PLA2G2A
Description
The PLA2G2A (phospholipase A2 group IIA) is a protein-coding gene located on chromosome 1.
Phospholipase A2, membrane associated is an enzyme that in humans is encoded by the PLA2G2A gene.
PLA2G2A, also known as GIIC sPLA2, Group IIA phospholipase A2, Non-pancreatic secretory phospholipase A2, and Phosphatidylcholine 2-acylhydrolase 2A, is a secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids. It plays a role in host antimicrobial defense, inflammatory response, and tissue regeneration. PLA2G2A hydrolyzes the ester bond of the fatty acyl group attached at the sn-2 position of phospholipids, with a preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines. This activity contributes to lipid remodeling of cellular membranes and the generation of lipid mediators involved in pathogen clearance. PLA2G2A exhibits bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane. In sterile inflammation, PLA2G2A targets membrane phospholipids of extracellular mitochondria released from activated platelets, generating free unsaturated fatty acids like arachidonate that are used by neighboring leukocytes to synthesize inflammatory eicosanoids such as leukotrienes. This process also compromises mitochondrial membrane integrity, promoting the release of damage-associated molecular pattern molecules that activate the innate immune response. PLA2G2A acts as a stem cell regulator in the intestinal crypt, mediating Paneth cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling in intestinal stem cells. Upon inflammation, PLA2G2A is secreted into the intestinal lumen, promoting prostaglandin E2 synthesis through an autocrine mechanism and stimulating Wnt signaling in intestinal stem cells, leading to tissue regeneration. PLA2G2A may also play a role in the biosynthesis of N-acyl ethanolamines, which regulate energy metabolism and inflammation. It hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved to release N-acyl ethanolamines. Independent of its catalytic activity, PLA2G2A acts as a ligand for integrins. It binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1, and ITGA5:ITGB1, inducing integrin conformational changes and enhanced ligand binding. This interaction induces cell proliferation in an integrin-dependent manner.
PLA2G2A is also known as MOM1, PLA2, PLA2B, PLA2L, PLA2S, PLAS1, sPLA2.
