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B7UM99

- TIR_ECO27

UniProt

B7UM99 - TIR_ECO27

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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

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 - Biological processi

  1. pathogenesis Source: UniProtKB-KW
Complete GO annotation...

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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 233233CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei234 – 25421HelicalSequence AnalysisAdd
BLAST
Topological domaini255 – 362108ExtracellularSequence AnalysisAdd
BLAST
Transmembranei363 – 38321HelicalSequence AnalysisAdd
BLAST
Topological domaini384 – 550167CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

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:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CI9X-ray1.50L/M470-481[»]
2CIAX-ray1.45L472-481[»]
ProteinModelPortaliB7UM99.
SMRiB7UM99. Positions 272-336.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiB7UM99.

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

        10         20         30         40         50
MPIGNLGNNV NGNHLIPPAP PLPSQTDGAA RGGTGHLISS TGALGSRSLF
60 70 80 90 100
SPLRNSMADS VDSRDIPGLP TNPSRLAAAT SETCLLGGFE VLHDKGPLDI
110 120 130 140 150
LNTQIGPSAF RVEVQADGTH AAIGEKNGLE VSVTLSPQEW SSLQSIDTEG
160 170 180 190 200
KNRFVFTGGR GGSGHPMVTV ASDIAEARTK ILAKLDPDNH GGRQPKDVDT
210 220 230 240 250
RSVGVGSASG IDDGVVSETH TSTTNSSVRS DPKFWVSVGA IAAGLAGLAA
260 270 280 290 300
TGIAQALALT PEPDDPTTTD PDQAANAAES ATKDQLTQEA FKNPENQKVN
310 320 330 340 350
IDANGNAIPS GELKDDIVEQ IAQQAKEAGE VARQQAVESN AQAQQRYEDQ
360 370 380 390 400
HARRQEELQL SSGIGYGLSS ALIVAGGIGA GVTTALHRRN QPAEQTTTTT
410 420 430 440 450
THTVVQQQTG GNTPAQGGTD ATRAEDASLN RRDSQGSVAS THWSDSSSEV
460 470 480 490 500
VNPYAEVGGA RNSLSAHQPE EHIYDEVAAD PGYSVIQNFS GSGPVTGRLI
510 520 530 540 550
GTPGQGIQST YALLANSGGL RLGMGGLTSG GESAVSSVNA APTPGPVRFV
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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

« Hide 'large scale' publications
  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 29, 2014
This is version 41 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