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AcrR DNA-binding transcriptional repressor

Synonyms: AcrR-ethidium, AcrR, AcrR-Proflavin, AcrR-R6G
Summary:
The "acriflavine resistance regulator," AcrR, regulates the expression of genes involved in multidrug transport and is classified in the nodulation-resistance division family [3]. It also acts as a global repressor for the mar-sox-rob regulon [2]. The crystal structure of AcrR shows that this protein is folded into nine α-helices distributed in two domains: the DNA-binding domain, which forms the typical helix-turn-helix in the N-terminal domain, and the ligand-binding domain, which forms a large internal cavity for multidrug binding in the C-terminal domain [6]. Mutational analyses have been used to identify the critical role of some amino acids for AcrR activity, such as Glu-67 [6] and Arg-45 [7]. The activity of AcrR, which belongs to the TetR family, appears to be regulated by ligands such as rhodamine 6G, ethidium, and proflavin [1].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
AcrR Functional   Apo [BPP], [IPI] [1]
AcrR-Proflavin Non-Functional Allosteric Holo [BPP], [IPI] [1]
AcrR-R6G Non-Functional Allosteric Holo [BPP], [IPI] [1]
AcrR-ethidium Non-Functional Allosteric Holo [BPP], [IPI] [1]
Evolutionary Family: TetR/AcrR
Connectivity class: Local Regulator
Gene name: acrR
  Genome position: 485761-486408
  Length: 648 bp / 215 aa
Operon name: acrR
TU(s) encoding the TF:
Transcription unit        Promoter
acrR
acrRp


Regulon       
Regulated gene(s) acrA, acrB, acrR, flhC, flhD, marA, marB, marR, micF, soxR, soxS
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
drug resistance/sensitivity (7)
Transcription related (7)
repressor (7)
operon (6)
activator (5)
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Regulated operon(s) acrAB, acrR, flhDC, marRAB, micF, soxR, soxS
First gene in the operon(s) acrA, acrR, flhD, marR, micF, soxR, soxS
Simple and complex regulons AcrR
AcrR,CRP,CpxR,Cra,Fis,MarA,MarR,Rob,SoxS
AcrR,CRP,FliZ,Fur,H-NS,HdfR,IHF,LrhA,MatA,OmpR,QseB,RcsAB,YjjQ
AcrR,EnvR,MarA,MprA,PhoP,Rob,SoxS
AcrR,FNR,Fur,SoxR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[AcrR,-](8)


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
  AcrR repressor acrAp Sigma70 -22.5 -101.5 acrA, acrB
gcgttagattTACATACATTTGTGAATGTATGTAccatagcacg
 485709 485732 [GEA], [AIBSCS], [BPP] [1], [2], [3]
  AcrR repressor acrRp Sigma70 22.5 -40.5 acrR
cgtgctatggTACATACATTCACAAATGTATGTAaatctaacgc
 485709 485732 [AIBSCS], [APIORCISFBSCS], [BCE], [BPP], [GEA], [AIBSCS], [BPP] [1], [2], [3], [4]
  AcrR repressor flhDp Sigma70 -31.5 -229.5 flhD, flhC
agcccccctcCGTTGTATGTGcgtgtagtga
 1978422 1978432 [GEA], [APIORCISFBSCS] [5]
  AcrR repressor marRp Sigma70 -40.5 -67.5 marR, marA, marB
catcggtcaaTTCATTCATTTgacttatact
 1619048 1619058 [GEA], [APIORCISFBSCS], [BPP] [2]
  AcrR repressor micFp1 Sigma70 41.0 41.0 micF
atttattaccGTCATTCATTTCTGAATGTCTGTTtacccctatt
 2313112 2313135 [AIBSCS] [4]
  AcrR repressor micFp2 Sigma38 41.0 41.0 micF
atttattaccGTCATTCATTTCTGAATGTCTGTTtacccctatt
 2313112 2313135 [AIBSCS] [4]
  AcrR repressor soxRp Sigma70 2.5 -20.5 soxR
ataattcctcAAGTTAACTTGaggtaaagcg
 4277444 4277454 [GEA], [APIORCISFBSCS], [BPP] [2]
  AcrR repressor soxSp Sigma70 -25.5 -65.5 soxS
cgctttacctCAAGTTAACTTgaggaattat
 4277444 4277454 [APIORCISFBSCS], [BPP], [GEA], [APIORCISFBSCS], [BPP] [2]


Alignment and PSSM for AcrR TFBSs    

Aligned TFBS of AcrR   
  Sequence
  TACATACATTTGTG
  TTCATTCATTTGAC
  GTCATTCATTTCTG
  CACATACAACGGAG
  CAAGTTAACTTGAG

Position weight matrix (PWM). AcrR matrix-quality result    
A	0	3	1	4	0	2	1	5	1	0	0	0	3	0
C	2	0	4	0	0	0	4	0	1	1	0	1	0	1
G	1	0	0	1	0	0	0	0	0	0	1	4	0	4
T	2	2	0	0	5	3	0	0	3	4	4	0	2	0

Consensus    
;	consensus.strict             	caCaTtCAtttGaG
;	consensus.strict.rc          	CTCAAATGAATGTG
;	consensus.IUPAC              	ywCaTwCAtttGwG
;	consensus.IUPAC.rc           	CWCAAATGWATGWR
;	consensus.regexp             	[ct][at]CaT[at]CAtttG[at]G
;	consensus.regexp.rc          	C[AT]CAAATG[AT]ATG[AT][AG]

PWM logo   


 


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


Evidence    

 [BPP] Binding of purified proteins

 [IPI] Inferred from physical interaction

 [GEA] Gene expression analysis

 [AIBSCS] Automated inference based on similarity to consensus sequences

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

 [BCE] Binding of cellular extracts


Reference(s)    

 [1] Su CC., Rutherford DJ., Yu EW., 2007, Characterization of the multidrug efflux regulator AcrR from Escherichia coli., Biochem Biophys Res Commun 361(1):85-90

 [2] Lee JO., Cho KS., Kim OB., 2014, Overproduction of AcrR increases organic solvent tolerance mediated by modulation of SoxS regulon in Escherichia coli., Appl Microbiol Biotechnol 98(20):8763-73

 [3] Ma D., Alberti M., Lynch C., Nikaido H., Hearst JE., 1996, The local repressor AcrR plays a modulating role in the regulation of acrAB genes of Escherichia coli by global stress signals., Mol Microbiol 19(1):101-12

 [4] Rodionov DA., Gelfand MS., Mironov AA., Rakhmaninova AB., 2001, Comparative approach to analysis of regulation in complete genomes: multidrug resistance systems in gamma-proteobacteria., J Mol Microbiol Biotechnol 3(2):319-24

 [5] Kim YJ., Im SY., Lee JO., Kim OB., 2016, Potential Swimming Motility Variation by AcrR in Escherichia coli., J Microbiol Biotechnol 26(10):1824-1828

 [6] Li M, Gu R, Su CC, Routh MD, Harris KC, Jewell ES, McDermott G, Yu EW, 2007, Crystal structure of the transcriptional regulator AcrR from Escherichia coli., J Mol Biol, 374(3):591 10.1016/j.jmb.2007.09.064

 [7] Webber MA, Talukder A, Piddock LJ, 2005, Contribution of mutation at amino acid 45 of AcrR to acrB expression and ciprofloxacin resistance in clinical and veterinary Escherichia coli isolates., Antimicrob Agents Chemother, 49(10):4390 10.1128/AAC.49.10.4390-4392.2005

 [8] Colclough AL, Scadden J, Blair JMA, 2019, TetR-family transcription factors in Gram-negative bacteria: conservation, variation and implications for efflux-mediated antimicrobial resistance., BMC Genomics, 20(1):731 10.1186/s12864-019-6075-5

 [9] Routh MD, Su CC, Zhang Q, Yu EW, 2009, Structures of AcrR and CmeR: insight into the mechanisms of transcriptional repression and multi-drug recognition in the TetR family of regulators., Biochim Biophys Acta, 1794(5):844 10.1016/j.bbapap.2008.12.001


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