fur (PA4764) encodes the ferric uptake regulator of Pseudomonas aeruginosa, an essential homodimeric Fur-family metalloregulator with a structural zinc site and a regulatory iron site. Loaded with Fe(II) under iron-replete conditions, Fur binds Fur-box operators overlapping the promoters of at least 24 genes and represses them. Its targets include pvdS and pchR, the activators of pyoverdine and pyochelin siderophore synthesis, the haem-uptake loci phu and has, siderophore receptor and sigma-factor genes, the fagA-fumC-orfX-sodA operon, and the PrrF1/PrrF2 small RNAs, whose iron-limitation induction indirectly down-regulates iron-using and iron-storage genes. Through this network Fur couples iron status to iron acquisition, oxidative-stress defence, central metabolism and exotoxin A expression.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN002112386 (Fur superfamily), seeded by many experimentally characterised Fur-family regulators including this gene. Reason: Fur binds Fur-box operator sequences in promoters of iron-regulated genes, shown by footprinting for many P. aeruginosa targets. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002112386 · PTN002112386 SUPPORTS TRANSFER Operator binding is shared by all Fur-family metalloregulators. UniProtKB:Q03456 · fur SUPPORTS TRANSFER The target is one of 15 seeds; expected, not circular. Supporting Evidence: PMID:10658665 Binding of Fur was demonstrated by DNase footprinting of two adjacent 'Fur boxes' that overlapped both the phuR and phuSTUVW promoters. PMID:8633080 DNA fragments obtained after at least three exponential enrichment cycles were cloned and subjected to DNA mobility-shift assays and DNase I footprint analyses to verify the specific interaction with the Fur protein in vitro. |
| GO:0000976 transcription cis-regulatory region binding | IEP PMID:21546589 FvbA is required for vibriobactin utilization in Pseudomonas... | ACCEPT | Summary: CollecTF IEP; the abstract reports only preliminary involvement of Fur in fvbA regulation. Reason: Fur operator binding is well established for P. aeruginosa Fur; this row adds a target promoter. The cited abstract gives little binding detail, but the term is correct for the gene. Supporting Evidence: PMID:21546589 preliminary analyses revealed the involvement of vibriobactin, Fur protein and an IclR-type regulator, FvbR (PA4157), in fvbA regulation PMID:8633080 DNA fragments obtained after at least three exponential enrichment cycles were cloned and subjected to DNA mobility-shift assays and DNase I footprint analyses to verify the specific interaction with the Fur protein in vitro. |
| GO:0000976 transcription cis-regulatory region binding | IPI PMID:10658665 Genetics and regulation of two distinct haem-uptake systems,... | ACCEPT | Summary: CollecTF IPI from Fur footprinting / mobility-shift assays on a P. aeruginosa promoter. Reason: Fur operator binding is well established for P. aeruginosa Fur; this row adds a target promoter. Direct DNA-binding evidence. Supporting Evidence: PMID:10658665 Binding of Fur was demonstrated by DNase footprinting of two adjacent 'Fur boxes' that overlapped both the phuR and phuSTUVW promoters. |
| GO:0000976 transcription cis-regulatory region binding | IPI PMID:8633080 Gene repression by the ferric uptake regulator in Pseudomona... | ACCEPT | Summary: CollecTF IPI from Fur footprinting / mobility-shift assays on a P. aeruginosa promoter. Reason: Fur operator binding is well established for P. aeruginosa Fur; this row adds a target promoter. Direct DNA-binding evidence. Supporting Evidence: PMID:8633080 DNA fragments obtained after at least three exponential enrichment cycles were cloned and subjected to DNA mobility-shift assays and DNase I footprint analyses to verify the specific interaction with the Fur protein in vitro. |
| GO:0000976 transcription cis-regulatory region binding | IPI PMID:9045799 An operon containing fumC and sodA encoding fumarase C and m... | ACCEPT | Summary: CollecTF IPI from Fur footprinting / mobility-shift assays on a P. aeruginosa promoter. Reason: Fur operator binding is well established for P. aeruginosa Fur; this row adds a target promoter. Direct DNA-binding evidence. Supporting Evidence: PMID:9045799 DNA footprinting analysis revealed a 37-bp region that included the Fur binding sites and was protected by Fur. |
| GO:0001217 DNA-binding transcription repressor activity | IEP PMID:21546589 FvbA is required for vibriobactin utilization in Pseudomonas... | ACCEPT | Summary: CollecTF annotation of DNA-binding repressor activity on a Fur target promoter. Reason: Fur-Fe(II) binds Fur boxes overlapping target promoters and represses them under iron-replete conditions; this is the core activity. The cited abstract is thin, but the activity is correct for the gene. Supporting Evidence: PMID:21546589 preliminary analyses revealed the involvement of vibriobactin, Fur protein and an IclR-type regulator, FvbR (PA4157), in fvbA regulation PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:0001217 DNA-binding transcription repressor activity | IPI PMID:10658665 Genetics and regulation of two distinct haem-uptake systems,... | ACCEPT | Summary: CollecTF annotation of DNA-binding repressor activity on a Fur target promoter. Reason: Fur-Fe(II) binds Fur boxes overlapping target promoters and represses them under iron-replete conditions; this is the core activity. Supporting Evidence: PMID:10658665 Binding of Fur was demonstrated by DNase footprinting of two adjacent 'Fur boxes' that overlapped both the phuR and phuSTUVW promoters. PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:0001217 DNA-binding transcription repressor activity | IPI PMID:8633080 Gene repression by the ferric uptake regulator in Pseudomona... | ACCEPT | Summary: CollecTF annotation of DNA-binding repressor activity on a Fur target promoter. Reason: Fur-Fe(II) binds Fur boxes overlapping target promoters and represses them under iron-replete conditions; this is the core activity. Supporting Evidence: PMID:8633080 DNA fragments obtained after at least three exponential enrichment cycles were cloned and subjected to DNA mobility-shift assays and DNase I footprint analyses to verify the specific interaction with the Fur protein in vitro. PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:0001217 DNA-binding transcription repressor activity | IPI PMID:9045799 An operon containing fumC and sodA encoding fumarase C and m... | ACCEPT | Summary: CollecTF annotation of DNA-binding repressor activity on a Fur target promoter. Reason: Fur-Fe(II) binds Fur boxes overlapping target promoters and represses them under iron-replete conditions; this is the core activity. Supporting Evidence: PMID:9045799 DNA footprinting analysis revealed a 37-bp region that included the Fur binding sites and was protected by Fur. PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:0003700 DNA-binding transcription factor activity | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA from PTN002112386. Correct but general. Reason: P. aeruginosa Fur acts as an iron-dependent repressor; the child GO:0001217 DNA-binding transcription repressor activity, which the gene already carries by CollecTF IPI, is the precise term. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002112386 · PTN002112386 SUPPORTS TRANSFER Unsigned TF activity is right for the superfamily (some members activate). UniProtKB:Q03456 · fur SUPPORTS TRANSFER The target is one of the seeds; expected, not circular. Proposed replacements: DNA-binding transcription repressor activity Supporting Evidence: PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from the Fur family signature (IPR002481). Correct but general. Reason: P. aeruginosa Fur acts as an iron-dependent repressor; the child GO:0001217 DNA-binding transcription repressor activity, which the gene already carries by CollecTF IPI, is the precise term. Proposed replacements: DNA-binding transcription repressor activity Supporting Evidence: PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: UniProt SubCell mapping (by similarity). Reason: Correct but general; the gene carries the more specific GO:0005829 cytosol by IBA, appropriate for a soluble repressor. Proposed replacements: cytosol Supporting Evidence: PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN002112441 (E. coli Fur seed). Reason: Fur is a soluble cytoplasmic DNA-binding repressor; cytosol is consistent with its action on chromosomal promoters. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002112441 · PTN002112441 SUPPORTS TRANSFER UniProtKB:P0A9A9 · E. coli Fur SUPPORTS TRANSFER Supporting Evidence: PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | MODIFY | Summary: Combined IEA (ARBA and InterPro). Correct but general. Reason: Fur represses its targets; the signed child GO:0045892, supported experimentally, is the precise term. Proposed replacements: negative regulation of DNA-templated transcription Supporting Evidence: PMID:8633080 The expression of at least 24 distinct genes of Pseudomonas aeruginosa PAO1 is under direct control of the "ferric uptake regulator" (Fur). |
| GO:0008198 ferrous iron binding | TAS PMID:8522528 Role of the ferric uptake regulator of Pseudomonas aeruginos... | ACCEPT | Summary: PseudoCAP TAS; Fur uses Fe(II) as co-repressor. Reason: Purified Fur recognises target promoters as Fur-Fe(II); a distinct iron site was characterised spectroscopically alongside the structural zinc site. Ferrous iron sensing is how Fur reads iron status. Supporting Evidence: PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment PMID:12581348 were performed in order to characterize the distinct zinc and iron binding sites in solution |
| GO:0008270 zinc ion binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA from PTN002112386 (E. coli and M. tuberculosis seeds). Reason: The P. aeruginosa Fur crystal structure contains bound Zn2+, with distinct zinc and iron sites; zinc is structural rather than the iron-sensing activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002112386 · PTN002112386 SUPPORTS TRANSFER UniProtKB:P0A9A9 · E. coli Fur SUPPORTS TRANSFER Supporting Evidence: PMID:12581348 Here, we present the first crystal structure of Fur from P. aeruginosa in complex with Zn2+ determined at a resolution of 1.8 A. |
| GO:0019290 siderophore biosynthetic process | IMP PMID:8478325 Coordinate regulation of siderophore and exotoxin A producti... | MODIFY | Summary: CACAO IMP; Fur mutants constitutively produce siderophores. Reason: Fur does not carry out any step of siderophore biosynthesis; the mutants overproduce siderophores because Fur represses the pathway (via pvdS and pchR). The claim is regulatory, so it is corrected laterally to GO:1900705, which the gene already carries. Proposed replacements: negative regulation of siderophore biosynthetic process Supporting Evidence: PMID:8478325 These manganese-resistant Fur mutants constitutively produce siderophores and exotoxin A when grown in concentrations of iron that normally repress their production. PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:0032993 protein-DNA complex | IEP PMID:21546589 FvbA is required for vibriobactin utilization in Pseudomonas... | KEEP AS NON CORE | Summary: CollecTF annotation of Fur-operator complex from binding assays on a target promoter. Reason: True for a DNA-binding repressor bound at its operator, but a transient complex adding little beyond the operator-binding MF. Supporting Evidence: PMID:21546589 preliminary analyses revealed the involvement of vibriobactin, Fur protein and an IclR-type regulator, FvbR (PA4157), in fvbA regulation |
| GO:0032993 protein-DNA complex | IPI PMID:10658665 Genetics and regulation of two distinct haem-uptake systems,... | KEEP AS NON CORE | Summary: CollecTF annotation of Fur-operator complex from binding assays on a target promoter. Reason: True for a DNA-binding repressor bound at its operator, but a transient complex adding little beyond the operator-binding MF. Supporting Evidence: PMID:10658665 Binding of Fur was demonstrated by DNase footprinting of two adjacent 'Fur boxes' that overlapped both the phuR and phuSTUVW promoters. |
| GO:0032993 protein-DNA complex | IPI PMID:8633080 Gene repression by the ferric uptake regulator in Pseudomona... | KEEP AS NON CORE | Summary: CollecTF annotation of Fur-operator complex from binding assays on a target promoter. Reason: True for a DNA-binding repressor bound at its operator, but a transient complex adding little beyond the operator-binding MF. Supporting Evidence: PMID:8633080 DNA fragments obtained after at least three exponential enrichment cycles were cloned and subjected to DNA mobility-shift assays and DNase I footprint analyses to verify the specific interaction with the Fur protein in vitro. |
| GO:0032993 protein-DNA complex | IPI PMID:9045799 An operon containing fumC and sodA encoding fumarase C and m... | KEEP AS NON CORE | Summary: CollecTF annotation of Fur-operator complex from binding assays on a target promoter. Reason: True for a DNA-binding repressor bound at its operator, but a transient complex adding little beyond the operator-binding MF. Supporting Evidence: PMID:9045799 DNA footprinting analysis revealed a 37-bp region that included the Fur binding sites and was protected by Fur. |
| GO:0045892 negative regulation of DNA-templated transcription | EXP PMID:10658665 Genetics and regulation of two distinct haem-uptake systems,... | ACCEPT | Summary: CollecTF EXP for Fur repression of a target promoter. Reason: Fur directly represses iron-regulated promoters it binds; consistent with the core role. Supporting Evidence: PMID:10658665 Binding of Fur was demonstrated by DNase footprinting of two adjacent 'Fur boxes' that overlapped both the phuR and phuSTUVW promoters. PMID:8633080 The expression of at least 24 distinct genes of Pseudomonas aeruginosa PAO1 is under direct control of the "ferric uptake regulator" (Fur). |
| GO:0045892 negative regulation of DNA-templated transcription | EXP PMID:21546589 FvbA is required for vibriobactin utilization in Pseudomonas... | ACCEPT | Summary: CollecTF EXP for Fur repression of a target promoter. Reason: Fur directly represses iron-regulated promoters it binds; consistent with the core role. Supporting Evidence: PMID:21546589 preliminary analyses revealed the involvement of vibriobactin, Fur protein and an IclR-type regulator, FvbR (PA4157), in fvbA regulation PMID:8633080 The expression of at least 24 distinct genes of Pseudomonas aeruginosa PAO1 is under direct control of the "ferric uptake regulator" (Fur). |
| GO:0045892 negative regulation of DNA-templated transcription | EXP PMID:8633080 Gene repression by the ferric uptake regulator in Pseudomona... | ACCEPT | Summary: CollecTF EXP for Fur repression of a target promoter. Reason: Fur directly represses iron-regulated promoters it binds; consistent with the core role. Supporting Evidence: PMID:8633080 The expression of at least 24 distinct genes of Pseudomonas aeruginosa PAO1 is under direct control of the "ferric uptake regulator" (Fur). PMID:8633080 The expression of at least 24 distinct genes of Pseudomonas aeruginosa PAO1 is under direct control of the "ferric uptake regulator" (Fur). |
| GO:0045892 negative regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN002112386, seeded by many Fur-family repressors including this gene. Reason: Fur represses at least 24 P. aeruginosa genes directly; repression is conserved across the Fur superfamily. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002112386 · PTN002112386 SUPPORTS TRANSFER UniProtKB:Q03456 · fur SUPPORTS TRANSFER The target is one of 17 seeds; expected, not circular. Supporting Evidence: PMID:8633080 The expression of at least 24 distinct genes of Pseudomonas aeruginosa PAO1 is under direct control of the "ferric uptake regulator" (Fur). |
| GO:0045892 negative regulation of DNA-templated transcription | IEP PMID:15210934 Identification of tandem duplicate regulatory small RNAs in ... | ACCEPT | Summary: CollecTF IEP for Fur repression of a target promoter. Reason: Fur directly represses iron-regulated promoters it binds; consistent with the core role. Supporting Evidence: PMID:15210934 a functional Fur box precedes each PMID:8633080 The expression of at least 24 distinct genes of Pseudomonas aeruginosa PAO1 is under direct control of the "ferric uptake regulator" (Fur). |
| GO:0045892 negative regulation of DNA-templated transcription | IEP PMID:9045799 An operon containing fumC and sodA encoding fumarase C and m... | ACCEPT | Summary: CollecTF IEP for Fur repression of a target promoter. Reason: Fur directly represses iron-regulated promoters it binds; consistent with the core role. Supporting Evidence: PMID:9045799 DNA footprinting analysis revealed a 37-bp region that included the Fur binding sites and was protected by Fur. PMID:8633080 The expression of at least 24 distinct genes of Pseudomonas aeruginosa PAO1 is under direct control of the "ferric uptake regulator" (Fur). |
| GO:1900705 negative regulation of siderophore biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN002112483, whose sole seed is this gene's PseudoCAP IMP (PMID:8885270). The target in its own WITH/FROM is expected. Reason: Correct for P. aeruginosa Fur, which represses the pyoverdine and pyochelin regulators pvdS and pchR. The node placement is questionable for leaves from bacteria that make no siderophores (recorded as a GO_CENTRAL defect), but that does not affect this gene. Propagation Review Root cause: NO FAILURE CORE Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN002112483 · PTN002112483 SUPPORTS SOURCE BUT NOT TARGET 12 Fur leaves (12 taxa); includes Neisseria, Helicobacter and Coxiella Fur, from bacteria not known to make siderophores. UniProtKB:Q03456 · fur SUPPORTS TRANSFER The target's own IMP is the sole seed; sound for P. aeruginosa. Supporting Evidence: PMID:8885270 The A2 and A4 mutants expressed higher levels of siderophores in iron-deficient media and in iron-replete media. PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:1900705 negative regulation of siderophore biosynthetic process | IMP PMID:8885270 Ferric uptake regulator mutants of Pseudomonas aeruginosa wi... | ACCEPT | Summary: PseudoCAP IMP; sole seed of the GO:1900705 IBD at PTN002112483 and co-seed (with Zur/np20) of the GO:1900376 IBD at PTN002112386. Reason: Fur point mutants (H86R, H86Y) overproduce siderophores even in iron-replete media, and the mutant Fur proteins bind the pvdS promoter with reduced affinity; purified Fur-Fe(II) recognises the pvdS and pchR promoters. Fur therefore does the regulatory work itself, as the repressor of the pathway activators. This is a direct regulatory role, not a downstream phenotype. Abstract only in the cache. Supporting Evidence: PMID:8885270 The A2 and A4 mutants expressed higher levels of siderophores in iron-deficient media and in iron-replete media. PMID:8885270 Fur from the A2 and A4 mutants and from the C6Rv revertant was able to bind to the target DNA, but with reduced affinity by comparison to wild-type Fur. PMID:8522528 are specifically recognized by Fur-Fe(II) are presented, suggesting that PA-Fur represses expression of pchR and pvdS during growth in an iron-replete environment |
| GO:1901668 regulation of superoxide dismutase activity | IMP PMID:8763923 Ferric uptake regulator (Fur) mutants of Pseudomonas aerugin... | MARK AS OVER ANNOTATED | Summary: PseudoCAP IMP; fur mutants have increased Mn-SOD activity. Not a PAINT seed. Reason: The change in SOD activity reflects Fur repression of sodA transcription (Fur binds the iron boxes of the sodA operon); Fur does not regulate the enzyme's activity. The transcriptional role is already captured by GO:0045892. Supporting Evidence: PMID:8763923 Purified wild-type Fur bound more avidly than mutant Fur to a PCR product containing two palindromic 19-bp "iron box" regions controlling expression of an operon containing the sodA gene that encodes Mn-SOD. PMID:9045799 DNA footprinting analysis revealed a 37-bp region that included the Fur binding sites and was protected by Fur. |
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Download this section (compressed HTML)Q: Which P. aeruginosa Fur targets (beyond pvdS and pchR) are bound directly in vivo, and are any directly activated by Fur rather than indirectly via the PrrF sRNAs?
Experiment: ChIP-seq of Fur under iron-replete and iron-limited conditions in PAO1 and a prrF1-prrF2 deletion, to separate direct repression, direct activation and sRNA-mediated effects.
Type: ChIP-seq
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