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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 |CITS: [4349027][16078372]|, NadR was later shown to have nicotinamide mononucleotide (NMN) adenylyltransferase activity |CITS: [10464228]| and predicted to have ribosylnicotinamide kinase activity |CITS: [12446641]|.
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 |CITS: [12446641]|. 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 |CITS: [18029306]|.
It has been proposed that NadR recognizes and binds to two palindromic sequences of 6 bp separated by six less conserved nucleotides. This site is conserved in some NadR ortholog target genes in some enterobacteria, and it was also identified upstream of the nadR gene itself in E. carotovora, S. marcescens, Y. pestis, and Y. enterocolitica , but not in Escherichia coli |CITS: [16078372]|.
Review: |CITS: [18086213]|


Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
NadR     nd nd
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
radA-nadR
null


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) nadA, nadB, pncB
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 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 nd nd nadA, pnuC nd nd [ICWHO], [IMP] [1], [2]
  NadR repressor nadBp Sigma70 nd nd nadB nd nd [AIBSCS], [BPP], [GEA], [IMP] [1], [2], [3], [4]
  NadR repressor pncBp Sigma70 nd nd pncB nd nd [AIBSCS] [1], [3]


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


Evidence    

 [ICWHO] Inferred computationally without human oversight

 [IMP] Inferred from mutant phenotype

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis



Reference(s)    

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

 [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] 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

 [4] 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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