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Escherichia coli K-12 substr. MG1655 Polypeptide: CadC DNA-binding transcriptional activator

Gene: cadC Accession Numbers: EG10133 (EcoCyc), b4133, ECK4127

Regulation Summary Diagram: ?

Regulation summary diagram for 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 [Watson92, Neely94, Kuper05].

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 [Kuper05].

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 [Kuper05].

In the absence of lysine, LysP regulates CadC negatively [Neely94]. This inhibition is through intramembrane and perisplasmic contacts under noninducing conditions. Based on site-directed mutagenesis, Asp275 and Asp278 in LysP and Arg265 and Arg268 in CadC were identified as residues for the stimulus-dependent interaction between them [Rauschmeier14].

LysP and CadC interact most strongly at pH7.6 and at lysine concentrations of 1 µM or less, that is, under non-Cad-inducing conditions. This interaction is attenuated under Cad-inducing conditions (low pH, increased lysine levels). The LysP-CadC interaction is mediated via trans-membrane and periplasmic contacts [Rauschmeier14]. Oligomerization of LysP is induced at low pH [Rauschmeier14]. LysP is a trigger transporter [Tetsch09], i.e., a protein that combines regulation and transport functions within the one polypeptide.

At neutral cytoplasmic pH, a disulfide bond is formed in the periplasmic domain of CadC to inactivate it. At low pH, formation of the disulfide bond is prevented, which in turn converts CadC into an active state, but only if lysine is present to inactivate to LysP, the negative regulator of CadC [Tetsch11].

Gene Citations: [Takayama94]

Locations: inner membrane

Map Position: [4,358,419 <- 4,359,957] (93.94 centisomes, 338°)
Length: 1539 bp / 512 aa

Molecular Weight of Polypeptide: 57.813 kD (from nucleotide sequence)

pI: 5.55

Unification Links: ASAP:ABE-0013532 , CGSC:34231 , DIP:DIP-9239N , EchoBASE:EB0131 , EcoGene:EG10133 , EcoliWiki:b4133 , ModBase:P23890 , OU-Microarray:b4133 , PortEco:cadC , Protein Model Portal:P23890 , RefSeq:NP_418557 , RegulonDB:EG10133 , SMR:P23890 , String:511145.b4133 , UniProt:P23890

Relationship Links: InterPro:IN-FAMILY:IPR001867 , InterPro:IN-FAMILY:IPR011991 , InterPro:IN-FAMILY:IPR016032 , PDB:Structure:3LY7 , PDB:Structure:3LY8 , PDB:Structure:3LY9 , PDB:Structure:3LYA , Pfam:IN-FAMILY:PF00486 , Smart:IN-FAMILY:SM00862

In Paralogous Gene Group: 182 (3 members)

Genetic Regulation Schematic: ?

Genetic regulation schematic for cadC

GO Terms:

Biological Process: GO:0006351 - transcription, DNA-templated Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Watson92]
GO:0000160 - phosphorelay signal transduction system Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0006355 - regulation of transcription, DNA-templated Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0003677 - DNA binding Inferred by computational analysis [UniProtGOA11a, GOA01a]
Cellular Component: GO:0005622 - intracellular Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0005886 - plasma membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11a]

MultiFun Terms: information transfer RNA related Transcription related
metabolism carbon utilization amino acids
regulation genetic unit regulated operon
regulation type of regulation transcriptional level activator

Symmetry: Inverted Repeat

Regulated Transcription Units (2 total): ?


Transcription-unit diagram

Transcription-unit diagram

Essentiality data for cadC knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 1]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 2]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 1]

Sequence Features

Protein sequence of CadC DNA-binding transcriptional activator with features indicated

Feature Class Location Citations Comment
Mutagenesis-Variant 120 -> 124
[Ude13, UniProt13]
UniProt: Significantly reduced dependence on EF-P for translation, increased levels of protein in an efp- strain.
Protein-Segment 120 -> 124
UniProt: Poly-Pro; Sequence Annotation Type: compositionally biased region.
Mutagenesis-Variant 121
[Ude13, UniProt13]
UniProt: Reduced dependence on EF-P for translation, increased levels of protein in an efp- strain.
Transmembrane-Region 155 -> 180
UniProt: Helical;; Non-Experimental Qualifier: potential;

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


10/20/97 Gene b4133 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10133; confirmed by SwissProt match.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kuper05: Kuper C, Jung K (2005). "CadC-mediated activation of the cadBA promoter in Escherichia coli." J Mol Microbiol Biotechnol 10(1);26-39. PMID: 16491024

Neely94: 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. PMID: 8195083

Rauschmeier14: 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. PMID: 24056175

Takayama94: Takayama M, Ohyama T, Igarashi K, Kobayashi H (1994). "Escherichia coli cad operon functions as a supplier of carbon dioxide." Mol Microbiol 11(5);913-8. PMID: 8022268

Tetsch09: Tetsch L, Jung K (2009). "The regulatory interplay between membrane-integrated sensors and transport proteins in bacteria." Mol Microbiol 73(6);982-91. PMID: 19708919

Tetsch11: 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. PMID: 21486484

Ude13: Ude S, Lassak J, Starosta AL, Kraxenberger T, Wilson DN, Jung K (2013). "Translation elongation factor EF-P alleviates ribosome stalling at polyproline stretches." Science 339(6115);82-5. PMID: 23239623

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt13: UniProt Consortium (2013). "UniProt version 2013-08 released on 2013-08-01 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Watson92: 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. PMID: 1370290

Other References Related to Gene Regulation

Constantinidou06: Constantinidou C, Hobman JL, Griffiths L, Patel MD, Penn CW, Cole JA, Overton TW (2006). "A reassessment of the FNR regulon and transcriptomic analysis of the effects of nitrate, nitrite, NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to anaerobic growth." J Biol Chem 281(8);4802-15. PMID: 16377617

Krin10: Krin E, Danchin A, Soutourina O (2010). "Decrypting the H-NS-dependent regulatory cascade of acid stress resistance in Escherichia coli." BMC Microbiol 10;273. PMID: 21034467

Neely96: Neely MN, Olson ER (1996). "Kinetics of expression of the Escherichia coli cad operon as a function of pH and lysine." J Bacteriol 178(18);5522-8. PMID: 8808945

Ogasawara10: Ogasawara H, Yamamoto K, Ishihama A (2010). "Regulatory role of MlrA in transcription activation of csgD, the master regulator of biofilm formation in Escherichia coli." FEMS Microbiol Lett 312(2);160-8. PMID: 20874755

Shi95: Shi X, Bennett GN (1995). "Effects of multicopy LeuO on the expression of the acid-inducible lysine decarboxylase gene in Escherichia coli." J Bacteriol 177(3);810-4. PMID: 7836317

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 19.0 on Thu Aug 27, 2015, BIOCYC14A.