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ZraR DNA-binding transcriptional activator

Synonyms: ZraR-Phosphorylated, ZraR
ZraR, zinc resistance-associated regulator, controls the expression of genes involved in tolerance to high zinc concentrations. ZraR recognizes a DNA sequence of two inverted repeats of 17 bp separated by 12 bp [2].
This regulator is a member of the two-component regulatory system ZraS/ZraR. The operon containing both genes zraR, encoding the response regulator, and zraS, encoding the sensor kinase, is located next to and in the opposite direction to zraP, a gene regulated by ZraR. It has been suggested that ZraS functions as a zinc receptor [2]. ZraS and ZraR show considerable homology with the proteins NtrB and NtrC, respectively [3].
ZraR also belongs to the group of σ54-dependent transcriptional regulators [2]. Members of this group contain three domains: the sensory domain located in the N terminus, the central domain involved in ATP hydrolysis and interaction with σ54, and the C-terminal domain, which contains a helix-turn-helix motif [1, 3].
A regulatory role related to the activity of the enzyme hydrogenase 3 has been assigned to ZraR (previously called HydG) [3], but it was demonstrated that this regulation was nonspecific [2].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
ZraR Non-Functional   Apo [IPI] [1]
ZraR-Phosphorylated Functional Covalent Holo [IPI] [1]
Evolutionary Family: EBP
Sensing class: External-Two-component systems
Connectivity class: Local Regulator
Gene name: zraR
  Genome position: 4203320-4204645
  Length: 1326 bp / 441 aa
Operon name: zraSR
TU(s) encoding the TF:
Transcription unit        Promoter

Regulated gene(s) zraP, zraR, zraS
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
fermentation (2)
two component regulatory systems (external signal) (2)
Putative uncharacterized transport protein (1)
other (mechanical, nutritional, oxidative stress) (1)
Transcription related (1)
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Regulated operon(s) zraP, zraSR
First gene in the operon(s) zraP, zraS
Simple and complex regulons CRP,ZraR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

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
  ZraR-Phosphorylated activator zraPp Sigma54 -107.0 -131.0 zraP
4201811 4201827 [BPP], [GEA] [2]
  ZraR-Phosphorylated activator zraPp Sigma54 -78.0 -102.0 zraP
4201782 4201798 [BPP], [GEA], [HIBSCS] [2]
  ZraR-Phosphorylated activator zraSp Sigma54 -115.0 -136.0 zraS, zraR
4201782 4201798 [BPP], [GEA], [HIBSCS] [2]
  ZraR-Phosphorylated activator zraSp Sigma54 -86.0 -107.0 zraS, zraR
4201811 4201827 [BPP], [GEA] [2]

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


 [IPI] Inferred from physical interaction

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences


 [1] Sallai L., Tucker PA., 2005, Crystal structure of the central and C-terminal domain of the sigma(54)-activator ZraR., J Struct Biol. 151(2):160-70

 [2] Leonhartsberger S., Huber A., Lottspeich F., Bock A., 2001, The hydH/G Genes from Escherichia coli code for a zinc and lead responsive two-component regulatory system., J Mol Biol. 307(1):93-105

 [3] Stoker K., Reijnders WN., Oltmann LF., Stouthamer AH., 1989, Initial cloning and sequencing of hydHG, an operon homologous to ntrBC and regulating the labile hydrogenase activity in Escherichia coli K-12., J Bacteriol. 171(8):4448-56

 [4] Lee LJ., Barrett JA., Poole RK., 2005, Genome-wide transcriptional response of chemostat-cultured Escherichia coli to zinc., J Bacteriol. 187(3):1124-34

 [5] Mendez-Ortiz MM., Hyodo M., Hayakawa Y., Membrillo-Hernandez J., 2006, Genome-wide transcriptional profile of Escherichia coli in response to high levels of the second messenger 3',5'-cyclic diguanylic acid., J Biol Chem. 281(12):8090-9