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FPR3

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Target not currently curated in GtoImmuPdb

Target id: 224

Nomenclature: FPR3

Family: Formylpeptide receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 353 19q13.41 FPR3 formyl peptide receptor 3 1,14
Mouse 7 351 17 A3.2 Fpr3 formyl peptide receptor 3 7
Rat 7 - 1 Fpr3 formyl peptide receptor 3 13
Previous and Unofficial Names Click here for help
FMLPY | FPRH1 | FPRL2 | Fprl1 | Lxa4r | LXA4-R
Database Links Click here for help
Specialist databases
GPCRdb fpr3_human (Hs), fprs1_mouse (Mm)
Other databases
Alphafold P25089 (Hs), O08790 (Mm)
ChEMBL Target CHEMBL3407315 (Mm)
Ensembl Gene ENSG00000187474 (Hs), ENSMUSG00000079700 (Mm), ENSRNOG00000031331 (Rn)
Entrez Gene 2359 (Hs), 14294 (Mm), 292413 (Rn)
Human Protein Atlas ENSG00000187474 (Hs)
KEGG Gene hsa:2359 (Hs), mmu:14294 (Mm), rno:292413 (Rn)
OMIM 136539 (Hs)
Pharos P25089 (Hs)
RefSeq Nucleotide NM_002030 (Hs), NM_008042 (Mm)
RefSeq Protein NP_002021 (Hs), NP_032068 (Mm)
UniProtKB P25089 (Hs), O08790 (Mm)
Wikipedia FPR3 (Hs)
Natural/Endogenous Ligands Click here for help
annexin I-(2-26) {Sp: Human}
F2L {Sp: Human} , F2L {Sp: Mouse, Rat}
humanin {Sp: Human}

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LXA4 Small molecule or natural product Mm Full agonist 8.8 pKd 18
⤷ pKd 8.8 [18]
F2L-[125I]Tyr Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 8.0 pKd 12
⤷ pKd 8.0 [12]
humanin {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.9 pEC50 9
⤷ pEC50 8.9 [9]
WKYMVm Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 8.5 pEC50 4
⤷ pEC50 8.5 (EC50 3x10-9 M) [4]
F2L {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 8.0 – 8.2 pEC50 12
⤷ pEC50 8.0 – 8.2 [12]
fMet-Met-Tyr-Ala-Leu-Phe Peptide Click here for species-specific activity table Hs Full agonist 6.0 pEC50 15
⤷ pEC50 6.0 (EC50 1x10-6 M) [15]
annexin I-(2-26) {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 5.0 – 7.0 pEC50 6
⤷ pEC50 5.0 – 7.0 [6]
Hp(2-20) Peptide Click here for species-specific activity table Hs Full agonist 5.0 pEC50 2
⤷ pEC50 5.0 [2]
View species-specific agonist tables
Agonist Comments
1) Humanin and formyl-humanin stimulate chemotaxis of transfected CHO cells that individually express FPR3 and FPR2/ALX.
2) F2L is an N-terminal acetylated cleavage production of heme-binding protein, an intracellular tetrapyrolle-binding protein. The peptide may be released by apoptotic and necrotic cells.
3) The agonistic activity of WKYMVM and WKYMVm at FPR3 is non-selective since the peptides also activate FPR2/ALX and FPR1 and with higher potency.
4) Hp(2-20) activates both FPR2/ALX and FPR3, with a higher potency on FPR2/ALX.
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
WRWWWW Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.0 pIC50 17
⤷ pIC50 6.0 [17]
Antagonist Comments
WKWWWW has better selectivity for FPR2/ALX.
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Phospholipase A2 stimulation
References: 
Secondary Transduction Mechanisms Click here for help
Comments:  FPR3 has not been extensively studied for its activation of secondary signaling mediators.
References: 
Tissue Distribution Click here for help
The human FPR3 is primarily a receptor of monocytes, macrophages and dendritic cells. It is not expressed in human neutrophils. The mouse fpr-rs2 gene production (mouse FPR2), is expressed in neutrophils. Although FPR3 is found in human monocytes, studies have shown that approximately one third of the individuals tested lack cell surface expression of this receptor. In a subsequent study, FPR3 was found in small intracellular vesicles in transfected HEK 293 cells (Rabiet et al., 2011). A structural determinant, localized in the extracellular domains of FPR3 is considered responsible for the intracellular localization. Likewise, exogenous expression of mouse Fpr3 resulted in an intracellular localization in transfected RBL-2H3, HeLa and HEK 293 cells (Migeotte et al., 2006). However, Wang et al. reported successful cell surface expression of FPR3 in stably transfected HEK 293S cells.
Species:  Human
Technique:  Immunocytochemistry
References:  10-12,16,19-20
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Similar to those described in FPR1 information sheet. FPR3-mediated activation of leukocytes has been studied mostly in chemotaxis and calcium mobilization assays.
Species:  Human
Tissue:  Monocytes, transfected cells
Response measured:  Chemotaxis, calcium mobilization
References:  12,16,20
Physiological Functions Click here for help
FPR3 is primarily expressed in monocytes, macrophages and dendritic cells. Its functions other than directing cell migration remain to be characterized.
Species:  Human
Tissue:  Monocytes, macrophages and dendritic cells
References:  11-12,20
Physiological Consequences of Altering Gene Expression Click here for help
A Fpr3-specific knockout line has not been reported. A recent study showed that genetic deletion of mouse fpr-rs2, which encodes a receptor (mouse FPR2) with properties of human FPR2/ALX, leads to diminished responsiveness to F2L (Gao et al., 2007) . This finding indicates that the mouse FPR2 has functional properties similar to human FPR3, even though F2L is highly selective for human FPR3. In another recent study, mice lacking both Fpr2 and Fpr3 (Dufton et al., 2010) showed exacerbated vascular inflammation after ischemia reperfusion injury of the mesenteric artery. Exogenous delivery of LXA4 was unable to reduce the inflammatory response in the Fpr2/Fpr3 double KO mice, but had an anti-inflammatory effect in WT mice (Brancaleone et al., 2013).
Species:  Mouse
Tissue:  Mesenteric artery, monocytes
Technique:  Gene targeting in embryonic stem cells
References:  3,5,8

References

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1. Bao L, Gerard NP, Eddy RL Jr, Shows TB, Gerard C. (1992) Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19. Genomics, 13: 437-440. [PMID:1612600]

2. Betten A, Bylund J, Christophe T, Cristophe T, Boulay F, Romero A, Hellstrand K, Dahlgren C. (2001) A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis. J Clin Invest, 108 (8): 1221-8. [PMID:11602630]

3. Brancaleone V, Gobbetti T, Cenac N, le Faouder P, Colom B, Flower RJ, Vergnolle N, Nourshargh S, Perretti M. (2013) A vasculo-protective circuit centered on lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 operative in murine microcirculation. Blood, 122 (4): 608-17. [PMID:23733341]

4. Christophe T, Karlsson A, Dugave C, Rabiet MJ, Boulay F, Dahlgren C. (2001) The synthetic peptide Trp-Lys-Tyr-Met-Val-Met-NH2 specifically activates neutrophils through FPRL1/lipoxin A4 receptors and is an agonist for the orphan monocyte-expressed chemoattractant receptor FPRL2. J Biol Chem, 276 (24): 21585-93. [PMID:11285256]

5. Dufton N, Hannon R, Brancaleone V, Dalli J, Patel HB, Gray M, D'Acquisto F, Buckingham JC, Perretti M, Flower RJ. (2010) Anti-inflammatory role of the murine formyl-peptide receptor 2: ligand-specific effects on leukocyte responses and experimental inflammation. J Immunol, 184 (5): 2611-9. [PMID:20107188]

6. Ernst S, Lange C, Wilbers A, Goebeler V, Gerke V, Rescher U. (2004) An annexin 1 N-terminal peptide activates leukocytes by triggering different members of the formyl peptide receptor family. J Immunol, 172 (12): 7669-76. [PMID:15187149]

7. Gao JL, Chen H, Filie JD, Kozak CA, Murphy PM. (1998) Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse. Genomics, 51 (2): 270-6. [PMID:9722950]

8. Gao JL, Guillabert A, Hu J, Le Y, Urizar E, Seligman E, Fang KJ, Yuan X, Imbault V, Communi D et al.. (2007) F2L, a peptide derived from heme-binding protein, chemoattracts mouse neutrophils by specifically activating Fpr2, the low-affinity N-formylpeptide receptor. J Immunol, 178 (3): 1450-6. [PMID:17237393]

9. Harada M, Habata Y, Hosoya M, Nishi K, Fujii R, Kobayashi M, Hinuma S. (2004) N-Formylated humanin activates both formyl peptide receptor-like 1 and 2. Biochem Biophys Res Commun, 324 (1): 255-61. [PMID:15465011]

10. He HQ, Liao D, Wang ZG, Wang ZL, Zhou HC, Wang MW, Ye RD. (2013) Functional characterization of three mouse formyl peptide receptors. Mol Pharmacol, 83 (2): 389-98. [PMID:23160941]

11. Migeotte I, Communi D, Parmentier M. (2006) Formyl peptide receptors: a promiscuous subfamily of G protein-coupled receptors controlling immune responses. Cytokine Growth Factor Rev, 17 (6): 501-19. [PMID:17084101]

12. Migeotte I, Riboldi E, Franssen JD, Grégoire F, Loison C, Wittamer V, Detheux M, Robberecht P, Costagliola S, Vassart G et al.. (2005) Identification and characterization of an endogenous chemotactic ligand specific for FPRL2. J Exp Med, 201 (1): 83-93. [PMID:15623572]

13. Morley AD, King S, Roberts B, Lever S, Teobald B, Fisher A, Cook T, Parker B, Wenlock M, Phillips C et al.. (2012) Lead optimisation of pyrazoles as novel FPR1 antagonists. Bioorg Med Chem Lett, 22 (1): 532-6. [PMID:22094028]

14. Murphy PM, Ozçelik T, Kenney RT, Tiffany HL, McDermott D, Francke U. (1992) A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family. J Biol Chem, 267 (11): 7637-43. [PMID:1373134]

15. Rabiet MJ, Huet E, Boulay F. (2005) Human mitochondria-derived N-formylated peptides are novel agonists equally active on FPR and FPRL1, while Listeria monocytogenes-derived peptides preferentially activate FPR. Eur J Immunol, 35 (8): 2486-95. [PMID:16025565]

16. Rabiet MJ, Macari L, Dahlgren C, Boulay F. (2011) N-formyl peptide receptor 3 (FPR3) departs from the homologous FPR2/ALX receptor with regard to the major processes governing chemoattractant receptor regulation, expression at the cell surface, and phosphorylation. J Biol Chem, 286 (30): 26718-31. [PMID:21543323]

17. Shin EH, Lee HY, Kim SD, Jo SH, Kim MK, Park KS, Lee H, Bae YS. (2006) Trp-Arg-Trp-Trp-Trp-Trp antagonizes formyl peptide receptor like 2-mediated signaling. Biochem Biophys Res Commun, 341 (4): 1317-22. [PMID:16476585]

18. Takano T, Fiore S, Maddox JF, Brady HR, Petasis NA, Serhan CN. (1997) Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Exp Med, 185 (9): 1693-704. [PMID:9151906]

19. Wang X, Zhang S. (2011) Production of a bioengineered G-protein coupled receptor of human formyl peptide receptor 3. PLoS ONE, 6 (8): e23076. [PMID:21853070]

20. Yang D, Chen Q, Gertz B, He R, Phulsuksombati M, Ye RD, Oppenheim JJ. (2002) Human dendritic cells express functional formyl peptide receptor-like-2 (FPRL2) throughout maturation. J Leukoc Biol, 72 (3): 598-607. [PMID:12223529]

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