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
