IF2A_YEAST
ID IF2A_YEAST Reviewed; 304 AA.
AC P20459; D6VWI2; E9P8T6;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Eukaryotic translation initiation factor 2 subunit alpha;
DE Short=eIF-2-alpha;
GN Name=SUI2 {ECO:0000303|PubMed:2649894, ECO:0000312|SGD:S000003767};
GN Synonyms=TIF211; OrderedLocusNames=YJR007W; ORFNames=J1429;
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=2649894; DOI=10.1073/pnas.86.8.2784;
RA Cigan A.M., Pabich E.K., Feng L., Donahue T.F.;
RT "Yeast translation initiation suppressor sui2 encodes the alpha subunit of
RT eukaryotic initiation factor 2 and shares sequence identity with the human
RT alpha subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:2784-2788(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL EMBO J. 15:2031-2049(1996).
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].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP FUNCTION, PHOSPHORYLATION AT SER-52 BY GCN2, AND MUTAGENESIS OF SER-52.
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 [6]
RP PHOSPHORYLATION AT SER-52 BY GCN2.
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 [7]
RP PHOSPHORYLATION AT SER-52 DURING CARBON STARVATION, AND MUTAGENESIS OF
RP SER-52.
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 [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292 AND SER-294, AND
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 [10]
RP X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 2-176.
RX PubMed=14607111; DOI=10.1016/j.jmb.2003.09.045;
RA Dhaliwal S., Hoffman D.W.;
RT "The crystal structure of the N-terminal region of the alpha subunit of
RT translation initiation factor 2 (eIF2alpha) from Saccharomyces cerevisiae
RT provides a view of the loop containing serine 51, the target of the
RT eIF2alpha-specific kinases.";
RL J. Mol. Biol. 334:187-195(2003).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 4-176.
RX PubMed=16179258; DOI=10.1016/j.cell.2005.06.044;
RA Dar A.C., Dever T.E., Sicheri F.;
RT "Higher-order substrate recognition of eIF2alpha by the RNA-dependent
RT protein kinase PKR.";
RL Cell 122:887-900(2005).
CC -!- FUNCTION: eIF-2 functions in the early steps of protein synthesis by
CC forming a ternary complex with GTP and initiator tRNA. This complex
CC binds to a 40S ribosomal subunit, followed by mRNA binding to form a
CC 43S pre-initiation complex. Junction of the 60S ribosomal subunit to
CC form the 80S initiation complex is preceded by hydrolysis of the GTP
CC bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for
CC eIF-2 to recycle and catalyze another round of initiation, the GDP
CC bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by
CC eIF-2B. {ECO:0000305}.
CC -!- SUBUNIT: Eukaryotic translation initiation factor 2 (eIF-2) is a
CC heterotrimer composed of an alpha, a beta and a gamma subunit. The
CC factors eIF-1, eIF-2, eIF-3, TIF5/eIF-5 and methionyl-tRNAi form a
CC multifactor complex (MFC) that may bind to the 40S ribosome.
CC {ECO:0000305}.
CC -!- INTERACTION:
CC P20459; P32481: GCD11; NbExp=11; IntAct=EBI-8915, EBI-8924;
CC P20459; P38431: TIF5; NbExp=4; IntAct=EBI-8915, EBI-9038;
CC -!- PTM: Phosphorylated; phosphorylation on Ser-52 by the GCN2 protein
CC kinase occurs in response to low amino acid, carbon, or purine
CC availability. {ECO:0000269|PubMed:10733573, ECO:0000269|PubMed:1739968,
CC ECO:0000269|PubMed:8336737}.
CC -!- MISCELLANEOUS: Present with 17100 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the eIF-2-alpha family. {ECO:0000305}.
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DR EMBL; M25552; AAA70332.1; -; Genomic_DNA.
DR EMBL; X87611; CAA60929.1; -; Genomic_DNA.
DR EMBL; Z49507; CAA89529.1; -; Genomic_DNA.
DR EMBL; AY557876; AAS56202.1; -; Genomic_DNA.
DR EMBL; BK006943; DAA08798.1; -; Genomic_DNA.
DR PIR; A32108; A32108.
DR RefSeq; NP_012540.3; NM_001181664.3.
DR PDB; 1Q46; X-ray; 2.86 A; A=2-176.
DR PDB; 2A19; X-ray; 2.50 A; A=4-176.
DR PDB; 2A1A; X-ray; 2.80 A; A=4-176.
DR PDB; 3J81; EM; 4.00 A; j=1-300.
DR PDB; 3JAP; EM; 4.90 A; j=1-304.
DR PDB; 3JAQ; EM; 6.00 A; j=1-304.
DR PDB; 6FYX; EM; 3.05 A; j=1-304.
DR PDB; 6FYY; EM; 3.05 A; j=1-304.
DR PDB; 6GSM; EM; 5.15 A; j=3-265.
DR PDB; 6GSN; EM; 5.75 A; j=3-265.
DR PDB; 6I3M; EM; 3.93 A; K/L=1-304.
DR PDB; 6I7T; EM; 4.61 A; K/L=1-304.
DR PDB; 6JLY; X-ray; 3.50 A; L/M=1-304.
DR PDB; 6JLZ; X-ray; 3.35 A; L/M=1-304.
DR PDB; 6QG0; EM; 4.20 A; K/L=1-304.
DR PDB; 6QG1; EM; 4.20 A; K/L=1-304.
DR PDB; 6QG2; EM; 4.60 A; K/L=1-304.
DR PDB; 6QG3; EM; 9.40 A; K/L=1-304.
DR PDB; 6QG5; EM; 10.10 A; K/L=1-304.
DR PDB; 6QG6; EM; 4.65 A; K/L=1-304.
DR PDBsum; 1Q46; -.
DR PDBsum; 2A19; -.
DR PDBsum; 2A1A; -.
DR PDBsum; 3J81; -.
DR PDBsum; 3JAP; -.
DR PDBsum; 3JAQ; -.
DR PDBsum; 6FYX; -.
DR PDBsum; 6FYY; -.
DR PDBsum; 6GSM; -.
DR PDBsum; 6GSN; -.
DR PDBsum; 6I3M; -.
DR PDBsum; 6I7T; -.
DR PDBsum; 6JLY; -.
DR PDBsum; 6JLZ; -.
DR PDBsum; 6QG0; -.
DR PDBsum; 6QG1; -.
DR PDBsum; 6QG2; -.
DR PDBsum; 6QG3; -.
DR PDBsum; 6QG5; -.
DR PDBsum; 6QG6; -.
DR AlphaFoldDB; P20459; -.
DR SMR; P20459; -.
DR BioGRID; 33763; 322.
DR ComplexPortal; CPX-427; Eukaryotic translation initiation factor 2 complex.
DR DIP; DIP-2327N; -.
DR IntAct; P20459; 35.
DR MINT; P20459; -.
DR STRING; 4932.YJR007W; -.
DR iPTMnet; P20459; -.
DR MaxQB; P20459; -.
DR PaxDb; P20459; -.
DR PRIDE; P20459; -.
DR EnsemblFungi; YJR007W_mRNA; YJR007W; YJR007W.
DR GeneID; 853463; -.
DR KEGG; sce:YJR007W; -.
DR SGD; S000003767; SUI2.
DR VEuPathDB; FungiDB:YJR007W; -.
DR eggNOG; KOG2916; Eukaryota.
DR GeneTree; ENSGT00390000007015; -.
DR HOGENOM; CLU_033458_0_1_1; -.
DR InParanoid; P20459; -.
DR OMA; DVNEHQR; -.
DR BioCyc; YEAST:G3O-31653-MON; -.
DR Reactome; R-SCE-156827; L13a-mediated translational silencing of Ceruloplasmin expression.
DR Reactome; R-SCE-381042; PERK regulates gene expression.
DR Reactome; R-SCE-72695; Formation of the ternary complex, and subsequently, the 43S complex.
DR Reactome; R-SCE-72702; Ribosomal scanning and start codon recognition.
DR Reactome; R-SCE-72731; Recycling of eIF2:GDP.
DR EvolutionaryTrace; P20459; -.
DR PRO; PR:P20459; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P20459; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0010494; C:cytoplasmic stress granule; HDA:SGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0033290; C:eukaryotic 48S preinitiation complex; IDA:SGD.
DR GO; GO:0005850; C:eukaryotic translation initiation factor 2 complex; IMP:SGD.
DR GO; GO:0005851; C:eukaryotic translation initiation factor 2B complex; IBA:GO_Central.
DR GO; GO:0043614; C:multi-eIF complex; IDA:SGD.
DR GO; GO:0005840; C:ribosome; IDA:ComplexPortal.
DR GO; GO:0043022; F:ribosome binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003743; F:translation initiation factor activity; IBA:GO_Central.
DR GO; GO:0001731; P:formation of translation preinitiation complex; IDA:SGD.
DR GO; GO:0006413; P:translational initiation; IDA:ComplexPortal.
DR CDD; cd04452; S1_IF2_alpha; 1.
DR Gene3D; 1.10.150.190; -; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.30.70.1130; -; 1.
DR IDEAL; IID50184; -.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR022967; S1_dom.
DR InterPro; IPR003029; S1_domain.
DR InterPro; IPR044126; S1_IF2_alpha.
DR InterPro; IPR024055; TIF2_asu_C.
DR InterPro; IPR024054; TIF2_asu_middle_sf.
DR InterPro; IPR011488; TIF_2_asu.
DR PANTHER; PTHR10602; PTHR10602; 1.
DR Pfam; PF07541; EIF_2_alpha; 1.
DR Pfam; PF00575; S1; 1.
DR SMART; SM00316; S1; 1.
DR SUPFAM; SSF110993; SSF110993; 1.
DR SUPFAM; SSF116742; SSF116742; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR PROSITE; PS50126; S1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Initiation factor; Phosphoprotein; Protein biosynthesis;
KW Reference proteome; RNA-binding.
FT CHAIN 1..304
FT /note="Eukaryotic translation initiation factor 2 subunit
FT alpha"
FT /id="PRO_0000137389"
FT DOMAIN 17..88
FT /note="S1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00180"
FT REGION 283..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 52
FT /note="Phosphoserine; by GCN2"
FT /evidence="ECO:0000269|PubMed:10733573,
FT ECO:0000269|PubMed:1739968, ECO:0000269|PubMed:8336737"
FT MOD_RES 292
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MUTAGEN 52
FT /note="S->A: Inhibits derepression of GCN4 expression in
FT amino acid, purine, and glucose-starved cells."
FT /evidence="ECO:0000269|PubMed:10733573,
FT ECO:0000269|PubMed:1739968"
FT MUTAGEN 52
FT /note="S->D: Weakly impairs derepression of GCN4 expression
FT in amino acid-starved cells."
FT /evidence="ECO:0000269|PubMed:1739968"
FT CONFLICT 258
FT /note="Y -> H (in Ref. 4; AAS56202)"
FT /evidence="ECO:0000305"
FT STRAND 8..13
FT /evidence="ECO:0007829|PDB:2A19"
FT STRAND 19..28
FT /evidence="ECO:0007829|PDB:2A19"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:2A19"
FT TURN 37..41
FT /evidence="ECO:0007829|PDB:2A19"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:2A19"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:1Q46"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:6JLZ"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:1Q46"
FT STRAND 67..77
FT /evidence="ECO:0007829|PDB:2A19"
FT TURN 78..81
FT /evidence="ECO:0007829|PDB:2A19"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:2A19"
FT HELIX 92..118
FT /evidence="ECO:0007829|PDB:2A19"
FT HELIX 123..129
FT /evidence="ECO:0007829|PDB:2A19"
FT HELIX 131..138
FT /evidence="ECO:0007829|PDB:2A19"
FT HELIX 141..150
FT /evidence="ECO:0007829|PDB:2A19"
FT HELIX 152..155
FT /evidence="ECO:0007829|PDB:2A19"
FT HELIX 163..173
FT /evidence="ECO:0007829|PDB:2A19"
SQ SEQUENCE 304 AA; 34718 MW; AF4F1C80303A4E98 CRC64;
MSTSHCRFYE NKYPEIDDIV MVNVQQIAEM GAYVKLLEYD NIEGMILLSE LSRRRIRSIQ
KLIRVGKNDV AVVLRVDKEK GYIDLSKRRV SSEDIIKCEE KYQKSKTVHS ILRYCAEKFQ
IPLEELYKTI AWPLSRKFGH AYEAFKLSII DETVWEGIEP PSKDVLDELK NYISKRLTPQ
AVKIRADVEV SCFSYEGIDA IKDALKSAED MSTEQMQVKV KLVAAPLYVL TTQALDKQKG
IEQLESAIEK ITEVITKYGG VCNITMPPKA VTATEDAELQ ALLESKELDN RSDSEDDEDE
SDDE
