LOCUS       NM_000038              10704 bp    mRNA    linear   PRI 18-NOV-2024
DEFINITION  Homo sapiens APC regulator of WNT signaling pathway (APC),
            transcript variant 3, mRNA.
ACCESSION   NM_000038
VERSION     NM_000038.6
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 10704)
  AUTHORS   Song,J., Ke,B. and Fang,X.
  TITLE     APC and ZBTB2 May Mediate M2 Macrophage Infiltration to Promote the
            Development of Renal Fibrosis: A Bioinformatics Analysis
  JOURNAL   Biomed Res Int 2024, 5674711 (2024)
   PUBMED   39328595
  REMARK    GeneRIF: APC and ZBTB2 May Mediate M2 Macrophage Infiltration to
            Promote the Development of Renal Fibrosis: A Bioinformatics
            Analysis.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 10704)
  AUTHORS   Kliche,J., Simonetti,L., Krystkowiak,I., Kuss,H., Diallo,M.,
            Rask,E., Nilsson,J., Davey,N.E. and Ivarsson,Y.
  TITLE     Proteome-scale characterisation of motif-based interactome rewiring
            by disease mutations
  JOURNAL   Mol Syst Biol 20 (9), 1025-1048 (2024)
   PUBMED   39009827
REFERENCE   3  (bases 1 to 10704)
  AUTHORS   Arteaga-Blanco,L.A., Evans,A.E. and Dixon,D.A.
  TITLE     Plasma-Derived Extracellular Vesicles and Non-Extracellular Vesicle
            Components from APCMin/+ Mice Promote Pro-Tumorigenic Activities
            and Activate Human Colonic Fibroblasts via the NF-kappaB Signaling
            Pathway
  JOURNAL   Cells 13 (14), 1195 (2024)
   PUBMED   39056778
  REMARK    GeneRIF: Plasma-Derived Extracellular Vesicles and
            Non-Extracellular Vesicle Components from APC[Min/+] Mice Promote
            Pro-Tumorigenic Activities and Activate Human Colonic Fibroblasts
            via the NF-kappaB Signaling Pathway.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 10704)
  AUTHORS   Lambertz,S. and Ballhausen,W.G.
  TITLE     Identification of an alternative 5' untranslated region of the
            adenomatous polyposis coli gene
  JOURNAL   Hum Genet 90 (6), 650-652 (1993)
   PUBMED   8383094
REFERENCE   5  (bases 1 to 10704)
  AUTHORS   Yen,T., Stanich,P.P., Axell,L. and Patel,S.G.
  TITLE     APC-Associated Polyposis Conditions
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301519
REFERENCE   6  (bases 1 to 10704)
  AUTHORS   Nakatsuru,S., Yanagisawa,A., Ichii,S., Tahara,E., Kato,Y.,
            Nakamura,Y. and Horii,A.
  TITLE     Somatic mutation of the APC gene in gastric cancer: frequent
            mutations in very well differentiated adenocarcinoma and
            signet-ring cell carcinoma
  JOURNAL   Hum Mol Genet 1 (8), 559-563 (1992)
   PUBMED   1338691
REFERENCE   7  (bases 1 to 10704)
  AUTHORS   Miki,Y., Nishisho,I., Horii,A., Miyoshi,Y., Utsunomiya,J.,
            Kinzler,K.W., Vogelstein,B. and Nakamura,Y.
  TITLE     Disruption of the APC gene by a retrotransposal insertion of L1
            sequence in a colon cancer
  JOURNAL   Cancer Res 52 (3), 643-645 (1992)
   PUBMED   1310068
REFERENCE   8  (bases 1 to 10704)
  AUTHORS   Nagase,H., Miyoshi,Y., Horii,A., Aoki,T., Petersen,G.M.,
            Vogelstein,B., Maher,E., Ogawa,M., Maruyama,M., Utsunomiya,J. et
            al.
  TITLE     Screening for germ-line mutations in familial adenomatous polyposis
            patients: 61 new patients and a summary of 150 unrelated patients
  JOURNAL   Hum Mutat 1 (6), 467-473 (1992)
   PUBMED   1338764
REFERENCE   9  (bases 1 to 10704)
  AUTHORS   Nishisho,I., Nakamura,Y., Miyoshi,Y., Miki,Y., Ando,H., Horii,A.,
            Koyama,K., Utsunomiya,J., Baba,S. and Hedge,P.
  TITLE     Mutations of chromosome 5q21 genes in FAP and colorectal cancer
            patients
  JOURNAL   Science 253 (5020), 665-669 (1991)
   PUBMED   1651563
REFERENCE   10 (bases 1 to 10704)
  AUTHORS   Kinzler,K.W., Nilbert,M.C., Su,L.K., Vogelstein,B., Bryan,T.M.,
            Levy,D.B., Smith,K.J., Preisinger,A.C., Hedge,P., McKechnie,D. et
            al.
  TITLE     Identification of FAP locus genes from chromosome 5q21
  JOURNAL   Science 253 (5020), 661-665 (1991)
   PUBMED   1651562
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA795663.1, M73548.1,
            AB210001.1 and CA313732.1.
            
            On Nov 22, 2018 this sequence version replaced NM_000038.5.
            
            Summary: This gene encodes a tumor suppressor protein that acts as
            an antagonist of the Wnt signaling pathway. It is also involved in
            other processes including cell migration and adhesion,
            transcriptional activation, and apoptosis. Defects in this gene
            cause familial adenomatous polyposis (FAP), an autosomal dominant
            pre-malignant disease that usually progresses to malignancy.
            Mutations in the APC gene have been found to occur in most
            colorectal cancers, where disease-associated mutations tend to be
            clustered in a small region designated the mutation cluster region
            (MCR) and result in a truncated protein product. [provided by
            RefSeq, Jun 2022].
            
            Transcript Variant: This variant (3) differs in the 5' UTR, lacks a
            portion of the 5' coding region, and initiates translation at an
            alternate start codon, compared to variant 1. This variant also
            contains an alternate in-frame exon compared to variant 1. The
            encoded isoform (b) has a distinct N-terminus and is longer than
            isoform a. Variants 2, 3, and 4 all encode the same isoform (b).
            
            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 :: SRR1803613.217786.1, M73548.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000257430.9/ ENSP00000257430.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-40                DA795663.1         27-66
            41-608              M73548.1           20-587
            609-10521           AB210001.1         707-10619
            10522-10704         CA313732.1         18-200              c
FEATURES             Location/Qualifiers
     source          1..10704
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5q22.2"
     gene            1..10704
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /note="APC regulator of WNT signaling pathway"
                     /db_xref="GeneID:324"
                     /db_xref="HGNC:HGNC:583"
                     /db_xref="MIM:611731"
     exon            1..41
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            42..194
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     CDS             60..8591
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /note="isoform b is encoded by transcript variant 3;
                     adenomatous polyposis coli protein; WNT signaling pathway
                     regulator; adenomatosis polyposis coli tumor suppressor;
                     deleted in polyposis 2.5; protein phosphatase 1,
                     regulatory subunit 46; adenomatous polyposis coli (APC);
                     epididymis secretory sperm binding protein; APC, WNT
                     signaling pathway regulator"
                     /codon_start=1
                     /product="adenomatous polyposis coli protein isoform b"
                     /protein_id="NP_000029.2"
                     /db_xref="CCDS:CCDS4107.1"
                     /db_xref="GeneID:324"
                     /db_xref="HGNC:HGNC:583"
                     /db_xref="MIM:611731"
                     /translation="MAAASYDQLLKQVEALKMENSNLRQELEDNSNHLTKLETEASNM
                     KEVLKQLQGSIEDEAMASSGQIDLLERLKELNLDSSNFPGVKLRSKMSLRSYGSREGS
                     VSSRSGECSPVPMGSFPRRGFVNGSRESTGYLEELEKERSLLLADLDKEEKEKDWYYA
                     QLQNLTKRIDSLPLTENFSLQTDMTRRQLEYEARQIRVAMEEQLGTCQDMEKRAQRRI
                     ARIQQIEKDILRIRQLLQSQATEAERSSQNKHETGSHDAERQNEGQGVGEINMATSGN
                     GQGSTTRMDHETASVLSSSSTHSAPRRLTSHLGTKVEMVYSLLSMLGTHDKDDMSRTL
                     LAMSSSQDSCISMRQSGCLPLLIQLLHGNDKDSVLLGNSRGSKEARARASAALHNIIH
                     SQPDDKRGRREIRVLHLLEQIRAYCETCWEWQEAHEPGMDQDKNPMPAPVEHQICPAV
                     CVLMKLSFDEEHRHAMNELGGLQAIAELLQVDCEMYGLTNDHYSITLRRYAGMALTNL
                     TFGDVANKATLCSMKGCMRALVAQLKSESEDLQQVIASVLRNLSWRADVNSKKTLREV
                     GSVKALMECALEVKKESTLKSVLSALWNLSAHCTENKADICAVDGALAFLVGTLTYRS
                     QTNTLAIIESGGGILRNVSSLIATNEDHRQILRENNCLQTLLQHLKSHSLTIVSNACG
                     TLWNLSARNPKDQEALWDMGAVSMLKNLIHSKHKMIAMGSAAALRNLMANRPAKYKDA
                     NIMSPGSSLPSLHVRKQKALEAELDAQHLSETFDNIDNLSPKASHRSKQRHKQSLYGD
                     YVFDTNRHDDNRSDNFNTGNMTVLSPYLNTTVLPSSSSSRGSLDSSRSEKDRSLERER
                     GIGLGNYHPATENPGTSSKRGLQISTTAAQIAKVMEEVSAIHTSQEDRSSGSTTELHC
                     VTDERNALRRSSAAHTHSNTYNFTKSENSNRTCSMPYAKLEYKRSSNDSLNSVSSSDG
                     YGKRGQMKPSIESYSEDDESKFCSYGQYPADLAHKIHSANHMDDNDGELDTPINYSLK
                     YSDEQLNSGRQSPSQNERWARPKHIIEDEIKQSEQRQSRNQSTTYPVYTESTDDKHLK
                     FQPHFGQQECVSPYRSRGANGSETNRVGSNHGINQNVSQSLCQEDDYEDDKPTNYSER
                     YSEEEQHEEEERPTNYSIKYNEEKRHVDQPIDYSLKYATDIPSSQKQSFSFSKSSSGQ
                     SSKTEHMSSSSENTSTPSSNAKRQNQLHPSSAQSRSGQPQKAATCKVSSINQETIQTY
                     CVEDTPICFSRCSSLSSLSSAEDEIGCNQTTQEADSANTLQIAEIKEKIGTRSAEDPV
                     SEVPAVSQHPRTKSSRLQGSSLSSESARHKAVEFSSGAKSPSKSGAQTPKSPPEHYVQ
                     ETPLMFSRCTSVSSLDSFESRSIASSVQSEPCSGMVSGIISPSDLPDSPGQTMPPSRS
                     KTPPPPPQTAQTKREVPKNKAPTAEKRESGPKQAAVNAAVQRVQVLPDADTLLHFATE
                     STPDGFSCSSSLSALSLDEPFIQKDVELRIMPPVQENDNGNETESEQPKESNENQEKE
                     AEKTIDSEKDLLDDSDDDDIEILEECIISAMPTKSSRKAKKPAQTASKLPPPVARKPS
                     QLPVYKLLPSQNRLQPQKHVSFTPGDDMPRVYCVEGTPINFSTATSLSDLTIESPPNE
                     LAAGEGVRGGAQSGEFEKRDTIPTEGRSTDEAQGGKTSSVTIPELDDNKAEEGDILAE
                     CINSAMPKGKSHKPFRVKKIMDQVQQASASSSAPNKNQLDGKKKKPTSPVKPIPQNTE
                     YRTRVRKNADSKNNLNAERVFSDNKDSKKQNLKNNSKVFNDKLPNNEDRVRGSFAFDS
                     PHHYTPIEGTPYCFSRNDSLSSLDFDDDDVDLSREKAELRKAKENKESEAKVTSHTEL
                     TSNQQSANKTQAIAKQPINRGQPKPILQKQSTFPQSSKDIPDRGAATDEKLQNFAIEN
                     TPVCFSHNSSLSSLSDIDQENNNKENEPIKETEPPDSQGEPSKPQASGYAPKSFHVED
                     TPVCFSRNSSLSSLSIDSEDDLLQECISSAMPKKKKPSRLKGDNEKHSPRNMGGILGE
                     DLTLDLKDIQRPDSEHGLSPDSENFDWKAIQEGANSIVSSLHQAAAAACLSRQASSDS
                     DSILSLKSGISLGSPFHLTPDQEEKPFTSNKGPRILKPGEKSTLETKKIESESKGIKG
                     GKKVYKSLITGKVRSNSEISGQMKQPLQANMPSISRGRTMIHIPGVRNSSSSTSPVSK
                     KGPPLKTPASKSPSEGQTATTSPRGAKPSVKSELSPVARQTSQIGGSSKAPSRSGSRD
                     STPSRPAQQPLSRPIQSPGRNSISPGRNGISPPNKLSQLPRTSSPSTASTKSSGSGKM
                     SYTSPGRQMSQQNLTKQTGLSKNASSIPRSESASKGLNQMNNGNGANKKVELSRMSST
                     KSSGSESDRSERPVLVRQSTFIKEAPSPTLRRKLEESASFESLSPSSRPASPTRSQAQ
                     TPVLSPSLPDMSLSTHSSVQAGGWRKLPPNLSPTIEYNDGRPAKRHDIARSHSESPSR
                     LPINRSGTWKREHSKHSSSLPRVSTWRRTGSSSSILSASSESSEKAKSEDEKHVNSIS
                     GTKQSKENQVSAKGTWRKIKENEFSPTNSTSQTVSSGATNGAESKTLIYQMAPAVSKT
                     EDVWVRIEDCPINNPRSGRSPTGNTPPVIDSVSEKANPNIKDSKDNQAKQNVGNGSVP
                     MRTVGLENRLNSFIQVDAPDQKGTEIKPGQNNPVPVSETNESSIVERTPFSSSSSSKH
                     SSPSGTVAARVTPFNYNPSPRKSSADSTSARPSQIPTPVNNNTKKRDSKTDSTESSGT
                     QSPKRHSGSYLVTSV"
     exon            195..279
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            280..481
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            482..590
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            591..704
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            705..788
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            789..893
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            894..992
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            993..1371
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            1372..1467
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            1468..1607
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            1608..1685
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            1686..1802
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            1803..2017
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     exon            2018..10704
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /inference="alignment:Splign:2.1.0"
     regulatory      9422..9427
                     /regulatory_class="polyA_signal_sequence"
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /note="hexamer: AATAAA"
     polyA_site      9444
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /note="major polyA site"
     regulatory      9584..9589
                     /regulatory_class="polyA_signal_sequence"
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /note="hexamer: AATAAA"
     polyA_site      9618
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
     regulatory      10502..10507
                     /regulatory_class="polyA_signal_sequence"
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /note="hexamer: AATAAA"
     polyA_site      10529
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
     regulatory      10682..10687
                     /regulatory_class="polyA_signal_sequence"
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
                     /note="hexamer: CATAAA"
     polyA_site      10704
                     /gene="APC"
                     /gene_synonym="BTPS2; DESMD; DP2; DP2.5; DP3; GS; PPP1R46"
ORIGIN      
        1 actggagaca gaatggaggt gctgccggac tcggaaatgg ggtccaaggg tagccaagga
       61 tggctgcagc ttcatatgat cagttgttaa agcaagttga ggcactgaag atggagaact
      121 caaatcttcg acaagagcta gaagataatt ccaatcatct tacaaaactg gaaactgagg
      181 catctaatat gaaggaagta cttaaacaac tacaaggaag tattgaagat gaagctatgg
      241 cttcttctgg acagattgat ttattagagc gtcttaaaga gcttaactta gatagcagta
      301 atttccctgg agtaaaactg cggtcaaaaa tgtccctccg ttcttatgga agccgggaag
      361 gatctgtatc aagccgttct ggagagtgca gtcctgttcc tatgggttca tttccaagaa
      421 gagggtttgt aaatggaagc agagaaagta ctggatattt agaagaactt gagaaagaga
      481 ggtcattgct tcttgctgat cttgacaaag aagaaaagga aaaagactgg tattacgctc
      541 aacttcagaa tctcactaaa agaatagata gtcttccttt aactgaaaat ttttccttac
      601 aaacagatat gaccagaagg caattggaat atgaagcaag gcaaatcaga gttgcgatgg
      661 aagaacaact aggtacctgc caggatatgg aaaaacgagc acagcgaaga atagccagaa
      721 ttcagcaaat cgaaaaggac atacttcgta tacgacagct tttacagtcc caagcaacag
      781 aagcagagag gtcatctcag aacaagcatg aaaccggctc acatgatgct gagcggcaga
      841 atgaaggtca aggagtggga gaaatcaaca tggcaacttc tggtaatggt cagggttcaa
      901 ctacacgaat ggaccatgaa acagccagtg ttttgagttc tagtagcaca cactctgcac
      961 ctcgaaggct gacaagtcat ctgggaacca aggtggaaat ggtgtattca ttgttgtcaa
     1021 tgcttggtac tcatgataag gatgatatgt cgcgaacttt gctagctatg tctagctccc
     1081 aagacagctg tatatccatg cgacagtctg gatgtcttcc tctcctcatc cagcttttac
     1141 atggcaatga caaagactct gtattgttgg gaaattcccg gggcagtaaa gaggctcggg
     1201 ccagggccag tgcagcactc cacaacatca ttcactcaca gcctgatgac aagagaggca
     1261 ggcgtgaaat ccgagtcctt catcttttgg aacagatacg cgcttactgt gaaacctgtt
     1321 gggagtggca ggaagctcat gaaccaggca tggaccagga caaaaatcca atgccagctc
     1381 ctgttgaaca tcagatctgt cctgctgtgt gtgttctaat gaaactttca tttgatgaag
     1441 agcatagaca tgcaatgaat gaactagggg gactacaggc cattgcagaa ttattgcaag
     1501 tggactgtga aatgtatggg cttactaatg accactacag tattacacta agacgatatg
     1561 ctggaatggc tttgacaaac ttgacttttg gagatgtagc caacaaggct acgctatgct
     1621 ctatgaaagg ctgcatgaga gcacttgtgg cccaactaaa atctgaaagt gaagacttac
     1681 agcaggttat tgcgagtgtt ttgaggaatt tgtcttggcg agcagatgta aatagtaaaa
     1741 agacgttgcg agaagttgga agtgtgaaag cattgatgga atgtgcttta gaagttaaaa
     1801 aggaatcaac cctcaaaagc gtattgagtg ccttatggaa tttgtcagca cattgcactg
     1861 agaataaagc tgatatatgt gctgtagatg gtgcacttgc atttttggtt ggcactctta
     1921 cttaccggag ccagacaaac actttagcca ttattgaaag tggaggtggg atattacgga
     1981 atgtgtccag cttgatagct acaaatgagg accacaggca aatcctaaga gagaacaact
     2041 gtctacaaac tttattacaa cacttaaaat ctcatagttt gacaatagtc agtaatgcat
     2101 gtggaacttt gtggaatctc tcagcaagaa atcctaaaga ccaggaagca ttatgggaca
     2161 tgggggcagt tagcatgctc aagaacctca ttcattcaaa gcacaaaatg attgctatgg
     2221 gaagtgctgc agctttaagg aatctcatgg caaataggcc tgcgaagtac aaggatgcca
     2281 atattatgtc tcctggctca agcttgccat ctcttcatgt taggaaacaa aaagccctag
     2341 aagcagaatt agatgctcag cacttatcag aaacttttga caatatagac aatttaagtc
     2401 ccaaggcatc tcatcgtagt aagcagagac acaagcaaag tctctatggt gattatgttt
     2461 ttgacaccaa tcgacatgat gataataggt cagacaattt taatactggc aacatgactg
     2521 tcctttcacc atatttgaat actacagtgt tacccagctc ctcttcatca agaggaagct
     2581 tagatagttc tcgttctgaa aaagatagaa gtttggagag agaacgcgga attggtctag
     2641 gcaactacca tccagcaaca gaaaatccag gaacttcttc aaagcgaggt ttgcagatct
     2701 ccaccactgc agcccagatt gccaaagtca tggaagaagt gtcagccatt catacctctc
     2761 aggaagacag aagttctggg tctaccactg aattacattg tgtgacagat gagagaaatg
     2821 cacttagaag aagctctgct gcccatacac attcaaacac ttacaatttc actaagtcgg
     2881 aaaattcaaa taggacatgt tctatgcctt atgccaaatt agaatacaag agatcttcaa
     2941 atgatagttt aaatagtgtc agtagtagtg atggttatgg taaaagaggt caaatgaaac
     3001 cctcgattga atcctattct gaagatgatg aaagtaagtt ttgcagttat ggtcaatacc
     3061 cagccgacct agcccataaa atacatagtg caaatcatat ggatgataat gatggagaac
     3121 tagatacacc aataaattat agtcttaaat attcagatga gcagttgaac tctggaaggc
     3181 aaagtccttc acagaatgaa agatgggcaa gacccaaaca cataatagaa gatgaaataa
     3241 aacaaagtga gcaaagacaa tcaaggaatc aaagtacaac ttatcctgtt tatactgaga
     3301 gcactgatga taaacacctc aagttccaac cacattttgg acagcaggaa tgtgtttctc
     3361 catacaggtc acggggagcc aatggttcag aaacaaatcg agtgggttct aatcatggaa
     3421 ttaatcaaaa tgtaagccag tctttgtgtc aagaagatga ctatgaagat gataagccta
     3481 ccaattatag tgaacgttac tctgaagaag aacagcatga agaagaagag agaccaacaa
     3541 attatagcat aaaatataat gaagagaaac gtcatgtgga tcagcctatt gattatagtt
     3601 taaaatatgc cacagatatt ccttcatcac agaaacagtc attttcattc tcaaagagtt
     3661 catctggaca aagcagtaaa accgaacata tgtcttcaag cagtgagaat acgtccacac
     3721 cttcatctaa tgccaagagg cagaatcagc tccatccaag ttctgcacag agtagaagtg
     3781 gtcagcctca aaaggctgcc acttgcaaag tttcttctat taaccaagaa acaatacaga
     3841 cttattgtgt agaagatact ccaatatgtt tttcaagatg tagttcatta tcatctttgt
     3901 catcagctga agatgaaata ggatgtaatc agacgacaca ggaagcagat tctgctaata
     3961 ccctgcaaat agcagaaata aaagaaaaga ttggaactag gtcagctgaa gatcctgtga
     4021 gcgaagttcc agcagtgtca cagcacccta gaaccaaatc cagcagactg cagggttcta
     4081 gtttatcttc agaatcagcc aggcacaaag ctgttgaatt ttcttcagga gcgaaatctc
     4141 cctccaaaag tggtgctcag acacccaaaa gtccacctga acactatgtt caggagaccc
     4201 cactcatgtt tagcagatgt acttctgtca gttcacttga tagttttgag agtcgttcga
     4261 ttgccagctc cgttcagagt gaaccatgca gtggaatggt aagtggcatt ataagcccca
     4321 gtgatcttcc agatagccct ggacaaacca tgccaccaag cagaagtaaa acacctccac
     4381 cacctcctca aacagctcaa accaagcgag aagtacctaa aaataaagca cctactgctg
     4441 aaaagagaga gagtggacct aagcaagctg cagtaaatgc tgcagttcag agggtccagg
     4501 ttcttccaga tgctgatact ttattacatt ttgccacgga aagtactcca gatggatttt
     4561 cttgttcatc cagcctgagt gctctgagcc tcgatgagcc atttatacag aaagatgtgg
     4621 aattaagaat aatgcctcca gttcaggaaa atgacaatgg gaatgaaaca gaatcagagc
     4681 agcctaaaga atcaaatgaa aaccaagaga aagaggcaga aaaaactatt gattctgaaa
     4741 aggacctatt agatgattca gatgatgatg atattgaaat actagaagaa tgtattattt
     4801 ctgccatgcc aacaaagtca tcacgtaaag caaaaaagcc agcccagact gcttcaaaat
     4861 tacctccacc tgtggcaagg aaaccaagtc agctgcctgt gtacaaactt ctaccatcac
     4921 aaaacaggtt gcaaccccaa aagcatgtta gttttacacc gggggatgat atgccacggg
     4981 tgtattgtgt tgaagggaca cctataaact tttccacagc tacatctcta agtgatctaa
     5041 caatcgaatc ccctccaaat gagttagctg ctggagaagg agttagagga ggggcacagt
     5101 caggtgaatt tgaaaaacga gataccattc ctacagaagg cagaagtaca gatgaggctc
     5161 aaggaggaaa aacctcatct gtaaccatac ctgaattgga tgacaataaa gcagaggaag
     5221 gtgatattct tgcagaatgc attaattctg ctatgcccaa agggaaaagt cacaagcctt
     5281 tccgtgtgaa aaagataatg gaccaggtcc agcaagcatc tgcgtcttct tctgcaccca
     5341 acaaaaatca gttagatggt aagaaaaaga aaccaacttc accagtaaaa cctataccac
     5401 aaaatactga atataggaca cgtgtaagaa aaaatgcaga ctcaaaaaat aatttaaatg
     5461 ctgagagagt tttctcagac aacaaagatt caaagaaaca gaatttgaaa aataattcca
     5521 aggtcttcaa tgataagctc ccaaataatg aagatagagt cagaggaagt tttgcttttg
     5581 attcacctca tcattacacg cctattgaag gaactcctta ctgtttttca cgaaatgatt
     5641 ctttgagttc tctagatttt gatgatgatg atgttgacct ttccagggaa aaggctgaat
     5701 taagaaaggc aaaagaaaat aaggaatcag aggctaaagt taccagccac acagaactaa
     5761 cctccaacca acaatcagct aataagacac aagctattgc aaagcagcca ataaatcgag
     5821 gtcagcctaa acccatactt cagaaacaat ccacttttcc ccagtcatcc aaagacatac
     5881 cagacagagg ggcagcaact gatgaaaagt tacagaattt tgctattgaa aatactccgg
     5941 tttgcttttc tcataattcc tctctgagtt ctctcagtga cattgaccaa gaaaacaaca
     6001 ataaagaaaa tgaacctatc aaagagactg agccccctga ctcacaggga gaaccaagta
     6061 aacctcaagc atcaggctat gctcctaaat catttcatgt tgaagatacc ccagtttgtt
     6121 tctcaagaaa cagttctctc agttctctta gtattgactc tgaagatgac ctgttgcagg
     6181 aatgtataag ctccgcaatg ccaaaaaaga aaaagccttc aagactcaag ggtgataatg
     6241 aaaaacatag tcccagaaat atgggtggca tattaggtga agatctgaca cttgatttga
     6301 aagatataca gagaccagat tcagaacatg gtctatcccc tgattcagaa aattttgatt
     6361 ggaaagctat tcaggaaggt gcaaattcca tagtaagtag tttacatcaa gctgctgctg
     6421 ctgcatgttt atctagacaa gcttcgtctg attcagattc catcctttcc ctgaaatcag
     6481 gaatctctct gggatcacca tttcatctta cacctgatca agaagaaaaa ccctttacaa
     6541 gtaataaagg cccacgaatt ctaaaaccag gggagaaaag tacattggaa actaaaaaga
     6601 tagaatctga aagtaaagga atcaaaggag gaaaaaaagt ttataaaagt ttgattactg
     6661 gaaaagttcg atctaattca gaaatttcag gccaaatgaa acagcccctt caagcaaaca
     6721 tgccttcaat ctctcgaggc aggacaatga ttcatattcc aggagttcga aatagctcct
     6781 caagtacaag tcctgtttct aaaaaaggcc caccccttaa gactccagcc tccaaaagcc
     6841 ctagtgaagg tcaaacagcc accacttctc ctagaggagc caagccatct gtgaaatcag
     6901 aattaagccc tgttgccagg cagacatccc aaataggtgg gtcaagtaaa gcaccttcta
     6961 gatcaggatc tagagattcg accccttcaa gacctgccca gcaaccatta agtagaccta
     7021 tacagtctcc tggccgaaac tcaatttccc ctggtagaaa tggaataagt cctcctaaca
     7081 aattatctca acttccaagg acatcatccc ctagtactgc ttcaactaag tcctcaggtt
     7141 ctggaaaaat gtcatataca tctccaggta gacagatgag ccaacagaac cttaccaaac
     7201 aaacaggttt atccaagaat gccagtagta ttccaagaag tgagtctgcc tccaaaggac
     7261 taaatcagat gaataatggt aatggagcca ataaaaaggt agaactttct agaatgtctt
     7321 caactaaatc aagtggaagt gaatctgata gatcagaaag acctgtatta gtacgccagt
     7381 caactttcat caaagaagct ccaagcccaa ccttaagaag aaaattggag gaatctgctt
     7441 catttgaatc tctttctcca tcatctagac cagcttctcc cactaggtcc caggcacaaa
     7501 ctccagtttt aagtccttcc cttcctgata tgtctctatc cacacattcg tctgttcagg
     7561 ctggtggatg gcgaaaactc ccacctaatc tcagtcccac tatagagtat aatgatggaa
     7621 gaccagcaaa gcgccatgat attgcacggt ctcattctga aagtccttct agacttccaa
     7681 tcaataggtc aggaacctgg aaacgtgagc acagcaaaca ttcatcatcc cttcctcgag
     7741 taagcacttg gagaagaact ggaagttcat cttcaattct ttctgcttca tcagaatcca
     7801 gtgaaaaagc aaaaagtgag gatgaaaaac atgtgaactc tatttcagga accaaacaaa
     7861 gtaaagaaaa ccaagtatcc gcaaaaggaa catggagaaa aataaaagaa aatgaatttt
     7921 ctcccacaaa tagtacttct cagaccgttt cctcaggtgc tacaaatggt gctgaatcaa
     7981 agactctaat ttatcaaatg gcacctgctg tttctaaaac agaggatgtt tgggtgagaa
     8041 ttgaggactg tcccattaac aatcctagat ctggaagatc tcccacaggt aatactcccc
     8101 cggtgattga cagtgtttca gaaaaggcaa atccaaacat taaagattca aaagataatc
     8161 aggcaaaaca aaatgtgggt aatggcagtg ttcccatgcg taccgtgggt ttggaaaatc
     8221 gcctgaactc ctttattcag gtggatgccc ctgaccaaaa aggaactgag ataaaaccag
     8281 gacaaaataa tcctgtccct gtatcagaga ctaatgaaag ttctatagtg gaacgtaccc
     8341 cattcagttc tagcagctca agcaaacaca gttcacctag tgggactgtt gctgccagag
     8401 tgactccttt taattacaac ccaagcccta ggaaaagcag cgcagatagc acttcagctc
     8461 ggccatctca gatcccaact ccagtgaata acaacacaaa gaagcgagat tccaaaactg
     8521 acagcacaga atccagtgga acccaaagtc ctaagcgcca ttctgggtct taccttgtga
     8581 catctgttta aaagagagga agaatgaaac taagaaaatt ctatgttaat tacaactgct
     8641 atatagacat tttgtttcaa atgaaacttt aaaagactga aaaattttgt aaataggttt
     8701 gattcttgtt agagggtttt tgttctggaa gccatatttg atagtatact ttgtcttcac
     8761 tggtcttatt ttgggaggca ctcttgatgg ttaggaaaaa aatagtaaag ccaagtatgt
     8821 ttgtacagta tgttttacat gtatttaaag tagcatccca tcccaacttc ctttaattat
     8881 tgcttgtctt aaaataatga acactacaga tagaaaatat gatatattgc tgttatcaat
     8941 catttctaga ttataaactg actaaactta catcagggaa aaattggtat ttatgcaaaa
     9001 aaaaatgttt ttgtccttgt gagtccatct aacatcataa ttaatcatgt ggctgtgaaa
     9061 ttcacagtaa tatggttccc gatgaacaag tttacccagc ctgctttgct ttactgcatg
     9121 aatgaaactg atggttcaat ttcagaagta atgattaaca gttatgtggt cacatgatgt
     9181 gcatagagat agctacagtg taataattta cactattttg tgctccaaac aaaacaaaaa
     9241 tctgtgtaac tgtaaaacat tgaatgaaac tattttacct gaactagatt ttatctgaaa
     9301 gtaggtagaa tttttgctat gctgtaattt gttgtatatt ctggtatttg aggtgagatg
     9361 gctgctcttt tattaatgag acatgaattg tgtctcaaca gaaactaaat gaacatttca
     9421 gaataaatta ttgctgtatg taaactgtta ctgaaattgg tatttgtttg aagggtcttg
     9481 tttcacattt gtattaataa ttgtttaaaa tgcctctttt aaaagcttat ataaattttt
     9541 ttcttcagct tctatgcatt aagagtaaaa ttcctcttac tgtaataaaa acaattgaag
     9601 aagactgttg ccacttaacc attccatgcg ttggcactta tctattcctg aaatttcttt
     9661 tatgtgatta gctcatcttg atttttaata tttttccact taaacttttt tttcttactc
     9721 cactggagct cagtaaaagt aaattcatgt aatagcaatg caagcagcct agcacagact
     9781 aagcattgag cataataggc ccacataatt tcctctttct taatattata gaattctgta
     9841 cttgaaattg attcttagac attgcagtct cttcgaggct ttacagtgta aactgtcttg
     9901 ccccttcatc ttcttgttgc aactgggtct gacatgaaca ctttttatca ccctgtatgt
     9961 tagggcaaga tctcagcagt gaagtataat cagcactttg ccatgctcag aaaattcaaa
    10021 tcacatggaa ctttagaggt agatttaata cgattaagat attcagaagt atattttaga
    10081 atccctgcct gttaaggaaa ctttatttgt ggtaggtaca gttctggggt acatgttaag
    10141 tgtcccctta tacagtggag ggaagtcttc cttcctgaag gaaaataaac tgacacttat
    10201 taactaagat aatttactta atatatcttc cctgatttgt tttaaaagat cagagggtga
    10261 ctgatgatac atgcatacat atttgttgaa taaatgaaaa tttattttta gtgataagat
    10321 tcatacactc tgtatttggg gagggaaaac ctttttaagc atggtggggc actcagatag
    10381 gagtgaatac acctacctgg tgccttgaaa atcacatcaa gtagttaatt atctacccct
    10441 tacctgtgtt tataacttcc aggtaatgag aatgattttt tttaaagcta aaatgccagt
    10501 aaataaaagt gctatgactt gagctaagat atttgactcc aatgcctgta ctgtgtctac
    10561 tgcaccactt tgtaaacact tcaatttact atctttgaaa tgattgacct ttaaattttt
    10621 gccaaatgtt atctgaaatt gtctatgaat accatctact tctgttgttt tcccaggctt
    10681 ccataaacaa tggagataca tgca
//
