PLA2G4A explained

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.

Interactions

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

Clinical significance

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

Further reading

• Schröder HC, Perovic S, Kavsan V, etal . Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death . Neurotoxicology . 19 . 4–5 . 683–688 . 1998 . 9745929 .
• Hirabayashi T, Murayama T, Shimizu T . Regulatory mechanism and physiological role of cytosolic phospholipase A2 . Biological and Pharmaceutical Bulletin . 27 . 8 . 1168–1173 . 2005 . 15305015 . 10.1248/bpb.27.1168 . free .
• Law MH, Cotton RG, Berger GE . The role of phospholipases A2 in schizophrenia . Molecular Psychiatry . 11 . 6 . 547–556 . 2006 . 16585943 . 10.1038/sj.mp.4001819 . free .
• Shimizu T, Ohto T, Kita Y . Cytosolic phospholipase A2: biochemical properties and physiological roles . IUBMB Life . 58 . 5–6 . 328–333 . 2006 . 16754327 . 10.1080/15216540600702289 . 36287675 .
• Sharp JD, White DL, Chiou XG, etal . Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2 . Journal of Biological Chemistry . 266 . 23 . 14850–14853 . 1991 . 10.1016/S0021-9258(18)98550-9 . 1869522 . free .
• Clark JD, Lin LL, Kriz RW, etal . A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP . Cell . 65 . 6 . 1043–1051 . 1991 . 1904318 . 10.1016/0092-8674(91)90556-E . 134332 .
• Tay A, Simon JS, Squire J, etal . Cytosolic phospholipase A2 gene in human and rat: chromosomal localization and polymorphic markers . Genomics . 26 . 1 . 138–141 . 1995 . 7782073 . 10.1016/0888-7543(95)80093-2 .
• Wu T, Ikezono T, Angus CW, Shelhamer JH . Characterization of the promoter for the human 85 kDa cytosolic phospholipase A2 gene . Nucleic Acids Research . 22 . 23 . 5093–5098 . 1995 . 7800505 . 10.1093/nar/22.23.5093 . 523783 .
• Miyashita A, Crystal RG, Hay JG . 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 Research . 23 . 2 . 293–301 . 1995 . 7862535 . 10.1093/nar/23.2.293 . 306668 .
• Morri H, Ozaki M, Watanabe Y . 5'-flanking region surrounding a human cytosolic phospholipase A2 gene . Biochemical and Biophysical Research Communications . 205 . 1 . 6–11 . 1995 . 7999086 . 10.1006/bbrc.1994.2621 .
• Sharp JD, Pickard RT, Chiou XG, etal . Serine 228 is essential for catalytic activities of 85-kDa cytosolic phospholipase A2 . Journal of Biological Chemistry . 269 . 37 . 23250–23254 . 1994 . 10.1016/S0021-9258(17)31645-9 . 8083230 . free .
• Lin LL, Wartmann M, Lin AY, etal . cPLA2 is phosphorylated and activated by MAP kinase . Cell . 72 . 2 . 269–78 . 1993 . 8381049 . 10.1016/0092-8674(93)90666-E . 1500909 .
• Flati V, Haque SJ, Williams BR . Interferon-alpha-induced phosphorylation and activation of cytosolic phospholipase A2 is required for the formation of interferon-stimulated gene factor three . EMBO Journal . 15 . 7 . 1566–1571 . 1996 . 8612580 . 10.1002/j.1460-2075.1996.tb00501.x. 450066 .
• de Carvalho MG, McCormack AL, Olson E, etal . Identification of phosphorylation sites of human 85-kDa cytosolic phospholipase A2 expressed in insect cells and present in human monocytes . Journal of Biological Chemistry . 271 . 12 . 6987–6997 . 1996 . 8636128 . 10.1074/jbc.271.12.6987 . free .
• Freed KA, Moses EK, Brennecke SP, Rice GE . Differential expression of type II, IV and cytosolic PLA2 messenger RNA in human intrauterine tissues at term . Molecular Human Reproduction . 3 . 6 . 493–499 . 1997 . 9239738 . 10.1093/molehr/3.6.493 . free .
• Mavoungou E, Georges-Courbot MC, Poaty-Mavoungou V, etal . HIV and SIV envelope glycoproteins induce phospholipase A2 activation in human and macaque lymphocytes . Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology . 16 . 1 . 1–9 . 1997 . 9377118 . 10.1097/00042560-199709010-00001 . free .
• Perisic O, Fong S, Lynch DE, etal . Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2 . Journal of Biological Chemistry . 273 . 3 . 1596–1604 . 1998 . 9430701 . 10.1074/jbc.273.3.1596 . free .
• Börsch-Haubold AG, Bartoli F, Asselin J, etal . Identification of the phosphorylation sites of cytosolic phospholipase A2 in agonist-stimulated human platelets and HeLa cells . Journal of Biological Chemistry . 273 . 8 . 4449–4458 . 1998 . 9468497 . 10.1074/jbc.273.8.4449 . free .

Notes and References

1. Dennis EA . Diversity of group types, regulation, and function of phospholipase A2 . Journal of Biological Chemistry . 269 . 18 . 13057–13060 . Jun 1994 . 10.1016/S0021-9258(17)36794-7 . 8175726 . free .
2. Web site: 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 . PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production . Molecular and Cellular Biology . 21 . 14 . 4470–4481 . July 2001 . 11416127 . 87107 . 10.1128/MCB.21.14.4470-4481.2001 .
4. Brooke MA, Longhurst HJ, Plagnol V, Kirkby NS, Mitchell JA, Rüschendorf F, Warner TD, Kelsell DP, Macdonald TT . Cryptogenic multifocal ulcerating stenosing enteritis associated with homozygous deletion mutations in cytosolic phospholipase A2-α . Gut . 63. 1. 96–104. December 2012 . 23268370 . 10.1136/gutjnl-2012-303581 . 206957682 .