LOCUS       NM_020318               9683 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens pappalysin 2 (PAPPA2), transcript variant 1, mRNA.
ACCESSION   NM_020318
VERSION     NM_020318.3
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 9683)
  AUTHORS   Upners,E.N., Ljubicic,M.L., Busch,A.S., Fischer,M.B., Almstrup,K.,
            Petersen,J.H., Jensen,R.B., Hagen,C.P. and Juul,A.
  TITLE     Dynamic Changes in Serum IGF-I and Growth During Infancy:
            Associations to Body Fat, Target Height, and PAPPA2 Genotype
  JOURNAL   J Clin Endocrinol Metab 107 (1), 219-229 (2022)
   PUBMED   34476481
  REMARK    GeneRIF: Dynamic Changes in Serum IGF-I and Growth During Infancy:
            Associations to Body Fat, Target Height, and PAPPA2 Genotype.
REFERENCE   2  (bases 1 to 9683)
  AUTHORS   Babiker,A., Al Noaim,K., Al Swaid,A., Alfadhel,M., Deeb,A.,
            Martin-Rivada,A., Barrios,V., Perez-Jurado,L.A., Alfares,A., Al
            Alwan,I. and Argente,J.
  TITLE     Short stature with low insulin-like growth factor 1 availability
            due to pregnancy-associated plasma protein A2 deficiency in a Saudi
            family
  JOURNAL   Clin Genet 100 (5), 601-606 (2021)
   PUBMED   34272725
  REMARK    GeneRIF: Short stature with low insulin-like growth factor 1
            availability due to pregnancy-associated plasma protein A2
            deficiency in a Saudi family.
REFERENCE   3  (bases 1 to 9683)
  AUTHORS   Wang,Y., Jia,H., Gao,W.H., Zou,T., Yao,S., Du,M.F., Zhang,X.Y.,
            Chu,C., Liao,Y.Y., Chen,C., Wang,D., Ma,Q., Hu,J.W., Wang,K.K.,
            Yan,Y., Sun,Y., Hu,G.L., Niu,Z.J., Zhou,H.W., Zhang,X., Wang,X.,
            Li,C.H., Chen,F.Y., Gao,K., Zhang,J., Guan,Y.J., Chang,J.,
            Yang,T.L. and Mu,J.J.
  TITLE     Associations of plasma PAPP-A2 and genetic variations with salt
            sensitivity, blood pressure changes and hypertension incidence in
            Chinese adults
  JOURNAL   J Hypertens 39 (9), 1817-1825 (2021)
   PUBMED   33783375
  REMARK    GeneRIF: Associations of plasma PAPP-A2 and genetic variations with
            salt sensitivity, blood pressure changes and hypertension incidence
            in Chinese adults.
REFERENCE   4  (bases 1 to 9683)
  AUTHORS   Keikkala,E., Forsten,J., Ritvos,O., Stenman,U.H., Kajantie,E.,
            Hamalainen,E., Raikkonen,K., Villa,P.M. and Laivuori,H.
  TITLE     Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia
            during the first and second trimesters in high-risk women
  JOURNAL   Pregnancy Hypertens 25, 116-122 (2021)
   PUBMED   34116346
  REMARK    GeneRIF: Serum Inhibin-A and PAPP-A2 in the prediction of
            pre-eclampsia during the first and second trimesters in high-risk
            women.
REFERENCE   5  (bases 1 to 9683)
  AUTHORS   Harsanyi,S., Zamborsky,R., Krajciova,L., Kokavec,M. and
            Danisovic,L.
  TITLE     Genetic Study of IL6, GDF5 and PAPPA2 in Association with
            Developmental Dysplasia of the Hip
  JOURNAL   Genes (Basel) 12 (7), 986 (2021)
   PUBMED   34203285
  REMARK    GeneRIF: Genetic Study of IL6, GDF5 and PAPPA2 in Association with
            Developmental Dysplasia of the Hip.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 9683)
  AUTHORS   Boldt,H.B., Overgaard,M.T., Laursen,L.S., Weyer,K.,
            Sottrup-Jensen,L. and Oxvig,C.
  TITLE     Mutational analysis of the proteolytic domain of
            pregnancy-associated plasma protein-A (PAPP-A): classification as a
            metzincin
  JOURNAL   Biochem J 358 (Pt 2), 359-367 (2001)
   PUBMED   11513734
REFERENCE   7  (bases 1 to 9683)
  AUTHORS   Page,N.M., Butlin,D.J., Lomthaisong,K. and Lowry,P.J.
  TITLE     The characterization of pregnancy associated plasma protein-E and
            the identification of an alternative splice variant
  JOURNAL   Placenta 22 (8-9), 681-687 (2001)
   PUBMED   11597188
REFERENCE   8  (bases 1 to 9683)
  AUTHORS   Overgaard,M.T., Boldt,H.B., Laursen,L.S., Sottrup-Jensen,L.,
            Conover,C.A. and Oxvig,C.
  TITLE     Pregnancy-associated plasma protein-A2 (PAPP-A2), a novel
            insulin-like growth factor-binding protein-5 proteinase
  JOURNAL   J Biol Chem 276 (24), 21849-21853 (2001)
   PUBMED   11264294
REFERENCE   9  (bases 1 to 9683)
  AUTHORS   Farr,M., Strube,J., Geppert,H.G., Kocourek,A., Mahne,M. and
            Tschesche,H.
  TITLE     Pregnancy-associated plasma protein-E (PAPP-E)
  JOURNAL   Biochim Biophys Acta 1493 (3), 356-362 (2000)
   PUBMED   11018262
REFERENCE   10 (bases 1 to 9683)
  AUTHORS   Standker,L., Wobst,P., Mark,S. and Forssmann,W.G.
  TITLE     Isolation and characterization of circulating 13-kDa C-terminal
            fragments of human insulin-like growth factor binding protein-5
  JOURNAL   FEBS Lett 441 (2), 281-286 (1998)
   PUBMED   9883900
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC062665.1, AF342989.1,
            AF311940.1 and AL031290.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_020318.2.
            
            Summary: This gene encodes a member of the pappalysin family of
            metzincin metalloproteinases. The encoded protein cleaves
            insulin-like growth factor-binding protein 5 and is thought to be a
            local regulator of insulin-like growth factor (IGF)
            bioavailability. Alternative splicing results in multiple
            transcript variants. [provided by RefSeq, Jul 2010].
            
            Transcript Variant: This variant (1) encodes the longer 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.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF342989.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000367662.5/ ENSP00000356634.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-821               BC062665.1         9-829
            822-2499            AF342989.1         826-2503
            2500-6536           AF311940.1         1340-5376
            6537-6918           AF342989.1         6541-6922
            6919-9683           AL031290.1         63236-66000
FEATURES             Location/Qualifiers
     source          1..9683
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q25.2"
     gene            1..9683
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /note="pappalysin 2"
                     /db_xref="GeneID:60676"
                     /db_xref="HGNC:HGNC:14615"
                     /db_xref="MIM:619485"
     exon            1..244
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            245..2079
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     CDS             1161..6536
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; pregnancy-associated plasma preproprotein-A2;
                     placenta-specific 3; pregnancy-associated plasma protein
                     E1"
                     /codon_start=1
                     /product="pappalysin-2 isoform 1 precursor"
                     /protein_id="NP_064714.2"
                     /db_xref="CCDS:CCDS41438.1"
                     /db_xref="GeneID:60676"
                     /db_xref="HGNC:HGNC:14615"
                     /db_xref="MIM:619485"
                     /translation="MMCLKILRISLAILAGWALCSANSELGWTRKKSLVEREHLNQVL
                     LEGERCWLGAKVRRPRASPQHHLFGVYPSRAGNYLRPYPVGEQEIHHTGRSKPDTEGN
                     AVSLVPPDLTENPAGLRGAVEEPAAPWVGDSPIGQSELLGDDDAYLGNQRSKESLGEA
                     GIQKGSAMAATTTTAIFTTLNEPKPETQRRGWAKSRQRRQVWKRRAEDGQGDSGISSH
                     FQPWPKHSLKHRVKKSPPEESNQNGGEGSYREAETFNSQVGLPILYFSGRRERLLLRP
                     EVLAEIPREAFTVEAWVKPEGGQNNPAIIAGVFDNCSHTVSDKGWALGIRSGKDKGKR
                     DARFFFSLCTDRVKKATILISHSRYQPGTWTHVAATYDGRHMALYVDGTQVASSLDQS
                     GPLNSPFMASCRSLLLGGDSSEDGHYFRGHLGTLVFWSTALPQSHFQHSSQHSSGEEE
                     ATDLVLTASFEPVNTEWVPFRDEKYPRLEVLQGFEPEPEILSPLQPPLCGQTVCDNVE
                     LISQYNGYWPLRGEKVIRYQVVNICDDEGLNPIVSEEQIRLQHEALNEAFSRYNISWQ
                     LSVHQVHNSTLRHRVVLVNCEPSKIGNDHCDPECEHPLTGYDGGDCRLQGRCYSWNRR
                     DGLCHVECNNMLNDFDDGDCCDPQVADVRKTCFDPDSPKRAYMSVKELKEALQLNSTH
                     FLNIYFASSVREDLAGAATWPWDKDAVTHLGGIVLSPAYYGMPGHTDTMIHEVGHVLG
                     LYHVFKGVSERESCNDPCKETVPSMETGDLCADTAPTPKSELCREPEPTSDTCGFTRF
                     PGAPFTNYMSYTDDNCTDNFTPNQVARMHCYLDLVYQQWTESRKPTPIPIPPMVIGQT
                     NKSLTIHWLPPISGVVYDRASGSLCGACTEDGTFRQYVHTASSRRVCDSSGYWTPEEA
                     VGPPDVDQPCEPSLQAWSPEVHLYHMNMTVPCPTEGCSLELLFQHPVQADTLTLWVTS
                     FFMESSQVLFDTEILLENKESVHLGPLDTFCDIPLTIKLHVDGKVSGVKVYTFDERIE
                     IDAALLTSQPHSPLCSGCRPVRYQVLRDPPFASGLPVVVTHSHRKFTDVEVTPGQMYQ
                     YQVLAEAGGELGEASPPLNHIHGAPYCGDGKVSERLGEECDDGDLVSGDGCSKVCELE
                     EGFNCVGEPSLCYMYEGDGICEPFERKTSIVDCGIYTPKGYLDQWATRAYSSHEDKKK
                     CPVSLVTGEPHSLICTSYHPDLPNHRPLTGWFPCVASENETQDDRSEQPEGSLKKEDE
                     VWLKVCFNRPGEARAIFIFLTTDGLVPGEHQQPTVTLYLTDVRGSNHSLGTYGLSCQH
                     NPLIINVTHHQNVLFHHTTSVLLNFSSPRVGISAVALRTSSRIGLSAPSNCISEDEGQ
                     NHQGQSCIHRPCGKQDSCPSLLLDHADVVNCTSIGPGLMKCAITCQRGFALQASSGQY
                     IRPMQKEILLTCSSGHWDQNVSCLPVDCGVPDPSLVNYANFSCSEGTKFLKRCSISCV
                     PPAKLQGLSPWLTCLEDGLWSLPEVYCKLECDAPPIILNANLLLPHCLQDNHDVGTIC
                     KYECKPGYYVAESAEGKVRNKLLKIQCLEGGIWEQGSCIPVVCEPPPPVFEGMYECTN
                     GFSLDSQCVLNCNQEREKLPILCTKEGLWTQEFKLCENLQGECPPPPSELNSVEYKCE
                     QGYGIGAVCSPLCVIPPSDPVMLPENITADTLEHWMEPVKVQSIVCTGRRQWHPDPVL
                     VHCIQSCEPFQADGWCDTINNRAYCHYDGGDCCSSTLSSKKVIPFAADCDLDECTCRD
                     PKAEENQ"
     exon            2080..3151
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            3152..3297
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            3298..3591
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            3592..3784
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            3785..3906
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            3907..4396
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            4397..4525
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            4526..4617
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            4618..4811
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            4812..4958
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            4959..5094
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            5095..5311
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            5312..5483
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            5484..5661
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            5662..5875
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            5876..6044
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            6045..6180
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            6181..6290
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            6291..6362
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            6363..6461
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     exon            6462..9683
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /inference="alignment:Splign:2.1.0"
     regulatory      9660..9665
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /note="hexamer: ATTAAA"
     polyA_site      9683
                     /gene="PAPPA2"
                     /gene_synonym="PAPP-A2; PAPP-E; PAPPE; PLAC3; SSDA"
                     /note="major polyA site"
ORIGIN      
        1 atgactctct ctcttgagta ggcacacact cccttttctc gggtgtgtac tttttgcttt
       61 gtgatacatc tctgcacttt cagtattttc caactcatcc ttaaattcct tctcacaaca
      121 gtgtcaagag cctggacgcc agccaggatt gaggtcctac gggtgtttgg ggacctcccc
      181 aagcccacga gtatcaatgg cagtatcaat tgtctgtgac agtgattaag gagcaaaaca
      241 cttggaaccc acaagactcc cagaaggtga agttaagagc tcccagactc ataaggttat
      301 tagaacagca aactggcacc ccaaagaact ttacggagac ttgcaaccta tcaacaagtt
      361 ggatgaggga ttaaaagcct tcaacaacca acaaccccaa gcatcaaact gaaggaaaca
      421 ttctaacctt cacagacaga ctggaggctg gatggggacc tggctgaaga catctggaga
      481 atgaaagtta agtaccagct tgcatttttg tgcccctaga ttatttttgc attttaaaat
      541 aagaagcatc aaattgcgtg tctctgtgta aaagttctag caatttgttt taaggtgaac
      601 ttattttggc ttagggacta caaaaagaga aggtaattcc tagggaagga agaagagaaa
      661 gaaatgaaaa ttagagaata agattatttt gaatgacttc aggtagcgag gagtgtgtgt
      721 ttgtgagtgt gtatttgaga gacttggctc atgcctgtgg gtcttctctt ctagtatcag
      781 tgaggggagg gattactgaa gaagaagggg ggaaaaaaaa agaaagaaat ctgagctttc
      841 tgggaggaaa ttcaaaggaa ccaagagaaa ttaacttcgt tctgcaagga ctaaagtaca
      901 gcaagaggag agaggtcaag cgagaagcgt gcgggaagca catgccctgg ggaggcatag
      961 aagccacact ggcagagcgg ccagcacagg tagccagcag aggcattctt ggggctattt
     1021 gaaaaagttt ggtctgtgaa caaaacagtt tccctggtga ctgcaaatcc attgctagct
     1081 gcctctttct cgtctgccca tcactctggt gtggtaccca gaagttgact tctggttctg
     1141 tagaaagagc taggggaggt atgatgtgct taaagatcct aagaataagc ctggcgattt
     1201 tggctgggtg ggcactctgt tctgccaact ctgagctggg ctggacacgc aagaaatcct
     1261 tggttgagag ggaacacctg aatcaggtgc tgttggaagg agaacgttgt tggctggggg
     1321 ccaaggttcg aagacccaga gcttctccac agcatcacct ctttggagtc taccccagca
     1381 gggctgggaa ctacctaagg ccctaccccg tgggggagca agaaatccat catacaggac
     1441 gcagcaaacc agacactgaa ggaaatgctg tgagccttgt tcccccagac ctgactgaaa
     1501 atccagcagg actgaggggt gcagttgaag agccggctgc cccatgggta ggggatagtc
     1561 ctattgggca atctgagctg ctgggagatg atgacgctta tctcggcaat caaagatcca
     1621 aggagtctct aggtgaggcc gggattcaga aaggctcagc catggctgcc actactacca
     1681 ccgccatttt cacaaccctg aacgaaccca aaccagagac ccaaaggagg ggctgggcca
     1741 agtccaggca gcgtcgccaa gtgtggaaga ggcgggcgga agatgggcag ggagactccg
     1801 gtatctcttc acatttccaa ccttggccca agcattccct taaacacagg gtcaaaaaga
     1861 gtccaccgga ggaaagcaac caaaatggtg gagagggctc ctaccgagaa gcagagacct
     1921 ttaactccca agtaggactg cccatcttat acttctctgg gaggcgggag cggctgctgc
     1981 tgcgtccaga agtgctggct gagattcccc gggaggcgtt cacagtggaa gcctgggtta
     2041 aaccggaggg aggacagaac aacccagcca tcatcgcagg tgtgtttgat aactgctccc
     2101 acactgtcag tgacaaaggc tgggccctgg ggatccgctc agggaaggac aagggaaagc
     2161 gggatgctcg cttcttcttc tccctctgca ccgaccgcgt gaagaaagcc accatcttga
     2221 ttagccacag tcgctaccaa ccaggcacat ggacccatgt ggcagccact tacgatggac
     2281 ggcacatggc cctgtatgtg gatggcactc aggtggctag cagtctagac cagtctggtc
     2341 ccctgaacag ccccttcatg gcatcttgcc gctctttgct cctgggggga gacagctctg
     2401 aggatgggca ctatttccgt ggacacctgg gcacactggt tttctggtcg accgccctgc
     2461 cacaaagcca ttttcagcac agttctcagc attcaagtgg ggaggaggaa gcgactgact
     2521 tggtcctgac agcgagcttt gagcctgtga acacagagtg ggttcccttt agagatgaga
     2581 agtacccacg acttgaggtt ctccagggct ttgagccaga gcctgagatt ctgtcgcctt
     2641 tgcagccccc actctgtggg caaacagtct gtgacaatgt ggaattgatc tcccagtaca
     2701 atggatactg gccccttcgg ggagagaagg tgatacgcta ccaggtggtg aacatctgtg
     2761 atgatgaggg cctaaacccc attgtgagtg aggagcagat tcgtctgcag cacgaggcac
     2821 tgaatgaggc cttcagccgc tacaacatca gctggcagct gagcgtccac caggtccaca
     2881 attccaccct gcgacaccgg gttgtgcttg tgaactgtga gcccagcaag attggcaatg
     2941 accattgtga ccccgagtgt gagcacccac tcacaggcta tgatgggggt gactgccgcc
     3001 tgcagggccg ctgctactcc tggaaccgca gggatgggct ctgtcacgtg gagtgtaaca
     3061 acatgctgaa cgactttgac gacggagact gctgcgaccc ccaggtggct gatgtgcgca
     3121 agacctgctt tgaccctgac tcacccaaga gggcatacat gagtgtgaag gagctgaagg
     3181 aggccctgca gctgaacagt actcacttcc tcaacatcta ctttgccagc tcagtgcggg
     3241 aagaccttgc aggtgctgcc acctggcctt gggacaagga cgctgtcact cacctgggtg
     3301 gcattgtcct cagcccagca tattatggga tgcctggcca caccgacacc atgatccatg
     3361 aagtgggaca tgttctggga ctctaccatg tctttaaagg agtcagtgaa agagaatcct
     3421 gcaatgaccc ctgcaaggag acagtgccat ccatggaaac gggagacctc tgtgccgaca
     3481 ccgcccccac tcccaagagt gagctgtgcc gggaaccaga gcccactagt gacacctgtg
     3541 gcttcactcg cttcccaggg gctccgttca ccaactacat gagctacacg gatgataact
     3601 gcactgacaa cttcactcct aaccaagtgg cccgaatgca ttgctatttg gacctagtct
     3661 atcagcagtg gactgaaagc agaaagccca cccccatccc cattccacct atggtcatcg
     3721 gacagaccaa caagtccctc actatccact ggctgcctcc tattagtgga gttgtatatg
     3781 acagggcctc aggcagcttg tgtggcgctt gcactgaaga tgggaccttt cgtcagtatg
     3841 tgcacacagc ttcctcccgg cgggtgtgtg actcctcagg ttattggacc ccagaggagg
     3901 ctgtggggcc tcctgatgtg gatcagccct gcgagccaag cttacaggcc tggagccctg
     3961 aggtccacct gtaccacatg aacatgacgg tcccctgccc cacagaaggc tgtagcttgg
     4021 agctgctctt ccaacacccg gtccaagccg acaccctcac cctgtgggtc acttccttct
     4081 tcatggagtc ctcgcaggtc ctctttgaca cagagatctt gctggaaaac aaggagtcag
     4141 tgcacctggg ccccttagac actttctgtg acatcccact caccatcaaa ctgcacgtgg
     4201 atgggaaggt gtcgggggtg aaagtctaca cctttgatga gaggatagag attgatgcag
     4261 cactcctgac ttctcagccc cacagtccct tgtgctctgg ctgcaggcct gtgaggtacc
     4321 aggttctccg cgatccccca tttgccagtg gtttgcccgt ggtggtgaca cattctcaca
     4381 ggaagttcac ggacgtggag gtcacacctg gacagatgta tcagtaccaa gttctagctg
     4441 aagctggagg agaactggga gaagcttcgc ctcctctgaa ccacattcat ggagctcctt
     4501 attgtggaga tgggaaggtg tcagagagac tgggagaaga gtgtgatgat ggagaccttg
     4561 tgagcggaga tggctgctcc aaggtgtgtg agctggagga aggtttcaac tgtgtaggag
     4621 agccaagcct ttgctacatg tatgagggag atggcatatg tgaacctttt gagagaaaaa
     4681 ccagcattgt agactgtggc atctacactc ccaaaggata cttggatcaa tgggctaccc
     4741 gggcttactc ctctcatgaa gacaagaaga agtgtcctgt ttccttggta actggagaac
     4801 ctcattccct aatttgcaca tcataccatc cagatttacc caaccaccgt cccctaactg
     4861 gctggtttcc ctgtgttgcc agtgaaaatg aaactcagga tgacaggagt gaacagccag
     4921 aaggtagcct gaagaaagag gatgaggttt ggctcaaagt gtgtttcaat agaccaggag
     4981 aggccagagc aatttttatt tttttgacaa ctgatggcct agttcccgga gagcatcagc
     5041 agccgacagt gactctctac ctgaccgatg tccgtggaag caaccactct cttggaacct
     5101 atggactgtc atgccagcat aatccactga ttatcaatgt gacccatcac cagaatgtcc
     5161 ttttccacca taccacctca gtgctgctga atttctcatc cccacgggtc ggcatctcag
     5221 ctgtggctct aaggacatcc tcccgcattg gtctttcggc tcccagtaac tgcatctcag
     5281 aggacgaggg gcagaatcat cagggacaga gctgtatcca tcggccctgt gggaagcagg
     5341 acagctgtcc gtcattgctg cttgatcatg ctgatgtggt gaactgtacc tctataggcc
     5401 caggtctcat gaagtgtgct atcacttgtc aaaggggatt tgcccttcag gccagcagtg
     5461 ggcagtacat caggcccatg cagaaggaaa ttctgctcac atgttcttct gggcactggg
     5521 accagaatgt gagctgcctt cccgtggact gcggtgttcc cgacccgtct ttggtgaact
     5581 atgcaaactt ctcctgctca gagggaacca aatttctgaa acgctgctca atctcttgtg
     5641 tcccaccagc caagctgcaa ggactgagcc catggctgac atgtcttgaa gatggtctct
     5701 ggtctctccc tgaagtctac tgcaagttgg agtgtgatgc tccccctatt attctgaatg
     5761 ccaacttgct cctgcctcac tgcctccagg acaaccacga cgtgggcacc atctgcaaat
     5821 atgaatgcaa accagggtac tatgtggcag aaagtgcaga gggtaaagtc aggaacaagc
     5881 tcctgaagat acaatgcctg gaaggtggaa tctgggagca aggcagctgc attcctgtgg
     5941 tgtgtgagcc accccctcct gtgtttgaag gcatgtatga atgtaccaat ggcttcagcc
     6001 tggacagcca gtgtgtgctc aactgtaacc aggaacgtga aaagcttccc atcctctgca
     6061 ctaaagaggg cctgtggacc caggagttta agttgtgtga gaatctgcaa ggagaatgcc
     6121 caccaccccc ctcagagctg aattctgtgg agtacaaatg tgaacaagga tatgggattg
     6181 gtgcagtgtg ttccccattg tgtgtaatcc cccccagtga ccccgtgatg ctacctgaga
     6241 atatcactgc tgacactctg gagcactgga tggaacctgt caaagtccag agcattgtgt
     6301 gcactggccg gcgtcaatgg cacccagacc ccgtcttagt ccactgcatc cagtcatgtg
     6361 agcccttcca agcagatggt tggtgtgaca ctatcaacaa ccgagcctac tgccactatg
     6421 acgggggaga ctgctgctct tccacactct cctccaagaa ggtcattcca tttgctgctg
     6481 actgtgacct ggatgagtgc acctgccggg accccaaggc agaagaaaat cagtaactgt
     6541 gggaacaagc ccctccctcc actgcctcag aggcagtaag aaagagaggc cgacccagga
     6601 ggaaacaaag ggtgaatgaa gaagaacaat catgaaatgg aagaaggagg aagagcatga
     6661 aggatcttat aagaaatgca agaggatatt gataggtgtg aactagttca tcaagtagcc
     6721 caagtaggag agaatcatag gcaaaagttt ctttaaagtg gcagttgatt aacatggaag
     6781 gggaaatatg atagatatat aaggaccctc ctccctcact tatattctat taaatcctat
     6841 cctcaactct tgccctgctc tccgctccac cccctgccaa ctactcagtc ccacccaact
     6901 tgtaaaccaa taccaaaata ctagaggaga agttggcagg gatactgtta atacccattt
     6961 tgaatggatt gccatctttc agagcttgtc tgctctcaac tggctctttt tctttttgtg
     7021 tagtttccct taaataatga agttagttat taattcttta taagtattta aacataatta
     7081 tataaatata ttatatatat tatatttttt gctgtttact aagctaaaaa ttattcattg
     7141 ttccacacat gctgctgtga agttcacatt caagatgaat gttgagactt tgaggacaga
     7201 aaggcaactt attttcccat ctttctatgg atgcggattg gcaggttgaa tgggaagtac
     7261 agaaggagag agagtaatta gatggaattc tggatgctag catgtaaagc taatcatctt
     7321 tttttttatg acctgggagc tgggcccatt ttatgaccaa ggagatgggg agttggaatg
     7381 gtggtactaa gaggcatagg aagttgagtg tgaataccat tggtgatggg tccaggagaa
     7441 ctagactatg gttcttgaat atctgtccac aaagaatata ctaacttttg tcaacttctc
     7501 agaactccca actggagtcg gtgagaccta ggattttctg cacttccaca catgcctgtt
     7561 ccaagtgtgg ctgtcagcca gtcaacaagt ttgtactatg gcccattctc tgatcaccag
     7621 gattacagga actcacacac tcctcatact tggcctgtag tcctacttct tgttagaagt
     7681 ctccaagtct ggccagtcac atgaccaagt gttgattttt ctggaggaaa aattttatgg
     7741 aaatgatata ggggaaaggt gggaggagat gaaagaacag gcaagagctg tcagggttaa
     7801 atccaggccc gggcatgaga atggaagtga tcagggagac tcggtccttg ttccaagtct
     7861 ccaaagaaga ccaaagtggg tcccttgagc aatgaagaat ctgagataaa ttctcttcaa
     7921 gtatcatgta caaaatctgt gagccagaga ttttgacttg agcaagccat ggaaatgcat
     7981 ggagcaaggg tgacactctg tggggagaca gaagaatttc aactatttaa tgtccatttt
     8041 gttgttttta ccctttctta tccaatagat ggaatgcaca tgaaatgacc atattaagcc
     8101 tctctctatt tacatcccag gctcactggg atgtgatcta ctgcagttac attttcttgt
     8161 aacggtttct ggattagacc ctagggaaag tgagtaagga gccagtttct gtttaacatt
     8221 ctagttttac tcattttagg aaggctgtga gtgaggcttg tctcctttaa agtttcttct
     8281 ccaatggaaa ccaagaacag acaaaattta gagctcagct gtggtctctt ctcatcttct
     8341 gctcttttgc tttgaccaca gtttttctac tcttcccatc aacactagag caatggctgt
     8401 gcaaatagga ataggaaata ctaccacaat gatagaaata ttatccacac tatcacgtag
     8461 ggaagaacaa tatcctgaaa gagaataaaa cacgaataag gtgatgtacc cacattaatc
     8521 tgtgggtttg tggaatgagg gttgcaaagt tattgggaaa aggaaagagc agagttcacc
     8581 cattcaaaaa aaaccttttg tctactaatc tctagtgtaa agaaaatgta gttcagatac
     8641 cattcattgt cttgggtcat gcttagtgcc cccaagaaga caaacatatt tattcttggg
     8701 attctgatag gcttcaatat gcaaaggaca atggaaaagt ttagacactc tattttcaaa
     8761 attttataaa cttgttttat tggggaaaat gtccaaattg ctagacacat tctaagttct
     8821 gccttggaga atcctacttt gtctgagatt gaggcagagg aattgttatc ctgggcatta
     8881 ctcagctcag gaacatggag cctgtggttc atgccagtgt gtgtcttcat gcagtctctc
     8941 cacaagagca acagtaagaa catttctgtt ttaaatttca ttttaaaata ttttattatc
     9001 tgcaattcac cactgctctg ggaaagcaaa aggaaagttc ctgttgtgtg tgaagagcct
     9061 cttaggctat aaggcttccc agccatagtc agctatagct attcagagac agcaggttct
     9121 tccagtcttt gttcctggga cctgatgttt tgagcaactc aggtcactga taaagtggaa
     9181 ggactaagac actgtggtca cagatcccag caacatcaac tcacactcaa tccatgtggt
     9241 ggtccacatt ctgctactct tatccaccca tgtggtcatt gagagccttt ctcagagact
     9301 cttctgtgtg tttgattgtg cccaggtggc ccagggctag ctggctctaa caactagcat
     9361 gacagcctcc aatcagaaag gcaggtaagg ggacagggtg aggagaatgg gcagatactg
     9421 acagaaatta aagtaaaggg attgtgaaag taaagagctc ttcctgattc tcatcttctc
     9481 ttttttctat tacaaggcat tgaacttggc acttcctgta ttctttgtga tcactattga
     9541 gtgcattagt taacacccaa ggggatggct tgattgggaa tgtagtgaaa ggagctgatc
     9601 tactgtattg taatgtaaaa cagctacagc cagttatttt gtaagattat aagttgttca
     9661 ttaaaaaatc agcacacaaa ata
//
