LOCUS       NM_015001              12385 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens spen family transcriptional repressor (SPEN), mRNA.
ACCESSION   NM_015001
VERSION     NM_015001.3
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 12385)
  AUTHORS   Button,A.C., Hall,S.D., Ashley,E.L. and McHugh,C.A.
  TITLE     Dissection of protein and RNA regions required for SPEN binding to
            XIST A-repeat RNA
  JOURNAL   RNA 30 (3), 240-255 (2024)
   PUBMED   38164599
  REMARK    GeneRIF: Dissection of protein and RNA regions required for SPEN
            binding to XIST A-repeat RNA.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 12385)
  AUTHORS   Benz,C., Ali,M., Krystkowiak,I., Simonetti,L., Sayadi,A.,
            Mihalic,F., Kliche,J., Andersson,E., Jemth,P., Davey,N.E. and
            Ivarsson,Y.
  TITLE     Proteome-scale mapping of binding sites in the unstructured regions
            of the human proteome
  JOURNAL   Mol Syst Biol 18 (1), e10584 (2022)
   PUBMED   35044719
REFERENCE   3  (bases 1 to 12385)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   4  (bases 1 to 12385)
  AUTHORS   Radio,F.C., Pang,K., Ciolfi,A., Levy,M.A., Hernandez-Garcia,A.,
            Pedace,L., Pantaleoni,F., Liu,Z., de Boer,E., Jackson,A.,
            Bruselles,A., McConkey,H., Stellacci,E., Lo Cicero,S., Motta,M.,
            Carrozzo,R., Dentici,M.L., McWalter,K., Desai,M., Monaghan,K.G.,
            Telegrafi,A., Philippe,C., Vitobello,A., Au,M., Grand,K.,
            Sanchez-Lara,P.A., Baez,J., Lindstrom,K., Kulch,P., Sebastian,J.,
            Madan-Khetarpal,S., Roadhouse,C., MacKenzie,J.J., Monteleone,B.,
            Saunders,C.J., Jean Cuevas,J.K., Cross,L., Zhou,D., Hartley,T.,
            Sawyer,S.L., Monteiro,F.P., Secches,T.V., Kok,F.,
            Schultz-Rogers,L.E., Macke,E.L., Morava,E., Klee,E.W.,
            Kemppainen,J., Iascone,M., Selicorni,A., Tenconi,R., Amor,D.J.,
            Pais,L., Gallacher,L., Turnpenny,P.D., Stals,K., Ellard,S.,
            Cabet,S., Lesca,G., Pascal,J., Steindl,K., Ravid,S., Weiss,K.,
            Castle,A.M.R., Carter,M.T., Kalsner,L., de Vries,B.B.A., van
            Bon,B.W., Wevers,M.R., Pfundt,R., Stegmann,A.P.A., Kerr,B.,
            Kingston,H.M., Chandler,K.E., Sheehan,W., Elias,A.F., Shinde,D.N.,
            Towne,M.C., Robin,N.H., Goodloe,D., Vanderver,A., Sherbini,O.,
            Bluske,K., Hagelstrom,R.T., Zanus,C., Faletra,F., Musante,L.,
            Kurtz-Nelson,E.C., Earl,R.K., Anderlid,B.M., Morin,G., van
            Slegtenhorst,M., Diderich,K.E.M., Brooks,A.S., Gribnau,J.,
            Boers,R.G., Finestra,T.R., Carter,L.B., Rauch,A., Gasparini,P.,
            Boycott,K.M., Barakat,T.S., Graham,J.M. Jr., Faivre,L., Banka,S.,
            Wang,T., Eichler,E.E., Priolo,M., Dallapiccola,B.,
            Vissers,L.E.L.M., Sadikovic,B., Scott,D.A., Holder,J.L. Jr. and
            Tartaglia,M.
  TITLE     SPEN haploinsufficiency causes a neurodevelopmental disorder
            overlapping proximal 1p36 deletion syndrome with an episignature of
            X chromosomes in females
  JOURNAL   Am J Hum Genet 108 (3), 502-516 (2021)
   PUBMED   33596411
  REMARK    GeneRIF: SPEN haploinsufficiency causes a neurodevelopmental
            disorder overlapping proximal 1p36 deletion syndrome with an
            episignature of X chromosomes in females.
REFERENCE   5  (bases 1 to 12385)
  AUTHORS   Li,Y., Lv,Y., Cheng,C., Huang,Y., Yang,L., He,J., Tao,X., Hu,Y.,
            Ma,Y., Su,Y., Wu,L., Yu,G., Jiang,Q., Liu,S., Liu,X. and Liu,Z.
  TITLE     SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal
            carcinoma
  JOURNAL   Cell Death Dis 11 (7), 509 (2020)
   PUBMED   32641685
  REMARK    GeneRIF: SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal
            carcinoma.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 12385)
  AUTHORS   Oswald,F., Kostezka,U., Astrahantseff,K., Bourteele,S.,
            Dillinger,K., Zechner,U., Ludwig,L., Wilda,M., Hameister,H.,
            Knochel,W., Liptay,S. and Schmid,R.M.
  TITLE     SHARP is a novel component of the Notch/RBP-Jkappa signalling
            pathway
  JOURNAL   EMBO J 21 (20), 5417-5426 (2002)
   PUBMED   12374742
  REMARK    GeneRIF: SHARP is a novel component of the HDAC corepressor
            complex, recruited by RBP-Jkappa to repress transcription of target
            genes in the absence of activated Notch.
REFERENCE   7  (bases 1 to 12385)
  AUTHORS   Shi,Y., Hon,M. and Evans,R.M.
  TITLE     The peroxisome proliferator-activated receptor delta, an integrator
            of transcriptional repression and nuclear receptor signaling
  JOURNAL   Proc Natl Acad Sci U S A 99 (5), 2613-2618 (2002)
   PUBMED   11867749
REFERENCE   8  (bases 1 to 12385)
  AUTHORS   Shi,Y., Downes,M., Xie,W., Kao,H.Y., Ordentlich,P., Tsai,C.C.,
            Hon,M. and Evans,R.M.
  TITLE     Sharp, an inducible cofactor that integrates nuclear receptor
            repression and activation
  JOURNAL   Genes Dev 15 (9), 1140-1151 (2001)
   PUBMED   11331609
REFERENCE   9  (bases 1 to 12385)
  AUTHORS   Newberry,E.P., Latifi,T. and Towler,D.A.
  TITLE     The RRM domain of MINT, a novel Msx2 binding protein, recognizes
            and regulates the rat osteocalcin promoter
  JOURNAL   Biochemistry 38 (33), 10678-10690 (1999)
   PUBMED   10451362
REFERENCE   10 (bases 1 to 12385)
  AUTHORS   Ternovskaia,L.N., Prokhorova,L.G. and Moroz,V.M.
  TITLE     [Antagonistic interrelationships between the staphylococci and
            Sarcina isolated from the upper respiratory tracts of virtually
            healthy persons]
  JOURNAL   Antibiotiki 21 (12), 1072-1075 (1976)
   PUBMED   1020939
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL450998.19, AF356524.1 and
            AL034555.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_015001.2.
            
            Summary: This gene encodes a hormone inducible transcriptional
            repressor. Repression of transcription by this gene product can
            occur through interactions with other repressors, by the
            recruitment of proteins involved in histone deacetylation, or
            through sequestration of transcriptional activators. The product of
            this gene contains a carboxy-terminal domain that permits binding
            to other corepressor proteins. This domain also permits interaction
            with members of the NuRD complex, a nucleosome remodeling protein
            complex that contains deacetylase activity. In addition, this
            repressor contains several RNA recognition motifs that confer
            binding to a steroid receptor RNA coactivator; this binding can
            modulate the activity of both liganded and nonliganded steroid
            receptors. [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 :: AF356524.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000375759.8/ ENSP00000364912.3
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-157               AL450998.19        124943-125099
            158-12384           AF356524.1         1-12227
            12385-12385         AL034555.2         56583-56583
FEATURES             Location/Qualifiers
     source          1..12385
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p36.21-p36.13"
     gene            1..12385
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /note="spen family transcriptional repressor"
                     /db_xref="GeneID:23013"
                     /db_xref="HGNC:HGNC:17575"
                     /db_xref="MIM:613484"
     exon            1..444
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     CDS             362..11356
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /note="Msx2 interacting nuclear target (MINT) homolog;
                     nuclear receptor transcription cofactor;
                     SMART/HDAC1-associated repressor protein; spen homolog,
                     transcriptional regulator"
                     /codon_start=1
                     /product="msx2-interacting protein"
                     /protein_id="NP_055816.2"
                     /db_xref="CCDS:CCDS164.1"
                     /db_xref="GeneID:23013"
                     /db_xref="HGNC:HGNC:17575"
                     /db_xref="MIM:613484"
                     /translation="MVRETRHLWVGNLPENVREEKIIEHFKRYGRVESVKILPKRGSE
                     GGVAAFVDFVDIKSAQKAHNSVNKMGDRDLRTDYNEPGTIPSAARGLDDTVSIASRSR
                     EVSGFRGGGGGPAYGPPPSLHAREGRYERRLDGASDNRERAYEHSAYGHHERGTGGFD
                     RTRHYDQDYYRDPRERTLQHGLYYASRSRSPNRFDAHDPRYEPRAREQFTLPSVVHRD
                     IYRDDITREVRGRRPERNYQHSRSRSPHSSQSRNQSPQRLASQASRPTRSPSGSGSRS
                     RSSSSDSISSSSSTSSDSSDSSSSSSDDSPARSVQSAAVPAPTSQLLSSLEKDEPRKS
                     FGIKVQNLPVRSTDTSLKDGLFHEFKKFGKVTSVQIHGTSEERYGLVFFRQQEDQEKA
                     LTASKGKLFFGMQIEVTAWIGPETESENEFRPLDERIDEFHPKATRTLFIGNLEKTTT
                     YHDLRNIFQRFGEIVDIDIKKVNGVPQYAFLQYCDIASVCKAIKKMDGEYLGNNRLKL
                     GFGKSMPTNCVWLDGLSSNVSDQYLTRHFCRYGPVVKVVFDRLKGMALVLYNEIEYAQ
                     AAVKETKGRKIGGNKIKVDFANRESQLAFYHCMEKSGQDIRDFYEMLAERREERRASY
                     DYNQDRTYYESVRTPGTYPEDSRRDYPARGREFYSEWETYQGDYYESRYYDDPREYRD
                     YRNDPYEQDIREYSYRQRERERERERFESDRDRDHERRPIERSQSPVHLRRPQSPGAS
                     PSQAERLPSDSERRLYSRSSDRSGSCSSLSPPRYEKLDKSRLERYTKNEKTDKERTFD
                     PERVERERRLIRKEKVEKDKTDKQKRKGKVHSPSSQSSETDQENEREQSPEKPRSCNK
                     LSREKADKEGIAKNRLELMPCVVLTRVKEKEGKVIDHTPVEKLKAKLDNDTVKSSALD
                     QKLQVSQTEPAKSDLSKLESVRMKVPKEKGLSSHVEVVEKEGRLKARKHLKPEQPADG
                     VSAVDLEKLEARKRRFADSNLKAEKQKPEVKKSSPEMEDARVLSKKQPDVSSREVILL
                     REGEAERKPVRKEILKRESKKIKLDRLNTVASPKDCQELASISVGSGSRPSSDLQARL
                     GELAGESVENQEVQSKKPIPSKPQLKQLQVLDDQGPEREDVRKNYCSLRDETPERKSG
                     QEKSHSVNTEEKIGIDIDHTQSYRKQMEQSRRKQQMEMEIAKSEKFGSPKKDVDEYER
                     RSLVHEVGKPPQDVTDDSPPSKKKRMDHVDFDICTKRERNYRSSRQISEDSERTGGSP
                     SVRHGSFHEDEDPIGSPRLLSVKGSPKVDEKVLPYSNITVREESLKFNPYDSSRREQM
                     ADMAKIKLSVLNSEDELNRWDSQMKQDAGRFDVSFPNSIIKRDSLRKRSVRDLEPGEV
                     PSDSDEDGEHKSHSPRASALYESSRLSFLLRDREDKLRERDERLSSSLERNKFYSFAL
                     DKTITPDTKALLERAKSLSSSREENWSFLDWDSRFANFRNNKDKEKVDSAPRPIPSWY
                     MKKKKIRTDSEGKMDDKKEDHKEEEQERQELFASRFLHSSIFEQDSKRLQHLERKEED
                     SDFISGRIYGKQTSEGANSTTDSIQEPVVLFHSRFMELTRMQQKEKEKDQKPKEVEKQ
                     EDTENHPKTPESAPENKDSELKTPPSVGPPSVTVVTLESAPSALEKTTGDKTVEAPLV
                     TEEKTVEPATVSEEAKPASEPAPAPVEQLEQVDLPPGADPDKEAAMMPAGVEEGSSGD
                     QPPYLDAKPPTPGASFSQAESNVDPEPDSTQPLSKPAQKSEEANEPKAEKPDATADAE
                     PDANQKAEAAPESQPPASEDLEVDPPVAAKDKKPNKSKRSKTPVQAAAVSIVEKPVTR
                     KSERIDREKLKRSNSPRGEAQKLLELKMEAEKITRTASKNSAADLEHPEPSLPLSRTR
                     RRNVRSVYATMGDHENRSPVKEPVEQPRVTRKRLERELQEAAAVPTTPRRGRPPKTRR
                     RADEEEENEAKEPAETLKPPEGWRSPRSQKTAAGGGPQGKKGKNEPKVDATRPEATTE
                     VGPQIGVKESSMEPKAAEEEAGSEQKRDRKDAGTDKNPPETAPVEVVEKKPAPEKNSK
                     SKRGRSRNSRLAVDKSASLKNVDAAVSPRGAAAQAGERESGVVAVSPEKSESPQKEDG
                     LSSQLKSDPVDPDKEPEKEDVSASGPSPEATQLAKQMELEQAVEHIAKLAEASASAAY
                     KADAPEGLAPEDRDKPAHQASETELAAAIGSIINDISGEPENFPAPPPYPGESQTDLQ
                     PPAGAQALQPSEEGMETDEAVSGILETEAATESSRPPVNAPDPSAGPTDTKEARGNSS
                     ETSHSVPEAKGSKEVEVTLVRKDKGRQKTTRSRRKRNTNKKVVAPVESHVPESNQAQG
                     ESPAANEGTTVQHPEAPQEEKQSEKPHSTPPQSCTSDLSKIPSTENSSQEISVEERTP
                     TKASVPPDLPPPPQPAPVDEEPQARFRVHSIIESDPVTPPSDPSIPIPTLPSVTAAKL
                     SPPVASGGIPHQSPPTKVTEWITRQEEPRAQSTPSPALPPDTKASDVDTSSSTLRKIL
                     MDPKYVSATSVTSTSVTTAIAEPVSAAPCLHEAPPPPVDSKKPLEEKTAPPVTNNSEI
                     QASEVLVAADKEKVAPVIAPKITSVISRMPVSIDLENSQKITLAKPAPQTLTGLVSAL
                     TGLVNVSLVPVNALKGPVKGSVTTLKSLVSTPAGPVNVLKGPVNVLTGPVNVLTTPVN
                     ATVGTVNAAPGTVNAAASAVNATASAVTVTAGAVTAASGGVTATTGTVTMAGAVIAPS
                     TKCKQRASANENSRFHPGSMPVIDDRPADAGSGAGLRVNTSEGVVLLSYSGQKTEGPQ
                     RISAKISQIPPASAMDIEFQQSVSKSQVKPDSVTASQPPSKGPQAPAGYANVATHSTL
                     VLTAQTYNASPVISSVKADRPSLEKPEPIHLSVSTPVTQGGTVKVLTQGINTPPVLVH
                     NQLVLTPSIVTTNKKLADPVTLKIETKVLQPANLGSTLTPHHPPALPSKLPTEVNHVP
                     SGPSIPADRTVSHLAAAKLDAHSPRPSGPGPSSFPRASHPSSTASTALSTNATVMLAA
                     GIPVPQFISSIHPEQSVIMPPHSITQTVSLSHLSQGEVRMNTPTLPSITYSIRPEALH
                     SPRAPLQPQQIEVRAPQRASTPQPAPAGVPALASQHPPEEEVHYHLPVARATAPVQSE
                     VLVMQSEYRLHPYTVPRDVRIMVHPHVTAVSEQPRAADGVVKVPPASKAPQQPGKEAA
                     KTPDAKAAPTPTPAPVPVPVPLPAPAPAPHGEARILTVTPSNQLQGLPLTPPVVVTHG
                     VQIVHSSGELFQEYRYGDIRTYHPPAQLTHTQFPAASSVGLPSRTKTAAQGPPPEGEP
                     LQPPQPVQSTQPAQPAPPCPPSQLGQPGQPPSSKMPQVSQEAKGTQTGVEQPRLPAGP
                     ANRPPEPHTQVQRAQAETGPTSFPSPVSVSMKPDLPVSLPTQTAPKQPLFVPTTSGPS
                     TPPGLVLPHTEFQPAPKQDSSPHLTSQRPVDMVQLLKKYPIVWQGLLALKNDTAAVQL
                     HFVSGNNVLAHRSLPLSEGGPPLRIAQRMRLEATQLEGVARRMTVETDYCLLLALPCG
                     RDQEDVVSQTESLKAAFITYLQAKQAAGIINVPNPGSNQPAYVLQIFPPCEFSESHLS
                     RLAPDLLASISNISPHLMIVIASV"
     exon            445..765
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            766..1242
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            1243..1403
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            1404..1604
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            1605..1756
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            1757..1882
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            1883..1996
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            1997..2110
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            2111..2211
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            2212..10387
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            10388..10870
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            10871..11065
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            11066..11224
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     exon            11225..12385
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /inference="alignment:Splign:2.1.0"
     regulatory      12366..12371
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /note="hexamer: ATTAAA"
     polyA_site      12385
                     /gene="SPEN"
                     /gene_synonym="HIAA0929; MINT; RATARS; RBM15C; SHARP"
                     /note="major polyA site"
ORIGIN      
        1 agtgggaagc gtccggctgc cacagcgcca gctccgtcgt agtcgctgcc gcccgtgtcc
       61 cgctcgcccc tcctcccgct cccccgcccg cccctgcccg ggcgcatgcg ctgccggagc
      121 gcgagggtcg gcttcgggtg tgtggtggcg gcagagctga gctgcgaggc ccgagagtca
      181 gaacctgggg gagagggatg gtctctgcac gggggggagc cggaggagcc gccgccgctg
      241 ccgacgccac cgccgcagcc gccgccgccg ccgccccggc acccgcctcc cggcgctgac
      301 ggtctcgtac gaagccggcg agggggagcc agcagcggcg gtcgccggca cgccgcccag
      361 catggtccgg gaaaccaggc atctctgggt gggcaactta cccgagaacg tgcgggaaga
      421 gaagatcatc gagcatttca aacgatatgg ccgcgtggaa agtgtcaaaa ttcttcccaa
      481 gaggggatct gaaggaggag tggctgcctt tgtggatttt gtggacatca aaagtgcaca
      541 gaaagctcac aactcggtca acaaaatggg tgacagagac ctacgcacgg attataatga
      601 accaggcacc atcccgagtg ctgctcgggg attggatgat acagtttcca tagcatctcg
      661 tagtagagag gtttctgggt tcagaggagg tggtggaggg cctgcttatg gtcccccacc
      721 gtcacttcat gcacgagaag gacgttatga gcggagactt gatggggctt cagataacag
      781 ggagcgtgct tatgaacata gtgcctatgg acaccatgaa cgggggacgg gaggatttga
      841 tcggacaaga cattacgatc aggattacta tagagatcct cgagagcgga ctttacaaca
      901 tgggctctat tacgcttctc ggagtcgaag tccaaatcgc tttgatgctc atgacccccg
      961 atatgaacct agggctcgcg agcagtttac actgcccagt gtggtacaca gggatatcta
     1021 cagggatgat attacccggg aggtacgagg cagaaggcca gagcggaatt accagcacag
     1081 caggagtcgg tcaccacatt catcccagtc tagaaatcag tctcctcaga gactggctag
     1141 ccaagcatct agacccacaa ggtcccctag cggcagcggc tctagaagta gatcctccag
     1201 tagtgattca atcagcagca gcagtagtac cagcagtgac agcagtgatt ccagcagtag
     1261 ttcaagtgat gattctccag ctcgatcagt tcagtctgca gcagtccctg cacccacttc
     1321 ccagttgctt tcatctctgg aaaaagatga gccccgtaaa agttttggca tcaaggtcca
     1381 gaatcttcca gtacgctcta cagatacaag ccttaaagat ggccttttcc atgaatttaa
     1441 gaaatttgga aaagtaactt cagtgcagat acatggaact tcagaagaga ggtatggtct
     1501 ggtattcttt cggcagcaag aggaccaaga aaaagccttg actgcatcaa aaggaaaact
     1561 tttctttggc atgcagattg aagtaacagc atggataggt ccagaaacag aaagtgaaaa
     1621 tgaatttcgc cccttggatg aaaggataga tgaatttcac cccaaagcaa caagaactct
     1681 ctttattggc aaccttgaaa aaaccactac ttaccatgac cttcgcaaca tcttccagcg
     1741 ctttggagaa attgtggata ttgacattaa gaaagtaaat ggagttcctc agtatgcgtt
     1801 tctgcaatac tgtgatattg ctagcgtttg taaagctatt aagaagatgg atggggaata
     1861 tcttggaaat aatcgcctca agctgggttt tggaaagagc atgcctacaa actgcgtgtg
     1921 gctagatggg ctttcttcga atgtgtcaga tcagtattta acacgacatt tctgccgata
     1981 tgggcctgtg gtaaaggtgg tgtttgaccg cttaaaaggc atggccctgg ttctctacaa
     2041 tgaaattgaa tatgcacaag cagctgtaaa agagaccaaa gggaggaaaa tcggtgggaa
     2101 taaaattaag gtggattttg caaatcggga aagtcagctg gctttttatc actgcatgga
     2161 gaaatctggt caagacatca gagactttta tgaaatgtta gccgaaagaa gagaggaacg
     2221 aagggcatcc tacgactata accaagatcg tacatattat gagagtgttc gaactccagg
     2281 cacttatcct gaggattcca ggcgggacta tccagctcga gggagagagt tttattcaga
     2341 atgggaaact taccaaggag actactatga atcacgatac tacgatgatc ctcgggaata
     2401 cagggattac aggaatgatc cttatgaaca agatattagg gaatatagtt acaggcaaag
     2461 ggaacgagaa agagaacgtg aaagatttga gtctgaccgg gacagagacc atgagaggag
     2521 gccgattgaa cgaagtcaaa gtcctgttca cttgcgacgt ccacagagtc ctggagcgtc
     2581 tccctctcag gcagagaggt tgccgagtga ttctgagagg aggctttaca gccgatcctc
     2641 agaccggagt ggaagctgta gctcactctc ccctccaaga tatgagaaac tggacaagtc
     2701 tcgtttggag cgctatacaa aaaatgaaaa gacagataaa gaacgaactt ttgatccgga
     2761 gagagtggag agagagagac gcttaatacg gaaggaaaaa gtggaaaagg acaaaactga
     2821 caagcagaaa cgcaaaggaa aggttcactc ccctagttct cagtcttcag aaacggacca
     2881 agaaaatgag cgagagcaaa gccctgaaaa gcccaggagt tgtaataaac tgagcagaga
     2941 gaaagctgac aaagagggaa tagcgaaaaa ccgcctggaa ctcatgcctt gcgtggtttt
     3001 gactcgagtg aaagagaaag agggaaaggt cattgaccac actcctgtgg aaaagttgaa
     3061 agccaagctt gataatgaca ctgtcaaatc ttctgccctg gaccagaaac ttcaggtctc
     3121 tcagacggag cctgcaaaat ctgacttgtc taaactggaa tcagttagaa tgaaagtacc
     3181 aaaggaaaag gggctttcaa gccatgttga agtggtggag aaggaaggca ggcttaaagc
     3241 caggaagcac ctcaagcctg agcagcctgc agatggggta agtgctgtgg atctggagaa
     3301 gctggaagcc aggaaaaggc gctttgcaga ttccaattta aaagcagaaa agcaaaaacc
     3361 agaggtcaag aaaagcagtc cagagatgga ggatgctcgc gtgctttcaa aaaagcagcc
     3421 tgacgtgtcc tctagagagg tcattctgct gagggaagga gaggctgaaa gaaagcctgt
     3481 gaggaaagaa attcttaaaa gagaatctaa aaaaatcaaa ctggacagac ttaatactgt
     3541 tgccagcccc aaagactgtc aggagcttgc cagtatttct gttgggtctg gctcaaggcc
     3601 cagctcagac ctacaagcaa gactgggaga actagcaggt gaatctgtgg aaaatcaaga
     3661 agtccaatca aaaaagccca ttccctcaaa accacagctc aaacagctgc aggtattaga
     3721 tgatcaagga ccagagagag aagacgttag gaaaaactat tgcagtcttc gtgatgaaac
     3781 acctgaacgt aaatcaggcc aagagaaatc acattcagta aatactgaag aaaaaattgg
     3841 cattgacatc gatcacacgc agagttaccg aaaacaaatg gaacagagtc gtaggaaaca
     3901 gcagatggaa atggaaatag ccaagtctga gaagtttggc agtcctaaaa aagatgtaga
     3961 tgaatatgaa agacgtagcc tcgttcacga ggtaggcaaa ccccctcaag atgtcactga
     4021 tgactctcct cctagcaaaa agaaaaggat ggatcatgtc gattttgata tctgcaccaa
     4081 gcgagaacgg aattacagaa gttcacgcca aatcagcgaa gattctgaaa ggactggtgg
     4141 ttctcccagt gtccgacatg gttccttcca tgaagatgag gatcccatag gctcccctag
     4201 gctactgtca gtaaaagggt ctcctaaagt agatgaaaaa gtcctcccct attctaacat
     4261 aacagtcagg gaagagtctt taaaatttaa tccttatgat tctagcagga gagaacagat
     4321 ggcagatatg gccaaaataa aactatctgt cttgaattct gaagatgaac taaatcgttg
     4381 ggactctcag atgaaacagg atgctggcag atttgatgtg agtttcccaa acagcataat
     4441 taagagagat agccttcgaa aaaggtctgt acgagatctg gaacctggtg aggtgccttc
     4501 tgattctgac gaagatggtg aacacaaatc ccactcaccc agagcctctg cattatatga
     4561 aagttctcga ttgtcttttt tattgaggga cagagaagac aagctacgtg agcgagatga
     4621 aagactctct agttctttag aaaggaacaa attttactct tttgcattgg ataagacaat
     4681 cacaccagac actaaagctt tgcttgaaag agctaaatcc ctctcttcat ctcgtgaaga
     4741 aaattggtct tttcttgatt gggactcccg atttgcaaat tttcgaaaca acaaagataa
     4801 agaaaaggtt gactctgctc caagacctat tccatcctgg tacatgaaaa agaagaaaat
     4861 taggactgat tcagaaggga aaatggatga taagaaagag gaccataaag aagaagagca
     4921 agagaggcag gaattgtttg cttctcgttt tttacacagc tcaatctttg aacaagattc
     4981 caagcgattg cagcatctag agagaaaaga ggaagattct gacttcattt ctggtaggat
     5041 ctatgggaag cagacatctg agggagcaaa cagcacaact gattccattc aagaaccagt
     5101 agttctgttc catagcagat ttatggagct cacacggatg caacagaaag aaaaagaaaa
     5161 agaccagaaa cccaaagagg ttgagaaaca ggaagataca gagaatcatc ccaagacccc
     5221 agaatctgct cctgagaata aagattcaga actgaaaact ccaccttccg ttgggcctcc
     5281 aagtgtcaca gtcgtaactc tagaatcagc cccatcagca ctagagaaga ccactggtga
     5341 caaaacggta gaggcgcctt tggtaacaga agagaagact gtggagccag ctaccgtctc
     5401 agaagaagca aagcctgcat ctgaacctgc tcctgcccct gtggaacagc tggaacaagt
     5461 agacctgccc ccaggagcag accccgataa agaagctgcc atgatgcctg cgggtgttga
     5521 ggaaggttca tcaggtgacc agccgcctta tctggatgcc aagcctccaa ctcccggggc
     5581 ctcgttttcc caggcagaga gcaacgtaga tccagagcct gacagtaccc agccactttc
     5641 aaaaccagct cagaagtctg aggaagccaa tgagccaaag gccgaaaagc cagacgccac
     5701 tgcagatgct gagcctgatg caaaccagaa agccgaagct gctcctgagt ctcagccccc
     5761 agcttctgaa gatttagagg ttgatcctcc agttgctgca aaggataaaa agccaaacaa
     5821 aagcaagcgt tcaaagaccc ctgttcaggc agctgcagtg agtatcgtgg agaagcccgt
     5881 cacaaggaag agtgagagga tagaccggga aaaactcaag cggtccaatt ctcctcgggg
     5941 agaagcacag aagcttttgg aattgaagat ggaggcagag aagattacaa ggactgcttc
     6001 taaaaactct gctgcagacc ttgaacatcc cgaaccaagt ttgcctctca gccgaacaag
     6061 gcgccggaat gtaaggagcg tctatgcaac catgggtgac catgaaaacc gctctcctgt
     6121 caaagagccc gttgagcaac caagagtgac cagaaagaga ttggagcgag agcttcagga
     6181 ggctgcagcg gttcccacca cccctcggag gggaaggcct ccaaagacac gccggcgagc
     6241 cgatgaagag gaggagaacg aggccaagga acctgcagaa acactcaagc cacctgaggg
     6301 atggcggtcg ccaaggtccc agaaaactgc agctggtggt ggaccccaag ggaaaaaggg
     6361 aaaaaatgaa ccgaaggtgg atgctacacg tcctgaggcc accactgagg tgggccccca
     6421 aataggcgtg aaagagagct ccatggaacc caaggctgct gaggaggagg cagggagtga
     6481 acagaaacgt gacagaaaag atgctggcac agacaaaaac ccccctgaaa ccgcccctgt
     6541 tgaagttgta gagaaaaaac cggcccctga aaaaaactcc aaatcaaaga gaggaagatc
     6601 tcgaaactcc aggttagcag tggacaaatc tgcaagtctg aaaaatgtgg atgctgctgt
     6661 cagtcccagg ggggctgcag cacaggcagg ggagagggaa tctggggtgg tggcagtctc
     6721 ccctgagaaa agtgagagtc cccaaaagga ggatggttta tcatcccagt tgaaaagtga
     6781 tccagttgat ccagacaagg aaccagagaa agaagacgtg tctgcctctg ggccgtcccc
     6841 agaagccacc cagttagcca agcagatgga gctggagcag gccgtggaac acatcgcaaa
     6901 gctcgctgag gcctctgcct ctgctgccta taaggcagat gcaccagagg gccttgcccc
     6961 agaggacagg gacaagcctg cacaccaagc aagtgaaaca gagctggctg cggccatcgg
     7021 ctccatcatc aatgacattt ctggggagcc agaaaacttc ccagcacctc caccttatcc
     7081 tggagaatcc cagacagatc tgcaaccccc cgcaggtgca caggcgctgc agccttctga
     7141 ggaaggaatg gagacagatg aggctgtatc tggcatcctg gaaactgagg ctgctacaga
     7201 atcttctagg cctccagtca atgctcctga cccctcagcc ggcccaacag ataccaagga
     7261 agccagagga aatagcagtg aaacctcaca ctcagtgcca gaagccaaag ggtctaaaga
     7321 agtggaagtc actcttgttc ggaaagacaa agggcgccag aaaacaaccc gatcacgccg
     7381 caagcgaaac acaaacaaga aagtggtggc tcctgtagag agccatgtcc ctgaatccaa
     7441 ccaagctcaa ggtgagagtc ctgctgcaaa tgaggggaca acagtacagc accccgaagc
     7501 cccacaggaa gaaaagcaga gtgagaaacc ccattccact cctcctcagt catgtacttc
     7561 tgacctaagc aagattccct ccacagagaa ttcgtcccaa gaaatcagtg ttgaggaaag
     7621 gactccaacc aaagcatctg tgcccccaga ccttccccca cctccccagc cagcaccggt
     7681 ggatgaggag cctcaagcca ggttcagggt gcattccatc attgaaagtg acccggtgac
     7741 cccacccagc gatccaagca tccccatacc cacactgcct tctgtaactg cagcaaagct
     7801 ctcacctcct gtcgcctctg gggggatccc acaccagagc ccccctacta aggtgacaga
     7861 gtggatcaca aggcaggagg agccacgggc tcagtctact ccatctccag ctcttccccc
     7921 agacacaaag gcctctgatg ttgacaccag ctccagcacc ctgaggaaga ttctcatgga
     7981 ccccaagtat gtgtctgcca caagtgtcac ttccacaagt gtcaccacag ccattgcaga
     8041 gcctgtcagt gctgcccctt gcctacatga ggccccgccc ccgccagttg actctaaaaa
     8101 gcctttagaa gaaaaaacag cacctccagt gacaaacaac tctgagatac aagcctcgga
     8161 ggtgctggta gctgctgaca aggaaaaggt ggctccagtc attgctccca aaattacctc
     8221 tgttattagc cggatgcctg tcagcattga cctggaaaat tcacagaaga taaccttggc
     8281 aaaaccagct cctcaaaccc tcactggtct ggtgagcgca ctcactggcc tggtgaacgt
     8341 ctccctggtc ccggtgaatg ccctgaaagg ccccgtgaag ggctcagtga ccacactgaa
     8401 aagtttggtg agcacccctg ctgggcccgt gaacgtcctg aaagggcctg tgaatgttct
     8461 tacggggcca gtgaatgttc tcaccactcc agtgaacgcc acggtgggca cagtgaatgc
     8521 cgccccaggc acagtcaatg ccgctgcgag tgcagtgaat gccacagcaa gtgcagtgac
     8581 cgtcacagcg ggtgcggtta ctgctgcatc tggtggtgta acggccacaa caggcacggt
     8641 gacaatggca ggggcagtga ttgcgccgtc aacaaagtgc aaacagagag cgagtgctaa
     8701 tgaaaacagt cggttccacc cagggtccat gcctgtgatc gacgatcgtc cggcagacgc
     8761 gggctcaggg gcggggctgc gtgtgaacac ttctgaaggg gttgtgctcc tgagttactc
     8821 agggcagaag accgaaggcc cacagcggat cagcgccaag atcagccaga tccccccggc
     8881 cagtgcaatg gacattgaat ttcagcagtc agtgtccaag tcccaggtca aacctgattc
     8941 tgtcacagca tcgcagcctc catccaaagg ccctcaagct cctgcaggct atgcgaacgt
     9001 ggccacccat tccacgttgg tactgaccgc ccagacatat aatgcctctc ctgtgatttc
     9061 gtctgtgaag gccgataggc catccttgga gaagcccgag cccattcacc tctcggtgtc
     9121 cacgcctgtc acccagggag gcacagtgaa ggttctcacc caggggatca acacaccccc
     9181 tgtgctggtt cacaaccagc tggtcctcac cccaagcatt gtcaccacaa acaagaagct
     9241 tgctgacccc gtcaccctta aaatcgagac caaggtcctt cagccggcca acctggggtc
     9301 cacgctcacg ccccaccacc ctcctgctct gcccagcaaa ctgcctacag aagtcaacca
     9361 tgtcccctcg gggcccagca tcccagcaga tcgaactgtc tcccatttgg cagctgcaaa
     9421 gctagatgct cattctcctc gaccaagtgg acccgggcca tcctcattcc caagggcaag
     9481 ccaccccagc agtactgcat ctacggcgct ctccaccaac gccacagtca tgctggctgc
     9541 aggcatccca gtgccccagt tcatctccag catccaccca gagcagtctg tcatcatgcc
     9601 accccacagc atcacccaga ctgtgtccct gagccacctc tcccagggcg aggtgagaat
     9661 gaacactccc acgctgccca gtatcaccta cagcatccgg ccagaagcgc ttcactctcc
     9721 tcgggctccg ctgcagcccc agcaaataga ggtcagggcc ccacagcgtg ccagcacccc
     9781 gcagccagcc ccagctggtg tgcctgcact ggcctcccag caccctcccg aggaggaagt
     9841 gcattatcac cttcctgtcg ctcgagccac agcccctgtg cagtcagagg tactagtcat
     9901 gcagtctgag taccgactgc acccctatac tgtgccacgg gatgtgagga tcatggtgca
     9961 tccacatgtg acggcagtca gcgagcagcc cagggccgcg gatggggtgg tgaaggtgcc
    10021 accagccagc aaggcccctc agcagccagg gaaggaagct gccaagacac cagatgccaa
    10081 agctgccccc acccccaccc ctgcccccgt ccctgtccct gtcccccttc ctgcccctgc
    10141 tcctgcccct catggtgagg cccgtatcct cacagttacc cccagtaacc aactccaggg
    10201 gctgcctctg acccctcctg tggtggtgac ccatggggtg cagattgtgc actccagcgg
    10261 ggagctgttt caagagtacc ggtacggcga catccgcacc taccaccccc cggcccagct
    10321 cacacacact cagtttcccg ccgcttcctc tgttggcctg ccttcccgga ccaagacagc
    10381 tgctcagggc cctcctcctg aaggtgagcc cctgcagcct cctcagcctg tgcagtccac
    10441 acagcctgcc cagcctgcac caccctgccc gccctcccag ctcggtcagc ccggccagcc
    10501 accaagcagc aagatgcctc aagtgtccca ggaggcaaag gggacccaga cgggagtaga
    10561 gcagcctcgc ctcccagctg gacctgcaaa caggccacct gagcctcaca cccaggttca
    10621 gagggcacaa gcagaaacag gcccgacttc cttcccctcc cctgtgtctg tctccatgaa
    10681 gcctgacctt ccagtctctc ttcccactca gactgcccca aaacagccgt tgtttgtccc
    10741 aacaacctct ggccccagca ccccaccagg actggttctg ccacacactg aattccagcc
    10801 agcccccaaa caagattcct ctccacacct gacttcccag agacccgtgg atatggttca
    10861 acttctgaag aagtacccca tcgtgtggca gggcctgctg gccctcaaga atgacacagc
    10921 tgctgtgcag ctccacttcg tctctggcaa caacgtcctg gcccatcggt ccctgcccct
    10981 ttctgaagga gggcccccac taaggatcgc ccagaggatg cggctggagg caacgcagct
    11041 ggaaggggtt gcccgaagga tgacggtgga gacagattac tgtctgctgc tggctctgcc
    11101 ctgtggccgt gaccaagagg atgttgtgag ccagaccgag tccctcaagg ctgccttcat
    11161 cacttacctg caggccaagc aggcggcagg gatcatcaac gttcccaacc ctggctccaa
    11221 tcagcctgcc tacgtgctgc agatcttccc gccctgtgag ttctctgaga gtcacctgtc
    11281 ccgcctggcc cctgacctcc ttgccagcat ctccaacatc tctccccacc tcatgattgt
    11341 cattgcctcc gtgtgagcca ctgagtggtt atcacctcag tgaatcttcc cagggctctg
    11401 cagtaaaaac aaaggacaac ccagccaagc agaggaagaa gctgccgaag gggacagact
    11461 ccactgccag acggccagcc gtttgctgtc ctgccgcccg gctcagtcgg ccagacttcc
    11521 tctaggagtg gtgctgctac cttgtatgtt tacataatgc tttagcccaa ggacacatca
    11581 ccaacccatg gactcgcaga caccggggct gggtttctct ttcctctttt tggagaaaag
    11641 gaacagggca gtggaatgaa aattttttgt ttgtttgttt ttaagaaaca agaaaacaga
    11701 actgcctttg cactaaatta gtgacttgga cttttgccca gtgaagacag gctgtgacac
    11761 tctggatgtc ttggtgtgtg tagacacaca ttgcagactc ttaacgcagg aaggacttca
    11821 aacttctgct gagaccttgg ggtcaaggaa catttcattg gttttttttg tccaccccca
    11881 tctcccttgc tcatttggat gcgtcacctt aattctcctg ctgccaccgt ctttgattca
    11941 ccgggatgta cagtttacag ttgaagagca aacagaaagg ttttctcttg gtgggatatg
    12001 cagaacttgg gatgtgtgta tatataaata tataatatat ataaatatat ataatactga
    12061 cttaaaaaat caaatccccc gacatacgtt ttttttaatc tgtgccaaaa atgtgttttc
    12121 agaggaaatc ttattttcat attcagactt tgtattgccc actcatttgt ataagtgcgc
    12181 ttcggtacag cacgggtcct gctcccgcga tgtggaagtg tcacacggca cctgtacaaa
    12241 aagactggct aacccctctt cctattacct tgatctcttc ccccaacttc ctaacactta
    12301 ttaatttatg aaactgtttt tctcagcgca gttttgtttt gtgtgtccat tggattacaa
    12361 actttattaa aaaatataaa acaca
//
