PAR2_HUMAN
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 03-AUG-2022, entry version 198.
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 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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 -!- 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/";
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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; 203.
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 GlyGen; P55085; 2 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; P55085; -.
DR PeptideAtlas; P55085; -.
DR PRIDE; P55085; -.
DR ProteomicsDB; 56787; -.
DR ABCD; P55085; 81 sequenced antibodies.
DR Antibodypedia; 4569; 312 antibodies from 36 providers.
DR DNASU; 2150; -.
DR Ensembl; ENST00000296677.5; ENSP00000296677.4; ENSG00000164251.5.
DR GeneID; 2150; -.
DR KEGG; hsa:2150; -.
DR UCSC; uc003keo.4; human.
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; 892946at2759; -.
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; 12 hits in 1086 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 151 other tissues.
DR ExpressionAtlas; P55085; baseline and differential.
DR Genevisible; P55085; HS.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
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: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: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:0030836; P:positive regulation of actin filament depolymerization; 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:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; IBA:GO_Central.
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:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS: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:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; 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:0030193; P:regulation of blood coagulation; IDA:BHF-UCL.
DR GO; GO:2000341; P:regulation of chemokine (C-X-C motif) ligand 2 production; IDA:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; 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 InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR002281; Pro_rcpt_2.
DR InterPro; IPR003912; Protea_act_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01428; PROTEASEAR.
DR PRINTS; PR01152; PROTEASEAR2.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
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 A-
FT 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 A-
FT 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
