LOCUS       NM_005359               8772 bp    mRNA    linear   PRI 12-FEB-2025
DEFINITION  Homo sapiens SMAD family member 4 (SMAD4), transcript variant 1,
            mRNA.
ACCESSION   NM_005359
VERSION     NM_005359.6
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 8772)
  AUTHORS   Mansouri,N., Mozooni,Z., Haghighi,M., Soleimani,S., Ghadyani,R.,
            Parsazad,E., Azari,S., Rezaei Tavirani,M., Kahrizi,S.,
            Rouhollahpour Ahangar,E. and Movafagh,A.
  TITLE     Clinicopathological characteristics of SMAD4 gene expressions in
            colorectal cancer patients
  JOURNAL   Cell Mol Biol (Noisy-le-grand) 70 (9), 176-180 (2024)
   PUBMED   39380261
  REMARK    GeneRIF: Clinicopathological characteristics of SMAD4 gene
            expressions in colorectal cancer patients.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 8772)
  AUTHORS   Zhou,S., Buckhaults,P., Zawel,L., Bunz,F., Riggins,G., Dai,J.L.,
            Kern,S.E., Kinzler,K.W. and Vogelstein,B.
  TITLE     Targeted deletion of Smad4 shows it is required for transforming
            growth factor beta and activin signaling in colorectal cancer cells
  JOURNAL   Proc Natl Acad Sci U S A 95 (5), 2412-2416 (1998)
   PUBMED   9482899
REFERENCE   3  (bases 1 to 8772)
  AUTHORS   Zawel,L., Dai,J.L., Buckhaults,P., Zhou,S., Kinzler,K.W.,
            Vogelstein,B. and Kern,S.E.
  TITLE     Human Smad3 and Smad4 are sequence-specific transcription
            activators
  JOURNAL   Mol Cell 1 (4), 611-617 (1998)
   PUBMED   9660945
REFERENCE   4  (bases 1 to 8772)
  AUTHORS   Derynck,R., Gelbart,W.M., Harland,R.M., Heldin,C.H., Kern,S.E.,
            Massague,J., Melton,D.A., Mlodzik,M., Padgett,R.W., Roberts,A.B.,
            Smith,J., Thomsen,G.H., Vogelstein,B. and Wang,X.F.
  TITLE     Nomenclature: vertebrate mediators of TGFbeta family signals
  JOURNAL   Cell 87 (2), 173 (1996)
   PUBMED   8861901
REFERENCE   5  (bases 1 to 8772)
  AUTHORS   Zhang,Y., Feng,X., We,R. and Derynck,R.
  TITLE     Receptor-associated Mad homologues synergize as effectors of the
            TGF-beta response
  JOURNAL   Nature 383 (6596), 168-172 (1996)
   PUBMED   8774881
REFERENCE   6  (bases 1 to 8772)
  AUTHORS   Hahn,S.A., Schutte,M., Hoque,A.T., Moskaluk,C.A., da Costa,L.T.,
            Rozenblum,E., Weinstein,C.L., Fischer,A., Yeo,C.J., Hruban,R.H. and
            Kern,S.E.
  TITLE     DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1
  JOURNAL   Science 271 (5247), 350-353 (1996)
   PUBMED   8553070
REFERENCE   7  (bases 1 to 8772)
  AUTHORS   Lin,A.E., Brunetti-Pierri,N., Lindsay,M.E., Schimmenti,L.A. and
            Starr,L.J.
  TITLE     Myhre Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   28406602
REFERENCE   8  (bases 1 to 8772)
  AUTHORS   Larsen Haidle,J., MacFarland,S.P. and Howe,J.R.
  TITLE     Juvenile Polyposis Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301642
REFERENCE   9  (bases 1 to 8772)
  AUTHORS   McDonald,J. and Stevenson,D.A.
  TITLE     Hereditary Hemorrhagic Telangiectasia
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301525
REFERENCE   10 (bases 1 to 8772)
  AUTHORS   Milewicz,D.M. and Cecchi,A.C.
  TITLE     Heritable Thoracic Aortic Disease Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301299
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AU120224.1, BC002379.2,
            AC091551.14 and BM701399.1.
            
            On Jul 29, 2019 this sequence version replaced NM_005359.5.
            
            Summary: This gene encodes a member of the Smad family of signal
            transduction proteins. Smad proteins are phosphorylated and
            activated by transmembrane serine-threonine receptor kinases in
            response to transforming growth factor (TGF)-beta signaling. The
            product of this gene forms homomeric complexes and heteromeric
            complexes with other activated Smad proteins, which then accumulate
            in the nucleus and regulate the transcription of target genes. This
            protein binds to DNA and recognizes an 8-bp palindromic sequence
            (GTCTAGAC) called the Smad-binding element (SBE). The protein acts
            as a tumor suppressor and inhibits epithelial cell proliferation.
            It may also have an inhibitory effect on tumors by reducing
            angiogenesis and increasing blood vessel hyperpermeability. The
            encoded protein is a crucial component of the bone morphogenetic
            protein signaling pathway. The Smad proteins are subject to complex
            regulation by post-translational modifications. Mutations or
            deletions in this gene have been shown to result in pancreatic
            cancer, juvenile polyposis syndrome, and hereditary hemorrhagic
            telangiectasia syndrome. [provided by RefSeq, May 2022].
            
            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 :: SRR14038192.1163847.1,
                                           SRR14372080.769196.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000342988.8/ ENSP00000341551.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-457               AU120224.1         1-457
            458-3507            BC002379.2         153-3202
            3508-8346           AC091551.14        127863-132701
            8347-8772           BM701399.1         1-426
FEATURES             Location/Qualifiers
     source          1..8772
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="18"
                     /map="18q21.2"
     gene            1..8772
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /note="SMAD family member 4"
                     /db_xref="GeneID:4089"
                     /db_xref="HGNC:HGNC:6770"
                     /db_xref="MIM:600993"
     exon            1..411
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     exon            412..787
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     CDS             539..2197
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /note="isoform a is encoded by transcript variant 1;
                     deleted in pancreatic carcinoma locus 4; mothers against
                     decapentaplegic, Drosophila, homolog of, 4; MAD homolog 4;
                     deletion target in pancreatic carcinoma 4; SMAD, mothers
                     against DPP homolog 4"
                     /codon_start=1
                     /product="mothers against decapentaplegic homolog 4
                     isoform a"
                     /protein_id="NP_005350.1"
                     /db_xref="CCDS:CCDS11950.1"
                     /db_xref="GeneID:4089"
                     /db_xref="HGNC:HGNC:6770"
                     /db_xref="MIM:600993"
                     /translation="MDNMSITNTPTSNDACLSIVHSLMCHRQGGESETFAKRAIESLV
                     KKLKEKKDELDSLITAITTNGAHPSKCVTIQRTLDGRLQVAGRKGFPHVIYARLWRWP
                     DLHKNELKHVKYCQYAFDLKCDSVCVNPYHYERVVSPGIDLSGLTLQSNAPSSMMVKD
                     EYVHDFEGQPSLSTEGHSIQTIQHPPSNRASTETYSTPALLAPSESNATSTANFPNIP
                     VASTSQPASILGGSHSEGLLQIASGPQPGQQQNGFTGQPATYHHNSTTTWTGSRTAPY
                     TPNLPHHQNGHLQHHPPMPPHPGHYWPVHNELAFQPPISNHPAPEYWCSIAYFEMDVQ
                     VGETFKVPSSCPIVTVDGYVDPSGGDRFCLGQLSNVHRTEAIERARLHIGKGVQLECK
                     GEGDVWVRCLSDHAVFVQSYYLDREAGRAPGDAVHKIYPSAYIKVFDLRQCHRQMQQQ
                     AATAQAAAAAQAAAVAGNIPGPGSVGGIAPAISLSAAAGIGVDDLRRLCILRMSFVKG
                     WGPDYPRQSIKETPCWIEIHLHRALQLLDEVLHTMPIADPQPLD"
     exon            788..962
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     exon            963..992
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     exon            993..1205
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1206..1325
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1326..1442
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1443..1493
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1494..1677
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1678..1846
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1847..1985
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1986..8772
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3486..3491
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /note="hexamer: AATAAA"
     polyA_site      3511
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /note="major polyA site"
     regulatory      8750..8755
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
                     /note="hexamer: ATTAAA"
     polyA_site      8772
                     /gene="SMAD4"
                     /gene_synonym="DPC4; JIP; MADH4; MYHRS"
ORIGIN      
        1 atgctcagtg gcttctcgac aagttggcag caacaacacg gccctggtcg tcgtcgccgc
       61 tgcggtaacg gagcggtttg ggtggcggag cctgcgttcg cgccttcccg ctctcctcgg
      121 gaggcccttc ctgctctccc ctaggctccg cggccgccca gggggtggga gcgggtgagg
      181 ggagccaggc gcccagcgag agaggccccc cgccgcaggg cggcccggga gctcgaggcg
      241 gtccggcccg cgcgggcagc ggcgcggcgc tgaggagggg cggcctggcc gggacgcctc
      301 ggggcggggg ccgaggagct ctccgggccg ccggggaaag ctacgggccc ggtgcgtccg
      361 cggaccagca gcgcgggaga gcggactccc ctcgccaccg cccgagccca ggttatcctg
      421 aatacatgtc taacaatttt ccttgcaacg ttagctgttg tttttcactg tttccaaagg
      481 atcaaaattg cttcagaaat tggagacata tttgatttaa aaggaaaaac ttgaacaaat
      541 ggacaatatg tctattacga atacaccaac aagtaatgat gcctgtctga gcattgtgca
      601 tagtttgatg tgccatagac aaggtggaga gagtgaaaca tttgcaaaaa gagcaattga
      661 aagtttggta aagaagctga aggagaaaaa agatgaattg gattctttaa taacagctat
      721 aactacaaat ggagctcatc ctagtaaatg tgttaccata cagagaacat tggatgggag
      781 gcttcaggtg gctggtcgga aaggatttcc tcatgtgatc tatgcccgtc tctggaggtg
      841 gcctgatctt cacaaaaatg aactaaaaca tgttaaatat tgtcagtatg cgtttgactt
      901 aaaatgtgat agtgtctgtg tgaatccata tcactacgaa cgagttgtat cacctggaat
      961 tgatctctca ggattaacac tgcagagtaa tgctccatca agtatgatgg tgaaggatga
     1021 atatgtgcat gactttgagg gacagccatc gttgtccact gaaggacatt caattcaaac
     1081 catccagcat ccaccaagta atcgtgcatc gacagagaca tacagcaccc cagctctgtt
     1141 agccccatct gagtctaatg ctaccagcac tgccaacttt cccaacattc ctgtggcttc
     1201 cacaagtcag cctgccagta tactgggggg cagccatagt gaaggactgt tgcagatagc
     1261 atcagggcct cagccaggac agcagcagaa tggatttact ggtcagccag ctacttacca
     1321 tcataacagc actaccacct ggactggaag taggactgca ccatacacac ctaatttgcc
     1381 tcaccaccaa aacggccatc ttcagcacca cccgcctatg ccgccccatc ccggacatta
     1441 ctggcctgtt cacaatgagc ttgcattcca gcctcccatt tccaatcatc ctgctcctga
     1501 gtattggtgt tccattgctt actttgaaat ggatgttcag gtaggagaga catttaaggt
     1561 tccttcaagc tgccctattg ttactgttga tggatacgtg gacccttctg gaggagatcg
     1621 cttttgtttg ggtcaactct ccaatgtcca caggacagaa gccattgaga gagcaaggtt
     1681 gcacataggc aaaggtgtgc agttggaatg taaaggtgaa ggtgatgttt gggtcaggtg
     1741 ccttagtgac cacgcggtct ttgtacagag ttactactta gacagagaag ctgggcgtgc
     1801 acctggagat gctgttcata agatctaccc aagtgcatat ataaaggtct ttgatttgcg
     1861 tcagtgtcat cgacagatgc agcagcaggc ggctactgca caagctgcag cagctgccca
     1921 ggcagcagcc gtggcaggaa acatccctgg cccaggatca gtaggtggaa tagctccagc
     1981 tatcagtctg tcagctgctg ctggaattgg tgttgatgac cttcgtcgct tatgcatact
     2041 caggatgagt tttgtgaaag gctggggacc ggattaccca agacagagca tcaaagaaac
     2101 accttgctgg attgaaattc acttacaccg ggccctccag ctcctagacg aagtacttca
     2161 taccatgccg attgcagacc cacaaccttt agactgaggt cttttaccgt tggggccctt
     2221 aaccttatca ggatggtgga ctacaaaata caatcctgtt tataatctga agatatattt
     2281 cacttttgtt ctgctttatc ttttcataaa gggttgaaaa tgtgtttgct gccttgctcc
     2341 tagcagacag aaactggatt aaaacaattt tttttttcct cttcagaact tgtcaggcat
     2401 ggctcagagc ttgaagatta ggagaaacac attcttatta attcttcacc tgttatgtat
     2461 gaaggaatca ttccagtgct agaaaattta gccctttaaa acgtcttaga gccttttatc
     2521 tgcagaacat cgatatgtat atcattctac agaataatcc agtattgctg attttaaagg
     2581 cagagaagtt ctcaaagtta attcacctat gttattttgt gtacaagttg ttattgttga
     2641 acatacttca aaaataatgt gccatgtggg tgagttaatt ttaccaagag taactttact
     2701 ctgtgtttaa aaagtaagtt aataatgtat tgtaatcttt catccaaaat attttttgca
     2761 agttatatta gtgaagatgg tttcaattca gattgtcttg caacttcagt tttatttttg
     2821 ccaaggcaaa aaactcttaa tctgtgtgta tattgagaat cccttaaaat taccagacaa
     2881 aaaaatttaa aattacgttt gttattccta gtggatgact gttgatgaag tatacttttc
     2941 ccctgttaaa cagtagttgt attcttctgt atttctaggc acaaggttgg ttgctaagaa
     3001 gcctataaga ggaatttctt ttccttcatt catagggaaa ggttttgtat tttttaaaac
     3061 actaaaagca gcgtcactct acctaatgtc tcactgttct gcaaaggtgg caatgcttaa
     3121 actaaataat gaataaactg aatattttgg aaactgctaa attctatgtt aaatactgtg
     3181 cagaataatg gaaacattac agttcataat aggtagtttg gatatttttg tacttgattt
     3241 gatgtgactt tttttggtat aatgtttaaa tcatgtatgt tatgatattg tttaaaattc
     3301 agtttttgta tcttggggca agactgcaaa cttttttata tcttttggtt attctaagcc
     3361 ctttgccatc aatgatcata tcaattggca gtgactttgt atagagaatt taagtagaaa
     3421 agttgcagat gtattgactg taccacagac acaatatgta tgctttttac ctagctggta
     3481 gcataaataa aactgaatct caacatacaa agttgaattc taggtttgat ttttaagatt
     3541 ttttttttct tttgcacttt tgagtccaat ctcagtgatg aggtaccttc tactaaatga
     3601 caggcaacag ccagttctat tgggcagctt tgtttttttc cctcacactc taccgggact
     3661 tccccatgga cattgtgtat catgtgtaga gttggttttt ttttttttta atttttattt
     3721 tactatagca gaaatagacc tgattatcta caagatgata aatagattgt ctacaggata
     3781 aatagtatga aataaaatca aggattatct ttcagatgtg tttacttttg cctggagaac
     3841 ttttagctat agaaacactt gtgtgatgat agtcctcctt atatcacctg gaatgaacac
     3901 agcttctact gccttgctca gaaggtcttt taaatagacc atcctagaaa ccactgagtt
     3961 tgcttatttc tgtgatttaa acatagatct tgatccaagc tacatgactt ttgtctttaa
     4021 ataacttatc taccacctca tttgtactct tgattactta caaattcttt cagtaaacac
     4081 ctaattttct tctgtaaaag tttggtgatt taagttttat tggcagtttt ataaaaagac
     4141 atcttctcta gaaattgcta actttaggtc cattttactg tgaatgagga ataggagtga
     4201 gttttagaat aacagatttt taaaaatcca gatgatttga ttaaaacctt aatcatacat
     4261 tgacataatt cattgcttct tttttttgag atatggagtc ttgctgtgtt gcccaggcag
     4321 gagtgcagtg gtatgatctc agctcactgc aacctctgcc tcccgggttc aactgattct
     4381 cctgcctcag cctccctggt agctaggatt acaggtgccc gccaccatgc ctggctaact
     4441 tttgtagttt tagtagagac ggggttttgc ctgttggcca ggctggtctt gaactcctga
     4501 cctcaagtga tccatccacc ttggcctccc aaagtgctgg gattacgggc gtgagccact
     4561 gtccctggcc tcattgttcc cttttctact ttaaggaaag ttttcatgtt taatcatctg
     4621 gggaaagtat gtgaaaaata tttgttaaga agtatctctt tggagccaag ccacctgtct
     4681 tggtttcttt ctactaagag ccataaagta tagaaatact tctagttgtt aagtgcttat
     4741 atttgtacct agatttagtc acacgctttt gagaaaacat ctagtatgtt atgatcagct
     4801 attcctgaga gcttggttgt taatctatat ttctatttct tagtggtagt catctttgat
     4861 gaataagact aaagattctc acaggtttaa aattttatgt ctactttaag ggtaaaatta
     4921 tgaggttatg gttctgggtg ggttttctct agctaattca tatctcaaag agtctcaaaa
     4981 tgttgaattt cagtgcaagc tgaatgagag atgagccatg tacacccacc gtaagacctc
     5041 attccatgtt tgtccagtgc ctttcagtgc attatcaaag ggaatccttc atggtgttgc
     5101 ctttattttc cggggagtag atcgtgggat atagtctatc tcatttttaa tagtttaccg
     5161 cccctggtat acaaagataa tgacaataaa tcactgccat ataaccttgc tttttccaga
     5221 aacatggctg ttttgtattg ctgtaaccac taaataggtt gcctatacca ttcctcctgt
     5281 gaacagtgca gatttacagg ttgcatggtc tggcttaagg agagccatac ttgagacatg
     5341 tgagtaaact gaactcatat tagctgtgct gcatttcaga cttaaaatcc atttttgtgg
     5401 ggcagggtgt ggtgtgtaaa ggggggtgtt tgtaatacaa gttgaaggca aaataaaatg
     5461 tcctgtctcc cagatgatat acatcttatt atttttaaag tttattgcta attgtaggaa
     5521 ggtgagttgc aggtatcttt gactatggtc atctggggaa ggaaaatttt acattttact
     5581 attaatgctc cttaagtgtc tatggaggtt aaagaataaa atggtaaatg tttctgtgcc
     5641 tggtttgatg gtaactggtt aatagttact caccatttta tgcagagtca cattagttca
     5701 caccctttct gagagccttt tgggagaagc agttttattc tctgagtgga acagagttct
     5761 ttttgttgat aatttctagt ttgctccctt cgttattgcc aactttactg gcattttatt
     5821 taatgatagc agattgggaa aatggcaaat ttaggttacg gaggtaaatg agtatatgaa
     5881 agcaattacc tctaaagcca gttaacaatt attttgtagg tggggtacac tcagcttaaa
     5941 gtaatgcatt tttttttccc gtaaaggcag aatccatctt gttgcagata gctatctaaa
     6001 taatctcata tcctcttttg caaagactac agagaatagg ctatgacaat cttgttcaag
     6061 cctttccatt tttttccctg ataactaagt aatttctttg aacataccaa gaagtatgta
     6121 aaaagtccat ggccttattc atccacaaag tggcatccta ggcccagcct tatccctagc
     6181 agttgtccca gtgctgctag gttgcttatc ttgtttatct ggaatcactg tggagtgaaa
     6241 ttttccacat catccagaat tgccttattt aagaagtaaa acgttttaat ttttagcctt
     6301 tttttggtgg agttatttaa tatgtatatc agaggatata ctagatggta acatttcttt
     6361 ctgtgcttgg ctatctttgt ggacttcagg ggcttctaaa acagacagga ctgtgttgcc
     6421 tttactaaat ggtctgagac agctatggtt ttgaattttt agtttttttt ttttaaccca
     6481 cttcccctcc tggtctcttc cctctctgat aattaccatt catatgtgag tgttagtgtg
     6541 cctcctttta gcattttctt cttctctttc tgattcttca tttctgactg cctaggcaag
     6601 gaaaccagat aaccaaactt actagaacgt tctttaaaac acaagtacaa actctgggac
     6661 aggacccaag acactttcct gtgaagtgct gaaaaagacc tcattgtatt ggcatttgat
     6721 atcagtttga tgtagcttag agtgcttcct gattcttgct gagtttcagg tagttgagat
     6781 agagagaagt gagtcatatt catattttcc cccttagaat aatattttga aaggtttcat
     6841 tgcttccact tgaatgctgc tcttacaaaa actggggtta caagggttac taaattagca
     6901 tcagtagcca gaggcaatac cgttgtctgg aggacaccag caaacaacac acaacaaagc
     6961 aaaacaaacc ttgggaaact aaggccattt gttttgtttt ggtgtcccct ttgaagccct
     7021 gccttctggc cttactcctg tacagatatt tttgacctat aggtgccttt atgagaattg
     7081 agggtctgac atcctgcccc aaggagtagc taaagtaatt gctagtgttt tcagggattt
     7141 taacatcaga ctggaatgaa tgaatgaaac tttttgtcct ttttttttct gttttttttt
     7201 ttctaatgta gtaaggacta aggaaaacct ttggtgaaga caatcatttc tctctgttga
     7261 tgtggatact tttcacaccg tttatttaaa tgctttctca ataggtccag agccagtgtt
     7321 cttgttcaac ctgaaagtaa tggctctggg ttgggccaga cagttgcact ctctagtttg
     7381 ccctctgcca caaatttgat gtgtgacctt tgggcaagtc atttatcttc tctgggcctt
     7441 agttgcctca tctgtaaaat gagggagttg gagtagatta attattccag ctctgaaatt
     7501 ctaagtgacc ttggctacct tgcagcagtt ttggatttct tccttatctt tgttctgctg
     7561 tttgaggggg ctttttactt atttccatgt tattcaaagg agactaggct tgatatttta
     7621 ttactgttct tttatggaca aaaggttaca tagtatgccc ttaagactta attttaacca
     7681 aaggcctagc accaccttag gggctgcaat aaacacttaa cgcgcgtgcg cacgcgcgcg
     7741 cgcacacaca cacacacaca cacacacaca cacaggtcag agtttaaggc tttcgagtca
     7801 tgacattcta gcttttgaat tgcgtgcaca cacacacgca cgcacacact ctggtcagag
     7861 tttattaagg ctttcgagtc atgacattat agcttttgag ttggtgtgtg tgacaccacc
     7921 ctcctaagtg gtgtgtgctt gtaatttttt ttttcagtga aaatggattg aaaacctgtt
     7981 gttaatgctt agtgatatta tgctcaaaac aaggaaattc ccttgaaccg tgtcaattaa
     8041 actggtttat atgactcaag aaaacaatac cagtagatga ttattaactt tattcttggc
     8101 tctttttagg tccattttga ttaagtgact tttggctgga tcattcagag ctctcttcta
     8161 gcctaccctt ggatgagtac aattaatgaa attcatattt tcaaggacct gggagccttc
     8221 cttggggctg ggttgagggt ggggggttgg ggagtcctgg tagaggccag ctttgtggta
     8281 gctggagagg aagggatgaa accagctgct gttgcaaagg ctgcttgtca ttgatagaag
     8341 gactcacggg cttggattga ttaagactaa acatggagtt ggcaaacttt cttcaagtat
     8401 tgagttctgt tcaatgcatt ggacatgtga tttaagggaa aagtgtgaat gcttatagat
     8461 gatgaaaacc tggtgggctg cagagcccag tttagaagaa gtgagttggg ggttggggac
     8521 agatttggtg gtggtatttc ccaactgttt cctcccctaa attcagagga atgcagctat
     8581 gccagaagcc agagaagagc cactcgtagc ttctgctttg gggacaactg gtcagttgaa
     8641 agtcccagga gttcctttgt ggctttctgt atacttttgc ctggttaaag tctgtggcta
     8701 aaaaatagtc gaacctttct tgagaactct gtaacaaagt atgtttttga ttaaaagaga
     8761 aagccaacta aa
//
