LOCUS       NM_006445               7280 bp    mRNA    linear   PRI 20-FEB-2025
DEFINITION  Homo sapiens pre-mRNA processing factor 8 (PRPF8), mRNA.
ACCESSION   NM_006445 XM_005256414
VERSION     NM_006445.4
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 7280)
  AUTHORS   Khoroshkin,M., Buyan,A., Dodel,M., Navickas,A., Yu,J., Trejo,F.,
            Doty,A., Baratam,R., Zhou,S., Lee,S.B., Joshi,T., Garcia,K.,
            Choi,B., Miglani,S., Subramanyam,V., Modi,H., Carpenter,C.,
            Markett,D., Corces,M.R., Mardakheh,F.K., Kulakovskiy,I.V. and
            Goodarzi,H.
  TITLE     Systematic identification of post-transcriptional regulatory
            modules
  JOURNAL   Nat Commun 15 (1), 7872 (2024)
   PUBMED   39251607
  REMARK    Erratum:[Nat Commun. 2024 Oct 28;15(1):9277. doi:
            10.1038/s41467-024-52903-4.. PMID: 39468017]
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 7280)
  AUTHORS   Atkinson,R., Georgiou,M., Yang,C., Szymanska,K., Lahat,A.,
            Vasconcelos,E.J.R., Ji,Y., Moya Molina,M., Collin,J., Queen,R.,
            Dorgau,B., Watson,A., Kurzawa-Akanbi,M., Laws,R., Saxena,A., Shyan
            Beh,C., Siachisumo,C., Goertler,F., Karwatka,M., Davey,T.,
            Inglehearn,C.F., McKibbin,M., Luhrmann,R., Steel,D.H.,
            Elliott,D.J., Armstrong,L., Urlaub,H., Ali,R.R., Grellscheid,S.N.,
            Johnson,C.A., Mozaffari-Jovin,S. and Lako,M.
  TITLE     PRPF8-mediated dysregulation of hBrr2 helicase disrupts human
            spliceosome kinetics and 5 -splice-site selection causing
            tissue-specific defects
  JOURNAL   Nat Commun 15 (1), 3138 (2024)
   PUBMED   38605034
  REMARK    GeneRIF: PRPF8-mediated dysregulation of hBrr2 helicase disrupts
            human spliceosome kinetics and 5 -splice-site selection causing
            tissue-specific defects.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 7280)
  AUTHORS   Sun,Y., Zhang,L., Fang,Z., Liu,D., Shao,M., Liu,Y., Liao,B. and
            Jin,Y.
  TITLE     PRPF8 controls alternative splicing of PIRH2 to modulate the p53
            pathway and survival of human ESCs
  JOURNAL   J Cell Physiol 238 (8), 1909-1920 (2023)
   PUBMED   37357506
  REMARK    GeneRIF: PRPF8 controls alternative splicing of PIRH2 to modulate
            the p53 pathway and survival of human ESCs.
REFERENCE   4  (bases 1 to 7280)
  AUTHORS   Lopez-Canovas,J.L., Herman-Sanchez,N., Del Rio-Moreno,M.,
            Fuentes-Fayos,A.C., Lara-Lopez,A., Sanchez-Frias,M.E., Amado,V.,
            Ciria,R., Briceno,J., de la Mata,M., Castano,J.P.,
            Rodriguez-Peralvarez,M., Luque,R.M. and Gahete,M.D.
  TITLE     PRPF8 increases the aggressiveness of hepatocellular carcinoma by
            regulating FAK/AKT pathway via fibronectin 1 splicing
  JOURNAL   Exp Mol Med 55 (1), 132-142 (2023)
   PUBMED   36609600
  REMARK    GeneRIF: PRPF8 increases the aggressiveness of hepatocellular
            carcinoma by regulating FAK/AKT pathway via fibronectin 1 splicing.
REFERENCE   5  (bases 1 to 7280)
  AUTHORS   Preussner,M., Santos,K.F., Alles,J., Heroven,C., Heyd,F., Wahl,M.C.
            and Weber,G.
  TITLE     Structural and functional investigation of the human snRNP assembly
            factor AAR2 in complex with the RNase H-like domain of PRPF8
  JOURNAL   Acta Crystallogr D Struct Biol 78 (Pt 11), 1373-1383 (2022)
   PUBMED   36322420
  REMARK    GeneRIF: Structural and functional investigation of the human snRNP
            assembly factor AAR2 in complex with the RNase H-like domain of
            PRPF8.
REFERENCE   6  (bases 1 to 7280)
  AUTHORS   Fahim,A.T., Daiger,S.P. and Weleber,R.G.
  TITLE     Nonsyndromic Retinitis Pigmentosa Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301590
REFERENCE   7  (bases 1 to 7280)
  AUTHORS   Garcia-Blanco,M.A., Anderson,G.J., Beggs,J. and Sharp,P.A.
  TITLE     A mammalian protein of 220 kDa binds pre-mRNAs in the spliceosome:
            a potential homologue of the yeast PRP8 protein
  JOURNAL   Proc Natl Acad Sci U S A 87 (8), 3082-3086 (1990)
   PUBMED   2139226
REFERENCE   8  (bases 1 to 7280)
  AUTHORS   Anderson,G.J., Bach,M., Luhrmann,R. and Beggs,J.D.
  TITLE     Conservation between yeast and man of a protein associated with U5
            small nuclear ribonucleoprotein
  JOURNAL   Nature 342 (6251), 819-821 (1989)
   PUBMED   2532307
REFERENCE   9  (bases 1 to 7280)
  AUTHORS   Pinto,A.L. and Steitz,J.A.
  TITLE     The mammalian analogue of the yeast PRP8 splicing protein is
            present in the U4/5/6 small nuclear ribonucleoprotein particle and
            the spliceosome
  JOURNAL   Proc Natl Acad Sci U S A 86 (22), 8742-8746 (1989)
   PUBMED   2479028
REFERENCE   10 (bases 1 to 7280)
  AUTHORS   Bach,M., Winkelmann,G. and Luhrmann,R.
  TITLE     20S small nuclear ribonucleoprotein U5 shows a surprisingly complex
            protein composition
  JOURNAL   Proc Natl Acad Sci U S A 86 (16), 6038-6042 (1989)
   PUBMED   2527369
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CD698473.1, DB081408.1 and
            BC064370.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_006445.3.
            
            Summary: Pre-mRNA splicing occurs in 2 sequential
            transesterification steps. The protein encoded by this gene is a
            component of both U2- and U12-dependent spliceosomes, and found to
            be essential for the catalytic step II in pre-mRNA splicing
            process. It contains several WD repeats, which function in
            protein-protein interactions. This protein has a sequence
            similarity to yeast Prp8 protein. This gene is a candidate gene for
            autosomal dominant retinitis pigmentosa. [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 :: BC064370.1, SRR1803615.266153.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000304992.11/ ENSP00000304350.6
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-494               CD698473.1         38-531
            495-870             DB081408.1         174-549
            871-7280            BC064370.1         851-7260
FEATURES             Location/Qualifiers
     source          1..7280
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17p13.3"
     gene            1..7280
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /note="pre-mRNA processing factor 8"
                     /db_xref="GeneID:10594"
                     /db_xref="HGNC:HGNC:17340"
                     /db_xref="MIM:607300"
     exon            1..88
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            89..199
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     CDS             100..7107
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /note="U5 snRNP-specific protein (220 kD), ortholog of S.
                     cerevisiae Prp8p; precursor mRNA processing protein;
                     splicing factor Prp8; apoptosis-regulated protein 2;
                     apoptosis-regulated protein 1; p220; PRP8 homolog; 220 kDa
                     U5 snRNP-specific protein; PRP8 pre-mRNA processing factor
                     8 homolog"
                     /codon_start=1
                     /product="pre-mRNA-processing-splicing factor 8"
                     /protein_id="NP_006436.3"
                     /db_xref="CCDS:CCDS11010.1"
                     /db_xref="GeneID:10594"
                     /db_xref="HGNC:HGNC:17340"
                     /db_xref="MIM:607300"
                     /translation="MAGVFPYRGPGNPVPGPLAPLPDYMSEEKLQEKARKWQQLQAKR
                     YAEKRKFGFVDAQKEDMPPEHVRKIIRDHGDMTNRKFRHDKRVYLGALKYMPHAVLKL
                     LENMPMPWEQIRDVPVLYHITGAISFVNEIPWVIEPVYISQWGSMWIMMRREKRDRRH
                     FKRMRFPPFDDEEPPLDYADNILDVEPLEAIQLELDPEEDAPVLDWFYDHQPLRDSRK
                     YVNGSTYQRWQFTLPMMSTLYRLANQLLTDLVDDNYFYLFDLKAFFTSKALNMAIPGG
                     PKFEPLVRDINLQDEDWNEFNDINKIIIRQPIRTEYKIAFPYLYNNLPHHVHLTWYHT
                     PNVVFIKTEDPDLPAFYFDPLINPISHRHSVKSQEPLPDDDEEFELPEFVEPFLKDTP
                     LYTDNTANGIALLWAPRPFNLRSGRTRRALDIPLVKNWYREHCPAGQPVKVRVSYQKL
                     LKYYVLNALKHRPPKAQKKRYLFRSFKATKFFQSTKLDWVEVGLQVCRQGYNMLNLLI
                     HRKNLNYLHLDYNFNLKPVKTLTTKERKKSRFGNAFHLCREVLRLTKLVVDSHVQYRL
                     GNVDAFQLADGLQYIFAHVGQLTGMYRYKYKLMRQIRMCKDLKHLIYYRFNTGPVGKG
                     PGCGFWAAGWRVWLFFMRGITPLLERWLGNLLARQFEGRHSKGVAKTVTKQRVESHFD
                     LELRAAVMHDILDMMPEGIKQNKARTILQHLSEAWRCWKANIPWKVPGLPTPIENMIL
                     RYVKAKADWWTNTAHYNRERIRRGATVDKTVCKKNLGRLTRLYLKAEQERQHNYLKDG
                     PYITAEEAVAVYTTTVHWLESRRFSPIPFPPLSYKHDTKLLILALERLKEAYSVKSRL
                     NQSQREELGLIEQAYDNPHEALSRIKRHLLTQRAFKEVGIEFMDLYSHLVPVYDVEPL
                     EKITDAYLDQYLWYEADKRRLFPPWIKPADTEPPPLLVYKWCQGINNLQDVWETSEGE
                     CNVMLESRFEKMYEKIDLTLLNRLLRLIVDHNIADYMTAKNNVVINYKDMNHTNSYGI
                     IRGLQFASFIVQYYGLVMDLLVLGLHRASEMAGPPQMPNDFLSFQDIATEAAHPIRLF
                     CRYIDRIHIFFRFTADEARDLIQRYLTEHPDPNNENIVGYNNKKCWPRDARMRLMKHD
                     VNLGRAVFWDIKNRLPRSVTTVQWENSFVSVYSKDNPNLLFNMCGFECRILPKCRTSY
                     EEFTHKDGVWNLQNEVTKERTAQCFLRVDDESMQRFHNRVRQILMASGSTTFTKIVNK
                     WNTALIGLMTYFREAVVNTQELLDLLVKCENKIQTRIKIGLNSKMPSRFPPVVFYTPK
                     ELGGLGMLSMGHVLIPQSDLRWSKQTDVGITHFRSGMSHEEDQLIPNLYRYIQPWESE
                     FIDSQRVWAEYALKRQEAIAQNRRLTLEDLEDSWDRGIPRINTLFQKDRHTLAYDKGW
                     RVRTDFKQYQVLKQNPFWWTHQRHDGKLWNLNNYRTDMIQALGGVEGILEHTLFKGTY
                     FPTWEGLFWEKASGFEESMKWKKLTNAQRSGLNQIPNRRFTLWWSPTINRANVYVGFQ
                     VQLDLTGIFMHGKIPTLKISLIQIFRAHLWQKIHESIVMDLCQVFDQELDALEIETVQ
                     KETIHPRKSYKMNSSCADILLFASYKWNVSRPSLLADSKDVMDSTTTQKYWIDIQLRW
                     GDYDSHDIERYARAKFLDYTTDNMSIYPSPTGVLIAIDLAYNLHSAYGNWFPGSKPLI
                     QQAMAKIMKANPALYVLRERIRKGLQLYSSEPTEPYLSSQNYGELFSNQIIWFVDDTN
                     VYRVTIHKTFEGNLTTKPINGAIFIFNPRTGQLFLKIIHTSVWAGQKRLGQLAKWKTA
                     EEVAALIRSLPVEEQPKQIIVTRKGMLDPLEVHLLDFPNIVIKGSELQLPFQACLKVE
                     KFGDLILKATEPQMVLFNLYDDWLKTISSYTAFSRLILILRALHVNNDRAKVILKPDK
                     TTITEPHHIWPTLTDEEWIKVEVQLKDLILADYGKKNNVNVASLTQSEIRDIILGMEI
                     SAPSQQRQQIAEIEKQTKEQSQLTATQTRTVNKHGDEIITSTTSNYETQTFSSKTEWR
                     VRAISAANLHLRTNHIYVSSDDIKETGYTYILPKNVLKKFICISDLRAQIAGYLYGVS
                     PPDNPQVKEIRCIVMVPQWGTHQTVHLPGQLPQHEYLKEMEPLGWIHTQPNESPQLSP
                     QDVTTHAKIMADNPSWDGEKTIIITCSFTPGSCTLTAYKLTPSGYEWGRQNTDKGNNP
                     KGYLPSHYERVQMLLSDRFLGFFMVPAQSSWNYNFMGVRHDPNMKYELQLANPKEFYH
                     EVHRPSHFLNFALLQEGEVYSADREDLYA"
     exon            200..368
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            369..533
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            534..752
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            753..965
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            966..1091
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            1092..1197
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            1198..1388
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            1389..1508
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            1509..1698
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            1699..1818
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            1819..1953
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            1954..2083
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            2084..2280
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            2281..2487
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            2488..2651
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            2652..2778
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            2779..2971
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            2972..3159
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            3160..3398
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            3399..3545
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            3546..3756
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            3757..3873
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            3874..4121
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            4122..4301
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            4302..4437
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            4438..4607
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            4608..4737
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            4738..4884
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            4885..5045
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            5046..5237
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            5238..5475
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            5476..5604
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            5605..5718
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            5719..5892
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            5893..6086
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            6087..6326
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            6327..6468
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            6469..6609
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            6610..6749
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            6750..6952
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     exon            6953..7280
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /inference="alignment:Splign:2.1.0"
     regulatory      7259..7264
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /note="hexamer: AATAAA"
     polyA_site      7280
                     /gene="PRPF8"
                     /gene_synonym="HPRP8; PRP8; PRPC8; RP13; SNRNP220"
                     /note="major polyA site"
ORIGIN      
        1 acttcccggc gctgggaacg cggagcggac gcagtctggc cgccattgcg ctgcggggaa
       61 agcggcctct tgtgtgaggg cctgtgggat tctccggata tggccggagt gtttccttat
      121 cgagggccgg gtaacccggt gcctggccct ctagccccgc taccggacta catgtcggag
      181 gagaagctgc aggagaaagc tcgaaaatgg cagcaattgc aggccaagcg ctatgcagaa
      241 aagcggaagt ttgggtttgt ggatgcccag aaggaagaca tgcccccaga acatgtcagg
      301 aagatcattc gagaccatgg agacatgacc aacaggaagt tccgccatga caaaagggtt
      361 tacttgggtg ccctaaagta catgccccac gcagtcctca aactcctgga gaacatgcct
      421 atgccttggg agcagattcg ggatgtgcct gtgctgtacc acatcactgg agccatttcc
      481 ttcgtcaatg agattccctg ggtcattgaa cctgtctaca tctcccagtg ggggtcaatg
      541 tggattatga tgcgccgaga aaaaagagat aggaggcatt tcaagaggat gcgttttccc
      601 ccttttgatg atgaggagcc gcccttggac tatgctgaca acatcctaga tgttgagcca
      661 ctggaggcca ttcagctaga gctggaccct gaggaggacg cccctgtgtt ggactggttc
      721 tatgaccacc agccgttgag ggacagcagg aagtatgtaa atggctccac ttaccagcgc
      781 tggcagttca cactacctat gatgtcgact ctctaccgcc tggctaatca gctcctgaca
      841 gacttggtgg atgacaacta cttctacctg tttgatttga aggccttctt tacgtccaag
      901 gcactcaata tggccattcc tggaggcccc aaatttgaac ctcttgttcg agacatcaac
      961 ctacaggatg aagactggaa tgaattcaat gatattaaca agattatcat ccggcagcct
     1021 atccgcactg agtacaagat tgcttttcct tacttgtaca acaatcttcc acaccatgtc
     1081 cacctcacct ggtaccatac tcccaatgtt gtattcatca aaactgagga tcctgacttg
     1141 ccagctttct actttgaccc tttgatcaac ccaatctccc ataggcactc agtcaagagc
     1201 caggaaccat tgccggatga tgatgaggaa tttgagctcc cggagtttgt ggagcccttc
     1261 ctgaaggaca cacccctcta tacagacaat acagccaatg gcattgccct gctctgggcc
     1321 ccgcggccct tcaacctacg ctctggtcgc acccgtcggg ccctggacat accccttgtc
     1381 aagaactggt atcgggagca ttgtcctgcc gggcagcctg tgaaagtgag ggtctcctac
     1441 cagaagctgc ttaagtacta tgtgctgaat gccctgaagc atcggccccc taaggctcaa
     1501 aagaagaggt atttgttccg ctccttcaaa gccaccaaat tctttcagtc cacaaagctg
     1561 gactgggtgg aggttgggct ccaggtttgc cgccagggct acaacatgct caaccttctc
     1621 attcaccgca aaaacctcaa ctacctgcac ctggactaca acttcaacct caagcctgtg
     1681 aaaacgctca ccaccaagga aagaaagaaa tctcgttttg ggaatgcttt ccacctgtgt
     1741 cgggaagttc tgcgtttgac taagctggtg gtggatagtc acgtgcagta tcggctgggc
     1801 aatgtggatg ccttccagct ggcagatgga ttgcagtata tatttgccca tgttgggcag
     1861 ttgacgggca tgtatcgata caaatacaag ctgatgcgac agattcgcat gtgcaaggac
     1921 ctgaagcatc tcatctatta tcgtttcaac acgggccctg tagggaaggg tcctggctgt
     1981 ggcttctggg ctgccggttg gcgagtctgg ctctttttca tgcgtggcat taccccttta
     2041 ttagagcgat ggcttggcaa cctcctggcc cggcagtttg aaggtcgaca ctcaaagggg
     2101 gtggcaaaga cagtaacaaa gcagcgagtg gagtcacatt ttgaccttga gctgcgggca
     2161 gctgtgatgc atgatattct ggacatgatg cctgagggga tcaagcagaa caaggcccgg
     2221 acaatcctgc agcacctcag tgaagcctgg cgctgctgga aagccaacat tccctggaag
     2281 gtccctgggc tgccgacgcc catagagaat atgatccttc gatacgtgaa ggccaaggct
     2341 gactggtgga ccaacactgc ccactacaac cgagaacgga tccgccgagg ggccactgtg
     2401 gacaagactg tttgtaaaaa gaatctgggc cgcctcaccc ggctctatct gaaggcagaa
     2461 caggagcggc agcacaacta cctgaaggac gggccttaca tcacagcgga ggaagcagtg
     2521 gcagtatata ccaccacagt gcattggttg gaaagccgca ggttttcacc catcccattc
     2581 cccccactct cctataagca tgacaccaag ttgctcatct tggcattgga gcggctcaag
     2641 gaagcttata gtgtgaagtc tcggttgaac cagtctcaga gggaggagct aggtctgatc
     2701 gagcaggcct acgataaccc ccacgaggcg ctgtcccgca tcaagcgtca cctcctcaca
     2761 cagagagcct tcaaagaggt gggcattgag ttcatggatc tgtatagcca cctcgttcca
     2821 gtatatgatg ttgagcccct ggagaagata actgatgctt acctggacca gtacctgtgg
     2881 tatgaagccg acaagcgccg cctgttccca ccctggatta agcctgcaga cacagaacca
     2941 cctccgctgc ttgtttacaa gtggtgtcaa ggcatcaata acctgcagga cgtgtgggag
     3001 acgagtgaag gcgagtgcaa tgtcatgctg gaatcccgct ttgagaagat gtatgagaag
     3061 atcgacttga ctctgctcaa caggctgctg cgcctcatcg tggaccacaa catagccgac
     3121 tacatgacag ccaagaacaa cgtcgtcatc aactataagg acatgaacca tacgaattca
     3181 tatgggatca tcagaggcct gcagtttgcc tcattcatcg tgcagtatta tggcctggtg
     3241 atggatttgc ttgtattggg attgcaccgg gccagtgaga tggctgggcc ccctcagatg
     3301 ccaaatgact ttctcagttt ccaggacata gccactgagg ctgcccaccc catccgtctc
     3361 ttctgcagat acattgatcg catccatatt tttttcaggt tcacagcaga tgaggctcgg
     3421 gacctgattc aacgttacct gacagagcac cctgacccca ataatgaaaa catcgttggc
     3481 tataataaca agaagtgctg gccccgagat gcccgcatgc gcctcatgaa acatgatgtt
     3541 aacttaggcc gggcggtatt ctgggacatc aagaaccgct tgccacggtc agtgactaca
     3601 gttcagtggg agaacagctt cgtgtctgtg tacagtaagg acaaccccaa cctgctgttc
     3661 aacatgtgtg gcttcgagtg ccgcatcctg cctaagtgcc gcaccagcta tgaggagttc
     3721 acccacaagg acggggtctg gaacctgcag aatgaggtta ctaaggagcg cacagctcag
     3781 tgtttcctgc gtgtggacga tgagtcaatg cagcgcttcc acaaccgcgt gcgtcagatt
     3841 ctcatggcct ctgggtccac caccttcacc aagattgtga ataagtggaa tacagctctc
     3901 attggcctta tgacatactt tcgggaggct gtggtgaaca cccaagagct cttggactta
     3961 ctggtgaagt gtgagaacaa aatccagaca cgtatcaaga ttggactcaa ctccaagatg
     4021 ccaagtcggt tccccccggt tgtgttctac acccctaagg agttgggtgg actcggcatg
     4081 ctctcaatgg gccatgtgct catcccccaa tccgacctca ggtggtccaa acagacagat
     4141 gtaggtatca cacactttcg ttcaggaatg agccatgaag aagaccagct cattcccaac
     4201 ttgtaccgct acatacagcc atgggagagc gagttcattg attctcagcg ggtctgggct
     4261 gagtacgcac tcaagaggca agaggccatt gctcagaaca gacgcctgac tttagaagac
     4321 ctagaagatt catgggatcg tggcattcct cgaatcaata ccctcttcca gaaggaccgg
     4381 cacacactgg cttatgataa gggctggcgt gtcagaactg actttaagca gtatcaggtt
     4441 ttgaagcaga atccgttctg gtggacacac cagcggcatg atgggaagct ctggaacctg
     4501 aacaactacc gtacagacat gatccaggcc ctgggcggtg tggaaggcat tctggaacac
     4561 acactcttta agggcactta cttccctacc tgggaggggc ttttctggga gaaggccagt
     4621 ggctttgagg aatctatgaa gtggaagaag ctaactaatg ctcagcgatc aggactgaac
     4681 cagattccca atcgtagatt caccctctgg tggtccccga ccattaatcg agccaatgta
     4741 tatgtaggct ttcaggtgca gctagacctg acgggtatct tcatgcacgg caagatcccc
     4801 acgctgaaga tctctctcat ccagatcttc cgagctcact tgtggcagaa gatccatgag
     4861 agcattgtta tggacttatg tcaggtgttt gaccaggaac ttgatgcact ggaaattgag
     4921 acagtacaaa aggagacaat ccatccccga aagtcatata agatgaactc ttcctgtgca
     4981 gatatcctgc tctttgcctc ctataagtgg aatgtctccc ggccctcatt gctggctgac
     5041 tccaaggatg tgatggacag caccaccacc cagaaatact ggattgacat ccagttgcgc
     5101 tggggggact atgattccca cgacattgag cgctacgccc gggccaagtt cctggactac
     5161 accaccgaca acatgagtat ctacccttcg cccacaggtg tactcatcgc cattgacctg
     5221 gcctataact tgcacagtgc ctatggaaac tggttcccag gcagcaagcc tctcatacaa
     5281 caggccatgg ccaagatcat gaaggcaaac cctgccctgt atgtgttacg tgaacggatc
     5341 cgcaaggggc tacagctcta ttcatctgaa cccactgagc cttatttgtc ttctcagaac
     5401 tatggtgagc tcttctccaa ccagattatc tggtttgtgg atgacaccaa cgtctacaga
     5461 gtgactattc acaagacctt tgaagggaac ttgacaacca agcccatcaa cggagccatc
     5521 ttcatcttca acccacgcac agggcagctg ttcctcaaga taatccacac gtccgtgtgg
     5581 gcgggacaga agcgtttggg gcagttggct aagtggaaga cagctgagga ggtggccgcc
     5641 ctgatccgat ctctgcctgt ggaggagcag cccaagcaga tcattgtcac caggaagggc
     5701 atgctggacc cactggaggt gcacttactg gacttcccca atattgtcat caaaggatcg
     5761 gagctccaac tccctttcca ggcgtgtctc aaggtggaaa aattcgggga tctcatcctt
     5821 aaagccactg agccccagat ggttctcttc aacctctatg acgactggct caagactatt
     5881 tcatcttaca cggccttctc ccgtctcatc ctgattctgc gtgccctaca tgtgaacaac
     5941 gatcgggcaa aagtgatcct gaagccagac aagactacta ttacagaacc acaccacatc
     6001 tggcccactc tgactgacga agaatggatc aaggtcgagg tgcagctcaa ggatctgatc
     6061 ttggctgact acggcaagaa aaacaatgtg aacgtggcat cactgacaca atcagaaatt
     6121 cgagacatca tcctgggtat ggagatctcg gcaccgtcac agcagcggca gcagatcgct
     6181 gagatcgaga agcagaccaa ggaacaatcg cagctgacgg caacacagac tcgcactgtc
     6241 aacaagcatg gcgatgagat catcacctcc accaccagca actatgagac ccagactttc
     6301 tcatccaaga ctgagtggag ggtcagggcc atctctgctg ccaacctgca cctaaggacc
     6361 aatcacatct atgtttcatc tgacgacatc aaggagactg gctacaccta catccttccc
     6421 aagaatgtgc ttaagaagtt catctgcata tctgaccttc gggcccaaat tgcaggatac
     6481 ctatatgggg tgagcccacc agataacccc caggtgaagg agatccgctg cattgtgatg
     6541 gtgccgcagt ggggcactca ccagaccgtg cacctgcctg gccagctgcc ccagcatgag
     6601 tacctcaagg agatggaacc cttaggttgg atccacactc agcccaatga gtccccgcag
     6661 ttatcacccc aggatgtcac cacccatgcc aagatcatgg ctgacaaccc atcttgggat
     6721 ggcgagaaga ccattatcat cacatgcagc ttcacgccag gctcctgtac actgacggcc
     6781 tacaagctga cccccagtgg ctacgaatgg ggccgccaga acacagacaa gggcaacaac
     6841 cccaagggct acctgccttc acactatgag agggtgcaga tgctgctgtc ggaccgtttc
     6901 cttggcttct tcatggtccc tgcccagtcc tcgtggaact acaacttcat gggtgttcgg
     6961 catgacccca acatgaaata tgagctacag ctggcgaacc ccaaagagtt ctaccacgag
     7021 gtgcacaggc cctctcactt cctcaacttt gctctcctgc aggaggggga ggtttactct
     7081 gcggatcggg aggacctgta tgcctgaccg tttccctgcc tcctgcttca gcctcccgag
     7141 gccgaagcct cagcccctcc agacaggccg ctgacattca gcagtttggc ctctttccct
     7201 ctgtctgtgc ttgtgttgtt gacctcctga tggcttgtca tcctgaataa aatataataa
     7261 taaattttgt ataaatagga
//
