PLA2G6

Phospholipase A2, group VI (cytosolic, calcium-independent)
Identifiers
Symbols	PLA2G6 ; CaI-PLA2; GVI; INAD1; IPLA2-VIA; NBIA2; NBIA2A; NBIA2B; PARK14; PLA2; PNPLA9; iPLA2; iPLA2beta
External IDs	OMIM: 603604 MGI: 1859152 HomoloGene: 2635 ChEMBL: 3213 GeneCards: PLA2G6 Gene
EC number	3.1.1.4
Gene ontology Molecular function • phospholipase A2 activity • calmodulin binding Cellular component • extracellular space • cytoplasm • microtubule organizing center • cytosol • membrane Biological process • phospholipid metabolic process • chemotaxis • lipid catabolic process • antibacterial humoral response • cardiolipin biosynthetic process • cardiolipin acyl-chain remodeling • phosphatidylcholine acyl-chain remodeling • phosphatidylethanolamine acyl-chain remodeling • Fc-gamma receptor signaling pathway involved in phagocytosis • small molecule metabolic process • innate immune response • glycerophospholipid biosynthetic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8398	53357
Ensembl	ENSG00000184381	ENSMUSG00000042632
UniProt	O60733	P97819
RefSeq (mRNA)	NM_001004426	NM_001199023
RefSeq (protein)	NP_001004426	NP_001185952
Location (UCSC)	Chr 22: 38.11 – 38.21 Mb	Chr 15: 79.29 – 79.33 Mb
PubMed search

85 kDa calcium-independent phospholipase A2 is an enzyme that in humans is encoded by the PLA2G6 gene.^[1][2][3][4]

Function

The protein encoded by this gene is a phospholipase A2 enzyme, a subclass of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, Fas receptor-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only two of them have been determined to date.^[4]

Model organisms

Model organisms have been used in the study of PLA2G6 function. A conditional knockout mouse line called Pla2g6^{tm1a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.^[5] Male and female animals underwent a standardized phenotypic screen^[6] to determine the effects of deletion.^{[7][8][9][10]} Additional screens performed: - In-depth immunological phenotyping^[11]

Pla2g6 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[6][11]
Homozygous viability at P14	Normal
Homozygous Fertility	Abnormal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Trichuris Challenge	Normal

References

1. Larsson PK, Claesson HE, Kennedy BP (Jan 1998). "Multiple splice variants of the human calcium-independent phospholipase A2 and their effect on enzyme activity". The Journal of Biological Chemistry 273 (1): 207–14. doi:10.1074/jbc.273.1.207. PMID 9417066.
2. Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ (Sep 2006). "Characterization of the human patatin-like phospholipase family". Journal of Lipid Research 47 (9): 1940–9. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.
3. Kienesberger PC, Oberer M, Lass A, Zechner R (Apr 2009). "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". Journal of Lipid Research. 50 Suppl: S63–8. doi:10.1194/jlr.R800082-JLR200. PMC 2674697. PMID 19029121.
4. "Entrez Gene: PLA2G6 phospholipase A2, group VI (cytosolic, calcium-independent)".
5. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
6. "International Mouse Phenotyping Consortium".
7. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
8. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
9. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
10. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
11. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

• Schröder HC, Perovic S, Kavsan V, Ushijima H, Müller WE (1998). "Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death". Neurotoxicology 19 (4-5): 683–8. PMID 9745929.
• Leslie CC (Feb 2004). "Regulation of arachidonic acid availability for eicosanoid production". Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire 82 (1): 1–17. doi:10.1139/o03-080. PMID 15052324.
• Turk J, Ramanadham S (Oct 2004). "The expression and function of a group VIA calcium-independent phospholipase A2 (iPLA2beta) in beta-cells". Canadian Journal of Physiology and Pharmacology 82 (10): 824–32. doi:10.1139/y04-064. PMID 15573142.
• Law MH, Cotton RG, Berger GE (Jun 2006). "The role of phospholipases A2 in schizophrenia". Molecular Psychiatry 11 (6): 547–56. doi:10.1038/sj.mp.4001819. PMID 16585943.
• Tang J, Kriz RW, Wolfman N, Shaffer M, Seehra J, Jones SS (Mar 1997). "A novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs". The Journal of Biological Chemistry 272 (13): 8567–75. doi:10.1074/jbc.272.13.8567. PMID 9079687.
• Mavoungou E, Georges-Courbot MC, Poaty-Mavoungou V, Nguyen HT, Yaba P, Delicat A, Georges AJ, Russo-Marie F (Sep 1997). "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. doi:10.1097/00042560-199709010-00001. PMID 9377118.
• Ma Z, Wang X, Nowatzke W, Ramanadham S, Turk J (Apr 1999). "Human pancreatic islets express mRNA species encoding two distinct catalytically active isoforms of group VI phospholipase A2 (iPLA2) that arise from an exon-skipping mechanism of alternative splicing of the transcript from the iPLA2 gene on chromosome 22q13.1". The Journal of Biological Chemistry 274 (14): 9607–16. doi:10.1074/jbc.274.14.9607. PMID 10092647.
• Larsson Forsell PK, Kennedy BP, Claesson HE (Jun 1999). "The human calcium-independent phospholipase A2 gene multiple enzymes with distinct properties from a single gene". European Journal of Biochemistry / FEBS 262 (2): 575–85. doi:10.1046/j.1432-1327.1999.00418.x. PMID 10336645.
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (Dec 1999). "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
• Kim SJ, Gershov D, Ma X, Brot N, Elkon KB (Sep 2002). "I-PLA(2) activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation". The Journal of Experimental Medicine 196 (5): 655–65. doi:10.1084/jem.20020542. PMC 2194002. PMID 12208880.
• Hichami A, Joshi B, Simonin AM, Khan NA (Nov 2002). "Role of three isoforms of phospholipase A2 in capacitative calcium influx in human T-cells". European Journal of Biochemistry / FEBS 269 (22): 5557–63. doi:10.1046/j.1432-1033.2002.03261.x. PMID 12423354.
• Cummings BS, McHowat J, Schnellmann RG (Mar 2004). "Role of an endoplasmic reticulum Ca2+-independent phospholipase A2 in cisplatin-induced renal cell apoptosis". The Journal of Pharmacology and Experimental Therapeutics 308 (3): 921–8. doi:10.1124/jpet.103.060541. PMID 14634037.
• Bao S, Jin C, Zhang S, Turk J, Ma Z, Ramanadham S (Feb 2004). "Beta-cell calcium-independent group VIA phospholipase A(2) (iPLA(2)beta): tracking iPLA(2)beta movements in response to stimulation with insulin secretagogues in INS-1 cells". Diabetes. 53 Suppl 1 (90001): S186–9. doi:10.2337/diabetes.53.2007.S186. PMID 14749286.
• Tay HK, Melendez AJ (May 2004). "Fcgamma RI-triggered generation of arachidonic acid and eicosanoids requires iPLA2 but not cPLA2 in human monocytic cells". The Journal of Biological Chemistry 279 (21): 22505–13. doi:10.1074/jbc.M308788200. PMID 15007079.
• Tanaka H, Minakami R, Kanaya H, Sumimoto H (Aug 2004). "Catalytic residues of group VIB calcium-independent phospholipase A2 (iPLA2gamma)". Biochemical and Biophysical Research Communications 320 (4): 1284–90. doi:10.1016/j.bbrc.2004.05.225. PMID 15249229.