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CadC DNA-binding transcriptional activator

Synonyms: CadC
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

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,GadE-RcsB,GadX,H-NS,Lrp
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

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


 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis


 [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