LOCUS       NM_001034116            1644 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens eukaryotic translation initiation factor 2B subunit
            delta (EIF2B4), transcript variant 2, mRNA.
ACCESSION   NM_001034116
VERSION     NM_001034116.2
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 1644)
  AUTHORS   Shivaram,S., Nagappa,M., Seshagiri,D.V., Saini,J., Govindaraj,P.,
            Sinha,S., Bindu,P.S. and Taly,A.B.
  TITLE     Leukodystrophy Due to eIF2B Mutations in Adults
  JOURNAL   Can J Neurol Sci 49 (5), 708-712 (2022)
   PUBMED   34663487
  REMARK    GeneRIF: Leukodystrophy Due to eIF2B Mutations in Adults.
REFERENCE   2  (bases 1 to 1644)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   3  (bases 1 to 1644)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   4  (bases 1 to 1644)
  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   5  (bases 1 to 1644)
  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 1644)
  AUTHORS   Price,N.T., Mellor,H., Craddock,B.L., Flowers,K.M., Kimball,S.R.,
            Wilmer,T., Jefferson,L.S. and Proud,C.G.
  TITLE     eIF2B, the guanine nucleotide-exchange factor for eukaryotic
            initiation factor 2. Sequence conservation between the alpha, beta
            and delta subunits of eIF2B from mammals and yeast
  JOURNAL   Biochem J 318 (Pt 2) (Pt 2), 637-643 (1996)
   PUBMED   8929216
REFERENCE   7  (bases 1 to 1644)
  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   8  (bases 1 to 1644)
  AUTHORS   Henderson,R.A., Krissansen,G.W., Yong,R.Y., Leung,E., Watson,J.D.
            and Dholakia,J.N.
  TITLE     The delta-subunit of murine guanine nucleotide exchange factor
            eIF-2B. Characterization of cDNAs predicts isoforms differing at
            the amino-terminal end
  JOURNAL   J Biol Chem 269 (48), 30517-30523 (1994)
   PUBMED   7982969
REFERENCE   9  (bases 1 to 1644)
  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   10 (bases 1 to 1644)
  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
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from JQ991007.1, BC091502.1 and
            AF112207.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 27, 2019 this sequence version replaced NM_001034116.1.
            
            Summary: Eukaryotic initiation factor 2B (EIF2B), which is
            necessary for protein synthesis, is a GTP exchange factor composed
            of five different subunits. The protein encoded by this gene is the
            fourth, or delta, subunit. Defects in this gene are a cause of
            leukoencephalopathy with vanishing white matter (VWM) and
            ovarioleukodystrophy. Multiple transcript variants encoding
            different isoforms have been found for this gene. [provided by
            RefSeq, Jul 2008].
            
            Transcript Variant: This variant (2) differs in the 5' UTR and
            coding sequence compared to variant 4. The resulting isoform (2)
            has a shorter and distinct N-terminus compared to isoform 4.
            
            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 :: AF112207.1, BC091502.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000347454.9/ ENSP00000233552.6
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-8                 JQ991007.1         120-127
            9-1634              BC091502.1         1-1626
            1635-1644           AF112207.1         1630-1639
FEATURES             Location/Qualifiers
     source          1..1644
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p23.3"
     gene            1..1644
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /note="eukaryotic translation initiation factor 2B subunit
                     delta"
                     /db_xref="GeneID:8890"
                     /db_xref="HGNC:HGNC:3260"
                     /db_xref="MIM:606687"
     exon            1..55
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     CDS             25..1596
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /note="isoform 2 is encoded by transcript variant 2;
                     translation initiation factor eIF-2b delta subunit;
                     translation initiation factor eIF-2B subunit delta; eIF-2B
                     GDP-GTP exchange factor subunit delta; eukaryotic
                     translation initiation factor 2B subunit 4 delta;
                     eukaryotic translation initiation factor 2B, subunit 4
                     delta, 67kDa; eIF2B GDP-GTP exchange factor subunit delta;
                     translation initiation factor eIF2B subunit delta"
                     /codon_start=1
                     /product="translation initiation factor eIF2B subunit
                     delta isoform 2"
                     /protein_id="NP_001029288.1"
                     /db_xref="CCDS:CCDS33164.1"
                     /db_xref="GeneID:8890"
                     /db_xref="HGNC:HGNC:3260"
                     /db_xref="MIM:606687"
                     /translation="MAAVAVAVREDSGSGMKAELPPGPGAVGREMTKEEKLQLRKEKK
                     QQKKKRKEEKGAEPETGSAVSAAQCQVGPTRELPESGIQLGTPREKVPAGRSKAELRA
                     ERRAKQEAERALKQARKGEQGGPPPKASPSTAGETPSGVKRLPEYPQVDDLLLRRLVK
                     KPERQQVPTRKDYGSKVSLFSHLPQYSRQNSLTQFMSIPSSVIHPAMVRLGLQYSQGL
                     VSGSNARCIALLRALQQVIQDYTTPPNEELSRDLVNKLKPYMSFLTQCRPLSASMHNA
                     IKFLNKEITSVGSSKREEEAKSELRAAIDRYVQEKIVLAAQAISRFAYQKISNGDVIL
                     VYGCSSLVSRILQEAWTEGRRFRVVVVDSRPWLEGRHTLRSLVHAGVPASYLLIPAAS
                     YVLPEVSKVLLGAHALLANGSVMSRVGTAQLALVARAHNVPVLVCCETYKFCERVQTD
                     AFVSNELDDPDDLQCKRGEHVALANWQNHASLRLLNLVYDVTPPELVDLVITELGMIP
                     CSSVPVVLRVKSSDQ"
     exon            56..99
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            100..235
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            236..442
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            443..522
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            523..614
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            615..729
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            730..806
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            807..909
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            910..1037
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            1038..1215
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            1216..1396
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     exon            1397..1644
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1615..1620
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /note="hexamer: AATAAA"
     polyA_site      1644
                     /gene="EIF2B4"
                     /gene_synonym="EIF-2B; EIF2B; EIF2Bdelta; VWM4"
                     /note="major polyA site"
ORIGIN      
        1 gggcggagcc taggactgag ggcgatggct gctgtggccg tggctgttcg cgaggactcg
       61 ggatccggga tgaaggcgga gcttccccct gggcctgggg cagtggggag ggaaatgacc
      121 aaagaagaaa agctgcagct tcggaaggaa aagaaacagc agaagaagaa acggaaggaa
      181 gaaaaggggg cagaaccaga gactggctct gctgtatctg cagcccaatg tcaagtaggc
      241 ccaaccagag aactgccaga atcgggcatt cagttgggca ctcctcggga gaaagttcca
      301 gctggtcgga gtaaggccga acttcgggct gagcgtcgag ccaagcagga ggccgagcgg
      361 gccctgaaac aggcaagaaa aggggaacaa ggaggaccac ctcctaaggc cagccccagc
      421 acagctggag aaaccccctc aggagtgaag cgtctccctg agtaccctca ggttgatgac
      481 ctacttctga gaaggcttgt taaaaaacca gagcgtcaac aggttcctac acgaaaggat
      541 tatggatcca aagtcagtct cttctctcac ctaccccagt acagcagaca aaactctctg
      601 acccagttta tgagcatccc atcctctgtg atccacccag ccatggtgcg actcggcctg
      661 cagtactccc agggcctggt cagtggctcc aatgcccggt gtattgccct gcttcgtgcc
      721 ttgcagcagg tgattcagga ttacacaaca ccgcctaatg aagaactctc cagggatcta
      781 gtgaataaac taaaacccta catgagcttc ctgactcagt gccgtcccct gtcagcgagc
      841 atgcacaacg ccatcaagtt ccttaacaag gaaatcacca gtgtgggcag ttccaagcgg
      901 gaagaggagg ccaagtcaga acttcgagca gccattgatc ggtatgtgca agagaagatt
      961 gtgctagcag ctcaggcaat ttcacgcttt gcttaccaga agatcagtaa tggagatgtg
     1021 atcctggtat atggatgctc atctctggta tcacgaattc ttcaggaggc ttggacagag
     1081 ggccggcggt ttcgggtggt agtggtggac agccggccat ggctggaagg aaggcacaca
     1141 ctacgttctc tagtccatgc tggtgtccca gcctcctacc tgctgattcc tgcagcctcc
     1201 tatgtgctcc cagaggtttc caaggtgcta ttgggagctc atgcactctt ggccaacggg
     1261 tctgtgatgt cacgggtagg gacagcacag ttagccctgg tggctcgagc ccataatgta
     1321 ccagtgctgg tttgctgtga aacatacaag ttctgtgagc gtgtgcagac tgatgccttt
     1381 gtctctaatg agctagatga ccctgatgat ctgcaatgta agcggggaga acatgttgcg
     1441 ctggctaact ggcagaacca cgcatcccta cggttgttga atctagtcta tgatgtgact
     1501 cccccagagc ttgtggatct ggtgatcacg gagctgggga tgatcccttg cagttctgta
     1561 cctgttgttc tacgagtcaa gagcagtgac cagtgacggg ggaaacacag ggttaataaa
     1621 tgccatactc cctaccctca gcaa
//
