arh1 encodes the fission yeast mitochondrial adrenodoxin reductase-like flavoprotein, an FAD-containing NAD(P)H:ferredoxin reductase of the ferredoxin-NADP reductase type 1 family, associated with the matrix side of the inner membrane by homology. It transfers electrons from NADPH to the adrenodoxin-like ferredoxin domain of Etp1 (Etp1fd). By homology with S. cerevisiae Arh1, this electron transfer chain supports mitochondrial iron-sulfur cluster assembly, heme A synthesis and the Coq6 hydroxylation in coenzyme Q synthesis. Recombinant Arh1 binds FAD weakly, accepts electrons from both NADH and NADPH, and with Etp1fd can drive human mitochondrial cytochrome P450 reactions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004324 ferredoxin-NADP+ reductase activity | IDA PMID:18399988 The endogenous adrenodoxin reductase-like flavoprotein arh1 ... | ACCEPT | Summary: Arh1 transfers electrons from NADPH to adrenodoxin-type ferredoxin (Etp1), supporting heterologous mitochondrial P450s. Reason: Recombinant S. pombe Arh1 (A18G holoprotein) accepts electrons from NAD(P)H and reduces its ferredoxin partner Etp1fd and mammalian adrenodoxin, supporting reconstituted P450 reactions (PMID:18399988). Direct biochemical evidence for the ferredoxin reductase activity; core function, as in the S. cerevisiae ARH1 review and the module annoton. Supporting Evidence: PMID:18399988 In this paper, we present evidence that the S. pombe ferredoxin reductase, arh1, and ferredoxin, etp1fd provide mammalian class I cytochromes P450 with reduction equivalents. PMID:18399988 Arh1_A18G can substitute for AdR by interacting not only with its natural redox partner etp1fd but also with the mammalian homolog adrenodoxin. |
| GO:0004324 ferredoxin-NADP+ reductase activity | IDA PMID:21536008 Structural and thermodynamic characterization of the adrenod... | ACCEPT | Summary: Electron exchange between Arh1 and the Etp1 ferredoxin domain analysed in vitro (structural and thermodynamic study of Etp1fd). Reason: PMID:21536008 analyses electron transfer from Arh1 to Etp1(fd) and to adrenodoxin; the cached record is abstract-only and the curator read the full text. Consistent with PMID:18399988; accepted. Supporting Evidence: PMID:21536008 Analysis of the electron exchange with the S. pombe redox partner Arh1 revealed differences between Etp1(fd) and adrenodoxin, which might be linked to their different physiological functions in the mitochondria of mammals and yeast. |
| GO:0004324 ferredoxin-NADP+ reductase activity | NAS GO_REF:0000051 | ACCEPT | Summary: Author statement; consistent. Reason: PomBase NAS (GO_REF:0000051). PMID:18399988 (S. pombe) shows recombinant arh1, with its ferredoxin etp1fd, supplies reducing equivalents to class I P450s and accepts electrons from NAD(P)H; UniProt's catalytic activity (NADPH -> adrenodoxin, EC 1.18.1.6) is assigned by similarity to S. cerevisiae Arh1 (P48360). Supporting Evidence: PMID:18399988 In this paper, we present evidence that the S. pombe ferredoxin reductase, arh1, and ferredoxin, etp1fd provide mammalian class I cytochromes P450 with reduction equivalents. file:SCHPO/arh1/arh1-uniprot.txt Reaction=2 reduced [adrenodoxin] + NADP(+) + H(+) = 2 oxidized [adrenodoxin] + NADPH |
| GO:0005739 mitochondrion | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome YFP screen: mitochondrion. Reason: Genome-wide YFP-tagging screen (HDA) placed arh1 in mitochondria; consistent with its predicted transit peptide and with the mitochondrial ferredoxin partner Etp1fd. Direct evidence that cannot resolve the sub-compartment: ACCEPT at the root organelle term. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein file:SCHPO/arh1/arh1-uniprot.txt TRANSIT 1..38 |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of mitochondrial location. Reason: IBA from PAINT node PTN000234268 (PTHR48467, GO_REF:0000033). A predicted N-terminal mitochondrial transit peptide (1..38) and UniProt's curated location (mitochondrial inner membrane, by similarity to S. cerevisiae Arh1 (UniProtKB:P48360)) support the mitochondrial placement of the PAINT node; an S. pombe ORFeome screen (PMID:16823372, separate HDA row) independently finds it in mitochondria. Root organelle term kept (organelle policy). Supporting Evidence: file:SCHPO/arh1/arh1-uniprot.txt TRANSIT 1..38 file:SCHPO/arh1/arh1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt mapping; consistent. Reason: UniProt SubCell mapping (GO_REF:0000044). UniProt's curated location, mitochondrial inner membrane as a peripheral membrane protein, is by similarity to S. cerevisiae Arh1 (UniProtKB:P48360); a predicted mitochondrial transit peptide is present. The S. cerevisiae ARH1 review accepts EXP/IDA inner-membrane rows for the ortholog. Supporting Evidence: file:SCHPO/arh1/arh1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane file:SCHPO/arh1/arh1-uniprot.txt TRANSIT 1..38 |
| GO:0005743 mitochondrial inner membrane | ISO GO_REF:0000024 | ACCEPT | Summary: Transfer from S. cerevisiae Arh1 (matrix-facing inner membrane). Reason: PomBase ISO (GO_REF:0000024). UniProt's curated location, mitochondrial inner membrane as a peripheral membrane protein, is by similarity to S. cerevisiae Arh1 (UniProtKB:P48360), the ortholog this ISO row transfers from; a predicted mitochondrial transit peptide is present. The S. cerevisiae ARH1 review accepts EXP/IDA inner-membrane rows. Supporting Evidence: file:SCHPO/arh1/arh1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane file:SCHPO/arh1/arh1-uniprot.txt TRANSIT 1..38 |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Similarity; consistent. Reason: PomBase ISS (GO_REF:0000024) from P48360. UniProt's curated location, mitochondrial inner membrane as a peripheral membrane protein, is by similarity to S. cerevisiae Arh1 (UniProtKB:P48360), the ISS source; a predicted mitochondrial transit peptide is present. Supporting Evidence: file:SCHPO/arh1/arh1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane file:SCHPO/arh1/arh1-uniprot.txt TRANSIT 1..38 |
| GO:0006744 ubiquinone biosynthetic process | ISO GO_REF:0000024 | ACCEPT | Summary: Transfer from S. cerevisiae ARH1: the Arh1-Yah1 ferredoxin system supplies electrons to the Coq6 hydroxylase. Reason: PomBase ISO (GO_REF:0000024). UniProt's curated FUNCTION (by similarity to S. cerevisiae Arh1 (UniProtKB:P48360)) states the reductase is essential for coenzyme Q biosynthesis, probably by supplying electrons to the Coq6 hydroxylase; this is ortholog evidence, not tested in S. pombe. (The GOA row lists a Drosophila ortholog as its source.) In S. cerevisiae the Arh1-Yah1 chain is required for Coq6 C5 hydroxylation (accepted IMP in the ARH1 review); the reductase supplies the reducing equivalents the hydroxylation step depends on, so it does part of the work (cofactor-supply role). Not tested in S. pombe; accepted on ortholog grounds, matching the module's ferredoxin-system part. Supporting Evidence: file:SCHPO/arh1/arh1-uniprot.txt Essential for coenzyme Q biosynthesis. May be involved in the electron transfer required for the hydroxylation reaction performed by coq6. file:SCHPO/arh1/arh1-uniprot.txt Essential for coenzyme Q biosynthesis. May be involved in the electron transfer required for the hydroxylation reaction performed by coq6. |
| GO:0008860 ferredoxin-NAD+ reductase activity | IDA PMID:18399988 The endogenous adrenodoxin reductase-like flavoprotein arh1 ... | KEEP AS NON CORE | Summary: Ferredoxin reduction with NADH measured in vitro; NADPH is the physiological donor. Reason: S. pombe experiment. Recombinant Arh1 (the FAD-stabilised A18G variant) accepted electrons from NADH as well as NADPH in vitro, so NADH-dependent ferredoxin reduction is real; UniProt curates NADPH as the donor (by similarity to S. cerevisiae Arh1, P48360), so the NADH activity is kept as non-core. Supporting Evidence: PMID:18399988 The modified reductase arh1_A18G displayed spectroscopic characteristics similar to AdR and was shown to be capable of accepting electrons with no evident preference for NADH or NADPH, respectively. |
| GO:0016491 oxidoreductase activity | IBA GO_REF:0000033 | TOO GENERAL | Summary: Generic oxidoreductase; the specific ferredoxin-NADP+ reductase activity is accepted in this review. Reason: IBA from PAINT node PTN000234102 (PTHR48467, GO_REF:0000033). True but uninformative. Ferredoxin-NADP+ reductase activity (GO:0004324), accepted from S. pombe experiments (PMID:18399988) and by similarity to S. cerevisiae Arh1 (P48360), entails this term. Supporting Evidence: PMID:18399988 In this paper, we present evidence that the S. pombe ferredoxin reductase, arh1, and ferredoxin, etp1fd provide mammalian class I cytochromes P450 with reduction equivalents. file:SCHPO/arh1/arh1-uniprot.txt Reaction=2 reduced [adrenodoxin] + NADP(+) + H(+) = 2 oxidized [adrenodoxin] + NADPH |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: Generic oxidoreductase; the specific ferredoxin-NADP+ reductase activity is accepted in this review. Reason: InterPro2GO mapping (GO_REF:0000002). True but uninformative. The adrenodoxin-type ferredoxin reductase family signature (IPR021163) and S. pombe experiments (PMID:18399988) support the accepted ferredoxin-NADP+ reductase activity (GO:0004324), which entails this term. Supporting Evidence: PMID:18399988 In this paper, we present evidence that the S. pombe ferredoxin reductase, arh1, and ferredoxin, etp1fd provide mammalian class I cytochromes P450 with reduction equivalents. file:SCHPO/arh1/arh1-uniprot.txt InterPro; IPR021163; Ferredox_Rdtase_adrenod. |
| GO:0044571 [2Fe-2S] cluster assembly | IC GO_REF:0000111 | ACCEPT | Summary: Curator inference: the ferredoxin reductase-ferredoxin chain supplies electrons for mitochondrial Fe-S cluster assembly. Reason: Curator inference (IC, GO_REF:0000111). UniProt's curated FUNCTION (by similarity to S. cerevisiae Arh1 (UniProtKB:P48360)) says the reductase is required for de novo Fe-S cluster synthesis on isu1 and delivers electrons for Fe-S cluster synthesis; the IC follows from the ferredoxin reductase activity shown for S. pombe arh1 (PMID:18399988). It is an electron supplier to the assembly machinery, not a scaffold. It supplies the electrons the assembly step depends on (cofactor-supply participation). Supporting Evidence: file:SCHPO/arh1/arh1-uniprot.txt Required for the de novo synthesis of Fe-S clusters on iron sulfur cluster assembly protein isu1 file:SCHPO/arh1/arh1-uniprot.txt Involved in electron delivery for Fe-S cluster synthesis |
| GO:0071949 FAD binding | IDA PMID:18399988 The endogenous adrenodoxin reductase-like flavoprotein arh1 ... | KEEP AS NON CORE | Summary: FAD cofactor; subsidiary. Reason: Recombinant S. pombe Arh1 binds FAD only weakly, and an A18G change in the FAD-binding region gives a stable holoprotein (PMID:18399988). Genuine cofactor binding, subsidiary to the reductase activity: non-core. Supporting Evidence: PMID:18399988 The recombinant reductase showed an unusual weak binding of flavin adenine dinucleotide (FAD), which was mastered by modifying the FAD-binding region by site-directed mutagenesis yielding a stable holoprotein. |
| GO:0099128 mitochondrial [2Fe-2S] assembly complex | TAS PMID:34660592 Biogenesis of Iron-Sulfur Clusters and Their Role in DNA Met... | MARK AS OVER ANNOTATED | Summary: TAS from a review of Fe-S biogenesis; the review lists ferredoxin (Yah1) among the [2Fe-2S] assembly components and the NADPH-FDXR-FDX2 chain as electron supply, not the reductase as a complex subunit. Reason: PMID:34660592 (full text cached) is a general review. It places ferredoxin in the mitochondrial ISC assembly machinery as the electron donor and mentions the NADPH-FDXR-FDX2 electron transfer chain, but does not describe the ferredoxin reductase as a subunit of the [2Fe-2S] assembly complex. Arh1 is better described as supplying electrons to that complex via Etp1fd, which the accepted GO:0044571 row captures. The membership claim over-reaches; not removed because the curator may intend a looser sense of the complex. Supporting Evidence: PMID:34660592 This process required the presence of IBA57 and the electron transfer chain NADPH-FDXR-FDX2 file:SCHPO/arh1/arh1-uniprot.txt Involved in electron delivery for Fe-S cluster synthesis. |
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