PNPLA3
Function
Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and precursor for both triglycerides and glycerophospholipids. Does not esterify other lysophospholipids. Acyl donors are long chain (at least C16) fatty acyl-CoAs: arachidonoyl-CoA, linoleoyl-CoA, oleoyl-CoA and at a lesser extent palmitoyl-CoA (PubMed:22560221). Additionally possesses low triacylglycerol lipase and CoA-independent acylglycerol transacylase activities and thus may play a role in acyl-chain remodeling of triglycerides (PubMed:15364929, PubMed:20034933, PubMed:22560221). In vitro may express hydrolytic activity against glycerolipids triacylglycerol, diacylglycerol and monoacylglycerol, with a strong preference for oleic acid as the acyl moiety (PubMed:21878620). However, the triacylglycerol hydrolase activity is controversial and may be very low (PubMed:22560221). Possesses phospholipase A2 activity (PubMed:15364929).
Involvement in disease
Non-alcoholic fatty liver disease 1
NAFLD1
A condition characterized by accumulation of triglycerides in the liver. It is associated with adverse metabolic consequences, including insulin resistance and dyslipidemia. In a subset of individuals, hepatic steatosis promotes an inflammatory response in the liver, referred to as steatohepatitis, which can progress to cirrhosis and liver cancer. NAFLD is the most common form of liver disease in Western countries.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Pathway
Phospholipid metabolism.
Glycerolipid metabolism.
Cellular localization
- Membrane
- Single-pass type II membrane protein
- Lipid droplet
Alternative names
ADPN, C22orf20, PNPLA3, 1-acylglycerol-3-phosphate O-acyltransferase PNPLA3, Acylglycerol transacylase, Adiponutrin, Calcium-independent phospholipase A2-epsilon, Lysophosphatidic acid acyltransferase, Patatin-like phospholipase domain-containing protein 3, iPLA2-epsilon