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NanR DNA-binding transcriptional dual regulator

Synonyms: NanR-N-acetylneuraminate, NanR
Summary:
The genes regulated by NanR, "N-acetyl-neuraminic acid regulator," are involved in N-acetyl-neuraminic acid (or sialic acid) transport and metabolism [7] and in OFF/ON switching of type 1 fimbriation. N-acetylneuraminate (Neu5Ac), which is the most common sialic acid, induces the catabolism of sialic acids operons by directly inactivating NanR [1], converting the predominantly dimeric form of the repressor to an inactive monomer [4]. NanR is a member of the FadR/GntR family. Members of this family have two domains, an N-terminal domain with a helix-turn-helix DNA-binding motif and a C-terminal domain with dimerization and effector-binding motifs. Three-dimensional models of the N terminus of FadR and NanR show topological similarities and a ~26% sequence identity between them [7]. The NanR dimer regulates transcription when it binds, in an asymmetric manner, to a region of ~30 bp that contains a set of conserved operators with two or three exact, or nearly exact, repeats of the hexanucleotide sequence GGTATA; this binding occurs in a cooperative way and is mediated by an N-terminal extension of 32 residues in NanR [4, 9] However, this protein can be displaced from this region byN-acetyl-neuraminic acid (Neu5Ac), which causes a conformational change in the protein [9] One dimer of NarR binding to a molecule of Neu5Ac causes alteration of the DNA binding activity of the protein but not its oligomeric state [9] When this protein is repressing transcription, it overlaps the whole promoter region [1, 7].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
NanR Functional   Apo [BPP] [1]
NanR-N-acetylneuraminate Non-Functional Allosteric Holo [BPP] [1]
Evolutionary Family: GntR
Sensing class: External sensing using transported metabolites
Connectivity class: Local Regulator
Gene name: nanR
  Genome position: 3373698-3374489
  Length: 792 bp / 263 aa
Operon name: nanR
TU(s) encoding the TF:
Transcription unit        Promoter
nanR
 


Regulon       
Regulated gene(s) fimB, nanA, nanC, nanE, nanK, nanM, nanQ, nanS, nanT, nanX, nanY
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
amino sugar conversions (4)
carbon compounds (3)
Porters (Uni-, Sym- and Antiporters) (2)
membrane (2)
fimbri, pili (1)
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Regulated operon(s) fimB, nanATEKQ, nanCMS, nanXY
First gene in the operon(s) fimB, nanA, nanC, nanX
Simple and complex regulons BasR,DksA,DksA-ppGpp,H-NS,IHF,NagC,NanR,ppGpp
CRP,Fis,NanR
CRP,NagC,NanR
NanR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[NanR,-](3)
[NanR,+](1)


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
  NanR activator fimBp2 nd -744.5 -1034.5 fimB 4539922 4539923 [GEA], [APIORCISFBSCS], [BPP], [GS], [SM] [1], [2], [3], [4], [5], [6]
  NanR activator fimBp2 nd -736.5 -1026.5 fimB 4539930 4539931 [GEA], [APIORCISFBSCS], [BPP], [GS], [SM] [1], [2], [3], [4], [5], [6]
  NanR activator fimBp2 nd -727.5 -1017.5 fimB 4539939 4539940 [GEA], [APIORCISFBSCS], [BPP], [GS], [SM] [1], [2], [3], [4], [5], [6]
  NanR repressor nanAp Sigma70 -11.5 -55.5 nanA, nanT, nanE, nanK, nanQ 3373631 3373632 [GEA], [BPP], [SM] [4], [7], [8]
  NanR repressor nanAp Sigma70 -2.5 -46.5 nanA, nanT, nanE, nanK, nanQ 3373622 3373623 [GEA], [BPP], [SM] [4], [7], [8]
  NanR repressor nanAp Sigma70 6.5 -38.5 nanA, nanT, nanE, nanK, nanQ 3373614 3373615 [GEA], [BPP], [SM] [4], [7], [8]
  NanR repressor nanCp nd -11.5 -438.5 nanC, nanM, nanS 4539939 4539940 [GEA], [APIORCISFBSCS], [BPP], [GS], [SM] [2], [3], [4], [5]
  NanR repressor nanCp nd -2.5 -429.5 nanC, nanM, nanS 4539930 4539931 [GEA], [APIORCISFBSCS], [BPP], [GS], [SM] [2], [3], [4], [5]
  NanR repressor nanCp nd 6.5 -421.5 nanC, nanM, nanS 4539922 4539923 [GEA], [APIORCISFBSCS], [BPP], [GS], [SM] [2], [3], [4], [5]
  NanR repressor yjhBp2 Sigma32 -393.5 -431.5 nanX, nanY 4503626 4503627 [GEA], [BPP], [SM] [4]
  NanR repressor yjhBp2 Sigma32 -384.5 -422.5 nanX, nanY 4503635 4503636 [GEA], [BPP], [SM] [4]
  NanR repressor yjhBp2 Sigma32 -376.5 -414.5 nanX, nanY 4503643 4503644 [GEA], [BPP], [SM] [4]


Alignment and PSSM for NanR TFBSs    

Aligned TFBS of NanR   
  Sequence
  TATACCT
  TATACCT
  TATACCT
  TATACCT
  TATACCT
  TATACCA
  TATACCA
  TATACCA
  TGCACCT

Position weight matrix (PWM). NanR matrix-quality result   
A	0	8	0	9	0	0	3
C	0	0	1	0	9	9	0
G	0	1	0	0	0	0	0
T	9	0	8	0	0	0	6

Consensus   
;	consensus.strict             	TATACCt
;	consensus.strict.rc          	AGGTATA
;	consensus.IUPAC              	TATACCw
;	consensus.IUPAC.rc           	WGGTATA
;	consensus.regexp             	TATACC[at]
;	consensus.regexp.rc          	[AT]GGTATA

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




Reference(s)    

 [1] 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

 [2] 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

 [3] El-Labany S., Sohanpal BK., Lahooti M., Akerman R., Blomfield IC., 2003, Distant cis-active sequences and sialic acid control the expression of fimB in Escherichia coli K-12., Mol Microbiol 49(4):1109-18

 [4] Kalivoda KA., Steenbergen SM., Vimr ER., 2013, Control of the Escherichia coli sialoregulon by transcriptional repressor NanR., J Bacteriol 195(20):4689-701

 [5] Shimada T., Ogasawara H., Ishihama A., 2018, Single-target regulators form a minor group of transcription factors in Escherichia coli K-12., Nucleic Acids Res 46(8):3921-3936

 [6] 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

 [7] Kalivoda KA., Steenbergen SM., Vimr ER., Plumbridge J., 2003, Regulation of sialic acid catabolism by the DNA binding protein NanR in Escherichia coli., J Bacteriol 185(16):4806-15

 [8] Plumbridge J., Vimr E., 1999, Convergent pathways for utilization of the amino sugars N-acetylglucosamine, N-acetylmannosamine, and N-acetylneuraminic acid by Escherichia coli., J Bacteriol 181(1):47-54

 [9] Horne CR., Venugopal H., Panjikar S., Wood DM., Henrickson A., Brookes E., North RA., Murphy JM., Friemann R., Griffin MDW., Ramm G., Demeler B., Dobson RCJ., 2021, Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism., Nat Commun 12(1):1988

 [10] Chu D, Roobol J, Blomfield IC, 2008, A theoretical interpretation of the transient sialic acid toxicity of a nanR mutant of Escherichia coli., J Mol Biol, 375(3):875 10.1016/j.jmb.2007.10.073

 [11] Oshima T, Wada C, Kawagoe Y, Ara T, Maeda M, Masuda Y, Hiraga S, Mori H, 2002, Genome-wide analysis of deoxyadenosine methyltransferase-mediated control of gene expression in Escherichia coli., Mol Microbiol, 45(3):673 10.1046/j.1365-2958.2002.03037.x



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