CueR (PA4778) is the MerR-family copper(I)-sensing transcriptional regulator of Pseudomonas aeruginosa. It has an N-terminal winged helix-turn-helix DNA-binding domain and a C-terminal metal-binding region, forms dimers and tetramers, and is metallated by Cu(+) handed over from the CopZ1 and CopZ2 chaperones. Copper-loaded CueR binds directly to the promoters of its targets and activates five transcriptional units (flcABCDE, copZ1, mexPQ-opmE, copZ2 and cueA), which together protect the cell against copper toxicity; cueR mutants are copper sensitive. Under copper-rich conditions it also represses the H2 type VI secretion system and the azurin/OprC copper uptake genes. cueR itself is activated by the quorum-sensing regulator LasR, linking copper homeostasis to the quorum response.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003677 DNA binding | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO from the MerR HTH domain. Correct but general - CueR binds specific promoter operators of its target genes. Reason: Refine to transcription cis-regulatory region binding (GO:0000976), a descendant of DNA binding, supported by direct promoter-binding data. Proposed replacements: transcription cis-regulatory region binding Supporting Evidence: file:PSEAE/cueR/cueR-uniprot.txt Acts by binding directly to the promoter region of its targets |
| GO:0003700 DNA-binding transcription factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the PTN001575588 IBD (MerR family node, seeded by E. coli CueR, ZntR, MlrA, BluR, Xanthomonas SoxR and P. aeruginosa BrlR). CueR is a bona fide DNA-binding transcription factor with direct promoter binding shown for this protein. Reason: Sound node assertion. Not refined to the activator term because CueR both activates and represses targets, so the general TF activity is the honest level. Supporting Evidence: PMID:20233934 show that the protein directly binds to and activates five promoters |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping (CueR and MerR-family signatures), agreeing with the IBA row and the experimental data. Reason: Consistent with the accepted IBA and with direct evidence. |
| GO:0005507 copper ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the CueR family signature. CueR is a Cu(+) metallosensor metallated by CopZ chaperones; UniProt records two metal-binding residues. Reason: Copper binding is the sensory input that activates CueR and is supported by experimental metallation data cited in UniProt. Supporting Evidence: file:PSEAE/cueR/cueR-uniprot.txt Activation of CueR occurs via direct Cu(+) transfer from the CopZ metal chaperones |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping; a soluble cytoplasmic regulator. Reason: Correct location for a soluble bacterial transcription factor. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the MerR HTH domain. True, but positive regulation of DNA-templated transcription (GO:0045893), accepted above, is_a this term. Reason: Entailed by the accepted GO:0045893 rows. |
| GO:0045893 positive regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the PTN001249777 IBD (CueR/ZntR clade), seeded by E. coli CueR (P0A9G4), E. coli ZntR (P0ACS5) and this gene's PseudoCAP row; the self-appearance in WITH/FROM is expected. MerR-type metal sensors of this clade are classical activators. Reason: Core process, directly shown for PAO1 CueR and well founded at the node. Supporting Evidence: PMID:20233934 show that the protein directly binds to and activates five promoters |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the CueR signature (IPR011789), same claim as the IBA. Reason: Consistent with direct evidence. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:20233934 Quorum-sensing regulation of a copper toxicity system in Pse... | ACCEPT | Summary: PseudoCAP row and the seed of the PTN001575588 (GO:0006355) and PTN001249777 (GO:0045893) IBDs. The paper shows direct promoter binding and activation by PA4778 and uses gene disruptions, so the positive regulation claim is about CueR's own activity, not an indirect phenotype. Reason: Sound seed; core function of the gene. Supporting Evidence: PMID:20233934 We also identify a putative PA4778 binding motif and show that the protein directly binds to and activates five promoters controlling the expression of 11 genes |
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Download this section (compressed HTML)Q: Does P. aeruginosa CueR repress the H2-T6SS and azu/oprC genes by the same DNA-distortion mechanism by which it activates the copper-resistance promoters, or through a different operator architecture?
Experiment: In vitro transcription with purified apo- and Cu(+)-CueR on the cueA and H2-T6SS promoters, to separate direct activation from direct repression and to assign the DNA-binding transcription activator and repressor activities individually.
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