MexT (PA2492, NfxC) is a LysR-type transcriptional activator of Pseudomonas aeruginosa. It binds nod-box-like sites in the mexEF-oprN promoter and activates the MexEF-OprN multidrug efflux pump, and directly activates a small regulon that includes mexS (qrh), whose product in turn modulates MexT. Full-length MexT is a homotetramer with an N-terminal winged-helix DNA-binding domain and a C-terminal regulatory domain with a putative ligand pocket. Through MexEF-OprN, which exports quinolone antibiotics and quorum-sensing quinolones, MexT affects antibiotic resistance, the quorum-sensing hierarchy and the production of virulence factors; with MexS it also represses the type III secretion system. mexT is frequently mutated in laboratory sublines and in clinical isolates.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN001248361, seeded by S. Typhimurium LeuO (CollecTF IPI) and this gene's own rows (expected self-appearance). Reason: Consistent with direct promoter binding by MexT. Supporting Evidence: PMID:20727012 The mexT-proximal nod box was identified as the MexT-binding site by gel-shift assays using purified MexT. |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:31722511 Crystal Structure of the Regulatory Domain of MexT, a Transc... | ACCEPT | Summary: DNase I footprinting of full-length MexT on the mexEF-oprN promoter. Reason: Direct binding evidence; core. Supporting Evidence: PMID:31722511 A DNase I footprinting assay of full-length MexT identified two MexT-binding sequence in the mexEF oprN promoter. |
| GO:0000976 transcription cis-regulatory region binding | IMP PMID:19846594 Transcriptome profiling defines a novel regulon modulated by... | ACCEPT | Summary: CollecTF row; motif mutagenesis and EMSA on the MexT regulon. Reason: Core; consistent with the IDA row. Supporting Evidence: PMID:19846594 Thus, a novel regulon directly modulated by MexT, that includes but is independent of mexEF-oprN, has been identified. |
| GO:0000976 transcription cis-regulatory region binding | IMP PMID:20727012 Transcriptional regulation of the mexEF-oprN multidrug efflu... | ACCEPT | Summary: CollecTF row; EMSA with purified MexT and promoter deletions. Reason: Core; direct binding to the mexE promoter. Supporting Evidence: PMID:20727012 The mexT-proximal nod box was identified as the MexT-binding site by gel-shift assays using purified MexT. |
| GO:0001216 DNA-binding transcription activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN001248361, seeded by S. Typhimurium LeuO and MexT. Reason: Core activity of MexT. Supporting Evidence: PMID:19846594 Thus, a novel regulon directly modulated by MexT, that includes but is independent of mexEF-oprN, has been identified. |
| GO:0001216 DNA-binding transcription activator activity | IMP PMID:19846594 Transcriptome profiling defines a novel regulon modulated by... | ACCEPT | Summary: CollecTF row; MexT binds and activates its regulon promoters. Reason: Core activity. Supporting Evidence: PMID:19846594 Thus, a novel regulon directly modulated by MexT, that includes but is independent of mexEF-oprN, has been identified. |
| GO:0001216 DNA-binding transcription activator activity | IMP PMID:20727012 Transcriptional regulation of the mexEF-oprN multidrug efflu... | ACCEPT | Summary: CollecTF row; MexT binds the mexE promoter and is required for its expression. Reason: Core activity. Supporting Evidence: PMID:20727012 The mexT-proximal nod box was identified as the MexT-binding site by gel-shift assays using purified MexT. |
| GO:0001216 DNA-binding transcription activator activity | IMP PMID:39708318 Mutations in mexT bypass the stringent response dependency o... | ACCEPT | Summary: UniProt row; mexT mutant transcriptomics. Reason: Consistent with the direct-binding rows. Supporting Evidence: PMID:39708318 However, MexT is an activator of mexEF-oprN expression |
| GO:0001217 DNA-binding transcription repressor activity | IMP PMID:41128522 Modulation of the Pseudomonas aeruginosa quorum sensing casc... | MARK AS OVER ANNOTATED | Summary: UniProt row from the increased pqsE expression of the mexT deletion. The full text attributes this to MexEF-OprN (quinolone export), not to MexT binding the pqs promoter. Reason: No direct DNA-binding repression is shown; the repression is downstream of MexT activating mexEF-oprN. Curators read the full text, so this is not removed, but it over-states MexT's own activity. Supporting Evidence: PMID:41128522 we hypothesized that constitutive MexT activity induces mexEF-oprN expression, leading to the repression of PQS QS, delayed pqsE expression, and delayed RhlR activation. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the LysR HTH domain. Reason: Entailed by the accepted GO:0001216 (is_a GO:0003700). |
| GO:0005667 transcription regulator complex | IDA PMID:31722511 Crystal Structure of the Regulatory Domain of MexT, a Transc... | KEEP AS NON CORE | Summary: UniProt row; full-length MexT is a homotetramer by SEC-MALS. Reason: True for a homotetrameric LysR regulator, but it records oligomerisation rather than a distinct complex. Supporting Evidence: PMID:31722511 FL MexT and MexT RD were homotetrameric and homodimeric in solution, respectively, as determined using SEC-MALS |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA from PTN001248361, seeded by E. coli LeuO (IMP), S. Typhimurium LeuO (CollecTF) and this gene's PseudoCAP row. Sound at the node. Reason: True, but entailed by the accepted GO:0045893. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the LysR HTH domain. Reason: Entailed by the accepted GO:0045893. |
| GO:0009372 quorum sensing | IMP PMID:39708318 Mutations in mexT bypass the stringent response dependency o... | KEEP AS NON CORE | Summary: UniProt row. mexT mutants reactivate QS-dependent virulence; MexT shapes QS signalling mostly through MexEF-OprN export of quinolones. Reason: A genuine but indirect, pump-mediated influence on QS. Supporting Evidence: PMID:41128522 we hypothesized that constitutive MexT activity induces mexEF-oprN expression, leading to the repression of PQS QS, delayed pqsE expression, and delayed RhlR activation. |
| GO:0010629 negative regulation of gene expression | IMP PMID:9044268 Characterization of MexE-MexF-OprN, a positively regulated m... | KEEP AS NON CORE | Summary: UniProt row, probably for the coregulated decrease of the OprD porin in nfxC-type (MexT-active) strains. Reason: Plausible indirect effect (UniProt calls the OprD down-regulation probable and post-transcriptional); not the core activity. |
| GO:0032993 protein-DNA complex | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from PTN001248361 recording the regulator-promoter complex. Reason: True (EMSA complexes) but adds little beyond the cis-regulatory binding rows. |
| GO:0032993 protein-DNA complex | IMP PMID:19846594 Transcriptome profiling defines a novel regulon modulated by... | KEEP AS NON CORE | Summary: CollecTF standard row. Reason: True but adds little beyond GO:0000976. |
| GO:0032993 protein-DNA complex | IMP PMID:20727012 Transcriptional regulation of the mexEF-oprN multidrug efflu... | KEEP AS NON CORE | Summary: CollecTF standard row. Reason: True but adds little beyond GO:0000976. |
| GO:0045861 negative regulation of proteolysis | IMP PMID:21075931 MexT regulates the type III secretion system through MexS an... | REMOVE | Summary: PseudoCAP row. The PAO1 mexT mutant produces more elastase; MexT is a transcription factor and does not act on protein hydrolysis. Reason: Increased protease output in a regulator mutant is an indirect phenotype, not regulation of proteolysis. The transcriptional role is captured by the accepted regulation-of-transcription rows. Supporting Evidence: PMID:21075931 the mexS and mexT mutants of PAO1 shared the same phenotype of increased elastase and pyocyanin production compared to that in wild-type PAO1 |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:41128522 Modulation of the Pseudomonas aeruginosa quorum sensing casc... | KEEP AS NON CORE | Summary: UniProt row; pqsE and other genes rise in the mexT deletion, largely through MexEF-OprN. Reason: True in the indirect sense; MexT's direct activity is activation. Supporting Evidence: PMID:41128522 we hypothesized that constitutive MexT activity induces mexEF-oprN expression, leading to the repression of PQS QS, delayed pqsE expression, and delayed RhlR activation. |
| GO:0045893 positive regulation of DNA-templated transcription | EXP PMID:19846594 Transcriptome profiling defines a novel regulon modulated by... | ACCEPT | Summary: CollecTF row; MexT directly activates its regulon. Reason: Core process. Supporting Evidence: PMID:19846594 Thus, a novel regulon directly modulated by MexT, that includes but is independent of mexEF-oprN, has been identified. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:10515918 Characterization of MexT, the regulator of the MexE-MexF-Opr... | ACCEPT | Summary: PseudoCAP seed row for PTN001248361. Reporter fusions show MexT activates mexE and qrh transcription. Seed verdict SOUND. Reason: Core process; later shown to be direct. Supporting Evidence: PMID:10515918 Expression of a qrh::lacZ fusion was also found to be activated by MexT. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:39708318 Mutations in mexT bypass the stringent response dependency o... | ACCEPT | Summary: UniProt row from mexT mutant transcriptomics. Reason: Consistent with the other rows. Supporting Evidence: PMID:39708318 However, MexT is an activator of mexEF-oprN expression |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:9044268 Characterization of MexE-MexF-OprN, a positively regulated m... | ACCEPT | Summary: UniProt row; the upstream LysR gene positively regulates mexEF-oprN. Reason: Consistent with the other rows. Supporting Evidence: PMID:9044268 Expression of the mexEF-oprN operon was shown to be positively regulated by a protein encoded on a 1.5 kb DNA fragment located upstream of mexE |
| GO:0046677 response to antibiotic | IMP PMID:39708318 Mutations in mexT bypass the stringent response dependency o... | MARK AS OVER ANNOTATED | Summary: UniProt row from altered aminoglycoside, colistin and ciprofloxacin susceptibility of mexT mutants. Reason: Changed resistance in a regulator mutant is not a response to antibiotic; MexT is not shown to be triggered by the antibiotics. Supporting Evidence: PMID:39708318 leads to elevated aminoglycoside resistance |
| GO:0046677 response to antibiotic | IMP PMID:9044268 Characterization of MexE-MexF-OprN, a positively regulated m... | MARK AS OVER ANNOTATED | Summary: UniProt row from the multidrug phenotype conferred by the regulator plasmid. Reason: Resistance via pump expression, not a response to the antibiotic. Supporting Evidence: PMID:9044268 Expression of the mexEF-oprN operon was shown to be positively regulated by a protein encoded on a 1.5 kb DNA fragment located upstream of mexE |
| GO:0050709 negative regulation of protein secretion | IMP PMID:21075931 MexT regulates the type III secretion system through MexS an... | KEEP AS NON CORE | Summary: PseudoCAP row. A PAO1 mexT mutant secretes much more ExoS; MexT represses the T3SS through MexS. Reason: An indirect but genuine regulatory effect on T3SS-dependent secretion; peripheral to the core activator function. Supporting Evidence: PMID:21075931 However, a mexT mutant of PAO1 (PAO1 mexT ::Gm) resulted in much higher ExoS secretion than that of its parental strain PAO1 |
| GO:1900377 negative regulation of secondary metabolite biosynthetic process | IMP PMID:21075931 MexT regulates the type III secretion system through MexS an... | MODIFY | Summary: PseudoCAP row. The PAO1 mexT mutant makes more pyocyanin. Reason: Correct but general; the secondary metabolite is pyocyanin, a phenazine. No negative regulation of pyocyanine biosynthesis term exists, so the specific supported term is GO:1900981. Non-core. Proposed replacements: negative regulation of phenazine biosynthetic process Supporting Evidence: PMID:21075931 the mexS and mexT mutants of PAO1 shared the same phenotype of increased elastase and pyocyanin production compared to that in wild-type PAO1 |
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