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NagC DNA-binding transcriptional dual regulator

Synonyms: NagC, NagC-N-acetyl-D-glucosamine-6-phosphate
Summary:
The NagC, N-acetylglucosamine, transcriptional dual regulator participates in regulating the phosphotransferase system (PTS) [16] Its function is to coordinate the biosynthesis of the amino sugars, D-glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) with their catabolism [1, 4, 10, 17].
The specific inducer for NagC is GlcNAc-6-P, the product of GlcNAc transport by the PTS [1, 17] NagC is displaced from its DNA targets by interacting with GlcNAc-6-P [1]
Based on the structure of Mlc DNA-binding transcriptional repressor, models for the three-dimensional structure of NagC and for the binding of GlcNAc-6-P were developed [16]
The Nag regulon consists of two divergent operons, nagE and nagBACD. nagC encodes the repressor of this regulon.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
NagC Functional   Apo [BPP], [IMP] [1]
NagC-N-acetyl-D-glucosamine-6-phosphate Non-Functional Allosteric Holo [BPP], [IMP] [1]
Evolutionary Family: MarR
Sensing class: External sensing using transported metabolites
Connectivity class: Local Regulator
Gene name: nagC
  Genome position: 700374-701594
  Length: 1221 bp / 406 aa
Operon name: nagBAC-umpH
TU(s) encoding the TF:
Transcription unit        Promoter
nagBAC-umpH
nagBp
nagC
nagCp1
nagC
nagCp2


Regulon       
Regulated gene(s) chbA, chbB, chbC, chbF, chbG, chbR, chiP, creA, creB, creC, creD, crr, dinI, feoA, feoB, feoC, fimB, galP, glmS, glmU, manX, manY, manZ, nagA, nagB, nagC, nagE, nanC, nanM, nanS, ptsH, ptsI, umpH, ybfN, ydeM, ydeN, ydeP
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
carbon compounds (14)
membrane (9)
Phosphotransferase Systems (PEP-dependent PTS) (8)
amino sugar conversions (5)
operon (4)
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Regulated operon(s) chbBCARFG, chiP-ybfN, creABCD, dinI, feoABC, fimB, galP, glmUS, manXYZ, nagBAC-umpH, nagE, nanCMS, ptsHI-crr, ydeNM, ydeP
First gene in the operon(s) chbB, chiP, creA, dinI, feoA, fimB, galP, glmU, glmU, manX, nagB, nagE, nanC, nanC, ptsH, ptsH, ptsH, ydeN, ydeP
Simple and complex regulons AraC,NagC
BasR,H-NS,IHF,NagC,NanR
CRP,ChbR,NagC
CRP,Cra,Mlc,NagC
CRP,GalR,GalS,NagC
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[NagC,+](2)
[NagC,-](15)


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
  NagC repressor chbBp nd -112.0 -219.0 chbB, chbC, chbA, chbR, chbF, chbG
ggcctgagttCTTAATTATCTTCGCGAATTATTtgcccgaaat
1821827 1821849 [AIBSCS], [BPP], [GEA], [HIBSCS], [SM] [2], [3], [4]
  NagC repressor chbBp nd 1.0 -107.0 chbB, chbC, chbA, chbR, chbF, chbG
tctataccgtATACTCCTTTCAGCCACAAAAAAagtcatgttg
1821715 1821737 [BPP], [GEA], [HIBSCS] [4]
  NagC repressor chiPp nd -244.0 -342.5 chiP, ybfN
cggcgtttttTCTGCTTTTCTTCGCGAATTAATTccgcttcgca
707980 708003 [BPP], [GEA] [5]
  NagC repressor chiPp nd -22.0 -120.0 chiP, ybfN
gaaagagattGATAATTCGCGTCGCGAAAAATAgtctgttcct
708203 708225 [AIBSCS], [BPP], [GEA] [3], [5]
  NagC repressor creAp Sigma70 2.0 -43.0 creA, creB, creC, creD
taatcaatatGTTATTTACCGTGACGAACTAATtgctcgtgta
4635467 4635489 [AIBSCS] [3]
  NagC repressor dinIp Sigma70 -14.0 -36.0 dinI
ttgtcattagGTTATTTTACCTGTATAAATAACcagtatattc
1121512 1121534 [AIBSCS] [3]
  NagC unknown feoAp Sigma70 -128.0 -234.0 feoA, feoB, feoC
agccagtccgGGTAATTCACTATTCGAATTATAttttcgctgc
3539918 3539940 [AIBSCS] [3]
  NagC activator fimBp2 nd -674.0 -964.0 fimB
aaaccagattTGCAATTCGTGTCACAAAATATGtcgatctttt
4539982 4540004 [AIBSCS], [BPP], [GEA], [HIBSCS], [SM] [6], [7], [8]
  NagC activator fimBp2 nd -462.0 -752.0 fimB
tcaggctgagCATAATTCTCATCATGAAATATGtttcctggtt
4540194 4540216 [AIBSCS], [BPP], [HIBSCS], [SM] [3], [7], [8]
  NagC repressor galPp Sigma70 2.0 -28.0 galP
actcacctatCTTAATTCACAATAAAAAATAACcatattggag
3088245 3088267 [AIBSCS], [BPP], [SM] [3], [9]
  NagC activator glmUp1 Sigma70 -199.0 -222.0 glmU, glmS
ctgttttcctGTTTATTCATTGATCGAAATAAGagcaaaaaca
3915411 3915433 [BPP], [HIBSCS], [SM] [10], [11]
  NagC activator glmUp1 Sigma70 -46.0 -69.0 glmU, glmS
ttatcctctgTCCATTTCACGATGAAAAAAATGtagttttttc
3915258 3915280 [BPP], [HIBSCS], [SM] [10], [11]
  NagC repressor glmUp2 Sigma70 -96.0 -222.0 glmU, glmS
ctgttttcctGTTTATTCATTGATCGAAATAAGagcaaaaaca
3915411 3915433 [BPP], [HIBSCS], [SM] [10], [11]
  NagC repressor glmUp2 Sigma70 58.0 -69.0 glmU, glmS
ttatcctctgTCCATTTCACGATGAAAAAAATGtagttttttc
3915258 3915280 [BPP], [HIBSCS], [SM] [10], [11]
  NagC repressor manXp Sigma70 -80.0 -195.0 manX, manY, manZ
atgtgacaagGATATTTTACCTTTCGAAATTTCtgctaatcga
1901842 1901864 [AIBSCS], [BCE], [GEA], [HIBSCS] [3], [10], [12], [13]
  NagC repressor manXp Sigma70 4.0 -112.0 manX, manY, manZ
cgatatctaaAATAAATCGCGAAACGCAGGGGTttttggttgt
1901925 1901947 [BCE], [GEA] [12], [13]
  NagC repressor nagBp Sigma70 -101.0 -198.0 nagB, nagA, nagC, umpH
tgtgtgaaaaTTTAATTCGTATCGCAAATTAAAcgcgtgtctt
703798 703820 [BPP], [GEA], [SM] [10], [13], [14], [15]
  NagC repressor nagBp Sigma70 -7.0 -104.0 nagB, nagA, nagC, umpH
aaccagaaaaCTTATTTTATCATTCAAAAAATCaggtcggatt
703704 703726 [BPP], [GEA], [SM] [10], [13], [14], [15]
  NagC repressor nagEp Sigma70 -125.0 -229.0 nagE
aatccgacctGATTTTTTGAATGATAAAATAAGttttctggtt
703704 703726 [BPP], [GEA], [SM] [10], [13], [14], [15]
  NagC repressor nagEp Sigma70 -31.0 -135.0 nagE
aagacacgcgTTTAATTTGCGATACGAATTAAAttttcacaca
703798 703820 [BPP], [GEA], [SM] [10], [13], [14], [15]
  NagC repressor nanCp nd -277.0 -704.0 nanC, nanM, nanS
aaccaggaaaCATATTTCATGATGAGAATTATGctcagcctga
4540194 4540216 [AIBSCS], [BPP], [HIBSCS], [SM] [3], [7], [8]
  NagC repressor nanCp nd -65.0 -492.0 nanC, nanM, nanS
aaaagatcgaCATATTTTGTGACACGAATTGCAaatctggttt
4539982 4540004 [AIBSCS], [BPP], [GEA], [HIBSCS], [SM] [6], [7], [8]
  NagC repressor ptsHp3 nd 7.0 -251.0 ptsH, ptsI, crr
aaccagactaATTATTTTGATGCGCGAAATTAAtcgttacagg
2533502 2533524 [AIBSCS] [3]
  NagC repressor ptsHp4 Sigma70 13.0 -251.0 ptsH, ptsI, crr
aaccagactaATTATTTTGATGCGCGAAATTAAtcgttacagg
2533502 2533524 [AIBSCS] [3]
  NagC repressor ptsHp5 nd 16.0 -251.0 ptsH, ptsI, crr
aaccagactaATTATTTTGATGCGCGAAATTAAtcgttacagg
2533502 2533524 [AIBSCS] [3]
  NagC repressor ydeNp Sigma70 -140.0 -170.0 ydeN, ydeM
caataaattaGTTGTTTATCGGCGAGAAATTACttaatagaac
1582683 1582705 [AIBSCS] [3]
  NagC repressor ydeNp Sigma70 -16.0 -46.0 ydeN, ydeM
cttacatccaCTTATTTCTCTTCGTAAAATTACtttggaatta
1582559 1582581 [AIBSCS] [3]
  NagC repressor ydePp Sigma70 -28.0 -206.0 ydeP
aagccagagtCTTATTTTTTATATTGAAAAATAtgttaattta
1586681 1586703 [AIBSCS] [3]


Alignment and PSSM for NagC TFBSs    

Aligned TFBS of NagC   
  Sequence
 

Position weight matrix (PWM).   
A	6	3	16	8	1	0	0	10	0	2	12	6	4	9	8	19	20	12	2	18	9	3
C	1	2	0	0	0	0	13	0	13	4	2	5	0	9	0	1	0	0	2	0	0	7
G	2	0	0	1	0	0	0	9	0	12	2	1	9	2	8	0	0	3	2	1	3	7
T	11	15	4	11	19	20	7	1	7	2	4	8	7	0	4	0	0	5	14	1	8	3

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    

 [BPP] Binding of purified proteins

 [IMP] Inferred from mutant phenotype

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences

 [SM] Site mutation

 [BCE] Binding of cellular extracts



Reference(s)    

 [1] Plumbridge JA., 1991, Repression and induction of the nag regulon of Escherichia coli K-12: the roles of nagC and nagA in maintenance of the uninduced state., Mol Microbiol. 5(8):2053-62

 [2] Kachroo AH., Kancherla AK., Singh NS., Varshney U., Mahadevan S., 2007, Mutations that alter the regulation of the chb operon of Escherichia coli allow utilization of cellobiose., Mol Microbiol. 66(6):1382-95

 [3] Oberto J., 2010, FITBAR: a web tool for the robust prediction of prokaryotic regulons., BMC Bioinformatics. 11:554

 [4] Plumbridge J., Pellegrini O., 2004, Expression of the chitobiose operon of Escherichia coli is regulated by three transcription factors: NagC, ChbR and CAP., Mol Microbiol. 52(2):437-49

 [5] Plumbridge J., Bossi L., Oberto J., Wade JT., Figueroa-Bossi N., 2014, Interplay of transcriptional and small RNA-dependent control mechanisms regulates chitosugar uptake in Escherichia coli and Salmonella., Mol Microbiol. 92(4):648-58

 [6] Condemine G., Berrier C., Plumbridge J., Ghazi A., 2005, Function and expression of an N-acetylneuraminic acid-inducible outer membrane channel in Escherichia coli., J Bacteriol. 187(6):1959-65

 [7] Sohanpal BK., El-Labany S., Lahooti M., Plumbridge JA., Blomfield IC., 2004, Integrated regulatory responses of fimB to N-acetylneuraminic (sialic) acid and GlcNAc in Escherichia coli K-12., Proc Natl Acad Sci U S A. 101(46):16322-7

 [8] Sohanpal BK., Friar S., Roobol J., Plumbridge JA., Blomfield IC., 2007, Multiple co-regulatory elements and IHF are necessary for the control of fimB expression in response to sialic acid and N-acetylglucosamine in Escherichia coli K-12., Mol Microbiol. 63(4):1223-36

 [9] El Qaidi S., Allemand F., Oberto J., Plumbridge J., 2008, Repression of galP, the galactose transporter in Escherichia coli, requires the specific regulator of N-acetylglucosamine metabolism., Mol Microbiol

 [10] 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

 [11] Plumbridge J., 1995, Co-ordinated regulation of amino sugar biosynthesis and degradation: the NagC repressor acts as both an activator and a repressor for the transcription of the glmUS operon and requires two separated NagC binding sites., EMBO J. 14(16):3958-65

 [12] 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

 [13] Plumbridge J., Kolb A., 1991, CAP and Nag repressor binding to the regulatory regions of the nagE-B and manX genes of Escherichia coli., J Mol Biol. 217(4):661-79

 [14] Plumbridge J., Kolb A., 1993, DNA loop formation between Nag repressor molecules bound to its two operator sites is necessary for repression of the nag regulon of Escherichia coli in vivo., Mol Microbiol. 10(5):973-81

 [15] Plumbridge J., Kolb A., 1998, DNA bending and expression of the divergent nagE-B operons., Nucleic Acids Res. 26(5):1254-60

 [16] Pennetier C., Dominguez-Ramirez L., Plumbridge J., 2008, Different regions of Mlc and NagC, homologous transcriptional repressors controlling expression of the glucose and N-acetylglucosamine phosphotransferase systems in Escherichia coli, are required for inducer signal recognition., Mol Microbiol. 67(2):364-77

 [17] Plumbridge J., 2001, Regulation of PTS gene expression by the homologous transcriptional regulators, Mlc and NagC, in Escherichia coli (or how two similar repressors can behave differently)., J Mol Microbiol Biotechnol. 3(3):371-80

 [18] Titgemeyer F., Reizer J., Reizer A., Saier MH., 1994, Evolutionary relationships between sugar kinases and transcriptional repressors in bacteria., Microbiology. 140 ( Pt 9):2349-54

 [19] Hansen T., Reichstein B., Schmid R., Schonheit P., 2002, The first archaeal ATP-dependent glucokinase, from the hyperthermophilic crenarchaeon Aeropyrum pernix, represents a monomeric, extremely thermophilic ROK glucokinase with broad hexose specificity., J Bacteriol. 184(21):5955-65

 [20] 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



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