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P23895 (EMRE_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Multidrug transporter EmrE
Alternative name(s):
Efflux-multidrug resistance protein EmrE
Ethidium resistance protein
Methyl viologen resistance protein C
Gene names
Name:emrE
Synonyms:eb, mvrC
Ordered Locus Names:b0543, JW0531
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length110 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Multidrug transporter that expels positively charged hydrophobic drugs across the inner membrane of E.coli., thereby conferring resistance to a wide range of toxic compounds. The drug efflux is coupled to an influx of protons. Is involved in the resistance of E.coli cells to methyl viologen, ethidium bromide and acriflavine. Is also able to transport tetraphenylphosphonium (TPP+) and benzalkonium. Ref.6 Ref.8 Ref.9 Ref.14

Subunit structure

Homodimer; parallel. May also form dimer of homodimers. Binds substrate at the dimerization interface. Ref.13 Ref.15 Ref.16 Ref.20 Ref.24

Subcellular location

Cell inner membrane; Multi-pass membrane protein.

Miscellaneous

Encoded by the cryptic lambdoid prophage DLP12.

Sequence similarities

Belongs to the small multidrug resistance (SMR) protein family.

Caution

EM structures show an asymmetric dimer with the monomers in an antiparallel orientation, in contradiction with biochemical data and cross-linking studies, which demonstrated a parallel arrangement. Until now, EmrE with a parallel orientation is the only one to be shown to be fully functional.

Biophysicochemical properties

Kinetic parameters:

KM=247 µM for methyl viologen Ref.6

Vmax=1572 nmol/min/mg enzyme with methyl viologen as substrate

pH dependence:

Optimum pH is 8-8.5. Transport activity occurs from pH 7.5 to 9.

Ontologies

Keywords
   Biological processAntiport
Transport
   Cellular componentCell inner membrane
Cell membrane
Membrane
   DomainTransmembrane
Transmembrane helix
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to DNA damage stimulus

Inferred from expression pattern PubMed 11967071. Source: EcoliWiki

choline transport

Inferred from mutant phenotype PubMed 22942246. Source: EcoCyc

drug export

Inferred from direct assay Ref.14Ref.6. Source: GOC

glycine betaine transport

Inferred from mutant phenotype PubMed 22942246. Source: EcoCyc

response to drug

Inferred from mutant phenotype Ref.6. Source: EcoliWiki

response to osmotic stress

Inferred from mutant phenotype PubMed 22942246. Source: EcoCyc

transmembrane transport

Inferred from direct assay PubMed 22178925Ref.6. Source: GOC

transport

Inferred from direct assay PubMed 12356478. Source: EcoliWiki

xenobiotic metabolic process

Inferred from mutant phenotype Ref.2. Source: EcoliWiki

   Cellular_componentintegral component of membrane

Inferred from direct assay Ref.21. Source: EcoliWiki

integral component of plasma membrane

Inferred from direct assay Ref.21. Source: EcoCyc

membrane

Inferred from direct assay PubMed 12356478. Source: EcoliWiki

   Molecular_functionamino-acid betaine transmembrane transporter activity

Inferred from mutant phenotype PubMed 22942246. Source: EcoCyc

antiporter activity

Inferred from direct assay Ref.6. Source: EcoliWiki

choline transmembrane transporter activity

Inferred from mutant phenotype PubMed 22942246. Source: EcoCyc

drug:hydrogen antiporter activity

Inferred from direct assay Ref.14Ref.6. Source: EcoCyc

transmembrane transporter activity

Inferred from direct assay PubMed 22178925. Source: CACAO

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 110110Multidrug transporter EmrE
PRO_0000108074

Regions

Topological domain1 – 33Cytoplasmic Ref.12 Ref.18
Transmembrane4 – 2118Helical; Name=1
Topological domain22 – 3312Periplasmic Ref.12 Ref.18
Transmembrane34 – 5219Helical; Name=2
Topological domain53 – 575Cytoplasmic Ref.12 Ref.18
Transmembrane58 – 8124Helical; Name=3
Topological domain82 – 843Periplasmic Ref.12 Ref.18
Transmembrane85 – 10521Helical; Name=4
Topological domain106 – 1105Cytoplasmic Ref.12 Ref.18

Sites

Site41Required for proper coupling between the substrate transport and the proton gradient
Site141Essential for translocation and for substrate and proton binding
Site401Involved in substrate binding
Site601Involved in substrate binding
Site631Involved in substrate binding

Experimental info

Mutagenesis41Y → C: Still binds substrate. No transport activity in the presence of a proton gradient, but still transports substrate in the absence of a proton gradient. Resistance to toxicants is abolished. Ref.19
Mutagenesis41Y → F or W: No effect on resistance to toxicants. Ref.19
Mutagenesis61Y → C, F or L: No effect on resistance to toxicants. Ref.19
Mutagenesis71L → C: No substrate binding. Resistance to toxicants is abolished. Ref.11
Mutagenesis101A → C: Still binds substrate, with lower affinity. Resistance to toxicants is abolished. Ref.11
Mutagenesis111I → C: Still binds substrate, with lower affinity. Resistance to toxicants is abolished. Ref.11
Mutagenesis141E → C: No substrate binding. No transport activity. Resistance to toxicants is abolished. Ref.8 Ref.11
Mutagenesis141E → D: Still binds substrate. No transport activity in the presence of a proton gradient, but still transports substrate in the absence of a proton gradient. Resistance to toxicants is abolished. Ref.8 Ref.11
Mutagenesis171G → C: No substrate binding. Resistance to toxicants is abolished. Ref.11
Mutagenesis181T → C: Still binds substrate, with lower affinity. Resistance to toxicants is abolished. Ref.11
Mutagenesis401Y → C, F, L, M, S, T or V: Modifies substrate specificity. Ref.19
Mutagenesis531Y → C: No effect on resistance to toxicants. Ref.19
Mutagenesis601Y → C or F: Still binds substrate, with lower affinity. Resistance to toxicants is abolished. Ref.19
Mutagenesis631W → C or Y: No transport activity. Resistance to toxicants is abolished. Ref.16
Mutagenesis631W → F: Still binds substrate, with two-fold reduction in substrate affinity. Resistance to toxicants is abolished. Ref.16

Secondary structure

......... 110
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P23895 [UniParc].

Last modified November 1, 1991. Version 1.
Checksum: 775153FC47D6AE3D

FASTA11011,958
        10         20         30         40         50         60 
MNPYIYLGGA ILAEVIGTTL MKFSEGFTRL WPSVGTIICY CASFWLLAQT LAYIPTGIAY 

        70         80         90        100        110 
AIWSGVGIVL ISLLSWGFFG QRLDLPAIIG MMLICAGVLI INLLSRSTPH 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of the ethidium efflux gene from Escherichia coli."
Purewal A.S.
FEMS Microbiol. Lett. 66:229-231(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Cloning and characterization of the mvrC gene of Escherichia coli K-12 which confers resistance against methyl viologen toxicity."
Morimyo M., Hongo E., Hama-Inaba H., Machida I.
Nucleic Acids Res. 20:3159-3165(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Sequence of minutes 4-25 of Escherichia coli."
Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[4]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[5]"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[6]"EmrE, an Escherichia coli 12-kDa multidrug transporter, exchanges toxic cations and H+ and is soluble in organic solvents."
Yerushalmi H., Lebendiker M., Schuldiner S.
J. Biol. Chem. 270:6856-6863(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, KINETIC PARAMETERS.
Strain: K12 / JM109 / ATCC 53323.
[7]"EmrE, the smallest ion-coupled transporter, provides a unique paradigm for structure-function studies."
Schuldiner S., Lebendiker M., Yerushalmi H.
J. Exp. Biol. 200:335-341(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[8]"An essential glutamyl residue in EmrE, a multidrug antiporter from Escherichia coli."
Yerushalmi H., Schuldiner S.
J. Biol. Chem. 275:5264-5269(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PH DEPENDENCE, MUTAGENESIS OF GLU-14.
Strain: K12 / JM109 / ATCC 53323.
[9]"Functional analysis of novel multidrug transporters from human pathogens."
Ninio S., Rotem D., Schuldiner S.
J. Biol. Chem. 276:48250-48256(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Small is mighty: EmrE, a multidrug transporter as an experimental paradigm."
Schuldiner S., Granot D., Mordoch S.S., Ninio S., Rotem D., Soskin M., Tate C.G., Yerushalmi H.
News Physiol. Sci. 16:130-134(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[11]"An amino acid cluster around the essential Glu-14 is part of the substrate- and proton-binding domain of EmrE, a multidrug transporter from Escherichia coli."
Gutman N., Steiner-Mordoch S., Schuldiner S.
J. Biol. Chem. 278:16082-16087(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LEU-7; ALA-10; ILE-11; GLU-14; GLY-17 AND THR-18.
[12]"The membrane topology of EmrE - a small multidrug transporter from Escherichia coli."
Ninio S., Elbaz Y., Schuldiner S.
FEBS Lett. 562:193-196(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY.
[13]"New insights into the structure and oligomeric state of the bacterial multidrug transporter EmrE: an unusual asymmetric homo-dimer."
Ubarretxena-Belandia I., Tate C.G.
FEBS Lett. 564:234-238(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[14]"EmrE, a multidrug transporter from Escherichia coli, transports monovalent and divalent substrates with the same stoichiometry."
Rotem D., Schuldiner S.
J. Biol. Chem. 279:48787-48793(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"In vitro synthesis of fully functional EmrE, a multidrug transporter, and study of its oligomeric state."
Elbaz Y., Steiner-Mordoch S., Danieli T., Schuldiner S.
Proc. Natl. Acad. Sci. U.S.A. 101:1519-1524(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[16]"Substrate-induced tryptophan fluorescence changes in EmrE, the smallest ion-coupled multidrug transporter."
Elbaz Y., Tayer N., Steinfels E., Steiner-Mordoch S., Schuldiner S.
Biochemistry 44:7369-7377(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF TRP-63, SUBUNIT.
[17]"Exploring the binding domain of EmrE, the smallest multidrug transporter."
Sharoni M., Steiner-Mordoch S., Schuldiner S.
J. Biol. Chem. 280:32849-32855(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBSTRATE-BINDING CAVITY.
[18]"Global topology analysis of the Escherichia coli inner membrane proteome."
Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.
Science 308:1321-1323(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY [LARGE SCALE ANALYSIS].
Strain: K12 / MG1655 / ATCC 47076.
[19]"Identification of tyrosine residues critical for the function of an ion-coupled multidrug transporter."
Rotem D., Steiner-Mordoch S., Schuldiner S.
J. Biol. Chem. 281:18715-18722(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF TYR-4; TYR-6; TYR-40; TYR-53 AND TYR-60.
[20]"On parallel and antiparallel topology of a homodimeric multidrug transporter."
Soskine M., Mark S., Tayer N., Mizrachi R., Schuldiner S.
J. Biol. Chem. 281:36205-36212(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[21]"NMR investigation of the multidrug transporter EmrE, an integral membrane protein."
Schwaiger M., Lebendiker M., Yerushalmi H., Coles M., Groeger A., Schwarz C., Schuldiner S., Kessler H.
Eur. J. Biochem. 254:610-619(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[22]"Three-dimensional structure of the bacterial multidrug transporter EmrE shows it is an asymmetric homodimer."
Ubarretxena-Belandia I., Baldwin J.M., Schuldiner S., Tate C.G.
EMBO J. 22:6175-6181(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (7.5 ANGSTROMS) IN COMPLEX WITH THE DRUG TPP(+).
[23]"Structure of the multidrug resistance efflux transporter EmrE from Escherichia coli."
Ma C., Chang G.
Proc. Natl. Acad. Sci. U.S.A. 101:2852-2857(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS).
[24]"X-ray structure of the EmrE multidrug transporter in complex with a substrate."
Pornillos O., Chen Y.-J., Chen A.P., Chang G.
Science 310:1950-1953(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.7 ANGSTROMS) IN COMPLEX WITH THE DRUG TPP(+), SUBUNIT.
[25]Erratum
Chang G., Roth C.B., Reyes C.L., Pornillos O., Chen Y.J., Chen A.P.
Science 314:1875-1875(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: RETRACTION.
[26]"Quasi-symmetry in the cryo-EM structure of EmrE provides the key to modeling its transmembrane domain."
Fleishman S.J., Harrington S.E., Enosh A., Halperin D., Tate C.G., Ben-Tal N.
J. Mol. Biol. 364:54-67(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (7.5 ANGSTROMS), 3D-STRUCTURE MODELING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z11877 Genomic DNA. Translation: CAA77936.1.
M62732 Genomic DNA. Translation: AAA24190.1.
U82598 Genomic DNA. Translation: AAB40740.1.
U00096 Genomic DNA. Translation: AAC73644.1.
AP009048 Genomic DNA. Translation: BAE76318.1.
PIRJN0329.
RefSeqNP_415075.1. NC_000913.3.
YP_488830.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2I68electron microscopy-A/B1-110[»]
3B5DX-ray3.80A/B1-110[»]
3B61X-ray4.50A/B/C/D/E/F/G/H1-110[»]
3B62X-ray4.40A/B/C/D1-110[»]
ProteinModelPortalP23895.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-9505N.
STRING511145.b0543.

Protein family/group databases

TCDB2.A.7.1.3. the drug/metabolite transporter (dmt) superfamily.

Protocols and materials databases

DNASU948442.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC73644; AAC73644; b0543.
BAE76318; BAE76318; BAE76318.
GeneID12930372.
948442.
KEGGecj:Y75_p0528.
eco:b0543.
PATRIC32116248. VBIEscCol129921_0564.

Organism-specific databases

EchoBASEEB0623.
EcoGeneEG10629. emrE.

Phylogenomic databases

eggNOGCOG2076.
HOGENOMHOG000268006.
KOK03297.
OMAGVVYGTW.
OrthoDBEOG69WFSW.
PhylomeDBP23895.
ProtClustDBPRK09541.

Enzyme and pathway databases

BioCycEcoCyc:EMRE-MONOMER.
ECOL316407:JW0531-MONOMER.

Gene expression databases

GenevestigatorP23895.

Family and domain databases

InterProIPR000390. Small_multidrug_res.
[Graphical view]
PfamPF00893. Multi_Drug_Res. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP23895.
PROP23895.

Entry information

Entry nameEMRE_ECOLI
AccessionPrimary (citable) accession number: P23895
Secondary accession number(s): Q2MBN8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: April 16, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene