Protease-activated receptor 2

F2RL1

Identifiers

F2RL1, GPR11, PAR2, Protease activated receptor 2, F2R like trypsin receptor 1

External IDs

MGI: 101910 HomoloGene: 21087 GeneCards: F2RL1

Gene location (Human)

Chr.	Chromosome 5 (human)^[1]

Band	No data available	Start	76,818,933 bp^[1]
Band	No data available	End	76,835,315 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 13 (mouse)^[2]

Band	No data available	Start	95,511,732 bp^[2]
Band	No data available	End	95,525,227 bp^[2]

RNA expression pattern

More reference expression data

Gene ontology
Molecular function	• G-protein coupled receptor activity • signal transducer activity • thrombin-activated receptor activity • G-protein beta-subunit binding • protein binding • G-protein alpha-subunit binding • receptor binding • receptor activity
Cellular component	• integral component of membrane • Golgi apparatus • pseudopodium • membrane • plasma membrane • integral component of plasma membrane • early endosome
Biological process	• positive regulation of Rho protein signal transduction • establishment of endothelial barrier • chemokine (C-C motif) ligand 2 secretion • G-protein coupled receptor signaling pathway • thrombin-activated receptor signaling pathway • neutrophil activation • positive regulation of phagocytosis, engulfment • positive regulation of toll-like receptor 3 signaling pathway • positive regulation of eosinophil degranulation • positive regulation of interleukin-6 secretion • positive regulation of neutrophil mediated killing of gram-negative bacterium • negative regulation of tumor necrosis factor-mediated signaling pathway • immune system process • positive regulation of cell migration • positive regulation of cytosolic calcium ion concentration • blood coagulation • positive regulation of JNK cascade • positive regulation of leukocyte chemotaxis • negative regulation of JNK cascade • leukocyte proliferation • regulation of JNK cascade • positive regulation of pseudopodium assembly • chemokine secretion • positive regulation of renin secretion into blood stream • interleukin-1 beta secretion • defense response to virus • positive regulation of chemotaxis • positive regulation of ERK1 and ERK2 cascade • positive regulation of cytokine secretion involved in immune response • positive regulation of toll-like receptor 4 signaling pathway • positive regulation of I-kappaB kinase/NF-kappaB signaling • positive regulation of interleukin-8 secretion • positive regulation of toll-like receptor 2 signaling pathway • positive regulation of phosphatidylinositol 3-kinase signaling • positive regulation of superoxide anion generation • interleukin-10 secretion • positive regulation of glomerular filtration • regulation of blood coagulation • inflammatory response • innate immune response • interferon-gamma secretion • negative regulation of chemokine secretion • mature conventional dendritic cell differentiation • negative regulation of toll-like receptor 3 signaling pathway • positive regulation of actin filament depolymerization • leukocyte migration • regulation of I-kappaB kinase/NF-kappaB signaling • positive regulation of transcription from RNA polymerase II promoter • positive regulation of positive chemotaxis • signal transduction • T cell activation involved in immune response • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway • positive regulation of blood vessel diameter
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


2150


14063

Ensembl


ENSG00000164251


ENSMUSG00000021678

UniProt


P55085


P55086

RefSeq (mRNA)


NM_005242


NM_007974

RefSeq (protein)


NP_005233


NP_032000

Location (UCSC)

Chr 5: 76.82 – 76.84 Mb

Chr 5: 95.51 – 95.53 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Protease activated receptor 2 (PAR2) also known as coagulation factor II (thrombin) receptor-like 1 (F2RL1) or G-protein coupled receptor 11 (GPR11) is a protein that in humans is encoded by the F2RL1 gene. PAR2 modulates inflammatory responses, obesity,^[5] metabolism,^[6] and acts as a sensor for proteolytic enzymes generated during infection.^[7]

Gene

The F2RL1 gene contains two exons and is widely expressed in human tissues. The predicted protein sequence is 83% identical to the mouse receptor sequence.^[8]

Mechanism of activation

PAR2 is a member of the large family of 7-transmembrane receptors that couple to guanosine-nucleotide-binding proteins. PAR2 is also a member of the protease-activated receptor family. It is activated by trypsin, but not by thrombin. It is activated by proteolytic cleavage of its extracellular amino terminus. The new amino terminus functions as a tethered ligand and activates the receptor. Additionally, these receptors can be activated by exogenous proteases, such as house dust mite protein Der P9.^[9] These receptors can also be activated non-protealytically, by exogenous peptide sequences that mimic the final amino acids of the tethered ligand.^[10]

Agonists and antagonists

Potent and selective small molecule agonists and antagonists for PAR2 have been discovered.^[11]^[12]^[13]

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000164251 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021678 - Ensembl, May 2017
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Lim J, Iyer A, Liu L, Suen JY, Lohman RJ, Seow V, Yau MK, Brown L, Fairlie DP (December 2013). "Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism". FASEB Journal. 27 (12): 4757–67. PMID 23964081. doi:10.1096/fj.13-232702.
↑ Badeanlou L, Furlan-Freguia C, Yang G, Ruf W, Samad F (October 2011). "Tissue factor-protease-activated receptor 2 signaling promotes diet-induced obesity and adipose inflammation". Nature Medicine. 17 (11): 1490–7. PMC 3210891 . PMID 22019885. doi:10.1038/nm.2461.
↑ Lee SE, Jeong SK, Lee SH (November 2010). "Protease and protease-activated receptor-2 signaling in the pathogenesis of atopic dermatitis". Yonsei Medical Journal. 51 (6): 808–22. PMC 2995962 . PMID 20879045. doi:10.3349/ymj.2010.51.6.808.
↑ "Entrez Gene: F2RL1 coagulation factor II (thrombin) receptor-like 1".
↑ Sun G, Stacey MA, Schmidt M, Mori L, Mattoli S (July 2001). "Interaction of mite allergens Der p3 and Der p9 with protease-activated receptor-2 expressed by lung epithelial cells". Journal of Immunology. 167 (2): 1014–21. PMID 11441110. doi:10.4049/jimmunol.167.2.1014.
↑ Kawabata A, Kanke T, Yonezawa D, Ishiki T, Saka M, Kabeya M, Sekiguchi F, Kubo S, Kuroda R, Iwaki M, Katsura K, Plevin R (June 2004). "Potent and metabolically stable agonists for protease-activated receptor-2: evaluation of activity in multiple assay systems in vitro and in vivo". The Journal of Pharmacology and Experimental Therapeutics. 309 (3): 1098–107. PMID 14976227. doi:10.1124/jpet.103.061010.
↑ Gardell LR, Ma JN, Seitzberg JG, Knapp AE, Schiffer HH, Tabatabaei A, Davis CN, Owens M, Clemons B, Wong KK, Lund B, Nash NR, Gao Y, Lameh J, Schmelzer K, Olsson R, Burstein ES (December 2008). "Identification and characterization of novel small-molecule protease-activated receptor 2 agonists". The Journal of Pharmacology and Experimental Therapeutics. 327 (3): 799–808. PMID 18768780. doi:10.1124/jpet.108.142570.
↑ Barry GD, Suen JY, Le GT, Cotterell A, Reid RC, Fairlie DP (October 2010). "Novel agonists and antagonists for human protease activated receptor 2". Journal of Medicinal Chemistry. 53 (20): 7428–40. PMID 20873792. doi:10.1021/jm100984y.
↑ Yau MK, Liu L, Suen JY, Lim J, Lohman RJ, Jiang Y, Cotterell AJ, Barry GD, Mak JY, Vesey DA, Reid RC, Fairlie DP (December 2016). "PAR2 Modulators Derived from GB88". ACS Medicinal Chemistry Letters. 7 (12): 1179–1184. PMC 5150695 . PMID 27994760. doi:10.1021/acsmedchemlett.6b00306.

External links

"Protease-Activated Receptors: PAR2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

Cell surface receptor: G protein–coupled receptors

Class A: Rhodopsin-like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3
Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)
Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)
Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine D1 D2 D3 D4 D5 GHB receptor Histamine H1 H2 H3 H4 Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 1 2 FPRL1 OXE Prostaglandin DP (1 2), EP (1 2 3 4), FP Prostacyclin Thromboxane
Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide

B/W (1
2)
FF (1
2)
S
Y (1
2
4
5)
Neuromedin (B
U (1
2))
Neurotensin (1
2)

Other

Anaphylatoxin (C3a
C5a)
Angiotensin (1
2)
Apelin
Bombesin
- BRS3
- GRPR
- NMBR)
- Bradykinin (B1
- B2)
Chemokine
Cholecystokinin (A
B)
Endothelin
- A
- B
Formyl peptide (1
2
3)
FSH
Galanin (1
2
3)
Gonadotropin-releasing hormone (1
2)
Ghrelin
Kisspeptin
Luteinizing hormone/choriogonadotropin
MAS (1
1L
D
E
F
G
X1
X2
X3
X4)
Melanocortin (1
2
3
4
5)
MCHR (1
2)
Motilin
Opioid (Delta
Kappa
Mu
Nociceptin & Zeta, but not Sigma)
Orexin (1
2)
Oxytocin
Prokineticin (1
2)
Prolactin-releasing peptide
Relaxin (1
2
3
4)
Somatostatin (1
2
3
4
5)
Tachykinin (1
2
3)
Thyrotropin
Thyrotropin-releasing hormone
Urotensin-II
Vasopressin (1A
1B
2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)
Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin-like

Adhesion	ADGRG (1 2 3 4 5 6 7)
Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)
Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth-hormone-releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60 Vomeronasal receptor)
Other	Calcium-sensing receptor GABAB (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)
Smoothened	Smoothened

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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