RegulonDB RegulonDB 9.4:Regulon Page

SoxR DNA-binding transcriptional dual regulator

Synonyms: SoxR, SoxR-[2Fe-2S]3+ oxydized, SoxR-[2Fe-2S]2+ reduced
The SoxR protein, for Superoxide Response protein, is negatively autoregulated and controls the transcription of the regulon involved in defense against redox-cycling drugs [7, 8, 9, 10] and in responses to nitric oxide [5, 11, 12, 13, 14, 15, 16, 17, 18, 19]. SoxR belongs to the MerR family and is a homodimer in solution [3, 20].
SoxR contains two essential [2Fe-2S] clusters for its transcriptional activity [21]. Each SoxR polypeptide contains a [2Fe-2S] cluster that senses the oxidants in the cell. Both Fe-SoxR and apo-SoxR bind to the promoter region, but only Fe-SoxR contributes to the activation in its oxidized form [2, 3, 20, 22, 23]. The redox state of the iron-sulfur cluster regulates SoxR activity [1, 4].
Read more >

Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
SoxR     nd nd
SoxR-[2Fe-2S]2+ reduced Non-Functional Covalent Apo [BPP], [GEA], [IDA], [IEP], [IPI], [SM] [1], [2], [3], [4]
SoxR-[2Fe-2S]3+ oxydized Functional Covalent Holo [BPP], [GEA], [IDA], [IEP], [IPI], [SM] [1], [2], [3], [4]
Evolutionary Family: MerR
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: soxR
  Genome position: 4277469-4277933
  Length: 465 bp / 154 aa
Operon name: soxR
TU(s) encoding the TF:
Transcription unit        Promoter

Regulated gene(s) fumC, soxR, soxS
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
Transcription related (2)
activator (2)
repressor (2)
other (mechanical, nutritional, oxidative stress) (2)
detoxification (2)
Read more >
Regulated operon(s) fumAC, soxR, soxS
First gene in the operon(s) fumC, soxR, soxS
Simple and complex regulons AcrR,FNR,Fur,SoxR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

Transcription factor binding sites (TFBSs) arrangements       

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Growth Conditions Evidence (Confirmed, Strong, Weak) References
  SoxR activator fumCp Sigma38 nd nd fumC nd nd [a] [BPP], [GEA] [5]
  SoxR repressor soxRp Sigma70 2.5 -20.5 soxR
4277440 4277457 nd [BPP], [GEA] [3], [6]
  SoxR activator soxSp Sigma70 -25.5 -65.5 soxS
4277440 4277457 [a] [BPP], [GEA] [3], [6]

Growth Condition    

 [a] with paraquat

Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
Promoter-target gene evolutionary conservation


 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [IDA] Inferred from direct assay

 [IEP] Inferred from expression pattern

 [IPI] Inferred from physical interaction

 [SM] Site mutation


 [1] Gaudu P., Moon N., Weiss B., 1997, Regulation of the soxRS oxidative stress regulon. Reversible oxidation of the Fe-S centers of SoxR in vivo., J Biol Chem. 272(8):5082-6

 [2] Gaudu P., Weiss B., 1996, SoxR, a [2Fe-2S] transcription factor, is active only in its oxidized form., Proc Natl Acad Sci U S A. 93(19):10094-8

 [3] Hidalgo E., Bollinger JM., Bradley TM., Walsh CT., Demple B., 1995, Binuclear [2Fe-2S] clusters in the Escherichia coli SoxR protein and role of the metal centers in transcription., J Biol Chem. 270(36):20908-14

 [4] Hidalgo E., Ding H., Demple B., 1997, Redox signal transduction: mutations shifting [2Fe-2S] centers of the SoxR sensor-regulator to the oxidized form., Cell. 88(1):121-9

 [5] Fuentes AM., Diaz-Mejia JJ., Maldonado-Rodriguez R., Amabile-Cuevas CF., 2001, Differential activities of the SoxR protein of Escherichia coli: SoxS is not required for gene activation under iron deprivation., FEMS Microbiol Lett. 201(2):271-5

 [6] Hidalgo E., Leautaud V., Demple B., 1998, The redox-regulated SoxR protein acts from a single DNA site as a repressor and an allosteric activator., EMBO J. 17(9):2629-36

 [7] Greenberg JT., Monach P., Chou JH., Josephy PD., Demple B., 1990, Positive control of a global antioxidant defense regulon activated by superoxide-generating agents in Escherichia coli., Proc Natl Acad Sci U S A. 87(16):6181-5

 [8] Nunoshiba T., Hidalgo E., Amabile Cuevas CF., Demple B., 1992, Two-stage control of an oxidative stress regulon: the Escherichia coli SoxR protein triggers redox-inducible expression of the soxS regulatory gene., J Bacteriol. 174(19):6054-60

 [9] Vasil'eva SV., Stupakova MV., Lobysheva II., Mikoyan VD., Vanin AF., 2001, Activation of the Escherichia coli SoxRS-regulon by nitric oxide and its physiological donors., Biochemistry (Mosc). 66(9):984-8

 [10] Gu M., Imlay JA., 2011, The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide., Mol Microbiol. 79(5):1136-50

 [11] Tsaneva IR., Weiss B., 1990, soxR, a locus governing a superoxide response regulon in Escherichia coli K-12., J Bacteriol. 172(8):4197-205

 [12] Lu C., Bentley WE., Rao G., 2003, Comparisons of oxidative stress response genes in aerobic Escherichia coli fermentations., Biotechnol Bioeng. 83(7):864-70

 [13] Liochev SI., Fridovich I., 1992, Fumarase C, the stable fumarase of Escherichia coli, is controlled by the soxRS regulon., Proc Natl Acad Sci U S A. 89(13):5892-6

 [14] Liochev SI., Hausladen A., Fridovich I., 1999, Nitroreductase A is regulated as a member of the soxRS regulon of Escherichia coli., Proc Natl Acad Sci U S A. 96(7):3537-9

 [15] Demple B., 1999, Genetic responses against nitric oxide toxicity., Braz J Med Biol Res. 32(11):1417-27

 [16] Demple B., Ding H., Jorgensen M., 2002, Escherichia coli SoxR protein: sensor/transducer of oxidative stress and nitric oxide., Methods Enzymol. 348:355-64

 [17] Lo FC., Chen CL., Lee CM., Tsai MC., Lu TT., Liaw WF., Yu SS., 2008, A study of NO trafficking from dinitrosyl-iron complexes to the recombinant E. coli transcriptional factor SoxR., J Biol Inorg Chem. 13(6):961-72

 [18] Manchado M., Michan C., Pueyo C., 2000, Hydrogen peroxide activates the SoxRS regulon in vivo., J Bacteriol. 182(23):6842-4

 [19] Agnez-Lima LF., Di Mascio P., Demple B., Menck CF., 2001, Singlet molecular oxygen triggers the soxRS regulon of Escherichia coli., Biol Chem. 382(7):1071-5

 [20] Hidalgo E., Demple B., 1996, Activation of SoxR-dependent transcription in vitro by noncatalytic or NifS-mediated assembly of [2Fe-2S] clusters into apo-SoxR., J Biol Chem. 271(13):7269-72

 [21] Pomposiello PJ., Demple B., 2001, Redox-operated genetic switches: the SoxR and OxyR transcription factors., Trends Biotechnol. 19(3):109-14

 [22] Ding H., Demple B., 1996, Glutathione-mediated destabilization in vitro of [2Fe-2S] centers in the SoxR regulatory protein., Proc Natl Acad Sci U S A. 93(18):9449-53

 [23] Hidalgo E., Demple B., 1994, An iron-sulfur center essential for transcriptional activation by the redox-sensing SoxR protein., EMBO J. 13(1):138-46

 [24] Lee KL., Singh AK., Heo L., Seok C., Roe JH., 2015, Factors affecting redox potential and differential sensitivity of SoxR to redox-active compounds., Mol Microbiol. 97(5):808-21

 [25] Dietrich LE., Teal TK., Price-Whelan A., Newman DK., 2008, Redox-active antibiotics control gene expression and community behavior in divergent bacteria., Science. 321(5893):1203-6

 [26] Demple B., Amabile-Cuevas CF., 1991, Redox redux: the control of oxidative stress responses., Cell. 67(5):837-9

 [27] Liochev SI., Fridovich I., 2011, Is superoxide able to induce SoxRS?, Free Radic Biol Med. 50(12):1813

 [28] Lo FC., Lee JF., Liaw WF., Hsu IJ., Tsai YF., Chan SI., Yu SS., 2012, The metal core structures in the recombinant Escherichia coli transcriptional factor SoxR., Chemistry. 18(9):2565-77

 [29] Wu J., Weiss B., 1992, Two-stage induction of the soxRS (superoxide response) regulon of Escherichia coli., J Bacteriol. 174(12):3915-20

 [30] Amabile-Cuevas CF., Demple B., 1991, Molecular characterization of the soxRS genes of Escherichia coli: two genes control a superoxide stress regulon., Nucleic Acids Res. 19(16):4479-84

 [31] Nunoshiba T., Hidalgo E., Li Z., Demple B., 1993, Negative autoregulation by the Escherichia coli SoxS protein: a dampening mechanism for the soxRS redox stress response., J Bacteriol. 175(22):7492-4

 [32] Michan C., Manchado M., Pueyo C., 2002, SoxRS down-regulation of rob transcription., J Bacteriol. 184(17):4733-8

 [33] Pomposiello PJ., Koutsolioutsou A., Carrasco D., Demple B., 2003, SoxRS-regulated expression and genetic analysis of the yggX gene of Escherichia coli., J Bacteriol. 185(22):6624-32

 [34] Griffith KL., Shah IM., Wolf RE., 2004, Proteolytic degradation of Escherichia coli transcription activators SoxS and MarA as the mechanism for reversing the induction of the superoxide (SoxRS) and multiple antibiotic resistance (Mar) regulons., Mol Microbiol. 51(6):1801-16

 [35] Giro M., Carrillo N., Krapp AR., 2006, Glucose-6-phosphate dehydrogenase and ferredoxin-NADP(H) reductase contribute to damage repair during the soxRS response of Escherichia coli., Microbiology. 152(Pt 4):1119-28

 [36] Touati D., 2000, Sensing and protecting against superoxide stress in Escherichia coli--how many ways are there to trigger soxRS response?, Redox Rep. 5(5):287-93

 [37] Sakamoto A., Terui Y., Yoshida T., Yamamoto T., Suzuki H., Yamamoto K., Ishihama A., Igarashi K., Kashiwagi K., 2015, Three Members of Polyamine Modulon under Oxidative Stress Conditions: Two Transcription Factors (SoxR and EmrR) and a Glutathione Synthetic Enzyme (GshA)., PLoS One. 10(4):e0124883

 [38] Volkert MR., Landini P., 2001, Transcriptional responses to DNA damage., Curr Opin Microbiol. 4(2):178-85

 [39] Spiro S., 2006, Nitric oxide-sensing mechanisms in Escherichia coli., Biochem Soc Trans. 34(Pt 1):200-2

 [40] Lushchak VI., 2008, [Redox-sensors of microorganisms], Ukr Biokhim Zh. 80(4):25-34

 [41] Demple B., Hidalgo E., Ding H., 1999, Transcriptional regulation via redox-sensitive iron-sulphur centres in an oxidative stress response., Biochem Soc Symp. 64:119-28

 [42] Zheng M., Storz G., 2000, Redox sensing by prokaryotic transcription factors., Biochem Pharmacol. 59(1):1-6

 [43] Kiley PJ., Beinert H., 2003, The role of Fe-S proteins in sensing and regulation in bacteria., Curr Opin Microbiol. 6(2):181-5

 [44] Deng M., Zhu H., Guo J., 2010, [Structure, mechanism and roles of the transcription factor SoxR in bacteria--a review]., Wei Sheng Wu Xue Bao. 50(12):1575-82

 [45] Chiang SM., Schellhorn HE., 2012, Regulators of oxidative stress response genes in Escherichia coli and their functional conservation in bacteria., Arch Biochem Biophys. 525(2):161-9

 [46] Kobayashi K., Fujikawa M., Kozawa T., 2014, Oxidative stress sensing by the iron-sulfur cluster in the transcription factor, SoxR., J Inorg Biochem. 133:87-91