coq6 encodes the fission yeast Coq6 flavin-dependent monooxygenase of the UbiH/COQ6 family, a peripheral protein on the matrix side of the mitochondrial inner membrane and part of the CoQ biosynthetic complex. Coq6 hydroxylates C5 of the ring of 4-hydroxy-3-decaprenylbenzoate, the first ring modification after prenylation, probably using electrons supplied from NADPH through the mitochondrial ferredoxin reductase and ferredoxin. Its orthologs have also been proposed to hydroxylate C1 after Coq4-dependent decarboxylation, but this step is now attributed mainly to Coq4. Deletion of coq6 abolishes CoQ10 synthesis; human COQ6, and Arabidopsis COQ6 given a mitochondrial targeting sequence, complement the deletion.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| 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 Coq6 in mitochondria, in agreement with the single-gene Coq6-GFP/MitoTracker result (PMID:24911838). Direct evidence from an assay 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 PMID:24911838 These results are consistent with those of a previous study [44] that examined the localization of 4,431 S. pombe proteins |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of mitochondrial location. Reason: IBA from PAINT node PTN000350182 (PTHR43876, GO_REF:0000033). Mitochondrial location of S. pombe Coq6 is shown directly: Coq6-GFP expressed in the deletion strain localised to mitochondria (Hayashi et al. 2014); the curated UniProt location (inner membrane, PubMed:24911838 and PubMed:16823372) entails the mitochondrion. The PAINT node agrees with the experimental data on the gene itself. Supporting Evidence: PMID:24911838 The Dps1, Ppt1/Coq2, Coq3, Coq4, Coq5, Coq6, Coq7, Coq8, and Coq9 GFP fusion proteins also localized to the mitochondria file:SCHPO/coq6/coq6-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005739 mitochondrion | IDA PMID:24911838 Functional conservation of coenzyme Q biosynthetic genes amo... | ACCEPT | Summary: Mitochondrial localisation of the tagged protein. Reason: Coq6-GFP expressed in the corresponding deletion strain localises to MitoTracker-stained mitochondria (PMID:24911838). Whole-organelle co-staining: ACCEPT at the root organelle term. Supporting Evidence: PMID:24911838 The Dps1, Ppt1/Coq2, Coq3, Coq4, Coq5, Coq6, Coq7, Coq8, and Coq9 GFP fusion proteins also localized to the mitochondria PMID:24911838 The results presented here demonstrate that all of the S. pombe Coq proteins localize to mitochondria, indicating that CoQ biosynthesis occurs in these cellular compartments. |
| GO:0005743 mitochondrial inner membrane | EXP PMID:24911838 Functional conservation of coenzyme Q biosynthetic genes amo... | ACCEPT | Summary: PomBase EXP for inner-membrane location from the systematic S. pombe coq study. Reason: PMID:24911838 (full text cached) localises Coq6-GFP to mitochondria by co-staining, without sub-mitochondrial fractionation; UniProt tags its inner-membrane line with this paper, PMID:16823372 and HAMAP MF_03193. The claim agrees with the S. cerevisiae ortholog, whose EXP/IDA inner-membrane rows are accepted in the COQ6 review; accepted, not second-guessed. Supporting Evidence: PMID:24911838 The Dps1, Ppt1/Coq2, Coq3, Coq4, Coq5, Coq6, Coq7, Coq8, and Coq9 GFP fusion proteins also localized to the mitochondria file:SCHPO/coq6/coq6-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt mapping; consistent. Reason: This IEA is the UniProt SubCell mapping of the curated location line, which cites PubMed:16823372, PubMed:24911838 and HAMAP rule MF_03193. Those assays resolve the mitochondrion; the inner-membrane (matrix-side peripheral) placement rests on the HAMAP rule, i.e. on the Coq6 orthologs of the CoQ synthome. Consistent with the EXP row. Supporting Evidence: file:SCHPO/coq6/coq6-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0006744 ubiquinone biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; ubiquinone biosynthesis step. Reason: IBA from PAINT node PTN000350182 (PTHR43876, GO_REF:0000033). Supported by experimental data on the gene itself: the S. pombe coq6 deletion cannot make CoQ10 and human COQ6 restores it (Hayashi et al. 2014); the UniProt PATHWAY line carries ECO:0000269 to that paper. Coq6 catalyses the C5 hydroxylation, so it does part of the work. Supporting Evidence: PMID:24911838 the ฮcoq4, ฮcoq5, ฮcoq6, and ฮcoq9 strains are also unable to synthesize CoQ PMID:24911838 Similar results were obtained when HsCOQ4 and HsCOQ6 were expressed in the ฮcoq4 and ฮcoq6 strains, respectively (Figures 6A and 6B). file:SCHPO/coq6/coq6-uniprot.txt Cofactor biosynthesis; ubiquinone biosynthesis. |
| GO:0006744 ubiquinone biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Mapping; consistent. Reason: UniRule/InterPro/ARBA mapping (GO_REF:0000120). Same claim as the IBA and IMP rows; the UniProt PATHWAY line carries ECO:0000269 to Hayashi et al. 2014, where the coq6 deletion cannot make CoQ10. Supporting Evidence: PMID:24911838 the ฮcoq4, ฮcoq5, ฮcoq6, and ฮcoq9 strains are also unable to synthesize CoQ file:SCHPO/coq6/coq6-uniprot.txt Cofactor biosynthesis; ubiquinone biosynthesis. |
| GO:0006744 ubiquinone biosynthetic process | IMP PMID:24911838 Functional conservation of coenzyme Q biosynthetic genes amo... | ACCEPT | Summary: Deletion abolishes CoQ10 production (systematic analysis of the S. pombe coq genes). Reason: Deletion of the gene abolishes CoQ10 synthesis and gives the shared coq-mutant phenotypes (PMID:24911838). Coq6 performs a step of the pathway, so it does part of the work; core process. Supporting Evidence: PMID:24911838 Here, we expand these findings by identifying ten genes (dps1, dlp1, ppt1, and coq3-9) that are required for CoQ synthesis. PMID:24911838 Overall, these data indicate that, like the S. pombe ฮdps1, ฮdlp1, ฮppt1/coq2, ฮcoq3, ฮcoq7, and ฮcoq8 strains described previously, the ฮcoq4, ฮcoq5, ฮcoq6, and ฮcoq9 strains are also unable to synthesize CoQ. |
| GO:0016491 oxidoreductase activity | IBA GO_REF:0000033 | TOO GENERAL | Summary: Generic oxidoreductase; true but uninformative, entailed by the specific Coq6 hydroxylase activities. Reason: IBA from PAINT node PTN000350182 (PTHR43876, GO_REF:0000033). The parent term is correct: by UbiH/COQ6 family membership (HAMAP MF_03193) Coq6 is the FAD-dependent C5-ring hydroxylase of ubiquinone biosynthesis, and the S. pombe deletion is CoQ-deficient (Hayashi et al. 2014). GO:0106364 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity, asserted elsewhere in this review, is_a monooxygenase/oxidoreductase activity and entails this term. The PAINT node placement is not in question; the row is simply less informative than the specific activity. Supporting Evidence: file:SCHPO/coq6/coq6-uniprot.txt Required for the C5-ring hydroxylation during ubiquinone biosynthesis by catalyzing the hydroxylation of 4-hydroxy-3-(all-trans-decaprenyl)benzoic acid to 3,4-dihydroxy-5-(all-trans-decaprenyl)benzoic acid. file:SCHPO/coq6/coq6-uniprot.txt Belongs to the UbiH/COQ6 family. |
| GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen | IEA GO_REF:0000002 | TOO GENERAL | Summary: Monooxygenase (paired donors, O2) parent term; true but entailed by the specific Coq6 hydroxylase activity. Reason: InterPro2GO mapping (GO_REF:0000002). By UbiH/COQ6 family membership (HAMAP MF_03193, InterPro IPR010971) Coq6 hydroxylates its polyprenylbenzoate substrate with O2, using electrons from reduced ferredoxin, i.e. a paired-donor monooxygenase. GO:0106364, asserted elsewhere in this review, is_a GO:0016713 which is_a this term, so the row is correct but uninformative. Supporting Evidence: file:SCHPO/coq6/coq6-uniprot.txt Reaction=4-hydroxy-3-(all-trans-decaprenyl)benzoate + 2 reduced [2Fe-2S]-[ferredoxin] + O2 + 2 H(+) = 3,4-dihydroxy-5-(all-trans-decaprenyl)benzoate + 2 oxidized [2Fe-2S]-[ferredoxin] + H2O file:SCHPO/coq6/coq6-uniprot.txt Belongs to the UbiH/COQ6 family. |
| GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen | IEA GO_REF:0000104 | MODIFY | Summary: Flavin/flavoprotein-donor monooxygenase class term from UniRule; the monooxygenase essence is right but the curated Coq6 reactions use reduced ferredoxin as the external donor. Reason: UniRule mapping (GO_REF:0000104, HAMAP MF_03193). Coq6 is an FAD-containing monooxygenase, so the monooxygenase essence is sound, but GO:0016712 names reduced flavin or flavoprotein as the external donor, whereas the curated Coq6 reactions use reduced [2Fe-2S] ferredoxin (GO:0016713 branch, parent of GO:0106364). The bound FAD is captured by the FAD binding row. MODIFY to the specific C5-hydroxylase term the gene already carries, as in the S. cerevisiae COQ6 review. No S. pombe enzymology exists. Proposed replacements: 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity Supporting Evidence: file:SCHPO/coq6/coq6-uniprot.txt Reaction=4-hydroxy-3-(all-trans-decaprenyl)benzoate + 2 reduced [2Fe-2S]-[ferredoxin] + O2 + 2 H(+) = 3,4-dihydroxy-5-(all-trans-decaprenyl)benzoate + 2 oxidized [2Fe-2S]-[ferredoxin] + H2O file:SCHPO/coq6/coq6-uniprot.txt FAD-dependent monooxygenase required for two non-consecutive steps during ubiquinone biosynthesis. |
| GO:0031314 extrinsic component of mitochondrial inner membrane | IC GO_REF:0000111 | ACCEPT | Summary: Peripheral component on the matrix side of the inner membrane, where the CoQ synthome assembles. Reason: Curator inference (IC, GO_REF:0000111). UniProt places Coq6 on the matrix side of the inner membrane as a peripheral membrane protein; the topology rests on HAMAP MF_03193 (orthologous CoQ synthome), while the mitochondrial location is experimental (PubMed:16823372, PubMed:24911838). The record has no TRANSMEM feature, consistent with a peripheral protein. The S. cerevisiae COQ6 review accepts the same term. Supporting Evidence: file:SCHPO/coq6/coq6-uniprot.txt Mitochondrion inner membrane; Peripheral membrane protein; Matrix side |
| GO:0031314 extrinsic component of mitochondrial inner membrane | IEA GO_REF:0000104 | ACCEPT | Summary: Peripheral component on the matrix side of the inner membrane, where the CoQ synthome assembles. Reason: UniRule mapping (GO_REF:0000104). Same claim as the IC row: peripheral, matrix-side inner-membrane placement from HAMAP MF_03193; no TRANSMEM feature in the record. The topology rests on the orthologous CoQ synthome, not on an S. pombe sub-mitochondrial assay. The S. cerevisiae COQ6 review accepts the same term. Supporting Evidence: file:SCHPO/coq6/coq6-uniprot.txt Mitochondrion inner membrane; Peripheral membrane protein; Matrix side |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: FAD binding (parent term); true but entailed by the GO:0071949 FAD binding row. Reason: InterPro2GO mapping (GO_REF:0000002). GO:0071949 FAD binding is_a this term and is asserted in this review (row on IPR002938), so this row is correct but general. FAD binding rests on family/domain evidence (FAD cofactor in HAMAP MF_03193; Pfam FAD_binding_3), not on an S. pombe experiment. Supporting Evidence: file:SCHPO/coq6/coq6-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692 file:SCHPO/coq6/coq6-uniprot.txt Pfam; PF01494; FAD_binding_3; 1. |
| GO:0071949 FAD binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: FAD cofactor binding; true but subsidiary to the hydroxylase activities. Reason: InterPro2GO mapping (GO_REF:0000002). Family/domain evidence: Coq6 carries the FAD-binding domain (InterPro IPR002938, Pfam FAD_binding_3) and HAMAP MF_03193 assigns FAD as cofactor. Cofactor binding is part of how the hydroxylase works, not a separate core function. Same action as the S. cerevisiae and human COQ6 reviews. Supporting Evidence: file:SCHPO/coq6/coq6-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692 file:SCHPO/coq6/coq6-uniprot.txt InterPro; IPR002938; FAD-bd. file:SCHPO/coq6/coq6-uniprot.txt Pfam; PF01494; FAD_binding_3; 1. |
| GO:0106364 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC/RHEA mapping: C5 ring hydroxylase. Reason: EC/Rhea/InterPro mapping (GO_REF:0000120). No S. pombe enzymology exists. The curated HAMAP rule MF_03193 (UbiH/COQ6 family) assigns the C5-ring hydroxylation (EC 1.14.15.45); complementation of the coq6 deletion by human COQ6 and by mitochondrially targeted Arabidopsis COQ6 (Hayashi et al. 2014) shows the S. pombe protein fills the COQ6 step in vivo. Core function, matching the S. cerevisiae and human COQ6 reviews and the module annoton. Supporting Evidence: file:SCHPO/coq6/coq6-uniprot.txt Required for the C5-ring hydroxylation during ubiquinone biosynthesis by catalyzing the hydroxylation of 4-hydroxy-3-(all-trans-decaprenyl)benzoic acid to 3,4-dihydroxy-5-(all-trans-decaprenyl)benzoic acid. file:SCHPO/coq6/coq6-uniprot.txt Belongs to the UbiH/COQ6 family. PMID:24911838 Similar results were obtained when HsCOQ4 and HsCOQ6 were expressed in the ฮcoq4 and ฮcoq6 strains, respectively (Figures 6A and 6B). |
| GO:0120538 2-methoxy-6-polyprenolphenol 4-hydroxylase activity | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: C1 hydroxylation of 2-methoxy-6-decaprenylphenol, assigned to Coq6 by the HAMAP rule; the C1 step is now attributed to COQ4 in vivo, and Coq6 C1-hydroxylase activity is shown only in vitro for the human enzyme. Reason: Rhea/EC mapping (GO_REF:0000120, EC 1.14.15.46) from HAMAP MF_03193 by similarity only; there is no S. pombe evidence. The orthologs disagree: human COQ6 hydroxylates a short-chain analog at C1 in vitro with FDXR/FDX2 (PMID:38425362), whereas PMID:38295803 shows that the eukaryotic C1 decarboxylation and hydroxylation occur in one COQ4-catalysed oxidative decarboxylation, so the 2-methoxy-6-polyprenylphenol substrate may not form in vivo. Real in vitro activity of uncertain physiological relevance: MARK_AS_OVER_ANNOTATED, not core. This sits between the S. cerevisiae COQ6 review (REMOVE) and the human COQ6 review (ACCEPT, backed by IDA). The module likewise assigns the C1 reactions to Coq4, while the PomBase GO-CAM gives the C1 hydroxylation to coq6. Supporting Evidence: file:SCHPO/coq6/coq6-uniprot.txt Also acts downstream of COQ4, for the C1-hydroxylation during ubiquinone biosynthesis by catalyzing the hydroxylation of 2-methoxy-6-(all-trans-decaprenyl)phenol to 2-methoxy-6-(all-trans-decaprenyl)benzene-1,4-diol. PMID:38295803 Here, we provide evidence that these two reactions occur in a single oxidative decarboxylation step catalyzed by COQ4. PMID:38425362 Indeed, COQ6, in the presence of FDXR and FDX2, produced the 4b adduct corroborating its dual functionality as both a C5 and C1 hydroxylase |
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Download this section (compressed HTML)Q: Does S. pombe Coq6 hydroxylate C1 of 2-methoxy-6-decaprenylphenol in vivo, or does Coq4 perform both C1 reactions as in PMID:38295803? The PomBase GO-CAM (662af8fa00000408) and HAMAP MF_03193 currently assign GO:0120538 to coq6.
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