NalC (PA3721) is a TetR/AcrR-family transcriptional repressor of Pseudomonas aeruginosa that controls the divergently transcribed PA3720-armR operon. NalC binds an inverted repeat overlapping the PA3720-armR promoter, and phenolic compounds such as pentachlorophenol release it from the DNA. ArmR (PA3719), a 53-residue anti-repressor, binds the MexR repressor and relieves MexR repression of the mexAB-oprM multidrug efflux operon. Loss-of-function nalC mutations (nalC-type multidrug-resistant mutants) therefore raise ArmR levels and cause moderate MexAB-OprM overexpression and multidrug resistance, so NalC controls efflux indirectly, through a repressor cascade.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IBA GO_REF:0000033 | MODIFY | Summary: IBA from the PTN004738546 IBD (7 seeds). nalC sits inside this TetR clade and is itself a seed, which is expected, not circular. nalC binds an inverted-repeat operator in its target promoter. Reason: Correct and appropriate for the node, but binding to a defined inverted-repeat operator supports the child GO:0000987 cis-regulatory region sequence-specific DNA binding for this gene (the same refinement used for mexZ, which shares the node). The generic term stays right for the node. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN004738546 · PTN004738546 SUPPORTS TRANSFER TetR-family PAINT node (411 leaf IBAs, 33 taxa). Its IBDs rest on 19 seeds for GO:0006355, 7 for GO:0000976 and 7 for GO:0003700, including E. coli AcrR (P0ACS9, IDA operator binding and DNA-binding TF activity), RutR (P0ACU2), Vibrio VC_1746 (Q9KR96) and M. tuberculosis KstR, Mce3R and EthR. The generic node terms suit a TetR clade and stand without any single seed; node-level verdict recorded in the nfxB notes. UniProtKB:Q9HXS0 · nalC (self; experimental seed) SUPPORTS TRANSFER Expected self-seed reflecting the target's own experimental evidence; not circular. Proposed replacements: cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:22393435 The NalC binding site was localized to an inverted repeat (IR) sequence upstream of PA3720-armR PMID:22393435 the repressor's binding to PA3720-armR promoter-containing DNA as seen in electromobility shift assays (EMSAs) being obviated in the presence of this agent |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:22393435 Pentachlorophenol induction of the Pseudomonas aeruginosa me... | MODIFY | Summary: PseudoCAP IDA and one of the 7 seeds of the PTN004738546 GO:0000976 IBD. EMSA with purified NalC on the PA3720-armR promoter region; the binding site was localized to an inverted repeat. Seed verdict SOUND (full text read). Reason: Sound but under-specific: binding to a defined inverted repeat supports GO:0000987. GO:0000987 is a child of GO:0000976, so the IBD stays supported. Proposed replacements: cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:22393435 The NalC binding site was localized to an inverted repeat (IR) sequence upstream of PA3720-armR PMID:22393435 the repressor's binding to PA3720-armR promoter-containing DNA as seen in electromobility shift assays (EMSAs) being obviated in the presence of this agent |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: InterPro/UniRule mapping from the TetR HTH (TetR_N) domain. True. Reason: DNA binding is correct but general; nalC binds a defined operator, which supports GO:0000987. Proposed replacements: cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:22393435 The NalC binding site was localized to an inverted repeat (IR) sequence upstream of PA3720-armR PMID:22393435 the repressor's binding to PA3720-armR promoter-containing DNA as seen in electromobility shift assays (EMSAs) being obviated in the presence of this agent |
| GO:0003700 DNA-binding transcription factor activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA from the PTN004738546 IBD (7 seeds). nalC is a DNA-binding TetR-family repressor. Reason: Correct but general. The gene-level evidence (operator binding plus derepression in the mutant) supports GO:0001217 DNA-binding transcription repressor activity. The generic term remains right for the node. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN004738546 · PTN004738546 SUPPORTS TRANSFER TetR-family PAINT node (411 leaf IBAs, 33 taxa). Its IBDs rest on 19 seeds for GO:0006355, 7 for GO:0000976 and 7 for GO:0003700, including E. coli AcrR (P0ACS9, IDA operator binding and DNA-binding TF activity), RutR (P0ACU2), Vibrio VC_1746 (Q9KR96) and M. tuberculosis KstR, Mce3R and EthR. The generic node terms suit a TetR clade and stand without any single seed; node-level verdict recorded in the nfxB notes. UniProtKB:Q9HXS0 · nalC (self; experimental seed) SUPPORTS TRANSFER Expected self-seed reflecting the target's own experimental evidence; not circular. Proposed replacements: DNA-binding transcription repressor activity Supporting Evidence: PMID:22393435 The NalC binding site was localized to an inverted repeat (IR) sequence upstream of PA3720-armR PMID:22393435 the repressor's binding to PA3720-armR promoter-containing DNA as seen in electromobility shift assays (EMSAs) being obviated in the presence of this agent PMID:15387820 PA3720-PA3719, whose expression was negatively regulated by PA3721 PMID:22393435 although the mutant showed the expected increase in PA3720-armR expression compared with its wild type parent K767 |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IPR050109 TetR-like regulator) mapping. True. Reason: Correct but general; the gene-level evidence supports GO:0001217 DNA-binding transcription repressor activity. Proposed replacements: DNA-binding transcription repressor activity Supporting Evidence: PMID:22393435 The NalC binding site was localized to an inverted repeat (IR) sequence upstream of PA3720-armR PMID:22393435 the repressor's binding to PA3720-armR promoter-containing DNA as seen in electromobility shift assays (EMSAs) being obviated in the presence of this agent PMID:15387820 PA3720-PA3719, whose expression was negatively regulated by PA3721 PMID:22393435 although the mutant showed the expected increase in PA3720-armR expression compared with its wild type parent K767 |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | MODIFY | Summary: IBA from the PTN004738546 IBD (19 seeds). nalC is one of them, which is expected, not circular. The IBD stands on the other 18 seeds as well. Reason: Correct and appropriate for the node, but nalC is a repressor; GO:0045892 negative regulation of DNA-templated transcription is supported by the gene's own experimental rows. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN004738546 · PTN004738546 SUPPORTS TRANSFER TetR-family PAINT node (411 leaf IBAs, 33 taxa). Its IBDs rest on 19 seeds for GO:0006355, 7 for GO:0000976 and 7 for GO:0003700, including E. coli AcrR (P0ACS9, IDA operator binding and DNA-binding TF activity), RutR (P0ACU2), Vibrio VC_1746 (Q9KR96) and M. tuberculosis KstR, Mce3R and EthR. The generic node terms suit a TetR clade and stand without any single seed; node-level verdict recorded in the nfxB notes. UniProtKB:Q9HXS0 · nalC (self; experimental seed) SUPPORTS TRANSFER Expected self-seed reflecting the target's own experimental evidence; not circular. Proposed replacements: negative regulation of DNA-templated transcription Supporting Evidence: PMID:15387820 PA3720-PA3719, whose expression was negatively regulated by PA3721 PMID:22393435 although the mutant showed the expected increase in PA3720-armR expression compared with its wild type parent K767 |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IPR050109) mapping. True. Reason: Correct but general; nalC is shown to be a repressor, so GO:0045892 applies. Proposed replacements: negative regulation of DNA-templated transcription Supporting Evidence: PMID:15387820 PA3720-PA3719, whose expression was negatively regulated by PA3721 PMID:22393435 although the mutant showed the expected increase in PA3720-armR expression compared with its wild type parent K767 |
| GO:0032410 negative regulation of transporter activity | IMP PMID:15387820 MexAB-OprM hyperexpression in NalC-type multidrug-resistant ... | REMOVE | Summary: PseudoCAP IMP. NalC represses PA3720-PA3719; PA3719 (ArmR) affects MexAB-OprM expression. Reason: GO:0032410 is a process that reduces transporter activity. NalC represses an anti-repressor operon, and the efflux pump changes in amount, not activity, two regulatory steps downstream. Supporting Evidence: PMID:15387820 Thus, the nalC (PA3721) mutation serves only to enhance PA3720-PA3719 expression |
| GO:0034763 negative regulation of transmembrane transport | IMP PMID:15387820 MexAB-OprM hyperexpression in NalC-type multidrug-resistant ... | MARK AS OVER ANNOTATED | Summary: PseudoCAP IMP. nalC mutants overexpress MexAB-OprM through derepression of the ArmR anti-repressor. Reason: NalC's direct target is PA3720-armR. The effect on efflux runs through ArmR and MexR, a two-step cascade, so annotating NalC to regulation of transmembrane transport stretches the convention that a transcription factor is annotated to the process its targets perform. The direct repressors MexR and NalD carry this role more faithfully. Supporting Evidence: PMID:15387820 Thus, the nalC (PA3721) mutation serves only to enhance PA3720-PA3719 expression |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:22393435 Pentachlorophenol induction of the Pseudomonas aeruginosa me... | ACCEPT | Summary: PseudoCAP IMP and one of the 19 seeds of the PTN004738546 GO:0006355 IBD. The nalC mutant K1454 shows increased PA3720-armR expression, and NalC binds the PA3720-armR promoter. Seed verdict SOUND. Reason: Direct repressor of PA3720-armR; core BP. Supporting Evidence: PMID:22393435 although the mutant showed the expected increase in PA3720-armR expression compared with its wild type parent K767 PMID:22393435 the repressor's binding to PA3720-armR promoter-containing DNA as seen in electromobility shift assays (EMSAs) being obviated in the presence of this agent PMID:15387820 PA3720-PA3719, whose expression was negatively regulated by PA3721 |
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Download this section (compressed HTML)Q: What is the physiological phenolic effector of NalC, given that PCP acts only at high micromolar levels?
Experiment: Screen plant phenolics for release of NalC from the PA3720-armR operator by EMSA and measure binding affinities.
Type: ligand screening
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