PLPL9_HUMAN
ID PLPL9_HUMAN Reviewed; 806 AA.
AC O60733; A8K597; B0QYE8; O75645; Q8N452; Q9UG29; Q9UIT0; Q9Y671;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=85/88 kDa calcium-independent phospholipase A2;
DE Short=CaI-PLA2;
DE EC=3.1.1.4 {ECO:0000269|PubMed:20886109};
DE AltName: Full=2-lysophosphatidylcholine acylhydrolase;
DE EC=3.1.1.5 {ECO:0000269|PubMed:20886109};
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:20886109};
DE AltName: Full=Patatin-like phospholipase domain-containing protein 9;
DE Short=PNPLA9;
GN Name=PLA2G6; Synonyms=PLPLA9;
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] (ISOFORMS LH-IPLA2; ANKYRIN-IPLA2-1 AND
RP ANKYRIN-IPLA2-2), AND FUNCTION.
RC TISSUE=B-cell, and Testis;
RX PubMed=9417066; DOI=10.1074/jbc.273.1.207;
RA Larsson P.K.A., Claesson H.-E., Kennedy B.P.;
RT "Multiple splice variants of the human calcium-independent phospholipase A2
RT and their effect on enzyme activity.";
RL J. Biol. Chem. 273:207-214(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS LH-IPLA2 AND SH-IPLA2),
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RC TISSUE=Pancreatic islet;
RX PubMed=10092647; DOI=10.1074/jbc.274.14.9607;
RA Ma Z., Wang X., Nowatzke W., Ramanadham S., Turk J.;
RT "Human pancreatic islets express mRNA species encoding two distinct
RT catalytically active isoforms of group VI phospholipase A2 (iPLA2) that
RT arise from an exon-skipping mechanism of alternative splicing of the
RT transcript from the iPLA2 gene on chromosome 22q13.1.";
RL J. Biol. Chem. 274:9607-9616(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND FUNCTION.
RX PubMed=10336645; DOI=10.1046/j.1432-1327.1999.00418.x;
RA Larsson Forsell P.K.A., Kennedy B.P., Claesson H.-E.;
RT "The human calcium-independent phospholipase A2 gene. Multiple enzymes with
RT distinct properties from a single gene.";
RL Eur. J. Biochem. 262:575-585(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LH-IPLA2).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LH-IPLA2).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-58; GLY-63; GLN-70;
RP ASN-183 AND THR-343.
RG NIEHS SNPs program;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LH-IPLA2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LH-IPLA2 AND SH-IPLA2).
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 [11]
RP FUNCTION IN CHEMOTAXIS, AND SUBCELLULAR LOCATION.
RX PubMed=18208975; DOI=10.1084/jem.20071243;
RA Mishra R.S., Carnevale K.A., Cathcart M.K.;
RT "iPLA2beta: front and center in human monocyte chemotaxis to MCP-1.";
RL J. Exp. Med. 205:347-359(2008).
RN [12]
RP REVIEW ON FAMILY.
RX PubMed=19029121; DOI=10.1194/jlr.r800082-jlr200;
RA Kienesberger P.C., Oberer M., Lass A., Zechner R.;
RT "Mammalian patatin domain containing proteins: a family with diverse
RT lipolytic activities involved in multiple biological functions.";
RL J. Lipid Res. 50:S63-S68(2009).
RN [13]
RP FUNCTION, AND PHARMACEUTICAL USE.
RX PubMed=19164547; DOI=10.1073/pnas.0811224106;
RA Malhotra A., Edelman-Novemsky I., Xu Y., Plesken H., Ma J., Schlame M.,
RA Ren M.;
RT "Role of calcium-independent phospholipase A2 in the pathogenesis of Barth
RT syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:2337-2341(2009).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, VARIANTS THR-341; CYS-517; TRP-632; ARG-638;
RP VAL-691 DEL; GLN-741; TRP-741; TRP-747 AND STOP-790, AND MUTAGENESIS OF
RP SER-519.
RX PubMed=20886109; DOI=10.1371/journal.pone.0012897;
RA Engel L.A., Jing Z., O'Brien D.E., Sun M., Kotzbauer P.T.;
RT "Catalytic function of PLA2G6 is impaired by mutations associated with
RT infantile neuroaxonal dystrophy but not dystonia-parkinsonism.";
RL PLoS ONE 5:e12897-e12897(2010).
RN [15]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23533611; DOI=10.1371/journal.pone.0059267;
RA Hsu Y.H., Dumlao D.S., Cao J., Dennis E.A.;
RT "Assessing phospholipase A2 activity toward cardiolipin by mass
RT spectrometry.";
RL PLoS ONE 8:E59267-E59267(2013).
RN [16]
RP VARIANT NBIA2A VAL-691 DEL.
RX PubMed=17033970; DOI=10.1086/508572;
RA Khateeb S., Flusser H., Ofir R., Shelef I., Narkis G., Vardi G., Shorer Z.,
RA Levy R., Galil A., Elbedour K., Birk O.S.;
RT "PLA2G6 mutation underlies infantile neuroaxonal dystrophy.";
RL Am. J. Hum. Genet. 79:942-948(2006).
RN [17]
RP VARIANTS NBIA2B THR-545; TRP-632 AND VAL-691 DEL, AND VARIANTS NBIA2A
RP GLU-310; THR-341; CYS-517; ARG-638; TRP-741 AND STOP-790.
RX PubMed=16783378; DOI=10.1038/ng1826;
RA Morgan N.V., Westaway S.K., Morton J.E., Gregory A., Gissen P., Sonek S.,
RA Cangul H., Coryell J., Canham N., Nardocci N., Zorzi G., Pasha S.,
RA Rodriguez D., Desguerre I., Mubaidin A., Bertini E., Trembath R.C.,
RA Simonati A., Schanen C., Johnson C.A., Levinson B., Woods C.G., Wilmot B.,
RA Kramer P., Gitschier J., Maher E.R., Hayflick S.J.;
RT "PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative
RT disorders with high brain iron.";
RL Nat. Genet. 38:752-754(2006).
RN [18]
RP ERRATUM.
RA Morgan N.V., Westaway S.K., Morton J.E., Gregory A., Gissen P., Sonek S.,
RA Cangul H., Coryell J., Canham N., Nardocci N., Zorzi G., Pasha S.,
RA Rodriguez D., Desguerre I., Mubaidin A., Bertini E., Trembath R.C.,
RA Simonati A., Schanen C., Johnson C.A., Levinson B., Woods C.G., Wilmot B.,
RA Kramer P., Gitschier J., Maher E.R., Hayflick S.J.;
RL Nat. Genet. 38:957-957(2006).
RN [19]
RP VARIANTS PARK14 GLN-741 AND TRP-747.
RX PubMed=18570303; DOI=10.1002/ana.21415;
RA Paisan-Ruiz C., Bhatia K.P., Li A., Hernandez D., Davis M., Wood N.W.,
RA Hardy J., Houlden H., Singleton A., Schneider S.A.;
RT "Characterization of PLA2G6 as a locus for dystonia-parkinsonism.";
RL Ann. Neurol. 65:19-23(2009).
RN [20]
RP VARIANTS NBIA2A GLY-484 AND MET-661.
RX PubMed=23749988; DOI=10.1136/jmedgenet-2013-101634;
RA Koeroglu C., Seven M., Tolun A.;
RT "Recessive truncating NALCN mutation in infantile neuroaxonal dystrophy
RT with facial dysmorphism.";
RL J. Med. Genet. 50:515-520(2013).
RN [21]
RP VARIANT TRP-550.
RX PubMed=28887846; DOI=10.1002/humu.23335;
RA Zhou X.L., He L.X., Yu L.J., Wang Y., Wang X.J., Wang E.D., Yang T.;
RT "Mutations in KARS cause early-onset hearing loss and leukoencephalopathy:
RT Potential pathogenic mechanism.";
RL Hum. Mutat. 38:1740-1750(2017).
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:9417066, PubMed:10092647, PubMed:10336645,
CC PubMed:20886109). Hydrolyzes both saturated and unsaturated long fatty
CC acyl chains in various glycerophospholipid classes such as
CC phosphatidylcholines, phosphatidylethanolamines and phosphatidates,
CC with a preference for hydrolysis at sn-2 position (PubMed:10092647,
CC PubMed:10336645, PubMed:20886109). Can further hydrolyze
CC lysophospholipids carrying saturated fatty acyl chains
CC (lysophospholipase activity) (PubMed:20886109). Upon oxidative stress,
CC contributes to remodeling of mitochondrial phospholipids in pancreatic
CC beta cells, in a repair mechanism to reduce oxidized lipid content
CC (PubMed:23533611). Preferentially hydrolyzes oxidized polyunsaturated
CC fatty acyl chains from cardiolipins, yielding monolysocardiolipins that
CC can be reacylated with unoxidized fatty acyls to regenerate native
CC cardiolipin species (By similarity). Hydrolyzes oxidized
CC glycerophosphoethanolamines present in pancreatic islets, releasing
CC oxidized polyunsaturated fatty acids such as hydroxyeicosatetraenoates
CC (HETEs) (By similarity). 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:20886109). 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 (PubMed:18208975). Targets
CC membrane phospholipids to produce potent lipid signaling messengers.
CC Generates lysophosphatidate (LPA, 1-acyl-glycerol-3-phosphate), which
CC acts via G-protein receptors in various cell types (By similarity). Has
CC phospholipase A2 activity toward platelet-activating factor (PAF, 1-O-
CC alkyl-2-acetyl-sn-glycero-3-phosphocholine), likely playing a role in
CC inactivation of this potent pro-inflammatory signaling lipid (By
CC similarity). In response to glucose, amplifies calcium influx in
CC pancreatic beta cells to promote INS secretion (By similarity).
CC {ECO:0000250|UniProtKB:A0A3L7I2I8, ECO:0000250|UniProtKB:P97570,
CC ECO:0000250|UniProtKB:P97819, ECO:0000269|PubMed:10092647,
CC ECO:0000269|PubMed:10336645, ECO:0000269|PubMed:18208975,
CC ECO:0000269|PubMed:20886109, ECO:0000269|PubMed:23533611,
CC ECO:0000269|PubMed:9417066}.
CC -!- FUNCTION: [Isoform Ankyrin-iPLA2-1]: Lacks the catalytic domain and may
CC act as a negative regulator of the catalytically active isoforms.
CC {ECO:0000269|PubMed:9417066}.
CC -!- FUNCTION: [Isoform Ankyrin-iPLA2-2]: Lacks the catalytic domain and may
CC act as a negative regulator of the catalytically active isoforms.
CC {ECO:0000269|PubMed:9417066}.
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:20886109};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802;
CC Evidence={ECO:0000305|PubMed:20886109};
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:0000269|PubMed:20886109};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38780;
CC Evidence={ECO:0000305|PubMed:20886109};
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:A0A3L7I2I8,
CC ECO:0000250|UniProtKB:P97819};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8,
CC ECO:0000250|UniProtKB:P97819};
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:10092647, ECO:0000269|PubMed:23533611};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40428;
CC Evidence={ECO:0000305|PubMed:10092647, ECO:0000305|PubMed:23533611};
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:A0A3L7I2I8,
CC ECO:0000250|UniProtKB:P97819};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40432;
CC Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8,
CC 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:0000269|PubMed:20886109};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15178;
CC Evidence={ECO:0000305|PubMed:20886109};
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:0000269|PubMed:20886109};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC Evidence={ECO:0000305|PubMed:20886109};
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:20886109};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646;
CC Evidence={ECO:0000305|PubMed:20886109};
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:0000269|PubMed:23533611};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40464;
CC Evidence={ECO:0000305|PubMed:23533611};
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:0000269|PubMed:23533611};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40468;
CC Evidence={ECO:0000305|PubMed:23533611};
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:0000250|UniProtKB:P97819};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:52814;
CC Evidence={ECO:0000250|UniProtKB:P97819};
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: Activated by ATP (PubMed:10092647). Inhibited by
CC calcium-activated calmodulin (By similarity). Inhibited by bromoenol
CC lactone (BEL) (By similarity). {ECO:0000250|UniProtKB:P97570,
CC ECO:0000269|PubMed:10092647}.
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 -!- INTERACTION:
CC O60733; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-12089905, EBI-742887;
CC O60733; Q9NZL9: MAT2B; NbExp=3; IntAct=EBI-12089905, EBI-10317491;
CC O60733; Q8N1F7: NUP93; NbExp=3; IntAct=EBI-12089905, EBI-1042703;
CC O60733; O60733: PLA2G6; NbExp=3; IntAct=EBI-12089905, EBI-12089905;
CC O60733; O95199: RCBTB2; NbExp=3; IntAct=EBI-12089905, EBI-742404;
CC O60733; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-12089905, EBI-6257312;
CC O60733; Q14140: SERTAD2; NbExp=3; IntAct=EBI-12089905, EBI-2822051;
CC O60733; Q86XT4: TRIM50; NbExp=3; IntAct=EBI-12089905, EBI-9867283;
CC O60733; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-12089905, EBI-11975223;
CC O60733; B2RXF5: ZBTB42; NbExp=3; IntAct=EBI-12089905, EBI-12287587;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18208975}. Cell
CC membrane {ECO:0000269|PubMed:18208975}. Mitochondrion
CC {ECO:0000250|UniProtKB:P97819}. Cell projection, pseudopodium
CC {ECO:0000269|PubMed:18208975}. Note=Recruited to the membrane-enriched
CC pseudopods upon MCP1/CCL2 stimulation in monocytes.
CC {ECO:0000269|PubMed:18208975}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=LH-iPLA2;
CC IsoId=O60733-1; Sequence=Displayed;
CC Name=SH-iPLA2;
CC IsoId=O60733-2; Sequence=VSP_000278;
CC Name=Ankyrin-iPLA2-1;
CC IsoId=O60733-3; Sequence=VSP_000281, VSP_000282;
CC Name=Ankyrin-iPLA2-2;
CC IsoId=O60733-4; Sequence=VSP_000277, VSP_000279, VSP_000280;
CC -!- TISSUE SPECIFICITY: Four different transcripts were found to be
CC expressed in a distinct tissue distribution.
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 -!- DISEASE: Neurodegeneration with brain iron accumulation 2B (NBIA2B)
CC [MIM:610217]: A neurodegenerative disorder associated with iron
CC accumulation in the brain, primarily in the basal ganglia. It is
CC characterized by progressive extrapyramidal dysfunction leading to
CC rigidity, dystonia, dysarthria and sensorimotor impairment.
CC {ECO:0000269|PubMed:16783378}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neurodegeneration with brain iron accumulation 2A (NBIA2A)
CC [MIM:256600]: A neurodegenerative disease characterized by pathologic
CC axonal swelling and spheroid bodies in the central nervous system.
CC Onset is within the first 2 years of life with death by age 10 years.
CC {ECO:0000269|PubMed:16783378, ECO:0000269|PubMed:17033970,
CC ECO:0000269|PubMed:23749988}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Parkinson disease 14 (PARK14) [MIM:612953]: An adult-onset
CC progressive neurodegenerative disorder characterized by parkinsonism,
CC dystonia, severe cognitive decline, cerebral and cerebellar atrophy and
CC absent iron in the basal ganglia on magnetic resonance imaging.
CC {ECO:0000269|PubMed:18570303}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- PHARMACEUTICAL: Potential target for therapeutic intervention of Barth
CC syndrome.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/pla2g6/";
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DR EMBL; AF064594; AAC97486.1; -; mRNA.
DR EMBL; AF102988; AAD41722.1; -; mRNA.
DR EMBL; AF102989; AAD41723.1; -; mRNA.
DR EMBL; AF117692; AAD30424.1; -; Genomic_DNA.
DR EMBL; AF117677; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117678; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117679; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117680; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117681; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117682; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117683; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117684; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117685; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117686; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117687; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117688; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117689; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117690; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF117691; AAD30424.1; JOINED; Genomic_DNA.
DR EMBL; AF116267; AAF34728.1; -; Genomic_DNA.
DR EMBL; AF116252; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116253; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116254; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116255; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116256; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116257; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116258; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116259; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116260; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116261; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116262; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116263; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116264; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116265; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AF116266; AAF34728.1; JOINED; Genomic_DNA.
DR EMBL; AL080187; CAB45768.2; -; mRNA.
DR EMBL; CR456543; CAG30429.1; -; mRNA.
DR EMBL; AY522921; AAR92478.1; -; Genomic_DNA.
DR EMBL; AK291212; BAF83901.1; -; mRNA.
DR EMBL; AL022322; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW60219.1; -; Genomic_DNA.
DR EMBL; CH471095; EAW60220.1; -; Genomic_DNA.
DR EMBL; BC036742; AAH36742.2; -; mRNA.
DR EMBL; BC051904; AAH51904.1; -; mRNA.
DR CCDS; CCDS13967.1; -. [O60733-1]
DR CCDS; CCDS33645.1; -. [O60733-2]
DR RefSeq; NP_001004426.1; NM_001004426.1. [O60733-2]
DR RefSeq; NP_001186491.1; NM_001199562.1. [O60733-2]
DR RefSeq; NP_003551.2; NM_003560.2. [O60733-1]
DR RefSeq; XP_005261821.1; XM_005261764.2.
DR RefSeq; XP_005261822.1; XM_005261765.1.
DR RefSeq; XP_005261823.1; XM_005261766.1.
DR RefSeq; XP_006724395.1; XM_006724332.3.
DR RefSeq; XP_016884470.1; XM_017028981.1.
DR RefSeq; XP_016884471.1; XM_017028982.1.
DR RefSeq; XP_016884477.1; XM_017028988.1.
DR AlphaFoldDB; O60733; -.
DR SMR; O60733; -.
DR BioGRID; 113986; 28.
DR IntAct; O60733; 11.
DR MINT; O60733; -.
DR STRING; 9606.ENSP00000333142; -.
DR BindingDB; O60733; -.
DR ChEMBL; CHEMBL3213; -.
DR DrugBank; DB01103; Quinacrine.
DR SwissLipids; SLP:000000618; -.
DR iPTMnet; O60733; -.
DR PhosphoSitePlus; O60733; -.
DR BioMuta; PLA2G6; -.
DR EPD; O60733; -.
DR MassIVE; O60733; -.
DR MaxQB; O60733; -.
DR PaxDb; O60733; -.
DR PeptideAtlas; O60733; -.
DR PRIDE; O60733; -.
DR ProteomicsDB; 49578; -. [O60733-1]
DR ProteomicsDB; 49579; -. [O60733-2]
DR ProteomicsDB; 49580; -. [O60733-3]
DR ProteomicsDB; 49581; -. [O60733-4]
DR Antibodypedia; 225; 251 antibodies from 32 providers.
DR DNASU; 8398; -.
DR Ensembl; ENST00000332509.8; ENSP00000333142.3; ENSG00000184381.20. [O60733-1]
DR Ensembl; ENST00000335539.7; ENSP00000335149.3; ENSG00000184381.20. [O60733-2]
DR Ensembl; ENST00000402064.5; ENSP00000386100.1; ENSG00000184381.20. [O60733-2]
DR Ensembl; ENST00000660610.1; ENSP00000499555.1; ENSG00000184381.20. [O60733-1]
DR Ensembl; ENST00000663895.1; ENSP00000499712.1; ENSG00000184381.20. [O60733-1]
DR Ensembl; ENST00000667521.1; ENSP00000499665.1; ENSG00000184381.20. [O60733-1]
DR GeneID; 8398; -.
DR KEGG; hsa:8398; -.
DR MANE-Select; ENST00000332509.8; ENSP00000333142.3; NM_003560.4; NP_003551.2.
DR UCSC; uc003auy.2; human. [O60733-1]
DR CTD; 8398; -.
DR DisGeNET; 8398; -.
DR GeneCards; PLA2G6; -.
DR GeneReviews; PLA2G6; -.
DR HGNC; HGNC:9039; PLA2G6.
DR HPA; ENSG00000184381; Low tissue specificity.
DR MalaCards; PLA2G6; -.
DR MIM; 256600; phenotype.
DR MIM; 603604; gene.
DR MIM; 610217; phenotype.
DR MIM; 612953; phenotype.
DR neXtProt; NX_O60733; -.
DR OpenTargets; ENSG00000184381; -.
DR Orphanet; 199351; Adult-onset dystonia-parkinsonism.
DR Orphanet; 35069; Infantile neuroaxonal dystrophy.
DR PharmGKB; PA33367; -.
DR VEuPathDB; HostDB:ENSG00000184381; -.
DR eggNOG; KOG0513; Eukaryota.
DR GeneTree; ENSGT00940000158756; -.
DR HOGENOM; CLU_010817_0_0_1; -.
DR InParanoid; O60733; -.
DR OMA; KGDVECL; -.
DR OrthoDB; 841851at2759; -.
DR PhylomeDB; O60733; -.
DR TreeFam; TF319230; -.
DR BRENDA; 3.1.1.4; 2681.
DR PathwayCommons; O60733; -.
DR Reactome; R-HSA-1482788; Acyl chain remodelling of PC.
DR Reactome; R-HSA-1482798; Acyl chain remodeling of CL.
DR Reactome; R-HSA-1482839; Acyl chain remodelling of PE.
DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-HSA-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR SignaLink; O60733; -.
DR BioGRID-ORCS; 8398; 7 hits in 1077 CRISPR screens.
DR ChiTaRS; PLA2G6; human.
DR GeneWiki; PLA2G6; -.
DR GenomeRNAi; 8398; -.
DR Pharos; O60733; Tchem.
DR PRO; PR:O60733; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; O60733; protein.
DR Bgee; ENSG00000184381; Expressed in right uterine tube and 156 other tissues.
DR ExpressionAtlas; O60733; baseline and differential.
DR Genevisible; O60733; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
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; IEA:Ensembl.
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:0016787; F:hydrolase activity; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004622; F:lysophospholipase activity; IDA: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:ProtInc.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0017171; F:serine hydrolase activity; IEA:Ensembl.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0035965; P:cardiolipin acyl-chain remodeling; IDA:UniProtKB.
DR GO; GO:0032049; P:cardiolipin biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; IEA:Ensembl.
DR GO; GO:0046473; P:phosphatidic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0034638; P:phosphatidylcholine catabolic process; IDA: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; IEA:Ensembl.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; IBA:GO_Central.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0045921; P:positive regulation of exocytosis; IEA:Ensembl.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0090037; P:positive regulation of protein kinase C signaling; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IEA:Ensembl.
DR GO; GO:1901339; P:regulation of store-operated calcium channel activity; IEA:Ensembl.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IEA:Ensembl.
DR GO; GO:0014832; P:urinary bladder smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
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; Disease variant; Dystonia;
KW Hydrolase; Lipid metabolism; Membrane; Mitochondrion; Neurodegeneration;
KW Parkinson disease; Parkinsonism; Pharmaceutical; Phospholipid metabolism;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..806
FT /note="85/88 kDa calcium-independent phospholipase A2"
FT /id="PRO_0000067037"
FT TRANSMEM 480..500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 511..531
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 481..665
FT /note="PNPLA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT REGION 677..686
FT /note="Calmodulin-binding (1-9-14 motif)"
FT /evidence="ECO:0000250|UniProtKB:A0A3L7I2I8"
FT REGION 748..759
FT /note="Calmodulin-binding (IQ motif)"
FT /evidence="ECO:0000250|UniProtKB:A0A3L7I2I8"
FT MOTIF 485..490
FT /note="GXGXXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 517..521
FT /note="GXSXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 652..654
FT /note="DGA/G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT ACT_SITE 519
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT ACT_SITE 652
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT VAR_SEQ 71..142
FT /note="Missing (in isoform Ankyrin-iPLA2-2)"
FT /evidence="ECO:0000303|PubMed:9417066"
FT /id="VSP_000277"
FT VAR_SEQ 396..450
FT /note="LVTRKAILTLLRTVGAEYCFPPIHGVPAEQGSAAPHHPFSLERAQPPPISLN
FT NLE -> Q (in isoform SH-iPLA2)"
FT /evidence="ECO:0000303|PubMed:10092647,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_000278"
FT VAR_SEQ 450..499
FT /note="ELQDLMHISRARKPAFILGSMRDEKRTHDHLLCLDGGGVKGLIIIQLLIA
FT -> GSHPSQAGWWAWGAVSDGTTGSHAHLTGPEASVHPGLHEGREADMQNLSP (in
FT isoform Ankyrin-iPLA2-2)"
FT /evidence="ECO:0000303|PubMed:9417066"
FT /id="VSP_000279"
FT VAR_SEQ 477..479
FT /note="HDH -> CRT (in isoform Ankyrin-iPLA2-1)"
FT /evidence="ECO:0000303|PubMed:9417066"
FT /id="VSP_000281"
FT VAR_SEQ 480..806
FT /note="Missing (in isoform Ankyrin-iPLA2-1)"
FT /evidence="ECO:0000303|PubMed:9417066"
FT /id="VSP_000282"
FT VAR_SEQ 500..806
FT /note="Missing (in isoform Ankyrin-iPLA2-2)"
FT /evidence="ECO:0000303|PubMed:9417066"
FT /id="VSP_000280"
FT VARIANT 58
FT /note="V -> I (in dbSNP:rs11570605)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_018961"
FT VARIANT 63
FT /note="R -> G (in dbSNP:rs11570606)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_018962"
FT VARIANT 70
FT /note="R -> Q (in dbSNP:rs11570607)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_018963"
FT VARIANT 183
FT /note="D -> N (in dbSNP:rs11570646)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_018964"
FT VARIANT 310
FT /note="V -> E (in NBIA2A; dbSNP:rs121908682)"
FT /evidence="ECO:0000269|PubMed:16783378"
FT /id="VAR_029371"
FT VARIANT 341
FT /note="A -> T (in NBIA2A; complete loss of phospholipase
FT and lysophospholipase activities)"
FT /evidence="ECO:0000269|PubMed:16783378,
FT ECO:0000269|PubMed:20886109"
FT /id="VAR_083527"
FT VARIANT 343
FT /note="A -> T (in dbSNP:rs11570680)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_018965"
FT VARIANT 484
FT /note="D -> G (in NBIA2A)"
FT /evidence="ECO:0000269|PubMed:23749988"
FT /id="VAR_070600"
FT VARIANT 517
FT /note="G -> C (in NBIA2A; complete loss of phospholipase
FT and lysophospholipase activities)"
FT /evidence="ECO:0000269|PubMed:16783378,
FT ECO:0000269|PubMed:20886109"
FT /id="VAR_083528"
FT VARIANT 545
FT /note="K -> T (in NBIA2B; dbSNP:rs121908681)"
FT /evidence="ECO:0000269|PubMed:16783378"
FT /id="VAR_029372"
FT VARIANT 550
FT /note="R -> W (in dbSNP:rs1004616610)"
FT /evidence="ECO:0000269|PubMed:28887846"
FT /id="VAR_079753"
FT VARIANT 632
FT /note="R -> W (in NBIA2B; increases phospholipase,
FT lysophospholipase and thioesterase activities;
FT dbSNP:rs121908683)"
FT /evidence="ECO:0000269|PubMed:16783378,
FT ECO:0000269|PubMed:20886109"
FT /id="VAR_029373"
FT VARIANT 638
FT /note="G -> R (in NBIA2A; complete loss of phospholipase
FT and lysophospholipase activities)"
FT /evidence="ECO:0000269|PubMed:16783378,
FT ECO:0000269|PubMed:20886109"
FT /id="VAR_083529"
FT VARIANT 661
FT /note="T -> M (in NBIA2A; dbSNP:rs767689496)"
FT /evidence="ECO:0000269|PubMed:23749988"
FT /id="VAR_070601"
FT VARIANT 691
FT /note="Missing (in NBIA2A and NBIA2B; significantly reduces
FT phospholipase and lysophospholipase activities)"
FT /evidence="ECO:0000269|PubMed:16783378,
FT ECO:0000269|PubMed:17033970, ECO:0000269|PubMed:20886109"
FT /id="VAR_029374"
FT VARIANT 741
FT /note="R -> Q (in PARK14; has no effect on phospholipase,
FT lysophospholipase and thioesterase activities;
FT dbSNP:rs121908686)"
FT /evidence="ECO:0000269|PubMed:18570303,
FT ECO:0000269|PubMed:20886109"
FT /id="VAR_062530"
FT VARIANT 741
FT /note="R -> W (in NBIA2A; significantly reduces
FT phospholipase and lysophospholipase activities)"
FT /evidence="ECO:0000269|PubMed:16783378,
FT ECO:0000269|PubMed:20886109"
FT /id="VAR_083530"
FT VARIANT 747
FT /note="R -> W (in PARK14; has no effect on phospholipase,
FT lysophospholipase and thioesterase activities;
FT dbSNP:rs121908687)"
FT /evidence="ECO:0000269|PubMed:18570303,
FT ECO:0000269|PubMed:20886109"
FT /id="VAR_062531"
FT VARIANT 774
FT /note="S -> T (in dbSNP:rs34184838)"
FT /id="VAR_037903"
FT VARIANT 790..806
FT /note="Missing (in NBIA2A; nonsense substitution producing
FT a stop codon; complete loss of phospholipase and
FT lysophospholipase activities)"
FT /evidence="ECO:0000269|PubMed:16783378,
FT ECO:0000269|PubMed:20886109"
FT /id="VAR_083531"
FT MUTAGEN 519
FT /note="S->A: Abolishes phospholipase and lysophospholipase
FT activities."
FT /evidence="ECO:0000269|PubMed:20886109"
FT CONFLICT 11
FT /note="F -> S (in Ref. 3; AAD30424)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="N -> D (in Ref. 2; AAD41722/AAD41723)"
FT /evidence="ECO:0000305"
FT CONFLICT 579
FT /note="K -> I (in Ref. 3; AAD30424)"
FT /evidence="ECO:0000305"
FT CONFLICT 686
FT /note="K -> I (in Ref. 3; AAD30424)"
FT /evidence="ECO:0000305"
FT CONFLICT 801
FT /note="Q -> H (in Ref. 1; AAC97486)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 806 AA; 89903 MW; 8E55CD4EB9ACAD8B CRC64;
MQFFGRLVNT FSGVTNLFSN PFRVKEVAVA DYTSSDRVRE EGQLILFQNT PNRTWDCVLV
NPRNSQSGFR LFQLELEADA LVNFHQYSSQ LLPFYESSPQ VLHTEVLQHL TDLIRNHPSW
SVAHLAVELG IRECFHHSRI ISCANCAENE EGCTPLHLAC RKGDGEILVE LVQYCHTQMD
VTDYKGETVF HYAVQGDNSQ VLQLLGRNAV AGLNQVNNQG LTPLHLACQL GKQEMVRVLL
LCNARCNIMG PNGYPIHSAM KFSQKGCAEM IISMDSSQIH SKDPRYGASP LHWAKNAEMA
RMLLKRGCNV NSTSSAGNTA LHVAVMRNRF DCAIVLLTHG ANADARGEHG NTPLHLAMSK
DNVEMIKALI VFGAEVDTPN DFGETPTFLA SKIGRLVTRK AILTLLRTVG AEYCFPPIHG
VPAEQGSAAP HHPFSLERAQ PPPISLNNLE LQDLMHISRA RKPAFILGSM RDEKRTHDHL
LCLDGGGVKG LIIIQLLIAI EKASGVATKD LFDWVAGTST GGILALAILH SKSMAYMRGM
YFRMKDEVFR GSRPYESGPL EEFLKREFGE HTKMTDVRKP KVMLTGTLSD RQPAELHLFR
NYDAPETVRE PRFNQNVNLR PPAQPSDQLV WRAARSSGAA PTYFRPNGRF LDGGLLANNP
TLDAMTEIHE YNQDLIRKGQ ANKVKKLSIV VSLGTGRSPQ VPVTCVDVFR PSNPWELAKT
VFGAKELGKM VVDCCTDPDG RAVDRARAWC EMVGIQYFRL NPQLGTDIML DEVSDTVLVN
ALWETEVYIY EHREEFQKLI QLLLSP
