{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P33892","secondaryAccessions":["D6VTV8"],"uniProtkbId":"GCN1_YEAST","entryAudit":{"firstPublicDate":"1994-02-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1994-02-01","entryVersion":206,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Saccharomyces cerevisiae (strain ATCC 204508 / S288c)","commonName":"Baker's yeast","taxonId":559292,"lineage":["Eukaryota","Fungi","Dikarya","Ascomycota","Saccharomycotina","Saccharomycetes","Saccharomycetales","Saccharomycetaceae","Saccharomyces"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"eIF-2-alpha kinase activator GCN1"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"SGD","id":"S000003163"}],"value":"General control non-derepressible protein 1"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Translational activator GCN1"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"8497269"},{"evidenceCode":"ECO:0000312","source":"SGD","id":"S000003163"}],"value":"GCN1"},"orderedLocusNames":[{"value":"YGL195W"}],"orfNames":[{"value":"G1318"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q92616"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10733573"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10801780"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11350982"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15722345"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24333428"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33338396"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33790014"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36441697"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7621831"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8497269"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9234705"}],"value":"Ribosome collision sensor that activates a translation quality control pathway when a ribosome has stalled during translation (PubMed:33790014). Directly binds to the ribosome and acts as a sentinel for colliding ribosomes (By similarity). GCN1 also acts as a positive activator of the integrated stress response (ISR) by mediating activation of GCN2 in response to low amino acid, carbon, or purine availability (PubMed:10733573, PubMed:24333428, PubMed:33338396, PubMed:8497269). Component of the GCN1-GCN20 complex that forms a complex with GCN2 on translating ribosomes: during this process, GCN1 acts as a chaperone to facilitate delivery of uncharged tRNAs that enter the A-site of ribosomes to the tRNA-binding domain of GCN2, and hence stimulating GCN2 kinase activity, leading to phosphorylation of eukaryotic translation initiation factor 2 (eIF-2-alpha/SUI2) (PubMed:15722345, PubMed:36441697, PubMed:7621831, PubMed:9234705). eIF-2-alpha/SUI2 phosphorylation converts eIF-2-alpha/SUI2 into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator GCN4, and hence allowing GCN4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:10801780, PubMed:11350982, PubMed:15722345, PubMed:8497269)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10775272"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10801780"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11101534"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11350982"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15126500"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15722345"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19448108"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21239490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21849502"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22404850"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22888004"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25437641"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36441697"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7621831"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9234705"}],"value":"Interacts (via N- and C-terminus) with GCN2 (via N-terminal RWD domain); this interaction stimulates GCN2 kinase activity in a GCN20-dependent manner in response to amino acid starvation (PubMed:10775272, PubMed:10801780, PubMed:11101534, PubMed:11350982, PubMed:15126500, PubMed:15722345, PubMed:21849502, PubMed:36441697). Interacts (via C-terminus) with GCN20 (via N-terminus); this interaction stimulates GCN2 kinase activity in response to amino acid starvation (PubMed:11101534, PubMed:7621831, PubMed:9234705). The GCN1-GCN20 complex interacts with GCN2 on translating ribosomes in amino acid-starved cells; GCN1 may bind near the ribosomal A-site and promotes the transfer of uncharged tRNAs from the A-site to the tRNA-binding domain in GCN2 for its subsequent kinase activation, and hence allowing GCN4 translational activation and derepression of amino acid biosynthetic genes (PubMed:10775272, PubMed:11101534, PubMed:7621831, PubMed:9234705). Interacts (via C-terminus) with YIH1 (via N-terminus); this interaction reduces the GCN1-GCN20 complex formation and prevents the interaction of GCN1 with GCN2 and GCN2 kinase activation in amino acid-starved cells (PubMed:15126500, PubMed:21239490, PubMed:22404850). Interacts with GIR2; this interaction prevents the interaction of GCN1 with GCN2 and GCN2 kinase activation in amino acid-starved cells (PubMed:19448108). Interacts (via middle region) with RPS10A and RPS10B; these interactions are direct and promote GCN2 kinase activation (PubMed:25437641). Associates (via N-terminus) with ribosomes; this association is stimulated in a ATP- and GCN20-dependent manner and is necessary to activate GCN2 kinase activity (PubMed:11101534, PubMed:15722345, PubMed:19448108, PubMed:21849502, PubMed:22888004, PubMed:25437641, PubMed:7621831, PubMed:9234705)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P33892","intActId":"EBI-7442"},"interactantTwo":{"uniProtKBAccession":"P43535","geneName":"GCN20","intActId":"EBI-7423"},"numberOfExperiments":4,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9234705"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9234705"}],"value":"The EF3-like region is necessary and sufficient for interaction with GCN20 (PubMed:9234705)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36441697"}],"value":"The RWDBD (RWD-binding domain) region mediates binding to RWD domain-containing proteins, such as GCN2"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10733573"}],"value":"Inhibits GCN4 derepression in glucose, amino acid, or purine-starved cells"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14562106"}],"value":"Present with 7330 molecules/cell in log phase SD medium"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the GCN1 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":2672,"modifier":"EXACT"}},"description":"eIF-2-alpha kinase activator 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