General Information of the Ferroptosis Regulator (ID: REG10037)
Regulator Name 85/88 kDa calcium-independent phospholipase A2 (PLA2G6)
Synonyms
PLPLA9; 2-lysophosphatidylcholine acylhydrolase; Group VI phospholipase A2; Intracellular membrane-associated calcium-independent phospholipase A2 beta; Palmitoyl-CoA hydrolase; Patatin-like phospholipase domain-containing protein 9
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Gene Name PLA2G6
Gene ID 8398
Regulator Type Protein coding
Uniprot ID O60733
Sequence
MQFFGRLVNTFSGVTNLFSNPFRVKEVAVADYTSSDRVREEGQLILFQNTPNRTWDCVLV
NPRNSQSGFRLFQLELEADALVNFHQYSSQLLPFYESSPQVLHTEVLQHLTDLIRNHPSW
SVAHLAVELGIRECFHHSRIISCANCAENEEGCTPLHLACRKGDGEILVELVQYCHTQMD
VTDYKGETVFHYAVQGDNSQVLQLLGRNAVAGLNQVNNQGLTPLHLACQLGKQEMVRVLL
LCNARCNIMGPNGYPIHSAMKFSQKGCAEMIISMDSSQIHSKDPRYGASPLHWAKNAEMA
RMLLKRGCNVNSTSSAGNTALHVAVMRNRFDCAIVLLTHGANADARGEHGNTPLHLAMSK
DNVEMIKALIVFGAEVDTPNDFGETPTFLASKIGRLVTRKAILTLLRTVGAEYCFPPIHG
VPAEQGSAAPHHPFSLERAQPPPISLNNLELQDLMHISRARKPAFILGSMRDEKRTHDHL
LCLDGGGVKGLIIIQLLIAIEKASGVATKDLFDWVAGTSTGGILALAILHSKSMAYMRGM
YFRMKDEVFRGSRPYESGPLEEFLKREFGEHTKMTDVRKPKVMLTGTLSDRQPAELHLFR
NYDAPETVREPRFNQNVNLRPPAQPSDQLVWRAARSSGAAPTYFRPNGRFLDGGLLANNP
TLDAMTEIHEYNQDLIRKGQANKVKKLSIVVSLGTGRSPQVPVTCVDVFRPSNPWELAKT
VFGAKELGKMVVDCCTDPDGRAVDRARAWCEMVGIQYFRLNPQLGTDIMLDEVSDTVLVN
ALWETEVYIYEHREEFQKLIQLLLSP

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Function
Calcium-independent phospholipase involved in phospholipid remodeling with implications in cellular membrane homeostasis, mitochondrial integrity and signal transduction. Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 or sn-2 position of phospholipids (phospholipase A1 and A2 activity respectively), producing lysophospholipids that are used in deacylation-reacylation cycles. Hydrolyzes both saturated and unsaturated long fatty acyl chains in various glycerophospholipid classes such as phosphatidylcholines, phosphatidylethanolamines and phosphatidates, with a preference for hydrolysis at sn-2 position. Can further hydrolyze lysophospholipids carrying saturated fatty acyl chains (lysophospholipase activity). Upon oxidative stress, contributes to remodeling of mitochondrial phospholipids in pancreatic beta cells, in a repair mechanism to reduce oxidized lipid content. Preferentially hydrolyzes oxidized polyunsaturated fatty acyl chains from cardiolipins, yielding monolysocardiolipins that can be reacylated with unoxidized fatty acyls to regenerate native cardiolipin species. Hydrolyzes oxidized glycerophosphoethanolamines present in pancreatic islets, releasing oxidized polyunsaturated fatty acids such as hydroxyeicosatetraenoates (HETEs). Has thioesterase activity toward fatty-acyl CoA releasing CoA-SH known to facilitate fatty acid transport and beta- oxidation in mitochondria particularly in skeletal muscle. Plays a role in regulation of membrane dynamics and homeostasis. Selectively hydrolyzes sn-2 arachidonoyl group in plasmalogen phospholipids, structural components of lipid rafts and myelin. Regulates F-actin polymerization at the pseudopods, which is required for both speed and directionality of MCP1/CCL2-induced monocyte chemotaxis. Targets membrane phospholipids to produce potent lipid signaling messengers. Generates lysophosphatidate (LPA, 1-acyl-glycerol-3-phosphate), which acts via G-protein receptors in various cell types. Has phospholipase A2 activity toward platelet-activating factor (PAF, 1-O- alkyl-2-acetyl-sn-glycero-3-phosphocholine), likely playing a role in inactivation of this potent pro-inflammatory signaling lipid. In response to glucose, amplifies calcium influx in pancreatic beta cells to promote INS secretion.

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HGNC ID
HGNC:9039
KEGG ID hsa:8398
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PLA2G6 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Melanoma ICD-11: 2C30
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
Cell migration
Cell invasion
Cell metastasis
In Vitro Model
SK-MEL-28 cells Cutaneous melanoma Homo sapiens CVCL_0526
M14 cells Melanoma Homo sapiens CVCL_1395
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
A875 cells Melanoma Homo sapiens CVCL_4733
In Vivo Model
A total of 10 female BALB/c nude mice (4-6 weeks old) were supplied by Shanghai SLAC Laboratory Animal Co., Ltd (Shanghai, China). The nude mice were randomly divided into different treatment groups with five mice each, and maintained in a pathogen-free animal facility, followed by subcutaneously injection with 1 x 107 cells/mL M14 cells in 100 uL PBS on the right side to establish a subcutaneous xenograft model.

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Response regulation The GO and KEGG analysis suggested that the underlying mechanism of PLA2G6 in cutaneous malignant melanoma (CMM) might be associated with the ferroptosis pathway, and ferroptosis-related proteins were validated to be differentially expressed in PLA2G6 knockdown SK-MEL-28 and M14 cells. Together, PLA2G6 knockdown significantly inhibited cell proliferation, metastasis, and promoted apoptosis in melanoma.
Melanoma [ICD-11: 2C30]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator 85/88 kDa calcium-independent phospholipase A2 (PLA2G6) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
Cell migration
Cell invasion
Cell metastasis
In Vitro Model
SK-MEL-28 cells Cutaneous melanoma Homo sapiens CVCL_0526
M14 cells Melanoma Homo sapiens CVCL_1395
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
A875 cells Melanoma Homo sapiens CVCL_4733
In Vivo Model
A total of 10 female BALB/c nude mice (4-6 weeks old) were supplied by Shanghai SLAC Laboratory Animal Co., Ltd (Shanghai, China). The nude mice were randomly divided into different treatment groups with five mice each, and maintained in a pathogen-free animal facility, followed by subcutaneously injection with 1 x 107 cells/mL M14 cells in 100 uL PBS on the right side to establish a subcutaneous xenograft model.

    Click to Show/Hide
Response regulation The GO and KEGG analysis suggested that the underlying mechanism of PLA2G6 in cutaneous malignant melanoma (CMM) might be associated with the ferroptosis pathway, and ferroptosis-related proteins were validated to be differentially expressed in PLA2G6 knockdown SK-MEL-28 and M14 cells. Together, PLA2G6 knockdown significantly inhibited cell proliferation, metastasis, and promoted apoptosis in melanoma.
References
Ref 1 PLA2G6 Silencing Suppresses Melanoma Progression and Affects Ferroptosis Revealed by Quantitative Proteomics. Front Oncol. 2022 Mar 7;12:819235. doi: 10.3389/fonc.2022.819235. eCollection 2022.