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Protein

Translocated intimin receptor Tir

Gene

tir

Organism
Escherichia coli O127:H6 (strain E2348/69 / EPEC)
Status
Reviewed-Annotation score: 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

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Virulence

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 lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000008205 Componenti: 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)DescriptionActionsGraphical viewLength
Topological domaini1 – 233CytoplasmicSequence analysisAdd BLAST233
Transmembranei234 – 254HelicalSequence analysisAdd BLAST21
Topological domaini255 – 362ExtracellularSequence analysisAdd BLAST108
Transmembranei363 – 383HelicalSequence analysisAdd BLAST21
Topological domaini384 – 550CytoplasmicSequence analysisAdd BLAST167

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi452N → A: Lack of pedestal formation; when associated with F-474. 1 Publication1
Mutagenesisi453P → A: Lack of pedestal formation; when associated with F-474. 1 Publication1
Mutagenesisi454Y → A: Lack of pedestal formation; when associated with F-474. 2 Publications1
Mutagenesisi454Y → 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 Publications1
Mutagenesisi474Y → D or E: Loss of phosphorylation and strong decrease in actin polymerization. 4 Publications1
Mutagenesisi474Y → F: Loss of phosphorylation and strong decrease in actin polymerization. Lack of pedestal formation; when associated with F-454. 4 Publications1
Mutagenesisi474Y → S: Does not inhibit translocation into the host cell. Loss of phosphorylation and strong decrease in actin polymerization. 4 Publications1
Mutagenesisi483Y → S: Does not inhibit translocation into the host cell. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004140501 – 550Translocated intimin receptor TirAdd BLAST550

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei454Phosphotyrosine1 Publication1
Modified residuei474Phosphotyrosine2 Publications1

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

PTM databases

iPTMnetiB7UM99.

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. 9 interactors.
MINTiMINT-7225953.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CI9X-ray1.50L/M470-481[»]
2CIAX-ray1.45L472-481[»]
ProteinModelPortaliB7UM99.
SMRiB7UM99.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiB7UM99.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi452 – 454Essential for NCK-independent actin pedestal formation3

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.

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)DescriptionActionsGraphical viewLength
Sequence conflicti412 – 430NTPAQ…DASLN → IPQHKVALMPQERRRFSD in AAB88410 (PubMed:9390560).CuratedAdd BLAST19
Sequence conflicti533S → T in AAB88410 (PubMed:9390560).Curated1

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.

Genome annotation databases

EnsemblBacteriaiCAS11489; CAS11489; E2348C_3941.
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.
RefSeqiWP_001339882.1. NC_011601.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CI9X-ray1.50L/M470-481[»]
2CIAX-ray1.45L472-481[»]
ProteinModelPortaliB7UM99.
SMRiB7UM99.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-27648N.
DIP-55921N.
IntActiB7UM99. 9 interactors.
MINTiMINT-7225953.

PTM databases

iPTMnetiB7UM99.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Phylogenomic databases

HOGENOMiHOG000059321.
KOiK12784.
OMAiQGIQSTY.

Miscellaneous databases

EvolutionaryTraceiB7UM99.

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.
ProtoNetiSearch...

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: November 2, 2016
This is version 56 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.