COQ3 (YOL096C) encodes the S-adenosyl-L-methionine-dependent O-methyltransferase of coenzyme Q6 (ubiquinone) biosynthesis in Saccharomyces cerevisiae, a member of the UbiG/COQ3 family of class I SAM-dependent methyltransferases. A single Coq3 polypeptide catalyses both, non-consecutive, ring O-methylation steps of the pathway: methylation of 3,4-dihydroxy-5-hexaprenylbenzoate (DHHB) to 4-hydroxy-3-methoxy-5-hexaprenylbenzoate (EC 2.1.1.114), and the final step, methylation of 3-demethylubiquinol-6 (demethyl-Q6) to ubiquinol-6 (EC 2.1.1.64). The protein is imported into mitochondria and is peripherally associated with the matrix face of the inner membrane, where it is a member of the multi-subunit Coq polypeptide complex (CoQ synthome) organised around Coq4 together with Coq5, Coq6, Coq7 and Coq9; its stability and association with the complex depend on the other Coq proteins and on the Coq8 kinase-like protein, which promotes its phosphorylation. coq3 null mutants lack Q6 and cannot grow on non-fermentable carbon sources.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Sickmann et al. 2003 identified Coq3 in the proteome of highly purified mitochondria. Consistent with the precise inner-membrane (matrix side) localisation shown by Poon et al. 1999. Supporting Evidence: PMID:14576278 The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS. PMID:10419476 antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Reinders et al. 2006 PROMITO mitochondrial proteome detected Coq3. Correct, though less specific than inner membrane. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified PMID:10419476 antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Renvoise et al. 2014 quantitative mitochondrial (phospho)proteome detected Coq3; consistent with its known mitochondrial location and with Coq8-dependent phosphorylation of Coq3. Supporting Evidence: PMID:24769239 overall quantitative proteomic and phosphoproteomic study of isolated mitochondria PMID:10419476 antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the UbiG/COQ3 node PTN000566263 (with/from includes human COQ3, mouse Coq3, S. pombe Coq3 and SGD Coq3 itself). Eukaryotic COQ3 orthologues are mitochondrial; correct for yeast Coq3. Supporting Evidence: PMID:10419476 antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria |
| GO:0005739 mitochondrion | IDA PMID:10760477 Genetic evidence for a multi-subunit complex in the O-methyl... | ACCEPT | Summary: Hsu et al. 2000 measured Coq3 O-methyltransferase activity and Coq3 polypeptide in isolated mitochondria from wild type and each coq mutant. Supports mitochondrial location. Supporting Evidence: PMID:10760477 Each of these mitochondrial preparations has been analyzed for COQ3-encoded O-methyltransferase activity and steady state levels of Coq3 polypeptide. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:10419476 Yeast and rat Coq3 and Escherichia coli UbiG polypeptides ca... | ACCEPT | Summary: Poon et al. 1999 showed by sub-mitochondrial fractionation with anti-Coq3 antibodies that Coq3 is peripherally associated with the matrix side of the inner membrane. Correct location for the enzyme's site of action. Supporting Evidence: PMID:10419476 antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria |
| GO:0005743 mitochondrial inner membrane | IDA PMID:24406904 Coenzyme Q supplementation or over-expression of the yeast C... | ACCEPT | Summary: He et al. 2014 (Coq8 over-expression study) analysed Coq polypeptides in mitochondria and restates that Coq3 is a matrix-side peripheral inner membrane protein. 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, Mitochondrion inner membrane), itself based on PMID:10419476. Correct. Supporting Evidence: file:yeast/COQ3/COQ3-uniprot.txt -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000255|HAMAP- PMID:10419476 antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA (PWY3O-19, ubiquinol-6 biosynthesis from 4-hydroxybenzoate) assigning the pathway-default cytosol compartment to Coq3. Wrong for this protein; Coq3 acts on the matrix face of the mitochondrial inner membrane and Q biosynthesis is carried out within mitochondria. Supporting Evidence: PMID:10419476 antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria PMID:10419476 Q biosynthesis is carried out within the matrix compartment of yeast mitochondria |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA (PWY3O-862, superpathway of ubiquinone biosynthesis) assigning cytosol. Same error as the PWY3O-19 row; Coq3 is a mitochondrial matrix-side inner membrane enzyme. Supporting Evidence: PMID:10419476 antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria PMID:10419476 Q biosynthesis is carried out within the matrix compartment of yeast mitochondria |
| GO:0006744 ubiquinone biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from UbiG/COQ3 node PTN000566263; the family function is conserved from UbiG to COQ3, and yeast Coq3 has direct experimental support. Supporting Evidence: PMID:10419476 The results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes PMID:1885593 This gene restores both coenzyme Q synthesis in the mutant strain and the ability to grow on media containing glycerol, a nonfermentable substrate. |
| GO:0006744 ubiquinone biosynthetic process | IDA PMID:10419476 Yeast and rat Coq3 and Escherichia coli UbiG polypeptides ca... | ACCEPT | Summary: Poon et al. 1999 showed in vitro that yeast mitochondria/Coq3 methylate both Q-pathway intermediates. Core process. Supporting Evidence: PMID:10419476 The results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes PMID:10419476 Both yeast and rat Coq3p recognize the demethyl-Q(3) precursor as a substrate. |
| GO:0006744 ubiquinone biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR010233 UbiG family, UniRule UR000375836, UniPathway UPA00232). Correct for Coq3. Supporting Evidence: file:yeast/COQ3/COQ3-uniprot.txt -!- FUNCTION: O-methyltransferase required for two non-consecutive steps |
| GO:0006744 ubiquinone biosynthetic process | IMP PMID:1885593 Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolati... | ACCEPT | Summary: Clarke et al. 1991 cloned COQ3 by complementation of a coq3 Q-deficient mutant; the gene restores Q synthesis and growth on glycerol. Supporting Evidence: PMID:1885593 This gene restores both coenzyme Q synthesis in the mutant strain and the ability to grow on media containing glycerol, a nonfermentable substrate. PMID:1885593 establishing that the COQ3 locus encodes the DHHB methyltransferase structural gene |
| GO:0006744 ubiquinone biosynthetic process | NAS PMID:24406904 Coenzyme Q supplementation or over-expression of the yeast C... | ACCEPT | Summary: He et al. 2014 states Coq3 performs the O-methylation steps of Q biosynthesis. Correct, though redundant with stronger IDA/IMP evidence. 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 (superpathway of ubiquinone biosynthesis) membership. Coq3 really does catalyse two steps of this pathway, so the process term is correct. Supporting Evidence: PMID:10419476 The results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes |
| GO:0010420 polyprenyldihydroxybenzoate methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for the DHHB O-methyltransferase activity (EC 2.1.1.114) from node PTN000566263. Correct; conserved family activity, experimentally established for yeast Coq3. Supporting Evidence: PMID:1885593 establishing that the COQ3 locus encodes the DHHB methyltransferase structural gene PMID:10419476 The results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes |
| GO:0010420 polyprenyldihydroxybenzoate methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR010233, RHEA:14121, EC 2.1.1.114, UniRule). Correct. Supporting Evidence: PMID:1885593 establishing that the COQ3 locus encodes the DHHB methyltransferase structural gene |
| GO:0010420 polyprenyldihydroxybenzoate methyltransferase activity | IMP PMID:1885593 Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolati... | ACCEPT | Summary: Clarke et al. 1991 identified COQ3 as the structural gene for DHHB methyltransferase by complementation and gene replacement (abstract-only cache; consistent with all later work). Core MF. Supporting Evidence: PMID:1885593 establishing that the COQ3 locus encodes the DHHB methyltransferase structural gene PMID:1885593 This gene restores both coenzyme Q synthesis in the mutant strain and the ability to grow on media containing glycerol, a nonfermentable substrate. |
| GO:0010420 polyprenyldihydroxybenzoate methyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-19 reaction DHHB + SAM -> 4-hydroxy-3-methoxy-5-hexaprenylbenzoate (EC 2.1.1.114) assigned to Coq3. Correct. Supporting Evidence: PMID:10419476 The results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes |
| GO:0010420 polyprenyldihydroxybenzoate methyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-862 (superpathway) assignment of the same EC 2.1.1.114 reaction. Correct. Supporting Evidence: PMID:10419476 The results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes |
| GO:0031314 extrinsic component of mitochondrial inner membrane | IDA PMID:10419476 Yeast and rat Coq3 and Escherichia coli UbiG polypeptides ca... | ACCEPT | Summary: Poon et al. 1999 found Coq3 peripherally associated with the matrix side of the inner membrane, which is exactly this term. Supporting Evidence: PMID:10419476 antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria |
| GO:0031314 extrinsic component of mitochondrial inner membrane | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule UR000375836 transfer of extrinsic inner membrane location; matches the experimental finding for yeast Coq3. Supporting Evidence: PMID:10419476 antibodies to yeast Coq3p were used to determine that the Coq3 polypeptide is peripherally associated with the matrix-side of the inner membrane of yeast mitochondria |
| GO:0061542 3-demethylubiquinol 3-O-methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR010233, RHEA:44400, EC 2.1.1.64, UniRule) for the final demethylubiquinol O-methylation. Correct for Coq3. Supporting Evidence: PMID:10419476 Both yeast and rat Coq3p recognize the demethyl-Q(3) precursor as a substrate. PMID:10419476 The results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes |
| GO:0061542 3-demethylubiquinol 3-O-methyltransferase activity | IMP PMID:10419476 Yeast and rat Coq3 and Escherichia coli UbiG polypeptides ca... | ACCEPT | Summary: Poon et al. 1999 showed that the second O-methylation (demethyl-Q3 to Q3, farnesylated analogues) depends on Coq3 in yeast mitochondria. Core MF (second of the two Coq3 steps). Supporting Evidence: PMID:10419476 Both yeast and rat Coq3p recognize the demethyl-Q(3) precursor as a substrate. PMID:10419476 The results indicate that one O-methyltransferase catalyzes both steps in Q biosynthesis in eukaryotes and prokaryotes |
| GO:0061542 3-demethylubiquinol 3-O-methyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-19 reaction 3-demethylubiquinol-6 + SAM -> ubiquinol-6 (EC 2.1.1.64) assigned to Coq3. Correct. Supporting Evidence: PMID:10419476 Both yeast and rat Coq3p recognize the demethyl-Q(3) precursor as a substrate. |
| GO:0061542 3-demethylubiquinol 3-O-methyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-862 superpathway assignment of the EC 2.1.1.64 step. Correct. Supporting Evidence: PMID:10419476 Both yeast and rat Coq3p recognize the demethyl-Q(3) precursor as a substrate. |
| GO:0120537 3-demethylubiquinone 3-O-methyltransferase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based IEA (RHEA:81215, 3-demethylubiquinone + SAM -> ubiquinone), from the HAMAP MF_03190 rule. It describes the same final O-methylation with the substrate drawn in the quinone rather than quinol redox state. Which redox form is the physiological substrate is not settled; UniProt records both reactions for Coq3, so the term is acceptable alongside GO:0061542. Supporting Evidence: file:yeast/COQ3/COQ3-uniprot.txt catalyzes the last step of ubiquinone biosynthesis by mediating PMID:10419476 Both yeast and rat Coq3p recognize the demethyl-Q(3) precursor as a substrate. |
| GO:0110142 ubiquinone biosynthesis complex | IDA PMID:24406904 Coenzyme Q supplementation or over-expression of the yeast C... | NEW | Summary: Coq3 O-methyltransferase activity co-elutes with Coq4, Coq5, Coq6, Coq7 and Coq9 in high molecular mass complexes (gel filtration, BN-PAGE), and He et al. 2014 place Coq3 as a member of the Coq4-organised CoQ synthome; earlier genetic data showed Coq3 stability depends on the other Coq proteins. Human COQ5/COQ6 orthologues already carry this term. Cellular-component membership, not a process claim. Supporting Evidence: PMID:24406904 In such extracts the O-methyltransferase activity of Coq3 co-eluted with several of the other Coq polypeptides as high molecular mass complexes 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. PMID:10760477 These data are consistent with the involvement of the Coq polypeptides (or the Q-intermediates formed by the Coq polypeptides) in a multi-subunit complex. |
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Download this section (compressed HTML)Q: Is the physiological substrate of the final Coq3 step 3-demethylubiquinol-6 or 3-demethylubiquinone-6, and how is the redox state of the intermediate controlled in the CoQ synthome?
Q: SGD/GOA lack a cellular-component annotation of yeast Coq3 to GO:0110142 ubiquinone biosynthesis complex, although human COQ5/COQ6 carry it and yeast Coq3 co-purifies with Coq4 and co-elutes with the CoQ synthome; should this be added?
Experiment: Reconstitute purified Coq3 with DHHB and with demethyl-Q6 in both redox states, in the presence and absence of Coq4/Coq9, to determine substrate preference and whether complex membership stimulates activity.
O-methyltransferase; catalyzes two different O-methylation steps in ubiquinone (Coenzyme Q) biosynthesis; component of a mitochondrial ubiquinone-synthesizing complex; phosphoprotein
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