Recombinant Mouse Formyl peptide receptor 2 (Fpr2), partial

Function

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:10477558, PubMed:12218158, PubMed:19387439, PubMed:25605714). 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 (By similarity). Ligand binding causes a conformation change that triggers signaling via G(i)/GNAI1 inhibiting adenylate cyclase activity, leading to decreased intracellular cAMP levels. In addition, can recognize a variety of chemically distinct endogenous ligands including proteins and lipids besides formylpeptides and thereby plays multiple roles in inflammation (PubMed:10477558, PubMed:19497865, PubMed:37056936). 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 (PubMed:29138422). Acts also as a ceramide membrane receptor, and long-chain ceramides (C14 to C20) binding induces conformational changes that inhibits diet-induced adipose thermogenesis (By similarity). May participate in neuroprotection via interaction with MT-RNR2 and Amyloid-beta protein 42, product of APP (By similarity). 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 (By similarity)

Subcellular Location

Cell membrane (Multi-pass membrane protein)

Tissue Specificity

Primarily expressed in neutrophils. Not detected in vomeronasal neurons

Subunit

Homodimer; the homodimerization is potentiated in response to the anti-inflammatory agonist ANXA1 and inhibited upon binding of pro-inflammatory agonist serum amyloid A (By similarity). Heterodimer with FPR1; the heterodimerization with FPR1 is potentiated in response to anti-inflammatory agonists such as lipoxin A4, ANXA1 and Ac2-26 ANXA1 peptide (By similarity). Forms a complex with heterotrimeric G(i) protein composed of GNAI1, GNB1 and GNG2 subunits (By similarity). Interacts with Amyloid-beta protein 42, product of APP; the interaction takes place at the cell surface and the complex is then rapidly internalized (By similarity). Interacts with S1PR4 (PubMed:37056936). Interacts with GNAI1. Interacts with humanin/MT-RNR2 (By similarity). Interacts with GNAI2 (By similarity)

• Gao J.-L. et al. Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse. — Genomics (1998)
• Vaughn M.W. et al. Identification, cloning, and functional characterization of a murine lipoxin A4 receptor homologue gene. — J. Immunol. (2002)
• Mural R.J. et al. PubMed: CI-70VOHH7BF94TO (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Hartt J.K. et al. N-formylpeptides induce two distinct concentration optima for mouse neutrophil chemotaxis by differential interaction with two N-formylpeptide receptor (FPR) subtypes. Molecular characterization of FPR2, a second mouse neutrophil FPR. — J. Exp. Med. (1999)
• Kurosaka K. et al. Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant. — J. Immunol. (2005)
• Gao J.L. et al. F2L, a peptide derived from heme-binding protein, chemoattracts mouse neutrophils by specifically activating Fpr2, the low-affinity N-formylpeptide receptor. — J. Immunol. (2007)
• Riviere S. et al. Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors. — Nature (2009)