Polynucleotide encoding a novel acyl coenzyme a, monoacylglycerol acyltransferase-3 (mgat3), and uses thereof

Abstract

The present invention provides novel polynucleotides encoding MGAT3 polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel MGAT3 polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides, such as obesity. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

1 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) a polypeptide fragment of SEQ ID NO:2 encoded by at least one of ATCC Deposit No: PTA-4454 or PTA-4803;    (b) a polypeptide fragment of SEQ ID NO:2 encoded by at least one of ATCC Deposit No: PTA-4454 or PTA-4803, having MGAT activity;    (c) a polypeptide domain of SEQ ID NO:2 encoded by at least one of ATCC Deposit No: PTA-4454 or PTA-4803;    (d) a polypeptide epitope of SEQ ID NO:2 or the encoded sequence encoded by at least one of ATCC Deposit No: PTA-4454 or PTA-4803;    (e) a full length protein of SEQ ID NO:2 encoded by at least one of ATCC Deposit No: PTA-4454 or PTA-4803;    (f) a polypeptide comprising amino acids 2 to 341 of SEQ ID NO:2, wherein said amino acids 2 to 341 comprises a polypeptide of SEQ ID NO:2 minus the start methionine; and    (g) a polypeptide comprising amino acids 1 to 341 of SEQ ID NO:2.    
   
   
       2 . The isolated polypeptide of  claim 1 , wherein the full length protein comprises sequential amino acid deletions from either the C-terminus or the N-terminus.  
   
   
       3 . An isolated antibody that binds specifically to said isolated polypeptide of  claim 1 .  
   
   
       4 . A recombinant host cell that expresses said isolated polypeptide of  claim 1 .  
   
   
       5 . A method of making an isolated polypeptide comprising: 
 (a) culturing said recombinant host cell of  claim 4  under conditions such that said polypeptide is expressed; and    (b) recovering said polypeptide.    
   
   
       6 . The polypeptide produced by  claim 5 .  
   
   
       7 . A method for preventing, treating, or ameliorating a medical condition, comprising the step of administering to a mammalian subject a therapeutically effective amount of said polypeptide of  claim 1 , or a modulator thereof.  
   
   
       8 . A method of  claim 7 , wherein said medical condition is related to aberrant MGAT3 activity.  
   
   
       9 . A method of  claim 7 , wherein said medical condition is selected from the group consisting of obesity and a gastrointestinal disorder.  
   
   
       10 . A method of  claim 12 , wherein said gastrointestinal disorder is Crohn's disease.  
   
   
       11 . A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising: 
 (a) determining the presence or absence of a mutation in a polypeptide of  claim 1;  and    (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or absence of said mutation.    
   
   
       12 . A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising: 
 (a) determining the presence or amount of expression of said polypeptide of  claim 1  in a gastrointestinal tissue sample; and    (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of said polypeptide.    
   
   
       13 . A method of treating Crohn's disease comprising administering to a patient in need thereof an MGAT3 polypeptide or a modulator thereof.