LOCUS       NM_001347721           17024 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens dual specificity tyrosine phosphorylation regulated
            kinase 1A (DYRK1A), transcript variant 6, mRNA.
ACCESSION   NM_001347721 XM_006723979
VERSION     NM_001347721.2
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 17024)
  AUTHORS   Wang,P., Sarkar,S., Zhang,M., Xiao,T., Kong,F., Zhang,Z.,
            Balasubramanian,D., Jayaram,N., Datta,S., He,R., Wu,P., Chao,P.,
            Zhang,Y., Washburn,M., Florens,L.A., Nagarkar-Jaiswal,S.,
            Jaiswal,M. and Mohan,M.
  TITLE     DYRK1A interacts with the tuberous sclerosis complex and promotes
            mTORC1 activity
  JOURNAL   Elife 12, 88318 (2024)
   PUBMED   39436397
  REMARK    GeneRIF: DYRK1A interacts with the tuberous sclerosis complex and
            promotes mTORC1 activity.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 17024)
  AUTHORS   Pastor,F., Charles,E., Di Vona,C., Chapelle,M., Rivoire,M.,
            Passot,G., Chabot,B., de la Luna,S., Lucifora,J., Durantel,D. and
            Salvetti,A.
  TITLE     The dual-specificity kinase DYRK1A interacts with the Hepatitis B
            virus genome and regulates the production of viral RNA
  JOURNAL   PLoS One 19 (10), e0311655 (2024)
   PUBMED   39405283
  REMARK    GeneRIF: The dual-specificity kinase DYRK1A interacts with the
            Hepatitis B virus genome and regulates the production of viral RNA.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 17024)
  AUTHORS   Li,J., Xiong,N., West,K.L., Leung,M., Ching,Y.P., Huang,J.,
            Yuan,J., Yu,C.H., Leung,J. and Huen,M.
  TITLE     Nuclear F-actin assembly on damaged chromatin is regulated by
            DYRK1A and Spir1 phosphorylation
  JOURNAL   Nucleic Acids Res 52 (15), 8897-8912 (2024)
   PUBMED   38966995
  REMARK    GeneRIF: Nuclear F-actin assembly on damaged chromatin is regulated
            by DYRK1A and Spir1 phosphorylation.
REFERENCE   4  (bases 1 to 17024)
  AUTHORS   Guimera,J., Casas,C., Estivill,X. and Pritchard,M.
  TITLE     Human minibrain homologue (MNBH/DYRK1): characterization,
            alternative splicing, differential tissue expression, and
            overexpression in Down syndrome
  JOURNAL   Genomics 57 (3), 407-418 (1999)
   PUBMED   10329007
REFERENCE   5  (bases 1 to 17024)
  AUTHORS   Wang,J., Kudoh,J., Shintani,A., Minoshima,S. and Shimizu,N.
  TITLE     Identification of two novel 5' noncoding exons in human MNB/DYRK
            gene and alternatively spliced transcripts
  JOURNAL   Biochem Biophys Res Commun 250 (3), 704-710 (1998)
   PUBMED   9784410
REFERENCE   6  (bases 1 to 17024)
  AUTHORS   Song,W.J., Sternberg,L.R., Kasten-Sportes,C., Keuren,M.L.,
            Chung,S.H., Slack,A.C., Miller,D.E., Glover,T.W., Chiang,P.W.,
            Lou,L. and Kurnit,D.M.
  TITLE     Isolation of human and murine homologues of the Drosophila
            minibrain gene: human homologue maps to 21q22.2 in the Down
            syndrome 'critical region'
  JOURNAL   Genomics 38 (3), 331-339 (1996)
   PUBMED   8975710
REFERENCE   7  (bases 1 to 17024)
  AUTHORS   Guimera,J., Casas,C., Pucharcos,C., Solans,A., Domenech,A.,
            Planas,A.M., Ashley,J., Lovett,M., Estivill,X. and Pritchard,M.A.
  TITLE     A human homologue of Drosophila minibrain (MNB) is expressed in the
            neuronal regions affected in Down syndrome and maps to the critical
            region
  JOURNAL   Hum Mol Genet 5 (9), 1305-1310 (1996)
   PUBMED   8872470
REFERENCE   8  (bases 1 to 17024)
  AUTHORS   Shindoh,N., Kudoh,J., Maeda,H., Yamaki,A., Minoshima,S., Shimizu,Y.
            and Shimizu,N.
  TITLE     Cloning of a human homolog of the Drosophila minibrain/rat Dyrk
            gene from 'the Down syndrome critical region' of chromosome 21
  JOURNAL   Biochem Biophys Res Commun 225 (1), 92-99 (1996)
   PUBMED   8769099
REFERENCE   9  (bases 1 to 17024)
  AUTHORS   Schultz,S.J. and Nigg,E.A.
  TITLE     Identification of 21 novel human protein kinases, including 3
            members of a family related to the cell cycle regulator nimA of
            Aspergillus nidulans
  JOURNAL   Cell Growth Differ 4 (10), 821-830 (1993)
   PUBMED   8274451
REFERENCE   10 (bases 1 to 17024)
  AUTHORS   van Bon,B.W.M., Coe,B.P., de Vries,B.B.A. and Eichler,E.E.
  TITLE     DYRK1A Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   26677511
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP001437.1, AP001428.1,
            AP001413.1, KF457264.1, AP001421.1 and KF511415.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_001347721.1.
            
            Summary: This gene encodes a member of the Dual-specificity
            tyrosine phosphorylation-regulated kinase (DYRK) family. This
            member contains a nuclear targeting signal sequence, a protein
            kinase domain, a leucine zipper motif, and a highly conservative
            13-consecutive-histidine repeat. It catalyzes its
            autophosphorylation on serine/threonine and tyrosine residues. It
            may play a significant role in a signaling pathway regulating cell
            proliferation and may be involved in brain development. This gene
            is a homolog of Drosophila mnb (minibrain) gene and rat Dyrk gene.
            It is localized in the Down syndrome critical region of chromosome
            21, and is considered to be a strong candidate gene for learning
            defects associated with Down syndrome. Alternative splicing of this
            gene generates several transcript variants differing from each
            other either in the 5' UTR or in the 3' coding region. These
            variants encode at least five different isoforms. [provided by
            RefSeq, Jul 2008].
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on 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 :: SRR1803611.221299.1,
                                           SRR1803612.87221.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000647188.2/ ENSP00000494572.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-856               AP001437.1         45742-46597
            857-942             AP001428.1         7740-7825
            943-1139            AP001413.1         43633-43829
            1140-1232           AP001413.1         49157-49249
            1233-1421           AP001413.1         51587-51775
            1422-1569           AP001413.1         57416-57563
            1570-1662           KF457264.1         299-391
            1663-1856           AP001413.1         61217-61410
            1857-2003           AP001413.1         63966-64112
            2004-2144           AP001421.1         120-260
            2145-2451           AP001421.1         9286-9592
            2452-2576           AP001421.1         10102-10226
            2577-14486          AP001421.1         15914-27823
            14487-14825         KF511415.1         1-339               c
            14826-17024         AP001421.1         28162-30360
FEATURES             Location/Qualifiers
     source          1..17024
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="21"
                     /map="21q22.13"
     gene            1..17024
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /note="dual specificity tyrosine phosphorylation regulated
                     kinase 1A"
                     /db_xref="GeneID:1859"
                     /db_xref="HGNC:HGNC:3091"
                     /db_xref="MIM:600855"
     exon            1..856
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     exon            857..942
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     CDS             933..3197
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /EC_number="2.7.11.23"
                     /EC_number="2.7.12.1"
                     /note="isoform 2 is encoded by transcript variant 6; dual
                     specificity YAK1-related kinase; serine/threonine-specific
                     protein kinase; mnb protein kinase homolog hp86;
                     serine/threonine kinase MNB; MNB/DYRK protein kinase;
                     protein kinase minibrain homolog; dual specificity
                     tyrosine-(Y)-phosphorylation regulated kinase 1A"
                     /codon_start=1
                     /product="dual specificity
                     tyrosine-phosphorylation-regulated kinase 1A isoform 2"
                     /protein_id="NP_001334650.1"
                     /db_xref="CCDS:CCDS13653.1"
                     /db_xref="GeneID:1859"
                     /db_xref="HGNC:HGNC:3091"
                     /db_xref="MIM:600855"
                     /translation="MHTGGETSACKPSSVRLAPSFSFHAAGLQMAGQMPHSHQYSDRR
                     QPNISDQQVSALSYSDQIQQPLTNQRRMPQTFRDPATAPLRKLSVDLIKTYKHINEVY
                     YAKKKRRHQQGQGDDSSHKKERKVYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGS
                     FGQVVKAYDRVEQEWVAIKIIKNKKAFLNQAQIEVRLLELMNKHDTEMKYYIVHLKRH
                     FMFRNHLCLVFEMLSYNLYDLLRNTNFRGVSLNLTRKFAQQMCTALLFLATPELSIIH
                     CDLKPENILLCNPKRSAIKIVDFGSSCQLGQRIYQYIQSRFYRSPEVLLGMPYDLAID
                     MWSLGCILVEMHTGEPLFSGANEVDQMNKIVEVLGIPPAHILDQAPKARKFFEKLPDG
                     TWNLKKTKDGKREYKPPGTRKLHNILGVETGGPGGRRAGESGHTVADYLKFKDLILRM
                     LDYDPKTRIQPYYALQHSFFKKTADEGTNTSNSVSTSPAMEQSQSSGTTSSTSSSSGG
                     SSGTSNSGRARSDPTHQHRHSGGHFTAAVQAMDCETHSPQVRQQFPAPLGWSGTEAPT
                     QVTVETHPVQETTFHVAPQQNALHHHHGNSSHHHHHHHHHHHHHGQQALGNRTRPRVY
                     NSPTNSSSTQDSMEVGHSHHSMTSLSSSTTSSSTSSSSTGNQGNQAYQNRPVAANTLD
                     FGQNGAMDVNLTVYSNPRQETGIAGHPTYQFSANTGPAHYMTEGHLTMRQGADREESP
                     MTGVCVQQSPVASS"
     exon            943..1139
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     exon            1140..1232
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     exon            1233..1421
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     exon            1422..1569
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     exon            1570..1856
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     exon            1857..2003
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     exon            2004..2144
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     exon            2145..2451
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     exon            2452..2576
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     exon            2577..17024
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5830..5835
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /note="hexamer: AATAAT"
     polyA_site      5846
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /note="major polyA site"
     regulatory      5895..5900
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /note="hexamer: AGTAAA"
     polyA_site      5915
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
     regulatory      6019..6024
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /note="hexamer: AGTAAA"
     polyA_site      6045
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
     regulatory      8096..8101
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /note="hexamer: ATTAAA"
     polyA_site      8116
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
     regulatory      9635..9640
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /note="hexamer: ATTAAA"
     polyA_site      9662
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
     regulatory      9716..9721
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /note="hexamer: TATAAA"
     polyA_site      9738
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
     regulatory      16654..16659
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /note="hexamer: GATAAA"
     polyA_site      16677
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
     regulatory      17005..17010
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
                     /note="hexamer: AATAAA"
     polyA_site      17024
                     /gene="DYRK1A"
                     /gene_synonym="DYRK; DYRK1; HP86; MNB; MNBH; MRD7"
ORIGIN      
        1 gaccgggtcg gtccgtcgcc attttgttgg ttggtttttt tttaaaccct ttcgcttccc
       61 gcccgaataa taataaaaag ccccattgga gtgaggcggg ggtggcggcg gcaaccgcgg
      121 cgggggtatc cggggagact gctgctgtcg ctgctgctga tcgcggccca ggtcggcctc
      181 agagagcgga caccccgagc ggggggtgcg ggcgccgccg ccgccgcttc tgctgctgct
      241 gttcctgctg ctgctgttgg tgccgctgcc gccgccggcg agcaggcggg accggtgtga
      301 gtgcgagtgt gtgtgcgagg gagcgtgtgc gagggcgatt gtgcgcgcga gtgtgcgggt
      361 gtgtgcgagt gtctgtctgt ctgtgcgggg actcgggggc gggcggttcg ggctctcctg
      421 gcggaggagc cgccgccgcc gcccgggccc cggcgcttct cgctgcgcag gttcggagcg
      481 cgcgccattt tgtgagattt acaaaatcct cctcgggaag aagccgccgg cagcagccgc
      541 cgctcggcgc ccggcctcgc cgacgccgcc ctctgcgccg ggccggccgt gcggccccgc
      601 cgcctggaat cggggcccgg ggactgcggt atttgccggg gagggggctg tcgcctcccc
      661 ggccccgggc gccgctggaa ccgcgagccg aggagagact gagcaggctg cggcgcggcc
      721 aggagccgga gcgccggggg cggagagagg ctgccggggc ggcgctggct gcggaggccg
      781 cggcgggagc gcggcgcggg agcccgaggc tgagactcac cggaggaagc ggcgcgagcg
      841 ccccgccatc gtcccgtgtt atagttttgc cgctggactc ttccctccct tcccccaccc
      901 catcaggatg atatgagact tgaaagaaga cgatgcatac aggaggagag acttcagcat
      961 gcaaaccttc atctgttcgg cttgcaccgt cattttcatt ccatgctgct ggccttcaga
     1021 tggctggaca gatgccccat tcacatcagt acagtgaccg tcgccagcca aacataagtg
     1081 accaacaggt ttctgcctta tcatattctg accagattca gcaacctcta actaaccaga
     1141 ggcggatgcc ccaaaccttc cgtgacccag caactgctcc cctgagaaaa ctttctgttg
     1201 acttgatcaa aacatacaag catattaatg aggtttacta tgcaaaaaag aagcgaagac
     1261 accaacaggg ccagggagac gattctagtc ataagaagga acggaaggtt tacaatgatg
     1321 gttatgatga tgataactat gattatattg taaaaaacgg agaaaagtgg atggatcgtt
     1381 acgaaattga ctccttgata ggcaaaggtt cctttggaca ggttgtaaag gcatatgatc
     1441 gtgtggagca agaatgggtt gccattaaaa taataaagaa caagaaggct tttctgaatc
     1501 aagcacagat agaagtgcga cttcttgagc tcatgaacaa acatgacact gaaatgaaat
     1561 actacatagt gcatttgaaa cgccacttta tgtttcgaaa ccatctctgt ttagtttttg
     1621 aaatgctgtc ctacaacctc tatgacttgc tgagaaacac caatttccga ggggtctctt
     1681 tgaacctaac acgaaagttt gcgcaacaga tgtgcactgc actgcttttc cttgcgactc
     1741 cagaacttag tatcattcac tgtgatctaa aacctgaaaa tatccttctt tgtaacccca
     1801 aacgcagtgc aatcaagata gttgactttg gcagttcttg tcagttgggg cagaggatat
     1861 accagtatat tcagagtcgc ttttatcggt ctccagaggt gctactggga atgccttatg
     1921 accttgccat tgatatgtgg tccctcgggt gtattttggt tgaaatgcac actggagaac
     1981 ctctgttcag tggtgccaat gaggtagatc agatgaataa aatagtggaa gttctgggta
     2041 ttccacctgc tcatattctt gaccaagcac caaaagcaag aaagttcttt gagaagttgc
     2101 cagatggcac ttggaactta aagaagacca aagatggaaa acgggagtac aaaccaccag
     2161 gaacccgtaa acttcataac attcttggag tggaaacagg aggacctggt gggcgacgtg
     2221 ctggggagtc aggtcatacg gtcgctgact acttgaagtt caaagacctc attttaagga
     2281 tgcttgatta tgaccccaaa actcgaattc aaccttatta tgctctgcag cacagtttct
     2341 tcaagaaaac agctgatgaa ggtacaaata caagtaatag tgtatctaca agccccgcca
     2401 tggagcagtc tcagtcttcg ggcaccacct ccagtacatc gtcaagctca ggtggctcat
     2461 cggggacaag caacagtggg agagcccggt cggatccgac gcaccagcat cggcacagtg
     2521 gtgggcactt cacagctgcc gtgcaggcca tggactgcga gacacacagt ccccaggtgc
     2581 gtcagcaatt tcctgctcct cttggttggt caggcactga agctcctaca caggtcactg
     2641 ttgaaactca tcctgttcaa gaaacaacct ttcatgtagc ccctcaacag aatgcattgc
     2701 atcatcacca tggtaacagt tcccatcacc atcaccacca ccaccaccat caccaccacc
     2761 atggacaaca agccttgggt aaccggacca ggccaagggt ctacaattct ccaacgaata
     2821 gctcctctac ccaagattct atggaggttg gccacagtca ccactccatg acatccctgt
     2881 cttcctcaac gacttcttcc tcgacatctt cctcctctac tggtaaccaa ggcaatcagg
     2941 cctaccagaa tcgcccagtg gctgctaata ccttggactt tggacagaat ggagctatgg
     3001 acgttaattt gaccgtctac tccaatcccc gccaagagac tggcatagct ggacatccaa
     3061 cataccaatt ttctgctaat acaggtcctg cacattacat gactgaagga catctgacaa
     3121 tgaggcaagg ggctgataga gaagagtccc ccatgacagg agtttgtgtg caacagagtc
     3181 ctgtagctag ctcgtgacta cattgaaact tgagtttgtt tcttgtgtgt ttttatagaa
     3241 gtggtgtttt ttttccaaaa acaaagtgca aagctgcttg aatcaggagg agattaacac
     3301 actgaaccgc tacaagaggg caaagctgat ttttttttta acttgaaaag attgcaaagg
     3361 gacattgaag tgtttaaaag agccatgtcc aaacccatct tcatggatag ctcagaggta
     3421 tcctcttttt gctcccccat tttaacttgc cacatcccag tcacagtggg gtttttttgt
     3481 ctttctattc agcaaaagtt aatattcaga tgttggtctt ggtcatttgc caactaattt
     3541 taaagtaaaa ggcactgcac ataatttgca taaagggccc catgagggtg tttttttttt
     3601 ttctttttgt cccccccatc cccctttttt tttgttttgt tctgttttgt tttgggtggg
     3661 agggtgggaa atttgggttt ttaagtcctc taaacacact tgggcacgga aatgcagtac
     3721 tgtaaggaag agggacctcc agcttccaca aacaccatct tcagctgtat gaaagggacg
     3781 gttgtggtga agtttgtcag gcacagtaag catgctgagt ggcggggatc agaactctcc
     3841 tatctgaacc tactgaggag caaagcagca attacatggg atcctgtggc tctcccgttg
     3901 cagaggccac aggaagatag gatggaacgt gactggtctc ctaaccaagg tgcactgaga
     3961 agcaatcaac gggtcggtcg tggccagtcc tggggaggtc tgagtggtgg tctttgggat
     4021 aacctttggc cttatggatt tggactcgaa attagaagag cctaccattt cagatgcaat
     4081 cacttttgga catgcttttg cagacagtcc ttaatgctga aaacacagag aatgggtaat
     4141 tcaagaggcc tttcttttaa aatagacttt tgtgacccac taattgtaag gtattgcaag
     4201 gtcactttgc gtgtgtcata aagttgactt ccttattggt tgaaggtcac agaagtagtg
     4261 gtttgctttg atggaaatag ctacagctgt gtcccttcct gctttttact ttttcttttg
     4321 ctttttctcg gcacgtggta tctccaccat ttcttctgca caaagatgtc ttctgttcat
     4381 cctgaacatt tttaaaaaat gcagaatttt atgtgactgc ttttttgcct cacaattatg
     4441 ctgtgaattt tacaaaaatt tattttcttt tttgataatt tattgtacca aagctgtttt
     4501 tatagcacat agatgtctgt aaccaataat gtagcagttc tgcactttga cacaaggtgt
     4561 aactagacca tttttaaatg tcagttgaaa attatggctg tactattgct taaacaaaac
     4621 tggaactgtt gttgaatcca tagccaatac atttacagca atctgtgtac tgaacatagt
     4681 agattgacat ctaattcaag attacaacat ctgttacatt ctaagtgtgt tcaggcttct
     4741 gaaggtaaag ggacactgga tccagaagct atggaaccag cagttgattc ttgtattcct
     4801 gattaaccta cttgtaaact tgaaagcaag accttgattg caccaacagg tccagagtat
     4861 gagtgcaagc aaagcagaac tctcatgcgt gacctgagca gacaggctgg tatttaacag
     4921 gtgcctcgtg ttgagattac gctgccttaa tgtaacacag tctggcagtt gctaaatttg
     4981 tgttcccatt ttaaattgac caattttggg gtgtgacact tttgagcggt tgaattggga
     5041 gaatgaagat aagtaattta cctgtccagg atcaaaagaa gcctagaaaa gaagcagtaa
     5101 tctacctctg ccgataacct gtttaagatg actcagcaga acaccgcgtt tcattctatt
     5161 ggtcaattcc atgtggctga ctaggtcaat tttttttctg aacaaaagca ggtttttata
     5221 tgtaaacagt gagaaaagaa aggctaaaca ctatgtaaat gtgaatggaa acttggaaat
     5281 actcgttttt ataaactaca aaaacttttt gttgtttatc aggaaatcca tatttatttt
     5341 gtaattaact gtcaagcctg tggatgattt ttttgaactt ggtagttcat aaaggtttac
     5401 agtgaataaa aggatatcat cttgagtata gcaatatcaa aaggaattca gtagttactg
     5461 ctgtttagga atataaggtt aagatatcat atgggtcagg tcattttttt tttctgtgct
     5521 ggttgccaca tcttagcaag caccaaaaaa ctaaagcagt ttttaaaccg atatttacgt
     5581 aaagaaaatc ataaaatcca atgcttctgc atactgtgtt atgttacagt ccagttttgt
     5641 gtgctttact acacagtttg gttacaggac ttctgtgcat tgtaaacata aacagcatgg
     5701 aaaaggttaa atacctgtgt tcagattgta agatctagtc cggacttgct gtgtatattg
     5761 taacgttaaa tgaaaaaaga accccccttt gtattatagt catgcggtct tatgtatgat
     5821 aaacagttga ataatttgtc ctcagactct ttactatgct tttttaaaaa ttaatttaag
     5881 aaaaatgtaa acatagtaaa aatcttccta tgcaattaaa ctggtccagg tctggtaggt
     5941 atagtatcaa agttgagtta aatgtgtaaa aaggaaacta tttgagatac attgacatag
     6001 gcatcagcaa tctctgaaag taaaaattgg aggtttaaca gatcattttg atttttcaca
     6061 ttgatttttt tatttgaatg tttacataat tttgtgattc aaaatgctca tattttagtt
     6121 ggtagcattt cgactggatg tgagggtctg atggttttct ctgatatgct ttgacgtgct
     6181 tggatgaagg aaggaatacg aatactcatt cttccttccc taactcctcg tacggggcca
     6241 tatcagaatt ctagaattct tgccactgtg attcaattgc taacctaaag tcttctcttt
     6301 ttacaaattc acctgcttca gtatatatta aggtggcttt cgagaggcaa gatgcttatt
     6361 taaaagttaa gcgtgaatct gtaaaattaa ggttggttgc gtaaagttga agttaaccac
     6421 atgtaagaaa ggaaaacttc cattagtttt cttcttaggg tgtgagaatt ttacctaggc
     6481 acatggatat tgggctgaaa aaaaaaaacc gacattttta tttaaaacta catgtaaaaa
     6541 atcatgaaag attcagtaat tatgttaggc tcacaagtga ccattgagtt tgcccctgta
     6601 ctgcttccca gcttttgtgg tgttgaactt ttctgttctt ccaataggga gatacataat
     6661 caaaatacac acgaagacga gatagcaggc actcagttct aggccagttt ctcagtttcc
     6721 tttgggcctg cctttatttt gatagtcgca gaatgcaggt tcagatgcga tccggtgcat
     6781 tctgggtggt atccccatag acagaataca agttcaagac tcatttttat gtccattttt
     6841 atagtggtag actgtatgta atagaccaga tggttcattc caaatacatg acttggtctt
     6901 actgctatat atgaaggaag tttgaaaatg taatggggac aaaagccgtg cgtgacttcg
     6961 gtatacccag acttcattca gatttcttaa aaatctgcta gggatgtctg ttgaccagac
     7021 gttggaaaac ctttggtgtc agggagagta gaggagaagt tctgattttc ataaccctgg
     7081 tttcttatct aggcctgttt ccttgcgtga aaacatacat caccaagtaa tttgtagtac
     7141 aaagaacaag agaagaaacc ctaagaagat agcttatttg ttatcctccc ttttaatgac
     7201 taaccttaat ccaaatgaat ccactgagaa ccagcctgtg gatgcctact gggctttcac
     7261 cctggaccag gaatttttga cgtatgcctg tgttgaaggc actggatgct tgttttgtgg
     7321 aagacatgtt cattgaggta agtggctcat cgcttggtgt gtttggctct ctttggcatt
     7381 atgcatagcc aaggtcccag attttggctg ctctcagtgg gtgttcttgc atcagaactt
     7441 taaaaaaaat aacactacct taacactgag actgtcaggt atttgtcagt atttatttct
     7501 aatttcctac tttaaatctt aggagacaaa gtgtttctcc aactggacgc tgatttgaaa
     7561 cacaactaga atgctacagg tctctcttcc agtatgcagc tgctgtacct gaaaattttt
     7621 ccccataatt tcccatcttt agggtatgtc cctgttatca ggtgtggaat taatgtgggt
     7681 aaatttccat ttcagttgaa tttcctgtca tccccagcaa aacctgtgaa tccttcttca
     7741 aagcatagag gaggcagaga caagtcttaa accggcttcc cttcgctttt accaggtagc
     7801 ctggttcagt cccagctggg tcctgaagga gcacagtact agagcctgag tcatgttgac
     7861 tattaataaa gtgcattaag tttgggtcag gcaaagtggt ggcaaaagtt catgatgcag
     7921 gacagaggaa acaagtggac aagacaagtg gagcccagct ctgttcgcat gggaggccgg
     7981 gcgatgctgg catgggtgtg gttggccgag ttctcatagc tagagaaagg ccgtgtaggt
     8041 ataagtgctt aatgtttcat ctgtctgaaa gaccagctat ttgataatct tcccgattaa
     8101 atttctaaaa ttgctacttt gggaattttt ttctttattc ttgtaaagtt ttgcttccat
     8161 tatatactca ttcattagtc agtgtacttg cccctgaatt ccatatctga aactgcagtc
     8221 acgggagatt cagagccaag ggcaaaataa agtggcaggc actgggtgtg tgtggtagtt
     8281 ctgcactagg gtggccagga agcagccaag caggtgtgcc gggcagggag ttgttaatga
     8341 acacccaggc aagaggacgg gcctgagcct gagtgtggcc agcagaaagt gttgagttgc
     8401 ttaaaagaga ccctgggagg atgaatttgg aatcatcatc cactcactgt tggacagaaa
     8461 gactgcagag aagggcactg ctggggtggg gtttgttaac tccctctgaa atgaaagaaa
     8521 atacctctag tggcatgaaa cggctaagtt ttttttaatg ttacttcttt aattttagag
     8581 acggtgtctg gctttgtcac gcaagctgga gtttggtggt gtgattgcag ctcactgcag
     8641 ccttaaacaa ctgggctagg tgatcctccc atctcagcct cccaagtagc tgggactacc
     8701 tgtgcacacc accatgcctg gctgttttta atacggggtt ttgctgagtt gctcaggcgc
     8761 tcctcaaact gctggcctca agtgatcctc cagcctgggc ctctcaaaca taaataggct
     8821 gggcgtggtg gctcacgtct gtaaagattt aaagcggaaa agcggaatgc agtgaaatag
     8881 catgagaaag agcgttttta tgtacatcac agacaagcct tgttctgctg aagaggtgat
     8941 gccacgaggt ggggaggagc tcacttcagg caccactccc acttccattg cccgcaaatc
     9001 caggaaagaa atgactaatg aactctagtg atcgcaaact gctcaatcgg tactcatcaa
     9061 tttaaaatga ctgtccagcc ttgctgcaca ctaaactcat ctgtagaact ttataaaacc
     9121 acggatgacc atcacactag caggatttta gattcagagt tggggtgggg cctggagctc
     9181 tgttttctga aactttgcgg gccattctga acctgcagcc aggcaggact ctggcaagaa
     9241 gaggcgtgtg gctaatatga cggaagtctg aatccaagga cttttttttt tttttttttt
     9301 ggagacagtc ttgctttgtc tcccaggttg gtgtgcaggg gtgtgatctc ggctcactgc
     9361 aacctccatt tcccagattc aagcgattct cgtgcctcag cctttcaagt agctgggatt
     9421 acaggtgcac accaccacac ccagctaata gtatttttga tagagagggg gtttcgcaat
     9481 gttggccagg ctggtcttga actcccgact tcaagctatc cacctgcctc ggcctcccaa
     9541 agtgctggga ttacaggcgt gagctacttc acccagcccc aagaacatct tgaaatggag
     9601 tttgattacc aaagtttaca tagagtaatg gataattaaa attttcaatt tatggtgcat
     9661 tacaaaatgt tataaacaag cctccgggaa aggcagaaat tgccagatgt aagtatataa
     9721 aacttacaca gtttgttcct ttttgttgtc ttcccttgtg gagatgggtc agtgtaacat
     9781 cctattcatt aatagctctc agatgtccca tgagaatggc acatgttatt tcccaacagt
     9841 gggaatggaa ttagttcctt tatatctcag tctcatctgg tcttgtaagc cggtgaaggg
     9901 tttcccaggg caccagccac cagctctgta tagtagttac agtttccctc tctagaatcc
     9961 caaagaggtt cagatcccac tgctcctctc attggcttcg tgaccctggg tacgctgctc
    10021 aacttgcgca aggattactg tccgctttgt acaatggaga tacctatagt gtccacttag
    10081 gagatgctgt gcatgcctca gtgaggtaat gtccgcagaa agcacaatgc ctagtatgta
    10141 gaaagtgtcc gataaatata atatgcggct aaacagcgga gtccacagcc tgaatggaac
    10201 ttctttttct acgtaaatac agcaaacaat gcagggaaat gaggtggaca gtgttctccg
    10261 tggagggcta aacagcattg ctttccagct gacttttatt tttggagtct gggactaggt
    10321 gttaacattc ctttactagt tggttttgca taccgcacag tccctgcatc tatttaagag
    10381 ttttgaggtt tgttgtggga agtttttttt tttttttttt tttttgaggc ggagtctcgc
    10441 tctgtcgccc aggctggagt gcagtggcgc gatctcggct cactgcaagc tccgcctcct
    10501 gggttcacgc cattcgcctg cctcagcctc cagagtagct gggactactg gcgcccgcca
    10561 ccacgcccgg ctaatttttt ttgtgtattt ttagtagaga tggggtttca ccatgttagg
    10621 caggatggtc tcagtctcct gaccttgtga tccatctgcc ttggcctccc aaagtgctgg
    10681 gattacaggt gtgagggagt ttttcggtag tttgctttgc cttgataaac tatatgatat
    10741 ttaaatgttt tataaggatg ggttttcagt agaatttctc tgtacaacct cagggagact
    10801 gcctggagga ataactgtgg taagggtctg tttttgaaca ggcatggtca ttagaccctt
    10861 gtgatcacgc atccaggggc cagtccccac cctttgctcc cactccaagg aaagtctgtt
    10921 acatttttag ccttcagagg tttgatgtag ataggaagag atgagggtga cagaaatcag
    10981 ctcttaagtt tataaataaa acagggatat tatcggggaa gcttttgaaa tgtaataggt
    11041 tgtaacccac attttgaaag cagtaaggaa ataattgctg cttttttctt cttctttatt
    11101 ctgttgactt tgttgataat attaggtgac tacatcgagc ctgggttctc tcagtattag
    11161 cctgttattc ctaaagtatc atcctctcct tgtatcaaat ataaggacaa aaatgtctta
    11221 ggataaaagt ctgtttgttt gcattagact atacatgatt tgcattacaa tgggccgtgg
    11281 atttggatgg atgatgaagc tgaaacaagg gacctaatca tgggatttaa ctgttcactt
    11341 caggtagata agatatttct gggagaagta aattggatga gcttttgtgc ttcccagcag
    11401 ctccaggtct tgtccctggc cagtctgggc agctctgcgc tcagaggcct ttggcacgat
    11461 gggtcctccc agcaggggct ccagcgctca ccgctgggtg agatctacag ggctcagtgc
    11521 gcttggagtc ctggattcct ccaggactgc tactgtattc caattgagtg gtggtttgct
    11581 cttcacagag cgcttacatg ggattcttac cttctgactg gagtgtcacc ctcgcccagg
    11641 aatgtgggtg ctggagagac gggctacctc tttctgtagg cggatgtttc tgaaggcatc
    11701 tcccactgat tatgtaatga cagctactta acatcttctg tagtcttgaa gaattcagat
    11761 gaggagcttg tccagggagg gctcccacgt gcgtattcac taattgtggt ctttctcccc
    11821 agctcggttt tgtttgcgta ttagagttct gaccatcttc actagaagtg ggggcggcta
    11881 gcagtgacta gatgcaagaa gcaaaacggt aaatttcctt ttactggcaa aattaaaaca
    11941 gtgaacttga aatatctccc ctactccctg cagagacact ctgaatcaaa gaaaacaatc
    12001 agtactaacc ctggaaacaa tttaaaaatg aacaaaaagt cctaccctga agaagaagaa
    12061 tgtcttacca gcaaacggtc ttgggacagc tggtgtgaga actatataag agaaatcaac
    12121 aaatattaat tgaacaccag tcatgtgcaa agcacttagc taggtcttag ggatgaggac
    12181 aaaaagcatg tcacattttg ttgttataag tgggaaagat aagtaattac aagtaagccc
    12241 agtgttttta aaagagtgtg aacagagacc ttattctaat ccagagaggc tgtgaagtgc
    12301 tgtattccca aggaactgaa gttctagctg atacctaatg gaggaatggg tgttatcctg
    12361 gtgggaatgc cctagaatct aggagaagac aacaggccat tcgaaggtga ggaggcttgc
    12421 cagcatcagt ttataagtgg acagagtcga gagctattta ggaaggagag ctgacagacc
    12481 tcggggactg aatggatgct gggagtaggg gtgaaaagag aggagtcagg cttcctccca
    12541 gagtttgagg actttgagtg ctaagggctt gtaggagaac gttgtggaga tgtccggtag
    12601 gcatctgaaa gaatggatgg aggaggggaa agtcgggcct gggaatggcc aatttctggt
    12661 cattctcata taggcaactg atggcgaagg ggatgaccta gagggagttg ggaggacagc
    12721 ctaggatacg taaataagag aatcttgtat gttctaaaaa ttaacatcat tgcagcttcc
    12781 tcagccctag gatggttttt agatctatca agggatagaa gattgtccag ccccttgctg
    12841 cccagtgtag tcagtgggct gacgacatta gcatcacctg ggtgcttgct agcaatgcaa
    12901 aatctcaggc cccagcccag accactggat gagaatctgc atttgaacaa ggtccccagg
    12961 tcattcatgc acattcaaag tcagagacac tgccccaaca cctcacttta gagtgagaaa
    13021 acttaacagg tttaagcaac ttgcagaaga tgacacaact gaccagcgac agtctgtctt
    13081 ctagtcaggc ctctttccag ttctccacgc tgaccttgac tttcgagatc acataccaag
    13141 accttcagct ggatggtccc tgtagctgct gtgaccacta gaagcagggt taggggcgag
    13201 actaatttaa tatcaattaa tgtagacact aggcttaggg ctagggaaaa tgtagtgaag
    13261 gatgcctgta ttgtcctaat gaaccacact ggtgcctaca aaatttttat tttggcaaaa
    13321 ccgtccatga atttggagat gttgaacagg tttctctccg acaatcgtct cgtttaattg
    13381 tgaaactaga atcacttcca ggaagctctg aagaatcaag tctgagtgat gcaatgctgc
    13441 ttcctccttc cttctcaaaa gcctgctctt tgcccatttc tctgttccca aggtcatttt
    13501 ctccccttct tgtttccagg atccacagtt cctgctctgc ttccgctttc cccactgctg
    13561 gttcaggctg tctgcagcag cagcagctcc agggtgctgg gacactgctg ggtgacgctc
    13621 cacagtgtgt gcttccccat gtggcttcca cagtcccctc ttgcttctcc cacatgttag
    13681 tcttcataga ttagtcttca tcaattctta gtattatttt ttagggatag ggtcttgctg
    13741 tgttgcccag gctgcagtgc agtggtatga tctctgctta ctgcagcctc cacctctggg
    13801 actcaggcga tcctcctgcc tcagcctccc aagtagctgg gaccacaggc gcatgccact
    13861 gtgcctggct aaattatttt atattttgta gagttgaggt cgcacttttt tgcccatgct
    13921 ggtcttgaac ccctgggctc aagcgatcct tctgcctcag cctcccatta cgggcaggag
    13981 ccactgcaca cagctgatga attttcgttt aggccccttt ctttgtgaga gggggcccca
    14041 ggattatgcc ccgggattaa aagaagctgg gaggctctcc aggaccctga acaaaggtgg
    14101 aagtagggtt gtaaatggaa gaaaaaataa gagagattca ttatgttcta atgactatga
    14161 gggaagcttt agtttttgtc tccctgaagc atcaacctgc tttcctgctg ctgttatcac
    14221 atccttccag ggctatcggc tgttcaggaa caggagagct ctggaagagc agggacgact
    14281 ttggcttctg tttcctgccc attgcagatt aggcatcagc aaggtaccct cctgtttttg
    14341 tatggctcac caaactaagg gtgattttca cattttacat ggctgaaaaa catcaaatga
    14401 tatttcagga catagggaaa ttatatgaca tttgaatttc agtgtccata aatgaagttt
    14461 tattggaaca taaccacatt catttgcaag ttgtccacgg ccactttggt gctactgtgg
    14521 cagaattgag tagttgctgc agagaccgta tgatgagaat atgtggcatt ctcatcattt
    14581 tgccctgccg ctctgtgcaa tgtaaattgc agtgacacag ttataactca gcagcatttt
    14641 gaatgccact tgtattccca tgctacaaca ttttattttt tattaccaat atatacaaga
    14701 aaagtggatt tcaaatatca ttgtgctttt aaggtacaat ggagtatgaa ttgttactga
    14761 attaggcagc aaagtgcaat gacatggtag ctgtcctaag gaacacaata caaccaggtg
    14821 cagtggctca tgcctgtaat cccaacgatt tgggtggctg aggtgggaga atcacttgaa
    14881 cccaggattt ggagaccagc ttgggtggta tagtgagacc ccccatctcc acaaaaagta
    14941 aaaaaaaacc aaaatacatg ttgttacttc ccatcttagc actcatcaag atatttctaa
    15001 ttcacaagaa agcaatggtc agaaaaatta gaaaatttaa aattgaatat ctcatcacag
    15061 aatttattca caaaaataaa aaatgaaaat gaagctacaa ccaaagtaag tttcagatgg
    15121 ctcatttgtt agccaagcaa ggaaagtcac ttatggtgaa ttaattaaat catgcttgat
    15181 tactgcagct gaagaaacat gctcagagaa agtaaacttg tttattggcc tttccacgac
    15241 aacagttgct caaagagttg acattaggaa tgacatcagt agtcgactaa aaaggcaaat
    15301 ggttttgagt ggtttcccct gactctcatg acaggggtca ccatatgtta tgcacactgc
    15361 tccgctattg ctctttattt gaggagccag taccaagttg gaagtaactg aagaattggc
    15421 ctctatcaat agtcttatgt ggaacaacta ctggcaaaag tattttcaaa gctgagaaaa
    15481 ctggtcaggt gtggcggctc atgcctatag tcccaacact ttgggaggcc aaggtgggca
    15541 gatcacctga ggtcaggagt ttgagacctg cctggccaac atggtgaaac tacatctcta
    15601 ctaaaagtac aaaaattagc cgggcatgat ggcatgcact ggtaattcca gctactcagg
    15661 aggctgaggc aggagaatcg cttgaaccca ggaggtggag gttgcagtga gctgagattg
    15721 caccactgta ctccagcctg gatgacagag tgagaacatt gtctcaaaac aaaaagttga
    15781 gaaaacgaat tcagtacacc ctgaagtgga atctgctaag atgtgttatg actgttggta
    15841 gtggaaatat atgtgtgtat tagtccattt tcatactgct ataaagaaaa gcctgagact
    15901 gggtaattta taaagaaaaa gaggtttaat ggactcacag tcccgcatgg ttggggaggc
    15961 ctcacaatcg ttgtggaagg taaaggagaa gccaaggcaa gtcttaggtg gcggcaagca
    16021 agagagtgtg tgcaggggaa ctgcccttta taaaaccatc agatctcatg agacttactc
    16081 actattatga gaacagcatg gtaaaatcct gcctccatga ttcagttacc tcccactggg
    16141 tcctacccat gacacgtggg gattatgggg gctacaattc aatgagattt gggtggggac
    16201 acagctaact catatcagtg tggaatagaa aatggctcag ttggacaact tacaaagctt
    16261 gtaataatat aaggtgttaa agcctataga ttattcattg tattatttaa gtcaacagat
    16321 actttgtgag aaatatttga atctatcatg cattattgaa ccagtattgt caatagtgaa
    16381 cttcctttag ctcttgtgga cttcactatc aacagctctc atgaattttt gtcagaaata
    16441 ttagctgaat atcccgacat ggcctgtaat acagcagttc aatggtttag tagtggtaaa
    16501 gtttcattta agttttgagc tcaggacaaa gattgaaatt tttctgaatg agaactgccc
    16561 cgaaccaccg ttactaaaca ctgaatagtt ttggaaattc acttttgctg cagacttgat
    16621 agtgtttctt aaggaattca gcctaaacca caagataaaa acagtgttta tgtgaaactc
    16681 ctactgtgtt aagtgatttc aagaagaact attgtttgaa tcacaactaa tgttactgct
    16741 ttaagctctt cccatgttgt taaaagttaa aaaaagaaga gctccattcc cacacacatt
    16801 tgccacagat acattatctg agcccaaact acagtttgag cagtgtgtta gggacctcaa
    16861 tgcaaaccca aaagaaattt ttatatttca gaatccattg atctgcattt gagaagtgat
    16921 taatgtgttg aaaggcaact atctaaagaa aaatttaata gagtctaata gaatcttata
    16981 aaaatgtata aatgtgtttt atgtaataaa tatgctaagc taaa
//
