LOCUS       NM_021362              12475 bp    mRNA    linear   ROD 28-JAN-2025
DEFINITION  Mus musculus pregnancy-associated plasma protein A (Pappa), mRNA.
ACCESSION   NM_021362 XM_131437
VERSION     NM_021362.2
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Mus musculus (house mouse)
  ORGANISM  Mus musculus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE   1  (bases 1 to 12475)
  AUTHORS   Basu,S., Mautner,L., Whiting,K., Hasenpusch-Theil,K., Borkowska,M.
            and Theil,T.
  TITLE     Identification of Pappa and Sall3 as Gli3 direct target genes
            acting downstream of cilia signaling in corticogenesis
  JOURNAL   Cereb Cortex 34 (12) (2024)
   PUBMED   39716738
REFERENCE   2  (bases 1 to 12475)
  AUTHORS   Bale,L.K., West,S.A., Gades,N.M., Baker,D.J. and Conover,C.A.
  TITLE     Gene deletion of Pregnancy-associated Plasma Protein-A (PAPP-A)
            improves pathology and cognition in an Alzheimer's disease mouse
            model
  JOURNAL   Exp Neurol 382, 114976 (2024)
   PUBMED   39349117
REFERENCE   3  (bases 1 to 12475)
  AUTHORS   Li,X., Hager,M., McPherson,M., Lee,M., Hagalwadi,R., Skinner,M.E.,
            Lombard,D. and Miller,R.A.
  TITLE     Recapitulation of anti-aging phenotypes by global, but not by
            muscle-specific, deletion of PAPP-A in mice
  JOURNAL   Geroscience 45 (2), 931-948 (2023)
   PUBMED   36542300
  REMARK    GeneRIF: Recapitulation of anti-aging phenotypes by global, but not
            by muscle-specific, deletion of PAPP-A in mice.
REFERENCE   4  (bases 1 to 12475)
  AUTHORS   Vieira,J.R., Shah,B., Dupraz,S., Paredes,I., Himmels,P.,
            Schermann,G., Adler,H., Motta,A., Gartner,L., Navarro-Aragall,A.,
            Ioannou,E., Dyukova,E., Bonnavion,R., Fischer,A., Bonanomi,D.,
            Bradke,F., Ruhrberg,C. and Ruiz de Almodovar,C.
  TITLE     Endothelial PlexinD1 signaling instructs spinal cord
            vascularization and motor neuron development
  JOURNAL   Neuron 110 (24), 4074-4089 (2022)
   PUBMED   36549270
REFERENCE   5  (bases 1 to 12475)
  AUTHORS   Catela,C., Chen,Y., Weng,Y., Wen,K. and Kratsios,P.
  TITLE     Control of spinal motor neuron terminal differentiation through
            sustained Hoxc8 gene activity
  JOURNAL   Elife 11, e70766 (2022)
   PUBMED   35315772
  REMARK    Publication Status: Online-Only
REFERENCE   6  (bases 1 to 12475)
  AUTHORS   Qureshi,S.T., Lariviere,L., Leveque,G., Clermont,S., Moore,K.J.,
            Gros,P. and Malo,D.
  TITLE     Endotoxin-tolerant mice have mutations in Toll-like receptor 4
            (Tlr4)
  JOURNAL   J Exp Med 189 (4), 615-625 (1999)
   PUBMED   9989976
  REMARK    Erratum:[J Exp Med 1999 May 3;189(9):following 1518]
REFERENCE   7  (bases 1 to 12475)
  AUTHORS   Poltorak,A., He,X., Smirnova,I., Liu,M.Y., Van Huffel,C., Du,X.,
            Birdwell,D., Alejos,E., Silva,M., Galanos,C., Freudenberg,M.,
            Ricciardi-Castagnoli,P., Layton,B. and Beutler,B.
  TITLE     Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations
            in Tlr4 gene
  JOURNAL   Science 282 (5396), 2085-2088 (1998)
   PUBMED   9851930
REFERENCE   8  (bases 1 to 12475)
  AUTHORS   Pilz,A., Woodward,K., Povey,S. and Abbott,C.
  TITLE     Comparative mapping of 50 human chromosome 9 loci in the laboratory
            mouse
  JOURNAL   Genomics 25 (1), 139-149 (1995)
   PUBMED   7774911
REFERENCE   9  (bases 1 to 12475)
  AUTHORS   Van Leuven,F., Torrekens,S. and Van den Berghe,H.
  TITLE     Isolation, characterization and partial sequencing of Pregnancy
            Associated Mouse Protein PAMP1 identifies it as a novel female
            specific protein, unrelated to the alpha-2-macroglobulin family of
            proteinase inhibitors
  JOURNAL   FEBS Lett 322 (3), 219-222 (1993)
   PUBMED   7683611
REFERENCE   10 (bases 1 to 12475)
  AUTHORS   Spies,T. and DeMars,R.
  TITLE     Restored expression of major histocompatibility class I molecules
            by gene transfer of a putative peptide transporter
  JOURNAL   Nature 351 (6324), 323-324 (1991)
   PUBMED   2034277
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AL691491.11 and AL691454.15.
            
            On Feb 8, 2022 this sequence version replaced NM_021362.1.
            
            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 :: AF439513.1, SRR9219382.84371.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN00849382, SAMN00849385
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1192              AL691491.11        49212-50403
            1193-2255           AL691491.11        81073-82135
            2256-2401           AL691491.11        101665-101810
            2402-2695           AL691491.11        106317-106610
            2696-2888           AL691491.11        114719-114911
            2889-3010           AL691491.11        122227-122348
            3011-3509           AL691491.11        130110-130608
            3510-3638           AL691491.11        156604-156732
            3639-3730           AL691491.11        163296-163387
            3731-3924           AL691491.11        187304-187497
            3925-4038           AL691454.15        6836-6949
            4039-4174           AL691454.15        7876-8011
            4175-4388           AL691454.15        10763-10976
            4389-4557           AL691454.15        18709-18877
            4558-4741           AL691454.15        21200-21383
            4742-4952           AL691454.15        28098-28308
            4953-5124           AL691454.15        29643-29814
            5125-5272           AL691454.15        37256-37403
            5273-5382           AL691454.15        40480-40589
            5383-5454           AL691454.15        49224-49295
            5455-5553           AL691454.15        54202-54300
            5554-12475          AL691454.15        65135-72056
FEATURES             Location/Qualifiers
     source          1..12475
                     /organism="Mus musculus"
                     /mol_type="mRNA"
                     /strain="C57BL/6"
                     /db_xref="taxon:10090"
                     /chromosome="4"
                     /map="4 34.14 cM"
     gene            1..12475
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /note="pregnancy-associated plasma protein A"
                     /db_xref="GeneID:18491"
                     /db_xref="MGI:MGI:97479"
     exon            1..1192
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     CDS             787..5661
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /EC_number="3.4.24.79"
                     /note="pappalysin-1; IGF-dependent IGFBP-4 protease;
                     insulin-like growth factor-dependent IGF-binding protein 4
                     protease"
                     /codon_start=1
                     /product="pappalysin-1 precursor"
                     /protein_id="NP_067337.1"
                     /db_xref="CCDS:CCDS18267.1"
                     /db_xref="GeneID:18491"
                     /db_xref="MGI:MGI:97479"
                     /translation="MRLWSWVLRLGLLSAALGCGLAERPRRVRRDPRAVRPPRPAAGP
                     ATCATRAARGRRASPPPPPGGAWEAVRVPRRRQQRAARGAEEPSPPSRALYFSGRGEQ
                     LRLRADLELPRDAFTLQVWLRAEGGQKSPAVITGLYDKCSYTSRDRGWVMGIHTTSDQ
                     GNRDPRYFFSLKTDRARKVTTIDAHRSYLPGQWVHLAATYDGRLMKLYMNGAQVATSA
                     EQVGGIFSPLTQKCKVLMLGGSALNHNFRGHIEHFSLWKVARTQREIVSDMETRGLHT
                     PLPQLLLQENWDNVKRTWSPMKDGNSPQVEFSNAHGFLLDTNLEPPLCGQTLCDNTEV
                     ISSYNQLPSFRQPKVVRYRVVNIYDDHHENPTVSWQQIDFQHQQLAEAFQHYNISWEL
                     EVLNINSSSLRHRLILANCDISKIGDEKCDPECNHTLTGHDGGDCRQLRYPAFMKKQQ
                     NGVCDMDCNYERFNFDGGECCDPDITDVTKTCFDPDSPHRAYLDVNELKNILRLDGST
                     HLNIFFANSSEEELAGVATWPWDKEALMHLGGIVLNPSFYGIPGHTHTMIHEIGHSLG
                     LYHIFRGISEIQSCSDPCMETEPSFETGDLCNDTNPAPKHKFCGDPGPGNDTCGFHGF
                     FNTPYNNFMSYADDDCTDSFTPNQVSRMHCYLDLVYQSWQPSRKPAPVALAPQVVGHT
                     MDSVMLEWFPPIDGHFFERELGSACDLCLEGRILVQYAFNASSPMPCGPSGHWSPREA
                     EGHPDVEQPCKSSVRTWSPNSAVNPHTVPPACPEPQGCYLELEFRYPLVPESLTIWVT
                     FVSSDWDSSGAVNDIKLLTISGKNISLGPQNVFCDIPLTIRLRDVGEEVYGIQIYTLD
                     EHLEIDAAMLTSTVDSPLCLQCKPLQYKVLRDPPLLEDVASLLHLNRRFMDTDLKLGS
                     VYQYRIITISGNEESEPSPAAIYTHGSGYCGDGVIQKDQGEECDDMNKVNGDGCSLFC
                     KQEVSFNCIDEPSRCYFHDGDGMCEEFEQKTSIKDCGVYTPQGFLDQWASNASVSHQD
                     QQCPGWVVIGQPAASQVCRTKVIDLSEGISQHAWYPCTITYPYYHLPQTTFWLQTYFS
                     QPMVAAAVIIHLVTDGTYYGDQKQETISVQLLDTKDQSHDLGLHVLSCRNNPLIIPVV
                     HDLSQPFYHSQAVHVSFSSPLVAISGVALRSFDNFDPVTLSSCQRGETYSPAEQSCVH
                     FACQAADCPELAVGNASLNCSSNHHYHGAQCTVSCQTGYVLQIQRDDELIKSQVGPSI
                     TVTCTEGKWNKQVACEPVDCGIPDHHHVYAASFSCPEGTTFGRRCSFQCRHPAQLKGN
                     NSFLTCMEDGLWSFPEALCELMCLAPPPVPNADLQTARCRENKHKVGSFCKYKCKPGY
                     HVPGSSRKSKKRAFKTQCTQDGSWQEGTCVPVTCDPPPPKFHGLYQCTNGFQFNSECR
                     IKCEDSDASQGRGSNIIHCRKDGTWSGSFHVCREMQGQCSAPNQLNSNLKLQCPDGYA
                     IGSECAISCLDHNSESIILPVNLTVRDIPHWMNPTRVQRIVCTAGLQWYPHPALIHCV
                     KGCEPFMGDNYCDAINNRAFCNYDGGDCCTSTVKTKKVTPFPMSCDLQNDCACRDPEA
                     QEHNRKDLRGYSHG"
     exon            1193..2255
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            2256..2401
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            2402..2695
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            2696..2888
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            2889..3010
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            3011..3509
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            3510..3638
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            3639..3730
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            3731..3924
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            3925..4038
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            4039..4174
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            4175..4388
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            4389..4557
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            4558..4741
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            4742..4952
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            4953..5124
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            5125..5272
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            5273..5382
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            5383..5454
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            5455..5553
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     exon            5554..12475
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /inference="alignment:Splign:2.1.0"
     regulatory      11421..11426
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /note="hexamer: AATATA"
     polyA_site      11448
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /note="major polyA site"
     polyA_site      11556
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
     regulatory      12133..12138
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /note="hexamer: AACAAG"
     polyA_site      12153
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
     regulatory      12453..12458
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
                     /note="hexamer: AATAAA"
     polyA_site      12475
                     /gene="Pappa"
                     /gene_synonym="8430414N03Rik; IGFBP-4ase; PAG1; PAPP-A"
ORIGIN      
        1 gtgttttgag tcggaatgcg aagagcaggg aggaccgtaa gggggtgtgt acagaatttc
       61 attaaattgt tactttaaga ttgtcttctt aaaaacagaa gaagtagaag aagaaagagg
      121 gggtggagaa gctgaaccga aggaaaggag acaaacggca aagtagagga aggctgggtg
      181 gatcggcctc tccaaaccga ttgattggtc atgatccccg cagtttgaac agggactcat
      241 tcaattggga aggtggagtg ctggcgaaca gattagcaca cgcttgttta ctcgtcttct
      301 aagggatttt ttccccctct ttcctttcat ttcgtgaaga aggagggagg ggagggggcg
      361 ggggggagaa gggggctgtg gcttgtgtta taaaggacgc aaaaaataaa taaatgagag
      421 catcttgggg ggagggaggg aattcagccg accagtgtgt tagaggagat tttttttaag
      481 agctagaaat atataaaata aaatgaaata aaacaaggag gaaggcatcc agctgttaga
      541 aggggggata aggcagataa aggagcgggg agagaaatta attgccaacc aggaggagtt
      601 ggactgtatt tttgaaaggt ggggggagtg gagcacacac cttgaggagg aaagcgagaa
      661 agaaaagaaa aaagcaagtg gaaggggggc tcgcacgaga aaggaggcaa atagtagtgc
      721 gagctaaagc tggcagctcc gggcggcggt gcaggggcgc agggggggcg ggggggaccg
      781 tcggacatgc ggctctggag ttgggtgctg cgcctggggc tgctgagcgc cgcgctgggc
      841 tgcgggctgg ccgagcgccc ccgccgggtc cgaagagacc ctcgggccgt gcgccccccg
      901 cgccccgccg ctggaccggc cacctgcgcc acccgggcgg cccgcggtcg ccgcgcctcg
      961 ccgccgccgc ctccgggcgg tgcctgggaa gccgtgcgcg tcccccggcg gcggcagcag
     1021 cgggcggcga ggggcgccga ggagccgagc ccgcctagcc gggcgctcta tttcagcggg
     1081 cgaggggagc agctgcgcct ccgggccgac ctggagctac cccgcgacgc ctttacactg
     1141 caagtgtggc tgcgagccga gggtggccag aagtctccag cagtgatcac agggctgtat
     1201 gacaaatgtt cttatacctc acgtgatcga ggatgggtca tgggcattca caccaccagt
     1261 gatcaaggca acagagatcc acgctacttt ttctccttga agacagaccg ggccaggaaa
     1321 gtgaccacca ttgatgccca tcgcagctac ctcccaggtc agtgggtaca tctagctgct
     1381 acctatgatg ggcggctgat gaagctctat atgaatggtg cccaggtggc aacttcggct
     1441 gagcaagtag gtggcatatt cagcccactg acccagaagt gtaaagtgct catgttgggg
     1501 ggcagtgctc tgaatcacaa cttccggggc cacattgaac acttcagtct atggaaagta
     1561 gcaagaaccc agcgagagat tgtatccgac atggaaaccc gtggcctcca cacccctcta
     1621 cctcagctcc tcctccagga gaactgggac aacgtgaagc gcacttggtc ccccatgaag
     1681 gatggcaaca gcccccaggt ggaattcagc aatgcccacg gcttcctgtt ggacactaat
     1741 ttggagcccc ctctttgtgg gcagacactg tgtgacaaca cagaagtcat ctccagttac
     1801 aatcagctcc caagttttcg gcagcccaag gtggtccgct atcgtgtggt caacatctat
     1861 gatgatcacc atgagaatcc aacggtgagc tggcaacaga ttgactttca gcaccaacag
     1921 ctggctgagg cctttcaaca ctacaacatc tcctgggagc tggaggtact gaatataaac
     1981 agttcctctc tgcgtcaccg cctcatccta gccaactgtg acatcagcaa gattggggat
     2041 gaaaaatgtg atccagaatg taaccataca ctgactggtc atgatggtgg agattgccgc
     2101 cagctgcgct accctgcgtt catgaagaag cagcagaatg gtgtgtgtga catggactgt
     2161 aactacgaaa ggtttaattt tgatggtgga gagtgctgtg acccagacat cactgatgtc
     2221 actaagacat gctttgatcc tgactctcca cacagagcct acttggatgt taatgagcta
     2281 aagaacattc ttagactgga cggatcaaca catctcaata ttttctttgc aaactcttca
     2341 gaggaggagt tggcaggagt ggcaacttgg ccatgggaca aggaagccct aatgcacttg
     2401 ggcggtattg tcttgaaccc atctttctat ggcattcccg gacacaccca caccatgatt
     2461 catgagattg ggcatagcct gggcctctat cacatcttcc gtggcatctc agaaatccag
     2521 tcctgcagtg atccctgcat ggagacagag ccttcatttg aaactggaga cctctgcaat
     2581 gataccaacc cagcccccaa acacaagttt tgtggagacc ctggaccagg gaatgacact
     2641 tgtggctttc atggcttctt caacactcct tacaacaact tcatgagcta cgcagatgac
     2701 gactgtacag actctttcac gcccaatcaa gtctccagaa tgcactgtta cctggacctc
     2761 gtataccaga gctggcagcc ctccagaaag ccagcacctg tagctcttgc gccccaggtt
     2821 gtggggcaca caatggactc tgtgatgcta gagtggttcc cacccatcga tggccacttc
     2881 tttgaaagag aattgggatc agcatgtgac ctttgcctag aagggagaat cctggtgcaa
     2941 tatgctttca atgcctcctc ccccatgccc tgtggaccgt caggacactg gagtcctcgg
     3001 gaagcagaag gtcacccaga tgttgaacag ccctgtaaat ccagtgtccg aacctggagt
     3061 ccaaattcag ctgtcaaccc acacacagtt cctccagcct gccctgagcc acaaggctgc
     3121 tacctcgagc tggaatttcg ctaccctttg gtccctgagt ctctgaccat ctgggtaacc
     3181 tttgtctcca gtgattggga ctctagtgga gctgtcaatg acatcaaact cttgactatc
     3241 agtggaaaga atatctcttt gggtcctcag aatgttttct gtgatatccc acttaccatc
     3301 agactccggg atgtgggtga ggaggtatat ggcatccaaa tctatactct tgatgagcac
     3361 ctggagattg atgcagcaat gctgacctcc actgtagaca gtccactctg cctacagtgt
     3421 aaacctctgc agtataaagt gcttcgagac ccacctctgc tagaagatgt agcctcatta
     3481 ctccacctca acagaagatt catggacacg gatctgaaac ttggcagtgt gtaccagtac
     3541 cggattatca ccatttcagg aaatgaagag agcgagccat cacctgctgc catatacacc
     3601 cacggaagtg ggtactgtgg tgatggcgtt atccaaaaag accaaggaga agaatgtgac
     3661 gacatgaata aggtcaatgg ggatggctgc tcccttttct gcaagcaaga agtttccttc
     3721 aactgcattg atgaacccag ccggtgctat ttccatgatg gggatgggat gtgtgaagag
     3781 tttgaacaaa aaactagcat taaagactgt ggtgtctaca cgccccaggg tttcctggat
     3841 cagtgggcat ccaatgcttc agtatctcat caagaccagc agtgcccagg ttgggttgtc
     3901 attgggcagc cagcggcatc tcaggtgtgt cgaaccaagg tgatagatct cagtgaaggc
     3961 atttcccagc atgcttggta tccttgcacc attacttacc catactacca tctgcctcag
     4021 accacattct ggctccagac atatttctct cagccaatgg ttgctgcagc tgtaattatt
     4081 cacctggtga ctgatgggac atactatggg gaccaaaagc aagagaccat cagtgtgcag
     4141 ttgcttgata ccaaagatca aagccatgat ctaggcctcc atgtcttgag ctgcagaaac
     4201 aatcccctga ttatccctgt ggtccatgac ctcagccagc ccttctacca cagccaggcg
     4261 gtacatgtga gcttcagttc gcccctggtc gccatctcgg gggtggccct ccgctctttc
     4321 gacaactttg accccgtcac cctgagcagc tgccagagag gagagaccta cagccctgct
     4381 gagcagagct gtgtgcattt tgcctgtcaa gctgccgact gcccagaact ggccgtgggg
     4441 aatgcttctc tcaactgttc cagcaaccac cactaccatg gtgcccagtg cactgtgagc
     4501 tgccagacag gttatgtgct gcagatacag cgggacgatg agctaatcaa gagccaggta
     4561 gggccaagca tcacagtgac atgtaccgag ggcaaatgga acaagcaggt ggcatgtgag
     4621 ccggtggact gtggtatccc agatcaccat cacgtctatg ctgcctcctt ctcctgtcca
     4681 gagggtacca cctttggtag aagatgttct tttcagtgtc gccaccctgc ccagctgaaa
     4741 ggcaacaaca gctttctgac ctgtatggaa gatggactgt ggtccttccc agaggccttg
     4801 tgtgagctca tgtgcctcgc cccaccccca gttcccaatg cggacctaca gacagcccgg
     4861 tgtcgagaga acaagcacaa ggtgggctcc ttctgcaagt acaagtgtaa acctggatac
     4921 cacgtgcctg gctcatctcg gaagtccaag aaacgggctt tcaagactca atgtactcaa
     4981 gatggcagct ggcaagaggg aacttgtgtg ccggtgactt gtgacccacc tccacccaaa
     5041 ttccatgggc tctatcaatg cactaatggc ttccagttca atagtgagtg caggatcaag
     5101 tgtgaagaca gtgatgcctc ccagggccgt gggagcaata tcattcactg ccggaaagat
     5161 ggcacttgga gtggttcctt ccacgtctgc cgagagatgc aaggccagtg ctcagcccca
     5221 aaccaactca acagtaacct caaattgcag tgtcctgatg gctatgcaat agggtcagag
     5281 tgtgccatct cgtgcctgga ccataacagc gagtccatca tccttcccgt taacttgaca
     5341 gtgcgtgaca taccccattg gatgaacccc acacgagtac agaggattgt ctgcactgct
     5401 ggtctccagt ggtatcccca ccctgctctg atccactgtg tcaaaggctg tgagccattc
     5461 atgggagaca actactgtga tgccatcaac aatcgagcct tctgcaacta tgatggtggg
     5521 gactgctgca cctccacagt aaagaccaaa aaggtcactc cctttcctat gtcctgtgac
     5581 ctacaaaatg actgcgcctg tcgagaccct gaggcccaag aacacaaccg gaaagatctt
     5641 cggggatata gccatggcta aggaaagaca ggtgtcaaag atttcccaat gccaggaccc
     5701 gcatccctct ggtattgatt tcacagtctg ctgctcaatg aaatggcctc tccacaccag
     5761 ggatccttag cacccaaccg gtctgccttt aatttcaccc aggaaggacc aactgtgggg
     5821 caatgaactg aatctcacca tgttgaatga tggagtggaa tactatcctg tagtctaaga
     5881 tggattgaac acacggcatg tagacccaga gcctctaaaa attctttcca tttctcaaat
     5941 gaccatagcc caaaagaaca acaaaacggt gtgtgtatca aggagtatgc acatctgtgg
     6001 ttagtacaca ggcatgcatg cacacccatg ccaatgtctg tgtgagggca gaaaacaact
     6061 ggaaaaaaaa aaagaacaaa atccaaaaaa ttcaatcttt cattttccaa gctcccaagg
     6121 aacactgtct ttgggagaag tggtttatag aaattaagac caagtactga aaagccaata
     6181 catctcagat tctaaggctc agaatattgt gtagtgcttt gggactggaa gtgaaatggc
     6241 tgtaatcacc aaccttctag ggaactaggg cttcctaaat ggtaaatatt ccaaggtgtg
     6301 caaagctccc caattttttt gctgccatgg gggttttgtt ccaacaccag ggtgcaaggt
     6361 tgagctggaa atggcttagg actgcagaat taaggtattc tatcagctcc ctgcttgagg
     6421 cttgaggtct tcatacccct tccagattcc acccattttc cagatctgac cttgggacca
     6481 catttgctgc tactcttcct gctgctctgt ccaatacatt gagtgcccta agatggtaga
     6541 actaggttac aacaaactcc atataaccaa gtagactgcc tcaaaagtga ttcatatttt
     6601 cccacagttc ctcacttctt gcccatctat aagaaaaaaa tatccttcat gggcttaagt
     6661 ctttcatgag tagacttctc attctgggaa agagttgagg gatgccagat gctggagccc
     6721 ttctggaaag tccagaatat ctaatccagt gttggatttt ctaatcaagt ggaacagtgt
     6781 taaacttgga aatgctggag ctacccagag actgttggaa tagcaaggac ttaagttatt
     6841 gtccttatcc cagtcttcct agctctctag gctagaagaa gctttggtct tgagactccc
     6901 actattactc caagcagata gagttgtgaa acatcttgga cattggcgat gtcgactgta
     6961 tactagaaga acatggaagg gaagccctgg agatccagac tgagtaccca acatagtcat
     7021 catattttcc acataatctt tcagatgtta ggacatcttt ccacattcat tgttggacat
     7081 cactccttcc cctcccatat ttagtcttta aatgttaaga ggaaatgagt caactgtaca
     7141 tggaagccag caatatatgc agggcctttt ttcctgcctc ttttcatacc tatgtatata
     7201 ctctgaatta atatgggaag agttaacaca ggatgatgtg gatagaatag ctaactttga
     7261 cataatttat gaaaggtggg gcagggaagc aatgatatgg aggatctaaa tgaattatat
     7321 aacagaaaga tgaatagtac atcaactgat cgcaagtcta gtggagataa ccaaccaata
     7381 aaacaaagtc tggaacagaa tgcaaaatgc cagcccatgt gtaagccaca ctgcatctaa
     7441 ggcattaatt gttcaactat cacatccctt tatctactag gaccaacagt aacttagcca
     7501 actgtgtttt catattatga ccaatagctt tttcctactg atcaagaaca ttttaaaagg
     7561 tagctattga ccatctgtgg tccataatat caggaaatgt accaagatgg ttttgcactg
     7621 gtacccacaa ttatggatat aagtgcttat attatgcagc ttgtcctgtc ctttagcttc
     7681 tggggttgaa gtctagagtg gagaagtggc cactaacaca atggtcaagc actttggttc
     7741 ctccaaaagc atatctcata gtgcatttcc ccctgggatt tcttggacca atctttatca
     7801 aaatataaga acaatttttt ttctagtagc tggcccaatt atgatcatct ctccaagatc
     7861 ctcaaacttt tgtcaagcct tcagattcct cttttgctct gatgtgctgt gtcagcttag
     7921 aagggacaag caaaagagtg gtgacagggc catccttcca gataagtaat ccagaaacct
     7981 ccaaagaccc aaagatgaca ttatcaatag aagagttgta gaaactaaga aagaccacaa
     8041 gaatttctcc cagtcattcc tcatccaaac cctgttgtcg atgtcactgt catctgctct
     8101 tatcctttcc agctgggcaa agattcccgg aggctggctc ctctgttaag attcataggc
     8161 tgaaatgggg gcgggtgggg ggagctttcc aggaagagtc ccatccagtt ttcttctcac
     8221 cgccattcaa gcctgttatg aacaaattca tatttgctga gcctaataga taaaagaggc
     8281 tacccaattg gtagcctgcc tcatgcccac aagggatgtg taattcataa ggtcttctca
     8341 gaccttagtg caggacagtc agctgtattt tttcaatgca ctgattccca gtttcatttt
     8401 cttcctgaga ataaactcct tgtctcatct cctcagtcat ctgttttgga caatgggata
     8461 atcaggagga ggcgggtctg aagcactatt gtacatccac agcttaaggg gctctaaagt
     8521 acttgggagt tctgcagctg aagcagtatg tctgttagca gcaaggaagc aacgaggaga
     8581 tggacagttc tctgagcccc atctggggaa ctgttccaaa ccgcaacaca ctgtctgccc
     8641 ggaggacttg cattaccccc tagattttgt gccaacagcc tcatgaggga agtcagtcag
     8701 tccttgggaa gtcagtgtgg gtaggtgagg tggggtgtaa agcaaaggag agattaacag
     8761 tcttaaatag caggcctttg cagaaggagg gaatcagctg ctgctcttgg ccttagcaca
     8821 ctggacctct gccgagactt ttctgtctca ttcccacatt ggccaatgct taaatgctat
     8881 ttgttgaaaa taattctttg ggacagattt cagctacctc ccttccaggt ttgatttaac
     8941 ttggttgtaa ctgtcaattt gttaaaggtc ttacctgtgt ggattttttt aaaagaaata
     9001 aatagaaaaa gacacgaaag aaaagaaaag aacaggaagg agagcatgtt aaccgtttca
     9061 gtgtgtgtat gtgtgtgtgt gtgtatctct gtgtctttat gtgtgtgtgt gtgtgtgtgt
     9121 gtgatttctt tttttctgaa actacttcaa gtgagaaaat aaatagaagg aattgaaggt
     9181 gacaaagctg taaagactga aattaatagg agacaaagtg attacaaggg actgaaatgc
     9241 atggtgaaaa cctaagaata taagccctat ttttatgctt ccttgaggac actattctat
     9301 aactgagtag gtagagatga catagagatt tctctagaag acttagagtg ggattctatg
     9361 gcattgacta acatttgctg aacattgtgg taggtccagg aagtaaggca tttttgccct
     9421 tgagttattg ttagctaagc attggttcat ttctttagtg actgtccatg gtagagggga
     9481 tgaaggagag tttcatattg atttttacca aatattaagg aaagaaactg ggtctctttg
     9541 tcgtttttac actataagat atttttgttt gccagtatgg cactcagaac cacgctgcac
     9601 agctctgttc ttaagaagct gcttcatgac catgcagggg accccgttga atactgagaa
     9661 agaagacaaa ccaagcaaac aactaaatag agaacaagtt ttctgaaaca cctccttttg
     9721 tgattcattc aagtttttct aaattcctag ctatcatttc ctctgtaaaa acaatgtaat
     9781 aatggtcaag atagaagttg atgtaggtgg cacaaagctc cagaatgctt ttctccagcc
     9841 ttcaatttac tcagtgatct tggagaagtc atcaaattgc ctccatattt gcctcagttt
     9901 ctcttgctga aaaatgggga tacaactagt tacctacctc acagtgggag ggtcatgagg
     9961 ccctgaggat actaaacgga ctgtccaatc tgtagaagac actacacagc ctgaggcaaa
    10021 ggtcataggg ttctttcttt ctttctttct ttctttcttt ctttctttct ttctttcttt
    10081 ctttctttct ttctttcttt tatttcataa aatgcacagg ctcattgccc ttttcagaga
    10141 cagggagtgc ttgatcaaca tttcatggca caaagctgga aggcctgggt tacaatccac
    10201 cttaatgagt gtactgggga atatttactc ttcagataag tttcccctgt gttattctag
    10261 cttttaccaa ttcaatgatt taatcaaaat tcaatggctt cctacagtgt aaaagtcagt
    10321 ctactgtcat ctagttaata ttggggggca cgtttccaat ttacagagta agagggtctg
    10381 gcatctcttc tccagtagaa tcctcacttc tcagacttag tttccacata atctggttca
    10441 ttaagagaag agataacatt ctgagtgcaa gttgggcttc ttaaacttca caccagcagc
    10501 cagtgaggag aactttgaac aattattgag ttgctttctt gggtctctat aatcaataac
    10561 ctatctgcag atatctatct atataaagat attatatata aataaaaatt tacatatata
    10621 tgcacatgta tatatagctg tacatatatg tgtgtatata tatacttaaa tgtaatattt
    10681 acaaaactgt gatctcgtct agagaaaatg tattcatatt acaaactgct cttccatatt
    10741 tatgtatcat attatacctt tttattactg tcataattat tgagggtatt tctaattatt
    10801 atgatgttag aatctgttta gcaccttctg gaagcaatca aaaatatgat ttttcattga
    10861 agtgcttaga atctgttctc atgagaaatc tactggtcta ctgtaaaaca aacaaacaaa
    10921 aattttaaaa aaatgaaaga aaggaagaaa gaaggaaaca aaagagagag agagagagag
    10981 aaaagaaaga ttaaagtaaa gtaaacagca aaaactaaat acaaccctgt tcttcttcct
    11041 gtacctcatg cgcagaaatg tgctgctctt gttttgggtt atttttcctg ttcatgtgtt
    11101 tttatggatc taagttaagt ctttcagcaa tatataaaaa tgtaaatagt taactttatt
    11161 tattaagaat gtcatctttt taaatttata tttacacgat ggttcatcta atttattttt
    11221 tctatacggt ttaaaatact caaacatatt tttctgttca tggtattttt tatgctcttc
    11281 tcatggattt gtgtttccat actgttttct ctggtctcaa ttacaggtta gatctgacac
    11341 acacacatat acacaaataa tgtcaaagac gaatattttg ccactgttga ttactatacc
    11401 ttaaagttct atattatgaa aatatataat agcttgtctg cttcagcatg ttgttgtgtg
    11461 gtttttgact gttatagtca tatagaatgg tcacgcgcgt actcacacaa acacactcac
    11521 acacacatgc aaacataccc atgaaataac ctaaaaggaa acgtgagctt ataataaaaa
    11581 aattcaataa aaagcatgaa attgaattca atatatatca agtgctctat ataattcctg
    11641 aaaagtatct atattttgta catgcaataa ctggcaaata ttattataca ttataatata
    11701 tttccattct atgacactaa catatatact ccttgtcctt atatactgct atttggactc
    11761 tgtcttcaac aatatactct gagaatattt ttattttcat aacaaaaaca cccaaacaac
    11821 aaaaatgaac acaacctgtg ttctggatgt cacactgtca ttgtaatcct gagctcacta
    11881 cagaggttga tactacacaa atccttattt gggttcttca agattacatc ctggatcagg
    11941 attgaggggc tcgttaggat gcctctcgcc ctaaggagct attggcagtt gatggttaca
    12001 gggacagagg gatatcattt tcttcagtgt tgtaagaact ggcaaggggc ccatgctcct
    12061 taaccctctg tccaagctca ttgaagcaaa cctcattaaa taaatgtgag gaccaacaat
    12121 atccacaaca acaacaagtg agaaaactaa caagaaagaa gggcacgtgc agagtcgggg
    12181 aggggagaga gagtgaggca tggatgggat caccacacaa tgtatatgta taaagtttca
    12241 aaatgatgtt atgtgaaaaa taataaatta aaaagtatga acacttaact agccagtcca
    12301 tcgtgtgagc ctccactgag actgaatatt gctgctttct ctctatctag gccattttct
    12361 tgttcatcca cccccagcta gtaagtagct atgcagtctc tggaaagata ttaaattgtt
    12421 ttaaggttct gttttgctat ctgtgaaatg aaaataaaat atcaacttca taata
//
