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CysB DNA-binding transcriptional dual regulator

Synonyms: CysB-N-acetyl-L-serine, CysB-Sulphide, CysB-Thiosulfate, CysB, CysB-O-acetyl-L-serine
Summary:
The transcription factor CysB, for "Cysteine B," is negatively autoregulated [3, 12] this regulator also controls the transcription of the operon involved in novobiocin resistance [12, 13]and transcription of genes involved in sulfur utilization and sulfonate-sulfur catabolism via cysteine biosynthesis [1, 3, 5, 7, 9, 16, 18, 19, 20] In the presense of N-acetylserine, the inducer molecule of this regulator, DNA binding by CysB tetramers to the target sequences is facilitated [1, 12] but the binding to the repressor site in the cysB regulatory region is prevented [4]. The amino acid sequence of CysB shows homology to members of the LysR family of transcriptional regulators [12, 21, 22, 23] The N-terminal region of this protein comprises a helix-turn-helix DNA-binding motif.
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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
CysB Functional   nd nd nd
CysB-O-acetyl-L-serine Functional Allosteric Holo nd nd nd
CysB-N-acetyl-L-serine Functional Allosteric Holo [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IMP-SITE-MUTATION] S [1]
CysB-Sulphide Non-Functional Allosteric Holo nd nd nd
CysB-Thiosulfate Non-Functional Allosteric Holo nd nd nd
Evolutionary Family: LysR
TFBs length: 42
Sensing class: Sensing external and internal signals
Connectivity class: Local Regulator
Gene name: cysB
  Genome position: 1333855-1334829
  Length: 975 bp / 324 aa
Operon name: cysB
TU(s) encoding the TF:
Transcription unit        Promoter
cysB
cysBp


Regulon       
Regulated gene(s) cbl, cysA, cysB, cysC, cysD, cysH, cysI, cysJ, cysK, cysM, cysN, cysP, cysU, cysW, dgcZ, hslJ, ssuA, ssuB, ssuC, ssuD, ssuE, tauA, tauB, tauC, tauD, tcyJ, tcyP, ybdN, yciW, ygeH, yoaC
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
sulfur metabolism (18)
cysteine (4)
ABC superfamily, periplasmic binding component (4)
ABC superfamily, membrane component (4)
membrane (4)
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Regulated operon(s) cbl, cysB, cysDNC, cysJIH, cysK, cysPUWAM, dgcZ, fliAZ-tcyJ, hslJ, ssuEADCB, tauABCD, tcyP, ybdN, yciW, ygeH, yoaC
First gene in the operon(s) cbl, cysB, cysD, cysJ, cysK, cysP, dgcZ, hslJ, ssuE, tauA, tcyJ, tcyP, ybdN, yciW, ygeH, yoaC
Simple and complex regulons ArcA,CysB,FNR
Cbl,CysB
Cbl,CysB,FNR,IHF
CpxR,CysB
CysB
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[CysB,+](13)
[CysB,-](3)


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
  CysB-O-acetyl-L-serine activator cblp Sigma70 nd nd cbl
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [2]
  CysB repressor cysBp Sigma70 -14.0 -81.0 cysB
ataaatgataTAGTGGTTATAGTTAGCACCTTTTTTATTATTAAATCGTATTAGTCAcccgccaggt
 1333751 1333797 [COMP-HINF-SIMILAR-TO-CONSENSUS] W [3], [4]
  CysB-O-acetyl-L-serine activator cysDp Sigma70 -85.0 -124.0 cysD, cysN, cysC
cggtgccttaAGCACTTTTTGATATTAGCTTTGCCAAATCGTTATTCCGTTAaggaactact
 2876432 2876473 [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS] W [5], [6]
  CysB-O-acetyl-L-serine activator cysJp Sigma70 -55.0 -121.0 cysJ, cysI, cysH
attgctaaaaCAGGTTAGTCGATTTGGTTATTAGTTATCGCTATCCCGTCTTtaatccacac
 2891998 2892039 [COMP-HINF-SIMILAR-TO-CONSENSUS] W [7]
  CysB activator cysKp1 Sigma70 -53.0 -85.0 cysK
ttgcatgtcaTTATTTCCCTTCTGTATATAGATATGCTAAATCCTTACTTCcgcatattct
 2532304 2532344 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IMP-SITE-MUTATION] S [7], [7], [8]
  CysB-O-acetyl-L-serine activator cysPp Sigma70 -66.0 -95.0 cysP, cysU, cysW, cysA, cysM
tgaaccaagtTCTTATTCCCTTTTCAACTTCCAAATCACCAAACGGTATATAaaaccgttac
 2543603 2543644 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [8], [9], [9], [10]
  CysB-O-acetyl-L-serine activator dgcZp Sigma70 -164.5 -193.5 dgcZ
tgggccattaGGGTATTGGGTTATGCTATTTGTCATCCTTTTATTTACGATAAtgcagaggta
 1624023 1624065 [COMP-AINF-SIMILAR-TO-CONSENSUS] W [11], [11]
  CysB-O-acetyl-L-serine repressor hslJp Sigma70 -16.0 -53.0 hslJ
agctgattcaGATAATCCCCAATGACCTTTCATCCTCTATTCTTAAAATAGTcctgagtcag
 1441775 1441816 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [12], [12], [13]
  CysB-O-acetyl-L-serine repressor ssuEp Sigma70 -18.0 -69.0 ssuE, ssuA, ssuD, ssuC, ssuB
cacaaaatttATATTTGGAATTTTCTTGTCTCTCCGACAGACTGACCGAATTgttatcaatg
 997560 997601 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [14], [15], [15]
  CysB-O-acetyl-L-serine activator tauAp nd -202.0 -229.0 tauA, tauB, tauC, tauD
aatataatagTTTTATTATATGTATTGATATTGATAGAAATAATGAAGTAATaaatctcgta
 384982 385023 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [16]
  CysB-O-acetyl-L-serine activator tauAp nd -93.0 -120.0 tauA, tauB, tauC, tauD
attgttagaaCGGAGTAATTGCATATTTAATCTTTCCTTAGCCGTTTTTTTGctaagaataa
 385091 385132 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [16]
  CysB-O-acetyl-L-serine activator tauAp nd -38.0 -65.0 tauA, tauB, tauC, tauD
agaataaaatCATCTGTGCGATAACGACTAATTCTTTTAATGAATGTTTTTAttcctgaata
 385146 385187 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [16]
  CysB activator tcyJp nd nd nd tcyJ
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [17]
  CysB activator tcyPp nd nd nd tcyP
nd
 nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [17]
  CysB-O-acetyl-L-serine activator ybdNp Sigma70 -177.5 -294.5 ybdN
gatttactggGAATAGTCCCCTATGAACTTTATAATTCCTACCGTGACTTTCTtaacttaaaa
 636843 636885 [COMP-AINF-SIMILAR-TO-CONSENSUS] W [11], [11]
  CysB activator yciWp Sigma70 -50.5 -75.5 yciW
ccgttatctcTGTTATACCTTTCTGATATTTGTTATCGCCGATCCGTCTTTCTccccttcccg
 1350162 1350204 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS] W [8], [11], [11]
  CysB-O-acetyl-L-serine activator ygeHp10 Sigma70 -573.5 -788.5 ygeH
cagaaacaatTGAAATATTCAATAATAGTGATGAATGGGCAAATCAACTAAAAcacgcattat
 2991285 2991327 [COMP-AINF-SIMILAR-TO-CONSENSUS] W [11], [11]
  CysB-O-acetyl-L-serine activator yoaCp1 Sigma24 -145.5 -312.5 yoaC
agatattactGTTGATGCTTCTGCTAATTCATTATTTATATTTATAATTTCAAttttatctat
 1893800 1893842 [COMP-AINF-SIMILAR-TO-CONSENSUS] W [11], [11]



High-throughput Transcription factor binding sites (TFBSs)
      

  Functional conformation Function Object name Object type Distance to first Gene Sequence LeftPos RightPos Center Position Growth Condition Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
  CysB-O-acetyl-L-serine activator ariR Transcription-Unit nd
gcataattcgTGATTTTAGCAATAGTGATTCAGGAGGGCCAAACCGAAGAACAgcgacagctg
1216241 1216283 1216261.5 nd [COMP-AINF-SIMILAR-TO-CONSENSUS] nd [11]
  CysB-O-acetyl-L-serine activator yfbR Transcription-Unit nd
gtggcatgcgTGATGTTACCGTGGAAGATATTTACATCGGCAATGGTGTATCGgagcttatcg
2407833 2407875 2407853.5 nd [COMP-AINF-SIMILAR-TO-CONSENSUS] nd [11]


Alignment and PSSM for CysB TFBSs    

Aligned TFBS of CysB   
  Sequence
  GAAAGACGGATCGGCGATAACAAATATCAGAAAGGTATAACAG
  TAAAGACGGGATAGCGATAACTAATAACCAAATCGACTAACCT
  TATATACAGAAGGGAAATAATGACATGCAAGATGGAATAAGGG
  TATATACCGTTTGGTGATTTGGAAGTTGAAAAGGGAATAAGAA
  GAAAGTCACGGTAGGAATTATAAAGTTCATAGGGGACTATTCC
  GAAATTATAAATATAAATAATGAATTAGCAGAAGCATCAACAG
  GAAATATTCAATAATAGTGATGAATGGGCAAATCAACTAAAAC
  GGAATAACGATTTGGCAAAGCTAATATCAAAAAGTGCTTAAGG
  TATCGTAAATAAAAGGATGACAAATAGCATAACCCAATACCCT
  ATTATATGTATTGATATTGATAGAAATAATGAAGTAATAAATC
  TAGCAAAAAAACGGCTAAGGAAAGATTAAATATGCAATTACTC
  CTATTTTAAGAATAGAGGATGAAAGGTCATTGGGGATTATCTG
  GGAATAAAAACATTCATTAAAAGAATTAGTCGTTATCGCACAG
  ACAATTCGGTCAGTCTGTCGGAGAGACAAGAAAATTCCAAATA

Position weight matrix (PWM). CysB matrix-quality result    
A	2	9	9	11	1	9	5	6	5	8	7	4	5	4	2	7	9	2	7	9	2	8	11	12	4	6	2	4	10	7	8	11	5	1	2	10	6	0	11	11	4	5	2
C	1	1	0	2	0	0	6	2	2	0	2	2	0	0	5	1	0	0	1	0	4	0	0	1	0	0	1	7	3	0	1	0	1	3	3	0	6	2	1	1	7	3	4
G	6	2	1	0	4	0	0	4	6	3	1	1	6	7	4	4	3	1	4	3	3	4	3	1	4	2	3	3	1	2	3	3	3	9	6	1	0	1	0	0	2	2	6
T	5	2	4	1	9	5	3	2	1	3	4	7	3	3	3	2	2	11	2	2	5	2	0	0	6	6	8	0	0	5	2	0	5	1	3	3	2	11	2	2	1	4	2

Consensus    
;	consensus.strict             	gaaatacagaatggcaataacaaAtatcaaaaaGgactaacag
;	consensus.strict.rc          	CTGTTAGTCCTTTTTGATATTTGTTATTGCCATTCTGTATTTC
;	consensus.IUPAC              	kaaakwmrrratrgsrrtrrbrrAkwksmwrrdSsamtaacms
;	consensus.IUPAC.rc           	SKGTTAKTSSHYYWKSMWMTYYVYYAYYSCYATYYYKWMTTTM
;	consensus.regexp             	[gt]aaa[gt][at][ac][ag][ag][ag]at[ag]g[cg][ag][ag]t[ag][ag][cgt][ag][ag]A[gt][at][gt][cg][ac][at][ag][ag][agt][CG][cg]a[ac]taac[ac][cg]
;	consensus.regexp.rc          	[CG][GT]GTTA[GT]T[CG][CG][ACT][CT][CT][AT][GT][CG][AC][AT][AC]T[CT][CT][ACG][CT][CT]A[CT][CT][CG]C[CT]AT[CT][CT][CT][GT][AT][AC]TTT[AC]

PWM logo   


 


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


Evidence    

 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] Binding of purified proteins

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [EXP-IMP-SITE-MUTATION] Site mutation

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS] Binding of cellular extracts

 [COMP-AINF-SIMILAR-TO-CONSENSUS] Automated inference based on similarity to consensus sequences


Reference(s)    

 [1] Lochowska A., Iwanicka-Nowicka R., Plochocka D., Hryniewicz MM., 2001, Functional dissection of the LysR-type CysB transcriptional regulator. Regions important for DNA binding, inducer response, oligomerization, and positive control., J Biol Chem 276(3):2098-107

 [2] 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

 [3] Jagura-Burdzy G., Hulanicka D., 1981, Use of gene fusions to study expression of cysB, the regulatory gene of the cysteine regulon., J Bacteriol 147(3):744-51

 [4] Ostrowski J., Kredich NM., 1991, Negative autoregulation of cysB in Salmonella typhimurium: in vitro interactions of CysB protein with the cysB promoter., J Bacteriol 173(7):2212-8

 [5] Kredich NM., 1992, The molecular basis for positive regulation of cys promoters in Salmonella typhimurium and Escherichia coli., Mol Microbiol 6(19):2747-53

 [6] Leyh TS., Vogt TF., Suo Y., 1992, The DNA sequence of the sulfate activation locus from Escherichia coli K-12., J Biol Chem 267(15):10405-10

 [7] Monroe RS., Ostrowski J., Hryniewicz MM., Kredich NM., 1990, In vitro interactions of CysB protein with the cysK and cysJIH promoter regions of Salmonella typhimurium., J Bacteriol 172(12):6919-29

 [8] Liu H., Hou Y., Wang Y., Li Z., 2020, Enhancement of Sulfur Conversion Rate in the Production of l-Cysteine by Engineered Escherichia coli., J Agric Food Chem 68(1):250-257

 [9] Lochowska A., Iwanicka-Nowicka R., Zaim J., Witkowska-Zimny M., Bolewska K., Hryniewicz MM., 2004, Identification of activating region (AR) of Escherichia coli LysR-type transcription factor CysB and CysB contact site on RNA polymerase alpha subunit at the cysP promoter., Mol Microbiol 53(3):791-806

 [10] Otsuka J., Watanabe H., Mori KT., 1996, Evolution of transcriptional regulation system through promiscuous coupling of regulatory proteins with operons; suggestion from protein sequence similarities in Escherichia coli., J Theor Biol 178(2):183-204

 [11] Kawano Y., Ohtsu I., Takumi K., Tamakoshi A., Nonaka G., Funahashi E., Ihara M., Takagi H., 2015, Enhancement of L-cysteine production by disruption of yciW in Escherichia coli., J Biosci Bioeng 119(2):176-9

 [12] Jovanovic M., Lilic M., Savic DJ., Jovanovic G., 2003, The LysR-type transcriptional regulator CysB controls the repression of hslJ transcription in Escherichia coli., Microbiology 149(Pt 12):3449-59

 [13] Lilic M., Jovanovic M., Jovanovic G., Savic DJ., 2003, Identification of the CysB-regulated gene, hslJ, related to the Escherichia coli novobiocin resistance phenotype., FEMS Microbiol Lett 224(2):239-46

 [14] 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

 [15] 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

 [16] 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

 [17] Chonoles Imlay KR., Korshunov S., Imlay JA., 2015, Physiological Roles and Adverse Effects of the Two Cystine Importers of Escherichia coli., J Bacteriol 197(23):3629-44

 [18] Leyh TS., Taylor JC., Markham GD., 1988, The sulfate activation locus of Escherichia coli K12: cloning, genetic, and enzymatic characterization., J Biol Chem 263(5):2409-16

 [19] van der Ploeg JR, Eichhorn E, Leisinger T, 2001, Sulfonate-sulfur metabolism and its regulation in Escherichia coli., Arch Microbiol, 176(1-2):1 10.1007/s002030100298

 [20] Rakonjac J, Milic M, Savic DJ, 1991, cysB and cysE mutants of Escherichia coli K12 show increased resistance to novobiocin., Mol Gen Genet, 228(1-2):307 10.1007/BF00282481

 [21] Tei H., Watanabe K., Murata K., Kimura A., 1990, Analysis of the Escherichia coli K-12 cysB gene and its product using the method of gene fusion., Biochem Biophys Res Commun 167(3):962-9

 [22] Ostrowski J., Jagura-Burdzy G., Kredich NM., 1987, DNA sequences of the cysB regions of Salmonella typhimurium and Escherichia coli., J Biol Chem 262(13):5999-6005

 [23] Tyrrell R, Verschueren KH, Dodson EJ, Murshudov GN, Addy C, Wilkinson AJ, 1997, The structure of the cofactor-binding fragment of the LysR family member, CysB: a familiar fold with a surprising subunit arrangement., Structure, 5(8):1017 10.1016/s0969-2126(97)00254-2

 [24] Lamark T., Kaasen I., Eshoo MW., Falkenberg P., McDougall J., Strom AR., 1991, DNA sequence and analysis of the bet genes encoding the osmoregulatory choline-glycine betaine pathway of Escherichia coli., Mol Microbiol 5(5):1049-64


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