COQ1 encodes the mitochondrial hexaprenyl diphosphate synthase of the FPP/GGPP synthase family (PTHR12001). It synthesises all-trans-hexaprenyl diphosphate (C30), the isoprenoid side chain of coenzyme Q6, by sequential head-to-tail condensation of isopentenyl diphosphate onto an allylic prenyl diphosphate primer, using the conserved aspartate-rich (DDxxD) motifs. Coq2p then transfers this chain to 4-hydroxybenzoate. Coq1p is a peripheral protein on the matrix side of the inner mitochondrial membrane. coq1 mutants lack hexaprenyl pyrophosphate synthetase activity and CoQ6 and are respiratory-deficient. Expressing heterologous prenyl diphosphate synthases of different chain-length specificity in a coq1 null strain yields Q5 to Q10, which are all functional to varying degrees, though Q6 is optimal. Loss of Coq1p, or of its lipid product, destabilises other Coq polypeptides (Coq3, Coq4, Coq6), and orthologous synthases restore their levels, consistent with a role for polyprenylated intermediates in assembling the CoQ biosynthetic complex. Unlike the heterotetrameric mammalian PDSS1/PDSS2 and S. pombe Dps1/Dlp1 enzymes, no second subunit has been described for S. cerevisiae Coq1p.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000010 heptaprenyl diphosphate synthase activity | IMP PMID:9708911 Biological significance of the side chain length of ubiquino... | MODIFY | Summary: IMP from Okada et al. 1998, who used a coq1 mutant "defective for hexaprenyl diphosphate synthesis" as a host for heterologous prenyl diphosphate synthases (producing UQ-5 to UQ-10). The mutant phenotype supports a prenyl diphosphate synthase activity for Coq1p, but GO:0000010 heptaprenyl diphosphate synthase activity specifies a C35 product, and S. cerevisiae Coq1p makes the C30 hexaprenyl chain of CoQ6. The term was probably chosen via its synonym "trans-hexaprenyltranstransferase activity" (the old EC 2.5.1.30 name), which names a C35 product. The correct chain-length term is hexaprenyl diphosphate synthase. Reason: Coq1p synthesises hexaprenyl (C30), not heptaprenyl (C35), diphosphate; the native ubiquinone of S. cerevisiae is Q6. GO:0036423 is the hexaprenyl-diphosphate synthase term used for COQ1 in the ubiquinone module. Its FPP-primer specificity is the generally assumed one but has not been tested directly for yeast Coq1p. Proposed replacements: hexaprenyl-diphosphate synthase ((2E,6E)-farnesyl-diphosphate specific) activity Supporting Evidence: PMID:9708911 different types of prenyl diphosphate synthases were expressed in a S. cerevisiae COQ1 mutant defective for hexaprenyl diphosphate synthesis PMID:9708911 we found that the original species of UQ (in this case UQ-6) had maximum functionality PMID:2198286 both glycerol growth and hexaprenyl pyrophosphate synthetase activity were restored |
| GO:0004659 prenyltransferase activity | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA from PTN000243362, the broad trans-prenyl diphosphate synthase node of PTHR12001 (sources include S. japonicus Dps1/Dlp1 orthologs). The node placement is sound and the inherited activity is correct for Coq1p at this level of generality; the specific activity (hexaprenyl diphosphate synthase, GO:0036423) is captured in core_functions. Supporting Evidence: PMID:2198286 both glycerol growth and hexaprenyl pyrophosphate synthetase activity were restored |
| GO:0004659 prenyltransferase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO mapping from IPR000092 (polyprenyl synthetase) to generic prenyltransferase activity. Correct for Coq1p at this level of generality; the specific hexaprenyl diphosphate synthase activity (GO:0036423) is captured in core_functions. Supporting Evidence: PMID:2198286 both glycerol growth and hexaprenyl pyrophosphate synthetase activity were restored |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: IPI from the Gavin et al. 2006 genome-wide TAP-MS complex survey. The "protein binding" term records an unspecified co-purification and conveys no function (removal does not imply the interaction is false); the physiologically relevant associations of Coq1p are with the CoQ biosynthetic machinery on the matrix face of the inner membrane, and IntAct lists the chaperone Ssa2 as a partner. Reason: Uninformative protein binding term from high-throughput affinity purification; no specific binding function is established. Supporting Evidence: PMID:16429126 Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Detected in high-throughput proteomics of purified yeast mitochondria; consistent with the experimentally established matrix-side inner-membrane location. Supporting Evidence: PMID:14576278 The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS. PMID:15548532 Antibodies that recognize Coq1p, a hexaprenyl diphosphate synthase, were generated and used to determine that Coq1p is peripherally associated with the inner membrane on the matrix side. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Detected in high-throughput proteomics of purified yeast mitochondria; consistent with the experimentally established matrix-side inner-membrane location. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS PMID:15548532 Antibodies that recognize Coq1p, a hexaprenyl diphosphate synthase, were generated and used to determine that Coq1p is peripherally associated with the inner membrane on the matrix side. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Detected in high-throughput proteomics of purified yeast mitochondria; consistent with the experimentally established matrix-side inner-membrane location. Supporting Evidence: PMID:24769239 we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria PMID:15548532 Antibodies that recognize Coq1p, a hexaprenyl diphosphate synthase, were generated and used to determine that Coq1p is peripherally associated with the inner membrane on the matrix side. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA is_active_in mitochondrion from PTN000243365 (eukaryotic CoQ polyprenyl diphosphate synthases). Correct; Coq1p acts on the matrix side of the inner membrane (GO:0031314 more precise). Supporting Evidence: PMID:15548532 Antibodies that recognize Coq1p, a hexaprenyl diphosphate synthase, were generated and used to determine that Coq1p is peripherally associated with the inner membrane on the matrix side. |
| GO:0005739 mitochondrion | IMP PMID:10760477 Genetic evidence for a multi-subunit complex in the O-methyl... | ACCEPT | Summary: IMP (is_active_in) from Hsu et al. 2000, who isolated mitochondria from each coq null mutant (coq1 included) to assay Coq3p; mitochondrial function of Coq1p is implied by the coq1 mitochondrial phenotype. Mitochondrial location is independently established (Gin & Clarke 2004), so the curator annotation is accepted. Supporting Evidence: PMID:10760477 Mitochondria have been isolated from each member of the yeast coq mutant collection PMID:15548532 Antibodies that recognize Coq1p, a hexaprenyl diphosphate synthase, were generated and used to determine that Coq1p is peripherally associated with the inner membrane on the matrix side. |
| GO:0005739 mitochondrion | IMP PMID:10760477 Genetic evidence for a multi-subunit complex in the O-methyl... | ACCEPT | Summary: IMP (located_in) from Hsu et al. 2000, who isolated mitochondria from each coq null mutant (coq1 included) to assay Coq3p; mitochondrial function of Coq1p is implied by the coq1 mitochondrial phenotype. Mitochondrial location is independently established (Gin & Clarke 2004), so the curator annotation is accepted. Supporting Evidence: PMID:10760477 Mitochondria have been isolated from each member of the yeast coq mutant collection PMID:15548532 Antibodies that recognize Coq1p, a hexaprenyl diphosphate synthase, were generated and used to determine that Coq1p is peripherally associated with the inner membrane on the matrix side. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0168, inner membrane, peripheral, matrix side). Correct; GO:0031314 is more precise. Supporting Evidence: file:yeast/COQ1/COQ1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane PMID:15548532 Antibodies that recognize Coq1p, a hexaprenyl diphosphate synthase, were generated and used to determine that Coq1p is peripherally associated with the inner membrane on the matrix side. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA is_active_in cytosol from PWY3O-862 (superpathway of ubiquinone biosynthesis); the GO-CAM conversion placed ubiquinone pathway activities in the cytosol by default. Coq1p is peripherally associated with the matrix side of the inner mitochondrial membrane; cytosol is wrong. Reason: Experimentally, Coq1p acts on the matrix side of the mitochondrial inner membrane. Supporting Evidence: PMID:15548532 Antibodies that recognize Coq1p, a hexaprenyl diphosphate synthase, were generated and used to determine that Coq1p is peripherally associated with the inner membrane on the matrix side. |
| GO:0006744 ubiquinone biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000243365 (eukaryotic CoQ side-chain polyprenyl diphosphate synthases). Correct core process. Supporting Evidence: PMID:2198286 In yeast these reactions are catalyzed by hexaprenyl pyrophosphate synthetase and PHB:polyprenyltransferase, respectively. |
| GO:0006744 ubiquinone biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00232 (ubiquinone biosynthesis) mapping. Correct. Supporting Evidence: PMID:2198286 In yeast these reactions are catalyzed by hexaprenyl pyrophosphate synthetase and PHB:polyprenyltransferase, respectively. |
| GO:0006744 ubiquinone biosynthetic process | IMP PMID:9708911 Biological significance of the side chain length of ubiquino... | ACCEPT | Summary: Okada et al. used the coq1 mutant, which cannot make the hexaprenyl side chain and therefore lacks UQ-6, and restored UQ synthesis with heterologous prenyl diphosphate synthases. Coq1p builds the isoprenoid tail of CoQ6, so it performs a step of ubiquinone biosynthesis (core). Supporting Evidence: PMID:9708911 different types of prenyl diphosphate synthases were expressed in a S. cerevisiae COQ1 mutant defective for hexaprenyl diphosphate synthesis PMID:9708911 we found that the original species of UQ (in this case UQ-6) had maximum functionality |
| GO:0006744 ubiquinone biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from HEXPPSYN-PWY-2 (hexaprenyl diphosphate biosynthesis). Coq1p makes the hexaprenyl diphosphate tail transferred by Coq2p to 4-hydroxybenzoate, the first committed steps of CoQ6 synthesis; correct. Supporting Evidence: PMID:2198286 In yeast these reactions are catalyzed by hexaprenyl pyrophosphate synthetase and PHB:polyprenyltransferase, respectively. |
| GO:0006744 ubiquinone biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from PWY3O-862 (superpathway of ubiquinone biosynthesis). Coq1p makes the hexaprenyl diphosphate tail transferred by Coq2p to 4-hydroxybenzoate, the first committed steps of CoQ6 synthesis; correct. Supporting Evidence: PMID:2198286 In yeast these reactions are catalyzed by hexaprenyl pyrophosphate synthetase and PHB:polyprenyltransferase, respectively. |
| GO:0008299 isoprenoid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000243362 (trans-prenyl diphosphate synthase node). Hexaprenyl diphosphate synthesis is an isoprenoid biosynthetic process; correct but general. Supporting Evidence: file:yeast/COQ1/COQ1-uniprot.txt FUNCTION: Assembly of polyisoprenoid side chains. The polyprenyl |
| GO:0008299 isoprenoid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from IPR000092 (polyprenyl synthetase). Correct but general. Supporting Evidence: file:yeast/COQ1/COQ1-uniprot.txt FUNCTION: Assembly of polyisoprenoid side chains. The polyprenyl |
| GO:0031314 extrinsic component of mitochondrial inner membrane | IDA PMID:15548532 Genetic evidence for a multi-subunit complex in coenzyme Q b... | ACCEPT | Summary: Gin & Clarke raised Coq1p antibodies and showed by submitochondrial fractionation that Coq1p is peripherally associated with the inner membrane on the matrix side. Precise core location. Supporting Evidence: PMID:15548532 Antibodies that recognize Coq1p, a hexaprenyl diphosphate synthase, were generated and used to determine that Coq1p is peripherally associated with the inner membrane on the matrix side. |
| GO:0032476 polyprenyl diphosphate synthase complex | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA part_of polyprenyl diphosphate synthase complex from PTN000243365. In mammals (PDSS1/PDSS2) and S. pombe (Dps1/Dlp1) the CoQ side-chain synthase is a heterotetramer of two related subunits, and the IBA is seeded from such heteromeric enzymes. S. cerevisiae Coq1p acts as the sole hexaprenyl diphosphate synthase, and no Dlp1/PDSS2-type partner subunit has been described; trans-prenyl diphosphate synthases are nevertheless obligate oligomers, so a (likely homomeric) complex is plausible. The GO term definition does not require heteromers. Kept as non-core pending direct evidence of yeast Coq1p quaternary structure. Supporting Evidence: PMID:15548532 Yeast Deltacoq1 mutants harboring diverse Coq1 orthologs from prokaryotic species produce distinct sizes of polyprenyl diphosphate and hence distinct isoforms of Q including Q(7), Q(8), Q(9), or Q(10) |
| GO:1901663 quinone biosynthetic process | IEA GO_REF:0000117 | MODIFY | Summary: ARBA rule ARBA00026910 mapping to quinone biosynthetic process. Coq1p synthesises the polyprenyl tail of ubiquinone; the specific process GO:0006744 is already annotated, and Coq1p does not act on the quinone ring. Reason: Ubiquinone biosynthetic process is the precise process for Coq1p. Proposed replacements: ubiquinone biosynthetic process Supporting Evidence: PMID:2198286 In yeast these reactions are catalyzed by hexaprenyl pyrophosphate synthetase and PHB:polyprenyltransferase, respectively. |
Loading supporting content…
Download this section (compressed HTML)Q: What allylic primer does Coq1p use in vivo: (2E,6E)-farnesyl diphosphate from Erg20p, or geranylgeranyl diphosphate from Bts1p (as drawn in YeastPathways)?
Q: Is S. cerevisiae Coq1p a homo-oligomer, or does it associate with an as-yet-unidentified partner analogous to S. pombe Dlp1 or human PDSS2?
Experiment: Purify recombinant mature Coq1p, determine its oligomeric state (SEC-MALS), and measure product chain length and kinetics with DMAPP, GPP, FPP and GGPP primers plus 14C-IPP.
Hypothesis: Coq1p is a homo-oligomeric hexaprenyl diphosphate synthase that preferentially uses FPP as primer
Type: in vitro enzymology / biophysics
Hexaprenyl pyrophosphate synthetase; catalyzes the first step in ubiquinone (coenzyme Q) biosynthesis
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)