GCN2_YEAST
ID GCN2_YEAST Reviewed; 1659 AA.
AC P15442; D6VSR3;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 3.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=eIF-2-alpha kinase GCN2 {ECO:0000250|UniProtKB:Q9HGN1};
DE EC=2.7.11.1 {ECO:0000269|PubMed:10983975, ECO:0000269|PubMed:17202131, ECO:0000269|PubMed:2188100, ECO:0000269|PubMed:7623840, ECO:0000269|PubMed:8798780};
DE AltName: Full=General control non-derepressible protein 2 {ECO:0000312|SGD:S000002691};
DE AltName: Full=Serine/threonine-protein kinase GCN2 {ECO:0000305};
GN Name=GCN2 {ECO:0000312|SGD:S000002691};
GN Synonyms=AAS1 {ECO:0000312|SGD:S000002691}; OrderedLocusNames=YDR283C;
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], FUNCTION, AND MUTAGENESIS OF LYS-628 AND
RP LYS-629.
RX PubMed=2660141; DOI=10.1073/pnas.86.12.4579;
RA Wek R.C., Jackson B.M., Hinnebusch A.G.;
RT "Juxtaposition of domains homologous to protein kinases and histidyl-tRNA
RT synthetases in GCN2 protein suggests a mechanism for coupling GCN4
RT expression to amino acid availability.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4579-4583(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-1481.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=3290651; DOI=10.1128/mcb.8.5.2132-2139.1988;
RA Roussou I., Thireos G., Hauge B.M.;
RT "Transcriptional-translational regulatory circuit in Saccharomyces
RT cerevisiae which involves the GCN4 transcriptional activator and the GCN2
RT protein kinase.";
RL Mol. Cell. Biol. 8:2132-2139(1988).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF
RP GLU-601; LYS-628; GLU-821 AND GLU-1606.
RX PubMed=2188100; DOI=10.1128/mcb.10.6.2820-2831.1990;
RA Wek R.C., Ramirez M., Jackson B.M., Hinnebusch A.G.;
RT "Identification of positive-acting domains in GCN2 protein kinase required
RT for translational activation of GCN4 expression.";
RL Mol. Cell. Biol. 10:2820-2831(1990).
RN [6]
RP ASSOCIATION WITH RIBOSOMES, AUTOPHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=2038314; DOI=10.1128/mcb.11.6.3027-3036.1991;
RA Ramirez M., Wek R.C., Hinnebusch A.G.;
RT "Ribosome association of GCN2 protein kinase, a translational activator of
RT the GCN4 gene of Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 11:3027-3036(1991).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF LYS-628.
RX PubMed=1739968; DOI=10.1016/0092-8674(92)90193-g;
RA Dever T.E., Feng L., Wek R.C., Cigan A.M., Donahue T.F., Hinnebusch A.G.;
RT "Phosphorylation of initiation factor 2 alpha by protein kinase GCN2
RT mediates gene-specific translational control of GCN4 in yeast.";
RL Cell 68:585-596(1992).
RN [8]
RP MUTAGENESIS OF SER-582; PHE-716; MET-788; GLU-803; GLU-821; HIS-861;
RP PHE-1134; ASP-1138; ALA-1197; HIS-1308; GLY-1338; ARG-1557; GLU-1591 AND
RP GLU-1606.
RX PubMed=1448107; DOI=10.1128/mcb.12.12.5801-5815.1992;
RA Ramirez M., Wek R.C., Vazquez de Aldana C.R., Jackson B.M., Freeman B.,
RA Hinnebusch A.G.;
RT "Mutations activating the yeast eIF-2 alpha kinase GCN2: isolation of
RT alleles altering the domain related to histidyl-tRNA synthetases.";
RL Mol. Cell. Biol. 12:5801-5815(1992).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8336737; DOI=10.1128/mcb.13.8.5099-5111.1993;
RA Rolfes R.J., Hinnebusch A.G.;
RT "Translation of the yeast transcriptional activator GCN4 is stimulated by
RT purine limitation: implications for activation of the protein kinase
RT GCN2.";
RL Mol. Cell. Biol. 13:5099-5111(1993).
RN [10]
RP FUNCTION.
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 [11]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TRNA-BINDING, DOMAIN,
RP AND MUTAGENESIS OF TYR-1119 AND ARG-1120.
RX PubMed=7623840; DOI=10.1128/mcb.15.8.4497;
RA Wek S.A., Zhu S., Wek R.C.;
RT "The histidyl-tRNA synthetase-related sequence in the eIF-2 alpha protein
RT kinase GCN2 interacts with tRNA and is required for activation in response
RT to starvation for different amino acids.";
RL Mol. Cell. Biol. 15:4497-4506(1995).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, DOMAIN, AND MUTAGENESIS
RP OF LYS-628; TYR-1119 AND ARG-1120.
RX PubMed=8798780; DOI=10.1074/jbc.271.40.24989;
RA Zhu S., Sobolev A.Y., Wek R.C.;
RT "Histidyl-tRNA synthetase-related sequences in GCN2 protein kinase regulate
RT in vitro phosphorylation of eIF-2.";
RL J. Biol. Chem. 271:24989-24994(1996).
RN [13]
RP FUNCTION, ASSOCIATION WITH RIBOSOMES, DOMAIN, AND MUTAGENESIS OF TYR-1119;
RP ARG-1120 AND 1552-LYS--LYS-1556.
RX PubMed=9430731; DOI=10.1074/jbc.273.3.1808;
RA Zhu S., Wek R.C.;
RT "Ribosome-binding domain of eukaryotic initiation factor-2 kinase GCN2
RT facilitates translation control.";
RL J. Biol. Chem. 273:1808-1814(1998).
RN [14]
RP FUNCTION, PHOSPHORYLATION AT THR-882 AND THR-887, AND MUTAGENESIS OF
RP THR-882 AND THR-887.
RX PubMed=9528799; DOI=10.1128/mcb.18.4.2282;
RA Romano P.R., Garcia-Barrio M.T., Zhang X., Wang Q., Taylor D.R., Zhang F.,
RA Herring C., Mathews M.B., Qin J., Hinnebusch A.G.;
RT "Autophosphorylation in the activation loop is required for full kinase
RT activity in vivo of human and yeast eukaryotic initiation factor 2alpha
RT kinases PKR and GCN2.";
RL Mol. Cell. Biol. 18:2282-2297(1998).
RN [15]
RP SUBUNIT, AND DOMAIN.
RX PubMed=9566889; DOI=10.1128/mcb.18.5.2697;
RA Qiu H., Garcia-Barrio M.T., Hinnebusch A.G.;
RT "Dimerization by translation initiation factor 2 kinase GCN2 is mediated by
RT interactions in the C-terminal ribosome-binding region and the protein
RT kinase domain.";
RL Mol. Cell. Biol. 18:2697-2711(1998).
RN [16]
RP INTERACTION WITH GCN1, AND IDENTIFICATION IN A COMPLEX WITH GCN1 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 [17]
RP INTERACTION WITH GCN1, AND IDENTIFICATION IN A COMPLEX WITH GCN1 AND GCN20.
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 [18]
RP FUNCTION, INTERACTION WITH GCN1, AND MUTAGENESIS OF TYR-74.
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 [19]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, TRNA-BINDING, ASSOCIATION WITH
RP RIBOSOMES, AUTOPHOSPHORYLATION, DOMAIN, AND MUTAGENESIS OF LYS-628;
RP GLU-803; TYR-1119; ARG-1120; LYS-1552; LYS-1553 AND LYS-1556.
RX PubMed=10983975; DOI=10.1016/s1097-2765(00)00028-9;
RA Dong J., Qiu H., Garcia-Barrio M., Anderson J., Hinnebusch A.G.;
RT "Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from
RT a bipartite tRNA-binding domain.";
RL Mol. Cell 6:269-279(2000).
RN [20]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-628.
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 [21]
RP SUBUNIT, DOMAIN, AND MUTAGENESIS OF VAL-1080; LEU-1088 AND LEU-1090.
RX PubMed=11250908; DOI=10.1093/emboj/20.6.1425;
RA Qiu H., Dong J., Hu C., Francklyn C.S., Hinnebusch A.G.;
RT "The tRNA-binding moiety in GCN2 contains a dimerization domain that
RT interacts with the kinase domain and is required for tRNA binding and
RT kinase activation.";
RL EMBO J. 20:1425-1438(2001).
RN [22]
RP FUNCTION, INTERACTION WITH GCN1, AND MUTAGENESIS OF TYR-74.
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 [23]
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 [24]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, AUTOPHOSPHORYLATION, AND
RP MUTAGENESIS OF ARG-594; ASP-598 AND LYS-628.
RX PubMed=17202131; DOI=10.1074/jbc.m607897200;
RA Dey M., Cao C., Sicheri F., Dever T.E.;
RT "Conserved intermolecular salt bridge required for activation of protein
RT kinases PKR, GCN2, and PERK.";
RL J. Biol. Chem. 282:6653-6660(2007).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-761, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [27]
RP INTERACTION WITH GCN1 AND TIF11, AND MUTAGENESIS OF LYS-1552; LYS-1553 AND
RP LYS-1556.
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 [28]
RP ASSOCIATION WITH RIBOSOMES.
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 [29]
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 [30]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 594-664 AND 768-997 OF WILD-TYPE
RP AND MUTANTS GLY-794 AND ASN-835 IN COMPLEX WITH ATP, AND SUBUNIT.
RX PubMed=15964839; DOI=10.1074/jbc.m504096200;
RA Padyana A.K., Qiu H., Roll-Mecak A., Hinnebusch A.G., Burley S.K.;
RT "Structural basis for autoinhibition and mutational activation of
RT eukaryotic initiation factor 2alpha protein kinase GCN2.";
RL J. Biol. Chem. 280:29289-29299(2005).
CC -!- FUNCTION: Metabolic-stress sensing protein kinase that phosphorylates
CC the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-
CC alpha/SUI2) on 'Ser-52' in response to low amino acid, carbon, or
CC purine availability (PubMed:1739968, PubMed:7623840, PubMed:8798780,
CC PubMed:9528799, PubMed:10983975, PubMed:17202131, PubMed:8336737,
CC PubMed:10733573). Plays a role as an activator of the general amino
CC acid control (GAAC) pathway required for adapatation to nutrient
CC starvation. Converts phosphorylated eIF-2-alpha/SUI2 either to a
CC competitive inhibitor of translation initiation factor eIF-2B, leading
CC to a global protein synthesis repression, and thus to a reduced overall
CC utilization of amino acids, or to a translational initiation activation
CC of specific mRNAs, such as the transcriptional activator GCN4, and
CC hence allowing GCN4-mediated reprogramming of transcription to
CC alleviate nutrient depletion (PubMed:2660141, PubMed:2188100,
CC PubMed:1739968, PubMed:7621831, PubMed:7623840, PubMed:8798780,
CC PubMed:10801780, PubMed:11350982, PubMed:24333428, PubMed:10733573).
CC Binds uncharged tRNAs (PubMed:7623840, PubMed:10983975).
CC {ECO:0000269|PubMed:10733573, ECO:0000269|PubMed:10801780,
CC ECO:0000269|PubMed:10983975, ECO:0000269|PubMed:11350982,
CC ECO:0000269|PubMed:17202131, ECO:0000269|PubMed:1739968,
CC ECO:0000269|PubMed:2188100, ECO:0000269|PubMed:24333428,
CC ECO:0000269|PubMed:2660141, ECO:0000269|PubMed:7621831,
CC ECO:0000269|PubMed:7623840, ECO:0000269|PubMed:8336737,
CC ECO:0000269|PubMed:8798780, ECO:0000269|PubMed:9430731,
CC ECO:0000269|PubMed:9528799}.
CC -!- FUNCTION: (orthologuous-specific) Binds to aminoacylated tRNA(Phe) less
CC tightly than to deacylated tRNA(Phe) (PubMed:10983975). Binds to
CC double-stranded RNA (PubMed:9430731). {ECO:0000269|PubMed:10983975,
CC ECO:0000269|PubMed:9430731}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:10983975, ECO:0000269|PubMed:17202131,
CC ECO:0000269|PubMed:2188100, ECO:0000269|PubMed:7623840,
CC ECO:0000269|PubMed:8798780};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:10983975,
CC ECO:0000269|PubMed:17202131, ECO:0000269|PubMed:2188100,
CC ECO:0000269|PubMed:7623840, ECO:0000269|PubMed:8798780};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:17202131};
CC -!- ACTIVITY REGULATION: The kinase activity is stimulated upon binding to
CC uncharged tRNAs (PubMed:7623840). {ECO:0000269|PubMed:7623840}.
CC -!- SUBUNIT: Homodimer; homodimerization is important for kinase activation
CC by uncharged tRNAs (PubMed:9566889, PubMed:10983975, PubMed:11250908,
CC PubMed:17202131, PubMed:15964839). Interacts (via N-terminal RWD
CC domain) with GCN1 (via N- and C-terminus); this interaction stimulates
CC GCN2 kinase activity in a GCN20-dependent manner in response to amino
CC acid starvation (PubMed:10775272, PubMed:11101534, PubMed:10801780,
CC PubMed:11350982, PubMed:21849502). Interacts (via N-terminus) with the
CC GCN1-GCN20 complex on translating ribosomes in amino acid-starved
CC cells; GCN1 may bind near the ribosomal A-site and promotes the
CC transfer of uncharged tRNAs from the A-site to the tRNA-binding domain
CC in GCN2 for its subsequent kinase activation, and hence allowing GCN4
CC translational activation and derepression of amino acid biosynthetic
CC genes (PubMed:10775272, PubMed:11101534). Interacts (via C-terminus)
CC with TIF11; this interaction is direct, occurs in amino acid-repleted
CC cells, may be stabilzed in a ribosome-dependent manner, reduces GCN2-
CC mediated eIF-2-alpha phosphorylation but not GCN2 autophosphorylation
CC and is lost in amino acid-starved cells and by uncharged tRNAs
CC (PubMed:21849502). Associates (via C-terminus) with ribosomes
CC (PubMed:2038314, PubMed:9430731, PubMed:10983975, PubMed:22888004).
CC {ECO:0000269|PubMed:10775272, ECO:0000269|PubMed:10801780,
CC ECO:0000269|PubMed:10983975, ECO:0000269|PubMed:11101534,
CC ECO:0000269|PubMed:11250908, ECO:0000269|PubMed:11350982,
CC ECO:0000269|PubMed:15964839, ECO:0000269|PubMed:17202131,
CC ECO:0000269|PubMed:2038314, ECO:0000269|PubMed:21849502,
CC ECO:0000269|PubMed:22888004, ECO:0000269|PubMed:9430731,
CC ECO:0000269|PubMed:9566889}.
CC -!- INTERACTION:
CC P15442; P29295: HRR25; NbExp=5; IntAct=EBI-330, EBI-8536;
CC P15442; P22211: NPR1; NbExp=2; IntAct=EBI-330, EBI-12207;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:2038314}.
CC -!- DOMAIN: The C-terminal domain negatively regulates kinase activity via
CC an autoinhibitory association with the protein kinase and histidyl-tRNA
CC synthetase-like domains in amino acid-repleted cells, that is
CC counteracted by uncharged tRNAs in amino acid-starved cells
CC (PubMed:7623840, PubMed:8798780, PubMed:10983975, PubMed:11250908). The
CC C-terminal, histidyl-tRNA synthetase-like region and protein kinase
CC domains are necessary for homodimer formation (PubMed:9566889,
CC PubMed:10983975, PubMed:11250908). The C-terminal and protein kinase
CC domains are necessary for ribosome association (PubMed:9566889,
CC PubMed:10983975). The C-terminal and histidyl-tRNA synthetase-like
CC regions are required for uncharged tRNAs binding in amino acid-starved
CC cells (PubMed:7623840, PubMed:8798780, PubMed:9430731,
CC PubMed:10983975). {ECO:0000269|PubMed:10983975,
CC ECO:0000269|PubMed:11250908, ECO:0000269|PubMed:7623840,
CC ECO:0000269|PubMed:8798780, ECO:0000269|PubMed:9430731,
CC ECO:0000269|PubMed:9566889}.
CC -!- PTM: Autophosphorylated, autophosphorylation on Thr-882 and Thr-887
CC increases kinase activity. {ECO:0000269|PubMed:10983975,
CC ECO:0000269|PubMed:17202131, ECO:0000269|PubMed:2038314,
CC ECO:0000269|PubMed:2188100, ECO:0000269|PubMed:8798780,
CC ECO:0000269|PubMed:9528799}.
CC -!- DISRUPTION PHENOTYPE: Abolishes phosphorylation of the alpha subunit of
CC eukaryotic translation initiation factor 2 (eIF-2-alpha/SUI2) during
CC amino acid, purine, and glucose starvation (PubMed:8336737,
CC PubMed:10733573). Inhibits GCN4 derepression in glucose, amino acid, or
CC purine-starved cells (PubMed:8336737, PubMed:10733573). Decreases
CC vacuolar free amino acid levels during glucose starvation
CC (PubMed:10733573). Sensitive to the purine analog 8-azaadenine
CC (PubMed:8336737). Increases duration of lag phase on return to glucose-
CC rich medium following glucose starvation (PubMed:10733573).
CC {ECO:0000269|PubMed:10733573, ECO:0000269|PubMed:8336737}.
CC -!- MISCELLANEOUS: Present with 279 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. GCN2 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA34636.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAA34881.1; Type=Frameshift; Evidence={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; M27082; AAA34636.1; ALT_INIT; Genomic_DNA.
DR EMBL; U51030; AAB64461.1; -; Genomic_DNA.
DR EMBL; M20487; AAA34881.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BK006938; DAA12123.1; -; Genomic_DNA.
DR PIR; S70139; OKBYN2.
DR RefSeq; NP_010569.3; NM_001180591.3.
DR PDB; 1ZXE; X-ray; 2.60 A; A/B/C/D/E/F=594-997.
DR PDB; 1ZY4; X-ray; 1.95 A; A/B=594-997.
DR PDB; 1ZY5; X-ray; 2.00 A; A/B=594-997.
DR PDB; 1ZYC; X-ray; 3.00 A; A/B/C/D=594-997.
DR PDB; 1ZYD; X-ray; 2.75 A; A/B=594-997.
DR PDB; 2YZ0; NMR; -; A=1-138.
DR PDB; 4OTM; X-ray; 1.95 A; A/B=1519-1659.
DR PDBsum; 1ZXE; -.
DR PDBsum; 1ZY4; -.
DR PDBsum; 1ZY5; -.
DR PDBsum; 1ZYC; -.
DR PDBsum; 1ZYD; -.
DR PDBsum; 2YZ0; -.
DR PDBsum; 4OTM; -.
DR AlphaFoldDB; P15442; -.
DR SMR; P15442; -.
DR BioGRID; 32336; 240.
DR DIP; DIP-2346N; -.
DR IntAct; P15442; 27.
DR MINT; P15442; -.
DR STRING; 4932.YDR283C; -.
DR iPTMnet; P15442; -.
DR MaxQB; P15442; -.
DR PaxDb; P15442; -.
DR PRIDE; P15442; -.
DR EnsemblFungi; YDR283C_mRNA; YDR283C; YDR283C.
DR GeneID; 851877; -.
DR KEGG; sce:YDR283C; -.
DR SGD; S000002691; GCN2.
DR VEuPathDB; FungiDB:YDR283C; -.
DR eggNOG; KOG1035; Eukaryota.
DR GeneTree; ENSGT00940000158121; -.
DR HOGENOM; CLU_001222_2_0_1; -.
DR InParanoid; P15442; -.
DR OMA; GSEMIYE; -.
DR BioCyc; YEAST:G3O-29848-MON; -.
DR BRENDA; 2.7.11.20; 984.
DR EvolutionaryTrace; P15442; -.
DR PRO; PR:P15442; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P15442; protein.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0022626; C:cytosolic ribosome; IDA:SGD.
DR GO; GO:0015934; C:large ribosomal subunit; IDA:UniProtKB.
DR GO; GO:0042788; C:polysomal ribosome; IDA:UniProtKB.
DR GO; GO:0015935; C:small ribosomal subunit; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0004694; F:eukaryotic translation initiation factor 2alpha kinase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IMP:CACAO.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0043023; F:ribosomal large subunit binding; IDA:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0031369; F:translation initiation factor binding; IPI:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IDA: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:0071232; P:cellular response to histidine; IDA: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:0000077; P:DNA damage checkpoint signaling; IMP:SGD.
DR GO; GO:0140469; P:GCN2-mediated signaling; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:UniProtKB.
DR GO; GO:0100002; P:negative regulation of protein kinase activity by protein phosphorylation; IDA:SGD.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:SGD.
DR GO; GO:1903833; P:positive regulation of cellular response to amino acid starvation; IDA:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IDA:SGD.
DR GO; GO:0071264; P:positive regulation of translational initiation in response to starvation; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IEA:UniProt.
DR GO; GO:0006446; P:regulation of translational initiation; IDA:UniProtKB.
DR GO; GO:0006412; P:translation; IEA:UniProtKB-KW.
DR CDD; cd00773; HisRS-like_core; 1.
DR Gene3D; 3.10.110.10; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR Gene3D; 3.40.50.800; -; 1.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR036621; Anticodon-bd_dom_sf.
DR InterPro; IPR016255; Gcn2.
DR InterPro; IPR041715; HisRS-like_core.
DR InterPro; IPR024435; HisRS-related_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR006575; RWD-domain.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF12745; HGTP_anticodon2; 1.
DR Pfam; PF00069; Pkinase; 3.
DR Pfam; PF05773; RWD; 1.
DR Pfam; PF13393; tRNA-synt_His; 1.
DR PIRSF; PIRSF000660; Ser/Thr_PK_GCN2; 1.
DR SMART; SM00591; RWD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR SUPFAM; SSF56112; SSF56112; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50908; RWD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; ATP-binding; Cytoplasm; Kinase;
KW Nucleotide-binding; Phosphoprotein; Protein biosynthesis;
KW Reference proteome; Repeat; RNA-binding; Serine/threonine-protein kinase;
KW Stress response; Transferase; Translation regulation; tRNA-binding.
FT CHAIN 1..1659
FT /note="eIF-2-alpha kinase GCN2"
FT /id="PRO_0000085963"
FT DOMAIN 17..128
FT /note="RWD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00179"
FT DOMAIN 256..527
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 599..981
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 149..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 671..691
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 727..768
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 999..1519
FT /note="Histidyl-tRNA synthetase-like"
FT COMPBIAS 728..744
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 835
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9BRS2"
FT BINDING 605..613
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 628
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 761
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358"
FT MOD_RES 882
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:9528799"
FT MOD_RES 887
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:9528799"
FT MUTAGEN 74
FT /note="Y->A: Inhibits interaction with GCN1, eIF-2-alpha
FT phosphorylation and fails to derepress GCN4 translation in
FT amino acid-starved cells."
FT /evidence="ECO:0000269|PubMed:10801780,
FT ECO:0000269|PubMed:11350982"
FT MUTAGEN 582
FT /note="S->F: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 594
FT /note="R->D: Inhibits autophosphorylation, eIF-2-alpha
FT kinase activity and derepression of GCN4 translation.
FT Restores eIF-2-alpha kinase activity and derepression of
FT GCN4, but not autophosphorylation; when associated with R-
FT 598."
FT /evidence="ECO:0000269|PubMed:17202131"
FT MUTAGEN 598
FT /note="D->R: Inhibits autophosphorylation, eIF-2-alpha
FT kinase activity and derepression of GCN4 translation.
FT Restores eIF-2-alpha kinase activity and derepression of
FT GCN4, but not autophosphorylation; when associated with D-
FT 594."
FT /evidence="ECO:0000269|PubMed:17202131"
FT MUTAGEN 601
FT /note="E->K: Increases the constitutive kinase activity in
FT absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:2188100"
FT MUTAGEN 628
FT /note="K->V,R: Inhibits autophosphorylation, eIF-2-alpha
FT kinase activity and derepression of GCN4 translation in
FT amino acid-starved cells."
FT /evidence="ECO:0000269|PubMed:10733573,
FT ECO:0000269|PubMed:10983975, ECO:0000269|PubMed:17202131,
FT ECO:0000269|PubMed:1739968, ECO:0000269|PubMed:2188100,
FT ECO:0000269|PubMed:2660141, ECO:0000269|PubMed:8798780"
FT MUTAGEN 629
FT /note="K->A: Does not abolish derepression of GCN4
FT translation and amino acid biosynthetic genes in amino
FT acid-starved cells."
FT /evidence="ECO:0000269|PubMed:2660141"
FT MUTAGEN 716
FT /note="F->S: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 788
FT /note="M->V: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 794
FT /note="R->G: Constitutively active allele, bypass the tRNA
FT binding-requirement for kinase activity."
FT /evidence="ECO:0000269|PubMed:15964839"
FT MUTAGEN 803
FT /note="E->V: Increases tRNA binding and the constitutive
FT kinase activity and induces derepression of GCN4
FT translation and amino acid biosynthetic genes in absence of
FT amino acid starvation."
FT /evidence="ECO:0000269|PubMed:10983975,
FT ECO:0000269|PubMed:1448107"
FT MUTAGEN 821
FT /note="E->K: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107,
FT ECO:0000269|PubMed:2188100"
FT MUTAGEN 835
FT /note="D->N: Loss of function."
FT /evidence="ECO:0000269|PubMed:15964839"
FT MUTAGEN 861
FT /note="H->Y: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 882
FT /note="T->A,E,D: Partially impairs kinase activity."
FT /evidence="ECO:0000269|PubMed:9528799"
FT MUTAGEN 882
FT /note="T->S: No effect."
FT /evidence="ECO:0000269|PubMed:9528799"
FT MUTAGEN 887
FT /note="T->A,E,D: Completely abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:9528799"
FT MUTAGEN 887
FT /note="T->S: Partially impairs kinase activity."
FT /evidence="ECO:0000269|PubMed:9528799"
FT MUTAGEN 1080
FT /note="V->A: Inhibits dimerization; when associated with A-
FT 1088 and A-1090."
FT /evidence="ECO:0000269|PubMed:11250908"
FT MUTAGEN 1088
FT /note="L->A: Inhibits dimerization; when associated with A-
FT 1080 and A-1090."
FT /evidence="ECO:0000269|PubMed:11250908"
FT MUTAGEN 1090
FT /note="L->A: Inhibits dimerization; when associated with A-
FT 1080 and A-1088."
FT /evidence="ECO:0000269|PubMed:11250908"
FT MUTAGEN 1119
FT /note="Y->L: Inhibits binding to uncharged tRNAs, decreases
FT eIF-2-alpha kinase activity and derepression of GCN4
FT translation and amino acid biosynthetic genes in amino
FT acid-starved cells; when associated with L-1120."
FT /evidence="ECO:0000269|PubMed:10983975,
FT ECO:0000269|PubMed:7623840, ECO:0000269|PubMed:8798780"
FT MUTAGEN 1120
FT /note="R->L: Inhibits binding to uncharged tRNAs, decreases
FT eIF-2-alpha kinase activity and derepression of GCN4
FT translation and amino acid biosynthetic genes in amino
FT acid-starved cells; when associated with L-1119."
FT /evidence="ECO:0000269|PubMed:10983975,
FT ECO:0000269|PubMed:7623840, ECO:0000269|PubMed:8798780"
FT MUTAGEN 1134
FT /note="F->L: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 1138
FT /note="D->N: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 1197
FT /note="A->G: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 1308
FT /note="H->Y: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 1338
FT /note="G->D: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 1552..1556
FT /note="KKANK->LLANI: Fails to derepress of GCN4 translation
FT and amino acid biosynthetic genes in amino acid-starved
FT cells and does not inhibit autophosphorylation."
FT /evidence="ECO:0000269|PubMed:9430731"
FT MUTAGEN 1552
FT /note="K->L: Reduces interaction with TIF11, Inhibits
FT binding to uncharged tRNAs, reduces autophosphorylation,
FT eIF-2-alpha kinase activity and ribosome association, but
FT not dimerization; when associated with I-1553 and I-1556."
FT /evidence="ECO:0000269|PubMed:10983975,
FT ECO:0000269|PubMed:21849502"
FT MUTAGEN 1553
FT /note="K->I: Reduces interaction with TIF11, Inhibits
FT binding to uncharged tRNAs, reduces autophosphorylation,
FT eIF-2-alpha kinase activity and ribosome association, but
FT not dimerization; when associated with L-1552 and I-1556."
FT /evidence="ECO:0000269|PubMed:10983975,
FT ECO:0000269|PubMed:21849502"
FT MUTAGEN 1556
FT /note="K->I: Reduces interaction with TIF11, Inhibits
FT binding to uncharged tRNAs, reduces autophosphorylation,
FT eIF-2-alpha kinase activity and ribosome association, but
FT not dimerization; when associated with L-1552 and I-1553."
FT /evidence="ECO:0000269|PubMed:10983975,
FT ECO:0000269|PubMed:21849502"
FT MUTAGEN 1557
FT /note="R->K: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 1591
FT /note="E->K: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107"
FT MUTAGEN 1606
FT /note="E->K: Increases the constitutive kinase activity and
FT induces derepression of GCN4 translation and amino acid
FT biosynthetic genes in absence of amino acid starvation."
FT /evidence="ECO:0000269|PubMed:1448107,
FT ECO:0000269|PubMed:2188100"
FT CONFLICT 70
FT /note="M -> I (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 220..226
FT /note="TIKAKLP -> NYKGKIA (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 271..279
FT /note="LMSSEMMEN -> YVFSNHGKS (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 374
FT /note="M -> I (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 392
FT /note="K -> Q (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 395
FT /note="N -> S (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="F -> C (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 411..413
FT /note="IPK -> MPE (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="I -> M (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 589
FT /note="P -> A (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 604..605
FT /note="VL -> FS (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 622
FT /note="S -> T (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 640..641
FT /note="IL -> MI (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 727
FT /note="F -> C (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 839
FT /note="M -> K (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 954
FT /note="E -> Q (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 1144
FT /note="K -> E (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 1328..1331
FT /note="TLIS -> RFHT (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 1348
FT /note="V -> A (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 1356
FT /note="T -> I (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT CONFLICT 1434
FT /note="V -> I (in Ref. 4; AAA34881)"
FT /evidence="ECO:0000305"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:2YZ0"
FT HELIX 8..23
FT /evidence="ECO:0007829|PDB:2YZ0"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:2YZ0"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:2YZ0"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:2YZ0"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:2YZ0"
FT STRAND 80..84
FT /evidence="ECO:0007829|PDB:2YZ0"
FT HELIX 92..107
FT /evidence="ECO:0007829|PDB:2YZ0"
FT HELIX 114..130
FT /evidence="ECO:0007829|PDB:2YZ0"
FT HELIX 594..598
FT /evidence="ECO:0007829|PDB:1ZY4"
FT STRAND 599..607
FT /evidence="ECO:0007829|PDB:1ZY4"
FT STRAND 609..618
FT /evidence="ECO:0007829|PDB:1ZY4"
FT TURN 619..621
FT /evidence="ECO:0007829|PDB:1ZY4"
FT STRAND 624..633
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 634..647
FT /evidence="ECO:0007829|PDB:1ZY4"
FT STRAND 653..655
FT /evidence="ECO:0007829|PDB:1ZYC"
FT STRAND 658..664
FT /evidence="ECO:0007829|PDB:1ZY4"
FT STRAND 781..789
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 796..802
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 805..807
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 809..828
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 838..840
FT /evidence="ECO:0007829|PDB:1ZY4"
FT STRAND 841..843
FT /evidence="ECO:0007829|PDB:1ZY4"
FT STRAND 849..851
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 888..890
FT /evidence="ECO:0007829|PDB:1ZXE"
FT HELIX 893..896
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 905..919
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 925..936
FT /evidence="ECO:0007829|PDB:1ZY4"
FT TURN 948..950
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 952..961
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 966..968
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 972..977
FT /evidence="ECO:0007829|PDB:1ZY4"
FT HELIX 986..995
FT /evidence="ECO:0007829|PDB:1ZY4"
FT STRAND 1541..1543
FT /evidence="ECO:0007829|PDB:4OTM"
FT STRAND 1551..1553
FT /evidence="ECO:0007829|PDB:4OTM"
FT HELIX 1560..1577
FT /evidence="ECO:0007829|PDB:4OTM"
FT STRAND 1582..1586
FT /evidence="ECO:0007829|PDB:4OTM"
FT HELIX 1590..1598
FT /evidence="ECO:0007829|PDB:4OTM"
FT STRAND 1601..1603
FT /evidence="ECO:0007829|PDB:4OTM"
FT HELIX 1604..1612
FT /evidence="ECO:0007829|PDB:4OTM"
FT HELIX 1615..1617
FT /evidence="ECO:0007829|PDB:4OTM"
FT HELIX 1621..1636
FT /evidence="ECO:0007829|PDB:4OTM"
FT STRAND 1641..1646
FT /evidence="ECO:0007829|PDB:4OTM"
FT TURN 1647..1649
FT /evidence="ECO:0007829|PDB:4OTM"
FT STRAND 1652..1656
FT /evidence="ECO:0007829|PDB:4OTM"
SQ SEQUENCE 1659 AA; 190193 MW; 1F56E4B046D52325 CRC64;
MSLSHLTLDQ YYEIQCNELE AIRSIYMDDF TDLTKRKSSW DKQPQIIFEI TLRSVDKEPV
ESSITLHFAM TPMYPYTAPE IEFKNVQNVM DSQLQMLKSE FKKIHNTSRG QEIIFEITSF
TQEKLDEFQN VVNTQSLEDD RLQRIKETKE QLEKEEREKQ QETIKKRSDE QRRIDEIVQR
ELEKRQDDDD DLLFNRTTQL DLQPPSEWVA SGEAIVFSKT IKAKLPNNSM FKFKAVVNPK
PIKLTSDIFS FSKQFLVKPY IPPESPLADF LMSSEMMENF YYLLSEIELD NSYFNTSNGK
KEIANLEKEL ETVLKAKHDN VNRLFGYTVE RMGRNNATFV WKIRLLTEYC NYYPLGDLIQ
SVGFVNLATA RIWMIRLLEG LEAIHKLGIV HKCINLETVI LVKDADFGST IPKLVHSTYG
YTVLNMLSRY PNKNGSSVEL SPSTWIAPEL LKFNNAKPQR LTDIWQLGVL FIQIISGSDI
VMNFETPQEF LDSTSMDETL YDLLSKMLNN DPKKRLGTLE LLPMKFLRTN IDSTINRFNL
VSESVNSNSL ELTPGDTITV RGNGGRTLSQ SSIRRRSFNV GSRFSSINPA TRSRYASDFE
EIAVLGQGAF GQVVKARNAL DSRYYAIKKI RHTEEKLSTI LSEVMLLASL NHQYVVRYYA
AWLEEDSMDE NVFESTDEES DLSESSSDFE ENDLLDQSSI FKNRTNHDLD NSNWDFISGS
GYPDIVFENS SRDDENEDLD HDTSSTSSSE SQDDTDKESK SIQNVPRRRN FVKPMTAVKK
KSTLFIQMEY CENRTLYDLI HSENLNQQRD EYWRLFRQIL EALSYIHSQG IIHRDLKPMN
IFIDESRNVK IGDFGLAKNV HRSLDILKLD SQNLPGSSDN LTSAIGTAMY VATEVLDGTG
HYNEKIDMYS LGIIFFEMIY PFSTGMERVN ILKKLRSVSI EFPPDFDDNK MKVEKKIIRL
LIDHDPNKRP GARTLLNSGW LPVKHQDEVI KEALKSLSNP SSPWQQQVRE SLFNQSYSLT
NDILFDNSVP TSTPFANILR SQMTEEVVKI FRKHGGIENN APPRIFPKAP IYGTQNVYEV
LDKGGTVLQL QYDLTYPMAR YLSKNPSLIS KQYRMQHVYR PPDHSRSSLE PRKFGEIDFD
IISKSSSESG FYDAESLKII DEILTVFPVF EKTNTFFILN HADILESVFN FTNIDKAQRP
LVSRMLSQVG FARSFKEVKN ELKAQLNISS TALNDLELFD FRLDFEAAKK RLYKLMIDSP
HLKKIEDSLS HISKVLSYLK PLEVARNVVI SPLSNYNSAF YKGGIMFHAV YDDGSSRNMI
AAGGRYDTLI SFFARPSGKK SSNTRKAVGF NLAWETIFGI AQNYFKLASG NRIKKRNRFL
KDTAVDWKPS RCDVLISSFS NSLLDTIGVT ILNTLWKQNI KADMLRDCSS VDDVVTGAQQ
DGIDWILLIK QQAYPLTNHK RKYKPLKIKK LSTNVDIDLD LDEFLTLYQQ ETGNKSLIND
SLTLGDKADE FKRWDENSSA GSSQEGDIDD VVAGSTNNQK VIYVPNMATR SKKANKREKW
VYEDAARNSS NMILHNLSNA PIITVDALRD ETLEIISITS LAQKEEWLRK VFGSGNNSTP
RSFATSIYNN LSKEAHKGNR WAILYCHKTG KSSVIDLQR
