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Cbl DNA-binding transcriptional activator

Synonyms: Cbl, Cbl-adenosine 5' phosphosulphate, Cbl-Thiosulphate
Summary:
The transcription factor Cbl, for cysB like, is a regulator involved in the expression of genes required for aliphatic sulfonate utilization and homeostatic response to sulfate starvation [1, 3, 4, 5, 6, 7] Cbl does not require a ligand to binds to its DNA-binding site, but the activity of this protein is negatively regulated by the 5'-phophosulfate cofactor [1]
This protein belongs to the large LysR family of transcriptional regulators and it is positively regulated by CysB, which is similar to Cbl (40% identity) [5, 8] Members of this family have two domains, an N-terminal domain with a helix-turn-helix DNA-binding motif and a large C-terminal domain [2, 5, 8] In systematic studies of oligomerization, it was shown that some members of the LysR family, like Cbl, interact with other members of the family to form heterodimers, but the physiological significance of this is unknown [9]
The crystal structure of the C-terminal regulatory domain of Cbl (2.8Å) has been solved [2] Read more >


Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
Cbl Functional   Apo [BPP], [GEA], [IDA], [IPI], [SM] [1], [2]
Cbl-Thiosulphate Non-Functional Allosteric Holo [BPP], [GEA], [IPI], [SM] [2]
Cbl-adenosine 5' phosphosulphate Non-Functional Allosteric Holo [BPP], [GEA], [IDA], [IPI], [SM] [1], [2]
Evolutionary Family: LysR
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: cbl
  Genome position: 2059964-2060914
  Length: 951 bp / 316 aa
Operon name: cbl
TU(s) encoding the TF:
Transcription unit        Promoter
cbl
cblp


Regulon       
Regulated gene(s) ssuA, ssuB, ssuC, ssuD, ssuE, tauA, tauB, tauC, tauD
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
sulfur metabolism (7)
amines (4)
phosphorous metabolism (2)
ABC superfamily, periplasmic binding component (2)
ABC superfamily ATP binding cytoplasmic component (2)
Read more >
Regulated operon(s) ssuEADCB, tauABCD
First gene in the operon(s) ssuE, tauA
Simple and complex regulons Cbl,CysB
Cbl,CysB,FNR,IHF
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[Cbl,+](2)


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
  Cbl activator ssuEp Sigma70 -54.5 -105.5 ssuE, ssuA, ssuD, ssuC, ssuB
aaagccctttCTTTAGTTTATTTTCAGAAAAAGATACACAAAATTTATATttggaatttt
997598 997637 [BPP], [GEA] [1], [3]
  Cbl activator tauAp nd -91.0 -118.5 tauA, tauB, tauC, tauD
gttagaacggAGTAATTGCATATTTAATCTTTCCTTAGCCGTTTTTTTGCtaagaataaa
385094 385133 [BPP], [GEA] [4]


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

 [IDA] Inferred from direct assay

 [IPI] Inferred from physical interaction

 [SM] Site mutation



Reference(s)    

 [1] Bykowski T., van der Ploeg JR., Iwanicka-Nowicka R., Hryniewicz MM., 2002, The switch from inorganic to organic sulphur assimilation in Escherichia coli: adenosine 5'-phosphosulphate (APS) as a signalling molecule for sulphate excess., Mol Microbiol. 43(5):1347-58

 [2] Stec E., Witkowska-Zimny M., Hryniewicz MM., Neumann P., Wilkinson AJ., Brzozowski AM., Verma CS., Zaim J., Wysocki S., Bujacz GD., 2006, Structural basis of the sulphate starvation response in E. coli: crystal structure and mutational analysis of the cofactor-binding domain of the Cbl transcriptional regulator., J Mol Biol. 364(3):309-22

 [3] van Der Ploeg JR., Iwanicka-Nowicka R., Bykowski T., Hryniewicz MM., Leisinger T., 1999, The Escherichia coli ssuEADCB gene cluster is required for the utilization of sulfur from aliphatic sulfonates and is regulated by the transcriptional activator Cbl., J Biol Chem. 274(41):29358-65

 [4] van der Ploeg JR., Iwanicka-Nowicka R., Kertesz MA., Leisinger T., Hryniewicz MM., 1997, Involvement of CysB and Cbl regulatory proteins in expression of the tauABCD operon and other sulfate starvation-inducible genes in Escherichia coli., J Bacteriol. 179(24):7671-8

 [5] Iwanicka-Nowicka R., Hryniewicz MM., 1995, A new gene, cbl, encoding a member of the LysR family of transcriptional regulators belongs to Escherichia coli cys regulon., Gene. 166(1):11-7

 [6] Kertesz MA., 2000, Riding the sulfur cycle--metabolism of sulfonates and sulfate esters in gram-negative bacteria., FEMS Microbiol Rev. 24(2):135-75

 [7] van der Ploeg JR., Eichhorn E., Leisinger T., 2001, Sulfonate-sulfur metabolism and its regulation in Escherichia coli., Arch Microbiol. 176(1-2):1-8

 [8] Stec E., Witkowska M., Hryniewicz MM., Brzozowski AM., Wilkinson AJ., Bujacz GD., 2004, Crystallization and preliminary crystallographic studies of the cofactor-binding domain of the LysR-type transcriptional regulator Cbl from Escherichia coli., Acta Crystallogr D Biol Crystallogr. 60(Pt 9):1654-7

 [9] Knapp GS., Hu JC., 2010, Specificity of the E. coli LysR-type transcriptional regulators., PLoS One. 5(12):e15189



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