LOCUS       NM_000254              10547 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens 5-methyltetrahydrofolate-homocysteine
            methyltransferase (MTR), transcript variant 1, mRNA.
ACCESSION   NM_000254
VERSION     NM_000254.3
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 10547)
  AUTHORS   Du,W., Liu,L., Li,F. and Xu,S.
  TITLE     Genetic Association between the Risk of Dental Caries and MTR Gene
            Polymorphism in Chinese Children
  JOURNAL   Tohoku J Exp Med 263 (1), 63-68 (2024)
   PUBMED   38325832
  REMARK    GeneRIF: Genetic Association between the Risk of Dental Caries and
            MTR Gene Polymorphism in Chinese Children.
REFERENCE   2  (bases 1 to 10547)
  AUTHORS   Pawlik,P., Kurzawinska,G., Ozarowski,M., Wolski,H., Piatek,K.,
            Slopien,R., Sajdak,S., Olbromski,P. and Seremak-Mrozikiewicz,A.
  TITLE     Common Variants in One-Carbon Metabolism Genes (MTHFR, MTR, MTHFD1)
            and Depression in Gynecologic Cancers
  JOURNAL   Int J Mol Sci 24 (16), 12574 (2023)
   PUBMED   37628752
  REMARK    GeneRIF: Common Variants in One-Carbon Metabolism Genes (MTHFR,
            MTR, MTHFD1) and Depression in Gynecologic Cancers.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 10547)
  AUTHORS   Antunes,L.A.A., Fialho,W., Fernandes,T.O., Duarte,C.,
            Tavares,J.D.S., Kuchler,E.C. and Antunes,L.S.
  TITLE     Association of MTR and MTRR genes and oral health-related quality
            of life in children with dental caries
  JOURNAL   Braz Oral Res 37, e076 (2023)
   PUBMED   37531512
  REMARK    GeneRIF: Association of MTR and MTRR genes and oral health-related
            quality of life in children with dental caries.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 10547)
  AUTHORS   Liu,Y., Zhong,T., Song,X., Zhang,S., Sun,M., Wei,J., Shu,J.,
            Yang,T., Wang,T. and Qin,J.
  TITLE     Association of MTR gene polymorphisms with the occurrence of
            non-syndromic congenital heart disease: a case-control study
  JOURNAL   Sci Rep 13 (1), 9424 (2023)
   PUBMED   37296303
  REMARK    GeneRIF: Association of MTR gene polymorphisms with the occurrence
            of non-syndromic congenital heart disease: a case-control study.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 10547)
  AUTHORS   Col,B., Oltean,S. and Banerjee,R.
  TITLE     Translational regulation of human methionine synthase by upstream
            open reading frames
  JOURNAL   Biochim Biophys Acta 1769 (9-10), 532-540 (2007)
   PUBMED   17683808
REFERENCE   6  (bases 1 to 10547)
  AUTHORS   Sloan,J.L., Carrillo,N., Adams,D. and Venditti,C.P.
  TITLE     Disorders of Intracellular Cobalamin Metabolism
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301503
REFERENCE   7  (bases 1 to 10547)
  AUTHORS   Garovic-Kocic,V. and Rosenblatt,D.S.
  TITLE     Methionine auxotrophy in inborn errors of cobalamin metabolism
  JOURNAL   Clin Invest Med 15 (4), 395-400 (1992)
   PUBMED   1516297
REFERENCE   8  (bases 1 to 10547)
  AUTHORS   Everman,B.W. and Koblin,D.D.
  TITLE     Aging, chronic administration of ethanol, and acute exposure to
            nitrous oxide: effects on vitamin B12 and folate status in rats
  JOURNAL   Mech Ageing Dev 62 (3), 229-243 (1992)
   PUBMED   1583909
REFERENCE   9  (bases 1 to 10547)
  AUTHORS   O'Connor,D.L., Moriarty,P. and Picciano,M.F.
  TITLE     The impact of iron deficiency on the flux of folates within the
            mammary gland
  JOURNAL   Int J Vitam Nutr Res 62 (2), 173-180 (1992)
   PUBMED   1517041
REFERENCE   10 (bases 1 to 10547)
  AUTHORS   Vassiliadis,A., Rosenblatt,D.S., Cooper,B.A. and Bergeron,J.J.
  TITLE     Lysosomal cobalamin accumulation in fibroblasts from a patient with
            an inborn error of cobalamin metabolism (cblF complementation
            group): visualization by electron microscope radioautography
  JOURNAL   Exp Cell Res 195 (2), 295-302 (1991)
   PUBMED   2070814
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL359185.25 and AL359259.18.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 21, 2020 this sequence version replaced NM_000254.2.
            
            Summary: This gene encodes the
            5-methyltetrahydrofolate-homocysteine methyltransferase. This
            enzyme, also known as cobalamin-dependent methionine synthase,
            catalyzes the final step in methionine biosynthesis. Mutations in
            MTR have been identified as the underlying cause of methylcobalamin
            deficiency complementation group G. Alternatively spliced
            transcript variants encoding distinct isoforms have been found for
            this gene. [provided by RefSeq, May 2014].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            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.
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000366577.10/ ENSP00000355536.5
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            regulatory uORF        :: PMID: 17683808
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-446               AL359185.25        60634-61079
            447-661             AL359185.25        68770-68984
            662-751             AL359185.25        71486-71575
            752-821             AL359185.25        74046-74115
            822-914             AL359185.25        75845-75937
            915-1021            AL359185.25        78080-78186
            1022-1081           AL359185.25        80946-81005
            1082-1176           AL359185.25        81791-81885
            1177-1277           AL359185.25        89461-89561
            1278-1339           AL359185.25        90680-90741
            1340-1407           AL359185.25        92171-92238
            1408-1487           AL359185.25        94531-94610
            1488-1600           AL359185.25        97308-97420
            1601-1741           AL359185.25        100889-101029
            1742-1927           AL359185.25        103756-103941
            1928-2107           AL359259.18        8845-9024
            2108-2224           AL359259.18        11022-11138
            2225-2365           AL359259.18        11449-11589
            2366-2455           AL359259.18        18334-18423
            2456-2608           AL359259.18        19626-19778
            2609-2716           AL359259.18        20737-20844
            2717-2817           AL359259.18        21955-22055
            2818-2885           AL359259.18        32274-32341
            2886-3006           AL359259.18        33227-33347
            3007-3088           AL359259.18        39256-39337
            3089-3187           AL359259.18        43622-43720
            3188-3263           AL359259.18        44793-44868
            3264-3419           AL359259.18        47682-47837
            3420-3616           AL359259.18        49634-49830
            3617-3817           AL359259.18        52858-53058
            3818-4010           AL359259.18        53859-54051
            4011-4123           AL359259.18        55507-55619
            4124-10547          AL359259.18        56059-62482
FEATURES             Location/Qualifiers
     source          1..10547
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q43"
     gene            1..10547
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /note="5-methyltetrahydrofolate-homocysteine
                     methyltransferase"
                     /db_xref="GeneID:4548"
                     /db_xref="HGNC:HGNC:7468"
                     /db_xref="MIM:156570"
     exon            1..446
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      30..455
                     /regulatory_class="uORF"
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:17683808]"
                     /note="this uORF is predicted to encode a 141 aa peptide
                     (PMID:17683808)"
     regulatory      53..145
                     /regulatory_class="uORF"
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:17683808]"
                     /note="this uORF is predicted to encode a 30 aa peptide
                     (PMID:17683808)"
     CDS             413..4210
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /EC_number="2.1.1.13"
                     /note="isoform 1 is encoded by transcript variant 1;
                     5-methyltetrahydrofolate-homocysteine methyltransferase 1;
                     vitamin-B12 dependent methionine synthase;
                     cobalamin-dependent methionine synthase"
                     /codon_start=1
                     /product="methionine synthase isoform 1"
                     /protein_id="NP_000245.2"
                     /db_xref="CCDS:CCDS1614.1"
                     /db_xref="GeneID:4548"
                     /db_xref="HGNC:HGNC:7468"
                     /db_xref="MIM:156570"
                     /translation="MSPALQDLSQPEGLKKTLRDEINAILQKRIMVLDGGMGTMIQRE
                     KLNEEHFRGQEFKDHARPLKGNNDILSITQPDVIYQIHKEYLLAGADIIETNTFSSTS
                     IAQADYGLEHLAYRMNMCSAGVARKAAEEVTLQTGIKRFVAGALGPTNKTLSVSPSVE
                     RPDYRNITFDELVEAYQEQAKGLLDGGVDILLIETIFDTANAKAALFALQNLFEEKYA
                     PRPIFISGTIVDKSGRTLSGQTGEGFVISVSHGEPLCIGLNCALGAAEMRPFIEIIGK
                     CTTAYVLCYPNAGLPNTFGDYDETPSMMAKHLKDFAMDGLVNIVGGCCGSTPDHIREI
                     AEAVKNCKPRVPPATAFEGHMLLSGLEPFRIGPYTNFVNIGERCNVAGSRKFAKLIMA
                     GNYEEALCVAKVQVEMGAQVLDVNMDDGMLDGPSAMTRFCNLIASEPDIAKVPLCIDS
                     SNFAVIEAGLKCCQGKCIVNSISLKEGEDDFLEKARKIKKYGAAMVVMAFDEEGQATE
                     TDTKIRVCTRAYHLLVKKLGFNPNDIIFDPNILTIGTGMEEHNLYAINFIHATKVIKE
                     TLPGARISGGLSNLSFSFRGMEAIREAMHGVFLYHAIKSGMDMGIVNAGNLPVYDDIH
                     KELLQLCEDLIWNKDPEATEKLLRYAQTQGTGGKKVIQTDEWRNGPVEERLEYALVKG
                     IEKHIIEDTEEARLNQKKYPRPLNIIEGPLMNGMKIVGDLFGAGKMFLPQVIKSARVM
                     KKAVGHLIPFMEKEREETRVLNGTVEEEDPYQGTIVLATVKGDVHDIGKNIVGVVLGC
                     NNFRVIDLGVMTPCDKILKAALDHKADIIGLSGLITPSLDEMIFVAKEMERLAIRIPL
                     LIGGATTSKTHTAVKIAPRYSAPVIHVLDASKSVVVCSQLLDENLKDEYFEEIMEEYE
                     DIRQDHYESLKERRYLPLSQARKSGFQMDWLSEPHPVKPTFIGTQVFEDYDLQKLVDY
                     IDWKPFFDVWQLRGKYPNRGFPKIFNDKTVGGEARKVYDDAHNMLNTLISQKKLRARG
                     VVGFWPAQSIQDDIHLYAEAAVPQAAEPIATFYGLRQQAEKDSASTEPYYCLSDFIAP
                     LHSGIRDYLGLFAVACFGVEELSKAYEDDGDDYSSIMVKALGDRLAEAFAEELHERVR
                     RELWAYCGSEQLDVADLRRLRYKGIRPAPGYPSQPDHTEKLTMWRLADIEQSTGIRLT
                     ESLAMAPASAVSGLYFSNLKSKYFAVGKISKDQVEDYALRKNISVAEVEKWLGPILGY
                     DTD"
     exon            447..661
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            662..751
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            752..821
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            822..914
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            915..1021
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            1022..1081
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            1082..1176
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            1177..1277
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            1278..1339
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            1340..1407
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            1408..1487
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            1488..1600
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            1601..1741
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            1742..1927
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            1928..2107
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            2108..2224
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            2225..2365
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            2366..2455
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            2456..2608
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            2609..2716
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            2717..2817
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            2818..2885
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            2886..3006
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            3007..3088
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            3089..3187
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            3188..3263
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            3264..3419
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            3420..3616
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            3617..3817
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            3818..4010
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            4011..4123
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     exon            4124..10547
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      7207..7212
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /note="hexamer: AATAAA"
     polyA_site      7237
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /note="major polyA site"
     regulatory      10480..10485
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /note="hexamer: AATAAA"
     polyA_site      10499
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
     regulatory      10527..10532
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
                     /note="hexamer: ATTAAA"
     polyA_site      10547
                     /gene="MTR"
                     /gene_synonym="cblG; HMAG; MS"
ORIGIN      
        1 agaactaacc gcgctctgaa aggttctaaa tgtctgcggg gctcagagcc ggatgtcacg
       61 tcgtcctcct ctgccggttt tctcttgggt ccttttccgt gccgtcccgc gactccgcct
      121 ctggccgcgc gtgtctggct gctaggccga caccaaggac tggccgggta cccgggaaga
      181 aagcacgtgc tccagcagtt gccgcgccca gccccgagag aggccctagg gcgctgcggg
      241 ctttcggggt ccgcagtccc cccgcgacgc gagccaacgg gaggcgtcaa aagacccggg
      301 ccttgtgtgg caggctcgcc tggcgctggc tggcgtggcc cttggccgtc gtcacctgtg
      361 gagagcacgt cttctctgcc gcgccctctg cgcaaggagg agactcgaca acatgtcacc
      421 cgcgctccaa gacctgtcgc aacccgaagg tctgaagaaa accctgcggg atgagatcaa
      481 tgccattctg cagaagagga ttatggtgct ggatggaggg atggggacca tgatccagcg
      541 ggagaagcta aacgaagaac acttccgagg tcaggaattt aaagatcatg ccaggccgct
      601 gaaaggcaac aatgacattt taagtataac tcagcctgat gtcatttacc aaatccataa
      661 ggaatacttg ctggctgggg cagatatcat tgaaacaaat acttttagca gcactagtat
      721 tgcccaagct gactatggcc ttgaacactt ggcctaccgg atgaacatgt gctctgcagg
      781 agtggccaga aaagctgccg aggaggtaac tctccagaca ggaattaaga ggtttgtggc
      841 aggggctctg ggtccgacta ataagacact ctctgtgtcc ccatctgtgg aaaggccgga
      901 ttataggaac atcacatttg atgagcttgt tgaagcatac caagagcagg ccaaaggact
      961 tctggatggc ggggttgata tcttactcat tgaaactatt tttgatactg ccaatgccaa
     1021 ggcagccttg tttgcactcc aaaatctttt tgaggagaaa tatgctcccc ggcctatctt
     1081 tatttcaggg acgatcgttg ataaaagtgg gcggactctt tccggacaga caggagaggg
     1141 atttgtcatc agcgtgtctc atggagaacc actctgcatt ggattaaatt gtgctttggg
     1201 tgcagctgaa atgagacctt ttattgaaat aattggaaaa tgtacaacag cctatgtcct
     1261 ctgttatccc aatgcaggtc ttcccaacac ctttggtgac tatgatgaaa cgccttctat
     1321 gatggccaag cacctaaagg attttgctat ggatggcttg gtcaatatag ttggaggatg
     1381 ctgtgggtca acaccagatc atatcaggga aattgctgaa gctgtgaaaa attgtaagcc
     1441 tagagttcca cctgccactg cttttgaagg acatatgtta ctgtctggtc tagagccctt
     1501 caggattgga ccgtacacca actttgttaa cattggagag cgctgtaatg ttgcaggatc
     1561 aaggaagttt gctaaactca tcatggcagg aaactatgaa gaagccttgt gtgttgccaa
     1621 agtgcaggtg gaaatgggag cccaggtgtt ggatgtcaac atggatgatg gcatgctaga
     1681 tggtccaagt gcaatgacca gattttgcaa cttaattgct tccgagccag acatcgcaaa
     1741 ggtacctttg tgcatcgact cctccaattt tgctgtgatt gaagctgggt taaagtgctg
     1801 ccaagggaag tgcattgtca atagcattag tctgaaggaa ggagaggacg acttcttgga
     1861 gaaggccagg aagattaaaa agtatggagc tgctatggtg gtcatggctt ttgatgaaga
     1921 aggacaggca acagaaacag acacaaaaat cagagtgtgc acccgggcct accatctgct
     1981 tgtgaaaaaa ctgggcttta atccaaatga cattattttt gaccctaata tcctaaccat
     2041 tgggactgga atggaggaac acaacttgta tgccattaat tttatccatg caacaaaagt
     2101 cattaaagaa acattacctg gagccagaat aagtggaggt ctttccaact tgtccttctc
     2161 cttccgagga atggaagcca ttcgagaagc aatgcatggg gttttccttt accatgcaat
     2221 caagtctggc atggacatgg ggatagtgaa tgctggaaac ctccctgtgt atgatgatat
     2281 ccataaggaa cttctgcagc tctgtgaaga tctcatctgg aataaagacc ctgaggccac
     2341 tgagaagctc ttacgttatg cccagactca aggcacagga gggaagaaag tcattcagac
     2401 tgatgagtgg agaaatggcc ctgtcgaaga acgccttgag tatgcccttg tgaagggcat
     2461 tgaaaaacat attattgagg atactgagga agccaggtta aaccaaaaaa aatatccccg
     2521 acctctcaat ataattgaag gacccctgat gaatggaatg aaaattgttg gtgatctttt
     2581 tggagctgga aaaatgtttc tacctcaggt tataaagtca gcccgggtta tgaagaaggc
     2641 tgttggccac cttatccctt tcatggaaaa agaaagagaa gaaaccagag tgcttaacgg
     2701 cacagtagaa gaagaggacc cttaccaggg caccatcgtg ctggccactg ttaaaggcga
     2761 cgtgcacgac ataggcaaga acatagttgg agtagtcctt ggctgcaata atttccgagt
     2821 tattgattta ggagtcatga ctccatgtga taagatactg aaagctgctc ttgaccacaa
     2881 agcagatata attggcctgt caggactcat cactccttcc ctggatgaaa tgatttttgt
     2941 tgccaaggaa atggagagat tagctataag gattccattg ttgattggag gagcaaccac
     3001 ttcaaaaacc cacacagcag ttaaaatagc tccgagatac agtgcacctg taatccatgt
     3061 cctggacgcg tccaagagtg tggtggtgtg ttcccagctg ttagatgaaa atctaaagga
     3121 tgaatacttt gaggaaatca tggaagaata tgaagatatt agacaggacc attatgagtc
     3181 tctcaaggag aggagatact tacccttaag tcaagccaga aaaagtggtt tccaaatgga
     3241 ttggctgtct gaacctcacc cagtgaagcc cacgtttatt gggacccagg tctttgaaga
     3301 ctatgacctg cagaagctgg tggactacat tgactggaag cctttctttg atgtctggca
     3361 gctccggggc aagtacccga atcgaggctt tcccaagata tttaacgaca aaacagtagg
     3421 tggagaggcc aggaaggtct acgatgatgc ccacaatatg ctgaacacac tgattagtca
     3481 aaagaaactc cgggcccggg gtgtggttgg gttctggcca gcacagagta tccaagacga
     3541 cattcacctg tacgcagagg ctgctgtgcc ccaggctgca gagcccatag ccaccttcta
     3601 tgggttaagg caacaggctg agaaggactc tgccagcacg gagccatact actgcctctc
     3661 agacttcatc gctcccttgc attctggcat ccgtgactac ctgggcctgt ttgccgttgc
     3721 ctgctttggg gtagaagagc tgagcaaggc ctatgaggat gatggtgacg actacagcag
     3781 catcatggtc aaggcgctgg gggaccggct ggcagaggcc tttgcagaag agctccatga
     3841 aagagttcgc cgagaactgt gggcctactg tggcagtgag cagctggacg tcgcagacct
     3901 gcgcaggctg cggtacaagg gcatccgccc ggctcctggc taccccagcc agcccgacca
     3961 caccgagaag ctcaccatgt ggagactcgc agacatcgag cagtctacag gcattaggtt
     4021 aacagaatca ttagcaatgg cacctgcttc agcagtctca ggcctctact tctccaattt
     4081 gaagtccaaa tattttgctg tggggaagat ttccaaggat caggttgagg attatgcatt
     4141 gaggaagaac atatctgtgg ctgaggttga gaaatggctt ggacccattt tgggatatga
     4201 tacagactaa cttttttttt ttttttgcct tttttattct tgatgatcct caaggaaata
     4261 caacctaggg tgccttaaaa ataacaacaa caaaaaacct gtgtgcatct ggctgacact
     4321 tacctgcttc tggttttcga agactattta gtggaacctt gtagaggagc agggtcttcc
     4381 tgcagtgcct ggaaaacagg cgctgttttt ttgggacctt gcgtgaagag cagtgagcag
     4441 ggttcctgtg gtttccctgg tccctctgag atggggacag actgaagaca gaggtcgttt
     4501 gatttcaaag caagtcaacc tgcttttttc tgtttttaca gtggaatcta ggaggccact
     4561 tagtcgtctt tttttcctct tagaagaaaa gcctgaaact gagttgaata gagaagtgtg
     4621 accctgtgac aaaatgatac tgtgagaaat ggggcatttt aatctaagtg gttataacag
     4681 tggattctga cggggaaggt gtagctctgt tctcttcgga agacctcgtt ttctaaaggc
     4741 tggactaaat ggctgcagaa ctccctttgg caaaaggcat gcgctcactg cttgcttgtc
     4801 agaaacactg aagccatttg ccccagtgtg gtcaagcagc catgctttct gggcattttc
     4861 gtcctcccat aatttcatat ttccgtaccc ctgaggaaac aaaaaggaaa tgaggagaga
     4921 aagttactgt taagggtggt taacattttt tttgttttgt tttgttttgg tttttttttt
     4981 tttgagacag agtctggctc tgtcgcccag gctggagtgc aggggcgcaa tctcggctca
     5041 tagcaagctc cgcctcctgg gttcatgcca ttctcctgcc tcagcctcca gagtagctgg
     5101 gactacaggt gcccgccacc acacccggct aattttttgt gtttttacaa aatacaaaaa
     5161 agtagagaca ggatttcact gtgttagcca ggatggtctt gatctcccga cctcgtgatc
     5221 tgcccacctc agcctcccaa aatgctggga ttacaggcgt gagccaccga gcctggccgg
     5281 ttaacatctt ttaattgttt ccaggattga gcaggttctc agctgggctc tgatatcccg
     5341 tgcggagttg gacaagtggg cagcataaag tcactcattt cttaccattt tattcccctc
     5401 aattctcaat atattcagta atgaagaatg gtgccaccac tcaagcaaca agcctcaaac
     5461 tcaaccatgt catctttttc ttggatgatt gcagttattt caaaaatttg catgcaaaat
     5521 atacactcat cctacttcaa gatggtggtg gcaatagtca ggagaaggta acattggagt
     5581 cctggtttga ttcgaaggat gaagacgaag aagcaaggga ggaacaaatg aagaaccatc
     5641 tttgttcatg aataggaata ttcaagatta taaaggtatc aggtctccta aaattgatct
     5701 atggatttaa taccattttc aatggaaatt ccaacagatt ttattgaatg aaacaagcag
     5761 gtgtttatat ggagtagcaa aggacttaaa attaccaaat gcttctaaat atgaaggaga
     5821 ggttggggac acgcacccta tgtgatacca agttttattg tcaagacagt gtcatggtgc
     5881 agaggtaggc attctgagca ggggaacaaa ataagggcct agaaactcac ccgtgcatat
     5941 gttgaccttt gcaaaatgac ctggtgacat ggcaagtcag tggggacagg aaggaccact
     6001 ccctaagtaa tcccagaaca atggctattc atgtgggaaa aaaagaaatt ttactttctc
     6061 tcaccttacc tggtgataag ttccaaatat gttaagggct ttaatacaaa aagcaaaaat
     6121 tgtcagtgtt tggatgaaaa aagccttagg gcaggaaaga atctcttgag acataaagta
     6181 gtaatcataa aggacaagat ggttaagtca attctgttaa aactcaaggc ttatattaag
     6241 caaacacttg aagtgagaag atgatccaca acttgagaag acatttataa tacaaataac
     6301 tgatgaagga ttcataatca caaatataga gaattcctat ttaaaaaaat agaaaaatag
     6361 tgaagactac acaagaggaa atagggcttt taaataaata gatgttctgt agcattggtc
     6421 agggaaatat gaattaggac cacaatgaga ttccatttta tatccataag atttgcaaag
     6481 gttgggtctg acagtaccag ttgttagatc tgtagggact tgtacaacat tgtggatgtg
     6541 taaacaggca ccactgcttt aaaaaacaat tatcccttac agacttgaac atttgcagac
     6601 gttatgatct tgcttccaac tcccacctgt atgtccagca aactcttgca tgtggccact
     6661 aggaggaatg tgtaagaatg ttcatagtta catatttata atagttaata actggaaaaa
     6721 gtgaaatgta tgtctgtcta caggaaaata ggtgaataat tagatatata tattcattct
     6781 acgggatatt attcagtagt ggaaatgagt gaactacagc tatacctcac aataagaatg
     6841 aatctcagaa aatattaagg aaaaaagcaa gtttgaagag accacatggg gcgtactatt
     6901 tttattgagc ccaaaaacaa gcaaaaccaa agaatatgta gtctaagcat acgtatacaa
     6961 taaaactatg ctattaaaaa aaaagaaggt aactgataaa ccaaaattga gcatagtaat
     7021 tacccacaga aggaggaagt ggaagggaca ggagcacata ggtagatgcc aagttatgca
     7081 gctgttctgg ttcctcctgg taggcttaca agtgtttact atatgctatt aatacattat
     7141 actttataac taatagataa cagtttttta catattaaat atgttctact taaatatatt
     7201 ataaaaaata aaggcaaagt ggaatgataa cctaaaatct ggtatggtga ttttgtaggt
     7261 aatgtttgta tatgtcaaat acagttttta aggaaaggaa gaacatctta gggtaaacag
     7321 cagctagaaa ggtgaggggc aggagagtgg tgcatccttg ctgctgccag cagtgcccag
     7381 ataccaggct ttggggaatg agtggatggc tggaccattt gctaagacag aggccagggg
     7441 atgggagaaa tgatgagttt tggaaagatt cgatgtgact agactgaata taggcagttg
     7501 gatactagac tttggaattt aaaaagaatg tctggagtta gaattgagag acttgaacgt
     7561 ggagatggag gtcaggctgc agtgcgatgg gatcatctat ggagcatatg aggagaagag
     7621 aatctggagg aggaggaggg ggagccagca ggggagcagc tgtgggttgg aggaagccag
     7681 gagggagagt gcaatgccga gaaagcaatg aagagcgttt cgaagcatgc cagcagaacc
     7741 caatgctgca aagaggcctg ggaatgggat tgctgagggc ccttctcaca gtgagcccct
     7801 caagagcagc gtcaggggat tgtggggact gttggcacac agctggcttt gctaggttga
     7861 agacaatggg aggtgtggaa gacttgttga ctcatttaaa gaagattgga gggaaaggta
     7921 ggattgagag tgtttcagac agaaaaagga ttatatgctg agggtaaagc acaagtacag
     7981 agggttgcag atagtgcaga agtctttaaa aacaattatt ttaacccaac ttccagggag
     8041 actgaatttc ttctgccagt cagtaacacc atcaacctgg gagttgcccc tgacccctcc
     8101 agtcttagct cctgctcctg taacaaaata ccacaaactg gttagcttat agagaacaga
     8161 tgtttatttc ttacagttca ggagtctgga agtccaagat catggtgcca tcatggccga
     8221 gttctggtga gggccctctt ctgggatgca gcggccagct tctcatgttc tcacagtggg
     8281 tggagggtaa gcttgctctc tggcctcctc ttaaaaaggc actaatccca ttcatgaggg
     8341 ctccaccttc atgacctaat tacctcccaa agatgccatc tccaaacacc atcattctgg
     8401 ggattccatt tcaacatgat ttgggggata catcagacca taacactttt ctttttctca
     8461 accttcacat ccagttggtt ctcaagccct ggcgatttta cgcgctagat aggtcttaag
     8521 ttcatctcta cgcctgccct ggttaaggtt ctcatcattt ctcctctgga ttcatctgca
     8581 acacaggctg ccgggttggt tcccacctcc tagagctgga agagtgggct ctctgattct
     8641 ttacaccccc gcctcaatcc tcctgctgcc tgaataacca tctccccgtg acctaggata
     8701 tatcccagcc ccttagaggc atgcaaagcc ttccatgtct gaccctgcct catgtcttgg
     8761 aagccctaga ctgctgctgt accctgaagg aggtacctgc tcacattggc ccctctgtct
     8821 ggaataaccc caccccggtt ccacccaagt caggaaagct tcccaacccc tccctcccac
     8881 caccccaaag ctaagtgaag tgacccctct tcttgcctct gtaacaccgc catgcacatt
     8941 tcatacagcc cttgctgaaa cttcatctag ttctctgtta gacttaacat tccctaaggg
     9001 caggtttgga accttactca tctttatatg gcgtctaaaa tagtgcttgc tttatgatag
     9061 gtgctcagta aaggttgtct tgaattgagc agatcctcta gggacaggag ttggatggag
     9121 agcagactgt aaagcctcat gagggcaggg gccctgcctc ttcctgagct caggataccc
     9181 agagcctagc tcagtgcctg ccatgaaatt gttcactcca tcaagccttg ttaaatgagt
     9241 tcggggcggg gggagcatga tggttttctc tctctcagaa agaaagcgct gtatcaaagc
     9301 cctagcaccc tctctacacc caccttcagt atttcatatt agatgcggcc caagtgatac
     9361 tttctttacc gtcccgtgaa gacagcatat tggcagccct gcaaaaacaa aacaaaacaa
     9421 aaccctcagt tcatggcata cttgctataa atcagctatg tgtattgtca aattgtagaa
     9481 ctgaaagtat attctgattc ggtgtgtgta taaggaaata tacaccagta tatgcattaa
     9541 aacgtcaaga agagctgggc acagtgtcac atgcctgtaa acccagctat tcaggaggct
     9601 gaggtgggag gatcggttga ggccaggagt ttgaggctgc agtgagctat gattgcacag
     9661 ctgcactcca gcctgtgctg agacctcatc tcttaaaaaa taaaaaataa aaagtctaag
     9721 aggatacaca gaaattttta agtggttacc tccacggaat gggattaggg gatcagaggt
     9781 gagggaactc atggtttggc tatttctcgt tctttctgca ctgtttcaaa tttttacaag
     9841 tgtatgttat tgtactttta aaaagattag cttggcaaca agtctagcct gaaatgggtg
     9901 ctattttgac tagtctgagt gaaaagtgag gatttaaatg aagtaacccc taaactcagc
     9961 cagtcccatg tttttttaac acttggaata tctaattcca tttacactgc attcttcaaa
    10021 tgtaattttc aaagatgcct tttgcctcat cccttgcttt taagtattat tatagacttt
    10081 tggagactca cgaaacaagc aatccctaaa ttctcgccca ggaaagtatc ttggattaaa
    10141 tggtttttga gaaccttgag agtgtatatt ctatgaaatg gaagaaacaa gaactagaca
    10201 gagtcacaaa tgctgttgat cacagacaat ctctgccatc cataaggtaa atgtaataca
    10261 tctggcgacc tgctgagtgt gaacttgcag caggtgagga aggaactctg aactctcaca
    10321 atcttgtttc ttcatttccc agagagaaac tcggcaaaga gaaaaaggac atttccctcc
    10381 aggttatctg aaagaatttc aatgcttacc tttaatcatg tgacattgtt tatcttggat
    10441 taaaagaaaa gaaaatgtat ttattttgtg catattttca ataaaatata taaaatcgag
    10501 ttggtatata gtgccaaata ccattaatta aaaatatttt aacctga
//
