ID PLPL2_MOUSE Reviewed; 486 AA. AC Q8BJ56; O89080; Q05BJ0; Q3UD97; Q643S0; Q6P234; Q9D1Q9; Q9DCF6; DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 27-MAR-2024, entry version 149. DE RecName: Full=Patatin-like phospholipase domain-containing protein 2 {ECO:0000305}; DE EC=3.1.1.3 {ECO:0000269|PubMed:15337759, ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:16150821, ECO:0000269|PubMed:16675698, ECO:0000269|PubMed:16679289, ECO:0000269|PubMed:17074755, ECO:0000269|PubMed:23066022}; DE AltName: Full=Adipose triglyceride lipase; DE AltName: Full=Calcium-independent phospholipase A2-zeta {ECO:0000250|UniProtKB:Q96AD5}; DE Short=iPLA2-zeta {ECO:0000250|UniProtKB:Q96AD5}; DE EC=3.1.1.4 {ECO:0000250|UniProtKB:Q96AD5}; DE AltName: Full=Desnutrin; GN Name=Pnpla2 {ECO:0000312|MGI:MGI:1914103}; Synonyms=Atgl; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, AND CATALYTIC ACTIVITY. RC STRAIN=C57BL/6J; TISSUE=White adipose tissue; RX PubMed=15337759; DOI=10.1074/jbc.m403855200; RA Villena J.A., Roy S., Sarkadi-Nagy E., Kim K.-H., Sul H.S.; RT "Desnutrin, an adipocyte gene encoding a novel patatin domain-containing RT protein, is induced by fasting and glucocorticoids: ectopic expression of RT desnutrin increases triglyceride hydrolysis."; RL J. Biol. Chem. 279:47066-47075(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ACTIVITY REGULATION, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, RP PHOSPHORYLATION, AND CATALYTIC ACTIVITY. RC STRAIN=C57BL/6J; RX PubMed=15550674; DOI=10.1126/science.1100747; RA Zimmermann R., Strauss J.G., Haemmerle G., Schoiswohl G., RA Birner-Gruenberger R., Riederer M., Lass A., Neuberger G., Eisenhaber F., RA Hermetter A., Zechner R.; RT "Fat mobilization in adipose tissue is promoted by adipose triglyceride RT lipase."; RL Science 306:1383-1386(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION. RC STRAIN=C57BL/6J; RX PubMed=16705060; DOI=10.1152/ajpendo.00317.2005; RA Kim J.Y., Tillison K., Lee J.-H., Rearick D.A., Smas C.M.; RT "The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by RT insulin and TNF-alpha in 3T3-L1 adipocytes and is a target for RT transactivation by PPARgamma."; RL Am. J. Physiol. 291:E115-E127(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Kidney, and Testis; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC STRAIN=FVB/N; TISSUE=Trophoblast stem cell; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 296-473. RC STRAIN=BALB/cJ; TISSUE=Spleen; RX PubMed=9798653; DOI=10.1016/s0161-5890(98)00031-5; RA Chu C.C., Paul W.E.; RT "Expressed genes in interleukin-4 treated B cells identified by cDNA RT representational difference analysis."; RL Mol. Immunol. 35:487-502(1998). RN [7] RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION. RX PubMed=16150821; DOI=10.1194/jlr.m500290-jlr200; RA Lake A.C., Sun Y., Li J.-L., Kim J.E., Johnson J.W., Li D., Revett T., RA Shih H.H., Liu W., Paulsen J.E., Gimeno R.E.; RT "Expression, regulation, and triglyceride hydrolase activity of Adiponutrin RT family members."; RL J. Lipid Res. 46:2477-2487(2005). RN [8] RP INDUCTION. RX PubMed=16009485; DOI=10.1016/j.mce.2005.06.002; RA Kralisch S., Klein J., Lossner U., Bluher M., Paschke R., Stumvoll M., RA Fasshauer M.; RT "Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride RT lipase in 3T3-L1 adipocytes."; RL Mol. Cell. Endocrinol. 240:43-49(2005). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ABHD5, AND MUTAGENESIS OF RP SER-47. RX PubMed=16679289; DOI=10.1016/j.cmet.2006.03.005; RA Lass A., Zimmermann R., Haemmerle G., Riederer M., Schoiswohl G., RA Schweiger M., Kienesberger P., Strauss J.G., Gorkiewicz G., Zechner R.; RT "Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is RT activated by CGI-58 and defective in Chanarin-Dorfman Syndrome."; RL Cell Metab. 3:309-319(2006). RN [10] RP INDUCTION. RX PubMed=16380488; DOI=10.2337/diabetes.55.1.148; RA Kershaw E.E., Hamm J.K., Verhagen L.A.W., Peroni O., Katic M., Flier J.S.; RT "Adipose triglyceride lipase: function, regulation by insulin, and RT comparison with adiponutrin."; RL Diabetes 55:148-157(2006). RN [11] RP FUNCTION, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY. RX PubMed=17074755; DOI=10.1074/jbc.m608048200; RA Schweiger M., Schreiber R., Haemmerle G., Lass A., Fledelius C., RA Jacobsen P., Tornqvist H., Zechner R., Zimmermann R.; RT "Adipose triglyceride lipase and hormone-sensitive lipase are the major RT enzymes in adipose tissue triacylglycerol catabolism."; RL J. Biol. Chem. 281:40236-40241(2006). RN [12] RP FUNCTION, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY. RX PubMed=16675698; DOI=10.1126/science.1123965; RA Haemmerle G., Lass A., Zimmermann R., Gorkiewicz G., Meyer C., Rozman J., RA Heldmaier G., Maier R., Theussl C., Eder S., Kratky D., Wagner E.F., RA Klingenspor M., Hoefler G., Zechner R.; RT "Defective lipolysis and altered energy metabolism in mice lacking adipose RT triglyceride lipase."; RL Science 312:734-737(2006). RN [13] RP ACTIVITY REGULATION, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=17114792; DOI=10.1074/jbc.m605770200; RA Miyoshi H., Perfield J.W. II, Souza S.C., Shen W.-J., Zhang H.-H., RA Stancheva Z.S., Kraemer F.B., Obin M.S., Greenberg A.S.; RT "Control of adipose triglyceride lipase action by serine 517 of perilipin A RT globally regulates protein kinase A-stimulated lipolysis in adipocytes."; RL J. Biol. Chem. 282:996-1002(2007). RN [14] RP INTERACTION WITH ABHD5, AND LACK OF INTERACTION WITH PLIN. RX PubMed=17189257; DOI=10.1074/jbc.m610580200; RA Granneman J.G., Moore H.-P.H., Granneman R.L., Greenberg A.S., Obin M.S., RA Zhu Z.; RT "Analysis of lipolytic protein trafficking and interactions in RT adipocytes."; RL J. Biol. Chem. 282:5726-5735(2007). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-406 AND SER-430, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [16] RP INTERACTION WITH PLIN5, AND EXCLUSION OF INTERACTION WITH ABHD5. RX PubMed=21148142; DOI=10.1074/jbc.m110.180711; RA Granneman J.G., Moore H.P., Mottillo E.P., Zhu Z., Zhou L.; RT "Interactions of perilipin-5 (Plin5) with adipose triglyceride lipase."; RL J. Biol. Chem. 286:5126-5135(2011). RN [17] RP INTERACTION WITH PLIN5. RX PubMed=21393244; DOI=10.1074/jbc.m110.207779; RA Wang H., Bell M., Sreenivasan U., Sreenevasan U., Hu H., Liu J., Dalen K., RA Londos C., Yamaguchi T., Rizzo M.A., Coleman R., Gong D., Brasaemle D., RA Sztalryd C.; RT "Unique regulation of adipose triglyceride lipase (ATGL) by perilipin 5, a RT lipid droplet-associated protein."; RL J. Biol. Chem. 286:15707-15715(2011). RN [18] RP PHOSPHORYLATION AT SER-374; SER-396; SER-406; SER-430 AND SER-468, AND RP MUTAGENESIS OF SER-396 AND SER-406. RX PubMed=22733971; DOI=10.1210/en.2012-1127; RA Pagnon J., Matzaris M., Stark R., Meex R.C., Macaulay S.L., Brown W., RA O'Brien P.E., Tiganis T., Watt M.J.; RT "Identification and functional characterization of protein kinase A RT phosphorylation sites in the major lipolytic protein, adipose triglyceride RT lipase."; RL Endocrinology 153:4278-4289(2012). RN [19] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23066022; DOI=10.1074/jbc.m112.400416; RA Eichmann T.O., Kumari M., Haas J.T., Farese R.V. Jr., Zimmermann R., RA Lass A., Zechner R.; RT "Studies on the substrate and stereo/regioselectivity of adipose RT triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O- RT acyltransferases."; RL J. Biol. Chem. 287:41446-41457(2012). RN [20] RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE. RX PubMed=35676490; DOI=10.1038/s41586-022-04787-x; RA Patel R., Santoro A., Hofer P., Tan D., Oberer M., Nelson A.T., Konduri S., RA Siegel D., Zechner R., Saghatelian A., Kahn B.B.; RT "ATGL is a biosynthetic enzyme for fatty acid esters of hydroxy fatty RT acids."; RL Nature 606:968-975(2022). CC -!- FUNCTION: Catalyzes the initial step in triglyceride hydrolysis in CC adipocyte and non-adipocyte lipid droplets (PubMed:15550674, CC PubMed:23066022, PubMed:15337759, PubMed:16150821, PubMed:16679289, CC PubMed:17074755, PubMed:16675698, PubMed:17114792). Exhibits a strong CC preference for the hydrolysis of long-chain fatty acid esters at the CC sn-2 position of the glycerol backbone and acts coordinately with CC LIPE/HLS and DGAT2 within the lipolytic cascade (PubMed:23066022). Also CC possesses acylglycerol transacylase and phospholipase A2 activities (By CC similarity). Transfers fatty acid from triglyceride to retinol, CC hydrolyzes retinylesters, and generates 1,3-diacylglycerol from CC triglycerides (By similarity). Regulates adiposome size and may be CC involved in the degradation of adiposomes (By similarity). May play an CC important role in energy homeostasis (PubMed:16675698). May play a role CC in the response of the organism to starvation, enhancing hydrolysis of CC triglycerides and providing free fatty acids to other tissues to be CC oxidized in situations of energy depletion (PubMed:15337759). Catalyzes CC the formation of an ester bond between hydroxy fatty acids and fatty CC acids derived from triglycerides or diglycerides to generate fatty acid CC esters of hydroxy fatty acids (FAHFAs) in adipocytes (PubMed:35676490). CC {ECO:0000250|UniProtKB:Q96AD5, ECO:0000269|PubMed:15337759, CC ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:16150821, CC ECO:0000269|PubMed:16675698, ECO:0000269|PubMed:16679289, CC ECO:0000269|PubMed:17074755, ECO:0000269|PubMed:17114792, CC ECO:0000269|PubMed:23066022, ECO:0000269|PubMed:35676490}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid + CC H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.3; CC Evidence={ECO:0000269|PubMed:15337759, ECO:0000269|PubMed:15550674, CC ECO:0000269|PubMed:16150821, ECO:0000269|PubMed:16675698, CC ECO:0000269|PubMed:16679289, ECO:0000269|PubMed:17074755, CC ECO:0000269|PubMed:17114792, ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12045; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a triacylglycerol + H2O = a 1,2-diacylglycerol + a fatty acid CC + H(+); Xref=Rhea:RHEA:35667, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17855, ChEBI:CHEBI:28868, ChEBI:CHEBI:49172; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35668; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a triacylglycerol + H2O = a 1,3-diacylglycerol + a fatty acid CC + H(+); Xref=Rhea:RHEA:38495, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17855, ChEBI:CHEBI:28868, ChEBI:CHEBI:47777; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38496; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a triacyl-sn-glycerol + H2O = a 2,3-diacyl-sn-glycerol + a CC fatty acid + H(+); Xref=Rhea:RHEA:38499, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:64615, CC ChEBI:CHEBI:75524; Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38500; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a triacyl-sn-glycerol + H2O = a 1,3-diacyl-sn-glycerol + a CC fatty acid + H(+); Xref=Rhea:RHEA:43732, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:64615, CC ChEBI:CHEBI:77272; Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43733; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)- CC octadecenoate + 1,3-di-(9Z-octadecenoyl)-glycerol + H(+); CC Xref=Rhea:RHEA:38387, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75735; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38388; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z)-hexadecenoylglycerol + H2O = (9Z)-hexadecenoate CC + 1,3-di-(9Z)-hexadecenoylglycerol + H(+); Xref=Rhea:RHEA:38395, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32372, CC ChEBI:CHEBI:75841, ChEBI:CHEBI:75849; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38396; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + H2O = (9Z,12Z)- CC octadecadienoate + 1,3-di-(9Z,12Z)-octadecadienoylglycerol + H(+); CC Xref=Rhea:RHEA:38403, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30245, ChEBI:CHEBI:75844, ChEBI:CHEBI:75850; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38404; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z,12Z,15Z)-octadecatrienoylglycerol + H2O = CC (9Z,12Z,15Z)-octadecatrienoate + 1,3-di-(9Z,12Z,15Z)- CC octadecatrienoylglycerol + H(+); Xref=Rhea:RHEA:38411, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32387, CC ChEBI:CHEBI:75845, ChEBI:CHEBI:75852; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38412; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,3-di-(9Z)-octadecenoyl-2-hexadecanoylglycerol + H2O = 1,3- CC di-(9Z-octadecenoyl)-glycerol + H(+) + hexadecanoate; CC Xref=Rhea:RHEA:38419, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:75735, ChEBI:CHEBI:75846; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38420; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + H2O = CC (9Z)-octadecenoate + 1-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + CC H(+); Xref=Rhea:RHEA:38423, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30823, ChEBI:CHEBI:75583, ChEBI:CHEBI:75867; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38424; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = CC (9Z)-octadecenoate + 1-hexadecanoyl-3-(9Z)-octadecenoyl-sn-glycerol + CC H(+); Xref=Rhea:RHEA:38647, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30823, ChEBI:CHEBI:75847, ChEBI:CHEBI:75868; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38648; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)- CC octadecenoate + 2,3-di-(9Z)-octadecenoyl-sn-glycerol + H(+); CC Xref=Rhea:RHEA:38391, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75824; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38392; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z)-hexadecenoylglycerol + H2O = (9Z)-hexadecenoate CC + 2,3-di-(9Z)-hexadecenoyl-sn-glycerol + H(+); Xref=Rhea:RHEA:38399, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32372, CC ChEBI:CHEBI:75841, ChEBI:CHEBI:75853; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38400; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + H2O = (9Z,12Z)- CC octadecadienoate + 2,3-di-(9Z,12Z)-octadecadienoyl-sn-glycerol + CC H(+); Xref=Rhea:RHEA:38407, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30245, ChEBI:CHEBI:75844, ChEBI:CHEBI:75854; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38408; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z,12Z,15Z)-octadecatrienoylglycerol + H2O = CC (9Z,12Z,15Z)-octadecatrienoate + 2,3-di-(9Z,12Z,15Z)- CC octadecatrienoyl-sn-glycerol + H(+); Xref=Rhea:RHEA:38415, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32387, CC ChEBI:CHEBI:75845, ChEBI:CHEBI:75855; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38416; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,3-di-(9Z)-octadecenoyl-2-hexadecanoylglycerol + H2O = (9Z)- CC octadecenoate + 2-hexadecanoyl-3-(9Z)-octadecenoyl-sn-glycerol + CC H(+); Xref=Rhea:RHEA:38431, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30823, ChEBI:CHEBI:75846, ChEBI:CHEBI:75870; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38432; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = CC 2,3-di-(9Z)-octadecenoyl-sn-glycerol + H(+) + hexadecanoate; CC Xref=Rhea:RHEA:38427, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:75824, ChEBI:CHEBI:75847; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38428; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + H2O = CC (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-3-hexadecanoyl-sn-glycerol + CC H(+); Xref=Rhea:RHEA:38643, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30823, ChEBI:CHEBI:75546, ChEBI:CHEBI:75583; CC Evidence={ECO:0000269|PubMed:23066022}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38644; CC Evidence={ECO:0000305|PubMed:23066022}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-glycerol + H(+) CC = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O; Xref=Rhea:RHEA:38379, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, CC ChEBI:CHEBI:52323, ChEBI:CHEBI:53753; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,3-diacylglycerol + a 1-acylglycerol = a triacylglycerol + CC glycerol; Xref=Rhea:RHEA:44440, ChEBI:CHEBI:17754, ChEBI:CHEBI:17855, CC ChEBI:CHEBI:35759, ChEBI:CHEBI:47777; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44441; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacylglycerol + a 1-acylglycerol = a triacylglycerol + CC glycerol; Xref=Rhea:RHEA:44436, ChEBI:CHEBI:17754, ChEBI:CHEBI:17855, CC ChEBI:CHEBI:35759, ChEBI:CHEBI:49172; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44437; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 a 1-acylglycerol = a 1,2-diacylglycerol + glycerol; CC Xref=Rhea:RHEA:44432, ChEBI:CHEBI:17754, ChEBI:CHEBI:35759, CC ChEBI:CHEBI:49172; Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44433; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a triacylglycerol + all-trans-retinol = a diacylglycerol + an CC all-trans-retinyl ester; Xref=Rhea:RHEA:44676, ChEBI:CHEBI:17336, CC ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:63410; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44677; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,3-di-(9Z-octadecenoyl)-glycerol + 1-(9Z-octadecenoyl)- CC glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerol; CC Xref=Rhea:RHEA:38331, ChEBI:CHEBI:17754, ChEBI:CHEBI:53753, CC ChEBI:CHEBI:75342, ChEBI:CHEBI:75735; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38332; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-di-(9Z-octadecenoyl)-glycerol + 1-(9Z-octadecenoyl)- CC glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerol; CC Xref=Rhea:RHEA:38327, ChEBI:CHEBI:17754, ChEBI:CHEBI:52323, CC ChEBI:CHEBI:53753, ChEBI:CHEBI:75342; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38328; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 1-(9Z-octadecenoyl)-glycerol = 1,2-di-(9Z-octadecenoyl)- CC glycerol + glycerol; Xref=Rhea:RHEA:38323, ChEBI:CHEBI:17754, CC ChEBI:CHEBI:52323, ChEBI:CHEBI:75342; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38324; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + all-trans-retinol = CC all-trans-retinyl 9Z-octadecenoate + di-(9Z)-octadecenoylglycerol; CC Xref=Rhea:RHEA:39987, ChEBI:CHEBI:17336, ChEBI:CHEBI:53753, CC ChEBI:CHEBI:70760, ChEBI:CHEBI:75945; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39988; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn- CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802; CC Evidence={ECO:0000250|UniProtKB:Q96AD5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + 9-hydroxy-octadecanoate CC = 2,3-di-(9Z)-octadecenoyl-sn-glycerol + 9-(9Z-octadecenoyloxy)- CC octadecanoate; Xref=Rhea:RHEA:75011, ChEBI:CHEBI:53753, CC ChEBI:CHEBI:75824, ChEBI:CHEBI:136282, ChEBI:CHEBI:136286; CC Evidence={ECO:0000269|PubMed:35676490}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + 9- CC hydroxy-octadecanoate = 2,3-di-(9Z)-octadecenoyl-sn-glycerol + 9- CC hexadecanoyloxy-octadecanoate; Xref=Rhea:RHEA:75015, CC ChEBI:CHEBI:75824, ChEBI:CHEBI:75847, ChEBI:CHEBI:83670, CC ChEBI:CHEBI:136286; Evidence={ECO:0000269|PubMed:35676490}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(10Z)-heptadecenoylglycerol + 9-hydroxy- CC octadecanoate = 2,3-di-(10Z-heptadecenoyl)-sn-glycerol + 9-(10Z- CC heptadecenoyloxy)-octadecanoate; Xref=Rhea:RHEA:75019, CC ChEBI:CHEBI:136286, ChEBI:CHEBI:194143, ChEBI:CHEBI:194145, CC ChEBI:CHEBI:228204; Evidence={ECO:0000269|PubMed:35676490}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + 9-hydroxy- CC octadecanoate = 2,3-di-(9Z,12Z)-octadecadienoyl-sn-glycerol + 9- CC (9Z,12Z-octadecadienoyloxy)-octadecanoate; Xref=Rhea:RHEA:75023, CC ChEBI:CHEBI:75844, ChEBI:CHEBI:75854, ChEBI:CHEBI:136286, CC ChEBI:CHEBI:194142; Evidence={ECO:0000269|PubMed:35676490}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(9Z)-hexadecenoylglycerol + 9-hydroxy-octadecanoate CC = 2,3-di-(9Z)-hexadecenoyl-sn-glycerol + 9-(9Z-hexadecenoyloxy)- CC octadecanoate; Xref=Rhea:RHEA:75027, ChEBI:CHEBI:75841, CC ChEBI:CHEBI:75853, ChEBI:CHEBI:136286, ChEBI:CHEBI:136309; CC Evidence={ECO:0000269|PubMed:35676490}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + 9-hydroxy-octadecanoate CC = 2-(9Z-octadecenoyl)-glycerol + 9-(9Z-octadecenoyloxy)- CC octadecanoate; Xref=Rhea:RHEA:75031, ChEBI:CHEBI:52333, CC ChEBI:CHEBI:73990, ChEBI:CHEBI:136282, ChEBI:CHEBI:136286; CC Evidence={ECO:0000269|PubMed:35676490}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + 9- CC hydroxy-octadecanoate = 1-hexadecanoyl-3-(9Z)-octadecenoyl-sn- CC glycerol + 9-(9Z-octadecenoyloxy)-octadecanoate; CC Xref=Rhea:RHEA:75035, ChEBI:CHEBI:75847, ChEBI:CHEBI:75868, CC ChEBI:CHEBI:136282, ChEBI:CHEBI:136286; CC Evidence={ECO:0000269|PubMed:35676490}; CC -!- ACTIVITY REGULATION: Stimulated by PKA-dependent PLIN phosphorylation. CC {ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:17074755, CC ECO:0000269|PubMed:17114792}. CC -!- PATHWAY: Glycerolipid metabolism; triacylglycerol degradation. CC -!- SUBUNIT: Interacts with ABHD5; this association stimulates PNPLA2 CC triglyceride hydrolase activity (PubMed:16679289, PubMed:17189257). CC Interacts with SERPINF1; this interaction stimulates the phospholipase CC A2 activity of PNPLA2 (By similarity). Despite a colocalization in CC lipid droplets, it probably does not interact with PLIN CC (PubMed:17189257). Interacts with PLIN5; prevents interaction with CC ABHD5 (PubMed:21148142, PubMed:21393244). Interacts with FAF2 (By CC similarity). {ECO:0000250|UniProtKB:Q96AD5, CC ECO:0000269|PubMed:16679289, ECO:0000269|PubMed:17189257, CC ECO:0000269|PubMed:21148142, ECO:0000269|PubMed:21393244}. CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:15550674, CC ECO:0000269|PubMed:16705060}. Cell membrane CC {ECO:0000250|UniProtKB:Q96AD5}; Multi-pass membrane protein CC {ECO:0000255}. Cytoplasm {ECO:0000269|PubMed:15337759}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8BJ56-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8BJ56-2; Sequence=VSP_026424; CC Name=3; CC IsoId=Q8BJ56-3; Sequence=VSP_026422, VSP_026423; CC -!- TISSUE SPECIFICITY: Expressed at high levels in white and brown adipose CC tissue, and to a lesser degree in testis and cardiac muscle. Barely CC detected in liver, spleen, thymus, kidney, skeletal muscle, and brain. CC Among the white adipose depots, gonadal fat showed the highest level of CC expression compared with inguinal and renal white adipose tissues. CC {ECO:0000269|PubMed:15337759, ECO:0000269|PubMed:15550674, CC ECO:0000269|PubMed:16150821, ECO:0000269|PubMed:16705060}. CC -!- DEVELOPMENTAL STAGE: Increased expression when preadipocytes are CC induced to differentiate to adipocytes. Not detected in proliferating CC or confluent preadipocytes. {ECO:0000269|PubMed:15337759, CC ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:16150821, CC ECO:0000269|PubMed:16705060}. CC -!- INDUCTION: Transiently induced during fasting. cAMP and glucagon may CC not be involved in the induction during fasting. Induced by CC dexamethasone. Down-regulated by insulin, isoprotenerol and TNF-alfa. CC Expression is not affected by glucose and by growth hormone. Expression CC is reduced in fasted leptin deficient mouse (ob/ob), an obese mouse CC model. Expression is not affected in fed ob/ob mouse. CC {ECO:0000269|PubMed:15337759, ECO:0000269|PubMed:16009485, CC ECO:0000269|PubMed:16150821, ECO:0000269|PubMed:16380488, CC ECO:0000269|PubMed:16705060}. CC -!- PTM: Phosphorylation at Ser-406 by PKA is increased during fasting and CC moderate intensity exercise, and moderately increases lipolytic CC activity. {ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:22733971}. CC -!- PTM: Ubiquitinated by PEX2 in response to reactive oxygen species CC (ROS), leading to its degradation. {ECO:0000250|UniProtKB:Q96AD5}. CC -!- DISRUPTION PHENOTYPE: Mice show increased adipose mass and CC triacylglycerol deposition in multiple tissues. They accumulate large CC amounts of lipid in the heart, causing cardiac dysfunction and CC premature death (PubMed:16675698). Conditional knockout in adipose CC cells results in a marked reduction in the levels and biosynthesis of CC fatty acid esters of hydroxy fatty acids (FAHFAs) and FAHFA-TGs CC (PubMed:35676490). {ECO:0000269|PubMed:16675698, CC ECO:0000269|PubMed:35676490}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB22643.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY731699; AAU33824.1; -; mRNA. DR EMBL; AY894805; AAW81963.1; -; mRNA. DR EMBL; AY510273; AAS48458.1; -; mRNA. DR EMBL; AK002826; BAB22387.1; -; mRNA. DR EMBL; AK003207; BAB22643.1; ALT_FRAME; mRNA. DR EMBL; AK031609; BAC27476.1; -; mRNA. DR EMBL; AK150184; BAE29364.1; -; mRNA. DR EMBL; BC019188; AAH19188.1; -; mRNA. DR EMBL; BC044781; AAH44781.1; -; mRNA. DR EMBL; BC064747; AAH64747.1; -; mRNA. DR EMBL; U89431; AAC36536.1; -; mRNA. DR CCDS; CCDS22015.1; -. [Q8BJ56-2] DR CCDS; CCDS52445.1; -. [Q8BJ56-1] DR RefSeq; NP_001157161.1; NM_001163689.1. [Q8BJ56-1] DR RefSeq; NP_080078.2; NM_025802.3. [Q8BJ56-2] DR AlphaFoldDB; Q8BJ56; -. DR SMR; Q8BJ56; -. DR BioGRID; 211763; 6. DR DIP; DIP-61641N; -. DR IntAct; Q8BJ56; 2. DR STRING; 10090.ENSMUSP00000127149; -. DR BindingDB; Q8BJ56; -. DR ChEMBL; CHEMBL3425391; -. DR SwissLipids; SLP:000000317; -. DR GlyCosmos; Q8BJ56; 1 site, No reported glycans. DR GlyGen; Q8BJ56; 1 site. DR iPTMnet; Q8BJ56; -. DR PhosphoSitePlus; Q8BJ56; -. DR SwissPalm; Q8BJ56; -. DR EPD; Q8BJ56; -. DR jPOST; Q8BJ56; -. DR MaxQB; Q8BJ56; -. DR PaxDb; 10090-ENSMUSP00000127149; -. DR PeptideAtlas; Q8BJ56; -. DR ProteomicsDB; 289932; -. [Q8BJ56-1] DR ProteomicsDB; 289933; -. [Q8BJ56-2] DR ProteomicsDB; 289934; -. [Q8BJ56-3] DR Pumba; Q8BJ56; -. DR Antibodypedia; 22689; 587 antibodies from 38 providers. DR Ensembl; ENSMUST00000064151.13; ENSMUSP00000065116.7; ENSMUSG00000025509.16. [Q8BJ56-2] DR Ensembl; ENSMUST00000164016.8; ENSMUSP00000127149.2; ENSMUSG00000025509.16. [Q8BJ56-1] DR GeneID; 66853; -. DR KEGG; mmu:66853; -. DR UCSC; uc009klg.2; mouse. [Q8BJ56-2] DR UCSC; uc009klh.2; mouse. [Q8BJ56-3] DR UCSC; uc009kli.2; mouse. [Q8BJ56-1] DR AGR; MGI:1914103; -. DR CTD; 57104; -. DR MGI; MGI:1914103; Pnpla2. DR VEuPathDB; HostDB:ENSMUSG00000025509; -. DR eggNOG; KOG3773; Eukaryota. DR GeneTree; ENSGT00940000160155; -. DR HOGENOM; CLU_018371_0_1_1; -. DR InParanoid; Q8BJ56; -. DR OMA; TKWEEYQ; -. DR OrthoDB; 5395310at2759; -. DR PhylomeDB; Q8BJ56; -. DR TreeFam; TF314272; -. DR BRENDA; 3.1.1.3; 3474. DR Reactome; R-MMU-1482883; Acyl chain remodeling of DAG and TAG. DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation. DR UniPathway; UPA00256; -. DR BioGRID-ORCS; 66853; 3 hits in 79 CRISPR screens. DR ChiTaRS; Pnpla2; mouse. DR PRO; PR:Q8BJ56; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; Q8BJ56; Protein. DR Bgee; ENSMUSG00000025509; Expressed in thoracic mammary gland and 245 other cell types or tissues. DR ExpressionAtlas; Q8BJ56; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:MGI. DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0016411; F:acylglycerol O-acyltransferase activity; ISO:MGI. DR GO; GO:0051265; F:diolein transacylation activity; ISS:UniProtKB. DR GO; GO:0051264; F:mono-olein transacylation activity; ISS:UniProtKB. DR GO; GO:0004623; F:phospholipase A2 activity; ISS:UniProtKB. DR GO; GO:0050253; F:retinyl-palmitate esterase activity; ISS:UniProtKB. DR GO; GO:0004806; F:triglyceride lipase activity; IDA:UniProtKB. DR GO; GO:0044242; P:cellular lipid catabolic process; IMP:MGI. DR GO; GO:0006651; P:diacylglycerol biosynthetic process; IDA:UniProtKB. DR GO; GO:1905691; P:lipid droplet disassembly; ISO:MGI. DR GO; GO:0034389; P:lipid droplet organization; IMP:MGI. DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central. DR GO; GO:0019915; P:lipid storage; IMP:UniProtKB. DR GO; GO:0010891; P:negative regulation of sequestering of triglyceride; IDA:UniProtKB. DR GO; GO:0010898; P:positive regulation of triglyceride catabolic process; IDA:UniProtKB. DR GO; GO:0019433; P:triglyceride catabolic process; IDA:UniProtKB. DR CDD; cd07220; Pat_PNPLA2; 1. DR Gene3D; 3.40.1090.10; Cytosolic phospholipase A2 catalytic domain; 1. DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase. DR InterPro; IPR033562; PLPL. DR InterPro; IPR033903; PNPLA2. DR InterPro; IPR002641; PNPLA_dom. DR PANTHER; PTHR12406; CALCIUM-INDEPENDENT PHOSPHOLIPASE A2 IPLA2 -RELATED; 1. DR PANTHER; PTHR12406:SF29; PATATIN-LIKE PHOSPHOLIPASE DOMAIN-CONTAINING PROTEIN 2; 1. DR Pfam; PF01734; Patatin; 1. DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1. DR PROSITE; PS51635; PNPLA; 1. DR Genevisible; Q8BJ56; MM. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cytoplasm; Glycoprotein; Hydrolase; KW Isopeptide bond; Lipid degradation; Lipid droplet; Lipid metabolism; KW Membrane; Phosphoprotein; Reference proteome; Signal-anchor; Transmembrane; KW Transmembrane helix; Ubl conjugation. FT CHAIN 1..486 FT /note="Patatin-like phospholipase domain-containing protein FT 2" FT /id="PRO_0000292528" FT TOPO_DOM 1..8 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q96AD5" FT TRANSMEM 9..29 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 30..42 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q96AD5" FT TRANSMEM 43..63 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 64..137 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q96AD5" FT TRANSMEM 138..158 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 159..331 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q96AD5" FT TRANSMEM 332..352 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 353..486 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q96AD5" FT DOMAIN 10..179 FT /note="PNPLA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161" FT REGION 465..486 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 14..19 FT /note="GXGXXG" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161" FT MOTIF 45..49 FT /note="GXSXG" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161" FT MOTIF 166..168 FT /note="DGA/G" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161" FT ACT_SITE 47 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161" FT ACT_SITE 166 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161" FT MOD_RES 374 FT /note="Phosphoserine; in vitro" FT /evidence="ECO:0000269|PubMed:22733971" FT MOD_RES 396 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:22733971" FT MOD_RES 406 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:22733971, FT ECO:0007744|PubMed:21183079" FT MOD_RES 430 FT /note="Phosphoserine; in vitro" FT /evidence="ECO:0000269|PubMed:22733971, FT ECO:0007744|PubMed:21183079" FT MOD_RES 468 FT /note="Phosphoserine; in vitro" FT /evidence="ECO:0000269|PubMed:22733971" FT CARBOHYD 39 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CROSSLNK 92 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q96AD5" FT VAR_SEQ 1..56 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_026422" FT VAR_SEQ 57..62 FT /note="VTGACL -> MSHACQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_026423" FT VAR_SEQ 253..308 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_026424" FT MUTAGEN 47 FT /note="S->A: Loss of triacylglycerol hydrolysis activity." FT /evidence="ECO:0000269|PubMed:16679289" FT MUTAGEN 396 FT /note="S->A: Slightly reduced TG hydrolase activity." FT /evidence="ECO:0000269|PubMed:22733971" FT MUTAGEN 406 FT /note="S->A: Reduced TG hydrolase activity." FT /evidence="ECO:0000269|PubMed:22733971" FT CONFLICT 3 FT /note="P -> T (in Ref. 4; BAB22387)" FT /evidence="ECO:0000305" FT CONFLICT 30 FT /note="R -> H (in Ref. 1; AAU33824)" FT /evidence="ECO:0000305" FT CONFLICT 193 FT /note="I -> V (in Ref. 4; BAE29364)" FT /evidence="ECO:0000305" FT CONFLICT 319..320 FT /note="DL -> VG (in Ref. 4; BAB22643)" FT /evidence="ECO:0000305" FT CONFLICT 362 FT /note="P -> T (in Ref. 4; BAE29364)" FT /evidence="ECO:0000305" FT CONFLICT 385 FT /note="R -> G (in Ref. 6; AAC36536)" FT /evidence="ECO:0000305" FT CONFLICT 389 FT /note="D -> G (in Ref. 5; AAH64747)" FT /evidence="ECO:0000305" FT CONFLICT 412 FT /note="L -> P (in Ref. 6; AAC36536)" FT /evidence="ECO:0000305" SQ SEQUENCE 486 AA; 53657 MW; 512FE1931B72FC9C CRC64; MFPRETKWNI SFAGCGFLGV YHIGVASCLR EHAPFLVANA THIYGASAGA LTATALVTGA CLGEAGANII EVSKEARKRF LGPLHPSFNL VKTIRGCLLK TLPADCHERA NGRLGISLTR VSDGENVIIS HFSSKDELIQ ANVCSTFIPV YCGLIPPTLQ GVRYVDGGIS DNLPLYELKN TITVSPFSGE SDICPQDSST NIHELRVTNT SIQFNLRNLY RLSKALFPPE PMVLREMCKQ GYRDGLRFLR RNGLLNQPNP LLALPPVVPQ EEDAEEAAVV EERAGEEDQL QPYRKDRILE HLPARLNEAL LEACVEPKDL MTTLSNMLPV RLATAMMVPY TLPLESAVSF TIRLLEWLPD VPEDIRWMKE QTGSICQYLV MRAKRKLGDH LPSRLSEQVE LRRAQSLPSV PLSCATYSEA LPNWVRNNLS LGDALAKWEE CQRQLLLGLF CTNVAFPPDA LRMRAPASPT AADPATPQDP PGLPPC //