RegulonDB RegulonDB 10.8:Regulon Page

CueR DNA-binding transcriptional dual regulator

Synonyms: CueR-Ag, CueR-Au, CueR, CueR-Cu+
The "Cu efflux regulator," CueR, regulates genes related to the primary copper homeostasis system [2, 3, 6], which responds to the presence of copper, silver, or gold ions [6, 7]. The Cue system is predominantly active under aerobic conditions []. Oxidative stress and Fe excess, provoked by Zn(II) stress, cause a dysregulation of CueR [5]. The crystal structures of CueR dimers bound to Cu+, Ag+, or Au+ have been solved [1]. Each monomer consists of three domains, an N-terminal DNA-binding domain carrying two helix-turn-helix motifs, a central dimerization domain, and a C-terminal metal-binding domain. The DNA-binding and dimerization domains are characteristic of the MerR family of proteins. The dimerization domain contains a 10-turn α-helix that forms an antiparallel coiled-coil with the helix of the other monomer.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
CueR Non-Functional   Apo [AIFS], [IEP], [IPI] [1], [2]
CueR-Ag Functional Allosteric Holo nd nd
CueR-Au Functional Allosteric Holo nd nd
CueR-Cu+ Functional Allosteric Holo nd nd
Sensing class: External sensing using transported metabolites
Connectivity class: Local Regulator
Gene name: cueR
  Genome position: 513993-514400
  Length: 408 bp / 135 aa
Operon name: cueR
TU(s) encoding the TF:
Transcription unit        Promoter

Regulated gene(s) copA, cueO, moaA, moaB, moaC, moaD, moaE
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
molybdenum (5)
transport (1)
metabolism (1)
other (mechanical, nutritional, oxidative stress) (1)
detoxification (1)
Regulated operon(s) copA, cueO, moaABCDE
First gene in the operon(s) copA, cueO, moaA
Simple and complex regulons CueR
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
  CueR-Cu+ activator copAp Sigma70 -25.0 -57.0 copA 511436 511435 [APIORCISFBSCS], [BPP], [CV(GEA)], [CV(GEA)], [CV(GEA/SM)], [CV(SM)], [GEA], [SM] [2], [3], [4], [5], [6]
  CueR-Cu+ activator cueOp nd -25.0 -63.0 cueO 137020 137019 [APIORCISFBSCS], [BPP], [CV(GEA)], [CV(GEA)], [GEA] [2], [5], [6]
  CueR-Cu+ repressor moaAp1 nd 202.0 -16.0 moaA, moaB, moaC, moaD, moaE
817019 817037 [APIORCISFBSCS], [CV(GEA)], [GEA] [6]

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


 [AIFS] Automated inference of function from sequence

 [IEP] Inferred from expression pattern

 [IPI] Inferred from physical interaction

 [APIORCISFBSCS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [BPP] Binding of purified proteins

 [CV(GEA)] cross validation(GEA)

 [CV(GEA/SM)] cross validation(GEA/SM)

 [CV(SM)] cross validation(SM)

 [GEA] Gene expression analysis

 [SM] Site mutation


 [1] Changela A., Chen K., Xue Y., Holschen J., Outten CE., O'Halloran TV., Mondragon A., 2003, Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR., Science 301(5638):1383-7

 [2] Outten FW., Outten CE., Hale J., O'Halloran TV., 2000, Transcriptional activation of an Escherichia coli copper efflux regulon by the chromosomal MerR homologue, cueR., J Biol Chem 275(40):31024-9

 [3] Petersen C., Moller LB., 2000, Control of copper homeostasis in Escherichia coli by a P-type ATPase, CopA, and a MerR-like transcriptional activator, CopR., Gene 261(2):289-98

 [4] Stoyanov JV., Hobman JL., Brown NL., 2001, CueR (YbbI) of Escherichia coli is a MerR family regulator controlling expression of the copper exporter CopA., Mol Microbiol 39(2):502-11

 [5] Xu Z., Wang P., Wang H., Yu ZH., Au-Yeung HY., Hirayama T., Sun H., Yan A., 2019, Zinc excess increases cellular demand for iron and decreases tolerance to copper in Escherichia coli., J Biol Chem 294(45):16978-16991

 [6] Yamamoto K., Ishihama A., 2005, Transcriptional response of Escherichia coli to external copper., Mol Microbiol 56(1):215-27

 [7] Stoyanov JV., Brown NL., 2003, The Escherichia coli copper-responsive copA promoter is activated by gold., J Biol Chem 278(3):1407-10