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70  structures 6778  species 0  interactions 18551  sequences 28  architectures

Family: FUR (PF01475)

Summary: Ferric uptake regulator family

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This is the Wikipedia entry entitled "Ferric uptake regulator family". More...

Ferric uptake regulator family Edit Wikipedia article

PDB 1mzb EBI.jpg
ferric uptake regulator
Pfam clanCL0123
Ferric uptake regulatory protein
OrganismEscherichia coli

In molecular biology, the ferric uptake regulator family is a family of bacterial proteins involved in regulating metal ion uptake and in metal homeostasis. The family is named for its founding member, known as the ferric uptake regulator or ferric uptake regulatory protein (Fur). Fur proteins are responsible for controlling the intracellular concentration of iron in many bacteria. Iron is essential for most organisms, but its concentration must be carefully managed over a wide range of environmental conditions; high concentrations can be toxic due to the formation of reactive oxygen species.[1]


Members of the ferric uptake regulator family are transcription factors that primarily exert their regulatory effects as repressors: when bound to their cognate metal ion, they are capable of binding DNA and preventing expression of the genes they regulate, but under low concentrations of metal, they undergo a conformational change that prevents DNA binding and lifts the repression.[2][3] In the case of the ferric uptake regulator protein itself, its immediate downstream target is a noncoding RNA called RyhB.[2]

In addition to the ferric uptake regulator protein, members of the Fur family are also involved in maintaining homeostasis with respect to other ions:[4]

The iron dependent repressor family is a functionally similar but non-homologous family of proteins involved in iron homeostasis in prokaryotes.[1]

Relationship to virulence

Metal homeostasis can be a factor in bacterial virulence, an observation with a particularly long history in the case of iron.[15][16][17] In some cases, expression of virulence factors is under the regulatory control of the Fur protein.[1][2]


  1. ^ a b c Pohl E, Haller JC, Mijovilovich A, Meyer-Klaucke W, Garman E, Vasil ML (February 2003). "Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator". Molecular Microbiology. 47 (4): 903–15. doi:10.1046/j.1365-2958.2003.03337.x. PMID 12581348.
  2. ^ a b c Porcheron G, Dozois CM (August 2015). "Interplay between iron homeostasis and virulence: Fur and RyhB as major regulators of bacterial pathogenicity" (PDF). Veterinary Microbiology. 179 (1–2): 2–14. doi:10.1016/j.vetmic.2015.03.024. PMID 25888312.
  3. ^ Gilston BA, Wang S, Marcus MD, Canalizo-Hernández MA, Swindell EP, Xue Y, Mondragón A, O'Halloran TV (November 2014). "Structural and mechanistic basis of zinc regulation across the E. coli Zur regulon". PLoS Biology. 12 (11): e1001987. doi:10.1371/journal.pbio.1001987. PMC 4219657. PMID 25369000.
  4. ^ Waldron KJ, Robinson NJ (January 2009). "How do bacterial cells ensure that metalloproteins get the correct metal?". Nature Reviews. Microbiology. 7 (1): 25–35. doi:10.1038/nrmicro2057. PMID 19079350.
  5. ^ Díaz-Mireles E, Wexler M, Sawers G, Bellini D, Todd JD, Johnston AW (May 2004). "The Fur-like protein Mur of Rhizobium leguminosarum is a Mn(2+)-responsive transcriptional regulator". Microbiology. 150 (Pt 5): 1447–56. doi:10.1099/mic.0.26961-0. PMID 15133106.
  6. ^ Platero R, Peixoto L, O'Brian MR, Fabiano E (July 2004). "Fur is involved in manganese-dependent regulation of mntA (sitA) expression in Sinorhizobium meliloti". Applied and Environmental Microbiology. 70 (7): 4349–55. doi:10.1128/AEM.70.7.4349-4355.2004. PMC 444773. PMID 15240318.
  7. ^ Chao TC, Becker A, Buhrmester J, Pühler A, Weidner S (June 2004). "The Sinorhizobium meliloti fur gene regulates, with dependence on Mn(II), transcription of the sitABCD operon, encoding a metal-type transporter". Journal of Bacteriology. 186 (11): 3609–20. doi:10.1128/JB.186.11.3609-3620.2004. PMC 415740. PMID 15150249.
  8. ^ Hohle TH, O'Brian MR (April 2009). "The mntH gene encodes the major Mn(2+) transporter in Bradyrhizobium japonicum and is regulated by manganese via the Fur protein". Molecular Microbiology. 72 (2): 399–409. doi:10.1111/j.1365-2958.2009.06650.x. PMC 2675660. PMID 19298371.
  9. ^ Menscher EA, Caswell CC, Anderson ES, Roop RM (February 2012). "Mur regulates the gene encoding the manganese transporter MntH in Brucella abortus 2308". Journal of Bacteriology. 194 (3): 561–6. doi:10.1128/JB.05296-11. PMC 3264066. PMID 22101848.
  10. ^ Ahn BE, Cha J, Lee EJ, Han AR, Thompson CJ, Roe JH (March 2006). "Nur, a nickel-responsive regulator of the Fur family, regulates superoxide dismutases and nickel transport in Streptomyces coelicolor". Molecular Microbiology. 59 (6): 1848–58. doi:10.1111/j.1365-2958.2006.05065.x. PMID 16553888.
  11. ^ Lee JW, Helmann JD (March 2006). "The PerR transcription factor senses H2O2 by metal-catalysed histidine oxidation". Nature. 440 (7082): 363–7. doi:10.1038/nature04537. PMID 16541078.
  12. ^ Graham AI, Hunt S, Stokes SL, Bramall N, Bunch J, Cox AG, McLeod CW, Poole RK (July 2009). "Severe zinc depletion of Escherichia coli: roles for high affinity zinc binding by ZinT, zinc transport and zinc-independent proteins". The Journal of Biological Chemistry. 284 (27): 18377–89. doi:10.1074/jbc.M109.001503. PMC 2709383. PMID 19377097.
  13. ^ Blindauer CA (March 2015). "Advances in the molecular understanding of biological zinc transport" (PDF). Chemical Communications. 51 (22): 4544–63. doi:10.1039/c4cc10174j. PMID 25627157.
  14. ^ O'Brian MR (2015). "Perception and Homeostatic Control of Iron in the Rhizobia and Related Bacteria". Annual Review of Microbiology. 69: 229–45. doi:10.1146/annurev-micro-091014-104432. PMID 26195304.
  15. ^ Bullen JJ, Rogers HJ, Griffiths E (1978). "Role of iron in bacterial infection". Current Topics in Microbiology and Immunology. 80: 1–35. PMID 352628.
  16. ^ Ratledge C, Dover LG (2000). "Iron metabolism in pathogenic bacteria". Annual Review of Microbiology. 54: 881–941. doi:10.1146/annurev.micro.54.1.881. PMID 11018148.
  17. ^ Litwin CM, Calderwood SB (April 1993). "Role of iron in regulation of virulence genes". Clinical Microbiology Reviews. 6 (2): 137–49. doi:10.1128/cmr.6.2.137. PMC 358274. PMID 8472246.
This article incorporates text from the public domain Pfam and InterPro: IPR002481

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Ferric uptake regulator family Provide feedback

This family includes metal ion uptake regulator proteins, that bind to the operator DNA and controls transcription of metal ion-responsive genes. This family is also known as the FUR family.

Literature references

  1. Escolar L, Perez-Martin J, de Lorenzo V; , J Mol Biol 1998;283:537-547.: Binding of the fur (ferric uptake regulator) repressor of Escherichia coli to arrays of the GATAAT sequence. PUBMED:9784364 EPMC:9784364

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002481

The Ferric uptake regulator (Fur) family includes metal ion uptake regulator proteins, which are responsible for controlling the intracellular concentration of iron in many bacteria. The Fur protein (a dimer having one Fe 2+ coordinated per monomer) acts as an iron-responsive, DNA-binding repressor protein that binds to a 'Furbox' with the consensus sequence GATAATGATAATCATTATC in the promoter of iron-regulated genes. Under low-iron condition, the Fur protein is released from the promoter and transcription resumed [ PUBMED:8522528 ]. Some members sense metal ions other than Fe 2+ . For example, the zinc uptake regulator (Zur) responds to Zn 2+ [ PUBMED:9680209 ], the manganese uptake regulator (Mur) responds to Mn 2+ , and the nickel uptake regulator (Nur) responds to Ni 2+ [ PUBMED:18259067 , PUBMED:16553888 ]. Other members sense signals other than metal ions. For example, PerR, a metal-dependent sensor of hydrogen peroxide. PerR regulates DNA-binding activity through metal-based protein oxidation, and co-ordinates Mn 2+ or Fe 2+ at its regulatory site [ PUBMED:16925555 ]. Furs can also control zinc homeostasis and is the subject of research on the pathogenesis of mycobacteria [ PUBMED:18452427 , PUBMED:12581348 ]. Fur family proteins contain an N-terminal winged-helix DNA-binding domain followed by a dimerization domain; this entry spans both those domains [ PUBMED:16774589 , PUBMED:17216355 , PUBMED:18945213 , PUBMED:12581348 , PUBMED:11466300 , PUBMED:9765558 , PUBMED:7590316 , PUBMED:16489762 , PUBMED:8196544 , PUBMED:7798143 , PUBMED:7765895 , PUBMED:9503612 , PUBMED:7812114 , PUBMED:10387106 , PUBMED:12177338 , PUBMED:17213192 , PUBMED:9701813 , PUBMED:11931550 , PUBMED:15802252 , PUBMED:15802251 , PUBMED:9784364 , PUBMED:10400588 , PUBMED:2823881 ].

Gene Ontology

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

Domain organisation

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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 353 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 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_meth_N DpnI_C DprA_WH DsrC DsrD DUF1016_N DUF1133 DUF1153 DUF1323 DUF134 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1819 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2513 DUF2582 DUF3116 DUF3253 DUF3853 DUF3860 DUF3908 DUF433 DUF4364 DUF4423 DUF4447 DUF480 DUF4817 DUF5635 DUF573 DUF6088 DUF6262 DUF6362 DUF6432 DUF6462 DUF6471 DUF722 DUF739 DUF742 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_C FokI_N 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_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_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 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 MogR_DNAbind Mor MotA_activ MqsA_antitoxin MRP-L20 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 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 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 RP-C RPA RPA_C 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 Ski_Sno SLIDE Slx4 SMC_Nse1 SMC_ScpB SoPB_HTH SpoIIID SRP19 SRP_SPB STN1_2 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 YdaS_antitoxin 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: Prodom_2003 (release 99.1)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 21
Number in full: 18551
Average length of the domain: 118.20 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 80.57 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.1 23.1
Trusted cut-off 23.1 23.1
Noise cut-off 23.0 23.0
Model length: 121
Family (HMM) version: 21
Download: download the raw HMM for this family

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 FUR domain has been found. There are 70 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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AlphaFold Structure Predictions