COQ6 (YGR255C) encodes an FAD-dependent monooxygenase (UbiH/COQ6 family) of coenzyme Q6 (ubiquinone) biosynthesis in Saccharomyces cerevisiae. Coq6 catalyses the C5-hydroxylation of the aromatic ring, converting 4-hydroxy-3-hexaprenylbenzoate (HHB) to 3,4-dihydroxy-5-hexaprenylbenzoate (DHHB; EC 1.14.15.45), the substrate of the Coq3 O-methyltransferase. Electrons are supplied from NADPH via the mitochondrial ferredoxin reductase Arh1 and ferredoxin Yah1. When Q6 is made from para-aminobenzoate, Coq6 also performs the C4-deamination, hydroxylating 3-hexaprenyl-4-aminobenzoate at C5 and then replacing the C4 amino group with a hydroxyl. Coq6 is imported into mitochondria in a membrane-potential-dependent manner and is a peripheral protein on the matrix side of the inner membrane, a member of the Coq4-organised CoQ synthome. The ring C1 hydroxylation once attributed to Coq6 by analogy with bacterial UbiH is instead achieved through a COQ4-dependent oxidative decarboxylation. coq6 mutants lack Q6, accumulate HHB and cannot respire; their defect is bypassed by vanillic acid or 3,4-dihydroxybenzoate.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Sickmann et al. 2003 mitochondrial proteome detected Coq6. Correct; precise location is the matrix face of the inner membrane. Supporting Evidence: PMID:14576278 The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS. PMID:12721307 Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Reinders et al. 2006 PROMITO mitochondrial proteome detected Coq6. Correct. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified PMID:12721307 Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Renvoise et al. 2014 mitochondrial (phospho)proteome detected Coq6. Correct. Supporting Evidence: PMID:24769239 overall quantitative proteomic and phosphoproteomic study of isolated mitochondria PMID:12721307 Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from COQ6 node PTN000350182 (human COQ6, mouse Coq6, S. pombe, trypanosomatid orthologues, SGD Coq6). Eukaryotic COQ6 proteins are mitochondrial; correct for yeast Coq6. Supporting Evidence: PMID:12721307 The Coq6 polypeptide is imported into the mitochondria in a membrane potential-dependent manner. |
| GO:0005743 mitochondrial inner membrane | EXP PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Inner-membrane annotation citing the Sickmann 2003 mitochondrial proteome paper (abstract-only cache; the sub-mitochondrial detail may be in the full text). The location is independently established by Gin et al. 2003, so deferring to the curator. Supporting Evidence: PMID:14576278 The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS. PMID:12721307 Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:12721307 The Saccharomyces cerevisiae COQ6 gene encodes a mitochondri... | ACCEPT | Summary: Gin et al. 2003 showed Coq6 is a peripheral membrane protein on the matrix side of the inner mitochondrial membrane. Correct. Supporting Evidence: PMID:12721307 Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:24406904 Coenzyme Q supplementation or over-expression of the yeast C... | ACCEPT | Summary: He et al. 2014 restate the matrix-side peripheral inner-membrane location of Coq6. Correct. Supporting Evidence: PMID:24406904 yeast Coq7 is a peripheral membrane protein on the matrix side as are Coq1, Coq3, Coq4, Coq5, Coq6, Coq8, and Coq9 polypeptides |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0168) based on experimental data. Correct. Supporting Evidence: file:yeast/COQ6/COQ6-uniprot.txt -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:12721307 Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA (PWY3O-19) applying the pathway-default cytosol compartment. Wrong for Coq6, which is imported into mitochondria and acts on the matrix side of the inner membrane. Supporting Evidence: PMID:12721307 Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. PMID:12721307 The Coq6 polypeptide is imported into the mitochondria in a membrane potential-dependent manner. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA (PWY3O-862 superpathway) applying cytosol. Same error; Coq6 is mitochondrial. Supporting Evidence: PMID:12721307 Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. PMID:12721307 The Coq6 polypeptide is imported into the mitochondria in a membrane potential-dependent manner. |
| GO:0006744 ubiquinone biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from COQ6 node PTN000350182. Correct. Supporting Evidence: PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. PMID:12721307 coq6 mutants are unable to grow on nonfermentable carbon sources and do not synthesize Q but instead accumulate the Q biosynthetic intermediate 3-hexaprenyl-4-hydroxybenzoic acid. |
| GO:0006744 ubiquinone biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, InterPro IPR000689/IPR010971, UniRule, UniPathway UPA00232). Correct. Supporting Evidence: file:yeast/COQ6/COQ6-uniprot.txt -!- FUNCTION: FAD-dependent monooxygenase required for two non-consecutive |
| GO:0006744 ubiquinone biosynthetic process | IMP PMID:21944752 Coenzyme Q biosynthesis: Coq6 is required for the C5-hydroxy... | ACCEPT | Summary: Ozeir et al. 2011; coq6 mutant is Q-deficient and is rescued by C5-hydroxylated 4-HB analogues. Core process. Supporting Evidence: PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. PMID:21944752 hydroxylated analogs of 4-hydroxybenzoic acid, such as vanillic acid or 3,4-dihydroxybenzoic acid, restore Q biosynthesis and respiration in a Saccharomyces cerevisiae coq6 mutant |
| GO:0006744 ubiquinone biosynthetic process | IMP PMID:9266513 Sensitivity to treatment with polyunsaturated fatty acids is... | ACCEPT | Summary: Poon et al. 1997; coq6 mutants fail to make Q and accumulate 3-hexaprenyl-4-hydroxybenzoate, the Coq6 substrate. Correct. Supporting Evidence: PMID:9266513 coq3, coq4, coq5, coq6, coq7, or coq8 genes were unable to produce Q and accumulated an early intermediated that corresponded to 3-hexaprenyl-4-hydroxybenzoic acid. |
| GO:0006744 ubiquinone biosynthetic process | NAS PMID:24406904 Coenzyme Q supplementation or over-expression of the yeast C... | ACCEPT | Summary: He et al. 2014 state Coq6 performs a ring hydroxylation of Q biosynthesis. Correct, redundant. Supporting Evidence: PMID:24406904 The other Coq polypeptides catalyze ring modification steps including O-methylation (Coq3), C-methylation (Coq5), or hydroxylation (Coq6 and Coq7). |
| GO:0006744 ubiquinone biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-862 membership. Coq6 catalyses a step of Q6 synthesis, so the process is correct even though one of the reactions YeastPathways assigns to it (C1 hydroxylation) is not. Supporting Evidence: PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. |
| GO:0008681 2-octaprenyl-6-methoxyphenol hydroxylase activity | ISA PMID:12721307 The Saccharomyces cerevisiae COQ6 gene encodes a mitochondri... | REMOVE | Summary: ISA to E. coli UbiH (P25534), the bacterial C1 hydroxylase of 2-octaprenyl-6-methoxyphenol, made by Gin et al. 2003 when Coq6 was only predicted to be "required for one or more steps". Later experimental work showed Coq6 acts exclusively at C5 (and C4-deamination), and the C1 steps in eukaryotes are performed by a COQ4-dependent oxidative decarboxylation, so 2-methoxy-6-polyprenylphenol is not a pathway intermediate. The term is also specific to octaprenyl/NADPH chemistry. Contradicted by later experimental evidence on the same protein. Supporting Evidence: PMID:12721307 Based on sequence homology to known proteins, we suggest that COQ6 encodes a flavin-dependent monooxygenase required for one or more steps in Q biosynthesis. PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. PMID:38295803 Here, we provide evidence that these two reactions occur in a single oxidative decarboxylation step catalyzed by COQ4. |
| GO:0008681 2-octaprenyl-6-methoxyphenol hydroxylase activity | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways PWY3O-19 assigns the C1 hydroxylation (2-hexaprenyl-6-methoxyphenol + NADPH + O2, EC 1.14.13.-) to Coq6 by analogy with UbiH. Contradicted for Coq6 (exclusive C5 hydroxylase) and the eukaryotic C1 chemistry is COQ4-dependent. Mis-assigned reaction in YeastPathways. Supporting Evidence: PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. PMID:38295803 Here, we provide evidence that these two reactions occur in a single oxidative decarboxylation step catalyzed by COQ4. |
| GO:0016491 oxidoreductase activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA to the generic oxidoreductase term from node PTN000350182. Correct but uninformative; the specific activity of Coq6 is known. Proposed replacements: 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity Supporting Evidence: PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. |
| GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR010971 (UbiH/COQ6) mapping to a high-level monooxygenase parent. Correct but uninformative. Proposed replacements: 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity Supporting Evidence: PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. PMID:21944752 the ferredoxin Yah1 and the ferredoxin reductase Arh1 may be the in vivo source of electrons for Coq6 |
| 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: UniRule UR000376533 transfer of the flavin-donor monooxygenase class. Coq6 is an FAD-containing monooxygenase, but its external electron donor is ferredoxin (Yah1), and the specific reaction term GO:0106364 sits under the iron-sulfur-donor class (GO:0016713), not GO:0016712. Replace with the specific activity. Proposed replacements: 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity Supporting Evidence: PMID:21944752 the ferredoxin Yah1 and the ferredoxin reductase Arh1 may be the in vivo source of electrons for Coq6 PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. |
| 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 | IMP PMID:21944752 Coenzyme Q biosynthesis: Coq6 is required for the C5-hydroxy... | MODIFY | Summary: Ozeir et al. 2011 established the C5-hydroxylase activity of Coq6, annotated at the time to this class-level term. The specific term GO:0106364 now exists (and is separately annotated from the same paper); it classifies the reaction under ferredoxin (iron-sulfur) donor chemistry, consistent with Yah1/Arh1 as the electron source. Proposed replacements: 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity Supporting Evidence: PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. PMID:21944752 the ferredoxin Yah1 and the ferredoxin reductase Arh1 may be the in vivo source of electrons for Coq6 |
| GO:0031314 extrinsic component of mitochondrial inner membrane | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule UR000376533 extrinsic inner membrane location; matches Gin et al. 2003 for yeast Coq6. Supporting Evidence: PMID:12721307 Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro IPR010971 mapping. Coq6 is an FAD-dependent monooxygenase (flavin prosthetic group); cofactor binding is correct but not a core function term. Supporting Evidence: PMID:26260787 We show here that the FAD-dependent monooxygenase Coq6, which is known to hydroxylate position C5, also deaminates position C4 in a reaction implicating molecular oxygen, as demonstrated with labeling experiments. file:yeast/COQ6/COQ6-uniprot.txt -!- FUNCTION: FAD-dependent monooxygenase required for two non-consecutive |
| GO:0071949 FAD binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro IPR002938 (FAD-binding domain) mapping. Correct cofactor binding; non-core. Supporting Evidence: PMID:26260787 We show here that the FAD-dependent monooxygenase Coq6, which is known to hydroxylate position C5, also deaminates position C4 in a reaction implicating molecular oxygen, as demonstrated with labeling experiments. |
| GO:0106364 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR000689, RHEA:20361, EC 1.14.15.45). Correct; core MF. Supporting Evidence: PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. |
| GO:0106364 4-hydroxy-3-all-trans-polyprenylbenzoate oxygenase activity | IMP PMID:21944752 Coenzyme Q biosynthesis: Coq6 is required for the C5-hydroxy... | ACCEPT | Summary: Ozeir et al. 2011 showed Coq6 is required exclusively for C5 hydroxylation of HHB to DHHB, with Yah1/Arh1 as electron donors, and that DHHB analogues bypass coq6. Core MF. Supporting Evidence: PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. PMID:21944752 the ferredoxin Yah1 and the ferredoxin reductase Arh1 may be the in vivo source of electrons for Coq6 PMID:21944752 hydroxylated analogs of 4-hydroxybenzoic acid, such as vanillic acid or 3,4-dihydroxybenzoic acid, restore Q biosynthesis and respiration in a Saccharomyces cerevisiae coq6 mutant |
| GO:0120538 2-methoxy-6-polyprenolphenol 4-hydroxylase activity | IEA GO_REF:0000120 | REMOVE | Summary: Rhea-based IEA (RHEA:81279, EC 1.14.15.46) from the HAMAP MF_03193 rule, which transfers a C1 (4-) hydroxylation of 2-methoxy-6-polyprenylphenol to Coq6 by similarity only. Ozeir et al. showed yeast Coq6 acts exclusively at C5, and Pelosi et al. 2024 showed the eukaryotic C1 decarboxylation and hydroxylation occur in one COQ4-dependent oxidative decarboxylation, so this substrate is not formed. Supporting Evidence: PMID:21944752 We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. PMID:38295803 Here, we provide evidence that these two reactions occur in a single oxidative decarboxylation step catalyzed by COQ4. |
| GO:0110142 ubiquinone biosynthesis complex | IDA PMID:24406904 Coenzyme Q supplementation or over-expression of the yeast C... | NEW | Summary: Coq6 is a member of the Coq4-organised CoQ synthome (He et al. 2014) and its stability depends on the other Coq proteins; human COQ6 already carries this CC term. Membership claim, not a process. Supporting Evidence: PMID:24406904 Hence, we propose that Coq4 may be a crucial component through which Coq3, Coq5, Coq6, Coq7, and Coq9 associate to form the CoQ-synthome. |
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Download this section (compressed HTML)Q: Should UniProt/HAMAP MF_03193 and YeastPathways PWY3O-19 drop the C1 hydroxylation (EC 1.14.15.46 / 1.14.13.-) from Coq6, given Ozeir 2011 and the COQ4 oxidative decarboxylation (Pelosi 2024)?
Q: Is there a GO term (or should one be requested) for the Coq6 C4-deamination of 3-hexaprenyl-4-aminobenzoate (RHEA:58392 and the following deamination), needed for Q6 synthesis from pABA?
Experiment: Reconstitute purified Coq6 with Arh1/Yah1/NADPH and test HHB, HAB and 2-methoxy-6-hexaprenylphenol as substrates to confirm that C1 hydroxylation is absent in vitro.
Flavin-dependent monooxygenase involved in ubiquinone biosynthesis; responsible for hydroxylation at position C5 and deamination at C4 during ubiquinone (Coenzyme Q) biosynthesis; localizes to matrix face of mitochondrial inner membrane in a large complex with other ubiquinone biosynthetic enzymes; human homolog COQ6 can complement yeast null mutant and is implicated in steroid-resistant nephrotic syndrome (SRNS)
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