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



Gene: emrB Accession Numbers: EG11439 (EcoCyc), b2686, ECK2680

Regulation Summary Diagram: ?

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

Summary:
EmrB is a multidrug efflux protein. Expression of emrB has been shown to confer resistance to hydrophobic compounds such as carbonyl cyanide m-chlorophenylhydrazone, tetrachlorosalicylanilide, organomercurials and nalidixic acid [Lomovskaya92]. Disruption of emrB results in increased sensitivity to these compounds [Lomovskaya92]. EmrB has also been implicated in conferring resistance to thiolactomycin [Furukawa93]. EmrB is a member of the major facilitator superfamily, suggesting that it functions as a multidrug/proton antiporter.

emrB is co-transcribed with emrA, which encodes a member of the membrane fusion protein family [Lomovskaya92, Dinh94]. Genetic evidence has suggested that emrA and emrB may function together in conferring resistance. This suggests that EmrA and EmrB may form part of a complex mediating multidrug efflux. Transcriptional fusions have suggested that expression of ermA and emrB is negatively regulated by EmrR, whose gene is cotranscribed with emrA and emrB [Lomovskaya95]. CCCP, nalidixic acid and other substrates of EmrB have been shown to induce expression of emrB.

Locations: inner membrane

Map Position: [2,810,638 -> 2,812,176] (60.58 centisomes)
Length: 1539 bp / 512 aa

Molecular Weight of Polypeptide: 55.624 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0008840 , CGSC:33262 , EchoBASE:EB1409 , EcoGene:EG11439 , EcoliWiki:b2686 , ModBase:P0AEJ0 , OU-Microarray:b2686 , PortEco:emrB , PR:PRO_000022510 , Protein Model Portal:P0AEJ0 , RefSeq:NP_417171 , RegulonDB:EG11439 , SMR:P0AEJ0 , String:511145.b2686 , UniProt:P0AEJ0

Relationship Links: InterPro:IN-FAMILY:IPR004638 , InterPro:IN-FAMILY:IPR011701 , InterPro:IN-FAMILY:IPR016196 , InterPro:IN-FAMILY:IPR020846 , Pfam:IN-FAMILY:PF07690 , Prosite:IN-FAMILY:PS50850

In Paralogous Gene Group: 17 (37 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0009636 - response to toxic substance Inferred from experiment [Lomovskaya92]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0046677 - response to antibiotic Inferred by computational analysis [UniProtGOA11]
GO:0055085 - transmembrane transport Inferred by computational analysis [GOA01]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, DiazMejia09, Daley05]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11, GOA01]

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

Essentiality data for emrB 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

Summary:
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


Sequence Features

Feature Class Location Citations Comment
Transmembrane-Region 13 -> 38
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 52 -> 72
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 82 -> 100
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 110 -> 128
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 137 -> 159
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 165 -> 189
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 203 -> 223
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 234 -> 249
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 272 -> 295
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 306 -> 329
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Sequence-Conflict 325
[Lomovskaya92, UniProt10a]
Alternate sequence: G → A; UniProt: (in Ref. 1; AAA23725);
Transmembrane-Region 336 -> 355
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 364 -> 387
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 408 -> 428
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 482 -> 504
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Sequence-Conflict 501
[Lomovskaya92, UniProt10a]
Alternate sequence: P → A; UniProt: (in Ref. 1; AAA23725);
Protein-Segment 505 -> 510
[UniProt09]
UniProt: Poly-Gly; Sequence Annotation Type: compositionally biased region;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b2686 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11439; confirmed by SwissProt match.


References

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

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

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

Dinh94: Dinh T, Paulsen IT, Saier MH (1994). "A family of extracytoplasmic proteins that allow transport of large molecules across the outer membranes of gram-negative bacteria." J Bacteriol 1994;176(13);3825-31. PMID: 8021163

Furukawa93: 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

GOA01: 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

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

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

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

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

Other References Related to Gene Regulation

Hirakawa03: 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

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


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Wed Nov 26, 2014, biocyc13.