ID GCN1_YEAST Reviewed; 2672 AA. AC P33892; D6VTV8; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 02-SEP-2026, entry version 206. DE RecName: Full=eIF-2-alpha kinase activator GCN1 {ECO:0000305}; DE AltName: Full=General control non-derepressible protein 1 {ECO:0000312|SGD:S000003163}; DE AltName: Full=Translational activator GCN1 {ECO:0000305}; GN Name=GCN1 {ECO:0000303|PubMed:8497269, ECO:0000312|SGD:S000003163}; GN OrderedLocusNames=YGL195W; ORFNames=G1318; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION. RX PubMed=8497269; DOI=10.1128/mcb.13.6.3541-3556.1993; RA Marton M.J., Crouch D., Hinnebusch A.G.; RT "GCN1, a translational activator of GCN4 in Saccharomyces cerevisiae, is RT required for phosphorylation of eukaryotic translation initiation factor 2 RT by protein kinase GCN2."; RL Mol. Cell. Biol. 13:3541-3556(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 96604 / S288c / FY1679; RX PubMed=9046087; RX DOI=10.1002/(sici)1097-0061(199701)13:1<55::aid-yea48>3.0.co;2-9; RA Coglievina M., Klima R., Bertani I., Delneri D., Zaccaria P., Bruschi C.V.; RT "Sequencing of a 40.5 kb fragment located on the left arm of chromosome VII RT from Saccharomyces cerevisiae."; RL Yeast 13:55-64(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169869; DOI=10.1038/387s081; RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H., RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII."; RL Nature 387:81-84(1997). RN [4] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [5] RP FUNCTION, INTERACTION WITH GCN20, AND ASSOCIATION WITH RIBOSOMES. RX PubMed=7621831; DOI=10.1002/j.1460-2075.1995.tb07321.x; RA Vazquez de Aldana C.R., Marton M.J., Hinnebusch A.G.; RT "GCN20, a novel ATP binding cassette protein, and GCN1 reside in a complex RT that mediates activation of the eIF-2 alpha kinase GCN2 in amino acid- RT starved cells."; RL EMBO J. 14:3184-3199(1995). RN [6] RP FUNCTION, INTERACTION WITH GCN20, ASSOCIATION WITH RIBOSOMES, SUBCELLULAR RP LOCATION, DOMAIN, AND MUTAGENESIS OF GLY-1444. RX PubMed=9234705; DOI=10.1128/mcb.17.8.4474; RA Marton M.J., Vazquez de Aldana C.R., Qiu H., Chakraburtty K., RA Hinnebusch A.G.; RT "Evidence that GCN1 and GCN20, translational regulators of GCN4, function RT on elongating ribosomes in activation of eIF2alpha kinase GCN2."; RL Mol. Cell. Biol. 17:4474-4489(1997). RN [7] RP INTERACTION WITH GCN2, AND IDENTIFICATION IN A COMPLEX WITH GCN2 AND GCN20. RX PubMed=10775272; DOI=10.1093/emboj/19.8.1887; RA Garcia-Barrio M., Dong J., Ufano S., Hinnebusch A.G.; RT "Association of GCN1-GCN20 regulatory complex with the N-terminus of RT eIF2alpha kinase GCN2 is required for GCN2 activation."; RL EMBO J. 19:1887-1899(2000). RN [8] RP INTERACTION WITH GCN2 AND GCN20, IDENTIFICATION IN A COMPLEX WITH GCN2 AND RP GCN20, ASSOCIATION WITH RIBOSOMES, AND MUTAGENESIS OF ARG-2259. RX PubMed=11101534; DOI=10.1093/emboj/19.23.6622; RA Sattlegger E., Hinnebusch A.G.; RT "Separate domains in GCN1 for binding protein kinase GCN2 and ribosomes are RT required for GCN2 activation in amino acid-starved cells."; RL EMBO J. 19:6622-6633(2000). RN [9] RP FUNCTION, AND INTERACTION WITH GCN2. RX PubMed=10801780; DOI=10.1074/jbc.c000262200; RA Kubota H., Sakaki Y., Ito T.; RT "GI domain-mediated association of the eukaryotic initiation factor 2alpha RT kinase GCN2 with its activator GCN1 is required for general amino acid RT control in budding yeast."; RL J. Biol. Chem. 275:20243-20246(2000). RN [10] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=10733573; DOI=10.1128/mcb.20.8.2706-2717.2000; RA Yang R., Wek S.A., Wek R.C.; RT "Glucose limitation induces GCN4 translation by activation of Gcn2 protein RT kinase."; RL Mol. Cell. Biol. 20:2706-2717(2000). RN [11] RP FUNCTION, INTERACTION WITH GCN2, AND MUTAGENESIS OF PHE-2291; SER-2304 AND RP LEU-2353. RX PubMed=11350982; DOI=10.1074/jbc.m011793200; RA Kubota H., Ota K., Sakaki Y., Ito T.; RT "Budding yeast GCN1 binds the GI domain to activate the eIF2alpha kinase RT GCN2."; RL J. Biol. Chem. 276:17591-17596(2001). RN [12] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [13] RP INTERACTION WITH YIH1, AND MUTAGENESIS OF ARG-2259. RX PubMed=15126500; DOI=10.1074/jbc.m404009200; RA Sattlegger E., Swanson M.J., Ashcraft E.A., Jennings J.L., Fekete R.A., RA Link A.J., Hinnebusch A.G.; RT "YIH1 is an actin-binding protein that inhibits protein kinase GCN2 and RT impairs general amino acid control when overexpressed."; RL J. Biol. Chem. 279:29952-29962(2004). RN [14] RP FUNCTION, INTERACTION WITH GCN20, ASSOCIATION WITH RIBOSOMES, AND RP MUTAGENESIS OF 757-LYS-LYS-758; LYS-762; LYS-765; LYS-775; 777-ARG-LYS-778; RP 782-LYS-LYS-783; 786-LYS-LYS-787; LYS-790; GLU-1458 AND 1461-TRP--ARG-1465. RX PubMed=15722345; DOI=10.1074/jbc.m414566200; RA Sattlegger E., Hinnebusch A.G.; RT "Polyribosome binding by GCN1 is required for full activation of eukaryotic RT translation initiation factor 2{alpha} kinase GCN2 during amino acid RT starvation."; RL J. Biol. Chem. 280:16514-16521(2005). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC STRAIN=ADR376; RX PubMed=17330950; DOI=10.1021/pr060559j; RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., RA Elias J.E., Gygi S.P.; RT "Large-scale phosphorylation analysis of alpha-factor-arrested RT Saccharomyces cerevisiae."; RL J. Proteome Res. 6:1190-1197(2007). RN [16] RP INTERACTION WITH GIR2, AND ASSOCIATION WITH RIBOSOMES. RX PubMed=19448108; DOI=10.1128/ec.00356-08; RA Wout P.K., Sattlegger E., Sullivan S.M., Maddock J.R.; RT "Saccharomyces cerevisiae Rbg1 protein and its binding partner Gir2 RT interact on polyribosomes with Gcn1."; RL Eukaryot. Cell 8:1061-1071(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights RT into evolution."; RL Science 325:1682-1686(2009). RN [18] RP INTERACTION WITH YIH1, AND MUTAGENESIS OF ARG-2259. RX PubMed=21239490; DOI=10.1074/jbc.m110.171587; RA Sattlegger E., Barbosa J.A., Moraes M.C., Martins R.M., Hinnebusch A.G., RA Castilho B.A.; RT "Gcn1 and actin binding to Yih1: implications for activation of the eIF2 RT kinase GCN2."; RL J. Biol. Chem. 286:10341-10355(2011). RN [19] RP INTERACTION WITH YIH1. RX PubMed=22404850; DOI=10.1111/j.1742-4658.2012.08553.x; RA Waller T., Lee S.J., Sattlegger E.; RT "Evidence that Yih1 resides in a complex with ribosomes."; RL FEBS J. 279:1761-1776(2012). RN [20] RP FUNCTION. RX PubMed=24333428; DOI=10.1016/j.bbrc.2013.12.021; RA Cambiaghi T.D., Pereira C.M., Shanmugam R., Bolech M., Wek R.C., RA Sattlegger E., Castilho B.A.; RT "Evolutionarily conserved IMPACT impairs various stress responses that RT require GCN1 for activating the eIF2 kinase GCN2."; RL Biochem. Biophys. Res. Commun. 443:592-597(2014). RN [21] RP INTERACTION WITH GCN2, AND ASSOCIATION WITH RIBOSOMES. RX PubMed=21849502; DOI=10.1074/jbc.m111.248898; RA Visweswaraiah J., Lageix S., Castilho B.A., Izotova L., Kinzy T.G., RA Hinnebusch A.G., Sattlegger E.; RT "Evidence that eukaryotic translation elongation factor 1A (eEF1A) binds RT the Gcn2 protein C terminus and inhibits Gcn2 activity."; RL J. Biol. Chem. 286:36568-36579(2011). RN [22] RP ASSOCIATION WITH RIBOSOMES, AND MUTAGENESIS OF 757-LYS-LYS-758; LYS-762; RP LYS-765; LYS-775; 777-ARG-LYS-778; 782-LYS-LYS-783; 786-LYS-LYS-787 AND RP LYS-790. RX PubMed=22888004; DOI=10.1074/jbc.m112.368266; RA Visweswaraiah J., Lee S.J., Hinnebusch A.G., Sattlegger E.; RT "Overexpression of eukaryotic translation elongation factor 3 impairs Gcn2 RT protein activation."; RL J. Biol. Chem. 287:37757-37768(2012). RN [23] RP INTERACTION WITH RPS10A AND RPS10B, AND ASSOCIATION WITH RIBOSOMES. RX PubMed=25437641; DOI=10.1042/bj20140782; RA Lee S.J., Swanson M.J., Sattlegger E.; RT "Gcn1 contacts the small ribosomal protein Rps10, which is required for RT full activation of the protein kinase Gcn2."; RL Biochem. J. 466:547-559(2015). RN [24] RP RWDBD DOMAIN. RX PubMed=28526057; DOI=10.1186/s13062-017-0184-3; RA Rakesh R., Krishnan R., Sattlegger E., Srinivasan N.; RT "Recognition of a structural domain (RWDBD) in Gcn1 proteins that interacts RT with the RWD domain containing proteins."; RL Biol. Direct 12:12-12(2017). RN [25] RP FUNCTION. RX PubMed=33338396; DOI=10.1016/j.molcel.2020.11.033; RA Yan L.L., Zaher H.S.; RT "Ribosome quality control antagonizes the activation of the integrated RT stress response on colliding ribosomes."; RL Mol. Cell 81:614-628(2021). RN [26] RP FUNCTION, RWDBD DOMAIN, INTERACTION WITH GCN2, AND MUTAGENESIS OF ASN-2224; RP ARG-2227; ASN-2245; LYS-2247; SER-2251; ARG-2259; VAL-2261; GLU-2263; RP ARG-2264; LYS-2270; ARG-2289; PHE-2291; GLN-2294; ARG-2297; LYS-2301; RP ASP-2305; GLU-2309; ASP-2330; GLU-2335 AND GLU-2382. RX PubMed=36441697; DOI=10.1371/journal.pone.0277648; RA Gottfried S., Koloamatangi S.M.B.M.J., Daube C., Schiemann A.H., RA Sattlegger E.; RT "A genetic approach to identify amino acids in Gcn1 required for Gcn2 RT activation."; RL PLoS ONE 17:e0277648-e0277648(2022). RN [27] {ECO:0007744|PDB:7NRC} RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) OF 1324-1638 IN COMPLEX RP WITH STALLED RIBOSOME, AND FUNCTION. RX PubMed=33790014; DOI=10.1073/pnas.2022756118; RA Pochopien A.A., Beckert B., Kasvandik S., Berninghausen O., Beckmann R., RA Tenson T., Wilson D.N.; RT "Structure of Gcn1 bound to stalled and colliding 80S ribosomes."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). CC -!- FUNCTION: Ribosome collision sensor that activates a translation CC quality control pathway when a ribosome has stalled during translation CC (PubMed:33790014). Directly binds to the ribosome and acts as a CC sentinel for colliding ribosomes (By similarity). GCN1 also acts as a CC positive activator of the integrated stress response (ISR) by mediating CC activation of GCN2 in response to low amino acid, carbon, or purine CC availability (PubMed:10733573, PubMed:24333428, PubMed:33338396, CC PubMed:8497269). Component of the GCN1-GCN20 complex that forms a CC complex with GCN2 on translating ribosomes: during this process, GCN1 CC acts as a chaperone to facilitate delivery of uncharged tRNAs that CC enter the A-site of ribosomes to the tRNA-binding domain of GCN2, and CC hence stimulating GCN2 kinase activity, leading to phosphorylation of CC eukaryotic translation initiation factor 2 (eIF-2-alpha/SUI2) CC (PubMed:15722345, PubMed:36441697, PubMed:7621831, PubMed:9234705). CC eIF-2-alpha/SUI2 phosphorylation converts eIF-2-alpha/SUI2 into a CC global protein synthesis inhibitor, leading to a global attenuation of CC cap-dependent translation, and thus to a reduced overall utilization of CC amino acids, while concomitantly initiating the preferential CC translation of ISR-specific mRNAs, such as the transcriptional CC activator GCN4, and hence allowing GCN4-mediated reprogramming of amino CC acid biosynthetic gene expression to alleviate nutrient depletion CC (PubMed:10801780, PubMed:11350982, PubMed:15722345, PubMed:8497269). CC {ECO:0000250|UniProtKB:Q92616, ECO:0000269|PubMed:10733573, CC ECO:0000269|PubMed:10801780, ECO:0000269|PubMed:11350982, CC ECO:0000269|PubMed:15722345, ECO:0000269|PubMed:24333428, CC ECO:0000269|PubMed:33338396, ECO:0000269|PubMed:33790014, CC ECO:0000269|PubMed:36441697, ECO:0000269|PubMed:7621831, CC ECO:0000269|PubMed:8497269, ECO:0000269|PubMed:9234705}. CC -!- SUBUNIT: Interacts (via N- and C-terminus) with GCN2 (via N-terminal CC RWD domain); this interaction stimulates GCN2 kinase activity in a CC GCN20-dependent manner in response to amino acid starvation CC (PubMed:10775272, PubMed:10801780, PubMed:11101534, PubMed:11350982, CC PubMed:15126500, PubMed:15722345, PubMed:21849502, PubMed:36441697). CC Interacts (via C-terminus) with GCN20 (via N-terminus); this CC interaction stimulates GCN2 kinase activity in response to amino acid CC starvation (PubMed:11101534, PubMed:7621831, PubMed:9234705). The GCN1- CC GCN20 complex interacts with GCN2 on translating ribosomes in amino CC acid-starved cells; GCN1 may bind near the ribosomal A-site and CC promotes the transfer of uncharged tRNAs from the A-site to the tRNA- CC binding domain in GCN2 for its subsequent kinase activation, and hence CC allowing GCN4 translational activation and derepression of amino acid CC biosynthetic genes (PubMed:10775272, PubMed:11101534, PubMed:7621831, CC PubMed:9234705). Interacts (via C-terminus) with YIH1 (via N-terminus); CC this interaction reduces the GCN1-GCN20 complex formation and prevents CC the interaction of GCN1 with GCN2 and GCN2 kinase activation in amino CC acid-starved cells (PubMed:15126500, PubMed:21239490, PubMed:22404850). CC Interacts with GIR2; this interaction prevents the interaction of GCN1 CC with GCN2 and GCN2 kinase activation in amino acid-starved cells CC (PubMed:19448108). Interacts (via middle region) with RPS10A and CC RPS10B; these interactions are direct and promote GCN2 kinase CC activation (PubMed:25437641). Associates (via N-terminus) with CC ribosomes; this association is stimulated in a ATP- and GCN20-dependent CC manner and is necessary to activate GCN2 kinase activity CC (PubMed:11101534, PubMed:15722345, PubMed:19448108, PubMed:21849502, CC PubMed:22888004, PubMed:25437641, PubMed:7621831, PubMed:9234705). CC {ECO:0000269|PubMed:10775272, ECO:0000269|PubMed:10801780, CC ECO:0000269|PubMed:11101534, ECO:0000269|PubMed:11350982, CC ECO:0000269|PubMed:15126500, ECO:0000269|PubMed:15722345, CC ECO:0000269|PubMed:19448108, ECO:0000269|PubMed:21239490, CC ECO:0000269|PubMed:21849502, ECO:0000269|PubMed:22404850, CC ECO:0000269|PubMed:22888004, ECO:0000269|PubMed:25437641, CC ECO:0000269|PubMed:36441697, ECO:0000269|PubMed:7621831, CC ECO:0000269|PubMed:9234705}. CC -!- INTERACTION: CC P33892; P43535: GCN20; NbExp=4; IntAct=EBI-7442, EBI-7423; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9234705}. CC -!- DOMAIN: The EF3-like region is necessary and sufficient for interaction CC with GCN20 (PubMed:9234705). {ECO:0000269|PubMed:9234705}. CC -!- DOMAIN: The RWDBD (RWD-binding domain) region mediates binding to RWD CC domain-containing proteins, such as GCN2. CC {ECO:0000269|PubMed:36441697}. CC -!- DISRUPTION PHENOTYPE: Inhibits GCN4 derepression in glucose, amino CC acid, or purine-starved cells. {ECO:0000269|PubMed:10733573}. CC -!- MISCELLANEOUS: Present with 7330 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the GCN1 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L12467; AAA34635.1; -; Genomic_DNA. DR EMBL; X91837; CAA62949.1; -; Genomic_DNA. DR EMBL; Z72717; CAA96907.1; -; Genomic_DNA. DR EMBL; BK006941; DAA07919.1; -; Genomic_DNA. DR PIR; A48126; A48126. DR RefSeq; NP_011320.3; NM_001181060.3. DR PDB; 7NRC; EM; 3.90 A; A=1324-1638. DR AlphaFoldDB; P33892; -. DR EMDB; EMD-12534; -. DR BioGRID; 33062; 507. DR ComplexPortal; CPX-1808; GCN1-GCN20 complex. DR DIP; DIP-2344N; -. DR FunCoup; P33892; 1743. DR IntAct; P33892; 145. DR MINT; P33892; -. DR STRING; 4932.YGL195W; -. DR iPTMnet; P33892; -. DR PaxDb; 4932-YGL195W; -. DR PeptideAtlas; P33892; -. DR EnsemblFungi; YGL195W_mRNA; YGL195W; YGL195W. DR GeneID; 852680; -. DR KEGG; sce:YGL195W; -. DR AGR; SGD:S000003163; -. DR SGD; S000003163; GCN1. DR VEuPathDB; FungiDB:YGL195W; -. DR eggNOG; KOG1242; Eukaryota. DR HOGENOM; CLU_000504_2_0_1; -. DR InParanoid; P33892; -. DR OMA; SMKIFLH; -. DR OrthoDB; 5148094at2759; -. DR BioCyc; YEAST:G3O-30676-MONOMER; -. DR BioGRID-ORCS; 852680; 0 hits in 10 CRISPR screens. DR CD-CODE; E03F929F; Stress granule. DR PRO; PR:P33892; -. DR Proteomes; UP000002311; Chromosome VII. DR RNAct; P33892; protein. DR GO; GO:0005737; C:cytoplasm; EXP:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:SGD. DR GO; GO:0022626; C:cytosolic ribosome; IDA:SGD. DR GO; GO:0005739; C:mitochondrion; HDA:SGD. DR GO; GO:0043008; F:ATP-dependent protein binding; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0019887; F:protein kinase regulator activity; IMP:SGD. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:UniProtKB. DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB. DR GO; GO:0170011; F:stalled ribosome sensor activity; IDA:UniProt. DR GO; GO:0031369; F:translation initiation factor binding; IPI:UniProtKB. DR GO; GO:0034198; P:cellular response to amino acid starvation; IDA:UniProtKB. DR GO; GO:0140469; P:GCN2-mediated signaling; IDA:UniProtKB. DR GO; GO:0033674; P:positive regulation of kinase activity; IMP:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0071264; P:positive regulation of translational initiation in response to starvation; IDA:UniProtKB. DR GO; GO:1990611; P:regulation of cytoplasmic translational initiation in response to stress; IMP:UniProtKB. DR GO; GO:0006417; P:regulation of translation; IBA:GO_Central. DR GO; GO:0006448; P:regulation of translational elongation; IMP:SGD. DR GO; GO:0072344; P:rescue of stalled cytosolic ribosome; IDA:UniProtKB. DR FunFam; 1.25.10.10:FF:000090; eIF-2-alpha kinase activator GCN1; 1. DR FunFam; 1.25.10.10:FF:001254; eIF-2-alpha kinase activator GCN1; 1. DR FunFam; 1.25.10.10:FF:001479; eIF-2-alpha kinase activator GCN1; 1. DR FunFam; 1.25.10.10:FF:000096; eIF-2-alpha kinase activator gcn1; 1. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 6. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR022716; Gcn1_N. DR InterPro; IPR056810; GNC1-like_N. DR InterPro; IPR057546; HEAT_GCN1. DR InterPro; IPR060078; HEAT_GCN1_2. DR InterPro; IPR063431; HEAT_GCN1_C_2. DR InterPro; IPR056809; HEAT_GCN1_fung. DR InterPro; IPR021133; HEAT_type_2. DR InterPro; IPR034085; TOG. DR PANTHER; PTHR23346:SF7; STALLED RIBOSOME SENSOR GCN1; 1. DR PANTHER; PTHR23346; TRANSLATIONAL ACTIVATOR GCN1-RELATED; 1. DR Pfam; PF12074; Gcn1_N; 2. DR Pfam; PF24993; GNC1_N; 1. DR Pfam; PF24984; HEAT_EF3_GNC1; 1. DR Pfam; PF24987; HEAT_EF3_N; 1. DR Pfam; PF23271; HEAT_GCN1; 1. DR Pfam; PF26715; HEAT_GCN1_2; 1. DR Pfam; PF25801; HEAT_GCN1_C_2; 1. DR Pfam; PF24916; HEAT_GCN1_fung; 1. DR SMART; SM01349; TOG; 1. DR SUPFAM; SSF48371; ARM repeat; 4. DR PROSITE; PS50077; HEAT_REPEAT; 4. DR PDBsum; 7NRC; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Cytoplasm; Reference proteome; Repeat; KW Stress response; Translation regulation. FT CHAIN 1..2672 FT /note="eIF-2-alpha kinase activator GCN1" FT /id="PRO_0000087444" FT REPEAT 5..42 FT /note="HEAT 1" FT /evidence="ECO:0000255" FT REPEAT 79..117 FT /note="HEAT 2" FT /evidence="ECO:0000255" FT REPEAT 174..211 FT /note="HEAT 3" FT /evidence="ECO:0000255" FT REPEAT 227..267 FT /note="HEAT 4" FT /evidence="ECO:0000255" FT REPEAT 329..366 FT /note="HEAT 5" FT /evidence="ECO:0000255" FT REPEAT 372..410 FT /note="HEAT 6" FT /evidence="ECO:0000255" FT REPEAT 509..549 FT /note="HEAT 7" FT /evidence="ECO:0000255" FT REPEAT 611..648 FT /note="HEAT 8" FT /evidence="ECO:0000255" FT REPEAT 706..745 FT /note="HEAT 9" FT /evidence="ECO:0000255" FT REPEAT 902..932 FT /note="HEAT 10" FT /evidence="ECO:0000255" FT REPEAT 933..970 FT /note="HEAT 11" FT /evidence="ECO:0000255" FT REPEAT 975..994 FT /note="HEAT 12; degenerate" FT /evidence="ECO:0000255" FT REPEAT 995..1030 FT /note="HEAT 13; degenerate" FT /evidence="ECO:0000255" FT REPEAT 1031..1067 FT /note="HEAT 14" FT /evidence="ECO:0000255" FT REPEAT 1099..1138 FT /note="HEAT 15" FT /evidence="ECO:0000255" FT REPEAT 1185..1224 FT /note="HEAT 16" FT /evidence="ECO:0000255" FT REPEAT 1243..1281 FT /note="HEAT 17" FT /evidence="ECO:0000255" FT REPEAT 1284..1321 FT /note="HEAT 18" FT /evidence="ECO:0000255" FT REPEAT 1363..1401 FT /note="HEAT 19" FT /evidence="ECO:0000255" FT REPEAT 1405..1442 FT /note="HEAT 20" FT /evidence="ECO:0000255" FT REPEAT 1444..1480 FT /note="HEAT 21" FT /evidence="ECO:0000255" FT REPEAT 1484..1521 FT /note="HEAT 22" FT /evidence="ECO:0000255" FT REPEAT 1523..1559 FT /note="HEAT 23" FT /evidence="ECO:0000255" FT REPEAT 1561..1598 FT /note="HEAT 24" FT /evidence="ECO:0000255" FT REPEAT 1603..1640 FT /note="HEAT 25" FT /evidence="ECO:0000255" FT REPEAT 1641..1679 FT /note="HEAT 26" FT /evidence="ECO:0000255" FT REPEAT 1681..1717 FT /note="HEAT 27" FT /evidence="ECO:0000255" FT REPEAT 1721..1758 FT /note="HEAT 28" FT /evidence="ECO:0000255" FT REPEAT 1760..1796 FT /note="HEAT 29" FT /evidence="ECO:0000255" FT REPEAT 1825..1862 FT /note="HEAT 30" FT /evidence="ECO:0000255" FT REPEAT 1863..1903 FT /note="HEAT 31" FT /evidence="ECO:0000255" FT REPEAT 1905..1942 FT /note="HEAT 32" FT /evidence="ECO:0000255" FT REPEAT 1947..1984 FT /note="HEAT 33" FT /evidence="ECO:0000255" FT REPEAT 1985..2024 FT /note="HEAT 34" FT /evidence="ECO:0000255" FT REPEAT 2026..2055 FT /note="HEAT 35" FT /evidence="ECO:0000255" FT REPEAT 2057..2095 FT /note="HEAT 36" FT /evidence="ECO:0000255" FT REPEAT 2097..2134 FT /note="HEAT 37" FT /evidence="ECO:0000255" FT REPEAT 2138..2175 FT /note="HEAT 38" FT /evidence="ECO:0000255" FT REPEAT 2206..2243 FT /note="HEAT 39" FT /evidence="ECO:0000255" FT REPEAT 2250..2286 FT /note="HEAT 40" FT /evidence="ECO:0000255" FT REPEAT 2290..2328 FT /note="HEAT 41" FT /evidence="ECO:0000255" FT REPEAT 2347..2384 FT /note="HEAT 42" FT /evidence="ECO:0000255" FT REPEAT 2392..2429 FT /note="HEAT 43" FT /evidence="ECO:0000255" FT REPEAT 2450..2487 FT /note="HEAT 44" FT /evidence="ECO:0000255" FT REPEAT 2506..2546 FT /note="HEAT 45" FT /evidence="ECO:0000255" FT REGION 1330..1641 FT /note="EF3-like region" FT /evidence="ECO:0000303|PubMed:9234705" FT REGION 2207..2356 FT /note="RWDBD region" FT /evidence="ECO:0000305|PubMed:28526057" FT MUTAGEN 757..758 FT /note="KK->AA,DD: Does not inhibit interaction with GCN20, FT reduces ribosome binding, ribosome binding by GCN20, weakly FT impairs eIF-2-alpha phosphorylation but strongly impairs FT eIF-2-alpha phosphorylation in a YEF3-dependent manner; FT when associated with A-762; A-765; A-775; 777-A-A-778; FT 782-A-A-783; 786-A-A-787 and A-790." FT /evidence="ECO:0000269|PubMed:15722345, FT ECO:0000269|PubMed:22888004" FT MUTAGEN 762 FT /note="K->A: Does not inhibit interaction with GCN20, FT reduces ribosome binding, ribosome binding by GCN20, weakly FT impairs eIF-2-alpha phosphorylation but strongly impairs FT eIF-2-alpha phosphorylation in a YEF3-dependent manner; FT when associated with A-757-758-A; A-765; A-775; FT 777-A-A-778; 782-A-A-783; 786-A-A-787 and A-790." FT /evidence="ECO:0000269|PubMed:15722345, FT ECO:0000269|PubMed:22888004" FT MUTAGEN 765 FT /note="K->A: Does not inhibit interaction with GCN20, FT reduces ribosome binding, ribosome binding by GCN20, weakly FT impairs eIF-2-alpha phosphorylation but strongly impairs FT eIF-2-alpha phosphorylation in a YEF3-dependent manner; FT when associated with A-757-758-A; A-762; A-775; FT 777-A-A-778; 782-A-A-783; 786-A-A-787 and A-790." FT /evidence="ECO:0000269|PubMed:15722345, FT ECO:0000269|PubMed:22888004" FT MUTAGEN 775 FT /note="K->A: Does not inhibit interaction with GCN20, FT reduces ribosome binding, ribosome binding by GCN20, weakly FT impairs eIF-2-alpha phosphorylation but strongly impairs FT eIF-2-alpha phosphorylation in a YEF3-dependent manner; FT when associated with A-757-758-A; A-762; A-765; FT 777-A-A-778; 782-A-A-783; 786-A-A-787 and A-790." FT /evidence="ECO:0000269|PubMed:15722345, FT ECO:0000269|PubMed:22888004" FT MUTAGEN 777..778 FT /note="RK->AA: Does not inhibit interaction with GCN20, FT reduces ribosome binding, ribosome binding by GCN20, weakly FT impairs eIF-2-alpha phosphorylation but strongly impairs FT eIF-2-alpha phosphorylation in a YEF3-dependent manner; FT when associated with A-757-758-A; A-762; A-765; A-775; FT 782-A-A-783; 786-A-A-787 and A-790." FT /evidence="ECO:0000269|PubMed:15722345, FT ECO:0000269|PubMed:22888004" FT MUTAGEN 782..783 FT /note="KK->AA: Does not inhibit interaction with GCN20, FT reduces ribosome binding, ribosome binding by GCN20, weakly FT impairs eIF-2-alpha phosphorylation but strongly impairs FT eIF-2-alpha phosphorylation in a YEF3-dependent manner; FT when associated with A-757-758-A; A-762; A-765; A-775; FT 777-A-A-778; 786-A-A-787 and A-790." FT /evidence="ECO:0000269|PubMed:15722345, FT ECO:0000269|PubMed:22888004" FT MUTAGEN 786..787 FT /note="KK->AA: Does not inhibit interaction with GCN20, FT reduces ribosome binding, ribosome binding by GCN20, weakly FT impairs eIF-2-alpha phosphorylation but strongly impairs FT eIF-2-alpha phosphorylation in a YEF3-dependent manner; FT when associated with A-757-758-A; A-762; A-765; A-775; FT 777-A-A-778; 782-A-A-783 and A-790." FT /evidence="ECO:0000269|PubMed:15722345, FT ECO:0000269|PubMed:22888004" FT MUTAGEN 790 FT /note="K->A: Does not inhibit interaction with GCN20, FT reduces ribosome binding, ribosome binding by GCN20, weakly FT impairs eIF-2-alpha phosphorylation but strongly impairs FT eIF-2-alpha phosphorylation in a YEF3-dependent manner; FT when associated with A-757-758-A; A-762; A-765; A-775; FT 777-A-A-778; 782-A-A-783 and 786-A-A-787." FT /evidence="ECO:0000269|PubMed:15722345, FT ECO:0000269|PubMed:22888004" FT MUTAGEN 1444 FT /note="G->D: Decreases interaction with GCN20 and polysomal FT association." FT /evidence="ECO:0000269|PubMed:9234705" FT MUTAGEN 1458 FT /note="E->A: Does not inhibit interaction with GCN20, FT reduces ribosome binding, ribosome binding by GCN20 and FT strongly impairs eIF-2-alpha phosphorylation; when FT associated with 1461-A--A-1465." FT /evidence="ECO:0000269|PubMed:15722345" FT MUTAGEN 1461..1465 FT /note="WRTKR->AAAAA: Does not inhibit interaction with FT GCN20, reduces ribosome binding, ribosome binding by GCN20 FT and strongly impairs eIF-2-alpha phosphorylation; when FT associated with A-1458." FT /evidence="ECO:0000269|PubMed:15722345" FT MUTAGEN 2224 FT /note="N->A: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2227 FT /note="R->A: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2245 FT /note="N->A: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2247 FT /note="K->A: Increased ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2251 FT /note="S->A: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2259 FT /note="R->A: Decreases interaction with GCN2 and YIH1 but FT not with GCN20 and ribosomes." FT /evidence="ECO:0000269|PubMed:11101534, FT ECO:0000269|PubMed:15126500, ECO:0000269|PubMed:21239490, FT ECO:0000269|PubMed:36441697" FT MUTAGEN 2261 FT /note="V->A: Increased ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2261 FT /note="V->D: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2263 FT /note="E->A: Increased ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2264 FT /note="R->A: Increased ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2270 FT /note="K->A: Impaired ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2289 FT /note="R->A: Impaired ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2291 FT /note="F->E: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2291 FT /note="F->L: Does not interact with GCN2, impairs FT eIF-2-alpha phosphorylation and fails to derepress GCN4 FT translation in amino acid-starved cells." FT /evidence="ECO:0000269|PubMed:11350982" FT MUTAGEN 2294 FT /note="Q->A: Increased ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2294 FT /note="Q->D: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2297 FT /note="R->A: Impaired ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2301 FT /note="K->A: Impaired ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2304 FT /note="S->P: Does not interact with GCN2." FT /evidence="ECO:0000269|PubMed:11350982" FT MUTAGEN 2305 FT /note="D->A: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2309 FT /note="E->A: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2330 FT /note="D->A: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2335 FT /note="E->A: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" FT MUTAGEN 2353 FT /note="L->P: Does not interact with GCN2." FT /evidence="ECO:0000269|PubMed:11350982" FT MUTAGEN 2382 FT /note="E->A: Does not affect ability to activate GCN2." FT /evidence="ECO:0000269|PubMed:36441697" SQ SEQUENCE 2672 AA; 296698 MW; 980FDD03753E9D1C CRC64; MTAILNWEDI SPVLEKGTRE SHVSKRVPFL QDISQLVRQE TLEKPQLSEI AFVLLNTFTI YEDNRSKSLV TSILLDILNL EPCLLENFIR FISDVVISNP ATKAVADYLN LLDWINSFLI FVSHNSNLFE EYIPKLLVAH SYATFGVETI LDNQEEGKKS QDKQNQHRKR IRYCIFQTTV KAFLKCLKDN DDSISFMKIS IKTVLESYSK LKITSVGVVM IMGALTQAAL QLLSRQPALH SVLKENSAEK YCEYLGKEVF LGKNPPSSFC LEIGLKPFLK EFVSQELFIK FFIPNIEKAV LRSPEVGFSI LSELYAGVSP EKVNLLNAFA SSKLINQYFS SFKSSKEVVR SVSLQSMIIL LRKISNTDTT LEDLTKLIDE IFKNIKSNLN ADYKSLISKI LIEIPLTHYE VSEKICKGLS PYIGKEGNEA ALTLMLNAFF VHYFSLGKPI EDLDKIISAG FADKKPALKK CWFAAFLNNS NAASEEVILN FIDGCLEFVK DSIIHYQTHG HACILASIEF TNKILALDNT ELNDRVMQLI ETLPENSSIG DAILTAALST ELSIENRIHA VNLLQELFYK KPEFIGFSVI DAIERRMRVQ ELIPQQNTSF KYVTSVLLAI TSELPDKEAS IKVLINALVI AQWNIFNIKN GWAGLVLRAR LDPAEVVKEH ASVIMEKILE ITGSCEWIDT IYGACGLQAA AYAAFIQPNE FTPILCKTIE ADLTADDFSR LSEEDFEIFA GEEGVLVVDV LEESMNKKLS NKNSKEYETL MWEQKIRKEQ AKKNVKKLSK EEQELVNEQL AKESAVRSHV SEISTRLKRG IRLVSELSKA ACLVQNGIAT WFPLAVTKLL YLCSEPNISK LTEDVNNVFL QLSQNVSERL GNIRLFLGLA TLRVHNANGI SQDYLQEPLV ELLTRVLFRI KFVSNQAAID SISLTYILPL LINVLEKGKA IALKNADKPV VKAEFVEEDE EEEHLLLAME IISVHAEAFE DPSIPRISIV EVLLSLLSLP SKAKIAKDCF NALCQSISVA PNQEDLDMIL SNLLSPNQFV RSTILETLDN EFELEPFMKY SPEVFICRFD SDPSNREIAD FIWEFNKFVV NDELLKSLFP LFNQDDSGLR LFAANAYAFG AVSLFTSEEN SSKDYLNDLL NFYKEKAKPL EPILDQFGLV LVSASEQKDP WQGRSTVAIT LKIMAKAFSA EDDTVVNIIK FLVDDGGLVD REPIVRQEMK EAGVELITLH GSQNSKDLIP IFEEALSSST DSALKENVII LYGTLARHLQ QSDARIHTII ERLLSTLDTP SADIQQAVSA CIAPLVFQFK QKVGDYLGIL MEKLLNPTVA SSMRKGAAWG IAGLVKGYGI SALSEFDIIR NLIEAAEDKK EPKRRESVGF CFQYLSESLG KFFEPYVIEI LPNILKNLGD AVPEVRDATA RATKAIMAHT TGYGVKKLIP VAVSNLDEIA WRTKRGSVQL LGNMAYLDPT QLSASLSTIV PEIVGVLNDS HKEVRKAADE SLKRFGEVIR NPEIQKLVPV LLQAIGDPTK YTEEALDSLI QTQFVHYIDG PSLALIIHII HRGMHDRSAN IKRKACKIVG NMAILVDTKD LIPYLQQLID EVEIAMVDPV PNTRATAARA LGALVERLGE EQFPDLIPRL LDTLSDESKS GDRLGSAQAL AEVISGLGLT KLDEMLPTIL AGVTNFRAYI REGFMPLLLF LPVCFGSQFA PYINQIIQPI LSGLADNDEN IRDTALKAGK LIVKNYATKA VDLLLPELER GMFDENDRIR LSSVQLTGEL LFQVTGISSR NEFSEEDGDH NGEFSGKLVD VLGQDRRDRI LAALFVCRND TSGIVRATTV DIWKALVPNT PRAVKEILPT LTGMIVTHLA SSSNVLRNIA AQTLGDLVRR VGGNALSQLL PSLEESLIET SNSDSRQGVC IALYELIESA STETISQFQS TIVNIIRTAL IDESATVREA AALSFDVFQD VVGKTAVDEV LPYLLHMLES SDNSDFALLG LQEIMSKKSD VIFPILIPTL LAPPIDAFRA SALGSLAEVA GSALYKRLSI IINALVDAII GTSEDESTKG ALELALDRVF LSVNDDEGLH PLLQQIMSLL KSDNIEKRIA VLERLPNFFD KTVLDFDVYI PNFVSHAILS LDDEDQRVVN GNFNALSTLL KKVDKPTLEK LVKPAKQSLA LTGRQGQDVA AFKLPRGPNC VLPIFLHGLM YGSNDEREES ALAIADVVSK TPAANLKPFV SVITGPLIRV VGERFSSDIK AAILFALNVL FIKIPMFLRP FIPQLQRTFV KSLSDATNET LRLRAAKALG ALIEHQPRVD PLVIELVTGA KQATDEGVKT AMLKALLEVI MKAGSKLNEN SKTNIVNLVE EEMLGSNDKL AVAYAKLIGS LSEILSNDEA HKILQDKVLN ADLDGETGKF AILTLNSFLK DAPTHIFNTG LIDEFVSYIL NAIRSPDVYF GENGTIAAGK LLLLEGEKRS PFVKKDAAEP FKIGDENINL LINELSKAVL QPASNSTDVR RLALVVIRTL ARFKFDECIK QYFDVVGPSV FSCLRDPVIP IKLAAEKAYL ALFKLVEEDD MHTFNEWFAK ISDRGNSIET VTGTTIQLRS VGDYTKRVGK RLANVERERI AAGGDAETMF SDRFEDEREI WAVGGVELTT DI //