LOCUS       NM_006208               7438 bp    mRNA    linear   PRI 06-OCT-2024
DEFINITION  Homo sapiens ectonucleotide pyrophosphatase/phosphodiesterase 1
            (ENPP1), mRNA.
ACCESSION   NM_006208
VERSION     NM_006208.3
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 7438)
  AUTHORS   Ansh,A.J., Stabach,P.R., Ciccone,C., Cao,W., De La Cruz,E.M.,
            Sabbagh,Y., Carpenter,T.O., Ferreira,C.R. and Braddock,D.T.
  TITLE     Quantitative correlation of ENPP1 pathogenic variants with disease
            phenotype
  JOURNAL   Bone 186, 117136 (2024)
   PUBMED   38806089
  REMARK    GeneRIF: Quantitative correlation of ENPP1 pathogenic variants with
            disease phenotype.
REFERENCE   2  (bases 1 to 7438)
  AUTHORS   Sun,F., Yang,Y., Jia,L., Dong,Q.Q., Hu,W., Tao,H., Lu,C. and
            Yang,J.J.
  TITLE     TET3 boosts hepatocyte autophagy and impairs non-alcoholic fatty
            liver disease by increasing ENPP1 promoter hypomethylation
  JOURNAL   Free Radic Biol Med 218, 166-177 (2024)
   PUBMED   38582229
  REMARK    GeneRIF: TET3 boosts hepatocyte autophagy and impairs non-alcoholic
            fatty liver disease by increasing ENPP1 promoter hypomethylation.
REFERENCE   3  (bases 1 to 7438)
  AUTHORS   An,Y., Zhu,J., Xie,Q., Feng,J., Gong,Y., Fan,Q., Cao,J., Huang,Z.,
            Shi,W., Lin,Q., Wu,L., Yang,C. and Ji,T.
  TITLE     Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING
            Signaling
  JOURNAL   Adv Sci (Weinh) 11 (20), e2308131 (2024)
   PUBMED   38498770
  REMARK    GeneRIF: Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit
            cGAS-STING Signaling.
REFERENCE   4  (bases 1 to 7438)
  AUTHORS   Ma,X., Li,Y., Zhu,H., Lu,K., Huang,Y., Li,X., Han,S., Ding,H. and
            Sun,S.
  TITLE     ENPP1 inhibits the transcription activity of the hepatitis B virus
            pregenomic promoter by upregulating the acetylation of LMNB1
  JOURNAL   Arch Virol 169 (2), 36 (2024)
   PUBMED   38265511
  REMARK    GeneRIF: ENPP1 inhibits the transcription activity of the hepatitis
            B virus pregenomic promoter by upregulating the acetylation of
            LMNB1.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 7438)
  AUTHORS   Belli,S.I., Mercuri,F.A., Sali,A. and Goding,J.W.
  TITLE     Autophosphorylation of PC-1 (alkaline phosphodiesterase
            I/nucleotide pyrophosphatase) and analysis of the active site
  JOURNAL   Eur J Biochem 228 (3), 669-676 (1995)
   PUBMED   7737162
REFERENCE   6  (bases 1 to 7438)
  AUTHORS   Maddux,B.A., Sbraccia,P., Kumakura,S., Sasson,S., Youngren,J.,
            Fisher,A., Spencer,S., Grupe,A., Henzel,W., Stewart,T.A. et al.
  TITLE     Membrane glycoprotein PC-1 and insulin resistance in
            non-insulin-dependent diabetes mellitus
  JOURNAL   Nature 373 (6513), 448-451 (1995)
   PUBMED   7830796
REFERENCE   7  (bases 1 to 7438)
  AUTHORS   Belli,S.I. and Goding,J.W.
  TITLE     Biochemical characterization of human PC-1, an enzyme possessing
            alkaline phosphodiesterase I and nucleotide pyrophosphatase
            activities
  JOURNAL   Eur J Biochem 226 (2), 433-443 (1994)
   PUBMED   8001561
REFERENCE   8  (bases 1 to 7438)
  AUTHORS   Ziegler,S.G., Gahl,W.A. and Ferreira,C.R.
  TITLE     Generalized Arterial Calcification of Infancy
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   25392903
REFERENCE   9  (bases 1 to 7438)
  AUTHORS   Funakoshi,I., Kato,H., Horie,K., Yano,T., Hori,Y., Kobayashi,H.,
            Inoue,T., Suzuki,H., Fukui,S., Tsukahara,M. et al.
  TITLE     Molecular cloning of cDNAs for human fibroblast nucleotide
            pyrophosphatase
  JOURNAL   Arch Biochem Biophys 295 (1), 180-187 (1992)
   PUBMED   1315502
REFERENCE   10 (bases 1 to 7438)
  AUTHORS   Buckley,M.F., Loveland,K.A., McKinstry,W.J., Garson,O.M. and
            Goding,J.W.
  TITLE     Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human
            molecule, amino acid sequence, and chromosomal location
  JOURNAL   J Biol Chem 265 (29), 17506-17511 (1990)
   PUBMED   2211644
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL139805.15 and AL117378.15.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Oct 3, 2018 this sequence version replaced NM_006208.2.
            
            Summary: This gene is a member of the ecto-nucleotide
            pyrophosphatase/phosphodiesterase (ENPP) family. The encoded
            protein is a type II transmembrane glycoprotein comprising two
            identical disulfide-bonded subunits. This protein has broad
            specificity and cleaves a variety of substrates, including
            phosphodiester bonds of nucleotides and nucleotide sugars and
            pyrophosphate bonds of nucleotides and nucleotide sugars. This
            protein may function to hydrolyze nucleoside 5' triphosphates to
            their corresponding monophosphates and may also hydrolyze
            diadenosine polyphosphates. Mutations in this gene have been
            associated with 'idiopathic' infantile arterial calcification,
            ossification of the posterior longitudinal ligament of the spine
            (OPLL), and insulin resistance. [provided by RefSeq, Jul 2008].
            
            Sequence Note: The translation start codon selected for this RefSeq
            is conserved in several species. A possible downstream start codon
            would reduce the protein length by 52 aa, and this start codon is
            referred to in PMID:2211644. No experimental evidence exists
            regarding which start codon is used. This RefSeq record was created
            from genomic sequence to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on 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 :: M57736.1, BC059375.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000647893.1/ ENSP00000498074.1
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-256               AL139805.15        14633-14888
            257-329             AL117378.15        20487-20559
            330-446             AL117378.15        22701-22817
            447-572             AL117378.15        23853-23978
            573-633             AL117378.15        24886-24946
            634-731             AL117378.15        27637-27734
            732-811             AL117378.15        31379-31458
            812-931             AL117378.15        33098-33217
            932-1041            AL117378.15        34306-34415
            1042-1107           AL117378.15        37217-37282
            1108-1180           AL117378.15        37577-37649
            1181-1289           AL117378.15        40729-40837
            1290-1421           AL117378.15        42069-42200
            1422-1453           AL117378.15        44781-44812
            1454-1581           AL117378.15        45634-45761
            1582-1651           AL117378.15        46979-47048
            1652-1739           AL117378.15        48487-48574
            1740-1909           AL117378.15        49703-49872
            1910-1961           AL117378.15        51253-51304
            1962-2116           AL117378.15        52591-52745
            2117-2246           AL117378.15        55056-55185
            2247-2327           AL117378.15        56405-56485
            2328-2460           AL117378.15        57642-57774
            2461-2623           AL117378.15        59273-59435
            2624-7438           AL117378.15        63052-67866
FEATURES             Location/Qualifiers
     source          1..7438
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q23.2"
     gene            1..7438
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /note="ectonucleotide pyrophosphatase/phosphodiesterase 1"
                     /db_xref="GeneID:5167"
                     /db_xref="HGNC:HGNC:3356"
                     /db_xref="MIM:173335"
     exon            1..256
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     CDS             17..2794
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /EC_number="3.1.4.1"
                     /EC_number="3.6.1.9"
                     /note="plasma-cell membrane glycoprotein 1;
                     phosphodiesterase I/nucleotide pyrophosphatase 1; alkaline
                     phosphodiesterase 1; membrane component, chromosome 6,
                     surface marker 1; Ly-41 antigen; E-NPP 1; plasma-cell
                     membrane glycoprotein PC-1; NPPase; nucleotide
                     diphosphatase; alkaline phosphodiesterase I"
                     /codon_start=1
                     /product="ectonucleotide pyrophosphatase/phosphodiesterase
                     family member 1"
                     /protein_id="NP_006199.2"
                     /db_xref="CCDS:CCDS5150.2"
                     /db_xref="GeneID:5167"
                     /db_xref="HGNC:HGNC:3356"
                     /db_xref="MIM:173335"
                     /translation="MERDGCAGGGSRGGEGGRAPREGPAGNGRDRGRSHAAEAPGDPQ
                     AAASLLAPMDVGEEPLEKAARARTAKDPNTYKVLSLVLSVCVLTTILGCIFGLKPSCA
                     KEVKSCKGRCFERTFGNCRCDAACVELGNCCLDYQETCIEPEHIWTCNKFRCGEKRLT
                     RSLCACSDDCKDKGDCCINYSSVCQGEKSWVEEPCESINEPQCPAGFETPPTLLFSLD
                     GFRAEYLHTWGGLLPVISKLKKCGTYTKNMRPVYPTKTFPNHYSIVTGLYPESHGIID
                     NKMYDPKMNASFSLKSKEKFNPEWYKGEPIWVTAKYQGLKSGTFFWPGSDVEINGIFP
                     DIYKMYNGSVPFEERILAVLQWLQLPKDERPHFYTLYLEEPDSSGHSYGPVSSEVIKA
                     LQRVDGMVGMLMDGLKELNLHRCLNLILISDHGMEQGSCKKYIYLNKYLGDVKNIKVI
                     YGPAARLRPSDVPDKYYSFNYEGIARNLSCREPNQHFKPYLKHFLPKRLHFAKSDRIE
                     PLTFYLDPQWQLALNPSERKYCGSGFHGSDNVFSNMQALFVGYGPGFKHGIEADTFEN
                     IEVYNLMCDLLNLTPAPNNGTHGSLNHLLKNPVYTPKHPKEVHPLVQCPFTRNPRDNL
                     GCSCNPSILPIEDFQTQFNLTVAEEKIIKHETLPYGRPRVLQKENTICLLSQHQFMSG
                     YSQDILMPLWTSYTVDRNDSFSTEDFSNCLYQDFRIPLSPVHKCSFYKNNTKVSYGFL
                     SPPQLNKNSSGIYSEALLTTNIVPMYQSFQVIWRYFHDTLLRKYAEERNGVNVVSGPV
                     FDFDYDGRCDSLENLRQKRRVIRNQEILIPTHFFIVLTSCKDTSQTPLHCENLDTLAF
                     ILPHRTDNSESCVHGKHDSSWVEELLMLHRARITDVEHITGLSFYQQRKEPVSDILKL
                     KTHLPTFSQED"
     exon            257..329
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            330..446
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            447..572
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            573..633
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            634..731
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            732..811
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            812..931
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            932..1041
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1042..1107
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1108..1180
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1181..1289
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1290..1421
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1422..1453
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1454..1581
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1582..1651
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1652..1739
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1740..1909
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1910..1961
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1962..2116
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2117..2246
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2247..2327
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2328..2460
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2461..2623
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2624..7438
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3033..3038
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /note="hexamer: AATAAA"
     polyA_site      3056
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /note="major polyA site"
     regulatory      3451..3456
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /note="hexamer: AATATA"
     polyA_site      3472
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
     regulatory      6174..6179
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /note="hexamer: AATAAA"
     polyA_site      6200
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
     regulatory      7419..7424
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /note="hexamer: AATAAA"
     polyA_site      7438
                     /gene="ENPP1"
                     /gene_synonym="ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1;
                     PDNP1"
                     /note="major polyA site"
ORIGIN      
        1 agcggccggg gccacgatgg agcgcgacgg ctgcgcgggg ggcgggagcc gcggcggcga
       61 gggcgggcgc gctccccggg agggcccggc ggggaacggc cgcgatcggg gccgcagcca
      121 cgctgccgag gcgcccgggg acccgcaggc ggccgcgtcc ttgctggccc ctatggacgt
      181 gggggaggag ccgctggaga aggcggcgcg cgcccgcact gccaaggacc ccaacaccta
      241 taaagtactc tcgctggtat tgtcagtatg tgtgttaaca acaatacttg gttgtatatt
      301 tgggttgaaa ccaagctgtg ccaaagaagt taaaagttgc aaaggtcgct gtttcgagag
      361 aacatttggg aactgtcgct gtgatgctgc ctgtgttgag cttggaaact gctgtttaga
      421 ttaccaggag acgtgcatag aaccagaaca tatatggact tgcaacaaat tcaggtgtgg
      481 tgagaaaagg ttgaccagaa gcctctgtgc ctgttcagat gactgcaagg acaagggcga
      541 ctgctgcatc aactacagtt ctgtgtgtca aggtgagaaa agttgggtag aagaaccatg
      601 tgagagcatt aatgagccac agtgcccagc agggtttgaa acgcctccta ccctcttatt
      661 ttctttggat ggattcaggg cagaatattt acacacttgg ggtggacttc ttcctgttat
      721 tagcaaacta aaaaaatgtg gaacatatac taaaaacatg agaccggtat atccaacaaa
      781 aactttcccc aatcactaca gcattgtcac cggattgtat ccagaatctc atggcataat
      841 cgacaataaa atgtatgatc ccaaaatgaa tgcttccttt tcacttaaaa gtaaagagaa
      901 atttaatcct gagtggtaca aaggagaacc aatttgggtc acagctaagt atcaaggcct
      961 caagtctggc acatttttct ggccaggatc agatgtggaa attaacggaa ttttcccaga
     1021 catctataaa atgtataatg gttcagtacc atttgaagaa aggattttag ctgttcttca
     1081 gtggctacag cttcctaaag atgaaagacc acacttttac actctgtatt tagaagaacc
     1141 agattcttca ggtcattcat atggaccagt cagcagtgaa gtcatcaaag ccttgcagag
     1201 ggttgatggt atggttggta tgctgatgga tggtctgaaa gagctgaact tgcacagatg
     1261 cctgaacctc atccttattt cagatcatgg catggaacaa ggcagttgta agaaatacat
     1321 atatctgaat aaatatttgg gggatgttaa aaatattaaa gttatctatg gacctgcagc
     1381 tcgattgaga ccctctgatg tcccagataa atactattca tttaactatg aaggcattgc
     1441 ccgaaatctt tcttgccggg aaccaaacca gcacttcaaa ccttacctga aacatttctt
     1501 acctaagcgt ttgcactttg ctaagagtga tagaattgag cccttgacat tctatttgga
     1561 ccctcagtgg caacttgcat tgaatccctc agaaaggaaa tattgtggaa gtggatttca
     1621 tggctctgac aatgtatttt caaatatgca agccctcttt gttggctatg gacctggatt
     1681 caagcatggc attgaggctg acacctttga aaacattgaa gtctataact taatgtgtga
     1741 tttactgaat ttgacaccgg ctcctaataa cggaactcat ggaagtctta accaccttct
     1801 aaagaatcct gtttatacgc caaagcatcc caaagaagtg caccccctgg tacagtgccc
     1861 cttcacaaga aaccccagag ataaccttgg ctgctcatgt aacccttcga ttttgccgat
     1921 tgaggatttt caaacacagt tcaatctgac tgtggcagaa gagaagatta ttaagcatga
     1981 aactttaccc tatggaagac ctagagttct ccagaaggaa aacaccatct gtcttctttc
     2041 ccagcaccag tttatgagtg gatacagcca agacatctta atgccccttt ggacatccta
     2101 taccgtggac agaaatgaca gtttctctac ggaagacttc tccaactgtc tgtaccagga
     2161 ctttagaatt cctcttagtc ctgtccataa atgttcattt tataaaaata acaccaaagt
     2221 gagttacggg ttcctctccc caccacaact aaataaaaat tcaagtggaa tatattctga
     2281 agctttgctt actacaaata tagtgccaat gtaccagagt tttcaagtta tatggcgcta
     2341 ctttcatgac accctactgc gaaagtatgc tgaagaaaga aatggtgtca atgtcgtcag
     2401 tggtcctgtg tttgactttg attatgatgg acgttgtgat tccttagaga atctgaggca
     2461 aaaaagaaga gtcatccgta accaagaaat tttgattcca actcacttct ttattgtgct
     2521 aacaagctgt aaagatacat ctcagacgcc tttgcactgt gaaaacctag acaccttagc
     2581 tttcattttg cctcacagga ctgataacag cgagagctgt gtgcatggga agcatgactc
     2641 ctcatgggtt gaagaattgt taatgttaca cagagcacgg atcacagatg ttgagcacat
     2701 cactggactc agcttctatc aacaaagaaa agagccagtt tcagacattt taaagttgaa
     2761 aacacatttg ccaaccttta gccaagaaga ctgatatgtt ttttatcccc aaacaccatg
     2821 aatctttttg agagaacctt atattttata tagtcctcta gctacactat tgcattgttc
     2881 agaaactgtc gaccagagtt agaacggagc cctcggtgat gcggacatct cagggaaact
     2941 tgcgtactca gcacagcagt ggagagtgtt cctgttgaat cttgcacata tttgaatgtg
     3001 taagcattgt atacattgat caagttcggg ggaataaaga cagaccacac ctaaaactgc
     3061 ctttctgctt ctcttaaagg agaagtagct gtgaacattg tctggatacc agatatttga
     3121 atctttctta ctattggtaa taaaccttga tggcattggg caaacagtag acttatagta
     3181 gggttggggt agcccatgtt atgtgactat ctttatgaga attttaaagt ggttctggat
     3241 atcttttaac ttggagtttc atttcttttc attgtaatca aaaaaaaaat taacagaagc
     3301 caaaatactt ctgagacctt gtttcaatct ttgctgtata tcccctcaaa atccaagtta
     3361 ttaatcttat gtgttttctt tttaattttt tgattggatt tctttagatt taatggttca
     3421 aatgagttca actttgaggg acgatctttg aatatactta cctattataa aatcttactt
     3481 tgtatttgta tttaaaaaag aaaaatattc ctatcctgct cactggtaat taacataggt
     3541 ttaaaatggc ttcaaatgtg gccctataga cggttaaaat tgtaccttat cttggcaaaa
     3601 cttcagagca ccagtcagtg catgcaaggt gccatttttt attgagatgc ttagaatgtt
     3661 tctttctgtg cacaagactt accctaccag cagcagagcc attctctgtt gagtggttca
     3721 ttttgaagtt ccacagattg aagagaacat gccaccaatc acctcacatc ttcttggtgg
     3781 acatgataaa tgacacaatg aacttgattt ctttactacc ttgactgtag ctttttatcc
     3841 ctacctgtga accttcaaag actgcattaa cttttaggct acataggtcc aattgaggta
     3901 taatatcagt acaccaaaga tttttatatg tccttcgtgt gaccattctt caacggccta
     3961 agggccagct gcaaagactt ttggaaaata caatttacaa ctcaaaatta tttaataatt
     4021 taggaagttg cttttttttt tttttttttt cagtcctgca gtttcctgaa gctctgtata
     4081 tgatattttt ttcagcctgc ttctctctgt tgttcagatt aggtaatttt attcttctgt
     4141 ctcgaagctc actgattctt tattctgtct aatctgttct gctgttgagc ccatttattc
     4201 ctgattttta tattttagtt attgtatgtt ttatttctaa aatttccatt cagtttttct
     4261 ttatatcttc tatttgctga gaatttctgt ctctttgctg agactttcta cgttttcatt
     4321 tgtttcaagt gcatttatac ttgcttgttg aagaattttt atgatggctg ctgtaaaatc
     4381 cttatcagat aattccaaca tctgtcacct cattgtttgc atctactgat ggtctttttt
     4441 ccattcggaa acattttcct gtttcttggt gtgtggaatg attttttatt gaaacctgga
     4501 tatttttagg tattatgtta tgagactatg ggtcttattt aaaccttctg ctttagccaa
     4561 ctttctcaga taccaccaca gcaggggaat tgggagcact gcttcattat taccaggtgt
     4621 ggctaggagt ccaggttccc cagtcagcct ccctttatac tgagtaacag ggtcccctca
     4681 ttactactgg gcaaggtgag aattcagttt cccattaggt ctttattgat tcttccctgg
     4741 ctggaatgtg cagcggcacc ttttggtgca ccctgggaat ctccactaat gctatgggac
     4801 agagtgacca ggaagagctt cattacacca ggtgggaatg aaattcccag tagcctacac
     4861 agccttctcc gacaccactc tggagttgta ttcttccagc acacaaacat acacaattta
     4921 actcaaagca tcttagcaga gcttaattaa atggatagat gcctgttccc tttgctggat
     4981 accaagaata caaaagtcag ggagttgggg cacctcttta cagcttggtg agagtgtaag
     5041 tctggactcc ccactcagca tttgctggta tgggtggggc catggtgttt ttccatggtg
     5101 tttggttgga gtacagcctt ttttaccctt gcttggctac ccttttctgg tcctttggca
     5161 ggagagagca ggactctctt agggcttttt tttcccctgc atttattgac atttccaggt
     5221 tgctgacttt ttcagctcca agttggaaat atatgagctg aaaagaaaat gtagggaact
     5281 catcacagtg ttgttacttg ggccccaatg ttcctagcct attttctgtc tactattcag
     5341 agtcttgctg tgttttaata taatatccag gatttttata tgcatttagc agaaggatgt
     5401 ctactctgcc tttgtagaag tgtctcactg atttttacat atttttccag cacacaaaca
     5461 tacacaattt aactcaaagc atcttagcag agcttaatta aatggataga tgtctgttcc
     5521 ctttgctgga cgccaagaat acaaaaaaga acaagtgaca attttctctg tcttagggag
     5581 aagagacagc agaagtgtaa atgatcccta aagagtgata gatgttatca tgaagccaca
     5641 ggaggggtgc caggctgcac aaaagagaca ctggatgctt cttggtagta gaggcagtgg
     5701 cttcccagcc ttggggctaa ggcttgtagg gtgaattgga acttttcaga tgagcaaggc
     5761 aaagaaggga ccttctaaca ttccttggat ggaacatttt tgacattttc ccatttacag
     5821 ctacttatat tttctacaag tgtcactgtg accaacttat gtacacatac tttttcttgc
     5881 ttagttataa taatctgttc ttaaagaaaa tgtcagtctc tacattctat gctgactgtt
     5941 aaggaaagag cacccacatc tgctcctact tagctttttt tctgtggttc ttacacagta
     6001 ttcctttttt tcttttcttg aaagagactc ctcctttctt ttcttttctt gaaagagttt
     6061 taaacagata agatggcaaa agtgactgat ctctactccc ccagtttgaa tggtaaattt
     6121 gaatggtaaa ttcccatgaa catatatgga aatgtcttta tcctactttc tccaataaag
     6181 gctgttctta gcttttcaaa tgcaaagtga aacctttatt tatcttgatt tctttttttt
     6241 tttttttttt tttttttttt ttgagatgct ctgtcaccca ggctggagtg cagtggcaag
     6301 atcttggctc actgcaagct ccgcctccca ggttcacgcc attctcctgg ctcagcctcc
     6361 cgagtaactg ggactacagg cacctgccgt cacgcctggc taattttttg tatttttagt
     6421 agagaatgga gtttcaccgt gttagccagg atggtctcga tctcctgacc ttgtgatctg
     6481 cccgcctcgg cctcccaaag tgctgggatt acaggctcga gccactgcct ccagcctatc
     6541 ctgatttcta ctgtcatgcc tcacatcagt cctttttttt ttttttgaga cagagtctcg
     6601 ctctgtggcc caggctagac tgcagtggca tgatctcggc tcactgcaac ctccacctcc
     6661 ggggttctag caattctcct gcctcagcct cctgagtagc tgggattata ggcgcatgcc
     6721 acacctggct ttttgtattt tagtggagat ggggtttcac tgtgttgctc aggctggtct
     6781 tgatctcctg agctcagaca atccccccgc cttggcctcc caaagtgcta ggattatagg
     6841 cgagagctgc tgtgtgcttc ttaagtgagg taagtaactt ccatagaaaa tttccatcag
     6901 ttcattcatg aaagaacaaa gaacctggca aaacttaaaa aaacgtttcc aagaatcaga
     6961 taaaagagga caaaccttag ggagaagaag gcagctgctc atttccagca ggggaagtag
     7021 ctgcatagag tacaaggact ggtaggcctg ttggctgttc ctgtttaagg agacaagatg
     7081 ggcatggaac agggaccacc ccctcctctg ggagaagctg ttaccccctt cacttttcct
     7141 cctctgtcat tacccacaat cactctcctt ctttgcgcta tggtaggtgt ttacccatca
     7201 taggaatggg catttgaact ttgaaactga atgtggtgat tacacttcat gctgaagctt
     7261 ttcacatgag tgctttcata agcattaagt aaaattttat aatgactgca gtccaaggac
     7321 attttccctg gtttttggcc agtctaaata ttgtaagaga gagagaagaa aagtgtacgg
     7381 aatataattg tctctaagct aagaaatgtg gatgttcaaa taaaacatac gtacagaa
//
