Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Combined Automated Annotation using Multiple IEA Methods
Characterization of the human complex I NDUFB7 and 17.2-kDa cDNAs and mutational analysis of 19 genes of the HP fraction in complex I-deficient-patients.
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The cDNA encoding the human Complex I 17.2-kDa subunit (B17.2, now NDUFA12) was characterized as part of an effort to complete the inventory of the 36 expected nuclear-encoded structural Complex I genes, placing it in the hydrophobic (HP) fraction of the complex.
"17.2-kDa cDNA sequences of the hydrophobic (HP) fraction of the complex."
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Screening the HP-fraction subunits in 14 unexplained Complex I-deficient patients found no pathogenic mutations, so this paper provides no functional or enzymological characterization of the 17.2-kDa protein itself.
"mutations in those 14 patients of our initial patient cohort in whom the"
The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification.
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Immunocapture of human Complex I followed by 1D/2D gel electrophoresis, MALDI-TOF peptide mass fingerprinting and nanoflow LC-MS/MS resolved 42 polypeptides, matching the subunit inventory of the better-characterized bovine complex.
"homologues of 42 polypeptides detected so far in the more extensively studied"
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Among the identified subunits is the protein associated with differentiation-linked processes, i.e. the 13 kDa differentiation-associated protein DAP13/NDUFA12, establishing it as a constituent of the mature human Complex I holoenzyme.
"differentiation linked processes"
Cyclin B1/Cdk1 coordinates mitochondrial respiration for cell-cycle G2/M progression.
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A pool of cyclin B1/Cdk1 localizes to the mitochondrial matrix and phosphorylates Complex I subunits, so Complex I subunits are substrates of a cell-cycle kinase.
"mitochondrial proteins, including the complex I (CI) subunits in the respiratory"
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Phosphorylation of the relevant CI subunits raises Complex I activity, and blocking it in any one of those subunits impairs CI function - the basis for the complex-level electron-transport IMP annotations on NDUFA12.
"Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas"
Accessory subunits are integral for assembly and function of human mitochondrial complex I.
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Human complex I comprises 45 subunits, of which only 14 core subunits are shared with bacteria and essential for catalysis; the role of the remaining 31 accessory subunits, NDUFA12 among them, was previously unclear.
"mitochondrial respiratory chain and is composed of 45 subunits in humans, making"
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Knockout cell lines were generated by gene editing for every accessory subunit and profiled by quantitative proteomics; 25 accessory subunits proved strictly required for assembly of a functional complex.
"Here we use gene editing to generate human knockout"
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Loss of any given subunit destabilized the other subunits of the same structural module, which is how this study assigns each accessory subunit - including NDUFA12 - to a module of the complex.
"of each subunit affects the stability of other subunits residing in the same"
Architecture of Human Mitochondrial Respiratory Megacomplex I(2)III(2)IV(2).
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Cryo-EM of the human respiratory megacomplex I2III2IV2 resolved 140 subunits together with associated cofactors, providing the structural context in which individual Complex I subunits were located.
"chain megacomplex-I2III2IV2 (MCI2III2IV2) with 140 subunits and a subset of"
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The structure gives a precise, individual assignment of the subunits of human Complex I, which is the basis for the ComplexPortal IDA/IPI annotations placing NDUFA12 in Complex I in the inner membrane.
"The structure not only reveals the precise assignment of individual subunits of"
Assembly of mammalian oxidative phosphorylation complexes I-V and supercomplexes.
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In the OXPHOS complexes the catalytic work is done by a set of core proteins, while the numerous supernumerary subunits - the class NDUFA12 belongs to - serve assembly, regulation and stability roles.
"supernumerary' subunits that play essential roles in assembly, regulation"
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Complexes I, III and IV associate into respiratory supercomplexes or respirasomes, the higher-order context in which Complex I subunits such as NDUFA12 operate.
"established that complexes I, III and IV interact with each other, forming the"
A reference map of the human binary protein interactome.
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HuRI (HI-III-20) is a systematic all-by-all yeast two-hybrid screen of ~90% of the protein-coding genome, yielding 52,569 verified binary PPIs among 8,275 proteins; this is the screen that reports the NDUFA12 interactions (TMED8, MYO15B, SYT4).
"we refer to HI-III-20 as a reference map of the human binary protein interactome (HuRI)"
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The authors state that the cellular function of most individual PPIs in the map remains unknown, which is why a HuRI-derived 'protein binding' annotation carries no functional information about NDUFA12.
"the cellular function of most individual PPIs remains to be elucidated"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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Over 8,000 proteins were classified in mitochondrial preparations of human cells to define MitoCoP, a high-confidence mitochondrial proteome of more than 1,100 proteins; NDUFA12's presence in this inventory supports its mitochondrial localization.
"mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)"
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The dataset is quantitative and covers protein abundance over six orders of magnitude, but it is an organelle-level inventory and does not resolve submitochondrial compartment, so it cannot support the inner-membrane term.
"The abundance of MitoCoP proteins covers six orders of"
Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2
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Reactome describes Complex I as an L-shaped 45-subunit enzyme whose IP and FP fractions protrude into the matrix while the HP arm lies within the inner mitochondrial membrane, with FMN and eight Fe-S clusters carrying the electrons from NADH to ubiquinone - the catalytic machinery NDUFA12 lacks.
"the HP arm lying within the inner mitochondrial membrane"
Peripheral arm subunits bind the 815kDa complex to form a 980kDa complex
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NDUFA12 is placed by Reactome in the peripheral (flavoprotein, FP) arm subcomplex that joins the 815 kDa Complex I assembly intermediate, alongside NDUFS1/4/6 and NDUFV1/2/3 and the assembly factor NDUFAF2.
"Subunits NDUFA12, NDUFS1, 4, 6, NDUFV1, 2 and 3 with the assembly factor"
The MCIA complex, NDUFAF2-7 all dissociate from the 980kDa complex, resulting in Complex I
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The final step of Reactome's Complex I biogenesis pathway has the assembly factors, including NDUFA12's paralog NDUFAF2, dissociate from the 980 kDa intermediate to yield mature Complex I - the distinction between assembly factors and true subunits such as NDUFA12.
"The MCIA complex, NDUFAF2-7 all dissociate from the 980kDa complex"
NDUF subunits bind to form the FP subcomplex
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Reactome models the formation of the flavoprotein (FP) subcomplex from NDUF subunits as a discrete step of Complex I biogenesis, the module to which NDUFA12 is assigned.
"NDUF subunits bind to form the FP subcomplex"