NalD (PA3574) is a TetR-family transcriptional repressor of Pseudomonas aeruginosa that, together with MexR, controls the mexAB-oprM multidrug efflux operon. NalD binds an operator, similar to those of SmeT and TtgR, that overlaps a second, proximal mexAB-oprM promoter, and nalD mutants overexpress MexAB-OprM and are multidrug resistant (nalD-type mutants occur in clinical isolates). The phenazine pyocyanin binds NalD with micromolar affinity and releases it from the mexA promoter, linking efflux-pump induction to pyocyanin production; NalD also binds promoters of phenazine biosynthesis genes.
| 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). nalD sits inside this TetR clade and is itself a seed, which is expected, not circular. nalD 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:Q9HY46 · nalD (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:17028276 NalD binding to this region was, in fact, demonstrated PMID:40794867 Electrophoretic mobility shift assays show that PYO binding to MexR and NalD induces their dissociation from the mexA promoter |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:40794867 MexR and NalD are pyocyanin-responsive transcriptional repre... | MODIFY | Summary: UniProt IDA: EMSA of NalD on the mexA promoter, released by pyocyanin. Reason: Correct; binding to a defined operator supports the child GO:0000987, consistent with the other binding rows. Proposed replacements: cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:40794867 Electrophoretic mobility shift assays show that PYO binding to MexR and NalD induces their dissociation from the mexA promoter |
| GO:0003677 DNA binding | IDA PMID:17028276 nalD encodes a second repressor of the mexAB-oprM multidrug ... | MODIFY | Summary: PseudoCAP IDA: NalD binds a SmeT/TtgR-like operator upstream of mexAB-oprM. Reason: Correct but general; operator binding supports GO:0000987. Proposed replacements: cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:17028276 NalD binding to this region was, in fact, demonstrated |
| 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; nalD binds a defined operator, which supports GO:0000987. Proposed replacements: cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:17028276 NalD binding to this region was, in fact, demonstrated PMID:40794867 Electrophoretic mobility shift assays show that PYO binding to MexR and NalD induces their dissociation from the mexA promoter |
| GO:0003700 DNA-binding transcription factor activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA from the PTN004738546 IBD (7 seeds). nalD 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:Q9HY46 · nalD (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:17028276 NalD binding to this region was, in fact, demonstrated PMID:40794867 Electrophoretic mobility shift assays show that PYO binding to MexR and NalD induces their dissociation from the mexA promoter PMID:17028276 increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter PMID:15855496 the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | 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:17028276 NalD binding to this region was, in fact, demonstrated PMID:40794867 Electrophoretic mobility shift assays show that PYO binding to MexR and NalD induces their dissociation from the mexA promoter PMID:17028276 increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter PMID:15855496 the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | MODIFY | Summary: IBA from the PTN004738546 IBD (19 seeds). nalD 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 nalD 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:Q9HY46 · nalD (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:17028276 increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter PMID:15855496 the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IPR050109) mapping. True. Reason: Correct but general; nalD is shown to be a repressor, so GO:0045892 applies. Proposed replacements: negative regulation of DNA-templated transcription Supporting Evidence: PMID:17028276 increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter PMID:15855496 the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates |
| GO:0032410 negative regulation of transporter activity | IMP PMID:17028276 nalD encodes a second repressor of the mexAB-oprM multidrug ... | REMOVE | Summary: PseudoCAP IMP. NalD represses transcription of mexAB-oprM from a second promoter. Reason: GO:0032410 is a process that reduces transporter activity. NalD represses mexAB-oprM transcription, lowering the amount of pump, as the abstract states. The transcriptional role is captured by GO:0045892. Supporting Evidence: PMID:17028276 increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter |
| GO:0034763 negative regulation of transmembrane transport | IMP PMID:17028276 nalD encodes a second repressor of the mexAB-oprM multidrug ... | MODIFY | Summary: PseudoCAP IMP. NalD directly represses the MexAB-OprM efflux operon. Reason: Acceptable under the GO convention that a transcription factor is annotated to the process its target genes carry out. The target, MexAB-OprM, exports xenobiotics, so the descendant GO:1905700 fits (the same choice as for mexZ). Non-core. Proposed replacements: negative regulation of xenobiotic detoxification by transmembrane export across the plasma membrane Supporting Evidence: PMID:17028276 increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter PMID:15855496 the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of negative regulation of transcription. Reason: Agrees with the experimental IMP row (PMID:17028276); NalD is a direct repressor of mexAB-oprM. Supporting Evidence: PMID:17028276 increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:17028276 nalD encodes a second repressor of the mexAB-oprM multidrug ... | ACCEPT | Summary: PseudoCAP IMP and one of the 19 seeds of the PTN004738546 GO:0006355 IBD. Expression from the second mexAB-oprM promoter rises in a nalD mutant, and NalD binds that promoter. Seed verdict SOUND. Reason: Direct repressor of mexAB-oprM; core BP. Supporting Evidence: PMID:17028276 increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter PMID:17028276 NalD binding to this region was, in fact, demonstrated PMID:15855496 the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates |
| GO:0051051 negative regulation of transport | IMP PMID:15855496 Mutations in PA3574 (nalD) lead to increased MexAB-OprM expr... | MODIFY | Summary: PseudoCAP IMP. nalD mutants overexpress MexAB-OprM and the cloned nalD gene reverses multidrug resistance. Reason: Correct but general; the specific descendant GO:1905700 fits a direct repressor of a multidrug efflux pump. Non-core. Proposed replacements: negative regulation of xenobiotic detoxification by transmembrane export across the plasma membrane Supporting Evidence: PMID:15855496 the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates |
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Experiment: ChIP-seq of NalD with and without pyocyanin in PAO1, with reporter fusions to the phenazine operons.
Type: ChIP-seq
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