fpr encodes a monomeric FAD-containing ferredoxin--NADP+ reductase (FPR) of the plastid-type FNR family, with an N-terminal FAD-binding domain and a C-terminal NADP-binding domain. Its expression rises under iron starvation. FPR oxidises NADPH and passes the electrons to one-electron acceptors, including the [2Fe-2S] bacterioferritin-associated ferredoxin Bfd, through which it supports reduction and release of Fe(3+) from the bacterioferritin BfrB core. FPR also reduces the iron-regulated heme oxygenase directly, without a ferredoxin intermediate, and so supplies the electrons for heme degradation that frees iron from heme taken up under iron limitation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004324 ferredoxin-NADP+ reductase activity | EXP PMID:17915950 Biochemical and structural characterization of Pseudomonas a... | ACCEPT | Summary: UniProt experimental annotation; the purified enzyme is an NADPH-dependent, FAD-containing ferredoxin reductase. Reason: Direct biochemical characterisation of the purified protein with its ferredoxin Bfd, and crystal structures with FAD and NADP+ (PMID:18605699). Core MF. Supporting Evidence: PMID:17915950 the fpr gene encodes a 258-residue NADPH-dependent ferredoxin reductase (pa-FPR) that utilizes FAD as a cofactor |
| GO:0004324 ferredoxin-NADP+ reductase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from the bacterial FNR InterPro family and EC 1.18.1.2. Reason: Consistent with the experimental annotation. Supporting Evidence: PMID:17915950 the fpr gene encodes a 258-residue NADPH-dependent ferredoxin reductase (pa-FPR) that utilizes FAD as a cofactor |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO generic oxidoreductase from FAD/NAD-binding signatures. Reason: Correct but general; the specific, experimentally supported activity is GO:0004324, which the gene already carries. Proposed replacements: ferredoxin-NADP+ reductase activity Supporting Evidence: PMID:17915950 the fpr gene encodes a 258-residue NADPH-dependent ferredoxin reductase (pa-FPR) that utilizes FAD as a cofactor |
| GO:0042167 heme catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN002500048, whose sole seed is this gene's PseudoCAP IDA (PMID:17915950). Correct for fpr; heme degradation is a partner-specific role, not a property of the FNR clade. Reason: For FPR the term is supported by in vitro reconstitution with the cognate heme oxygenase, in which FPR alone delivers the electrons the oxygenase consumes. The node, however, extends heme catabolism to FNRs of organisms without a canonical heme oxygenase (E. coli, Salmonella) and to a eukaryotic genome entry. Recorded as a GO_CENTRAL defect. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002500048 · PTN002500048 SUPPORTS SOURCE BUT NOT TARGET QuickGO (2026-10-28) lists 13 GO:0042167 IBA leaves, including E. coli Fpr (P28861), Salmonella Fpr (Q8ZKP5), Yersinia, Shewanella, Xanthomonas, Neisseria (Q7DDI7, Q9JYS7) and Bradyrhizobium FNRs, P. aeruginosa PA4615 (Q9HVH6) and Nematostella A7TBA2. UniProtKB:Q9HYK7 · fpr SUPPORTS TRANSFER The target's own experimental annotation is the IBD seed; expected, not circular. Supporting Evidence: PMID:17915950 In vitro reconstitution of pa-HO catalytic activity with the newly characterized proteins led to the surprising observation that pa-FPR efficiently supports the catalytic cycle of pa-HO, without the need of a ferredoxin. |
| GO:0042167 heme catabolic process | IDA PMID:17915950 Biochemical and structural characterization of Pseudomonas a... | ACCEPT | Summary: PseudoCAP IDA; FPR supports pa-HO turnover in vitro without ferredoxin. Sole seed of the GO:0042167 IBD at PTN002500048. Reason: FPR is not a substrate of heme catabolism and its role is not mere necessity. It catalyses the NADPH-to-heme-oxygenase electron transfer that each oxygenation step consumes; GO's heme oxygenase activity definition writes the reduced reductase in as a co-substrate. This is the cofactor-supplying case of participation. The evidence is in vitro reconstitution; in vivo dependence of heme-iron use on FPR has not been tested. Comparator caveat - mammalian POR, the HO-1 electron donor, carries no heme catabolism annotation, whereas the analogous adrenodoxin reductase FDXR is annotated to steroid biosynthesis, so GO practice here is inconsistent rather than prohibitive. Supporting Evidence: PMID:17915950 In vitro reconstitution of pa-HO catalytic activity with the newly characterized proteins led to the surprising observation that pa-FPR efficiently supports the catalytic cycle of pa-HO, without the need of a ferredoxin. PMID:17915950 Given that pa-HO functions to release iron from exogenous heme acquired under iron-starvation conditions, the use of a flavoenzyme rather than an iron-sulfur center-containing protein to support heme degradation is an efficient use of resources in the cell. |
| GO:0003958 NADPH-hemoprotein reductase activity | IDA PMID:17915950 Biochemical and structural characterization of Pseudomonas a... | NEW | Summary: Proposed MF for FPR's direct reduction of heme oxygenase. Reason: FPR reduces the heme-bound P. aeruginosa heme oxygenase directly, with NADPH as donor and without a ferredoxin, which is the reaction of GO:0003958. GOA has only the ferredoxin reductase MF, which does not describe this partner. Supporting Evidence: PMID:17915950 In vitro reconstitution of pa-HO catalytic activity with the newly characterized proteins led to the surprising observation that pa-FPR efficiently supports the catalytic cycle of pa-HO, without the need of a ferredoxin. |
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Download this section (compressed HTML)Q: Should electron-donor reductases (FPR for bacterial HO, POR for mammalian HO-1) be annotated to heme catabolic process, given that GO's heme oxygenase activity definition includes the reduced reductase as a co-substrate? Current practice differs between POR (not annotated) and FDXR (annotated to steroid biosynthesis).
Experiment: Test whether an fpr deletion (or fpr/PA4615 double mutant) impairs growth on heme as sole iron source and biliverdin production in P. aeruginosa, to establish the in vivo role of FPR in heme degradation.
Type: genetic knockout with heme-iron utilisation assays
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