PLPL9_RAT
ID PLPL9_RAT Reviewed; 807 AA.
AC P97570; G3V7M8; Q66HD1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=85/88 kDa calcium-independent phospholipase A2;
DE Short=CaI-PLA2;
DE EC=3.1.1.4 {ECO:0000269|PubMed:18937505, ECO:0000269|PubMed:9111008};
DE AltName: Full=2-lysophosphatidylcholine acylhydrolase;
DE EC=3.1.1.5 {ECO:0000250|UniProtKB:O60733};
DE AltName: Full=Group VI phospholipase A2;
DE Short=GVI PLA2;
DE AltName: Full=Intracellular membrane-associated calcium-independent phospholipase A2 beta;
DE Short=iPLA2-beta;
DE AltName: Full=Palmitoyl-CoA hydrolase;
DE EC=3.1.2.2 {ECO:0000269|PubMed:18937505};
DE AltName: Full=Patatin-like phospholipase domain-containing protein 9;
DE Short=PNPLA9;
GN Name=Pla2g6; Synonyms=Pnpla9;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Pancreatic islet;
RX PubMed=9111008; DOI=10.1074/jbc.272.17.11250;
RA Ma Z., Ramanadham S., Kempe K., Chi X.S., Ladenson J., Turk J.;
RT "Pancreatic islets express a Ca2+-independent phospholipase A2 enzyme that
RT contains a repeated structural homologous to the integral membrane protein
RT binding domain of ankyrin.";
RL J. Biol. Chem. 272:11118-11127(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Li P.W., Adams M.D., Amanatides P.G., Baden-Tillson H.,
RA Barnstead M., Chin S.H., Dew I., Evans C.A., Ferriera S., Flanigan M.,
RA Fosler C., Glodek A., Gu Z., Holt R.A., Jennings D., Kraft C.L., Lu F.,
RA Nguyen T., Nusskern D.R., Pfannkoch C.M., Sitter C., Sutton G.G.,
RA Venter J.C., Wang Z., Woodage T., Zheng X.H., Zhong F.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Testis;
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 [5]
RP ACTIVITY REGULATION, AND CALMODULIN-BINDING REGIONS.
RX PubMed=11118454; DOI=10.1074/jbc.m010439200;
RA Jenkins C.M., Wolf M.J., Mancuso D.J., Gross R.W.;
RT "Identification of the calmodulin-binding domain of recombinant calcium-
RT independent phospholipase A2beta. implications for structure and
RT function.";
RL J. Biol. Chem. 276:7129-7135(2001).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND ACTIVITY REGULATION.
RX PubMed=18937505; DOI=10.1021/bi800923s;
RA Carper M.J., Zhang S., Turk J., Ramanadham S.;
RT "Skeletal muscle group VIA phospholipase A2 (iPLA2beta): expression and
RT role in fatty acid oxidation.";
RL Biochemistry 47:12241-12249(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24648512; DOI=10.1074/jbc.m114.561910;
RA Song H., Wohltmann M., Tan M., Ladenson J.H., Turk J.;
RT "Group VIA phospholipase A2 mitigates palmitate-induced beta-cell
RT mitochondrial injury and apoptosis.";
RL J. Biol. Chem. 289:14194-14210(2014).
CC -!- FUNCTION: Calcium-independent phospholipase involved in phospholipid
CC remodeling with implications in cellular membrane homeostasis,
CC mitochondrial integrity and signal transduction. Hydrolyzes the ester
CC bond of the fatty acyl group attached at sn-1 or sn-2 position of
CC phospholipids (phospholipase A1 and A2 activity respectively),
CC producing lysophospholipids that are used in deacylation-reacylation
CC cycles (PubMed:18937505, PubMed:9111008). Hydrolyzes both saturated and
CC unsaturated long fatty acyl chains in various glycerophospholipid
CC classes such as phosphatidylcholines, phosphatidylethanolamines and
CC phosphatidates, with a preference for hydrolysis at sn-2 position. Can
CC further hydrolyze lysophospholipids carrying saturated fatty acyl
CC chains (lysophospholipase activity) (PubMed:18937505). Upon oxidative
CC stress, contributes to remodeling of mitochondrial phospholipids in
CC pancreatic beta cells, in a repair mechanism to reduce oxidized lipid
CC content (PubMed:24648512). Preferentially hydrolyzes oxidized
CC polyunsaturated fatty acyl chains from cardiolipins, yielding
CC monolysocardiolipins that can be reacylated with unoxidized fatty acyls
CC to regenerate native cardiolipin species. Hydrolyzes oxidized
CC glycerophosphoethanolamines present in pancreatic islets, releasing
CC oxidized polyunsaturated fatty acids such as hydroxyeicosatetraenoates
CC (HETEs) (PubMed:24648512). Has thioesterase activity toward fatty-acyl
CC CoA releasing CoA-SH known to facilitate fatty acid transport and beta-
CC oxidation in mitochondria particularly in skeletal muscle
CC (PubMed:18937505). Plays a role in regulation of membrane dynamics and
CC homeostasis. Selectively hydrolyzes sn-2 arachidonoyl group in
CC plasmalogen phospholipids, structural components of lipid rafts and
CC myelin (By similarity). Regulates F-actin polymerization at the
CC pseudopods, which is required for both speed and directionality of
CC MCP1/CCL2-induced monocyte chemotaxis (By similarity). Targets membrane
CC phospholipids to produce potent lipid signaling messengers. Generates
CC lysophosphatidate (LPA, 1-acyl-glycerol-3-phosphate), which acts via G-
CC protein receptors in various cell types. Has phospholipase A2 activity
CC toward platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-
CC 3-phosphocholine), likely playing a role in inactivation of this potent
CC pro-inflammatory signaling lipid (By similarity). In response to
CC glucose, amplifies calcium influx in pancreatic beta cells to promote
CC INS secretion (By similarity). {ECO:0000250|UniProtKB:A0A3L7I2I8,
CC ECO:0000250|UniProtKB:O60733, ECO:0000250|UniProtKB:P97819,
CC ECO:0000269|PubMed:18937505, ECO:0000269|PubMed:24648512,
CC ECO:0000269|PubMed:9111008}.
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:18937505, ECO:0000269|PubMed:9111008};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802;
CC Evidence={ECO:0000305|PubMed:18937505, ECO:0000305|PubMed:9111008};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-
CC hexadecanoyl-sn-glycero-3-phosphocholine + H(+) + hexadecanoate;
CC Xref=Rhea:RHEA:41223, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:72998, ChEBI:CHEBI:72999;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41224;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine
CC + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-
CC phosphocholine + H(+); Xref=Rhea:RHEA:38779, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:72998,
CC ChEBI:CHEBI:73001; Evidence={ECO:0000250|UniProtKB:O60733};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38780;
CC Evidence={ECO:0000250|UniProtKB:O60733};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-
CC glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:40811,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30245,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:73002;
CC Evidence={ECO:0000269|PubMed:18937505, ECO:0000269|PubMed:9111008};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812;
CC Evidence={ECO:0000305|PubMed:18937505, ECO:0000305|PubMed:9111008};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-
CC hexadecanoyl-sn-glycero-3-phosphocholine + H(+);
CC Xref=Rhea:RHEA:40427, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:72998, ChEBI:CHEBI:73003;
CC Evidence={ECO:0000250|UniProtKB:O60733};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40428;
CC Evidence={ECO:0000250|UniProtKB:O60733};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-
CC octadecanoyl-sn-glycero-3-phosphocholine + H(+);
CC Xref=Rhea:RHEA:40519, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:73858, ChEBI:CHEBI:74965;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40520;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphoethanolamine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-
CC hexadecanoyl-sn-glycero-3-phosphoethanolamine + H(+);
CC Xref=Rhea:RHEA:40431, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:73004, ChEBI:CHEBI:73009;
CC Evidence={ECO:0000250|UniProtKB:P97819};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40432;
CC Evidence={ECO:0000250|UniProtKB:P97819};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1-
CC hexadecanoyl-sn-glycero-3-phosphate + H(+) + hexadecanoate;
CC Xref=Rhea:RHEA:63304, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57518, ChEBI:CHEBI:72859;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63305;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphocholine + H2O = a fatty acid +
CC H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:15177,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870,
CC ChEBI:CHEBI:28868, ChEBI:CHEBI:58168; EC=3.1.1.5;
CC Evidence={ECO:0000250|UniProtKB:O60733};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15178;
CC Evidence={ECO:0000250|UniProtKB:O60733};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) +
CC hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40435,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16870, ChEBI:CHEBI:72998;
CC Evidence={ECO:0000250|UniProtKB:O60733};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC Evidence={ECO:0000250|UniProtKB:O60733};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine
CC + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + sn-glycerol 3-
CC phosphocholine; Xref=Rhea:RHEA:40831, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:74344; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40832;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine
CC + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + sn-glycerol 3-
CC phosphocholine; Xref=Rhea:RHEA:40827, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:76079; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40828;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-
CC phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-O-
CC hexadecyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:41067,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:55430, ChEBI:CHEBI:64496;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41068;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-
CC O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H(+);
CC Xref=Rhea:RHEA:40479, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:44811, ChEBI:CHEBI:64496;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40480;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexadecanoyl-CoA = CoA + H(+) + hexadecanoate;
CC Xref=Rhea:RHEA:16645, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379; EC=3.1.2.2;
CC Evidence={ECO:0000269|PubMed:18937505};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000305|PubMed:18937505};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1',3'-bis[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-
CC glycerol + H2O = (9Z)-octadecenoate + 1'-[1,2-di-(9Z-octadecenoyl)-
CC sn-glycero-3-phospho]-3'-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-
CC glycerol + H(+); Xref=Rhea:RHEA:40463, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:77253,
CC ChEBI:CHEBI:77259; Evidence={ECO:0000250|UniProtKB:O60733};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40464;
CC Evidence={ECO:0000250|UniProtKB:O60733};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1'-[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-3'-[1-(9Z-
CC octadecenoyl)-sn-glycero-3-phospho]-glycerol + H2O = (9Z)-
CC octadecenoate + 1',3'-bis-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-
CC glycerol + H(+); Xref=Rhea:RHEA:40467, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:77256,
CC ChEBI:CHEBI:77259; Evidence={ECO:0000250|UniProtKB:O60733};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40468;
CC Evidence={ECO:0000250|UniProtKB:O60733};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1',3'-bis-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phospho]-glycerol + H2O = (9Z,12Z)-octadecadienoate + 1'-[1,2-di-
CC (9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phospho]-glycerol + H(+);
CC Xref=Rhea:RHEA:52812, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:83580, ChEBI:CHEBI:83581;
CC Evidence={ECO:0000269|PubMed:24648512};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:52814;
CC Evidence={ECO:0000305|PubMed:24648512};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(15-hydroxy-(5Z,8Z,11Z,13E)-
CC eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-
CC octadecanoyl-sn-glycero-3-phosphoethanolamine + 15-hydroxy-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate + H(+); Xref=Rhea:RHEA:63256,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:75036,
CC ChEBI:CHEBI:78832, ChEBI:CHEBI:146277;
CC Evidence={ECO:0000269|PubMed:24648512};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63257;
CC Evidence={ECO:0000305|PubMed:24648512};
CC -!- ACTIVITY REGULATION: Activated by ATP (PubMed:18937505,
CC PubMed:9111008). Inhibited by calcium-activated calmodulin
CC (PubMed:11118454, PubMed:18937505). Inhibited by bromoenol lactone
CC (BEL) (PubMed:18937505). {ECO:0000269|PubMed:11118454,
CC ECO:0000269|PubMed:18937505, ECO:0000269|PubMed:9111008}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:9111008};
CC -!- SUBUNIT: Homodimer formed by catalytic domains tightly interacting
CC through a large hydrophobic interface. The contact area involves 3
CC alpha helices, several loops and a part of the beta sheet from each
CC monomer. Both active sites of the dimer are in close proximity adopting
CC an open conformation that provide sufficient space for phospholipid
CC access and favoring cooperativity in deacylation-reacylation reactions.
CC Each monomer has 9 ankyrin repeats stacked side-by-side in an elongated
CC structure oriented outwards from the catalytic core.
CC {ECO:0000250|UniProtKB:A0A3L7I2I8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O60733}. Cell
CC membrane {ECO:0000250|UniProtKB:O60733}. Mitochondrion
CC {ECO:0000250|UniProtKB:P97819}. Cell projection, pseudopodium
CC {ECO:0000250|UniProtKB:O60733}. Note=Recruited to the membrane-enriched
CC pseudopods upon MCP1/CCL2 stimulation in monocytes.
CC {ECO:0000250|UniProtKB:O60733}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P97570-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P97570-2; Sequence=VSP_044365;
CC -!- TISSUE SPECIFICITY: Expressed in pancreatic beta-cells
CC (PubMed:9111008). Expressed in skeletal muscle (at protein level)
CC (PubMed:18937505). {ECO:0000269|PubMed:18937505,
CC ECO:0000269|PubMed:9111008}.
CC -!- DOMAIN: Has two putative calmodulin binding domains, the 1-9-14 and IQ
CC motifs (PubMed:11118454). One calmodulin molecule interacts with PLA2G6
CC dimer, likely through 1-9-14 motif on each monomer (By similarity).
CC Binds calmodulin in a calcium-dependent way (PubMed:11118454).
CC {ECO:0000250|UniProtKB:A0A3L7I2I8, ECO:0000269|PubMed:11118454}.
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; U51898; AAC53136.1; -; mRNA.
DR EMBL; AABR06052011; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473950; EDM15808.1; -; Genomic_DNA.
DR EMBL; CH473950; EDM15809.1; -; Genomic_DNA.
DR EMBL; BC081916; AAH81916.1; -; mRNA.
DR RefSeq; NP_001005560.1; NM_001005560.1. [P97570-1]
DR RefSeq; NP_001257725.1; NM_001270796.1. [P97570-2]
DR AlphaFoldDB; P97570; -.
DR SMR; P97570; -.
DR IntAct; P97570; 1.
DR STRING; 10116.ENSRNOP00000017104; -.
DR ChEMBL; CHEMBL1075318; -.
DR iPTMnet; P97570; -.
DR PhosphoSitePlus; P97570; -.
DR PaxDb; P97570; -.
DR PRIDE; P97570; -.
DR GeneID; 360426; -.
DR KEGG; rno:360426; -.
DR UCSC; RGD:628867; rat. [P97570-1]
DR CTD; 8398; -.
DR RGD; 628867; Pla2g6.
DR VEuPathDB; HostDB:ENSRNOG00000012295; -.
DR eggNOG; KOG0513; Eukaryota.
DR HOGENOM; CLU_010817_0_0_1; -.
DR InParanoid; P97570; -.
DR OMA; MLAIEMH; -.
DR OrthoDB; 841851at2759; -.
DR PhylomeDB; P97570; -.
DR TreeFam; TF319230; -.
DR Reactome; R-RNO-1482788; Acyl chain remodelling of PC.
DR Reactome; R-RNO-1482839; Acyl chain remodelling of PE.
DR Reactome; R-RNO-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-RNO-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR PRO; PR:P97570; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Proteomes; UP000234681; Chromosome 7.
DR Bgee; ENSRNOG00000012295; Expressed in testis and 20 other tissues.
DR Genevisible; P97570; RN.
DR GO; GO:0034451; C:centriolar satellite; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031143; C:pseudopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0003847; F:1-alkyl-2-acetylglycerophosphocholine esterase activity; ISS:UniProtKB.
DR GO; GO:0043008; F:ATP-dependent protein binding; IDA:RGD.
DR GO; GO:0047499; F:calcium-independent phospholipase A2 activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004622; F:lysophospholipase activity; ISS:UniProtKB.
DR GO; GO:0102991; F:myristoyl-CoA hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0016290; F:palmitoyl-CoA hydrolase activity; IDA:UniProtKB.
DR GO; GO:0102545; F:phosphatidyl phospholipase B activity; IEA:UniProtKB-EC.
DR GO; GO:0004623; F:phospholipase A2 activity; TAS:Reactome.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0017171; F:serine hydrolase activity; ISO:RGD.
DR GO; GO:0019731; P:antibacterial humoral response; ISO:RGD.
DR GO; GO:0035965; P:cardiolipin acyl-chain remodeling; IDA:UniProtKB.
DR GO; GO:0032049; P:cardiolipin biosynthetic process; ISO:RGD.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD.
DR GO; GO:0007613; P:memory; IMP:RGD.
DR GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; IMP:RGD.
DR GO; GO:0046473; P:phosphatidic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0034638; P:phosphatidylcholine catabolic process; ISS:UniProtKB.
DR GO; GO:0046338; P:phosphatidylethanolamine catabolic process; ISS:UniProtKB.
DR GO; GO:0046469; P:platelet activating factor metabolic process; ISS:UniProtKB.
DR GO; GO:0090238; P:positive regulation of arachidonic acid secretion; IDA:RGD.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; IDA:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD.
DR GO; GO:0045921; P:positive regulation of exocytosis; IMP:RGD.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IDA:RGD.
DR GO; GO:0090037; P:positive regulation of protein kinase C signaling; IMP:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:RGD.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IDA:RGD.
DR GO; GO:1901339; P:regulation of store-operated calcium channel activity; IMP:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:RGD.
DR GO; GO:0014832; P:urinary bladder smooth muscle contraction; IMP:RGD.
DR GO; GO:0042311; P:vasodilation; IMP:RGD.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR002641; PNPLA_dom.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF13857; Ank_5; 1.
DR Pfam; PF01734; Patatin; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 6.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
DR PROSITE; PS51635; PNPLA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Calmodulin-binding; Cell membrane;
KW Cell projection; Chemotaxis; Cytoplasm; Hydrolase; Lipid metabolism;
KW Membrane; Mitochondrion; Phospholipid metabolism; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..807
FT /note="85/88 kDa calcium-independent phospholipase A2"
FT /id="PRO_0000067039"
FT TRANSMEM 481..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 512..532
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 120..147
FT /note="ANK 1"
FT /evidence="ECO:0000250|UniProtKB:A0A3L7I2I8"
FT REPEAT 151..181
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 185..215
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 219..248
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 251..281
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 286..312
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 316..345
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REPEAT 349..378
FT /note="ANK 7"
FT /evidence="ECO:0000255"
FT REPEAT 382..403
FT /note="ANK 9"
FT /evidence="ECO:0000250|UniProtKB:A0A3L7I2I8"
FT DOMAIN 482..666
FT /note="PNPLA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT REGION 678..687
FT /note="Calmodulin-binding (1-9-14 motif)"
FT /evidence="ECO:0000269|PubMed:11118454"
FT REGION 749..760
FT /note="Calmodulin-binding (IQ motif)"
FT /evidence="ECO:0000269|PubMed:11118454"
FT MOTIF 486..491
FT /note="GXGXXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 518..522
FT /note="GXSXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 653..655
FT /note="DGA/G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT ACT_SITE 520
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT ACT_SITE 653
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 396..451
FT /note="LITRKALLTLLKTVGADYHFPFIQGVSTEQSSAAGPHPFFSLDRTQPPTISL
FT NNLE -> Q (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:9111008"
FT /id="VSP_044365"
FT CONFLICT 24
FT /note="V -> A (in Ref. 1; AAC53136)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="V -> D (in Ref. 1; AAC53136)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="G -> D (in Ref. 1; AAC53136)"
FT /evidence="ECO:0000305"
FT CONFLICT 80
FT /note="A -> V (in Ref. 1; AAC53136)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="V -> E (in Ref. 1; AAC53136)"
FT /evidence="ECO:0000305"
FT CONFLICT 109
FT /note="Missing (in Ref. 1; AAC53136)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="S -> T (in Ref. 1; AAC53136)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="S -> T (in Ref. 1; AAC53136)"
FT /evidence="ECO:0000305"
FT CONFLICT 793
FT /note="H -> Y (in Ref. 1; AAC53136)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 807 AA; 89556 MW; 1B9018AE1B2D252F CRC64;
MQFFGRLVNT LSSVTNLFSN PFRVKEVSLA DYASSERVRE EGQLILLQNA SNRTWDCVLV
SPRNPQSGFR LFQLESEADA LVNFQQYSSQ LPPFYESSVQ VLHVEVLQHL TDLIRNHPSW
TVTHLAVELG IRECFHHSRI ISCANSTENE EGCTPLHLAC RKGDSEILVE LVQYCHAQMD
VTDNKGETAF HYAVQGDNPQ VLQLLGKNAS AGLNQVNNQG LTPLHLACQM GKQEMVRVLL
LCNARCNIMG PGGFPIHTAM KFSQKGCAEM IISMDSNQIH SKDPRYGASP LHWAKNAEMA
RMLLKRGCDV DSTSASGNTA LHVAVTRNRF DCVMVLLTYG ANAGARGEHG NTPLHLAMSK
DNMEMVKALI VFGAEVDTPN DFGETPAFIA SKISKLITRK ALLTLLKTVG ADYHFPFIQG
VSTEQSSAAG PHPFFSLDRT QPPTISLNNL ELQDLMPVSR ARKPAFILSS MRDEKRSHDH
LLCLDGGGVK GLVIIQLLIA IEKASGVATK DLFDWVAGTS TGGILALAIL HSKSMAYMRG
VYFRMKDEVF RGSRPYESGP LEEFLKREFG EHTKMTDVKK PKVMLTGTLS DRQPAELHLF
RNYDAPEAVR EPRCTPNINL KPPTQPADQL VWRAARSSGA APTYFRPNGR FLDGGLLANN
PTLDAMTEIH EYNQDMIRKG QGNKVKKLSI VVSLGTGKSP QVPVTCVDVF RPSNPWELAK
TVFGAKELGK MVVDCCTDPD GRAVDRARAW CEMVGIQYFR LNPQLGSDIM LDEVSDAVLV
NALWETEVYI YEHREEFQKL VQLLLSP
