PLA2G6
Domain
Has two putative calmodulin binding domains, the 1-9-14 and IQ motifs. One calmodulin molecule interacts with PLA2G6 dimer, likely through 1-9-14 motif on each monomer (By similarity). Binds calmodulin in a calcium-dependent way (By similarity).
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 (PubMed:10092647, PubMed:10336645, PubMed:20886109, PubMed:9417066). 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.
Involvement in disease
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Tissue Specificity
Four different transcripts were found to be expressed in a distinct tissue distribution.
Cellular localization
- Cytoplasm
- Cell membrane
- Mitochondrion
- Cell projection
- Pseudopodium
- Recruited to the membrane-enriched pseudopods upon MCP1/CCL2 stimulation in monocytes.
Alternative names
PLPLA9, PLA2G6, 85/88 kDa calcium-independent phospholipase A2, CaI-PLA2, 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, GVI PLA2, iPLA2-beta, PNPLA9