Gene Ontology annotation through association of InterPro records with GO terms
-
InterPro2GO mapping of the NADH:ubiquinone oxidoreductase 51 kDa subunit signatures (IPR011538 Nuo51_FMN-bd, IPR011537, IPR019575), the source of the FMN-binding and NAD-binding electronic annotations. Both map to real, structurally resolved sites on NDUFV1, so domain-based transfer is reliable here.
Annotation inferences using phylogenetic trees
-
Source of the PANTHER phylogenetically-inferred (IBA) annotations for NDUFV1. Only two IBA lines reach this gene - complex I membership and NADH-to-ubiquinone electron transport - and no IBA covers the molecular functions (FMN binding, NAD binding, electron transfer activity) that are the distinguishing features of the 51 kDa flavoprotein subunit.
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
-
UniProtKB keyword-to-GO mapping (KW-0560 Oxidoreductase, KW-0679 Respiratory chain, KW-0479 Metal-binding, KW-0411 Iron-sulfur), contributing correct but broad parent terms that are subsumed by the more specific structural and cofactor annotations.
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Combined Automated Annotation using Multiple IEA Methods
-
Combined multi-method IEA pipeline, converging on complex I membership, inner-membrane location, NADH-to-ubiquinone electron transport and [4Fe-4S] cluster binding, in agreement with the structural and manual evidence.
Chromosomal localization of the human gene encoding the 51-kDa subunit of mitochondrial complex I (NDUFV1) to 11q13.
-
NDUFV1 encodes the 51-kDa flavoprotein subunit of Complex I, which forms the NADH-binding site and is the principal site of electron entry from NADH into the respiratory chain. The gene maps to chromosome 11q13.
"plays an important role in the formation of the NADH-binding site and is believed to be the principal site of entry for electrons donated by NADH into the respiratory chain"
cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed.
-
Complex I functions in electron transport from NADH to ubiquinone, coupled to proton translocation from the mitochondrial matrix to the intermembrane space. Human Complex I consists of 41 subunits (now known to be 45), 34 nuclear-encoded.
"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, which is accompanied by translocation of protons from the mitochondrial matrix to the intermembrane space."
Human complex I defects can be resolved by monoclonal antibody analysis into distinct subunit assembly patterns.
-
Monoclonal antibody and sucrose gradient analysis of Complex I deficient patients including NDUFV1 mutants reveals distinct subunit assembly patterns. NDUFV1 defects can be distinguished from assembly factor defects using this approach.
"the other patients had defects in NDUFV1, NDUFS2 (two patients), NDUFS4 (two patients), NDUFS7, and NDUFS8. We show here that Western blotting with these antibodies, particularly when used in conjunction with sucrose gradient studies and enzymatic activity measurements, helps distinguish catalytic versus assembly defects"
The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification.
-
NDUFV1 was directly identified as a Complex I subunit by immunopurification and mass spectrometry (MALDI-TOF and LC-MS/MS). The study resolved 42 polypeptides from immunoisolated human Complex I.
"we can resolve and identify the human homologues of 42 polypeptides detected so far in the more extensively studied beef heart complex I"
TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial complex I assembly factor through association with the MCIA complex.
-
Interaction proteomics of 15 core CI subunits and assembly factors identified TIMMDC1 as a new CI assembly factor. NDUFV1 was among the core subunits used as baits, and its interaction with NDUFV3 was detected.
"We employed interaction proteomics to interrogate the molecular associations of 15 core subunits and assembly factors previously linked to human CI deficiency, resulting in a network of 101 proteins and 335 interactions"
Cyclin B1/Cdk1 coordinates mitochondrial respiration for cell-cycle G2/M progression.
-
Cyclin B1/Cdk1 localizes to the mitochondrial matrix and phosphorylates Complex I subunits including NDUFV1, enhancing CI activity and mitochondrial respiration for G2/M cell cycle progression. Deficiency of phosphorylation impairs CI function.
"Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function. Mitochondria-targeted cyclin B1/Cdk1 increases mitochondrial respiration with enhanced oxygen consumption and ATP generation"
Architecture of Human Mitochondrial Respiratory Megacomplex I(2)III(2)IV(2).
-
Cryo-EM structure of the human respiratory megacomplex I2III2IV2 at 3.4A resolution. NDUFV1 (residues 27-457) was directly resolved within Complex I. The structure confirms NDUFV1 contains FMN and one [4Fe-4S] cluster. UniProt cites this reference for NDUFV1's function, catalytic activity (EC 7.1.1.2), cofactors, and subunit composition.
"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"
Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.
-
Crosslinking mass spectrometry in intact nuclei detected NDUFV1-NDUFV3 crosslinks, reflecting their close physical proximity within the FP subcomplex of Complex I.
"we use crosslinking mass spectrometry (XL-MS) to chart the protein-protein interactions in intact human nuclei"
Assembly of mammalian oxidative phosphorylation complexes I-V and supercomplexes.
-
Review of OXPHOS complex assembly. Complex I is built in a stepwise fashion through the actions of several assembly factors. The N-module (containing NDUFV1, NDUFV2, NDUFS1) is assembled as the last major module to join the growing complex.
"The assembly of the five oxidative phosphorylation system (OXPHOS) complexes in the inner mitochondrial membrane is an intricate process"
Rewiring of the Human Mitochondrial Interactome during Neuronal Reprogramming Reveals Regulators of the Respirasome and Neurogenesis.
-
Mitochondrial interaction maps generated by co-fractionation mass spectrometry identified NDUFV1 in Complex I. The study also found NDUFV1 interacts with RAB5IF (C20orf24/Q9BUV8), a newly identified respirasome assembly factor.
"using mass spectrometry-based co-fractionation profiles and phosphoproteomics, we generated mitochondrial interaction maps of human pluripotent embryonal carcinoma stem cells and differentiated neuronal-like cells"
A reference map of the human binary protein interactome.
-
HuRI is a systematic yeast two-hybrid map of binary human protein interactions; the NDUFV1-CYSRT1 pairing annotated from it is one such systematic hit, made in a heterologous assay that places both proteins outside their native compartments, and carries no functional claim about NDUFV1.
"yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs"
-
The authors note that most HuRI interactions were detected in only a single screen, which is the relevant caveat for reading an isolated, biologically unexplained pairing such as NDUFV1-CYSRT1.
"the majority of PPIs in HuRI were found in only one screen"
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
-
Large-scale interactome mapping detected multiple NDUFV1 protein-protein interactions including with proteasome subunits (PSMB1, PSMA3, PSMD5), signaling proteins (PRKCA, YWHAG), and many others. Many of these interactions are of unclear biological significance for a mitochondrial Complex I subunit.
"we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening"
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
-
Dual proteome-scale network study confirmed NDUFV1-NDUFV3 interaction, consistent with both being subunits of the FP subcomplex within Complex I.
"Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
-
NDUFV1 was identified in the high-confidence human mitochondrial proteome by quantitative mass spectrometry, confirming its mitochondrial localization.
"We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)"
Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2
NUBPL transfers 4Fe-4S to NDUFV1, V2
Peripheral arm subunits bind the 815kDa complex to form a 980kDa complex
-
Late assembly step in which the flavoprotein peripheral-arm subunits, NDUFV1 among them, join the membrane-anchored 815 kDa intermediate. The N-module is added last, which is why NDUFV1 loss leaves partially assembled complex I rather than abolishing assembly outright.
The MCIA complex, NDUFAF2-7 all dissociate from the 980kDa complex, resulting in Complex I
NDUF subunits bind to form the FP subcomplex
-
Formation of the flavoprotein (FP) subcomplex from NDUFV1, NDUFV2 and NDUFV3, the assembly context for the observed NDUFV1-NDUFV3 interactions reported by several interaction-proteomics studies cited here.
LONP1 binds mitochondrial inner membrane proteins
LONP1 degrades mitochondrial inner membrane proteins
Deep research review of NDUFV1 gene function (Falcon provider)
-
NDUFV1 is the 51 kDa FMN-binding core subunit of mitochondrial Complex I located in the N-module at the matrix-facing tip of the peripheral arm. It catalyzes NADH oxidation as the initial electron acceptor and passes electrons through Fe-S clusters to ubiquinone. The reduced FMN site is the predominant source of ROS from Complex I. Biallelic mutations cause MC1DN4/Leigh syndrome.
"NDUFV1 binds FMN as the primary electron acceptor for NADH and harbors canonical motifs that support NADH/FMN and Fe-S relay connectivity at the N-module interface. Electrons flow NADH to FMN (bound in NDUFV1) to series of Fe-S clusters to terminal cluster N2 near the ubiquinone site."