LOCUS       NM_000921              12486 bp    mRNA    linear   PRI 01-JUL-2024
DEFINITION  Homo sapiens phosphodiesterase 3A (PDE3A), transcript variant 1,
            mRNA.
ACCESSION   NM_000921
VERSION     NM_000921.5
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 12486)
  AUTHORS   Yeh,C.Y., Cai,H.Y., Kuo,H.H., Lin,Y.Y., He,Z.J., Cheng,H.C.,
            Yang,C.J., Huang,C.F. and Chang,Y.C.
  TITLE     ALDOA coordinates PDE3A through the beta-catenin/ID3 axis to
            stimulate cancer metastasis and M2 polarization in lung cancer with
            EGFR mutations
  JOURNAL   Biochem Biophys Res Commun 696, 149489 (2024)
   PUBMED   38244313
  REMARK    GeneRIF: ALDOA coordinates PDE3A through the beta-catenin/ID3 axis
            to stimulate cancer metastasis and M2 polarization in lung cancer
            with EGFR mutations.
REFERENCE   2  (bases 1 to 12486)
  AUTHORS   Sholokh,A., Walter,S., Marko,L., McMurray,B.J., Sunaga-Franze,D.Y.,
            Xu,M., Zuhlke,K., Russwurm,M., Bartolomaeus,T.U.P., Langanki,R.,
            Qadri,F., Heuser,A., Patzak,A., Forslund,S.K., Bahring,S.,
            Borodina,T., Persson,P.B., Maass,P.G., Bader,M. and Klussmann,E.
  TITLE     Mutant phosphodiesterase 3A protects the kidney from
            hypertension-induced damage
  JOURNAL   Kidney Int 104 (2), 388-393 (2023)
   PUBMED   37244472
  REMARK    GeneRIF: Mutant phosphodiesterase 3A protects the kidney from
            hypertension-induced damage.
REFERENCE   3  (bases 1 to 12486)
  AUTHORS   Ercu,M., Walter,S. and Klussmann,E.
  TITLE     Mutations in Phosphodiesterase 3A (PDE3A) Cause Hypertension
            Without Cardiac Damage
  JOURNAL   Hypertension 80 (6), 1171-1179 (2023)
   PUBMED   37035914
  REMARK    GeneRIF: Mutations in Phosphodiesterase 3A (PDE3A) Cause
            Hypertension Without Cardiac Damage.
            Review article
REFERENCE   4  (bases 1 to 12486)
  AUTHORS   Skogestad,J., Albert,I., Hougen,K., Lothe,G.B., Lunde,M.,
            Eken,O.S., Veras,I., Huynh,N.T.T., Borstad,M., Marshall,S.,
            Shen,X., Louch,W.E., Robinson,E.L., Cleveland,J.C. Jr.,
            Ambardekar,A.V., Schwisow,J.A., Jonas,E., Calejo,A.I., Morth,J.P.,
            Tasken,K., Melleby,A.O., Lunde,P.K., Sjaastad,I., Carlson,C.R. and
            Aronsen,J.M.
  TITLE     Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases
            SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart
            Failure
  JOURNAL   Circulation 147 (16), 1221-1236 (2023)
   PUBMED   36876489
  REMARK    GeneRIF: Disruption of Phosphodiesterase 3A Binding to SERCA2
            Increases SERCA2 Activity and Reduces Mortality in Mice With
            Chronic Heart Failure.
REFERENCE   5  (bases 1 to 12486)
  AUTHORS   Ercu,M., Mucke,M.B., Pallien,T., Marko,L., Sholokh,A.,
            Schachterle,C., Aydin,A., Kidd,A., Walter,S., Esmati,Y.,
            McMurray,B.J., Lato,D.F., Yumi Sunaga-Franze,D., Dierks,P.H.,
            Flores,B.I.M., Walker-Gray,R., Gong,M., Merticariu,C., Zuhlke,K.,
            Russwurm,M., Liu,T., Batolomaeus,T.U.P., Pautz,S., Schelenz,S.,
            Taube,M., Napieczynska,H., Heuser,A., Eichhorst,J., Lehmann,M.,
            Miller,D.C., Diecke,S., Qadri,F., Popova,E., Langanki,R.,
            Movsesian,M.A., Herberg,F.W., Forslund,S.K., Muller,D.N.,
            Borodina,T., Maass,P.G., Bahring,S., Hubner,N., Bader,M. and
            Klussmann,E.
  TITLE     Mutant Phosphodiesterase 3A Protects From Hypertension-Induced
            Cardiac Damage
  JOURNAL   Circulation 146 (23), 1758-1778 (2022)
   PUBMED   36259389
  REMARK    GeneRIF: Mutant Phosphodiesterase 3A Protects From
            Hypertension-Induced Cardiac Damage.
REFERENCE   6  (bases 1 to 12486)
  AUTHORS   Lobbert,R.W., Winterpacht,A., Seipel,B. and Zabel,B.U.
  TITLE     Molecular cloning and chromosomal assignment of the human homologue
            of the rat cGMP-inhibited phosphodiesterase 1 (PDE3A)--a gene
            involved in fat metabolism located at 11p 15.1
  JOURNAL   Genomics 37 (2), 211-218 (1996)
   PUBMED   8921398
REFERENCE   7  (bases 1 to 12486)
  AUTHORS   Cheung,P.P., Xu,H., McLaughlin,M.M., Ghazaleh,F.A., Livi,G.P. and
            Colman,R.W.
  TITLE     Human platelet cGI-PDE: expression in yeast and localization of the
            catalytic domain by deletion mutagenesis
  JOURNAL   Blood 88 (4), 1321-1329 (1996)
   PUBMED   8695850
REFERENCE   8  (bases 1 to 12486)
  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
REFERENCE   9  (bases 1 to 12486)
  AUTHORS   Degerman,E., Moos,M. Jr., Rascon,A., Vasta,V., Meacci,E.,
            Smith,C.J., Lindgren,S., Andersson,K.E., Belfrage,P. and
            Manganiello,V.
  TITLE     Single-step affinity purification, partial structure and properties
            of human platelet cGMP inhibited cAMP phosphodiesterase
  JOURNAL   Biochim Biophys Acta 1205 (2), 189-198 (1994)
   PUBMED   8155697
REFERENCE   10 (bases 1 to 12486)
  AUTHORS   Meacci,E., Taira,M., Moos,M. Jr., Smith,C.J., Movsesian,M.A.,
            Degerman,E., Belfrage,P. and Manganiello,V.
  TITLE     Molecular cloning and expression of human myocardial cGMP-inhibited
            cAMP phosphodiesterase
  JOURNAL   Proc Natl Acad Sci U S A 89 (9), 3721-3725 (1992)
   PUBMED   1315035
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC129102.5 and AC112777.7.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Feb 11, 2020 this sequence version replaced NM_000921.4.
            
            Summary: This gene encodes a member of the cGMP-inhibited cyclic
            nucleotide phosphodiesterase (cGI-PDE) family. cGI-PDE enzymes
            hydrolyze both cAMP and cGMP, and play critical roles in many
            cellular processes by regulating the amplitude and duration of
            intracellular cyclic nucleotide signals. The encoded protein
            mediates platelet aggregation and also plays important roles in
            cardiovascular function by regulating vascular smooth muscle
            contraction and relaxation. Inhibitors of the encoded protein may
            be effective in treating congestive heart failure. Alternatively
            spliced transcript variants encoding multiple isoforms have been
            observed for this gene. [provided by RefSeq, Sep 2011].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: U36798.1, M91667.2 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000359062.4/ ENSP00000351957.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1708              AC129102.5         17338-19045
            1709-1759           AC112777.7         27060-27110
            1760-2017           AC112777.7         83843-84100
            2018-2172           AC112777.7         86630-86784
            2173-2288           AC112777.7         91696-91811
            2289-2508           AC112777.7         100308-100527
            2509-2594           AC112777.7         104093-104178
            2595-2749           AC112777.7         105302-105456
            2750-2887           AC112777.7         107500-107637
            2888-2999           AC112777.7         110246-110357
            3000-3113           AC112777.7         116890-117003
            3114-3313           AC112777.7         117151-117350
            3314-3517           AC112777.7         119088-119291
            3518-3673           AC112777.7         120845-121000
            3674-3932           AC112777.7         124347-124605
            3933-12486          AC112777.7         150430-158983
FEATURES             Location/Qualifiers
     source          1..12486
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12p12.2"
     gene            1..12486
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /note="phosphodiesterase 3A"
                     /db_xref="GeneID:5139"
                     /db_xref="HGNC:HGNC:8778"
                     /db_xref="MIM:123805"
     exon            1..1708
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     CDS             749..4174
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /EC_number="3.1.4.17"
                     /note="isoform 1 is encoded by transcript variant 1;
                     cGMP-inhibited 3',5'-cyclic phosphodiesterase A; cyclic
                     GMP-inhibited phosphodiesterase A; cAMP phosphodiesterase,
                     myocardial cGMP-inhibited; phosphodiesterase 3A,
                     cGMP-inhibited; cGMP-inhibited cAMP phosphodiesterase;
                     cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A"
                     /codon_start=1
                     /product="cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A
                     isoform 1"
                     /protein_id="NP_000912.3"
                     /db_xref="CCDS:CCDS31754.1"
                     /db_xref="GeneID:5139"
                     /db_xref="HGNC:HGNC:8778"
                     /db_xref="MIM:123805"
                     /translation="MAVPGDAARVRDKPVHSGVSQAPTAGRDCHHRADPASPRDSGCR
                     GCWGDLVLQPLRSSRKLSSALCAGSLSFLLALLVRLVRGEVGCDLEQCKEAAAAEEEE
                     AAPGAEGGVFPGPRGGAPGGGARLSPWLQPSALLFSLLCAFFWMGLYLLRAGVRLPLA
                     VALLAACCGGEALVQIGLGVGEDHLLSLPAAGVVLSCLAAATWLVLRLRLGVLMIALT
                     SAVRTVSLISLERFKVAWRPYLAYLAGVLGILLARYVEQILPQSAEAAPREHLGSQLI
                     AGTKEDIPVFKRRRRSSSVVSAEMSGCSSKSHRRTSLPCIPREQLMGHSEWDHKRGPR
                     GSQSSGTSITVDIAVMGEAHGLITDLLADPSLPPNVCTSLRAVSNLLSTQLTFQAIHK
                     PRVNPVTSLSENYTCSDSEESSEKDKLAIPKRLRRSLPPGLLRRVSSTWTTTTSATGL
                     PTLEPAPVRRDRSTSIKLQEAPSSSPDSWNNPVMMTLTKSRSFTSSYAISAANHVKAK
                     KQSRPGALAKISPLSSPCSSPLQGTPASSLVSKISAVQFPESADTTAKQSLGSHRALT
                     YTQSAPDLSPQILTPPVICSSCGRPYSQGNPADEPLERSGVATRTPSRTDDTAQVTSD
                     YETNNNSDSSDIVQNEDETECLREPLRKASACSTYAPETMMFLDKPILAPEPLVMDNL
                     DSIMEQLNTWNFPIFDLVENIGRKCGRILSQVSYRLFEDMGLFEAFKIPIREFMNYFH
                     ALEIGYRDIPYHNRIHATDVLHAVWYLTTQPIPGLSTVINDHGSTSDSDSDSGFTHGH
                     MGYVFSKTYNVTDDKYGCLSGNIPALELMALYVAAAMHDYDHPGRTNAFLVATSAPQA
                     VLYNDRSVLENHHAAAAWNLFMSRPEYNFLINLDHVEFKHFRFLVIEAILATDLKKHF
                     DFVAKFNGKVNDDVGIDWTNENDRLLVCQMCIKLADINGPAKCKELHLQWTDGIVNEF
                     YEQGDEEASLGLPISPFMDRSAPQLANLQESFISHIVGPLCNSYDSAGLMPGKWVEDS
                     DESGDTDDPEEEEEEAPAPNEEETCENNESPKKKTFKRRKIYCQITQHLLQNHKMWKK
                     VIEEEQRLAGIENQSLDQTPQSHSSEQIQAIKEEEEEKGKPRGEEIPTQKPDQ"
     exon            1709..1759
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            1760..2017
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            2018..2172
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            2173..2288
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            2289..2508
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            2509..2594
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            2595..2749
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            2750..2887
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            2888..2999
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            3000..3113
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            3114..3313
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            3314..3517
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            3518..3673
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            3674..3932
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     exon            3933..12486
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /inference="alignment:Splign:2.1.0"
     regulatory      7960..7965
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /note="hexamer: TATAAA"
     regulatory      7979..7984
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /note="hexamer: AATAAA"
     polyA_site      7980
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /note="major polyA site"
     polyA_site      8002
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
     regulatory      11513..11518
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /note="hexamer: AATAAA"
     polyA_site      11536
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
     regulatory      12466..12471
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
                     /note="hexamer: TATAAA"
     polyA_site      12486
                     /gene="PDE3A"
                     /gene_synonym="CGI-PDE; CGI-PDE A; CGI-PDE-A; HTNB"
ORIGIN      
        1 gctagtctct cggtctggct ctctctccga cgggacttag caacttctta tttctcagcc
       61 ccttgtccat tttttttttt ccatcctttg ccatgaattg gattgacaga ggcgggggag
      121 gctttgcttt ctgccccagg gaatggcgat tcgcgtcctg gggccgtgcc ggggagaatc
      181 ggccgaggag aaagaaagag tgatagaaaa agagctgcag gaaggaggag aagggagacc
      241 tccatctgcc gcgggcccgg cgcgctgcag cgcagcgcag cgccgagctg cgcctcggaa
      301 tggcccggag cccgccctgc gcccccggct cctccagcgt cagcggctcc tgcgcgcggg
      361 atgcattggg caatttttga aatcctgaag taggaagaga ccccggagga tataagtcgg
      421 gggtgggggt ggagcagaga atctgtgaaa gatattcaaa gagagaaaag gggaatcctg
      481 atcgtttctg cccgtgcttg ttttcaactt gagcgtgcta gcctttaact tgaagaagtc
      541 tcattggagc atctagcatt ctccaggagt tattcgaaag ctgaaacttt cagtggattg
      601 tgggcctggg gagaagaagg attccgaggg tggaattggg aagagcgtgc gtgcgtgtgt
      661 gtgtgtgtgt gtgtgcgcgc gcgcgcgtgg gtcggggcgg gggcgtcggg gggccactgg
      721 gaattcagtg aagagggcac cctataccat ggcagtgccc ggcgacgctg cacgagtcag
      781 ggacaagccc gtccacagtg gggtgagtca agcccccacg gcgggccggg actgccacca
      841 tcgtgcggac cccgcatcgc cgcgggactc gggctgccgt ggctgctggg gagacctggt
      901 gctgcagccg ctccggagct ctcggaaact ttcctccgcg ctgtgcgcgg gctccctgtc
      961 ctttctgctg gcgctgctgg tgaggctggt ccgcggggag gtcggctgtg acctggagca
     1021 gtgtaaggag gcggcggcgg cggaggagga ggaagcagcc ccgggagcag aagggggcgt
     1081 cttcccgggg cctcggggag gtgctcccgg gggcggtgcg cggctcagcc cctggctgca
     1141 gccctcggcg ctgctcttca gtctcctgtg tgccttcttc tggatgggct tgtacctcct
     1201 gcgcgccggg gtgcgcctgc ctctggctgt cgcgctgctg gccgcctgct gcggggggga
     1261 agcgctcgtc cagattgggc tgggcgtcgg ggaggatcac ttactctcac tccccgccgc
     1321 gggggtggtg ctcagctgct tggccgccgc gacatggctg gtgctgaggc tgaggctggg
     1381 cgtcctcatg atcgccttga ctagcgcggt caggaccgtg tccctcattt ccttagagag
     1441 gttcaaggtc gcctggagac cttacctggc gtacctggcc ggcgtgctgg ggatcctctt
     1501 ggccaggtac gtggaacaaa tcttgccgca gtccgcggag gcggctccaa gggagcattt
     1561 ggggtcccag ctgattgctg ggaccaagga agatatcccg gtgtttaaga ggaggaggcg
     1621 gtccagctcc gtcgtgtccg ccgagatgtc cggctgcagc agcaagtccc atcggaggac
     1681 ctccctgccc tgtataccga gggaacagct catggggcat tcagaatggg accacaaacg
     1741 agggccaaga ggatcacagt cttcaggaac cagtattact gtggacatcg ccgtcatggg
     1801 cgaggcccac ggcctcatta ccgacctcct ggcagaccct tctcttccac caaacgtgtg
     1861 cacatccttg agagccgtga gcaacttgct cagcacacag ctcaccttcc aggccattca
     1921 caagcccaga gtgaatcccg tcacttcgct cagtgaaaac tatacctgtt ctgactctga
     1981 agagagctct gaaaaagaca agcttgctat tccaaagcgc ctgagaagga gtttgcctcc
     2041 tggcttgttg agacgagttt cttccacttg gaccaccacc acctcggcca caggtctacc
     2101 caccttggag cctgcaccag tacggagaga ccgcagcacc agcatcaaac tgcaggaagc
     2161 accttcatcc agtcctgatt cttggaataa tccagtgatg atgaccctca ccaaaagcag
     2221 atcctttact tcatcctatg ctatttctgc agctaaccat gtaaaggcta aaaagcaaag
     2281 tcgaccaggt gccctcgcta aaatttcacc tctttcatcg ccctgctcct cacctctcca
     2341 agggactcct gccagcagcc tggtcagcaa aatttctgca gtgcagtttc cagaatctgc
     2401 tgacacaact gccaaacaaa gcctaggttc tcacagggcc ttaacttaca ctcagagtgc
     2461 cccagaccta tcccctcaaa tcctgactcc acctgttata tgtagcagct gtggcagacc
     2521 atattcccaa gggaatcctg ctgatgagcc cctggagaga agtggggtag ccactcggac
     2581 accaagtaga acagatgaca ctgctcaagt tacctctgat tatgaaacca ataacaacag
     2641 tgacagcagt gacattgtac agaatgaaga tgaaacagag tgcctgagag agcctctgag
     2701 gaaagcatcg gcttgcagca cctatgctcc tgagaccatg atgtttctgg acaaaccaat
     2761 tcttgctccc gaacctcttg tcatggataa cctggactca attatggagc agctaaatac
     2821 ttggaatttt ccaatttttg atttagtgga aaatatagga agaaaatgtg gccgtattct
     2881 tagtcaggta tcttacagac tttttgaaga catgggcctc tttgaagctt ttaaaattcc
     2941 aattagggaa tttatgaatt attttcatgc tttggagatt ggatataggg atattcctta
     3001 tcataacaga atccatgcca ctgatgtttt acatgctgtt tggtatctta ctacacagcc
     3061 tattccaggc ctctcaactg tgattaatga tcatggttca accagtgatt cagattctga
     3121 cagtggattt acacatggac atatgggata tgtattctca aaaacgtata atgtgacaga
     3181 tgataaatac ggatgtctgt ctgggaatat ccctgccttg gagttgatgg cgctgtatgt
     3241 ggctgcagcc atgcacgatt atgatcatcc aggaaggact aatgctttcc tggttgcaac
     3301 tagtgctcct caggcggtgc tatataacga tcgttcagtt ttggagaatc atcacgcagc
     3361 tgctgcatgg aatcttttca tgtcccggcc agagtataac ttcttaatta accttgacca
     3421 tgtggaattt aagcatttcc gtttccttgt cattgaagca attttggcca ctgacctgaa
     3481 gaaacacttt gacttcgtag ccaaatttaa tggcaaggta aatgatgatg ttggaataga
     3541 ttggaccaat gaaaatgatc gtctactggt ttgtcaaatg tgtataaagt tggctgatat
     3601 caatggtcca gctaaatgta aagaactcca tcttcagtgg acagatggta ttgtcaatga
     3661 attttatgaa cagggtgatg aagaggccag ccttggatta cccataagcc ccttcatgga
     3721 tcgttctgct cctcagctgg ccaaccttca ggaatccttc atctctcaca ttgtggggcc
     3781 tctgtgcaac tcctatgatt cagcaggact aatgcctgga aaatgggtgg aagacagcga
     3841 tgagtcagga gatactgatg acccagaaga agaggaggaa gaagcaccag caccaaatga
     3901 agaggaaacc tgtgaaaata atgaatctcc aaaaaagaag actttcaaaa ggagaaaaat
     3961 ctactgccaa ataactcagc acctcttaca gaaccacaag atgtggaaga aagtcattga
     4021 agaggagcaa cggttggcag gcatagaaaa tcaatccctg gaccagaccc ctcagtcgca
     4081 ctcttcagaa cagatccagg ctatcaagga agaagaagaa gagaaaggga aaccaagagg
     4141 cgaggagata ccaacccaaa agccagacca gtgacaatgg atagaatggg ctgtgtttcc
     4201 aaacagattg acttgtcaaa gactctcttc aagccagcac aacatttaga cacaacactg
     4261 tagaaatttg agatgggcaa atggctattg cattttggga ttcttcgcat tttgtgtgta
     4321 tatttttaca gtgaggtaca ttgttaaaaa ctttttgctc aaagaagctt tcacattgca
     4381 acaccagctt ctaaggattt tttaaggagg gaatatatat gtgtgtgtgt atataagctc
     4441 ccacatagat acatgtaaaa catattcaca cccatgcacg cacacacata cacactgaag
     4501 gccacgattg ctggctccac aatttagtaa catttatatt aagatatata tatagtggtc
     4561 actgtgatat aataaatcat aaaggaaacc aaatcacaaa ggagatggtg tggcttagca
     4621 aggaaacagt gcaggaaatg taggttacca actaagcagc ttttgctctt agtactgagg
     4681 gatgaaagtt ccagagcatt atttgaattc tgatacatcc tgccaacact gtgtgtgtgt
     4741 gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgaaagaga gacagaaggg aatggtttga
     4801 gagggtgctt gtgtgcatgt gtgtgcatat gtaaagagat ttttgtggtt taagtaactc
     4861 agaatagctg tagcaaatga ctgaatacat gtgaacaaac agaaggaagt tcactctgga
     4921 gtgtctttgg gaggcagcca ttccaaatgc cctcctccat ttagcttcaa taaagggcct
     4981 tttgctgatg gagggcactc aagggctggg tgagagggcc acgtgtttgg tattacatta
     5041 ctgctatgca ccacttgaag gagctctatc accagcctca aacccgaaag actgaggcat
     5101 tttccagtct acttgcctaa tgaatgtata ggaactgtct atgagtatgg atgtcactca
     5161 actaagatca aatcaccatt taaggggatg gcattcttta tacctaaaca cctaagagct
     5221 gaagtcaggt cttttaatca ggttagaatt ctaaatgatg ccagagaagg cttgggaaat
     5281 tgtacttcag cgtgatagcc tgtgtcttct taatttgctg caaaatatgt ggtagagaaa
     5341 gaaaaggaaa cagaaaaatc actctgggtt atatagcaag agatgaagga gaatatttca
     5401 acacagggtt tttgtgttga cataggaaaa gcctgattct tggcaactgt tgtagtttgt
     5461 ctttcagggg tgaaggtccc actgacaacc cctgttgtgg tgttccacac gctgtttgtt
     5521 ggggtagctt ccatcggcag tctggcccat tgtcagtcat gcttcttctg gccggggaga
     5581 ttatagagag attgtttgaa gattgggtta ttattgaaag tctttttttt tgtttgtttt
     5641 gttttggttt gtttgtttat ctacacttgt ttatgctgtg agccaaacct ctatttaaaa
     5701 agttgatact cactttcaat attttatttc atattattat atatgtcatg atagttatct
     5761 tgatgtaaat atgaagattt ttttgtttct gtagatagta aactcttttt ttaaaaaagg
     5821 aaaagggaaa catttttata aagttatatt ttaatcacca tttttataca ttgtagttct
     5881 ctccaagccc agtaagagaa tgatgattca tttgcatgga ggtcgatgga caaccaatca
     5941 tctacctttt ctaatttaaa tgataatctg atatagtttt attgccagtt aaatgaggat
     6001 gctgcaaagc atgttttttc actagtaact tttgctaact gaatgaattc tgggtccata
     6061 tctcccagat gaaaaactgt taaccaatac catattttat agttggtgtc catttctttc
     6121 caacactgtt tgttatgatt cttccttgag tacttatata cagacctgct cattatctaa
     6181 acaatcttac cttctaagta aaccttgatt gtgatttcca gtttttattt tctctgacgt
     6241 agtagaaagg aatgtttaca ttaaaaatac ttttgtttct cataaatgga tattgtactc
     6301 ccccctttca aagcattatt ttacaataat tcatggcatt ttaaaaaata aggcaaagat
     6361 aatacgacaa aaaatataca tggtttcaag gcaaattctc caataagttg gaaaatgtaa
     6421 aaaggatcaa gtggatgcag cctctaccta aataattaaa atatatttca gtatatttct
     6481 gaattaacac caggtcttca ttatttagaa cttactaaat tgttttcatt ttcttagttt
     6541 tacctgtgta tctccatgtt tgcaaaaatt actataagtc aaattttgcc agtgaattta
     6601 actatttttc tttccttgca attaagggga aaaaagcatt tatcttatct tctcataccc
     6661 cttgcatcta agtacttagc aaagtcaata ttttcccatt ttccaaatgc gtccatctct
     6721 aacataaata ttaattgaac atagagctat gtttggagtg agtggactgg caggacagtt
     6781 ggaagtccat cacagtctat tgacagtttc atcaaagctg tatagtccaa ctagtggggc
     6841 agcttggcta ctatggtgga agtctcagca aactgcctgg ttttgtttgt ttgttttgtt
     6901 ttaaggtaca ggaaataaga ggaataatag tggccaaagc aattagaaca tcttcattcc
     6961 agaactgtgt tcagcaatcc aggcagattg atacattttt ctttaaaaat aaattgctat
     7021 tacagctaga cgtcaattgg gataaataaa gggatgaaga tccactaagt ttgtgacttt
     7081 catacacacc cagtacatct caaaggatgc taagggacat tttctgccag tagagttctc
     7141 cccctttttg gtgacagcaa tattattatg ttcacatcta actccagagc ttacttcctg
     7201 tggtgccaat gtatttgttg caatttacta catttttata tgagcctatt tataggtgcc
     7261 attaaactca ggtctttcaa atgaaagagt ttctagccca cttagggaaa aagataattg
     7321 tttagaaaac cataaaatca atggtaggaa aagttggaac tggttacctg gatgccatgg
     7381 ttctctgtta aataaagtaa gagaccaggt gtattctgag tgtcatcagt gttattttca
     7441 gcatgctaat aaatgtcttt ccggttatat atctatctaa attaaccttt aaaatattgg
     7501 tttccttgat aaaagcacca cttttgcttt tgttagctgt aatatttttt gtcatttaga
     7561 taagacctgg tttggctctc aataaaagat gaagacagta gctctgtaca gggatatatc
     7621 tatattagtc ttcatctgat gaatgaagaa attttctcat attatgttca agaaagtatt
     7681 tacttcctaa aaatagaatt cccgattctg tctattttgg ttgaatacca gaacaaatct
     7741 ttccgttgca atcccagtaa aacgaaagaa aaggaatatc ttacagactg ttcatattag
     7801 atgtatgtag actgttaatt tgcaatttcc ccatatttcc tgcctatctt acccagataa
     7861 ctttctttga aggtaaaagc tgtgcaaaag gcatgagact caggcctact ctttgtttaa
     7921 atgatggaaa aatataaatt attttctaag taataaaagt ataaaaatta tcattataaa
     7981 taaagtctaa agtttgaaat tattaattta taaaagtgaa ctaattgtgt gattatcaaa
     8041 tcctgattaa tgagaagtga ataatctaaa aatcatttat attctactgt gggaggtatt
     8101 cttggtgctt ccatgtcagt atcgggctct ccattgtcct catcatttat agtacttcta
     8161 aaataataat ggaaacctca ataagggtct tgtcctcttc tgtcatccta accctgattc
     8221 tagtttaatg cctttcctga cttatatgcc atttgtaaat aaacttcctt tcaaactgtt
     8281 agaacgctcc aataaaacaa agttctatga actttcatag tctagaaaaa ccaacaagat
     8341 cccccttatt tagagattat tagctaatgt gtgaaagaaa tatcaataga agttcaaatg
     8401 ctaatagctc aattccagat aattgaaagc taaaatatct atgtactttg aagccaaact
     8461 gagtttattt cattgatcga acaagcagca acacatttta tgaccattgt cctaggtcgt
     8521 ttgtgtcttt atgaatttgc tgatattgtc agtccatttt ttaaatcttc aacaaaattc
     8581 aattttaaga ttaagaaatc agcaatttta ggtaaagaat attccaagat taaattgttc
     8641 tttttaagaa atatatcagt tttaggtcct atgttcacac atcaatttgt tcatctggaa
     8701 gatattcaaa ttcttattgg gaatgaatta cactacaaac aatgagttga gctaaaaact
     8761 atacataact taaattgaga tttgcatacg tatttgtgtg tttcacacca aagacccatg
     8821 ctcagagaat ggtaacatat tttccagtct atgttatgca ccatggatgt taggcaatgt
     8881 gtgctattgc caacacatgg tatttgttga aatacatgtt gctttgacct tacctaatgg
     8941 tgcttttacc taacttgaag tgctttttgt gttcccacca gcaaatcatt ctaacagcag
     9001 gctaacaatg gtgaagtaaa atgaacattt ttgggccggg cgcagtggct cacgcctgta
     9061 atcccagcac tttgggaggc caaggctggt ggatcacctg aggtcgggag ttcgacacca
     9121 gcctgaccaa cacggagaaa ccccgtcttt actaaaaata caaaatgatt caggtgtggt
     9181 ggcgcatgtc tgtaatccca gctacccagg aggctgaggc agaatcgctt gaacctggga
     9241 ggcagaggtt atggtgagct gagattgcac cattgcactc cagcctgggc aacaggagtt
     9301 aaattttgcc tcaaaaaaaa aaaaaaaaaa aaaaagaaca ttttttggca aaatatgaag
     9361 acacgaaact gaagataaag gcttcatttc catagtggaa atcagtgttt acctgctgat
     9421 tcaaaaatac tgacctagta tcagtgtagg taagaccata aaatacagtg tatagaatta
     9481 tatataaatg gaaaacaaaa ttagcttttg acatatgttt aagtctctaa aaggaatcca
     9541 cattttcttt ccagatacag ctagtttttc tccacatgtt tttaaggttg atttccttga
     9601 cacacattgg tatccttggg tttctgcttc cttgaaaagt tgtggagcac agaagaaaag
     9661 ccttctcttt acagataaaa aatgttgaac atgttcatgt tctgacaatg aagcaatgat
     9721 ttcctcattg ctttgcatta agaagtggtt ctttagttat gcaaataatt caataaccaa
     9781 aaatgcttca aagagtaata ataaatcacc ataggtaagt attctcaaga atgtttaaat
     9841 ttggtttatt ttcttgaagc aaagttattt aattttttaa tttttaactt aaaatgaaac
     9901 ccacaaaatg acattccgtg gtactgagta ttttcacata atcagaactg taaactactg
     9961 attattttca tatactcaga ggctgaatat tttgatataa taagaactag tatcatataa
    10021 cagaaaacta gaaagaaggt ttaattcttt ttctaatatt ctacaagcct catggggaaa
    10081 atgttttatg aaggattcaa atacattaga taaaaattag tgtcaataat ttaactttgt
    10141 acaaattata gtctgagatc ttctgagttt tcctaagaca aaggagtgta ttatccagca
    10201 atttattgtt ttgtgttgtt ataaaataaa tgttctatta atgtatattt tattttacta
    10261 agttctaaca caaaaggcca aatacttatc tttcctacta agaaaaatta aaccttacta
    10321 atcttgactt tcacagatga aacactgacc agtcaataaa caacagccac tgcattaatc
    10381 tgcccagcat gatcagatag taggttagaa tttgaaattc attaataaaa aattaataac
    10441 aaaactttgt aagccttaat ggtttaatat ttccgtgtca ttgaaagttc ctatttcaaa
    10501 ttaaacaaac tacagcagga tatttttcct ttcctgtttc aaaacaaaaa ccagatgaag
    10561 aaaaaacaaa gacaaactca taggaggaaa gcatggcttc tcttcaatta tacttctctt
    10621 actcaatatt agtaaccaaa aaataagcag aaattctcct ctgccataat taaaagaaag
    10681 aatggccttc gacttaagtt ctagttcctc aagcctgctt tccttgtaaa gtccatggta
    10741 ctaagaagca aaaaatgcag agctgtggat tgggagtgaa cactacataa aatttgcagg
    10801 gtatcccagg acacccctca gtctttaata caaaccaatt tagttactct ggagtgaaat
    10861 gacttgtgga tacactgttc aaccatgact tcctttatga caaggagcac ttatacatgt
    10921 ttccaaatgt gaattagccc ttgaattagt ttgaaaactg ctacttgaat aacttttgaa
    10981 gagaaagatt ttctttccgg taattttact ccctaaaaaa ggcaaaatac tcagatgttc
    11041 aatgtgaaat tacaaatagt tgtttgaagt atatatactt caataaatag ttctttgtgt
    11101 atataaagtg ttggttcata gcagtttcct tgtccctttt ctttttaaaa ttcccaactg
    11161 attatgggtc aaaaactcca tcttatatca gcgatgattt cattttaact atttataagg
    11221 ataatttagt attatagtat tgctaacttt aataattcta ccatatctat atattacctg
    11281 ttagtgaggt tttaatggct ttacttaata catatttgtt catcagctta aaaaatcact
    11341 aaatttttta tactctgtaa aatatttgca tgggaatttt agcttattat gtttgcttaa
    11401 ctggtgtttt tttcacttat gactgtcagt ttatgtctta atgtattctc acagaagaat
    11461 gcataccatt tttgttccaa caagaacaat ctgttagttg ataagcactg gtaataaata
    11521 tcactgaacc cacccacccc ctgatatttc ttcctcaagt tttctatcat gcaaatcaca
    11581 aaatgaaaat tggtgctttt acaaatattt gaaagctctc aatgcaaaat aataaaaatg
    11641 agattctccc tggctttcta taatatatta ggatatgtga ctgaaggaaa tttaatctga
    11701 atttagagtg ttttaggttt tggttggttt gaataatttg atttgcattt tggtattaaa
    11761 atgtgctctg atttctgcgg gcatttgttc tgaccagtca ttacctcttc ccaacagaaa
    11821 aaaaaaaaaa aaaaaaaaaa ctggcattgg caagttttaa ttaatatggc ccaaaaattt
    11881 gaccttgaag gatatttgta aaccagagag tatttaatta actaaattta ctgtttctga
    11941 aaagcaatat tttcaaataa ctgccaacca aagtgacact atagggatgt catttgtaca
    12001 tgacaatttt taacaatgta attcttacca ctctcgacag acctgaatat gtttactaat
    12061 aactttgcca aatttttcaa cttctagaaa aacaagagtg agtcttttga acttcatcat
    12121 tttgcaattg aaataaatct tgtcctttca cctatatctt ccatttaata tatgtagcaa
    12181 tacttagtat catcccatca caagtattgt taggcgactt agtggcggag aaatgtttgt
    12241 aaaaagtaga atctgtacag aaaaaaaact agatcaattg tatttatttt tattattttt
    12301 tagcttagat actatgttga tgctcccttt ttgccagaat tactggaagt gcctcttggt
    12361 tttatatata taatatataa atattacagt aaatatatac tcaaaattat taaaattatg
    12421 tcctagatta tctatgtcga tgttatgagt gaagataatg tataatataa aaataattct
    12481 gcagta
//
