FoxA (PA2466) is the TonB-dependent outer-membrane receptor and transporter for ferrioxamine-type hydroxamate siderophores in Pseudomonas aeruginosa: ferrioxamine B (desferrioxamine B), ferrioxamine G, nocardamine (ferrioxamine E) and bisucaberin. It has the beta-barrel and plug domains of the TonB-dependent receptor family and an N-terminal STN signalling domain, which makes it a TonB-dependent transducer. Ferrioxamine binding to FoxA is signalled across the envelope to the anti-sigma factor FoxR, whose processing releases the ECF sigma factor FoxI to induce foxA transcription; FoxA is produced only under iron limitation in the presence of its siderophore. FpvB provides an overlapping uptake route for some ferrioxamines.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007166 cell surface receptor signaling pathway | IMP PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | ACCEPT | Summary: FoxA is the receptor of the Fox cell-surface signalling system: ferrioxamine binding to FoxA leads to FoxR processing and FoxI release. Reason: The signalling role of FoxA is established in later work and fits its STN domain. The cached paper is abstract-only, so the FoxA mutant data behind the row could not be read; the curator's call is consistent with the established pathway and is accepted. Supporting Evidence: PMID:35138377 The binding of Fe3+ferrioxamine B to the FoxA OM protein triggers the transcription of ferrioxamine transport genes PMID:25809487 Upon binding of ferrioxamine by the FoxA receptor, FoxR is processed by a complex proteolytic cascade leading to the release and activation of Ο(FoxI) file:PSEAE/foxA/foxA-uniprot.txt SM00965; STN; 1. |
| GO:0009279 cell outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Outer-membrane location of a TonB-dependent siderophore receptor; IBD seeded by E. coli FhuA and FhuE and P. aeruginosa FpvA and FptA. Reason: FoxA has a signal peptide, the plug and the TonB-dependent receptor beta-barrel, and FoxA was found in outer-membrane protein profiles. The IBA is sound. Supporting Evidence: file:PSEAE/foxA/foxA-uniprot.txt PF00593; TonB_dep_Rec_b-barrel; 1. PMID:16484199 we have used a proteomic approach to identify the inducing conditions for P. aeruginosa TonB-dependent receptors |
| GO:0009279 cell outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Cell outer membrane location from the family signature. Reason: Consistent with the domain architecture and the IBA row. Supporting Evidence: file:PSEAE/foxA/foxA-uniprot.txt PF00593; TonB_dep_Rec_b-barrel; 1. |
| GO:0015343 siderophore-iron transmembrane transporter activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: True but entailed by the siderophore uptake transporter term. Reason: GO:0015344 siderophore uptake transmembrane transporter activity, accepted here, is_a GO:0015343 siderophore-iron transmembrane transporter activity. Supporting Evidence: PMID:39138320 FoxA of the ferric forms of nocardamine, bisucaberin, DFOB and DFOG file:PSEAE/foxA/foxA-uniprot.txt IPR010105; TonB_sidphr_rcpt. |
| GO:0015344 siderophore uptake transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: FoxA imports ferric ferrioxamines across the outer membrane; IBD sound. Reason: Core molecular function, shown with foxA mutants in growth and 55Fe uptake assays (PMID:39138320). No more specific GO term exists for ferrioxamine uptake. The IBD at PTN000793005 also rests on E. coli FhuA and Fiu experimental rows; FoxA appears in its own WITH/FROM because it is one of the seeds. Supporting Evidence: PMID:39138320 FoxA of the ferric forms of nocardamine, bisucaberin, DFOB and DFOG PMID:39138320 Iron complexed by desferioxamine G is transported by FpvB and FoxA PMID:39138320 FoxA recognizes those of the DFOB family |
| GO:0015344 siderophore uptake transmembrane transporter activity | IMP PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | ACCEPT | Summary: PseudoCAP seed row for the PTN000793005 IBD. The term is correct for FoxA; whether this paper itself contains the transport phenotype could not be checked. Reason: FoxA is the ferrioxamine uptake receptor (mutant growth and 55Fe uptake, PMID:39138320). The abstract of this paper reports proteomic identification of FoxA as the ferrioxamine B-induced receptor and its regulation, and is silent on mutant transport assays; the full text could not be retrieved. The curator read the full text, the function is correct, and the IBD stands on other seeds regardless, so the row is accepted and its seed verdict recorded as UNVERIFIABLE. Supporting Evidence: PMID:16484199 Two of them are only produced in the presence of the hydroxamate siderophores ferrioxamine B and ferrichrome PMID:39138320 FoxA of the ferric forms of nocardamine, bisucaberin, DFOB and DFOG PMID:39138320 Iron complexed by desferioxamine G is transported by FpvB and FoxA |
| GO:0015891 siderophore transport | IEA GO_REF:0000120 | MODIFY | Summary: Correct but general; FoxA imports ferric siderophores into the cell. Reason: The gene carries GO:0033214 siderophore-iron import into cell (IBA), which is the specific process and which the mutant uptake data support. GO:0033214 is not a descendant of GO:0015891 in the current ontology, so MODIFY rather than TOO_GENERAL. Proposed replacements: siderophore-iron import into cell Supporting Evidence: PMID:39138320 Iron complexed by desferioxamine G is transported by FpvB and FoxA |
| GO:0015891 siderophore transport | IMP PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | MODIFY | Summary: Correct but general; refine to siderophore-iron import into cell. Reason: Same refinement as the IEA row. The paper's own data could not be checked (abstract-only cache); the process is correct for FoxA. Proposed replacements: siderophore-iron import into cell Supporting Evidence: PMID:16484199 Two of them are only produced in the presence of the hydroxamate siderophores ferrioxamine B and ferrichrome PMID:39138320 Iron complexed by desferioxamine G is transported by FpvB and FoxA |
| GO:0019867 outer membrane | IDA PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | MODIFY | Summary: FoxA was identified in outer-membrane protein profiles; the specific location is the cell outer membrane. Reason: GO:0019867 outer membrane is the generic term; GO:0009279 cell outer membrane, already on the gene (IBA, IEA), is the specific location for a Gram-negative receptor. Proposed replacements: cell outer membrane Supporting Evidence: PMID:16484199 we have used a proteomic approach to identify the inducing conditions for P. aeruginosa TonB-dependent receptors file:PSEAE/foxA/foxA-uniprot.txt PF00593; TonB_dep_Rec_b-barrel; 1. |
| GO:0019867 outer membrane | IEA GO_REF:0000002 | MODIFY | Summary: Generic outer membrane from the STN domain mapping; refine to cell outer membrane. Reason: Correct but general; the gene carries GO:0009279 cell outer membrane. Proposed replacements: cell outer membrane Supporting Evidence: file:PSEAE/foxA/foxA-uniprot.txt PF00593; TonB_dep_Rec_b-barrel; 1. |
| GO:0033214 siderophore-iron import into cell | IBA GO_REF:0000033 | ACCEPT | Summary: FoxA imports ferric ferrioxamines into the cell; IBD sound. Reason: No more specific GO process exists for ferrioxamine import, so this is as precise as warranted. The IBD at PTN000793005 is seeded by FiuA, E. coli FhuE and E. coli Fiu (IDA, IMP). Supporting Evidence: PMID:39138320 Iron complexed by desferioxamine G is transported by FpvB and FoxA PMID:39138320 FoxA of the ferric forms of nocardamine, bisucaberin, DFOB and DFOG |
| GO:0038023 signaling receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: FoxA is a TonB-dependent transducer; signaling receptor activity applies. Reason: FoxA has the N-terminal STN signalling domain and its ferrioxamine binding triggers FoxR processing and FoxI release. Supporting Evidence: file:PSEAE/foxA/foxA-uniprot.txt SM00965; STN; 1. PMID:35138377 The binding of Fe3+ferrioxamine B to the FoxA OM protein triggers the transcription of ferrioxamine transport genes |
| GO:0038023 signaling receptor activity | IMP PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | ACCEPT | Summary: Signalling receptor of the Fox cell-surface signalling system. Reason: Consistent with the STN domain and the Fox pathway; the paper's own data could not be checked (abstract-only cache), so the curator's call is accepted. Supporting Evidence: PMID:16484199 The involvement of this putative regulatory locus in the specific induction of the ferrioxamine B and ferrichrome receptors has been demonstrated PMID:35138377 The binding of Fe3+ferrioxamine B to the FoxA OM protein triggers the transcription of ferrioxamine transport genes |
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Download this section (compressed HTML)Q: Should GO have a specific ferrioxamine import term, given that FoxA, E. coli FhuE and Yersinia FoxA-type receptors are all annotated only to the generic siderophore-iron import term?
Experiment: Measure FoxI-dependent foxA promoter induction by ferrioxamine B in FoxA variants lacking the STN domain or carrying a TonB-box mutation, to separate signalling from transport.
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