P55085 (PAR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proteinase-activated receptor 2
Short name=PAR-2

Alternative name(s):
Coagulation factor II receptor-like 1
G-protein coupled receptor 11
Thrombin receptor-like 1

Cleaved into the following 2 chains:

1. Proteinase-activated receptor 2, alternate cleaved 1
2. Proteinase-activated receptor 2, alternate cleaved 2

Gene names

Name:	F2RL1
Synonyms:	GPR11, PAR2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	397 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion. Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilatation. Associates with a subset of G proteins alpha subunits such as G alpha-q, G alpha-11, G alpha-14, G alpha-12 and G alpha-13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. However, according to Ref.49 can signal through G(i) subunit alpha. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via coupling to G alpha-q/11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of G alpha-q/11 and involves promotion of cofilin dephosphoryltaion and actin filament severing. Induces redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor capable of modulating eosinophil function such as proinflammatory cytokine secretion, superoxide production and degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and subsequent T-cell activation. Involved in antimicrobial response of innate immnune cells; activation enhances phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma in enhancing antiviral responses. Implicated in a number of acute and chronic inflammatory diseases such as of the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune disorders. Ref.7 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15 Ref.20 Ref.22 Ref.24 Ref.27 Ref.28 Ref.29 Ref.31 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.41 Ref.42 Ref.44 Ref.45 Ref.47 Ref.48
Subunit structure	Interacts with TLR4, COPS5 and TMED2. Interacts with GNAQ, GNA11, GNA12, GNA13 and GNA14 By similarity. Ref.29 Ref.32 Ref.36
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Widely expressed in tissues with especially high levels in pancreas, liver, kidney, small intestine, and colon. Moderate expression is detected in many organs, but none in brain or skeletal muscle.
Post-translational modification	A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand. Activating serine proteases include trypsin, mast cell tryptase, coagulation factors VII and Xa, myeloblastin/PRTN3 and membrane-type serine protease 1/ST14. Proposed subsequent cleaveage by serine proteases is leading to receptor deactivation and include neutrophil elastase and cathepsin G. At least in part, implicated proteases are also shown to activate the receptor; the glycosylation status of the receptor is thought to contribute to the difference. In addition to conventional trypsin-like proteases is proposed to be activated by other proteases and glycosidases derived from bacteria, fungi and insects: serine protease allergens such as dust mite Der p3 and Der p9 and mold Pen c13, Porphyromonas gingivalis arginine-specific (trypsin-like) cysteine proteinases called gingipains, Streptomyces griseus exogenous chitinase, and an Alternaria alternata aspartate protease. Cleavage by the Alternaria alternata aspartate protease generates non-conventional processed forms. N-glycosylated and sialylated. Ref.16 Multiple phosphorylated on serine and threonine residues in the cytoplasmic region upon receptor activation; required for receptor desensitization and recruitment of beta-arrestin. Ref.38 Ref.40 Monoubiquitinated by CBL at the plasma membrane and in early endosomes; not required for receptor endocytosis but for translocation to late endosomes or lysosomes. Deubiquitination involves STAMBP and USP8; required for lysosomal trafficking and receptor degradation.
Miscellaneous	Synthetic PAR agonist peptides (APs) that mimic the first six amino acids of the newly formed N-terminus activate the native, uncleaved receptor nonenzymatically by binding directly to the corresponding second extracellular loop to mediate signaling.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Biological process	Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	T cell activation involved in immune response Inferred from sequence or structural similarity. Source: UniProtKB blood coagulation Inferred from electronic annotation. Source: InterPro chemokine (C-C motif) ligand 2 secretion Inferred from direct assay Ref.48. Source: UniProtKB defense response to virus Inferred from direct assay Ref.37Ref.41. Source: UniProtKB elevation of cytosolic calcium ion concentration Inferred from direct assay Ref.9. Source: UniProtKB establishment of endothelial barrier Inferred from direct assay Ref.45. Source: UniProtKB inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW interleukin-1 beta secretion Inferred from direct assay Ref.22. Source: UniProtKB interleukin-10 secretion Inferred from direct assay Ref.37. Source: UniProtKB leukocyte migration Inferred from direct assay Ref.22. Source: UniProtKB mature dendritic cell differentiation Inferred from direct assay Ref.28. Source: UniProtKB negative regulation of JNK cascade Inferred from direct assay Ref.44. Source: UniProtKB negative regulation of chemokine secretion Inferred from direct assay Ref.47. Source: UniProtKB negative regulation of toll-like receptor 3 signaling pathway Inferred from mutant phenotype Ref.47. Source: UniProtKB negative regulation of tumor necrosis factor-mediated signaling pathway Inferred from direct assay Ref.44. Source: UniProtKB neutrophil activation Inferred from direct assay Ref.22. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from direct assay Ref.9. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay Ref.13. Source: UniProtKB positive regulation of JNK cascade Inferred from direct assay Ref.13. Source: UniProtKB positive regulation of Rho protein signal transduction Inferred from mutant phenotype Ref.45. Source: UniProtKB positive regulation of actin filament depolymerization Inferred from direct assay Ref.31. Source: UniProtKB positive regulation of cytokine secretion involved in immune response Inferred from direct assay Ref.14. Source: UniProtKB positive regulation of eosinophil degranulation Inferred from direct assay Ref.15. Source: UniProtKB positive regulation of interleukin-6 secretion Inferred from direct assay Ref.12Ref.22. Source: UniProtKB positive regulation of interleukin-8 secretion Inferred from direct assay Ref.22Ref.33Ref.36Ref.47. Source: UniProtKB positive regulation of leukocyte chemotaxis Inferred from direct assay. Source: BHF-UCL positive regulation of neutrophil mediated killing of gram-negative bacterium Inferred from direct assay Ref.48. Source: UniProtKB positive regulation of phagocytosis, engulfment Inferred from direct assay Ref.48. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of positive chemotaxis Inferred from direct assay. Source: BHF-UCL positive regulation of pseudopodium assembly Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of superoxide anion generation Inferred from direct assay Ref.15. Source: UniProtKB positive regulation of toll-like receptor 2 signaling pathway Inferred from mutant phenotype Ref.47. Source: UniProtKB positive regulation of toll-like receptor 3 signaling pathway Inferred from mutant phenotype Ref.47. Source: UniProtKB positive regulation of toll-like receptor 4 signaling pathway Inferred from direct assay Ref.36. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.29. Source: UniProtKB positive regulation of vasodilation Inferred from sequence or structural similarity. Source: UniProtKB regulation of blood coagulation Inferred from direct assay. Source: BHF-UCL
Cellular component	Golgi apparatus Traceable author statement. Source: ProtInc integral to plasma membrane Inferred from direct assay. Source: BHF-UCL pseudopodium Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	G-protein alpha-subunit binding Inferred from sequence or structural similarity. Source: UniProtKB G-protein beta-subunit binding Inferred from sequence or structural similarity. Source: UniProtKB receptor binding Traceable author statement. Source: ProtInc thrombin receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CBL	P22681	3	EBI-4303189,EBI-518228
COPS5	Q92905	8	EBI-4303189,EBI-594661
EPR1	Q14868	4	EBI-4303189,EBI-4309771
TMED2	Q15363	5	EBI-4303189,EBI-998485

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Propeptide	26 – 38	13	Removed for receptor activation, alternate 2		PRO_0000412957
	Propeptide	26 – 37	12	Removed for receptor activation, alternate 1		PRO_0000412955
	Propeptide	26 – 36	11	Removed for receptor activation		PRO_0000012750
	Chain	37 – 397	361	Proteinase-activated receptor 2		PRO_0000412954
	Chain	38 – 397	360	Proteinase-activated receptor 2, alternate cleaved 1		PRO_0000412956
	Chain	39 – 397	359	Proteinase-activated receptor 2, alternate cleaved 2		PRO_0000012751
Regions
	Topological domain	37 – 75	39	Extracellular Potential
	Transmembrane	76 – 101	26	Helical; Name=1; Potential
	Topological domain	102 – 110	9	Cytoplasmic Potential
	Transmembrane	111 – 130	20	Helical; Name=2; Potential
	Topological domain	131 – 149	19	Extracellular Potential
	Transmembrane	150 – 171	22	Helical; Name=3; Potential
	Topological domain	172 – 190	19	Cytoplasmic Potential
	Transmembrane	191 – 211	21	Helical; Name=4; Potential
	Topological domain	212 – 241	30	Extracellular Potential
	Transmembrane	242 – 260	19	Helical; Name=5; Potential
	Topological domain	261 – 285	25	Cytoplasmic Potential
	Transmembrane	286 – 308	23	Helical; Name=6; Potential
	Topological domain	309 – 323	15	Extracellular Potential
	Transmembrane	324 – 347	24	Helical; Name=7; Potential
	Topological domain	348 – 397	50	Cytoplasmic Potential
	Compositional bias	383 – 390	8	Poly-Ser
Sites
	Site	36 – 37	2	Cleavage; by trypsin
Amino acid modifications
	Modified residue	373	1	Phosphoserine Ref.38
	Lipidation	361	1	S-palmitoyl cysteine Ref.49
	Glycosylation	30	1	N-linked (GlcNAc...) Ref.16
	Glycosylation	222	1	N-linked (GlcNAc...) Ref.16
	Disulfide bond	148 ↔ 226		By similarity
Natural variations
	Natural variant	21	1	S → F. Ref.3 Corresponds to variant rs2243072 [ dbSNP | Ensembl ].		VAR_012846
	Natural variant	30	1	N → S. Corresponds to variant rs616235 [ dbSNP | Ensembl ].		VAR_049435
	Natural variant	270	1	R → Q. Ref.3 Corresponds to variant rs2243062 [ dbSNP | Ensembl ].		VAR_012847
	Natural variant	291	1	T → A. Ref.3 Corresponds to variant rs2243083 [ dbSNP | Ensembl ].		VAR_012848
Experimental info
	Mutagenesis	30	1	N → A: Decreases cell surface expression; when associate with A-222. Ref.16
	Mutagenesis	30	1	N → A: Increase of sensitivity towards tryptase. Ref.16
	Mutagenesis	222	1	N → A: Decreases cell surface expression; when associate with A-30. Ref.16
	Mutagenesis	222	1	N → A: Loss of sensitivity towards all tested proteases. Ref.16
	Mutagenesis	355 – 363	9	Missing: Abolishes signaling through accumulation of intracellular calcium and phosphoinositide; no effect in signaling through MAPK. Ref.9 Ref.21
	Mutagenesis	361	1	C → A: Loss of palmitoylation; increases surface expression and internalization following trypsin activation, decreases sensitivity and intracellular calcium signaling, increases ERK activation through G(i) subunit alpha.
	Mutagenesis	363	1	S → A: Reduces receptor desensitization and internalization, activates ERK1/2; when associated with A-366. Ref.9
	Mutagenesis	366	1	T → A: Reduces receptor desensitization and internalization, activates ERK1/2; when associated with A-363. Ref.9
	Sequence conflict	138	1	G → A in AAB47871. Ref.2
	Sequence conflict	291	1	T → S in AAH18130. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P55085 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: F1A4E1D5AB9B362B	FASTA	397	44,126
	10 20 30 40 50 60 MRSPSAAWLL GAAILLAASL SCSGTIQGTN RSSKGRSLIG KVDGTSHVTG KGVTVETVFS 70 80 90 100 110 120 VDEFSASVLT GKLTTVFLPI VYTIVFVVGL PSNGMALWVF LFRTKKKHPA VIYMANLALA 130 140 150 160 170 180 DLLSVIWFPL KIAYHIHGNN WIYGEALCNV LIGFFYGNMY CSILFMTCLS VQRYWVIVNP 190 200 210 220 230 240 MGHSRKKANI AIGISLAIWL LILLVTIPLY VVKQTIFIPA LNITTCHDVL PEQLLVGDMF 250 260 270 280 290 300 NYFLSLAIGV FLFPAFLTAS AYVLMIRMLR SSAMDENSEK KRKRAIKLIV TVLAMYLICF 310 320 330 340 350 360 TPSNLLLVVH YFLIKSQGQS HVYALYIVAL CLSTLNSCID PFVYYFVSHD FRDHAKNALL 370 380 390 CRSVRTVKQM QVSLTSKKHS RKSSSYSSSS TTVKTSY

References

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[1]	"Molecular cloning and functional expression of the gene encoding the human proteinase-activated receptor 2." Nystedt S., Emilsson K., Larsson A.-K., Stroembeck B., Sundelin J. Eur. J. Biochem. 232:84-89(1995) [PubMed: 7556175] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2." Boehm S.K., Kong W., Broemme D., Smeekens S.P., Anderson D.C., Connolly A.J., Kahn M.L., Nelken N.A., Coughlin S.R., Payan D.G., Bunnett N.W. Biochem. J. 314:1009-1016(1996) [PubMed: 8615752] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[3]	SeattleSNPs variation discovery resource Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PHE-21; GLN-270 AND ALA-291.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary and Pancreas.
[5]	"Conserved structure and adjacent location of the thrombin receptor and protease-activated receptor 2 genes define a protease-activated receptor gene cluster." Kahn M.L., Ishii K., Kuo W.L., Piper M., Connolly A.J., Shi Y.P., Wu R., Lin C.C., Coughlin S.R. Mol. Med. 2:349-357(1996) [PubMed: 8784787] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-397.
[6]	"Interactions of mast cell tryptase with thrombin receptors and PAR-2." Molino M., Barnathan E.S., Numerof R., Clark J., Dreyer M., Cumashi A., Hoxie J.A., Schechter N., Woolkalis M., Brass L.F. J. Biol. Chem. 272:4043-4049(1997) [PubMed: 9020112] [Abstract] Cited for: ACTIVATION BY MAST CELL TRYPTASE.
[7]	"A protective role for protease-activated receptors in the airways." Cocks T.M., Fong B., Chow J.M., Anderson G.P., Frauman A.G., Goldie R.G., Henry P.J., Carr M.J., Hamilton J.R., Moffatt J.D. Nature 398:156-160(1999) [PubMed: 10086357] [Abstract] Cited for: FUNCTION IN EPITHELIAL BARRIER PROTECTION.
[8]	"Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1." O'Brien P.J., Prevost N., Molino M., Hollinger M.K., Woolkalis M.J., Woulfe D.S., Brass L.F. J. Biol. Chem. 275:13502-13509(2000) [PubMed: 10788464] [Abstract] Cited for: TRANSACTIVATION BY F2R.
[9]	"beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2." DeFea K.A., Zalevsky J., Thoma M.S., Dery O., Mullins R.D., Bunnett N.W. J. Cell Biol. 148:1267-1281(2000) [PubMed: 10725339] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF SER-363 AND THR-366.
[10]	"Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates." Takeuchi T., Harris J.L., Huang W., Yan K.W., Coughlin S.R., Craik C.S. J. Biol. Chem. 275:26333-26342(2000) [PubMed: 10831593] [Abstract] Cited for: ACTIVATION BY ST14.
[11]	"Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa." Camerer E., Huang W., Coughlin S.R. Proc. Natl. Acad. Sci. U.S.A. 97:5255-5260(2000) [PubMed: 10805786] [Abstract] Cited for: ACTIVATION BY COAGULATION FACTORS VII AND XA.
[12]	"Arginine-specific protease from Porphyromonas gingivalis activates protease-activated receptors on human oral epithelial cells and induces interleukin-6 secretion." Lourbakos A., Potempa J., Travis J., D'Andrea M.R., Andrade-Gordon P., Santulli R., Mackie E.J., Pike R.N. Infect. Immun. 69:5121-5130(2001) [PubMed: 11447194] [Abstract] Cited for: FUNCTION, ACTIVATION BY GINGIPAINS.
[13]	"Proteinase-activated receptor-2-mediated activation of stress-activated protein kinases and inhibitory kappa B kinases in NCTC 2544 keratinocytes." Kanke T., Macfarlane S.R., Seatter M.J., Davenport E., Paul A., McKenzie R.C., Plevin R. J. Biol. Chem. 276:31657-31666(2001) [PubMed: 11413129] [Abstract] Cited for: FUNCTION IN JNK AND NF-KAPPA-B PATHWAYS.
[14]	"Interaction of mite allergens Der p3 and Der p9 with protease-activated receptor-2 expressed by lung epithelial cells." Sun G., Stacey M.A., Schmidt M., Mori L., Mattoli S. J. Immunol. 167:1014-1021(2001) [PubMed: 11441110] [Abstract] Cited for: FUNCTION, ACTIVATION BY DUST MITE ALLERGENS.
[15]	"Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2." Miike S., McWilliam A.S., Kita H. J. Immunol. 167:6615-6622(2001) [PubMed: 11714832] [Abstract] Cited for: FUNCTION IN INFLAMMATORY RESPONSE.
[16]	"Glycosylation of human proteinase-activated receptor-2 (hPAR2): role in cell surface expression and signalling." Compton S.J., Sandhu S., Wijesuriya S.J., Hollenberg M.D. Biochem. J. 368:495-505(2002) [PubMed: 12171601] [Abstract] Cited for: GLYCOSYLATION AT ASN-30 AND ASN-222, MUTAGENESIS OF ASN-30 AND ASN-222.
[17]	"Effect of protease-activated receptor-2 deficiency on allergic dermatitis in the mouse ear." Kawagoe J., Takizawa T., Matsumoto J., Tamiya M., Meek S.E., Smith A.J., Hunter G.D., Plevin R., Saito N., Kanke T., Fujii M., Wada Y. Jpn. J. Pharmacol. 88:77-84(2002) [PubMed: 11859856] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN ALLERGIC DERMATITIS.
[18]	"Proteinase-activated receptor-2 and human lung epithelial cells: disarming by neutrophil serine proteinases." Dulon S., Cande C., Bunnett N.W., Hollenberg M.D., Chignard M., Pidard D. Am. J. Respir. Cell Mol. Biol. 28:339-346(2003) [PubMed: 12594060] [Abstract] Cited for: DEACTIVATION BY NEUTROPHIL ELASTASE AND CATHEPSIN G.
[19]	"Proinflammatory role of proteinase-activated receptor-2 in humans and mice during cutaneous inflammation in vivo." Seeliger S., Derian C.K., Vergnolle N., Bunnett N.W., Nawroth R., Schmelz M., Von Der Weid P.Y., Buddenkotte J., Sunderkotter C., Metze D., Andrade-Gordon P., Harms E., Vestweber D., Luger T.A., Steinhoff M. FASEB J. 17:1871-1885(2003) [PubMed: 14519665] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN SKIN DISEASES.
[20]	"Expression of and functional responses to protease-activated receptors on human eosinophils." Bolton S.J., McNulty C.A., Thomas R.J., Hewitt C.R., Wardlaw A.J. J. Leukoc. Biol. 74:60-68(2003) [PubMed: 12832443] [Abstract] Cited for: FUNCTION.
[21]	"The role of the C-terminal tail in protease-activated receptor-2-mediated Ca2+ signalling, proline-rich tyrosine kinase-2 activation, and mitogen-activated protein kinase activity." Seatter M.J., Drummond R., Kanke T., Macfarlane S.R., Hollenberg M.D., Plevin R. Cell. Signal. 16:21-29(2004) [PubMed: 14607272] [Abstract] Cited for: MUTAGENESIS OF 355-ALA--SER-363.
[22]	"Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices." Shpacovitch V.M., Varga G., Strey A., Gunzer M., Mooren F., Buddenkotte J., Vergnolle N., Sommerhoff C.P., Grabbe S., Gerke V., Homey B., Hollenberg M., Luger T.A., Steinhoff M. J. Leukoc. Biol. 76:388-398(2004) [PubMed: 15155775] [Abstract] Cited for: FUNCTION.
[23]	"c-Cbl mediates ubiquitination, degradation, and down-regulation of human protease-activated receptor 2." Jacob C., Cottrell G.S., Gehringer D., Schmidlin F., Grady E.F., Bunnett N.W. J. Biol. Chem. 280:16076-16087(2005) [PubMed: 15708858] [Abstract] Cited for: UBIQUITINATION BY CBL.
[24]	"Protease-activated receptors-1 and -2 can mediate endothelial barrier protection: role in factor Xa signaling." Feistritzer C., Lenta R., Riewald M. J. Thromb. Haemost. 3:2798-2805(2005) [PubMed: 16359518] [Abstract] Cited for: FUNCTION IN ENDOTHELIAL BARRIER PROTECTION.
[25]	"A major role for proteolytic activity and proteinase-activated receptor-2 in the pathogenesis of infectious colitis." Hansen K.K., Sherman P.M., Cellars L., Andrade-Gordon P., Pan Z., Baruch A., Wallace J.L., Hollenberg M.D., Vergnolle N. Proc. Natl. Acad. Sci. U.S.A. 102:8363-8368(2005) [PubMed: 15919826] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN COLITIS.
[26]	"Abrogation of bronchial eosinophilic inflammation and attenuated eotaxin content in protease-activated receptor 2-deficient mice." Takizawa T., Tamiya M., Hara T., Matsumoto J., Saito N., Kanke T., Kawagoe J., Hattori Y. J. Pharmacol. Sci. 98:99-102(2005) [PubMed: 15879675] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN BRONCHIAL EOSINOPHILIC INFLAMMATION.
[27]	"PAR2 activation interrupts E-cadherin adhesion and compromises the airway epithelial barrier: protective effect of beta-agonists." Winter M.C., Shasby S.S., Ries D.R., Shasby D.M. Am. J. Physiol. 291:L628-L635(2006) [PubMed: 16714334] [Abstract] Cited for: FUNCTION IN EPITHELIAL BARRIER DISRUPTION.
[28]	"Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway." Csernok E., Ai M., Gross W.L., Wicklein D., Petersen A., Lindner B., Lamprecht P., Holle J.U., Hellmich B. Blood 107:4440-4448(2006) [PubMed: 16478888] [Abstract] Cited for: FUNCTION, ACTIVATION BY PRTN3.
[29]	"Jab1, a novel protease-activated receptor-2 (PAR-2)-interacting protein, is involved in PAR-2-induced activation of activator protein-1." Luo W., Wang Y., Hanck T., Stricker R., Reiser G. J. Biol. Chem. 281:7927-7936(2006) [PubMed: 16410250] [Abstract] Cited for: FUNCTION, INTERACTION WITH COPS5.
[30]	"Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis." Noorbakhsh F., Tsutsui S., Vergnolle N., Boven L.A., Shariat N., Vodjgani M., Warren K.G., Andrade-Gordon P., Hollenberg M.D., Power C. J. Exp. Med. 203:425-435(2006) [PubMed: 16476770] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN ENCEPHALOMYELITIS AND MULTIPLE SCLEROSIS.
[31]	"Beta-arrestin-dependent regulation of the cofilin pathway downstream of protease-activated receptor-2." Zoudilova M., Kumar P., Ge L., Wang P., Bokoch G.M., DeFea K.A. J. Biol. Chem. 282:20634-20646(2007) [PubMed: 17500066] [Abstract] Cited for: FUNCTION IN ACTIN FILAMENT SEVERING.
[32]	"p24A, a type I transmembrane protein, controls ARF1-dependent resensitization of protease-activated receptor-2 by influence on receptor trafficking." Luo W., Wang Y., Reiser G. J. Biol. Chem. 282:30246-30255(2007) [PubMed: 17693410] [Abstract] Cited for: INTERACTION WITH TMED2.
[33]	"Mold allergen, pen C 13, induces IL-8 expression in human airway epithelial cells by activating protease-activated receptor 1 and 2." Chiu L.L., Perng D.W., Yu C.H., Su S.N., Chow L.P. J. Immunol. 178:5237-5244(2007) [PubMed: 17404307] [Abstract] Cited for: FUNCTION, ACTIVATION BY MOLD ALLERGENS.
[34]	"Chitinase activates protease-activated receptor-2 in human airway epithelial cells." Hong J.H., Hong J.Y., Park B., Lee S.I., Seo J.T., Kim K.E., Sohn M.H., Shin D.M. Am. J. Respir. Cell Mol. Biol. 39:530-535(2008) [PubMed: 18474671] [Abstract] Cited for: FUNCTION, ACTIVATION BY BACTERIAL CHITINASE.
[35]	"G-protein-dependent and -independent pathways regulate proteinase-activated receptor-2 mediated p65 NFkappaB serine 536 phosphorylation in human keratinocytes." Goon Goh F., Sloss C.M., Cunningham M.R., Nilsson M., Cadalbert L., Plevin R. Cell. Signal. 20:1267-1274(2008) [PubMed: 18424071] [Abstract] Cited for: FUNCTION.
[36]	"Analysis of proteinase-activated receptor 2 and TLR4 signal transduction: a novel paradigm for receptor cooperativity." Rallabhandi P., Nhu Q.M., Toshchakov V.Y., Piao W., Medvedev A.E., Hollenberg M.D., Fasano A., Vogel S.N. J. Biol. Chem. 283:24314-24325(2008) [PubMed: 18622013] [Abstract] Cited for: FUNCTION, INTERACTION WITH TLR4.
[37]	"Agonists of proteinase-activated receptor-2 enhance IFN-gamma-inducible effects on human monocytes: role in influenza A infection." Feld M., Shpacovitch V.M., Ehrhardt C., Kerkhoff C., Hollenberg M.D., Vergnolle N., Ludwig S., Steinhoff M. J. Immunol. 180:6903-6910(2008) [PubMed: 18453611] [Abstract] Cited for: FUNCTION IN ANTIVIRAL RESPONSE.
[38]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-373, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[39]	"Endosomal deubiquitinating enzymes control ubiquitination and down-regulation of protease-activated receptor 2." Hasdemir B., Murphy J.E., Cottrell G.S., Bunnett N.W. J. Biol. Chem. 284:28453-28466(2009) [PubMed: 19684015] [Abstract] Cited for: DEUBIQUITINATION.
[40]	"Phosphorylation of protease-activated receptor-2 differentially regulates desensitization and internalization." Ricks T.K., Trejo J. J. Biol. Chem. 284:34444-34457(2009) [PubMed: 19815543] [Abstract] Cited for: PHOSPHORYLATION.
[41]	"Protective role for protease-activated receptor-2 against influenza virus pathogenesis via an IFN-gamma-dependent pathway." Khoufache K., LeBouder F., Morello E., Laurent F., Riffault S., Andrade-Gordon P., Boullier S., Rousset P., Vergnolle N., Riteau B. J. Immunol. 182:7795-7802(2009) [PubMed: 19494303] [Abstract] Cited for: FUNCTION IN ANTIVIRAL RESPONSE.
[42]	"Recognition of fungal protease activities induces cellular activation and eosinophil-derived neurotoxin release in human eosinophils." Matsuwaki Y., Wada K., White T.A., Benson L.M., Charlesworth M.C., Checkel J.L., Inoue Y., Hotta K., Ponikau J.U., Lawrence C.B., Kita H. J. Immunol. 183:6708-6716(2009) [PubMed: 19864598] [Abstract] Cited for: FUNCTION, ACTIVATION BY TRYPSIN AND FUNGAL ASPARTATE PROTEASE.
[43]	"Protease-activated receptor 2: a novel pathogenic pathway in a murine model of osteoarthritis." Ferrell W.R., Kelso E.B., Lockhart J.C., Plevin R., McInnes I.B. Ann. Rheum. Dis. 69:2051-2054(2010) [PubMed: 20584806] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN ARTHRITIS.
[44]	"Proteinase-activated receptor-2 mediated inhibition of TNFalpha-stimulated JNK activation - a novel paradigm for G(q/11) linked GPCRs." McIntosh K., Cunningham M.R., Cadalbert L., Lockhart J., Boyd G., Ferrell W.R., Plevin R. Cell. Signal. 22:265-273(2010) [PubMed: 19781631] [Abstract] Cited for: FUNCTION IN JNK PATHWAY.
[45]	"Factor X/Xa elicits protective signaling responses in endothelial cells directly via PAR-2 and indirectly via endothelial protein C receptor-dependent recruitment of PAR-1." Bae J.S., Yang L., Rezaie A.R. J. Biol. Chem. 285:34803-34812(2010) [PubMed: 20826780] [Abstract] Cited for: FUNCTION IN ENDOTHELIAL BARRIER PROTECTION.
[46]	"Protease-activated receptor-2 (PAR(2)) in human periodontitis." Holzhausen M., Cortelli J.R., da Silva V.A., Franco G.C., Cortelli S.C., Vergnolle N. J. Dent. Res. 89:948-953(2010) [PubMed: 20530726] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN PERIODONTITIS.
[47]	"Novel signaling interactions between proteinase-activated receptor 2 and Toll-like receptors in vitro and in vivo." Nhu Q.M., Shirey K., Teijaro J.R., Farber D.L., Netzel-Arnett S., Antalis T.M., Fasano A., Vogel S.N. Mucosal Immunol. 3:29-39(2010) [PubMed: 19865078] [Abstract] Cited for: FUNCTION.
[48]	"Role of proteinase-activated receptor-2 in anti-bacterial and immunomodulatory effects of interferon-gamma on human neutrophils and monocytes." Shpacovitch V.M., Feld M., Holzinger D., Kido M., Hollenberg M.D., Levi-Schaffer F., Vergnolle N., Ludwig S., Roth J., Luger T., Steinhoff M. Immunology 133:329-339(2011) [PubMed: 21501162] [Abstract] Cited for: FUNCTION IN ANTIMICROBIAL RESPONSE.
[49]	"Palmitoylation of human proteinase-activated receptor-2 differentially regulates receptor triggered ERK1/2 activation, calcium signalling, and endocytosis." Botham A., Guo X., Xiao Y.P., Morice A.H., Compton S.J., Sadofsky L.R. Biochem. J. 438:359-367(2011) [PubMed: 21627585] [Abstract] Cited for: PALMITOYLATION AT CYS-361.
+	Additional computationally mapped references.

Web resources

Wikipedia

Protease-activated receptor entry

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z49993, Z49994 Genomic DNA. Translation: CAA90290.1. U34038 mRNA. Translation: AAB47871.1. AF400075 Genomic DNA. Translation: AAK77914.1. BC012453 mRNA. Translation: AAH12453.1. BC018130 mRNA. Translation: AAH18130.1. U36753 Genomic DNA. Translation: AAA90957.1.
IPI	IPI00296446.
PIR	S66518.
RefSeq	NP_005233.3. NM_005242.4.
UniGene	Hs.154299.
3D structure databases
ProteinModelPortal	P55085.
SMR	P55085. Positions 160-190, 326-361.
ModBase	Search...
Protein-protein interaction databases
IntAct	P55085. 5 interactions.
STRING	P55085.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P55085.
Polymorphism databases
DMDM	1709580.
Proteomic databases
PRIDE	P55085.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296677; ENSP00000296677; ENSG00000164251.
GeneID	2150.
KEGG	hsa:2150.
UCSC	uc003keo.1. human.
Organism-specific databases
CTD	2150.
GeneCards	GC05P076150.
H-InvDB	HIX0004961.
HGNC	HGNC:3538. F2RL1.
HPA	CAB012989.
MIM	600933. gene.
neXtProt	NX_P55085.
PharmGKB	PA27947.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15817.
HOGENOM	HBG714985.
HOVERGEN	HBG105658.
InParanoid	P55085.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P55085.
Bgee	P55085.
CleanEx	HS_F2RL1.
Genevestigator	P55085.
GermOnline	ENSG00000164251. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. IPR002281. Pro_rcpt_2. IPR003912. Protea_act_rcpt. [Graphical view]
KO	K04234.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01428. PROTEASEAR. PR01152. PROTEASEAR2.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. False negative. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	8689.
PMAP-CutDB	P55085.
SOURCE	Search...

Entry information

Entry name

PAR2_HUMAN

Accession

Primary (citable) accession number: P55085
Secondary accession number(s): Q13317, Q13346

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.