LOCUS       NM_000314               8515 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens phosphatase and tensin homolog (PTEN), transcript
            variant 1, mRNA.
ACCESSION   NM_000314
VERSION     NM_000314.8
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 8515)
  AUTHORS   Chowdhury,S.G., Misra,S., Ghosh,G., Mukherjee,A., Gopi,P.,
            Pandya,P., Islam,M.M. and Karmakar,P.
  TITLE     NHEJ is promoted by the phosphorylation and phosphatase activity of
            PTEN via regulation of DNA-PKcs
  JOURNAL   Biochim Biophys Acta Mol Cell Res 1871 (8), 119828 (2024)
   PUBMED   39197593
  REMARK    GeneRIF: NHEJ is promoted by the phosphorylation and phosphatase
            activity of PTEN via regulation of DNA-PKcs.
REFERENCE   2  (bases 1 to 8515)
  AUTHORS   Huang,X., Zhang,D., Zhang,D., Guo,J., Gu,G., Wang,Y., Wu,G.,
            Wang,C., Fu,B. and Li,K.
  TITLE     Decoding PTEN: from biological functions to signaling pathways in
            tumors
  JOURNAL   Mol Biol Rep 51 (1), 1089 (2024)
   PUBMED   39446204
  REMARK    GeneRIF: Decoding PTEN: from biological functions to signaling
            pathways in tumors.
            Review article
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 8515)
  AUTHORS   Derkyi-Kwarteng,L., Ghartey,F.N., Aidoo,E., Addae,E., Imbeah,E.G.,
            Brown,A.A. and Acquah,S.
  TITLE     A retrospective analysis suggests PTEN expression is associated
            with favorable clinicopathological features of breast cancer
  JOURNAL   Sci Rep 14 (1), 21645 (2024)
   PUBMED   39284903
  REMARK    GeneRIF: A retrospective analysis suggests PTEN expression is
            associated with favorable clinicopathological features of breast
            cancer.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 8515)
  AUTHORS   Trujano-Camacho,S., Cantu-de Leon,D., Perez-Yepez,E.,
            Contreras-Romero,C., Coronel-Hernandez,J., Millan-Catalan,O.,
            Rodriguez-Dorantes,M., Lopez-Camarillo,C., Gutierrez-Ruiz,C.,
            Jacobo-Herrera,N. and Perez-Plasencia,C.
  TITLE     HOTAIR Promotes the Hyperactivation of PI3K/Akt and
            Wnt/beta-Catenin Signaling Pathways via PTEN Hypermethylation in
            Cervical Cancer
  JOURNAL   Cells 13 (17), 1484 (2024)
   PUBMED   39273054
  REMARK    GeneRIF: HOTAIR Promotes the Hyperactivation of PI3K/Akt and
            Wnt/beta-Catenin Signaling Pathways via PTEN Hypermethylation in
            Cervical Cancer.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 8515)
  AUTHORS   Liang,H., He,S., Yang,J., Jia,X., Wang,P., Chen,X., Zhang,Z.,
            Zou,X., McNutt,M.A., Shen,W.H. and Yin,Y.
  TITLE     PTENalpha, a PTEN isoform translated through alternative
            initiation, regulates mitochondrial function and energy metabolism
  JOURNAL   Cell Metab 19 (5), 836-848 (2014)
   PUBMED   24768297
REFERENCE   6  (bases 1 to 8515)
  AUTHORS   Hopkins,B.D., Fine,B., Steinbach,N., Dendy,M., Rapp,Z., Shaw,J.,
            Pappas,K., Yu,J.S., Hodakoski,C., Mense,S., Klein,J., Pegno,S.,
            Sulis,M.L., Goldstein,H., Amendolara,B., Lei,L., Maurer,M.,
            Bruce,J., Canoll,P., Hibshoosh,H. and Parsons,R.
  TITLE     A secreted PTEN phosphatase that enters cells to alter signaling
            and survival
  JOURNAL   Science 341 (6144), 399-402 (2013)
   PUBMED   23744781
  REMARK    GeneRIF: identified a 576-amino acid translational variant of PTEN,
            PTEN-Long, that arises from an alternative translation start site
            519 base pairs upstream of the ATG initiation sequence; PTEN-Long
            is a membrane-permeable lipid phosphatase that is secreted from
            cells and can enter other cells
REFERENCE   7  (bases 1 to 8515)
  AUTHORS   Steck,P.A., Pershouse,M.A., Jasser,S.A., Yung,W.K., Lin,H.,
            Ligon,A.H., Langford,L.A., Baumgard,M.L., Hattier,T., Davis,T.,
            Frye,C., Hu,R., Swedlund,B., Teng,D.H. and Tavtigian,S.V.
  TITLE     Identification of a candidate tumour suppressor gene, MMAC1, at
            chromosome 10q23.3 that is mutated in multiple advanced cancers
  JOURNAL   Nat Genet 15 (4), 356-362 (1997)
   PUBMED   9090379
REFERENCE   8  (bases 1 to 8515)
  AUTHORS   Li,J., Yen,C., Liaw,D., Podsypanina,K., Bose,S., Wang,S.I., Puc,J.,
            Miliaresis,C., Rodgers,L., McCombie,R., Bigner,S.H.,
            Giovanella,B.C., Ittmann,M., Tycko,B., Hibshoosh,H., Wigler,M.H.
            and Parsons,R.
  TITLE     PTEN, a putative protein tyrosine phosphatase gene mutated in human
            brain, breast, and prostate cancer
  JOURNAL   Science 275 (5308), 1943-1947 (1997)
   PUBMED   9072974
REFERENCE   9  (bases 1 to 8515)
  AUTHORS   Peiffer,S.L., Herzog,T.J., Tribune,D.J., Mutch,D.G., Gersell,D.J.
            and Goodfellow,P.J.
  TITLE     Allelic loss of sequences from the long arm of chromosome 10 and
            replication errors in endometrial cancers
  JOURNAL   Cancer Res 55 (9), 1922-1926 (1995)
   PUBMED   7728760
REFERENCE   10 (bases 1 to 8515)
  AUTHORS   Yehia,L. and Eng,C.
  TITLE     PTEN Hamartoma Tumor Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301661
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC063965.8.
            
            On Aug 31, 2019 this sequence version replaced NM_000314.7.
            
            Summary: This gene was identified as a tumor suppressor that is
            mutated in a large number of cancers at high frequency. The protein
            encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate
            3-phosphatase. It contains a tensin like domain as well as a
            catalytic domain similar to that of the dual specificity protein
            tyrosine phosphatases. Unlike most of the protein tyrosine
            phosphatases, this protein preferentially dephosphorylates
            phosphoinositide substrates. It negatively regulates intracellular
            levels of phosphatidylinositol-3,4,5-trisphosphate in cells and
            functions as a tumor suppressor by negatively regulating AKT/PKB
            signaling pathway. The use of a non-canonical (CUG) upstream
            initiation site produces a longer isoform that initiates
            translation with a leucine, and is thought to be preferentially
            associated with the mitochondrial inner membrane. This longer
            isoform may help regulate energy metabolism in the mitochondria. A
            pseudogene of this gene is found on chromosome 9. Alternative
            splicing and the use of multiple translation start codons results
            in multiple transcript variants encoding different isoforms.
            [provided by RefSeq, Feb 2015].
            
            Transcript Variant: This variant (1) encodes multiple isoforms due
            to the use of alternative translation initiation codons. The
            longest isoform (PTEN-L, PMID:23744781; also known as PTENalpha,
            PMID: 24768297) is derived from the use of an upstream non-AUG
            (CUG) start codon, while two shorter isoforms are derived from
            downstream AUG start codons. The most abundant isoform (PTEN),
            which is derived from the use of the 5'-most AUG start codon, is
            represented in this RefSeq.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: U92436.1, BC005821.2 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            CDS uses downstream in-frame AUG :: experimental evidence
                                                (PMID:24768297)
            MANE Ensembl match               :: ENST00000371953.8/
                                                ENSP00000361021.3
            RefSeq Select criteria           :: based on expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-924               AC063965.8         184209-185132       c
            925-1009            AC063965.8         154648-154732       c
            1010-1054           AC063965.8         123200-123244       c
            1055-1098           AC063965.8         117668-117711       c
            1099-1337           AC063965.8         115506-115744       c
            1338-1479           AC063965.8         96498-96639         c
            1480-1646           AC063965.8         90738-90904         c
            1647-1871           AC063965.8         87639-87863         c
            1872-8515           AC063965.8         76827-83470         c
FEATURES             Location/Qualifiers
     source          1..8515
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10q23.31"
     gene            1..8515
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /note="phosphatase and tensin homolog"
                     /db_xref="GeneID:5728"
                     /db_xref="HGNC:HGNC:9588"
                     /db_xref="MIM:601728"
     exon            1..924
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /inference="alignment:Splign:2.1.0"
     CDS             846..2057
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /EC_number="3.1.3.67"
                     /EC_number="3.1.3.16"
                     /EC_number="3.1.3.48"
                     /note="isoform PTEN is encoded by transcript variant 1;
                     phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and
                     dual-specificity protein phosphatase PTEN; mitochondrial
                     PTENalpha; MMAC1 phosphatase and tensin homolog deleted on
                     chromosome 10; mutated in multiple advanced cancers 1;
                     phosphatase and tensin-like protein; PTENepsilon; PTEN
                     variant PTEN-K267Rfs*9; PTEN variant PTEN-R234Afs*11;
                     inositol polyphosphate 3-phosphatase; mitochondrial
                     phosphatase and tensin protein alpha; protein tyrosine
                     phosphatase; PTEN variant PTEN-L247*"
                     /codon_start=1
                     /product="phosphatidylinositol 3,4,5-trisphosphate
                     3-phosphatase and dual-specificity protein phosphatase
                     PTEN isoform PTEN"
                     /protein_id="NP_000305.3"
                     /db_xref="CCDS:CCDS31238.1"
                     /db_xref="GeneID:5728"
                     /db_xref="HGNC:HGNC:9588"
                     /db_xref="MIM:601728"
                     /translation="MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEG
                     VYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIK
                     PFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRT
                     RDKKGVTIPSQRRYVYYYSYLLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVC
                     QLKVKIYSSNSGPTRREDKFMYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVN
                     TFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKANKDKAN
                     RYFSPNFKVKLYFTKTVEEPSNPEASSSTSVTPDVSDNEPDHYRYSDTTDSDPENEPF
                     DEDQHTQITKV"
     exon            925..1009
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1010..1054
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1055..1098
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1099..1337
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1338..1479
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1480..1646
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1647..1871
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1872..8515
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2093..2098
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /note="hexamer: AATAAA"
     polyA_site      2115
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /note="major polyA site"
     regulatory      2937..2942
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /note="hexamer: ATTAAA"
     polyA_site      2961
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
     regulatory      5319..5324
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /note="hexamer: TATAAA"
     polyA_site      5340
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
     regulatory      8107..8112
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /note="hexamer: ATTAAA"
     polyA_site      8129
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
     regulatory      8382..8387
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /note="hexamer: ATTAAA"
     polyA_site      8407
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
     regulatory      8490..8495
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
                     /note="hexamer: ATTAAA"
     polyA_site      8515
                     /gene="PTEN"
                     /gene_synonym="10q23del; BZS; CWS1; DEC; GLM2; MHAM;
                     MMAC1; PTEN1; PTENbeta; PTENgama; TEP1"
ORIGIN      
        1 gttctctcct ctcggaagct gcagccatga tggaagtttg agagttgagc cgctgtgagg
       61 cgaggccggg ctcaggcgag ggagatgaga gacggcggcg gccgcggccc ggagcccctc
      121 tcagcgcctg tgagcagccg cgggggcagc gccctcgggg agccggccgg cctgcggcgg
      181 cggcagcggc ggcgtttctc gcctcctctt cgtcttttct aaccgtgcag cctcttcctc
      241 ggcttctcct gaaagggaag gtggaagccg tgggctcggg cgggagccgg ctgaggcgcg
      301 gcggcggcgg cggcacctcc cgctcctgga gcggggggga gaagcggcgg cggcggcggc
      361 cgcggcggct gcagctccag ggagggggtc tgagtcgcct gtcaccattt ccagggctgg
      421 gaacgccgga gagttggtct ctccccttct actgcctcca acacggcggc ggcggcggct
      481 ggcacatcca gggacccggg ccggttttaa acctcccgtg cgccgccgcc gcaccccccg
      541 tggcccgggc tccggaggcc gccggcggag gcagccgttc ggaggattat tcgtcttctc
      601 cccattccgc tgccgccgct gccaggcctc tggctgctga ggagaagcag gcccagtcgc
      661 tgcaaccatc cagcagccgc cgcagcagcc attacccggc tgcggtccag agccaagcgg
      721 cggcagagcg aggggcatca gctaccgcca agtccagagc catttccatc ctgcagaaga
      781 agccccgcca ccagcagctt ctgccatctc tctcctcctt tttcttcagc cacaggctcc
      841 cagacatgac agccatcatc aaagagatcg ttagcagaaa caaaaggaga tatcaagagg
      901 atggattcga cttagacttg acctatattt atccaaacat tattgctatg ggatttcctg
      961 cagaaagact tgaaggcgta tacaggaaca atattgatga tgtagtaagg tttttggatt
     1021 caaagcataa aaaccattac aagatataca atctttgtgc tgaaagacat tatgacaccg
     1081 ccaaatttaa ttgcagagtt gcacaatatc cttttgaaga ccataaccca ccacagctag
     1141 aacttatcaa acccttttgt gaagatcttg accaatggct aagtgaagat gacaatcatg
     1201 ttgcagcaat tcactgtaaa gctggaaagg gacgaactgg tgtaatgata tgtgcatatt
     1261 tattacatcg gggcaaattt ttaaaggcac aagaggccct agatttctat ggggaagtaa
     1321 ggaccagaga caaaaaggga gtaactattc ccagtcagag gcgctatgtg tattattata
     1381 gctacctgtt aaagaatcat ctggattata gaccagtggc actgttgttt cacaagatga
     1441 tgtttgaaac tattccaatg ttcagtggcg gaacttgcaa tcctcagttt gtggtctgcc
     1501 agctaaaggt gaagatatat tcctccaatt caggacccac acgacgggaa gacaagttca
     1561 tgtactttga gttccctcag ccgttacctg tgtgtggtga tatcaaagta gagttcttcc
     1621 acaaacagaa caagatgcta aaaaaggaca aaatgtttca cttttgggta aatacattct
     1681 tcataccagg accagaggaa acctcagaaa aagtagaaaa tggaagtcta tgtgatcaag
     1741 aaatcgatag catttgcagt atagagcgtg cagataatga caaggaatat ctagtactta
     1801 ctttaacaaa aaatgatctt gacaaagcaa ataaagacaa agccaaccga tacttttctc
     1861 caaattttaa ggtgaagctg tacttcacaa aaacagtaga ggagccgtca aatccagagg
     1921 ctagcagttc aacttctgta acaccagatg ttagtgacaa tgaacctgat cattatagat
     1981 attctgacac cactgactct gatccagaga atgaaccttt tgatgaagat cagcatacac
     2041 aaattacaaa agtctgaatt tttttttatc aagagggata aaacaccatg aaaataaact
     2101 tgaataaact gaaaatggac cttttttttt ttaatggcaa taggacattg tgtcagatta
     2161 ccagttatag gaacaattct cttttcctga ccaatcttgt tttaccctat acatccacag
     2221 ggttttgaca cttgttgtcc agttgaaaaa aggttgtgta gctgtgtcat gtatatacct
     2281 ttttgtgtca aaaggacatt taaaattcaa ttaggattaa taaagatggc actttcccgt
     2341 tttattccag ttttataaaa agtggagaca gactgatgtg tatacgtagg aattttttcc
     2401 ttttgtgttc tgtcaccaac tgaagtggct aaagagcttt gtgatatact ggttcacatc
     2461 ctaccccttt gcacttgtgg caacagataa gtttgcagtt ggctaagaga ggtttccgaa
     2521 gggttttgct acattctaat gcatgtattc gggttagggg aatggaggga atgctcagaa
     2581 aggaaataat tttatgctgg actctggacc atataccatc tccagctatt tacacacacc
     2641 tttctttagc atgctacagt tattaatctg gacattcgag gaattggccg ctgtcactgc
     2701 ttgttgtttg cgcatttttt tttaaagcat attggtgcta gaaaaggcag ctaaaggaag
     2761 tgaatctgta ttggggtaca ggaatgaacc ttctgcaaca tcttaagatc cacaaatgaa
     2821 gggatataaa aataatgtca taggtaagaa acacagcaac aatgacttaa ccatataaat
     2881 gtggaggcta tcaacaaaga atgggcttga aacattataa aaattgacaa tgatttatta
     2941 aatatgtttt ctcaattgta acgacttctc catctcctgt gtaatcaagg ccagtgctaa
     3001 aattcagatg ctgttagtac ctacatcagt caacaactta cacttatttt actagttttc
     3061 aatcataata cctgctgtgg atgcttcatg tgctgcctgc aagcttcttt tttctcatta
     3121 aatataaaat attttgtaat gctgcacaga aattttcaat ttgagattct acagtaagcg
     3181 ttttttttct ttgaagattt atgatgcact tattcaatag ctgtcagccg ttccaccctt
     3241 ttgaccttac acattctatt acaatgaatt ttgcagtttt gcacattttt taaatgtcat
     3301 taactgttag ggaattttac ttgaatactg aatacatata atgtttatat taaaaaggac
     3361 atttgtgtta aaaaggaaat tagagttgca gtaaactttc aatgctgcac acaaaaaaaa
     3421 gacatttgat ttttcagtag aaattgtcct acatgtgctt tattgatttg ctattgaaag
     3481 aatagggttt tttttttttt tttttttttt ttttttaaat gtgcagtgtt gaatcatttc
     3541 ttcatagtgc tcccccgagt tgggactagg gcttcaattt cacttcttaa aaaaaatcat
     3601 catatatttg atatgcccag actgcatacg attttaagcg gagtacaact actattgtaa
     3661 agctaatgtg aagatattat taaaaaggtt tttttttcca gaaatttggt gtcttcaaat
     3721 tataccttca ccttgacatt tgaatatcca gccattttgt ttcttaatgg tataaaattc
     3781 cattttcaat aacttattgg tgctgaaatt gttcactagc tgtggtctga cctagttaat
     3841 ttacaaatac agattgaata ggacctacta gagcagcatt tatagagttt gatggcaaat
     3901 agattaggca gaacttcatc taaaatattc ttagtaaata atgttgacac gttttccata
     3961 ccttgtcagt ttcattcaac aatttttaaa tttttaacaa agctcttagg atttacacat
     4021 ttatatttaa acattgatat atagagtatt gattgattgc tcataagtta aattggtaaa
     4081 gttagagaca actattctaa cacctcacca ttgaaattta tatgccacct tgtctttcat
     4141 aaaagctgaa aattgttacc taaaatgaaa atcaacttca tgttttgaag atagttataa
     4201 atattgttct ttgttacaat ttcgggcacc gcatattaaa acgtaacttt attgttccaa
     4261 tatgtaacat ggagggccag gtcataaata atgacattat aatgggcttt tgcactgtta
     4321 ttatttttcc tttggaatgt gaaggtctga atgagggttt tgattttgaa tgtttcaatg
     4381 tttttgagaa gccttgctta cattttatgg tgtagtcatt ggaaatggaa aaatggcatt
     4441 atatatatta tatatataaa tatatattat acatactctc cttactttat ttcagttacc
     4501 atccccatag aatttgacaa gaattgctat gactgaaagg ttttcgagtc ctaattaaaa
     4561 ctttatttat ggcagtattc ataattagcc tgaaatgcat tctgtaggta atctctgagt
     4621 ttctggaata ttttcttaga ctttttggat gtgcagcagc ttacatgtct gaagttactt
     4681 gaaggcatca cttttaagaa agcttacagt tgggccctgt accatcccaa gtcctttgta
     4741 gctcctcttg aacatgtttg ccatactttt aaaagggtag ttgaataaat agcatcacca
     4801 ttctttgctg tggcacaggt tataaactta agtggagttt accggcagca tcaaatgttt
     4861 cagctttaaa aaataaaagt agggtacaag tttaatgttt agttctagaa attttgtgca
     4921 atatgttcat aacgatggct gtggttgcca caaagtgcct cgtttacctt taaatactgt
     4981 taatgtgtca tgcatgcaga tggaaggggt ggaactgtgc actaaagtgg gggctttaac
     5041 tgtagtattt ggcagagttg ccttctacct gccagttcaa aagttcaacc tgttttcata
     5101 tagaatatat atactaaaaa atttcagtct gttaaacagc cttactctga ttcagcctct
     5161 tcagatactc ttgtgctgtg cagcagtggc tctgtgtgta aatgctatgc actgaggata
     5221 cacaaaaata ccaatatgat gtgtacagga taatgcctca tcccaatcag atgtccattt
     5281 gttattgtgt ttgttaacaa ccctttatct cttagtgtta taaactccac ttaaaactga
     5341 ttaaagtctc attcttgtca ttgtgtgggt gttttattaa atgagagttt ataattcaaa
     5401 ttgcttaagt ccattgaagt tttaattaat gggcagccaa atgtgaatac aaagttttca
     5461 gttttttttt ttcctgctgt ccttcaaagc ctactgttta aaaaaaaaaa aaaaaaaaaa
     5521 catggcctga gagtagagta tctgtctact catgtttaat taaggaaaaa cacttatttt
     5581 tagggcttta gtcatcactt cataaattgt ataagcacat taaatagcgt tctagtcctg
     5641 aaaaagtcca agattcttag aaaattgtgc atatttttat tatgacagat gtttgaagat
     5701 aattccccag aatggatttg atactttaga tttcaatttt gtggcttttg tctattattc
     5761 tgtactctgc catcagcata tggaaagctt catttactca tcatgacttg tgccatataa
     5821 aaattgatat ttcggaatag tctaaaggac tttttgtact tgaatttaat catgttgttt
     5881 ctaatattct taaaagcttg aagactaaag catatccttt caacaaagca tagtaaggta
     5941 ataagaaagt gtagtttgta caagtgttaa aaaaataaag tagacaatgt tacagtggga
     6001 cttattattt caagtttaca ttttctccat gtaatttttt aaaaagtaaa tgaaaaaatg
     6061 tgcaataatg taaaatatga agtgtatgtg tacacacatt ttatttttcg gtatcttggg
     6121 tatacgtatg gttgaaaact atactggagt ctaaaagtat tctaatttat aagaagacat
     6181 tttggtgatg tttgaaaaat agaaatgtgc tagttttgtt tttatatcat gtcctttgta
     6241 cgttgtaata tgagctggct tggttcagta aatgccatca ccatttccat tgagaattta
     6301 aaactcacca gtgtttaata tgcaggcttc caaaggctta tgaaaaaaat caagaccctt
     6361 aaatctagtt aatttgctgc taacatgaaa ctctttggtt cttttatttt tgccagataa
     6421 ttagacacac atctaaagct tagtcttaaa tggcttaagt gtagctattg attagtgctg
     6481 ttgctagttc agaaagaaat gtttgtgaat ggaaacaaga atattcagtc caaactgttg
     6541 taaggacagt acctgaaaac caggaaacag gataatggaa aaagtctttt aaagatgaaa
     6601 tgttggagcc aactttctta tagaattaat tgtatgtggc tatagaaagc ctaatgattg
     6661 ttgcttattt ttgagagcat attattcttt tatgaccata atcttgctgt ttttccatct
     6721 tccaaaagat cttccttcta atatgtatat cagaatgtgg gtagccagtc agacaaattc
     6781 atattggttg gtagctttaa aaagtttgta atgtgaagac aggaaaggac aaaatagttt
     6841 gctttggtgg tagtactctg gttgttaagc taggtatttt gagactactt ccccatcaca
     6901 acaacaataa aataatcact cataatccta tcacctggag acatagccat cgttaatatg
     6961 ttagtgacta tacaatcatg ttttcttctg tatatccatg tatattcttt aaaaatgaaa
     7021 tttatactgt acctgatctc aaagcttttt agcttagtat atctgtcatg aatttgtagg
     7081 atgttccatt gcatcagaaa acggacagtg atttgattac tttctaatgc cacagatgca
     7141 gattacatgt agttattgag aatcctttcg aattcagtgg cttaatcatg aatgtctaaa
     7201 tattgttgac attaggatga tacatgtaaa ttaaagttac atttgtttag catagacaag
     7261 cttaacattg tagatgtttc tcttcaaaaa tcatcttaaa catttgcatt tggaattgtg
     7321 ttaaatagaa tgtgtgaaac actgtattag taaacttcat cacctttcta cttccttata
     7381 gtttgaactt ttcagttttt gtagttccca aacagttgct caatttagag caaattaatt
     7441 taacacctgc caaaaaaagg ctgctgttgg cttatcagtt gtctttaaat tcaaatgctc
     7501 atgtgacttt tatcacatca aaaaatattt cattaatgat tcacctttag ctctgaaaat
     7561 taccgcgttt agtaattata gtgggcttat aaaaacatgc aactcttttt gatagttatt
     7621 tgagaatttt ggtgaaaaat atttagctga gggcagtata gaacttataa accaatatat
     7681 tgatattttt aaaacatttt tacatataag taaactgcca tctttgagca taactacatt
     7741 taaaaataaa gctgcatatt tttaaatcaa gtgtttaaca agaatttata ttttttattt
     7801 tttaaaatta aaaataattt atatttcctc tgttgcatga ggattctcat ctgtgcttat
     7861 aatggttaga gattttattt gtgtggaatg aagtgaggct tgtagtcatg gttctagtgt
     7921 ttcagtttgc caagtctgtt tactgcagtg aaattcatca aatgtttcag tgtggttttc
     7981 tgtagcctat catttactgg ctattttttt atgtacacct ttaggatttt ctgcctactc
     8041 tatccagttg tccaaatgat atcctacatt ttacaaatgc cctttcagtt tctattttct
     8101 ttttccatta aattgccctc atgtcctaat gtgcagtttg taagtgtgtg tgtgtgtgtc
     8161 tgtgtgtgtg tgaatttgat tttcaagagt gctagacttc caatttgaga gattaaataa
     8221 tttaattcag gcaaacattt ttcattggaa tttcacagtt cattgtaatg aaaatgttaa
     8281 tcctggatga cctttgacat acagtaatga atcttggata ttaatgaatt tgttagtagc
     8341 atcttgatgt gtgttttaat gagttatttt caaagttgtg cattaaacca aagttggcat
     8401 actggaagtg tttatatcaa gttccatttg gctactgatg gacaaaaaat agaaatgcct
     8461 tcctatggag agtatttttc ctttaaaaaa ttaaaaaggt taattatttt gacta
//
