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P55085

- PAR2_HUMAN

UniProt

P55085 - PAR2_HUMAN

Protein

Proteinase-activated receptor 2

Gene

F2RL1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    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 PubMed:21627585 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.24 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei36 – 372Cleavage; by trypsin

    GO - Molecular functioni

    1. G-protein alpha-subunit binding Source: UniProtKB
    2. G-protein beta-subunit binding Source: UniProtKB
    3. G-protein coupled receptor activity Source: UniProtKB
    4. protein binding Source: IntAct
    5. receptor activity Source: ProtInc
    6. receptor binding Source: ProtInc
    7. thrombin receptor activity Source: InterPro

    GO - Biological processi

    1. blood coagulation Source: InterPro
    2. chemokine (C-C motif) ligand 2 secretion Source: UniProtKB
    3. chemokine secretion Source: UniProtKB
    4. defense response to virus Source: UniProtKB
    5. establishment of endothelial barrier Source: UniProtKB
    6. G-protein coupled receptor signaling pathway Source: ProtInc
    7. inflammatory response Source: UniProtKB-KW
    8. innate immune response Source: UniProtKB-KW
    9. interferon-gamma secretion Source: UniProtKB
    10. interleukin-10 secretion Source: UniProtKB
    11. interleukin-1 beta secretion Source: UniProtKB
    12. leukocyte migration Source: UniProtKB
    13. leukocyte proliferation Source: UniProtKB
    14. mature dendritic cell differentiation Source: UniProtKB
    15. negative regulation of chemokine secretion Source: UniProtKB
    16. negative regulation of JNK cascade Source: UniProtKB
    17. negative regulation of toll-like receptor 3 signaling pathway Source: UniProtKB
    18. negative regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
    19. neutrophil activation Source: UniProtKB
    20. positive regulation of actin filament depolymerization Source: UniProtKB
    21. positive regulation of cell migration Source: UniProtKB
    22. positive regulation of chemotaxis Source: UniProtKB
    23. positive regulation of cytokine secretion involved in immune response Source: UniProtKB
    24. positive regulation of cytosolic calcium ion concentration Source: UniProtKB
    25. positive regulation of eosinophil degranulation Source: UniProtKB
    26. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    27. positive regulation of glomerular filtration Source: UniProtKB
    28. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    29. positive regulation of interleukin-6 secretion Source: UniProtKB
    30. positive regulation of interleukin-8 secretion Source: UniProtKB
    31. positive regulation of JNK cascade Source: UniProtKB
    32. positive regulation of leukocyte chemotaxis Source: BHF-UCL
    33. positive regulation of neutrophil mediated killing of gram-negative bacterium Source: UniProtKB
    34. positive regulation of phagocytosis, engulfment Source: UniProtKB
    35. positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
    36. positive regulation of positive chemotaxis Source: BHF-UCL
    37. positive regulation of pseudopodium assembly Source: UniProtKB
    38. positive regulation of renin secretion into blood stream Source: UniProtKB
    39. positive regulation of Rho protein signal transduction Source: UniProtKB
    40. positive regulation of superoxide anion generation Source: UniProtKB
    41. positive regulation of toll-like receptor 2 signaling pathway Source: UniProtKB
    42. positive regulation of toll-like receptor 3 signaling pathway Source: UniProtKB
    43. positive regulation of toll-like receptor 4 signaling pathway Source: UniProtKB
    44. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    45. positive regulation of vasodilation Source: UniProtKB
    46. regulation of blood coagulation Source: BHF-UCL
    47. regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    48. regulation of JNK cascade Source: UniProtKB
    49. T cell activation involved in immune response Source: UniProtKB

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Keywords - Biological processi

    Immunity, Inflammatory response, Innate immunity

    Enzyme and pathway databases

    ReactomeiREACT_14819. Peptide ligand-binding receptors.
    REACT_18283. G alpha (q) signalling events.

    Names & Taxonomyi

    Protein namesi
    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:
    Gene namesi
    Name:F2RL1
    Synonyms:GPR11, PAR2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:3538. F2RL1.

    Subcellular locationi

    GO - Cellular componenti

    1. Golgi apparatus Source: ProtInc
    2. integral component of plasma membrane Source: BHF-UCL
    3. plasma membrane Source: Reactome
    4. pseudopodium Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi30 – 301N → A: Decreases cell surface expression; when associate with A-222. 2 Publications
    Mutagenesisi30 – 301N → A: Increase of sensitivity towards tryptase. 2 Publications
    Mutagenesisi222 – 2221N → A: Decreases cell surface expression; when associate with A-30. 2 Publications
    Mutagenesisi222 – 2221N → A: Loss of sensitivity towards all tested proteases. 2 Publications
    Mutagenesisi355 – 3639Missing: Abolishes signaling through accumulation of intracellular calcium and phosphoinositide; no effect in signaling through MAPK. 1 Publication
    Mutagenesisi361 – 3611C → 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. 1 Publication
    Mutagenesisi363 – 3631S → A: Reduces receptor desensitization and internalization, activates ERK1/2; when associated with A-366. 2 Publications
    Mutagenesisi366 – 3661T → A: Reduces receptor desensitization and internalization, activates ERK1/2; when associated with A-363. 2 Publications

    Organism-specific databases

    PharmGKBiPA27947.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2525Sequence AnalysisAdd
    BLAST
    Propeptidei26 – 3611Removed for receptor activationPRO_0000012750Add
    BLAST
    Chaini37 – 397361Proteinase-activated receptor 2PRO_0000412954Add
    BLAST
    Chaini38 – 397360Proteinase-activated receptor 2, alternate cleaved 1PRO_0000412956Add
    BLAST
    Chaini39 – 397359Proteinase-activated receptor 2, alternate cleaved 2PRO_0000012751Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi30 – 301N-linked (GlcNAc...)1 Publication
    Disulfide bondi148 ↔ 226PROSITE-ProRule annotation
    Glycosylationi222 – 2221N-linked (GlcNAc...)1 Publication
    Lipidationi361 – 3611S-palmitoyl cysteine1 Publication

    Post-translational modificationi

    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.1 Publication
    N-glycosylated and sialylated.1 Publication
    Multiple phosphorylated on serine and threonine residues in the cytoplasmic region upon receptor activation; required for receptor desensitization and recruitment of beta-arrestin.1 Publication
    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.

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP55085.
    PaxDbiP55085.
    PRIDEiP55085.

    PTM databases

    PhosphoSiteiP55085.

    Miscellaneous databases

    PMAP-CutDBP55085.

    Expressioni

    Tissue specificityi

    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.

    Gene expression databases

    ArrayExpressiP55085.
    BgeeiP55085.
    CleanExiHS_F2RL1.
    GenevestigatoriP55085.

    Organism-specific databases

    HPAiCAB012989.

    Interactioni

    Subunit structurei

    Interacts with TLR4, COPS5 and TMED2. Interacts with GNAQ, GNA11, GNA12, GNA13 and GNA14 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CBLP226813EBI-4303189,EBI-518228
    COPS5Q929058EBI-4303189,EBI-594661
    EPR-1Q148684EBI-4303189,EBI-4309771
    TMED2Q153636EBI-4303189,EBI-998485

    Protein-protein interaction databases

    BioGridi108449. 4 interactions.
    IntActiP55085. 6 interactions.
    MINTiMINT-1326650.
    STRINGi9606.ENSP00000296677.

    Structurei

    3D structure databases

    ProteinModelPortaliP55085.
    SMRiP55085. Positions 38-352.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini37 – 7539ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini102 – 1109CytoplasmicSequence Analysis
    Topological domaini131 – 14919ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini172 – 19019CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini212 – 24130ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini261 – 28525CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini309 – 32315ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini348 – 39750CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei76 – 10126Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei111 – 13020Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei150 – 17122Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei191 – 21121Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei242 – 26019Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei286 – 30823Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei324 – 34724Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi383 – 3908Poly-Ser

    Sequence similaritiesi

    Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG145128.
    HOGENOMiHOG000116291.
    HOVERGENiHBG105658.
    InParanoidiP55085.
    KOiK04234.
    PhylomeDBiP55085.
    TreeFamiTF330775.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    InterProiIPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    IPR002281. Pro_rcpt_2.
    IPR003912. Protea_act_rcpt.
    [Graphical view]
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR00237. GPCRRHODOPSN.
    PR01428. PROTEASEAR.
    PR01152. PROTEASEAR2.
    PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P55085-1 [UniParc]FASTAAdd to Basket

    « Hide

    MRSPSAAWLL GAAILLAASL SCSGTIQGTN RSSKGRSLIG KVDGTSHVTG    50
    KGVTVETVFS VDEFSASVLT GKLTTVFLPI VYTIVFVVGL PSNGMALWVF 100
    LFRTKKKHPA VIYMANLALA DLLSVIWFPL KIAYHIHGNN WIYGEALCNV 150
    LIGFFYGNMY CSILFMTCLS VQRYWVIVNP MGHSRKKANI AIGISLAIWL 200
    LILLVTIPLY VVKQTIFIPA LNITTCHDVL PEQLLVGDMF NYFLSLAIGV 250
    FLFPAFLTAS AYVLMIRMLR SSAMDENSEK KRKRAIKLIV TVLAMYLICF 300
    TPSNLLLVVH YFLIKSQGQS HVYALYIVAL CLSTLNSCID PFVYYFVSHD 350
    FRDHAKNALL CRSVRTVKQM QVSLTSKKHS RKSSSYSSSS TTVKTSY 397
    Length:397
    Mass (Da):44,126
    Last modified:October 1, 1996 - v1
    Checksum:iF1A4E1D5AB9B362B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti138 – 1381G → A in AAB47871. (PubMed:8615752)Curated
    Sequence conflicti291 – 2911T → S in AAH18130. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti21 – 211S → F.1 Publication
    Corresponds to variant rs2243072 [ dbSNP | Ensembl ].
    VAR_012846
    Natural varianti30 – 301N → S.
    Corresponds to variant rs616235 [ dbSNP | Ensembl ].
    VAR_049435
    Natural varianti270 – 2701R → Q.1 Publication
    Corresponds to variant rs2243062 [ dbSNP | Ensembl ].
    VAR_012847
    Natural varianti291 – 2911T → A.1 Publication
    Corresponds to variant rs2243083 [ dbSNP | Ensembl ].
    VAR_012848

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS4033.1.
    PIRiS66518.
    RefSeqiNP_005233.3. NM_005242.4.
    UniGeneiHs.744181.

    Genome annotation databases

    EnsembliENST00000296677; ENSP00000296677; ENSG00000164251.
    GeneIDi2150.
    KEGGihsa:2150.
    UCSCiuc003keo.3. human.

    Polymorphism databases

    DMDMi1709580.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Protease-activated receptor entry

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS4033.1.
    PIRi S66518.
    RefSeqi NP_005233.3. NM_005242.4.
    UniGenei Hs.744181.

    3D structure databases

    ProteinModelPortali P55085.
    SMRi P55085. Positions 38-352.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108449. 4 interactions.
    IntActi P55085. 6 interactions.
    MINTi MINT-1326650.
    STRINGi 9606.ENSP00000296677.

    Chemistry

    BindingDBi P55085.
    ChEMBLi CHEMBL5963.
    GuidetoPHARMACOLOGYi 348.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P55085.

    Polymorphism databases

    DMDMi 1709580.

    Proteomic databases

    MaxQBi P55085.
    PaxDbi P55085.
    PRIDEi P55085.

    Protocols and materials databases

    DNASUi 2150.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000296677 ; ENSP00000296677 ; ENSG00000164251 .
    GeneIDi 2150.
    KEGGi hsa:2150.
    UCSCi uc003keo.3. human.

    Organism-specific databases

    CTDi 2150.
    GeneCardsi GC05P076120.
    HGNCi HGNC:3538. F2RL1.
    HPAi CAB012989.
    MIMi 600933. gene.
    neXtProti NX_P55085.
    PharmGKBi PA27947.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG145128.
    HOGENOMi HOG000116291.
    HOVERGENi HBG105658.
    InParanoidi P55085.
    KOi K04234.
    PhylomeDBi P55085.
    TreeFami TF330775.

    Enzyme and pathway databases

    Reactomei REACT_14819. Peptide ligand-binding receptors.
    REACT_18283. G alpha (q) signalling events.

    Miscellaneous databases

    GeneWikii Protease_activated_receptor_2.
    GenomeRNAii 2150.
    NextBioi 8689.
    PMAP-CutDB P55085.
    PROi P55085.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P55085.
    Bgeei P55085.
    CleanExi HS_F2RL1.
    Genevestigatori P55085.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    IPR002281. Pro_rcpt_2.
    IPR003912. Protea_act_rcpt.
    [Graphical view ]
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00237. GPCRRHODOPSN.
    PR01428. PROTEASEAR.
    PR01152. PROTEASEAR2.
    PROSITEi PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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. Cited for: ACTIVATION BY MAST CELL TRYPTASE.
    10. 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. 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. 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.

    Entry informationi

    Entry nameiPAR2_HUMAN
    AccessioniPrimary (citable) accession number: P55085
    Secondary accession number(s): Q13317, Q13346, Q53XJ8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 140 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    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.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3