LOCUS       NM_001414               2397 bp    mRNA    linear   PRI 28-APR-2025
DEFINITION  Homo sapiens eukaryotic translation initiation factor 2B subunit
            alpha (EIF2B1), mRNA.
ACCESSION   NM_001414
VERSION     NM_001414.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2397)
  AUTHORS   Wuerth,J.D. and Weber,F.
  TITLE     Shielding the mRNA-translation factor eIF2B from inhibitory p-eIF2
            as a viral strategy to evade protein kinase R-mediated innate
            immunity
  JOURNAL   Curr Opin Immunol 78, 102251 (2022)
   PUBMED   36242870
  REMARK    GeneRIF: Shielding the mRNA-translation factor eIF2B from
            inhibitory p-eIF2 as a viral strategy to evade protein kinase
            R-mediated innate immunity.
            Review article
REFERENCE   2  (bases 1 to 2397)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   3  (bases 1 to 2397)
  AUTHORS   De Franco,E., Caswell,R., Johnson,M.B., Wakeling,M.N., Zung,A.,
            Dung,V.C., Bich Ngoc,C.T., Goonetilleke,R., Vivanco Jury,M.,
            El-Khateeb,M., Ellard,S., Flanagan,S.E., Ron,D. and Hattersley,A.T.
  TITLE     De Novo Mutations in EIF2B1 Affecting eIF2 Signaling Cause
            Neonatal/Early-Onset Diabetes and Transient Hepatic Dysfunction
  JOURNAL   Diabetes 69 (3), 477-483 (2020)
   PUBMED   31882561
  REMARK    GeneRIF: Our results establish de novo EIF2B1 mutations as a novel
            cause of permanent diabetes and liver dysfunction. These findings
            confirm the importance of cell stress regulation for beta-cells and
            highlight EIF2B1's fundamental role within this pathway.
REFERENCE   4  (bases 1 to 2397)
  AUTHORS   Fragoza,R., Das,J., Wierbowski,S.D., Liang,J., Tran,T.N., Liang,S.,
            Beltran,J.F., Rivera-Erick,C.A., Ye,K., Wang,T.Y., Yao,L., Mort,M.,
            Stenson,P.D., Cooper,D.N., Wei,X., Keinan,A., Schimenti,J.C.,
            Clark,A.G. and Yu,H.
  TITLE     Extensive disruption of protein interactions by genetic variants
            across the allele frequency spectrum in human populations
  JOURNAL   Nat Commun 10 (1), 4141 (2019)
   PUBMED   31515488
  REMARK    Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2397)
  AUTHORS   Yang,W. and Hinnebusch,A.G.
  TITLE     Identification of a regulatory subcomplex in the guanine nucleotide
            exchange factor eIF2B that mediates inhibition by phosphorylated
            eIF2
  JOURNAL   Mol Cell Biol 16 (11), 6603-6616 (1996)
   PUBMED   8887689
REFERENCE   6  (bases 1 to 2397)
  AUTHORS   Welsh,G.I., Miyamoto,S., Price,N.T., Safer,B. and Proud,C.G.
  TITLE     T-cell activation leads to rapid stimulation of translation
            initiation factor eIF2B and inactivation of glycogen synthase
            kinase-3
  JOURNAL   J Biol Chem 271 (19), 11410-11413 (1996)
   PUBMED   8626696
REFERENCE   7  (bases 1 to 2397)
  AUTHORS   Flowers,K.M., Mellor,H., Kimball,S.R. and Jefferson,L.S.
  TITLE     Structure and sequence of the gene encoding the alpha-subunit of
            rat translation initiation factor-2B
  JOURNAL   Biochim Biophys Acta 1264 (2), 163-167 (1995)
   PUBMED   7495858
REFERENCE   8  (bases 1 to 2397)
  AUTHORS   Vanderver,A., Tonduti,D., Schiffmann,R., Schmidt,J. and van der
            Knaap,M.S.
  TITLE     Leukodystrophy Overview - RETIRED CHAPTER, FOR HISTORICAL REFERENCE
            ONLY
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   24501781
REFERENCE   9  (bases 1 to 2397)
  AUTHORS   van der Knaap,M.S., Fogli,A., Boespflug-Tanguy,O., Abbink,T.E.M.
            and Schiffmann,R.
  TITLE     Childhood Ataxia with Central Nervous System Hypomyelination /
            Vanishing White Matter
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301435
REFERENCE   10 (bases 1 to 2397)
  AUTHORS   Hershey,J.W.
  TITLE     Translational control in mammalian cells
  JOURNAL   Annu Rev Biochem 60, 717-755 (1991)
   PUBMED   1883206
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff in
            collaboration with Francesco Amaldi. The reference sequence was
            derived from AC117503.8.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_001414.3.
            
            Summary: This gene encodes one of five subunits of eukaryotic
            translation initiation factor 2B (EIF2B), a GTP exchange factor for
            eukaryotic initiation factor 2 and an essential regulator for
            protein synthesis. Mutations in this gene and the genes encoding
            other EIF2B subunits have been associated with leukoencephalopathy
            with vanishing white matter. [provided by RefSeq, Oct 2009].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803614.5290.1,
                                           SRR1660807.189405.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000424014.7/ ENSP00000416250.2
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-142               AC117503.8         192823-192964
            143-244             AC117503.8         194063-194164
            245-381             AC117503.8         195976-196112
            382-498             AC117503.8         196224-196340
            499-611             AC117503.8         199353-199465
            612-680             AC117503.8         200016-200084
            681-756             AC117503.8         201647-201722
            757-882             AC117503.8         203748-203873
            883-2397            AC117503.8         204589-206103
FEATURES             Location/Qualifiers
     source          1..2397
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q24.31"
     gene            1..2397
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /note="eukaryotic translation initiation factor 2B subunit
                     alpha"
                     /db_xref="GeneID:1967"
                     /db_xref="HGNC:HGNC:3257"
                     /db_xref="MIM:606686"
     exon            1..142
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /inference="alignment:Splign:2.1.0"
     CDS             130..1047
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /note="eukaryotic translation initiation factor 2B,
                     subunit 1 alpha, 26kDa; eIF-2B GDP-GTP exchange factor
                     subunit alpha; eIF2B GDP-GTP exchange factor subunit
                     alpha"
                     /codon_start=1
                     /product="translation initiation factor eIF2B subunit
                     alpha"
                     /protein_id="NP_001405.1"
                     /db_xref="CCDS:CCDS31924.1"
                     /db_xref="GeneID:1967"
                     /db_xref="HGNC:HGNC:3257"
                     /db_xref="MIM:606686"
                     /translation="MDDKELIEYFKSQMKEDPDMASAVAAIRTLLEFLKRDKGETIQG
                     LRANLTSAIETLCGVDSSVAVSSGGELFLRFISLASLEYSDYSKCKKIMIERGELFLR
                     RISLSRNKIADLCHTFIKDGATILTHAYSRVVLRVLEAAVAAKKRFSVYVTESQPDLS
                     GKKMAKALCHLNVPVTVVLDAAVGYIMEKADLVIVGAEGVVENGGIINKIGTNQMAVC
                     AKAQNKPFYVVAESFKFVRLFPLNQQDVPDKFKYKADTLKVAQTGQDLKEEHPWVDYT
                     APSLITLLFTDLGVLTPSAVSDELIKLYL"
     exon            143..244
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /inference="alignment:Splign:2.1.0"
     exon            245..381
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /inference="alignment:Splign:2.1.0"
     exon            382..498
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /inference="alignment:Splign:2.1.0"
     exon            499..611
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /inference="alignment:Splign:2.1.0"
     exon            612..680
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /inference="alignment:Splign:2.1.0"
     exon            681..756
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /inference="alignment:Splign:2.1.0"
     exon            757..882
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /inference="alignment:Splign:2.1.0"
     exon            883..2397
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1757..1762
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /note="hexamer: AATAAA"
     polyA_site      1780
                     /gene="EIF2B1"
                     /gene_synonym="EIF2B; EIF2BA; EIF2Balpha; VWM1"
                     /note="major polyA site"
ORIGIN      
        1 gcgccggaag tggggtgcgg aggtgtgcag cgcgctgtca gactggctcg caggcggcgc
       61 ggccggcgga cccgttcgag acagcgcggg cggctcgggt cccctggggc tccgcagcag
      121 gaggacgcca tggacgacaa ggagttaatt gaatacttta agtctcagat gaaagaagat
      181 cctgacatgg cctcagcagt ggctgccatc cggacgttgc tggagttctt gaagagagat
      241 aaaggggaga caatccaggg tctgagggcg aatctcacca gtgccataga aaccctgtgt
      301 ggtgtggact cctctgtggc agtgtcctct ggcggggagc tcttcctccg cttcatcagt
      361 cttgcctccc tggaatactc cgattactcc aaatgtaaaa agatcatgat tgagcgggga
      421 gaactttttc tcaggagaat atcactgtca agaaacaaaa ttgcagatct gtgccatact
      481 ttcatcaaag atggagcgac aatattgact cacgcctact ccagagtggt cctgagagtc
      541 ctggaagcag ccgtggcggc caagaagcga tttagtgtat acgtcacaga gtcacagcct
      601 gatttgtcag gtaagaaaat ggccaaagcc ctctgccacc tcaacgtccc tgtcactgtg
      661 gtgctagatg ctgctgtcgg ctacatcatg gagaaagcag atcttgtcat agttggtgct
      721 gaaggagttg ttgaaaacgg aggaattatt aacaagattg gaaccaacca gatggctgtg
      781 tgtgccaaag cacagaacaa acctttctat gtggttgcag aaagtttcaa gtttgtccgg
      841 ctctttccac taaaccagca agacgtccca gataagttta agtataaggc agacactctc
      901 aaggtcgcgc agactggaca agacctcaaa gaggagcatc cgtgggtcga ctacactgcc
      961 ccttccttaa tcactctgct gtttacagac ctgggcgtgc tgacaccctc agcagtcagc
     1021 gatgagctca tcaagctcta tctgtaacct gtgagccctt tcctgccaag gtgcagctta
     1081 cgtagttgag gcagggtgag tagctgcttg acaccccagt gagtcaggcc aaaactgaga
     1141 tgtgtttaat gaagatttat ggagtaagga cttaaaatca tacatcttgg agaacctttc
     1201 ttactcattt cagtcccatc taaaaatgtg tcagctattc taaatcccaa cttaaattgt
     1261 tcttacggtt tctagaaact ttccttttca gtttccagaa atacaagtta gataattggc
     1321 tacttaactg atgaaagatg agcccaagtc cacctgtctt catcctcccc tgcactccag
     1381 actgatctgc ctaaagcacg cgagatgcag gcgaaaagca gccacacccc tctgccacaa
     1441 atgaccaaca gctggtcagg acgttacacg cggtgccttg taagaggcaa gaaacacttg
     1501 ctgaatctgc atctggcttc cagtggtaag cacattcctc agcaggatca agccaaacag
     1561 taaaaactac caagagaaca cgaggaaggc agaaacgatg tttagcaaca gtattctgca
     1621 tggttcactg cttaagaaaa tgccttctgg aatatttgta aactgaaatt ctgtatgtgt
     1681 aagagatgtt taaatatgtt tgggtcctaa acagcttttt aaaattatac ttgggaataa
     1741 attcagcatc ttttcaaata aactctatga aagacgctga tgtggtgttg catcaatact
     1801 gcaagctgac caggccatct aggggaaaac actgtccagc tacatttaca cacttaagac
     1861 ccaggcaatc aggacaccat ttattcaaca ggaggcataa aaactataat tctctttccc
     1921 ggaatatgac ttaatccctc tgtttttcag ctattcacca ataaaacaat actgtgacta
     1981 ttaacacaga aaaaccccag cacattagcc acccctgcag gacatcaaag gataactgaa
     2041 gcccagggcc aagcacattc aggaggtcaa atgcctgaag atactgagga atggttttga
     2101 aaatcagaag tcaagaagac ttctgtatct ttatgtttaa aaataactat aaaatagcct
     2161 cagaaaaaag agcttatata tatatatata tatatatata tatatatata tatatatata
     2221 taatatgtac atatgtctat atgtgaccca tcatgataaa tactgacatc tattatttac
     2281 actcaaataa ttttacattt tcttctgtta gactactcca agactggaat tgttttgttt
     2341 tgttgttttt aatgagaggg tctcgctgtg ttcccaggct ggtcttgaac tcctggg
//
