MT-ND5

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0001666 response to hypoxia	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: IEA (Ensembl Compara) annotation to response to hypoxia, projected from rat Mt-nd5. Reason: A physiological response projected from a rat expression study. ND5 is a structural core subunit of Complex I and there is no evidence that it does any of the work of sensing or responding to hypoxia or hydrogen peroxide; changes in its expression are an indirect effect. Supporting Evidence: file:human/MT-ND5/MT-ND5-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain 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:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: HTP annotation to mitochondrion. Reason: Correct; ND5 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-ND5/MT-ND5-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: ND5 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-ND5/MT-ND5-uniprot.txt Mitochondrion inner membrane file:human/MT-ND5/MT-ND5-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: ND5 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-ND5/MT-ND5-uniprot.txt Mitochondrion inner membrane file:human/MT-ND5/MT-ND5-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: ND5 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-ND5/MT-ND5-uniprot.txt Mitochondrion inner membrane file:human/MT-ND5/MT-ND5-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: ND5 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-ND5/MT-ND5-uniprot.txt Mitochondrion inner membrane file:human/MT-ND5/MT-ND5-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-5419271	ACCEPT	Summary: TAS annotation to mitochondrial inner membrane (Reactome:R-HSA-5419271). Reason: ND5 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-ND5/MT-ND5-uniprot.txt Mitochondrion inner membrane file:human/MT-ND5/MT-ND5-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: ND5 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-ND5/MT-ND5-uniprot.txt Mitochondrion inner membrane file:human/MT-ND5/MT-ND5-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: ND5 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-ND5/MT-ND5-uniprot.txt Mitochondrion inner membrane file:human/MT-ND5/MT-ND5-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: ND5 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-ND5/MT-ND5-uniprot.txt Mitochondrion inner membrane file:human/MT-ND5/MT-ND5-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	IMP PMID:15250827 Structural organization of mitochondrial human complex I: ro...	ACCEPT	Summary: IMP annotation to mitochondrial electron transport, NADH to ubiquinone. Reason: This is the process carried out by Complex I, and ND5 is a core subunit required for it; loss or pathogenic variants of ND5 reduce NADH:ubiquinone oxidoreductase activity. Core process. Supporting Evidence: file:human/MT-ND5/MT-ND5-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain 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:0006120 mitochondrial electron transport, NADH to ubiquinone	NAS PMID:3921850 Six unidentified reading frames of human mitochondrial DNA e...	ACCEPT	Summary: NAS annotation to mitochondrial electron transport, NADH to ubiquinone. Reason: This is the process carried out by Complex I, and ND5 is a core subunit required for it; loss or pathogenic variants of ND5 reduce NADH:ubiquinone oxidoreductase activity. Core process. Supporting Evidence: file:human/MT-ND5/MT-ND5-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.
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. ND5 is the distal antiporter-like subunit of the membrane arm and carries the terminal proton-translocation unit, 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-ND5/MT-ND5-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:15250827 Structural organization of mitochondrial human complex I: ro...	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. ND5 is the distal antiporter-like subunit of the membrane arm and carries the terminal proton-translocation unit, 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-ND5/MT-ND5-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	NAS PMID:3921850 Six unidentified reading frames of human mitochondrial DNA e...	MODIFY	Summary: NAS 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. ND5 is the distal antiporter-like subunit of the membrane arm and carries the terminal proton-translocation unit, 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-ND5/MT-ND5-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. PMID:3921850 We conclude that the six reading frames encode components of the respiratory-chain NADH dehydrogenase.
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-ND5/MT-ND5-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:0015990 electron transport coupled proton transport	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation to electron transport coupled proton transport. Reason: The membrane arm of Complex I is the proton pump, and ND5 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 The rest of MA is formed by three homologous antiporter-like subunits (ALS), ND2/NuoN, ND4/NuoM and ND5/NuoL, containing 14 conserved transmembrane helices (TM) each. PMID:36920092 eventually resulting in proton expulsion from the distal antiporter-like subunit 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:0032981 mitochondrial respiratory chain complex I assembly	IMP PMID:15250827 Structural organization of mitochondrial human complex I: ro...	KEEP AS NON CORE	Summary: IMP annotation to mitochondrial respiratory chain complex I assembly. Reason: Loss or pathogenic variants of ND5 block or destabilise Complex I assembly, and ND5 enters at a defined assembly step. This shows ND5 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:15250827 However, in cells lacking ND4 or ND5, very low amounts of 24 kDa subunit were found associated with the membranes Reactome:R-HSA-6799197 Distal components of the membrane arm MT-ND4 and 5 associate with the 550kDa complex to form the 815kDa complex
GO:0042542 response to hydrogen peroxide	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: IEA (Ensembl Compara) annotation to response to hydrogen peroxide, projected from rat Mt-nd5. Reason: A physiological response projected from a rat expression study. ND5 is a structural core subunit of Complex I and there is no evidence that it does any of the work of sensing or responding to hypoxia or hydrogen peroxide; changes in its expression are an indirect effect. Supporting Evidence: file:human/MT-ND5/MT-ND5-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain 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:0042773 ATP synthesis coupled electron transport	IEA GO_REF:0000002	MODIFY	Summary: IEA (InterPro) annotation to ATP synthesis coupled electron transport. Reason: Correct but generic; the specific process for a mitochondrial Complex I subunit is mitochondrial electron transport, NADH to ubiquinone, which is also annotated. Proposed replacements: mitochondrial electron transport, NADH to ubiquinone Supporting Evidence: file:human/MT-ND5/MT-ND5-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain 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: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	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation placing MT-ND5 in respiratory chain complex I. Reason: ND5 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-ND5/MT-ND5-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	IDA PMID:12611891 The subunit composition of the human NADH dehydrogenase obta...	ACCEPT	Summary: IDA annotation placing MT-ND5 in respiratory chain complex I. Reason: ND5 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-ND5/MT-ND5-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	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation placing MT-ND5 in respiratory chain complex I. Reason: ND5 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-ND5/MT-ND5-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-ND5 in respiratory chain complex I. Reason: ND5 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-ND5/MT-ND5-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	NAS PMID:3921850 Six unidentified reading frames of human mitochondrial DNA e...	ACCEPT	Summary: NAS annotation placing MT-ND5 in respiratory chain complex I. Reason: ND5 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-ND5/MT-ND5-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:0015078 proton transmembrane transporter activity	ISS PMID:36920092 From the 'black box' to 'domino effect' mechanism: what have...	NEW	Summary: Proposed new annotation: ND5 enables proton transmembrane transporter activity as the distal antiporter-like proton-translocation unit of Complex I. Reason: ND5 is one of three antiporter-like (Mrp-family) subunits of the Complex I membrane arm. Each carries a proton-uptake and a proton-exit half-channel, and current mechanisms place final proton expulsion in the distal antiporter-like subunit. Translocating protons is the subunit-level activity by which ND5 contributes to the complex's proton-pumping NADH:ubiquinone oxidoreductase activity. The evidence comes from structures of the conserved mammalian and bacterial enzyme, so ISS. Supporting Evidence: PMID:36920092 The rest of MA is formed by three homologous antiporter-like subunits (ALS), ND2/NuoN, ND4/NuoM and ND5/NuoL, containing 14 conserved transmembrane helices (TM) each. PMID:36920092 eventually resulting in proton expulsion from the distal antiporter-like subunit PMID:32747785 The four units each comprise a proton-uptake and a proton-exit half-channel

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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