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SoxR DNA-binding transcriptional dual regulator

Synonyms: SoxR, SoxR-[2Fe-2S]3+ oxydized, SoxR-[2Fe-2S]2+ reduced
Summary:
The SoxR protein, for Superoxide Response protein, is negatively autoregulated and controls the transcription of the regulon involved in defense against redox-cycling drugs |CITS: [1696718][1400156][11703180][21226770]| and in responses to nitric oxide |CITS: [1695893][12889026][1631070][11470373][10097071][10559844][11885291][18449575][11073934][11530938]|. SoxR belongs to the MerR family and is a homodimer in solution |CITS: [7673113][8631739]|.
SoxR contains two essential [2Fe-2S] clusters for its transcriptional activity |CITS: [11179804]|. 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 |CITS: [8790350][8816757][8306957][7673113][8631739]|. The redox state of the iron-sulfur cluster regulates SoxR activity |CITS: [9019397][9030573]|. 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 |CITS: [25998932]|.
It has long been known that SoxR senses superoxide |CITS: [8631739][18755976][1659949]|; however, Gu and Imlay (2011) concluded that SoxR actually senses redox-cycling agents |CITS: [21226770]|. But Liochev and Fridovich reported that the superoxide is indeed sensed by SoxR |CITS: [ 21459140]|. 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 |CITS: [22266921]|.
SoxR and SoxS are two transcription factors that govern a set of genes |CITS: [1317841]| in which the two regulators act sequentially |CITS: [1653416][1400156][8226698][12169597][14594836][15009903][16549675]|.
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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
soxR
soxRp


Regulon       
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)
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Regulated operon(s) fumAC, soxR, soxS
First gene in the operon(s) fumC, soxR, soxS
Simple and complex regulons AcrR,FNR,Fur,SoxR
AcrR,FNR,Fur,SoxR,SoxS
ArcA,CRP,FNR,Fur,MarA,SoxR,SoxS
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[SoxR,-](1)
[SoxR,+](1)


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
gagtataattCCTCAAGTTAACTTGAGGtaaagcgatt
4277440 4277457 nd [BPP], [GEA] [3], [6]
  SoxR activator soxSp Sigma70 -25.5 -65.5 soxS
aatcgctttaCCTCAAGTTAACTTGAGGaattatactc
4277440 4277457 [a] [BPP], [GEA] [3], [6]


Growth Condition    

 [a] Paraquat treatment



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


Evidence    

 [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



Reference(s)    

 [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



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