ID PA2G3_HUMAN Reviewed; 509 AA. AC Q9NZ20; O95768; DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 2. DT 24-JAN-2024, entry version 178. DE RecName: Full=Group 3 secretory phospholipase A2; DE EC=3.1.1.4 {ECO:0000269|PubMed:12522102, ECO:0000269|PubMed:18801741}; DE AltName: Full=Group III secretory phospholipase A2; DE Short=GIII sPLA2; DE Short=sPLA2-III; DE AltName: Full=Phosphatidylcholine 2-acylhydrolase 3; DE Flags: Precursor; GN Name=PLA2G3 {ECO:0000312|HGNC:HGNC:17934}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, AND VARIANT ALA-70. RX PubMed=10713052; DOI=10.1074/jbc.275.11.7492; RA Valentin E., Ghomashchi F., Gelb M.H., Lazdunski M., Lambeau G.; RT "Novel human secreted phospholipase A2 with homology to the group III bee RT venom enzyme."; RL J. Biol. Chem. 275:7492-7496(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-70. RC TISSUE=Brain; 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 [4] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, RP DOMAIN, AND MUTAGENESIS OF HIS-184. RX PubMed=12522102; DOI=10.1074/jbc.m211325200; RA Murakami M., Masuda S., Shimbara S., Bezzine S., Lazdunski M., Lambeau G., RA Gelb M.H., Matsukura S., Kokubu F., Adachi M., Kudo I.; RT "Cellular arachidonate-releasing function of novel classes of secretory RT phospholipase A2s (groups III and XII)."; RL J. Biol. Chem. 278:10657-10667(2003). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, PTM, TISSUE SPECIFICITY, INDUCTION, RP GLYCOSYLATION AT ASN-167 AND ASN-280, AND MUTAGENESIS OF ASN-167; HIS-184 RP AND ASN-280. RX PubMed=15863501; DOI=10.1074/jbc.m502088200; RA Murakami M., Masuda S., Shimbara S., Ishikawa Y., Ishii T., Kudo I.; RT "Cellular distribution, post-translational modification, and tumorigenic RT potential of human group III secreted phospholipase A(2)."; RL J. Biol. Chem. 280:24987-24998(2005). RN [6] RP FUNCTION, TISSUE SPECIFICITY, DOMAIN, AND MUTAGENESIS OF HIS-184. RX PubMed=17868035; DOI=10.1042/bj20070844; RA Masuda S., Yamamoto K., Hirabayashi T., Ishikawa Y., Ishii T., Kudo I., RA Murakami M.; RT "Human group III secreted phospholipase A2 promotes neuronal outgrowth and RT survival."; RL Biochem. J. 409:429-438(2008). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY. RX PubMed=18801741; DOI=10.1074/jbc.m804628200; RA Sato H., Kato R., Isogai Y., Saka G., Ohtsuki M., Taketomi Y., Yamamoto K., RA Tsutsumi K., Yamada J., Masuda S., Ishikawa Y., Ishii T., Kobayashi T., RA Ikeda K., Taguchi R., Hatakeyama S., Hara S., Kudo I., Itabe H., RA Murakami M.; RT "Analyses of group III secreted phospholipase A2 transgenic mice reveal RT potential participation of this enzyme in plasma lipoprotein modification, RT macrophage foam cell formation, and atherosclerosis."; RL J. Biol. Chem. 283:33483-33497(2008). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=20393563; DOI=10.1038/nature08895; RA Kim J., Lee J.E., Heynen-Genel S., Suyama E., Ono K., Lee K., Ideker T., RA Aza-Blanc P., Gleeson J.G.; RT "Functional genomic screen for modulators of ciliogenesis and cilium RT length."; RL Nature 464:1048-1051(2010). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND MUTAGENESIS OF RP HIS-184. RX PubMed=23624557; DOI=10.1038/ni.2586; RA Taketomi Y., Ueno N., Kojima T., Sato H., Murase R., Yamamoto K., RA Tanaka S., Sakanaka M., Nakamura M., Nishito Y., Kawana M., Kambe N., RA Ikeda K., Taguchi R., Nakamizo S., Kabashima K., Gelb M.H., Arita M., RA Yokomizo T., Nakamura M., Watanabe K., Hirai H., Nakamura M., Okayama Y., RA Ra C., Aritake K., Urade Y., Morimoto K., Sugimoto Y., Shimizu T., RA Narumiya S., Hara S., Murakami M.; RT "Mast cell maturation is driven via a group III phospholipase A2- RT prostaglandin D2-DP1 receptor paracrine axis."; RL Nat. Immunol. 14:554-563(2013). RN [11] RP FUNCTION. RX PubMed=28947740; DOI=10.1038/s41598-017-12434-z; RA Murase R., Taketomi Y., Miki Y., Nishito Y., Saito M., Fukami K., RA Yamamoto K., Murakami M.; RT "Group III phospholipase A2 promotes colitis and colorectal cancer."; RL Sci. Rep. 7:12261-12261(2017). CC -!- FUNCTION: Secretory calcium-dependent phospholipase A2 that primarily CC targets extracellular phospholipids. Hydrolyzes the ester bond of the CC fatty acyl group attached at sn-2 position of phospholipids without CC apparent head group selectivity (PubMed:12522102, PubMed:18801741, CC PubMed:15863501, PubMed:28947740). Contributes to phospholipid CC remodeling of low-density lipoprotein (LDL) and high-density CC lipoprotein (HDL) particles. Hydrolyzes LDL phospholipids releasing CC unsaturated fatty acids that regulate macrophage differentiation toward CC foam cells (PubMed:18801741). May act in an autocrine and paracrine CC manner (PubMed:23624557). Secreted by immature mast cells, acts on CC nearby fibroblasts upstream to PTDGS to synthesize prostaglandin D2 CC (PGD2), which in turn promotes mast cell maturation and degranulation CC via PTGDR (PubMed:23624557). Secreted by epididymal epithelium, acts on CC immature sperm cells within the duct, modulating the degree of CC unsaturation of the fatty acyl components of phosphatidylcholines CC required for acrosome assembly and sperm cell motility. Facilitates the CC replacement of fatty acyl chains in phosphatidylcholines in sperm CC membranes from omega-6 and omega-9 to omega-3 polyunsaturated fatty CC acids (PUFAs). Coupled to lipoxygenase pathway, may process omega-6 CC PUFAs to generate oxygenated lipid mediators in the male reproductive CC tract (By similarity). At pericentrosomal preciliary compartment, CC negatively regulates ciliogenesis likely by regulating endocytotic CC recycling of ciliary membrane protein (PubMed:20393563). Coupled to CC cyclooxygenase pathway provides arachidonate to generate prostaglandin CC E2 (PGE2), a potent immunomodulatory lipid in inflammation and CC tumorigenesis (PubMed:12522102, PubMed:15863501). At colonic epithelial CC barrier, preferentially hydrolyzes phospholipids having arachidonate CC and docosahexaenoate at sn-2 position, contributing to the generation CC of oxygenated metabolites involved in colonic stem cell homeostasis CC (PubMed:28947740). Releases C16:0 and C18:0 lysophosphatidylcholine CC subclasses from neuron plasma membranes and promotes neurite outgrowth CC and neuron survival (PubMed:17868035). {ECO:0000250|UniProtKB:Q8BZT7, CC ECO:0000269|PubMed:12522102, ECO:0000269|PubMed:15863501, CC ECO:0000269|PubMed:17868035, ECO:0000269|PubMed:18801741, CC ECO:0000269|PubMed:20393563, ECO:0000269|PubMed:23624557, CC ECO:0000269|PubMed:28947740}. 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:12522102, ECO:0000269|PubMed:18801741}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802; CC Evidence={ECO:0000305|PubMed:12522102, ECO:0000305|PubMed:18801741}; 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:12522102}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812; CC Evidence={ECO:0000305|PubMed:12522102}; 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:0000269|PubMed:12522102}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40428; CC Evidence={ECO:0000305|PubMed:12522102}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3- CC phosphoethanolamine + H2O = (9Z,12Z)-octadecadienoate + 1- CC hexadecanoyl-sn-glycero-3-phosphoethanolamine + H(+); CC Xref=Rhea:RHEA:40815, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30245, ChEBI:CHEBI:73004, ChEBI:CHEBI:73008; CC Evidence={ECO:0000269|PubMed:12522102, ECO:0000269|PubMed:15863501, CC ECO:0000269|PubMed:18801741, ECO:0000269|PubMed:23624557}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40816; CC Evidence={ECO:0000305|PubMed:12522102, ECO:0000305|PubMed:15863501, CC ECO:0000305|PubMed:18801741, ECO:0000305|PubMed:23624557}; 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:12522102}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40432; CC Evidence={ECO:0000305|PubMed:12522102}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000250|UniProtKB:P00630}; CC Note=Binds 1 Ca(2+) ion. {ECO:0000250|UniProtKB:P00630}; CC -!- ACTIVITY REGULATION: Arachidonic acid release is markedly increased by CC glypican, a glycosylphosphatidylinositol-anchored heparan sulfate CC proteoglycan. {ECO:0000269|PubMed:12522102}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12522102}. Cell CC membrane {ECO:0000269|PubMed:12522102}. Cytoplasm, cytoskeleton, CC microtubule organizing center, centrosome, centriole CC {ECO:0000269|PubMed:20393563}. Recycling endosome CC {ECO:0000269|PubMed:20393563}. Note=Localized at pericentrosomal CC preciliary compartment. {ECO:0000269|PubMed:20393563}. CC -!- TISSUE SPECIFICITY: Expressed in kidney, heart, liver, and skeletal CC muscle. Also present in placenta and peripheral blood leukocytes. Not CC detected in colon, thymus, spleen and small intestine. In lung, CC expressed in bronchial epithelial cells and alveolar macrophages, but CC scarcely detected in alveolar epithelium, arterial walls and CC interstitial fibroblasts (at protein level). In joints of CC osteoarthritis and rheumatoid arthritis, expressed in endothelial cells CC (at protein level). In normal heart, detected in some vessels. In CC myocardial tissues with acute infarction, expressed in vascular CC endothelial cells adjacent to cardiomyocytes and those in lesions with CC granulation. Expression in cardiomyocytes is scarce (at protein level). CC In uterus, breast and colon cancers, detected in tumor cells and CC neighboring microvascular endothelium, but not in normal glandular CC tissues (at protein level) (PubMed:15863501). Expressed in dermal CC resting mast cells (at protein level) and pulmonary mast cells CC (PubMed:23624557). Expressed in neuronal fibers (at protein level) CC (PubMed:17868035). Highly expressed in dorsal root ganglia neurons (at CC protein level) (PubMed:17868035). Expressed in Purkinje cells in CC cerebellum (at protein level) (PubMed:17868035). In stomach is CC preferentially expressed in neuronal fibers and in microvascular CC endothelium (PubMed:17868035). Sparsely expressed in normal aorta (at CC protein level). Highly expressed in macrophages and smooth muscle cells CC in aorta with atheroma (PubMed:18801741). {ECO:0000269|PubMed:15863501, CC ECO:0000269|PubMed:17868035, ECO:0000269|PubMed:18801741, CC ECO:0000269|PubMed:23624557}. CC -!- INDUCTION: By IL1B/interleukin-1 beta and TNF in microvascular CC endothelial cells (at protein level). {ECO:0000269|PubMed:15863501}. CC -!- DOMAIN: The phospholipase A2-like domain represents the fully processed CC form after N- and C-termini are cleaved off. It is the secreted mature CC form found in biological fluids. {ECO:0000269|PubMed:12522102, CC ECO:0000269|PubMed:15863501, ECO:0000269|PubMed:17868035}. CC -!- PTM: N-glycosylation does not affect the catalytic activity, but is CC required for proper secretion. A nonglycosylated form is observed in CC several cell types. {ECO:0000269|PubMed:15863501}. CC -!- PTM: In several cell types, the N- and C-termini are cleaved off. CC {ECO:0000305|PubMed:15863501}. CC -!- SIMILARITY: Belongs to the phospholipase A2 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD15617.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF220490; AAF44746.1; -; mRNA. DR EMBL; AC005005; AAD15617.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC025316; AAH25316.1; -; mRNA. DR CCDS; CCDS13889.1; -. DR RefSeq; NP_056530.2; NM_015715.4. DR AlphaFoldDB; Q9NZ20; -. DR SMR; Q9NZ20; -. DR BioGRID; 119074; 30. DR IntAct; Q9NZ20; 3. DR STRING; 9606.ENSP00000215885; -. DR BindingDB; Q9NZ20; -. DR ChEMBL; CHEMBL4667; -. DR SwissLipids; SLP:000001086; -. DR GlyCosmos; Q9NZ20; 5 sites, No reported glycans. DR GlyGen; Q9NZ20; 5 sites. DR iPTMnet; Q9NZ20; -. DR PhosphoSitePlus; Q9NZ20; -. DR BioMuta; PLA2G3; -. DR DMDM; 317373314; -. DR EPD; Q9NZ20; -. DR MassIVE; Q9NZ20; -. DR PaxDb; 9606-ENSP00000215885; -. DR PeptideAtlas; Q9NZ20; -. DR ProteomicsDB; 83316; -. DR Antibodypedia; 11027; 217 antibodies from 24 providers. DR DNASU; 50487; -. DR Ensembl; ENST00000215885.4; ENSP00000215885.3; ENSG00000100078.4. DR GeneID; 50487; -. DR KEGG; hsa:50487; -. DR MANE-Select; ENST00000215885.4; ENSP00000215885.3; NM_015715.5; NP_056530.2. DR UCSC; uc003aka.4; human. DR AGR; HGNC:17934; -. DR CTD; 50487; -. DR DisGeNET; 50487; -. DR GeneCards; PLA2G3; -. DR HGNC; HGNC:17934; PLA2G3. DR HPA; ENSG00000100078; Tissue enhanced (esophagus, skin, vagina). DR MIM; 611651; gene. DR neXtProt; NX_Q9NZ20; -. DR OpenTargets; ENSG00000100078; -. DR PharmGKB; PA38267; -. DR VEuPathDB; HostDB:ENSG00000100078; -. DR eggNOG; ENOG502QTYI; Eukaryota. DR GeneTree; ENSGT00940000161662; -. DR HOGENOM; CLU_535922_0_0_1; -. DR InParanoid; Q9NZ20; -. DR OMA; TRFQQCL; -. DR OrthoDB; 2963555at2759; -. DR PhylomeDB; Q9NZ20; -. DR TreeFam; TF324679; -. DR PathwayCommons; Q9NZ20; -. DR Reactome; R-HSA-1482788; Acyl chain remodelling of PC. DR Reactome; R-HSA-1482839; Acyl chain remodelling of PE. DR Reactome; R-HSA-1482925; Acyl chain remodelling of PG. DR SignaLink; Q9NZ20; -. DR BioGRID-ORCS; 50487; 6 hits in 1148 CRISPR screens. DR GenomeRNAi; 50487; -. DR Pharos; Q9NZ20; Tbio. DR PRO; PR:Q9NZ20; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q9NZ20; Protein. DR Bgee; ENSG00000100078; Expressed in gingival epithelium and 90 other cell types or tissues. DR GO; GO:0005814; C:centriole; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB. DR GO; GO:0047498; F:calcium-dependent phospholipase A2 activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0001675; P:acrosome assembly; IEA:Ensembl. DR GO; GO:0050482; P:arachidonic acid secretion; IEA:InterPro. DR GO; GO:0048469; P:cell maturation; IEA:Ensembl. DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB. DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IDA:UniProtKB. DR GO; GO:0019372; P:lipoxygenase pathway; IEA:Ensembl. DR GO; GO:0034374; P:low-density lipoprotein particle remodeling; IDA:UniProtKB. DR GO; GO:0042116; P:macrophage activation; IEA:Ensembl. DR GO; GO:0043303; P:mast cell degranulation; IEA:UniProtKB-KW. DR GO; GO:1900222; P:negative regulation of amyloid-beta clearance; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:MGI. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB. DR GO; GO:0046473; P:phosphatidic acid metabolic process; IDA:UniProtKB. DR GO; GO:0046470; P:phosphatidylcholine metabolic process; IDA:UniProtKB. DR GO; GO:0046337; P:phosphatidylethanolamine metabolic process; IDA:UniProtKB. DR GO; GO:0046471; P:phosphatidylglycerol metabolic process; IDA:UniProtKB. DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IDA:UniProtKB. DR GO; GO:0006658; P:phosphatidylserine metabolic process; IDA:UniProtKB. DR GO; GO:0006644; P:phospholipid metabolic process; TAS:ProtInc. DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IEA:Ensembl. DR GO; GO:1903595; P:positive regulation of histamine secretion by mast cell; IDA:UniProtKB. DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IDA:UniProtKB. DR GO; GO:0060376; P:positive regulation of mast cell differentiation; IEA:Ensembl. DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB. DR GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; IDA:UniProtKB. DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; IEA:Ensembl. DR GO; GO:0002532; P:production of molecular mediator involved in inflammatory response; IEA:Ensembl. DR GO; GO:2001135; P:regulation of endocytic recycling; IMP:UniProtKB. DR GO; GO:0007288; P:sperm axoneme assembly; IEA:Ensembl. DR CDD; cd04704; PLA2_bee_venom_like; 1. DR CDD; cd04705; PLA2_group_III_like; 1. DR Gene3D; 1.20.90.10; Phospholipase A2 domain; 2. DR InterPro; IPR016090; PLipase_A2_dom. DR InterPro; IPR036444; PLipase_A2_dom_sf. DR InterPro; IPR033113; PLipase_A2_His_AS. DR PANTHER; PTHR12253:SF19; GROUP 3 SECRETORY PHOSPHOLIPASE A2; 1. DR PANTHER; PTHR12253; RH14732P; 1. DR Pfam; PF05826; Phospholip_A2_2; 2. DR SUPFAM; SSF48619; Phospholipase A2, PLA2; 2. DR PROSITE; PS00118; PA2_HIS; 1. DR Genevisible; Q9NZ20; HS. PE 1: Evidence at protein level; KW Calcium; Cell membrane; Cilium biogenesis/degradation; Cytoplasm; KW Cytoskeleton; Disulfide bond; Endosome; Glycoprotein; Hydrolase; KW Lipid metabolism; Mast cell degranulation; Membrane; Metal-binding; KW Phospholipid metabolism; Reference proteome; Secreted; Signal. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..509 FT /note="Group 3 secretory phospholipase A2" FT /evidence="ECO:0000255" FT /id="PRO_0000022992" FT REGION 123..149 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 150..291 FT /note="Phospholipase A2-like" FT /evidence="ECO:0000269|PubMed:12522102, FT ECO:0000269|PubMed:15863501, ECO:0000269|PubMed:17868035" FT REGION 283..354 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 458..482 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 302..317 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 184 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10035" FT ACT_SITE 214 FT /evidence="ECO:0000250|UniProtKB:P00630" FT BINDING 158 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P00630" FT BINDING 160 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P00630" FT BINDING 162 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P00630" FT BINDING 185 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P00630" FT CARBOHYD 167 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:15863501" FT CARBOHYD 280 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:15863501" FT CARBOHYD 325 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 396 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 439 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 159..181 FT /evidence="ECO:0000250|UniProtKB:P00630" FT DISULFID 180..220 FT /evidence="ECO:0000250|UniProtKB:P00630" FT DISULFID 187..213 FT /evidence="ECO:0000250|UniProtKB:P00630" FT DISULFID 211..244 FT /evidence="ECO:0000250|UniProtKB:P00630" FT VARIANT 70 FT /note="S -> A (in dbSNP:rs2232176)" FT /evidence="ECO:0000269|PubMed:10713052, FT ECO:0000269|PubMed:15489334" FT /id="VAR_024555" FT VARIANT 116 FT /note="E -> Q (in dbSNP:rs2074734)" FT /id="VAR_024556" FT VARIANT 157 FT /note="L -> V (in dbSNP:rs2074735)" FT /id="VAR_020288" FT VARIANT 307 FT /note="H -> Y (in dbSNP:rs2232180)" FT /id="VAR_056581" FT VARIANT 322 FT /note="S -> R (in dbSNP:rs2072193)" FT /id="VAR_024557" FT VARIANT 378 FT /note="R -> Q (in dbSNP:rs2232183)" FT /id="VAR_034366" FT MUTAGEN 167 FT /note="N->S: Loss of glycosylation." FT /evidence="ECO:0000269|PubMed:15863501" FT MUTAGEN 184 FT /note="H->Q: Impairs PGE2 synthesis. Impairs PGD2 FT synthesis. Impairs mast cell degranulation. Impairs neurite FT outgrowth." FT /evidence="ECO:0000269|PubMed:12522102, FT ECO:0000269|PubMed:15863501, ECO:0000269|PubMed:17868035, FT ECO:0000269|PubMed:23624557" FT MUTAGEN 280 FT /note="N->S: Loss of glycosylation." FT /evidence="ECO:0000269|PubMed:15863501" SQ SEQUENCE 509 AA; 57167 MW; ED03BED129B0BC9F CRC64; MGVQAGLFGM LGFLGVALGG SPALRWYRTS CHLTKAVPGN PLGYLSFLAK DAQGLALIHA RWDAHRRLQS CSWEDEPELT AAYGALCAHE TAWGSFIHTP GPELQRALAT LQSQWEACRA LEESPAGARK KRAAGQSGVP GGGHQREKRG WTMPGTLWCG VGDSAGNSSE LGVFQGPDLC CREHDRCPQN ISPLQYNYGI RNYRFHTISH CDCDTRFQQC LQNQHDSISD IVGVAFFNVL EIPCFVLEEQ EACVAWYWWG GCRMYGTVPL ARLQPRTFYN ASWSSRATSP TPSSRSPAPP KPRQKQHLRK GPPHQKGSKR PSKANTTALQ DPMVSPRLDV APTGLQGPQG GLKPQGARWV CRSFRRHLDQ CEHQIGPREI EFQLLNSAQE PLFHCNCTRR LARFLRLHSP PEVTNMLWEL LGTTCFKLAP PLDCVEGKNC SRDPRAIRVS ARHLRRLQQR RHQLQDKGTD ERQPWPSEPL RGPMSFYNQC LQLTQAARRP DRQQKSWSQ //