ttgC encodes a 484-aa outer membrane lipoprotein of the outer membrane factor (OMF) family that serves as the outer membrane channel of RND-type efflux systems in Pseudomonas putida KT2440. UniProt and comparative genomics place it in the TtgABC efflux pump, while genetic and regulatory studies in KT2440 link ttgABC/TtgC to phenol responses, stress phenotypes, and antibiotic-resistant regulatory mutants. More recent work indicates that TtgC can also be shared by the ParXY/TtgC efflux system in multidrug-resistant P. putida isolates. The strongest conservative functional summary is therefore an outer membrane efflux transporter component contributing to transmembrane export of toxic compounds, including antibiotics and aromatic solvent-related stresses, with exact substrate preference depending on regulatory and pump context.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0009279 cell outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Accept. TtgC is an OMF-family outer membrane lipoprotein, and UniProt explicitly places it in the cell outer membrane. This is the most specific supported localization among the current GOA terms. Reason: The reviewed UniProt entry describes TtgC as a probable efflux pump outer membrane protein with cell-outer-membrane localization and lipid anchoring, which matches the expected architecture of tripartite RND efflux systems. Supporting Evidence: file:PSEPK/ttgC/ttgC-uniprot.txt Cell outer membrane {ECO:0000305}; Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303}. |
| GO:0015562 efflux transmembrane transporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: Accept. The best-supported molecular function for TtgC is participation in efflux transport across the cell envelope as the outer membrane channel of RND transporter systems. Reason: Multiple lines of evidence support efflux function in KT2440. TtgABC is described as the major multidrug efflux pump in KT2440, ttgC abundance rises during phenol stress, and TtgC can also partner with ParXY in multidrug-resistant P. putida strains. Although the exact substrate range is context dependent, efflux transporter activity is the correct core molecular-function summary. Supporting Evidence: file:PSEPK/ttgC/ttgC-uniprot.txt Probable outer membrane component of the TtgABC efflux pump with unknown specificity. PMID:24907323 ttgA, ttgB, and ttgC, which code for the major multidrug efflux pump TtgABC in P. putida KT2440 PMID:32840000 TtgABC and ParXY/TtgC are both under the positive control of a two-component system, PpeRS file:PSEPK/ttgC/ttgC-deep-research-falcon.md The gene ttgC in Pseudomonas putida KT2440 encodes the outer membrane factor (OMF) of the tripartite RND efflux pump TtgABC |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: This annotation is too generic. TtgC localizes specifically to the cell outer membrane, so the broader parent term membrane adds little value. Reason: GO:0016020 is a high-level parent term that is superseded here by the more informative and better supported GO:0009279 cell outer membrane. Supporting Evidence: file:PSEPK/ttgC/ttgC-uniprot.txt Cell outer membrane {ECO:0000305}; Lipid-anchor {ECO:0000255|PROSITE-ProRule:PRU00303}. |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: This parent transporter term is directionally correct but redundant once the more specific efflux transporter activity annotation is retained. Reason: The available evidence specifically supports export/efflux rather than generic transmembrane transporter activity, so GO:0015562 is the more informative annotation. Supporting Evidence: PMID:24907323 major multidrug efflux pump TtgABC |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: Accept. Even though the substrate spectrum is broader than a single antibiotic or solvent term, TtgC is clearly involved in transmembrane export processes mediated by RND efflux systems. Reason: KT2440 data connect ttgC/TtgABC to phenol adaptation, antibiotic resistance, and multidrug efflux. The broad biological-process term is conservative but justified until a single substrate-specific process can be supported without over-annotation. Supporting Evidence: file:PSEPK/ttgC/ttgC-deep-research-falcon.md In a KT2440-isogenic background (PaW85), genetic inactivation of **ttgABC/ttgC** produced an initially counterintuitive phenotype: disruption of the pump **enhanced phenol tolerance** PMID:24907323 demonstrated the involvement of efflux pump TtgABC in the stress resistance and biofilm formation phenotypes of the ECF-10 mutant strain file:PSEPK/ttgC/ttgC-deep-research-falcon.md In KT2440 MDR evolution/selection experiments, **PpeRS** is described as a positive regulator controlling **both TtgABC and ParXY/TtgC** file:PSEPK/ttgC/ttgC-deep-research-falcon.md the primary biological role of the TtgABC/TtgC system is detoxification and intrinsic resistance against multiple compound classes, including antibiotics, aromatic hydrocarbons/solvents, and specialized metabolites |
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Download this section (compressed HTML)Q: What are the physiologically dominant substrates of TtgC under native KT2440 growth conditions: antibiotics, aromatic solvents, phenolic compounds, or a broader toxic-compound spectrum?
Suggested experts: Ramos JL, Overhage J, Jeannot K
Q: Under which regulatory and environmental conditions does TtgC function with TtgAB versus the ParXY pump in P. putida KT2440 and related strains?
Suggested experts: Overhage J, Jeannot K
Experiment: Construct clean ttgC, ttgABC, and parXY mutants plus defined complementation strains and quantify susceptibility to phenol, toluene, quinolones, beta-lactams, chloramphenicol, and aminoglycosides.
Hypothesis: TtgC is required for efficient export of multiple toxic compounds, but the relative contribution of TtgABC versus ParXY/TtgC depends on the stress condition and regulatory state.
Experiment: Measure intracellular accumulation and efflux kinetics of fluorescent or radiolabeled antibiotics and aromatic compounds in wild type, ttgR mutants, ppeRS-activated backgrounds, and ttgC knockouts.
Hypothesis: Derepression of ttgABC or coordinated activation of ttgABC and parXY will lower intracellular substrate accumulation in a TtgC-dependent manner.
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