EI2BE_YEAST
ID EI2BE_YEAST Reviewed; 712 AA.
AC P32501; D6VSJ5;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Translation initiation factor eIF-2B subunit epsilon;
DE AltName: Full=GCD complex subunit GCD6;
DE AltName: Full=Guanine nucleotide exchange factor subunit GCD6;
DE AltName: Full=eIF-2B GDP-GTP exchange factor subunit epsilon;
GN Name=GCD6; Synonyms=TIF225; OrderedLocusNames=YDR211W;
GN ORFNames=YD8142.12, YD8142B.03;
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=8441423; DOI=10.1128/mcb.13.3.1920-1932.1993;
RA Bushman J.L., Asuru A.I., Matts R.L., Hinnebusch A.G.;
RT "Evidence that GCD6 and GCD7, translational regulators of GCN4, are
RT subunits of the guanine nucleotide exchange factor for eIF-2 in
RT Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 13:1920-1932(1993).
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 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 INTERACTION WITH SUI3, AND MUTAGENESIS OF 655-THR--TRP-677 AND
RP 696-TRP--GLU-706.
RX PubMed=10075937; DOI=10.1093/emboj/18.6.1673;
RA Asano K., Krishnamoorthy T., Phan L., Pavitt G.D., Hinnebusch A.G.;
RT "Conserved bipartite motifs in yeast eIF5 and eIF2Bepsilon, GTPase-
RT activating and GDP-GTP exchange factors in translation initiation, mediate
RT binding to their common substrate eIF2.";
RL EMBO J. 18:1673-1688(1999).
RN [7]
RP MUTAGENESIS OF THR-552 AND SER-576.
RX PubMed=10805739; DOI=10.1128/mcb.20.11.3965-3976.2000;
RA Gomez E., Pavitt G.D.;
RT "Identification of domains and residues within the epsilon subunit of
RT eukaryotic translation initiation factor 2B (eIF2Bepsilon) required for
RT guanine nucleotide exchange reveals a novel activation function promoted by
RT eIF2B complex formation.";
RL Mol. Cell. Biol. 20:3965-3976(2000).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14690591; DOI=10.1016/s1097-2765(03)00476-3;
RA Hazbun T.R., Malmstroem L., Anderson S., Graczyk B.J., Fox B., Riffle M.,
RA Sundin B.A., Aranda J.D., McDonald W.H., Chiu C.-H., Snydsman B.E.,
RA Bradley P., Muller E.G.D., Fields S., Baker D., Yates J.R. III, Davis T.N.;
RT "Assigning function to yeast proteins by integration of technologies.";
RL Mol. Cell 12:1353-1365(2003).
RN [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-478; SER-481 AND SER-507, AND
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-538, 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-478; SER-481; SER-525;
RP SER-538 AND SER-707, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 524-712, AND MUTAGENESIS OF
RP GLU-569.
RX PubMed=14681227; DOI=10.1074/jbc.m311055200;
RA Boesen T., Mohammad S.S., Pavitt G.D., Andersen G.R.;
RT "Structure of the catalytic fragment of translation initiation factor 2B
RT and identification of a critically important catalytic residue.";
RL J. Biol. Chem. 279:10584-10592(2004).
CC -!- FUNCTION: Acts as a catalytic component of the translation initiation
CC factor 2B (eIF2-B or GCD complex), which catalyzes the exchange of
CC eukaryotic initiation factor 2 (eIF-2)-bound GDP for GTP and is
CC regulated by phosphorylated eIF-2. It activates the synthesis of GCN4
CC in yeast under amino acid starvation conditions by suppressing the
CC inhibitory effects of multiple AUG codons present in the leader of GCN4
CC mRNA. It may promote either repression or activation of GCN4 expression
CC depending on amino acid availability. GCD6 and GCD7 repress GCN4
CC expression at the translational level by ensuring that ribosomes which
CC have translated UORF1 will reinitiate at UORF2, -3, or -4 and thus fail
CC to reach the GCN4 start site. {ECO:0000269|PubMed:8506384,
CC ECO:0000269|PubMed:9472020}.
CC -!- SUBUNIT: Translation initiation factor 2B (eIF2-B) is composed of five
CC different subunits; alpha (GCN3), beta (GCD7), gamma (GCD1), delta
CC (GCD2) and epsilon (GCD6). A catalytic subcomplex comprising GCD1 and
CC GCD6 interacts with both, phosphorylated and non-phosphorylated eIF-2
CC and has exchange activity in vitro. GCD6 interacts with SUI3.
CC {ECO:0000269|PubMed:10075937, ECO:0000269|PubMed:8506384,
CC ECO:0000269|PubMed:9472020}.
CC -!- INTERACTION:
CC P32501; P09032: GCD1; NbExp=8; IntAct=EBI-6270, EBI-6275;
CC -!- MISCELLANEOUS: Present with 33800 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the eIF-2B gamma/epsilon subunits family.
CC {ECO:0000305}.
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DR EMBL; L07115; AAA65498.1; -; Genomic_DNA.
DR EMBL; Z68194; CAA92354.1; -; Genomic_DNA.
DR EMBL; Z68195; CAA92362.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA12055.1; -; Genomic_DNA.
DR PIR; A48156; A48156.
DR RefSeq; NP_010497.3; NM_001180519.3.
DR PDB; 1PAQ; X-ray; 2.30 A; A=524-712.
DR PDB; 6I3M; EM; 3.93 A; G/H=1-712.
DR PDB; 6I7T; EM; 4.61 A; G/H=1-712.
DR PDB; 6QG0; EM; 4.20 A; I/J=1-712.
DR PDB; 6QG1; EM; 4.20 A; I/J=1-712.
DR PDB; 6QG2; EM; 4.60 A; I/J=1-712.
DR PDB; 6QG3; EM; 9.40 A; I/J=1-712.
DR PDB; 6QG5; EM; 10.10 A; I/J=1-712.
DR PDB; 6QG6; EM; 4.65 A; I/J=1-712.
DR PDBsum; 1PAQ; -.
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; P32501; -.
DR SMR; P32501; -.
DR BioGRID; 32265; 120.
DR ComplexPortal; CPX-429; Eukaryotic translation initiation factor 2B complex.
DR DIP; DIP-2328N; -.
DR IntAct; P32501; 31.
DR MINT; P32501; -.
DR STRING; 4932.YDR211W; -.
DR iPTMnet; P32501; -.
DR MaxQB; P32501; -.
DR PaxDb; P32501; -.
DR PRIDE; P32501; -.
DR EnsemblFungi; YDR211W_mRNA; YDR211W; YDR211W.
DR GeneID; 851797; -.
DR KEGG; sce:YDR211W; -.
DR SGD; S000002619; GCD6.
DR VEuPathDB; FungiDB:YDR211W; -.
DR eggNOG; KOG1461; Eukaryota.
DR GeneTree; ENSGT00510000047568; -.
DR HOGENOM; CLU_012507_1_0_1; -.
DR InParanoid; P32501; -.
DR OMA; HYLYDKD; -.
DR BioCyc; YEAST:G3O-29793-MON; -.
DR BRENDA; 3.6.5.3; 984.
DR Reactome; R-SCE-72731; Recycling of eIF2:GDP.
DR EvolutionaryTrace; P32501; -.
DR PRO; PR:P32501; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P32501; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
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:0005085; F:guanyl-nucleotide exchange factor activity; IDA:SGD.
DR GO; GO:0016779; F:nucleotidyltransferase activity; IEA:InterPro.
DR GO; GO:0003743; F:translation initiation factor activity; IGI:SGD.
DR GO; GO:0031369; F:translation initiation factor binding; IBA:GO_Central.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:ComplexPortal.
DR GO; GO:0006446; P:regulation of translational initiation; IDA:SGD.
DR CDD; cd04197; eIF-2B_epsilon_N; 1.
DR CDD; cd11558; W2_eIF2B_epsilon; 1.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR035543; eIF-2B_epsilon_N.
DR InterPro; IPR001451; Hexapep.
DR InterPro; IPR005835; NTP_transferase_dom.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR InterPro; IPR011004; Trimer_LpxA-like_sf.
DR InterPro; IPR003307; W2_domain.
DR InterPro; IPR044123; W2_eIF2B_epsilon.
DR Pfam; PF00132; Hexapep; 2.
DR Pfam; PF00483; NTP_transferase; 1.
DR Pfam; PF02020; W2; 1.
DR SMART; SM00515; eIF5C; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF51161; SSF51161; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR PROSITE; PS51363; W2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Initiation factor; Phosphoprotein; Protein biosynthesis;
KW Reference proteome; Translation regulation.
FT CHAIN 1..712
FT /note="Translation initiation factor eIF-2B subunit
FT epsilon"
FT /id="PRO_0000156078"
FT DOMAIN 539..710
FT /note="W2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00695"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 481
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 707
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MUTAGEN 552
FT /note="T->I: Reduced exchange activity."
FT /evidence="ECO:0000269|PubMed:10805739"
FT MUTAGEN 569
FT /note="E->A: Lethal."
FT /evidence="ECO:0000269|PubMed:14681227"
FT MUTAGEN 576
FT /note="S->N: Reduced exchange activity."
FT /evidence="ECO:0000269|PubMed:10805739"
FT MUTAGEN 655..677
FT /note="LFSALVSLYDNDIIEEDVIYKWW->AFSAAVSAADNDAAEAAVAAKWA:
FT Abolishes binding to SUI3."
FT /evidence="ECO:0000269|PubMed:10075937"
FT MUTAGEN 696..706
FT /note="WVEWLQNADEE->AAEAAQNAAAA: Abolishes binding to SUI3;
FT probably impairs the conversion of eIF-2-GDP to eIF-2-GTP."
FT /evidence="ECO:0000269|PubMed:10075937"
FT HELIX 545..558
FT /evidence="ECO:0007829|PDB:1PAQ"
FT HELIX 563..576
FT /evidence="ECO:0007829|PDB:1PAQ"
FT HELIX 581..601
FT /evidence="ECO:0007829|PDB:1PAQ"
FT HELIX 607..618
FT /evidence="ECO:0007829|PDB:1PAQ"
FT HELIX 619..624
FT /evidence="ECO:0007829|PDB:1PAQ"
FT HELIX 629..646
FT /evidence="ECO:0007829|PDB:1PAQ"
FT HELIX 651..664
FT /evidence="ECO:0007829|PDB:1PAQ"
FT HELIX 670..678
FT /evidence="ECO:0007829|PDB:1PAQ"
FT HELIX 684..686
FT /evidence="ECO:0007829|PDB:1PAQ"
FT HELIX 687..702
FT /evidence="ECO:0007829|PDB:1PAQ"
SQ SEQUENCE 712 AA; 81161 MW; EFE87F6AE2941619 CRC64;
MAGKKGQKKS GLGNHGKNSD MDVEDRLQAV VLTDSYETRF MPLTAVKPRC LLPLANVPLI
EYTLEFLAKA GVHEVFLICS SHANQINDYI ENSKWNLPWS PFKITTIMSP EARCTGDVMR
DLDNRGIITG DFILVSGDVL TNIDFSKMLE FHKKMHLQDK DHISTMCLSK ASTYPKTRTI
EPAAFVLDKS TSRCIYYQDL PLPSSREKTS IQIDPELLDN VDEFVIRNDL IDCRIDICTS
HVPLIFQENF DYQSLRTDFV KGVISSDILG KHIYAYLTDE YAVRVESWQT YDTISQDFLG
RWCYPLVLDS NIQDDQTYSY ESRHIYKEKD VVLAQSCKIG KCTAIGSGTK IGEGTKIENS
VIGRNCQIGE NIRIKNSFIW DDCIIGNNSI IDHSLIASNA TLGSNVRLND GCIIGFNVKI
DDNMDLDRNT KISASPLKNA GSRMYDNESN EQFDQDLDDQ TLAVSIVGDK GVGYIYESEV
SDDEDSSTEA CKEINTLSNQ LDELYLSDDS ISSATKKTKK RRTMSVNSIY TDREEIDSEF
EDEDFEKEGI ATVERAMENN HDLDTALLEL NTLRMSMNVT YHEVRIATIT ALLRRVYHFI
ATQTLGPKDA VVKVFNQWGL LFKRQAFDEE EYIDLMNIIM EKIVEQSFDK PDLILFSALV
SLYDNDIIEE DVIYKWWDNV STDPRYDEVK KLTVKWVEWL QNADEESSSE EE
