| IED ID | IndEnz0010001747 |
| Enzyme Type ID | esterase001747 |
| Protein Name |
85/88 kDa calcium-independent phospholipase A2 CaI-PLA2 EC 3.1.1.4 2-lysophosphatidylcholine acylhydrolase EC 3.1.1.5 Group VI phospholipase A2 GVI PLA2 Intracellular membrane-associated calcium-independent phospholipase A2 beta iPLA2-beta Palmitoyl-CoA hydrolase EC 3.1.2.2 Patatin-like phospholipase domain-containing protein 9 PNPLA9 |
| Gene Name | Pla2g6 Pnpla9 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MQFFGRLVNTLSSVTNLFSNPFRVKEVSLTDYVSSERVREEGQLILLQNVSNRTWDCVLVSPRNPQSGFRLFQLESEADALVNFQQFSSQLPPFYESSVQVLHVEVLQHLTDLIRNHPSWTVTHLAVELGIRECFHHSRIISCANSTENEEGCTPLHLACRKGDSEILVELVQYCHAQMDVTDNKGETAFHYAVQGDNPQVLQLLGKNASAGLNQVNNQGLTPLHLACKMGKQEMVRVLLLCNARCNIMGPGGFPIHTAMKFSQKGCAEMIISMDSNQIHSKDPRYGASPLHWAKNAEMARMLLKRGCDVDSTSSSGNTALHVAVMRNRFDCVMVLLTYGANAGARGEHGNTPLHLAMSKDNMEMVKALIVFGAEVDTPNDFGETPALIASKISKLITRKALLTLLKTVGADHHFPIIQGVSTEQGSAAATHPLFSLDRTQPPAISLNNLELQDLMPISRARKPAFILSSMRDEKRSHDHLLCLDGGGVKGLVIIQLLIAIEKASGVATKDLFDWVAGTSTGGILALAILHSKSMAYMRGVYFRMKDEVFRGSRPYESGPLEEFLKREFGEHTKMTDVKKPKVMLTGTLSDRQPAELHLFRNYDAPEAVREPRCNQNINLKPPTQPADQLVWRAARSSGAAPTYFRPNGRFLDGGLLANNPTLDAMTEIHEYNQDMIRKGQGNKVKKLSIVVSLGTGKSPQVPVTCVDVFRPSNPWELAKTVFGAKELGKMVVDCCTDPDGRAVDRARAWCEMVGIQYFRLNPQLGSDIMLDEVSDAVLVNALWETEVYIYEHREEFQKLVQLLLSP |
| Enzyme Length | 807 |
| Uniprot Accession Number | P97819 |
| Absorption | |
| Active Site | ACT_SITE 520; /note=Nucleophile; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161; ACT_SITE 653; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by calcium-activated calmodulin (By similarity). Activated by ATP (PubMed:18937505, PubMed:17895289). Inhibited by bromoenol lactone (BEL) (PubMed:18937505, PubMed:17895289). {ECO:0000250|UniProtKB:P97570, ECO:0000269|PubMed:17895289, ECO:0000269|PubMed:18937505}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4; Evidence={ECO:0000269|PubMed:18937505};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802; Evidence={ECO:0000305|PubMed:18937505}; CATALYTIC ACTIVITY: Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) + hexadecanoate; Xref=Rhea:RHEA:41223, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:72998, ChEBI:CHEBI:72999; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41224; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:38779, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:72998, ChEBI:CHEBI:73001; Evidence={ECO:0000250|UniProtKB:O60733};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38780; Evidence={ECO:0000250|UniProtKB:O60733}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:40811, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30245, ChEBI:CHEBI:72998, ChEBI:CHEBI:73002; Evidence={ECO:0000269|PubMed:18937505};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812; Evidence={ECO:0000305|PubMed:18937505}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:40427, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395, ChEBI:CHEBI:72998, ChEBI:CHEBI:73003; Evidence={ECO:0000250|UniProtKB:O60733};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40428; Evidence={ECO:0000250|UniProtKB:O60733}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-octadecanoyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:40519, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395, ChEBI:CHEBI:73858, ChEBI:CHEBI:74965; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40520; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + H(+); Xref=Rhea:RHEA:40431, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395, ChEBI:CHEBI:73004, ChEBI:CHEBI:73009; Evidence={ECO:0000269|PubMed:17895289};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40432; Evidence={ECO:0000305|PubMed:17895289}; CATALYTIC ACTIVITY: Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1-hexadecanoyl-sn-glycero-3-phosphate + H(+) + hexadecanoate; Xref=Rhea:RHEA:63304, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57518, ChEBI:CHEBI:72859; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63305; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8}; CATALYTIC ACTIVITY: Reaction=a 1-acyl-sn-glycero-3-phosphocholine + H2O = a fatty acid + H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:15177, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:28868, ChEBI:CHEBI:58168; EC=3.1.1.5; Evidence={ECO:0000250|UniProtKB:O60733};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15178; Evidence={ECO:0000250|UniProtKB:O60733}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) + hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40435, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:72998; Evidence={ECO:0000250|UniProtKB:O60733};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436; Evidence={ECO:0000250|UniProtKB:O60733}; CATALYTIC ACTIVITY: Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40831, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:32395, ChEBI:CHEBI:74344; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40832; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40827, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:32395, ChEBI:CHEBI:76079; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40828; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8}; CATALYTIC ACTIVITY: Reaction=1-O-hexadecyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-O-hexadecyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:41067, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395, ChEBI:CHEBI:55430, ChEBI:CHEBI:64496; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41068; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8}; CATALYTIC ACTIVITY: Reaction=1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:40479, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:44811, ChEBI:CHEBI:64496; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40480; Evidence={ECO:0000250|UniProtKB:A0A3L7I2I8}; CATALYTIC ACTIVITY: Reaction=H2O + hexadecanoyl-CoA = CoA + H(+) + hexadecanoate; Xref=Rhea:RHEA:16645, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379; EC=3.1.2.2; Evidence={ECO:0000269|PubMed:18937505};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16646; Evidence={ECO:0000305|PubMed:18937505}; CATALYTIC ACTIVITY: Reaction=1',3'-bis[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H2O = (9Z)-octadecenoate + 1'-[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-3'-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H(+); Xref=Rhea:RHEA:40463, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:77253, ChEBI:CHEBI:77259; Evidence={ECO:0000250|UniProtKB:O60733};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40464; Evidence={ECO:0000250|UniProtKB:O60733}; CATALYTIC ACTIVITY: Reaction=1'-[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-3'-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H2O = (9Z)-octadecenoate + 1',3'-bis-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H(+); Xref=Rhea:RHEA:40467, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:77256, ChEBI:CHEBI:77259; Evidence={ECO:0000250|UniProtKB:O60733};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40468; Evidence={ECO:0000250|UniProtKB:O60733}; CATALYTIC ACTIVITY: Reaction=1',3'-bis-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + H2O = (9Z,12Z)-octadecadienoate + 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + H(+); Xref=Rhea:RHEA:52812, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30245, ChEBI:CHEBI:83580, ChEBI:CHEBI:83581; Evidence={ECO:0000269|PubMed:24648512};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:52814; Evidence={ECO:0000305|PubMed:24648512}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoethanolamine + 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + H(+); Xref=Rhea:RHEA:63256, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:75036, ChEBI:CHEBI:78832, ChEBI:CHEBI:146277; Evidence={ECO:0000250|UniProtKB:P97570};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63257; Evidence={ECO:0000250|UniProtKB:P97570}; |
| DNA Binding | |
| EC Number | 3.1.1.4; 3.1.1.5; 3.1.2.2 |
| Enzyme Function | FUNCTION: Calcium-independent phospholipase involved in phospholipid remodeling with implications in cellular membrane homeostasis, mitochondrial integrity and signal transduction. Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 or sn-2 position of phospholipids (phospholipase A1 and A2 activity respectively), producing lysophospholipids that are used in deacylation-reacylation cycles (PubMed:18937505). Hydrolyzes both saturated and unsaturated long fatty acyl chains in various glycerophospholipid classes such as phosphatidylcholines, phosphatidylethanolamines and phosphatidates, with a preference for hydrolysis at sn-2 position. Can further hydrolyze lysophospholipids carrying saturated fatty acyl chains (lysophospholipase activity). Upon oxidative stress, contributes to remodeling of mitochondrial phospholipids in pancreatic beta cells, in a repair mechanism to reduce oxidized lipid content (By similarity). Preferentially hydrolyzes oxidized polyunsaturated fatty acyl chains from cardiolipins, yielding monolysocardiolipins that can be reacylated with unoxidized fatty acyls to regenerate native cardiolipin species. Hydrolyzes oxidized glycerophosphoethanolamines present in pancreatic islets, releasing oxidized polyunsaturated fatty acids such as hydroxyeicosatetraenoates (HETEs) (PubMed:24648512). Has thioesterase activity toward fatty-acyl CoA releasing CoA-SH known to facilitate fatty acid transport and beta-oxidation in mitochondria particularly in skeletal muscle (PubMed:18937505). Plays a role in regulation of membrane dynamics and homeostasis. Selectively hydrolyzes sn-2 arachidonoyl group in plasmalogen phospholipids, structural components of lipid rafts and myelin (By similarity). Regulates F-actin polymerization at the pseudopods, which is required for both speed and directionality of MCP1/CCL2-induced monocyte chemotaxis (By similarity). Targets membrane phospholipids to produce potent lipid signaling messengers. Generates lysophosphatidate (LPA, 1-acyl-glycerol-3-phosphate), which acts via G-protein receptors in various cell types. Has phospholipase A2 activity toward platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), likely playing a role in inactivation of this potent pro-inflammatory signaling lipid (By similarity). In response to glucose, amplifies calcium influx in pancreatic beta cells to promote INS secretion (PubMed:17895289). {ECO:0000250|UniProtKB:A0A3L7I2I8, ECO:0000250|UniProtKB:O60733, ECO:0000269|PubMed:17895289, ECO:0000269|PubMed:18937505, ECO:0000269|PubMed:24648512}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Chain (1); Domain (1); Modified residue (1); Motif (3); Region (2); Repeat (9); Transmembrane (2) |
| Keywords | ANK repeat;Alternative splicing;Calmodulin-binding;Cell membrane;Cell projection;Chemotaxis;Cytoplasm;Direct protein sequencing;Hydrolase;Lipid metabolism;Membrane;Mitochondrion;Phospholipid metabolism;Phosphoprotein;Reference proteome;Repeat;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11563837}. Cell membrane {ECO:0000269|PubMed:11563837}. Mitochondrion {ECO:0000269|PubMed:24648512}. Cell projection, pseudopodium {ECO:0000250|UniProtKB:O60733}. Note=Recruited to the membrane-enriched pseudopods upon MCP1/CCL2 stimulation in monocytes. {ECO:0000250|UniProtKB:O60733}. |
| Modified Residue | MOD_RES 13; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P97570 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 12167650; 14610273; 14681479; 15024020; 15252026; 15946940; 16141072; 16732058; 16818490; 16926189; 17613534; 17627946; 17873277; 18156193; 18202189; 18208975; 18349124; 18799693; 18927078; 18952717; 19261908; 19893029; 19914213; 19917703; 20032468; 20059953; 20382858; 20463052; 20521843; 20530749; 20686114; 20732873; 21191104; 21228317; 21267068; 21880721; 21984569; 22046428; 22094335; 22194610; 22218592; 22349267; 22363752; 22389508; 22442204; 22637477; 22680611; 22778252; 23124680; 24337743; 24482376; 24791136; 24858037; 24919816; 25004092; 25213337; 25329652; 25337551; 25562715; 25762722; 25957555; 26182903; 26206229; 26655718; 26755131; 26828067; 26857573; 26873633; 27078024; 27226532; 27395788; 27650501; 27655917; 27789386; 28655161; 2888882; 28888832; 30088174; 30735854; 30735855; 31337982; 31409057; 32818532; 32957701; 33080873; 33087576; 33177235; 33441441; 34131139; 34207793; 34520727; 9361012; |
| Motif | MOTIF 486..491; /note=GXGXXG; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161; MOTIF 518..522; /note=GXSXG; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161; MOTIF 653..655; /note=DGA/G; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161 |
| Gene Encoded By | |
| Mass | 89,560 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:15801; RHEA:15802; RHEA:41223; RHEA:41224; RHEA:38779; RHEA:38780; RHEA:40811; RHEA:40812; RHEA:40427; RHEA:40428; RHEA:40519; RHEA:40520; RHEA:40431; RHEA:40432; RHEA:63304; RHEA:63305; RHEA:15177; RHEA:15178; RHEA:40435; RHEA:40436; RHEA:40831; RHEA:40832; RHEA:40827; RHEA:40828; RHEA:41067; RHEA:41068; RHEA:40479; RHEA:40480; RHEA:16645; RHEA:16646; RHEA:40463; RHEA:40464; RHEA:40467; RHEA:40468; RHEA:52812; RHEA:52814; RHEA:63256; RHEA:63257 |
| Cross Reference Brenda |