21612, 21615, 21620, 21676, 33756, novel human alcohol dehydrogenases

Abstract

The present invention relates to newly identified human ADHs belonging to the superfamily of mammalian alcohol dehydrogenases. The invention also relates to polynucleotides encoding the ADHs. The invention further relates to methods using the ADH polypeptides and polynucleotides as a target for diagnosis and treatment in ADH-mediated or -related disorders. The invention further relates to drug-screening methods using the ADH polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the ADH polypeptides and polynucleotides. The invention further relates to procedures for producing the ADH polypeptides and polynucleotides.

That which is claimed:  
     
         1 . An isolated nucleic acid molecule selected from the group consisting of: 
 a) a nucleic acid molecule having a nucleotide sequence that is at least 60% identical to the nucleotide sequence of SEQ ID NO:2, 4, 6, 8, or 10, or the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit Numbers PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; or a complement thereof;    b) a nucleic acid molecule having at least 15 contiguous nucleotides of the nucleotide sequence of SEQ ID NO:2, 4, 6, 8, or 10, or at least 15 contiguous nucleotides of the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit Numbers PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; or a complement thereof;    c) a nucleic acid molecule having a nucleotide sequence that encodes a polypeptide having the amino acid sequence of SEQ ID NO:1, 3, 5, 7, or 9, or an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit Numbers PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; or a complement thereof;    d) a nucleic acid molecule having a nucleotide sequence that encodes a fragment of a polypeptide having the amino acid sequence of SEQ ID NO:1, 3, 5, 7, or 9, or an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit Numbers PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; wherein the fragment has at least 12 contiguous amino acids of SEQ ID NO:1, 3, 5, 7, or 9, or an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; or a complement thereof; and    e) a nucleic acid molecule having a nucleotide sequence that encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:1, 3, 5, 7, or 9, or an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit Numbers PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO:2, 4, 6, 8, or 10, or a complement thereof, under stringent conditions.    
     
     
         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 having the nucleotide sequence of SEQ ID NO:2, 4, 6, 8, or 10, the cDNA insert of any one the plasmids deposited with ATCC as Patent Deposit PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; or a complement thereof; and    b) a nucleic acid molecule encoding a polypeptide having the amino acid sequence of SEQ ID NO:1, 3, 5, 7, or 9, or an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; or a complement thereof    
     
     
         3 . The nucleic acid molecule of  claim 1 , further having vector nucleic acid sequences.  
     
     
         4 . The nucleic acid molecule of  claim 1 , further having nucleic acid sequences encoding a heterologous polypeptide.  
     
     
         5 . A host cell having the nucleic acid molecule of  claim 1 .  
     
     
         6 . The host cell of  claim 5 , wherein said host cell is mammalian.  
     
     
         7 . A nonhuman mammalian host cell having the nucleic acid molecule of  claim 1 .  
     
     
         8 . An isolated polypeptide selected from the group consisting of 
 a) a fragment of a polypeptide, wherein said fragment has at least 12 contiguous amino acids of SEQ ID NO:1, 3, 5, 7, or 9, or at least 12 contiguous amino acids of an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit Numbers PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813;    b) a naturally occurring allelic variant of a polypeptide having the amino acid sequence of SEQ ID NO:1, 3, 5, 7, or 9, or an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit Numbers PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule having the nucleotide sequence set forth in SEQ ID NO:2, 4, 6, 8, or 19, or a complement thereof under stringent conditions; and    c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence that is at least 60% identical to a nucleic acid molecule having the nucleotide sequence set forth in SEQ ID NO:2, 4, 6, 8, or 10, or a complement thereof.    
     
     
         9 . The isolated polypeptide of  claim 8 , wherein said polypeptide has the amino acid sequence of SEQ ID NO:1, 3, 5, 7, or 9, or an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit Numbers PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813;  
     
     
         10 . The polypeptide of  claim 8 , further comprising heterologous amino acid sequences.  
     
     
         11 . An antibody which binds to a polypeptide of  claim 8 .  
     
     
         12 . A method for producing a polypeptide selected from the group consisting of: 
 a) a polypeptide having the amino acid sequence of SEQ ID NO:1, 3, 5, 7, or 9; or an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813;    b) a polypeptide having a fragment, wherein said fragment has at least 12 contiguous amino acids of SEQ ID NO:1, 3, 5, 7, or 9, or at least 12 contiguous amino acids of an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit Numbers PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; and    c) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:1, 3, 5, 7, or 9, or an amino acid sequence encoded by the cDNA insert of any one of the plasmids deposited with ATCC as Patent Deposit Numbers PTA-2012, PTA-2170, PTA-2171, PTA-2812, or PTA-2813; wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:2, 4, 6, 8, or 10, or a complement thereof under stringent conditions;    said method comprising culturing the host cell of  claim 5  under conditions in which the nucleic acid molecule is expressed.    
     
     
         13 . The method of  claim 12 , wherein said polypeptide has the amino acid sequence shown in SEQ ID NO:1, 3, 5, 7, or 9.  
     
     
         14 . A method for detecting the presence of a polypeptide of  claim 8  in a sample, said method having the steps of: 
 a) contacting the sample with a compound that selectively binds to a polypeptide of claim  8 ; and  
 b) determining whether the compound binds to the polypeptide in the sample.  
 
     
     
         15 . The method of  claim 14 , wherein the compound that binds to the polypeptide is an antibody.  
     
     
         16 . A kit having a compound that selectively binds to a polypeptide of  claim 8  and instructions for use.  
     
     
         17 . A method for detecting the presence of a nucleic acid molecule of  claim 1  in a sample, said method having the steps of: 
 a) contacting the sample with a nucleic acid probe or primer that selectively hybridizes to a nucleic acid molecule of claim  1 ; and  
 b) determining whether the nucleic acid probe or primer binds to the nucleic acid molecule in the sample.  
 
     
     
         18 . The method of  claim 17 , wherein the sample contains mRNA molecules and is contacted with a nucleic acid probe.  
     
     
         19 . A kit having a compound that selectively hybridizes to a nucleic acid molecule of  claim 1  and instructions for use.  
     
     
         20 . A method for identifying a compound that binds to a polypeptide of  claim 8 , said method having the steps of: 
 a) contacting a polypeptide of  claim 8 , or a cell expressing a polypeptide of  claim 8  with a test compound; and    b) determining whether the polypeptide binds to the test compound.    
     
     
         21 . The method of  claim 20 , 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 alcohol dehydrogenase activity.    
     
     
         22 . A method for modulating the activity of a polypeptide of  claim 8 , said method comprising contacting a polypeptide of  claim 8  or a cell expressing a polypeptide of  claim 8  with a compound that binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.  
     
     
         23 . A method for identifying a compound that modulates the activity of a polypeptide of  claim 8 , said method having the steps of: 
 a) contacting a polypeptide of  claim 8  with a test compound; and    b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound which modulates the activity of the polypeptide.    
     
     
         24 . A method for identifying an agent that modulates the level of expression of a nucleic acid molecule of  claim 1  in a cell, said method comprising contacting said agent with the cell expressing said nucleic acid molecule such that said level of expression of said nucleic acid molecule can be modulated in said cell by said agent and measuring said level of expression of said nucleic acid molecule.  
     
     
         25 . A method for modulating the level of expression of a nucleic acid molecule of  claim 1 , said method comprising contacting said nucleic acid molecule with an agent under conditions that allow the agent to modulate the level of expression of the nucleic acid molecule.  
     
     
         26 . A pharmaceutical composition containing at least one of the polypeptides in  claim 8  in a pharmaceutically acceptable carrier.