Protease activated receptor 2

Coagulation factor II (thrombin) receptor-like 1
Identifiers
Symbols	F2RL1; GPR11; PAR2
External IDs	OMIM: 600933 MGI: 101910 HomoloGene: 21087 IUPHAR: PAR2 GeneCards: F2RL1 Gene
Gene Ontology Molecular function • G-protein alpha-subunit binding • signal transducer activity • receptor activity • G-protein coupled receptor activity • G-protein coupled receptor activity • receptor binding • protein binding • thrombin receptor activity • G-protein beta-subunit binding Cellular component • Golgi apparatus • plasma membrane • integral to plasma membrane • pseudopodium Biological process • T cell activation involved in immune response • positive regulation of leukocyte chemotaxis • positive regulation of cytokine secretion involved in immune response • inflammatory response • G-protein coupled receptor signaling pathway • G-protein coupled receptor signaling pathway • elevation of cytosolic calcium ion concentration • elevation of cytosolic calcium ion concentration • negative regulation of tumor necrosis factor-mediated signaling pathway • positive regulation of phosphatidylinositol 3-kinase cascade • regulation of blood coagulation • positive regulation of cell migration • positive regulation of actin filament depolymerization • positive regulation of pseudopodium assembly • positive regulation of superoxide anion generation • positive regulation of toll-like receptor 2 signaling pathway • negative regulation of toll-like receptor 3 signaling pathway • positive regulation of toll-like receptor 3 signaling pathway • positive regulation of toll-like receptor 4 signaling pathway • positive regulation of Rho protein signal transduction • positive regulation of Rho protein signal transduction • chemokine (C-C motif) ligand 2 secretion • neutrophil activation • regulation of I-kappaB kinase/NF-kappaB cascade • positive regulation of I-kappaB kinase/NF-kappaB cascade • positive regulation of eosinophil degranulation • innate immune response • positive regulation of vasodilation • positive regulation of transcription from RNA polymerase II promoter • regulation of JNK cascade • negative regulation of JNK cascade • positive regulation of JNK cascade • interleukin-1 beta secretion • leukocyte migration • positive regulation of chemotaxis • positive regulation of positive chemotaxis • defense response to virus • positive regulation of phagocytosis, engulfment • establishment of endothelial barrier • positive regulation of ERK1 and ERK2 cascade • positive regulation of ERK1 and ERK2 cascade • leukocyte proliferation • positive regulation of neutrophil mediated killing of gram-negative bacterium • interleukin-10 secretion • interferon-gamma secretion • chemokine secretion • negative regulation of chemokine secretion • mature dendritic cell differentiation • mature dendritic cell differentiation • positive regulation of interleukin-8 secretion • positive regulation of interleukin-6 secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2150	14063
Ensembl	ENSG00000164251	ENSMUSG00000021678
UniProt	P55085	P55086
RefSeq (mRNA)	NM_005242.4	NM_007974.4
RefSeq (protein)	NP_005233.3	NP_032000.3
Location (UCSC)	Chr 5: 76.11 – 76.13 Mb	Chr 13: 96.28 – 96.3 Mb
PubMed search	[1]	[2]

Protease activated receptor 2 (PAR2) or Coagulation factor II (thrombin) receptor-like 1, is a protein encoded by the F2RL1 gene in humans.

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. These receptors can also be activated non-protealytically, by exogenous peptide sequences that mimic the final amino acids of the tethered ligand. Recently, potent and selective small molecule agonists for these receptors have also been discovered but are not currently widely available. 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.

See also

• Protease-activated receptor

External links

• "Protease-Activated Receptors: PAR2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3020. 

Further reading

• Kunzelmann K, Schreiber R, König J, Mall M (2003). "Ion transport induced by proteinase-activated receptors (PAR2) in colon and airways.". Cell Biochem. Biophys. 36 (2–3): 209–14. doi:10.1385/CBB:36:2-3:209. PMID 12139406. 
• Kawabata A (2004). "PAR-2: structure, function and relevance to human diseases of the gastric mucosa". Expert reviews in molecular medicine 4 (16): 1–17. doi:10.1017/S1462399402004799. PMID 14585156. 
• Bushell T (2007). "The emergence of proteinase-activated receptor-2 as a novel target for the treatment of inflammation-related CNS disorders". J. Physiol. (Lond.) 581 (Pt 1): 7–16. doi:10.1113/jphysiol.2007.129577. PMC 2075212. PMID 17347265. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2075212. 
• Nystedt S, Emilsson K, Larsson AK, et al. (1995). "Molecular cloning and functional expression of the gene encoding the human proteinase-activated receptor 2". Eur. J. Biochem. 232 (1): 84–9. doi:10.1111/j.1432-1033.1995.tb20784.x. PMID 7556175. 
• Santulli RJ, Derian CK, Darrow AL, et al. (1995). "Evidence for the presence of a protease-activated receptor distinct from the thrombin receptor in human keratinocytes". Proc. Natl. Acad. Sci. U.S.A. 92 (20): 9151–5. doi:10.1073/pnas.92.20.9151. PMC 40942. PMID 7568091. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=40942. 
• Nystedt S, Emilsson K, Wahlestedt C, Sundelin J (1994). "Molecular cloning of a potential proteinase activated receptor". Proc. Natl. Acad. Sci. U.S.A. 91 (20): 9208–12. doi:10.1073/pnas.91.20.9208. PMC 44781. PMID 7937743. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=44781. 
• Mirza H, Yatsula V, Bahou WF (1996). "The proteinase activated receptor-2 (PAR-2) mediates mitogenic responses in human vascular endothelial cells". J. Clin. Invest. 97 (7): 1705–14. doi:10.1172/JCI118597. PMC 507235. PMID 8601636. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=507235. 
• Bohm SK, Kong W, Bromme D, et al. (1996). "Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2". Biochem. J. 314 (3): 1009–16. PMC 1217107. PMID 8615752. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1217107. 
• Böhm SK, Khitin LM, Grady EF, et al. (1996). "Mechanisms of desensitization and resensitization of proteinase-activated receptor-2". J. Biol. Chem. 271 (36): 22003–16. doi:10.1074/jbc.271.36.22003. PMID 8703006. 
• Kahn M, Ishii K, Kuo WL, et al. (1996). "Conserved structure and adjacent location of the thrombin receptor and protease-activated receptor 2 genes define a protease-activated receptor gene cluster". Mol. Med. 2 (3): 349–57. PMC 2230143. PMID 8784787. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2230143. 
• Molino M, Barnathan ES, Numerof R, et al. (1997). "Interactions of mast cell tryptase with thrombin receptors and PAR-2". J. Biol. Chem. 272 (7): 4043–9. doi:10.1074/jbc.272.7.4043. PMID 9020112. 
• Howells GL, Macey MG, Chinni C, et al. (1997). "Proteinase-activated receptor-2: expression by human neutrophils". J. Cell. Sci. 110 (7): 881–7. PMID 9133675. 
• D'Andrea MR, Derian CK, Leturcq D, et al. (1998). "Characterization of protease-activated receptor-2 immunoreactivity in normal human tissues". J. Histochem. Cytochem. 46 (2): 157–64. PMID 9446822. 
• Guyonnet Dupérat V, Jacquelin B, Boisseau P, et al. (1998). "Protease-activated receptor genes are clustered on 5q13". Blood 92 (1): 25–31. PMID 9639495. 
• Steinhoff M, Corvera CU, Thoma MS, et al. (1999). "Proteinase-activated receptor-2 in human skin: tissue distribution and activation of keratinocytes by mast cell tryptase". Exp. Dermatol. 8 (4): 282–94. doi:10.1111/j.1600-0625.1999.tb00383.x. PMID 10439226. 
• Takeuchi T, Harris JL, Huang W, et al. (2000). "Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates". J. Biol. Chem. 275 (34): 26333–42. doi:10.1074/jbc.M002941200. PMID 10831593. 
• Loew D, Perrault C, Morales M, et al. (2000). "Proteolysis of the exodomain of recombinant protease-activated receptors: prediction of receptor activation or inactivation by MALDI mass spectrometry". Biochemistry 39 (35): 10812–22. doi:10.1021/bi0003341. PMID 10978167. 
• Knight DA, Lim S, Scaffidi AK, et al. (2001). "Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma". J. Allergy Clin. Immunol. 108 (5): 797–803. doi:10.1067/mai.2001.119025. PMID 11692107. 
• Miike S, McWilliam AS, Kita H (2002). "Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2". J. Immunol. 167 (11): 6615–22. PMID 11714832. 
• Asokananthan N, Graham PT, Fink J, et al. (2002). "Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells". J. Immunol. 168 (7): 3577–85. PMID 11907122. 

• Wong, D. M.; Tam, V.; Lam, R. et al. (2010). "Protease-activated receptor 2 has pivotal roles in cellular mechanisms involved in experimental periodontitis.". Infect. Immun. 78 (7): 629-38. PMID 19933835. 

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