ID EI2BA_HUMAN Reviewed; 305 AA. AC Q14232; A6NLY9; B4DGX0; Q3SXP4; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 27-MAR-2024, entry version 191. DE RecName: Full=Translation initiation factor eIF2B subunit alpha; DE AltName: Full=eIF2B GDP-GTP exchange factor subunit alpha; GN Name=EIF2B1; Synonyms=EIF2BA; 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] (ISOFORM 1). RA Torp A.; RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-35, 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 [8] 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 [9] RP IDENTIFICATION BY MASS SPECTROMETRY [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). RN [10] RP IDENTIFICATION BY 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 [11] RP FUNCTION, ACTIVITY REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, AND RP IDENTIFICATION IN THE EIF2B COMPLEX. RX PubMed=25858979; DOI=10.1126/science.aaa6986; RA Sekine Y., Zyryanova A., Crespillo-Casado A., Fischer P.M., Harding H.P., RA Ron D.; RT "Stress responses. Mutations in a translation initiation factor identify RT the target of a memory-enhancing compound."; RL Science 348:1027-1030(2015). RN [12] RP FUNCTION, AND IDENTIFICATION IN THE EIF2B COMPLEX. RX PubMed=27023709; DOI=10.1007/s10969-016-9203-3; RA Kashiwagi K., Shigeta T., Imataka H., Ito T., Yokoyama S.; RT "Expression, purification, and crystallization of Schizosaccharomyces pombe RT eIF2B."; RL J. Struct. Funct. Genomics 17:33-38(2016). RN [13] {ECO:0007744|PDB:6K71, ECO:0007744|PDB:6K72} RP STRUCTURE BY ELECTRON MICROSCOPY (4.30 ANGSTROMS) IN COMPLEX WITH THE EIF2 RP COMPLEX, FUNCTION, SUBUNIT, AND IDENTIFICATION IN THE EIF2B COMPLEX. 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). RN [14] RP VARIANT VWM1 TYR-208. RX PubMed=11835386; DOI=10.1002/ana.10112; RA van der Knaap M.S., Leegwater P.A.J., Koenst A.A.M., Visser A., Naidu S., RA Oudejans C.B.M., Schutgens R.B.H., Pronk J.C.; RT "Mutations in each of the five subunits of translation initiation factor RT eIF2B can cause leukoencephalopathy with vanishing white matter."; RL Ann. Neurol. 51:264-270(2002). RN [15] RP VARIANT VWM1 PHE-183. RX PubMed=15776425; DOI=10.1002/humu.9325; RA Ohlenbusch A., Henneke M., Brockmann K., Goerg M., Hanefeld F., RA Kohlschutter A., Gartner J.; RT "Identification of ten novel mutations in patients with eIF2B-related RT disorders."; RL Hum. Mutat. 25:411-411(2005). CC -!- FUNCTION: Acts as a component of the translation initiation factor 2B CC (eIF2B) complex, which catalyzes the exchange of GDP for GTP on CC eukaryotic initiation factor 2 (eIF2) gamma subunit (PubMed:25858979, CC PubMed:27023709, PubMed:31048492). 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 (PubMed:25858979, PubMed:31048492). CC {ECO:0000269|PubMed:25858979, ECO:0000269|PubMed:27023709, CC ECO:0000269|PubMed:31048492}. CC -!- ACTIVITY REGULATION: Activated by the chemical integrated stress CC response (ISR) inhibitor ISRIB which stimulates guanine nucleotide CC exchange factor activity for both phosphorylated and unphosphorylated CC eIF2. {ECO:0000269|PubMed:25858979}. 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:25858979, CC PubMed:27023709, PubMed:31048492). Within the complex, the hexameric CC regulatory complex resides at the center, with the two heterodimeric CC catalytic subcomplexes bound on opposite sides (PubMed:25858979, CC PubMed:31048492). {ECO:0000269|PubMed:25858979, CC ECO:0000269|PubMed:27023709, ECO:0000269|PubMed:31048492}. CC -!- INTERACTION: CC Q14232; Q9Y2D1: ATF5; NbExp=5; IntAct=EBI-491065, EBI-492509; CC Q14232; Q9BV19: C1orf50; NbExp=3; IntAct=EBI-491065, EBI-2874661; CC Q14232; Q14232: EIF2B1; NbExp=6; IntAct=EBI-491065, EBI-491065; CC Q14232; Q9H8Y8: GORASP2; NbExp=8; IntAct=EBI-491065, EBI-739467; CC Q14232; Q9NX70: MED29; NbExp=3; IntAct=EBI-491065, EBI-394656; CC Q14232; Q96HA8: NTAQ1; NbExp=7; IntAct=EBI-491065, EBI-741158; CC Q14232; Q7Z3Z2: RD3; NbExp=10; IntAct=EBI-491065, EBI-10257497; CC Q14232; Q8IWR1: TRIM59; NbExp=3; IntAct=EBI-491065, EBI-10262539; CC Q14232; Q8N7C3: TRIML2; NbExp=3; IntAct=EBI-491065, EBI-11059915; CC Q14232; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-491065, EBI-10180829; CC Q14232; Q01338: Adra2a; Xeno; NbExp=2; IntAct=EBI-491065, EBI-491073; CC Q14232; P30545: Adra2b; Xeno; NbExp=2; IntAct=EBI-491065, EBI-491084; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q9USP0}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q14232-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14232-2; Sequence=VSP_055469, VSP_055470; CC -!- DISEASE: Leukoencephalopathy with vanishing white matter 1 (VWM1) CC [MIM:603896]: An autosomal recessive brain disease characterized by CC neurological features including progressive cerebellar ataxia, CC spasticity, and cognitive deficits. Brain imaging shows abnormal white CC matter that vanishes over time and is replaced by cerebrospinal fluid. CC Disease severity ranges from fatal infantile forms to adult forms CC without neurological deterioration. The disease is progressive with, in CC most individuals, additional episodes of rapid deterioration following CC febrile infections or minor head trauma. Death may occurs after a CC variable period after disease onset, usually following an episode of CC fever and coma. A subset of affected females with milder forms of the CC disease who survive to adolescence exhibit ovarian dysfunction. This CC variant of the disorder is called ovarioleukodystrophy. CC {ECO:0000269|PubMed:11835386, ECO:0000269|PubMed:15776425}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the eIF-2B alpha/beta/delta subunits family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Mendelian genes eukaryotic translation initiation CC factor 2B, subunit 1 alpha, 26kDa (EIF2B1); Note=Leiden Open Variation CC Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/EIF2B1"; 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; X95648; CAA64950.1; -; mRNA. DR EMBL; AK294815; BAG57931.1; -; mRNA. DR EMBL; CR456831; CAG33112.1; -; mRNA. DR EMBL; AC117503; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471054; EAW98424.1; -; Genomic_DNA. DR EMBL; BC103763; AAI03764.1; -; mRNA. DR EMBL; BC104188; AAI04189.1; -; mRNA. DR EMBL; BC104189; AAI04190.1; -; mRNA. DR CCDS; CCDS31924.1; -. [Q14232-1] DR RefSeq; NP_001405.1; NM_001414.3. [Q14232-1] DR PDB; 3ECS; X-ray; 2.65 A; A/B/C/D/E/F/G/H=1-305. DR PDB; 6CAJ; EM; 2.80 A; G/H=1-305. DR PDB; 6EZO; EM; 4.10 A; A/B=1-305. DR PDB; 6K71; EM; 4.30 A; A/B=1-305. DR PDB; 6K72; EM; 4.60 A; A/B=1-305. DR PDB; 6O81; EM; 3.21 A; G/H=1-305. DR PDB; 6O85; EM; 3.03 A; G/H=1-305. DR PDB; 6O9Z; EM; 3.03 A; G/H=1-305. DR PDB; 7D43; EM; 4.30 A; A/B=1-305. DR PDB; 7D44; EM; 4.00 A; A/B=1-305. DR PDB; 7D45; EM; 3.80 A; A/B=1-305. DR PDB; 7D46; EM; 4.00 A; A/B=1-305. DR PDB; 7F64; EM; 2.42 A; A/B=1-305. DR PDB; 7F66; EM; 2.76 A; A/B=1-305. DR PDB; 7F67; EM; 3.59 A; A/B=1-305. DR PDB; 7KMA; X-ray; 2.70 A; A/B/C/D/E/F/G/H=1-305. DR PDB; 7KMF; EM; 2.91 A; G/H=1-305. DR PDB; 7L70; EM; 2.80 A; G/H=2-305. DR PDB; 7L7G; EM; 3.00 A; G/H=1-305. DR PDB; 7RLO; EM; 2.60 A; G/H=1-305. DR PDB; 7TRJ; EM; 2.80 A; G/H=1-305. DR PDB; 7VLK; EM; 2.27 A; A/B=1-305. DR PDB; 8TQZ; EM; 2.90 A; G/H=2-305. DR PDBsum; 3ECS; -. DR PDBsum; 6CAJ; -. DR PDBsum; 6EZO; -. DR PDBsum; 6K71; -. DR PDBsum; 6K72; -. DR PDBsum; 6O81; -. DR PDBsum; 6O85; -. DR PDBsum; 6O9Z; -. DR PDBsum; 7D43; -. DR PDBsum; 7D44; -. DR PDBsum; 7D45; -. DR PDBsum; 7D46; -. DR PDBsum; 7F64; -. DR PDBsum; 7F66; -. DR PDBsum; 7F67; -. DR PDBsum; 7KMA; -. DR PDBsum; 7KMF; -. DR PDBsum; 7L70; -. DR PDBsum; 7L7G; -. DR PDBsum; 7RLO; -. DR PDBsum; 7TRJ; -. DR PDBsum; 7VLK; -. DR PDBsum; 8TQZ; -. DR AlphaFoldDB; Q14232; -. DR EMDB; EMD-0649; -. DR EMDB; EMD-0651; -. DR EMDB; EMD-0664; -. DR EMDB; EMD-22924; -. DR EMDB; EMD-23209; -. DR EMDB; EMD-24535; -. DR EMDB; EMD-26098; -. DR EMDB; EMD-30568; -. DR EMDB; EMD-30569; -. DR EMDB; EMD-30570; -. DR EMDB; EMD-30571; -. DR EMDB; EMD-31472; -. DR EMDB; EMD-31474; -. DR EMDB; EMD-31475; -. DR EMDB; EMD-32023; -. DR EMDB; EMD-4162; -. DR EMDB; EMD-7442; -. DR EMDB; EMD-9840; -. DR EMDB; EMD-9841; -. DR EMDB; EMD-9842; -. DR SMR; Q14232; -. DR BioGRID; 108286; 141. DR CORUM; Q14232; -. DR IntAct; Q14232; 67. DR MINT; Q14232; -. DR STRING; 9606.ENSP00000416250; -. DR GlyGen; Q14232; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q14232; -. DR MetOSite; Q14232; -. DR PhosphoSitePlus; Q14232; -. DR SwissPalm; Q14232; -. DR BioMuta; EIF2B1; -. DR DMDM; 2494303; -. DR EPD; Q14232; -. DR jPOST; Q14232; -. DR MassIVE; Q14232; -. DR MaxQB; Q14232; -. DR PaxDb; 9606-ENSP00000416250; -. DR PeptideAtlas; Q14232; -. DR ProteomicsDB; 4168; -. DR ProteomicsDB; 59934; -. [Q14232-1] DR Pumba; Q14232; -. DR Antibodypedia; 31819; 183 antibodies from 27 providers. DR DNASU; 1967; -. DR Ensembl; ENST00000424014.7; ENSP00000416250.2; ENSG00000111361.13. [Q14232-1] DR Ensembl; ENST00000537073.1; ENSP00000444183.1; ENSG00000111361.13. [Q14232-2] DR GeneID; 1967; -. DR KEGG; hsa:1967; -. DR MANE-Select; ENST00000424014.7; ENSP00000416250.2; NM_001414.4; NP_001405.1. DR UCSC; uc001ufm.4; human. [Q14232-1] DR AGR; HGNC:3257; -. DR CTD; 1967; -. DR DisGeNET; 1967; -. DR GeneCards; EIF2B1; -. DR GeneReviews; EIF2B1; -. DR HGNC; HGNC:3257; EIF2B1. DR HPA; ENSG00000111361; Low tissue specificity. DR MalaCards; EIF2B1; -. DR MIM; 603896; phenotype. DR MIM; 606686; gene. DR neXtProt; NX_Q14232; -. DR OpenTargets; ENSG00000111361; -. DR Orphanet; 157713; Congenital or early infantile CACH syndrome. DR Orphanet; 99854; Cree leukoencephalopathy. DR Orphanet; 157719; Juvenile or adult CACH syndrome. DR Orphanet; 157716; Late infantile CACH syndrome. DR Orphanet; 99853; Ovarioleukodystrophy. DR PharmGKB; PA27688; -. DR VEuPathDB; HostDB:ENSG00000111361; -. DR eggNOG; KOG1466; Eukaryota. DR GeneTree; ENSGT00550000074853; -. DR HOGENOM; CLU_016218_0_2_1; -. DR InParanoid; Q14232; -. DR OMA; GDWESCK; -. DR OrthoDB; 51607at2759; -. DR PhylomeDB; Q14232; -. DR TreeFam; TF101505; -. DR PathwayCommons; Q14232; -. DR Reactome; R-HSA-72731; Recycling of eIF2:GDP. DR SignaLink; Q14232; -. DR SIGNOR; Q14232; -. DR BioGRID-ORCS; 1967; 555 hits in 1164 CRISPR screens. DR ChiTaRS; EIF2B1; human. DR EvolutionaryTrace; Q14232; -. DR GeneWiki; EIF2B1; -. DR GenomeRNAi; 1967; -. DR Pharos; Q14232; Tbio. DR PRO; PR:Q14232; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q14232; Protein. DR Bgee; ENSG00000111361; Expressed in oocyte and 193 other cell types or tissues. DR ExpressionAtlas; Q14232; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005851; C:eukaryotic translation initiation factor 2B complex; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003743; F:translation initiation factor activity; IEA:UniProtKB-KW. DR GO; GO:0002183; P:cytoplasmic translational initiation; IDA:UniProtKB. DR GO; GO:0014003; P:oligodendrocyte development; IMP:UniProtKB. DR GO; GO:0009749; P:response to glucose; ISS:UniProtKB. DR GO; GO:0009408; P:response to heat; ISS:UniProtKB. DR GO; GO:0043434; P:response to peptide hormone; ISS:UniProtKB. DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0006413; P:translational initiation; IDA:UniProtKB. 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. DR Genevisible; Q14232; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Disease variant; Initiation factor; Leukodystrophy; Protein biosynthesis; KW Reference proteome. FT CHAIN 1..305 FT /note="Translation initiation factor eIF2B subunit alpha" FT /id="PRO_0000156055" FT MOD_RES 35 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 162..222 FT /note="KKMAKALCHLNVPVTVVLDAAVGYIMEKADLVIVGAEGVVENGGIINKIGTN FT QMAVCAKAQ -> QVPFCSVMCPAIILQSKLRITVQQDQNQNVPPACQQSALPFIVPFP FT AFGRKITEFAAGRSI (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055469" FT VAR_SEQ 223..305 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055470" FT VARIANT 183 FT /note="V -> F (in VWM1; dbSNP:rs863225048)" FT /evidence="ECO:0000269|PubMed:15776425" FT /id="VAR_068450" FT VARIANT 208 FT /note="N -> Y (in VWM1; dbSNP:rs113994007)" FT /evidence="ECO:0000269|PubMed:11835386" FT /id="VAR_015404" FT HELIX 3..16 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 17..20 FT /evidence="ECO:0007829|PDB:7L70" FT HELIX 22..35 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 46..59 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 63..82 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 86..115 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 116..118 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 123..126 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 132..143 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 148..153 FT /evidence="ECO:0007829|PDB:7VLK" FT TURN 156..159 FT /evidence="ECO:0007829|PDB:7F64" FT HELIX 160..170 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 175..178 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 180..182 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 183..186 FT /evidence="ECO:0007829|PDB:7VLK" FT TURN 187..189 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 191..195 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 198..200 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 202..204 FT /evidence="ECO:0007829|PDB:7L70" FT STRAND 206..209 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 212..221 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 226..229 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 232..234 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 241..243 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 248..251 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 272..276 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 278..280 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 283..286 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 294..303 FT /evidence="ECO:0007829|PDB:7VLK" SQ SEQUENCE 305 AA; 33712 MW; 91A915FF1B80B780 CRC64; MDDKELIEYF KSQMKEDPDM ASAVAAIRTL LEFLKRDKGE TIQGLRANLT SAIETLCGVD SSVAVSSGGE LFLRFISLAS LEYSDYSKCK KIMIERGELF LRRISLSRNK IADLCHTFIK DGATILTHAY SRVVLRVLEA AVAAKKRFSV YVTESQPDLS GKKMAKALCH LNVPVTVVLD AAVGYIMEKA DLVIVGAEGV VENGGIINKI GTNQMAVCAK AQNKPFYVVA ESFKFVRLFP LNQQDVPDKF KYKADTLKVA QTGQDLKEEH PWVDYTAPSL ITLLFTDLGV LTPSAVSDEL IKLYL //