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FPR2

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 223

Nomenclature: FPR2

Family: Formylpeptide receptors, Leukotriene receptors

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 7 351 19q13.41 FPR2 formyl peptide receptor 2 4,69
Mouse 7 351 17 A3.2 Fpr2 formyl peptide receptor 2 34,97
Rat 7 351 1q12 Fpr2 formyl peptide receptor 2 14,68
Previous and Unofficial Names Click here for help
ALXR | FMLPX | FPRH1 | LXA4R | ALX | FPRH2 | FPRL1 | RFP | formyl peptide receptor-like 1 | formyl peptide receptor 2 | formyl peptide receptor, related sequence 2 | Fpr-rs2 | ALX/FPR2 | FPR2A
Database Links Click here for help
Specialist databases
GPCRdb fpr2_human (Hs), fpr2_mouse (Mm)
Other databases
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
annexin I {Sp: Human} , annexin I {Sp: Mouse} , annexin I {Sp: Rat}
aspirin triggered lipoxin A4
aspirin-triggered resolvin D1
CRAMP {Sp: Mouse}
humanin {Sp: Human}
LL-37 {Sp: Human}
LXA4
PrP106-126
resolvin D1
serum amyloid A {Sp: Human}
Potency order of endogenous and other ligands
LXA4 = aspirin triggered lipoxin A4 = ATLa2 = resolvin D1 > LTC4 = LTD4 >> 15-deoxy-LXA4 >> fMet-Leu-Phe  [17,26,29,39,97]

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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
WKYMVm Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 10.1 pKd 15,43,45,58
pKd 10.1 [15,43,45,58]
[3H]LXA4 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 9.1 – 9.3 pKd 26,28
pKd 9.1 – 9.3 (Kd 7x10-10 – 5x10-10 M) [26,28]
LXA4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Partial agonist 8.8 – 9.3 pKd 26,28
pKd 8.8 – 9.3 [26,28]
[3H]LXA4 Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Full agonist 8.8 pKd 97
pKd 8.8 (Kd 1.5x10-9 M) [97]
[3H]LXA4 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Full agonist 8.3 pKd 14
pKd 8.3 (Kd 5x10-9 M) [14]
annexin I {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 6.5 pKd 75
pKd 6.5 [75]
fMet-Leu-Phe Peptide Click here for species-specific activity table Hs Full agonist 6.4 pKd 82
pKd 6.4 [82]
[125I-Tyr]Ac2-26 Peptide Ligand is labelled Ligand is radioactive Rn Full agonist 6.1 pKd 14
pKd 6.1 (Kd 8.2x10-7 M) [14]
[125I-Tyr]Ac2-26 Peptide Ligand is labelled Ligand is radioactive Hs Agonist 5.9 pKd 75
pKd 5.9 (Kd 1.3x10-6 M) [75]
CGEN-855A Peptide Hs Full agonist 7.3 pKi 46
pKi 7.3 (Ki 5.41x10-8 M) [46]
LXA4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist ~12.0 pEC50 54
pEC50 ~12.0 (EC50 ~1.1x10-12 M) [54]
resolvin D1 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Hs Full agonist ~11.9 pEC50 54
pEC50 ~11.9 (EC50 ~1.2x10-12 M) [54]
RvD1-ME Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 11.4 pEC50 53
pEC50 11.4 (EC50 3.7x10-12 M) [53]
aspirin-triggered resolvin D1 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Hs Full agonist 11.1 pEC50 53
pEC50 11.1 [53]
WKYMVm Peptide Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 9.0 – 10.1 pEC50 43,45
pEC50 9.0 – 10.1 [43,45]
BMS-986235 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Agonist 9.3 pEC50 2
pEC50 9.3 (EC50 5x10-10 M) [2]
sCKβ8-1 Peptide Hs Full agonist 8.9 – 9.1 pEC50 24
pEC50 8.9 – 9.1 [24]
MMK-1 Peptide Immunopharmacology Ligand Hs Full agonist 8.7 pEC50 47,51
pEC50 8.7 [47,51]
PSMα3 Peptide Hs Full agonist 8.7 pEC50 52
pEC50 8.7 [52]
ACT-389949 Small molecule or natural product Immunopharmacology Ligand Hs Agonist 8.5 pEC50 93
pEC50 8.5 (EC50 3x10-9 M) [93]
Description: FPR2/ALX internalization into monocytes.
humanin {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.5 pEC50 41
pEC50 8.5 [41]
BMS-986235 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 8.3 pEC50 2
pEC50 8.3 (EC50 5x10-9 M) [2]
fMet-Met-Tyr-Ala-Leu-Phe Peptide Click here for species-specific activity table Hs Full agonist 7.8 pEC50 83
pEC50 7.8 [83]
SHAAGtide Peptide Hs Full agonist 7.7 pEC50 24,66
pEC50 7.7 [24,66]
pyrazolone, 1 Small molecule or natural product Ligand has a PDB structure Hs Full agonist 7.4 pEC50 9
pEC50 7.4 [9]
T21/DP107 Peptide Hs Full agonist 7.3 pEC50 95
pEC50 7.3 (EC50 5x10-8 M) [95]
uPar fragment Peptide Hs Full agonist 7.1 pEC50 84
pEC50 7.1 [84]
amyloid β {Sp: Human} Peptide Hs Full agonist 7.0 pEC50 59,98
pEC50 7.0 [59,98]
pyrazolone, 1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Full agonist 6.9 pEC50 43
pEC50 6.9 [43]
CRAMP {Sp: Mouse} Peptide Ligand is endogenous in the given species Immunopharmacology Ligand Mm Full agonist 6.7 – 7.0 pEC50 56
pEC50 6.7 – 7.0 [56]
fMet-Ile-Val-Thr-Leu-Phe Peptide Click here for species-specific activity table Hs Full agonist 6.7 pEC50 83
pEC50 6.7 [83]
serum amyloid A {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 6.6 pEC50 96
pEC50 6.6 (EC50 2.5x10-7 M) [96]
humanin {Sp: Human} Peptide Mm Full agonist 6.0 – 7.0 pEC50 103
pEC50 6.0 – 7.0 [103]
F2L {Sp: Human} Peptide Mm Full agonist 6.4 pEC50 35
pEC50 6.4 (EC50 4x10-7 M) [35]
AG-26 Small molecule or natural product Hs Full agonist 6.3 pEC50 50
pEC50 6.3 [50]
compound R-(-)-5f [PMID: 22607879] Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.3 pEC50 16
pEC50 6.3 (EC50 5.4x10-7 M) [16]
quin-C1 Small molecule or natural product Mm Full agonist 6.2 pEC50 43
pEC50 6.2 [43]
LL-37 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Hs Full agonist 6.0 pEC50 19
pEC50 6.0 [19]
annexin I-(2-26) {Sp: Human} Peptide Click here for species-specific activity table Hs Full agonist 5.8 – 6.1 pEC50 36,42,75,100
pEC50 5.8 – 6.1 [36,42,75,100]
quin-C1 Small molecule or natural product Hs Full agonist 5.7 pEC50 70
pEC50 5.7 [70]
fMet-Ile-Val-Thr-Leu-Phe Peptide Click here for species-specific activity table Mm Full agonist 5.6 pEC50 43,92
pEC50 5.6 [43,92]
fMet-Met-Tyr-Ala-Leu-Phe Peptide Click here for species-specific activity table Mm Full agonist 5.3 pEC50 43
pEC50 5.3 [43]
PrP106-126 Peptide Ligand is endogenous in the given species Hs Agonist 4.6 pEC50 10
pEC50 4.6 [10]
MHC binding peptide Peptide Hs Full agonist 10.0 pIC50 12
pIC50 10.0 [12]
CGEN-855A Peptide Hs Full agonist 6.7 pIC50 46
pIC50 6.7 (IC50 1.89x10-7 M) [46]
Hp(2-20) Peptide Click here for species-specific activity table Hs Agonist - - 5
[5]
N36 Peptide Hs Full agonist - - 60
[60]
F peptide Peptide Hs Full agonist - - 20
[20]
V3 peptide Peptide Hs Full agonist - - 87
[87]
1R-11 Small molecule or natural product Immunopharmacology Ligand Hs Agonist - - 18
[18]
View species-specific agonist tables
Agonist Comments
Listed above are major FPR2/ALX agonists and several agonists for mouse Fpr2 (Fpr-rs2). They are grouped into several classes:
1. Bacteria-derived formyl peptides: The classic tripeptide fMet-Leu-Phe is a low affinity agonist for FPR2/ALX and is not an activator for mouse Fpr2. The PSMα3 peptide from highly pathogenic S. aureus has a pEC50 value of 8.67 and is one of the most potent bacterial formyl peptides for FPR2/ALX.
2. Mitochondria-derived formyl peptides: fMet-Met-Tyr-Ala-Leu-Phe (ND6), fMet-Leu-Lys-Leu-Ile-Val (ND4), and fMet-Tyr-Phe-Ile-Asn-Ile-Leu-Thr-Leu (ND1) are endogenous agonists for FPR2/ALX [83].
3. Lipid mediators: resolvin D1 (RvD1) and lipoxin A4 (LXA4). LXA4 is highly potent in triggering anti-inflammatory functions in animal models. Cell-based studies suggest that FPR2/ALX is a receptor for LXA4 in several published reports [13,26,28], but others failed to identify LXA4-induced GPCR responses [31,40,78]. One of the reasons could be agonist (LXA4) batch difference. A recent study [54] showed that RvD1 and LXA4 selectively activate the beta-arrestin pathway, suggesting that RvD1 and LXA4 might be partial agonists or biased agonists at ALX/FPR2. See [40] for a different outcome in β-arrestin translocation by LXA4.
4. Host-derived non-amyloidogenic peptides: This class includes SHAAGtide, LL-37, CCL-23, humanin, and uPAR(88-274)/D2D3. Annexin and derived peptides are also host-derived non-amyloidogenic peptides, but some of these peptides are less selective between FPR1 and FPR2/ALX.
5. Host-derived amyloidogenic peptides: SAA and Aβ[1-42] are two agonists in this class. They also bind and activate other receptors.
6. HIV-1 envelope peptides: These are T21/DP107, N36, F peptide, and V3 peptide.
7. Prion peptide: PrP (106-126) is the only member of this class, derived from prion proteins.
8. Peptides identified from library screen: This class is represented by WKYMVm and MMK-1. Other peptides with lower potency or affinity are not shown.
9. Synthetic compounds which are FPR2/ALX-specific agonists: Quin-C1, N`-Phenylurea derivatives (AG-26, AG-09/37, AG-09/38, AG-09/42, and AG-09/43), 2-(N-piperazinyl) acetamide derivatives (AG-09/3, AG-09/4, AG-09/73 through AG-09/77, and AG-09/82), and acetohydrazide derivatives (AG-09/7, AG-09/92, AG-09/96, AG-09/101, and AG-09/102). Selected chiral 6-methyl-2, 4-disubstituted pyridazin-3(2H)-compounds are potent mixed FPR1/FPR2/ALX agonists, among which R-(-)-forms generally exhibited higher activity than the S-(+)-enantiomers [16]. Pyrazolone, 4-iodo-substituted compound no. 43 activates FPR2/ALX and mouse Fpr1.

Mouse Fpr2 shares most of its binding properties with human FPR2/ALX. One of the differences is the inability for the mouse Fpr2 to bind and interact with most formylpeptides tested. The exceptions are long peptides such as fMLFII, fMMYALF (from mitochondria), fMIVIL (from L. monocytogenes), which are better agonists with reasonably good EC50 in most functional assays.

Hp(2-20), a peptide from H. pylori induced a rise in intracellular calcium levels in cells tranfected with FPR2/ALX; however the efficacy of this peptide was greater at FPRL2-expressing cells [5].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
quin-C7 Small molecule or natural product Hs Antagonist 5.2 pEC50 104
pEC50 5.2 [104]
isopropylureido-FLFLF Peptide Hs Antagonist 4.3 – 6.0 pEC50 21
pEC50 4.3 – 6.0 [21]
compound 1754-31 [PMID: 23788657] Small molecule or natural product Hs Antagonist 7.1 pIC50 77
pIC50 7.1 [77]
WRWWWW Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.6 pIC50 3
pIC50 6.6 [3]
t-Boc-FLFLF Peptide Click here for species-specific activity table Hs Antagonist 4.3 – 6.0 pIC50 32,94,100
pIC50 4.3 – 6.0 [32,94,100]
FPRL1-inhibitor protein Peptide Hs Antagonist - - 79
[79]
Antagonist Comments
The available FPR2/ALX antagonists are very limited at this time. The recently identified compound (1754-31) is one of the most potent FPR2/ALX antagonists. None of the FPR2/ALX antagonists are found to have inverse agonistic activity. t-Boc-FLFLF is shown in some publications as an antagonist for both FPR1 and FPR2/ALX. In a recent publication, its antagonistic activity is found to be more selective for FPR1 than FPR2/ALX [71].
Allosteric Modulators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PBP10 Peptide Hs Positive 7.0 pIC50 83
pIC50 7.0 [83]
Allosteric Modulator Comments
PBP10 is a cell-permeable, rhodamine B-coupled polyphosphoinositide-binding peptide based on gelsolin a.a. 160-169. PBP10 inhibits neutrophil degranulation and superoxide generation induced by FPR2/ALX agonists but not FPR1 agonists. However, PBP10 does not affect agonist-induced calcium mobilization, suggesting that it is an allosteric modulator of FPR2/ALX mediated functions [30,33].
Immunopharmacology Comments
Formyl peptide receptor type 2 (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. Resolvin D1-mediated activation of FPR2/ALX appears to resolve salivary gland inflammation in a mouse model of Sjögren syndrome [101]. FPR2/ALX receptor agonism is a new therapeutic concept that is being investigated for the development of novel non-steroidal anti-inflammatory agents as modulators of pathological dysregulated inflammation [6-7]. Since endogenous pro-resolving mediators like lipoxin A4 are highly unstable, investigators are designing lipoxin mimetics with improved physicochemical properties [18].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Antigen presentation
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Phospholipase C stimulation
Phospholipase A2 stimulation
Phospholipase D stimulation
References:  26-27,48,57,73-74
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Phospholipase A2 stimulation
Phospholipase D stimulation
Other - See Comments
Comments:  FPR2/ALX joins a small group of chemoattractant/chemokine receptors which share a mechanism of using CD38-dependent cyclic ADP ribose for calcium flux and chemotaxis. Many of these receptors also couple to Gq in addition to Gi proteins.
References:  73-74
Tissue Distribution Click here for help
Most abundant in the lung, followed by spleen and placenta, tissues known to have a relatively high degree of phagocytic cell infiltrates.
Species:  Human
Technique:  Northern blot
References:  26,97
Cloned in several types of leukocytes, including PMN, monocytes and T cells, as well as resident cells such as macrophages, synovial fibroblasts and intestinal epithelial cells.
Species:  Human
Technique:  RT-PCR
References:  13
Human FPR2/ALX is expressed in neutrophils, monocytes, macrophages, immature dendritic cells, and at low levels in T and B cells. FPR2/ALX is also found in epithelial cells, mocroglial cells, astrocytes, hepatocytes, and at low levels in endothelial cells.
Species:  Human
Technique:  RT-PCR
References:  67
Most abundant in neutrophils, followed by spleen and lung.
Species:  Mouse
Technique:  Northern blot
References:  97
Expressed in lung, kidney and leukocytes.
Species:  Rat
Technique:  RNase protection assay
References:  14
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
Calcium mobilization, adherence, chemotaxis
Species:  Human
Tissue:  Monocyte, THP-1 cells
Response measured:  LXA4 increases calcium mobilization, adherence, chemotaxis
References:  64-65
ERK activation
Species:  Human
Tissue:  T cells
Response measured:  ATL stimulate ERK activation
References:  1
IL-8 gene expression and release, NF-κB activation
Species:  Human
Tissue:  Enterocyte
Response measured:  LXA4 and ATL reduce IL-8 and NF-κB activation
References:  37,55
Phagocytosis
Species:  Human
Tissue:  Macrophage
Response measured:  LXA4 stimulates nonphlogistic phagocytosis of apoptotic neutrophils
References:  38
LXA4 reduces IL-8 and NF-κB responses, alters MMP-1 and MMP-3 expression
Species:  Human
Tissue:  Fibroblast
Response measured: 
References:  89-90
PLD activation, arachidonic acid release, PSDP increase
Species:  Human
Tissue:  PMN, HL-60 cells or CHO cells overexpressing human FPR2/ALX
Response measured:  LXA4 and ATL stimulate PLD activation, arachidonic acid release, PSDP, inhibits superoxide anion generation
References:  26-28,62
Physiological Functions Click here for help
Superoxide generation. Some of the FPR2/ALX agonists are known to stimulate neutrophil superoxide generation. This function can play a role in both host defense and tissue injury.
Species:  Human
Tissue:  Neutrophils, monocytes, macrophages
References:  86
Induction of inflammatory gene expression. Several FPR2/ALX agonists have been shown to stimulate NF-κB activation, resulting in the expression of proinflammatory cytokines and metalloproteinases. This activity is FPR2/ALX dependent.
Species:  Human
Tissue:  Neutrophils, synovial fibroblasts, chondrocytes
References:  44,61,90
Chemotaxis. Nearly all FPR2/ALX agonists induce chemotaxis either in neutrophils and monocytes that naturally express this receptor or in FPR2/ALX transfected cell lines. This function is responsible for cell migration, neutrophil and monocyte accumulation in vivo.
Species:  Human
Tissue:  Neutrophils, monocytes, other leukocytes that express FPR2
References:  58,96
LXA4 and ATL regulate gene expression in synovial fibroblasts (e.g. IL-1b, IL-6, IL-8, MMP-1, MMP-3), and in epithelial cells (e.g. IL-8, NF-κB).
Species:  Human
Tissue:  Fibroblast, enterocyte
References:  37,55,89-90
LXA4 and ATL give pro-resolving signals, stimulating non-phlogistic monocyte activation (clacium mobilization, adherence and chemotaxis), and macrophage phagocytosis of apoptotic PMN
Species:  Human
Tissue:  Monocyte and macrophage
References:  38,64-65
LXA4 and ATL give anti-inflammatory signals such as reducing CD11b/CD18, expression, blocking ROS production, NF-κB activation, pro-inflammatory cytokines/chemokines. They also increase anti-inflammatory cytokines/chemokines and transcription corepressor NAB1
Species:  Human
Tissue:  Neutrophils
References:  25,29,81
Anti-inflammatory effect. Several studies have shown that ligands for FPR2/ALX such as LXA4, annexin I peptides and a synthetic small molecule, display anti-inflammatory effects in vivo and in vitro. While some of these effects may result in part from activation of other receptors such as AhR, transgenic expression of FPR2/ALX in mice has shown increased inhibiton of neutrophil infiltration and suppression of TNF-α induced NF-κB activity. A double-blinded, placebo-controlled, randomized clinical trial with 60 patients showed that 15(R/S)-methyl-LXA4 significantly reduced the severity of eczema (Wu et al, 2013).
Species:  Human
Tissue:  Ear skin, synovial fibroblasts
References:  9,22,75,91
Physiological Consequences of Altering Gene Expression Click here for help
Actions of RvD1 in reducing PMN infiltration and regulating select microRNAs were abolished in Fpr2 null mice
Species:  Mouse
Tissue:  Peritoneal exudate
Technique:  Gene knockouts
References:  53,72
Excerbated inflammation (ischemia reperfusion and arthritis). Fpr2 knockout mice exhibit an increased number of adherent and emigrated leukocytes after mesentery ischemia-reperfusion, whereas the number of platelet/neutrophil aggregates were decreased. Fpr2 knockout mice also exhibited an increased carrageenan-induced paw edema and exacerbation and prolongation of K/BxN serum-induced arthritis.
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  8,23
Deficiency in mFpr1 and mFpr2 exacerbated the severity of the infection and increased the mortality of infected mice. The mechanism involved impaired early neutrophil recruitment to the liver with Fpr1 and Fpr2 being sole receptors for neutrophils to sense Listeria chemoattractant signals and for production of bactericidal superoxide.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  63
Overexpression of human FPR2/ALX in transgenic mice results in an increased ability of LXA4 to attenuate neutrophil infiltration to ear skin tissue that are stimulated with LTB4 and PGE2. Mice also display a profound anti-inflammatory phenotype, markedly decreasing PMN infiltration with endogenous LXA4. Moreover, these hFPR2/ALX mice show increased sensitivity in response to the suboptimal doses of exogenous ATLa in vivo, shifting the dose response curve to the left when compared to their non-transgenic littermates. These results provide the compelling evidence for direct functional links between LXA4 and functional roles for human FPR2/ALX in vivo
Species:  Mouse
Tissue:  Peritoneal leukocytes
Technique:  Gene over-expression of human ALX/FPR2 in transgenic mice
References:  22
Fpr2 knockout mice exhibit reduced ovalbumin/alum-induced allergic airway inflammation, associated with lower levels of IL4, IL5 and IL13 in BAL and a reduced recruitment of dendritic cells to draining lymph nodes.
Species:  Mouse
Tissue:  Lung
Technique:  Gene knockouts
References:  11
Knockout of mouse FPR2/ALX (Fpr2), which shares structural and functional features of human FPR2/ALX, results in reduced responsiveness to F2L, an primary agonist for human FPR3.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  35
In vivo administration of 15-epi-LXA4 (aspirin triggered lipoxin A4) reduces intimal hyperplasia after vascular injury in wild-type mice, but is ineffective in Fpr2 knockout mice. Likewise, vascular smooth muscle cells derived from Fpr2 knockout mice are unresponsive to 15-epi-LXA4 in an in vitro wound healing assay.
Species:  Mouse
Tissue:  Blood vessels.
Technique:  Gene knockout.
References:  76
Xenobiotics Influencing Gene Expression Click here for help
Dexamethasone, prednisolone and triamcinolone up-regulate mRNA and protein levels of FPR2/ALX
Species:  Human
Tissue:  PMN, monocytes, lymphocytes, HL-60
Technique:  Flow cytometry, RT-PCR
References:  85
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0009278 abnormal bone marrow cell physiology PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0003009 abnormal cytokine secretion PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0002376 abnormal dendritic cell physiology PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0002419 abnormal innate immunity PMID: 20200280 
Fpr2tm1Rjf Fpr2tm1Rjf/Fpr2tm1Rjf
involves: 129S/SvEv * C57BL/6
MGI:1278319  MP:0002463 abnormal neutrophil physiology PMID: 20107188 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0002281 abnormal respiratory mucosa goblet cell morphology PMID: 20200280 
Fpr2tm1Rjf Fpr2tm1Rjf/Fpr2tm1Rjf
involves: 129S/SvEv * C57BL/6
MGI:1278319  MP:0005164 abnormal response to injury PMID: 20107188 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0008127 decreased dendritic cell number PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0002492 decreased IgE level PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0008495 decreased IgG1 level PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0008497 decreased IgG2b level PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0002460 decreased immunoglobulin level PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0001876 decreased inflammatory response PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0008567 decreased interferon-gamma secretion PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0008673 decreased interleukin-13 secretion PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0008688 decreased interleukin-2 secretion PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0008700 decreased interleukin-4 secretion PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0008703 decreased interleukin-5 secretion PMID: 20200280 
Fpr2tm1Rjf Fpr2tm1Rjf/Fpr2tm1Rjf
involves: 129S/SvEv * C57BL/6
MGI:1278319  MP:0003799 impaired macrophage migration PMID: 20107188 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0003799 impaired macrophage migration PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0008720 impaired neutrophil migration PMID: 20200280 
Fpr2tm1Rjf Fpr2tm1Rjf/Fpr2tm1Rjf
involves: 129S/SvEv * C57BL/6
MGI:1278319  MP:0005088 increased acute inflammation PMID: 20107188 
Fpr2tm1Rjf Fpr2tm1Rjf/Fpr2tm1Rjf
involves: 129S/SvEv * C57BL/6
MGI:1278319  MP:0003724 increased susceptibility to induced arthritis PMID: 20107188 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2
MGI:1278319  MP:0002217 small lymph nodes PMID: 20200280 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Aspirin exacerbated respiratory diseases
References:  49
Disease:  Cardiovascular disease
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Single nucleotide polymorphism Human - A single nucleotide mutation (A/G) was detected in the core promoter of one subject with history of cardiovascular disease and of his two daughters 88
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Association of FPR2 polymorphisms and aspirin exacerbated respiratory diseases -- the minor allele frequency of FPR2 -4209T>G (rs1769490) in intron 2 was significantly lower in the AERD group (n=170) than in the ATA group (n=268). Asthmatic homozygotes for FPR2 -4209T>G minor allele exhibited significantly higher FPR2 protein expression in CD14-positive monocytes than did those with the common allele of FPR2 -4209T>G allele (P=0.01). There was no difference in the expression of the wild form and the exon 2 deleted variant form of FPR2 gene according to the genotypes of FPR2 -4209T>G. The minor allele at FPR2 -4209T>G may have a protective role against the development of AERD, via increase of ALX/FPR2 protein expression in inflammatory cells.
SNP accession: 
References:  49
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The homozygous GG genotype of the FPRL1 -6136G>T polymorphism was significantly lower in subjects with chronic urticaria in a case control study.
References:  102
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A single nucleotide mutation (A/G) was detected in the core promoter of one subject with history of cardiovascular disease and of his two daughters. This mutation reduced ∼35-90% the promoter activity in vitro. Moreover, neutrophils from individuals carrying the A/G variant displayed ∼10- and 3-fold reduction in FPR2/ALX mRNA and protein, respectively, compared with cells from their relatives or healthy volunteers expressing the wild-type allele. These results uncover FPR2/ALX transcriptional regulation and provide the first evidence of mutations that affect ALX/FPR2 transcription, thus opening new opportunities for the understanding of the LXA4-FPR2/ALX axis in human disease.
References:  88
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The T-allele of a -7893C>T polymorphism of the FPRL1 gene was associated with coronary artery disease in a case-control study, but did not change the transcriptional activity of the gene promoter.
SNP accession: 
References:  99
General Comments
The nomenclature for this receptor is outlined in the 2022 NC-IUPHAR review by Qin et al. [80].

It is important to validate chemical structures of LXA4, ATL and RvD1 before carrying out receptor assays because these ligands are chemically fragile and require precise working conditions at the bench. Also, it is noteworthy that LXA4 and RvD1 are subject to rapid metabolic conversion by mammalian cells and cell lines.

References

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Magnus Bäck, Nan Chiang, Sven-Erik Dahlén, Jeffrey Drazen, Jilly F. Evans, G. Enrico Rovati, Charles N. Serhan, Takao Shimizu, Takehiko Yokomizo.
Formylpeptide receptors: FPR2. Last modified on 19/04/2024. Accessed on 10/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=223.