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MprA DNA-binding transcriptional repressor

Synonyms: MprA, MprA-2,4-dinitrophenol, MprA-Carbonyl cyanide m-chlorophenylhydrazone (CCCP), MprA-Carbonyl cyanide p-(trifluoro-methoxy)phenylhydrazone
Summary:
The E. coli multidrug resistance regulator [2, 5], EmrR, negatively regulates the transcription of genes that code for multidrug resistance pumps that extrude structurally unrelated antimicrobial agents from the cell [2, 4] and possibly it also represses a gene that codes for a porin [4]. When EmrR is overexpressed (the emrR gene in multicopy), it is able to repress the marRAB operon, which encodes two transcriptional regulators [6].
EmrR, which is also known as MprA, microcin production regulation, locus A [7], has also been shown to be a repressor of plasmid-encoded genes involved in microcin biosynthesis [7, 8, 9].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
MprA Functional   Apo [BPP], [GEA] [1], [2], [3]
MprA-2,4-dinitrophenol Non-Functional Allosteric Holo [BPP], [GEA] [1], [2], [3]
MprA-Carbonyl cyanide m-chlorophenylhydrazone (CCCP) Non-Functional Allosteric Holo [BPP], [GEA] [1], [2], [3]
MprA-Carbonyl cyanide p-(trifluoro-methoxy)phenylhydrazone Non-Functional Allosteric Holo [BPP], [GEA] [1], [2], [3]
Evolutionary Family: MarR
Connectivity class: Local Regulator
Gene name: mprA
  Genome position: 2810770-2811300
  Length: 531 bp / 176 aa
Operon name: mprA-emrAB
TU(s) encoding the TF:
Transcription unit        Promoter
mprA-emrAB
mprAp


Regulon       
Regulated gene(s) acrA, acrB, emrA, emrB, mprA, nmpC
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
drug resistance/sensitivity (5)
Porters (Uni-, Sym- and Antiporters) (4)
membrane (4)
Transcription related (1)
repressor (1)
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Regulated operon(s) acrAB, mprA-emrAB, nmpC
First gene in the operon(s) acrA, mprA, nmpC
Simple and complex regulons AcrR,EnvR,MarA,MprA,PhoP,Rob,SoxS
CRP,IHF,MprA,OmpR
MprA
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MprA,-](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
  MprA repressor acrAp Sigma70 -16.0 -95.0 acrA, acrB
tttacatacaTTTGTGAATGTATGTACCATAgcacgacgat
485704 485724 [AIBSCS] [4]
  MprA repressor mprAp Sigma70 -10.0 -33.0 mprA, emrA, emrB
ttatttgtcaCTGTCGTTACTATATCGGCTGaaattaatga
2810727 2810747 [BPP] [3]
  MprA repressor nmpCp nd -161.0 -206.0 nmpC
ttataaataaCAGCCGTTAATATAAATTGGCtaatagattt
577021 577041 [AIBSCS] [4]


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

 [GEA] Gene expression analysis

 [AIBSCS] Automated inference based on similarity to consensus sequences



Reference(s)    

 [1] Brooun A., Tomashek JJ., Lewis K., 1999, Purification and ligand binding of EmrR, a regulator of a multidrug transporter., J Bacteriol. 181(16):5131-3

 [2] Lomovskaya O., Lewis K., Matin A., 1995, EmrR is a negative regulator of the Escherichia coli multidrug resistance pump EmrAB., J Bacteriol. 177(9):2328-34

 [3] Xiong A., Gottman A., Park C., Baetens M., Pandza S., Matin A., 2000, The EmrR protein represses the Escherichia coli emrRAB multidrug resistance operon by directly binding to its promoter region., Antimicrob Agents Chemother. 44(10):2905-7

 [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] Lomovskaya O., Lewis K., 1992, Emr, an Escherichia coli locus for multidrug resistance., Proc Natl Acad Sci U S A. 89(19):8938-42

 [6] Sulavik MC., Gambino LF., Miller PF., 1995, The MarR repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli: prototypic member of a family of bacterial regulatory proteins involved in sensing phenolic compounds., Mol Med. 1(4):436-46

 [7] del Castillo I., Gomez JM., Moreno F., 1990, mprA, an Escherichia coli gene that reduces growth-phase-dependent synthesis of microcins B17 and C7 and blocks osmoinduction of proU when cloned on a high-copy-number plasmid., J Bacteriol. 172(1):437-45

 [8] del Castillo I., Gonzalez-Pastor JE., San Millan JL., Moreno F., 1991, Nucleotide sequence of the Escherichia coli regulatory gene mprA and construction and characterization of mprA-deficient mutants., J Bacteriol. 173(12):3924-9

 [9] Mao W., Siegele DA., 1998, Genetic analysis of the stationary phase-induced mcb operon promoter in Escherichia coli., Mol Microbiol. 27(2):415-24

 [10] Asensio C., Perez-Diaz JC., 1976, A new family of low molecular weight antibiotics from enterobacteria., Biochem Biophys Res Commun. 69(1):7-14

 [11] Dalrymple BP., Swadling Y., 1997, Expression of a Butyrivibrio fibrisolvens E14 gene (cinB) encoding an enzyme with cinnamoyl ester hydrolase activity is negatively regulated by the product of an adjacent gene (cinR)., Microbiology. 143 ( Pt 4):1203-10

 [12] Yang H., Wolff E., Kim M., Diep A., Miller JH., 2004, Identification of mutator genes and mutational pathways in Escherichia coli using a multicopy cloning approach., Mol Microbiol. 53(1):283-95

 [13] Sakamoto A., Terui Y., Yoshida T., Yamamoto T., Suzuki H., Yamamoto K., Ishihama A., Igarashi K., Kashiwagi K., 2015, Three Members of Polyamine Modulon under Oxidative Stress Conditions: Two Transcription Factors (SoxR and EmrR) and a Glutathione Synthetic Enzyme (GshA)., PLoS One. 10(4):e0124883

 [14] Lewis K., 2001, In search of natural substrates and inhibitors of MDR pumps., J Mol Microbiol Biotechnol. 3(2):247-54

 [15] Grkovic S., Brown MH., Skurray RA., 2002, Regulation of bacterial drug export systems., Microbiol Mol Biol Rev. 66(4):671-701, table of contents

 [16] Miller PF., Sulavik MC., 1996, Overlaps and parallels in the regulation of intrinsic multiple-antibiotic resistance in Escherichia coli., Mol Microbiol. 21(3):441-8



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