LOCUS       NM_002645               8428 bp    mRNA    linear   PRI 12-FEB-2025
DEFINITION  Homo sapiens phosphatidylinositol-4-phosphate 3-kinase catalytic
            subunit type 2 alpha (PIK3C2A), transcript variant 1, mRNA.
ACCESSION   NM_002645 XM_005252977
VERSION     NM_002645.4
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 8428)
  AUTHORS   Soliman,S.E., Abouelenin,M.A.H., Samy,N.I., Omar,M.M. and
            Alrefai,A.A.
  TITLE     Various Expressions of PIK3C2A and TXNIP Genes and Their Potential
            Role as Independent Risk Factors for Chronic Stable Angina and
            Acute Coronary Syndrome
  JOURNAL   Biomolecules 13 (2), 302 (2023)
   PUBMED   36830671
  REMARK    GeneRIF: Various Expressions of PIK3C2A and TXNIP Genes and Their
            Potential Role as Independent Risk Factors for Chronic Stable
            Angina and Acute Coronary Syndrome.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 8428)
  AUTHORS   Gulluni,F., Prever,L., Li,H., Krafcikova,P., Corrado,I., Lo,W.T.,
            Margaria,J.P., Chen,A., De Santis,M.C., Cnudde,S.J., Fogerty,J.,
            Yuan,A., Massarotti,A., Sarijalo,N.T., Vadas,O., Williams,R.L.,
            Thelen,M., Powell,D.R., Schueler,M., Wiesener,M.S., Balla,T.,
            Baris,H.N., Tiosano,D., McDermott,B.M. Jr., Perkins,B.D., Ghigo,A.,
            Martini,M., Haucke,V., Boura,E., Merlo,G.R., Buchner,D.A. and
            Hirsch,E.
  TITLE     PI(3,4)P2-mediated cytokinetic abscission prevents early senescence
            and cataract formation
  JOURNAL   Science 374 (6573), eabk0410 (2021)
   PUBMED   34882480
  REMARK    GeneRIF: PI(3,4)P2-mediated cytokinetic abscission prevents early
            senescence and cataract formation.
REFERENCE   3  (bases 1 to 8428)
  AUTHORS   Koch,P.A., Dornan,G.L., Hessenberger,M. and Haucke,V.
  TITLE     The molecular mechanisms mediating class II PI 3-kinase function in
            cell physiology
  JOURNAL   FEBS J 288 (24), 7025-7042 (2021)
   PUBMED   33387369
  REMARK    GeneRIF: The molecular mechanisms mediating class II PI 3-kinase
            function in cell physiology.
            Review article
REFERENCE   4  (bases 1 to 8428)
  AUTHORS   Shimizu,S., Yoshioka,K., Aki,S. and Takuwa,Y.
  TITLE     Class II phosphatidylinositol 3-kinase-C2alpha is essential for
            Notch signaling by regulating the endocytosis of gamma-secretase in
            endothelial cells
  JOURNAL   Sci Rep 11 (1), 5199 (2021)
   PUBMED   33664344
  REMARK    GeneRIF: Class II phosphatidylinositol 3-kinase-C2alpha is
            essential for Notch signaling by regulating the endocytosis of
            gamma-secretase in endothelial cells.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 8428)
  AUTHORS   Aki,S., Yoshioka,K., Takuwa,N. and Takuwa,Y.
  TITLE     TGFbeta receptor endocytosis and Smad signaling require
            synaptojanin1, PI3K-C2alpha-, and INPP4B-mediated phosphoinositide
            conversions
  JOURNAL   Mol Biol Cell 31 (5), 360-372 (2020)
   PUBMED   31913757
  REMARK    GeneRIF: TGFbeta receptor endocytosis and Smad signaling require
            synaptojanin1, PI3K-C2alpha-, and INPP4B-mediated phosphoinositide
            conversions.
REFERENCE   6  (bases 1 to 8428)
  AUTHORS   Zhang,J., Banfic,H., Straforini,F., Tosi,L., Volinia,S. and
            Rittenhouse,S.E.
  TITLE     A type II phosphoinositide 3-kinase is stimulated via activated
            integrin in platelets. A source of phosphatidylinositol 3-phosphate
  JOURNAL   J Biol Chem 273 (23), 14081-14084 (1998)
   PUBMED   9603905
REFERENCE   7  (bases 1 to 8428)
  AUTHORS   Borgatti,P., Zauli,G., Cantley,L.C. and Capitani,S.
  TITLE     Extracellular HIV-1 Tat protein induces a rapid and selective
            activation of protein kinase C (PKC)-alpha, and -epsilon and -zeta
            isoforms in PC12 cells
  JOURNAL   Biochem Biophys Res Commun 242 (2), 332-337 (1998)
   PUBMED   9446795
REFERENCE   8  (bases 1 to 8428)
  AUTHORS   Borgatti,P., Zauli,G., Colamussi,M.L., Gibellini,D., Previati,M.,
            Cantley,L.L. and Capitani,S.
  TITLE     Extracellular HIV-1 Tat protein activates phosphatidylinositol 3-
            and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells
  JOURNAL   Eur J Immunol 27 (11), 2805-2811 (1997)
   PUBMED   9394803
REFERENCE   9  (bases 1 to 8428)
  AUTHORS   Domin,J., Pages,F., Volinia,S., Rittenhouse,S.E., Zvelebil,M.J.,
            Stein,R.C. and Waterfield,M.D.
  TITLE     Cloning of a human phosphoinositide 3-kinase with a C2 domain that
            displays reduced sensitivity to the inhibitor wortmannin
  JOURNAL   Biochem J 326 (Pt 1) (Pt 1), 139-147 (1997)
   PUBMED   9337861
REFERENCE   10 (bases 1 to 8428)
  AUTHORS   Milani,D., Mazzoni,M., Borgatti,P., Zauli,G., Cantley,L. and
            Capitani,S.
  TITLE     Extracellular human immunodeficiency virus type-1 Tat protein
            activates phosphatidylinositol 3-kinase in PC12 neuronal cells
  JOURNAL   J Biol Chem 271 (38), 22961-22964 (1996)
   PUBMED   8798481
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            BX642731.1, BC113658.1, BC040952.1, AC116533.11 and AL049998.1.
            
            On Jun 2, 2019 this sequence version replaced NM_002645.3.
            
            Summary: The protein encoded by this gene belongs to the
            phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in
            signaling pathways involved in cell proliferation, oncogenic
            transformation, cell survival, cell migration, and intracellular
            protein trafficking. This protein contains a lipid kinase catalytic
            domain as well as a C-terminal C2 domain, a characteristic of class
            II PI3-kinases. C2 domains act as calcium-dependent phospholipid
            binding motifs that mediate translocation of proteins to membranes,
            and may also mediate protein-protein interactions. The PI3-kinase
            activity of this protein is not sensitive to nanomolar levels of
            the inhibitor wortmanin. This protein was shown to be able to be
            activated by insulin and may be involved in integrin-dependent
            signaling. [provided by RefSeq, Jul 2008].
            
            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 :: SRR11853564.4519.1,
                                           SRR11853563.4986.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000691414.1/ ENSP00000509400.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-139               BX642731.1         20-158
            140-1442            BC113658.1         2-1304
            1443-1531           BC040952.1         1409-1497
            1532-5082           BC113658.1         1394-4944
            5083-7141           AC116533.11        66078-68136
            7142-8428           AL049998.1         4-1290
FEATURES             Location/Qualifiers
     source          1..8428
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11p15.1"
     gene            1..8428
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /note="phosphatidylinositol-4-phosphate 3-kinase catalytic
                     subunit type 2 alpha"
                     /db_xref="GeneID:5286"
                     /db_xref="HGNC:HGNC:8971"
                     /db_xref="MIM:603601"
     exon            1..139
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            140..1269
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     CDS             205..5265
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /EC_number="2.7.1.137"
                     /EC_number="2.7.1.154"
                     /EC_number="2.7.1.153"
                     /note="isoform 1 is encoded by transcript variant 1;
                     C2-containing phosphatidylinositol kinase;
                     phosphatidylinositol-4-phosphate 3-kinase C2
                     domain-containing subunit alpha; ptdIns-3-kinase C2
                     subunit alpha; phosphoinositide 3-kinase-C2-alpha;
                     phosphoinositide-3-kinase, class 2, alpha polypeptide"
                     /codon_start=1
                     /product="phosphatidylinositol 4-phosphate 3-kinase C2
                     domain-containing subunit alpha isoform 1"
                     /protein_id="NP_002636.2"
                     /db_xref="CCDS:CCDS7824.1"
                     /db_xref="GeneID:5286"
                     /db_xref="HGNC:HGNC:8971"
                     /db_xref="MIM:603601"
                     /translation="MAQISSNSGFKECPSSHPEPTRAKDVDKEEALQMEAEALAKLQK
                     DRQVTDNQRGFELSSSTRKKAQVYNKQDYDLMVFPESDSQKRALDIDVEKLTQAELEK
                     LLLDDSFETKKTPVLPVTPILSPSFSAQLYFRPTIQRGQWPPGLPGPSTYALPSIYPS
                     TYSKQAAFQNGFNPRMPTFPSTEPIYLSLPGQSPYFSYPLTPATPFHPQGSLPIYRPV
                     VSTDMAKLFDKIASTSEFLKNGKARTDLEITDSKVSNLQVSPKSEDISKFDWLDLDPL
                     SKPKVDNVEVLDHEEEKNVSSLLAKDPWDAVLLEERSTANCHLERKVNGKSLSVATVT
                     RSQSLNIRTTQLAKAQGHISQKDPNGTSSLPTGSSLLQEVEVQNEEMAAFCRSITKLK
                     TKFPYTNHRTNPGYLLSPVTAQRNICGENASVKVSIDIEGFQLPVTFTCDVSSTVEII
                     IMQALCWVHDDLNQVDVGSYVLKVCGQEEVLQNNHCLGSHEHIQNCRKWDTEIRLQLL
                     TFSAMCQNLARTAEDDETPVDLNKHLYQIEKPCKEAMTRHPVEELLDSYHNQVELALQ
                     IENQHRAVDQVIKAVRKICSALDGVETLAITESVKKLKRAVNLPRSKTADVTSLFGGE
                     DTSRSSTRGSLNPENPVQVSINQLTAAIYDLLRLHANSGRSPTDCAQSSKSVKEAWTT
                     TEQLQFTIFAAHGISSNWVSNYEKYYLICSLSHNGKDLFKPIQSKKVGTYKNFFYLIK
                     WDELIIFPIQISQLPLESVLHLTLFGILNQSSGSSPDSNKQRKGPEALGKVSLPLFDF
                     KRFLTCGTKLLYLWTSSHTNSVPGTVTKKGYVMERIVLQVDFPSPAFDIIYTTPQVDR
                     SIIQQHNLETLENDIKGKLLDILHKDSSLGLSKEDKAFLWEKRYYCFKHPNCLPKILA
                     SAPNWKWVNLAKTYSLLHQWPALYPLIALELLDSKFADQEVRSLAVTWIEAISDDELT
                     DLLPQFVQALKYEIYLNSSLVQFLLSRALGNIQIAHNLYWLLKDALHDVQFSTRYEHV
                     LGALLSVGGKRLREELLKQTKLVQLLGGVAEKVRQASGSARQVVLQRSMERVQSFFQK
                     NKCRLPLKPSLVAKELNIKSCSFFSSNAVPLKVTMVNADPMGEEINVMFKVGEDLRQD
                     MLALQMIKIMDKIWLKEGLDLRMVIFKCLSTGRDRGMVELVPASDTLRKIQVEYGVTG
                     SFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTG
                     HMFHIDFGKFLGHAQMFGSFKRDRAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAY
                     NLIRKQTNLFLNLLSLMIPSGLPELTSIQDLKYVRDALQPQTTDAEATIFFTRLIESS
                     LGSIATKFNFFIHNLAQLRFSGLPSNDEPILSFSPKTYSFRQDGRIKEVSVFTYHKKY
                     NPDKHYIYVVRILREGQIEPSFVFRTFDEFQELHNKLSIIFPLWKLPGFPNRMVLGRT
                     HIKDVAAKRKIELNSYLQSLMNASTDVAECDLVCTFFHPLLRDEKAEGIARSADAGSF
                     SPTPGQIGGAVKLSISYRNGTLFIMVMHIKDLVTEDGADPNPYVKTYLLPDNHKTSKR
                     KTKISRKTRNPTFNEMLVYSGYSKETLRQRELQLSVLSAESLRENFFLGGVTLPLKDF
                     NLSKETVKWYQLTAATYL"
     exon            1270..1373
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1374..1531
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1532..1652
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1653..1764
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1765..1844
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1845..1908
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            1909..2052
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2053..2101
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2102..2312
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2313..2435
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2436..2603
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2604..2715
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2716..2861
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            2862..3050
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            3051..3144
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            3145..3239
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            3240..3420
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            3421..3525
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            3526..3618
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            3619..3748
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            3749..3885
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            3886..4055
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            4056..4212
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            4213..4322
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            4323..4530
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            4531..4655
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            4656..4773
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            4774..4846
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            4847..4956
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            4957..5082
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     exon            5083..8428
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /inference="alignment:Splign:2.1.0"
     regulatory      8422..8427
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /note="hexamer: AATAAA"
     polyA_site      8428
                     /gene="PIK3C2A"
                     /gene_synonym="CPK; OCSKD; PI3-K-C2(ALPHA); PI3-K-C2A;
                     PI3K-C2-alpha; PI3K-C2alpha"
                     /note="major polyA site"
ORIGIN      
        1 gacgtgctgc gcttggctgg ctgtggagtc ggccgaagct ttcggcggcg gctgagccag
       61 ctgaggggaa aaatggctcg gactgtggcg gcttcggcgg ctcaggttgt ggtagaggcg
      121 gaggctcagg cagcttgagg ccttgctatt ttggaagcta caagaaaaaa atagaggaag
      181 gaaggtttgg tctttttagt ggacatggct cagatatcta gcaacagcgg atttaaagaa
      241 tgtccatctt cacatccgga accaacaaga gcaaaagatg tggacaaaga agaagcatta
      301 cagatggaag cagaggcttt agcaaaactg caaaaggata gacaagtgac tgacaatcag
      361 agaggctttg agttgtcaag cagcaccaga aaaaaagcac aggtttataa caagcaggat
      421 tatgatctca tggtgtttcc tgaatcagat tcccaaaaaa gagcattaga tattgatgta
      481 gaaaagctca cccaagctga acttgagaaa ctattgctgg atgacagttt cgagactaaa
      541 aaaacacctg tattaccagt tactcctatt ctgagccctt ccttttcagc acagctctat
      601 tttagaccta ctattcagag aggacagtgg ccacctggat tacctgggcc ttccacttat
      661 gctttacctt ctatttatcc ttctacttac agtaaacagg ctgcattcca aaatggcttc
      721 aatccaagaa tgcccacttt tccatctaca gaacctatat atttaagtct tccgggacaa
      781 tctccatatt tctcatatcc tttgacacct gccacaccct ttcatccaca aggaagctta
      841 cctatctatc gtccagtagt cagtactgac atggcaaaac tatttgacaa aatagctagt
      901 acatcagaat ttttaaaaaa tgggaaagca aggactgatt tggagataac agattcaaaa
      961 gtcagcaatc tacaggtatc tccaaagtct gaggatatca gtaaatttga ctggttagac
     1021 ttggatcctc taagtaagcc taaggtggat aatgtggagg tattagacca tgaggaagag
     1081 aaaaatgttt caagtttgct agcaaaggat ccttgggatg ctgttcttct tgaagagaga
     1141 tcgacagcaa attgtcatct tgaaagaaag gtgaatggaa aatccctttc tgtggcaact
     1201 gttacaagaa gccagtcttt aaatattcga acaactcagc ttgcaaaagc ccagggccat
     1261 atatctcaga aagacccaaa tgggaccagt agtttgccaa ctggaagttc tcttcttcaa
     1321 gaagttgaag tacagaatga ggagatggca gctttttgtc gatccattac aaaattgaag
     1381 accaaatttc catataccaa tcaccgcaca aacccaggct atttgttaag tccagtcaca
     1441 gcacaaagaa acatatgcgg agaaaatgct agtgtgaagg tctccattga cattgaagga
     1501 tttcagctac cagttacttt tacgtgtgat gtgagttcta ctgtagaaat cattataatg
     1561 caagcccttt gctgggtaca tgatgacttg aatcaagtag atgttggcag ctatgttcta
     1621 aaagtttgtg gtcaagagga agtgctgcag aataatcatt gccttggaag tcatgagcat
     1681 attcaaaact gtcgaaaatg ggacacagaa attagactac aactcttgac cttcagtgca
     1741 atgtgtcaaa atctggcccg aacagcagaa gatgatgaaa cacccgtgga tttaaacaaa
     1801 cacctgtatc aaatagaaaa accttgcaaa gaagccatga cgagacaccc tgttgaagaa
     1861 ctcttagatt cttatcacaa ccaagtagaa ctggctcttc aaattgaaaa ccaacaccga
     1921 gcagtagatc aagtaattaa agctgtaaga aaaatctgta gtgctttaga tggtgtcgag
     1981 actcttgcca ttacagaatc agtaaagaag ctaaagagag cagttaatct tccaaggagt
     2041 aaaactgctg atgtgacttc tttgtttgga ggagaagaca ctagcaggag ttcaactagg
     2101 ggctcactta atcctgaaaa tcctgttcaa gtaagcataa accaattaac tgcagcaatt
     2161 tatgatcttc tcagactcca tgcaaattct ggtaggagtc ctacagactg tgcccaaagt
     2221 agcaagagtg tcaaggaagc atggactaca acagagcagc tccagtttac tatttttgct
     2281 gctcatggaa tttcaagtaa ttgggtatca aattatgaaa aatactactt gatatgttca
     2341 ctgtctcaca atggaaagga tctttttaaa cctattcaat caaagaaggt tggcacttac
     2401 aagaatttct tctatcttat taaatgggat gaactaatca tttttcctat ccagatatca
     2461 caattgccat tagaatcagt tcttcacctt actctttttg gaattttaaa tcagagcagt
     2521 ggaagttccc ctgattctaa taagcagaga aagggaccag aagctttggg caaagtttct
     2581 ttacctcttt ttgactttaa acggttttta acatgtggaa ctaaacttct atatctttgg
     2641 acttcatcac atacaaattc tgttcctgga acagttacca aaaaaggata tgtcatggaa
     2701 agaatagtgc tacaggttga ttttccttct cctgcatttg atattattta tacaactcct
     2761 caagttgaca gaagcattat acagcaacat aacttagaaa cactagagaa tgatataaaa
     2821 gggaaacttc ttgatattct tcataaagac tcatcacttg gactttctaa agaagataaa
     2881 gcttttttat gggagaaacg ttattattgc ttcaaacacc caaattgtct tcctaaaata
     2941 ttagcaagcg ccccaaactg gaaatgggtt aatcttgcca aaacttactc attgcttcac
     3001 cagtggcctg cattgtaccc actaattgca ttggaacttc ttgattcaaa atttgctgat
     3061 caggaagtaa gatccctagc tgtgacctgg attgaggcca ttagtgatga tgagctaaca
     3121 gatcttcttc cacagtttgt acaagctttg aaatatgaaa tttacttgaa tagttcatta
     3181 gtgcaattcc ttttgtccag ggcattggga aatatccaga tagcacacaa tttatattgg
     3241 cttctcaaag atgccctgca tgatgtacag tttagtaccc gatacgaaca tgttttgggt
     3301 gctctcctgt cagtaggagg aaaacgactt agagaagaac ttctaaaaca gacgaaactt
     3361 gtacagcttt taggaggagt agcagaaaaa gtaaggcagg ctagtggatc agccagacag
     3421 gttgttctcc aaagaagtat ggaacgagta cagtcctttt ttcagaaaaa taaatgccgt
     3481 ctccctctca agccaagtct agtggcaaaa gaattaaata ttaagtcgtg ttccttcttc
     3541 agttctaatg ctgtccccct aaaagtcaca atggtgaatg ctgaccctat gggagaagaa
     3601 attaatgtca tgtttaaggt tggtgaagat cttcggcaag atatgttagc tttacagatg
     3661 ataaagatta tggataagat ctggcttaaa gaaggactag atctgaggat ggtaattttc
     3721 aaatgtctct caactggcag agatcgaggc atggtggagc tggttcctgc ttccgatacc
     3781 ctcaggaaaa tccaagtgga atatggtgtg acaggatcct ttaaagataa accacttgca
     3841 gagtggctaa ggaaatacaa tccctctgaa gaagaatatg aaaaggcttc agagaacttt
     3901 atctattcct gtgctggatg ctgtgtagcc acctatgttt taggcatctg tgatcgacac
     3961 aatgacaata taatgcttcg aagcacggga cacatgtttc acattgactt tggaaagttt
     4021 ttgggacatg cacagatgtt tggcagcttc aaaagggatc gggctccttt tgtgctgacc
     4081 tctgatatgg catatgtcat taatgggggt gaaaagccca ccattcgttt tcagttgttt
     4141 gtggacctct gctgtcaggc ctacaacttg ataagaaagc agacaaacct ttttcttaac
     4201 ctcctttcac tgatgattcc ttcagggtta ccagaactta caagtattca agatttgaaa
     4261 tacgttagag atgcacttca accccaaact acagacgcag aagctacaat tttctttact
     4321 aggcttattg aatcaagttt gggaagcatt gccacaaagt ttaacttctt cattcacaac
     4381 cttgctcagc ttcgtttttc tggtcttcct tctaatgatg agcccatcct ttcattttca
     4441 cctaaaacat actcctttag acaagatggt cgaatcaagg aagtctctgt ttttacatat
     4501 cataagaaat acaacccaga taaacattat atttatgtag tccgaatttt gagggaagga
     4561 cagattgaac catcatttgt cttccgaaca tttgacgaat ttcaggaact tcacaataag
     4621 ctcagtatta tttttccact ttggaagtta ccaggctttc ctaataggat ggttctagga
     4681 agaacacaca taaaagatgt agcagccaaa aggaaaattg agttaaacag ttacttacag
     4741 agtttgatga atgcttcaac ggatgtagca gagtgtgatc ttgtttgtac tttcttccac
     4801 cctttacttc gtgatgagaa agctgaaggg atagctaggt ctgcagatgc aggttccttc
     4861 agtcctactc caggccaaat aggaggagct gtgaaattat ccatctctta ccgaaatggt
     4921 actcttttca tcatggtgat gcatatcaaa gatcttgtta ctgaagatgg agctgaccca
     4981 aatccatatg tcaaaacata cctacttcca gataaccaca aaacatccaa acgtaaaacc
     5041 aaaatttcac gaaaaacgag gaatccgaca ttcaatgaaa tgcttgtata cagtggatat
     5101 agcaaagaaa ccctaagaca gcgagaactt caactaagtg tactcagtgc agaatctctg
     5161 cgggagaatt ttttcttggg tggagtaacc ctgcctttga aagatttcaa cttgagcaaa
     5221 gagacggtta aatggtatca gctgactgcg gcaacatact tgtaaactag tgaatgtttg
     5281 agctttggaa gcatgaacag ttataaacgt gcatgcatac atgcacacac acacagacac
     5341 acacacacac acttgttaat tttgtatagt atttttatac ttggacagaa cttataaagt
     5401 taaatatact tgctgcattt caacacatct gttggaccaa cagtcacata actaaccttt
     5461 ttgaattttt ggaagccatt gctgttttaa agtcattatg tagaatgcta caaaccctaa
     5521 acttaatata tactaattcc tgaaaaagac tttgagacag tactatgtca gttcagccac
     5581 ctattttgca ttgttttcta taaggaggca aagcatatgt gttttcctgt tatgcacctt
     5641 ttatagcctt taccactgtg taatgttcac aaacaccaaa gtaaaggaaa aatgcaggat
     5701 gttaccgtaa aatccagctg ctattcatgg agctgaaaaa caaagcacaa ataatagata
     5761 gctaagttaa gaactactaa gtagtttata gaagtaggga aaaacgtaat actgcttttt
     5821 attcatgtct ttaaagcctt tttcagaata agtgccaatc actgatgttg taaataatgg
     5881 tgccttaact ttatatgctt ccctggcact tcgtttctga tttttttcct gatttgataa
     5941 ataattagta catagttttc actcacttgc agcttactaa agacaagaaa ttatgtacat
     6001 gtactaatgt ttttcccaca aaaaaatcct ttacttctga tgtatgaatt agttatctaa
     6061 atagttaagc ctaatacctg aataagactc accaatgtga ttgtacaata aattctatca
     6121 ttccattaaa atcctacatt tattcccagg aatggtaatt tcacctccct acatctatac
     6181 tccactccct cagtaaataa gtgaaaattg ttaacccatg tgcccattcc tgagtagggc
     6241 agactcttca caagaggccc atgacaagaa ttctagggtc cagattgaac tttaatatag
     6301 acctttgtct gtgtagacca gtttgtcttg taaactgtct tacttatgtg tgtaaacatt
     6361 ttacattcac atgaaaagtt attttccttt atataattgg attcagaatc ataagggaca
     6421 ggactgaaat tattctacag taaccagtaa gaataagatt cggccgggca cggtggctcc
     6481 tgcctgtaat cccaacactt tgggaggcca aggtgggcgg atcacctgag gtcaggagtt
     6541 tgagaccagc ctggccaaca tggtgaaacc ccgtctctac acaaaaatta gccaggcgtg
     6601 gtagcgggca tctgtaatcc cagctacttg gggggctgag gcaggagaat cgcttgaacc
     6661 caggaggcgg aggttgcagt gagccgagat cacgccactg cactcccgcc tgggtgacaa
     6721 gagcaaaact ccatcttaaa aaaaaagaaa aaaagagtaa gattcatttt tattagttac
     6781 tcaacttcag acacaatttt gttaatttgg atatatacat atatataata agaactcatg
     6841 gttagaatag aaatacagat actttaaaaa tggtaataga aattgtacca atcaggttgc
     6901 tgtgagaaaa ctgacaaaat atgcaataaa gaataccaag agagaaagga caatcgccaa
     6961 ttcagtttcc cagaacagaa tttttatgaa ctgcacaaat gtttaatgta aatggtgata
     7021 cctacaggga agaaatagaa gagttgataa tatatcactg ggacggggtg ggggaaagac
     7081 ttgaaatttt tggtgcctaa cactaatggt ccatatgtag ttaaacccat gagtatggta
     7141 tatgaatgtc ttttttaaat gttaaaatgt gttgtctatt taatgttaat taaaatgcag
     7201 atcaaagcac caccatttgc tttttccaca gatcattaac atttccttaa agtatgtaag
     7261 tacctttgca aatgcaaatg tactagtaat tttcacttaa gcttttgaga ccgaattcca
     7321 ttccaccagt tatcacttag ccactgtaat ttaaaaacaa acaaacaaac aaaaactgtc
     7381 ttggtagagg tcgttaatta gactcaacat gtactgcctt tttgcagtct attatgacag
     7441 tgtcttttag cacaaataat agagctaaaa aatgtcctgt cacttccatt ataagaaatc
     7501 tggattcata tctaagtgta tattataata ctgtacagtt aagagttcag aacaagtggt
     7561 aatgttttct cttaatttaa ctcattttgt gccttcttta ctcattcaaa cacacataca
     7621 ttttacatat agtttatttc tttatgaaat gctaatcttc agcccgtacc aaaaagtaga
     7681 gtggagcctc tttgcactac tactatcaat aaattttaaa tcagttggat ttttaagcat
     7741 tttttaaaag ctgacattaa agtaaatcta aaaaaagttt aacaaactgg ccaagacact
     7801 aatttttatg tataatcaca atattttata ctcaccttta ttgactaaaa ataattatgc
     7861 tacatgttgt cctgcatcag aagaattatt tcttcttgcc agtgttttgg gatttgaaga
     7921 taatggttca ctcaaagaac ctattatttt ctctactgag gaacccaatg tagaacttgc
     7981 actgatattt ttattactgc ctttatatga atctataggt atctaaatgt taaggcatgt
     8041 atgatctttg atcatttctt ttttcaaatt aaagttgtat aaaagtttca atatcttgcc
     8101 ttaaattagt tgcctattct ttctaggatt caaatattgt gacatttaaa aaagaaaaca
     8161 ttcacttttg aaacttagac ttcagatcaa aaaggactga acccccacta tcataatcca
     8221 tacattcatt tccatgttgt ttgactagca gtgcatatat gaatgaatat ggtaattaat
     8281 cttacctata agaaccaaat actttaatta tattaagata gtgaataaag atgtataata
     8341 tttttattaa taccttgaat atattcagtg gattgaatgt gacttcataa ctgtactacg
     8401 attgtattaa aatatttctg gaataaaa
//
