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 27-MAR-2024, entry version 230. 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; DE Short=eIF2-alpha; 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 INTERACTION WITH ROTAVIRUS A NON-STRUCTURAL PROTEIN 2 (MICROBIAL RP INFECTION), AND INTERACTION WITH ROTAVIRUS A NON-STRUCTURAL PROTEIN 5 RP (MICROBIAL INFECTION). RX PubMed=30258011; DOI=10.1128/jvi.01363-18; RA Dhillon P., Rao C.D.; RT "Rotavirus Induces Formation of Remodeled Stress Granules and P Bodies and RT Their Sequestration in Viroplasms To Promote Progeny Virus Production."; RL J. Virol. 92:0-0(2018). RN [17] RP IDENTIFICATION IN THE EIF2 COMPLEX, AND INTERACTION WITH CDC123. RX PubMed=31836389; DOI=10.1016/j.molcel.2019.11.008; RA Young-Baird S.K., Lourenco M.B., Elder M.K., Klann E., Liebau S., RA Dever T.E.; RT "Suppression of MEHMO Syndrome Mutation in eIF2 by Small Molecule ISRIB."; RL Mol. Cell 77:875-886(2020). RN [18] 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 [19] RP IDENTIFICATION IN THE EIF2 COMPLEX, AND INTERACTION WITH CDC123. RX PubMed=35031321; DOI=10.1016/j.jbc.2022.101583; RA Vanselow S., Neumann-Arnold L., Wojciech-Moock F., Seufert W.; RT "Stepwise assembly of the eukaryotic translation initiation factor 2 RT complex."; RL J. Biol. Chem. 298:101583-101583(2022). RN [20] 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 [21] 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). RN [22] {ECO:0007744|PDB:6K71, ECO:0007744|PDB:6K72} RP STRUCTURE BY ELECTRON MICROSCOPY (4.30 ANGSTROMS) IN COMPLEX WITH THE EIF2B RP COMPLEX, IDENTIFICATION IN THE EIF2 COMPLEX, AND PHOSPHORYLATION. RX PubMed=31048492; DOI=10.1126/science.aaw4104; RA Kashiwagi K., Yokoyama T., Nishimoto M., Takahashi M., Sakamoto A., RA Yonemochi M., Shirouzu M., Ito T.; RT "Structural basis for eIF2B inhibition in integrated stress response."; RL Science 364:495-499(2019). CC -!- FUNCTION: Member of the eIF2 complex that functions in the early steps CC of protein synthesis by forming a ternary complex with GTP and CC initiator tRNA (PubMed:16289705). This complex binds to a 40S ribosomal CC subunit, followed by mRNA binding to form a 43S pre-initiation complex CC (43S PIC) (PubMed:16289705). Junction of the 60S ribosomal subunit to CC form the 80S initiation complex is preceded by hydrolysis of the GTP CC bound to eIF2 and release of an eIF2-GDP binary complex CC (PubMed:16289705). In order for eIF2 to recycle and catalyze another CC round of initiation, the GDP bound to eIF2 must exchange with GTP by CC way of a reaction catalyzed by eIF2B (PubMed:16289705). EIF2S1/ CC component of the integrated stress response (ISR), required for CC adaptation to various stress: phosphorylation by metabolic-stress CC sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and CC EIF2AK4/GCN2) in response to stress converts EIF2S1/eIF2-alpha in a CC global protein synthesis inhibitor, leading to an attenuation of cap- CC dependent translation, while concomitantly initiating the preferential CC translation of ISR-specific mRNAs, such as the transcriptional CC activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1- CC mediated reprogramming (PubMed:19131336, PubMed:33384352). CC {ECO:0000269|PubMed:16289705, ECO:0000269|PubMed:19131336, CC ECO:0000269|PubMed:33384352}. CC -!- ACTIVITY REGULATION: Activity is regulated by phosphorylation at Ser-49 CC and Ser-52, which stabilizes the eIF2/GDP/eIF2B complex and prevents CC the eIF2B-mediated exchange of GDP for GTP, thereby preventing the CC formation of the 43S pre-initiation complex (43S 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: Eukaryotic translation initiation factor 2 eIF2 is a CC heterotrimeric complex composed of an alpha (EIF2S1), a beta (EIF2S2) CC and a gamma (EIF2S3) chain (PubMed:23063529, PubMed:31836389, CC PubMed:35031321, PubMed:31048492). eIF2 is member of the 43S pre- CC initiation complex (43S PIC). eIF2 forms a complex with at least CC CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (By CC similarity). Interaction with METAP2 protects EIF2S1 from inhibitory CC phosphorylation (By similarity). Interacts with ABCF1 isoform 2 CC (PubMed:17894550). Associates with ribosomes (PubMed:17894550). CC Interacts with DDX3X in an RNA-independent manner (PubMed:18596238). CC Interacts with CDC123 (PubMed:31836389, PubMed:35031321). CC {ECO:0000250|UniProtKB:P68101, ECO:0000250|UniProtKB:Q6ZWX6, CC ECO:0000269|PubMed:17894550, ECO:0000269|PubMed:18596238, CC ECO:0000269|PubMed:23063529, ECO:0000269|PubMed:31048492, CC ECO:0000269|PubMed:31836389, ECO:0000269|PubMed:35031321}. CC -!- SUBUNIT: (Microbial infection) Interacts with rotavirus A non- CC structural protein 2; this interaction probably plays a role in the CC sequestration of IF2A in viral factories (PubMed:30258011). Interacts CC with rotavirus A non-structural protein 5; this interaction probably CC plays a role in its sequestration in viral factories (PubMed:30258011). CC {ECO:0000269|PubMed:30258011}. 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=6; 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}. Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P56286}. 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- CC 2/GDP/eIF2B complex and prevents GDP/GTP exchange reaction, thus CC impairing the recycling of eIF2 between successive rounds of initiation CC and leading to global inhibition of translation, while concomitantly CC initiating the preferential translation of integrated stress response CC (ISR)-specific mRNAs (PubMed:15207627, PubMed:18032499, CC PubMed:19131336, PubMed:31048492). Substrate for at least 4 kinases: CC EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2 (By CC similarity). Phosphorylated; phosphorylation on Ser-52 by the CC EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation CC and UV irradiation (By similarity). {ECO:0000250|UniProtKB:Q6ZWX6, CC ECO:0000269|PubMed:15207627, ECO:0000269|PubMed:18032499, CC ECO:0000269|PubMed:19131336, ECO:0000269|PubMed:31048492}. CC -!- PTM: (Microbial infection) Phosphorylation by vaccinia virus protein E3 CC and rotavirus A stabilizes the eIF-2/GDP/eIF2B complex and prevents CC GDP/GTP exchange reaction, thus impairing the recycling of eIF2 between CC successive rounds of initiation and leading to global inhibition of CC 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}. 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; 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 PDB; 7QP6; EM; 4.70 A; r=1-315. DR PDB; 7QP7; EM; 3.70 A; r=1-315. DR PDB; 7SYR; EM; 3.60 A; j=1-315. DR PDB; 7SYS; EM; 3.50 A; j=1-315. DR PDB; 8PPL; EM; 2.65 A; Ir=1-315. 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 PDBsum; 7QP6; -. DR PDBsum; 7QP7; -. DR PDBsum; 7SYR; -. DR PDBsum; 7SYS; -. DR PDBsum; 8PPL; -. DR AlphaFoldDB; P05198; -. DR BMRB; P05198; -. DR EMDB; EMD-0649; -. DR EMDB; EMD-0651; -. DR EMDB; EMD-0664; -. DR EMDB; EMD-10774; -. DR EMDB; EMD-11302; -. DR EMDB; EMD-11335; -. DR EMDB; EMD-11602; -. DR EMDB; EMD-12665; -. DR EMDB; EMD-14113; -. DR EMDB; EMD-14114; -. DR EMDB; EMD-17805; -. DR EMDB; EMD-25538; -. DR EMDB; EMD-25539; -. DR EMDB; EMD-30568; -. DR EMDB; EMD-30569; -. DR EMDB; EMD-30570; -. DR EMDB; EMD-31474; -. DR EMDB; EMD-31475; -. DR EMDB; EMD-9840; -. DR EMDB; EMD-9841; -. DR EMDB; EMD-9842; -. DR SMR; P05198; -. DR BioGRID; 108285; 254. DR ComplexPortal; CPX-2716; Eukaryotic translation initiation factor 2 complex. DR CORUM; P05198; -. DR DIP; DIP-39418N; -. DR IntAct; P05198; 76. DR MINT; P05198; -. DR STRING; 9606.ENSP00000256383; -. DR BindingDB; P05198; -. DR ChEMBL; CHEMBL1255131; -. DR GlyCosmos; P05198; 4 sites, 1 glycan. 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; 9606-ENSP00000256383; -. DR PeptideAtlas; P05198; -. DR ProteomicsDB; 51824; -. DR Pumba; P05198; -. DR TopDownProteomics; P05198; -. DR Antibodypedia; 3181; 1061 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 AGR; HGNC:3265; -. 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; 4371132at2759; -. 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 Reactome; R-HSA-9833482; PKR-mediated signaling. DR SignaLink; P05198; -. DR SIGNOR; P05198; -. DR BioGRID-ORCS; 1965; 826 hits in 1137 CRISPR screens. DR EvolutionaryTrace; P05198; -. DR GeneWiki; EIF2S1; -. DR GenomeRNAi; 1965; -. DR Pharos; P05198; Tchem. DR PRO; PR:P05198; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P05198; Protein. DR Bgee; ENSG00000134001; Expressed in islet of Langerhans and 214 other cell types or tissues. DR ExpressionAtlas; P05198; baseline and differential. 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: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: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: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: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:2000676; P:positive regulation of type B pancreatic cell apoptotic process; IEA:Ensembl. DR GO; GO:0036490; P:regulation of translation in response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL. 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:1904373; P:response to kainic acid; IEA:Ensembl. 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 GO; GO:0006413; P:translational initiation; IDA:UniProt. DR CDD; cd04452; S1_IF2_alpha; 1. DR Gene3D; 3.30.70.1130; EIF_2_alpha; 1. DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1. DR IDEAL; IID00508; -. DR InterPro; IPR012340; NA-bd_OB-fold. 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; EUKARYOTIC TRANSLATION INITIATION FACTOR 2 SUBUNIT 1; 1. DR PANTHER; PTHR10602:SF0; EUKARYOTIC TRANSLATION INITIATION FACTOR 2 SUBUNIT 1; 1. DR Pfam; PF07541; EIF_2_alpha; 1. DR Pfam; PF00575; S1; 1. DR SMART; SM00316; S1; 1. DR SUPFAM; SSF110993; eIF-2-alpha, C-terminal domain; 1. DR SUPFAM; SSF116742; eIF2alpha middle domain-like; 1. DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 1. DR PROSITE; PS50126; S1; 1. DR Genevisible; P05198; HS. 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 //