LOCUS       NM_001252078           14971 bp    mRNA    linear   PRI 03-SEP-2024
DEFINITION  Homo sapiens ubiquitin specific peptidase 15 (USP15), transcript
            variant 1, mRNA.
ACCESSION   NM_001252078
VERSION     NM_001252078.2
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 14971)
  AUTHORS   Yin,H., Wu,D., Qu,Q., Li,Z. and Zhao,L.
  TITLE     Ubiquitin-specific peptidase 15 regulates the TFAP4/PCGF1 axis
            facilitating liver metastasis of colorectal cancer and cell
            stemness
  JOURNAL   Biochem Pharmacol 226, 116319 (2024)
   PUBMED   38801926
  REMARK    GeneRIF: Ubiquitin-specific peptidase 15 regulates the TFAP4/PCGF1
            axis facilitating liver metastasis of colorectal cancer and cell
            stemness.
REFERENCE   2  (bases 1 to 14971)
  AUTHORS   Martinez,S., Wu,S., Geuenich,M., Malik,A., Weber,R., Woo,T.,
            Zhang,A., Jang,G.H., Dervovic,D., Al-Zahrani,K.N., Tsai,R.,
            Fodil,N., Gros,P., Gallinger,S., Neely,G.G., Notta,F., Sendoel,A.,
            Campbell,K., Elling,U. and Schramek,D.
  TITLE     In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of
            pancreatic cancer
  JOURNAL   Nat Commun 15 (1), 5266 (2024)
   PUBMED   38902237
  REMARK    GeneRIF: In vivo CRISPR screens reveal SCAF1 and USP15 as drivers
            of pancreatic cancer.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 14971)
  AUTHORS   Li,Y., Jiang,C., Liu,Q., Zhou,P., Tian,D., Zeng,Y. and Xiang,M.
  TITLE     USP15 facilitates the progression of bladder cancer by amplifying
            the activation of the NF-kappaB signaling pathway
  JOURNAL   Aging (Albany NY) 16 (8), 6757-6772 (2024)
   PUBMED   38656882
  REMARK    GeneRIF: USP15 facilitates the progression of bladder cancer by
            amplifying the activation of the NF-kappaB signaling pathway.
REFERENCE   4  (bases 1 to 14971)
  AUTHORS   Lu,X., Liu,R., Liao,Y., Cui,L., Sun,H., Zhang,D., Wang,B., Fang,L.,
            Guan,X., Yao,Y., Liu,C. and Zhang,Y.
  TITLE     ACVRL1 drives resistance to multitarget tyrosine kinase inhibitors
            in colorectal cancer by promoting USP15-mediated GPX2 stabilization
  JOURNAL   BMC Med 21 (1), 366 (2023)
   PUBMED   37743483
  REMARK    GeneRIF: ACVRL1 drives resistance to multitarget tyrosine kinase
            inhibitors in colorectal cancer by promoting USP15-mediated GPX2
            stabilization.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 14971)
  AUTHORS   de Carvalho,L.G.A., Komoto,T.T., Moreno,D.A., Goes,J.V.C., de
            Oliveira,R.T.G., de Lima Melo,M.M., Roa,M.E.G.V., Goncalves,P.G.,
            Montefusco-Pereira,C.V., Pinheiro,R.F. and Ribeiro Junior,H.L.
  TITLE     USP15-USP7 Axis and UBE2T Differential Expression May Predict
            Pathogenesis and Poor Prognosis in De Novo Myelodysplastic Neoplasm
  JOURNAL   Int J Mol Sci 24 (12), 10058 (2023)
   PUBMED   37373211
  REMARK    GeneRIF: USP15-USP7 Axis and UBE2T Differential Expression May
            Predict Pathogenesis and Poor Prognosis in De Novo Myelodysplastic
            Neoplasm.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 14971)
  AUTHORS   Vos,R.M., Altreuter,J., White,E.A. and Howley,P.M.
  TITLE     The ubiquitin-specific peptidase USP15 regulates human
            papillomavirus type 16 E6 protein stability
  JOURNAL   J Virol 83 (17), 8885-8892 (2009)
   PUBMED   19553310
  REMARK    GeneRIF: These results implicate USP15 directly in the regulation
            of E6 protein stability and suggest that ubiquitylated E6 could be
            a substrate for USP15 ubiquitin peptidase activity.
REFERENCE   7  (bases 1 to 14971)
  AUTHORS   de Jong,R.N., Ab,E., Diercks,T., Truffault,V., Daniels,M.,
            Kaptein,R. and Folkers,G.E.
  TITLE     Solution structure of the human ubiquitin-specific protease 15 DUSP
            domain
  JOURNAL   J Biol Chem 281 (8), 5026-5031 (2006)
   PUBMED   16298993
  REMARK    GeneRIF: analysis of the human ubiquitin-specific protease 15 DUSP
            domain
REFERENCE   8  (bases 1 to 14971)
  AUTHORS   Hetfeld,B.K., Helfrich,A., Kapelari,B., Scheel,H., Hofmann,K.,
            Guterman,A., Glickman,M., Schade,R., Kloetzel,P.M. and Dubiel,W.
  TITLE     The zinc finger of the CSN-associated deubiquitinating enzyme USP15
            is essential to rescue the E3 ligase Rbx1
  JOURNAL   Curr Biol 15 (13), 1217-1221 (2005)
   PUBMED   16005295
  REMARK    GeneRIF: A functional Zn finger of USP15 is needed to maintain a
            conformation essential for disassembling poly-Ub chains, a
            prerequisite for rescuing the E3 ligase Rbx1.
REFERENCE   9  (bases 1 to 14971)
  AUTHORS   Baker,R.T., Wang,X.W., Woollatt,E., White,J.A. and Sutherland,G.R.
  TITLE     Identification, functional characterization, and chromosomal
            localization of USP15, a novel human ubiquitin-specific protease
            related to the UNP oncoprotein, and a systematic nomenclature for
            human ubiquitin-specific proteases
  JOURNAL   Genomics 59 (3), 264-274 (1999)
   PUBMED   10444327
REFERENCE   10 (bases 1 to 14971)
  AUTHORS   D'Andrea,A. and Pellman,D.
  TITLE     Deubiquitinating enzymes: a new class of biological regulators
  JOURNAL   Crit Rev Biochem Mol Biol 33 (5), 337-352 (1998)
   PUBMED   9827704
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF153604.1 and AC079035.46.
            
            On Nov 23, 2018 this sequence version replaced NM_001252078.1.
            
            Summary: This gene encodes a member of the ubiquitin specific
            protease (USP) family of deubiquitinating enzymes. USP enzymes play
            critical roles in ubiquitin-dependent processes through
            polyubiquitin chain disassembly and hydrolysis of
            ubiquitin-substrate bonds. The encoded protein associates with the
            COP9 signalosome, and also plays a role in transforming growth
            factor beta signalling through deubiquitination of
            receptor-activated SMAD transcription factors. Alternatively
            spliced transcript variants encoding multiple isoforms have been
            observed for this gene, and a pseudogene of this gene is located on
            the long arm of chromosome 2. [provided by RefSeq, Nov 2011].
            
            Transcript Variant: This variant (1) 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. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: SRR1660807.243739.1,
                                           SRR1660805.110176.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000280377.10/ ENSP00000280377.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1465              AF153604.1         47-1511
            1466-1466           AC079035.46        83641-83641
            1467-3224           AF153604.1         1513-3270
            3225-14971          AC079035.46        103999-115745
FEATURES             Location/Qualifiers
     source          1..14971
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q14.1"
     gene            1..14971
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /note="ubiquitin specific peptidase 15"
                     /db_xref="GeneID:9958"
                     /db_xref="HGNC:HGNC:12613"
                     /db_xref="MIM:604731"
     exon            1..100
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     CDS             12..2957
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /EC_number="3.4.19.12"
                     /note="isoform 1 is encoded by transcript variant 1;
                     ubiquitin carboxyl-terminal hydrolase 15; ubiquitin
                     thioesterase 15; deubiquitinating enzyme 15;
                     ubiquitin-specific-processing protease 15; ubiquitin
                     thiolesterase 15"
                     /codon_start=1
                     /product="ubiquitin carboxyl-terminal hydrolase 15 isoform
                     1"
                     /protein_id="NP_001239007.1"
                     /db_xref="CCDS:CCDS58251.1"
                     /db_xref="GeneID:9958"
                     /db_xref="HGNC:HGNC:12613"
                     /db_xref="MIM:604731"
                     /translation="MAEGGAADLDTQRSDIATLLKTSLRKGDTWYLVDSRWFKQWKKY
                     VGFDSWDKYQMGDQNVYPGPIDNSGLLKDGDAQSLKEHLIDELDYILLPTEGWNKLVS
                     WYTLMEGQEPIARKVVEQGMFVKHCKVEVYLTELKLCENGNMNNVVTRRFSKADTIDT
                     IEKEIRKIFSIPDEKETRLWNKYMSNTFEPLNKPDSTIQDAGLYQGQVLVIEQKNEDG
                     TWPRGPSTPKSPGASNFSTLPKISPSSLSNNYNNMNNRNVKNSNYCLPSYTAYKNYDY
                     SEPGRNNEQPGLCGLSNLGNTCFMNSAIQCLSNTPPLTEYFLNDKYQEELNFDNPLGM
                     RGEIAKSYAELIKQMWSGKFSYVTPRAFKTQVGRFAPQFSGYQQQDCQELLAFLLDGL
                     HEDLNRIRKKPYIQLKDADGRPDKVVAEEAWENHLKRNDSIIVDIFHGLFKSTLVCPE
                     CAKISVTFDPFCYLTLPLPMKKERTLEVYLVRMDPLTKPMQYKVVVPKIGNILDLCTA
                     LSALSGIPADKMIVTDIYNHRFHRIFAMDENLSSIMERDDIYVFEININRTEDTEHVI
                     IPVCLREKFRHSSYTHHTGSSLFGQPFLMAVPRNNTEDKLYNLLLLRMCRYVKISTET
                     EETEGSLHCCKDQNINGNGPNGIHEEGSPSEMETDEPDDESSQDQELPSENENSQSED
                     SVGGDNDSENGLCTEDTCKGQLTGHKKRLFTFQFNNLGNTDINYIKDDTRHIRFDDRQ
                     LRLDERSFLALDWDPDLKKRYFDENAAEDFEKHESVEYKPPKKPFVKLKDCIELFTTK
                     EKLGAEDPWYCPNCKEHQQATKKLDLWSLPPVLVVHLKRFSYSRYMRDKLDTLVDFPI
                     NDLDMSEFLINPNAGPCRYNLIAVSNHYGGMGGGHYTAFAKNKDDGKWYYFDDSSVST
                     ASEDQIVSKAAYVLFYQRQDTFSGTGFFPLDRETKGASAATGIPLESDEDSNDNDNDI
                     ENENCMHTN"
     exon            101..228
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            229..359
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            360..486
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            487..632
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            633..694
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            695..781
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            782..926
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            927..1100
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            1101..1259
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            1260..1484
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            1485..1568
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            1569..1663
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            1664..1855
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            1856..1971
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            1972..2244
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            2245..2315
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            2316..2431
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            2432..2581
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            2582..2685
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            2686..2774
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            2775..14971
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3205..3210
                     /regulatory_class="polyA_signal_sequence"
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /note="hexamer: AATAAA"
     polyA_site      3225
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /note="major polyA site"
     regulatory      4680..4685
                     /regulatory_class="polyA_signal_sequence"
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /note="hexamer: AATAAA"
     polyA_site      4701
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
     regulatory      8282..8287
                     /regulatory_class="polyA_signal_sequence"
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /note="hexamer: AATAAA"
     polyA_site      8303
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
     polyA_site      13604
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
     regulatory      14952..14957
                     /regulatory_class="polyA_signal_sequence"
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
                     /note="hexamer: ATTAAA"
     polyA_site      14971
                     /gene="USP15"
                     /gene_synonym="UNPH-2; UNPH4"
ORIGIN      
        1 agtggaagaa gatggcggaa ggcggagcgg cggatctgga cacccagcgg tctgacatcg
       61 cgacgctgct caaaacctcg ctccggaaag gggacacctg gtacctagtc gatagtcgct
      121 ggttcaaaca gtggaaaaaa tatgttggct ttgacagttg ggacaaatac cagatgggag
      181 atcaaaatgt gtatcctgga cccattgata actctggact tctcaaagat ggtgatgccc
      241 agtcacttaa ggaacacctt attgatgaat tggattacat actgttgcca actgaaggtt
      301 ggaataaact tgtcagctgg tacacattga tggaaggtca agagccaata gcacgaaagg
      361 tggttgaaca gggtatgttt gtaaagcact gcaaagtaga agtatatctc acagaattga
      421 agctatgtga aaatggaaac atgaataatg ttgtaactcg aagatttagc aaagctgaca
      481 caatagatac aattgaaaag gaaataagaa aaatcttcag tattccagat gaaaaggaga
      541 ccagattgtg gaacaaatac atgagtaaca catttgaacc actgaataaa ccagacagca
      601 ccattcagga tgctggttta taccaaggac aggtattagt gatagaacag aaaaatgaag
      661 atggaacatg gccaaggggt ccttctactc ctaagtcccc aggtgcatcc aatttttcaa
      721 ctttaccaaa gatctctcct tcatctctat caaataatta taacaacatg aacaacagaa
      781 atgtgaaaaa ctcaaattac tgtcttccat catataccgc ttataagaac tatgattatt
      841 cggaacctgg aagaaacaat gaacagccag gcctctgtgg cctaagtaac ttgggaaata
      901 cgtgtttcat gaactcagct attcagtgtt tgagcaacac acctccactt actgagtatt
      961 tcctcaatga taagtatcaa gaagaactga attttgacaa tcccttagga atgagaggtg
     1021 aaatagctaa atcttatgcc gaactgatca agcaaatgtg gtctggaaag tttagctacg
     1081 tcaccccaag agcctttaag acacaggtag gacgttttgc acctcagttc tctggatatc
     1141 agcagcaaga ctgtcaagaa ctgttagctt tcctattaga tggattacat gaggatttga
     1201 atagaattag gaaaaaacca tatatacaat taaaagatgc agatggaagg ccagataagg
     1261 tggttgccga agaagcctgg gaaaaccatt taaaacgaaa tgattctatc atagtagata
     1321 tatttcatgg ccttttcaaa tcaactttag tttgtcctga gtgtgctaag atttcagtaa
     1381 catttgatcc tttttgttac ttgacacttc cattgcccat gaaaaaagaa cgcaccttgg
     1441 aagtttactt agttagaatg gatccactta ccaaacctat gcagtacaaa gtggttgtcc
     1501 ccaaaattgg aaacatatta gatctttgta cagcattgtc tgctttgtca ggaatacctg
     1561 cagataagat gatagttact gatatataca atcatagatt tcacagaata ttcgctatgg
     1621 atgaaaacct tagtagtatt atggaacggg atgatattta tgtgtttgaa attaacatca
     1681 ataggacaga agatacagag cacgtgatta ttcctgtttg cctaagagaa aaattcagac
     1741 actcgagtta tacccaccat actggttctt cactttttgg tcagcccttt cttatggctg
     1801 taccacgaaa caatactgaa gacaaacttt ataatctcct gctcttgaga atgtgccgat
     1861 atgtcaaaat atctactgaa actgaagaaa ctgaaggatc cctacactgc tgtaaggacc
     1921 aaaatattaa tgggaatggc ccaaatggca tacatgaaga aggctcacca agtgaaatgg
     1981 aaacagatga gccagatgat gaatccagcc aggatcaaga acttccctca gagaatgaaa
     2041 acagtcagtc tgaagattca gttggaggag ataatgattc tgaaaatgga ttatgtactg
     2101 aggatacttg caaaggtcaa ctcacgggac acaaaaaacg attgtttaca ttccagttca
     2161 acaacttagg caatactgat atcaactaca tcaaagatga taccaggcat ataagatttg
     2221 atgataggca gcttaggcta gatgaaagat cttttcttgc tttggattgg gatcctgatt
     2281 tgaaaaaaag atattttgat gaaaatgctg ctgaggactt tgaaaaacat gaaagtgtgg
     2341 agtataaacc tcctaaaaaa ccctttgtga aattaaaaga ttgcattgaa ctttttacaa
     2401 caaaagaaaa gctaggtgct gaagatccct ggtattgtcc gaattgtaaa gaacatcagc
     2461 aagccacaaa gaaattggat ttatggtccc tgcctccagt acttgtagta catctcaagc
     2521 gattttctta cagtcgatac atgagagaca agttggatac cttagttgat tttcctatca
     2581 atgacttgga tatgtcggaa ttcttaatta atccaaatgc aggtccttgc cgctataatc
     2641 tgattgctgt ttccaaccac tatggaggga tgggaggagg acactatact gcttttgcaa
     2701 aaaataaaga tgatggaaaa tggtactatt ttgatgacag tagtgtctcc actgcatctg
     2761 aagaccaaat tgtgtccaaa gcagcatatg tactcttcta ccagagacaa gacactttca
     2821 gtggaactgg cttttttcct cttgaccgag aaactaaagg tgcttcagct gccactggca
     2881 tcccattaga aagtgatgaa gatagcaatg ataatgacaa tgatatagaa aatgaaaact
     2941 gtatgcacac taactaatga aagtcctaga agccataaaa gagacacttt cctgctggtg
     3001 gtatctatgg aaatgatgaa gttacccacc acattaaaac aaaagtctga gatggggagt
     3061 ttcagataac cgaatgtaaa tcctttatca gattttaact tgtgcagtac ttgaagtgaa
     3121 acacaatgaa aactttaaca gaaattgtct cttaatacat ttacagtctt gtatttacaa
     3181 gctaaatata tataggaaat cacaaataaa tcccttttaa gtttgctgct gttttgatta
     3241 attatgtttc ctttaatttt ttggatgtga gttgatgaca aatgttaaat ttgtggatgt
     3301 tggtcattta ttttgctcta ataatactgc aagaaaacta tggctgaact tagtttttgg
     3361 ataatctagt tcatgtgcat taggctgccg tatatactac tatgatattt agctgcagta
     3421 tcaatgtggc ataaatactg cggcagcatt cttcgaaaac cgcattttca aatttatccc
     3481 cgtaatcaat gtgggcctat taaaaaacca aatcatgata caagaaacaa ccttggaaaa
     3541 gttatttccc tttgtaatac ctttaaaaat ccagagtatt atattcattt tactgccact
     3601 gtggaaacag gttctagatt tcatactcca tctaaagtca tttttcagtt acatgtaagt
     3661 attatttact gctattggga tctattcttc agatattcaa aaacattttt tgctttaaaa
     3721 tgcatatctt taattgggtg ttggtccaaa attaaaattt ttgctgtctg tttttctcta
     3781 ccccattttg tggtaatttg gcaacttgag ctctcccaat tattgtaata taaggacaga
     3841 cataatagta ttctgtaccc atagtaataa ttgcatcaag cttagatgag aaattttttt
     3901 catatactgg cctttaaatc attaatggac aattggctat aaaggtaggt ctgttaactt
     3961 tctttgtgtg ttcctgatgg aattcaccat agccttacag cttttctcag aaggtaactt
     4021 gttataagag aaatggcatt tgcatgttcc agagtcagaa cctgtacagt atataaagca
     4081 taaacacctt gaatttgatt ttagttcacc acattcaagg atccaggatg ccaaaaatat
     4141 gtgtgaacat ttgaaacatt tttatttgct gctttttccc tttgatatag ttgaaagaat
     4201 gtattgtaaa ttggcataca atactgcctt taatagaaaa cctaaatgct ggggcacatt
     4261 tcacatatcg actacctgag aaattgcttt gtgtcccact gttattaaag caaaaagtat
     4321 aatgttcttc acttgaacta atcaaataca atagattata aattgtgtat tgtaaataaa
     4381 agttcactct gtgagtgcac attttggtaa attatttatt tatgttagca tttaaaagtt
     4441 taaaaaaaat gcatttgacc aggataaatg aggtatgttg atcatggctt tgctttatat
     4501 cttgatatta aagctggttt atcatcctgg tattttaaaa gctgctttgg ggtttttttt
     4561 ttcttttttt tttttttaat gtaaactaac ctcctgcatg acagaggtta aaattttgtc
     4621 tgcacttgag ttcacttgag tttacatttg aaatgtgcat gtttatttat atagatttca
     4681 ataaagctat tcaaggcctt atttagtctt ttatttctta ctcttaatct tttaataaaa
     4741 atcccctact ttatggttag atgactatat gctagacttt ttagttataa atagttaata
     4801 ctagaaagga aattatgtca gagcaaaatg aatcctacta ttaaggacgt tttaaagttg
     4861 atttttgtcc actttaatat ttattcatta aacatatgtt tgtgtaccaa tcactgttgt
     4921 agagtctgga gatacagcag taaacaaata tccttacctt cacagagctt acattctttc
     4981 tgccatctac caactaatga actatatttc catttttctg aagatttaaa gaaaagtcaa
     5041 agctaaatct tttaaaccta tattgtggtc tccatcctaa ttcttcagag accactttct
     5101 ttttaatgcc tgtcattaac ttctgttccc actaaaagaa gtgatgttaa taatgccatt
     5161 gaaactgcca aactcaaatg tcatttttca gctgcaagaa gtatacttta aaaatagtgc
     5221 aaaaggataa tacatattct aattaaaagt aggcattcag actgggcacg gtggttcatg
     5281 cctgtaatcc cagcactttg ggagactcag gcgggaggat cacttgagcc caggagtttg
     5341 agaccagcct gagtaacata gtgagaacct catctgtaca aatatatgta ttttttttta
     5401 attagctggg tgtgcacaca cctgtgttcc cagctactgg ggaggctgag gtgagagaat
     5461 tgcttgagcc caggcagtca aggccgcagt tagccgaaat cacacccctg cactccagcc
     5521 tgtgcaacat agcaagactc tgtctcaaaa aaaaaaaaga tattcatagg taatacaggg
     5581 taatgggaat atatctagac tagaatttct acttctagct ttgccactta gcaatcatat
     5641 gactttgaac ttaatctttg atagtgtttc tttacctgta gaataatgat gataatagcc
     5701 agcatttatt gagcacttac tatggaccag gcactatatt aaagtgttta tatgcattct
     5761 ctcatttaat cccacaacag ctatgaggta gggatagttg tcatccccat ttttcatatg
     5821 aagaaaccaa gatacaaagc atttaagtaa tattcccaag ctcacacaat tgctatgggg
     5881 tagagccaat attctatcct cagatatata ctacctctca ctgtgttata gtgtctgcct
     5941 cataggattg ttgagagctc aaatgagatc atgtatttta tgggaagagc tttgtaaact
     6001 ttattacaca ctcactgatt tcttcagtct aaatagaaag acatcttgaa gtctaataac
     6061 tttgcttcta aaagtatatt tagctcagta ttcgagcatt gaataagaaa gtacccactg
     6121 gaatattgac taacccattc ccttttaaaa attaatttca tttaatttat atacctttat
     6181 tacaatttta attaaatggt aaatacaatg tgacattttt ttcttacctt ttcatctaac
     6241 ttgtgtcccc ttctttccat ttccccaaat gcaaccctga atttcaggac tttgtaaact
     6301 ctactctagt tttgctttct gtttgtttgt ttgtttgttt agagacaagg tctccctctg
     6361 tcgcccaggc tggagtgcag tgacataatc atagttcact gtaaccttga actcctgggt
     6421 taaagtgatc ctcctgcctc agccttataa tttagtttta attaacctcc ttgaaaaagt
     6481 tgcagcctgg tgctttattt aaatatcttg ctttctcata atctgtgtta ttttagtagt
     6541 cctgtattta tccttgcttt cctgacaact ggatataaaa ctacacaaaa cattgatttg
     6601 ggcacaaaga aaatcagtaa gtaccaaaat agatacaaca taaaggtggt ggggtttttt
     6661 atgaactaat ttgattgaag tgagtttatc ttataaaata agccgggaga ctgaaatgga
     6721 gtctccttca gtggtacacc aaagggagtg tagggtgtag taggagctct ctgcctccga
     6781 gaggaggaat atattagact gataacgttt aagtctgatg tatggtgaca agaaaaaggc
     6841 caattttttg ttttgttatt tttaagttac ctacagataa tgcatttcat tattgcctac
     6901 ttccaactct ccctatgtag tatgtttctg atcttctgtg cttgtgcagt gtagatgagc
     6961 tcaccgcttt aatttttaag atagaaatgt ggaaaactct tgaatcatag actaggggaa
     7021 ggaaccagag gtcctctaaa atatcagagg agtgagaagg aaaggaagag ctcctttcta
     7081 gggccataga ataagagtag aagtttttgc tcattttttt tgtttgtttt tactttacaa
     7141 aaaaataaaa aattttttgc tctttgaata acttaacatg aggaatttgg aaacaacctc
     7201 tcttgaaaat atattggtat tcattcccaa ataattcttc taagtaccac ttgaccagag
     7261 gatagggaaa ggaggaaaag gtgagtgtat ttatatcctt gctagttttt gttatatatt
     7321 cagttgcaga tctatattat atatcatttt attatcagat tttctagtga gaaatatata
     7381 tgatggtttt ttaataatca ttttaggttt ggaggccatt tcaattcaat atgtatgtgt
     7441 tttacgtgtt taattcgtat ttactatata ttaaaagaat ttccaaatag ctcagataag
     7501 aaaactttgg tttaaaattg agttatttta taagctacat agaatacatc aaaattttat
     7561 aagctgcata gaataggctt taaaatatca gaattaggaa aataaaatat agatggtaaa
     7621 aattcaaata tttatcaaga cttttttctt cactaatgat ggggtaaaga atttttaaat
     7681 ggataatata aaacagacag ttcaaaaatt atttttggaa aatatatgca tcgggaaaca
     7741 taccccacac ggtgccatgg tttaattatt ccccagctct acttttggga gcctggaact
     7801 tgtcagggtt gtgaaataga tctcagacta ttaaggacat tcagaaactg gctaagccat
     7861 tcaaggaaaa tcaggaattt acgtaatata ttggactaca gtctcaaagg acagagagaa
     7921 aatcagtcaa atgggttttg atattttttt ttcctagaaa tgtgtagcaa atgtgatttt
     7981 acaaagcagc taaaaataca actatctctc tggaattgaa aatgtgtaaa ataagaccac
     8041 acactttcaa tatgcacaaa atatatttta aatgtttaag ttgtattggt aatttactat
     8101 gttctcctgt agaaaatcat aattaaagtt ggtgctcgtg ttgctaaagt tttttttctc
     8161 atgtcaggaa cttgcagctt gttctatata gtttggtgaa acaaacaaaa cagtttttat
     8221 ctgctgtgac atttaagttt gttgttagct ggagttaaat ctacatacat aaaagtaaaa
     8281 caataaatat ggaaacatcc caacagtctt tcccacaatg tgtattatta cattattctc
     8341 agtaatgaca catacttaac atttcccaag ctgttgtttt aaaccttaaa catcaccaca
     8401 tttctaattt ttatttaaaa tctttcagaa ttcttagatt ttgtaacata tcaagcacaa
     8461 gtctctcatt aaaatttttt tttaatagta tttgcttttc ttttaaactc cataaaggag
     8521 tattcgatgt taacagacgt aactctttaa tgctcctctg ttcatgatta agtatgctaa
     8581 gttttaagta atttagacta atgtattaaa gtgttcactt atgtctagtc atatgcatac
     8641 ctactctctt ctaaccttga gtcatttcta ttaaatacag catttaatct tctttcaagt
     8701 gagaaccatc tttccattat atcaagtggg caatatttaa attgtctgat aagttcatcc
     8761 aaattaatcc catcatgcct gtttaactca tttccccaaa aagaccgcga cctccagcca
     8821 gtcattcagt tcttgaactc cctaatagaa gcaccaagga ttatctattt gtaatcacat
     8881 tgtggtgaat tatcagtctc ccaagaatta tgtaaagcaa ataggaatta ttttagagtt
     8941 gcccttattt taaaaaacaa aaaaaaagta aagatgggaa aattacttat agtatttttt
     9001 tttaatttga gaaagaattc ctgtaggtct cccttaaata gtgactttgg taaagctttt
     9061 taatttctag aactcagagc tatattcact tttgagctat gtacctattg tataagttga
     9121 agtaatactg caaattcaaa cagtaaacat cattaatcct agatatttgg gtactaccta
     9181 cagtgagata tggtaggaaa cattctacac ttacaacaac ttccaccata gctagctcca
     9241 aacaggtcat taacctctga attactgttt tcacaaccat aaaattatgc tggtctcttg
     9301 aaagtattag tttatgggtg tggagaggaa ggcttaaatt tcatttttga agctgtcgtt
     9361 aaaagtatat atttttagca aaggaattaa taactaatag cattgatgag tcaagttaat
     9421 atttgttttt gttttttttt ttttttaatt ttgggcctca ctcctataaa agacttggaa
     9481 cagaagtctt agtatgatgg taaacttgaa aattaaaatt ttatcaggga tattagaatc
     9541 caattatatg agactgcatc ctcaacaggc accttggttg caacaccatg aaagaccttg
     9601 atccagaggt tctcagcaag ccacacctga attcctaacc cacaaaaact gtgagataac
     9661 agatgtttgt gtttttagct gctaagcttt aatttgttta tgcagaaata agggaaaagg
     9721 accctagaga tccttgagga atcccacttt acagatgtag aagctgaggg ctagaaggag
     9781 aaaagtcatg tacacaaagt ctggagacaa ctcagatagt cactacatcc tcttgctctt
     9841 tctcattttt actctttaac tggctcctca ctttttagat ggatggcact gggctctgga
     9901 gcaaaccatc tgttctgtat ctgttaaggc ctctagagct tcattcattc cttcatcaaa
     9961 tattttttga gtgtccacta tgtgccaggc actattctag attcaagata taaagtaata
    10021 tacaaaaaca aaatccagtt acaaatataa tttttaaagc tatttgtgag cataacttcg
    10081 taacacattt agaacctttg ccttcagctg acatgaatta tgttgtcttt ttgttttttg
    10141 gtccagtttc attagtcatt aaagtcattt gaattaaaga caataatcca gactccagag
    10201 gttatggctt ttatgtgttt ggatactgtc atagtctgct caggctgcca taacaaacac
    10261 agactgggtg gcttaaataa cagaaattta tattttcaca gttctggagg ctgggaatct
    10321 gagatcaggg taccagtata ctgggtttct ggtgagggtg cctttcctgg cttacagatg
    10381 gctgccttct cactgtgttc ttgcatggta gcagaggagg gtcagagagg agagcaagct
    10441 ctgaggcatc tcttttttat aagggcacta atcccgtcat gaagccctca ccctcatgac
    10501 ctcatctaaa cctaattatc tcctaaagac ttcctctcca aatactattt aaggcttcaa
    10561 cctgaatttg gaggtgacac agttgagccc atagcagata tatttagtaa caactgtggg
    10621 tacaggcatg cctcagatat tgcaggttcg gttcccagcc accataaata tttaaataaa
    10681 gtgagtcaca aattttttgg tttcccagtg catataaaag gcatatttac cctatactgt
    10741 agtctattaa ctgcaataac attgtgccta aaaaagatgt acatgcctta attttcaaac
    10801 tattgccaaa aaatgctaaa taaccatcag agccttcagc aagtagtaat gtttttgctg
    10861 atggacagtc ttgcctcatt ttgatagata ctcaccagga tggtggttgc tgaaggttag
    10921 ggtggccgtg gcaatttttt acaataagac agtagtgaag tttgcttcat caattgactc
    10981 ttccttttac aagagatttc tctggcatgc agtgctattt gataatattt gatacccaca
    11041 gtagaacttc tttccgaact tctttcacaa ttggagttaa tcttctaaag ccccgccact
    11101 gcttcatcaa ctaagtttat ggaatattct aaatcctttg ttgtcttttc aacaatgttc
    11161 acagcatctt caccaggaga agactttccc cccttctttt cacagatgtt gagattgtca
    11221 agaaactact ttccttgccc acccataaga agcaacttat catctgttca agttttatca
    11281 taagattgca gcaatccaga cacatcttca ggctccactt gtagttctct tgctattttc
    11341 accgcatctg cagttactgc cgccactgag gttttgaact tctcaaagtc atgaaagttg
    11401 taattaactt ctttcaaact cttgttaatg ttgatatttt gactcccatg aatcacaaat
    11461 attctgaatg aatggcatcc agaatagcaa atccttttca gaaggttttt attttgccca
    11521 gatccatcag aggaatcact atctatgaaa gcttttgcct tataaaatgt atttcttgga
    11581 tgataagact tgaaagctga agttattctt tgatctatgg ctgcagaatg gatgttgtgt
    11641 tagcaggcag aaaaacacta atctcataca tctccataga gctcttgggt gaccaggtgc
    11701 acttgtcaat gagcagtaat attttgaaag gaatcttttt ctgagcaata gatctccgca
    11761 gtgggcttaa aatatttagt aaaccttcct ataaacggat gtgctaccat ccaggcttta
    11821 tggttccttt tatagagcaa aaacattata tttagtttaa ttttaaggac cctaggattt
    11881 ttggaatgat aaatgaacat tagttagcat tgcattggcc cctaacaaga aatcagtctc
    11941 tcgtttgaag ccaagcatca acttttctct agctatgaaa gtcctggatg acatcttcca
    12001 acataagact ttcatctaca ttgaaagttt gtttttagtg taactacctt catcaatgat
    12061 cttagctaga tcttctggat aacttgctgt agtttctact ttagcagttg ctgcttcacc
    12121 ttatgcttgt ctgttgtgga gacagcttgt ttccttaaac tccatgaatc aaccactgct
    12181 agcttcagac ttttcttctg cagcttcctt accttagcct ccatagaatt gaagagagag
    12241 ggccttgctc tgcgttaggc tttggcttaa gatagtgttg tggctgattt gatctattaa
    12301 aaaaaaaaaa actcaggctt tctctatacc acttttctta tgattcatgt gttcacttga
    12361 gtagcacttt taatttcagg aactcttcct ttggatatac aacttggctg tttggctcaa
    12421 gaggcctagc tttcagcttg ccttggcttt caacatgctt tcctcactaa gctccaatca
    12481 tttatagcat ttgattgaga gagagagaga gatgtacagc tcttcacctg aacatttaga
    12541 ggccattgga tggttattaa ctggcctggt tttaatagtg ttatgtctca gggaataggg
    12601 aggcacatgg agagggagag agatggggaa tggccagtgg agcagttgga acacacacgt
    12661 ctgtgccctc aaacaaaaca gtaacatcaa agattactga tcacagatca ccgtaacaga
    12721 tacaataata atgaagacat ttgaaatgtg agaagtacca agatatgaca cacacacagt
    12781 aagcacattc tgttaggaaa ataacaccta tagatgtgct caatgtaggc ttgccacaag
    12841 ccttgtttgt aaaaaaacaa aaacaattat cttcaaagca tgataataaa gtgaagcaga
    12901 ataaaacaag gtatgcctgg tttttgtttt gttttgtttt gagacaaggt ctttctctgt
    12961 cacccaggct ggagtgcagt ggcacaatct catctcactg cagcctccag cctctgggct
    13021 caagtggtcc tcccacctca gcctccgaag tagctgggtc tacaggcatg tgccaccaca
    13081 ccacacctgg ctaatttttg tagagaccag gtttcaccat gttacccagg ctggttttga
    13141 agtcttgaac tcaggcgatc catccacctc ggcctcccaa agtgctggga ttacaggcat
    13201 gaaccacagc acctggccat gtattttcat ttaaccagta ctaaataact acatgtcttt
    13261 ggcagcctat aatgtagcat cccattttta aaaatagaag tgtgtattca gggtgcactc
    13321 aataggatta catctggctg gcagtccctt cctacttcag tccattatcc tgctaccaga
    13381 atgatcttca tggtttcatt taaaaaaaaa aaaaatgaga tcctgtttct gtcttaaagt
    13441 tctcttctaa ttccttgtat taatcaggat tctccagaga aacaagacca ataggatgca
    13501 tatgtgtata cacatatatg tatagctctc tccctcatat atacacatat catgtatata
    13561 catatatatc atatatgtac atatatatat atatatatga gggagagaaa gatttataag
    13621 gaattagttc atgcacttag gctgagaagt ctcatgatct tcagtcagca ggctggagac
    13681 ccaggaatgc caatggtgta gttcaagtcc gagtccaaag ggttgagaac caggaaaacc
    13741 aatgataaaa gttccagtcc acaagctacc tggctaaaga cccaggaaga ctgaatgttt
    13801 cagttttagt gcaaaggcag gaaaagactg atgtcccagt tcaatcaggc aagagaaatt
    13861 atccttactt gagccttttt tgttctattc aggccttcaa ttcatgagag ccaccaacat
    13921 tagagagggc aatctgcctt actcagtcta ctgacttaaa tgttaatctc atccaaaaac
    13981 accctcatag atatgcccag aataatgttt gaccacatat ctgggcaccc tgtggcccag
    14041 tcaacacatt aaataaacca tcacatccct tcatgtagaa aagagtggtt tggaccatag
    14101 gctcaggagt taaaccacct ctgagcctac cacttttgtg caactcacct cacctctctg
    14161 cctttcacct ctctgtaaac tagagcagct cccgaatgtc catctaggaa ggcttggggt
    14221 gagcaacctg attagaaggg aacaatgtga cttaaaactg catatttgct tagcaaacct
    14281 atgacttttc tcagaatata cagtttgctt gtgatggagg gctattaata tttataagga
    14341 aaccaaatcc ccattcactt aagccatcca ctcctaccac tgtaattgaa tattacctac
    14401 ctttcagaat aattgcaagg ttttgtgtct tgatcattat gaaaaatgtg gcaggtatta
    14461 ttactaataa agaagtaccc aactatggga atgattgttc cttccttatg aatgagagca
    14521 gctctctgtt caatacgatt catactcaag ttctaataaa ctttctttag caagagagca
    14581 aagagtatgg tacagtcagt ccacccaggt tgcctgttaa cctggtgctt gaaggaaaaa
    14641 aagtaagaat ttgccctcat ctaattcctc acttgccctc aaacatgtca tactacttga
    14701 caatggggct ttcccacatt tgtcccacat ttgcatggtc tgccttatct cttacctggc
    14761 gaactcctac actccttcaa gacttgctcc aaaatgcact tgctagatct tctgacatca
    14821 actgccacct tgggctataa gttacgtgtg tctcttcccc cactagacaa ttacctgatg
    14881 gaagaatatt gttcttaaga tgttaagatg gtgtatgtgt ggcatagtat ttgttcctaa
    14941 atgtaaaagt tattaaacaa gttttctgaa a
//
