FPR1 (formyl peptide receptor 1)

2012-06-01   Jian Huang , Ji Ming Wang 





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.
Atlas Image
This gene is located in formylpeptide receptor gene cluster region including FPR1, FPR2 and FPR3 on chromosome 19p.


Size: 6127 bases.


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.


No known pseudogenes.



FPR1 gene encodes a putative 350 aminoacid protein with seven transmembrane segments, three extra- and two intra-cellular loops.
Atlas Image
Predicted transmembrane disposition of the human FPR1.


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 (=).


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.


Cell membrane.


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.


In primates, the sequence of FPR1 is highly conserved. Rabbit and mouse FPR1 share 78 and 76% identity with human FPR1 respectively.



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.
Atlas Image
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 name
Promoting glioblastoma progression.
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.
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.
Atlas Image
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 name
Mediating neutrophil accumulation at the sites of injury.
Entity name
Antibacteria host defense
Mediating host resistance against Listeria infection.


Pubmed IDLast YearTitleAuthors
95069201998Broad immunocytochemical localization of the formylpeptide receptor in human organs, tissues, and cells.Becker EL et al
21612131990Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA.Boulay F et al
99899801999Impaired antibacterial host defense in mice lacking the N-formylpeptide receptor.Gao JL et al
110859332000A 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 et al
112386592001Differential roles of the NPXXY motif in formyl peptide receptor signaling.He R et al
184339882008Receptor "hijacking" by malignant glioma cells: a tactic for tumor progression.Huang J et al
175751602007Transactivation of the epidermal growth factor receptor by formylpeptide receptor exacerbates the malignant behavior of human glioblastoma cells.Huang J et al
124014072002Formyl-peptide receptors revisited.Le Y et al
95531011998Identification of a ligand binding site in the human neutrophil formyl peptide receptor using a site-specific fluorescent photoaffinity label and mass spectrometry.Mills JS et al
78363711995Phosphorylation of the N-formyl peptide receptor carboxyl terminus by the G protein-coupled receptor kinase, GRK2.Prossnitz ER et al
92995161997Identification of an N-formyl peptide receptor ligand binding domain by a gain-of-function approach.Quehenberger O et al
115597062001Defective Gi protein coupling in two formyl peptide receptor mutants associated with localized juvenile periodontitis.Seifert R et al
194980852009International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family.Ye RD et al
159283032005Formylpeptide receptor FPR and the rapid growth of malignant human gliomas.Zhou Y et al

Other Information

Locus ID:

NCBI: 2357
MIM: 136537
HGNC: 3826
Ensembl: ENSG00000171051


dbSNP: 2357
ClinVar: 2357
TCGA: ENSG00000171051


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Neuroactive ligand-receptor interactionKEGGko04080
Neuroactive ligand-receptor interactionKEGGhsa04080
Staphylococcus aureus infectionKEGGko05150
Staphylococcus aureus infectionKEGGhsa05150
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR ligand bindingREACTOMER-HSA-500792
Class A/1 (Rhodopsin-like receptors)REACTOMER-HSA-373076
Peptide ligand-binding receptorsREACTOMER-HSA-375276
Formyl peptide receptors bind formyl peptides and many other ligandsREACTOMER-HSA-444473
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (i) signalling eventsREACTOMER-HSA-418594
Neutrophil degranulationREACTOMER-HSA-6798695
Interleukin-10 signalingREACTOMER-HSA-6783783

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
265162012015Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1.95
166754462006Annexin I regulates SKCO-15 cell invasion by signaling through formyl peptide receptors.56
180563532007Formyl peptide receptor-1 activation enhances intestinal epithelial cell restitution through phosphatidylinositol 3-kinase-dependent activation of Rac1 and Cdc42.49
151871492004An annexin 1 N-terminal peptide activates leukocytes by triggering different members of the formyl peptide receptor family.44
219210272011Enteric commensal bacteria induce extracellular signal-regulated kinase pathway signaling via formyl peptide receptor-dependent redox modulation of dual specific phosphatase 3.40
159283032005Formylpeptide receptor FPR and the rapid growth of malignant human gliomas.36
209301152011Annexin-1 signals mitogen-stimulated breast tumor cell proliferation by activation of the formyl peptide receptors (FPRs) 1 and 2.36
202374962010New genetic associations detected in a host response study to hepatitis B vaccine.27
156614002005Human platelets exhibit chemotaxis using functional N-formyl peptide receptors.26
158668652005Cross-talk between fMLP and vitronectin receptors triggered by urokinase receptor-derived SRSRY peptide.26


Jian Huang ; Ji Ming Wang

FPR1 (formyl peptide receptor 1)

Atlas Genet Cytogenet Oncol Haematol. 2012-06-01

Online version: http://atlasgeneticsoncology.org/gene/44328/fpr1