LOCUS       NM_001322939           10555 bp    mRNA    linear   PRI 06-APR-2024
DEFINITION  Homo sapiens dermatan sulfate epimerase (DSE), transcript variant
            5, mRNA.
ACCESSION   NM_001322939
VERSION     NM_001322939.2
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 10555)
  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 10555)
  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 10555)
  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 10555)
  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 10555)
  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 10555)
  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 10555)
  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 10555)
  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 10555)
  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 10555)
  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 Z84488.1.
            
            On Jun 2, 2019 this sequence version replaced NM_001322939.1.
            
            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].
            
            Transcript Variant: This variant (5) contains an alternate 5' exon
            and it thus differs in the 5' UTR and initiates translation at an
            alternate start codon, compared to variant 1. The encoded isoform
            (b) has a distinct N-terminus and is longer than isoform a.
            
            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 :: AK301513.1, SRR18074968.3196492.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-109               Z84488.1           35790-35898
            110-578             Z84488.1           65169-65637
            579-832             Z84488.1           92545-92798
            833-1072            Z84488.1           96925-97164
            1073-1280           Z84488.1           99314-99521
            1281-10555          Z84488.1           101558-110832
FEATURES             Location/Qualifiers
     source          1..10555
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q22.1"
     gene            1..10555
                     /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..109
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     CDS             106..3039
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /EC_number="5.1.3.19"
                     /note="isoform b is encoded by transcript variant 5; DS
                     epimerase; chondroitin-glucuronate 5-epimerase; squamous
                     cell carcinoma antigen recognized by T-cells 2"
                     /codon_start=1
                     /product="dermatan-sulfate epimerase isoform b"
                     /protein_id="NP_001309868.1"
                     /db_xref="GeneID:29940"
                     /db_xref="HGNC:HGNC:21144"
                     /db_xref="MIM:605942"
                     /translation="MGSFEDGLAALEIWRSDATMRTHTRGAPSVFFIYLLCFVSAYIT
                     DENPEVMIPFTNANYDSHPMLYFSRAEVAELQLRAASSHEHIAARLTEAVHTMLSSPL
                     EYLPPWDPKDYSARWNEIFGNNLGALAMFCVLYPENIEARDMAKDYMERMAAQPSWLV
                     KDAPWDEVPLAHSLVGFATAYDFLYNYLSKTQQEKFLEVIANASGYMYETSYRRGWGF
                     QYLHNHQPTNCMALLTGSLVLMNQGYLQEAYLWTKQVLTIMEKSLVLLREVTDGSLYE
                     GVAYGSYTTRSLFQYMFLVQRHFNINHFGHPWLKQHFAFMYRTILPGFQRTVAIADSN
                     YNWFYGPESQLVFLDKFVMRNGSGNWLADQIRRNRVVEGPGTPSKGQRWCTLHTEFLW
                     YDGSLKSVPPPDFGTPTLHYFEDWGVVTYGSALPAEINRSFLSFKSGKLGGRAIYDIV
                     HRNKYKDWIKGWRNFNAGHEHPDQNSFTFAPNGVPFITEALYGPKYTFFNNVLMFSPA
                     VSKSCFSPWVGQVTEDCSSKWSKYKHDLAASCQGRVVAAEEKNGVVFIRGEGVGAYNP
                     QLNLKNVQRNLILLHPQLLLLVDQIHLGEESPLETAASFFHNVDVPFEETVVDGVHGA
                     FIRQRDGLYKMYWMDDTGYSEKATFASVTYPRGYPYNGTNYVNVTMHLRSPITRAAYL
                     FIGPSIDVQSFTVHGDSQQLDVFIATSKHAYATYLWTGEATGQSAFAQVIADRHKILF
                     DRNSAIKSSIVPEVKDYAAIVEQNLQHFKPVFQLLEKQILSRVRNTASFRKTAERLLR
                     FSDKRQTEEAIDRIFAISQQQQQQSKSKKNRRAGKRYKFVDAVPDIFAQIEVNEKKIR
                     QKAQILAQKELPIDEDEEMKDLLDFADVTYEKHKNGGLIKGRFGQARMVTTTHSRAPS
                     LSASYTRLFLILNIAIFFVMLAMQLTYFQRAQSLHGQRCLYAVLLIDSCILLWLYSSC
                     SQSQC"
     exon            110..578
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            579..832
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            833..1072
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            1073..1280
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            1281..10555
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3953..3958
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      3973
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="major polyA site"
     regulatory      4079..4084
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: TATAAA"
     polyA_site      4102
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
     regulatory      6934..6939
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      6955
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
     regulatory      10530..10535
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      10555
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
ORIGIN      
        1 aaatagaagt gagaacctct gaggatagag gaattggatg gaggtgccct tcagaactca
       61 tggagaaaag cactgctccc agtaaaatat ctctcattct aatgaatggg atctttcgaa
      121 gatggtttgg ctgccttgga gatttggaga tctgatgcca cgatgaggac tcacacacgg
      181 ggggctccca gtgtgttttt catatatttg ctttgctttg tgtcagccta catcaccgac
      241 gagaacccag aagttatgat tcccttcacc aatgccaact acgacagcca tcccatgctg
      301 tacttctcca gggcagaagt ggcggagctg cagctcaggg ctgccagctc gcacgagcac
      361 attgcagccc gcctcacgga ggctgtgcac acgatgctgt ccagcccctt ggaatacctc
      421 cctccctggg atcccaagga ctacagtgcc cgctggaatg aaatttttgg aaacaacttg
      481 ggtgccttgg caatgttctg tgtgctgtat cctgagaaca ttgaagcccg agacatggcc
      541 aaagactaca tggagaggat ggcagcgcag cctagttggt tggtgaaaga tgctccttgg
      601 gatgaggtcc cgcttgctca ctccctggtt ggttttgcca ctgcttatga cttcttgtac
      661 aactacctga gcaagacaca acaggagaag tttcttgaag tgattgccaa tgcctcaggg
      721 tatatgtatg aaacttcata caggagagga tggggatttc aatacctgca caatcatcag
      781 cccaccaact gtatggcttt gctcacggga agcctagtcc tgatgaatca aggatatctt
      841 caagaagcct acttatggac caaacaagtt ctgaccatca tggagaaatc tctggtcttg
      901 ctcagggagg tgacggatgg ctccctctat gaaggagttg cgtatggcag ctacaccact
      961 agatcactct tccaatacat gtttctcgtc cagaggcact tcaacatcaa ccactttggc
     1021 catccgtggc ttaaacaaca ctttgcattt atgtatagaa ccatcctgcc agggtttcaa
     1081 aggactgtgg ctattgcgga ctcaaattac aactggtttt atggtccaga aagccaatta
     1141 gtgttccttg ataaatttgt catgcgtaat ggcagtggta actggctagc tgaccaaatc
     1201 agaaggaacc gtgtggtgga aggtccagga acaccatcca aagggcagcg ctggtgcact
     1261 ctgcacacag aatttctctg gtatgatggc agcttgaaat cggttcctcc tccagacttt
     1321 ggcaccccta cactgcatta ttttgaagac tggggtgtcg tgacttatgg aagtgcacta
     1381 cctgcagaaa tcaatagatc tttcctttcc ttcaagtctg gaaaactggg gggacgtgca
     1441 atatatgaca ttgtccacag aaacaaatac aaagattgga tcaaaggatg gagaaatttt
     1501 aatgcagggc atgaacatcc tgatcaaaac tcatttactt ttgctcccaa tggtgtgcct
     1561 ttcattactg aggctctgta cgggccaaag tacaccttct tcaacaatgt tttgatgttt
     1621 tccccagctg tgtcaaagag ctgcttttct ccctgggtgg gtcaggtcac agaagactgc
     1681 tcatcaaaat ggtctaaata caagcatgac ctggcagcta gttgtcaggg gagggtggtt
     1741 gcagcagagg agaaaaatgg ggtggttttc atccgaggag aaggtgtggg agcttataac
     1801 ccccagctca acctgaagaa tgttcagagg aatctcatcc tcctacatcc acagctgctt
     1861 ctccttgtag accaaataca cctgggagag gagagtccct tggagacagc agcgagcttc
     1921 ttccataatg tggatgttcc ttttgaggag actgtggtag atggtgtcca tggggctttc
     1981 atcaggcaga gagatggtct ctataaaatg tactggatgg acgatactgg ctacagcgag
     2041 aaagcaacct ttgcctcagt gacatatcct cggggctatc cctacaatgg gacaaactat
     2101 gtgaatgtca ccatgcacct ccgaagtccc atcaccaggg cagcttacct cttcataggg
     2161 ccatctatag atgttcagag cttcactgtc cacggagact ctcagcaact ggatgtgttc
     2221 atagccacca gcaaacatgc ctacgccaca tacctgtgga caggtgaggc cacaggacag
     2281 tctgcctttg cacaggtcat tgctgatcgt cacaaaattc tgtttgaccg gaattcagcc
     2341 atcaagagca gcattgtccc tgaggtgaag gactatgctg ctattgtgga acagaacttg
     2401 cagcatttta aaccagtgtt tcagctgctg gagaagcaga tactgtcccg agtccggaac
     2461 acagctagct ttaggaagac tgctgaacgc ctgctgagat tttcagataa gagacagact
     2521 gaggaggcca ttgacaggat ttttgccata tcacagcaac agcagcagca aagcaagtca
     2581 aagaaaaacc gaagggcagg caaacgctat aaatttgtgg atgctgtccc tgatattttt
     2641 gcacagattg aagtcaatga gaaaaagatt agacagaaag ctcagatttt ggcacagaaa
     2701 gaactaccca tagatgaaga tgaagaaatg aaagaccttt tagattttgc agatgtaaca
     2761 tacgagaaac ataaaaatgg gggcttgatt aaaggccggt ttggacaggc acggatggtg
     2821 acaactacac acagcagggc cccatcactg tctgcttcct ataccaggtt gttcctgatt
     2881 ctgaacattg ctattttctt tgtcatgttg gcaatgcaac tgacttattt ccagagggcc
     2941 cagagcctac atggccaaag atgtctttat gcagttcttc tcatagatag ctgtatttta
     3001 ttatggttgt actcttcttg ttcccaatca cagtgttagc actgaagcta taaattacct
     3061 ggtcattttg tgatcacaag agtctatgca aaaaaaaaaa tttctttacc ccagattatc
     3121 agattttttt ccctcagatt cattttaaca aattaaggga agatattttg acacaagaaa
     3181 gcaggaacgt ggagaaattg gagcaggaaa agaaattatc aaagcaatag aaatagcttg
     3241 gtggtcctat ggtgtttttg gaagtatttg gcattgctaa ttgagcagtc catatagtac
     3301 tacttttaga agaaacaaaa agtctatttt ttaaagtaat gttttttctt atgagaaaaa
     3361 ggtttagata gaattgggtt ttattaatat taatttaatg ctattagcaa tttccatata
     3421 ctatattgtg gaaaagactg aagaatacaa ttctgagaaa tataaaaaaa ttttaatggt
     3481 atactcatgt tgaaagataa atgttgctaa gtcctggtat gatggtgtga gcttccttgg
     3541 ggaagtactt cttgagttat gtaactaaca ggatgtttta ctacagatct ggatggctat
     3601 tcagataaca tggcaaaaaa tgatagcaga agatcattaa aaacttaaaa tatattttat
     3661 tagaaaacat ttatctatga atgaatattt ccttgatgct ggtctctgca cacatatgct
     3721 tggttacttg catgcattca ttggttgttc aataagtgag atgattacag ataatactgt
     3781 attttcctta tatggaaaac cgttatagac ccaataacaa ctaaaccttt caaaagaaaa
     3841 tattttctat tatgaatgtt gattttcata ccaaagaaga tggagagtct aaaatttgga
     3901 tatgattctt atgttttttt aatagaaaac cttcttcaag tttattttcc taaataaaca
     3961 tcataattgt gaattttctc tagtattctt cttctttgtt ccattatatt caaaatgcat
     4021 taacattttc caaaattttt gaagagagat ctttatttgg acgtgtattc attaaatata
     4081 taaagtagtg tttgaatcaa aagaagtatt ttctctgctt attaacctta attgttgttt
     4141 aagcatattt taaatattta aaacaatagc caattctgat atttaagtag cacccaactt
     4201 ttaaaagcat aaaattttca atcaactcct cagaaggtaa cagcagcata gaatactaga
     4261 aaaataatcc atagtttcta cttgagcata agaaaatgat atacttaaaa ggaacttaat
     4321 aaattatcat acattcagca tatttgagtc atatatttct cctttgaaac aaaatatgtt
     4381 cagctcaaat tttacagtaa ggacacactc actgatttat aggtgtaaag taacaacagt
     4441 aacctttcct cttacttgct cttttagttc acagcaatac cagtatgtaa ccaaaagaca
     4501 agctagagaa acttttaagt acctttctgc agttctaatt tgaaccttct tgcataaaga
     4561 aaacacaagt ttgactttta actgtgcttc acttattatg cttggaatct agaaaacgac
     4621 ttctgaggaa gtaatttttt tcccctctca tggaaagtct ctagggagga tgtcattaca
     4681 cactgtttaa aagaataatg ttttcaaaag aataatgctt ccgtttgtcc tgcatggatg
     4741 ctcttactag gatttaaact tgctttatgt gacagattct ccatttactt aacctcactc
     4801 aacattcctc tcttttactc tttctcactc aaaaggatga actgtctgaa atgatcaaaa
     4861 ggaaattttg aaagaaaaaa aaaaggaaaa ttattctttg aggttaccaa gcaaacctga
     4921 tctcagatcc aaactgagac atactttcta acagagatga aaagtgcaag tgagtgccaa
     4981 actcgctttt cttttgtttt cattaggtta aggcttgaca atacgttagt cgccacagca
     5041 tgatccagtg taacatatta gttcatttta aagtagtctt tttaaaatac gcatctttaa
     5101 aacaaaatga attaaaatta tgtgtttttt ttttttcttc taatgaacct ggtatttatt
     5161 tccttaaaaa gaaacttcct caggcagtga cttaagtggt taagtgaaaa aaaaaaatgc
     5221 tgaaacaaat cacccctctt cataatgaaa catgtttttt ttaatcaggg atagtgcata
     5281 tttgagtaaa actagggaac tttttgtaac ttgaaaacaa agcaatgtta aatctccctt
     5341 gaaactgagt aatcagttat ggaatctgtt tcaatgctgc tcactatgac aggaatgttt
     5401 caagttcatt tgataatatg tgagctgttg ttcaggggat tggcaggact cttggtccta
     5461 gccttaaaga aaatttgaga atcactagca tacagagctt gtcagtgcag taaaagtggt
     5521 atattcctgg gaagctgagg tgggagtatt gcctgagctt aggagttctg tgctgcagtg
     5581 agctatgact gtgccactgc actccagcct tggagacaga gtgagaccgt gtttctctct
     5641 tttttttttt tttaagtata ttcccttgtt tataactgat tagcttattt cagttgatgg
     5701 tagatgagac ctatggtggt ggatgagacc cagaattttc agagagaaca ttcttttgac
     5761 aacattgttt taatcgtcaa agtcaggtgg aagaccgtgt tctggaacta ttttaattgt
     5821 taaaatgtat cacctaagat aatgaattct tccacaaata ttttagtcat agtttttaag
     5881 taccacgtat tctaaggtta tcagaaaata tgtcttaaca gaatgttttg catactgaat
     5941 aatttgtttt tgaaaaggaa aatttacatt tgacttactc agtttttaaa aaattatttt
     6001 tatttctaga gacacggtcc tttctgcatc acccaggctg aagtgtagtg gcgtgatcgt
     6061 agctcactgc agccgcaaac ttcccatctt aagcgattct tctgcctcag ccttccaaag
     6121 tactgggatt agaggcatag gtcatcatgc ccggccaagt taaaaaaatt tttgatagtt
     6181 cacaaaccac tcacaaaaga atctgaaatt tctccaagtg ttaagagaaa gcaagctatg
     6241 aaatgctata tttgtaggct taaaagtaaa ttagtgtgtt ttcttaaaaa tctaaaccaa
     6301 gattaaaatg aatatagtca taggtatgag gggcatgtaa tttatcttcc gactggagat
     6361 acctttgaga gttaaaggag gagcaattaa ttgttattcc aggacaacag atataaatcg
     6421 agattatact aggtgaactg ggacatatgg tcatctttgt catagcttaa ttcaggaaaa
     6481 aaggagttag ggaagtctga aggtctaact caaagtttga tgctttttaa gcaagtttag
     6541 ggaacttgag atgacctgat tgagacccct aaatctacag atgaggaaag caagcctcaa
     6601 gcaagggggg cctgatcctt tccctgttcg ctgtgtattc cctgtctgtg gcaaagccca
     6661 ttgccttgat tctcttctct ttactttcat gttgagaagt agtttctttc tgcagtttat
     6721 ttaatttact ggcaaaatga cgtatttttt tttcagcaat gtttcagcta gatatttgct
     6781 ttatgcatgt aatgtcaatg aagtactcat aagttttcaa gaaatgactg atataaatca
     6841 tgtgttccac tacatagtct aaatatttag tatttggtca tctattttaa tatgttcaaa
     6901 ttctgttaaa caagacatag tcactatgtg aagaataaaa atagacaaag ttgcattatg
     6961 acttttcttc ttgcatatac agtttccctc ttggttttgg gattttttta attgaagttt
     7021 tatttggcat aaattatgaa catacatgat tgaaaaagta tagtactaga agccttattt
     7081 aaaaaacaaa acaataaatt atctgtccct tcccctctca ttcttagttt gtacttccca
     7141 gaagtaacca atttctaatt cttttggctg ttacatatat tgtgtacttg tttacaataa
     7201 ggtctaaaac tgcctactaa tgaagcttta gctctcttac ccattcttta tacttattgg
     7261 aagataatag gtgctatgga aggaaaagtc agggtaagga gactgggaag aggaggccat
     7321 aattttaaat gtggtgatca ggttaggctt tattgatgtc tccacttcca ttctctgtgt
     7381 cattttgaaa atctatttgc tgttaattta atggggtttt aggaaggaac tgaaggaaat
     7441 ttatatattg agtgcagtat gtttaaatgg aagtcccaca gcacttttca gttgagttaa
     7501 caaataacga atgacaataa catgtttaca gagcatctac tatatgccaa gtattgtttt
     7561 aggaactgaa gatatggtag agaataggaa taataaaagc tggcccttgt atagtttatg
     7621 ttctagtggg agcaaataat aacagtaata gtgcaggatg tcaagtagtg gtaagtactg
     7681 tggagaataa agcaagggga ggggatgtaa ggtgatggtg aattggtact gtcccataaa
     7741 cagtggtttc tgatgtgatt acttatgatc agacacttga aagaaataag ggaatgaatc
     7801 acagggacat ctaagagaga ggagcattcc agatagaaca gcagttcgaa ggccctgagc
     7861 tcagtatgtg tttggtgtat ttaggactag gaggccagtg tggctagagc agagtggggg
     7921 aggggagggt gataggaata ggatcagatc atacatgctc tcacagactg cagcaaagac
     7981 ttggattatg agttggggag tcagttgcaa tgaactgaga tgtggctgac tgcaggagga
     8041 ataagtagta ggaagcgggt ccaggaggtt gttttagcca tgttaagttt aagatacttt
     8101 ctaaaaatcc aagtggagat gtaccagcct ggaatccagg ggcaggctgt ggctgaagat
     8161 gtaattgttg gtgccttctt aaaggttaaa cagaaattta ctagctgtgt gagaggagaa
     8221 gtgcattctg ggtaaatgga atagaataaa gaaaaaagta cgaaaaagca aacctggttc
     8281 aggaattctc cagactggtg gtgttggccc acagggtgtg tgatggagaa tgggtgaaga
     8341 tgaaactgaa aaggcaagca gggaggctat tgtgcaggac tttgtaggac atgctaagga
     8401 atctggactt tattctgcca tgaggctgct caaccatttt tatgcctcag cataactgag
     8461 ggctacaaca taacacccat cactcaacaa gcatggcagc gattttcatg ggataggaaa
     8521 tgtgtatggg agcaaaaggg acatgggtga ggggtgttga tgatgccaca tatacctgtg
     8581 tgtatgtgaa actttgaaaa atccctgaga tggctctgat atgcccccca tattccatat
     8641 gtttactccc tggggtgagg tggggcaggg agggggtacc ctctgcttag aaatcgctgc
     8701 aagcaatggc aagccattaa agaattttct ttttaaataa tcagatttgc attttagaaa
     8761 ggcaatttta gcttcagtgt agagagtgga cccaatgggg aagaggttag gagaccattt
     8821 ccatagtctg ggtagaagac aattagctcc ttgaataagt ctggagaggg aatgtttaac
     8881 tcctagccca caggcaaaat gtgtggccaa aggaatgaat attttgtgga agtattgatc
     8941 agaaagataa tgagtcaagg atccctaatg gtatatatgt ctgagtctta tttaatataa
     9001 gaagagcatg gttgcctgcc atggctctgc tgccgtcacc ctggctatcc cttaataagc
     9061 ccaggaaatt gttcaaatat ttctgccatt tgtgttttca gcttgccttg ttcagggact
     9121 tcacatagaa tggtataact ggagtacagg gtgtgtatgt agtggcgggt gatagaaaat
     9181 tagactggaa aagtagacca ggctccaggg caggagggtc tcttttcctc actccattta
     9241 atttaaaaaa gaaatagttt caattatata agcattgtga ttaatgcagg cagttggagt
     9301 actttctaaa tcagaaaagt aaaagtgctg ctccttctgc atatctctag aaatttgtta
     9361 tggggaagtc tttatcaaag aatgtcccta tgatttcagt agaatttctt aagaaaagag
     9421 cttctaaaaa cattcagtca gcccagcaca ttccaaatta aataatgaga agtgtgttta
     9481 gtatttattt aggaattctt ttctgaacaa aaaaacgttt tcaatggtct aggcacttcc
     9541 tttttcttcc aaagaaatgg taataacagg acactagaag tacctttctg tgtaaagcaa
     9601 acatcttgtc agttttcctt actttgtact tttcagtctc tgctgtttac catttttgtc
     9661 caggatcaga gacctccagt aaaataaaag gaatttctgt ttattgtctc cttgataatc
     9721 ttgatttcta aactccttta ctcctctctt gaaggtattt gttttactga caaaagaatg
     9781 gatccaggtc atttagtaga gttctgaaga gaattcttag agcactctat atattcaaac
     9841 ctccgtattt tttgatacaa aaaggactga tgaaagggag acgtgattct tttgaaagat
     9901 taattcacag aattttttat cacagttgaa atatcaattg caataacaac tgaaaactga
     9961 ttgctattac tgaacactgc ccttaggtgg ctcactctta gaagacacaa agtcactgga
    10021 ctacaatcct ttagggcagg gattgtgtct cttgctcgtt gtatatacat ggttcttaca
    10081 cagtgcctgg cattcaaaaa atgcattcag aaaaatttgg tattcaaaaa atgcttgatg
    10141 aattgactga ctgcctgaat gaataaataa attggtggat taatgactga atggagtaca
    10201 gaagactgtg gtcccagaag accttaacat tgagcttgct gcagactgaa tgtttgcctc
    10261 ctctcaaaat taatatgttg aaacctaatc cttaatgtga tagtattagg atgtggggcc
    10321 tttggaaagt gattaggtta tgaaggtgga gccctcgtga atgggagtag tatccttata
    10381 aaagataccc cagagaggtc ccttgtccct tccaacatgt gaggctacag tgaaaagatg
    10441 gccatctgta aaccaggaag tgagtcctca ccagatacca catctgttgt gctttgatct
    10501 tggatttccc tgtccccaga actgtggtaa ataaatttct gttgtttgta agcca
//
