ID PAR2_HUMAN Reviewed; 397 AA. AC P55085; Q13317; Q13346; Q53XJ8; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 24-JAN-2024, entry version 206. DE RecName: Full=Proteinase-activated receptor 2; DE Short=PAR-2; DE AltName: Full=Coagulation factor II receptor-like 1; DE AltName: Full=G-protein coupled receptor 11; DE AltName: Full=Thrombin receptor-like 1; DE Contains: DE RecName: Full=Proteinase-activated receptor 2, alternate cleaved 1; DE Contains: DE RecName: Full=Proteinase-activated receptor 2, alternate cleaved 2; DE Flags: Precursor; GN Name=F2RL1; Synonyms=GPR11, PAR2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY. RX PubMed=7556175; DOI=10.1111/j.1432-1033.1995.tb20784.x; RA Nystedt S., Emilsson K., Larsson A.-K., Stroembeck B., Sundelin J.; RT "Molecular cloning and functional expression of the gene encoding the human RT proteinase-activated receptor 2."; RL Eur. J. Biochem. 232:84-89(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Kidney; RX PubMed=8615752; DOI=10.1042/bj3141009; RA Boehm S.K., Kong W., Broemme D., Smeekens S.P., Anderson D.C., RA Connolly A.J., Kahn M.L., Nelken N.A., Coughlin S.R., Payan D.G., RA Bunnett N.W.; RT "Molecular cloning, expression and potential functions of the human RT proteinase-activated receptor-2."; RL Biochem. J. 314:1009-1016(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH COPS5. RX PubMed=16410250; DOI=10.1074/jbc.m510784200; RA Luo W., Wang Y., Hanck T., Stricker R., Reiser G.; RT "Jab1, a novel protease-activated receptor-2 (PAR-2)-interacting protein, RT is involved in PAR-2-induced activation of activator protein-1."; RL J. Biol. Chem. 281:7927-7936(2006). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PHE-21; GLN-270 AND RP ALA-291. RG SeattleSNPs variation discovery resource; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary, and Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-397. RX PubMed=8784787; DOI=10.1007/bf03401632; RA Kahn M.L., Ishii K., Kuo W.L., Piper M., Connolly A.J., Shi Y.P., Wu R., RA Lin C.C., Coughlin S.R.; RT "Conserved structure and adjacent location of the thrombin receptor and RT protease-activated receptor 2 genes define a protease-activated receptor RT gene cluster."; RL Mol. Med. 2:349-357(1996). RN [9] RP ACTIVATION BY MAST CELL TRYPTASE. RX PubMed=9020112; DOI=10.1074/jbc.272.7.4043; RA Molino M., Barnathan E.S., Numerof R., Clark J., Dreyer M., Cumashi A., RA Hoxie J.A., Schechter N., Woolkalis M., Brass L.F.; RT "Interactions of mast cell tryptase with thrombin receptors and PAR-2."; RL J. Biol. Chem. 272:4043-4049(1997). RN [10] RP FUNCTION IN EPITHELIAL BARRIER PROTECTION. RX PubMed=10086357; DOI=10.1038/18223; RA Cocks T.M., Fong B., Chow J.M., Anderson G.P., Frauman A.G., Goldie R.G., RA Henry P.J., Carr M.J., Hamilton J.R., Moffatt J.D.; RT "A protective role for protease-activated receptors in the airways."; RL Nature 398:156-160(1999). RN [11] RP TRANSACTIVATION BY F2R. RX PubMed=10788464; DOI=10.1074/jbc.275.18.13502; RA O'Brien P.J., Prevost N., Molino M., Hollinger M.K., Woolkalis M.J., RA Woulfe D.S., Brass L.F.; RT "Thrombin responses in human endothelial cells. Contributions from RT receptors other than PAR1 include the transactivation of PAR2 by thrombin- RT cleaved PAR1."; RL J. Biol. Chem. 275:13502-13509(2000). RN [12] RP FUNCTION, AND MUTAGENESIS OF SER-363 AND THR-366. RX PubMed=10725339; DOI=10.1083/jcb.148.6.1267; RA DeFea K.A., Zalevsky J., Thoma M.S., Dery O., Mullins R.D., Bunnett N.W.; RT "beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is RT required for intracellular targeting of activated ERK1/2."; RL J. Cell Biol. 148:1267-1281(2000). RN [13] RP ACTIVATION BY ST14. RX PubMed=10831593; DOI=10.1074/jbc.m002941200; RA Takeuchi T., Harris J.L., Huang W., Yan K.W., Coughlin S.R., Craik C.S.; RT "Cellular localization of membrane-type serine protease 1 and RT identification of protease-activated receptor-2 and single-chain urokinase- RT type plasminogen activator as substrates."; RL J. Biol. Chem. 275:26333-26342(2000). RN [14] RP ACTIVATION BY COAGULATION FACTORS VII AND XA. RX PubMed=10805786; DOI=10.1073/pnas.97.10.5255; RA Camerer E., Huang W., Coughlin S.R.; RT "Tissue factor- and factor X-dependent activation of protease-activated RT receptor 2 by factor VIIa."; RL Proc. Natl. Acad. Sci. U.S.A. 97:5255-5260(2000). RN [15] RP FUNCTION, AND ACTIVATION BY GINGIPAINS. RX PubMed=11447194; DOI=10.1128/iai.69.8.5121-5130.2001; RA Lourbakos A., Potempa J., Travis J., D'Andrea M.R., Andrade-Gordon P., RA Santulli R., Mackie E.J., Pike R.N.; RT "Arginine-specific protease from Porphyromonas gingivalis activates RT protease-activated receptors on human oral epithelial cells and induces RT interleukin-6 secretion."; RL Infect. Immun. 69:5121-5130(2001). RN [16] RP FUNCTION IN JNK AND NF-KAPPA-B PATHWAYS. RX PubMed=11413129; DOI=10.1074/jbc.m100377200; RA Kanke T., Macfarlane S.R., Seatter M.J., Davenport E., Paul A., RA McKenzie R.C., Plevin R.; RT "Proteinase-activated receptor-2-mediated activation of stress-activated RT protein kinases and inhibitory kappa B kinases in NCTC 2544 RT keratinocytes."; RL J. Biol. Chem. 276:31657-31666(2001). RN [17] RP FUNCTION, AND ACTIVATION BY DUST MITE ALLERGENS. RX PubMed=11441110; DOI=10.4049/jimmunol.167.2.1014; RA Sun G., Stacey M.A., Schmidt M., Mori L., Mattoli S.; RT "Interaction of mite allergens Der p3 and Der p9 with protease-activated RT receptor-2 expressed by lung epithelial cells."; RL J. Immunol. 167:1014-1021(2001). RN [18] RP FUNCTION IN INFLAMMATORY RESPONSE. RX PubMed=11714832; DOI=10.4049/jimmunol.167.11.6615; RA Miike S., McWilliam A.S., Kita H.; RT "Trypsin induces activation and inflammatory mediator release from human RT eosinophils through protease-activated receptor-2."; RL J. Immunol. 167:6615-6622(2001). RN [19] RP GLYCOSYLATION AT ASN-30 AND ASN-222, AND MUTAGENESIS OF ASN-30 AND ASN-222. RX PubMed=12171601; DOI=10.1042/bj20020706; RA Compton S.J., Sandhu S., Wijesuriya S.J., Hollenberg M.D.; RT "Glycosylation of human proteinase-activated receptor-2 (hPAR2): role in RT cell surface expression and signalling."; RL Biochem. J. 368:495-505(2002). RN [20] RP POSSIBLE INVOLVEMENT IN ALLERGIC DERMATITIS. RX PubMed=11859856; DOI=10.1254/jjp.88.77; RA Kawagoe J., Takizawa T., Matsumoto J., Tamiya M., Meek S.E., Smith A.J., RA Hunter G.D., Plevin R., Saito N., Kanke T., Fujii M., Wada Y.; RT "Effect of protease-activated receptor-2 deficiency on allergic dermatitis RT in the mouse ear."; RL Jpn. J. Pharmacol. 88:77-84(2002). RN [21] RP DEACTIVATION BY NEUTROPHIL ELASTASE AND CATHEPSIN G. RX PubMed=12594060; DOI=10.1165/rcmb.4908; RA Dulon S., Cande C., Bunnett N.W., Hollenberg M.D., Chignard M., Pidard D.; RT "Proteinase-activated receptor-2 and human lung epithelial cells: disarming RT by neutrophil serine proteinases."; RL Am. J. Respir. Cell Mol. Biol. 28:339-346(2003). RN [22] RP POSSIBLE INVOLVEMENT IN SKIN DISEASES. RX PubMed=14519665; DOI=10.1096/fj.02-1112com; RA Seeliger S., Derian C.K., Vergnolle N., Bunnett N.W., Nawroth R., RA Schmelz M., Von Der Weid P.Y., Buddenkotte J., Sunderkotter C., Metze D., RA Andrade-Gordon P., Harms E., Vestweber D., Luger T.A., Steinhoff M.; RT "Proinflammatory role of proteinase-activated receptor-2 in humans and mice RT during cutaneous inflammation in vivo."; RL FASEB J. 17:1871-1885(2003). RN [23] RP FUNCTION. RX PubMed=12832443; DOI=10.1189/jlb.0702351; RA Bolton S.J., McNulty C.A., Thomas R.J., Hewitt C.R., Wardlaw A.J.; RT "Expression of and functional responses to protease-activated receptors on RT human eosinophils."; RL J. Leukoc. Biol. 74:60-68(2003). RN [24] RP MUTAGENESIS OF 355-ALA--SER-363. RX PubMed=14607272; DOI=10.1016/s0898-6568(03)00095-0; RA Seatter M.J., Drummond R., Kanke T., Macfarlane S.R., Hollenberg M.D., RA Plevin R.; RT "The role of the C-terminal tail in protease-activated receptor-2-mediated RT Ca2+ signalling, proline-rich tyrosine kinase-2 activation, and mitogen- RT activated protein kinase activity."; RL Cell. Signal. 16:21-29(2004). RN [25] RP FUNCTION. RX PubMed=15155775; DOI=10.1189/jlb.0503221; RA Shpacovitch V.M., Varga G., Strey A., Gunzer M., Mooren F., Buddenkotte J., RA Vergnolle N., Sommerhoff C.P., Grabbe S., Gerke V., Homey B., RA Hollenberg M., Luger T.A., Steinhoff M.; RT "Agonists of proteinase-activated receptor-2 modulate human neutrophil RT cytokine secretion, expression of cell adhesion molecules, and migration RT within 3-D collagen lattices."; RL J. Leukoc. Biol. 76:388-398(2004). RN [26] RP UBIQUITINATION BY CBL. RX PubMed=15708858; DOI=10.1074/jbc.m500109200; RA Jacob C., Cottrell G.S., Gehringer D., Schmidlin F., Grady E.F., RA Bunnett N.W.; RT "c-Cbl mediates ubiquitination, degradation, and down-regulation of human RT protease-activated receptor 2."; RL J. Biol. Chem. 280:16076-16087(2005). RN [27] RP FUNCTION IN ENDOTHELIAL BARRIER PROTECTION. RX PubMed=16359518; DOI=10.1111/j.1538-7836.2005.01610.x; RA Feistritzer C., Lenta R., Riewald M.; RT "Protease-activated receptors-1 and -2 can mediate endothelial barrier RT protection: role in factor Xa signaling."; RL J. Thromb. Haemost. 3:2798-2805(2005). RN [28] RP POSSIBLE INVOLVEMENT IN COLITIS. RX PubMed=15919826; DOI=10.1073/pnas.0409535102; RA Hansen K.K., Sherman P.M., Cellars L., Andrade-Gordon P., Pan Z., RA Baruch A., Wallace J.L., Hollenberg M.D., Vergnolle N.; RT "A major role for proteolytic activity and proteinase-activated receptor-2 RT in the pathogenesis of infectious colitis."; RL Proc. Natl. Acad. Sci. U.S.A. 102:8363-8368(2005). RN [29] RP POSSIBLE INVOLVEMENT IN BRONCHIAL EOSINOPHILIC INFLAMMATION. RX PubMed=15879675; DOI=10.1254/jphs.scz050138; RA Takizawa T., Tamiya M., Hara T., Matsumoto J., Saito N., Kanke T., RA Kawagoe J., Hattori Y.; RT "Abrogation of bronchial eosinophilic inflammation and attenuated eotaxin RT content in protease-activated receptor 2-deficient mice."; RL J. Pharmacol. Sci. 98:99-102(2005). RN [30] RP FUNCTION IN EPITHELIAL BARRIER DISRUPTION. RX PubMed=16714334; DOI=10.1152/ajplung.00046.2006; RA Winter M.C., Shasby S.S., Ries D.R., Shasby D.M.; RT "PAR2 activation interrupts E-cadherin adhesion and compromises the airway RT epithelial barrier: protective effect of beta-agonists."; RL Am. J. Physiol. 291:L628-L635(2006). RN [31] RP FUNCTION, AND ACTIVATION BY PRTN3. RX PubMed=16478888; DOI=10.1182/blood-2005-05-1875; RA Csernok E., Ai M., Gross W.L., Wicklein D., Petersen A., Lindner B., RA Lamprecht P., Holle J.U., Hellmich B.; RT "Wegener autoantigen induces maturation of dendritic cells and licenses RT them for Th1 priming via the protease-activated receptor-2 pathway."; RL Blood 107:4440-4448(2006). RN [32] RP POSSIBLE INVOLVEMENT IN ENCEPHALOMYELITIS AND MULTIPLE SCLEROSIS. RX PubMed=16476770; DOI=10.1084/jem.20052148; RA Noorbakhsh F., Tsutsui S., Vergnolle N., Boven L.A., Shariat N., RA Vodjgani M., Warren K.G., Andrade-Gordon P., Hollenberg M.D., Power C.; RT "Proteinase-activated receptor 2 modulates neuroinflammation in RT experimental autoimmune encephalomyelitis and multiple sclerosis."; RL J. Exp. Med. 203:425-435(2006). RN [33] RP FUNCTION IN ACTIN FILAMENT SEVERING. RX PubMed=17500066; DOI=10.1074/jbc.m701391200; RA Zoudilova M., Kumar P., Ge L., Wang P., Bokoch G.M., DeFea K.A.; RT "Beta-arrestin-dependent regulation of the cofilin pathway downstream of RT protease-activated receptor-2."; RL J. Biol. Chem. 282:20634-20646(2007). RN [34] RP INTERACTION WITH TMED2. RX PubMed=17693410; DOI=10.1074/jbc.m703205200; RA Luo W., Wang Y., Reiser G.; RT "p24A, a type I transmembrane protein, controls ARF1-dependent RT resensitization of protease-activated receptor-2 by influence on receptor RT trafficking."; RL J. Biol. Chem. 282:30246-30255(2007). RN [35] RP FUNCTION, AND ACTIVATION BY MOLD ALLERGENS. RX PubMed=17404307; DOI=10.4049/jimmunol.178.8.5237; RA Chiu L.L., Perng D.W., Yu C.H., Su S.N., Chow L.P.; RT "Mold allergen, pen C 13, induces IL-8 expression in human airway RT epithelial cells by activating protease-activated receptor 1 and 2."; RL J. Immunol. 178:5237-5244(2007). RN [36] RP FUNCTION, AND ACTIVATION BY BACTERIAL CHITINASE. RX PubMed=18474671; DOI=10.1165/rcmb.2007-0410oc; RA Hong J.H., Hong J.Y., Park B., Lee S.I., Seo J.T., Kim K.E., Sohn M.H., RA Shin D.M.; RT "Chitinase activates protease-activated receptor-2 in human airway RT epithelial cells."; RL Am. J. Respir. Cell Mol. Biol. 39:530-535(2008). RN [37] RP FUNCTION. RX PubMed=18424071; DOI=10.1016/j.cellsig.2008.02.015; RA Goon Goh F., Sloss C.M., Cunningham M.R., Nilsson M., Cadalbert L., RA Plevin R.; RT "G-protein-dependent and -independent pathways regulate proteinase- RT activated receptor-2 mediated p65 NFkappaB serine 536 phosphorylation in RT human keratinocytes."; RL Cell. Signal. 20:1267-1274(2008). RN [38] RP FUNCTION, AND INTERACTION WITH TLR4. RX PubMed=18622013; DOI=10.1074/jbc.m804800200; RA Rallabhandi P., Nhu Q.M., Toshchakov V.Y., Piao W., Medvedev A.E., RA Hollenberg M.D., Fasano A., Vogel S.N.; RT "Analysis of proteinase-activated receptor 2 and TLR4 signal transduction: RT a novel paradigm for receptor cooperativity."; RL J. Biol. Chem. 283:24314-24325(2008). RN [39] RP FUNCTION IN ANTIVIRAL RESPONSE. RX PubMed=18453611; DOI=10.4049/jimmunol.180.10.6903; RA Feld M., Shpacovitch V.M., Ehrhardt C., Kerkhoff C., Hollenberg M.D., RA Vergnolle N., Ludwig S., Steinhoff M.; RT "Agonists of proteinase-activated receptor-2 enhance IFN-gamma-inducible RT effects on human monocytes: role in influenza A infection."; RL J. Immunol. 180:6903-6910(2008). RN [40] RP ACTIVITY REGULATION. RX PubMed=18434511; DOI=10.1523/jneurosci.0716-08.2008; RA Reddy V.B., Iuga A.O., Shimada S.G., LaMotte R.H., Lerner E.A.; RT "Cowhage-evoked itch is mediated by a novel cysteine protease: a ligand of RT protease-activated receptors."; RL J. Neurosci. 28:4331-4335(2008). RN [41] RP DEUBIQUITINATION. RX PubMed=19684015; DOI=10.1074/jbc.m109.025692; RA Hasdemir B., Murphy J.E., Cottrell G.S., Bunnett N.W.; RT "Endosomal deubiquitinating enzymes control ubiquitination and down- RT regulation of protease-activated receptor 2."; RL J. Biol. Chem. 284:28453-28466(2009). RN [42] RP PHOSPHORYLATION. RX PubMed=19815543; DOI=10.1074/jbc.m109.048942; RA Ricks T.K., Trejo J.; RT "Phosphorylation of protease-activated receptor-2 differentially regulates RT desensitization and internalization."; RL J. Biol. Chem. 284:34444-34457(2009). RN [43] RP FUNCTION IN ANTIVIRAL RESPONSE. RX PubMed=19494303; DOI=10.4049/jimmunol.0803743; RA Khoufache K., LeBouder F., Morello E., Laurent F., Riffault S., RA Andrade-Gordon P., Boullier S., Rousset P., Vergnolle N., Riteau B.; RT "Protective role for protease-activated receptor-2 against influenza virus RT pathogenesis via an IFN-gamma-dependent pathway."; RL J. Immunol. 182:7795-7802(2009). RN [44] RP FUNCTION, AND ACTIVATION BY TRYPSIN AND FUNGAL ASPARTATE PROTEASE. RX PubMed=19864598; DOI=10.4049/jimmunol.0901220; RA Matsuwaki Y., Wada K., White T.A., Benson L.M., Charlesworth M.C., RA Checkel J.L., Inoue Y., Hotta K., Ponikau J.U., Lawrence C.B., Kita H.; RT "Recognition of fungal protease activities induces cellular activation and RT eosinophil-derived neurotoxin release in human eosinophils."; RL J. Immunol. 183:6708-6716(2009). RN [45] RP POSSIBLE INVOLVEMENT IN ARTHRITIS. RX PubMed=20584806; DOI=10.1136/ard.2010.130336; RA Ferrell W.R., Kelso E.B., Lockhart J.C., Plevin R., McInnes I.B.; RT "Protease-activated receptor 2: a novel pathogenic pathway in a murine RT model of osteoarthritis."; RL Ann. Rheum. Dis. 69:2051-2054(2010). RN [46] RP FUNCTION IN JNK PATHWAY. RX PubMed=19781631; DOI=10.1016/j.cellsig.2009.09.028; RA McIntosh K., Cunningham M.R., Cadalbert L., Lockhart J., Boyd G., RA Ferrell W.R., Plevin R.; RT "Proteinase-activated receptor-2 mediated inhibition of TNFalpha-stimulated RT JNK activation - a novel paradigm for G(q/11) linked GPCRs."; RL Cell. Signal. 22:265-273(2010). RN [47] RP FUNCTION IN ENDOTHELIAL BARRIER PROTECTION. RX PubMed=20826780; DOI=10.1074/jbc.m110.163642; RA Bae J.S., Yang L., Rezaie A.R.; RT "Factor X/Xa elicits protective signaling responses in endothelial cells RT directly via PAR-2 and indirectly via endothelial protein C receptor- RT dependent recruitment of PAR-1."; RL J. Biol. Chem. 285:34803-34812(2010). RN [48] RP POSSIBLE INVOLVEMENT IN PERIODONTITIS. RX PubMed=20530726; DOI=10.1177/0022034510373765; RA Holzhausen M., Cortelli J.R., da Silva V.A., Franco G.C., Cortelli S.C., RA Vergnolle N.; RT "Protease-activated receptor-2 (PAR(2)) in human periodontitis."; RL J. Dent. Res. 89:948-953(2010). RN [49] RP FUNCTION. RX PubMed=19865078; DOI=10.1038/mi.2009.120; RA Nhu Q.M., Shirey K., Teijaro J.R., Farber D.L., Netzel-Arnett S., RA Antalis T.M., Fasano A., Vogel S.N.; RT "Novel signaling interactions between proteinase-activated receptor 2 and RT Toll-like receptors in vitro and in vivo."; RL Mucosal Immunol. 3:29-39(2010). RN [50] RP FUNCTION IN ANTIMICROBIAL RESPONSE. RX PubMed=21501162; DOI=10.1111/j.1365-2567.2011.03443.x; RA Shpacovitch V.M., Feld M., Holzinger D., Kido M., Hollenberg M.D., RA Levi-Schaffer F., Vergnolle N., Ludwig S., Roth J., Luger T., Steinhoff M.; RT "Role of proteinase-activated receptor-2 in anti-bacterial and RT immunomodulatory effects of interferon-gamma on human neutrophils and RT monocytes."; RL Immunology 133:329-339(2011). RN [51] RP PALMITOYLATION AT CYS-361. RX PubMed=21627585; DOI=10.1042/bj20101958; RA Botham A., Guo X., Xiao Y.P., Morice A.H., Compton S.J., Sadofsky L.R.; RT "Palmitoylation of human proteinase-activated receptor-2 differentially RT regulates receptor triggered ERK1/2 activation, calcium signalling, and RT endocytosis."; RL Biochem. J. 438:359-367(2011). RN [52] RP FUNCTION, TISSUE SPECIFICITY, AND PROTEOLYTIC CLEAVAGE. RX PubMed=23202369; DOI=10.1161/atvbaha.112.300474; RA Kuckleburg C.J., Newman P.J.; RT "Neutrophil proteinase 3 acts on protease-activated receptor-2 to enhance RT vascular endothelial cell barrier function."; RL Arterioscler. Thromb. Vasc. Biol. 33:275-284(2013). RN [53] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 59-269 AND 276-377, FUNCTION, RP DISULFIDE BOND, TOPOLOGY, AND MUTAGENESIS OF HIS-135; PHE-154; GLY-157; RP TYR-210; ASN-222; HIS-227; ASP-228 AND ILE-327. RX PubMed=28445455; DOI=10.1038/nature22309; RA Cheng R.K.Y., Fiez-Vandal C., Schlenker O., Edman K., Aggeler B., RA Brown D.G., Brown G.A., Cooke R.M., Dumelin C.E., Dore A.S., RA Geschwindner S., Grebner C., Hermansson N.O., Jazayeri A., Johansson P., RA Leong L., Prihandoko R., Rappas M., Soutter H., Snijder A., Sundstrom L., RA Tehan B., Thornton P., Troast D., Wiggin G., Zhukov A., Marshall F.H., RA Dekker N.; RT "Structural insight into allosteric modulation of protease-activated RT receptor 2."; RL Nature 545:112-115(2017). CC -!- FUNCTION: Receptor for trypsin and trypsin-like enzymes coupled to G CC proteins (PubMed:28445455). Its function is mediated through the CC activation of several signaling pathways including phospholipase C CC (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), CC I-kappaB kinase/NF-kappaB and Rho (PubMed:28445455). Can also be CC transactivated by cleaved F2R/PAR1. Involved in modulation of CC inflammatory responses and regulation of innate and adaptive immunity, CC and acts as a sensor for proteolytic enzymes generated during CC infection. Generally is promoting inflammation. Can signal CC synergistically with TLR4 and probably TLR2 in inflammatory responses CC and modulates TLR3 signaling. Has a protective role in establishing the CC endothelial barrier; the activity involves coagulation factor X. CC Regulates endothelial cell barrier integrity during neutrophil CC extravasation, probably following proteolytic cleavage by PRTN3 CC (PubMed:23202369). Proposed to have a bronchoprotective role in airway CC epithelium, but also shown to compromise the airway epithelial barrier CC by interrupting E-cadherin adhesion (PubMed:10086357). Involved in the CC regulation of vascular tone; activation results in hypotension CC presumably mediated by vasodilation. Associates with a subset of G CC proteins alpha subunits such as GNAQ, GNA11, GNA14, GNA12 and GNA13, CC but probably not with G(o)-alpha, G(i) subunit alpha-1 and G(i) subunit CC alpha-2. However, according to PubMed:21627585 can signal through G(i) CC subunit alpha. Believed to be a class B receptor which internalizes as CC a complex with arrestin and traffic with it to endosomal vesicles, CC presumably as desensitized receptor, for extended periods of time. CC Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via CC coupling to GNAQ and GNA11; the function involves dissociation of RIPK1 CC and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF- CC kappa-B RELA subunit at 'Ser-536'; the function involves IKBKB and is CC predominantly independent of G proteins. Involved in cellular CC migration. Involved in cytoskeletal rearrangement and chemotaxis CC through beta-arrestin-promoted scaffolds; the function is independent CC of GNAQ and GNA11 and involves promotion of cofilin dephosphorylation CC and actin filament severing. Induces redistribution of COPS5 from the CC plasma membrane to the cytosol and activation of the JNK cascade is CC mediated by COPS5. Involved in the recruitment of leukocytes to the CC sites of inflammation and is the major PAR receptor capable of CC modulating eosinophil function such as pro-inflammatory cytokine CC secretion, superoxide production and degranulation. During inflammation CC promotes dendritic cell maturation, trafficking to the lymph nodes and CC subsequent T-cell activation. Involved in antimicrobial response of CC innate immune cells; activation enhances phagocytosis of Gram-positive CC and killing of Gram-negative bacteria. Acts synergistically with CC interferon-gamma in enhancing antiviral responses. Implicated in a CC number of acute and chronic inflammatory diseases such as of the CC joints, lungs, brain, gastrointestinal tract, periodontium, skin, and CC vascular systems, and in autoimmune disorders. CC {ECO:0000269|PubMed:10086357, ECO:0000269|PubMed:10725339, CC ECO:0000269|PubMed:11413129, ECO:0000269|PubMed:11441110, CC ECO:0000269|PubMed:11447194, ECO:0000269|PubMed:11714832, CC ECO:0000269|PubMed:12832443, ECO:0000269|PubMed:15155775, CC ECO:0000269|PubMed:16359518, ECO:0000269|PubMed:16410250, CC ECO:0000269|PubMed:16478888, ECO:0000269|PubMed:16714334, CC ECO:0000269|PubMed:17404307, ECO:0000269|PubMed:17500066, CC ECO:0000269|PubMed:18424071, ECO:0000269|PubMed:18453611, CC ECO:0000269|PubMed:18474671, ECO:0000269|PubMed:18622013, CC ECO:0000269|PubMed:19494303, ECO:0000269|PubMed:19781631, CC ECO:0000269|PubMed:19864598, ECO:0000269|PubMed:19865078, CC ECO:0000269|PubMed:20826780, ECO:0000269|PubMed:21501162, CC ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:28445455}. CC -!- ACTIVITY REGULATION: Activated upon interaction by mucunain, a cowhage CC (Mucuna pruriens) plant cysteine proteinase. CC {ECO:0000269|PubMed:18434511}. CC -!- SUBUNIT: Interacts with TLR4, COPS5 and TMED2. Interacts with GNAQ, CC GNA11, GNA12, GNA13 and GNA14 (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC P55085; P16615: ATP2A2; NbExp=2; IntAct=EBI-4303189, EBI-358933; CC P55085; P22681: CBL; NbExp=3; IntAct=EBI-4303189, EBI-518228; CC P55085; Q92905: COPS5; NbExp=8; IntAct=EBI-4303189, EBI-594661; CC P55085; Q14868: EPR-1; NbExp=4; IntAct=EBI-4303189, EBI-4309771; CC P55085; P13726: F3; NbExp=2; IntAct=EBI-4303189, EBI-1040727; CC P55085; P0DMV9: HSPA1B; NbExp=2; IntAct=EBI-4303189, EBI-14100688; CC P55085; P04156: PRNP; NbExp=3; IntAct=EBI-4303189, EBI-977302; CC P55085; Q15363: TMED2; NbExp=6; IntAct=EBI-4303189, EBI-998485; CC P55085; P29066: Arrb1; Xeno; NbExp=6; IntAct=EBI-4303189, EBI-4303019; CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC -!- TISSUE SPECIFICITY: Widely expressed in tissues with especially high CC levels in pancreas, liver, kidney, small intestine, and colon CC (PubMed:7556175, PubMed:8615752). Moderate expression is detected in CC many organs, but none in brain or skeletal muscle (PubMed:7556175, CC PubMed:8615752). Expressed in endothelial cells (PubMed:23202369). CC {ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:7556175, CC ECO:0000269|PubMed:8615752}. CC -!- PTM: A proteolytic cleavage generates a new N-terminus that functions CC as a tethered ligand (PubMed:10831593, PubMed:19864598, PubMed:9020112, CC PubMed:10805786, PubMed:16478888). Activating serine proteases include CC trypsin, mast cell tryptase, coagulation factors VII and Xa, CC myeloblastin/PRTN3 and membrane-type serine protease 1/ST14 CC (PubMed:10831593, PubMed:19864598, PubMed:9020112, PubMed:10805786, CC PubMed:16478888, PubMed:23202369). Subsequent cleavage by serine CC proteases, including neutrophil elastase and cathepsin G, leads to CC receptor deactivation (PubMed:12594060). At least in part, implicated CC proteases are also shown to activate the receptor; the glycosylation CC status of the receptor is thought to contribute to the difference CC (PubMed:12171601). In addition to conventional trypsin-like proteases CC activated by other proteases and glycosidases derived from bacteria, CC fungi and insects (PubMed:11447194, PubMed:11441110, PubMed:17404307, CC PubMed:18474671, PubMed:19864598). Activated by serine protease CC allergens such as dust mite Der p3 and Der p9 and mold Pen c13 CC (PubMed:11441110, PubMed:17404307). Activated by P.gingivalis arginine- CC specific (trypsin-like) cysteine proteinases called gingipains CC (PubMed:11447194). Activated by S.griseus exogenous chitinase CC (PubMed:18474671). Activated by A.alternata aspartate protease; the CC cleavage generates non-conventional processed forms (PubMed:19864598). CC {ECO:0000269|PubMed:10805786, ECO:0000269|PubMed:10831593, CC ECO:0000269|PubMed:11441110, ECO:0000269|PubMed:11447194, CC ECO:0000269|PubMed:12171601, ECO:0000269|PubMed:12594060, CC ECO:0000269|PubMed:16478888, ECO:0000269|PubMed:17404307, CC ECO:0000269|PubMed:18474671, ECO:0000269|PubMed:19864598, CC ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:9020112}. CC -!- PTM: N-glycosylated and sialylated. {ECO:0000269|PubMed:12171601}. CC -!- PTM: Multiple phosphorylated on serine and threonine residues in the CC cytoplasmic region upon receptor activation; required for receptor CC desensitization and recruitment of beta-arrestin. CC {ECO:0000269|PubMed:19815543}. CC -!- PTM: Monoubiquitinated by CBL at the plasma membrane and in early CC endosomes; not required for receptor endocytosis but for translocation CC to late endosomes or lysosomes. Deubiquitination involves STAMBP and CC USP8; required for lysosomal trafficking and receptor degradation. CC -!- MISCELLANEOUS: Synthetic PAR agonist peptides (APs) that mimic the CC first six amino acids of the newly formed N-terminus activate the CC native, uncleaved receptor nonenzymatically by binding directly to the CC corresponding second extracellular loop to mediate signaling. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Protease-activated receptor entry; CC URL="https://en.wikipedia.org/wiki/Protease-activated_receptor"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/f2rl1/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z49993; CAA90290.1; -; Genomic_DNA. DR EMBL; Z49994; CAA90290.1; JOINED; Genomic_DNA. DR EMBL; U34038; AAB47871.1; -; mRNA. DR EMBL; AY336105; AAP97012.1; -; mRNA. DR EMBL; AF400075; AAK77914.1; -; Genomic_DNA. DR EMBL; BT009856; AAP88858.1; -; mRNA. DR EMBL; CH471084; EAW95782.1; -; Genomic_DNA. DR EMBL; BC012453; AAH12453.1; -; mRNA. DR EMBL; BC018130; AAH18130.1; -; mRNA. DR EMBL; U36753; AAA90957.1; -; Genomic_DNA. DR CCDS; CCDS4033.1; -. DR PIR; S66518; S66518. DR RefSeq; NP_005233.3; NM_005242.5. DR PDB; 5NDD; X-ray; 2.80 A; A=59-269, A=276-377. DR PDB; 5NDZ; X-ray; 3.60 A; A=59-269, A=276-377. DR PDB; 5NJ6; X-ray; 4.00 A; A=55-269, A=276-377. DR PDBsum; 5NDD; -. DR PDBsum; 5NDZ; -. DR PDBsum; 5NJ6; -. DR AlphaFoldDB; P55085; -. DR SMR; P55085; -. DR BioGRID; 108449; 204. DR DIP; DIP-42044N; -. DR IntAct; P55085; 77. DR MINT; P55085; -. DR STRING; 9606.ENSP00000296677; -. DR BindingDB; P55085; -. DR ChEMBL; CHEMBL5963; -. DR GuidetoPHARMACOLOGY; 348; -. DR TCDB; 9.A.14.13.12; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P55085; 2 sites, No reported glycans. DR GlyGen; P55085; 7 sites, 1 O-linked glycan (5 sites). DR iPTMnet; P55085; -. DR PhosphoSitePlus; P55085; -. DR SwissPalm; P55085; -. DR BioMuta; F2RL1; -. DR DMDM; 1709580; -. DR jPOST; P55085; -. DR MassIVE; P55085; -. DR MaxQB; P55085; -. DR PaxDb; 9606-ENSP00000296677; -. DR PeptideAtlas; P55085; -. DR ProteomicsDB; 56787; -. DR ABCD; P55085; 81 sequenced antibodies. DR Antibodypedia; 4569; 382 antibodies from 36 providers. DR DNASU; 2150; -. DR Ensembl; ENST00000296677.5; ENSP00000296677.4; ENSG00000164251.5. DR GeneID; 2150; -. DR KEGG; hsa:2150; -. DR MANE-Select; ENST00000296677.5; ENSP00000296677.4; NM_005242.6; NP_005233.4. DR UCSC; uc003keo.4; human. DR AGR; HGNC:3538; -. DR CTD; 2150; -. DR DisGeNET; 2150; -. DR GeneCards; F2RL1; -. DR HGNC; HGNC:3538; F2RL1. DR HPA; ENSG00000164251; Tissue enhanced (intestine, stomach). DR MIM; 600933; gene. DR neXtProt; NX_P55085; -. DR PharmGKB; PA27947; -. DR VEuPathDB; HostDB:ENSG00000164251; -. DR eggNOG; ENOG502QR8S; Eukaryota. DR HOGENOM; CLU_009579_8_2_1; -. DR InParanoid; P55085; -. DR OrthoDB; 4075920at2759; -. DR PhylomeDB; P55085; -. DR TreeFam; TF330775; -. DR PathwayCommons; P55085; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; P55085; -. DR SIGNOR; P55085; -. DR BioGRID-ORCS; 2150; 13 hits in 1164 CRISPR screens. DR ChiTaRS; F2RL1; human. DR GeneWiki; Protease_activated_receptor_2; -. DR GenomeRNAi; 2150; -. DR Pharos; P55085; Tchem. DR PRO; PR:P55085; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P55085; Protein. DR Bgee; ENSG00000164251; Expressed in mucosa of sigmoid colon and 153 other cell types or tissues. DR ExpressionAtlas; P55085; baseline and differential. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0031143; C:pseudopodium; ISS:UniProtKB. DR GO; GO:0004930; F:G protein-coupled receptor activity; IMP:UniProtKB. DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB. DR GO; GO:0031681; F:G-protein beta-subunit binding; ISS:UniProtKB. DR GO; GO:0002020; F:protease binding; IPI:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0015057; F:thrombin-activated receptor activity; IEA:InterPro. DR GO; GO:0007596; P:blood coagulation; IEA:InterPro. DR GO; GO:0045217; P:cell-cell junction maintenance; IMP:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB. DR GO; GO:0061028; P:establishment of endothelial barrier; IDA:UniProtKB. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0050900; P:leukocyte migration; IDA:UniProtKB. DR GO; GO:0070661; P:leukocyte proliferation; ISS:UniProtKB. DR GO; GO:0097029; P:mature conventional dendritic cell differentiation; IDA:UniProtKB. DR GO; GO:0032682; P:negative regulation of chemokine production; IDA:UniProtKB. DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0046329; P:negative regulation of JNK cascade; IDA:UniProtKB. DR GO; GO:0034140; P:negative regulation of toll-like receptor 3 signaling pathway; IMP:UniProtKB. DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0042119; P:neutrophil activation; IDA:UniProtKB. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0030836; P:positive regulation of actin filament depolymerization; IDA:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB. DR GO; GO:0032722; P:positive regulation of chemokine production; IDA:UniProtKB. DR GO; GO:0050921; P:positive regulation of chemotaxis; ISS:UniProtKB. DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; IDA:UniProtKB. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB. DR GO; GO:0043311; P:positive regulation of eosinophil degranulation; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0003104; P:positive regulation of glomerular filtration; ISS:UniProtKB. DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:UniProtKB. DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB. DR GO; GO:0002690; P:positive regulation of leukocyte chemotaxis; IDA:BHF-UCL. DR GO; GO:0070963; P:positive regulation of neutrophil mediated killing of gram-negative bacterium; IDA:UniProtKB. DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; IDA:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0050927; P:positive regulation of positive chemotaxis; IDA:BHF-UCL. DR GO; GO:0031274; P:positive regulation of pseudopodium assembly; ISS:UniProtKB. DR GO; GO:1900135; P:positive regulation of renin secretion into blood stream; ISS:UniProtKB. DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IMP:UniProtKB. DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IDA:UniProtKB. DR GO; GO:0034137; P:positive regulation of toll-like receptor 2 signaling pathway; IMP:UniProtKB. DR GO; GO:0034141; P:positive regulation of toll-like receptor 3 signaling pathway; IMP:UniProtKB. DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0032729; P:positive regulation of type II interferon production; ISS:UniProtKB. DR GO; GO:0099109; P:potassium channel activating, G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0030193; P:regulation of blood coagulation; IDA:BHF-UCL. DR GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:2000341; P:regulation of chemokine (C-X-C motif) ligand 2 production; IDA:UniProtKB. DR GO; GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB. DR GO; GO:0002286; P:T cell activation involved in immune response; ISS:UniProtKB. DR GO; GO:0042311; P:vasodilation; ISS:UniProtKB. DR CDD; cd15370; 7tmA_PAR2; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR002281; Pro_rcpt_2. DR InterPro; IPR003912; Protea_act_rcpt. DR PANTHER; PTHR24232; G-PROTEIN COUPLED RECEPTOR; 1. DR PANTHER; PTHR24232:SF21; PROTEINASE-ACTIVATED RECEPTOR 2; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR01428; PROTEASEAR. DR PRINTS; PR01152; PROTEASEAR2. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P55085; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor; KW Glycoprotein; Immunity; Inflammatory response; Innate immunity; KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT PROPEP 26..36 FT /note="Removed for receptor activation" FT /id="PRO_0000012750" FT CHAIN 37..397 FT /note="Proteinase-activated receptor 2" FT /id="PRO_0000412954" FT CHAIN 38..397 FT /note="Proteinase-activated receptor 2, alternate cleaved FT 1" FT /id="PRO_0000412956" FT CHAIN 39..397 FT /note="Proteinase-activated receptor 2, alternate cleaved FT 2" FT /id="PRO_0000012751" FT TOPO_DOM 37..71 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:28445455" FT TRANSMEM 72..101 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:28445455" FT TOPO_DOM 102..108 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:28445455" FT TRANSMEM 109..137 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:28445455" FT TOPO_DOM 138..149 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:28445455" FT TRANSMEM 150..177 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:28445455" FT TOPO_DOM 178..183 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:28445455" FT TRANSMEM 184..211 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:28445455" FT TOPO_DOM 212..235 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:28445455" FT TRANSMEM 236..269 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:28445455" FT TOPO_DOM 270..277 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:28445455" FT TRANSMEM 278..317 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:28445455" FT TOPO_DOM 318..323 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:28445455" FT TRANSMEM 324..347 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:28445455" FT TOPO_DOM 348..397 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:28445455" FT REGION 373..397 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 36..37 FT /note="Cleavage; by trypsin" FT LIPID 361 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:21627585" FT CARBOHYD 30 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12171601" FT CARBOHYD 222 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12171601" FT DISULFID 148..226 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521, FT ECO:0000269|PubMed:28445455, ECO:0007744|PDB:5NDD, FT ECO:0007744|PDB:5NDZ, ECO:0007744|PDB:5NJ6" FT VARIANT 21 FT /note="S -> F (in dbSNP:rs2243072)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_012846" FT VARIANT 30 FT /note="N -> S (in dbSNP:rs616235)" FT /id="VAR_049435" FT VARIANT 270 FT /note="R -> Q (in dbSNP:rs2243062)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_012847" FT VARIANT 291 FT /note="T -> A (in dbSNP:rs2243083)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_012848" FT MUTAGEN 30 FT /note="N->A: Decreases cell surface expression; when FT associate with A-222." FT /evidence="ECO:0000269|PubMed:12171601" FT MUTAGEN 30 FT /note="N->A: Increase of sensitivity towards tryptase." FT /evidence="ECO:0000269|PubMed:12171601" FT MUTAGEN 135 FT /note="H->Y: Slight reduction in ligand-mediated receptor FT activation." FT /evidence="ECO:0000269|PubMed:28445455" FT MUTAGEN 154 FT /note="F->A: Severe reduction in ligand-mediated receptor FT activation." FT /evidence="ECO:0000269|PubMed:28445455" FT MUTAGEN 157 FT /note="G->C,M: Severe reduction in ligand-mediated receptor FT activation." FT /evidence="ECO:0000269|PubMed:28445455" FT MUTAGEN 210 FT /note="Y->L: No defect in ligand-mediated receptor FT activation." FT /evidence="ECO:0000269|PubMed:28445455" FT MUTAGEN 222 FT /note="N->A: Decreases cell surface expression; when FT associated with A-30. Loss of sensitivity towards all FT tested proteases." FT /evidence="ECO:0000269|PubMed:12171601" FT MUTAGEN 222 FT /note="N->Q: No defect in ligand-mediated receptor FT activation." FT /evidence="ECO:0000269|PubMed:28445455" FT MUTAGEN 227 FT /note="H->A: No defect in ligand-mediated receptor FT activation." FT /evidence="ECO:0000269|PubMed:28445455" FT MUTAGEN 227 FT /note="H->Q: Slight reduction in ligand-mediated receptor FT activation." FT /evidence="ECO:0000269|PubMed:28445455" FT MUTAGEN 228 FT /note="D->A,N: Severe reduction in ligand-mediated receptor FT activation." FT /evidence="ECO:0000269|PubMed:28445455" FT MUTAGEN 327 FT /note="I->L: Slight reduction in ligand-mediated receptor FT activation." FT /evidence="ECO:0000269|PubMed:28445455" FT MUTAGEN 355..363 FT /note="Missing: Abolishes signaling through accumulation of FT intracellular calcium and phosphoinositide; no effect in FT signaling through MAPK." FT /evidence="ECO:0000269|PubMed:14607272" FT MUTAGEN 361 FT /note="C->A: Loss of palmitoylation; increases surface FT expression and internalization following trypsin FT activation, decreases sensitivity and intracellular calcium FT signaling, increases ERK activation through G(i) subunit FT alpha." FT MUTAGEN 363 FT /note="S->A: Reduces receptor desensitization and FT internalization, activates ERK1/2; when associated with FT A-366." FT /evidence="ECO:0000269|PubMed:10725339" FT MUTAGEN 366 FT /note="T->A: Reduces receptor desensitization and FT internalization, activates ERK1/2; when associated with FT A-363." FT /evidence="ECO:0000269|PubMed:10725339" FT CONFLICT 138 FT /note="G -> A (in Ref. 2; AAB47871)" FT /evidence="ECO:0000305" FT CONFLICT 291 FT /note="T -> S (in Ref. 7; AAH18130)" FT /evidence="ECO:0000305" FT HELIX 63..68 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 72..75 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 77..102 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 109..125 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 128..136 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 145..178 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 186..205 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 207..210 FT /evidence="ECO:0007829|PDB:5NDD" FT STRAND 215..218 FT /evidence="ECO:0007829|PDB:5NDD" FT TURN 219..222 FT /evidence="ECO:0007829|PDB:5NDD" FT STRAND 223..229 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 233..235 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 236..249 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 252..269 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 279..298 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 301..316 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 323..332 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 333..335 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 336..347 FT /evidence="ECO:0007829|PDB:5NDD" FT HELIX 349..358 FT /evidence="ECO:0007829|PDB:5NDD" SQ SEQUENCE 397 AA; 44126 MW; F1A4E1D5AB9B362B CRC64; MRSPSAAWLL GAAILLAASL SCSGTIQGTN RSSKGRSLIG KVDGTSHVTG KGVTVETVFS VDEFSASVLT GKLTTVFLPI VYTIVFVVGL PSNGMALWVF LFRTKKKHPA VIYMANLALA DLLSVIWFPL KIAYHIHGNN WIYGEALCNV LIGFFYGNMY CSILFMTCLS VQRYWVIVNP MGHSRKKANI AIGISLAIWL LILLVTIPLY VVKQTIFIPA LNITTCHDVL PEQLLVGDMF NYFLSLAIGV FLFPAFLTAS AYVLMIRMLR SSAMDENSEK KRKRAIKLIV TVLAMYLICF TPSNLLLVVH YFLIKSQGQS HVYALYIVAL CLSTLNSCID PFVYYFVSHD FRDHAKNALL CRSVRTVKQM QVSLTSKKHS RKSSSYSSSS TTVKTSY //