FiuA (PA0470) is the TonB-dependent outer-membrane receptor and transporter for the fungal hydroxamate siderophore ferrichrome in Pseudomonas aeruginosa. It has the 22-strand beta-barrel and plug domains of the TonB-dependent receptor family plus an N-terminal STN signalling domain, which makes it a TonB-dependent transducer. FiuA carries about 80% of ferric-ferrichrome uptake across the outer membrane, using energy from TonB1, and also imports the ferrichrome-type siderophores ferricrocin, ferrichrysin and rhodotorulic acid; FpvB provides a secondary route. Ferrichrome binding to FiuA also signals through the anti-sigma factor FiuR to release the ECF sigma factor FiuI (PA0472), which induces fiuA transcription under iron limitation. In the periplasm the inner-membrane permease FiuB and the acetyltransferase FiuC complete iron release, and acylated desferrichrome is recycled to the medium.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007166 cell surface receptor signaling pathway | IMP PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | ACCEPT | Summary: FiuA is the outer-membrane receptor of the Fiu cell-surface signalling system: ferrichrome binding to FiuA is signalled through FiuR to the sigma factor FiuI, which induces fiuA. Reason: FiuA has the N-terminal STN signalling domain that defines TonB-dependent transducers, and it is encoded next to the fiuI-fiuR sigma/anti-sigma pair whose role in ferrichrome-specific induction of fiuA was shown in this paper. The cached file is abstract-only, so the FiuA mutant data the curator coded could not be read; the function is consistent with the domain architecture and the established Fiu pathway, so the row is accepted. Supporting Evidence: PMID:16484199 both receptor genes are located next to a regulatory locus encoding an extracytoplasmic function sigma factor and a transmembrane sensor PMID:16484199 The involvement of this putative regulatory locus in the specific induction of the ferrioxamine B and ferrichrome receptors has been demonstrated file:PSEAE/fiuA/fiuA-uniprot.txt SM00965; STN; 1. PMID:35138377 TDPs may contain an additional signaling domain and an extra N-terminal extension with unknown function |
| GO:0009279 cell outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: TonB-dependent siderophore receptors are integral beta-barrel proteins of the cell outer membrane; the IBD is seeded by E. coli FhuA and FhuE and P. aeruginosa FpvA and FptA. Reason: FiuA has a signal peptide, the plug domain and the TonB-dependent receptor beta-barrel. The node is a clade of outer-membrane TonB-dependent siderophore receptors and its seeds have experimental outer-membrane locations, so the cell outer membrane IBA is sound for FiuA. Supporting Evidence: file:PSEAE/fiuA/fiuA-uniprot.txt PF00593; TonB_dep_Rec_b-barrel; 1. file:PSEAE/fiuA/fiuA-uniprot.txt IPR010105; TonB_sidphr_rcpt. PMID:20047910 ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter |
| GO:0009279 cell outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Cell outer membrane location, from the TonB-dependent siderophore receptor family signature. Reason: Consistent with the TonB-dependent receptor beta-barrel and with the IBA row. Supporting Evidence: file:PSEAE/fiuA/fiuA-uniprot.txt PF00593; TonB_dep_Rec_b-barrel; 1. PMID:20047910 ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter |
| GO:0015343 siderophore-iron transmembrane transporter activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: Correct but general; FiuA is a ferrichrome transporter. Reason: GO:0042929 ferrichrome transmembrane transporter activity, accepted in this review from the mutant uptake data, is_a GO:0015343 siderophore-iron transmembrane transporter activity, so this row adds nothing. Supporting Evidence: PMID:20047910 ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter file:PSEAE/fiuA/fiuA-uniprot.txt IPR010105; TonB_sidphr_rcpt. |
| GO:0015344 siderophore uptake transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: FiuA takes up ferric siderophores of the ferrichrome type across the outer membrane, so the siderophore uptake transporter term holds. The IBD stands on E. coli Fiu and FhuA (IDA, IMP) and on FoxA. Reason: FiuA is a TonB-dependent siderophore uptake transporter of the outer membrane. GO:0042929 ferrichrome transmembrane transporter activity, also accepted, is not an is_a descendant of GO:0015344 (both are under GO:0015343), so this row is not redundant: it records the uptake direction. The IBD at PTN000793005 rests on E. coli Fiu and FhuA experimental annotations and on the PseudoCAP FoxA row; FiuA belongs to that clade. Supporting Evidence: PMID:20047910 ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter PMID:39138320 FiuA is the TBDT of the ferric forms of ferrichrome, ferricrocin, ferrichrysin and RHODO file:PSEAE/fiuA/fiuA-uniprot.txt IPR010105; TonB_sidphr_rcpt. |
| GO:0015891 siderophore transport | IEA GO_REF:0000120 | MODIFY | Summary: Correct but general; FiuA imports ferric ferrichrome into the cell. Reason: The gene already carries GO:0042928 ferrichrome import into cell (IMP), which the 55Fe uptake data support. GO:0042928 is not a descendant of GO:0015891 in the current ontology, so this row is a MODIFY to the specific term rather than TOO_GENERAL. Proposed replacements: ferrichrome import into cell Supporting Evidence: PMID:20047910 ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter |
| GO:0019867 outer membrane | IDA PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | MODIFY | Summary: FiuA was identified in outer-membrane protein profiles of ferrichrome-grown cells; the specific location is the cell outer membrane. Reason: GO:0019867 outer membrane is the generic term; for a Gram-negative bacterium the specific location is GO:0009279 cell outer membrane, which the gene already carries (IBA, IEA). The proteomic detection of FiuA in this paper supports the location. 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/fiuA/fiuA-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 already carries GO:0009279 cell outer membrane (IBA, IEA), which is the specific term for a Gram-negative outer-membrane receptor. Proposed replacements: cell outer membrane Supporting Evidence: file:PSEAE/fiuA/fiuA-uniprot.txt PF00593; TonB_dep_Rec_b-barrel; 1. |
| GO:0033214 siderophore-iron import into cell | IBA GO_REF:0000033 | TOO GENERAL | Summary: True, but entailed by ferrichrome import into cell, which FiuA carries from its own mutant uptake data. Reason: GO:0042928 ferrichrome import into cell, accepted in this review, is_a GO:0033214 siderophore-iron import into cell. The IBD at PTN000793005 is sound: FiuA is one of its three seeds, and E. coli Fiu (IDA, IMP) alone supports it. FiuA appearing in its own WITH/FROM reflects the experimental grounding on this gene. Supporting Evidence: PMID:20047910 ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter |
| GO:0038023 signaling receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: FiuA is a TonB-dependent transducer with an STN signalling domain; signaling receptor activity applies. Reason: The N-terminal STN domain (residues 57-108) is the periplasmic signalling domain that contacts the anti-sigma factor in TonB-dependent transducers. Together with the adjacent fiuI-fiuR regulatory locus, this supports a signalling receptor role in addition to transport. Supporting Evidence: file:PSEAE/fiuA/fiuA-uniprot.txt SM00965; STN; 1. PMID:35138377 TDPs may contain an additional signaling domain and an extra N-terminal extension with unknown function PMID:16484199 both receptor genes are located next to a regulatory locus encoding an extracytoplasmic function sigma factor and a transmembrane sensor |
| GO:0038023 signaling receptor activity | IMP PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | ACCEPT | Summary: Signalling receptor of the Fiu cell-surface signalling system. Reason: Consistent with the STN domain and the FiuI/FiuR pathway. The cached paper is abstract-only, so the mutant experiment behind the row could not be checked; the function is well grounded in the domain architecture and in the regulation shown in this paper, 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 file:PSEAE/fiuA/fiuA-uniprot.txt SM00965; STN; 1. |
| GO:0042928 ferrichrome import into cell | IMP PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | ACCEPT | Summary: FiuA imports ferric ferrichrome; this paper identified FiuA as the ferrichrome-induced receptor. Reason: The function is established by 55Fe uptake in a fiuA mutant (PMID:20047910). Whether this earlier paper itself reported a fiuA mutant growth or uptake phenotype could not be checked (abstract-only cache); the term is correct for FiuA, so the curator's row 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:20047910 ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter |
| GO:0042928 ferrichrome import into cell | IMP PMID:20047910 The ferrichrome uptake pathway in Pseudomonas aeruginosa inv... | ACCEPT | Summary: 55Fe-ferrichrome uptake depends mainly on FiuA (80%), with TonB1 energising transport. Reason: Direct mutant uptake data for FiuA and the core process of the gene. This PseudoCAP row seeds the PTN000793005 IBD of GO:0033214 and is sound. Supporting Evidence: PMID:20047910 ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter PMID:20047910 the energy required for both pathways of ferrichrome uptake is provided by the inner membrane protein TonB1 PMID:39138320 FiuA is the TBDT of the ferric forms of ferrichrome, ferricrocin, ferrichrysin and RHODO |
| GO:0042929 ferrichrome transmembrane transporter activity | IMP PMID:16484199 The heterologous siderophores ferrioxamine B and ferrichrome... | ACCEPT | Summary: FiuA is the ferrichrome outer-membrane transporter. Reason: Correct for FiuA on the strength of PMID:20047910 and PMID:39138320; this paper's own data could not be checked (abstract-only cache), so the curator's row is accepted rather than second-guessed. Supporting Evidence: PMID:20047910 ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter PMID:39138320 FiuA is the TBDT of the ferric forms of ferrichrome, ferricrocin, ferrichrysin and RHODO |
| GO:0042929 ferrichrome transmembrane transporter activity | IMP PMID:20047910 The ferrichrome uptake pathway in Pseudomonas aeruginosa inv... | ACCEPT | Summary: FiuA transports ferric ferrichrome across the outer membrane (TonB-dependent transporter). Reason: Core molecular function, from mutant 55Fe uptake. Later work extends FiuA substrates to ferricrocin, ferrichrysin and rhodotorulic acid, all ferrichrome-type siderophores. Supporting Evidence: PMID:20047910 ferrichrome is transported across the outer membrane primarily (80%) by the FiuA receptor and to a lesser extent (20%) by a secondary transporter PMID:39138320 FiuA is the TBDT of the ferric forms of ferrichrome, ferricrocin, ferrichrysin and RHODO PMID:39138320 FiuA predominantly recognizes siderophores of the ferrichrome subtype |
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Download this section (compressed HTML)Q: Does ferrichrome binding to FiuA signal through FiuR independently of transport, as shown for FpvA and FecA, and which residues of the STN domain contact FiuR?
Experiment: Compare fiuA-lacZ induction by ferrichrome in a fiuA STN-domain deletion and in a TonB-box mutant to separate the signalling and transport functions of FiuA.
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