FoxR (PA2467) is a FecR-family transmembrane anti-sigma factor of the ferrioxamine cell-surface signalling system of Pseudomonas aeruginosa. It has a cytoplasmic N-terminal region (FecR_N), a single transmembrane helix and a periplasmic FecR domain, and is encoded in the foxI-foxR (PA2468-PA2467) operon next to the ferrioxamine receptor gene foxA (PA2466). In the absence of ferrioxamine FoxR inhibits the ECF sigma factor FoxI; a foxR mutant produces FoxA independent of ferrioxamine B. FoxR self-cleaves in the periplasmic domain between Gly191 and Thr192 by an N-O acyl rearrangement; ferrioxamine binding to FoxA then triggers further proteolysis that releases FoxI activity, and the cytoplasmic N-terminal fragment has pro-sigma activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016989 sigma factor antagonist activity | IMP PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | ACCEPT | Summary: PseudoCAP IMP and a seed of the PTN001250434 IBD. In the full text (PMC page) a foxR transposon mutant expresses its receptor constitutively, independent of the siderophore, which shows that foxR inhibits FoxI. A derepression phenotype is the expected genetic readout of an anti-sigma factor; the antagonism is confirmed by later work summarised in PMID:35138377. Reason: Core function; the seed is sound. foxR has the FecR_N/FecR domain architecture of cell-surface-signalling anti-sigma factors. Supporting Evidence: PMID:35138377 The regulatory proteins FoxR and FiuR act as anti-sigma factors in that they inhibit the sigma factors FoxI and FiuI PMID:16484199 The involvement of this putative regulatory locus in the specific induction of the ferrioxamine B and ferrichrome receptors has been demonstrated |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000108 | MODIFY | Summary: Logical inference from the sigma factor antagonist activity. Sequestering an ECF sigma factor prevents it from directing RNA polymerase to its promoters, so the process is negative regulation of transcription initiation. Reason: Correct but general. GO:2000143 negative regulation of DNA-templated transcription initiation (is_a GO:0045892) is the precise process for an anti-sigma factor, and matches the GO:2000142 accepted on the cognate sigma factor reviews. Proposed replacements: negative regulation of DNA-templated transcription initiation Supporting Evidence: PMID:35138377 The regulatory proteins FoxR and FiuR act as anti-sigma factors in that they inhibit the sigma factors FoxI and FiuI PMID:16484199 The involvement of this putative regulatory locus in the specific induction of the ferrioxamine B and ferrichrome receptors has been demonstrated |
| GO:0034756 regulation of iron ion transport | IMP PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | MODIFY | Summary: Loss of foxR makes foxA expression constitutive, so the anti-sigma factor limits production of the receptor through which iron-siderophore complexes are imported. The direction of the effect is negative. Reason: Correct but general; the mutant phenotype shows negative regulation. GO:0034757 negative regulation of iron ion transport (is_a GO:0034756) is supported, mirroring the positive-regulation term used for the cognate sigma factor. Non-core. Proposed replacements: negative regulation of iron ion transport Supporting Evidence: PMID:35138377 The regulatory proteins FoxR and FiuR act as anti-sigma factors in that they inhibit the sigma factors FoxI and FiuI PMID:39138320 Iron complexed by desferioxamine G is transported by FpvB and FoxA |
| GO:0005886 plasma membrane | IC PMID:25809487 Self-cleavage of the Pseudomonas aeruginosa Cell-surface Sig... | NEW | Summary: Proposed location. The protein has a single Phobius transmembrane helix between the cytoplasmic FecR_N region and the periplasmic FecR domain, and the literature describes it as a transmembrane (cytoplasmic membrane) anti-sigma factor that relays a periplasmic signal to a cytoplasmic sigma factor. Reason: Two independent lines agree (predicted TM helix with the FecR domain architecture, and the published description); no cellular component is annotated at present. Supporting Evidence: PMID:25809487 In the absence of ferrioxamine, the activity of Ο(FoxI) is inhibited by the transmembrane anti-sigma factor FoxR. |
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