PA2127 (cgrA) encodes CgrA, a 408-residue cytoplasmic protein of the adenine nucleotide alpha-hydrolase superfamily with a phosphoadenosine phosphosulfate (PAPS) reductase-like domain and a DUF3440 region. It is one of the cgrABC genes, which lie immediately upstream of the cupA fimbrial cluster. CgrA, CgrB and CgrC are unusual positive coregulators required for phase-variable expression of the cupA fimbrial genes, which support biofilm formation on abiotic surfaces. cgr expression is repressed by the H-NS-like MvaT and induced by anaerobiosis through the oxygen-sensing regulator Anr. CgrA binds CgrC directly, and this interaction is required for cupA expression; CgrA itself has no DNA-binding motif and was not detected at the cupA promoter, so it is thought to be recruited there by CgrC. No enzymatic activity has been shown for its PAPS reductase-like domain.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO from the PAPS reductase domain (IPR002500). CgrA is a PAPS reductase-like member of the adenine nucleotide alpha-hydrolase superfamily, but no catalytic activity has been reported and it acts as a transcriptional coregulator. Reason: A domain-based guess with no assay; the protein's known role is regulatory, and whether the PAPS reductase-like fold retains catalysis is unknown. Supporting Evidence: PMID:21926232 CgrA is predicted to be a member of the adenine nucleotide Ξ±-hydrolase superfamily of proteins and contains a putative PAPS reductase domain |
| GO:0005515 protein binding | IPI PMID:21926232 The CgrA and CgrC proteins form a complex that positively re... | REMOVE | Summary: Bacterial two-hybrid interaction between CgrA and CgrC (McManus and Dove 2011, full text read). Reason: Bare protein binding is uninformative (protein-binding policy). The CgrA-CgrC interaction is real and required for cupA expression; it is captured by the coregulator role below. Removal does not dispute the interaction. Supporting Evidence: PMID:21926232 Here, we show that CgrA and CgrC interact with one another directly. |
| GO:0071453 cellular response to oxygen levels | IBA GO_REF:0000033 | MODIFY | Summary: IBA from PTN000764275 (12 leaf IBAs, 5 taxa). Its only seeds are CgrA and CgrC themselves, both by PseudoCAP IEP. Reason: For PA2127 itself the claim holds at the expression level (the cgr genes are induced by anaerobiosis via Anr), and the stimulus is anoxia, so GO:0071454 cellular response to anoxia is the precise term, as for the IEP rows. The IBD itself is unsound for the other leaves - it propagates a species-specific expression response - so the propagated claim should be withdrawn at the node. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000764275 Β· PTN000764275 SOURCE WEAK OR INFERRED IBD seeded only by two IEP rows from one species; expression evidence is not an inheritable function. UniProtKB:Q9I1Y8 Β· PA2127 (CgrA) (self) SUPPORTS SOURCE BUT NOT TARGET PseudoCAP IEP (PMID:17890313, PMID:20553552); expression induction by anaerobiosis via Anr. UniProtKB:Q9I1Y9 Β· PA2126 (CgrC) SUPPORTS SOURCE BUT NOT TARGET PseudoCAP IEP (PMID:17890313, PMID:20553552); expression induction by anaerobiosis via Anr. Proposed replacements: cellular response to anoxia Supporting Evidence: PMID:17890313 positively controlled by Anr and anaerobiosis |
| GO:0071453 cellular response to oxygen levels | IEP PMID:17890313 Local and global regulators linking anaerobiosis to cupA fim... | MODIFY | Summary: PseudoCAP seed row. The abstract states that cgr expression is positively controlled by Anr and by anaerobiosis, and that the cgr genes are needed for anaerobic cupA expression. Reason: Seed verdict SOUND as an expression (IEP) annotation; the stimulus is anaerobiosis, so GO:0071454 cellular response to anoxia (is_a GO:0071453) is the precise term. Proposed replacements: cellular response to anoxia Supporting Evidence: PMID:17890313 positively controlled by Anr and anaerobiosis PMID:17890313 the cgr genes are essential for this expression |
| GO:0071453 cellular response to oxygen levels | IEP PMID:20553552 Anaerobic adaptation in Pseudomonas aeruginosa: definition o... | MODIFY | Summary: PseudoCAP seed row. Trunk et al. 2010 (abstract only) defined the Anr and Dnr regulons by transcriptomics after oxygen depletion; the abstract does not name the cgr genes, so their induction in this dataset could not be checked. Reason: Consistent with the PMID:17890313 row, which the abstract there supports directly; the stimulus is oxygen depletion, so GO:0071454 is the precise term. Seed verdict for this paper UNVERIFIABLE; no defect. Proposed replacements: cellular response to anoxia Supporting Evidence: PMID:20553552 Comprehensive transcriptome and bioinformatics analyses in combination with a limited proteome analyses were used for the investigation of the P. aeruginosa response to an immediate oxygen depletion |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:21926232 The CgrA and CgrC proteins form a complex that positively re... | NEW | Summary: Proposed. All three cgr genes are required for phase-variable cupA expression; a CgrC mutant that cannot bind CgrA fails to restore cupA expression, and CgrC associates with the cupA promoter (ChIP). Reason: CgrA is a coregulator recruited to the cupA promoter by CgrC; the CgrA-CgrC interaction is required for cupA expression. The molecular mechanism is unknown, so no MF term is proposed. Supporting Evidence: PMID:21926232 interaction between CgrA and CgrC is required for the phase-variable expression of the cupA fimbrial genes PMID:21926232 we propose that one role of the interaction between CgrC and CgrA is to recruit CgrA to the cupA promoter region |
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Download this section (compressed HTML)Q: Does the PAPS reductase-like domain of CgrA retain any catalytic activity (for example ATP pyrophosphatase or sulfonucleotide reduction), and is that activity needed for cupA activation?
Q: Are CgrA/CgrC orthologs in other bacteria oxygen-regulated, or is the Anr control of cgr expression specific to P. aeruginosa? This decides whether any oxygen-response term can be inherited at PTN000764275.
Experiment: Purify CgrA (alone and with CgrC) and assay ATP hydrolysis and PAPS/APS reduction; test catalytic-site point mutants for complementation of cupA expression in a cgrA mutant.
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