AlgU (AlgT, sigma-22, PA0762) is the RpoE-like (sigma-E) extracytoplasmic function sigma factor of Pseudomonas aeruginosa and its principal cell-envelope stress sigma factor. In unstressed cells the inner-membrane anti-sigma factor MucA sequesters it, helped by periplasmic MucB. Cell wall stress triggers regulated intramembrane proteolysis of MucA (AlgW, then MucP/YaeL), which releases AlgU. AlgU then binds core RNA polymerase and directs transcription from promoters with its -35 GAACTT / -10 TCtgA consensus. Its targets include its own algU-mucABCD operon, the alginate regulators algR and algZ and the algD alginate biosynthetic operon, rpoH, lipoprotein genes and envelope-repair functions. mucA mutations selected in cystic fibrosis lungs leave AlgU constitutively active, which produces the mucoid (alginate-overproducing) phenotype. In those mutants AlgU also indirectly represses flagellum synthesis (via fleQ) and contributes to biofilm formation, heat and oxidative stress resistance, and induction of the MexCD-OprJ efflux pump by membrane-damaging agents.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000345 cytosolic DNA-directed RNA polymerase complex | IDA PMID:7644517 The algT (algU) gene of Pseudomonas aeruginosa, a key regula... | ACCEPT | Summary: PseudoCAP IDA. Purified AlgT reconstituted a transcriptionally active holoenzyme with core RNA polymerase. A sigma factor is a subunit of the RNA polymerase holoenzyme. Reason: The holoenzyme is the complex in which the sigma factor acts; the reconstitution shows it. Supporting Evidence: PMID:7644517 The purified protein, in the presence of E. coli RNA polymerase core enzyme, was able to initiate transcription of an algT promoter |
| GO:0000976 transcription cis-regulatory region binding | IMP PMID:14645293 Control of Pseudomonas aeruginosa algZ expression by the alt... | MODIFY | Summary: CollecTF row; algZ transcription depends on a consensus AlgT -35/-10 promoter. Reason: Correct but general: AlgT recognises the -35/-10 core promoter elements, so GO:0001046 core promoter sequence-specific DNA binding is the precise term, as for PvdS. Proposed replacements: core promoter sequence-specific DNA binding Supporting Evidence: PMID:14645293 Most likely, AlgT is directly involved in algZ promoter recognition and transcription initiation since a promoter that is similar to a consensus AlgT promoter was identified upstream of the mapped transcription start site |
| GO:0001216 DNA-binding transcription activator activity | IMP PMID:14645293 Control of Pseudomonas aeruginosa algZ expression by the alt... | MODIFY | Summary: CollecTF row coding AlgT as a DNA-binding transcription activator. Reason: AlgT is a sigma factor; GO:0016987 is the correct sibling term. Proposed replacements: sigma factor activity Supporting Evidence: PMID:14645293 Most likely, AlgT is directly involved in algZ promoter recognition and transcription initiation since a promoter that is similar to a consensus AlgT promoter was identified upstream of the mapped transcription start site |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro region 4.2 helix-turn-helix mapping. Sigma factors contact promoter DNA (region 4.2 at -35, region 2 at -10), but they do so within the RNA polymerase holoenzyme. Reason: True, and as precise as domain-only evidence allows for a sigma subunit, whose DNA contacts are part of the holoenzyme's promoter recognition captured by GO:0016987. It is not a separate core activity. Supporting Evidence: file:PSEAE/algU/algU-uniprot.txt PF04542; Sigma70_r2 |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro mapping to DNA-binding transcription factor activity. In current GO, GO:0016987 sigma factor activity is_a GO:0003700, so this term is entailed by the sigma factor activity accepted in this review. Reason: True but uninformative; GO:0016987, accepted here, entails it. Supporting Evidence: file:PSEAE/algU/algU-uniprot.txt PF04542; Sigma70_r2 |
| GO:0006352 DNA-templated transcription initiation | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro sigma-70 mapping to transcription initiation, the step at which sigma factors act. Reason: Sigma factors take part in initiation itself (promoter recognition and open complex formation); core process. Supporting Evidence: PMID:19730690 Sigma factors are essential subunits of prokaryotic RNA polymerase, they are involved in promoter recognition and transcription initiation file:PSEAE/algU/algU-uniprot.txt PF04542; Sigma70_r2 |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | MODIFY | Summary: IBA from the PAINT IBD on PTN002455017 (8 seeds, including PvdS and AlgU). Regulation of transcription is true of every ECF sigma factor, and algU sits inside the clade. Reason: Correct but general. A sigma factor regulates transcription at the initiation step, so the specific term GO:2000142 regulation of DNA-templated transcription initiation, which the gene already carries (IEA, GO_REF:0000108), is the right gene-level term. The node-level claim itself is sound and needs no change upstream. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002455017 Β· PTN002455017 SUPPORTS TRANSFER ECF sigma factor clade node (250 leaves, 29 taxa; 8 seeds: E. coli RpoE, V. cholerae RpoE, M. tuberculosis SigC/SigH/SigL/SigM, AlgU and PvdS). The node term is appropriate for the clade and the target is a bona fide member; only the granularity for this gene differs. Proposed replacements: regulation of DNA-templated transcription initiation Supporting Evidence: PMID:19730690 Sigma factors are essential subunits of prokaryotic RNA polymerase, they are involved in promoter recognition and transcription initiation file:PSEAE/algU/algU-uniprot.txt TIGR02937; sigma70-ECF |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: InterPro sigma-70 domain mapping to regulation of transcription. Reason: Correct but general; refined to the initiation-specific term the gene already carries, consistent with the IBA row. Proposed replacements: regulation of DNA-templated transcription initiation Supporting Evidence: file:PSEAE/algU/algU-uniprot.txt PF04542; Sigma70_r2 |
| GO:0006950 response to stress | IEA GO_REF:0000117 | MODIFY | Summary: ARBA response to stress. Reason: Correct but general; the experimentally supported specific response is GO:0036460 cellular response to cell envelope stress, which the gene carries. Proposed replacements: cellular response to cell envelope stress Supporting Evidence: PMID:19226327 these data indicate that cell wall stress signals release sigma(22) by regulated intramembrane proteolysis (RIP) |
| GO:0016987 sigma factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the PAINT IBD on PTN002455017, the ECF sigma factor clade of PTHR43133 (16 seeds). algU is a member of the clade, with the ECF sigma-70 domain architecture, and is itself one of the seeds, so its own appearance in WITH/FROM is expected, not circular. Reason: Core function. The IBD is well founded on several experimentally characterised ECF sigma factors (E. coli FecI, M. tuberculosis ECF sigmas, PvdS, AlgU with in vitro transcription evidence) and the target retains the sigma-70 region 4.2 module and ECF family membership. Supporting Evidence: file:PSEAE/algU/algU-uniprot.txt TIGR02937; sigma70-ECF file:PSEAE/algU/algU-uniprot.txt PF04542; Sigma70_r2 PMID:29729420 the iron starvation Ο (PvdS, FpvI, HasI, FecI, FecI2 and others), the cell wall stress ECFΟ AlgU, SigX and SbrI, and the unorthodox ΟVreI involved in the expression of virulence |
| GO:0016987 sigma factor activity | IDA PMID:7644517 The algT (algU) gene of Pseudomonas aeruginosa, a key regula... | ACCEPT | Summary: PseudoCAP IDA and seed. Purified AlgT with E. coli core RNAP initiated transcription from the algT promoter in vitro, dependent on its -35 region: direct evidence. Reason: Seed verdict SOUND: the paper supports sigma factor activity for this gene, and the term is the core molecular function. Supporting Evidence: PMID:7644517 The purified protein, in the presence of E. coli RNA polymerase core enzyme, was able to initiate transcription of an algT promoter |
| GO:0016987 sigma factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro sigma-70 region 4 type 2 mapping to sigma factor activity. Reason: Same claim as the IBA and experimental rows, reached from domain signatures; core function. Supporting Evidence: file:PSEAE/algU/algU-uniprot.txt PF04542; Sigma70_r2 file:PSEAE/algU/algU-uniprot.txt TIGR02937; sigma70-ECF |
| GO:0032885 regulation of polysaccharide biosynthetic process | IMP PMID:14645293 Control of Pseudomonas aeruginosa algZ expression by the alt... | ACCEPT | Summary: AlgU is the sigma factor for the algD alginate biosynthetic operon and for its activators algR and algZ, so it positively regulates alginate (polysaccharide) biosynthesis. Reason: GO has no alginate-specific or positive-signed polysaccharide-biosynthesis regulation term; this is the most precise available. A defining output of AlgU. Supporting Evidence: PMID:14645293 Most likely, AlgT is directly involved in algZ promoter recognition and transcription initiation since a promoter that is similar to a consensus AlgT promoter was identified upstream of the mapped transcription start site |
| GO:0032885 regulation of polysaccharide biosynthetic process | IMP PMID:7928961 Transcriptional analysis of the Pseudomonas aeruginosa genes... | ACCEPT | Summary: AlgU is the sigma factor for the algD alginate biosynthetic operon and for its activators algR and algZ, so it positively regulates alginate (polysaccharide) biosynthesis. Reason: GO has no alginate-specific or positive-signed polysaccharide-biosynthesis regulation term; this is the most precise available. A defining output of AlgU. Supporting Evidence: PMID:7928961 Expression of algR and algD was abolished in P. aeruginosa strains containing algT::Tn501 insertions because of lack of transcription initiation at the algR and algD promoters |
| GO:0032993 protein-DNA complex | IMP PMID:14645293 Control of Pseudomonas aeruginosa algZ expression by the alt... | KEEP AS NON CORE | Summary: CollecTF row: promoter-bound AlgT holoenzyme. Reason: True but transient; a consequence of the sigma factor activity. Supporting Evidence: PMID:14645293 Most likely, AlgT is directly involved in algZ promoter recognition and transcription initiation since a promoter that is similar to a consensus AlgT promoter was identified upstream of the mapped transcription start site |
| GO:0036460 cellular response to cell envelope stress | IDA PMID:19226327 Use of cell wall stress to characterize sigma 22 (AlgT/U) ac... | ACCEPT | Summary: Cell wall stress releases sigma-22 from MucA by RIP and induces its regulon, including envelope-recovery genes. Reason: AlgU is the effector sigma factor of this stress response; core process. Supporting Evidence: PMID:19226327 these data indicate that cell wall stress signals release sigma(22) by regulated intramembrane proteolysis (RIP) |
| GO:0045893 positive regulation of DNA-templated transcription | IEP PMID:11807066 Global genomic analysis of AlgU (sigma(E))-dependent promote... | MODIFY | Summary: AlgU-dependent transcription from mapped promoters. Reason: Correct but general; the regulated step is initiation, so GO:2000144 positive regulation of DNA-templated transcription initiation. Proposed replacements: positive regulation of DNA-templated transcription initiation Supporting Evidence: PMID:11807066 A total of 10 new AlgU-dependent promoters were identified, and the corresponding mRNA start sites were mapped |
| GO:0045893 positive regulation of DNA-templated transcription | IEP PMID:14645293 Control of Pseudomonas aeruginosa algZ expression by the alt... | MODIFY | Summary: AlgU-dependent transcription from mapped promoters. Reason: Correct but general; the regulated step is initiation, so GO:2000144 positive regulation of DNA-templated transcription initiation. Proposed replacements: positive regulation of DNA-templated transcription initiation Supporting Evidence: PMID:14645293 Most likely, AlgT is directly involved in algZ promoter recognition and transcription initiation since a promoter that is similar to a consensus AlgT promoter was identified upstream of the mapped transcription start site |
| GO:0071236 cellular response to antibiotic | IMP PMID:18838593 MexCD-OprJ multidrug efflux system of Pseudomonas aeruginosa... | KEEP AS NON CORE | Summary: AlgU is required for induction of mexCD-oprJ by chlorhexidine and membrane-damaging agents. Reason: Part of AlgU's envelope-stress output; one downstream response among many. Supporting Evidence: PMID:18838593 induce expression of the mexCD-oprJ multidrug efflux operon, dependent upon the AlgU stress response sigma factor |
| GO:1900036 positive regulation of cellular response to heat | IDA PMID:9159526 Microbial pathogenesis in cystic fibrosis: co-ordinate regul... | KEEP AS NON CORE | Summary: AlgU-RNAP transcribes rpoH from its P3 promoter, induced on heat shock. Reason: Direct transcriptional input into the heat-shock response; a regulon output, not the core role. Supporting Evidence: PMID:9159526 was found to be transcribed by AIgU containing RNA polymerase from one of its promoters (P3) identified in this study |
| GO:1900189 positive regulation of cell adhesion involved in single-species biofilm formation | IMP PMID:20348252 The sigma factor AlgU plays a key role in formation of robus... | KEEP AS NON CORE | Summary: algU mutant of PAO1 is defective in attachment and robust biofilm formation, largely through indirect control of psl via ppyR. Reason: Supported by mutant and complementation data but indirect and downstream; non-core. Supporting Evidence: PMID:20348252 Promoter mapping indicated that AlgU is probably not directly responsible for transcription of the psl operon and the lec genes |
| GO:1900233 positive regulation of single-species biofilm formation on inanimate substrate | IMP PMID:20348252 The sigma factor AlgU plays a key role in formation of robus... | KEEP AS NON CORE | Summary: algU mutant of PAO1 is defective in attachment and robust biofilm formation, largely through indirect control of psl via ppyR. Reason: Supported by mutant and complementation data but indirect and downstream; non-core. Supporting Evidence: PMID:20348252 Promoter mapping indicated that AlgU is probably not directly responsible for transcription of the psl operon and the lec genes |
| GO:1902201 negative regulation of bacterial-type flagellum-dependent cell motility | IMP PMID:16291668 The alternative sigma factor AlgT represses Pseudomonas aeru... | KEEP AS NON CORE | Summary: AlgT represses flagellar genes by inhibiting fleQ expression (microarray, promoter fusions, FleQ rescue). Reason: Real, indirect regulatory output of AlgU in mucoid strains; non-core. Supporting Evidence: PMID:16291668 AlgT mediates the negative control of flagellum expression by inhibiting the expression of the flagellar regulator fleQ |
| GO:1902884 positive regulation of response to oxidative stress | IMP PMID:7961422 Analysis of promoters controlled by the putative sigma facto... | KEEP AS NON CORE | Summary: algU mutants are more sensitive to paraquat (superoxide) killing. Reason: Mutant sensitivity phenotype consistent with AlgU's sigma-E-like stress regulon; non-core. Supporting Evidence: PMID:7961422 The algU mutants, irrespective of the mucoid status of the parental strains, displayed increased sensitivity to killing by paraquat |
| GO:2000142 regulation of DNA-templated transcription initiation | IEA GO_REF:0000108 | ACCEPT | Summary: Inferred from sigma factor activity by inter-ontology link; the regulatory process a sigma factor performs. Reason: Correct granularity for the process side of sigma factor activity; replacement target for the GO:0006355 rows. Supporting Evidence: PMID:19730690 Sigma factors are essential subunits of prokaryotic RNA polymerase, they are involved in promoter recognition and transcription initiation file:PSEAE/algU/algU-uniprot.txt PF04542; Sigma70_r2 |
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Experiment: ChIP-seq of AlgU after D-cycloserine-induced cell wall stress to define direct targets.
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