NDUFA10

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic (IBA) annotation to the generic cytoplasm. NDUFA10 is a mitochondrial inner-membrane subunit of Complex I; "cytoplasm" is an over-broad localization that does not reflect its actual compartment. Reason: NDUFA10 is imported into mitochondria and integrated into the Complex I membrane arm at the inner membrane; UniProt localizes it to mitochondrion (matrix/inner membrane), so a bare cytoplasm term is a coarse over-annotation. Retained (not removed) as it is an IBA propagation rather than a clearly-wrong IEA. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH GRANULARITY MISMATCH Supporting Evidence: file:human/NDUFA10/NDUFA10-uniprot.txt Mitochondrion matrix
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to the core Complex I process. NDUFA10 participates as a structural accessory subunit of the enzyme that performs NADH-to-ubiquinone electron transport; appropriate as a contributing (non-catalytic) role. Reason: NDUFA10 is a bona fide subunit of Complex I, the enzyme that transfers electrons from NADH to ubiquinone; this process annotation is correct at the complex level. It is a contributing structural role rather than direct catalysis. Supporting Evidence: file:human/NDUFA10/NDUFA10-uniprot.txt Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.
GO:0045271 respiratory chain complex I	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) part_of Complex I. Well supported; NDUFA10 is a genuine structural subunit of the holoenzyme. Reason: Consistent with experimental identification of NDUFA10 as a stable subunit of human Complex I; this is the correct complex-membership term. Supporting Evidence: file:human/NDUFA10/NDUFA10-uniprot.txt Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I)
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: IEA from UniProtKB-SubCell mapping of the "Mitochondrion matrix" location line. NDUFA10 is a membrane-arm subunit; the matrix assignment is a topological inference and is less precise than its inner-membrane localization. Reason: The UniProt subcellular-location line does state mitochondrion matrix, so the IEA mapping is faithful, but the better-supported localization is the mitochondrial inner membrane (Complex I membrane arm); keep as non-core. Supporting Evidence: file:human/NDUFA10/NDUFA10-uniprot.txt Mitochondrion matrix
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO (IEA) mapping from the NDUFA10 InterPro signature to the core Complex I electron-transport process. Consistent with the IBA/experimental complex membership. Reason: The InterPro family (IPR015828 NDUFA10) is specific to this subunit and the process term correctly describes the Complex I reaction it contributes to. Supporting Evidence: file:human/NDUFA10/NDUFA10-uniprot.txt Complex I functions in the transfer of electrons from NADH to the respiratory chain.
GO:1902600 proton transmembrane transport	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: IEA inferred logically from the molecular-function term GO:0008137 (NADH dehydrogenase activity). Proton translocation is a property of the catalytic core (ND subunits) of Complex I, not of the non-catalytic accessory subunit NDUFA10. Reason: This term is auto-inferred from an over-reaching molecular-function assignment. NDUFA10 is explicitly "believed not to be involved in catalysis"; proton pumping is mediated by the membrane-arm core subunits, so attributing proton transmembrane transport to NDUFA10 is an over-annotation. Supporting Evidence: file:human/NDUFA10/NDUFA10-uniprot.txt believed not to be involved in catalysis
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000107	ACCEPT	Summary: IEA transferred from the mouse ortholog (Q99LC3) via Ensembl Compara. Inner-membrane localization is correct for the Complex I membrane arm and is independently supported by human structural/ComplexPortal evidence. Reason: NDUFA10 is part of the hydrophobic (membrane) fraction of Complex I embedded in the inner membrane; the ortholog-based localization is accurate. Supporting Evidence: file:human/NDUFA10/NDUFA10-uniprot.txt component of the hydrophobic protein
GO:0045271 respiratory chain complex I	IEA GO_REF:0000107	ACCEPT	Summary: IEA complex-membership transferred from the mouse ortholog. Correct and redundant with the human experimental part_of annotations. Reason: NDUFA10 is a conserved subunit of Complex I; ortholog-based complex membership is accurate. Supporting Evidence: file:human/NDUFA10/NDUFA10-uniprot.txt Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I)
GO:0005743 mitochondrial inner membrane	IDA PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: Direct-assay (IDA, ComplexPortal) localization to the mitochondrial inner membrane, based on cryo-EM structural placement of NDUFA10 within Complex I in the respiratory megacomplex. This is the best-supported localization. Reason: The megacomplex cryo-EM structure resolves individual human Complex I subunit positions, placing NDUFA10 in the inner-membrane arm; strong experimental support. Supporting Evidence: PMID:28844695 reveals the precise assignment of individual subunits of human CI
GO:0009060 aerobic respiration	NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-...	KEEP AS NON CORE	Summary: NAS (ComplexPortal) high-level process annotation. Complex I is the entry point of the respiratory chain and NDUFA10 contributes structurally; a broad, non-core process term. Reason: Correct at a high level (Complex I function is integral to aerobic respiration/OXPHOS) but generic; NDUFA10's contribution is as a structural subunit, so keep as non-core rather than a core function. Supporting Evidence: PMID:30030361 oxidative phosphorylation system (OXPHOS) complexes
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 (ComplexPortal) annotation linking Complex I to proton-motive-force-driven ATP synthesis. This is downstream of Complex I proton pumping (performed by the core subunits), not a function of the accessory subunit NDUFA10 itself. Reason: ATP synthesis is carried out by Complex V; Complex I contributes the proton gradient via its core subunits. Attributing proton-motive-force ATP synthesis to a non-catalytic accessory subunit is an over-annotation of the whole-pathway role. Supporting Evidence: PMID:27626371 required for the generation of a transmembrane proton gradient used for the synthesis of ATP
GO:0045271 respiratory chain complex I	IPI PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ...	ACCEPT	Summary: IPI (ComplexPortal) complex-membership from physical identification of NDUFA10 within Complex I in the cryo-EM megacomplex structure. Strong support for the core structural role. Reason: NDUFA10 is directly resolved as a subunit of human Complex I in the megacomplex structure; this is a definitive complex-membership annotation. Supporting Evidence: PMID:28844695 reveals the precise assignment of individual subunits of human CI
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput (HTP) mitochondrial-proteome localization. NDUFA10 is a high-confidence mitochondrial protein; correct but a coarse compartment term relative to the inner-membrane localization. Reason: Accurate mitochondrial localization from a high-confidence mitochondrial proteome study, but less specific than the inner-membrane annotation; keep as non-core. Supporting Evidence: PMID:34800366 defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
GO:0045271 respiratory chain complex I	IDA PMID:12611891 The subunit composition of the human NADH dehydrogenase obta...	ACCEPT	Summary: Direct-assay (IDA) complex membership from one-step immunopurification and mass-spectrometric identification of NDUFA10 as one of the human Complex I polypeptides. Core structural annotation. Reason: NDUFA10 was experimentally identified among the resolved human Complex I subunits by immunopurification/MS; a strong, direct complex-membership annotation. Supporting Evidence: PMID:12611891 we can resolve and identify the human homologues of 42 polypeptides detected so far
GO:0045271 respiratory chain complex I	IDA PMID:27626371 Accessory subunits are integral for assembly and function of...	ACCEPT	Summary: Direct-assay (IDA) complex membership from the systematic accessory-subunit knockout/proteomics study, which defines the human Complex I subunit set including NDUFA10. Core structural annotation. Reason: The study experimentally characterizes each accessory subunit of human Complex I and its role in assembly/stability, confirming NDUFA10 as a subunit of the complex. Supporting Evidence: PMID:27626371 the role and necessity of the remaining 31 human accessory subunits
GO:0045271 respiratory chain complex I	NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox...	ACCEPT	Summary: NAS complex membership from the cDNA characterization of nuclear-encoded Complex I subunits (NDUFA10 among the hydrophobic-fraction subunits). Consistent with experimental annotations. Reason: This paper characterizes NDUFA10 as a nuclear-encoded subunit located in the hydrophobic protein fraction of Complex I; complex membership is correct. Supporting Evidence: PMID:9878551 all located within the hydrophobic protein (HP) fraction of complex I
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-163217	ACCEPT	Summary: TAS (Reactome) inner-membrane localization from the Complex I catalytic reaction pathway. Consistent with the membrane-arm localization of NDUFA10. Reason: Reactome places Complex I (and its subunits, including NDUFA10) in the inner mitochondrial membrane where the NADH:ubiquinone oxidoreductase reaction occurs; accurate localization. Supporting Evidence: Reactome:R-HSA-163217 the HP arm lying within the inner mitochondrial membrane
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799178	ACCEPT	Summary: TAS (Reactome) inner-membrane localization from a Complex I biogenesis reaction. Redundant with other inner-membrane annotations; localization is correct. Reason: Correct inner-membrane localization; NDUFA10 is part of the Complex I membrane (hydrophobic) arm embedded in the inner mitochondrial membrane. Corroborates the IDA localization. Supporting Evidence: Reactome:R-HSA-163217 the HP arm lying within the inner mitochondrial membrane
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799179	ACCEPT	Summary: TAS (Reactome) inner-membrane localization from a Complex I biogenesis reaction. Localization correct; redundant with other inner-membrane annotations. Reason: Correct inner-membrane localization; NDUFA10 is part of the Complex I membrane (hydrophobic) arm embedded in the inner mitochondrial membrane. Corroborates the IDA localization. Supporting Evidence: Reactome:R-HSA-163217 the HP arm lying within the inner mitochondrial membrane
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799191	ACCEPT	Summary: TAS (Reactome) inner-membrane localization from a Complex I biogenesis reaction. Localization correct; redundant with other inner-membrane annotations. Reason: Correct inner-membrane localization; NDUFA10 is part of the Complex I membrane (hydrophobic) arm embedded in the inner mitochondrial membrane. Corroborates the IDA localization. Supporting Evidence: Reactome:R-HSA-163217 the HP arm lying within the inner mitochondrial membrane
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799196	ACCEPT	Summary: TAS (Reactome) inner-membrane localization from the final Complex I biogenesis step (assembly factors dissociate to yield mature Complex I). Localization correct. Reason: Correct inner-membrane localization; NDUFA10 is part of the Complex I membrane (hydrophobic) arm embedded in the inner mitochondrial membrane. Corroborates the IDA localization. Supporting Evidence: Reactome:R-HSA-6799196 dissociate from the 980kDa complex to leave mature Complex I
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799197	ACCEPT	Summary: TAS (Reactome) inner-membrane localization from a Complex I biogenesis reaction. Localization correct; redundant with other inner-membrane annotations. Reason: Correct inner-membrane localization; NDUFA10 is part of the Complex I membrane (hydrophobic) arm embedded in the inner mitochondrial membrane. Corroborates the IDA localization. Supporting Evidence: Reactome:R-HSA-163217 the HP arm lying within the inner mitochondrial membrane
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-6799202	ACCEPT	Summary: TAS (Reactome) inner-membrane localization from a Complex I biogenesis reaction. Localization correct; redundant with other inner-membrane annotations. Reason: Correct inner-membrane localization; NDUFA10 is part of the Complex I membrane (hydrophobic) arm embedded in the inner mitochondrial membrane. Corroborates the IDA localization. Supporting Evidence: Reactome:R-HSA-163217 the HP arm lying within the inner mitochondrial membrane
GO:0006120 mitochondrial electron transport, NADH to ubiquinone	NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox...	ACCEPT	Summary: NAS annotation to the core Complex I process from the subunit cDNA characterization paper. NDUFA10 contributes as a structural subunit of the NADH:ubiquinone oxidoreductase. Reason: The paper describes NDUFA10 as a subunit of NADH:ubiquinone oxidoreductase, whose main function is electron transport from NADH to ubiquinone; contributing process role is correct. Supporting Evidence: PMID:9878551 Its main function is the transport of electrons from NADH to ubiquinone
GO:0008137 NADH dehydrogenase (ubiquinone) activity	NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox...	MARK AS OVER ANNOTATED	Summary: NAS molecular-function annotation asserting NDUFA10 enables NADH:ubiquinone oxidoreductase activity. This is the catalytic activity of the whole complex; NDUFA10 is explicitly non-catalytic (an accessory subunit with a degenerate dNK/pseudokinase fold), so an "enables" MF on this subunit over-attributes complex-level catalysis to a structural component. Reason: UniProt states the subunit is "believed not to be involved in catalysis"; catalytic NADH dehydrogenase activity is a property of the assembled complex (core ND/NDUFS/NDUFV subunits). At most NDUFA10 contributes_to this activity. This is not a kinase misannotation, but assigning the holoenzyme MF via enables to an accessory subunit is an over-annotation. Captured instead in core_functions as contributes_to GO:0008137 with molecular_function GO:0005198. Supporting Evidence: file:human/NDUFA10/NDUFA10-uniprot.txt believed not to be involved in catalysis
GO:0005198 structural molecule activity	IDA PMID:27626371 Accessory subunits are integral for assembly and function of...	NEW	Summary: Proposed core molecular function. NDUFA10 is a non-catalytic accessory subunit whose role is structural: it contributes to the integrity, assembly and stability of the Complex I membrane arm. This is the honest MF for the subunit (its dNK/pseudokinase fold is not catalytically active here), in place of the complex-level catalytic GO:0008137 enables annotation. Reason: Captures the structural (rather than catalytic) role of this accessory subunit; knockout studies show accessory subunits are strictly required for assembly and stability of Complex I. Supporting Evidence: PMID:27626371 25 subunits are strictly required for assembly of a functional complex
GO:0032981 mitochondrial respiratory chain complex I assembly	IMP PMID:27626371 Accessory subunits are integral for assembly and function of...	NEW	Summary: Proposed core biological process. Loss of NDUFA10 (and other accessory subunits) disrupts assembly and stability of Complex I; patient fibroblasts with NDUFA10 mutations show disturbed complex I assembly, supporting an assembly role. Reason: Systematic accessory-subunit knockouts and disease data implicate NDUFA10 in Complex I assembly/stability, a process not explicitly captured in existing GOA. Supporting Evidence: PMID:27626371 25 subunits are strictly required for assembly of a functional complex

Gene Description

Existing Annotations Review

Core Functions

Structural subunit that contributes to the integrity, assembly and stability of the membrane arm of mitochondrial respiratory Complex I; adopts a deoxyribonucleoside-kinase-like fold but is catalytically inactive (a pseudoenzyme) in this role.

As a subunit of the NADH:ubiquinone oxidoreductase holoenzyme, contributes to the complex-level catalytic activity that transfers electrons from NADH to ubiquinone; NDUFA10 itself does not carry out the redox chemistry.

Required for the assembly and function of Complex I; participates in mitochondrial electron transport from NADH to ubiquinone as an integral structural subunit, and its loss disrupts complex assembly and stability.

References

📚 Additional Documentation

Notes

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