PtxR (PA2258) is a LysR-family transcriptional activator of Pseudomonas aeruginosa, found in the human-pathogenic pseudomonads, that activates expression of the exotoxin A gene toxA and of the kgu and gad 2-ketogluconate catabolic operons. It binds a short palindromic operator overlapping the -35 region of PtoxA, Pkgu and Pgad. Its activity is antagonized by the divergently encoded LacI-family repressor PtxS, which binds PtxR directly (at PtoxA) or forms a DNA loop with it (at Pkgu and Pgad); 2-ketogluconate releases PtxS and allows PtxR-dependent transcription. PtxR also modulates quorum-sensing-controlled virulence genes: ptxR mutants make more pyocyanin and rhamnolipid gene expression and less lasB (elastase) expression.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from LysR node PTN001248394 (seeds PtxR and E. coli YjiE). Reason: Directly supported for PtxR by DNaseI footprints at PtoxA, Pkgu and Pgad. Supporting Evidence: PMID:22844393 PtxR binds to the toxA promoter, and that the operator site corresponds to a short palindrome PMID:22844393 identified a PtxR binding site in the P(kgu) and P(gad) promoters that overlaps the -35 region |
| GO:0000976 transcription cis-regulatory region binding | IPI PMID:22844393 Genes for carbon metabolism and the ToxA virulence factor in... | ACCEPT | Summary: CollecTF row: PtxR footprints at -35 of PtoxA, Pkgu and Pgad. Reason: Direct binding evidence. Supporting Evidence: PMID:22844393 PtxR binds to the -35 region of the P(toxA) promoter in front of the exotoxin A gene PMID:22844393 identified a PtxR binding site in the P(kgu) and P(gad) promoters that overlaps the -35 region |
| GO:0001216 DNA-binding transcription activator activity | IPI PMID:22844393 Genes for carbon metabolism and the ToxA virulence factor in... | ACCEPT | Summary: CollecTF row: PtxR binds and activates PtoxA and Pkgu. Reason: Binding plus loss of activation in the deletion; core function. Supporting Evidence: PMID:22844393 PtxR binds to the toxA promoter, and that the operator site corresponds to a short palindrome PMID:22844393 In this study we confirmed that in a ΞptxR background, expression of toxA is almost three-fold lower than in the parental strain, an observation which confirms the positive role of PtxR. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro LysR mapping. Reason: Entailed by GO:0001216 DNA-binding transcription activator activity, accepted here (is_a GO:0003700). |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IMP PMID:8843437 Isolation and characterization of a Pseudomonas aeruginosa g... | REMOVE | Summary: PseudoCAP IMP row. ptxR mutants have less exotoxin A activity in culture supernatants; exotoxin A (ToxA) is the ADP-ribosyltransferase, and PtxR, a LysR regulator, raises toxA transcription. Reason: Wrong gene product for the activity: the catalytic activity belongs to the target toxin, not the regulator. The term is also a poly-ADP-ribosyltransferase, whereas exotoxin A is a mono-ADP-ribosyltransferase of EF-2. The regulatory role is already captured by GO:0045893 and GO:0001216. Supporting Evidence: PMID:8843437 The deduced amino acid sequence of PtxR is homologous to that of several members of the LysR family of transcriptional activators. PMID:8843437 both mutants showed a significant reduction in the level of exotoxin A activity PMID:8843437 ptxR increases toxA and regA transcription |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA from LysR node PTN001248394, which this gene's PseudoCAP GO:0045893 IDA row seeds together with six other LysR regulators (E. coli MetR, YjiE, AaeR, YhaJ, P. aeruginosa CysB and Q9I1R1). Seed SOUND. Reason: True but entailed by GO:0045893 positive regulation of DNA-templated transcription, accepted here. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro LysR mapping. Reason: Entailed by GO:0045893, accepted here. |
| GO:0032993 protein-DNA complex | IPI PMID:22844393 Genes for carbon metabolism and the ToxA virulence factor in... | KEEP AS NON CORE | Summary: CollecTF protein-DNA complex row. Reason: CollecTF convention for a TF-operator complex; true but not informative as a location. Supporting Evidence: PMID:22844393 PtxR binds to the toxA promoter, and that the operator site corresponds to a short palindrome |
| GO:0045862 positive regulation of proteolysis | IMP PMID:16803594 PtxR modulates the expression of QS-controlled virulence fac... | MARK AS OVER ANNOTATED | Summary: PseudoCAP IMP row. ptxR mutants have lower lasB (elastase) expression, which the authors place downstream of lasI. Proteolysis here is by the secreted elastase. Reason: PtxR acts on transcription; any effect on proteolysis is through LasB expression and probably indirect through quorum sensing. Abstract only, so not removed; the term over-reaches the evidence. Not a PAINT seed. Supporting Evidence: PMID:16803594 ptxR mutation increased the expression of the rhamnolipid synthesis gene rhlA but decreased lasB expression PMID:16803594 it positively regulates the expression of lasB through lasI |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:22844393 Genes for carbon metabolism and the ToxA virulence factor in... | ACCEPT | Summary: PseudoCAP IDA seed of the PTN001248394 GO:0006355 IBD. PtxR footprints a palindrome at -35 of PtoxA (also Pkgu, Pgad), and toxA expression drops three-fold in the deletion. Reason: Seed SOUND (full text read): binding plus activation in vivo. Supporting Evidence: PMID:22844393 PtxR binds to the toxA promoter, and that the operator site corresponds to a short palindrome PMID:22844393 In this study we confirmed that in a ΞptxR background, expression of toxA is almost three-fold lower than in the parental strain, an observation which confirms the positive role of PtxR. |
| GO:1900377 negative regulation of secondary metabolite biosynthetic process | IMP PMID:16803594 PtxR modulates the expression of QS-controlled virulence fac... | MODIFY | Summary: PseudoCAP IMP row: ptxR mutants overproduce pyocyanin and express phzA1-G1 more. Reason: The secondary metabolite is pyocyanin, a phenazine; GO:1900981 negative regulation of phenazine biosynthetic process is the precise term. Probably indirect (via rhlI/pqsABCDE per the abstract), so non-core. Proposed replacements: negative regulation of phenazine biosynthetic process Supporting Evidence: PMID:16803594 Mutation of ptxR in PAO1 increased pyocyanin production. PMID:16803594 PtxR reduced the expression of the pyocyanin operon phzA1-G1 but not phzA2-G2 |
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Experiment: Screen ligands of the purified PtxR effector-binding domain (thermal shift) and test candidates for effects on PtoxA footprinting.
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