Recombinant Human Phospholipase A2 group V (PLA2G5)

Function

Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids (PubMed:8300559). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity), preferentially releasing fatty acyl groups with a low degree of unsaturation such as oleoyl (C18:1) and linoleoyl (C18:2) groups (PubMed:14998370, PubMed:23533611, PubMed:8300559). Hydrolyzes low-density lipoprotein (LDL) phospholipids releasing unsaturated fatty acids that drive macrophage polarization toward an M2 phenotype (By similarity). May act in an autocrine and paracrine manner. Contributes to lipid remodeling of cellular membranes at different subcellular locations and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of cardiolipin, a major component of the inner membrane of mitochondria and bacterial membranes (PubMed:23533611). Promotes phagocytosis of bacteria in macrophages through production of lysophosphatidylethanolamines (PubMed:25725101). Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:11694541). Promotes phagocytosis and killing of ingested fungi likely through controlling phagosome-lysosome fusion and phagosome maturation (By similarity). Plays a role in biosynthesis of cysteinyl leukotrienes (CysLTs) in myeloid cells (PubMed:12124392, PubMed:12796497). In eosinophils, triggers perinuclear arachidonate release and LTC4 synthesis in a PLA2G4A-independent way (PubMed:12796497). In neutrophils, amplifies CysLTs biosynthesis initiated by PLA2G4A (PubMed:12124392). Promotes immune complex clearance in macrophages via stimulating synthesis of CysLTs, which act through CYSLTR1 to trigger phagocytosis (By similarity). May regulate antigen processing in antigen-presenting cells (By similarity). In pulmonary macrophages regulates IL33 production required for activation of group 2 innate lymphoid cells (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (PubMed:14998370)

Subcellular Location

Secreted; Cell membrane; Cytoplasmic vesicle, phagosome; Recycling endosome; Golgi apparatus, cis-Golgi network; Golgi apparatus, trans-Golgi network

Disease Association

Fleck retina, familial benign (FRFB) : An autosomal recessive condition associated with a distinctive retinal appearance and no apparent visual or electrophysiologic deficits. Affected individuals are asymptomatic, but fundus examination reveals a striking pattern of diffuse, yellow-white, fleck-like lesions extending to the far periphery of the retina but sparing the foveal region. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Heart, placenta and less abundantly, in lung. Detected in the outer and inner plexiform layers of the retina (at protein level) (PubMed:22137173). Expressed in monocytes and macrophages (PubMed:25725101)

Pathway

Lipid metabolism; leukotriene C4 biosynthesis

• Chen J. et al. Cloning and recombinant expression of a novel human low molecular weight Ca(2+)-dependent phospholipase A2. — J. Biol. Chem. (1994)
• PubMed: CI-86AL9GH7VDJIK (JAN-)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Koduri R.S. et al. Bactericidal properties of human and murine groups I, II, V, X, and XII secreted phospholipases A(2). — J. Biol. Chem. (2002)
• Kim Y.J. et al. Group V phospholipase A2 induces leukotriene biosynthesis in human neutrophils through the activation of group IVA phospholipase A2. — J. Biol. Chem. (2002)
• Munoz N.M. et al. Human group V phospholipase A2 induces group IVA phospholipase A2-independent cysteinyl leukotriene synthesis in human eosinophils. — J. Biol. Chem. (2003)
• Sun Y.X. et al. Biosynthesis of anandamide and N-palmitoylethanolamine by sequential actions of phospholipase A2 and lysophospholipase D. — Biochem. J. (2004)