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NorR DNA-binding transcriptional dual regulator

Synonyms: NorR
NorR, "NO reduction and detoxification Regulator," is one of several regulatory proteins, such as Fur, SoxR, and OxyR, that are involved in the response to reactive nitrogen species. Under anaerobic and microaerobic conditions it activates transcription of the norVW operon, encoding a nitric oxide (NO)-reducing flavorubredoxin that detoxifies NO [2, 3, 4, 5, 10]. A norR mutant is completely defective with respect to anaerobic NO detoxification [3] and is sensitive to reactive nitrogen intermediates generated from nitroprusside. The norR gene is transcribed divergently from norVW and autoregulated [9]. It is activated in the absence of oxygen and by nitrite under anaerobic conditions [11]. NorR is a σ54-dependent transcriptional activator [12].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
NorR Functional   [APPH], [IDA], [IEP], [IMP] [1], [2], [3], [4], [5], [6]
Evolutionary Family: EBP
Connectivity class: Local Regulator
Gene name: norR
  Genome position: 2830775-2832289
  Length: 1515 bp / 504 aa
Operon name: norR
TU(s) encoding the TF:
Transcription unit        Promoter

Regulated gene(s) norR, norV, norW
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
detoxification (2)
electron carriers (2)
Transcription related (1)
activator (1)
Regulated operon(s) norR, norVW
First gene in the operon(s) norR, norV
Simple and complex regulons FNR,IHF,NarL,NarP,NorR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

Transcription factor regulation    

Transcription factor binding sites (TFBSs) arrangements

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  NorR repressor norRp nd -45.0 -63.0 norR
2832346 2832358 [AIBSCS], [BPP], [GEA] [6], [7], [8], [9]
  NorR repressor norRp nd -21.0 -39.0 norR
2832322 2832334 [AIBSCS], [BPP], [GEA] [6], [7], [8], [9]
  NorR repressor norRp nd 1.0 -18.0 norR
2832301 2832313 [AIBSCS], [BPP], [GEA] [6], [7], [8], [9]
  NorR activator norVp Sigma54 -132.0 -169.0 norV, norW
2832301 2832313 [AIBSCS], [BPP], [GEA] [2], [3], [4], [6], [7], [8], [9]
  NorR activator norVp Sigma54 -111.0 -148.0 norV, norW
2832322 2832334 [AIBSCS], [BPP], [GEA] [2], [3], [4], [6], [7], [8], [9]
  NorR activator norVp Sigma54 -87.0 -124.0 norV, norW
2832346 2832358 [AIBSCS], [BPP], [GEA] [2], [3], [4], [6], [7], [8], [9]

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


 [APPH] Assay of protein purified to homogeneity

 [IDA] Inferred from direct assay

 [IEP] Inferred from expression pattern

 [IMP] Inferred from mutant phenotype

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis


 [1] D'Autreaux B., Tucker NP., Dixon R., Spiro S., 2005, A non-haem iron centre in the transcription factor NorR senses nitric oxide., Nature 437(7059):769-72

 [2] Gardner AM., Gessner CR., Gardner PR., 2003, Regulation of the nitric oxide reduction operon (norRVW) in Escherichia coli. Role of NorR and sigma54 in the nitric oxide stress response., J Biol Chem 278(12):10081-6

 [3] Gardner AM., Helmick RA., Gardner PR., 2002, Flavorubredoxin, an inducible catalyst for nitric oxide reduction and detoxification in Escherichia coli., J Biol Chem 277(10):8172-7

 [4] Hutchings MI., Mandhana N., Spiro S., 2002, The NorR protein of Escherichia coli activates expression of the flavorubredoxin gene norV in response to reactive nitrogen species., J Bacteriol 184(16):4640-3

 [5] Mukhopadhyay P., Zheng M., Bedzyk LA., LaRossa RA., Storz G., 2004, Prominent roles of the NorR and Fur regulators in the Escherichia coli transcriptional response to reactive nitrogen species., Proc Natl Acad Sci U S A 101(3):745-50

 [6] Tucker NP., D'Autr?aux B., Studholme DJ., Spiro S., Dixon R., 2004, DNA binding activity of the Escherichia coli nitric oxide sensor NorR suggests a conserved target sequence in diverse proteobacteria., J Bacteriol 186(19):6656-60

 [7] Justino MC., Goncalves VM., Saraiva LM., 2005, Binding of NorR to three DNA sites is essential for promoter activation of the flavorubredoxin gene, the nitric oxide reductase of Escherichia coli., Biochem Biophys Res Commun 328(2):540-4

 [8] Tucker N., D'autreaux B., Spiro S., Dixon R., 2005, DNA binding properties of the Escherichia coli nitric oxide sensor NorR: towards an understanding of the regulation of flavorubredoxin expression., Biochem Soc Trans 33(Pt 1):181-3

 [9] Tucker NP., D'autreaux B., Spiro S., Dixon R., 2006, Mechanism of transcriptional regulation by the Escherichia coli nitric oxide sensor NorR., Biochem Soc Trans 34(Pt 1):191-4

 [10] Vicente JB, Teixeira M, 2005, Redox and spectroscopic properties of the Escherichia coli nitric oxide-detoxifying system involving flavorubredoxin and its NADH-oxidizing redox partner., J Biol Chem, 2005 Oct 14

 [11] da Costa PN., Teixeira M., Saraiva LM., 2003, Regulation of the flavorubredoxin nitric oxide reductase gene in Escherichia coli: nitrate repression, nitrite induction, and possible post-transcription control., FEMS Microbiol Lett 218(2):385-93

 [12] Studholme DJ, Dixon R, 2003, Domain architectures of sigma54-dependent transcriptional activators., J Bacteriol, 2003 Mar

 [13] Ho YS, Burden LM, Hurley JH, 2000, Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor., EMBO J, 2000 Oct 16

 [14] Tucker NP, D'Autréaux B, Yousafzai FK, Fairhurst SA, Spiro S, Dixon R, 2008, Analysis of the nitric oxide-sensing non-heme iron center in the NorR regulatory protein., J Biol Chem, 2008 Jan 11

 [15] Bush M, Ghosh T, Tucker N, Zhang X, Dixon R, 2010, Nitric oxide-responsive interdomain regulation targets the ?54-interaction surface in the enhancer binding protein NorR., Mol Microbiol, 2010 Sep

 [16] D'Autréaux B, Tucker N, Spiro S, Dixon R, 2008, Characterization of the nitric oxide-reactive transcriptional activator NorR., Methods Enzymol, 2008

 [17] Baptista JM., Justino MC., Melo AM., Teixeira M., Saraiva LM., 2012, Oxidative stress modulates the nitric oxide defense promoted by Escherichia coli flavorubredoxin., J Bacteriol 194(14):3611-7

 [18] Büsch A, Pohlmann A, Friedrich B, Cramm R, 2004, A DNA region recognized by the nitric oxide-responsive transcriptional activator NorR is conserved in beta- and gamma-proteobacteria., J Bacteriol, 2004 Dec

 [19] Tucker NP, Ghosh T, Bush M, Zhang X, Dixon R, 2010, Essential roles of three enhancer sites in sigma54-dependent transcription by the nitric oxide sensing regulatory protein NorR., Nucleic Acids Res, 2010 Mar

 [20] Spiro S, 2007, Regulators of bacterial responses to nitric oxide., FEMS Microbiol Rev, 2007 Mar