LOCUS       NM_014413               4411 bp    mRNA    linear   PRI 27-JUL-2024
DEFINITION  Homo sapiens eukaryotic translation initiation factor 2 alpha
            kinase 1 (EIF2AK1), transcript variant 1, mRNA.
ACCESSION   NM_014413
VERSION     NM_014413.4
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 4411)
  AUTHORS   Chakrabarty,Y., Yang,Z., Chen,H. and Chan,D.C.
  TITLE     The HRI branch of the integrated stress response selectively
            triggers mitophagy
  JOURNAL   Mol Cell 84 (6), 1090-1100 (2024)
   PUBMED   38340717
REFERENCE   2  (bases 1 to 4411)
  AUTHORS   Yang,J., Baron,K.R., Pride,D.E., Schneemann,A., Guo,X., Chen,W.,
            Song,A.S., Aviles,G., Kampmann,M., Wiseman,R.L. and Lander,G.C.
  TITLE     DELE1 oligomerization promotes integrated stress response
            activation
  JOURNAL   Nat Struct Mol Biol 30 (9), 1295-1302 (2023)
   PUBMED   37550454
REFERENCE   3  (bases 1 to 4411)
  AUTHORS   Adema,V., Ma,F., Kanagal-Shamanna,R., Thongon,N.,
            Montalban-Bravo,G., Yang,H., Peslak,S.A., Wang,F., Acha,P.,
            Sole,F., Lockyer,P., Cassari,M., Maciejewski,J.P., Visconte,V.,
            Ganan-Gomez,I., Song,Y., Bueso-Ramos,C., Pellegrini,M., Tan,T.M.,
            Bejar,R., Carew,J.S., Halene,S., Santini,V., Al-Atrash,G.,
            Clise-Dwyer,K., Garcia-Manero,G., Blobel,G.A. and Colla,S.
  TITLE     Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell
            Production in SF3B1-Mutant Myelodysplastic Syndromes With Ringed
            Sideroblasts
  JOURNAL   Blood Cancer Discov 3 (6), 554-567 (2022)
   PUBMED   35926182
  REMARK    GeneRIF: Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood
            Cell Production in SF3B1-Mutant Myelodysplastic Syndromes With
            Ringed Sideroblasts.
REFERENCE   4  (bases 1 to 4411)
  AUTHORS   Girardin,S.E., Cuziol,C., Philpott,D.J. and Arnoult,D.
  TITLE     The eIF2alpha kinase HRI in innate immunity, proteostasis, and
            mitochondrial stress
  JOURNAL   FEBS J 288 (10), 3094-3107 (2021)
   PUBMED   32892501
  REMARK    GeneRIF: The eIF2alpha kinase HRI in innate immunity, proteostasis,
            and mitochondrial stress.
            Review article
REFERENCE   5  (bases 1 to 4411)
  AUTHORS   Mukherjee,T., Ramaglia,V., Abdel-Nour,M., Bianchi,A.A.,
            Tsalikis,J., Chau,H.N., Kalia,S.K., Kalia,L.V., Chen,J.J.,
            Arnoult,D., Gommerman,J.L., Philpott,D.J. and Girardin,S.E.
  TITLE     The eIF2alpha kinase HRI triggers the autophagic clearance of
            cytosolic protein aggregates
  JOURNAL   J Biol Chem 296, 100050 (2021)
   PUBMED   33168630
  REMARK    GeneRIF: The eIF2alpha kinase HRI triggers the autophagic clearance
            of cytosolic protein aggregates.
REFERENCE   6  (bases 1 to 4411)
  AUTHORS   Shao,J., Grammatikakis,N., Scroggins,B.T., Uma,S., Huang,W.,
            Chen,J.J., Hartson,S.D. and Matts,R.L.
  TITLE     Hsp90 regulates p50(cdc37) function during the biogenesis of the
            activeconformation of the heme-regulated eIF2 alpha kinase
  JOURNAL   J Biol Chem 276 (1), 206-214 (2001)
   PUBMED   11036079
REFERENCE   7  (bases 1 to 4411)
  AUTHORS   Hwang,S.Y., Kim,M.K. and Kim,J.C.
  TITLE     Cloning of hHRI, human heme-regulated eukaryotic initiation factor
            2alpha kinase: down-regulated in epithelial ovarian cancers
  JOURNAL   Mol Cells 10 (5), 584-591 (2000)
   PUBMED   11101152
REFERENCE   8  (bases 1 to 4411)
  AUTHORS   Simpson,J.C., Wellenreuther,R., Poustka,A., Pepperkok,R. and
            Wiemann,S.
  TITLE     Systematic subcellular localization of novel proteins identified by
            large-scale cDNA sequencing
  JOURNAL   EMBO Rep 1 (3), 287-292 (2000)
   PUBMED   11256614
REFERENCE   9  (bases 1 to 4411)
  AUTHORS   Hu,R.M., Han,Z.G., Song,H.D., Peng,Y.D., Huang,Q.H., Ren,S.X.,
            Gu,Y.J., Huang,C.H., Li,Y.B., Jiang,C.L., Fu,G., Zhang,Q.H.,
            Gu,B.W., Dai,M., Mao,Y.F., Gao,G.F., Rong,R., Ye,M., Zhou,J.,
            Xu,S.H., Gu,J., Shi,J.X., Jin,W.R., Zhang,C.K., Wu,T.M.,
            Huang,G.Y., Chen,Z., Chen,M.D. and Chen,J.L.
  TITLE     Gene expression profiling in the human
            hypothalamus-pituitary-adrenal axis and full-length cDNA cloning
  JOURNAL   Proc Natl Acad Sci U S A 97 (17), 9543-9548 (2000)
   PUBMED   10931946
REFERENCE   10 (bases 1 to 4411)
  AUTHORS   Chen,J.J. and London,I.M.
  TITLE     Regulation of protein synthesis by heme-regulated eIF-2 alpha
            kinase
  JOURNAL   Trends Biochem Sci 20 (3), 105-108 (1995)
   PUBMED   7709427
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DC341983.1, BC006524.2 and
            AC005995.3.
            
            On Nov 22, 2018 this sequence version replaced NM_014413.3.
            
            Summary: The protein encoded by this gene acts at the level of
            translation initiation to downregulate protein synthesis in
            response to stress. The encoded protein is a kinase that can be
            inactivated by hemin. Two transcript variants encoding different
            isoforms have been found for this gene. [provided by RefSeq, Aug
            2008].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (a).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data because no single transcript was available
            for the full length of the gene. The extent of this transcript is
            supported by transcript alignments.
            
            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 :: SRR1803613.3633.1,
                                           SRR1803615.269101.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000199389.11/ ENSP00000199389.6
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-14                DC341983.1         55-68
            15-2830             BC006524.2         1-2816
            2831-4411           AC005995.3         19726-21306
FEATURES             Location/Qualifiers
     source          1..4411
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7p22.1"
     gene            1..4411
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /note="eukaryotic translation initiation factor 2 alpha
                     kinase 1"
                     /db_xref="GeneID:27102"
                     /db_xref="HGNC:HGNC:24921"
                     /db_xref="MIM:613635"
     exon            1..210
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     CDS             93..1985
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /EC_number="2.7.11.1"
                     /note="isoform a is encoded by transcript variant 1; heme
                     sensitive initiation factor 2a kinase; heme regulated
                     initiation factor 2 alpha kinase; heme-regulated
                     inhibitor; heme-regulated repressor; heme-controlled
                     repressor; hemin-sensitive initiation factor 2-alpha
                     kinase; heme-regulated eukaryotic initiation factor
                     eIF-2-alpha kinase; hemin-controlled repressor"
                     /codon_start=1
                     /product="eukaryotic translation initiation factor 2-alpha
                     kinase 1 isoform a"
                     /protein_id="NP_055228.2"
                     /db_xref="CCDS:CCDS5345.1"
                     /db_xref="GeneID:27102"
                     /db_xref="HGNC:HGNC:24921"
                     /db_xref="MIM:613635"
                     /translation="MQGGNSGVRKREEEGDGAGAVAAPPAIDFPAEGPDPEYDESDVP
                     AEIQVLKEPLQQPTFPFAVANQLLLVSLLEHLSHVHEPNPLRSRQVFKLLCQTFIKMG
                     LLSSFTCSDEFSSLRLHHNRAITHLMRSAKERVRQDPCEDISRIQKIRSREVALEAQT
                     SRYLNEFEELAILGKGGYGRVYKVRNKLDGQYYAIKKILIKGATKTVCMKVLREVKVL
                     AGLQHPNIVGYHTAWIEHVHVIQPRADRAAIELPSLEVLSDQEEDREQCGVKNDESSS
                     SSIIFAEPTPEKEKRFGESDTENQNNKSVKYTTNLVIRESGELESTLELQENGLAGLS
                     ASSIVEQQLPLRRNSHLEESFTSTEESSEENVNFLGQTEAQYHLMLHIQMQLCELSLW
                     DWIVERNKRGREYVDESACPYVMANVATKIFQELVEGVFYIHNMGIVHRDLKPRNIFL
                     HGPDQQVKIGDFGLACTDILQKNTDWTNRNGKRTPTHTSRVGTCLYASPEQLEGSEYD
                     AKSDMYSLGVVLLELFQPFGTEMERAEVLTGLRTGQLPESLRKRCPVQAKYIQHLTRR
                     NSSQRPSAIQLLQSELFQNSGNVNLTLQMKIIEQEKEIAELKKQLNLLSQDKGVRDDG
                     KDGGVG"
     exon            211..369
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            370..503
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            504..541
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            542..641
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            642..722
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            723..822
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            823..883
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            884..1211
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            1212..1323
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            1324..1424
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            1425..1539
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            1540..1622
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            1623..1856
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     exon            1857..4411
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2808..2813
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /note="hexamer: AATAAA"
     polyA_site      2823
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /note="major polyA site"
     polyA_site      2830
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /note="major polyA site"
     regulatory      2866..2871
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /note="hexamer: AATAAA"
     polyA_site      2887
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /note="major polyA site"
     regulatory      4382..4387
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
                     /note="hexamer: AATAAA"
     polyA_site      4411
                     /gene="EIF2AK1"
                     /gene_synonym="HCR; hHRI; HRI; LEMSPAD"
ORIGIN      
        1 acttccgggt cggacggcgc tagctgcagc atcggagtgt ggcagtgctg ggctggccgg
       61 cgggctgggc tgcggcccgc gcgcggccgg cgatgcaggg gggcaactcc ggggtccgca
      121 agcgcgaaga ggagggcgac ggggctgggg ctgtggctgc gccgccggcc atcgactttc
      181 ccgccgaggg cccggacccc gaatatgacg aatctgatgt tccagcagaa atccaggtgt
      241 taaaagaacc cctacaacag ccaaccttcc cttttgcagt tgcaaaccaa ctcttgctgg
      301 tttctttgct ggagcacttg agccacgtgc atgaaccaaa cccacttcgt tcaagacagg
      361 tgtttaagct actttgccag acgtttatca aaatggggct gctgtcttct ttcacttgta
      421 gtgacgagtt tagctcattg agactacatc acaacagagc tattactcac ttaatgaggt
      481 ctgctaaaga gagagttcgt caggatcctt gtgaggatat ttctcgtatc cagaaaatca
      541 gatcaaggga agtagccttg gaagcacaaa cttcacgtta cttaaatgaa tttgaagaac
      601 ttgccatctt aggaaaaggt ggatacggaa gagtatacaa ggtcaggaat aaattagatg
      661 gtcagtatta tgcaataaaa aaaatcctga ttaagggtgc aactaaaaca gtttgcatga
      721 aggtcctacg ggaagtgaag gtgctggcag gtcttcagca ccccaatatt gttggctatc
      781 acaccgcgtg gatagaacat gttcatgtga ttcagccacg agcagacaga gctgccattg
      841 agttgccatc tctggaagtg ctctccgacc aggaagagga cagagagcaa tgtggtgtta
      901 aaaatgatga aagtagcagc tcatccatta tctttgctga gcccacccca gaaaaagaaa
      961 aacgctttgg agaatctgac actgaaaatc agaataacaa gtcggtgaag tacaccacca
     1021 atttagtcat aagagaatct ggtgaacttg agtcgaccct ggagctccag gaaaatggct
     1081 tggctggttt gtctgccagt tcaattgtgg aacagcagct gccactcagg cgtaattccc
     1141 acctagagga gagtttcaca tccaccgaag aatcttccga agaaaatgtc aactttttgg
     1201 gtcagacaga ggcacagtac cacctgatgc tgcacatcca gatgcagctg tgtgagctct
     1261 cgctgtggga ttggatagtc gagagaaaca agcggggccg ggagtatgtg gacgagtctg
     1321 cctgtcctta tgttatggcc aatgttgcaa caaaaatttt tcaagaattg gtagaaggtg
     1381 tgttttacat acataacatg ggaattgtgc accgagatct gaagccaaga aatatttttc
     1441 ttcatggccc tgatcagcaa gtaaaaatag gagactttgg tctggcctgc acagacatcc
     1501 tacagaagaa cacagactgg accaacagaa acgggaagag aacaccaaca catacgtcca
     1561 gagtgggtac ttgtctgtac gcttcacccg aacagttgga aggatctgag tatgatgcca
     1621 agtcagatat gtacagcttg ggtgtggtcc tgctagagct ctttcagccg tttggaacag
     1681 aaatggagcg agcagaagtt ctaacaggtt taagaactgg tcagttgccg gaatccctcc
     1741 gtaaaaggtg tccagtgcaa gccaagtata tccagcactt aacgagaagg aactcatcgc
     1801 agagaccatc tgccattcag ctgctgcaga gtgaactttt ccaaaattct ggaaatgtta
     1861 acctcaccct acagatgaag ataatagagc aagaaaaaga aattgcagaa ctaaagaagc
     1921 agctaaacct cctttctcaa gacaaagggg tgagggatga cggaaaggat gggggcgtgg
     1981 gatgaaagtg gacttaactt ttaaggtagt taactggaat gtaaattttt aatctttatt
     2041 agggtatagt tggtacaatg cttcgttgta tttagtaagc ctttacaaga cttgttaaag
     2101 atgtcagagt gccccaagct gccgttcctt cccttcctgc cccacaagct ccttttcctg
     2161 aatttcctac ctaaatatta accatatgcc tagtctctga aactaaaaac ttggacctca
     2221 tcctcaatta ttttctcctt tcaactctgt tgaccctctg tctggtcttc ctctagaagg
     2281 taccgcagaa attgatgtgt gctccctgcc ctcgtcactg cccaagcccg ggcctgcaca
     2341 tactcactgg actgttccag ttttgacagc tgccagtctt cctgcccctt tcacactgca
     2401 gctgaagttc attacctgaa ggacgcctca tcatttcatt ccttggctcc aaaccttctg
     2461 ctgcctctaa gataaaagct caacttctta acagtgtaca gtgtgcaact tccaaccttt
     2521 ttatctgttc tctccacctt cagtttagcg tcattccaaa accacaccct tgcaaagctt
     2581 tgtactccgc accccagatg atctccaggc agctcagatc tctttcctgc ctttgccctg
     2641 cactgttccc cggtacttcc tcctttattg tagcactcag ctccccagcc aatctgtaca
     2701 tccctcagag gcagcgatct gatgaattgg tttttgaatc ccagaaaggg tctgccatgg
     2761 agttggcagt catcacggta gatggcgtat gattttgctg aattttaaat aaaatgaaaa
     2821 ccataaatta catgatgctt ttattgacac ttgacaactg gcctaaataa aaagactctg
     2881 actctaatac aagtcccctt actgataata ggcatgaaag agcaccattc ttaaaatcta
     2941 aaccctttaa aatcagttac ggcaattcac ttaaggagct tgagggccgt gttaaaagga
     3001 gccaggtttt cacaagacct catccacctc tgcacattgg ctggcactgt cacactgcag
     3061 cctccgatct gctggagtac agaccacagc accacgtctg ctacggtgag ttcattccca
     3121 gcgagccaag ggctcttccc aagagcagag ttcatggagc ggaaaacagc ggctttttct
     3181 ttactgcttc cctcttttaa ctgaaaaatc gcaatatcta cccagctatc tataagggtt
     3241 gcgttgacag cattatgctt ctggccaaac agagagaaca agaaacgtgc aatgttccct
     3301 tcgccttcga tggggcacat cgtctggatg ctgaatttca tctgcgtctt cggcactgaa
     3361 aagaaaaaac acgccaggta gcatcaccag agcagccctg agggaagtac tcgcacagtg
     3421 gggaagggga cagtcaccaa acaccacaga ctgatgacat gggaaagggt gttttcaaga
     3481 agaacatcac attttcagtc tgtctctaag atgcttacta ctgaaaaggg tttaagtgca
     3541 aactatgtta aaaaagtaac caaagagtca ttcctggtat ttgattatga cacttctgaa
     3601 gctagaaggg acctcagacc acctgctcca atccctgctg cctaaggttt tgggggctga
     3661 gggctggaaa cccaggagct gcatctccca ggctcttggc ctcataatcg ccttctgtga
     3721 gactgagggc aattaagata tgaatgacat gaactcgctt atctccatat caacataaac
     3781 cagaagaggc atacatctgt gggatagtca atacataaca tcctatcttt atatggccat
     3841 atgagaagat aacttcagtg tccctatgat ggtaagttct tgaatgtgag ggcaagatgg
     3901 ctgtgatagc catgactccc cgctttgcct ggttggacag aacccccttc cccaaatgct
     3961 cacagtcccc cccttgagct gtgtctcact cagagaccct aaattttgca gacgaacaag
     4021 ggcatctttg cgttgcttca tctctgctcc tcctctagaa ctatcccaca ggctttctag
     4081 acttagaata tctgacctga tgcaaatcgc tatgtggcca gtatgccaca gaatgtccta
     4141 aacccttgct gcctcttatc aaaaccatgt tgcacatctc atcatatagt acagctaacc
     4201 cttgaacagt gggggggtta gggacactga cccccgactg ctgtgcagtc gaaaatccac
     4261 ataaaacttc tgactccttc aaaacttaag cactaatagc ctactattca tgggaagcct
     4321 tacccatcac agttgattaa cacgttttgt atggtctgta tattatatgc tatattctta
     4381 caataaactt gagaaaatgt taagaaaata a
//
