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B7UM99 (TIR_ECO27) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 38. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Translocated intimin receptor Tir
Alternative name(s):
Secreted effector protein Tir
Gene names
Name:tir
Synonyms:espE
Ordered Locus Names:E2348C_3941
OrganismEscherichia coli O127:H6 (strain E2348/69 / EPEC) [Complete proteome] [HAMAP]
Taxonomic identifier574521 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length550 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.6 Ref.10 Ref.11 Ref.12 Ref.14

Subunit structure

Interacts with intimin. Interacts with host proteins NCK1, NCK2, alpha-actinin and BAIAP2. Ref.1 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.15

Subcellular location

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. Ref.1 Ref.4 Ref.6 Ref.11 Ref.13

Domain

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. Ref.6 Ref.7 Ref.11

Post-translational modification

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. Ref.1 Ref.6 Ref.9 Ref.11 Ref.12 Ref.17

Sequence similarities

Belongs to the Tir receptor family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 550550Translocated intimin receptor Tir
PRO_0000414050

Regions

Topological domain1 – 233233Cytoplasmic Potential
Transmembrane234 – 25421Helical; Potential
Topological domain255 – 362108Extracellular Potential
Transmembrane363 – 38321Helical; Potential
Topological domain384 – 550167Cytoplasmic Potential
Motif452 – 4543Essential for NCK-independent actin pedestal formation

Amino acid modifications

Modified residue4541Phosphotyrosine Ref.12
Modified residue4741Phosphotyrosine Ref.12 Ref.17

Experimental info

Mutagenesis4521N → A: Lack of pedestal formation; when associated with F-474. Ref.14
Mutagenesis4531P → A: Lack of pedestal formation; when associated with F-474. Ref.14
Mutagenesis4541Y → A: Lack of pedestal formation; when associated with F-474. Ref.12 Ref.14
Mutagenesis4541Y → F: Does not inhibit translocation into the host cell. Almost no change in actin polymerization. Lack of pedestal formation; when associated with F-474. Ref.12 Ref.14
Mutagenesis4741Y → D or E: Loss of phosphorylation and strong decrease in actin polymerization. Ref.6 Ref.9 Ref.12 Ref.14
Mutagenesis4741Y → F: Loss of phosphorylation and strong decrease in actin polymerization. Lack of pedestal formation; when associated with F-454. Ref.6 Ref.9 Ref.12 Ref.14
Mutagenesis4741Y → S: Does not inhibit translocation into the host cell. Loss of phosphorylation and strong decrease in actin polymerization. Ref.6 Ref.9 Ref.12 Ref.14
Mutagenesis4831Y → S: Does not inhibit translocation into the host cell. Ref.6
Sequence conflict412 – 43019NTPAQ…DASLN → IPQHKVALMPQERRRFSD in AAB88410. Ref.1
Sequence conflict5331S → T in AAB88410. Ref.1

Sequences

Sequence LengthMass (Da)Tools
B7UM99 [UniParc].

Last modified February 10, 2009. Version 1.
Checksum: 19DD08A9BE9251CB

FASTA55056,510
        10         20         30         40         50         60 
MPIGNLGNNV NGNHLIPPAP PLPSQTDGAA RGGTGHLISS TGALGSRSLF SPLRNSMADS 

        70         80         90        100        110        120 
VDSRDIPGLP TNPSRLAAAT SETCLLGGFE VLHDKGPLDI LNTQIGPSAF RVEVQADGTH 

       130        140        150        160        170        180 
AAIGEKNGLE VSVTLSPQEW SSLQSIDTEG KNRFVFTGGR GGSGHPMVTV ASDIAEARTK 

       190        200        210        220        230        240 
ILAKLDPDNH GGRQPKDVDT RSVGVGSASG IDDGVVSETH TSTTNSSVRS DPKFWVSVGA 

       250        260        270        280        290        300 
IAAGLAGLAA TGIAQALALT PEPDDPTTTD PDQAANAAES ATKDQLTQEA FKNPENQKVN 

       310        320        330        340        350        360 
IDANGNAIPS GELKDDIVEQ IAQQAKEAGE VARQQAVESN AQAQQRYEDQ HARRQEELQL 

       370        380        390        400        410        420 
SSGIGYGLSS ALIVAGGIGA GVTTALHRRN QPAEQTTTTT THTVVQQQTG GNTPAQGGTD 

       430        440        450        460        470        480 
ATRAEDASLN RRDSQGSVAS THWSDSSSEV VNPYAEVGGA RNSLSAHQPE EHIYDEVAAD 

       490        500        510        520        530        540 
PGYSVIQNFS GSGPVTGRLI GTPGQGIQST YALLANSGGL RLGMGGLTSG GESAVSSVNA 

       550 
APTPGPVRFV 

« Hide

References

« Hide 'large scale' references
[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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF013122 Genomic DNA. Translation: AAB88410.1.
AF022236 Genomic DNA. Translation: AAC38390.1.
FM180568 Genomic DNA. Translation: CAS11489.1.
RefSeqYP_002331403.1. NC_011601.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CI9X-ray1.50L/M470-481[»]
2CIAX-ray1.45L472-481[»]
ProteinModelPortalB7UM99.
SMRB7UM99. Positions 272-336.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-27648N.
DIP-55921N.
IntActB7UM99. 4 interactions.
MINTMINT-7225953.
STRING574521.E2348C_3941.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaCAS11489; CAS11489; E2348C_3941.
GeneID7064348.
KEGGecg:E2348C_3941.
PATRIC18347096. VBIEscCol90278_4031.

Organism-specific databases

CMRSearch...

Phylogenomic databases

HOGENOMHOG000059321.
KOK12784.
OMAQGIQSTY.
OrthoDBEOG63FVXM.

Enzyme and pathway databases

BioCycECOL574521:GJAO-4084-MONOMER.

Family and domain databases

Gene3D4.10.820.10. 1 hit.
InterProIPR022638. Transloc_intimin_rcpt.
IPR022639. Transloc_intimin_rcpt_C.
IPR003536. Transloc_intimin_rcpt_cen_dom.
IPR022633. Transloc_intimin_rcpt_N.
[Graphical view]
PfamPF07489. Tir_receptor_C. 1 hit.
PF03549. Tir_receptor_M. 1 hit.
PF07490. Tir_receptor_N. 1 hit.
[Graphical view]
PRINTSPR01370. TRNSINTIMINR.
ProtoNetSearch...

Other

EvolutionaryTraceB7UM99.

Entry information

Entry nameTIR_ECO27
AccessionPrimary (citable) accession number: B7UM99
Secondary accession number(s): O50190, O52147
Entry history
Integrated into UniProtKB/Swiss-Prot: December 14, 2011
Last sequence update: February 10, 2009
Last modified: June 11, 2014
This is version 38 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references