sulfonylurea Receptor 2A would be beneficial in the treatment of diabetes.  
     Example E2  
     Human Protein Kinase MEK2-like Proteins, Nucleic Acids Encoding the Same &amp; Methods of Use Thereof  
     [0942] In order to treat diseases, pathologies and other abnormal states or conditions in which a mammalian organism has been diagnosed as being, or as being at risk for becoming, other than in a normal state or condition, it is important to identify new therapeutic agents.  
     [0943] MEK2 is a dual specificity protein kinase involved in MAPK/ERK signaling cascade (Lewis T S, Shapiro P S, Ahn N G., 1998, Signal transduction through MAP kinase cascades. Adv Cancer Res;74:49-139; PMID: 9561267). The cascade is activated by a wide variety of receptors involved in growth and differentiation including receptor tyrosine kinases, integrins, and ion channels. The specific components of the cascade vary greatly among different stimuli, but the architecture of the pathway usually includes a set of adaptors linking the receptor to a guanine nucleotide exchange factor transducing the signal to small GTP binding proteins (Ras, Rap 1), which in turn activate the core unit of the cascade composed of a MAPKKK (Raf), a MAPKK (MEK1/2) and MAPK (ERK). An activated ERK dimer can regulate targets in the cytosol and also translocate to the nucleus where it phosphorylates a variety of transcription factors regulating gene expression.  
     [0944] MEK1 and MEK2 belong to the MAP kinase kinase family and directly contribute to ERK activation that acts as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. It is known that both MEKs are activated in response to TNF alpha treatment (Jain R G, Phelps K D, Pekala P H.,1999) Tumor necrosis factor-alpha initiates signal transduction in 3T3-L1 adipocytes (J Cell Physiol. 179: 58-66; PMID: 10082133; Zhang H H, Halbleib M, Ahmad F, Manganiello V C, Greenberg A S). Tumor necrosis factor-alpha stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP (Diabetes 51(10): 2929-35; 2002; PMID: 12351429). Recently it has been shown that treating adipocytes with an antagonist of both MEKs restores insulin sensitivity (Engelman J A, Berg A H, Lewis R Y, Lisanti M P, Scherer P E. (2000) Tumor necrosis factor alpha-mediated insulin resistance, but not dedifferentiation, is abrogated by MEK1/2 inhibitors in 3T3-LI adipocytes. Mol. Endocrinology 14, 1557; PMID: 11043572).  
     [0945] Several cellular, animal and clinical studies were performed to elucidate the genetic contribution to the etiology and pathogenesis of these conditions in a variety of physiologic, pharmacologic or native states. These studies utilized the core technologies at CuraGen Corporation to look at differential gene expression, protein-protein interactions, large-scale sequencing of expressed genes and the association of genetic variations such as, but not limited to, single nucleotide polymorphisms (SNPs) or splice variants in and between biological samples from experimental and control groups. The goal of such studies is to identify potential avenues for therapeutic intervention in order to prevent, treat the consequences or cure the conditions of obesity and diabetes.  
     [0946] The present invention discloses novel associations of proteins and polypeptides and the nucleic acids that encode them with various diseases or pathologies. The proteins and related proteins that are similar to them, are encoded by a cDNA and/or by genomic DNA. The proteins, polypeptides and their cognate nucleic acids were identified by the inventor in certain cases. In particular, the Protein Kinase MEK2 protein encoded by CG55838-02 and any variants, thereof, are suitable as diagnostic markers, targets for an antibody therapeutic and targets for small molecule drugs. The inventor has discovered that expression of Protein Kinase MEK2 is down-regulated in skeletal muscle in mice resistant to diet-induced obesity indicating that specific inhibition of MEK2 will favor the lean phenotype. The inventor also found that Protein Kinase MEK2 is dysregulated in genetically obese mice. The inventor has further disclosed that Protein Kinase MEK2 is elevated in liver in obese patients. Taken together, these findings indicate that MEK2 is a positive marker for obesity in insulin-responsive tissues. The inventor proposes that MEK2 is a mediator of insulin resistance associated with obesity and therefore, an antagonist of MEK2 should be beneficial for the treatment of diabetes and/or obesity. A preferred method of the invention is the use of the Protein Kinase MEK2 for identifying an agonist that would be beneficial in the treatment of obesity and/or diabetes. As such, the current invention embodies the use of recombinantly expressed and/or endogenously expressed protein in various screens to identify such therapeutic antibodies and/or therapeutic small molecules.  
     [0947] The present invention is based on the identification of biological macromolecules differentially modulated in a pathologic state, disease, or an abnormal condition or state. Among the pathologies or diseases of present interest include metabolic diseases, including those related to endocrinologic disorders, cancers, various tumors and neoplasias, inflammatory disorders, central nervous system disorders, and similar abnormal conditions or states. Important metabolic disorders with which the biological macromolecules are associated include obesity and diabetes mellitus, especially obesity and Type II diabetes. It is believed that obesity predisposes a subject to Type II diabetes. In very significant embodiments of the present invention, the biological macromolecules implicated in these pathologies and conditions are proteins and polypeptides, and in such cases the present invention is related as well to the nucleic acids that encode them. Methods that may be employed to identify relevant biological macromolecules include any procedures that detect differential expression of nucleic acids encoding proteins and polypeptides associated with the disorder, as well as procedures that detect the respective proteins and polypeptides themselves. Significant methods that have been employed by the present inventors, include GeneCalling 0 technology and SeqCalling™ technology, disclosed respectively, in U.S. Pat. No. 5,871,697, and in U.S. Ser. No. 09/417,386, filed Oct. 13, 1999, each of which is incorporated herein by reference in its entirety. GeneCalling C is also described in Shimkets, et al., “Gene expression analysis by transcript profiling coupled to a gene database query” Nature Biotechnology 17:198-803 (1999).  
     [0948] The invention provides polypeptides and nucleotides encoded thereby that have been identified as having novel associations with a disease or pathology, or an abnormal state or condition, in a mammal. Included in the invention are nucleic acid sequences and their encoded polypeptides. The sequences are collectively referred to as “obesity and/or diabetes nucleic acids” or “obesity and/or diabetes polynucleotides” and the corresponding encoded polypeptide is referred to as an “obesity and/or diabetes polypeptide” or “obesity and/or diabetes protein”. For example, an obesity and/or diabetes nucleic acid according to the invention is a nucleic acid including an obesity and/or diabetes nucleic acid, and an obesity and/or diabetes polypeptide according to the invention is a polypeptide that includes the amino acid sequence of an obesity and/or diabetes polypeptide. Unless indicated otherwise, “obesity and/or diabetes” is meant to refer to any of the sequences having novel associations disclosed herein.  
     [0949] The present invention identifies a set of proteins and polypeptides, including naturally occurring polypeptides, precursor forms or proproteins, or mature forms of the polypeptides or proteins, which are implicated as targets for therapeutic agents in the treatment of various diseases, pathologies, abnormal states and conditions. A target may be employed in any of a variety of screening methodologies in order to identify candidate therapeutic agents which interact with the target and in so doing exert a desired or favorable effect. The candidate therapeutic agent is identified by screening a large collection of substances or compounds in an important embodiment of the invention. Such a collection may comprise a combinatorial library of substances or compounds in which, in at least one subset of substances or compounds, the individual members are related to each other by simple structural variations based on a particular canonical or basic chemical structure. The variations may include, by way of nonlimiting example, changes in length or identity of a basic framework of bonded atoms; changes in number, composition and disposition of ringed structures, bridge structures, alicyclic rings, and aromatic rings; and changes in pendent or substituents atoms or groups that are bonded at particular positions to the basic framework of bonded atoms or to the ringed structures, the bridge structures, the alicyclic structures, or the aromatic structures.  
     [0950] A polypeptide or protein described herein, and that serves as a target in the screening procedure, includes the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, e.g., the full-length gene product, encoded by the corresponding gene. The naturally occurring polypeptide also includes the polypeptide, precursor or proprotein encoded by an open reading frame described herein. A “mature” form of a polypeptide or protein arises as a result of one or more naturally occurring processing steps as they may occur within the cell, including a host cell. The processing steps occur as the gene product arises, e.g., via cleavage of the amino-terminal methionine residue encoded by the initiation codon of an open reading frame, 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. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an amino-terminal signal sequence from residue 1 to residue M is cleaved, includes the residues from residue M+1 to residue N remaining. A “mature” form of a polypeptide or protein may also arise from non-proteolytic post-translational modification. Such non-proteolytic processes include, e.g., glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or the combination of any of them.  
     [0951] As used herein, “identical” residues correspond to those residues in a comparison between two sequences where the equivalent nucleotide base or amino acid residue in an alignment of two sequences is the same residue. Residues are alternatively described as “similar” or “positive” when the comparisons between two sequences in an alignment show that residues in an equivalent position in a comparison are either the same amino acid or a conserved amino acid as defined below.  
     [0952] As used herein, a “chemical composition” relates to a composition including at least one compound that is either synthesized or extracted from a natural source. A chemical compound may be the product of a defined synthetic procedure. Such a synthesized compound is understood herein to have defined properties in terms of molecular formula, molecular structure relating the association of bonded atoms to each other, physical properties such as electropherographic or spectroscopic characterizations, and the like. A compound extracted from a natural source is advantageously analyzed by chemical and physical methods in order to provide a representation of its defined properties, including its molecular formula, molecular structure relating the association of bonded atoms to each other, physical properties such as electropherographic or spectroscopic characterizations, and the like.  
     [0953] As used herein, a “candidate therapeutic agent” is a chemical compound that includes at least one substance shown to bind to a target biopolymer. In important embodiments of the invention, the target biopolymer is a protein or polypeptide, a nucleic acid, a polysaccharide or proteoglycan, or a lipid such as a complex lipid. The method of identifying compounds that bind to the target effectively eliminates compounds with little or no binding affinity, thereby increasing the potential that the identified chemical compound may have beneficial therapeutic applications. In cases where the “candidate therapeutic agent” is a mixture of more than one chemical compound, subsequent screening procedures may be carried out to identify the particular substance in the mixture that is the binding compound, and that is to be identified as a candidate therapeutic agent.  
     [0954] As used herein, a “pharmaceutical agent” is provided by screening a candidate therapeutic agent using models for a disease state or pathology in order to identify a candidate exerting a desired or beneficial therapeutic effect with relation to the disease or pathology. Such a candidate that successfully provides such an effect is termed a pharmaceutical agent herein. Nonlimiting examples of model systems that may be used in such screens include particular cell lines, cultured cells, tissue preparations, whole tissues, organ preparations, intact organs, and nonhuman mammals. Screens employing at least one system, and preferably more than one system, may be employed in order to identify a pharmaceutical agent. Any pharmaceutical agent so identified may be pursued in further investigation using human subjects.  
     [0955] In particular the invention relates to the use of Protein Kinase MEK2 protein as a diagnostic and/or target for small molecule drugs and antibody therapeutics.  
     [0956] The inventor has discovered that Protein Kinase MEK2 is down-regulated in skeletal muscle in mice resistant to diet-induced obesity indicating that inhibition of MEK2 will favor the lean phenotype. The inventor also found that Protein Kinase MEK2 is dysregulated in genetically obese mice. The inventor has further disclosed that Protein Kinase MEK2 is elevated in liver in obese patients. Taken together, these findings show that MEK2 is a positive marker for obesity in insulin-responsive tissues. The inventor shows that MEK2 is the most abundant isoform expressed in skeletal muscle and liver, two major insulin sensitive tissues. Not to be limited by a particular mechanism of action, the inventor nevertheless proposes that MEK2 is a mediator of insulin resistance and/or diabetes associated with obesity. In a particular embodiment of the invention, Protein Kinase MEK2 is a target for screening. As such, the current invention embodies the use of recombinantly expressed and/or endogenously expressed protein in various screens to identify Protein Kinase MEK2 antagonist, therapeutic antibodies and/or therapeutic small molecules beneficial in the treatment of obesity and/or diabetes.  
     [0957] Results from GeneCallin® Experiments  
     [0958] Materials and Methods  
     [0959] The following sections describe the study design(s) used to identify the PROTEIN KINASE MEK2-encoded protein and any variants, thereof, as being suitable as diagnostic markers, targets for an antibody therapeutic and targets for a small molecule drugs for Obesity and Diabetes.  
     [0960] Mouse Dietary—Induced Obesity Study (BP24.02)  
     [0961] The predominant cause for obesity in clinical populations is excess caloric intake. This so-called diet-induced obesity (DIO) is mimicked in animal models by feeding high fat diets of greater than 40% fat content. The mouse DIO study was established to identify the gene expression changes contributing to the development and progression of diet-induced obesity. In addition, the study design seeks to identify the factors that lead to the ability of certain individuals to resist the effects of a high fat diet and thereby prevent obesity. The sample groups for the study were selected from C57BL/6J mice and had body weights +1 S.D. (sd1), +4 S.D. (sd4) and +7 S.D. of the chow-fed controls (below). In addition, the biochemical profile of the +7 S.D. mice revealed a further stratification of these animals into mice that retained a normal glycemic profile in spite of obesity (ngsd7) and mice that demonstrated hyperglycemia (hgsd7). Tissues examined included hypothalamus, brainstem, liver, retroperitoneal white adipose tissue (WAT), epididymal WAT, brown adipose tissue (BAT), gastrocnemius muscle (fast twitch skeletal muscle) and soleus muscle (slow twitch skeletal muscle). Differential gene expression profiles for these tissues should reveal genes and pathways that can be used as therapeutic targets for obesity.  
     [0962] Mouse Obesity Study (MB.04)  
     [0963] A large number of mouse strains have been identified that differ in body mass and composition. The AKR and NZB strains are obese, the SWR, C57L and C57BL/6 strains are of average weight whereas the SM/J and Cast/Ei strains are lean. Understanding the gene expression differences in the major metabolic tissues from these strains will elucidate the pathophysiologic basis for obesity. These specific strains of rat were chosen for differential gene expression analysis because quantitative trait loci (QTL) for body weight and related traits had been reported in published genetic studies. Tissues included whole brain, skeletal muscle, visceral adipose, and liver.  
     [0964] Results of Mouse Dietary—Induced Obesity Study (BP24.02)  
     [0965] A fragment of the mouse Protein Kinase MEK2 gene (fragment from 249 to 301; band size: 53 nt) was initially found to be down-regulated by 1.6 fold in the gastrocnemius (glycolytic) skeletal muscle relative to soleus (oxidative) skeletal muscle of diet induced obesity-resistant (sd1) mice using CuraGen&#39;s GeneCalling™ method of differential gene expression. A differentially expressed mouse gene fragment migrating at approximately 51.7 nucleotides in length (Table E2-solid vertical line) was definitively identified as a component of the mouse Protein Kinase MEK2 cDNA (in the graphs, the abscissa is measured in lengths of nucleotides and the ordinate is measured as signal response). The method of competitive PCR using a gene-specific primer was used for confirmation of the gene assessment. The electrophoretic peak corresponding to the gene fragment of the mouse Protein Kinase MEK2 is ablated when a nested, gene-specific primer (see Table E2) competes with the primer sequences in the linker-adaptors of the dyrsegulated gene fragment during the PCR amplification. The peak at 51.7 nt in length is ablated (dotted or dashed trace) in the sample from soleus (oxidative) skeletal muscle of obesity-resistant (sd1) mice (see Table E2) In conclusion, MEK2 down-regulation observed in sd1 mice suggest that inhibition of Protein Kinase MEK2 would promote favorable obesity-resistant condition and supports the hypothesis that an antagonist of MEK2 would be beneficial for the treatment of obesity and/or diabetes. 
 
 
     [0966] Results of Mouse Obesity Study (MB.04)  
     [0967] A fragment of the mouse Protein Kinase MEK2 gene (fragment from 1169 to 1304; band size 136 nt) was initially found to be down-regulated by 1.7 fold in the skeletal muscle of normal C57L/J mice relative to genetically lean Cast/Ei mice using CuraGen&#39;s GeneCalling™ method of differential gene expression. The same fragment was up-regulated by 2.6 fold in skeletal muscle of normal SWR1 mice compared genetically lean Cast/Ei mice. A differentially expressed mouse gene fragment migrating, at approximately 137 nucleotides in length (Table E3. solid vertical line) was definitively identified as a component of the mouse Protein Kinase MEK2 cDNA (in the graphs, the abscissa is measured in lengths of nucleotides and the ordinate is measured as signal response). The method of competitive PCR was used for confirmation of the gene assessment. The electrophoretic peak corresponding to the gene fragment of the mouse Protein Kinase MEK2 is ablated when a gene-specific primer (see Table E3) competes with primers in the linker-adaptors during the PCR amplification. The peak at 136 nt in length is ablated (dotted or dashed trace) in the sample from the Cast/Ei mice (see Table E3). The finding that MEK2 is dysregulated in the animals with different weights is suggestive of the role of MEK2 in disease condition associated with obesity. 
 
 
     [0968] Human CG55838-02 Sequence Identification  
     [0969] Materials and Methods  
     [0970] SeqCalling fragments were identified by the CuraTools™ program, SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed. Such sequences were included in the derivation of Acc. No. CG55838-02 only when the extent of identity in the overlap region with one or more SeqCalling assemblies was high. The extent of identity may be, for example, about 90% or higher, preferably about 95% or higher, and even more preferably close to or equal to 100%. When necessary, the process to identify and analyze SeqCalling fragments and genomic clones was reiterated to derive the full-length sequence. 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. Public proteins used for in-silico prediction were thus included in the invention: The full length sequence of the protein of invention CG55838-02 was predicted using Curatools™ program, GeneAngler.  
     [0971] A Pfam analysis of CG55838-02 identifies a protein kinase domain in this protein. The E values corresponding to this domain (4e-72) is highly significant and indicates that the protein encoded by this gene has a catalytically active domain characteristic of members of the Protein Kinase MEK2 protein family. The human Protein Kinase MEK2 is 400 amino acids in length, maps to human chromosome 7q32, and is located in the cytoplasm.  
     [0972] Human Protein Kinase MEK2Gene Variants and SNPs  
     [0973] One splice-form variant has been identified. This novel isoform contains a deletion in the kinase domain and preserves the ATP and phosphorylation sites. Several amino acid-changing and non-amino acid-changing cSNPs were identified at CuraGen and are shown in Table E1 below, where UCP=uncharged polar, NP=non polar, A=acidic, and B=basic. Those cSNPs with ID “cgsp” refer to CuraGen proprietary SNPs, whereas those labeled “hsnp” are from public databases. The preferred variant of all those identified, to be used for screening purposes, is CG55838-02.  
               TABLE E4                          CG55838-02 SNPs                                                         SNP                           SNP       MATCH           MATCH       POSITION           AA           POSITION       ON   ORIG   NEW   CHANGE       SNP ID   ON DNA   ALLELES   PROTEIN   AA   AA   TYPE   STRAND               cgsp:13375615   471   G/A   151   Asp   Asp   Silent   −       cgsp:cg34b.118   548   A/C   177   Val   Gly   NP to   −                               UCP       cgsp:13379307   678   C/A   220   Ile   Ile   Silent   +                  
 
     [0974] Expression Profile of the Human Protein Kinase MEK2Gene (CG55838-02) (Described Above in the RTQPCR Section for CG55838-02).  
     [0975] Gene Expression Analysis Using CuraChip  
     [0976] CuraGen has developed a gene microarray (CuraChip 1.2) for the identification of biologically important markes or disease or pathologicstates and targets for therapeutic intervention. It provides a high-throughput means of global mRNA expression analyses of CuraGen&#39;s collection of cDNA sequences representing the Pharmaceutically Tractable Genome (PTG). This sequence set includes genes which can be developed into protein therapeutics, or used to develop antibody or small molecule therapeutics. CuraChip 1.2 contains almost 11,000 oligos representing approximately 8,500 gene loci, including (but not restricted to) kinases, ion channels, G-protein coupled receptors (GPCRs), nuclear hormone receptors, proteases, transporters, metabolic enzymes, hormones, growth factors, chemokines, cytokines, complement and coagulation factors, and cell surface receptors.  
     [0977] The CuraChip cDNAs were represented as 30-mer oligodeoxyribonucleotides (oligos) on a glass microchip. Hybridization methods using the longer CuraChip oligos are more specific compared to methods using 25-mer oligos. CuraChip oligos were synthesized with a linker, purified to remove truncated oligos (which can influence hybridization strength and specificity), and spotted on a glass slide. Oligo-dT primers were used to generate cRNA probes for hybridization from samples of interest. A biotin-avidin conjugation system was used to detect hybridized probes with a fluorophore-labeled secondary antibody. Gene expression was analyzed using clustering and correlation bioinformatics tools such as Spotfire® (Spotfire, Inc., 212 Elm Street, Somerville, Mass. 02144) and statistical tools such as multivariate analysis (MVA).  
     [0978] Analysis of Differential Gene Expression in Diabetes and Obesity Using CuraChip Analysis.  
     [0979] Gene expression profiles were generated from autopsy tissues collected for RNA extraction from 12 healthy and 12 diabetic male patients belonging to each of four ethnic groups, under the age 62, that spanned body-mass indexes (BMI) representing normal (20-25), overweight (25-30) and obese (&gt;30) phenotypes.  
     [0980] The metabolic tissues included psoas (skeletal muscle) and diaphragm (skeletal muscle), visceral adipose, subcutaneous adipose, small intestine, liver, pancreas and hypothalamus. Patient descriptions are as shown in Table E2:  
                                           TABLE E5                                                   A1C                                   last       Patient                           lab.       ID   AGE   BMI   SEX   DX   Ethnicity   Meds   Draw                  42-1   51   28   M   Diabetic   Cau   insulin   7.7       42-13   60   22   M   Diabetic   Cau   Micronase   7.6       42-17   61   23   M   Diabetic   African   Insulin,   7.8                           Am   Glucophage       42-2   52   29   M   Diabetic   Cau   insulin,   8.3                               Micronase       42-20   50   23   M   Diabetic   Asian   insulin   7.7       42-21   59   33   M   Diabetic   Hispanic   insulin   8.4       42-22   52   21   M   Diabetic   Hispanic   insulin   3.1       42-23   54   29   M   Diabetic   Hispanic   insulin   7.5       42-4   64   31   M   Diabetic   Cau   insulin,   7.9                               Micronase       42-6   45   31   M   Diabetic   African   insulin,   8.1                           Am   Micronase       42-8   47   30   M   Diabetic   African   insulin,   7.9                           Am   Micronase       42-9   39   31   M   Diabetic   Asian   insulin   5.5       42-25   41   31   M   Non-Diabetic   African   N/A   N/A                           Am       42-26   61   30   M   Non-Diabetic   Cau   N/A   N/A       42-28   50   22   M   Non-Diabetic   Asian   N/A   N/A       42-29   62   33   M   Non-Diabetic   Cau   N/A   N/A       42-31   51   31   M   Non-Diabetic   Hispanic   N/A   N/A       42-34   34   31   M   Non-Diabetic   Asian   N/A   N/A       42-35   52   28   M   Non-Diabetic   Hispanic   N/A   N/A       42-37   49   30   M   Non-Diabetic   African   N/A   N/A                           Am       42-39   63   24   M   Non-Diabetic   Cau   N/A   N/A       42-40   50   25   M   Non-Diabetic   Cau   N/A   N/A       42-41   54   21   M   Non-Diabetic   Hispanic   N/A   N/A                  
 
     [0981] Total RNA from each tissue was isolated and used to generate cRNA, which was labeled and hybridized to the proprietary microarray (CuraChip 1.2). Fluorescence intensities of scanned images were quantified and normalized.  
     [0982] The patients were grouped based on their disease status: Diabetic and Nondiabetic; or based on their BMIs: patients with low BMI (BMI is under 25), patients with medium BMI (BMI is above 25 and below 30) and patients with high BMI (BMI is above 30).  
     [0983] RTQ-PCR Analysis  
     [0984] Expression of gene Protein kinase MEK2, CG55838-02 was assessed using the primer-probe set Ag2022, described in Table PA. Results of the RTQ-PCR runs are shown in Tables PD, PE, PG and PH.  
     [0985] General_screening_panel v1.3 (MEK2) and 1.6 (MEK1) Summary: Protein Kinase MEK2 gene is a ubiquitously expressed gene with the highest level of expression in skeletal muscle (CT=27.4). High expression in one of the major insulin-responsive tissue is in agreement with the results from the GeneCalling study and strengthens the hypothesis that MEK2 contributes to the pathologic insulin-resistant condition in skeletal muscle. In contrast, MEK1 is not expressed in skeletal muscle, but shows ubiquitous expression in cancer tissues. Among the normal tissues, MEK1 shows high expression in brain. Taken together, the data show that MEK2 is the predominant gene expressed in skeletal muscle and liver, thus the preferred target for the treatment of insulin resistance in obesity and/or diabetes.  
     [0986] Panel 5 Islet Summary (MEK2): Panel 5I shows high expression of the Protein Kinase MEK2 gene in cultured adipocytes, kidney and skeletal muscle (CTs=28-29). Notably, MEK2 was significantly up-regulated in skeletal muscle from a gestational diabetic patient (Patient 12) compared to skeletal muscle of normal patients (Patients 11 and 9) that further strengthens the hypothesis that MEK2 contribute to diabetes and/or obesity.  
     [0987] CuraChip Results:  
     [0988] Expression of Protein kinase MEK2, CG55838-02 was assessed using an oligonucleotide specific for the MEK2 gene. The mean value with standard deviation of fluorescence intensity for Protein kinase MEK2 for each patient group was calculated: Diabetic patients, NonDiabetic patients, low BMI patients; medium BMI patients; high BMI patients.  
     [0989] No change has been detected in MEK2 expression in pancreas, visceral adipose and small intestine between the groups. The expression of Protein kinase MEK2 was elevated in skeletal muscle (psoas) upon an increase in BMI values, however the data were not statistically significant because of the insufficient number of patients in the group (data not shown). In liver the expression of Protein kinase MEK2 was drastically up-regulated in obese patients (FIG. E4). Notably, MEK2 up-regulation in obese liver was more profound in Diabetic patients compared to Nondiabetic patients, suggesting of the role of MEK2 in both obesity and diabetes. In conclusion, CuraChip analysis shows that MEK2 up-regulation positively correlates with obesity, insulin resistance and diabetes in human liver. The findings strengthen the hypothesis that inhibition of MEK2 may be beneficial for the treatment of obesity and/or diabetes. 
 
 
     [0990] Biochemistry/Cell Line Expression/Screening Assay Formulation  
     [0991] Assays for screening for antibody therapeutics or small molecule drugs targeting human Protein kinase MEK2 can be formulated utilizing the recombinant protein or endogenous MEK2 expressed in cell lines (non-exhaustive list of them from the RTQ-PCR results shown above).  
     [0992] To assay the serine/threonine kinase activity of Protein kinase MEK2 the phosphorylation reaction with generic/specific peptide substrate[s] and  32 P-ATP followed by the measurement of incorporation of radioactive phosphate into the substrate can be utilized. To assess full activity of Protein kinase MEK2, the active, phosphorylated form of MEK2 should be used in the screening; endogenously phosphorylated MEK2 can be obtained by immunoprecipitation from activated cells or by use of a constitutively active mutant of MEK2 (S222E/S226D) in the screen. To assure the selectivity of the compounds, endogenous substrates may be used such as recombinant ERK1/2. To evaluate the efficacy of the compound, several cellular assays can be used such as insulin-stimulated glucose up-take in insulin-responsive cells or insulin-stimulated lipolysis in adipocytes.  
     [0993] Physical cDNA Clone Available for Expression and Screening Purposes  
     [0994] Materials and Methods  
     [0995] Exon Linking: The cDNA coding for the CG55838-02 sequence was cloned by the polymerase chain reaction (PCR) using the primers designed based on known cDNA sequences or in silico predictions of the full length or some portion (one or more exons) of the cDNA/protein sequence of the invention. These primers were used to amplify a cDNA from a pool containing expressed human sequences derived from the following tissues: adrenal gland, bone marrow, brain-amygdala, brain-cerebellum, brain-hippocampus, brain-substantia nigra, brain-thalamus, brain-whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma-Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea and uterus.  
     [0996] Physical Clone: The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening purposes.  
     [0997] In Frame Cloning: In frame cloning is a process designed to insert DNA sequences into expression vectors such that the encoded proteins can be produced. The expressed proteins were either full length or corresponding to specific domains of interest. The PCR template was based on a previously identified plasmid (the PCR product derived by exon linking, covering the entire open reading frame) when available, or on human cDNA(s). The human cDNA pool was composed of 5 micrograms of each of the following human tissue cDNAs: adrenal gland, whole brain, amygdala, cerebellum, thalamus, bone marrow, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, liver, lymphoma, Burkitt&#39;s Raji cell line, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small Intestine, spleen, stomach, thyroid, trachea, uterus. For downstream cloning purposes, the forward and reverse primers included in-frame restriction sites. The amplified product was detected by agarose gel electrophoresis. The fragment was gel-purified and ligated into the pCR2.1 vector (Invitrogen, Carlsbad, Calif.) following the manufacturer&#39;s recommendation. Twenty four clones per transformation were picked and a quality control step was performed to verify that these clones contain an insert of the anticipated size. Subsequently, eight of these clones were sequenced, and assembled in a fashion similar to the SeqCalling process. In addition to analysis of the entire sequence assembly, sequence traces were evaluated manually.  
     [0998] The CG55838-02 gene described above, encoding the human Protein Kinase MEK2, represents a full-length physical clone and may be used directly for expression and screening purposes. Although the sequences are the preferred isoforms, any of the other isoforms may be used for similar purposes. Furthermore, under varying assay conditions may dictate which isoform may supplant the listed isoforms.  
     Example F  
     PathCalling Interaction  
     Example F1  
     Interactions of CG57509-02 in the Calpain-3 Pathway  
     [0999] Analysis of Novel Interactions in the Calpain 3 Pathway  
     [1000] The present invention discloses novel associations of proteins and polypeptides and the nucleic acids that encode them, as identified in a yeast-2-hybrid screen using a cDNA library or one-by-one matrix reactions. The proteins and related proteins that are similar to them are encoded by a cDNA and/or by genomic DNA and were identified in some cases by CuraGen Corporation.  
     [1001] In the current invention, protein interactions may include the interaction of a protein fragment with full-length protein, a protein fragment with another protein fragment, or full-length proteins with each other. The protein interactions disclosed in the present invention may also represent significant discoveries of functional importance to specific diseases or pathological conditions in which novel proteins are found to be components of known pathways, known proteins are found to be components of novel pathways, or novel proteins are found to be components of novel pathways.  
     [1002] The Calpain protein(s), and protein family(ies), its interactors and any variants, thereof, are suitable as targets for antibody therapeutics, protein drugs, and/or targets for small molecule drugs. As such, the presence of these complexes and pathways and their disregulation may be used as a marker or as a diagnostic for identifying specific pathological states, as targets for therapeutic intervention, in screens of small molecule compounds and/or pharmaceuticals, or for use in cellular or animal models. Thus, the current disclosure includes as an embodiment of the current invention, the cloned nucleic acid sequences, vectors, transfected and/or transformed cell lines, animal models, recombinantly expressed and/or endogenously expressed protein.  
     [1003] The compositions of the present invention will have efficacy for treatment of patients suffering from: cancer; inflammation and autoimmune disorders including Crohn&#39;s disease, IBD, allergies, rheumatoid and osteoarthritis, inflammatory skin disorders, allergies, blood disorders; colon cancer, leukemia AIDS; metabolic disorders including diabetes and obesity; pancreatic disorders including pancreatic insufficiency and cancer; and prostate disorders including prostate cancer and other diseases, disorders and conditions of the like.  
     [1004] In one aspect, the present invention provides a method of identifying novel proteins, protein interactions, complexes, and/or pathways that are candidates for therapeutic intervention in treating a disease, pathology, abnormal state or condition through the targeting of an entity, which has a specific association with the disease. Use of the discovery includes:  
     [1005] 1) use as the basis for a diagnostic or therapeutic intervention for a disease or pathological condition, a protein interaction pair, a complex, collection of interactions, or a pathway that elucidates a previously unappreciated function or biological context for a protein.  
     [1006] 2) use of a protein or protein complex as affinity reagent(s) (e.g. as in co-immunoprecipitation or affinity chromatography) as a means of purification or for the identification of the presence of another protein component of the interaction.  
     [1007] 3) use for monitoring the formation of an interaction pair or complex as an indicator of a drug&#39;s effect, as in the screen of a library of compounds, to identify a particular cellular condition or state.  
     [1008] 4) use for the modulation of one component of the pathway in order to elicit changes in the activity or expression of downstream interactors or genes, resulting in the alteration of a particular phenotype.  
     [1009] 5) use of compounds, such as those identified in a high throughput screen, to perturb or promote the protein interactions themselves.  
     [1010] 6) use, in the case of enzyme/substrate interactions, for monitoring changes in the enzymatic activity and/or generation of the modified substrate as an indicator, such as in a high throughput screen of compounds.  
     [1011] The invention includes the novel protein complexes. An aspect of this invention is a method for the detection of the protein complexes and production of recombinant proteins. This aspect includes a method, which assays for protein-protein interactions, which may include full-length proteins, as well as protein fragments that interact in cell-based (yeast-2-hybrid, co-immunoprecipitation) and in vitro assays (affinity chromatography). In another aspect, the identified protein complexes can be used as a diagnostic in determining a specific disease or pathological condition or state, as well as for detection of a predisposition to a disease or pathological condition. Included in this aspect is a method for the use of labeled or fusion proteins for detection, and/or the use of antibodies specific for the individual proteins or the protein complex. The method measures the ability of the proteins to form the complex, and includes the identification of mutations or single nucleotide polymorphisms (SNPs), which may affect the ability of the proteins to form the complex or function normally. Another part of this aspect includes the use of the complex as a target for the treatment of disease or therapeutic intervention such that promoting or abolishing complex formation will affect its biological function and an overall phenotype. Included, as embodiments are the nucleotide sequences of the proteins, any vector constructs, recombinant protein, monoclonal and polyclonal antibodies, modified cell lines, and animal models.  
     [1012] The invention includes the use of the protein interactors in a complex as affinity reagents. One aspect of this invention includes the use of protein components of the complex in immunoprecipitation experiments to monitor amount of complex formation, as well as to determine the presence or absence of other components of the complex. Antibodies specific for individual components of the complex can be used to pull-down associated proteins in the complex which can then be identified by a second antibody. Basically, the complex can be isolated from native tissue or engineered cell lines expressing the proteins of interest, through antibody or affinity tag specific affinity columns. The presence of the specific complex, or other associated proteins can be determined by staining of electrophoresed proteins, mass spectrometry, or secondary antibodies. An embodiment of this aspect is the use of modified cell lines expressing the proteins or protein fragments of interest, as well as antibodies specific to the proteins and the complexes.  
     [1013] The invention includes a method to monitor protein interactions or formation of the protein complexes as an indicator of specific state or condition in response to treatment with a drug or pharmaceutical. An aspect of this invention includes the use of antibodies, specific for the protein complex, as a reagent in a method to determine the relative abundance of the complex under various conditions or in specific tissues. An embodiment is the use of recombinant proteins, which may be expressed with “epitope” tags in order to easily monitor their expression and interactions.  
     [1014] The invention includes a method to modulate a specific phenotype by modulating protein components or complexes, which occur in a related pathway described herein. This can be achieved through modulation with a drug or antibody or antisense oligos, the activity of a protein or complex, the ability of a protein or complex to interact with its biological partner, or the elimination of a protein from a pathway or a complex. Such changes can be observed through monitoring modulation in gene expression of target genes, or the presence or absence of phenotype specific markers. Included as an embodiment of this aspect are vectors, antibodies, libraries of compounds, gene specific antisense oligonucleotides, and cell lines.  
     [1015] The invention includes the use of the protein complexes in screens of compounds, drugs, and/or pharmaceuticals for identification of chemical agents, which interact with the protein complex and affect the protein-protein interaction itself. As such, the compounds identified can be selected based on their ability to affect the formation of the complex. The use of antibodies specific for the complex can be used to determine the changes, if any, in the amount of complex formed after treatment with a compound versus the untreated controls.  
     [1016] The invention includes a method for screening compounds, which may have effects on the activity of a complex. Associated with this aspect is a method for monitoring the activity of the complex as an indicator of drug action. This can be performed using standard methods of biochemistry and can be measured by changes in the rate of catalytic activity (V Max ) and/or the affinity for substrate (K M ). Antibodies to the modified substrate can be used to assay for changes in the activity of the complex of interest in treated versus controls. As an embodiment of this aspect a library of compounds, drugs and/or pharmaceuticals may be used to select for agents, which modulate the specific protein complex.  
     [1017] Interaction Between Calpain 3 and WNK 1 (Table F1)  
     [1018] The interactions shown in Table F1 illustrate interactions of Calpain 3 with WNK1 and a voltage gated potassium channel modulatory subunit. Calpain 3 is a well-characterized cysteine protease expressed highly in cardiac tissue. Calpain 3 contains several possible sites for phosphorylation by PKA and PKC, but phosphorylation by WNK kinases, specifically WNK1, has not yet been shown. The calcium dependency of Calpain 3 proteolytic activity is well documented, and known targets of Calpain include primarily structural proteins. The voltage gated potassium channel modulatory subunit protein also contains several EF-hand motifs, which likely mediate calcium binding, consistent with calcium-regulated function and suggestive that these interactions mediate important functions in calcium and potassium-dependent cellular events. The current invention reports heretofore-unknown protein interactions involved in prostate-derived STE20-like kinase (PSK or WNK1) signaling. WNK1 is a member of a new family of protein kinases, which contain a cysteine residue instead of the typical lysine in the active site. WNK1 is expressed in many tissues but particularly high levels are found in kidney, cardiac and skeletal muscle. It has also been shown to activate the JNK-MAPK signaling pathway suggesting likely roles in modulating gene expression as well as cell survival. Recent linkage analysis suggests mutations of WNK1 have a role in some forms of hypertension. The interactions identified here are consistent with a role for WNK1 in proper cardiac, and renal function. WNK1 has been recently shown to be cytoplasmic, so the possibility exists that WNK1 activity is modulated through Calpain 3 proteolysis. The ability of Calpain 3 to cleave WNK1 and its associated effects has yet to be shown. However, this could represent an important step in calcium-dependant signaling events related to hypertension and cardiac, skeletal muscle, and kidney function. Additionally, Calpain 3 mediated proteolysis of the voltage gated potassium channel modulatory subunit has also never been shown but provides an intriguing possibility for the modulation of cardiac excitability and performance in response to hypertensive stress. 
 
 
     [1019] The sequence for Calpain 3 is NOV23b, SEQ ID NOS 123 and 124. Calpain 3 can also be known as AF127765. The nucleotide and amino acid sequences for WNK1 (SEQ ID NOS 229 and 230) are as follows:  
                          &gt;WNK1                         SEQ ID:229                         ATGTCTGGCGGCGCCGCAGAGAAGCAGAGCACCACTCCCGGTTCCCTGTTCCTCTCGCCGCCGGCTCCTG                   CCCCCAAGATGGCTCCAGCTCCGATTCCTCCGTGGGGGAGAAACTGGGAGCCGCGGGCCGCCGACCCTGT               GACCGGCAGGACCGAGGAGTACAGGCGCCCCCGCCACACTATGGACAAGGACAGCCGTGGGGCGGCCGCG               ACCACTACCACCACTGAGCACCGCTTCTTCCGCCGGAGCGTCATCTGCGACTCCAATGCCACTGCGCTGG               ASCTTCCCGGCCTTCCTCTTTCCCTGCCCCAGCCCAGCATCCCCGCGGCTGTCCCGCAGAGTGCTCCACC               GGAGCCCCACCGCGAAGAGACCGTGACCGCCACCGCCACTTCCCAGGTAGCCCAGCAGCCTCCAGCCGCT               CCCGCCCCTGGGGAACAGGCCGTCGCGGGCCCTGCCCCCTCGACTGTCCCCAGCACTACCAGCAAAGACC               GCCCAGTGTCCCAGCCTAGCCTTGTQGGGAGCAAAGACGACCCGCCGCCGGCGAGAAGTGGCAGCGGCGG               CCCCAGCCCCAAGGAGCCACAGGAGGAACGGAGCCAGCAGCAGGATGATATCGAAGACCTGGACACCAAG               GCCGTGGGAATGTCTAACGATGCCCGCTTTCTCAACTTTGACATCGAAATCGGCAGAGGCTCCTTTAAGA               CGCTCTACAAAGGTCTGGACACTGAAACCACCGTGGAAGTCGCCTGGTGTGAACTGCAGGATCGAAAATT               AACAAAGTCTGAGAGGCAGAGATTTAAAGAAGAAGCTGAAATGTTAAAAGGTCTTCAGCATCCCAATATT               GTTAGATTTTATGATTCCTGGGAATCCACAGTAAAAGGAAAGAAGTGCATTGTTTTGCTGACTGAACTTA               TGACGTCTGGAACACTTAAAACGTATCTGAAAAGGTTTAAAGTGATCAAGATCAAAGTTCTAAGAAGCTG               GTGCCGTCAGATCCTTAAAGGTCTTCAGTTTCTTCATACTCGAACTCCACCTATCATTCACCGCGATCTT               AAATGTGACAACATCTTTATCACCGGCCCTACTGGCTCAGTCAACATTGGAGACCTCGGTCTGGCAACCC               TGAAGCGCGCTTCTTTTGCCAAGAGTGTGATAGGTACCCCAGAGTTCATGGCCCCTGAGATGTATGAGGA               GAAATATGATGAATCCGTTGACGTTTATGCCTTTGGGATGTGCATGCTTGAGATGGCTACATCTGAATAT               CCTTACTCCGAGTGCCAAAATDCTGCGCAGATCTACCGTCGCGTGACCAGTGGGCTGAAGCCAGCCAGTT               TTGACAAAGTAGCAATTCCTGAAGTGAAGGAAATTATTGAAGGATGCATACGACAAAACAAAGATGAAAG               ATATTCCATCAAACACCTTTTGAACCATGCCTTCTTCCAAGAGGAAACAGGAGTACGGGTAGAATTAGCA               CAGGAAGATGATGGAGAAAAAATAGCCATAAAATTATGGCTACGTATTGAAGATATTAAGAAATTAAAGG               GAAAATACAAAGATAATGAAGCTATTGAGTTTTCTTTTGATTTAGAGAGAGATGTCCCAGAAGATGTTCC               ACAAGAAATGGTAGAGTCTGGGTATGTCTGTGAAGCTGATCACAAGACCATGGCTAAAGCTATCAAAGAC               AGAGTATCATTAATTAAGAGGAAACGACAGCAGCGGCAGTTGGTACGGGAGGAGCAAGAAAAAAAAAAGC               AGCAAGACAGCAGTCTCAAACAGCAGGTAGAACAATCCAGTGCTTCCCAGACAGGAATCAAGCAGCTCCC               TTCTGCTAGCACCCGCATACCTACTGCTTCTACCACTTCADCTTCAGTTTCTACACAAGTAGAACCTGAA               GAACCTCAGGCACATCAACATCAACAACTACAGTACCAGCAACCCAGTATATCTGTGTTATCTCATGGGA               CGGTTGACAGTGGTCAGGGATCCTCTGTCTTCACAGAATCTCCAGTGASCAGCCAACAGACAGTTTCATA               TCGTTCCCAACATCAACAGGCACATTCTACAGGCACAGTCCCAGGGCATATACCTTCTACTGTCCAAGCA               CAGTCTCAGCCCCATGGGGTATATCCACCCTCAAGTGTGGCACAGGGCCAGAGCCAGGGTCAGCCATCCT               CAACTAGCTTAACAGGGGTTTCATCTTCCCAACCCATACAACATCCTCAGCAGCAGCAGCGAATACAGCA               GACAGCCCCTCCTCAACAGACAGTGCAGTATTCACTTTCACAGACATCAACCTCCAGTGAGGCCACTACT               GCACAGCCAGTGAGTCAGCCTCAAGCTCCACAAGTCTTGCCTCAAGTATCAGCTGGAAAACAGCTTCCAG               TTTCCCAGCCACTACCAACTATCCAAGGCGAACCTCAGATCCCAGTTGCGACACAACCCTCGGTTGTTCC               AGTCCACTCTGGTGCTCATTTCCTTCCAGTGCGACAGCCGCTCCCTACTCCCTTGCTCCCTCAGTACCCT               GTCTCTCAGATTCCCATATCAACTCCTCATGTGTCTACGGCTCAGACAGGTTTCTCATCCCTTCCCATCA               CAATGCCAGCTGGCATTACTCAGCCTCTGCTCACGTTGGCTTCATCTGCTACAACAGCTGCCATCCCGCG               GGTATCAACTGTGGTTCCTAGTCAGCTTCCAACCCTTCTGCAGCCTGTGACTCAGCTGCCAAGTCAGGTT               CACCCACAGCTCCTACAACCAGCAGTTCAGTCCATGGGAATACCAGCTAACCTTGGACAAGCTGCTGAGG               TTCCACTTTCCTCTGGAGATGTTCTGTACCAGGGCTTCCCACCTCGACTCCCACCACAGTACCCAGGAGA               TTCAAATATTGCTCCCTCTTCCAACGTGGCTTCTGTTTGCATCCATTCTACAGTCCTATCCCCTCCCATG               CCGACAGAAGTACTGGCTACACCTGCCTACTTTCCCACACTCCTGCAGCCTTATGTGGAATCAAATCTTT               TAGTTCCTATGGGTCGTGTAGGAGGACAGGTTCAAGTGTCCCAGCCAGGAGGCAGTTTAGCACAAGCCCC               CACTACATCCTCCCAGCAAGCAGTTTTGGAGAGTACTCAGGGAGTCTCTCAGGTTCCTCCTGCACACCCA               GTTGCAGTAGCACAGCCCCAAGCTACCCAGCCGACCACTTTGGCTTCCTCTGTAGACAGTGCACATTCAG               ATGTTGCTTCAGGTATGAGTGATGGCAATDACAACCTCCCATCTTCCAGTGGAAGGCATGAAGGAAGAAC               TACAAAACGGCATTACCGAAAATCTGTAAGGAGTCGCTCTCGACATGAAAAAACTTCACGCCCAAAATTA               AGAATTTTGAATGTTTCAAATAAAGGAGACCGAGTAGTAGAATGTCAATTAGAGACTCATAATAGGAAAA               TGGTTACATTCAAATTTGACCTAGATGGTGACAACCCCGAGGACATAGCAACAATTATGGTGAACAATGA               CTTTATTCTAGCAATAGAGAGAGAGTCGTTTGTGGATCAAGTGCGAGAAATTATTGAAAAAGCTGATGAA               ATGCTCAGTGAGGATGTCAGTGTGGAACCAGAGGGTGATCAGGGATTGGAGAGTCTACAAGGAAACGATC               ACTATGGCTTTTCAGGTTCTCAGAAATTGGAAGGAGAGTTCAAACAACCAATTCCTGCGTCTTCCATGCC               ACAGCAAATAGGCATTCCTACCAGTTCTTTAACTCAAGTTGTTCATTCTGCGGGAAGGCGGTTTATAGTG               AGTCCTGTGCCAGAAAGCCGATTACGAGAATCAAAAGTTTTCCCCAGTGAAATAACAGATACAGTTGCTG               CCTCTACAGCTCAGAGCCCTGGAATGAACTTGTCTCACTCTGCATCATCCCTTAGTCTACAACAGGCCTT               TTCTGAACTTAGACGTGCCCAAATGACAGAAGGACCCAACACAGCACCTCCAAACTTTAGTCATACAGGA               CCAACATTTCCAGTAGTACCTCCTTTCTTAAGTAGCATTGCTGGAGTCCCAACCACAGCAGCAGCCACAG               CACCAGTCCCTGCAACAAGCAGCCCTCCTAATGACATTTCCACATCAGTAATTCAGTCTGAGGTTACAGT               GCCCACTCAAGACGGGATTGCTGGAGTTGCCACCAGCACAGGTGTGGTAACTTCACGTGCTCTCCCCATA               CCACCTGTGTCTGAATCACCAGTACTTTCCAGCGTAGTTTCAAGTATCACAATACCTGCAGTTGTCTCAA               TATCTACTACATCCCCCTCACTTCAAGTCCCCACATCCACATCTGAGATCGTTGTTTCTAGTACAGCACT               GTATCCTTCAGTAACAGTTTCAGCAACTTCAGCCTCTGCAGGGGGCAGTACTGCTACCCCAGGTCCTAAG               CCTCCAGCTGTAGTATCTCAGCAGGCAGCAGGCAGCACTACTGTGGGAGCCACATTAACATCAGTTTCTA               CCACCACTTCATTCCCAAGCACAGCTTCACAGCTGTCCATTCACCTTAGCAGCAQTACTTCTACTCCTAC               TTTAGCTGAAACCGTGGTAGTTAGCGCACACTCACTAGATAAGACATCTCATAGCAGTACAACTGGATTG               GCTTTCTCCCTCTCTGCACCATCTTCCTCTTCCTCTCCTGGAGCAGGAGTGTCTAGTTATATTTCTCAGC               CTGGTGGGCTGCATCCTTTGGTCATTCCATCAGTGATAGCTTCTACTCCTATTCTTCCCCAAGCAGCAGG               ACCTACTTCTACACCTTTATTACCCCAAGTACCTAGTATCCCACCCTTGGTACAGCCTGTTGCCAATGTG               CCTCCTGTACACCAGACACTAATTCATAGTCAGCCTCAACCAGCTTTGCTTCCCAACCAGCCCCATACTC               ATTGTCCTGAAGTAGATTCTGATACACAACCCAAAGCTCCTGGAATTGATGACATAAAGACTCTAGAAGA               AAAGCTGCGGTCTCTGTTCAGTGAACACAGCTCATCTGGAGCTCAGCATCCCTCTGTCTCACTGGAGACC               TCACTAGTCATAGAGAGCACTGTCACACCAGGCATCCCAACTACTGCTGTTGCACCAAGCAAACTCCTGA               CTTCTACCACAAGTACTTGCTTACCACCAACCAATTTACCACTAGGAACAGTTGCTTTGCCAGTTACACC               AGTCGTCACACCTGGGCAAGTTTCTACCCCAGTCAGCACTACTACATCAGGAGTGAAACCTGGAACTCCT               CCCTCCAAGCCACCTCTAACTAAGGCTCCGGTCCTCCCAGTGCGTACTGAACTTCCAGCAGGTACTCTAC               CCAGCGAGCACCTCCCACCTTTTCCAGGACCTTCTCTAACCCAGTCCCAQCAACCTCTACAGGATCTTGA               TGCTCAATTGAGAAGAACACTTAGTCCAGAGATTATCACACTGACTTCTGCGGTTGGTCCTGTGTCCATG               GCGGCTCCAACACCAATCACAGAAGCAGGAACACAGCCTCAGAAGGGTGTTTCTCAAGTCAAAGAAGCCC               CTGTCCTAGCAACTAGTTCAGGAGCTGGTGTTTTTAAGATGGGACGATTTCAGGTTTCTGTTGCAGCAGA               CGGTGCCCAGAAAGAGGGTAAAAATAAGTCAGAAGATGCAAAGTCTGTTCATTTTGAATCCAGCACCTCA               GAGTCCTCAGTGCTATCAAGTAGTAGTCCAGACAGTACCTTGGTGAAACCAGAGCCGAATGGCATAACCA               TCCCTCGTATCTCTTCAGATGTGCCAGAGAGTGCCCACAAAACTACTGCCTCAGAGGCAAAGTCAGACAC               TGGGCAGCCTACCAAGGTTGGACGTTTTCAGGTGACAACTACAGCAAACAAAGTGGGTCGTTTCTCTGTA               TCAAAAACTGAGCACAAGATCACTGACACAAAGAAACAAGGACCAGTCGCATCTCCTCCTTTTATCCATT               TGGAACAAGCTGTTCTTCCTGCTGTGATACCAAAGAAAGAGAAGCCTGAACTGTCAGAGCCTTCACATCT               AAATGGCCCGTCTTCTGACCCGCAGGCCGCTTTTTTAAGTACCGATCTCGATCATGGTTCCGGTAGTCCA               CACTCGCCCCATCAGCTGAGCTCAAAGAGCCTTCCTAGCCAGAATCTAAGTCAAAGCCTTAGTAATTCAT               TTAACTCCTCTTACATGAGTAGCGACAATGAGTCACATATCCAAGATGAAGACTTAAAGTTAGAGCTGCG               ACGACTACGAGATAAACATCTCAAAGAGATTCAGGACCTGCAGAGTCGCCAGAAGCATGAAATTGAATCT               TTGTATACCAAACTGGGCAAGGTGCCCCCTGCTGTTATTATTCCCCCACCTGCTCCCCTTTCAGGGAGAA               GACGACGACCCACTAAAAGCAAAGGCAGCAAATCTAGTCGAAGCAGTTCCTTGGGGAATAAAAGCCCCCA               GCTTTCAGGTAACCTGTCTGCTCACAGTGCAGCTTCAGTCTTCCACCCCCAGCAGACCCTCCACCCTCCT               GGCAACATCCCACAGTCCGGGCAGAATCAGCTGTTACAGCCCCTTAAGCCATCTCCCTCCAGTGACAACC               TCTATTCAGCCTTCACCAGTGATGGTGCCATTGCAGTACCAAGCCTTTCTGCTCCAGGTCAAGGAACCAG               CACCACAAACACTGTTCCGCCAACAGTGAACAGCCAAGCCGCCCAAGCTCAGCCTCCTGCCATGACGTCC               AGCAGGAAGGGCACATTCACAGATGACTTGCACAAGTTGGTAGACAATTGGGCCCGAGATGCCATGAATC               TCTCAGGCACGAGAGCAAGCAAACGGCACATGAATTACGAGGGCCCTGGAATGGCAAGGAAGTTCTCTGC               ACCTCCGCAACTGTGCATCTCCATGACCTCGAACCTGGGTGGCTCTGCCCCCATCTCTGCAGCATCAGCT               ACCTCGCTAGGTCACTTCACCAAGTCTATGTGCCCCCCACAGCAGTATGGCTTTCCAGCTACCCCATTTG               GCGCTCAATGGAGTGGGACCGGTGCCCCAGCACCACAGCCACTTCGCCAGTTCCAACCTGTGGCAACTGC               CTCCTTGCAGAATTTCAACATCAGCAATTTGCAGAAATCCATCAGCAACCCCCCAGGCTCCAACCTCCCC               ACCACTTAG               &gt;WNK1                     SEQ ID:230                         MSGGAAEKQSSTPGSLFLSPPAPAPKNGSSSDSSVGEKLGAAAADAVTGRTEEYRRRRHTMDKDSRGAAA                   TTTTTEHRFFRRSVICDSNATALELPGLPLSLPQPSIPAAVPQSAPPEPHREETVTATATSQVAQQPPAA               AAPGEQAVAGPAPSTVPSSTSKDRPVSQPSLVGSKEEPPPARSGSGGGSAKEPQEERSQQQDDIEELETK               AVGMSNHGRFLKFDIEIGRGSFKTVYKGLDTETTVEVAWCELQDRKLTKSERQRFKEEAEMLKGLQHPNI               VRFYDSWESTVKGKKCIVLVThLMTSGTLKTYLKRFKVMKIKVLRSWCRQILKGLQFLHTRTPPIIHRDL               KCDNIFITCPTGSVKIGDLGLATLKASFAKSVIGTPEFMAPEMYEEKYDESVDVYAFGMCMLEMNATSEY               PYSECQNAAQIYRRVTSGVKPASFDKVAIPEVKEIIEGCIRQNKDERYSIKDLLNHAFFQEETGVRVELA               EEDDGEKIAIKLWLRIEDIKKLKGKYKDAEAIEFSFDLERDVPEDVAQEMVESGYVCEGDHKTMAKAIKD               RVSLIKRKREQRQLVREEQEKKKQEESSLKQQVEQSSASQTGIKQLPSASTGIPTASTTSASVSTQVEPE               EPEADQHQQLQYQQPSISVLSDGTVDSGQGSSVFTESRVSSQQTVSYGSQHEQAHSTGTVPGHIPSTVQA               QSQPHGVYPPSSVAQGQSQGQPSSSSLTGVSSSQPIQHPQQQQGIQQTAPPQQTVQYSLSQTSTSSEATT               AQPVSQPQAPQVLPQVSAGKQLPVSQPVPTIQGEPQIPVATQPSVVPVHSGAHFLPVGQPLPTPLLPQYP               VSQIPISTPHVSTAQTGFSSLPITMAACITQPLLTLASSATTAAIPGVSTVVPSQLPTLLQPVTQLPSQV               HPQLLQPAVQSMGTPANLGQAAEVPLSSGDVLYQGFPPRLPPQYPGDSNIAPSSNVASVCIHSTVLSPPM               PTEVLATPGYFPTVVQPYVESNLLVPMGGVGGQVQVSQPGGSLAQAPTTSSQQAVLESTQGVSQVAPAEP               VAVAQPQATQPTTLASSVDSAHSDVASGMSDGNSNVPSSSGRHEGRTTKRHYRKSVRSRSRHEKTSRPKL               RILNVSNKGDRVVECQLETHNRKMVTFKFDLDGDNPEEIATIMVNNDFILAIERESFVDQVREITEKADE               MLSEDVSVEPEGDQGLESLQGKDDYGFSGSQKLEGEFKQPIPASSMPQQIGIPTSSLTQVVHSAGRRFIV               SPVPESRLRESKVFPSEITDTVAASTAQSPGMNLSHSASSLSLQQAFSELRRAQMTEGPNTAPPNFSHTG               PTFPVVPPFLSSIAGVPTTAAATAPVPATSSPPNDISTSVIQSEVTVPTEEGIAGVATSTGVVTSGGLPI               PPVSESPVLSSVVSSITIPAVVSISTTSPSLQVPTSTSEIVVSSTALYPSVTVSATSASAGGSTATPGPK               PPAVVSQQAAGSTTVGATLTSVSTTTSFPSTASQLSIQLSSSTSTPTLAETVVVSAHSLDKTSHSSTTCL               AFSLSAPSSSSSPGAGVSSYISQPCGLHPLVIPSVTASTPILPQAAGPTSTPLLPQVPSIPPLVQPVANV               PAVQQTLIHSQPQPALLPNQPHTHCPEVDSDTGPKAPGIDDIKTLEEKLRSLFSEHSSSGAQHASVSLET               SLVIESTVTPGIPTTAVAPSKLLTSTTSTCLPPTNLPLGTVALPVTPVVTPGQVSTPVSTTTSGVKPGTA               PSKPPLTKAPVLPVGTELPAGTLPSEQLPPFPGPSLTQSQQPLEDLDAQLRRTLSPEIITVTSAVGPVSM               AAPTAITEAGTQPQKGVSQVKEGPVLATSSGAGVFKMGRFQVSVAADGAQKEGKNKSEDAKSVHFESSTS               ESSVLSSSSPESTLVKPEPNCITTPGISSDVPESAHKTTASEAKSDTGQPTKVGRFQVTTTANKVGRFSV               SKTEDKITDTKKEGPVASPPFMDLEQAVLPAVIPKKEKPELSEPSHHNGPSSDPEAAFLSRDVDDGSGSP               HSPHQLSSKSLPSQWLSQSLSNSFNSSYMSSDNESDIEDEDLKLELRRLRDKHLKEIQDLQSRQKHEIES               LYTKLCKVPPAVTIPPAAPLSGRRRRPTKSKGSKSSRSSSLGNKSPQLSGNLSGQSAASVLHPQQTLHPP               GNIPESGQNQLLQPLKPSPSSDNLYSAFTSDGAISVPSLSAPGQGTSSTNTVGATVNSQAAQAQPPAMTS               SRKGTFTDDLHKLVDNWARDAMNLSGRRGSKGHMNYEGPGMARKFSAPGQLCISMTSNLGGSAPISAASA               TSLGHFTKSMCPPQQYGFPATPFCAQWSGTCCPAPQPLCQFQPVCTASLQFNISNGLQKSISMPPCSMLR               TT          
 
     [1020] Segments of Each Protein Used in Y-2-H Screen (Table F2) 
 
 
     [1021] The interaction of Calpain 3 with WNK1 is mediated by several hundred amino acids in the extreme carboxy-terminus. This region is distinct from the catalytic site of WNK1 (at least in terms of primary structure), and may hence represent either an interaction event which is necessary for subsequent WNK1-dependent phosphorylation of Calpain 3, Calpain 3-dependent proteolytic cleavage of WNK1, or possibly an interaction event independent of their respective catalytic activities but is critical to proper signaling events or localization. We can hypothesize that the interaction of Calpain 3 with the voltage dependent potassium channel modulatory subunit likely represents a proteolytic event, which would result in altered function of potassium channel functions. Precise determination of the sites of interaction of Calpain 3 with either protein remains to be identified. Additional information concerning Calpain 3 is the identification by CuraGen Corporation of a novel splice form, which contains a 48 amino acid deletion (aa 268-315) within the cysteine protease domain. In addition to its known expression in cardiac tissue, RTQ analysis of Calpain 3 indicate that expression is observed in skeletal muscle, kidney, and lung epithelium activated by exposure to TNF-alpha. The proteins and interactions disclosed herein represent plausible therapeutic targets for the treatment of hypertension, heart disease, pseudohypoaldosteronism type II, hyperkalemia, emphysema, asthma as well as others.  
     [1022] Method of Identifying the Nucleic Acids and Proteins, which Constitute the Interactions of this Invention.  
     [1023] PathCalling™ 
     [1024] The sequence of PRKWNK1, Calpain 3, and voltage dependent potassium channel modulatory subunit were derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full-length DNA sequence, or some portion thereof.  
     [1025] The laboratory cloning was performed using one or more of the methods summarized below:  
     [1026] cDNA libraries were derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then directionally cloned into the appropriate two-hybrid vector (Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, Calif.) were then transferred from  E. coli  into a CuraGen Corporation proprietary yeast strain (disclosed in U.S. Pat. Nos. 6,057,101 and 6,083,693, incorporated herein by reference in their entireties).  
     [1027] Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corporation proprietary library of human sequences was used to screen multiple Gal4-AD fusion cDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Gal4-AD fusion contains an individual cDNA. Each sample was amplified using the polymerase chain reaction (PCR) using non-specific primers at the cDNA insert boundaries. Such PCR product was sequenced; sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation&#39;s database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.  
     [1028] Physical clone: the cDNA fragment derived by the screening procedure, covering the entire open reading frame is, as a recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library. The recombinant plasmid is inserted into the host and selected by the yeast hybrid diploid generated during the screening procedure by the mating of both CuraGen Corporation proprietary yeast strains N106′ and YULH (U.S. Pat. Nos. 6,057,101 and 6,083,693) to provide the clones.  
     [1029] Interaction protein pairs are added to CuraGen&#39;s PathCalling™ Protein Interaction Database. This database allows for the discovery of novel pharmaceutical drug targets by virtue of their interactions and/or presence in pathologically related signaling pathways. Protein interactions are subsequently analyzed using bioinformatic tools within GeneScape™, which provides a means of visualization of binary protein interactions, protein complex formation, as well as complete cellular signaling pathways. Specifically, the sequences, which encode PRKWNK1, Calpain 3, and voltage dependent potassium channel modulatory subunit proteins were found to interact and may result in the formation of a protein complex, or may constitute a series of complexes, which form in order to propagate a cellular signal, which is physiologically relevant to a disease pathology. The specific interactions, which constitute the specific complexes, may also be useful for therapeutic intervention through the use of recombinant protein or antibody therapies, small molecule drugs, or gene therapy approaches. Protein interactions, which are identified through the mining of the PathCalling™ database, can be screened in vitro and in vivo to provide expression, functional, biochemical, and phenotypic information. Assays may be used alone or in conjunction and include, but are not limited to the following technologies; RTQ-PCR, Transfection of recombinant proteins, Co-immunoprecipitation and mass spectrometry, FRET, Affinity Chromatography, Immunohistochemisty or Immunocytochemistry, gene CHIP hybridizations, antisense (i.e. knock-down, knock-up), GeneCalling experiments, and/or biochemical assays (phosphorylation, dephosphorylation, protease, etc.).  
     [1030] SeqCalling™ Technology  
     [1031] cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then sequenced using CuraGen&#39;s proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation&#39;s database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.  
     [1032] Uses of the Compositions of the Invention.  
     [1033] The interaction complexes of Calpain 3 and their relevance to WNK1 and in general to Calpain 3 and WNK1 signaling, provides opportunities to develop tools against various pathologic situations in which signaling through Calpain 3 and WNK1 proteins and Calpain 3 and WNK1 protein complexes are involved. Therefore, the 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, a means of isolation by virtue of the interacting partners, 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.  
     [1034] The yeast-2-hybrid system was used to identify the interacting proteins disclosed in the present invention. The proteins involved in these interactions likely participate in the same physiological pathway. Because of the significance of these pathways, the present invention provides a list of uses for these proteins and/or the DNA encoding these proteins, as a basis for developing therapeutic and diagnostic tools. This list includes but is not limited to the following examples.  
     [1035] Mass Spectrometry (MS)  
     [1036] For detailed descriptions of mass spectrometry methods see Bonk and Humeny,  Neuroscientist,  2001; Gygi and Aebersold,  Curr Opinion in Chem Biol,  2000; or Gygi et al.,  Nature Biotechnology,  1999. Below is a brief description of several MS approaches, which could be employed to assay for protein interactions, modifications and protein compositions.  
     [1037] Mass Spectrometry is based on the measurement of the mass to charge (m/z) ratio of gas-phase ions. For proteins or peptides this means that they must first be ionized and then vaporized in order for the m/z ratio to be determined. Mass spectrometry is amenable to automation and useful for the identification of low abundance proteins (pico-to zeptomole range), large proteins, peptides, and identification of protein modifications. MS is also useful for the identification of protein interactions and complexes even if the kinetics are relatively fast since desorption occurs on the order of milliseconds.  
     [1038] One method is matrix-assisted laser-desorption-ionization (MALDI) coupled with time-of-flight (TOF) MS analysis, so called MALDI-TOF. This method involves the use of a light-absorbing matrix, which results in the vaporization of sample molecules and analysis of mass as a function of desorption time. A related technique is surface-enhanced laser desorption ionization (SELDI)-TOF, which has the advantage of not requiring the purification of proteins by using a surface with a defined chemical chromatographic characteristic (e.g. hydrophobic, hydrophilic, cationic, anionic) or biochemical ligands such as proteins, receptors, antibodies, or DNA oligonucleotides. Another variation is tandem mass spectrometry such as the nanoelectrospray (ES) MS/MS, which is the optimum method for ionization/vaporization for the widest range of molecules. To maximize the advantages of various MS methods, the best approach seems to be a hybrid, such as using a tandem array of MALDI ionization or ES coupled with quadrupole-TOF (MS 1 ) with orthogonal arranged reflectron TOF (MS 2 ) (Micromass Q-TOF), (for detailed methods see Fandrich et al., 2000). Isotope-coded affinity tag (ICAT) modified proteins combined with protease digestion, microcapillary liquid chromatography and ES MS/MS, allows for the quantification and concurrent sequence identification of individual proteins in complex mixtures even if they are present at low relative abundance. The most recent advance in MS is the electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTIR MS), which allows protein identification by accurate mass measurement of a single cysteine-containing peptide and has been shown to be sensitive enough to detect proteins present on the order of 1 ppm (Goodlett et al., 2000).  
     [1039] Functional Assays  
     [1040] Interesting two hybrid interactions involving proteins that have enzymatic activities can be validated by cellular assays. Modifications such as phosphorylation, dephosphorylation, proteolysis, ubiquitination, sumoylation, and acetylation can be analyzed by western blotting using specific antibodies.  
     [1041] Some of the modifications described above can be analyzed in a yeast system. Yeast cells expressing the two interacting proteins, as activation domain (AD) or DNA binding domain (BD)-fusion proteins are grown, and cell extracts are prepared by lysing the cells appropriately. The substrate protein which is expected to be modified, is immunoprecipitated using antibodies specific to the AD or the BD domains. The immunoprecipitates are separated on SDS-PAGE and western blotted using specific antibodies. For identifying phosphorylated proteins, antibodies specific for phospho-tyrosine, or phospho-serine/threonine is used. Similarly, to detect modification by ubiquitination or sumoylation, antibodies specific to these proteins can be used. For proteolysis, the alteration in the mobility of the target protein (change in molecular mass) can be taken as a positive indication for a valid interaction. For each of the assays, control yeast strains expressing only one of the proteins are processed to show that in the absence of the interacting enzyme the substrate protein does not undergo any modification.  
     [1042] To produce yeast lysates, Remove 1-1.5 ml samples from a yeast culture, freeze samples on dry ice. On ice, add of low-salt lysis Buffer to the cell pellets. Add glass beads, resuspend the cells by a brief vortexing. Lyse the cells by beating the beads for 90 sec. Put the lysate on ice for 5 min and beat the beads again for 90 sec. Put the sample back on ice. Once the lysate has been recovered free of beads, centrifuge the lysate at maximum speed in a microcentrifuge for 3 to 5 min at 4° C. and put the samples on ice. Remove 25 to 50 μl of the supernatant and mix with an equal volume of 2× Protein Sample Buffer and save for Western analysis.  
     [1043] Immunoprecipitation from yeast: Thaw the lysate samples and put the desired volume (based on the protein concentration) into a fresh microcentrifuge tube. Make all the samples the same volume with fresh low-salt lysis Buffer. Add the antibody diluted in Low-Salt Lysis Buffer (10 μl per sample) and mix by vortexing. Incubate on ice for 30 min.  
     [1044] ProteinA-Sepharose/Antibody Binding: Equilibrate protein A-Sepharose beads with low-salt lysis Buffer by suspending the beads in low-salt Buffer, centrifuging briefly to sediment the beads and removing the supernatant. Repeat this equilibration wash step 2 or 3 times. Aliquot the Buffer-equilibrated beads into fresh 0.5 ml microcentrifuge tubes making sure that all the tubes have an equal amount of beads. Centrifuge the antibody/extract mixture in a microcentrifuge at full speed for 1 min at 4° C. Recover the supernatant and add it on to the proteinA-Sepharose. Mix in an end-over-end rotator for 1 to 2 hr at 4° C. Centrifuge briefly in a microcentrifuge (bring centrifuge up to full speed and then back down) and remove the supernatant. Keeping the samples on ice as much as possible, wash the beads by adding 400 μl of bead Buffer. Resuspend the beads and centrifuge again. Remove the supernatant. Resuspend the beads in bead Buffer and transfer mixture to a fresh tube and rinse the old tube with more bead-Buffer to recover residual beads to the new tube. Centrifuge the beads, remove the supernatant and wash the beads with Bead Buffer again. If the immunoprecipitate is only for analysis of radio-labeled proteins bound, the beads can be simply resuspended in protein sample Buffer, boiled for 90 sec and electrophoresed. If an enzymatic assay of some sort is involved, the beads should be washed in the reaction Buffer 1 or 2 times.  
     [1045] In cases where interactions cannot be validated in the yeast system, the interacting proteins are tagged with different epitopes at the N or the C-terminus and expressed in appropriate mammalian cell lines by transient transfection. The cells are grown for 48-72 h, lysed, and the substrate protein is immunoprecipitated using antibody specific to the epitope and analyzed by western blotting as described for the yeast system.  
     [1046] Fluorescence Resonance Energy Transfer  
     [1047] Fluorescence resonance energy transfer (FRET) microscopy is a convenient method for studying protein interactions, and the localization of proteins under physiological conditions. FRET requires the use of two fluorophores (a donor and an acceptor), which demonstrate some overlap in their excitation/emission spectra. Excitation of the donor results in light emission of the acceptor, with a concomitant decrease in emission from the donor, provided the spatial separation of the fluorophores is no more than 10 nm. Because FRET is a nondestructive spectroscopic method for measuring protein interactions, it can be done in living cells, either primary cultured cells or immortalized cell lines. The fluorescence lifetime method allows one to monitor FRET signals at the moment of the protein interactions at a resolution on the order of subnanoseconds, providing high temporal, as well as spatial resolution. One method for detecting molecular interactions involves fluorescence resonance energy transfer (FRET) between two GFPs expressed as fusion proteins with the proteins of interest (such as Cyan FP and Yellow FP) or between GFP and a second fluorophore. In the case of CFP-YFP, excitation of the donor, CFP, occurs at 440 nm and emission at 490 nm, while for the acceptor, YFP, excitation is 450 and emission at 535 nm. FRET occurs through exposure of excitation light to the donor at 440 nm, and subsequent measure of the emission of the acceptor at 535 nm. Because these intrinsically fluorescent proteins are extraordinarily stable, they can be used in fusion protein constructs to monitor protein interactions with little concern for their interfering with the fused domain or protein of interest. FRET is defined as the ratio of emission at 535/485 nm, indicating the extent to which YFP is emitting light due to excitation by CFP.  
     [1048] Other Embodiments  
     [1049] 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. 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.  
 
    
     
       
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                 SEQUENCE LISTING 
               
            
           
           
               
            
               
                 The patent application contains a lengthy “Sequence Listing” section. A copy of the “Sequence Listing” is available in electronic form from the USPTO 
               
               
                 web site (http://seqdata.uspto.gov/sequence.html?DocID=20040043929). An electronic copy of the “Sequence Listing” will also be available from the 
               
               
                 USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).