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Mlc DNA-binding transcriptional repressor

Synonyms: Mlc, Mlc-EIIGlC
Summary:
DgsA, better known as Mlc, "makes large colonies," [11]is a transcriptional dual regulator that controls the expression of a number of genes encoding enzymes of the Escherichia coli phosphotransferase (PTS) and phosphoenolpyruvate (PEP) systems [12] It also regulates genes involved in the uptake of glucose [8] It is considered a global regulator of carbohydrate metabolism [1, 13]. In addition, Mlc regulates expression of the MalT transcriptional regulator, the activator of the maltose regulon [1]. Mlc repressor function is disabled by binding of Mlc to an actively-transported and dephosphorylated form of PtsG (EIICBGlc) [3] The membrane-bound part of EIICBGlc is essential for Mlc inactivation [].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
Mlc Functional   Apo [APPH], [BCE], [BPP], [IEP], [IPI] [1], [2], [3], [4], [5], [6], [7]
Mlc-EIIGlC Non-Functional Allosteric Holo nd nd
Evolutionary Family: ROK
Connectivity class: Local Regulator
Gene name: mlc
  Genome position: 1667344-1668564
  Length: 1221 bp / 406 aa
Operon name: mlc-ynfK
TU(s) encoding the TF:
Transcription unit        Promoter
mlc
mlcp1
mlc-ynfK
mlcp2
Gene name: ptsG
  Genome position: 1157869-1159302
  Length: 1434 bp / 477 aa
Operon name: ptsG
TU(s) encoding the TF:
Transcription unit        Promoter
ptsG
ptsGp1
ptsG
ptsGp2


Regulon       
Regulated gene(s) crr, malT, manX, manY, manZ, mlc, ptsG, ptsH, ptsI, ynfK
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
carbon compounds (8)
Phosphotransferase Systems (PEP-dependent PTS) (5)
membrane (4)
Transcription related (2)
operon (2)
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Regulated operon(s) malT, manXYZ, mlc-ynfK, ptsG, ptsHI-crr
First gene in the operon(s) malT, manX, mlc, mlc, ptsG, ptsG, ptsH
Simple and complex regulons ArcA,CRP,Fis,Mlc,SoxS
CRP,Cra,Mlc,NagC
CRP,Lrp,Mlc
CRP,Mlc
CRP,Mlc,NagC
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[Mlc,-](7)


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 (Confirmed, Strong, Weak) References
  Mlc repressor malTp Sigma70 12.0 -50.0 malT
ccttataaccATTAATTACGAAGCGCAAAAAAAataatatttc
3553024 3553046 [BCE], [GEA], [HIBSCS] [1], [8]
  Mlc repressor manXp Sigma70 -79.0 -194.0 manX, manY, manZ
tgtgacaaggATATTTTACCTTTCGAAATTTCTgctaatcgaa
1901843 1901865 [BCE], [GEA] [5]
  Mlc repressor manXp Sigma70 -13.0 -128.0 manX, manY, manZ
cataaaataaTTTTTTCGATATCTAAAATAAATcgcgaaacgc
1901909 1901931 [BCE], [GEA] [5]
  Mlc repressor mlcp1 Sigma70 16.0 -24.0 mlc
catactccctATATTTTCGCGCTCCGAAATAATctgtaggcta
1668577 1668599 [BCE], [GEA], [HIBSCS] [1], [8], [9]
  Mlc repressor mlcp2 Sigma70, Sigma32 4.0 -24.0 mlc, ynfK
catactccctATATTTTCGCGCTCCGAAATAATctgtaggcta
1668577 1668599 [BCE], [GEA], [HIBSCS] [1], [8], [9]
  Mlc repressor ptsGp1 nd -6.0 -109.0 ptsG
tggcactgaaTTATTTTACTCTGTGTAATAAATaaagggcgct
1157749 1157771 [BPP], [GEA], [HIBSCS] [6], [8], [10]
  Mlc repressor ptsGp2 Sigma70 -35.0 -278.0 ptsG
gttgaatgagTTTTTTTAAAGCTCGTAATTAATggctaaaacg
1157580 1157602 [BPP], [GEA], [HIBSCS] [6], [8]
  Mlc repressor ptsHp4 Sigma32, Sigma70 13.0 -251.0 ptsH, ptsI, crr
aaccagactaATTATTTTGATGCGCGAAATTAAtcgttacagg
2533502 2533524 [BPP], [GEA], [HIBSCS] [2], [7], [8]


Alignment and PSSM for Mlc TFBSs    

Aligned TFBS of Mlc   
  Sequence
  TTTTTTTAAAGCTCGTAATTAAT
  TTATTTTACTCTGTGTAATAAAT
  TTATTTCGGAGCGCGAAAATATA
  ATATTTTACCTTTCGAAATTTCT
  TTATTTTAGATATCGAAAAAATT
  TTATTTTGATGCGCGAAATTAAT
  TTTTTTTGCGCTTCGTAATTAAT

Position weight matrix (PWM).   
A	1	0	5	0	0	0	0	4	2	3	0	1	0	0	0	4	7	7	2	2	6	4	1
C	0	0	0	0	0	0	1	0	3	1	2	3	0	6	0	0	0	0	0	0	0	1	0
G	0	0	0	0	0	0	0	3	2	1	3	0	3	0	7	0	0	0	0	0	0	0	0
T	6	7	2	7	7	7	6	0	0	2	2	3	4	1	0	3	0	0	5	5	1	2	6

PWM logo   


 


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


Evidence    

 [APPH] Assay of protein purified to homogeneity

 [BCE] Binding of cellular extracts

 [BPP] Binding of purified proteins

 [IEP] Inferred from expression pattern

 [IPI] Inferred from physical interaction

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences



Reference(s)    

 [1] Decker K., Plumbridge J., Boos W., 1998, Negative transcriptional regulation of a positive regulator: the expression of malT, encoding the transcriptional activator of the maltose regulon of Escherichia coli, is negatively controlled by Mlc., Mol Microbiol 27(2):381-90

 [2] Kim SY., Nam TW., Shin D., Koo BM., Seok YJ., Ryu S., 1999, Purification of Mlc and analysis of its effects on the pts expression in Escherichia coli., J Biol Chem 274(36):25398-402

 [3] Lee SJ., Boos W., Bouche JP., Plumbridge J., 2000, Signal transduction between a membrane-bound transporter, PtsG, and a soluble transcription factor, Mlc, of Escherichia coli., EMBO J 19(20):5353-61

 [4] Nam TW., Jung HI., An YJ., Park YH., Lee SH., Seok YJ., Cha SS., 2008, Analyses of Mlc-IIBGlc interaction and a plausible molecular mechanism of Mlc inactivation by membrane sequestration., Proc Natl Acad Sci U S A 105(10):3751-6

 [5] Plumbridge J., 1998, Control of the expression of the manXYZ operon in Escherichia coli: Mlc is a negative regulator of the mannose PTS., Mol Microbiol 27(2):369-80

 [6] Plumbridge J., 1998, Expression of ptsG, the gene for the major glucose PTS transporter in Escherichia coli, is repressed by Mlc and induced by growth on glucose., Mol Microbiol 29(4):1053-63

 [7] Tanaka Y., Kimata K., Inada T., Tagami H., Aiba H., 1999, Negative regulation of the pts operon by Mlc: mechanism underlying glucose induction in Escherichia coli., Genes Cells 4(7):391-9

 [8] Plumbridge J., 2001, DNA binding sites for the Mlc and NagC proteins: regulation of nagE, encoding the N-acetylglucosamine-specific transporter in Escherichia coli., Nucleic Acids Res 29(2):506-14

 [9] Shin D., Lim S., Seok YJ., Ryu S., 2001, Heat shock RNA polymerase (E sigma(32)) is involved in the transcription of mlc and crucial for induction of the Mlc regulon by glucose in Escherichia coli., J Biol Chem 276(28):25871-5

 [10] Shin D., Cho N., Heu S., Ryu S., 2003, Selective regulation of ptsG expression by Fis. Formation of either activating or repressing nucleoprotein complex in response to glucose., J Biol Chem 278(17):14776-81

 [11] Hosono K., Kakuda H., Ichihara S., 1995, Decreasing accumulation of acetate in a rich medium by Escherichia coli on introduction of genes on a multicopy plasmid., Biosci Biotechnol Biochem 59(2):256-61

 [12] Plumbridge J., 2002, Regulation of gene expression in the PTS in Escherichia coli: the role and interactions of Mlc., Curr Opin Microbiol 5(2):187-93

 [13] Kimata K., Inada T., Tagami H., Aiba H., 1998, A global repressor (Mlc) is involved in glucose induction of the ptsG gene encoding major glucose transporter in Escherichia coli., Mol Microbiol 29(6):1509-19

 [14] Schiefner A., Gerber K., Seitz S., Welte W., Diederichs K., Boos W., 2005, The crystal structure of Mlc, a global regulator of sugar metabolism in Escherichia coli., J Biol Chem 280(32):29073-9

 [15] Cho S., Shin D., Ji GE., Heu S., Ryu S., 2005, High-level recombinant protein production by overexpression of Mlc in Escherichia coli., J Biotechnol 119(2):197-203

 [16] Becker AK., Zeppenfeld T., Staab A., Seitz S., Boos W., Morita T., Aiba H., Mahr K., Titgemeyer F., Jahreis K., 2006, YeeI, a Novel Protein Involved in Modulation of the Activity of the Glucose-Phosphotransferase System in Escherichia coli K-12., J Bacteriol 188(15):5439-49



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