Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.
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
Electronic Gene Ontology annotations created by ARBA machine learning models
Characterization of the mammalian initiation factor eIF2B complex as a GDP dissociation stimulator protein.
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Demonstrated that eIF2B acts as a GDP dissociation stimulator protein
"mammalian eIF2B can mediate release of eIF2-bound GDP even in the absence of free nucleotide, indicating that it acts as a GDP dissociation stimulator protein"
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Showed that all five subunits contribute to full activity
"It is composed of five subunits, alpha-epsilon."
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Confirmed eIF2B mediates release of eIF2-bound GDP
"Initiation factor eIF2B mediates a key regulatory step in the initiation of mRNA translation, i.e. the regeneration of active eIF2.GTP complexes."
A severe variant of childhood ataxia with central hypomyelination/vanishing white matter leukoencephalopathy related to EIF21B5 mutation.
Reduced amino acid availability inhibits muscle protein synthesis and decreases activity of initiation factor eIF2B.
eIF2B-related disorders: antenatal onset and involvement of multiple organs.
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Described severe prenatal forms of eIF2B-related disease
"eIF2B-related disorders: antenatal onset and involvement of multiple organs"
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Showed multi-organ involvement
"eIF2B-related disorders: antenatal onset and involvement of multiple organs"
Decreased guanine nucleotide exchange factor activity in eIF2B-mutated patients.
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Measured 20-70% decrease in GEF activity in patient cells
"A significant decrease of 20-70% in GEF activity was observed in all mutated cells"
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Correlated GEF activity decrease with disease severity
"The severity of this decrement of GEF activity correlated with age at onset of the disease"
Mutations linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways.
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Characterized functional effects of VWM mutations on eIF2B
"Mutations linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways"
The life and death of oligodendrocytes in vanishing white matter disease.
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Documented oligodendrocyte pathology in VWM
"Vanishing white matter disease (VWM) is a progressive cavitating disease of central white matter due to a deficiency of the translation initiation factor eIF2B"
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Showed both apoptosis and proliferation of oligodendrocytes
"Oligodendrocytes appear to be numerically increased in some white matter areas, while decreased in others"
Screening for known mutations in EIF2B genes in a large panel of patients with premature ovarian failure.
An efficient mammalian cell-free translation system supplemented with translation factors.
A proteome-scale map of the human interactome network.
Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound.
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Identified eIF2B as the target of ISRIB
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Showed mutations in delta subunit affect ISRIB response
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Demonstrated ISRIB stimulates eIF2B GEF activity
Widespread macromolecular interaction perturbations in human genetic disorders.
Expression, purification, and crystallization of Schizosaccharomyces pombe eIF2B.
Comparative influenza protein interactomes identify the role of plakophilin 2 in virus restriction.
Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.
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Solved atomic structure of human eIF2B with ISRIB
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Showed decameric assembly is required for full activity
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Demonstrated ISRIB stabilizes decameric form
Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
T-cell activation leads to rapid stimulation of translation initiation factor eIF2B and inactivation of glycogen synthase kinase-3.
Formation of eIF2:GDP:eIF2B intermediate
Deep research on EIF2B4 function
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Comprehensive review of eIF2B structure and function
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Documented role in integrated stress response
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Described subcellular localization to cytosol and eIF2B bodies
Falcon deep research on EIF2B4 function
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EIF2B4/eIF2Bdelta is a regulatory/scaffold subunit (not catalytic) that supports decameric holoenzyme assembly and contributes to the beta/delta core central to allosteric regulation
"eIF2B's catalytic function is mainly attributed to the γ and ε subunits, while α/β/δ enhance full activity and provide regulatory control, including stress sensitivity"
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Phospho-eIF2alpha binds an interface that includes EIF2B4 (delta) and blocks engagement of eIF2gamma with the catalytic epsilon subunit
"phosphorylated eIF2α binds eIF2B in a way that blocks productive engagement of eIF2γ with the catalytic ε subunit, suppressing nucleotide exchange"
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eIF2B localizes to discrete cytoplasmic eIF2B bodies with cell-type-specific composition
"eIF2B localizes to discrete cytoplasmic foci called eIF2B bodies, which are interpreted as sites of eIF2B GEF activity and exhibit cell-type-specific composition in neuronal and glial cell lines"
Analysis of the subunit organization of the eIF2B complex reveals new insights into its structure and regulation.
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Established eIF2B as heterodecamer that is a dimer of tetramers stabilized by additional subunits
"is actually decameric, a dimer of eIF2B(βγδε) tetramers stabilized by 2 copies"
Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response.
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Authoritative ISR review documenting that eIF2alpha phosphorylation inhibits eIF2B GEF activity
"Phosphorylation of eIF2α (p-eIF2α) blocks the eIF2B-directed exchange, consequently reducing the levels of eIF2•GTP that are required for delivery of methionyl initiator tRNA"
eIF2Bdelta blocks the integrated stress response and maintains eIF2B activity and cancer metastasis by overexpression in breast cancer stem cells.
Ovarioleukodystrophy Due to EIF2B Genes: Systematic Review and Case Report.
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Systematic review of 20 worldwide ovarioleukodystrophy cases highlighting EIF2B4 involvement
"This resulted in a series of 20 cases of women with ovarioleukodystrophy due to variants in the EIF2B gene complex. The median age of onset was 19 years (range 0.6-40)"
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Reported new case with homozygous EIF2B4 c.725C>T (p.Pro242Leu)
"identified the variant c.725C>T (NM_015636.3; p.Pro242Leu) in the EIF2B4 gene in a homozygous state"
eIF2B localization and its regulation during the integrated stress response is cell-type specific.
Genotypic and phenotypic heterogeneity among Chinese pediatric genetic white matter disorders.