SUI2

Existing Annotations Review

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

SGD

SGD gene description for SUI2 (yeast)

📚 Additional Documentation

Notes

📄 View Raw YAML

GO Term	Evidence	Action	Reason
GO:0003743 translation initiation factor activity	IBA GO_REF:0000033	ACCEPT	Summary: eIF2α is the non-catalytic regulatory (alpha) subunit of the heterotrimeric eIF2 complex; as part of the complex it delivers initiator Met-tRNAi to the 40S ribosomal subunit in a GTP-dependent manner (GTP binding and GTPase activity reside in the gamma subunit Gcd11/eIF2γ). This molecular function term accurately captures its role in translation initiation. IBA evidence through phylogenetic comparison is appropriate. Reason: eIF2α is fundamentally a translation initiation factor; it is the non-enzymatic regulatory subunit that contributes to the eIF2 trimer's function rather than possessing catalytic activity of its own. Its core function is contributing to delivery of 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. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000063907 · PTN000063907 SUPPORTS TRANSFER Current PTHR10602 PAINT retains this translation-initiation activity IBD at the node that includes Sui2/eIF2alpha; target SGD:S000003767 is valid experimental grounding, not circular support. 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 file:yeast/SUI2/SUI2-deep-research-falcon.md eIF2 binds GTP and initiator Met-tRNAi\(^Met\) to form the ternary complex (TC)**, which is required to deliver initiator tRNA to the 40S ribosomal subunit and assemble the 43S/48S preinitiation complex (PIC)
GO:0006413 translational initiation	IBA GO_REF:0000033	ACCEPT	Summary: eIF2α is required for the initiation phase of translation; as the non-catalytic regulatory subunit of the eIF2 trimer it contributes to delivery of the initiator Met-tRNAi via the eIF2 ternary complex and to start codon recognition (the GTPase activity that drives this cycle resides in the gamma subunit Gcd11/eIF2γ). This biological process annotation is appropriate and represents a core function. Reason: eIF2α is essential for translation initiation as a regulatory subunit of the eIF2 complex that contributes to the GTP-dependent delivery of initiator Met-tRNAi to the 40S ribosome via the ternary complex. It is non-catalytic (GTP binding and hydrolysis reside in the gamma subunit), but it is mechanistically essential for initiation rather than merely associated with it. IBA evidence is appropriate. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000063907 · PTN000063907 SUPPORTS TRANSFER Current PAINT places translational initiation on the conserved eIF2alpha family node and includes direct yeast SUI2 evidence among the descendant seeds. 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 file:yeast/SUI2/SUI2-deep-research-falcon.md In eukaryotic translation initiation, eIF2 binds GTP and initiator Met-tRNAi\(^Met\) to form the ternary complex (TC), which is required to deliver initiator tRNA to the 40S ribosomal subunit and assemble the 43S/48S preinitiation complex (PIC). In yeast, this TC-dependent step is a central determinant of initiation rate and start-site selection.
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. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000063908 · PTN000063908 SUPPORTS TRANSFER Current PAINT retains eIF2 complex membership at the eukaryotic eIF2alpha node, with SUI2 itself and vertebrate orthologs as experimentally grounded seeds. Supporting Evidence: PMID:2649894 the sui2 suppressor gene encodes the alpha subunit of eIF-2 file:yeast/SUI2/SUI2-deep-research-falcon.md SUI2 in Saccharomyces cerevisiae (S288c; ORF YJR007W) encodes the α subunit of eukaryotic translation initiation factor 2 (eIF2α), a core component of the heterotrimeric eIF2 complex (eIF2α/Sui2, eIF2β/Sui3, eIF2γ/Gcd11)
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. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000063908 · PTN000063908 SUPPORTS TRANSFER The current eukaryote-restricted PTHR10602 PAINT node carries the 48S preinitiation complex IBD and includes yeast SUI2 direct evidence. 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 file:yeast/SUI2/SUI2-deep-research-falcon.md It operates on the 40S subunit within 43S/48S preinitiation complexes during scanning and start codon recognition.
GO:0043022 ribosome binding	IBA GO_REF:0000033	ACCEPT	Summary: eIF2alpha makes direct 40S ribosomal contacts in the yeast preinitiation complex, including the R53 contact with 18S rRNA helix 23 in both open and closed PIC states. Reason: Ribosome binding is broad but true: eIF2alpha directly contacts the 40S subunit within the scanning and start-recognition preinitiation complex, and the Thakur 2020 structural/mechanistic analysis specifically maps residue R53 contacting rRNA helix 23. The current PTN000063907 IBD is still present in PTHR10602 PAINT and is compatible with the yeast PIC contact. This row therefore captures a direct ribosomal contact that is not replaced by the existing translation-initiation-factor or methionyl-initiator-tRNA-binding rows. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000063907 · PTN000063907 SUPPORTS TRANSFER Current PTHR10602 PAINT places the ribosome-binding IBD on the conserved eIF2alpha node, and target structural evidence supports direct Sui2/eIF2alpha contact with the 40S ribosomal subunit. Supporting Evidence: file:yeast/SUI2/SUI2-deep-research-falcon.md R53 contacts rRNA helix 23; Arg55/Arg57 contact mRNA context near the start site; unstructured N-terminal tail interacts with eIF1 in the open PIC and later with eIF5-CTD after AUG recognition
GO:0003676 nucleic acid binding	IEA GO_REF:0000002	TOO GENERAL	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. TOO_GENERAL rather than REMOVE: methionyl-initiator methionine tRNA binding, kept in this review, entails this term, so the claim is true but less informative.
GO:0003723 RNA binding	IEA GO_REF:0000120	TOO GENERAL	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. TOO_GENERAL rather than REMOVE: methionyl-initiator methionine tRNA binding, kept in this review, entails this term, so the claim is true but less informative.
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. Supporting Evidence: file:yeast/SUI2/SUI2-deep-research-falcon.md the mechanistic literature places Sui2/eIF2α functionally in the cytosolic translation initiation pathway
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...	REMOVE	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 (Gcd11) subunits, but the term "protein binding" is uninformative. Reason: GO:0005515 protein binding is uninformative about molecular function. Removing this annotation does not mean the reported interaction is false; eIF2alpha's stable subunit interactions are captured more informatively by the eukaryotic translation initiation factor 2 complex 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...	REMOVE	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 from a proteome-wide complex survey does not add a Sui2 molecular-function assertion beyond eIF2 complex membership and the mechanistic initiation annotations. Removal only rejects GO:0005515 as an uninformative GO term here, not the physical association. 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...	REMOVE	Summary: Protein binding from global landscape of yeast protein complexes study. Again, uninformative generic term for eIF2 complex membership. Reason: This high-throughput interaction supports eIF2 physical association, but GO:0005515 protein binding is too generic to convey Sui2's activity or complex membership. The eIF2 complex and translation-initiation annotations carry the functional content. 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...	REMOVE	Summary: Protein binding from high-quality binary protein interaction map. Generic annotation. Reason: The binary interactome result is not enough to make GO:0005515 an informative molecular-function annotation. Sui2 function is better represented by eIF2 complex membership and its translation-initiation factor activity. Supporting Evidence: PMID:18719252 demonstrating that high-throughput yeast two-hybrid (Y2H) screening provides high-quality binary interaction information
GO:0005515 protein binding	IPI PMID:20485439 eIF5 has GDI activity necessary for translational control by...	REMOVE	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 mechanistically important for eIF2 recycling and translational control, but GO:0005515 does not distinguish this regulatory contact from arbitrary protein interactions. It is better handled through eIF2 cycle and multi-eIF complex annotations than retained as generic protein binding. 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...	REMOVE	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 eIF2-eIF2B interaction is central to nucleotide exchange and stress control, but GO:0005515 protein binding obscures rather than captures that mechanism. No evidence-backed Sui2-specific MF replacement is needed because the reviewed eIF2 complex and GTP-dependent initiation annotations already describe the direct function. 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 ...	REMOVE	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 binding supports eIF2alpha-gamma assembly, but the Sui2 row still collapses an assembly-factor interaction to generic GO:0005515 protein binding. The eIF2 complex annotation captures the resulting core structure; the generic binding term should not be retained. 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 ...	REMOVE	Summary: Inter-species protein interaction network. Generic protein binding from computational/comparative analysis. Reason: Generic protein binding from an inter-species interaction survey provides little mechanistic information for Sui2. The curated complex and translation-initiation rows are the appropriate functional representation. 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.	REMOVE	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: Human Cdc123 binding to eIF2gamma is relevant background for eIF2 assembly but does not justify retaining a low-information SUI2 protein-binding annotation. Sui2's stable product is the heterotrimeric eIF2 complex, which is already captured directly. 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 ...	REMOVE	Summary: Social and structural architecture of yeast protein interactome. Generic proteome-wide interaction annotation. Reason: The proteome-wide interaction survey is not a specific molecular-function assertion for Sui2. GO:0005515 protein binding should be removed in favor of eIF2 complex membership and specific translation-initiation 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...	REMOVE	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 mechanistic eIF2 study supports the initiation cycle, but GO:0005515 protein binding is not the right representation of Sui2's role in the heterotrimer. The eIF2 complex and translational initiation annotations capture the functional result. 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 file:yeast/SUI2/SUI2-deep-research-falcon.md Beyond TC delivery, eIF2α contributes directly to start-codon selection fidelity during scanning. A high-quality yeast genetic/biochemical study built on cryo-EM PIC models shows that specific eIF2α residues contact rRNA and influence open/closed PIC conformations during scanning and AUG recognition.
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 Gcd11, the eIF2 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 HDA evidence directly places Sui2 in stress-granule proteomes. 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, but the high-throughput direct assay evidence can be retained as contextual localization evidence. Supporting Evidence: PMID:26777405 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. file:yeast/SUI2/SUI2-deep-research-falcon.md Its most prominent regulatory role is as the conserved substrate of Gcn2: Ser51 phosphorylation converts eIF2 into a potent functional inhibitor of eIF2B, decreasing TC availability and thereby globally repressing initiation while enabling selective translation programs such as GCN4 induction via uORF-mediated reinitiation control.
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 file:yeast/SUI2/SUI2-deep-research-falcon.md R53 contacts rRNA helix 23; Arg55/Arg57 contact mRNA context near the start site; unstructured N-terminal tail interacts with eIF1 in the open PIC and later with eIF5-CTD after AUG recognition
GO:0005525 GTP binding	IDA PMID:14698289 GTP-dependent recognition of the methionine moiety on initia...	ACCEPT	Summary: Direct experimental evidence (PMID:14698289) from thermodynamic characterization of the eIF2 holocomplex shows GTP-dependent recognition of the methionine moiety on initiator tRNA. The GOA annotation carries the contributes_to qualifier, which is biologically correct: GTP binding and hydrolysis are intrinsic to the eIF2 gamma subunit (Gcd11/eIF2γ), and Sui2/eIF2α only contributes to the complex's GTP-regulated state rather than acting as a GTPase itself. Reason: The GTP binding annotation is accepted with the GOA contributes_to qualifier. Falcon deep research clarifies that eIF2α/Sui2 is a non-enzymatic subunit and has no catalytic activity of its own; the nucleotide-binding/GTPase function resides in the gamma subunit (Gcd11/eIF2γ). The PMID:14698289 measurements are made on the assembled eIF2 ternary complex, where GTP binding creates a conformational state that specifically recognizes the methionine moiety on initiator tRNA. The annotation therefore correctly captures eIF2's GTP-dependent behavior as a complex, and the contributes_to qualifier appropriately scopes Sui2's role. (Prior reasoning that "eIF2α is a GTPase" was an over-statement and has been corrected.) 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 file:yeast/SUI2/SUI2-deep-research-falcon.md SUI2 (UniProt P20459) encodes yeast eIF2α, a non-enzymatic translation initiation factor whose primary molecular function is to contribute to formation and function of the eIF2·GTP·Met-tRNAi ternary complex
GO:0005525 GTP binding	IDA PMID:16246727 Pi release from eIF2, not GTP hydrolysis, is the step contro...	ACCEPT	Summary: This is a second IDA GTP binding annotation (contributes_to) from a mechanistic study demonstrating that phosphate (Pi) release from eIF2, not GTP hydrolysis itself, is the step controlled during start-site selection. It provides complementary evidence that the eIF2 complex's GTP binding/hydrolysis cycle is central to the initiation mechanism. Reason: Accepted with the GOA contributes_to qualifier. As with the PMID:14698289 GTP binding annotation, the nucleotide-binding/GTPase activity is a property of the eIF2 gamma subunit (Gcd11/eIF2γ), not of Sui2/eIF2α, which is non-enzymatic. This 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 GTP binding annotations describe behavior of the assembled eIF2 complex, and the contributes_to qualifier correctly scopes the alpha-subunit's role. Supporting Evidence: PMID:16246727 Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site selection during eukaryotic translation initiation. file:yeast/SUI2/SUI2-deep-research-falcon.md After start-codon recognition, eIF2 hydrolyzes GTP and leaves the ribosome in a GDP-bound state. Reactivation requires the guanine nucleotide exchange factor eIF2B, which catalyzes GDP→GTP exchange on eIF2.
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.