PmpM (PA1361) is a multidrug efflux pump of the MATE (multidrug and toxic compound extrusion) family in Pseudomonas aeruginosa, an integral inner-membrane protein with 12 predicted transmembrane helices. Unlike the Na+-coupled MATE pumps first characterized in Vibrio and E. coli, PmpM couples drug export to the proton gradient, acting as an H+/drug antiporter. It extrudes cationic antimicrobials, including the disinfectant benzalkonium chloride, ethidium, acriflavine and tetraphenylphosphonium, and when over-expressed also fluoroquinolones. Together with MexCD-OprJ it is a major determinant of benzalkonium chloride resistance in P. aeruginosa.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IDA PMID:14679249 An H(+)-coupled multidrug efflux pump, PmpM, a member of the... | ACCEPT | Summary: PseudoCAP IDA and a seed of the PTN000129144 membrane IBD. H+/benzalkonium antiport was measured in everted membrane vesicles from E. coli expressing pmpM. Reason: Activity in inner-membrane vesicles, with 12 predicted TM helices, places the pump in the cytoplasmic membrane, where it acts. Seed verdict SOUND. Supporting Evidence: PMID:14679249 Addition of benzalkonium chloride to the assay mixture caused efflux of H + , indicating that H + -benzalkonium chloride antiport took place. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt location mapping (cell inner membrane, multi-pass). Reason: Agrees with the IDA row and the 12-helix topology. Supporting Evidence: PMID:14679249 Addition of benzalkonium chloride to the assay mixture caused efflux of H + , indicating that H + -benzalkonium chloride antiport took place. |
| GO:0015297 antiporter activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO from the MATE family. PmpM was shown to be an H+/drug antiporter whose substrates (benzalkonium, ethidium, acriflavine, TPP) are organic cations. Reason: Correct but general. GO:0140968 polyspecific organic cation:proton antiporter activity (is_a antiporter activity) matches the measured H+ coupling and substrate range. Proposed replacements: polyspecific organic cation:proton antiporter activity Supporting Evidence: PMID:14679249 Addition of benzalkonium chloride to the assay mixture caused efflux of H + , indicating that H + -benzalkonium chloride antiport took place. PMID:14679249 Deletion of the pmpM gene from the chromosome of PMX52 resulted in a decrease in the MICs of benzalkonium chloride, ethidium bromide, acriflavine, and TPPCl. |
| GO:0016020 membrane | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA from the MATE-family root PTN000129144 (19 seeds across bacteria, plants and mammals, including PmpM itself). Reason: True and soundly propagated, but plasma membrane (is_a membrane), accepted in this review, entails it. Supporting Evidence: PMID:14679249 Addition of benzalkonium chloride to the assay mixture caused efflux of H + , indicating that H + -benzalkonium chloride antiport took place. |
| GO:0016020 membrane | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the MATE family. Reason: Entailed by the accepted plasma membrane rows. Supporting Evidence: PMID:14679249 Addition of benzalkonium chloride to the assay mixture caused efflux of H + , indicating that H + -benzalkonium chloride antiport took place. |
| GO:0042908 xenobiotic transport | IEA GO_REF:0000108 | MODIFY | Summary: Logical inference from xenobiotic transmembrane transporter activity. Reason: Correct but general. PmpM exports antimicrobials out of the cell across the cytoplasmic membrane, so GO:1990961 xenobiotic detoxification by transmembrane export across the plasma membrane (is_a xenobiotic export from cell, is_a xenobiotic transport) is the precise process. Proposed replacements: xenobiotic detoxification by transmembrane export across the plasma membrane Supporting Evidence: PMID:14679249 Deletion of the pmpM gene from the chromosome of PMX52 resulted in a decrease in the MICs of benzalkonium chloride, ethidium bromide, acriflavine, and TPPCl. |
| GO:0042910 xenobiotic transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000129414 (NorM/MdtK subfamily), seeded by E. coli MdtK. PmpM's own efflux data agree. Reason: Core; PmpM transports antimicrobial xenobiotics across the membrane. Supporting Evidence: PMID:14679249 Addition of benzalkonium chloride to the assay mixture caused efflux of H + , indicating that H + -benzalkonium chloride antiport took place. |
| GO:0042910 xenobiotic transmembrane transporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the MATE family. Reason: Consistent with the direct transport data. Supporting Evidence: PMID:14679249 Addition of benzalkonium chloride to the assay mixture caused efflux of H + , indicating that H + -benzalkonium chloride antiport took place. |
| GO:0046677 response to antibiotic | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from PTN000129414 seeded by MdtK. PmpM deletion lowers MICs of several antimicrobials. Reason: True resistance phenotype of an efflux pump; non-core relative to the export function, as on the PA4218 and PA3677 reviews. Supporting Evidence: PMID:14679249 Deletion of the pmpM gene from the chromosome of PMX52 resulted in a decrease in the MICs of benzalkonium chloride, ethidium bromide, acriflavine, and TPPCl. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the MATE family. Reason: True but entailed by GO:1990961, asserted in core_functions (is_a export across plasma membrane, is_a transmembrane transport). Supporting Evidence: PMID:14679249 Addition of benzalkonium chloride to the assay mixture caused efflux of H + , indicating that H + -benzalkonium chloride antiport took place. |
| GO:0098567 periplasmic side of plasma membrane | IDA PMID:14679249 An H(+)-coupled multidrug efflux pump, PmpM, a member of the... | REMOVE | Summary: PseudoCAP IDA and a seed of the PTN000129144 membrane IBD. The paper contains no sidedness, topology or localization experiment; the only membrane data are transport assays in everted E. coli membrane vesicles. PmpM is a 12-helix integral membrane protein spanning both leaflets. Reason: The term is not supported by the paper and misdescribes a polytopic transporter as located on one face of the membrane. Seed verdict WRONG; the membrane IBD stands on the plasma membrane row and 18 other seeds. Supporting Evidence: PMID:14679249 Addition of benzalkonium chloride to the assay mixture caused efflux of H + , indicating that H + -benzalkonium chloride antiport took place. |
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Download this section (compressed HTML)Q: Which residues of PmpM set H+ rather than Na+ coupling, given that its closest characterized relatives (NorM, YdhE) are Na+-coupled?
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