COQ9

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006744 ubiquinone biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred role in ubiquinone (CoQ) biosynthesis, fully concordant with the experimentally established, essential role of human COQ9 in CoQ10 biosynthesis and conserved across the COQ9 orthologous family. Reason: Represents a core, well-supported biological process for this gene; consistent with the experimental IDA/ISS annotations to the same term. Supporting Evidence: PMID:38425362 COQ9 has been shown to facilitate COQ7 activity in vivo
GO:0008289 lipid binding	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred lipid binding, concordant with the experimentally demonstrated lipid-binding molecular function of COQ9 (crystallized with bound phosphatidylethanolamine; associates with multiple lipid species including CoQ). Reason: Core molecular function of this non-catalytic protein; matches the experimental IDA lipid-binding annotation. Supporting Evidence: PMID:25339443 multiple lipid species, including CoQ itself
GO:0005743 mitochondrial inner membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred localization to the mitochondrial inner membrane, consistent with COQ9 acting on the matrix face of the inner membrane as part of the CoQ synthome and associating with cardiolipin-rich membranes. Reason: Correct compartment; matches experimental (ComplexPortal IDA) and Reactome TAS inner-membrane annotations.
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation from UniProt subcellular-location mapping. COQ9 is a well-established mitochondrial protein. Reason: Accurate but general organelle assignment; the more specific inner-membrane localization is captured by other annotations.
GO:0006744 ubiquinone biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (multi-method) annotation to ubiquinone biosynthetic process, redundant with the experimental and phylogenetic annotations to the same term. Reason: Correct core process; well-supported by experimental evidence.
GO:0008289 lipid binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation of lipid binding based on the COQ9 family signature (IPR012762), redundant with and confirmed by the experimental IDA lipid-binding annotation. Reason: Correct molecular function, supported by direct experimental evidence.
GO:0005515 protein binding	IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a mitochondrial protein-interaction mapping study. The partners recorded here include genuine CoQ-complex members (COQ5, COQ7, COQ8A) as well as a non-CoQ partner (ACSF2). The specific COQ7 interaction is captured functionally elsewhere; the bare term itself conveys no molecular function. Reason: GO:0005515 without a specific partner/function is uninformative; per policy an IPI protein-binding annotation is marked as over-annotated rather than removed.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" derived from a high-throughput binary (Y2H) interactome map (HuRI). The recorded partners (e.g. ADIPOQ, BMP10, CCL4L2, ALDH18A1) are not biologically meaningful CoQ-pathway interactors and largely reflect assay noise. Reason: Uninformative bare protein-binding term from a high-throughput screen; marked as over-annotated per policy (not removed).
GO:0005743 mitochondrial inner membrane	IDA PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	ACCEPT	Summary: Direct experimental localization to the mitochondrial inner membrane (ComplexPortal, from the mitochondrial protein interaction mapping study), consistent with COQ9's role in the inner-membrane-associated CoQ synthome. Reason: Experimentally supported localization to the correct compartment.
GO:0006744 ubiquinone biosynthetic process	NAS PMID:28927698 Biochemistry of Mitochondrial Coenzyme Q Biosynthesis.	ACCEPT	Summary: Author statement (ComplexPortal) placing COQ9 in the terminal-stage CoQ biosynthetic complex ("complex Q", COQ3-COQ9), consistent with the experimental evidence for its role in CoQ biosynthesis. Reason: Correct core process; corroborated by direct experimental annotations. Supporting Evidence: PMID:28927698 Complex Q is thought to contain proteins required for the terminal stage of CoQ biosynthesis (COQ3–COQ9)
GO:0110142 ubiquinone biosynthesis complex	IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	ACCEPT	Summary: COQ9 is a component of the ubiquinone biosynthesis complex (CoQ synthome / complex Q), demonstrated by co-purification/interaction with other COQ proteins. This is a core aspect of COQ9 biology. Reason: Well-supported membership in the CoQ biosynthetic complex; captures the accessory subunit role of this non-catalytic protein.
GO:0005739 mitochondrion	IDA PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	ACCEPT	Summary: Direct experimental evidence of mitochondrial localization/activity, consistent with COQ9's established mitochondrial function. Reason: Correct organelle; more specific inner-membrane localization captured elsewhere.
GO:0006744 ubiquinone biosynthetic process	IDA PMID:38425362 In vitro construction of the COQ metabolon unveils the molec...	ACCEPT	Summary: Direct experimental evidence from in vitro reconstruction of the animal COQ metabolon that COQ9 participates in CoQ biosynthesis by facilitating COQ7 activity (increased COQ7 catalytic efficiency ~1.5-fold when COQ9 is added). Reason: Strong experimental support for a core biological process; represents a defining function of the gene. Supporting Evidence: PMID:38425362 addition of COQ9 increased catalytic efficiency by 1.5-fold, substantiating its role for COQ7 function
GO:0019840 isoprenoid binding	IDA PMID:38425362 In vitro construction of the COQ metabolon unveils the molec...	ACCEPT	Summary: Direct experimental evidence that COQ9 binds isoprenoid (aromatic isoprene) CoQ intermediates. This lipophilic-intermediate binding underlies its substrate-presentation role toward COQ7. Reason: Specific, experimentally supported molecular function of this lipid-binding protein; more informative than the general lipid-binding term.
GO:0005515 protein binding	IPI PMID:30661980 An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzy...	KEEP AS NON CORE	Summary: IPI protein-binding annotation whose recorded partner is COQ7 (Q99807), the functionally central COQ9 interactor. The interaction is real and biologically important (COQ9 presents substrate to COQ7), but the bare "protein binding" term itself carries no molecular-function content; the meaningful biology is captured by the lipid/isoprenoid-binding, complex-membership and CoQ-biosynthesis annotations. Reason: Genuine, specific COQ7 interaction (never removed per policy), but retained as non-core because bare GO:0005515 is uninformative as a molecular function. Supporting Evidence: PMID:30661980 identify a molecular interface between COQ9 and the hydroxylase
GO:0006744 ubiquinone biosynthetic process	IDA PMID:30661980 An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzy...	ACCEPT	Summary: Direct experimental evidence that COQ9's custom lipid-binding properties promote eukaryotic CoQ biosynthesis by accessing membrane-embedded CoQ intermediates and presenting them to CoQ enzymes. Reason: Core biological process with strong experimental support. Supporting Evidence: PMID:30661980 presents intermediates directly to CoQ
GO:0019840 isoprenoid binding	IDA PMID:30661980 An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzy...	ACCEPT	Summary: Direct experimental evidence (structures 6AWL/6DEW) that COQ9 repurposes the bacterial TetR fold to bind aromatic isoprenes with high specificity, including CoQ intermediates residing within the bilayer. Reason: Specific, structurally and biochemically validated molecular function; central to COQ9's substrate-selection role. Supporting Evidence: PMID:30661980 repurposes the bacterial TetR fold to bind aromatic isoprenes
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput mitochondrial proteome evidence for mitochondrial localization, consistent with the established mitochondrial function of COQ9. Reason: Correct organelle; corroborates other localization annotations.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162186	ACCEPT	Summary: Reactome inner-membrane localization associated with a CoQ-pathway reaction step (COQ3 methylates DeMQ10H2). COQ9 acts on the matrix face of the inner membrane within the CoQ synthome, so the compartment is correct. Reason: Traceable-author localization to the correct compartment.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162187	ACCEPT	Summary: Reactome inner-membrane localization associated with a CoQ-pathway reaction step (COQ6 hydroxylates DHB). Compartment assignment is correct for COQ9. Reason: Traceable-author localization to the correct compartment.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162188	ACCEPT	Summary: Reactome inner-membrane localization associated with a CoQ-pathway reaction step (COQ5 methylates MDMQ10H2). Compartment assignment is correct for COQ9. Reason: Traceable-author localization to the correct compartment.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162193	ACCEPT	Summary: Reactome inner-membrane localization associated with a CoQ-pathway reaction step (COQ3 methylates DHDB). Compartment assignment is correct for COQ9. Reason: Traceable-author localization to the correct compartment.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162194	ACCEPT	Summary: Reactome inner-membrane localization for the reaction step directly involving COQ9 (COQ7:COQ9 octamer hydroxylates DMQ10H2). This is the specific step in which the COQ7:COQ9 module presents DMQ substrate for hydroxylation. Reason: Traceable-author localization to the correct compartment; directly reflects the COQ7:COQ9 hydroxylation module.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162195	ACCEPT	Summary: Reactome inner-membrane localization associated with a CoQ-pathway reaction step (COQ4 decarboxylates MHDB). Compartment assignment is correct for COQ9. Reason: Traceable-author localization to the correct compartment.
GO:0005515 protein binding	IPI PMID:25339443 Mitochondrial COQ9 is a lipid-binding protein that associate...	KEEP AS NON CORE	Summary: IPI protein-binding annotation whose recorded partner is COQ7 (Q99807), established here by co-crystallography/interaction mapping. This is the key functional interaction of COQ9, but the bare "protein binding" term itself is uninformative as a molecular function. Reason: Real and important COQ7 interaction (never removed per policy), retained as non-core because GO:0005515 conveys no specific molecular function; the biology is captured by lipid/isoprenoid binding, complex membership and CoQ biosynthesis. Supporting Evidence: PMID:25339443 COQ9 specifically interacts with COQ7 through a series of conserved residues
GO:0006744 ubiquinone biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity annotation (from mouse ortholog Q8K1Z0) to ubiquinone biosynthetic process, concordant with the experimental annotations to the same term. Reason: Correct core process; redundant with strong experimental evidence.
GO:0008289 lipid binding	IDA PMID:25339443 Mitochondrial COQ9 is a lipid-binding protein that associate...	ACCEPT	Summary: Direct experimental evidence (crystal structure 4RHP with bound di-palmitoyl-phosphatidylethanolamine; mass spectrometry of purified COQ9) that COQ9 is a lipid-binding protein associating with multiple lipid species including CoQ itself. Reason: Defining, experimentally validated molecular function of this non-catalytic lipid-binding protein. Supporting Evidence: PMID:25339443 Our structure also reveals a lipid-binding site
GO:0042803 protein homodimerization activity	IDA PMID:25339443 Mitochondrial COQ9 is a lipid-binding protein that associate...	ACCEPT	Summary: Direct experimental evidence that COQ9 forms a homodimer (an atypical TFR-family dimer). Homodimerization underlies assembly of the higher-order COQ7:COQ9 tetramers and octamers. Reason: Experimentally supported quaternary-structure function relevant to COQ9's assembly into the CoQ module.
GO:0005739 mitochondrion	HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated...	ACCEPT	Summary: High-throughput (phosphoproteomics of muscle mitochondria) detection supporting mitochondrial localization, consistent with the established mitochondrial function of COQ9. Reason: Correct organelle; corroborates other localization annotations.

Gene Description

Existing Annotations Review

Core Functions

Binds membrane phospholipids and lipophilic aromatic-isoprene CoQ-pathway intermediates (including 5-demethoxyubiquinone) within a hydrophobic TetR/FadR-like pocket, as a non-catalytic accessory subunit of the mitochondrial CoQ biosynthetic complex (CoQ synthome).

Selectively binds aromatic-isoprene CoQ intermediates and presents the 5-demethoxyubiquinone substrate directly to the hydroxylase COQ7, thereby activating the penultimate C6-hydroxylation step of coenzyme Q biosynthesis (COQ9 increases COQ7 catalytic efficiency but is itself non-catalytic).

Self-associates into homodimers that, with COQ7, assemble into higher-order membrane-warping COQ7:COQ9 tetramers and octamers of the CoQ biosynthetic module.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

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