LOCUS       NM_001372043           10226 bp    mRNA    linear   PRI 10-FEB-2025
DEFINITION  Homo sapiens proprotein convertase subtilisin/kexin type 5 (PCSK5),
            transcript variant 4, mRNA.
ACCESSION   NM_001372043 XM_005252039
VERSION     NM_001372043.1
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 10226)
  AUTHORS   Wang,J., Sun,Y., Chen,R., Meng,D., Wei,Y., Jiang,L. and Kong,X.
  TITLE     Pro-fibrotic effect of the susceptible gene PCSK5 in vascular
            fibrosis of Takayasu arteritis via TGF-beta and SMAD3 signaling
            pathway activation
  JOURNAL   J Autoimmun 148, 103277 (2024)
   PUBMED   38972101
  REMARK    GeneRIF: Pro-fibrotic effect of the susceptible gene PCSK5 in
            vascular fibrosis of Takayasu arteritis via TGF-beta and SMAD3
            signaling pathway activation.
REFERENCE   2  (bases 1 to 10226)
  AUTHORS   Petra,E., Siwy,J., Vlahou,A. and Jankowski,J.
  TITLE     Urine peptidome in combination with transcriptomics analysis
            highlights MMP7, MMP14 and PCSK5 for further investigation in
            chronic kidney disease
  JOURNAL   PLoS One 17 (1), e0262667 (2022)
   PUBMED   35045102
  REMARK    GeneRIF: Urine peptidome in combination with transcriptomics
            analysis highlights MMP7, MMP14 and PCSK5 for further investigation
            in chronic kidney disease.
            Erratum:[PLoS One. 2024 Jun 13;19(6):e0305767. doi:
            10.1371/journal.pone.0305767.. PMID: 38870254]
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 10226)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   4  (bases 1 to 10226)
  AUTHORS   Hoac,B., Susan-Resiga,D., Essalmani,R., Marcinkiweicz,E.,
            Seidah,N.G. and McKee,M.D.
  TITLE     Osteopontin as a novel substrate for the proprotein convertase 5/6
            (PCSK5) in bone
  JOURNAL   Bone 107, 45-55 (2018)
   PUBMED   29126984
  REMARK    GeneRIF: this study demonstrates that Pcsk5 is expressed in
            bone-forming cells, and that OPN is a novel substrate for PC5/6
REFERENCE   5  (bases 1 to 10226)
  AUTHORS   Mercure,C., Jutras,I., Day,R., Seidah,N.G. and Reudelhuber,T.L.
  TITLE     Prohormone convertase PC5 is a candidate processing enzyme for
            prorenin in the human adrenal cortex
  JOURNAL   Hypertension 28 (5), 840-846 (1996)
   PUBMED   8901832
REFERENCE   6  (bases 1 to 10226)
  AUTHORS   Nachtigal,M.W. and Ingraham,H.A.
  TITLE     Bioactivation of Mullerian inhibiting substance during gonadal
            development by a kex2/subtilisin-like endoprotease
  JOURNAL   Proc Natl Acad Sci U S A 93 (15), 7711-7716 (1996)
   PUBMED   8755541
REFERENCE   7  (bases 1 to 10226)
  AUTHORS   Miranda,L., Wolf,J., Pichuantes,S., Duke,R. and Franzusoff,A.
  TITLE     Isolation of the human PC6 gene encoding the putative host protease
            for HIV-1 gp160 processing in CD4+ T lymphocytes
  JOURNAL   Proc Natl Acad Sci U S A 93 (15), 7695-7700 (1996)
   PUBMED   8755538
REFERENCE   8  (bases 1 to 10226)
  AUTHORS   Campan,M., Yoshizumi,M., Seidah,N.G., Lee,M.E., Bianchi,C. and
            Haber,E.
  TITLE     Increased proteolytic processing of protein tyrosine phosphatase mu
            in confluent vascular endothelial cells: the role of PC5, a member
            of the subtilisin family
  JOURNAL   Biochemistry 35 (12), 3797-3802 (1996)
   PUBMED   8620001
REFERENCE   9  (bases 1 to 10226)
  AUTHORS   Seidah,N.G., Benjannet,S., Pareek,S., Savaria,D., Hamelin,J.,
            Goulet,B., Laliberte,J., Lazure,C., Chretien,M. and Murphy,R.A.
  TITLE     Cellular processing of the nerve growth factor precursor by the
            mammalian pro-protein convertases
  JOURNAL   Biochem J 314 (Pt 3) (Pt 3), 951-960 (1996)
   PUBMED   8615794
REFERENCE   10 (bases 1 to 10226)
  AUTHORS   Mbikay,M., Seidah,N.G., Chretien,M. and Simpson,E.M.
  TITLE     Chromosomal assignment of the genes for proprotein convertases PC4,
            PC5, and PACE 4 in mouse and human
  JOURNAL   Genomics 26 (1), 123-129 (1995)
   PUBMED   7782070
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL359253.17, AL353607.20,
            AL589653.9 and AL391868.16.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Aug 2, 2019 this sequence version replaced XM_005252039.4.
            
            Summary: This gene encodes a member of the subtilisin-like
            proprotein convertase family, which includes proteases that process
            protein and peptide precursors trafficking through regulated or
            constitutive branches of the secretory pathway. The encoded protein
            undergoes an initial autocatalytic processing event in the ER to
            generate a heterodimer which exits the ER. It then sorts to the
            trans-Golgi network where a second autocatalytic event takes place
            and the catalytic activity is acquired. This encoded protein is
            widely expressed and one of the seven basic amino acid-specific
            members which cleave their substrates at single or paired basic
            residues. It mediates posttranslational endoproteolytic processing
            for several integrin alpha subunits and is thought to process
            prorenin, pro-membrane type-1 matrix metalloproteinase and HIV-1
            glycoprotein gp160. Alternative splicing results in multiple
            transcript variants, some of which encode distinct isoforms,
            including a protease packaged into dense core granules (PC5A) and a
            type 1 membrane bound protease (PC5B). [provided by RefSeq, May
            2014].
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR14372079.1105604.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA2142348
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000674117.1/ ENSP00000500971.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-701               AL359253.17        13826-14526
            702-806             AL359253.17        55532-55636
            807-920             AL359253.17        109285-109398
            921-1064            AL359253.17        146891-147034
            1065-1141           AL359253.17        150114-150190
            1142-1230           AL353607.20        3500-3588
            1231-1403           AL353607.20        7271-7443
            1404-1616           AL353607.20        31435-31647
            1617-1717           AL353607.20        42796-42896
            1718-1821           AL353607.20        69654-69757
            1822-1939           AL353607.20        92590-92707
            1940-2128           AL353607.20        94528-94716
            2129-2265           AL353607.20        105249-105385
            2266-2409           AL353607.20        110531-110674
            2410-2512           AL353607.20        115141-115243
            2513-2706           AL353607.20        116943-117136
            2707-2791           AL353607.20        120218-120302
            2792-2889           AL353607.20        124123-124220
            2890-3019           AL353607.20        124639-124768
            3020-3135           AL353607.20        125176-125291
            3136-3238           AL589653.9         23878-23980
            3239-3375           AL589653.9         29835-29971
            3376-3582           AL589653.9         35334-35540
            3583-3651           AL589653.9         36991-37059
            3652-3694           AL589653.9         88608-88650
            3695-3831           AL589653.9         91650-91786
            3832-4032           AL589653.9         93040-93240
            4033-4113           AL589653.9         98512-98592
            4114-4197           AL589653.9         105020-105103
            4198-4393           AL391868.16        3732-3927
            4394-4611           AL391868.16        14498-14715
            4612-4848           AL391868.16        16128-16364
            4849-5079           AL391868.16        21085-21315
            5080-5257           AL391868.16        25509-25686
            5258-5475           AL391868.16        31306-31523
            5476-5576           AL391868.16        43904-44004
            5577-5763           AL391868.16        47109-47295
            5764-10226          AL391868.16        51589-56051
FEATURES             Location/Qualifiers
     source          1..10226
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="9"
                     /map="9q21.13"
     gene            1..10226
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /note="proprotein convertase subtilisin/kexin type 5"
                     /db_xref="GeneID:5125"
                     /db_xref="HGNC:HGNC:8747"
                     /db_xref="MIM:600488"
     exon            1..701
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     CDS             510..6173
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /EC_number="3.4.21.-"
                     /note="isoform 3 precursor is encoded by transcript
                     variant 4; protease PC6; prohormone convertase 5;
                     subtilisin/kexin-like protease PC5; proprotein convertase
                     6; subtilase"
                     /codon_start=1
                     /product="proprotein convertase subtilisin/kexin type 5
                     isoform 3 precursor"
                     /protein_id="NP_001358972.1"
                     /db_xref="CCDS:CCDS94423.1"
                     /db_xref="GeneID:5125"
                     /db_xref="HGNC:HGNC:8747"
                     /db_xref="MIM:600488"
                     /translation="MGWGSRCCCPGRLDLLCVLALLGGCLLPVCRTRVYTNHWAVKIA
                     GGFPEANRIASKYGFINIGQIGALKDYYHFYHSRTIKRSVISSRGTHSFISMEPKVEW
                     IQQQVVKKRTKRDYDFSRAQSTYFNDPKWPSMWYMHCSDNTHPCQSDMNIEGAWKRGY
                     TGKNIVVTILDDGIERTHPDLMQNYDALASCDVNGNDLDPMPRYDASNENKHGTRCAG
                     EVAAAANNSHCTVGIAFNAKIGGVRMLDGDVTDMVEAKSVSFNPQHVHIYSASWGPDD
                     DGKTVDGPAPLTRQAFENGVRMGRRGLGSVFVWASGNGGRSKDHCSCDGYTNSIYTIS
                     ISSTAESGKKPWYLEECSSTLATTYSSGESYDKKIITTDLRQRCTDNHTGTSASAPMA
                     AGIIALALEANPFLTWRDVQHVIVRTSRAGHLNANDWKTNAAGFKVSHLYGFGLMDAE
                     AMVMEAEKWTTVPRQHVCVESTDRQIKTIRPNSAVRSIYKASGCSDNPNRHVNYLEHV
                     VVRITITHPRRGDLAIYLTSPSGTRSQLLANRLFDHSMEGFKNWEFMTIHCWGERAAG
                     DWVLEVYDTPSQLRNFKTPGKLKEWSLVLYGTSVQPYSPTNEFPKVERFRYSRVEDPT
                     DDYGTEDYAGPCDPECSEVGCDGPGPDHCNDCLHYYYKLKNNTRICVSSCPPGHYHAD
                     KKRCRKCAPNCESCFGSHGDQCMSCKYGYFLNEETNSCVTHCPDGSYQDTKKNLCRKC
                     SENCKTCTEFHNCTECRDGLSLQGSRCSVSCEDGRYFNGQDCQPCHRFCATCAGAGAD
                     GCINCTEGYFMEDGRCVQSCSISYYFDHSSENGYKSCKKCDISCLTCNGPGFKNCTSC
                     PSGYLLDLGMCQMGAICKDGEYVDEHGHCQTCEASCAKCQGPTQEDCTTCPMTRIFDD
                     GRCVSNCPSWKFEFENQCHPCHHTCQRCQGSGPTHCTSCGADNYGREHFLYQGECGDS
                     CPEGHYATEGNTCLPCPDNCELCHSVHVCTRCMKGYFIAPTNHTCQKLECGQGEVQDP
                     DYEECVPCEEGCLGCSLDDPGTCTSCAMGYYRFDHHCYKTCPEKTYSEEVECKACDSN
                     CGSCDQNGCYWCEEGFFLLGGSCVRKCGPGFYGDQEMGECESCHRACETCTGPGHDEC
                     SSCQEGLQLLRGMCVHATKTQEEGKFWNEAVSTANLSVVKSLLQERRRWKVQIKRDIL
                     RKLQPCHSSCKTCNGSATLCTSCPKGAYLLAQACVSSCPQGTWPSVRSGSCENCTEAC
                     AICSGADLCKKCQMQPGHPLFLHEGRCYSKCPEGSYAEDGICERCSSPCRTCEGNATN
                     CHSCEGGHVLHHGVCQENCPERHVAVKGVCKHCPEMCQDCIHEKTCKECTPEFFLHDD
                     MCHQSCPRGFYADSRHCVPCHKDCLECSGPKADDCELCLESSWVLYDGLCLEECPAGT
                     YYEKETKECRDCHKSCLTCSSSGTCTTCQKGLIMNPRGSCMANEKCSPSEYWDEDAPG
                     CKPCHVKCFHCMGPAEDQCQTCPMNSLLLNTTCVKDCPEGYYADEDSNRCAHCHSSCR
                     TCEGRHSRQCHSCRPGWFQLGKECLLQCREGYYADNSTGRCERCNRSCKGCQGPRPTD
                     CLSCDRFFFLLRSKGECHRSCPDHYYVEQSTQTCERCHPTCDQCKGKGALNCLSCVWS
                     YHLMGGICTSDCLVGEYRVGEGEKFNCEKCHESCMECKGPGAKNCTLCPANLVLHMDD
                     SHCLHCCNTSDPPSAQECCDCQDTTDECILRTSKVRPATEHFKTALFITSSMMLVLLL
                     GAAVVVWKKSRGRVQPAAKAGYEKLADPNKSYSSYKSSYRESTSFEEDQVIEYRDRDY
                     DEDDDDDIVYMGQDGTVYRKFKYGLLDDDDIDELEYDDESYSYYQ"
     exon            702..806
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            807..920
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            921..1064
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            1065..1141
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            1142..1230
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            1231..1403
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            1404..1616
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            1617..1717
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            1718..1821
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            1822..1939
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            1940..2128
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            2129..2265
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            2266..2409
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            2410..2512
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            2513..2706
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            2707..2791
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            2792..2889
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            2890..3019
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            3020..3135
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            3136..3238
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            3239..3375
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            3376..3582
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            3583..3651
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            3652..3694
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            3695..3831
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            3832..4032
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            4033..4113
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            4114..4197
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            4198..4393
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            4394..4611
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            4612..4848
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            4849..5079
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            5080..5257
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            5258..5475
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            5476..5576
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            5577..5763
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     exon            5764..10226
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /inference="alignment:Splign:2.1.0"
     regulatory      10206..10211
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /note="hexamer: AATAAA"
     polyA_site      10226
                     /gene="PCSK5"
                     /gene_synonym="PC5; PC6; PC6A; SPC6"
                     /note="major polyA site"
ORIGIN      
        1 gccactcaga atcctcgcgc gctgctcgga gccggaggga gcgctgggag cgagcaagcg
       61 agcgtttgga gcccgggcca gcagaggggg cgcccggtcg ctgcctgtac cgctcccgct
      121 ggtcatctcc gccgcgctcg ggggccccgg gaggagcgag accgagtcgg agagtccggg
      181 agccaagccg ggcgaaaccc aactgcggag gacgcccgcc ccactcagcc tcctcctgcg
      241 tccgagccgg ggagcatcgc cgagcgcccc acgggccgga gagctgggag cacaggtccc
      301 ggcagcccca gggatggtct aggagccggc gtaaggctcg ctgctctgct ccctgccggg
      361 gctagccgcc tcctgccgat cgcccggggc tgcgagctgc ggcggcccgg ggctgctcgc
      421 cgggcggcgc aggccggaga agttagttgt gcgcgccctt agtgcgcgga accagccagc
      481 gagcgaggga gcagcgaggc gccgggacca tgggctgggg gagccgctgc tgctgcccgg
      541 gacgtttgga cctgctgtgc gtgctggcgc tgctcggggg ctgcctgctc cccgtgtgtc
      601 ggacgcgcgt ctacaccaac cactgggcag tcaaaatcgc cgggggcttc ccggaggcca
      661 accgtatcgc cagcaagtac ggattcatca acataggaca gataggggcc ctgaaggact
      721 actaccactt ctaccatagc aggacgatta aaaggtcagt tatctcgagc agagggaccc
      781 acagtttcat ttcaatggaa ccaaaggtgg aatggatcca acagcaagtg gtaaaaaagc
      841 ggacaaagag ggattatgac ttcagtcgtg cccagtctac ctatttcaat gatcccaagt
      901 ggcccagcat gtggtatatg cactgcagtg acaatacaca tccctgccag tctgacatga
      961 atatcgaagg agcctggaag agaggctaca cgggaaagaa cattgtggtc actatcctgg
     1021 atgacggaat tgagagaacc catccagatc tgatgcaaaa ctacgatgct ctggcaagtt
     1081 gcgacgtgaa tgggaatgac ttggacccaa tgcctcgtta tgatgcaagc aacgagaaca
     1141 agcatgggac tcgctgtgct ggagaagtgg cagccgctgc aaacaattcg cactgcacag
     1201 tcggaattgc tttcaacgcc aagatcggag gagtgcgaat gctggacgga gatgtcacgg
     1261 acatggttga agcaaaatca gttagcttca acccccagca cgtgcacatt tacagcgcca
     1321 gctggggccc ggatgatgat ggcaagactg tggacggacc agcccccctc acccggcaag
     1381 cctttgaaaa cggcgttaga atggggcgga gaggcctcgg ctctgtgttt gtttgggcat
     1441 ctggaaatgg tggaaggagc aaagaccact gctcctgtga tggctacacc aacagcatct
     1501 acaccatctc catcagcagc actgcagaaa gcggaaagaa accttggtac ctggaagagt
     1561 gttcatccac gctggccaca acctacagca gcggggagtc ctacgataag aaaatcatca
     1621 ctacagatct gaggcagcgt tgcacggaca accacactgg gacgtcagcc tcagccccca
     1681 tggctgcagg catcattgcg ctggccctgg aagccaatcc gtttctgacc tggagagacg
     1741 tacagcatgt tattgtcagg acttcccgtg cgggacattt gaacgctaat gactggaaaa
     1801 ccaatgctgc tggttttaag gtgagccatc tttatggatt tggactgatg gacgcagaag
     1861 ccatggtgat ggaggcagag aagtggacca ccgttccccg gcagcacgtg tgtgtggaga
     1921 gcacagaccg acaaatcaag acaatccgcc ctaacagtgc agtgcgctcc atctacaaag
     1981 cttcaggctg ctcggataac cccaaccgcc atgtcaacta cctggagcac gtcgttgtgc
     2041 gcatcaccat cacccacccc aggagaggag acctggccat ctacctgacc tcgccctctg
     2101 gaactaggtc tcagcttttg gccaacaggc tatttgatca ctccatggaa ggattcaaaa
     2161 actgggagtt catgaccatt cattgctggg gagaaagagc tgctggtgac tgggtccttg
     2221 aagtttatga tactccctct cagctaagga actttaagac tccaggtaaa ttgaaagaat
     2281 ggtctttggt cctctacggc acctccgtgc agccatattc accaaccaat gaatttccga
     2341 aagtggaacg gttccgctat agccgagttg aagaccccac agacgactat ggcacagagg
     2401 attatgcagg tccctgcgac cctgagtgca gtgaggttgg ctgtgacggg ccaggaccag
     2461 accactgcaa tgactgtttg cactactact acaagctgaa aaacaatacc aggatctgtg
     2521 tctccagctg cccccctggc cactaccacg ccgacaagaa gcgctgcagg aagtgtgccc
     2581 ccaactgtga gtcctgcttt gggagccatg gtgaccaatg catgtcctgc aaatatggat
     2641 actttctgaa tgaagaaacc aacagctgtg ttactcactg ccctgatggg tcatatcagg
     2701 ataccaagaa aaatctttgc cggaaatgca gtgaaaactg caagacatgt actgaattcc
     2761 ataactgtac agaatgtagg gatgggttaa gcctgcaggg atcccggtgc tctgtctcct
     2821 gtgaagatgg acggtatttc aacggccagg actgccagcc ctgccaccgc ttctgcgcca
     2881 cttgtgctgg ggcaggagct gatgggtgca ttaactgcac agagggctac ttcatggagg
     2941 atgggagatg cgtgcagagc tgtagtatca gctattactt tgaccactct tcagagaatg
     3001 gatacaaatc ctgcaaaaaa tgtgatatca gttgtttgac gtgcaatggc ccaggattca
     3061 agaactgtac aagctgccct agtgggtatc tcttagactt aggaatgtgt caaatgggag
     3121 ccatttgcaa ggatggagaa tatgttgatg agcatggcca ctgccagacc tgtgaggcct
     3181 catgtgccaa gtgccaggga ccaacccagg aagactgcac tacctgcccc atgacaagga
     3241 tttttgatga tggccgctgt gtttcgaact gcccctcatg gaaatttgaa tttgagaacc
     3301 aatgccatcc atgccaccac acctgccaga gatgccaagg aagtggccct acccactgca
     3361 cctcctgtgg agcagacaac tatggccgag agcacttcct gtaccaggga gagtgtggag
     3421 atagctgccc agagggccac tatgccactg aggggaacac ctgcctgccc tgcccagaca
     3481 actgtgagct ttgccacagc gtgcatgtct gcacaagatg catgaagggc tacttcatag
     3541 cgcccaccaa ccacacatgc cagaagttag agtgtggaca aggtgaagtc caagacccag
     3601 actatgaaga atgtgtccct tgtgaagaag gatgtctggg atgcagcttg gatgatccag
     3661 gaacatgtac atcttgcgct atggggtatt acaggtttga tcaccattgt tataaaacct
     3721 gtcctgagaa gacctacagt gaggaagtgg aatgcaaggc gtgtgatagt aactgtggca
     3781 gctgtgacca gaatgggtgt tactggtgtg aagagggctt ctttctctta ggtggcagtt
     3841 gtgtgaggaa atgtggtcct ggattctatg gtgaccaaga aatgggagaa tgtgagtcct
     3901 gccaccgagc atgcgaaacc tgcacaggcc ctggtcatga cgagtgcagc agctgccagg
     3961 aaggactgca gctgctgcgt gggatgtgcg tgcatgccac caagacccag gaggagggca
     4021 aattctggaa tgaagctgtg tccactgcaa acctatctgt ggtgaagagc ctgctgcagg
     4081 agcgacgaag gtggaaagtt caaatcaaaa gagatatttt gagaaaactc cagccttgtc
     4141 attcttcttg taaaacctgc aatggatctg caactctgtg cacttcatgt cccaaaggtg
     4201 catatcttct ggctcaggcc tgtgtttcct cctgtcccca aggcacatgg ccttccgtaa
     4261 ggagtgggag ctgcgagaac tgtacggagg cctgtgccat ctgctctgga gccgatcttt
     4321 gcaaaaaatg ccagatgcag ccgggccacc ctctcttcct ccatgaaggc aggtgctact
     4381 ccaagtgccc ggagggctct tatgcagaag acggcatatg tgaacgctgt agctctcctt
     4441 gcagaacatg tgaaggaaac gccaccaact gccattcttg tgaaggaggc cacgtcctgc
     4501 accacggagt gtgccaggaa aactgccccg agaggcacgt ggctgtgaag ggggtatgca
     4561 agcattgccc agagatgtgt caggactgca tccatgagaa aacatgcaaa gagtgcacgc
     4621 ctgagttctt cctgcacgat gatatgtgcc accagtcctg tccccgtggc ttctatgcag
     4681 actcgcgcca ctgtgtcccc tgccataaag actgtctgga gtgcagtggc cccaaagccg
     4741 acgactgcga gctctgtctt gagagttcct gggtcctcta tgatggactg tgcttggagg
     4801 agtgtccagc aggaacctat tatgaaaagg agactaagga gtgcagagat tgccacaagt
     4861 cctgcttgac ctgctcatca tctgggacct gcaccacctg tcagaaaggc ctgatcatga
     4921 accctcgtgg gagctgcatg gccaacgaga agtgctcacc ctccgagtac tgggatgagg
     4981 atgctcccgg gtgcaagccc tgccatgtta agtgcttcca ctgcatgggg ccggcggagg
     5041 accagtgtca aacatgcccc atgaacagcc ttcttctcaa cacaacctgt gtgaaggact
     5101 gcccagaggg ctattatgcc gatgaggaca gcaaccggtg tgcccactgc cacagctctt
     5161 gcaggacatg tgaagggaga cacagcaggc agtgccactc ctgccgaccg ggctggttcc
     5221 agctaggaaa agagtgcctg ctccagtgca gggaaggata ttacgcagac aactccactg
     5281 gccggtgtga gaggtgcaac aggagctgca aggggtgcca gggcccacgg cccacagact
     5341 gcctgtcttg cgatagattt ttctttctgc tccgctccaa aggagagtgt catcgctcct
     5401 gcccagacca ttactatgta gagcaaagca cacagacctg tgagagatgc catccgactt
     5461 gtgatcaatg caaaggaaaa ggagcgttga attgtttatc ctgtgtgtgg agttaccacc
     5521 tcatgggagg gatctgcacc tcggactgtc ttgtggggga atacagagtg ggagagggag
     5581 agaagtttaa ctgtgaaaaa tgccacgaga gctgcatgga atgcaaggga ccaggggcca
     5641 agaactgcac cttgtgccct gccaacctgg tgctgcacat ggacgacagc cactgcctcc
     5701 actgctgcaa cacctctgat ccccccagtg cccaggagtg ctgtgactgc caggacacca
     5761 cggacgaatg catccttcga acaagcaagg ttaggcctgc aactgagcat ttcaagacag
     5821 ctctgttcat cacctcctcc atgatgctgg tgcttctgct cggggcagct gtggtagtgt
     5881 ggaagaaatc tcgtggccga gtccagccag cagcaaaggc cggctatgaa aaactggccg
     5941 accccaacaa gtcttactcc tcctataaga gcagctatag agagagcacc agctttgaag
     6001 aggatcaggt gattgagtac agggatcggg actatgatga ggatgatgat gatgacatcg
     6061 tctacatggg ccaggatggc acagtctacc ggaaatttaa atatgggctg ctggatgacg
     6121 atgacataga tgagctggaa tatgatgacg agagttactc ctactaccag taaacaggca
     6181 ctcccccacc aacaccacca ttccactctc aggcatgcct gtgagcatca ctgtttttgg
     6241 ttttatcccc acaccaggct gatgtgtgag tttttctatt tgtcttcttt aaccatgagt
     6301 ccaaccagaa tatgtaagaa tgatgaaata ctttgttctt cttttgagtg gctaaactca
     6361 attaacagtt cctgttcaac cgtaattgaa gagcaaggat aaaattcaga ggcattttcc
     6421 tcaaaataat gtgttaagac acaaaaatga aggaagtgaa aacaaatgag atttgtacaa
     6481 actcttctat gtgattttaa aaaaaggaca gcagatctat agaaattctg tttccgagct
     6541 gcattgtgga ggtgtctgct gcctcctggt attctaattt ttctttatct aattttgggg
     6601 ataatggagg tacaaaggag ttgttggttt ggtggtgttt ttcttccctt tagctgtctt
     6661 taggcagaaa tttgttttgt aagggccaag aaaagagggc tcttatcaat tgactccagg
     6721 ccacccctgg tgagcagaag agaccacctg ggctgggctg ctcaggacct acttgagata
     6781 agggaagaaa agagaaggtg catcatagct gaggagccat gaggtcaccc caggccctag
     6841 ttcctccgca ggaatccaga gtcacaacaa ttctaaaggc agagcaagcc cagcgagaaa
     6901 gaaataactg aatttccagg aactgcactc tcatgatttt ctgggtactt ttcgcctggg
     6961 agacatcagc taagacatcg aataataaaa gaaaaatggc agtgttaacc taacataaaa
     7021 tggaataaaa tgacaaacac ttcatccgct ctaaaaaatt cagagctttc cttcatcaac
     7081 aacccatcac aaaaccgtgg actctcaata gaaagagttg gaatagagtc taacatggaa
     7141 aaaaaaaaat cccaatatgc tgctcacaag ctgtactcta gctgctgacc agccttccag
     7201 cactgctcat cactatgatt tttgtttcta gacttcctag gcttcctttt ttccattctt
     7261 ctgtcaagtg tattcttgga ttcatgcaac tgaggacagt ttttgtccag attgtaacac
     7321 agagaagggc tcttgctatg caaaatgatg ttggcagggt cttacagatt tccttgtcaa
     7381 aatagacctt acaggcagta ctagaaatgg agcaccagaa agcaaaaatg acattttcag
     7441 agaatgatga taattataat ctattgcaca cctactacca gataacaagc taagtaattc
     7501 ccccccaaaa atgccccact tatccatttt ggtacttacc atactcccat gaggttggta
     7561 ttgctattat tctgttcttg taggaaacct gaggcttaca agaggttagg taactagtcc
     7621 aaggtcatgc aaagctcaac aaaattcaag aaaaaagaat gatcacccta aagcgtgtgt
     7681 tcttataact atgctactga aataaggtgg gaaaataagc atcctaaata taattaaagt
     7741 catgcctatt gttttagtct ataatatcaa tgttatcttt actaaattca tggattttct
     7801 ttttttaaca taatgtatca ctgacacaga aaatctttat gaagaagtct tcagtttact
     7861 aaaggcttgt gcttctttag aggaaagctc ttaaaacagg gttgacaaac agtctctgga
     7921 aagagccagc tagtaagtac attaggcttt cttggccaga aagtctctgt cataaccact
     7981 cagctctgct attatagcat gaatgcagct ggtacataac ggatgggtga gctgtgcttc
     8041 aataaaacct tatttatgga cactgacatt tgaaattcag gtaattttca catattataa
     8101 aattttattc ttcttttgat ttttttcaac cttttaaaat ttaaaaatgc aaaagctatt
     8161 ctcagttcac agcattacaa gaacaggtgg tgggtcagat ttggccaaca ggctgtactt
     8221 tgctgacttt atctttaaaa cagttttcag agatcataca tgtacatgta tgatatgcct
     8281 ccaaaaattt tgatcattta aaattatctc cttggccagg cgtggtggct catacctcta
     8341 atcctagcac tttgggagac tgaggcaggc agatcacctg aagtcaggag tttgatacca
     8401 gcttagccaa catggtgaaa ccccatttct actaaaaata caataaaaat ctgggcatgt
     8461 tggtgcacac ctgtaatccc agctactcag gaggctgagg caggcaaatc acttgagccc
     8521 gggaggcaga ggttgcagtg agcggagatg gcaccattgc actccagcct gggtgacaga
     8581 gcaagactcc atctcaaaaa ataagtaact aactaactaa ctaaataaat aaataaataa
     8641 aattatctcc ttgccaggac tgctggctca tgcctgtaat cccagcactc tgggaggcta
     8701 aggcaggagg attgctgacc caccacctgt tcttgagccc aggagttcga catcagcctt
     8761 ggacaacata gtgagactcc cgtgtctaca aaaaatttaa aaattagcca ggcatggtgg
     8821 caagtgtctg tagtctcagc tactcaggag gctaaggtgg aaggatcact tgaacccggg
     8881 aggtcgaggc tgcagtgagc tgtgatcttg ctattgcact tcagcctgaa tgacagagct
     8941 aagaccctga ctcaaaataa ataaataaca ttatctcttc aaaatgtatc tgaagccctg
     9001 atagttctac tttcaattct tagaaacata taaaaatata tgcatgatag ccatcatatc
     9061 aatggaagac tttctcacct ctgtggttgc agttagctta caaaaacgag caattttgct
     9121 tatactgtgt tgttcatctt ccttgttaat tctaaagctc tgatagactg agtttgacat
     9181 ttctttctgt aaactggaaa ttgttttcta tgaaaaaaaa actctatgat acacagttaa
     9241 agattggttg aggttgagat gaacttcaat actaagaaaa attgtggtgt tcctctgtgt
     9301 ggcctgcaat gaaaagaagg ctcatgcttg tgtattgagg tttgacatct ttccttcttt
     9361 gtttttagtc atgcaacgtc attcttagat ggcttttgaa tactatgcta atgactatct
     9421 aaatagataa atatgtgatt ggaaaacaaa gtcacctttt agttttctac ttggaaatat
     9481 taagagaatc cttgtagact ggaaacacac caaaaggctg ggtaaagcat gggaggttcc
     9541 agttaataga aagtaatttt aaaattggaa ataaaattaa atcaagacca gataatgcta
     9601 tggagactta cttattaaat aactttctga gcatttttat gtgcttagca ttacattttc
     9661 caagtaagag atacacaaca agagtgctat tttttcttct ttttatcttc ctacactcaa
     9721 agaccaagct agctttatca attctgaatt ttctctccta aaaatcagct caatctgtct
     9781 ttctgcctca tcagcactgc ctcaatctaa gggaggaaac cacccctcat attgtcttat
     9841 gcccaatttc tgcctccaaa gaaagaagaa gtaaaaacta aaaggcaaaa atgaaatcca
     9901 caggcagaca gcccggcgct acgccctggg cctggcagtt aaagatcgac ctctgaccta
     9961 accggttatg ttatctatag attccagaca ttgtatggaa gagcattgta aaaatccctg
    10021 tcctgtgctg tttcgttctg attactggtg catgcagtcc ccagtcacgt accccctgct
    10081 tgctcaatcg atcatgaccc tctcacgtgg acccccttag agttgtgagc ccttaaaagg
    10141 gacaggaatt gctcactcgg ggagctcggc tcttgagaca ggagtcttgc cgatgctcct
    10201 ggccgaataa actgctcctt ctttaa
//
