Detail Information for IndEnz0010001747
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