LOCUS       NM_016218              14623 bp    mRNA    linear   PRI 13-DEC-2024
DEFINITION  Homo sapiens DNA polymerase kappa (POLK), transcript variant 1,
            mRNA.
ACCESSION   NM_016218
VERSION     NM_016218.6
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 14623)
  AUTHORS   Ribeiro,D.L., Latancia,M.T., de Souza,I., Ariwoola,A.A., Mendes,D.,
            Rocha,C.R.R., Lengert,A.V.H. and Menck,C.F.M.
  TITLE     Temozolomide resistance mechanisms: unveiling the role of
            translesion DNA polymerase kappa in glioblastoma spheroids in vitro
  JOURNAL   Biosci Rep 44 (5) (2024)
   PUBMED   38717250
  REMARK    GeneRIF: Temozolomide resistance mechanisms: unveiling the role of
            translesion DNA polymerase kappa in glioblastoma spheroids in
            vitro.
REFERENCE   2  (bases 1 to 14623)
  AUTHORS   Maghsoud,Y., Roy,A., Leddin,E.M. and Cisneros,G.A.
  TITLE     Effects of the Y432S Cancer-Associated Variant on the Reaction
            Mechanism of Human DNA Polymerase kappa
  JOURNAL   J Chem Inf Model 64 (10), 4231-4249 (2024)
   PUBMED   38717969
  REMARK    GeneRIF: Effects of the Y432S Cancer-Associated Variant on the
            Reaction Mechanism of Human DNA Polymerase kappa.
REFERENCE   3  (bases 1 to 14623)
  AUTHORS   Pathira Kankanamge,L.S., Mora,A., Ondrechen,M.J. and Beuning,P.J.
  TITLE     Biochemical Activity of 17 Cancer-Associated Variants of DNA
            Polymerase Kappa Predicted by Electrostatic Properties
  JOURNAL   Chem Res Toxicol 36 (11), 1789-1803 (2023)
   PUBMED   37883788
  REMARK    GeneRIF: Biochemical Activity of 17 Cancer-Associated Variants of
            DNA Polymerase Kappa Predicted by Electrostatic Properties.
REFERENCE   4  (bases 1 to 14623)
  AUTHORS   Yudkina,A.V. and Zharkov,D.O.
  TITLE     Miscoding and DNA Polymerase Stalling by Methoxyamine-Adducted
            Abasic Sites
  JOURNAL   Chem Res Toxicol 35 (2), 303-314 (2022)
   PUBMED   35089032
  REMARK    GeneRIF: Miscoding and DNA Polymerase Stalling by
            Methoxyamine-Adducted Abasic Sites.
REFERENCE   5  (bases 1 to 14623)
  AUTHORS   Lancey,C., Tehseen,M., Bakshi,S., Percival,M., Takahashi,M.,
            Sobhy,M.A., Raducanu,V.S., Blair,K., Muskett,F.W., Ragan,T.J.,
            Crehuet,R., Hamdan,S.M. and De Biasio,A.
  TITLE     Cryo-EM structure of human Pol kappa bound to DNA and
            mono-ubiquitylated PCNA
  JOURNAL   Nat Commun 12 (1), 6095 (2021)
   PUBMED   34667155
  REMARK    GeneRIF: Cryo-EM structure of human Pol kappa bound to DNA and
            mono-ubiquitylated PCNA.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 14623)
  AUTHORS   Gerlach,V.L., Feaver,W.J., Fischhaber,P.L. and Friedberg,E.C.
  TITLE     Purification and characterization of pol kappa, a DNA polymerase
            encoded by the human DINB1 gene
  JOURNAL   J Biol Chem 276 (1), 92-98 (2001)
   PUBMED   11024016
REFERENCE   7  (bases 1 to 14623)
  AUTHORS   Ohashi,E., Ogi,T., Kusumoto,R., Iwai,S., Masutani,C., Hanaoka,F.
            and Ohmori,H.
  TITLE     Error-prone bypass of certain DNA lesions by the human DNA
            polymerase kappa
  JOURNAL   Genes Dev 14 (13), 1589-1594 (2000)
   PUBMED   10887153
REFERENCE   8  (bases 1 to 14623)
  AUTHORS   Johnson,R.E., Prakash,S. and Prakash,L.
  TITLE     The human DINB1 gene encodes the DNA polymerase Poltheta
  JOURNAL   Proc Natl Acad Sci U S A 97 (8), 3838-3843 (2000)
   PUBMED   10760255
REFERENCE   9  (bases 1 to 14623)
  AUTHORS   Ogi,T., Kato,T. Jr., Kato,T. and Ohmori,H.
  TITLE     Mutation enhancement by DINB1, a mammalian homologue of the
            Escherichia coli mutagenesis protein dinB
  JOURNAL   Genes Cells 4 (11), 607-618 (1999)
   PUBMED   10620008
REFERENCE   10 (bases 1 to 14623)
  AUTHORS   Gerlach,V.L., Aravind,L., Gotway,G., Schultz,R.A., Koonin,E.V. and
            Friedberg,E.C.
  TITLE     Human and mouse homologs of Escherichia coli DinB (DNA polymerase
            IV), members of the UmuC/DinB superfamily
  JOURNAL   Proc Natl Acad Sci U S A 96 (21), 11922-11927 (1999)
   PUBMED   10518552
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC116341.2, AC026424.5 and
            AC010245.4.
            
            On Aug 26, 2021 this sequence version replaced NM_016218.5.
            
            Summary: This gene encodes a member of the DNA polymerase type-Y
            family of proteins. The encoded protein is a specialized DNA
            polymerase that catalyzes translesion DNA synthesis, which allows
            DNA replication in the presence of DNA lesions. Human cell lines
            lacking a functional copy of this gene exhibit impaired genome
            integrity and enhanced susceptibility to oxidative damage.
            Mutations in this gene that impair enzyme activity may be
            associated with prostate cancer in human patients. [provided by
            RefSeq, Sep 2016].
            
            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 :: AF163570.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000241436.9/ ENSP00000241436.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-24                AC116341.2         23623-23646
            25-172              AC026424.5         92059-92206         c
            173-292             AC026424.5         86625-86744         c
            293-445             AC026424.5         69724-69876         c
            446-577             AC010245.4         7988-8119
            578-731             AC010245.4         11030-11183
            732-971             AC010245.4         15459-15698
            972-1096            AC010245.4         17543-17667
            1097-1263           AC010245.4         19010-19176
            1264-1296           AC010245.4         21276-21308
            1297-1393           AC010245.4         24594-24690
            1394-1565           AC010245.4         28128-28299
            1566-2522           AC010245.4         30472-31428
            2523-2565           AC010245.4         31997-32039
            2566-14623          AC010245.4         32184-44241
FEATURES             Location/Qualifiers
     source          1..14623
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5q13.3"
     gene            1..14623
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /note="DNA polymerase kappa"
                     /db_xref="GeneID:51426"
                     /db_xref="HGNC:HGNC:9183"
                     /db_xref="MIM:605650"
     exon            1..24
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            25..172
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     CDS             38..2650
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /EC_number="2.7.7.7"
                     /note="isoform 1 is encoded by transcript variant 1;
                     polymerase (DNA directed) kappa"
                     /codon_start=1
                     /product="DNA polymerase kappa isoform 1"
                     /protein_id="NP_057302.1"
                     /db_xref="CCDS:CCDS4030.1"
                     /db_xref="GeneID:51426"
                     /db_xref="HGNC:HGNC:9183"
                     /db_xref="MIM:605650"
                     /translation="MDSTKEKCDSYKDDLLLRMGLNDNKAGMEGLDKEKINKIIMEAT
                     KGSRFYGNELKKEKQVNQRIENMMQQKAQITSQQLRKAQLQVDRFAMELEQSRNLSNT
                     IVHIDMDAFYAAVEMRDNPELKDKPIAVGSMSMLSTSNYHARRFGVRAAMPGFIAKRL
                     CPQLIIVPPNFDKYRAVSKEVKEILADYDPNFMAMSLDEAYLNITKHLEERQNWPEDK
                     RRYFIKMGSSVENDNPGKEVNKLSEHERSISPLLFEESPSDVQPPGDPFQVNFEEQNN
                     PQILQNSVVFGTSAQEVVKEIRFRIEQKTTLTASAGIAPNTMLAKVCSDKNKPNGQYQ
                     ILPNRQAVMDFIKDLPIRKVSGIGKVTEKMLKALGIITCTELYQQRALLSLLFSETSW
                     HYFLHISLGLGSTHLTRDGERKSMSVERTFSEINKAEEQYSLCQELCSELAQDLQKER
                     LKGRTVTIKLKNVNFEVKTRASTVSSVVSTAEEIFAIAKELLKTEIDADFPHPLRLRL
                     MGVRISSFPNEEDRKHQQRSIIGFLQAGNQALSATECTLEKTDKDKFVKPLEMSHKKS
                     FFDKKRSERKWSHQDTFKCEAVNKQSFQTSQPFQVLKKKMNENLEISENSDDCQILTC
                     PVCFRAQGCISLEALNKHVDECLDGPSISENFKMFSCSHVSATKVNKKENVPASSLCE
                     KQDYEAHPKIKEISSVDCIALVDTIDNSSKAESIDALSNKHSKEECSSLPSKSFNIEH
                     CHQNSSSTVSLENEDVGSFRQEYRQPYLCEVKTGQALVCPVCNVEQKTSDLTLFNVHV
                     DVCLNKSFIQELRKDKFNPVNQPKESSRSTGSSSGVQKAVTRTKRPGLMTKYSTSKKI
                     KPNNPKHTLDIFFK"
     exon            173..292
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            293..445
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            446..577
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            578..731
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            732..971
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            972..1096
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            1097..1263
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            1264..1296
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            1297..1393
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            1394..1565
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            1566..2522
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            2523..2565
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     exon            2566..14623
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /inference="alignment:Splign"
     regulatory      2646..2651
                     /regulatory_class="polyA_signal_sequence"
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /note="hexamer: AGTAAA"
     polyA_site      2672
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
     regulatory      4425..4430
                     /regulatory_class="polyA_signal_sequence"
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /note="hexamer: AATAAA"
     polyA_site      4448
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /note="major polyA site"
     regulatory      5752..5757
                     /regulatory_class="polyA_signal_sequence"
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /note="hexamer: AATAAA"
     polyA_site      5776
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
     regulatory      14599..14604
                     /regulatory_class="polyA_signal_sequence"
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
                     /note="hexamer: AATAAA"
     polyA_site      14623
                     /gene="POLK"
                     /gene_synonym="DINB1; DINP; POLQ"
ORIGIN      
        1 gtagtcgcga tcctgaggta acggataagt ttataccatg gatagcacaa aggagaagtg
       61 tgacagttac aaagatgatc ttctgcttag gatgggactt aatgataata aagcaggaat
      121 ggaaggatta gataaagaga aaattaacaa aattataatg gaagccacga aggggtccag
      181 attttatgga aatgagctca agaaagaaaa gcaagtcaac caacgaattg aaaatatgat
      241 gcaacaaaaa gctcaaatca ccagccaaca gctaagaaaa gcacaattac aggttgacag
      301 atttgcaatg gaattagaac aaagccgaaa tttgagcaat accatagtgc acattgacat
      361 ggatgctttc tatgcagctg tagaaatgag ggacaatcca gaattgaagg ataaacccat
      421 tgctgtagga tcaatgagta tgctgtctac ttcaaattac catgcaagga gatttggtgt
      481 tcgtgcagcc atgccaggat ttattgctaa gaggctgtgc ccacaactta taatagtgcc
      541 ccccaacttt gacaaatacc gagctgtgag taaagaggtt aaggaaatac ttgctgatta
      601 tgatcccaat tttatggcca tgagtcttga tgaagcctac ttgaatataa caaagcactt
      661 agaagaaaga caaaattggc ctgaggataa aagaaggtat ttcatcaaaa tgggaagctc
      721 tgtagaaaat gataatccag gaaaggaagt taataaactg agtgagcatg aacgatccat
      781 ctctccacta ctttttgaag agagtccttc tgatgtgcag cccccaggag atcctttcca
      841 agtgaacttt gaagaacaaa acaatcctca aatactccaa aactcagttg tttttggaac
      901 atcagcccag gaagtggtaa aggaaattcg tttcagaatt gagcagaaaa caacactgac
      961 agccagtgca ggcattgccc caaatacaat gttagcaaaa gtatgcagtg ataagaataa
     1021 accaaatgga caataccaaa ttcttcccaa tagacaagct gtgatggact tcatcaagga
     1081 tttacccatt agaaaggttt ctggaatagg aaaagttaca gagaaaatgt taaaggccct
     1141 tggaattatt acatgtacag aactttacca acagagggca ttgctttctc tccttttctc
     1201 tgaaacatct tggcattatt tccttcatat ctccttgggt ctaggttcaa cacacctgac
     1261 gagggatgga gagaggaaaa gtatgagcgt tgagaggaca ttcagtgaga taaataaagc
     1321 ggaagagcaa tacagcctat gtcaagaact ttgcagtgag cttgctcagg atctacagaa
     1381 agaaagactt aagggtagaa ctgttaccat taagttgaag aatgtgaatt ttgaagtaaa
     1441 aactcgtgca tctacagttt catctgttgt ttctactgca gaagaaatat ttgccattgc
     1501 taaggaattg ctaaaaacag aaattgatgc tgattttcca catcccttga gattaaggct
     1561 tatgggtgtt cggatatcta gttttcccaa tgaagaggac aggaaacacc aacaaaggag
     1621 cattattggc tttttacagg ctggaaacca agccctgtca gccactgagt gtacattaga
     1681 gaaaactgac aaagataagt ttgtaaaacc tctagaaatg tctcataaga agagtttctt
     1741 tgataaaaaa cgatcagaaa ggaaatggag tcaccaagat acatttaaat gtgaagccgt
     1801 gaataaacaa agtttccaga catcacaacc attccaagtt ttaaagaaga agatgaatga
     1861 gaatttggaa atatcagaga attcagatga ctgtcagata cttacctgtc ctgtttgctt
     1921 tagggctcaa gggtgcatca gtctggaagc cttgaataaa catgtagatg aatgtcttga
     1981 tggaccttca atcagtgaaa actttaaaat gttctcgtgt tcacatgttt ctgctaccaa
     2041 agttaacaag aaagaaaatg ttcctgcttc ttcactttgt gagaagcaag attatgaagc
     2101 ccatccaaaa attaaagaaa tatcttcagt agattgtata gctttagtag atactataga
     2161 taactcatct aaagcagaaa gcatagatgc tttaagtaat aagcatagca aggaagaatg
     2221 ttctagtctc ccaagcaagt cttttaatat tgaacactgt catcagaatt cttcttctac
     2281 tgtttcattg gaaaacgaag atgttggatc atttagacaa gaataccgcc agccttactt
     2341 atgtgaagtg aaaacaggcc aagctctagt ttgtcctgtt tgtaacgtag aacaaaagac
     2401 ttcagatcta accctgttca atgtgcatgt ggatgtttgc ttaaataaaa gttttatcca
     2461 agaattaaga aaggataaat ttaacccagt taatcaaccc aaagaaagct ccagaagtac
     2521 tggtagctca agtggagtac agaaggctgt aacaagaaca aaaaggccag gattgatgac
     2581 aaagtactca acatcaaaga aaataaaacc aaacaatccc aaacataccc ttgatatatt
     2641 ttttaagtaa acattgaaca ttttatcatt aatttttaat tgaaactagt tattttataa
     2701 tcaatgaatt tgttctttct gattttaagt ttgcagattt atttagtgaa ggcaagtgca
     2761 ataatccttc ctcagatgat gtttgctttt ctaagataca tatactgatt ctgtgtatct
     2821 tttttataac catgagaatt ttacttccat tatacatcaa ttggaaatca atcctgttaa
     2881 gagataattc ttaaaaggga aattaggaat gggataagaa ggtgattttt ttattatttt
     2941 tatactgaat ataaaaacat ttgtaagggc tctcaaagat tcacacatgc ctatattatc
     3001 ataagaattt ttcagcactt aactactttg ttggcattga tcctagtgtc tttaaatact
     3061 tcatgagcat tcataattaa aatttatctt aagttctatg aagagtatta atgtaactag
     3121 cataagtggt tttcttcagg aaaataaata tcacagtatt atctgtgtta aaatggtttt
     3181 tgcctaaaat ataattttta atttggcttt tcttatttaa aattccatta tcttatgaat
     3241 aagcacttga atcagttttt aaaatattta gtctaagatg attcaaagta gttttatttt
     3301 aatacaggac ttttaaatgg cagtatttca tttcttgtca attatgttgg tactttccac
     3361 aaatctataa agaaggataa attgtaccat cattttatta taatcctcaa gagaaaatgt
     3421 gtaattcaaa agattaatgt gtattaaaac acattatgta tcttagttac atttctatca
     3481 gtacttttat taatatttgt gaaagaagac agcttaatag tagttagctt aagtagtttc
     3541 tccaagtact tttgtgctat caatgagttc ttctcaaaaa ataattagtt aggccaggca
     3601 caatggctca cacctgtaat gccagccctt tgggaggccg aatgggcaga tcacttgagg
     3661 tcaggagttt gagaccagcc tcgccaacat ggtgagaccc tgtctctact aaaacgataa
     3721 aaaaaaaaaa aaaattagcc aggcttggtg gcacacgcct gtaatcccag ctactcagat
     3781 ggctgaggca ggagaactac ttgaacctgg gaggtcaaag ctgcagtcag ccaagatctt
     3841 gccactgtac tccagcctga agagcgagac tctgtctcaa taatataata atagttatta
     3901 tttaattgca acatgaagtt ggaagccatt ttctgttact tctttaagga gctaaatctt
     3961 ttatattttt gttttctctc cccttgcgtt tcatatttta gcttatgatc taaatatata
     4021 ttttgtatat tataatattt taggaatagc ttaattaaga actcacagac tttgacaaag
     4081 tggtaactag acttttaatt actagattct tcaaattagg cttaatgcct gctagcatgc
     4141 caatccaatc ccatgactga tgttattata cactatggca aatacaaagt tgtagtatta
     4201 tggttcttga tggtgtgatt tacttatgta aattatgtac aaatttaagt tcaatgaaac
     4261 actgatttaa tgtactgaaa ggtaaatagt accatagtga attattttct gtcttgcctt
     4321 aggtttattt ttattatctt caatattaga ataaatgcta aattattttc atttaaggat
     4381 ttatgtagtt gaatattatc atttagtaat atttaatcat ttgaaataaa atttaaagct
     4441 ttaattgatc taatagagat ggttttctac ttttccactc ttcctccctc ttatgccttc
     4501 acttttgttt tctgtgccca gaattttctt cacattcttt actacctgtt ttgtctatta
     4561 tatccaaccc attttctttt tattataatt ttgatttggg gcatttgaag aaaatacagc
     4621 aaaactacaa gaactggtaa taagcatgca taatctcacc tacttagtga acctaatata
     4681 aacctaatat aaagaaccac cgtatttgca atatatataa ctggtgaaaa actagtgtcc
     4741 agaatatata aatgatccct atgaatcagt aagaaaaaga cagtcaatag aaatttggac
     4801 aaaagacttt atatggcatt tcaagtgaaa ggaaatccag atgaccaaga aacatgaaaa
     4861 tattcccagc catattaata tttgagaagt aaaaaataaa actacaagga ggtattacat
     4921 ctttacctta tttgcaaaaa tgaaatgatc taatgatact aagttttggt gatgatgtca
     4981 gctcttacat tgaaaacaat cactgtggaa aaatttgtcc ctcagtaaat ttaaagataa
     5041 acatgctcaa aacctagcaa ttgcactctg aagtatacat ctttgcaggt tatctttcat
     5101 tacagttatt tttttccctg tcaggaccct aactaataca atgccttggg aaaactaatg
     5161 aacatgtatc ctaggaagca tgtacaagaa agttcttccc agtcaggaag gtggccaaga
     5221 aaaaaatttt ttaatgttca tagcagcact gcaatatcca aaagttagaa atgaaccaaa
     5281 tattcagcaa tggtagaatg gttaaattgt accatggcat ttatattgaa acagtagaat
     5341 tctacacagt ggtgaaaatg aaggaaatag ctaaccacaa catagatgaa tatcacagac
     5401 atagcataga gcaaaagaag caaatcacag aaggatgcca tcaacatgat tccatttgta
     5461 taaagtttaa aacagtataa actgaacaac tatattgttt taagggtata tagttatata
     5521 tatgagatac aactgtaaag aaaagcaagt gttttgctgt ccccagaacc agaataatga
     5581 tttcctctgt ggagaagtac agcagtgtga ttggggagtg gcacctggtg cttctgggat
     5641 gctggcaatg ttctatttct tgtcttgggt ggtgattgca tggatgttca cttttaaaat
     5701 actctttata catatatatt ttatatattc ttgttcatat ataaccttta taataaagag
     5761 aaaaaaatgg caaaaactgc tttcgttaac aagatgatat tttcctccaa ctctgcaggc
     5821 tagctaattt caatcgagaa aaaaatacat ttttttcttc tagaaccttg ctgaacacag
     5881 caagaaagag ccatcccatg caaaattttt agtttttctc ctagcatttc ccctaaggct
     5941 acagcctcaa tcagtatttg gtcttctttc caaagacagc tgttgacagt tagaccaaat
     6001 atttttttgc cgtttgtgat ggttaatatt gagtgtcaac ttgattggat taaatgatgc
     6061 aaaatattgt tcctgggtgt gtctgtgagg gtattgccaa agaagattaa catttgagtc
     6121 agtgggctca agaagcagat ccaccctcaa tctggttgtg caccatctaa tcaactgcca
     6181 gcatagctag gataaaagca ggcagaggaa ggtggaagga ctacactggc taagtcttct
     6241 ggcctccgtc tttctcctgt gctgcatgtc ttctgccctt gaacatcaga ctccaagttc
     6301 ttcagctttt ggactcttgg acttccacca gtgatttgcc agggactatc aggccttcag
     6361 ccacagactg aagggctgca ccatctgctt gtctgctttt gaggttttgg gactcagact
     6421 ggcttcctgg cttctcagct tgcagactgt gggacttcac cttgtgattg tgtgagtcaa
     6481 ttttcctaag aaactcccct tcatatatac atctattagt tctgtccctc tagaggaccc
     6541 taatacacca ccaaacaagt caccagtttt ccagtctgtg gtatttgtgt ccccactccc
     6601 taaattcttc tctccaaccc taagtcaatt tgttatatta ggctttgtta tttgcagtac
     6661 cctatttctg tatcagttca gtcacaagct tcctggtgcc tcttccttgt tgagtcacat
     6721 ggggacatgc ttaattctcc cagaaatgtg tgacagcatg tgcaaaatat tgccaaccaa
     6781 ggaagctcaa ccaatccttg gtgtccaagg tgtttactgg aagtcagtca cataggcatg
     6841 catcacccat gtgactgacc ttacccgttg agtctcaaga ccccaggggt gtagtgatac
     6901 ctcatggccc agggcttcag ccattcaaaa acagacattc gccatgattc atactgttag
     6961 cataaactat ctcgtcaaac taacaaaatg cagcccaagg cctcaggcat actagaacac
     7021 tattatcaaa ctggaaattc cacgagctca ggtcatttcc caggagctag tcaaggaagg
     7081 gccagtacgt gaagacacct ctctttgaaa agtgcagggc tggagtaacc tgaggctgct
     7141 aggttaaccc tttactgcat taatgtcaaa ttattagaat tgtattcaaa taaaatataa
     7201 aaaagaaaga tcacttagag taactttttc ctgcctcact tgaataatgc agagacactt
     7261 caaattcgta acatgtttag ggggtctcaa ggaggatggg ctatgcgttt tgaatatatg
     7321 catataaaac aacaaatgac ataggcctaa taatttcttt gcatgtgtat aatcctctct
     7381 tcaatgtaat tcaaaggtct cttttttaat atcagtcttt acattgtccc tgtaatatag
     7441 agctatacac ctttcctcaa tcttttgtga tagtaggaaa agtagcatta taagaagtat
     7501 ttataaattt aattcactcc accagaaatg ttttatttta aagttagcat gggacttgtg
     7561 gtatccgcaa ggtcagtgtc cccactgaag aagtggcctt ctagagtaag aagtttcagc
     7621 atcaacatgg gtaatggaag ccatataaca gaacttaaga aggaactttg tgctaagaaa
     7681 atgtagacag tggttatagg catatatgta agaaggctgt aagttaaagg caagagagat
     7741 gtagcaatta ataggagata ttttttctgc catcattaac aaatgtattt gtttactact
     7801 ccttactttt taactcatcc accttgtatc cactgctacc tctgccaacc ctgtatctgt
     7861 tactgaattc tgtctactct tgtagggcct cttgaaaatg aaaatatcca tttgtttcca
     7921 tctcttttgt caagccctta tcagttgtct aaactcttga ctttccaact gatttgtcag
     7981 ttttccctgc tctaaaccat cttatgcatt ttttacagat tagctataaa cagcattccc
     8041 ataatagcac tctcatgtca aaaaaaaaaa aaaagcagtt ttcaaaagct ctcaactgtc
     8101 tccaagattt agcagtggaa tgagtaggaa aagggagtga tttttagtgt atgattattt
     8161 atgtggtgta aatgctccca ccatgacaga tttcaagtta tgtgatgtca gccagttcac
     8221 aaaattcctg aaactttaac agctcttgca agccaataca agctagctcc tatatatcac
     8281 tgtccatgat gcactctaaa cactggcttg gcattcaggg tttcctgaac agaccaagct
     8341 gtttctcctt tctggcatct gtgctccatt gttccctctg cccagaatat gcttcctgaa
     8401 tgcccctttt ctctctccca cctacataat tactcatctt tcaactcagc tcaagggcca
     8461 ccttcagaaa agtgttcctt gccctctgga aaaattgatc agtcactatt ttttgctcct
     8521 gtttccctac aaagaccctg aaacattctt tgcatggccc ccgatgttgg tttctcccta
     8581 ccagattgta ggccccaaga gatcctgggc tatctttcac ttatctctga attccaagta
     8641 tgaagtgtat ggcctggcac acagtagata cggagagtca tttgttgaca tgtaaatgaa
     8701 taaatagtat gtgtccaaaa gtgtttacta ctatcttatt gtttttatct gggaagacag
     8761 aatggtggct aagggctgct gtcacactgg gtcctaaaga gtggacattc cagaaagaga
     8821 caattgcatt tatttccctt tattagataa tggcttgctt tatacatgtt ttattattat
     8881 actgtgtcgt tttggagtgg cttgggagta tttggaagaa ggcttaaaat atgactatta
     8941 acctggggct aaaaaaaact gtttttgagg aaatatttca tttaaaaaaa tcatacctgg
     9001 tgtacctggt gctgaactgt tgtttttaga gacaaggtct caccgtcacc caggctgaaa
     9061 tacattgtca tgatcataac tcactgcagc ctggaactct tgggatcaag atcctctcat
     9121 cgcagcttcc caagtagctg ggactacagg ctggtgccat gatgcccagc taagtttttg
     9181 tatttttttg ttgagatagg atcttgctat gtggcctaga ttggtcttga actcctggct
     9241 tcaagcattc ctccttcctc agtctcccaa agctctggga ttaacaggca tcagccacca
     9301 tgcctggccc tggtactgaa ttttctttga agtaaggttc cattttgaaa agcagtgata
     9361 tatttgaaca cactttgtgt tggtaggatt ttagtaaacc tcacagagag gtgatgctta
     9421 tttccctgga gaaaaaactg ttctttaatt gtataattaa ggactaatcg cttttgcttt
     9481 gtaatacata actgaattaa gttgttcaag aaaaactcaa atgacatcat ggtgactatt
     9541 ggcaacatga ttccatttat taagcaaacc ataatattga actgttcccc ttaccagtac
     9601 gaggtaattg tgatagtctt actttgtaac tgctgctgtc tacagaatgc tcagggagat
     9661 taaagataat tcagaggcaa atggtactaa cccttctaac ctcagcctgt aaagtgtagt
     9721 atgatttcaa actctttcct gtatacacat acacacacac acacacacac acacacacac
     9781 acacacacac tacctctgcc aaccacatac ctatcattga gttctgtcta ctcttgtagg
     9841 gcctcttgaa aacacttctt tccatttctt ttatcaggtt cttatcagtt gtctaatatc
     9901 tggccttcta actcattgct tagctttcac cagtttcttt ccctgcttta gatcatcttg
     9961 tgcatttttg tagacaatac tttcctaata tcactcatgg tcttgggtgt ctatggagag
    10021 agtgagagag agagagattc cctaaattgg agacaaaaag gaaaaaaaag ttgggtcact
    10081 tctaggatca aatctagttc tcttttatga aggctcaaaa gttttttccc tctcagaata
    10141 tgctaaactt caaatgtgat ctctgaaacc atccgcaagt ctgagatacg ccatggtttt
    10201 ttgggttttg ctagcaattc tgggcagaga tcctggttgt ccttcaacat tctacttttc
    10261 tgccatatta ttagaatttt agcttggcac atgatcaccc agaatagact aatgtatttc
    10321 atcaattctt tataaaccac taagaaataa tacctaagat agggagtcta acaggttacc
    10381 actgcataaa tatgggacac caaggtttat accttcagag caaggataaa ggagaaatct
    10441 tccatgaaga aagagggagc aaagtgtagg ggtgggttgc ccctacacac ctgtgggtgt
    10501 ttctcgtaag gtgggacgag agatttggaa aagaaaaaga cacagagaca aagtatagag
    10561 aaagaaataa ggggaaccgg ggaaccagcg ttcagcatat ggaggatccc gccagcctct
    10621 gagttccctt agtatttatt gatcatctgt gggtgtttct caaagagggg gatgtgtcag
    10681 ggtcacaaga caattgtggg gagagggtca gcagacaaac acgtgaacaa aggtcttggc
    10741 atcatagaca atgtaaagga ttaagtgctg tgcttttaga tatgcataca cataaacatc
    10801 tcagtgcttt acaaagcagt attgctgccc gcaggtccca cctccagccc taaggcggtt
    10861 tttccctatc tcagtagatg gagcatacaa tcgggtttta taccgagaca ttccattgcc
    10921 cagggacagg caggagacag atgccttcct cttgtctcaa ctgcaagagg cattccttcc
    10981 tcttttacta atcctcctca gcacagaccc tttacgggtg tcgggctggg ggacggtcag
    11041 gtctttccct tcccacgagg ccatatttca gactatcaca tggggagaaa ccttggacaa
    11101 tacctggctt tcctaggcag aggtccctgc ggccttccgc agtttttgtg tccctgggta
    11161 cttgagatta gggagtggtg atgactctta aggagcatgc tgccttcaag catctgttta
    11221 acaaagcaca tcctgcaccg cccttaatcc attcaactct gagttgacac agcacatgtt
    11281 tcagagagca cggggttggg ggtaaggtca cagaatctca aggcagaaga atttttctta
    11341 gtacataaca aaatggagtc tcctatgtct acttctttct acacagacac agtaacaatc
    11401 tgatctctct tgcttttccc cacagcaaag caatttgcat gctcagcctt ggcactggtt
    11461 ggaaggaggg actgccagtg agaatttgaa ccataaacca gtacacatgt aggcttgtaa
    11521 tctgaattca cacaaatggt atcatcctaa agagctcaag cagaaaatgt aattaaagtg
    11581 aggttagtat tgcccctagt gactggcaga agcatatgca aatcctctat ggaagaactc
    11641 aacttcaatt caggcagaca acttagtatc tcaattaaaa agatgtgata atgtgaaaaa
    11701 taggtgttac agaattgatg actacaatgt atctcccatc cttgaagctc acaccctccc
    11761 agctaggggt agccatgtga ctgagttttg actaatggga tataaaagga agtactggcc
    11821 gggtgcggtg tctcacgcct gtaatctcag cactttggga ggccaaggcg ggtggatcac
    11881 ctgaggtcag gagttcgaga ccagcctggc caagatggtg aaaccccgtc tctactcaaa
    11941 atacaaaaaa gtagctgggc gtggtggcac acacttgtga tcccagctac tcaggaggct
    12001 gaggcaagag aatcgcttga acccgggaga cggaggttgc agtgagctga gattgcacca
    12061 ctgcactcca acctgggtga caaagcgaga ccttgtctca aaaaaaaaaa aaaaaaaagg
    12121 aagtactgtg tgtggttgct tctgggaacc ttcctttctt gcagctgtag cattctgttt
    12181 gcctcttctt tctatttctc tgttccatcc tgctgcctgg aagcagatgc tgccgtttac
    12241 acctgaacat aagggttgca cagggggatg gtagagtagt gggctgcagg ggctgattct
    12301 tggggctttg taaaacagag acatatcagc actggcctgc acactttgag actttcacaa
    12361 gaaacaaatt aaaaaattgt ttaagccata gttacttggg ttttcctatt aattatagct
    12421 gaatcctagc tgataaagga cataaagatt attaagacat gtttgtcctc aaaaaatgga
    12481 gagccacccc agggacagtt tctattcaat gtagggaggg ctataataga tgaatataca
    12541 aagtgggagt ctagggagaa atcgtctggt agaggagggc aaagagaaat ctaggaagat
    12601 gtttttaaaa atatggaatc cttgaacagg acctggtttt aaaggtttac ttcagaattg
    12661 aacatatttt tttagtctag acctttaggg gaaaaactta aagctttcag gactcaaaga
    12721 caagttactg ttcccatggc taaattgcat tccatattta tttgacaaat acttattgca
    12781 ggtcgggtac tgttttagcc actggagatg cagtaagaaa cttaattaat tttttttttt
    12841 tttgagacag agtcttgctc tgtcacccag gttggaatgc agtgacatga taacagcttg
    12901 ctgcagcctt gacctccgtg gctcaggcca tactcccatc tcagcttccc aagtagctaa
    12961 gactacaggt ctgccccacc accaccagct aatttttaaa ttttttgtgg agactggagt
    13021 ctcactaagt tgcccaggtt ggcctcaaac tcctggcctc aagccatcct cccacttcgg
    13081 cctctcaaat tgctgggatt ataggcatga gacaccacgc ctggcccaac aaagttttaa
    13141 aaatcactgt atttatgaag tttacattct agttgtggaa accgacacta aacaaataga
    13201 catttcagtg gtaagtgtta caaaggaaag agacaacagc ataagggaat ggaacatgaa
    13261 ggtaggggac acttttagaa taagatgatc cgagaaggct cctctgagga agtgacattt
    13321 aacctgaaac cttaatgata cgaaggatca aaactatttt aaaaattcgg aagtggaggt
    13381 gggggagaga agttctaggc aaagggagga aatagaagct gatggctctc caccaggaaa
    13441 cagtggatga agaatggaga agaattgtag ggcccaagat cagagagatg agtagggcca
    13501 gatcatgtgg gcaagctttt atgtattagc acgcttagaa ttaatattct gcttgagaac
    13561 taacctgata tttgaaacag agtgaaaaag aaaatacctc ccacagtata cttcatagct
    13621 tcttatttag cccaagctgt cagggaaata aagtccagct atggctaagt ttcacataat
    13681 gcactgcttt ggagtttttg tctcatctgt tagagtaaga taagtaccac atactattat
    13741 aaggctatat agcataaaat gatgatgcat tttctcctgt cattgataag aggatttttt
    13801 taaaagtaaa tttcttggtt tagaatttga aagcagtttc aaacttggat aacacaattc
    13861 agatcttttt ttaaaattat tttttattta tattaaaaaa aaattttttt tttgagatag
    13921 ggtctggctc tatcacgcag actggcacac agtggcacaa tcttggctca ttgcaacctc
    13981 tgcctcccag gctgaagcca tcctcccacc tcagcctccc aagtagctgg gactacaggc
    14041 atgcaccacc atgcctggct aatttttgta gagagggggt ctcactttgt tacccagact
    14101 gggagatttt tctgtacttg gctgtatgct ttccattgat ctgctgctgt tttcactatt
    14161 attccttctt ttgtgtgggt attttctttt gatttttaga attttacttg taaacatgct
    14221 acatatacat ataatttggt gccctgtttt tccatttaca tattatactt tccatattag
    14281 tacattgtct gatatttctg cataatactc aattcaactt acctgctatt gtttttatca
    14341 tatctctatt acaaacatta ggcccatttc ccttttttaa aagaggaaag tttgaggtta
    14401 tgggcggtgt tctgataaaa taaataatat tttgtcatgt ttgttttttc attgattagg
    14461 aaacattgtt ttgaatttaa tgcctcaaat ttggtgcaca ataatttgaa gggaaaaact
    14521 gacaagtttg aaatgaacat tgatattaca taatttacat taaaatgata catcttttgt
    14581 aaatttgtaa gaagaataaa taaatgaaaa cctgattacc ttt
//
