P23895 (EMRE_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Escherichia coli (strain K12) [Reference proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia › Escherichia coli

Protein attributes

Sequence length	110 AA.
Sequence status	Complete.
Protein existence	Evidence 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.13
Subunit structure	Homodimer; parallel. May also form dimer of homodimers. Binds substrate at the dimerization interface. Ref.12 Ref.14 Ref.15 Ref.19 Ref.23
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 process	Antiport Transport
Cellular component	Cell inner membrane Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glycine betaine transport Inferred from mutant phenotype PubMed 22942246. Source: EcoCyc response to DNA damage stimulus Inferred from expression pattern PubMed 11967071. Source: EcoliWiki response to osmotic stress Inferred from mutant phenotype PubMed 22942246. Source: EcoCyc xenobiotic metabolic process Inferred from mutant phenotype Ref.2. Source: EcoliWiki
Cellular_component	integral to plasma membrane Inferred from direct assay Ref.20. Source: EcoCyc
Molecular_function	amino-acid betaine transmembrane transporter activity Inferred from mutant phenotype PubMed 22942246. Source: EcoCyc choline transmembrane transporter activity Inferred from mutant phenotype PubMed 22942246. Source: EcoCyc drug:hydrogen antiporter activity Inferred from direct assay Ref.13Ref.6. Source: EcoCyc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 110

110

Multidrug transporter EmrE

PRO_0000108074

Regions

Topological domain

1 – 3

3

Cytoplasmic Ref.11 Ref.17

Transmembrane

4 – 21

18

Helical; Name=1

Topological domain

22 – 33

12

Periplasmic Ref.11 Ref.17

Transmembrane

34 – 52

19

Helical; Name=2

Topological domain

53 – 57

5

Cytoplasmic Ref.11 Ref.17

Transmembrane

58 – 81

24

Helical; Name=3

Topological domain

82 – 84

3

Periplasmic Ref.11 Ref.17

Transmembrane

85 – 105

21

Helical; Name=4

Topological domain

106 – 110

5

Cytoplasmic Ref.11 Ref.17

Sites

Site

4

1

Required for proper coupling between the substrate transport and the proton gradient

Site

14

1

Essential for translocation and for substrate and proton binding

Site

40

1

Involved in substrate binding

Site

60

1

Involved in substrate binding

Site

63

1

Involved in substrate binding

Experimental info

Mutagenesis

4

1

Y → 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.18

Mutagenesis

4

1

Y → F or W: No effect on resistance to toxicants. Ref.18

Mutagenesis

6

1

Y → C, F or L: No effect on resistance to toxicants. Ref.18

Mutagenesis

7

1

L → C: No substrate binding. Resistance to toxicants is abolished. Ref.10

Mutagenesis

10

1

A → C: Still binds substrate, with lower affinity. Resistance to toxicants is abolished. Ref.10

Mutagenesis

11

1

I → C: Still binds substrate, with lower affinity. Resistance to toxicants is abolished. Ref.10

Mutagenesis

14

1

E → C: No substrate binding. No transport activity. Resistance to toxicants is abolished. Ref.8 Ref.10

Mutagenesis

14

1

E → 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.10

Mutagenesis

17

1

G → C: No substrate binding. Resistance to toxicants is abolished. Ref.10

Mutagenesis

18

1

T → C: Still binds substrate, with lower affinity. Resistance to toxicants is abolished. Ref.10

Mutagenesis

40

1

Y → C, F, L, M, S, T or V: Modifies substrate specificity. Ref.18

Mutagenesis

53

1

Y → C: No effect on resistance to toxicants. Ref.18

Mutagenesis

60

1

Y → C or F: Still binds substrate, with lower affinity. Resistance to toxicants is abolished. Ref.18

Mutagenesis

63

1

W → C or Y: No transport activity. Resistance to toxicants is abolished. Ref.15

Mutagenesis

63

1

W → F: Still binds substrate, with two-fold reduction in substrate affinity. Resistance to toxicants is abolished. Ref.15

Secondary structure

1

.

.

.

.

.

.

.

.

.

110

Helix Strand Turn

Details...

Helix

5 – 20

16

Helix

35 – 51

17

Helix

59 – 79

21

Helix

88 – 103

16

Sequences

	Sequence		Length	Mass (Da)
	P23895 [UniParc]. Last modified November 1, 1991. Version 1. Checksum: 775153FC47D6AE3D	FASTA	110	11,958
	10 20 30 40 50 60 MNPYIYLGGA ILAEVIGTTL MKFSEGFTRL WPSVGTIICY CASFWLLAQT LAYIPTGIAY 70 80 90 100 110 AIWSGVGIVL ISLLSWGFFG QRLDLPAIIG MMLICAGVLI INLLSRSTPH

References

	« Hide 'large scale' referencesShow '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 277:1453-1474(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]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.
[21]	"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(+).
[22]	"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).
[23]	"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.
[24]	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.
[25]	"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.

PIR

JN0329.

RefSeq

NP_415075.1. NC_000913.2.
YP_488830.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I68	electron microscopy	-	A/B	1-110	[»]
3B5D	X-ray	3.80	A/B	1-110	[»]
3B61	X-ray	4.50	A/B/C/D/E/F/G/H	1-110	[»]
3B62	X-ray	4.40	A/B/C/D	1-110	[»]

ProteinModelPortal

P23895.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-9505N.

STRING

511145.b0543.

Protein family/group databases

TCDB

2.A.7.1.3. drug/metabolite transporter (DMT) superfamily.

Protocols and materials databases

DNASU

948442.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC73644; AAC73644; b0543.
BAE76318; BAE76318; BAE76318.

GeneID

12930372.
948442.

KEGG

ecj:Y75_p0528.
eco:b0543.

PATRIC

32116248. VBIEscCol129921_0564.

Organism-specific databases

EchoBASE

EB0623.

EcoGene

EG10629. emrE.

Phylogenomic databases

eggNOG

COG2076.

HOGENOM

HOG000268006.

KO

K03297.

OMA

MLTLVVR.

ProtClustDB

PRK09541.

Enzyme and pathway databases

BioCyc

EcoCyc:EMRE-MONOMER.
ECOL316407:JW0531-MONOMER.

Gene expression databases

Genevestigator

P23895.

Family and domain databases

InterPro

IPR000390. Small_multidrug_res.
[Graphical view]

Pfam

PF00893. Multi_Drug_Res. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P23895.

Entry information

Entry name

EMRE_ECOLI

Accession

Primary (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:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program