LOCUS       NM_015225              12612 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens prune homolog 2 with BCH domain (PRUNE2), transcript
            variant 1, mRNA.
ACCESSION   NM_015225 XM_041018
VERSION     NM_015225.3
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 12612)
  AUTHORS   Cardoso,M., Maia,S., Brandao,A., Sahasrabudhe,R., Lott,P.,
            Belter,N., Carvajal-Carmona,L.G., Paulo,P. and Teixeira,M.R.
  TITLE     Exome sequencing of affected duos and trios uncovers PRUNE2 as a
            novel prostate cancer predisposition gene
  JOURNAL   Br J Cancer 128 (6), 1077-1085 (2023)
   PUBMED   36564567
  REMARK    GeneRIF: Exome sequencing of affected duos and trios uncovers
            PRUNE2 as a novel prostate cancer predisposition gene.
REFERENCE   2  (bases 1 to 12612)
  AUTHORS   Li,T., Huang,S., Yan,W., Zhang,Y. and Guo,Q.
  TITLE     FOXF2 Regulates PRUNE2 Transcription in the Pathogenesis of
            Colorectal Cancer
  JOURNAL   Technol Cancer Res Treat 21, 15330338221118717 (2022)
   PUBMED   35929169
  REMARK    GeneRIF: FOXF2 Regulates PRUNE2 Transcription in the Pathogenesis
            of Colorectal Cancer.
REFERENCE   3  (bases 1 to 12612)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   4  (bases 1 to 12612)
  AUTHORS   Salameh,A., Lee,A.K., Cardo-Vila,M., Nunes,D.N., Efstathiou,E.,
            Staquicini,F.I., Dobroff,A.S., Marchio,S., Navone,N.M., Hosoya,H.,
            Lauer,R.C., Wen,S., Salmeron,C.C., Hoang,A., Newsham,I., Lima,L.A.,
            Carraro,D.M., Oliviero,S., Kolonin,M.G., Sidman,R.L., Do,K.A.,
            Troncoso,P., Logothetis,C.J., Brentani,R.R., Calin,G.A.,
            Cavenee,W.K., Dias-Neto,E., Pasqualini,R. and Arap,W.
  TITLE     PRUNE2 is a human prostate cancer suppressor regulated by the
            intronic long noncoding RNA PCA3
  JOURNAL   Proc Natl Acad Sci U S A 112 (27), 8403-8408 (2015)
   PUBMED   26080435
  REMARK    GeneRIF: Results show prostate cancer antigen 3 (PCA3) as a
            dominant-negative oncogene and PRUNE2 protein as an unrecognized
            tumor suppressor gene in prostate cancer.
REFERENCE   5  (bases 1 to 12612)
  AUTHORS   Harris,J.L., Richards,R.S., Chow,C.W., Lee,S., Kim,M., Buck,M.,
            Teng,L., Clarke,R., Gardiner,R.A. and Lavin,M.F.
  TITLE     BMCC1 is an AP-2 associated endosomal protein in prostate cancer
            cells
  JOURNAL   PLoS One 8 (9), e73880 (2013)
   PUBMED   24040105
  REMARK    GeneRIF: BMCC1 is an AP-2 associated endosomal protein in prostate
            cancer cells.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 12612)
  AUTHORS   Iwama,E., Tsuchimoto,D., Iyama,T., Sakumi,K., Nakagawara,A.,
            Takayama,K., Nakanishi,Y. and Nakabeppu,Y.
  TITLE     Cancer-related PRUNE2 protein is associated with nucleotides and is
            highly expressed in mature nerve tissues
  JOURNAL   J Mol Neurosci 44 (2), 103-114 (2011)
   PUBMED   21234814
  REMARK    GeneRIF: The nerve tissue-specific and post-development expression
            of PRUNE2/Prune2 suggests that PRUNE2 may contribute to the
            maintenance of mature nervous systems.
REFERENCE   7  (bases 1 to 12612)
  AUTHORS   Clarke,R.A., Zhao,Z., Guo,A.Y., Roper,K., Teng,L., Fang,Z.M.,
            Samaratunga,H., Lavin,M.F. and Gardiner,R.A.
  TITLE     New genomic structure for prostate cancer specific gene PCA3 within
            BMCC1: implications for prostate cancer detection and progression
  JOURNAL   PLoS One 4 (3), e4995 (2009)
   PUBMED   19319183
  REMARK    GeneRIF: the longer BMCC1-1 isoform is upregulated in PCa tissues
            and metastases
REFERENCE   8  (bases 1 to 12612)
  AUTHORS   Price,N.D., Trent,J., El-Naggar,A.K., Cogdell,D., Taylor,E.,
            Hunt,K.K., Pollock,R.E., Hood,L., Shmulevich,I. and Zhang,W.
  TITLE     Highly accurate two-gene classifier for differentiating
            gastrointestinal stromal tumors and leiomyosarcomas
  JOURNAL   Proc Natl Acad Sci U S A 104 (9), 3414-3419 (2007)
   PUBMED   17360660
  REMARK    GeneRIF: OBSCN and C9orf65 comprise a highly accurate two-gene
            classifier for differentiating gastrointestinal stromal tumors and
            leiomyosarcomas.
REFERENCE   9  (bases 1 to 12612)
  AUTHORS   Wang,A.G., Yoon,S.Y., Oh,J.H., Jeon,Y.J., Kim,M., Kim,J.M.,
            Byun,S.S., Yang,J.O., Kim,J.H., Kim,D.G., Yeom,Y.I., Yoo,H.S.,
            Kim,Y.S. and Kim,N.S.
  TITLE     Identification of intrahepatic cholangiocarcinoma related genes by
            comparison with normal liver tissues using expressed sequence tags
  JOURNAL   Biochem Biophys Res Commun 345 (3), 1022-1032 (2006)
   PUBMED   16712791
REFERENCE   10 (bases 1 to 12612)
  AUTHORS   Machida,T., Fujita,T., Ooo,M.L., Ohira,M., Isogai,E., Mihara,M.,
            Hirato,J., Tomotsune,D., Hirata,T., Fujimori,M., Adachi,W. and
            Nakagawara,A.
  TITLE     Increased expression of proapoptotic BMCC1, a novel gene with the
            BNIP2 and Cdc42GAP homology (BCH) domain, is associated with
            favorable prognosis in human neuroblastomas
  JOURNAL   Oncogene 25 (13), 1931-1942 (2006)
   PUBMED   16288218
  REMARK    GeneRIF: BMCC1 is a new member of prognostic factors for NBL and
            may play an important role in regulating differentiation, survival
            and aggressiveness of the tumor cells
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL390239.16, BC019095.2,
            DA410068.1, AB050197.1, AL359314.14 and BQ008420.1.
            
            On Nov 23, 2018 this sequence version replaced NM_015225.2.
            
            Summary: The protein encoded by this gene belongs to the B-cell
            CLL/lymphoma 2 and adenovirus E1B 19 kDa interacting family, whose
            members play roles in many cellular processes including apotosis,
            cell transformation, and synaptic function. Several functions for
            this protein have been demonstrated including suppression of Ras
            homolog family member A activity, which results in reduced stress
            fiber formation and suppression of oncogenic cellular
            transformation. A high molecular weight isoform of this protein has
            also been shown to colocalize with Adaptor protein complex 2,
            beta-Adaptin and endodermal markers, suggesting an involvement in
            post-endocytic trafficking. In prostate cancer cells, this gene
            acts as a tumor suppressor and its expression is regulated by
            prostate cancer antigen 3, a non-protein coding gene on the
            opposite DNA strand in an intron of this gene. Prostate cancer
            antigen 3 regulates levels of this gene through formation of a
            double-stranded RNA that undergoes adenosine deaminase actin on
            RNA-dependent adenosine-to-inosine RNA editing. Alternative
            splicing results in multiple transcript variants. [provided by
            RefSeq, Jul 2015].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. This RefSeq lacks full-length transcript
            support, but the extent of this transcript is supported by
            transcript alignments in human, aligning orthologous transcripts,
            and on functional support for the protein in PMID: 16288218.
            
            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##
            RNAseq introns :: mixed sample support SAMEA1965299, SAMEA1966682
                              [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            inferred exon combination :: based on alignments, homology
            MANE Ensembl match        :: ENST00000376718.8/ ENSP00000365908.3
            RefSeq Select criteria    :: based on conservation
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-27                AL390239.16        120672-120698       c
            28-904              BC019095.2         1-877
            905-963             DA410068.1         494-552
            964-5172            AB050197.1         58-4266
            5173-5174           AL359314.14        50215-50216         c
            5175-7681           AB050197.1         4269-6775
            7682-8360           AL359314.14        46368-47046         c
            8361-12611          AB050197.1         7440-11690
            12612-12612         BQ008420.1         18-18               c
FEATURES             Location/Qualifiers
     source          1..12612
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="9"
                     /map="9q21.2"
     gene            1..12612
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /note="prune homolog 2 with BCH domain"
                     /db_xref="GeneID:158471"
                     /db_xref="HGNC:HGNC:25209"
                     /db_xref="MIM:610691"
     exon            1..187
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     CDS             152..9418
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /note="isoform 1 is encoded by transcript variant 1; BCH
                     motif-containing molecule at the carboxyl terminal region
                     1; BNIP2 motif containing molecule at the carboxyl
                     terminal region 1; protein prune homolog 2; olfaxin; BNIP2
                     motif-containing molecule at the C-terminal region 1"
                     /codon_start=1
                     /product="protein prune homolog 2 isoform 1"
                     /protein_id="NP_056040.2"
                     /db_xref="CCDS:CCDS47982.1"
                     /db_xref="GeneID:158471"
                     /db_xref="HGNC:HGNC:25209"
                     /db_xref="MIM:610691"
                     /translation="MEEFLQRAKSKLNRSKRLEKVHVVIGPKSCDLDSLISTFTYAYF
                     LDKVSPPGVLCLPVLNIPRTEFNYFTETRFILEELNISESFHIFRDEINLHQLNDEGK
                     LSITLVGSSVLASEDKTLESAVVKVINPVEQSDANVEFRESSSSLVLKEILQEAPELI
                     TEQLAHRLRGSILFKWMTMESEKISEKQEEILSILEEKFPNLPPREDIINVLQETQFS
                     AQGLSIEQTMLKDLKELSDGEIKVAISTVSMNLENCLFHSNITSDLKAFTDKFGFDVL
                     ILFSSYLSEEQQPRRQIAVYSENMELCSQICCELEECQNPCLELEPFDCGCDEILVYQ
                     QEDPSVTCDQVVLVVKEVINRRCPEMVSNSRTSSTEAVAGSAPLSQGSSGIMELYGSD
                     IEPQPSSVNFIENPPDLNDSNQAQVDANVDLVSPDSGLATIRSSRSSKESSVFLSDDS
                     PVGEGAGPHHTLLPGLDSYSPIPEGAVAEEHAWSGEHGEHFDLFNFDPAPMASGQSQQ
                     SSHSADYSPADDFFPNSDLSEGQLPAGPEGLDGMGTNMSNYSSSSLLSGAGKDSLVEH
                     DEEFVQRQDSPRDNSERNLSLTDFVGDESPSPERLKNTGKRIPPTPMNSLVESSPSTE
                     EPASLYTEDMTQKATDTGHMGPPQTHARCSSWWGGLEIDSKNIADAWSSSEQESVFQS
                     PESWKEHKPSSIDRRASDSVFQPKSLEFTKSGPWESEFGQPELGSNDIQDKNEESLPF
                     QNLPMEKSPLPNTSPQGTNHLIEDFASLWHSGRSPTAMPEPWGNPTDDGEPAAVAPFP
                     AWSAFGKEDHDEALKNTWNLHPTSSKTPSVRDPNEWAMAKSGFAFSSSELLDNSPSEI
                     NNEAAPEIWGKKNNDSRDHIFAPGNPSSDLDHTWTNSKPPKEDQNGLVDPKTRGKVYE
                     KVDSWNLFEENMKKGGSDVLVPWEDSFLSYKCSDYSASNLGEDSVPSPLDTNYSTSDS
                     YTSPTFAGDEKETEHKPFAKEEGFESKDGNSTAEETDIPPQSLQQSSRNRISSGPGNL
                     DMWASPHTDNSSEINTTHNLDENELKTEHTDGKNISMEDDVGESSQSSYDDPSMMQLY
                     NETNRQLTLLHSSTNSRQTAPDSLDLWNRVILEDTQSTATISDMDNDLDWDDCSGGAA
                     IPSDGQTEGYMAEGSEPETRFTVRQLEPWGLEYQEANQVDWELPASDEHTKDSAPSEH
                     HTLNEKSGQLIANSIWDSVMRDKDMSSFMLPGSSHITDSEQRELPPEIPSHSANVKDT
                     HSPDAPAASGTSESEALISHLDKQDTERETLQSDAASLATRLENPGYFPHPDPWKGHG
                     DGQSESEKEAQGATDRGHLDEEEVIASGVENASGISEKGQSDQELSSLVASEHQEICI
                     KSGKISSLAVTFSPQTEEPEEVLEYEEGSYNLDSRDVQTGMSADNLQPKDTHEKHLMS
                     QRNSGETTETSDGMNFTKYVSVPEKDLEKTEECNFLEPENVGGGPPHRVPRSLDFGDV
                     PIDSDVHVSSTCSEITKNLDVKGSENSLPGAGSSGNFDRDTISSEYTHSSASSPELND
                     SSVALSSWGQQPSSGYQEENQGNWSEQNHQESELITTDGQVEIVTKVKDLEKNRINEF
                     EKSFDRKTPTFLEIWNDSVDGDSFSSLSSPETGKYSEHSGTHQESNLIASYQEKNEHD
                     ISATVQPEDARVISTSSGSDDDSVGGEESIEEEIQVANCHVAEDESRAWDSLNESNKF
                     LVTADPKSENIYDYLDSSEPAENENKSNPFCDNQQSSPDPWTFSPLTETEMQITAVEK
                     EKRSSPETGTTGDVAWQISPKASFPKNEDNSQLEMLGFSADSTEWWKASPQEGRLIES
                     PFERELSDSSGVLEINSSVHQNASPWGVPVQGDIEPVETHYTNPFSDNHQSPFLEGNG
                     KNSHEQLWNIQPRQPDPDADKFSQLVKLDQIKEKDSREQTFVSAAGDELTPETPTQEQ
                     CQDTMLPVCDHPDTAFTHAEENSCVTSNVSTNEGQETNQWEQEKSYLGEMTNSSIATE
                     NFPAVSSPTQLIMKPGSEWDGSTPSEDSRGTFVPDILHGNFQEGGQLASAAPDLWIDA
                     KKPFSLKADGENPDILTHCEHDSNSQASDSPDICHDSEAKQETEKHLSACMGPEVESS
                     ELCLTEPEIDEEPIYEPGREFVPSNAELDSENATVLPPIGYQADIKGSSQPASHKGSP
                     EPSEINGDNSTGLQVSEKGASPDMAPILEPVDRRIPRIENVATSIFVTHQEPTPEGDG
                     SWISDSFSPESQPGARALFDGDPHLSTENPALVPDALLASDTCLDISEAAFDHSFSDA
                     SGLNTSTGTIDDMSKLTLSEGHPETPVDGDLGKQDICSSEASWGDFEYDVMGQNIDED
                     LLREPEHFLYGGDPPLEEDSLKQSLAPYTPPFDLSYLTEPAQSAETIEEAGSPEDESL
                     GCRAAEIVLSALPDRRSEGNQAETKNRLPGSQLAVLHIREDPESVYLPVGAGSNILSP
                     SNVDWEVETDNSDLPAGGDIGPPNGASKEISELEEEKTIPTKEPEQIKSEYKEERCTE
                     KNEDRHALHMDYILVNREENSHSKPETCEERESIAELELYVGSKETGLQGTQLASFPD
                     TCQPASLNERKGLSAEKMSSKSDTRSSFESPAQDQSWMFLGHSEVGDPSLDARDSGPG
                     WSGKTVEPFSELGLGEGPQLQILEEMKPLESLALEEASGPVSQSQKSKSRGRAGPDAV
                     TLQAVTHDNEWEMLSPQPVQKNMIPDTEMEEETEFLELGTRISRPNGLLSEDVGMDIP
                     FEEGVLSPSAADMRPEPPNSLDLNDTHPRRIKLTAPNINLSLDQSEGSILSDDNLDSP
                     DEIDINVDELDTPDEADSFEYTGHDPTANKDSGQESESIPEYTAEEEREDNRLWRTVV
                     IGEQEQRIDMKVIEPYRRVISHGGYYGDGLNAIIVFAACFLPDSSRADYHYVMENLFL
                     YVISTLELMVAEDYMIVYLNGATPRRRMPGLGWMKKCYQMIDRRLRKNLKSFIIVHPS
                     WFIRTILAVTRPFISSKFSSKIKYVNSLSELSGLIPMDCIHIPESIIKLDEELREASE
                     AAKTSCLYNDPEMSSMEKDIDLKLKEKP"
     exon            188..292
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            293..495
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            496..659
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            660..812
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            813..907
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            908..1066
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            1067..7664
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            7665..8427
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            8428..8507
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            8508..8708
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            8709..8879
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            8880..8982
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            8983..9114
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            9115..9201
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            9202..9300
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            9301..9339
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            9340..9387
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     exon            9388..12612
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /inference="alignment:Splign:2.1.0"
     regulatory      12594..12599
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /note="hexamer: AATAAA"
     polyA_site      12612
                     /gene="PRUNE2"
                     /gene_synonym="BMCC1; BNIPXL; C9orf65; KIAA0367"
                     /note="major polyA site"
ORIGIN      
        1 ctccgccgca gccgcctcag agcggcagga gggagcagtc ggtcgctgcg ccccggcggg
       61 ccactttccc gggaccccgc tcgtcttcct tgggccgaga ttttccactg cgcccctccg
      121 agtacccggg ttccaaaccc ctagccacga catggaagaa tttttgcaac gcgccaaatc
      181 taaactgaat cgaagcaaac gcttggagaa ggtccatgtg gttattgggc ctaaatcgtg
      241 tgacttggat tctctcattt ctaccttcac atatgcttac tttctagaca aggtcagtcc
      301 accaggggtt ctgtgtttac cagtgctgaa cataccaaga actgaattca actacttcac
      361 cgagacgagg tttattttag aagagctaaa tatttccgaa tcattccaca tattccggga
      421 tgaaattaac ctgcatcagc taaatgatga agggaagtta tcgataacac ttgttggcag
      481 cagtgtgctg gcgagtgaag acaaaacttt agaatcagca gttgtcaaag tcattaatcc
      541 ggttgagcag agcgatgcca acgttgagtt ccgagagtct tcctcttctc tcgtgctaaa
      601 ggagattctc caagaggctc ctgagctcat caccgagcaa ctggctcatc gcctcagagg
      661 tagcattctt ttcaagtgga tgaccatgga atcagagaag atctcagaga agcaggagga
      721 aattctttct atcctggaag aaaaatttcc taacttgcct ccaagagagg acatcatcaa
      781 cgtcctacag gagacccagt tcagtgctca gggtttaagt attgaacaga caatgttgaa
      841 agatctaaag gagctgtcag atggagaaat aaaagtggcc attagtactg tgagcatgaa
      901 ccttgagaat tgtctatttc acagcaatat taccagtgac ttgaaagcat ttacagacaa
      961 gtttggtttt gatgtcctca tcctgttctc cagctatctg tcagaggagc agcagccgag
     1021 acgacagatt gctgtgtact cagaaaacat ggagctgtgc agtcagattt gctgtgagct
     1081 ggaagagtgt cagaaccctt gcctagaact ggagcccttt gactgtggct gtgatgagat
     1141 cctggtgtac caacaagagg acccttcagt gacttgtgat caggtggttc tcgttgtcaa
     1201 ggaagtcatc aacaggaggt gtccagagat ggtctccaat agccggacat cctcaacaga
     1261 agccgtggca ggcagtgccc ccctctccca ggggtcttct gggattatgg aattgtatgg
     1321 ttctgacata gagccacaac ccagctctgt gaatttcata gagaaccctc cagatctcaa
     1381 tgattctaac caggctcagg tggatgccaa tgtagacctt gttagcccag acagcggact
     1441 ggctaccatt aggagcagcc gctcatccaa ggagagctct gttttcctca gtgacgacag
     1501 ccccgtggga gaaggtgctg ggcctcacca cacccttctc ccagggcttg actcctacag
     1561 ccccatccct gaaggggcgg tggcggagga acatgcatgg tctggagaac acggtgagca
     1621 cttcgacctc ttcaattttg acccagcacc catggcttct gggcagtccc agcaatcttc
     1681 tcattctgca gactactccc cagcagatga cttcttcccc aacagtgacc tgtcagaagg
     1741 acagctcccc gctgggcctg aaggacttga tggcatggga accaacatgt ctaattattc
     1801 atccagttca cttttgtcag gggctggcaa agatagcctt gtggaacatg atgaggagtt
     1861 tgtccagaga caagacagtc ccagagataa ctctgaaaga aatttgagcc tgacagattt
     1921 tgtgggagat gaatcccctt ccccagaaag gctaaaaaat actggaaaga ggatcccacc
     1981 aacacccatg aatagtttag tagaaagctc gccatccact gaagaaccag cctcactcta
     2041 tacagaagat atgacccaaa aagcaactga cacaggtcac atggggccac ctcagaccca
     2101 tgcacggtgc agcagctggt ggggtggttt ggaaattgac tccaaaaata ttgcagatgc
     2161 gtggagttcc agtgaacagg aatctgtttt ccagagccct gaatcatgga aagagcataa
     2221 gccaagctcc attgatagga gagcctcaga ttctgtattt caaccaaaga gcctcgaatt
     2281 tacaaagtca ggtccctggg agtctgaatt tggtcagcct gaactgggta gcaatgatat
     2341 tcaagacaaa aatgaggaaa gcttgccgtt ccagaacctg cccatggaga agtcaccttt
     2401 gccaaataca tctccccaag gaacaaacca cctgatagaa gactttgctt ctttgtggca
     2461 ttctggtcgc tctcccacag ccatgcccga gccctgggga aatcctacag atgatggtga
     2521 accagcagct gtggcgccat tcccagcctg gagtgcattt ggtaaagaag atcatgatga
     2581 agctttaaaa aatacctgga atttgcaccc aacaagcagc aagacacctt ctgttaggga
     2641 cccgaatgag tgggccatgg caaaaagtgg gtttgccttt tcttcttcag aactactgga
     2701 caattcaccc agtgagataa acaatgaagc agctccagaa atctggggca agaaaaacaa
     2761 tgactccagg gatcacatct ttgcacctgg aaatcccagt tctgatctgg atcacacatg
     2821 gactaattct aagccaccaa aagaagatca gaatggttta gtggatccta aaactagggg
     2881 caaggtatat gaaaaggtag attcctggaa cctttttgag gagaatatga agaaaggagg
     2941 gtcagatgtc ctagttcctt gggaagattc cttcttatct tacaaatgtt ctgattacag
     3001 tgcatccaac ctaggagaag attcggtgcc ttccccctta gataccaatt attccacctc
     3061 agactcttac acatcaccaa catttgctgg agacgaaaag gaaactgaac acaagccatt
     3121 tgctaaagag gaaggttttg agtcaaaaga tggtaactcc acggcagagg agactgacat
     3181 tcctcctcag tcactgcaac agtcatctcg aaatcgaatc agttcaggtc ctgggaacct
     3241 agacatgtgg gcttcacctc atacagataa cagttctgaa ataaatacca ctcacaacct
     3301 ggatgaaaat gaactcaaga cagagcacac agatggtaag aatatctcca tggaggatga
     3361 cgtcggggaa agcagccagt ccagttacga cgaccccagc atgatgcaac tgtacaatga
     3421 aacaaaccga caactcacac ttttgcacag cagcaccaac tcccggcaga cggcccctga
     3481 cagtctcgac ttgtggaaca gagtgatttt ggaggatact cagtccactg caacgatctc
     3541 agatatggac aatgatttgg actgggatga ctgcagtggg ggtgcggcaa tccccagtga
     3601 tggtcaaaca gaaggataca tggctgaagg ttccgagccg gaaacccgat ttacagtgag
     3661 acagctggaa ccctggggct tggagtatca ggaagcaaat caggtagatt gggagctccc
     3721 tgcctctgat gagcatacca aggacagtgc tcccagtgaa catcacacat tgaatgagaa
     3781 aagtgggcag ctaattgcaa acagtatttg ggattctgtc atgagagata aagacatgtc
     3841 atcattcatg ttaccaggct cctcacatat cacagattca gagcaaaggg aattgcctcc
     3901 tgaaatcccc agccattcag caaatgttaa agacactcat tccccagatg cgccagcagc
     3961 ctctggaacc agtgaatcag aggcacttat atctcatctt gacaagcagg acacagagag
     4021 ggaaaccctg caaagtgatg cagcatcctt ggcgactagg cttgagaatc cagggtattt
     4081 tccacaccca gatccatgga aaggtcatgg cgatggacaa agtgaaagtg agaaggaagc
     4141 ccagggagcc actgacaggg ggcaccttga tgaagaggag gtgatcgcct ctggtgtgga
     4201 gaatgcctca gggatttctg aaaaagggca gagtgaccag gaactgtctt ctctggttgc
     4261 atctgaacat caggaaatct gcattaaatc aggcaaaatc agctctcttg ctgtcacttt
     4321 cagtcctcaa accgaggaac cagaggaagt tttagagtat gaggaggggt cttacaatct
     4381 agactcccgt gatgtgcaaa cagggatgtc cgcagataac ctgcagccaa aagataccca
     4441 tgaaaaacac ctcatgagtc aaagaaattc aggtgaaact actgagactt cagatgggat
     4501 gaatttcaca aaatatgtat ctgtacctga aaaggatctt gagaaaactg aagaatgtaa
     4561 ctttctagag ccagagaacg tgggtggagg gccacctcac agagttcccc gaagtcttga
     4621 ttttggggac gtccctatag acagtgatgt gcatgtcagc agcacatgtt ctgagataac
     4681 caaaaatctt gacgttaagg ggtctgaaaa tagccttcca ggagccggtt cgtctggaaa
     4741 ttttgacaga gatactattt ctagtgagta tactcattca agtgcatcaa gtcctgagtt
     4801 aaatgactct tcagttgcac tgtcctcctg gggccagcaa cccagttctg ggtatcaaga
     4861 agaaaaccaa ggcaactgga gtgaacagaa tcaccaagaa tctgaactaa ttaccactga
     4921 tggccaagta gaaatagtta ccaaagtgaa ggatttagag aaaaacagaa taaatgagtt
     4981 tgaaaagagc tttgatcgca aaactcctac atttttagag atctggaatg actcagttga
     5041 tggtgattcc ttttcctctt tatccagtcc tgaaacaggc aaatattctg aacattcagg
     5101 gacacatcag gaaagcaatc taattgctag ctaccaggag aaaaatgaac atgacatttc
     5161 tgcaactgtg cagccagagg atgccagggt catttcaaca agctcaggtt ctgatgatga
     5221 cagtgtcggt ggtgaagagt caatagagga agagatccag gtggccaact gccacgttgc
     5281 tgaggatgaa tccagagctt gggattcatt gaatgaatct aataagttct tggtcacagc
     5341 tgatcctaag tctgaaaata tttatgacta cctagacagc tcagagccag cagagaatga
     5401 gaataagtca aacccattct gtgacaatca acaaagcagc cctgatccct ggactttctc
     5461 accattaacg gagactgaaa tgcagattac agcagtggag aaggagaaga gatcttctcc
     5521 agaaacaggg acaacaggag atgttgcatg gcaaatatct cccaaagctt cgttcccaaa
     5581 gaacgaagat aattctcaac tggaaatgct gggcttctca gctgatagca ctgagtggtg
     5641 gaaggcctca ccccaggaag ggagactaat tgaaagtcca tttgaaaggg agctgtctga
     5701 ctccagtggt gtgttggaga taaattcttc agtacaccaa aatgccagtc cctggggagt
     5761 accagttcag ggtgatattg agcccgtgga aacacactat actaatcctt ttagtgacaa
     5821 ccatcagtca ccctttctgg aaggtaatgg gaagaactcc catgagcaac tctggaacat
     5881 tcaaccaagg cagccagacc cagatgctga caagttcagc cagcttgtaa aattagacca
     5941 aattaaagaa aaggactcaa gagagcaaac ctttgtgtct gctgctggtg atgagctgac
     6001 tcctgaaaca cctacccaag agcagtgtca ggacaccatg ctgccagtct gtgatcatcc
     6061 ggacacagcc tttactcacg cagaggaaaa tagttgtgtt acatctaatg tttcaactaa
     6121 tgaaggtcaa gaaacaaatc agtgggaaca agaaaaatca tacctaggtg agatgacaaa
     6181 ttcaagcatt gccacagaaa attttcctgc tgtcagttct cccacccaac tgataatgaa
     6241 gccaggctct gaatgggatg gctctacccc aagtgaggac tcccgaggta cctttgtgcc
     6301 agatatttta catggcaact ttcaagaggg tgggcagctg gcctctgccg cgcctgactt
     6361 gtggatagat gctaagaagc ccttcagttt gaaagcagat ggtgagaatc ctgatatcct
     6421 gacgcactgc gaacatgaca gcaattctca ggcttccgac agccctgata tatgtcacga
     6481 ttctgaagca aagcaagaga ctgagaagca cctcagtgct tgcatgggac ctgaagtgga
     6541 atccagtgag ctttgtctca ctgagccaga gatagatgaa gaacccattt atgagcctgg
     6601 acgggagttt gtcccatcca atgcagaact cgattctgaa aacgcaactg tgctgcctcc
     6661 aattggctat caagcagaca taaagggctc ctctcagccc gcctctcata aaggttcacc
     6721 tgaaccttct gaaataaacg gtgacaacag tacaggttta caagtatcag aaaaaggagc
     6781 cagcccagat atggcaccaa ttttggaacc agttgacaga agaatcccaa ggattgaaaa
     6841 tgtggcaact agcatttttg taactcacca agagccaact ccagaaggtg acggttcttg
     6901 gatatcagac agcttttctc ctgaaagtca gcctggtgca agagctttgt ttgatggtga
     6961 tccacattta tccacagaga atcctgcctt ggttcctgat gctttgctag cctcagacac
     7021 ttgtctggat ataagcgaag ctgcctttga ccacagtttc agcgatgcct caggtctcaa
     7081 cacatccacg ggaacaatag atgacatgag taaactgaca ttatccgaag gccatccgga
     7141 aacgccagtt gatggggacc tagggaagca agatatctgc tcatctgaag cctcgtgggg
     7201 tgattttgaa tatgatgtaa tgggccagaa tatcgatgaa gatttactga gagagcctga
     7261 acacttcctg tatggtggtg accctccttt ggaggaagat tctctgaagc agtcgctggc
     7321 accgtacaca cctccctttg atttgtctta tctcacagaa cctgcccaga gtgctgaaac
     7381 aatagaggaa gctgggtctc cagaggatga atctctggga tgcagagcag cagagatagt
     7441 gctttctgca cttcctgatc gaagaagtga gggaaaccag gctgagacca aaaacagact
     7501 gcctggatcc cagctggctg tgctgcatat tcgtgaagac cctgagtccg tttatttgcc
     7561 ggtaggagca ggctccaaca ttttgtctcc atcaaacgtt gactgggaag tagaaacaga
     7621 taattctgat ttaccagcag gtggagacat aggaccacca aatggtgcca gcaaggaaat
     7681 atcagaattg gaagaagaaa aaacaattcc taccaaagag cctgagcaga taaaatcaga
     7741 atacaaggaa gaaagatgta cagagaagaa tgaagatcgt catgcactac acatggatta
     7801 catacttgta aaccgtgaag aaaattcaca ctcaaagcca gagacctgtg aagaaagaga
     7861 aagcatagct gaattagaat tgtatgtagg ttccaaagaa acagggctgc agggaactca
     7921 gttagcaagc ttcccagaca catgtcagcc agcctcctta aatgaaagaa aaggtctctc
     7981 tgcagagaaa atgtcttcta aaagcgatac gagatcatct tttgaaagcc ctgcacaaga
     8041 ccagagttgg atgttcttgg gccatagtga ggttggtgat ccatcactgg atgccaggga
     8101 ctcagggcct gggtggtctg gcaagactgt ggagccgttc tctgaactcg gcttgggtga
     8161 gggtccccag ctgcagattc tggaagaaat gaagcctcta gaatctttgg cactagagga
     8221 agcctctggt ccagtcagcc aatcacagaa gagtaagagc cgaggcaggg ctggcccgga
     8281 tgcagttacg ttgcaggctg tcacccatga caatgaatgg gaaatgcttt caccacagcc
     8341 tgttcagaaa aacatgatcc ctgacacgga aatggaggag gagacagagt tccttgagct
     8401 cggaaccagg atatcaagac caaatggact actgtcagag gatgtaggaa tggacatccc
     8461 ctttgaagag ggcgtgctga gtcccagtgc tgcagacatg aggcctgaac ctcctaattc
     8521 tctggatctt aatgacactc atcctcggag aatcaagctc acagccccaa atatcaatct
     8581 ttctctggac caaagtgaag gatctattct ctctgatgat aacttggaca gtccagatga
     8641 aattgacatc aatgtggatg aacttgatac ccccgatgaa gcagattctt ttgagtacac
     8701 tggccatgat cccacagcca acaaagattc tggccaagag tcagagtcta ttccagaata
     8761 tacggccgaa gaggaacggg aggacaaccg gctttggagg acagtggtca ttggagaaca
     8821 agagcagcgc attgacatga aggtcatcga gccctacagg agagtcattt ctcacggagg
     8881 atactatggg gacggtctaa atgccatcat tgtgtttgcc gcctgttttc tgccagacag
     8941 cagtcgggcg gattaccact atgtcatgga aaatcttttc ctatatgtaa taagtacttt
     9001 agagttgatg gtagctgaag actatatgat tgtgtacttg aatggtgcaa ccccaagaag
     9061 gaggatgcca gggctaggct ggatgaagaa atgctaccag atgattgaca gacggttgag
     9121 gaagaatttg aaatcattca tcattgttca tccatcttgg ttcatcagaa caatccttgc
     9181 tgtgacacga ccttttataa gttcaaaatt cagcagtaaa attaaatatg tcaatagctt
     9241 atcagaactc agtgggctga tcccaatgga ttgcatccac attccagaga gcatcatcaa
     9301 actggatgaa gaactgaggg aagcatcaga ggcagctaaa actagctgcc tttacaatga
     9361 tccagaaatg tcttctatgg agaaggatat tgacttgaag ctgaaagaaa agccttagtt
     9421 ggccatgctg gaagaagagg atgcttttct ggttcatggt tctgttgaaa catatctacc
     9481 tgaaagagac agggctgatg ttaccttttt ccactttgca ctacctggtg ccattctaaa
     9541 tttctaaggg gaaaaataga aagtttgttt actcttaaga tattttatga aattgtgtgt
     9601 actttcctat tttgccaatt atgtgcctca aagattttag ttgagcctta gcaagaaagt
     9661 aggaccttcc atttcaatac ttcattaaca cggtgtagtg atactttgtc ccttagactg
     9721 gtgtttacca gtaagatacc tttaatccac tgttaagtat gagtggattt gtttccatag
     9781 attagctgga tttccttttg gtgattgcat taggtttaaa gtacacaggt ctcaactctc
     9841 cccaggaaag tttcccctgt ttgactccac ctttaaaatc ctaagcctga ctaggacagc
     9901 cacaaaccac acaaggtgta aaaccatcat cagctaagtg cccgttttgt tcttgtttac
     9961 cagaatctcc tttaacttct caaagggaag ccgggctttc taatccacgt caactttatt
    10021 ttagttgtca aattgggcat tatattttat gtaaattggt cttttaacat cattttcctg
    10081 atgaatgttg gtgaccacca cattgtgaaa tttaagaatc cgtgttgcat gtttggtagc
    10141 tctctgagtt tcaggccata aactcagctc cagaggttac cttttaagtg ccaagaactc
    10201 aagtgcaagg tggcctactc aaaaatcatt tggtagcatt cagttattca tgaattcctc
    10261 tctcgcatgc attataaaaa gtgatctgct ttaaaacacc gtaatctgat cataggctta
    10321 aaattaaata tgagtattac tttcatgtac aaaatatttc ctttatagtc ttcatatgcc
    10381 ctttaaaatg ccaacaagat ttcaagtctg taggcctcta gtgaggtggg gtggcaaacc
    10441 acagctaagt ctcgctcacc actgcaagct aagaatggtt tttacatttt gggttggaaa
    10501 aatttttttt gaatatttca tgacacatga aaattattca aatgttagtg ccgataaata
    10561 aagtggtact gaaacacagc cacacaaact tgtttttgta ctgtctacag ctactttcac
    10621 actacagccg cagagctgag cagttcagca gaccgtatgt cccacaatgc ctaaaacatt
    10681 gactatgttt acagaaaaag tttgctgacc cctgctctag caaacgcatc ctttcctact
    10741 ccaccccaat ttgtatttag atagtttctc taacagaacg gacaaatgag gctgcaaact
    10801 aatttatttt tgtcaaaaat caatgttttg acatccacag acagtgaaat aaaagaaatg
    10861 gcttgctgaa aaacatgagg agtcctagcc acaaaatcac tgcttaggtt gcaattgcca
    10921 aaatgaagcc ttcttagaag cacttcttta gtatatacag gtgttggctg aagtccgtgc
    10981 ctcactctgg gaaccattct tagtctccag tgtctcctat tacaaagaag ctggcagaaa
    11041 taaaaatgaa ggggtgagag cggttccacc ctagtctcat ggtggaaaat tcattgggga
    11101 gagctgtcca ggatatttgg agtcctgggt agaaggagct tgtaactact ttaaagtcga
    11161 catctttgca caggtgattg agtttctctg acctcattgc ttcacctctg tctcctcccg
    11221 tccttccgca cgtgcccaca cacacgcagt tcagccctct ttcctccata agcctccatc
    11281 gttttctctt ttctcctctt gatcctttca agcgagtatc ttgttgaatt gtatgttctg
    11341 ttggatctcc tccttcataa catctggctt gttggacaga aaaaccctac agcccacccc
    11401 ctcccacagc ccacctccac ttttgaaagc ccaaattaca cctctcccag aacacagtgt
    11461 tgacgtaaat acagttaccc aatattcctg tttgttcacc tatttgctac tttcactcag
    11521 tagcatccca ttttgtaaaa tgaattccat ggtcaccctg tcacaggaag taatgaaaaa
    11581 tccagtgttc agtgtagtgg tgcaaacctg agggcataga gctgttcata gagggctctt
    11641 gttatagcca aacagacaca gcaacaatct caccatttat atatatattt ttaacttgtc
    11701 cagctcatct atggaaaact actcaggtgg tatgctgttt gaagcctcat cttcctacat
    11761 gaaaattatg ggcatttgtc ccaatgattt tgtttcagct gttctgtagg ctgcataacc
    11821 actctgatat ttaggtatct gctattttat tatcttaaaa gacaaattaa tttaattgca
    11881 tgtgctaggg aaaagctacc atgtacattc accccaagta aatagaatcc tagatgaatc
    11941 ctagaaaaat aatccctaag cagataggta gacagaggta aacattcaca tgatttagct
    12001 ctctagctct tgcactctga acattcttgc tttggttctg acttctggga actgctttgc
    12061 atttctccta tagatctgta gttaagggaa ccaaggggtc attggggcaa aagcattgtt
    12121 tctcaaagct ccttgattaa gagaaagaac agaaatttgc acagaagata gtgtcaagga
    12181 gtgagaaagt ttgtttgagg gcagtagctc agtgtggaag aaaatcctga agtttctgtt
    12241 gaagccatac aatgttctat ggggttactc tctaagacat tctctgaggt gtgtgaggaa
    12301 gtcactactc ctagcctttg ttaagatgta attttaaata ttcagttatg gtactatgtt
    12361 tgcaactctc gtcttatcac aatgcctcag tagtttgttc ccttagaaac atttagatgt
    12421 gcacaaatta atcttttata tatctaaagg tttttctatc atgcattgga ttgctcagaa
    12481 taaagtgtct gttagacttc gttttggtaa ataaattctc cataatgtag attaataata
    12541 taaaagtctt taatgacaca atatatctat atagcctcac tgtataattc agaaataaaa
    12601 attgattctg ca
//
