ID   PA24A_MOUSE             Reviewed;         748 AA.
AC   P47713;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 199.
DE   RecName: Full=Cytosolic phospholipase A2;
DE            Short=cPLA2;
DE   AltName: Full=Phospholipase A2 group IVA;
DE   Includes:
DE     RecName: Full=Phospholipase A2;
DE              EC=3.1.1.4 {ECO:0000269|PubMed:1904318};
DE     AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE   Includes:
DE     RecName: Full=Lysophospholipase;
DE              EC=3.1.1.5 {ECO:0000250|UniProtKB:P47712};
GN   Name=Pla2g4a; Synonyms=Cpla2, Pla2g4;
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], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
RP   ACTIVITY REGULATION.
RX   PubMed=1904318; DOI=10.1016/0092-8674(91)90556-e;
RA   Clark J.D., Lin L.-L., Kriz R.W., Ramesha C.S., Sultzman L.A., Lin A.Y.,
RA   Milona N., Knopf J.L.;
RT   "A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-
RT   dependent translocation domain with homology to PKC and GAP.";
RL   Cell 65:1043-1051(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   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   [3]
RP   DISRUPTION PHENOTYPE, FUNCTION, AND PATHWAY.
RX   PubMed=9403692; DOI=10.1038/37622;
RA   Uozumi N., Kume K., Nagase T., Nakatani N., Ishii S., Tashiro F.,
RA   Komagata Y., Maki K., Ikuta K., Ouchi Y., Miyazaki J., Shimizu T.;
RT   "Role of cytosolic phospholipase A2 in allergic response and parturition.";
RL   Nature 390:618-622(1997).
RN   [4]
RP   DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX   PubMed=9403693; DOI=10.1038/37635;
RA   Bonventre J.V., Huang Z., Taheri M.R., O'Leary E., Li E., Moskowitz M.A.,
RA   Sapirstein A.;
RT   "Reduced fertility and postischaemic brain injury in mice deficient in
RT   cytosolic phospholipase A2.";
RL   Nature 390:622-625(1997).
RN   [5]
RP   PHOSPHORYLATION AT SER-505 AND SER-726, AND ACTIVITY REGULATION.
RX   PubMed=10978317; DOI=10.1074/jbc.m003395200;
RA   Hefner Y., Boersch-Haubold A.G., Murakami M., Wilde J.I., Pasquet S.,
RA   Schieltz D., Ghomashchi F., Yates J.R. III, Armstrong C.G., Paterson A.,
RA   Cohen P., Fukunaga R., Hunter T., Kudo I., Watson S.P., Gelb M.H.;
RT   "Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by
RT   MNK1-related protein kinases.";
RL   J. Biol. Chem. 275:37542-37551(2000).
RN   [6]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=11984592; DOI=10.1038/nm0502-480;
RA   Nagase T., Uozumi N., Ishii S., Kita Y., Yamamoto H., Ohga E., Ouchi Y.,
RA   Shimizu T.;
RT   "A pivotal role of cytosolic phospholipase A(2) in bleomycin-induced
RT   pulmonary fibrosis.";
RL   Nat. Med. 8:480-484(2002).
RN   [7]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=16172261; DOI=10.1084/jem.20050665;
RA   Marusic S., Leach M.W., Pelker J.W., Azoitei M.L., Uozumi N., Cui J.,
RA   Shen M.W., DeClercq C.M., Miyashiro J.S., Carito B.A., Thakker P.,
RA   Simmons D.L., Leonard J.P., Shimizu T., Clark J.D.;
RT   "Cytosolic phospholipase A2 alpha-deficient mice are resistant to
RT   experimental autoimmune encephalomyelitis.";
RL   J. Exp. Med. 202:841-851(2005).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-437, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA   Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA   Thibault P.;
RT   "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL   Immunity 30:143-154(2009).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435; SER-437; SER-505;
RP   SER-726 AND SER-728, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Heart, Kidney, Lung, 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).
CC   -!- FUNCTION: Has primarily calcium-dependent phospholipase and
CC       lysophospholipase activities, with a major role in membrane lipid
CC       remodeling and biosynthesis of lipid mediators of the inflammatory
CC       response (PubMed:1904318, PubMed:9403692, PubMed:9403693). Plays an
CC       important role in embryo implantation and parturition through its
CC       ability to trigger prostanoid production (PubMed:9403692,
CC       PubMed:9403693). Preferentially hydrolyzes the ester bond of the fatty
CC       acyl group attached at sn-2 position of phospholipids (phospholipase A2
CC       activity). Selectively hydrolyzes sn-2 arachidonoyl group from membrane
CC       phospholipids, providing the precursor for eicosanoid biosynthesis via
CC       the cyclooxygenase pathway. In an alternative pathway of eicosanoid
CC       biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid
CC       lysophopholipids to release free bioactive eicosanoids. Hydrolyzes the
CC       ester bond of the fatty acyl group attached at sn-1 position of
CC       phospholipids (phospholipase A1 activity) only if an ether linkage
CC       rather than an ester linkage is present at the sn-2 position. This
CC       hydrolysis is not stereospecific. Has calcium-independent phospholipase
CC       A2 and lysophospholipase activities in the presence of
CC       phosphoinositides. Has O-acyltransferase activity. Catalyzes the
CC       transfer of fatty acyl chains from phospholipids to a primary hydroxyl
CC       group of glycerol (sn-1 or sn-3), potentially contributing to
CC       monoacylglycerol synthesis (By similarity).
CC       {ECO:0000250|UniProtKB:P47712, ECO:0000269|PubMed:1904318,
CC       ECO:0000269|PubMed:9403692, ECO:0000269|PubMed:9403693}.
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:1904318};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802;
CC         Evidence={ECO:0000305|PubMed:1904318};
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:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15178;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
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:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40428;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1,2-di-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-
CC         phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-
CC         (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H(+);
CC         Xref=Rhea:RHEA:41075, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:32395, ChEBI:CHEBI:60657, ChEBI:CHEBI:74344;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41076;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
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:0000269|PubMed:9403693};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40520;
CC         Evidence={ECO:0000305|PubMed:9403693};
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:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-octadecanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-
CC         phosphocholine + H2O = (9Z,12Z,15Z)-octadecatrienoate + 1-
CC         octadecanoyl-sn-glycero-3-phosphocholine + H(+);
CC         Xref=Rhea:RHEA:41307, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:32387, ChEBI:CHEBI:73858, ChEBI:CHEBI:78022;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41308;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-hexadecanoyl-sn-glycero-
CC         3-phosphocholine + H2O = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-
CC         glycero-3-phosphocholine + H(+) + hexadecanoate;
CC         Xref=Rhea:RHEA:41071, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:74344, ChEBI:CHEBI:77694;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41072;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
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:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41068;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1'-sn-glycerol)
CC         + H2O = (9Z)-octadecenoate + 1-(9Z-octadecenoyl)-sn-glycero-3-
CC         phospho-(1'-sn-glycerol) + H(+); Xref=Rhea:RHEA:41123,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC         ChEBI:CHEBI:72828, ChEBI:CHEBI:75163;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41124;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC         3-phosphate + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-
CC         octadecanoyl-sn-glycero-3-phosphate + H(+); Xref=Rhea:RHEA:40451,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395,
CC         ChEBI:CHEBI:74565, ChEBI:CHEBI:77091;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40452;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
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:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(prostaglandin E2)-sn-glycero-3-phosphoethanolamine + H2O =
CC         H(+) + prostaglandin E2 + sn-glycero-3-phosphoethanolamine;
CC         Xref=Rhea:RHEA:53704, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:137581, ChEBI:CHEBI:143890, ChEBI:CHEBI:606564;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53705;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-[(15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-sn-glycero-
CC         3-phosphocholine + H2O = (15S)-hydroxy-(5Z,8Z,11Z,13E)-
CC         eicosatetraenoate + H(+) + sn-glycerol 3-phosphocholine;
CC         Xref=Rhea:RHEA:53700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16870, ChEBI:CHEBI:57409, ChEBI:CHEBI:137584;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53701;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-[(15R)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-sn-glycero-
CC         3-phosphocholine + H2O = (15R)-hydroxy-(5Z,8Z,11Z,13E)-
CC         eicosatetraenoate + H(+) + sn-glycerol 3-phosphocholine;
CC         Xref=Rhea:RHEA:53696, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16870, ChEBI:CHEBI:78837, ChEBI:CHEBI:137583;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53697;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(prostaglandin E2)-sn-glycero-3-phosphocholine + H2O = H(+)
CC         + prostaglandin E2 + sn-glycerol 3-phosphocholine;
CC         Xref=Rhea:RHEA:53692, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16870, ChEBI:CHEBI:137585, ChEBI:CHEBI:606564;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53693;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-[(11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoyl]-sn-glycero-
CC         3-phosphocholine + H2O = (11R)-hydroxy-(5Z,8Z,12E,14Z)-
CC         eicosatetraenoate + H(+) + sn-glycerol 3-phosphocholine;
CC         Xref=Rhea:RHEA:53688, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16870, ChEBI:CHEBI:78836, ChEBI:CHEBI:137582;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53689;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-O-hexadecyl-sn-glycero-3-
CC         phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 2-O-
CC         hexadecyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:41271,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395,
CC         ChEBI:CHEBI:77695, ChEBI:CHEBI:77696;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41272;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC         3-phosphocholine + glycerol = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
CC         glycerol + 1-octadecanoyl-sn-glycero-3-phosphocholine;
CC         Xref=Rhea:RHEA:41099, ChEBI:CHEBI:17754, ChEBI:CHEBI:73858,
CC         ChEBI:CHEBI:74965, ChEBI:CHEBI:75612;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41100;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-octadecanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-
CC         phosphocholine + glycerol = 1-(9Z,12Z,15Z-octadecatrienoyl)-glycerol
CC         + 1-octadecanoyl-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:41087,
CC         ChEBI:CHEBI:17754, ChEBI:CHEBI:73858, ChEBI:CHEBI:75610,
CC         ChEBI:CHEBI:78022; Evidence={ECO:0000250|UniProtKB:P47712};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41088;
CC         Evidence={ECO:0000250|UniProtKB:P47712};
CC   -!- ACTIVITY REGULATION: Activated by cytosolic calcium, which is necessary
CC       for binding to membrane lipids (PubMed:1904318). Activated by
CC       phosphorylation in response to mitogenic stimuli (PubMed:10978317).
CC       Stimulated by agonists such as ATP and thrombin (PubMed:10978317).
CC       {ECO:0000269|PubMed:10978317, ECO:0000269|PubMed:1904318}.
CC   -!- PATHWAY: Membrane lipid metabolism; glycerophospholipid metabolism.
CC       {ECO:0000269|PubMed:1904318}.
CC   -!- PATHWAY: Lipid metabolism; arachidonate metabolism.
CC       {ECO:0000269|PubMed:9403692}.
CC   -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC       {ECO:0000269|PubMed:9403692}.
CC   -!- PATHWAY: Lipid metabolism; leukotriene B4 biosynthesis.
CC       {ECO:0000250|UniProtKB:P47712}.
CC   -!- SUBUNIT: Interacts with KAT5. {ECO:0000250|UniProtKB:P47712}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P47712}. Golgi
CC       apparatus membrane {ECO:0000250|UniProtKB:P47712}. Nucleus envelope
CC       {ECO:0000250|UniProtKB:P47712}. Note=Translocates to intracellular
CC       membranes in a calcium-dependent way. {ECO:0000250|UniProtKB:P47712}.
CC   -!- TISSUE SPECIFICITY: Expressed in various organs including uterus,
CC       kidney, spleen, liver, heart, lung and brain (at protein level).
CC       {ECO:0000269|PubMed:9403693}.
CC   -!- DOMAIN: The N-terminal C2 domain associates with lipid membranes upon
CC       calcium binding. It modulates enzyme activity by presenting the active
CC       site to its substrate in response to elevations of cytosolic calcium.
CC       In the presence of phosphoinositides, regulates phospholipase A2 and
CC       lysophospholipase activities in a calcium-independent way.
CC       {ECO:0000250|UniProtKB:P47712}.
CC   -!- PTM: Phosphorylated at both Ser-505 and Ser-726 in response to
CC       mitogenic stimuli. {ECO:0000269|PubMed:10978317}.
CC   -!- DISRUPTION PHENOTYPE: Mutant female mice have reduced fertility and
CC       produce small litters that most commonly result in dead pups. The
CC       pregnancy failure is likely due to a deficient implantation and
CC       parturition (PubMed:9403693, PubMed:9403692). In an inflammatory
CC       setting, mutant mice are protected against various pathological changes
CC       (PubMed:9403692, PubMed:9403693, PubMed:11984592, PubMed:16172261). In
CC       a bleomycin-induced model of pulmonary fibrosis, mutant mice show an
CC       attenuated lung inflammation characterized by impaired induction of
CC       eicosanoid synthesis and impaired inflammatory leukocyte migration to
CC       the lung (PubMed:11984592). Mutant mice are resistant to experimental
CC       autoimmune encephalomyelitis due to impaired T helper 1 type immune
CC       response (PubMed:16172261). They are also partially protected against
CC       cerebral ischaemia and reperfusion (PubMed:9403693). In a systemic
CC       anaphylaxis model, mutant mice show reduced allergen-induced bronchial
CC       hyperactivity (PubMed:9403692). {ECO:0000269|PubMed:11984592,
CC       ECO:0000269|PubMed:16172261, ECO:0000269|PubMed:9403692,
CC       ECO:0000269|PubMed:9403693}.
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DR   EMBL; M72394; AAB00796.1; -; mRNA.
DR   EMBL; BC003816; AAH03816.1; -; mRNA.
DR   CCDS; CCDS15352.1; -.
DR   PIR; B39898; B39898.
DR   RefSeq; NP_032895.1; NM_008869.4.
DR   AlphaFoldDB; P47713; -.
DR   BMRB; P47713; -.
DR   SMR; P47713; -.
DR   BioGRID; 202222; 13.
DR   IntAct; P47713; 13.
DR   MINT; P47713; -.
DR   STRING; 10090.ENSMUSP00000070868; -.
DR   BindingDB; P47713; -.
DR   ChEMBL; CHEMBL2907; -.
DR   iPTMnet; P47713; -.
DR   PhosphoSitePlus; P47713; -.
DR   SwissPalm; P47713; -.
DR   jPOST; P47713; -.
DR   PaxDb; 10090-ENSMUSP00000070868; -.
DR   PeptideAtlas; P47713; -.
DR   ProteomicsDB; 294369; -.
DR   Pumba; P47713; -.
DR   Antibodypedia; 4104; 460 antibodies from 38 providers.
DR   DNASU; 18783; -.
DR   Ensembl; ENSMUST00000070200.15; ENSMUSP00000070868.9; ENSMUSG00000056220.15.
DR   GeneID; 18783; -.
DR   KEGG; mmu:18783; -.
DR   UCSC; uc007cxt.2; mouse.
DR   AGR; MGI:1195256; -.
DR   CTD; 5321; -.
DR   MGI; MGI:1195256; Pla2g4a.
DR   VEuPathDB; HostDB:ENSMUSG00000056220; -.
DR   eggNOG; KOG1012; Eukaryota.
DR   eggNOG; KOG1325; Eukaryota.
DR   GeneTree; ENSGT01030000234606; -.
DR   HOGENOM; CLU_011663_1_1_1; -.
DR   InParanoid; P47713; -.
DR   OMA; NFMRGLS; -.
DR   OrthoDB; 4250045at2759; -.
DR   PhylomeDB; P47713; -.
DR   TreeFam; TF325228; -.
DR   BRENDA; 3.1.1.4; 3474.
DR   Reactome; R-MMU-111995; phospho-PLA2 pathway.
DR   Reactome; R-MMU-1482788; Acyl chain remodelling of PC.
DR   Reactome; R-MMU-1482798; Acyl chain remodeling of CL.
DR   Reactome; R-MMU-1482801; Acyl chain remodelling of PS.
DR   Reactome; R-MMU-1482839; Acyl chain remodelling of PE.
DR   Reactome; R-MMU-1482922; Acyl chain remodelling of PI.
DR   Reactome; R-MMU-1482925; Acyl chain remodelling of PG.
DR   Reactome; R-MMU-1483115; Hydrolysis of LPC.
DR   Reactome; R-MMU-1483166; Synthesis of PA.
DR   Reactome; R-MMU-2142753; Arachidonic acid metabolism.
DR   Reactome; R-MMU-418592; ADP signalling through P2Y purinoceptor 1.
DR   Reactome; R-MMU-432142; Platelet sensitization by LDL.
DR   Reactome; R-MMU-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR   SABIO-RK; P47713; -.
DR   UniPathway; UPA00383; -.
DR   UniPathway; UPA00662; -.
DR   UniPathway; UPA00878; -.
DR   UniPathway; UPA00940; -.
DR   BioGRID-ORCS; 18783; 2 hits in 62 CRISPR screens.
DR   PRO; PR:P47713; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; P47713; Protein.
DR   Bgee; ENSMUSG00000056220; Expressed in indifferent gonad and 244 other cell types or tissues.
DR   ExpressionAtlas; P47713; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR   GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR   GO; GO:0042588; C:zymogen granule; ISO:MGI.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR   GO; GO:0047498; F:calcium-dependent phospholipase A2 activity; IMP:UniProtKB.
DR   GO; GO:0005544; F:calcium-dependent phospholipid binding; ISS:UniProtKB.
DR   GO; GO:0047499; F:calcium-independent phospholipase A2 activity; ISO:MGI.
DR   GO; GO:1902387; F:ceramide 1-phosphate binding; ISS:UniProtKB.
DR   GO; GO:0035035; F:histone acetyltransferase binding; ISO:MGI.
DR   GO; GO:0004622; F:lysophospholipase activity; ISS:UniProtKB.
DR   GO; GO:0008374; F:O-acyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0102545; F:phosphatidyl phospholipase B activity; IEA:UniProtKB-EC.
DR   GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; ISS:UniProtKB.
DR   GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISS:UniProtKB.
DR   GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; ISS:UniProtKB.
DR   GO; GO:0004623; F:phospholipase A2 activity; IDA:UniProtKB.
DR   GO; GO:0019369; P:arachidonic acid metabolic process; ISS:UniProtKB.
DR   GO; GO:0050482; P:arachidonic acid secretion; IDA:UniProtKB.
DR   GO; GO:0071236; P:cellular response to antibiotic; IDA:MGI.
DR   GO; GO:0046697; P:decidualization; ISO:MGI.
DR   GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR   GO; GO:0006071; P:glycerol metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0046475; P:glycerophospholipid catabolic process; IBA:GO_Central.
DR   GO; GO:0046456; P:icosanoid biosynthetic process; IMP:MGI.
DR   GO; GO:0019370; P:leukotriene biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0006640; P:monoacylglycerol biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0001542; P:ovulation from ovarian follicle; ISO:MGI.
DR   GO; GO:0036151; P:phosphatidylcholine acyl-chain remodeling; ISO:MGI.
DR   GO; GO:0034638; P:phosphatidylcholine catabolic process; IMP:UniProtKB.
DR   GO; GO:0034478; P:phosphatidylglycerol catabolic process; ISS:UniProtKB.
DR   GO; GO:0006663; P:platelet activating factor biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:0043032; P:positive regulation of macrophage activation; IMP:UniProtKB.
DR   GO; GO:0010572; P:positive regulation of platelet activation; ISO:MGI.
DR   GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; ISO:MGI.
DR   GO; GO:0032308; P:positive regulation of prostaglandin secretion; IMP:MGI.
DR   GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; IMP:UniProtKB.
DR   GO; GO:0031340; P:positive regulation of vesicle fusion; ISO:MGI.
DR   GO; GO:0001516; P:prostaglandin biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI.
DR   GO; GO:0051592; P:response to calcium ion; ISO:MGI.
DR   GO; GO:0010033; P:response to organic substance; ISO:MGI.
DR   GO; GO:0043129; P:surfactant homeostasis; ISO:MGI.
DR   CDD; cd04036; C2_cPLA2; 1.
DR   CDD; cd07200; cPLA2_Grp-IVA; 1.
DR   Gene3D; 2.60.40.150; C2 domain; 1.
DR   Gene3D; 3.40.1090.10; Cytosolic phospholipase A2 catalytic domain; 1.
DR   InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR   InterPro; IPR041847; C2_cPLA2.
DR   InterPro; IPR000008; C2_dom.
DR   InterPro; IPR035892; C2_domain_sf.
DR   InterPro; IPR002642; LysoPLipase_cat_dom.
DR   PANTHER; PTHR10728; CYTOSOLIC PHOSPHOLIPASE A2; 1.
DR   PANTHER; PTHR10728:SF13; CYTOSOLIC PHOSPHOLIPASE A2; 1.
DR   Pfam; PF00168; C2; 1.
DR   Pfam; PF01735; PLA2_B; 1.
DR   SMART; SM00239; C2; 1.
DR   SMART; SM00022; PLAc; 1.
DR   SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR   SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR   PROSITE; PS50004; C2; 1.
DR   PROSITE; PS51210; PLA2C; 1.
DR   Genevisible; P47713; MM.
PE   1: Evidence at protein level;
KW   Calcium; Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism;
KW   Glycerol metabolism; Golgi apparatus; Hydrolase; Isopeptide bond;
KW   Leukotriene biosynthesis; Lipid biosynthesis; Lipid degradation;
KW   Lipid metabolism; Lipid-binding; Membrane; Metal-binding; Nucleus;
KW   Phospholipid degradation; Phospholipid metabolism; Phosphoprotein;
KW   Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW   Ubl conjugation.
FT   CHAIN           1..748
FT                   /note="Cytosolic phospholipase A2"
FT                   /id="PRO_0000187263"
FT   DOMAIN          6..122
FT                   /note="C2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          140..739
FT                   /note="PLA2c"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00555"
FT   REGION          1..178
FT                   /note="Phospholipid binding"
FT                   /evidence="ECO:0000305"
FT   REGION          427..458
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        427..457
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        228
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        548
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         40
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         40
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         41
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         43
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         43
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         65
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         93
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         94
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         95
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P47712"
FT   MOD_RES         268
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P47712"
FT   MOD_RES         434
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P50393"
FT   MOD_RES         435
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         437
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19144319,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         505
FT                   /note="Phosphoserine; by MAPK"
FT                   /evidence="ECO:0000269|PubMed:10978317,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         515
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P50393"
FT   MOD_RES         726
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:10978317,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         728
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   CROSSLNK        540
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P47712"
FT   CROSSLNK        605
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P47712"
SQ   SEQUENCE   748 AA;  85222 MW;  49D12BBB2911492A CRC64;
     MSFIDPYQHI IVEHQYSHKF TVVVLRATKV TKGTFGDMLD TPDPYVELFI STTPDSRKRT
     RHFNNDINPV WNETFEFILD PNQENVLEIT LMDANYVMDE TLGTATFPVS SMKVGEKKEV
     PFIFNQVTEM ILEMSLEVCS CPDLRFSMAL CDQEKTFRQQ RKENIKENMK KLLGPKKSEG
     LYSTRDVPVV AILGSGGGFR AMVGFSGVMK ALYESGILDC ATYIAGLSGS TWYMSTLYSH
     PDFPEKGPEE INEELMKNVS HNPLLLLTPQ KVKRYVESLW KKKSSGQPVT FTDIFGMLIG
     ETLIQNRMSM TLSSLKEKVN AARCPLPLFT CLHVKPDVSE LMFADWVEFS PYEIGMAKYG
     TFMAPDLFGS KFFMGTVVKK YEENPLHFLM GVWGSAFSIL FNRVLGVSGS QNKGSTMEEE
     LENITAKHIV SNDSSDSDDE AQGPKGTENE EAEKEYQSDN QASWVHRMLM ALVSDSALFN
     TREGRAGKVH NFMLGLNLNT SYPLSPLRDF SSQDSFDDEL DAAVADPDEF ERIYEPLDVK
     SKKIHVVDSG LTFNLPYPLI LRPQRGVDLI ISFDFSARPS DTSPPFKELL LAEKWAKMNK
     LPFPKIDPYV FDREGLKECY VFKPKNPDVE KDCPTIIHFV LANINFRKYK APGVLRETKE
     EKEIADFDIF DDPESPFSTF NFQYPNQAFK RLHDLMYFNT LNNIDVIKDA IVESIEYRRQ
     NPSRCSVSLS NVEARKFFNK EFLSKPTV
//