PA4596, renamed EsrC (envelope stress-regulated repressor of mexCD-oprJ), is a TetR-family transcriptional repressor encoded downstream of oprJ in the nfxB-mexC-mexD-oprJ multidrug efflux locus. Purified EsrC binds a DNA fragment carrying the mexCD-oprJ promoter. Its loss has no effect on mexCD-oprJ expression in unstressed cells but raises it more than 10-fold under envelope stress, so EsrC moderates envelope stress-induced expression of the MexCD-OprJ efflux pump. esrC is itself induced by envelope stress through the AlgU sigma factor and is repressed by NfxB, the primary mexCD-oprJ repressor, and EsrC repressor activity appears to depend on NfxB. The annotated 172-residue product may lack the N-terminal part of the TetR helix-turn-helix domain because of a misassigned start codon.
The protein sequence of this entry may not correspond to a single real gene product (for example, two neighbouring genes joined into one model, or a truncated model). Read the name, features and annotations of the entry with this in mind.
WRONG START SITE SUSPECTED DOMAIN ARCHITECTUREORTHOLOG COMPARISONGENOMIC SEQUENCE
The annotated 172-aa product begins within the TetR HTH domain and has no PF00440/IPR001647 match. The reading frame stays open 93 codons upstream, the residues immediately upstream resemble TetR helix 1, and 70 of 73 UniRef50 members are 180 aa or longer. The true start is probably upstream, which would restore helix 1 of the DNA-binding domain. It does not change the GO calls.
Supported by:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the TetR-family node PTN004738546. Purified EsrC binds a DNA fragment carrying the mexCD-oprJ promoter, which is a cis-regulatory region. Reason: Consistent with the gene's own EMSA evidence. A specific binding site has not been mapped, so cis-regulatory region binding is as precise as the evidence allows. Supporting Evidence: PMID:25143244 the purified protein was able to bind to a DNA fragment carrying the mexCD-oprJ promoter region |
| GO:0003700 DNA-binding transcription factor activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA from PTN004738546. True of EsrC, which binds the mexCD-oprJ promoter and whose loss derepresses the operon under envelope stress. Reason: Correct but general. The gene-level evidence (promoter binding plus derepression in the mutant) supports the more specific child 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 node with many experimentally characterised repressors among its seeds; the generic DNA-binding transcription factor term suits the clade. The node-level verdict is recorded on the nfxB/nalC/PA3678/atuR/nalD reviews. Proposed replacements: DNA-binding transcription repressor activity Supporting Evidence: PMID:25143244 Consistent with PA4596 functioning as a mexCD-oprJ repressor, the purified protein was able to bind to a DNA fragment carrying the mexCD-oprJ promoter region |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO from the TetR-like regulator family signature. Correct for EsrC. Reason: Same claim as the IBA row; the experimental evidence supports the more specific GO:0001217 DNA-binding transcription repressor activity. Proposed replacements: DNA-binding transcription repressor activity Supporting Evidence: PMID:25143244 Consistent with PA4596 functioning as a mexCD-oprJ repressor, the purified protein was able to bind to a DNA fragment carrying the mexCD-oprJ promoter region |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | MODIFY | Summary: IBA from the PTN004738546 IBD, which has 19 seeds. PA4596 is one of them through its own PseudoCAP IDA, so its appearance in WITH/FROM is expected, not circular. The IBD stands on the other 18 seeds as well. Reason: Correct and appropriate for the node, but for this gene the evidence supports the more specific GO:0045892 negative regulation of DNA-templated transcription. The action matches the IDA row on the same term. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN004738546 · PTN004738546 SUPPORTS TRANSFER TetR-family node; 19 seeds, most experimentally characterised TetR regulators from E. coli, M. tuberculosis and P. aeruginosa. The node-level verdict is recorded on the nfxB/nalC/PA3678/atuR/nalD reviews. UniProtKB:Q9HVJ0 · PA4596 (self; PseudoCAP IDA PMID:25143244) SUPPORTS TRANSFER Expected self-seed reflecting the target's own experimental evidence. Proposed replacements: negative regulation of DNA-templated transcription Supporting Evidence: PMID:25143244 its loss under envelope stress conditions yielded a > 10-fold increase in mexCD-oprJ expression |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:25143244 EsrC, an envelope stress-regulated repressor of the mexCD-op... | MODIFY | Summary: PseudoCAP IDA and one of 19 seeds of the PTN004738546 IBD. The abstract reports EMSA binding of purified PA4596 to the mexCD-oprJ promoter and more than 10-fold derepression of mexCD-oprJ in the mutant under envelope stress. The seed is sound. Reason: Sound but under-specific. Promoter binding plus derepression in the mutant supports GO:0045892 negative regulation of DNA-templated transcription. A descendant term would still support the generic IBD, so refining it does not affect the node. Proposed replacements: negative regulation of DNA-templated transcription Supporting Evidence: PMID:25143244 its loss under envelope stress conditions yielded a > 10-fold increase in mexCD-oprJ expression PMID:25143244 the purified protein was able to bind to a DNA fragment carrying the mexCD-oprJ promoter region |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO from the TetR-like regulator family signature. Correct for EsrC. Reason: Same claim as the IBA and IDA rows; the gene-level evidence supports GO:0045892 negative regulation of DNA-templated transcription. Proposed replacements: negative regulation of DNA-templated transcription Supporting Evidence: PMID:25143244 its loss under envelope stress conditions yielded a > 10-fold increase in mexCD-oprJ expression |
Loading supporting content…
Download this section (compressed HTML)Q: Where is the true translation start of PA4596, and does the annotated 172-aa model lack TetR HTH helix 1?
Q: Does EsrC repress mexCD-oprJ by binding a site distinct from NfxB, or by forming a complex with NfxB on the promoter?
Experiment: N-terminal proteomics or ribosome profiling of PAO1 to map the PA4596 start codon, followed by DNase I footprinting of EsrC on the mexCD-oprJ promoter with and without NfxB.
Type: footprinting and start-site mapping
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)