The human receptor protein is encoded by the FPR2 gene and is activated to regulate cell function by binding any one of a wide variety of ligands including not only certain N-Formylmethionine-containing oligopeptides such as N-Formylmethionine-leucyl-phenylalanine (FMLP) but also the polyunsaturated fatty acid metabolite of arachidonic acid, lipoxin A4 (LXA4).

The FPR2 receptor is expressed on human neutrophils, eosinophils, monocytes, macrophages, T cells, synovial fibroblasts, and intestinal and airway epithelium.

[7] Many oligopeptides that possess an N-Formylmethionine N-terminal residue such as the prototypical tripeptide N-Formylmethionine-leucyl-phenylalanine (i.e. FMLP), are products of the protein synthesis conducted by bacteria.

However, a series of subsequent studies cloned two genes that encoded receptor-like proteins with amino acid sequences very similar to that of FPR.

[19] Mice have no less than 7 FPR receptors encoded by 7 genes that localize to chromosome 17A3.2 in the following order: Fpr1, Fpr-rs2 (or fpr2), Fpr-rs1 (or LXA4R), Fpr-rs4, Fpr-rs7, Fpr-rs7, Fpr-rs6, and Fpr-rs3; this locus also contains Pseudogenes ψFpr-rs2 and ψFpr-rs3 (or ψFpr-rs5) which lie just after Fpr-rs2 and Fpr-rs1, respectively.

[39][40] The following is a list of FPR2/ALX ligands and in parentheses their suggested pro-inflammatory or anti-inflammatory actions base on in vitro and animal model studies: a) bacterial and mitochondrial N-formyl peptides such as FMLP (pro-inflammatory but perhaps less significant or insignificant compared to the actions of LXA4, ATL, and RvD1 on FPR2); b) Hp(2-20), a non-formyl peptide derived from Helicobacter pylori (pro-inflammatory by promoting inflammatory responses against this stomach ulcer-causing pathogen); c) T21/DP107 and N36, which are N-acetylated polypeptides derived from the gp41 envelope protein of the HIV-1 virus, F peptide, which is derived from gp120 protein of the HIV-1 Bru strain virus, and V3 peptide, which is derived from a linear sequence of the V3 region of the HIV-1 MN strain virus (unknown effect on inflammation and HIV infection); d) the N-terminally truncated form of the chemotactic chemokine, CCL23, termed CCL23 splice variant CCL23β(amino acids 22–137) and SHAAGtide, which is a product of CCL23β cleavage by pro-inflammatory proteases (pro-inflammatory); e) two N-acetyl peptides, Ac2–26 and Ac9–25 of Annexin A1 (ANXA1 or lipocortin 1), which at high concentrations fully stimulate neutrophil functions but at lower concentrations leave neutrophils desensitized (i.e. unresponsive) to the chemokine IL-8 (CXCL8) (pro-inflammatory and anti-inflammatory, respectively, highlighting the duality of FPR2/ALX functions in inflammation); f) Amyloid beta(1–42) fragment and prion protein fragment PrP(106–126) (pro-inflammatory, suggesting a role for FPR2/ALX in the inflammatory components of diverse amyloid-based diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, prion-based diseases such as Transmissible spongiform encephalopathy, Creutzfeldt–Jakob disease, and Kuru), and numerous other neurological and non-neurological diseases [see amyloid]); g) the neuroprotective peptide, Humanin (anti-inflammatory by inhibiting the pro-inflammatory effects of Amalyoid beta(1-42) in promoting Alzheimer's disease-related inflammation); h) two cleaved soluble fragments of UPARAP which is the Urokinase-type plasminogen activator receptor (uPAR), D2D3(88–274) and uPAR(84–95) (pro-inflammatory); i) LL-37 and CRAMP, which are enzymatic cleavage products of human and rat, respectively, Cathelicidin-related antimicrobial peptides, numerous Pleurocidins which are a family of cationic antimicrobial peptides found in fish and other vertebrates structurally and functionally similar to cathelicidins,[29] and Temporin A, which is a frog-derived antimicrobial peptide ((pro-inflammatory products derived from host anti-microbial proteins); and j) Pituitary adenylate cyclase-activating polypeptide 27 (pro-inflammatory).

[17][41] This article incorporates text from the United States National Library of Medicine, which is in the public domain.