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Gene and Protein Information | ||||||
class A G protein-coupled receptor | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 7 | 350 | 19q13.41 | FPR1 | formyl peptide receptor 1 | 4,58 |
Mouse | 7 | 364 | 17 10.63 cM | Fpr1 | formyl peptide receptor 1 | 24 |
Rat | 7 | 355 | 1q12 | Fpr1 | formyl peptide receptor 1 | 56 |
Previous and Unofficial Names |
NFPR | FPR | formyl peptide receptor 1 | fMLF-R |
Database Links | |
Specialist databases | |
GPCRdb | fpr1_human (Hs), fpr1_mouse (Mm) |
Other databases | |
Alphafold | P21462 (Hs), P33766 (Mm) |
ChEMBL Target | CHEMBL3359 (Hs), CHEMBL1770037 (Mm) |
Ensembl Gene | ENSG00000171051 (Hs), ENSMUSG00000045551 (Mm), ENSRNOG00000011174 (Rn) |
Entrez Gene | 2357 (Hs), 14293 (Mm), 292409 (Rn) |
Human Protein Atlas | ENSG00000171051 (Hs) |
KEGG Gene | hsa:2357 (Hs), mmu:14293 (Mm), rno:292409 (Rn) |
OMIM | 136537 (Hs) |
Pharos | P21462 (Hs) |
RefSeq Nucleotide | NM_002029 (Hs), NM_013521 (Mm), NM_001106216 (Rn) |
RefSeq Protein | NP_002020 (Hs), NP_038549 (Mm), NP_001099686 (Rn) |
UniProtKB | P21462 (Hs), P33766 (Mm) |
Wikipedia | FPR1 (Hs) |
Natural/Endogenous Ligands |
annexin I {Sp: Human} , annexin I {Sp: Mouse} , annexin I {Sp: Rat} |
cathepsin G {Sp: Human} , cathepsin G {Sp: Mouse} , cathepsin G {Sp: Rat} |
spinorphin |
Potency order of endogenous ligands (Human) |
fMet-Leu-Phe > cathepsin G (CTSG, P08311) > annexin I (ANXA1, P04083) [46,81] |
Download all structure-activity data for this target as a CSV file
Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
FPR1-mediated neutrophil functions have different requirements for agonist concentrations, from low (chemotaxis) to high (superoxide generation). Some early studies of fMet-Leu-Phe were conducted on rabbit neutrophils [10,24]. The annexin I peptides include Ac2-12, Ac2-26 and Ac9-25. These peptides bind to both FPR1 and FPR2 with similar affinities, and therefore non-selective according to IUPHAR standard [18,27,37,84]. T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of FPR1 [80]. AG-14 (1,3-benzodioxolane-5-carboxylic acid 4`-benzyloxy-3`-methoxybenzylidene-hydrazide) represents a novel small-molecule agonist of FPR1. Selected chiral compounds are potent mixed FPR1/FPR2 agonists, among which R-(-)-forms generally exhibits higher activity than the S-(+)-enantiomers [16]. Benzimidazole derivatives include 2-(benzimidazol-2-ylthio)-N-phenylacetamide-derivatives and 2-(5-alkoxybenzimidazol-2-ylthio)-N-phenylacetamide derivatives, among which FPR1-specific agonists are AG-09/1, AG-09/2, AG-09/13, AG-09/18, AG-09/19, AG-09/21, AG-11/03, AG-11/05 and AG-11/23, while the other compounds tested in the series are mixed FPR1/FPR2 agonists or FPR2-specific agonists [38-39]. Despite acting as a calcium-mobilizing agonist at mouse Fpr1, spinorphin is a weak chemotactic agonist and effectively blocks neutrophil chemotaxis induced by fMLF at concentrations selective for mouse Fpr1 [48]. |
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CHIPS is a 14.1 kDa protein found in more than half of the clinical strains of Staphylococcus aureus. Its N-terminal peptides of various lengths are also FPR1 antagonists but are 3 orders of magnitude less potent [30]. Boc-Met-Leu-Phe is also termed Boc1, and Boc-Phe-Leu-Phe-Leu-Phe is referred to as Boc2. The latter is an antagonist of both FPR1 and FPR2, and therefore is considered non-selective. Spinorphin is an endogenous peptide with the sequence of Leu-Val-Val-Tyr-Pro-Trp-Thr. BVT173187 (3,5-dichloro-N-(2-chloro-5-methyl-phenyl)-2-hydroxy-benzamide) fulfills the criteria for an FPR1 inhibitor selective for FPR1 over FPR2, and the potency is the same as that of cyclosporine H, but signaling through C5aR and CXCR (recognizing IL8) is also affected by BVT173187. |
Immunopharmacology Comments |
The primary function of FPR1 is recognition of formylpeptides. Detection of bacterial N-formylpeptides via FPR1 activates immune-cell chemotaxis and cytokine release, making this GPCR an important component of the host defense mechanism. Osei-Owusu et al. (2019) demonstrated that FPR1 on immune cells is the target of the needle cap protein (LcrV; Uniprot accession P0C7U7) of Yersinia pestis (the plague bacterium), via which the bacteria destroy host immune cells [61]. By eliminating host cellular defences Y. pestis creates a more hospitable environment in which it can survive and reproduce. In the same study, the team also identified a candidate resistance mutation in human FPR1 that provides neutrophils with some protection from Y. pestis-induced destruction. |
Cell Type Associations | ||||||||
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Immuno Process Associations | ||
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Primary Transduction Mechanisms | |
Transducer | Effector/Response |
Gi/Go family |
Adenylyl cyclase inhibition Phospholipase C stimulation Phospholipase A2 stimulation Phospholipase D stimulation |
References: 1,28,57,76 |
Secondary Transduction Mechanisms | |
Transducer | Effector/Response |
Calcium channel | |
Comments: Increase of intracellular Ca2+ level results in opening of membrane Ca2+ channel in fMLF-stimulated cells. This response is secondary to release of Ca2+ from intracelluar stores. | |
References: 50,59,64,67 |
Tissue Distribution | ||||||||
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Expression Datasets | |
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Physiological Consequences of Altering Gene Expression | ||||||||||
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Phenotypes, Alleles and Disease Models | Mouse data from MGI | ||||||||||||||||||||||||||||||
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Biologically Significant Variants | ||||||||||
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