LOCUS       NM_000379               5715 bp    mRNA    linear   PRI 11-FEB-2025
DEFINITION  Homo sapiens xanthine dehydrogenase (XDH), mRNA.
ACCESSION   NM_000379
VERSION     NM_000379.4
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 5715)
  AUTHORS   Massimo,G., Khambata,R.S., Chapman,T., Birchall,K., Raimondi,C.,
            Shabbir,A., Dyson,N., Rathod,K.S., Borghi,C. and Ahluwalia,A.
  TITLE     Natural mutations of human XDH promote the nitrite (NO2-)-reductase
            capacity of xanthine oxidoreductase: A novel mechanism to promote
            redox health?
  JOURNAL   Redox Biol 67, 102864 (2023)
   PUBMED   37713777
  REMARK    GeneRIF: Natural mutations of human XDH promote the nitrite
            (NO2[-])-reductase capacity of xanthine oxidoreductase: A novel
            mechanism to promote redox health?
            Erratum:[Redox Biol. 2023 Nov;67:102925. doi:
            10.1016/j.redox.2023.102925.. PMID: 37867029]
REFERENCE   2  (bases 1 to 5715)
  AUTHORS   Shimizu,M., Kasai,T., Naito,R., Sato,A., Ishiwata,S., Yatsu,S.,
            Shitara,J., Matsumoto,H., Murata,A., Kato,T., Suda,S., Hiki,M.,
            Kuwabara,M., Murase,T., Nakamura,T. and Daida,H.
  TITLE     Overnight changes in uric acid, xanthine oxidoreductase and
            oxidative stress levels and their relationships with
            sleep-disordered breathing in patients with coronary artery disease
  JOURNAL   Hypertens Res 46 (10), 2293-2301 (2023)
   PUBMED   37258622
  REMARK    GeneRIF: Overnight changes in uric acid, xanthine oxidoreductase
            and oxidative stress levels and their relationships with
            sleep-disordered breathing in patients with coronary artery
            disease.
REFERENCE   3  (bases 1 to 5715)
  AUTHORS   Gao,L., Rafaels,N., Dudenkov,T.M., Damarla,M., Damico,R.,
            Maloney,J.P., Moss,M., Martin,G.S., Sevransky,J., Shanholtz,C.,
            Herr,D.L., Garcia,J.G.N., Hernandez-Beeftink,T., Villar,J.,
            Flores,C., Beaty,T.H., Brower,R., Hassoun,P.M. and Barnes,K.C.
  TITLE     Xanthine oxidoreductase gene polymorphisms are associated with high
            risk of sepsis and organ failure
  JOURNAL   Respir Res 24 (1), 177 (2023)
   PUBMED   37415141
  REMARK    GeneRIF: Xanthine oxidoreductase gene polymorphisms are associated
            with high risk of sepsis and organ failure.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 5715)
  AUTHORS   Yu,H., Chen,X., Guo,X., Chen,D., Jiang,L., Qi,Y., Shao,J., Tao,L.,
            Hang,J., Lu,G., Chen,Y. and Li,Y.
  TITLE     The clinical value of serum xanthine oxidase levels in patients
            with acute ischemic stroke
  JOURNAL   Redox Biol 60, 102623 (2023)
   PUBMED   36739755
  REMARK    GeneRIF: The clinical value of serum xanthine oxidase levels in
            patients with acute ischemic stroke.
REFERENCE   5  (bases 1 to 5715)
  AUTHORS   Yamaguchi,Y., Matsumura,T., Ichida,K., Okamoto,K. and Nishino,T.
  TITLE     Human xanthine oxidase changes its substrate specificity to
            aldehyde oxidase type upon mutation of amino acid residues in the
            active site: roles of active site residues in binding and
            activation of purine substrate
  JOURNAL   J Biochem 141 (4), 513-524 (2007)
   PUBMED   17301077
  REMARK    GeneRIF: findings show that mutation of two amino acid residues in
            the active site of XOR for purine substrates results in conversion
            of the substrate preference to aldehyde oxidase type
            GeneRIF: Xanthine dehydrogenase/oxidase is a moonlighting protein
            that has two distinct catalytic activities as a dehydrogenase and
            an oxidase.
REFERENCE   6  (bases 1 to 5715)
  AUTHORS   Xu,P., Huecksteadt,T.P., Harrison,R. and Hoidal,J.R.
  TITLE     Molecular cloning, tissue expression of human xanthine
            dehydrogenase
  JOURNAL   Biochem Biophys Res Commun 215 (1), 429 (1995)
   PUBMED   7575623
  REMARK    Correction to:[Biochem Biophys Res Commun. 1994 Mar
            15;199(2):998-1004. doi: 10.1006/bbrc.1994.1328.. PMID: 8135849]
REFERENCE   7  (bases 1 to 5715)
  AUTHORS   Rytkonen,E.M., Halila,R., Laan,M., Saksela,M., Kallioniemi,O.P.,
            Palotie,A. and Raivio,K.O.
  TITLE     The human gene for xanthine dehydrogenase (XDH) is localized on
            chromosome band 2q22
  JOURNAL   Cytogenet Cell Genet 68 (1-2), 61-63 (1995)
   PUBMED   7956361
REFERENCE   8  (bases 1 to 5715)
  AUTHORS   Minoshima,S., Wang,Y., Ichida,K., Nishino,T. and Shimizu,N.
  TITLE     Mapping of the gene for human xanthine dehydrogenase (oxidase)
            (XDH) to band p23 of chromosome 2
  JOURNAL   Cytogenet Cell Genet 68 (1-2), 52-53 (1995)
   PUBMED   7956358
REFERENCE   9  (bases 1 to 5715)
  AUTHORS   Xu,P., Zhu,X.L., Huecksteadt,T.P., Brothman,A.R. and Hoidal,J.R.
  TITLE     Assignment of human xanthine dehydrogenase gene to chromosome 2p22
  JOURNAL   Genomics 23 (1), 289-291 (1994)
   PUBMED   7829092
REFERENCE   10 (bases 1 to 5715)
  AUTHORS   Ichikawa,M., Nishino,T., Nishino,T. and Ichikawa,A.
  TITLE     Subcellular localization of xanthine oxidase in rat hepatocytes:
            high-resolution immunoelectron microscopic study combined with
            biochemical analysis
  JOURNAL   J Histochem Cytochem 40 (8), 1097-1103 (1992)
   PUBMED   1619276
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL121654.1, D11456.2,
            AL121657.4 and CV574002.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000379.3.
            
            Summary: Xanthine dehydrogenase belongs to the group of
            molybdenum-containing hydroxylases involved in the oxidative
            metabolism of purines. The encoded protein has been identified as a
            moonlighting protein based on its ability to perform
            mechanistically distinct functions. Xanthine dehydrogenase can be
            converted to xanthine oxidase by reversible sulfhydryl oxidation or
            by irreversible proteolytic modification. Defects in xanthine
            dehydrogenase cause xanthinuria, may contribute to adult
            respiratory stress syndrome, and may potentiate influenza infection
            through an oxygen metabolite-dependent mechanism. [provided by
            RefSeq, Jan 2014].
            
            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 :: SRR14038191.4270634.1,
                                           SRR14038196.3290701.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1966682,
                                           SAMEA1968189 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match              :: ENST00000379416.4/
                                               ENSP00000368727.3
            multifunctional gene product(s) :: PMID: 17301077
            RefSeq Select criteria          :: based on conservation,
                                               expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-27                AL121654.1         31635-31661         c
            28-3105             D11456.2           9-3086
            3106-3106           AL121657.4         120308-120308       c
            3107-4408           D11456.2           3088-4389
            4409-5671           AL121657.4         105753-107015       c
            5672-5714           CV574002.1         318-360
            5715-5715           AL121657.4         105709-105709       c
FEATURES             Location/Qualifiers
     source          1..5715
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p23.1"
     gene            1..5715
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /note="xanthine dehydrogenase"
                     /db_xref="GeneID:7498"
                     /db_xref="HGNC:HGNC:12805"
                     /db_xref="MIM:607633"
     exon            1..118
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     CDS             77..4078
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /EC_number="1.17.1.4"
                     /EC_number="1.17.3.2"
                     /note="xanthine oxidoreductase"
                     /codon_start=1
                     /product="xanthine dehydrogenase/oxidase"
                     /protein_id="NP_000370.2"
                     /db_xref="CCDS:CCDS1775.1"
                     /db_xref="GeneID:7498"
                     /db_xref="HGNC:HGNC:12805"
                     /db_xref="MIM:607633"
                     /translation="MTADKLVFFVNGRKVVEKNADPETTLLAYLRRKLGLSGTKLGCG
                     EGGCGACTVMLSKYDRLQNKIVHFSANACLAPICSLHHVAVTTVEGIGSTKTRLHPVQ
                     ERIAKSHGSQCGFCTPGIVMSMYTLLRNQPEPTMEEIENAFQGNLCRCTGYRPILQGF
                     RTFARDGGCCGGDGNNPNCCMNQKKDHSVSLSPSLFKPEEFTPLDPTQEPIFPPELLR
                     LKDTPRKQLRFEGERVTWIQASTLKELLDLKAQHPDAKLVVGNTEIGIEMKFKNMLFP
                     MIVCPAWIPELNSVEHGPDGISFGAACPLSIVEKTLVDAVAKLPAQKTEVFRGVLEQL
                     RWFAGKQVKSVASVGGNIITASPISDLNPVFMASGAKLTLVSRGTRRTVQMDHTFFPG
                     YRKTLLSPEEILLSIEIPYSREGEYFSAFKQASRREDDIAKVTSGMRVLFKPGTTEVQ
                     ELALCYGGMANRTISALKTTQRQLSKLWKEELLQDVCAGLAEELHLPPDAPGGMVDFR
                     CTLTLSFFFKFYLTVLQKLGQENLEDKCGKLDPTFASATLLFQKDPPADVQLFQEVPK
                     GQSEEDMVGRPLPHLAADMQASGEAVYCDDIPRYENELSLRLVTSTRAHAKIKSIDTS
                     EAKKVPGFVCFISADDVPGSNITGICNDETVFAKDKVTCVGHIIGAVVADTPEHTQRA
                     AQGVKITYEELPAIITIEDAIKNNSFYGPELKIEKGDLKKGFSEADNVVSGEIYIGGQ
                     EHFYLETHCTIAVPKGEAGEMELFVSTQNTMKTQSFVAKMLGVPANRIVVRVKRMGGG
                     FGGKETRSTVVSTAVALAAYKTGRPVRCMLDRDEDMLITGGRHPFLARYKVGFMKTGT
                     VVALEVDHFSNVGNTQDLSQSIMERALFHMDNCYKIPNIRGTGRLCKTNLPSNTAFRG
                     FGGPQGMLIAECWMSEVAVTCGMPAEEVRRKNLYKEGDLTHFNQKLEGFTLPRCWEEC
                     LASSQYHARKSEVDKFNKENCWKKRGLCIIPTKFGISFTVPFLNQAGALLHVYTDGSV
                     LLTHGGTEMGQGLHTKMVQVASRALKIPTSKIYISETSTNTVPNTSPTAASVSADLNG
                     QAVYAACQTILKRLEPYKKKNPSGSWEDWVTAAYMDTVSLSATGFYRTPNLGYSFETN
                     SGNPFHYFSYGVACSEVEIDCLTGDHKNLRTDIVMDVGSSLNPAIDIGQVEGAFVQGL
                     GLFTLEELHYSPEGSLHTRGPSTYKIPAFGSIPIEFRVSLLRDCPNKKAIYASKAVGE
                     PPLFLAASIFFAIKDAIRAARAQHTGNNVKELFRLDSPATPEKIRNACVDKFTTLCVT
                     GVPENCKPWSVRV"
     exon            119..176
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            177..273
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            274..382
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            383..509
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            510..571
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            572..640
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            641..727
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            728..869
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            870..962
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            963..1114
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1115..1208
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1209..1318
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1319..1503
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1504..1678
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1679..1762
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1763..1932
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1933..2056
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            2057..2176
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            2177..2273
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            2274..2398
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            2399..2532
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            2533..2620
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            2621..2707
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            2708..2899
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            2900..3045
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            3046..3127
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            3128..3223
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            3224..3352
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            3353..3427
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            3428..3480
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            3481..3595
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            3596..3661
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            3662..3850
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            3851..4027
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     exon            4028..5715
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5694..5699
                     /regulatory_class="polyA_signal_sequence"
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /note="hexamer: AATAAA"
     polyA_site      5715
                     /gene="XDH"
                     /gene_synonym="XAN1; XO; XOR"
                     /note="major polyA site"
ORIGIN      
        1 acagagcagt gataactacc tgccagtgtc tcttaggagt gaggtacctg gagttcgggg
       61 accccaacct gtgacaatga cagcagacaa attggttttc tttgtgaatg gcagaaaggt
      121 ggtggagaaa aatgcagatc cagagacaac ccttttggcc tacctgagaa gaaagttggg
      181 gctgagtgga accaagctcg gctgtggaga ggggggctgc ggggcttgca cagtgatgct
      241 ctccaagtat gatcgtctgc agaacaagat cgtccacttt tctgccaatg cctgcctggc
      301 ccccatctgc tccttgcacc atgttgcagt gacaactgtg gaaggaatag gaagcaccaa
      361 gacgaggctg catcctgtgc aggagagaat tgccaaaagc cacggctccc agtgcgggtt
      421 ctgcacccct ggcatcgtca tgagtatgta cacactgctc cggaatcagc ccgagcccac
      481 catggaggag attgagaatg ccttccaagg aaatctgtgc cgctgcacag gctacagacc
      541 catcctccag ggcttccgga cctttgccag ggatggtgga tgctgtggag gagatgggaa
      601 taatccaaat tgctgcatga accagaagaa agaccactca gtcagcctct cgccatcttt
      661 attcaaacca gaggagttca cgcccctgga tccaacccag gagcccattt ttcccccaga
      721 gttgctgagg ctgaaagaca ctcctcggaa gcagctgcga tttgaagggg agcgtgtgac
      781 gtggatacag gcctcaaccc tcaaggagct gctggacctc aaggctcagc accctgacgc
      841 caagctggtc gtggggaaca cggagattgg cattgagatg aagttcaaga atatgctgtt
      901 tcctatgatt gtctgcccag cctggatccc tgagctgaat tcggtagaac atggacccga
      961 cggtatctcc tttggagctg cttgccccct gagcattgtg gaaaaaaccc tggtggatgc
     1021 tgttgctaag cttcctgccc aaaagacaga ggtgttcaga ggggtcctgg agcagctgcg
     1081 ctggtttgct gggaagcaag tcaagtctgt ggcgtccgtt ggagggaaca tcatcactgc
     1141 cagccccatc tccgacctca accccgtgtt catggccagt ggggccaagc tgacacttgt
     1201 gtccagaggc accaggagaa ctgtccagat ggaccacacc ttcttccctg gctacagaaa
     1261 gaccctgctg agcccggagg agatactgct ctccatagag atcccctaca gcagggaggg
     1321 ggagtatttc tcagcattca agcaggcctc ccggagagaa gatgacattg ccaaggtaac
     1381 cagtggcatg agagttttat tcaagccagg aaccacagag gtacaggagc tggccctttg
     1441 ctatggtgga atggccaaca gaaccatctc agccctcaag accactcaga ggcagctttc
     1501 caagctctgg aaggaggagc tgctgcagga cgtgtgtgca ggactggcag aggagctgca
     1561 tctgcctccc gatgcccctg gtggcatggt ggacttccgg tgcaccctca ccctcagctt
     1621 cttcttcaag ttctacctga cagtccttca gaagctgggc caagagaacc tggaagacaa
     1681 gtgtggtaaa ctggacccca ctttcgccag tgcaacttta ctgtttcaga aagacccccc
     1741 agccgatgtc cagctcttcc aagaggtgcc caagggtcag tctgaggagg acatggtggg
     1801 ccggcccctg ccccacctgg cagcggacat gcaggcctct ggtgaggccg tgtactgtga
     1861 cgacattcct cgctacgaga atgagctgtc tctccggctg gtcaccagca cccgggccca
     1921 cgccaagatc aagtccatag atacatcaga agctaagaag gttccagggt ttgtttgttt
     1981 catttccgct gatgatgttc ctgggagtaa cataactgga atttgtaatg atgagacagt
     2041 ctttgcgaag gataaggtta cttgtgttgg gcatatcatt ggtgctgtgg ttgctgacac
     2101 cccggaacac acacagagag ctgcccaagg ggtgaaaatc acctatgaag aactaccagc
     2161 cattatcaca attgaggatg ctataaagaa caactccttt tatggacctg agctgaagat
     2221 cgagaaaggg gacctaaaga aggggttttc cgaagcagat aatgttgtgt caggggagat
     2281 atacatcggt ggccaagagc acttctacct ggagactcac tgcaccattg ctgttccaaa
     2341 aggcgaggca ggggagatgg agctctttgt gtctacacag aacaccatga agacccagag
     2401 ctttgttgca aaaatgttgg gggttccagc aaaccggatt gtggttcgag tgaagagaat
     2461 gggaggaggc tttggaggca aggagacccg gagcactgtg gtgtccacgg cagtggccct
     2521 ggctgcatat aagaccggcc gccctgtgcg atgcatgctg gaccgtgatg aggacatgct
     2581 gataactggt ggcagacatc ccttcctggc cagatacaag gttggcttca tgaagactgg
     2641 gacagttgtg gctcttgagg tggaccactt cagcaatgtg gggaacaccc aggatctctc
     2701 tcagagtatt atggaacgag ctttattcca catggacaac tgctataaaa tccccaacat
     2761 ccggggcact gggcggctgt gcaaaaccaa ccttccctcc aacacggcct tccggggctt
     2821 tggggggccc caggggatgc tcattgccga gtgctggatg agtgaagttg cagtgacctg
     2881 tgggatgcct gcagaggagg tgcggagaaa aaacctgtac aaagaagggg acctgacaca
     2941 cttcaaccag aagcttgagg gtttcacctt gcccagatgc tgggaagaat gcctagcaag
     3001 ctctcagtat catgctcgga agagtgaggt tgacaagttc aacaaggaga attgttggaa
     3061 aaagagagga ttgtgcataa ttcccaccaa gtttggaata agctttacag ttccttttct
     3121 gaatcaggca ggagccctac ttcatgtgta cacagatggc tctgtgctgc tgacccacgg
     3181 ggggactgag atgggccaag gccttcatac caaaatggtc caggtggcca gtagagctct
     3241 gaaaatcccc acctctaaga tttatatcag cgagacaagc actaacactg tgcccaacac
     3301 ctctcccacg gctgcctctg tcagcgctga cctcaatgga caggccgtct atgcggcttg
     3361 tcagaccatc ttgaaaaggc tggaacccta caagaagaag aatcccagtg gctcctggga
     3421 agactgggtc acagctgcct acatggacac agtgagcttg tctgccactg ggttttatag
     3481 aacacccaat ctgggctaca gctttgagac taactcaggg aaccccttcc actacttcag
     3541 ctatggggtg gcttgctctg aagtagaaat cgactgccta acaggagatc ataagaacct
     3601 ccgcacagat attgtcatgg atgttggctc cagtctaaac cctgccattg atattggaca
     3661 ggtggaaggg gcatttgtcc agggccttgg cctcttcacc ctagaggagc tacactattc
     3721 ccccgagggg agcctgcaca cccgtggccc tagcacctac aagatcccgg catttggcag
     3781 catccccatt gagttcaggg tgtccctgct ccgcgactgc cccaacaaga aggccatcta
     3841 tgcatcgaag gctgttggag agccgcccct cttcctggct gcttctatct tctttgccat
     3901 caaagatgcc atccgtgcag ctcgagctca gcacacaggt aataacgtga aggaactctt
     3961 ccggctagac agccctgcca ccccggagaa gatccgcaat gcctgcgtgg acaagttcac
     4021 caccctgtgt gtcactggtg tcccagaaaa ctgcaaaccc tggtctgtga gggtctaaag
     4081 agagagtcct cagcagagtc ttcttgtgct gcctttgggc ttccatggag caggaggaac
     4141 ataccacaga acatggatct attaaagtca cagaatgaca gacctgtgat ttgtcaagat
     4201 gggatttgga agacaagtga atgcaatgga agattttgat caaaaatgta atttgtaaac
     4261 acaatgataa gcaaattcaa aactgttatg cctaaatggt gaatatgcaa ttaggatcat
     4321 tttctgtctg ttttaatcat gtatctggaa tagggtcggg aagggtttgt gctattcccc
     4381 acttactgga cagcctgtat aacctcaagt tctgatggtg tctgtccttt gaagaggatt
     4441 cccacaaacc tctagaagct taaaccgaag ttactttaaa tcgtgtgcct tcctgtgaaa
     4501 gcctggcctt caaaccaatg aacagcaaag cataaccttg aatctatact caaattttgc
     4561 aatgaggcag tggggtaagg ttaaatcctc taaccatctt tgaatcattg gaaagaataa
     4621 agaatgaaac aaattcaagg ttaattggat ctgattttgt gaagctgcat aaagcaagat
     4681 tactctataa tacaaaaatc caaccaactc aattattgag cacgtacaat gttctagatt
     4741 tctttccctt cctctttgaa gagaatattt gtattccaaa tactctttga gtatttacaa
     4801 aaaagattat gtttaatctt tacatttgaa gccaaagtaa tttccaccta gaaatgatgc
     4861 tatcagtcct ggcatggtgg ctcaccccta taatcccagc actttgggag gctaaggcag
     4921 gagaattgct tgagcccagc agtttgagac cagcctgggc aacatagaga gctcctgtct
     4981 ttaaaaaaaa tttttttaat tagttggtct tgatagtgca tgcctgtagt cccaactact
     5041 tgaaaggctg aggtggagag atcatttgag ctcaggaggt tgaggctgca gtgagctatg
     5101 attgcgccac tgcactcctg cctgagcgac tgagcaagat cttgtctctg aagaaaaaaa
     5161 aagaaataaa aatgctgcta tcaaaatcaa gcccaaccag aggtagaaga gccaagaagc
     5221 ctgggttctc atcctagctc tgtctcttct gtctctatct ttgtgatctt ggactgtcaa
     5281 ttccccttcc tgtgatccat tttactgcaa acataagggt tgcagtaaag ggttgtctca
     5341 cgtcttctgc tttaaaagcc tataaatata tgacctgaaa actccagtta cataaaggat
     5401 ctgcagctat ctaaggcttg gttttcttac tgtcatatga tacctgggtc taatgaactc
     5461 tgctgagatc acctcaagtt tctgcggttg gtaaagagaa caagggaaga acaaacatcc
     5521 cttttattgc tccaaatggt gatttaatcc ctacatggtg ctgggtggac aatgtgtcac
     5581 tgtcacatgc cttcactgta taaatccaac cttctgccag agagaatctg tggttctggc
     5641 catggaggga ggatagtgga aatgatatag ttggactggt gcttgatgtc actaataaat
     5701 gaaactgtca gctgg
//
