LOCUS       NM_001135651            9975 bp    mRNA    linear   PRI 01-AUG-2024
DEFINITION  Homo sapiens eukaryotic translation initiation factor 2 alpha
            kinase 2 (EIF2AK2), transcript variant 2, mRNA.
ACCESSION   NM_001135651
VERSION     NM_001135651.3
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 9975)
  AUTHORS   Gong,Y., Xiao,X.Y., Hu,Y.S., Xie,Y.W. and Wu,Z.H.
  TITLE     [Research Advances in the Association Between Alzheimer's Disease
            and Double-Stranded RNA-Dependent Protein Kinase]
  JOURNAL   Zhongguo Yi Xue Ke Xue Yuan Xue Bao 46 (3), 425-434 (2024)
   PUBMED   38953267
  REMARK    GeneRIF: [Research Advances in the Association Between Alzheimer's
            Disease and Double-Stranded RNA-Dependent Protein Kinase].
            Review article
REFERENCE   2  (bases 1 to 9975)
  AUTHORS   Hotani,T., Nakagawa,K., Tsukamoto,T., Mizuguchi,H. and Sakurai,F.
  TITLE     Involvement of Protein Kinase R in Double-Stranded RNA-Induced
            Proteasomal Degradation of Hypoxia Inducible Factor-1alpha
  JOURNAL   Inflammation 46 (6), 2332-2342 (2023)
   PUBMED   37615898
  REMARK    GeneRIF: Involvement of Protein Kinase R in Double-Stranded
            RNA-Induced Proteasomal Degradation of Hypoxia Inducible
            Factor-1alpha.
REFERENCE   3  (bases 1 to 9975)
  AUTHORS   Kolac,U.K., Donmez Yalcin,G., Karayel,R. and Yalcin,A.
  TITLE     The role of protein kinase R in placental inflammation, mtUPR and
            apoptosis
  JOURNAL   Placenta 139, 200-211 (2023)
   PUBMED   37463546
  REMARK    GeneRIF: The role of protein kinase R in placental inflammation,
            mtUPR and apoptosis.
REFERENCE   4  (bases 1 to 9975)
  AUTHORS   Kim,H.J., Han,C.W., Jeong,M.S. and Jang,S.B.
  TITLE     Structural study of novel vaccinia virus E3L and dsRNA-dependent
            protein kinase complex
  JOURNAL   Biochem Biophys Res Commun 665, 1-9 (2023)
   PUBMED   37146409
  REMARK    GeneRIF: Structural study of novel vaccinia virus E3L and
            dsRNA-dependent protein kinase complex.
REFERENCE   5  (bases 1 to 9975)
  AUTHORS   Li,Q., Zhao,Y.H., Xu,C., Liang,Y.L., Zhao,Y., He,Q.M., Li,J.Y.,
            Chen,K.L., Qiao,H., Liu,N., Ma,J., Chen,L. and Li,Y.Q.
  TITLE     Chemotherapy-Induced Senescence Reprogramming Promotes
            Nasopharyngeal Carcinoma Metastasis by circRNA-Mediated PKR
            Activation
  JOURNAL   Adv Sci (Weinh) 10 (8), e2205668 (2023)
   PUBMED   36683218
  REMARK    GeneRIF: Chemotherapy-Induced Senescence Reprogramming Promotes
            Nasopharyngeal Carcinoma Metastasis by circRNA-Mediated PKR
            Activation.
REFERENCE   6  (bases 1 to 9975)
  AUTHORS   Feng,G.S., Chong,K., Kumar,A. and Williams,B.R.
  TITLE     Identification of double-stranded RNA-binding domains in the
            interferon-induced double-stranded RNA-activated p68 kinase
  JOURNAL   Proc Natl Acad Sci U S A 89 (12), 5447-5451 (1992)
   PUBMED   1351683
REFERENCE   7  (bases 1 to 9975)
  AUTHORS   McCormack,S.J., Thomis,D.C. and Samuel,C.E.
  TITLE     Mechanism of interferon action: identification of a RNA binding
            domain within the N-terminal region of the human RNA-dependent
            P1/eIF-2 alpha protein kinase
  JOURNAL   Virology 188 (1), 47-56 (1992)
   PUBMED   1373554
REFERENCE   8  (bases 1 to 9975)
  AUTHORS   Thomis,D.C., Doohan,J.P. and Samuel,C.E.
  TITLE     Mechanism of interferon action: cDNA structure, expression, and
            regulation of the interferon-induced, RNA-dependent P1/eIF-2 alpha
            protein kinase from human cells
  JOURNAL   Virology 188 (1), 33-46 (1992)
   PUBMED   1373553
REFERENCE   9  (bases 1 to 9975)
  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
REFERENCE   10 (bases 1 to 9975)
  AUTHORS   Meurs,E., Chong,K., Galabru,J., Thomas,N.S., Kerr,I.M.,
            Williams,B.R. and Hovanessian,A.G.
  TITLE     Molecular cloning and characterization of the human double-stranded
            RNA-activated protein kinase induced by interferon
  JOURNAL   Cell 62 (2), 379-390 (1990)
   PUBMED   1695551
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC040851.1, AC007899.3 and
            BU687340.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_001135651.2.
            
            Summary: The protein encoded by this gene is a serine/threonine
            protein kinase that is activated by autophosphorylation after
            binding to dsRNA. The activated form of the encoded protein can
            phosphorylate translation initiation factor EIF2S1, which in turn
            inhibits protein synthesis. This protein is also activated by
            manganese ions and heparin. The encoded protein plays an important
            role in the innate immune response against multiple DNA and RNA
            viruses. [provided by RefSeq, Jul 2021].
            
            Transcript Variant: This variant (2) uses a different splice site
            in the 5' UTR, compared to variant 1. Variants 1 and 2 both encode
            the same protein (isoform a).
            
            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 :: SRR14038195.433394.1,
                                           SRR11853564.15221.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            coronavirus related    :: involved in immune response or antiviral
                                      activity
            MANE Ensembl match     :: ENST00000233057.9/ ENSP00000233057.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1786              BC040851.1         68-1853
            1787-1789           AC007899.3         83729-83731
            1790-3449           AC007899.3         83810-85469
            3450-4047           BU687340.1         14-611              c
            4048-9975           AC007899.3         86068-91995
FEATURES             Location/Qualifiers
     source          1..9975
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p22.2"
     gene            1..9975
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /note="eukaryotic translation initiation factor 2 alpha
                     kinase 2"
                     /db_xref="GeneID:5610"
                     /db_xref="HGNC:HGNC:9437"
                     /db_xref="MIM:176871"
     exon            1..73
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            74..240
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            241..375
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     CDS             257..1912
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /EC_number="2.7.11.1"
                     /EC_number="2.7.10.2"
                     /note="isoform a is encoded by transcript variant 2;
                     protein kinase, interferon-inducible double stranded RNA
                     dependent; interferon-inducible elF2alpha kinase; double
                     stranded RNA activated protein kinase; p68 kinase; eIF-2A
                     protein kinase 2; P1/eIF-2A protein kinase;
                     tyrosine-protein kinase EIF2AK2; protein kinase R; protein
                     phosphatase 1, regulatory subunit 83; protein kinase
                     RNA-regulated"
                     /codon_start=1
                     /product="interferon-induced, double-stranded
                     RNA-activated protein kinase isoform a"
                     /protein_id="NP_001129123.1"
                     /db_xref="CCDS:CCDS1786.1"
                     /db_xref="GeneID:5610"
                     /db_xref="HGNC:HGNC:9437"
                     /db_xref="MIM:176871"
                     /translation="MAGDLSAGFFMEELNTYRQKQGVVLKYQELPNSGPPHDRRFTFQ
                     VIIDGREFPEGEGRSKKEAKNAAAKLAVEILNKEKKAVSPLLLTTTNSSEGLSMGNYI
                     GLINRIAQKKRLTVNYEQCASGVHGPEGFHYKCKMGQKEYSIGTGSTKQEAKQLAAKL
                     AYLQILSEETSVKSDYLSSGSFATTCESQSNSLVTSTLASESSSEGDFSADTSEINSN
                     SDSLNSSSLLMNGLRNNQRKAKRSLAPRFDLPDMKETKYTVDKRFGMDFKEIELIGSG
                     GFGQVFKAKHRIDGKTYVIKRVKYNNEKAEREVKALAKLDHVNIVHYNGCWDGFDYDP
                     ETSDDSLESSDYDPENSKNSSRSKTKCLFIQMEFCDKGTLEQWIEKRRGEKLDKVLAL
                     ELFEQITKGVDYIHSKKLIHRDLKPSNIFLVDTKQVKIGDFGLVTSLKNDGKRTRSKG
                     TLRYMSPEQISSQDYGKEVDLYALGLILAELLHVCDTAFETSKFFTDLRDGIISDIFD
                     KKEKTLLQKLLSKKPEDRPNTSEILRTLTVWKKSPEKNERHTC"
     exon            376..496
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            497..645
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            646..772
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            773..849
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            850..943
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            944..978
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            979..1041
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            1042..1164
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            1165..1323
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            1324..1504
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            1505..1633
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            1634..1735
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            1736..1789
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     exon            1790..9975
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /inference="alignment:Splign:2.1.0"
     regulatory      9951..9956
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /note="hexamer: AATAAA"
     polyA_site      9975
                     /gene="EIF2AK2"
                     /gene_synonym="DYT33; EIF2AK1; LEUDEN; PKR; PPP1R83; PRKR"
                     /note="major polyA site"
ORIGIN      
        1 gaaactgaga accagctctc ccgaagccgc gggtctccgg ccggcggcgg cggcggcggc
       61 ggcggcggcg cagtttctgg agcaaattca gtttgccttc ctggatttgt aaattgtaat
      121 gacctcaaaa ctttagcagt tcttccatct gactcaggtt tgcttctctg gcggtcttca
      181 gaatcaacat ccacacttcc gtgattatct gcgtgcattt tggacaaagc ttccaaccag
      241 gatacgggaa gaagaaatgg ctggtgatct ttcagcaggt ttcttcatgg aggaacttaa
      301 tacataccgt cagaagcagg gagtagtact taaatatcaa gaactgccta attcaggacc
      361 tccacatgat aggaggttta catttcaagt tataatagat ggaagagaat ttccagaagg
      421 tgaaggtaga tcaaagaagg aagcaaaaaa tgccgcagcc aaattagctg ttgagatact
      481 taataaggaa aagaaggcag ttagtccttt attattgaca acaacgaatt cttcagaagg
      541 attatccatg gggaattaca taggccttat caatagaatt gcccagaaga aaagactaac
      601 tgtaaattat gaacagtgtg catcgggggt gcatgggcca gaaggatttc attataaatg
      661 caaaatggga cagaaagaat atagtattgg tacaggttct actaaacagg aagcaaaaca
      721 attggccgct aaacttgcat atcttcagat attatcagaa gaaacctcag tgaaatctga
      781 ctacctgtcc tctggttctt ttgctactac gtgtgagtcc caaagcaact ctttagtgac
      841 cagcacactc gcttctgaat catcatctga aggtgacttc tcagcagata catcagagat
      901 aaattctaac agtgacagtt taaacagttc ttcgttgctt atgaatggtc tcagaaataa
      961 tcaaaggaag gcaaaaagat ctttggcacc cagatttgac cttcctgaca tgaaagaaac
     1021 aaagtatact gtggacaaga ggtttggcat ggattttaaa gaaatagaat taattggctc
     1081 aggtggattt ggccaagttt tcaaagcaaa acacagaatt gacggaaaga cttacgttat
     1141 taaacgtgtt aaatataata acgagaaggc ggagcgtgaa gtaaaagcat tggcaaaact
     1201 tgatcatgta aatattgttc actacaatgg ctgttgggat ggatttgatt atgatcctga
     1261 gaccagtgat gattctcttg agagcagtga ttatgatcct gagaacagca aaaatagttc
     1321 aaggtcaaag actaagtgcc ttttcatcca aatggaattc tgtgataaag ggaccttgga
     1381 acaatggatt gaaaaaagaa gaggcgagaa actagacaaa gttttggctt tggaactctt
     1441 tgaacaaata acaaaagggg tggattatat acattcaaaa aaattaattc atagagatct
     1501 taagccaagt aatatattct tagtagatac aaaacaagta aagattggag actttggact
     1561 tgtaacatct ctgaaaaatg atggaaagcg aacaaggagt aagggaactt tgcgatacat
     1621 gagcccagaa cagatttctt cgcaagacta tggaaaggaa gtggacctct acgctttggg
     1681 gctaattctt gctgaacttc ttcatgtatg tgacactgct tttgaaacat caaagttttt
     1741 cacagaccta cgggatggca tcatctcaga tatatttgat aaaaaagaaa aaactcttct
     1801 acagaaatta ctctcaaaga aacctgagga tcgacctaac acatctgaaa tactaaggac
     1861 cttgactgtg tggaagaaaa gcccagagaa aaatgaacga cacacatgtt agagcccttc
     1921 tgaaaaagta tcctgcttct gatatgcagt tttccttaaa ttatctaaaa tctgctaggg
     1981 aatatcaata gatatttacc ttttatttta atgtttcctt taatttttta ctatttttac
     2041 taatctttct gcagaaacag aaaggttttc ttctttttgc ttcaaaaaca ttcttacatt
     2101 ttactttttc ctggctcatc tctttattct tttttttttt ttaaagacag agtctcgctc
     2161 tgttgcccag gctggagtgc aatgacacag tcttggctca ctgcaacttc tgcctcttgg
     2221 gttcaagtga ttctcctgcc tcagcctcct gagtagctgg attacaggca tgtgccaccc
     2281 acccaactaa tttttgtgtt tttaataaag acagggtttc accatgttgg ccaggctggt
     2341 ctcaaactcc tgacctcaag taatccacct gcctcggcct cccaaagtgc tgggattaca
     2401 gggatgagcc accgcgccca gcctcatctc tttgttctaa agatggaaaa accaccccca
     2461 aattttcttt ttatactatt aatgaatcaa tcaattcata tctatttatt aaatttctac
     2521 cgcttttagg ccaaaaaaat gtaagatcgt tctctgcctc acatagctta caagccagct
     2581 ggagaaatat ggtactcatt aaaaaaaaaa aaaaaagtga tgtacaacca cttcggaaaa
     2641 caatttggca ttatctagta aagttgaatc catgtatacc cacatagcta tcaattctat
     2701 tcctacatac gtgcttacaa gaatgtccat aaaaccctgt ttataatagc caaaagaaca
     2761 gggaacaacc ataatgcaca tcaaaagaag aatggattaa aaaaattata ttcacacaca
     2821 ggagtactat atagtattga aaacaattga agtacagcta aatgtaataa cgtaacacaa
     2881 tacaactctc agaaacataa tgttaagcga acaaagcagg ttttcagaaa atatatgcag
     2941 aataattcca tttatataaa gttccagagc atgcaaaact aaatcatttt gtataaaaaa
     3001 cccaacaaat gtgatgagac aataatggga aggaagggaa tgagaaatat taaattctgg
     3061 atggtggtta tctttgaggg aggggaatga tgtgattggg gaaatggact ttcaaaggta
     3121 atggtaactt ccttaagctg gatggtaggt ccactagtgt ttgctgcata gttatacctt
     3181 ttatcttaaa tacattttgt atctattgta acaaccactt taaagacaac cgtgctgtaa
     3241 ggcagtagct aaaaacagaa aatagtccat cgggaagggt aagatggctt tctgctgagc
     3301 acagggctag aagtgacagc ccagtgggcc ttccaactat atgccagggt gttagatgag
     3361 tagagaggag accacccagg aagtctggac aaggggtctg gcatgagctc tggagaagat
     3421 atatttgagg aacatggggt atgctagttt gttgtcctga attgctgtag agaagataat
     3481 ttaaattgca tcttagaaga cgaccctgag ggtgaatttc aacttagggc aattgtttta
     3541 gtttgtttct tattggttta aatggatact tgaagctgga taatttataa ggaaaagaga
     3601 tttatatgac ttacagttct gcaggctgta caagaaacat ggcaccagca tctgcttctt
     3661 ccccggctgc ttccactcat ggtggaaggt gaaggggagc cggatgtgca gagatcatat
     3721 ggcaagagag gaagcaagag agcgagggag aaggtgccag gctcttttta aataaccggc
     3781 tcttgaggga actaatagat tgagaactcc ttgcttctcc tccccagcac accccacccc
     3841 cagggacggc attaatgtat tcatgagggg tcttccccca tgacccaaac acctcccatc
     3901 aggccccacc tccaacactg ggatcaaatt tcaacatgag attttggggg acaaacatgc
     3961 aaactatagc agcaaccagc taccattcta aaactgccat atgattttag gatttttaaa
     4021 aagggccaaa tttaggttaa gcaaaaagtg aaaatacagt aagagaaaat agttttataa
     4081 aggctttaaa aagtgttcat aaagagcagt tcatagattt ttcacgtaac gttcatcaat
     4141 agatgctaaa actattggat gaaaagctat tgtggaatag gatcttctac aaggatttaa
     4201 atataatcct acagaagagg tatcaattat acaggggaaa atgtaccttt acaatggtca
     4261 ccacaataac caagtgattc aatttagcat cacccaaggt ggaacaccct aacattatgc
     4321 ccctcctgat gtgacttaag aattttacct atttagtttt cttgcacaaa gtgttaaact
     4381 ggaatttaat catgaggaaa ttattagaca aatcctgaat gtagtcattc tataagatga
     4441 ttgacttggg cttctcaaaa agtcagtgtc atgaaaaaaa aaaaaagggg agagacttgt
     4501 aagatacaat gaccaaatgc aatgtttgaa tctttattgt attctggata tttaaaaaga
     4561 caaaagctgg acgcagtagc taatgcctgt tatcccagca tttttgggag gtcaaaaggg
     4621 gaggatggct tgagcatagg attttgagac tagcctgggc aacacagtga gttctcatct
     4681 ctacaaaaaa tcagaaaatt agctgggcat ggtagtgtgc atctgtggtc ccagctactt
     4741 gggggggtga ggtgggagga tcacttgagc ctaggaggtc aaggccgcag tgagccatga
     4801 tcatgttact gcattccagc ctgggtgaca gagtgagatc atatctaaat aataataata
     4861 ataaaagaaa gcaacaaccc agcaaacagc tataaagata tcttcgggac aattgagaac
     4921 atttgaatat agactgcata ttagataaca atgccaaata actgttttct caggtgtgat
     4981 aatagtatat gtagaaaatg tctttttgtt ttgttttatt ttgtttttgt ttgtttgttt
     5041 gttttgagac agagtctcac tgtgtcgccc aggctggagt gcagtggcac gatctcggct
     5101 cactgcaacc tctgcctccc aggttcaagt gattctcctg cctctgcttc ctgagtagct
     5161 gggattacag gtatctgcca ccactccagg ttaatttttt ctatttttag tagagacgga
     5221 atttcaccat gttgacccag ctggttttga actcctgacc tcaggtgatt cacttgcctt
     5281 ggcctcccaa agtgttgaga ttacaggcat gagtcactgc acccagccaa aaatgttttt
     5341 ttaggcaatg catgcacaaa catttagagg ccaagtgtgt catgatgtct gcaactttca
     5401 atgttcagca aaaatcaaca tggagagaga aagagggcac acatgtggca aaatattagc
     5461 cattgtacaa ttggtaaatc tagatgacag tacacaggtg tttgttgtat tattctttga
     5521 acttttctgt agatttggaa atgttctgcg tagagagaaa tcttttttta aaaaaacaat
     5581 atctggtttt gattaatgag gctatattca aaagaaacac taaatgatgt ggccagttag
     5641 tgagaatgta gccttatctt tactgacctc attttaatat tcctactctg gctgggcatg
     5701 gtggctcacg cctataatcc cagcactctg ggaggccgag acgggtggat cacctgaggt
     5761 caggggttcg agaccagcct ggccaacatg gtgaaacccc atctctacta aaaatacaaa
     5821 aattagctgg gtgtggtggt aggcgcctgt aatcccagct actcgggagt ccgtggcagg
     5881 agaatcgctt gaacccagga ggtggaggtt gcagtgagct gagatcacgc cattgcactc
     5941 cagcctgggt gacaagagca aaactcagtc tcaaaaaaaa aaaagaaaaa aaaagatata
     6001 tatattccta ctcttattaa atgaatatag catttcttag caacttcttt tgatttgtga
     6061 gtatatattt tcttggcctc aaaattaaag taaaaagtat cctcttactc agaggaggac
     6121 aggggcaaga gcctgggacc ttatttgcta attaaaatgc acacacacac acacacacac
     6181 agaaattttg agagccattt taatataatt gcctccctag aaacatacct tttagggaat
     6241 ttttatcact aaaccacatg ttatttaaat acgtacatgt ttaacataaa tacatacata
     6301 aaattcacat gcatacttaa cacttatgtt aaatatattc aatgtatata catatgtaca
     6361 caatatatgc atatatacat gtgggtatgt ggtatgtgtg catgtgtgtg tatggccagc
     6421 tacataattt gtgggactaa gggcaaaatg aaactgtacg gccctcgttc aaaaattagg
     6481 tgtggggtgc ttctaagcac agtcttgtgc aactgcacag gttgcatgtc catgaagcca
     6541 tcctgtgtgt gtgcacatat gtgtatgaat atgtatttta tataatacat atatatgcat
     6601 gtatgtatct gagaagaaat gtttaaaagg ctacatacaa gcttttccag gtctctacta
     6661 tctgttaact aactagagac ataactcaca atatgcagtc cccactgagt gttcaccata
     6721 atttgagatt cttggcatgt taacttttca ttatggaata ttgaataatt tcaatattat
     6781 tcatacattt ctttatgttc aaacatacac aaaaatagaa taatgaaact ctacccatca
     6841 cccagctgca acaaatatca atactttacc gttcttaata catctaaccc cttacttttt
     6901 gtttgtttct tttggtgaag tatttaattg taattttttt tttaagagac aggatctcac
     6961 tctgtcaccc aggccagagt acagtggtac gatcacagct ccttgtaacc tcgaactcct
     7021 aggctcaagt gatcctcctg cctcagccgc ttgaatagct gggactacat gcatacacca
     7081 acacacccaa ctaattttta aattttttgt agaaatatgg tcttgctgtg tttcccaggc
     7141 tggtctcaaa ctcctggcct tgagagattc tcctgccttg gtcttccaaa ctgctgggat
     7201 tacaatatcc ggccctactg gaatatttta aagtaaatct caggtgttac atcattgcac
     7261 ttgtaagtac tttaaaatgt atctctagca gataaatctt tttaacaaaa ccacagcatc
     7321 attgtcacac tcaaaaaatt gacaagattt ccttaattat catataatag tctgtattgt
     7381 ttctatctca aaaatacagt tttcttggtt gttgaaatct agatccaaca ttgcatttgg
     7441 ttgatgtgtc tcctttactc tgtaaaattt acccctgcgt tttagttctt ttcggctttt
     7501 atttgtcctg tggaatttcc tccactcagg atttgactga gagtatcccc agagtgtcca
     7561 gttagaccta gaagctggat ttgatcctgg ttcatttatt ttcccccaag aatactccat
     7621 aggtgatgct atacactttc tcttacatca tttcaggagg aacatgatgt ctgattgttc
     7681 cactttcagt gattttaata ttgatcaatg agttctggtg gtaccaacta ctacaaagtt
     7741 tctcatcaat ctttcacctg atggttttag cagctattga taattgttgc ctggatccat
     7801 tatttcattt caggggttgt aaaatagtga ttttctggtt ctatcaaacc tcttgcattt
     7861 atcatctatg attcttcttt aaggaacttt ctctaaatct gaatgggaaa gatgcgataa
     7921 atatttatca aattttagag tgagttagtg ccctagcaac ctccacagtt gacaaatgag
     7981 tatttcttta aagcaaggta tggcccaacc aatactttga aactagcatg tttagaatag
     8041 agcaggagga aactatattt gaaaggtcag aagtggaaag actaagaggg cctgaacaat
     8101 aagaggacag aaccaagagg agttggcaac taattggatg tggggattaa ggaaaggtaa
     8161 gcatcaaaga ttacctccaa gtttgttaga aggttagtag caggattctg atgccattca
     8221 agtaaataca agtctcagtc agatgaaccc caagagccac atgtatttga ggggtacttt
     8281 gtctcacact tttacctgtt acatggtttt cagtaattta gaatttaagc cagtagtggg
     8341 gcgactgtac atctatcgac atggtgaggt agagcatgtt tgggaggaaa gacgttgaat
     8401 cccatttggt gacagtgagc ttgaggtgct gccagaacac tgcactgaag ataggaggag
     8461 actgtaggaa atacaagata ggaaaggtct ccactgaaat gttaactctt tctctctaaa
     8521 cggccatcca ggcctcaatg tctgcagttt ctgatctgtg attatgactt atccaaatct
     8581 tacatttctt aaaaatagtc atagatgaag ggaatcacag ttgatagtta tatggtgaca
     8641 ttattggctt aaattctaaa taactagaaa ctgtataata ggcaaaactg tgaggcaaat
     8701 aaaatgcttc tcaaatctgt gtggctctta tggggttaat ttgatttgga cctgtattaa
     8761 tttcttatgg ctgctataac taacaaatta ccacaaactt ggtggtttaa aacaacacac
     8821 atttattctc tttctgttct ggaggccaga agtctaaaat gagattcact gggctgcagt
     8881 tcactgggca aggccatgct cctctggagg cttccatgat gcatcccata ttcagtgttt
     8941 cccgagtaag ccccacccat gcaggtctgc agttttacct caacaggctt ttgcactcag
     9001 tggctctctc ctgtggtttc tatctgaaat tctcttcatt ttttttttaa taactgcttt
     9061 attgagatat aattcacatg ccatacaatt cacctataca gtatacaatt cagtagtgtt
     9121 tactatattc agagttgtgc aactatcatt tttctcaccc ccaaaagaaa ccctatgccc
     9181 gttagtattc actctgtttt ctcacaactc taggtaacca ctaatctact ctccatctct
     9241 atagatttgc ccatgctaga catttcatat aaatggaatc atacatgtgg tctttttcac
     9301 tgagtatatt ttcaaggtgc atcccagctg tggcatgaat cagcatctca ttccttttta
     9361 ttgccaaata atattctatc atatggatat gtcgcatttt atgtatccat tcatcagctg
     9421 atggacattt gggttgtttg tactttttgg ctaccatgaa taatgctact atgaactttt
     9481 gtgtacaaat cttatgtgga cttgttttca tttctcttgg atgtatattc ctaggagaat
     9541 ggctggatta tacagtaact ctttcctcat aactttgcat atcaaaatta tatccatctt
     9601 tcagaaccca aattcagtgt tatttccaaa gtgttccaac atctcccact caaaatgaat
     9661 cttctcccta gtactcccat tgtttagtac ctaattgttc ttaccagttt gtcttagagc
     9721 tcagtcattc ctacacagca cttttcttca ttatactgct aatttcatta cactgtaaga
     9781 gtggggacaa gctgttcttc ttgtatacca gaaagtagtg agtgcactgc tgtgaagaaa
     9841 gcaggaactc aaaagttaag aattttgaat gagcctataa aatgtgtcta ataaataata
     9901 atgttcattt tcaaatctca acaattaaat gtttaacaaa taacacttga aataaatgtt
     9961 tattagaaaa accaa
//
