LOCUS       NM_006231               7823 bp    mRNA    linear   PRI 07-FEB-2025
DEFINITION  Homo sapiens DNA polymerase epsilon, catalytic subunit (POLE),
            mRNA.
ACCESSION   NM_006231
VERSION     NM_006231.4
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 7823)
  AUTHORS   Shah,S.M., Demidova,E.V., Ringenbach,S., Faezov,B., Andrake,M.,
            Gandhi,A., Mur,P., Viana-Errasti,J., Xiu,J., Swensen,J., Valle,L.,
            Dunbrack,R.L. Jr., Hall,M.J. and Arora,S.
  TITLE     Exploring Co-occurring POLE Exonuclease and Non-exonuclease Domain
            Mutations and Their Impact on Tumor Mutagenicity
  JOURNAL   Cancer Res Commun 4 (1), 213-225 (2024)
   PUBMED   38282550
  REMARK    GeneRIF: Exploring Co-occurring POLE Exonuclease and
            Non-exonuclease Domain Mutations and Their Impact on Tumor
            Mutagenicity.
            Erratum:[Cancer Res Commun. 2024 May 31;4(5):1398. doi:
            10.1158/2767-9764.CRC-24-0280.. PMID: 38819318]
REFERENCE   2  (bases 1 to 7823)
  AUTHORS   Ostroverkhova,D., Tyryshkin,K., Beach,A.K., Moore,E.A.,
            Masoudi-Sobhanzadeh,Y., Barbari,S.R., Rogozin,I.B., Shaitan,K.V.,
            Panchenko,A.R. and Shcherbakova,P.V.
  TITLE     DNA polymerase epsilon and delta variants drive mutagenesis in
            polypurine tracts in human tumors
  JOURNAL   Cell Rep 43 (1), 113655 (2024)
   PUBMED   38219146
  REMARK    GeneRIF: DNA polymerase epsilon and delta variants drive
            mutagenesis in polypurine tracts in human tumors.
REFERENCE   3  (bases 1 to 7823)
  AUTHORS   Tang,M., Yin,S., Zeng,H., Huang,A., Huang,Y., Hu,Z., Shah,A.R.,
            Zhang,S., Li,H. and Chen,G.
  TITLE     The P286R mutation of DNA polymerase epsilon activates
            cancer-cell-intrinsic immunity and suppresses endometrial
            tumorigenesis via the cGAS-STING pathway
  JOURNAL   Cell Death Dis 15 (1), 69 (2024)
   PUBMED   38238314
  REMARK    GeneRIF: The P286R mutation of DNA polymerase epsilon activates
            cancer-cell-intrinsic immunity and suppresses endometrial
            tumorigenesis via the cGAS-STING pathway.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 7823)
  AUTHORS   Zheng,S., Donnelly,E.D. and Strauss,J.B.
  TITLE     Race, Prevalence of POLE and POLD1 Alterations, and Survival Among
            Patients With Endometrial Cancer
  JOURNAL   JAMA Netw Open 7 (1), e2351906 (2024)
   PUBMED   38231514
  REMARK    GeneRIF: Race, Prevalence of POLE and POLD1 Alterations, and
            Survival Among Patients With Endometrial Cancer.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 7823)
  AUTHORS   Kitazono,I., Akahane,T., Yokoyama,S., Kubota,E., Nishida-Kirita,Y.,
            Noguchi,H., Murakami,M., Yanazume,S., Kobayashi,H. and Tanimoto,A.
  TITLE     Cervical Cytology Preserves Histologically Detected Surface
            Epithelial Slackening, Unique to the POLE Mutation-subtype in
            Endometrial Cancer
  JOURNAL   In Vivo 38 (1), 321-333 (2024)
   PUBMED   38148087
  REMARK    GeneRIF: Cervical Cytology Preserves Histologically Detected
            Surface Epithelial Slackening, Unique to the POLE Mutation-subtype
            in Endometrial Cancer.
REFERENCE   6  (bases 1 to 7823)
  AUTHORS   Mozzherin,D.J. and Fisher,P.A.
  TITLE     Human DNA polymerase epsilon: enzymologic mechanism and gap-filling
            synthesis
  JOURNAL   Biochemistry 35 (11), 3572-3577 (1996)
   PUBMED   8639508
REFERENCE   7  (bases 1 to 7823)
  AUTHORS   Szpirer,J., Pedeutour,F., Kesti,T., Riviere,M., Syvaoja,J.E.,
            Turc-Carel,C. and Szpirer,C.
  TITLE     Localization of the gene for DNA polymerase epsilon (POLE) to human
            chromosome 12q24.3 and rat chromosome 12 by somatic cell hybrid
            panels and fluorescence in situ hybridization
  JOURNAL   Genomics 20 (2), 223-226 (1994)
   PUBMED   8020968
REFERENCE   8  (bases 1 to 7823)
  AUTHORS   Kesti,T., Frantti,H. and Syvaoja,J.E.
  TITLE     Molecular cloning of the cDNA for the catalytic subunit of human
            DNA polymerase epsilon
  JOURNAL   J Biol Chem 268 (14), 10238-10245 (1993)
   PUBMED   8486689
REFERENCE   9  (bases 1 to 7823)
  AUTHORS   Popanda,O. and Thielmann,H.W.
  TITLE     The function of DNA polymerases in DNA repair synthesis of
            ultraviolet-irradiated human fibroblasts
  JOURNAL   Biochim Biophys Acta 1129 (2), 155-160 (1992)
   PUBMED   1730053
REFERENCE   10 (bases 1 to 7823)
  AUTHORS   Wang,T.S., Hu,S.Z. and Korn,D.
  TITLE     DNA primase from KB cells. Characterization of a primase activity
            tightly associated with immunoaffinity-purified DNA
            polymerase-alpha
  JOURNAL   J Biol Chem 259 (3), 1854-1865 (1984)
   PUBMED   6693436
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from L09561.1, CX782956.1 and
            BC011376.1.
            
            On Aug 31, 2019 this sequence version replaced NM_006231.3.
            
            Summary: This gene encodes the catalytic subunit of DNA polymerase
            epsilon. The enzyme is involved in DNA repair and chromosomal DNA
            replication. Mutations in this gene have been associated with
            colorectal cancer 12 and facial dysmorphism, immunodeficiency,
            livedo, and short stature. [provided by RefSeq, Sep 2013].
            
            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 :: L09561.1, U49356.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000320574.10/ ENSP00000322570.5
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-3182              L09561.1           18-3199
            3183-3330           CX782956.1         614-761
            3331-6736           L09561.1           3348-6753
            6737-7823           BC011376.1         808-1894
FEATURES             Location/Qualifiers
     source          1..7823
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q24.33"
     gene            1..7823
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /note="DNA polymerase epsilon, catalytic subunit"
                     /db_xref="GeneID:5426"
                     /db_xref="HGNC:HGNC:9177"
                     /db_xref="MIM:174762"
     exon            1..89
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     CDS             28..6888
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /EC_number="2.7.7.7"
                     /note="3'-5' exodeoxyribonuclease; DNA polymerase II
                     subunit A; polymerase (DNA directed), epsilon, catalytic
                     subunit; DNA polymerase epsilon catalytic subunit protein;
                     polymerase (DNA) epsilon, catalytic subunit"
                     /codon_start=1
                     /product="DNA polymerase epsilon catalytic subunit A"
                     /protein_id="NP_006222.2"
                     /db_xref="CCDS:CCDS9278.1"
                     /db_xref="GeneID:5426"
                     /db_xref="HGNC:HGNC:9177"
                     /db_xref="MIM:174762"
                     /translation="MSLRSGGRRRADPGADGEASRDDGATSSVSALKRLERSQWTDKM
                     DLRFGFERLKEPGEKTGWLINMHPTEILDEDKRLGSAVDYYFIQDDGSRFKVALPYKP
                     YFYIATRKGCEREVSSFLSKKFQGKIAKVETVPKEDLDLPNHLVGLKRNYIRLSFHTV
                     EDLVKVRKEISPAVKKNREQDHASDAYTALLSSVLQRGGVITDEEETSKKIADQLDNI
                     VDMREYDVPYHIRLSIDLKIHVAHWYNVRYRGNAFPVEITRRDDLVERPDPVVLAFDI
                     ETTKLPLKFPDAETDQIMMISYMIDGQGYLITNREIVSEDIEDFEFTPKPEYEGPFCV
                     FNEPDEAHLIQRWFEHVQETKPTIMVTYNGDFFDWPFVEARAAVHGLSMQQEIGFQKD
                     SQGEYKAPQCIHMDCLRWVKRDSYLPVGSHNLKAAAKAKLGYDPVELDPEDMCRMATE
                     QPQTLATYSVSDAVATYYLYMKYVHPFIFALCTIIPMEPDEVLRKGSGTLCEALLMVQ
                     AFHANIIFPNKQEQEFNKLTDDGHVLDSETYVGGHVEALESGVFRSDIPCRFRMNPAA
                     FDFLLQRVEKTLRHALEEEEKVPVEQVTNFEEVCDEIKSKLASLKDVPSRIECPLIYH
                     LDVGAMYPNIILTNRLQPSAMVDEATCAACDFNKPGANCQRKMAWQWRGEFMPASRSE
                     YHRIQHQLESEKFPPLFPEGPARAFHELSREEQAKYEKRRLADYCRKAYKKIHITKVE
                     ERLTTICQRENSFYVDTVRAFRDRRYEFKGLHKVWKKKLSAAVEVGDAAEVKRCKNME
                     VLYDSLQLAHKCILNSFYGYVMRKGARWYSMEMAGIVCFTGANIITQARELIEQIGRP
                     LELDTDGIWCVLPNSFPENFVFKTTNVKKPKVTISYPGAMLNIMVKEGFTNDQYQELA
                     EPSSLTYVTRSENSIFFEVDGPYLAMILPASKEEGKKLKKRYAVFNEDGSLAELKGFE
                     VKRRGELQLIKIFQSSVFEAFLKGSTLEEVYGSVAKVADYWLDVLYSKAANMPDSELF
                     ELISENRSMSRKLEDYGEQKSTSISTAKRLAEFLGDQMVKDAGLSCRYIISRKPEGSP
                     VTERAIPLAIFQAEPTVRKHFLRKWLKSSSLQDFDIRAILDWDYYIERLGSAIQKIIT
                     IPAALQQVKNPVPRVKHPDWLHKKLLEKNDVYKQKKISELFTLEGRRQVTMAEASEDS
                     PRPSAPDMEDFGLVKLPHPAAPVTVKRKRVLWESQEESQDLTPTVPWQEILGQPPALG
                     TSQEEWLVWLRFHKKKWQLQARQRLARRKRQRLESAEGVLRPGAIRDGPATGLGSFLR
                     RTARSILDLPWQIVQISETSQAGLFRLWALVGSDLHCIRLSIPRVFYVNQRVAKAEEG
                     ASYRKVNRVLPRSNMVYNLYEYSVPEDMYQEHINEINAELSAPDIEGVYETQVPLLFR
                     ALVHLGCVCVVNKQLVRHLSGWEAETFALEHLEMRSLAQFSYLEPGSIRHIYLYHHAQ
                     AHKALFGIFIPSQRRASVFVLDTVRSNQMPSLGALYSAEHGLLLEKVGPELLPPPKHT
                     FEVRAETDLKTICRAIQRFLLAYKEERRGPTLIAVQSSWELKRLASEIPVLEEFPLVP
                     ICVADKINYGVLDWQRHGARRMIRHYLNLDTCLSQAFEMSRYFHIPIGNLPEDISTFG
                     SDLFFARHLQRHNHLLWLSPTARPDLGGKEADDNCLVMEFDDQATVEINSSGCYSTVC
                     VELDLQNLAVNTILQSHHVNDMEGADSMGISFDVIQQASLEDMITGGQAASAPASYDE
                     TALCSNTFRILKSMVVGWVKEITQYHNIYADNQVMHFYRWLRSPSSLLHDPALHRTLH
                     NMMKKLFLQLIAEFKRLGSSVIYANFNRIILCTKKRRVEDAIAYVEYITSSIHSKETF
                     HSLTISFSRCWEFLLWMDPSNYGGIKGKVSSRIHCGLQDSQKAGGAEDEQENEDDEEE
                     RDGEEEEEAEESNVEDLLENNWNILQFLPQAASCQNYFLMIVSAYIVAVYHCMKDGLR
                     RSAPGSTPVRRRGASQLSQEAEGAVGALPGMITFSQDYVANELTQSFFTITQKIQKKV
                     TGSRNSTELSEMFPVLPGSHLLLNNPALEFIKYVCKVLSLDTNITNQVNKLNRDLLRL
                     VDVGEFSEEAQFRDPCRSYVLPEVICRSCNFCRDLDLCKDSSFSEDGAVLPQWLCSNC
                     QAPYDSSAIEMTLVEVLQKKLMAFTLQDLVCLKCRGVKETSMPVYCSCAGDFALTIHT
                     QVFMEQIGIFRNIAQHYGMSYLLETLEWLLQKNPQLGH"
     exon            90..231
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            232..312
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            313..357
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            358..450
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            451..605
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            606..747
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            748..828
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            829..936
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            937..1047
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1048..1133
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1134..1253
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1254..1386
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1387..1500
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1501..1713
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1714..1821
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1822..1950
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1951..2053
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            2054..2200
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            2201..2346
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            2347..2495
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            2496..2588
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            2589..2733
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            2734..2891
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            2892..3087
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            3088..3302
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            3303..3405
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            3406..3486
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            3487..3609
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            3610..3822
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            3823..4032
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            4033..4176
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            4177..4317
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            4318..4471
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            4472..4578
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            4579..4755
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            4756..4979
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            4980..5200
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            5201..5405
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            5406..5579
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            5580..5705
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            5706..5838
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            5839..6031
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            6032..6163
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            6164..6357
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            6358..6558
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            6559..6684
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            6685..6774
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     exon            6775..7823
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /inference="alignment:Splign:2.1.0"
     polyA_site      7823
                     /gene="POLE"
                     /gene_synonym="CRCS12; FILS; IMAGEI; POLE1"
                     /note="major polyA site"
ORIGIN      
        1 gaagcagagg tggtagccaa cggctccatg tctctgagga gcggcgggcg gcggcgcgcg
       61 gacccaggcg cggatggcga ggccagcagg gatgatggcg ccacttcctc agtttcggca
      121 ctcaagcgcc tggaacggag tcagtggacg gataagatgg atttgcggtt tggttttgag
      181 cggctgaagg agcctggtga gaagacaggc tggctcatta acatgcatcc taccgagatt
      241 ttagatgaag ataagcgctt aggcagtgca gtggattact actttattca agatgacgga
      301 agcagattta aggtggcttt gccctataaa ccgtatttct acattgcgac cagaaagggt
      361 tgtgagcgag aagtttcatc ttttctctcc aagaagtttc agggcaaaat tgcaaaagtg
      421 gagactgtcc ccaaagagga tctggacttg ccaaatcact tggtgggttt gaagcgaaat
      481 tacatcaggc tgtccttcca cactgtggag gatcttgtca aagtgaggaa ggagatctcc
      541 cctgccgtga agaagaacag ggagcaggat cacgccagcg acgcgtacac agctctgctt
      601 tccagtgttc tgcagagggg cggtgtcatt actgatgaag aggaaacctc taagaagata
      661 gctgaccagt tggacaacat tgtggacatg cgcgagtacg atgttcccta ccacatccgc
      721 ctctccattg acctgaagat ccacgtggct cattggtaca atgtcagata ccgaggaaat
      781 gcttttccgg tagaaatcac ccgccgagat gaccttgttg aacgacctga ccctgtggtt
      841 ttggcatttg acattgagac gaccaaactg cccctcaagt ttcctgatgc tgagacagac
      901 cagattatga tgatttccta catgatcgat ggccagggct acctcatcac caacagggag
      961 attgtttcag aagatattga agattttgag ttcaccccca agccagaata tgaaggcccc
     1021 ttttgtgtct tcaatgaacc cgatgaggct catctgatcc aaaggtggtt tgaacacgtc
     1081 caggagacca aacccaccat catggtcacc tacaacgggg acttttttga ctggccattt
     1141 gtggaggccc gggcagcagt ccacggtctg agcatgcagc aggagatagg cttccagaag
     1201 gacagccagg gggagtacaa ggcgccccag tgcatccaca tggactgcct caggtgggtg
     1261 aagagggaca gttaccttcc tgtgggcagt cataatctca aggcggccgc caaggccaag
     1321 ctaggctatg atcccgtgga gctagacccg gaggacatgt gccggatggc cacggagcag
     1381 ccccagactc tggccacgta ttctgtgtca gatgctgtcg ccacttacta cctgtacatg
     1441 aagtacgtcc acccattcat ctttgctctg tgcaccatta ttcccatgga gcccgacgag
     1501 gtgctgcgga agggctctgg cactctgtgt gaggccttgc tgatggtgca ggccttccac
     1561 gccaacatca tcttccccaa caagcaagag caggagttca ataagctgac ggacgacgga
     1621 cacgtgctgg actctgagac ctacgtcggg ggccacgtgg aggccctcga gtctggggtt
     1681 ttccgcagcg atatcccttg ccggtttagg atgaatcctg ccgcctttga cttcctgctg
     1741 cagcgggttg agaagacctt gcgccacgcc cttgaggaag aggagaaagt gcctgtggag
     1801 caagtcacca actttgaaga ggtgtgtgat gagattaaga gcaagcttgc ctccctgaag
     1861 gacgttccca gccgcatcga gtgtccactc atctaccacc tggacgtggg ggccatgtac
     1921 cccaacatca tcctgaccaa ccgcctgcag ccctctgcca tggtggacga agccacctgt
     1981 gctgcctgtg acttcaataa gcctggagca aactgccagc ggaagatggc ctggcagtgg
     2041 aggggcgagt tcatgccagc cagtcgcagc gaataccatc ggatccagca ccagctggag
     2101 tcagagaagt tccccccctt gttcccagag gggccagctc gggcctttca tgaactgtcc
     2161 cgcgaggaac aggcgaaata cgagaagaga aggctggcgg attactgccg gaaagcctac
     2221 aagaagatcc acatcaccaa ggtggaagag cgtctcacca ccatctgcca gcgggaaaac
     2281 tccttctacg tggacaccgt gcgtgccttc cgggacaggc gttacgagtt caaagggctc
     2341 cacaaggtgt ggaaaaagaa gctctcggcg gccgtggagg tgggcgacgc ggctgaggtg
     2401 aagcgctgca agaacatgga ggtgctgtat gactcgctgc agctggccca caagtgcatc
     2461 ctgaactcct tctatggcta tgtcatgcgc aagggggctc gctggtactc catggagatg
     2521 gctggcatcg tctgcttcac aggggccaac atcatcaccc aggcacggga gctgatcgag
     2581 cagattggga ggcccttaga gctggacaca gatggtatat ggtgcgtcct gcccaacagc
     2641 ttcccagaaa attttgtctt caagacgacc aatgtgaaga agcccaaagt gaccatctcc
     2701 tacccaggcg ccatgttgaa catcatggtc aaggaaggct tcaccaatga ccagtaccag
     2761 gagctggctg agccgtcctc actcacctac gtcacccgct cagagaacag catctttttt
     2821 gaggttgatg ggccctacct tgccatgatt cttccagcct ccaaggaaga aggcaagaaa
     2881 ttgaagaaga ggtatgctgt gttcaatgaa gacggttctc tggctgagct caagggcttt
     2941 gaggtcaaac gccgcgggga actgcagctg attaagatct tccaatcctc ggtgtttgag
     3001 gccttcctca agggcagcac gctggaagag gtgtatggct ctgtagccaa ggtggctgac
     3061 tactggctgg acgtgctgta cagcaaggca gccaacatgc ctgactctga gctattcgag
     3121 ctcatctctg agaaccgttc catgtctcgg aagctggaag attacgggga gcagaagtct
     3181 acgtccatca gcacagcaaa gcgcctggcc gagttcctgg gagaccagat ggtcaaggat
     3241 gcagggctga gttgccgcta catcatctcc cgcaagcccg agggctcccc tgtcacggag
     3301 agggccatcc cacttgccat tttccaagca gagcccacgg tgaggaagca ctttctccgg
     3361 aaatggctca agagctcttc ccttcaagac tttgatattc gagcaattct ggattgggac
     3421 tactacattg agcggctggg aagcgccatc cagaagatca tcaccatccc tgcggccctg
     3481 cagcaggtaa agaacccagt gccacgtgtc aaacaccccg actggctgca caaaaaactg
     3541 ctggagaaga atgatgtcta caagcagaag aagatcagtg agctcttcac cctggagggc
     3601 aggagacagg tcacgatggc cgaggcctca gaagacagtc cgaggccaag tgctcctgac
     3661 atggaggact tcggcctcgt aaagctgcct cacccagcag cccctgtcac tgtgaagagg
     3721 aagcgagttc tttgggagag ccaggaggag tcccaggacc tcacgccgac tgtgccctgg
     3781 caggaaatct tggggcagcc tcccgccctg ggaaccagcc aggaggaatg gcttgtctgg
     3841 ctccggttcc acaagaagaa gtggcagctg caggcccggc agcgcctcgc ccgcaggaag
     3901 aggcagcgtc tggagtcggc agagggtgtg ctcaggcccg gggccatccg ggatggtcct
     3961 gccacggggc tggggagctt cttgcgaaga actgcccgca gcatcctgga ccttccgtgg
     4021 cagattgtgc agatcagcga gaccagccag gccggcctgt tcaggctgtg ggcgctcgtt
     4081 ggcagtgact tgcactgcat caggctgagc atcccccgtg tgttctacgt gaaccagcga
     4141 gtcgctaaag cggaggaggg tgcttcgtat cgcaaggtaa atcgggtcct tcctcgctcc
     4201 aacatggtct acaatctcta tgagtattca gtgccagagg acatgtacca ggaacacatc
     4261 aacgagatca acgctgagct gtcagcgcca gacatcgagg gcgtatatga gactcaggtt
     4321 ccgttactgt tccgggccct ggtgcacctg ggctgtgtgt gtgtggtcaa taaacagctg
     4381 gtgaggcacc tttcaggctg ggaagcagag acctttgctc ttgagcacct ggagatgcgc
     4441 tctctggccc agttcagcta cctggaacca gggagtatcc gccatatcta cctgtaccac
     4501 cacgcacagg cccacaaagc gctcttcggg atcttcatcc cctcacagcg cagggcatcc
     4561 gtctttgtgc tggacactgt gcgcagcaac cagatgccca gccttggcgc cctgtactca
     4621 gcagagcacg gcctcctcct ggagaaggtg ggccctgagc tcctgccacc ccccaaacac
     4681 accttcgaag ttcgggcaga aactgacctg aagaccatct gcagagccat ccagcgattc
     4741 ctgctcgcct acaaggagga gcgccggggg cccacactca tcgctgttca gtccagctgg
     4801 gagctgaaga ggctggccag tgaaattcct gtcttggagg aattcccact ggtgcctatc
     4861 tgtgtggctg acaagatcaa ctatggggtc ctggactggc agcgccatgg agcccggcgc
     4921 atgatccgtc actacctcaa cctggacacc tgcctgtcgc aggccttcga gatgagcagg
     4981 tactttcaca ttcccattgg gaacctacca gaggacatct ccacattcgg ctccgacctc
     5041 ttctttgccc gccacctcca gcgccacaac cacctgctct ggctgtcccc tacagcccgc
     5101 cctgacctgg gtggaaagga ggctgatgac aactgtcttg tcatggagtt cgatgaccaa
     5161 gccactgttg agatcaacag ttcaggctgt tactccacag tgtgtgtgga gctggacctt
     5221 cagaacctgg ccgtcaacac cattctccag tctcaccatg tcaacgacat ggagggggcc
     5281 gacagcatgg ggatcagctt cgacgtgatc cagcaggcct ccctggagga catgatcacg
     5341 ggtggtcagg ctgccagtgc cccggccagc tacgatgaga cagccctgtg ctctaacacc
     5401 ttcaggatcc tgaagagcat ggtcgtgggc tgggtgaagg agatcaccca gtaccacaac
     5461 atctatgcag acaaccaggt gatgcacttc taccgctggc ttcggtcgcc atcctctctg
     5521 cttcatgacc ctgccctgca ccgcacactc cacaacatga tgaagaagct cttcctgcag
     5581 ctcatcgctg agttcaagcg cctggggtca tcagtcatct acgccaactt caaccgcatc
     5641 atcctctgta caaagaagcg ccgtgtggaa gatgccatcg cttacgtgga gtacatcacc
     5701 agcagcatcc attcaaagga gaccttccat tctctgacaa tttctttctc tcgatgctgg
     5761 gaatttcttc tctggatgga tccatctaac tatggcggaa tcaaaggaaa agtttcatct
     5821 cgtattcact gtggactgca agactcccag aaagcagggg gagcagagga tgagcaggaa
     5881 aatgaggacg atgaggagga aagagatggg gaggaggagg aagaggcgga ggaatccaac
     5941 gtggaggatt tactggaaaa caactggaac attttgcagt ttttgccaca ggcagcctcc
     6001 tgccagaact acttcctcat gattgtttca gcgtacatcg tggccgtgta ccactgcatg
     6061 aaggacgggc tgaggcgcag tgctccaggg agcacccccg tgaggaggag gggggccagc
     6121 cagctctccc aggaggccga gggggcggtc ggagcccttc ccggaatgat caccttctct
     6181 caggattatg tcgcaaatga gctcactcag agcttcttca ccatcactca gaagattcag
     6241 aagaaagtca caggctctcg gaactccact gagctctcag agatgtttcc tgtcctcccc
     6301 ggttcccact tgctgctcaa taaccctgcc ctggagttca tcaaatacgt gtgcaaggtg
     6361 ctgtccctgg acaccaacat cacaaaccag gtgaataagc tgaaccgaga cctgcttcgc
     6421 ctggtggatg tcggcgagtt ctccgaggag gcccagttcc gagacccctg ccgctcctac
     6481 gtgcttcctg aggtcatctg ccgcagctgt aacttctgcc gcgacctgga cctgtgtaaa
     6541 gactcttcct tctcagagga tggggcggtc ctgcctcagt ggctctgctc caactgtcag
     6601 gcgccctacg actcctctgc catcgagatg acgctggtgg aagttctaca gaagaagctg
     6661 atggccttca ccctgcagga cctggtctgc ctgaagtgcc gcggggtgaa ggagaccagc
     6721 atgcctgtgt actgcagctg cgcgggagac ttcgccctca ccatccacac ccaggtcttc
     6781 atggaacaga tcggaatatt ccggaacatt gcccagcact acggcatgtc gtacctcctg
     6841 gagaccctgg agtggctgct gcagaagaac ccacagctgg gccattagcc agccccgggc
     6901 cccgggtgcc tctgcgtccg tgccaggcct cctgatgcca aggccacatc cccgtgcttc
     6961 cagtgaccag accactgacc accctgactg tccaaacctg tgaccccagg ccagggaacg
     7021 gggaggaaac caaagaaaac cattttcagg gagctcagac gtcacaggag ggagcgggag
     7081 caggatgtgg ccctggcctc gccagagcac ctgaagaagc aggccgtgag cgaggctgcg
     7141 agtgccctgg gcgccgtttc tcacgcagtg aatgcttttc caggcctctg ttgcttcctg
     7201 caccacacct ggtggggtgg gagcgtcctc taggtgcccc tagttctttg tcctgcctcc
     7261 cagagggagg aaaagcccct gggggcttct ggctccctga gattgggctc tgagacgaga
     7321 cgggttccca aggccctggt ggggctggag tctcacctgt ttgcatggag aaatgggctg
     7381 gccccacagc ctcacaggag cagtttgtgg gctggtttcc ccaggaatcc agaccctaac
     7441 ccgtgagaat ctggattttg gcttgtgagc cctgcttatt tggagccggg tctagaggga
     7501 accctctatc agcctcagga aaacaagacc tctgtgcacc tcacttttgg ctcactgcag
     7561 cccttgtcct tcacctccac acaggaccag ctggaagcag aaagaagaaa ggccaatttc
     7621 acagggcacc aaacaagtat gaaatgtaaa tcagaaatgc agacacccca gacgagagcc
     7681 tcacaggagg gagggggccc cacaggctcc ccaggaggct cgtgtctttg gcccagagcc
     7741 agccttagtt tgtccctgcc atctactgtc tgaggccatc gctgctacac tttgttttta
     7801 tttgtatttc atactgaagt ttc
//
