LOCUS       NM_014243               6244 bp    mRNA    linear   PRI 06-JUN-2024
DEFINITION  Homo sapiens ADAM metallopeptidase with thrombospondin type 1 motif
            3 (ADAMTS3), mRNA.
ACCESSION   NM_014243
VERSION     NM_014243.3
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 6244)
  AUTHORS   Gibson,S.V., Madzharova,E., Tan,A.C., Allen,M.D., Keller,U.A.D.,
            Louise Jones,J., Carter,E.P. and Grose,R.P.
  TITLE     ADAMTS3 restricts cancer invasion in models of early breast cancer
            progression through enhanced fibronectin degradation
  JOURNAL   Matrix Biol 121, 74-89 (2023)
   PUBMED   37336268
  REMARK    GeneRIF: ADAMTS3 restricts cancer invasion in models of early
            breast cancer progression through enhanced fibronectin degradation.
REFERENCE   2  (bases 1 to 6244)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   3  (bases 1 to 6244)
  AUTHORS   Scheuerle,A.E., Sweed,N.T., Timmons,C.F., Smith,E.D., Alcaraz,W.A.
            and Shinde,D.N.
  TITLE     An additional case of Hennekam lymphangiectasia-lymphedema syndrome
            caused by loss-of-function mutation in ADAMTS3
  JOURNAL   Am J Med Genet A 176 (12), 2858-2861 (2018)
   PUBMED   30450763
  REMARK    GeneRIF: There is report of one family supporting mutations in
            ADAMTS3 as causative for the phenotype labeled as HKLLS3. Here, we
            report an additional case of HKLLS that appears to be associated
            with homozygous nonsense mutation of ADAMTS3.
REFERENCE   4  (bases 1 to 6244)
  AUTHORS   Aydemir,A.T., Alper,M. and Kockar,F.
  TITLE     SP1-mediated downregulation of ADAMTS3 gene expression in
            osteosarcoma models
  JOURNAL   Gene 659, 1-10 (2018)
   PUBMED   29518549
  REMARK    GeneRIF: Molecular cloning and in silico analysis identify
            potential transcription factor binding sites in the ADAMTS3
            promoter region and show that SP1 downregulated ADAMTS3
            transcriptional activity in osteosarcoma cell lines. As consistent
            with the transcriptional activity, mRNA, and protein expression
            levels were also decreased by SP1.
REFERENCE   5  (bases 1 to 6244)
  AUTHORS   Brouillard,P., Dupont,L., Helaers,R., Coulie,R., Tiller,G.E.,
            Peeden,J., Colige,A. and Vikkula,M.
  TITLE     Loss of ADAMTS3 activity causes Hennekam
            lymphangiectasia-lymphedema syndrome 3
  JOURNAL   Hum Mol Genet 26 (21), 4095-4104 (2017)
   PUBMED   28985353
  REMARK    GeneRIF: Results corroborate the recent in vitro and murine data
            that suggest a close functional interaction between ADAMTS3 and
            CCBE1 in triggering VEGFR3 signaling, a cornerstone for the
            differentiation and function of lymphatic endothelial cells.
REFERENCE   6  (bases 1 to 6244)
  AUTHORS   Colige,A., Vandenberghe,I., Thiry,M., Lambert,C.A., Van Beeumen,J.,
            Li,S.W., Prockop,D.J., Lapiere,C.M. and Nusgens,B.V.
  TITLE     Cloning and characterization of ADAMTS-14, a novel ADAMTS
            displaying high homology with ADAMTS-2 and ADAMTS-3
  JOURNAL   J Biol Chem 277 (8), 5756-5766 (2002)
   PUBMED   11741898
REFERENCE   7  (bases 1 to 6244)
  AUTHORS   Fernandes,R.J., Hirohata,S., Engle,J.M., Colige,A., Cohn,D.H.,
            Eyre,D.R. and Apte,S.S.
  TITLE     Procollagen II amino propeptide processing by ADAMTS-3. Insights on
            dermatosparaxis
  JOURNAL   J Biol Chem 276 (34), 31502-31509 (2001)
   PUBMED   11408482
REFERENCE   8  (bases 1 to 6244)
  AUTHORS   Tang,B.L.
  TITLE     ADAMTS: a novel family of extracellular matrix proteases
  JOURNAL   Int J Biochem Cell Biol 33 (1), 33-44 (2001)
   PUBMED   11167130
  REMARK    Review article
REFERENCE   9  (bases 1 to 6244)
  AUTHORS   Hurskainen,T.L., Hirohata,S., Seldin,M.F. and Apte,S.S.
  TITLE     ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of
            zinc metalloproteases. General features and genomic distribution of
            the ADAM-TS family
  JOURNAL   J Biol Chem 274 (36), 25555-25563 (1999)
   PUBMED   10464288
REFERENCE   10 (bases 1 to 6244)
  AUTHORS   Tang,B.L. and Hong,W.
  TITLE     ADAMTS: a novel family of proteases with an ADAM protease domain
            and thrombospondin 1 repeats
  JOURNAL   FEBS Lett 445 (2-3), 223-225 (1999)
   PUBMED   10094461
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC104814.5, AF247668.1,
            AK295131.1, BC130287.1, AB002364.1 and BC016451.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_014243.2.
            
            Summary: This gene encodes a member of the ADAMTS (a disintegrin
            and metalloproteinase with thrombospondin motifs) protein family.
            Members of the family share several distinct protein modules,
            including a propeptide region, a metalloproteinase domain, a
            disintegrin-like domain, and a thrombospondin type 1 (TS) motif.
            Individual members of this family differ in the number of
            C-terminal TS motifs, and some have unique C-terminal domains. The
            encoded preproprotein is proteolytically processed to generate the
            mature protease. This protease, a member of the procollagen
            aminopropeptidase subfamily of proteins, may play a role in the
            processing of type II fibrillar collagen in articular cartilage.
            [provided by RefSeq, Feb 2016].
            
            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 :: AB002364.1, BC130287.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000286657.10/ ENSP00000286657.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-422               AC104814.5         80927-81348         c
            423-871             AF247668.1         1-449
            872-963             AK295131.1         370-461
            964-5172            BC130287.1         539-4747
            5173-5397           AB002364.1         4703-4927
            5398-6243           AB002364.1         4929-5774
            6244-6244           BC016451.1         3264-3264
FEATURES             Location/Qualifiers
     source          1..6244
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q13.3"
     gene            1..6244
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /note="ADAM metallopeptidase with thrombospondin type 1
                     motif 3"
                     /db_xref="GeneID:9508"
                     /db_xref="HGNC:HGNC:219"
                     /db_xref="MIM:605011"
     exon            1..528
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     CDS             460..4077
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /EC_number="3.4.24.-"
                     /note="zinc metalloendopeptidase; a disintegrin-like and
                     metalloprotease (reprolysin type) with thrombospondin type
                     1 motif, 3; a disintegrin and metalloproteinase with
                     thrombospondin motifs 3; ADAM-TS3; ADAMTS-3; PC II-NP;
                     ADAM-TS 3; procollagen II N-proteinase; procollagen II
                     amino propeptide-processing enzyme"
                     /codon_start=1
                     /product="A disintegrin and metalloproteinase with
                     thrombospondin motifs 3 preproprotein"
                     /protein_id="NP_055058.2"
                     /db_xref="CCDS:CCDS3553.1"
                     /db_xref="GeneID:9508"
                     /db_xref="HGNC:HGNC:219"
                     /db_xref="MIM:605011"
                     /translation="MVLLSLWLIAAALVEVRTSADGQAGNEEMVQIDLPIKRYREYEL
                     VTPVSTNLEGRYLSHTLSASHKKRSARDVSSNPEQLFFNITAFGKDFHLRLKPNTQLV
                     APGAVVEWHETSLVPGNITDPINNHQPGSATYRIRRTEPLQTNCAYVGDIVDIPGTSV
                     AISNCDGLAGMIKSDNEEYFIEPLERGKQMEEEKGRIHVVYKRSAVEQAPIDMSKDFH
                     YRESDLEGLDDLGTVYGNIHQQLNETMRRRRHAGENDYNIEVLLGVDDSVVRFHGKEH
                     VQNYLLTLMNIVNEIYHDESLGVHINVVLVRMIMLGYAKSISLIERGNPSRSLENVCR
                     WASQQQRSDLNHSEHHDHAIFLTRQDFGPAGMQGYAPVTGMCHPVRSCTLNHEDGFSS
                     AFVVAHETGHVLGMEHDGQGNRCGDETAMGSVMAPLVQAAFHRYHWSRCSGQELKRYI
                     HSYDCLLDDPFDHDWPKLPELPGINYSMDEQCRFDFGVGYKMCTAFRTFDPCKQLWCS
                     HPDNPYFCKTKKGPPLDGTECAAGKWCYKGHCMWKNANQQKQDGNWGSWTKFGSCSRT
                     CGTGVRFRTRQCNNPMPINGGQDCPGVNFEYQLCNTEECQKHFEDFRAQQCQQRNSHF
                     EYQNTKHHWLPYEHPDPKKRCHLYCQSKETGDVAYMKQLVHDGTHCSYKDPYSICVRG
                     ECVKVGCDKEIGSNKVEDKCGVCGGDNSHCRTVKGTFTRTPRKLGYLKMFDIPPGARH
                     VLIQEDEASPHILAIKNQATGHYILNGKGEEAKSRTFIDLGVEWDYNIEDDIESLHTD
                     GPLHDPVIVLIIPQENDTRSSLTYKYIIHEDSVPTINSNNVIQEELDTFEWALKSWSQ
                     CSKPCGGGFQYTKYGCRRKSDNKMVHRSFCEANKKPKPIRRMCNIQECTHPLWVAEEW
                     EHCTKTCGSSGYQLRTVRCLQPLLDGTNRSVHSKYCMGDRPESRRPCNRVPCPAQWKT
                     GPWSECSVTCGEGTEVRQVLCRAGDHCDGEKPESVRACQLPPCNDEPCLGDKSIFCQM
                     EVLARYCSIPGYNKLCCESCSKRSSTLPPPYLLEAAETHDDVISNPSDLPRSLVMPTS
                     LVPYHSETPAKKMSLSSISSVGGPNAYAAFRPNSKPDGANLRQRSAQQAGSKTVRLVT
                     VPSSPPTKRVHLSSASQMAAASFFAASDSIGASSQARTSKKDGKIIDNRRPTRSSTLE
                     R"
     exon            529..556
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            557..963
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            964..1120
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            1121..1320
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            1321..1404
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            1405..1561
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            1562..1667
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            1668..1811
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            1812..1944
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            1945..2058
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            2059..2204
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            2205..2380
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            2381..2514
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            2515..2638
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            2639..2719
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            2720..2883
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            2884..3049
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            3050..3182
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            3183..3390
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            3391..3508
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     exon            3509..6244
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /inference="alignment:Splign:2.1.0"
     regulatory      6222..6227
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /note="hexamer: AATAAA"
     polyA_site      6244
                     /gene="ADAMTS3"
                     /gene_synonym="ADAMTS-4; HKLLS3"
                     /note="major polyA site"
ORIGIN      
        1 ctctttctcc cgctcccgct cgctcgtctc tctcgctaat acttccccct gctgtgctcc
       61 ggggaaccca agcattctcc gcgctaacct tagggaccaa tggtgctcga aaagcctcga
      121 aaaagctgct ttgggcagag atagttggaa agcccctcgt cccttccccc tctcccaggc
      181 ttagcctgtg cccgcttaca gcaccttctc gctcctgcac actctgtgtt gggaggacgg
      241 ggtgagaagg tgaagtggaa aaaactgcag agcagagggg gccagtctca gagctcaaat
      301 ttcattttca ttgaagcaaa gcacagaaga tcattttttt ctatttcgca ttttttccct
      361 tttccttttt ttcttaaaga aacttatttt gggcgggggg ggtgggtttg ctctgggcat
      421 ttgctttgcc cagtagttgg aaagtgaact cgactcgtga tggttctcct gtcactttgg
      481 ttgatagcag ccgctctggt agaggttagg acttcagctg atggacaagc tggtaatgaa
      541 gaaatggtgc aaatagattt accaataaag agatatagag agtatgagct ggtgactcca
      601 gtcagcacaa atctagaagg acgctatctc tcccatactc tttctgcgag tcacaaaaag
      661 aggtcagcga gggacgtgtc ttccaaccct gagcagttgt tctttaacat cacggcattt
      721 ggaaaagatt ttcatctgcg actaaagccc aacactcaac tagtagctcc tggggctgtt
      781 gtggagtggc atgagacatc tctggtgcct gggaatataa ccgatcccat taacaaccat
      841 caaccaggaa gtgctacgta tagaatccgg agaacagagc ctttgcagac taactgtgct
      901 tatgttggtg acatcgtgga cattccagga acctctgttg ccatcagcaa ctgtgatggt
      961 ctggctggaa tgataaaaag tgataatgaa gagtatttca ttgaaccctt ggaaagaggt
     1021 aaacagatgg aggaagaaaa aggaaggatt catgttgtct acaagagatc agctgtagaa
     1081 caggctccca tagacatgtc caaagacttc cactacagag agtcggacct ggaaggcctt
     1141 gatgatctag gtactgttta tggcaacatc caccagcagc tgaatgaaac aatgagacgc
     1201 cgcagacacg cgggagaaaa cgattacaat atcgaggtac tgctgggagt ggatgactct
     1261 gtggtccgtt tccatggcaa agagcacgtc caaaactacc tcctgaccct aatgaacatt
     1321 gtgaatgaaa tttaccatga tgagtccctc ggagtgcata taaatgtggt cctggtgcgc
     1381 atgataatgc tgggatatgc aaagtccatc agcctcatag aaaggggaaa cccatccaga
     1441 agcttggaga atgtgtgtcg ctgggcgtcc caacagcaaa gatctgatct caaccactct
     1501 gaacaccatg accatgcaat ttttttaacc aggcaagact ttggacctgc tggaatgcaa
     1561 ggatatgctc cagtcaccgg catgtgtcat ccagtgagaa gttgtaccct gaatcatgag
     1621 gatggttttt catctgcttt tgtagtagcc catgaaacgg gccatgtgtt gggaatggag
     1681 catgatggac aaggcaacag gtgtggtgat gagactgcta tgggaagtgt catggctccc
     1741 ttggtacaag cagcattcca tcgttaccac tggtcccgat gcagtggtca agaactgaaa
     1801 agatatatcc attcctatga ctgtctcctt gatgaccctt ttgatcatga ttggcctaaa
     1861 ctcccagaac ttcctggaat caattattct atggatgagc aatgtcgttt tgattttggt
     1921 gttggctata aaatgtgcac cgcgttccga acctttgacc catgtaaaca gctgtggtgt
     1981 agccatcctg ataatcccta cttttgtaag actaaaaagg gacctccact tgatgggact
     2041 gaatgtgctg ctggaaaatg gtgctataag ggtcattgca tgtggaagaa tgctaatcag
     2101 caaaaacaag atggcaattg ggggtcatgg actaaatttg gctcctgttc tcggacatgt
     2161 ggaactggtg ttcgtttcag aacacgccag tgcaataatc ccatgcccat caatggtggt
     2221 caggattgtc ctggtgttaa ttttgagtac cagctttgta acacagaaga atgccaaaaa
     2281 cactttgagg acttcagagc acagcagtgt cagcagcgaa actcccactt tgaataccag
     2341 aataccaaac accactggtt gccatatgaa catcctgacc ccaagaaaag atgccacctt
     2401 tactgtcagt ccaaggagac tggagatgtt gcttacatga aacaactggt gcatgatgga
     2461 acgcactgtt cttacaaaga tccatatagc atatgtgtgc gaggagagtg tgtgaaagtg
     2521 ggctgtgata aagaaattgg ttctaataag gttgaggata agtgtggtgt ctgtggagga
     2581 gataattccc actgccgaac cgtgaagggg acatttacca gaactcccag gaagcttggg
     2641 taccttaaga tgtttgatat accccctggg gctagacatg tgttaatcca agaagacgag
     2701 gcttctcctc atattcttgc tattaagaac caggctacag gccattatat tttaaatggc
     2761 aaaggggagg aagccaagtc gcggaccttc atagatcttg gtgtggagtg ggattataac
     2821 attgaagatg acattgaaag tcttcacacc gatggacctt tacatgatcc tgttattgtt
     2881 ttgattatac ctcaagaaaa tgatacccgc tctagcctga catataagta catcatccat
     2941 gaagactctg tacctacaat caacagcaac aatgtcatcc aggaagaatt agatactttt
     3001 gagtgggctt tgaagagctg gtctcagtgt tccaaaccct gtggtggagg tttccagtac
     3061 actaaatatg gatgccgtag gaaaagtgat aataaaatgg tccatcgcag cttctgtgag
     3121 gccaacaaaa agccgaaacc tattagacga atgtgcaata ttcaagagtg tacacatcca
     3181 ctctgggtag cagaagaatg ggaacactgc accaaaacct gtggaagttc tggctatcag
     3241 cttcgcactg tacgctgcct tcagccactc cttgatggca ccaaccgctc tgtgcacagc
     3301 aaatactgca tgggtgaccg tcccgagagc cgccggccct gtaacagagt gccctgccct
     3361 gcacagtgga aaacaggacc ctggagtgag tgttcagtga cctgcggtga aggaacggag
     3421 gtgaggcagg tcctctgcag ggctggggac cactgtgatg gtgaaaagcc tgagtcggtc
     3481 agagcctgtc aactgcctcc ttgtaatgat gaaccatgtt tgggagacaa gtccatattc
     3541 tgtcaaatgg aagtgttggc acgatactgc tccataccag gttataacaa gttatgttgt
     3601 gagtcctgca gcaagcgcag tagcaccctg ccaccaccat accttctaga agctgctgaa
     3661 actcatgatg atgtcatctc taaccctagt gacctcccta gatctctagt gatgcctaca
     3721 tctttggttc cttatcattc agagacccct gcaaagaaga tgtctttgag tagcatctct
     3781 tcagtgggag gtccaaatgc atatgctgct ttcaggccaa acagtaaacc tgatggtgct
     3841 aatttacgcc agaggagtgc tcagcaagca ggaagtaaga ctgtgagact ggtcaccgta
     3901 ccatcctccc cacccaccaa gagggtccac ctcagttcag cttcacaaat ggctgctgct
     3961 tccttctttg cagccagtga ttcaataggt gcttcttctc aggcaagaac ctcaaagaaa
     4021 gatggaaaga tcattgacaa cagacgtccg acaagatcat ccaccttaga aagatgagaa
     4081 agtgaaccaa aaaggctaga aaccagagga aaacctggac aacctctctc ttcccatggt
     4141 gcatatgctt gtttaaagtg gaaatctcta tagatcgtca gctcatttta tctgtaattg
     4201 gaagaacaga aagtgctggc tcactttcta gttgctttca tcctcctttt gttctgcatt
     4261 gactcattta ccagaattca ttggaagaaa tcaccaaaga ttattacaaa agaaaaatat
     4321 gttgctaaga ttgtgttggt cgctctctga agcagaaaag ggactggaac caattgtgca
     4381 tatcagctga ctttttgttt gttttagaaa agttacagta aaaattaaaa agagatacca
     4441 atggtttaca ctttaacaag aaattttgga tatggaacaa agaattctta gacttgtatt
     4501 cctatttatc tatattagaa atattgtatg agcaaatttg cagctgttgt gtaaatactg
     4561 tatattgcaa aaatcagtat tattttaaga gatgtgttct caaatgattg tttactatat
     4621 tacatttctg gatgttctag gtgcctgtcg ttgagtattg ccttgtttga cattctatag
     4681 gttaattttc aaagcagagt attacaaaag agaagttaga attacagcta ctgacaatat
     4741 aaagggtttt gttgaatcaa caatgtgata cgtaaattat agaaaaagaa aagaaacaca
     4801 aaagctatag atatacagat atcagcttac ctattgcctt ctatacttat aatttaaagg
     4861 attggtgtct tagtacactt gtggtcacag ggatcaacga atagtaaata atgaactcgt
     4921 gcaagacaaa actgaaaccc tctttccagg acctcagtag gcaccgttga ggtgtccttt
     4981 gtttttgtgt gtgtgtgttc ttttttaatt ttcgcattgt tgacagatac aaacagttat
     5041 actcaatgta ctgtaataat cgcaaaggaa aaagttttgg gataacttat ttgtatgttg
     5101 gtagctgaga aaaatatcat cagtctagaa ttgatatttg agtatagtag agctttgggg
     5161 ctttgaaggc aggttcaaga aagcatatgt cgatggttga gatatttatt ttccatatgg
     5221 ttcatgttca aatgttcaca accacaatgc atctgactgc aataatgtgc taataattta
     5281 tgtcagtagt caccttgctc acagcaaagc cagaaatgct ctctccaggg agtagatgta
     5341 aagtacttgt acatagaatt cagaactgaa gatatttatt aaaagttgat tttttttctt
     5401 gatagtattt ttatgtacta aatatttaca ctaatatcaa ttacatattt tggtaaacta
     5461 gagagacata attagagatg catgctttgt tctgtgcata gagaccttta agcaaactac
     5521 tacagccaac tcaaaagcta aaactgaaca aatttgatgt tatgcaaaca tcttgcattt
     5581 ttagtagttg atattaagtt gatgacttgt ttcccttcaa ggaaacatta aattgtatgg
     5641 actcagctag ctgttcaatg aaattgtgaa ttagaaacat ttttaaaagt ttttgaaaga
     5701 gataagtgca tcatgaatta catgtacatg agaggagata gtgatatcag cataatgatt
     5761 ttgaggtcag tacctgagct gtctaaaaat atattataca aactaaaatg tagatgaatt
     5821 aacctctcaa agcacagaat gtgcaagaac ttttgcattt taatcgttgt aaactaacag
     5881 cttaaactat tgactctata cctctaaaga attgctgcta ctttgtgcaa gaactttgaa
     5941 ggtcaaatta ggcaaattcc agatagtaaa acaatcccta agccttaagt cttttttttt
     6001 tcctaaaaat tcccatagaa taaaattctc tctagtttac ttgtgtgtgc atacatctca
     6061 tccacagggg aagataaaga tggtcacaca aacagtttcc ataaagatgt acatattcat
     6121 tatacttctg acctttgggc tttcttttct actaagctaa aaattccttt ttatcaaagt
     6181 gtacactact gatgctgttt gttgtactga gagcacgtac caataaaaat gttaacaaaa
     6241 tata
//
