EIF2B4 source and evidence guide

This guide locates the evidence supporting the review. It is not an independent study. A cache marked abstract-only may have separately recovered original passages; a cache marked full-text may still contain an incomplete extraction. The scopes below state what was actually inspected. No supplement, figure pixels, atomic contact reanalysis or exact construct sequence is implied unless expressly described.

Sources and original access

PMID:11323413

Characterization of the mammalian initiation factor eIF2B complex as a GDP dissociation stimulator protein.. Selected full original Methods468–646,Results648–717/848–1040: native HeLa cytoplasmic whole-factor purification and exchange; recombinant alpha/beta experiments not transferred to delta.
Cache: publications/PMID_11323413.md; full_text_available: false; SHA256 ec823995789c31c53a1f798bf81023d5d4e493a969308461b1b15e80f3bc7337.

PMID:12499492

A severe variant of childhood ataxia with central hypomyelination/vanishing white matter leukoencephalopathy related to EIF21B5 mutation.. Authentic abstract only, severe EIF2B5 clinical phenotype. Exact delta heat-response support unresolved; no wrong-gene conclusion from incomplete access.
Cache: publications/PMID_12499492.md; full_text_available: false; SHA256 efcb1d43c86350b0b95d0fb684be641ebb1ca10b63b2d6af582256727d89b2fe.

PMID:12556349

Reduced amino acid availability inhibits muscle protein synthesis and decreases activity of initiation factor eIF2B.. Authentic complete abstract: normal swine amino-acid depletion/replacement, whole-muscle eIF2B exchange and protein synthesis. No human delta-specific nutrient sensor.
Cache: publications/PMID_12556349.md; full_text_available: false; SHA256 35c2ecd5cbc86277086448da490aecc82b5c32ea99b70d90b43edda2a603afd8.

PMID:14566705

eIF2B-related disorders: antenatal onset and involvement of multiple organs.. Selected primary indexed Methods/clinical Table1/Discussion: human delta patients 4–6 are distinct from beta/epsilon cases and MRI exemplars. Positive antenatal/multisystem phenotype; no cellular mechanistic assay.
Cache: publications/PMID_14566705.md; full_text_available: false; SHA256 6bd9ac2ef7155c6eb4f57e7490a187758325666c17f77da848671e626e0b536a.

PMID:15054402

Decreased guanine nucleotide exchange factor activity in eIF2B-mutated patients.. Selected primary Methods/Results/Table1/Discussion: human patient lymphoblast extracts, rat liver eIF2 substrate; actual delta genotypes and reduced whole-complex GDP exchange. No isolated-subunit assay.
Cache: publications/PMID_15054402.md; full_text_available: false; SHA256 25c3ade454409e484565cfd159428846636bc653117aa2a6a2e02c63d46be939.

PMID:15060152

Mutations linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways.. Selected original human cloning/Methods, assembly Results/Fig1 and mutant Results/Figure 4. Stable four/five-subunit complexes; negative/weak isolated pair combinations and endogenous bridging limits retained.
Cache: publications/PMID_15060152.md; full_text_available: true; SHA256 156d464d437c17d85a21181b9cb56c5a01f86eef50a76d9fa1a267f6de81b1dc.

PMID:15217090

The life and death of oligodendrocytes in vanishing white matter disease.. Selected original Methods, genotype Table1, oligodendrocyte Results and Discussion. Inspected patients are epsilon 1–4 and beta 5; delta-specific IMP developmental support unresolved.
Cache: publications/PMID_15217090.md; full_text_available: false; SHA256 2d08c635e04d508330ae04bbac0a2ff52a48f3b6b47a6b8204a82d8957da940d.

PMID:15507143

Screening for known mutations in EIF2B genes in a large panel of patients with premature ovarian failure.. Complete operative normal-cache Methods/Results/Discussion.93 isolated POF patients lack screened variants; paper contextualizes prior ovarioleukodystrophy, not a positive mutation experiment in this cohort.
Cache: publications/PMID_15507143.md; full_text_available: true; SHA256 fbe1a6164c493f2f8592828e21367e6dae6b5a4ccd50ff92117a0860c5fc0eab.

PMID:16289705

An efficient mammalian cell-free translation system supplemented with translation factors.. Authentic abstract: HeLa cell-free factor supplementation enhances translation. Complete Methods unavailable; independent human complex work corroborates established initiation role.
Cache: publications/PMID_16289705.md; full_text_available: false; SHA256 c62fe42768288a45221c04cf0fec987399e51cf494933d632429092a65121792.

PMID:25416956

A proteome-scale map of the human interactome network.. Authentic abstract and exact source-specific IntAct array/pooling/retest records. Normal flag true does not establish complete Methods access; no per-pair orthogonal validation claim.
Cache: publications/PMID_25416956.md; full_text_available: true; SHA256 884af86c50da9773efcb3ef4a5085a7b7b6bccc002e8fab180ad553ac591e671.

PMID:25858979

Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound.. The independently inspected source covers main Results/Figs1–3, CHO hamster delta mutants and whole-complex exchange; SI unavailable. No direct-binding claim is made from the 2015 assays.
Cache: publications/PMID_25858979.md; full_text_available: false; SHA256 48e7de1b46a1e59dea4d02c75879e4402e9d957cc202ddf87b844dbe91775dc1.

PMID:25910212

Widespread macromolecular interaction perturbations in human genetic disorders.. Authentic abstract and exact positive human pair/variant assay records. No complete original Methods or pair-specific orthogonal assay inspection.
Cache: publications/PMID_25910212.md; full_text_available: true; SHA256 25003121c44b0504fc6d0510bb8982bbc1efebe570515e1fcb696c685b0a54b6.

PMID:27023709

Expression, purification, and crystallization of Schizosaccharomyces pombe eIF2B.. Recovered original Methods/Results: S.pombe structural construction with explicitly distinct human whole-complex translation comparator. Host organism is not substituted for construct species.
Cache: publications/PMID_27023709.md; full_text_available: true; SHA256 24fbdc63dc56c647ba96c8d3cae410754631c826d7584d48c8456ded906aa52b.

PMID:28169297

Comparative influenza protein interactomes identify the role of plakophilin 2 in virus restriction.. Operative normal-cache Methods/Results and literal M2–delta co-IP records. Human host/EIF2B4 versus viral PR8 M2 distinguished; supplementary figure pixels not read.
Cache: publications/PMID_28169297.md; full_text_available: true; SHA256 68c3e84f504191b43268e2d6175cc55f3b4a6efedac63bfef27a7c744046d8a9.

PMID:29599213

Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.. Recovered original human reconstitution/structure main, captions and Methods PDF pages 2–4 and 7–10. Human beta/delta construction, delta L179V assembly gain and separate L179A experiments. No all-product equivalence or coordinate reanalysis.
Cache: publications/PMID_29599213.md; full_text_available: true; SHA256 8e41c97522808119bef1e4a699e5da88ae84997783a655d903fcb30f7f84fb22.

PMID:29599245

Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B.. Recovered BioC main passages0–13 and captions53–66: endogenous human HeLa eIF2B with ISRIB; distinct hamster mutant binding assays. Separate legitimate PMID, not a corrected identifier for29599213; SI not read.
Cache: publications/PMID_29599245.md; full_text_available: false; SHA256 14de0bc985cfcc0b5c1a6ee0acbdab78f9bac52a1df6f123a5dafb7833370f39.

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.. Original normal-cache Results paragraph 21 and Methods paragraphs 73–74/81: repeated variant interaction scoring and orthogonal subset. Exact target record joins separately; no universal orthogonal verification.
Cache: publications/PMID_31515488.md; full_text_available: true; SHA256 f6d30e80a705e6ac3ea3cacc1dde4c3e4bfaa83191fb66e3cfef377ebf6dd4f3.

PMID:32296183

A reference map of the human binary protein interactome.. Original cached Results paragraphs 16–17/Discussion paragraphs 43–45 plus literal target records. Pairwise quadruplicate retesting/sequence confirmation; cellular roles of individual associations remain separate.
Cache: publications/PMID_32296183.md; full_text_available: true; SHA256 de8eeaee8fd10c8537ad6b2f69602d414b6f1896221b208edb8ffbae9eaa263b.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.. Recovered DZNE primary PDF selected Methods and Results lines162–185/249–285/1460–1515; exact target records and reference sequences. ORFs or fragments, multiple yeast retests, orthogonal random subset not assumed for target.
Cache: publications/PMID_32814053.md; full_text_available: false; SHA256 df9eea608bd1079b9e3320715db0c16712ded397fd7cfde26b291d9ad54e6f3b.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.. Complete recovered original Methods paragraphs 211–227 and literal target records. Multiple-peptide/technical-replicate and background filters reduce false associations; no independent peptide-sequence audit or purified direct binding claim.
Cache: publications/PMID_33961781.md; full_text_available: true; SHA256 4763a1c8018e1b047fc1c2bf3d0e72c837e4b4c3dffbed428befa479e1c92286.

PMID:8626696

T-cell activation leads to rapid stimulation of translation initiation factor eIF2B and inactivation of glycogen synthase kinase-3.. Selected original Results/Discussion: stimulated primary human T cells and whole eIF2B exchange, beta abundance; full Experimental Procedures unavailable. No delta-specific proximal receptor mechanism.
Cache: publications/PMID_8626696.md; full_text_available: false; SHA256 396404cd79b61da5068d4b6e5c9e022a60d8d5d38c47a2dfa22214c4c6e1f5e7.

PMID:24532666

Analysis of the subunit organization of the eIF2B complex reveals new insights into its structure and regulation.. Authentic abstract only: mammalian subunit organization, delta tetramer assembly contribution, mouse tissue subunit abundance. No detailed original Methods claimed.
Cache: publications/PMID_24532666.md; full_text_available: false; SHA256 41ad1c75edc45b359c776cd69744fb8a609c2231cbb6830b284c89920ec62a64.

PMID:36943285

Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response.. Authentic complete review abstract: integrated stress response and whole-complex exchange context. Not an independent delta experiment.
Cache: publications/PMID_36943285.md; full_text_available: true; SHA256 e8132e5ca70c82bc78763495be9da51929e0206c257217198808e473fe2a56af.

PMID:37014850

eIF2Bδ blocks the integrated stress response and maintains eIF2B activity and cancer metastasis by overexpression in breast cancer stem cells.. Actual operative original Results paragraphs 31 and 40–49 and Methods paragraphs 63 and 75: human breast cancer cell contexts,543-aa Flag V1 overexpression, gradient/co-IP and extract GEF. Exact natural-product accession and free-delta/subcomplex mechanism remain unresolved.
Cache: publications/PMID_37014850.md; full_text_available: true; SHA256 e599eed0a74bb1a9ccb7d5d3fdee7bc51e441c48a2fc8cf2fb1475f2907561f3.

PMID:39139316

Ovarioleukodystrophy Due to EIF2B Genes: Systematic Review and Case Report.. Authentic complete systematic-review abstract: ovarian/white-matter clinical cases across EIF2B genes, enriched delta/epsilon. No independently inspected patient-level table or mechanism.
Cache: publications/PMID_39139316.md; full_text_available: true; SHA256 c6d037c4f6854fd32997886fb0502a024e497f9e614f2a434320dba49c52bd79.

PMID:39310746

eIF2B localization and its regulation during the integrated stress response is cell-type specific.. Actual human cell-line Results/Methods for endogenous delta immunolocalization with epsilon-mGFP bodies and stress-dependent redistribution. Co-localization does not resolve exact subcomplex stoichiometry.
Cache: publications/PMID_39310746.md; full_text_available: true; SHA256 6794c655f2d7e27779e3cd3cef24c5341e6b7954cd2d91cd3f5f90140102781e.

PMID:37981684

Genotypic and phenotypic heterogeneity among Chinese pediatric genetic white matter disorders.. Authentic complete clinical abstract includes human EIF2B4 splice variant and white-matter/cystic phenotype. Not a specific biochemical or developmental mechanism.
Cache: publications/PMID_37981684.md; full_text_available: true; SHA256 e7e83420c20da1784d0a3629a015d5b120e5864ee5e6386e941a83e039821c40.

PMID:31048492

Structural basis for eIF2B inhibition in integrated stress response.. The inspected evidence consists of abstract plus genuine RCSB 6K72 entity 4 and EMDB 9841,523-aa human delta G/H copies match canonical. Original Methods unavailable; no atomic contact reanalysis.
Cache: publications/PMID_31048492.md; full_text_available: false; SHA256 afbee8df7ae0688f4a14df19dde73521629405a230f0997e5c36f6380728d1d3.

PMID:9446619

Identification of interprotein interactions between the subunits of eukaryotic initiation factors eIF2 and eIF2B.. Selected indexed original Methods, Results and Figures 1–2: rat liver holoproteins and delta/epsilon far-Western binding, recombinant rat eIF2 subunits in Sf9. Direct publisher403 retained; not full-body or human assay.
Cache: publications/PMID_9446619.md; full_text_available: false; SHA256 74df0995189f9bdb99806905065bb3fb6a556dfd7606e4467e065e39f7926ec8.

PMID:9341116

Inactivation of eIF2B and phosphorylation of PHAS-I in heat-shocked rat hepatoma cells.. Authentic complete abstract: rat H35 heat-associated whole eIF2B activity. Complete donor original unavailable.
Cache: publications/PMID_9341116.md; full_text_available: false; SHA256 4bedb999860ab6aff71a95a5f89b3c7bd45f1c611a64d6f34432084ac707594c.

PMID:8567668

Glucose stimulates the activity of the guanine nucleotide-exchange factor eIF-2B in isolated rat islets of Langerhans.. Authentic complete abstract: glucose activates whole eIF2B in isolated rat islets, nonmetabolizable comparator negative; full Methods unavailable.
Cache: publications/PMID_8567668.md; full_text_available: false; SHA256 f1e63f45add5ce6dfd63eadec562b0e855d8a04db3542ab47e5fd03a6b626bbd.

PMID:8430778

Regulation of eukaryotic initiation factor-2B activity in muscle of diabetic rats.. Authentic complete abstract: diabetic rat muscle whole eIF2B/CKII/redox regulation. Exact hormone-treatment Methods unavailable; no delta-specific receptor mechanism.
Cache: publications/PMID_8430778.md; full_text_available: false; SHA256 db70d61bfaf724f85a3c21ac95a45e4889d4038509d8f7e5e0d629eb6d5225db.

Literal database and product checks

The analysis results, records.json and source-manifest.json preserve the exact IntAct assay/participant/feature fields, official reference sequences, family tree/MSA, ancestral IBD records, complete rat donor query, ARBA rules and human Reactome entity chain. The archive contains database records and source contexts, not recovered article bodies.

The canonical 523-aa sequence matches the PAINT target alignment and the deposited human 6K72 entity 4 sequence. That match does not establish functional equivalence of the other two natural products. VHL isoform 2 is independently reconstructed as a 172-aa product lacking canonical residues 114–154; the reference checksum is not proof of each experimental insert. Q53XC2 and reviewed beta P49770 have the same saved reference sequence.

Interpretation boundaries

Rat donor IDA support maps factor binding to PMID:9446619, heat response to PMID:9341116, glucose response to PMID:8567668 and peptide-hormone response to PMID:8430778. The first has selected original Methods/Results/captions; the other three remain abstract-only in this assessment. Their positive organismal context is retained without a human delta-specific sensor claim.

The PAINT target inherits three positive ancestral IBD terms on its recorded path. Donor number and the human target appearing among experimental sources are not defects. The path-level absence statement is restricted to the saved complete IBD snapshot.

PMID:15060152 supplies multicomponent assembly evidence, including negative isolated beta associations. PMID:29599213 independently supplies the human beta/delta interface. PMID:15507143 is a negative screen; the separate positive delta clinical/ovarian evidence comes from PMID:14566705.

The existing review retains 53 source objects while the current GOA has 49 contexts. Historical indices 2, 6, 7 and 13 are retained without lifecycle changes. The earlier raw file is preserved byte-exact in the dated snapshot.

2026-10-21 lifecycle and heat-response clarification

The earlier statement above about retaining historical absences without lifecycle changes is superseded by an explicit retirement decision. A complete fresh QuickGO query (49 hits, 49 results, one page) matches the 49 normal-current GOA contexts. Historical indices 2, 6, 7 and 13 remain in the review with retired flags; their scientific actions and original source identities remain intact. The dated 57-row GOA snapshot continues to locate the earlier assertions. This is source-snapshot provenance, not evidence that their biological functions are false.

For the heat-response annotation sourced to PMID:12499492, non-core retention is supported by the separately documented rat Q63186/PMID:9341116 IDA evidence already traced in the reproducible analysis. The two papers' access limits remain distinct: neither complete operative body was recovered in this assessment. Whole-factor heat regulation supports the conserved biological context without verifying the clinical paper's exact delta experiment or a direct human delta temperature-sensing mechanism. No cached availability flag, source identifier or inherited quotation changes.

Review follow-up: distinct evidence scopes

The PMID:32814053 FOS/KLKB1/LPL/GATM pairs have array, pooling and validated binary two-hybrid records. Their independently established partner classes remain recorded, but generic non-core binding is retained because the functional specificity of the proposed subtypes is unresolved for the actual tested molecules and no independent EIF2B4 role with these partners was established. The source permits full ORFs and fragments; reference sequences and blank feature fields do not prove exact inserts, mature processing states or natural-product equivalence. No target-specific orthogonal validation is asserted. By contrast, PMID:28169297 supplies positive M2 co-complex association by AP-MS and co-IP, including infected HEK293 cells, without resolving a direct M2–EIF2B4 contact; that generic association is retained without a transporter-binding replacement.

The clinical Table 1 and patient-6 description in PMID:14566705 support actual EIF2B4 multisystem disease and ovarian dysgenesis. PMID:15507143 supplies a negative isolated-POF known-variant screen and background discussion of earlier ovarian disease. Neither the clinical phenotype nor a proposed apoptosis explanation identifies a follicle-development step, and the electronic organ-development assignment likewise extends beyond the established translation mechanism. Their positive observations remain recorded while rows 9 and 36 are marked over-annotated; no definite citation defect is inferred. The same evidence boundary applies to the ARBA00026561 CNS-development inference in row 8, now also marked over-annotated. Both rules match the actual delta FunFam; their correct family conditions do not establish developmental participation beyond translation.

The donor references PMID:9341116, PMID:8567668 and PMID:8430778 are directly listed as reference-only support for rows 29/30, 33 and 34 respectively. Their abstract-only access and whole-factor assay limits remain as described above. Twenty-six individually inspected duplicate-title or mismatched-background excerpts are removed; 57 unchanged excerpts remain, including three informative titles supporting narrow findings. The unrelated support entries on rows 29/33/34 are removed while their top-level references and other uses remain. The original TAS citation on row 30 remains, with its source-access limitation. Reference-only evidence and original-source locators carry the supporting context without replacement quotations.