NDUFS8 (TYKY subunit; Complex I-23kDa) is a nuclear-encoded core catalytic subunit of mitochondrial respiratory Complex I (NADH:ubiquinone oxidoreductase, EC 7.1.1.2). It is a component of the iron-sulfur (IP) peripheral arm of the complex and coordinates two [4Fe-4S] clusters (N6a and N6b) through two ferredoxin-type domains; these clusters form part of the intramolecular electron-transfer wire that carries electrons from NADH toward ubiquinone. NDUFS8 is essential both for Complex I catalytic activity and for its assembly/stability. The protein is imported into mitochondria (cleavable transit peptide) and resides in the mitochondrial inner membrane as a peripheral membrane protein on the matrix side. It is highly conserved from bacteria (NuoI) to humans and is ubiquitously expressed, with highest levels in heart and skeletal muscle. Recessive loss-of-function mutations cause mitochondrial complex I deficiency (MC1DN2) and Leigh syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003954 NADH dehydrogenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation that NDUFS8 contributes to NADH dehydrogenase activity as part of Complex I. NADH oxidation is a property of the assembled complex; the contributes_to qualifier correctly reflects that no single subunit catalyzes the reaction alone. Reason: Consistent with NDUFS8 being a core subunit of the NADH:ubiquinone oxidoreductase; the contributes_to qualifier is appropriate for a whole-complex activity. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor |
| GO:0006120 mitochondrial electron transport, NADH to ubiquinone | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation to the core Complex I biological process, electron transport from NADH to ubiquinone. This is the central function of the complex to which NDUFS8 contributes as an Fe-S-carrying core subunit. Reason: Directly represents NDUFS8's role in the NADH-to-ubiquinone electron transfer chain; strongly supported across orthologs and by literature. Supporting Evidence: PMID:9878551 Its main function is the transport of electrons from NADH to ubiquinone, which is accompanied by translocation of protons from the mitochondrial matrix to the intermembrane space. |
| GO:0045271 respiratory chain complex I | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation placing NDUFS8 as part of respiratory chain complex I. This is the correct cellular-component/complex assignment. Reason: NDUFS8 is a well-established core subunit of Complex I in all organisms examined; complex membership is confirmed structurally and biochemically. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation to mitochondrial inner membrane, the correct anatomical location of NDUFS8 as a peripheral inner-membrane subunit of Complex I on the matrix side. Reason: Matches UniProt subcellular location (inner membrane, peripheral, matrix side) and the location of the assembled complex; supported by an independent IDA annotation (PMID:28844695). Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0008137 NADH dehydrogenase (ubiquinone) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (RHEA:29091 / EC:7.1.1.2) to the Complex I catalytic activity, matching the UniProt CATALYTIC ACTIVITY and EC assignment. This is the core molecular function of the complex to which NDUFS8 belongs. Reason: The RHEA/EC-based reaction is exactly the Complex I reaction; NDUFS8 is a core subunit carrying Fe-S clusters of the electron-transfer wire. Supported by IMP (PMID:22499348) showing NDUFS8 variants impair enzyme activity. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based electronic annotation to the generic term membrane. This is correct but far less informative than the specific mitochondrial inner membrane localization already annotated. Reason: Too general; NDUFS8 localizes specifically to the mitochondrial inner membrane, which is already annotated (GO:0005743). Replace the generic term with the specific one. Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0016651 oxidoreductase activity, acting on NAD(P)H | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based electronic annotation to a parent oxidoreductase term. It is not wrong but is a generalization of the specific Complex I activity. Reason: The specific activity, NADH dehydrogenase (ubiquinone) activity (GO:0008137), is already annotated and better represents the function; generalize/replace with the specific child term. Proposed replacements: NADH dehydrogenase (ubiquinone) activity Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 |
| GO:0051539 4 iron, 4 sulfur cluster binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic annotation to [4Fe-4S] cluster binding. NDUFS8 contains two 4Fe-4S ferredoxin-type domains and binds two [4Fe-4S] clusters that form part of the electron-transfer wire of Complex I. This is a genuine core molecular function of the subunit. Reason: Strongly supported - UniProt annotates two 4Fe-4S ferredoxin-type domains and eight cysteine ligands coordinating two [4Fe-4S] clusters; historically the TYKY ferredoxin patterns were thought to bind cluster N-2 (PMID:9837812). Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Note=Binds 2 [4Fe-4S] cluster. PMID:9837812 contains two 4Fe4S ferredoxin consensus patterns, which have long been thought to provide the binding site for the iron-sulfur cluster N-2 |
| GO:1902600 proton transmembrane transport | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Electronic annotation inferred logically from the Complex I catalytic activity (GO:0008137). While Complex I as a whole is a proton pump, the proton translocation is performed by the membrane-arm ND subunits, not by the IP-fragment TYKY subunit that carries the Fe-S clusters. Reason: NDUFS8 is a peripheral-arm iron-sulfur subunit; proton pumping is a property of the membrane arm (ND2/ND4/ND5, NDUFB/NDUFA modules). Assigning proton-transmembrane-transport directly to this subunit over-attributes a whole-complex/membrane-arm activity to a non-transporting electron-carrier subunit. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt This is a component of the iron-sulfur (IP) fragment of the enzyme |
| GO:0045271 respiratory chain complex I | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (ARBA/ortholog-based) annotation of Complex I membership, redundant with the well-supported experimental and phylogenetic annotations to the same term. Reason: Correct complex membership; consistent with experimental IDA/IMP/IPI annotations to GO:0045271. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits |
| GO:0005743 mitochondrial inner membrane | IDA PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ... | ACCEPT | Summary: ComplexPortal IDA localizing NDUFS8 to the mitochondrial inner membrane, based on the cryo-EM structure of the human respiratory megacomplex I2III2IV2 in which individual Complex I subunits were assigned. Reason: Direct structural assignment of Complex I subunits in the inner membrane; matches UniProt subcellular location. Supporting Evidence: PMID:28844695 The structure not only reveals the precise assignment of individual subunits of human CI and CIII |
| GO:0009060 aerobic respiration | NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-... | KEEP AS NON CORE | Summary: ComplexPortal NAS annotation placing Complex I (and thus NDUFS8) in aerobic respiration. This is a correct but high-level pathway process describing the role of the whole OXPHOS system rather than NDUFS8's direct molecular activity. Reason: True at the pathway level but broader than the core electron-transport function; retain as a non-core process annotation. Supporting Evidence: PMID:30030361 core proteins, performing the catalytic activities |
| GO:0042776 proton motive force-driven mitochondrial ATP synthesis | NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-... | MARK AS OVER ANNOTATED | Summary: ComplexPortal NAS annotation linking Complex I to proton-motive-force-driven ATP synthesis. Complex I contributes to the proton-motive force, but ATP synthesis is carried out by Complex V; for NDUFS8 this is a downstream pathway-level role. Reason: This annotation conflates Complex I's contribution to the proton motive force with ATP synthesis, which is carried out by Complex V (ATP synthase). NDUFS8's role is upstream (electron transport and proton pumping); it does not itself synthesize ATP, so proton motive force-driven ATP synthesis is an over-annotation. Supporting Evidence: PMID:30030361 assembly of the five oxidative phosphorylation system (OXPHOS) complexes |
| GO:0045271 respiratory chain complex I | IPI PMID:28844695 Architecture of Human Mitochondrial Respiratory Megacomplex ... | ACCEPT | Summary: ComplexPortal IPI (physical-interaction-based) annotation of Complex I membership from the cryo-EM megacomplex structure. Reason: Correct complex membership, supported by the structural study; redundant with other GO:0045271 annotations. Supporting Evidence: PMID:28844695 precise assignment of individual subunits of human CI and CIII |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput proteomic evidence (high-confidence human mitochondrial proteome) placing NDUFS8 in the mitochondrion. Correct but coarse relative to the inner-membrane localization. Reason: Accurate organelle-level localization; consistent with the more specific inner-membrane annotations. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome |
| GO:0045271 respiratory chain complex I | IMP PMID:11112787 Human complex I defects can be resolved by monoclonal antibo... | ACCEPT | Summary: IMP annotation of Complex I membership from a study resolving human Complex I assembly defects by monoclonal antibodies, including an NDUFS8 patient. Reason: Experimental support for NDUFS8 being a subunit of Complex I whose defect alters the complex; defer to curator who read the full text. Supporting Evidence: PMID:11112787 the other patients had defects in NDUFV1, NDUFS2 (two patients), NDUFS4 (two patients), NDUFS7, and NDUFS8 |
| GO:0045271 respiratory chain complex I | IDA PMID:12611891 The subunit composition of the human NADH dehydrogenase obta... | ACCEPT | Summary: IDA annotation of Complex I membership from one-step immunopurification and mass-spectrometric identification of the human NADH dehydrogenase subunit composition. Reason: Direct biochemical demonstration that NDUFS8 co-purifies as a subunit of human Complex I. Supporting Evidence: 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 |
| GO:0045271 respiratory chain complex I | IDA PMID:31536960 Rewiring of the Human Mitochondrial Interactome during Neuro... | ACCEPT | Summary: IDA annotation of Complex I / respirasome membership from a mitochondrial co-fractionation and interactome study of human cells. Reason: Supports NDUFS8 as part of the respirasome/Complex I; consistent with all other complex-membership evidence. Supporting Evidence: PMID:31536960 Regulators of the Respirasome and Neurogenesis |
| GO:0045271 respiratory chain complex I | NAS PMID:9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone ox... | ACCEPT | Summary: NAS annotation of Complex I membership from the cDNA characterization of human Complex I subunits. Reason: Consistent with NDUFS8 being one of the characterized human Complex I subunits; redundant with stronger experimental evidence. Supporting Evidence: PMID:9878551 Now all currently known 41 proteins of human NADH:ubiquinone oxidoreductase have been characterized |
| GO:0006120 mitochondrial electron transport, NADH to ubiquinone | IMP PMID:22499348 Molecular diagnosis in mitochondrial complex I deficiency us... | ACCEPT | Summary: IMP annotation of the core electron-transport process, based on NDUFS8 patient variants that decrease Complex I enzyme activity, with WT cDNA rescue of complex I activity confirming pathogenicity. Reason: Strong experimental support that NDUFS8 is required for NADH-to-ubiquinone electron transport (Complex I activity); a core function. Supporting Evidence: PMID:22499348 Expression of wild-type cDNA in mutant cell lines rescued complex I activity and assembly, thus providing a functional validation of their pathogenicity. |
| GO:0008137 NADH dehydrogenase (ubiquinone) activity | IMP PMID:22499348 Molecular diagnosis in mitochondrial complex I deficiency us... | ACCEPT | Summary: IMP annotation to the Complex I catalytic activity based on NDUFS8 variants that reduce enzyme activity, rescued by WT cDNA. This underpins the UniProt EC 7.1.1.2 / CATALYTIC ACTIVITY assignment for NDUFS8. Reason: Experimentally supported core molecular function; NDUFS8 is required for the NADH:ubiquinone oxidoreductase activity of Complex I. Supporting Evidence: PMID:22499348 rescued complex I activity and assembly, thus providing a functional validation of their pathogenicity |
| GO:0032981 mitochondrial respiratory chain complex I assembly | IMP PMID:22499348 Molecular diagnosis in mitochondrial complex I deficiency us... | ACCEPT | Summary: IMP annotation to Complex I assembly, based on NDUFS8 variants that impair complex I assembly, rescued by WT cDNA. UniProt notes NDUFS8 is essential for both catalytic activity and assembly of Complex I. Reason: Experimentally supported role in Complex I assembly; a core function of this subunit. Supporting Evidence: PMID:22499348 rescued complex I activity and assembly file:human/NDUFS8/NDUFS8-uniprot.txt Essential for the catalytic activity and assembly of complex I |
| GO:0005515 protein binding | IPI PMID:31536960 Rewiring of the Human Mitochondrial Interactome during Neuro... | MARK AS OVER ANNOTATED | Summary: IPI annotation recording a physical interaction of NDUFS8 with RAB5IF (UniProtKB:Q9BUV8) detected in a mitochondrial interactome/co-fractionation study. Bare protein binding is uninformative about molecular function. Reason: Per curation policy, the generic protein binding term does not convey a specific molecular function. The interaction is real but the term is uninformative; retain but flag as over-annotated rather than remove the experimental IPI. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Interacts with RAB5IF (PubMed:31536960) |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-163217 | MARK AS OVER ANNOTATED | Summary: Reactome TAS annotation to mitochondrial matrix. NDUFS8 is an inner-membrane peripheral subunit facing the matrix; the matrix assignment is a coarse localization that is less precise than the annotated inner-membrane location. Reason: UniProt places NDUFS8 as an inner-membrane peripheral protein on the matrix side, not a soluble matrix protein. The more informative and accurate inner-membrane term (GO:0005743) is already annotated; the matrix term over-generalizes the location. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Peripheral membrane protein |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6788523 | MARK AS OVER ANNOTATED | Summary: Reactome TAS annotation to mitochondrial matrix (from a Complex I biogenesis reaction). Coarse localization for an inner-membrane peripheral subunit. Reason: Same rationale as the other Reactome matrix annotations; the inner-membrane location (GO:0005743) is more accurate and already annotated. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Peripheral membrane protein |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6799178 | MARK AS OVER ANNOTATED | Summary: Reactome TAS annotation to mitochondrial matrix (Complex I assembly intermediate reaction). Coarse localization for an inner-membrane peripheral subunit. Reason: The inner-membrane location (GO:0005743) is more accurate and already annotated; matrix over-generalizes. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Peripheral membrane protein |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6799179 | MARK AS OVER ANNOTATED | Summary: Reactome TAS annotation to mitochondrial matrix (Complex I assembly reaction). Coarse localization for an inner-membrane peripheral subunit. Reason: The inner-membrane location (GO:0005743) is more accurate and already annotated; matrix over-generalizes. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Peripheral membrane protein |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6799191 | MARK AS OVER ANNOTATED | Summary: Reactome TAS annotation to mitochondrial matrix (Complex I assembly reaction). Coarse localization for an inner-membrane peripheral subunit. Reason: The inner-membrane location (GO:0005743) is more accurate and already annotated; matrix over-generalizes. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Peripheral membrane protein |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6799196 | MARK AS OVER ANNOTATED | Summary: Reactome TAS annotation to mitochondrial matrix (Complex I assembly reaction). Coarse localization for an inner-membrane peripheral subunit. Reason: The inner-membrane location (GO:0005743) is more accurate and already annotated; matrix over-generalizes. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Peripheral membrane protein |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6799197 | MARK AS OVER ANNOTATED | Summary: Reactome TAS annotation to mitochondrial matrix (Complex I assembly reaction). Coarse localization for an inner-membrane peripheral subunit. Reason: The inner-membrane location (GO:0005743) is more accurate and already annotated; matrix over-generalizes. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Peripheral membrane protein |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6799202 | MARK AS OVER ANNOTATED | Summary: Reactome TAS annotation to mitochondrial matrix (Complex I assembly reaction). Coarse localization for an inner-membrane peripheral subunit. Reason: The inner-membrane location (GO:0005743) is more accurate and already annotated; matrix over-generalizes. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Peripheral membrane protein |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6799203 | MARK AS OVER ANNOTATED | Summary: Reactome TAS annotation to mitochondrial matrix (Complex I assembly reaction). Coarse localization for an inner-membrane peripheral subunit. Reason: The inner-membrane location (GO:0005743) is more accurate and already annotated; matrix over-generalizes. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Peripheral membrane protein |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6800868 | MARK AS OVER ANNOTATED | Summary: Reactome TAS annotation to mitochondrial matrix (IP subcomplex formation reaction). Coarse localization for an inner-membrane peripheral subunit. Reason: The inner-membrane location (GO:0005743) is more accurate and already annotated; matrix over-generalizes. Supporting Evidence: file:human/NDUFS8/NDUFS8-uniprot.txt Peripheral membrane protein |
| GO:0032981 mitochondrial respiratory chain complex I assembly | IMP PMID:11112787 Human complex I defects can be resolved by monoclonal antibo... | ACCEPT | Summary: IMP annotation to Complex I assembly from a study distinguishing catalytic versus assembly defects among Complex I patients, including an NDUFS8 case, using monoclonal antibodies and sucrose-gradient analysis. Reason: Experimental support that NDUFS8 defects affect Complex I assembly; consistent with the established role of this subunit in assembly/stability. Supporting Evidence: PMID:11112787 helps distinguish catalytic versus assembly defects and further distinguishes between mutations in different subunits |
| GO:0032981 mitochondrial respiratory chain complex I assembly | IMP PMID:15159508 Late-onset Leigh syndrome in a patient with mitochondrial co... | ACCEPT | Summary: IMP annotation to Complex I assembly from a late-onset Leigh syndrome case with NDUFS8 mutations; Western blot showed reduced NDUFS8 and other Complex I subunits, indicating NDUFS8 is essential for assembly/stability of the complex. Reason: Direct patient-based evidence that NDUFS8 is required for Complex I assembly or stability; a core function. Supporting Evidence: PMID:15159508 this subunit is essential for either the assembly or stability of complex I |
| GO:0003954 NADH dehydrogenase activity | IMP PMID:14749350 Differences in assembly or stability of complex I and other ... | ACCEPT | Summary: IMP annotation (contributes_to) to NADH dehydrogenase activity from a BN-PAGE study of Complex I assembly/stability in complex I-deficient patients. Reason: Consistent with NDUFS8 contributing to the whole-complex NADH dehydrogenase activity; the contributes_to qualifier is appropriate. Supporting Evidence: PMID:14749350 an important decrease in the levels of intact complex I in patients harboring mutations in nuclear-encoded complex I subunits |
| GO:0003954 NADH dehydrogenase activity | IMP PMID:15159508 Late-onset Leigh syndrome in a patient with mitochondrial co... | ACCEPT | Summary: IMP annotation (contributes_to) to NADH dehydrogenase activity from the NDUFS8 late-onset Leigh syndrome case with partial Complex I defect. Reason: NDUFS8 contributes to the whole-complex NADH dehydrogenase activity, which is reduced in this patient; contributes_to qualifier is appropriate. Supporting Evidence: PMID:15159508 one patient with late-onset disease and partial complex I defect |
| GO:0005739 mitochondrion | IDA PMID:9666055 Genomic structure of the human NDUFS8 gene coding for the ir... | ACCEPT | Summary: IDA annotation localizing the TYKY (NDUFS8) subunit to mitochondria, based on immunodetection in placental mitochondria. Correct organelle-level localization. Reason: Direct immunodetection of the mature TYKY subunit in mitochondria; consistent with the more specific inner-membrane annotations. Supporting Evidence: PMID:9666055 Immunodetection of the TYKY subunit in placental mitochondria after two-dimensional gel electrophoresis |
| GO:0006120 mitochondrial electron transport, NADH to ubiquinone | NAS PMID:9666055 Genomic structure of the human NDUFS8 gene coding for the ir... | ACCEPT | Summary: NAS annotation of the core Complex I electron-transport process, based on characterization of the NDUFS8/TYKY subunit of the mitochondrial NADH:ubiquinone oxidoreductase. Reason: Correct core process; redundant with the stronger IMP/IBA annotations to GO:0006120. Supporting Evidence: PMID:9666055 TYKY subunit of the human mitochondrial NADH:ubiquinone oxidoreductase (Complex I) |
| GO:0008137 NADH dehydrogenase (ubiquinone) activity | IMP PMID:9837812 The first nuclear-encoded complex I mutation in a patient wi... | ACCEPT | Summary: IMP annotation (contributes_to) to the Complex I catalytic activity from the first report of a nuclear-encoded Complex I (NDUFS8) mutation causing Leigh syndrome with isolated complex I deficiency. Reason: NDUFS8 contributes to the NADH:ubiquinone oxidoreductase activity, which is deficient in these patients; contributes_to is appropriate for a whole-complex activity. Supporting Evidence: PMID:9837812 two compound heterozygous transitions in a patient with neuropathologically proven Leigh syndrome |
| 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 electron-transport process, based on the statement that the main function of complex I is transport of electrons from NADH to ubiquinone. Reason: Correct core process; redundant with the IMP/IBA annotations to GO:0006120. 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... | ACCEPT | Summary: NAS annotation to the Complex I catalytic activity, based on the NADH:ubiquinone oxidoreductase characterization. Redundant with the experimentally supported GO:0008137 annotations. Reason: Correct core molecular function of the complex to which NDUFS8 belongs. Supporting Evidence: PMID:9878551 NADH:ubiquinone oxidoreductase (complex I) |
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Download this section (compressed HTML)Q: Do the two NDUFS8-coordinated [4Fe-4S] clusters correspond specifically to N6a and N6b in the electron-transfer wire of human Complex I, and does either directly gate electron transfer to N2/ubiquinone?
Q: Is the NDUFS8-RAB5IF (C20orf24/Q9BUV8) interaction a stable assembly/regulatory interaction, and does it warrant a more specific molecular-function annotation than protein binding?
Experiment: Site-directed mutagenesis of the eight cluster-ligating cysteines followed by EPR to assign the N6a/N6b clusters to NDUFS8 and measure their redox potentials and role in electron transfer.
Experiment: Blue-native PAGE and cryo-EM of NDUFS8-knockout cells reconstituted with wild-type versus patient-variant NDUFS8 to define which assembly intermediate stalls and quantify the catalytic contribution of each Fe-S cluster.
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