TIR_ECO27
ID TIR_ECO27 Reviewed; 550 AA.
AC B7UM99; O50190; O52147;
DT 14-DEC-2011, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 1.
DT 25-MAY-2022, entry version 72.
DE RecName: Full=Translocated intimin receptor Tir;
DE AltName: Full=Secreted effector protein Tir;
GN Name=tir; Synonyms=espE; OrderedLocusNames=E2348C_3941;
OS Escherichia coli O127:H6 (strain E2348/69 / EPEC).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=574521;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-31, FUNCTION,
RP INTERACTION WITH INTIMIN, SUBCELLULAR LOCATION, SECRETION VIA TYPE III
RP SECRETION SYSTEM, PHOSPHORYLATION, AND GENE NAME.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=9390560; DOI=10.1016/s0092-8674(00)80437-7;
RA Kenny B., DeVinney R., Stein M., Reinscheid D.J., Frey E.A., Finlay B.B.;
RT "Enteropathogenic E. coli (EPEC) transfers its receptor for intimate
RT adherence into mammalian cells.";
RL Cell 91:511-520(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=E2348/69 / EPEC;
RX PubMed=9593291; DOI=10.1046/j.1365-2958.1998.00783.x;
RA Elliott S.J., Wainwright L.A., McDaniel T.K., Jarvis K.G., Deng Y.K.,
RA Lai L.C., McNamara B.P., Donnenberg M.S., Kaper J.B.;
RT "The complete sequence of the locus of enterocyte effacement (LEE) from
RT enteropathogenic Escherichia coli E2348/69.";
RL Mol. Microbiol. 28:1-4(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=E2348/69 / EPEC;
RX PubMed=18952797; DOI=10.1128/jb.01238-08;
RA Iguchi A., Thomson N.R., Ogura Y., Saunders D., Ooka T., Henderson I.R.,
RA Harris D., Asadulghani M., Kurokawa K., Dean P., Kenny B., Quail M.A.,
RA Thurston S., Dougan G., Hayashi T., Parkhill J., Frankel G.;
RT "Complete genome sequence and comparative genome analysis of
RT enteropathogenic Escherichia coli O127:H6 strain E2348/69.";
RL J. Bacteriol. 191:347-354(2009).
RN [4]
RP SUBCELLULAR LOCATION.
RC STRAIN=E2348/69 / EPEC;
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 [5]
RP INTERACTION WITH INTIMIN.
RC STRAIN=E2348/69 / EPEC;
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, INTERACTION WITH INTIMIN,
RP PHOSPHORYLATION, AND MUTAGENESIS OF TYR-474 AND TYR-483.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=10096089; DOI=10.1046/j.1365-2958.1999.01265.x;
RA Kenny B.;
RT "Phosphorylation of tyrosine 474 of the enteropathogenic Escherichia coli
RT (EPEC) Tir receptor molecule is essential for actin nucleating activity and
RT is preceded by additional host modifications.";
RL Mol. Microbiol. 31:1229-1241(1999).
RN [7]
RP INTERACTION WITH HOST ALPHA-ACTININ, AND DOMAIN.
RC STRAIN=EPEC;
RX PubMed=10873808; DOI=10.1016/s0960-9822(00)00543-1;
RA Goosney D.L., DeVinney R., Pfuetzner R.A., Frey E.A., Strynadka N.C.,
RA Finlay B.B.;
RT "Enteropathogenic E. coli translocated intimin receptor, Tir, interacts
RT directly with alpha-actinin.";
RL Curr. Biol. 10:735-738(2000).
RN [8]
RP INTERACTION WITH HOST NCK.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=11533668; DOI=10.1038/ncb0901-856;
RA Gruenheid S., DeVinney R., Bladt F., Goosney D., Gelkop S., Gish G.D.,
RA Pawson T., Finlay B.B.;
RT "Enteropathogenic E. coli Tir binds Nck to initiate actin pedestal
RT formation in host cells.";
RL Nat. Cell Biol. 3:856-859(2001).
RN [9]
RP INTERACTION WITH HOST NCK, PHOSPHORYLATION, AND MUTAGENESIS OF TYR-474.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=11918809; DOI=10.1046/j.1365-2958.2002.02817.x;
RA Campellone K.G., Giese A., Tipper D.J., Leong J.M.;
RT "A tyrosine-phosphorylated 12-amino-acid sequence of enteropathogenic
RT Escherichia coli Tir binds the host adaptor protein Nck and is required for
RT Nck localization to actin pedestals.";
RL Mol. Microbiol. 43:1227-1241(2002).
RN [10]
RP FUNCTION.
RC STRAIN=E2348/69 / EPEC;
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 [11]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH INTIMIN AND HOST NCK,
RP PHOSPHORYLATION, AND DOMAIN.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=14757753; DOI=10.1083/jcb.200306032;
RA Campellone K.G., Rankin S., Pawson T., Kirschner M.W., Tipper D.J.,
RA Leong J.M.;
RT "Clustering of Nck by a 12-residue Tir phosphopeptide is sufficient to
RT trigger localized actin assembly.";
RL J. Cell Biol. 164:407-416(2004).
RN [12]
RP FUNCTION, INTERACTION WITH HOST NCK, PHOSPHORYLATION AT TYR-454 AND
RP TYR-474, AND MUTAGENESIS OF TYR-454 AND TYR-474.
RC STRAIN=E2348/69 / EPEC;
RX PubMed=15813734; DOI=10.1111/j.1365-2958.2005.04558.x;
RA Campellone K.G., Leong J.M.;
RT "Nck-independent actin assembly is mediated by two phosphorylated tyrosines
RT within enteropathogenic Escherichia coli Tir.";
RL Mol. Microbiol. 56:416-432(2005).
RN [13]
RP SUBCELLULAR LOCATION.
RC STRAIN=EPEC;
RX PubMed=16436373; DOI=10.1074/jbc.m513532200;
RA Race P.R., Lakey J.H., Banfield M.J.;
RT "Insertion of the enteropathogenic Escherichia coli Tir virulence protein
RT into membranes in vitro.";
RL J. Biol. Chem. 281:7842-7849(2006).
RN [14]
RP FUNCTION, AND MUTAGENESIS OF ASN-452; PRO-453; TYR-454 AND TYR-474.
RC STRAIN=E2348/69 / EPEC;
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 [15]
RP INTERACTION WITH HOST BAIAP2.
RC STRAIN=E2348/69 / EPEC;
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 [16]
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 [17]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 472-481 IN COMPLEX WITH NCK1 AND
RP NCK2, AND PHOSPHORYLATION AT TYR-474.
RX PubMed=16636066; DOI=10.1074/jbc.m512917200;
RA Frese S., Schubert W.D., Findeis A.C., Marquardt T., Roske Y.S.,
RA Stradal T.E., Heinz D.W.;
RT "The phosphotyrosine peptide binding specificity of Nck1 and Nck2 Src
RT homology 2 domains.";
RL J. Biol. Chem. 281:18236-18245(2006).
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 E2348/69,
CC acts mainly via the host adaptor proteins NCK1 and NCK2. Once clustered
CC and phosphorylated at Tyr-474, Tir binds to NCK proteins, which in turn
CC bind and activate host WASL/N-WASP, leading to actin polymerization.
CC Can also trigger an inefficient, NCK-independent pedestal formation.
CC This pathway involves phosphorylation of Tyr-454 and probably a
CC putative host adaptor. Acts also via direct binding to the host
CC cytoskeletal protein alpha-actinin in a NCK- and phosphotyrosine-
CC independent manner. This interaction may stabilize the pedestal, but is
CC not essential for its formation. {ECO:0000269|PubMed:10096089,
CC ECO:0000269|PubMed:14757753, ECO:0000269|PubMed:14764108,
CC ECO:0000269|PubMed:15813734, ECO:0000269|PubMed:17521329,
CC ECO:0000269|PubMed:9390560}.
CC -!- SUBUNIT: Interacts with intimin. Interacts with host proteins NCK1,
CC NCK2, alpha-actinin and BAIAP2. {ECO:0000269|PubMed:10096089,
CC ECO:0000269|PubMed:10225900, ECO:0000269|PubMed:10873808,
CC ECO:0000269|PubMed:11533668, ECO:0000269|PubMed:11918809,
CC ECO:0000269|PubMed:14757753, ECO:0000269|PubMed:15813734,
CC ECO:0000269|PubMed:16636066, ECO:0000269|PubMed:19286134,
CC ECO:0000269|PubMed:9390560}.
CC -!- INTERACTION:
CC B7UM99; P21244: cesT; NbExp=6; IntAct=EBI-2504426, EBI-2504434;
CC B7UM99; P07355: ANXA2; Xeno; NbExp=3; IntAct=EBI-2504426, EBI-352622;
CC B7UM99; Q9UQB8-4: BAIAP2; Xeno; NbExp=3; IntAct=EBI-2504426, EBI-6174091;
CC B7UM99; Q14247: CTTN; Xeno; NbExp=3; IntAct=EBI-2504426, EBI-351886;
CC B7UM99; P05783: KRT18; Xeno; NbExp=5; IntAct=EBI-2504426, EBI-297888;
CC B7UM99; P29350: PTPN6; Xeno; NbExp=4; IntAct=EBI-2504426, EBI-78260;
CC B7UM99; P29351: Ptpn6; Xeno; NbExp=2; IntAct=EBI-2504426, EBI-2620699;
CC B7UM99; P31946: YWHAB; Xeno; NbExp=2; IntAct=EBI-2504426, EBI-359815;
CC B7UM99; P27348: YWHAQ; Xeno; NbExp=6; IntAct=EBI-2504426, EBI-359854;
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 interacts with host alpha-
CC actinin and is not required for pedestal formation. The central
CC extracellular region (amino acids 277-332) is involved in bacterial
CC intimin binding. The intracellular C-terminal region binds to host NCK.
CC {ECO:0000269|PubMed:10096089, ECO:0000269|PubMed:10873808,
CC ECO:0000269|PubMed:14757753}.
CC -!- PTM: Phosphorylated on Tyr-474 by host kinases. Tyr-454 can also be
CC phosphorylated, although at lower efficiency. Phosphorylation is
CC stimulated by clustering of Tir by intimin.
CC {ECO:0000269|PubMed:10096089, ECO:0000269|PubMed:11918809,
CC ECO:0000269|PubMed:14757753, ECO:0000269|PubMed:15813734,
CC ECO:0000269|PubMed:16636066, ECO:0000269|PubMed:9390560}.
CC -!- SIMILARITY: Belongs to the Tir receptor family. {ECO:0000305}.
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DR EMBL; AF013122; AAB88410.1; -; Genomic_DNA.
DR EMBL; AF022236; AAC38390.1; -; Genomic_DNA.
DR EMBL; FM180568; CAS11489.1; -; Genomic_DNA.
DR RefSeq; WP_001339882.1; NC_011601.1.
DR PDB; 2CI9; X-ray; 1.50 A; L/M=470-481.
DR PDB; 2CIA; X-ray; 1.45 A; L=472-481.
DR PDBsum; 2CI9; -.
DR PDBsum; 2CIA; -.
DR AlphaFoldDB; B7UM99; -.
DR SASBDB; B7UM99; -.
DR SMR; B7UM99; -.
DR DIP; DIP-27648N; -.
DR DIP; DIP-55921N; -.
DR IntAct; B7UM99; 18.
DR MINT; B7UM99; -.
DR iPTMnet; B7UM99; -.
DR EnsemblBacteria; CAS11489; CAS11489; E2348C_3941.
DR KEGG; ecg:E2348C_3941; -.
DR HOGENOM; CLU_497576_0_0_6; -.
DR OMA; QGIQSTY; -.
DR EvolutionaryTrace; B7UM99; -.
DR Proteomes; UP000008205; 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; Direct protein sequencing; Host cell membrane; Host membrane;
KW Membrane; Phosphoprotein; Receptor; Secreted; Transmembrane;
KW Transmembrane helix; Virulence.
FT CHAIN 1..550
FT /note="Translocated intimin receptor Tir"
FT /id="PRO_0000414050"
FT TOPO_DOM 1..233
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 234..254
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 255..362
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 363..383
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 384..550
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 260..285
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 332..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..449
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 452..454
FT /note="Essential for NCK-independent actin pedestal
FT formation"
FT COMPBIAS 214..228
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 266..285
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 389..419
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 431..449
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 454
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15813734"
FT MOD_RES 474
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15813734,
FT ECO:0000269|PubMed:16636066"
FT MUTAGEN 452
FT /note="N->A: Lack of pedestal formation; when associated
FT with F-474."
FT /evidence="ECO:0000269|PubMed:17521329"
FT MUTAGEN 453
FT /note="P->A: Lack of pedestal formation; when associated
FT with F-474."
FT /evidence="ECO:0000269|PubMed:17521329"
FT MUTAGEN 454
FT /note="Y->A: Lack of pedestal formation; when associated
FT with F-474."
FT /evidence="ECO:0000269|PubMed:15813734,
FT ECO:0000269|PubMed:17521329"
FT MUTAGEN 454
FT /note="Y->F: Does not inhibit translocation into the host
FT cell. Almost no change in actin polymerization. Lack of
FT pedestal formation; when associated with F-474."
FT /evidence="ECO:0000269|PubMed:15813734,
FT ECO:0000269|PubMed:17521329"
FT MUTAGEN 474
FT /note="Y->D,E: Loss of phosphorylation and strong decrease
FT in actin polymerization."
FT /evidence="ECO:0000269|PubMed:10096089,
FT ECO:0000269|PubMed:11918809, ECO:0000269|PubMed:15813734,
FT ECO:0000269|PubMed:17521329"
FT MUTAGEN 474
FT /note="Y->F: Loss of phosphorylation and strong decrease in
FT actin polymerization. Lack of pedestal formation; when
FT associated with F-454."
FT /evidence="ECO:0000269|PubMed:10096089,
FT ECO:0000269|PubMed:11918809, ECO:0000269|PubMed:15813734,
FT ECO:0000269|PubMed:17521329"
FT MUTAGEN 474
FT /note="Y->S: Does not inhibit translocation into the host
FT cell. Loss of phosphorylation and strong decrease in actin
FT polymerization."
FT /evidence="ECO:0000269|PubMed:10096089,
FT ECO:0000269|PubMed:11918809, ECO:0000269|PubMed:15813734,
FT ECO:0000269|PubMed:17521329"
FT MUTAGEN 483
FT /note="Y->S: Does not inhibit translocation into the host
FT cell."
FT /evidence="ECO:0000269|PubMed:10096089"
FT CONFLICT 412..430
FT /note="NTPAQGGTDATRAEDASLN -> IPQHKVALMPQERRRFSD (in Ref.
FT 1; AAB88410)"
FT /evidence="ECO:0000305"
FT CONFLICT 533
FT /note="S -> T (in Ref. 1; AAB88410)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 550 AA; 56510 MW; 19DD08A9BE9251CB CRC64;
MPIGNLGNNV NGNHLIPPAP PLPSQTDGAA RGGTGHLISS TGALGSRSLF SPLRNSMADS
VDSRDIPGLP TNPSRLAAAT SETCLLGGFE VLHDKGPLDI LNTQIGPSAF RVEVQADGTH
AAIGEKNGLE VSVTLSPQEW SSLQSIDTEG KNRFVFTGGR GGSGHPMVTV ASDIAEARTK
ILAKLDPDNH GGRQPKDVDT RSVGVGSASG IDDGVVSETH TSTTNSSVRS DPKFWVSVGA
IAAGLAGLAA TGIAQALALT PEPDDPTTTD PDQAANAAES ATKDQLTQEA FKNPENQKVN
IDANGNAIPS GELKDDIVEQ IAQQAKEAGE VARQQAVESN AQAQQRYEDQ HARRQEELQL
SSGIGYGLSS ALIVAGGIGA GVTTALHRRN QPAEQTTTTT THTVVQQQTG GNTPAQGGTD
ATRAEDASLN RRDSQGSVAS THWSDSSSEV VNPYAEVGGA RNSLSAHQPE EHIYDEVAAD
PGYSVIQNFS GSGPVTGRLI GTPGQGIQST YALLANSGGL RLGMGGLTSG GESAVSSVNA
APTPGPVRFV
