Escherichia coli K-12 substr. MG1655 Polypeptide: MdtEF-TolC multidrug efflux transport system - membrane fusion protein

Gene: mdtE Accession Numbers: EG12240 (EcoCyc), b3513, ECK3497

Synonyms: yhiU

Regulation Summary Diagram

Regulation summary diagram for mdtE

Component of: MdtEF-TolC multidrug efflux transport system (extended summary available)

MdtE has similarity to AcrA, but production of MdtE does not suppress an acrA mutant defect in efflux function with AcrB [Elkins03]. An N-terminal MdtE fragment can be substituted for an N-terminal fragment of AcrA, indicating that the AcrA C terminus is required for proper function with AcrB [Elkins03].

MdtE is a component of the MdtEF multidrug transporter. Sequence similarity indicates that MdtF belongs to the resistance-nodulation-cell division (RND) transporter family and that MdtE belongs to the membrane fusion protein family [Nishino02]. The outer membrane channel TolC is also required for proper MdtEF transporter function [Zgurskaya00].

Gene Citations: [Hirakawa06]

Locations: inner membrane

Map Position: [3,657,255 -> 3,658,412] (78.83 centisomes, 284°)
Length: 1158 bp / 385 aa

Molecular Weight of Polypeptide: 41.191 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0011478, EchoBASE:EB2151, EcoGene:EG12240, EcoliWiki:b3513, ModBase:P37636, OU-Microarray:b3513, PortEco:mdtE, PR:PRO_000023185, Pride:P37636, Protein Model Portal:P37636, RefSeq:NP_417970, RegulonDB:EG12240, SMR:P37636, String:511145.b3513, Swiss-Model:P37636, UniProt:P37636

Relationship Links: InterPro:IN-FAMILY:IPR006143, Pfam:IN-FAMILY:PF13533, Pfam:IN-FAMILY:PF16576, Prosite:IN-FAMILY:PS51257

In Paralogous Gene Group: 132 (13 members)

Gene-Reaction Schematic

Gene-Reaction Schematic

Genetic Regulation Schematic

Genetic regulation schematic for mdtE

GO Terms:
Biological Process:
Inferred by computational analysisGO:0006810 - transport [UniProtGOA11a]
Inferred by computational analysisGO:0046677 - response to antibiotic [UniProtGOA11a]
Inferred by computational analysisGO:0055085 - transmembrane transport [GOA01a]
Cellular Component:
Inferred from experimentInferred by computational analysisGO:0005886 - plasma membrane [UniProtGOA11, UniProtGOA11a, DiazMejia09, Zhang07, LopezCampistrou05]
Inferred by computational analysisGO:0016020 - membrane [UniProtGOA11a, GOA01a]


Essentiality data for mdtE knockouts:

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enrichedYes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB LennoxYes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerolYes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucoseYes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Subunit of: MdtEF-TolC multidrug efflux transport system

Subunit composition of MdtEF-TolC multidrug efflux transport system = [(TolC)3][MdtE]3[MdtF]3
         TolC outer membrane channel = (TolC)3 (extended summary available)
                 TolC monomer = TolC
         MdtEF-TolC multidrug efflux transport system - membrane fusion protein = MdtE (summary available)
         MdtEF-TolC multidrug efflux transport system - permease subunit = MdtF (summary available)

Studies performed using overexpression of the response regulator EvgA conferred multiple drug resistance (MDR) to Escherichia coli cells lacking the AcrAB MDR transporter [Nishino01]. The plasmid-containing cells showed drug resistance against deoxycholate (>32-fold compared with control level), doxorubicin (64-fold), rhodamine 6G (16-fold), erythromycin (8-fold), crystal violet (8-fold), benzalkonium (8-fold), and sodium dodecyl sulfate (SDS) (4-fold). EvgA is known to positively regulate the gene expression of the drug resistance system EmrKY, but cells in which only EmrKY is overproduced acquire resistance only to deoxycholate (8-fold) [Nishino01a]. Deletion mutation studies were conducted [Nishino02] in which mdtEF was removed by chromosomal in-frame mutation. The mdtEF deletion strain showed no increased drug resistance (except for deoxycholate) when evgA was overexpressed. Since overexpression of EvgA normally confers an MDR phenotype, these results strongly suggest that the EvgA-induced MDR is due to stimulation of mdtEF gene expression.

Sequence similarity indicate that MdtF belongs to the resistance-nodulation-cell division (RND) transporter family and that MdtE belongs to the membrane fusion protein family [Nishino02]. The outer membrane channel TolC is also required for proper MdtEF transporter function [Zgurskaya00].

MdtE and MdtF were found as homotrimers within the inner membrane and assemble with trimeric TolC to form the efflux pump [Stenberg05].

Enzymatic reaction of: multidrug efflux

Inferred by computational analysisInferred from experiment

Transport reaction diagram for multidrug efflux

Sequence Features

Protein sequence of MdtEF-TolC multidrug efflux transport system - membrane fusion protein with features indicated

Feature Class Location Citations Comment
Signal-Sequence 1 -> 20
Inferred by computational analysis[UniProt15]
Lipid-Binding-Site 21
Inferred by computational analysis[UniProt15]
UniProt: N-palmitoyl cysteine.
Chain 21 -> 385
Author statement[UniProt15]
UniProt: Multidrug resistance protein MdtE.
Pfam PF13533 60 -> 108
Inferred by computational analysis[Finn14]
Biotin_lipoyl_2 : Biotin-lipoyl like
Pfam PF16576 154 -> 289
Inferred by computational analysis[Finn14]
HlyD_D23 : Barrel-sandwich domain of CusB or HlyD membrane-fusion

Gene Local Context (not to scale -- see Genome Browser for correct scale)

Gene local context diagram

Transcription Units

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b3513 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12240; confirmed by SwissProt match.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Elkins03: Elkins CA, Nikaido H (2003). "Chimeric analysis of AcrA function reveals the importance of its C-terminal domain in its interaction with the AcrB multidrug efflux pump." J Bacteriol 185(18);5349-56. PMID: 12949086

Finn14: Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M (2014). "Pfam: the protein families database." Nucleic Acids Res 42(Database issue);D222-30. PMID: 24288371

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Hirakawa06: Hirakawa H, Inazumi Y, Senda Y, Kobayashi A, Hirata T, Nishino K, Yamaguchi A (2006). "N-acetyl-d-glucosamine induces the expression of multidrug exporter genes, mdtEF, via catabolite activation in Escherichia coli." J Bacteriol 188(16);5851-8. PMID: 16885453

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Nishino01: Nishino K, Yamaguchi A (2001). "Analysis of a complete library of putative drug transporter genes in Escherichia coli." J Bacteriol 2001;183(20);5803-12. PMID: 11566977

Nishino01a: Nishino K, Yamaguchi A (2001). "Overexpression of the response regulator evgA of the two-component signal transduction system modulates multidrug resistance conferred by multidrug resistance transporters." J Bacteriol 183(4);1455-8. PMID: 11157960

Nishino02: Nishino K, Yamaguchi A (2002). "EvgA of the two-component signal transduction system modulates production of the yhiUV multidrug transporter in Escherichia coli." J Bacteriol 184(8);2319-23. PMID: 11914367

Stenberg05: Stenberg F, Chovanec P, Maslen SL, Robinson CV, Ilag LL, von Heijne G, Daley DO (2005). "Protein complexes of the Escherichia coli cell envelope." J Biol Chem 280(41);34409-19. PMID: 16079137

UniProt15: UniProt Consortium (2015). "UniProt version 2015-08 released on 2015-07-22." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Zgurskaya00: Zgurskaya HI, Nikaido H (2000). "Cross-linked complex between oligomeric periplasmic lipoprotein AcrA and the inner-membrane-associated multidrug efflux pump AcrB from Escherichia coli." J Bacteriol 2000;182(15);4264-7. PMID: 10894736

Zhang07: Zhang N, Chen R, Young N, Wishart D, Winter P, Weiner JH, Li L (2007). "Comparison of SDS- and methanol-assisted protein solubilization and digestion methods for Escherichia coli membrane proteome analysis by 2-D LC-MS/MS." Proteomics 7(4);484-93. PMID: 17309111

Other References Related to Gene Regulation

Deng13: Deng Z, Shan Y, Pan Q, Gao X, Yan A (2013). "Anaerobic expression of the gadE-mdtEF multidrug efflux operon is primarily regulated by the two-component system ArcBA through antagonizing the H-NS mediated repression." Front Microbiol 4;194. PMID: 23874328

Eguchi03: Eguchi Y, Oshima T, Mori H, Aono R, Yamamoto K, Ishihama A, Utsumi R (2003). "Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli." Microbiology 149(Pt 10);2819-28. PMID: 14523115

Hommais04: Hommais F, Krin E, Coppee JY, Lacroix C, Yeramian E, Danchin A, Bertin P (2004). "GadE (YhiE): a novel activator involved in the response to acid environment in Escherichia coli." Microbiology 150(Pt 1);61-72. PMID: 14702398

Itou09: Itou J, Eguchi Y, Utsumi R (2009). "Molecular mechanism of transcriptional cascade initiated by the EvgS/EvgA system in Escherichia coli K-12." Biosci Biotechnol Biochem 73(4);870-8. PMID: 19352034

Krin10: Krin E, Danchin A, Soutourina O (2010). "Decrypting the H-NS-dependent regulatory cascade of acid stress resistance in Escherichia coli." BMC Microbiol 10;273. PMID: 21034467

Ma04: Ma Z, Masuda N, Foster JW (2004). "Characterization of EvgAS-YdeO-GadE branched regulatory circuit governing glutamate-dependent acid resistance in Escherichia coli." J Bacteriol 186(21);7378-89. PMID: 15489450

Marzan13: Marzan LW, Hasan CM, Shimizu K (2013). "Effect of acidic condition on the metabolic regulation of Escherichia coli and its phoB mutant." Arch Microbiol 195(3);161-71. PMID: 23274360

Nishino08: Nishino K, Senda Y, Yamaguchi A (2008). "CRP regulator modulates multidrug resistance of Escherichia coli by repressing the mdtEF multidrug efflux genes." J Antibiot (Tokyo) 61(3);120-7. PMID: 18503189

Nishino08a: Nishino K, Senda Y, Yamaguchi A (2008). "The AraC-family regulator GadX enhances multidrug resistance in Escherichia coli by activating expression of mdtEF multidrug efflux genes." J Infect Chemother 14(1);23-9. PMID: 18297445

Pesavento12: Pesavento C, Hengge R (2012). "The global repressor FliZ antagonizes gene expression by σS-containing RNA polymerase due to overlapping DNA binding specificity." Nucleic Acids Res 40(11);4783-93. PMID: 22323519

Sayed07: Sayed AK, Odom C, Foster JW (2007). "The Escherichia coli AraC-family regulators GadX and GadW activate gadE, the central activator of glutamate-dependent acid resistance." Microbiology 153(Pt 8);2584-92. PMID: 17660422

Sayed09: Sayed AK, Foster JW (2009). "A 750 bp sensory integration region directs global control of the Escherichia coli GadE acid resistance regulator." Mol Microbiol 71(6);1435-50. PMID: 19220752

Tramonti08: Tramonti A, De Canio M, De Biase D (2008). "GadX/GadW-dependent regulation of the Escherichia coli acid fitness island: transcriptional control at the gadY-gadW divergent promoters and identification of four novel 42 bp GadX/GadW-specific binding sites." Mol Microbiol 70(4);965-82. PMID: 18808381

Tucker03: Tucker DL, Tucker N, Ma Z, Foster JW, Miranda RL, Cohen PS, Conway T (2003). "Genes of the GadX-GadW regulon in Escherichia coli." J Bacteriol 185(10);3190-201. PMID: 12730179

Vinella12: Vinella D, Potrykus K, Murphy H, Cashel M (2012). "Effects on Growth by Changes of the Balance between GreA, GreB, and DksA Suggest Mutual Competition and Functional Redundancy in Escherichia coli." J Bacteriol 194(2);261-73. PMID: 22056927

Viveiros07: Viveiros M, Dupont M, Rodrigues L, Couto I, Davin-Regli A, Martins M, Pages JM, Amaral L (2007). "Antibiotic stress, genetic response and altered permeability of E. coli." PLoS ONE 2;e365. PMID: 17426813

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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