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NadR DNA-binding transcriptional repressor

Synonyms: NadR
Summary:
The multifunctional protein NadR has enzymatic as well as regulatory activity. Initially thought to only function as a transcriptional regulator that represses genes involved in transport and de novo synthesis of NAD [2, 3], NadR was later shown to have nicotinamide mononucleotide (NMN) adenylyltransferase activity [5] and predicted to have ribosylnicotinamide kinase activity [1]. NadR is composed of three different domains: an N-terminal helix-turn-helix domain for DNA binding, a central NMN adenylyltransferase domain that contains an ATP-binding site, and a C-terminal ribosylnicotinamide kinase domain [1]. NadR is often found to be mutated in long-term evolution experiments; interestingly, mutations are usually only found in the N- and C-terminal domains []. It has been proposed that NadR recognizes and binds to two palindromic sequences of 6 bp separated by six less conserved nucleotides.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
NadR Functional   [AIFS], [IMP] [1], [2]
Evolutionary Family: HTH_3
Connectivity class: Local Regulator
Gene name: nadR
  Genome position: 4627315-4628547
  Length: 1233 bp / 410 aa
Operon name: serB-radA-nadR
TU(s) encoding the TF:
Transcription unit        Promoter
 
 


Regulon       
Regulated gene(s) nadA, nadB, pncB, pnuC
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
nicotinamide adenine dinucleotide (3)
nucleotide and nucleoside conversions (1)
Transporters of Unknown Classification (1)
membrane (1)
Regulated operon(s) nadA-pnuC, nadB, pncB
First gene in the operon(s) nadB, pncB, nadA
Simple and complex regulons CRP,NadR
NadR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[NadR,-](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 (Confirmed, Strong, Weak) References
  NadR repressor nadAp nd -57.5 -81.5 nadA, pnuC
tcgactatctTGTTTAGCATATAAAACAaattacaccg
 781995 782012 [ICWHO], [IMP] [2], [3]
  NadR repressor nadBp Sigma70 48.5 -15.5 nadB
gaccaaaccaTGTTTAGTAAATTAAACAaagaaaatga
 2710396 2710413 [AIBSCS], [BPP], [CV(GEA)], [CV(GEA)], [GEA], [IMP] [2], [3], [4], [5]
  NadR repressor pncBp Sigma70 20.5 -38.5 pncB
ttcctgaagaTGTTTATTGTACTAAACGctcctgtacg
 990386 990403 [AIBSCS] [3], [4]


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


Evidence    

 [AIFS] Automated inference of function from sequence

 [IMP] Inferred from mutant phenotype

 [ICWHO] Inferred computationally without human oversight

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [BPP] Binding of purified proteins

 [CV(GEA)] cross validation(GEA)

 [GEA] Gene expression analysis


Reference(s)    

 [1] Kurnasov OV., Polanuyer BM., Ananta S., Sloutsky R., Tam A., Gerdes SY., Osterman AL., 2002, Ribosylnicotinamide kinase domain of NadR protein: identification and implications in NAD biosynthesis., J Bacteriol 184(24):6906-17

 [2] Tritz GJ., Chandler JL., 1973, Recognition of a gene involved in the regulation of nicotinamide adenine dinucleotide biosynthesis., J Bacteriol 114(1):128-36

 [3] Gerasimova AV., Gelfand MS., 2005, Evolution of the NadR regulon in Enterobacteriaceae., J Bioinform Comput Biol 3(4):1007-19

 [4] 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

 [5] Raffaelli N., Lorenzi T., Mariani PL., Emanuelli M., Amici A., Ruggieri S., Magni G., 1999, The Escherichia coli NadR regulator is endowed with nicotinamide mononucleotide adenylyltransferase activity., J Bacteriol 181(17):5509-11


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