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HipB DNA-binding transcriptional repressor

Synonyms: HipB
Summary:
HipB is a transcriptional repressor that functions as the antagonist of HipA, which was the first protein found to mediate the phenomenon of persistence in E. coli. A small fraction of cells within a population are dormant persister cells; these cells are phenotypic variants that are not killed by antibiotics, leading to multidrug tolerance (MDT). Persistence may be ultimately due to global remodeling of the persister cell's ribosomes |CITS: [25425348]|. The HipAB system can be categorized as a type II toxin/antitoxin module.
In the absence of its binding partner HipB, HipA is toxic to the cell |CITS: [1715862][8021189][20616060]|. Above a certain threshold, the level of HipA in the cell determines the typical duration of growth arrest. The threshold level is determined by the level of HipB |CITS: [20616060]|. The HipAB system appears to be regulated at the level of HipB stability. Degradation of HipB is mainly dependent on the Lon protease, and is dependent on an unstructured 16 amino acid domain at the C terminus of the protein |CITS: [22720069]|.
A variety of crystal structures of HipB in complexes with DNA and HipA have been solved |CITS: [19150849][19622872][22999936][26222023]|. Binding to HipB may lock HipA into a catalytically inactive conformation |CITS: [19150849]|. The crystal structure of an extended promoter region that contained two operator sites revealed that the interaction with HipB dimers bound to both sites leads to dimerizarion of HipA, which blocks the active sites of both HipA molecules |CITS: [26222023]|.
The HipA-mediated phenotypic switch has been investigated at the single cell level |CITS: [15308767]|, and mathematical models have been developed |CITS: [18721814][22607777]|, suggesting that phenotypic variation in persister levels within a population can be due to different levels of noise in the regulation of the gene circuit |CITS: [22607777]|.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
HipB     nd nd
Evolutionary Family: HTH_3
Connectivity class: Local Regulator
Gene name: hipB
  Genome position: 1592176-1592442
  Length: 267 bp / 88 aa
Operon name: hipBA
TU(s) encoding the TF:
Transcription unit        Promoter
hipBA
hipBp


Regulon       
Regulated gene(s) fadH, hipA, hipB, mazE, mazF, relA
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
translation (2)
defense/survival (2)
starvation (2)
other (mechanical, nutritional, oxidative stress) (2)
cell killing (2)
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Regulated operon(s) fadH, hipBA, relA-mazEFG
First gene in the operon(s) fadH, hipB, relA
Simple and complex regulons ArcA,CRP,FadR,HipB
HipAB,HipB
HipAB,HipB,IHF
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[HipB,-](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
  HipB repressor fadHp nd -132.5 -173.5 fadH
gtggacgcctTATCCGCCCTACATGTGCAATTCCGTAACCTGGATAaaacgcgaca
3231474 3231509 [BPP], [GEA], [HIBSCS] [1]
  HipB repressor hipBp Sigma70 -85.5 -125.5 hipB, hipA
atcctcctttTTATCCGCGATCGCGGATATcgcagcgttt
1592558 1592577 [BPP], [GEA], [HIBSCS] [2]
  HipB repressor hipBp Sigma70 -57.5 -97.5 hipB, hipA
atcgcagcgtTTATCCCGTAGAGCGGATAAgatgtgtttc
1592530 1592549 [BPP], [GEA], [HIBSCS] [2]
  HipB repressor hipBp Sigma70 -18.5 -58.5 hipB, hipA
ccagattgacTTATCCTCACTAAAGGATAAaacttataat
1592491 1592510 [BPP], [GEA], [HIBSCS] [2]
  HipB repressor hipBp Sigma70 10.5 -30.5 hipB, hipA
aaaacttataATATCCCCTTAAGCGGATAAacttgctgtg
1592463 1592482 [BPP], [GEA], [HIBSCS] [2]
  HipB repressor relAp1 Sigma70 5.0 -174.0 relA, mazE, mazF
atagtttatgTATCCTGTAACCCTGCAACGCTGGCTCGGGATAgcgaagcgtt
2913809 2913841 [AIBSCS], [BPP], [GEA] [1]


Alignment and PSSM for HipB TFBSs    

Aligned TFBS of HipB   
  Sequence
 

Position weight matrix (PWM).   
A	2	0	3	2	2	3	0	4	0	0	2	1	1	1	1	1	4	1	1	0	0	4	0	5	5	5	4	1	0	0
C	1	2	0	1	3	1	1	0	0	6	4	2	5	0	3	0	1	1	3	0	2	0	0	0	0	0	2	1	2	1
G	1	0	3	1	1	0	0	0	2	0	0	2	0	2	1	0	1	4	2	5	4	2	2	1	0	0	0	3	2	3
T	2	4	0	2	0	2	5	2	4	0	0	1	0	3	1	5	0	0	0	1	0	0	4	0	1	1	0	1	2	2

PWM logo   


 


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


Evidence    

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences

 [AIBSCS] Automated inference based on similarity to consensus sequences



Reference(s)    

 [1] Lin CY., Awano N., Masuda H., Park JH., Inouye M., 2013, Transcriptional Repressor HipB Regulates the Multiple Promoters in Escherichia coli., J Mol Microbiol Biotechnol. 23(6):440-447

 [2] Black DS., Irwin B., Moyed HS., 1994, Autoregulation of hip, an operon that affects lethality due to inhibition of peptidoglycan or DNA synthesis., J Bacteriol. 176(13):4081-91



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