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FUNCTION Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets (PubMed:15364929, PubMed:15550674, PubMed:16150821, PubMed:16239926, PubMed:17603008, PubMed:34903883). 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 (By similarity). Also possesses acylglycerol transacylase and phospholipase A2 activities (PubMed:15364929, PubMed:17032652, PubMed:17603008). Transfers fatty acid from triglyceride to retinol, hydrolyzes retinylesters, and generates 1,3-diacylglycerol from triglycerides (PubMed:17603008). Regulates adiposome size and may be involved in the degradation of adiposomes (PubMed:16239926). 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 (PubMed:28578400). Inhibits LDAH-stimulated lipid droplet fusion (PubMed:28578400). May play an important role in energy homeostasis (By similarity). 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 (By similarity).CATALYTIC ACTIVITY a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+)CATALYTIC ACTIVITY a triacylglycerol + H2O = a 1,2-diacylglycerol + a fatty acid + H(+)CATALYTIC ACTIVITY a triacylglycerol + H2O = a 1,3-diacylglycerol + a fatty acid + H(+)CATALYTIC ACTIVITY a triacyl-sn-glycerol + H2O = a 1,3-diacyl-sn-glycerol + a fatty acid + H(+)CATALYTIC ACTIVITY a triacyl-sn-glycerol + H2O = a 2,3-diacyl-sn-glycerol + a fatty acid + H(+)CATALYTIC ACTIVITY a 1-acylglycerol + a 1,3-diacylglycerol = a triacylglycerol + glycerolCATALYTIC ACTIVITY a 1-acylglycerol + a 1,2-diacylglycerol = a triacylglycerol + glycerolCATALYTIC ACTIVITY 2 a 1-acylglycerol = a 1,2-diacylglycerol + glycerolCATALYTIC ACTIVITY a triacylglycerol + all-trans-retinol = an all-trans-retinyl ester + a diacylglycerolCATALYTIC ACTIVITY 1,2-di-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoate + H(+) = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2OCATALYTIC ACTIVITY 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = 1,3-di-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoate + H(+)CATALYTIC ACTIVITY 1-(9Z-octadecenoyl)-glycerol + 1,3-di-(9Z-octadecenoyl)-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerolCATALYTIC ACTIVITY 1-(9Z-octadecenoyl)-glycerol + 1,2-di-(9Z-octadecenoyl)-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerolCATALYTIC ACTIVITY 2 1-(9Z-octadecenoyl)-glycerol = 1,2-di-(9Z-octadecenoyl)-glycerol + glycerolCATALYTIC ACTIVITY 1,2,3-tri-(9Z-octadecenoyl)-glycerol + all-trans-retinol = all-trans-retinyl 9Z-octadecenoate + di-(9Z)-octadecenoylglycerolCATALYTIC ACTIVITY 1,2,3-tri-(9Z)-hexadecenoylglycerol + H2O = 1,3-di-(9Z)-hexadecenoylglycerol + (9Z)-hexadecenoate + H(+)CATALYTIC ACTIVITY 1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + H2O = 1,3-di-(9Z,12Z)-octadecadienoylglycerol + (9Z,12Z)-octadecadienoate + H(+)CATALYTIC ACTIVITY 1,2,3-tri-(9Z,12Z,15Z)-octadecatrienoylglycerol + H2O = 1,3-di-(9Z,12Z,15Z)-octadecatrienoylglycerol + (9Z,12Z,15Z)-octadecatrienoate + H(+)CATALYTIC ACTIVITY 1,3-di-(9Z)-octadecenoyl-2-hexadecanoylglycerol + H2O = 1,3-di-(9Z-octadecenoyl)-glycerol + hexadecanoate + H(+)CATALYTIC ACTIVITY 1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + H2O = 1-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + (9Z)-octadecenoate + H(+)CATALYTIC ACTIVITY 1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = 1-hexadecanoyl-3-(9Z)-octadecenoyl-sn-glycerol + (9Z)-octadecenoate + H(+)CATALYTIC ACTIVITY 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = 2,3-di-(9Z)-octadecenoyl-sn-glycerol + (9Z)-octadecenoate + H(+)CATALYTIC ACTIVITY 1,2,3-tri-(9Z)-hexadecenoylglycerol + H2O = 2,3-di-(9Z)-hexadecenoyl-sn-glycerol + (9Z)-hexadecenoate + H(+)CATALYTIC ACTIVITY 1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + H2O = 2,3-di-(9Z,12Z)-octadecadienoyl-sn-glycerol + (9Z,12Z)-octadecadienoate + H(+)CATALYTIC ACTIVITY 1,2,3-tri-(9Z,12Z,15Z)-octadecatrienoylglycerol + H2O = 2,3-di-(9Z,12Z,15Z)-octadecatrienoyl-sn-glycerol + (9Z,12Z,15Z)-octadecatrienoate + H(+)CATALYTIC ACTIVITY 1,3-di-(9Z)-octadecenoyl-2-hexadecanoylglycerol + H2O = 2-hexadecanoyl-3-(9Z)-octadecenoyl-sn-glycerol + (9Z)-octadecenoate + H(+)CATALYTIC ACTIVITY 1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = 2,3-di-(9Z)-octadecenoyl-sn-glycerol + hexadecanoate + H(+)CATALYTIC ACTIVITY 1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + H2O = 2-(9Z-octadecenoyl)-3-hexadecanoyl-sn-glycerol + (9Z)-octadecenoate + H(+)CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+)CATALYTIC ACTIVITY 1,2,3-tri-(9Z-octadecenoyl)-glycerol + 9-hydroxy-octadecanoate = 9-(9Z-octadecenoyloxy)-octadecanoate + 2,3-di-(9Z)-octadecenoyl-sn-glycerolCATALYTIC ACTIVITY 1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + 9-hydroxy-octadecanoate = 9-hexadecanoyloxy-octadecanoate + 2,3-di-(9Z)-octadecenoyl-sn-glycerolCATALYTIC ACTIVITY 1,2,3-tri-(10Z)-heptadecenoylglycerol + 9-hydroxy-octadecanoate = 2,3-di-(10Z-heptadecenoyl)-sn-glycerol + 9-(10Z-heptadecenoyloxy)-octadecanoateCATALYTIC ACTIVITY 1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + 9-hydroxy-octadecanoate = 2,3-di-(9Z,12Z)-octadecadienoyl-sn-glycerol + 9-(9Z,12Z-octadecadienoyloxy)-octadecanoateCATALYTIC ACTIVITY 1,2,3-tri-(9Z)-hexadecenoylglycerol + 9-hydroxy-octadecanoate = 2,3-di-(9Z)-hexadecenoyl-sn-glycerol + 9-(9Z-hexadecenoyloxy)-octadecanoateCATALYTIC ACTIVITY 9-hydroxy-octadecanoate + 1,2-di-(9Z-octadecenoyl)-sn-glycerol = 9-(9Z-octadecenoyloxy)-octadecanoate + 2-(9Z-octadecenoyl)-glycerolCATALYTIC ACTIVITY 1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + 9-hydroxy-octadecanoate = 1-hexadecanoyl-3-(9Z)-octadecenoyl-sn-glycerol + 9-(9Z-octadecenoyloxy)-octadecanoateACTIVITY REGULATION The triglyceride lipase activity is inhibited by BEL ((E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one), a suicide substrate inhibitor (PubMed:17032652). No differences in the acylglycerol transacylase was detected in the presence or absence of ATP (PubMed:15364929).BIOPHYSICOCHEMICAL PROPERTIES Optimum pH is 7.5 with (1,2-dilinoleoyl)-phosphatidylcholine as substrate.PATHWAY Glycerolipid metabolism; triacylglycerol degradation.SUBUNIT Interacts with ABHD5; this association stimulates PNPLA2 triglyceride hydrolase activity (By similarity). Interacts with SERPINF1; this interaction stimulates the phospholipase A2 activity of PNPLA2 (PubMed:17032652). Despite a colocalization in lipid droplets, it probably does not interact with PLIN (By similarity). Interacts with PLIN5; prevents interaction with ABHD5 (By similarity). Interacts with FAF2 (PubMed:23297223).SUBCELLULAR LOCATION Highest expression in adipose tissue. Also detected in heart, skeletal muscle, and portions of the gastrointestinal tract. Detected in normal retina and retinoblastoma cells. Detected in retinal pigment epithelium and, at lower intensity, in the inner segments of photoreceptors and in the ganglion cell layer of the neural retina (at protein level).DEVELOPMENTAL STAGE Induced during differentiation of primary preadipocytes to adipocytes. Expression increased from fetal to adult in retinal pigment epithelium.PTM Phosphorylation at Ser-404 by PKA is increased during fasting and moderate intensity exercise, and moderately increases lipolytic activity (By similarity). Phosphorylation at Ser-404 is increased upon beta-adrenergic stimulation (PubMed:22733971).PTM Ubiquitinated by PEX2 in response to reactive oxygen species (ROS), leading to its degradation (PubMed:34903883). Ubiquitination is stimulated by LDAH (PubMed:28578400).POLYMORPHISM Genetic variations in PNPLA2 may influence plasma free fatty acids and triglycerides levels, and fasting glucose concentrations.DISEASE Genetic variations in PNPLA2 may be associated with risk of diabetes mellitus type 2.DISEASE The disease is caused by variants affecting the gene represented in this entry.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.
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