P0DJL7 (DTXR_CORDI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Diphtheria toxin repressor

Alternative name(s):
Iron-dependent diphtheria tox regulatory element
Tox regulatory factor

Gene names

Name:	dtxR
Ordered Locus Names:	DIP1414

Organism

Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis) [Complete proteome] [HAMAP]

Taxonomic identifier

257309 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Actinobacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Corynebacteriaceae › Corynebacterium › Corynebacterium diphtheriae

Protein attributes

Sequence length	226 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Iron-binding repressor of the dipheteria toxin gene expression. May serve as a global regulator of gene expression. Represses ripA under iron excess. Ref.3
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Miscellaneous	The N-terminal region may be involved in iron binding and may associate with the tox operator. Binding of dtxR to tox operator requires a divalent metal ion such as cobalt, ferric, manganese, and nickel ions whereas zinc ions show weak activation. The dtxR gene was functional in the non-toxygenic strains CD95/211-, CD95/305- and CD95/407- isolated in the United Kingdom. These findings demonstrate that, if lysogenised by a bacteriophage, non-toxygenic strains could produce toxin and therefore represent a potential reservoir for toxygenic C.diphtheriae.
Sequence similarities	Contains 1 HTH dtxR-type DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm
Ligand	DNA-binding Iron
Molecular function	Repressor
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological_process	transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro transition metal ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 226

226

Diphtheria toxin repressor

PRO_0000201106

Regions

Domain

4 – 65

62

HTH dtxR-type

Natural variations

Natural variant

47

1

R → H in iron-insensitive tox constitutive mutant C7hm723.

Natural variant

141

1

G → R in strain: CD95/211-.

Natural variant

147

1

V → A in strain: C7(-), C7hm723(-), 1030(-), CD95/305-, CD95/211- and CD95/407-.

Natural variant

165

1

I → V in strain: 1030(-).

Natural variant

174

1

V → A in strain: 1030(-).

Natural variant

191

1

S → T in strain: 1030(-).

Natural variant

199

1

D → V in strain: CD95/407-.

Natural variant

201

1

H → R in strain: CD95/305-.

Natural variant

205

1

S → R in strain: 1030(-).

Natural variant

214

1

I → L in strain: C7(-), C7hm723(-), CD95/305-, CD95/211- and CD95/407-.

Natural variant

214

1

I → Y in strain: 1030(-).

Natural variant

218

1

A → T in strain: 1030(-).

Natural variant

221

1

I → M in strain: CD95/211-.

Natural variant

221

1

I → T in strain: CD95/407-.

Secondary structure

1

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226

Helix Strand Turn

Details...

Helix

4 – 21

18

Helix

27 – 34

8

Helix

38 – 50

13

Beta strand

53 – 56

4

Beta strand

60 – 64

5

Helix

66 – 88

23

Helix

94 – 104

11

Turn

105 – 107

3

Helix

110 – 119

10

Helix

135 – 138

4

Beta strand

145 – 148

4

Beta strand

149 – 151

3

Helix

152 – 155

4

Beta strand

161 – 167

7

Helix

170 – 172

3

Helix

177 – 184

8

Beta strand

188 – 195

8

Beta strand

203 – 208

6

Beta strand

210 – 212

3

Helix

215 – 220

6

Beta strand

222 – 224

3

Sequences

	Sequence		Length	Mass (Da)
	P0DJL7 [UniParc]. Last modified September 5, 2012. Version 1. Checksum: A14F89FDB8719D5C	FASTA	226	25,344
	10 20 30 40 50 60 MKDLVDTTEM YLRTIYELEE EGVTPLRARI AERLEQSGPT VSQTVARMER DGLVVVASDR 70 80 90 100 110 120 SLQMTPTGRT LATAVMRKHR LAERLLTDII GLDINKVHDE ACRWEHVMSD EVERRLVKVL 130 140 150 160 170 180 KDVSRSPFGN PIPGLDELGV GNSDAAVPGT RVIDAATSMP RKVRIVQINE IFQVETDQFT 190 200 210 220 QLLDADIRVG SEVEIVDRDG HITLSHNGKD VELIDDLAHT IRIEEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and DNA sequence analysis of a diphtheria tox iron-dependent regulatory element (dtxR) from Corynebacterium diphtheriae." Boyd J.M., Oza M.N., Murphy J.R. Proc. Natl. Acad. Sci. U.S.A. 87:5968-5972(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: C7(-).
[2]	"DNA sequences and characterization of dtxR alleles from Corynebacterium diphtheriae PW8(-), 1030(-), and C7hm723(-)." Boyd J.M., Hall K.C., Murphy J.R. J. Bacteriol. 174:1268-1272(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 1030(-) and C7hm723(-).
[3]	"Molecular characterization of diphtheria toxin repressor (dtxR) genes present in nontoxigenic Corynebacterium diphtheriae strains isolated in the United Kingdom." De Zoysa A.S., Efstratiou A., Hawkey P.M. J. Clin. Microbiol. 43:223-228(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], STUDY OF FUNCTIONALITY. Strain: CD95/211-, CD95/305- and CD95/407-.
[4]	"The complete genome sequence and analysis of Corynebacterium diphtheriae NCTC13129." Cerdeno-Tarraga A.-M., Efstratiou A., Dover L.G., Holden M.T.G., Pallen M.J., Bentley S.D., Besra G.S., Churcher C.M., James K.D., De Zoysa A., Chillingworth T., Cronin A., Dowd L., Feltwell T., Hamlin N., Holroyd S., Jagels K., Moule S. , Quail M.A., Rabbinowitsch E., Rutherford K.M., Thomson N.R., Unwin L., Whitehead S., Barrell B.G., Parkhill J. Nucleic Acids Res. 31:6516-6523(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 700971 / NCTC 13129 / Biotype gravis.
[5]	"Purification and characterization of the diphtheria toxin repressor." Schmitt M.P., Twiddy E.M., Holmes R.K. Proc. Natl. Acad. Sci. U.S.A. 89:7576-7580(1992) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[6]	"Binding of the metalloregulatory protein DtxR to the diphtheria tox operator requires a divalent heavy metal ion and protects the palindromic sequence from DNase I digestion." Tao X., Murphy J.R. J. Biol. Chem. 267:21761-21764(1992) [PubMed] [Europe PMC] [Abstract] Cited for: METAL-BINDING.
[7]	"High-resolution structure of the diphtheria toxin repressor complexed with cobalt and manganese reveals an SH3-like third domain and suggests a possible role of phosphate as co-corepressor." Qiu X., Pohl E., Holmes R.K., Hol W.G.J. Biochemistry 35:12292-12302(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[8]	"Structures of the apo- and the metal ion-activated forms of the diphtheria tox repressor from Corynebacterium diphtheriae." Schiering N., Tao X., Zeng H., Murphy J.R., Petsko G.A., Ringe D. Proc. Natl. Acad. Sci. U.S.A. 92:9843-9850(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[9]	"Structure of the metal-ion-activated diphtheria toxin repressor/tox operator complex." White A., Ding X., Vanderspek J.C., Murphy J.R., Ringe D. Nature 394:502-506(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[10]	"Anion-coordinating residues at binding site 1 are essential for the biological activity of the diphtheria toxin repressor." Goranson-Siekierke J., Pohl E., Hol W.G.J., Holmes R.K. Infect. Immun. 67:1806-1811(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[11]	"Solution structure and peptide binding studies of the C-terminal src homology 3-like domain of the diphtheria toxin repressor protein." Wang G., Wylie G.P., Twigg P.D., Caspar D.L.D., Murphy J.R., Logan T.M. Proc. Natl. Acad. Sci. U.S.A. 96:6119-6124(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 130-226.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M34239 Genomic DNA. Translation: AAA23296.1.
M80336 Genomic DNA. Translation: AAA23302.1.
M80337 Genomic DNA. Translation: AAA23301.1.
AY741368 Genomic DNA. Translation: AAU93781.1.
AY741369 Genomic DNA. Translation: AAU93782.1.
AY741370 Genomic DNA. Translation: AAU93783.1.
BX248358 Genomic DNA. Translation: CAE49945.1.

PIR

A35968.

RefSeq

NP_939766.1. NC_002935.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BI0	X-ray	2.30	A	1-226	[»]
1BI1	X-ray	2.20	A	1-226	[»]
1BI2	X-ray	2.30	A/B	1-226	[»]
1BI3	X-ray	2.40	A/B	1-226	[»]
1BYM	NMR	-	A	130-226	[»]
1C0W	X-ray	3.20	A/B/C/D	2-226	[»]
1DDN	X-ray	3.00	A/B/C/D	1-226	[»]
1DPR	X-ray	3.00	A/B	1-226	[»]
1F5T	X-ray	3.00	A/B/C/D	1-121	[»]
1FWZ	X-ray	2.30	A	1-226	[»]
1G3S	X-ray	2.40	A	1-226	[»]
1G3T	X-ray	2.35	A/B	1-226	[»]
1G3W	X-ray	2.40	A	1-226	[»]
1G3Y	X-ray	2.80	A	1-226	[»]
1P92	X-ray	2.10	A	1-226	[»]
1QVP	NMR	-	A	144-226	[»]
1QW1	NMR	-	A	110-226	[»]
1XCV	X-ray	2.10	A	1-139	[»]
2DTR	X-ray	1.90	A	1-226	[»]
2QQ9	X-ray	1.71	A	1-226	[»]
2QQA	X-ray	2.10	A	1-226	[»]
2QQB	X-ray	1.92	A	1-226	[»]
2TDX	X-ray	2.40	A	1-226	[»]
3GLX	X-ray	1.85	A	1-226	[»]

DisProt

DP00374.

ProteinModelPortal

P0DJL7.

SMR

P0DJL7. Positions 2-226.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

CAE49945; CAE49945; DIP1414.

GeneID

2649688.

KEGG

cdi:DIP1414.

Organism-specific databases

CMR

Search...

Phylogenomic databases

eggNOG

COG1321.

HOGENOM

HOG000096101.

KO

K03709.

OMA

VDIINEQ.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.
1.10.60.10. 1 hit.

InterPro

IPR007167. Fe-transptr_FeoA.
IPR001367. Fe_dep_repressor.
IPR022689. Fe_dep_repressor_HTH_DtxR.
IPR022687. Fe_dep_repressor_HTH_DtxR_N.
IPR008988. Transcriptional_repressor_C.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF02742. Fe_dep_repr_C. 1 hit.
PF01325. Fe_dep_repress. 1 hit.
PF04023. FeoA. 1 hit.
[Graphical view]

SMART

SM00899. FeoA. 1 hit.
SM00529. HTH_DTXR. 1 hit.
[Graphical view]

SUPFAM

SSF47979. HTH_DtxR. 1 hit.
SSF50037. Transcr_rep_C. 1 hit.

PROSITE

PS50944. HTH_DTXR. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

DTXR_CORDI

Accession

Primary (citable) accession number: P0DJL7
Secondary accession number(s): P33120 , Q5XQ41, Q5XQ42, Q5XQ43

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2012
Last sequence update:	September 5, 2012
Last modified:	May 1, 2013
This is version 8 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program