COQ8 (ABC1, YGL119W) encodes a mitochondrial UbiB-family protein kinase-like (PKL) protein required for coenzyme Q6 biosynthesis. Coq8 is imported and processed in mitochondria and associates peripherally with the matrix face of the inner membrane. coq8 null mutants lack CoQ and accumulate 3-hexaprenyl-4-hydroxybenzoate, and Coq8 overexpression stabilizes the CoQ synthome (Coq3-Coq7, Coq9) in other coq mutants. Coq8 was long considered a protein kinase because phosphorylation of Coq3, Coq5 and Coq7 depends on it. Purified Coq8, however, has no protein kinase activity in trans and autophosphorylates only in cis, in a way that is dispensable in vivo. It has an ADP-selective nucleotide pocket, ATPase activity that depends on its KxGQ motif, and binds membranes and lipid CoQ intermediates. How the ATPase and lipid-binding activities are coupled to synthome assembly and to the CoQ ring modifications is still unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004672 protein kinase activity | IDA NOT PMID:27499294 Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of ... | ACCEPT | Summary: NOT annotation: Stefely et al. purified mature yeast Coq8 and showed it does not phosphorylate myelin basic protein or COQ proteins in trans; autophosphorylation occurs only in cis. Reason: The negative statement is directly supported by in vitro assays with the yeast protein. Supporting Evidence: PMID:27499294 Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans PMID:27499294 neither WT nor A197G,K134H Coq8NΞ41 catalyzed phosphorylation of myelin basic protein or mixtures of COQ proteins in trans |
| GO:0004672 protein kinase activity | IMP PMID:22593570 Overexpression of the Coq8 kinase in Saccharomyces cerevisia... | REMOVE | Summary: Xie et al. 2012 inferred protein kinase activity because kinase-motif mutations abolished the stabilizing effect of Coq8 overexpression. Those motifs form the nucleotide pocket that is also required for ATPase activity, and direct assays later showed Coq8 lacks trans protein kinase activity (PMID:27499294; NOT annotation from UniProt). Reason: Genuinely contradicted by later biochemistry on the same yeast protein; the phenotype is explained by loss of the ATPase/nucleotide-binding function rather than protein kinase activity. Supporting Evidence: PMID:22593570 we provide evidence that the kinase activity is essential for the stabilizing effect of Coq8 PMID:27499294 Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans PMID:27499294 neither WT nor A197G,K134H Coq8NΞ41 catalyzed phosphorylation of myelin basic protein or mixtures of COQ proteins in trans |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Coq8 detected in purified mitochondria by high-throughput proteomics (PMID:14576278). Reason: Root organelle term from whole-organelle proteomics, which cannot resolve the sub-compartment; ACCEPT under the organelle policy. Targeted fractionation (PMID:21296186) gives the matrix-side inner-membrane location recorded on separate rows. Supporting Evidence: PMID:11279158 Abc1/Coq8p localizes to the mitochondria, and is proteolytically processed upon import |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Coq8 detected in purified mitochondria by high-throughput proteomics (PMID:16823961). Reason: Root organelle term from whole-organelle proteomics, which cannot resolve the sub-compartment; ACCEPT under the organelle policy. Targeted fractionation (PMID:21296186) gives the matrix-side inner-membrane location recorded on separate rows. Supporting Evidence: PMID:11279158 Abc1/Coq8p localizes to the mitochondria, and is proteolytically processed upon import |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Coq8 detected in purified mitochondria by high-throughput proteomics (PMID:24769239). Reason: Root organelle term from whole-organelle proteomics, which cannot resolve the sub-compartment; ACCEPT under the organelle policy. Targeted fractionation (PMID:21296186) gives the matrix-side inner-membrane location recorded on separate rows. Supporting Evidence: PMID:11279158 Abc1/Coq8p localizes to the mitochondria, and is proteolytically processed upon import |
| GO:0005739 mitochondrion | IDA PMID:11279158 A defect in coenzyme Q biosynthesis is responsible for the r... | ACCEPT | Summary: Do et al. showed Abc1/Coq8p is imported into mitochondria and processed. Reason: Direct import evidence on the yeast protein; root organelle term from an assay that does not resolve the sub-compartment. Supporting Evidence: PMID:11279158 Abc1/Coq8p localizes to the mitochondria, and is proteolytically processed upon import |
| GO:0005743 mitochondrial inner membrane | EXP PMID:11279158 A defect in coenzyme Q biosynthesis is responsible for the r... | ACCEPT | Summary: UniProt inner membrane location citing Do et al. 2001 (mitochondrial import and processing). Reason: Inner-membrane association (matrix side) is confirmed by sub-fractionation in PMID:21296186. Supporting Evidence: PMID:11279158 Abc1/Coq8p localizes to the mitochondria, and is proteolytically processed upon import PMID:21296186 Coq8p is a peripherally associated membrane protein located on the matrix side of the inner membrane |
| GO:0005743 mitochondrial inner membrane | EXP PMID:18801050 Ubiquinone biosynthesis in Saccharomyces cerevisiae: the mol... | ACCEPT | Summary: Tauche et al. found Coq8p to behave as a matrix protein or one associated with the inner membrane. Reason: Consistent with peripheral matrix-side inner membrane association. Supporting Evidence: PMID:18801050 Localization studies identify Coq8p as a soluble mitochondrial protein, with characteristics of a protein of the matrix or associated with the inner mitochondrial membrane |
| GO:0005743 mitochondrial inner membrane | EXP PMID:21296186 Expression of the human atypical kinase ADCK3 rescues coenzy... | ACCEPT | Summary: Sub-fractionation of mitoplasts showed Coq8p peripherally associated with the matrix side of the inner membrane. Reason: Direct evidence; the more precise GO:0031314 (extrinsic component of mitochondrial inner membrane) is added below as NEW from the same paper. Supporting Evidence: PMID:21296186 Coq8p is a peripherally associated membrane protein located on the matrix side of the inner membrane |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0168). Reason: The SubCell mapping agrees with the experimental rows for the same term. Supporting Evidence: PMID:21296186 Coq8p is a peripherally associated membrane protein located on the matrix side of the inner membrane |
| GO:0005759 mitochondrial matrix | IDA PMID:18801050 Ubiquinone biosynthesis in Saccharomyces cerevisiae: the mol... | ACCEPT | Summary: Tauche et al. found Coq8p soluble with characteristics of a matrix protein. Reason: Tauche et al. found Coq8p behaving as a matrix protein or one associated with the inner membrane, and the later mitoplast sub-fractionation (PMID:21296186) resolved it as peripheral on the matrix side of the inner membrane. A matrix-facing peripheral protein is within the matrix compartment, so the curator's IDA is accepted; the membrane-associated location is the more precise one. Supporting Evidence: PMID:18801050 Localization studies identify Coq8p as a soluble mitochondrial protein, with characteristics of a protein of the matrix or associated with the inner mitochondrial membrane |
| GO:0006468 protein phosphorylation | IDA NOT PMID:27499294 Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of ... | ACCEPT | Summary: NOT annotation: Coq8 does not phosphorylate proteins in trans; the Coq8-dependent phosphorylation of Coq proteins is probably indirect. Reason: Supported by direct in vitro data on the yeast protein; Coq8-dependent phosphorylation of Coq3, Coq5 and Coq7 (PMID:21296186) is therefore likely indirect. Supporting Evidence: PMID:27499294 neither WT nor A197G,K134H Coq8NΞ41 catalyzed phosphorylation of myelin basic protein or mixtures of COQ proteins in trans PMID:27499294 mutating Coq8NΞ41 autophosphorylation sites did not inhibit respiratory yeast growth |
| GO:0006744 ubiquinone biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the UbiB/COQ8 family node supported by yeast, human, plant and fly members. Reason: Core process. Yeast Coq8 is in the COQ8 clade under PTN000059692 and is itself one of the experimental seeds. Coq8 contributes ATPase and lipid-binding activity that the synthome needs, so it does part of the work rather than only being required. Supporting Evidence: PMID:11279158 abc1/coq8 null mutants are defective in Q biosynthesis and accumulate 3-hexaprenyl-4-hydroxybenzoic acid as the predominant intermediate |
| GO:0006744 ubiquinone biosynthetic process | IDA PMID:25152161 Molecular characterization of the human COQ5 C-methyltransfe... | ACCEPT | Summary: In the human COQ5 study, Coq8 overexpression stabilized the yeast CoQ synthome so that human COQ5 could restore Q6 synthesis in coq5 null cells. Reason: Consistent with the established role of Coq8 in CoQ synthome stability; the process is correct. Supporting Evidence: PMID:25152161 over-expression of COQ8 in coq5 null mutants permits the human COQ5 homolog to partially restore coq5 mutant growth on respiratory media and Q6 content |
| GO:0006744 ubiquinone biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway (UPA00232) mapping to ubiquinone biosynthesis. Reason: Consistent with the experimental and IBA rows for the core process. Supporting Evidence: PMID:11279158 abc1/coq8 null mutants are defective in Q biosynthesis and accumulate 3-hexaprenyl-4-hydroxybenzoic acid as the predominant intermediate |
| GO:0006744 ubiquinone biosynthetic process | IMP PMID:11279158 A defect in coenzyme Q biosynthesis is responsible for the r... | ACCEPT | Summary: abc1/coq8 null mutants lack Q and accumulate 3-hexaprenyl-4-hydroxybenzoate. Reason: Direct genetic evidence on the yeast gene. Supporting Evidence: PMID:11279158 abc1/coq8 null mutants are defective in Q biosynthesis and accumulate 3-hexaprenyl-4-hydroxybenzoic acid as the predominant intermediate |
| GO:0006744 ubiquinone biosynthetic process | IMP PMID:25498144 Mitochondrial ADCK3 employs an atypical protein kinase-like ... | ACCEPT | Summary: Structure-guided Coq8p nucleotide-pocket and UbiB-motif mutants failed to rescue coq8Ξ respiratory growth and CoQ production. Reason: Direct genetic evidence linking the ATP-binding fold to CoQ biosynthesis. Supporting Evidence: PMID:25498144 We then expressed Coq8p variants in coq8Ξ yeast, which exhibit a respiratory growth defect on non-fermentable carbon sources caused by CoQ deficiency |
| GO:0008289 lipid binding | IDA PMID:27499294 Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of ... | ACCEPT | Summary: Recombinant Coq8 binds liposomes and co-purifies with lipid CoQ intermediates. Reason: Experimentally demonstrated lipid binding; one of the two biochemical activities identified for Coq8. Supporting Evidence: PMID:27499294 COQ8ANΞ250 and Coq8NΞ41 bind to liposomes PMID:27499294 Coq8p Binds Lipid CoQ Intermediates |
| GO:0008289 lipid binding | IMP PMID:27499294 Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of ... | ACCEPT | Summary: Mutational analysis in the same study links Coq8 lipid association to its function. Reason: Supported; the same paper's mutants link lipid association to function, consistent with the IDA row for the same term. Supporting Evidence: PMID:27499294 Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates |
| GO:0016301 kinase activity | IDA PMID:27499294 Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of ... | MARK AS OVER ANNOTATED | Summary: Coq8 autophosphorylates in cis in vitro (enhanced by A-rich loop or KxGQ mutations), but the autophosphorylation sites are dispensable in vivo and Coq8 has no trans protein kinase activity. Reason: Real but non-physiological in vitro activity: Coq8 autophosphorylates only in cis, mostly when the A-rich loop or KxGQ motif is mutated, the autophosphorylation sites are dispensable for respiratory growth, and there is no trans kinase activity. Under the promiscuous-activity tiers this is in vitro activity that does not reflect the protein's function, so the term over-states it. ATP hydrolysis (accepted) is the activity that tracks function. The human COQ8A review treats the same IDA rows as over-statements of kinase function (MODIFY/MARK_AS_OVER_ANNOTATED). Supporting Evidence: PMID:27499294 mutating Coq8NΞ41 autophosphorylation sites did not inhibit respiratory yeast growth PMID:27499294 Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans |
| GO:0016310 phosphorylation | IDA PMID:27499294 Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of ... | MARK AS OVER ANNOTATED | Summary: Phosphorylation (process) from the in vitro cis-autophosphorylation of Coq8. Reason: Autophosphorylation is dispensable for function in vivo and Coq8 does not phosphorylate other proteins; a phosphorylation process annotation overstates its role. Supporting Evidence: PMID:27499294 mutating Coq8NΞ41 autophosphorylation sites did not inhibit respiratory yeast growth |
| GO:0016887 ATP hydrolysis activity | IDA PMID:27499294 Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of ... | ACCEPT | Summary: Purified mature yeast Coq8 hydrolyses ATP; activity depends on the UbiB-specific KxGQ motif. Reason: Experimentally demonstrated activity that correlates with in vivo function (K134H abolishes both ATPase and CoQ production). Supporting Evidence: PMID:27499294 WT Coq8NΞ41 has ATPase activity PMID:27499294 Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates |
| GO:0016887 ATP hydrolysis activity | IMP PMID:27499294 Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of ... | ACCEPT | Summary: KxGQ (K134H) and D365N mutants lose ATPase activity and fail to support CoQ biosynthesis. Reason: Mutational data link the ATPase to in vivo function; consistent with the IDA row for the same term. Supporting Evidence: PMID:27499294 Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates |
| GO:0031314 extrinsic component of mitochondrial inner membrane | IDA PMID:21296186 Expression of the human atypical kinase ADCK3 rescues coenzy... | NEW | Summary: Mitoplast sub-fractionation shows Coq8p peripherally associated with the matrix side of the inner membrane; GOA carries only the parent term and the matrix term. Reason: Direct evidence for the precise location, shared with the other CoQ-synthome proteins. Supporting Evidence: PMID:21296186 Coq8p is a peripherally associated membrane protein located on the matrix side of the inner membrane |
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Download this section (compressed HTML)ATPase required for ubiquinone biosynthesis and respiratory growth; maintains levels of CoQ biosynthetic proteins; binds to CoQ biosynthesis intermediates; UbiB protein kinase-like family member that lacks canonical protein kinase activity; similar to prokaryotic proteins involved in ubiquinone biosynthesis; human homolog ADCK3 complements a coq8 null, is associated with CoQ and respiratory-chain deficiencies, and is mutated in autosomal-recessive cerebellar ataxia type 2
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