LOCUS       NM_012433               6463 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens splicing factor 3b subunit 1 (SF3B1), transcript
            variant 1, mRNA.
ACCESSION   NM_012433
VERSION     NM_012433.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 6463)
  AUTHORS   Hagerstrand,D., Oder,B., Cortese,D., Qu,Y., Binzer-Panchal,A.,
            Osterholm,C., Del Peso Santos,T., Rabbani,L., Asl,H.F.,
            Skaftason,A., Ljungstrom,V., Lundholm,A., Koutroumani,M.,
            Haider,Z., Jylha,C., Mollstedt,J., Mansouri,L., Plevova,K.,
            Agathangelidis,A., Scarfo,L., Armand,M., Muggen,A.F., Kay,N.E.,
            Shanafelt,T., Rossi,D., Orre,L.M., Pospisilova,S., Barylyuk,K.,
            Davi,F., Vesterlund,M., Langerak,A.W., Lehtio,J., Ghia,P.,
            Stamatopoulos,K., Sutton,L.A. and Rosenquist,R.
  TITLE     The non-canonical BAF chromatin remodeling complex is a novel
            target of spliceosome dysregulation in SF3B1-mutated chronic
            lymphocytic leukemia
  JOURNAL   Leukemia 38 (11), 2429-2442 (2024)
   PUBMED   39261602
  REMARK    GeneRIF: The non-canonical BAF chromatin remodeling complex is a
            novel target of spliceosome dysregulation in SF3B1-mutated chronic
            lymphocytic leukemia.
REFERENCE   2  (bases 1 to 6463)
  AUTHORS   Guo,Y., Wang,X., Du,Y., Zhao,Y., Gao,L., Hao,Y., Lv,D., Feng,X.,
            Zhai,Y., Zou,B., Han,J., Xu,E., Yang,Y., Yang,B., Xi,Y. and
            Zhang,L.
  TITLE     The splicing factor SF3B1 confers ferroptosis resistance and
            promotes lung adenocarcinoma progression via upregulation of
            SLC7A11
  JOURNAL   Cancer Gene Ther 31 (10), 1498-1510 (2024)
   PUBMED   39127833
  REMARK    GeneRIF: The splicing factor SF3B1 confers ferroptosis resistance
            and promotes lung adenocarcinoma progression via upregulation of
            SLC7A11.
REFERENCE   3  (bases 1 to 6463)
  AUTHORS   Winter,S., Schneider,M., Oelschlaegel,U., Maggioni,G., Riva,E.,
            Raddi,M.G., Bencini,S., Peruzzi,B., Choy,D., Antunes Dos Reis,R.,
            Guse,E., Lischer,C., Vera,J., Timms,J.A., Sompairac,N., Sockel,K.,
            Poloni,A., Tunger,A., Della Porta,M.G., Santini,V., Schmitz,M.,
            Platzbecker,U. and Kordasti,S.
  TITLE     Mutations in the splicing factor SF3B1 are linked to frequent
            emergence of HLA-DRlow/neg monocytes in lower-risk myelodysplastic
            neoplasms
  JOURNAL   Leukemia 38 (6), 1427-1431 (2024)
   PUBMED   38632316
  REMARK    GeneRIF: Mutations in the splicing factor SF3B1 are linked to
            frequent emergence of HLA-DR[low/neg] monocytes in lower-risk
            myelodysplastic neoplasms.
REFERENCE   4  (bases 1 to 6463)
  AUTHORS   Benbarche,S., Pineda,J.M.B., Galvis,L.B., Biswas,J., Liu,B.,
            Wang,E., Zhang,Q., Hogg,S.J., Lyttle,K., Dahi,A., Lewis,A.M.,
            Sarchi,M., Rahman,J., Fox,N., Ai,Y., Mehta,S., Garippa,R.,
            Ortiz-Pacheco,J., Li,Z., Monetti,M., Stanley,R.F., Doulatov,S.,
            Bradley,R.K. and Abdel-Wahab,O.
  TITLE     GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in
            hematologic malignancies
  JOURNAL   Mol Cell 84 (10), 1886-1903 (2024)
   PUBMED   38688280
  REMARK    GeneRIF: GPATCH8 modulates mutant SF3B1 mis-splicing and
            pathogenicity in hematologic malignancies.
REFERENCE   5  (bases 1 to 6463)
  AUTHORS   Boddu,P.C., Gupta,A.K., Roy,R., De La Pena Avalos,B.,
            Olazabal-Herrero,A., Neuenkirchen,N., Zimmer,J.T., Chandhok,N.S.,
            King,D., Nannya,Y., Ogawa,S., Lin,H., Simon,M.D., Dray,E.,
            Kupfer,G.M., Verma,A., Neugebauer,K.M. and Pillai,M.M.
  TITLE     Transcription elongation defects link oncogenic SF3B1 mutations to
            targetable alterations in chromatin landscape
  JOURNAL   Mol Cell 84 (8), 1475-1495 (2024)
   PUBMED   38521065
  REMARK    GeneRIF: Transcription elongation defects link oncogenic SF3B1
            mutations to targetable alterations in chromatin landscape.
REFERENCE   6  (bases 1 to 6463)
  AUTHORS   Will,C.L., Schneider,C., MacMillan,A.M., Katopodis,N.F.,
            Neubauer,G., Wilm,M., Luhrmann,R. and Query,C.C.
  TITLE     A novel U2 and U11/U12 snRNP protein that associates with the
            pre-mRNA branch site
  JOURNAL   EMBO J 20 (16), 4536-4546 (2001)
   PUBMED   11500380
REFERENCE   7  (bases 1 to 6463)
  AUTHORS   Isono,K., Abe,K., Tomaru,Y., Okazaki,Y., Hayashizaki,Y. and
            Koseki,H.
  TITLE     Molecular cloning, genetic mapping, and expression of the mouse
            Sf3b1 (SAP155) gene for the U2 snRNP component of spliceosome
  JOURNAL   Mamm Genome 12 (3), 192-198 (2001)
   PUBMED   11252167
REFERENCE   8  (bases 1 to 6463)
  AUTHORS   Das,R., Zhou,Z. and Reed,R.
  TITLE     Functional association of U2 snRNP with the ATP-independent
            spliceosomal complex E
  JOURNAL   Mol Cell 5 (5), 779-787 (2000)
   PUBMED   10882114
REFERENCE   9  (bases 1 to 6463)
  AUTHORS   Pauling,M.H., McPheeters,D.S. and Ares,M. Jr.
  TITLE     Functional Cus1p is found with Hsh155p in a multiprotein splicing
            factor associated with U2 snRNA
  JOURNAL   Mol Cell Biol 20 (6), 2176-2185 (2000)
   PUBMED   10688664
REFERENCE   10 (bases 1 to 6463)
  AUTHORS   Wang,C., Chua,K., Seghezzi,W., Lees,E., Gozani,O. and Reed,R.
  TITLE     Phosphorylation of spliceosomal protein SAP 155 coupled with
            splicing catalysis
  JOURNAL   Genes Dev 12 (10), 1409-1414 (1998)
   PUBMED   9585501
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK294851.1, BC039020.1,
            AF054284.1, BE168209.1, AF070540.1 and AC010746.8.
            
            On Nov 21, 2019 this sequence version replaced NM_012433.3.
            
            Summary: This gene encodes subunit 1 of the splicing factor 3b
            protein complex. Splicing factor 3b, together with splicing factor
            3a and a 12S RNA unit, forms the U2 small nuclear
            ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a
            complex binds pre-mRNA upstream of the intron's branch site in a
            sequence independent manner and may anchor the U2 snRNP to the
            pre-mRNA. Splicing factor 3b is also a component of the minor
            U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1
            have 22 non-identical, tandem HEAT repeats that form rod-like,
            helical structures. Alternative splicing results in multiple
            transcript variants encoding different isoforms. [provided by
            RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (1).
            
            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 :: SRR11853559.19693.1,
                                           SRR1660805.250476.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000335508.11/ ENSP00000335321.6
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-444               AK294851.1         52-495
            445-2388            BC039020.1         433-2376
            2389-2659           AF054284.1         2360-2630
            2660-2929           BE168209.1         12-281              c
            2930-4032           AF054284.1         2901-4003
            4033-4273           AF070540.1         976-1216
            4274-6463           AC010746.8         125400-127589       c
FEATURES             Location/Qualifiers
     source          1..6463
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q33.1"
     gene            1..6463
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /note="splicing factor 3b subunit 1"
                     /db_xref="GeneID:23451"
                     /db_xref="HGNC:HGNC:10768"
                     /db_xref="MIM:605590"
     exon            1..57
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     CDS             30..3944
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /note="isoform 1 is encoded by transcript variant 1;
                     pre-mRNA splicing factor SF3b, 155 kDa subunit; pre-mRNA
                     processing 10; spliceosome-associated protein 155;
                     splicing factor 3b, subunit 1, 155kDa"
                     /codon_start=1
                     /product="splicing factor 3B subunit 1 isoform 1"
                     /protein_id="NP_036565.2"
                     /db_xref="CCDS:CCDS33356.1"
                     /db_xref="GeneID:23451"
                     /db_xref="HGNC:HGNC:10768"
                     /db_xref="MIM:605590"
                     /translation="MAKIAKTHEDIEAQIREIQGKKAALDEAQGVGLDSTGYYDQEIY
                     GGSDSRFAGYVTSIAATELEDDDDDYSSSTSLLGQKKPGYHAPVALLNDIPQSTEQYD
                     PFAEHRPPKIADREDEYKKHRRTMIISPERLDPFADGGKTPDPKMNARTYMDVMREQH
                     LTKEEREIRQQLAEKAKAGELKVVNGAAASQPPSKRKRRWDQTADQTPGATPKKLSSW
                     DQAETPGHTPSLRWDETPGRAKGSETPGATPGSKIWDPTPSHTPAGAATPGRGDTPGH
                     ATPGHGGATSSARKNRWDETPKTERDTPGHGSGWAETPRTDRGGDSIGETPTPGASKR
                     KSRWDETPASQMGGSTPVLTPGKTPIGTPAMNMATPTPGHIMSMTPEQLQAWRWEREI
                     DERNRPLSDEELDAMFPEGYKVLPPPAGYVPIRTPARKLTATPTPLGGMTGFHMQTED
                     RTMKSVNDQPSGNLPFLKPDDIQYFDKLLVDVDESTLSPEEQKERKIMKLLLKIKNGT
                     PPMRKAALRQITDKAREFGAGPLFNQILPLLMSPTLEDQERHLLVKVIDRILYKLDDL
                     VRPYVHKILVVIEPLLIDEDYYARVEGREIISNLAKAAGLATMISTMRPDIDNMDEYV
                     RNTTARAFAVVASALGIPSLLPFLKAVCKSKKSWQARHTGIKIVQQIAILMGCAILPH
                     LRSLVEIIEHGLVDEQQKVRTISALAIAALAEAATPYGIESFDSVLKPLWKGIRQHRG
                     KGLAAFLKAIGYLIPLMDAEYANYYTREVMLILIREFQSPDEEMKKIVLKVVKQCCGT
                     DGVEANYIKTEILPPFFKHFWQHRMALDRRNYRQLVDTTVELANKVGAAEIISRIVDD
                     LKDEAEQYRKMVMETIEKIMGNLGAADIDHKLEEQLIDGILYAFQEQTTEDSVMLNGF
                     GTVVNALGKRVKPYLPQICGTVLWRLNNKSAKVRQQAADLISRTAVVMKTCQEEKLMG
                     HLGVVLYEYLGEEYPEVLGSILGALKAIVNVIGMHKMTPPIKDLLPRLTPILKNRHEK
                     VQENCIDLVGRIADRGAEYVSAREWMRICFELLELLKAHKKAIRRATVNTFGYIAKAI
                     GPHDVLATLLNNLKVQERQNRVCTTVAIAIVAETCSPFTVLPALMNEYRVPELNVQNG
                     VLKSLSFLFEYIGEMGKDYIYAVTPLLEDALMDRDLVHRQTASAVVQHMSLGVYGFGC
                     EDSLNHLLNYVWPNVFETSPHVIQAVMGALEGLRVAIGPCRMLQYCLQGLFHPARKVR
                     DVYWKIYNSIYIGSQDALIAHYPRIYNDDKNTYIRYELDYIL"
     exon            58..224
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            225..329
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            330..444
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            445..524
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            525..695
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            696..933
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            934..1146
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            1147..1268
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            1269..1466
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            1467..1568
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            1569..1748
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            1749..1835
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            1836..2106
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            2107..2252
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            2253..2399
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            2400..2525
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            2526..2747
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            2748..2930
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            2931..3042
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            3043..3163
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            3164..3295
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            3296..3568
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            3569..3785
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     exon            3786..6463
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4247..4252
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /note="hexamer: AATAAA"
     polyA_site      4273
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /note="major polyA site"
     regulatory      4395..4400
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /note="hexamer: AATAAA"
     polyA_site      4415
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
     regulatory      6442..6447
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
                     /note="hexamer: AATAAA"
     polyA_site      6463
                     /gene="SF3B1"
                     /gene_synonym="Hsh155; MDS; PRP10; PRPF10; SAP155;
                     SF3b155"
ORIGIN      
        1 agttccgtct gtgtgttcga gtggacaaaa tggcgaagat cgccaagact cacgaagata
       61 ttgaagcaca gattcgagaa attcaaggca agaaggcagc tcttgatgaa gctcaaggag
      121 tgggcctcga ttctacaggt tattatgacc aggaaattta tggtggaagt gacagcagat
      181 ttgctggata cgtgacatca attgctgcaa ctgaacttga agatgatgac gatgactatt
      241 catcatctac gagtttgctt ggtcagaaga agccaggata tcatgcccct gtggcattgc
      301 ttaatgatat accacagtca acagaacagt atgatccatt tgctgagcac agacctccaa
      361 agattgcaga ccgggaagat gaatacaaaa agcataggcg gaccatgata atttccccag
      421 agcgtcttga tccttttgca gatggaggga aaacccctga tcctaaaatg aatgctagga
      481 cttacatgga tgtaatgcga gaacaacact tgactaaaga agaacgagaa attaggcaac
      541 agctagcaga aaaagctaaa gctggagaac taaaagtcgt caatggagca gcagcgtccc
      601 agcctccatc aaaacgaaaa cggcgttggg atcaaacagc tgatcagact cctggtgcca
      661 ctcccaaaaa actatcaagt tgggatcagg cagagacccc tgggcatact ccttccttaa
      721 gatgggatga gacaccaggt cgtgcaaagg gaagcgagac tcctggagca accccaggct
      781 caaaaatatg ggatcctaca cctagccaca caccagcggg agctgctact cctggacgag
      841 gtgatacacc aggccatgcg acaccaggcc atggaggcgc aacttccagt gctcgtaaaa
      901 acagatggga tgaaaccccc aaaacagaga gagatactcc tgggcatgga agtggatggg
      961 ctgagactcc tcgaacagat cgaggtggag attctattgg tgaaacaccg actcctggag
     1021 ccagtaaaag aaaatcacgg tgggatgaaa caccagctag tcagatgggt ggaagcactc
     1081 cagttctgac ccctggaaag acaccaattg gcacaccagc catgaacatg gctaccccta
     1141 ctccaggtca cataatgagt atgactcctg aacagcttca ggcttggcgg tgggaaagag
     1201 aaattgatga gagaaatcgc ccactttctg atgaggaatt agatgctatg ttcccagaag
     1261 gatataaggt acttcctcct ccagctggtt atgttcctat tcgaactcca gctcgaaagc
     1321 tgacagctac tccaacacct ttgggtggta tgactggttt ccacatgcaa actgaagatc
     1381 gaactatgaa aagtgttaat gaccagccat ctggaaatct tccattttta aaacctgatg
     1441 atattcaata ctttgataaa ctattggttg atgttgatga atcaacactt agtccagaag
     1501 agcaaaaaga gagaaaaata atgaagttgc ttttaaaaat taagaatgga acaccaccaa
     1561 tgagaaaggc tgcattgcgt cagattactg ataaagctcg tgaatttgga gctggtcctt
     1621 tgtttaatca gattcttcct ctgctgatgt ctcctacact tgaggatcaa gagcgtcatt
     1681 tacttgtgaa agttattgat aggatactgt acaaacttga tgacttagtt cgtccatatg
     1741 tgcataagat cctcgtggtc attgaaccgc tattgattga tgaagattac tatgctagag
     1801 tggaaggccg agagatcatt tctaatttgg caaaggctgc tggtctggct actatgatct
     1861 ctaccatgag acctgatata gataacatgg atgagtatgt ccgtaacaca acagctagag
     1921 cttttgctgt tgtagcctct gccctgggca ttccttcttt attgcccttc ttaaaagctg
     1981 tgtgcaaaag caagaagtcc tggcaagcga gacacactgg tattaagatt gtacaacaga
     2041 tagctattct tatgggctgt gccatcttgc cacatcttag aagtttagtt gaaatcattg
     2101 aacatggtct tgtggatgag cagcagaaag ttcggaccat cagtgctttg gccattgctg
     2161 ccttggctga agcagcaact ccttatggta tcgaatcttt tgattctgtg ttaaagcctt
     2221 tatggaaggg tatccgccaa cacagaggaa agggtttggc tgctttcttg aaggctattg
     2281 ggtatcttat tcctcttatg gatgcagaat atgccaacta ctatactaga gaagtgatgt
     2341 taatccttat tcgagaattc cagtctcctg atgaggaaat gaaaaaaatt gtgctgaagg
     2401 tggtaaaaca gtgttgtggg acagatggtg tagaagcaaa ctacattaaa acagagattc
     2461 ttcctccctt ttttaaacac ttctggcagc acaggatggc tttggataga agaaattacc
     2521 gacagttagt tgatactact gtggagttgg caaacaaagt aggtgcagca gaaattatat
     2581 ccaggattgt ggatgatctg aaagatgaag ccgaacagta cagaaaaatg gtgatggaga
     2641 caattgagaa aattatgggt aatttgggag cagcagatat tgatcataaa cttgaagaac
     2701 aactgattga tggtattctt tatgctttcc aagaacagac tacagaggac tcagtaatgt
     2761 tgaacggctt tggcacagtg gttaatgctc ttggcaaacg agtcaaacca tacttgcctc
     2821 agatctgtgg tacagttttg tggcgtttaa ataacaaatc tgctaaagtt aggcaacagg
     2881 cagctgactt gatttctcga actgctgttg tcatgaagac ttgtcaagag gaaaaattga
     2941 tgggacactt gggtgttgta ttgtatgagt atttgggtga agagtaccct gaagtattgg
     3001 gcagcattct tggagcactg aaggccattg taaatgtcat aggtatgcat aagatgactc
     3061 caccaattaa agatctgctg cctagactca cccccatctt aaagaacaga catgaaaaag
     3121 tacaagagaa ttgtattgat cttgttggtc gtattgctga caggggagct gaatatgtat
     3181 ctgcaagaga gtggatgagg atttgctttg agcttttaga gctcttaaaa gcccacaaaa
     3241 aggctattcg tagagccaca gtcaacacat ttggttatat tgcaaaggcc attggccctc
     3301 atgatgtatt ggctacactt ctgaacaacc tcaaagttca agaaaggcag aacagagttt
     3361 gtaccactgt agcaatagct attgttgcag aaacatgttc accctttaca gtactccctg
     3421 ccttaatgaa tgaatacaga gttcctgaac tgaatgttca aaatggagtg ttaaaatcgc
     3481 tttccttctt gtttgaatat attggtgaaa tgggaaaaga ctacatttat gccgtaacac
     3541 cgttacttga agatgcttta atggatagag accttgtaca cagacagacg gctagtgcag
     3601 tggtacagca catgtcactt ggggtttatg gatttggttg tgaagattcg ctgaatcact
     3661 tgttgaacta tgtatggccc aatgtatttg agacatctcc tcatgtaatt caggcagtta
     3721 tgggagccct agagggcctg agagttgcta ttggaccatg tagaatgttg caatattgtt
     3781 tacagggtct gtttcaccca gcccggaaag tcagagatgt atattggaaa atttacaact
     3841 ccatctacat tggttcccag gacgctctca tagcacatta cccaagaatc tacaacgatg
     3901 ataagaacac ctatattcgt tatgaacttg actatatctt ataattttat tgtttatttt
     3961 gtgtttaatg cacagctact tcacacctta aacttgcttt gatttggtga tgtaaacttt
     4021 taaacattgc agatcagtgt agaactggtc atagaggaag agctagaaat ccagtagcat
     4081 gatttttaaa taacctgtct ttgtttttga tgttaaacag taaatgccag tagtgaccaa
     4141 gaacacagtg attatataca ctatactgga gggatttcat ttttaattca tctttatgaa
     4201 gatttagaac tcattccttg tgtttaaagg gaatgtttaa ttgagaaata aacatttgtg
     4261 tacaaaatgc taatttgtgt gtgttttttg aacatgactt gtaaaatgcg gaactttgat
     4321 aaagtattgg tttatgtgga ataagtggct taatttcatt ttctgtcaca tggtttatag
     4381 aaagtagtta gctgaataaa aactatataa agtgatggca tctttgtcaa aattccattg
     4441 ttgtgttaat aatgacagca agaagagtag cctcagggga tgttcccctc aaactagcac
     4501 aaccattcca tcatcgtaga aaagtagcac ttttgctaaa ctgtcttgaa tattttgtac
     4561 ttacatagcg cctttcatct cttgatttct caaaatgctt tatgaacaca tttaaagaaa
     4621 gtggtttaag tcttgtccaa cacttgacag gtctgctgtg tttagcaagt gaggaattta
     4681 actttacttc aaaactgctt tctgcctatt aggagtgagg atacctaagt aatgctgata
     4741 gaacaggaca atgttgggct tttctccatg ttataagcca ctactcagca atgcatcagt
     4801 aaatacctat tcacccactg tatgccagcc actgtgctta tatgcagggg atgcaaaggt
     4861 gcatgagacc tgccctctac ctttaagaac agtataatgg agaaggggag acaaaccttg
     4921 tgacagattc cttatgtact gtgataatac acagtggcag cagctaaaat gtctaggttt
     4981 gcttagcttt gtattcagta ataataagtt gatctaagag ttcagcataa actgaatgaa
     5041 atgccattta atggtagagg aaccaagcat taaggcagta ctacacttaa ttttttaagc
     5101 aaatatgtaa agtatatttt caaacttttc taatgttatg gccccaaatt tcttagtttt
     5161 ggccttttta ctacctatac tatttttact gttttgtttt gtctccatgt ggtagtactt
     5221 ctgtgaactc taaagggaaa aaaaattctg caagcagcat tagtatataa ctactactgt
     5281 aagtaaaact gcctattgac actttaggag ttcctgcttc agaagcttag ttaagaaaca
     5341 gcttgtggcc gggtgtggtg gctcatgcct gtaatcccag cactttggga ggctgaggcg
     5401 ggcggatcac gaggtcagga gatcgagacc atcctggcta acgcggtgaa gtcccgtcta
     5461 ctaaaaatac aaaaattagc caggcgtggt ggcgggcgcc tgtagtccca gctactaggg
     5521 aggctgaggc aggagaatgg cttgaacccg ggaggcggag cttgcagtga gccgagatag
     5581 cgctgctaca ctccagcctg ggcgacagag actccgtctc aaaaaaaaaa aaaaaattga
     5641 ctttcaacaa attgatagtg agcattaagg gtttccaagt tggatttgta actcctcatc
     5701 attccttgta tgacaacttt ctgaatatat gtcactatgt agtaaaatta aacactccaa
     5761 actcatcttt ctgttgttag aagttttcag cggtacttcc atgcaacttt aaatctcact
     5821 gctctctatg gttgatgtca aatgaccttc agtaatgact gagaattgaa tacaaataga
     5881 ttacaaagcc aaaatttgat gttaaatgac tcaggaaatt ttagttgtat tttcaattca
     5941 agtacttagt agcctacgtt tgcttggcct ctggttcttt atggaaaata ggctttgtag
     6001 tggcattgtg gagcaaagga gactgttaca ccttaattaa ctttttttac tgatgcaaat
     6061 aatttgagga tagagaggag ggaagtagtg aaagctatga cctaaaacat tgggaccaaa
     6121 tagaggctca cagatatttg gattatttta tgtgcttatt attaaataag gaaagcattt
     6181 tgtgatatgt ggaagacgct atgtgaagtt ttacctatct tctcaaagac cttttctttt
     6241 gtattttctt ttggtgtttc ttaaagccaa acaaagaaat gttcttaagg agacagggtg
     6301 ggtttttctg tgggcctttg ttggtttttc tgtgggccat cgccctctaa tggaattgat
     6361 ctctggctgt ttgatttttt tcatattgta tttttaaaat ttgttgtaca gtgccctgtg
     6421 agcaccaagt accactagat gaataaaacg tattatatct aaa
//
