LOCUS       NM_004898              10470 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens clock circadian regulator (CLOCK), transcript variant
            2, mRNA.
ACCESSION   NM_004898
VERSION     NM_004898.4
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 10470)
  AUTHORS   Rashed,N., Liu,W., Zhou,X., Bode,A.M. and Luo,X.
  TITLE     The role of circadian gene CLOCK in cancer
  JOURNAL   Biochim Biophys Acta Mol Cell Res 1871 (7), 119782 (2024)
   PUBMED   38871225
  REMARK    GeneRIF: The role of circadian gene CLOCK in cancer.
            Review article
REFERENCE   2  (bases 1 to 10470)
  AUTHORS   Otobe,Y., Jeong,E.M., Ito,S., Shinohara,Y., Kurabayashi,N.,
            Aiba,A., Fukada,Y., Kim,J.K. and Yoshitane,H.
  TITLE     Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for
            PER-dependent inhibition in circadian clock of mammalian cells
  JOURNAL   Proc Natl Acad Sci U S A 121 (23), e2316858121 (2024)
   PUBMED   38805270
  REMARK    GeneRIF: Phosphorylation of DNA-binding domains of CLOCK-BMAL1
            complex for PER-dependent inhibition in circadian clock of
            mammalian cells.
REFERENCE   3  (bases 1 to 10470)
  AUTHORS   Oliveira,R., Neves-Costa,A., Pedroso,D., Paixao,T., Barros,A.B.,
            Moita,L.F. and Gil-Gouveia,R.
  TITLE     CLOCK gene circannual expression in cluster headache
  JOURNAL   Cephalalgia 44 (4), 3331024241247845 (2024)
   PUBMED   38676534
  REMARK    GeneRIF: CLOCK gene circannual expression in cluster headache.
            Erratum:[Cephalalgia. 2024 Dec;44(12):3331024241303592. doi:
            10.1177/03331024241303592.. PMID: 39691983]
REFERENCE   4  (bases 1 to 10470)
  AUTHORS   Wang,J., Zhou,Y., Zhang,M., Wu,Y., Wu,Q., Su,W., Xu,M., Wu,J.,
            Zhang,M., Shuai,J., Tang,W., Lv,J., Wu,M. and Xia,Z.
  TITLE     YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway
            inflammation through LLPS
  JOURNAL   Cell Rep 43 (3), 113947 (2024)
   PUBMED   38492220
  REMARK    GeneRIF: YTHDF1-CLOCK axis contributes to pathogenesis of allergic
            airway inflammation through LLPS.
REFERENCE   5  (bases 1 to 10470)
  AUTHORS   Doi,M., Hirayama,J. and Sassone-Corsi,P.
  TITLE     Circadian regulator CLOCK is a histone acetyltransferase
  JOURNAL   Cell 125 (3), 497-508 (2006)
   PUBMED   16678094
REFERENCE   6  (bases 1 to 10470)
  AUTHORS   Wager-Smith,K. and Kay,S.A.
  TITLE     Circadian rhythm genetics: from flies to mice to humans
  JOURNAL   Nat Genet 26 (1), 23-27 (2000)
   PUBMED   10973243
  REMARK    Review article
REFERENCE   7  (bases 1 to 10470)
  AUTHORS   Hogenesch,J.B., Gu,Y.Z., Moran,S.M., Shimomura,K., Radcliffe,L.A.,
            Takahashi,J.S. and Bradfield,C.A.
  TITLE     The basic helix-loop-helix-PAS protein MOP9 is a brain-specific
            heterodimeric partner of circadian and hypoxia factors
  JOURNAL   J Neurosci 20 (13), RC83 (2000)
   PUBMED   10864977
REFERENCE   8  (bases 1 to 10470)
  AUTHORS   Steeves,T.D., King,D.P., Zhao,Y., Sangoram,A.M., Du,F.,
            Bowcock,A.M., Moore,R.Y. and Takahashi,J.S.
  TITLE     Molecular cloning and characterization of the human CLOCK gene:
            expression in the suprachiasmatic nuclei
  JOURNAL   Genomics 57 (2), 189-200 (1999)
   PUBMED   10198158
  REMARK    GeneRIF: essential regulator of circadian rhythms
REFERENCE   9  (bases 1 to 10470)
  AUTHORS   Jin,X., Shearman,L.P., Weaver,D.R., Zylka,M.J., de Vries,G.J. and
            Reppert,S.M.
  TITLE     A molecular mechanism regulating rhythmic output from the
            suprachiasmatic circadian clock
  JOURNAL   Cell 96 (1), 57-68 (1999)
   PUBMED   9989497
REFERENCE   10 (bases 1 to 10470)
  AUTHORS   Hogenesch,J.B., Gu,Y.Z., Jain,S. and Bradfield,C.A.
  TITLE     The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally
            active complexes with circadian and hypoxia factors
  JOURNAL   Proc Natl Acad Sci U S A 95 (10), 5474-5479 (1998)
   PUBMED   9576906
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA658950.1, AK223549.1 and
            AC069200.6.
            
            On Nov 22, 2018 this sequence version replaced NM_004898.3.
            
            Summary: The protein encoded by this gene plays a central role in
            the regulation of circadian rhythms. The protein encodes a
            transcription factor of the basic helix-loop-helix (bHLH) family
            and contains DNA binding histone acetyltransferase activity. The
            encoded protein forms a heterodimer with ARNTL (BMAL1) that binds
            E-box enhancer elements upstream of Period (PER1, PER2, PER3) and
            Cryptochrome (CRY1, CRY2) genes and activates transcription of
            these genes. PER and CRY proteins heterodimerize and repress their
            own transcription by interacting in a feedback loop with
            CLOCK/ARNTL complexes. Polymorphisms in this gene may be associated
            with behavioral changes in certain populations and with obesity and
            metabolic syndrome. Alternative splicing results in multiple
            transcript variants. [provided by RefSeq, Jan 2014].
            
            Transcript Variant: This variant (2) differs in the 5' UTR compared
            to variant 1. Both variants 1 and 2 encode the same protein.
            
            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 :: SRR1803614.283476.1,
                                           SRR1660807.10322.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000513440.6/ ENSP00000426983.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-60                DA658950.1         1-60
            61-2180             AK223549.1         1-2120
            2181-2259           AC069200.6         76438-76516         c
            2260-3351           AK223549.1         2200-3291
            3352-10470          AC069200.6         60594-67712         c
FEATURES             Location/Qualifiers
     source          1..10470
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q12"
     gene            1..10470
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /note="clock circadian regulator"
                     /db_xref="GeneID:9575"
                     /db_xref="HGNC:HGNC:2082"
                     /db_xref="MIM:601851"
     exon            1..128
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            129..282
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            283..374
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            375..464
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     CDS             418..2958
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /EC_number="2.3.1.48"
                     /note="circadian locomoter output cycles kaput protein;
                     class E basic helix-loop-helix protein 8; clock homolog"
                     /codon_start=1
                     /product="circadian locomoter output cycles protein kaput"
                     /protein_id="NP_004889.1"
                     /db_xref="CCDS:CCDS3500.1"
                     /db_xref="GeneID:9575"
                     /db_xref="HGNC:HGNC:2082"
                     /db_xref="MIM:601851"
                     /translation="MLFTVSCSKMSSIVDRDDSSIFDGLVEEDDKDKAKRVSRNKSEK
                     KRRDQFNVLIKELGSMLPGNARKMDKSTVLQKSIDFLRKHKEITAQSDASEIRQDWKP
                     TFLSNEEFTQLMLEALDGFFLAIMTDGSIIYVSESVTSLLEHLPSDLVDQSIFNFIPE
                     GEHSEVYKILSTHLLESDSLTPEYLKSKNQLEFCCHMLRGTIDPKEPSTYEYVKFIGN
                     FKSLNSVSSSAHNGFEGTIQRTHRPSYEDRVCFVATVRLATPQFIKEMCTVEEPNEEF
                     TSRHSLEWKFLFLDHRAPPIIGYLPFEVLGTSGYDYYHVDDLENLAKCHEHLMQYGKG
                     KSCYYRFLTKGQQWIWLQTHYYITYHQWNSRPEFIVCTHTVVSYAEVRAERRRELGIE
                     ESLPETAADKSQDSGSDNRINTVSLKEALERFDHSPTPSASSRSSRKSSHTAVSDPSS
                     TPTKIPTDTSTPPRQHLPAHEKMVQRRSSFSSQSINSQSVGSSLTQPVMSQATNLPIP
                     QGMSQFQFSAQLGAMQHLKDQLEQRTRMIEANIHRQQEELRKIQEQLQMVHGQGLQMF
                     LQQSNPGLNFGSVQLSSGNSSNIQQLAPINMQGQVVPTNQIQSGMNTGHIGTTQHMIQ
                     QQTLQSTSTQSQQNVLSGHSQQTSLPSQTQSTLTAPLYNTMVISQPAAGSMVQIPSSM
                     PQNSTQSAAVTTFTQDRQIRFSQGQQLVTKLVTAPVACGAVMVPSTMLMGQVVTAYPT
                     FATQQQQSQTLSVTQQQQQQSSQEQQLTSVQQPSQAQLTQPPQQFLQTSRLLHGNPST
                     QLILSAAFPLQQSTFPQSHHQQHQSQQQQQLSRHRTDSLPDPSKVQPQ"
     exon            465..524
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            525..673
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            674..765
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            766..855
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            856..976
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            977..1090
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            1091..1209
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            1210..1292
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            1293..1399
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            1400..1547
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            1548..1623
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            1624..1765
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            1766..1866
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            1867..1956
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            1957..2109
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            2110..2319
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            2320..2522
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            2523..2778
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     exon            2779..10470
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3529..3534
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /note="hexamer: GATAAA"
     polyA_site      3550
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /note="major polyA site"
     regulatory      10326..10331
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /note="hexamer: AATAAA"
     polyA_site      10347
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /note="major polyA site"
     regulatory      10445..10450
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /note="hexamer: ATTAAA"
     polyA_site      10470
                     /gene="CLOCK"
                     /gene_synonym="bHLHe8; KAT13D"
                     /note="major polyA site"
ORIGIN      
        1 gctgacgacg catgcgccgg gagggggcgc aatcacggac tcggcttgcg gctgccggtt
       61 taaaaaagga aaccccggag agcgagagcg cgaaggaaat ctggccgccg ccgccgcgag
      121 cgctcccgaa tttttacttg ttcctgcaaa gctgctggag ctcagaagct gattctatca
      181 cattgtaaga tgcctttgga taattctaca gtcctcttaa atgaatcttt agaacttggc
      241 aagtctcact agataccttc aatcatcatt ttgagctcaa agaattctga gacttatggt
      301 tggtcatata gaagagtacc ttgaacctat agtttcctga agaatcagtt taaaagatcc
      361 aaggagtaca aaaggagaag tacaaatgtc tactacaaga cgaaaacgta gtatgttatg
      421 ttgtttaccg taagctgtag taaaatgagc tcgattgttg acagagatga cagtagtatt
      481 tttgatgggt tggtggaaga agatgacaag gacaaagcga aaagagtatc tagaaacaaa
      541 tctgaaaaga aacgtagaga tcaatttaat gttctcatta aagaactggg atccatgctt
      601 cctggtaatg ctagaaagat ggacaaatct actgttctgc agaaaagcat tgatttttta
      661 cgaaaacata aagaaatcac tgcacagtca gatgctagtg aaattcgaca ggactggaaa
      721 cctacattcc ttagtaatga agagtttaca caattaatgt tagaggctct tgatggtttt
      781 tttttagcaa tcatgacaga tggaagcata atatatgtgt ctgagagtgt aacttcatta
      841 cttgaacatt taccatctga tcttgtggat caaagtatat ttaattttat cccagaaggg
      901 gaacattcag aggtttataa aatactctct actcatctgc tggaaagtga ttcattaacc
      961 ccagaatatt taaaatcaaa aaatcagtta gaattctgtt gtcacatgct gcgaggaaca
     1021 atagacccaa aggagccatc tacctatgaa tatgtaaaat ttataggaaa tttcaaatct
     1081 ttaaacagtg tatcctcttc agcacacaat ggttttgaag gaactataca acgcacacat
     1141 aggccatctt atgaagatag agtttgtttt gtagctactg tcaggttagc tacacctcag
     1201 ttcatcaagg aaatgtgcac tgttgaagaa cccaatgaag agtttacatc tagacatagt
     1261 ttagaatgga agtttctgtt tctagatcac agggcaccac ccataatagg gtatttgcca
     1321 tttgaagttc tgggaacatc aggctatgat tactatcatg tggatgacct agaaaatttg
     1381 gcaaaatgtc atgagcactt aatgcaatat gggaaaggca aatcatgtta ttataggttc
     1441 ctgactaagg ggcaacagtg gatttggctt cagactcatt attatatcac ttaccatcag
     1501 tggaattcaa ggccagagtt tattgtttgt actcacactg tagtaagtta tgcagaagtt
     1561 agggctgaaa gacgacgaga acttggcatt gaagagtctc ttcctgagac agctgctgac
     1621 aaaagccaag attctgggtc agataatcgt ataaacacag tcagtctcaa ggaagcattg
     1681 gaaaggtttg atcacagccc aaccccttct gcctcttctc ggagttcaag aaaatcatct
     1741 cacacggccg tctcagaccc ttcctcaaca ccaaccaaga tcccgacgga tacgagcact
     1801 ccacccaggc agcatttacc agctcatgag aagatggtgc aaagaaggtc atcatttagt
     1861 agtcagtcca taaattccca gtctgttggt tcatcattaa cacagccagt gatgtctcaa
     1921 gctacaaatt taccaattcc acaaggcatg tcccagtttc agttttcagc tcaattagga
     1981 gccatgcaac atctgaaaga ccaattggaa caacggacac gcatgataga agcaaatatt
     2041 catcggcaac aagaagaact aagaaaaatt caagaacaac ttcagatggt ccatggtcag
     2101 gggctgcaga tgtttttgca acaatcaaat cctgggttga attttggttc cgttcaactt
     2161 tcttctggaa attcatctaa tatccagcaa cttgcaccta taaatatgca aggccaagtt
     2221 gttcctacta accagattca aagtggaatg aatactggac acattggcac aactcagcac
     2281 atgatacaac aacagacttt acagagtaca tcaactcaga gtcaacaaaa tgtactgagt
     2341 gggcacagtc agcaaacatc tctacccagt cagacacaga gcactcttac agccccactg
     2401 tataacacta tggtgatttc tcagcctgca gccggaagca tggtccagat tccatctagt
     2461 atgccacaaa acagcaccca gagtgctgca gtaactacat tcactcagga caggcagata
     2521 agattttctc aaggtcaaca acttgtgacc aaattagtga ctgctcctgt agcttgtggg
     2581 gcagtcatgg tacctagtac tatgcttatg ggccaggtgg tgactgcata tcctactttt
     2641 gctacacaac agcaacagtc acagacattg tcagtaacgc agcagcagca gcagcagagc
     2701 tcccaggagc agcagctcac ttcagttcag caaccatctc aggctcagct gacccagcca
     2761 ccgcaacaat ttttacagac ttctaggttg ctccatggga atccctcaac tcaactcatt
     2821 ctctctgctg catttcctct acaacagagc accttccctc agtcacatca ccagcaacat
     2881 cagtctcagc aacagcagca actcagccgg cacaggactg acagcttgcc cgacccttcc
     2941 aaggttcaac cacagtagca cacgtgcttc ctctcttgac atcaagggag gaaggggatg
     3001 gcccattaag agttactcag atgacctgag gaaaggaggg aaagttccag cagtttcatg
     3061 agatgcagta ttgagtgttc tagttcctgg aattagttgg cagagaaaat gctgcctagt
     3121 gctacagatg tacattaaat accagccagc aggaggtgat cataggggca tagccagttc
     3181 tgacagtgtt ttaggtgcct ggatattttt tgatggaaaa agaatatatt gccaaatatt
     3241 aagaagctca gctatgaaat gacctccagg gaatcagaaa ggcactaatg atgttagtaa
     3301 cttttagtgg ttctgtgcct cttatcaagt gttacagagg acataccact gccatgtcag
     3361 gggtttgctt acagtgatgc catgaagaca gtccagtaga cttggtagcg accccctccc
     3421 ccaacccctc tcccttttca gataatgatg gaacagtaat tactttcaga atgttgtgtg
     3481 ggttcaaatt ctctatgtac agatgatgta aaaatatgta tatgtctaga taaaaggaga
     3541 gaaagcaaaa cattttgtat gctgcatgaa agcgttatct cttccttaca ggtgtgagca
     3601 cctttcctga aattctgaca ccatgtgcaa actgatccat cctgtttttc cttttgttta
     3661 caacacagta gtgttctgtt cacttttccg gggcacaagt ttttttgttc atactttggc
     3721 tgtgatgtca cagtttgttc agtgaggtat gatgtgctgc tgggaatgga tttttttttt
     3781 caggttaaat tattgataca acaggatttt caagttattc agaaatatcc ctcatttcat
     3841 tatttttcaa ttatgtttga aaataggatt tgcactgctt tattttaggt ggctgggagt
     3901 tttgattgca tattttgtta tagttcatag ttggaaatat ttgcgtaaat ggttttcaac
     3961 aagcctgaaa gtaatttcaa gaatgtttca gttatagagg taaaatttgc acacaaaaca
     4021 tcttaggcac tttttaacat tctcaatcat gggaatttta acttttggga tttgttgaaa
     4081 tcttttttat tatccttcac aatttcaatg cttcttttag tcagaaatga ttcagggtta
     4141 tttgagggga aaaaacccca tagtgccttg attttaattc aggtgataac tcaccatctt
     4201 gaagtcattg tccggtttcc gtagcagttt tgaaacctta gtaccttttt aacagcatgt
     4261 gggtgtcagt gtcattatta gtctcctaat aagttcctct gaagactgct atcagtctct
     4321 tggactggag gtacaaataa tttagaaata aaagatgata acctaacact atcatagtta
     4381 ttaatgtgat cctaaaattg tttcctaaat cagcattttt ctttagtcat ttaagaattt
     4441 accagaaata tttgctcaat atgatcttga tattcctaca aagaaaaaag aaggggtagg
     4501 gatttggcta tgccttcact acaacattag aatattgtaa ctcacatgcc ttctaaacgt
     4561 gaactaagat ttcctttggc aatatcatat tctaaaagta ataaattcca atacaagtta
     4621 catacattta aaaaacattt tacagatttt atggtactaa tgaaatttac agtgatagaa
     4681 caaaagagga ttagtagaaa atacattatt agaatataaa aaatgttatt actgaggaaa
     4741 gggaggagag gacaagtgta ataaatcaaa attgacctca aaagaaaatg tgtaacagag
     4801 ttgaggttgt taaaacagaa aaggttctga ataatgaaga ttaacctaat gcagaattgc
     4861 taggtaaaga ggtcagggga atgctaagcc agttcttaag acttctctgt cctctgcttt
     4921 gctgttatcc ttaaggcata tactttgtct ttctgcagaa aattctacct ggctacaatt
     4981 actttgaaca ttaatgttga aaaagaaaac aaccaaagaa aattggtact tacccttcta
     5041 caaaagaagt gtgactagat atcaatcagt aattaacata tcaaggagct cttctagcta
     5101 aatgaccatc cagtagagat ttcccacatt cccatgaata tcaagaatag ttgtcagaat
     5161 atgtatgtac ctgagcatat gtacacagac aagggggatg ttgtggaata tggcaatagc
     5221 attgttcttc tcccctttca aattgccttt cttgacctta tgccattcca tatatatctg
     5281 agttgtgcct catttattta ttggcaatac ctagtgatac ggatttagct aacaaaagat
     5341 atgaagaact attatattga ggcctgtcct ctacatacca cacttaaaag atggtgaact
     5401 gtgagtacta cttaggttga cagcaacaaa gcataagaca agccccaggt aaacgtctaa
     5461 actgtttact cacattgtcc tactccagcc ccttcaatta tttcccatct ccacaaatag
     5521 tcgggggaaa aaattaaaat tttcctttat gattcttact gttcttcgca gctcatcttt
     5581 tcctgcttag aattaaccat tgctaattta aaggagcagc tagctgcttt tctgtcagtc
     5641 tgaagcgtag tagtggaaga ggtagtaagc accagctgcc tctttgctgc tttgttttcc
     5701 tcctgattct cttaaatttg ggttgcaaag ctatcccgcc ccccaccctg ccccatgaaa
     5761 cttgagcatt caaatgaaga ttcagcagtg tctgttcttc atttctatag ccaaagctgt
     5821 tagttaaaat cccaaatcta tagcatttaa agataccaaa tagaaacacc ttccagcttt
     5881 aaaaaaaaaa aaaaaaaagt cttccctctg ctttattctc actttcttaa aaacacttat
     5941 tctgggtggt actttttagg taagaaacta ctgagtttca ggaaaaatgc tagctactct
     6001 gcagttaccg tgctttggac ttgcagttat catagttttg ggagagtcag tattgtttaa
     6061 caaatgcaag tgagaactag aagggttaat aaagttgctc cttagagtgg tgtcaaacca
     6121 gaaccgagac acttaaaaag tacttcattt tttgaatgga aaatattgga gaaaagtatg
     6181 ggagatgcag gtagcatgtg agtaaatact acggtctagc cttcgagcat cccaaattcc
     6241 gggggtaact tgacagtgct gtgctctcct ttgtcattta tatctggctt aggaatggaa
     6301 tagtaataac aagatgccag tgatttggaa tagtttgtta tagaacattc agtgcaaaat
     6361 agtgaaaatg tttggtcttc agaagtgctg tagttgttgg tcattgcctt aaagcagtct
     6421 gcttgacgct aggagcactg aagcagtcca gctccatcaa gagcactgtt gaagggagaa
     6481 gaacccttgt tcaggaagcc ttagaaaggg atccttaaaa tagtactcta cgcagacaag
     6541 tgaaaattct tttaaactgg atattactca acatgttttc agatgtttcc actacattga
     6601 ggcaaacttt ttaaaagtgg aatgcaaata gcattttact ttagtatttc tgcttttttc
     6661 tttctgtttc tttggtaatt gaaagtttgt tgatgaatat ttgtgtaaaa cgcattcaag
     6721 tctataacct ttccaattac ctgtggccct tagtcccaca ggagtccctg ttggaagggg
     6781 gtaaacactg gatattaatg ttgctgagtg agtctttcta gccaggacaa gctgattgga
     6841 atttttgaat ggtagagaag aaacagcaca aaggcacttg ccattttaag tgtttggaga
     6901 aagagaacct tttaagtttg gattgggtga gctttcttct aaaaggagct tctgaagtaa
     6961 ttgcaaagga atagaatcga ctatttttat agtatattta atatatttgt atataactat
     7021 aataggaacc ctctacatgc ctcccacttt tctaatttac ttcccctttt gccatagcac
     7081 tagtatagcc tcatccgcat gggtaatgtg cctattgtca gcctaccaaa agatagtgct
     7141 gctgctttat gagacaggtg agaagaccca actctcatgc ctggggatcc tttacggaag
     7201 gaatagcaca cacttttaaa acaacatacc acagtctaaa agcatcattt tgaaatgtaa
     7261 caagcacttt attgcaatta ctcattttga taaagtttat tcttaggcgt taaccatttc
     7321 taaaggatcc ccaaatcatc acttacttag gtgaaattat ataaaatgac acatttctga
     7381 gaaatgttta ggtccagtga accgtagttg gtttatggga gtgatttcaa gatagccaaa
     7441 tgaactttga tttttgtttt gaatgtggtg gagtcaagag attgtagatg cctagtttga
     7501 tttaaacact attgtaaacc tatcttgcct attgtgtgga caccaaaaga gaccaatgag
     7561 cctgtttatt tttcagaggt ctaggaaaat tgcatccgtg tgagtagatg tacagaacta
     7621 atctaaaagt gattgctagt aacattttag aatataataa tttcaagaat tattctgagt
     7681 gttttaaatg tgccctgaaa tgttggcatg tcatttcagc atttccattt gaattgctct
     7741 tgtaatattt ttgcacaaaa aggactgaga aaaagaatac tttggttaaa ggaaaaaaat
     7801 agtataattt ggtctttaat tttaatgtct cctgtggaaa cactggggat gaattttgtt
     7861 ggcacagtta ttcaggatat ttaaaacagt gttgaacagt tcacaagaaa ttaagcaaac
     7921 ttggatttta aaaattaaaa tactttcttt ccatgtgact gttttgcata gttttttccc
     7981 cctatgtcat aacactacat tccttgtttt tcttaaataa aatactctgc aggttttgtt
     8041 gtgagtgttt ataacagtat tttgtaagct gcctgggttt cctcagggaa acattattta
     8101 gtggaatagg atatagttta tggagagaca actaagtgaa attccatcac caccaccagc
     8161 aaacactgag gtgctgcatt aagtgacaat caaactagta agtatttatg aaagaattta
     8221 gaaaggggtt caaagaagca attgctttta aagcagttct ctggggttct tgaataaaaa
     8281 tggctaaatg tatttattta tattttaaaa tacctgtgtg ttctgttttc tcatcaaagt
     8341 gatttcggtg tcatgtattt aatgtgtggt ttgttttgtt ttgcaccata ttcttcttag
     8401 ggaactggct ctgatttggg gtgcagtcac caactctcat gataatcttt acggacagtc
     8461 tgaatctact ttacttcagg acggcagtgg aggggccaac tccagatgcc cctgcacttc
     8521 cctcctcaag tcatctaaga aagaatttta gaaataactc ctttcaaatc tgattcatac
     8581 agttccaacc tttttctagt ttcacttgct gccttctttg ttttatgggc actttttgtg
     8641 tgattacttc cccaacacag tcaaaggcca gtatgacaga accaatggca catgatgcct
     8701 ctattttgcc catttgggga aatgttagta aaagaaatag catcttttaa tggctgtcat
     8761 tatcatatcc atattaaaat ccatttaaag ttcttaaatt tggcggaata atgtatacag
     8821 gctgtaaact tctacaaaaa atgtttgctg tctttaatat ggtgtcaagt tacttggtcc
     8881 tttgaaaaca aaacaaaact tccatacaca gcactgccca gtaaagcagt gttggaatat
     8941 tggaaaccta gacatttgag gatccttctt gctcacaagc attggaacag aatcctccac
     9001 tttaggactc agagaagcta tggagtccca caggctaggt atagcacaca acttagagaa
     9061 cggtagttaa agcacgtcaa ccacaattga atttaatgat ctaaaaaata tttcttaact
     9121 ctgagggtta aactgaagat acgttttcaa ataaaagctt ttaaatttct taggaaacaa
     9181 actgtgacat cgcttttaaa aatgacattc aaatgtttat aatgtgtgtt tttgagttgg
     9241 cttggactag tgcaagttca ctgctggcaa tggttatgcc agtagttaag ttaaaataag
     9301 ttgttacctt cagattgatg tcttgtataa ccagacaatc atcttcaagc aaaaaaattg
     9361 gccaggaaat gtctttttaa aaaaaaaaaa aaaaaaaaag atgtgtcagc cagaacagtt
     9421 accattcaga ccatactgga atgattttga aatctttact atggtttaag ttggggaagg
     9481 cctcagtatg gcattttcat attcactcta tgtaaagatt gaagcccaaa gatgagttaa
     9541 attcagtgct gtattgaaac cagtcagtgc aaaaaaaaaa aaaaagtttt acctttgtaa
     9601 atttttcatt gttaacatca gttggtagtt gttaaaacat gcaccaaatt ctttataatg
     9661 ttctgtgtgg ttctcaatgt gatattcttg acattgctgt ccttactgct tggttcttgg
     9721 ttttaaatta aaaagtagat gtagctcatc atttttactt ccaaaacggt ggagctaaaa
     9781 acggctaatt gatcttgaga taagaatacc ctttactaag gcaaagattt aattgaaatc
     9841 caaaatgatt tatagaaacg aaaggcattt tccatttgtt gtcttctgcc gaaattctga
     9901 attgcataca cacatgaagg ataatgaatg gtttcaacgg tgctatatta ggttctctga
     9961 ttttcatgac ctatgtatgt ttggaaatac aatattgtat aaaatgtgga tcgttttgtt
    10021 accgatttaa tattgccatt ttaatttggt gtaacaattg gttacacttg tttttcaaag
    10081 ctatcctttg aggagaaagt caaaatgtgt tgttagccta cctccactca ggcctcttgc
    10141 tgtgtaatca ttattccagg ttatgatgtg catagctttt aaaactgcgt gtactattat
    10201 tctgctcttt cccatactct tgtcatgtat tcagaaccta aacttatagc aaaagagcca
    10261 agcagtagca gtttttgtaa atgtaaaaat aattagatcc agactttgtt tccttcaatt
    10321 ttaaaaataa aaaatacctc agtgctatgt ttttcagtta tcacctgcat ttctcaaaaa
    10381 ataacacctg cttcatgtgg cacataactt gtaagaatca cattttggat tttaaagaaa
    10441 gactattaaa tattttaaga tcactatcaa
//
