Diacylglycerol o-acyltransferase 2alpha (DGAT2alpha)

Abstract

Nucleic acid compositions encoding mammalian DGAT2α polypeptide products with diglyceride acyltransferase activity, as well as the mammalian DGAT2α polypeptide products encoded thereby and methods for producing the same, are provided. The subject DGAT2α polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications, as well as in treatment therapies and in the production of triacylglycerols.

What is claimed is:  
     
         1 . A mammalian polynucleotide present in other than its natural environment encoding a DGAT2α product.  
     
     
         2 . The polynucleotide according to  claim 2 , wherein said polynucleotide comprises a sequence substantially similar or identical to a sequence selected from the group consisting of SEQ ID NO:01 and SEQ ID NO: 03.  
     
     
         3 . A fragment of a polynucleotide according to  claim 1 .  
     
     
         4 . A mammalian DGAT2α polypeptide present in other than its naturally occurring environment.  
     
     
         5 . The polypeptide according to  claim 4 , wherein said polypeptide has an amino acid sequence that is substantially the same as or identical to a sequence selected from the group consisting of SEQ ID NO:02 and SEQ ID NO:04.  
     
     
         6 . Substantially pure mammalian DGAT2α 
     
     
         7 . Isolated mammalian DGAT2α.  
     
     
         8 . A fragment of a polypeptide according to  claim 4 .  
     
     
         9 . An expression cassette comprising a transcriptional initiation region functional in an expression host, a polynucleotide having a nucleotide sequence found in the nucleic acid according to  claim 1  under the transcriptional regulation of said transcriptional initiation region, and a transcriptional termination region functional in said expression host.  
     
     
         10 . A cell comprising an expression cassette according to  claim 9  as part of an extrachromosomal element or integrated into the genome of a host cell as a result of introduction of said expression cassette into said host cell.  
     
     
         11 . The cellular progeny of the cell according to  claim 10 .  
     
     
         12 . A method of producing a DGAT2α polypeptide, said method comprising: 
 growing a cell according to  claim 10 , whereby said polypeptide is expressed; and  
 isolating said polypeptide substantially free of other proteins.  
 
     
     
         13 . A monoclonal antibody binding specifically to a DGAT2α polypeptide.  
     
     
         14 . The monoclonal antibody according to  claim 13 , wherein said antibody inhibits diglyceride acyltransferase activity of said polypeptide.  
     
     
         15 . The monoclonal antibody according to  claim 13 , wherein said antibody is a humanized antibody.  
     
     
         16 . A method for inhibiting the activity of a DGAT2α protein, said method comprising: 
 contacting said DGAT2α protein with an agent that inhibits the activity of said DGAT2α protein.  
 
     
     
         17 . The method according to  claim 16 , wherein said agent is a small molecule.  
     
     
         18 . The method according to  claim 16 , wherein said agent is an antibody.  
     
     
         19 . The method according to  claim 18 , wherein said agent is a monoclonal antibody.  
     
     
         20 . A method of modulating a symptom in a mammalian host of a disease condition associated with DGAT2α activity, said method comprising: 
 administering to said host a pharmaceutical composition comprising an effective amount of an active agent that modulates said DGAT2α activity in said host.  
 
     
     
         21 . The method according to  claim 20 , wherein said symptom is hypertriglycemia.  
     
     
         22 . The method according to  claim 20 , wherein said symptom is obesity  
     
     
         23 . A method of producing a triacylglycerol, said method comprising: 
 contacting a diacylglyercol and fatty acyl CoA with a DGAT2α polypeptide under conditions sufficient to said triacylglycerol to be produced.