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

Gene: emrA Accession Numbers: EG11354 (EcoCyc), b2685, ECK2679

Regulation Summary Diagram: ?

Regulation summary diagram for emrA

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

EmrA is the membrane fusion protein for the EmrB multidrug efflux pump. The N-terminus of the protein is bound to the membrane while the C-terminal end is a soluble periplasmic domain. The protein can form dimers and trimers. The dimer form is more stable when membrane bound [BorgesWalmsley03]. Analysis of four tryptophan residues present in the periplasmic domain when subjected to the presence and absence of drugs revealed that EmrA is a drug-binding protein and is likely to play a role in the direct transfer of drugs from EmrB to TolC [BorgesWalmsley03].

Gene Citations: [Lomovskaya95]

Locations: inner membrane

Map Position: [2,809,449 -> 2,810,621] (60.55 centisomes, 218°)
Length: 1173 bp / 390 aa

Molecular Weight of Polypeptide: 42.736 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0008838 , CGSC:33259 , DIP:DIP-9502N , EchoBASE:EB1329 , EcoGene:EG11354 , EcoliWiki:b2685 , ModBase:P27303 , OU-Microarray:b2685 , PortEco:emrA , PR:PRO_000022509 , Pride:P27303 , Protein Model Portal:P27303 , RefSeq:NP_417170 , RegulonDB:EG11354 , SMR:P27303 , String:511145.b2685 , UniProt:P27303

Relationship Links: InterPro:IN-FAMILY:IPR005694 , InterPro:IN-FAMILY:IPR006143 , Pfam:IN-FAMILY:PF00529 , Prosite:IN-FAMILY:PS00543

In Paralogous Gene Group: 132 (13 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for emrA

GO Terms:

Biological Process: GO:0006810 - transport Inferred by computational analysis [UniProtGOA11a]
GO:0006855 - drug transmembrane transport Inferred by computational analysis [GOA01a]
GO:0046677 - response to antibiotic Inferred by computational analysis [UniProtGOA11a]
GO:0055085 - transmembrane transport Inferred by computational analysis [GOA01a]
Molecular Function: GO:0015238 - drug transmembrane transporter activity Inferred by computational analysis [GOA01a]
Cellular Component: GO:0031226 - intrinsic component of plasma membrane Inferred from experiment [Lomovskaya92]
GO:0031237 - intrinsic component of periplasmic side of plasma membrane Inferred from experiment [BorgesWalmsley03]
GO:0005886 - plasma membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11a]

MultiFun Terms: cell processes protection drug resistance/sensitivity
cell structure membrane
transport Electrochemical potential driven transporters Porters (Uni-, Sym- and Antiporters)

Essentiality data for emrA knockouts: ?

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

Subunit of: EmrAB-TolC multidrug efflux transport system

Subunit composition of EmrAB-TolC multidrug efflux transport system = [EmrA][EmrB][(TolC)3]
         EmrAB-TolC multidrug efflux transport system - membrane fusion protein = EmrA (summary available)
         EmrAB-TolC multidrug efflux transport system - membrane subunit = EmrB (extended summary available)
         TolC outer membrane channel = (TolC)3 (extended summary available)
                 TolC monomer = TolC

The EmrAB-TolC Drug Efflux System consists of the EmrA membrane fusion protein, the EmrB drug efflux pump (a member of the major facilitator superfamily), and TolC, the outer membrane protein that extrudes the drugs to the extracellular environment. One possible model of transport might be one in which EmrA and EmrB form a stable complex, possibly via their membrane-spanning leucine zipper motifs. The β-sheet domain of EmrA may be positioned above EmrB at the membrane surface with the α-helices of EmrA radiating across the periplasm to interact with TolC when triggered by the binding of drugs to the β-sheet domain of EmrA [BorgesWalmsley03]. Electron microscopy of reconstituted EmrAB complex suggests that the physiological form of EmrAB is a dimer [Tanabe09].

Locations: outer membrane, inner membrane, periplasmic space

GO Terms:

Cellular Component: GO:0005886 - plasma membrane
GO:0009279 - cell outer membrane
GO:0030288 - outer membrane-bounded periplasmic space

Enzymatic reaction of: multidrug efflux

Transport reaction diagram for multidrug efflux

Sequence Features

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

Feature Class Location Citations Comment
Transmembrane-Region 25 -> 45
UniProt: Helical.
Sequence-Conflict 62
[Lomovskaya92, UniProt10a]
UniProt: (in Ref. 1; AAA23724);
Sequence-Conflict 138
[Lomovskaya92, UniProt10a]
UniProt: (in Ref. 1; AAA23724);

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


10/20/97 Gene b2685 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11354; 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

BorgesWalmsley03: Borges-Walmsley MI, Beauchamp J, Kelly SM, Jumel K, Candlish D, Harding SE, Price NC, Walmsley AR (2003). "Identification of oligomerization and drug-binding domains of the membrane fusion protein EmrA." J Biol Chem 278(15);12903-12. PMID: 12482849

Furukawa93a: Furukawa H, Tsay JT, Jackowski S, Takamura Y, Rock CO (1993). "Thiolactomycin resistance in Escherichia coli is associated with the multidrug resistance efflux pump encoded by emrAB." J Bacteriol 1993;175(12);3723-9. PMID: 8509326

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."

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

Lomovskaya92: Lomovskaya O, Lewis K (1992). "Emr, an Escherichia coli locus for multidrug resistance." Proc Natl Acad Sci U S A 1992;89(19);8938-42. PMID: 1409590

Lomovskaya95: Lomovskaya O, Lewis K, Matin A (1995). "EmrR is a negative regulator of the Escherichia coli multidrug resistance pump EmrAB." J Bacteriol 1995;177(9);2328-34. PMID: 7730261

Tanabe09: Tanabe M, Szakonyi G, Brown KA, Henderson PJ, Nield J, Byrne B (2009). "The multidrug resistance efflux complex, EmrAB from Escherichia coli forms a dimer in vitro." Biochem Biophys Res Commun 380(2);338-42. PMID: 19171121

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." 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."

Other References Related to Gene Regulation

Hirakawa03a: Hirakawa H, Nishino K, Hirata T, Yamaguchi A (2003). "Comprehensive studies of drug resistance mediated by overexpression of response regulators of two-component signal transduction systems in Escherichia coli." J Bacteriol 185(6);1851-6. PMID: 12618449

Sakamoto15: 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. PMID: 25898225

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

Xiong00: 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. PMID: 10991887

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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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