PLA2G6

PLA2G6 is an A2 phospholipase, a class 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-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells.

Phospholipase A2 group VI

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 (PubMed:9417066, PubMed:10092647, PubMed:10336645, PubMed:20886109).
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 (PubMed:10092647, PubMed:10336645, PubMed:20886109).
Can further hydrolyze lysophospholipids carrying saturated fatty acyl chains (lysophospholipase activity) (PubMed:20886109).
Upon oxidative stress, contributes to remodeling of mitochondrial phospholipids in pancreatic beta cells, in a repair mechanism to reduce oxidized lipid content (PubMed:23533611).
Preferentially hydrolyzes oxidized polyunsaturated fatty acyl chains from cardiolipins, yielding monolysocardiolipins that can be reacylated with unoxidized fatty acyls to regenerate native cardiolipin species (By similarity).
Hydrolyzes oxidized glycerophosphoethanolamines present in pancreatic islets, releasing oxidized polyunsaturated fatty acids such as hydroxyeicosatetraenoates (HETEs) (By similarity).
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 (PubMed:20886109).
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 (By similarity).
Regulates F-actin polymerization at the pseudopods, which is required for both speed and directionality of MCP1/CCL2-induced monocyte chemotaxis (PubMed:18208975).
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 (By similarity).
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 (By similarity).
In response to glucose, amplifies calcium influx in pancreatic beta cells to promote INS secretion (By similarity).
Isoform Ankyrin-iPLA2-1
Lacks the catalytic domain and may act as a negative regulator of the catalytically active isoforms.
Isoform Ankyrin-iPLA2-2
Lacks the catalytic domain and may act as a negative regulator of the catalytically active isoforms.

Antibacterial humoral responseManual Assertion Based On ExperimentIDA:UniProtKB
Cardiolipin acyl-chain remodelingManual Assertion Based On ExperimentIDA:UniProtKB
Cardiolipin biosynthetic processManual Assertion Based On ExperimentIMP:UniProtKB
ChemotaxisIEA:UniProtKB-KW
Fc-gamma receptor signaling pathway involved in phagocytosisTAS:Reactome
Maternal process involved in female pregnancyIEA:Ensembl
MemoryIEA:Ensembl
Negative regulation of synaptic transmission, glutamatergicIEA:Ensembl
Phosphatidic acid metabolic processISS:UniProtKB
Phosphatidylcholine catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Phosphatidylethanolamine catabolic processISS:UniProtKB
Platelet activating factor metabolic processISS:UniProtKB
Positive regulation of arachidonic acid secretionIEA:Ensembl
Positive regulation of ceramide biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of cytosolic calcium ion concentrationIEA:Ensembl
Positive regulation of exocytosisIEA:Ensembl
Positive regulation of insulin secretion involved in cellular response to glucose stimulusISS:UniProtKB
Positive regulation of protein kinase C signalingIEA:Ensembl
Positive regulation of protein phosphorylationIEA:Ensembl
Positive regulation of release of cytochrome c from mitochondriaIEA:Ensembl
Regulation of store-operated calcium channel activityIEA:Ensembl
Response to endoplasmic reticulum stressIEA:Ensembl
Urinary bladder smooth muscle contractionIEA:Ensembl
VasodilationIEA:Ensembl

Cytoplasm
Cell membrane
Mitochondrion
Cell projection, pseudopodium
Recruited to the membrane-enriched pseudopods upon MCP1/CCL2 stimulation in monocytes.

Neurodegeneration with brain iron accumulation 2B (NBIA2B):
A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. It is characterized by progressive extrapyramidal dysfunction leading to rigidity, dystonia, dysarthria and sensorimotor impairment.
Neurodegeneration with brain iron accumulation 2A (NBIA2A):
A neurodegenerative disease characterized by pathologic axonal swelling and spheroid bodies in the central nervous system. Onset is within the first 2 years of life with death by age 10 years.
Parkinson disease 14 (PARK14):
An adult-onset progressive neurodegenerative disorder characterized by parkinsonism, dystonia, severe cognitive decline, cerebral and cerebellar atrophy and absent iron in the basal ganglia on magnetic resonance imaging.