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CadC DNA-binding transcriptional activator

Synonyms: CadC
Summary:
CadC is a metal-sensitive transcriptional activator that regulates the expression of genes involved in cadaverine synthesis and excretion under low external pH and high concentrations of lysine [1, 2, 3].
Two binding sites for CadC, Cad1 and Cad2, have been determined in the cadBA operon. While Cad1 contains an inverted repeat sequence, Cad2 lacks either an inverted repeat or a palindromic sequence. Both binding sites are necessary for cadBA activation. Under aerobic conditions, H-NS represses the cadBA operon. Upon binding to Cad1, CadC releases the bound H-NS molecules, dissolving the H-NS repressor complex and allowing RNA polymerase binding. Transcription of cadBA is finally activated once a molecule of CadC binds to Cad2 [1].
CadC is an integral membrane protein that belongs to the ToxR-like family of transcriptional activators. It features a cytoplasmic DNA-binding N-terminal domain, a transmembrane domain, and a periplasmic C-terminal domain [1]. Based on two-hybrid analysis, CadC forms stable dimers in a stimulus- and linker-dependent manner, interacting only at pH 6.8; in addition, lysine is required for transducing the pH-dependent response of the periplasmic sensor into a structural rearrangement that facilitates dimerization of the cytoplasmic CadC DNA-binding domain [4].
In the absence of lysine, LysP regulates CadC negatively [3].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
CadC     nd nd
Evolutionary Family: OmpR
Sensing class: External sensing using transported metabolites
Connectivity class: Local Regulator
Gene name: cadC
  Genome position: 4360396-4361934
  Length: 1539 bp / 512 aa
Operon name: cadC
TU(s) encoding the TF:
Transcription unit        Promoter
cadC
cadCp


Regulon       
Regulated gene(s) cadA, cadB, cadC
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
pH (1)
Porters (Uni-, Sym- and Antiporters) (1)
membrane (1)
amino acids (1)
Transcription related (1)
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Regulated operon(s) cadBA, cadC
First gene in the operon(s) cadB, cadC
Simple and complex regulons ArcA,CadC,GadX,H-NS,Lrp,RcsB
CadC,FNR,H-NS,LeuO,MlrA
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
  CadC activator cadBp Sigma70 nd nd cadB, cadA nd nd [BPP], [GEA] [1], [2]
  CadC activator cadCp Sigma70 nd nd cadC nd nd [GEA] [2]


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


Evidence    

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis



Reference(s)    

 [1] Kuper C., Jung K., 2005, CadC-mediated activation of the cadBA promoter in Escherichia coli., J Mol Microbiol Biotechnol. 10(1):26-39

 [2] Watson N., Dunyak DS., Rosey EL., Slonczewski JL., Olson ER., 1992, Identification of elements involved in transcriptional regulation of the Escherichia coli cad operon by external pH., J Bacteriol. 174(2):530-40

 [3] Neely MN., Dell CL., Olson ER., 1994, Roles of LysP and CadC in mediating the lysine requirement for acid induction of the Escherichia coli cad operon., J Bacteriol. 176(11):3278-85

 [4] Buchner S., Schlundt A., Lassak J., Sattler M., Jung K., 2015, Structural and Functional Analysis of the Signal-Transducing Linker in the pH-Responsive One-Component System CadC of Escherichia coli., J Mol Biol. 427(15):2548-61

 [5] Rauschmeier M., Schuppel V., Tetsch L., Jung K., 2014, New insights into the interplay between the lysine transporter LysP and the pH sensor CadC in Escherichia coli., J Mol Biol. 426(1):215-29

 [6] Tetsch L., Jung K., 2009, The regulatory interplay between membrane-integrated sensors and transport proteins in bacteria., Mol Microbiol. 73(6):982-91

 [7] Tetsch L., Koller C., Donhofer A., Jung K., 2011, Detection and function of an intramolecular disulfide bond in the pH-responsive CadC of Escherichia coli., BMC Microbiol. 11(1):74



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