LOCUS       NM_001304               9372 bp    mRNA    linear   PRI 28-APR-2025
DEFINITION  Homo sapiens carboxypeptidase D (CPD), transcript variant 1, mRNA.
ACCESSION   NM_001304
VERSION     NM_001304.5
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 9372)
  AUTHORS   Thomas,L.N., Chedrawe,E.R., Barnes,P.J. and Too,C.K.L.
  TITLE     Prolactin/androgen-inducible carboxypeptidase-D increases with
            nitrotyrosine and Ki67 for breast cancer progression in vivo, and
            upregulates progression markers VEGF-C and Runx2 in vitro
  JOURNAL   Breast Cancer Res Treat 164 (1), 27-40 (2017)
   PUBMED   28364216
  REMARK    GeneRIF: prolactin induction of VEGF-C and Runx2 was inhibited
            partly by Carboxypeptidase-D inhibitors, implicating nitric oxide ,
            produced by PRL-regulated Carboxypeptidase-D, in breast cancer
            progression
REFERENCE   2  (bases 1 to 9372)
  AUTHORS   Zhao,X., Lu,C., Chu,W., Zhang,Y., Zhang,B., Zeng,Q., Wang,R.,
            Li,Z., Lv,B. and Liu,J.
  TITLE     microRNA-214 Governs Lung Cancer Growth and Metastasis by Targeting
            Carboxypeptidase-D
  JOURNAL   DNA Cell Biol 35 (11), 715-721 (2016)
   PUBMED   27494742
  REMARK    GeneRIF: Carboxypeptidase-D (CPD) overexpression coincides with
            high-grade lung cancer and the CPD overexpression could reverse the
            inhibitory effects of miR-214
REFERENCE   3  (bases 1 to 9372)
  AUTHORS   Garcia-Pardo,J., Grana-Montes,R., Fernandez-Mendez,M., Ruyra,A.,
            Roher,N., Aviles,F.X., Lorenzo,J. and Ventura,S.
  TITLE     Amyloid formation by human carboxypeptidase D transthyretin-like
            domain under physiological conditions
  JOURNAL   J Biol Chem 289 (49), 33783-33796 (2014)
   PUBMED   25294878
  REMARK    GeneRIF: The human carboxypeptidase D transthyretin-like domain
            forms amyloid under physiological conditions.
REFERENCE   4  (bases 1 to 9372)
  AUTHORS   Thomas,L.N., Merrimen,J., Bell,D.G., Rendon,R., Goffin,V. and
            Too,C.K.
  TITLE     Carboxypeptidase-D is elevated in prostate cancer and its
            anti-apoptotic activity is abolished by combined androgen and
            prolactin receptor targeting
  JOURNAL   Prostate 74 (7), 732-742 (2014)
   PUBMED   24615730
  REMARK    GeneRIF: CPD immunostaining and testosterone/prolactin-stimulated
            CPD expression were higher in prostate cancer than benign
            tissues/cells. Elevated CPD increased NO production, which was
            abolished when both androgen and prolactin receptors were
            inhibited.
REFERENCE   5  (bases 1 to 9372)
  AUTHORS   Koirala,S., Thomas,L.N. and Too,C.K.
  TITLE     Prolactin/Stat5 and androgen R1881 coactivate carboxypeptidase-D
            gene in breast cancer cells
  JOURNAL   Mol Endocrinol 28 (3), 331-343 (2014)
   PUBMED   24433040
  REMARK    GeneRIF: Prolactin and R1881, acting through Stat5 and androgen
            receptor, act cooperatively to stimulate CPD gene transcription in
            breast cancer cells.
REFERENCE   6  (bases 1 to 9372)
  AUTHORS   Ishikawa,T., Murakami,K., Kido,Y., Ohnishi,S., Yazaki,Y., Harada,F.
            and Kuroki,K.
  TITLE     Cloning, functional expression, and chromosomal localization of the
            human and mouse gp180-carboxypeptidase D-like enzyme
  JOURNAL   Gene 215 (2), 361-370 (1998)
   PUBMED   9714835
REFERENCE   7  (bases 1 to 9372)
  AUTHORS   Riley,D.A., Tan,F., Miletich,D.J. and Skidgel,R.A.
  TITLE     Chromosomal localization of the genes for human carboxypeptidase D
            (CPD) and the active 50-kilodalton subunit of human
            carboxypeptidase N (CPN1)
  JOURNAL   Genomics 50 (1), 105-108 (1998)
   PUBMED   9628828
REFERENCE   8  (bases 1 to 9372)
  AUTHORS   Varlamov,O. and Fricker,L.D.
  TITLE     Intracellular trafficking of metallocarboxypeptidase D in AtT-20
            cells: localization to the trans-Golgi network and recycling from
            the cell surface
  JOURNAL   J Cell Sci 111 (Pt 7), 877-885 (1998)
   PUBMED   9490632
REFERENCE   9  (bases 1 to 9372)
  AUTHORS   Tan,F., Rehli,M., Krause,S.W. and Skidgel,R.A.
  TITLE     Sequence of human carboxypeptidase D reveals it to be a member of
            the regulatory carboxypeptidase family with three tandem active
            site domains
  JOURNAL   Biochem J 327 (Pt 1) (Pt 1), 81-87 (1997)
   PUBMED   9355738
REFERENCE   10 (bases 1 to 9372)
  AUTHORS   McGwire,G.B., Tan,F., Michel,B., Rehli,M. and Skidgel,R.A.
  TITLE     Identification of a membrane-bound carboxypeptidase as the
            mammalian homolog of duck gp180, a hepatitis B virus-binding
            protein
  JOURNAL   Life Sci 60 (10), 715-724 (1997)
   PUBMED   9064476
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC090685.8, BC045624.1,
            AC006050.2 and CA436219.1.
            
            On Nov 23, 2018 this sequence version replaced NM_001304.4.
            
            Summary: The metallocarboxypeptidase family of enzymes is divided
            into 2 subfamilies based on sequence similarities. The pancreatic
            carboxypeptidase-like and the regulatory B-type carboxypeptidase
            subfamilies. Carboxypeptidase D has been identified as a regulatory
            B-type carboxypeptidase. CPD is a homolog of duck gp180, a
            hepatitis B virus-binding protein. Transcript variants utilizing
            alternative polyadenylation signals exist for this gene. [provided
            by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer protein (isoform 1).
            
            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 :: SRR1660809.253032.1,
                                           SRR1660809.117995.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000225719.9/ ENSP00000225719.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-26                AC090685.8         110699-110724
            27-4334             BC045624.1         4-4311
            4335-8890           AC006050.2         105035-109590
            8891-9040           CA436219.1         18-167              c
            9041-9372           AC006050.2         109741-110072
FEATURES             Location/Qualifiers
     source          1..9372
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17q11.2"
     gene            1..9372
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /note="carboxypeptidase D"
                     /db_xref="GeneID:1362"
                     /db_xref="HGNC:HGNC:2301"
                     /db_xref="MIM:603102"
     exon            1..800
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     CDS             55..4197
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /EC_number="3.4.17.22"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; metallocarboxypeptidase D"
                     /codon_start=1
                     /product="carboxypeptidase D isoform 1 precursor"
                     /protein_id="NP_001295.2"
                     /db_xref="CCDS:CCDS11257.1"
                     /db_xref="GeneID:1362"
                     /db_xref="HGNC:HGNC:2301"
                     /db_xref="MIM:603102"
                     /translation="MASGRDERPPWRLGRLLLLMCLLLLGSSARAAHIKKAEATTTTT
                     SAGAEAAEGQFDRYYHEEELESALREAAAAGLPGLARLFSIGRSVEGRPLWVLRLTAG
                     LGSLIPEGDAGPDAAGPDAAGPLLPGRPQVKLVGNMHGDETVSRQVLIYLARELAAGY
                     RRGDPRLVRLLNTTDVYLLPSLNPDGFERAREGDCGFGDGGPSGASGRDNSRGRDLNR
                     SFPDQFSTGEPPALDEVPEVRALIEWIRRNKFVLSGNLHGGSVVASYPFDDSPEHKAT
                     GIYSKTSDDEVFKYLAKAYASNHPIMKTGEPHCPGDEDETFKDGITNGAHWYDVEGGM
                     QDYNYVWANCFEITLELSCCKYPPASQLRQEWENNRESLITLIEKVHIGVKGFVKDSI
                     TGSGLENATISVAGINHNITTGRFGDFYRLLVPGTYNLTVVLTGYMPLTVTNVVVKEG
                     PATEVDFSLRPTVTSVIPDTTEAVSTASTVAIPNILSGTSSSYQPIQPKDFHHHHFPD
                     MEIFLRRFANEYPNITRLYSLGKSVESRELYVMEISDNPGVHEPGEPEFKYIGNMHGN
                     EVVGRELLLNLIEYLCKNFGTDPEVTDLVHNTRIHLMPSMNPDGYEKSQEGDSISVIG
                     RNNSNNFDLNRNFPDQFVQITDPTQPETIAVMSWMKSYPFVLSANLHGGSLVVNYPFD
                     DDEQGLATYSKSPDDAVFQQIALSYSKENSQMFQGRPCKNMYPNEYFPHGITNGASWY
                     NVPGGMQDWNYLQTNCFEVTIELGCVKYPLEKELPNFWEQNRRSLIQFMKQVHQGVRG
                     FVLDATDGRGILNATISVAEINHPVTTYKTGDYWRLLVPGTYKITASARGYNPVTKNV
                     TVKSEGAIQVNFTLVRSSTDSNNESKKGKGASSSTNDASDPTTKEFETLIKDLSAENG
                     LESLMLRSSSNLALALYRYHSYKDLSEFLRGLVMNYPHITNLTNLGQSTEYRHIWSLE
                     ISNKPNVSEPEEPKIRFVAGIHGNAPVGTELLLALAEFLCLNYKKNPAVTQLVDRTRI
                     VIVPSLNPDGRERAQEKDCTSKIGQTNARGKDLDTDFTNNASQPETKAIIENLIQKQD
                     FSLSVALDGGSMLVTYPYDKPVQTVENKETLKHLASLYANNHPSMHMGQPSCPNKSDE
                     NIPGGVMRGAEWHSHLGSMKDYSVTYGHCPEITVYTSCCYFPSAARLPSLWADNKRSL
                     LSMLVEVHKGVHGFVKDKTGKPISKAVIVLNEGIKVQTKEGGYFHVLLAPGVHNIIAI
                     ADGYQQQHSQVFVHHDAASSVVIVFDTDNRIFGLPRELVVTVSGATMSALILTACIIW
                     CICSIKSNRHKDGFHRLRQHHDEYEDEIRMMSTGSKKSLLSHEFQDETDTEEETLYSS
                     KH"
     exon            801..1048
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            1049..1191
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            1192..1361
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            1362..1711
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            1712..1903
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            1904..2071
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            2072..2181
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            2182..2284
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            2285..2427
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            2428..2597
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            2598..2927
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            2928..3123
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            3124..3259
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            3260..3391
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            3392..3487
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            3488..3552
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            3553..3684
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            3685..3870
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            3871..3970
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     exon            3971..9372
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /inference="alignment:Splign:2.1.0"
     regulatory      8044..8049
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /note="hexamer: TATAAA"
     polyA_site      8062
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /note="major polyA site"
     regulatory      8662..8667
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /note="hexamer: AATAAA"
     polyA_site      8688
                     /gene="CPD"
                     /gene_synonym="GP180"
     regulatory      9020..9025
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /note="hexamer: AATAAA"
     polyA_site      9040
                     /gene="CPD"
                     /gene_synonym="GP180"
     regulatory      9074..9079
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /note="hexamer: AGTAAA"
     polyA_site      9095
                     /gene="CPD"
                     /gene_synonym="GP180"
     regulatory      9349..9354
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CPD"
                     /gene_synonym="GP180"
                     /note="hexamer: ATTAAA"
     polyA_site      9372
                     /gene="CPD"
                     /gene_synonym="GP180"
ORIGIN      
        1 gcccggagcg ctgagccgcg ggagcggagc cggggttagc ggcgctgctg gaagatggcg
       61 agcggccggg acgagcggcc gccttggcgg ctagggcggc tcctgttgct catgtgcctg
      121 ctgctgctgg ggagctcggc ccgggcggct cacatcaaga aggcggaggc gactaccaca
      181 actacgagcg cgggcgccga ggcggccgag ggccagttcg accgctacta ccacgaagag
      241 gagttggagt cggcgctgag ggaggcggcg gccgcgggcc tccccggcct ggcccgcctc
      301 tttagcatcg gccgctcggt ggaaggccgg ccgctgtggg tgcttcgcct caccgccggc
      361 ctggggtcgc taatccctga gggcgacgcg gggcctgacg ctgccgggcc cgacgctgcg
      421 gggccgctgc tgcccggccg gccccaggtg aagctggtgg gcaacatgca tggcgacgag
      481 accgtgtcgc gccaggtgtt gatctacttg gcccgcgagc tggcggccgg ctaccgccgc
      541 ggggacccgc gcctggtccg cctgctcaac accaccgacg tgtacctgct gcccagcctc
      601 aaccccgatg gcttcgagcg tgcccgcgag ggcgactgtg gcttcggcga cggcggcccg
      661 tccggggcca gcggccgcga caatagtcgc ggccgcgacc tcaaccgaag ctttcccgac
      721 cagtttagca ccggcgaacc ccccgccctg gacgaggtgc ccgaggtgcg cgccctcatc
      781 gagtggatcc gcaggaacaa gtttgtgctt tctggaaatc tgcatggtgg ctcagtggta
      841 gcaagctatc cttttgatga ttctccagaa cataaggcca ctggaatcta tagcaaaacc
      901 tcagatgatg aagtatttaa atacttggca aaagcttatg cttcaaacca ccccataatg
      961 aaaactggtg agcctcattg tccaggagat gaagacgaga ctttcaaaga tggaatcaca
     1021 aacggcgcac attggtatga tgtggaaggt ggtatgcaag attacaatta tgtgtgggcc
     1081 aactgttttg agatcacatt agaactgtct tgttgcaagt acccacctgc ttcacagctt
     1141 cgacaggaat gggagaacaa tcgtgagtct ttgatcacat tgattgaaaa ggttcacatt
     1201 ggagtgaaag gatttgttaa agattccata acaggatctg ggttagagaa tgcaaccatc
     1261 tcagtggctg gtattaatca taatatcaca acaggcagat ttggtgattt ctaccgatta
     1321 cttgttcctg gaacttacaa ccttacagta gttttaactg ggtatatgcc attgactgtt
     1381 actaatgtag tggtgaaaga aggaccagcc acagaggtgg atttttctct taggccaact
     1441 gtaacttcag taatccctga cacgacagag gctgtatcaa ctgctagcac agttgctata
     1501 cctaatattc tttctggaac atcatcctcc taccagccaa ttcagccaaa ggactttcac
     1561 caccaccatt tccctgatat ggaaatcttc ttgagaaggt ttgccaatga atatcctaac
     1621 attacccggc tttattcctt gggaaaatca gtagagtcaa gagaacttta tgtgatggag
     1681 atatctgata atccgggtgt ccatgaacca ggtgaaccag aatttaagta cattggaaat
     1741 atgcatggaa atgaagtggt tggaagagaa ctgctgttga acctcataga atacctttgt
     1801 aagaactttg gaacagaccc tgaagtcaca gatttggttc ataacactag aattcacctt
     1861 atgccatcca tgaatcctga tgggtatgaa aagtcccagg aaggagattc aataagtgta
     1921 attggcagaa acaacagcaa caactttgac ctgaaccgaa atttcccaga ccagtttgtt
     1981 cagatcacag atcctacgca accagaaact attgctgtaa tgagctggat gaagtcctat
     2041 ccatttgtac tttcagcaaa cctgcatgga ggttctttgg tggttaacta cccttttgat
     2101 gatgatgaac aaggacttgc cacatatagt aaatcaccag atgatgctgt gttccaacaa
     2161 atagcacttt cttattccaa ggaaaattcc cagatgtttc aaggtagacc ttgcaagaat
     2221 atgtatccta atgaatattt tcctcatgga ataacaaatg gagctagttg gtataatgtg
     2281 ccaggaggaa tgcaggactg gaactattta caaacaaatt gctttgaagt gactattgaa
     2341 ctaggttgtg tgaaatatcc acttgagaaa gagctgccaa acttttggga acagaatcga
     2401 agatcactaa tccagtttat gaaacaggtt catcagggcg tcagaggatt tgttctagat
     2461 gccacagatg gcaggggtat attaaatgcc accattagtg ttgctgagat taatcaccca
     2521 gtgactactt acaaaactgg agattactgg cgtctcttgg ttccaggaac ttataaaatc
     2581 acagcatctg ctcgagggta taatccagtt accaagaatg tgactgtcaa gagtgaaggc
     2641 gctattcagg tcaacttcac acttgttcga tcctcaacag attcaaacaa tgaatcaaag
     2701 aaaggaaaag gggctagcag cagcaccaat gatgccagtg atccaactac taaagagttt
     2761 gaaactttaa ttaaagacct ttcagcggag aatggtttgg aaagcctcat gttacgctcc
     2821 tcctcaaatc tggctctggc tctttatcga taccattcct acaaagactt atcagagttt
     2881 ctgagaggac ttgtaatgaa ctatccacat attacaaatc ttaccaattt gggacagagc
     2941 actgaatatc gtcacatttg gtcccttgaa atctccaata agcccaatgt atctgagcct
     3001 gaagaaccaa agattcgttt tgttgctggt atccatggaa atgcgccagt tggaactgaa
     3061 ctgcttttgg ctctggcaga atttctctgc ctgaactaca aaaagaaccc agctgttacc
     3121 caattggttg acaggactag gattgtgatt gtcccttctc taaatccaga tgggcgagag
     3181 agagctcaag agaaagactg tacttcaaaa ataggacaaa caaatgctcg tggcaaagat
     3241 ttggatacag acttcacaaa taatgcctcc caacctgaga ccaaagccat cattgaaaat
     3301 ttgattcaaa aacaggactt tagtctttct gttgccttag atggtggttc catgctggtc
     3361 acatatcctt atgacaagcc agtacagaca gtggaaaata aagagactct gaagcatttg
     3421 gcatctcttt atgcaaataa tcatccatcc atgcacatgg gtcagcccag ttgcccaaat
     3481 aaatcagatg agaatattcc aggaggagta atgcgtggag cagaatggca tagtcacctg
     3541 ggcagcatga aggattatag tgtcacctat ggccattgtc cggaaatcac agtatacaca
     3601 agctgctgtt actttcctag tgctgcacga ctcccttcct tgtgggcaga caataagaga
     3661 tctcttctta gtatgttagt ggaggttcac aagggagttc atggatttgt taaagataag
     3721 actggaaagc caatctctaa agcagtcatt gtacttaatg aaggaataaa ggtacaaaca
     3781 aaagagggag gttatttcca tgtactctta gcgccaggtg tccataacat tattgccatc
     3841 gctgatgggt accagcaaca acattcacag gtctttgtgc atcatgatgc agctagttct
     3901 gtggtgatag tctttgacac agataaccgg atatttggtt tgccaaggga gcttgtggta
     3961 actgtatcag gtgctactat gtcggcattg atcctaacag cttgcattat ttggtgcatc
     4021 tgctcaatca agtctaatag acacaaggat ggctttcatc ggctcaggca gcatcatgat
     4081 gagtatgaag atgaaattcg catgatgtct accggctcca agaagtccct cctaagccat
     4141 gagttccagg atgaaacaga cactgaagag gaaacattat attctagcaa acattgaaaa
     4201 acacattttg catatctccc agcataagta ccaagcaaaa ttacagttcc tcttgggaga
     4261 acactgcatt aagaagagag actctcttgc ttcttcaaag agctttggga aattaaattg
     4321 ctaaatttgt attctctgtg aatttcactg gcagttttga acttcccttc cttaaagtac
     4381 tctaaacctt taaaaaaaaa tctgatttat gcagcagaga tgggacagcc actttttctt
     4441 tttaatttaa gatgagctat ttggagctta tgtaataatg gcataaagcc aactagagga
     4501 tgttgtattt tgcacatcag atgtttacta gtggctttag tatttttctt tgttttaaat
     4561 ggccaaaaga atccagaaac attaaggcag ggacagcagt cagaatcgac ataaagcttt
     4621 aaaaactcaa ggttttttca acctactgag gagtactttt ctctagttgt taaatagctg
     4681 gagtttttct tattcaggtt taatggaggt tgaattgatt tttaaacaca tataacagta
     4741 ggaaatgaat aaatgggctt ctgcatttgg ctttctacct gttccaaggc tagatcggaa
     4801 ctggtagact acgctgtaag caggatttca ctacctctct taaggtttag caaacttcta
     4861 aatagcccat tttaagggag aacttactaa ctttattgtg aaaggtctaa atgcccactt
     4921 gaatgaagct gagagagaga tctagcaaaa gctaaaactc atgttgtcta tctttgaact
     4981 tggtaaaaac ccacaggtgc tgctgcttat atctgtgaag cactagctta ttctaggaat
     5041 gcctgattct ttaatattgc ctaaatcgga acctttttct atgttgcaca catggttttc
     5101 agatgaccca gccatctaca agatctgaat tctactgaaa atatctagaa atgtggaaga
     5161 gacctacttg cacattctta acctgtattt gaacacaaaa tatctatact tcatgctcca
     5221 gcccaagcct ataccctgta atagcatact attattgaaa tcgcttgacc ggtcttgttc
     5281 acataggcct ctgggagtga tttggttctt tgccctaatg tttcatttga cggtctcttt
     5341 ttgatcaacc aatttttcta aaagttcagt cgaaagcttt taagtatagc ttcctccctt
     5401 gaaaaaaaat gtaaactatg actgctgagt gataaaacac tgtggtgtga aagtgtcatc
     5461 ttcactgcca atcaggcaaa gaccggaaag atttgcattt tattatgtct gtcttatcat
     5521 gcaatggaaa tgatgctttt tgtaagtatg catcttacca atgatgtaac ggtttaatac
     5581 ctttgaatgt tttaataacc aagttgctgc tgaacttata ctaaatcagg ggaccaaaaa
     5641 acttgctctt atcttctcaa attgtattct atatccatta atgtatcagt tatcccaaag
     5701 ccttcaggtg gaggggttta ccaccttcct aggtcgttca accaggtttt gtgaggaatg
     5761 cattcaaagt ggctttataa aagaagattt tctttagcaa gaataatgag gtcatgtcat
     5821 ttgttaataa gtatctgtga taaatccgtg gttcaaggtt aagccattct ggtattctgg
     5881 tattagcaac tgtaaattct gccacctcat acatggaaca gagcttgtgg gatgctaata
     5941 gttagtgaag tatacatgat ttaatttcta ataatcttta tgttttcttt aaggatggtg
     6001 gtgtattgct ctttttcagc tttattttta agagtacagt caggaaacca acaaggggcc
     6061 taagagtggc tgcccctgct tgggacatta cagcaagtga aacaaagtta atgtgacaag
     6121 ctttgctttg ttatcattgg tcttcactag aggatacctt ttacatgtac ttctctcttg
     6181 gatcaaatat gtctttaact gtacatctca gtggctggag gccatgcctt ttaagcatgt
     6241 gtaaaatttt taaagaaatg aacatacaca tagttatttt agtaatattt cctgaaagaa
     6301 aaaccaaatt ctgctataag tcttgatctt caatgaactt ttaaataatg catttagctg
     6361 gaaaacaaga ctttcccagc ttgtattacc tagaagcgtg aatgtatagg atacctgact
     6421 actaagacta tattctcagc cctgccctgt cttttatttg cgggtctaat ctaatattag
     6481 aatatattaa ccgcttaagg cattgaagcc atatgggatg gggaatgcat ttcttcagtg
     6541 tttctccgag agactttcca tttccttgga gttatggcgg caagtaagta tcatagtatt
     6601 aagaaatttg cctaaatctg agttgtgcct ttctttactc acaaggcatg ggctttgtcc
     6661 tggtgatcag tttgtaagcc ttcttccttc ccagctcctt aataaaagca aagtgattga
     6721 gtaggtaatg ttcaaagtgt ctgcctgtgt acatgtactt gtattgatta tgtagttcag
     6781 taagatgtgc ccaagtcatt tcagaaagaa agacccttca gttttgatgc attttgctga
     6841 acacttgggt agtgagtggg atcctatcca gttgaggaat gcttgcaatg ctcattgaag
     6901 ggatttgctt tgggactttg tcatcttcca gaaaggaaac atattgtata tttggcccag
     6961 tgtgattgat tgctttatct ttggtaactt ttacttgaat gggatttgct gaattaatga
     7021 ctattgaatt taaaactaat tatgagttga caaataaata aaaggtagtg tttatgtctg
     7081 agcttattgt gtttgagcta acaccaggtt actcagtaac catgacctgc tcctccattt
     7141 ccatttattc tcaacattaa atagttttat cttgttgttg ccagaaatgc acttgtgcca
     7201 ggtattgtcc ctgctgtatg aaaagcttct tggcaatgaa ttctgtaata gtgccctaca
     7261 ttatggtttt ctggtggaat tgttttaaca gtgacaaccc aggatttcca atatattttt
     7321 gttttattgt tattaccaaa aattccacta tgattgatgt tcagtgattt tctatagcaa
     7381 cttttttggt aactctttgg gtttctgatt tgttttagct aaaattttgg ggatatgatt
     7441 tgggtctttg attaatgtca gctgaacttg gatttctagt tcatgaagaa atctctccca
     7501 atacccattt atcctatttt tagcaataat tcgttaatga ttccacttga ttttcagaat
     7561 attgtcctgg ttgattttga tttgacagca tacattatga aatttgaaag taggttacca
     7621 ttttgaggca gttggatata aattatgtaa atatgtatga ttatgatttt tataaatggc
     7681 ataacatgag tgtactaact accttctatg ctggccatgc tacagatttt ctggaggtat
     7741 gacaatagta tttttttatg ctcagattaa aaatcagctt ttcacctctc cagtttttcc
     7801 aagtgatact cccagttcta gagcaatcta cagctgttta tgtgaggtgc ccaacaccca
     7861 ttcatctcaa gtgcttcagt ctttggttta tttcatgcac tgtgccttca aaatgaaatt
     7921 tttaaaaggg actttaaatg aagttgaata gtagttttta aaagtcaatt tgtaatttat
     7981 gtgaaatcta actgtaatga ggtcctttct gttttttata tgtaaacaga tctactaatc
     8041 ctgtataaaa gttattttac gatgtttgtc tttctttgtg ttttgtctca taatcttttt
     8101 tcagatgcaa tatgccggaa aaagttatag gtccagtttg aaaattattt agtttttctg
     8161 cctatgctag tggaaaaata gtaccaggat cagaatacag ggtatcacct atggaatgtt
     8221 tctgtattta tgaattgact caaaagaaag ctttgtttct gaaatcgcat tatgtagtag
     8281 ccacagtttt ctgtttgtag ctcagctaga ttgttatata tgttcaatca tttcacaata
     8341 acaacacaaa actggtcatt gaaaggtttt tatgtacgca ttttaaactt gttcgttaaa
     8401 aatttggtcc tttttccagg tgaggcccag ttagaataat gtgtcccggc acttttaggc
     8461 acagcaagga tgaattcaat atcccctttt cacttagcaa caatgtgtta cttctaccct
     8521 aataggaatt gggaaagcaa agttgtatga gaaacagact ctgctgataa agtactcata
     8581 gtccagacca gagaaatata aatggaaata ggttatattt caatagtgat tggttcatct
     8641 aaaagtctct gctgtaaagg aaataaagca tagaggtttg agcatggact ttggagttgg
     8701 accaatctgt gactgattct tcgttctgct acttgcttcc aatgtgacct tgtacaagtt
     8761 tcttgacatt ctctgagcct cagtttctct actggttgaa taatccttga taggattgca
     8821 gtggaaaatt aaatgaaata atgttagcaa aggtcccaac ataatatttg acttggaatt
     8881 gaatgcccat ggtaaccagc atcattttcc ttcatgtgat gtcttcttat gcctttgaaa
     8941 gaaagttact ttatcaaatg tataaataaa gatctgttta taggtgatct ttttaattta
     9001 gaagaaattc tgagacacaa ataaaaaaag aaatttttta ttatgtggtt caatagattg
     9061 tctaaagcat ggcagtaaag ttttaattat gccaagatgc ttcatatttg tttttaaatg
     9121 aaattaagtt gtatttatgc ttctttagtg aaaacaacgt tacttaactg ctacaggaag
     9181 tgtgaatagt gataacagtt ctttttctct cagtgtttga aatattttcc tgaattttct
     9241 tagttttctc atacctgaat caagaaccct tttggtttgt ttcataaaca gtaatctagt
     9301 tattatgttc agcttttcag atttataata gctgattgtt ctcagcaaat taaacatgat
     9361 ggtcaacgct aa
//
