Protease activated receptor 2

Coagulation factor II (thrombin) receptor-like 1

Identifiers

F2RL1; GPR11; PAR2

External IDs

OMIM: 600933 MGI: 101910 HomoloGene: 21087 IUPHAR: PAR2 GeneCards: F2RL1 Gene

Gene Ontology
Molecular function	• receptor activity • G-protein coupled receptor activity • receptor binding • thrombin receptor activity
Cellular component	• Golgi apparatus • plasma membrane • plasma membrane • integral to plasma membrane
Biological process	• positive regulation of leukocyte chemotaxis • G-protein coupled receptor protein signaling pathway • elevation of cytosolic calcium ion concentration • regulation of blood coagulation • positive regulation of positive chemotaxis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

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.^[1] These receptors can also be activated non-protealytically, by exogenous peptide sequences that mimic the final amino acids of the tethered ligand.^[2] Recently, potent and selective small molecule agonists for these receptors have also been discovered but are not currently widely available.^[3] 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.^[4]

1 See also
2 References
3 External links
4 Further reading

References

^ 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". J. Immunol. 167 (2): 1014–21. PMID 11441110. http://www.jimmunol.org/cgi/content/abstract/167/2/1014.
^ Kawabata A, Kanke T, Yonezawa D, et al. (June 2004). "Potent and metabolically stable agonists for protease-activated receptor-2: evaluation of activity in multiple assay systems in vitro and in vivo". J. Pharmacol. Exp. Ther. 309 (3): 1098–107. doi:10.1124/jpet.103.061010. PMID 14976227.
^ Gardell LR, Ma JN, Seitzberg JG, et al. (December 2008). "Identification and characterization of novel small-molecule protease-activated receptor 2 agonists". J. Pharmacol. Exp. Ther. 327 (3): 799–808. doi:10.1124/jpet.108.142570. PMID 18768780.
^ "Entrez Gene: F2RL1 coagulation factor II (thrombin) receptor-like 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2150.

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.

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 ( Pt 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 ( Pt 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.

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

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) · 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) · GHB receptor · 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

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, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)

Other	Calcium-sensing receptor · GABA B (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

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

Protease activated receptor 2

Contents

See also

References

External links

Further reading