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




Gene: mdtC Accession Numbers: G7115 (EcoCyc), b2076, ECK2072

Synonyms: yegO

Regulation Summary Diagram

Regulation summary diagram for mdtC

Component of: MdtABC-TolC multidrug efflux system (extended summary available)

Summary:
MdtC is a subunit of the MdtABC RND-type drug exporter. MdtB and MdtC comprise a heteromultimeric transmembrane complex [Kim10b]. A hydropathy profile indicates that MdtC contains 6 transmembrane segments [Nagakubo02].

Locations: inner membrane

Map Position: [2,156,410 -> 2,159,487] (46.48 centisomes, 167°)
Length: 3078 bp / 1025 aa

Molecular Weight of Polypeptide: 111.01 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0006877, EchoBASE:EB3811, EcoGene:EG14058, EcoliWiki:b2076, ModBase:P76399, OU-Microarray:b2076, PortEco:mdtC, PR:PRO_000023184, Pride:P76399, Protein Model Portal:P76399, RefSeq:NP_416580, RegulonDB:G7115, SMR:P76399, String:511145.b2076, UniProt:P76399

Relationship Links: InterPro:IN-FAMILY:IPR001036, InterPro:IN-FAMILY:IPR023931, InterPro:IN-FAMILY:IPR027463, Pfam:IN-FAMILY:PF00873, Prints:IN-FAMILY:PR00702

In Paralogous Gene Group: 131 (6 members)

Gene-Reaction Schematic

Gene-Reaction Schematic

Genetic Regulation Schematic

Genetic regulation schematic for mdtC


GO Terms:
Biological Process:
Inferred from experimentGO:0006855 - drug transmembrane transport [Nagakubo02, Baranova02]
Inferred by computational analysisInferred from experimentGO:0046618 - drug export [Kim10b, Nagakubo02]
Inferred by computational analysisGO:0006810 - transport [UniProtGOA11, GOA01]
Molecular Function:
Inferred from experimentGO:0005515 - protein binding [Kim10b]
Inferred by computational analysisInferred from experimentGO:0015307 - drug:proton antiporter activity [Kim10b, Nagakubo02]
Inferred by computational analysisGO:0005215 - transporter activity [GOA06, GOA01]
Cellular Component:
Inferred from experimentInferred by computational analysisGO:0005886 - plasma membrane [UniProtGOA11a, UniProtGOA11, GOA06, DiazMejia09, Daley05]
Inferred from experimentGO:0005887 - integral component of plasma membrane [Kim10b]
Inferred by computational analysisGO:0016020 - membrane [UniProtGOA11, GOA01]
Inferred by computational analysisGO:0016021 - integral component of membrane [UniProtGOA11]

MultiFun Terms: cell structuremembrane
transportElectrochemical potential driven transportersPorters (Uni-, Sym- and Antiporters)

Essentiality data for mdtC knockouts:

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

Credits:
Last-Curated 19-Jun-2012 by Mackie A, Macquarie University


Subunit of: MdtABC-TolC multidrug efflux system

Subunit composition of MdtABC-TolC multidrug efflux system = [(TolC)3][MdtC][MdtB]2[MdtA]
         TolC outer membrane channel = (TolC)3 (extended summary available)
                 TolC monomer = TolC
         MdtABC-TolC multidrug efflux system - membrane subunit = MdtC (summary available)
         MdtABC-TolC multidrug efflux system - membrane subunit = MdtB (summary available)
         MdtABC-TolC multidrug efflux transport system - putative membrane fusion protein = MdtA (summary available)

Summary:
In response regulator overproduction studies and deletion mutation experiments [Nagakubo02], [Baranova02] the mdtABC (yegMNO) genes were found to constitute a multidrug resistance cluster which is regulated by the response regulator BaeR. These genes code for an RND-type drug export complex, MdtABC, which confers resistance against bile salt derivatives, sodium dodecyl sulfate (SDS) and novobiocin. The complex is unusual in that the MdtBC subunits comprise a heteromultimeric transmembrane complex whereas typical RND transporters in E.coli are homotrimers. Sequence homology suggests that mdtA encodes a membrane fusion protein [Nagakubo02]. MdtABC also has an absolute requirement for the multifunctional outer membrane channel TolC for its function [Nagakubo02].

Purified, active trimers contain MdtB and MdtC in a 2:1 ratio [Kim10b]. Mutagenesis of residues predicted to be involved in the proton translocation pathway and in ligand binding in both subunits suggests potentially different functions for each subunit and indicates that the complex is unlikely to function using a similar mechanism to that proposed for homotrimeric RND type transporters [Kim10b, Kim12].

MdtAC was shown to confer bile salt, but not novobiocin, resistance [Nagakubo02] suggesting that the MdtC homomultimeric RND exporter may represent an evolutionally earlier version of the exporter which, with the addition of MdtB gained an increased range of resistance.


GO Terms:
Biological Process:
Inferred by computational analysisInferred from experimentGO:0006855 - drug transmembrane transport [Baranova02, Nagakubo02]
Molecular Function:
Inferred by computational analysisInferred from experimentGO:0015307 - drug:proton antiporter activity [Kim10b, Nagakubo02]

Credits:
Last-Curated 19-Jun-2012 by Mackie A, Macquarie University


Enzymatic reaction of: multidrug efflux

Inferred from experiment

Transport reaction diagram for multidrug efflux


Sequence Features

Protein sequence of MdtABC-TolC multidrug efflux system - membrane subunit with features indicated

Feature Class Location Citations Comment
Transmembrane-Region 7 -> 29
Inferred by computational analysis[UniProt15]
UniProt: Helical.
Transmembrane-Region 336 -> 353
Inferred by computational analysis[UniProt15]
UniProt: Helical.
Transmembrane-Region 360 -> 379
Inferred by computational analysis[UniProt15]
UniProt: Helical.
Transmembrane-Region 389 -> 411
Inferred by computational analysis[UniProt15]
UniProt: Helical.
Transmembrane-Region 431 -> 453
Inferred by computational analysis[UniProt15]
UniProt: Helical.
Transmembrane-Region 468 -> 490
Inferred by computational analysis[UniProt15]
UniProt: Helical.
Transmembrane-Region 853 -> 875
Inferred by computational analysis[UniProt15]
UniProt: Helical.
Transmembrane-Region 895 -> 917
Inferred by computational analysis[UniProt15]
UniProt: Helical.
Transmembrane-Region 948 -> 970
Inferred by computational analysis[UniProt15]
UniProt: Helical.
Transmembrane-Region 985 -> 1007
Inferred by computational analysis[UniProt15]
UniProt: Helical.


Sequence Pfam Features

Protein sequence of MdtABC-TolC multidrug efflux system - membrane subunit with features indicated

Feature Class Location Citations Comment
Pfam PF00873 4 -> 1008
Inferred by computational analysis[Finn14]
ACR_tran : AcrB/AcrD/AcrF family


Gene Local Context (not to scale -- see Genome Browser for correct scale)

Gene local context diagram

Transcription Units

Transcription-unit diagram

Transcription-unit diagram

Notes:

History:
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


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

Baranova02: Baranova N, Nikaido H (2002). "The baeSR two-component regulatory system activates transcription of the yegMNOB (mdtABCD) transporter gene cluster in Escherichia coli and increases its resistance to novobiocin and deoxycholate." J Bacteriol 184(15);4168-76. PMID: 12107134

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

Finn14: Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M (2014). "Pfam: the protein families database." Nucleic Acids Res 42(Database issue);D222-30. PMID: 24288371

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."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

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

Kim10b: Kim HS, Nagore D, Nikaido H (2010). "Multidrug efflux pump MdtBC of Escherichia coli is active only as a B2C heterotrimer." J Bacteriol 192(5);1377-86. PMID: 20038594

Kim12: Kim HS, Nikaido H (2012). "Different Functions of MdtB and MdtC Subunits in the Heterotrimeric Efflux Transporter MdtB(2)C Complex of Escherichia coli." Biochemistry 51(20);4188-97. PMID: 22559837

Nagakubo02: Nagakubo S, Nishino K, Hirata T, Yamaguchi A (2002). "The putative response regulator BaeR stimulates multidrug resistance of Escherichia coli via a novel multidrug exporter system, MdtABC." J Bacteriol 184(15);4161-7. PMID: 12107133

UniProt15: UniProt Consortium (2015). "UniProt version 2015-08 released on 2015-07-22." 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

GamaCastro08: Gama-Castro S, Jimenez-Jacinto V, Peralta-Gil M, Santos-Zavaleta A, Penaloza-Spinola MI, Contreras-Moreira B, Segura-Salazar J, Muniz-Rascado L, Martinez-Flores I, Salgado H, Bonavides-Martinez C, Abreu-Goodger C, Rodriguez-Penagos C, Miranda-Rios J, Morett E, Merino E, Huerta AM, Trevino-Quintanilla L, Collado-Vides J (2008). "RegulonDB (version 6.0): gene regulation model of Escherichia coli K-12 beyond transcription, active (experimental) annotated promoters and Textpresso navigation." Nucleic Acids Res 36(Database issue);D120-4. PMID: 18158297

Hirakawa05: Hirakawa H, Inazumi Y, Masaki T, Hirata T, Yamaguchi A (2005). "Indole induces the expression of multidrug exporter genes in Escherichia coli." Mol Microbiol 55(4);1113-26. PMID: 15686558

Nishino05: Nishino K, Honda T, Yamaguchi A (2005). "Genome-wide analyses of Escherichia coli gene expression responsive to the BaeSR two-component regulatory system." J Bacteriol 187(5);1763-72. PMID: 15716448


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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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