MdtABC-TolC multidrug efflux transport complex

cellstructuremech:mdtabc_tolc_multidrug_efflux_transport_complex · Other · Multiprotein complex · Proposed

An Escherichia coli Resistance-Nodulation-Division-family cell-envelope efflux pump complex composed of MdtA, MdtB, MdtC, and TolC subunits that exports novobiocin, bile salts, quinolones, fosfomycin, detergents, myricetin, zinc, and other substrates from the cell. [ComplexPortal:CPX-2119]

UniProt location names: UniProt Consortium, CC BY 4.0. Reference label and route sources.

Components

Component	Type	Part of / acts on	Grounding	Genes	Stoichiometry	Essential	Role
Multidrug resistance protein MdtA	Protein	part of	`InterPro:IPR022824`	mdtA		ESSENTIAL	Periplasmic membrane-fusion adaptor constituent of the MdtABC-TolC tripartite efflux system. `ComplexPortal:CPX-2119` Complex Portal CPX-2119 curates P76397/MdtA as an E. coli K-12 MdtABC-TolC multidrug efflux transport complex participant. `UniProtKB:P76397` UniProtKB P76397 is the reviewed E. coli K-12 entry for Multidrug resistance protein MdtA. `InterPro:IPR022824` InterPro IPR022824 is the Multidrug resistance protein MdtA family entry.
Multidrug resistance protein MdtB	Protein	part of	`InterPro:IPR022831`	mdtB	2 copies in the E. coli K-12 Complex Portal CPX-2119 entry	ESSENTIAL	Inner-membrane RND transporter subunit that dimerizes with MdtC to form the active MdtBC transport core. `ComplexPortal:CPX-2119` Complex Portal CPX-2119 curates P76398/MdtB as two copies in the E. coli K-12 MdtABC-TolC multidrug efflux transport complex. `UniProtKB:P76398` UniProtKB P76398 is the reviewed E. coli K-12 entry for Multidrug resistance protein MdtB. `InterPro:IPR022831` InterPro IPR022831 is the Multidrug resistance protein MdtB family entry.
Multidrug resistance protein MdtC	Protein	part of	`InterPro:IPR023931`	mdtC	1 copy in the E. coli K-12 Complex Portal CPX-2119 entry	ESSENTIAL	Inner-membrane RND transporter subunit that pairs with the MdtB dimer to complete the MdtBC transport core. `ComplexPortal:CPX-2119` Complex Portal CPX-2119 curates P76399/MdtC as one copy in the E. coli K-12 MdtABC-TolC multidrug efflux transport complex. `UniProtKB:P76399` UniProtKB P76399 is the reviewed E. coli K-12 entry for Multidrug resistance protein MdtC. `InterPro:IPR023931` InterPro IPR023931 is the Multidrug resistance protein MdtC family entry.
Outer membrane channel protein TolC	Protein	part of	`InterPro:IPR058622`	tolC	3 copies in the E. coli K-12 Complex Portal CPX-2119 entry	ESSENTIAL	Trimeric outer-membrane channel constituent that completes the MdtABC-TolC cell-envelope efflux conduit. `ComplexPortal:CPX-2119` Complex Portal CPX-2119 curates P02930/TolC as three copies in the E. coli K-12 MdtABC-TolC multidrug efflux transport complex. `UniProtKB:P02930` UniProtKB P02930 is the reviewed E. coli K-12 entry for Outer membrane protein TolC. `InterPro:IPR058622` InterPro IPR058622 is the Outer membrane channel protein TolC family entry.

Organism-specific protein examples

Named proteins in which each component's role was established, with the organism the evidence comes from. The component above is the taxon-agnostic family; these are the specific entries behind it.

Multidrug resistance protein MdtA

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P76397`	Multidrug resistance protein MdtA	mdtA	Escherichia coli K-12 (`NCBITaxon:83333`)	REVIEWED
Role and evidence (1 reference) `UniProtKB:P76397` Reviewed Swiss-Prot entry MDTA_ECOLI is the E. coli K-12 MdtA accession and cross-references ComplexPortal:CPX-2119.

Multidrug resistance protein MdtB

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P76398`	Multidrug resistance protein MdtB	mdtB	Escherichia coli K-12 (`NCBITaxon:83333`)	REVIEWED
Role and evidence (1 reference) `UniProtKB:P76398` Reviewed Swiss-Prot entry MDTB_ECOLI is the E. coli K-12 MdtB accession and cross-references ComplexPortal:CPX-2119.

Multidrug resistance protein MdtC

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P76399`	Multidrug resistance protein MdtC	mdtC	Escherichia coli K-12 (`NCBITaxon:83333`)	REVIEWED
Role and evidence (1 reference) `UniProtKB:P76399` Reviewed Swiss-Prot entry MDTC_ECOLI is the E. coli K-12 MdtC accession and cross-references ComplexPortal:CPX-2119.

Outer membrane channel protein TolC

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P02930`	Outer membrane protein TolC	tolC	Escherichia coli K-12 (`NCBITaxon:83333`)	REVIEWED
Role and evidence (1 reference) `UniProtKB:P02930` Reviewed Swiss-Prot entry TOLC_ECOLI is the E. coli K-12 TolC accession and cross-references ComplexPortal:CPX-2119.

Source composition assertions

MdtABC-TolC multidrug efflux transport complex (ComplexPortal:CPX-2119)

Escherichia coli (strain K12) (NCBITaxon:83333) · ECO:0005547 · retrieved 2026-10-02

Participant	Source type	Source name	Stoichiometry
`UniProtKB:P76399` — Multidrug resistance protein MdtC	protein	mdtC	1
`UniProtKB:P76397` — Multidrug resistance protein MdtA	protein	mdtA	not asserted
`UniProtKB:P76398` — Multidrug resistance protein MdtB	protein	mdtB	2
`UniProtKB:P02930` — Outer membrane protein TolC	protein	tolC	3

Curator-scoped import: E. coli K-12 MdtABC-TolC source composition for this record. Source evidence: inferred by curator. CPX-2119 does not supply an assembly label, and its MdtA participant has no source stoichiometry, so both fields are omitted here. The accession was resolved through the Complex Portal accession endpoint; no equivalence xref was inferred.

Canonical examples

NCBITaxon:83333 Escherichia coli K-12 — Source strain for Complex Portal CPX-2119, which curates MdtA, MdtB, MdtC, and TolC as the participants of MdtABC-TolC. [ComplexPortal:CPX-2119]

Functions

xenobiotic transmembrane transporter activity GO:0042910 — The MdtABC-TolC complex exports novobiocin, bile salts, quinolones, fosfomycin, detergents, myricetin, zinc, and other substrates from E. coli through the coupled MdtBC transporter, MdtA adaptor, and TolC channel.
- GO:0042910 GO:0042910 is the molecular-function term for xenobiotic transmembrane transporter activity.
- ComplexPortal:CPX-2119 Complex Portal cross-references GO:0042910 for the E. coli K-12 MdtABC-TolC multidrug efflux transport complex.

Mechanism graphs

MdtABC-TolC exports xenobiotics across the cell envelope (FUNCTION)

MdtB, MdtC, MdtA, and TolC form an envelope-spanning RND efflux pump that exports drug substrates and other xenobiotics from E. coli.

Subject	Predicate	Object	Evidence
Multidrug resistance protein MdtB	couples to	Multidrug resistance protein MdtC	`ComplexPortal:CPX-2119` CPX-2119 curates MdtB and MdtC as linked participants in the E. coli MdtABC-TolC pump.
Multidrug resistance protein MdtC	couples to	Multidrug resistance protein MdtA	`ComplexPortal:CPX-2119` CPX-2119 curates MdtA, MdtB, and MdtC as participants in the E. coli MdtABC-TolC pump.
Multidrug resistance protein MdtA	couples to	Outer membrane channel protein TolC	`UniProtKB:P76397` UniProtKB reports that MdtABC forms a tripartite efflux system and requires TolC for function.
MdtABC-TolC multidrug efflux transport complex	enables	xenobiotic transmembrane transporter activity	`ComplexPortal:CPX-2119` Complex Portal cross-references GO:0042910 for the MdtABC-TolC complex.
xenobiotic transmembrane transporter activity	transports	xenobiotic substrate	`ComplexPortal:CPX-2119` CPX-2119 summarizes the MdtABC-TolC complex as exporting novobiocin, bile salts, quinolones, fosfomycin, detergents, myricetin, and zinc.
xenobiotic detoxification by transmembrane export across the cell outer membrane	targets	cell exterior	`GO:0140330` GO:0140330 describes reducing xenobiotic toxicity by export through the outer membrane.

Evidence

ComplexPortal:CPX-2119 Complex Portal entry for the E. coli K-12 MdtABC-TolC multidrug efflux transport complex.
GO:1990281 Gene Ontology cellular-component parent term for efflux pump complexes.
GO:0042910 Gene Ontology molecular-function term for xenobiotic transmembrane transporter activity.
GO:0140330 Gene Ontology biological-process term for xenobiotic detoxification by transmembrane export across the cell outer membrane.
InterPro:IPR022824 InterPro family entry for Multidrug resistance protein MdtA.
InterPro:IPR022831 InterPro family entry for Multidrug resistance protein MdtB.
InterPro:IPR023931 InterPro family entry for Multidrug resistance protein MdtC.
InterPro:IPR058622 InterPro family entry for Outer membrane channel protein TolC.
UniProtKB:P76397 Reviewed E. coli K-12 MdtA UniProtKB entry.
UniProtKB:P76398 Reviewed E. coli K-12 MdtB UniProtKB entry.
UniProtKB:P76399 Reviewed E. coli K-12 MdtC UniProtKB entry.
UniProtKB:P02930 Reviewed E. coli K-12 TolC UniProtKB entry.
PMID:12107133 PubMed identifier for Nagakubo et al. 2002, The putative response regulator BaeR stimulates multidrug resistance of Escherichia coli via a novel multidrug exporter system, MdtABC.
DOI:10.1128/JB.184.15.4161-4167.2002 DOI for Nagakubo et al. 2002, The putative response regulator BaeR stimulates multidrug resistance of Escherichia coli via a novel multidrug exporter system, MdtABC.
PMID:20038594 PubMed identifier for Kim et al. 2010, Multidrug efflux pump MdtBC of Escherichia coli is active only as a B2C heterotrimer.
DOI:10.1128/JB.01448-09 DOI for Kim et al. 2010, Multidrug efflux pump MdtBC of Escherichia coli is active only as a B2C heterotrimer.
PMID:26113845 PubMed identifier for Anes et al. 2015, The ins and outs of RND efflux pumps in Escherichia coli.
DOI:10.3389/fmicb.2015.00587 DOI for Anes et al. 2015, The ins and outs of RND efflux pumps in Escherichia coli.

Curation history

2026-10-02T11:21:04Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-02T11:22:18Z codex · EXPANDED_RECORD — Added CPX-2119/GO efflux-pump parentage, MdtA, MdtB, MdtC, and TolC component rows with exact InterPro groundings and E. coli K-12 reviewed UniProt examples, a compact xenobiotic export graph, and the Complex Portal CPX-2119 source composition.
2026-10-02T11:37:53Z codex · REFINED_EVIDENCE_NOTES — Adjusted MdtABC-TolC substrate wording to avoid presenting zinc as a xenobiotic while preserving the CPX-2119 substrate list.

Source: data/structures/other/mdtabc_tolc_multidrug_efflux_transport_complex.yaml