PLA2G4A

Phospholipase A2, group IVA (cytosolic, calcium-dependent)
PDB rendering based on 1bci.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BCI​, 1CJY​, 1RLW​
Identifiers
Symbols	PLA2G4A ; PLA2G4; cPLA2; cPLA2-alpha
External IDs	OMIM: 600522 MGI: 1195256 HomoloGene: 32059 ChEMBL: 3816 GeneCards: PLA2G4A Gene
EC number	3.1.1.4, 3.1.1.5
Gene ontology Molecular function • lysophospholipase activity • phospholipase A2 activity • calcium ion binding • calcium-dependent phospholipid binding • calcium-dependent phospholipase A2 activity Cellular component • cytoplasm • mitochondrial inner membrane • endoplasmic reticulum membrane • Golgi apparatus • cytosol • cytoplasmic membrane-bounded vesicle Biological process • phospholipid metabolic process • phosphatidic acid biosynthetic process • platelet activating factor biosynthetic process • icosanoid metabolic process • blood coagulation • phospholipid catabolic process • arachidonic acid metabolic process • platelet activation • cardiolipin acyl-chain remodeling • phosphatidylglycerol acyl-chain remodeling • phosphatidylinositol acyl-chain remodeling • phosphatidylserine acyl-chain remodeling • phosphatidylcholine acyl-chain remodeling • phosphatidylethanolamine acyl-chain remodeling • regulation of cell proliferation • small molecule metabolic process • icosanoid biosynthetic process • glycerophospholipid biosynthetic process • arachidonic acid secretion • cellular response to antibiotic Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5321	18783
Ensembl	ENSG00000116711	ENSMUSG00000056220
UniProt	P47712	P47713
RefSeq (mRNA)	NM_001311193	NM_001305632
RefSeq (protein)	NP_001298122	NP_001292561
Location (UCSC)	Chr 1: 186.83 – 186.99 Mb	Chr 1: 149.83 – 149.96 Mb
PubMed search

Cytosolic phospholipase A2 is an enzyme that in humans is encoded by the PLA2G4A gene.^[1][2]

Function

This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandins and leukotrienes, are lipid-based cellular hormones that regulate hemodynamics, inflammatory responses, and other intracellular pathways. The hydrolysis reaction also produces lysophospholipids that are converted into platelet-activating factor. The enzyme is activated by increased intracellular Ca²⁺ levels and phosphorylation, resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles.^[2]

Interactions

PLA2G4A has been shown to interact with HTATIP.^[3]

Clinical signficance

Mutations in this gene have been associated with multifocal stenosing ulceration of the small intestine.^[4]

References

1. Dennis EA (Jun 1994). "Diversity of group types, regulation, and function of phospholipase A2". J Biol Chem 269 (18): 13057–60. PMID 8175726.
2. "Entrez Gene: PLA2G4A phospholipase A2, group IVA (cytosolic, calcium-dependent)".
3. Sheridan AM, Force T, Yoon HJ, O'Leary E, Choukroun G, Taheri MR, Bonventre JV (July 2001). "PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production". Mol. Cell. Biol. 21 (14): 4470–81. doi:10.1128/MCB.21.14.4470-4481.2001. PMC 87107. PMID 11416127.
4. Brooke MA, Longhurst HJ, Plagnol V, Kirkby NS, Mitchell JA, Rüschendorf F, Warner TD, Kelsell DP, Macdonald TT (December 2012). "Cryptogenic multifocal ulcerating stenosing enteritis associated with homozygous deletion mutations in cytosolic phospholipase A2-α". Gut 63: 96–104. doi:10.1136/gutjnl-2012-303581. PMID 23268370.

Further reading

• Schröder HC, Perovic S, Kavsan V, et al. (1998). "Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death". Neurotoxicology 19 (4–5): 683–8. PMID 9745929.
• Hirabayashi T, Murayama T, Shimizu T (2005). "Regulatory mechanism and physiological role of cytosolic phospholipase A2". Biol. Pharm. Bull. 27 (8): 1168–73. doi:10.1248/bpb.27.1168. PMID 15305015.
• Law MH, Cotton RG, Berger GE (2006). "The role of phospholipases A2 in schizophrenia". Mol. Psychiatry 11 (6): 547–56. doi:10.1038/sj.mp.4001819. PMID 16585943.
• Shimizu T, Ohto T, Kita Y (2006). "Cytosolic phospholipase A2: biochemical properties and physiological roles". IUBMB Life 58 (5–6): 328–33. doi:10.1080/15216540600702289. PMID 16754327.
• Sharp JD, White DL, Chiou XG, et al. (1991). "Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2". J. Biol. Chem. 266 (23): 14850–3. PMID 1869522.
• Clark JD, Lin LL, Kriz RW, et al. (1991). "A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP". Cell 65 (6): 1043–51. doi:10.1016/0092-8674(91)90556-E. PMID 1904318.
• Tay A, Simon JS, Squire J, et al. (1995). "Cytosolic phospholipase A2 gene in human and rat: chromosomal localization and polymorphic markers". Genomics 26 (1): 138–41. doi:10.1016/0888-7543(95)80093-2. PMID 7782073.
• Wu T, Ikezono T, Angus CW, Shelhamer JH (1995). "Characterization of the promoter for the human 85 kDa cytosolic phospholipase A2 gene". Nucleic Acids Res. 22 (23): 5093–8. doi:10.1093/nar/22.23.5093. PMC 523783. PMID 7800505.
• Miyashita A, Crystal RG, Hay JG (1995). "Identification of a 27 bp 5'-flanking region element responsible for the low level constitutive expression of the human cytosolic phospholipase A2 gene". Nucleic Acids Res. 23 (2): 293–301. doi:10.1093/nar/23.2.293. PMC 306668. PMID 7862535.
• Morri H, Ozaki M, Watanabe Y (1995). "5'-flanking region surrounding a human cytosolic phospholipase A2 gene". Biochem. Biophys. Res. Commun. 205 (1): 6–11. doi:10.1006/bbrc.1994.2621. PMID 7999086.
• Sharp JD, Pickard RT, Chiou XG, et al. (1994). "Serine 228 is essential for catalytic activities of 85-kDa cytosolic phospholipase A2". J. Biol. Chem. 269 (37): 23250–4. PMID 8083230.
• Lin LL, Wartmann M, Lin AY, et al. (1993). "cPLA2 is phosphorylated and activated by MAP kinase". Cell 72 (2): 269–78. doi:10.1016/0092-8674(93)90666-E. PMID 8381049.
• Flati V, Haque SJ, Williams BR (1996). "Interferon-alpha-induced phosphorylation and activation of cytosolic phospholipase A2 is required for the formation of interferon-stimulated gene factor three". EMBO J. 15 (7): 1566–71. PMC 450066. PMID 8612580.
• de Carvalho MG, McCormack AL, Olson E, et al. (1996). "Identification of phosphorylation sites of human 85-kDa cytosolic phospholipase A2 expressed in insect cells and present in human monocytes". J. Biol. Chem. 271 (12): 6987–97. doi:10.1074/jbc.271.12.6987. PMID 8636128.
• Freed KA, Moses EK, Brennecke SP, Rice GE (1997). "Differential expression of type II, IV and cytosolic PLA2 messenger RNA in human intrauterine tissues at term". Mol. Hum. Reprod. 3 (6): 493–9. doi:10.1093/molehr/3.6.493. PMID 9239738.
• Mavoungou E, Georges-Courbot MC, Poaty-Mavoungou V, et al. (1997). "HIV and SIV envelope glycoproteins induce phospholipase A2 activation in human and macaque lymphocytes". J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 16 (1): 1–9. doi:10.1097/00042560-199709010-00001. PMID 9377118.
• Perisic O, Fong S, Lynch DE, et al. (1998). "Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2". J. Biol. Chem. 273 (3): 1596–604. doi:10.1074/jbc.273.3.1596. PMID 9430701.
• Börsch-Haubold AG, Bartoli F, Asselin J, et al. (1998). "Identification of the phosphorylation sites of cytosolic phospholipase A2 in agonist-stimulated human platelets and HeLa cells". J. Biol. Chem. 273 (8): 4449–58. doi:10.1074/jbc.273.8.4449. PMID 9468497.