NDUFB9 (also called Complex I-B22, CI-B22, or LYR motif-containing protein 3) is a nuclear-encoded accessory ("supernumerary") subunit of mitochondrial respiratory chain Complex I (NADH:ubiquinone oxidoreductase), the first and largest enzyme of the oxidative phosphorylation electron transport chain. Complex I couples electron transfer from NADH to ubiquinone with translocation of protons across the inner mitochondrial membrane. NDUFB9 is one of ~45 subunits of the mammalian holoenzyme and belongs to the LYR protein family. It is a component of the membrane arm of the complex, a peripheral inner-membrane protein whose bulk faces the matrix side, and it is non-catalytic: it does not itself carry out electron transfer or proton pumping. Its role is structural, contributing to the assembly and stability of the mature complex; loss of the subunit destabilizes the complex and causes isolated Complex I deficiency (mitochondrial complex I deficiency, nuclear type 24; MC1DN24). NDUFB9 is incorporated into higher-order respiratory supercomplexes (respirasomes) together with Complexes III and IV.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0045271 respiratory chain complex I | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically-inferred (IBA) membership in respiratory chain complex I. This is correct and represents the core cellular location/complex membership of NDUFB9. Strongly corroborated by multiple direct experimental (IDA/IPI) annotations to the same term. Supporting Evidence: file:human/NDUFB9/NDUFB9-uniprot.txt Mammalian complex I is composed of 45 different subunits. |
| GO:0005739 mitochondrion | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO electronic mapping to mitochondrion. Correct but very general; the more specific and experimentally supported location is the mitochondrial inner membrane / respiratory chain complex I. Kept as a broad, non-core localization. Supporting Evidence: file:human/NDUFB9/NDUFB9-uniprot.txt Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation to mitochondrial inner membrane. Correct: UniProt records NDUFB9 as a peripheral inner-membrane protein on the matrix side, and this is the location of the membrane arm of Complex I. Consistent with the IDA annotation to the same term from ComplexPortal. Supporting Evidence: file:human/NDUFB9/NDUFB9-uniprot.txt Mitochondrion inner membrane |
| GO:0006120 mitochondrial electron transport, NADH to ubiquinone | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic annotation to the core Complex I biological process. NDUFB9 is non-catalytic, but as an integral structural subunit it contributes to the assembled complex that performs NADH-to-ubiquinone electron transport, so involved_in is appropriate at the process level. This is a core biological process for the gene. Supporting Evidence: file:human/NDUFB9/NDUFB9-uniprot.txt involved in catalysis. Complex I functions in the transfer of electrons |
| GO:1902600 proton transmembrane transport | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Automatically inferred (GO_REF:0000108, from the NADH dehydrogenase MF GO:0008137) proton transmembrane transport. Complex I does translocate protons, but this term is derived from a molecular-function assignment (GO:0008137) that NDUFB9 does not itself carry out; the subunit is non-catalytic. The specific, experimentally supported process for this gene is mitochondrial electron transport, NADH to ubiquinone (GO:0006120); the generic proton-transport term is an over-annotation for an accessory subunit. Supporting Evidence: file:human/NDUFB9/NDUFB9-uniprot.txt involved in catalysis. Complex I functions in the transfer of electrons |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MARK AS OVER ANNOTATED | Summary: IPI "protein binding" from a proteome-scale interaction screen. The evidence supports a physical interaction but the bare GO:0005515 term is uninformative about NDUFB9's molecular function. Retained (per policy, IPI protein binding is not removed) but flagged as over-annotated; the biologically meaningful molecular role is captured as structural molecule activity in core_functions. |
| GO:0005515 protein binding | IPI PMID:17500595 Huntingtin interacting proteins are genetic modifiers of neu... | MARK AS OVER ANNOTATED | Summary: IPI "protein binding" from a huntingtin-interactome AP-MS/Y2H screen (NDUFB9 recovered as an HTT-fragment interactor). Physical association is supported, but the term is uninformative and the interaction is not part of NDUFB9's core function. Retained but marked over-annotated. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: IPI "protein binding" from a proteome-scale (HI-II-14) human interactome map. Uninformative bare binding term; retained per policy but flagged as over-annotated. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: IPI "protein binding" from a large-scale interactome (BioPlex-type) dataset. Physical interaction supported but term uninformative; retained, flagged as over-annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: IPI "protein binding" from the HuRI reference binary interactome. Bare binding term; retained per policy, flagged as over-annotated. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: IPI "protein binding" from a neurodegenerative-disease interactome mapping study. Uninformative bare binding term; retained, flagged as over-annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: IPI "protein binding" from the BioPlex 3.0 dual proteome-scale interactome. Bare binding term; retained per policy, flagged as over-annotated. |
| GO:0045271 respiratory chain complex I | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-Compara ortholog-transfer (IEA) of complex membership from mouse Ndufb9. Correct and consistent with the direct experimental annotations to the same term; a redundant but valid statement of the core complex membership. Supporting Evidence: file:human/NDUFB9/NDUFB9-uniprot.txt Mammalian complex I is composed of 45 different subunits. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ... | ACCEPT | Summary: Direct assignment (ComplexPortal, IDA) of NDUFB9 to the mitochondrial inner membrane, based on the cryo-EM megacomplex structure that places each Complex I subunit. This is the correct, experimentally grounded subcellular location and is core. Supporting Evidence: PMID:28844695 precise assignment of individual subunits of |
| GO:0009060 aerobic respiration | NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-... | KEEP AS NON CORE | Summary: NAS (ComplexPortal) annotation to aerobic respiration. True at the pathway level — Complex I is part of the OXPHOS/respiratory chain — but this is a broad process inherited from complex membership rather than a specific function of NDUFB9. Kept as a non-core process; the specific core process is mitochondrial electron transport, NADH to ubiquinone. Supporting Evidence: PMID:30030361 complexes I, III and IV interact with each other |
| 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 to proton-motive-force-driven ATP synthesis. This describes the downstream OXPHOS outcome of the proton gradient; NDUFB9 is a non-catalytic accessory subunit of Complex I and does not itself synthesize ATP or pump protons. This is an over-annotation for an accessory subunit — the proton gradient is generated by the complex, and ATP synthesis is performed by Complex V. Supporting Evidence: PMID:30030361 supernumerary' subunits that play essential roles in assembly, regulation |
| GO:0045271 respiratory chain complex I | IPI PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ... | ACCEPT | Summary: IPI (ComplexPortal) complex membership from the cryo-EM megacomplex structure showing NDUFB9 as a component of Complex I. Correct and core; corroborates the other part_of GO:0045271 annotations. Supporting Evidence: PMID:28844695 precise assignment of individual subunits of |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: IDA (HPA immunofluorescence) localization to mitochondrion. Correct but general; the specific location is the inner membrane. Retained as a broad, non-core localization. Supporting Evidence: file:human/NDUFB9/NDUFB9-uniprot.txt Mitochondrion inner membrane |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | KEEP AS NON CORE | Summary: High-throughput (HTP) proteomic assignment to mitochondrion. Consistent with the well-established mitochondrial localization of NDUFB9; general and non-core relative to the specific inner-membrane/Complex I location. Supporting Evidence: file:human/NDUFB9/NDUFB9-uniprot.txt Mitochondrion inner membrane |
| GO:0045271 respiratory chain complex I | IDA PMID:12611891 The subunit composition of the human NADH dehydrogenase obta... | ACCEPT | Summary: Direct experimental (IDA) demonstration of NDUFB9 as a component of human Complex I by one-step immunopurification and mass spectrometry. This is a strong, core annotation establishing complex membership. Supporting Evidence: PMID:12611891 we can resolve and identify the human PMID:12611891 isolating this multisubunit |
| GO:0045271 respiratory chain complex I | IDA PMID:27626371 Accessory subunits are integral for assembly and function of... | ACCEPT | Summary: Direct experimental (IDA) complex membership from the Stroud et al. systematic knockout/complexome study, which identified NDUFB9 among the accessory subunits of human Complex I and showed accessory subunits are integral to assembly and stability. Core annotation. Supporting Evidence: PMID:27626371 required for assembly of a functional complex and 1 subunit is essential for |
| 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 historical cDNA-characterization paper of human Complex I subunits. Correct; redundant with the stronger IDA/IPI annotations to the same term. Core complex membership. Supporting Evidence: PMID:9878551 the transport of electrons from NADH to ubiquinone, which is |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-163217 | ACCEPT | Summary: TAS (Reactome) inner-membrane localization, from the reaction in which Complex I oxidises NADH and reduces CoQ. Correct location; consistent with experimental IDA annotations. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799178 | ACCEPT | Summary: TAS (Reactome) inner-membrane localization, from a Complex I biogenesis reaction. Correct location; consistent with the experimental annotations. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799179 | ACCEPT | Summary: TAS (Reactome) inner-membrane localization, from a Complex I biogenesis reaction. Correct and consistent with experimental annotations. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799191 | ACCEPT | Summary: TAS (Reactome) inner-membrane localization, from a Complex I biogenesis reaction. Correct and consistent with experimental annotations. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799196 | ACCEPT | Summary: TAS (Reactome) inner-membrane localization, from a Complex I biogenesis reaction. Correct and consistent with experimental annotations. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799197 | ACCEPT | Summary: TAS (Reactome) inner-membrane localization, from a Complex I biogenesis reaction. Correct and consistent with experimental annotations. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799202 | ACCEPT | Summary: TAS (Reactome) inner-membrane localization, from a Complex I biogenesis reaction. Correct and consistent with experimental annotations. |
| 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 (mitochondrial electron transport, NADH to ubiquinone). NDUFB9 is an integral structural subunit of the complex that performs this process; involved_in is appropriate. Core biological process. Supporting Evidence: PMID:9878551 the transport of electrons from NADH to ubiquinone, which is |
| 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 "enables" NADH dehydrogenase (ubiquinone) activity. NDUFB9 is a non-catalytic accessory subunit and does NOT independently enable this catalytic activity — the activity is a property of the assembled complex and its core catalytic subunits. Rather than enables, NDUFB9 contributes_to this complex-level activity as a structural subunit (see core_functions). The direct "enables" assignment is an over-annotation. Supporting Evidence: file:human/NDUFB9/NDUFB9-uniprot.txt involved in catalysis. Complex I functions in the transfer of electrons |
| GO:0005743 mitochondrial inner membrane | TAS PMID:8661098 The human B22 subunit of the NADH-ubiquinone oxidoreductase ... | ACCEPT | Summary: TAS inner-membrane localization from the 1996 paper identifying the human B22 subunit as a mitochondrial respiratory-chain protein. Correct location; consistent with all other localization evidence. Supporting Evidence: PMID:8661098 a mitochondrial protein in the respiratory electron transport chain |
| GO:0006120 mitochondrial electron transport, NADH to ubiquinone | TAS PMID:8661098 The human B22 subunit of the NADH-ubiquinone oxidoreductase ... | ACCEPT | Summary: TAS annotation to the core Complex I process. Appropriate for NDUFB9 as an integral subunit of the NADH:ubiquinone oxidoreductase complex. Core biological process; redundant with the NAS/IEA annotations to the same term. Supporting Evidence: PMID:8661098 a mitochondrial protein in the respiratory electron transport chain |
| GO:0007605 sensory perception of sound | TAS PMID:8661098 The human B22 subunit of the NADH-ubiquinone oxidoreductase ... | MARK AS OVER ANNOTATED | Summary: TAS annotation to sensory perception of sound, derived from the 1996 paper's observation that NDUFB9/B22 maps to a chromosome-8q13 region implicated in branchio-oto-renal syndrome and its speculation that the gene is a candidate for hearing loss. This is a positional-candidacy / disease-association inference, not a demonstrated molecular or cellular role of NDUFB9 in auditory perception, and it is not supported by subsequent functional work. It is an over-annotation of the gene's actual function (a structural subunit of Complex I); any hearing phenotype would be a systemic consequence of Complex I deficiency rather than a specific auditory function. Supporting Evidence: PMID:8661098 this gene should be considered a strong candidate for involvement in |
| GO:0008137 NADH dehydrogenase (ubiquinone) activity | TAS PMID:8661098 The human B22 subunit of the NADH-ubiquinone oxidoreductase ... | MARK AS OVER ANNOTATED | Summary: TAS "enables" NADH dehydrogenase (ubiquinone) activity. As with the NAS assignment of this term, NDUFB9 is a non-catalytic accessory subunit that does not independently enable this catalytic activity; it contributes_to the complex-level activity as a structural component. Over-annotation at the subunit level. Supporting Evidence: file:human/NDUFB9/NDUFB9-uniprot.txt involved in catalysis. Complex I functions in the transfer of electrons |
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Download this section (compressed HTML)Q: Does NDUFB9 have any regulatory role (e.g. in Complex I turnover, oxidative stress response, or supercomplex/respirasome formation) beyond its structural scaffolding contribution to the membrane arm?
Q: Is the LYR motif of NDUFB9 involved in Fe-S/acyl-carrier (LYRM-family) type interactions during assembly, or is it purely structural in the mature complex?
Experiment: Quantitative complexome profiling (BN-PAGE / mass spectrometry) of NDUFB9 knockout versus wild-type cells to define which Complex I subassembly intermediates accumulate and which neighbouring membrane-arm subunits are destabilized.
Experiment: Structure-guided functional analysis of the MC1DN24 variant (p.Leu64Pro) by cryo-EM and complex-stability assays to determine whether it perturbs assembly of the membrane arm or destabilizes the fully assembled holoenzyme.
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