COQ3 encodes the mitochondrial S-adenosyl-L-methionine-dependent O-methyltransferase of coenzyme Q10 biosynthesis, a member of the UbiG/COQ3 family of class I methyltransferases. After import via an N-terminal transit peptide it associates peripherally with the matrix face of the inner mitochondrial membrane as a subunit of the COQ complex (complex Q, with COQ4, COQ5, COQ6, COQ7 and COQ9). COQ3 catalyses two non-consecutive O-methylations of the benzoquinone ring: methylation of 3,4-dihydroxy-5-decaprenylbenzoate to 4-hydroxy-3-methoxy-5-decaprenylbenzoate early in ring modification, and the final methylation of 3-demethylubiquinol (or 3-demethylubiquinone) to ubiquinol-10 (ubiquinone-10). The reaction requires Mg2+, and COQ3 is phosphorylated by COQ8B in vitro. Human COQ3 restores CoQ synthesis in yeast coq3 null mutants, and its loss causes primary CoQ10 deficiency.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat... | REMOVE | Summary: Affinity-enrichment and cell-free co-expression mapping of the human CoQ biosynthetic complex (Floyd et al. 2016) detected COQ3 with COQ5. Reason: Bare protein binding is uninformative under the project protein-binding policy and is removed. Removal does not dispute the interaction: COQ3 association with the other COQ proteins is captured by the GO:0110142 ubiquinone biosynthesis complex row from the same paper. Supporting Evidence: PMID:27499296 many coexpression pairs between COQ3-7 and COQ9 were stabilized by direct interaction |
| GO:0005515 protein binding | IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat... | REMOVE | Summary: Affinity-enrichment and cell-free co-expression mapping of the human CoQ biosynthetic complex (Floyd et al. 2016) detected COQ3 with COQ7. Reason: Bare protein binding is uninformative under the project protein-binding policy and is removed. Removal does not dispute the interaction: COQ3 association with the other COQ proteins is captured by the GO:0110142 ubiquinone biosynthesis complex row from the same paper. Supporting Evidence: PMID:27499296 many coexpression pairs between COQ3-7 and COQ9 were stabilized by direct interaction |
| GO:0005515 protein binding | IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat... | REMOVE | Summary: Affinity-enrichment and cell-free co-expression mapping of the human CoQ biosynthetic complex (Floyd et al. 2016) detected COQ3 with COQ6. Reason: Bare protein binding is uninformative under the project protein-binding policy and is removed. Removal does not dispute the interaction: COQ3 association with the other COQ proteins is captured by the GO:0110142 ubiquinone biosynthesis complex row from the same paper. Supporting Evidence: PMID:27499296 many coexpression pairs between COQ3-7 and COQ9 were stabilized by direct interaction |
| GO:0005515 protein binding | IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat... | REMOVE | Summary: Affinity-enrichment and cell-free co-expression mapping of the human CoQ biosynthetic complex (Floyd et al. 2016) detected COQ3 with COQ4. Reason: Bare protein binding is uninformative under the project protein-binding policy and is removed. Removal does not dispute the interaction: COQ3 association with the other COQ proteins is captured by the GO:0110142 ubiquinone biosynthesis complex row from the same paper. Supporting Evidence: PMID:27499296 many coexpression pairs between COQ3-7 and COQ9 were stabilized by direct interaction |
| GO:0005515 protein binding | IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat... | REMOVE | Summary: Affinity-enrichment and cell-free co-expression mapping of the human CoQ biosynthetic complex (Floyd et al. 2016) detected COQ3 with NFS1. Reason: Bare protein binding is uninformative under the project protein-binding policy and is removed; the COQ3-NFS1 association from the interaction screen has no known functional consequence. Supporting Evidence: PMID:27499296 many coexpression pairs between COQ3-7 and COQ9 were stabilized by direct interaction |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary yeast two-hybrid interaction of COQ3 with PTPN9 (Luck et al. 2020). Reason: Bare protein binding from a proteome-scale Y2H screen with a non-mitochondrial partner; uninformative under the protein-binding policy and of no known functional relevance to the matrix-side O-methyltransferase. Supporting Evidence: PMID:32296183 yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary yeast two-hybrid interaction of COQ3 with TTPA (Luck et al. 2020). Reason: Bare protein binding from a proteome-scale Y2H screen with a non-mitochondrial partner; uninformative under the protein-binding policy and of no known functional relevance to the matrix-side O-methyltransferase. Supporting Evidence: PMID:32296183 yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary yeast two-hybrid interaction of COQ3 with SNX1 (Luck et al. 2020). Reason: Bare protein binding from a proteome-scale Y2H screen with a non-mitochondrial partner; uninformative under the protein-binding policy and of no known functional relevance to the matrix-side O-methyltransferase. Supporting Evidence: PMID:32296183 yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: HuRI binary yeast two-hybrid interaction of COQ3 with NDRG4 isoform 2 (Luck et al. 2020). Reason: Bare protein binding from a proteome-scale Y2H screen with a non-mitochondrial partner; uninformative under the protein-binding policy and of no known functional relevance to the matrix-side O-methyltransferase. Supporting Evidence: PMID:32296183 yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Detected in the high-confidence human mitochondrial proteome (MitoCoP). Reason: Root organelle term from organelle proteomics, which cannot resolve the sub-compartment; ACCEPT under the organelle policy. COQ3 carries a predicted mitochondrial transit peptide. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). file:human/COQ3/COQ3-uniprot.txt /note="Mitochondrion" |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA mitochondrion from the eukaryotic COQ3 node PTN000566263 (Arabidopsis, mouse, fission and budding yeast, human). Reason: PAINT places the mitochondrial location at the eukaryotic UbiG/COQ3 node (taxon:2759); human COQ3 is inside that clade and is itself one of the seeds, which marks experimental grounding, not circularity. The organelle claim holds; the inner-membrane rows give the sub-compartment. Supporting Evidence: file:human/COQ3/COQ3-uniprot.txt /note="Mitochondrion" PMID:28927698 The O-methylations are catalyzed by COQ3 in eukaryotes |
| GO:0005739 mitochondrion | IDA PMID:10777520 Isolation and functional expression of human COQ3, a gene en... | ACCEPT | Summary: Jonassen and Clarke (2000) cloned human COQ3 and expressed it in yeast coq3 mutants; UniProt and the IDA attribute mitochondrial localization to this work. Reason: The cached abstract does not describe the localization assay, but the claim is not in doubt (transit peptide, proteomics, HAMAP-supported inner-membrane location); the curator who read the full text is deferred to for this root organelle term. Supporting Evidence: PMID:10777520 When expressed in multicopy, the human construct rescued the growth of a yeast coq3 null mutant on a nonfermentable carbon source and restored coenzyme Q biosynthesis file:human/COQ3/COQ3-uniprot.txt /note="Mitochondrion" |
| GO:0005743 mitochondrial inner membrane | IDA PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat... | ACCEPT | Summary: UniProt cites Floyd et al. 2016 for the inner-membrane location of the human CoQ biosynthetic complex. Reason: Consistent with the matrix-side peripheral association of the COQ complex; the full text maps a membrane-associated COQ complex. The precise term GO:0031314 is also annotated. Supporting Evidence: file:human/COQ3/COQ3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:27499296 many coexpression pairs between COQ3-7 and COQ9 were stabilized by direct interaction |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping (SL-0168) of the curated inner-membrane location. Reason: The SubCell mapping agrees with the experimental row for the same term. Supporting Evidence: file:human/COQ3/COQ3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-2162186 | ACCEPT | Summary: Reactome TAS inner-membrane location from the reaction "COQ3 methylates DeMQ10H2" (R-HSA-2162186), in which COQ3 is modelled as a member of the membrane-associated COQ complex. Reason: COQ3 is a matrix-side peripheral inner-membrane protein of the COQ complex; the location is correct whichever complex reaction carries it. Supporting Evidence: Reactome:R-HSA-2162193 COQ3 is a membrane-associated protein file:human/COQ3/COQ3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-2162187 | ACCEPT | Summary: Reactome TAS inner-membrane location from the reaction "COQ6 hydroxylates DHB" (R-HSA-2162187), in which COQ3 is modelled as a member of the membrane-associated COQ complex. Reason: COQ3 is a matrix-side peripheral inner-membrane protein of the COQ complex; the location is correct whichever complex reaction carries it. Supporting Evidence: Reactome:R-HSA-2162193 COQ3 is a membrane-associated protein file:human/COQ3/COQ3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-2162188 | ACCEPT | Summary: Reactome TAS inner-membrane location from the reaction "COQ5 methylates MDMQ10H2" (R-HSA-2162188), in which COQ3 is modelled as a member of the membrane-associated COQ complex. Reason: COQ3 is a matrix-side peripheral inner-membrane protein of the COQ complex; the location is correct whichever complex reaction carries it. Supporting Evidence: Reactome:R-HSA-2162193 COQ3 is a membrane-associated protein file:human/COQ3/COQ3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-2162193 | ACCEPT | Summary: Reactome TAS inner-membrane location from the reaction "COQ3 methylates DHDB" (R-HSA-2162193), in which COQ3 is modelled as a member of the membrane-associated COQ complex. Reason: COQ3 is a matrix-side peripheral inner-membrane protein of the COQ complex; the location is correct whichever complex reaction carries it. Supporting Evidence: Reactome:R-HSA-2162193 COQ3 is a membrane-associated protein file:human/COQ3/COQ3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-2162194 | ACCEPT | Summary: Reactome TAS inner-membrane location from the reaction "COQ7:COQ9 octamer hydroxylates DMQ10H2" (R-HSA-2162194), in which COQ3 is modelled as a member of the membrane-associated COQ complex. Reason: COQ3 is a matrix-side peripheral inner-membrane protein of the COQ complex; the location is correct whichever complex reaction carries it. Supporting Evidence: Reactome:R-HSA-2162193 COQ3 is a membrane-associated protein file:human/COQ3/COQ3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-2162195 | ACCEPT | Summary: Reactome TAS inner-membrane location from the reaction "COQ4 decarboxylates MHDB" (R-HSA-2162195), in which COQ3 is modelled as a member of the membrane-associated COQ complex. Reason: COQ3 is a matrix-side peripheral inner-membrane protein of the COQ complex; the location is correct whichever complex reaction carries it. Supporting Evidence: Reactome:R-HSA-2162193 COQ3 is a membrane-associated protein file:human/COQ3/COQ3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of mitochondrial matrix from mouse Coq3. Reason: COQ3 is a peripheral protein on the matrix face of the inner membrane and APEX proximity labelling placed human COQ3 in the matrix; the matrix term is consistent with that topology, as in the human COQ5 review. Supporting Evidence: PMID:28927698 COQ3, COQ5, COQ6, COQ8A/B, and COQ9 were localized to the mitochondrial matrix via an “APEX” study file:human/COQ3/COQ3-uniprot.txt Matrix side |
| GO:0006071 glycerol metabolic process | IGI PMID:10777520 Isolation and functional expression of human COQ3, a gene en... | REMOVE | Summary: IGI from Jonassen and Clarke 2000: human COQ3 rescues growth of a yeast coq3 null mutant on a nonfermentable carbon source (glycerol). Reason: Growth on glycerol is a readout of restored respiration, which needs CoQ; it does not show that COQ3 participates in glycerol metabolism. The process term mistakes the growth medium for the function. Supporting Evidence: PMID:10777520 When expressed in multicopy, the human construct rescued the growth of a yeast coq3 null mutant on a nonfermentable carbon source and restored coenzyme Q biosynthesis |
| GO:0006744 ubiquinone biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA ubiquinone biosynthetic process from the eukaryotic COQ3 node PTN000566263, seeded by plant, fly, fission and budding yeast, rat, human and worm members. Reason: Core process. COQ3 catalyses both O-methylation steps of the CoQ head group; human COQ3 is itself a seed of the node. Supporting Evidence: PMID:28927698 The O-methylations are catalyzed by COQ3 in eukaryotes file:human/COQ3/COQ3-uniprot.txt O-methyltransferase required for two non-consecutive steps |
| GO:0006744 ubiquinone biosynthetic process | IDA PMID:38425362 In vitro construction of the COQ metabolon unveils the molec... | ACCEPT | Summary: Nicoll et al. 2024 reconstituted the COQ pathway in vitro, with COQ3 catalysing the C5 and C6 O-methylations, and produced CoQ1. Reason: Core process. The experiments used tetrapod ancestral COQ proteins (>75% identical to human), not the extant human protein; the activity is nevertheless consistent with the human enzyme assays of PMID:10777520, so the curator is deferred to. Supporting Evidence: PMID:38425362 formation of the O-methyl group at the C6 position, mediated by COQ7 and COQ3, producing the final product, CoQ1 PMID:38425362 Unless otherwise stated, all the experimental work was performed using the tetrapod ancestral COQ proteins PMID:38425362 They share >75% sequence identities with the corresponding extant human COQ proteins |
| GO:0006744 ubiquinone biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt combined IEA (InterPro IPR010233, UniRule, UniPathway, rat ortholog). Reason: Consistent with the experimental and IBA rows for the core process. Supporting Evidence: file:human/COQ3/COQ3-uniprot.txt O-methyltransferase required for two non-consecutive steps |
| GO:0006744 ubiquinone biosynthetic process | IGI PMID:10777520 Isolation and functional expression of human COQ3, a gene en... | ACCEPT | Summary: IGI: human COQ3 restores coenzyme Q biosynthesis in a yeast coq3 null mutant. Reason: Cross-species complementation of the CoQ defect by the human enzyme; core process. Supporting Evidence: PMID:10777520 When expressed in multicopy, the human construct rescued the growth of a yeast coq3 null mutant on a nonfermentable carbon source and restored coenzyme Q biosynthesis |
| GO:0006744 ubiquinone biosynthetic process | NAS PMID:28927698 Biochemistry of Mitochondrial Coenzyme Q Biosynthesis. | ACCEPT | Summary: NAS from the Stefely and Pagliarini review of CoQ biosynthesis. Reason: Review statement that COQ3 performs the eukaryotic O-methylations; consistent with experimental rows. Supporting Evidence: PMID:28927698 The O-methylations are catalyzed by COQ3 in eukaryotes |
| GO:0006744 ubiquinone biosynthetic process | TAS Reactome:R-HSA-2142789 | ACCEPT | Summary: Reactome TAS: COQ3 participates in the ubiquinol biosynthesis pathway. Reason: Consistent with the experimental rows for the core process. Supporting Evidence: Reactome:R-HSA-2162193 Mitochondrial O-methyltransferase COQ3 converts 3,4-dihydroxy-5-decaprenylbenzoic acid (DHDB) to 3-methoxy-4-hydroxy-5-decaprenylbenzoic acid (MHDB) |
| GO:0008171 O-methyltransferase activity | IGI PMID:10777520 Isolation and functional expression of human COQ3, a gene en... | MODIFY | Summary: IGI from PMID:10777520 for generic O-methyltransferase activity; the paper shows activity of human COQ3 with farnesylated analogues of the CoQ intermediates. Reason: Correct but general: the specific O-methyltransferase activities are supported and already carried by the gene, so both are listed. Proposed replacements: polyprenyldihydroxybenzoate methyltransferase activity 3-demethylubiquinol 3-O-methyltransferase activity Supporting Evidence: PMID:10777520 the human enzyme is active with all three substrates tested file:human/COQ3/COQ3-uniprot.txt O-methyltransferase required for two non-consecutive steps |
| GO:0010420 polyprenyldihydroxybenzoate methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000566263 seeded by Arabidopsis, budding yeast, human and worm members. Reason: Core activity: the first (C5) O-methylation of 3,4-dihydroxy-5-polyprenylbenzoate. Human COQ3 is inside the eukaryotic clade and one of the seeds. Supporting Evidence: file:human/COQ3/COQ3-uniprot.txt O-methyltransferase required for two non-consecutive steps Reactome:R-HSA-2162193 Mitochondrial O-methyltransferase COQ3 converts 3,4-dihydroxy-5-decaprenylbenzoic acid (DHDB) to 3-methoxy-4-hydroxy-5-decaprenylbenzoic acid (MHDB) |
| GO:0010420 polyprenyldihydroxybenzoate methyltransferase activity | IDA PMID:38425362 In vitro construction of the COQ metabolon unveils the molec... | ACCEPT | Summary: Nicoll et al. 2024: COQ3 consumes the DHDB analogue (compound 2) with SAM in a Mg2+-dependent reaction. Reason: Core activity. Measured on the tetrapod ancestral COQ3 (>75% identical to human); consistent with the human-enzyme activity of PMID:10777520, so the curator is deferred to. Supporting Evidence: PMID:38425362 Substrate depletion was observed in the presence of COQ3 and S-adenosyl methionine (SAM) PMID:38425362 Unless otherwise stated, all the experimental work was performed using the tetrapod ancestral COQ proteins PMID:10777520 the human enzyme is active with all three substrates tested |
| GO:0010420 polyprenyldihydroxybenzoate methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt combined IEA (InterPro, RHEA:44492, EC 2.1.1.114, UniRule). Reason: Correct; consistent with the IBA and IDA rows for the same term. Supporting Evidence: file:human/COQ3/COQ3-uniprot.txt O-methyltransferase required for two non-consecutive steps |
| GO:0010420 polyprenyldihydroxybenzoate methyltransferase activity | TAS Reactome:R-HSA-2162193 | ACCEPT | Summary: Reactome TAS reaction "COQ3 methylates DHDB". Reason: Correct; consistent with the experimental rows for the same term. Supporting Evidence: Reactome:R-HSA-2162193 Mitochondrial O-methyltransferase COQ3 converts 3,4-dihydroxy-5-decaprenylbenzoic acid (DHDB) to 3-methoxy-4-hydroxy-5-decaprenylbenzoic acid (MHDB) |
| GO:0031314 extrinsic component of mitochondrial inner membrane | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule (HAMAP MF_03190) extrinsic component of mitochondrial inner membrane. Reason: Peripheral, matrix-side inner-membrane association is the topology of COQ3 family members (fractionation of yeast Coq3) and of the human COQ complex; the most precise location supported. Supporting Evidence: file:human/COQ3/COQ3-uniprot.txt Matrix side file:human/COQ3/COQ3-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0061542 3-demethylubiquinol 3-O-methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000566267 (deuterostome node) seeded by human COQ3. Reason: Core activity: the final O-methylation, 3-demethylubiquinol to ubiquinol. The node is seeded by the human protein itself, so the IBA records that the activity is inherited within the clade. Supporting Evidence: file:human/COQ3/COQ3-uniprot.txt O-methyltransferase required for two non-consecutive steps Reactome:R-HSA-2162186 Mitochondrial COQ3 is an O-methyltransferase required in the reaction to convert 3-demethylubiquinol-10 (DeMQ10H2) to ubiquinol-10 (Q10H2) |
| GO:0061542 3-demethylubiquinol 3-O-methyltransferase activity | IDA PMID:10777520 Isolation and functional expression of human COQ3, a gene en... | ACCEPT | Summary: Jonassen and Clarke 2000: purified human COQ3 methylates demethyl-Q analogues. Reason: Core activity shown with the human enzyme. Supporting Evidence: PMID:10777520 the human enzyme is active with all three substrates tested |
| GO:0061542 3-demethylubiquinol 3-O-methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt combined IEA (RHEA:44412, EC 2.1.1.64). Reason: Correct; consistent with the IDA row for the same term. Supporting Evidence: file:human/COQ3/COQ3-uniprot.txt O-methyltransferase required for two non-consecutive steps |
| GO:0061542 3-demethylubiquinol 3-O-methyltransferase activity | TAS Reactome:R-HSA-2162186 | ACCEPT | Summary: Reactome TAS reaction "COQ3 methylates DeMQ10H2". Reason: Correct; consistent with the IDA row for the same term. Supporting Evidence: Reactome:R-HSA-2162186 Mitochondrial COQ3 is an O-methyltransferase required in the reaction to convert 3-demethylubiquinol-10 (DeMQ10H2) to ubiquinol-10 (Q10H2) |
| GO:0110142 ubiquinone biosynthesis complex | IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat... | ACCEPT | Summary: Floyd et al. 2016 showed that COQ3 forms direct pairwise interactions with COQ4-7 and COQ9 in cell-free co-expression, defining a human CoQ biosynthetic complex. Reason: COQ3 is a subunit of the COQ complex; the GO:0110142 definition names it. Supporting Evidence: PMID:27499296 many coexpression pairs between COQ3-7 and COQ9 were stabilized by direct interaction |
| GO:0120537 3-demethylubiquinone 3-O-methyltransferase activity | IDA PMID:38425362 In vitro construction of the COQ metabolon unveils the molec... | ACCEPT | Summary: Nicoll et al. 2024: in the reconstituted pathway COQ3 with COQ7:COQ9 forms the C6 O-methyl group to give CoQ1 (quinone form). Reason: Core activity. The quinone-level reaction is the one assayed in vitro; measured on the ancestral COQ3, consistent with the human enzyme data, and matches the yeast COQ3 review. Supporting Evidence: PMID:38425362 formation of the O-methyl group at the C6 position, mediated by COQ7 and COQ3, producing the final product, CoQ1 PMID:38425362 Unless otherwise stated, all the experimental work was performed using the tetrapod ancestral COQ proteins |
| GO:0120537 3-demethylubiquinone 3-O-methyltransferase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea2GO mapping of RHEA:81215 (3-demethylubiquinone methylation) from UniProt. Reason: Consistent with the IDA row for the same term. Supporting Evidence: file:human/COQ3/COQ3-uniprot.txt Reaction=a 3-demethylubiquinone + S-adenosyl-L-methionine = a |
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Download this section (compressed HTML)Q: Does phosphorylation of COQ3 by COQ8B, observed with ancestral proteins in vitro (PMID:38425362), occur on extant human COQ3 in mitochondria, and does it regulate the COQ6-COQ3 C5 modification?
Experiment: Assay purified extant human COQ3 (not the ancestral reconstruction) with DHDB and demethyl-CoQ analogues, with and without COQ8B-mediated phosphorylation, to confirm the kinetics measured on the ancestral enzyme.
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