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Database: UniProt
Entry: TIR_ECO57
LinkDB: TIR_ECO57
Original site: TIR_ECO57 
ID   TIR_ECO57               Reviewed;         558 AA.
AC   Q7DB77; Q7A9Q1; Q9R396;
DT   14-DEC-2011, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 106.
DE   RecName: Full=Translocated intimin receptor Tir;
DE   AltName: Full=Secreted effector protein Tir;
GN   Name=tir; Synonyms=espE; OrderedLocusNames=Z5112, ECs4561;
OS   Escherichia coli O157:H7.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83334;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX   PubMed=9673266; DOI=10.1128/iai.66.8.3810-3817.1998;
RA   Perna N.T., Mayhew G.F., Posfai G., Elliott S., Donnenberg M.S.,
RA   Kaper J.B., Blattner F.R.;
RT   "Molecular evolution of a pathogenicity island from enterohemorrhagic
RT   Escherichia coli O157:H7.";
RL   Infect. Immun. 66:3810-3817(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION,
RP   INTERACTION WITH INTIMIN, DISRUPTION PHENOTYPE, AND LACK OF TYROSINE
RP   PHOSPHORYLATION.
RC   STRAIN=O157:H7 / 86-24 / EHEC;
RX   PubMed=10225900; DOI=10.1128/iai.67.5.2389-2398.1999;
RA   DeVinney R., Stein M., Reinscheid D., Abe A., Ruschkowski S., Finlay B.B.;
RT   "Enterohemorrhagic Escherichia coli O157:H7 produces Tir, which is
RT   translocated to the host cell membrane but is not tyrosine
RT   phosphorylated.";
RL   Infect. Immun. 67:2389-2398(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=O157:H7 / 71074;
RA   Zhang Y., Golds G., John S.J., Laing C.R., Gannon V.P.J.;
RL   Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX   PubMed=11206551; DOI=10.1038/35054089;
RA   Perna N.T., Plunkett G. III, Burland V., Mau B., Glasner J.D., Rose D.J.,
RA   Mayhew G.F., Evans P.S., Gregor J., Kirkpatrick H.A., Posfai G.,
RA   Hackett J., Klink S., Boutin A., Shao Y., Miller L., Grotbeck E.J.,
RA   Davis N.W., Lim A., Dimalanta E.T., Potamousis K., Apodaca J.,
RA   Anantharaman T.S., Lin J., Yen G., Schwartz D.C., Welch R.A.,
RA   Blattner F.R.;
RT   "Genome sequence of enterohaemorrhagic Escherichia coli O157:H7.";
RL   Nature 409:529-533(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=O157:H7 / Sakai / RIMD 0509952 / EHEC;
RX   PubMed=11258796; DOI=10.1093/dnares/8.1.11;
RA   Hayashi T., Makino K., Ohnishi M., Kurokawa K., Ishii K., Yokoyama K.,
RA   Han C.-G., Ohtsubo E., Nakayama K., Murata T., Tanaka M., Tobe T., Iida T.,
RA   Takami H., Honda T., Sasakawa C., Ogasawara N., Yasunaga T., Kuhara S.,
RA   Shiba T., Hattori M., Shinagawa H.;
RT   "Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and
RT   genomic comparison with a laboratory strain K-12.";
RL   DNA Res. 8:11-22(2001).
RN   [6]
RP   SUBCELLULAR LOCATION, AND LACK OF TYROSINE PHOSPHORYLATION.
RC   STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX   PubMed=9632251; DOI=10.1046/j.1365-2958.1998.00798.x;
RA   Deibel C., Kramer S., Chakraborty T., Ebel F.;
RT   "EspE, a novel secreted protein of attaching and effacing bacteria, is
RT   directly translocated into infected host cells, where it appears as a
RT   tyrosine-phosphorylated 90 kDa protein.";
RL   Mol. Microbiol. 28:463-474(1998).
RN   [7]
RP   INTERACTION WITH INTIMIN.
RC   STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX   PubMed=10540286; DOI=10.1046/j.1365-2958.1999.01574.x;
RA   Liu H., Magoun L., Luperchio S., Schauer D.B., Leong J.M.;
RT   "The Tir-binding region of enterohaemorrhagic Escherichia coli intimin is
RT   sufficient to trigger actin condensation after bacterial-induced host cell
RT   signalling.";
RL   Mol. Microbiol. 34:67-81(1999).
RN   [8]
RP   FUNCTION.
RC   STRAIN=O157:H7 / 86-24 / EHEC, and O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX   PubMed=14764108; DOI=10.1111/j.1462-5822.2004.00364.x;
RA   Lommel S., Benesch S., Rohde M., Wehland J., Rottner K.;
RT   "Enterohaemorrhagic and enteropathogenic Escherichia coli use different
RT   mechanisms for actin pedestal formation that converge on N-WASP.";
RL   Cell. Microbiol. 6:243-254(2004).
RN   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND PHOSPHORYLATION.
RC   STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX   PubMed=16922867; DOI=10.1111/j.1462-5822.2006.00728.x;
RA   Campellone K.G., Brady M.J., Alamares J.G., Rowe D.C., Skehan B.M.,
RA   Tipper D.J., Leong J.M.;
RT   "Enterohaemorrhagic Escherichia coli Tir requires a C-terminal 12-residue
RT   peptide to initiate EspF-mediated actin assembly and harbours N-terminal
RT   sequences that influence pedestal length.";
RL   Cell. Microbiol. 8:1488-1503(2006).
RN   [10]
RP   FUNCTION, AND MUTAGENESIS OF GLY-452; THR-453; VAL-454; GLN-455; ASN-456;
RP   PRO-457; TYR-458; ALA-459; ASP-460; VAL-461; LYS-462 AND THR-463.
RC   STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX   PubMed=17521329; DOI=10.1111/j.1462-5822.2007.00954.x;
RA   Brady M.J., Campellone K.G., Ghildiyal M., Leong J.M.;
RT   "Enterohaemorrhagic and enteropathogenic Escherichia coli Tir proteins
RT   trigger a common Nck-independent actin assembly pathway.";
RL   Cell. Microbiol. 9:2242-2253(2007).
RN   [11]
RP   INTERACTION WITH HOST BAIAP2 AND BAIAP2L1.
RC   STRAIN=O157:H7 / 86-24 / EHEC, and O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX   PubMed=19286134; DOI=10.1016/j.chom.2009.02.003;
RA   Weiss S.M., Ladwein M., Schmidt D., Ehinger J., Lommel S., Stading K.,
RA   Beutling U., Disanza A., Frank R., Jansch L., Scita G., Gunzer F.,
RA   Rottner K., Stradal T.E.;
RT   "IRSp53 links the enterohemorrhagic E. coli effectors Tir and EspFU for
RT   actin pedestal formation.";
RL   Cell Host Microbe 5:244-258(2009).
RN   [12]
RP   REVIEW.
RX   PubMed=20477869; DOI=10.1111/j.1742-4658.2010.07653.x;
RA   Campellone K.G.;
RT   "Cytoskeleton-modulating effectors of enteropathogenic and
RT   enterohaemorrhagic Escherichia coli: Tir, EspFU and actin pedestal
RT   assembly.";
RL   FEBS J. 277:2390-2402(2010).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 269-336.
RC   STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RA   Ma Y., Zou Q., Gao G.F.;
RT   "Structural insight into the interaction between intimin and Tir of
RT   enterohaemorrhagic E coli: evidence for a dynamic sequential clustering-
RT   aggregating-reticulating model.";
RL   Submitted (DEC-2008) to the PDB data bank.
CC   -!- FUNCTION: Multifunctional protein that is required for efficient
CC       pedestal formation in host epithelial cells during infection. The
CC       extracellular region acts as a receptor for bacterial intimin, allowing
CC       the bacterium to attach tightly to the host-cell surface.
CC       Simultaneously, the intracellular region initiates a signaling cascade
CC       in the host cell, which leads to actin polymerization and formation of
CC       actin pedestals at the sites of bacterial adhesion. In strain EDL933,
CC       acts via the effector protein EspF(U), in a phosphotyrosine- and NCK-
CC       independent manner. Tir binds to host BAIAP2, which mediates
CC       association with EspF(U) and leads to stimulation of actin
CC       polymerization. {ECO:0000269|PubMed:10225900,
CC       ECO:0000269|PubMed:14764108, ECO:0000269|PubMed:16922867,
CC       ECO:0000269|PubMed:17521329}.
CC   -!- SUBUNIT: Interacts with intimin. Interacts with host BAIAP2 and
CC       BAIAP2L1. {ECO:0000269|PubMed:10225900, ECO:0000269|PubMed:10540286,
CC       ECO:0000269|PubMed:19286134}.
CC   -!- INTERACTION:
CC       Q7DB77; P58233: cesT; NbExp=2; IntAct=EBI-6480811, EBI-6403832;
CC       Q7DB77; Q7DB79: sepL; NbExp=4; IntAct=EBI-6480811, EBI-6403821;
CC       Q7DB77; P07355: ANXA2; Xeno; NbExp=2; IntAct=EBI-6480811, EBI-352622;
CC       Q7DB77; P49407: ARRB1; Xeno; NbExp=3; IntAct=EBI-6480811, EBI-743313;
CC       Q7DB77; Q9UQB8: BAIAP2; Xeno; NbExp=3; IntAct=EBI-6480811, EBI-525456;
CC       Q7DB77; Q9UQB8-4: BAIAP2; Xeno; NbExp=5; IntAct=EBI-6480811, EBI-6174091;
CC       Q7DB77; Q9UHR4: BAIAP2L1; Xeno; NbExp=3; IntAct=EBI-6480811, EBI-2483278;
CC       Q7DB77; Q60598: Cttn; Xeno; NbExp=4; IntAct=EBI-6480811, EBI-397955;
CC       Q7DB77; P37235: HPCAL1; Xeno; NbExp=3; IntAct=EBI-6480811, EBI-749311;
CC       Q7DB77; Q9UM19: HPCAL4; Xeno; NbExp=3; IntAct=EBI-6480811, EBI-744820;
CC       Q7DB77; P61601: NCALD; Xeno; NbExp=3; IntAct=EBI-6480811, EBI-749635;
CC       Q7DB77; O43924: PDE6D; Xeno; NbExp=3; IntAct=EBI-6480811, EBI-712685;
CC       Q7DB77; P29350: PTPN6; Xeno; NbExp=2; IntAct=EBI-6480811, EBI-78260;
CC       Q7DB77; O75716: STK16; Xeno; NbExp=3; IntAct=EBI-6480811, EBI-749295;
CC   -!- SUBCELLULAR LOCATION: Secreted. Host cell membrane; Multi-pass membrane
CC       protein. Note=Secreted via the type III secretion system (TTSS).
CC       Released into the host cytoplasm via TTSS and then independently
CC       inserts into the plasma membrane from a cytoplasmic location. In host
CC       cells, localizes to the tip of the actin pedestal.
CC   -!- DOMAIN: The intracellular N-terminal region contributes to the
CC       initiation of actin assembly and influences pedestal length. The
CC       central extracellular region is involved in bacterial intimin binding.
CC       The intracellular C-terminal region is required for initiation of actin
CC       pedestal formation. {ECO:0000269|PubMed:16922867}.
CC   -!- PTM: Phosphorylated by host kinases. {ECO:0000269|PubMed:16922867}.
CC   -!- DISRUPTION PHENOTYPE: Mutants show reduced bacterial adherence to host
CC       cells, and a loss of actin condensation beneath bacteria.
CC       {ECO:0000269|PubMed:10225900}.
CC   -!- SIMILARITY: Belongs to the Tir receptor family. {ECO:0000305}.
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DR   EMBL; AF071034; AAC31506.1; -; Genomic_DNA.
DR   EMBL; AF125993; AAD29391.1; -; Genomic_DNA.
DR   EMBL; GQ338312; ACU09451.1; -; Genomic_DNA.
DR   EMBL; AE005174; AAG58825.1; -; Genomic_DNA.
DR   EMBL; BA000007; BAB37984.1; -; Genomic_DNA.
DR   PIR; A98199; A98199.
DR   PIR; E86045; E86045.
DR   RefSeq; NP_312588.1; NC_002695.1.
DR   RefSeq; WP_001301454.1; NZ_SWKA01000005.1.
DR   PDB; 2ZQK; X-ray; 2.80 A; C/D/M/N=269-336.
DR   PDB; 2ZWK; X-ray; 3.10 A; B/D/F=274-336.
DR   PDBsum; 2ZQK; -.
DR   PDBsum; 2ZWK; -.
DR   AlphaFoldDB; Q7DB77; -.
DR   SMR; Q7DB77; -.
DR   IntAct; Q7DB77; 15.
DR   MINT; Q7DB77; -.
DR   STRING; 155864.EDL933_4949; -.
DR   EnsemblBacteria; AAG58825; AAG58825; Z5112.
DR   EnsemblBacteria; BAB37984; BAB37984; ECs_4561.
DR   GeneID; 915465; -.
DR   KEGG; ece:Z5112; -.
DR   KEGG; ecs:ECs_4561; -.
DR   PATRIC; fig|386585.9.peg.4778; -.
DR   eggNOG; ENOG5033PQE; Bacteria.
DR   HOGENOM; CLU_497576_0_0_6; -.
DR   OMA; QGIQSTY; -.
DR   EvolutionaryTrace; Q7DB77; -.
DR   Proteomes; UP000000558; Chromosome.
DR   Proteomes; UP000002519; Chromosome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   Gene3D; 4.10.820.10; -; 1.
DR   InterPro; IPR037003; Tir_central_sf.
DR   InterPro; IPR022638; Transloc_intimin_rcpt.
DR   InterPro; IPR022639; Transloc_intimin_rcpt_C.
DR   InterPro; IPR003536; Transloc_intimin_rcpt_cen_dom.
DR   InterPro; IPR022633; Transloc_intimin_rcpt_N.
DR   Pfam; PF07489; Tir_receptor_C; 1.
DR   Pfam; PF03549; Tir_receptor_M; 1.
DR   Pfam; PF07490; Tir_receptor_N; 1.
DR   PRINTS; PR01370; TRNSINTIMINR.
PE   1: Evidence at protein level;
KW   3D-structure; Host cell membrane; Host membrane; Membrane; Phosphoprotein;
KW   Receptor; Reference proteome; Secreted; Transmembrane; Transmembrane helix;
KW   Virulence.
FT   CHAIN           1..558
FT                   /note="Translocated intimin receptor Tir"
FT                   /id="PRO_0000414051"
FT   TOPO_DOM        1..230
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        231..251
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        252..362
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        363..383
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        384..558
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..44
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          182..226
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          257..280
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          388..451
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          533..558
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           456..458
FT                   /note="Essential for actin pedestal formation"
FT   COMPBIAS        30..44
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        206..226
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        258..280
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        537..552
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         452
FT                   /note="G->A: Does not affect translocation into the host
FT                   cell, ability to bind intimin and pedestal formation."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         453
FT                   /note="T->A: Does not affect translocation into the host
FT                   cell, ability to bind intimin and pedestal formation."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         454
FT                   /note="V->A: Does not affect translocation into the host
FT                   cell, ability to bind intimin and pedestal formation."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         455
FT                   /note="Q->A: Does not affect translocation into the host
FT                   cell, ability to bind intimin and pedestal formation."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         456
FT                   /note="N->A: Strong decrease in pedestal formation. Does
FT                   not affect translocation into the host cell and ability to
FT                   bind intimin."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         457
FT                   /note="P->A: Strong decrease in pedestal formation. Does
FT                   not affect translocation into the host cell and ability to
FT                   bind intimin."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         458
FT                   /note="Y->A: Strong decrease in pedestal formation. Does
FT                   not affect translocation into the host cell and ability to
FT                   bind intimin."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         458
FT                   /note="Y->F: Slight decrease in pedestal formation. Does
FT                   not affect translocation into the host cell and ability to
FT                   bind intimin."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         459
FT                   /note="A->G: Does not affect translocation into the host
FT                   cell, ability to bind intimin and pedestal formation."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         460
FT                   /note="D->A: Does not affect translocation into the host
FT                   cell, ability to bind intimin and pedestal formation."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         461
FT                   /note="V->A: Does not affect translocation into the host
FT                   cell, ability to bind intimin and pedestal formation."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         462
FT                   /note="K->A: Does not affect translocation into the host
FT                   cell, ability to bind intimin and pedestal formation."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   MUTAGEN         463
FT                   /note="T->A: Does not affect translocation into the host
FT                   cell, ability to bind intimin and pedestal formation."
FT                   /evidence="ECO:0000269|PubMed:17521329"
FT   HELIX           274..288
FT                   /evidence="ECO:0007829|PDB:2ZQK"
FT   HELIX           291..293
FT                   /evidence="ECO:0007829|PDB:2ZQK"
FT   STRAND          294..298
FT                   /evidence="ECO:0007829|PDB:2ZQK"
FT   STRAND          304..310
FT                   /evidence="ECO:0007829|PDB:2ZQK"
FT   HELIX           312..334
FT                   /evidence="ECO:0007829|PDB:2ZQK"
SQ   SEQUENCE   558 AA;  58022 MW;  99C417222D4B4AA1 CRC64;
     MPIGNLGHNP NVNNSIPPAP PLPSQTDGAG GRGQLINSTG PLGSRALFTP VRNSMADSGD
     NRASDVPGLP VNPMRLAASE ITLNDGFEVL HDHGPLDTLN RQIGSSVFRV ETQEDGKHIA
     VGQRNGVETS VVLSDQEYAR LQSIDPEGKD KFVFTGGRGG AGHAMVTVAS DITEARQRIL
     ELLEPKGTGE SKGAGESKGV GELRESNSGA ENTTETQTST STSSLRSDPK LWLALGTVAT
     GLIGLAATGI VQALALTPEP DSPTTTDPDA AASATETATR DQLTKEAFQN PDNQKVNIDE
     LGNAIPSGVL KDDVVANIEE QAKAAGEEAK QQAIENNAQA QKKYDEQQAK RQEELKVSSG
     AGYGLSGALI LGGGIGVAVT AALHRKNQPV EQTTTTTTTT TTTSARTVEN KPANNTPAQG
     NVDTPGSEDT MESRRSSMAS TSSTFFDTSS IGTVQNPYAD VKTSLHDSQV PTSNSNTSVQ
     NMGNTDSVVY STIQHPPRDT TDNGARLLGN PSAGIQSTYA RLALSGGLRH DMGGLTGGSN
     SAVNTSNNPP APGSHRFV
//
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