Existing Annotations Review

Core Functions

eIF2α is a non-enzymatic subunit of the heterotrimeric eIF2 complex; as part of the complex (whose GTP binding and GTPase activity reside in the gamma subunit Gcd11/eIF2γ), eIF2 delivers 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. eIF2α contributes directly to start-codon selection fidelity within the scanning 43S/48S PIC: its unstructured N-terminal tail interacts with eIF1 to stabilize the open/scanning state, and residues such as R53 contact rRNA helix 23. 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 (Gcd11) are essential for complex stability and function. Assembly is facilitated by the chaperone-like factor Cdc123. In yeast, eIF2α is a target for phosphorylation at Ser-52 (yeast UniProt numbering; the conserved cross-species Ser51 site) by the kinase Gcn2 in response to amino acid, carbon, or purine limitation (the orthologous mammalian kinases HRI/PKR/PERK are not present in budding yeast). This single-site phosphorylation converts eIF2 from an eIF2B substrate into an inhibitor of the eIF2B GEF, lowering ternary complex abundance to attenuate global translation while derepressing translation of stress-response genes such as GCN4 via uORF-mediated reinitiation control.

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

file:yeast/SUI2/SUI2-deep-research-falcon.md

Falcon deep research report on SUI2 (yeast eIF2alpha, UniProt P20459)

SUI2 (YJR007W) encodes the alpha subunit of the heterotrimeric eIF2 complex (eIF2alpha/Sui2, eIF2beta/Sui3, eIF2gamma/Gcd11); eIF2 binds GTP and initiator Met-tRNAi to form the ternary complex that delivers initiator tRNA to the 40S ribosome and assembles the 43S/48S preinitiation complex.

"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)"
eIF2alpha is non-enzymatic; its primary molecular function is to contribute to formation and function of the eIF2.GTP.Met-tRNAi ternary complex and to start-codon selection. GTP binding/GTPase activity reside in the gamma subunit.

"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"
After start-codon recognition eIF2 hydrolyzes GTP and leaves the ribosome in the GDP-bound state; reactivation requires the GEF eIF2B to catalyze GDP-to-GTP exchange, a cycle essential for continued rounds of initiation.

"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."
Phosphorylation of eIF2alpha at the conserved Ser51 site by the kinase Gcn2 converts eIF2 from an eIF2B substrate into an inhibitor of eIF2B, lowering eIF2-GTP and ternary complex abundance and decreasing general translation initiation.

"A conserved translational-control mechanism in yeast is **phosphorylation of eIF2α at Ser51** by the kinase **Gcn2**. This single-site phosphorylation changes eIF2 from an eIF2B substrate into an **inhibitor of eIF2B**, lowering eIF2-GTP and TC abundance and thereby decreasing general translation initiation."
In the general amino acid control (GAAC), amino acid limitation increases uncharged tRNAs that activate Gcn2 (via Gcn1/Gcn20), triggering Ser51 phosphorylation of eIF2alpha; this represses bulk initiation while derepressing GCN4 via uORF-mediated reinitiation control.

"In budding yeast, amino acid limitation increases **deacylated (uncharged) tRNAs**, which activate **Gcn2** (facilitated by **Gcn1/Gcn20**), causing **Ser51 phosphorylation of eIF2α**. This reduces TC abundance and globally represses initiation, while enabling selective translation of stress-response transcripts—classically **GCN4**, whose uORF architecture makes its translation inversely related to TC availability."
eIF2alpha comprises three domains - an N-terminal OB-fold, a central alpha-helical domain, and a C-terminal alpha/beta domain that contacts eIF2gamma; the regulatory Ser51 lies in a mobile loop within the OB-fold domain.

"A yeast-focused synthesis of translation mechanisms describes eIF2α as composed of **three domains**: an **N-terminal OB-fold**, a **central α-helical domain**, and a **C-terminal α/β domain** that contacts eIF2γ. The **regulatory Ser51** is located in a mobile loop within the OB-fold domain."
eIF2alpha contributes directly to start-codon selection fidelity: its unstructured N-terminal tail interacts with eIF1 to stabilize the open/scanning PIC and rearranges upon AUG recognition, and residue R53 contacts rRNA helix 23 while Arg55/Arg57 contact mRNA context near the start site.

"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"
The yeast Sui2 phosphosite Ser52 (UniProt numbering) corresponds to the conserved cross-species Ser51 regulatory residue used in most antibodies and studies.

"Sui2 phosphosite is adjacent to the canonical Ser51 numbering convention used in many studies/antibodies"
Phosphorylated eIF2 binds eIF2B with ~10-fold higher affinity than unphosphorylated eIF2 (Kd 3.5 nM vs 32.2 nM), supporting the model in which eIF2alpha-P sequesters and inhibits the eIF2B GEF.

"phosphorylated eIF2 was reported (in the paper’s cited measurement) to have ~10-fold higher affinity for eIF2B than unphosphorylated eIF2 (Kd **3.5 nM vs 32.2 nM**), supporting the sequestration/inhibition model."
The Gcn2-eIF2alpha Ser51 switch operates in stress responses beyond classic amino acid starvation: a phospho-dead sui2-S51A mutant is acid-sensitive, and the pathway limits initiation under severe iron deficiency.

"a phosphorylation-defective **sui2-S51A** mutant is acid-sensitive, implicating the eIF2α phosphorylation switch in adaptation."

Deep Research

Falcon

(SUI2-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 28 citations 1 artifacts 2026-05-30T17:55:08.175739

Edison artifact artifact-00 (text/markdown)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive Research Report: Saccharomyces cerevisiae SUI2 (UniProt P20459; eIF2α)

1) Target verification and gene/protein identity (mandatory disambiguation)

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). This matches the UniProt description for P20459 (eukaryotic translation initiation factor 2 subunit alpha). (dever2016mechanismandregulation pages 6-7)

2) Key concepts and definitions (current understanding)

2.1 eIF2 and the ternary complex (TC)

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. (dever2016mechanismandregulation pages 6-7)

2.2 The eIF2 cycle and the role of eIF2B (GEF)

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. This recycling is essential for continued rounds of initiation. (adomavicius2019thestructuralbasis pages 1-2)

2.3 Central regulatory switch: Ser51 phosphorylation of Sui2/eIF2α

A conserved translational-control mechanism in yeast is phosphorylation of eIF2α at Ser51 by the kinase Gcn2. This single-site phosphorylation changes eIF2 from an eIF2B substrate into an inhibitor of eIF2B, lowering eIF2-GTP and TC abundance and thereby decreasing general translation initiation. (dever2016mechanismandregulation pages 6-7, cherkasova2003translationalcontrolby pages 1-2, dever2016mechanismandregulation pages 27-28)

3) Molecular function of Sui2/eIF2α: precise mechanistic roles

3.1 Core function in initiation and start-codon selection

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. (thakur2020eif2αinteractionswith pages 12-13)

Key interaction concepts supported by the yeast PIC model:
- The unstructured N-terminal tail (NTT) of eIF2α interacts with eIF1 to stabilize the open/scanning PIC; upon AUG recognition, rearrangements disrupt this interaction and alter eIF2α contacts (e.g., with eIF5 domains), contributing to commitment to initiation. (thakur2020eif2αinteractionswith pages 2-2)
- Residue R53 of eIF2α contacts rRNA helix 23 in both open and closed py48S PIC states; an eIF2α mutation that reduces TC loading can derepress GCN4 translation even in gcn2Δ backgrounds by allowing bypass of inhibitory uORFs (mechanistic coupling of TC loading kinetics and uORF-controlled reinitiation). (thakur2020eif2αinteractionswith pages 12-13)

3.2 Structural/domain organization (linking UniProt domain expectations to literature)

A yeast-focused synthesis of translation mechanisms describes eIF2α as composed of three domains: an N-terminal OB-fold, a central α-helical domain, and a C-terminal α/β domain that contacts eIF2γ. The regulatory Ser51 is located in a mobile loop within the OB-fold domain. (dever2016mechanismandregulation pages 6-7)

4) Pathways and regulation involving SUI2/eIF2α in yeast

4.1 General amino acid control (GAAC) / ISR-like translational reprogramming

In budding yeast, amino acid limitation increases deacylated (uncharged) tRNAs, which activate Gcn2 (facilitated by Gcn1/Gcn20), causing Ser51 phosphorylation of eIF2α. This reduces TC abundance and globally represses initiation, while enabling selective translation of stress-response transcripts—classically GCN4, whose uORF architecture makes its translation inversely related to TC availability. (dever2016mechanismandregulation pages 27-28, romero2020globaltranslationalrepression pages 1-2)

A mechanistic description of the uORF-based control emphasizes:
- Under nutrient-replete conditions, high TC allows rapid reacquisition of TC by scanning 40S subunits after translating uORF1, promoting reinitiation at inhibitory uORFs and repression of the GCN4 ORF.
- Under starvation, eIF2α phosphorylation reduces TC, delaying reacquisition and enabling 40S subunits to bypass inhibitory uORFs and reinitiate at the GCN4 start codon. (dever2016mechanismandregulation pages 27-28)

4.2 Cross-talk with TOR/Tap42 nutrient signaling

TOR inhibition by rapamycin stimulates eIF2α Ser51 phosphorylation by Gcn2 and induces GCN4 translation; this response involves changes in Gcn2 regulatory phosphorylation (e.g., Ser577) and requires TAP42 and type-2A-related phosphatases, demonstrating cross-talk between TOR signaling and the Gcn2–eIF2α translational-control axis. (cherkasova2003translationalcontrolby pages 1-2)

4.3 Snf1 (yeast AMPK) and phosphatase control of eIF2α-P levels

Snf1 promotes eIF2α phosphorylation through two separable mechanisms:
- During histidine starvation of glucose-grown cells, Snf1 promotes Gcn2 activity (including activation-loop autophosphorylation on Gcn2) leading to higher eIF2α-P.
- Under some carbon-source conditions (e.g., galactose), Snf1 promotes eIF2α phosphorylation by inhibiting phosphatases Glc7 (PP1) and Sit4 (PP2A-like); both phosphatases physically interact with eIF2α, supporting direct dephosphorylation. (cherkasova2010snf1promotesphosphorylation pages 1-2)

5) Cellular localization (where Sui2 functions)

Direct localization imaging for Sui2 was not present in the retrieved corpus; however, the mechanistic literature places Sui2/eIF2α functionally in the cytosolic translation initiation pathway:
- It operates on the 40S subunit within 43S/48S preinitiation complexes during scanning and start codon recognition. (thakur2020eif2αinteractionswith pages 2-2, thakur2020eif2αinteractionswith pages 12-13)
- It participates in the cytosolic eIF2↔eIF2B nucleotide exchange cycle controlling TC levels. (adomavicius2019thestructuralbasis pages 1-2)

6) Recent developments and latest research (prioritizing 2023–2024 where possible)

Tool-based retrieval yielded limited 2023–2024 yeast Sui2-centric primary literature in the available corpus. The most relevant “recent” mechanistic advances available here are therefore anchored by:
- Cryo-EM structural mechanism explaining how phosphorylated versus unphosphorylated eIF2 engages eIF2B, with the conclusion that higher affinity of eIF2αP for eIF2B drives translational control; the paper also provides quantitative affinity values (Kd 3.5 nM phosphorylated vs 32.2 nM unphosphorylated in their cited measurements) and notes that partial phosphorylation can be sufficient because eIF2B is less abundant than eIF2. Publication date: May 2019; URL: https://doi.org/10.1038/s41467-019-10167-3. (adomavicius2019thestructuralbasis pages 1-2)
- Systems phosphoproteomics expanding the Gcn2-controlled network while retaining eIF2α phosphorylation dependence of GCN4 translational induction. Publication date: May 2021; URL: https://doi.org/10.1016/j.molcel.2021.02.037. (dokladal2021globalphosphoproteomicspinpoints pages 4-6)

Given the user request, this should be treated as an evidence-limited section rather than an assertion that no 2023–2024 work exists.

7) Current applications and real-world implementations (research and applied contexts)

Sui2/eIF2α and its Ser51 phosphorylation are widely used as operational readouts of nutrient/stress-regulated translational control in yeast:
- Phospho-specific immunoblotting against eIF2α phosphorylated at Ser51 is used to quantify pathway activation (e.g., after rapamycin, amino acid stress, or other perturbations). (cherkasova2003translationalcontrolby pages 1-2)
- GCN4-lacZ reporter derepression assays are used as sensitive functional tests for translation initiation factor activity and for dependence on eIF2α phosphorylation. (dokladal2021globalphosphoproteomicspinpoints pages 4-6)
- Polysome profiling provides a global measure of translation initiation changes and is used alongside pathway mutants; in a Gcn2-centered phosphoproteomics study, specific phosphomutants in the upstream activator Gcn20 produced measurable changes in polysome:monosome (P:M) ratios under rapamycin (−7.6% or +8.6% changes in specific mutants/conditions). (dokladal2021globalphosphoproteomicspinpoints pages 4-6)

Applied/physiological contexts in yeast supported by the retrieved corpus include:
- Intracellular acid stress tolerance, where a phosphorylation-defective sui2-S51A mutant is acid-sensitive, implicating the eIF2α phosphorylation switch in adaptation. (hueso2012anovelrole pages 1-2)
- Iron deficiency, where the Gcn2/eIF2α pathway limits translation initiation during severe iron limitation, consistent with global translational repression as a stress response. (romero2020globaltranslationalrepression pages 1-2)

8) Expert opinions and authoritative synthesis

An authoritative yeast translation review integrates genetic, biochemical, and structural evidence to position Sui2/eIF2α as both (i) a core TC component for initiation and (ii) a conserved translational-control node whose Ser51 phosphorylation regulates global initiation and selective translation (e.g., GCN4) through TC availability. Publication date: May 2016; URL: https://doi.org/10.1534/genetics.115.186221. (dever2016mechanismandregulation pages 6-7, dever2016mechanismandregulation pages 27-28)

9) Key statistics and quantitative data extracted from recent/representative studies

In yeast cryo-EM/biochemistry-based analysis of eIF2–eIF2B regulation, phosphorylated eIF2 was reported (in the paper’s cited measurement) to have ~10-fold higher affinity for eIF2B than unphosphorylated eIF2 (Kd 3.5 nM vs 32.2 nM), supporting the sequestration/inhibition model. (adomavicius2019thestructuralbasis pages 1-2)
In a quantitative phosphoproteomics-driven study of Gcn2 signaling, mutation of a Gcn2 target site in eIF2β (Sui3S80A) reduced stress-induced derepression of a GCN4-LacZ reporter by >58% (rapamycin) and >38% (3-AT), indicating that non-eIF2α targets can modulate the output of the same translational program. (dokladal2021globalphosphoproteomicspinpoints pages 4-6)
In the same study, polysome profiling showed modest but measurable changes in translation initiation, with specified phosphomutants producing 10.6% and 7.6% lower P:M ratios or 8.6% higher P:M ratio under defined rapamycin conditions. (dokladal2021globalphosphoproteomicspinpoints pages 4-6)

10) Summary functional annotation (narrative)

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 and to participate directly in start-codon selection within the 43S/48S PIC through defined interactions with rRNA/mRNA and other initiation factors. (dever2016mechanismandregulation pages 6-7, thakur2020eif2αinteractionswith pages 2-2, thakur2020eif2αinteractionswith pages 12-13)

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. This pathway is integrated with broader nutrient signaling networks including TOR/Tap42 phosphatase regulation and Snf1-mediated control of kinase/phosphatase activities. (cherkasova2003translationalcontrolby pages 1-2, cherkasova2010snf1promotesphosphorylation pages 1-2, dever2016mechanismandregulation pages 27-28)

Evidence-synthesis table

Aspect: identity/complex	Core molecular function	Key regulation/PTMs	Pathway context	Structural features/domains/residues	Representative evidence/assays	Key references with year and URL
SUI2 encodes the α subunit of heterotrimeric eIF2 in S. cerevisiae; partner subunits are Sui3/eIF2β and Gcd11/eIF2γ (dever2016mechanismandregulation pages 6-7)	eIF2 binds GTP and Met-tRNAi(^Met) to form the ternary complex (TC), delivering initiator tRNA to the 40S ribosome for 43S/48S preinitiation-complex assembly and start-codon recognition (dever2016mechanismandregulation pages 6-7)	Phosphorylation of eIF2α at conserved Ser51 by Gcn2 inhibits TC formation indirectly by converting eIF2 into an inhibitor of eIF2B-mediated GDP→GTP exchange (dever2016mechanismandregulation pages 6-7, cherkasova2003translationalcontrolby pages 1-2, dever2016mechanismandregulation pages 27-28)	Central node in translation initiation and the yeast general amino acid control / ISR-like stress response; reduced TC selectively derepresses GCN4 translation while lowering global initiation (dever2016mechanismandregulation pages 27-28)	eIF2α comprises an N-terminal OB-fold, a central α-helical domain, and a C-terminal α/β domain that contacts eIF2γ; Ser51 lies in a mobile loop in the OB-fold (dever2016mechanismandregulation pages 6-7)	Genetic suppressor analysis (Sui(^-) mutants), TC-binding/48S studies, cryo-EM-informed models, reporter assays for GCN4 control (dever2016mechanismandregulation pages 6-7, dever2016mechanismandregulation pages 27-28, adomavicius2019thestructuralbasis pages 1-2)	Dever et al., 2016, Genetics, https://doi.org/10.1534/genetics.115.186221; Adomavicius et al., 2019, Nat Commun, https://doi.org/10.1038/s41467-019-10167-3
eIF2α/Sui2 acts directly within the scanning preinitiation complex (thakur2020eif2αinteractionswith pages 2-2, thakur2020eif2αinteractionswith pages 12-13)	Helps stabilize scanning/open and start-recognition/closed states of the PIC; contributes to accuracy of AUG selection versus near-cognate codons such as UUG (thakur2020eif2αinteractionswith pages 12-13, thakur2020eif2αinteractionswith pages 2-2, thakur2020eif2αinteractionswith pages 7-8)	No catalytic activity of its own; function is regulated by phosphorylation state and by residue-specific interactions with mRNA/rRNA/eIF1/eIF5 (thakur2020eif2αinteractionswith pages 2-2, thakur2020eif2αinteractionswith pages 12-13)	Part of the eIF2 cycle linking TC loading, scanning, start-codon recognition, and factor recycling by eIF2B/eIF5 (adomavicius2019thestructuralbasis pages 1-2, dever2016mechanismandregulation pages 27-28)	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 (thakur2020eif2αinteractionswith pages 2-2, thakur2020eif2αinteractionswith pages 12-13)	HIS4-lacZ UUG:AUG reporters, growth phenotypes, plasmid-shuffle SUI2 alleles, β-gal assays, western blots, TC dissociation/recruitment measurements (thakur2020eif2αinteractionswith pages 7-8, thakur2020eif2αinteractionswith pages 5-6, thakur2020eif2αinteractionswith pages 12-13)	Thakur et al., 2020, Nucleic Acids Res, https://doi.org/10.1093/nar/gkaa761
eIF2α is the canonical substrate of yeast Gcn2 kinase under amino acid stress and other nutrient stresses (cherkasova2010snf1promotesphosphorylation pages 1-2, romero2020globaltranslationalrepression pages 1-2)	When phosphorylated, lowers available TC so scanning 40S subunits reacquire TC more slowly, enabling bypass of inhibitory uORFs in GCN4 leader and translation of GCN4 ORF (dever2016mechanismandregulation pages 27-28)	Ser51 phosphorylation is promoted by uncharged tRNAs via Gcn1/Gcn20 and can be influenced upstream by TOR/Tap42, Snf1, and phosphatases Glc7/Sit4 acting on the pathway (cherkasova2010snf1promotesphosphorylation pages 1-2, cherkasova2003translationalcontrolby pages 1-2, romero2020globaltranslationalrepression pages 1-2)	Integrates amino acid starvation, TOR inhibition/rapamycin response, iron deficiency, and intracellular acid stress into translational control (cherkasova2003translationalcontrolby pages 1-2, romero2020globaltranslationalrepression pages 1-2, hueso2012anovelrole pages 1-2)	Ser51 is the key phospho-acceptor residue; phosphorylation increases affinity of eIF2 for eIF2B, explaining inhibitory sequestration of the GEF (adomavicius2019thestructuralbasis pages 1-2, cherkasova2003translationalcontrolby pages 1-2)	Phospho-specific western blots, GCN4-lacZ derepression assays, polysome profiling, toeprinting, genetic epistasis with gcn2Δ/gcn1Δ and S51A mutants (dever2016mechanismandregulation pages 27-28, dokladal2021globalphosphoproteomicspinpoints pages 4-6, cherkasova2003translationalcontrolby pages 1-2)	Cherkasova & Hinnebusch, 2003, Genes Dev, https://doi.org/10.1101/gad.1069003; Romero et al., 2020, Sci Rep, https://doi.org/10.1038/s41598-019-57132-0
SUI2 participates in stress-adaptive translational control beyond classic amino acid starvation (hueso2012anovelrole pages 1-2, romero2020globaltranslationalrepression pages 1-2)	Supports selective translation programs that help cells adapt to nutrient and physicochemical stress while globally repressing bulk translation (hueso2012anovelrole pages 1-2, romero2020globaltranslationalrepression pages 1-2)	S51A phospho-dead Sui2 abolishes this regulatory switch in tested stress settings (hueso2012anovelrole pages 1-2, uppala2018phosphorylationoftranslation pages 9-12)	Shown for intracellular acid stress and iron deficiency, highlighting broad stress responsiveness of the Gcn2–eIF2α axis in yeast (hueso2012anovelrole pages 1-2, romero2020globaltranslationalrepression pages 1-2)	Same conserved Ser51-centered regulatory loop underlies distinct stress outputs (hueso2012anovelrole pages 1-2, uppala2018phosphorylationoftranslation pages 9-12)	Acid-stress growth phenotyping of sui2-S51A; iron-starvation analyses of global translation initiation dependence on Gcn2/eIF2α pathway (hueso2012anovelrole pages 1-2, romero2020globaltranslationalrepression pages 1-2)	Hueso et al., 2012, Biochem J, https://doi.org/10.1042/BJ20111264; Uppala et al., 2018, FEBS Lett, https://doi.org/10.1002/1873-3468.13214
Recent systems-level work extends the eIF2α-centered network to additional Gcn2 targets while retaining Sui2/eIF2α phosphorylation as the core output (dokladal2021globalphosphoproteomicspinpoints pages 4-6)	Confirms eIF2α phosphorylation-dependent derepression of GCN4 and identifies cooperating translational regulators (e.g., Sui3/eIF2β, Gcn20) (dokladal2021globalphosphoproteomicspinpoints pages 4-6)	In 2021 phosphoproteomics, Sui2-Ser52, Sui3-Ser80, and Gcn20 Thr94/Ser95 were robust Gcn2-dependent sites in rapamycin-treated or leucine-starved cells (dokladal2021globalphosphoproteomicspinpoints pages 4-6)	Places SUI2 within a broader Gcn2-regulated phospho-network affecting translation initiation under TOR inhibition and amino acid stress (dokladal2021globalphosphoproteomicspinpoints pages 4-6)	Sui2 phosphosite is adjacent to the canonical Ser51 numbering convention used in many studies/antibodies; evidence supports conserved regulatory-site assignment in yeast datasets (dokladal2021globalphosphoproteomicspinpoints pages 4-6, romero2020globaltranslationalrepression pages 1-2)	Quantitative phosphoproteomics, in vitro kinase assays, GCN4-lacZ reporter derepression, and polysome P:M measurements (e.g., Gcn20 phosphomutants changing P:M ratios by −10.6%, −7.6%, or +8.6% in specified conditions) (dokladal2021globalphosphoproteomicspinpoints pages 4-6)	Dokládal et al., 2021, Molecular Cell, https://doi.org/10.1016/j.molcel.2021.02.037

Table: This table compactly summarizes the verified identity, molecular function, regulation, structural features, pathway roles, and supporting evidence for yeast SUI2/eIF2α (UniProt P20459). It is useful as a citation-ready functional annotation artifact grounded only in the gathered evidence and context IDs.

References

(dever2016mechanismandregulation pages 6-7): TE Dever, TG Kinzy, and GD Pavitt. Mechanism and regulation of protein synthesis in saccharomyces cerevisiae. Genetics, 203:107-65, May 2016. URL: https://doi.org/10.1534/genetics.115.186221, doi:10.1534/genetics.115.186221. This article has 207 citations and is from a domain leading peer-reviewed journal.
(adomavicius2019thestructuralbasis pages 1-2): Tomas Adomavicius, Margherita Guaita, Yu Zhou, Martin D. Jennings, Zakia Latif, Alan M. Roseman, and Graham D. Pavitt. The structural basis of translational control by eif2 phosphorylation. Nature Communications, May 2019. URL: https://doi.org/10.1038/s41467-019-10167-3, doi:10.1038/s41467-019-10167-3. This article has 223 citations and is from a highest quality peer-reviewed journal.
(cherkasova2003translationalcontrolby pages 1-2): Vera A. Cherkasova and Alan G. Hinnebusch. Translational control by tor and tap42 through dephosphorylation of eif2alpha kinase gcn2. Genes & development, 17 7:859-72, Apr 2003. URL: https://doi.org/10.1101/gad.1069003, doi:10.1101/gad.1069003. This article has 393 citations and is from a highest quality peer-reviewed journal.
(dever2016mechanismandregulation pages 27-28): TE Dever, TG Kinzy, and GD Pavitt. Mechanism and regulation of protein synthesis in saccharomyces cerevisiae. Genetics, 203:107-65, May 2016. URL: https://doi.org/10.1534/genetics.115.186221, doi:10.1534/genetics.115.186221. This article has 207 citations and is from a domain leading peer-reviewed journal.
(thakur2020eif2αinteractionswith pages 12-13): Anil Thakur, Swati Gaikwad, Anil K Vijjamarri, and Alan G Hinnebusch. Eif2α interactions with mrna control accurate start codon selection by the translation preinitiation complex. Nucleic acids research, 48:10280-10296, Sep 2020. URL: https://doi.org/10.1093/nar/gkaa761, doi:10.1093/nar/gkaa761. This article has 27 citations and is from a highest quality peer-reviewed journal.
(thakur2020eif2αinteractionswith pages 2-2): Anil Thakur, Swati Gaikwad, Anil K Vijjamarri, and Alan G Hinnebusch. Eif2α interactions with mrna control accurate start codon selection by the translation preinitiation complex. Nucleic acids research, 48:10280-10296, Sep 2020. URL: https://doi.org/10.1093/nar/gkaa761, doi:10.1093/nar/gkaa761. This article has 27 citations and is from a highest quality peer-reviewed journal.
(romero2020globaltranslationalrepression pages 1-2): Antonia María Romero, Lucía Ramos-Alonso, Paula Alepuz, Sergi Puig, and María Teresa Martínez-Pastor. Global translational repression induced by iron deficiency in yeast depends on the gcn2/eif2α pathway. Scientific Reports, Jan 2020. URL: https://doi.org/10.1038/s41598-019-57132-0, doi:10.1038/s41598-019-57132-0. This article has 45 citations and is from a peer-reviewed journal.
(cherkasova2010snf1promotesphosphorylation pages 1-2): Vera Cherkasova, Hongfang Qiu, and Alan G. Hinnebusch. Snf1 promotes phosphorylation of the α subunit of eukaryotic translation initiation factor 2 by activating gcn2 and inhibiting phosphatases glc7 and sit4. Jun 2010. URL: https://doi.org/10.1128/mcb.00183-10, doi:10.1128/mcb.00183-10. This article has 75 citations and is from a domain leading peer-reviewed journal.
(dokladal2021globalphosphoproteomicspinpoints pages 4-6): Ladislav Dokládal, Michael Stumpe, Benjamin Pillet, Zehan Hu, Guillermo Miguel Garcia Osuna, Dieter Kressler, Jörn Dengjel, and Claudio De Virgilio. Global phosphoproteomics pinpoints uncharted gcn2-mediated mechanisms of translational control. Molecular Cell, 81:1879-1889.e6, May 2021. URL: https://doi.org/10.1016/j.molcel.2021.02.037, doi:10.1016/j.molcel.2021.02.037. This article has 40 citations and is from a highest quality peer-reviewed journal.
(hueso2012anovelrole pages 1-2): Guillem Hueso, Rafael Aparicio-Sanchis, Consuelo Montesinos, Silvia Lorenz, José R. Murguía, and Ramón Serrano. A novel role for protein kinase gcn2 in yeast tolerance to intracellular acid stress. Biochemical Journal, 441(1):255-264, Dec 2012. URL: https://doi.org/10.1042/bj20111264, doi:10.1042/bj20111264. This article has 62 citations and is from a domain leading peer-reviewed journal.
(thakur2020eif2αinteractionswith pages 7-8): Anil Thakur, Swati Gaikwad, Anil K Vijjamarri, and Alan G Hinnebusch. Eif2α interactions with mrna control accurate start codon selection by the translation preinitiation complex. Nucleic acids research, 48:10280-10296, Sep 2020. URL: https://doi.org/10.1093/nar/gkaa761, doi:10.1093/nar/gkaa761. This article has 27 citations and is from a highest quality peer-reviewed journal.
(thakur2020eif2αinteractionswith pages 5-6): Anil Thakur, Swati Gaikwad, Anil K Vijjamarri, and Alan G Hinnebusch. Eif2α interactions with mrna control accurate start codon selection by the translation preinitiation complex. Nucleic acids research, 48:10280-10296, Sep 2020. URL: https://doi.org/10.1093/nar/gkaa761, doi:10.1093/nar/gkaa761. This article has 27 citations and is from a highest quality peer-reviewed journal.
(uppala2018phosphorylationoftranslation pages 9-12): Jagadeesh Kumar Uppala, Chandrima Ghosh, Leena Sathe, and Madhusudan Dey. Phosphorylation of translation initiation factor eif2α at ser51 depends on site‐ and context‐specific information. FEBS Letters, 592:3116-3125, Sep 2018. URL: https://doi.org/10.1002/1873-3468.13214, doi:10.1002/1873-3468.13214. This article has 22 citations and is from a peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

dever2016mechanismandregulation pages 6-7
adomavicius2019thestructuralbasis pages 1-2
dever2016mechanismandregulation pages 27-28
cherkasova2003translationalcontrolby pages 1-2
dokladal2021globalphosphoproteomicspinpoints pages 4-6
hueso2012anovelrole pages 1-2
romero2020globaltranslationalrepression pages 1-2
uppala2018phosphorylationoftranslation pages 9-12
https://doi.org/10.1038/s41467-019-10167-3.
https://doi.org/10.1016/j.molcel.2021.02.037.
https://doi.org/10.1534/genetics.115.186221.
https://doi.org/10.1534/genetics.115.186221;
https://doi.org/10.1038/s41467-019-10167-3
https://doi.org/10.1093/nar/gkaa761
https://doi.org/10.1101/gad.1069003;
https://doi.org/10.1038/s41598-019-57132-0
https://doi.org/10.1042/BJ20111264;
https://doi.org/10.1002/1873-3468.13214
https://doi.org/10.1016/j.molcel.2021.02.037
https://doi.org/10.1534/genetics.115.186221,
https://doi.org/10.1038/s41467-019-10167-3,
https://doi.org/10.1101/gad.1069003,
https://doi.org/10.1093/nar/gkaa761,
https://doi.org/10.1038/s41598-019-57132-0,
https://doi.org/10.1128/mcb.00183-10,
https://doi.org/10.1016/j.molcel.2021.02.037,
https://doi.org/10.1042/bj20111264,
https://doi.org/10.1002/1873-3468.13214,

📚 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/Sui2, eIF2β/Sui3, eIF2γ/Gcd11). eIF2α
  is itself a non-enzymatic subunit; GTP binding and GTPase activity reside in the gamma
  subunit (Gcd11/eIF2γ). As part of the holocomplex, eIF2 plays a central role in
  translation initiation by binding GTP and initiator Met-tRNAi to form the ternary
  complex (TC), which delivers initiator tRNA to the 40S ribosomal subunit and assembles
  the 43S/48S preinitiation complex. eIF2α contributes directly to start-codon selection
  fidelity during scanning: its unstructured N-terminal tail interacts with eIF1 to
  stabilize the open/scanning PIC, and residue R53 contacts rRNA helix 23 in both open and
  closed states. Upon cognate AUG recognition, GTP hydrolysis and phosphate release trigger
  release of the eIF2-GDP binary complex, which is recycled by the GEF eIF2B. eIF2α is
  phosphorylated at Ser-52 (yeast UniProt numbering; the conserved cross-species Ser51
  site) by the kinase Gcn2 during nutrient/stress conditions; this single-site
  phosphorylation converts eIF2 from an eIF2B substrate into an inhibitor of eIF2B,
  lowering TC abundance to attenuate global translation while derepressing GCN4 translation
  via uORF-mediated reinitiation control. This makes SUI2 a critical node in the general
  amino acid control (GAAC) / integrated stress response.
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 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.
    action: ACCEPT
    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.
    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"
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          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)
- term:
    id: GO:0006413
    label: translational initiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    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"
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          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.
- 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"
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          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)
- 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"
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          It operates on the **40S subunit within 43S/48S preinitiation complexes** during scanning and start codon recognition.
- 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
    supported_by:
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          The **unstructured N-terminal tail (NTT)** of eIF2α interacts with **eIF1** to stabilize the open/scanning PIC; upon AUG recognition, rearrangements disrupt this interaction and alter eIF2α contacts (e.g., with eIF5 domains), contributing to commitment to initiation.
- 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.
    supported_by:
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          the mechanistic literature places Sui2/eIF2α functionally in the **cytosolic translation initiation pathway**
- 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"
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          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.
- 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."
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          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.
- 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"
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          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
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IDA
  original_reference_id: PMID:14698289
  qualifier: contributes_to
  review:
    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.
    action: ACCEPT
    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.)
    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"
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          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
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IDA
  original_reference_id: PMID:16246727
  qualifier: contributes_to
  review:
    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.
    action: ACCEPT
    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.
    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."
      - reference_id: file:yeast/SUI2/SUI2-deep-research-falcon.md
        supporting_text: |-
          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.
- 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 a non-enzymatic subunit of the heterotrimeric eIF2 complex; as part of the
      complex (whose GTP binding and GTPase activity reside in the gamma subunit Gcd11/eIF2γ),
      eIF2 delivers 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. eIF2α contributes directly to start-codon selection fidelity within the
      scanning 43S/48S PIC: its unstructured N-terminal tail interacts with eIF1 to stabilize
      the open/scanning state, and residues such as R53 contact rRNA helix 23. 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 (Gcd11) are essential for complex stability and
      function. Assembly is facilitated by the chaperone-like factor Cdc123. In yeast, eIF2α is a
      target for phosphorylation at Ser-52 (yeast UniProt numbering; the conserved cross-species
      Ser51 site) by the kinase Gcn2 in response to amino acid, carbon, or purine limitation
      (the orthologous mammalian kinases HRI/PKR/PERK are not present in budding yeast). This
      single-site phosphorylation converts eIF2 from an eIF2B substrate into an inhibitor of the
      eIF2B GEF, lowering ternary complex abundance to attenuate global translation while
      derepressing translation of stress-response genes such as GCN4 via uORF-mediated
      reinitiation control.
    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: []
- id: file:yeast/SUI2/SUI2-deep-research-falcon.md
  title: Falcon deep research report on SUI2 (yeast eIF2alpha, UniProt P20459)
  findings:
  - statement: |
      SUI2 (YJR007W) encodes the alpha subunit of the heterotrimeric eIF2 complex
      (eIF2alpha/Sui2, eIF2beta/Sui3, eIF2gamma/Gcd11); eIF2 binds GTP and initiator
      Met-tRNAi to form the ternary complex that delivers initiator tRNA to the 40S
      ribosome and assembles the 43S/48S preinitiation complex.
    supporting_text: |-
      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)
    reference_section_type: OTHER
  - statement: |
      eIF2alpha is non-enzymatic; its primary molecular function is to contribute to
      formation and function of the eIF2.GTP.Met-tRNAi ternary complex and to start-codon
      selection. GTP binding/GTPase activity reside in the gamma subunit.
    supporting_text: |-
      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
    reference_section_type: OTHER
  - statement: |
      After start-codon recognition eIF2 hydrolyzes GTP and leaves the ribosome in the
      GDP-bound state; reactivation requires the GEF eIF2B to catalyze GDP-to-GTP exchange,
      a cycle essential for continued rounds of initiation.
    supporting_text: |-
      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.
    reference_section_type: OTHER
  - statement: |
      Phosphorylation of eIF2alpha at the conserved Ser51 site by the kinase Gcn2 converts
      eIF2 from an eIF2B substrate into an inhibitor of eIF2B, lowering eIF2-GTP and ternary
      complex abundance and decreasing general translation initiation.
    supporting_text: |-
      A conserved translational-control mechanism in yeast is **phosphorylation of eIF2α at Ser51** by the kinase **Gcn2**. This single-site phosphorylation changes eIF2 from an eIF2B substrate into an **inhibitor of eIF2B**, lowering eIF2-GTP and TC abundance and thereby decreasing general translation initiation.
    reference_section_type: OTHER
  - statement: |
      In the general amino acid control (GAAC), amino acid limitation increases uncharged
      tRNAs that activate Gcn2 (via Gcn1/Gcn20), triggering Ser51 phosphorylation of
      eIF2alpha; this represses bulk initiation while derepressing GCN4 via uORF-mediated
      reinitiation control.
    supporting_text: |-
      In budding yeast, amino acid limitation increases **deacylated (uncharged) tRNAs**, which activate **Gcn2** (facilitated by **Gcn1/Gcn20**), causing **Ser51 phosphorylation of eIF2α**. This reduces TC abundance and globally represses initiation, while enabling selective translation of stress-response transcripts—classically **GCN4**, whose uORF architecture makes its translation inversely related to TC availability.
    reference_section_type: OTHER
  - statement: |
      eIF2alpha comprises three domains - an N-terminal OB-fold, a central alpha-helical
      domain, and a C-terminal alpha/beta domain that contacts eIF2gamma; the regulatory
      Ser51 lies in a mobile loop within the OB-fold domain.
    supporting_text: |-
      A yeast-focused synthesis of translation mechanisms describes eIF2α as composed of **three domains**: an **N-terminal OB-fold**, a **central α-helical domain**, and a **C-terminal α/β domain** that contacts eIF2γ. The **regulatory Ser51** is located in a mobile loop within the OB-fold domain.
    reference_section_type: OTHER
  - statement: |
      eIF2alpha contributes directly to start-codon selection fidelity: its unstructured
      N-terminal tail interacts with eIF1 to stabilize the open/scanning PIC and rearranges
      upon AUG recognition, and residue R53 contacts rRNA helix 23 while Arg55/Arg57 contact
      mRNA context near the start site.
    supporting_text: |-
      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
    reference_section_type: OTHER
  - statement: |
      The yeast Sui2 phosphosite Ser52 (UniProt numbering) corresponds to the conserved
      cross-species Ser51 regulatory residue used in most antibodies and studies.
    supporting_text: |-
      Sui2 phosphosite is adjacent to the canonical Ser51 numbering convention used in many studies/antibodies
    reference_section_type: OTHER
  - statement: |
      Phosphorylated eIF2 binds eIF2B with ~10-fold higher affinity than unphosphorylated
      eIF2 (Kd 3.5 nM vs 32.2 nM), supporting the model in which eIF2alpha-P sequesters and
      inhibits the eIF2B GEF.
    supporting_text: |-
      phosphorylated eIF2 was reported (in the paper’s cited measurement) to have ~10-fold higher affinity for eIF2B than unphosphorylated eIF2 (Kd **3.5 nM vs 32.2 nM**), supporting the sequestration/inhibition model.
    reference_section_type: OTHER
  - statement: |
      The Gcn2-eIF2alpha Ser51 switch operates in stress responses beyond classic amino
      acid starvation: a phospho-dead sui2-S51A mutant is acid-sensitive, and the pathway
      limits initiation under severe iron deficiency.
    supporting_text: |-
      a phosphorylation-defective **sui2-S51A** mutant is acid-sensitive, implicating the eIF2α phosphorylation switch in adaptation.
    reference_section_type: OTHER

SUI2

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

Comprehensive Research Report: Saccharomyces cerevisiae SUI2 (UniProt P20459; eIF2α)

1) Target verification and gene/protein identity (mandatory disambiguation)

2) Key concepts and definitions (current understanding)

2.1 eIF2 and the ternary complex (TC)

2.2 The eIF2 cycle and the role of eIF2B (GEF)

2.3 Central regulatory switch: Ser51 phosphorylation of Sui2/eIF2α

3) Molecular function of Sui2/eIF2α: precise mechanistic roles

3.1 Core function in initiation and start-codon selection

3.2 Structural/domain organization (linking UniProt domain expectations to literature)

4) Pathways and regulation involving SUI2/eIF2α in yeast

4.1 General amino acid control (GAAC) / ISR-like translational reprogramming

4.2 Cross-talk with TOR/Tap42 nutrient signaling

4.3 Snf1 (yeast AMPK) and phosphatase control of eIF2α-P levels

5) Cellular localization (where Sui2 functions)

6) Recent developments and latest research (prioritizing 2023–2024 where possible)

7) Current applications and real-world implementations (research and applied contexts)

8) Expert opinions and authoritative synthesis

9) Key statistics and quantitative data extracted from recent/representative studies

10) Summary functional annotation (narrative)

Evidence-synthesis table

Artifacts

Citations

📚 Additional Documentation

Curation Summary

SUI2 Gene Annotation Curation Review Summary

Gene Overview

Key Biological Role

Annotation Curation Results

Summary Statistics

High-Level Curation Strategy

Key Annotation Decisions

ACCEPTED ANNOTATIONS (23 total)

Molecular Function (5 annotations)

Biological Process (3 annotations)

Cellular Component (8 annotations)

MODIFIED ANNOTATIONS (1 total)

REMOVED ANNOTATIONS (2 total)

MARKED AS OVER-ANNOTATED (11 total)

KEPT AS NON-CORE (2 total)

Evidence Code Quality Assessment

Publications Used

Recommendations for Future Work

Core Annotations to Maintain

Missing Annotations Considered

Specific Interaction Annotations

Curation Standards Applied

Conclusion

📄 View Raw YAML