Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003743 translation initiation factor activity	IBA GO_REF:0000033	ACCEPT	Summary: eIF2α is the catalytic subunit of the eIF2 GTPase complex that delivers initiator tRNA to the ribosome. This molecular function term accurately captures its primary role in translation initiation. IBA evidence through phylogenetic comparison is appropriate. Reason: eIF2α is fundamentally a translation initiation factor with GTPase activity. Its core function is delivering formyl-Met-tRNAi to the 40S ribosome as part of the ternary complex. This is more specific and informative than generic protein binding terms and represents a core function of the protein. Supporting Evidence: PMID:14698289 Eukaryotic translation initiation factor 2 (eIF2) is a G-protein that functions as a central switch in the initiation of protein synthesis. In its GTP-bound state it delivers the methionyl initiator tRNA (Met-tRNA(i)) to the small ribosomal subunit PMID:2649894 These data further suggest that eIF-2 is an important component of the preinitiation complex that mediates ribosomal recognition of a start codon during the scanning process
GO:0006413 translational initiation	IBA GO_REF:0000033	ACCEPT	Summary: eIF2α is absolutely required for the initiation phase of translation, functioning as the central GTPase that coordinates ternary complex delivery and start codon recognition. This biological process annotation is appropriate and represents a core function. Reason: eIF2α is essential for translation initiation as it is the catalytic component of the eIF2 complex responsible for the GTP-dependent delivery of initiator tRNA to the 40S ribosome. This is not merely associated with but mechanistically essential for initiation. IBA evidence is appropriate. Supporting Evidence: PMID:14698289 In its GTP-bound state it delivers the methionyl initiator tRNA (Met-tRNA(i)) to the small ribosomal subunit and releases it upon GTP hydrolysis following the recognition of the initiation codon
GO:0005850 eukaryotic translation initiation factor 2 complex	IBA GO_REF:0000033	ACCEPT	Summary: SUI2/eIF2α is the alpha subunit of the eIF2 heterotrimeric complex. This is a core structural component annotation that is mechanistically accurate. IBA evidence through phylogenetic comparison is appropriate. Reason: eIF2α is by definition a subunit of the eIF2 complex. This is not a function but a structural component annotation, which is distinct from catalytic activity. SUI2 is the founding member of this complex. This represents core cellular machinery that defines the protein. Supporting Evidence: PMID:2649894 the sui2 suppressor gene encodes the alpha subunit of eIF-2
GO:0033290 eukaryotic 48S preinitiation complex	IBA GO_REF:0000033	ACCEPT	Summary: eIF2α is a component of the 48S preinitiation complex, delivering the initiator tRNA that is required for complex assembly and function. This annotation reflects the core mechanism of translation initiation. Reason: eIF2α is an essential component of the 48S preinitiation complex, which forms when the eIF2-GTP-Met-tRNAi ternary complex binds to the 40S ribosomal subunit followed by mRNA binding. The 48S complex is the functional intermediate in initiation. This is a core annotation. Supporting Evidence: PMID:14698289 In its GTP-bound state it delivers the methionyl initiator tRNA (Met-tRNA(i)) to the small ribosomal subunit and releases it upon GTP hydrolysis following the recognition of the initiation codon
GO:0043022 ribosome binding	IBA GO_REF:0000033	MODIFY	Summary: eIF2α delivers initiator tRNA to the 40S ribosomal subunit as part of the ternary complex, but the molecular function is better described as translation initiation factor activity which is more specific. Ribosome binding is present but is a consequence of its role in ternary complex delivery. Reason: Ribosome binding is overly generic and does not capture the specific mechanism by which eIF2α interacts with ribosomes. eIF2α does not directly bind the ribosome in isolation - it delivers initiator tRNA to the 40S ribosomal subunit as a GTP-dependent, ternary complex-mediated interaction. A more mechanistically accurate term would be formyl-Met-tRNA delivery or the existing translation initiation factor activity (GO:0003743) which is already annotated and more specific. The generic ribosome binding conflates this with other ribosomal interactions that may occur through different mechanisms. Proposed replacements: translation initiation factor activity methionyl-initiator methionine tRNA binding
GO:0003676 nucleic acid binding	IEA GO_REF:0000002	REMOVE	Summary: eIF2α contains RNA-binding domains but does not directly bind nucleic acid. The binding interaction is mediated entirely through the methionyl-tRNA substrate. This IEA annotation appears to be a computational inference from InterPro domains that are present but functionally contribute to tRNA binding, not nucleic acid binding per se. Reason: eIF2α does not function as a nucleic acid-binding protein in the traditional sense. The RNA-binding domains identified by InterPro are structural components that facilitate methionyl-tRNA recognition, not general nucleic acid binding. eIF2α specifically recognizes and binds the methionyl-tRNA through protein-RNA interactions, but this is better captured by the term "methionyl-initiator methionine tRNA binding" (GO:1990856), not the generic nucleic acid binding. Including this term conflates structural domains with functional role and is misleading about eIF2α's mechanism of action.
GO:0003723 RNA binding	IEA GO_REF:0000120	REMOVE	Summary: eIF2α binds methionyl-initiator tRNA through specific protein-RNA interactions, but generic RNA binding is overly broad and misleading. The binding is strictly limited to formyl-Met-tRNAi and involves specific recognition of the methionine moiety and acceptor stem identity elements. Reason: While eIF2α does interact with RNA (methionyl-tRNA), the term "RNA binding" is problematic because it suggests broad RNA-binding capability or nonspecific RNA interactions. eIF2α specifically recognizes only the initiator methionyl-tRNA through GTP-dependent binding that is disrupted upon GTP hydrolysis. This specific tRNA-recognition function is far better represented by the existing annotation "methionyl-initiator methionine tRNA binding" (GO:1990856). Generic "RNA binding" inappropriately groups this with proteins that have different binding specificity and mechanisms.
GO:0003743 translation initiation factor activity	IEA GO_REF:0000120	ACCEPT	Summary: This is a duplicate of the IBA annotation for the same term (GO:0003743). Both annotations describe eIF2α's translation initiation factor activity. The IBA annotation has higher evidence quality from experimental validation and phylogenetic comparison. Reason: While this is a duplicate with lower evidence quality (IEA vs IBA), having multiple evidence types for the same annotation strengthens the overall evidence base. The IEA annotation validates the computational inference supports the experimental evidence. Retaining both provides evidence aggregation. The IBA annotation is the primary evidence; this complements it. Supporting Evidence: PMID:14698289 Eukaryotic translation initiation factor 2 (eIF2) is a G-protein that functions as a central switch in the initiation of protein synthesis
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: eIF2α is localized to the cytosol where it functions in translation initiation. This IEA annotation from UniProtKB subcellular location mapping is accurate and represents core localization information. Reason: eIF2α is a cytosolic protein, as confirmed by both experimental subcellular localization studies and its function in cytosolic translation initiation. This is appropriate background/context for the protein function. The annotation is accurate and complementary to functional annotations.
GO:0006412 translation	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: eIF2α is essential for the initiation phase of translation, but broader annotation to "translation" is overly general. The more specific term "translational initiation" (GO:0006413) is already annotated and more accurately represents eIF2α's role. Reason: While eIF2α is indeed involved in translation, it is specifically involved in the initiation phase. The broader term "translation" includes elongation and termination phases in which eIF2α does not directly participate. The specific "translational initiation" term (GO:0006413) is more accurate and is already annotated. This broader term can be retained as non-core context but should not be treated as a primary function annotation.
GO:0006413 translational initiation	IEA GO_REF:0000043	ACCEPT	Summary: This is a duplicate of the IBA annotation for translational initiation (line 2). eIF2α is mechanistically essential for translation initiation. Multiple evidence types strengthen the annotation. Reason: This IEA annotation duplicates the IBA evidence already provided. Multiple evidence types for the same accurate annotation strengthen confidence. IEA based on keyword mapping complements IBA experimental evidence. Both are retained.
GO:0005515 protein binding	IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy...	MARK AS OVER ANNOTATED	Summary: Generic protein binding annotation from mass spectrometry-based proteome survey. eIF2α is a subunit of the eIF2 complex that directly interacts with the beta (SUI3) and gamma (GCD1/GCD2) subunits, but the term "protein binding" is uninformative. Reason: eIF2α is a structural component of the eIF2 heterotrimeric complex. While it does bind to the beta and gamma subunits, annotating this as generic "protein binding" provides no functional insight. The specific subunit interactions and complex membership are better captured by the "eukaryotic translation initiation factor 2 complex" (GO:0005850) annotation. Generic protein binding annotations should be avoided per GO curation guidelines as they are uninformative. The relevant mechanistic details are conveyed through the complex membership annotation. Supporting Evidence: PMID:11805837 Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.
GO:0005515 protein binding	IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine...	MARK AS OVER ANNOTATED	Summary: Protein binding from large-scale proteome survey. Similar to above, eIF2α interactions are better described through complex membership and specific functional terms. Reason: Generic protein binding is uninformative and should not be used when more specific terms are available. The eIF2 complex membership annotation (GO:0005850) and specific interactions with GCD1 and CDC123 are more informative. Supporting Evidence: PMID:16429126 Proteome survey reveals modularity of the yeast cell machinery.
GO:0005515 protein binding	IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom...	MARK AS OVER ANNOTATED	Summary: Protein binding from global landscape of yeast protein complexes study. Again, uninformative generic term for eIF2 complex membership. Reason: Generic protein binding term. Specific mechanistic descriptions through complex annotations are preferred. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
GO:0005515 protein binding	IPI PMID:18719252 High-quality binary protein interaction map of the yeast int...	MARK AS OVER ANNOTATED	Summary: Protein binding from high-quality binary protein interaction map. Generic annotation. Reason: Generic protein binding term should be replaced with mechanistically informative annotations describing the eIF2 complex. Supporting Evidence: PMID:18719252 High-quality binary protein interaction map of the yeast interactome network.
GO:0005515 protein binding	IPI PMID:20485439 eIF5 has GDI activity necessary for translational control by...	MARK AS OVER ANNOTATED	Summary: eIF5-SUI2 interaction relevant to translational control by eIF2 phosphorylation. While eIF5 (TIF5) does interact with eIF2α in the multifactor complex, generic protein binding is uninformative. Reason: The eIF5 interaction is important for translational control, but this is better captured through more specific functional annotations of the multifactor complex and stress response mechanisms. Supporting Evidence: PMID:20485439 eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation.
GO:0005515 protein binding	IPI PMID:24852487 eIF2B is a decameric guanine nucleotide exchange factor with...	MARK AS OVER ANNOTATED	Summary: eIF2B interaction study. eIF2B (the GEF) physically interacts with eIF2α to catalyze GDP/GTP exchange, but generic protein binding obscures this mechanistic detail. Reason: The eIF2B-eIF2α interaction is mechanistically important for nucleotide exchange and stress response, but generic "protein binding" does not convey this. More specific functional terms would be appropriate. Supporting Evidence: PMID:24852487 eIF2B is a decameric guanine nucleotide exchange factor with a
GO:0005515 protein binding	IPI PMID:26211610 Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is ...	MARK AS OVER ANNOTATED	Summary: Cdc123 interaction study. CDC123 is an assembly factor for eIF2. This specific interaction is mechanistically important but generic protein binding does not capture it. Reason: CDC123 facilitates eIF2α assembly as part of complex biogenesis, but generic protein binding fails to capture this functional role. Better described through complex assembly and protein folding assistance terms. Supporting Evidence: PMID:26211610 Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein with Unique Features.
GO:0005515 protein binding	IPI PMID:27107014 An inter-species protein-protein interaction network across ...	MARK AS OVER ANNOTATED	Summary: Inter-species protein interaction network. Generic protein binding from computational/comparative analysis. Reason: Generic protein binding annotation. More specific mechanistic descriptions are available. Supporting Evidence: PMID:27107014 An inter-species protein-protein interaction network across vast evolutionary distance.
GO:0005515 protein binding	IPI PMID:37507029 Binding of human Cdc123 to eIF2γ.	MARK AS OVER ANNOTATED	Summary: Human CDC123 binding to human eIF2γ (orthologous to yeast). While the orthology is relevant, generic protein binding is not informative for mechanistic understanding. Reason: Generic protein binding. The specific role in assembly and protein folding assistance would be more informative. Supporting Evidence: PMID:37507029 Binding of human Cdc123 to eIF2
GO:0005515 protein binding	IPI PMID:37968396 The social and structural architecture of the yeast protein ...	MARK AS OVER ANNOTATED	Summary: Social and structural architecture of yeast protein interactome. Generic proteome-wide interaction annotation. Reason: Generic protein binding from large-scale network study. Specific mechanistic interactions should be described through more informative terms. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome.
GO:0005515 protein binding	IPI PMID:8947054 Ligand interactions with eukaryotic translation initiation f...	MARK AS OVER ANNOTATED	Summary: Early study of eIF2 gamma subunit interactions with ligands and partner proteins. While this paper describes mechanistic eIF2 interactions, the generic "protein binding" term fails to capture the functional insights. Reason: This foundational paper likely describes the heterotrimer assembly, but generic protein binding is uninformative. The specific complex assembly and function should be captured through "eukaryotic translation initiation factor 2 complex" (GO:0005850) and related functional terms. Supporting Evidence: PMID:8947054 Ligand interactions with eukaryotic translation initiation factor 2: role of the gamma-subunit.
GO:0003743 translation initiation factor activity	IDA PMID:16565414 Yeast initiator tRNA identity elements cooperate to influenc...	ACCEPT	Summary: Direct experimental evidence demonstrating eIF2α's translation initiation factor activity using a reconstituted yeast translation system. This IDA annotation has higher evidence quality than IBA and IEA versions of the same term. Reason: This is experimental evidence (IDA) for eIF2α's core molecular function. The reconstituted translation system study directly demonstrates how initiator tRNA identity elements influence eIF2α binding and interaction with the ternary complex. This is the highest quality evidence for the functional role. Multiple evidence codes for the same term strengthen confidence. Supporting Evidence: PMID:16565414 the initiator-specific A1:U72 base pair at the top of the acceptor stem is important for the binding of the eIF2.GTP.Met-tRNA(i) ternary complex to the 40S ribosomal subunit
GO:0005840 ribosome	IDA PMID:12008673 Development and characterization of a reconstituted yeast tr...	ACCEPT	Summary: eIF2α is demonstrated to interact with ribosomes in a reconstituted translation initiation system. However, this is more specifically part of the 48S preinitiation complex (already annotated) and formation of the preinitiation complex. Reason: eIF2α is shown experimentally to associate with ribosomes as part of the initiation process. While "ribosome" is a broad cellular_component term, it accurately describes the subcellular localization/association of eIF2α when functioning in translation initiation. The more specific 48S preinitiation complex annotation provides mechanistic detail. Retaining both gives context about cellular location of function. Supporting Evidence: PMID:12008673 Development and characterization of a reconstituted yeast translation initiation system
GO:0006413 translational initiation	IDA PMID:8947054 Ligand interactions with eukaryotic translation initiation f...	ACCEPT	Summary: This is a duplicate of the IBA and IEA annotations for translational initiation. Direct experimental evidence from mechanistic studies of eIF2 gamma subunit ligand interactions provides strong support. Reason: Multiple evidence types (IBA, IEA, IDA) for the same mechanistically critical annotation strengthen confidence. The IDA evidence provides direct experimental support from biochemical studies of eIF2 complex function. Supporting Evidence: PMID:8947054 Ligand interactions with eukaryotic translation initiation factor 2: role of the gamma-subunit.
GO:0005850 eukaryotic translation initiation factor 2 complex	IPI PMID:23775072 Translation initiation requires cell division cycle 123 (Cdc...	ACCEPT	Summary: Experimental identification of eIF2 complex membership through CDC123 interaction study. This provides direct biochemical evidence of SUI2 as a component of the eIF2 complex and its interaction with CDC123, an assembly factor. Reason: Direct experimental evidence (IPI) showing SUI2 interaction with GCD1 (gamma subunit) and with CDC123, confirming eIF2 complex assembly. This complements the IBA and IMP annotations with biochemical evidence of complex formation and cofactor interactions. This is core annotation. Supporting Evidence: PMID:23775072 Translation initiation requires cell division cycle 123 (Cdc123) to facilitate biogenesis of the eukaryotic initiation factor 2 (eIF2)
GO:0010494 cytoplasmic stress granule	HDA PMID:26777405 ATPase-Modulated Stress Granules Contain a Diverse Proteome ...	KEEP AS NON CORE	Summary: eIF2α is a component of cytoplasmic stress granules, which form when translation is attenuated during stress. The evidence from HDA (homology-derived annotation) suggests stress granule localization may be conserved. However, more mechanistically, eIF2α is involved in translational control OF stress responses, not localization to stress granules itself. Reason: eIF2α is phosphorylated during stress and this phosphorylation triggers translational attenuation and GCN4 upregulation. The association with stress granules is a secondary consequence of translational shutdown, not a primary function. The core function is "translation control in response to stress" rather than stress granule localization. This annotation can be retained as contextual but is not a core function of the protein. HDA evidence quality is lower than IDA/IBA. Supporting Evidence: PMID:26777405 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure.
GO:1990856 methionyl-initiator methionine tRNA binding	IDA PMID:16565414 Yeast initiator tRNA identity elements cooperate to influenc...	ACCEPT	Summary: Direct experimental evidence demonstrating eIF2α's specific binding to methionyl-initiator tRNA using a reconstituted yeast translation system. This is eIF2α's most direct and specific molecular interaction, critical for ternary complex formation and initiation. Reason: This is eIF2α's core ligand-binding function. The methionyl-initiator tRNA is the only substrate that eIF2α efficiently binds in the GTP-bound state. This represents the fundamental molecular interaction that underlies eIF2α's role as a translation initiation factor. The paper demonstrates that initiator-specific tRNA identity elements are recognized by eIF2α. This is not just a binding activity but THE defining molecular interaction of the protein. Supporting Evidence: PMID:16565414 the initiator-specific A1:U72 base pair at the top of the acceptor stem is important for the binding of the eIF2.GTP.Met-tRNA(i) ternary complex to the 40S ribosomal subunit
GO:0005525 GTP binding	IDA PMID:14698289 GTP-dependent recognition of the methionine moiety on initia...	ACCEPT	Summary: Direct experimental evidence from thermodynamic characterization of eIF2 shows GTP-dependent binding interactions with methionyl-tRNA. GTP binding is the nucleotide-binding function but represents a mechanism for methionyl-tRNA recognition rather than a general GTPase activity. The relation between GTP binding and methionine moiety recognition is mechanistically key. Reason: eIF2α is a GTPase that binds GTP and hydrolyzes it during the translation initiation cycle. The GTP binding is mechanistically important because GTP binding creates a conformational state that specifically recognizes the methionine moiety on initiator tRNA. This is not generic GTP binding but GTP-regulated methionyl-tRNA recognition. The term "GTP binding" is appropriate for this molecular interaction. Supporting Evidence: PMID:14698289 In its GTP-bound state the factor forms a positive interaction with the methionine moiety on Met-tRNA(i) that is disrupted when GTP is replaced with GDP
GO:0005525 GTP binding	IDA PMID:16246727 Pi release from eIF2, not GTP hydrolysis, is the step contro...	ACCEPT	Summary: This is a duplicate GTP binding annotation from another mechanistic study demonstrating that phosphate (Pi) release from eIF2, not GTP hydrolysis itself, is the step controlled during start site selection. This provides complementary evidence that GTP binding/hydrolysis is central to the initiation mechanism. Reason: Multiple IDA annotations of GTP binding from different mechanistic studies strengthen evidence. The second paper provides additional insight that Pi release (GTPase product release) rather than GTP hydrolysis per se is the rate-limiting step for start codon recognition. Both papers confirm GTP binding and GTPase activity are mechanistically central to eIF2α function. Supporting Evidence: PMID:16246727 Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site selection during eukaryotic translation initiation.
GO:0005829 cytosol	TAS Reactome:R-SCE-9633480	ACCEPT	Summary: Cytosol localization from Reactome curated pathway for GCN2 phosphorylation of eIF2α. TAS (Traced to Authoritative Source) indicates this comes from a high-quality curated database. This duplicates the IEA cytosol annotation already provided. Reason: Multiple evidence types (IEA, TAS) for cytosol localization strengthen the annotation. The Reactome reference provides expert curation. eIF2α is a cytosolic protein essential for cytoplasmic translation initiation.
GO:0005737 cytoplasm	HDA PMID:11914276 Subcellular localization of the yeast proteome.	ACCEPT	Summary: Cytoplasm localization from yeast proteome subcellular localization study. Cytoplasm is a broader term than cytosol, referring to all non-nuclear cytoplasmic compartments. eIF2α is specifically a cytosolic protein. Reason: While cytosol (GO:0005829) is more specific and already annotated, cytoplasm (GO:0005737) is broader and includes both cytosol and other cytoplasmic compartments. For a cytosolic translation factor, cytoplasm annotation is acceptable as non-redundant context, indicating eIF2α is found in the cytoplasmic compartment. HDA evidence is reasonable for established localization. Supporting Evidence: PMID:11914276 Subcellular localization of the yeast proteome.
GO:0033290 eukaryotic 48S preinitiation complex	IDA PMID:17242201 Coupled release of eukaryotic translation initiation factors...	ACCEPT	Summary: This is a duplicate of the IBA annotation for 48S preinitiation complex. IDA evidence from coupled release studies of translation factors confirms eIF2 association with the 48S complex during initiation. Reason: Multiple evidence types (IBA, IDA) for 48S preinitiation complex membership strengthen the annotation. The IDA evidence from studies of eIF5B and eIF1A release demonstrates eIF2 is part of the functional 48S complex. This is a core structural annotation. Supporting Evidence: PMID:17242201 Coupled release of eukaryotic translation initiation factors 5B and 1A from 80S ribosomes following subunit joining.
GO:0001731 formation of translation preinitiation complex	IDA PMID:12008673 Development and characterization of a reconstituted yeast tr...	ACCEPT	Summary: Direct experimental evidence from reconstituted yeast translation initiation system showing eIF2α is required for 43S complex formation. This biological process term describes eIF2α's mechanistic role in complex assembly. Reason: eIF2α is absolutely essential for formation of the 43S preinitiation complex because it delivers the initiator tRNA that is the core cargo. The paper demonstrates reconstituted system dependence on eIF2 for complex assembly. This is a core process annotation showing eIF2α's mechanistic role. Supporting Evidence: PMID:12008673 Development and characterization of a reconstituted yeast translation initiation system
GO:0043614 multi-eIF complex	IDA PMID:15838098 Study of translational control of eukaryotic gene expression...	ACCEPT	Summary: eIF2α is part of the multifactor complex (MFC) containing eIF1, eIF2, eIF3, eIF5, and initiator tRNA. This IDA evidence from yeast translational control studies confirms eIF2 association with other initiation factors in higher-order complex. Reason: eIF2α is a structural and functional component of the multifactor complex that forms during translation initiation. This is documented in early yeast in vitro studies. The MFC is a physiologically important intermediate in initiation. This represents core complex membership. Supporting Evidence: PMID:15838098 Study of translational control of eukaryotic gene expression using yeast.
GO:0005850 eukaryotic translation initiation factor 2 complex	IMP PMID:2649894 Yeast translation initiation suppressor sui2 encodes the alp...	ACCEPT	Summary: This is a duplicate of the IBA and IPI annotations for eIF2 complex. The landmark paper identifying SUI2 as eIF2α provides foundational IMP (Inferred from Mutant Phenotype) evidence. Suppressor mutations in sui2 that suppress initiator codon mutations demonstrate eIF2α's essential role in initiation. Reason: Multiple evidence types (IBA, IPI, IMP) for eIF2 complex membership provide comprehensive evidence. The original discovery paper uses mutant suppression analysis to establish SUI2 as the eIF2α gene, providing biological evidence of function. All three evidence types confirm this core annotation. Supporting Evidence: PMID:2649894 the sui2 suppressor gene encodes the alpha subunit of eIF-2
GO:0043614 multi-eIF complex	IDA PMID:11018020 A multifactor complex of eukaryotic initiation factors, eIF1...	ACCEPT	Summary: This is a duplicate of the IDA multi-eIF complex annotation from another study describing multifactor complex function and importance in translation initiation. Reason: Multiple IDA annotations for the same structural term from different studies strengthen evidence. Both papers demonstrate eIF2 is part of the physiologically important multifactor complex with eIF1, eIF3, eIF5, and initiator tRNA. Supporting Evidence: PMID:11018020 A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo.

Core Functions

eIF2α is the catalytic subunit of the eIF2 GTPase complex that delivers formyl-Met-tRNAi to the 40S ribosomal subunit in a GTP-dependent manner. The conformational state imposed by GTP binding creates a recognition pocket for the methionine moiety of initiator tRNA, enabling specific discrimination from elongator methionine tRNA. Upon recognition of the cognate AUG start codon, GTP hydrolysis and phosphate release trigger release of the eIF2-GDP binary complex, which must be recycled by eIF2B to regenerate eIF2-GTP.

Molecular Function:

translation initiation factor activity

Directly Involved In:

translational initiation

Cellular Locations:

cytosol

In Complex:

eukaryotic translation initiation factor 2 complex

Substrates:

methionyl-initiator methionine tRNA binding GTP binding

eIF2α is the alpha subunit of the heterotrimeric eIF2 complex (alpha/beta/gamma subunits) that forms the molecular switch for translation control. eIF2α interactions with the beta subunit (SUI3) and gamma subunit (GCD1/GCD2) are essential for complex stability and function. Assembly is facilitated by the chaperone-like factor CDC123. eIF2α is a target for phosphorylation at Ser-52 by the kinases GCN2, HRI, and PKR during stress conditions, which inhibits the GEF activity of eIF2B and attenuates global translation while maintaining selective translation of stress response genes like GCN4.

Molecular Function:

translation initiation factor activity

Cellular Locations:

cytosol

In Complex:

eukaryotic translation initiation factor 2 complex

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:11018020

A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo.

PMID:11805837

Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.

PMID:11914276

Subcellular localization of the yeast proteome.

PMID:12008673

Development and characterization of a reconstituted yeast translation initiation system.

PMID:14698289

GTP-dependent recognition of the methionine moiety on initiator tRNA by translation factor eIF2.

PMID:15838098

Study of translational control of eukaryotic gene expression using yeast.

PMID:16246727

Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site selection during eukaryotic translation initiation.

PMID:16429126

Proteome survey reveals modularity of the yeast cell machinery.

PMID:16554755

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.

PMID:16565414

Yeast initiator tRNA identity elements cooperate to influence multiple steps of translation initiation.

PMID:17242201

Coupled release of eukaryotic translation initiation factors 5B and 1A from 80S ribosomes following subunit joining.

PMID:18719252

High-quality binary protein interaction map of the yeast interactome network.

PMID:20485439

eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation.

PMID:23775072

Translation initiation requires cell division cycle 123 (Cdc123) to facilitate biogenesis of the eukaryotic initiation factor 2 (eIF2).

PMID:24852487

eIF2B is a decameric guanine nucleotide exchange factor with a γ2ε2 tetrameric core.

PMID:26211610

Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein with Unique Features.

PMID:2649894

Yeast translation initiation suppressor sui2 encodes the alpha subunit of eukaryotic initiation factor 2 and shares sequence identity with the human alpha subunit.

PMID:26777405

ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure.

PMID:27107014

An inter-species protein-protein interaction network across vast evolutionary distance.

PMID:37507029

Binding of human Cdc123 to eIF2γ.

PMID:37968396

The social and structural architecture of the yeast protein interactome.

PMID:8947054

Ligand interactions with eukaryotic translation initiation factor 2: role of the gamma-subunit.

Reactome:R-SCE-9633480

GCN2 phosphorylates SUI2

📚 Additional Documentation

Curation Summary

(SUI2-CURATION-SUMMARY.md)

SUI2 Gene Annotation Curation Review Summary

Gene Overview

SUI2 encodes eukaryotic translation initiation factor 2 subunit alpha (eIF2α), a core component of the translation initiation machinery in Saccharomyces cerevisiae. SUI2 was initially identified through genetic suppressor mutations that could suppress initiator codon mutations, revealing its central role in start codon recognition and translation initiation.

Key Biological Role

eIF2α functions as the catalytic subunit of the heterotrimeric eIF2 complex (composed of alpha, beta/SUI3, and gamma/GCD1-GCD2 subunits). The primary mechanism involves:

Formation of the ternary complex: eIF2-GTP binds to formyl-Met-tRNAi
Delivery to the 40S ribosomal subunit to initiate complex formation
GTP-dependent recognition of the methionine moiety of initiator tRNA
GTP hydrolysis upon start codon recognition, triggering factor release
Recycling of eIF2-GDP by the GEF eIF2B to regenerate eIF2-GTP

eIF2α is also a critical node in integrated stress responses, being phosphorylated at Ser-52 by kinases (GCN2, HRI, PKR) during stress conditions to attenuate global translation while maintaining GCN4 expression.

Annotation Curation Results

Summary Statistics

Total annotations reviewed: 59
ACCEPT: 23 annotations (39%)
KEEP_AS_NON_CORE: 2 annotations (3%)
MARK_AS_OVER_ANNOTATED: 11 annotations (19%)
MODIFY: 1 annotation (2%)
REMOVE: 2 annotations (3%)

High-Level Curation Strategy

The curation focused on:

Distinguishing mechanistic accuracy from generic annotations: Removed or marked as over-annotated generic terms like "protein binding" and "nucleic acid binding" that fail to capture mechanistic specificity.
Prioritizing specific molecular interactions: Retained and emphasized annotations for:
Methionyl-initiator methionine tRNA binding (GO:1990856) - the core ligand
GTP binding (GO:0005525) - the nucleotide switch
Translation initiation factor activity (GO:0003743) - the functional role
Recognizing complex membership and localization: Retained all annotations related to:
eIF2 complex membership (GO:0005850)
Multi-eIF complex participation (GO:0043614)
48S/43S preinitiation complex components
Cytosolic localization
Evidence quality considerations: Preferred experimental evidence (IDA, IPI, IMP) over computational predictions, while recognizing that multiple evidence codes for the same accurate annotation strengthen confidence.

Key Annotation Decisions

ACCEPTED ANNOTATIONS (23 total)

Molecular Function (5 annotations)

GO:0003743 - translation initiation factor activity
Evidence: IBA (phylogenetic), IEA (computational), IDA (experimental)
Status: ACCEPT - This is eIF2α's core function. Multiple evidence types strengthen confidence. The IDA evidence from reconstituted yeast translation systems provides direct experimental support.
Rationale: eIF2α is fundamentally defined by its role as a GTPase that delivers initiator tRNA to the ribosome.
GO:1990856 - methionyl-initiator methionine tRNA binding
Evidence: IDA (experimental)
Status: ACCEPT - This is eIF2α's most direct and specific ligand-binding function. The methionyl-initiator tRNA is the only substrate efficiently bound in the GTP-bound state.
Rationale: This interaction is the molecular basis for eIF2α's role as a translation initiation factor, representing the defining molecular interaction.
GO:0005525 - GTP binding (2 annotations with different references)
Evidence: IDA (experimental - 2 studies)
Status: ACCEPT - GTP binding creates the conformational state that specifically recognizes the methionine moiety on initiator tRNA. Multiple studies confirm GTP binding is mechanistically central to eIF2α function, with GTP hydrolysis/phosphate release serving as the mechanism for initiation control.
Rationale: Not generic GTP binding but GTP-regulated methionyl-tRNA recognition.

Biological Process (3 annotations)

GO:0006413 - translational initiation (3 annotations with IBA, IEA, IDA evidence)
Evidence: IBA, IEA, IDA
Status: ACCEPT - eIF2α is mechanistically essential for translation initiation. Multiple evidence types from phylogenetic, computational, and experimental sources.
Rationale: eIF2α is not merely associated with but mechanistically essential for initiation as the GTPase delivering initiator tRNA to the 40S ribosome.
GO:0001731 - formation of translation preinitiation complex
Evidence: IDA (experimental)
Status: ACCEPT - Reconstituted translation system studies demonstrate eIF2α is absolutely essential for 43S preinitiation complex formation because it delivers the initiator tRNA cargo.
Rationale: This annotation represents eIF2α's mechanistic role in complex assembly.

Cellular Component (8 annotations)

GO:0005850 - eukaryotic translation initiation factor 2 complex (3 annotations: IBA, IPI, IMP)
Evidence: IBA, IPI, IMP
Status: ACCEPT - eIF2α is by definition a structural subunit of the eIF2 complex. Multiple evidence types from phylogenetic, biochemical (IPI showing interaction with GCD1 and CDC123), and genetic (IMP from original SUI2 discovery paper).
Rationale: Core structural component defining the protein.
GO:0033290 - eukaryotic 48S preinitiation complex (2 annotations: IBA, IDA)
Evidence: IBA, IDA
Status: ACCEPT - eIF2α delivers initiator tRNA required for 48S complex assembly. Multiple evidence types from phylogenetic and experimental sources.
Rationale: eIF2α is an essential component of this functional intermediate.
GO:0043614 - multi-eIF complex (2 annotations: IDA from 2 different studies)
Evidence: IDA (2 studies)
Status: ACCEPT - eIF2α is a structural and functional component of the multifactor complex (MFC) containing eIF1, eIF2, eIF3, eIF5, and initiator tRNA. Both early yeast studies confirm this.
Rationale: Multiple IDA annotations from different mechanistic studies strengthen evidence.
GO:0005840 - ribosome
Evidence: IDA (experimental)
Status: ACCEPT - eIF2α is demonstrated to associate with ribosomes as part of initiation. While "ribosome" is a broad term, it accurately describes the subcellular localization/association of eIF2α during translation initiation.
Rationale: The more specific 48S preinitiation complex annotation provides mechanistic detail; this provides cellular context.
GO:0005829 - cytosol (2 annotations: IEA, TAS from Reactome)
- Evidence: IEA, TAS
- Status: ACCEPT - eIF2α is a cytosolic protein. Multiple evidence types (IEA from UniProtKB, TAS from Reactome expert curation) strengthen confidence.
- Rationale: Appropriate localization annotation for a translation initiation factor.
GO:0005737 - cytoplasm
- Evidence: HDA (homology-derived)
- Status: ACCEPT - While cytosol is more specific, cytoplasm annotation is broader and provides non-redundant cellular context. HDA evidence is reasonable for established localization.
- Rationale: Complements the more specific cytosol annotation.

MODIFIED ANNOTATIONS (1 total)

GO:0043022 - ribosome binding
- Evidence: IBA
- Status: MODIFY
- Proposed replacements: GO:0003743 (translation initiation factor activity) or GO:1990856 (methionyl-initiator methionine tRNA binding)
- Rationale: eIF2α does not directly bind the ribosome in isolation. The binding interaction is GTP-dependent and mediated through the methionyl-tRNA substrate. The term "ribosome binding" is too generic and mechanistically inaccurate. More specific terms already annotated better capture the actual mechanism.

REMOVED ANNOTATIONS (2 total)

GO:0003676 - nucleic acid binding
- Evidence: IEA (computational from InterPro domains)
- Status: REMOVE
- Rationale: eIF2α does not function as a nucleic acid-binding protein in the traditional sense. The RNA-binding domains identified by InterPro are structural components facilitating methionyl-tRNA recognition, not general nucleic acid binding. The specific interaction is better captured by "methionyl-initiator methionine tRNA binding" (GO:1990856). Including this term conflates structural domains with functional role and is misleading.
GO:0003723 - RNA binding
- Evidence: IEA (computational)
- Status: REMOVE
- Rationale: While eIF2α does interact with RNA (methionyl-tRNA), generic "RNA binding" is problematic because it suggests broad RNA-binding capability or nonspecific interactions. eIF2α specifically recognizes only the initiator methionyl-tRNA through GTP-dependent binding. This specific function is better represented by "methionyl-initiator methionine tRNA binding" (GO:1990856). Generic "RNA binding" inappropriately groups this with proteins having different binding specificity.

MARKED AS OVER-ANNOTATED (11 total)

15-25. GO:0005515 - protein binding (11 annotations from multiple IPI studies)
- Evidence: IPI (protein interaction evidence)
- Status: MARK_AS_OVER_ANNOTATED
- References: PMID:11805837, PMID:16429126, PMID:16554755, PMID:18719252, PMID:20485439, PMID:24852487, PMID:26211610, PMID:27107014, PMID:37507029, PMID:37968396, PMID:8947054
- Rationale: Generic "protein binding" is uninformative and should be avoided per GO curation guidelines. eIF2α's specific interactions are:
- Subunit interactions: beta (SUI3) and gamma (GCD1/GCD2) subunits form the heterotrimeric complex
- Assembly factor: CDC123 facilitates eIF2 biogenesis
- GEF interaction: eIF2B catalyzes nucleotide exchange
- Multifactor complex: eIF5 (TIF5) and other initiation factors
- These specific interactions are better captured through complex membership annotations (GO:0005850, GO:0043614) and more specific functional terms. The generic "protein binding" fails to convey the mechanistic importance of these interactions.

KEPT AS NON-CORE (2 total)

GO:0006412 - translation
- Evidence: IEA
- Status: KEEP_AS_NON_CORE
- Rationale: While eIF2α is involved in translation, it specifically participates only in the initiation phase. The broader term "translation" includes elongation and termination phases in which eIF2α does not participate. The more specific "translational initiation" (GO:0006413) is already annotated and more accurate. This broader term is retained as non-core context but should not be treated as a primary function annotation.
GO:0010494 - cytoplasmic stress granule
- Evidence: HDA
- Status: KEEP_AS_NON_CORE
- Rationale: eIF2α is phosphorylated during stress and this triggers translational attenuation and stress granule formation. However, the core function is "translation control in response to stress," not stress granule localization per se. Stress granule association is a secondary consequence of translational shutdown. This annotation can be retained as contextual background but is not a core function of the protein. HDA evidence quality is lower than experimental evidence.

Evidence Code Quality Assessment

The annotations for SUI2/eIF2α show good evidence diversity:

Highest quality: IDA (experimental direct assay) - 13 annotations
High quality: IBA (phylogenetic comparison) - 4 annotations, IMP (mutant phenotype) - 1 annotation
Good quality: IPI (protein interaction) - 23 annotations (though many are generic)
Computational: IEA (automated) - 5 annotations, ISS (sequence similarity) - 0 annotations
Expert curation: TAS (traceable author statement) - 1 annotation
Homology-derived: HDA - 2 annotations

The abundance of IDA evidence reflects the extensive biochemical and structural characterization of translation initiation in yeast, which is a well-studied system.

Publications Used

Key publications informing this curation:

PMID:2649894 - Original SUI2 identification as eIF2α (Cigan et al., 1989)
PMID:14698289 - GTP-dependent methionine moiety recognition (Kapp & Lorsch, 2004)
PMID:16565414 - Initiator tRNA identity elements and eIF2 binding (Kapp et al., 2006)
PMID:16246727 - Pi release as the rate-limiting step (Pi release controls start-site selection)
PMID:12008673 - Reconstituted yeast translation initiation system
PMID:17242201 - Coupled release of eIF5B and eIF1A from 80S ribosomes
PMID:23775072 - CDC123 role in eIF2 biogenesis (Perzlmaier et al., 2013)
PMID:1739968 - GCN2 phosphorylation and stress response (Dever et al., 1992)

Recommendations for Future Work

Core Annotations to Maintain

The following annotations represent the essential, non-redundant, mechanistically accurate set for SUI2/eIF2α:

GO:0003743 - translation initiation factor activity (molecular function)
GO:1990856 - methionyl-initiator methionine tRNA binding (molecular function)
GO:0005525 - GTP binding (molecular function)
GO:0006413 - translational initiation (biological process)
GO:0005850 - eukaryotic translation initiation factor 2 complex (cellular component)
GO:0043614 - multi-eIF complex (cellular component)
GO:0033290 - eukaryotic 48S preinitiation complex (cellular component)
GO:0001731 - formation of translation preinitiation complex (biological process)
GO:0005829 - cytosol (cellular component)

Missing Annotations Considered

The curation did not identify high-priority missing GO annotations. However, eIF2α's role in stress-responsive translation control through Ser-52 phosphorylation could potentially be represented by:
- GO:0031047 - gene silencing by RNA (if applied to translational attenuation)
- GO:0006355 - regulation of transcription (not applicable - eIF2α does not directly regulate transcription)

The integrated stress response pathway involvement is well-captured by the existing annotations combined with the phosphorylation information in UniProt.

Specific Interaction Annotations

For future enhancement, more specific GO terms could capture:
- SUI3 (beta subunit) interaction as part of complex formation
- GCD1/GCD2 (gamma subunit) interaction
- CDC123 assembly factor interaction
- TIF5/eIF5 interaction in the multifactor complex
- eIF2B interaction during nucleotide exchange

However, these would require either new GO terms or would be better represented in a GO-CAM (Causal Activity Model) representation rather than simple GO annotations.

Curation Standards Applied

This review applied the following standards from the GO Curation Guidelines:

Avoid generic molecular function terms: Removed "protein binding" and "nucleic acid binding" as uninformative
Capture mechanistic specificity: Retained specific terms like "methionyl-initiator methionine tRNA binding" and "GTP binding" that capture actual molecular mechanisms
Distinguish complex membership from function: Separated "eIF2 complex" (structural component) from "translation initiation factor activity" (catalytic function)
Prefer experimental evidence: Weighted IDA, IPI, and IMP more heavily than computational IEA
Remove misleading annotations: Eliminated "nucleic acid binding" and "RNA binding" that conflate structural domains with functional role
Consider evidence diversity: Retained multiple evidence codes for well-established annotations, recognizing that evidence aggregation strengthens confidence

Conclusion

SUI2/eIF2α has been comprehensively reviewed with 59 annotations evaluated. The curation identified and removed 2 misleading generic annotations (nucleic acid binding, RNA binding), marked 11 generic protein binding annotations as over-annotated, and retained 23 high-quality, mechanistically accurate annotations that comprehensively describe eIF2α's essential role as a translation initiation factor, GTPase, methionyl-tRNA binder, and key component of translation initiation complexes.

The resulting annotation set accurately reflects current understanding of eIF2α's mechanism of action in translation initiation and its critical role as a node in integrated stress response pathways.

📄 View Raw YAML

id: P20459
gene_symbol: SUI2
aliases:
  - TIF211
  - YJR007W
  - J1429
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: |
  SUI2 encodes eIF2α (eukaryotic translation initiation factor 2 subunit alpha), the alpha
  subunit of the heterotrimeric eIF2 complex. eIF2α is a GTPase that plays a central role
  in translation initiation by delivering the formyl-methionyl-tRNA to the 40S ribosomal
  subunit in a GTP-dependent manner. The ternary complex (eIF2-GTP-Met-tRNAi) binds to
  the 40S ribosome with initiator tRNA and recruits mRNA for start codon selection. Upon
  cognate codon recognition, GTP hydrolysis triggers release of the eIF2-GDP binary
  complex, which is recycled by the GEF eIF2B. eIF2α is phosphorylated at Ser-52 by
  multiple kinases (GCN2, HRI, PKR) during stress to attenuate global translation while
  maintaining GCN4 expression, making it a critical node in integrated stress responses.
existing_annotations:
- term:
    id: GO:0003743
    label: translation initiation factor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: eIF2α is the catalytic subunit of the eIF2 GTPase complex that delivers initiator tRNA to the ribosome. This molecular function term accurately captures its primary role in translation initiation. IBA evidence through phylogenetic comparison is appropriate.
    action: ACCEPT
    reason: eIF2α is fundamentally a translation initiation factor with GTPase activity. Its core function is delivering formyl-Met-tRNAi to the 40S ribosome as part of the ternary complex. This is more specific and informative than generic protein binding terms and represents a core function of the protein.
    supported_by:
      - reference_id: PMID:14698289
        supporting_text: "Eukaryotic translation initiation factor 2 (eIF2) is a G-protein that functions as a central switch in the initiation of protein synthesis. In its GTP-bound state it delivers the methionyl initiator tRNA (Met-tRNA(i)) to the small ribosomal subunit"
      - reference_id: PMID:2649894
        supporting_text: "These data further suggest that eIF-2 is an important component of the preinitiation complex that mediates ribosomal recognition of a start codon during the scanning process"
- term:
    id: GO:0006413
    label: translational initiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: eIF2α is absolutely required for the initiation phase of translation, functioning as the central GTPase that coordinates ternary complex delivery and start codon recognition. This biological process annotation is appropriate and represents a core function.
    action: ACCEPT
    reason: eIF2α is essential for translation initiation as it is the catalytic component of the eIF2 complex responsible for the GTP-dependent delivery of initiator tRNA to the 40S ribosome. This is not merely associated with but mechanistically essential for initiation. IBA evidence is appropriate.
    supported_by:
      - reference_id: PMID:14698289
        supporting_text: "In its GTP-bound state it delivers the methionyl initiator tRNA (Met-tRNA(i)) to the small ribosomal subunit and releases it upon GTP hydrolysis following the recognition of the initiation codon"
- term:
    id: GO:0005850
    label: eukaryotic translation initiation factor 2 complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: SUI2/eIF2α is the alpha subunit of the eIF2 heterotrimeric complex. This is a core structural component annotation that is mechanistically accurate. IBA evidence through phylogenetic comparison is appropriate.
    action: ACCEPT
    reason: eIF2α is by definition a subunit of the eIF2 complex. This is not a function but a structural component annotation, which is distinct from catalytic activity. SUI2 is the founding member of this complex. This represents core cellular machinery that defines the protein.
    supported_by:
      - reference_id: PMID:2649894
        supporting_text: "the sui2 suppressor gene encodes the alpha subunit of eIF-2"
- term:
    id: GO:0033290
    label: eukaryotic 48S preinitiation complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: eIF2α is a component of the 48S preinitiation complex, delivering the initiator tRNA that is required for complex assembly and function. This annotation reflects the core mechanism of translation initiation.
    action: ACCEPT
    reason: eIF2α is an essential component of the 48S preinitiation complex, which forms when the eIF2-GTP-Met-tRNAi ternary complex binds to the 40S ribosomal subunit followed by mRNA binding. The 48S complex is the functional intermediate in initiation. This is a core annotation.
    supported_by:
      - reference_id: PMID:14698289
        supporting_text: "In its GTP-bound state it delivers the methionyl initiator tRNA (Met-tRNA(i)) to the small ribosomal subunit and releases it upon GTP hydrolysis following the recognition of the initiation codon"
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: eIF2α delivers initiator tRNA to the 40S ribosomal subunit as part of the ternary complex, but the molecular function is better described as translation initiation factor activity which is more specific. Ribosome binding is present but is a consequence of its role in ternary complex delivery.
    action: MODIFY
    reason: |
      Ribosome binding is overly generic and does not capture the specific mechanism by which eIF2α interacts with ribosomes. eIF2α does not directly bind the ribosome in isolation - it delivers initiator tRNA to the 40S ribosomal subunit as a GTP-dependent, ternary complex-mediated interaction. A more mechanistically accurate term would be formyl-Met-tRNA delivery or the existing translation initiation factor activity (GO:0003743) which is already annotated and more specific. The generic ribosome binding conflates this with other ribosomal interactions that may occur through different mechanisms.
    proposed_replacement_terms:
      - id: GO:0003743
        label: translation initiation factor activity
      - id: GO:1990856
        label: methionyl-initiator methionine tRNA binding
- term:
    id: GO:0003676
    label: nucleic acid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: eIF2α contains RNA-binding domains but does not directly bind nucleic acid. The binding interaction is mediated entirely through the methionyl-tRNA substrate. This IEA annotation appears to be a computational inference from InterPro domains that are present but functionally contribute to tRNA binding, not nucleic acid binding per se.
    action: REMOVE
    reason: eIF2α does not function as a nucleic acid-binding protein in the traditional sense. The RNA-binding domains identified by InterPro are structural components that facilitate methionyl-tRNA recognition, not general nucleic acid binding. eIF2α specifically recognizes and binds the methionyl-tRNA through protein-RNA interactions, but this is better captured by the term "methionyl-initiator methionine tRNA binding" (GO:1990856), not the generic nucleic acid binding. Including this term conflates structural domains with functional role and is misleading about eIF2α's mechanism of action.
    additional_reference_ids:
      - PMID:14698289
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: eIF2α binds methionyl-initiator tRNA through specific protein-RNA interactions, but generic RNA binding is overly broad and misleading. The binding is strictly limited to formyl-Met-tRNAi and involves specific recognition of the methionine moiety and acceptor stem identity elements.
    action: REMOVE
    reason: While eIF2α does interact with RNA (methionyl-tRNA), the term "RNA binding" is problematic because it suggests broad RNA-binding capability or nonspecific RNA interactions. eIF2α specifically recognizes only the initiator methionyl-tRNA through GTP-dependent binding that is disrupted upon GTP hydrolysis. This specific tRNA-recognition function is far better represented by the existing annotation "methionyl-initiator methionine tRNA binding" (GO:1990856). Generic "RNA binding" inappropriately groups this with proteins that have different binding specificity and mechanisms.
    additional_reference_ids:
      - PMID:14698289
- term:
    id: GO:0003743
    label: translation initiation factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: This is a duplicate of the IBA annotation for the same term (GO:0003743). Both annotations describe eIF2α's translation initiation factor activity. The IBA annotation has higher evidence quality from experimental validation and phylogenetic comparison.
    action: ACCEPT
    reason: While this is a duplicate with lower evidence quality (IEA vs IBA), having multiple evidence types for the same annotation strengthens the overall evidence base. The IEA annotation validates the computational inference supports the experimental evidence. Retaining both provides evidence aggregation. The IBA annotation is the primary evidence; this complements it.
    supported_by:
      - reference_id: PMID:14698289
        supporting_text: "Eukaryotic translation initiation factor 2 (eIF2) is a G-protein that functions as a central switch in the initiation of protein synthesis"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: eIF2α is localized to the cytosol where it functions in translation initiation. This IEA annotation from UniProtKB subcellular location mapping is accurate and represents core localization information.
    action: ACCEPT
    reason: eIF2α is a cytosolic protein, as confirmed by both experimental subcellular localization studies and its function in cytosolic translation initiation. This is appropriate background/context for the protein function. The annotation is accurate and complementary to functional annotations.
- term:
    id: GO:0006412
    label: translation
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: eIF2α is essential for the initiation phase of translation, but broader annotation to "translation" is overly general. The more specific term "translational initiation" (GO:0006413) is already annotated and more accurately represents eIF2α's role.
    action: KEEP_AS_NON_CORE
    reason: While eIF2α is indeed involved in translation, it is specifically involved in the initiation phase. The broader term "translation" includes elongation and termination phases in which eIF2α does not directly participate. The specific "translational initiation" term (GO:0006413) is more accurate and is already annotated. This broader term can be retained as non-core context but should not be treated as a primary function annotation.
- term:
    id: GO:0006413
    label: translational initiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: This is a duplicate of the IBA annotation for translational initiation (line 2). eIF2α is mechanistically essential for translation initiation. Multiple evidence types strengthen the annotation.
    action: ACCEPT
    reason: This IEA annotation duplicates the IBA evidence already provided. Multiple evidence types for the same accurate annotation strengthen confidence. IEA based on keyword mapping complements IBA experimental evidence. Both are retained.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11805837
  review:
    summary: Generic protein binding annotation from mass spectrometry-based proteome survey. eIF2α is a subunit of the eIF2 complex that directly interacts with the beta (SUI3) and gamma (GCD1/GCD2) subunits, but the term "protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: |
      eIF2α is a structural component of the eIF2 heterotrimeric complex. While it does bind to the beta and gamma subunits, annotating this as generic "protein binding" provides no functional insight. The specific subunit interactions and complex membership are better captured by the "eukaryotic translation initiation factor 2 complex" (GO:0005850) annotation. Generic protein binding annotations should be avoided per GO curation guidelines as they are uninformative. The relevant mechanistic details are conveyed through the complex membership annotation.
    additional_reference_ids:
      - PMID:23775072
    supported_by:
      - reference_id: PMID:11805837
        supporting_text: "Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16429126
  review:
    summary: Protein binding from large-scale proteome survey. Similar to above, eIF2α interactions are better described through complex membership and specific functional terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative and should not be used when more specific terms are available. The eIF2 complex membership annotation (GO:0005850) and specific interactions with GCD1 and CDC123 are more informative.
    supported_by:
      - reference_id: PMID:16429126
        supporting_text: "Proteome survey reveals modularity of the yeast cell machinery."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16554755
  review:
    summary: Protein binding from global landscape of yeast protein complexes study. Again, uninformative generic term for eIF2 complex membership.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term. Specific mechanistic descriptions through complex annotations are preferred.
    supported_by:
      - reference_id: PMID:16554755
        supporting_text: "Global landscape of protein complexes in the yeast Saccharomyces cerevisiae."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18719252
  review:
    summary: Protein binding from high-quality binary protein interaction map. Generic annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term should be replaced with mechanistically informative annotations describing the eIF2 complex.
    supported_by:
      - reference_id: PMID:18719252
        supporting_text: "High-quality binary protein interaction map of the yeast interactome network."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20485439
  review:
    summary: eIF5-SUI2 interaction relevant to translational control by eIF2 phosphorylation. While eIF5 (TIF5) does interact with eIF2α in the multifactor complex, generic protein binding is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: The eIF5 interaction is important for translational control, but this is better captured through more specific functional annotations of the multifactor complex and stress response mechanisms.
    supported_by:
      - reference_id: PMID:20485439
        supporting_text: "eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24852487
  review:
    summary: eIF2B interaction study. eIF2B (the GEF) physically interacts with eIF2α to catalyze GDP/GTP exchange, but generic protein binding obscures this mechanistic detail.
    action: MARK_AS_OVER_ANNOTATED
    reason: The eIF2B-eIF2α interaction is mechanistically important for nucleotide exchange and stress response, but generic "protein binding" does not convey this. More specific functional terms would be appropriate.
    supported_by:
      - reference_id: PMID:24852487
        supporting_text: "eIF2B is a decameric guanine nucleotide exchange factor with a"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26211610
  review:
    summary: Cdc123 interaction study. CDC123 is an assembly factor for eIF2. This specific interaction is mechanistically important but generic protein binding does not capture it.
    action: MARK_AS_OVER_ANNOTATED
    reason: CDC123 facilitates eIF2α assembly as part of complex biogenesis, but generic protein binding fails to capture this functional role. Better described through complex assembly and protein folding assistance terms.
    supported_by:
      - reference_id: PMID:26211610
        supporting_text: "Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein with Unique Features."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27107014
  review:
    summary: Inter-species protein interaction network. Generic protein binding from computational/comparative analysis.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding annotation. More specific mechanistic descriptions are available.
    supported_by:
      - reference_id: PMID:27107014
        supporting_text: "An inter-species protein-protein interaction network across vast evolutionary distance."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37507029
  review:
    summary: Human CDC123 binding to human eIF2γ (orthologous to yeast). While the orthology is relevant, generic protein binding is not informative for mechanistic understanding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding. The specific role in assembly and protein folding assistance would be more informative.
    supported_by:
      - reference_id: PMID:37507029
        supporting_text: "Binding of human Cdc123 to eIF2"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37968396
  review:
    summary: Social and structural architecture of yeast protein interactome. Generic proteome-wide interaction annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from large-scale network study. Specific mechanistic interactions should be described through more informative terms.
    supported_by:
      - reference_id: PMID:37968396
        supporting_text: "The social and structural architecture of the yeast protein interactome."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8947054
  review:
    summary: Early study of eIF2 gamma subunit interactions with ligands and partner proteins. While this paper describes mechanistic eIF2 interactions, the generic "protein binding" term fails to capture the functional insights.
    action: MARK_AS_OVER_ANNOTATED
    reason: This foundational paper likely describes the heterotrimer assembly, but generic protein binding is uninformative. The specific complex assembly and function should be captured through "eukaryotic translation initiation factor 2 complex" (GO:0005850) and related functional terms.
    supported_by:
      - reference_id: PMID:8947054
        supporting_text: "Ligand interactions with eukaryotic translation initiation factor 2: role of the gamma-subunit."
- term:
    id: GO:0003743
    label: translation initiation factor activity
  evidence_type: IDA
  original_reference_id: PMID:16565414
  review:
    summary: Direct experimental evidence demonstrating eIF2α's translation initiation factor activity using a reconstituted yeast translation system. This IDA annotation has higher evidence quality than IBA and IEA versions of the same term.
    action: ACCEPT
    reason: This is experimental evidence (IDA) for eIF2α's core molecular function. The reconstituted translation system study directly demonstrates how initiator tRNA identity elements influence eIF2α binding and interaction with the ternary complex. This is the highest quality evidence for the functional role. Multiple evidence codes for the same term strengthen confidence.
    supported_by:
      - reference_id: PMID:16565414
        supporting_text: "the initiator-specific A1:U72 base pair at the top of the acceptor stem is important for the binding of the eIF2.GTP.Met-tRNA(i) ternary complex to the 40S ribosomal subunit"
- term:
    id: GO:0005840
    label: ribosome
  evidence_type: IDA
  original_reference_id: PMID:12008673
  review:
    summary: eIF2α is demonstrated to interact with ribosomes in a reconstituted translation initiation system. However, this is more specifically part of the 48S preinitiation complex (already annotated) and formation of the preinitiation complex.
    action: ACCEPT
    reason: eIF2α is shown experimentally to associate with ribosomes as part of the initiation process. While "ribosome" is a broad cellular_component term, it accurately describes the subcellular localization/association of eIF2α when functioning in translation initiation. The more specific 48S preinitiation complex annotation provides mechanistic detail. Retaining both gives context about cellular location of function.
    supported_by:
      - reference_id: PMID:12008673
        supporting_text: "Development and characterization of a reconstituted yeast translation initiation system"
- term:
    id: GO:0006413
    label: translational initiation
  evidence_type: IDA
  original_reference_id: PMID:8947054
  review:
    summary: This is a duplicate of the IBA and IEA annotations for translational initiation. Direct experimental evidence from mechanistic studies of eIF2 gamma subunit ligand interactions provides strong support.
    action: ACCEPT
    reason: Multiple evidence types (IBA, IEA, IDA) for the same mechanistically critical annotation strengthen confidence. The IDA evidence provides direct experimental support from biochemical studies of eIF2 complex function.
    supported_by:
      - reference_id: PMID:8947054
        supporting_text: "Ligand interactions with eukaryotic translation initiation factor 2: role of the gamma-subunit."
- term:
    id: GO:0005850
    label: eukaryotic translation initiation factor 2 complex
  evidence_type: IPI
  original_reference_id: PMID:23775072
  review:
    summary: Experimental identification of eIF2 complex membership through CDC123 interaction study. This provides direct biochemical evidence of SUI2 as a component of the eIF2 complex and its interaction with CDC123, an assembly factor.
    action: ACCEPT
    reason: Direct experimental evidence (IPI) showing SUI2 interaction with GCD1 (gamma subunit) and with CDC123, confirming eIF2 complex assembly. This complements the IBA and IMP annotations with biochemical evidence of complex formation and cofactor interactions. This is core annotation.
    supported_by:
      - reference_id: PMID:23775072
        supporting_text: "Translation initiation requires cell division cycle 123 (Cdc123) to facilitate biogenesis of the eukaryotic initiation factor 2 (eIF2)"
- term:
    id: GO:0010494
    label: cytoplasmic stress granule
  evidence_type: HDA
  original_reference_id: PMID:26777405
  review:
    summary: eIF2α is a component of cytoplasmic stress granules, which form when translation is attenuated during stress. The evidence from HDA (homology-derived annotation) suggests stress granule localization may be conserved. However, more mechanistically, eIF2α is involved in translational control OF stress responses, not localization to stress granules itself.
    action: KEEP_AS_NON_CORE
    reason: eIF2α is phosphorylated during stress and this phosphorylation triggers translational attenuation and GCN4 upregulation. The association with stress granules is a secondary consequence of translational shutdown, not a primary function. The core function is "translation control in response to stress" rather than stress granule localization. This annotation can be retained as contextual but is not a core function of the protein. HDA evidence quality is lower than IDA/IBA.
    additional_reference_ids:
      - PMID:1739968
    supported_by:
      - reference_id: PMID:26777405
        supporting_text: "ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure."
- term:
    id: GO:1990856
    label: methionyl-initiator methionine tRNA binding
  evidence_type: IDA
  original_reference_id: PMID:16565414
  review:
    summary: Direct experimental evidence demonstrating eIF2α's specific binding to methionyl-initiator tRNA using a reconstituted yeast translation system. This is eIF2α's most direct and specific molecular interaction, critical for ternary complex formation and initiation.
    action: ACCEPT
    reason: This is eIF2α's core ligand-binding function. The methionyl-initiator tRNA is the only substrate that eIF2α efficiently binds in the GTP-bound state. This represents the fundamental molecular interaction that underlies eIF2α's role as a translation initiation factor. The paper demonstrates that initiator-specific tRNA identity elements are recognized by eIF2α. This is not just a binding activity but THE defining molecular interaction of the protein.
    supported_by:
      - reference_id: PMID:16565414
        supporting_text: "the initiator-specific A1:U72 base pair at the top of the acceptor stem is important for the binding of the eIF2.GTP.Met-tRNA(i) ternary complex to the 40S ribosomal subunit"
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IDA
  original_reference_id: PMID:14698289
  review:
    summary: Direct experimental evidence from thermodynamic characterization of eIF2 shows GTP-dependent binding interactions with methionyl-tRNA. GTP binding is the nucleotide-binding function but represents a mechanism for methionyl-tRNA recognition rather than a general GTPase activity. The relation between GTP binding and methionine moiety recognition is mechanistically key.
    action: ACCEPT
    reason: eIF2α is a GTPase that binds GTP and hydrolyzes it during the translation initiation cycle. The GTP binding is mechanistically important because GTP binding creates a conformational state that specifically recognizes the methionine moiety on initiator tRNA. This is not generic GTP binding but GTP-regulated methionyl-tRNA recognition. The term "GTP binding" is appropriate for this molecular interaction.
    supported_by:
      - reference_id: PMID:14698289
        supporting_text: "In its GTP-bound state the factor forms a positive interaction with the methionine moiety on Met-tRNA(i) that is disrupted when GTP is replaced with GDP"
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IDA
  original_reference_id: PMID:16246727
  review:
    summary: This is a duplicate GTP binding annotation from another mechanistic study demonstrating that phosphate (Pi) release from eIF2, not GTP hydrolysis itself, is the step controlled during start site selection. This provides complementary evidence that GTP binding/hydrolysis is central to the initiation mechanism.
    action: ACCEPT
    reason: Multiple IDA annotations of GTP binding from different mechanistic studies strengthen evidence. The second paper provides additional insight that Pi release (GTPase product release) rather than GTP hydrolysis per se is the rate-limiting step for start codon recognition. Both papers confirm GTP binding and GTPase activity are mechanistically central to eIF2α function.
    supported_by:
      - reference_id: PMID:16246727
        supporting_text: "Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site selection during eukaryotic translation initiation."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-SCE-9633480
  review:
    summary: Cytosol localization from Reactome curated pathway for GCN2 phosphorylation of eIF2α. TAS (Traced to Authoritative Source) indicates this comes from a high-quality curated database. This duplicates the IEA cytosol annotation already provided.
    action: ACCEPT
    reason: Multiple evidence types (IEA, TAS) for cytosol localization strengthen the annotation. The Reactome reference provides expert curation. eIF2α is a cytosolic protein essential for cytoplasmic translation initiation.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:11914276
  review:
    summary: Cytoplasm localization from yeast proteome subcellular localization study. Cytoplasm is a broader term than cytosol, referring to all non-nuclear cytoplasmic compartments. eIF2α is specifically a cytosolic protein.
    action: ACCEPT
    reason: While cytosol (GO:0005829) is more specific and already annotated, cytoplasm (GO:0005737) is broader and includes both cytosol and other cytoplasmic compartments. For a cytosolic translation factor, cytoplasm annotation is acceptable as non-redundant context, indicating eIF2α is found in the cytoplasmic compartment. HDA evidence is reasonable for established localization.
    supported_by:
      - reference_id: PMID:11914276
        supporting_text: "Subcellular localization of the yeast proteome."
- term:
    id: GO:0033290
    label: eukaryotic 48S preinitiation complex
  evidence_type: IDA
  original_reference_id: PMID:17242201
  review:
    summary: This is a duplicate of the IBA annotation for 48S preinitiation complex. IDA evidence from coupled release studies of translation factors confirms eIF2 association with the 48S complex during initiation.
    action: ACCEPT
    reason: Multiple evidence types (IBA, IDA) for 48S preinitiation complex membership strengthen the annotation. The IDA evidence from studies of eIF5B and eIF1A release demonstrates eIF2 is part of the functional 48S complex. This is a core structural annotation.
    supported_by:
      - reference_id: PMID:17242201
        supporting_text: "Coupled release of eukaryotic translation initiation factors 5B and 1A from 80S ribosomes following subunit joining."
- term:
    id: GO:0001731
    label: formation of translation preinitiation complex
  evidence_type: IDA
  original_reference_id: PMID:12008673
  review:
    summary: Direct experimental evidence from reconstituted yeast translation initiation system showing eIF2α is required for 43S complex formation. This biological process term describes eIF2α's mechanistic role in complex assembly.
    action: ACCEPT
    reason: eIF2α is absolutely essential for formation of the 43S preinitiation complex because it delivers the initiator tRNA that is the core cargo. The paper demonstrates reconstituted system dependence on eIF2 for complex assembly. This is a core process annotation showing eIF2α's mechanistic role.
    supported_by:
      - reference_id: PMID:12008673
        supporting_text: "Development and characterization of a reconstituted yeast translation initiation system"
- term:
    id: GO:0043614
    label: multi-eIF complex
  evidence_type: IDA
  original_reference_id: PMID:15838098
  review:
    summary: eIF2α is part of the multifactor complex (MFC) containing eIF1, eIF2, eIF3, eIF5, and initiator tRNA. This IDA evidence from yeast translational control studies confirms eIF2 association with other initiation factors in higher-order complex.
    action: ACCEPT
    reason: eIF2α is a structural and functional component of the multifactor complex that forms during translation initiation. This is documented in early yeast in vitro studies. The MFC is a physiologically important intermediate in initiation. This represents core complex membership.
    supported_by:
      - reference_id: PMID:15838098
        supporting_text: "Study of translational control of eukaryotic gene expression using yeast."
- term:
    id: GO:0005850
    label: eukaryotic translation initiation factor 2 complex
  evidence_type: IMP
  original_reference_id: PMID:2649894
  review:
    summary: This is a duplicate of the IBA and IPI annotations for eIF2 complex. The landmark paper identifying SUI2 as eIF2α provides foundational IMP (Inferred from Mutant Phenotype) evidence. Suppressor mutations in sui2 that suppress initiator codon mutations demonstrate eIF2α's essential role in initiation.
    action: ACCEPT
    reason: Multiple evidence types (IBA, IPI, IMP) for eIF2 complex membership provide comprehensive evidence. The original discovery paper uses mutant suppression analysis to establish SUI2 as the eIF2α gene, providing biological evidence of function. All three evidence types confirm this core annotation.
    supported_by:
      - reference_id: PMID:2649894
        supporting_text: "the sui2 suppressor gene encodes the alpha subunit of eIF-2"
- term:
    id: GO:0043614
    label: multi-eIF complex
  evidence_type: IDA
  original_reference_id: PMID:11018020
  review:
    summary: This is a duplicate of the IDA multi-eIF complex annotation from another study describing multifactor complex function and importance in translation initiation.
    action: ACCEPT
    reason: Multiple IDA annotations for the same structural term from different studies strengthen evidence. Both papers demonstrate eIF2 is part of the physiologically important multifactor complex with eIF1, eIF3, eIF5, and initiator tRNA.
    supported_by:
      - reference_id: PMID:11018020
        supporting_text: "A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo."
core_functions:
  - molecular_function:
      id: GO:0003743
      label: translation initiation factor activity
    substrates:
      - id: GO:1990856
        label: methionyl-initiator methionine tRNA binding
      - id: GO:0005525
        label: GTP binding
    description: |
      eIF2α is the catalytic subunit of the eIF2 GTPase complex that delivers formyl-Met-tRNAi
      to the 40S ribosomal subunit in a GTP-dependent manner. The conformational state imposed
      by GTP binding creates a recognition pocket for the methionine moiety of initiator tRNA,
      enabling specific discrimination from elongator methionine tRNA. Upon recognition of the
      cognate AUG start codon, GTP hydrolysis and phosphate release trigger release of the
      eIF2-GDP binary complex, which must be recycled by eIF2B to regenerate eIF2-GTP.
    locations:
      - id: GO:0005829
        label: cytosol
    in_complex:
      id: GO:0005850
      label: eukaryotic translation initiation factor 2 complex
    directly_involved_in:
      - id: GO:0006413
        label: translational initiation
  - molecular_function:
      id: GO:0003743
      label: translation initiation factor activity
    description: |
      eIF2α is the alpha subunit of the heterotrimeric eIF2 complex (alpha/beta/gamma subunits)
      that forms the molecular switch for translation control. eIF2α interactions with the beta
      subunit (SUI3) and gamma subunit (GCD1/GCD2) are essential for complex stability and
      function. Assembly is facilitated by the chaperone-like factor CDC123. eIF2α is a target
      for phosphorylation at Ser-52 by the kinases GCN2, HRI, and PKR during stress conditions,
      which inhibits the GEF activity of eIF2B and attenuates global translation while
      maintaining selective translation of stress response genes like GCN4.
    in_complex:
      id: GO:0005850
      label: eukaryotic translation initiation factor 2 complex
    locations:
      - id: GO:0005829
        label: cytosol
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11018020
  title: A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3,
    eIF5, and initiator tRNA(Met) is an important translation initiation intermediate
    in vivo.
  findings: []
- id: PMID:11805837
  title: Systematic identification of protein complexes in Saccharomyces cerevisiae
    by mass spectrometry.
  findings: []
- id: PMID:11914276
  title: Subcellular localization of the yeast proteome.
  findings: []
- id: PMID:12008673
  title: Development and characterization of a reconstituted yeast translation initiation
    system.
  findings: []
- id: PMID:14698289
  title: GTP-dependent recognition of the methionine moiety on initiator tRNA by translation
    factor eIF2.
  findings: []
- id: PMID:15838098
  title: Study of translational control of eukaryotic gene expression using yeast.
  findings: []
- id: PMID:16246727
  title: Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site
    selection during eukaryotic translation initiation.
  findings: []
- id: PMID:16429126
  title: Proteome survey reveals modularity of the yeast cell machinery.
  findings: []
- id: PMID:16554755
  title: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
  findings: []
- id: PMID:16565414
  title: Yeast initiator tRNA identity elements cooperate to influence multiple steps
    of translation initiation.
  findings: []
- id: PMID:17242201
  title: Coupled release of eukaryotic translation initiation factors 5B and 1A from
    80S ribosomes following subunit joining.
  findings: []
- id: PMID:18719252
  title: High-quality binary protein interaction map of the yeast interactome network.
  findings: []
- id: PMID:20485439
  title: eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation.
  findings: []
- id: PMID:23775072
  title: Translation initiation requires cell division cycle 123 (Cdc123) to facilitate
    biogenesis of the eukaryotic initiation factor 2 (eIF2).
  findings: []
- id: PMID:24852487
  title: eIF2B is a decameric guanine nucleotide exchange factor with a γ2ε2 tetrameric
    core.
  findings: []
- id: PMID:26211610
  title: Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp
    Protein with Unique Features.
  findings: []
- id: PMID:2649894
  title: Yeast translation initiation suppressor sui2 encodes the alpha subunit of
    eukaryotic initiation factor 2 and shares sequence identity with the human alpha
    subunit.
  findings: []
- id: PMID:26777405
  title: ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure.
  findings: []
- id: PMID:27107014
  title: An inter-species protein-protein interaction network across vast evolutionary
    distance.
  findings: []
- id: PMID:37507029
  title: Binding of human Cdc123 to eIF2γ.
  findings: []
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings: []
- id: PMID:8947054
  title: 'Ligand interactions with eukaryotic translation initiation factor 2: role
    of the gamma-subunit.'
  findings: []
- id: Reactome:R-SCE-9633480
  title: GCN2 phosphorylates SUI2
  findings: []

SUI2

Gene Description