MT-ND6

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: HTP annotation to mitochondrion. Reason: Correct; ND6 is encoded and translated inside mitochondria and resides in the inner membrane. The term is less specific than mitochondrial inner membrane, which is also annotated, but it is not wrong. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane PMID:34800366 defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation to mitochondrion. Reason: Correct; ND6 is encoded and translated inside mitochondria and resides in the inner membrane. The term is less specific than mitochondrial inner membrane, which is also annotated, but it is not wrong. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane PMID:34800366 defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
GO:0005743 mitochondrial inner membrane	IDA PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: IDA annotation to mitochondrial inner membrane (PMID:28844695). Reason: ND6 is a multi-pass integral membrane subunit of the Complex I membrane arm, which is embedded in the inner mitochondrial membrane. Correct and appropriately specific location. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane file:human/MT-ND6/MT-ND6-uniprot.txt Multi-pass membrane protein PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation to mitochondrial inner membrane (GO_REF:0000120). Reason: ND6 is a multi-pass integral membrane subunit of the Complex I membrane arm, which is embedded in the inner mitochondrial membrane. Correct and appropriately specific location. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane file:human/MT-ND6/MT-ND6-uniprot.txt Multi-pass membrane protein PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII
GO:0005743 mitochondrial inner membrane	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation to mitochondrial inner membrane (GO_REF:0000024). Reason: ND6 is a multi-pass integral membrane subunit of the Complex I membrane arm, which is embedded in the inner mitochondrial membrane. Correct and appropriately specific location. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane file:human/MT-ND6/MT-ND6-uniprot.txt Multi-pass membrane protein PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-163217	ACCEPT	Summary: TAS annotation to mitochondrial inner membrane (Reactome:R-HSA-163217). Reason: ND6 is a multi-pass integral membrane subunit of the Complex I membrane arm, which is embedded in the inner mitochondrial membrane. Correct and appropriately specific location. The Reactome reference is a mitochondrial translation or Complex I assembly/catalysis event, and the stated compartment is correct for it. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane file:human/MT-ND6/MT-ND6-uniprot.txt Multi-pass membrane protein PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII Reactome:R-HSA-163217 This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799179	ACCEPT	Summary: TAS annotation to mitochondrial inner membrane (Reactome:R-HSA-6799179). Reason: ND6 is a multi-pass integral membrane subunit of the Complex I membrane arm, which is embedded in the inner mitochondrial membrane. Correct and appropriately specific location. The Reactome reference is a mitochondrial translation or Complex I assembly/catalysis event, and the stated compartment is correct for it. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane file:human/MT-ND6/MT-ND6-uniprot.txt Multi-pass membrane protein PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII Reactome:R-HSA-163217 This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799196	ACCEPT	Summary: TAS annotation to mitochondrial inner membrane (Reactome:R-HSA-6799196). Reason: ND6 is a multi-pass integral membrane subunit of the Complex I membrane arm, which is embedded in the inner mitochondrial membrane. Correct and appropriately specific location. The Reactome reference is a mitochondrial translation or Complex I assembly/catalysis event, and the stated compartment is correct for it. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane file:human/MT-ND6/MT-ND6-uniprot.txt Multi-pass membrane protein PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII Reactome:R-HSA-163217 This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799197	ACCEPT	Summary: TAS annotation to mitochondrial inner membrane (Reactome:R-HSA-6799197). Reason: ND6 is a multi-pass integral membrane subunit of the Complex I membrane arm, which is embedded in the inner mitochondrial membrane. Correct and appropriately specific location. The Reactome reference is a mitochondrial translation or Complex I assembly/catalysis event, and the stated compartment is correct for it. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane file:human/MT-ND6/MT-ND6-uniprot.txt Multi-pass membrane protein PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII Reactome:R-HSA-163217 This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799199	ACCEPT	Summary: TAS annotation to mitochondrial inner membrane (Reactome:R-HSA-6799199). Reason: ND6 is a multi-pass integral membrane subunit of the Complex I membrane arm, which is embedded in the inner mitochondrial membrane. Correct and appropriately specific location. The Reactome reference is a mitochondrial translation or Complex I assembly/catalysis event, and the stated compartment is correct for it. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane file:human/MT-ND6/MT-ND6-uniprot.txt Multi-pass membrane protein PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII Reactome:R-HSA-163217 This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799202	ACCEPT	Summary: TAS annotation to mitochondrial inner membrane (Reactome:R-HSA-6799202). Reason: ND6 is a multi-pass integral membrane subunit of the Complex I membrane arm, which is embedded in the inner mitochondrial membrane. Correct and appropriately specific location. The Reactome reference is a mitochondrial translation or Complex I assembly/catalysis event, and the stated compartment is correct for it. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane file:human/MT-ND6/MT-ND6-uniprot.txt Multi-pass membrane protein PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII Reactome:R-HSA-163217 This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9937394	ACCEPT	Summary: TAS annotation to mitochondrial inner membrane (Reactome:R-HSA-9937394). Reason: ND6 is a multi-pass integral membrane subunit of the Complex I membrane arm, which is embedded in the inner mitochondrial membrane. Correct and appropriately specific location. The Reactome reference is a mitochondrial translation or Complex I assembly/catalysis event, and the stated compartment is correct for it. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Mitochondrion inner membrane file:human/MT-ND6/MT-ND6-uniprot.txt Multi-pass membrane protein PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII Reactome:R-HSA-163217 This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space.
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation to mitochondrial electron transport, NADH to ubiquinone. Reason: This is the process carried out by Complex I, and ND6 is a core subunit required for it; loss or pathogenic variants of ND6 reduce NADH:ubiquinone oxidoreductase activity. Core process. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain PMID:14595656 Cybrid clones showed a specific complex I defect that correlates with the mutant heteroplasmy levels. PMID:8644732 Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	IMP PMID:14595656 Impaired complex I assembly in a Leigh syndrome patient with...	ACCEPT	Summary: IMP annotation to mitochondrial electron transport, NADH to ubiquinone. Reason: This is the process carried out by Complex I, and ND6 is a core subunit required for it; loss or pathogenic variants of ND6 reduce NADH:ubiquinone oxidoreductase activity. Core process. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain PMID:14595656 Cybrid clones showed a specific complex I defect that correlates with the mutant heteroplasmy levels. PMID:8644732 Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	IMP PMID:8644732 Genetic and biochemical impairment of mitochondrial complex ...	ACCEPT	Summary: IMP annotation to mitochondrial electron transport, NADH to ubiquinone. Reason: This is the process carried out by Complex I, and ND6 is a core subunit required for it; loss or pathogenic variants of ND6 reduce NADH:ubiquinone oxidoreductase activity. Core process. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain PMID:14595656 Cybrid clones showed a specific complex I defect that correlates with the mutant heteroplasmy levels. PMID:8644732 Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency
GO:0008137 NADH dehydrogenase (ubiquinone) activity	IEA GO_REF:0000120	MODIFY	Summary: IEA annotation with the enables qualifier to NADH dehydrogenase (ubiquinone) activity, the EC 7.1.1.2 activity of the whole complex (NADH + Q + 5H+ in = NAD+ + QH2 + 4H+ out). Reason: The activity belongs to the assembled holoenzyme: NADH oxidation, the flavin and Fe-S cofactors and the terminal electron donor N2 are all in nuclear-encoded peripheral-arm subunits. ND6 is one of the small membrane-arm subunits that, with ND1, ND3 and ND4L, forms the E-channel proton-translocation unit, and its TMH3 controls the active/deactive transition, so it is required for, and contributes to, the complex activity but does not carry it alone. The term is right; the qualifier should be contributes_to. Its own subunit-level activity is captured in core_functions. Proposed replacements: NADH dehydrogenase (ubiquinone) activity Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Essential for the catalytic activity and assembly of complex I PMID:15250827 Mitochondria-encoded ND (NADH dehydrogenase) subunits, as components of the hydrophobic part of complex I, are essential for NADH:ubiquinone oxidoreductase activity.
GO:0008137 NADH dehydrogenase (ubiquinone) activity	IMP PMID:14595656 Impaired complex I assembly in a Leigh syndrome patient with...	MODIFY	Summary: IMP annotation with the enables qualifier to NADH dehydrogenase (ubiquinone) activity, the EC 7.1.1.2 activity of the whole complex (NADH + Q + 5H+ in = NAD+ + QH2 + 4H+ out). Reason: The activity belongs to the assembled holoenzyme: NADH oxidation, the flavin and Fe-S cofactors and the terminal electron donor N2 are all in nuclear-encoded peripheral-arm subunits. ND6 is one of the small membrane-arm subunits that, with ND1, ND3 and ND4L, forms the E-channel proton-translocation unit, and its TMH3 controls the active/deactive transition, so it is required for, and contributes to, the complex activity but does not carry it alone. The term is right; the qualifier should be contributes_to. Its own subunit-level activity is captured in core_functions. Proposed replacements: NADH dehydrogenase (ubiquinone) activity Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Essential for the catalytic activity and assembly of complex I PMID:14595656 Cybrid clones showed a specific complex I defect that correlates with the mutant heteroplasmy levels. PMID:8644732 Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency
GO:0008137 NADH dehydrogenase (ubiquinone) activity	IMP PMID:8644732 Genetic and biochemical impairment of mitochondrial complex ...	MODIFY	Summary: IMP annotation with the enables qualifier to NADH dehydrogenase (ubiquinone) activity, the EC 7.1.1.2 activity of the whole complex (NADH + Q + 5H+ in = NAD+ + QH2 + 4H+ out). Reason: The activity belongs to the assembled holoenzyme: NADH oxidation, the flavin and Fe-S cofactors and the terminal electron donor N2 are all in nuclear-encoded peripheral-arm subunits. ND6 is one of the small membrane-arm subunits that, with ND1, ND3 and ND4L, forms the E-channel proton-translocation unit, and its TMH3 controls the active/deactive transition, so it is required for, and contributes to, the complex activity but does not carry it alone. The term is right; the qualifier should be contributes_to. Its own subunit-level activity is captured in core_functions. Proposed replacements: NADH dehydrogenase (ubiquinone) activity Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Essential for the catalytic activity and assembly of complex I PMID:14595656 Cybrid clones showed a specific complex I defect that correlates with the mutant heteroplasmy levels. PMID:8644732 Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency
GO:0009060 aerobic respiration	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	KEEP AS NON CORE	Summary: NAS annotation to aerobic respiration. Reason: Correct but very general; Complex I is the entry point of the respiratory chain. The specific process mitochondrial electron transport, NADH to ubiquinone is the core process. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain PMID:30030361 it is now well established that complexes I, III and IV interact with each other, forming the so-called respiratory supercomplexes
GO:0032981 mitochondrial respiratory chain complex I assembly	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: IEA annotation to mitochondrial respiratory chain complex I assembly. Reason: Loss or pathogenic variants of ND6 block or destabilise Complex I assembly, and ND6 enters at a defined assembly step. This shows ND6 is a required building block of the complex rather than an assembly factor; the annotation is kept, but the core role is catalytic (contribution to proton-pumping NADH:ubiquinone oxidoreduction). Supporting Evidence: PMID:14595656 suggesting that the mutation has a profound effect on complex I assembly and/or stability Reactome:R-HSA-6799199 Membrane arm subunits COA1:MT-ND2, TMEM186:MT-ND3, MT-ND6 and NDUFB6 associate with the assembly factors
GO:0032981 mitochondrial respiratory chain complex I assembly	IMP PMID:14595656 Impaired complex I assembly in a Leigh syndrome patient with...	KEEP AS NON CORE	Summary: IMP annotation to mitochondrial respiratory chain complex I assembly. Reason: Loss or pathogenic variants of ND6 block or destabilise Complex I assembly, and ND6 enters at a defined assembly step. This shows ND6 is a required building block of the complex rather than an assembly factor; the annotation is kept, but the core role is catalytic (contribution to proton-pumping NADH:ubiquinone oxidoreduction). Supporting Evidence: PMID:14595656 suggesting that the mutation has a profound effect on complex I assembly and/or stability Reactome:R-HSA-6799199 Membrane arm subunits COA1:MT-ND2, TMEM186:MT-ND3, MT-ND6 and NDUFB6 associate with the assembly factors
GO:0042776 proton motive force-driven mitochondrial ATP synthesis	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	MARK AS OVER ANNOTATED	Summary: NAS annotation (ComplexPortal) to proton motive force-driven mitochondrial ATP synthesis. Reason: Complex I generates the proton motive force but does not synthesise ATP; that process is carried out by ATP synthase. The annotation reflects a whole-OXPHOS view of the complex and over-states this subunit's role. Supporting Evidence: Reactome:R-HSA-163217 This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space.
GO:0045271 respiratory chain complex I	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation placing MT-ND6 in respiratory chain complex I. Reason: ND6 is one of the seven mtDNA-encoded core subunits of the membrane arm of Complex I; membership is supported by immunopurification of human Complex I, the human megacomplex structure, and the original identification of the ND reading frames as Complex I components. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain PMID:3921850 We conclude that the six reading frames encode components of the respiratory-chain NADH dehydrogenase. PMID:12611891 we can resolve and identify the human homologues of 42 polypeptides detected so far in the more extensively studied beef heart complex I PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII
GO:0045271 respiratory chain complex I	IPI PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: IPI annotation placing MT-ND6 in respiratory chain complex I. Reason: ND6 is one of the seven mtDNA-encoded core subunits of the membrane arm of Complex I; membership is supported by immunopurification of human Complex I, the human megacomplex structure, and the original identification of the ND reading frames as Complex I components. Supporting Evidence: file:human/MT-ND6/MT-ND6-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain PMID:3921850 We conclude that the six reading frames encode components of the respiratory-chain NADH dehydrogenase. PMID:12611891 we can resolve and identify the human homologues of 42 polypeptides detected so far in the more extensively studied beef heart complex I PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII
GO:1902600 proton transmembrane transport	IEA GO_REF:0000108	ACCEPT	Summary: IEA annotation to proton transmembrane transport. Reason: The membrane arm of Complex I is the proton pump, and ND6 forms part of one of its four proton-translocation units. Proton transport coupled to electron transfer is core work done by this subunit, not a downstream consequence. Supporting Evidence: PMID:36920092 which form, together with part of ND1, the E-channel containing key glutamates PMID:32747785 The four units each comprise a proton-uptake and a proton-exit half-channel Reactome:R-HSA-163217 This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space.
GO:0015078 proton transmembrane transporter activity	ISS PMID:36920092 From the 'black box' to 'domino effect' mechanism: what have...	NEW	Summary: Proposed new annotation: ND6 contributes to proton transmembrane transporter activity as part of the E-channel proton-translocation unit of Complex I. Reason: ND6 is one of the small membrane-arm subunits (ND3, ND6, ND4L, with part of ND1) that form the E-channel, the proton-translocation unit nearest the quinone site, and its TMH3 conformation gates the proton path in the open/deactive state. The activity is carried out jointly with ND1, ND3 and ND4L and depends on the assembled complex. Evidence is from conserved mammalian structures, so ISS. Supporting Evidence: PMID:36920092 which form, together with part of ND1, the E-channel containing key glutamates PMID:32747785 The four units each comprise a proton-uptake and a proton-exit half-channel PMID:32972993 In the induced deactive state, the open conformation is arrested by the ND6 subunit.

Gene Description

Existing Annotations Review

Core Functions

References

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