LOCUS       NM_013352              10621 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens dermatan sulfate epimerase (DSE), transcript variant
            1, mRNA.
ACCESSION   NM_013352 XR_110215 XR_112918 XR_113912
VERSION     NM_013352.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 10621)
  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 10621)
  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 10621)
  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 10621)
  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 10621)
  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 10621)
  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 10621)
  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 10621)
  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 10621)
  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 10621)
  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 AW630671.1, AF098066.1,
            Z84488.1 and AL832471.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Feb 14, 2019 this sequence version replaced NM_013352.3.
            
            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].
            
            Transcript Variant: This variant (1) encodes isoform a. Variants 1,
            2, 3 and 4 all encode the same 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 :: SRR1660807.122639.1, AF098066.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000644252.3/ ENSP00000494147.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-79                AW630671.1         226-304
            80-2153             AF098066.1         1-2074
            2154-2154           Z84488.1           102365-102365
            2155-4034           AF098066.1         2076-3955
            4035-4051           AL832471.1         3207-3223
            4052-10621          Z84488.1           104263-110832
FEATURES             Location/Qualifiers
     source          1..10621
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q22.1"
     gene            1..10621
                     /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..175
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            176..644
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     CDS             229..3105
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /EC_number="5.1.3.19"
                     /note="isoform a precursor is encoded by transcript
                     variant 1; DS epimerase; chondroitin-glucuronate
                     5-epimerase; squamous cell carcinoma antigen recognized by
                     T-cells 2"
                     /codon_start=1
                     /product="dermatan-sulfate epimerase isoform a precursor"
                     /protein_id="NP_037484.1"
                     /db_xref="CCDS:CCDS5107.1"
                     /db_xref="GeneID:29940"
                     /db_xref="HGNC:HGNC:21144"
                     /db_xref="MIM:605942"
                     /translation="MRTHTRGAPSVFFIYLLCFVSAYITDENPEVMIPFTNANYDSHP
                     MLYFSRAEVAELQLRAASSHEHIAARLTEAVHTMLSSPLEYLPPWDPKDYSARWNEIF
                     GNNLGALAMFCVLYPENIEARDMAKDYMERMAAQPSWLVKDAPWDEVPLAHSLVGFAT
                     AYDFLYNYLSKTQQEKFLEVIANASGYMYETSYRRGWGFQYLHNHQPTNCMALLTGSL
                     VLMNQGYLQEAYLWTKQVLTIMEKSLVLLREVTDGSLYEGVAYGSYTTRSLFQYMFLV
                     QRHFNINHFGHPWLKQHFAFMYRTILPGFQRTVAIADSNYNWFYGPESQLVFLDKFVM
                     RNGSGNWLADQIRRNRVVEGPGTPSKGQRWCTLHTEFLWYDGSLKSVPPPDFGTPTLH
                     YFEDWGVVTYGSALPAEINRSFLSFKSGKLGGRAIYDIVHRNKYKDWIKGWRNFNAGH
                     EHPDQNSFTFAPNGVPFITEALYGPKYTFFNNVLMFSPAVSKSCFSPWVGQVTEDCSS
                     KWSKYKHDLAASCQGRVVAAEEKNGVVFIRGEGVGAYNPQLNLKNVQRNLILLHPQLL
                     LLVDQIHLGEESPLETAASFFHNVDVPFEETVVDGVHGAFIRQRDGLYKMYWMDDTGY
                     SEKATFASVTYPRGYPYNGTNYVNVTMHLRSPITRAAYLFIGPSIDVQSFTVHGDSQQ
                     LDVFIATSKHAYATYLWTGEATGQSAFAQVIADRHKILFDRNSAIKSSIVPEVKDYAA
                     IVEQNLQHFKPVFQLLEKQILSRVRNTASFRKTAERLLRFSDKRQTEEAIDRIFAISQ
                     QQQQQSKSKKNRRAGKRYKFVDAVPDIFAQIEVNEKKIRQKAQILAQKELPIDEDEEM
                     KDLLDFADVTYEKHKNGGLIKGRFGQARMVTTTHSRAPSLSASYTRLFLILNIAIFFV
                     MLAMQLTYFQRAQSLHGQRCLYAVLLIDSCILLWLYSSCSQSQC"
     exon            645..898
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            899..1138
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            1139..1346
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            1347..10621
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4019..4024
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      4039
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="major polyA site"
     regulatory      4145..4150
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: TATAAA"
     polyA_site      4168
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
     regulatory      7000..7005
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      7021
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
     regulatory      10596..10601
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      10621
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
ORIGIN      
        1 agtagcgtcg cccgaggctg cagcagcgca tcccggggca tggcgcggcg ggggcgcgga
       61 gggctcggtt cggagggggc cgggagcccg ggcgccctgg agtgaggagg accgggagct
      121 ggctctggag gctgcggagg cgacgccgga gagaacgaag cctcggctgg gagcggatct
      181 ttcgaagatg gtttggctgc cttggagatt tggagatctg atgccacgat gaggactcac
      241 acacgggggg ctcccagtgt gtttttcata tatttgcttt gctttgtgtc agcctacatc
      301 accgacgaga acccagaagt tatgattccc ttcaccaatg ccaactacga cagccatccc
      361 atgctgtact tctccagggc agaagtggcg gagctgcagc tcagggctgc cagctcgcac
      421 gagcacattg cagcccgcct cacggaggct gtgcacacga tgctgtccag ccccttggaa
      481 tacctccctc cctgggatcc caaggactac agtgcccgct ggaatgaaat ttttggaaac
      541 aacttgggtg ccttggcaat gttctgtgtg ctgtatcctg agaacattga agcccgagac
      601 atggccaaag actacatgga gaggatggca gcgcagccta gttggttggt gaaagatgct
      661 ccttgggatg aggtcccgct tgctcactcc ctggttggtt ttgccactgc ttatgacttc
      721 ttgtacaact acctgagcaa gacacaacag gagaagtttc ttgaagtgat tgccaatgcc
      781 tcagggtata tgtatgaaac ttcatacagg agaggatggg gatttcaata cctgcacaat
      841 catcagccca ccaactgtat ggctttgctc acgggaagcc tagtcctgat gaatcaagga
      901 tatcttcaag aagcctactt atggaccaaa caagttctga ccatcatgga gaaatctctg
      961 gtcttgctca gggaggtgac ggatggctcc ctctatgaag gagttgcgta tggcagctac
     1021 accactagat cactcttcca atacatgttt ctcgtccaga ggcacttcaa catcaaccac
     1081 tttggccatc cgtggcttaa acaacacttt gcatttatgt atagaaccat cctgccaggg
     1141 tttcaaagga ctgtggctat tgcggactca aattacaact ggttttatgg tccagaaagc
     1201 caattagtgt tccttgataa atttgtcatg cgtaatggca gtggtaactg gctagctgac
     1261 caaatcagaa ggaaccgtgt ggtggaaggt ccaggaacac catccaaagg gcagcgctgg
     1321 tgcactctgc acacagaatt tctctggtat gatggcagct tgaaatcggt tcctcctcca
     1381 gactttggca cccctacact gcattatttt gaagactggg gtgtcgtgac ttatggaagt
     1441 gcactacctg cagaaatcaa tagatctttc ctttccttca agtctggaaa actgggggga
     1501 cgtgcaatat atgacattgt ccacagaaac aaatacaaag attggatcaa aggatggaga
     1561 aattttaatg cagggcatga acatcctgat caaaactcat ttacttttgc tcccaatggt
     1621 gtgcctttca ttactgaggc tctgtacggg ccaaagtaca ccttcttcaa caatgttttg
     1681 atgttttccc cagctgtgtc aaagagctgc ttttctccct gggtgggtca ggtcacagaa
     1741 gactgctcat caaaatggtc taaatacaag catgacctgg cagctagttg tcaggggagg
     1801 gtggttgcag cagaggagaa aaatggggtg gttttcatcc gaggagaagg tgtgggagct
     1861 tataaccccc agctcaacct gaagaatgtt cagaggaatc tcatcctcct acatccacag
     1921 ctgcttctcc ttgtagacca aatacacctg ggagaggaga gtcccttgga gacagcagcg
     1981 agcttcttcc ataatgtgga tgttcctttt gaggagactg tggtagatgg tgtccatggg
     2041 gctttcatca ggcagagaga tggtctctat aaaatgtact ggatggacga tactggctac
     2101 agcgagaaag caacctttgc ctcagtgaca tatcctcggg gctatcccta caatgggaca
     2161 aactatgtga atgtcaccat gcacctccga agtcccatca ccagggcagc ttacctcttc
     2221 atagggccat ctatagatgt tcagagcttc actgtccacg gagactctca gcaactggat
     2281 gtgttcatag ccaccagcaa acatgcctac gccacatacc tgtggacagg tgaggccaca
     2341 ggacagtctg cctttgcaca ggtcattgct gatcgtcaca aaattctgtt tgaccggaat
     2401 tcagccatca agagcagcat tgtccctgag gtgaaggact atgctgctat tgtggaacag
     2461 aacttgcagc attttaaacc agtgtttcag ctgctggaga agcagatact gtcccgagtc
     2521 cggaacacag ctagctttag gaagactgct gaacgcctgc tgagattttc agataagaga
     2581 cagactgagg aggccattga caggattttt gccatatcac agcaacagca gcagcaaagc
     2641 aagtcaaaga aaaaccgaag ggcaggcaaa cgctataaat ttgtggatgc tgtccctgat
     2701 atttttgcac agattgaagt caatgagaaa aagattagac agaaagctca gattttggca
     2761 cagaaagaac tacccataga tgaagatgaa gaaatgaaag accttttaga ttttgcagat
     2821 gtaacatacg agaaacataa aaatgggggc ttgattaaag gccggtttgg acaggcacgg
     2881 atggtgacaa ctacacacag cagggcccca tcactgtctg cttcctatac caggttgttc
     2941 ctgattctga acattgctat tttctttgtc atgttggcaa tgcaactgac ttatttccag
     3001 agggcccaga gcctacatgg ccaaagatgt ctttatgcag ttcttctcat agatagctgt
     3061 attttattat ggttgtactc ttcttgttcc caatcacagt gttagcactg aagctataaa
     3121 ttacctggtc attttgtgat cacaagagtc tatgcaaaaa aaaaaatttc tttaccccag
     3181 attatcagat ttttttccct cagattcatt ttaacaaatt aagggaagat attttgacac
     3241 aagaaagcag gaacgtggag aaattggagc aggaaaagaa attatcaaag caatagaaat
     3301 agcttggtgg tcctatggtg tttttggaag tatttggcat tgctaattga gcagtccata
     3361 tagtactact tttagaagaa acaaaaagtc tattttttaa agtaatgttt tttcttatga
     3421 gaaaaaggtt tagatagaat tgggttttat taatattaat ttaatgctat tagcaatttc
     3481 catatactat attgtggaaa agactgaaga atacaattct gagaaatata aaaaaatttt
     3541 aatggtatac tcatgttgaa agataaatgt tgctaagtcc tggtatgatg gtgtgagctt
     3601 ccttggggaa gtacttcttg agttatgtaa ctaacaggat gttttactac agatctggat
     3661 ggctattcag ataacatggc aaaaaatgat agcagaagat cattaaaaac ttaaaatata
     3721 ttttattaga aaacatttat ctatgaatga atatttcctt gatgctggtc tctgcacaca
     3781 tatgcttggt tacttgcatg cattcattgg ttgttcaata agtgagatga ttacagataa
     3841 tactgtattt tccttatatg gaaaaccgtt atagacccaa taacaactaa acctttcaaa
     3901 agaaaatatt ttctattatg aatgttgatt ttcataccaa agaagatgga gagtctaaaa
     3961 tttggatatg attcttatgt ttttttaata gaaaaccttc ttcaagttta ttttcctaaa
     4021 taaacatcat aattgtgaat tttctctagt attcttcttc tttgttccat tatattcaaa
     4081 atgcattaac attttccaaa atttttgaag agagatcttt atttggacgt gtattcatta
     4141 aatatataaa gtagtgtttg aatcaaaaga agtattttct ctgcttatta accttaattg
     4201 ttgtttaagc atattttaaa tatttaaaac aatagccaat tctgatattt aagtagcacc
     4261 caacttttaa aagcataaaa ttttcaatca actcctcaga aggtaacagc agcatagaat
     4321 actagaaaaa taatccatag tttctacttg agcataagaa aatgatatac ttaaaaggaa
     4381 cttaataaat tatcatacat tcagcatatt tgagtcatat atttctcctt tgaaacaaaa
     4441 tatgttcagc tcaaatttta cagtaaggac acactcactg atttataggt gtaaagtaac
     4501 aacagtaacc tttcctctta cttgctcttt tagttcacag caataccagt atgtaaccaa
     4561 aagacaagct agagaaactt ttaagtacct ttctgcagtt ctaatttgaa ccttcttgca
     4621 taaagaaaac acaagtttga cttttaactg tgcttcactt attatgcttg gaatctagaa
     4681 aacgacttct gaggaagtaa tttttttccc ctctcatgga aagtctctag ggaggatgtc
     4741 attacacact gtttaaaaga ataatgtttt caaaagaata atgcttccgt ttgtcctgca
     4801 tggatgctct tactaggatt taaacttgct ttatgtgaca gattctccat ttacttaacc
     4861 tcactcaaca ttcctctctt ttactctttc tcactcaaaa ggatgaactg tctgaaatga
     4921 tcaaaaggaa attttgaaag aaaaaaaaaa ggaaaattat tctttgaggt taccaagcaa
     4981 acctgatctc agatccaaac tgagacatac tttctaacag agatgaaaag tgcaagtgag
     5041 tgccaaactc gcttttcttt tgttttcatt aggttaaggc ttgacaatac gttagtcgcc
     5101 acagcatgat ccagtgtaac atattagttc attttaaagt agtcttttta aaatacgcat
     5161 ctttaaaaca aaatgaatta aaattatgtg tttttttttt ttcttctaat gaacctggta
     5221 tttatttcct taaaaagaaa cttcctcagg cagtgactta agtggttaag tgaaaaaaaa
     5281 aaatgctgaa acaaatcacc cctcttcata atgaaacatg ttttttttaa tcagggatag
     5341 tgcatatttg agtaaaacta gggaactttt tgtaacttga aaacaaagca atgttaaatc
     5401 tcccttgaaa ctgagtaatc agttatggaa tctgtttcaa tgctgctcac tatgacagga
     5461 atgtttcaag ttcatttgat aatatgtgag ctgttgttca ggggattggc aggactcttg
     5521 gtcctagcct taaagaaaat ttgagaatca ctagcataca gagcttgtca gtgcagtaaa
     5581 agtggtatat tcctgggaag ctgaggtggg agtattgcct gagcttagga gttctgtgct
     5641 gcagtgagct atgactgtgc cactgcactc cagccttgga gacagagtga gaccgtgttt
     5701 ctctcttttt ttttttttta agtatattcc cttgtttata actgattagc ttatttcagt
     5761 tgatggtaga tgagacctat ggtggtggat gagacccaga attttcagag agaacattct
     5821 tttgacaaca ttgttttaat cgtcaaagtc aggtggaaga ccgtgttctg gaactatttt
     5881 aattgttaaa atgtatcacc taagataatg aattcttcca caaatatttt agtcatagtt
     5941 tttaagtacc acgtattcta aggttatcag aaaatatgtc ttaacagaat gttttgcata
     6001 ctgaataatt tgtttttgaa aaggaaaatt tacatttgac ttactcagtt tttaaaaaat
     6061 tatttttatt tctagagaca cggtcctttc tgcatcaccc aggctgaagt gtagtggcgt
     6121 gatcgtagct cactgcagcc gcaaacttcc catcttaagc gattcttctg cctcagcctt
     6181 ccaaagtact gggattagag gcataggtca tcatgcccgg ccaagttaaa aaaatttttg
     6241 atagttcaca aaccactcac aaaagaatct gaaatttctc caagtgttaa gagaaagcaa
     6301 gctatgaaat gctatatttg taggcttaaa agtaaattag tgtgttttct taaaaatcta
     6361 aaccaagatt aaaatgaata tagtcatagg tatgaggggc atgtaattta tcttccgact
     6421 ggagatacct ttgagagtta aaggaggagc aattaattgt tattccagga caacagatat
     6481 aaatcgagat tatactaggt gaactgggac atatggtcat ctttgtcata gcttaattca
     6541 ggaaaaaagg agttagggaa gtctgaaggt ctaactcaaa gtttgatgct ttttaagcaa
     6601 gtttagggaa cttgagatga cctgattgag acccctaaat ctacagatga ggaaagcaag
     6661 cctcaagcaa ggggggcctg atcctttccc tgttcgctgt gtattccctg tctgtggcaa
     6721 agcccattgc cttgattctc ttctctttac tttcatgttg agaagtagtt tctttctgca
     6781 gtttatttaa tttactggca aaatgacgta tttttttttc agcaatgttt cagctagata
     6841 tttgctttat gcatgtaatg tcaatgaagt actcataagt tttcaagaaa tgactgatat
     6901 aaatcatgtg ttccactaca tagtctaaat atttagtatt tggtcatcta ttttaatatg
     6961 ttcaaattct gttaaacaag acatagtcac tatgtgaaga ataaaaatag acaaagttgc
     7021 attatgactt ttcttcttgc atatacagtt tccctcttgg ttttgggatt tttttaattg
     7081 aagttttatt tggcataaat tatgaacata catgattgaa aaagtatagt actagaagcc
     7141 ttatttaaaa aacaaaacaa taaattatct gtcccttccc ctctcattct tagtttgtac
     7201 ttcccagaag taaccaattt ctaattcttt tggctgttac atatattgtg tacttgttta
     7261 caataaggtc taaaactgcc tactaatgaa gctttagctc tcttacccat tctttatact
     7321 tattggaaga taataggtgc tatggaagga aaagtcaggg taaggagact gggaagagga
     7381 ggccataatt ttaaatgtgg tgatcaggtt aggctttatt gatgtctcca cttccattct
     7441 ctgtgtcatt ttgaaaatct atttgctgtt aatttaatgg ggttttagga aggaactgaa
     7501 ggaaatttat atattgagtg cagtatgttt aaatggaagt cccacagcac ttttcagttg
     7561 agttaacaaa taacgaatga caataacatg tttacagagc atctactata tgccaagtat
     7621 tgttttagga actgaagata tggtagagaa taggaataat aaaagctggc ccttgtatag
     7681 tttatgttct agtgggagca aataataaca gtaatagtgc aggatgtcaa gtagtggtaa
     7741 gtactgtgga gaataaagca aggggagggg atgtaaggtg atggtgaatt ggtactgtcc
     7801 cataaacagt ggtttctgat gtgattactt atgatcagac acttgaaaga aataagggaa
     7861 tgaatcacag ggacatctaa gagagaggag cattccagat agaacagcag ttcgaaggcc
     7921 ctgagctcag tatgtgtttg gtgtatttag gactaggagg ccagtgtggc tagagcagag
     7981 tgggggaggg gagggtgata ggaataggat cagatcatac atgctctcac agactgcagc
     8041 aaagacttgg attatgagtt ggggagtcag ttgcaatgaa ctgagatgtg gctgactgca
     8101 ggaggaataa gtagtaggaa gcgggtccag gaggttgttt tagccatgtt aagtttaaga
     8161 tactttctaa aaatccaagt ggagatgtac cagcctggaa tccaggggca ggctgtggct
     8221 gaagatgtaa ttgttggtgc cttcttaaag gttaaacaga aatttactag ctgtgtgaga
     8281 ggagaagtgc attctgggta aatggaatag aataaagaaa aaagtacgaa aaagcaaacc
     8341 tggttcagga attctccaga ctggtggtgt tggcccacag ggtgtgtgat ggagaatggg
     8401 tgaagatgaa actgaaaagg caagcaggga ggctattgtg caggactttg taggacatgc
     8461 taaggaatct ggactttatt ctgccatgag gctgctcaac catttttatg cctcagcata
     8521 actgagggct acaacataac acccatcact caacaagcat ggcagcgatt ttcatgggat
     8581 aggaaatgtg tatgggagca aaagggacat gggtgagggg tgttgatgat gccacatata
     8641 cctgtgtgta tgtgaaactt tgaaaaatcc ctgagatggc tctgatatgc cccccatatt
     8701 ccatatgttt actccctggg gtgaggtggg gcagggaggg ggtaccctct gcttagaaat
     8761 cgctgcaagc aatggcaagc cattaaagaa ttttcttttt aaataatcag atttgcattt
     8821 tagaaaggca attttagctt cagtgtagag agtggaccca atggggaaga ggttaggaga
     8881 ccatttccat agtctgggta gaagacaatt agctccttga ataagtctgg agagggaatg
     8941 tttaactcct agcccacagg caaaatgtgt ggccaaagga atgaatattt tgtggaagta
     9001 ttgatcagaa agataatgag tcaaggatcc ctaatggtat atatgtctga gtcttattta
     9061 atataagaag agcatggttg cctgccatgg ctctgctgcc gtcaccctgg ctatccctta
     9121 ataagcccag gaaattgttc aaatatttct gccatttgtg ttttcagctt gccttgttca
     9181 gggacttcac atagaatggt ataactggag tacagggtgt gtatgtagtg gcgggtgata
     9241 gaaaattaga ctggaaaagt agaccaggct ccagggcagg agggtctctt ttcctcactc
     9301 catttaattt aaaaaagaaa tagtttcaat tatataagca ttgtgattaa tgcaggcagt
     9361 tggagtactt tctaaatcag aaaagtaaaa gtgctgctcc ttctgcatat ctctagaaat
     9421 ttgttatggg gaagtcttta tcaaagaatg tccctatgat ttcagtagaa tttcttaaga
     9481 aaagagcttc taaaaacatt cagtcagccc agcacattcc aaattaaata atgagaagtg
     9541 tgtttagtat ttatttagga attcttttct gaacaaaaaa acgttttcaa tggtctaggc
     9601 acttcctttt tcttccaaag aaatggtaat aacaggacac tagaagtacc tttctgtgta
     9661 aagcaaacat cttgtcagtt ttccttactt tgtacttttc agtctctgct gtttaccatt
     9721 tttgtccagg atcagagacc tccagtaaaa taaaaggaat ttctgtttat tgtctccttg
     9781 ataatcttga tttctaaact cctttactcc tctcttgaag gtatttgttt tactgacaaa
     9841 agaatggatc caggtcattt agtagagttc tgaagagaat tcttagagca ctctatatat
     9901 tcaaacctcc gtattttttg atacaaaaag gactgatgaa agggagacgt gattcttttg
     9961 aaagattaat tcacagaatt ttttatcaca gttgaaatat caattgcaat aacaactgaa
    10021 aactgattgc tattactgaa cactgccctt aggtggctca ctcttagaag acacaaagtc
    10081 actggactac aatcctttag ggcagggatt gtgtctcttg ctcgttgtat atacatggtt
    10141 cttacacagt gcctggcatt caaaaaatgc attcagaaaa atttggtatt caaaaaatgc
    10201 ttgatgaatt gactgactgc ctgaatgaat aaataaattg gtggattaat gactgaatgg
    10261 agtacagaag actgtggtcc cagaagacct taacattgag cttgctgcag actgaatgtt
    10321 tgcctcctct caaaattaat atgttgaaac ctaatcctta atgtgatagt attaggatgt
    10381 ggggcctttg gaaagtgatt aggttatgaa ggtggagccc tcgtgaatgg gagtagtatc
    10441 cttataaaag ataccccaga gaggtccctt gtcccttcca acatgtgagg ctacagtgaa
    10501 aagatggcca tctgtaaacc aggaagtgag tcctcaccag ataccacatc tgttgtgctt
    10561 tgatcttgga tttccctgtc cccagaactg tggtaaataa atttctgttg tttgtaagcc
    10621 a
//
