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Details on Person UniProt:O60733-4 PLA2G6
| Class:Id | ReferenceIsoform:151676 |
|---|---|
| _chainChangeLog | chain:1-806 added on Fri February 6 2015 |
| _displayName | UniProt:O60733-4 PLA2G6 |
| _timestamp | 2025-02-21 19:52:23 |
| chain | chain:1-806 |
| checksum | 8E55CD4EB9ACAD8B |
| comment | 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:10092647, PubMed:10336645, PubMed:20886109, PubMed:9417066). 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 (PubMed:10092647, PubMed:10336645, PubMed:20886109). Can further hydrolyze lysophospholipids carrying saturated fatty acyl chains (lysophospholipase activity) (PubMed:20886109). Upon oxidative stress, contributes to remodeling of mitochondrial phospholipids in pancreatic beta cells, in a repair mechanism to reduce oxidized lipid content (PubMed:23533611). Preferentially hydrolyzes oxidized polyunsaturated fatty acyl chains from cardiolipins, yielding monolysocardiolipins that can be reacylated with unoxidized fatty acyls to regenerate native cardiolipin species (By similarity). Hydrolyzes oxidized glycerophosphoethanolamines present in pancreatic islets, releasing oxidized polyunsaturated fatty acids such as hydroxyeicosatetraenoates (HETEs) (By similarity). 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:20886109). 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 (PubMed:18208975). 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 (By similarity). 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 (By similarity).FUNCTION Lacks the catalytic domain and may act as a negative regulator of the catalytically active isoforms.FUNCTION Lacks the catalytic domain and may act as a negative regulator of the catalytically active isoforms.CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+)CATALYTIC ACTIVITY a 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl-sn-glycero-3-phosphocholine + a fatty acid + H(+)CATALYTIC ACTIVITY 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+)CATALYTIC ACTIVITY 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + (9Z)-octadecenoate + H(+)CATALYTIC ACTIVITY 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+)CATALYTIC ACTIVITY 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)CATALYTIC ACTIVITY 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 1-octadecanoyl-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)CATALYTIC ACTIVITY 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)CATALYTIC ACTIVITY 1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1-hexadecanoyl-sn-glycero-3-phosphate + hexadecanoate + H(+)CATALYTIC ACTIVITY a 1-acyl-sn-glycero-3-phosphocholine + H2O = sn-glycerol 3-phosphocholine + a fatty acid + H(+)CATALYTIC ACTIVITY 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = sn-glycerol 3-phosphocholine + hexadecanoate + H(+)CATALYTIC ACTIVITY 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = sn-glycerol 3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)CATALYTIC ACTIVITY 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + H2O = sn-glycerol 3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)CATALYTIC ACTIVITY 1-O-hexadecyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)CATALYTIC ACTIVITY 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H(+)CATALYTIC ACTIVITY hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+)CATALYTIC ACTIVITY 1',3'-bis[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H2O = 1'-[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-3'-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + (9Z)-octadecenoate + H(+)CATALYTIC ACTIVITY 1'-[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-3'-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H2O = 1',3'-bis-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + (9Z)-octadecenoate + H(+)CATALYTIC ACTIVITY 1',3'-bis-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + H2O = 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + (9Z,12Z)-octadecadienoate + H(+)CATALYTIC ACTIVITY 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(+)ACTIVITY REGULATION Activated by ATP (PubMed:10092647). Inhibited by calcium-activated calmodulin (By similarity). Inhibited by bromoenol lactone (BEL) (By similarity).SUBUNIT Homodimer formed by catalytic domains tightly interacting through a large hydrophobic interface. The contact area involves 3 alpha helices, several loops and a part of the beta sheet from each monomer. Both active sites of the dimer are in close proximity adopting an open conformation that provide sufficient space for phospholipid access and favoring cooperativity in deacylation-reacylation reactions. Each monomer has 9 ankyrin repeats stacked side-by-side in an elongated structure oriented outwards from the catalytic core.INTERACTION Recruited to the membrane-enriched pseudopods upon MCP1/CCL2 stimulation in monocytes.ALTERNATIVE PRODUCTS Four different transcripts were found to be expressed in a distinct tissue distribution.DOMAIN Has two putative calmodulin binding domains, the 1-9-14 and IQ motifs. One calmodulin molecule interacts with PLA2G6 dimer, likely through 1-9-14 motif on each monomer (By similarity). Binds calmodulin in a calcium-dependent way (By similarity).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.PHARMACEUTICAL Potential target for therapeutic intervention of Barth syndrome. |
| description | recommendedName: 85/88 kDa calcium-independent phospholipase A2 shortName: CaI-PLA2 ecNumber evidence="12"3.1.1.4 alternativeName: 2-lysophosphatidylcholine acylhydrolase ecNumber evidence="12"3.1.1.5 alternativeName: Group VI phospholipase A2 shortName: GVI PLA2 alternativeName: Intracellular membrane-associated calcium-independent phospholipase A2 beta shortName: iPLA2-beta alternativeName: Palmitoyl-CoA hydrolase ecNumber evidence="12"3.1.2.2 alternativeName: Patatin-like phospholipase domain-containing protein 9 shortName: PNPLA9 |
| geneName | PLA2G6 PLPLA9 |
| identifier | O60733 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | Alternative splicing ANK repeat Calmodulin-binding Cell membrane Cell projection Chemotaxis Cytoplasm Disease variant Dystonia Hydrolase Lipid metabolism Membrane Mitochondrion Neurodegeneration Parkinson disease Parkinsonism Pharmaceutical Phospholipid metabolism Proteomics identification Reference proteome Repeat Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | PLA2G6 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8989733] ENSEMBL:ENSG00000184381 PLA2G6 [Homo sapiens] |
| secondaryIdentifier | PLPL9_HUMAN A8K597 B0QYE8 O75645 Q8N452 Q9UG29 Q9UIT0 Q9Y671 |
| sequenceLength | 806 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | O60733-4 |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:O60733-4 PLA2G6 (151676)
