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142  structures 4277  species 0  interactions 6983  sequences 30  architectures

Family: Fe_dep_repr_C (PF02742)

Summary: Iron dependent repressor, metal binding and dimerisation domain

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This is the Wikipedia entry entitled "Iron dependent repressor". More...

Iron dependent repressor Edit Wikipedia article

Iron dependent repressor, N-terminal DNA binding domain (dtxR-type HTH domain)
PDB 1u8r EBI.jpg
crystal structure of an ider-dna complex reveals a conformational change in activated ider for base-specific interactions
Pfam clanCL0123
Iron dependent repressor, metal binding and dimerisation domain
PDB 2hyf EBI.jpg
the structure of apo-mntr from bacillus subtilis, selenomethionine derivative
Pfam clanCL0123

In molecular biology, the iron dependent repressors are a family of bacterial and archaeal transcriptional repressors.

At their N-terminus they contain a dtxR-type HTH domain. This is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 65 amino acids present in metalloregulators of the dtxR/mntR family. The domain is named after Corynebacterium diphtheriae dtxR, an iron-specific diphtheria toxin repressor, and Bacillus subtilis mntR, a manganese transport regulator. Iron-responsive metalloregulators such as dtxR and ideR occur in Gram-positive bacteria of the high GC branch, while manganese-responsive metalloregulators like mntR are described in diverse genera of Gram-positive and Gram-negative bacteria and also in Archaea.[1] The metalloregulators like dtxR/mntR contain the DNA-binding dtxR-type HTHdomain usually in the N-terminal part. The C-terminal part contains a dimerisation domain with two metal-binding sites, although the primary metal-binding site is less conserved in the Mn(II)-regulators. Fe(II)-regulated proteins contain an SH3-like domain as a C-terminal extension, which is absent in Mn(II)-regulated mntR.[2][3]

Metal-ion dependent regulators orchestrate the virulence of several important human pathogens. The dtxR protein regulates the expression of diphtheria toxin in response to environmental iron concentrations. Furthermore, dtxR and ideR control iron uptake.[4] Homeostasis of manganese, which is an essential nutrient, is regulated by mntR. A typical dtxR-type metalloregulator binds two divalent metal effectors per monomer, upon which allosteric changes occur that moderate binding to the cognate DNA operators. Iron-bound dtxR homodimers bind to an interrupted palindrome of 19 bp, protecting a sequence of ~30 bp. The crystal structures of iron-regulated and manganese-regulated repressors show that the DNA binding domain contains three alpha-helices and a pair of antiparallel beta-strands. Helices 2 and 3 comprise the helix-turn-helix motif and the beta-strands are called the wing.[3] This wHTH topology is similar to the lysR-type HTH. Most dtxR-type metalloregulators bind as dimers to the DNA major groove.

Several proteins are known to contain a dtxR-type HTH domain. These include: Corynebacterium diphtheriae dtxR, a diphtheria toxin repressor,[5] which regulates the expression of the high-affinity iron uptake system, other iron-sensitive genes, and the bacteriophage tox gene. Metal-bound dtxR represses transcription by binding the tox operator; if iron is limiting, conformational changes of the wHTH disrupt DNA-binding and the diphtheria toxin is produced. Mycobacterium tuberculosis ideR, an iron-dependent regulator that is essential for this pathogen. The regulator represses genes for iron acquisition and activates iron storage genes, and is a positive regulator of oxidative stress responses.[4] Bacillus subtilis mntR, a manganese transport regulator, binds Mn2+ as an effector and is a transcriptional repressor of transporters for the import of manganese. Treponema pallidum troR, a metal-dependent transcriptional repressor. Archaeoglobus fulgidus MDR1 (troR), a metal-dependent transcriptional repressor, which negatively regulates its own transcription.


  1. ^ Guedon E, Helmann JD (April 2003). "Origins of metal ion selectivity in the DtxR/MntR family of metalloregulators". Mol. Microbiol. 48 (2): 495–506. doi:10.1046/j.1365-2958.2003.03445.x. PMID 12675807.
  2. ^ Spiering MM, Ringe D, Murphy JR, Marletta MA (April 2003). "Metal stoichiometry and functional studies of the diphtheria toxin repressor". Proc. Natl. Acad. Sci. U.S.A. 100 (7): 3808–13. doi:10.1073/pnas.0737977100. PMC 153003. PMID 12655054.
  3. ^ a b Glasfeld A, Guedon E, Helmann JD, Brennan RG (August 2003). "Structure of the manganese-bound manganese transport regulator of Bacillus subtilis". Nat. Struct. Biol. 10 (8): 652–7. doi:10.1038/nsb951. PMID 12847518. S2CID 23359112.
  4. ^ a b Rodriguez GM, Smith I (March 2003). "Mechanisms of iron regulation in mycobacteria: role in physiology and virulence". Mol. Microbiol. 47 (6): 1485–94. doi:10.1046/j.1365-2958.2003.03384.x. PMID 12622807.
  5. ^ Schiering N, Tao X, Zeng H, Murphy JR, Petsko GA, Ringe D (October 1995). "Structures of the apo- and the metal ion-activated forms of the diphtheria tox repressor from Corynebacterium diphtheriae". Proc. Natl. Acad. Sci. U.S.A. 92 (21): 9843–50. doi:10.1073/pnas.92.21.9843. PMC 40899. PMID 7568230.
This article incorporates text from the public domain Pfam and InterPro: IPR022687

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Iron dependent repressor, metal binding and dimerisation domain Provide feedback

This family includes the Diphtheria toxin repressor [1]. It acts as an iron-binding repressor of diphtheria toxin gene expression and may serve as a global regulator of gene expression. DTXR comprises an N-terminal DNA-binding domain, an interface domain (which contains two metal-binding sites) and a third, very flexible C-terminal domain. The second domain is responsible for dimerization and metal binding. Binding of DTXR to Tox operator requires a divalent metal ion such as cobalt, ferric, manganese and nickel whereas zinc shows weak activation [2]. This domain can also bind Cd(II), Ca(II) and Cu(II) (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1.

Literature references

  1. Schiering N, Tao X, Zeng H, Murphy JR, Petsko GA, Ringe D; , Proc Natl Acad Sci USA 1995;92:9843-9850.: Structures of the apo- and the metal ion-activated forms of the diphtheria tox repressor from Corynebacterium diphtheriae. PUBMED:7568230 EPMC:7568230

  2. Qiu X, Verlinde CL, Zhang S, Schmitt MP, Holmes RK, Hol WG; , Structure 1995;3:87-100.: Three-dimensional structure of the diphtheria toxin repressor in complex with divalent cation co-repressors. PUBMED:7743135 EPMC:7743135

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001367

The diphtheria toxin repressor protein (DTXR) is a member of this group [ PUBMED:7568230 ]. In Corynebacterium diphtheriae where it has been studied in some detail this protein acts as an iron-binding repressor of dipheteria toxin gene expression and may serve as a global regulator of gene expression. DTXR comprises an N-terminal DNA-binding domain, an interface domain (which contains two metal-binding sites) and a third, very flexible C-terminal domain. The second domain is responsible for dimerization and metal binding. The N terminus 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 whereas zinc shows weak activation [ PUBMED:7743135 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan HTH (CL0123), which has the following description:

This family contains a diverse range of mostly DNA-binding domains that contain a helix-turn-helix motif.

The clan contains the following 381 members:

AbiEi_3_N AbiEi_4 ANAPC2 AphA_like AraR_C Arg_repressor ARID ArsR B-block_TFIIIC B5 Bac_DnaA_C Baculo_PEP_N BetR BHD_3 BLACT_WH Bot1p BrkDBD BrxA BsuBI_PstI_RE_N C_LFY_FLO CaiF_GrlA CarD_CdnL_TRCF CDC27 Cdc6_C Cdh1_DBD_1 CDT1 CDT1_C CENP-B_N Costars CPSase_L_D3 Cro Crp CSN4_RPN5_eIF3a CSN8_PSD8_EIF3K CtsR Cullin_Nedd8 CUT CUTL CvfB_WH DBD_HTH DDRGK DEP Dimerisation Dimerisation2 DNA_binding_1 DNA_meth_N DpnI_C DprA_WH DsrC DsrD DUF1016_N DUF1133 DUF1153 DUF1323 DUF134 DUF1376 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2513 DUF2551 DUF2582 DUF3116 DUF3161 DUF3253 DUF3489 DUF3853 DUF3860 DUF3895 DUF3908 DUF433 DUF434 DUF4364 DUF4373 DUF4423 DUF4447 DUF4777 DUF480 DUF4817 DUF5635 DUF573 DUF5805 DUF6088 DUF6262 DUF6362 DUF6432 DUF6462 DUF6471 DUF722 DUF739 DUF742 DUF937 DUF977 E2F_TDP EAP30 eIF-5_eIF-2B ELL ESCRT-II Ets EutK_C Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC FokI_D1 FokI_dom_2 Forkhead FtsK_gamma FUR GcrA GerE GntR GP3_package HARE-HTH HemN_C HNF-1_N Homeobox_KN Homeodomain Homez HPD HrcA_DNA-bdg HSF_DNA-bind HTH_1 HTH_10 HTH_11 HTH_12 HTH_13 HTH_15 HTH_16 HTH_17 HTH_18 HTH_19 HTH_20 HTH_21 HTH_22 HTH_23 HTH_24 HTH_25 HTH_26 HTH_27 HTH_28 HTH_29 HTH_3 HTH_30 HTH_31 HTH_32 HTH_33 HTH_34 HTH_35 HTH_36 HTH_37 HTH_38 HTH_39 HTH_40 HTH_41 HTH_42 HTH_43 HTH_45 HTH_46 HTH_47 HTH_48 HTH_49 HTH_5 HTH_50 HTH_51 HTH_52 HTH_53 HTH_54 HTH_55 HTH_56 HTH_57 HTH_58 HTH_59 HTH_6 HTH_60 HTH_61 HTH_7 HTH_8 HTH_9 HTH_ABP1_N HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_micro HTH_OrfB_IS605 HTH_PafC HTH_ParB HTH_psq HTH_SUN2 HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_2 HTH_Tnp_4 HTH_Tnp_IS1 HTH_Tnp_IS630 HTH_Tnp_ISL3 HTH_Tnp_Mu_1 HTH_Tnp_Mu_2 HTH_Tnp_Tc3_1 HTH_Tnp_Tc3_2 HTH_Tnp_Tc5 HTH_WhiA HxlR IBD IF2_N IRF KicB KilA-N Kin17_mid KORA KorB La LacI LexA_DNA_bind Linker_histone LZ_Tnp_IS481 MADF_DNA_bdg MAGE MARF1_LOTUS MarR MarR_2 MC6 MC7 MC8 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 MogR_DNAbind Mor MotA_activ MqsA_antitoxin MRP-L20 Mrr_N MukE Myb_DNA-bind_2 Myb_DNA-bind_3 Myb_DNA-bind_4 Myb_DNA-bind_5 Myb_DNA-bind_6 Myb_DNA-bind_7 Myb_DNA-binding Neugrin NFRKB_winged NOD2_WH NUMOD1 ORC_WH_C OST-HTH P22_Cro PaaX PadR PapB PAX PCI Penicillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_NinH Phage_Nu1 Phage_rep_O Phage_rep_org_N Phage_terminase PheRS_DBD1 PheRS_DBD2 PheRS_DBD3 PhetRS_B1 Pou Pox_D5 PqqD PRC2_HTH_1 PUFD PuR_N Put_DNA-bind_N pXO2-72 Raf1_HTH Rap1-DNA-bind Rep_3 RepA_C RepA_N RepB RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S18 Ribosomal_S19e Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RNA_pol_Rpc82 RNase_H2-Ydr279 ROQ_II ROXA-like_wH RP-C RPA RPA_C RPN6_C_helix RQC Rrf2 RTP RuvB_C S10_plectin SAC3_GANP SANT_DAMP1_like SatD SelB-wing_1 SelB-wing_2 SelB-wing_3 SgrR_N Sigma54_CBD Sigma54_DBD Sigma70_ECF Sigma70_ner Sigma70_r2 Sigma70_r3 Sigma70_r4 Sigma70_r4_2 SinI SKA1 Ski_Sno SLIDE Slx4 SMC_Nse1 SMC_ScpB SoPB_HTH SpoIIID SRP19 SRP_SPB STN1_2 Stn1_C Stork_head Sulfolobus_pRN Suv3_N Swi6_N SWIRM Tau95 TBPIP TEA Terminase_5 TetR_N TFA2_Winged_2 TFIIE_alpha TFIIE_beta TFIIF_alpha TFIIF_beta Tn7_Tnp_TnsA_C Tn916-Xis TraI_2_C Trans_reg_C TrfA TrmB tRNA_bind_2 tRNA_bind_3 Trp_repressor UPF0122 UPF0175 Vir_act_alpha_C XPA_C Xre-like-HTH YdaS_antitoxin YidB YjcQ YokU z-alpha


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Curation and family details

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Curation View help on the curation process

Seed source: Sarah Teichmann
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Griffiths-Jones SR
Number in seed: 379
Number in full: 6983
Average length of the domain: 67.00 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 33.30 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 27.0 27.0
Noise cut-off 26.8 26.9
Model length: 70
Family (HMM) version: 18
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Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Fe_dep_repr_C domain has been found. There are 142 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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