FPR2 Membrane Protein Introduction

Introduction of FPR2

FPR2, also referred to formyl peptide receptor 2, formyl peptide receptor-like 1 (FPRL1), FMLP-related receptor I (FMLP-R-I), lipoxin A4 receptor (LXA4 receptor, LXA4R), ALX or HM63, is a seven transmembrane G protein-coupled receptor that belongs to the formyl peptide receptor family, involved in antibacterial host defense and inflammatory activity. It is a 38.9 kDa protein of 351 amino acids and encoded by the gene mapping at the chromosome 19q13.41. FPR2 is a low-affinity receptor for N-formyl-methionyl peptides, which are a type of robust neutrophils chemotactic factors. This protein is located on the surface of cell types of many animal species and its associated pathways include the Akt signaling and innate immune system.

Basic Information of FPR2
Protein Name N-formyl peptide receptor 2
Gene Name FPR2
Organism Homo sapiens (Human)
UniProt ID P25090
Transmembrane Times 7
Length (aa) 351

Function of FPR2 Membrane Protein

FPR2 as a receptor is believed to play a critical role in detecting bacteria and modulating immune responses. In humans, it is expressed by diverse cell types of animal species, including fibroblasts, epithelial cells, endothelial cells, neuronal cells as well as most if not all immune cells. Initially, this receptor is recognized as a pattern recognition receptor detecting bacterial microorganisms via chemotactic formylated peptides and elicits pro-inflammatory responses. FPR2 is utilized by viruses for their own profit. For example, Annexin A1, one of FPR2 ligands, is merged in the budding virus membrane of the influenza A. Therefore, once influenza A viruses infect host cells, FPR2 will be activated. FPR2-signaling results in an increase in viral replication, a dysregulation of host immune responses and severe diseases. Except that, FPR2 can be activated by binding other kinds of ligands, such as lipoxin A4, resolvin D1 and so on.

Model of how FPR2 promotes harmful inflammation in a time scale manner.Fig.1 Model of how FPR2 promotes harmful inflammation in a time scale manner. (Alessi, 2017)

Application of FPR2 Membrane Protein in Literature

  1. Rahman F., et al. The annexin A1 receptor FPR2 regulates the endosomal export of influenza virus. Int J Mol Sci. 2018, 19(5). PubMed ID: 29738458

    The article showed that FPR2 signaling interferes with the endosomal trafficking of influenza viruses. It is the first time to raise a concept that monoclonal antibodies (McAbs) directed against FPR2 limit virus replications. This study finally suggested that the employment of anti-FPR2 antibody against influenza has a great prospect in the future application.

  2. Ampomah P. B., et al. Formyl peptide receptor 2 is regulated by RNA mimics and viruses through an IFN-β-STAT3-dependent pathway. FASEB J. 2018, 32(3): 1468-1478. PubMed ID: 29127186

    This study offers a novel insight into how RNA viruses possibly hijack the immune system to promote their replication and survival. Validation of regulatory elements might be useful in planning therapeutics for inflammatory diseases that are correlated with increased levels of FPR2. FPR2 is regulated by RNA mimics and viruses by the IFN-β-STAT3-dependent pathway.

  3. Wang C. S., et al. The G-protein-coupled receptor ALX/Fpr2 regulates adaptive Immune responses in mouse submandibular glands. Am J Pathol. 2018, 188(7): 1555-1562. PubMed ID: 29684359

    The results demonstrated that aging female knockout mice lacking ALX/Fpr2 (ALX homeobox protein (ALX)/N-formyl peptide receptor (FPR)-2) indicate a remarkable reduction in saliva flow rates and weight loss, an upregulation of autoantibody production, an increased level of autoimmune-related genes and CD20-positive B-cell population.

  4. De Buck M., et al. COOH-terminal SAA1 peptides fail to induce chemokines but synergize with CXCL8 and CCL3 to recruit leukocytes via FPR2. Blood. 2018, 131(4): 439-449. PubMed ID: 29371208

    SAA1 (Serum amyloid A1) desensitizes synergistic effects between intact SAA1α and CXCL8 in neutrophil chemotaxis, which suggests this peptide is able to bind formyl peptide receptor 2 (FPR2). This is proved by a complete blockade of synergy among the COOH-terminal SAA1 fragments and CXCL8 or CCL3 in monocyte and neutrophil chemotaxis, respectively, through the FPR2 antagonist WRW4.

  5. Lappas M., et al. Formyl peptide receptor-2 is decreased in foetal growth restriction and contributes to placental dysfunctionMol Hum Reprod. 2018, 24(2): 94-109. PubMed ID: 29272530

    Decreased FPR2 placental expression in idiopathic FGR leads to greatly altered trophoblast differentiation and endothelial functions in vitro. It is the first time to link placental FPR2 level with changes in the trophoblast and endothelial function that is likely to explain the placental insufficiency detected in FGR.

FPR2 Preparation Options

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  1. Alessi M C, et al. (2017). FPR2: A novel promising target for the treatment of Influenza. Front Microbiol. 8, 1719.

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