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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 [2, 3, 4]. Two binding sites for CadC, Cad1 and Cad2, have been determined in the cadBA operon. While Cad1 contains an inverted repeat sequence and has a preference for AT-rich regions [5], 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 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 [2]. 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 [2].
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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
CadC Functional   nd nd nd
Evolutionary Family: OmpR
TFBs symmetry: inverted-repeat
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,OmpR
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 Confidence level (C: Confirmed, S: Strong, W: Weak) References
  CadC activator cadBp Sigma70 nd nd cadB, cadA nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [2], [2], [3]
  CadC activator cadCp Sigma70 nd nd cadC nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [3]

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


 [1] Brameyer S., Rosch TC., El Andari J., Hoyer E., Schwarz J., Graumann PL., Jung K., 2019, DNA-binding directs the localization of a membrane-integrated receptor of the ToxR family., Commun Biol 2:4

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

 [3] 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

 [4] 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 10.1128/jb.176.11.3278-3285.1994

 [5] Schlundt A, Buchner S, Janowski R, Heydenreich T, Heermann R, Lassak J, Geerlof A, Stehle R, Niessing D, Jung K, Sattler M, 2017, Structure-function analysis of the DNA-binding domain of a transmembrane transcriptional activator., Sci Rep, 7(1):1051 10.1038/s41598-017-01031-9

 [6] 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 10.1016/j.jmb.2015.05.001

 [7] Martini L, Brameyer S, Hoyer E, Jung K, Gerland U, 2021, Dynamics of chromosomal target search by a membrane-integrated one-component receptor., PLoS Comput Biol, 17(2):e1008680 10.1371/journal.pcbi.1008680

 [8] Rauschmeier M, Schüppel 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 10.1016/j.jmb.2013.09.017

 [9] Tetsch L, Jung K, 2009, The regulatory interplay between membrane-integrated sensors and transport proteins in bacteria., Mol Microbiol, 73(6):982 10.1111/j.1365-2958.2009.06847.x

 [10] Tetsch L, Koller C, Dönhöfer A, Jung K, 2011, Detection and function of an intramolecular disulfide bond in the pH-responsive CadC of Escherichia coli., BMC Microbiol, 11(None):74 10.1186/1471-2180-11-74

 [11] Brameyer S, Hoyer E, Bibinger S, Burdack K, Lassak J, Jung K, 2020, Molecular design of a signaling system influences noise in protein abundance under acid stress in different ?-Proteobacteria., J Bacteriol, None(None):None 10.1128/JB.00121-20

 [12] Leyn SA, Zlamal JE, Kurnasov OV, Li X, Elane M, Myjak L, Godzik M, de Crecy A, Garcia-Alcalde F, Ebeling M, Osterman AL, 2021, Experimental evolution in morbidostat reveals converging genomic trajectories on the path to triclosan resistance., Microb Genom, 7(5):None 10.1099/mgen.0.000553