Nomenclature: FPR3

Family: Formylpeptide receptors

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing. 

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 353 19q13.3-q13.4 FPR3 formyl peptide receptor 3 1,14
Mouse 7 351 17 Fpr3 formyl peptide receptor 3 7
Rat 7 410 1 Fpr3 formyl peptide receptor 3 13
Previous and Unofficial Names
FMLPY
RMLP-R-I
FPRH1
FPRL2
formyl peptide receptor-like 2
LOC292413
RGD1566044
RGD1566044_predicted
formyl peptide receptor 3
similar to N-formylpeptide receptor-like 2
similar to N-formylpeptide receptor-like 2 (predicted)
Lxa4r
LXA4-R
Fprl1
Fpr-rs1
Database Links
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
F2L {Sp: Human}
humanin {Sp: Human}
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
LXA4 Mm Full agonist 8.82 pKd 18
pKd 8.82 [18]
F2L-[125I]Tyr Hs Full agonist 8.0 pKd 12
pKd 8.0 [12]
humanin {Sp: Human} Hs Full agonist 8.95 pEC50 9
pEC50 8.95 [9]
WKYMVm Hs Full agonist 8.52 pEC50 4
pEC50 8.52 (EC50 3x10-9 M) [4]
F2L {Sp: Human} Hs Full agonist 8.0 – 8.2 pEC50 12
pEC50 8.0 – 8.2 [12]
fMet-Met-Tyr-Ala-Leu-Phe Hs Full agonist 6.0 pEC50 15
pEC50 6.0 (EC50 1x10-6 M) [15]
annexin I-(2-26) {Sp: Human} Hs Full agonist 5.0 – 7.0 pEC50 6
pEC50 5.0 – 7.0 [6]
Hp(2-20) 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 Affinity Units Reference
WRWWWW Hs Antagonist 6.0 pIC50 17
pIC50 6.0 [17]
Antagonist Comments
WKWWWW has better selectivity for FPR2/ALX.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Phospholipase A2 stimulation
References: 
Secondary Transduction Mechanisms
Comments:  FPR3 has not been extensively studied for its activation of secondary signaling mediators.
References: 
Tissue Distribution
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

Show »

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
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
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
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

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. Genomics13: 437-440. [PMID:1612600]

2. Betten A, Bylund J, Christophe 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 Invest108: 1221-1228. [PMID:11602630]

3. Brancaleone V, Gobbetti T, Cenac N, le Faoudier P, Colom B, Flower RJ, Vergnolle N, Nourshargh S, Perretti M. (2013) A vasculo-protective circuit centred on Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 operative in murine microcirculation. Blood,  [Epub ahead of print]. [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 Chem276: 21585-21593. [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 Immunology172: 7669-7676. [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. Genomics51: 270-276. [PMID:9722950]

8. Gao JL, Guillabert A, Hu J, Le Y, Urizar E, Seligman E, Fang KJ, Yuan X, Imbault V, Communi D, Wang JM, Parmentier M, Murphy PM, Migeotte I. (2007) F2L, a peptide derived from heme-binding protein, chemoattracts mouse neutrophils by specifically activating Fpr2, the low-affinity N-formylpeptide receptor. J Immunology178: 1450-1456. [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 Commun324: 255-261. [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 Rev17: 501-519. [PMID:17084101]

12. Migeotte I, Riboldi E, Franssen JD, Grégoire F, Loison C, Wittamer V, Detheux M, Robberecht P, Costagliola S, Vassart G, Sozzani S, Parmentier M, Communi D. (2005) Identification and characterization of an endogenous chemotactic ligand specific for FPRL2. J Exp Med201: 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, Ozcelik 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: 7637-7643. [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 Immunol35: 2486-2495. [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. (2004) Trp-Arg-Trp-Trp-Trp-Trp antagonizes formyl peptide receptor like 2-mediated signaling. Biochem Biophys Res Commun341: 1317-1322. [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: 1693-1704. [PMID:9151906]

19. Wang X, Zhang S. (2011) Production of a bioengineered G-protein coupled receptor of human formyl peptide receptor 3. PLoS ONE6 (8): e23076. [PMID:21853070]

20. Yang D, Chen Q He R, Phulsuksombati M, Ye RD, Oppenheim JJ. (2002) Human dendritic cells express functional formyl peptide receptor-like-2 (FPRL2) throughout maturation. J Leukoc Biol72: 598-607. [PMID:12223529]

To cite this database page, please use the following:

Formylpeptide receptors: FPR3. Last modified on 19/12/2013. Accessed on 25/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=224.

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