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 24-JUL-2024, entry version 70. 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; Actinomycetota; Actinomycetes; Mycobacteriales; OC 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 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; DOI=10.1128/jb.174.4.1268-1272.1992; RA Boyd J.M., Hall K.C., Murphy J.R.; RT "DNA sequences and characterization of dtxR alleles from Corynebacterium RT 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 in the RT 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., Hamlin N., RA Holroyd S., Jagels K., Moule S., Quail M.A., Rabbinowitsch E., RA Rutherford K.M., Thomson N.R., Unwin L., Whitehead S., Barrell B.G., RA Parkhill J.; RT "The complete genome sequence and analysis of Corynebacterium diphtheriae RT 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 repressor."; RL Proc. Natl. Acad. Sci. U.S.A. 89:7576-7580(1992). RN [6] RP METAL-BINDING. RX PubMed=1400485; DOI=10.1016/s0021-9258(19)36677-3; 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 palindromic RT 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 with RT cobalt and manganese reveals an SH3-like third domain and suggests a RT 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 diphtheria RT 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; DOI=10.1128/iai.67.4.1806-1811.1999; 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., 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 binding CC and may associate with the tox operator. Binding of dtxR to tox CC operator requires a divalent metal ion such as cobalt, ferric, CC manganese, and nickel ions whereas zinc ions show weak 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 therefore CC represent a potential reservoir for toxygenic C.diphtheriae. CC -!- SIMILARITY: Belongs to the DtxR/MntR family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 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 AlphaFoldDB; P0DJL7; -. DR BMRB; P0DJL7; -. DR SMR; P0DJL7; -. DR STRING; 257309.DIP1414; -. DR KEGG; cdi:DIP1414; -. DR HOGENOM; CLU_069532_0_0_11; -. DR EvolutionaryTrace; P0DJL7; -. DR PHI-base; PHI:11204; -. DR Proteomes; UP000002198; Chromosome. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro. DR GO; GO:0042802; F:identical protein binding; IPI:CAFA. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0017124; F:SH3 domain binding; IMP:CAFA. DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IEA:TreeGrafter. DR Gene3D; 2.30.30.90; -; 1. DR Gene3D; 1.10.60.10; Iron dependent repressor, metal binding and dimerisation domain; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR InterPro; IPR050536; DtxR_MntR_Metal-Reg. DR InterPro; IPR040767; DtxR_SH3. DR InterPro; IPR007167; Fe-transptr_FeoA. DR InterPro; IPR001367; Fe_dep_repressor. DR InterPro; IPR036421; Fe_dep_repressor_sf. DR InterPro; IPR038157; FeoA_core_dom. DR InterPro; IPR022687; HTH_DTXR. DR InterPro; IPR022689; Iron_dep_repressor. DR InterPro; IPR008988; Transcriptional_repressor_C. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR PANTHER; PTHR33238; IRON (METAL) DEPENDENT REPRESSOR, DTXR FAMILY; 1. DR PANTHER; PTHR33238:SF10; IRON-DEPENDENT REPRESSOR IDER; 1. DR Pfam; PF18357; DtxR; 1. DR Pfam; PF02742; Fe_dep_repr_C; 1. DR Pfam; PF01325; Fe_dep_repress; 1. DR SMART; SM00899; FeoA; 1. DR SMART; SM00529; HTH_DTXR; 1. DR SUPFAM; SSF50037; C-terminal domain of transcriptional repressors; 1. DR SUPFAM; SSF47979; Iron-dependent repressor protein, dimerization domain; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS50944; HTH_DTXR; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; DNA-binding; Iron; Reference proteome; Repressor; KW Transcription; Transcription regulation. FT CHAIN 1..226 FT /note="Diphtheria toxin repressor" FT /id="PRO_0000201106" FT DOMAIN 4..65 FT /note="HTH dtxR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00296" FT VARIANT 47 FT /note="R -> H (in iron-insensitive tox constitutive mutant FT C7hm723)" FT VARIANT 141 FT /note="G -> R (in strain: CD95/211-)" FT VARIANT 147 FT /note="V -> A (in strain: C7(-), C7hm723(-), 1030(-), CD95/ FT 305-, CD95/211- and CD95/407-)" FT VARIANT 165 FT /note="I -> V (in strain: 1030(-))" FT VARIANT 174 FT /note="V -> A (in strain: 1030(-))" FT VARIANT 191 FT /note="S -> T (in strain: 1030(-))" FT VARIANT 199 FT /note="D -> V (in strain: CD95/407-)" FT VARIANT 201 FT /note="H -> R (in strain: CD95/305-)" FT VARIANT 205 FT /note="S -> R (in strain: 1030(-))" FT VARIANT 214 FT /note="I -> L (in strain: C7(-), C7hm723(-), CD95/305-, FT CD95/211- and CD95/407-)" FT VARIANT 214 FT /note="I -> Y (in strain: 1030(-))" FT VARIANT 218 FT /note="A -> T (in strain: 1030(-))" FT VARIANT 221 FT /note="I -> M (in strain: CD95/211-)" FT VARIANT 221 FT /note="I -> T (in strain: CD95/407-)" FT HELIX 4..21 FT /evidence="ECO:0007829|PDB:2QQ9" FT HELIX 27..34 FT /evidence="ECO:0007829|PDB:2QQ9" FT HELIX 38..50 FT /evidence="ECO:0007829|PDB:2QQ9" FT STRAND 53..56 FT /evidence="ECO:0007829|PDB:2QQ9" FT STRAND 60..64 FT /evidence="ECO:0007829|PDB:2QQ9" FT HELIX 66..88 FT /evidence="ECO:0007829|PDB:2QQ9" FT HELIX 94..104 FT /evidence="ECO:0007829|PDB:2QQ9" FT TURN 105..107 FT /evidence="ECO:0007829|PDB:2QQ9" FT HELIX 110..119 FT /evidence="ECO:0007829|PDB:2QQ9" FT STRAND 127..130 FT /evidence="ECO:0007829|PDB:1DPR" FT HELIX 135..138 FT /evidence="ECO:0007829|PDB:2QQ9" FT STRAND 145..148 FT /evidence="ECO:0007829|PDB:1QW1" FT STRAND 149..151 FT /evidence="ECO:0007829|PDB:2QQA" FT HELIX 152..155 FT /evidence="ECO:0007829|PDB:2QQ9" FT STRAND 161..167 FT /evidence="ECO:0007829|PDB:2QQ9" FT HELIX 170..172 FT /evidence="ECO:0007829|PDB:2QQ9" FT HELIX 177..184 FT /evidence="ECO:0007829|PDB:2QQ9" FT STRAND 188..195 FT /evidence="ECO:0007829|PDB:2QQ9" FT STRAND 197..199 FT /evidence="ECO:0007829|PDB:1P92" FT STRAND 203..208 FT /evidence="ECO:0007829|PDB:2QQ9" FT STRAND 210..212 FT /evidence="ECO:0007829|PDB:2QQ9" FT HELIX 215..220 FT /evidence="ECO:0007829|PDB:2QQ9" FT STRAND 222..224 FT /evidence="ECO:0007829|PDB:2QQ9" 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 //