LOCUS       NM_004969               5894 bp    mRNA    linear   PRI 08-JUN-2024
DEFINITION  Homo sapiens insulin degrading enzyme (IDE), transcript variant 1,
            mRNA.
ACCESSION   NM_004969
VERSION     NM_004969.4
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 5894)
  AUTHORS   Kullenberg,H., Nystrom,T., Kumlin,M. and Svedberg,M.M.
  TITLE     Correlation between insulin-degrading enzyme versus total tau and
            selected cytokines in patients with Alzheimer s disease compared to
            non-demented controls
  JOURNAL   Neuro Endocrinol Lett 44 (4), 199-205 (2023)
   PUBMED   37466059
  REMARK    GeneRIF: Correlation between insulin-degrading enzyme versus total
            tau and selected cytokines in patients with Alzheimer s disease
            compared to non-demented controls.
REFERENCE   2  (bases 1 to 5894)
  AUTHORS   Yilmaz,A., Guerrera,C., Waeckel-Enee,E., Lipecka,J., Bertocci,B.
            and van Endert,P.
  TITLE     Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and
            Respiratory Chain Proteins
  JOURNAL   Biomolecules 13 (6), 890 (2023)
   PUBMED   37371470
  REMARK    GeneRIF: Insulin-Degrading Enzyme Interacts with Mitochondrial
            Ribosomes and Respiratory Chain Proteins.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 5894)
  AUTHORS   Abramov-Harpaz,K. and Miller,Y.
  TITLE     Insights into Non-Proteolytic Inhibitory Mechanisms of Polymorphic
            Early-Stage Amyloid beta Oligomers by Insulin Degrading Enzyme
  JOURNAL   Biomolecules 12 (12), 1886 (2022)
   PUBMED   36551314
  REMARK    GeneRIF: Insights into Non-Proteolytic Inhibitory Mechanisms of
            Polymorphic Early-Stage Amyloid beta Oligomers by Insulin Degrading
            Enzyme.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 5894)
  AUTHORS   Abdul Aziz,M., Md Ashraf,G. and Safiqul Islam,M.
  TITLE     Link of BIN1, CLU, and IDE Gene Polymorphisms with the
            Susceptibility of Alzheimer's Disease: Evidence from a
            Meta-analysis
  JOURNAL   Curr Alzheimer Res 19 (4), 302-316 (2022)
   PUBMED   35546756
  REMARK    GeneRIF: Link of BIN1, CLU, and IDE Gene Polymorphisms with the
            Susceptibility of Alzheimer's Disease: Evidence from a
            Meta-analysis.
REFERENCE   5  (bases 1 to 5894)
  AUTHORS   Sery,O., Zeman,T., Halova,A., Janout,V., Janoutova,J., Lochman,J.
            and Balcar,V.J.
  TITLE     Polymorphism Rs2421943 of the Insulin-Degrading Enzyme Gene and the
            Risk of Late-Onset Alzheimer's Disease
  JOURNAL   Curr Alzheimer Res 19 (3), 236-245 (2022)
   PUBMED   35236268
  REMARK    GeneRIF: Polymorphism Rs2421943 of the Insulin-Degrading Enzyme
            Gene and the Risk of Late-Onset Alzheimer's Disease.
REFERENCE   6  (bases 1 to 5894)
  AUTHORS   Farris,W., Leissring,M.A., Hemming,M.L., Chang,A.Y. and Selkoe,D.J.
  TITLE     Alternative splicing of human insulin-degrading enzyme yields a
            novel isoform with a decreased ability to degrade insulin and
            amyloid beta-protein
  JOURNAL   Biochemistry 44 (17), 6513-6525 (2005)
   PUBMED   15850385
  REMARK    GeneRIF: This study systematically characterizes IDE mRNAs,
            identifies a novel, catalytically inefficient splice form and
            compares its subcellular distribution, kinetic properties and
            ability to degrade amyloid beta protein to the known isoform.
REFERENCE   7  (bases 1 to 5894)
  AUTHORS   Wroblewski,V.J., Masnyk,M., Khambatta,S.S. and Becker,G.W.
  TITLE     Mechanisms involved in degradation of human insulin by cytosolic
            fractions of human, monkey, and rat liver
  JOURNAL   Diabetes 41 (4), 539-547 (1992)
   PUBMED   1607078
REFERENCE   8  (bases 1 to 5894)
  AUTHORS   Ding,L., Becker,A.B., Suzuki,A. and Roth,R.A.
  TITLE     Comparison of the enzymatic and biochemical properties of human
            insulin-degrading enzyme and Escherichia coli protease III
  JOURNAL   J Biol Chem 267 (4), 2414-2420 (1992)
   PUBMED   1733942
REFERENCE   9  (bases 1 to 5894)
  AUTHORS   Espinosa,R. 3rd, Lemons,R.S., Perlman,R.K., Kuo,W.L., Rosner,M.R.
            and Le Beau,M.M.
  TITLE     Localization of the gene encoding insulin-degrading enzyme to human
            chromosome 10, bands q23----q25
  JOURNAL   Cytogenet Cell Genet 57 (4), 184-186 (1991)
   PUBMED   1743072
REFERENCE   10 (bases 1 to 5894)
  AUTHORS   Whitsett,J.A. and Lessard,J.L.
  TITLE     Characteristics of the microvillus brush border of human placenta:
            insulin receptor localization in brush border membranes
  JOURNAL   Endocrinology 103 (4), 1458-1468 (1978)
   PUBMED   758022
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB219527.1, BC096337.1,
            BX648462.1, CK824565.1, DA879845.1 and CF780766.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_004969.3.
            
            Summary: This gene encodes a zinc metallopeptidase that degrades
            intracellular insulin, and thereby terminates insulins activity, as
            well as participating in intercellular peptide signalling by
            degrading diverse peptides such as glucagon, amylin, bradykinin,
            and kallidin. The preferential affinity of this enzyme for insulin
            results in insulin-mediated inhibition of the degradation of other
            peptides such as beta-amyloid. Deficiencies in this protein's
            function are associated with Alzheimer's disease and type 2
            diabetes mellitus but mutations in this gene have not been shown to
            be causitive for these diseases. This protein localizes primarily
            to the cytoplasm but in some cell types localizes to the
            extracellular space, cell membrane, peroxisome, and mitochondrion.
            Alternative splicing results in multiple transcript variants
            encoding distinct isoforms. Additional transcript variants have
            been described but have not been experimentally verified.[provided
            by RefSeq, Sep 2009].
            
            Transcript Variant: This variant (1) encodes the longest protein
            (isoform 1). Alternative translation initiation of this transcript
            variant produces an isoform that lacks 41 aa from the N-terminus
            and, purportedly, lacks an N-terminal mitochondrial targeting
            sequence.
            
            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 :: SRR14038193.1209252.1,
                                           SRR14038194.3732127.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000265986.11/ ENSP00000265986.6
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-35                DB219527.1         3-37
            36-3165             BC096337.1         2-3131
            3166-4971           BX648462.1         3333-5138
            4972-5364           CK824565.1         174-566
            5365-5738           DA879845.1         122-495
            5739-5894           CF780766.1         284-439
FEATURES             Location/Qualifiers
     source          1..5894
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10q23.33"
     gene            1..5894
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /note="insulin degrading enzyme"
                     /db_xref="GeneID:3416"
                     /db_xref="HGNC:HGNC:5381"
                     /db_xref="MIM:146680"
     exon            1..172
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     CDS             75..3134
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /EC_number="3.4.24.56"
                     /note="isoform 1 is encoded by transcript variant 1;
                     insulinase; insulin protease; Abeta-degrading protease"
                     /codon_start=1
                     /product="insulin-degrading enzyme isoform 1"
                     /protein_id="NP_004960.2"
                     /db_xref="CCDS:CCDS7421.1"
                     /db_xref="GeneID:3416"
                     /db_xref="HGNC:HGNC:5381"
                     /db_xref="MIM:146680"
                     /translation="MRYRLAWLLHPALPSTFRSVLGARLPPPERLCGFQKKTYSKMNN
                     PAIKRIGNHITKSPEDKREYRGLELANGIKVLLISDPTTDKSSAALDVHIGSLSDPPN
                     IAGLSHFCEHMLFLGTKKYPKENEYSQFLSEHAGSSNAFTSGEHTNYYFDVSHEHLEG
                     ALDRFAQFFLCPLFDESCKDREVNAVDSEHEKNVMNDAWRLFQLEKATGNPKHPFSKF
                     GTGNKYTLETRPNQEGIDVRQELLKFHSAYYSSNLMAVCVLGRESLDDLTNLVVKLFS
                     EVENKNVPLPEFPEHPFQEEHLKQLYKIVPIKDIRNLYVTFPIPDLQKYYKSNPGHYL
                     GHLIGHEGPGSLLSELKSKGWVNTLVGGQKEGARGFMFFIINVDLTEEGLLHVEDIIL
                     HMFQYIQKLRAEGPQEWVFQECKDLNAVAFRFKDKERPRGYTSKIAGILHYYPLEEVL
                     TAEYLLEEFRPDLIEMVLDKLRPENVRVAIVSKSFEGKTDRTEEWYGTQYKQEAIPDE
                     VIKKWQNADLNGKFKLPTKNEFIPTNFEILPLEKEATPYPALIKDTAMSKLWFKQDDK
                     FFLPKACLNFEFFSPFAYVDPLHCNMAYLYLELLKDSLNEYAYAAELAGLSYDLQNTI
                     YGMYLSVKGYNDKQPILLKKIIEKMATFEIDEKRFEIIKEAYMRSLNNFRAEQPHQHA
                     MYYLRLLMTEVAWTKDELKEALDDVTLPRLKAFIPQLLSRLHIEALLHGNITKQAALG
                     IMQMVEDTLIEHAHTKPLLPSQLVRYREVQLPDRGWFVYQQRNEVHNNCGIEIYYQTD
                     MQSTSENMFLELFCQIISEPCFNTLRTKEQLGYIVFSGPRRANGIQGLRFIIQSEKPP
                     HYLESRVEAFLITMEKSIEDMTEEAFQKHIQALAIRRLDKPKKLSAECAKYWGEIISQ
                     QYNFDRDNTEVAYLKTLTKEDIIKFYKEMLAVDAPRRHKVSVHVLAREMDSCPVVGEF
                     PCQNDINLSQAPALPQPEVIQNMTEFKRGLPLFPLVKPHINFMAAKL"
     exon            173..357
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            358..565
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            566..735
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            736..858
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            859..971
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            972..1134
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            1135..1227
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            1228..1319
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            1320..1400
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            1401..1504
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            1505..1607
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            1608..1730
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            1731..1813
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            1814..1958
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            1959..2069
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            2070..2190
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            2191..2282
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            2283..2394
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            2395..2562
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            2563..2835
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            2836..2897
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            2898..2970
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            2971..3038
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     exon            3039..5894
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5312..5317
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /note="hexamer: AATAAA"
     polyA_site      5331
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /note="major polyA site"
     regulatory      5659..5664
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
                     /note="hexamer: AATAAA"
     polyA_site      5678
                     /gene="IDE"
                     /gene_synonym="INSULYSIN"
ORIGIN      
        1 atgcgcagtg cgcagggccg gctcgaagcg caagcaggaa gcgtttgcgg tgatcccggc
       61 gactgcgctg gctaatgcgg taccggctag cgtggcttct gcaccccgca ctgcccagca
      121 ccttccgctc agtcctcggc gcccgcctgc cgcctccgga gcgcctgtgt ggtttccaaa
      181 aaaagactta cagcaaaatg aataatccag ccatcaagag aataggaaat cacattacca
      241 agtctcctga agacaagcga gaatatcgag ggctagagct ggccaatggt atcaaagtac
      301 ttcttatcag tgatcccacc acggataagt catcagcagc acttgatgtg cacataggtt
      361 cattgtcgga tcctccaaat attgctggct taagtcattt ttgtgaacat atgctttttt
      421 tgggaacaaa gaaataccct aaagaaaatg aatacagcca gtttctcagt gagcatgcag
      481 gaagttcaaa tgcctttact agtggagagc ataccaatta ctattttgat gtttctcatg
      541 aacacctaga aggtgcccta gacaggtttg cacagttttt tctgtgcccc ttgttcgatg
      601 aaagttgcaa agacagagag gtgaatgcag ttgattcaga acatgagaag aatgtgatga
      661 atgatgcctg gagactcttt caattggaaa aagctacagg gaatcctaaa caccccttca
      721 gtaaatttgg gacaggtaac aaatatactc tggagactag accaaaccaa gaaggcattg
      781 atgtaagaca agagctactg aaattccatt ctgcttacta ttcatccaac ttaatggctg
      841 tttgtgtttt aggtcgagaa tctttagatg acttgactaa tctggtggta aagttatttt
      901 ctgaagtaga gaacaaaaat gttccattgc cagaatttcc tgaacaccct ttccaagaag
      961 aacatcttaa acaactttac aaaatagtac ccattaaaga tattaggaat ctctatgtga
     1021 catttcccat acctgacctt cagaaatact acaaatcaaa tcctggtcat tatcttggtc
     1081 atctcattgg gcatgaaggt cctggaagtc tgttatcaga acttaagtca aagggctggg
     1141 ttaatactct tgttggtggg cagaaggaag gagcccgagg ttttatgttt tttatcatta
     1201 atgtggactt gaccgaggaa ggattattac atgttgaaga tataattttg cacatgtttc
     1261 aatacattca gaagttacgt gcagaaggac ctcaagaatg ggttttccaa gagtgcaagg
     1321 acttgaatgc tgttgctttt aggtttaaag acaaagagag gccacggggc tatacatcta
     1381 agattgcagg aatattgcat tattatcccc tagaagaggt gctcacagcg gaatatttac
     1441 tggaagaatt tagacctgac ttaatagaga tggttctcga taaactcaga ccagaaaatg
     1501 tccgggttgc catagtttct aaatcttttg aaggaaaaac tgatcgcaca gaagagtggt
     1561 atggaaccca gtacaaacaa gaagctatac cggatgaagt catcaagaaa tggcaaaatg
     1621 ctgacctgaa tgggaaattt aaacttccta caaagaatga atttattcct acgaattttg
     1681 agattttacc gttagaaaaa gaggcgacac cataccctgc tcttattaag gatacagcta
     1741 tgagcaaact ttggttcaaa caagatgata agtttttttt gccgaaggct tgtctcaact
     1801 ttgaattttt cagcccattt gcttatgtgg accccttgca ctgtaacatg gcctatttgt
     1861 accttgagct cctcaaagac tcactcaacg agtatgcata tgcagcagag ctagcaggct
     1921 tgagctatga tctccaaaat accatctatg ggatgtatct ttcagtgaaa ggttacaatg
     1981 acaagcagcc aattttacta aagaagatta ttgagaaaat ggctaccttt gagattgatg
     2041 aaaaaagatt tgaaattatc aaagaagcat atatgcgatc tcttaacaat ttccgggctg
     2101 aacagcctca ccagcatgcc atgtactacc tccgcttgct gatgactgaa gtggcctgga
     2161 ctaaagatga gttaaaagaa gctctggatg atgtaaccct tcctcgcctt aaggccttca
     2221 tacctcagct cctgtcacgg ctgcacattg aagcccttct ccatggaaac ataacaaagc
     2281 aggctgcatt aggaattatg cagatggttg aagacaccct cattgaacat gctcatacca
     2341 aacctctcct tccaagtcag ctggttcggt atagagaagt tcagctccct gacagaggat
     2401 ggtttgttta tcagcagaga aatgaagttc acaataactg tggcatcgag atatactacc
     2461 aaacagacat gcaaagcacc tcagagaata tgtttctgga gctcttctgt cagattatct
     2521 cggaaccttg cttcaacacc ctgcgcacca aggagcagtt gggctatatc gtcttcagcg
     2581 ggccacgtcg agctaatggc atacagggct tgagattcat catccagtca gaaaagccac
     2641 ctcactacct agaaagcaga gtggaagctt tcttaattac catggaaaag tccatagagg
     2701 acatgacaga agaggccttc caaaaacaca ttcaggcatt agcaattcgt cgactagaca
     2761 aaccaaagaa gctatctgct gagtgtgcta aatactgggg agaaatcatc tcccagcaat
     2821 ataattttga cagagataac actgaggttg catatttaaa gacacttacc aaggaagata
     2881 tcatcaaatt ctacaaggaa atgttggcag tagatgctcc aaggagacat aaggtatccg
     2941 tccatgttct tgccagggaa atggattctt gtcctgttgt tggagagttc ccatgtcaaa
     3001 atgacataaa tttgtcacaa gcaccagcct tgccacaacc tgaagtgatt cagaacatga
     3061 ccgaattcaa gcgtggtctg ccactgtttc cccttgtgaa accacatatt aacttcatgg
     3121 ctgcaaaact ctgaagattc cccatgcatg ggaaagtgca agtggatgca ttcctgagtc
     3181 ttccagagcc taagaaaatc atcttggcca ctttaatagt ttctgattca ctattagaga
     3241 aacaaacaaa aaattgtcaa atgtcattat gtagaaatat tataaatcca aagtaaatta
     3301 caaaatctta tagatgtaga atatttttta aatacatgcc tcttaaatat tttaaaattt
     3361 ttcttttgat tactgagaga aatttcccca atataacaat gcttaaaatg aatgatattc
     3421 ctatagaatc ttccttccct attctgtaaa atagtcactt gtccgaagaa agttaaaagt
     3481 tagctctttt ctaaaagcct cctagcttga catagaaggc ttcacaacat ttagaaaggt
     3541 aataactttt taaaaattga tcctcaaatt tgctttctac ttgatggttt catgtaaatc
     3601 agtggaaaac attacatttg gcagatgata aagcaatgtc atcttttatt agtgaaatgc
     3661 tggttatata aggcatggtt ttaatctttt tataaaattt gaacatgttt tttatgccaa
     3721 ctcgtaaaat gctagaaaac cctacttatt tacaatgcta gaaatacaga cttaccttac
     3781 atcaattttg tcctaaaccg aatttctcag gattactgtg gtttctttca ttctgattga
     3841 attatattga cctacttctt catagttggt ttgcagtgtt ccatgagttt tacttttcct
     3901 catcaacata ttgctttaac acaacatatt tatttaacac gtacaaatag ggtcaacttc
     3961 agatcctact gagtgtgtga catgcttttc caacatcagc tttttgtaac cacctgtata
     4021 actttttatt acagtgaaat tgcagtcagt atgtgaacca aaatatcttg cccctttatg
     4081 aatttaaaag gcagccaata caaagccacc tttttggaaa tataaaaagt aaagccttgc
     4141 attcttatat agcaggtctt cataaaactc taaaatccct tgttgctacc agtctaatct
     4201 tgccttaaat gttaagttat tttttgaata tataaatata aacatataaa cacagatgat
     4261 gactggagta gacttttaaa aaaatatttt tttcatgaga tactatttta ggtgaaattg
     4321 ttactgtaga tttaacagct gttttgaaat atttactgtt attaaaactt gcttcaagag
     4381 aaattgtgaa tatatttcca tatacaagca ctagtaacag taagtggccc tgtcatccac
     4441 taactcaggc aaagtaaaga atggcatttt tgaaggacat tttacctccc catatgattt
     4501 gattggctag gactttcttc tgtaaagtca taccttttca catcttaagt ttttacattt
     4561 gccattttcc aaatctcaat tttgggcaag aacgatatag tcacaactat ggggctgctt
     4621 tcaaaagcgg ggctccattt ctactgtcag atcaatgtgg tgctgtaacc atctttttat
     4681 ccctaccttc aagaacctcc ttatatgaag cctgtcttta tccatcagaa ggtgtgtgaa
     4741 atcatcactt ccttctggtt ttatgtattt gtagactatg cagcttttca ttaaactgca
     4801 agtatataca agacagatct gaaattaggc ctgagtgttc cgatccacca ctgtactagt
     4861 aaataaaaat ccacctacct tttatgtgga aaattatgtg ctattgagta acttttagct
     4921 cttttttaaa aaatgggtga aatttaagtg tcttttttat gagaatgaca catgaagaga
     4981 tctgagagca atctcatgta gtcttccatg aacctgcaat tgtttggtat gcgtcagcat
     5041 tttccaattt ccaggttgga tctagagctg ctgttgatca ctcaggcata ctaatggatt
     5101 catttagatg ggtccaagct gcagtccatg agcaataaca gactacccca gatactgcag
     5161 tttacgcagt gcttagtaaa tgagatttgt ggaactaagt tattagttac ctgaggcttc
     5221 ttaagaaagt cttctttttt gaccagttga tgtgaaagag ggagcatgtg acacagccag
     5281 tatggtggag tgctagggtt atcctgttta caataaatcg cctgaatttc acctctggag
     5341 tctgcatttg tattattttt ccagttttag tgaaatagta cagtggccag tcctcagcct
     5401 acctctcaac atcccagttt gaccagattt cttgctttca ttgttcataa tgcagaaagc
     5461 agtgaattat attaacattt taaaagtgtt tctgggtaac aatgattttt gtcaaataga
     5521 agactcaatt tcacaacctt aagaatagat cacttttgta aaacaagaat ctcagtattt
     5581 gatgttggac tccttgctgt gagtattgtc actgactcca aacccagaaa gatttgttcc
     5641 tgcccttaca gggatgaaaa taaaaaggat agaaaaaata tttctctcct ctacaatgag
     5701 tccttacatc ttcttgccac atctccagct gcagtttagg cagatatctt gttcaatctc
     5761 tgtcttcttg atccctgtca aaataatttt tctactcata tagtggccag ttggctcagg
     5821 caggcatttc aagaggaatc tgcttgttcc tcacttttcc agcataggac agtggtccag
     5881 cccgcacagt cagc
//
