Novel nucleic acid sequences encoding adenylate kinases, alcohol dehydrogenases, ubiquitin proteases, lipases, adenylate cyclases, and GTPase activators

Abstract

The invention provides isolated nucleic acids molecules that encode novel polypeptides. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a sequence of the invention has been introduced or disrupted. The invention still further provides isolated proteins, fusion proteins, antigenic peptides and antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

1 . An isolated nucleic acid molecule selected from the group consisting of:
 a) a nucleic acid molecule comprising a nucleotide sequence that is at least 60% identical to the nucleotide sequence set forth in SEQ ID NO:1, 6, 8, 10, 12, 14, 16, 18, 20, 21, 23, 24, or 26, or the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918, wherein said nucleotide sequence encodes a polypeptide having biological activity;   b) a nucleic acid molecule comprising a fragment of at least 20 contiguous nucleotides of the nucleotide sequence set forth in SEQ ID NO:1, 6, 8, 10, 12, 14, 16, 18, 20, 21, 23, 24, or 26, or the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918;   c) a nucleic acid molecule encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25 or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918;   d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25 or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918;   e) a nucleic acid molecule encoding a biologically active variant of the amino acid sequence set forth in SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25 or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, or PTA-1871, or PTA-1918, wherein the nucleic acid molecule hybridizes the complement of the nucleotide sequence set forth in SEQ ID NO:1, 6, 8, 10, 12, 14, 16, 18, 20, 21, 23, 24, or 26, or the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918 under stringent conditions; and   f) a nucleic acid molecule comprising the complement of the nucleic acid molecule of a), b), c), d), or e).   
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule is selected from the group consisting of:
 a) a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1, 6, 8, 10, 12, 14, 16, 18, 20, 21, 23, 24, or 26, or a complement thereof;   b) a nucleic acid molecule comprising the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, or PTA-1871;   c) a nucleic acid molecule encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, or a complement thereof; and   d) a nucleic acid molecule encoding the polypeptide encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, or PTA-1871.   
     
     
         3 . The nucleic acid molecule of  claim 1 , further comprising vector nucleic acid sequences. 
     
     
         4 . The nucleic acid molecule of  claim 1  further comprising nucleic acid sequences encoding a heterologous polypeptide. 
     
     
         5 . A host cell that contains the nucleic acid molecule of  claim 3 . 
     
     
         6 . An isolated polypeptide selected from the group consisting of:
 a) a biologically active polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO:1, 6, 8, 10, 12, 14, 16, 18, 20, 21, 23, 24, or 26, or the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918;   b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising the complement of SEQ ID NO:1, 6, 8, 10, 12, 14, 16, 18, 20, 21, 23, 24, or 26, or the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918 under stringent conditions; and,   c) a fragment of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918, wherein the fragment comprises at least 15 contiguous amino acids of the amino acid sequence set forth in SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918; and   d) a polypeptide having at least 60% sequence identity to the amino acid sequence SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, wherein the polypeptide has biological activity.   
     
     
         7 . The isolated polypeptide of  claim 6  comprising the amino acid sequence of SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25. 
     
     
         8 . The polypeptide of  claim 6  further comprising heterologous amino acid sequences. 
     
     
         9 . An antibody which selectively binds to a polypeptide of  claim 6 . 
     
     
         10 . A method for producing a polypeptide selected from the group consisting of:
 a) a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918;   b) a polypeptide comprising a fragment of the amino acid sequence set forth in SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918;   c) a biologically active variant of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, or the amino acid sequence encoded by the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising the complement of SEQ ID NO:1, 6, 8, 10, 12, 14, 16, 18, 20, 21, 23, 24, or 26, or the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1850, PTA-2170, PTA-2812, PTA-2171, PTA-2813, PTA-2011, PTA-2012, PTA-2341, PTA-1849, PTA-1915, PTA-1871, or PTA-1918; and   d) a polypeptide having at least 60% sequence identity to the amino acid sequence of SEQ ID NO:2, 5, 7, 9, 11, 13, 15, 17, 19, 22, or 25, wherein said polypeptide has biological activity;   
       comprising culturing the host cell of  claim 5  under conditions in which the nucleic acid molecule is expressed. 
     
     
         11 . A method for detecting the presence of a polypeptide of  claim 6  in a sample, comprising:
 a) contacting the sample with a compound which selectively binds to a polypeptide of  claim 6 ; and   b) determining whether the compound binds to the polypeptide in the sample.   
     
     
         12 . The method of  claim 11 , wherein the compound which binds to the polypeptide is an antibody. 
     
     
         13 . A kit comprising a compound which selectively binds to a polypeptide of  claim 6  and instructions for use. 
     
     
         14 . A method for detecting the presence of a nucleic acid molecule of  claim 1  in a sample, comprising the steps of:
 a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule; and   b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample.   
     
     
         15 . The method of  claim 14 , wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe. 
     
     
         16 . A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of  claim 1  and instructions for use. 
     
     
         17 . A method for identifying a compound that binds to a polypeptide of  claim 6  comprising the steps of:
 a) contacting a polypeptide, or a cell expressing a polypeptide of  claim 6  with a test compound; and   b) determining whether the polypeptide binds to the test compound.   
     
     
         18 . The method of  claim 17 , wherein the binding of the test compound to the polypeptide is detected by a method selected from the group consisting of:
 a) detection of binding by direct detecting of test compound/polypeptide binding;   b) detection of binding using a competition binding assay;   c) detection of binding using an assay for GAP mediated nucleotide exchange.   
     
     
         19 . A method for modulating the activity of a polypeptide of  claim 6  comprising contacting a polypeptide or a cell expressing a polypeptide of  claim 6  with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide. 
     
     
         20 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 6 , comprising:
 a) contacting a polypeptide of  claim 6  with a test compound; and   b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound that modulates the activity of the polypeptide.