FPR2

N-formyl peptide receptor 2

Pattern recognition G protein-coupled receptor (GPCR) that recognizes peptides with N-terminal formyl methionine, which are derived from invading pathogens or host mitochondria as pathogen or damage-associated molecular patterns (PAMPs and DAMPs) (PubMed:1374236, PubMed:25605714, PubMed:35217703). Preferentially recognizes longer peptides or peptides with specific sequences such as the phenol-soluble modulin (PSM) family of formylated peptide toxins produced by Staphylococcus aureus (PubMed:30098280). Ligand binding causes a conformation change that triggers signaling via G(i)/GNAI1 inhibiting adenylate cyclase activity, leading to decreased intracellular cAMP levels (PubMed:40080544). In addition, can recognize a variety of chemically distinct endogenous ligands including proteins and lipids besides formylpeptides and thereby plays multiple roles in inflammation. Acts as a receptor for the chemokine-like protein FAM19A5, mediating FAM19A5-stimulated macrophage chemotaxis and the inhibitory effect on TNFSF11/RANKL-induced osteoclast differentiation (By similarity). Acts also as a ceramide membrane receptor, and long-chain ceramides (C14 to C20) binding induces conformational changes that inhibits diet-induced adipose thermogenesis (PubMed:40080544). Participates in neuroprotection via interaction with humanin/MT-RNR2 and Amyloid-beta protein 42, product of APP (PubMed:11689470, PubMed:35365641). Differential signaling is also defined by receptor oligomerization state. Binding of ANXA1 to FPR2 homodimer elicits activation of p38 MAPKinase pathway leading to HSPB1/HSP27 phosphorylation and IL10 production in monocytes. Whereas agonistic activation of FPR1:FPR2 heterodimers signals a proapoptotic JNK pathway in neutrophils