LOCUS       NM_002581              10971 bp    mRNA    linear   PRI 24-OCT-2024
DEFINITION  Homo sapiens pappalysin 1 (PAPPA), mRNA.
ACCESSION   NM_002581 NM_175615
VERSION     NM_002581.5
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 10971)
  AUTHORS   Dya,G.A., Lebedeva,O.S., Gushchevarov,D.A., Volovikov,E.A.,
            Belikova,L.D., Kopylova,I.V., Postnikov,A.B., Artemieva,M.M.,
            Medvedeva,N.A., Lagarkova,M.A., Katrukha,A.G. and Serebryanaya,D.V.
  TITLE     Specific cleavage of IGFBP-4 by papp-a in nervous tissue
  JOURNAL   Biochem Biophys Res Commun 733, 150655 (2024)
   PUBMED   39244846
  REMARK    GeneRIF: Specific cleavage of IGFBP-4 by papp-a in nervous tissue.
REFERENCE   2  (bases 1 to 10971)
  AUTHORS   Heinosalo,T., Saarinen,N., Biehl,A., Rytkonen,K.T., Villa,P.M.,
            Juhila,J., Koskimies,P., Laiho,A., Hamalainen,E., Kajantie,E.,
            Raikkonen,K., Elo,L.L., Laivuori,H. and Poutanen,M.
  TITLE     Serum hydroxysteroid (17beta) dehydrogenase 1 concentration in
            pregnant women correlates with pregnancy-associated plasma protein
            A but does not serve as an independent marker for
            preeclampsiadagger
  JOURNAL   Biol Reprod 111 (2), 436-447 (2024)
   PUBMED   38780059
  REMARK    GeneRIF: Serum hydroxysteroid (17beta) dehydrogenase 1
            concentration in pregnant women correlates with
            pregnancy-associated plasma protein A but does not serve as an
            independent marker for preeclampsiadagger.
REFERENCE   3  (bases 1 to 10971)
  AUTHORS   He,Y., Yang,X. and Wu,N.
  TITLE     TGFbeta1, SNAIL2, and PAPP-A Expression in Placenta of Gestational
            Diabetes Mellitus Patients
  JOURNAL   J Diabetes Res 2024, 1386469 (2024)
   PUBMED   39109165
  REMARK    GeneRIF: TGFbeta1, SNAIL2, and PAPP-A Expression in Placenta of
            Gestational Diabetes Mellitus Patients.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 10971)
  AUTHORS   Borna,S., Ashrafzadeh,M., Ghaemi,M., Eshraghi,N., Hivechi,N. and
            Hantoushzadeh,S.
  TITLE     Correlation between PAPP-A serum levels in the first trimester of
            pregnancy with the occurrence of gestational diabetes, a
            multicenter cohort study
  JOURNAL   BMC Pregnancy Childbirth 23 (1), 847 (2023)
   PUBMED   38082246
  REMARK    GeneRIF: Correlation between PAPP-A serum levels in the first
            trimester of pregnancy with the occurrence of gestational diabetes,
            a multicenter cohort study.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 10971)
  AUTHORS   Balkas,G. and Caglar,T.
  TITLE     Elevated first-trimester PAPP-A is a marker in high-risk
            pregnancies with an increased risk of placenta accreta in
            predicting adverse outcomes
  JOURNAL   Eur Rev Med Pharmacol Sci 27 (20), 9955-9961 (2023)
   PUBMED   37916365
  REMARK    GeneRIF: Elevated first-trimester PAPP-A is a marker in high-risk
            pregnancies with an increased risk of placenta accreta in
            predicting adverse outcomes.
REFERENCE   6  (bases 1 to 10971)
  AUTHORS   Oxvig,C.
  TITLE     The role of PAPP-A in the IGF system: location, location, location
  JOURNAL   J Cell Commun Signal 9 (2), 177-187 (2015)
   PUBMED   25617049
REFERENCE   7  (bases 1 to 10971)
  AUTHORS   Sinosich,M.J. and Zakher,A.
  TITLE     Pregnancy-associated plasma protein A interaction with heparin: a
            critical appraisal
  JOURNAL   Gynecol Obstet Invest 32 (2), 72-77 (1991)
   PUBMED   1721035
REFERENCE   8  (bases 1 to 10971)
  AUTHORS   Sinosich,M.J. and Saunders,D.M.
  TITLE     Potential role of pregnancy-associated plasma protein-A in human
            reproduction
  JOURNAL   J Reprod Immunol 10 (1), 55-65 (1987)
   PUBMED   2438405
REFERENCE   9  (bases 1 to 10971)
  AUTHORS   Bolton,A.E., Pinto-Furtado,L.G., Andrew,C.E. and Chapman,M.G.
  TITLE     Measurement of the pregnancy-associated proteins, placental protein
            14 and pregnancy-associated plasma protein A in human seminal
            plasma
  JOURNAL   Clin Reprod Fertil 4 (3), 233-240 (1986)
   PUBMED   2427179
REFERENCE   10 (bases 1 to 10971)
  AUTHORS   Bischof,P. and Tseng,L.
  TITLE     In vitro release of pregnancy-associated plasma protein-A (PAPP-A)
            by human endometrial cells
  JOURNAL   Am J Reprod Immunol Microbiol 10 (4), 139-142 (1986)
   PUBMED   2422961
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL691426.9, BY795841.2,
            BC078657.1, X68280.1, AK300129.1, AU134599.1, AL137024.27 and
            AY623010.1.
            
            On Nov 23, 2018 this sequence version replaced NM_002581.4.
            
            Summary: This gene encodes a secreted metalloproteinase which
            cleaves insulin-like growth factor binding proteins (IGFBPs).
            Following IGFBP cleavage, insulin growth factors dissociate from
            IGFBPs and bind to IGF receptors, resulting in activation of the
            IGF pathway. The encoded protein plays a role in bone formation,
            inflammation, wound healing and female fertility. Enhanced
            expression of this protein is associated with diabetic nephropathy
            in human patients and this protein may promote tumor invasion and
            growth in various human cancers. [provided by RefSeq, Aug 2017].
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript 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 :: BC078657.1, SRR1660803.213527.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1968968
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000328252.4/ ENSP00000330658.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1                 AL691426.9         169795-169795
            2-371               BY795841.2         21-390
            372-797             BC078657.1         1-426
            798-1860            X68280.1           188-1250
            1861-4052           BC078657.1         1490-3681
            4053-4053           AK300129.1         983-983
            4054-5184           BC078657.1         3683-4813
            5185-5675           AU134599.1         56-546
            5676-10553          AL137024.27        119798-124675
            10554-10971         AY623010.1         1413-1830
FEATURES             Location/Qualifiers
     source          1..10971
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="9"
                     /map="9q33.1"
     gene            1..10971
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /note="pappalysin 1"
                     /db_xref="GeneID:5069"
                     /db_xref="HGNC:HGNC:8602"
                     /db_xref="MIM:176385"
     exon            1..797
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     CDS             383..5266
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /EC_number="3.4.24.79"
                     /note="aspecific BCL2 ARE-binding protein 2;
                     pregnancy-associated plasma protein A, pappalysin 1;
                     insulin-like growth factor-dependent IGF binding protein-4
                     protease; differentially placenta 1 expressed protein;
                     IGF-dependent IGFBP-4 protease"
                     /codon_start=1
                     /product="pappalysin-1 preproprotein"
                     /protein_id="NP_002572.2"
                     /db_xref="CCDS:CCDS6813.1"
                     /db_xref="GeneID:5069"
                     /db_xref="HGNC:HGNC:8602"
                     /db_xref="MIM:176385"
                     /translation="MRLWSWVLHLGLLSAALGCGLAERPRRARRDPRAGRPPRPAAGP
                     ATCATRAARGRRASPPPPPPPGGAWEAVRVPRRRQQREARGATEEPSPPSRALYFSGR
                     GEQLRLRADLELPRDAFTLQVWLRAEGGQRSPAVITGLYDKCSYISRDRGWVVGIHTI
                     SDQDNKDPRYFFSLKTDRARQVTTINAHRSYLPGQWVYLAATYDGQFMKLYVNGAQVA
                     TSGEQVGGIFSPLTQKCKVLMLGGSALNHNYRGYIEHFSLWKVARTQREILSDMETHG
                     AHTALPQLLLQENWDNVKHAWSPMKDGSSPKVEFSNAHGFLLDTSLEPPLCGQTLCDN
                     TEVIASYNQLSSFRQPKVVRYRVVNLYEDDHKNPTVTREQVDFQHHQLAEAFKQYNIS
                     WELDVLEVSNSSLRRRLILANCDISKIGDENCDPECNHTLTGHDGGDCRHLRHPAFVK
                     KQHNGVCDMDCNYERFNFDGGECCDPEITNVTQTCFDPDSPHRAYLDVNELKNILKLD
                     GSTHLNIFFAKSSEEELAGVATWPWDKEALMHLGGIVLNPSFYGMPGHTHTMIHEIGH
                     SLGLYHVFRGISEIQSCSDPCMETEPSFETGDLCNDTNPAPKHKSCGDPGPGNDTCGF
                     HSFFNTPYNNFMSYADDDCTDSFTPNQVARMHCYLDLVYQGWQPSRKPAPVALAPQVL
                     GHTTDSVTLEWFPPIDGHFFERELGSACHLCLEGRILVQYASNASSPMPCSPSGHWSP
                     REAEGHPDVEQPCKSSVRTWSPNSAVNPHTVPPACPEPQGCYLELEFLYPLVPESLTI
                     WVTFVSTDWDSSGAVNDIKLLAVSGKNISLGPQNVFCDVPLTIRLWDVGEEVYGIQIY
                     TLDEHLEIDAAMLTSTADTPLCLQCKPLKYKVVRDPPLQMDVASILHLNRKFVDMDLN
                     LGSVYQYWVITISGTEESEPSPAVTYIHGSGYCGDGIIQKDQGEQCDDMNKINGDGCS
                     LFCRQEVSFNCIDEPSRCYFHDGDGVCEEFEQKTSIKDCGVYTPQGFLDQWASNASVS
                     HQDQQCPGWVIIGQPAASQVCRTKVIDLSEGISQHAWYPCTISYPYSQLAQTTFWLRA
                     YFSQPMVAAAVIVHLVTDGTYYGDQKQETISVQLLDTKDQSHDLGLHVLSCRNNPLII
                     PVVHDLSQPFYHSQAVRVSFSSPLVAISGVALRSFDNFDPVTLSSCQRGETYSPAEQS
                     CVHFACEKTDCPELAVENASLNCSSSDRYHGAQCTVSCRTGYVLQIRRDDELIKSQTG
                     PSVTVTCTEGKWNKQVACEPVDCSIPDHHQVYAASFSCPEGTTFGSQCSFQCRHPAQL
                     KGNNSLLTCMEDGLWSFPEALCELMCLAPPPVPNADLQTARCRENKHKVGSFCKYKCK
                     PGYHVPGSSRKSKKRAFKTQCTQDGSWQEGACVPVTCDPPPPKFHGLYQCTNGFQFNS
                     ECRIKCEDSDASQGLGSNVIHCRKDGTWNGSFHVCQEMQGQCSVPNELNSNLKLQCPD
                     GYAIGSECATSCLDHNSESIILPMNVTVRDIPHWLNPTRVERVVCTAGLKWYPHPALI
                     HCVKGCEPFMGDNYCDAINNRAFCNYDGGDCCTSTVKTKKVTPFPMSCDLQGDCACRD
                     PQAQEHSRKDLRGYSHG"
     exon            798..1860
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            1861..2006
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            2007..2300
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            2301..2493
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            2494..2615
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            2616..3114
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            3115..3243
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            3244..3335
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            3336..3529
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            3530..3643
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            3644..3779
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            3780..3993
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            3994..4162
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            4163..4346
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            4347..4557
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            4558..4729
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            4730..4877
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            4878..4987
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            4988..5059
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            5060..5158
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     exon            5159..10971
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5677..5682
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /note="hexamer: AATAAA"
     polyA_site      5702
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
     regulatory      10947..10952
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /note="hexamer: AATATA"
     polyA_site      10971
                     /gene="PAPPA"
                     /gene_synonym="ASBABP2; DIPLA1; IGFBP-4ase; PAPA; PAPP-A;
                     PAPPA1"
                     /note="major polyA site"
ORIGIN      
        1 agagcatctt ttggggggag ggaattcagc ggatcagtct taagaggagc ttttttttgg
       61 agcgagaaat catataaaat aaaatgaaat aaaacaagga ggaaggcaac cagctgttag
      121 gggaaaaata aggcagataa aggagcgggg agagaaatta attgccaacc aggaggagtt
      181 gggctgtatt tttcaaaggt ggggagagtg gagcacacac cttgaggagg aaagcgagaa
      241 agaaaagaaa aaagcaagtg gaaagggggg ctcgcccaag aagggtgaag aagcgaagaa
      301 agtcgaggcg ccgaggctcc caaagctggc agctccgggt ggcggtgcag gggcgaaggg
      361 ggggcggggg gaaccgtcgg acatgcggct ctggagttgg gtgctgcacc tggggctgct
      421 gagcgccgcg ctgggctgcg ggctggccga gcgtccccgc cgggcccgga gagacccgcg
      481 ggccggccga cccccgcgcc ccgccgccgg cccggccacc tgcgccaccc gggcggcccg
      541 cggccgccgc gcctcgccgc cgccgccgcc gccgccgggc ggtgcctggg aagccgtgcg
      601 cgtcccccgg cggcggcagc agcgggaggc gaggggcgcc accgaggagc cgagcccgcc
      661 gagccgggcg ctctatttca gcgggcgagg cgagcagctg cgcctccggg ccgacctcga
      721 gctgccccgg gacgcgttca cgctgcaagt gtggctgcga gcggaggggg gccagaggtc
      781 tccggcagtg atcacagggc tgtatgacaa atgttcttat atctcacgtg accgaggatg
      841 ggtcgtgggc attcacacca tcagtgacca agacaacaaa gacccacgct actttttctc
      901 cttgaagaca gaccgagccc ggcaagtgac caccatcaat gcccaccgca gctacctccc
      961 aggccagtgg gtatacctag ctgccaccta tgatgggcag ttcatgaagc tctatgtgaa
     1021 tggtgcccag gtggccacct ctggggaaca agtgggtggc atattcagcc cactgaccca
     1081 gaagtgcaaa gtgctcatgt tagggggcag tgccctgaat cacaactacc ggggctacat
     1141 cgagcacttc agtctgtgga aggtggccag gactcagcgg gagatactgt ctgacatgga
     1201 aacccatggc gcccacactg ctctacctca gctcctcctc caggagaact gggacaatgt
     1261 gaagcatgcc tggtccccca tgaaggatgg cagcagcccc aaagtggaat tcagcaatgc
     1321 ccacggcttt ctgctggaca cgagtctgga gcctcctctg tgcggacaga cattgtgtga
     1381 caacacagag gtcattgcca gctacaatca gctctcaagt ttccgccagc ccaaggtggt
     1441 gcgctaccgc gtggtcaacc tctatgaaga tgatcataag aacccgacgg tgacgcgcga
     1501 gcaggtggac ttccagcacc atcagctggc tgaggccttc aagcaataca acatctcctg
     1561 ggagctggac gtgctggagg tgagcaactc ctcccttcgc cgccgcctca tcctggccaa
     1621 ctgtgacatc agcaagattg gggatgagaa ctgtgacccc gagtgcaacc acacgctgac
     1681 gggccacgac ggcggggatt gccgccacct gcgccaccct gccttcgtga agaagcagca
     1741 caacggggtg tgtgacatgg actgcaacta tgaacggttc aactttgatg gtggagagtg
     1801 ctgtgaccct gaaatcacca atgtcactca gacttgcttt gaccccgact ctccacacag
     1861 agcctacttg gatgttaatg agctgaagaa cattcttaaa ttggatggat caacacatct
     1921 caatattttc tttgcaaaat cctcagagga ggagttggca ggagtagcaa cttggccatg
     1981 ggacaaggag gccctgatgc acttaggtgg cattgtcttg aacccatctt tctatggcat
     2041 gcctgggcac acccacacca tgatccatga gattggtcac agcctgggcc tctatcacgt
     2101 cttccgaggc atctcagaaa tccagtcctg cagtgacccc tgcatggaga cagagccctc
     2161 cttcgagact ggagacctct gcaatgatac caacccagcc cctaaacaca agtcctgtgg
     2221 tgacccaggg ccaggaaatg acacctgtgg ctttcatagc ttcttcaaca ctccttacaa
     2281 caacttcatg agctatgcag atgacgactg tacggactcc ttcacgccca atcaagtcgc
     2341 cagaatgcac tgttacctgg acctggtcta ccagggctgg cagccctcca ggaaaccagc
     2401 gcctgttgcc ctcgcccccc aagttctggg ccacacaacg gactctgtga cactggagtg
     2461 gttcccacct atagatggcc atttctttga aagagaattg ggatcagcat gtcatctttg
     2521 cctggaaggg agaatcctgg tgcagtatgc ttccaacgct tcctccccaa tgccctgcag
     2581 cccatcagga cactggagcc ctcgtgaagc agaaggtcat cctgatgttg aacagccctg
     2641 taagtccagt gtccgcacct ggagcccaaa ttcagctgtc aacccacaca cggttcctcc
     2701 agcctgccct gagcctcaag gctgctacct cgagctggag ttcctctacc ccttggtccc
     2761 tgagtctctg accatttggg tgacctttgt ctccactgac tgggactcta gtggagctgt
     2821 caatgacatc aaactgttgg ctgtcagtgg gaagaacatc tccctgggtc ctcagaatgt
     2881 cttctgtgat gtcccactga ccatcagact ctgggacgtg ggcgaggagg tgtatggcat
     2941 ccaaatctac acgctggatg agcacctgga gatcgatgct gccatgttga cctccactgc
     3001 agacacccca ctctgtctac agtgtaagcc cctgaagtat aaggtggtcc gggaccctcc
     3061 tctccagatg gatgtggcct ccatcctaca tctcaatagg aaattcgtag acatggatct
     3121 aaatcttggc agtgtgtacc agtattgggt cataactatt tcaggaactg aagagagtga
     3181 gccatcacct gctgtcacat acatccatgg aagtgggtac tgtggcgatg gcattataca
     3241 aaaagaccaa ggtgaacaat gcgacgacat gaataagatc aatggtgatg gctgctccct
     3301 tttctgccga caagaagtct ccttcaattg tattgatgaa cccagccggt gctatttcca
     3361 tgatggtgat ggggtatgtg aggagtttga acaaaaaacc agcattaagg actgtggtgt
     3421 ctacacgccc cagggattcc tggatcagtg ggcatccaat gcttcagtat ctcatcaaga
     3481 ccagcaatgc ccaggctggg tcatcatcgg acagccagca gcatcccagg tgtgtcgaac
     3541 caaggtgata gatctcagtg aaggcatttc ccagcatgcc tggtaccctt gcaccatcag
     3601 ctacccatat tcccagctgg ctcagaccac tttttggctc cgggcgtatt tttctcaacc
     3661 aatggttgcc gcagctgtca ttgtccacct ggtgacggat gggacatatt atggggacca
     3721 aaagcaggag accatcagcg tgcagctgct tgataccaaa gatcagagcc acgatctagg
     3781 cctccatgtc ctgagctgca ggaacaatcc cctgattatc cctgtggtcc atgacctcag
     3841 ccagcccttc taccacagcc aggcggtacg tgtgagcttc agttcgcccc tggtcgccat
     3901 ctcgggggtg gccctccgtt ccttcgacaa ctttgacccc gtcaccctga gcagctgcca
     3961 gagaggggag acctacagcc ctgccgagca gagctgcgtg cacttcgcat gtgagaaaac
     4021 tgactgtcca gagctggctg tggagaatgc ttctctcaat tgctccagca gcgaccgcta
     4081 ccacggtgcc cagtgtactg tgagctgccg gacaggctac gtgctccaga tacggcggga
     4141 tgatgagctg atcaagagcc agacgggacc cagcgtcaca gtgacctgta cagagggcaa
     4201 gtggaataag caggtggcct gtgagccagt cgactgcagc atcccagatc accatcaagt
     4261 ctatgctgcc tccttctcct gccctgaggg caccaccttt ggcagtcaat gttccttcca
     4321 gtgccgtcac cctgcacaat tgaaaggcaa caacagcctc ctgacctgca tggaggatgg
     4381 gctgtggtcc ttcccagagg ccctgtgtga gctcatgtgc ctcgctccac cccctgtgcc
     4441 caatgcagac ctccagaccg cccggtgccg agagaataag cacaaggtgg gctccttctg
     4501 caaatacaaa tgcaagcctg gataccatgt gcctggatcc tctcggaagt caaagaaacg
     4561 ggccttcaag actcagtgta cccaggatgg cagctggcag gagggagctt gtgttcctgt
     4621 gacctgtgac ccacctccac caaaattcca tgggctctac cagtgtacta atggcttcca
     4681 gttcaacagt gagtgtagga tcaagtgtga agacagtgat gcctcccagg gacttgggag
     4741 caatgtcatt cattgccgga aagatggcac ctggaacggc tccttccatg tctgccagga
     4801 gatgcaaggc cagtgctcgg ttccaaacga gctcaacagc aacctcaaac tgcagtgccc
     4861 tgatggctat gccatagggt cggagtgtgc cacctcgtgc ctggaccaca acagcgagtc
     4921 catcatcctg ccaatgaacg tgaccgtgcg tgacatcccc cactggctga accccacacg
     4981 ggtagagaga gttgtctgca ctgctggtct caagtggtat cctcaccctg ctctgattca
     5041 ctgtgtcaaa ggctgtgagc ccttcatggg agacaattat tgtgatgcca tcaacaaccg
     5101 agccttttgc aactatgacg gtggggattg ctgcacctcc acagtgaaga ccaaaaaggt
     5161 caccccattc cctatgtcct gtgatctaca aggtgactgt gcttgtcggg acccccaggc
     5221 ccaagaacac agccggaaag acctccgggg atacagccat ggctaaggaa ggacaagaag
     5281 ttgtcaaaga attcccaacg ccaggaccca catccctttg gtattgattt cacagtcagc
     5341 tgctcaacgg aatggcctct ccacaccagg gatccttagc acccaaccgg tctgccttta
     5401 attttaccca ggaaggactc acattggggc gaatgaacca agtttcgcca tgctggatga
     5461 tgaaatggat tcccatccca aagtctgaga tggattgcat atacagtgtg cagtcccaga
     5521 gcctcctaaa attctagcca tttgtcacac aaccacagca agaaacgtgt tctatatcta
     5581 gagtgtgccc atctgtgttt agtacacatg catgcataca cacccataca aacatctgtg
     5641 tgagggcagt tctggagatg agcagagaga gaccggaata aactcaatct tttctttccc
     5701 aagctcctag ccaacactat ccttgggaga aagaaatttg cagaaactgc taagaccaag
     5761 tgtggagatg tcaagctagt tcacactctg aggctcagaa tatgtaggac atgcacaatt
     5821 gtgcagtcct ttgggattgg aagtgaaaca gtctgtgatc ccctaccttc tagggaacta
     5881 ggacctagga agaggtaaag attatcaggt atgcaaagcg ccccaattct tctgctgcca
     5941 tgggggattt taccccaact ccagggttcg aggccaatct gagaatggct taggattgca
     6001 atgtcaaggt attatatcag ccccttgctt gaggcttgag gtcataatat ccctctagga
     6061 cttacctgtt cccccagatc ttgccttggg accacatttg ctgctacttt tcctgctgct
     6121 ctatcctata cattgaataa tccaagatgg tagaactagg ttaggaaaaa ttccacacaa
     6181 ccaaacagtc tgccttaaaa gtgacccaca tttttccata gctcctcact ttttagccct
     6241 tctgcaagag aaaaaccctc atgggtccac atggtgagaa gttaagtttc ctgtaagtgg
     6301 gcctctcacc ctggaaagga gttgagggac atcagatgct ggaaccctca ctgaaagtcc
     6361 agaatgtcta agccagtgtt agattttgta aacaagtgga acagtgttaa atttctatga
     6421 tgttggagcc atccagagac tactggaatt gtcgagactt ttggattatt atccttatcc
     6481 ttatcctaat cttcctagcc cttcaggcta gagtaggctt tgatcctgag aaccttgctg
     6541 ttgctctgag gagatataat tctgggagaa agaatctttt ataagaacag tacagattgt
     6601 tctcaagagg gccatcagaa ggaagccaaa gagttcacag cctcagcacc aacaactcaa
     6661 catggtcatc atgttttcta tatggttttt ccagctagca gtactccctt ccatacctgt
     6721 gactgggcag tgcttttctc tctcccatgt ctagcctcca aaagttaagt gaaaattagt
     6781 caactgcacg tggaagcccc caccactttg gggatctctt tatttctttt cagccaggga
     6841 cctgtccact ccctttgaat taatatggga agaaattaat acaggatgaa ctggagagaa
     6901 gggttgagtg tggcatactt tctgaaacct ggagctggga attgcggaga agggaaggtc
     6961 tagactagtt acatcacata gggattactg taaatcaagt catctcaagt ctagtgaaga
     7021 cagccaacag aaacaaaacc tagcataggg atagaaaata ccatgcacgt gtgcagcccc
     7081 acctaattcc tgcatccaag gcaggtgttg ttaatctatc atagcactta aaaaaaaaaa
     7141 aaaaaagaga ccaaaaataa ctttaggaac caccatatta tatcactccc aatagcactg
     7201 acctggtgat caaaaacact tgagaagaca tctattggcc atctctggcc aattacacta
     7261 agaaacatat caaggtgctt ttggcacagg tgcccacaaa tacggatgca gtgctgagat
     7321 agtttatgag acttgtacca tttcacaaac tctgaaattg ggttccatat tggcaaggct
     7381 gccacagttg ttaagaataa tcctctatgt ttcttcctca caaaaccata tctcatttat
     7441 atccagacca ttacttcact ataattacaa ggacaaatta ttagcaagaa ataagaatag
     7501 tattagaaga attgatccta ttttgaaccc ctctccagta tcttcacact cttgtcaact
     7561 ctccaggcct ctctcttgcc ctgagttatc agcctgtgtg gtgttaacta ccttagaagg
     7621 tacaagctaa gaaatgtaac agtatcaacc ctcccagttg cttaattata cccataggta
     7681 atacaaaaag ctctgaagac ccaaagatga cattactaat gatgtgattt caggagccac
     7741 agaagaacct taccagcttc cctcaaatca gtccttatcc tctttctatc ttcactccca
     7801 tcatcatcta ttttcacact atccagctaa gcaaagattc ctggaggctg acttgtatct
     7861 tcagactcac agagtgaatt cagctcttct gaatcaagac ccacccagtc tctttcattc
     7921 agacctgttg ctaacaaatt tatatttgcc aaggatatta ggcaaaagag gctacttgat
     7981 tggtggccaa cctcgtgccc acatggaagg tatctttaat agggtctttt caaaccttag
     8041 tggaggaggg tcagctcaat ttgggcaatg catttgttcc cagtttcatt ttcttcctgg
     8101 gaattaactc gtcatttcat tccttcagtc atcttctgtg taggtgaccg gagcactgag
     8161 aggcagctct gatgcactat tgtgtgtcag cagctcaaag gccctaaaac actgaaggtt
     8221 ctgcatctga agtattagat tgttagcagc aaaatatgaa agatgaggtg gacagtcctc
     8281 taagccctat ttagggaagc ttttccaagc cacaatctta actacctacc caaaggattt
     8341 gcattacccc cagattctgt gccaacaacc ttttaaggaa atacagtcct tgggaaatga
     8401 gttttgatgg tgaattgggg tgttaaggaa gggaaagatt gtcatagatg gtagggcttt
     8461 gaaaatgcag ggtatcagct gccactcctg gcttcaacac attgagtcac tgcctagacg
     8521 gttctcttgg tcttattccc atcctggcca atgcttaaat actatttgtt gaaaataatt
     8581 ctttgagaca gatttcagct acctcccttc caggttcgat ttaacttggt tgtaattgtc
     8641 aatttgttgt tataggtctt acctgtgtga aagaaagaaa aagaaagaaa gaaagaaaga
     8701 gaaaggaaat tataaggtca agttaacagt tttgaggttt tgtgtttttt tctggaacta
     8761 cttcaagtga gaaaataaaa aaaaatggtg acaaagctgt acagatagag ataatagaag
     8821 acaaagagat taaaaggaaa taaaaatgca tgattaaaaa ctaagaataa aaaacctatt
     8881 tttatgtttc ctaaaggaaa ttgtttattc tacagcctca gtaggtagac acaaacataa
     8941 agatttccct agaagacata gagtgggatt tgataacact gtctgttatt ttctgtacat
     9001 tgtggtaggt ccaggaaata tgacattttc ccccttgatg tgttattgtt gttgttgggt
     9061 ggggtgggca ttttgtttat ttgtttggtg gcaatcagtg gtagtaggga gtgggagggc
     9121 ttatattggt ttttccagct attaagggga catattgtgt cgttgtgctt ttcacgttat
     9181 aaaatgttta tatttaccag tacagcactg ggctttataa agactgcact cagaaccaca
     9241 ctgcacagtc cagtttttta aaaagctgct acatgacaga caggtaatcc cactgagtga
     9301 gttttgagaa acaaatcaaa cgaagtaaac aagaaacata aaaaccaaat agcaaatgaa
     9361 taaaagcctg ttcttgtaac ttattcaact tttgccaaat tcctaccaat cacttgcttt
     9421 ttaaaagaaa tgtataatag ccaaaagaga aattatgtcc ctgttgtaca gaagttagaa
     9481 tttttgactc caggcagcag tttgctcagt gatcttgaac aagttatcca attgcctcta
     9541 catttgcatc agtttctcta gctgcaaaat ggggataata ctatatacct acctcacagt
     9601 gggagggcag gagattttga ggccctgagg ttttaggtgg gctgtgaggg ccaacgcttg
     9661 acacaaagtc catgggttat tattcaagaa tgcacaggcc catcggcctt ttagaaagac
     9721 aagacaggga gtgcttgttt gatatttcaa ggaataaagc cggagctcct gaattgtagt
     9781 ccaccttaaa agagagacct gtattggaga atattttatt tttttggcaa atttgatctt
     9841 accctttacc agttctataa tttggttaaa agctgattat gtcctacaat gtcaaagtca
     9901 gctaactgtc gtctacttaa gacttctggt catttccaac ttatagagga agggagtctc
     9961 taaaatctct tcttcagaag gcacctcact tctcagactt aaaattccac atcaagtgtt
    10021 ccattaaaag aagataaggc attctgagtg caaacaaatg ggggcttctt aaactacaca
    10081 ccagcagtca gtgaggaaaa ctttgaacaa ttattgagtt gctttcttgg gtctctataa
    10141 tcaataacct gtctgcagat atctatctat ataaagatat tatatataaa tataaattta
    10201 catatatatg cacatgtata tatagttgta catatatgtg tgtatatata tacttaaatg
    10261 taatatttac aaaataaaac tgtgatctcg tctagagaaa atgtattcat attacaaact
    10321 gctcttccat atttatgtac catattatac ctttttatta ttgttataat tattatgggt
    10381 atttctaatt aatatgatgt tgaaacctgt ttggcacctt ctggaagcta ccaaaaaaat
    10441 gacactccat tgaagtgctt aaaagctgtt ctcataagaa ttcttctggc ctattgtaaa
    10501 aaagaaaaaa aaaaagaaaa agaagaaaga cacaaagaaa ataatctaaa caccaaaaac
    10561 taaacacaat tccaatcctt tttctgtacc tcacgcgcat aaatttgctg ctcctatttt
    10621 tttttctgtt tatgtgtttt tatggatcta agttaaatct tttggcaata tataaaaatg
    10681 taaatagtaa actttattta ttaagaatgt catctttttt aatttatatt tacacaattg
    10741 ttcatctaat ttattttttc tatacagttt taaatactca gacatatttt gctgttcatg
    10801 atatttttat cctgttctca tggatttgtt ttcccatact gttttctctg atctcaatta
    10861 caggttggat ctcacaaata ataatgtcag agacagaaat attttgccac tgttgattac
    10921 tatactttaa agttctatat tatgaaaata tataatagct tgtacgcttc a
//
