EIF2B1

Summary: The eIF2B complex containing alpha supports cytoplasmic translation initiation.

Reason: PMID:27023709 chiefly analyzes recombinant Schizosaccharomyces pombe eIF2B, but its Methods and Figure 2h also describe a human eIF2/eIF2B comparator in a reconstituted HCV-IRES translation assay. This supports participation of the human complex in cytoplasmic initiation. Alpha is a regulatory and structural subunit; the assay is not an isolated-alpha exchange measurement.

Summary: Alpha contributes to the initiation-factor activity of eIF2B.

Reason: The literal PAINT IBD for GO:0003743 is placed at PTN000028064, an ancestor of the exact human Q14232 leaf in the recovered family tree and alignment. Human Q14232 is the descendant experimental source for this IBD; self appearance is legitimate grounding, not circularity. The imported contributes_to qualifier correctly distinguishes subunit participation from autonomous activity.

Summary: EIF2B1 contributes to the activity of the translation initiation factor.

Reason: The authentic PMID:16289705 abstract reports enhancement of translation in HeLa extracts after supplementation with eIF2 and eIF2B. Its operative Methods were not recovered, so exact factor-preparation species and isoform are not independently assigned. The curator-supported contributes_to assertion agrees with independently read human complex reconstitution and is retained without claiming isolated-alpha activity.

Summary: The conserved alpha subunit contributes to nucleotide exchange by eIF2B.

Reason: The literal GO:0005085 IBD at PTN000028064 lies on the human target path and includes the stated PomBase, RGD, SGD and human descendant sources. The exact 305-aa target aligns to the official sequence. The conserved complex contribution is experimentally corroborated; neither donor count nor human self-grounding weakens this phylogenetic assertion. Preserve contributes_to.

Summary: Alpha enhances exchange activity as a component of eIF2B.

Reason: PMID:11323413 reports lower activity after removal of alpha and enhancement after recombinant-alpha addition, while identifying the epsilon subunit as catalytic. The complete operative body was not recovered, so unreported construct details remain unresolved. The positive contributes_to annotation is independently supported by the human alpha add-back and GDP-exchange experiments of PMID:29599213.

Summary: The annotated exchange activity is supported at the eIF2B-complex level.

Reason: The independently inspected PMID:25858979 main text and captions assay whole eIF2B nucleotide exchange and CHO Eif2b4 delta mutants. Supplementary Methods were unavailable. The supported activity is EIF2B1 contribution within the complex, independently corroborated by human alpha reconstitution in PMID:29599213. Preserve the imported enables value as source provenance, but do not treat its retention as validation of that relation: the source_defects entry requests a curator check of contributes_to. The integrated core retains contributes_to_molecular_function. No autonomous alpha exchange or negative isolated-alpha assay is inferred.

Summary: EIF2B1 participates in the exchange-factor machinery.

Reason: PMID:27023709 establishes the regulatory architecture mainly with S. pombe subunits and includes human complex-dependent translation in Figure 2h (Methods passage 12; Results passage 23). That endpoint is not a direct alpha-specific GDP-exchange assay. Direct human alpha reconstitution in PMID:29599213 supports the complex contribution. Retain the GEF action and imported enables value while recording a probable relation defect for upstream checking; the supported synthesis uses contributes_to, without claiming autonomous alpha catalysis or silently editing the source.

Summary: Positive binding to RD3 is retained as non-core.

Reason: The literal IntAct source join retains 3 positive human EIF2B1–RD3 record(s) from PMID:25416956, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HI-II-14 pairwise retesting and sequence confirmation. RD3 is a guanylyl-cyclase regulatory protein, not itself a guanylyl cyclase. No supported narrower binding class has been established for this pair. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair. The ClinGen project policy retains supported generic protein binding as non-core when no evidence-backed replacement is established.

Summary: Positive binding to NTAQ1 is retained with a specific partner class.

Reason: The literal IntAct source join retains 3 positive human EIF2B1–NTAQ1 record(s) from PMID:25416956, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HI-II-14 pairwise retesting and sequence confirmation. The official human NTAQ1 record assigns protein N-terminal glutamine amidohydrolase activity by similarity to mouse Q80WB5. This supports enzyme binding, without making EIF2B1 a hydrolase or identifying the binding surface. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair.

Proposed replacements: enzyme binding

Summary: Positive binding to GORASP2 is retained as non-core.

Reason: The literal IntAct source join retains 3 positive human EIF2B1–GORASP2 record(s) from PMID:25416956, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HI-II-14 pairwise retesting and sequence confirmation. GORASP2 is a Golgi stacking/tethering protein. Its PDZ domains do not by themselves establish that this interaction is mediated by a PDZ domain, so no narrower binding activity is assigned. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair. The ClinGen project policy retains supported generic protein binding as non-core when no evidence-backed replacement is established.

Summary: Positive binding to GORASP2 is retained as non-core.

Reason: The literal IntAct source join retains 1 positive human EIF2B1–GORASP2 record(s) from PMID:29892012, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used the wild-type versus mutant Y2H assay with autoactivation controls. The selected GORASP2 variant is recorded as having no effect on the interaction. GORASP2 domain content alone does not establish a domain-specific binding mechanism. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair. The ClinGen project policy retains supported generic protein binding as non-core when no evidence-backed replacement is established.

Summary: Positive binding to RD3 is retained as non-core.

Reason: The literal IntAct source join retains 1 positive human EIF2B1–RD3 record(s) from PMID:31515488, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used the replicated wild-type versus mutant Y2H assay with autoactivation controls. The curated RD3 variant is recorded as having no effect on the positive interaction. RD3 regulates enzymes but is not itself the guanylyl cyclase, and no narrower supported binding class was identified. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair. The ClinGen project policy retains supported generic protein binding as non-core when no evidence-backed replacement is established.

Summary: Positive binding to NTAQ1 is retained with a specific partner class.

Reason: The literal IntAct source join retains 1 positive human EIF2B1–NTAQ1 record(s) from PMID:31515488, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used the replicated wild-type versus mutant Y2H assay with autoactivation controls. The NTAQ1 variant is recorded as having no effect on binding. The official human NTAQ1 record assigns protein N-terminal glutamine amidohydrolase activity by similarity to mouse Q80WB5, supporting the enzyme-binding class without transferring catalysis to EIF2B1. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair.

Proposed replacements: enzyme binding

Summary: Positive binding to GORASP2 is retained as non-core.

Reason: The literal IntAct source join retains 1 positive human EIF2B1–GORASP2 record(s) from PMID:31515488, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used the replicated wild-type versus mutant Y2H assay with autoactivation controls. The selected GORASP2 variants are recorded as having no effect on binding. A protein with PDZ domains is not sufficient evidence for PDZ-domain binding without localization of this contact. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair. The ClinGen project policy retains supported generic protein binding as non-core when no evidence-backed replacement is established.

Summary: Positive binding to the UBE2I sequence Q7KZS0 is retained as non-core.

Reason: The literal IntAct source join retains 3 positive human EIF2B1–the UBE2I sequence Q7KZS0 record(s) from PMID:32296183, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HuRI pairwise verification by quadruplicate retesting and sequence confirmation. The selected unreviewed UBE2I sequence is 184 aa and shares the first 137 residues with the 158-aa canonical SUMO E2 P63279 before a divergent C terminus. Its curated reference checksum is exact, but enzyme function of this variant was not independently established. Preserve the positive pair without transferring canonical SUMO-conjugating activity or falsely calling it a ubiquitin E2. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair. The ClinGen project policy retains supported generic protein binding as non-core when no evidence-backed replacement is established.

Summary: Positive binding to RD3 is retained as non-core.

Reason: The literal IntAct source join retains 6 positive human EIF2B1–RD3 record(s) from PMID:32296183, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HuRI pairwise verification by quadruplicate retesting and sequence confirmation. RD3 is a regulatory partner, not the guanylyl cyclase whose activity it controls. No evidence-backed narrower binding subclass was established. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair. The ClinGen project policy retains supported generic protein binding as non-core when no evidence-backed replacement is established.

Summary: Positive binding to TRIM59 is retained with a specific partner class.

Reason: The literal IntAct source join retains 3 positive human EIF2B1–TRIM59 record(s) from PMID:32296183, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HuRI pairwise verification by quadruplicate retesting and sequence confirmation. The independent official TRIM59 record identifies experimentally supported ubiquitin E3 ligase activity. The binding class describes the partner; it does not imply that EIF2B1 is ubiquitinated, an E3 substrate, or a ligase. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair.

Proposed replacements: ubiquitin protein ligase binding

Summary: Positive binding to TRIML2 is retained as non-core.

Reason: The literal IntAct source join retains 3 positive human EIF2B1–TRIML2 record(s) from PMID:32296183, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HuRI pairwise verification by quadruplicate retesting and sequence confirmation. The selected official TRIML2 record does not establish catalytic E3 ligase activity. A TRIM-family name alone is insufficient for ligase-binding refinement. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair. The ClinGen project policy retains supported generic protein binding as non-core when no evidence-backed replacement is established.

Summary: Positive binding to NTAQ1 is retained with a specific partner class.

Reason: The literal IntAct source join retains 3 positive human EIF2B1–NTAQ1 record(s) from PMID:32296183, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HuRI pairwise verification by quadruplicate retesting and sequence confirmation. The official human NTAQ1 record assigns protein N-terminal glutamine amidohydrolase activity by similarity to mouse Q80WB5. Enzyme binding therefore provides a supported partner-class refinement without assigning a substrate relationship or catalytic effect to EIF2B1. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair.

Proposed replacements: enzyme binding

Summary: Positive binding to C1orf50 is retained as non-core.

Reason: The literal IntAct source join retains 3 positive human EIF2B1–C1orf50 record(s) from PMID:32296183, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HuRI pairwise verification by quadruplicate retesting and sequence confirmation. The selected official C1orf50 record provides no independently established catalytic or other informative partner class that warrants a narrower binding term. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair. The ClinGen project policy retains supported generic protein binding as non-core when no evidence-backed replacement is established.

Summary: Positive binding to GORASP2 is retained as non-core.

Reason: The literal IntAct source join retains 3 positive human EIF2B1–GORASP2 record(s) from PMID:32296183, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HuRI pairwise verification by quadruplicate retesting and sequence confirmation. The positive interaction does not identify the GORASP2 domain contacted. Golgi organization and PDZ-domain content are not transferred to EIF2B1 from this association. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair. The ClinGen project policy retains supported generic protein binding as non-core when no evidence-backed replacement is established.

Summary: Positive binding to MED29 is retained with a specific partner class.

Reason: The literal IntAct source join retains 3 positive human EIF2B1–MED29 record(s) from PMID:32296183, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HuRI pairwise verification by quadruplicate retesting and sequence confirmation. MED29 is an independently established Mediator transcription-coactivator subunit. This supports coactivator binding; it does not establish transcriptional coactivation by EIF2B1. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair.

Proposed replacements: transcription coactivator binding

Summary: Positive binding to ATF5 is retained with a specific partner class.

Reason: The literal IntAct source join retains 5 positive human EIF2B1–ATF5 record(s) from PMID:32296183, with participant taxon and sequence checksums kept separate from assay-host and fragment information. The study used HuRI pairwise verification by quadruplicate retesting and sequence confirmation. The independent official ATF5 record establishes sequence-specific DNA-binding transcription-factor activity. Its additional centrosomal role does not erase that class. The refinement states binding to that protein class, not EIF2B1 DNA binding or a demonstrated transcriptional outcome. These results do not establish the native cellular context or an independently verified orthogonal retest for this particular pair.

Proposed replacements: DNA-binding transcription factor binding

Summary: Human EIF2B1 binds the mouse alpha-2B adrenergic receptor tail.

Reason: PMID:9235896 used human EIF2B1 cDNA and murine adrenergic-receptor cytoplasmic tails in two-hybrid and GST pull-down experiments. Literal IntAct records identify mouse Adra2b P30545. The exact current binding-term definition supports alpha-2B receptor binding; neither human receptor testing nor receptor agonism is inferred. Historical construct numbering and engineered alternative starts are not equated to the natural 222-aa isoform.

Proposed replacements: alpha-2B adrenergic receptor binding

Summary: Human EIF2B1 binds the mouse alpha-2A adrenergic receptor tail.

Reason: The human EIF2B1/mouse Adra2a Q01338 pair is supported by literal two-hybrid and pull-down records from PMID:9235896 and the recovered original construct and assay descriptions. Alpha-2A receptor binding specifies this partner class. Binding to a cytoplasmic receptor tail is not evidence of extracellular ligand activity, agonism, or natural short-isoform function.

Proposed replacements: alpha-2A adrenergic receptor binding

Summary: Cytosol more precisely represents the established soluble complex pool.

Reason: The source annotation is positive for cytoplasm. Although the operative PMID:11323413 localization details were not recovered, the molecular role is independently resolved to cytosol by the exact human Reactome EIF2B1 entity and cytoplasmic imaging in PMID:9235896. Refine to cytosol while retaining the independently supported peripheral plasma-membrane annotation separately.

Proposed replacements: cytosol

Summary: The observed diffuse cytoplasmic pool is consistent with cytosol.

Reason: The recovered PMID:9235896 immunofluorescence Methods and Results describe transfected human HA-tagged EIF2B1 in 293 cells, distributed through the cytoplasm with exclusion from nuclei and an additional peripheral-membrane pool. The cytoplasmic assertion can be refined to cytosol, also explicitly assigned to the human EIF2B1 Reactome entity. This does not erase the distinct membrane pool or imply endogenous quantitative localization.

Proposed replacements: cytosol

Summary: Cytosol is the established site of the eIF2B complex.

Reason: The electronic assertion maps the official cytoplasmic location to cytosol. Independent target-specific Reactome entity 72517 has Q14232, human taxon, residues 1–305 and GO:0005829, and the human tagged-protein localization is compatible. This assertion does not require all EIF2B1 protein to be exclusively cytosolic.

Summary: The human EIF2B1 component is explicitly cytosolic in this reaction.

Reason: Reactome R-HSA-72670 contains input complex 72526, whose hasComponent edge leads to EIF2B1 entity 72517. That entity independently carries UniProt Q14232, human taxon, residues 1–305 and cytosol. Thus the localization is not merely copied from the reaction compartment.

Summary: The exchange reaction contains cytosolic human EIF2B1.

Reason: Reactome R-HSA-72722 catalyst activity 72528 points to eIF2B complex 72526, which contains target entity 72517; an independent input path runs through intermediate complex 72529. The target itself is assigned Q14232 and cytosol. The catalyst is the whole complex, not isolated alpha.

Summary: Conserved eIF2B complex membership is phylogenetically grounded.

Reason: The exact GO:0005851 IBD at PTN000028064 is an ancestor of the human target and cites the literal four descendant experimental sources. The matched 305-aa alignment and independent human subunit reconstitution support inherited complex membership. Human self-grounding is legitimate, and the number of donors is not a confidence penalty.

Summary: Alpha is a component of eIF2B.

Reason: PMID:11323413 positively reports alpha removal and re-addition to the mammalian exchange factor. Exact preparation details remain limited by unavailable operative full text, but the membership assertion is unambiguous and independently corroborated by human reconstitution in PMID:29599213.

Summary: Human alpha participates in the five-subunit complex.

Reason: Recovered PMID:15060152 cloning Methods identify human full-length cDNAs including EIF2B1 from HEK293 RNA, with sequence verification. The complex-formation Results and Figure 1 description include alpha in the assembled five-subunit complex. The focus on beta/epsilon disease mutations does not make the alpha membership assertion a misattribution.

Summary: The protein belongs to eIF2B, with species scope stated explicitly.

Reason: PMID:27023709 reconstructs the detailed structure chiefly using S. pombe subunits but also uses human eIF2B in the translation comparator. Human complex membership is independently established by the reconstitution in PMID:29599213 and the exact canonical human alpha chains in PDB 6K72. No equivalence of the 222-aa alternative product is assumed.

Summary: The automated complex-membership inference is supported.

Reason: The ARBA-sourced complex term agrees with independently read human subunit reconstitution, explicit Reactome target membership and the conserved PAINT placement. This is membership in a heteromeric exchange-factor complex, not a claim that alpha supplies its catalytic center.

Summary: Human alpha is directly incorporated into reconstructed eIF2B.

Reason: PMID:29599213 describes codon-optimized human subunit expression in E. coli, purified alpha homodimer and reconstitution with the beta/gamma/delta/epsilon tetramer. The assembled decamer has enhanced GDP exchange. Exact synthetic insert sequences in supplementary material were not independently authenticated, so no natural alternative-isoform equivalence is asserted.

Summary: A peripheral plasma-membrane pool was observed in the reported expression assay.

Reason: PMID:9235896 reports human HA-tagged EIF2B1 at the periphery of transfected 293 cells, with additional diffuse cytoplasmic localization. The paper reports receptor co-immunoprecipitation and tail binding, but these do not establish that all peripheral signal is receptor-bound. Retain the positive location as a contextual pool distinct from the principal cytosolic exchange-factor role; do not convert expression imaging into a quantified native distribution.

Summary: Cytoplasmic translation initiation gives the relevant process context.

Reason: The literal PAINT GO:0006413 IBD lies on the target path and is supported by the stated PomBase, rat and human descendant sources. No node-placement error is alleged. The human reconstituted translation experiment in PMID:27023709 and direct human subunit reconstitution in PMID:29599213 support the more specific cytoplasmic process. This is a refinement of an existing assertion, not an additional process proposed from disease necessity.

Proposed replacements: cytoplasmic translational initiation

Summary: Cytoplasmic translation initiation gives the relevant process context.

Reason: PMID:16289705 reports eIF2/eIF2B-dependent translation in HeLa extracts; the original factor-preparation Methods remain unavailable. The human reconstituted translation experiment in PMID:27023709 and direct human subunit reconstitution in PMID:29599213 support the more specific cytoplasmic process. This is a refinement of an existing assertion, not an additional process proposed from disease necessity.

Proposed replacements: cytoplasmic translational initiation

Summary: Cytoplasmic translation initiation gives the relevant process context.

Reason: The electronic ARBA initiation assertion agrees with the established eIF2B complex function. The human reconstituted translation experiment in PMID:27023709 and direct human subunit reconstitution in PMID:29599213 support the more specific cytoplasmic process. This is a refinement of an existing assertion, not an additional process proposed from disease necessity.

Proposed replacements: cytoplasmic translational initiation

Summary: The conserved complex participates in the translational heat response.

Reason: The literal ISS donor is rat Eif2b1 Q64270; its current experimental heat-response annotation cites PMID:9341116. The authentic donor abstract reports heat-dependent changes in eIF2B activity correlated with translation in rat hepatoma cells. Retain the curated conserved response as a context of complex function, not as an alpha-specific temperature sensor. Operative donor Methods were not recovered; the evidence does not establish a human heat assay or isolated-alpha regulation.

Summary: The specific heat-response support in this clinical citation remains unresolved.

Reason: PMID:12499492 is an authentic severe VWM clinical report whose abstract identifies an EIF2B5 mutation and altered metabolites. Full operative text could not be recovered. This does not prove that EIF2B1 is misattributed, but it does not independently resolve the source-specific human heat-response assertion. Preserve the source while leaving it undecided; the distinct rat-ortholog heat-response row is assessed separately.

Summary: Glucose-responsive translation is retained as a conserved complex context.

Reason: The actual ISS donor Q64270 has an experimental glucose-response annotation from PMID:8567668. Its authentic abstract reports glucose-dependent activation of eIF2B in isolated rat islets. The preserved inference concerns a conserved subunit in the regulated exchange-factor machinery, not autonomous glucose sensing by EIF2B1. Exact donor Methods and alpha-specific perturbations were not recovered, and a direct human glucose assay is not claimed.

Summary: EIF2B1-specific support for oligodendrocyte development is unresolved.

Reason: Recovered PMID:15217090 Methods, Results and Discussion examine oligodendrocyte density, differentiation markers, proliferation and apoptosis in VWM autopsy tissue; the identified patients carry EIF2B5 or EIF2B2 genotypes. These data support shared-complex disease relevance but do not independently resolve the imported EIF2B1-specific developmental assertion. Genotype focus alone is not evidence of curator misattribution. Preserve the positive source and use UNDECIDED rather than deny oligodendrocyte biology.

Summary: Plasma membrane specifies the observed peripheral membrane pool.

Reason: The recovered PMID:9235896 imaging Results identify a peripheral plasma-membrane pool of transfected human EIF2B1 in 293 cells as well as cytoplasmic signal. Refine the broad membrane term to that demonstrated compartment, preserving the source and acknowledging the expression-system scope. This is not an inference from membrane topology or a claim that EIF2B1 is an integral membrane protein.

Proposed replacements: plasma membrane

Summary: Alpha self-association is part of the functional eIF2B architecture.

Reason: The literal HI-II-14 record is a positive human self pair, within the study's retesting and sequence-confirmation framework. The alpha homodimer is independently established by PMID:29599213 and contributes to decamer assembly. This supports identical-protein binding as a core-relevant interaction, without making every engineered variant or the 222-aa alternative product functionally equivalent.

Summary: Alpha self-association is part of the functional eIF2B architecture.

Reason: The literal Y2H record preserves both the positive wild-type self pair and its disruptive/no-effect variant features; the paper requires strong wild-type interactions and replicated mutant comparisons. The alpha homodimer is independently established by PMID:29599213 and contributes to decamer assembly. This supports identical-protein binding as a core-relevant interaction, without making every engineered variant or the 222-aa alternative product functionally equivalent.

Summary: Alpha self-association is part of the functional eIF2B architecture.

Reason: Purified human alpha forms a homodimer in the operative reconstitution, analytical ultracentrifugation and structural experiments. This homodimer contributes to decamer assembly. This supports identical-protein binding as a core-relevant interaction, without making every engineered variant or the 222-aa alternative product functionally equivalent.

Summary: Alpha self-association is part of the functional eIF2B architecture.

Reason: The positive wild-type Y2H self interaction is retained separately from the listed disruptive and non-disruptive variants; replicated mutant comparisons are not evidence that wild-type self binding is absent. The alpha homodimer is independently established by PMID:29599213 and contributes to decamer assembly. This supports identical-protein binding as a core-relevant interaction, without making every engineered variant or the 222-aa alternative product functionally equivalent.

Summary: Alpha self-association is part of the functional eIF2B architecture.

Reason: The HuRI self pair has positive array, pooling and validated two-hybrid records; the original study uses pairwise retesting and sequence confirmation. The alpha homodimer is independently established by PMID:29599213 and contributes to decamer assembly. This supports identical-protein binding as a core-relevant interaction, without making every engineered variant or the 222-aa alternative product functionally equivalent.

Summary: Peptide-hormone response is retained as a conserved translation-regulation context.

Reason: The actual rat Q64270 donor carries an experimental GO:0043434 assertion from PMID:8430778. Its authentic abstract reports tissue-dependent changes in eIF2B activity in diabetic rats and biochemical regulation of partially purified factor. Preserve the curated ortholog inference as a contextual response of the complex; it does not establish EIF2B1 as a peptide-hormone receptor or identify an alpha-specific signaling mechanism. Full operative donor Methods remain unavailable.

Summary: Alpha promotes the exchange-factor step supporting initiation.

Reason: The human alpha homodimer add-back experiments in PMID:29599213 enhance activity of the reconstructed beta/gamma/delta/epsilon complex and assemble the decamer. This supplies a structural contribution to the nucleotide-exchange step that enables initiation, rather than a claim based solely on knockout necessity. Alpha-free complexes retain measurable activity and can be activated by ISRIB, so alpha is not described as absolutely indispensable under every assay condition.

Summary: The source-specific T-cell receptor signaling assignment remains unresolved.

Reason: Recovered PMID:8626696 Results and Discussion measure eIF2B activity and beta-subunit abundance during activation of primary human T cells with ionomycin/PMA; phytohemagglutinin effects are also reported. These findings establish regulated translation during T-cell activation, but the recovered scope does not resolve EIF2B1-specific participation in the receptor-initiated signaling process defined by GO:0050852. Complete operative Methods were not recovered. Preserve the IDA source and do not infer a false annotation merely because another subunit was foregrounded.