Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P55085 (PAR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:F2RL1
Synonyms:GPR11, PAR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length397 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 vasodilation. 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.50 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.3 Ref.10 Ref.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.23 Ref.25 Ref.27 Ref.30 Ref.31 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.42 Ref.43 Ref.45 Ref.46 Ref.48 Ref.49

Subunit structure

Interacts with TLR4, COPS5 and TMED2. Interacts with GNAQ, GNA11, GNA12, GNA13 and GNA14 By similarity. Ref.3 Ref.34 Ref.38

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.19

Multiple phosphorylated on serine and threonine residues in the cytoplasmic region upon receptor activation; required for receptor desensitization and recruitment of beta-arrestin. Ref.41

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 processImmunity
Inflammatory response
Innate immunity
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

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.49. Source: UniProtKB

chemokine secretion

Inferred from direct assay Ref.42Ref.49. Source: UniProtKB

defense response to virus

Inferred from direct assay Ref.39Ref.42. Source: UniProtKB

establishment of endothelial barrier

Inferred from direct assay Ref.46. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

interferon-gamma secretion

Inferred from sequence or structural similarity. Source: UniProtKB

interleukin-1 beta secretion

Inferred from direct assay Ref.25. Source: UniProtKB

interleukin-10 secretion

Inferred from direct assay Ref.39. Source: UniProtKB

leukocyte migration

Inferred from direct assay Ref.25. Source: UniProtKB

leukocyte proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

mature dendritic cell differentiation

Inferred from direct assay Ref.31. Source: UniProtKB

negative regulation of JNK cascade

Inferred from direct assay Ref.45. Source: UniProtKB

negative regulation of chemokine secretion

Inferred from direct assay Ref.48. Source: UniProtKB

negative regulation of toll-like receptor 3 signaling pathway

Inferred from mutant phenotype Ref.48. Source: UniProtKB

negative regulation of tumor necrosis factor-mediated signaling pathway

Inferred from direct assay Ref.45. Source: UniProtKB

neutrophil activation

Inferred from direct assay Ref.25. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay Ref.12. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay Ref.16. Source: UniProtKB

positive regulation of JNK cascade

Inferred from direct assay Ref.16. Source: UniProtKB

positive regulation of Rho protein signal transduction

Inferred from mutant phenotype Ref.46. Source: UniProtKB

positive regulation of actin filament depolymerization

Inferred from direct assay Ref.33. Source: UniProtKB

positive regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytokine secretion involved in immune response

Inferred from direct assay Ref.17. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from direct assay Ref.12. Source: UniProtKB

positive regulation of eosinophil degranulation

Inferred from direct assay Ref.18. Source: UniProtKB

positive regulation of glomerular filtration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-6 secretion

Inferred from direct assay Ref.15Ref.25. Source: UniProtKB

positive regulation of interleukin-8 secretion

Inferred from direct assay Ref.25Ref.35Ref.38Ref.48. Source: UniProtKB

positive regulation of leukocyte chemotaxis

Inferred from direct assay PubMed 17991872. Source: BHF-UCL

positive regulation of neutrophil mediated killing of gram-negative bacterium

Inferred from direct assay Ref.49. Source: UniProtKB

positive regulation of phagocytosis, engulfment

Inferred from direct assay Ref.49. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of positive chemotaxis

Inferred from direct assay PubMed 17991872. Source: BHF-UCL

positive regulation of pseudopodium assembly

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of renin secretion into blood stream

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of superoxide anion generation

Inferred from direct assay Ref.18. Source: UniProtKB

positive regulation of toll-like receptor 2 signaling pathway

Inferred from mutant phenotype Ref.48. Source: UniProtKB

positive regulation of toll-like receptor 3 signaling pathway

Inferred from mutant phenotype Ref.48. Source: UniProtKB

positive regulation of toll-like receptor 4 signaling pathway

Inferred from direct assay Ref.38. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.3. Source: UniProtKB

positive regulation of vasodilation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay Ref.39. Source: UniProtKB

regulation of JNK cascade

Inferred from direct assay Ref.3. Source: UniProtKB

regulation of blood coagulation

Inferred from direct assay PubMed 17848177. Source: BHF-UCL

   Cellular_componentGolgi apparatus

Traceable author statement Ref.2. Source: ProtInc

integral component of plasma membrane

Inferred from direct assay PubMed 17848177. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

pseudopodium

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionG-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

G-protein coupled receptor activity

Inferred from mutant phenotype Ref.38. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.26Ref.3Ref.34Ref.46PubMed 21219331. Source: IntAct

receptor activity

Traceable author statement Ref.2. Source: ProtInc

receptor binding

Traceable author statement Ref.2. Source: ProtInc

thrombin receptor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Propeptide26 – 3611Removed for receptor activation
PRO_0000012750
Chain37 – 397361Proteinase-activated receptor 2
PRO_0000412954
Chain38 – 397360Proteinase-activated receptor 2, alternate cleaved 1
PRO_0000412956
Chain39 – 397359Proteinase-activated receptor 2, alternate cleaved 2
PRO_0000012751

Regions

Topological domain37 – 7539Extracellular Potential
Transmembrane76 – 10126Helical; Name=1; Potential
Topological domain102 – 1109Cytoplasmic Potential
Transmembrane111 – 13020Helical; Name=2; Potential
Topological domain131 – 14919Extracellular Potential
Transmembrane150 – 17122Helical; Name=3; Potential
Topological domain172 – 19019Cytoplasmic Potential
Transmembrane191 – 21121Helical; Name=4; Potential
Topological domain212 – 24130Extracellular Potential
Transmembrane242 – 26019Helical; Name=5; Potential
Topological domain261 – 28525Cytoplasmic Potential
Transmembrane286 – 30823Helical; Name=6; Potential
Topological domain309 – 32315Extracellular Potential
Transmembrane324 – 34724Helical; Name=7; Potential
Topological domain348 – 39750Cytoplasmic Potential
Compositional bias383 – 3908Poly-Ser

Sites

Site36 – 372Cleavage; by trypsin

Amino acid modifications

Lipidation3611S-palmitoyl cysteine Ref.50
Glycosylation301N-linked (GlcNAc...) Ref.19
Glycosylation2221N-linked (GlcNAc...) Ref.19
Disulfide bond148 ↔ 226 By similarity

Natural variations

Natural variant211S → F. Ref.4
Corresponds to variant rs2243072 [ dbSNP | Ensembl ].
VAR_012846
Natural variant301N → S.
Corresponds to variant rs616235 [ dbSNP | Ensembl ].
VAR_049435
Natural variant2701R → Q. Ref.4
Corresponds to variant rs2243062 [ dbSNP | Ensembl ].
VAR_012847
Natural variant2911T → A. Ref.4
Corresponds to variant rs2243083 [ dbSNP | Ensembl ].
VAR_012848

Experimental info

Mutagenesis301N → A: Decreases cell surface expression; when associate with A-222. Ref.19
Mutagenesis301N → A: Increase of sensitivity towards tryptase. Ref.19
Mutagenesis2221N → A: Decreases cell surface expression; when associate with A-30. Ref.19
Mutagenesis2221N → A: Loss of sensitivity towards all tested proteases. Ref.19
Mutagenesis355 – 3639Missing: Abolishes signaling through accumulation of intracellular calcium and phosphoinositide; no effect in signaling through MAPK. Ref.12 Ref.24
Mutagenesis3611C → 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.
Mutagenesis3631S → A: Reduces receptor desensitization and internalization, activates ERK1/2; when associated with A-366. Ref.12
Mutagenesis3661T → A: Reduces receptor desensitization and internalization, activates ERK1/2; when associated with A-363. Ref.12
Sequence conflict1381G → A in AAB47871. Ref.2
Sequence conflict2911T → S in AAH18130. Ref.7

Sequences

Sequence LengthMass (Da)Tools
P55085 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: F1A4E1D5AB9B362B

FASTA39744,126
        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 

« Hide

References

« Hide 'large scale' references
[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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Kidney.
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH COPS5.
[4]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.
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Ovary and Pancreas.
[8]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-397.
[9]"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] [Europe PMC] [Abstract]
Cited for: ACTIVATION BY MAST CELL TRYPTASE.
[10]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN EPITHELIAL BARRIER PROTECTION.
[11]"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] [Europe PMC] [Abstract]
Cited for: TRANSACTIVATION BY F2R.
[12]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF SER-363 AND THR-366.
[13]"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] [Europe PMC] [Abstract]
Cited for: ACTIVATION BY ST14.
[14]"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] [Europe PMC] [Abstract]
Cited for: ACTIVATION BY COAGULATION FACTORS VII AND XA.
[15]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, ACTIVATION BY GINGIPAINS.
[16]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN JNK AND NF-KAPPA-B PATHWAYS.
[17]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, ACTIVATION BY DUST MITE ALLERGENS.
[18]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INFLAMMATORY RESPONSE.
[19]"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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-30 AND ASN-222, MUTAGENESIS OF ASN-30 AND ASN-222.
[20]"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] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN ALLERGIC DERMATITIS.
[21]"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] [Europe PMC] [Abstract]
Cited for: DEACTIVATION BY NEUTROPHIL ELASTASE AND CATHEPSIN G.
[22]"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] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN SKIN DISEASES.
[23]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[24]"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] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 355-ALA--SER-363.
[25]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[26]"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] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY CBL.
[27]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ENDOTHELIAL BARRIER PROTECTION.
[28]"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] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN COLITIS.
[29]"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] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN BRONCHIAL EOSINOPHILIC INFLAMMATION.
[30]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN EPITHELIAL BARRIER DISRUPTION.
[31]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, ACTIVATION BY PRTN3.
[32]"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] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN ENCEPHALOMYELITIS AND MULTIPLE SCLEROSIS.
[33]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIN FILAMENT SEVERING.
[34]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TMED2.
[35]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, ACTIVATION BY MOLD ALLERGENS.
[36]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, ACTIVATION BY BACTERIAL CHITINASE.
[37]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[38]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TLR4.
[39]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ANTIVIRAL RESPONSE.
[40]"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] [Europe PMC] [Abstract]
Cited for: DEUBIQUITINATION.
[41]"Phosphorylation of protease-activated receptor-2 differentially regulates desensitization and internalization."
Ricks T.K., Trejo J.
J. Biol. Chem. 284:34444-34457(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[42]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ANTIVIRAL RESPONSE.
[43]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, ACTIVATION BY TRYPSIN AND FUNGAL ASPARTATE PROTEASE.
[44]"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] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN ARTHRITIS.
[45]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN JNK PATHWAY.
[46]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ENDOTHELIAL BARRIER PROTECTION.
[47]"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] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN PERIODONTITIS.
[48]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[49]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ANTIMICROBIAL RESPONSE.
[50]"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] [Europe PMC] [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.
AY336105 mRNA. Translation: AAP97012.1.
AF400075 Genomic DNA. Translation: AAK77914.1.
BT009856 mRNA. Translation: AAP88858.1.
CH471084 Genomic DNA. Translation: EAW95782.1.
BC012453 mRNA. Translation: AAH12453.1.
BC018130 mRNA. Translation: AAH18130.1.
U36753 Genomic DNA. Translation: AAA90957.1.
CCDSCCDS4033.1.
PIRS66518.
RefSeqNP_005233.3. NM_005242.4.
UniGeneHs.744181.

3D structure databases

ProteinModelPortalP55085.
SMRP55085. Positions 38-352.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108449. 4 interactions.
IntActP55085. 6 interactions.
MINTMINT-1326650.
STRING9606.ENSP00000296677.

Chemistry

BindingDBP55085.
ChEMBLCHEMBL5963.
GuidetoPHARMACOLOGY348.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP55085.

Polymorphism databases

DMDM1709580.

Proteomic databases

MaxQBP55085.
PaxDbP55085.
PRIDEP55085.

Protocols and materials databases

DNASU2150.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296677; ENSP00000296677; ENSG00000164251.
GeneID2150.
KEGGhsa:2150.
UCSCuc003keo.3. human.

Organism-specific databases

CTD2150.
GeneCardsGC05P076120.
HGNCHGNC:3538. F2RL1.
HPACAB012989.
MIM600933. gene.
neXtProtNX_P55085.
PharmGKBPA27947.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG145128.
HOGENOMHOG000116291.
HOVERGENHBG105658.
InParanoidP55085.
KOK04234.
PhylomeDBP55085.
TreeFamTF330775.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP55085.
BgeeP55085.
CleanExHS_F2RL1.
GenevestigatorP55085.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002281. Pro_rcpt_2.
IPR003912. Protea_act_rcpt.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR01428. PROTEASEAR.
PR01152. PROTEASEAR2.
PROSITEPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiProtease_activated_receptor_2.
GenomeRNAi2150.
NextBio8689.
PMAP-CutDBP55085.
PROP55085.
SOURCESearch...

Entry information

Entry namePAR2_HUMAN
AccessionPrimary (citable) accession number: P55085
Secondary accession number(s): Q13317, Q13346, Q53XJ8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries