Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Electronic Gene Ontology annotations created by ARBA machine learning models
Falcon deep research synthesis for human NDUFS4
Human complex I defects can be resolved by monoclonal antibody analysis into distinct subunit assembly patterns.
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Monoclonal antibody analysis and sucrose gradient studies of NDUFS4 mutant patient cells showed distinct subunit assembly defects, demonstrating NDUFS4 is required for normal Complex I assembly.
"Western blotting with these antibodies, particularly when used in conjunction with sucrose gradient studies and enzymatic activity measurements, helps distinguish catalytic versus assembly defects and further distinguishes between mutations in different subunits"
Mutation in the NDUFS4 gene of complex I abolishes cAMP-dependent activation of the complex in a child with fatal neurological syndrome.
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NDUFS4 mutation abolishes cAMP-dependent phosphorylation of the NDUFS4 protein and cAMP-dependent activation of Complex I, showing for the first time that human Complex I is regulated via phosphorylation of NDUFS4.
"the homozygous 5 bp duplication in the cDNA of the NDUFS4 18 kDa subunit of complex I abolishes cAMP-dependent phosphorylation of this protein and activation of the complex. These findings show for the first time that human complex I is regulated via phosphorylation of the subunit encoded by the NDUFS4 gene."
A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome.
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Nonsense mutation in NDUFS4 causes complete absence of normally assembled Complex I in the inner mitochondrial membrane, severe reduction of NADH:UQ oxidoreductase activity, and insensitivity to cAMP stimulation, demonstrating that NDUFS4 is essential for assembly of a functional Complex I.
"Two-dimensional electrophoresis showed the absence of detectable normally assembled complex I in the inner mitochondrial membrane. These findings show that the expression of the NDUFS4 gene is essential for the assembly of a functional complex I."
The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification.
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NDUFS4 was identified as a subunit of human Complex I by immunocapture followed by MALDI-TOF and LC-MS/MS mass spectrometry.
"we can resolve and identify the human homologues of 42 polypeptides detected so far in the more extensively studied beef heart complex I"
Clinical heterogeneity in patients with mutations in the NDUFS4 gene of mitochondrial complex I.
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Marked clinical heterogeneity exists among patients with NDUFS4 mutations, including neurological presentations consistent with Leigh syndrome, even among patients with the same genotype.
"A comparison of the clinical presentation, disease course and results of laboratory and imaging studies of all patients so far published with a NDUFS4 mutation are presented. This reveals marked clinical heterogeneity, even in patients with the same genotype."
Respiratory complex I in brain development and genetic disease.
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All NDUFS4 mutations studied resulted in impairment of Complex I assembly. Complex I expression and activity markedly increase during brain cell differentiation.
"All the NDUFS4 mutations resulted in impairment of the assembly of a functional complex"
Dysfunctions of cellular oxidative metabolism in patients with mutations in the NDUFS1 and NDUFS4 genes of complex I.
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NDUFS4 G44A nonsense mutation prevents complete Complex I assembly and fully suppresses activity. Unlike NDUFS1 mutation, no ROS increase was observed with the NDUFS4 mutation.
"the NDUFS4 mutation prevented complete assembly of the complex and caused full suppression of the activity...No ROS increase was observed in the NDUFS4 mutation"
cAMP controls oxygen metabolism in mammalian cells.
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NDUFS4 missense defect suppresses Complex I activity and prevents ROS production. cAMP activates NADH-ubiquinone oxidoreductase activity, and this activation is abolished by NDUFS4 mutation.
"A missense genetic defect in the NDUFS4 subunit, putative substrate of PKA, suppressed, on the other hand, the activity of the complex and prevented ROS production"
Accessory subunits are integral for assembly and function of human mitochondrial complex I.
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Systematic gene editing study showed 25 of 31 accessory subunits (including NDUFS4) are strictly required for assembly of a functional Complex I. Loss of each subunit affects stability of other subunits in the same structural module.
"We show that 25 subunits are strictly required for assembly of a functional complex and 1 subunit is essential for cell viability"
Architecture of Human Mitochondrial Respiratory Megacomplex I(2)III(2)IV(2).
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Cryo-EM structure of the human respiratory megacomplex at 3.4 A resolution reveals precise assignment of all Complex I subunits including NDUFS4 in the mitochondrial inner membrane.
"The structure not only reveals the precise assignment of individual subunits of human CI and CIII, but also enables future in-depth analysis of the electron transport chain as a whole"
Assembly of mammalian oxidative phosphorylation complexes I-V and supercomplexes.
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Review of the assembly pathways for all five OXPHOS complexes. Complex I assembly involves multiple intermediate stages with numerous assembly factors, and supernumerary subunits play essential roles in assembly, regulation, and stability.
"The assembly of the five oxidative phosphorylation system (OXPHOS) complexes in the inner mitochondrial membrane is an intricate process"
BAP31 regulates mitochondrial function via interaction with Tom40 within ER-mitochondria contact sites.
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BAP31 interacts with NDUFS4 and Tom40 to form an ER-mitochondria bridging complex that stimulates translocation of NDUFS4 from the cytosol to mitochondria. Loss of BAP31 reduces NDUFS4 in the mitochondrial fraction and suppresses Complex I activity.
"BAP31 interacts with mitochondria-localized proteins, including Tom40, to stimulate the translocation of NDUFS4, the component of complex I from the cytosol to the mitochondria"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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NDUFS4 identified as part of the high-confidence human mitochondrial proteome by quantitative proteomics.
"Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context"
Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit.
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First report of NDUFS4 cDNA cloning, chromosomal localization (chromosome 5), and identification of a pathogenic homozygous 5-bp duplication destroying a consensus phosphorylation site, causing Complex I deficiency.
"We report the cDNA cloning, chromosomal localization, and a mutation in the human nuclear gene encoding the 18-kD (AQDQ) subunit of the mitochondrial respiratory chain complex I...A homozygous 5-bp duplication, destroying a consensus phosphorylation site"
cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed.
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Completed characterization of all nuclear-encoded Complex I subunit cDNAs. NDUFS4 encodes the 18 kDa subunit of NADH:ubiquinone oxidoreductase.
"NADH:ubiquinone oxidoreductase (complex I) is an extremely complicated multiprotein complex located in the inner mitochondrial membrane. Its main function is the transport of electrons from NADH to ubiquinone"
Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2
Peripheral arm subunits bind the 815kDa complex to form a 980kDa complex
The MCIA complex, NDUFAF2-7 all dissociate from the 980kDa complex, resulting in Complex I
NDUF subunits bind to form the FP subcomplex