LOCUS       NM_001346413            6270 bp    mRNA    linear   PRI 22-SEP-2024
DEFINITION  Homo sapiens PCF11 cleavage and polyadenylation factor subunit
            (PCF11), transcript variant 1, mRNA.
ACCESSION   NM_001346413 XM_005274048
VERSION     NM_001346413.3
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 6270)
  AUTHORS   Boreikaite,V., Elliott,T.S., Chin,J.W. and Passmore,L.A.
  TITLE     RBBP6 activates the pre-mRNA 3' end processing machinery in humans
  JOURNAL   Genes Dev 36 (3-4), 210-224 (2022)
   PUBMED   35177536
REFERENCE   2  (bases 1 to 6270)
  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   3  (bases 1 to 6270)
  AUTHORS   Kamieniarz-Gdula,K., Gdula,M.R., Panser,K., Nojima,T., Monks,J.,
            Wisniewski,J.R., Riepsaame,J., Brockdorff,N., Pauli,A. and
            Proudfoot,N.J.
  TITLE     Selective Roles of Vertebrate PCF11 in Premature and Full-Length
            Transcript Termination
  JOURNAL   Mol Cell 74 (1), 158-172 (2019)
   PUBMED   30819644
  REMARK    GeneRIF: PCF11 selectively attenuates the expression of other
            transcriptional regulators by premature cleavage/polyadenylation
            and termination.
REFERENCE   4  (bases 1 to 6270)
  AUTHORS   Wang,R., Zheng,D., Wei,L., Ding,Q. and Tian,B.
  TITLE     Regulation of Intronic Polyadenylation by PCF11 Impacts mRNA
            Expression of Long Genes
  JOURNAL   Cell Rep 26 (10), 2766-2778 (2019)
   PUBMED   30840896
  REMARK    GeneRIF: PCF11 is autoregulated through a conserved IPA site, the
            removal of which leads to global activation of PASs close to gene
            promotors. Therefore, PCF11 uses distinct mechanisms to regulate
            genes of different sizes, and its autoregulation maintains
            homeostasis of PAS usage in the cell.
REFERENCE   5  (bases 1 to 6270)
  AUTHORS   Ogorodnikov,A., Levin,M., Tattikota,S., Tokalov,S., Hoque,M.,
            Scherzinger,D., Marini,F., Poetsch,A., Binder,H.,
            Macher-Goppinger,S., Probst,H.C., Tian,B., Schaefer,M.,
            Lackner,K.J., Westermann,F. and Danckwardt,S.
  TITLE     Transcriptome 3'end organization by PCF11 links alternative
            polyadenylation to formation and neuronal differentiation of
            neuroblastoma
  JOURNAL   Nat Commun 9 (1), 5331 (2018)
   PUBMED   30552333
  REMARK    GeneRIF: Utilising extensive RNAi-screening authors reveal the
            landscape and drivers of transcriptome 3'end-diversification,
            discovering PCF11 as critical regulator, directing alternative
            polyadenylation (APA) of hundreds of transcripts including a
            differentiation RNA-operon.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 6270)
  AUTHORS   Schafer,P., Tuting,C., Schonemann,L., Kuhn,U., Treiber,T.,
            Treiber,N., Ihling,C., Graber,A., Keller,W., Meister,G., Sinz,A.
            and Wahle,E.
  TITLE     Reconstitution of mammalian cleavage factor II involved in 3'
            processing of mRNA precursors
  JOURNAL   RNA 24 (12), 1721-1737 (2018)
   PUBMED   30139799
  REMARK    GeneRIF: We have reconstituted CF II as a heterodimer of hPcf11 and
            hClp1. The heterodimer is active in partially reconstituted
            cleavage reactions, whereas hClp1 by itself is not. Pcf11
            moderately stimulates the RNA 5' kinase activity of hClp1; the
            kinase activity is dispensable for RNA cleavage
REFERENCE   7  (bases 1 to 6270)
  AUTHORS   Volanakis,A., Kamieniarz-Gdula,K., Schlackow,M. and Proudfoot,N.J.
  TITLE     WNK1 kinase and the termination factor PCF11 connect nuclear mRNA
            export with transcription
  JOURNAL   Genes Dev 31 (21), 2175-2185 (2017)
   PUBMED   29196535
  REMARK    GeneRIF: WNK1 and the associated phosphorylation of the PCF11 CID
            act to promote transcript release from chromatin-associated Pol II,
            which in turn facilitates mRNA export to the cytoplasm
REFERENCE   8  (bases 1 to 6270)
  AUTHORS   West,S. and Proudfoot,N.J.
  TITLE     Human Pcf11 enhances degradation of RNA polymerase II-associated
            nascent RNA and transcriptional termination
  JOURNAL   Nucleic Acids Res 36 (3), 905-914 (2008)
   PUBMED   18086705
  REMARK    GeneRIF: Pcf11 is required for the efficient degradation of the 3'
            product of poly(A) site cleavage.
REFERENCE   9  (bases 1 to 6270)
  AUTHORS   Zhang,Z., Klatt,A., Henderson,A.J. and Gilmour,D.S.
  TITLE     Transcription termination factor Pcf11 limits the processivity of
            Pol II on an HIV provirus to repress gene expression
  JOURNAL   Genes Dev 21 (13), 1609-1614 (2007)
   PUBMED   17606639
  REMARK    GeneRIF: Pcf11 can act as a negative elongation factor to repress
            RNA Pol II gene expression in eukaryotic cells.
REFERENCE   10 (bases 1 to 6270)
  AUTHORS   de Vries,H., Ruegsegger,U., Hubner,W., Friedlein,A., Langen,H. and
            Keller,W.
  TITLE     Human pre-mRNA cleavage factor II(m) contains homologs of yeast
            proteins and bridges two other cleavage factors
  JOURNAL   EMBO J 19 (21), 5895-5904 (2000)
   PUBMED   11060040
  REMARK    GeneRIF: Human PCf11 is a pre-mRNA processing factor.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP000873.5.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Apr 28, 2021 this sequence version replaced NM_001346413.2.
            
            Summary: The protein encoded by this gene binds to CLP1 to form
            pre-mRNA cleavage factor IIm. The encoded protein is necessary for
            efficient Pol II transcription termination and may be involved in
            degradation of the 3' product of polyA site cleavage. [provided by
            RefSeq, Oct 2016].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (1).
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR7346977.2552290.1,
                                           SRR1803611.232134.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000690938.1/ ENSP00000508500.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-501               AP000873.5         27223-27723
            502-627             AP000873.5         31419-31544
            628-816             AP000873.5         33771-33959
            817-1011            AP000873.5         34299-34493
            1012-2126           AP000873.5         35692-36806
            2127-2310           AP000873.5         37217-37400
            2311-2794           AP000873.5         37507-37990
            2795-4362           AP000873.5         38520-40087
            4363-4459           AP000873.5         41910-42006
            4460-4579           AP000873.5         47177-47296
            4580-4685           AP000873.5         47806-47911
            4686-4869           AP000873.5         51100-51283
            4870-5025           AP000873.5         51946-52101
            5026-5118           AP000873.5         52491-52583
            5119-5154           AP000873.5         53130-53165
            5155-6270           AP000873.5         54771-55886
FEATURES             Location/Qualifiers
     source          1..6270
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q14.1"
     gene            1..6270
                     /gene="PCF11"
                     /note="PCF11 cleavage and polyadenylation factor subunit"
                     /db_xref="GeneID:51585"
                     /db_xref="HGNC:HGNC:30097"
                     /db_xref="MIM:608876"
     exon            1..501
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     CDS             310..5370
                     /gene="PCF11"
                     /note="isoform 1 is encoded by transcript variant 1;
                     PCF11p homolog; pre-mRNA cleavage complex 2 protein Pcf11;
                     pre-mRNA cleavage complex II protein Pcf11; PCF11,
                     cleavage and polyadenylation factor subunit, homolog"
                     /codon_start=1
                     /product="pre-mRNA cleavage complex 2 protein Pcf11
                     isoform 1"
                     /protein_id="NP_001333342.1"
                     /db_xref="CCDS:CCDS91554.1"
                     /db_xref="GeneID:51585"
                     /db_xref="HGNC:HGNC:30097"
                     /db_xref="MIM:608876"
                     /translation="MSEQTPAEAGAAGAREDACRDYQSSLEDLTFNSKPHINMLTILA
                     EENLPFAKEIVSLIEAQTAKAPSSEKLPVMYLMDSIVKNVGREYLTAFTKNLVATFIC
                     VFEKVDENTRKSLFKLRSTWDEIFPLKKLYALDVRVNSLDPAWPIKPLPPNVNTSSIH
                     VNPKFLNKSPEEPSTPGTVVSSPSISTPPIVPDIQKNLTQEQLIRQQLLAKQKQLLEL
                     QQKKLELELEQAKAQLAVSLSVQQETSNLGPGSAPSKLHVSQIPPMAVKAPHQVPVQS
                     EKSRPGPSLQIQDLKGTNRDPRLNRISQHSHGKDQSHRKEFLMNTLNQSDTKTSKTIP
                     SEKLNSSKQEKSKSGEKITKKELDQLDSKSKSKSKSPSPLKNKLSHTKDLKNQESESM
                     RLSDMNKRDPRLKKHLQDKTDGKDDDVKEKRKTAEKKDKDEHMKSSEHRLAGSRNKII
                     NGIVQKQDTITEESEKQGTKPGRSSTRKRSRSRSPKSRSPIIHSPKRRDRRSPKRRQR
                     SMSPTSTPKAGKIRQSGAKQSHMEEFTPPSREDRNAKRSTKQDIRDPRRMKKTEEERP
                     QETTNQHSTKSGTEPKENVENWQSSKSAKRWKSGWEENKSLQQVDEHSKPPHLRHRES
                     WSSTKGILSPRAPKQQQHRLSVDANLQIPKELTLASKRELLQKTSERLASGEITQDDF
                     LVVVHQIRQLFQYQEGKHRCNVRDSPTEENKGGLKKKPLLSDAELTYYEHKAKLKRTQ
                     VQHSFPRLDLLDPDIFDYPLTDALLSGIECEPSKSKHASRNSGAQFDRKEQFSERARR
                     LSPISGSRTYAENLSPHEGRRRHDEQVSAKGVREEQRSPFNDRFPLKRPRYEDSDKPF
                     VDSPASRFAGLDTNQRLTALAEDRPLFDGPSRPSVARDGPTKMIFEGPNKLSPRIDGP
                     PTPASLRFDGSPGQMGGGGPLRFEGPQGQLGGGCPLRFEGPPGPVGTPLRFEGPIGQA
                     GGGGFRFEGSPGLRFEGSPGGLRFEGPGGQPVGGLRFEGHRGQPVGGLRFEGPHGQPV
                     GGLRFDNPRGQPVGGLRFEGGHGPSGAAIRFDGPHGQPGGGIRFEGPLLQQGVGMRFE
                     GPHGQSVAGLRFEGQHNQLGGNLRFEGPHGQPGVGIRFEGPLVQQGGGMRFEGPSVPG
                     GGLRIEGPLGQGGPRFEGCHALRFDGQPGQPSLLPRFDGLHGQPGPRFERTPGQPGPQ
                     RFDGPPGQQVQPRFDGVPQRFDGPQHQQASRFDIPLGLQGTRFDNHPSQRLESVSFNQ
                     TGPYNDPPGNAFNAPSQGLQFQRHEQIFDSPQGPNFNGPHGPGNQSFSNPLNRASGHY
                     FDEKNLQSSQFGNFGNIPAPMTVGNIQASQQVLSGVAQPVAFGQGQQFLPVHPQNPGF
                     VQNPSGALPKAYPDNHLSQVDVNELFSKLLKTGILKLSQTDSATTQVSEVTAQPPPEE
                     EEDQNEDQDVPDLTNFTVEELKQRYDSVINRLYTGIQCYSCGMRFTTSQTDVYADHLD
                     WHYRQNRTEKDVSRKVTHRRWYYSLTDWIEFEEIADLEERAKSQFFEKVHEEVVLKTQ
                     EAAKEKEFQSVPAGPAGAVESCEICQEQFEQYWDEEEEEWHLKNAIRVDGKIYHPSCY
                     EDYQNTSSFDCTPSPSKTPVENPLNIMLNIVKNELQEPCDSPKVKEERIDTPPACTEE
                     SIATPSEIKTENDTVESV"
     exon            502..627
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            628..816
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            817..1011
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            1012..2126
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            2127..2310
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            2311..2794
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            2795..4362
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            4363..4459
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            4460..4579
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            4580..4685
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            4686..4869
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            4870..5025
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            5026..5118
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            5119..5154
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     exon            5155..6270
                     /gene="PCF11"
                     /inference="alignment:Splign:2.1.0"
     regulatory      6253..6258
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PCF11"
                     /note="hexamer: AATAGA"
     polyA_site      6270
                     /gene="PCF11"
                     /note="major polyA site"
ORIGIN      
        1 gcacgacgca gcggttggga acacagacat tttcggagct ggagccgcca ctgccgccgc
       61 cattttgtgt ctgtggagaa agaagcttct gtggcggctg gaagtggacg gagatcaccc
      121 gcgagacggc ggcgtttcat acccgaggtt ccccctgtgt cgtcccccat cccccctccg
      181 cggtcagcat gtggtgaagc cggagccgcg agagagccgg ggagaggaag aggagtcgga
      241 agggaggcgg ggtatccaga gcggcttcag cttcagctgc agcggacctc ggaggggggc
      301 cgcggcgcaa tgtcagagca gacgccggcc gaggccggtg ctgcgggggc ccgggaggac
      361 gcctgtcggg attatcagtc atcgctcgaa gacctgacct tcaatagcaa gccgcacatc
      421 aatatgctga ccattctagc cgaggagaac ctgcccttcg ccaaggagat cgtctctctc
      481 atcgaggccc aaaccgccaa ggctccttcc tcagagaagc ttcctgttat gtaccttatg
      541 gattctattg tgaaaaacgt tggaagagag tatctcactg cctttactaa aaatctagtt
      601 gcaacattta tttgtgtgtt tgaaaaggtg gatgaaaata ctaggaaaag tttatttaag
      661 ttacgttcta catgggatga aatattccct ttgaagaaac tttatgccct ggatgtcaga
      721 gtcaattcat tagatcctgc ttggcctatt aaacctctac cccccaatgt gaatacgtct
      781 agcatccatg tgaatcctaa atttttaaat aaatcgcccg aggagccttc aacacctggt
      841 acagtggtca gttcccctag catctccact cctccaattg ttcctgatat acaaaagaat
      901 cttacacaag aacaactaat aaggcagcag ttactggcaa agcaaaaaca gttgttagaa
      961 cttcagcaga aaaagctgga gcttgagcta gagcaagcta aggcacagtt ggcagtttct
     1021 cttagtgttc agcaggaaac atccaattta ggtcctggat ctgcaccatc caaattacat
     1081 gtttcacaga ttccccctat ggcagttaaa gctcctcatc aggttcctgt gcaatctgag
     1141 aaaagccgtc caggaccatc cttacaaatt caggatttaa aaggaactaa ccgggatcct
     1201 cgtctgaaca ggataagcca acattctcat ggaaaagatc agagtcacag gaaagaattt
     1261 ctaatgaaca cattaaacca gtctgatact aagacaagta aaactatacc ctctgaaaaa
     1321 ctaaattcat ccaagcaaga aaaaagtaaa tcaggtgaaa aaataaccaa gaaagaactt
     1381 gaccaattag attctaaatc gaaatcgaaa tcgaaatcac cctcaccttt gaaaaacaaa
     1441 ttatctcaca caaaagactt gaaaaatcaa gaatcggaaa gtatgaggtt gtctgatatg
     1501 aacaagagag atccaagatt aaaaaaacat cttcaggata agaccgatgg caaagatgat
     1561 gatgtgaaag agaagagaaa aactgcagaa aaaaaggata aagatgagca catgaagtca
     1621 tccgaacaca gactggctgg aagtagaaat aaaatcataa atggcattgt acaaaaacag
     1681 gatacaataa cagaagagtc agaaaaacag gggacaaaac cagggagatc gagtactaga
     1741 aagcgatcaa gatctcgatc acccaagtct aggtcaccaa ttatacattc cccaaagaga
     1801 agagataggc ggtcacccaa acgaaggcaa agaagtatgt ctccaacatc gacacctaaa
     1861 gctggaaaga ttcgccaatc tggagctaag cagtcacata tggaagagtt tacaccacct
     1921 tctagggaag acagaaatgc taagagaagt actaaacagg atattcggga tccaaggcga
     1981 atgaaaaaga ctgaagagga gcgaccacaa gaaactacaa atcagcattc tacaaagtca
     2041 ggcactgaac caaaggagaa tgtagaaaac tggcaaagtt ccaagtctgc caaaagatgg
     2101 aaatctggtt gggaagaaaa taaaagctta caacaggttg atgaacatag taaacctcct
     2161 catctgaggc atagggagag ctggtcaagc actaaaggaa ttttatcacc tcgagcccca
     2221 aagcagcaac agcatcgatt aagtgtagat gccaatcttc agattcctaa agagttaact
     2281 cttgcaagca aaagagaatt acttcaaaag acgagtgaac gtttagcatc tggtgaaatt
     2341 acacaggatg acttccttgt tgttgtgcat caaattcgac agctatttca gtatcaagaa
     2401 ggtaaacata gatgcaatgt acgggatagt cctacagaag aaaataaagg tggattaaaa
     2461 aagaaacctc tcttatctga tgctgaatta acctactatg aacataaagc aaaactgaaa
     2521 aggacacagg ttcagcattc atttccaaga cttgatctct tagatcctga tatttttgac
     2581 taccctttga ctgatgcctt gttgtctgga atagaatgtg agccatccaa aagtaaacat
     2641 gcaagtagga atagtggagc acagtttgac agaaaagaac aatttagtga aagagcaaga
     2701 cgtctttctc ctatatctgg gagtcgtact tatgctgaga atctttcacc ccatgagggc
     2761 cggagaagac atgacgagca agtctctgct aaaggtgtgc gagaagagca gagatctcca
     2821 ttcaatgatc gttttccact taagcgacct cgatatgaag attcagataa accatttgta
     2881 gatagtccag catcaagatt cgccggcctg gatacaaatc agcgacttac agctttagct
     2941 gaagacagac cgttatttga tggacctagt aggccatcag tagcaagaga tggcccaacg
     3001 aagatgattt ttgaaggacc caataaatta agccctcgaa ttgatggacc tcccacacca
     3061 gcttctcttc ggtttgatgg gtcaccagga caaatggggg gaggaggccc tttgagattt
     3121 gaggggccac aaggtcagct aggaggtggg tgtcctttga gatttgaagg tcctccagga
     3181 ccagtgggga cacctctgcg gtttgagggc ccaattggtc aagcaggagg aggtggtttt
     3241 cggtttgaag gttcccctgg tctgaggttt gagggatctc caggtggttt gagatttgag
     3301 ggaccaggag gccagcctgt gggtggtctg aggtttgagg gacatcgtgg tcaacctgtg
     3361 ggtggtctaa ggtttgaggg acctcatggt cagcctgtgg gtggacttag atttgataat
     3421 ccccgaggtc agcctgtagg tggacttaga tttgaggggg gtcatggtcc atcaggggct
     3481 gcgattaggt ttgatggacc tcatggtcag ccaggaggtg gaatcagatt tgagggccct
     3541 ttgctacagc aaggggttgg aatgaggttt gagggccccc atggtcagtc agtagctggt
     3601 ctgagatttg agggacaaca taatcaactt ggtgggaacc ttaggtttga gggtccacat
     3661 ggtcagccag gggttggtat caggtttgaa ggccctttag tccaacaagg aggtggaatg
     3721 aggtttgagg gtccttctgt accaggaggt ggcctgagaa ttgaagggcc tctgggtcaa
     3781 ggtggtccaa gatttgaagg ttgtcatgct ttaaggtttg atgggcagcc aggtcagccg
     3841 tcactcttgc caagatttga tggattacat ggtcagccag gtcctagatt tgaaaggact
     3901 cctggtcagc caggccctca gaggtttgat ggaccacctg gacagcaggt tcaacccaga
     3961 tttgacggtg tacctcaaag atttgatggt ccacaacatc agcaagcatc aaggtttgat
     4021 attcctcttg gtcttcaagg cacaagattt gacaatcatc cttcacaaag gcttgaatca
     4081 gtatctttca atcagactgg tccatataat gatccacctg gcaatgcttt taatgcccca
     4141 tcccaaggac tacagttcca aagacatgaa caaatatttg attcacctca aggaccaaat
     4201 tttaatggac cacatggccc tggaaaccag agtttctcta atccacttaa cagagcttct
     4261 ggacactatt ttgatgaaaa aaatcttcag agttctcaat ttggaaactt tggcaatata
     4321 cctgctccaa tgacagtagg aaatattcag gcatctcaac aggttctgag tggtgttgct
     4381 cagccagtag cttttggtca aggacaacag tttttaccag ttcatccaca aaatcctgga
     4441 tttgttcaga atccttcagg agccctccct aaggcatatc ctgataatca tctcagtcag
     4501 gtggatgtaa atgaattgtt ttcaaaattg ctaaaaacag gaattctcaa attgtcccaa
     4561 actgattcag ctacaacaca agtaagtgaa gtaactgctc agcctccccc tgaagaggag
     4621 gaagatcaaa atgaagatca agatgttcca gatcttacta attttacagt tgaagaattg
     4681 aaacaacgtt atgacagtgt tataaatcga ctgtacactg gtattcagtg ttactcttgt
     4741 ggaatgaggt ttacaacatc acagacagat gtttatgcag atcatttgga ctggcattat
     4801 cggcaaaata gaactgaaaa ggatgttagc cgaaaagtca ctcatagacg ttggtactac
     4861 agtttaacag actggataga atttgaggag atagctgatc tggaagaacg ggcaaagagc
     4921 cagttttttg aaaaggtgca tgaagaagtt gtgctcaaaa ctcaagaggc tgctaaagaa
     4981 aaagagttcc aaagtgtacc tgctggacca gctggagcag ttgagagttg tgaaatctgt
     5041 caagaacaat ttgaacaata ctgggatgaa gaagaggagg aatggcattt gaaaaatgct
     5101 attagagtag atggaaagat ttatcatcca tcatgttatg aagattatca aaatacatct
     5161 tcatttgatt gtacaccatc tcccagcaag acaccagttg aaaacccctt gaatattatg
     5221 ttgaacattg tcaaaaacga attgcaggaa ccctgtgaca gtcccaaagt taaggaagaa
     5281 cgaattgata caccaccagc ttgtacagag gaaagcatag caacaccctc tgaaattaaa
     5341 acagaaaatg acacagtcga gtcagtttaa ataaaatgag aaaggtatgt ttttcttttt
     5401 taaaaaagct gctgttggat ctagaaggtg aagaattttt ttatgtatat atagacatat
     5461 ctatataaat tgtctggctg aggcagggcc ttcagctatc atttggttaa taaatacatt
     5521 ttagtatttg catttcctac tgcctgcaga gtttcaggtg cttgttgtgt gaaagttctg
     5581 tagatgtgtg caaatttaac gaaatgaaat tgtatgtgta aaaatgtacg atttttcact
     5641 gtgcaactgt aaattataaa taaaaaatat ttttgctatt catggagtgt aatatttatg
     5701 cacaccatca aatagtttct gtacttttta ttgggtaaaa atggaattga acagcaacct
     5761 caacataaga ttttttttct agtagcctcc cactgattaa agaagcaagt ttgaggtttc
     5821 atccttcaaa agggggttcc gagagagcac cgtagggctt ttctcaaata gaaaagccag
     5881 attttgaaaa aattttaaag ataaaatagg acatattttg cagatatata tatatatata
     5941 cacaaacaca tctccaggta tagagaacca tccagatgtt cacttttgaa aatatctaat
     6001 gatgcaaagt tttattcttg aacttggaca ctgatgccat caaacaatta acaaatatat
     6061 ttaagtacta aaggtgattt tttttttaaa gactttttca aattgtcaaa tgatttaatg
     6121 cagatgaaca tatttctatt ttaagtaacg ggaatctgta agaatgtttg cttgagatat
     6181 ggttaacttt tttcttttgt tggttttgac ttagatggac accatgagat gttaatattc
     6241 atacatgtaa taaatagaat gatgaagaaa
//
