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Description

1-acylglycerol-3-phosphate O-acyltransferase Pnpla3 ( UniProt: Q91WW7, also known s EC:2.3.1.51, Acylglycerol transacylase, Adiponutrin, ADPN, Calcium-independent phospholipase A2-epsilon, iPLA2-epsilon, Lysophosphatidic acid acyltransferase, Patatin-like phospholipase domain-containing protein 3) is encoded by the Pnpla3 (also known as Adpn) gene (Gene ID: 116939) in murine species. PNPLA3 is a single-pass membrane glycoprotein with a cytoplasmic domain (aa 1-42), a transmembrane domain (aa 43-63), and a lumenal domain (aa 64-413). Its expression is restricted to adipose tissue and is also observed in liver in response to high-sucrose diet. It is found in hepatic lipid droplets. PNPLA3 catalyzes coenzyme A-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), which is an important metabolic intermediate and precursor for both triglycerides and glycerophospholipids. For its activity, acyl donors are long chain (at least C16) fatty acyl-CoAs. PNPLA3 also exhibits low triacylglycerol lipase and CoA-independent acylglycerol transacylase activities. Mutations in Pnpla3 gene have been linked to increased risk of hepatic steatosis. Catalytically defective forms of PNPLA3 with I148M or S47A mutations are reported to cause increased hepatic triglyceride accumulation of triglycerides (TG) in sucrose fed mice. PNPLA3 knockdown is reported to reduce TG content in mice overexpressing I148 form. (Ref.: BasuRay, S., et al. (2019). Proc. Natl. Acad. Sci. USA. 116(19), 9521-9526, BasuRay, S., et al. (2017). Hepatology. 66(4), 1111-1124, Kumari, M., et al. (2012). Cell Metab. 15(5), 691-702).