mexX (PA2019) encodes MexX, the periplasmic adaptor (membrane fusion protein) of the MexXY-OprM resistance-nodulation-cell division (RND) multidrug efflux pump of Pseudomonas aeruginosa. MexX is an inner-membrane-anchored lipoprotein that links the inner-membrane RND transporter MexY to the outer-membrane channel OprM (or OpmB/OpmG/OpmI), forming a tripartite pump that expels aminoglycosides, tetracyclines, macrolides, fluoroquinolones and other drugs across both membranes. The mexXY operon is repressed by MexZ and is barely expressed in drug-free medium; ribosome-targeting antibiotics induce it, and MexXY is the main determinant of intrinsic aminoglycoside resistance.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:15325256 Role of the membrane fusion protein in the assembly of resis... | REMOVE | Summary: Bare protein binding with OprM from a pull-down study of MexAB-OprM and MexXY-OprM assembly. Reason: Uninformative under the protein-binding policy; removal does not dispute the MexX-OprM association. The adaptor role is captured by efflux pump complex and transmembrane transporter binding (MexY). Supporting Evidence: PMID:15325256 These results implied that the membrane fusion protein is central to the tripartite xenobiotic transporter assembly. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN001249140 (seeds E. coli AcrA, MdtE). MFPs of RND pumps are inner-membrane-anchored. Reason: MexX is a predicted lipoprotein anchored to the inner (cytoplasmic) membrane, as for other MFPs in this clade. Supporting Evidence: PMID:11114896 a periplasmic but cytoplasmic membrane-anchored membrane fusion protein ( 15 ) (MexA, MexC, MexE, and MexX) |
| GO:0005886 plasma membrane | IDA PMID:11083635 Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY... | ACCEPT | Summary: UniProt IDA from the MexAB/MexCD/MexXY substrate-specificity paper (abstract only). Reason: Consistent with the lipoprotein anchor and the MFP family; deferring to the curator, who read the full text. Supporting Evidence: PMID:11114896 a periplasmic but cytoplasmic membrane-anchored membrane fusion protein ( 15 ) (MexA, MexC, MexE, and MexX) |
| GO:0005886 plasma membrane | IDA PMID:15325256 Role of the membrane fusion protein in the assembly of resis... | ACCEPT | Summary: UniProt IDA from the pump-assembly pull-down paper (abstract only). Reason: Consistent with the lipoprotein anchor and the MFP family; deferring to the curator. Supporting Evidence: PMID:11114896 a periplasmic but cytoplasmic membrane-anchored membrane fusion protein ( 15 ) (MexA, MexC, MexE, and MexX) |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (cell inner membrane). Reason: Agrees with the IDA and IBA rows. Supporting Evidence: PMID:11114896 a periplasmic but cytoplasmic membrane-anchored membrane fusion protein ( 15 ) (MexA, MexC, MexE, and MexX) |
| GO:0015562 efflux transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN001249140 with MexA as the source. The tripartite pump has efflux transporter activity; MexX contributes as the adaptor. Reason: MexX is required for MexXY-OprM efflux. The activity belongs to the assembled pump, so contributes_to would be the more precise qualifier than enables for an adaptor; the claim is accepted. Supporting Evidence: PMID:10543738 Antibiotic accumulation studies confirmed that this new system is an energy-dependent active efflux system that pumps out aminoglycosides. |
| GO:0016020 membrane | IDA PMID:11083635 Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY... | TOO GENERAL | Summary: Membrane, from the same paper as the plasma membrane IDA row. Reason: Plasma membrane (GO:0005886), accepted in this review, is_a membrane. Supporting Evidence: PMID:11114896 a periplasmic but cytoplasmic membrane-anchored membrane fusion protein ( 15 ) (MexA, MexC, MexE, and MexX) |
| GO:0016020 membrane | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the MFP family signature. Reason: Plasma membrane (GO:0005886), accepted in this review, is_a membrane. Supporting Evidence: PMID:11114896 a periplasmic but cytoplasmic membrane-anchored membrane fusion protein ( 15 ) (MexA, MexC, MexE, and MexX) |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the MFP family signature. Reason: GO:0015562 efflux transmembrane transporter activity, accepted in this review, is_a transmembrane transporter activity. Supporting Evidence: PMID:10543738 Antibiotic accumulation studies confirmed that this new system is an energy-dependent active efflux system that pumps out aminoglycosides. |
| GO:0042597 periplasmic space | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping (periplasm). The adaptor domains of MexX lie in the periplasm, while the protein is anchored to the inner membrane. Reason: True for the soluble periplasmic domains of an inner-membrane-anchored adaptor; the functional location is the efflux pump complex in the inner membrane. Supporting Evidence: PMID:11114896 a periplasmic but cytoplasmic membrane-anchored membrane fusion protein ( 15 ) (MexA, MexC, MexE, and MexX) |
| GO:0044325 transmembrane transporter binding | IPI PMID:15325256 Role of the membrane fusion protein in the assembly of resis... | ACCEPT | Summary: Binding to the RND transporter MexY, from the assembly pull-down study (abstract only). Reason: Adaptor-to-transporter binding is the core of MFP function; the abstract shows that assembly is partner-specific, and the curator read the full text. Supporting Evidence: PMID:15325256 These results implied that the membrane fusion protein is central to the tripartite xenobiotic transporter assembly. PMID:15325256 None of the heterologous subunit combinations such as MexA+MexY(his)+OprM and MexX+MexB(his)+OprM showed interaction. |
| GO:0046677 response to antibiotic | EXP PMID:10952562 Contribution of the MexX-MexY-oprM efflux system to intrinsi... | KEEP AS NON CORE | Summary: PseudoCAP EXP from Masuda et al. 2000 (abstract only), a seed of the PTN001249140 IBD. Isogenic mutants and MexX induction by antibiotics. Seed verdict SOUND. Reason: Response to antibiotic is a true, conventional resistance-phenotype term for an efflux component, and mexXY is itself induced by ribosome-targeting antibiotics. The core role is export, captured by GO:0140330, so this is non-core; same call as for PA3677 (mexJ). Supporting Evidence: PMID:10952562 Loss of either MexXY or OprM from the MexAB-deficient mutant increased susceptibility to all agents tested PMID:10952562 These results suggest that MexXY induced by these agents is functionally associated with spontaneously expressed OprM and contributes to the intrinsic resistance to these agents. |
| GO:0046677 response to antibiotic | EXP PMID:16030228 Induction of the MexXY efflux pump in Pseudomonas aeruginosa... | KEEP AS NON CORE | Summary: PseudoCAP EXP from Jeannot et al. 2005 (full text read), a seed of the PTN001249140 IBD. mexXY is induced by ribosome-targeting antibiotics. Seed verdict SOUND. Reason: Response to antibiotic is a true, conventional resistance-phenotype term for an efflux component, and mexXY is itself induced by ribosome-targeting antibiotics. The core role is export, captured by GO:0140330, so this is non-core; same call as for PA3677 (mexJ). Supporting Evidence: PMID:16030228 MexXY is an inducible efflux system that contributes to the natural resistance of Pseudomonas aeruginosa to antibiotics. PMID:16030228 showed concentration-dependent induction of gene mexY by various ribosome inhibitors |
| GO:0046677 response to antibiotic | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from PTN001249140, seeded by E. coli AcrA and MdtE, MexA and MexX itself. MexX in its own WITH/FROM is expected. Reason: Response to antibiotic is a true, conventional resistance-phenotype term for an efflux component, and mexXY is itself induced by ribosome-targeting antibiotics. The core role is export, captured by GO:0140330, so this is non-core; same call as for PA3677 (mexJ). The IBD stands on the E. coli seeds alone. Supporting Evidence: PMID:10952562 Loss of either MexXY or OprM from the MexAB-deficient mutant increased susceptibility to all agents tested |
| GO:0046677 response to antibiotic | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO from IPR061505. Reason: Response to antibiotic is a true, conventional resistance-phenotype term for an efflux component, and mexXY is itself induced by ribosome-targeting antibiotics. The core role is export, captured by GO:0140330, so this is non-core; same call as for PA3677 (mexJ). Supporting Evidence: PMID:10952562 Loss of either MexXY or OprM from the MexAB-deficient mutant increased susceptibility to all agents tested |
| GO:0046677 response to antibiotic | IMP PMID:10543738 Involvement of an active efflux system in the natural resist... | KEEP AS NON CORE | Summary: UniProt IMP from Aires et al. 1999 (full text read): a Tn501 mexXY mutant is hypersusceptible to aminoglycosides, tetracycline and erythromycin, and complementation restores resistance. Reason: Response to antibiotic is a true, conventional resistance-phenotype term for an efflux component, and mexXY is itself induced by ribosome-targeting antibiotics. The core role is export, captured by GO:0140330, so this is non-core; same call as for PA3677 (mexJ). Supporting Evidence: PMID:10543738 Antibiotic accumulation studies confirmed that this new system is an energy-dependent active efflux system that pumps out aminoglycosides. |
| GO:0046677 response to antibiotic | IMP PMID:10952562 Contribution of the MexX-MexY-oprM efflux system to intrinsi... | KEEP AS NON CORE | Summary: PseudoCAP IMP from Masuda et al. 2000, a seed of the PTN001249140 IBD; isogenic deletion mutants. Seed verdict SOUND. Reason: Response to antibiotic is a true, conventional resistance-phenotype term for an efflux component, and mexXY is itself induced by ribosome-targeting antibiotics. The core role is export, captured by GO:0140330, so this is non-core; same call as for PA3677 (mexJ). Supporting Evidence: PMID:10952562 Loss of either MexXY or OprM from the MexAB-deficient mutant increased susceptibility to all agents tested |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the MFP family signature. Reason: GO:0140330 xenobiotic detoxification by transmembrane export across the cell outer membrane, accepted in this review, is_a transmembrane transport. Supporting Evidence: PMID:10543738 Antibiotic accumulation studies confirmed that this new system is an energy-dependent active efflux system that pumps out aminoglycosides. |
| GO:0140330 xenobiotic detoxification by transmembrane export across the cell outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN001249140, seeded by E. coli AcrA and AcrE (and MexA has the same term by IDA). Tripartite RND pumps export drugs across both membranes. Reason: MexXY-OprM is an energy-dependent tripartite efflux pump that needs the outer-membrane channel OprM; the term names the core process. Supporting Evidence: PMID:10543738 Antibiotic accumulation studies confirmed that this new system is an energy-dependent active efflux system that pumps out aminoglycosides. PMID:10952562 These results suggest that MexXY induced by these agents is functionally associated with spontaneously expressed OprM and contributes to the intrinsic resistance to these agents. PMID:11083635 Extrusion of aminoglycosides is specific to MexXY-OprM |
| GO:1990281 efflux pump complex | IDA PMID:15325256 Role of the membrane fusion protein in the assembly of resis... | ACCEPT | Summary: Efflux pump complex, from the pull-down assembly study (abstract only). Reason: MexX is the adaptor subunit of the tripartite MexXY-OprM pump. Supporting Evidence: PMID:15325256 These results implied that the membrane fusion protein is central to the tripartite xenobiotic transporter assembly. |
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Download this section (compressed HTML)Q: Jeannot et al. suggest a physiological role for MexXY beyond antibiotic efflux, linked to ribosome perturbation. What are its natural substrates?
Experiment: Reconstitute MexXY-OprM in proteoliposomes, as done for MexAB-OprM, to measure proton-coupled aminoglycoside transport and the requirement for MexX directly.
Type: in vitro transport assay
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