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NorR DNA-binding transcriptional dual regulator

Synonyms: NorR
Summary:
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 [6, 7, 8, 9, 10]. It was determined by Genomic SELEX screening that NorR binds strongly only between norR and norVW, and it binds with minor strength between genes such as sad/yneJ and glpF/zapB [4]. It has been classified as a single-target transcription factor [4]. A norR mutant is completely defective with respect to anaerobic NO detoxification [7] and is sensitive to reactive nitrogen intermediates generated from nitroprusside. The norR gene is transcribed divergently from norVW and autoregulated [3].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
NorR Functional   nd nd nd
Evolutionary Family: EBP
TFBs length: 13
TFBs symmetry: inverted-repeat
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
norR
norRp
norR
 


Regulon       
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
NorR,NsrR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[NorR,-](1)
[NorR,+](1)


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 Confidence level (C: Confirmed, S: Strong, W: Weak) References
  NorR repressor norRp nd -45.0 -63.0 norR
attaatgagtAGTCAAAATGACTatcaatcaaa
2832346 2832358 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [2], [2], [3], [4], [5]
  NorR repressor norRp nd -21.0 -39.0 norR
tcaatcaaatGGTCGATATGACAatatctatag
2832322 2832334 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [2], [3], [4], [5]
  NorR repressor norRp nd 1.0 -18.0 norR
caatatctatAGTCAAATTGACAgtgaggcaaa
2832301 2832313 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [2], [3], [4], [5]
  NorR activator norVp Sigma54 -132.0 -169.0 norV, norW
tttgcctcacTGTCAATTTGACTatagatattg
2832301 2832313 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [2], [2], [3], [4], [5], [6], [7], [8]
  NorR activator norVp Sigma54 -111.0 -148.0 norV, norW
ctatagatatTGTCATATCGACCatttgattga
2832322 2832334 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [2], [2], [3], [4], [5], [6], [7], [8]
  NorR activator norVp Sigma54 -87.0 -124.0 norV, norW
tttgattgatAGTCATTTTGACTactcattaat
2832346 2832358 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-GSELEX], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [2], [2], [3], [4], [5], [5], [6], [7], [8]


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




Reference(s)    

 [1] 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

 [2] 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

 [3] 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

 [4] Shimada T., Ogasawara H., Kobayashi I., Kobayashi N., Ishihama A., 2021, Single-Target Regulators Constitute the Minority Group of Transcription Factors in Escherichia coli K-12., Front Microbiol 12:697803

 [5] 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

 [6] 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

 [7] 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

 [8] 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

 [9] 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, 280(41):34599 10.1074/jbc.M506349200

 [10] 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

 [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, 185(6):1757 10.1128/JB.185.6.1757-1767.2003

 [13] 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

 [14] 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, 19(20):5288 10.1093/emboj/19.20.5288

 [15] 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, 283(2):908 10.1074/jbc.M705850200

 [16] 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, 77(5):1278 10.1111/j.1365-2958.2010.07290.x

 [17] D'Autréaux B, Tucker N, Spiro S, Dixon R, 2008, Characterization of the nitric oxide-reactive transcriptional activator NorR., Methods Enzymol, 437(None):235 10.1016/S0076-6879(07)37013-4

 [18] 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

 [19] 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, 186(23):7980 10.1128/JB.186.23.7980-7987.2004

 [20] 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, 38(4):1182 10.1093/nar/gkp1065

 [21] Spiro S, 2007, Regulators of bacterial responses to nitric oxide., FEMS Microbiol Rev, 31(2):193 10.1111/j.1574-6976.2006.00061.x



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