LOCUS       NM_016341              12481 bp    mRNA    linear   PRI 29-OCT-2024
DEFINITION  Homo sapiens phospholipase C epsilon 1 (PLCE1), transcript variant
            1, mRNA.
ACCESSION   NM_016341 XM_001124973
VERSION     NM_016341.4
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 12481)
  AUTHORS   Fan,Y., Hao,Y., Zhu,C., Hu,B., Ma,R., Liu,Y. and Li,G.
  TITLE     PLCepsilon promotes the Warburg effect and tumorigenesis through
            AKT/GSK3beta/Cdc25a in bladder cancer
  JOURNAL   Biotechnol Genet Eng Rev 40 (3), 2155-2169 (2024)
   PUBMED   37018449
  REMARK    GeneRIF: PLCepsilon promotes the Warburg effect and tumorigenesis
            through AKT/GSK3beta/Cdc25a in bladder cancer.
REFERENCE   2  (bases 1 to 12481)
  AUTHORS   Gupta,A., Thirunavukkarasu,S., Rangel-Moreno,J., Ahmed,M.,
            Swanson,R.V., Mbandi,S.K., Smrcka,A.V., Kaushal,D., Scriba,T.J. and
            Khader,S.A.
  TITLE     Phospholipase C epsilon-1 (PLCE1) mediates macrophage activation
            and protection against tuberculosis
  JOURNAL   Infect Immun 92 (4), e0049523 (2024)
   PUBMED   38451080
  REMARK    GeneRIF: Phospholipase C epsilon-1 (PLCE1) mediates macrophage
            activation and protection against tuberculosis.
REFERENCE   3  (bases 1 to 12481)
  AUTHORS   Pantel,D., Mertens,N.D., Schneider,R., Holzel,S., Kari,J.A.,
            Desoky,S.E., Shalaby,M.A., Lim,T.Y., Sanna-Cherchi,S., Shril,S. and
            Hildebrandt,F.
  TITLE     Copy number variation analysis in 138 families with
            steroid-resistant nephrotic syndrome identifies causal homozygous
            deletions in PLCE1 and NPHS2 in two families
  JOURNAL   Pediatr Nephrol 39 (2), 455-461 (2024)
   PUBMED   37670083
  REMARK    GeneRIF: Copy number variation analysis in 138 families with
            steroid-resistant nephrotic syndrome identifies causal homozygous
            deletions in PLCE1 and NPHS2 in two families.
REFERENCE   4  (bases 1 to 12481)
  AUTHORS   Gao,X.R., Pan,J.J., Nie,W.J., Li,X.Y. and Zhang,S.L.
  TITLE     Association between the Missense Variant of PLCE1 and the Risk of
            Colorectal Cancer
  JOURNAL   Biomed Environ Sci 36 (1), 109-111 (2023)
   PUBMED   36650688
  REMARK    GeneRIF: Association between the Missense Variant of PLCE1 and the
            Risk of Colorectal Cancer.
REFERENCE   5  (bases 1 to 12481)
  AUTHORS   Atchison,D.K., O'Connor,C.L., Converso-Baran,K., Bergin,I.L.,
            Zhang,H., Wang,Y., Hartman,J.R., Ju,W., Smrcka,A.V., Ganesh,S.K.
            and Bitzer,M.
  TITLE     Phospholipase Cepsilon insufficiency causes ascending aortic
            aneurysm and dissection
  JOURNAL   Am J Physiol Heart Circ Physiol 323 (6), H1376-H1387 (2022)
   PUBMED   36367690
  REMARK    GeneRIF: Phospholipase Cepsilon insufficiency causes ascending
            aortic aneurysm and dissection.
REFERENCE   6  (bases 1 to 12481)
  AUTHORS   Mayne,M., Holden,C.P., Nath,A. and Geiger,J.D.
  TITLE     Release of calcium from inositol 1,4,5-trisphosphate
            receptor-regulated stores by HIV-1 Tat regulates TNF-alpha
            production in human macrophages
  JOURNAL   J Immunol 164 (12), 6538-6542 (2000)
   PUBMED   10843712
REFERENCE   7  (bases 1 to 12481)
  AUTHORS   Haughey,N.J., Holden,C.P., Nath,A. and Geiger,J.D.
  TITLE     Involvement of inositol 1,4,5-trisphosphate-regulated stores of
            intracellular calcium in calcium dysregulation and neuron cell
            death caused by HIV-1 protein tat
  JOURNAL   J Neurochem 73 (4), 1363-1374 (1999)
   PUBMED   10501179
REFERENCE   8  (bases 1 to 12481)
  AUTHORS   Mayne,M., Bratanich,A.C., Chen,P., Rana,F., Nath,A. and Power,C.
  TITLE     HIV-1 tat molecular diversity and induction of TNF-alpha:
            implications for HIV-induced neurological disease
  JOURNAL   Neuroimmunomodulation 5 (3-4), 184-192 (1998)
   PUBMED   9730685
REFERENCE   9  (bases 1 to 12481)
  AUTHORS   Chen,P., Mayne,M., Power,C. and Nath,A.
  TITLE     The Tat protein of HIV-1 induces tumor necrosis factor-alpha
            production. Implications for HIV-1-associated neurological diseases
  JOURNAL   J Biol Chem 272 (36), 22385-22388 (1997)
   PUBMED   9278385
REFERENCE   10 (bases 1 to 12481)
  AUTHORS   Zauli,G., Previati,M., Caramelli,E., Bassini,A., Falcieri,E.,
            Gibellini,D., Bertolaso,L., Bosco,D., Robuffo,I. and Capitani,S.
  TITLE     Exogenous human immunodeficiency virus type-1 Tat protein
            selectively stimulates a phosphatidylinositol-specific
            phospholipase C nuclear pathway in the Jurkat T cell line
  JOURNAL   Eur J Immunol 25 (9), 2695-2700 (1995)
   PUBMED   7589147
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL365510.32, AB040949.2,
            AK074239.1, AF117948.1, AL139124.12 and AL355341.19.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_016341.3.
            
            Summary: This gene encodes a phospholipase enzyme that catalyzes
            the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate
            two second messengers: inositol 1,4,5-triphosphate (IP3) and
            diacylglycerol (DAG). These second messengers subsequently regulate
            various processes affecting cell growth, differentiation, and gene
            expression. This enzyme is regulated by small monomeric GTPases of
            the Ras and Rho families and by heterotrimeric G proteins. In
            addition to its phospholipase C catalytic activity, this enzyme has
            an N-terminal domain with guanine nucleotide exchange (GEF)
            activity. Mutations in this gene cause early-onset nephrotic
            syndrome; characterized by proteinuria, edema, and diffuse
            mesangial sclerosis or focal and segmental glomerulosclerosis.
            Alternative splicing results in multiple transcript variants
            encoding distinct isoforms.[provided by RefSeq, Sep 2009].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1; also known as
            PLCepsilon1a).
            
            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 :: BC151854.1, AB040949.2 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1970526
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000371380.8/ ENSP00000360431.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-58                AL365510.32        79236-79293
            59-6471             AB040949.2         1-6413
            6472-7625           AK074239.1         801-1954
            7626-8047           AB040949.2         7568-7989
            8048-8050           AF117948.1         4060-4062
            8051-9339           AL139124.12        91988-93276
            9340-12481          AL355341.19        2001-5142
FEATURES             Location/Qualifiers
     source          1..12481
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10q23.33"
     gene            1..12481
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /note="phospholipase C epsilon 1"
                     /db_xref="GeneID:51196"
                     /db_xref="HGNC:HGNC:17175"
                     /db_xref="MIM:608414"
     exon            1..328
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            329..1898
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     CDS             693..7601
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /EC_number="3.1.4.11"
                     /note="isoform 1 is encoded by transcript variant 1;
                     pancreas-enriched phospholipase C; phosphoinositide
                     phospholipase C; phosphoinositide-specific phospholipase C
                     epsilon-1; PLC-epsilon-1; phosphoinositide phospholipase
                     C-epsilon-1; 1-phosphatidylinositol 4,5-bisphosphate
                     phosphodiesterase epsilon-1"
                     /codon_start=1
                     /product="1-phosphatidylinositol 4,5-bisphosphate
                     phosphodiesterase epsilon-1 isoform 1"
                     /protein_id="NP_057425.3"
                     /db_xref="CCDS:CCDS41552.1"
                     /db_xref="GeneID:51196"
                     /db_xref="HGNC:HGNC:17175"
                     /db_xref="MIM:608414"
                     /translation="MTSEEMTASVLIPVTQRKVVSAQSAADESSEKVSDINISKAHTV
                     RRSGETSHTISQLNKLKEEPSGSNLPKILSIAREKIVSDENSNEKCWEKIMPDSAKNL
                     NINCNNILRNHQHGLPQRQFYEMYNSVAEEDLCLETGIPSPLERKVFPGIQLELDRPS
                     MGISPLGNQSVIIETGRAHPDSRRAVFHFHYEVDRRMSDTFCTLSENLILDDCGNCVP
                     LPGGEEKQKKNYVAYTCKLMELAKNCDNKNEQLQCDHCDTLNDKYFCFEGSCEKVDMV
                     YSGDSFCRKDFTDSQAAKTFLSHFEDFPDNCDDVEEDAFKSKKERSTLLVRRFCKNDR
                     EVKKSVYTGTRAIVRTLPSGHIGLTAWSYIDQKRNGPLLPCGRVMEPPSTVEIRQDGS
                     QRLSEAQWYPIYNAVRREETENTVGSLLHFLTKLPASETAHGRISVGPCLKQCVRDTV
                     CEYRATLQRTSISQYITGSLLEATTSLGARSGLLSTFGGSTGRMMLKERQPGPSVANS
                     NALPSSSAGISKELIDLQPLIQFPEEVASILMEQEQTIYRRVLPVDYLCFLTRDLGTP
                     ECQSSLPCLKASISASILTTQNGEHNALEDLVMRFNEVSSWVTWLILTAGSMEEKREV
                     FSYLVHVAKCCWNMGNYNAVMEFLAGLRSRKVLKMWQFMDQSDIETMRSLKDAMAQHE
                     SSCEYRKVVTRALHIPGCKVVPFCGVFLKELCEVLDGASGLMKLCPRYNSQEETLEFV
                     ADYSGQDNFLQRVGQNGLKNSEKESTVNSIFQVIRSCNRSLETDEEDSPSEGNSSRKS
                     SLKDKSRWQFIIGDLLDSDNDIFEQSKEYDSHGSEDSQKAFDHGTELIPWYVLSIQAD
                     VHQFLLQGATVIHYDQDTHLSARCFLQLQPDNSTLTWVKPTTASPASSKAKLGVLNNT
                     AEPGKFPLLGNAGLSSLTEGVLDLFAVKAVYMGHPGIDIHTVCVQNKLGSMFLSETGV
                     TLLYGLQTTDNRLLHFVAPKHTAKMLFSGLLELTRAVRKMRKFPDQRQQWLRKQYVSL
                     YQEDGRYEGPTLAHAVELFGGRRWSARNPSPGTSAKNAEKPNMQRNNTLGISTTKKKK
                     KILMRGESGEVTDDEMATRKAKMHKECRSRSGSDPQDINEQEESEVNAIANPPNPLPS
                     RRAHSLTTAGSPNLAAGTSSPIRPVSSPVLSSSNKSPSSAWSSSSWHGRIKGGMKGFQ
                     SFMVSDSNMSFVEFVELFKSFSVRSRKDLKDLFDVYAVPCNRSGSESAPLYTNLTIDE
                     NTSDLQPDLDLLTRNVSDLGLFIKSKQQLSDNQRQISDAIAAASIVTNGTGIESTSLG
                     IFGVGILQLNDFLVNCQGEHCTYDEILSIIQKFEPSISMCHQGLMSFEGFARFLMDKE
                     NFASKNDESQENIKELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSV
                     ELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSAFINSDLPIIISIENHCSLPQQ
                     RKMAEIFKTVFGEKLVTKFLFETDFSDDPMLPSPDQLRKKVLLKNKKLKAHQTPVDIL
                     KQKAHQLASMQVQAYNGGNANPRPANNEEEEDEEDEYDYDYESLSDDNILEDRPENKS
                     CNDKLQFEYNEEIPKRIKKADNSACNKGKVYDMELGEEFYLDQNKKESRQIAPELSDL
                     VIYCQAVKFPGLSTLNASGSSRGKERKSRKSIFGNNPGRMSPGETASFNKTSGKSSCE
                     GIRQTWEESSSPLNPTTSLSAIIRTPKCYHISSLNENAAKRLCRRYSQKLTQHTACQL
                     LRTYPAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEANGGCGYVLKP
                     PVLWDKNCPMYQKFSPLERDLDSMDPAVYSLTIVSGQNVCPSNSMGSPCIEVDVLGMP
                     LDSCHFRTKPIHRNTLNPMWNEQFLFHVHFEDLVFLRFAVVENNSSAVTAQRIIPLKA
                     LKRGYRHLQLRNLHNEVLEISSLFINSRRMEENSSGNTMSASSMFNTEERKCLQTHRV
                     TVHGVPGPEPFTVFTINGGTKAKQLLQQILTNEQDIKPVTTDYFLMEEKYFISKEKNE
                     CRKQPFQRAIGPEEEIMQILSSWFPEEGYMGRIVLKTQQENLEEKNIVQDDKEVILSS
                     EEESFFVQVHDVSPEQPRTVIKAPRVSTAQDVIQQTLCKAKYSYSILSNPNPSDYVLL
                     EEVVKDTTNKKTTTPKSSQRVLLDQECVFQAQSKWKGAGKFILKLKEQVQASREDKKK
                     GISFASELKKLTKSTKQPRGLTSPSQLLTSESIQTKEEKPVGGLSSSDTMDYRQ"
     exon            1899..2184
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            2185..2501
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            2502..2647
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            2648..2906
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            2907..3112
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            3113..3788
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            3789..3971
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            3972..4089
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            4090..4246
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            4247..4369
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            4370..4506
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            4507..4745
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            4746..4807
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            4808..4973
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            4974..5081
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            5082..5198
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            5199..5357
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            5358..5487
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            5488..5609
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            5610..5727
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            5728..5859
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            5860..6150
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            6151..6314
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            6315..6576
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            6577..6695
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            6696..6824
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            6825..7034
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            7035..7193
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            7194..7412
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            7413..7625
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     exon            7626..12481
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /inference="alignment:Splign:2.1.0"
     regulatory      8023..8028
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /note="hexamer: AATAAA"
     polyA_site      8050
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /note="major polyA site"
     regulatory      8951..8956
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /note="hexamer: AATGAA"
     polyA_site      8980
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
     regulatory      9030..9035
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /note="hexamer: ATTACA"
     polyA_site      9050
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
     regulatory      12340..12345
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /note="hexamer: ATTAAA"
     polyA_site      12365
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
     regulatory      12460..12465
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
                     /note="hexamer: AATAAA"
     polyA_site      12481
                     /gene="PLCE1"
                     /gene_synonym="NPHS3; PLCE; PPLC"
ORIGIN      
        1 gggcagcgcg cacatctcgg cgggagcgga ctgtgaacgg cgcgggtcca cacggtaacg
       61 ctgggcaacg tgggcaacgc ggcgggcggc gggctcgcgc ggcgggaggg gcagcggcgg
      121 cgcgcccggg ctctacctcc cgggctctgc ctcccgggct ctgcctctcg ggcacttgcc
      181 tggctcctgc gcgttcctgg gcatcggctc tgcagctgac acacagtagc ggggacaccc
      241 gacgccgcta gcgacaggcg cgcggacggc tggtcccaga gggacgctgc gcttggggac
      301 gccggcgaga ctcgccagga gccaagagga aacaggaatc attcaaactg gattttaaaa
      361 tcattgcaaa tcagtgatgg atcagaagtt gcagagtgca atcccgagta aaagtcttca
      421 aaaaattttg cttcaggtaa cagaggaagg aaaattgatc taccacctta aaaccctgat
      481 ctagaaaaaa tatatattca tgataggaag ttataactaa gaaaatttat ttgcctctta
      541 atgctcctga atgaaaggaa ttatcccttt gttctttggg aggacttgtg tatctgagat
      601 tgttgtaata atcagtcatt ttattaaaac cttgacatga tcaccaggga ggaaaaatag
      661 agcaatagtc aaaacctgtg tgttagtcca agatgacttc tgaagaaatg acagcttctg
      721 ttctcatacc tgtgactcag agaaaagtgg tttctgccca gtcggctgca gatgaaagta
      781 gtgaaaaggt ctcagacatc aatatttcaa aagcacatac tgtcagacga agtggggaga
      841 cttctcatac catctcacaa ctgaacaaac ttaaagaaga accttctgga agcaacttgc
      901 caaagattct ctcaatagcg agggagaaaa tagtgagtga tgagaacagt aatgaaaaat
      961 gttgggagaa aatcatgcca gattctgcga aaaaccttaa cattaactgc aacaacatat
     1021 tgagaaacca tcagcatggc cttcctcaga gacaatttta tgaaatgtac aactctgttg
     1081 ctgaggaaga cttgtgttta gaaactggaa ttccttctcc actggaaaga aaggtgttcc
     1141 ctggaattca actggaacta gacagacctt ccatgggcat tagtccttta ggaaatcagt
     1201 cagtgatcat agagacaggc agagcacacc ctgacagcag aagggcagta tttcattttc
     1261 attatgaagt tgacagaaga atgtcagaca ctttctgtac cctatcagaa aacttaattt
     1321 tagacgattg tggaaattgt gtaccactac ctgggggtga ggagaagcaa aagaaaaact
     1381 atgtggcata tacctgtaaa ctgatggaat tggccaaaaa ttgtgataat aagaatgagc
     1441 agctgcagtg tgatcattgt gacaccttga atgataaata cttttgcttt gaaggctctt
     1501 gtgagaaggt tgacatggta tattcaggtg atagcttttg taggaaagac tttactgaca
     1561 gtcaagctgc caagaccttt ttgagccatt ttgaggactt ccctgataat tgtgatgatg
     1621 tagaagaaga cgcttttaaa agcaaaaagg agcgatccac tttgttagtc aggagattct
     1681 gtaaaaatga cagagaagtt aagaaatctg tgtatactgg aacaagagca attgtgagaa
     1741 ctctgccttc tggccacatt gggctgactg catggagtta catagatcag aagagaaatg
     1801 gtcccttact gccttgtggg agagtaatgg aacccccgtc aacagtggag ataaggcaag
     1861 atgggagcca acgtctgtca gaagcccagt ggtatcctat ctacaatgca gtgagaagag
     1921 aagaaacaga aaatacagtt ggatctctac tccatttcct caccaagctc ccagcctccg
     1981 agacagccca tggaaggata agcgttggtc catgcttaaa gcaatgtgtc cgagacactg
     2041 tatgtgagta tcgcgccacc ctccaaagga cttcaatatc gcagtacatc accggttctc
     2101 tcctagaagc aaccacgtct ttgggagcaa gaagtggcct tctcagtact tttggaggat
     2161 ccactggacg aatgatgctg aaagaacgcc agccaggccc ctctgtggcc aattccaatg
     2221 ccctcccttc aagttcagct gggatcagca aggagctgat cgatctgcag cctctcatcc
     2281 agttcccaga ggaagtcgcc agcatcctga tggagcaaga gcagactatt taccgcaggg
     2341 tcttgccagt cgactacctt tgcttcttaa cacgggactt gggcactcct gaatgccaga
     2401 gctccttgcc ctgcctcaaa gcatccatct cagcgtcgat tcttaccact cagaatggag
     2461 agcacaatgc ccttgaagat ctggtgatga ggtttaatga ggtgagctcc tgggtgacat
     2521 ggctgatcct cacggcaggc tccatggagg agaagcgaga agtcttttca tatttggtgc
     2581 atgtggccaa atgctgctgg aacatgggca actacaacgc tgtcatggag ttcttggctg
     2641 gcctcaggtc aagaaaagtt ttaaaaatgt ggcagttcat ggaccagtct gatattgaga
     2701 ccatgaggag cctgaaggat gctatggccc agcatgagtc ctcttgtgag tacagaaagg
     2761 tggtgacacg tgccctgcac atccctggct gtaaggtggt tccattctgt ggggtgtttc
     2821 tgaaggagct ctgtgaagtg cttgacggcg cctccggtct catgaagctt tgcccgcggt
     2881 acaattccca agaagaaact ttagagtttg tagcagatta cagtggacaa gataatttct
     2941 tacaacgagt gggacaaaat ggcttaaaga attcggagaa ggagtccact gtcaacagca
     3001 tctttcaggt catccggagc tgcaatcgaa gtctggagac agacgaggag gacagcccca
     3061 gtgaaggaaa cagctccagg aaaagctcct tgaaggataa aagccgatgg cagtttataa
     3121 ttggagattt gttggattca gacaatgaca tctttgagca atccaaagaa tacgactctc
     3181 atggttcaga ggactcacag aaggccttcg accatgggac ggagctcatc ccttggtacg
     3241 tgctgtccat ccaagccgat gtgcaccagt tcctgctgca gggggccacg gtcatccact
     3301 acgaccagga cacacacctc tctgcccgct gcttcctcca gcttcagccc gacaatagca
     3361 ccttgacctg ggtaaagccc acaactgcct ccccagccag cagtaaagca aaacttggtg
     3421 tacttaataa cacagctgag cctggaaaat tcccactact gggtaatgct ggattaagta
     3481 gcctgacgga aggggtcttg gatctttttg cagtgaaggc tgtatacatg ggccaccctg
     3541 gcattgatat acacactgtg tgtgttcaga acaaactggg tagcatgttc ctgtcagaga
     3601 ctggtgtgac attgctctat gggcttcaga ccacagacaa cagattattg cacttcgtgg
     3661 caccaaagca cacagctaaa atgctcttca gcggattatt ggaactcact agagctgtga
     3721 gaaagatgag gaaattccct gaccaaagac agcagtggct gcggaaacag tacgtcagcc
     3781 tttatcagga ggatggacgg tatgaaggcc caactttggc tcacgctgtg gagttgtttg
     3841 gtggcagacg gtggagtgct cgaaacccca gccccggaac atcagcaaag aatgctgaga
     3901 agcccaatat gcagagaaac aataccctgg gcataagcac taccaagaaa aagaagaaaa
     3961 tcctcatgag gggtgagagt ggagaggtaa ctgacgatga gatggcaacc cgaaaggcca
     4021 agatgcacaa agagtgtcga agccggagtg gttctgatcc tcaagacatt aatgaacaag
     4081 aagaatcaga ggtgaatgcc atcgctaacc ctccaaaccc cctcccttcc agaagagccc
     4141 actctttgac cacagctggg tcccccaact tggctgccgg gacgtcatct cccatcaggc
     4201 cagtgtcctc ccctgtgctg tcttcttcaa acaagagccc atccagtgct tggagcagta
     4261 gtagctggca cgggcggatc aaaggcggca tgaagggatt tcagagcttc atggtttcag
     4321 atagcaacat gagttttgtt gaatttgttg agctgttcaa atcattcagt gtcaggagcc
     4381 gcaaggacct gaaggatctg tttgatgtct atgcagtgcc ctgcaaccga tctggctccg
     4441 agtcagcccc actctacacc aacctgacaa ttgatgaaaa caccagcgat cttcagcctg
     4501 acctagatct gttgaccaga aatgtctcgg atttggggtt gttcattaag agtaaacagc
     4561 agctatcgga caaccagagg cagatatctg atgccattgc tgctgcaagc attgtgacaa
     4621 atggcactgg gattgagagc acatctctgg gcatttttgg ggtgggcata cttcagctca
     4681 acgatttcct cgtgaattgc caaggagaac actgcactta tgatgaaatc ctcagcatca
     4741 tccagaagtt cgagcctagc atcagtatgt gtcatcaggg actaatgtca tttgaagggt
     4801 ttgccaggtt tctgatggat aaagaaaatt ttgcctcaaa aaatgatgag tcacaggaga
     4861 acattaaaga actgcagcta cccctctcat actattacat cgaatcttcg cacaatacct
     4921 acctcacggg ccatcagctc aaaggagaat cctcggtaga actctacagc caggtccttt
     4981 tgcaaggctg tcgaagtgta gaattggact gctgggacgg agacgatggg atgcccatca
     5041 tttatcatgg acatacgctg acaaccaaga tccccttcaa ggaagtggtt gaagccattg
     5101 atcgcagtgc cttcatcaac tctgacctgc caatcatcat atcgattgag aaccactgtt
     5161 cattgcctca gcaacgaaaa atggcagaaa ttttcaagac tgtgtttgga gaaaagctgg
     5221 tgactaaatt cttatttgag actgatttct cagatgatcc aatgcttcct tcacctgacc
     5281 aactcagaaa gaaagttctt cttaaaaaca agaagctaaa agcccatcag acgccagtgg
     5341 atatcttaaa gcaaaaggct catcagttag catctatgca agtgcaggct tataatggtg
     5401 ggaatgccaa cccccgacct gccaataatg aggaagagga agatgaggag gacgaatatg
     5461 attatgacta tgaatccctt tctgatgaca acattctgga agacagacct gaaaataaat
     5521 catgtaatga caagcttcag tttgaatata atgaagaaat cccaaagagg ataaagaaag
     5581 cagataactc tgcttgcaac aaaggaaagg tttatgatat ggaactggga gaagaatttt
     5641 atcttgatca gaataaaaag gaaagcagac agattgcacc agagctttct gaccttgtaa
     5701 tctattgtca agcagtaaaa tttccaggac tgtcaactct aaatgcatct ggctctagca
     5761 gaggaaaaga aaggaaaagc aggaagtcca tttttggcaa caatccgggc agaatgagcc
     5821 caggggagac agcatcattt aacaaaacat ctggaaaaag ttcctgtgaa ggcattcgac
     5881 agacctggga ggaatcttct tcccctctca acccaaccac gtccctcagt gctatcatta
     5941 gaactcccaa atgttatcat atctcgtcgc tgaatgaaaa tgccgccaaa cgtctgtgtc
     6001 gcaggtattc tcagaaactg acccagcaca ccgcctgtca gctgctgaga acttaccctg
     6061 ctgccacccg catcgactct tccaacccga accccctcat gttctggctc catgggatac
     6121 agcttgtggc actcaactac cagactgatg atctcccttt acatttaaat gctgcaatgt
     6181 ttgaggcaaa tggtggttgt ggttatgtat tgaaacctcc agttctgtgg gacaagaact
     6241 gccccatgta tcagaagttt tctccactag aaagagatct ggacagcatg gatcctgcag
     6301 tctattcttt aactattgtc tctggtcaga atgtgtgccc cagtaatagc atgggaagcc
     6361 cgtgcattga agtcgacgtc ctgggcatgc ctctggacag ctgccatttc cgcacaaagc
     6421 ccatccatcg aaacaccctg aaccccatgt ggaacgagca gtttctgttc cacgttcact
     6481 tcgaagatct tgtatttctt cgttttgcag ttgtggaaaa caatagttca gcggtaactg
     6541 ctcagagaat cattccactg aaagctttaa aacgaggata tcgacatctt cagctgcgaa
     6601 accttcacaa tgaagtcttg gagatttcta gtttattcat taacagcaga aggatggaag
     6661 aaaattcctc tggcaatacc atgtcagcct cttcgatgtt taatacagaa gaaagaaaat
     6721 gtttgcagac tcacagagtc acggtgcatg gggtcccagg gccagagccc tttaccgttt
     6781 tcactattaa tggaggcacc aaggcaaagc agcttctgca gcaaattctg acaaatgaac
     6841 aagacatcaa acctgttacc acagactatt ttttgatgga agaaaaatat tttatatcta
     6901 aagaaaagaa tgaatgtagg aaacaaccat tccagagagc cattggtcca gaagaggaga
     6961 tcatgcaaat tttaagcagc tggtttccag aagagggata catgggcagg attgtcttaa
     7021 aaacccagca ggaaaaccta gaagagaaaa acattgttca agatgacaaa gaggtgatct
     7081 tgagctcaga ggaggagagt ttctttgtcc aagtgcatga tgtttctcca gagcaacctc
     7141 gaacagtcat caaagcaccc cgcgtcagca ctgcacagga tgtcattcag cagaccttat
     7201 gcaaagccaa atattcctac agcatcctga gcaaccccaa tccaagcgac tatgtgcttt
     7261 tggaagaggt ggtgaaagac actaccaaca agaagactac cacaccaaag tcctctcagc
     7321 gggtccttct ggatcaggag tgtgtgtttc aagcccaaag caagtggaaa ggtgcaggaa
     7381 aattcatcct taagctaaag gagcaggtgc aggcatctcg agaagataaa aagaaaggca
     7441 tttctttcgc aagtgaactc aagaagctca ccaagtcaac taaacagccc cgaggactta
     7501 catcaccttc tcagctcttg acctcagaaa gtatccaaac caaggaggag aaacctgtgg
     7561 gtggcttgtc ctccagtgac acaatggatt accgacagtg actaagggca gcatgtttaa
     7621 cccaggtgaa gatctttaag caagaagtta aagagtgaac atggtggaaa aaatataatt
     7681 attttcatca gacttaaact ggaaattgat gatttctgaa ctgaagcctt cacacatgtg
     7741 agatccatgc tgaggagaag caaaatggca cagggctagt tgccaccaac caatttactg
     7801 atgaatgaag cccaggggac tgccatttta taaatgtcag cagttggaaa aatcgtcacg
     7861 aattgactta gagcaagggt cagcaagctt gtctgtaaag ggccaaacag taaatatttt
     7921 agggctgggg gccataaaat atgttgcaac cacccaattc tgccattgta gtgcaaaagc
     7981 agccatagac aacacataca tgaacgaacg tggctgtatt ccaataaaac tttatttatg
     8041 gacactgaaa ttggaatttc atatattttt cacatgtcac aaatactctt gttttgactt
     8101 tttttcaacc atttaaaaac ttaaaaacta ttcttaattc aggggccata caaaaacagg
     8161 tggcaggcta gatttggccc aaggacctta atttgccaac acaactaaga gaagagaact
     8221 gggaacaagg agcacaaaga tctgaaaaca ggaaaggaag tttagccata cattttatgg
     8281 ccgagaatta gaagcttaga attagaagct ttggggcatt tcaagtgtaa atatgtccta
     8341 taacataaga gtcattaaaa ttcaatttag ttcctgtatt gtgtaccaca gtgcactcct
     8401 ctttaggatt tttttacata tagaaataat attgggtttt ttttaaggtt attgcctatt
     8461 cagttaatag ggttgcttta aaaaaggtta ttgcttaatc atagattaga ttactcattt
     8521 ttggttttca aaatgaattt agaatgacgt ataatttaat atctactgaa ttgcaatgtc
     8581 ttaacaagaa acctaacaat tttttaaagc aaaagtagat tgagttggcg tttaaattta
     8641 ttttgcaagg tttgtactga cactatactt atatatttat tatacatcgc tctcttgata
     8701 ttgccatgga ttagaagcat tagttctcag tacttgaaga caaacttcta aaaagaaaat
     8761 atatgctctg aacatctgaa atgggctaga ctttcaagta aaattgcttc atttctcatt
     8821 aactgaagag ctattgatcc aagtcatact tgccatttaa tgtaaattat ttttaaactt
     8881 tgctgtacaa aaccattaag tgtaaaggat tcttcatatt cttagtatga agcaaattat
     8941 gaattttaaa aatgaaatat gtattcctct aaaacccaaa cttttatctt tccattggta
     9001 tctttgaatt ttaagacact tttcttcaaa ttacaaaaca ctaaaactca ctcctaaact
     9061 tcactttgag aaactttttt aaccaattat aaaaataaaa ccatccccat gtgtttcttg
     9121 catattctaa aaacagaagt gttaaaaata caccacacag gctgggcaga gtggctcacg
     9181 cctgtaactc cagcactttg ggaggccaag atgggcggat caggacagag aatgaggcca
     9241 tcctggccaa catggtgaaa cccaatctct actaaaagta caaaaattag ctgagcgtgg
     9301 tggcacgtgc ctgtaatccc agctactcgg gaggctgagg caggagaatc acttgaacct
     9361 gggaggtgga ggctgcagtg agccaagatc gcaccaccac gctccagcct ggtgacagag
     9421 cgagactccg tctcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaac accatacagc
     9481 tttcatgtca ttgaaagttc ttactgggtc aaagccttaa ggctagaact accattttct
     9541 tgtcaacaga attcaggcta ttccagtttg atgtaatcta tacagtagta cagttttaag
     9601 tcaaatattc attctaacaa atgcacaatg ctgctccatt ttaaaaatat tccggaaaca
     9661 ctttatcaag cctctataag tgaacatgcc aaacagtttg ccctaccacg tgttgaaaac
     9721 tgagttgctg gtctaagtgg ctagaggcca aatgaaaact gtgcagagta acaagatgaa
     9781 aagactcgtc tctttaggtt tatcacattt gattctgatg ctaagcgctg ccccactcct
     9841 cctccatgac ctttaacaca ggtgtatgtt ttacaacata aatctgagac tgaagttgag
     9901 accaggttgt ttagcaagtg agagaatcca gcctactgcc taggttgcat cccaatttag
     9961 ttgtttatca cattttgagg tgaaagtaca tacttcattg tatttgagtc tttgggatta
    10021 cagaaagaac acattgtttc aaaatgtaaa gagttggctg ggcacagtgg ctcatgcctg
    10081 taatcccaac actctgggag gctgaggtgg gtggatcacc tgaggtctgg agttcgaggc
    10141 caacatggtg aaacccgtct ctactaaaaa tacaaaaatt agctgggtac taaaaataca
    10201 aaaattagtg gtggtgggca cctgtaaatc ccagctattg gggaggctga ggcaggagag
    10261 aattgcctga actcaagacg cagaggttgc agtgagtgga gactgtgcca ctgcactcca
    10321 gcctgggtac aagagtgaga ctccatctca aaaaaaaaaa aaaaaagtaa agagtctagt
    10381 ctactattat acacaaatgg ccagcacaat ctgatgttgg ctgaaaatat ttaagtttta
    10441 tttaaagctt tctgaattaa acagctatat tatgccaagt gaaagaaatt atcctaaata
    10501 gccactatga ctatacccat taccatttca cactttttag gccaccagaa atctgggtag
    10561 caaactcttc tcattaaagt tgatgtggac aagaatctaa atatgcaagt tggggtcatt
    10621 acaaaatttt aagaagcatc actgaaagtg aagagaaagg agcatgaatt ctgtcactct
    10681 attcagtgat gccaaatctg taggaatgat cctatctggg tagaaagtgc cctttgaggg
    10741 gtaaagcttc ttttcatgtc atcattagca agtaaaagtt atttacaaat tctccagttg
    10801 ggagtcaata tgaagtctag actcaacaaa agttgagtta caagtgactt gtttttaatc
    10861 aaacttgctt tcttttatgg gaggctttta tgcctcccat ctcaatacct ctggagacac
    10921 tggaagctca ttaatgaaag tgggccctct atgatatgta tcaatttacc ttttgctaac
    10981 tacatcgtcc ccttcctttc ttctctcctc ttccaatatc tctatagact tctgtcctct
    11041 gcccagagac ccacaggcct tgcttaattc tggaaagtta tcagggcttg cttactggcc
    11101 caataaaatt gaattaactc taaaacacaa aactccacat ctatgctccc atgctagtaa
    11161 agaagagtag gattttcctg gctggtgtct ttgatcttac attggcagcc tgcagggaaa
    11221 gtgctctcat ggtgaaagtc tctgacccct tttcagttgc ttatatatca gcagtgaggc
    11281 cagaaaagat atacctggga ccccaaaaaa gttagagaga aaagggagat tgtctcttat
    11341 acagagtcta gacttgggtc aatattcccc atgatccatt gttaataatt tatgtgttct
    11401 ctgccatcct tatgtagcag cttcctaaaa gcaatccttg gctgatggct atggattctg
    11461 acataggaat acctgaaatg agtccctttg aaacacatac tgagtctcta tgattaccaa
    11521 gttattcttt tttttttttt tttttttgag gcaaagtctc actctgttgc ccagcctgga
    11581 gtgcagtggt acgatctcga ctcaccacaa cctccacctc ccaggttcaa gtgattctcc
    11641 tgcctcagcc tcccaagtag ctgggactac aggtgtgcgc catgtccgtc taattttttt
    11701 tattttcagt agagacgggg gtttcactat gttggtaagg ctggtctcga actcctgacc
    11761 tcgtgatcca cccgcctcag cctcccaaag tgctgggatt acaggcgtga gccaccacac
    11821 ctggcctacc tactcttata catctcttag attcaaaaca tactatgcac aagcctgtca
    11881 ccaaacagat ctctgaaacc ttccctattg cagatgacat aggtctctaa acttttgaca
    11941 caagtaattc taacactgaa ttgggtactg tcgcattttt caaaagcgtt atgtggatga
    12001 tttgactcag catggaagac tgaggttgtc ttacacccat tatttcccac cccactctta
    12061 agtgccagca tagtgctaaa cacacagtag gtgctcatta tttgtctagt taaaaaacaa
    12121 attaaggctg tagcttaata tagcctcagg atatgtgtgt gcctgtgtgt gtgtgtgtgt
    12181 gtgtgtgtgt gtgtgtgtgt gtgtgtttaa acataagctt acatataagc gtatgtaagt
    12241 taatgcacaa atatatttcc tcaaattcac ataggatact caaatataga tgtataattt
    12301 tgtagtccca ctgtgattct ccatatgtat aacaagaaaa ttaaaggcat aatacagctg
    12361 tgaaatagct gatgagtttc tattttaagc tgatttttca ccagaagtat agtttctgct
    12421 gccaaagtaa agtataaatg tatttgtata tgtgtggaaa ataaataatt tgtgacatgt
    12481 a
//
