ID   DTXR_CORDI              Reviewed;         226 AA.
AC   P0DJL7; P33120; Q5XQ41; Q5XQ42; Q5XQ43;
DT   05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT   05-SEP-2012, sequence version 1.
DT   29-OCT-2014, entry version 18.
DE   RecName: Full=Diphtheria toxin repressor;
DE   AltName: Full=Iron-dependent diphtheria tox regulatory element;
DE   AltName: Full=Tox regulatory factor;
GN   Name=dtxR; OrderedLocusNames=DIP1414;
OS   Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype
OS   gravis).
OC   Bacteria; Actinobacteria; Actinobacteridae; Actinomycetales;
OC   Corynebacterineae; Corynebacteriaceae; Corynebacterium.
OX   NCBI_TaxID=257309;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=C7(-);
RX   PubMed=2116013; DOI=10.1073/pnas.87.15.5968;
RA   Boyd J.M., Oza M.N., Murphy J.R.;
RT   "Molecular cloning and DNA sequence analysis of a diphtheria tox iron-
RT   dependent regulatory element (dtxR) from Corynebacterium
RT   diphtheriae.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:5968-5972(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=1030(-), and C7hm723(-);
RX   PubMed=1735717;
RA   Boyd J.M., Hall K.C., Murphy J.R.;
RT   "DNA sequences and characterization of dtxR alleles from
RT   Corynebacterium diphtheriae PW8(-), 1030(-), and C7hm723(-).";
RL   J. Bacteriol. 174:1268-1272(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND STUDY OF FUNCTIONALITY.
RC   STRAIN=CD95/211-, CD95/305-, and CD95/407-;
RX   PubMed=15634975; DOI=10.1128/JCM.43.1.223-228.2005;
RA   De Zoysa A.S., Efstratiou A., Hawkey P.M.;
RT   "Molecular characterization of diphtheria toxin repressor (dtxR) genes
RT   present in nontoxigenic Corynebacterium diphtheriae strains isolated
RT   in the United Kingdom.";
RL   J. Clin. Microbiol. 43:223-228(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700971 / NCTC 13129 / Biotype gravis;
RX   PubMed=14602910; DOI=10.1093/nar/gkg874;
RA   Cerdeno-Tarraga A.-M., Efstratiou A., Dover L.G., Holden M.T.G.,
RA   Pallen M.J., Bentley S.D., Besra G.S., Churcher C.M., James K.D.,
RA   De Zoysa A., Chillingworth T., Cronin A., Dowd L., Feltwell T.,
RA   Hamlin N., Holroyd S., Jagels K., Moule S., Quail M.A.,
RA   Rabbinowitsch E., Rutherford K.M., Thomson N.R., Unwin L.,
RA   Whitehead S., Barrell B.G., Parkhill J.;
RT   "The complete genome sequence and analysis of Corynebacterium
RT   diphtheriae NCTC13129.";
RL   Nucleic Acids Res. 31:6516-6523(2003).
RN   [5]
RP   CHARACTERIZATION.
RX   PubMed=1502169; DOI=10.1073/pnas.89.16.7576;
RA   Schmitt M.P., Twiddy E.M., Holmes R.K.;
RT   "Purification and characterization of the diphtheria toxin
RT   repressor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:7576-7580(1992).
RN   [6]
RP   METAL-BINDING.
RX   PubMed=1400485;
RA   Tao X., Murphy J.R.;
RT   "Binding of the metalloregulatory protein DtxR to the diphtheria tox
RT   operator requires a divalent heavy metal ion and protects the
RT   palindromic sequence from DNase I digestion.";
RL   J. Biol. Chem. 267:21761-21764(1992).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX   PubMed=8823163; DOI=10.1021/bi960861d;
RA   Qiu X., Pohl E., Holmes R.K., Hol W.G.J.;
RT   "High-resolution structure of the diphtheria toxin repressor complexed
RT   with cobalt and manganese reveals an SH3-like third domain and
RT   suggests a possible role of phosphate as co-corepressor.";
RL   Biochemistry 35:12292-12302(1996).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX   PubMed=7568230; DOI=10.1073/pnas.92.21.9843;
RA   Schiering N., Tao X., Zeng H., Murphy J.R., Petsko G.A., Ringe D.;
RT   "Structures of the apo- and the metal ion-activated forms of the
RT   diphtheria tox repressor from Corynebacterium diphtheriae.";
RL   Proc. Natl. Acad. Sci. U.S.A. 92:9843-9850(1995).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX   PubMed=9697776; DOI=10.1038/28893;
RA   White A., Ding X., Vanderspek J.C., Murphy J.R., Ringe D.;
RT   "Structure of the metal-ion-activated diphtheria toxin repressor/tox
RT   operator complex.";
RL   Nature 394:502-506(1998).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX   PubMed=10085021;
RA   Goranson-Siekierke J., Pohl E., Hol W.G.J., Holmes R.K.;
RT   "Anion-coordinating residues at binding site 1 are essential for the
RT   biological activity of the diphtheria toxin repressor.";
RL   Infect. Immun. 67:1806-1811(1999).
RN   [11]
RP   STRUCTURE BY NMR OF 130-226.
RX   PubMed=10339551; DOI=10.1073/pnas.96.11.6119;
RA   Wang G., Wylie G.P., Twigg P.D., Caspar D.L.D., Murphy J.R.,
RA   Logan T.M.;
RT   "Solution structure and peptide binding studies of the C-terminal src
RT   homology 3-like domain of the diphtheria toxin repressor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:6119-6124(1999).
CC   -!- FUNCTION: Iron-binding repressor of the dipheteria toxin gene
CC       expression. May serve as a global regulator of gene expression.
CC       Represses ripA under iron excess.
CC   -!- SUBUNIT: Homodimer.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- MISCELLANEOUS: The N-terminal region may be involved in iron
CC       binding and may associate with the tox operator. Binding of dtxR
CC       to tox operator requires a divalent metal ion such as cobalt,
CC       ferric, manganese, and nickel ions whereas zinc ions show weak
CC       activation.
CC   -!- MISCELLANEOUS: The dtxR gene was functional in the non-toxygenic
CC       strains CD95/211-, CD95/305- and CD95/407- isolated in the United
CC       Kingdom. These findings demonstrate that, if lysogenised by a
CC       bacteriophage, non-toxygenic strains could produce toxin and
CC       therefore represent a potential reservoir for toxygenic
CC       C.diphtheriae.
CC   -!- SIMILARITY: Contains 1 HTH dtxR-type DNA-binding domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00296}.
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DR   EMBL; M34239; AAA23296.1; -; Genomic_DNA.
DR   EMBL; M80336; AAA23302.1; -; Genomic_DNA.
DR   EMBL; M80337; AAA23301.1; -; Genomic_DNA.
DR   EMBL; AY741368; AAU93781.1; -; Genomic_DNA.
DR   EMBL; AY741369; AAU93782.1; -; Genomic_DNA.
DR   EMBL; AY741370; AAU93783.1; -; Genomic_DNA.
DR   EMBL; BX248358; CAE49945.1; -; Genomic_DNA.
DR   PIR; A35968; A35968.
DR   RefSeq; NP_939766.1; NC_002935.2.
DR   RefSeq; WP_010935052.1; NC_002935.2.
DR   PDB; 1BI0; X-ray; 2.30 A; A=1-226.
DR   PDB; 1BI1; X-ray; 2.20 A; A=1-226.
DR   PDB; 1BI2; X-ray; 2.30 A; A/B=1-226.
DR   PDB; 1BI3; X-ray; 2.40 A; A/B=1-226.
DR   PDB; 1BYM; NMR; -; A=130-226.
DR   PDB; 1C0W; X-ray; 3.20 A; A/B/C/D=2-226.
DR   PDB; 1DDN; X-ray; 3.00 A; A/B/C/D=1-226.
DR   PDB; 1DPR; X-ray; 3.00 A; A/B=1-226.
DR   PDB; 1F5T; X-ray; 3.00 A; A/B/C/D=1-121.
DR   PDB; 1FWZ; X-ray; 2.30 A; A=1-226.
DR   PDB; 1G3S; X-ray; 2.40 A; A=1-226.
DR   PDB; 1G3T; X-ray; 2.35 A; A/B=1-226.
DR   PDB; 1G3W; X-ray; 2.40 A; A=1-226.
DR   PDB; 1G3Y; X-ray; 2.80 A; A=1-226.
DR   PDB; 1P92; X-ray; 2.10 A; A=1-226.
DR   PDB; 1QVP; NMR; -; A=148-226.
DR   PDB; 1QW1; NMR; -; A=110-226.
DR   PDB; 1XCV; X-ray; 2.10 A; A=1-139.
DR   PDB; 2DTR; X-ray; 1.90 A; A=1-226.
DR   PDB; 2QQ9; X-ray; 1.71 A; A=1-226.
DR   PDB; 2QQA; X-ray; 2.10 A; A=1-226.
DR   PDB; 2QQB; X-ray; 1.92 A; A=1-226.
DR   PDB; 2TDX; X-ray; 2.40 A; A=1-226.
DR   PDB; 3GLX; X-ray; 1.85 A; A=1-226.
DR   PDBsum; 1BI0; -.
DR   PDBsum; 1BI1; -.
DR   PDBsum; 1BI2; -.
DR   PDBsum; 1BI3; -.
DR   PDBsum; 1BYM; -.
DR   PDBsum; 1C0W; -.
DR   PDBsum; 1DDN; -.
DR   PDBsum; 1DPR; -.
DR   PDBsum; 1F5T; -.
DR   PDBsum; 1FWZ; -.
DR   PDBsum; 1G3S; -.
DR   PDBsum; 1G3T; -.
DR   PDBsum; 1G3W; -.
DR   PDBsum; 1G3Y; -.
DR   PDBsum; 1P92; -.
DR   PDBsum; 1QVP; -.
DR   PDBsum; 1QW1; -.
DR   PDBsum; 1XCV; -.
DR   PDBsum; 2DTR; -.
DR   PDBsum; 2QQ9; -.
DR   PDBsum; 2QQA; -.
DR   PDBsum; 2QQB; -.
DR   PDBsum; 2TDX; -.
DR   PDBsum; 3GLX; -.
DR   DisProt; DP00374; -.
DR   ProteinModelPortal; P0DJL7; -.
DR   SMR; P0DJL7; 2-226.
DR   EnsemblBacteria; CAE49945; CAE49945; DIP1414.
DR   GeneID; 2649688; -.
DR   KEGG; cdi:DIP1414; -.
DR   eggNOG; COG1321; -.
DR   HOGENOM; HOG000096101; -.
DR   KO; K03709; -.
DR   OMA; HTIRIEE; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
DR   GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.10.10; -; 1.
DR   Gene3D; 1.10.60.10; -; 1.
DR   InterPro; IPR007167; Fe-transptr_FeoA.
DR   InterPro; IPR001367; Fe_dep_repressor.
DR   InterPro; IPR022689; Fe_dep_repressor_HTH_DtxR.
DR   InterPro; IPR022687; Fe_dep_repressor_HTH_DtxR_N.
DR   InterPro; IPR008988; Transcriptional_repressor_C.
DR   InterPro; IPR011991; WHTH_DNA-bd_dom.
DR   Pfam; PF02742; Fe_dep_repr_C; 1.
DR   Pfam; PF01325; Fe_dep_repress; 1.
DR   Pfam; PF04023; FeoA; 1.
DR   SMART; SM00899; FeoA; 1.
DR   SMART; SM00529; HTH_DTXR; 1.
DR   SUPFAM; SSF47979; SSF47979; 1.
DR   SUPFAM; SSF50037; SSF50037; 1.
DR   PROSITE; PS50944; HTH_DTXR; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Complete proteome; Cytoplasm; DNA-binding; Iron;
KW   Reference proteome; Repressor; Transcription;
KW   Transcription regulation.
FT   CHAIN         1    226       Diphtheria toxin repressor.
FT                                /FTId=PRO_0000201106.
FT   DOMAIN        4     65       HTH dtxR-type. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00296}.
FT   VARIANT      47     47       R -> H (in iron-insensitive tox
FT                                constitutive mutant C7hm723).
FT   VARIANT     141    141       G -> R (in strain: CD95/211-).
FT   VARIANT     147    147       V -> A (in strain: C7(-), C7hm723(-),
FT                                1030(-), CD95/305-, CD95/211- and CD95/
FT                                407-).
FT   VARIANT     165    165       I -> V (in strain: 1030(-)).
FT   VARIANT     174    174       V -> A (in strain: 1030(-)).
FT   VARIANT     191    191       S -> T (in strain: 1030(-)).
FT   VARIANT     199    199       D -> V (in strain: CD95/407-).
FT   VARIANT     201    201       H -> R (in strain: CD95/305-).
FT   VARIANT     205    205       S -> R (in strain: 1030(-)).
FT   VARIANT     214    214       I -> L (in strain: C7(-), C7hm723(-),
FT                                CD95/305-, CD95/211- and CD95/407-).
FT   VARIANT     214    214       I -> Y (in strain: 1030(-)).
FT   VARIANT     218    218       A -> T (in strain: 1030(-)).
FT   VARIANT     221    221       I -> M (in strain: CD95/211-).
FT   VARIANT     221    221       I -> T (in strain: CD95/407-).
FT   HELIX         4     21
FT   HELIX        27     34
FT   HELIX        38     50
FT   STRAND       53     56
FT   STRAND       60     64
FT   HELIX        66     88
FT   HELIX        94    104
FT   TURN        105    107
FT   HELIX       110    119
FT   STRAND      127    130
FT   HELIX       135    138
FT   STRAND      145    148
FT   STRAND      149    151
FT   HELIX       152    155
FT   STRAND      161    167
FT   HELIX       170    172
FT   HELIX       177    184
FT   STRAND      188    195
FT   STRAND      197    199
FT   STRAND      203    208
FT   STRAND      210    212
FT   HELIX       215    220
FT   STRAND      222    224
SQ   SEQUENCE   226 AA;  25344 MW;  A14F89FDB8719D5C CRC64;
     MKDLVDTTEM YLRTIYELEE EGVTPLRARI AERLEQSGPT VSQTVARMER DGLVVVASDR
     SLQMTPTGRT LATAVMRKHR LAERLLTDII GLDINKVHDE ACRWEHVMSD EVERRLVKVL
     KDVSRSPFGN PIPGLDELGV GNSDAAVPGT RVIDAATSMP RKVRIVQINE IFQVETDQFT
     QLLDADIRVG SEVEIVDRDG HITLSHNGKD VELIDDLAHT IRIEEL
//