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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: ?

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 [Kim10f]. 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)
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: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006855 - drug transmembrane transport Inferred from experiment [Nagakubo02, Baranova02]
GO:0046618 - drug export Inferred by computational analysis Inferred from experiment [Kim10f, Nagakubo02]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Kim10f]
GO:0015307 - drug:proton antiporter activity Inferred by computational analysis Inferred from experiment [Kim10f, Nagakubo02]
GO:0005215 - transporter activity Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, DiazMejia09, Daley05]
GO:0005887 - integral component of plasma membrane Inferred from experiment [Kim10f]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11a]

MultiFun Terms: cell structure membrane
transport Electrochemical potential driven transporters Porters (Uni-, Sym- and Antiporters)

Essentiality data for mdtC 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]

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 [Kim10f]. 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 [Kim10f, Kim12a].

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: GO:0006855 - drug transmembrane transport Inferred by computational analysis Inferred from experiment [Baranova02, Nagakubo02]
Molecular Function: GO:0015307 - drug:proton antiporter activity Inferred by computational analysis Inferred from experiment [Kim10f, Nagakubo02]

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


Enzymatic reaction of: multidrug efflux


Sequence Features

Feature Class Location Citations Comment
Transmembrane-Region 7 -> 29
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 336 -> 353
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 360 -> 379
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 389 -> 411
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 431 -> 453
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 468 -> 490
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 853 -> 875
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 895 -> 917
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 948 -> 970
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 985 -> 1007
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;


Gene Local Context (not to scale): ?

Transcription Units:

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

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

GOA01a: 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

Kim10f: 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

Kim12a: 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

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

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

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords 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


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 Thu Dec 18, 2014, BIOCYC13A.