LOCUS       NM_001369268            8960 bp    mRNA    linear   PRI 27-MAY-2024
DEFINITION  Homo sapiens aggrecan (ACAN), transcript variant 3, mRNA.
ACCESSION   NM_001369268 XM_006720419
VERSION     NM_001369268.1
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 8960)
  AUTHORS   Tang,W., Wu,K.M., Zhou,Q., Tang,Y.F., Fu,J.F., Dong,G.P. and
            Zou,C.C.
  TITLE     Genotype and phenotype in patients with ACAN gene variants: Three
            cases and literature review
  JOURNAL   Mol Genet Genomic Med 12 (4), e2439 (2024)
   PUBMED   38613222
  REMARK    GeneRIF: Genotype and phenotype in patients with ACAN gene
            variants: Three cases and literature review.
            Review article
REFERENCE   2  (bases 1 to 8960)
  AUTHORS   Wu,Y., Xia,Y., Yue,C., Xin,T., Wang,Q., Zhang,H., Shen,C., Shen,M.,
            Gu,Y. and Shen,J.
  TITLE     Brachyury positively regulates extracellular matrix synthesis via
            directly promoting aggrecan transcription in nucleus pulposus
  JOURNAL   FASEB J 37 (6), e22976 (2023)
   PUBMED   37227215
  REMARK    GeneRIF: Brachyury positively regulates extracellular matrix
            synthesis via directly promoting aggrecan transcription in nucleus
            pulposus.
REFERENCE   3  (bases 1 to 8960)
  AUTHORS   Feng,Y., Ding,S., Zhang,P., Fang,J., Li,H. and Xie,M.
  TITLE     [Analysis of a Chinese pedigree affected with familial short
            stature due to 15q25.3q26.1 deletion involving the ACAN gene]
  JOURNAL   Zhonghua Yi Xue Yi Chuan Xue Za Zhi 40 (4), 478-482 (2023)
   PUBMED   36972946
  REMARK    GeneRIF: [Analysis of a Chinese pedigree affected with familial
            short stature due to 15q25.3q26.1 deletion involving the ACAN
            gene].
REFERENCE   4  (bases 1 to 8960)
  AUTHORS   Wu,H., Wang,C., Yu,S., Ye,X., Jiang,Y., He,P. and Shan,X.
  TITLE     Downregulation of ACAN is Associated with the Growth hormone
            pathway and Induces short stature
  JOURNAL   J Clin Lab Anal 37 (2), e24830 (2023)
   PUBMED   36597844
  REMARK    GeneRIF: Downregulation of ACAN is Associated with the Growth
            hormone pathway and Induces short stature.
REFERENCE   5  (bases 1 to 8960)
  AUTHORS   Stattin,E.L., Lindblom,K., Struglics,A., Onnerfjord,P.,
            Goldblatt,J., Dixit,A., Sarkar,A., Randell,T., Suri,M., Raggio,C.,
            Davis,J., Carter,E. and Aspberg,A.
  TITLE     Novel missense ACAN gene variants linked to familial
            osteochondritis dissecans cluster in the C-terminal globular domain
            of aggrecan
  JOURNAL   Sci Rep 12 (1), 5215 (2022)
   PUBMED   35338222
  REMARK    GeneRIF: Novel missense ACAN gene variants linked to familial
            osteochondritis dissecans cluster in the C-terminal globular domain
            of aggrecan.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 8960)
  AUTHORS   Fosang,A.J., Neame,P.J., Last,K., Hardingham,T.E., Murphy,G. and
            Hamilton,J.A.
  TITLE     The interglobular domain of cartilage aggrecan is cleaved by PUMP,
            gelatinases, and cathepsin B
  JOURNAL   J Biol Chem 267 (27), 19470-19474 (1992)
   PUBMED   1326552
REFERENCE   7  (bases 1 to 8960)
  AUTHORS   Sandy,J.D., Flannery,C.R., Neame,P.J. and Lohmander,L.S.
  TITLE     The structure of aggrecan fragments in human synovial fluid.
            Evidence for the involvement in osteoarthritis of a novel
            proteinase which cleaves the Glu 373-Ala 374 bond of the
            interglobular domain
  JOURNAL   J Clin Invest 89 (5), 1512-1516 (1992)
   PUBMED   1569188
REFERENCE   8  (bases 1 to 8960)
  AUTHORS   Doege,K.J., Sasaki,M., Kimura,T. and Yamada,Y.
  TITLE     Complete coding sequence and deduced primary structure of the human
            cartilage large aggregating proteoglycan, aggrecan. Human-specific
            repeats, and additional alternatively spliced forms
  JOURNAL   J Biol Chem 266 (2), 894-902 (1991)
   PUBMED   1985970
REFERENCE   9  (bases 1 to 8960)
  AUTHORS   Baldwin,C.T., Reginato,A.M. and Prockop,D.J.
  TITLE     A new epidermal growth factor-like domain in the human core protein
            for the large cartilage-specific proteoglycan. Evidence for
            alternative splicing of the domain
  JOURNAL   J Biol Chem 264 (27), 15747-15750 (1989)
   PUBMED   2789216
REFERENCE   10 (bases 1 to 8960)
  AUTHORS   Kimata,K., Barrach,H.J., Brown,K.S. and Pennypacker,J.P.
  TITLE     Absence of proteoglycan core protein in cartilage from the cmd/cmd
            (cartilage matrix deficiency) mouse
  JOURNAL   J Biol Chem 256 (13), 6961-6968 (1981)
   PUBMED   7240256
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC103982.10.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 7, 2019 this sequence version replaced XM_006720419.1.
            
            Summary: This gene is a member of the aggrecan/versican
            proteoglycan family. The encoded protein is an integral part of the
            extracellular matrix in cartilagenous tissue and it withstands
            compression in cartilage. Mutations in this gene may be involved in
            skeletal dysplasia and spinal degeneration. Multiple alternatively
            spliced transcript variants that encode different protein isoforms
            have been observed in this gene. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (3) represents the longest
            transcript and encodes the longest isoform (3).
            
            Sequence Note: The RefSeq transcript and protein were derived from
            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##
            RNAseq introns :: mixed sample support SAMEA1966682, SAMEA1968189
                              [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            inferred exon combination :: based on alignments, homology
            MANE Ensembl match        :: ENST00000560601.4/ ENSP00000453581.2
            RefSeq Select criteria    :: based on manual assertion,
                                         conservation, longest protein
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-374               AC103982.10        114910-115283
            375-451             AC103982.10        147674-147750
            452-835             AC103982.10        150137-150520
            836-1010            AC103982.10        151486-151660
            1011-1138           AC103982.10        153214-153341
            1139-1432           AC103982.10        154829-155122
            1433-1810           AC103982.10        156979-157356
            1811-1985           AC103982.10        158717-158891
            1986-2113           AC103982.10        159385-159512
            2114-2407           AC103982.10        160912-161205
            2408-2647           AC103982.10        163268-163507
            2648-7213           AC103982.10        166326-170891
            7214-7327           AC103982.10        171800-171913
            7328-7441           AC103982.10        179690-179803
            7442-7600           AC103982.10        182856-183014
            7601-7683           AC103982.10        183477-183559
            7684-7828           AC103982.10        184355-184499
            7829-8011           AC103982.10        185316-185498
            8012-8960           AC103982.10        185879-186827
FEATURES             Location/Qualifiers
     source          1..8960
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q26.1"
     gene            1..8960
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /note="aggrecan"
                     /db_xref="GeneID:176"
                     /db_xref="HGNC:HGNC:319"
                     /db_xref="MIM:155760"
     exon            1..374
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            375..451
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     CDS             382..8088
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /note="isoform 3 precursor is encoded by transcript
                     variant 3; aggrecan core protein; cartilage-specific
                     proteoglycan core protein; large aggregating proteoglycan;
                     chondroitin sulfate proteoglycan core protein 1"
                     /codon_start=1
                     /product="aggrecan core protein isoform 3 precursor"
                     /protein_id="NP_001356197.1"
                     /db_xref="CCDS:CCDS92054.1"
                     /db_xref="GeneID:176"
                     /db_xref="HGNC:HGNC:319"
                     /db_xref="MIM:155760"
                     /translation="MTTLLWVFVTLRVITAAVTVETSDHDNSLSVSIPQPSPLRVLLG
                     TSLTIPCYFIDPMHPVTTAPSTAPLAPRIKWSRVSKEKEVVLLVATEGRVRVNSAYQD
                     KVSLPNYPAIPSDATLEVQSLRSNDSGVYRCEVMHGIEDSEATLEVVVKGIVFHYRAI
                     STRYTLDFDRAQRACLQNSAIIATPEQLQAAYEDGFHQCDAGWLADQTVRYPIHTPRE
                     GCYGDKDEFPGVRTYGIRDTNETYDVYCFAEEMEGEVFYATSPEKFTFQEAANECRRL
                     GARLATTGQLYLAWQAGMDMCSAGWLADRSVRYPISKARPNCGGNLLGVRTVYVHANQ
                     TGYPDPSSRYDAICYTGEDFVDIPENFFGVGGEEDITVQTVTWPDMELPLPRNITEGE
                     ARGSVILTVKPIFEVSPSPLEPEEPFTFAPEIGATAFAEVENETGEATRPWGFPTPGL
                     GPATAFTSEDLVVQVTAVPGQPHLPGGVVFHYRPGPTRYSLTFEEAQQACLRTGAVIA
                     SPEQLQAAYEAGYEQCDAGWLRDQTVRYPIVSPRTPCVGDKDSSPGVRTYGVRPSTET
                     YDVYCFVDRLEGEVFFATRLEQFTFQEALEFCESHNATLATTGQLYAAWSRGLDKCYA
                     GWLADGSLRYPIVTPRPACGGDKPGVRTVYLYPNQTGLPDPLSRHHAFCFRGISAVPS
                     PGEEEGGTPTSPSGVEEWIVTQVVPGVAAVPVEEETTAVPSGETTAILEFTTEPENQT
                     EWEPAYTPVGTSPLPGILPTWPPTGAATEESTEGPSATEVPSASEEPSPSEVPFPSEE
                     PSPSEEPFPSVRPFPSVELFPSEEPFPSKEPSPSEEPSASEEPYTPSPPVPSWTELPS
                     SGEESGAPDVSGDFTGSGDVSGHLDFSGQLSGDRASGLPSGDLDSSGLTSTVGSGLPV
                     ESGLPSGDEERIEWPSTPTVGELPSGAEILEGSASGVGDLSGLPSGEVLETSASGVGD
                     LSGLPSGEVLETTAPGVEDISGLPSGEVLETTAPGVEDISGLPSGEVLETTAPGVEDI
                     SGLPSGEVLETTAPGVEDISGLPSGEVLETTAPGVEDISGLPSGEVLETTAPGVEDIS
                     GLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISG
                     LPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGL
                     PSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLP
                     SGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPS
                     GEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSGEVLETAAPGVEDISGLPSG
                     EVLETAAPGVEDISGLPSGEVLETTAPGVEEISGLPSGEVLETTAPGVDEISGLPSGE
                     VLETTAPGVEEISGLPSGEVLETSTSAVGDLSGLPSGGEVLEISVSGVEDISGLPSGE
                     VVETSASGIEDVSELPSGEGLETSASGVEDLSRLPSGEEVLEISASGFGDLSGLPSGG
                     EGLETSASEVGTDLSGLPSGREGLETSASGAEDLSGLPSGKEDLVGSASGDLDLGKLP
                     SGTLGSGQAPETSGLPSGFSGEYSGVDLGSGPPSGLPDFSGLPSGFPTVSLVDSTLVE
                     VVTASTASELEGRGTIGISGAGEISGLPSSELDISGRASGLPSGTELSGQASGSPDVS
                     GEIPGLFGVSGQPSGFPDTSGETSGVTELSGLSSGQPGISGEASGVLYGTSQPFGITD
                     LSGETSGVPDLSGQPSGLPGFSGATSGVPDLVSGTTSGSGESSGITFVDTSLVEVAPT
                     TFKEEEGLGSVELSGLPSGEADLSGKSGMVDVSGQFSGTVDSSGFTSQTPEFSGLPSG
                     IAEVSGESSRAEIGSSLPSGAYYGSGTPSSFPTVSLVDRTLVESVTQAPTAQEAGEGP
                     SGILELSGAHSGAPDMSGEHSGFLDLSGLQSGLIEPSGEPPGTPYFSGDFASTTNVSG
                     ESSVAMGTSGEASGLPEVTLITSEFVEGVTEPTISQELGQRPPVTHTPQLFESSGKVS
                     TAGDISGATPVLPGSGVEVSSVPESSSETSAYPEAGFGASAAPEASREDSGSPDLSET
                     TSAFHEANLERSSGLGVSGSTLTFQEGEASAAPEVSGESTTTSDVGTEAPGLPSATPT
                     ASGDRTEISGDLSGHTSQLGVVISTSIPESEWTQQTQRPAETHLEIESSSLLYSGEET
                     HTVETATSPTDASIPASPEWKRESESTAAAPARSCAEEPCGAGTCKETEGHVICLCPP
                     GYTGEHCNIDIDECLSSPCLNGATCVDAIDSFTCLCLPSYEGDLCEIDQEVCEEGWNK
                     YQGHCYRHFPDRETWVDAERRCREQQSHLSSIVTPEEQEFVNNNAQDYQWIGLNDRTI
                     EGDFRWSDGHPMQFENWRPNQPDNFFAAGEDCVVMIWHEKGEWNDVPCNYHLPFTCKK
                     GTVACGEPPVVEHARTFGQKKDRYEINSLVRYQCTEGFVQRHMPTIRCQPSGHWEEPQ
                     ITCTDPTTYKRRLQKRSSRHPRRSRPSTAH"
     exon            452..835
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            836..1010
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            1011..1138
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            1139..1432
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            1433..1810
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            1811..1985
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            1986..2113
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            2114..2407
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            2408..2647
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            2648..7213
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            7214..7327
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            7328..7441
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            7442..7600
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            7601..7683
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            7684..7828
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            7829..8011
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     exon            8012..8960
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      8941..8946
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /note="hexamer: AATAAA"
     polyA_site      8960
                     /gene="ACAN"
                     /gene_synonym="AGC1; AGCAN; CSPG1; CSPGCP; MSK16; SEDK;
                     SSOAOD"
                     /note="major polyA site"
ORIGIN      
        1 gcccgcccac ctacctcccc gccgctccag agggggctcg cagagctgag gacgcgcgca
       61 gcgctgctca aggtctctct ctctcagcac cctcgccggc cggcgtctga cgcgggtgcc
      121 agggtctccg ggcacctttc agtgtccatt ccctcagcca gccaggactc cgcaacccag
      181 cagttgccgc tgcggccaca gcccgagggg acctgcggac aggacgccgg caggaggagg
      241 ggtgcgcagc gcccgcgcag agcgtctccc tcgctacgca gcgagacccg ggcctcccgg
      301 ccccaggagc ccccagctgc ctcgccaggt gtgtgggact gaagttcttg gagaagggag
      361 tccaactctt caaggtgaac tatgaccact ttactctggg ttttcgtgac tctgagggtc
      421 atcactgcag ctgtcactgt agaaacttca gaccatgaca actcgctgag tgtcagcatc
      481 ccccaaccgt ccccgctgag ggtcctcctg gggacctccc tcaccatccc ctgctatttc
      541 atcgacccca tgcaccctgt gaccaccgcc ccttctaccg ccccactggc cccaagaatc
      601 aagtggagcc gtgtgtccaa ggagaaggag gtagtgctgc tggtggccac tgaagggcgc
      661 gtgcgggtca acagtgccta tcaggacaag gtctcactgc ccaactaccc ggccatcccc
      721 agtgacgcca ccttggaagt ccagagcctg cgctccaatg actctggggt ctaccgctgc
      781 gaggtgatgc atggcatcga ggacagcgag gccaccctgg aagtcgtggt gaaaggcatc
      841 gtgttccatt acagagccat ctctacacgc tacaccctcg actttgacag ggcgcagcgg
      901 gcctgcctgc agaacagtgc catcattgcc acgcctgagc agctgcaggc cgcctacgaa
      961 gacggcttcc accagtgtga cgccggctgg ctggctgacc agactgtcag ataccccatc
     1021 cacactcccc gggaaggctg ctatggagac aaggatgagt ttcctggtgt gaggacgtat
     1081 ggcatccgag acaccaacga gacctatgat gtgtactgct tcgccgagga gatggagggt
     1141 gaggtctttt atgcaacatc tccagagaag ttcaccttcc aggaagcagc caatgagtgc
     1201 cggcggctgg gtgcccggct ggccaccacg ggccagctct acctggcctg gcaggctggc
     1261 atggacatgt gcagcgccgg ctggctggcc gaccgcagcg tgcgctaccc catctccaag
     1321 gcccggccca actgcggtgg caacctcctg ggcgtgagga ccgtctacgt gcatgccaac
     1381 cagacgggct accccgaccc ctcatcccgc tacgacgcca tctgctacac aggtgaagac
     1441 tttgtggaca tcccagaaaa cttctttgga gtggggggtg aggaggacat caccgtccag
     1501 acagtgacct ggcctgacat ggagctgcca ctgcctcgaa acatcactga gggtgaagcc
     1561 cgaggcagcg tgatccttac cgtaaagccc atcttcgagg tctcccccag tcccctggaa
     1621 cccgaggagc ccttcacgtt tgcccctgaa ataggggcca ctgccttcgc tgaggttgag
     1681 aatgagactg gagaggccac caggccctgg ggctttccca cacctggcct gggccctgcc
     1741 acggcattca ccagtgagga cctcgtcgtg caggtgaccg ctgtccctgg gcagccgcat
     1801 ttgccagggg gggtcgtctt ccactaccgc ccgggaccca cccgctactc gctgaccttt
     1861 gaggaggcac agcaggcctg cctgcgcacg ggggcggtca ttgcctcgcc ggagcagctc
     1921 caggccgcct acgaagcagg ctatgagcag tgtgacgccg gctggctgcg ggaccagacc
     1981 gtcagatacc ccattgtgag cccccggacc ccatgcgtgg gtgacaagga cagcagccca
     2041 ggggtcagga cctatggcgt gcgcccatca acagagacct acgatgtcta ctgctttgta
     2101 gacagacttg agggggaggt gttcttcgcc acacgccttg agcagttcac cttccaggaa
     2161 gcactggagt tctgtgaatc tcacaatgct acgctggcca ccacgggcca gctctacgcc
     2221 gcctggagcc gcggcctgga caagtgctat gccggctggc tggccgacgg cagcctccgc
     2281 taccccatcg tcaccccaag gcctgcctgc ggtggggaca agccaggcgt gagaacggtc
     2341 tacctctacc ctaaccagac gggcctccca gacccactgt cccggcacca tgccttctgc
     2401 ttccgaggca tttcagcggt tccttctcca ggagaagaag agggtggcac acccacatca
     2461 ccctctggtg tggaggagtg gatcgtgacc caagtggttc ctggtgtggc tgctgtcccc
     2521 gtagaagagg agacaactgc tgtaccctca ggggagacta ctgccatcct agagttcacc
     2581 accgagccag aaaaccagac agaatgggaa ccagcctata ccccagtggg cacatccccg
     2641 ctgccaggga tccttcctac ttggcctccc actggcgcag caacagagga aagtacagaa
     2701 ggcccttctg caactgaagt gccctctgcc tcagaggaac catccccctc agaggtgcca
     2761 ttcccctcag aggagccatc cccctcagag gaaccattcc cctcagtgag gccattcccc
     2821 tcagtggagc tgttcccctc agaggagcca ttcccctcca aggagccatc cccctcagag
     2881 gaaccatcag cctcggaaga gccgtataca ccttcacccc ccgtgcccag ctggactgag
     2941 ctgcccagct ctggggagga atctggggcc cctgatgtca gtggtgactt cacaggcagt
     3001 ggagatgttt caggacacct tgacttcagt gggcagctgt caggggacag ggcaagtgga
     3061 ctgccctctg gagacctgga ctccagtggt cttacttcca cagtgggctc aggcctgcct
     3121 gtggaaagtg gactaccctc aggggatgaa gagagaattg agtggcccag cactcctacg
     3181 gttggtgaac tgccctctgg agctgagatc ctagagggct ctgcctctgg agttggggat
     3241 ctcagtggac ttccttctgg agaagttcta gagacctctg cctctggagt aggagacctc
     3301 agtgggcttc cttctggaga agttctagag accactgccc ctggagtaga ggacatcagc
     3361 gggcttcctt ctggagaagt tctagagacc actgcccctg gagtagagga catcagcggg
     3421 cttccttctg gagaagttct agagaccact gcccctggag tagaggacat cagcgggctt
     3481 ccttctggag aagttctaga gaccactgcc cctggagtag aggacatcag cgggcttcct
     3541 tctggagaag ttctagagac cactgcccct ggagtagagg acatcagcgg gcttccttct
     3601 ggagaagttc tagagaccac tgcccctgga gtagaggaca tcagcgggct tccttctgga
     3661 gaagttctag agaccgctgc ccctggagta gaggacatca gcgggcttcc ttctggagaa
     3721 gttctagaga ccgctgcccc tggagtagag gacatcagcg ggcttccttc tggagaagtt
     3781 ctagagaccg ctgcccctgg agtagaggac atcagcgggc ttccttctgg agaagttcta
     3841 gagaccgctg cccctggagt agaggacatc agcgggcttc cttctggaga agttctagag
     3901 accgctgccc ctggagtaga ggacatcagc gggcttcctt ctggagaagt tctagagacc
     3961 gctgcccctg gagtagagga catcagcggg cttccttctg gagaagttct agagaccgct
     4021 gcccctggag tagaggacat cagcgggctt ccttctggag aagttctaga gactgctgcc
     4081 cctggagtag aggacatcag cgggcttcct tctggagaag ttctagagac tgctgcccct
     4141 ggagtagagg acatcagcgg gcttccttct ggagaagttc tagagactgc tgcccctgga
     4201 gtagaggaca tcagcgggct tccttctgga gaagttctag agactgctgc ccctggagta
     4261 gaggacatca gcgggcttcc ttctggagaa gttctagaga ctgctgcccc tggagtagag
     4321 gacatcagcg ggcttccttc tggagaagtt ctagagactg ctgcccctgg agtagaggac
     4381 atcagcgggc ttccttctgg agaagttcta gagactgctg cccctggagt agaggacatc
     4441 agcgggcttc cttctggaga agttctagag actgctgccc ctggagtaga ggacatcagc
     4501 gggcttcctt ctggagaagt tctagagact gctgcccctg gagtagagga catcagcggg
     4561 cttccttctg gagaagttct agagactact gcccctggag tagaggagat cagcgggctt
     4621 ccttctggag aagttctaga gactactgcc cctggagtag atgagatcag tgggcttcct
     4681 tctggagaag ttctagagac tactgcccct ggagtagagg agatcagcgg gcttccttct
     4741 ggagaagttc tagagacttc tacctctgcg gtaggggacc tcagtggact tccttctgga
     4801 ggagaagttc tagagatttc tgtctctgga gtagaggaca tcagtgggct tccttctgga
     4861 gaggttgtag agacttctgc ctctggaata gaggatgtca gtgaacttcc ttcaggagaa
     4921 ggtctagaga cctctgcttc tggagtagag gacctcagca ggctcccttc tggagaagaa
     4981 gttctagaga tttctgcctc tggatttggg gacctcagtg gacttccttc tggaggagaa
     5041 ggtctagaga cctctgcttc tgaagtaggg actgacctca gtgggcttcc ttctggaagg
     5101 gagggtctag agacttcagc ttctggagct gaggacctca gtgggttgcc ttctggaaaa
     5161 gaagacttgg tggggtcagc ttctggagac ttggacttgg gcaaactgcc ttctggaact
     5221 ctaggaagtg ggcaagctcc agaaacaagt ggtcttccct ctggatttag tggtgagtat
     5281 tctggggtgg accttggaag tggcccaccc tctggcctgc ctgactttag tggacttcca
     5341 tctggattcc caactgtttc cctagtggat tctacattgg tggaagtggt cacagcctcc
     5401 actgcaagtg aactggaagg gaggggaacc attggcatca gtggtgcagg agaaatatct
     5461 ggactgccct ccagtgagct ggacattagt gggagagcta gtggactccc ttcaggaact
     5521 gaactcagtg gccaagcatc tgggtctcct gatgtcagtg gggaaatacc tggactcttt
     5581 ggtgtcagtg gacagccatc agggtttcct gacactagtg gggaaacatc tggagtgact
     5641 gagcttagcg ggctgtcctc tggacaacca ggtattagtg gagaagcatc tggagttctt
     5701 tatggcacta gtcaaccctt tggcataact gatctgagtg gagaaacatc tggggtccct
     5761 gatctcagtg ggcagccttc agggttacca gggttcagtg gggcaacatc aggagtccct
     5821 gacctggttt ctggtaccac gagtggcagc ggtgaatctt ctgggattac atttgtggac
     5881 accagtttgg ttgaagtggc ccctactaca tttaaagaag aagaaggctt agggtctgtg
     5941 gaactcagtg gcctcccttc cggagaggca gatctgtcag gcaaatctgg gatggtggat
     6001 gtcagtggac agttttctgg aacagtcgat tccagtgggt ttacatccca gactccggaa
     6061 ttcagtggcc taccaagtgg catagctgag gtcagtggag aatcctccag agctgagatt
     6121 gggagcagcc tgccctcggg agcatattat ggcagtggaa ctccatctag tttccccact
     6181 gtctctcttg tagacagaac tttggtggaa tctgtaaccc aggctccaac agcccaagag
     6241 gcaggagaag ggccttctgg cattttagaa ctcagtggtg ctcattctgg agcaccagac
     6301 atgtctgggg agcattctgg atttctggac ctaagtgggc tgcagtccgg gctgatagag
     6361 cccagcggag agccaccagg tactccatat tttagtgggg attttgccag caccaccaat
     6421 gtaagtggag aatcctctgt agccatgggc accagtggag aggcctcagg acttccagaa
     6481 gttactttaa tcacttctga gttcgtggag ggtgttactg aaccaactat ttctcaggaa
     6541 ctaggccaaa ggccccctgt gacacacaca ccccagcttt ttgagtccag tggaaaagtc
     6601 tccacagctg gggacattag tggagctacc ccagtgctcc ctgggtctgg agtagaagta
     6661 tcatcagtcc cagaatctag cagtgagacg tccgcctatc ctgaagctgg gttcggggca
     6721 tctgccgccc ctgaggccag cagagaagat tctgggtccc ctgatctgag tgaaaccacc
     6781 tctgcattcc acgaagctaa ccttgagaga tcctctggcc taggagtgag cggcagcact
     6841 ttgacatttc aagaaggcga ggcgtccgct gccccagaag tgagtggaga atccaccacc
     6901 accagtgatg tggggacaga ggcaccaggc ttgccttcag ccactcccac ggcttctgga
     6961 gacaggactg aaatcagcgg agacctgtct ggtcacacct cgcagctggg cgttgtcatc
     7021 agcaccagca tcccagagtc tgagtggacc cagcagaccc agcgccctgc agagacgcat
     7081 ctagaaattg agtcctcaag cctcctgtac tcaggagaag agactcacac agtcgaaaca
     7141 gccacctccc caacagatgc ttccatccca gcttctccgg aatggaaacg tgaatcagaa
     7201 tcaactgctg cagcccccgc caggtcctgt gcagaggagc cctgtggagc tgggacctgc
     7261 aaggagacag agggacacgt catatgcctg tgcccccctg gctacactgg cgagcactgt
     7321 aacatagaca ttgatgagtg cctctcaagc ccttgtctga atggagccac ctgcgtggat
     7381 gccatcgact ctttcacatg cttatgcctt cccagctacg aaggggacct gtgtgagatt
     7441 gaccaggagg tatgtgagga gggctggaac aagtaccagg gccactgtta ccgccacttc
     7501 ccggaccgcg agacctgggt ggatgctgag cgccggtgtc gggagcagca gtcacacctg
     7561 agcagcatcg tcacccccga ggagcaggag tttgtcaaca acaatgccca agactaccag
     7621 tggatcggcc tgaacgacag gaccatcgaa ggggacttcc gctggtcaga tggacacccc
     7681 atgcaatttg agaactggcg ccccaaccag cctgacaact tttttgccgc tggagaggac
     7741 tgtgtggtga tgatctggca cgagaagggc gagtggaatg atgttccctg caattaccac
     7801 ctccccttca cgtgtaaaaa gggcacagtg gcctgcggag agccccctgt ggtggagcat
     7861 gccaggacct tcgggcagaa gaaggaccgg tatgagatca attccctggt gcggtaccag
     7921 tgcacagagg ggtttgtcca gcgccacatg cccaccatcc ggtgccagcc cagcgggcac
     7981 tgggaggagc ctcagatcac ctgcacagac cccaccacct acaaacgcag actacagaag
     8041 cggagctcac ggcaccctcg gaggagccgc cccagcacag cccactgaga agagcttcca
     8101 ggacgcaccc aggacgctga gcccaggagc ctgccaggct gacgtgcatc ccacccagac
     8161 ggtgtcctct tcttgtcgct ttttgtcata taaggaatcc cattaaagaa ggaaaaaaat
     8221 aaatcccaca tttgtgtatg cacccactca cccctccaaa tcagcaaaac cgcatctaat
     8281 ttgtccgccg aatgccaaag caaagcaaac ttattataac ccttggactg agtttagaga
     8341 catttcttca atttcccatc gtgcctttcc agggaccagt gcagggacag ggggagaagg
     8401 ggaggggtta agttaaataa agaagattat ttttgtttcc tgactttatc caagagcagt
     8461 gcaatcgttg gttatttcac ctccagggag agctagggag gagggaggag ggctccaaag
     8521 gagctggaag gagcagaggc ctgagagcag gaagaactcg gaaccgcagc tgaatgtatt
     8581 ggatgagaag gagccaggag ggctacacca tctgtatgag ggaaaagcct tgggggagag
     8641 gggtgggttc ctgcctcctg ccgagggtaa gccggcagga gagagccatc agagggacct
     8701 ccgctgcctg ggagttgggt tccctccaag ggtccctctt tcagtgtcct ctctctcacc
     8761 tgggtctgcc accctaacag gtggcaactc ggcagggctg ctgggggcac ttcctgccca
     8821 gtggggggtg ccgcccaacc ttctcccctc cccacccccg cccccgggac cgtgcaggca
     8881 ccagggttcc gtgcacctat ttatattttt gaaaactgaa gattataata ttataataat
     8941 aataaagaca ttggaagaga
//
