Transcription Factor
| Accessions: | ECK120005874 (RegulonDB 7.5) |
| Names: | MarA, MarA DNA-binding transcriptional dual regulator |
| Organisms: | ECK12 |
| Libraries: | RegulonDB 7.5 1 1 Salgado H, Peralta-Gil M, Gama-Castro S, Santos-Zavaleta A, Muniz-Rascado L, Garcia-Sotelo JS, Weiss V, Solano-Lira H, Martinez-Flores I, Medina-Rivera A, Salgado-Osorio G, Alquicira-Hernandez S, Alquicira-Hernandez K, Lopez-Fuentes A, Porron-Sotelo L, Huerta AM, Bonavides-Martinez C, Balderas-Martinez YI, Pannier L, Olvera M, Labastida A, Jimenez-Jacinto V, Vega-Alvarado L, Del Moral-Chavez V, Hernandez-Alvarez A, Morett E, Collado-Vides J. RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more. Nucleic Acids Res. 2013 Jan 1;41(D1):D203-D213. [Pubmed] |
| Notes: | MarA, multiple antibiotic resistance Cohen SP,1993 participates in controlling several genes involved in resistance to antibiotics, oxidative stress Alekshun MN,1999 organic solvents White DG,1997; Alekshun MN,1999; Asako H,1997 and heavy metals Alekshun MN,1999MarA, SoxS, and Rob are paralogous transcriptional regulators that show 45% amino acid identity between them Cohen SP,1993 the crystal structures for Rob Kwon HJ,2000and MarA Rhee S,1998confirm this similarity between them; They activate a common set of genes, but the expression and activity of each one of these proteins are induced by different signals: the activity of Rob is increased with dipyridyl, bile salts, or decanoate Rosner JL,2002; Rosenberg EY,2003, and the transcription of MarA and SoxS is increased by the aromatic weak acid salicylate Martin RG,2002and oxidative stress Demple B.,1996 respectively.Many genes are regulated by all three proteins; however, some genes are regulated only by one of them; The differential regulation of these genes might be caused by the degeneracy of their DNA-binding sites Pomposiello PJ,2003These three monomer proteins bind to the same DNA site, a degenerate 19-bp sequence known as the sox-mar-rob box, which has to be in a specific orientation and distance relative to the -35 and -10 boxes of the promoter Martin RG,1999; Wood TI,1999 In class I promoters, the activators bind upstream of the -35 box and are generally oriented in a backwards direction, while in class II promoters the proteins overlap the -35 promoter hexamer and generally are oriented in the forward direction Martin RG,1999; Wood TI,1999 In a subset of the class I promoters the sox-mar-rob box is separated by ~30 bp from the -10 hexamer but can be functional in either orientation Martin RG,1999; Wood TI,1999For MarA it was shown that the extent of activation at different promoters is only poorly correlated with the strength of MarA binding to the specific mar box Martin RG,2008 By using a computational model of transcriptional activation it was proposed that at the class I promoter of mar MarA increases the binding of RNA polymerase but not the occupancy; At the class II promoters of sodA and micF MarA can even decrease both RNA polymerase affinity and occupancy at the promoter; The model predicts that MarA increases the rate of transcription initiation while decreasing the overall presence of the transcription machinery at the promoter Wall ME,2009The sox-mar-rob box contains an invariant A at position 1, two recognition elements, the RE1 at postion 4-7 and RE2 at position 15-18, and a 7-bp A/T-rich spacer separating these elements Kwon HJ,2000; Dangi B,2001; Griffith KL,2001; There are more than 10,000 such binding sites per genome Griffith KL,2002 However, the majority of these sites are not functional because they are not in the proper orientation or distance relative to the promoter Martin RG,2002 Based on these findings, it was proposed that these proteins activate the transcription by a mechanism named DNA scanning or prerecruitment, which consists of the formation of the complex RNA polymerase transcriptional regulator in the absence of DNA, and then this complex scans the DNA to bind to appropriate sites Martin RG,2002; Griffith KL,2002These three proteins belong to the AraC/XylS family of transcriptional regulators Gallegos MT,1997 and as with other members of this family they have two helix-turn-helix (HTH) motifs for DNA binding, one of them, located in the N-terminal region, interacts with the element RE1 of the mar box, and the HTH located in the C-terminal region interacts with the element RE2 Griffith KL,2002; Rhee S,1998; Dangi B,2001 In the case of Rob, it appears that only one of two HTH motifs makes base-specific contact with DNA; this was observed for the micF promoter Kwon HJ,2000Cells carrying a MarA mutation in a glutamic acid residue (E89A) were able to express higher resistance to superoxides than those harboring wild-type MarA Martin RG,2011 Thus, MarA E89A acts more like SoxS than MarA in exhibiting greater activation and binding at the class I promoter Martin RG,2011marA is the second gene of the marRAB operon, which encodes an autorepressor (MarR) and an autoactivator (MarA) Cohen SP,1993 MarR is inactivated by salicylate, and then the operon is induced; Upon removal of the inducer (salicylate), MarA is degraded by the Lon protease Griffith KL,2004 and the binding of MarA with DNA or RNA polymerase protects it from degradation Shah IM,2006Reviews: Alekshun MN,1999; Demple B.,1996; Randall LP,2002; sequence-specific DNA binding transcription factor activity; DNA binding; transcription repressor activity; response to drug; xenobiotic metabolic process; transcription, DNA-dependent; transcription activator activity; cytoplasm; Transcription related; activator; repressor; operon; detoxification; drug resistance/sensitivity; response to antibiotic; regulation of transcription, DNA-dependent; sequence-specific DNA binding; intracellular |
| Length: | 128 |
| Pfam Domains: | 18-59 Bacterial regulatory helix-turn-helix proteins, AraC family 32-108 Helix-turn-helix domain 71-108 Bacterial regulatory helix-turn-helix proteins, AraC family |
| Sequence: (in bold interface residues) | 1 MSRRNTDAITIHSILDWIEDNLESPLSLEKVSERSGYSKWHLQRMFKKETGHSLGQYIRS 60 61 RKMTEIAQKLKESNEPILYLAERYGFESQQTLTRTFKNYFDVPPHKYRMTNMQGESRFLH 120 121 PLNHYNS* |
| Interface Residues: | 38, 39, 40, 41, 43, 44, 47, 89, 90, 93, 94, 98 |
| 3D-footprint Homologues: | 4hf1_A, 7vwz_G, 3w6v_A, 1xs9_A, 1zgw_A |
| Binding Motifs: | MarA dtTTrryadWwyGTGCyrT |
| Binding Sites: | ECK120011414 ECK120011423 ECK120011425 ECK120011585 ECK120011627 ECK120013181 ECK120013183 ECK120013185 ECK120013187 ECK120013189 ECK120016803 ECK120016806 ECK120016808 ECK120017138 ECK120017170 ECK120035046 ECK120051371 ECK125110174 |
| Publications: | Gallegos MT., Schleif R., Bairoch A., Hofmann K., Ramos JL. Arac/XylS family of transcriptional regulators. Microbiol Mol Biol Rev. 61(4):393-410 (1997). [Pubmed] Demple B. Redox signaling and gene control in the Escherichia coli soxRS oxidative stress regulon--a review. Gene. 179(1):53-7 (1996). [Pubmed] White DG., Goldman JD., Demple B., Levy SB. Role of the acrAB locus in organic solvent tolerance mediated by expression of marA, soxS, or robA in Escherichia coli. J Bacteriol. 179(19):6122-6 (1997). [Pubmed] Cohen SP., Hachler H., Levy SB. Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli. J Bacteriol. 175(5):1484-92 (1993). [Pubmed] Rosner JL., Dangi B., Gronenborn AM., Martin RG. Posttranscriptional activation of the transcriptional activator Rob by dipyridyl in Escherichia coli. J Bacteriol. 184(5):1407-16 (2002). [Pubmed] Rosenberg EY., Bertenthal D., Nilles ML., Bertrand KP., Nikaido H. Bile salts and fatty acids induce the expression of Escherichia coli AcrAB multidrug efflux pump through their interaction with Rob regulatory protein. Mol Microbiol. 48(6):1609-19 (2003). [Pubmed] Pomposiello PJ., Koutsolioutsou A., Carrasco D., Demple B. SoxRS-regulated expression and genetic analysis of the yggX gene of Escherichia coli. J Bacteriol. 185(22):6624-32 (2003). [Pubmed] Martin RG., Gillette WK., Rhee S., Rosner JL. Structural requirements for marbox function in transcriptional activation of mar/sox/rob regulon promoters in Escherichia coli: sequence, orientation and spatial relationship to the core promoter. Mol Microbiol. 34(3):431-41 (1999). [Pubmed] Wood TI., Griffith KL., Fawcett WP., Jair KW., Schneider TD., Wolf RE. Interdependence of the position and orientation of SoxS binding sites in the transcriptional activation of the class I subset of Escherichia coli superoxide-inducible promoters. Mol Microbiol. 34(3):414-30 (1999). [Pubmed] Kwon HJ., Bennik MH., Demple B., Ellenberger T. Crystal structure of the Escherichia coli Rob transcription factor in complex with DNA. Nat Struct Biol. 7(5):424-30 (2000). [Pubmed] Dangi B., Pelupessey P., Martin RG., Rosner JL., Louis JM., Gronenborn AM. Structure and dynamics of MarA-DNA complexes: an NMR investigation. J Mol Biol. 314(1):113-27 (2001). [Pubmed] Griffith KL., Wolf RE. Systematic mutagenesis of the DNA binding sites for SoxS in the Escherichia coli zwf and fpr promoters: identifying nucleotides required for DNA binding and transcription activation. Mol Microbiol. 40(5):1141-54 (2001). [Pubmed] Griffith KL., Shah IM., Myers TE., O'Neill MC., Wolf RE. Evidence for pre-recruitment as a new mechanism of transcription activation in Escherichia coli: the large excess of SoxS binding sites per cell relative to the number of SoxS molecules per cell. Biochem Biophys Res Commun. 291(4):979-86 (2002). [Pubmed] Martin RG., Gillette WK., Martin NI., Rosner JL. Complex formation between activator and RNA polymerase as the basis for transcriptional activation by MarA and SoxS in Escherichia coli. Mol Microbiol. 43(2):355-70 (2002). [Pubmed] Griffith KL., Wolf RE. A comprehensive alanine scanning mutagenesis of the Escherichia coli transcriptional activator SoxS: identifying amino acids important for DNA binding and transcription activation. J Mol Biol. 322(2):237-57 (2002). [Pubmed] Rhee S., Martin RG., Rosner JL., Davies DR. A novel DNA-binding motif in MarA: the first structure for an AraC family transcriptional activator. Proc Natl Acad Sci U S A. 95(18):10413-8 (1998). [Pubmed] Griffith KL., Shah IM., Wolf RE. Proteolytic degradation of Escherichia coli transcription activators SoxS and MarA as the mechanism for reversing the induction of the superoxide (SoxRS) and multiple antibiotic resistance (Mar) regulons. Mol Microbiol. 51(6):1801-16 (2004). [Pubmed] Randall LP., Woodward MJ. The multiple antibiotic resistance (mar) locus and its significance. Res Vet Sci. 72(2):87-93 (2002). [Pubmed] Alekshun MN., Levy SB. The mar regulon: multiple resistance to antibiotics and other toxic chemicals. Trends Microbiol. 7(10):410-3 (1999). [Pubmed] Shah IM., Wolf RE. Inhibition of Lon-dependent degradation of the Escherichia coli transcription activator SoxS by interaction with 'soxbox' DNA or RNA polymerase. Mol Microbiol. 60(1):199-208 (2006). [Pubmed] Martin RG., Rosner JL. Promoter discrimination at class I MarA regulon promoters mediated by glutamic acid 89 of the MarA transcriptional activator of Escherichia coli. J Bacteriol. 193(2):506-15 (2011). [Pubmed] Wall ME., Markowitz DA., Rosner JL., Martin RG. Model of transcriptional activation by MarA in Escherichia coli. PLoS Comput Biol. 5(12):e1000614 (2009). [Pubmed] Martin RG., Bartlett ES., Rosner JL., Wall ME. Activation of the Escherichia coli marA/soxS/rob regulon in response to transcriptional activator concentration. J Mol Biol. 380(2):278-84 (2008). [Pubmed] Asako H., Nakajima H., Kobayashi K., Kobayashi M., Aono R. Organic solvent tolerance and antibiotic resistance increased by overexpression of marA in Escherichia coli. Appl Environ Microbiol. 63(4):1428-33 (1997). [Pubmed] |
| Related annotations: | PaperBLAST |
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