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Details on Person UniProt:O60733 PLA2G6

Class:IdReferenceGeneProduct:61216
_chainChangeLogchain:1-806 added on Fri February 6 2015
_displayNameUniProt:O60733 PLA2G6
_timestamp2025-02-21 19:52:23
chainchain:1-806
checksum8E55CD4EB9ACAD8B
commentFUNCTION 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.
descriptionrecommendedName: 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
geneNamePLA2G6
PLPLA9
identifierO60733
isSequenceChangedFALSE
keywordAlternative 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
namePLA2G6
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8989733] ENSEMBL:ENSG00000184381 PLA2G6 [Homo sapiens]
secondaryIdentifierPLPL9_HUMAN
A8K597
B0QYE8
O75645
Q8N452
Q9UG29
Q9UIT0
Q9Y671
sequenceLength806
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:151674] UniProt:O60733-2 PLA2G6 [Homo sapiens]
[ReferenceIsoform:151675] UniProt:O60733-3 PLA2G6 [Homo sapiens]
[ReferenceIsoform:151676] UniProt:O60733-4 PLA2G6 [Homo sapiens]
[ReferenceIsoform:401723] UniProt:O60733-1 PLA2G6 [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:201596] PLA2G6 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:1524076] PLA2G6 [mitochondrial inner membrane] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:O60733 PLA2G6 (61216)
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