PLA2G4A

PLA2G4A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1BCI, 1CJY, 1RLW
Identifiers
Aliases	PLA2G4A, PLA2G4, cPLA2-alpha, cPLA2, phospholipase A2 group IVA
External IDs	MGI: 1195256 HomoloGene: 32059 GeneCards: PLA2G4A
Genetically Related Diseases
epilepsy[1]
Gene ontology Molecular function • metal ion binding • calcium ion binding • hydrolase activity • calcium-dependent phospholipid binding • phospholipase activity • histone acetyltransferase binding • phospholipase A2 activity • calcium-dependent phospholipase A2 activity • phosphatidylcholine 1-acylhydrolase activity • lysophospholipase activity Cellular component • cytoplasm • Golgi apparatus • nucleus • intracellular membrane-bounded organelle • cytoplasmic, membrane-bounded vesicle • endoplasmic reticulum • perinuclear region of cytoplasm • endoplasmic reticulum membrane • zymogen granule • cytoplasmic vesicle • mitochondrial inner membrane • cytosol Biological process • phospholipid metabolic process • luteolysis • response to hormone • positive regulation of vesicle fusion • phosphatidylinositol acyl-chain remodeling • platelet activating factor biosynthetic process • arachidonic acid secretion • icosanoid metabolic process • lipid metabolic process • response to lipopolysaccharide • phosphatidylserine acyl-chain remodeling • phospholipid catabolic process • phosphatidylglycerol acyl-chain remodeling • cellular response to antibiotic • response to calcium ion • lipid catabolic process • phosphatidic acid biosynthetic process • positive regulation of bone mineralization • positive regulation of inflammatory response • phosphatidylcholine acyl-chain remodeling • metabolic process • regulation of cell proliferation • positive regulation of prostaglandin biosynthetic process • phosphatidylethanolamine acyl-chain remodeling • response to vitamin D • ovulation from ovarian follicle • surfactant homeostasis • positive regulation of apoptotic process • positive regulation of cell proliferation • response to glucocorticoid • aging • response to organonitrogen compound • decidualization • response to methylmercury • cardiolipin acyl-chain remodeling • response to heat • response to organic substance • positive regulation of fever generation • icosanoid biosynthetic process • response to hydrogen peroxide • response to lithium ion • arachidonic acid metabolic process 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_024420	NM_008869 NM_001305632
RefSeq (protein)	NP_001298122.1 NP_077734.1	NP_032895.1
Location (UCSC)	Chr 1: 186.83 – 186.99 Mb	Chr 1: 149.83 – 149.96 Mb
PubMed search	[2]	[3]
Wikidata

View/Edit Human

View/Edit Mouse

Cytosolic phospholipase A2 is an enzyme that in humans is encoded by the PLA2G4A gene.^[4][5]

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.^[5]

Interactions

PLA2G4A has been shown to interact with HTATIP.^[6]

Clinical signficance

Mutations in this gene have been associated with multifocal stenosing ulceration of the small intestine.^[7]

References

1. "Diseases that are genetically associated with PLA2G4A view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. Dennis EA (Jun 1994). "Diversity of group types, regulation, and function of phospholipase A2". J Biol Chem. 269 (18): 13057–60. PMID 8175726.
5. "Entrez Gene: PLA2G4A phospholipase A2, group IVA (cytosolic, calcium-dependent)".
6. 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.
7. 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.