ID PLPL2_HUMAN Reviewed; 504 AA. AC Q96AD5; O60643; Q5EFF5; Q6XYE5; Q96ET6; Q9NQ61; Q9NQ62; DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 164. DE RecName: Full=Patatin-like phospholipase domain-containing protein 2 {ECO:0000305}; DE EC=3.1.1.3 {ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:16150821, ECO:0000269|PubMed:16239926, ECO:0000269|PubMed:17603008}; DE AltName: Full=Adipose triglyceride lipase {ECO:0000303|PubMed:15550674}; DE AltName: Full=Calcium-independent phospholipase A2-zeta {ECO:0000303|PubMed:15364929}; DE Short=iPLA2-zeta {ECO:0000303|PubMed:15364929}; DE EC=3.1.1.4 {ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:17032652}; DE AltName: Full=Desnutrin; DE AltName: Full=Pigment epithelium-derived factor receptor {ECO:0000303|PubMed:17032652}; DE Short=PEDF-R {ECO:0000303|PubMed:17032652}; DE AltName: Full=TTS2.2 {ECO:0000303|PubMed:17603008}; DE AltName: Full=Transport-secretion protein 2; DE Short=TTS2; GN Name=PNPLA2 {ECO:0000312|HGNC:HGNC:30802}; GN Synonyms=ATGL {ECO:0000303|PubMed:15550674}; ORFNames=FP17548; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND RP CATALYTIC ACTIVITY. 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-481. RA Strahl T., Shingler W.H., Lammiman M., Gregory C.D., Leach L., Matthias P., RA Nielsen P.J., Shaw P.E.; RT "TTS-2, a novel protein implicated in vesicular transport of the cell RT surface receptor ICAM-3."; RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-481. RC TISSUE=Brain, and Eye; 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 94-504 (ISOFORM 1). RC TISSUE=Brain; RA Yu W., Gibbs R.A.; RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases. RN [7] RP FUNCTION, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY. RX PubMed=15364929; DOI=10.1074/jbc.m407841200; RA Jenkins C.M., Mancuso D.J., Yan W., Sims H.F., Gibson B., Gross R.W.; RT "Identification, cloning, expression, and purification of three novel human RT calcium-independent phospholipase A2 family members possessing RT triacylglycerol lipase and acylglycerol transacylase activities."; RL J. Biol. Chem. 279:48968-48975(2004). RN [8] RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY. RX PubMed=16249444; DOI=10.2337/diabetes.54.11.3190; RA Langin D., Dicker A., Tavernier G., Hoffstedt J., Mairal A., Ryden M., RA Arner E., Sicard A., Jenkins C.M., Viguerie N., van Harmelen V., RA Gross R.W., Holm C., Arner P.; RT "Adipocyte lipases and defect of lipolysis in human obesity."; RL Diabetes 54:3190-3197(2005). RN [9] RP TISSUE SPECIFICITY, MUTAGENESIS OF SER-47, CATALYTIC ACTIVITY, AND RP FUNCTION. 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 [10] RP DEVELOPMENTAL STAGE. 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 [11] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-47, AND CATALYTIC RP ACTIVITY. RX PubMed=16239926; DOI=10.1038/sj.embor.7400559; RA Smirnova E., Goldberg E.B., Makarova K.S., Lin L., Brown W.J., RA Jackson C.L.; RT "ATGL has a key role in lipid droplet/adiposome degradation in mammalian RT cells."; RL EMBO Rep. 7:106-113(2006). RN [12] RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH RP SERPINF1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, RP FUNCTION, CATALYTIC ACTIVITY, AND TOPOLOGY. RX PubMed=17032652; DOI=10.1074/jbc.m600353200; RA Notari L., Baladron V., Aroca-Aguilar J.D., Balko N., Heredia R., Meyer C., RA Notario P.M., Saravanamuthu S., Nueda M.-L., Sanchez-Sanchez F., RA Escribano J., Laborda J., Becerra S.P.; RT "Identification of a lipase-linked cell membrane receptor for pigment RT epithelium-derived factor."; RL J. Biol. Chem. 281:38022-38037(2006). RN [13] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=17603008; DOI=10.1016/j.bbrc.2007.06.089; RA Gao J.G., Simon M.; RT "A comparative study of human GS2, its paralogues, and its rat RT orthologue."; RL Biochem. Biophys. Res. Commun. 360:501-506(2007). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [16] RP PHOSPHORYLATION AT SER-404. 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-404 AND SER-428, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP INTERACTION WITH FAF2. RX PubMed=23297223; DOI=10.1073/pnas.1213738110; RA Olzmann J.A., Richter C.M., Kopito R.R.; RT "Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid RT droplet turnover."; RL Proc. Natl. Acad. Sci. U.S.A. 110:1345-1350(2013). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [20] RP PHOSPHORYLATION AT SER-404. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted phosphoproteome."; RL Cell 161:1619-1632(2015). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION AT LYS-92, AND MUTAGENESIS RP OF LYS-92. RX PubMed=34903883; DOI=10.1038/s42255-021-00489-2; RA Ding L., Sun W., Balaz M., He A., Klug M., Wieland S., Caiazzo R., RA Raverdy V., Pattou F., Lefebvre P., Lodhi I.J., Staels B., Heim M., RA Wolfrum C.; RT "Peroxisomal beta-oxidation acts as a sensor for intracellular fatty acids RT and regulates lipolysis."; RL Nat. Metab. 3:1648-1661(2021). RN [22] RP FUNCTION, AND CATALYTIC ACTIVITY. 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). RN [23] RP VARIANTS PHE-219; LYS-252 AND PRO-481, POLYMORPHISM, AND ASSOCIATION WITH RP DIABETES MELLITUS TYPE 2. RX PubMed=16644682; DOI=10.2337/db05-1498; RA Schoenborn V., Heid I.M., Vollmert C., Lingenhel A., Adams T.D., RA Hopkins P.N., Illig T., Zimmermann R., Zechner R., Hunt S.C., RA Kronenberg F.; RT "The ATGL gene is associated with free fatty acids, triglycerides, and type RT 2 diabetes."; RL Diabetes 55:1270-1275(2006). RN [24] RP VARIANT NLSDM LEU-195. RX PubMed=17187067; DOI=10.1038/ng1951; RA Fischer J., Lefevre C., Morava E., Mussini J.-M., Laforet P., RA Negre-Salvayre A., Lathrop M., Salvayre R.; RT "The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in RT neutral lipid storage disease with myopathy."; RL Nat. Genet. 39:28-30(2007). CC -!- FUNCTION: Catalyzes the initial step in triglyceride hydrolysis in CC adipocyte and non-adipocyte lipid droplets (PubMed:15550674, CC PubMed:15364929, PubMed:16150821, PubMed:17603008, PubMed:16239926, CC PubMed:34903883). Exhibits a strong preference for the hydrolysis of CC long-chain fatty acid esters at the sn-2 position of the glycerol CC backbone and acts coordinately with LIPE/HLS and DGAT2 within the CC lipolytic cascade (By similarity). Also possesses acylglycerol CC transacylase and phospholipase A2 activities (PubMed:15364929, CC PubMed:17032652, PubMed:17603008). Transfers fatty acid from CC triglyceride to retinol, hydrolyzes retinylesters, and generates 1,3- CC diacylglycerol from triglycerides (PubMed:17603008). Regulates CC adiposome size and may be involved in the degradation of adiposomes CC (PubMed:16239926). May play an important role in energy homeostasis (By CC similarity). May play a role in the response of the organism to CC starvation, enhancing hydrolysis of triglycerides and providing free CC fatty acids to other tissues to be oxidized in situations of energy CC depletion (By similarity). Catalyzes the formation of an ester bond CC between hydroxy fatty acids and fatty acids derived from triglycerides CC or diglycerides to generate fatty acid esters of hydroxy fatty acids CC (FAHFAs) in adipocytes (PubMed:35676490). CC {ECO:0000250|UniProtKB:Q8BJ56, ECO:0000269|PubMed:15364929, CC ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:16150821, CC ECO:0000269|PubMed:16239926, ECO:0000269|PubMed:17032652, CC ECO:0000269|PubMed:17603008, ECO:0000269|PubMed:34903883, CC 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:15364929, ECO:0000269|PubMed:15550674, CC ECO:0000269|PubMed:16150821, ECO:0000269|PubMed:16239926, CC ECO:0000269|PubMed:17603008}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12045; CC Evidence={ECO:0000305|PubMed:15550674, ECO:0000305|PubMed:16150821, CC ECO:0000305|PubMed:17603008}; 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:17603008}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35668; CC Evidence={ECO:0000305|PubMed:17603008}; 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:17603008, ECO:0000305|PubMed:15550674}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38496; CC Evidence={ECO:0000305|PubMed:15550674, ECO:0000305|PubMed:17603008}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43733; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38500; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000269|PubMed:15364929}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44441; CC Evidence={ECO:0000305|PubMed:15364929}; 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:0000269|PubMed:15364929}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44437; CC Evidence={ECO:0000305|PubMed:15364929}; 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:0000269|PubMed:15364929}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44433; CC Evidence={ECO:0000305|PubMed:15364929}; 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:0000269|PubMed:17603008}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44677; CC Evidence={ECO:0000305|PubMed:17603008}; 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:0000269|PubMed:17603008, ECO:0000305|PubMed:15550674}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381; CC Evidence={ECO:0000305|PubMed:15550674, ECO:0000305|PubMed:17603008}; 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:17603008}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38388; CC Evidence={ECO:0000305|PubMed:17603008}; 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:0000269|PubMed:15364929}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38332; CC Evidence={ECO:0000305|PubMed:15364929}; 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:0000269|PubMed:15364929}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38328; CC Evidence={ECO:0000305|PubMed:15364929}; 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:0000269|PubMed:15364929}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38324; CC Evidence={ECO:0000305|PubMed:15364929}; 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:0000269|PubMed:17603008}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39988; CC Evidence={ECO:0000305|PubMed:17603008}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38396; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38404; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38412; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38420; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38424; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38648; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38392; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38400; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38408; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38416; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38432; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38428; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q8BJ56}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38644; CC Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000269|PubMed:15364929, ECO:0000269|PubMed:17032652}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802; CC Evidence={ECO:0000305|PubMed:17032652}; 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: The triglyceride lipase activity is inhibited by CC BEL ((E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2- CC one), a suicide substrate inhibitor (PubMed:17032652). No differences CC in the acylglycerol transacylase was detected in the presence or CC absence of ATP (PubMed:15364929). {ECO:0000269|PubMed:15364929, CC ECO:0000269|PubMed:17032652}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 7.5 with (1,2-dilinoleoyl)-phosphatidylcholine as CC substrate. {ECO:0000269|PubMed:17032652}; CC -!- PATHWAY: Glycerolipid metabolism; triacylglycerol degradation. CC -!- SUBUNIT: Interacts with ABHD5; this association stimulates PNPLA2 CC triglyceride hydrolase activity (By similarity). Interacts with CC SERPINF1; this interaction stimulates the phospholipase A2 activity of CC PNPLA2 (PubMed:17032652). Despite a colocalization in lipid droplets, CC it probably does not interact with PLIN (By similarity). Interacts with CC PLIN5; prevents interaction with ABHD5 (By similarity). Interacts with CC FAF2 (PubMed:23297223). {ECO:0000250|UniProtKB:Q8BJ56, CC ECO:0000269|PubMed:17032652, ECO:0000269|PubMed:23297223}. CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:16239926, CC ECO:0000269|PubMed:34903883}. Cell membrane CC {ECO:0000269|PubMed:17032652}; Multi-pass membrane protein CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BJ56}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96AD5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96AD5-2; Sequence=VSP_026421; CC -!- TISSUE SPECIFICITY: Highest expression in adipose tissue. Also detected CC in heart, skeletal muscle, and portions of the gastrointestinal tract. CC Detected in normal retina and retinoblastoma cells. Detected in retinal CC pigment epithelium and, at lower intensity, in the inner segments of CC photoreceptors and in the ganglion cell layer of the neural retina (at CC protein level). {ECO:0000269|PubMed:15550674, CC ECO:0000269|PubMed:16150821, ECO:0000269|PubMed:16249444, CC ECO:0000269|PubMed:17032652}. CC -!- DEVELOPMENTAL STAGE: Induced during differentiation of primary CC preadipocytes to adipocytes. Expression increased from fetal to adult CC in retinal pigment epithelium. {ECO:0000269|PubMed:16249444, CC ECO:0000269|PubMed:16705060, ECO:0000269|PubMed:17032652}. CC -!- PTM: Phosphorylation at Ser-404 by PKA is increased during fasting and CC moderate intensity exercise, and moderately increases lipolytic CC activity (By similarity). Phosphorylation at Ser-404 is increased upon CC beta-adrenergic stimulation (PubMed:22733971). CC {ECO:0000250|UniProtKB:Q8BJ56, ECO:0000269|PubMed:22733971}. CC -!- PTM: Ubiquitinated by PEX2 in response to reactive oxygen species CC (ROS), leading to its degradation. {ECO:0000269|PubMed:34903883}. CC -!- POLYMORPHISM: Genetic variations in PNPLA2 may influence plasma free CC fatty acids and triglycerides levels, and fasting glucose CC concentrations. {ECO:0000269|PubMed:16644682}. CC -!- DISEASE: Note=Genetic variations in PNPLA2 may be associated with risk CC of diabetes mellitus type 2. {ECO:0000269|PubMed:16644682}. CC -!- DISEASE: Neutral lipid storage disease with myopathy (NLSDM) CC [MIM:610717]: Neutral lipid storage disorder (NLSD) with myopathy but CC without ichthyosis. NLSDs are characterized by the presence of CC triglyceride-containing cytoplasmic droplets in leukocytes and in other CC tissues, including bone marrow, skin, and muscle. Individuals with CC NLSDM did not show obesity, in spite of a defect in triglyceride CC degradation in fibroblasts and in marked triglyceride storage in liver, CC muscles, and other visceral cells. {ECO:0000269|PubMed:17187067}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAP34448.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAC01131.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAC01132.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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; AY894804; AAW81962.1; -; mRNA. DR EMBL; AJ278475; CAC01131.1; ALT_INIT; mRNA. DR EMBL; AJ278476; CAC01132.1; ALT_INIT; mRNA. DR EMBL; AY203925; AAP34448.1; ALT_FRAME; mRNA. DR EMBL; AP006621; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC011958; AAH11958.1; -; mRNA. DR EMBL; BC017280; AAH17280.1; -; mRNA. DR EMBL; AF055000; AAC09354.1; -; mRNA. DR CCDS; CCDS7718.1; -. [Q96AD5-1] DR RefSeq; NP_065109.1; NM_020376.3. [Q96AD5-1] DR RefSeq; XP_016873517.1; XM_017018028.1. DR AlphaFoldDB; Q96AD5; -. DR SMR; Q96AD5; -. DR BioGRID; 121370; 48. DR IntAct; Q96AD5; 12. DR MINT; Q96AD5; -. DR STRING; 9606.ENSP00000337701; -. DR BindingDB; Q96AD5; -. DR ChEMBL; CHEMBL3822353; -. DR SwissLipids; SLP:000000311; -. DR GlyCosmos; Q96AD5; 2 sites, 1 glycan. DR GlyGen; Q96AD5; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q96AD5; -. DR PhosphoSitePlus; Q96AD5; -. DR SwissPalm; Q96AD5; -. DR BioMuta; PNPLA2; -. DR DMDM; 74731110; -. DR EPD; Q96AD5; -. DR jPOST; Q96AD5; -. DR MassIVE; Q96AD5; -. DR MaxQB; Q96AD5; -. DR PaxDb; 9606-ENSP00000337701; -. DR PeptideAtlas; Q96AD5; -. DR ProteomicsDB; 75955; -. [Q96AD5-1] DR ProteomicsDB; 75956; -. [Q96AD5-2] DR Pumba; Q96AD5; -. DR Antibodypedia; 22689; 587 antibodies from 38 providers. DR DNASU; 57104; -. DR Ensembl; ENST00000336615.9; ENSP00000337701.4; ENSG00000177666.17. [Q96AD5-1] DR GeneID; 57104; -. DR KEGG; hsa:57104; -. DR MANE-Select; ENST00000336615.9; ENSP00000337701.4; NM_020376.4; NP_065109.1. DR UCSC; uc001lrt.4; human. [Q96AD5-1] DR AGR; HGNC:30802; -. DR CTD; 57104; -. DR DisGeNET; 57104; -. DR GeneCards; PNPLA2; -. DR HGNC; HGNC:30802; PNPLA2. DR HPA; ENSG00000177666; Tissue enhanced (adipose tissue, breast). DR MalaCards; PNPLA2; -. DR MIM; 609059; gene. DR MIM; 610717; phenotype. DR neXtProt; NX_Q96AD5; -. DR OpenTargets; ENSG00000177666; -. DR Orphanet; 98908; Neutral lipid storage myopathy. DR Orphanet; 565612; Primary triglyceride deposit cardiomyovasculopathy. DR PharmGKB; PA134903083; -. DR VEuPathDB; HostDB:ENSG00000177666; -. DR eggNOG; KOG3773; Eukaryota. DR GeneTree; ENSGT00940000160155; -. DR HOGENOM; CLU_018371_0_1_1; -. DR InParanoid; Q96AD5; -. DR OMA; TKWEEYQ; -. DR OrthoDB; 5395310at2759; -. DR PhylomeDB; Q96AD5; -. DR TreeFam; TF314272; -. DR PathwayCommons; Q96AD5; -. DR Reactome; R-HSA-1482883; Acyl chain remodeling of DAG and TAG. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR SignaLink; Q96AD5; -. DR UniPathway; UPA00256; -. DR BioGRID-ORCS; 57104; 12 hits in 1157 CRISPR screens. DR ChiTaRS; PNPLA2; human. DR GeneWiki; PNPLA2; -. DR GenomeRNAi; 57104; -. DR Pharos; Q96AD5; Tchem. DR PRO; PR:Q96AD5; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q96AD5; Protein. DR Bgee; ENSG00000177666; Expressed in omental fat pad and 187 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0005811; C:lipid droplet; IDA:HPA. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0016411; F:acylglycerol O-acyltransferase activity; IDA:UniProtKB. DR GO; GO:0051265; F:diolein transacylation activity; IDA:UniProtKB. DR GO; GO:0004465; F:lipoprotein lipase activity; TAS:Reactome. DR GO; GO:0051264; F:mono-olein transacylation activity; IDA:UniProtKB. DR GO; GO:0004623; F:phospholipase A2 activity; IDA:UniProtKB. DR GO; GO:0050253; F:retinyl-palmitate esterase activity; EXP:UniProtKB. DR GO; GO:0004806; F:triglyceride lipase activity; IDA:UniProtKB. DR GO; GO:0036155; P:acylglycerol acyl-chain remodeling; TAS:Reactome. DR GO; GO:0006651; P:diacylglycerol biosynthetic process; ISS:UniProtKB. DR GO; GO:1905691; P:lipid droplet disassembly; IMP:UniProtKB. DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central. DR GO; GO:0019915; P:lipid storage; IEA:Ensembl. 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; ISS:UniProtKB. DR CDD; cd07220; Pat_PNPLA2; 1. DR Gene3D; 3.40.1090.10; Cytosolic phospholipase A2 catalytic domain; 2. 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; Q96AD5; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cytoplasm; Disease variant; KW Glycoprotein; Hydrolase; Isopeptide bond; Lipid degradation; Lipid droplet; KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome; KW Signal-anchor; Transmembrane; Transmembrane helix; Ubl conjugation. FT CHAIN 1..504 FT /note="Patatin-like phospholipase domain-containing protein FT 2" FT /id="PRO_0000292527" FT TOPO_DOM 1..8 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:17032652" FT TRANSMEM 9..29 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 30..42 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:17032652" FT TRANSMEM 43..63 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 64..137 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:17032652" FT TRANSMEM 138..158 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 159..329 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:17032652" FT TRANSMEM 330..350 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 351..504 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:17032652" FT DOMAIN 10..179 FT /note="PNPLA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161" FT REGION 463..492 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 372 FT /note="Phosphoserine; in vitro" FT /evidence="ECO:0000250|UniProtKB:Q8BJ56" FT MOD_RES 404 FT /note="Phosphoserine; by PKA and FAM20C" FT /evidence="ECO:0000269|PubMed:22733971, FT ECO:0000269|PubMed:26091039, ECO:0007744|PubMed:23186163" FT MOD_RES 428 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" 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:0000269|PubMed:34903883" FT VAR_SEQ 1..324 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15498874" FT /id="VSP_026421" FT VARIANT 195 FT /note="P -> L (in NLSDM; dbSNP:rs121918259)" FT /evidence="ECO:0000269|PubMed:17187067" FT /id="VAR_032995" FT VARIANT 219 FT /note="L -> F (in dbSNP:rs140612115)" FT /evidence="ECO:0000269|PubMed:16644682" FT /id="VAR_032996" FT VARIANT 252 FT /note="N -> K (in dbSNP:rs140201358)" FT /evidence="ECO:0000269|PubMed:16644682" FT /id="VAR_032997" FT VARIANT 481 FT /note="L -> P (in dbSNP:rs1138693)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:16644682, ECO:0000269|Ref.2" FT /id="VAR_032998" FT MUTAGEN 47 FT /note="S->A: Reduces rate of lipid hydrolysis; does not FT affect the localization around the rim of the adiposomes." FT /evidence="ECO:0000269|PubMed:16150821, FT ECO:0000269|PubMed:16239926" FT MUTAGEN 92 FT /note="K->R: Abolished ubiquitination by PEX2." FT /evidence="ECO:0000269|PubMed:34903883" FT CONFLICT 163 FT /note="R -> G (in Ref. 6; AAC09354)" FT /evidence="ECO:0000305" FT CONFLICT 296 FT /note="I -> V (in Ref. 1; AAW81962)" FT /evidence="ECO:0000305" FT CONFLICT 333 FT /note="A -> G (in Ref. 3; AAP34448)" FT /evidence="ECO:0000305" FT CONFLICT 351 FT /note="R -> C (in Ref. 1; AAW81962)" FT /evidence="ECO:0000305" FT CONFLICT 402 FT /note="V -> L (in Ref. 2; CAC01131/CAC01132)" FT /evidence="ECO:0000305" FT CONFLICT 419 FT /note="L -> P (in Ref. 1; AAW81962)" FT /evidence="ECO:0000305" SQ SEQUENCE 504 AA; 55316 MW; D9C16F942AB0B3C7 CRC64; MFPREKTWNI SFAGCGFLGV YYVGVASCLR EHAPFLVANA THIYGASAGA LTATALVTGV CLGEAGAKFI EVSKEARKRF LGPLHPSFNL VKIIRSFLLK VLPADSHEHA SGRLGISLTR VSDGENVIIS HFNSKDELIQ ANVCSGFIPV YCGLIPPSLQ GVRYVDGGIS DNLPLYELKN TITVSPFSGE SDICPQDSST NIHELRVTNT SIQFNLRNLY RLSKALFPPE PLVLREMCKQ GYRDGLRFLQ RNGLLNRPNP LLALPPARPH GPEDKDQAVE SAQAEDYSQL PGEDHILEHL PARLNEALLE ACVEPTDLLT TLSNMLPVRL ATAMMVPYTL PLESALSFTI RLLEWLPDVP EDIRWMKEQT GSICQYLVMR AKRKLGRHLP SRLPEQVELR RVQSLPSVPL SCAAYREALP GWMRNNLSLG DALAKWEECQ RQLLLGLFCT NVAFPPEALR MRAPADPAPA PADPASPQHQ LAGPAPLLST PAPEARPVIG ALGL //