LOCUS       NM_001374520           11082 bp    mRNA    linear   PRI 07-APR-2024
DEFINITION  Homo sapiens dermatan sulfate epimerase (DSE), transcript variant
            15, mRNA.
ACCESSION   NM_001374520
VERSION     NM_001374520.1
KEYWORDS    RefSeq.
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 11082)
  AUTHORS   Listik,E., Xavier,E.G., Silva Pinhal,M.A.D. and Toma,L.
  TITLE     Dermatan sulfate epimerase 1 expression and mislocalization may
            interfere with dermatan sulfate synthesis and breast cancer cell
            growth
  JOURNAL   Carbohydr Res 488, 107906 (2020)
   PUBMED   31972438
  REMARK    GeneRIF: Dermatan sulfate epimerase 1 expression and
            mislocalization may interfere with dermatan sulfate synthesis and
            breast cancer cell growth.
REFERENCE   2  (bases 1 to 11082)
  AUTHORS   Tykesson,E., Hassinen,A., Zielinska,K., Thelin,M.A., Frati,G.,
            Ellervik,U., Westergren-Thorsson,G., Malmstrom,A., Kellokumpu,S.
            and Maccarana,M.
  TITLE     Dermatan sulfate epimerase 1 and dermatan 4-O-sulfotransferase 1
            form complexes that generate long epimerized 4-O-sulfated blocks
  JOURNAL   J Biol Chem 293 (35), 13725-13735 (2018)
   PUBMED   29976758
  REMARK    GeneRIF: DS-epi1, DS-epi2, and D4ST1 form homomers and are all part
            of a hetero-oligomeric complex where D4ST1 directly interacts with
            DS-epi1, but not with DS-epi2. The cooperation of DS-epi1 with
            D4ST1 may therefore explain the processive mode of the formation of
            iduronic acid blocks.
REFERENCE   3  (bases 1 to 11082)
  AUTHORS   Liao,W.C., Liao,C.K., Tsai,Y.H., Tseng,T.J., Chuang,L.C., Lan,C.T.,
            Chang,H.M. and Liu,C.H.
  TITLE     DSE promotes aggressive glioma cell phenotypes by enhancing
            HB-EGF/ErbB signaling
  JOURNAL   PLoS One 13 (6), e0198364 (2018)
   PUBMED   29864158
  REMARK    GeneRIF: Study showed that DSE is frequently upregulated in human
            glioma tissue and cell lines and associated with a worse tumor
            grade and poor overall survival. Its knockdown suppresses malignant
            phenotypes, whereas DSE overexpression enhances glioma cell
            malignancy, both in vitro and in vivo. Mechanically, DSE modulates
            HB-EGF-induced EGFR/ErbB2 activity and downstream signaling.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 11082)
  AUTHORS   Tykesson,E., Mao,Y., Maccarana,M., Pu,Y., Gao,J., Lin,C., Zaia,J.,
            Westergren-Thorsson,G., Ellervik,U., Malmstrom,L. and Malmstrom,A.
  TITLE     Deciphering the Mode of Action of the Processive Polysaccharide
            Modifying Enzyme Dermatan Sulfate Epimerase 1 by Hydrogen-Deuterium
            Exchange Mass Spectrometry
  JOURNAL   Chem Sci 7 (2), 1447-1456 (2016)
   PUBMED   26900446
REFERENCE   5  (bases 1 to 11082)
  AUTHORS   Muller,T., Mizumoto,S., Suresh,I., Komatsu,Y., Vodopiutz,J.,
            Dundar,M., Straub,V., Lingenhel,A., Melmer,A., Lechner,S.,
            Zschocke,J., Sugahara,K. and Janecke,A.R.
  TITLE     Loss of dermatan sulfate epimerase (DSE) function results in
            musculocontractural Ehlers-Danlos syndrome
  JOURNAL   Hum Mol Genet 22 (18), 3761-3772 (2013)
   PUBMED   23704329
  REMARK    GeneRIF: study identified a homozygous DSE missense mutation
            (c.803C>T, p.S268L) in a male child with musculocontractural type
            of Ehlers-Danlos syndrome; data indicate mutation affects the
            epimerase activity, resulting in reduced dermatan sulfate (DS)
            biosynthesis and an increased synthesis or an accumulation or
            reduced conversion of chondroitin sulfate
REFERENCE   6  (bases 1 to 11082)
  AUTHORS   Pacheco,B., Maccarana,M., Goodlett,D.R., Malmstrom,A. and
            Malmstrom,L.
  TITLE     Identification of the active site of DS-epimerase 1 and requirement
            of N-glycosylation for enzyme function
  JOURNAL   J Biol Chem 284 (3), 1741-1747 (2009)
   PUBMED   19004833
  REMARK    GeneRIF: Identification of the active site of DS-epimerase 1 and
            requirement of N-glycosylation for enzyme function.
REFERENCE   7  (bases 1 to 11082)
  AUTHORS   Maccarana,M., Olander,B., Malmstrom,J., Tiedemann,K., Aebersold,R.,
            Lindahl,U., Li,J.P. and Malmstrom,A.
  TITLE     Biosynthesis of dermatan sulfate: chondroitin-glucuronate
            C5-epimerase is identical to SART2
  JOURNAL   J Biol Chem 281 (17), 11560-11568 (2006)
   PUBMED   16505484
REFERENCE   8  (bases 1 to 11082)
  AUTHORS   Sasatomi,T., Suefuji,Y., Matsunaga,K., Yamana,H., Miyagi,Y.,
            Araki,Y., Ogata,Y., Itoh,K. and Shirouzu,K.
  TITLE     Expression of tumor rejection antigens in colorectal carcinomas
  JOURNAL   Cancer 94 (6), 1636-1641 (2002)
   PUBMED   11920522
REFERENCE   9  (bases 1 to 11082)
  AUTHORS   Tanaka,S., Tsuda,N., Kawano,K., Sakamoto,M., Nishida,T.,
            Hashimoto,T., Shichijo,S., Kamura,T. and Itoh,K.
  TITLE     Expression of tumor-rejection antigens in gynecologic cancers
  JOURNAL   Jpn J Cancer Res 91 (11), 1177-1184 (2000)
   PUBMED   11092984
REFERENCE   10 (bases 1 to 11082)
  AUTHORS   Nakao,M., Shichijo,S., Imaizumi,T., Inoue,Y., Matsunaga,K.,
            Yamada,A., Kikuchi,M., Tsuda,N., Ohta,K., Takamori,S., Yamana,H.,
            Fujita,H. and Itoh,K.
  TITLE     Identification of a gene coding for a new squamous cell carcinoma
            antigen recognized by the CTL
  JOURNAL   J Immunol 164 (5), 2565-2574 (2000)
   PUBMED   10679095
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL050331.11 and Z84488.1.
            
            Summary: The protein encoded by this gene is a tumor-rejection
            antigen. It is localized to the endoplasmic reticulum and functions
            to convert D-glucuronic acid to L-iduronic acid during the
            biosynthesis of dermatan sulfate. This antigen possesses tumor
            epitopes capable of inducing HLA-A24-restricted and tumor-specific
            cytotoxic T lymphocytes in cancer patients and may be useful for
            specific immunotherapy. Mutations in this gene cause
            inmusculocontractural Ehlers-Danlos syndrome. Alternative splicing
            results in multiple transcript variants. A related pseudogene has
            been identified on chromosome 9, and a paralogous gene exists on
            chromosome 18. [provided by RefSeq, Apr 2016].
            
            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 :: SRR1803617.269212.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-213               AL050331.11        81614-81826
            214-735             AL050331.11        85889-86410
            736-1204            Z84488.1           65169-65637
            1205-1458           Z84488.1           92545-92798
            1459-1599           Z84488.1           96888-97028
            1600-1807           Z84488.1           99314-99521
            1808-11082          Z84488.1           101558-110832
FEATURES             Location/Qualifiers
     source          1..11082
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q22.1"
     gene            1..11082
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="dermatan sulfate epimerase"
                     /db_xref="GeneID:29940"
                     /db_xref="HGNC:HGNC:21144"
                     /db_xref="MIM:605942"
     exon            1..213
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            214..735
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            736..1204
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            1205..1458
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            1459..1599
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            1600..1807
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     CDS             1689..3566
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /EC_number="5.1.3.19"
                     /note="isoform f is encoded by transcript variant 15; DS
                     epimerase; chondroitin-glucuronate 5-epimerase; squamous
                     cell carcinoma antigen recognized by T-cells 2"
                     /codon_start=1
                     /product="dermatan-sulfate epimerase isoform f"
                     /protein_id="NP_001361449.1"
                     /db_xref="GeneID:29940"
                     /db_xref="HGNC:HGNC:21144"
                     /db_xref="MIM:605942"
                     /translation="MRNGSGNWLADQIRRNRVVEGPGTPSKGQRWCTLHTEFLWYDGS
                     LKSVPPPDFGTPTLHYFEDWGVVTYGSALPAEINRSFLSFKSGKLGGRAIYDIVHRNK
                     YKDWIKGWRNFNAGHEHPDQNSFTFAPNGVPFITEALYGPKYTFFNNVLMFSPAVSKS
                     CFSPWVGQVTEDCSSKWSKYKHDLAASCQGRVVAAEEKNGVVFIRGEGVGAYNPQLNL
                     KNVQRNLILLHPQLLLLVDQIHLGEESPLETAASFFHNVDVPFEETVVDGVHGAFIRQ
                     RDGLYKMYWMDDTGYSEKATFASVTYPRGYPYNGTNYVNVTMHLRSPITRAAYLFIGP
                     SIDVQSFTVHGDSQQLDVFIATSKHAYATYLWTGEATGQSAFAQVIADRHKILFDRNS
                     AIKSSIVPEVKDYAAIVEQNLQHFKPVFQLLEKQILSRVRNTASFRKTAERLLRFSDK
                     RQTEEAIDRIFAISQQQQQQSKSKKNRRAGKRYKFVDAVPDIFAQIEVNEKKIRQKAQ
                     ILAQKELPIDEDEEMKDLLDFADVTYEKHKNGGLIKGRFGQARMVTTTHSRAPSLSAS
                     YTRLFLILNIAIFFVMLAMQLTYFQRAQSLHGQRCLYAVLLIDSCILLWLYSSCSQSQ
                     C"
     exon            1808..11082
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4480..4485
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      4500
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="major polyA site"
     regulatory      4606..4611
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: TATAAA"
     polyA_site      4629
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
     regulatory      7461..7466
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      7482
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
     regulatory      11057..11062
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      11082
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
ORIGIN      
        1 ctctgcgcgg ttgactacgc ttatcaatcc atcgtattcc tttgtcttct tgtcacaaaa
       61 agaatttcgt cagtctggaa ggggagtttt acttacgtaa atggatgtag accagactca
      121 agcatgtaag aactgtgtta atgtggattt ctaagcctct gaatgaattt ctaaggcacc
      181 taacctattg tttctgaaaa tatttacttt aagggctgcc ctgaagggca gacaggttta
      241 ttgggcaaca gctgggaaaa tcagcggttg gacttggcca catgctccaa gaaggccaca
      301 cgtccttctt cttaatggca taggagttgg aggagccctt ggcagcattg atgagctcct
      361 ctgccaggca ctcagcaatg gtcttaatgt tccggaaggc agcctcacga gcacctgtgc
      421 acagcagcca gatggcctga ttcacacggc gaagtgggga cacgtccaca gcctgtcgtc
      481 tcacagtccc ggcgcaccca atgcgtgtgg agtcctcccg gggaccactg ttgatgatgg
      541 cgttcaccag gacctgcaga gggttctcgc ctgtgagcag gtgtatgacc tcgaaggcat
      601 gcttgacgat gcacacagtc atgagcttct tgccgttgtt gcagccgtgc atcatcatgg
      661 agttagtaag gcgctccaca atgggacact gagctttgtg gaagcatttg gcggcatacc
      721 accctgcact gtgaggatct ttcgaagatg gtttggctgc cttggagatt tggagatctg
      781 atgccacgat gaggactcac acacgggggg ctcccagtgt gtttttcata tatttgcttt
      841 gctttgtgtc agcctacatc accgacgaga acccagaagt tatgattccc ttcaccaatg
      901 ccaactacga cagccatccc atgctgtact tctccagggc agaagtggcg gagctgcagc
      961 tcagggctgc cagctcgcac gagcacattg cagcccgcct cacggaggct gtgcacacga
     1021 tgctgtccag ccccttggaa tacctccctc cctgggatcc caaggactac agtgcccgct
     1081 ggaatgaaat ttttggaaac aacttgggtg ccttggcaat gttctgtgtg ctgtatcctg
     1141 agaacattga agcccgagac atggccaaag actacatgga gaggatggca gcgcagccta
     1201 gttggttggt gaaagatgct ccttgggatg aggtcccgct tgctcactcc ctggttggtt
     1261 ttgccactgc ttatgacttc ttgtacaact acctgagcaa gacacaacag gagaagtttc
     1321 ttgaagtgat tgccaatgcc tcagggtata tgtatgaaac ttcatacagg agaggatggg
     1381 gatttcaata cctgcacaat catcagccca ccaactgtat ggctttgctc acgggaagcc
     1441 tagtcctgat gaatcaaggc tttagtcatt gcttccatgt gttttcatcc ttcaggatat
     1501 cttcaagaag cctacttatg gaccaaacaa gttctgacca tcatggagaa atctctggtc
     1561 ttgctcaggg aggtgacgga tggctccctc tatgaaggag gtttcaaagg actgtggcta
     1621 ttgcggactc aaattacaac tggttttatg gtccagaaag ccaattagtg ttccttgata
     1681 aatttgtcat gcgtaatggc agtggtaact ggctagctga ccaaatcaga aggaaccgtg
     1741 tggtggaagg tccaggaaca ccatccaaag ggcagcgctg gtgcactctg cacacagaat
     1801 ttctctggta tgatggcagc ttgaaatcgg ttcctcctcc agactttggc acccctacac
     1861 tgcattattt tgaagactgg ggtgtcgtga cttatggaag tgcactacct gcagaaatca
     1921 atagatcttt cctttccttc aagtctggaa aactgggggg acgtgcaata tatgacattg
     1981 tccacagaaa caaatacaaa gattggatca aaggatggag aaattttaat gcagggcatg
     2041 aacatcctga tcaaaactca tttacttttg ctcccaatgg tgtgcctttc attactgagg
     2101 ctctgtacgg gccaaagtac accttcttca acaatgtttt gatgttttcc ccagctgtgt
     2161 caaagagctg cttttctccc tgggtgggtc aggtcacaga agactgctca tcaaaatggt
     2221 ctaaatacaa gcatgacctg gcagctagtt gtcaggggag ggtggttgca gcagaggaga
     2281 aaaatggggt ggttttcatc cgaggagaag gtgtgggagc ttataacccc cagctcaacc
     2341 tgaagaatgt tcagaggaat ctcatcctcc tacatccaca gctgcttctc cttgtagacc
     2401 aaatacacct gggagaggag agtcccttgg agacagcagc gagcttcttc cataatgtgg
     2461 atgttccttt tgaggagact gtggtagatg gtgtccatgg ggctttcatc aggcagagag
     2521 atggtctcta taaaatgtac tggatggacg atactggcta cagcgagaaa gcaacctttg
     2581 cctcagtgac atatcctcgg ggctatccct acaatgggac aaactatgtg aatgtcacca
     2641 tgcacctccg aagtcccatc accagggcag cttacctctt catagggcca tctatagatg
     2701 ttcagagctt cactgtccac ggagactctc agcaactgga tgtgttcata gccaccagca
     2761 aacatgccta cgccacatac ctgtggacag gtgaggccac aggacagtct gcctttgcac
     2821 aggtcattgc tgatcgtcac aaaattctgt ttgaccggaa ttcagccatc aagagcagca
     2881 ttgtccctga ggtgaaggac tatgctgcta ttgtggaaca gaacttgcag cattttaaac
     2941 cagtgtttca gctgctggag aagcagatac tgtcccgagt ccggaacaca gctagcttta
     3001 ggaagactgc tgaacgcctg ctgagatttt cagataagag acagactgag gaggccattg
     3061 acaggatttt tgccatatca cagcaacagc agcagcaaag caagtcaaag aaaaaccgaa
     3121 gggcaggcaa acgctataaa tttgtggatg ctgtccctga tatttttgca cagattgaag
     3181 tcaatgagaa aaagattaga cagaaagctc agattttggc acagaaagaa ctacccatag
     3241 atgaagatga agaaatgaaa gaccttttag attttgcaga tgtaacatac gagaaacata
     3301 aaaatggggg cttgattaaa ggccggtttg gacaggcacg gatggtgaca actacacaca
     3361 gcagggcccc atcactgtct gcttcctata ccaggttgtt cctgattctg aacattgcta
     3421 ttttctttgt catgttggca atgcaactga cttatttcca gagggcccag agcctacatg
     3481 gccaaagatg tctttatgca gttcttctca tagatagctg tattttatta tggttgtact
     3541 cttcttgttc ccaatcacag tgttagcact gaagctataa attacctggt cattttgtga
     3601 tcacaagagt ctatgcaaaa aaaaaaattt ctttacccca gattatcaga tttttttccc
     3661 tcagattcat tttaacaaat taagggaaga tattttgaca caagaaagca ggaacgtgga
     3721 gaaattggag caggaaaaga aattatcaaa gcaatagaaa tagcttggtg gtcctatggt
     3781 gtttttggaa gtatttggca ttgctaattg agcagtccat atagtactac ttttagaaga
     3841 aacaaaaagt ctatttttta aagtaatgtt ttttcttatg agaaaaaggt ttagatagaa
     3901 ttgggtttta ttaatattaa tttaatgcta ttagcaattt ccatatacta tattgtggaa
     3961 aagactgaag aatacaattc tgagaaatat aaaaaaattt taatggtata ctcatgttga
     4021 aagataaatg ttgctaagtc ctggtatgat ggtgtgagct tccttgggga agtacttctt
     4081 gagttatgta actaacagga tgttttacta cagatctgga tggctattca gataacatgg
     4141 caaaaaatga tagcagaaga tcattaaaaa cttaaaatat attttattag aaaacattta
     4201 tctatgaatg aatatttcct tgatgctggt ctctgcacac atatgcttgg ttacttgcat
     4261 gcattcattg gttgttcaat aagtgagatg attacagata atactgtatt ttccttatat
     4321 ggaaaaccgt tatagaccca ataacaacta aacctttcaa aagaaaatat tttctattat
     4381 gaatgttgat tttcatacca aagaagatgg agagtctaaa atttggatat gattcttatg
     4441 tttttttaat agaaaacctt cttcaagttt attttcctaa ataaacatca taattgtgaa
     4501 ttttctctag tattcttctt ctttgttcca ttatattcaa aatgcattaa cattttccaa
     4561 aatttttgaa gagagatctt tatttggacg tgtattcatt aaatatataa agtagtgttt
     4621 gaatcaaaag aagtattttc tctgcttatt aaccttaatt gttgtttaag catattttaa
     4681 atatttaaaa caatagccaa ttctgatatt taagtagcac ccaactttta aaagcataaa
     4741 attttcaatc aactcctcag aaggtaacag cagcatagaa tactagaaaa ataatccata
     4801 gtttctactt gagcataaga aaatgatata cttaaaagga acttaataaa ttatcataca
     4861 ttcagcatat ttgagtcata tatttctcct ttgaaacaaa atatgttcag ctcaaatttt
     4921 acagtaagga cacactcact gatttatagg tgtaaagtaa caacagtaac ctttcctctt
     4981 acttgctctt ttagttcaca gcaataccag tatgtaacca aaagacaagc tagagaaact
     5041 tttaagtacc tttctgcagt tctaatttga accttcttgc ataaagaaaa cacaagtttg
     5101 acttttaact gtgcttcact tattatgctt ggaatctaga aaacgacttc tgaggaagta
     5161 atttttttcc cctctcatgg aaagtctcta gggaggatgt cattacacac tgtttaaaag
     5221 aataatgttt tcaaaagaat aatgcttccg tttgtcctgc atggatgctc ttactaggat
     5281 ttaaacttgc tttatgtgac agattctcca tttacttaac ctcactcaac attcctctct
     5341 tttactcttt ctcactcaaa aggatgaact gtctgaaatg atcaaaagga aattttgaaa
     5401 gaaaaaaaaa aggaaaatta ttctttgagg ttaccaagca aacctgatct cagatccaaa
     5461 ctgagacata ctttctaaca gagatgaaaa gtgcaagtga gtgccaaact cgcttttctt
     5521 ttgttttcat taggttaagg cttgacaata cgttagtcgc cacagcatga tccagtgtaa
     5581 catattagtt cattttaaag tagtcttttt aaaatacgca tctttaaaac aaaatgaatt
     5641 aaaattatgt gttttttttt tttcttctaa tgaacctggt atttatttcc ttaaaaagaa
     5701 acttcctcag gcagtgactt aagtggttaa gtgaaaaaaa aaaatgctga aacaaatcac
     5761 ccctcttcat aatgaaacat gtttttttta atcagggata gtgcatattt gagtaaaact
     5821 agggaacttt ttgtaacttg aaaacaaagc aatgttaaat ctcccttgaa actgagtaat
     5881 cagttatgga atctgtttca atgctgctca ctatgacagg aatgtttcaa gttcatttga
     5941 taatatgtga gctgttgttc aggggattgg caggactctt ggtcctagcc ttaaagaaaa
     6001 tttgagaatc actagcatac agagcttgtc agtgcagtaa aagtggtata ttcctgggaa
     6061 gctgaggtgg gagtattgcc tgagcttagg agttctgtgc tgcagtgagc tatgactgtg
     6121 ccactgcact ccagccttgg agacagagtg agaccgtgtt tctctctttt tttttttttt
     6181 aagtatattc ccttgtttat aactgattag cttatttcag ttgatggtag atgagaccta
     6241 tggtggtgga tgagacccag aattttcaga gagaacattc ttttgacaac attgttttaa
     6301 tcgtcaaagt caggtggaag accgtgttct ggaactattt taattgttaa aatgtatcac
     6361 ctaagataat gaattcttcc acaaatattt tagtcatagt ttttaagtac cacgtattct
     6421 aaggttatca gaaaatatgt cttaacagaa tgttttgcat actgaataat ttgtttttga
     6481 aaaggaaaat ttacatttga cttactcagt ttttaaaaaa ttatttttat ttctagagac
     6541 acggtccttt ctgcatcacc caggctgaag tgtagtggcg tgatcgtagc tcactgcagc
     6601 cgcaaacttc ccatcttaag cgattcttct gcctcagcct tccaaagtac tgggattaga
     6661 ggcataggtc atcatgcccg gccaagttaa aaaaattttt gatagttcac aaaccactca
     6721 caaaagaatc tgaaatttct ccaagtgtta agagaaagca agctatgaaa tgctatattt
     6781 gtaggcttaa aagtaaatta gtgtgttttc ttaaaaatct aaaccaagat taaaatgaat
     6841 atagtcatag gtatgagggg catgtaattt atcttccgac tggagatacc tttgagagtt
     6901 aaaggaggag caattaattg ttattccagg acaacagata taaatcgaga ttatactagg
     6961 tgaactggga catatggtca tctttgtcat agcttaattc aggaaaaaag gagttaggga
     7021 agtctgaagg tctaactcaa agtttgatgc tttttaagca agtttaggga acttgagatg
     7081 acctgattga gacccctaaa tctacagatg aggaaagcaa gcctcaagca aggggggcct
     7141 gatcctttcc ctgttcgctg tgtattccct gtctgtggca aagcccattg ccttgattct
     7201 cttctcttta ctttcatgtt gagaagtagt ttctttctgc agtttattta atttactggc
     7261 aaaatgacgt attttttttt cagcaatgtt tcagctagat atttgcttta tgcatgtaat
     7321 gtcaatgaag tactcataag ttttcaagaa atgactgata taaatcatgt gttccactac
     7381 atagtctaaa tatttagtat ttggtcatct attttaatat gttcaaattc tgttaaacaa
     7441 gacatagtca ctatgtgaag aataaaaata gacaaagttg cattatgact tttcttcttg
     7501 catatacagt ttccctcttg gttttgggat ttttttaatt gaagttttat ttggcataaa
     7561 ttatgaacat acatgattga aaaagtatag tactagaagc cttatttaaa aaacaaaaca
     7621 ataaattatc tgtcccttcc cctctcattc ttagtttgta cttcccagaa gtaaccaatt
     7681 tctaattctt ttggctgtta catatattgt gtacttgttt acaataaggt ctaaaactgc
     7741 ctactaatga agctttagct ctcttaccca ttctttatac ttattggaag ataataggtg
     7801 ctatggaagg aaaagtcagg gtaaggagac tgggaagagg aggccataat tttaaatgtg
     7861 gtgatcaggt taggctttat tgatgtctcc acttccattc tctgtgtcat tttgaaaatc
     7921 tatttgctgt taatttaatg gggttttagg aaggaactga aggaaattta tatattgagt
     7981 gcagtatgtt taaatggaag tcccacagca cttttcagtt gagttaacaa ataacgaatg
     8041 acaataacat gtttacagag catctactat atgccaagta ttgttttagg aactgaagat
     8101 atggtagaga ataggaataa taaaagctgg cccttgtata gtttatgttc tagtgggagc
     8161 aaataataac agtaatagtg caggatgtca agtagtggta agtactgtgg agaataaagc
     8221 aaggggaggg gatgtaaggt gatggtgaat tggtactgtc ccataaacag tggtttctga
     8281 tgtgattact tatgatcaga cacttgaaag aaataaggga atgaatcaca gggacatcta
     8341 agagagagga gcattccaga tagaacagca gttcgaaggc cctgagctca gtatgtgttt
     8401 ggtgtattta ggactaggag gccagtgtgg ctagagcaga gtgggggagg ggagggtgat
     8461 aggaatagga tcagatcata catgctctca cagactgcag caaagacttg gattatgagt
     8521 tggggagtca gttgcaatga actgagatgt ggctgactgc aggaggaata agtagtagga
     8581 agcgggtcca ggaggttgtt ttagccatgt taagtttaag atactttcta aaaatccaag
     8641 tggagatgta ccagcctgga atccaggggc aggctgtggc tgaagatgta attgttggtg
     8701 ccttcttaaa ggttaaacag aaatttacta gctgtgtgag aggagaagtg cattctgggt
     8761 aaatggaata gaataaagaa aaaagtacga aaaagcaaac ctggttcagg aattctccag
     8821 actggtggtg ttggcccaca gggtgtgtga tggagaatgg gtgaagatga aactgaaaag
     8881 gcaagcaggg aggctattgt gcaggacttt gtaggacatg ctaaggaatc tggactttat
     8941 tctgccatga ggctgctcaa ccatttttat gcctcagcat aactgagggc tacaacataa
     9001 cacccatcac tcaacaagca tggcagcgat tttcatggga taggaaatgt gtatgggagc
     9061 aaaagggaca tgggtgaggg gtgttgatga tgccacatat acctgtgtgt atgtgaaact
     9121 ttgaaaaatc cctgagatgg ctctgatatg ccccccatat tccatatgtt tactccctgg
     9181 ggtgaggtgg ggcagggagg gggtaccctc tgcttagaaa tcgctgcaag caatggcaag
     9241 ccattaaaga attttctttt taaataatca gatttgcatt ttagaaaggc aattttagct
     9301 tcagtgtaga gagtggaccc aatggggaag aggttaggag accatttcca tagtctgggt
     9361 agaagacaat tagctccttg aataagtctg gagagggaat gtttaactcc tagcccacag
     9421 gcaaaatgtg tggccaaagg aatgaatatt ttgtggaagt attgatcaga aagataatga
     9481 gtcaaggatc cctaatggta tatatgtctg agtcttattt aatataagaa gagcatggtt
     9541 gcctgccatg gctctgctgc cgtcaccctg gctatccctt aataagccca ggaaattgtt
     9601 caaatatttc tgccatttgt gttttcagct tgccttgttc agggacttca catagaatgg
     9661 tataactgga gtacagggtg tgtatgtagt ggcgggtgat agaaaattag actggaaaag
     9721 tagaccaggc tccagggcag gagggtctct tttcctcact ccatttaatt taaaaaagaa
     9781 atagtttcaa ttatataagc attgtgatta atgcaggcag ttggagtact ttctaaatca
     9841 gaaaagtaaa agtgctgctc cttctgcata tctctagaaa tttgttatgg ggaagtcttt
     9901 atcaaagaat gtccctatga tttcagtaga atttcttaag aaaagagctt ctaaaaacat
     9961 tcagtcagcc cagcacattc caaattaaat aatgagaagt gtgtttagta tttatttagg
    10021 aattcttttc tgaacaaaaa aacgttttca atggtctagg cacttccttt ttcttccaaa
    10081 gaaatggtaa taacaggaca ctagaagtac ctttctgtgt aaagcaaaca tcttgtcagt
    10141 tttccttact ttgtactttt cagtctctgc tgtttaccat ttttgtccag gatcagagac
    10201 ctccagtaaa ataaaaggaa tttctgttta ttgtctcctt gataatcttg atttctaaac
    10261 tcctttactc ctctcttgaa ggtatttgtt ttactgacaa aagaatggat ccaggtcatt
    10321 tagtagagtt ctgaagagaa ttcttagagc actctatata ttcaaacctc cgtatttttt
    10381 gatacaaaaa ggactgatga aagggagacg tgattctttt gaaagattaa ttcacagaat
    10441 tttttatcac agttgaaata tcaattgcaa taacaactga aaactgattg ctattactga
    10501 acactgccct taggtggctc actcttagaa gacacaaagt cactggacta caatccttta
    10561 gggcagggat tgtgtctctt gctcgttgta tatacatggt tcttacacag tgcctggcat
    10621 tcaaaaaatg cattcagaaa aatttggtat tcaaaaaatg cttgatgaat tgactgactg
    10681 cctgaatgaa taaataaatt ggtggattaa tgactgaatg gagtacagaa gactgtggtc
    10741 ccagaagacc ttaacattga gcttgctgca gactgaatgt ttgcctcctc tcaaaattaa
    10801 tatgttgaaa cctaatcctt aatgtgatag tattaggatg tggggccttt ggaaagtgat
    10861 taggttatga aggtggagcc ctcgtgaatg ggagtagtat ccttataaaa gataccccag
    10921 agaggtccct tgtcccttcc aacatgtgag gctacagtga aaagatggcc atctgtaaac
    10981 caggaagtga gtcctcacca gataccacat ctgttgtgct ttgatcttgg atttccctgt
    11041 ccccagaact gtggtaaata aatttctgtt gtttgtaagc ca
//
