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FPR1 (formyl peptide receptor 1)

Written2012-06Jian Huang, Ji Ming Wang
High Altitude Military Medical College, Third Military Medical University, Chongqing, 400038, China (JH); Laboratory of Molecular Immunoregulation, Cancer, inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA (JMW)

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Other aliasFMLP
LocusID (NCBI) 2357
Atlas_Id 44328
Location 19q13.41  [Link to chromosome band 19q13]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


Note FPR1 is a G protein-coupled receptor (GPCR), originally identified in phagocytic leukocytes, which mediates cell chemotaxis and activation in response to the bacterial chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF).
A number of host-derived chemotactic agonists of FPR1 have been identified, including formyl peptides potentially released by mitochondria of ruptured cells, Annexin I produced by activated epithelia, and a neutrophil granule protein, cathepsin G. In addition, functional FPR1 has been detected in cells of nonhematopoietic origin, such as lung epithelial cells and hepatocytes. These findings suggest that FPR1 is involved in a broader spectrum of pathophysiologic processes.
  This gene is located in formylpeptide receptor gene cluster region including FPR1, FPR2 and FPR3 on chromosome 19p.
Description Size: 6127 bases.
Transcription All three genes, FPR1, FPR2 and FPR3, are clustered on chromosome 19q13.3. FPR1 is encoded by a 6 kb single copy gene. The open reading frame is intronless but the 5' untranslated region resides in three exons. The start sites for transcription and translation are separated by approximately 5 kb. The FPR1 gene contains three Alu repeats, one in each intron and a third in the 3' flanking region. The proposed promoter contains a nonconsensus TATA box and an inverted CCAAT element.
Pseudogene No known pseudogenes.


Note FPR1 gene encodes a putative 350 aminoacid protein with seven transmembrane segments, three extra- and two intra-cellular loops.
  Predicted transmembrane disposition of the human FPR1.
Description The protein sequence of the FPR-98 isoform (Leu110, Ala346) is shown (Boulay et al.,1990; Ye et al., 2009). The transmembrane domains (TMs) are predicted based on hydrophobicity of the amino acid sequence and on similarities to the rhodopsin structure. The amino acids that form the boundaries of the transmembrane domains are numbered. One-letter amino acid code is used. The square blocks in reverce color represent positions at which amino acid substitutions result from polymorphisms, including amino acids 11 (Ile/Thr), 47 (Val/Ala), 101 (Leu/Val), 190 (Arg/Trp), 192 (Asn/Lys) and 346 (Ala/Glu). The circle blocks in reverse color indicate amino acids with known functions as follows. Arg84, Lys85, and Asp284 are critical for high-affinity binding of fMLF (Mills et al., 1998; Quehenberger et al., 1997). Asp122, Arg123, and Cys124 are the signature sequence for G protein interaction (DRY in many GPCRs). NPMLY in the TM7 are known signature sequence (NPXXY) for receptor internalization (Gripentrog et al., 2000; He et al., 2001). The 11 Ser and Thr residues in the cytoplasmic tail are potential phosphorylation sites for GRK2 and GRK3 (Prossnitz et al., 1995). CHO, carbohydrate, marks the identified and potential (in parenthesis) sites for N-glycosylation. The predicted disulfide bond between Cys98 and Cys176 is marked with double-line (=).
Expression FPR1 has been detected in phagocytic leukocytes, hepatocytes, dendritic cells, astrocytes, microglia cells, and the tunica media of coronary arteries. Becker et al. showed that FPR1 or an antigenically similar receptor is located in a number of human tissues and organs, including secretory cells in the thyroid, adrenals and other glands, the liver, the central nervous system, and neurons in the autonomic nervous system. FPR1 is also expressed in neutrophils of non-human primates and rodents.
Localisation Cell membrane.
Function Agonist binding to FPR1 elicits a cascade of signal transduction pathways that involve phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinases (MAPK), and the transcription factors nuclear factor-κB and hypoxic inducible factor-1α (HIF-1α). Because of its expression in cells of the immune system and its interaction with bacterial chemotactic peptides, this receptor was thought to participate in host defense against microbial infection. In addition, FPR1 expressed in highly malignant human glioblastoma promotes tumor progression.
Homology In primates, the sequence of FPR1 is highly conserved. Rabbit and mouse FPR1 share 78 and 76% identity with human FPR1 respectively.


Note Two loss of funtion mutations (F110S and C126W) that correlate with localized juvenile periodontitis. The F110S mutation resides in the third transmembrane domain, whereas the C126W mutation resides in the second intracellular loop.
  Amino acid sequence of FPR-WT and localization of the F110S and C126W mutations (Seifert et al., 2001). Shown is the two-dimensional structure of FPR-WT (isoform 26) (27). Amino acids are given in one-letter code. The FPR N terminus (top) faces the extracellular space; the FPR C terminus (bottom) faces the cytosol. The transmembrane domains are included in the boxed area. Extracellular consensus sites for N-glycosylation are shown (Y). The positions of the F110S and C126W mutations are indicated (•). There is a disulfide bridge between the first and second extracellular loops. Note that the consensus sites for N-glycosylation are not altered in FPR-F110S and FPR-C126W.

Implicated in

Entity Glioblastoma
Note Promoting glioblastoma progression.
Prognosis FPR1 protein staining was detected in 11 of 14 grade III anaplastic astrocytoma specimens and six of six grade IV glioblastoma multiforme specimens. Microvessels and necrotic tumor cells were readily visible among FPR1-positive intact tumor cells. In contrast, only two of 13 less aggressive grade II astrocytoma specimens showed positive FPR staining. Thus, FPR expression appears to be associated with a majority of poorly differentiated primary human gliomas of grades III and IV.
Cytogenetics Highly malignant human glioblastoma and anaplastic astrocytoma specimens were stained positively for FPR1. FPR1 was expressed selectively in glioma cell lines with a more highly malignant phenotype. FPR expressed in glioblastoma cell lines mediates cell chemotaxis, proliferation and production of an angiogenic factor, vascular endothelial growth factor (VEGF), in response to agonists released by necrotic tumor cells. Furthermore, FPR in glioblastoma cells activates the receptor for epidermal growth factor (EGFR) by increasing the phosphorylation of a selected tyrosine residue in the intracellular tail of EGFR. Thus, FPR hijacked by human glioblastoma cells exploits the function of EGFR to promote rapid tumor progression.
The role of FPR in glioblastoma progression. FPR on glioblastoma cells is activated by agonists released by necrotic tumor cells. The signaling cascade coupled to FPR in tumor cells activates PI3 kinase, MAPKs, PLC, PLD, Akt/Bcl2 and transcription factors such as NFκB, STAT3 and HIF-1α, to enhance cell chemotaxis, growth and release of angiogenic factors. The FPR function in glioblastoma cells is partially mediated by EGFR through a Src-kinase dependent transactivation pathway (Huang et al., 2008).
Entity Inflammation
Note Mediating neutrophil accumulation at the sites of injury.
Entity Antibacteria host defense
Note Mediating host resistance against Listeria infection.


Broad immunocytochemical localization of the formylpeptide receptor in human organs, tissues, and cells.
Becker EL, Forouhar FA, Grunnet ML, Boulay F, Tardif M, Bormann BJ, Sodja D, Ye RD, Woska JR Jr, Murphy PM.
Cell Tissue Res. 1998 Apr;292(1):129-35.
PMID 9506920
Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA.
Boulay F, Tardif M, Brouchon L, Vignais P.
Biochem Biophys Res Commun. 1990 May 16;168(3):1103-9.
PMID 2161213
Impaired antibacterial host defense in mice lacking the N-formylpeptide receptor.
Gao JL, Lee EJ, Murphy PM.
J Exp Med. 1999 Feb 15;189(4):657-62.
PMID 9989980
A single amino acid substitution (N297A) in the conserved NPXXY sequence of the human N-formyl peptide receptor results in inhibition of desensitization and endocytosis, and a dose-dependent shift in p42/44 mitogen-activated protein kinase activation and chemotaxis.
Gripentrog JM, Jesaitis AJ, Miettinen HM.
Biochem J. 2000 Dec 1;352 Pt 2:399-407.
PMID 11085933
Differential roles of the NPXXY motif in formyl peptide receptor signaling.
He R, Browning DD, Ye RD.
J Immunol. 2001 Mar 15;166(6):4099-105.
PMID 11238659
Receptor "hijacking" by malignant glioma cells: a tactic for tumor progression.
Huang J, Chen K, Gong W, Zhou Y, Le Y, Bian X, Wang JM.
Cancer Lett. 2008 Aug 28;267(2):254-61. Epub 2008 Apr 22.
PMID 18433988
Transactivation of the epidermal growth factor receptor by formylpeptide receptor exacerbates the malignant behavior of human glioblastoma cells.
Huang J, Hu J, Bian X, Chen K, Gong W, Dunlop NM, Howard OM, Wang JM.
Cancer Res. 2007 Jun 15;67(12):5906-13.
PMID 17575160
Formyl-peptide receptors revisited.
Le Y, Murphy PM, Wang JM.
Trends Immunol. 2002 Nov;23(11):541-8.
PMID 12401407
Identification of a ligand binding site in the human neutrophil formyl peptide receptor using a site-specific fluorescent photoaffinity label and mass spectrometry.
Mills JS, Miettinen HM, Barnidge D, Vlases MJ, Wimer-Mackin S, Dratz EA, Sunner J, Jesaitis AJ.
J Biol Chem. 1998 Apr 24;273(17):10428-35.
PMID 9553101
Phosphorylation of the N-formyl peptide receptor carboxyl terminus by the G protein-coupled receptor kinase, GRK2.
Prossnitz ER, Kim CM, Benovic JL, Ye RD.
J Biol Chem. 1995 Jan 20;270(3):1130-7.
PMID 7836371
Identification of an N-formyl peptide receptor ligand binding domain by a gain-of-function approach.
Quehenberger O, Pan ZK, Prossnitz ER, Cavanagh SL, Cochrane CG, Ye RD.
Biochem Biophys Res Commun. 1997 Sep 18;238(2):377-81.
PMID 9299516
Defective Gi protein coupling in two formyl peptide receptor mutants associated with localized juvenile periodontitis.
Seifert R, Wenzel-Seifert K.
J Biol Chem. 2001 Nov 9;276(45):42043-9. Epub 2001 Sep 14.
PMID 11559706
International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family.
Ye RD, Boulay F, Wang JM, Dahlgren C, Gerard C, Parmentier M, Serhan CN, Murphy PM.
Pharmacol Rev. 2009 Jun;61(2):119-61. Epub 2009 Jun 4.
PMID 19498085
Formylpeptide receptor FPR and the rapid growth of malignant human gliomas.
Zhou Y, Bian X, Le Y, Gong W, Hu J, Zhang X, Wang L, Iribarren P, Salcedo R, Howard OM, Farrar W, Wang JM.
J Natl Cancer Inst. 2005 Jun 1;97(11):823-35.
PMID 15928303


This paper should be referenced as such :
Huang, J ; Wang, JM
FPR1 (formyl peptide receptor 1)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(12):889-893.
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External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)2357
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
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indexed on : Thu Oct 18 17:36:59 CEST 2018

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