PLPL8_MOUSE
ID PLPL8_MOUSE Reviewed; 776 AA.
AC Q8K1N1; Q3TH33; Q8VEC0; Q9DC20;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Calcium-independent phospholipase A2-gamma {ECO:0000305|PubMed:17923475};
DE EC=3.1.1.- {ECO:0000269|PubMed:17923475, ECO:0000269|PubMed:28442572};
DE EC=3.1.1.5 {ECO:0000250|UniProtKB:Q9NP80};
DE AltName: Full=Intracellular membrane-associated calcium-independent phospholipase A2 gamma;
DE Short=iPLA2-gamma {ECO:0000303|PubMed:17923475};
DE AltName: Full=Patatin-like phospholipase domain-containing protein 8;
GN Name=Pnpla8 {ECO:0000312|MGI:MGI:1914702}; Synonyms=Ipla22, Ipla2g;
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].
RX PubMed=10833412; DOI=10.1006/bbrc.2000.2776;
RA Tanaka H., Takeya R., Sumimoto H.;
RT "A novel intracellular membrane-bound calcium-independent phospholipase
RT A(2).";
RL Biochem. Biophys. Res. Commun. 272:320-326(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Egg, Kidney, and Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; 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 [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17213206; DOI=10.1074/jbc.m607307200;
RA Mancuso D.J., Han X., Jenkins C.M., Lehman J.J., Sambandam N., Sims H.F.,
RA Yang J., Yan W., Yang K., Green K., Abendschein D.R., Saffitz J.E.,
RA Gross R.W.;
RT "Dramatic accumulation of triglycerides and precipitation of cardiac
RT hemodynamic dysfunction during brief caloric restriction in transgenic
RT myocardium expressing human calcium-independent phospholipase A2gamma.";
RL J. Biol. Chem. 282:9216-9227(2007).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DISRUPTION PHENOTYPE, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17923475; DOI=10.1074/jbc.m707795200;
RA Mancuso D.J., Sims H.F., Han X., Jenkins C.M., Guan S.P., Yang K.,
RA Moon S.H., Pietka T., Abumrad N.A., Schlesinger P.H., Gross R.W.;
RT "Genetic ablation of calcium-independent phospholipase A2gamma leads to
RT alterations in mitochondrial lipid metabolism and function resulting in a
RT deficient mitochondrial bioenergetic phenotype.";
RL J. Biol. Chem. 282:34611-34622(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-730, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=28442572; DOI=10.1074/jbc.m117.783068;
RA Liu G.Y., Moon S.H., Jenkins C.M., Li M., Sims H.F., Guan S., Gross R.W.;
RT "The phospholipase iPLA2gamma is a major mediator releasing oxidized
RT aliphatic chains from cardiolipin, integrating mitochondrial bioenergetics
RT and signaling.";
RL J. Biol. Chem. 292:10672-10684(2017).
CC -!- FUNCTION: Calcium-independent and membrane-bound phospholipase, that
CC catalyzes the esterolytic cleavage of fatty acids from
CC glycerophospholipids to yield free fatty acids and lysophospholipids,
CC hence regulating membrane physical properties and the release of lipid
CC second messengers and growth factors (PubMed:17923475,
CC PubMed:28442572). Hydrolyzes phosphatidylethanolamine,
CC phosphatidylcholine and probably phosphatidylinositol with a possible
CC preference for the former. Has also a broad substrate specificity in
CC terms of fatty acid moieties, hydrolyzing saturated and mono-
CC unsaturated fatty acids at nearly equal rates from either the sn-1 or
CC sn-2 position in diacyl phosphatidylcholine. However, has a weak
CC activity toward polyunsaturated fatty acids at the sn-2 position, and
CC thereby favors the production of 2-arachidonoyl
CC lysophosphatidylcholine, a key branch point metabolite in eicosanoid
CC signaling. On the other hand, can produce arachidonic acid from the sn-
CC 1 position of diacyl phospholipid and from the sn-2 position of
CC arachidonate-containing plasmalogen substrates. Therefore, plays an
CC important role in the mobilization of arachidonic acid in response to
CC cellular stimuli and the generation of lipid second messengers. Can
CC also hydrolyze lysophosphatidylcholine (By similarity). In the
CC mitochondrial compartment, catalyzes the hydrolysis and release of
CC oxidized aliphatic chains from cardiolipin and integrates mitochondrial
CC bioenergetics and signaling. It is essential for maintaining efficient
CC bioenergetic mitochondrial function through tailoring mitochondrial
CC membrane lipid metabolism and composition (PubMed:17923475,
CC PubMed:28442572). {ECO:0000250|UniProtKB:Q9NP80,
CC ECO:0000269|PubMed:17923475, ECO:0000269|PubMed:28442572}.
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;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:18689,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:57875;
CC Evidence={ECO:0000269|PubMed:17923475};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18690;
CC Evidence={ECO:0000269|PubMed:17923475};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + H2O = a 1-
CC acyl-sn-glycero-3-phosphoethanolamine + a fatty acid + H(+);
CC Xref=Rhea:RHEA:44604, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28868, ChEBI:CHEBI:64381, ChEBI:CHEBI:64612;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44605;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-(1Z-alkenyl)-2-acyl-sn-glycero-3-phosphocholine + H2O = 1-
CC O-(1Z-alkenyl)-sn-glycero-3-phosphocholine + a fatty acid + H(+);
CC Xref=Rhea:RHEA:44068, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28868, ChEBI:CHEBI:77286, ChEBI:CHEBI:77287;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44069;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
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:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15178;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphocholine + H2O = 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-
CC glycero-3-phosphocholine + H(+) + hexadecanoate;
CC Xref=Rhea:RHEA:40571, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:73003, ChEBI:CHEBI:76079;
CC Evidence={ECO:0000269|PubMed:17923475};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40572;
CC Evidence={ECO:0000269|PubMed:17923475};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-acyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphocholine
CC + H2O = (9Z,12Z)-octadecadienoate + a 1-acyl-sn-glycero-3-
CC phosphocholine + H(+); Xref=Rhea:RHEA:40643, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30245, ChEBI:CHEBI:58168,
CC ChEBI:CHEBI:60000; Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40644;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-acyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-
CC phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + a 1-acyl-
CC sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:40651,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:58168, ChEBI:CHEBI:75063;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40652;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
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:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40428;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine
CC + H2O = (9Z)-octadecenoate + 1-octadecanoyl-sn-glycero-3-
CC phosphocholine + H(+); Xref=Rhea:RHEA:40819, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:73858,
CC ChEBI:CHEBI:75034; Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40820;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine
CC + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-
CC phosphocholine + H(+); Xref=Rhea:RHEA:38779, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:72998,
CC ChEBI:CHEBI:73001; Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38780;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
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:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-acyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-
CC phosphoethanolamine + H2O = (9Z,12Z)-octadecadienoate + a 1-acyl-sn-
CC glycero-3-phosphoethanolamine + H(+); Xref=Rhea:RHEA:40639,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30245,
CC ChEBI:CHEBI:64381, ChEBI:CHEBI:75069;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40640;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-acyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-
CC phosphoethanolamine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + a 1-
CC acyl-sn-glycero-3-phosphoethanolamine + H(+); Xref=Rhea:RHEA:40647,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:64381, ChEBI:CHEBI:75067;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40648;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
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:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40432;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine
CC + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H(+) +
CC octadecanoate; Xref=Rhea:RHEA:40823, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:25629, ChEBI:CHEBI:75034,
CC ChEBI:CHEBI:76071; Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40824;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phosphocholine + H2O = 2-(4Z,7Z,10Z,13Z,16Z,19Z-
CC docosahexaenoyl)-sn-glycero-3-phosphocholine + H(+) + hexadecanoate;
CC Xref=Rhea:RHEA:41063, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:74963, ChEBI:CHEBI:76085;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41064;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-(1Z)-hexadecenyl-2 (5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-
CC glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate +
CC 1-(1Z-hexadecenyl)-sn-glycero-3-phosphocholine + H(+);
CC Xref=Rhea:RHEA:40579, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:73850, ChEBI:CHEBI:77292;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40580;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-(1Z-hexadecenyl)-2-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphocholine + H2O = (9Z)-octadecenoate + 1-(1Z-hexadecenyl)-sn-
CC glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:67156,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:73850, ChEBI:CHEBI:86232;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67157;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
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:Q9NP80};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC Evidence={ECO:0000250|UniProtKB:Q9NP80};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1',3'-bis-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phospho]-glycerol + H2O = (9Z,12Z)-octadecadienoate + 1'-[1,2-di-
CC (9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phospho]-glycerol + H(+);
CC Xref=Rhea:RHEA:52812, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:83580, ChEBI:CHEBI:83581;
CC Evidence={ECO:0000269|PubMed:28442572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52813;
CC Evidence={ECO:0000269|PubMed:28442572};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1'-[1-acyl-2-(9-hydroxy-(10E,12Z)-octadecadienoyl)-sn-glycero-
CC 3-phospho]-3'-[1,2-diacyl-sn-glycero-3-phospho]-glycerol + H2O = 1'-
CC [1,2-diacyl-sn-glycero-3-phospho],3'-[1-acyl-sn-glycero-3-phospho]-
CC glycerol + 9-hydroxy-(10E,12Z)-octadecadienoate + H(+);
CC Xref=Rhea:RHEA:67272, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:64743, ChEBI:CHEBI:133820, ChEBI:CHEBI:167908;
CC Evidence={ECO:0000269|PubMed:28442572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67273;
CC Evidence={ECO:0000269|PubMed:28442572};
CC -!- ACTIVITY REGULATION: Calcium-independent phospholipase.
CC {ECO:0000250|UniProtKB:Q9NP80}.
CC -!- PATHWAY: Phospholipid metabolism. {ECO:0000269|PubMed:17923475,
CC ECO:0000269|PubMed:28442572}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q5XTS1}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5XTS1}. Mitochondrion membrane
CC {ECO:0000269|PubMed:17213206, ECO:0000269|PubMed:17923475}; Single-pass
CC membrane protein {ECO:0000305}. Peroxisome membrane
CC {ECO:0000269|PubMed:17213206}; Single-pass membrane protein
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in myocardium (at protein level).
CC {ECO:0000269|PubMed:17213206}.
CC -!- DISRUPTION PHENOTYPE: Mutants display multiple bioenergetic
CC dysfunctional phenotypes, including growth retardation, cold
CC intolerance, reduced exercise endurance, greatly increased mortality
CC from cardiac stress after transverse aortic constriction, abnormal
CC mitochondrial function with a 65% decrease in ascorbate-induced Complex
CC IV-mediated oxygen consumption, and a reduction in myocardial
CC cardiolipin content accompanied by an altered cardiolipin molecular
CC species composition. Myocardium of mutant mice contain more oxidized
CC cardiolipin (PubMed:28442572). {ECO:0000269|PubMed:17923475,
CC ECO:0000269|PubMed:28442572}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH19364.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB23417.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB044139; BAB97200.1; -; mRNA.
DR EMBL; AK004621; BAB23417.1; ALT_SEQ; mRNA.
DR EMBL; AK145776; BAE26645.1; -; mRNA.
DR EMBL; AK163211; BAE37236.1; -; mRNA.
DR EMBL; AK168475; BAE40365.1; -; mRNA.
DR EMBL; BC019364; AAH19364.1; ALT_INIT; mRNA.
DR EMBL; BC127056; AAI27057.1; -; mRNA.
DR CCDS; CCDS36436.1; -.
DR RefSeq; NP_080440.2; NM_026164.2.
DR AlphaFoldDB; Q8K1N1; -.
DR SMR; Q8K1N1; -.
DR BioGRID; 212196; 2.
DR STRING; 10090.ENSMUSP00000043286; -.
DR ChEMBL; CHEMBL3259504; -.
DR SwissLipids; SLP:000000594; -.
DR GlyGen; Q8K1N1; 2 sites.
DR iPTMnet; Q8K1N1; -.
DR PhosphoSitePlus; Q8K1N1; -.
DR SwissPalm; Q8K1N1; -.
DR EPD; Q8K1N1; -.
DR jPOST; Q8K1N1; -.
DR MaxQB; Q8K1N1; -.
DR PaxDb; Q8K1N1; -.
DR PeptideAtlas; Q8K1N1; -.
DR PRIDE; Q8K1N1; -.
DR ProteomicsDB; 289935; -.
DR Antibodypedia; 17333; 177 antibodies from 23 providers.
DR DNASU; 67452; -.
DR Ensembl; ENSMUST00000043082; ENSMUSP00000043286; ENSMUSG00000036257.
DR GeneID; 67452; -.
DR KEGG; mmu:67452; -.
DR UCSC; uc007nlp.1; mouse.
DR CTD; 50640; -.
DR MGI; MGI:1914702; Pnpla8.
DR VEuPathDB; HostDB:ENSMUSG00000036257; -.
DR eggNOG; KOG4231; Eukaryota.
DR GeneTree; ENSGT00940000154738; -.
DR InParanoid; Q8K1N1; -.
DR OMA; YKLWQAI; -.
DR OrthoDB; 1209603at2759; -.
DR PhylomeDB; Q8K1N1; -.
DR TreeFam; TF319230; -.
DR Reactome; R-MMU-1482788; Acyl chain remodelling of PC.
DR Reactome; R-MMU-1482839; Acyl chain remodelling of PE.
DR BioGRID-ORCS; 67452; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Pnpla8; mouse.
DR PRO; PR:Q8K1N1; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8K1N1; protein.
DR Bgee; ENSMUSG00000036257; Expressed in hindlimb stylopod muscle and 244 other tissues.
DR ExpressionAtlas; Q8K1N1; baseline and differential.
DR Genevisible; Q8K1N1; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; ISS:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0047499; F:calcium-independent phospholipase A2 activity; IMP:UniProtKB.
DR GO; GO:0004622; F:lysophospholipase activity; IEA:UniProtKB-EC.
DR GO; GO:0102545; F:phosphatidyl phospholipase B activity; IEA:UniProtKB-EC.
DR GO; GO:0008970; F:phospholipase A1 activity; IEA:RHEA.
DR GO; GO:0004620; F:phospholipase activity; IBA:GO_Central.
DR GO; GO:0019369; P:arachidonic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0050482; P:arachidonic acid secretion; ISO:MGI.
DR GO; GO:0032048; P:cardiolipin metabolic process; IMP:UniProtKB.
DR GO; GO:0008219; P:cell death; ISO:MGI.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; ISO:MGI.
DR GO; GO:0055088; P:lipid homeostasis; IMP:UniProtKB.
DR GO; GO:0034638; P:phosphatidylcholine catabolic process; ISO:MGI.
DR GO; GO:0046338; P:phosphatidylethanolamine catabolic process; ISO:MGI.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISO:MGI.
DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; IMP:UniProtKB.
DR CDD; cd07211; Pat_PNPLA8; 1.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR045217; PNPLA8-like.
DR InterPro; IPR002641; PNPLA_dom.
DR Pfam; PF01734; Patatin; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR PROSITE; PS51635; PNPLA; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Lipid degradation;
KW Lipid metabolism; Membrane; Mitochondrion; Peroxisome; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..776
FT /note="Calcium-independent phospholipase A2-gamma"
FT /id="PRO_0000303215"
FT TRANSMEM 469..489
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 439..634
FT /note="PNPLA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT REGION 216..276
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 306..334
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 443..448
FT /note="GXGXXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 475..479
FT /note="GXSXG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOTIF 621..623
FT /note="DGA/G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT COMPBIAS 218..243
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..334
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 477
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT ACT_SITE 621
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01161"
FT MOD_RES 730
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 438..441
FT /note="ILTI -> DAWV (in Ref. 3; AAH19364)"
FT /evidence="ECO:0000305"
FT CONFLICT 729
FT /note="M -> I (in Ref. 2; BAE40365)"
FT /evidence="ECO:0000305"
FT CONFLICT 749
FT /note="E -> Q (in Ref. 2; BAE40365)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 776 AA; 87381 MW; 1140CC8358B1E119 CRC64;
MSINLTLDIY IYFLNNARSL CGKQRSKQLH FVCSKQYWRM NHVNVHREFH TSKKSCKWNR
SEAHCSKHWH SPSNHGLHFG IVRLSTSAPK GLTKVSIHMS RIKSTLNSVS KAIFGSQNEM
VTRLAQFKPS SRILRKVSDK GWLKQKNVKQ AVESLKNYSD KSAGKNSLAE QKSYFADKEE
DSGKHSLFHY TYGITTRFGE SFSVLANHIN SYFKSKGKMS QTKEDKQLQD KPDLEERKSS
SPGPDTVADR PDSESPLEVK DKLSSPTQMP EAHPVSAKQS IANFLSRPTE GVQALVGGYI
GGLVPKLKSD PKSPPEEQEV SAKTEQAVNK DKKAEEKKRV LLQQEKIIAR VSIDNRTRAL
VQALRRTADP KLCITRVEEL TFHLLEFPEG KGVAIKEKII PYLLRLRQVK DETLQAAVRE
ILALIGYVDP VKGRGIRILT IDGGGTRGVV ALQTLRKLVE LTQKPIHQLF DYICGVSTGA
ILAFMLGLFH MPLDECEELY RKLGSDVFTQ NVIVGTVKMS WSHAFYDSNT WEKILKDRIG
SALMIETARN PACPKVAAIS TIVNRGQTPK AFVFRNYGHF PGTNSHYLGG CQYKMWQAIR
ASSAAPGYFA EYALGSDLHQ DGGLLLNNPS ALALHECKCI WPDTPLECIV SLGTGRYESD
VRNTSTYTSL KTKLSNVISS ATDTEEVHIM LDGLLPSDTY FRFNPVICEN IPLDESRDEK
LDQLQLEGMK YIERNDQKMK KVAKILSQEK TTLQKINDWI KLKSDMYEGL PFFSKL
