NDUFB7 (also known as Complex I-B18, CI-B18, and the NADH-ubiquinone oxidoreductase B18 subunit) 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 system. It is a non-catalytic structural subunit: electron transfer from NADH to ubiquinone, coupled to proton translocation across the inner membrane, is performed by the conserved core subunits (which bind FMN and iron-sulfur clusters), while NDUFB7 and the other accessory subunits contribute to assembly, stability, and structural integrity of the holoenzyme. NDUFB7 is a twin CX9C protein containing two C-X9-C motifs that fold into a helix-coil-helix (CHCH) domain stabilized by two intramolecular disulfide bonds; it is imported and oxidatively folded via the MIA40/CHCHD4 disulfide-relay pathway of the mitochondrial intermembrane space. The mature protein is a peripheral inner-membrane protein located at the intermembrane-space surface of the membrane (proximal) arm of Complex I, where it (together with NDUFA8) is thought to help stabilize the membrane domain. It also carries an N-terminal N-myristoyl glycine lipid modification. Biallelic loss-of-function variants in NDUFB7 cause autosomal-recessive mitochondrial complex I deficiency nuclear type 39 (MC1DN39), with reduced Complex I assembly and activity, presenting as congenital lactic acidosis and hypertrophic cardiomyopathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0045271 respiratory chain complex I | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred (IBA) membership of NDUFB7 in respiratory chain complex I. This is correct and directly supported by experimental structural and mass-spectrometry data (below): NDUFB7/B18 is a bona fide stable subunit of the Complex I holoenzyme. This is the core cellular-component location and is captured in core_functions as in_complex. Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Accessory subunit of the mitochondrial membrane respiratory |
| GO:0005739 mitochondrion | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO electronic annotation to the parent organelle term "mitochondrion". True but non-specific: the more precise mitochondrial inner membrane / intermembrane space localizations (supported experimentally) are the informative locations. Retained as a correct but general parent. Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (IEA) inner-membrane localization, consistent with experimental data. NDUFB7 is a peripheral inner-membrane protein (part of the Complex I membrane arm). Accurate and captured in core_functions locations. Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion inner membrane |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic (UniProt SubCell) intermembrane-space annotation, matching the experimental IDA localization of NDUFB7 to the IMS surface of Complex I. NDUFB7 faces the intermembrane space from the inner membrane and is imported via the MIA40 relay. Accurate; captured in core_functions locations. Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion intermembrane space |
| GO:1902600 proton transmembrane transport | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Electronic term inferred logically from the Complex I catalytic activity GO:0008137. Complex I couples NADH:ubiquinone oxidoreduction to proton translocation, but that transport is driven by the conserved core membrane subunits, not by the non-catalytic accessory subunit NDUFB7. Not a direct function of this subunit; the proton-motive process is better captured at the complex level. Marking as over-annotated for the individual subunit. Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt that is believed not to be |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: High-throughput binary (Y2H) interactome IPI annotation to the generic term "protein binding". The reported partners (e.g. MEIS2, GYS1, CCNC, transcription factors and zinc-finger proteins) are not Complex I subunits and largely reflect non-physiological or promiscuous binary interactions rather than NDUFB7's biological role. The bare "protein binding" term is uninformative about the actual molecular function (structural subunit of Complex I). Retained per policy (not removed) but flagged as over-annotated / uninformative. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Binary interactome (Y2H) IPI annotation to the generic "protein binding" from a neurodegenerative-disease interactome screen (partner SPRED1). Not a Complex I subunit and not informative about NDUFB7's structural function. Retained per policy but flagged as over-annotated / uninformative. Supporting Evidence: PMID:32814053 systematic yeast two-hybrid |
| GO:0045271 respiratory chain complex I | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic (Ensembl Compara ortholog transfer) membership in respiratory chain complex I. Correct and redundant with the experimental IDA/IPI/IBA complex-membership annotations. Retained as a supporting (non-core-duplicating) annotation. Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Accessory subunit of the mitochondrial membrane respiratory |
| GO:0005743 mitochondrial inner membrane | IDA PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ... | ACCEPT | Summary: IDA inner-membrane localization from the cryo-EM structure of the human respiratory megacomplex I2III2IV2, which resolves NDUFB7 as a subunit of the Complex I membrane arm. Accurate; captured in core_functions locations. 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 annotation (ComplexPortal) to aerobic respiration, a valid high-level biological process for a Complex I subunit. Complex I is the entry point of the respiratory chain / oxidative phosphorylation system. Kept as a correct but general (non-core) process; the more specific process for this subunit is mitochondrial electron transport, NADH to ubiquinone. Supporting Evidence: PMID:30030361 assembly of the five 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 annotation (ComplexPortal) to proton-motive-force-driven ATP synthesis. This is the terminal OXPHOS process (Complex V); Complex I contributes to the proton-motive force upstream, but ATP synthesis itself is not a direct process of Complex I or of the non-catalytic subunit NDUFB7. Over-annotation of the individual subunit. Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt that is believed not to be |
| GO:0045271 respiratory chain complex I | IPI PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ... | ACCEPT | Summary: IPI complex-membership annotation (ComplexPortal) from the human megacomplex cryo-EM structure. Directly establishes NDUFB7 as a physical subunit of Complex I. Core cellular-component; captured in core_functions as in_complex. Supporting Evidence: PMID:28844695 precise assignment of individual subunits of |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | KEEP AS NON CORE | Summary: High-throughput (HTP) mitochondrial-proteome localization to the parent "mitochondrion" term. True but non-specific; the informative locations are the inner membrane and intermembrane space. Retained as a correct general parent. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome |
| GO:0045271 respiratory chain complex I | IDA PMID:12611891 The subunit composition of the human NADH dehydrogenase obta... | ACCEPT | Summary: IDA complex-membership from the one-step immunopurification and mass-spectrometry identification of human Complex I subunits, which identified NDUFB7/B18 as a component. Strong direct evidence for physical membership. Core cellular-component; captured in core_functions as in_complex. Supporting Evidence: PMID:12611891 subunit composition of the human NADH dehydrogenase |
| GO:0045271 respiratory chain complex I | IDA PMID:27626371 Accessory subunits are integral for assembly and function of... | ACCEPT | Summary: IDA complex-membership from the systematic accessory-subunit knockout / quantitative-proteomics study, which analyzed NDUFB7 among the human Complex I accessory subunits. Confirms NDUFB7 as an integral member of the holoenzyme. Core cellular-component; captured in core_functions as in_complex. Supporting Evidence: PMID:27626371 Accessory subunits are integral for assembly and function of human mitochondrial |
| GO:0005743 mitochondrial inner membrane | EXP PMID:21310150 NDUFB7 and NDUFA8 are located at the intermembrane surface o... | ACCEPT | Summary: Experimental (EXP) inner-membrane localization from the study establishing that NDUFB7 (and NDUFA8) sit at the intermembrane-space surface of Complex I within the inner membrane. NDUFB7 is a peripheral inner-membrane protein. Accurate; captured in core_functions locations. Supporting Evidence: PMID:21310150 NDUFB7 and NDUFA8 are located at the intermembrane surface of complex I |
| GO:0008137 NADH dehydrogenase (ubiquinone) activity | IMP PMID:33502047 Severe congenital lactic acidosis and hypertrophic cardiomyo... | MARK AS OVER ANNOTATED | Summary: IMP annotation directly assigning the catalytic MF "NADH dehydrogenase (ubiquinone) activity" to NDUFB7, based on the patient study in which a biallelic intronic variant reduced NDUFB7 protein and reduced Complex I activity, with complementation restoring function. The evidence establishes that NDUFB7 is REQUIRED for holoenzyme catalytic activity, but the catalytic activity itself is carried out by the conserved core (FMN/Fe-S) subunits, not by the non-catalytic accessory subunit NDUFB7 (UniProt: "believed not to be involved in catalysis"). Assigning the complex-level catalytic MF directly (enables) to a structural subunit is an over-annotation; the honest relationship is captured in core_functions via contributes_to_molecular_function (GO:0008137), with the subunit's own MF being structural molecule activity (GO:0005198). Retained per policy (experimental annotation not removed) and marked as over-annotated. Supporting Evidence: PMID:33502047 reduction of the NDUFB7 protein and reduced complex I activity file:human/NDUFB7/NDUFB7-uniprot.txt that is believed not to be |
| GO:0005739 mitochondrion | HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated... | KEEP AS NON CORE | Summary: HDA (high-throughput direct assay) mitochondrial localization from a phosphoproteomics study of isolated human muscle mitochondria. Consistent with the parent organelle location; the specific inner-membrane / IMS locations are more informative. Retained as a correct general parent. Supporting Evidence: PMID:20833797 phosphorylation of inner membrane protein complexes |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-163217 | KEEP AS NON CORE | Summary: TAS inner-membrane localization asserted by Reactome (Complex I redox reaction). Correct and redundant with the experimental inner-membrane annotations. Retained as supporting (non-core-duplicating). Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799178 | KEEP AS NON CORE | Summary: TAS inner-membrane localization from a Reactome Complex I biogenesis reaction. Correct and redundant with the experimental inner-membrane annotations. Retained as supporting (non-core-duplicating). Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799179 | KEEP AS NON CORE | Summary: TAS inner-membrane localization from a Reactome Complex I biogenesis reaction. Correct and redundant with the experimental inner-membrane annotations. Retained as supporting (non-core-duplicating). Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799191 | KEEP AS NON CORE | Summary: TAS inner-membrane localization from a Reactome Complex I biogenesis reaction. Correct and redundant with the experimental inner-membrane annotations. Retained as supporting (non-core-duplicating). Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799196 | KEEP AS NON CORE | Summary: TAS inner-membrane localization from a Reactome Complex I biogenesis reaction. Correct and redundant with the experimental inner-membrane annotations. Retained as supporting (non-core-duplicating). Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799197 | KEEP AS NON CORE | Summary: TAS inner-membrane localization from a Reactome Complex I biogenesis reaction. Correct and redundant with the experimental inner-membrane annotations. Retained as supporting (non-core-duplicating). Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-6799202 | KEEP AS NON CORE | Summary: TAS inner-membrane localization from a Reactome Complex I biogenesis reaction. Correct and redundant with the experimental inner-membrane annotations. Retained as supporting (non-core-duplicating). Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion inner membrane |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:21310150 NDUFB7 and NDUFA8 are located at the intermembrane surface o... | ACCEPT | Summary: IDA intermembrane-space localization from the study demonstrating NDUFB7 (and NDUFA8) at the IMS surface of Complex I. This is the most informative single-subunit localization for NDUFB7 (it faces the IMS from the inner membrane) and is consistent with its twin-CX9C, MIA40-relay import. Accurate; captured in core_functions locations. Supporting Evidence: PMID:21310150 NDUFB7 and NDUFA8 are located at the intermembrane surface of complex I file:human/NDUFB7/NDUFB7-uniprot.txt Mitochondrion intermembrane space |
| GO:0006120 mitochondrial electron transport, NADH to ubiquinone | NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox... | ACCEPT | Summary: NAS involvement in mitochondrial electron transport, NADH to ubiquinone. This is the appropriate pathway-level biological process for a Complex I subunit: NDUFB7 is required for the holoenzyme that performs this process, though it is not itself catalytic. Retained as a core biological process. Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt Complex I functions in the transfer of electrons |
| 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 annotation assigning NDUFB7 as directly enabling the catalytic MF "NADH dehydrogenase (ubiquinone) activity". That activity is carried out by the conserved FMN/Fe-S-bearing core subunits of Complex I; UniProt explicitly states NDUFB7 is an accessory subunit believed not to be involved in catalysis. Assigning the catalytic MF directly (enables) to a non-catalytic accessory subunit is an over-annotation; the honest relationship is captured in core_functions via contributes_to_molecular_function (GO:0008137), with the subunit's own MF being structural molecule activity (GO:0005198). Supporting Evidence: file:human/NDUFB7/NDUFB7-uniprot.txt that is believed not to be |
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