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CusR DNA-binding transcriptional activator

Synonyms: CusR, CusR-phosphorylated
Summary:
CusR, "Cu-sensing regulator", regulates genes related to the copper and silver efflux systems [3, 7]under anaerobic growth and under extreme copper stress in aerobic growth [8] CusR belongs to the two-component system CusS/CusR, which responds to increases in the copper concentration. Both cusR, encoding the response regulator, and cusS, encoding the sensor kinase, are organized in an operon that is located next to and in the opposite direction to an operon whose expression is activated by CusR [3] CusR is able to bind to the cusRS-cusCFBA intergenic region in both its phosphorylated and unphosphorylated forms, but in its unphosphorylated form it binds to many other targets in the genome [9]. The sensor proteins YedW, UhpB, and YedV, which also belong to two-component systems, can activate CusR via signal cross talk [1, 2] This protein binds to the CusR box, which is a palindromic sequence also conserved in other organisms; the sequence is located in the regulatory regions of genes involved in copper-responsive systems and is regulated by proteins homologous to CusR [3] In the whole genome of Escherichia coli, only one copper box has been identified [2] CusR is not an essential protein [10]. Reviews: [11, 12]. Read more >


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
CusR Non-Functional   Apo [EXP-IDA], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IPI] S [1], [2]
CusR-phosphorylated Functional Covalent Holo [EXP-IDA], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IPI] S [1], [2]
Evolutionary Family: OmpR
TFBs length: 22
Sensing class: External-Two-component systems
Connectivity class: Local Regulator
Gene name: cusR
  Genome position: 594760-595443
  Length: 684 bp / 227 aa
Operon name: cusRS
TU(s) encoding the TF:
Transcription unit        Promoter
cusRS
cusRp


Regulon       
Regulated gene(s) cusA, cusB, cusC, cusF, cusR, cusS, cyoA, cyoB, cyoC, cyoD, cyoE, hiuH
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
membrane (7)
aerobic respiration (5)
electron acceptors (4)
Oxidoreduction-driven Active Transporters (3)
Porters (Uni-, Sym- and Antiporters) (1)
Read more >
Regulated operon(s) cusCFBA, cusRS, cyoABCDE, hiuH
First gene in the operon(s) cusC, cusR, cyoA, hiuH
Simple and complex regulons ArcA,CRP,Cra,CusR,FNR,Fis,Fur,GadE,HprR,PdhR
CusR,HprR,PhoB
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[CusR,+](4)


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
  CusR-phosphorylated activator cusCp Sigma70 -53.5 -80.5 cusC, cusF, cusB, cusA
tattggcaaaATGACAATTTTGTCATTtttctgtcac
 595512 595528 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [2], [2], [3], [3], [4], [4], [5], [6]
  CusR-phosphorylated activator cusRp Sigma70 -57.5 -76.5 cusR, cusS
gtgacagaaaAATGACAAAATTGTCATtttgccaata
 595512 595528 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [2], [2], [3], [3], [4], [5], [6]
  CusR-phosphorylated activator cyoAp Sigma70 69.5 26.5 cyoA, cyoB, cyoC, cyoD, cyoE
tcaggaaataCAATAAAAGTTTGGGATggttgtcatt
 451577 451593 [COMP-HINF-SIMILAR-TO-CONSENSUS] W [6], [6]
  CusR-phosphorylated activator hiuHp Sigma70 38.5 -78.5 hiuH
agcctggttcATTACAAAATTGTAATGctgctgtaag
 2038870 2038886 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [4], [4], [6], [6]


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


Evidence    

 [EXP-IDA] Inferred from direct assay

 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] Binding of purified proteins

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [EXP-IPI] Inferred from physical interaction

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [COMP-AINF-SIMILAR-TO-CONSENSUS] Automated inference based on similarity to consensus sequences


Reference(s)    

 [1] Yamamoto K., Hirao K., Oshima T., Aiba H., Utsumi R., Ishihama A., 2005, Functional characterization in vitro of all two-component signal transduction systems from Escherichia coli., J Biol Chem 280(2):1448-56

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

 [3] Munson GP., Lam DL., Outten FW., O'Halloran TV., 2000, Identification of a copper-responsive two-component system on the chromosome of Escherichia coli K-12., J Bacteriol 182(20):5864-71

 [4] Urano H., Yoshida M., Ogawa A., Yamamoto K., Ishihama A., Ogasawara H., 2017, Cross-regulation between two common ancestral response regulators, HprR and CusR, in Escherichia coli., Microbiology 163(2):243-252

 [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] Urano H., Umezawa Y., Yamamoto K., Ishihama A., Ogasawara H., 2015, Cooperative regulation of the common target genes between H2O2-sensing YedVW and Cu2+-sensing CusSR in Escherichia coli., Microbiology 161(Pt 4):729-38

 [7] Franke S., Grass G., Nies DH., 2001, The product of the ybdE gene of the Escherichia coli chromosome is involved in detoxification of silver ions., Microbiology 147(Pt 4):965-72

 [8] Outten FW, Huffman DL, Hale JA, O'Halloran TV, 2001, The independent cue and cus systems confer copper tolerance during aerobic and anaerobic growth in Escherichia coli., J Biol Chem, 276(33):30670 10.1074/jbc.M104122200

 [9] 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

 [10] Miyake Y., Yamamoto K., 2020, Epistatic Effect of Regulators to the Adaptive Growth of Escherichia coli., Sci Rep 10(1):3661

 [11] Rademacher C, Masepohl B, 2012, Copper-responsive gene regulation in bacteria., Microbiology (Reading), 158(Pt 10):2451 10.1099/mic.0.058487-0

 [12] Giachino A, Waldron KJ, 2020, Copper tolerance in bacteria requires the activation of multiple accessory pathways., Mol Microbiol, 114(3):377 10.1111/mmi.14522


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