GCN2 (YDR283C, P15442) review notes

Literature search (2026-11-04)

No deep-research provider was available. Sources checked:

• SGD curated description (GCN2-deep-research-sgd.md, via just mod-description-deep-research yeast GCN2).
• UniProt P15442 curated free text (FUNCTION, SUBUNIT, PTM, DOMAIN, DISRUPTION PHENOTYPE).
• All 22 GOA-cited publications cached by just fetch-gene-pmids yeast GCN2 (all abstract-only in the cache).
• Attempted full text of PMID:21849502 (PMC3196070) via Europe PMC and the BioC OA service: not retrievable (HTTP 500 / not in OA subset).
• Reactome R-SCE-9633467, R-SCE-9633480, R-SCE-9633750.
• Context only: integrated stress response module, gcn2_variant annoton (module proposed in ai4curation/ai-gene-review#5904).

Findings

• GCN2 is the only eIF2alpha kinase of budding yeast; it phosphorylates eIF2alpha (Sui2) Ser51 (UniProt Ser-52) in starved cells, which mediates GCN4 translational derepression [PMID:1739968 "In vitro, GCN2 specifically phosphorylates the alpha subunit of rabbit or yeast eIF-2"; "Substitution of Ser-51 with alanine eliminates phosphorylation of eIF-2 alpha by GCN2 in vivo and in vitro and abolishes increased expression of GCN4"].
• Activation by uncharged tRNA via the HisRS-like domain plus C-terminal domain [PMID:10983975 "GCN2 bound several deacylated tRNAs with similar affinities, and aminoacylation of tRNAphe weakened its interaction with GCN2"; PMID:7623840 "uncharged tRNA can bind to the synthetase-related domain of GCN2"].
• Requires GCN1/GCN20 [PMID:7621831 "GCN1 and GCN20 are components of a protein complex that couples the kinase activity of GCN2 to the availability of amino acids"; PMID:11101534].
• Ribosome association, loose (salt-sensitive), via C-terminus PMID:2038314; C-terminal DRBD-like segment binds dsRNA in vitro PMID:9430731.
• Dimerization PMID:9566889; autophosphorylation PMID:2188100; conserved salt bridge for activation PMID:17202131.
• Responds to purine limitation too PMID:8336737.
• Phosphorylates Kog1 to down-regulate TORC1 PMID:28057755.
• G1/S DNA-damage checkpoint role (abstract-less cache) [PMID:17890903 title].
• eEF1A binds Gcn2 CTD and inhibits it PMID:21849502. GOA row GO:0031369 translation initiation factor binding WITH P38912 (TIF11/eIF1A) from this paper; the abstract only names eEF1A (an elongation factor). UniProt SUBUNIT text also says "TIF11" for this interaction. Possible eEF1A/eIF1A conflation; full text not available, left UNDECIDED.

Decisions summary

Core: GO:0004694 eIF2alpha kinase activity; GO:0140469 GCN2-mediated signaling; tRNA binding (sensor); ribosome binding; cytosol.