RegulonDB RegulonDB 10.7:Regulon Page

MarR DNA-binding transcriptional repressor

Synonyms: MarR-2,4-dinitrophenol, MarR-Benzoate, MarR-Menadione, MarR-Paraquat, MarR-Phenazine methosulfate, MarR-Plumbagin, MarR-Sodium salicylate, MarR, MarR-salicylate
MarA, "Multiple antibiotic resistance" [4], participates in controlling several genes involved in resistance to antibiotics, multidrug efflux [8, 9, 10], oxidative stress [11], organic solvents [12], and heavy metals [11]. MarR is part of the marRAB operon and negatively autoregulates its own expression [13]. The marA gene encodes a transcriptional activator that autoactivates expression of the marRAB operon and that regulates the expression of a global network of at least 80 chromosomal genes [13, 14, 15, 16], as well as expression of the marB gene, whose product has an unknown function [17]. Under laboratory conditions, the marRAB operon can be induced by tetracycline, chloramphenicol, or salicylate [1, 3, 18, 19, 20], plumbagin, dinitrophenol, and menadione [21], and other chemicals with phenolic rings [21].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
MarR Functional   Apo [APPH], [BPP], [GEA] [1], [2], [3]
MarR-2,4-dinitrophenol Non-Functional Allosteric Holo [BPP], [GEA] [3]
MarR-Benzoate Non-Functional Allosteric Holo [BPP], [GEA] [3]
MarR-Menadione Non-Functional Allosteric Holo [BPP], [GEA] [3]
MarR-Paraquat Non-Functional Allosteric Holo [BPP], [GEA] [3]
MarR-Phenazine methosulfate Non-Functional Allosteric Holo [BPP], [GEA] [3]
MarR-Plumbagin Non-Functional Allosteric Holo [BPP], [GEA] [3]
MarR-Sodium salicylate Non-Functional Allosteric Holo nd nd
MarR-salicylate Non-Functional Allosteric Holo [BPP], [GEA] [3]
Evolutionary Family: MarR
Connectivity class: Local Regulator
Gene name: marR
  Genome position: 1619120-1619554
  Length: 435 bp / 144 aa
Operon name: marRAB
TU(s) encoding the TF:
Transcription unit        Promoter

Regulated gene(s) marA, marB, marR
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
drug resistance/sensitivity (3)
Transcription related (2)
repressor (2)
operon (2)
detoxification (2)
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Regulated operon(s) marRAB
First gene in the operon(s) marR
Simple and complex regulons AcrR,CRP,CpxR,Cra,Fis,MarA,MarR,Rob,SoxS
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
  MarR repressor marRp Sigma70 -18.0 -45.0 marR, marA, marB
1619064 1619085 [AIBSCS], [APIORCISFBSCS], [BPP], [CV(GEA/GS)], [CV(GEA/SM/GS)], [GEA], [GS], [SM] [1], [2], [3], [4], [5], [6], [7]
  MarR repressor marRp Sigma70 17.0 -11.0 marR, marA, marB
1619098 1619119 [AIBSCS], [APIORCISFBSCS], [BPP], [CV(GEA/GS)], [CV(GEA/SM/GS)], [GEA], [GS], [SM] [1], [2], [3], [4], [5], [6], [7]

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


 [APPH] Assay of protein purified to homogeneity

 [BPP] Binding of purified proteins

 [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.

 [CV(GEA/GS)] cross validation(GEA/GS)

 [CV(GEA/SM/GS)] cross validation(GEA/SM/GS)

 [GS] genomic SELEX

 [SM] Site mutation


 [1] Martin RG., Rosner JL., 1995, Binding of purified multiple antibiotic-resistance repressor protein (MarR) to mar operator sequences., Proc Natl Acad Sci U S A 92(12):5456-60

 [2] Notka F., Linde HJ., Dankesreiter A., Niller HH., Lehn N., 2002, A C-terminal 18 amino acid deletion in MarR in a clinical isolate of Escherichia coli reduces MarR binding properties and increases the MIC of ciprofloxacin., J Antimicrob Chemother 49(1):41-7

 [3] Seoane AS., Levy SB., 1995, Characterization of MarR, the repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli., J Bacteriol 177(12):3414-9

 [4] Cohen SP., Hachler H., Levy SB., 1993, Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli., J Bacteriol 175(5):1484-92

 [5] Martin RG., Rosner JL., 2004, Transcriptional and translational regulation of the marRAB multiple antibiotic resistance operon in Escherichia coli., Mol Microbiol 53(1):183-91

 [6] 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

 [7] Shimada T., Ogasawara H., Ishihama A., 2018, Single-target regulators form a minor group of transcription factors in Escherichia coli K-12., Nucleic Acids Res 46(8):3921-3936

 [8] Ruiz C., Levy SB., 2010, Many chromosomal genes modulate MarA-mediated multidrug resistance in Escherichia coli., Antimicrob Agents Chemother 54(5):2125-34

 [9] Warner DM, Levy SB, 2010, Different effects of transcriptional regulators MarA, SoxS and Rob on susceptibility of Escherichia coli to cationic antimicrobial peptides (CAMPs): Rob-dependent CAMP induction of the marRAB operon., Microbiology, 2010 Feb

 [10] Keeney D, Ruzin A, McAleese F, Murphy E, Bradford PA, 2008, MarA-mediated overexpression of the AcrAB efflux pump results in decreased susceptibility to tigecycline in Escherichia coli., J Antimicrob Chemother, 2008 Jan

 [11] Alekshun MN, Levy SB, 1999, The mar regulon: multiple resistance to antibiotics and other toxic chemicals., Trends Microbiol, 1999 Oct

 [12] White DG, Goldman JD, Demple B, Levy SB, 1997, Role of the acrAB locus in organic solvent tolerance mediated by expression of marA, soxS, or robA in Escherichia coli., J Bacteriol, 1997 Oct

 [13] Alekshun MN, Levy SB, 1997, Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon., Antimicrob Agents Chemother, 1997 Oct

 [14] Pomposiello PJ., Bennik MH., Demple B., 2001, Genome-wide transcriptional profiling of the Escherichia coli responses to superoxide stress and sodium salicylate., J Bacteriol 183(13):3890-902

 [15] Barbosa TM, Levy SB, 2000, Differential expression of over 60 chromosomal genes in Escherichia coli by constitutive expression of MarA., J Bacteriol, 2000 Jun

 [16] Alekshun MN, Levy SB, Mealy TR, Seaton BA, Head JF, 2001, The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 A resolution., Nat Struct Biol, 2001 Aug

 [17] Domain F, Bina XR, Levy SB, 2007, Transketolase A, an enzyme in central metabolism, derepresses the marRAB multiple antibiotic resistance operon of Escherichia coli by interaction with MarR., Mol Microbiol, 2007 Oct

 [18] Cohen SP, Levy SB, Foulds J, Rosner JL, 1993, Salicylate induction of antibiotic resistance in Escherichia coli: activation of the mar operon and a mar-independent pathway., J Bacteriol, 1993 Dec

 [19] Hächler H, Cohen SP, Levy SB, 1991, marA, a regulated locus which controls expression of chromosomal multiple antibiotic resistance in Escherichia coli., J Bacteriol, 1991 Sep

 [20] 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

 [21] Alekshun MN, Levy SB, 1999, Alteration of the repressor activity of MarR, the negative regulator of the Escherichia coli marRAB locus, by multiple chemicals in vitro., J Bacteriol, 1999 Aug

 [22] Wilkinson SP, Grove A, 2006, Ligand-responsive transcriptional regulation by members of the MarR family of winged helix proteins., Curr Issues Mol Biol, 2006 Jan

 [23] Chubiz LM, Glekas GD, Rao CV, 2012, Transcriptional cross talk within the mar-sox-rob regulon in Escherichia coli is limited to the rob and marRAB operons., J Bacteriol, 2012 Sep

 [24] Domain F, Levy SB, 2010, GyrA interacts with MarR to reduce repression of the marRAB operon in Escherichia coli., J Bacteriol, 2010 Feb

 [25] McMurry LM, Levy SB, 2013, Amino acid residues involved in inactivation of the Escherichia coli multidrug resistance repressor MarR by salicylate, 2,4-dinitrophenol, and plumbagin., FEMS Microbiol Lett, 2013 Dec

 [26] Chubiz LM, Rao CV, 2010, Aromatic acid metabolites of Escherichia coli K-12 can induce the marRAB operon., J Bacteriol, 2010 Sep

 [27] Martin RG., Jair KW., Wolf RE., Rosner JL., 1996, Autoactivation of the marRAB multiple antibiotic resistance operon by the MarA transcriptional activator in Escherichia coli., J Bacteriol 178(8):2216-23

 [28] Linde HJ., Notka F., Metz M., Kochanowski B., Heisig P., Lehn N., 2000, In vivo increase in resistance to ciprofloxacin in Escherichia coli associated with deletion of the C-terminal part of MarR., Antimicrob Agents Chemother 44(7):1865-8

 [29] Zhu R, Hao Z, Lou H, Song Y, Zhao J, Chen Y, Zhu J, Chen PR, 2017, Structural characterization of the DNA-binding mechanism underlying the copper(II)-sensing MarR transcriptional regulator., J Biol Inorg Chem, 2017 Jul

 [30] Hulo N, Sigrist CJ, Le Saux V, Langendijk-Genevaux PS, Bordoli L, Gattiker A, De Castro E, Bucher P, Bairoch A, 2004, Recent improvements to the PROSITE database., Nucleic Acids Res, 2004 Jan 1

 [31] Alekshun MN, Kim YS, Levy SB, 2000, Mutational analysis of MarR, the negative regulator of marRAB expression in Escherichia coli, suggests the presence of two regions required for DNA binding., Mol Microbiol, 2000 Mar

 [32] Egland PG, Harwood CS, 1999, BadR, a new MarR family member, regulates anaerobic benzoate degradation by Rhodopseudomonas palustris in concert with AadR, an Fnr family member., J Bacteriol, 1999 Apr

 [33] Wu RY, Zhang RG, Zagnitko O, Dementieva I, Maltzev N, Watson JD, Laskowski R, Gornicki P, Joachimiak A, 2003, Crystal structure of Enterococcus faecalis SlyA-like transcriptional factor., J Biol Chem, 2003 May 30

 [34] Pérez-Rueda E, Collado-Vides J, 2001, Common history at the origin of the position-function correlation in transcriptional regulators in archaea and bacteria., J Mol Evol, 2001 Sep

 [35] Perez-Rueda E., Collado-Vides J., Segovia L., 2004, Phylogenetic distribution of DNA-binding transcription factors in bacteria and archaea., Comput Biol Chem 28(5-6):341-50

 [36] Doukyu N., Ishikawa K., Watanabe R., Ogino H., 2012, Improvement in organic solvent tolerance by double disruptions of proV and marR genes in Escherichia coli., J Appl Microbiol 112(3):464-74

 [37] Oh HY, Lee JO, Kim OB, 2012, Increase of organic solvent tolerance of Escherichia coli by the deletion of two regulator genes, fadR and marR., Appl Microbiol Biotechnol, 2012 Dec

 [38] Krisko A, Copic T, Gabaldón T, Lehner B, Supek F, 2014, Inferring gene function from evolutionary change in signatures of translation efficiency., Genome Biol, 2014 Mar 3

 [39] Deochand DK, Grove A, 2017, MarR family transcription factors: dynamic variations on a common scaffold., Crit Rev Biochem Mol Biol, 2017 Dec