LOCUS       NM_003937              15151 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens kynureninase (KYNU), transcript variant 1, mRNA.
ACCESSION   NM_003937
VERSION     NM_003937.3
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 15151)
  AUTHORS   Thiem,C.E., Stegmann,J.D., Hilger,A.C., Waffenschmidt,L.,
            Bendixen,C., Kollges,R., Schmiedeke,E., Schafer,F.M., Lacher,M.,
            Kosch,F., Grasshoff-Derr,S., Kabs,C., Neser,J., Jenetzky,E.,
            Fazaal,J., Schumacher,J., Hoefele,J., Ludwig,K.U. and Reutter,H.
  TITLE     Re-sequencing of candidate genes FOXF1, HSPA6, HAAO, and KYNU in
            522 individuals with VATER/VACTERL, VACTER/VACTERL-like
            association, and isolated anorectal malformation
  JOURNAL   Birth Defects Res 114 (10), 478-486 (2022)
   PUBMED   35362267
  REMARK    GeneRIF: Re-sequencing of candidate genes FOXF1, HSPA6, HAAO, and
            KYNU in 522 individuals with VATER/VACTERL, VACTER/VACTERL-like
            association, and isolated anorectal malformation.
REFERENCE   2  (bases 1 to 15151)
  AUTHORS   Morozov,V., Lagaye,S. and Morozov,A.
  TITLE     The TZM-bl Reporter Cell Line Expresses Kynureninase That Can
            Neutralize 2F5-like Antibodies in the HIV-1 Neutralization Assay
  JOURNAL   Int J Mol Sci 23 (2), 641 (2022)
   PUBMED   35054825
  REMARK    GeneRIF: The TZM-bl Reporter Cell Line Expresses Kynureninase That
            Can Neutralize 2F5-like Antibodies in the HIV-1 Neutralization
            Assay.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 15151)
  AUTHORS   Zhao,L., Wang,B., Yang,C., Lin,Y., Zhang,Z., Wang,S., Ye,Y. and
            Shen,Z.
  TITLE     TDO2 knockdown inhibits colorectal cancer progression via
            TDO2-KYNU-AhR pathway
  JOURNAL   Gene 792, 145736 (2021)
   PUBMED   34051337
  REMARK    GeneRIF: TDO2 knockdown inhibits colorectal cancer progression via
            TDO2-KYNU-AhR pathway.
REFERENCE   4  (bases 1 to 15151)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   5  (bases 1 to 15151)
  AUTHORS   Liu,Y., Feng,X., Lai,J., Yi,W., Yang,J., Du,T., Long,X., Zhang,Y.
            and Xiao,Y.
  TITLE     A novel role of kynureninase in the growth control of breast cancer
            cells and its relationships with breast cancer
  JOURNAL   J Cell Mol Med 23 (10), 6700-6707 (2019)
   PUBMED   31332944
  REMARK    GeneRIF: A novel role of kynureninase in the growth control of
            breast cancer cells and its relationships with breast cancer.
REFERENCE   6  (bases 1 to 15151)
  AUTHORS   Toma,S., Nakamura,M., Tone,S., Okuno,E., Kido,R., Breton,J.,
            Avanzi,N., Cozzi,L., Speciale,C., Mostardini,M., Gatti,S. and
            Benatti,L.
  TITLE     Cloning and recombinant expression of rat and human kynureninase
  JOURNAL   FEBS Lett 408 (1), 5-10 (1997)
   PUBMED   9180257
REFERENCE   7  (bases 1 to 15151)
  AUTHORS   Alberati-Giani,D., Buchli,R., Malherbe,P., Broger,C., Lang,G.,
            Kohler,C., Lahm,H.W. and Cesura,A.M.
  TITLE     Isolation and expression of a cDNA clone encoding human
            kynureninase
  JOURNAL   Eur J Biochem 239 (2), 460-468 (1996)
   PUBMED   8706755
REFERENCE   8  (bases 1 to 15151)
  AUTHORS   Mark,P. and Dunwoodie,S.
  TITLE     Congenital NAD Deficiency Disorder
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   37499065
REFERENCE   9  (bases 1 to 15151)
  AUTHORS   Ubbink,J.B., Vermaak,W.J. and Bissbort,S.H.
  TITLE     High-performance liquid chromatographic assay of human lymphocyte
            kynureninase activity levels
  JOURNAL   J Chromatogr 566 (2), 369-375 (1991)
   PUBMED   1939450
REFERENCE   10 (bases 1 to 15151)
  AUTHORS   Inada,J., Okuno,E., Kimura,M. and Kido,R.
  TITLE     Intracellular localization and characterization of
            3-hydroxykynureninase in human liver
  JOURNAL   Int J Biochem 16 (6), 623-628 (1984)
   PUBMED   6468727
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL548658.3, U57721.1,
            AW296221.1 and AC013437.8.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_003937.2.
            
            Summary: Kynureninase is a pyridoxal-5'-phosphate (pyridoxal-P)
            dependent enzyme that catalyzes the cleavage of L-kynurenine and
            L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic
            acids, respectively. Kynureninase is involved in the biosynthesis
            of NAD cofactors from tryptophan through the kynurenine pathway.
            Alternative splicing results in multiple transcript variants.
            [provided by RefSeq, Nov 2010].
            
            Transcript Variant: This variant (1) differs in the 5'UTR compared
            to variant 3.
            
            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 :: SRR5189661.72400.1,
                                           SRR1163657.300687.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000264170.9/ ENSP00000264170.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-710               AL548658.3         167-876
            711-1623            U57721.1           725-1637
            1624-1634           AW296221.1         17-27               c
            1635-15151          AC013437.8         16719-30235
FEATURES             Location/Qualifiers
     source          1..15151
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q22.2"
     gene            1..15151
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /note="kynureninase"
                     /db_xref="GeneID:8942"
                     /db_xref="HGNC:HGNC:6469"
                     /db_xref="MIM:605197"
     exon            1..73
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            74..261
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     CDS             93..1490
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /EC_number="3.7.1.3"
                     /note="isoform a is encoded by transcript variant 1"
                     /codon_start=1
                     /product="kynureninase isoform a"
                     /protein_id="NP_003928.1"
                     /db_xref="CCDS:CCDS2183.1"
                     /db_xref="GeneID:8942"
                     /db_xref="HGNC:HGNC:6469"
                     /db_xref="MIM:605197"
                     /translation="MEPSSLELPADTVQRIAAELKCHPTDERVALHLDEEDKLRHFRE
                     CFYIPKIQDLPPVDLSLVNKDENAIYFLGNSLGLQPKMVKTYLEEELDKWAKIAAYGH
                     EVGKRPWITGDESIVGLMKDIVGANEKEIALMNALTVNLHLLMLSFFKPTPKRYKILL
                     EAKAFPSDHYAIESQLQLHGLNIEESMRMIKPREGEETLRIEDILEVIEKEGDSIAVI
                     LFSGVHFYTGQHFNIPAITKAGQAKGCYVGFDLAHAVGNVELYLHDWGVDFACWCSYK
                     YLNAGAGGIAGAFIHEKHAHTIKPALVGWFGHELSTRFKMDNKLQLIPGVCGFRISNP
                     PILLVCSLHASLEIFKQATMKALRKKSVLLTGYLEYLIKHNYGKDKAATKKPVVNIIT
                     PSHVEERGCQLTITFSVPNKDVFQELEKRGVVCDKRNPNGIRVAPVPLYNSFHDVYKF
                     TNLLTSILDSAETKN"
     exon            262..382
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            383..465
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            466..527
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            528..599
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            600..674
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            675..821
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            822..920
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            921..994
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            995..1047
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1048..1133
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1134..1364
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1365..15151
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1612..1617
                     /regulatory_class="polyA_signal_sequence"
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /note="hexamer: AATATA"
     polyA_site      1629
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /note="major polyA site"
     regulatory      2277..2282
                     /regulatory_class="polyA_signal_sequence"
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /note="hexamer: AATAAA"
     polyA_site      2296
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
     regulatory      10030..10035
                     /regulatory_class="polyA_signal_sequence"
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /note="hexamer: AATAAA"
     polyA_site      10061
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
     regulatory      15131..15136
                     /regulatory_class="polyA_signal_sequence"
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
                     /note="hexamer: AATAAA"
     polyA_site      15151
                     /gene="KYNU"
                     /gene_synonym="KYNUU; VCRL2"
ORIGIN      
        1 acattttcaa ggaattcttg agaggttctt ggagagattc tgggagccaa acactccatt
       61 gggatcctag ctgttttaga gaacaacttg taatggagcc ttcatctctt gagctgccgg
      121 ctgacacagt gcagcgcatt gcggctgaac tcaaatgcca cccaacggat gagagggtgg
      181 ctctccacct agatgaggaa gataagctga ggcacttcag ggagtgcttt tatattccca
      241 aaatacagga tctgcctcca gttgatttat cattagtgaa taaagatgaa aatgccatct
      301 atttcttggg aaattctctt ggccttcaac caaaaatggt taaaacatat cttgaagaag
      361 aactagataa gtgggccaaa atagcagcct atggtcatga agtggggaag cgtccttgga
      421 ttacaggaga tgagagtatt gtaggcctta tgaaggacat tgtaggagcc aatgagaaag
      481 aaatagccct aatgaatgct ttgactgtaa atttacatct tctaatgtta tcatttttta
      541 agcctacgcc aaaacgatat aaaattcttc tagaagccaa agccttccct tctgatcatt
      601 atgctattga gtcacaacta caacttcacg gacttaacat tgaagaaagt atgcggatga
      661 taaagccaag agagggggaa gaaaccttaa gaatagagga tatccttgaa gtaattgaga
      721 aggaaggaga ctcaattgca gtgatcctgt tcagtggggt gcatttttac actggacagc
      781 actttaatat tcctgccatc acaaaagctg gacaagcgaa gggttgttat gttggctttg
      841 atctagcaca tgcagttgga aatgttgaac tctacttaca tgactgggga gttgattttg
      901 cctgctggtg ttcctacaag tatttaaatg caggagcagg aggaattgct ggtgccttca
      961 ttcatgaaaa gcatgcccat acgattaaac ctgcattagt gggatggttt ggccatgaac
     1021 tcagcaccag atttaagatg gataacaaac tgcagttaat ccctggggtc tgtggattcc
     1081 gaatttcaaa tcctcccatt ttgttggtct gttccttgca tgctagttta gagatcttta
     1141 agcaagcgac aatgaaggca ttgcggaaaa aatctgtttt gctaactggc tatctggaat
     1201 acctgatcaa gcataactat ggcaaagata aagcagcaac caagaaacca gttgtgaaca
     1261 taattactcc gtctcatgta gaggagcggg ggtgccagct aacaataaca ttttctgttc
     1321 caaacaaaga tgttttccaa gaactagaaa aaagaggagt ggtttgtgac aagcggaatc
     1381 caaatggcat tcgagtggct ccagttcctc tctataattc tttccatgat gtttataaat
     1441 ttaccaatct gctcacttct atacttgact ctgcagaaac aaaaaattag cagtgttttc
     1501 tagaacaact taagcaaatt atactgaaag ctgctgtggt tatttcagta ttattcgatt
     1561 tttaattatt gaaagtatgt caccattgac cacatgtaac taacaataaa taatatacct
     1621 tacagaaaat ctgatataat ttttcagagt ctgtggcact aaggagtcca cagggctgcc
     1681 taggtgcttt gtgtttgggg gaccaaaact gtgttggttc aagtattatc tatacagtct
     1741 ctataagctg tcacatttca tggtcattga aatgttttat gttggtttaa tttctgattt
     1801 aactgacaac ttcataatgt atgtgcaatt attgtgtcaa atttagaaat attactttag
     1861 cttcaattta ccaaggagtt tctttgaagc attgtagtct gatatatata tatatatata
     1921 tatatatata tatatatata tatatatatg tgtgtgtgtg tgtgtgtata tatatatata
     1981 tatatcatat atatatgata gtggctttca aatttttttg ggtacaatcc acattgctcc
     2041 tgctgatctg taatatcaga aaccagtatt tatgtgaata tatgagaaat attattgatt
     2101 ctaagatatt ttatcatatt ttaacatctt tgaaagagga cccatctttc aattttcgat
     2161 caatagtttc ttacagtcac cattggccat ctttctcgtt accatctatg aaattagcat
     2221 gcatctcaaa taaacagtta ccatcttcta tttgataaaa tagtctaaat agcaaaaata
     2281 aaagttttta caattatttg cctgtgctct aataggtact attctatttt atctcataag
     2341 aaatgttgga aactcattat attgatttcc ttacccactc atgggcccta attcacactt
     2401 tttaagaatg tttctttctt taatgttatc ataatctctt actttttaaa tgagaacttc
     2461 ccctaatata agagcttaga tattatatta ctatgtttcc atagtaaata aataacccca
     2521 agatcttttt ggggattaga gatataagaa atatgtgctc catctcttga catctttatc
     2581 tcaaatctat ggacctttct tacccactgt gaaaaaccta aagttacact tagccctgtt
     2641 ggacttacct agttttcaat tgttgatgcc acaatcatta tttataagtt gacaaaatag
     2701 tgtagatttg tatacatagt caacaaaaag agtgacataa ttattgcctc caattaaaca
     2761 agtttgaatg aaataaacaa acttagataa acacttcgga tggtagacgt aaacaataat
     2821 atgtggaact ccaacatcaa cacctaccaa taccagtaac tactgatatt tatcatgtac
     2881 ttaccatgta ccatgtattg tgctacatta ctcatgttat ctcccttaat tgagtggcta
     2941 catactgctt tagcaaatct tcctactgta actaatcctc atagatggaa gagttctcaa
     3001 aaccttaaaa ctcatgcata agtggattca tatacatata taaaaatata tataaatata
     3061 tatactttat atatatttat atttatatat ttatatattt atattttaat atatttatat
     3121 aaatatatat aaagtataat atatataaag tataaatata tatatattta tactttaagt
     3181 tcttggatac acgtgcagaa catgcaggtt tgttacatag gtatacatgt gccgtggtgg
     3241 attgctgcac ccatcaaccc gtcatctaca tcaggtattt ctcctaatgc tcaccctcct
     3301 cttatcccca actacccaaa aggacctggt gtgtgatgtt cccctccctg tgttcatatg
     3361 ttctcattgt tcaactctca cttatgggta agaacatgca gtgtttgatt ttctgttcct
     3421 ctgttagttt gctgagaatg atggtttcca gcttcatcca tgtccctgca aaggacatga
     3481 actcattctt ttttatggct gcatagtatt ccatggtata tatgtgccac attttcttta
     3541 tccagtctat cattgatggc catttgagtt ggttccaagt cttcgctatt gtgaatagtg
     3601 ctgcaatgaa catatgtgtg catgtgtctt tatagtagaa tgatttataa tccttagggt
     3661 atacccagta atgggattgc tgggttaaat ggtatttctg gttctagatc ctcgaggaat
     3721 tgccacactg tcttccacaa tggttgaact aatttatact cccaccaaca gtgtaaaagc
     3781 attcctattt ctccacatcc tctcagcatc tgttgtttct tgacttttta atgattagca
     3841 ttctaactgg cgtgagatgg tatttcattg tggttttgat ttgcatttct ctaatgacca
     3901 gtgatgatga gttttttttc atatatttgt tggccgcata aatgtcttct tttgagaagt
     3961 gtctgttcgt atccttcacc cactttttga tggggttgtg tttttcttgt aaatttattt
     4021 aagtcccttg tagattctgg atattttccc tttgtcagat ggatagattg caaaaatttt
     4081 ctcccgttct gtaggttgcc cgatcactct gatgatagtt tcttttgctg tgtagaagct
     4141 ctttagttta atcaggttcc atttgtcagt tttggctttt gttgcaattg cttttggtgt
     4201 tttagtctta aattctttgc ccatgcctat gtcctgaatg gtattgccta gatattcttc
     4261 tagggttttt tttttggctt taggtcttgc agttaagtct ttaatctatc ttgagttaat
     4321 ttttgtataa gatataagaa aggggtccag tttcagtttt ctgcatatgg ctagccagtt
     4381 ttcccaacac tatttattaa atagggaatc ttttccccat tgcttgtttt tgtcaggttt
     4441 atcaaagatc agatggttgt aaatgtgtgg tgttatttct gaggcctctg ttttgttcca
     4501 ttggtctata tgtctgtttt tgttcagtac catgctgttt tgtttactat agccttgtag
     4561 tatagtttga agtcaggtag tgtgatgcct ccagctttgt tctttttgct taggattgtc
     4621 ttggcaatac aggttctttt ttggttccat atgaaattta aagtagtttt ttctaattct
     4681 gtgaagaaag acaatggtag cttgatggaa atagcattga atctataaat tactctcagc
     4741 aatatggcca ttttcaggat attgattctt cctatctatg agcatggaat gtttttccat
     4801 ttgtttgtgt cctctctggt atccttgagc agtggtttgt agttctcatt gaagtagtcc
     4861 ttcacatccc ttgtaagttg tattcctagg tattttattc tctttgcagc aattgtgaat
     4921 gggagttcac tcatgatttg gttctctgtt tgtcctatat acatatgttg gtatatagga
     4981 atgcttttat tttaaagatg gaagatgatg tctctctatg taactcaggc aggtctcaaa
     5041 ctcctgggct caaatgatcc tcctacctta acctcctgag tagctgagac tttagtcaca
     5101 caccaccatg cctgaccagg aattgttttt caacttcata gtggtaaaca aaacatatgt
     5161 gttttcagtt ctcatggaac aagcagctta gtaggagaaa catatgttga acttgtaagc
     5221 agagaagtaa atctataatg acaaatcata atttctgaag ggtattaatt agatgtttga
     5281 gtgaggggaa atattggaag gtgctcataa gtttataaat gttctaaaat atttcatgct
     5341 aatcacatta aaattatatc aaagtatata aacatatcat ggaaaacata atcagcacca
     5401 tgtactcaac acctaggtta aaaaatagca ttaaaaattc tctttccagc tcacattctg
     5461 ctccctcccc aaatccacag ataaccatcg aattatattt tgttttcttc attcccttac
     5521 tttctttaag ttttacaccc atgtatgtac ccataaaaat ctattagcta attttggttg
     5581 tgcatgaata ttgtatcaat gcaattatac tgtatatatt ctgcttttgc acatattttt
     5641 agattcatcc atttgtggca tgtagctttc cattcatttt cactgctgct cagtattgta
     5701 ttacaaattt tacatttgtt ttagggaaga gtcataaacc atctttaagt tctcctatgt
     5761 tacaagtaat tttgtaaatg atgtgaggtg gtgattctat ttcatttttt cccatataga
     5821 taatttatat tattaataat tccttctatt tcataagcca ggtttctata tatctatata
     5881 aatatagata tgtagatata tgaaagcaat atatatatgg atgtctttct gggctatctg
     5941 tactttcaca ctggctaatt tgcttgtttt ttcatcaata cttcacttcc ttaattacta
     6001 caacatagca gggcctggca tctgctagat taaatctctc agcttctttt tattaagatt
     6061 gccctgaatt gtcctggtta tcctgggccc cctacttttt ttatattttt gaatacatct
     6121 aaataaattt agaataaatc tattgtgttc cataaaaccc ctgttgggat ttcaattgaa
     6181 ctgcaattaa attttagatc agttttggaa gaattgactc aatagtgagc cttcctaccc
     6241 aagaccatgg catttatttt catttattta tgatttcttt aatgcttctc aaaatttttt
     6301 attttctcta ttatggaaac gcacatttat agtttgacaa attcctaagt acttctaatt
     6361 ttattgtcat tccacattat cttttttgtt gttgttttaa aagacagggt ctccctctgt
     6421 cacccaggct ggagtgtact gatgtgatta tagctcactg cagtctcaac ctcctgggct
     6481 caagtgatcc tcccacgtca gcctgtggag tagctaggac tacaggcatg tgccacaatg
     6541 cctggctcat ttttaagtgt taagttaaaa aaagttgtag aaacagtgtt ttgctacatt
     6601 tcccaggctg gtctcaaact cctggcccca agcaatcttc ctgcctcagc ttcccatatt
     6661 cggattatac gcatgaggca ttgcaccagc cccatgtgtt atcttttata aaatttaaca
     6721 tttaactgat aattgatact gtatatacat gaattcaatt ggtatctatt tttaatatgg
     6781 gaaattttat gcaaatgagc acatttttct cccttccttc cttccttctt tccttgttct
     6841 ctttctttct ctctctttct ctttctctct ttctttcttt ctttctttct cacagggtgt
     6901 cactctgttg cccaggcgga gtgcagtggc acatgatcat agctcactgc aacctccaac
     6961 tcaaacactt gagtgatcct ctgtcccccg tttcccaagc agctgggact acaggcacat
     7021 gccacgatgc caagctaatt tttaaaaata attttttttg tagattcaga gtcttgctat
     7081 gttgcccagg ctaatctcaa actcctggcc tcaagcagtc ctccctcctc agcctcccat
     7141 tacaggcata agctgccact cctggacctc tttttttttt tttttttttt ttttttgagg
     7201 cagtctctct ctgtcaccca ggctggagta tagtggcacg atctcagctc actgcgggtt
     7261 caagcaattt tcatgcctca gcctcccaag tagctgggat tacaggcatg ggccactatg
     7321 cccagctaat ttttgtattt ttcatagaga caggatttca ccatgttggc taggctggta
     7381 tcaaactcct gacttcaggt gatccgccca ctttgacctt ccaaaatgct gggattacgt
     7441 gtgagccacc aaacccagcc cctcattttc tttttgattt ttatttattt tcctctgttt
     7501 ttcttctttt ggatttaggg atgtgtgtgt ggaggtgtat tgagtccgtt ttttctttct
     7561 atttgtgtgg aaattataca cttattcttt gttattttag caattactct ggctatttta
     7621 acatgcaaat ataatgaagt ttagaattag ccatttttta taactctcct tctgactagt
     7681 tgaagaaatg agaatgcttt aacatcaaac agccaactct ttacttatac actattgcta
     7741 ttcattatag catttttagt ctagcttcct ccctcctctt tctctctctc tctctctgtc
     7801 tctctctctc tcactaatgt ttgctatttc tccctacaat tcagaatttt atttatggat
     7861 gaagtacata tataatttat tacaattcat tttaatgaaa aacttttagt ggtaaattgt
     7921 attagtcttt gggaaaaaac atttattgat accattttct cattacttaa aaatagtttc
     7981 acttcatata gaattctatg tcgacagtaa ttttctttca ggaagtagaa aatattaagt
     8041 tacagtattt tggcttccat tactgctgtt aagcattcag atcatcagag aaatgcaaat
     8101 cagaaccaca atgagatgcc atctcatgcc agtcagaatg gcaatcatta aaaagtcagg
     8161 aaacaataga tgctggtgag gctgtggaga aataagaatg cttttacact gttagtggga
     8221 atgtaaatta gttcaaccat tgctcttaag ggctctttgt ctttaatgat ccgcattttt
     8281 attatgatgt gtctaggcag ttattattgt gtttattcta tttctttatt tgctgtctat
     8341 ccaagatttg aggattaatt ttttaatttc tagaaaattc agaagtatta tttatttatt
     8401 caattattac ctctttctat tatttccttt ttaaaataaa agggtatatg ttagaatttt
     8461 tcactctctc ctttatgcct ttaacttcat attttctatt tctttgaatt tctgggctgc
     8521 attcttaaga attctaaaac atatatttta gtttctaaaa gtttcattag atttctgttc
     8581 aaaattcctt ccatttgtga tctttcgaat gtgcttctgc tttaggcatt agtagtggac
     8641 attctggttc cccattgagc ttccctgcat cagctgtttt gcctggtggc tgccaccaac
     8701 gcttttagct acctccctcc tcaaactttg gggtcaggcc acacactata aaggattgga
     8761 aaaaaaaatg aaaatatgaa aaacttacac tttgtatcag tcaggagaag gataatcttc
     8821 acactacagt ttatgcttca gaagccaccc cttctctgtg gattagacca tgactagaag
     8881 tttcctgaga ccatcccttg cccagctctt ttggtgatcc ccttcacttc ctctgttaca
     8941 ggtttccctg atgagcactc cttcaataaa acatagtcat ccaaatccca atctcaagca
     9001 cggtgtcacg ggaacctgat ctaagtcagc attttcttta ttcttaatca caactagttg
     9061 atagtccata tctaatatat aatgaatgta cagttgtttc tgttggagtt cacatatgat
     9121 gccttgtttc ctttgtagtt ttgtgattga tagcttcgaa ctgctcattt accttgacct
     9181 tttgaattct ttgaaaactg agttaagtct gattttccag agtttttatg tttgcttctg
     9241 tcagttgcag agaatcaatg agaagaacac tttaaattct tgttttcggt ttttttccaa
     9301 tcacataagt aggatttacc tgaatatata tataatatat aaacatatat ttatataaaa
     9361 taaaaacata taaaatatga aatatataat acagtataaa atctatttta tgtaaaatct
     9421 attttatgta aacatgataa ttaaatatat atttaaataa tataaatata ataaatattt
     9481 gaagcaattg tattttttaa aaatttcttc taaagaaaac caggatacat gtgcagaacc
     9541 tgcaggtttg ttacataggt atacgtgtgc catggtggtt tgctgcacct attgacccgt
     9601 cctctaagtt ccctcccctc acctcccacc ccccagcagg ccctggtgtg tgttgttccc
     9661 ctctctgtgt ccatgtattc tcgcctccca cttatgagtg agaacacgcg atgtttggtt
     9721 ttctgttcct gtgttaattt gctgaggatg atagcttcca gcttcatcca cgtccctgca
     9781 aaggacatga tctcattcct caatactatg gctacgtagt attccatggt gtatatatac
     9841 cacattttct tcatccagtc atgcaaattt atatgaatgt caattctttt atagtgatct
     9901 tctggggcta ttacaatata tagggctgtt tttttaaaac taattatatt tatttcatgt
     9961 tgctttaact tattaaaaaa cagactgaag aaagactggg tgtgaagtca gtaaattaat
    10021 ttcaaattaa ataaactttt ctacagctat tttatgctca ataactttct acttattctt
    10081 gagttcaaaa ctatatgggt tcacatttaa attatatagt gtattttctc cataaactga
    10141 agttgttaga acattgattt ttttaagtaa atggattttt gcaccacttc aagaaagaaa
    10201 ccttcaaaca gcctggaaat atcacatcaa taaagcacaa cctgggaatc aaagtattag
    10261 ggtaccttgt tactgagatt atggatgtga tgcttctgtg ggccattagc atgtgcactg
    10321 tgtgtatgat atgctctatg ttctcttccc actaataatt ttatttttaa tttcagcaag
    10381 atttagtctc aaataacaca ataataatgg aggtcattgt gaagtagtgg atgtaaatag
    10441 atctgatgtg gttttggttt attgcagtaa ttgttttgac taattctcta gtttttcaac
    10501 ttttgattgt ttaagatggt tcttgagtcc ttttgacatg accctatcta tttttgataa
    10561 cttcatagcc tttagtataa aaacaggtag gcttatatta catatttcca acttcaaact
    10621 tgttatttat ttatctaaga ctatacagtt cttttcagag aaaaaccttc tttataaacc
    10681 agaatcttaa caggaagagt gctcatttta attgagctga tcatgtttct aggatttttt
    10741 agttaaaaga aaatacatat tttaaaaata taaattatat ttttatttca tagtggtatt
    10801 ttcaattttg tctgggataa taagatgttt tatttaactt gtttgatttt gtagttttat
    10861 ctttgtggga aggacctggt aagaggtaat tgaatcatgg gggcaggact ttcccatgat
    10921 gttctcatga taatgaataa gtttcatgag atctgttggt ttcataatgt ggagtttccc
    10981 tgcaaaggct cttgtcctgt ctgtgccatt tgagacatgc ctttcaactt ctgccctgat
    11041 tgtgaggcct cccccgccat gtggaattgg gtcttacttt tgtaaattgc ccagtctcag
    11101 gtatgtcttt atcagcagcc tgaaaactga ctaatatagt aagttggcac cagtagagag
    11161 gggcactgct gaaaaggtac ccgaatatgt ggaagcaact ttaaactggg taacaggcag
    11221 aggttggaat ggtttggagg gctcataaga agacaggaaa gtgtgggaaa tttggaactc
    11281 cctagagact tgttgaatgg ctttaaccaa aatgctgata ataatatgaa caatgaagtc
    11341 caggctgagg tggtctcaga caaagataag gaacttcttg ggaactggag caaaggtgac
    11401 tcttgttatg ttttagacat aaagcaaaga gactggaggc attttgcccc tgccctagag
    11461 atttgtggga cattaaactt gagacagatt atttagggta tctggaggaa gaaattttta
    11521 tgcagcaaag cattcaagag gtgacttggt tgctattaaa ggcattcagt tttaaaaggg
    11581 aaatacagca taaaagttca gaaaattttc agcctgacaa tgcagtagaa aaggaaaacc
    11641 aattttctga ggagaaattt aagctggctg cagacattta cataagtaac aagaagctga
    11701 atgttaatca ctaagacaat gaggaaaatg tctccagggc atgtcagaga cctttgtggc
    11761 agcccctccc atcacagacc aggagcttta gaaggaaaaa tggcttcgtg ggctggtcac
    11821 agggtccctc tgctgtgtgc agtctaggga cttggtgccc tgtgtcccag cagctccatc
    11881 catgactaaa aggggccaag gtacagcttg ggctgtggct tcagagggtg gaagccccaa
    11941 gtcttggcag cttccatatg gtgttgagcc tgggttcaca gaagtcaaga actgaggttt
    12001 gggaacttac accaagattt cagaggatgt atggaaatgc ctggatgccc aggcagaagt
    12061 ttgctgcagg ggcaaggccc tcatggagaa cctctgctag ggcagtgaag aagggaaaag
    12121 tatggtggga gcccccatac agagtcccta ctgaggcacc acctagtgga gctttgagaa
    12181 gagggccact gtcctccaga actcaggatg gtaaatccac cacgcacctg gaaaagctgc
    12241 agacaattcc agcctgttaa agcagccagg agggggctat accctgcaaa gccacagggg
    12301 cggacctgct caaggctgtg ggagaccacc tcttgcatca gtgtgacctg gatgtgagac
    12361 atggagtcaa aggagatcat tttggagctt taagatttga ctgccccact ggatttcaga
    12421 ctttcatggg gcctgtagcc ccttcgtttt ggccaatgcc tcccatttgg agtggctgta
    12481 tttacccaat gcctgtatcc ccattgtatc taggaagtaa ctaacttgct tttgatttta
    12541 caggcccata ggtggaaggg cgatgtttct ttctggaggc tccagggaga actctgtttt
    12601 cttacctttt ctggattcta gaggcttccc acaatccttg gcttaaggtc catctttaag
    12661 ctttgtctct gatgagactt tggactgcgg acttttgagt taatgctgaa atgagttaag
    12721 actttgggtg actgttgcga agacatgatt ggttttgaaa tgtgagaaca tttaagaggg
    12781 gccaggggca gaatgatatg gtttgacttt gtccgcagtc aaatctcatc ttgaatttct
    12841 atgtgtttgg agaggtaccc ggtgggaggt aattgaatca tgagggcagg tcttttctgt
    12901 gctgttctca tgatggtgag taagtctcat gagatctgat ggttttataa aggggagttt
    12961 ccctgcccaa gttcttctct tgtctgccat catgtgcgat gtgcctttca cctctgccat
    13021 gattatgagg cctccctggc catgtggaac tgtgagtcca ttaaacctct ttcttttgta
    13081 aattgcccaa tcttgggaat gtctttatca gcagtgggaa aacggattaa tatactaatt
    13141 tatagctagt aggtaaaaag ccagggactt gccattagcg ttggaagtgg ggttgtgggg
    13201 gcagtcttgt ggaactgagc ccttaacctg tggggttgaa tgatatctcc aggtatatca
    13261 tgtcagaatt gaattcaatt agaggatacc tagcttgcgt tcaatgcaga attgcttgct
    13321 ggtgaggaga aatccctata cacattttgg tgaccagagg taaagcattt tatgttgatt
    13381 cttgagtgag agagtagaaa taacactggt tttttcccta tgtccttaca accaccaatt
    13441 ggatacattg tttcagtatt ttgaaatttt tcatttaatt tttataaatt ttctttttaa
    13501 attttagatt ctacaatatc tccaattctt cagtttattc cctcttacta tgtataagta
    13561 tttccccaag tttcacttta tctttctatt acttttttta cataatagag ctataaaggc
    13621 aattcacaat tctctctttt ctcatatata atatagagca tattataaat actctacttt
    13681 ggaaaattat tctttatagg aaattacaga taatatttga tgaagaaaat cgaatataat
    13741 catttttcaa tacttaggat aacagattca ggcaaagata aaacattaaa ggaaaagtta
    13801 gtgaaaacta ttaatatata gtggaggcat cacgttgtta tgaacttcat tgatcaatac
    13861 tgataccact aaaaatggaa caacatgtaa ttatgtgctc aatgtgatga atatgaagta
    13921 gactgcacca ctctgcagta cagtcaggaa ataagaaacc aagtccaatc aaaatagccc
    13981 taaagctacc ttccagttta taaaaagtat gaagaataga ggggcaatta aatgatacca
    14041 taaagagtca aatacagggc atgcaacata gctgctgatt ggatttattc aacatgtcag
    14101 tggcatgaat acaataggag gcaggtaggg agaaggcact accctgaatt atgagactga
    14161 agagatataa taaacaaatg caatgtgtgg acttggttgg gatcttcatt caaagaccaa
    14221 ctataaaaag acattgttgt gagaattgag gaaatttgaa tgagaaatgt atttttatct
    14281 aatttgttag ctgtgataat agtattgtgg gagtaagaag ctattcatat ttctatatat
    14341 atataccaag tacataggag tgaaataata caaaatctgg aatttgcctt aaaattcctc
    14401 tgcaaaatta taaaaaagaa cgatgacaaa ctaaaaaggt gtagtattct tctatggctg
    14461 ctataacaaa tgaccaaaaa acatagtgac tgaaaataac ccacatttat tatcttacag
    14521 ttccataggt tagaagttca acatgggtct catgagatca aaagcaaggc cttggcaggg
    14581 tgacgtttct ttctggaggt tccaggggga actctgtttt cttacttttt ttagattcta
    14641 gaggcttccc acaatccttg gcttaaggtc catctttaaa gacagcaacg tttcatctct
    14701 ctacctattc tttcatcctt acatctttct ctaactattc cttttcttct gtcttccact
    14761 tttaagagcc tttttgagtc tattgaggcc aactggacaa tcaaggatta tctccctatg
    14821 ttaaggtcaa ttgattagtg acctaattcc atctacaatc acaattcctc tttgccatat
    14881 aatgtaaaat attcatacct ctaaggatta ggacatggac atctttgagg gtcattagtc
    14941 atcttaccac aggaaggaag gaaggaagga aggaaggaag gaaggaagga aggaaggaag
    15001 gaaagggagg agaggagagg agaggtagga gggaagaaga aaaaaatagt atgaaaaaat
    15061 cttgataaat ttgaaaactg ggtgaataat atgtggaatt ctctctattt ttgttaatgt
    15121 tggaaaattt aataaaaaca atgaacagtg a
//
