LOCUS       NM_001322940           11177 bp    mRNA    linear   PRI 06-APR-2024
DEFINITION  Homo sapiens dermatan sulfate epimerase (DSE), transcript variant
            6, mRNA.
ACCESSION   NM_001322940
VERSION     NM_001322940.2
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 11177)
  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 11177)
  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 11177)
  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 11177)
  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 11177)
  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 11177)
  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 11177)
  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 11177)
  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 11177)
  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 11177)
  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.
            
            On Jun 2, 2019 this sequence version replaced NM_001322940.1.
            
            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 (6) contains alternate 5' exon
            structure, and it thus differs in the 5' UTR and initiates
            translation from a downstream in-frame start codon, compared to
            variant 1. The encoded isoform (c) is shorter at the N-terminus,
            compared to isoform a. Both variants 6 and 7 encode isoform c.
            
            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 :: SRR1660805.5680.1,
                                           SRR1660809.14166.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2142680, SAMEA2144120
                                           [ECO:0000348]
            ##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
            736-1200            Z84488.1           65169-65633
            1201-1454           Z84488.1           92545-92798
            1455-1694           Z84488.1           96925-97164
            1695-1902           Z84488.1           99314-99521
            1903-11177          Z84488.1           101558-110832
FEATURES             Location/Qualifiers
     source          1..11177
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q22.1"
     gene            1..11177
                     /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..1200
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            1201..1454
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     CDS             1346..3661
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /EC_number="5.1.3.19"
                     /note="isoform c is encoded by transcript variant 6; DS
                     epimerase; chondroitin-glucuronate 5-epimerase; squamous
                     cell carcinoma antigen recognized by T-cells 2"
                     /codon_start=1
                     /product="dermatan-sulfate epimerase isoform c"
                     /protein_id="NP_001309869.1"
                     /db_xref="GeneID:29940"
                     /db_xref="HGNC:HGNC:21144"
                     /db_xref="MIM:605942"
                     /translation="MYETSYRRGWGFQYLHNHQPTNCMALLTGSLVLMNQGYLQEAYL
                     WTKQVLTIMEKSLVLLREVTDGSLYEGVAYGSYTTRSLFQYMFLVQRHFNINHFGHPW
                     LKQHFAFMYRTILPGFQRTVAIADSNYNWFYGPESQLVFLDKFVMRNGSGNWLADQIR
                     RNRVVEGPGTPSKGQRWCTLHTEFLWYDGSLKSVPPPDFGTPTLHYFEDWGVVTYGSA
                     LPAEINRSFLSFKSGKLGGRAIYDIVHRNKYKDWIKGWRNFNAGHEHPDQNSFTFAPN
                     GVPFITEALYGPKYTFFNNVLMFSPAVSKSCFSPWVGQVTEDCSSKWSKYKHDLAASC
                     QGRVVAAEEKNGVVFIRGEGVGAYNPQLNLKNVQRNLILLHPQLLLLVDQIHLGEESP
                     LETAASFFHNVDVPFEETVVDGVHGAFIRQRDGLYKMYWMDDTGYSEKATFASVTYPR
                     GYPYNGTNYVNVTMHLRSPITRAAYLFIGPSIDVQSFTVHGDSQQLDVFIATSKHAYA
                     TYLWTGEATGQSAFAQVIADRHKILFDRNSAIKSSIVPEVKDYAAIVEQNLQHFKPVF
                     QLLEKQILSRVRNTASFRKTAERLLRFSDKRQTEEAIDRIFAISQQQQQQSKSKKNRR
                     AGKRYKFVDAVPDIFAQIEVNEKKIRQKAQILAQKELPIDEDEEMKDLLDFADVTYEK
                     HKNGGLIKGRFGQARMVTTTHSRAPSLSASYTRLFLILNIAIFFVMLAMQLTYFQRAQ
                     SLHGQRCLYAVLLIDSCILLWLYSSCSQSQC"
     exon            1455..1694
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            1695..1902
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     exon            1903..11177
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4575..4580
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      4595
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="major polyA site"
     regulatory      4701..4706
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: TATAAA"
     polyA_site      4724
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
     regulatory      7556..7561
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      7577
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
     regulatory      11152..11157
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DSE"
                     /gene_synonym="DS-epi1; DSEP; DSEPI; EDSMC2; SART-2;
                     SART2"
                     /note="hexamer: AATAAA"
     polyA_site      11177
                     /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 gttggtgaaa gatgctcctt gggatgaggt cccgcttgct cactccctgg ttggttttgc
     1261 cactgcttat gacttcttgt acaactacct gagcaagaca caacaggaga agtttcttga
     1321 agtgattgcc aatgcctcag ggtatatgta tgaaacttca tacaggagag gatggggatt
     1381 tcaatacctg cacaatcatc agcccaccaa ctgtatggct ttgctcacgg gaagcctagt
     1441 cctgatgaat caaggatatc ttcaagaagc ctacttatgg accaaacaag ttctgaccat
     1501 catggagaaa tctctggtct tgctcaggga ggtgacggat ggctccctct atgaaggagt
     1561 tgcgtatggc agctacacca ctagatcact cttccaatac atgtttctcg tccagaggca
     1621 cttcaacatc aaccactttg gccatccgtg gcttaaacaa cactttgcat ttatgtatag
     1681 aaccatcctg ccagggtttc aaaggactgt ggctattgcg gactcaaatt acaactggtt
     1741 ttatggtcca gaaagccaat tagtgttcct tgataaattt gtcatgcgta atggcagtgg
     1801 taactggcta gctgaccaaa tcagaaggaa ccgtgtggtg gaaggtccag gaacaccatc
     1861 caaagggcag cgctggtgca ctctgcacac agaatttctc tggtatgatg gcagcttgaa
     1921 atcggttcct cctccagact ttggcacccc tacactgcat tattttgaag actggggtgt
     1981 cgtgacttat ggaagtgcac tacctgcaga aatcaataga tctttccttt ccttcaagtc
     2041 tggaaaactg gggggacgtg caatatatga cattgtccac agaaacaaat acaaagattg
     2101 gatcaaagga tggagaaatt ttaatgcagg gcatgaacat cctgatcaaa actcatttac
     2161 ttttgctccc aatggtgtgc ctttcattac tgaggctctg tacgggccaa agtacacctt
     2221 cttcaacaat gttttgatgt tttccccagc tgtgtcaaag agctgctttt ctccctgggt
     2281 gggtcaggtc acagaagact gctcatcaaa atggtctaaa tacaagcatg acctggcagc
     2341 tagttgtcag gggagggtgg ttgcagcaga ggagaaaaat ggggtggttt tcatccgagg
     2401 agaaggtgtg ggagcttata acccccagct caacctgaag aatgttcaga ggaatctcat
     2461 cctcctacat ccacagctgc ttctccttgt agaccaaata cacctgggag aggagagtcc
     2521 cttggagaca gcagcgagct tcttccataa tgtggatgtt ccttttgagg agactgtggt
     2581 agatggtgtc catggggctt tcatcaggca gagagatggt ctctataaaa tgtactggat
     2641 ggacgatact ggctacagcg agaaagcaac ctttgcctca gtgacatatc ctcggggcta
     2701 tccctacaat gggacaaact atgtgaatgt caccatgcac ctccgaagtc ccatcaccag
     2761 ggcagcttac ctcttcatag ggccatctat agatgttcag agcttcactg tccacggaga
     2821 ctctcagcaa ctggatgtgt tcatagccac cagcaaacat gcctacgcca catacctgtg
     2881 gacaggtgag gccacaggac agtctgcctt tgcacaggtc attgctgatc gtcacaaaat
     2941 tctgtttgac cggaattcag ccatcaagag cagcattgtc cctgaggtga aggactatgc
     3001 tgctattgtg gaacagaact tgcagcattt taaaccagtg tttcagctgc tggagaagca
     3061 gatactgtcc cgagtccgga acacagctag ctttaggaag actgctgaac gcctgctgag
     3121 attttcagat aagagacaga ctgaggaggc cattgacagg atttttgcca tatcacagca
     3181 acagcagcag caaagcaagt caaagaaaaa ccgaagggca ggcaaacgct ataaatttgt
     3241 ggatgctgtc cctgatattt ttgcacagat tgaagtcaat gagaaaaaga ttagacagaa
     3301 agctcagatt ttggcacaga aagaactacc catagatgaa gatgaagaaa tgaaagacct
     3361 tttagatttt gcagatgtaa catacgagaa acataaaaat gggggcttga ttaaaggccg
     3421 gtttggacag gcacggatgg tgacaactac acacagcagg gccccatcac tgtctgcttc
     3481 ctataccagg ttgttcctga ttctgaacat tgctattttc tttgtcatgt tggcaatgca
     3541 actgacttat ttccagaggg cccagagcct acatggccaa agatgtcttt atgcagttct
     3601 tctcatagat agctgtattt tattatggtt gtactcttct tgttcccaat cacagtgtta
     3661 gcactgaagc tataaattac ctggtcattt tgtgatcaca agagtctatg caaaaaaaaa
     3721 aatttcttta ccccagatta tcagattttt ttccctcaga ttcattttaa caaattaagg
     3781 gaagatattt tgacacaaga aagcaggaac gtggagaaat tggagcagga aaagaaatta
     3841 tcaaagcaat agaaatagct tggtggtcct atggtgtttt tggaagtatt tggcattgct
     3901 aattgagcag tccatatagt actactttta gaagaaacaa aaagtctatt ttttaaagta
     3961 atgttttttc ttatgagaaa aaggtttaga tagaattggg ttttattaat attaatttaa
     4021 tgctattagc aatttccata tactatattg tggaaaagac tgaagaatac aattctgaga
     4081 aatataaaaa aattttaatg gtatactcat gttgaaagat aaatgttgct aagtcctggt
     4141 atgatggtgt gagcttcctt ggggaagtac ttcttgagtt atgtaactaa caggatgttt
     4201 tactacagat ctggatggct attcagataa catggcaaaa aatgatagca gaagatcatt
     4261 aaaaacttaa aatatatttt attagaaaac atttatctat gaatgaatat ttccttgatg
     4321 ctggtctctg cacacatatg cttggttact tgcatgcatt cattggttgt tcaataagtg
     4381 agatgattac agataatact gtattttcct tatatggaaa accgttatag acccaataac
     4441 aactaaacct ttcaaaagaa aatattttct attatgaatg ttgattttca taccaaagaa
     4501 gatggagagt ctaaaatttg gatatgattc ttatgttttt ttaatagaaa accttcttca
     4561 agtttatttt cctaaataaa catcataatt gtgaattttc tctagtattc ttcttctttg
     4621 ttccattata ttcaaaatgc attaacattt tccaaaattt ttgaagagag atctttattt
     4681 ggacgtgtat tcattaaata tataaagtag tgtttgaatc aaaagaagta ttttctctgc
     4741 ttattaacct taattgttgt ttaagcatat tttaaatatt taaaacaata gccaattctg
     4801 atatttaagt agcacccaac ttttaaaagc ataaaatttt caatcaactc ctcagaaggt
     4861 aacagcagca tagaatacta gaaaaataat ccatagtttc tacttgagca taagaaaatg
     4921 atatacttaa aaggaactta ataaattatc atacattcag catatttgag tcatatattt
     4981 ctcctttgaa acaaaatatg ttcagctcaa attttacagt aaggacacac tcactgattt
     5041 ataggtgtaa agtaacaaca gtaacctttc ctcttacttg ctcttttagt tcacagcaat
     5101 accagtatgt aaccaaaaga caagctagag aaacttttaa gtacctttct gcagttctaa
     5161 tttgaacctt cttgcataaa gaaaacacaa gtttgacttt taactgtgct tcacttatta
     5221 tgcttggaat ctagaaaacg acttctgagg aagtaatttt tttcccctct catggaaagt
     5281 ctctagggag gatgtcatta cacactgttt aaaagaataa tgttttcaaa agaataatgc
     5341 ttccgtttgt cctgcatgga tgctcttact aggatttaaa cttgctttat gtgacagatt
     5401 ctccatttac ttaacctcac tcaacattcc tctcttttac tctttctcac tcaaaaggat
     5461 gaactgtctg aaatgatcaa aaggaaattt tgaaagaaaa aaaaaaggaa aattattctt
     5521 tgaggttacc aagcaaacct gatctcagat ccaaactgag acatactttc taacagagat
     5581 gaaaagtgca agtgagtgcc aaactcgctt ttcttttgtt ttcattaggt taaggcttga
     5641 caatacgtta gtcgccacag catgatccag tgtaacatat tagttcattt taaagtagtc
     5701 tttttaaaat acgcatcttt aaaacaaaat gaattaaaat tatgtgtttt ttttttttct
     5761 tctaatgaac ctggtattta tttccttaaa aagaaacttc ctcaggcagt gacttaagtg
     5821 gttaagtgaa aaaaaaaaat gctgaaacaa atcacccctc ttcataatga aacatgtttt
     5881 ttttaatcag ggatagtgca tatttgagta aaactaggga actttttgta acttgaaaac
     5941 aaagcaatgt taaatctccc ttgaaactga gtaatcagtt atggaatctg tttcaatgct
     6001 gctcactatg acaggaatgt ttcaagttca tttgataata tgtgagctgt tgttcagggg
     6061 attggcagga ctcttggtcc tagccttaaa gaaaatttga gaatcactag catacagagc
     6121 ttgtcagtgc agtaaaagtg gtatattcct gggaagctga ggtgggagta ttgcctgagc
     6181 ttaggagttc tgtgctgcag tgagctatga ctgtgccact gcactccagc cttggagaca
     6241 gagtgagacc gtgtttctct cttttttttt tttttaagta tattcccttg tttataactg
     6301 attagcttat ttcagttgat ggtagatgag acctatggtg gtggatgaga cccagaattt
     6361 tcagagagaa cattcttttg acaacattgt tttaatcgtc aaagtcaggt ggaagaccgt
     6421 gttctggaac tattttaatt gttaaaatgt atcacctaag ataatgaatt cttccacaaa
     6481 tattttagtc atagttttta agtaccacgt attctaaggt tatcagaaaa tatgtcttaa
     6541 cagaatgttt tgcatactga ataatttgtt tttgaaaagg aaaatttaca tttgacttac
     6601 tcagttttta aaaaattatt tttatttcta gagacacggt cctttctgca tcacccaggc
     6661 tgaagtgtag tggcgtgatc gtagctcact gcagccgcaa acttcccatc ttaagcgatt
     6721 cttctgcctc agccttccaa agtactggga ttagaggcat aggtcatcat gcccggccaa
     6781 gttaaaaaaa tttttgatag ttcacaaacc actcacaaaa gaatctgaaa tttctccaag
     6841 tgttaagaga aagcaagcta tgaaatgcta tatttgtagg cttaaaagta aattagtgtg
     6901 ttttcttaaa aatctaaacc aagattaaaa tgaatatagt cataggtatg aggggcatgt
     6961 aatttatctt ccgactggag atacctttga gagttaaagg aggagcaatt aattgttatt
     7021 ccaggacaac agatataaat cgagattata ctaggtgaac tgggacatat ggtcatcttt
     7081 gtcatagctt aattcaggaa aaaaggagtt agggaagtct gaaggtctaa ctcaaagttt
     7141 gatgcttttt aagcaagttt agggaacttg agatgacctg attgagaccc ctaaatctac
     7201 agatgaggaa agcaagcctc aagcaagggg ggcctgatcc tttccctgtt cgctgtgtat
     7261 tccctgtctg tggcaaagcc cattgccttg attctcttct ctttactttc atgttgagaa
     7321 gtagtttctt tctgcagttt atttaattta ctggcaaaat gacgtatttt tttttcagca
     7381 atgtttcagc tagatatttg ctttatgcat gtaatgtcaa tgaagtactc ataagttttc
     7441 aagaaatgac tgatataaat catgtgttcc actacatagt ctaaatattt agtatttggt
     7501 catctatttt aatatgttca aattctgtta aacaagacat agtcactatg tgaagaataa
     7561 aaatagacaa agttgcatta tgacttttct tcttgcatat acagtttccc tcttggtttt
     7621 gggatttttt taattgaagt tttatttggc ataaattatg aacatacatg attgaaaaag
     7681 tatagtacta gaagccttat ttaaaaaaca aaacaataaa ttatctgtcc cttcccctct
     7741 cattcttagt ttgtacttcc cagaagtaac caatttctaa ttcttttggc tgttacatat
     7801 attgtgtact tgtttacaat aaggtctaaa actgcctact aatgaagctt tagctctctt
     7861 acccattctt tatacttatt ggaagataat aggtgctatg gaaggaaaag tcagggtaag
     7921 gagactggga agaggaggcc ataattttaa atgtggtgat caggttaggc tttattgatg
     7981 tctccacttc cattctctgt gtcattttga aaatctattt gctgttaatt taatggggtt
     8041 ttaggaagga actgaaggaa atttatatat tgagtgcagt atgtttaaat ggaagtccca
     8101 cagcactttt cagttgagtt aacaaataac gaatgacaat aacatgttta cagagcatct
     8161 actatatgcc aagtattgtt ttaggaactg aagatatggt agagaatagg aataataaaa
     8221 gctggccctt gtatagttta tgttctagtg ggagcaaata ataacagtaa tagtgcagga
     8281 tgtcaagtag tggtaagtac tgtggagaat aaagcaaggg gaggggatgt aaggtgatgg
     8341 tgaattggta ctgtcccata aacagtggtt tctgatgtga ttacttatga tcagacactt
     8401 gaaagaaata agggaatgaa tcacagggac atctaagaga gaggagcatt ccagatagaa
     8461 cagcagttcg aaggccctga gctcagtatg tgtttggtgt atttaggact aggaggccag
     8521 tgtggctaga gcagagtggg ggaggggagg gtgataggaa taggatcaga tcatacatgc
     8581 tctcacagac tgcagcaaag acttggatta tgagttgggg agtcagttgc aatgaactga
     8641 gatgtggctg actgcaggag gaataagtag taggaagcgg gtccaggagg ttgttttagc
     8701 catgttaagt ttaagatact ttctaaaaat ccaagtggag atgtaccagc ctggaatcca
     8761 ggggcaggct gtggctgaag atgtaattgt tggtgccttc ttaaaggtta aacagaaatt
     8821 tactagctgt gtgagaggag aagtgcattc tgggtaaatg gaatagaata aagaaaaaag
     8881 tacgaaaaag caaacctggt tcaggaattc tccagactgg tggtgttggc ccacagggtg
     8941 tgtgatggag aatgggtgaa gatgaaactg aaaaggcaag cagggaggct attgtgcagg
     9001 actttgtagg acatgctaag gaatctggac tttattctgc catgaggctg ctcaaccatt
     9061 tttatgcctc agcataactg agggctacaa cataacaccc atcactcaac aagcatggca
     9121 gcgattttca tgggatagga aatgtgtatg ggagcaaaag ggacatgggt gaggggtgtt
     9181 gatgatgcca catatacctg tgtgtatgtg aaactttgaa aaatccctga gatggctctg
     9241 atatgccccc catattccat atgtttactc cctggggtga ggtggggcag ggagggggta
     9301 ccctctgctt agaaatcgct gcaagcaatg gcaagccatt aaagaatttt ctttttaaat
     9361 aatcagattt gcattttaga aaggcaattt tagcttcagt gtagagagtg gacccaatgg
     9421 ggaagaggtt aggagaccat ttccatagtc tgggtagaag acaattagct ccttgaataa
     9481 gtctggagag ggaatgttta actcctagcc cacaggcaaa atgtgtggcc aaaggaatga
     9541 atattttgtg gaagtattga tcagaaagat aatgagtcaa ggatccctaa tggtatatat
     9601 gtctgagtct tatttaatat aagaagagca tggttgcctg ccatggctct gctgccgtca
     9661 ccctggctat cccttaataa gcccaggaaa ttgttcaaat atttctgcca tttgtgtttt
     9721 cagcttgcct tgttcaggga cttcacatag aatggtataa ctggagtaca gggtgtgtat
     9781 gtagtggcgg gtgatagaaa attagactgg aaaagtagac caggctccag ggcaggaggg
     9841 tctcttttcc tcactccatt taatttaaaa aagaaatagt ttcaattata taagcattgt
     9901 gattaatgca ggcagttgga gtactttcta aatcagaaaa gtaaaagtgc tgctccttct
     9961 gcatatctct agaaatttgt tatggggaag tctttatcaa agaatgtccc tatgatttca
    10021 gtagaatttc ttaagaaaag agcttctaaa aacattcagt cagcccagca cattccaaat
    10081 taaataatga gaagtgtgtt tagtatttat ttaggaattc ttttctgaac aaaaaaacgt
    10141 tttcaatggt ctaggcactt cctttttctt ccaaagaaat ggtaataaca ggacactaga
    10201 agtacctttc tgtgtaaagc aaacatcttg tcagttttcc ttactttgta cttttcagtc
    10261 tctgctgttt accatttttg tccaggatca gagacctcca gtaaaataaa aggaatttct
    10321 gtttattgtc tccttgataa tcttgatttc taaactcctt tactcctctc ttgaaggtat
    10381 ttgttttact gacaaaagaa tggatccagg tcatttagta gagttctgaa gagaattctt
    10441 agagcactct atatattcaa acctccgtat tttttgatac aaaaaggact gatgaaaggg
    10501 agacgtgatt cttttgaaag attaattcac agaatttttt atcacagttg aaatatcaat
    10561 tgcaataaca actgaaaact gattgctatt actgaacact gcccttaggt ggctcactct
    10621 tagaagacac aaagtcactg gactacaatc ctttagggca gggattgtgt ctcttgctcg
    10681 ttgtatatac atggttctta cacagtgcct ggcattcaaa aaatgcattc agaaaaattt
    10741 ggtattcaaa aaatgcttga tgaattgact gactgcctga atgaataaat aaattggtgg
    10801 attaatgact gaatggagta cagaagactg tggtcccaga agaccttaac attgagcttg
    10861 ctgcagactg aatgtttgcc tcctctcaaa attaatatgt tgaaacctaa tccttaatgt
    10921 gatagtatta ggatgtgggg cctttggaaa gtgattaggt tatgaaggtg gagccctcgt
    10981 gaatgggagt agtatcctta taaaagatac cccagagagg tcccttgtcc cttccaacat
    11041 gtgaggctac agtgaaaaga tggccatctg taaaccagga agtgagtcct caccagatac
    11101 cacatctgtt gtgctttgat cttggatttc cctgtcccca gaactgtggt aaataaattt
    11161 ctgttgtttg taagcca
//
