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ZraR DNA-binding transcriptional activator

Synonyms: ZraR, ZraR-phosphorylated
Summary:
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].The protein ZraR also appears to be involved in palladium ion reduction [5]. On the other hand, based on Genomic SELEX screening it was reported that ZraR only binds strongly in the intergenic region of divergent genes zraP and zraSR operons and that with minor strength ZraR binds in the intergenic region of the divergent genes relB/ydfV and mltB/selA and close to the gene potF [6].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
ZraR Non-Functional   Apo nd nd nd
ZraR-phosphorylated Functional Covalent Holo nd nd nd
Evolutionary Family: EBP
TFBs length: 17
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
zraSR
zraSp


Regulon       
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
ZraR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[ZraR,+](2)


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 Confidence level (C: Confirmed, S: Strong, W: Weak) References
  ZraR-phosphorylated activator zraPp Sigma54 -107.0 -131.0 zraP
aagtttcaatGAGTAAAAATGACTCGCtacccgcagc
 4201811 4201827 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-CHIP-SEQ-MANUAL], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3]
  ZraR-phosphorylated activator zraPp Sigma54 -78.0 -102.0 zraP
cccgcagcagGCGAGTCATTTTTACTCgtttatcatg
 4201782 4201798 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-CHIP-EXO], [EXP-CHIP-SEQ-MANUAL], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [4]
  ZraR-phosphorylated activator zraSp Sigma54 -115.0 -136.0 zraS, zraR
catgataaacGAGTAAAAATGACTCGCctgctgcggg
 4201782 4201798 [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-CHIP-EXO], [EXP-CHIP-SEQ-MANUAL], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [3], [4]
  ZraR-phosphorylated activator zraSp Sigma54 -86.0 -107.0 zraS, zraR
gctgcgggtaGCGAGTCATTTTTACTCattgaaactt
 4201811 4201827 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-CHIP-SEQ-MANUAL], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [3]



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 Confidence level (C: Confirmed, S: Strong, W: Weak) References
  ZraR-phosphorylated activator yrdD Gene nd
attaaagaaaTGATTAATGCAGCATACCTtcattcactt
3431988 3432006 3431996.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator sspA Gene nd
aggtatagtcAGAATTTTTACTGCTACCAgccaccaggt
3377441 3377459 3377449.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator fliA Gene nd
taaacagcccTGCGTTATATGAGTTATCGgcatgattat
2001802 2001820 2001810.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator gadW Gene nd
tatttcatacTGCGATTATTTCAATTTCAgtatactaat
3664641 3664659 3664649.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator rfaD Gene nd
attcgtgtctGAGATTGTCTCTGACTCCAtaattcgaag
3793949 3793967 3793957.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator cspB Gene nd
aaagaaggaaTAAGTGAATAACACCTGAAatgagaactg
1641644 1641662 1641652.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator cpxP Gene nd
catgtttgcaGCCTGAATCGTAAACTCTCtatcgttgaa
4105762 4105780 4105770.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator exuR Gene nd
cattaacgttTCGTGTAAGTTTTAGTTTCccttcaaagc
3246527 3246545 3246535.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator yhdW Gene nd
ccagcgtgctGCTTGCCGTTGCAAATCAGgcgctgctgg
3419086 3419104 3419094.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator ssrA Gene nd
ctctccggcgGCGCGAATGAACATCTTATtggctatcac
2755430 2755448 2755438.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator acrE Gene nd
ctctttcaacCCGCGTCAAAATAAAACAGtagaatatta
3413672 3413690 3413680.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator yhhY Gene nd
cttcctgatcGCGAGACAATAATAATCATtctcattcgc
3581015 3581033 3581023.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-EXO], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator raiA Gene nd
gagatattccTCAAGTAAAAAAACATCTCttcctgcgat
2737006 2737024 2737014.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator glnA Gene nd
gcgaaatctgTGCCAACTTTTAAATTGCCcctaaaaggc
4058129 4058147 4058137.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator glnH Gene nd
tgcaactcctTGATTTTTCGAGATGCGGCaaaaacgtga
848089 848107 848097.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator yjjY Gene nd
tcatagccttCCGCTTCGAAAATACTTTTcaacgtgttg
4640231 4640249 4640239.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator rpoH Gene nd
aatgcaagctTGTGAATAAATTACGCACAaaatgtgaca
3600914 3600932 3600922.5 nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF], [EXP-CHIP-SEQ-MANUAL] S [2]
  ZraR-phosphorylated activator mdtL Gene nd
nd
nd nd nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-CHIP-SEQ-MANUAL] W [2]
  ZraR-phosphorylated activator pnp Gene nd
nd
nd nd nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-CHIP-SEQ-MANUAL] W [2]
  ZraR-phosphorylated activator tnaAB Transcription-Unit nd
nd
nd nd nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-CHIP-SEQ-MANUAL] W [2]


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


Evidence    

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [EXP-CHIP-SEQ-MANUAL] ChIP-seq evidence used in manual assertion

 [EXP-DAP-SEQ] high throughput DNA Affinity Purification (DAP) Sequencing

 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] Binding of purified proteins

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [EXP-CHIP-EXO] high throughput ChIP-exo evidence

 [COMP-AINF] Inferred computationally without human oversight


Reference(s)    

 [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] Baumgart LA, Lee JE, Salamov A, Dilworth DJ, Na H, Mingay M, Blow MJ, Zhang Y, Yoshinaga Y, Daum CG, O'Malley RC, 2021, Persistence and plasticity in bacterial gene regulation., Nat Methods, 18(12):1499 10.1038/s41592-021-01312-2

 [4] Choudhary KS, Kleinmanns JA, Decker K, Sastry AV, Gao Y, Szubin R, Seif Y, Palsson BO, 2020, Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships., mSystems, 5(6):None 10.1128/mSystems.00980-20

 [5] Matsumoto T, Kamino M, Yamada R, Konishi Y, Ogino H, 2020, Identification of genes responsible for reducing palladium ion in Escherichia coli., J Biotechnol, 324(None):7 10.1016/j.jbiotec.2020.09.015

 [6] Shimada T., Ogasawara H., Kobayashi I., Kobayashi N., Ishihama A., 2021, Single-Target Regulators Constitute the Minority Group of Transcription Factors in Escherichia coli K-12., Front Microbiol 12:697803

 [7] 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

 [8] 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 10.1016/j.jsb.2005.05.006

 [9] Naughtin M, Haftek-Terreau Z, Xavier J, Meyer S, Silvain M, Jaszczyszyn Y, Levy N, Miele V, Benleulmi MS, Ruff M, Parissi V, Vaillant C, Lavigne M, 2015, DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity., PLoS One, 10(6):e0129427 10.1371/journal.pone.0129427

 [10] Sevier SA, Levine H, 2018, Properties of gene expression and chromatin structure with mechanically regulated elongation., Nucleic Acids Res, 46(12):5924 10.1093/nar/gky382

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

 [12] 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


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