LOCUS       NM_015525               6040 bp    mRNA    linear   PRI 02-APR-2024
DEFINITION  Homo sapiens inhibitor of Bruton tyrosine kinase (IBTK), transcript
            variant 1, mRNA.
ACCESSION   NM_015525 XM_371835
VERSION     NM_015525.4
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 6040)
  AUTHORS   Vecchio,E., Nistico,N., Golino,G., Iaccino,E., Maisano,D.,
            Mimmi,S., Aloisio,A., Renna,M., Avagliano,A., Arcucci,A., Fiume,G.
            and Quinto,I.
  TITLE     IBtkalpha Activates the beta-Catenin-Dependent Transcription of MYC
            through Ubiquitylation and Proteasomal Degradation of GSK3beta in
            Cancerous B Cells
  JOURNAL   Int J Mol Sci 23 (4), 2044 (2022)
   PUBMED   35216159
  REMARK    GeneRIF: IBtkalpha Activates the beta-Catenin-Dependent
            Transcription of MYC through Ubiquitylation and Proteasomal
            Degradation of GSK3beta in Cancerous B Cells.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 6040)
  AUTHORS   Albano,F., Chiurazzi,F., Mimmi,S., Vecchio,E., Pastore,A.,
            Cimmino,C., Frieri,C., Iaccino,E., Pisano,A., Golino,G., Fiume,G.,
            Mallardo,M., Scala,G. and Quinto,I.
  TITLE     The expression of inhibitor of bruton's tyrosine kinase gene is
            progressively up regulated in the clinical course of chronic
            lymphocytic leukaemia conferring resistance to apoptosis
  JOURNAL   Cell Death Dis 9 (1), 13 (2018)
   PUBMED   29317636
  REMARK    GeneRIF: RNA interference of Inhibitor of brutons tyrosine
            kinase-isoform alpha up regulated the expression of pro-apoptotic
            genes, including TNF, CRADD, CASP7, BNIP3 and BIRC3 and is a novel
            marker of CLL progression promoting cell growth and resistance to
            apoptosis.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 6040)
  AUTHORS   Willy,J.A., Young,S.K., Mosley,A.L., Gawrieh,S., Stevens,J.L.,
            Masuoka,H.C. and Wek,R.C.
  TITLE     Function of inhibitor of Bruton's tyrosine kinase isoform alpha
            (IBTKalpha) in nonalcoholic steatohepatitis links autophagy and the
            unfolded protein response
  JOURNAL   J Biol Chem 292 (34), 14050-14065 (2017)
   PUBMED   28710282
  REMARK    GeneRIF: Data suggest that IBTKalpha is (a) localized in
            hepatocytes in endoplasmic reticulum (ER), (b) associates with
            specific proteins (LC3b, SEC16A, SEC31A), and (c) plays role in
            autophagy. Progression of nonalcoholic fatty liver disease is
            associated with changes in liver: (a) up-regulation of expression
            of IBTKalpha, (b) unfolded protein response, (c) ER stress, and (d)
            inhibition of autophagy.
REFERENCE   4  (bases 1 to 6040)
  AUTHORS   Fiume,G., Scialdone,A., Rizzo,F., De Filippo,M.R., Laudanna,C.,
            Albano,F., Golino,G., Vecchio,E., Pontoriero,M., Mimmi,S.,
            Ceglia,S., Pisano,A., Iaccino,E., Palmieri,C., Paduano,S.,
            Viglietto,G., Weisz,A., Scala,G. and Quinto,I.
  TITLE     IBTK Differently Modulates Gene Expression and RNA Splicing in HeLa
            and K562 Cells
  JOURNAL   Int J Mol Sci 17 (11), 1848 (2016)
   PUBMED   27827994
  REMARK    GeneRIF: The results indicate that IBTKa differently modulates gene
            expression and RNA splicing in HeLa and K562 cells, demonstrating a
            novel biological role of this protein.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 6040)
  AUTHORS   Pisano,A., Ceglia,S., Palmieri,C., Vecchio,E., Fiume,G., de
            Laurentiis,A., Mimmi,S., Falcone,C., Iaccino,E., Scialdone,A.,
            Pontoriero,M., Masci,F.F., Valea,R., Krishnan,S., Gaspari,M.,
            Cuda,G., Scala,G. and Quinto,I.
  TITLE     CRL3IBTK Regulates the Tumor Suppressor Pdcd4 through
            Ubiquitylation Coupled to Proteasomal Degradation
  JOURNAL   J Biol Chem 290 (22), 13958-13971 (2015)
   PUBMED   25882842
  REMARK    GeneRIF: CRL3(IBTK) is a novel ubiquitin ligase with regulatory
            roles in cellular pathways, such as the Pdcd4-dependent translation
            of mRNAs
REFERENCE   6  (bases 1 to 6040)
  AUTHORS   Ramalho,V.D., Oliveira Junior,E.B., Tani,S.M., Roxo Junior,P. and
            Vilela,M.M.
  TITLE     Mutations of Bruton's tyrosine kinase gene in Brazilian patients
            with X-linked agammaglobulinemia
  JOURNAL   Braz J Med Biol Res 43 (9), 910-913 (2010)
   PUBMED   20721470
  REMARK    GeneRIF: three novel (Ala347fsX55, I355T, and Thr324fsX24)
            mutations in Bruton's tyrosine kinase in patients with X-linked
            agammaglobulinemia
REFERENCE   7  (bases 1 to 6040)
  AUTHORS   Fiume,G., Rossi,A., Di Salle,E., Spatuzza,C., Mallardo,M., Scala,G.
            and Quinto,I.
  TITLE     Computational analysis and in vivo validation of a microRNA encoded
            by the IBTK gene, a regulator of B-lymphocytes differentiation and
            survival
  JOURNAL   Comput Biol Chem 33 (6), 434-439 (2009)
   PUBMED   19782003
  REMARK    GeneRIF: The IBTK gene encodes the proteins IBtk-alpha, beta and
            gamma that regulate the B cell receptor signalling through Bruton's
            tyrosine kinase, which promotes B cell survival and
            differentiation.
REFERENCE   8  (bases 1 to 6040)
  AUTHORS   Spatuzza,C., Schiavone,M., Di Salle,E., Janda,E., Sardiello,M.,
            Fiume,G., Fierro,O., Simonetta,M., Argiriou,N., Faraonio,R.,
            Capparelli,R., Quinto,I. and Scala,G.
  TITLE     Physical and functional characterization of the genetic locus of
            IBtk, an inhibitor of Bruton's tyrosine kinase: evidence for three
            protein isoforms of IBtk
  JOURNAL   Nucleic Acids Res 36 (13), 4402-4416 (2008)
   PUBMED   18596081
  REMARK    GeneRIF: Identification of three IBTKalpha, IBTKbeta and IBTKgamma
            mRNAs, whose transcription is driven by two distinct promoter
            regions.
REFERENCE   9  (bases 1 to 6040)
  AUTHORS   Mungall,A.J., Palmer,S.A., Sims,S.K., Edwards,C.A., Ashurst,J.L.,
            Wilming,L., Jones,M.C., Horton,R., Hunt,S.E., Scott,C.E.,
            Gilbert,J.G., Clamp,M.E., Bethel,G., Milne,S., Ainscough,R.,
            Almeida,J.P., Ambrose,K.D., Andrews,T.D., Ashwell,R.I.,
            Babbage,A.K., Bagguley,C.L., Bailey,J., Banerjee,R., Barker,D.J.,
            Barlow,K.F., Bates,K., Beare,D.M., Beasley,H., Beasley,O.,
            Bird,C.P., Blakey,S., Bray-Allen,S., Brook,J., Brown,A.J.,
            Brown,J.Y., Burford,D.C., Burrill,W., Burton,J., Carder,C.,
            Carter,N.P., Chapman,J.C., Clark,S.Y., Clark,G., Clee,C.M.,
            Clegg,S., Cobley,V., Collier,R.E., Collins,J.E., Colman,L.K.,
            Corby,N.R., Coville,G.J., Culley,K.M., Dhami,P., Davies,J.,
            Dunn,M., Earthrowl,M.E., Ellington,A.E., Evans,K.A., Faulkner,L.,
            Francis,M.D., Frankish,A., Frankland,J., French,L., Garner,P.,
            Garnett,J., Ghori,M.J., Gilby,L.M., Gillson,C.J., Glithero,R.J.,
            Grafham,D.V., Grant,M., Gribble,S., Griffiths,C., Griffiths,M.,
            Hall,R., Halls,K.S., Hammond,S., Harley,J.L., Hart,E.A.,
            Heath,P.D., Heathcott,R., Holmes,S.J., Howden,P.J., Howe,K.L.,
            Howell,G.R., Huckle,E., Humphray,S.J., Humphries,M.D., Hunt,A.R.,
            Johnson,C.M., Joy,A.A., Kay,M., Keenan,S.J., Kimberley,A.M.,
            King,A., Laird,G.K., Langford,C., Lawlor,S., Leongamornlert,D.A.,
            Leversha,M., Lloyd,C.R., Lloyd,D.M., Loveland,J.E., Lovell,J.,
            Martin,S., Mashreghi-Mohammadi,M., Maslen,G.L., Matthews,L.,
            McCann,O.T., McLaren,S.J., McLay,K., McMurray,A., Moore,M.J.,
            Mullikin,J.C., Niblett,D., Nickerson,T., Novik,K.L., Oliver,K.,
            Overton-Larty,E.K., Parker,A., Patel,R., Pearce,A.V., Peck,A.I.,
            Phillimore,B., Phillips,S., Plumb,R.W., Porter,K.M., Ramsey,Y.,
            Ranby,S.A., Rice,C.M., Ross,M.T., Searle,S.M., Sehra,H.K.,
            Sheridan,E., Skuce,C.D., Smith,S., Smith,M., Spraggon,L.,
            Squares,S.L., Steward,C.A., Sycamore,N., Tamlyn-Hall,G., Tester,J.,
            Theaker,A.J., Thomas,D.W., Thorpe,A., Tracey,A., Tromans,A.,
            Tubby,B., Wall,M., Wallis,J.M., West,A.P., White,S.S.,
            Whitehead,S.L., Whittaker,H., Wild,A., Willey,D.J., Wilmer,T.E.,
            Wood,J.M., Wray,P.W., Wyatt,J.C., Young,L., Younger,R.M.,
            Bentley,D.R., Coulson,A., Durbin,R., Hubbard,T., Sulston,J.E.,
            Dunham,I., Rogers,J. and Beck,S.
  TITLE     The DNA sequence and analysis of human chromosome 6
  JOURNAL   Nature 425 (6960), 805-811 (2003)
   PUBMED   14574404
REFERENCE   10 (bases 1 to 6040)
  AUTHORS   Liu,W., Quinto,I., Chen,X., Palmieri,C., Rabin,R.L., Schwartz,O.M.,
            Nelson,D.L. and Scala,G.
  TITLE     Direct inhibition of Bruton's tyrosine kinase by IBtk, a
            Btk-binding protein
  JOURNAL   Nat Immunol 2 (10), 939-946 (2001)
   PUBMED   11577348
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DQ005633.1 and BM670666.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_015525.3.
            
            Summary: Bruton tyrosine kinase (BTK) is a protein tyrosine kinase
            that is expressed in B cells, macrophages, and neutrophils. The
            protein encoded by this gene binds to BTK and downregulates BTK's
            kinase activity. In addition, the encoded protein disrupts
            BTK-mediated calcium mobilization and negatively regulates the
            activation of nuclear factor-kappa-B-driven transcription. This
            gene has a pseudogene on chromosome 18. Alternative splicing
            results in multiple transcript variants encoding distinct isoforms.
            [provided by RefSeq, Jul 2014].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer 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 :: DQ005633.1, SRR18074969.3659932.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000306270.12/ ENSP00000305721.7
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-5788              DQ005633.1         11-5798
            5789-6040           BM670666.1         17-268              c
FEATURES             Location/Qualifiers
     source          1..6040
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q14.1"
     gene            1..6040
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /note="inhibitor of Bruton tyrosine kinase"
                     /db_xref="GeneID:25998"
                     /db_xref="HGNC:HGNC:17853"
                     /db_xref="MIM:606457"
     exon            1..183
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            184..861
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     CDS             541..4602
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /note="isoform 1 is encoded by transcript variant 1;
                     BTK-binding protein; Bruton agammaglobulinemia tyrosine
                     kinase inhibitor; inhibitor of Bruton's tyrosine
                     kinase-alpha; inhibitor of Bruton's tyrosine kinase-beta;
                     inhibitor of Bruton's tyrosine kinase-gamma"
                     /codon_start=1
                     /product="inhibitor of Bruton tyrosine kinase isoform 1"
                     /protein_id="NP_056340.2"
                     /db_xref="CCDS:CCDS34490.1"
                     /db_xref="GeneID:25998"
                     /db_xref="HGNC:HGNC:17853"
                     /db_xref="MIM:606457"
                     /translation="MSSPMPDCTSKCRSLKHALDVLSVVTKGSENQIKAFLSSHCYNA
                     ATIKDVFGRNALHLVSSCGKKGVLDWLIQKGVDLLVKDKESGWTALHRSIFYGHIDCV
                     WSLLKHGVSLYIQDKEGLSALDLVMKDRPTHVVFKNTDPTDVYTWGDNTNFTLGHGSQ
                     NSKHHPELVDLFSRSGIYIKQVVLCKFHSVFLSQKGQVYTCGHGPGGRLGHGDEQTCL
                     VPRLVEGLNGHNCSQVAAAKDHTVVLTEDGCVYTFGLNIFHQLGIIPPPSSCNVPRQI
                     QAKYLKGRTIIGVAAGRFHTVLWTREAVYTMGLNGGQLGCLLDPNGEKCVTAPRQVSA
                     LHHKDIALSLVAASDGATVCVTTRGDIYLLADYQCKKMASKQLNLKKVLVSGGHMEYK
                     VDPEHLKENGGQKICILAMDGAGRVFCWRSVNSSLKQCRWAYPRQVFISDIALNRNEI
                     LFVTQDGEGFRGRWFEEKRKSSEKKEILSNLHNSSSDVSYVSDINSVYERIRLEKLTF
                     AHRAVSVSTDPSGCNFAILQSDPKTSLYEIPAVSSSSFFEEFGKLLREADEMDSIHDV
                     TFQVGNRLFPAHKYILAVHSDFFQKLFLSDGNTSEFTDIYQKDEDSAGCHLFVVEKVH
                     PDMFEYLLQFIYTDTCDFLTHGFKPRIHLNKNPEEYQGTLNSHLNKVNFHEDDNQKSA
                     FEVYKSNQAQTVSERQKSKPKSCKKGKNIREDDPVRMLQTVAKKFDFSNLSSRLDGVR
                     FENEKINVIAKNTGNKLKLSQKKCSFLCDVTMKSVDGKEFPCHKCVLCARLEYFHSML
                     SSSWIEASSCAALEMPIHSDILKVILDYLYTDEAVVIKESQNVDFICSVLVVADQLLI
                     TRLKEICEVALTEKLTLKNAAMLLEFAAMYSAKQLKLSCLQFIGLNMAALLEARSLDV
                     LSDGVLKDLSEFYRKMIPAMDRRVITPYQDGPDISYLEVEDGDIFLKEEINMEQNHSE
                     TMFKKAKTKAKKKPRKRSDSSGGYNLSDIIQSPSSTGLLKSGKTNSVESLPELLTSDS
                     EGSYAGVGSPRDLQSPDFTTGFHSDKIEAKVKPYVNGTSPVYSREDLKPWEKSPILKI
                     SAPQPIPSNRIDTTSSASWVAGSFSPVSPPVVDLRTIMEIEESRQKCGATPKSHLGKT
                     VSHGVKLSQKQRKMIALTTKENNSGMNSMETVLFTPSKAPKPVNAWASSLHSVSSKSF
                     RDFLLEEKKSVTSHSSGDHVKKVSFKGIENSQAPKIVRCSTHGTPGPEGNHISDLPLL
                     DSPNPWLSSSVTAPSMVAPVTFASIVEEELQQEAALIRSREKPLALIQIEEHAIQDLL
                     VFYEAFGNPEEFVIVERTPQGPLAVPMWNKHGC"
     exon            862..958
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            959..1083
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            1084..1194
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            1195..1365
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            1366..1483
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            1484..1664
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            1665..1788
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            1789..1966
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            1967..2141
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            2142..2744
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            2745..2831
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            2832..2914
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            2915..2952
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            2953..3049
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            3050..3151
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            3152..3269
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            3270..3330
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            3331..3452
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            3453..3565
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            3566..3714
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            3715..3878
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            3879..3971
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            3972..4115
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            4116..4265
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            4266..4337
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            4338..4470
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     exon            4471..6040
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5763..5768
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /note="hexamer: AATAAA"
     polyA_site      5789
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /note="major polyA site"
     regulatory      6018..6023
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
                     /note="hexamer: AGTAAA"
     polyA_site      6040
                     /gene="IBTK"
                     /gene_synonym="BTBD26; BTKI"
ORIGIN      
        1 atccccgttc ccgattcctg tagtagcggc tgtattgcag ccgcctgccg aactgacccg
       61 ggtctgggga ctggcccctc tggcgccgtt cggtttctct tattgccttc actgaggatg
      121 agtccctttg tggctctatg tggaccctgc ggaatccacc ggcgcagttt catctagcga
      181 ctggtcaccc ttgcaattat ggatatttaa aagggtcaga cagtgtggag ggggagttcc
      241 cctcctcact cccccttggt gcttgactcc aggaataatt tataaactgt ggaatttttt
      301 taaatgaaga acttgtattt gatatgaact ttatagagct atttataatt tttttgattt
      361 aagtgccaaa aaattgtata aagatatata gttttatact attgtcagga ggatttaaat
      421 tatcctaaaa aggtaattta ttctctgtaa cttcctcaat agcacctttg tgtcctggct
      481 ttttcatttt ttaaaattag ttttcacgat tctgaagtaa gtggtataaa aacagttagg
      541 atgagttcac ccatgcctga ctgcacatca aagtgtcgat ccctgaagca tgctttggat
      601 gtcctttctg tggtaacaaa ggggagcgaa aaccagatta aggcctttct ctccagtcat
      661 tgttacaatg ctgcaactat caaggatgtt tttggcagga atgccctcca ccttgtttcc
      721 tcctgtggaa agaaaggagt gttagattgg cttattcaga aaggagtgga tctgttggtg
      781 aaagacaaag agtctggatg gacagcattg cacagaagca ttttttatgg acatattgat
      841 tgtgtttggt ctctattgaa gcatggtgtt agtctgtata ttcaagataa agaaggcttg
      901 tcagctttgg atcttgtaat gaaggataga ccaactcatg tagtattcaa gaatactgat
      961 cctacagatg tttatacttg gggcgataat acaaatttta ccctgggtca tggaagccag
     1021 aatagcaaac atcatccaga gttggtggat ctgttctcca ggagtgggat ttatatcaag
     1081 caggtggtgc tttgtaaatt tcactccgtg tttctgtctc agaaagggca ggtttatacc
     1141 tgtggtcatg gtcctggagg gcgattagga catggagatg aacagacatg cttggtccct
     1201 cggcttgtgg aaggactgaa tggtcataat tgttcccaag tggcagctgc taaggatcat
     1261 actgttgtat taactgaaga tggatgtgtt tatacatttg gtctaaacat ttttcatcaa
     1321 ttaggaatta ttccaccgcc ttccagttgt aatgtaccca gacagataca ggcaaaatat
     1381 ctgaaaggaa ggacaatcat tggcgttgca gcaggcaggt ttcatacagt cctatggact
     1441 agagaagctg tttacactat gggactaaat ggtggacaac tgggttgttt gctagatccc
     1501 aatggagaaa agtgtgtaac tgctcctcgt caggtctctg cccttcacca taaagacatt
     1561 gctctgtctt tggttgctgc aagtgatgga gctacagtct gtgttaccac aaggggagat
     1621 atttacttac ttgcagacta tcagtgcaag aagatggctt ctaaacagtt gaacttgaaa
     1681 aaagttcttg tgtctggggg tcatatggaa tacaaggttg atcctgaaca tttgaaagaa
     1741 aatgggggtc aaaaaatttg cattcttgca atggatggag ctggaagggt gttttgctgg
     1801 agatcagtca acagttctct gaagcagtgt cgatgggcct atccacgtca ggtcttcatt
     1861 tctgatattg ctttaaatag aaatgaaatt ctatttgtta cgcaagatgg agaaggattt
     1921 agagggagat ggtttgaaga gaaaagaaag agttctgaaa agaaagagat tttatcaaac
     1981 cttcacaatt cctcatcaga tgtgtcttat gtctctgata taaatagtgt gtatgaaaga
     2041 attcgacttg agaaacttac ctttgcacat agagctgtta gtgtcagcac agatccaagt
     2101 ggatgcaact ttgcaatcct gcagtcagat cctaaaacaa gcctttatga aattccagct
     2161 gtgtcctcat catccttttt tgaagagttt ggcaaactgt tgagggaagc agatgaaatg
     2221 gacagcattc atgatgtgac atttcaagtt ggcaatagac tcttccctgc acataaatat
     2281 attttggcag tgcattctga tttttttcag aaattgtttc tttcagatgg taatacttca
     2341 gaatttacag atatttacca gaaagatgaa gattctgcag ggtgccatct ctttgtggta
     2401 gagaaggttc atcctgacat gtttgaatac cttttacaat ttatatacac agatacttgt
     2461 gactttttaa ctcatggctt caaaccaaga atacacttaa acaaaaaccc agaagaatat
     2521 cagggaactc tgaattctca tttgaataaa gtgaatttcc atgaagatga taaccagaag
     2581 tctgcatttg aagtttacaa aagtaatcaa gctcaaacag ttagtgagag gcagaagagc
     2641 aaacctaaat cttgtaaaaa aggaaaaaat attagggaag atgatcctgt aagaatgttg
     2701 caaactgttg caaagaaatt cgacttcagt aatttgagta gtaggttaga tggagtcaga
     2761 tttgaaaatg aaaaaattaa tgttattgcc aagaacactg gtaataaact gaagctaagt
     2821 cagaaaaaat gttcatttct gtgtgacgtg accatgaaat cagtggatgg aaaggaattt
     2881 ccttgtcata aatgtgttct ttgtgctaga cttgaatatt ttcatagtat gctgagtagc
     2941 tcatggattg aggcttccag ttgtgcagct ctggaaatgc caatacattc tgatatatta
     3001 aaagttattt tggactacct ctatactgat gaagctgtgg tgataaaaga atctcaaaat
     3061 gtagatttta tttgtagtgt tcttgtggtg gctgatcaac ttctcataac ccggttgaaa
     3121 gagatttgtg aagtagcatt aactgaaaaa cttaccctga agaatgctgc tatgctactg
     3181 gaatttgcag caatgtatag tgcaaaacag ttgaaactgt cttgtttaca gtttatagga
     3241 ttgaatatgg cagctttact tgaagcaagg tctcttgatg ttttaagcga tggtgttttg
     3301 aaggatcttt ctgagtttta ccggaaaatg attccagcaa tggatagaag agtcattaca
     3361 ccatatcaag atggaccaga tattagctat ttggaagtag aagatggaga tatcttcttg
     3421 aaagaagaaa taaatatgga acaaaatcat tcggaaacta tgttcaagaa agcaaaaaca
     3481 aaagctaaaa agaagccacg taaacgttca gatagttctg gaggttataa cctttcagat
     3541 attattcaga gtccatcatc tacaggatta ttaaagtctg gtaagaccaa ttctgtggaa
     3601 tctcttccag aactgttgac atcagactct gaaggaagct atgcaggagt gggtagtcct
     3661 agagatttac agtcccctga tttcacaaca ggatttcatt cagataagat tgaggcgaaa
     3721 gtcaaaccgt atgttaatgg tacatctcct gtgtattcta gggaagattt aaaaccatgg
     3781 gaaaagtcac caatacttaa aatatctgct ccacagccta ttcccagtaa cagaattgat
     3841 actaccagct ctgccagttg ggttgctggt tctttcagtc ctgtcagccc tcctgttgtg
     3901 gatctcagaa ctatcatgga aatagaagaa agtagacaaa aatgtggagc tacaccaaag
     3961 tcacatttag gcaaaacagt ttctcatgga gttaaacttt ctcagaagca acgaaaaatg
     4021 attgcattga ctaccaagga aaacaattca ggaatgaata gcatggaaac agttttattc
     4081 actccttcaa aagcccccaa accagtgaat gcatgggcat cttctctgca ttcagtttca
     4141 tccaagtcat tccgggattt cttactagaa gaaaaaaagt ctgttactag ccatagttca
     4201 ggcgatcatg tcaaaaaagt ttcttttaaa ggaattgaaa attctcaggc accaaaaatt
     4261 gtcagatgct ctacccatgg taccccagga ccagaaggca accatatttc agatttacca
     4321 cttctagaca gtcccaatcc ctggctatct tcttcagtga ctgctccatc catggtagcc
     4381 ccagtcactt ttgcatctat tgtagaagaa gaactacaac aagaagcagc tcttattaga
     4441 agtcgagaaa aaccgttggc tctgattcag attgaggagc atgccataca agatttattg
     4501 gttttctatg aggcatttgg caaccctgaa gagtttgtca ttgttgaaag gacaccgcag
     4561 ggaccactgg cagtacctat gtggaataag catggatgct agttcactgt ggagttgaga
     4621 tgcattttac ataattatga gtttgttcat ataaagaaaa gctgtggaaa agagtcttag
     4681 agattttgta atatcattct aaatagatta agaaaagata taatttcttt actgcagtta
     4741 aatcatataa tgtttgtatg attaaaaata aatttctcag aattgtgatt ttagtaactt
     4801 tatataaaat gtgtgagaca aaaacttatt aaggttaaat agaattgttt cttctgaata
     4861 atctaacaaa ggaaaatata agtgattgaa tcataagata taaggggggt aaagtattaa
     4921 aaataacttt tttgtttgat aacttgagaa tttagaagat tttgccaagt atgtgttgtt
     4981 gcttgacttc ttaaatatgg cattgatgaa tttaaagtag gagcatcagt tattacttct
     5041 gattcattaa tggccagaat tttgtgtttg gtgtaatagt tgtgtcacca ttcttgttgc
     5101 tttttaaaaa tcaggctaat catgtggtcc atgtctcttc aaagcttgac ctgcacaaat
     5161 gccatatttc tatttggacc acatattctc cattttgcat tgagcagtag agtacagtgg
     5221 aaagggaata agaatactga ttattctgaa cagtttagtc ccaagagaat agcgttttaa
     5281 aaaagaaaaa caagatttgg agtcattgtg ggttattttt ggtgggatgg aggatcttaa
     5341 aaatgcctaa ttgtgagaga atcaattgct gaaagtgtta aaatttctga aaataaatgc
     5401 ttaattacat atacaggaat taaatagttt ggaagagggt tggattatca ttacctttac
     5461 aatactgtat aatcagaagt tctctgaacc tcaattgtat atctagacat aaaaattgtt
     5521 ttctgtatag gatgttgttt ggtttgtttc tgagtgttta aattttgcaa aaacaaatgt
     5581 taaatttgtg cttcagtacc tagataaatt ggaaaggtta atgttctagt ttctggaagg
     5641 taagcctggg agacacataa gcaattcact gctataattt agttgatgta aaatgacgga
     5701 aactgactca atatgtcagg tttaactctg cccaaaagca gcagacatgt aagcagatgt
     5761 gcaataaaaa atgatcttga tccatttcac taatgtgtgc ttgacatttt ttactatatt
     5821 gacatttatt atggaaagag ttaataatta ttttttctga tgtgctacac tagtggccag
     5881 tatatggtta agttgatgct gtatttattc taagacggat ttaaaaaggc agttttctaa
     5941 atatgaactt gtgaattttt gtatgtgtgt ttgagtaaat tgagaaatga attttataaa
     6001 tgttctattg atgttgcagt aaagaagcct tttgaagtaa
//
