Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members.
Studies involving the cloning and disruption of the gene for acyl-CoA:diacylglycerol acyltransferase (DGAT) have shown that alternative mechanisms exist for triglyceride synthesis. In this study, we cloned and characterized a second mammalian DGAT, DGAT2, which was identified by its homology to a DGAT in the fungus Mortierella rammaniana. DGAT2 is a member of a gene family that has no homology with DGAT1 and includes several mouse and human homologues that are candidates for additional DGAT genes. The expression of DGAT2 in insect cells stimulated triglyceride synthesis 6-fold in assays with cellular membranes, and DGAT2 activity was dependent on the presence of fatty acyl-CoA and diacylglycerol, indicating that this protein is a DGAT. Activity was not observed for acyl acceptors other than diacylglycerol. DGAT2 activity was inhibited by a high concentration (100 mm) of MgCl(2) in an in vitro assay, a characteristic that distinguishes DGAT2 from DGAT1. DGAT2 is expressed in many tissues with high expression levels in the liver and white adipose tissue, suggesting that it may play a significant role in mammalian triglyceride metabolism.
Cases
S
S
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94143, USA.
Stone
S J
SJ
Zhou
P
P
Yen
E
E
Tow
B
B
Lardizabal
K D
KD
Voelker
T
T
Farese
R V
RV
D016475:3T3 Cells; D000217:Acyltransferases / Q000737:chemistry / Q000145:classification* / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D051048:Diacylglycerol O-Acyltransferase; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D007313:Insecta; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D015636:Magnesium Chloride / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D020094:Mortierella / Q000201:enzymology; D005810:Multigene Family; D010802:Phylogeny; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution; D014280:Triglycerides / Q000096:biosynthesis
D018076:DNA, Complementary; D014280:Triglycerides; D015636:Magnesium Chloride; D000217:Acyltransferases; C494885:DGAT2 protein, human; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase