ID   EI2BA_YEAST             Reviewed;         305 AA.
AC   P14741; D6VX91;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1990, sequence version 1.
DT   27-MAR-2024, entry version 193.
DE   RecName: Full=Translation initiation factor eIF2B subunit alpha;
DE   AltName: Full=GCD complex subunit GCN3;
DE   AltName: Full=Guanine nucleotide exchange factor subunit GCN3 {ECO:0000303|PubMed:8506384};
DE   AltName: Full=Translational activator GCN3 {ECO:0000303|PubMed:3062370};
DE   AltName: Full=eIF2B GDP-GTP exchange factor subunit alpha;
GN   Name=GCN3 {ECO:0000312|SGD:S000001734};
GN   Synonyms=AAS2 {ECO:0000312|SGD:S000001734}, TIF221;
GN   OrderedLocusNames=YKR026C;
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].
RX   PubMed=3062370; DOI=10.1128/mcb.8.11.4808-4820.1988;
RA   Hannig E.M., Hinnebusch A.G.;
RT   "Molecular analysis of GCN3, a translational activator of GCN4: evidence
RT   for posttranslational control of GCN3 regulatory function.";
RL   Mol. Cell. Biol. 8:4808-4820(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8196765; DOI=10.1038/369371a0;
RA   Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA   Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA   Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA   Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA   Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA   Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA   Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA   Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA   Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA   Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA   Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA   Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA   Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA   Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA   Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA   Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA   Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA   Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA   Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA   van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA   von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA   Becker I., Mewes H.-W.;
RT   "Complete DNA sequence of yeast chromosome XI.";
RL   Nature 369:371-378(1994).
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   IDENTIFICATION IN THE EIF2-B COMPLEX, AND FUNCTION OF THE EIF2-B COMPLEX.
RX   PubMed=8506384; DOI=10.1073/pnas.90.11.5350;
RA   Cigan A.M., Bushman J.L., Boal T.R., Hinnebusch A.G.;
RT   "A protein complex of translational regulators of GCN4 mRNA is the guanine
RT   nucleotide-exchange factor for translation initiation factor 2 in yeast.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:5350-5354(1993).
RN   [5]
RP   FUNCTION, AND IDENTIFICATION IN A EIF2-B SUBCOMPLEX.
RX   PubMed=9472020; DOI=10.1101/gad.12.4.514;
RA   Pavitt G.D., Ramaiah K.V., Kimball S.R., Hinnebusch A.G.;
RT   "eIF2 independently binds two distinct eIF2B subcomplexes that catalyze and
RT   regulate guanine-nucleotide exchange.";
RL   Genes Dev. 12:514-526(1998).
RN   [6]
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   [7]
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   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-291, AND IDENTIFICATION BY
RP   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   [9]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC   -!- FUNCTION: Acts as a component of the translation initiation factor 2B
CC       (eIF2B) complex, which catalyzes the exchange of GDP for GTP on the
CC       eukaryotic initiation factor 2 (eIF2) complex gamma subunit
CC       (PubMed:8506384, PubMed:9472020). Its guanine nucleotide exchange
CC       factor activity is repressed when bound to eIF2 complex phosphorylated
CC       on the alpha subunit, thereby limiting the amount of methionyl-
CC       initiator methionine tRNA available to the ribosome and consequently
CC       global translation is repressed (By similarity). It activates the
CC       translation of GCN4 in response to low amino acid, carbon, or purine
CC       availability, by suppressing the inhibitory effects of multiple uORFs
CC       present in the leader of GCN4 mRNA (PubMed:10733573). It may promote
CC       either repression or activation of GCN4 expression depending on amino
CC       acid availability (PubMed:8506384). Modulation of GCN3 regulatory
CC       function in response to amino acid availability occurs post-
CC       translationally (PubMed:8506384, PubMed:9472020).
CC       {ECO:0000250|UniProtKB:Q9USP0, ECO:0000269|PubMed:10733573,
CC       ECO:0000269|PubMed:8506384, ECO:0000269|PubMed:9472020}.
CC   -!- SUBUNIT: Component of the translation initiation factor 2B (eIF2B)
CC       complex which is a heterodecamer of two sets of five different
CC       subunits: alpha, beta, gamma, delta and epsilon. Subunits alpha, beta
CC       and delta comprise a regulatory subcomplex and subunits epsilon and
CC       gamma comprise a catalytic subcomplex (PubMed:8506384, PubMed:9472020).
CC       Within the complex, the hexameric regulatory complex resides at the
CC       center, with the two heterodimeric catalytic subcomplexes bound on
CC       opposite sides (By similarity). {ECO:0000250|UniProtKB:Q9USP0,
CC       ECO:0000269|PubMed:8506384, ECO:0000269|PubMed:9472020}.
CC   -!- INTERACTION:
CC       P14741; P12754: GCD2; NbExp=7; IntAct=EBI-6253, EBI-6265;
CC       P14741; P32502: GCD7; NbExp=10; IntAct=EBI-6253, EBI-6260;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:Q9USP0}.
CC   -!- DISRUPTION PHENOTYPE: Inhibits GCN4 derepression in glucose, amino
CC       acid, or purine-starved cells. {ECO:0000269|PubMed:10733573}.
CC   -!- MISCELLANEOUS: Present with 8970 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the eIF-2B alpha/beta/delta subunits family.
CC       {ECO:0000305}.
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DR   EMBL; M23356; AAA34637.1; -; Genomic_DNA.
DR   EMBL; Z28251; CAA82098.1; -; Genomic_DNA.
DR   EMBL; BK006944; DAA09181.1; -; Genomic_DNA.
DR   PIR; A31562; A31562.
DR   RefSeq; NP_012951.1; NM_001179816.1.
DR   PDB; 6I3M; EM; 3.93 A; A/B=1-305.
DR   PDB; 6I7T; EM; 4.61 A; A/B=1-305.
DR   PDB; 6QG0; EM; 4.20 A; A/B=1-305.
DR   PDB; 6QG1; EM; 4.20 A; A/B=1-305.
DR   PDB; 6QG2; EM; 4.60 A; A/B=1-305.
DR   PDB; 6QG3; EM; 9.40 A; A/B=1-305.
DR   PDB; 6QG5; EM; 10.10 A; A/B=1-305.
DR   PDB; 6QG6; EM; 4.65 A; A/B=1-305.
DR   PDBsum; 6I3M; -.
DR   PDBsum; 6I7T; -.
DR   PDBsum; 6QG0; -.
DR   PDBsum; 6QG1; -.
DR   PDBsum; 6QG2; -.
DR   PDBsum; 6QG3; -.
DR   PDBsum; 6QG5; -.
DR   PDBsum; 6QG6; -.
DR   AlphaFoldDB; P14741; -.
DR   EMDB; EMD-4404; -.
DR   EMDB; EMD-4428; -.
DR   EMDB; EMD-4543; -.
DR   EMDB; EMD-4544; -.
DR   EMDB; EMD-4545; -.
DR   EMDB; EMD-4546; -.
DR   EMDB; EMD-4547; -.
DR   EMDB; EMD-4548; -.
DR   SMR; P14741; -.
DR   BioGRID; 34158; 186.
DR   ComplexPortal; CPX-429; Eukaryotic translation initiation factor 2B complex.
DR   DIP; DIP-1328N; -.
DR   IntAct; P14741; 82.
DR   MINT; P14741; -.
DR   STRING; 4932.YKR026C; -.
DR   iPTMnet; P14741; -.
DR   MaxQB; P14741; -.
DR   PaxDb; 4932-YKR026C; -.
DR   PeptideAtlas; P14741; -.
DR   EnsemblFungi; YKR026C_mRNA; YKR026C; YKR026C.
DR   GeneID; 853896; -.
DR   KEGG; sce:YKR026C; -.
DR   AGR; SGD:S000001734; -.
DR   SGD; S000001734; GCN3.
DR   VEuPathDB; FungiDB:YKR026C; -.
DR   eggNOG; KOG1466; Eukaryota.
DR   GeneTree; ENSGT00550000074853; -.
DR   HOGENOM; CLU_016218_0_2_1; -.
DR   InParanoid; P14741; -.
DR   OMA; GDWESCK; -.
DR   OrthoDB; 51607at2759; -.
DR   BioCyc; YEAST:G3O-32002-MONOMER; -.
DR   Reactome; R-SCE-72731; Recycling of eIF2:GDP.
DR   BioGRID-ORCS; 853896; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P14741; -.
DR   Proteomes; UP000002311; Chromosome XI.
DR   RNAct; P14741; Protein.
DR   GO; GO:0005829; C:cytosol; HDA:SGD.
DR   GO; GO:0005851; C:eukaryotic translation initiation factor 2B complex; IDA:SGD.
DR   GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; IDA:SGD.
DR   GO; GO:0030234; F:enzyme regulator activity; IMP:SGD.
DR   GO; GO:0003743; F:translation initiation factor activity; IDA:SGD.
DR   GO; GO:0002183; P:cytoplasmic translational initiation; ISS:UniProtKB.
DR   GO; GO:1903833; P:positive regulation of cellular response to amino acid starvation; IMP:SGD.
DR   GO; GO:0006446; P:regulation of translational initiation; IDA:SGD.
DR   GO; GO:0006413; P:translational initiation; IBA:GO_Central.
DR   Gene3D; 1.20.120.1070; Translation initiation factor eIF-2B, N-terminal domain; 1.
DR   InterPro; IPR042528; elF-2B_alpha_N.
DR   InterPro; IPR000649; IF-2B-related.
DR   InterPro; IPR042529; IF_2B-like_C.
DR   InterPro; IPR037171; NagB/RpiA_transferase-like.
DR   PANTHER; PTHR45860; TRANSLATION INITIATION FACTOR EIF-2B SUBUNIT ALPHA; 1.
DR   PANTHER; PTHR45860:SF1; TRANSLATION INITIATION FACTOR EIF-2B SUBUNIT ALPHA; 1.
DR   Pfam; PF01008; IF-2B; 1.
DR   SUPFAM; SSF100950; NagB/RpiA/CoA transferase-like; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Activator; Cytoplasm; Initiation factor;
KW   Phosphoprotein; Protein biosynthesis; Reference proteome; Repressor;
KW   Translation regulation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   CHAIN           2..305
FT                   /note="Translation initiation factor eIF2B subunit alpha"
FT                   /id="PRO_0000156060"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   MOD_RES         291
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
SQ   SEQUENCE   305 AA;  34025 MW;  8E9A928D6D56E12B CRC64;
     MSEFNITETY LRFLEEDTEM TMPIAAIEAL VTLLRIKTPE TAAEMINTIK SSTEELIKSI
     PNSVSLRAGC DIFMRFVLRN LHLYGDWENC KQHLIENGQL FVSRAKKSRN KIAEIGVDFI
     ADDDIILVHG YSRAVFSLLN HAANKFIRFR CVVTESRPSK QGNQLYTLLE QKGIPVTLIV
     DSAVGAVIDK VDKVFVGAEG VAESGGIINL VGTYSVGVLA HNARKPFYVV TESHKFVRMF
     PLSSDDLPMA GPPLDFTRRT DDLEDALRGP TIDYTAQEYI TALITDLGVL TPSAVSEELI
     KMWYD
//