PLA2G5
Description
The PLA2G5 (phospholipase A2 group V) is a protein-coding gene located on chromosome 1.
Calcium-dependent phospholipase A2 is an enzyme that in humans is encoded by the PLA2G5 gene. This gene is a member of the secretory phospholipase A2 family. It is located in a tightly-linked cluster of secretory phospholipase A2 genes on chromosome 1. The encoded enzyme catalyzes the hydrolysis of membrane phospholipids to generate lysophospholipids and free fatty acids including arachidonic acid. It preferentially hydrolyzes linoleoyl-containing phosphatidylcholine substrates. Secretion of this enzyme is thought to induce inflammatory responses in neighboring cells. Alternatively spliced transcript variants have been found, but their full-length nature has not been determined.
PLA2G5 is a secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids. It hydrolyzes the ester bond of the fatty acyl group attached at the sn-2 position of phospholipids, preferentially releasing fatty acyl groups with a low degree of unsaturation such as oleoyl (C18:1) and linoleoyl (C18:2). PLA2G5 can hydrolyze low-density lipoprotein (LDL) phospholipids, releasing unsaturated fatty acids that drive macrophage polarization toward an M2 phenotype. It can act in an autocrine and paracrine manner. PLA2G5 contributes to lipid remodeling of cellular membranes at different subcellular locations and generation of lipid mediators involved in pathogen clearance. It cleaves sn-2 fatty acyl chains of cardiolipin, a major component of the inner membrane of mitochondria and bacterial membranes. PLA2G5 promotes phagocytosis of bacteria in macrophages through production of lysophosphatidylethanolamines and displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane. PLA2G5 promotes phagocytosis and killing of ingested fungi likely through controlling phagosome-lysosome fusion and phagosome maturation. It plays a role in the biosynthesis of cysteinyl leukotrienes (CysLTs) in myeloid cells. In eosinophils, PLA2G5 triggers perinuclear arachidonate release and LTC4 synthesis in a PLA2G4A-independent way. In neutrophils, PLA2G5 amplifies CysLTs biosynthesis initiated by PLA2G4A. It promotes immune complex clearance in macrophages via stimulating synthesis of CysLTs, which act through CYSLTR1 to trigger phagocytosis. PLA2G5 may regulate antigen processing in antigen-presenting cells. In pulmonary macrophages PLA2G5 regulates IL33 production required for activation of group 2 innate lymphoid cells. PLA2G5 may play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism. It hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines.
PLA2G5 is also known as FRFB, GV-PLA2, PLA2-10, hVPLA(2).
