LOCUS       NM_004836               4536 bp    mRNA    linear   PRI 08-DEC-2024
DEFINITION  Homo sapiens eukaryotic translation initiation factor 2 alpha
            kinase 3 (EIF2AK3), transcript variant 1, mRNA.
ACCESSION   NM_004836
VERSION     NM_004836.7
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 4536)
  AUTHORS   Mafi,S., Dehghani,M., Khalvati,B., Abidi,H., Ghorbani,M.,
            Jalali,P., Whichelo,R., Salehi,Z., Markowska,A., Reyes,A.,
            Pecic,S., Los,M.J., Ghavami,S. and Nikseresht,M.
  TITLE     Targeting PERK and GRP78 in colorectal cancer: Genetic insights and
            novel therapeutic approaches
  JOURNAL   Eur J Pharmacol 982, 176899 (2024)
   PUBMED   39153651
  REMARK    GeneRIF: Targeting PERK and GRP78 in colorectal cancer: Genetic
            insights and novel therapeutic approaches.
REFERENCE   2  (bases 1 to 4536)
  AUTHORS   Brar,K.K., Hughes,D.T., Morris,J.L., Subramanian,K., Krishna,S.,
            Gao,F., Rieder,L.S., Uhrig,S., Freeman,J., Smith,H.L.,
            Jukes-Jones,R., Avezov,E., Nunnari,J., Prudent,J., Butcher,A.J. and
            Mallucci,G.R.
  TITLE     PERK-ATAD3A interaction provides a subcellular safe haven for
            protein synthesis during ER stress
  JOURNAL   Science 385 (6712), eadp7114 (2024)
   PUBMED   39116259
  REMARK    GeneRIF: PERK-ATAD3A interaction provides a subcellular safe haven
            for protein synthesis during ER stress.
REFERENCE   3  (bases 1 to 4536)
  AUTHORS   Akay-Espinoza,C., Newton,S.E.B., Dombroski,B.A., Kallianpur,A.,
            Bharti,A., Franklin,D.R., Schellenberg,G.D., Heaton,R.K., Grant,I.,
            Ellis,R.J., Letendre,S.L. and Jordan-Sciutto,K.L.
  TITLE     Genetic Variations in EIF2AK3 are Associated with Neurocognitive
            Impairment in People Living with HIV
  JOURNAL   J Neuroimmune Pharmacol 19 (1), 25 (2024)
   PUBMED   38789639
  REMARK    GeneRIF: Genetic Variations in EIF2AK3 are Associated with
            Neurocognitive Impairment in People Living with HIV.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4536)
  AUTHORS   Liu,F., Liu,Z., Cheng,W., Zhao,Q., Zhang,X., Zhang,H., Yu,M.,
            Xu,H., Gao,Y., Jiang,Q., Shi,G., Wang,L., Gu,S., Wang,J., Cao,N.
            and Chen,Z.
  TITLE     The PERK Branch of the Unfolded Protein Response Safeguards Protein
            Homeostasis and Mesendoderm Specification of Human Pluripotent Stem
            Cells
  JOURNAL   Adv Sci (Weinh) 10 (35), e2303799 (2023)
   PUBMED   37890465
  REMARK    GeneRIF: The PERK Branch of the Unfolded Protein Response
            Safeguards Protein Homeostasis and Mesendoderm Specification of
            Human Pluripotent Stem Cells.
REFERENCE   5  (bases 1 to 4536)
  AUTHORS   Majumder,S., Chattopadhyay,A., Wright,J.M., Guan,P., Buja,L.M.,
            Kwartler,C.S. and Milewicz,D.M.
  TITLE     Pericentrin deficiency in smooth muscle cells augments
            atherosclerosis through HSF1-driven cholesterol biosynthesis and
            PERK activation
  JOURNAL   JCI Insight 8 (21), e173247 (2023)
   PUBMED   37937642
  REMARK    GeneRIF: Pericentrin deficiency in smooth muscle cells augments
            atherosclerosis through HSF1-driven cholesterol biosynthesis and
            PERK activation.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 4536)
  AUTHORS   Shi,Y., An,J., Liang,J., Hayes,S.E., Sandusky,G.E., Stramm,L.E. and
            Yang,N.N.
  TITLE     Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and
            co-localization with somatostatin in islet delta cells
  JOURNAL   J Biol Chem 274 (9), 5723-5730 (1999)
   PUBMED   10026192
REFERENCE   7  (bases 1 to 4536)
  AUTHORS   Shi,Y., Vattem,K.M., Sood,R., An,J., Liang,J., Stramm,L. and
            Wek,R.C.
  TITLE     Identification and characterization of pancreatic eukaryotic
            initiation factor 2 alpha-subunit kinase, PEK, involved in
            translational control
  JOURNAL   Mol Cell Biol 18 (12), 7499-7509 (1998)
   PUBMED   9819435
REFERENCE   8  (bases 1 to 4536)
  AUTHORS   Dever,T.E., Chen,J.J., Barber,G.N., Cigan,A.M., Feng,L.,
            Donahue,T.F., London,I.M., Katze,M.G. and Hinnebusch,A.G.
  TITLE     Mammalian eukaryotic initiation factor 2 alpha kinases functionally
            substitute for GCN2 protein kinase in the GCN4 translational
            control mechanism of yeast
  JOURNAL   Proc Natl Acad Sci U S A 90 (10), 4616-4620 (1993)
   PUBMED   8099443
REFERENCE   9  (bases 1 to 4536)
  AUTHORS   De Leon,D.D. and Pinney,S.E.
  TITLE     Permanent Neonatal Diabetes Mellitus
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301620
REFERENCE   10 (bases 1 to 4536)
  AUTHORS   Mellor,H. and Proud,C.G.
  TITLE     A synthetic peptide substrate for initiation factor-2 kinases
  JOURNAL   Biochem Biophys Res Commun 178 (2), 430-437 (1991)
   PUBMED   1677563
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC062029.7, AK128659.1,
            AC104134.4 and CB162654.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_004836.6.
            
            Summary: The protein encoded by this gene phosphorylates the alpha
            subunit of eukaryotic translation-initiation factor 2, leading to
            its inactivation, and thus to a rapid reduction of translational
            initiation and repression of global protein synthesis. This protein
            is thought to modulate mitochondrial function. It is a type I
            membrane protein located in the endoplasmic reticulum (ER), where
            it is induced by ER stress caused by malfolded proteins. Mutations
            in this gene are associated with Wolcott-Rallison syndrome.
            [provided by RefSeq, Sep 2015].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on 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 :: AF193339.1, AF110146.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000303236.9/ ENSP00000307235.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-381               AC062029.7         28944-29324         c
            382-686             AK128659.1         247-551
            687-687             AC104134.4         105592-105592       c
            688-2299            AK128659.1         553-2164
            2300-2300           AC104134.4         85360-85360         c
            2301-4534           AK128659.1         2166-4399
            4535-4536           CB162654.1         571-572
FEATURES             Location/Qualifiers
     source          1..4536
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p11.2"
     gene            1..4536
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /note="eukaryotic translation initiation factor 2 alpha
                     kinase 3"
                     /db_xref="GeneID:9451"
                     /db_xref="HGNC:HGNC:3255"
                     /db_xref="MIM:604032"
     exon            1..498
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     CDS             191..3541
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /EC_number="2.7.11.1"
                     /EC_number="2.7.10.2"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; pancreatic EIF2-alpha kinase; PRKR-like
                     endoplasmic reticulum kinase; pancreatic eIF-2alpha
                     kinase; PKR-like ER kinase; protein tyrosine kinase
                     EIF2AK3"
                     /codon_start=1
                     /product="eukaryotic translation initiation factor 2-alpha
                     kinase 3 isoform 1 precursor"
                     /protein_id="NP_004827.4"
                     /db_xref="CCDS:CCDS33241.1"
                     /db_xref="GeneID:9451"
                     /db_xref="HGNC:HGNC:3255"
                     /db_xref="MIM:604032"
                     /translation="MERAISPGLLVRALLLLLLLLGLAARTVAAGRARGLPAPTAEAA
                     FGLGAAAAPTSATRVPAAGAVAAAEVTVEDAEALPAAAGEQEPRGPEPDDETELRPRG
                     RSLVIISTLDGRIAALDPENHGKKQWDLDVGSGSLVSSSLSKPEVFGNKMIIPSLDGA
                     LFQWDQDRESMETVPFTVESLLESSYKFGDDVVLVGGKSLTTYGLSAYSGKVRYICSA
                     LGCRQWDSDEMEQEEDILLLQRTQKTVRAVGPRSGNEKWNFSVGHFELRYIPDMETRA
                     GFIESTFKPNENTEESKIISDVEEQEAAIMDIVIKVSVADWKVMAFSKKGGHLEWEYQ
                     FCTPIASAWLLKDGKVIPISLFDDTSYTSNDDVLEDEEDIVEAARGATENSVYLGMYR
                     GQLYLQSSVRISEKFPSSPKALESVTNENAIIPLPTIKWKPLIHSPSRTPVLVGSDEF
                     DKCLSNDKFSHEEYSNGALSILQYPYDNGYYLPYYKRERNKRSTQITVRFLDNPHYNK
                     NIRKKDPVLLLHWWKEIVATILFCIIATTFIVRRLFHPHPHRQRKESETQCQTENKYD
                     SVSGEANDSSWNDIKNSGYISRYLTDFEPIQCLGRGGFGVVFEAKNKVDDCNYAIKRI
                     RLPNRELAREKVMREVKALAKLEHPGIVRYFNAWLEAPPEKWQEKMDEIWLKDESTDW
                     PLSSPSPMDAPSVKIRRMDPFATKEHIEIIAPSPQRSRSFSVGISCDQTSSSESQFSP
                     LEFSGMDHEDISESVDAAYNLQDSCLTDCDVEDGTMDGNDEGHSFELCPSEASPYVRS
                     RERTSSSIVFEDSGCDNASSKEEPKTNRLHIGNHCANKLTAFKPTSSKSSSEATLSIS
                     PPRPTTLSLDLTKNTTEKLQPSSPKVYLYIQMQLCRKENLKDWMNGRCTIEERERSVC
                     LHIFLQIAEAVEFLHSKGLMHRDLKPSNIFFTMDDVVKVGDFGLVTAMDQDEEEQTVL
                     TPMPAYARHTGQVGTKLYMSPEQIHGNSYSHKVDIFSLGLILFELLYPFSTQMERVRT
                     LTDVRNLKFPPLFTQKYPCEYVMVQDMLSPSPMERPEAINIIENAVFEDLDFPGKTVL
                     RQRSRSLSSSGTKHSRQSNNSHSPLPSN"
     exon            499..628
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            629..823
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            824..957
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            958..1192
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1193..1355
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1356..1496
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1497..1619
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1620..1840
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1841..1953
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1954..2076
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2077..2226
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2227..3007
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            3008..3175
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            3176..3277
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            3278..3340
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     exon            3341..4536
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4515..4520
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /note="hexamer: AATAAA"
     polyA_site      4536
                     /gene="EIF2AK3"
                     /gene_synonym="PEK; PERK; WRS"
                     /note="major polyA site"
ORIGIN      
        1 aggctgtcac tcaggtggca gcggcagagg ccgggctgag acgtggccag gggaacacgg
       61 ctggctgtcc aggccgtcgg ggcggcagta gggtccctag cacgtccttg ccttcttggg
      121 agctccaagc ggcgggagag gcaggcgtca gtggctgcgc ctccatgcct gcgcgcgggg
      181 cgggacgctg atggagcgcg ccatcagccc ggggctgctg gtacgggcgc tgctgctgct
      241 gctgctgctg ctggggctcg cggcaaggac ggtggccgcg gggcgcgccc gtggcctccc
      301 agcgccgacg gcggaggcgg cgttcggcct cggggcggcc gctgctccca cctcagcgac
      361 gcgagtaccg gcggcgggcg ccgtggctgc ggccgaggtg actgtggagg acgctgaggc
      421 gctgccggca gccgcgggag agcaggagcc tcggggtccg gaaccagacg atgagacaga
      481 gttgcgaccg cgcggcaggt cattagtaat tatcagcact ttagatggga gaattgctgc
      541 cttggatcct gaaaatcatg gtaaaaagca gtgggatttg gatgtgggat ccggttcctt
      601 ggtgtcatcc agccttagca aaccagaggt atttgggaat aagatgatca ttccttccct
      661 ggatggagcc ctcttccagt gggaccaaga ccgtgaaagc atggaaacag ttcctttcac
      721 agttgaatca cttcttgaat cttcttataa atttggagat gatgttgttt tggttggagg
      781 aaaatctctg actacatatg gactcagtgc atatagtgga aaggtgaggt atatctgttc
      841 agctctgggt tgtcgccaat gggatagtga cgaaatggaa caagaggaag acatcctgct
      901 tctacagcgt acccaaaaaa ctgttagagc tgtcggacct cgcagtggca atgagaagtg
      961 gaatttcagt gttggccact ttgaacttcg gtatattcca gacatggaaa cgagagccgg
     1021 atttattgaa agcaccttta agcccaatga gaacacagaa gagtctaaaa ttatttcaga
     1081 tgtggaagaa caggaagctg ccataatgga catagtgata aaggtttcgg ttgctgactg
     1141 gaaagttatg gcattcagta agaagggagg acatctggaa tgggagtacc agttttgtac
     1201 tccaattgca tctgcctggt tacttaagga tgggaaagtc attcccatca gtctttttga
     1261 tgatacaagt tatacatcta atgatgatgt tttagaagat gaagaagaca ttgtagaagc
     1321 tgccagagga gccacagaaa acagtgttta cttgggaatg tatagaggcc agctgtatct
     1381 gcagtcatca gtcagaattt cagaaaagtt tccttcaagt cccaaggctt tggaatctgt
     1441 cactaatgaa aacgcaatta ttcctttacc aacaatcaaa tggaaaccct taattcattc
     1501 tccttccaga actcctgtct tggtaggatc tgatgaattt gacaaatgtc tcagtaatga
     1561 taagttttct catgaagaat atagtaatgg tgcactttca atcttgcagt atccatatga
     1621 taatggttat tatctaccat actacaagag ggagaggaac aaacgaagca cacagattac
     1681 agtcagattc ctcgacaacc cacattacaa caagaatatc cgcaaaaagg atcctgttct
     1741 tcttttacac tggtggaaag aaatagttgc aacgattttg ttttgtatca tagcaacaac
     1801 gtttattgtg cgcaggcttt tccatcctca tcctcacagg caaaggaagg agtctgaaac
     1861 tcagtgtcaa actgaaaata aatatgattc tgtaagtggt gaagccaatg acagtagctg
     1921 gaatgacata aaaaactctg gatatatatc acgatatcta actgattttg agccaattca
     1981 atgcctggga cgtggtggct ttggagttgt ttttgaagct aaaaacaaag tagatgactg
     2041 caattatgct atcaagagga tccgtctccc caatagggaa ttggctcggg aaaaggtaat
     2101 gcgagaagtt aaagccttag ccaagcttga acacccgggc attgttagat atttcaatgc
     2161 ctggctcgaa gcaccaccag agaagtggca agaaaagatg gatgaaattt ggctgaaaga
     2221 tgaaagcaca gactggccac tcagctctcc tagcccaatg gatgcaccat cagttaaaat
     2281 acgcagaatg gatcctttcg ctacaaaaga acatattgaa atcatagctc cttcaccaca
     2341 aagaagcagg tctttttcag tagggatttc ctgtgaccag acaagttcat ctgagagcca
     2401 gttctcacca ctggaattct caggaatgga ccatgaggac atcagtgagt cagtggatgc
     2461 agcatacaac ctccaggaca gttgccttac agactgtgat gtggaagatg ggactatgga
     2521 tggcaatgat gaggggcact cctttgaact ttgtccttct gaagcttctc cttatgtaag
     2581 gtcaagggag agaacctcct cttcaatagt atttgaagat tctggctgtg ataatgcttc
     2641 cagtaaagaa gagccgaaaa ctaatcgatt gcatattggc aaccattgtg ctaataaact
     2701 aactgctttc aagcccacca gtagcaaatc ttcttctgaa gctacattgt ctatttctcc
     2761 tccaagacca accactttaa gtttagatct cactaaaaac accacagaaa aactccagcc
     2821 cagttcacca aaggtgtatc tttacattca aatgcagctg tgcagaaaag aaaacctcaa
     2881 agactggatg aatggacgat gtaccataga ggagagagag aggagcgtgt gtctgcacat
     2941 cttcctgcag atcgcagagg cagtggagtt tcttcacagt aaaggactga tgcacaggga
     3001 cctcaagcca tccaacatat tctttacaat ggatgatgtg gtcaaggttg gagactttgg
     3061 gttagtgact gcaatggacc aggatgagga agagcagacg gttctgaccc caatgccagc
     3121 ttatgccaga cacacaggac aagtagggac caaactgtat atgagcccag agcagattca
     3181 tggaaacagc tattctcata aagtggacat cttttcttta ggcctgattc tatttgaatt
     3241 gctgtatcca ttcagcactc agatggagag agtcaggacc ttaactgatg taagaaatct
     3301 caaatttcca ccattattta ctcagaaata tccttgtgag tacgtgatgg ttcaagacat
     3361 gctctctcca tcccccatgg aacgacctga agctataaac atcattgaaa atgctgtatt
     3421 tgaggacttg gactttccag gaaaaacagt gctcagacag aggtctcgct ccttgagttc
     3481 atcgggaaca aaacattcaa gacagtccaa caactcccat agccctttgc caagcaatta
     3541 gccttaagtt gtgctagcaa ccctaatagg tgatgcagat aatagcctac ttcttagaat
     3601 atgcctgtcc aaaattgcag acttgaaaag tttgttcttc gctcaatttt tttgtggact
     3661 acttttttta tatcaaattt aagctggatt tgggggcata acctaatttg agccaactcc
     3721 tgagttttgc tatacttaag gaaagggcta tctttgttct ttgttagtct cttgaaactg
     3781 gctgctggcc aagctttata gccctcacca tttgcctaag gaggtagcag caatccctaa
     3841 tatatatata tagtgagaac taaaatggat atatttttat aatgcagaag aaggaaagtc
     3901 cccctgtgtg gtaactgtat tgttctagaa atatgctttc tagagatatg atgattttga
     3961 aactgatttc tagaaaaagc tgactccatt tttgtccctg gcgggtaaat taggaatctg
     4021 cactattttg gaggacaagt agcacaaact gtataacggt ttatgtccgt agttttatag
     4081 tcctatttgt agcattcaat agctttattc cttagatggt tctagggtgg gtttacagct
     4141 ttttgtactt ttacctccaa taaagggaaa atgaagcttt ttatgtaaat tggttgaaag
     4201 gtctagtttt gggaggaaaa aagccgtagt aagaaatgga tcatatatat tacaactaac
     4261 ttcttcaact atggactttt taagcctaat gaaatcttaa gtgtcttata tgtaatcctg
     4321 taggttggta cttcccccaa actgattata ggtaacagtt taatcatctc acttgctaac
     4381 atgtttttat ttttcactgt aaatatgttt atgttttatt tataaaaatt ctgaaatcaa
     4441 tccatttggg ttggtggtgt acagaacaca cttaagtgtg ttaacttgtg acttctttca
     4501 agtctaaatg atttaataaa acttttttta aattaa
//
