Cytosolic phospholipase A2
Also known as: CPLA2, PLA2G4, PLA2G4A
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. 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). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway. In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids. 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. Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides. 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.
Classification
- Family (Pfam)
- PF00168 C2, PF01735 PLA2_B
- InterPro
- Acyl_Trfase/lysoPLipase, C2_cPLA2, C2_dom, C2_domain_sf, LysoPLipase_cat_dom
- Functional cluster
- Nucleotide & Amino-Acid Biosynthesis Enzymes
Experimental structures · PDB · 3
A predicted model is available from AlphaFold.
Gene Ontology · 33
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005783 endoplasmic reticulum
- GO:0005789 endoplasmic reticulum membrane
- GO:0005794 Golgi apparatus
- GO:0000139 Golgi membrane
- GO:0005743 mitochondrial inner membrane
- GO:0005635 nuclear envelope
- GO:0005634 nucleus
- GO:0004623 A2-type glycerophospholipase activity
- GO:0005509 calcium ion binding
- GO:0005544 calcium-dependent phospholipid binding
- GO:1902387 ceramide 1-phosphate binding
- GO:0008374 O-acyltransferase activity
- GO:0004622 phosphatidylcholine lysophospholipase A1 activity
- GO:0032266 phosphatidylinositol-3-phosphate binding
- GO:0070273 phosphatidylinositol-4-phosphate binding
- GO:0010314 phosphatidylinositol-5-phosphate binding
- GO:0019369 arachidonate metabolic process
- GO:0050482 arachidonate secretion
- GO:0006071 glycerol metabolic process
- GO:0046475 glycerophospholipid catabolic process
- GO:0006690 icosanoid metabolic process
- GO:0019370 leukotriene biosynthetic process
- GO:0006640 monoacylglycerol biosynthetic process
- GO:0036151 phosphatidylcholine acyl-chain remodeling
- GO:0034638 phosphatidylcholine catabolic process
- GO:0034478 phosphatidylglycerol catabolic process
- GO:0006663 platelet activating factor biosynthetic process
- GO:0043032 positive regulation of macrophage activation
- GO:0010572 positive regulation of platelet activation
- GO:0002827 positive regulation of T-helper 1 type immune response
- GO:0001516 prostaglandin biosynthetic process
Disease associations
Drugs targeting this protein · 1
- GIRIPLADIB inhibitor
Related proteins · sequence + function similarity
- Cytosolic phospholipase A2 1.00
- Cytosolic phospholipase A2 0.99
- Cytosolic phospholipase A2 0.99
- Cytosolic phospholipase A2 0.99
- Cytosolic phospholipase A2 0.99
- Cytosolic phospholipase A2 0.99
- Cytosolic phospholipase A2 0.99
- Cytosolic phospholipase A2 0.98
- Cytosolic phospholipase A2 0.98
- Cytosolic phospholipase A2 0.96
- Cytosolic phospholipase A2 gamma 0.69
- Cytosolic phospholipase A2 gamma 0.68
Co-cited proteins · studied together in the literature
- Cytosolic phospholipase A2 delta 1 shared papers
- Cytosolic phospholipase A2 1 shared papers
- Cytosolic phospholipase A2 beta 2 shared papers
- Prostaglandin G/H synthase 2 1 shared papers
- Cytosolic phospholipase A2 gamma 1 shared papers
- Histone acetyltransferase KAT5 1 shared papers
Literature · 35 cited papers
- Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
- Cyclooxygenase-2 Mediated Oxidation of 2-Arachidonoyl-Lysophospholipids Identifies Unknown Lipid Signaling Pathways. Cell Chem. Biol. · 2016
- Bleeding diathesis and gastro-duodenal ulcers in inherited cytosolic phospholipase-A2 alpha deficiency. Thromb. Haemost. · 2014
- Cryptogenic multifocal ulcerating stenosing enteritis associated with homozygous deletion mutations in cytosolic phospholipase A2-alpha. Gut · 2014
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
- Inherited human cPLA(2alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction. J. Clin. Invest. · 2008
- Phosphoproteome of resting human platelets. J. Proteome Res. · 2008
- Ceramide-1-phosphate binds group IVA cytosolic phospholipase a2 via a novel site in the C2 domain. J. Biol. Chem. · 2007
- … and 23 more in the literature graph