coq8

UniProt ID: Q92338
Organism: Schizosaccharomyces pombe 972h-
Review Status: COMPLETE
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Gene Description

coq8 (abc1) encodes the fission yeast Coq8 protein, a UbiB/ADCK-family atypical kinase-like protein in mitochondria, where its orthologs are peripheral proteins on the matrix side of the inner membrane within the CoQ biosynthetic complex. By homology with S. cerevisiae Coq8 and human COQ8A/B, it is an ATPase that binds CoQ intermediates and supports assembly and activity of the complex; whether it phosphorylates proteins or lipids in vivo is unresolved. coq8 mutants make no CoQ10, are respiration deficient, need antioxidants on minimal medium and overproduce sulfide; S. cerevisiae ABC1/COQ8 rescues the mutant and human COQ8A rescues it partially.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004672 protein kinase activity
TAS
PMID:38425362
In vitro construction of the COQ metabolon unveils the molec...
MARK AS OVER ANNOTATED
Summary: TAS citing the in vitro COQ metabolon reconstruction, in which a reconstructed animal COQ8B phosphorylated COQ3 and showed only basal ATPase activity. COQ8-family UbiB proteins are atypical kinase-like ATPases whose physiological substrate is unresolved, and protein kinase activity has not been tested for S. pombe Coq8.
Reason: PomBase TAS (PMID:38425362). The cited paper does show protein phosphorylation (COQ3 by animal COQ8B, in vitro), so the term is not baseless. But this is real in vitro activity of unknown physiological relevance, from an animal protein, not S. pombe. UniProt's curated function (by similarity to human COQ8A/COQ8B) records that the substrate specificity is unclear, with protein-kinase and small-molecule or lipid-kinase models both proposed. Asserting protein kinase activity for S. pombe Coq8 therefore over-reaches the evidence. The human COQ8B review keeps the IDA row from the same paper as non-core because the assay was on that protein; here the statement is transferred to a protein never assayed, so MARK_AS_OVER_ANNOTATED. Yeast Coq8 shows ATPase but not trans protein kinase activity (PMID:27499294).
Supporting Evidence:
file:SCHPO/coq8/coq8-uniprot.txt
Its substrate specificity is still unclear: may act as a protein kinase that mediates phosphorylation of coq3 (By similarity).
file:SCHPO/coq8/coq8-uniprot.txt
acts as a small molecule kinase, possibly a lipid kinase that phosphorylates a prenyl lipid in the ubiquinone biosynthesis pathway, as suggested by its ability to bind coenzyme Q lipid intermediates (By similarity).
PMID:38425362
COQ3, but not COQ6, is phosphorylated by COQ8B at multiple sites
PMID:38425362
We observed a basal unspecific ATPase activity
GO:0005739 mitochondrion
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ...
ACCEPT
Summary: ORFeome YFP screen: mitochondrion.
Reason: PomBase HDA from the ORFeome YFP screen. Hayashi et al. state that Coq8 was not among the proteins localised in that screen (PMID:24911838), so the provenance of this HDA cannot be checked from the cached abstract; the mitochondrial location itself is established by Coq8-GFP (PMID:24911838). Accepted on the location, without overruling the curator on the dataset; a question is recorded.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein
PMID:24911838
These results are consistent with those of a previous study [44] that examined the localization of 4,431 S. pombe proteins, although Coq8 was not included.
PMID:24911838
The Dps1, Ppt1/Coq2, Coq3, Coq4, Coq5, Coq6, Coq7, Coq8, and Coq9 GFP fusion proteins also localized to the mitochondria
GO:0005739 mitochondrion
IDA
PMID:24911838
Functional conservation of coenzyme Q biosynthetic genes amo...
ACCEPT
Summary: Mitochondrial localisation of the tagged protein.
Reason: Coq8-GFP expressed in the corresponding deletion strain localises to MitoTracker-stained mitochondria (PMID:24911838). Whole-organelle co-staining: ACCEPT at the root organelle term.
Supporting Evidence:
PMID:24911838
The Dps1, Ppt1/Coq2, Coq3, Coq4, Coq5, Coq6, Coq7, Coq8, and Coq9 GFP fusion proteins also localized to the mitochondria
PMID:24911838
The results presented here demonstrate that all of the S. pombe Coq proteins localize to mitochondria, indicating that CoQ biosynthesis occurs in these cellular compartments.
GO:0005739 mitochondrion
IEA
GO_REF:0000044
ACCEPT
Summary: UniProt/ARBA location mapping; consistent.
Reason: UniProt SubCell mapping (GO_REF:0000044). Mitochondrial location is shown on the target: a Coq8-GFP fusion co-localised with MitoTracker-stained mitochondria (PMID:24911838), which UniProt curates as experimental. Root organelle term kept.
Supporting Evidence:
PMID:24911838
The Dps1, Ppt1/Coq2, Coq3, Coq4, Coq5, Coq6, Coq7, Coq8, and Coq9 GFP fusion proteins also localized to the mitochondria
file:SCHPO/coq8/coq8-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:24911838}.
GO:0006744 ubiquinone biosynthetic process
EXP
PMID:8668131
Cloning by functional complementation, and inactivation, of ...
ACCEPT
Summary: abc1Sp/coq8 complements the S. cerevisiae abc1 (coq8) mutant (PMID:8668131).
Reason: The S. pombe cDNA was cloned by complementing the respiratory defect of S. cerevisiae abc1, whose product is the CoQ-pathway Coq8 (PMID:8668131), and the S. pombe disruption is rescued by S. cerevisiae ABC1. Cross-species complementation of a CoQ-deficient mutant supports the process; consistent with the IMP rows. Core process.
Supporting Evidence:
PMID:8668131
By functional complementation of a S. cerevisiae abc1(-) mutant, we have cloned a Schizosaccharomyces pombe cDNA, whose predicted product is 50% identical to the Abc1 protein.
PMID:8668131
Inactivation of the abc1Sp gene by homologous gene replacement causes a respiratory deficiency which is efficiently rescued by the expression of the S. cerevisiae ABC1 gene.
GO:0006744 ubiquinone biosynthetic process
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT inference; ubiquinone biosynthesis step.
Reason: IBA from PAINT node PTN000059692 (PTHR43851, GO_REF:0000033), of which coq8 is a seed. Shown on the target: the S. pombe abc1Sp/coq8 defective strain makes no UQ-10 (PMID:14695938), and UniProt curates the ubiquinone biosynthesis pathway with experimental evidence (PMID:24911838). The IBA adds that the role is inherited across the COQ8/ADCK family.
Supporting Evidence:
PMID:14695938
We show here that the abc1Sp defective strain did not produce UQ-10 and could not grow on minimal medium.
file:SCHPO/coq8/coq8-uniprot.txt
PATHWAY: Cofactor biosynthesis; ubiquinone biosynthesis.
GO:0006744 ubiquinone biosynthetic process
IEA
GO_REF:0000041
ACCEPT
Summary: Mapping; consistent.
Reason: UniPathway mapping (GO_REF:0000041). Same claim as the IMP, EXP and IBA rows: the S. pombe abc1Sp/coq8 defective strain makes no UQ-10 (PMID:14695938), and UniProt curates the pathway with experimental evidence.
Supporting Evidence:
PMID:14695938
We show here that the abc1Sp defective strain did not produce UQ-10 and could not grow on minimal medium.
file:SCHPO/coq8/coq8-uniprot.txt
PATHWAY: Cofactor biosynthesis; ubiquinone biosynthesis.
GO:0006744 ubiquinone biosynthetic process
IMP
PMID:14695938
Pleiotropic phenotypes of fission yeast defective in ubiquin...
ACCEPT
Summary: abc1Sp/coq8 mutants make no UQ-10.
Reason: The abc1Sp/coq8 defective strain makes no UQ-10 and shows the CoQ-deficient phenotypes (PMID:14695938). Coq8 acts within the CoQ synthome as a UbiB-family ATPase (by homology), so it contributes to the work of the process rather than only being required for it. Core process.
Supporting Evidence:
PMID:14695938
We show here that the abc1Sp defective strain did not produce UQ-10 and could not grow on minimal medium.
GO:0006744 ubiquinone biosynthetic process
IMP
PMID:24911838
Functional conservation of coenzyme Q biosynthetic genes amo...
ACCEPT
Summary: abc1Sp/coq8 mutants make no UQ-10.
Reason: The coq8 deletion lacks CoQ10, and S. pombe coq8 fully and human COQ8A/ADCK3 partly restore it (PMID:24911838). Core process.
Supporting Evidence:
PMID:24911838
Similarly, CoQ10 production by the S. pombe Ξ”coq8 strain was fully recovered by expression of S. pombe coq8 but only moderately recovered by expression of HsCOQ8/ADCK3 (Figure 7C).
PMID:24911838
Here, we expand these findings by identifying ten genes (dps1, dlp1, ppt1, and coq3-9) that are required for CoQ synthesis.
GO:0099616 extrinsic component of matrix side of mitochondrial inner membrane
ISO
GO_REF:0000024
ACCEPT
Summary: Peripheral component on the matrix side of the inner membrane, where the CoQ synthome assembles.
Reason: PomBase ISO from S. cerevisiae Coq8 (GO_REF:0000024). ISO transfer from S. cerevisiae Coq8 (SGD:S000003087). The sub-compartment evidence is the ortholog's: Coq8p fractionates as a peripheral membrane protein on the matrix side of the inner membrane (PMID:21296186, S. cerevisiae). In S. pombe only mitochondrial localisation is shown (Coq8-GFP, PMID:24911838); the matrix-side placement is accepted as a well-grounded ortholog inference, consistent with the CoQ synthome being matrix-facing.
Supporting Evidence:
PMID:21296186
The results show that Coq8p is a peripherally associated membrane protein located on the matrix side of the inner membrane
file:SCHPO/coq8/coq8-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:24911838}.
GO:0016887 ATP hydrolysis activity
ISS
PMID:27499294
Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of ...
NEW
Summary: ATPase activity of the UbiB-family Coq8 proteins, shown for S. cerevisiae Coq8 and inferred for S. pombe Coq8.
Reason: S. cerevisiae Coq8 hydrolyses ATP in vitro, an activity enhanced by the UbiB-specific KxGQ motif, while trans protein kinase activity is not detected (PMID:27499294); human COQ8A/B carry the same activity, and the human COQ8B and S. cerevisiae COQ8 reviews make it the core function. S. pombe Coq8 is a UbiB/ADCK-family member and human COQ8A/ADCK3 partially complements the S. pombe deletion (PMID:24911838). No S. pombe ATPase assay exists, so the row is by sequence similarity (ISS); it matches the module's Coq8 annoton (GO:0016887). No GO process is added.
Supporting Evidence:
PMID:27499294
WT Coq8NΞ”41 has ATPase activity and an A197G mutation, which enhances MgATP binding in vitro, increased the ATPase activity (Figures 4A and S4A–S4C).
file:SCHPO/coq8/coq8-uniprot.txt
Belongs to the protein kinase superfamily. ADCK protein kinase family.
PMID:24911838
Similarly, CoQ10 production by the S. pombe Ξ”coq8 strain was fully recovered by expression of S. pombe coq8 but only moderately recovered by expression of HsCOQ8/ADCK3 (Figure 7C).

Core Functions

UbiB-family atypical kinase-like ATPase of the CoQ synthome, needed for CoQ10 synthesis on the matrix face of the mitochondrial inner membrane.

Supporting Evidence:
  • PMID:14695938
    We show here that the abc1Sp defective strain did not produce UQ-10 and could not grow on minimal medium.
  • PMID:24911838
    Similarly, CoQ10 production by the S. pombe Ξ”coq8 strain was fully recovered by expression of S. pombe coq8 but only moderately recovered by expression of HsCOQ8/ADCK3 (Figure 7C).
  • PMID:27499294
    WT Coq8NΞ”41 has ATPase activity and an A197G mutation, which enhances MgATP binding in vitro, increased the ATPase activity (Figures 4A and S4A–S4C).
  • PMID:24911838
    The Dps1, Ppt1/Coq2, Coq3, Coq4, Coq5, Coq6, Coq7, Coq8, and Coq9 GFP fusion proteins also localized to the mitochondria

References

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Suggested Questions for Experts

Q: Does S. pombe Coq8 have the lipid-stimulated ATPase activity of S. cerevisiae Coq8, and does it phosphorylate any Coq protein in vivo?

Q: PomBase lists a coq8 mitochondrion HDA from the ORFeome screen (PMID:16823372), but Hayashi et al. (PMID:24911838) state that Coq8 was not included in that screen; which dataset does the HDA come from?

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Notes

(coq8-notes.md)

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