EMRE_ECOLI
ID EMRE_ECOLI Reviewed; 110 AA.
AC P23895; Q2MBN8;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Multidrug transporter EmrE;
DE AltName: Full=Efflux-multidrug resistance protein EmrE;
DE AltName: Full=Ethidium resistance protein;
DE AltName: Full=Methyl viologen resistance protein C;
GN Name=emrE; Synonyms=eb, mvrC; OrderedLocusNames=b0543, JW0531;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1936950; DOI=10.1016/0378-1097(91)90338-b;
RA Purewal A.S.;
RT "Nucleotide sequence of the ethidium efflux gene from Escherichia coli.";
RL FEMS Microbiol. Lett. 66:229-231(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1320256; DOI=10.1093/nar/20.12.3159;
RA Morimyo M., Hongo E., Hama-Inaba H., Machida I.;
RT "Cloning and characterization of the mvrC gene of Escherichia coli K-12
RT which confers resistance against methyl viologen toxicity.";
RL Nucleic Acids Res. 20:3159-3165(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT "Sequence of minutes 4-25 of Escherichia coli.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [6]
RP FUNCTION, AND KINETIC PARAMETERS.
RC STRAIN=K12 / JM109 / ATCC 53323;
RX PubMed=7896833; DOI=10.1074/jbc.270.12.6856;
RA Yerushalmi H., Lebendiker M., Schuldiner S.;
RT "EmrE, an Escherichia coli 12-kDa multidrug transporter, exchanges toxic
RT cations and H+ and is soluble in organic solvents.";
RL J. Biol. Chem. 270:6856-6863(1995).
RN [7]
RP FUNCTION, AND REVIEW.
RX PubMed=9050242; DOI=10.1242/jeb.200.2.335;
RA Schuldiner S., Lebendiker M., Yerushalmi H.;
RT "EmrE, the smallest ion-coupled transporter, provides a unique paradigm for
RT structure-function studies.";
RL J. Exp. Biol. 200:335-341(1997).
RN [8]
RP FUNCTION, PH DEPENDENCE, AND MUTAGENESIS OF GLU-14.
RC STRAIN=K12 / JM109 / ATCC 53323;
RX PubMed=10681497; DOI=10.1074/jbc.275.8.5264;
RA Yerushalmi H., Schuldiner S.;
RT "An essential glutamyl residue in EmrE, a multidrug antiporter from
RT Escherichia coli.";
RL J. Biol. Chem. 275:5264-5269(2000).
RN [9]
RP FUNCTION.
RX PubMed=11574548; DOI=10.1074/jbc.m108231200;
RA Ninio S., Rotem D., Schuldiner S.;
RT "Functional analysis of novel multidrug transporters from human
RT pathogens.";
RL J. Biol. Chem. 276:48250-48256(2001).
RN [10]
RP REVIEW.
RX PubMed=11443233; DOI=10.1152/physiologyonline.2001.16.3.130;
RA Schuldiner S., Granot D., Mordoch S.S., Ninio S., Rotem D., Soskin M.,
RA Tate C.G., Yerushalmi H.;
RT "Small is mighty: EmrE, a multidrug transporter as an experimental
RT paradigm.";
RL News Physiol. Sci. 16:130-134(2001).
RN [11]
RP MUTAGENESIS OF LEU-7; ALA-10; ILE-11; GLU-14; GLY-17 AND THR-18.
RX PubMed=12590142; DOI=10.1074/jbc.m213120200;
RA Gutman N., Steiner-Mordoch S., Schuldiner S.;
RT "An amino acid cluster around the essential Glu-14 is part of the
RT substrate- and proton-binding domain of EmrE, a multidrug transporter from
RT Escherichia coli.";
RL J. Biol. Chem. 278:16082-16087(2003).
RN [12]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=15044024; DOI=10.1016/s0014-5793(04)00240-6;
RA Ninio S., Elbaz Y., Schuldiner S.;
RT "The membrane topology of EmrE - a small multidrug transporter from
RT Escherichia coli.";
RL FEBS Lett. 562:193-196(2004).
RN [13]
RP SUBUNIT.
RX PubMed=15111102; DOI=10.1016/s0014-5793(04)00228-5;
RA Ubarretxena-Belandia I., Tate C.G.;
RT "New insights into the structure and oligomeric state of the bacterial
RT multidrug transporter EmrE: an unusual asymmetric homo-dimer.";
RL FEBS Lett. 564:234-238(2004).
RN [14]
RP FUNCTION.
RX PubMed=15371426; DOI=10.1074/jbc.m408187200;
RA Rotem D., Schuldiner S.;
RT "EmrE, a multidrug transporter from Escherichia coli, transports monovalent
RT and divalent substrates with the same stoichiometry.";
RL J. Biol. Chem. 279:48787-48793(2004).
RN [15]
RP SUBUNIT.
RX PubMed=14755055; DOI=10.1073/pnas.0306533101;
RA Elbaz Y., Steiner-Mordoch S., Danieli T., Schuldiner S.;
RT "In vitro synthesis of fully functional EmrE, a multidrug transporter, and
RT study of its oligomeric state.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:1519-1524(2004).
RN [16]
RP MUTAGENESIS OF TRP-63, AND SUBUNIT.
RX PubMed=15882076; DOI=10.1021/bi050356t;
RA Elbaz Y., Tayer N., Steinfels E., Steiner-Mordoch S., Schuldiner S.;
RT "Substrate-induced tryptophan fluorescence changes in EmrE, the smallest
RT ion-coupled multidrug transporter.";
RL Biochemistry 44:7369-7377(2005).
RN [17]
RP SUBSTRATE-BINDING CAVITY.
RX PubMed=16049002; DOI=10.1074/jbc.m504910200;
RA Sharoni M., Steiner-Mordoch S., Schuldiner S.;
RT "Exploring the binding domain of EmrE, the smallest multidrug
RT transporter.";
RL J. Biol. Chem. 280:32849-32855(2005).
RN [18]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=15919996; DOI=10.1126/science.1109730;
RA Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.;
RT "Global topology analysis of the Escherichia coli inner membrane
RT proteome.";
RL Science 308:1321-1323(2005).
RN [19]
RP MUTAGENESIS OF TYR-4; TYR-6; TYR-40; TYR-53 AND TYR-60.
RX PubMed=16672221; DOI=10.1074/jbc.m602088200;
RA Rotem D., Steiner-Mordoch S., Schuldiner S.;
RT "Identification of tyrosine residues critical for the function of an ion-
RT coupled multidrug transporter.";
RL J. Biol. Chem. 281:18715-18722(2006).
RN [20]
RP SUBUNIT.
RX PubMed=17003034; DOI=10.1074/jbc.m607186200;
RA Soskine M., Mark S., Tayer N., Mizrachi R., Schuldiner S.;
RT "On parallel and antiparallel topology of a homodimeric multidrug
RT transporter.";
RL J. Biol. Chem. 281:36205-36212(2006).
RN [21]
RP TOPOLOGY OF MUTANT.
RX PubMed=20308069; DOI=10.1074/jbc.m110.108746;
RA Nasie I., Steiner-Mordoch S., Gold A., Schuldiner S.;
RT "Topologically random insertion of EmrE supports a pathway for evolution of
RT inverted repeats in ion-coupled transporters.";
RL J. Biol. Chem. 285:15234-15244(2010).
RN [22]
RP SUBUNIT, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=20551331; DOI=10.1074/jbc.m110.132621;
RA Amadi S.T., Koteiche H.A., Mishra S., McHaourab H.S.;
RT "Structure, dynamics, and substrate-induced conformational changes of the
RT multidrug transporter EmrE in liposomes.";
RL J. Biol. Chem. 285:26710-26718(2010).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=20508091; DOI=10.1126/science.1188950;
RA Seppaelae S., Slusky J.S., Lloris-Garcera P., Rapp M., von Heijne G.;
RT "Control of membrane protein topology by a single C-terminal residue.";
RL Science 328:1698-1700(2010).
RN [24]
RP SUBUNIT, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=22178925; DOI=10.1038/nature10703;
RA Morrison E.A., DeKoster G.T., Dutta S., Vafabakhsh R., Clarkson M.W.,
RA Bahl A., Kern D., Ha T., Henzler-Wildman K.A.;
RT "Antiparallel EmrE exports drugs by exchanging between asymmetric
RT structures.";
RL Nature 481:45-50(2011).
RN [25]
RP REVIEW.
RX PubMed=22100111; DOI=10.1016/j.sbi.2011.10.004;
RA Henzler-Wildman K.;
RT "Analyzing conformational changes in the transport cycle of EmrE.";
RL Curr. Opin. Struct. Biol. 22:38-43(2012).
RN [26]
RP FUNCTION.
RX PubMed=22942246; DOI=10.1128/jb.00666-12;
RA Bay D.C., Turner R.J.;
RT "Small multidrug resistance protein EmrE reduces host pH and osmotic
RT tolerance to metabolic quaternary cation osmoprotectants.";
RL J. Bacteriol. 194:5941-5948(2012).
RN [27]
RP FUNCTION.
RX PubMed=23042996; DOI=10.1128/jb.01318-12;
RA Nasie I., Steiner-Mordoch S., Schuldiner S.;
RT "New substrates on the block: clinically relevant resistances for EmrE and
RT homologues.";
RL J. Bacteriol. 194:6766-6770(2012).
RN [28]
RP SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-67.
RX PubMed=23920359; DOI=10.1016/j.jmb.2013.07.039;
RA Lloris-Garcera P., Slusky J.S., Seppaelae S., Priess M., Schaefer L.V.,
RA von Heijne G.;
RT "In vivo trp scanning of the small multidrug resistance protein EmrE
RT confirms 3D structure models'.";
RL J. Mol. Biol. 425:4642-4651(2013).
RN [29]
RP FUNCTION, ACTIVITY REGULATION, AND DOMAIN.
RX PubMed=24448799; DOI=10.1074/jbc.m113.535328;
RA Morrison E.A., Henzler-Wildman K.A.;
RT "Transported substrate determines exchange rate in the multidrug resistance
RT transporter EmrE.";
RL J. Biol. Chem. 289:6825-6836(2014).
RN [30]
RP FUNCTION.
RX PubMed=29114048; DOI=10.1073/pnas.1708671114;
RA Robinson A.E., Thomas N.E., Morrison E.A., Balthazor B.M.,
RA Henzler-Wildman K.A.;
RT "New free-exchange model of EmrE transport.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E10083-E10091(2017).
RN [31]
RP FUNCTION, AND DOMAIN.
RX PubMed=30287687; DOI=10.1074/jbc.ra118.005430;
RA Thomas N.E., Wu C., Morrison E.A., Robinson A.E., Werner J.P.,
RA Henzler-Wildman K.A.;
RT "The C terminus of the bacterial multidrug transporter EmrE couples drug
RT binding to proton release.";
RL J. Biol. Chem. 293:19137-19147(2018).
RN [32]
RP STRUCTURE BY NMR, AND SUBCELLULAR LOCATION.
RX PubMed=9688273; DOI=10.1046/j.1432-1327.1998.2540610.x;
RA Schwaiger M., Lebendiker M., Yerushalmi H., Coles M., Groeger A.,
RA Schwarz C., Schuldiner S., Kessler H.;
RT "NMR investigation of the multidrug transporter EmrE, an integral membrane
RT protein.";
RL Eur. J. Biochem. 254:610-619(1998).
RN [33]
RP STRUCTURE BY ELECTRON MICROSCOPY (7.5 ANGSTROMS) IN COMPLEX WITH THE DRUG
RP TPP(+), AND SUBUNIT.
RX PubMed=14633977; DOI=10.1093/emboj/cdg611;
RA Ubarretxena-Belandia I., Baldwin J.M., Schuldiner S., Tate C.G.;
RT "Three-dimensional structure of the bacterial multidrug transporter EmrE
RT shows it is an asymmetric homodimer.";
RL EMBO J. 22:6175-6181(2003).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS).
RX PubMed=14970332; DOI=10.1073/pnas.0400137101;
RA Ma C., Chang G.;
RT "Structure of the multidrug resistance efflux transporter EmrE from
RT Escherichia coli.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:2852-2857(2004).
RN [35]
RP ERRATUM OF PUBMED:14970332, AND RETRACTION NOTICE OF PUBMED:14970332.
RX PubMed=17360700; DOI=10.1073/pnas.0700711104;
RA Ma C., Chang G.;
RL Proc. Natl. Acad. Sci. U.S.A. 104:3668-3668(2007).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (3.7 ANGSTROMS) IN COMPLEX WITH THE DRUG TPP(+).
RX PubMed=16373573; DOI=10.1126/science.1119776;
RA Pornillos O., Chen Y.-J., Chen A.P., Chang G.;
RT "X-ray structure of the EmrE multidrug transporter in complex with a
RT substrate.";
RL Science 310:1950-1953(2005).
RN [37]
RP ERRATUM OF PUBMED:16373573, AND RETRACTION NOTICE OF PUBMED:16373573.
RX PubMed=17185584; DOI=10.1126/science.314.5807.1875b;
RA Chang G., Roth C.B., Reyes C.L., Pornillos O., Chen Y.J., Chen A.P.;
RL Science 314:1875-1875(2006).
RN [38] {ECO:0007744|PDB:2I68}
RP STRUCTURE BY ELECTRON MICROSCOPY (7.5 ANGSTROMS), 3D-STRUCTURE MODELING,
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=17005200; DOI=10.1016/j.jmb.2006.08.072;
RA Fleishman S.J., Harrington S.E., Enosh A., Halperin D., Tate C.G.,
RA Ben-Tal N.;
RT "Quasi-symmetry in the cryo-EM structure of EmrE provides the key to
RT modeling its transmembrane domain.";
RL J. Mol. Biol. 364:54-67(2006).
RN [39] {ECO:0007744|PDB:3B5D, ECO:0007744|PDB:3B61, ECO:0007744|PDB:3B62}
RP X-RAY CRYSTALLOGRAPHY (3.80 ANGSTROMS) OF APOPROTEIN AND IN COMPLEXES WITH
RP TPP, FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=18024586; DOI=10.1073/pnas.0709387104;
RA Chen Y.J., Pornillos O., Lieu S., Ma C., Chen A.P., Chang G.;
RT "X-ray structure of EmrE supports dual topology model.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:18999-19004(2007).
RN [40]
RP STRUCTURE BY ELECTRON MICROSCOPY, AND DOMAIN.
RX PubMed=18295794; DOI=10.1016/j.jmb.2008.01.056;
RA Korkhov V.M., Tate C.G.;
RT "Electron crystallography reveals plasticity within the drug binding site
RT of the small multidrug transporter EmrE.";
RL J. Mol. Biol. 377:1094-1103(2008).
CC -!- FUNCTION: Multidrug efflux protein that confers resistance to a wide
CC range of toxic compounds, including ethidium, methyl viologen,
CC acriflavine, tetraphenylphosphonium (TPP(+)), benzalkonium, propidium,
CC dequalinium and the aminoglycoside antibiotics streptomycin and
CC tobramycin (PubMed:7896833, PubMed:9050242, PubMed:10681497,
CC PubMed:11574548, PubMed:15371426, PubMed:18024586, PubMed:18295794,
CC PubMed:23042996, PubMed:24448799). Can also transport the
CC osmoprotectants betaine and choline (PubMed:22942246). The drug efflux
CC is coupled to an influx of protons (PubMed:7896833, PubMed:15371426,
CC PubMed:29114048). Can couple antiport of a drug to either one or two
CC protons, performing both electrogenic and electroneutral transport of a
CC single substrate (PubMed:29114048). Simultaneously binds and
CC cotransports proton and drug (PubMed:29114048, PubMed:30287687).
CC {ECO:0000269|PubMed:10681497, ECO:0000269|PubMed:11574548,
CC ECO:0000269|PubMed:15371426, ECO:0000269|PubMed:18024586,
CC ECO:0000269|PubMed:18295794, ECO:0000269|PubMed:22942246,
CC ECO:0000269|PubMed:23042996, ECO:0000269|PubMed:24448799,
CC ECO:0000269|PubMed:29114048, ECO:0000269|PubMed:30287687,
CC ECO:0000269|PubMed:7896833, ECO:0000269|PubMed:9050242}.
CC -!- ACTIVITY REGULATION: Substrate identity influences both the ground-
CC state and transition-state energies for the conformational exchange
CC process, emphasizing the coupling between substrate binding and
CC transport. {ECO:0000269|PubMed:24448799}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=247 uM for methyl viologen {ECO:0000269|PubMed:7896833};
CC Vmax=1572 nmol/min/mg enzyme with methyl viologen as substrate
CC {ECO:0000269|PubMed:7896833};
CC pH dependence:
CC Optimum pH is 8-8.5. Transport activity occurs from pH 7.5 to 9.
CC {ECO:0000269|PubMed:10681497};
CC -!- SUBUNIT: Homodimer (PubMed:14633977, PubMed:15111102, PubMed:14755055,
CC PubMed:15882076, PubMed:17003034, PubMed:18024586, PubMed:20551331,
CC PubMed:22178925, PubMed:23920359). Forms an antiparallel dimeric
CC structure (PubMed:17005200, PubMed:18024586, PubMed:20551331,
CC PubMed:22178925, PubMed:23920359). Also forms dimers of homodimers
CC (PubMed:14755055). {ECO:0000269|PubMed:14633977,
CC ECO:0000269|PubMed:14755055, ECO:0000269|PubMed:15111102,
CC ECO:0000269|PubMed:15882076, ECO:0000269|PubMed:17003034,
CC ECO:0000269|PubMed:17005200, ECO:0000269|PubMed:18024586,
CC ECO:0000269|PubMed:20551331, ECO:0000269|PubMed:22178925,
CC ECO:0000269|PubMed:23920359}.
CC -!- INTERACTION:
CC P23895; P23895: emrE; NbExp=2; IntAct=EBI-8789431, EBI-8789431;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:15044024,
CC ECO:0000269|PubMed:9688273}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15044024, ECO:0000269|PubMed:17005200,
CC ECO:0000269|PubMed:9688273}. Note=Forms antiparallel homodimers
CC (PubMed:17005200, PubMed:18024586, PubMed:20508091, PubMed:20551331,
CC PubMed:22178925, PubMed:23920359). The topology could be controlled by
CC a single positively charged residue placed in different locations
CC throughout the protein, including the very C terminus
CC (PubMed:20508091). {ECO:0000269|PubMed:17005200,
CC ECO:0000269|PubMed:18024586, ECO:0000269|PubMed:20508091,
CC ECO:0000269|PubMed:20551331, ECO:0000269|PubMed:22178925,
CC ECO:0000269|PubMed:23920359}.
CC -!- DOMAIN: Binds different substrates in the same active site
CC (PubMed:18295794, PubMed:22178925). Binding of the substrate induces
CC conformational changes of EmrE (PubMed:18295794, PubMed:20551331,
CC PubMed:22178925). The asymmetric antiparallel homodimer exchanges
CC between inward- and outward-facing states that are identical except
CC that they have opposite orientation in the membrane (PubMed:22178925,
CC PubMed:24448799). The conserved C-terminal tail is strongly coupled to
CC EmrE's drug-binding domain and participates in secondary gating of
CC EmrE-mediated proton/drug transport, occluding the binding pocket of
CC fully protonated EmrE in the absence of drug to prevent dissipative
CC proton transport (PubMed:30287687). {ECO:0000269|PubMed:18295794,
CC ECO:0000269|PubMed:20551331, ECO:0000269|PubMed:22178925,
CC ECO:0000269|PubMed:24448799, ECO:0000269|PubMed:30287687}.
CC -!- MISCELLANEOUS: Mutants designed to insert with biased topology are
CC functional regardless of the topology. {ECO:0000269|PubMed:20308069}.
CC -!- MISCELLANEOUS: Encoded by the cryptic lambdoid prophage DLP12.
CC -!- SIMILARITY: Belongs to the drug/metabolite transporter (DMT)
CC superfamily. Small multidrug resistance (SMR) (TC 2.A.7.1) family.
CC {ECO:0000305}.
CC -!- CAUTION: The membrane insertion topology of the two monomers was
CC controversial and some studies originally suggested a parallel
CC arrangement of the two monomers in the EmrE dimer. The antiparallel
CC dimeric structure is now the generally accepted functional topology.
CC {ECO:0000305, ECO:0000305|PubMed:15044024,
CC ECO:0000305|PubMed:17003034}.
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DR EMBL; Z11877; CAA77936.1; -; Genomic_DNA.
DR EMBL; M62732; AAA24190.1; -; Genomic_DNA.
DR EMBL; U82598; AAB40740.1; -; Genomic_DNA.
DR EMBL; U00096; AAC73644.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76318.1; -; Genomic_DNA.
DR PIR; JN0329; JN0329.
DR RefSeq; NP_415075.1; NC_000913.3.
DR RefSeq; WP_001070439.1; NZ_LN832404.1.
DR PDB; 2I68; EM; -; A/B=1-110.
DR PDB; 3B5D; X-ray; 3.80 A; A/B=1-110.
DR PDB; 3B61; X-ray; 4.50 A; A/B/C/D/E/F/G/H=1-110.
DR PDB; 3B62; X-ray; 4.40 A; A/B/C/D=1-110.
DR PDB; 7JK8; NMR; -; A/B=1-110.
DR PDB; 7MGX; X-ray; 3.13 A; A/B/E/F=1-110.
DR PDB; 7MH6; X-ray; 2.85 A; A/B=1-110.
DR PDB; 7SFQ; NMR; -; A/B=1-110.
DR PDB; 7SSU; X-ray; 3.22 A; A/B=1-110.
DR PDB; 7SV9; X-ray; 3.36 A; A/B=1-110.
DR PDB; 7SVX; X-ray; 3.90 A; A/B=1-110.
DR PDB; 7T00; X-ray; 3.91 A; A/B=1-110.
DR PDBsum; 2I68; -.
DR PDBsum; 3B5D; -.
DR PDBsum; 3B61; -.
DR PDBsum; 3B62; -.
DR PDBsum; 7JK8; -.
DR PDBsum; 7MGX; -.
DR PDBsum; 7MH6; -.
DR PDBsum; 7SFQ; -.
DR PDBsum; 7SSU; -.
DR PDBsum; 7SV9; -.
DR PDBsum; 7SVX; -.
DR PDBsum; 7T00; -.
DR AlphaFoldDB; P23895; -.
DR BMRB; P23895; -.
DR SMR; P23895; -.
DR BioGRID; 4259366; 101.
DR ComplexPortal; CPX-2121; EmrE multidrug transporter complex.
DR DIP; DIP-9505N; -.
DR STRING; 511145.b0543; -.
DR TCDB; 2.A.7.1.3; the drug/metabolite transporter (dmt) superfamily.
DR PaxDb; P23895; -.
DR PRIDE; P23895; -.
DR DNASU; 948442; -.
DR EnsemblBacteria; AAC73644; AAC73644; b0543.
DR EnsemblBacteria; BAE76318; BAE76318; BAE76318.
DR GeneID; 948442; -.
DR KEGG; ecj:JW0531; -.
DR KEGG; eco:b0543; -.
DR PATRIC; fig|1411691.4.peg.1735; -.
DR EchoBASE; EB0623; -.
DR eggNOG; COG2076; Bacteria.
DR HOGENOM; CLU_133067_0_2_6; -.
DR InParanoid; P23895; -.
DR OMA; ATTAMKY; -.
DR PhylomeDB; P23895; -.
DR BioCyc; EcoCyc:EMRE-MON; -.
DR BioCyc; MetaCyc:EMRE-MON; -.
DR SABIO-RK; P23895; -.
DR EvolutionaryTrace; P23895; -.
DR PRO; PR:P23895; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:1990207; C:EmrE multidrug transporter complex; IPI:ComplexPortal.
DR GO; GO:0016021; C:integral component of membrane; IDA:EcoliWiki.
DR GO; GO:0005887; C:integral component of plasma membrane; ISM:EcoCyc.
DR GO; GO:0016020; C:membrane; IDA:EcoliWiki.
DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR GO; GO:0015199; F:amino-acid betaine transmembrane transporter activity; IMP:EcoCyc.
DR GO; GO:0015297; F:antiporter activity; IDA:EcoliWiki.
DR GO; GO:0015220; F:choline transmembrane transporter activity; IMP:EcoCyc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0022857; F:transmembrane transporter activity; IDA:CACAO.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IDA:EcoCyc.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEP:EcoliWiki.
DR GO; GO:0015871; P:choline transport; IMP:EcoCyc.
DR GO; GO:0031460; P:glycine betaine transport; IMP:EcoCyc.
DR GO; GO:0006970; P:response to osmotic stress; IMP:EcoCyc.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:EcoliWiki.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; IDA:ComplexPortal.
DR GO; GO:0006805; P:xenobiotic metabolic process; IMP:EcoliWiki.
DR GO; GO:0042908; P:xenobiotic transport; IDA:EcoCyc.
DR InterPro; IPR000390; Small_drug/metabolite_transptr.
DR InterPro; IPR045324; Small_multidrug_res.
DR PANTHER; PTHR30561; PTHR30561; 1.
DR Pfam; PF00893; Multi_Drug_Res; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiport; Cell inner membrane; Cell membrane; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..110
FT /note="Multidrug transporter EmrE"
FT /id="PRO_0000108074"
FT TRANSMEM 4..21
FT /note="Helical; Name=1"
FT /evidence="ECO:0000305|PubMed:17005200"
FT TRANSMEM 34..52
FT /note="Helical; Name=2"
FT /evidence="ECO:0000305|PubMed:17005200"
FT TRANSMEM 58..80
FT /note="Helical; Name=3"
FT /evidence="ECO:0000305|PubMed:17005200"
FT TRANSMEM 87..104
FT /note="Helical; Name=4"
FT /evidence="ECO:0000305|PubMed:17005200"
FT SITE 4
FT /note="Required for proper coupling between the substrate
FT transport and the proton gradient"
FT SITE 14
FT /note="Essential for translocation and for substrate and
FT proton binding"
FT /evidence="ECO:0000305|PubMed:12590142,
FT ECO:0000305|PubMed:29114048"
FT SITE 40
FT /note="Involved in substrate binding"
FT SITE 60
FT /note="Involved in substrate binding"
FT SITE 63
FT /note="Involved in substrate binding"
FT SITE 110
FT /note="Important for activity"
FT /evidence="ECO:0000305|PubMed:30287687"
FT MUTAGEN 4
FT /note="Y->C: Still binds substrate. No transport activity
FT in the presence of a proton gradient, but still transports
FT substrate in the absence of a proton gradient. Resistance
FT to toxicants is abolished."
FT /evidence="ECO:0000269|PubMed:16672221"
FT MUTAGEN 4
FT /note="Y->F,W: No effect on resistance to toxicants."
FT /evidence="ECO:0000269|PubMed:16672221"
FT MUTAGEN 6
FT /note="Y->C,F,L: No effect on resistance to toxicants."
FT /evidence="ECO:0000269|PubMed:16672221"
FT MUTAGEN 7
FT /note="L->C: No substrate binding. Resistance to toxicants
FT is abolished."
FT /evidence="ECO:0000269|PubMed:12590142"
FT MUTAGEN 10
FT /note="A->C: Still binds substrate, with lower affinity.
FT Resistance to toxicants is abolished."
FT /evidence="ECO:0000269|PubMed:12590142"
FT MUTAGEN 11
FT /note="I->C: Still binds substrate, with lower affinity.
FT Resistance to toxicants is abolished."
FT /evidence="ECO:0000269|PubMed:12590142"
FT MUTAGEN 14
FT /note="E->C: No substrate binding. No transport activity.
FT Resistance to toxicants is abolished."
FT /evidence="ECO:0000269|PubMed:10681497,
FT ECO:0000269|PubMed:12590142"
FT MUTAGEN 14
FT /note="E->D: Still binds substrate. No transport activity
FT in the presence of a proton gradient, but still transports
FT substrate in the absence of a proton gradient. Resistance
FT to toxicants is abolished."
FT /evidence="ECO:0000269|PubMed:10681497,
FT ECO:0000269|PubMed:12590142"
FT MUTAGEN 17
FT /note="G->C: No substrate binding. Resistance to toxicants
FT is abolished."
FT /evidence="ECO:0000269|PubMed:12590142"
FT MUTAGEN 18
FT /note="T->C: Still binds substrate, with lower affinity.
FT Resistance to toxicants is abolished."
FT /evidence="ECO:0000269|PubMed:12590142"
FT MUTAGEN 40
FT /note="Y->C,F,L,M,S,T,V: Modifies substrate specificity."
FT /evidence="ECO:0000269|PubMed:16672221"
FT MUTAGEN 53
FT /note="Y->C: No effect on resistance to toxicants."
FT /evidence="ECO:0000269|PubMed:16672221"
FT MUTAGEN 60
FT /note="Y->C,F: Still binds substrate, with lower affinity.
FT Resistance to toxicants is abolished."
FT /evidence="ECO:0000269|PubMed:16672221"
FT MUTAGEN 63
FT /note="W->C,Y: No transport activity. Resistance to
FT toxicants is abolished."
FT /evidence="ECO:0000269|PubMed:15882076"
FT MUTAGEN 63
FT /note="W->F: Still binds substrate, with two-fold reduction
FT in substrate affinity. Resistance to toxicants is
FT abolished."
FT /evidence="ECO:0000269|PubMed:15882076"
FT MUTAGEN 67
FT /note="G->W: Major destabilizing effect on the dimer form."
FT /evidence="ECO:0000269|PubMed:23920359"
FT HELIX 6..26
FT /evidence="ECO:0007829|PDB:7JK8"
FT HELIX 33..51
FT /evidence="ECO:0007829|PDB:7JK8"
FT HELIX 56..76
FT /evidence="ECO:0007829|PDB:7JK8"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:7JK8"
FT HELIX 85..103
FT /evidence="ECO:0007829|PDB:7JK8"
SQ SEQUENCE 110 AA; 11958 MW; 775153FC47D6AE3D CRC64;
MNPYIYLGGA ILAEVIGTTL MKFSEGFTRL WPSVGTIICY CASFWLLAQT LAYIPTGIAY
AIWSGVGIVL ISLLSWGFFG QRLDLPAIIG MMLICAGVLI INLLSRSTPH
