LOCUS       NM_006218               9259 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens phosphatidylinositol-4,5-bisphosphate 3-kinase
            catalytic subunit alpha (PIK3CA), mRNA.
ACCESSION   NM_006218
VERSION     NM_006218.4
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 9259)
  AUTHORS   Wedemeyer,M.A., Ding,T., Garfinkle,E.A.R., Westfall,J.J.,
            Navarro,J.B., Hernandez Gonzalez,M.E., Varga,E.A., Witman,P.,
            Mardis,E.R., Cottrell,C.E., Miller,A.R. and Miller,K.E.
  TITLE     Defining the transcriptome of PIK3CA-altered cells in a human
            capillary malformation using single cell long-read sequencing
  JOURNAL   Sci Rep 14 (1), 25440 (2024)
   PUBMED   39455600
  REMARK    GeneRIF: Defining the transcriptome of PIK3CA-altered cells in a
            human capillary malformation using single cell long-read
            sequencing.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 9259)
  AUTHORS   Herms,A., Colom,B., Piedrafita,G., Kalogeropoulou,A., Banerjee,U.,
            King,C., Abby,E., Murai,K., Caseda,I., Fernandez-Antoran,D.,
            Ong,S.H., Hall,M.W.J., Bryant,C., Sood,R.K., Fowler,J.C., Pol,A.,
            Frezza,C., Vanhaesebroeck,B. and Jones,P.H.
  TITLE     Organismal metabolism regulates the expansion of oncogenic PIK3CA
            mutant clones in normal esophagus
  JOURNAL   Nat Genet 56 (10), 2144-2157 (2024)
   PUBMED   39169259
  REMARK    GeneRIF: Organismal metabolism regulates the expansion of oncogenic
            PIK3CA mutant clones in normal esophagus.
REFERENCE   3  (bases 1 to 9259)
  AUTHORS   Vida-Navas,E., Barca-Tierno,V., Lopez-Gomez,V., Salazar,M.T.,
            Moreno-Pelayo,M.A. and Guillen-Ponce,C.
  TITLE     Constitutional Mutation of PIK3CA: A Variant of Cowden Syndrome?
  JOURNAL   Genes (Basel) 15 (9), 1209 (2024)
   PUBMED   39336800
  REMARK    GeneRIF: Constitutional Mutation of PIK3CA: A Variant of Cowden
            Syndrome?
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 9259)
  AUTHORS   Voutsadakis,I.A.
  TITLE     PIK3CA Mutated Colorectal Cancers Without KRAS, NRAS and BRAF
            Mutations Possess Common and Potentially Targetable Mutations in
            Epigenetic Modifiers and DNA Damage Response Genes
  JOURNAL   Cancer Genomics Proteomics 21 (5), 533-548 (2024)
   PUBMED   39191495
  REMARK    GeneRIF: PIK3CA Mutated Colorectal Cancers Without KRAS, NRAS and
            BRAF Mutations Possess Common and Potentially Targetable Mutations
            in Epigenetic Modifiers and DNA Damage Response Genes.
REFERENCE   5  (bases 1 to 9259)
  AUTHORS   Chen,H., Sun,B., Liu,H., Gao,W., Qiu,Y., Hua,C. and Lin,X.
  TITLE     Delineation of the phenotypes and genotypes of PIK3CA-related
            overgrowth spectrum in East asians
  JOURNAL   Mol Genet Genomics 299 (1), 66 (2024)
   PUBMED   38980418
  REMARK    GeneRIF: Delineation of the phenotypes and genotypes of
            PIK3CA-related overgrowth spectrum in East asians.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 9259)
  AUTHORS   Volinia,S., Hiles,I., Ormondroyd,E., Nizetic,D., Antonacci,R.,
            Rocchi,M. and Waterfield,M.D.
  TITLE     Molecular cloning, cDNA sequence, and chromosomal localization of
            the human phosphatidylinositol 3-kinase p110 alpha (PIK3CA) gene
  JOURNAL   Genomics 24 (3), 472-477 (1994)
   PUBMED   7713498
REFERENCE   7  (bases 1 to 9259)
  AUTHORS   Kodaki,T., Woscholski,R., Hallberg,B., Rodriguez-Viciana,P.,
            Downward,J. and Parker,P.J.
  TITLE     The activation of phosphatidylinositol 3-kinase by Ras
  JOURNAL   Curr Biol 4 (9), 798-806 (1994)
   PUBMED   7820549
REFERENCE   8  (bases 1 to 9259)
  AUTHORS   Mirzaa,G., Graham,J.M. Jr. and Keppler-Noreuil,K.
  TITLE     PIK3CA-Related Overgrowth Spectrum
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   23946963
REFERENCE   9  (bases 1 to 9259)
  AUTHORS   Hiles,I.D., Otsu,M., Volinia,S., Fry,M.J., Gout,I., Dhand,R.,
            Panayotou,G., Ruiz-Larrea,F., Thompson,A., Totty,N.F. et al.
  TITLE     Phosphatidylinositol 3-kinase: structure and expression of the 110
            kd catalytic subunit
  JOURNAL   Cell 70 (3), 419-429 (1992)
   PUBMED   1322797
REFERENCE   10 (bases 1 to 9259)
  AUTHORS   Carpenter,C.L., Duckworth,B.C., Auger,K.R., Cohen,B.,
            Schaffhausen,B.S. and Cantley,L.C.
  TITLE     Purification and characterization of phosphoinositide 3-kinase from
            rat liver
  JOURNAL   J Biol Chem 265 (32), 19704-19711 (1990)
   PUBMED   2174051
  REMARK    GeneRIF: This paper reports the first purification of a
            phosphoinositide 3-kinase and shows that the protein is a
            heterodimer of an 85 kd regulatory subunit that mediates binding to
            phosphorylated proteins and a 110 kd catalytic subunit.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC076966.25, BX484734.1,
            U79143.1, BX473473.1, AU129890.2, BQ228953.1, BX437219.2,
            AW445128.1 and AI379480.1.
            
            On Nov 23, 2018 this sequence version replaced NM_006218.3.
            
            Summary: Phosphatidylinositol 3-kinase is composed of an 85 kDa
            regulatory subunit and a 110 kDa catalytic subunit. The protein
            encoded by this gene represents the catalytic subunit, which uses
            ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene
            has been found to be oncogenic and has been implicated in cervical
            cancers. A pseudogene of this gene has been defined on chromosome
            22. [provided by RefSeq, Apr 2016].
            
            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 :: SRR1660805.126191.1,
                                           SRR1803615.87702.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000263967.4/ ENSP00000263967.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-166               AC076966.25        35734-35899
            167-471             BX484734.1         2-306
            472-544             U79143.1           149-221
            545-787             BX473473.1         143-385
            788-1201            U79143.1           465-878
            1202-1591           AU129890.2         118-507
            1592-2185           BQ228953.1         80-673
            2186-3103           U79143.1           1863-2780
            3104-3846           BX437219.2         11-753              c
            3847-3878           AW445128.1         13-44               c
            3879-8878           AC076966.25        122090-127089
            8879-9097           AI379480.1         174-392             c
            9098-9140           AC076966.25        127309-127351
            9141-9259           AI379480.1         12-130              c
FEATURES             Location/Qualifiers
     source          1..9259
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3q26.32"
     gene            1..9259
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /note="phosphatidylinositol-4,5-bisphosphate 3-kinase
                     catalytic subunit alpha"
                     /db_xref="GeneID:5290"
                     /db_xref="HGNC:HGNC:8975"
                     /db_xref="MIM:171834"
     exon            1..247
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            248..675
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     CDS             324..3530
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /EC_number="2.7.1.137"
                     /EC_number="2.7.11.1"
                     /EC_number="2.7.1.153"
                     /note="phosphatidylinositol 3-kinase, catalytic, alpha
                     polypeptide; phosphoinositide 3-kinase alpha;
                     phosphatidylinositol 3-kinase, catalytic, 110-KD, alpha;
                     phosphoinositide-3-kinase, catalytic, alpha polypeptide;
                     PI3-kinase p110 subunit alpha; ptdIns-3-kinase subunit
                     p110-alpha; phosphatidylinositol-4,5-bisphosphate 3-kinase
                     110 kDa catalytic subunit alpha; serine/threonine protein
                     kinase PIK3CA; mutant
                     phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic
                     subunit alpha"
                     /codon_start=1
                     /product="phosphatidylinositol 4,5-bisphosphate 3-kinase
                     catalytic subunit alpha isoform"
                     /protein_id="NP_006209.2"
                     /db_xref="CCDS:CCDS43171.1"
                     /db_xref="GeneID:5290"
                     /db_xref="HGNC:HGNC:8975"
                     /db_xref="MIM:171834"
                     /translation="MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLIT
                     IKHELFKEARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVI
                     EPVGNREEKILNREIGFAIGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPH
                     SRAMYVYPPNVESSPELPKHIYNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPE
                     QVIAEAIRKKTRSMLLSSEQLKLCVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSC
                     IMLGRMPNLMLMAKESLYSQLPMDCFTMPSYSRRISTATPYMNGETSTKSLWVINSAL
                     RIKILCATYVNVNIRDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLNYDIY
                     IPDLPRAARLCLSICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPH
                     GLEDLLNPIGVTGSNPNKETPCLELEFDWFSSVVKFPDMSVIEEHANWSVSREAGFSY
                     SHAGLSNRLARDNELRENDKEQLKAISTRDPLSEITEQEKDFLWSHRHYCVTIPEILP
                     KLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDCNYPDPMVRGFAVRCLEKYLT
                     DDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQ
                     RFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMR
                     RPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWLNWENPDIMSELLFQNNE
                     IIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHT
                     IMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIG
                     DRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECT
                     KTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIAYIRKTLALDK
                     TEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHALN"
     exon            676..885
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            886..1136
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1137..1382
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1383..1468
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1469..1574
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1575..1727
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1728..1862
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1863..1987
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1988..2069
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2070..2234
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2235..2338
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2339..2510
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2511..2617
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2618..2739
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2740..2818
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2819..2989
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2990..3107
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            3108..3259
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            3260..9259
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3980..3985
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /note="hexamer: ATTACA"
     polyA_site      4000
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /note="major polyA site"
     regulatory      4131..4136
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /note="hexamer: AATAAA"
     polyA_site      4152
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /note="major polyA site"
     regulatory      4466..4471
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /note="hexamer: ATTAAA"
     polyA_site      4491
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
     polyA_site      6659
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
     regulatory      7501..7506
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /note="hexamer: ATTAAA"
     polyA_site      7519
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
     regulatory      8542..8547
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /note="hexamer: AATATA"
     polyA_site      8563
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
     regulatory      9237..9242
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
                     /note="hexamer: ATTAAA"
     polyA_site      9259
                     /gene="PIK3CA"
                     /gene_synonym="CCM4; CLAPO; CLOVE; CWS5; HMH; MCAP; MCM;
                     MCMTC; p110-alpha; PI3K; PI3K-alpha"
ORIGIN      
        1 agttccggtg ccgccgctgc ggccgctgag gtgtcgggct gctgctgccg cggccgctgg
       61 gactggggct ggggccgccg gcgaggcagg gctcgggccc ggccgggcag ctccggagcg
      121 gcgggggaga ggggccggga ggcgggggcc gtgccgcccg ctctcctctc cctcggcgcc
      181 gccgccgccg cccgcggggc tgggacccga tgcggttaga gccgcggagc ctggaagagc
      241 cccgagcgtt tctgctttgg gacaaccata catctaattc cttaaagtag ttttatatgt
      301 aaaacttgca aagaatcaga acaatgcctc cacgaccatc atcaggtgaa ctgtggggca
      361 tccacttgat gcccccaaga atcctagtag aatgtttact accaaatgga atgatagtga
      421 ctttagaatg cctccgtgag gctacattaa taaccataaa gcatgaacta tttaaagaag
      481 caagaaaata ccccctccat caacttcttc aagatgaatc ttcttacatt ttcgtaagtg
      541 ttactcaaga agcagaaagg gaagaatttt ttgatgaaac aagacgactt tgtgaccttc
      601 ggctttttca acccttttta aaagtaattg aaccagtagg caaccgtgaa gaaaagatcc
      661 tcaatcgaga aattggtttt gctatcggca tgccagtgtg tgaatttgat atggttaaag
      721 atccagaagt acaggacttc cgaagaaata ttctgaacgt ttgtaaagaa gctgtggatc
      781 ttagggacct caattcacct catagtagag caatgtatgt ctatcctcca aatgtagaat
      841 cttcaccaga attgccaaag cacatatata ataaattaga taaagggcaa ataatagtgg
      901 tgatctgggt aatagtttct ccaaataatg acaagcagaa gtatactctg aaaatcaacc
      961 atgactgtgt accagaacaa gtaattgctg aagcaatcag gaaaaaaact cgaagtatgt
     1021 tgctatcctc tgaacaacta aaactctgtg ttttagaata tcagggcaag tatattttaa
     1081 aagtgtgtgg atgtgatgaa tacttcctag aaaaatatcc tctgagtcag tataagtata
     1141 taagaagctg tataatgctt gggaggatgc ccaatttgat gttgatggct aaagaaagcc
     1201 tttattctca actgccaatg gactgtttta caatgccatc ttattccaga cgcatttcca
     1261 cagctacacc atatatgaat ggagaaacat ctacaaaatc cctttgggtt ataaatagtg
     1321 cactcagaat aaaaattctt tgtgcaacct acgtgaatgt aaatattcga gacattgata
     1381 agatctatgt tcgaacaggt atctaccatg gaggagaacc cttatgtgac aatgtgaaca
     1441 ctcaaagagt accttgttcc aatcccaggt ggaatgaatg gctgaattat gatatataca
     1501 ttcctgatct tcctcgtgct gctcgacttt gcctttccat ttgctctgtt aaaggccgaa
     1561 agggtgctaa agaggaacac tgtccattgg catggggaaa tataaacttg tttgattaca
     1621 cagacactct agtatctgga aaaatggctt tgaatctttg gccagtacct catggattag
     1681 aagatttgct gaaccctatt ggtgttactg gatcaaatcc aaataaagaa actccatgct
     1741 tagagttgga gtttgactgg ttcagcagtg tggtaaagtt cccagatatg tcagtgattg
     1801 aagagcatgc caattggtct gtatcccgag aagcaggatt tagctattcc cacgcaggac
     1861 tgagtaacag actagctaga gacaatgaat taagggaaaa tgacaaagaa cagctcaaag
     1921 caatttctac acgagatcct ctctctgaaa tcactgagca ggagaaagat tttctatgga
     1981 gtcacagaca ctattgtgta actatccccg aaattctacc caaattgctt ctgtctgtta
     2041 aatggaattc tagagatgaa gtagcccaga tgtattgctt ggtaaaagat tggcctccaa
     2101 tcaaacctga acaggctatg gaacttctgg actgtaatta cccagatcct atggttcgag
     2161 gttttgctgt tcggtgcttg gaaaaatatt taacagatga caaactttct cagtatttaa
     2221 ttcagctagt acaggtccta aaatatgaac aatatttgga taacttgctt gtgagatttt
     2281 tactgaagaa agcattgact aatcaaagga ttgggcactt tttcttttgg catttaaaat
     2341 ctgagatgca caataaaaca gttagccaga ggtttggcct gcttttggag tcctattgtc
     2401 gtgcatgtgg gatgtatttg aagcacctga ataggcaagt cgaggcaatg gaaaagctca
     2461 ttaacttaac tgacattctc aaacaggaga agaaggatga aacacaaaag gtacagatga
     2521 agtttttagt tgagcaaatg aggcgaccag atttcatgga tgctctacag ggctttctgt
     2581 ctcctctaaa ccctgctcat caactaggaa acctcaggct tgaagagtgt cgaattatgt
     2641 cctctgcaaa aaggccactg tggttgaatt gggagaaccc agacatcatg tcagagttac
     2701 tgtttcagaa caatgagatc atctttaaaa atggggatga tttacggcaa gatatgctaa
     2761 cacttcaaat tattcgtatt atggaaaata tctggcaaaa tcaaggtctt gatcttcgaa
     2821 tgttacctta tggttgtctg tcaatcggtg actgtgtggg acttattgag gtggtgcgaa
     2881 attctcacac tattatgcaa attcagtgca aaggcggctt gaaaggtgca ctgcagttca
     2941 acagccacac actacatcag tggctcaaag acaagaacaa aggagaaata tatgatgcag
     3001 ccattgacct gtttacacgt tcatgtgctg gatactgtgt agctaccttc attttgggaa
     3061 ttggagatcg tcacaatagt aacatcatgg tgaaagacga tggacaactg tttcatatag
     3121 attttggaca ctttttggat cacaagaaga aaaaatttgg ttataaacga gaacgtgtgc
     3181 catttgtttt gacacaggat ttcttaatag tgattagtaa aggagcccaa gaatgcacaa
     3241 agacaagaga atttgagagg tttcaggaga tgtgttacaa ggcttatcta gctattcgac
     3301 agcatgccaa tctcttcata aatcttttct caatgatgct tggctctgga atgccagaac
     3361 tacaatcttt tgatgacatt gcatacattc gaaagaccct agccttagat aaaactgagc
     3421 aagaggcttt ggagtatttc atgaaacaaa tgaatgatgc acatcatggt ggctggacaa
     3481 caaaaatgga ttggatcttc cacacaatta aacagcatgc attgaactga aaagataact
     3541 gagaaaatga aagctcactc tggattccac actgcactgt taataactct cagcaggcaa
     3601 agaccgattg cataggaatt gcacaatcca tgaacagcat tagaatttac agcaagaaca
     3661 gaaataaaat actatataat ttaaataatg taaacgcaaa cagggtttga tagcacttaa
     3721 actagttcat ttcaaaatta agctttagaa taatgcgcaa tttcatgtta tgccttaagt
     3781 ccaaaaaggt aaactttgaa gattgtttgt atcttttttt aaaaaacaaa acaaaacaaa
     3841 aatccccaaa atatatagaa atgatggaga aggaaaaagt gatggttttt tttgtcttgc
     3901 aaatgttcta tgttttgaaa tgtggacaca acaaaggctg ttattgcatt aggtgtaagt
     3961 aaactggagt ttatgttaaa ttacattgat tggaaaagaa tgaaaatttc ttatttttcc
     4021 attgctgttc aatttatagt ttgaagtggg tttttgactg cttgtttaat gaagaaaaat
     4081 gcttggggtg gaagggactc ttgagatttc accagagact ttttcttttt aataaatcaa
     4141 accttttgat gatttgaggt tttatctgca gttttggaag cagtcacaaa tgagacctgt
     4201 tataaggtgg tatttttttt tttcttctgg acagtattta aaggatctta ttcttatttc
     4261 ccagggaaat tctgggctcc cacaaagtaa aaaaaaaaaa aaatcataga aaaagaatga
     4321 gcaggaatag ttcttattcc agaattgtac agtattcacc ttaagttgat tttttttctc
     4381 cttctgcaat tgaactgaat acatttttca tgcatgtttt ccagaaaata gaagtattaa
     4441 tgttattaaa aagattattt tttttattaa aggctattta tattatagaa actatcatta
     4501 atatatattc tttatttaca tgatctgtcc catagtcatg cattgttttg caccccaaat
     4561 tttttattgt tcatagcagc atggtcagct ttcttcttga tctatagatg aggctcaggc
     4621 actatcccat ttataccaat aaccagtgta taactactta aggaaaacat aaaaacttca
     4681 tcttctttcc ttttatttct tatgtgaatc tcccgtcttc cattctcttt tataattgag
     4741 aatgtctcaa tcatatgaaa ttagttacca gaattaacac aatttagact atcttcctga
     4801 ttccttaaac ccctttactg aagtatactc atgaataata ctttaaaata tgggggaata
     4861 gaaaccatga actttttacc tttttaaact atttatccat atctccaaag tagaacatta
     4921 aaccatttta agatatgtct cattcccaag tagtcagagc tcactctcca actttattaa
     4981 atactatttg agcacaggac acattcttaa acattttgaa aaacattaac ccaagatgta
     5041 gaggctactg ctagtcgtca ttctagaatc tgatatttta ctctgtattt gaaatgaatg
     5101 attaatgtcc taggaaatta gctttagcag atgtccaggt gccacatcaa aaaagtgcaa
     5161 taattattga cagtttttta gattaggcat attattggaa aacaacttta taaagagtga
     5221 acattgtata ctctagtaaa acagcatcac tttaaaaata ttcatttatg aaatctgtta
     5281 cctatagttg aagtcttgag tagtgaacaa gggactctaa taccaatact cttaatatct
     5341 ggctatttta gatcccttaa agggcataat tattggaaat ttaggtattt cactaaagca
     5401 tgtatataat attgccaaca agaaaagtaa atttgaagat taagggaact tacttctgca
     5461 aactgtcttg cgatagttaa gcagaattta aactctgttt taagcaggaa accagaaaga
     5521 ttattttgca gttgtagaag atttcataac ttattaaaac ttattaacat tttgtgttgt
     5581 ttagatatag gcagttgata catactaaca tcccagcctt ttcaatatca gggttaaatt
     5641 ataggaaaac tcagtaaaat ggtacaaatc tgaaagtttg atggtagaaa ctgaagattt
     5701 aacagagaac tgtgttttac ccgagtgcca aaaatgctgt gagcctcctt gcacaaaatt
     5761 tataccactt ttgcattttt atctatcagt ccagatagtt gtctcccctc cttctcccag
     5821 gacctctcca ccattaaaat gcacaaacca catggccgat ttcaccattt acatttattt
     5881 tcaaaagtta ctacaaccaa attaattcta ttagaagaaa tgtagacaaa ttctataaag
     5941 actatagatt gtgacctaag aaagaaatga ggcaaagaac caaacattga attaaatgct
     6001 acatgggtga ctaagatctg tttcaagtca gtgataatat agccacttct gggtacttca
     6061 gtatcagaga tcagttctcg tggtttagac agttcctatc tatagctgac tatccttgtc
     6121 cttgaatatg gtgtaactga ctattggctc tacagtttta ttgggccact taagaaatat
     6181 ttccttgaat aattattttg agaaaaagtc taaaagtaat aaaaataatt ttaaacacac
     6241 tgtagtaaga aatgactgtt ggaaaattat gctttcactt tctaccatat tctcagctat
     6301 acaaaaccat ttattttgaa gatttttaga ctactgttaa tttgaaatct gttactctta
     6361 ttgtggaatt tgttttttta aaaaagatgt ttctaattgg atttttaaaa gaagaatgga
     6421 atttggttgc tattttacaa tagaacctaa gctttttgtg gttcttagtg tcctatgtaa
     6481 aacttagtgt caaagtaatc aactttgaga ttttcccttc tattctgctt tatattaaaa
     6541 gcccattaga aaatgggaac ctggtgaata tataatgaat tgtaaaatat tttaatgtgt
     6601 aactttttca actgtgaaac tgacttgatt ttttgatgaa aacagctgct gataaagtat
     6661 tttgtgtaaa gtgtagttct tattaatcag gaaaatgatg acttgattag actgtatatg
     6721 ccctcttgga ttttatttta aatggattgg tgactttcac ataggtaaaa cacagtccat
     6781 ctgtattctt ttttccatca aaaatcgagt gatttggaat tataaaaaaa ttgtgagcag
     6841 cctatttgaa aggcatcatg gaaatttcac agcacaataa cacggatttg ttttttctta
     6901 atgatgtaaa tccgtttaat tcatactttg atcaatagcc catgcttgcc aactctgaag
     6961 aaatttaatt tccagcagta ttttaaagct agcctgttaa ctttttctga atatttaaag
     7021 ttcctctttt ttctatgtct gcacaaactg cagacctggg ctggacccac atactcaaga
     7081 gtccacctta agaaattatt ttgatgtcca agacatcact aaaatattta agtttaaaga
     7141 taatatgtgg tgttaataga ttgtggtgct tttactattt aaagacaact ttcatacttc
     7201 agatgttttt gagaagaggg gaatgtgagg ggagggggca gaacagggag gagttgtttg
     7261 aatgaattac attctttata tccatcctgc tcatttgggg catgtcttta agagaaggct
     7321 gaaagttgtg agagtatatt gtataccgta agagaatcaa ctcttcatca tggatgggat
     7381 tgtgaaggct gaactataaa attcagcatt gacagcatcc tcaattaata attcttggtg
     7441 acagaataat acagctgggc tgttttttaa aatataaaca ataccatttt taattattac
     7501 attaaaaatt gtaaatatat ctatgtgcca tggcctggga agcctgcttt cttttttcat
     7561 aaaaattatt tttactgtat gaaaagatca tggggtttag ctcaaaatat ctgtggtcct
     7621 gataaaattg gattggtaac tctacctcag aaggaaaatg ggaaaaaaaa atagatgagt
     7681 cacaattcaa tacttcaagc tcagaaactg tgcagatcac tgaattttag atttataaag
     7741 tcagagttgg catgccttgt ttttaatgat atggaagacc ttaagaaaaa aacttggctg
     7801 aagtttaatc gttggtccag ccatttgaaa aaggcaatag tttgaggagg ttcccgaatt
     7861 cggcatttga aattcatttt gttctctctt cttcattatt agtgcatttg gtgtgtgtat
     7921 acttgcacac aattctgttt gtgtacacac tgcttgctta gccctagtca agaggcatct
     7981 tttataaaag gtgtaaagaa atatcaaggt tctaaaattc ggaagagttt agaatttatt
     8041 aggagtttcc caagttggga tgttagtctt taaataaact tcatgcacct attccactta
     8101 aggttttgca cctccttttt attagtgcag tgccatttct tctgcttgat tttaggtatg
     8161 ttaatattcc agccttgcta gttagcataa agtgacaggt gtgagccatg aggaaatttt
     8221 ctgacttaat ttgtacacaa ctacatataa gagttttagt ggaggaaaaa aattagtccc
     8281 ttgtgcgtat acagtagtta ggtaaatgat ttttctacca acagtatact ccattcctca
     8341 tgtaggtaag tacagaaaag gtttttaaat gtattttttt agccagttaa agtctatgaa
     8401 tctatctgca accttattta atctgtcact ataataattt tgtggttatg ctaagaacca
     8461 tgtatacttt taggtattct tatttttgtc aatttttcta ggttggcaag gaggcagaaa
     8521 accttcattg tttcatatta aaatataatt agactaaact taattctagt atgaatttcc
     8581 aaaatcatta tctatttatt tcatttttat ttaattttgt ttttatttca tttttaaaag
     8641 tcccttgttc aatttaactt atgttcctaa gagaggttgg agaacttggc cttcatctga
     8701 tttcaaaaat gttttgagtt tcaaatgaag ttaatggttt cagtgtgatt cagtcctcag
     8761 acctaattgg gttgaataaa atctaaaaga atataccctt ttggagcata acattttaat
     8821 accttgggga atgtggcact accaaaagaa gactactaac acgtcagatg ttcacctgga
     8881 agctttatca agaaattcga accacccttt tggccccatt aattgtagca agtttatttc
     8941 tctatatttt gtcattcagt gaattgaagt cctgtggtat actgcattca ttagaagaaa
     9001 aacgttttta atgtcctttt aatgatggcc cagaaagcat ttgacacagc aagatgcatg
     9061 tgttactata ttgagaatat agaataataa cagtatcact aaatttaaga cctcttccca
     9121 gtcttgctgt tcctagcaag aagtttggcc tgtgactgca cttactgttt atgctcatca
     9181 gaaactgtca atgtctgctt ttctttaact ctgcagtctg taacatcacg ctgtttatta
     9241 aaaaaaaaaa gaaaaatta
//
