Affinage

EIF2B3

Translation initiation factor eIF2B subunit gamma · UniProt Q9NR50

Round 2 corrected
Length
452 aa
Mass
50.2 kDa
Annotated
2026-04-28
74 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EIF2B3 encodes the γ subunit of eIF2B, a heterodecameric guanine nucleotide exchange factor (GEF) that catalyzes GDP-to-GTP exchange on eIF2, a rate-limiting step in translation initiation (PMID:7893825, PMID:29599213). The γ subunit contributes to holoenzyme assembly through its pyrophosphorylase-like and left-handed β-helix domains, which form extensive contacts with the catalytic ε subunit (PMID:22238343); catalytic GEF activity resides in the ε subunit and is regulated by eIF2α phosphorylation (converting eIF2 into a competitive inhibitor of eIF2B), by GSK-3–mediated phosphorylation of ε Ser-535, and by ISRIB binding at the β–δ interface that promotes decameric assembly (PMID:7565788, PMID:8007958, PMID:25858979, PMID:29599245). Loss-of-function mutations in EIF2B3 cause vanishing white matter disease (leukoencephalopathy), characterized by defective myelination, impaired integrated stress responses, and dysregulated autophagy in oligodendrocytes (PMID:11835386, PMID:33517449, PMID:26625702).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1984 Medium

    Early reconstitution showed that eIF-2B binding shields eIF-2 phosphorylation sites, establishing that the eIF-2·eIF-2B interaction is structurally intimate enough to alter substrate accessibility for kinases and phosphatases.

    Evidence In vitro addition of purified eIF-2B to phosphorylated eIF-2 in reticulocyte lysate with kinase/phosphatase assays

    PMID:6088496

    Open questions at the time
    • Stoichiometry and binding interface unknown at this stage
    • Physiological relevance of shielding not tested in cells
  2. 1987 High

    Polysome profiling revealed that phospho-eIF-2α blocks eIF-2B-mediated GDP release from eIF-2 on ribosomes, trapping initiation complexes — this defined the mechanistic step at which translational inhibition occurs.

    Evidence Sedimentation analysis and Met-tRNA binding assays in reticulocyte lysate with purified eIF-2B add-back

    PMID:3646234

    Open questions at the time
    • Identity and contribution of individual eIF-2B subunits not resolved
    • No structural information on the eIF-2·eIF-2B interface
  3. 1992 Medium

    ER-stress agents were shown to inhibit eIF-2B activity via eIF-2α phosphorylation, extending the regulatory paradigm from heme deficiency to a broader integrated stress response.

    Evidence Thapsigargin/A23187/DTT treatment of GH3 cells with eIF-2B activity and eIF-2α phosphorylation measurements

    PMID:1512215

    Open questions at the time
    • Kinase identity mediating ER-stress-induced eIF-2α phosphorylation not identified
    • Mechanism of chronic recovery unclear
  4. 1993 High

    Identification of GSK-3 as the kinase phosphorylating the ε subunit of eIF-2B linked insulin signalling to translational control: insulin inactivates GSK-3, relieving inhibitory phosphorylation of eIF-2Bε.

    Evidence Mono-S chromatography fractionation of CHO extracts, GSK-3 isoform-specific immunoblotting, phosphatase-2A reversal

    PMID:8397507

    Open questions at the time
    • GSK-3 target site on ε not yet mapped
    • Whether GSK-3 inhibition alone is sufficient for full activation unknown
  5. 1994 High

    Biochemical purification established eIF-2B as a five-subunit (α–ε) GEF, and antibody inhibition experiments demonstrated that the ε subunit is the catalytically essential GEF subunit, while β and δ are dispensable for catalysis per se.

    Evidence Purification to homogeneity from liver, subunit-specific monoclonal antibody inhibition of GEF activity and reticulocyte lysate translation

    PMID:7803480 PMID:7893825 PMID:8168527

    Open questions at the time
    • Functions of non-catalytic subunits (including γ) not defined
    • No atomic structure
  6. 1994 High

    Yeast genetics showed that eIF2Bβ mutations uncouple phospho-eIF-2 sensing from catalytic function, establishing the regulatory subcompllex (α/β/δ) as a distinct functional module sensing eIF-2α phosphorylation.

    Evidence GCD7 suppressor mutations in S. cerevisiae with GCN4-lacZ reporter and mammalian kinase expression

    PMID:8007958 PMID:8164676

    Open questions at the time
    • Molecular contacts between phospho-eIF-2α and the regulatory subcomplex unresolved
    • Role of γ subunit in regulation unclear
  7. 1995 High

    Overexpression of all five eIF-2B subunits in yeast demonstrated that phospho-eIF-2 acts as a competitive inhibitor rather than forming an irreversibly trapped complex, resolving a long-standing mechanistic debate.

    Evidence Gene dosage manipulation in S. cerevisiae with GCN4-lacZ reporters and genetic epistasis

    PMID:7565788

    Open questions at the time
    • Quantitative binding parameters for phospho- vs. non-phospho-eIF-2 not determined
  8. 2000 Medium

    EIF2B3 (γ subunit) was identified as specifically required for HCV IRES-mediated translation but not cap-dependent translation, revealing a subunit-specific role beyond general GEF function.

    Evidence Randomized ribozyme library screen in HeLa cells with bicistronic HCV IRES reporter

    PMID:10900014

    Open questions at the time
    • Mechanism by which γ depletion selectively affects IRES translation not elucidated
    • Confirmed only with ribozymes in one cell line
  9. 2002 High

    Two parallel advances: (1) GSK-3 phosphorylation of eIF2Bε was mapped to Ser-535, but dephosphorylation alone was shown insufficient for insulin-mediated activation, revealing additional regulatory inputs; (2) EIF2B3 mutations were found to cause vanishing white matter disease, establishing the γ subunit as independently disease-causative.

    Evidence GSK-3 inhibitors in CHO cells with phospho-specific antibodies; sequencing of EIF2B genes in VWM patients

    PMID:11835386 PMID:12133000

    Open questions at the time
    • Identity of the additional insulin-responsive input unknown
    • Genotype–phenotype correlations for EIF2B3 mutations incomplete
  10. 2012 Medium

    Domain mapping showed that the pyrophosphorylase-like and left-handed β-helix domains of the γ and ε subunits mediate their association, defining the structural basis for the γ–ε subcomplex within the holoenzyme.

    Evidence Co-expression/co-precipitation of domain constructs in yeast with domain deletion series

    PMID:22238343

    Open questions at the time
    • No atomic-resolution structure of the γ–ε interface
    • Functional consequences of disrupting specific domain contacts not fully tested in mammalian cells
  11. 2015 High

    ISRIB was shown to act by enhancing eIF2B GEF activity through a site on the β/δ regulatory subunits, and VWM-associated mutations in eIF2Bα and EIF2B3 were shown to impair ER stress tolerance and autophagy in oligodendrocytes, connecting eIF2B dysfunction to glial pathology.

    Evidence CRISPR knock-in mutagenesis with in vitro GEF assays for ISRIB; oligodendrocyte transfection with EIF2B3 mutant plus autophagy flux measurements

    PMID:25858979 PMID:26285592 PMID:26625702

    Open questions at the time
    • Structural basis of ISRIB binding not yet resolved
    • Whether autophagy rescue is therapeutically relevant in vivo untested
  12. 2018 High

    Cryo-EM structures of the eIF2B decamer revealed that ISRIB binds a deep cleft at the β–δ symmetry interface and promotes decameric assembly, providing the atomic-level explanation for ISRIB pharmacology and illuminating the architecture of the holoenzyme including the γ subunit position.

    Evidence Cryo-EM at 4.1 Å and atomic resolution from two independent groups, with mutagenesis validation

    PMID:29599213 PMID:29599245

    Open questions at the time
    • Structure of the eIF2B–eIF2 complex not resolved at this point
    • Conformational dynamics of substrate engagement by γ–ε catalytic lobe unknown
  13. 2021 High

    CRISPR-generated zebrafish eif2b3 knockouts recapitulated VWM hallmarks — myelin defects, glial differentiation failure, ISR activation, and ectopic VEGF-driven angiogenesis — and VEGF inhibition partially rescued the vascular phenotype, identifying a potential therapeutic axis.

    Evidence CRISPR mutagenesis in zebrafish with histology, gene expression profiling, and SU5416 pharmacological rescue

    PMID:33517449

    Open questions at the time
    • Whether VEGF dysregulation is a direct or indirect consequence of eIF2B3 loss unknown
    • Translatability of VEGF inhibition to mammalian VWM models not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the specific structural contribution of the γ subunit to phospho-eIF2 sensing and GEF catalysis, the mechanism by which γ-subunit mutations selectively impair oligodendrocyte function, and whether γ-specific therapeutic strategies can complement ISRIB-like approaches for VWM.
  • No high-resolution structure of eIF2B–phospho-eIF2 complex with γ contacts mapped
  • Cell-type-specific vulnerability of oligodendrocytes to EIF2B3 mutations mechanistically unexplained
  • No therapeutic rescue of EIF2B3-specific mutations demonstrated in mammalian disease models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1643685 Disease 2
Partners
EIF2B1EIF2B2EIF2B4EIF2B5EIF2S1
Complex memberships
eIF2B

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 GSK-3 phosphorylates the largest (epsilon) subunit of eIF-2B and is rapidly inactivated by insulin, linking insulin signalling to eIF-2B activation through GSK-3 inhibition. Mono-S chromatography of CHO cell extracts, immunoblotting with GSK-3 isoform-specific antibodies, peptide kinase assays, protein phosphatase-2A reversal experiments The Biochemical journal High 8397507
1992 Agents that disrupt ER calcium homeostasis (thapsigargin, A23187, DTT) cause phosphorylation of eIF-2α and a ~50% reduction in eIF-2B activity, inhibiting translational initiation; chronic exposure leads to recovery coincident with eIF-2α dephosphorylation. Intact GH3 cell treatment, eIF-2B activity assay, isoelectric focusing to measure eIF-2α phosphorylation The Journal of biological chemistry Medium 1512215
1995 In yeast, overexpression of all five subunits of eIF-2B suppresses eIF-2α hyperphosphorylation effects on general and GCN4-specific translation; phosphorylated eIF-2 acts as a competitive inhibitor of eIF-2B rather than forming an irreversibly inhibitory complex. Gene dosage experiments (overexpression and deletion of eIF-2B subunit genes in S. cerevisiae), GCN4-lacZ reporter assays, genetic epistasis Molecular and cellular biology High 7565788
1994 eIF-2B is a heteropentamer (α, β, γ, δ, ε subunits) functioning as a guanine nucleotide exchange factor for eIF-2; it promotes release of GDP from eIF-2·GDP, enabling formation of active eIF-2·GTP. The ε subunit is catalytically essential, and phosphorylation of eIF-2α inhibits eIF-2B activity. Biochemical purification, guanine nucleotide exchange assays, review of cloning data and functional complementation studies Biochimie High 7893825
2000 EIF2Bγ (the gamma subunit of eIF2B) is required for HCV IRES-mediated translation; ribozymes targeting EIF2Bγ mRNA inhibit IRES-dependent translation of HCV core protein without affecting cap-dependent translation. Randomized hairpin ribozyme library selection in HeLa cells stably expressing bicistronic HCV IRES reporter, ganciclovir/hygromycin selection, functional validation with additional ribozymes Proceedings of the National Academy of Sciences of the United States of America Medium 10900014
1996 Glucose stimulates eIF-2B guanine nucleotide exchange activity in isolated rat islets of Langerhans within 15 min, over the same concentration range that stimulates insulin synthesis, via a mechanism independent of eIF-2α phosphorylation. eIF-2B activity assay in isolated rat islets, eIF-2α phosphorylation measured by isoelectric focusing/immunoblot, mannoheptulose as non-metabolizable control The Journal of biological chemistry Medium 8567668
1994 Purified rat and bovine liver eIF-2B is a five-subunit complex (30.9–89.1 kDa); protein kinase activity in rat liver extracts phosphorylates only the ε subunit of eIF-2B. Quantitative immunoassay shows eIF-2B:eIF-2 ratios of ~0.6 (liver) and ~0.3 (reticulocytes). Biochemical purification to >95% homogeneity, monoclonal antibody generation, kinase assays with purified eIF-2B as substrate, quantitative immunoblotting Biochimica et biophysica acta High 7803480
1994 Mutations in the GCD7 (β) subunit of yeast eIF-2B overcome inhibition by phosphorylated eIF-2α without impairing catalytic GEF function, demonstrating that GCD7/eIF2Bβ plays a key role in the regulatory interaction between phospho-eIF-2 and eIF-2B. Suppressor mutation screen in S. cerevisiae, GCN4-lacZ reporter assays, growth assays under amino acid starvation and with constitutively active GCN2c kinase, expression of mammalian dsRNA-PK Molecular and cellular biology High 8164676
1994 Anti-ε monoclonal antibody inhibits eIF-2B guanine nucleotide exchange activity and protein synthesis at the initiation level in reticulocyte lysate; anti-β and anti-δ antibodies do not, establishing the ε subunit as essential for catalytic GEF activity. Monoclonal antibody inhibition assays of eIF-2B GEF activity and reticulocyte lysate translation, Western blotting, ELISA, immunoprecipitation European journal of biochemistry High 8168527
1994 Phosphorylation of eIF-2α at Ser-51 by HRI kinase inhibits eIF-2B GEF activity; Ser-48 in eIF-2α maintains high affinity between phospho-eIF-2 and eIF-2B, thereby inactivating eIF-2B. Expression of 51A mutant eIF-2α protects eIF-2B from inhibition. Overexpression of wild-type and mutant eIF-2α (S48A, S51A) in CHO cells, addition of purified HRI kinase to cell extracts, eIF-2B GEF activity assays, heat-shock experiments Molecular and cellular biology High 8007958
2002 GSK-3 phosphorylates eIF2Bε at Ser-535 in vivo; dephosphorylation of Ser-535 alone is insufficient for insulin-mediated activation of eIF2B, indicating additional regulatory inputs are required beyond GSK-3 inactivation. Site-specific phosphorylation analysis, GSK-3 inhibitors (LiCl, SB-415286, SB-216763) in CHO cells, eIF2B activity assays, phospho-specific antibodies The Biochemical journal High 12133000
2000 EGF- and NGF-induced activation of eIF2B in PC12 cells requires MEK/ERK signalling (blocked by PD98059), and this occurs without detectable dephosphorylation of the GSK-3 site Ser-535 in eIF2Bε, revealing a GSK-3-independent activation pathway. PC12 cell treatment with EGF/NGF ± MEK inhibitor PD98059, eIF2B activity assays, phospho-Ser535 immunoblotting, GSK-3 activity measurement FEBS letters Medium 10913625
1987 Phosphorylation of eIF-2α prevents eIF-2B-mediated dissociation of eIF-2·GDP from the 60S ribosomal subunit of complete initiation complexes, causing accumulation of eIF-2 on polysomes and a shift from 43S to 48S pre-initiation complexes; exogenous eIF-2B reverses these effects. Rabbit reticulocyte lysate sedimentation analysis, polysome profiling, Met-tRNA binding assays, addition of exogenous purified eIF-2B The Journal of biological chemistry High 3646234
1988 Sugar phosphates (glucose 6-phosphate, fructose 1,6-diphosphate) are required for eIF-2B activity by a mechanism independent of eIF-2α phosphorylation, suggesting a direct allosteric effect of sugar phosphates on eIF-2B function. Gel-filtered reticulocyte lysate translation assays, eIF-2B GDP dissociation assays, antibody neutralization of HCR kinase, isoelectric focusing for eIF-2α phosphorylation The Journal of biological chemistry Medium 2842334
1984 When eIF-2 is complexed with eIF-2B, dephosphorylation of eIF-2α is inhibited 75% and phosphorylation of eIF-2β cannot be detected, whereas Met-tRNAi·GTP ternary complex formation specifically protects eIF-2β from dephosphorylation; these results show that eIF-2B and Met-tRNAi regulate accessibility of eIF-2 phosphorylation/dephosphorylation sites. Addition of doubly phosphorylated eIF-2 to reticulocyte lysate and purified phosphatase, kinase assays on eIF-2·eIF-2B complex, ternary complex formation assays The Journal of biological chemistry Medium 6088496
1991 eIF-2B-catalyzed conversion of eIF-2·GDP to eIF-2·GTP requires Met-tRNAi(fMet) (not tRNAi alone) for efficient GDP-to-GTP exchange; without Met-tRNAi, eIF-2B can dissociate GDP but cannot efficiently drive formation of the eIF-2·GTP complex. In vitro guanine nucleotide exchange assays with purified eIF-2 and eIF-2B, [3H]GDP release assays, ternary complex reconstitution Biochemical and biophysical research communications Medium 1764100
1995 eIF-2B from calf brain is a five-subunit GEF complex (82, 65, 52, 42, 30 kDa) whose exchange activity is inhibited by N-ethylmaleimide; a 37-kDa calmodulin-binding protein co-purifies with the initiation factors from brain. Biochemical purification from brain (heparin-Sepharose, SP-5PW, DEAE-5PW HPLC), GEF activity assays, ternary complex assays, NEM inhibition Journal of neurochemistry Medium 7616232
2012 The pyrophosphorylase-like domains (PLDs) and left-handed β-helix (LβH) domains of eIF2Bγ and eIF2Bε mediate extensive intersubunit interactions required for eIF2Bγ–ε subcomplex formation and overall eIF2B complex assembly; a potential nucleotide-binding region in the eIF2Bε PLD does not significantly contribute to nucleotide exchange catalysis. Co-expression and co-precipitation of domain constructs in yeast, genetic interaction analysis, domain deletion series The Journal of biological chemistry Medium 22238343
1995 The rat eIF-2Bα subunit cDNA encodes a 305 aa protein with 42% identity to yeast GCN3; it functionally complements a gcn3 deletion in yeast for GCN4-dependent gene induction, establishing GCN3 as the yeast ortholog of mammalian eIF-2Bα. cDNA cloning from rat brain library, in vitro expression, Northern blotting, functional complementation of gcn3-null yeast Proceedings of the National Academy of Sciences of the United States of America High 7753796
2015 VWM-associated mutations in eIF2Bα cause diverse biochemical defects including loss of binding to the eIF2B complex, reduction of GEF activity, or (unexpectedly) increased GEF activity, demonstrating that eIF2Bα participates in both structural integrity and regulatory modulation of the eIF2B complex. Overexpression of mutant eIF2Bα in HEK293 cells, affinity chromatography, co-immunoprecipitation of complex subunits, GEF activity assays BMC medical genetics Medium 26285592
2021 CRISPR-generated zebrafish eif2b3 loss-of-function mutants display defects in myelin development, glial cell differentiation, increased integrated stress response gene expression, and ectopic VEGF-driven angiogenesis; VEGF receptor inhibition reduces ectopic angiogenesis, providing a VWM disease model and validating 19 human EIF2B3 disease variants. CRISPR mutagenesis in zebrafish, histology/immunostaining of myelin and glia, gene expression analysis, in silico protein modeling, VEGF receptor inhibitor treatment (SU5416), validation of human variants Human molecular genetics High 33517449
2015 Oligodendrocytes transfected with mutant EIF2B3 (c.1037T>C) show decreased tolerance to ER stress, depressed autophagy flux (reduced Atg3 and Atg7 expression), and increased apoptosis; autophagy inducers restore viability, while autophagy inhibitors worsen apoptosis, placing EIF2B3 mutation in a pathway connecting ER stress to autophagic dysfunction. Oligodendrocyte transfection with EIF2B3 mutant vs. wild-type, cell viability and apoptosis assays, autophagy flux measurement, Atg gene expression analysis, autophagy modulator treatments Brain & development Medium 26625702
2015 ISRIB reverses ISR attenuation by targeting an interaction between eIF2 and eIF2B; clustered missense mutations at the amino-terminal portion of the eIF2Bδ subunit (introduced by CRISPR-Cas9) reverse both ISRIB-mediated ISR inhibition and its stimulatory effect on eIF2B GEF activity in vitro. Somatic mutation screen, CRISPR-Cas9 knock-in of mutations, eIF2B GEF activity assays in vitro, ISR reporter cell assays Science (New York, N.Y.) High 25858979
2018 Cryo-EM structure of human eIF2B at 4.1 Å resolution reveals ISRIB bound at the interface between the β and δ regulatory subunits; mutagenesis of residues lining this pocket alters ISRIB binding and the cellular ISR response, identifying a regulatory site that controls eIF2B activity. Cryo-electron microscopy (4.1 Å), site-directed mutagenesis of the ISRIB binding pocket, ISRIB binding assays in vitro, cellular ISR reporter assays Science (New York, N.Y.) High 29599245
2018 Atomic-resolution cryo-EM structure of human eIF2B shows it forms a decameric holoenzyme (two tetrameric subcomplexes); ISRIB binds in a deep central cleft and promotes assembly of the decamer by cross-bridging a central symmetry interface, thereby enhancing GEF activity. Cryo-electron microscopy (atomic resolution), biochemical reconstitution of decameric complex, ISRIB binding assays, assembly-state analysis Science (New York, N.Y.) High 29599213
2002 Mutations in EIF2B3 (encoding the γ subunit of eIF2B) cause leukoencephalopathy with vanishing white matter disease, demonstrating that all five eIF2B subunit genes can independently cause VWM. Mutation analysis/sequencing of EIF2B1-5 genes in VWM patients with previously unresolved genotype Annals of neurology Medium 11835386
2012 siRNA knockdown of eIF2Bγ in HCV-infected Huh7 cells inhibits HCV replication and core protein expression; combined knockdown of eIF2Bγ with IRES-specific siRNA produces stronger inhibition than either alone, confirming eIF2Bγ as an HCV co-factor in vivo. siRNA transfection in Huh7-HCV cells, fluorescence quantitative PCR, Western blotting for core protein Zhonghua gan zang bing za zhi Medium 23207339

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Generation and analysis of 280,000 human expressed sequence tags. Genome research 376 8889549
1993 Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor eIF-2B. The Biochemical journal 349 8397507
2019 Intrinsically Disordered Protein TEX264 Mediates ER-phagy. Molecular cell 296 31006538
2002 Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter. Annals of neurology 293 11835386
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2015 A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 198 26673895
2015 Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science (New York, N.Y.) 184 25858979
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2018 Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B. Science (New York, N.Y.) 161 29599245
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome research 151 11230166
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
2018 Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule. Science (New York, N.Y.) 147 29599213
2006 The DNA sequence and biological annotation of human chromosome 1. Nature 144 16710414
1992 Phosphorylation of eukaryotic initiation factor (eIF) 2 alpha and inhibition of eIF-2B in GH3 pituitary cells by perturbants of early protein processing that induce GRP78. The Journal of biological chemistry 116 1512215
1995 Modulation of tRNA(iMet), eIF-2, and eIF-2B expression shows that GCN4 translation is inversely coupled to the level of eIF-2.GTP.Met-tRNA(iMet) ternary complexes. Molecular and cellular biology 112 7565788
1994 The guanine nucleotide-exchange factor, eIF-2B. Biochimie 89 7893825
2000 Identification of eIF2Bgamma and eIF2gamma as cofactors of hepatitis C virus internal ribosome entry site-mediated translation using a functional genomics approach. Proceedings of the National Academy of Sciences of the United States of America 75 10900014
1996 Glucose stimulates the activity of the guanine nucleotide-exchange factor eIF-2B in isolated rat islets of Langerhans. The Journal of biological chemistry 73 8567668
1994 Purification and characterization of eukaryotic translational initiation factor eIF-2B from liver. Biochimica et biophysica acta 56 7803480
1994 Mutations in the GCD7 subunit of yeast guanine nucleotide exchange factor eIF-2B overcome the inhibitory effects of phosphorylated eIF-2 on translation initiation. Molecular and cellular biology 52 8164676
1994 Use of monoclonal antibodies to study the structure and function of eukaryotic protein synthesis initiation factor eIF-2B. European journal of biochemistry 48 8168527
1994 Expression of mutant eukaryotic initiation factor 2 alpha subunit (eIF-2 alpha) reduces inhibition of guanine nucleotide exchange activity of eIF-2B mediated by eIF-2 alpha phosphorylation. Molecular and cellular biology 41 8007958
2002 Evidence that the dephosphorylation of Ser(535) in the epsilon-subunit of eukaryotic initiation factor (eIF) 2B is insufficient for the activation of eIF2B by insulin. The Biochemical journal 40 12133000
1987 Evidence that phosphorylation of eIF-2(alpha) prevents the eIF-2B-mediated dissociation of eIF-2 X GDP from the 60 S subunit of complete initiation complexes. The Journal of biological chemistry 35 3646234
1988 Regulation of protein synthesis in rabbit reticulocyte lysate. Glucose 6-phosphate is required to maintain the activity of eukaryotic initiation factor (eIF)-2B by a mechanism that is independent of the phosphorylation of eIF-2 alpha. The Journal of biological chemistry 33 2842334
2012 Adult-onset vanishing white matter disease due to a novel EIF2B3 mutation. Archives of neurology 26 22312164
1984 The association of eIF-2 with Met-tRNAi or eIF-2B alters the specificity of eIF-2 phosphatase. The Journal of biological chemistry 25 6088496
2000 The activation of eukaryotic initiation factor (eIF)2B by growth factors in PC12 cells requires MEK/ERK signalling. FEBS letters 20 10913625
2012 A 66-year-old patient with vanishing white matter disease due to the p.Ala87Val EIF2B3 mutation. Neurology 18 23115207
1995 Purification and characterization of guanine nucleotide-exchange factor, eIF-2B, and p37 calmodulin-binding protein from calf brain. Journal of neurochemistry 17 7616232
1993 Preparation of a cell-free translation system with minimal loss of initiation factor eIF-2/eIF-2B activity. Analytical biochemistry 17 8368492
2012 Identification of intersubunit domain interactions within eukaryotic initiation factor (eIF) 2B, the nucleotide exchange factor for translation initiation. The Journal of biological chemistry 16 22238343
2015 Biochemical effects of mutations in the gene encoding the alpha subunit of eukaryotic initiation factor (eIF) 2B associated with Vanishing White Matter disease. BMC medical genetics 14 26285592
1991 The conversion of eIF-2.GDP to eIF-2.GTP by eIF-2B requires Met-tRNA(fMet). Biochemical and biophysical research communications 14 1764100
2021 Eif2b3 mutants recapitulate phenotypes of vanishing white matter disease and validate novel disease alleles in zebrafish. Human molecular genetics 13 33517449
1985 Evaluation and significance of kinetic parameters governing function of protein synthesis initiation factors eIF-2 and eIF-2B. FEBS letters 13 3844338
2015 Endoplasmic reticulum stress intolerance in EIF2B3 mutant oligodendrocytes is modulated by depressed autophagy. Brain & development 12 26625702
1987 Kinetic constants in the functioning of eIF-2 and eIF-2B. Biochemistry international 12 3435553
1995 Molecular cloning and characterization of cDNA encoding the alpha subunit of the rat protein synthesis initiation factor eIF-2B. Proceedings of the National Academy of Sciences of the United States of America 11 7753796
1994 Protein synthesis in the developing rat liver: participation of initiation factors eIF-2 and eIF-2B. Hepatology (Baltimore, Md.) 10 7802867
1984 Translation in micrococcal nuclease-treated cell-free extracts from Ehrlich ascites tumor cells. Stimulation by initiation factor eIF-2B. Biochimica et biophysica acta 9 6498200
2021 Identification of a Missense Variant in the EIF2B3 Gene Causing Vanishing White Matter Disease with Antenatal-Onset but Mild Symptoms and Long-Term Survival. Journal of molecular neuroscience : MN 8 33687620
1997 Catalysis of guanine nucleotide exchange on eIF-2 by eIF-2B: is it a sequential or substituted enzyme mechanism? Biochemical and biophysical research communications 8 9345299
1994 The delta-subunit of murine guanine nucleotide exchange factor eIF-2B. Characterization of cDNAs predicts isoforms differing at the amino-terminal end. The Journal of biological chemistry 8 7982969
2017 Postmortem Whole Exome Sequencing Identifies Novel EIF2B3 Mutation With Prenatal Phenotype in 2 Siblings. Journal of child neurology 7 28597716
2012 Identification of MRI1, encoding translation initiation factor eIF-2B subunit alpha/beta/delta-like protein, as a candidate locus for infantile epilepsy with severe cystic degeneration of the brain. Gene 7 23124037
1997 The effects of pyrroloquinoline quinone on heme-regulated eIF-2alpha kinase and eIF-2B activities in eukaryotic protein synthesis. Blood cells, molecules & diseases 7 9236156
2017 Case of Childhood Ataxia with Central Nervous System Hypomyelination with a Novel Mutation in EIF2B3 gene. Journal of pediatric neurosciences 6 28904586
1987 eIF-2B and the exchange of guanine nucleotides bound to eIF-2. The International journal of biochemistry 6 3647910
2021 A C-term truncated EIF2Bγ protein encoded by an intronically polyadenylated isoform introduces unfavorable EIF2Bγ-EIF2γ interactions. Proteins 4 34796993
2019 Correlation Between Vanishing White Matter Disease and Novel Heterozygous EIF2B3 Variants Using Next-Generation Sequencing: A Case Report. Annals of rehabilitation medicine 4 31072091
2024 Adult-onset leukoencephalopathy with vanishing white matter with compound heterozygous EIF2B3 gene variants. BMC neurology 3 38872124
1993 Purification of eukaryotic initiation factors eIF-2, eIF-2B and eIF-2 alpha kinase from bovine liver. Preparative biochemistry 3 8103216
2012 Childhood Ataxia with Cerebral Hypomyelination Syndrome: a Variant of Patient with Early Childhood Onset Related to EIF2B3 Mutation. A Case Report. The neuroradiology journal 2 24028880
2012 [siRNAs targeting La, hVAP-33, eIF2Bgamma, and HCV IRES inhibit the replication and expression of HCV in Huh7 cells]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 0 23207339
1994 Is there a need for channelling in the functioning of the protein synthesis initiation factors eIF-2 and eIF-2B? Biochemistry and molecular biology international 0 7866313