LOCUS       NM_001083               6959 bp    mRNA    linear   PRI 27-APR-2025
DEFINITION  Homo sapiens phosphodiesterase 5A (PDE5A), transcript variant 1,
            mRNA.
ACCESSION   NM_001083 NM_033431
VERSION     NM_001083.4
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 6959)
  AUTHORS   Lei,K., Liang,R., Liang,J., Lu,N., Huang,J., Xu,K., Tan,B.,
            Wang,K., Liang,Y., Wang,W., Lin,H. and Wang,M.
  TITLE     CircPDE5A-encoded novel regulator of the PI3K/AKT pathway inhibits
            esophageal squamous cell carcinoma progression by promoting
            USP14-mediated de-ubiquitination of PIK3IP1
  JOURNAL   J Exp Clin Cancer Res 43 (1), 124 (2024)
   PUBMED   38658954
  REMARK    GeneRIF: CircPDE5A-encoded novel regulator of the PI3K/AKT pathway
            inhibits esophageal squamous cell carcinoma progression by
            promoting USP14-mediated de-ubiquitination of PIK3IP1.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 6959)
  AUTHORS   Du,Q., Huang,L. and Guo,W.
  TITLE     LncRNA ARAP1-AS1 targets miR-516b-5p/PDE5A axis to facilitate the
            progression of thyroid cancer
  JOURNAL   Anticancer Drugs 34 (6), 735-746 (2023)
   PUBMED   36730555
  REMARK    GeneRIF: LncRNA ARAP1-AS1 targets miR-516b-5p/PDE5A axis to
            facilitate the progression of thyroid cancer.
REFERENCE   3  (bases 1 to 6959)
  AUTHORS   Cardarelli,S., Miele,A.E., Campolo,F., Massimi,M., Mancini,P.,
            Biagioni,S., Naro,F., Giorgi,M. and Saliola,M.
  TITLE     Cellular Redox Metabolism Is Modulated by the Distinct Localization
            of Cyclic Nucleotide Phosphodiesterase 5A Isoforms
  JOURNAL   Int J Mol Sci 23 (15), 8587 (2022)
   PUBMED   35955722
  REMARK    GeneRIF: Cellular Redox Metabolism Is Modulated by the Distinct
            Localization of Cyclic Nucleotide Phosphodiesterase 5A Isoforms.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 6959)
  AUTHORS   Lin,C.S., Lau,A., Tu,R. and Lue,T.F.
  TITLE     Expression of three isoforms of cGMP-binding cGMP-specific
            phosphodiesterase (PDE5) in human penile cavernosum
  JOURNAL   Biochem Biophys Res Commun 268 (2), 628-635 (2000)
   PUBMED   10679255
REFERENCE   5  (bases 1 to 6959)
  AUTHORS   Lin,C.S., Lau,A., Tu,R. and Lue,T.F.
  TITLE     Identification of three alternative first exons and an intronic
            promoter of human PDE5A gene
  JOURNAL   Biochem Biophys Res Commun 268 (2), 596-602 (2000)
   PUBMED   10679249
REFERENCE   6  (bases 1 to 6959)
  AUTHORS   Kotera,J., Fujishige,K., Imai,Y., Kawai,E., Michibata,H.,
            Akatsuka,H., Yanaka,N. and Omori,K.
  TITLE     Genomic origin and transcriptional regulation of two variants of
            cGMP-binding cGMP-specific phosphodiesterases
  JOURNAL   Eur J Biochem 262 (3), 866-873 (1999)
   PUBMED   10411650
REFERENCE   7  (bases 1 to 6959)
  AUTHORS   Loughney,K., Hill,T.R., Florio,V.A., Uher,L., Rosman,G.J.,
            Wolda,S.L., Jones,B.A., Howard,M.L., McAllister-Lucas,L.M.,
            Sonnenburg,W.K., Francis,S.H., Corbin,J.D., Beavo,J.A. and
            Ferguson,K.
  TITLE     Isolation and characterization of cDNAs encoding PDE5A, a human
            cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide
            phosphodiesterase
  JOURNAL   Gene 216 (1), 139-147 (1998)
   PUBMED   9714779
REFERENCE   8  (bases 1 to 6959)
  AUTHORS   Stacey,P., Rulten,S., Dapling,A. and Phillips,S.C.
  TITLE     Molecular cloning and expression of human cGMP-binding
            cGMP-specific phosphodiesterase (PDE5)
  JOURNAL   Biochem Biophys Res Commun 247 (2), 249-254 (1998)
   PUBMED   9642111
REFERENCE   9  (bases 1 to 6959)
  AUTHORS   Ito,M., Nishikawa,M., Fujioka,M., Miyahara,M., Isaka,N., Shiku,H.
            and Nakano,T.
  TITLE     Characterization of the isoenzymes of cyclic nucleotide
            phosphodiesterase in human platelets and the effects of E4021
  JOURNAL   Cell Signal 8 (8), 575-581 (1996)
   PUBMED   9115850
REFERENCE   10 (bases 1 to 6959)
  AUTHORS   Loughney,K., Martins,T.J., Harris,E.A., Sadhu,K., Hicks,J.B.,
            Sonnenburg,W.K., Beavo,J.A. and Ferguson,K.
  TITLE     Isolation and characterization of cDNAs corresponding to two human
            calcium, calmodulin-regulated, 3',5'-cyclic nucleotide
            phosphodiesterases
  JOURNAL   J Biol Chem 271 (2), 796-806 (1996)
   PUBMED   8557689
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF043731.1, AY264918.1,
            AC093752.2 and BM978332.1.
            
            On Nov 23, 2018 this sequence version replaced NM_001083.3.
            
            Summary: This gene encodes a cGMP-binding, cGMP-specific
            phosphodiesterase, a member of the cyclic nucleotide
            phosphodiesterase family. This phosphodiesterase specifically
            hydrolyzes cGMP to 5'-GMP. It is involved in the regulation of
            intracellular concentrations of cyclic nucleotides and is important
            for smooth muscle relaxation in the cardiovascular system.
            Alternative splicing of this gene results in three transcript
            variants encoding distinct isoforms. [provided by RefSeq, Jul
            2008].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1, also known as
            PDE5A1).
            
            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 :: BC126233.1, SRR1803611.275562.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2467148 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000354960.8/ ENSP00000347046.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-410               AF043731.1         23-432
            411-2821            AY264918.1         152-2562
            2822-6361           AC093752.2         96407-99946         c
            6362-6959           BM978332.1         25-622              c
FEATURES             Location/Qualifiers
     source          1..6959
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q26"
     gene            1..6959
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /note="phosphodiesterase 5A"
                     /db_xref="GeneID:8654"
                     /db_xref="HGNC:HGNC:8784"
                     /db_xref="MIM:603310"
     exon            1..285
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     CDS             134..2761
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /EC_number="3.1.4.35"
                     /note="isoform 1 is encoded by transcript variant 1;
                     cGMP-binding cGMP-specific 3',5'-cyclic nucleotide
                     phosphodiesterase; cGMP-specific phosphodiesterase type
                     5A; phosphodiesterase isozyme 5; cGMP-specific
                     phosphodiesterase PDE5A2; phosphodiesterase 5A,
                     cGMP-specific"
                     /codon_start=1
                     /product="cGMP-specific 3',5'-cyclic phosphodiesterase
                     isoform 1"
                     /protein_id="NP_001074.2"
                     /db_xref="CCDS:CCDS3713.1"
                     /db_xref="GeneID:8654"
                     /db_xref="HGNC:HGNC:8784"
                     /db_xref="MIM:603310"
                     /translation="MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSY
                     FVRKATREMVNAWFAERVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKIS
                     ASEFDRPLRPIVVKDSEGTVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDIS
                     SHLDVTALCHKIFLHIHGLISADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSN
                     NCIRLEWNKGIVGHVAALGEPLNIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHRE
                     EVVGVAQAINKKSGNGGTFTEKDEKDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLL
                     DLASLIFEEQQSLEVILKKIAATIISFMQVQKCTIFIVDEDCSDSFSSVFHMECEELE
                     KSSDTLTREHDANKINYMYAQYVKNTMEPLNIPDVSKDKRFPWTTENTGNVNQQCIRS
                     LLCTPIKNGKKNKVIGVCQLVNKMEENTGKVKPFNRNDEQFLEAFVIFCGLGIQNTQM
                     YEAVERAMAKQMVTLEVLSYHASAAEEETRELQSLAAAVVPSAQTLKITDFSFSDFEL
                     SDLETALCTIRMFTDLNLVQNFQMKHEVLCRWILSVKKNYRKNVAYHNWRHAFNTAQC
                     MFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGVNNSYIQRSEHPLAQLYCHSIME
                     HHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAILATDLALYIKRRGEFFELIR
                     KNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAELVATEFFDQGDRERKELN
                     IEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCFPLLDGCRKNRQKWQAL
                     AEQQEKMLINGESGQAKRN"
     exon            286..874
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            875..964
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            965..1036
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            1037..1126
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            1127..1264
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            1265..1332
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            1333..1441
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            1442..1529
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            1530..1705
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            1706..1765
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            1766..1912
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            1913..2038
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            2039..2133
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            2134..2221
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            2222..2322
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            2323..2400
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            2401..2464
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            2465..2539
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            2540..2623
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     exon            2624..6959
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5812..5817
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /note="hexamer: AATAAA"
     polyA_site      5834
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
     regulatory      6939..6944
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /note="hexamer: AATAAA"
     polyA_site      6959
                     /gene="PDE5A"
                     /gene_synonym="CGB-PDE; CN5A; PDE5"
                     /note="major polyA site"
ORIGIN      
        1 gtcgaaagcc ggcccgactg gagcaggacg aagggggagg gtctcgaggc cgagtcctgt
       61 tcttctgagg gacggacccc agctggggtg gaaaagcagt accagagagc ctccgaggcg
      121 cgcggtgcca accatggagc gggccggccc cagcttcggg cagcagcgac agcagcagca
      181 gccccagcag cagaagcagc agcagaggga tcaggactcg gtcgaagcat ggctggacga
      241 tcactgggac tttaccttct catactttgt tagaaaagcc accagagaaa tggtcaatgc
      301 atggtttgct gagagagttc acaccatccc tgtgtgcaag gaaggtatca gaggccacac
      361 cgaatcttgc tcttgtccct tgcagcagag tcctcgtgca gataacagtg cccctggaac
      421 accaaccagg aaaatctctg cctctgaatt tgaccggcct cttagaccca ttgttgtcaa
      481 ggattctgag ggaactgtga gcttcctctc tgactcagaa aagaaggaac agatgcctct
      541 aacccctcca aggtttgatc atgatgaagg ggaccagtgc tcaagactct tggaattagt
      601 gaaggatatt tctagtcatt tggatgtcac agccttatgt cacaaaattt tcttgcatat
      661 ccatggactg atatctgctg accgctattc cctgttcctt gtctgtgaag acagctccaa
      721 tgacaagttt cttatcagcc gcctctttga tgttgctgaa ggttcaacac tggaagaagt
      781 ttcaaataac tgtatccgct tagaatggaa caaaggcatt gtgggacatg tggcagcgct
      841 tggtgagccc ttgaacatca aagatgcata tgaggatcct cggttcaatg cagaagttga
      901 ccaaattaca ggctacaaga cacaaagcat tctttgtatg ccaattaaga atcataggga
      961 agaggttgtt ggtgtagccc aggccatcaa caagaaatca ggaaacggtg ggacatttac
     1021 tgaaaaagat gaaaaggact ttgctgctta tttggcattt tgtggtattg ttcttcataa
     1081 tgctcagctc tatgagactt cactgctgga gaacaagaga aatcaggtgc tgcttgacct
     1141 tgctagttta atttttgaag aacaacaatc attagaagta attttgaaga aaatagctgc
     1201 cactattatc tctttcatgc aagtgcagaa atgcaccatt ttcatagtgg atgaagattg
     1261 ctccgattct ttttctagtg tgtttcacat ggagtgtgag gaattagaaa aatcatctga
     1321 tacattaaca agggaacatg atgcaaacaa aatcaattac atgtatgctc agtatgtcaa
     1381 aaatactatg gaaccactta atatcccaga tgtcagtaag gataaaagat ttccctggac
     1441 aactgaaaat acaggaaatg taaaccagca gtgcattaga agtttgcttt gtacacctat
     1501 aaaaaatgga aagaagaata aagttatagg ggtttgccaa cttgttaata agatggagga
     1561 gaatactggc aaggttaagc ctttcaaccg aaatgacgaa cagtttctgg aagcttttgt
     1621 catcttttgt ggcttgggga tccagaacac gcagatgtat gaagcagtgg agagagccat
     1681 ggccaagcaa atggtcacat tggaggttct gtcgtatcat gcttcagcag cagaggaaga
     1741 aacaagagag ctacagtcgt tagcggctgc tgtggtgcca tctgcccaga cccttaaaat
     1801 tactgacttt agcttcagtg actttgagct gtctgatctg gaaacagcac tgtgtacaat
     1861 tcggatgttt actgacctca accttgtgca gaacttccag atgaaacatg aggttctttg
     1921 cagatggatt ttaagtgtta agaagaatta tcggaagaat gttgcctatc ataattggag
     1981 acatgccttt aatacagctc agtgcatgtt tgctgctcta aaagcaggca aaattcagaa
     2041 caagctgact gacctggaga tacttgcatt gctgattgct gcactaagcc acgatttgga
     2101 tcaccgtggt gtgaataact cttacataca gcgaagtgaa catccacttg cccagcttta
     2161 ctgccattca atcatggaac accatcattt tgaccagtgc ctgatgattc ttaatagtcc
     2221 aggcaatcag attctcagtg gcctctccat tgaagaatat aagaccacgt tgaaaataat
     2281 caagcaagct attttagcta cagacctagc actgtacatt aagaggcgag gagaattttt
     2341 tgaacttata agaaaaaatc aattcaattt ggaagatcct catcaaaagg agttgttttt
     2401 ggcaatgctg atgacagctt gtgatctttc tgcaattaca aaaccctggc ctattcaaca
     2461 acggatagca gaacttgtag caactgaatt ttttgatcaa ggagacagag agagaaaaga
     2521 actcaacata gaacccactg atctaatgaa cagggagaag aaaaacaaaa tcccaagtat
     2581 gcaagttggg ttcatagatg ccatctgctt gcaactgtat gaggccctga cccacgtgtc
     2641 agaggactgt ttccctttgc tagatggctg cagaaagaac aggcagaaat ggcaggccct
     2701 tgcagaacag caggagaaga tgctgattaa tggggaaagc ggccaggcca agcggaactg
     2761 agtggcctat ttcatgcaga gttgaagttt acagagatgg tgtgttctgc aatatgccta
     2821 gtttcttaca cactgtctgt atagtgtctg tatttggtat atactttgcc actgctgtat
     2881 ttttattttt gcacaacttt tgagagtata gcatgaatgt ttttagagga ctattacata
     2941 ttttttgtat atttgtttta tgctactgaa ctgaaaggat caacaacatc cactgttagc
     3001 acattgataa aagcattgtt tgtgatattt cgtgtactgc aaagtgtatg cagtattctt
     3061 gcactgaggt ttttttgctt ggggattatt ttaaataatt ggtttttgtg ttttctgaat
     3121 taccattttt tcaagaatgt ttggaatctt tcctttttca aaagtaggtt aggagcaaat
     3181 tatcatacat tctgtgacat ttaaagcctt tataggatag tgaaaaatgc tggctgagtg
     3241 gattttaaga gaaataattg tatttgttaa cagtgtcttt ttttaaaaag ttaaggcact
     3301 ctgaaacaaa tggaaagtcc tatgaaactg tattgtaaag aaaacattat ttaattgata
     3361 tgctgttttg tgagagaaca ggcaagacag aactttgtca cttcagtgca gtacattttt
     3421 ctgaaagcta cccataaaat cactttcatc tcacctacct gatgcaaagc aggtgaaacc
     3481 ttaggagatg atccagtcac tgacttgatt gagggataag tgtgatttag aaatggaatg
     3541 gccttggatg tctatcagtg aagaaaaatg ttctgttaga agatctctct aagagttttt
     3601 ttccttctga gcttcctttt caaaataaaa gtgacaattg tagcattgac ttgaagtgag
     3661 acatggttat agataagaga gtacaaaatg actctttttc ctgtcaattg aaatttaaag
     3721 aaaagtttta attatataaa tagcaaaggg ctattgccaa tactagggtc aaaaatgaat
     3781 ttgagggaac agtgggtaag aaactttatg cctgaataac atttagcagt attgtgattg
     3841 aaaaattgcc atattttgat gtataggaca agtcaactga gatccagaga atcctggatg
     3901 tgaatgctaa acactggccc ttaactcaca ttcaatgtat tttcttccca taacatttag
     3961 tatagttaat attttcttag aatttgagcc catttaagtg gattaatatt ctacatgtgt
     4021 gcccctaaag acacatttac tcaatattgg agaagtagat aatgaattaa gcaactggtc
     4081 taggaaagga aaatttgttt caaatatgca ggaatgtttg gatttgggga gagtagaagg
     4141 agagatttgc ttgatttgtt aacttctacc tccaacccac aaaaaagata tttgatctga
     4201 gtttctatca ctaatttgga tagaaaattt ctaagggaca tggtaatcca gcattctcaa
     4261 ggacctttcg ccaaaatgtg ttttccatct atgtcccgat tcccctaaat tttgcctaaa
     4321 attcagtatg ttccttaagt ttttaaaatt ctgagtgtgt acaaatatct tgacataatg
     4381 cagttttatt tttatcattc tggtaaaaaa acaaaaaata gaagcaaaac acattgtatt
     4441 gccattattt tgtatttggt aaaggttaat ctaggaagtt accaactgtt taatgctata
     4501 tgtattgtat acttgtattt tcaggatatt ttattttttt tgccatacag ataaaatttg
     4561 taaggttgcc cctttgtggc actggtgtgt aaaatacaca gactatcact aaaataatag
     4621 ttatatatac atacaggtgt atacttatgc atgcatacat aaatccttag tatagaaaaa
     4681 ttgcataaag aatagcaatc tttaataaac ctttttatta cattgtgatt tagcagttat
     4741 gctaaaatat gtacttatgc tttagtagtt tgtttggtcc cctctagtat gtgtcactga
     4801 gaaatttttt aaagacatgg tagatcgtgt ttagaggctt tgtatgtgtg tcattttaat
     4861 aagcaagaag atatatttag attagaaatg gtttggtctg cctttgaata ttgtttattt
     4921 tactttacta gttgagacat taaaggaagc tgggcaatgc ctattttatt tctttgttgg
     4981 atattttagt tcatacaaag cagagtactt ctttagggct ggttaattgg ttcaaataat
     5041 ttttaatttc ctttctagta tcttctcaag ttggaaaaat atacatacag tcctccttca
     5101 ccttactctg tatttatatt acccataact agcaagaagt tcttgttcta gattttttgt
     5161 ttgtttagtt ataacagagt aacataccat ttaattacaa tttttagcca gaaaagtccc
     5221 cactatttta ctaacttgtt aaaagatatc tatataattg cctggcctta tatttttcag
     5281 tagattagac cgtgccaatc acaatcctgg gtggatttgt gtaagtcact taacctctgt
     5341 gtgcctaaac aagttgtgct tttttaaaag gagttatgtt tgggcaaagc ctttgtcttc
     5401 aagcagaatg tcacagaagg cagctacttt ataagcccca atgggccatg gagaccactg
     5461 tcagaaatgg gatattagtc tagagagaag gtgatctatt cccacatgtc atttctaatg
     5521 ttgagtttcc atgactgaac aaagagaata tatttattca gcttcacttg cagatcacta
     5581 gtgaatgtga gatttagagc tcattgagta tattgcttca aggtacaaac ccaggatgat
     5641 gatgttgtca ccactgtctc ttaattttga ataatagttt cctttaatag gagtattaga
     5701 gataagaaag tatatgaaaa tatactggaa atattggatt cttggagaaa actgttcagt
     5761 cacagatata ttcttgccta gcagtgaagt gcctttattt tcagcatagc aaataaatat
     5821 tagacctgtt ccaatttgat ctacaatttt tttctgtgtt tttcaccaga ttgtactcct
     5881 aaaacttaac aggccatcac aagcaattgt cttttgttta caagattgat ttaatatgag
     5941 aggatacaaa atgtcatcgt tatcctctct tatgaacaac tgtagtcaaa ataaggtggc
     6001 acaatttaat tgttttgtat cagaaataca ctgacccacc ttttattgag tcctgccaca
     6061 tgttaggtac cgtgctctgc tgtggagaca gagcagtgac cccaaggagc tcacggtccc
     6121 tgaaggaggt gctagagaag agacttagct tctgatactg ccaatttaat gtgagaacat
     6181 ggggtatact gcatcatttc cattttcatc aataacatat gttttatgca ccttctttac
     6241 ctgaaactta ctaagaatct accagtaaac aaacatcctg tctttttgca agtatgaatc
     6301 acttaacctg ctgatagttg aagaacactt taggagtttt gtattcttgt atatagttta
     6361 ttttttccat gtgctagcca ggtaaagatt acacagttct tctggactgt taaattgtgc
     6421 atggttttgg accccttctg ctctactaca gagagtgaag aagaaagtat taaagctcac
     6481 tttaccattc catatactta ctaaaagcct gtgtaaacat gtcttaatga atgttgttga
     6541 aagcaatgta aatagttgaa aatataaatt tatattacag tttaagaaaa ccttatgagg
     6601 catcactagc cactgttaat atctatttgt attcttatac cttttcaata tatttgaaca
     6661 aatatagttt ctggcactat ttttatacta ggaaaaggag ttactatgta tattatgctt
     6721 agcttttaag gcattttaaa taaccatgaa tgttgatttc attactttcc tttcctccat
     6781 cacgagagtc atttcagatg actctttcat gacaaaatca ctttaaagga acacttacct
     6841 ccgattcctg tataaagtca tgagatggtc aaggtggttt tccattgtgc aaattcttca
     6901 cctgtcagtg gtttcctcat tttgccatgc tttgtaaaaa taaaaagaat gatcaagta
//
