PLPL9_MOUSE
ID PLPL9_MOUSE Reviewed; 807 AA.
AC P97819; Q99LA9; Q9JK61;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=85/88 kDa calcium-independent phospholipase A2;
DE Short=CaI-PLA2;
DE EC=3.1.1.4 {ECO:0000269|PubMed:18937505};
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 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 SHORT).
RC STRAIN=DBA/2J;
RX PubMed=9079688; DOI=10.1074/jbc.272.13.8576;
RA Balboa M.A., Balsinde J., Jones S.S., Dennis E.A.;
RT "Identity between the Ca2+-independent phospholipase A2 enzymes from P388D1
RT macrophages and Chinese hamster ovary cells.";
RL J. Biol. Chem. 272:8576-8580(1997).
RN [2]
RP SEQUENCE REVISION TO 2-3; 9; 11 AND 211.
RA Balboa M.A., Balsinde J., Jones S.S., Dennis E.A.;
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), ALTERNATIVE SPLICING, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=NIH Swiss;
RX PubMed=11563837; DOI=10.1006/bbrc.2001.5632;
RA Chiu C.-H., Jackowski S.;
RT "Role of calcium-independent phospholipases (iPLA(2)) in
RT phosphatidylcholine metabolism.";
RL Biochem. Biophys. Res. Commun. 287:600-606(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT).
RC STRAIN=C57BL/6J, FVB/N, and NMRI; TISSUE=Mammary tumor;
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 PROTEIN SEQUENCE OF 479-491, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Liver, Spleen, 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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=17895289; DOI=10.1152/ajpendo.00474.2007;
RA Bao S., Jacobson D.A., Wohltmann M., Bohrer A., Jin W., Philipson L.H.,
RA Turk J.;
RT "Glucose homeostasis, insulin secretion, and islet phospholipids in mice
RT that overexpress iPLA2beta in pancreatic beta-cells and in iPLA2beta-null
RT mice.";
RL Am. J. Physiol. 294:E217-E229(2008).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, ACTIVITY REGULATION, AND
RP DISRUPTION PHENOTYPE.
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 [9]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=18305254; DOI=10.1523/jneurosci.4354-07.2008;
RA Shinzawa K., Sumi H., Ikawa M., Matsuoka Y., Okabe M., Sakoda S.,
RA Tsujimoto Y.;
RT "Neuroaxonal dystrophy caused by group VIA phospholipase A2 deficiency in
RT mice: a model of human neurodegenerative disease.";
RL J. Neurosci. 28:2212-2220(2008).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=21813701; DOI=10.1523/jneurosci.0345-11.2011;
RA Beck G., Sugiura Y., Shinzawa K., Kato S., Setou M., Tsujimoto Y.,
RA Sakoda S., Sumi-Akamaru H.;
RT "Neuroaxonal dystrophy in calcium-independent phospholipase A2beta
RT deficiency results from insufficient remodeling and degeneration of
RT mitochondrial and presynaptic membranes.";
RL J. Neurosci. 31:11411-11420(2011).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
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). Hydrolyzes both saturated and unsaturated
CC long fatty acyl chains in various glycerophospholipid classes such as
CC phosphatidylcholines, phosphatidylethanolamines and phosphatidates,
CC with a preference for hydrolysis at sn-2 position. Can further
CC hydrolyze lysophospholipids carrying saturated fatty acyl chains
CC (lysophospholipase activity). Upon oxidative stress, contributes to
CC remodeling of mitochondrial phospholipids in pancreatic beta cells, in
CC a repair mechanism to reduce oxidized lipid content (By similarity).
CC Preferentially hydrolyzes oxidized polyunsaturated fatty acyl chains
CC from cardiolipins, yielding monolysocardiolipins that can be reacylated
CC with unoxidized fatty acyls to regenerate native cardiolipin species.
CC Hydrolyzes oxidized glycerophosphoethanolamines present in pancreatic
CC islets, releasing oxidized polyunsaturated fatty acids such as
CC hydroxyeicosatetraenoates (HETEs) (PubMed:24648512). Has thioesterase
CC activity toward fatty-acyl CoA releasing CoA-SH known to facilitate
CC fatty acid transport and beta-oxidation in mitochondria particularly in
CC skeletal muscle (PubMed:18937505). Plays a role in regulation of
CC membrane dynamics and homeostasis. Selectively hydrolyzes sn-2
CC arachidonoyl group in plasmalogen phospholipids, structural components
CC of lipid rafts and myelin (By similarity). Regulates F-actin
CC polymerization at the pseudopods, which is required for both speed and
CC directionality of MCP1/CCL2-induced monocyte chemotaxis (By
CC similarity). Targets membrane phospholipids to produce potent lipid
CC signaling messengers. Generates lysophosphatidate (LPA, 1-acyl-
CC glycerol-3-phosphate), which acts via G-protein receptors in various
CC cell types. Has phospholipase A2 activity toward platelet-activating
CC factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), likely
CC playing a role in inactivation of this potent pro-inflammatory
CC signaling lipid (By similarity). In response to glucose, amplifies
CC calcium influx in pancreatic beta cells to promote INS secretion
CC (PubMed:17895289). {ECO:0000250|UniProtKB:A0A3L7I2I8,
CC ECO:0000250|UniProtKB:O60733, ECO:0000269|PubMed:17895289,
CC ECO:0000269|PubMed:18937505, ECO:0000269|PubMed:24648512}.
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802;
CC Evidence={ECO:0000305|PubMed:18937505};
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812;
CC Evidence={ECO:0000305|PubMed:18937505};
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:0000269|PubMed:17895289};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40432;
CC Evidence={ECO:0000305|PubMed:17895289};
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:0000250|UniProtKB:P97570};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63257;
CC Evidence={ECO:0000250|UniProtKB:P97570};
CC -!- ACTIVITY REGULATION: Inhibited by calcium-activated calmodulin (By
CC similarity). Activated by ATP (PubMed:18937505, PubMed:17895289).
CC Inhibited by bromoenol lactone (BEL) (PubMed:18937505,
CC PubMed:17895289). {ECO:0000250|UniProtKB:P97570,
CC ECO:0000269|PubMed:17895289, ECO:0000269|PubMed:18937505}.
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:0000269|PubMed:11563837}. Cell
CC membrane {ECO:0000269|PubMed:11563837}. Mitochondrion
CC {ECO:0000269|PubMed:24648512}. 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; Synonyms=iPLA2-L;
CC IsoId=P97819-1; Sequence=Displayed;
CC Name=Short; Synonyms=iPLA2-S;
CC IsoId=P97819-2; Sequence=VSP_044364;
CC -!- TISSUE SPECIFICITY: Expressed in neurons of central and peripheral
CC nervous system (PubMed:18937505, PubMed:18305254). Highly expressed in
CC Purkinje cells in cerebellum and dorsal and ventral horn neurons in the
CC spinal cord (PubMed:18305254). Expressed in testis (at protein level)
CC (PubMed:18305254). Expressed in skeletal muscle (at protein level)
CC (PubMed:18937505). {ECO:0000269|PubMed:18305254,
CC ECO:0000269|PubMed:18937505}.
CC -!- DOMAIN: Has two putative calmodulin binding domains, the 1-9-14 and IQ
CC motifs. One calmodulin molecule interacts with PLA2G6 dimer, likely
CC through 1-9-14 motif on each monomer (By similarity). Binds calmodulin
CC in a calcium-dependent way (By similarity).
CC {ECO:0000250|UniProtKB:A0A3L7I2I8, ECO:0000250|UniProtKB:P97570}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice represent an appropriate model for
CC studying the pathogenesis of neuroaxonal dystrophy in human
CC neurodegenerative diseases (PubMed:18305254, PubMed:18937505). Mutant
CC mice show neuroaxonal dystrophy and significant motor dysfunction from
CC the age of 50 weeks that progressed to ataxia by 2 years
CC (PubMed:18305254). At 55 weeks they display numerous spheroids located
CC in the axons and synapses throughout central and peripheral nervous
CC system, mostly prominent in the tegmentum of the medulla, the lower
CC pons, and the dorsal horns of the spinal cord. Sciatic nerves have
CC reduced numbers of myelinated fibers indicative of neural degeneration
CC (PubMed:18305254). The neuroaxonal dystrophy is associated with
CC deficient remodeling of the mitochondrial inner membrane and
CC presynaptic membrane of axon terminals (PubMed:21813701). Mutant mice
CC gradually lose weight and die earlier than wild-type littermates
CC (PubMed:18305254). Mutant male mice show reduced fertility
CC (PubMed:18305254). {ECO:0000269|PubMed:18305254,
CC ECO:0000269|PubMed:18937505, ECO:0000269|PubMed:21813701}.
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DR EMBL; U88624; AAB48511.2; -; mRNA.
DR EMBL; AF259401; AAF72651.1; -; mRNA.
DR EMBL; BC003487; AAH03487.1; -; mRNA.
DR EMBL; BC057209; AAH57209.1; -; mRNA.
DR CCDS; CCDS27637.1; -. [P97819-2]
DR CCDS; CCDS56991.1; -. [P97819-1]
DR RefSeq; NP_001185952.1; NM_001199023.1. [P97819-1]
DR RefSeq; NP_001185953.1; NM_001199024.1. [P97819-2]
DR RefSeq; NP_001185954.1; NM_001199025.1. [P97819-2]
DR RefSeq; NP_058611.1; NM_016915.4. [P97819-2]
DR RefSeq; XP_006521215.1; XM_006521152.2. [P97819-1]
DR RefSeq; XP_006521216.1; XM_006521153.3. [P97819-1]
DR RefSeq; XP_006521217.1; XM_006521154.1. [P97819-1]
DR RefSeq; XP_006521218.1; XM_006521155.2. [P97819-1]
DR RefSeq; XP_006521219.1; XM_006521156.3. [P97819-1]
DR RefSeq; XP_006521220.1; XM_006521157.3. [P97819-1]
DR RefSeq; XP_006521221.1; XM_006521158.2. [P97819-1]
DR RefSeq; XP_006521222.1; XM_006521159.3. [P97819-1]
DR RefSeq; XP_006521223.1; XM_006521160.2. [P97819-1]
DR RefSeq; XP_017172187.1; XM_017316698.1. [P97819-2]
DR AlphaFoldDB; P97819; -.
DR SMR; P97819; -.
DR BioGRID; 207296; 1.
DR IntAct; P97819; 3.
DR STRING; 10090.ENSMUSP00000132071; -.
DR ChEMBL; CHEMBL3259503; -.
DR iPTMnet; P97819; -.
DR PhosphoSitePlus; P97819; -.
DR EPD; P97819; -.
DR MaxQB; P97819; -.
DR PaxDb; P97819; -.
DR PeptideAtlas; P97819; -.
DR PRIDE; P97819; -.
DR ProteomicsDB; 289936; -. [P97819-1]
DR ProteomicsDB; 289937; -. [P97819-2]
DR Antibodypedia; 225; 251 antibodies from 32 providers.
DR DNASU; 53357; -.
DR Ensembl; ENSMUST00000047816; ENSMUSP00000044234; ENSMUSG00000042632. [P97819-2]
DR Ensembl; ENSMUST00000166977; ENSMUSP00000132071; ENSMUSG00000042632. [P97819-2]
DR Ensembl; ENSMUST00000172403; ENSMUSP00000131081; ENSMUSG00000042632. [P97819-2]
DR Ensembl; ENSMUST00000173163; ENSMUSP00000134456; ENSMUSG00000042632. [P97819-2]
DR Ensembl; ENSMUST00000174021; ENSMUSP00000134672; ENSMUSG00000042632. [P97819-1]
DR GeneID; 53357; -.
DR KEGG; mmu:53357; -.
DR UCSC; uc007wtd.2; mouse. [P97819-1]
DR CTD; 8398; -.
DR MGI; MGI:1859152; Pla2g6.
DR VEuPathDB; HostDB:ENSMUSG00000042632; -.
DR eggNOG; KOG0513; Eukaryota.
DR GeneTree; ENSGT00940000158756; -.
DR HOGENOM; CLU_010817_0_0_1; -.
DR InParanoid; P97819; -.
DR OMA; MLAIEMH; -.
DR PhylomeDB; P97819; -.
DR TreeFam; TF319230; -.
DR Reactome; R-MMU-1482788; Acyl chain remodelling of PC.
DR Reactome; R-MMU-1482839; Acyl chain remodelling of PE.
DR Reactome; R-MMU-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-MMU-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR BioGRID-ORCS; 53357; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Pla2g6; mouse.
DR PRO; PR:P97819; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P97819; protein.
DR Bgee; ENSMUSG00000042632; Expressed in gastrula and 248 other tissues.
DR ExpressionAtlas; P97819; baseline and differential.
DR Genevisible; P97819; MM.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0047499; F:calcium-independent phospholipase A2 activity; IMP:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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; IMP:UniProtKB.
DR GO; GO:0102545; F:phosphatidyl phospholipase B activity; IEA:UniProtKB-EC.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0017171; F:serine hydrolase activity; IDA:MGI.
DR GO; GO:0019731; P:antibacterial humoral response; ISO:MGI.
DR GO; GO:0035965; P:cardiolipin acyl-chain remodeling; ISS:UniProtKB.
DR GO; GO:0032049; P:cardiolipin biosynthetic process; ISO:MGI.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR GO; GO:0007613; P:memory; ISO:MGI.
DR GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; ISO:MGI.
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; ISO:MGI.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0045921; P:positive regulation of exocytosis; ISO:MGI.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR GO; GO:0090037; P:positive regulation of protein kinase C signaling; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:1901339; P:regulation of store-operated calcium channel activity; ISO:MGI.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISO:MGI.
DR GO; GO:0014832; P:urinary bladder smooth muscle contraction; ISO:MGI.
DR GO; GO:0042311; P:vasodilation; ISO:MGI.
DR Gene3D; 1.25.40.20; -; 3.
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; 2.
DR Pfam; PF13606; Ank_3; 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; Direct protein sequencing;
KW Hydrolase; Lipid metabolism; Membrane; Mitochondrion;
KW Phospholipid metabolism; Phosphoprotein; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..807
FT /note="85/88 kDa calcium-independent phospholipase A2"
FT /id="PRO_0000067038"
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:0000250|UniProtKB:A0A3L7I2I8"
FT REGION 749..760
FT /note="Calmodulin-binding (IQ motif)"
FT /evidence="ECO:0000250|UniProtKB:A0A3L7I2I8"
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:0000250|UniProtKB:P97570"
FT VAR_SEQ 396..451
FT /note="LITRKALLTLLKTVGADHHFPIIQGVSTEQGSAAATHPLFSLDRTQPPAISL
FT NNLE -> Q (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9079688"
FT /id="VSP_044364"
SQ SEQUENCE 807 AA; 89560 MW; 3838889731100294 CRC64;
MQFFGRLVNT LSSVTNLFSN PFRVKEVSLT DYVSSERVRE EGQLILLQNV SNRTWDCVLV
SPRNPQSGFR LFQLESEADA LVNFQQFSSQ LPPFYESSVQ VLHVEVLQHL TDLIRNHPSW
TVTHLAVELG IRECFHHSRI ISCANSTENE EGCTPLHLAC RKGDSEILVE LVQYCHAQMD
VTDNKGETAF HYAVQGDNPQ VLQLLGKNAS AGLNQVNNQG LTPLHLACKM GKQEMVRVLL
LCNARCNIMG PGGFPIHTAM KFSQKGCAEM IISMDSNQIH SKDPRYGASP LHWAKNAEMA
RMLLKRGCDV DSTSSSGNTA LHVAVMRNRF DCVMVLLTYG ANAGARGEHG NTPLHLAMSK
DNMEMVKALI VFGAEVDTPN DFGETPALIA SKISKLITRK ALLTLLKTVG ADHHFPIIQG
VSTEQGSAAA THPLFSLDRT QPPAISLNNL ELQDLMPISR ARKPAFILSS MRDEKRSHDH
LLCLDGGGVK GLVIIQLLIA IEKASGVATK DLFDWVAGTS TGGILALAIL HSKSMAYMRG
VYFRMKDEVF RGSRPYESGP LEEFLKREFG EHTKMTDVKK PKVMLTGTLS DRQPAELHLF
RNYDAPEAVR EPRCNQNINL KPPTQPADQL VWRAARSSGA APTYFRPNGR FLDGGLLANN
PTLDAMTEIH EYNQDMIRKG QGNKVKKLSI VVSLGTGKSP QVPVTCVDVF RPSNPWELAK
TVFGAKELGK MVVDCCTDPD GRAVDRARAW CEMVGIQYFR LNPQLGSDIM LDEVSDAVLV
NALWETEVYI YEHREEFQKL VQLLLSP
