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cytosolic phospholipase A2; phospholipase A2 group IVA; includes: phospholipase A2; phosphatidylcholine 2-acylhydrolase; lysophospholipase (PLA2G4A, PLA2G4)
Function:
- selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid
- together with its lysophospholipid activity, implicated in initiation of the inflammatory response
- stimulated by agonists such as ATP, EGF, thrombin & bradykinin as well as by cytosolic Ca+2
- activated by phosphorylation at both Ser-505 & Ser-727
- interacts with KAT5
phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate
2-lysophosphatidylcholine + H2O = glycerophosphocholine + a carboxylate
Kinetic parameters:
- Vmax=2.7 umol/min/mg enzyme for the phospholipase A2 reaction
- Vmax=4.6 umol/min/mg enzyme for the lysophosphatase reaction
Structure:
- the N-terminal C2 domain
- associates with lipid membranes upon Ca+2 binding
- modulates enzyme activity by presenting the active site to its substrate in response to increases in cytosolic Ca+2
- contains 1 C2 domain
- contains 1 PLA2c domain
Compartment:
- cytoplasm, cytoplasmic vesicle
- translocation from cytoplasm to membrane vesicles (Ca+2-dependent)
Expression:
- expressed in macrophages, platelets, neutrophils, fibroblasts & lung endothelium
General
lysophospholipase
phospholipase-A2 [PLA2] type 4; cytoplasmic phospholipase A2 (cPLA2)
Properties
SIZE: entity length = 749 aa
MW = 85 kD
COMPARTMENT: cytoplasm
MOTIF: Phospholipid binding {1-178}
MOTIF: C2 domain {5-106}
MOTIF: binding site
FOR-BINDING-OF: phospholipid
Ca+2-binding site
Ca+2-binding site
SITE: 40-40
Ca+2-binding site
SITE: 41-41
Ca+2-binding site
SITE: 43-43
Ca+2-binding site
SITE: 65-65
Ca+2-binding site
SITE: 93-93
Ca+2-binding site
SITE: 94-94
Ca+2-binding site
SITE: 95-95
PLA2c {140-740}
MOTIF: serine residue {S228}
Thr phosphorylation site {T268}
Ser phosphorylation site {S434}
Ser phosphorylation site {S435}
Ser phosphorylation site {S437}
Ser phosphorylation site {S505}
Tyr phosphorylation site {Y535}
aspartate residue {D549}
Ser phosphorylation site {S727}
Ser phosphorylation site {S729}
Database Correlations
OMIM 600522
MORBIDMAP 600522
UniProt P47712
PFAM correlations
Entrez Gene 5321
KEGG correlations
ENZYME correlations
References
- UniProt :accession P47712
- NIEHS-SNPs
http://egp.gs.washington.edu/data/pla2g4a/