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B7UM99

- TIR_ECO27

UniProt

B7UM99 - TIR_ECO27

Protein

Translocated intimin receptor Tir

Gene

tir

Organism
Escherichia coli O127:H6 (strain E2348/69 / EPEC)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 40 (01 Oct 2014)
      Sequence version 1 (10 Feb 2009)
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    Functioni

    Multifunctional protein that is required for efficient pedestal formation in host epithelial cells during infection. The extracellular region acts as a receptor for bacterial intimin, allowing the bacterium to attach tightly to the host-cell surface. Simultaneously, the intracellular region initiates a signaling cascade in the host cell, which leads to actin polymerization and formation of actin pedestals at the sites of bacterial adhesion. In strain E2348/69, acts mainly via the host adaptor proteins NCK1 and NCK2. Once clustered and phosphorylated at Tyr-474, Tir binds to NCK proteins, which in turn bind and activate host WASL/N-WASP, leading to actin polymerization. Can also trigger an inefficient, NCK-independent pedestal formation. This pathway involves phosphorylation of Tyr-454 and probably a putative host adaptor. Acts also via direct binding to the host cytoskeletal protein alpha-actinin in a NCK- and phosphotyrosine-independent manner. This interaction may stabilize the pedestal, but is not essential for its formation.6 Publications

    GO - Molecular functioni

    1. protein binding Source: IntAct

    GO - Biological processi

    1. pathogenesis Source: UniProtKB-KW

    Keywords - Molecular functioni

    Receptor

    Keywords - Biological processi

    Virulence

    Enzyme and pathway databases

    BioCyciECOL574521:GJAO-4084-MONOMER.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Translocated intimin receptor Tir
    Alternative name(s):
    Secreted effector protein Tir
    Gene namesi
    Name:tir
    Synonyms:espE
    Ordered Locus Names:E2348C_3941
    OrganismiEscherichia coli O127:H6 (strain E2348/69 / EPEC)
    Taxonomic identifieri574521 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    ProteomesiUP000008205: Chromosome

    Subcellular locationi

    Secreted. Host cell membrane; Multi-pass membrane protein
    Note: Secreted via the type III secretion system (TTSS). Released into the host cytoplasm via TTSS and then independently inserts into the plasma membrane from a cytoplasmic location. In host cells, localizes to the tip of the actin pedestal.

    GO - Cellular componenti

    1. host cell plasma membrane Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Host cell membrane, Host membrane, Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi452 – 4521N → A: Lack of pedestal formation; when associated with F-474. 1 Publication
    Mutagenesisi453 – 4531P → A: Lack of pedestal formation; when associated with F-474. 1 Publication
    Mutagenesisi454 – 4541Y → A: Lack of pedestal formation; when associated with F-474. 2 Publications
    Mutagenesisi454 – 4541Y → F: Does not inhibit translocation into the host cell. Almost no change in actin polymerization. Lack of pedestal formation; when associated with F-474. 2 Publications
    Mutagenesisi474 – 4741Y → D or E: Loss of phosphorylation and strong decrease in actin polymerization. 4 Publications
    Mutagenesisi474 – 4741Y → F: Loss of phosphorylation and strong decrease in actin polymerization. Lack of pedestal formation; when associated with F-454. 4 Publications
    Mutagenesisi474 – 4741Y → S: Does not inhibit translocation into the host cell. Loss of phosphorylation and strong decrease in actin polymerization. 4 Publications
    Mutagenesisi483 – 4831Y → S: Does not inhibit translocation into the host cell. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 550550Translocated intimin receptor TirPRO_0000414050Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei454 – 4541Phosphotyrosine1 Publication
    Modified residuei474 – 4741Phosphotyrosine2 Publications

    Post-translational modificationi

    Phosphorylated on Tyr-474 by host kinases. Tyr-454 can also be phosphorylated, although at lower efficiency. Phosphorylation is stimulated by clustering of Tir by intimin.6 Publications

    Keywords - PTMi

    Phosphoprotein

    Interactioni

    Subunit structurei

    Interacts with intimin. Interacts with host proteins NCK1, NCK2, alpha-actinin and BAIAP2.10 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    cesTP212446EBI-2504426,EBI-2504434
    CTTNQ142473EBI-2504426,EBI-351886From a different organism.
    PTPN6P293504EBI-2504426,EBI-78260From a different organism.
    Ptpn6P293512EBI-2504426,EBI-2620699From a different organism.

    Protein-protein interaction databases

    DIPiDIP-27648N.
    DIP-55921N.
    IntActiB7UM99. 4 interactions.
    MINTiMINT-7225953.
    STRINGi574521.E2348C_3941.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2CI9X-ray1.50L/M470-481[»]
    2CIAX-ray1.45L472-481[»]
    ProteinModelPortaliB7UM99.
    SMRiB7UM99. Positions 272-336.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiB7UM99.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 233233CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini255 – 362108ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini384 – 550167CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei234 – 25421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei363 – 38321HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi452 – 4543Essential for NCK-independent actin pedestal formation

    Domaini

    The intracellular N-terminal region interacts with host alpha-actinin and is not required for pedestal formation. The central extracellular region (amino acids 277-332) is involved in bacterial intimin binding. The intracellular C-terminal region binds to host NCK.3 Publications

    Sequence similaritiesi

    Belongs to the Tir receptor family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    HOGENOMiHOG000059321.
    KOiK12784.
    OMAiQGIQSTY.
    OrthoDBiEOG63FVXM.

    Family and domain databases

    Gene3Di4.10.820.10. 1 hit.
    InterProiIPR022638. Transloc_intimin_rcpt.
    IPR022639. Transloc_intimin_rcpt_C.
    IPR003536. Transloc_intimin_rcpt_cen_dom.
    IPR022633. Transloc_intimin_rcpt_N.
    [Graphical view]
    PfamiPF07489. Tir_receptor_C. 1 hit.
    PF03549. Tir_receptor_M. 1 hit.
    PF07490. Tir_receptor_N. 1 hit.
    [Graphical view]
    PRINTSiPR01370. TRNSINTIMINR.

    Sequencei

    Sequence statusi: Complete.

    B7UM99-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPIGNLGNNV NGNHLIPPAP PLPSQTDGAA RGGTGHLISS TGALGSRSLF    50
    SPLRNSMADS VDSRDIPGLP TNPSRLAAAT SETCLLGGFE VLHDKGPLDI 100
    LNTQIGPSAF RVEVQADGTH AAIGEKNGLE VSVTLSPQEW SSLQSIDTEG 150
    KNRFVFTGGR GGSGHPMVTV ASDIAEARTK ILAKLDPDNH GGRQPKDVDT 200
    RSVGVGSASG IDDGVVSETH TSTTNSSVRS DPKFWVSVGA IAAGLAGLAA 250
    TGIAQALALT PEPDDPTTTD PDQAANAAES ATKDQLTQEA FKNPENQKVN 300
    IDANGNAIPS GELKDDIVEQ IAQQAKEAGE VARQQAVESN AQAQQRYEDQ 350
    HARRQEELQL SSGIGYGLSS ALIVAGGIGA GVTTALHRRN QPAEQTTTTT 400
    THTVVQQQTG GNTPAQGGTD ATRAEDASLN RRDSQGSVAS THWSDSSSEV 450
    VNPYAEVGGA RNSLSAHQPE EHIYDEVAAD PGYSVIQNFS GSGPVTGRLI 500
    GTPGQGIQST YALLANSGGL RLGMGGLTSG GESAVSSVNA APTPGPVRFV 550
    Length:550
    Mass (Da):56,510
    Last modified:February 10, 2009 - v1
    Checksum:i19DD08A9BE9251CB
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti412 – 43019NTPAQ…DASLN → IPQHKVALMPQERRRFSD in AAB88410. (PubMed:9390560)CuratedAdd
    BLAST
    Sequence conflicti533 – 5331S → T in AAB88410. (PubMed:9390560)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF013122 Genomic DNA. Translation: AAB88410.1.
    AF022236 Genomic DNA. Translation: AAC38390.1.
    FM180568 Genomic DNA. Translation: CAS11489.1.
    RefSeqiWP_001339882.1. NC_011601.1.
    YP_002331403.1. NC_011601.1.

    Genome annotation databases

    EnsemblBacteriaiCAS11489; CAS11489; E2348C_3941.
    GeneIDi7064348.
    KEGGiecg:E2348C_3941.
    PATRICi18347096. VBIEscCol90278_4031.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF013122 Genomic DNA. Translation: AAB88410.1 .
    AF022236 Genomic DNA. Translation: AAC38390.1 .
    FM180568 Genomic DNA. Translation: CAS11489.1 .
    RefSeqi WP_001339882.1. NC_011601.1.
    YP_002331403.1. NC_011601.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2CI9 X-ray 1.50 L/M 470-481 [» ]
    2CIA X-ray 1.45 L 472-481 [» ]
    ProteinModelPortali B7UM99.
    SMRi B7UM99. Positions 272-336.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-27648N.
    DIP-55921N.
    IntActi B7UM99. 4 interactions.
    MINTi MINT-7225953.
    STRINGi 574521.E2348C_3941.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblBacteriai CAS11489 ; CAS11489 ; E2348C_3941 .
    GeneIDi 7064348.
    KEGGi ecg:E2348C_3941.
    PATRICi 18347096. VBIEscCol90278_4031.

    Phylogenomic databases

    HOGENOMi HOG000059321.
    KOi K12784.
    OMAi QGIQSTY.
    OrthoDBi EOG63FVXM.

    Enzyme and pathway databases

    BioCyci ECOL574521:GJAO-4084-MONOMER.

    Miscellaneous databases

    EvolutionaryTracei B7UM99.

    Family and domain databases

    Gene3Di 4.10.820.10. 1 hit.
    InterProi IPR022638. Transloc_intimin_rcpt.
    IPR022639. Transloc_intimin_rcpt_C.
    IPR003536. Transloc_intimin_rcpt_cen_dom.
    IPR022633. Transloc_intimin_rcpt_N.
    [Graphical view ]
    Pfami PF07489. Tir_receptor_C. 1 hit.
    PF03549. Tir_receptor_M. 1 hit.
    PF07490. Tir_receptor_N. 1 hit.
    [Graphical view ]
    PRINTSi PR01370. TRNSINTIMINR.
    ProtoNeti Search...

    Publicationsi

    1. "Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells."
      Kenny B., DeVinney R., Stein M., Reinscheid D.J., Frey E.A., Finlay B.B.
      Cell 91:511-520(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-31, FUNCTION, INTERACTION WITH INTIMIN, SUBCELLULAR LOCATION, SECRETION VIA TYPE III SECRETION SYSTEM, PHOSPHORYLATION, GENE NAME.
      Strain: E2348/69 / EPEC.
    2. "The complete sequence of the locus of enterocyte effacement (LEE) from enteropathogenic Escherichia coli E2348/69."
      Elliott S.J., Wainwright L.A., McDaniel T.K., Jarvis K.G., Deng Y.K., Lai L.C., McNamara B.P., Donnenberg M.S., Kaper J.B.
      Mol. Microbiol. 28:1-4(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: E2348/69 / EPEC.
    3. "Complete genome sequence and comparative genome analysis of enteropathogenic Escherichia coli O127:H6 strain E2348/69."
      Iguchi A., Thomson N.R., Ogura Y., Saunders D., Ooka T., Henderson I.R., Harris D., Asadulghani M., Kurokawa K., Dean P., Kenny B., Quail M.A., Thurston S., Dougan G., Hayashi T., Parkhill J., Frankel G.
      J. Bacteriol. 191:347-354(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: E2348/69 / EPEC.
    4. "EspE, a novel secreted protein of attaching and effacing bacteria, is directly translocated into infected host cells, where it appears as a tyrosine-phosphorylated 90 kDa protein."
      Deibel C., Kramer S., Chakraborty T., Ebel F.
      Mol. Microbiol. 28:463-474(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
      Strain: E2348/69 / EPEC.
    5. "Enterohemorrhagic Escherichia coli O157:H7 produces Tir, which is translocated to the host cell membrane but is not tyrosine phosphorylated."
      DeVinney R., Stein M., Reinscheid D., Abe A., Ruschkowski S., Finlay B.B.
      Infect. Immun. 67:2389-2398(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INTIMIN.
      Strain: E2348/69 / EPEC.
    6. "Phosphorylation of tyrosine 474 of the enteropathogenic Escherichia coli (EPEC) Tir receptor molecule is essential for actin nucleating activity and is preceded by additional host modifications."
      Kenny B.
      Mol. Microbiol. 31:1229-1241(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, INTERACTION WITH INTIMIN, PHOSPHORYLATION, MUTAGENESIS OF TYR-474 AND TYR-483.
      Strain: E2348/69 / EPEC.
    7. "Enteropathogenic E. coli translocated intimin receptor, Tir, interacts directly with alpha-actinin."
      Goosney D.L., DeVinney R., Pfuetzner R.A., Frey E.A., Strynadka N.C., Finlay B.B.
      Curr. Biol. 10:735-738(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HOST ALPHA-ACTININ, DOMAIN.
      Strain: EPEC.
    8. "Enteropathogenic E. coli Tir binds Nck to initiate actin pedestal formation in host cells."
      Gruenheid S., DeVinney R., Bladt F., Goosney D., Gelkop S., Gish G.D., Pawson T., Finlay B.B.
      Nat. Cell Biol. 3:856-859(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HOST NCK.
      Strain: E2348/69 / EPEC.
    9. "A tyrosine-phosphorylated 12-amino-acid sequence of enteropathogenic Escherichia coli Tir binds the host adaptor protein Nck and is required for Nck localization to actin pedestals."
      Campellone K.G., Giese A., Tipper D.J., Leong J.M.
      Mol. Microbiol. 43:1227-1241(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HOST NCK, PHOSPHORYLATION, MUTAGENESIS OF TYR-474.
      Strain: E2348/69 / EPEC.
    10. "Enterohaemorrhagic and enteropathogenic Escherichia coli use different mechanisms for actin pedestal formation that converge on N-WASP."
      Lommel S., Benesch S., Rohde M., Wehland J., Rottner K.
      Cell. Microbiol. 6:243-254(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
      Strain: E2348/69 / EPEC.
    11. "Clustering of Nck by a 12-residue Tir phosphopeptide is sufficient to trigger localized actin assembly."
      Campellone K.G., Rankin S., Pawson T., Kirschner M.W., Tipper D.J., Leong J.M.
      J. Cell Biol. 164:407-416(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH INTIMIN AND HOST NCK, PHOSPHORYLATION, DOMAIN.
      Strain: E2348/69 / EPEC.
    12. "Nck-independent actin assembly is mediated by two phosphorylated tyrosines within enteropathogenic Escherichia coli Tir."
      Campellone K.G., Leong J.M.
      Mol. Microbiol. 56:416-432(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH HOST NCK, PHOSPHORYLATION AT TYR-454 AND TYR-474, MUTAGENESIS OF TYR-454 AND TYR-474.
      Strain: E2348/69 / EPEC.
    13. "Insertion of the enteropathogenic Escherichia coli Tir virulence protein into membranes in vitro."
      Race P.R., Lakey J.H., Banfield M.J.
      J. Biol. Chem. 281:7842-7849(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
      Strain: EPEC.
    14. "Enterohaemorrhagic and enteropathogenic Escherichia coli Tir proteins trigger a common Nck-independent actin assembly pathway."
      Brady M.J., Campellone K.G., Ghildiyal M., Leong J.M.
      Cell. Microbiol. 9:2242-2253(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASN-452; PRO-453; TYR-454 AND TYR-474.
      Strain: E2348/69 / EPEC.
    15. "IRSp53 links the enterohemorrhagic E. coli effectors Tir and EspFU for actin pedestal formation."
      Weiss S.M., Ladwein M., Schmidt D., Ehinger J., Lommel S., Stading K., Beutling U., Disanza A., Frank R., Jansch L., Scita G., Gunzer F., Rottner K., Stradal T.E.
      Cell Host Microbe 5:244-258(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HOST BAIAP2.
      Strain: E2348/69 / EPEC.
    16. "Cytoskeleton-modulating effectors of enteropathogenic and enterohaemorrhagic Escherichia coli: Tir, EspFU and actin pedestal assembly."
      Campellone K.G.
      FEBS J. 277:2390-2402(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    17. "The phosphotyrosine peptide binding specificity of Nck1 and Nck2 Src homology 2 domains."
      Frese S., Schubert W.D., Findeis A.C., Marquardt T., Roske Y.S., Stradal T.E., Heinz D.W.
      J. Biol. Chem. 281:18236-18245(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 472-481 IN COMPLEX WITH NCK1 AND NCK2, PHOSPHORYLATION AT TYR-474.

    Entry informationi

    Entry nameiTIR_ECO27
    AccessioniPrimary (citable) accession number: B7UM99
    Secondary accession number(s): O50190, O52147
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 14, 2011
    Last sequence update: February 10, 2009
    Last modified: October 1, 2014
    This is version 40 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3