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HprR DNA-binding transcriptional dual regulator

Synonyms: HprR-phosphorylated, HprR
Based on Genomic SELEX screening, the two-component system (TCS) HprR (previously called YedVW) has been characterized, and five operons, cyoABCDE, yedVW, hiuH, cusSR, and cusCFBA, were predicted to be under the direct control of this TCS; however, its regulatory role has only been examined for the hiuH gene [1] The HprSR and CusSR TCSs form a unique regulation system, where both TCSs recognize the same DNA sequence for binding and they cooperate in regulating the same set of target genes and promoter [1], with different affinities [2]. However, the two TCSs recognize different environmental signals for activation, with YedVW sensing H2O2 and CusSR sensing Cu(II) [1] Cross talk occurs between CusSR and HprSR at different stages [2]. The Cys165 residue in the transmembrane region is responsible for sensing H2O2 [2]. YedW is 51% similar to CusR [3] YedVW and CusSR are conserved in a wide variety of bacterial species, indicating that a common evolutionary origin is probable [4] Overproduction causes a drug resistance phenotype [5].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
HprR Non-Functional   Apo nd nd
HprR-phosphorylated Functional   Holo nd nd
Evolutionary Family: OmpR
Sensing class: External-Two-component systems
Connectivity class: Local Regulator
Gene name: hprR
  Genome position: 2038152-2038823
  Length: 672 bp / 223 aa
Operon name: hprRS
TU(s) encoding the TF:
Transcription unit        Promoter

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)
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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
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
  HprR-phosphorylated activator cusCp Sigma70 -53.5 -80.5 cusC, cusF, cusB, cusA
595511 595529 [APIORCISFBSCS], [APIORCISFBSCS], [BPP] [1], [2]
  HprR-phosphorylated activator cusRp Sigma70 -57.5 -76.5 cusR, cusS
595511 595529 [APIORCISFBSCS], [BPP] [1]
  HprR-phosphorylated repressor cyoAp Sigma70 69.5 26.5 cyoA, cyoB, cyoC, cyoD, cyoE
451576 451594 [GEA], [APIORCISFBSCS] [1]
  HprR-phosphorylated activator hiuHp Sigma70 38.5 -78.5 hiuH
2038869 2038887 [GEA], [APIORCISFBSCS], [BPP] [1], [2]

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


 [1] 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

 [2] 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

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

 [4] Bouzat JL, Hoostal MJ, 2013, Evolutionary analysis and lateral gene transfer of two-component regulatory systems associated with heavy-metal tolerance in bacteria., J Mol Evol, 76(5):267 10.1007/s00239-013-9558-z

 [5] Hirakawa H., Nishino K., Hirata T., Yamaguchi A., 2003, Comprehensive studies of drug resistance mediated by overexpression of response regulators of two-component signal transduction systems in Escherichia coli., J Bacteriol 185(6):1851-6

 [6] Hirakawa H., Nishino K., Yamada J., Hirata T., Yamaguchi A., 2003, Beta-lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli., J Antimicrob Chemother 52(4):576-82

 [7] Gennaris A, Ezraty B, Henry C, Agrebi R, Vergnes A, Oheix E, Bos J, Leverrier P, Espinosa L, Szewczyk J, Vertommen D, Iranzo O, Collet JF, Barras F, 2015, Repairing oxidized proteins in the bacterial envelope using respiratory chain electrons., Nature, 528(7582):409 10.1038/nature15764

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