|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 . 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].
SoxR contains two critical amino acids around the [2Fe-2S] binding site (RL126R/V130P) and also R127L and P131V substitutions in EcSoxR, which cause a more electropositive environment around [2Fe-2S], making oxidation more difficult .Read more >
It has long been known that SoxR senses superoxide [20, 25, 26]; however, Gu and Imlay (2011) concluded that SoxR actually senses redox-cycling agents . But Liochev and Fridovich reported that the superoxide is indeed sensed by SoxR . The metal core structural and redox states of the metal active sites of SoxR in the presence and absence of O2 and/or NO have been determined .
SoxR and SoxS are two transcription factors that govern a set of genes  in which the two regulators act sequentially [8, 30, 31, 32, 33, 34, 35]. SoxR induces soxS expression, and SoxS, in turn, activates transcription of genes of the regulon .
Under oxidative stress conditions, translation of soxR is increased by the presence of polyamines. The increase is dependent on the suboptimal placement of the Shine-Dalgarno region upstream of the soxR open reading frame .
Reviews: [21, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46]
|Sensing class:||Using internal synthesized signals|
|Connectivity class:||Local Regulator|
|Length:||465 bp / 154 aa|
|TU(s) encoding the TF:||
|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)
other (mechanical, nutritional, oxidative stress) (2)
soxR, soxSRead more >
|Regulated operon(s)||fumAC, soxR, soxS|
|First gene in the operon(s)||fumC, soxR, soxS|
|Simple and complex regulons|
|Simple and complex regulatory phrases||
Regulatory phrase (List of promoters regulated by the phrase)
|Functional conformation||Function||Promoter||Sigma factor||Central Rel-Pos||Distance to first Gene||Genes||Sequence||LeftPos||RightPos||Growth Conditions||Evidence (Confirmed, Strong, Weak)||References|
|4277440||4277457||nd||[BPP], [GEA]||, |
|4277440||4277457||[a]||[BPP], [GEA]||, |
[a] with paraquat
|Evolutionary conservation of regulatory elements|
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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