PvdS (PA2426) is the iron-starvation extracytoplasmic function (ECF) sigma factor of Pseudomonas aeruginosa PAO1. pvdS transcription is repressed by Fur in iron-replete cells. Under iron limitation PvdS binds core RNA polymerase, about 1:1, and directs the holoenzyme to promoters carrying the iron-starvation (IS) box, which acts as its -35 element. It drives transcription of the pyoverdine biosynthesis genes (pvdA, pvdD, pvdE, pvdF and others) and of the virulence genes toxA (exotoxin A), prpL and regA/ptxR. Its activity is modulated by ferri-pyoverdine through the FpvA receptor and the inner-membrane anti-sigma factor FpvR. FpvR retains part of the PvdS pool at the membrane; pyoverdine signalling releases it to the cytosol. PvdS is therefore the key transcriptional link between iron starvation, siderophore production and virulence factor expression.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IMP PMID:11222621 Analysis of promoters recognized by PvdS, an extracytoplasmi... | MODIFY | Summary: CollecTF row. PvdS-RNAP binds pvd promoters only when the IS box, the PvdS -35 element, is present, i.e. sequence-specific recognition of core promoter elements. Reason: Correct but general: the bound element is the -35 core promoter element, so GO:0001046 core promoter sequence-specific DNA binding (is_a GO:0000976) is the precise term. The binding is by the holoenzyme, as for any sigma factor. Proposed replacements: core promoter sequence-specific DNA binding Supporting Evidence: PMID:11222621 IS box elements participate in sequence-specific recognition by PvdS to enable initiation of transcription from pvd promoters |
| GO:0001216 DNA-binding transcription activator activity | IMP PMID:11222621 Analysis of promoters recognized by PvdS, an extracytoplasmi... | MODIFY | Summary: CollecTF row coding PvdS as a DNA-binding transcription activator. Reason: PvdS is a sigma factor, not an activator that binds a cis-element to recruit polymerase. GO:0016987 (is_a GO:0003700) is the correct sibling term. Proposed replacements: sigma factor activity Supporting Evidence: PMID:11222621 Band shift assays and in vitro transcription experiments showed that a complex of PvdS and core RNA polymerase required the presence of an IS box in order to bind to and initiate transcription from pvd promoters |
| 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/pvdS/pvdS-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/pvdS/pvdS-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/pvdS/pvdS-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 pvdS 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/pvdS/pvdS-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/pvdS/pvdS-uniprot.txt PF04542; Sigma70_r2 |
| GO:0006355 regulation of DNA-templated transcription | IMP PMID:7751284 Cloning and characterization of pvdS, a gene required for py... | MODIFY | Summary: PseudoCAP IMP and seed of the GO:0006355 IBD on PTN002455017. The abstract states that pvdS is required for expression from pyoverdine promoters and drives them in E. coli; this directly supports transcriptional regulation by PvdS. Reason: Seed verdict SOUND. The term is right but general; the evidence (promoter-specific transcription, later shown to be initiation by PvdS-RNAP) supports GO:2000142, which the gene carries. Refining the gene-level row does not affect the IBD, since GO:2000142 is a descendant of the node term. Proposed replacements: regulation of DNA-templated transcription initiation Supporting Evidence: PMID:7751284 The pvdS gene is required for expression from promoters of at least two pyoverdine synthesis genes and can cause expression from these promoters in Escherichia coli, where they are otherwise inactive |
| 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). pvdS 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/pvdS/pvdS-uniprot.txt TIGR02937; sigma70-ECF file:PSEAE/pvdS/pvdS-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:10692351 Functional analysis of PvdS, an iron starvation sigma factor... | ACCEPT | Summary: PseudoCAP IDA and seed. PvdS forms 1:1 complexes with core RNAP and promotes holoenzyme binding to the pvdA promoter: direct biochemical evidence of sigma factor activity. Reason: Seed verdict SOUND: the paper supports sigma factor activity for this gene, and the term is the core molecular function. Supporting Evidence: PMID:10692351 it spontaneously forms 1:1 complexes with the core fraction of RNA polymerase |
| GO:0016987 sigma factor activity | IDA PMID:10873648 Characterization of an ECF sigma factor protein from Pseudom... | ACCEPT | Summary: PseudoCAP IDA and seed. Purified PvdS confers promoter-specific binding and in vitro transcription on core RNAP and co-purifies with P. aeruginosa RNAP: 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:10873648 These results show that PvdS is a sigma factor protein. |
| 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/pvdS/pvdS-uniprot.txt PF04542; Sigma70_r2 file:PSEAE/pvdS/pvdS-uniprot.txt TIGR02937; sigma70-ECF |
| GO:0032993 protein-DNA complex | IMP PMID:11222621 Analysis of promoters recognized by PvdS, an extracytoplasmi... | KEEP AS NON CORE | Summary: CollecTF row: PvdS-RNAP holoenzyme bound at pvd promoters forms a protein-DNA complex. Reason: True (the promoter-bound holoenzyme) but transient and a consequence of the sigma factor activity. Supporting Evidence: PMID:11222621 Band shift assays and in vitro transcription experiments showed that a complex of PvdS and core RNA polymerase required the presence of an IS box in order to bind to and initiate transcription from pvd promoters |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:11222621 Analysis of promoters recognized by PvdS, an extracytoplasmi... | MODIFY | Summary: CollecTF IDA: PvdS-RNAP initiates transcription from IS-box promoters in vitro. Reason: Correct but general; the 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:11222621 Band shift assays and in vitro transcription experiments showed that a complex of PvdS and core RNA polymerase required the presence of an IS box in order to bind to and initiate transcription from pvd promoters |
| GO:0071281 cellular response to iron ion | EXP PMID:8633080 Gene repression by the ferric uptake regulator in Pseudomona... | KEEP AS NON CORE | Summary: pvdS expression is repressed by Fur in response to iron (Fur SELEX and RNase protection). This is a response of the pvdS gene, at the level of its own expression. Reason: True in the sense GO uses for expression responses, but the response is carried out by Fur acting on the pvdS promoter, not by PvdS activity; peripheral to the gene product's function. Supporting Evidence: PMID:8633080 While four PIGs are identical to already known genes (pfeR, pvdS, tonB, and fumC, respectively) |
| GO:1900378 positive regulation of secondary metabolite biosynthetic process | IDA PMID:10692351 Functional analysis of PvdS, an iron starvation sigma factor... | MODIFY | Summary: Positive regulation of pyoverdine (siderophore) biosynthesis: PvdS is the sigma factor for the pvd biosynthetic promoters, and pvdS mutants make no pyoverdine. Reason: Correct but general. Pyoverdine is a siderophore, and the specific term GO:1900706 positive regulation of siderophore biosynthetic process (is_a GO:1900378) fits. Proposed replacements: positive regulation of siderophore biosynthetic process Supporting Evidence: PMID:10692351 thereby promoting in vitro binding of the PvdS-RNAP holoenzyme to the promoter region of the pvdA gene |
| GO:1900378 positive regulation of secondary metabolite biosynthetic process | IDA PMID:18047579 Intracellular levels and activity of PvdS, the major iron st... | MODIFY | Summary: Positive regulation of pyoverdine (siderophore) biosynthesis: PvdS is the sigma factor for the pvd biosynthetic promoters, and pvdS mutants make no pyoverdine. Reason: Correct but general. Pyoverdine is a siderophore, and the specific term GO:1900706 positive regulation of siderophore biosynthetic process (is_a GO:1900378) fits. Proposed replacements: positive regulation of siderophore biosynthetic process Supporting Evidence: PMID:18047579 Pyoverdine signalling does not affect the PvdS cellular content but facilitates PvdS release from the membrane |
| GO:1900378 positive regulation of secondary metabolite biosynthetic process | IMP PMID:15073293 Global regulation of quorum sensing and virulence by VqsR in... | MODIFY | Summary: PseudoCAP IMP from the VqsR paper. The abstract concerns a vqsR mutant with reduced siderophore-gene transcripts and does not mention pvdS. Reason: The claim (PvdS positively regulates pyoverdine biosynthesis) is true and is refined to GO:1900706 as on the other rows of this term. This reference, however, does not appear to support it for pvdS (see source defect); full text not accessible. Proposed replacements: positive regulation of siderophore biosynthetic process Supporting Evidence: PMID:15073293 the vqsR mutant harboured less mRNA transcript for the production of siderophores |
| GO:1900378 positive regulation of secondary metabolite biosynthetic process | IMP PMID:18048935 Regulation of the Pseudomonas aeruginosa toxA, regA and ptxR... | MODIFY | Summary: Positive regulation of pyoverdine (siderophore) biosynthesis: PvdS is the sigma factor for the pvd biosynthetic promoters, and pvdS mutants make no pyoverdine. Reason: Correct but general. Pyoverdine is a siderophore, and the specific term GO:1900706 positive regulation of siderophore biosynthetic process (is_a GO:1900378) fits. Proposed replacements: positive regulation of siderophore biosynthetic process Supporting Evidence: PMID:18048935 optimal toxA, regA and pvdD expression and pyoverdine production required PvdS |
| GO:1900378 positive regulation of secondary metabolite biosynthetic process | IMP PMID:7651323 A positive regulatory gene, pvdS, for expression of pyoverdi... | MODIFY | Summary: Positive regulation of pyoverdine (siderophore) biosynthesis: PvdS is the sigma factor for the pvd biosynthetic promoters, and pvdS mutants make no pyoverdine. Reason: Correct but general. Pyoverdine is a siderophore, and the specific term GO:1900706 positive regulation of siderophore biosynthetic process (is_a GO:1900378) fits. Proposed replacements: positive regulation of siderophore biosynthetic process Supporting Evidence: PMID:7651323 A genomic pvdS mutant of PAO, constructed by allelic exchange mutagenesis, produced no pyoverdin and did not allow transcription from the pvd promoters |
| GO:1900378 positive regulation of secondary metabolite biosynthetic process | IMP PMID:8636031 Iron-regulated transcription of the pvdA gene in Pseudomonas... | MODIFY | Summary: Positive regulation of pyoverdine (siderophore) biosynthesis: PvdS is the sigma factor for the pvd biosynthetic promoters, and pvdS mutants make no pyoverdine. Reason: Correct but general. Pyoverdine is a siderophore, and the specific term GO:1900706 positive regulation of siderophore biosynthetic process (is_a GO:1900378) fits. Proposed replacements: positive regulation of siderophore biosynthetic process Supporting Evidence: PMID:8636031 Transcription from the pvdA promoter did not occur in a heterologous host unless in the presence of the pvdS gene in trans and was abrogated in a pvdS mutant of P. aeruginosa |
| 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/pvdS/pvdS-uniprot.txt PF04542; Sigma70_r2 |
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Download this section (compressed HTML)Q: What prevents purified PvdS-RNAP from transcribing pvdA in vitro (PMID:10692351) while other preparations transcribe pvd promoters (PMID:10873648)? Is an additional activator needed at some IS-box promoters?
Experiment: ChIP-seq of PvdS under iron limitation to define the direct regulon and the IS-box consensus genome-wide.
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