GCN1_YEAST
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 03-AUG-2022, entry version 187.
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:0000312|SGD:S000003163}; OrderedLocusNames=YGL195W;
GN 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;
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;
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).
CC -!- FUNCTION: Acts as a positive activator of the GCN2 protein kinase
CC activity in response to low amino acid, carbon, or purine availability
CC (PubMed:8497269, PubMed:24333428. PubMed:10733573). Component of the
CC GCN1-GCN20 complex that forms a complex with GCN2 on translating
CC ribosomes; during this process, GCN1 seems to act as a chaperone to
CC facilitate delivery of uncharged tRNAs that enter the A site of
CC ribosomes to the tRNA-binding domain of GCN2, and hence stimulating
CC GCN2 kinase activity (PubMed:7621831, PubMed:9234705, PubMed:15722345).
CC Participates in the repression of global protein synthesis and in gene-
CC specific mRNA translation activation, such as the transcriptional
CC activator GCN4, by promoting the GCN2-mediated phosphorylation of
CC eukaryotic translation initiation factor 2 (eIF-2-alpha/SUI2) on 'Ser-
CC 52', and hence allowing GCN4-mediated reprogramming of amino acid
CC biosynthetic gene expression to alleviate nutrient depletion
CC (PubMed:8497269, PubMed:10801780, PubMed:11350982, PubMed:15722345).
CC {ECO:0000269|PubMed:10733573, ECO:0000269|PubMed:10801780,
CC ECO:0000269|PubMed:11350982, ECO:0000269|PubMed:15722345,
CC ECO:0000269|PubMed:24333428, 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:11101534, PubMed:10801780, PubMed:11350982,
CC PubMed:15126500, PubMed:15722345, PubMed:21849502). Interacts (via C-
CC terminus) with GCN20 (via N-terminus); this interaction stimulates GCN2
CC kinase activity in response to amino acid starvation (PubMed:7621831,
CC PubMed:9234705, PubMed:11101534). The GCN1-GCN20 complex interacts with
CC GCN2 on translating ribosomes in amino acid-starved cells; GCN1 may
CC bind near the ribosomal A-site and promotes the transfer of uncharged
CC tRNAs from the A-site to the tRNA-binding domain in GCN2 for its
CC subsequent kinase activation, and hence allowing GCN4 translational
CC activation and derepression of amino acid biosynthetic genes
CC (PubMed:7621831, PubMed:9234705, PubMed:10775272, PubMed:11101534).
CC Interacts (via C-terminus) with YIH1 (via N-terminus); this interaction
CC reduces the GCN1-GCN20 complex formation and prevents the interaction
CC of GCN1 with GCN2 and GCN2 kinase activation in amino acid-starved
CC cells (PubMed:15126500, PubMed:21239490, PubMed:22404850). Interacts
CC with GIR2; this interaction prevents the interaction of GCN1 with GCN2
CC 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:7621831, PubMed:9234705, PubMed:11101534, PubMed:15722345,
CC PubMed:19448108, PubMed:21849502, PubMed:22888004, PubMed:25437641).
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:7621831, ECO:0000269|PubMed:9234705}.
CC -!- INTERACTION:
CC P33892; P43535: GCN20; NbExp=3; 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 -!- 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}.
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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 AlphaFoldDB; P33892; -.
DR BioGRID; 33062; 483.
DR ComplexPortal; CPX-1808; GCN1-GCN20 complex.
DR DIP; DIP-2344N; -.
DR IntAct; P33892; 134.
DR MINT; P33892; -.
DR STRING; 4932.YGL195W; -.
DR iPTMnet; P33892; -.
DR MaxQB; P33892; -.
DR PaxDb; P33892; -.
DR PRIDE; P33892; -.
DR EnsemblFungi; YGL195W_mRNA; YGL195W; YGL195W.
DR GeneID; 852680; -.
DR KEGG; sce:YGL195W; -.
DR SGD; S000003163; GCN1.
DR VEuPathDB; FungiDB:YGL195W; -.
DR eggNOG; KOG1242; Eukaryota.
DR GeneTree; ENSGT00940000153612; -.
DR HOGENOM; CLU_000504_2_0_1; -.
DR InParanoid; P33892; -.
DR OMA; LQWINAF; -.
DR BioCyc; YEAST:G3O-30676-MON; -.
DR PRO; PR:P33892; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P33892; protein.
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:0042788; C:polysomal ribosome; IDA:UniProtKB.
DR GO; GO:0005844; C:polysome; IDA:UniProtKB.
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:0043022; F:ribosome binding; IDA:UniProtKB.
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:0072755; P:cellular response to benomyl; IMP:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:UniProtKB.
DR GO; GO:1990451; P:cellular stress response to acidic pH; IMP:UniProtKB.
DR GO; GO:0140469; P:GCN2-mediated signaling; IMP:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:SGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; IMP:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IDA:SGD.
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:0006417; P:regulation of translation; IBA:GO_Central.
DR GO; GO:0006448; P:regulation of translational elongation; IMP:SGD.
DR Gene3D; 1.25.10.10; -; 6.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR033173; Gcn1.
DR InterPro; IPR022716; Gcn1_N.
DR InterPro; IPR021133; HEAT_type_2.
DR InterPro; IPR034085; TOG.
DR PANTHER; PTHR23346:SF7; PTHR23346:SF7; 1.
DR Pfam; PF12074; Gcn1_N; 2.
DR SMART; SM01349; TOG; 1.
DR SUPFAM; SSF48371; SSF48371; 4.
DR PROSITE; PS50077; HEAT_REPEAT; 4.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; Reference proteome; Repeat; Stress response;
KW 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 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; 782-
FT 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; 777-A-A-
FT 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; 777-A-A-
FT 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; 777-A-A-
FT 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; 782-
FT 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; 777-
FT 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; 777-
FT 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; 777-
FT 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 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 MUTAGEN 2291
FT /note="F->L: Does not interact with GCN2, impairs eIF-2-
FT alpha phosphorylation and fails to derepress GCN4
FT translation in amino acid-starved cells."
FT /evidence="ECO:0000269|PubMed:11350982"
FT MUTAGEN 2304
FT /note="S->P: Does not interact with GCN2."
FT /evidence="ECO:0000269|PubMed:11350982"
FT MUTAGEN 2353
FT /note="L->P: Does not interact with GCN2."
FT /evidence="ECO:0000269|PubMed:11350982"
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
