Protein: Phospholipase A2, membrane associated (EC 3.1.1.4) (GIIC sPLA2) (Group IIA phospholipase A2) (Phosphatidylcholine 2-acylhydrolase 2A) (P14423)
Organism: Rattus norvegicus (Rat)
Function: Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration (By similarity). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines. Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane. Upon sterile inflammation, targets membrane phospholipids of extracellular mitochondria released from activated platelets, generating free unsaturated fatty acids such as arachidonate that is used by neighboring leukocytes to synthesize inflammatory eicosanoids such as leukotrienes. Simultaneously, by compromising mitochondrial membrane integrity, promotes the release in circulation of potent damage-associated molecular pattern molecules that activate the innate immune response (By similarity). Plays a stem cell regulator role in the intestinal crypt. Within intracellular compartment mediates Paneth cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ICS). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ICS cells and tissue regeneration (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines. Independent of its catalytic activity, acts as a ligand for integrins. Binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1. Binds to a site (site 2) which is distinct from the classical ligand-binding site (site 1) and induces integrin conformational changes and enhanced ligand binding to site 1. Induces cell proliferation in an integrin-dependent manner (By similarity).
Subcellular location: Secreted {ECO:0000269|PubMed:2722857}. Cell membrane {ECO:0000269|PubMed:2722857}; Peripheral membrane protein {ECO:0000250|UniProtKB:P14555}. Mitochondrion outer membrane {ECO:0000250|UniProtKB:P14555}; Peripheral membrane protein {ECO:0000250|UniProtKB:P14555}.
Interaction partners:
- Group XIIA secretory phospholipase A2
- Polyunsaturated fatty acid lipoxygenase ALOX15
- Phospholipase A2, group III
- Group XIIB secretory phospholipase A2-like protein
- Polyunsaturated fatty acid 5-lipoxygenase
- Phospholipase A2
- Phospholipase A and acyltransferase 3
- Cytochrome P450 2E1
- Group 10 secretory phospholipase A2
- Group IIC secretory phospholipase A2
Sequence:
MKVLLLLAVVIMAFGSIQVQGSLLEFGQMILFKTGKRADVSYGFYGCHCGVGGRGSPKDATDWCCVTHDCCYNRLEKRGCGTKFLTYKFSYRGGQISCSTNQDSCRKQLCQCDKAAAECFARNKKSYSLKYQFYPNKFCKGKTPSC