Protease-activated receptor 2

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F2RL1
Identifiers
Aliases F2RL1, GPR11, PAR2, Protease activated receptor 2, F2R like trypsin receptor 1
External IDs MGI: 101910 HomoloGene: 21087 GeneCards: F2RL1
Gene location (Human)
Chromosome 5 (human)
Chr. Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for F2RL1
Genomic location for F2RL1
Band 5q13.3 Start 76,818,933 bp[1]
End 76,835,315 bp[1]
RNA expression pattern
PBB GE F2RL1 213506 at fs.png

PBB GE F2RL1 206429 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
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[edit]

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[edit]

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[edit]

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

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164251 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021678 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ 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. 
  6. ^ 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 3210891Freely accessible. PMID 22019885. doi:10.1038/nm.2461. 
  7. ^ 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 2995962Freely accessible. PMID 20879045. doi:10.3349/ymj.2010.51.6.808. 
  8. ^ "Entrez Gene: F2RL1 coagulation factor II (thrombin) receptor-like 1". 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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 5150695Freely accessible. PMID 27994760. doi:10.1021/acsmedchemlett.6b00306. 

Further reading[edit]

External links[edit]

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