COQ7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005743 mitochondrial inner membrane	IBA GO_REF:0000033	ACCEPT	Summary: COQ7 is a peripheral protein of the mitochondrial inner membrane on the matrix side, consistent with its role in the CoQ biosynthetic complex. This is the correct core location and is supported by direct assay (ComplexPortal IDA) and phylogeny across the COQ7 family. Supporting Evidence: file:human/COQ7/COQ7-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0160224 3-demethoxyubiquinone 3-hydroxylase (NADH) activity	IBA GO_REF:0000033	ACCEPT	Summary: This is the core molecular function of COQ7 and matches the enzyme's Rhea reaction. Well supported by phylogeny across the conserved COQ7/CLK-1 family and by direct human biochemistry. Supporting Evidence: PMID:23445365 GB1-hCLK-1 functions as a 5-demethoxyubiquinone-hydroxylase, utilizing its carboxylate-bridged diiron center.
GO:0006744 ubiquinone biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Core biological process. COQ7 performs the penultimate (C6 hydroxylation) step of ubiquinone biosynthesis. Strongly supported across the family and by human/mammalian biochemistry and disease genetics.
GO:2000377 regulation of reactive oxygen species metabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Supported for the moonlighting nuclear pool of COQ7/CLK-1, which regulates a ROS-defensive gene expression program independently of ubiquinone synthesis. This is a genuine but non-core, secondary function distinct from the enzyme's biosynthetic role, so keep it as non-core. Supporting Evidence: PMID:25961505 nuclear CLK-1/COQ7 can potentially regulate metabolic pathways that alter cellular ROS production independently of ubiquinone
GO:0005634 nucleus	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: A distinct uncleaved pool of COQ7/CLK-1 does localize to the nucleus and act there (PMID:25961505), so the phylogenetically-inferred nuclear localization is not wrong. But this is a derived moonlighting function, not the ancestral/core activity of the family (the mitochondrial CoQ hydroxylase); keep the nuclear localization as non-core. Supporting Evidence: PMID:25961505 We have uncovered a distinct nuclear form of CLK-1 that independently regulates lifespan.
GO:0008340 determination of adult lifespan	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: clk-1/COQ7 influences lifespan in C. elegans and heterozygous mice, partly through altered CoQ/ROS metabolism and partly through the nuclear moonlighting pool. This is a real, conserved organismal phenotype but downstream of the core enzymatic function; retain as non-core. Supporting Evidence: PMID:25961505 nuclear CLK-1 can regulate longevity and that this is unrelated to the mitochondrial role of CLK-1 in ubiquinone biosynthesis.
GO:0004497 monooxygenase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Correct but generic parent term. COQ7 is a monooxygenase (it incorporates one oxygen atom into DMQ), but the specific child GO:0160224 (3-demethoxyubiquinone 3-hydroxylase (NADH) activity) captures the actual reaction and is already annotated. Note COQ7 is a carboxylate-bridged di-iron monooxygenase, not a flavin- or heme-dependent one. Over-annotation relative to the specific term. Proposed replacements: 3-demethoxyubiquinone 3-hydroxylase (NADH) activity
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Nuclear localization is experimentally supported for a subpool of COQ7 (PMID:25961505) and is captured by the UniProt Nucleus subcellular location. Genuine but non-core relative to the mitochondrial inner-membrane site of the biosynthetic function.
GO:0005694 chromosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: The nuclear pool of COQ7 associates directly with chromatin (PMID:25961505), consistent with this SubCell-derived Chromosome location. Non-core moonlighting localization. Supporting Evidence: PMID:25961505 the nuclear pool of COQ7 can directly associate with chromatin
GO:0005739 mitochondrion	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Correct but less specific than the mitochondrial inner membrane annotation. Keep as non-core; the informative location is GO:0005743.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: Correct core location, redundant with the experimentally-supported inner membrane annotations. Accept. Supporting Evidence: file:human/COQ7/COQ7-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0006744 ubiquinone biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Correct core biological process, redundant with the experimental IDA/IMP annotations. Accept.
GO:0016709 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen	IEA GO_REF:0000104	MARK AS OVER ANNOTATED	Summary: Accurate parent term describing the class of NAD(P)H-dependent, single-oxygen- incorporating oxygenase reaction that COQ7 performs, but less informative than the specific GO:0160224. Over-annotation relative to the specific activity. Proposed replacements: 3-demethoxyubiquinone 3-hydroxylase (NADH) activity
GO:0031314 extrinsic component of mitochondrial inner membrane	IEA GO_REF:0000104	ACCEPT	Summary: This is a more precise topological description than "mitochondrial inner membrane": COQ7 is a peripheral (extrinsic) membrane protein on the matrix side of the inner membrane. Accurate and informative; accept. Supporting Evidence: file:human/COQ7/COQ7-uniprot.txt Peripheral membrane protein
GO:0160224 3-demethoxyubiquinone 3-hydroxylase (NADH) activity	IEA GO_REF:0000120	ACCEPT	Summary: Core molecular function, redundant with the experimental EXP/IDA annotations and derived here from the Rhea/EC mapping (RHEA:81211, EC:1.14.13.253). Accept.
GO:0005515 protein binding	IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" (IPI to COQ synthome partners identified in the mitochondrial interaction map). The interaction is real but the term is uninformative; the biologically meaningful content (membership in the CoQ biosynthetic complex and the COQ9->COQ7 substrate-presentation interaction) is captured by GO:0110142 and by the core functions. Over-annotated; do not use as a core function. Supporting Evidence: PMID:27499296 we identified a dynamic human CoQ biosynthetic complex involving
GO:0009410 response to xenobiotic stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic ortholog transfer from rat (UniProtKB:Q63619) via Ensembl Compara. There is no direct evidence that human COQ7 functions in a xenobiotic response, and this is not part of its characterized biology. Weak, uninformative electronic transfer; flag as over-annotation rather than a core function.
GO:0005743 mitochondrial inner membrane	IDA PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	ACCEPT	Summary: Direct assignment of COQ7 to the mitochondrial inner membrane by ComplexPortal from the CoQ biosynthetic complex characterization. This is the correct core location. Accept. Supporting Evidence: file:human/COQ7/COQ7-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0006744 ubiquinone biosynthetic process	NAS PMID:28927698 Biochemistry of Mitochondrial Coenzyme Q Biosynthesis.	ACCEPT	Summary: Author statement (review of CoQ biosynthesis) placing COQ7 in ubiquinone biosynthesis. Correct core process. Accept.
GO:0110142 ubiquinone biosynthesis complex	IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	ACCEPT	Summary: COQ7 is a component of the eukaryotic CoQ biosynthetic complex (COQ metabolon / synthome), whose definition explicitly includes COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9. This complex membership is the informative counterpart to the bare "protein binding" annotations. Accept as core complex membership. Supporting Evidence: PMID:38425362 These include COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162186	ACCEPT	Summary: Reactome-derived location for a specific CoQ pathway reaction event. Correct core inner-membrane location (one of several redundant Reactome duplicates). Accept.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162187	ACCEPT	Summary: Redundant Reactome-derived inner-membrane location for another CoQ pathway event. Correct core location. Accept.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162188	ACCEPT	Summary: Redundant Reactome-derived inner-membrane location. Correct core location. Accept.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162193	ACCEPT	Summary: Redundant Reactome-derived inner-membrane location. Correct core location. Accept.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162194	ACCEPT	Summary: Reactome event "COQ7:COQ9 octamer hydroxylates DMQ10H2" — directly describes the COQ7 catalytic step at the inner membrane. Correct core inner-membrane location (one of several redundant Reactome duplicates). Accept.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-2162195	ACCEPT	Summary: Redundant Reactome-derived inner-membrane location. Correct core location. Accept.
GO:0005634 nucleus	EXP PMID:25961505 A nuclear role for the respiratory enzyme CLK-1 in regulatin...	KEEP AS NON CORE	Summary: Experimental evidence (immunostaining, fractionation) that an uncleaved pool of COQ7 localizes to the nucleus. Genuine moonlighting localization; retain as non-core relative to the mitochondrial biosynthetic function. Supporting Evidence: PMID:25961505 endogenous and exogenously expressed COQ7 display both mitochondrial and nuclear immunostaining in HeLa cells
GO:0005694 chromosome	EXP PMID:25961505 A nuclear role for the respiratory enzyme CLK-1 in regulatin...	KEEP AS NON CORE	Summary: Experimentally supported: nuclear COQ7 is enriched in the chromatin fraction and associates directly with chromatin/DNA-protein complexes. Non-core moonlighting localization. Supporting Evidence: PMID:25961505 the uncleaved form of COQ7, but not the R28A mutant, was enriched in the chromatin fraction
GO:0160224 3-demethoxyubiquinone 3-hydroxylase (NADH) activity	EXP PMID:23445365 Aging-associated enzyme human clock-1: substrate-mediated re...	ACCEPT	Summary: Direct biochemical demonstration on purified human CLK-1/COQ7 that it is a 5-demethoxyubiquinone hydroxylase using a carboxylate-bridged diiron center, with substrate-mediated NADH reduction and O2 activation. This is the strongest evidence for the core molecular function. Accept. Supporting Evidence: PMID:23445365 The binding of DMQn (n = 0 or 2) to GB1-hCLK-1 mediates reduction of the diiron center by nicotinamide adenine dinucleotide (NADH) and initiates O2 activation for subsequent DMQ hydroxylation.
GO:0005739 mitochondrion	IDA PMID:25961505 A nuclear role for the respiratory enzyme CLK-1 in regulatin...	KEEP AS NON CORE	Summary: Direct evidence of mitochondrial localization/activity. Correct but less specific than the mitochondrial inner membrane; retain as non-core. Supporting Evidence: PMID:25961505 endogenous and exogenously expressed COQ7 display both mitochondrial and nuclear immunostaining in HeLa cells
GO:0006744 ubiquinone biosynthetic process	IDA PMID:38425362 In vitro construction of the COQ metabolon unveils the molec...	ACCEPT	Summary: In vitro reconstitution of the human/tetrapod COQ metabolon demonstrates COQ7 performing its C6 hydroxylation step within ubiquinone biosynthesis. Direct support for the core biological process. Accept. Supporting Evidence: PMID:38425362 COQ7 is an NADH-dependent hydroxylase that possesses a carboxylate-bridged diiron centre and converts 5 to 6
GO:0160224 3-demethoxyubiquinone 3-hydroxylase (NADH) activity	IDA PMID:38425362 In vitro construction of the COQ metabolon unveils the molec...	ACCEPT	Summary: In vitro reconstitution confirms COQ7 as the NADH-dependent, diiron-dependent hydroxylase catalyzing the C6 step, with COQ9 enhancing its catalytic efficiency. Direct support for the core molecular function. Accept. Supporting Evidence: PMID:38425362 addition of COQ9 increased catalytic efficiency by 1.5-fold, substantiating its role for COQ7 function
GO:0005515 protein binding	IPI PMID:30661980 An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzy...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" IPI to COQ9 (O75208). The meaningful biology is that COQ9 binds and presents the lipophilic DMQ substrate to COQ7; this is captured by complex membership (GO:0110142) and the core functions. Uninformative as a standalone MF; over-annotated. Supporting Evidence: PMID:25339443 COQ9 specifically interacts with COQ7 through a series of conserved residues.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput mitochondrial proteome (MitoCoP) places COQ7 in mitochondria. Correct but less specific than the inner membrane; retain as non-core.
GO:0006744 ubiquinone biosynthetic process	IMP PMID:28409910 Pathogenicity of two COQ7 mutations and responses to 2,4-dih...	ACCEPT	Summary: Patient/mutation study: pathogenic COQ7 variants (V141E, L111P) reduce protein stability and ubiquinone levels, and DHB bypass can restore synthesis in cells lacking COQ7 activity — direct genetic evidence that COQ7 is required for ubiquinone biosynthesis. Core biological process. Accept. Supporting Evidence: PMID:28409910 mutations in the ubiquinone biosynthetic gene COQ7
GO:0005515 protein binding	IPI PMID:25339443 Mitochondrial COQ9 is a lipid-binding protein that associate...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" IPI to COQ9 (O75208) from the study defining the COQ9-COQ7 interaction. Real and important interaction, but "protein binding" is uninformative; the biology (COQ9 presenting substrate to COQ7 within the COQ complex) is captured by GO:0110142 and the core functions. Over-annotated. Supporting Evidence: PMID:25339443 suggesting that COQ9 might serve to present its bound lipid to COQ7.
GO:0005634 nucleus	IDA GO_REF:0000054	KEEP AS NON CORE	Summary: LIFEdb intracellular-localization curation reporting nuclear localization of a COQ7 fusion protein. Consistent with the experimentally-confirmed nuclear pool (PMID:25961505). Non-core moonlighting localization.
GO:0005506 iron ion binding	IDA PMID:23445365 Aging-associated enzyme human clock-1: substrate-mediated re...	NEW	Summary: Proposed new annotation. GOA currently carries only the generic GO:0046872 metal ion binding (IEA from keyword). COQ7 binds a carboxylate-bridged di-iron center (two iron ions per subunit), directly demonstrated for the purified human enzyme, so GO:0005506 iron ion binding is the accurate specific metal-binding MF and should be added. Supporting Evidence: file:human/COQ7/COQ7-uniprot.txt Note=Binds 2 iron ions per subunit. PMID:23445365 GB1-hCLK-1 functions as a 5-demethoxyubiquinone-hydroxylase, utilizing its carboxylate-bridged diiron center.

Gene Description

Existing Annotations Review

Core Functions

COQ7 binds a carboxylate-bridged di-iron center (two iron ions per subunit) via a ferritin-like fold; this diiron cofactor is essential for catalysis and O2 activation and is not replaced by flavin or heme.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

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