Pnpla2 phospho S406
Developmental stage
Increased expression when preadipocytes are induced to differentiate to adipocytes. Not detected in proliferating or confluent preadipocytes.
Function
Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets (PubMed:15337759, PubMed:15550674, PubMed:16150821, PubMed:16675698, PubMed:16679289, PubMed:17074755, PubMed:17114792, PubMed:23066022). Exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone and acts coordinately with LIPE/HLS and DGAT2 within the lipolytic cascade (PubMed:23066022). Also possesses acylglycerol transacylase and phospholipase A2 activities (By similarity). Transfers fatty acid from triglyceride to retinol, hydrolyzes retinylesters, and generates 1,3-diacylglycerol from triglycerides (By similarity). Regulates adiposome size and may be involved in the degradation of adiposomes (By similarity). Catalyzes the formation of an ester bond between hydroxy fatty acids and fatty acids derived from triglycerides or diglycerides to generate fatty acid esters of hydroxy fatty acids (FAHFAs) in adipocytes (PubMed:35676490). Acts antagonistically with LDAH in regulation of cellular lipid stores (By similarity). Inhibits LDAH-stimulated lipid droplet fusion (By similarity). May play an important role in energy homeostasis (PubMed:16675698). May play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion (PubMed:15337759).
Pathway
Glycerolipid metabolism; triacylglycerol degradation.
Post-translational modifications
Phosphorylation at Ser-406 by PKA is increased during fasting and moderate intensity exercise, and moderately increases lipolytic activity.
Ubiquitinated by PEX2 in response to reactive oxygen species (ROS), leading to its degradation (By similarity). Ubiquitination is stimulated by LDAH (By similarity).
Tissue Specificity
Expressed at high levels in white and brown adipose tissue, and to a lesser degree in testis and cardiac muscle. Barely detected in liver, spleen, thymus, kidney, skeletal muscle, and brain. Among the white adipose depots, gonadal fat showed the highest level of expression compared with inguinal and renal white adipose tissues.
Cellular localization
- Lipid droplet
- Cell membrane
- Multi-pass membrane protein
- Cytoplasm
Alternative names
Atgl, Pnpla2, Patatin-like phospholipase domain-containing protein 2, Adipose triglyceride lipase, Calcium-independent phospholipase A2-zeta, Desnutrin, iPLA2-zeta