PLA2G4A phospho S505
Domain
The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic calcium (PubMed:11375391, PubMed:9430701, PubMed:9665851). In the presence of phosphoinositides, regulates phospholipase A2 and lysophospholipase activities in a calcium-independent way (PubMed:12672805).
Function
Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (PubMed:10358058, PubMed:14709560, PubMed:16617059, PubMed:17472963, PubMed:18451993, PubMed:27642067, PubMed:7794891, PubMed:8619991, PubMed:8702602, PubMed:9425121). Plays an important role in embryo implantation and parturition through its ability to trigger prostanoid production (By similarity). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:8619991, PubMed:9425121). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:9425121). In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids (PubMed:27642067). Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 position of phospholipids (phospholipase A1 activity) only if an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific (PubMed:7794891). Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides (PubMed:12672805). Has O-acyltransferase activity. Catalyzes the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis (PubMed:7794891).
Involvement in disease
Gastrointestinal ulceration, recurrent, with dysfunctional platelets
GURDP
An autosomal recessive disorder characterized by recurrent gastrointestinal mucosal ulcers, gastrointestinal bleeding, chronic anemia, iron deficiency, and abdominal pain. Disease features also include platelet dysfunction, and globally decreased eicosanoid synthesis.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Membrane lipid metabolism; glycerophospholipid metabolism.
Lipid metabolism; arachidonate metabolism.
Lipid metabolism; prostaglandin biosynthesis.
Lipid metabolism; leukotriene B4 biosynthesis.
Post-translational modifications
Phosphorylated at both Ser-505 and Ser-727 in response to mitogenic stimuli.
Tissue Specificity
Expressed in various cells and tissues such as macrophages, neutrophils, fibroblasts and lung endothelium. Expressed in platelets (at protein level) (PubMed:25102815).
Cellular localization
- Cytoplasm
- Golgi apparatus membrane
- Nucleus envelope
- Translocates to intracellular membranes in a calcium-dependent way.
Alternative names
CPLA2, PLA2G4, PLA2G4A, Cytosolic phospholipase A2, cPLA2, Phospholipase A2 group IVA
Database links
Other research areas
- Oncology