LOCUS       NM_004379              10095 bp    mRNA    linear   PRI 11-FEB-2025
DEFINITION  Homo sapiens cAMP responsive element binding protein 1 (CREB1),
            transcript variant 1, mRNA.
ACCESSION   NM_004379
VERSION     NM_004379.5
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 10095)
  AUTHORS   He,C., Zeng,Z., Yang,Y., Ye,S., Wu,Q., Liu,X., Liu,C., Zeng,W. and
            Liu,S.
  TITLE     Silencing of CircTRIM25/miR-138-5p/CREB1 axis promotes
            chondrogenesis in osteoarthritis
  JOURNAL   Autoimmunity 57 (1), 2361749 (2024)
   PUBMED   39007896
  REMARK    GeneRIF: Silencing of CircTRIM25/miR-138-5p/CREB1 axis promotes
            chondrogenesis in osteoarthritis.
            Erratum:[Autoimmunity. 2024 Dec;57(1):2435720. doi:
            10.1080/08916934.2024.2435720.. PMID: 39621026]
REFERENCE   2  (bases 1 to 10095)
  AUTHORS   Aida,Y. and Kataoka,K.
  TITLE     CREB activates the MafA promoter through proximal E-boxes and a
            CCAAT motif in pancreatic beta-cells
  JOURNAL   J Mol Endocrinol 73 (3), e240023 (2024)
   PUBMED   39189982
  REMARK    GeneRIF: CREB activates the MafA promoter through proximal E-boxes
            and a CCAAT motif in pancreatic beta-cells.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 10095)
  AUTHORS   Ismael,A., Robinette,A.J., Huric,L., Schuetz,J., Dona,K.,
            Benson,D., Cocucci,E. and Cottini,F.
  TITLE     CREB1 promotes expression of immune checkpoint HLA-E leading to
            immune escape in multiple myeloma
  JOURNAL   Leukemia 38 (8), 1777-1786 (2024)
   PUBMED   38902472
  REMARK    GeneRIF: CREB1 promotes expression of immune checkpoint HLA-E
            leading to immune escape in multiple myeloma.
REFERENCE   4  (bases 1 to 10095)
  AUTHORS   Pei,W., Yin,W., Yu,T., Zhang,X., Zhang,Q., Yang,X., Shi,C., Shen,W.
            and Liu,G.
  TITLE     Dual-Specificity Phosphatase 4 Promotes Malignant Features in
            Colorectal Cancer Through Cyclic-AMP Response Element Binding
            Protein/Protein Kinase CAMP-Activated Catalytic Subunit Beta
            Activation
  JOURNAL   Dig Dis Sci 69 (8), 2856-2874 (2024)
   PUBMED   38824257
  REMARK    GeneRIF: Dual-Specificity Phosphatase 4 Promotes Malignant Features
            in Colorectal Cancer Through Cyclic-AMP Response Element Binding
            Protein/Protein Kinase CAMP-Activated Catalytic Subunit Beta
            Activation.
REFERENCE   5  (bases 1 to 10095)
  AUTHORS   Ma,Y., Zong,H., Pan,P., Shang,H. and Yang,X.
  TITLE     The CREB1/WNK1 axis promotes the tumorigenesis of ovarian cancer
            via regulating HIF-1
  JOURNAL   Exp Cell Res 438 (1), 114006 (2024)
   PUBMED   38599542
  REMARK    GeneRIF: The CREB1/WNK1 axis promotes the tumorigenesis of ovarian
            cancer via regulating HIF-1.
REFERENCE   6  (bases 1 to 10095)
  AUTHORS   Meyer,T.E. and Habener,J.F.
  TITLE     Cyclic AMP response element binding protein CREB and modulator
            protein CREM are products of distinct genes
  JOURNAL   Nucleic Acids Res 20 (22), 6106 (1992)
   PUBMED   1461747
REFERENCE   7  (bases 1 to 10095)
  AUTHORS   Zhao,L.J. and Giam,C.Z.
  TITLE     Human T-cell lymphotropic virus type I (HTLV-I) transcriptional
            activator, Tax, enhances CREB binding to HTLV-I 21-base-pair
            repeats by protein-protein interaction
  JOURNAL   Proc Natl Acad Sci U S A 89 (15), 7070-7074 (1992)
   PUBMED   1386673
REFERENCE   8  (bases 1 to 10095)
  AUTHORS   Rehfuss,R.P., Walton,K.M., Loriaux,M.M. and Goodman,R.H.
  TITLE     The cAMP-regulated enhancer-binding protein ATF-1 activates
            transcription in response to cAMP-dependent protein kinase A
  JOURNAL   J Biol Chem 266 (28), 18431-18434 (1991)
   PUBMED   1655749
REFERENCE   9  (bases 1 to 10095)
  AUTHORS   Short,M.L., Manohar,C.F., Furtado,M.R., Ghadge,G.D., Wolinsky,S.M.,
            Thimmapaya,B. and Jungmann,R.A.
  TITLE     Nucleotide and derived amino-acid sequences of the CRE-binding
            proteins from rat C6 glioma and HeLa cells
  JOURNAL   Nucleic Acids Res 19 (15), 4290 (1991)
   PUBMED   1831258
REFERENCE   10 (bases 1 to 10095)
  AUTHORS   Waeber,G., Meyer,T.E., Hoeffler,J.P. and Habener,J.F.
  TITLE     Diversification of cyclic AMP-responsive enhancer binding
            proteins-generated by alternative exon splicing
  JOURNAL   Trans Assoc Am Physicians 103, 28-37 (1990)
   PUBMED   1966745
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC095407.1, AC079767.7 and
            BU154326.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_004379.4.
            
            Summary: This gene encodes a transcription factor that is a member
            of the leucine zipper family of DNA binding proteins. This protein
            binds as a homodimer to the cAMP-responsive element, an octameric
            palindrome. The protein is phosphorylated by several protein
            kinases, and induces transcription of genes in response to hormonal
            stimulation of the cAMP pathway. Alternate splicing of this gene
            results in several transcript variants encoding different isoforms.
            [provided by RefSeq, Mar 2016].
            
            Transcript Variant: This variant (1, also known as A) lacks an
            alternate in-frame exon compared to variant 2. The resulting
            isoform (A) has the same N- and C-termini but is shorter compared
            to isoform B.
            
            Sequence Note: The RefSeq transcript and protein were derived from
            transcript and genomic sequence to make the sequence consistent
            with the reference genome assembly. The genomic coordinates used
            for the transcript record were based on alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803613.50553.1,
                                           SRR1660807.69906.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000353267.8/ ENSP00000236995.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2591              BC095407.1         15-2605
            2592-9831           AC079767.7         8439-15678
            9832-10095          BU154326.1         15-278              c
FEATURES             Location/Qualifiers
     source          1..10095
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q33.3"
     gene            1..10095
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /note="cAMP responsive element binding protein 1"
                     /db_xref="GeneID:1385"
                     /db_xref="HGNC:HGNC:2345"
                     /db_xref="MIM:123810"
     exon            1..173
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /inference="alignment:Splign:2.1.0"
     exon            174..295
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /inference="alignment:Splign:2.1.0"
     CDS             182..1165
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /note="isoform A is encoded by transcript variant 1;
                     cAMP-response element-binding protein-1; active
                     transcription factor CREB; transactivator protein; cyclic
                     AMP-responsive element-binding protein 1; cyclic adenosine
                     3',5'-monophosphate response element-binding protein CREB;
                     cyclic adenosine 3',5'-monophosphate response element
                     binding protein"
                     /codon_start=1
                     /product="cyclic AMP-responsive element-binding protein 1
                     isoform A"
                     /protein_id="NP_004370.1"
                     /db_xref="CCDS:CCDS2374.1"
                     /db_xref="GeneID:1385"
                     /db_xref="HGNC:HGNC:2345"
                     /db_xref="MIM:123810"
                     /translation="MTMESGAENQQSGDAAVTEAENQQMTVQAQPQIATLAQVSMPAA
                     HATSSAPTVTLVQLPNGQTVQVHGVIQAAQPSVIQSPQVQTVQISTIAESEDSQESVD
                     SVTDSQKRREILSRRPSYRKILNDLSSDAPGVPRIEEEKSEEETSAPAITTVTVPTPI
                     YQTSSGQYIAITQGGAIQLANNGTDGVQGLQTLTMTNAAATQPGTTILQYAQTTDGQQ
                     ILVPSNQVVVQAASGDVQTYQIRTAPTSTIAPGVVMASSPALPTQPAEEAARKREVRL
                     MKNREAARECRRKKKEYVKCLENRVAVLENQNKTLIEELKALKDLYCHKSD"
     exon            296..442
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /inference="alignment:Splign:2.1.0"
     exon            443..543
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /inference="alignment:Splign:2.1.0"
     exon            544..686
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /inference="alignment:Splign:2.1.0"
     exon            687..869
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /inference="alignment:Splign:2.1.0"
     exon            870..1020
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1021..10095
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      7516..7521
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /note="hexamer: CATAAA"
     polyA_site      7538
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /note="major polyA site"
     regulatory      7957..7962
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /note="hexamer: AATAAA"
     polyA_site      7976
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
     regulatory      9640..9645
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /note="hexamer: AAGAAA"
     polyA_site      9667
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
     regulatory      9717..9722
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /note="hexamer: AATATA"
     polyA_site      9739
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
     regulatory      9926..9931
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /note="hexamer: AGTAAA"
     polyA_site      9944
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
     regulatory      10073..10078
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
                     /note="hexamer: ATTAAA"
     polyA_site      10095
                     /gene="CREB1"
                     /gene_synonym="CREB; CREB-1"
ORIGIN      
        1 agtcggcggc ggctgctgct gcctgtggcc cgggcggctg ggagaagcgg agtgttggtg
       61 agtgacgcgg cggaggtgta gtttgacgcg gtgtgttacg tgggggagag aataaaactc
      121 cagcgagatc cgggccgtga acgaaagcag tgacggagga gcttgtacca ccggtaacta
      181 aatgaccatg gaatctggag ccgagaacca gcagagtgga gatgcagctg taacagaagc
      241 tgaaaaccaa caaatgacag ttcaagccca gccacagatt gccacattag cccaggtatc
      301 tatgccagca gctcatgcaa catcatctgc tcccaccgta actctagtac agctgcccaa
      361 tgggcagaca gttcaagtcc atggagtcat tcaggcggcc cagccatcag ttattcagtc
      421 tccacaagtc caaacagttc agatttcaac tattgcagaa agtgaagatt cacaggagtc
      481 agtggatagt gtaactgatt cccaaaagcg aagggaaatt ctttcaagga ggccttccta
      541 caggaaaatt ttgaatgact tatcttctga tgcaccagga gtgccaagga ttgaagaaga
      601 gaagtctgaa gaggagactt cagcacctgc catcaccact gtaacggtgc caactccaat
      661 ttaccaaact agcagtggac agtatattgc cattacccag ggaggagcaa tacagctggc
      721 taacaatggt accgatgggg tacagggcct gcaaacatta accatgacca atgcagcagc
      781 cactcagccg ggtactacca ttctacagta tgcacagacc actgatggac agcagatctt
      841 agtgcccagc aaccaagttg ttgttcaagc tgcctctgga gacgtacaaa cataccagat
      901 tcgcacagca cccactagca ctattgcccc tggagttgtt atggcatcct ccccagcact
      961 tcctacacag cctgctgaag aagcagcacg aaagagagag gtccgtctaa tgaagaacag
     1021 ggaagcagct cgagagtgtc gtagaaagaa gaaagaatat gtgaaatgtt tagaaaacag
     1081 agtggcagtg cttgaaaatc aaaacaagac attgattgag gagctaaaag cacttaagga
     1141 cctttactgc cacaaatcag attaatttgg gatttaaatt ttcacctgtt aaggtggaaa
     1201 atggactggc ttggccacaa cctgaaagac aaaataaaca ttttattttc taaacatttc
     1261 tttttttcta tgcgcaaaac tgcctgaaag caactacaga atttcattca tttgtgcttt
     1321 tgcattaaac tgtgaatgtt ccaacacctg cctccacttc tcccctcaag aaattttcaa
     1381 cgccaggaat catgaagaga cttctgcttt tcaaccccca ccctcctcaa gaagtaataa
     1441 tttgtttact tgtaaattga tgggagaaat gaggaaaaga aaatcttttt aaaaatgatt
     1501 tcaaggtttg tgctgagctc cttgattgcc ttagggacag aattacccca gcctcttgag
     1561 ctgaagtaat gtgtgggccg catgcataaa gtaagtaagg tgcaatgaag aagtgttgat
     1621 tgccaaattg acatgttgtc acattctcat tgtgaattat gtaaagttgt taagagacat
     1681 accctctaaa aaagaacttt agcatggtat tgaaggaatt agaaatgaat ttggagtgct
     1741 ttttatgtat gttgtcttct tcaatactga aaatttgtcc ttggttctta aaagcattct
     1801 gtactaatac agctcttcca tagggcagtt gttgcttctt aattcagttc tgtatgtgtt
     1861 caacattttt gaatacatta aaagaagtaa ccaactgaac gacaaagcat ggtatttgaa
     1921 ttttaaatta aagcaaagta aataaaagta caaagcatat tttagttagt actaaattct
     1981 tagtaaaatg ctgatcagta aaccaatccc ttgagttata taacaagatt tttaaataaa
     2041 tgttattgtc ctcaccttca aaaatattta tattgtcact catttacgta aaaagatatt
     2101 tctaatttac tgttgcccat tgcacttaca taccaccacc aagaaagcct tcaagatgtc
     2161 aaataaagca aagtgatata tatttgttta tgaaatgtta catgtagaaa aatactgatt
     2221 ttaaatattt tccatattaa caatttaaca gagaatctct agtgaatttt ttaaatgaaa
     2281 gaagttgtaa ggatataaaa agtacagtgt tagatgtgca caaggaaagt tattttcaga
     2341 catatttgaa tgactgctgt actgcaatat ttggattgtc attcttacaa aacatttttt
     2401 tgttctcttg taaaaagagt agttattagt tctgctttag ctttccaata tgctgtatag
     2461 cctttgtcat tttataattt taattcctga ttaaaacagt ctgtatttgt gtatatcata
     2521 cattgttttc aataccactt ttaattgtta ctcattttat tcactaagct cgataaatct
     2581 aacagttact cttaaaaaaa aaaaaaaaag actaaggtgg attttaaaaa ttggaaactg
     2641 acataatgtt aggttataat ttctcatttg gagccgggcg cagtggctca cgcctgtaat
     2701 cccagcactt tgggaggcca aggtgggtgg atcacctgtg gtcaagagtt caagaccagc
     2761 ctggccatca tggtgaaacc ccatctctac taaaaataca aaaattagcc aggcgtggtg
     2821 gctggcgcct gtaatcccag ctactcagga ggttgaggca gcagaattgc ttgaacccag
     2881 gaggcagagg gttgcagtga gccgagatag caccattgca ctccagcctg ggcgactcca
     2941 tctcaaaaaa taaaaataaa aaaaatgtct catttgggaa ggaaattcct tttaaaaaag
     3001 agttgagaca cttagaaaac taatgtttta tatttagtca agagttattt aagaaagtca
     3061 agcttgttta acaacaaaat atgaagattt aagtgttaat tgctggatcc attttaaaat
     3121 aagattttaa ttaacatttg taaatggtat attttcgttt gtaacaaacc attgtctttt
     3181 ttcaaggatg aacagagttt atgaaggagc atcattctaa gaattaagtg atgtagtctt
     3241 tatgtttgga cagttcacca gattctcaag aaggctttca aacaactata aagtttgatg
     3301 tttgtcctgc tgagctaatg gggaaagtta tagcataaaa attgtgtaac cgcatagata
     3361 tgtcattttt aaaaactggt ttaacagaaa tcaagcaaag tcacaaatat gttcacaagt
     3421 tggaattatt tattgagtca aaatgtcgaa tcgaacattt tgaatgaagt aagtgttata
     3481 aatgaaaaat tgcctgatgt ttagcagttt gtattctcta aagctttttt tcaaaagttc
     3541 aggctttcta cttactggga agttggtggt cctcttagtc cctgataaat caaggcaatc
     3601 acattcatgt gagctggatg aatttataag ttataaagac cttatccttc ataccttgag
     3661 gatgattgca ctggttttga agtcagttgc ttaatgatga ggtgagaaat gtatcctgtt
     3721 gctaaatctg tcttagaccc ttggtgaaac ttgaagattt cagtttataa agataaaatc
     3781 aagcatcttt tgtgcagttt tcttttttta atgcaagaat ggtggggagg tttgtttgta
     3841 agcatgaaac tttgagaatc tttattaaga aaatgacata atttttaaaa accttgtagc
     3901 caagaacata tgtggccaca ttaccagtaa taaatgtttt tctctttata ttggccaaaa
     3961 gggaataaaa atgtcatcat aggaatttgt acatatgcta ctgatttgcc tagaaaatag
     4021 caagtttgat attgctcact ttgcaaatat agggccatgt ggcactttta tctataggac
     4081 agattaataa aaatgaagtg gggaggggtt tatttttgat atattactct tatgagtttt
     4141 caagctttga taatgtttaa ctgaaaagtg gcttagaaag ggctagatcc aatgtgttca
     4201 ttattaaata attgctatca gatacaattt taagttcatt ctttttcaaa ctcaagtacc
     4261 atattggcaa ccataatatt gtcataggtg ctctcttcat ttagatattc ttgggggggg
     4321 tggcatttgt ataatatatg tgtacatata tatatatata tatatatata catacagtat
     4381 ataatctaaa gctctgagag ctcttaagtc aggaatgctg agtattatag tatattgagg
     4441 tcagatgaaa ttttacattt ttgtgtgttc tgttgcattc cttctggtag tttctatgac
     4501 tgcattactc cagcactcat gattgatttt atcttctaat tttcttccaa gtattttatt
     4561 ttttattagt tttctttggc ttgatacttt taaatatgtt actagtcact tgaaagcctc
     4621 tcccccaaaa gtatttggtt tgtatgcttt gtctgtggca gctataacag tggtaagaac
     4681 attttgaaga tagcttttta aaggaaccac tgattttttc aaaaatcatc ctgggggagg
     4741 aattttggca tttcatttga gcagggattt tgtcagaaaa tgtgttttga tggtaggtca
     4801 gcagcagtgc tagtctctga aagcacaata ccagtcaggc agcctatccc atcagatgtc
     4861 atctggctga agtttatctc tgtctctcag gataaatccc tgtaggacaa atccctacta
     4921 tcatttctac cttttggggt gacatgtgga atcatacaaa ggcttaggaa gaaatacgtt
     4981 tgtttaaacc aggatgcttt acttacttga agtgacttca atctagattt cttttaatat
     5041 ttaacaaatt tttaattcta tgatcagcca cagtcagcta ttaccataaa ttggtctctg
     5101 tttattttga agatcacggc tgcttcattt tgcaggatta agtagggcta atgtatctta
     5161 aagttaagat cttgaattaa agtgagtttt agaaatagtg ttacatacct tttcagttgt
     5221 tttcaagagg ctttattttt gttgcctttg tagccctgaa agctgttggt atattttttc
     5281 cctcatggac ccaatagaaa agttgtatat ttatttggat tatatttaca ttctgtcctt
     5341 tgtaaatgtt tggtgtaact tgcacttttt taaatgaccc agtttgggta ttagcaactt
     5401 aagaaattcc ctcatcaagt aattctcaac tttttagtct ttctcctctc ttcaaatcat
     5461 gtgacttttt aaatggaagt ttttcattga ttaaaatatt ttagcaccta aaagctagcc
     5521 ttaaaaacag ctgtaaaaga aaaacatcag gaaattagat atgactagcc cagttaatta
     5581 aaagacgggc tcaaaccttg ttttattctt tttcatcttg gatgaagatt gaagggaaaa
     5641 taactcaagt gcataatatt tattttcaat ttttaatgag actttatcct catcacaaca
     5701 ttaatactgt acatagtatg ccaaaatatc cattaatttg tctagaatag tacaagactt
     5761 tttaaagcaa ttgtcctcac agagaccaca tgtaatatac tgaaatatgt tcatttttaa
     5821 tggctttgtt aacatcaaag aaatgctgcc taaatttgat ttcagatgag gaaggagaaa
     5881 gtaaagtgtg catagtaagg ctgtaggtga agagttgtga gataaatagt tcactcagtt
     5941 gtacaaagca caactagaac tttttgttgg gaggcttaca tacatcttga atattcttaa
     6001 tgtaataatg ttgactatta agttggctac acagtcactg tatgtactag gaactggttt
     6061 ccttgacatt ctagaatcaa tggctaggag aggcattaat ctttgagggg ctgaacatat
     6121 catgaagctg agtcagtatg gaaaattttc aaataaacag ggtgctgaag ttccatctgt
     6181 ctcatctgct tatgataagt tcttattgat tagtgaatgt agcttaagcc tttgtatgtg
     6241 tcctcagggg gcagaccgac tttaagaggg accagataac gtttgaatgg agggattata
     6301 tttcaggtgt tttagcttga aatttatttt ttaaaaaaag aaaaatttaa aaaatatata
     6361 aataaaatag aacaaagccg gtgatgcaag ttgatattat aaacaggcag ttttagcaca
     6421 gaaagaaaat actgacctgt ctgcattctg gtacggtggg tgcaggtccc agctgggtat
     6481 gacatgatac atttttaatt attctcacca gcaagtaaaa ggaaaatgaa caatcttttg
     6541 gaattgtctt tgaaaaggat caaagagtag gaaattcaca tttgacctaa cattacttgc
     6601 ctatagaagt atggcatttc caagcttttg tctgaggagc atctcagaga agtgagagta
     6661 aatctgagtt agcttaaaaa ttggtaggga ggaagaaaat ctctgcaaat aatgatttta
     6721 tgtttgttgg ccaagtgaaa tgatctatca ttgtgtttgg gaggttttat tttcttatgt
     6781 ttttaaaatt ggtaaatgct ttatagatgt atttttatcc aagtgccact ccaatttgtg
     6841 tatgtaataa aattatttat attaaaagtg ggaaataatt gtcaacattt tttttgagta
     6901 tagatttatt aggggtggca aagaagagtg ctagttagca gttttccatg taaagttgtc
     6961 cttgactgat ttgtccacat gtcagttgta actcccccac tccctgcaaa aggaattatt
     7021 tctaacccag atgtatcact tgaaactttt tagaagcaaa ataatcaggg aagttcctag
     7081 aaaggtgttt ggctttttgg tttttgaggg ttggggtaaa gaagacttcc cccacaactg
     7141 tcagcacaaa acagggtatt gatttttaac tctgatgttt ctattggagt tgaatactaa
     7201 ataaataact ataatgaggg aaatacattt ctaataaaat tccctacatt ctagaaacat
     7261 ccctgtttta atttttttat ctaaatcttt ttgtgcttta tgtgtaaaga aaaaaatgta
     7321 ctgagttaca atgcatttta ttaacactat gtacataata gctgctttgt gttcagaata
     7381 gtagcagttg ctttgtatat taaagtgatc cttgtgaatt tgtgaaatat tgtcataaag
     7441 tgctttttct tactgtaatc tttgtggtat caactgtcat aatgctcttt ttacacaaac
     7501 atttatgtgc agtcacataa acatgctttt aaaaactctg taagtctctt ttttggggat
     7561 gggatctcta tattttgttg ggtttttttt gctagtagtg tgaagccatg ttttattgga
     7621 cttaaagtta caatatatta caagcttgtg ttggaaggca gcaaaactaa ttcagacaac
     7681 aacatgtctt cagttactgg atccctaatt ttcaggacaa aacctgtttt tcaataagat
     7741 tgaacagtgc ctatttgtgg atttggagat gttactgtca agatgactaa tggagacata
     7801 cgaccagctg tgtctgatgt cataaaacac gtgttcactg aaaggacaat aagactatat
     7861 accttctcag gtccccttgc aattctaaaa ctctgtgatc atataaattg gaaggaaagg
     7921 ggaggggata tggttaatct ttgcttaagc tgtaagaata aaaaagttat ctcctatact
     7981 attaacttct gaaataagtt ctgagacgag acatctgaaa ataagcagct gcattatttg
     8041 tatgtttctt cactgccaag atgtgttcaa gcctgctata cctgccattg tattggaagg
     8101 cttaatgaat ttcatttatt ttctgcaaca acgattacag aatttattgc acaaaatgag
     8161 acattttgag agtgatatta attacatgag ggacaatagg catgaactag gattgttcta
     8221 agcaaatcgg aatcgggtca ccctgccacg ttcaggtgct tggaccttca ggaaaagatt
     8281 gcccatcttg tcatttgacc aggcactgaa gtgacaagac catccttgag aagtcacatc
     8341 caaagataaa attctgatcc atttctagtt ttagtgtttc gccactgaag acttaacata
     8401 tgtcttttac actcaggttg caaaacacag gcccaagaca aacttaactt ctcccccaaa
     8461 tcttccttcc gctggttttt ccatctcgta agtggtgcca ctatccatct gttaaattgt
     8521 ttaggggaaa cctagaaaag cactacctta atcagtgtta tccttcttct taactgtgcg
     8581 tcctaatttc tccacatctt tcttaagtgc agtgaccaaa ccggatgaga attctaacac
     8641 gggcctgaca tcaaatggaa aggaaggata atgtccagga gttggaatgt tatccttgtt
     8701 tttaattaag atgcaattca cataaattaa ctttttaagt gaacaattaa gtggtagtac
     8761 atccacaatg gtgtacaacc accacttcta tctagctcca aaacattctc atcactccaa
     8821 aagtaaagtc ccgttactct ccattttctc ctcccaccgc ccttgtccct ggcaaccacc
     8881 aatctgcttc ctgtttcttt ggatttacat ccgggtattt catgtgagac tcatacactg
     8941 tgtattactt ctttcgtcta gctttaatgt gttgttgagg ttgatccatt gtaacatgtt
     9001 atcactactt cattcctttt tatagctaag tatacttttt atagtaagta tgccattgta
     9061 gatatatacc acaagtttat cgattcatcc agttgagttg tttctactgt ttggctaatg
     9121 ttcatagtgc tgttatgaat gttcgtgtac aagtatttga gtccgtgttt tcaattattt
     9181 ggggtatatg cctgggagtg gagttgctgg gtcatgttga aatcgcacat ttaacttttt
     9241 gaggaactgt caaactttcc ctcagcagct gtaccgtttt accttccacc attgatgtat
     9301 gagggttcca atttctccac accttcacca acacttattt tgccatttta aaaattatag
     9361 ccatcctcat gggtgtggtc tctcattgtg gttttgattt gcatttccct gattactaat
     9421 gatgtggagc atcttttgtt gtctttggcc atctgcgtat cttctttgaa gaaatgtctg
     9481 ttgaggtcct ttgttcattg aaattttgtt gttgggttct gagttcctta tatattctgg
     9541 gtactaggcc cttataatat tttcgcctat aagtttttgc tttataatgt cctcattgtt
     9601 ttcaaactta ctttatgtaa tatgtacact tctaaaaaaa agaaacatgg aaaagggcaa
     9661 actgtaagaa gttttttgtg ttatgttttt tgtgacagtc tgtgcatata tacacaaata
     9721 taatgtatgt tctctcctcc tccctctccc tttttttaca caaaaggtag gtacaaacag
     9781 tggtttataa actgctgcca ttgtacagat acagtttaac cagtcctctt ctggggacat
     9841 ttggctgttt gaaatttttt actgttacag atatacagag gttggtaact aggtctacac
     9901 aagttgtatc tccaggatac tgagaagtaa aagttatttc tgaattatgg ttttcttcat
     9961 atttggatat tgtttcctaa tgattattag gtatctgcta agcaattttt attaacttat
    10021 gttgattact atttttatgt caaactttac agtctaggca tttttttctg gaattaaaat
    10081 tagaagtggc acaga
//
