IF2A_HUMAN
ID IF2A_HUMAN Reviewed; 315 AA.
AC P05198;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Eukaryotic translation initiation factor 2 subunit 1;
DE AltName: Full=Eukaryotic translation initiation factor 2 subunit alpha;
DE Short=eIF-2-alpha;
DE Short=eIF-2A;
DE Short=eIF-2alpha;
GN Name=EIF2S1 {ECO:0000312|HGNC:HGNC:3265}; Synonyms=EIF2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fibroblast;
RX PubMed=2948954; DOI=10.1016/s0021-9258(19)75772-x;
RA Ernst H., Duncan R.F., Hershey J.W.B.;
RT "Cloning and sequencing of complementary DNAs encoding the alpha-subunit of
RT translational initiation factor eIF-2. Characterization of the protein and
RT its messenger RNA.";
RL J. Biol. Chem. 262:1206-1212(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION STATE REGULATION BY VACCINIA VIRUS PROTEIN E3, AND ACTIVITY
RP REGULATION.
RX PubMed=15207627; DOI=10.1016/j.virol.2004.03.012;
RA Langland J.O., Jacobs B.L.;
RT "Inhibition of PKR by vaccinia virus: role of the N- and C-terminal domains
RT of E3L.";
RL Virology 324:419-429(2004).
RN [4]
RP FUNCTION.
RX PubMed=16289705; DOI=10.1016/j.pep.2005.09.021;
RA Mikami S., Masutani M., Sonenberg N., Yokoyama S., Imataka H.;
RT "An efficient mammalian cell-free translation system supplemented with
RT translation factors.";
RL Protein Expr. Purif. 46:348-357(2006).
RN [5]
RP INTERACTION WITH ABCF1, AND ASSOCIATION WITH RIBOSOMES.
RX PubMed=17894550; DOI=10.1042/bj20070811;
RA Paytubi S., Morrice N.A., Boudeau J., Proud C.G.;
RT "The N-terminal region of ABC50 interacts with eukaryotic initiation factor
RT eIF2 and is a target for regulatory phosphorylation by CK2.";
RL Biochem. J. 409:223-231(2008).
RN [6]
RP PHOSPHORYLATION STATE REGULATION BY ROTAVIRUS A, AND ACTIVITY REGULATION.
RX PubMed=18032499; DOI=10.1128/jvi.01779-07;
RA Montero H., Rojas M., Arias C.F., Lopez S.;
RT "Rotavirus infection induces the phosphorylation of eIF2alpha but prevents
RT the formation of stress granules.";
RL J. Virol. 82:1496-1504(2008).
RN [7]
RP INTERACTION WITH DDX3X.
RX PubMed=18596238; DOI=10.1091/mbc.e07-12-1264;
RA Lai M.C., Lee Y.H., Tarn W.Y.;
RT "The DEAD-box RNA helicase DDX3 associates with export messenger
RT ribonucleoproteins as well as tip-associated protein and participates in
RT translational control.";
RL Mol. Biol. Cell 19:3847-3858(2008).
RN [8]
RP PHOSPHORYLATION, ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=19131336; DOI=10.1074/jbc.m806735200;
RA Lee Y.Y., Cevallos R.C., Jan E.;
RT "An upstream open reading frame regulates translation of GADD34 during
RT cellular stresses that induce eIF2alpha phosphorylation.";
RL J. Biol. Chem. 284:6661-6673(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-141, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP SUBUNIT.
RX PubMed=23063529; DOI=10.1016/j.molcel.2012.09.005;
RA Borck G., Shin B.S., Stiller B., Mimouni-Bloch A., Thiele H., Kim J.R.,
RA Thakur M., Skinner C., Aschenbach L., Smirin-Yosef P., Har-Zahav A.,
RA Nuernberg G., Altmueller J., Frommolt P., Hofmann K., Konen O.,
RA Nuernberg P., Munnich A., Schwartz C.E., Gothelf D., Colleaux L.,
RA Dever T.E., Kubisch C., Basel-Vanagaite L.;
RT "eIF2gamma mutation that disrupts eIF2 complex integrity links intellectual
RT disability to impaired translation initiation.";
RL Mol. Cell 48:641-646(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158; THR-279 AND THR-281, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [16]
RP FUNCTION, AND INDUCTION BY ER STRESS.
RX PubMed=33384352; DOI=10.1126/science.abb6896;
RA You K., Wang L., Chou C.H., Liu K., Nakata T., Jaiswal A., Yao J.,
RA Lefkovith A., Omar A., Perrigoue J.G., Towne J.E., Regev A., Graham D.B.,
RA Xavier R.J.;
RT "QRICH1 dictates the outcome of ER stress through transcriptional control
RT of proteostasis.";
RL Science 371:0-0(2021).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-183.
RX PubMed=11859078; DOI=10.1074/jbc.m111804200;
RA Nonato M.C., Widom J., Clardy J.;
RT "Crystal structure of the N-terminal segment of human eukaryotic
RT translation initiation factor 2alpha.";
RL J. Biol. Chem. 277:17057-17061(2002).
RN [18]
RP STRUCTURE BY NMR OF 5-303.
RX PubMed=15341733; DOI=10.1016/j.str.2004.07.010;
RA Ito T., Marintchev A., Wagner G.;
RT "Solution structure of human initiation factor eIF2alpha reveals homology
RT to the elongation factor eEF1B.";
RL Structure 12:1693-1704(2004).
CC -!- FUNCTION: Functions in the early steps of protein synthesis by forming
CC a ternary complex with GTP and initiator tRNA (PubMed:16289705). This
CC complex binds to a 40S ribosomal subunit, followed by mRNA binding to
CC form a 43S pre-initiation complex (PubMed:16289705). Junction of the
CC 60S ribosomal subunit to form the 80S initiation complex is preceded by
CC hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary
CC complex (PubMed:16289705). In order for eIF-2 to recycle and catalyze
CC another round of initiation, the GDP bound to eIF-2 must exchange with
CC GTP by way of a reaction catalyzed by eIF-2B (PubMed:16289705).
CC EIF2S1/eIF-2-alpha is a key component of the integrated stress response
CC (ISR), required for adaptation to various stress: phosphorylation by
CC metabolic-stress sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR,
CC EIF2AK3/PERK and EIF2AK4/GCN2) in response to stress converts
CC EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to
CC an attenuation of cap-dependent translation, while concomitantly
CC initiating the preferential translation of ISR-specific mRNAs, such as
CC the transcriptional activators ATF4 and QRICH1, and hence allowing
CC ATF4- and QRICH1-mediated reprogramming (PubMed:19131336,
CC PubMed:33384352). {ECO:0000269|PubMed:16289705,
CC ECO:0000269|PubMed:19131336, ECO:0000269|PubMed:33384352}.
CC -!- ACTIVITY REGULATION: Activity is regulated by phosphorylation at Ser-49
CC and Ser-52, which stabilizes the eIF-2/GDP/eIF-2B complex and prevents
CC the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the
CC formation of the 43S pre-initiation complex (PIC) (PubMed:15207627,
CC PubMed:18032499). This results in the global attenuation of 5' cap-
CC dependent protein synthesis and concomitant translation of ISR-specific
CC mRNAs that contain a short upstream open reading frame (uORF) in their
CC 5' UTR, such as ATF4, ATF5, DDIT3/CHOP and PPP1R15A/GADD34
CC (PubMed:19131336). {ECO:0000269|PubMed:15207627,
CC ECO:0000269|PubMed:18032499, ECO:0000269|PubMed:19131336}.
CC -!- SUBUNIT: Heterotrimer composed of an alpha, a beta and a gamma chain
CC (PubMed:23063529). Component of an EIF2 complex at least composed of
CC CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5.
CC Interaction with METAP2 protects EIF2S1 from inhibitory phosphorylation
CC (By similarity). Interacts with ABCF1 isoform 2 (PubMed:17894550).
CC Associates with ribosomes (PubMed:17894550). Interacts with DDX3X in an
CC RNA-independent manner (PubMed:18596238).
CC {ECO:0000250|UniProtKB:P68101, ECO:0000250|UniProtKB:Q6ZWX6,
CC ECO:0000269|PubMed:17894550, ECO:0000269|PubMed:18596238,
CC ECO:0000269|PubMed:23063529}.
CC -!- INTERACTION:
CC P05198; P12814: ACTN1; NbExp=3; IntAct=EBI-1056162, EBI-351710;
CC P05198; O00571: DDX3X; NbExp=3; IntAct=EBI-1056162, EBI-353779;
CC P05198; P19525: EIF2AK2; NbExp=5; IntAct=EBI-1056162, EBI-640775;
CC P05198; P20042: EIF2S2; NbExp=7; IntAct=EBI-1056162, EBI-711977;
CC P05198; P41091: EIF2S3; NbExp=4; IntAct=EBI-1056162, EBI-1054228;
CC P05198; P62136: PPP1CA; NbExp=2; IntAct=EBI-1056162, EBI-357253;
CC P05198; Q9NVM4: PRMT7; NbExp=5; IntAct=EBI-1056162, EBI-3215577;
CC P05198; Q08AM6: VAC14; NbExp=3; IntAct=EBI-1056162, EBI-2107455;
CC P05198; Q9Z2B5: Eif2ak3; Xeno; NbExp=4; IntAct=EBI-1056162, EBI-1226344;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:Q6ZWX6}. Note=Colocalizes with NANOS3 in the
CC stress granules. {ECO:0000250|UniProtKB:Q6ZWX6}.
CC -!- INDUCTION: Up-regulated upon endoplasmic reticulum stress.
CC {ECO:0000269|PubMed:33384352}.
CC -!- PTM: Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-2/GDP/eIF-
CC 2B complex and prevents GDP/GTP exchange reaction, thus impairing the
CC recycling of eIF-2 between successive rounds of initiation and leading
CC to global inhibition of translation, while concomitantly initiating the
CC preferential translation of integrated stress response (ISR)-specific
CC mRNAs (PubMed:15207627, PubMed:18032499, PubMed:19131336). Substrate
CC for at least 4 kinases: EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and
CC EIF2AK4/GCN2 (By similarity). Phosphorylated; phosphorylation on Ser-52
CC by the EIF2AK4/GCN2 protein kinase occurs in response to amino acid
CC starvation and UV irradiation (By similarity).
CC {ECO:0000250|UniProtKB:Q6ZWX6, ECO:0000269|PubMed:15207627,
CC ECO:0000269|PubMed:18032499, ECO:0000269|PubMed:19131336}.
CC -!- PTM: (Microbial infection) Phosphorylation by vaccinia virus protein E3
CC and rotavirus A stabilizes the eIF-2/GDP/eIF-2B complex and prevents
CC GDP/GTP exchange reaction, thus impairing the recycling of eIF-2
CC between successive rounds of initiation and leading to global
CC inhibition of translation. {ECO:0000269|PubMed:15207627,
CC ECO:0000269|PubMed:18032499}.
CC -!- SIMILARITY: Belongs to the eIF-2-alpha family. {ECO:0000305}.
CC -!- CAUTION: This gene should not be confused with EIF2A, with which it
CC shares the alias EIF2A. Although both of these proteins function in
CC binding initiator tRNA to the 40S ribosomal subunit, the eIF2 complex
CC requires GTP, whereas the EIF2A protein does so in a codon-dependent
CC manner. {ECO:0000305}.
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DR EMBL; J02645; AAA52373.1; -; mRNA.
DR EMBL; BC002513; AAH02513.1; -; mRNA.
DR CCDS; CCDS9781.1; -.
DR RefSeq; NP_004085.1; NM_004094.4.
DR PDB; 1KL9; X-ray; 1.90 A; A=2-183.
DR PDB; 1Q8K; NMR; -; A=5-303.
DR PDB; 6K71; EM; 4.30 A; K=1-315.
DR PDB; 6K72; EM; 4.60 A; K/L=1-315.
DR PDB; 6O81; EM; 3.21 A; L/M=1-315.
DR PDB; 6O85; EM; 3.03 A; L=2-315.
DR PDB; 6O9Z; EM; 3.03 A; L/M=2-315.
DR PDB; 6YBV; EM; 3.80 A; r=1-315.
DR PDB; 6ZMW; EM; 3.70 A; r=1-315.
DR PDB; 6ZP4; EM; 2.90 A; O=1-315.
DR PDB; 7A09; EM; 3.50 A; O=1-315.
DR PDB; 7D43; EM; 4.30 A; K/L=1-315.
DR PDB; 7D44; EM; 4.00 A; K/L=1-315.
DR PDB; 7D45; EM; 3.80 A; K=1-315.
DR PDB; 7F66; EM; 2.76 A; N=1-315.
DR PDB; 7F67; EM; 3.59 A; N/Q=1-315.
DR PDB; 7NZM; EM; 3.96 A; E=2-187.
DR PDBsum; 1KL9; -.
DR PDBsum; 1Q8K; -.
DR PDBsum; 6K71; -.
DR PDBsum; 6K72; -.
DR PDBsum; 6O81; -.
DR PDBsum; 6O85; -.
DR PDBsum; 6O9Z; -.
DR PDBsum; 6YBV; -.
DR PDBsum; 6ZMW; -.
DR PDBsum; 6ZP4; -.
DR PDBsum; 7A09; -.
DR PDBsum; 7D43; -.
DR PDBsum; 7D44; -.
DR PDBsum; 7D45; -.
DR PDBsum; 7F66; -.
DR PDBsum; 7F67; -.
DR PDBsum; 7NZM; -.
DR AlphaFoldDB; P05198; -.
DR BMRB; P05198; -.
DR SMR; P05198; -.
DR BioGRID; 108285; 172.
DR CORUM; P05198; -.
DR DIP; DIP-39418N; -.
DR IntAct; P05198; 57.
DR MINT; P05198; -.
DR STRING; 9606.ENSP00000256383; -.
DR ChEMBL; CHEMBL1255131; -.
DR GlyGen; P05198; 5 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; P05198; -.
DR MetOSite; P05198; -.
DR PhosphoSitePlus; P05198; -.
DR SwissPalm; P05198; -.
DR BioMuta; EIF2S1; -.
DR DMDM; 124200; -.
DR OGP; P05198; -.
DR REPRODUCTION-2DPAGE; IPI00219678; -.
DR EPD; P05198; -.
DR jPOST; P05198; -.
DR MassIVE; P05198; -.
DR PaxDb; P05198; -.
DR PeptideAtlas; P05198; -.
DR PRIDE; P05198; -.
DR ProteomicsDB; 51824; -.
DR TopDownProteomics; P05198; -.
DR Antibodypedia; 3181; 924 antibodies from 39 providers.
DR DNASU; 1965; -.
DR Ensembl; ENST00000256383.11; ENSP00000256383.4; ENSG00000134001.15.
DR Ensembl; ENST00000466499.6; ENSP00000425299.1; ENSG00000134001.15.
DR GeneID; 1965; -.
DR KEGG; hsa:1965; -.
DR MANE-Select; ENST00000256383.11; ENSP00000256383.4; NM_004094.5; NP_004085.1.
DR CTD; 1965; -.
DR DisGeNET; 1965; -.
DR GeneCards; EIF2S1; -.
DR HGNC; HGNC:3265; EIF2S1.
DR HPA; ENSG00000134001; Low tissue specificity.
DR MIM; 603907; gene.
DR neXtProt; NX_P05198; -.
DR OpenTargets; ENSG00000134001; -.
DR PharmGKB; PA27695; -.
DR VEuPathDB; HostDB:ENSG00000134001; -.
DR eggNOG; KOG2916; Eukaryota.
DR GeneTree; ENSGT00390000007015; -.
DR InParanoid; P05198; -.
DR OMA; DVNEHQR; -.
DR OrthoDB; 1093186at2759; -.
DR PhylomeDB; P05198; -.
DR TreeFam; TF101502; -.
DR BRENDA; 3.6.5.3; 2681.
DR PathwayCommons; P05198; -.
DR Reactome; R-HSA-156827; L13a-mediated translational silencing of Ceruloplasmin expression.
DR Reactome; R-HSA-381042; PERK regulates gene expression.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR Reactome; R-HSA-72649; Translation initiation complex formation.
DR Reactome; R-HSA-72695; Formation of the ternary complex, and subsequently, the 43S complex.
DR Reactome; R-HSA-72702; Ribosomal scanning and start codon recognition.
DR Reactome; R-HSA-72706; GTP hydrolysis and joining of the 60S ribosomal subunit.
DR Reactome; R-HSA-72731; Recycling of eIF2:GDP.
DR Reactome; R-HSA-9633012; Response of EIF2AK4 (GCN2) to amino acid deficiency.
DR Reactome; R-HSA-9648895; Response of EIF2AK1 (HRI) to heme deficiency.
DR SignaLink; P05198; -.
DR SIGNOR; P05198; -.
DR BioGRID-ORCS; 1965; 794 hits in 1055 CRISPR screens.
DR EvolutionaryTrace; P05198; -.
DR GeneWiki; EIF2S1; -.
DR GenomeRNAi; 1965; -.
DR Pharos; P05198; Tbio.
DR PRO; PR:P05198; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P05198; protein.
DR Bgee; ENSG00000134001; Expressed in islet of Langerhans and 212 other tissues.
DR ExpressionAtlas; P05198; baseline and differential.
DR Genevisible; P05198; HS.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0033290; C:eukaryotic 48S preinitiation complex; IBA:GO_Central.
DR GO; GO:0005850; C:eukaryotic translation initiation factor 2 complex; IDA:UniProtKB.
DR GO; GO:0005851; C:eukaryotic translation initiation factor 2B complex; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0097451; C:glial limiting end-foot; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0043614; C:multi-eIF complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005844; C:polysome; TAS:ProtInc.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0044207; C:translation initiation ternary complex; IEA:Ensembl.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0003743; F:translation initiation factor activity; IDA:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:ARUK-UCL.
DR GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB.
DR GO; GO:1905098; P:negative regulation of guanyl-nucleotide exchange factor activity; IEA:Ensembl.
DR GO; GO:0032057; P:negative regulation of translational initiation in response to stress; ISS:UniProtKB.
DR GO; GO:0036499; P:PERK-mediated unfolded protein response; IDA:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; IMP:ParkinsonsUK-UCL.
DR GO; GO:2000676; P:positive regulation of type B pancreatic cell apoptotic process; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0043558; P:regulation of translational initiation in response to stress; IEA:Ensembl.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:1990737; P:response to manganese-induced endoplasmic reticulum stress; IEA:Ensembl.
DR GO; GO:0034063; P:stress granule assembly; ISS:ARUK-UCL.
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; IID00508; -.
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; Acetylation; Cytoplasm; Initiation factor; Phosphoprotein;
KW Protein biosynthesis; Reference proteome; RNA-binding;
KW Translation regulation.
FT CHAIN 1..315
FT /note="Eukaryotic translation initiation factor 2 subunit
FT 1"
FT /id="PRO_0000137382"
FT DOMAIN 17..88
FT /note="S1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00180"
FT REGION 293..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..315
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 49
FT /note="Phosphoserine; by HRI"
FT /evidence="ECO:0000250|UniProtKB:P83268"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 141
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 279
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 281
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT STRAND 8..13
FT /evidence="ECO:0007829|PDB:1KL9"
FT STRAND 19..27
FT /evidence="ECO:0007829|PDB:1KL9"
FT STRAND 29..36
FT /evidence="ECO:0007829|PDB:1KL9"
FT TURN 37..41
FT /evidence="ECO:0007829|PDB:1KL9"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:1KL9"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:1KL9"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:6O9Z"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:1Q8K"
FT STRAND 68..77
FT /evidence="ECO:0007829|PDB:1KL9"
FT TURN 78..81
FT /evidence="ECO:0007829|PDB:1KL9"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:1KL9"
FT HELIX 92..118
FT /evidence="ECO:0007829|PDB:1KL9"
FT HELIX 124..133
FT /evidence="ECO:0007829|PDB:1KL9"
FT HELIX 135..142
FT /evidence="ECO:0007829|PDB:1KL9"
FT HELIX 147..158
FT /evidence="ECO:0007829|PDB:1KL9"
FT HELIX 160..163
FT /evidence="ECO:0007829|PDB:1KL9"
FT HELIX 170..182
FT /evidence="ECO:0007829|PDB:1KL9"
FT STRAND 190..198
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:7F66"
FT HELIX 204..217
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:1Q8K"
FT STRAND 226..231
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 234..240
FT /evidence="ECO:0007829|PDB:7F66"
FT HELIX 244..264
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 268..277
FT /evidence="ECO:0007829|PDB:7F66"
FT HELIX 282..289
FT /evidence="ECO:0007829|PDB:1Q8K"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:1Q8K"
SQ SEQUENCE 315 AA; 36112 MW; FF3E75E3816E6B1E CRC64;
MPGLSCRFYQ HKFPEVEDVV MVNVRSIAEM GAYVSLLEYN NIEGMILLSE LSRRRIRSIN
KLIRIGRNEC VVVIRVDKEK GYIDLSKRRV SPEEAIKCED KFTKSKTVYS ILRHVAEVLE
YTKDEQLESL FQRTAWVFDD KYKRPGYGAY DAFKHAVSDP SILDSLDLNE DEREVLINNI
NRRLTPQAVK IRADIEVACY GYEGIDAVKE ALRAGLNCST ENMPIKINLI APPRYVMTTT
TLERTEGLSV LSQAMAVIKE KIEEKRGVFN VQMEPKVVTD TDETELARQM ERLERENAEV
DGDDDAEEME AKAED
