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ZraR DNA-binding transcriptional activator

Synonyms: ZraR, ZraR-Phosphorylated
ZraR, "zinc resistance-associated regulator," controls the expression of genes involved in tolerance to high zinc concentrations. Based on chromatin immunoprecipitation followed by sequencing (ChIp-Seq) and RT-qPCR, 25 new genes regulated by ZraR were identified. The genes encode proteins of diverse functions that may be critical to maintain envelope integrity and cell survival under stressful conditions; they are mostly involved in the response against stress [2]. The genes of the ZraR regulon are also involved in replication and protein synthesis [2]. This regulator is a member of the two-component regulatory system ZraS/ZraR. The operon contains both genes zraR, which encodes the response regulator, and zraS, which encodes the sensor kinase, and 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 [1]. ZraS and ZraR show considerable homology with the proteins NtrB and NtrC, respectively [3].
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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 nd nd
ZraR-Phosphorylated Functional Covalent Holo [APPHINH], [GEA], [HIFS], [ICA], [IEP], [IFC] [1], [2]
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)
osmotic pressure (1)
pH (1)
protection (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 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
  ZraR-Phosphorylated activator zraPp Sigma54 -107.0 -131.0 zraP
4201811 4201827 [BPP], [GEA] [1]
  ZraR-Phosphorylated activator zraPp Sigma54 -78.0 -102.0 zraP
4201782 4201798 [APIORCISFBSCS], [BPP], [CV(GEA)], [CV(GEA)], [GEA] [1]
  ZraR-Phosphorylated activator zraSp Sigma54 -115.0 -136.0 zraS, zraR
4201782 4201798 [APIORCISFBSCS], [BPP], [CV(GEA)], [CV(GEA)], [GEA] [1]
  ZraR-Phosphorylated activator zraSp Sigma54 -86.0 -107.0 zraS, zraR
4201811 4201827 [BPP], [GEA] [1]

High-throughput Transcription factor binding sites (TFBSs)

  Functional conformation Function Object name Object type Distance to first Gene Sequence LeftPos RightPos Center Position Growth Condition Evidence (Confirmed, Strong, Weak) References
  ZraR-Phosphorylated activator cspB tu nd
1641644 1641662 1641652.5 nd , [ICWHO], [IEP] [2]
  ZraR-Phosphorylated activator nd tu nd
4640231 4640249 4640239.5 nd , [ICWHO], [IEP] [2]
  ZraR-Phosphorylated activator yrdD-rimN-aroE-yrdB tu nd
3431988 3432006 3431996.5 nd , [ICWHO], [IEP] [2]

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


 [APPHINH] Assay of protein purified to homogeneity from its native host

 [GEA] Gene expression analysis

 [HIFS] Human inference of function from sequence

 [ICA] Inferred by computational analysis

 [IEP] Inferred from expression pattern

 [IFC] Inferred by functional complementation

 [BPP] Binding of purified proteins

 [APIORCISFBSCS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [CV(GEA)] cross validation(GEA)

 [CE] ChIP-seq evidence

 [ICWHO] Inferred computationally without human oversight


 [1] 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

 [2] Rome K., Borde C., Taher R., Cayron J., Lesterlin C., Gueguen E., De Rosny E., Rodrigue A., 2018, The Two-Component System ZraPSR Is a Novel ESR that Contributes to Intrinsic Antibiotic Tolerance in Escherichia coli., J Mol Biol 430(24):4971-4985

 [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