LOCUS       NM_018448              11176 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens cullin associated and neddylation dissociated 1
            (CAND1), transcript variant 1, mRNA.
ACCESSION   NM_018448
VERSION     NM_018448.5
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 11176)
  AUTHORS   Ao,Y.Q., Gao,J., Jin,C., Wang,S., Zhang,L.C., Deng,J., Chen,Z.W.,
            Wang,H.K., Jiang,J.H. and Ding,J.Y.
  TITLE     ASCC3 promotes the immunosuppression and progression of non-small
            cell lung cancer by impairing the type I interferon response via
            CAND1-mediated ubiquitination inhibition of STAT3
  JOURNAL   J Immunother Cancer 11 (12), e007766 (2023)
   PUBMED   38148115
  REMARK    GeneRIF: ASCC3 promotes the immunosuppression and progression of
            non-small cell lung cancer by impairing the type I interferon
            response via CAND1-mediated ubiquitination inhibition of STAT3.
            Erratum:[J Immunother Cancer. 2024 Jul 10;12(7):e007766corr1. doi:
            10.1136/jitc-2023-007766corr1.. PMID: 38986545]
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 11176)
  AUTHORS   Shaaban,M., Clapperton,J.A., Ding,S., Kunzelmann,S., Maeots,M.E.,
            Maslen,S.L., Skehel,J.M. and Enchev,R.I.
  TITLE     Structural and mechanistic insights into the CAND1-mediated SCF
            substrate receptor exchange
  JOURNAL   Mol Cell 83 (13), 2332-2346 (2023)
   PUBMED   37339624
  REMARK    GeneRIF: Structural and mechanistic insights into the
            CAND1-mediated SCF substrate receptor exchange.
REFERENCE   3  (bases 1 to 11176)
  AUTHORS   Pierce,N.W., Lee,J.E., Liu,X., Sweredoski,M.J., Graham,R.L.,
            Larimore,E.A., Rome,M., Zheng,N., Clurman,B.E., Hess,S., Shan,S.O.
            and Deshaies,R.J.
  TITLE     Cand1 promotes assembly of new SCF complexes through dynamic
            exchange of F box proteins
  JOURNAL   Cell 153 (1), 206-215 (2013)
   PUBMED   23453757
  REMARK    GeneRIF: Study shows that Cand1 can unambiguously stimulate SCF
            activity in vitro by enabling an F box protein-Skp1 complex to
            access Cul1 that was previously occupied by a different F box
            protein-Skp1 complex, and that Cand1 promotes assembly in vivo of
            new F box proteins with pre-existing Cul1 molecules.
REFERENCE   4  (bases 1 to 11176)
  AUTHORS   Mao,X., Gluck,N., Chen,B., Starokadomskyy,P., Li,H., Maine,G.N. and
            Burstein,E.
  TITLE     COMMD1 (copper metabolism MURR1 domain-containing protein 1)
            regulates Cullin RING ligases by preventing CAND1
            (Cullin-associated Nedd8-dissociated protein 1) binding
  JOURNAL   J Biol Chem 286 (37), 32355-32365 (2011)
   PUBMED   21778237
  REMARK    GeneRIF: COMMD1 (copper metabolism MURR1 domain-containing protein
            1) regulates Cullin RING ligases by preventing CAND1
            (Cullin-associated Nedd8-dissociated protein 1) binding.
REFERENCE   5  (bases 1 to 11176)
  AUTHORS   Chua,Y.S., Boh,B.K., Ponyeam,W. and Hagen,T.
  TITLE     Regulation of cullin RING E3 ubiquitin ligases by CAND1 in vivo
  JOURNAL   PLoS One 6 (1), e16071 (2011)
   PUBMED   21249194
  REMARK    GeneRIF: CAND1 does not function by sequestering cullins in vivo to
            prevent substrate receptor autoubiquitination and is likely to
            regulate cullin RING ligase activity via alternative mechanisms
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 11176)
  AUTHORS   Goldenberg,S.J., Cascio,T.C., Shumway,S.D., Garbutt,K.C., Liu,J.,
            Xiong,Y. and Zheng,N.
  TITLE     Structure of the Cand1-Cul1-Roc1 complex reveals regulatory
            mechanisms for the assembly of the multisubunit cullin-dependent
            ubiquitin ligases
  JOURNAL   Cell 119 (4), 517-528 (2004)
   PUBMED   15537541
REFERENCE   7  (bases 1 to 11176)
  AUTHORS   Zheng,J., Yang,X., Harrell,J.M., Ryzhikov,S., Shim,E.H.,
            Lykke-Andersen,K., Wei,N., Sun,H., Kobayashi,R. and Zhang,H.
  TITLE     CAND1 binds to unneddylated CUL1 and regulates the formation of SCF
            ubiquitin E3 ligase complex
  JOURNAL   Mol Cell 10 (6), 1519-1526 (2002)
   PUBMED   12504026
  REMARK    GeneRIF: binds to unneddylated CUL1 and regulates the formation of
            SCF ubiquitin E3 ligase complex
REFERENCE   8  (bases 1 to 11176)
  AUTHORS   Liu,J., Furukawa,M., Matsumoto,T. and Xiong,Y.
  TITLE     NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of
            CUL1-SKP1 binding and SCF ligases
  JOURNAL   Mol Cell 10 (6), 1511-1518 (2002)
   PUBMED   12504025
  REMARK    GeneRIF: selectively binds to unneddylated CUL1 and is dissociated
            by CUL1 neddylation
REFERENCE   9  (bases 1 to 11176)
  AUTHORS   Yogosawa,S., Kayukawa,K., Kawata,T., Makino,Y., Inoue,S., Okuda,A.,
            Muramatsu,M. and Tamura,T.
  TITLE     Induced expression, localization, and chromosome mapping of a gene
            for the TBP-interacting protein 120A
  JOURNAL   Biochem Biophys Res Commun 266 (1), 123-128 (1999)
   PUBMED   10581176
REFERENCE   10 (bases 1 to 11176)
  AUTHORS   Yogosawa,S., Makino,Y., Yoshida,T., Kishimoto,T., Muramatsu,M. and
            Tamura,T.
  TITLE     Molecular cloning of a novel 120-kDa TBP-interacting protein
  JOURNAL   Biochem Biophys Res Commun 229 (2), 612-617 (1996)
   PUBMED   8954946
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB064887.1, AL136810.1,
            AB020636.2, BQ024785.1 and AC078983.17.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_018448.4.
            
            Summary: This gene encodes an essential regulator of Cullin-RING
            ubiquitin ligases, which are in involved in ubiquitinylation of
            proteins degraded by the Ub proteasome system. The encoded protein
            binds to unneddylated cullin-RING box protein complexes and acts as
            an inhibitor of cullin neddylation and of Skp1, cullin, and F box
            ubiquitin ligase complex assembly and activity. In mammalian cell
            culture, this protein predominantly localizes to the cytoplasm.
            Knockdown of this gene in preadipocytes results in blocked
            adipogenesis. Alternative splicing results in multiple transcript
            variants. [provided by RefSeq, Jul 2016].
            
            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 :: SRR1803612.200182.1,
                                           SRR1803616.9626.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000545606.6/ ENSP00000442318.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-11                DB064887.1         79-89
            12-5365             AL136810.1         1-5354
            5366-5834           AB020636.2         5345-5813
            5835-5915           BQ024785.1         19-99               c
            5916-11176          AC078983.17        138644-143904       c
FEATURES             Location/Qualifiers
     source          1..11176
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q14.3-q15"
     gene            1..11176
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /note="cullin associated and neddylation dissociated 1"
                     /db_xref="GeneID:55832"
                     /db_xref="HGNC:HGNC:30688"
                     /db_xref="MIM:607727"
     exon            1..428
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     CDS             361..4053
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /note="isoform 1 is encoded by transcript variant 1;
                     cullin-associated NEDD8-dissociated protein 1; p120 CAND1;
                     TBP-interacting protein of 120 kDa A"
                     /codon_start=1
                     /product="cullin-associated NEDD8-dissociated protein 1
                     isoform 1"
                     /protein_id="NP_060918.2"
                     /db_xref="CCDS:CCDS8977.1"
                     /db_xref="GeneID:55832"
                     /db_xref="HGNC:HGNC:30688"
                     /db_xref="MIM:607727"
                     /translation="MASASYHISNLLEKMTSSDKDFRFMATNDLMTELQKDSIKLDDD
                     SERKVVKMILKLLEDKNGEVQNLAVKCLGPLVSKVKEYQVETIVDTLCTNMLSDKEQL
                     RDISSIGLKTVIGELPPASSGSALAANVCKKITGRLTSAIAKQEDVSVQLEALDIMAD
                     MLSRQGGLLVNFHPSILTCLLPQLTSPRLAVRKRTIIALGHLVMSCGNIVFVDLIEHL
                     LSELSKNDSMSTTRTYIQCIAAISRQAGHRIGEYLEKIIPLVVKFCNVDDDELREYCI
                     QAFESFVRRCPKEVYPHVSTIINICLKYLTYDPNYNYDDEDEDENAMDADGGDDDDQG
                     SDDEYSDDDDMSWKVRRAAAKCLDAVVSTRHEMLPEFYKTVSPALISRFKEREENVKA
                     DVFHAYLSLLKQTRPVQSWLCDPDAMEQGETPLTMLQSQVPNIVKALHKQMKEKSVKT
                     RQCCFNMLTELVNVLPGALTQHIPVLVPGIIFSLNDKSSSSNLKIDALSCLYVILCNH
                     SPQVFHPHVQALVPPVVACVGDPFYKITSEALLVTQQLVKVIRPLDQPSSFDATPYIK
                     DLFTCTIKRLKAADIDQEVKERAISCMGQIICNLGDNLGSDLPNTLQIFLERLKNEIT
                     RLTTVKALTLIAGSPLKIDLRPVLGEGVPILASFLRKNQRALKLGTLSALDILIKNYS
                     DSLTAAMIDAVLDELPPLISESDMHVSQMAISFLTTLAKVYPSSLSKISGSILNELIG
                     LVRSPLLQGGALSAMLDFFQALVVTGTNNLGYMDLLRMLTGPVYSQSTALTHKQSYYS
                     IAKCVAALTRACPKEGPAVVGQFIQDVKNSRSTDSIRLLALLSLGEVGHHIDLSGQLE
                     LKSVILEAFSSPSEEVKSAASYALGSISVGNLPEYLPFVLQEITSQPKRQYLLLHSLK
                     EIISSASVVGLKPYVENIWALLLKHCECAEEGTRNVVAECLGKLTLIDPETLLPRLKG
                     YLISGSSYARSSVVTAVKFTISDHPQPIDPLLKNCIGDFLKTLEDPDLNVRRVALVTF
                     NSAAHNKPSLIRDLLDTVLPHLYNETKVRKELIREVEMGPFKHTVDDGLDIRKAAFEC
                     MYTLLDSCLDRLDIFEFLNHVEDGLKDHYDIKMLTFLMLVRLSTLCPSAVLQRLDRLV
                     EPLRATCTTKVKANSVKQEFEKQDELKRSAMRAVAALLTIPEAEKSPLMSEFQSQISS
                     NPELAAIFESIQKDSSSTNLESMDTS"
     exon            429..572
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            573..727
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            728..851
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            852..1108
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            1109..1214
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            1215..1360
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            1361..1653
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            1654..1795
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            1796..3289
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            3290..3385
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            3386..3555
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            3556..3720
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            3721..3828
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     exon            3829..11176
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4376..4381
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /note="hexamer: ATTAAA"
     polyA_site      4405
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /note="major polyA site"
     regulatory      4417..4422
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /note="hexamer: TATAAA"
     polyA_site      4461
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
     regulatory      5815..5820
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /note="hexamer: ATTACA"
     polyA_site      5843
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /note="major polyA site"
     regulatory      7481..7486
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /note="hexamer: AATAAA"
     polyA_site      7513
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
     regulatory      11156..11161
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
                     /note="hexamer: AATAAA"
     polyA_site      11176
                     /gene="CAND1"
                     /gene_synonym="TIP120; TIP120A"
ORIGIN      
        1 cttttgccct agggagcgag tgcggagcga gtgggagcga gacggccctg agtggaagtg
       61 tctggctccc cgtagaggcc cttctgtacg ccccgccgcc catgagctcg ttctcacgcg
      121 aacagcgccg tcgttaggct ggctctgtag cctcggctta ccccgggaca ggcccacgcc
      181 tcgccaggga gggggcagcc cgtcgaggcg cctccctagt cagcgtcggc gtcgcgctgc
      241 gaccctggaa gcgggagccg ccgcgagcga gaggaggagc tccagtggcg gcggcggcgg
      301 cggcagcggc agcgggcagc agctccagca gcgccagcag gcgggatcga ggccgtcaac
      361 atggcgagcg cctcgtacca catttccaat ttgctggaaa aaatgacatc cagcgacaag
      421 gactttaggt ttatggctac aaatgatttg atgacggaac tgcagaaaga ttccatcaag
      481 ttggatgatg atagtgaaag gaaagtagtg aaaatgattt tgaagttatt ggaagataaa
      541 aatggagagg tacagaattt agctgtcaaa tgtcttggtc ctttagtgag taaagtgaaa
      601 gaataccaag tagagacaat tgtagatacc ctctgcacta acatgctttc tgataaagaa
      661 caacttcgag acatttcaag tattggtctt aaaacagtaa ttggagaact tcctccagct
      721 tccagtggct ctgcattagc tgctaatgta tgtaaaaaga ttactggacg tcttacaagt
      781 gcaatagcaa aacaggaaga tgtctctgtt cagctagaag ccttggatat tatggctgat
      841 atgttgagca ggcaaggagg acttcttgtt aatttccatc cttcaattct gacctgtcta
      901 cttccccagt tgaccagccc tagacttgca gtgaggaaaa gaaccattat cgctcttggc
      961 catctggtta tgagctgtgg aaatatagtt tttgtagatc ttattgaaca tctgttgtca
     1021 gagttgtcca aaaatgattc tatgtcaaca acaagaacct acatacaatg tattgctgct
     1081 attagtaggc aagctggtca tagaataggt gaataccttg agaagataat tcctttggtg
     1141 gtaaaatttt gcaatgtaga tgatgatgaa ttaagagagt actgtattca agcctttgaa
     1201 tcatttgtaa gaagatgtcc taaggaagta tatcctcatg tttctaccat tataaatatt
     1261 tgtcttaaat atcttaccta tgatccaaat tataattacg atgatgaaga tgaagatgaa
     1321 aatgcaatgg atgctgatgg tggtgatgat gatgatcaag ggagtgatga tgaatacagt
     1381 gatgatgatg acatgagttg gaaagtgaga cgtgcagctg cgaagtgctt ggatgctgta
     1441 gttagcacaa ggcatgaaat gcttccagaa ttctacaaga ccgtctctcc tgcactaata
     1501 tccagattta aagagcgtga agagaatgta aaggcagatg tttttcacgc atacctttct
     1561 cttttgaagc aaactcgtcc tgtacaaagt tggctatgtg accctgatgc aatggagcag
     1621 ggagaaacac ctttaacaat gcttcagagt caggttccca acattgttaa agctcttcac
     1681 aaacagatga aagaaaaaag tgtgaagacc cgacagtgtt gttttaacat gttaactgag
     1741 ctggtaaatg tattacctgg ggccctaact caacacattc ctgtacttgt accaggaatc
     1801 attttctcac tgaatgataa atcaagctca tcgaatttga agatcgatgc tttgtcatgt
     1861 ctatacgtaa tcctctgtaa ccattctcct caagtcttcc atcctcacgt tcaggctttg
     1921 gttcctccag tggtggcttg tgttggagac ccattttaca aaattacatc tgaagcactt
     1981 cttgttactc aacagcttgt caaagtaatt cgtcctttag atcagccttc ctcgtttgat
     2041 gcaactcctt atatcaaaga tctatttacc tgtaccatta agagattaaa agcagctgac
     2101 attgatcagg aagtcaagga aagggctatt tcctgtatgg gacaaattat ttgcaacctt
     2161 ggagacaatt tgggttctga cttgcctaat acacttcaga ttttcttgga gagactaaag
     2221 aatgaaatta ccaggttaac tacagtaaag gcattgacac tgattgctgg gtcacctttg
     2281 aagatagatt tgaggcctgt tctgggagaa ggggttccta tccttgcttc atttcttaga
     2341 aaaaaccaga gagctttgaa actgggtact ctttctgccc ttgatattct aataaaaaac
     2401 tatagtgaca gcttgacagc tgccatgatt gatgcagttc tagatgagct cccacctctt
     2461 atcagcgaaa gtgatatgca tgtttcacaa atggccatca gttttcttac cactttggca
     2521 aaagtatatc cctcctccct ttcaaagata agtggatcca ttctcaatga acttattgga
     2581 cttgtgagat cacccttatt gcagggggga gctcttagtg ccatgctaga ctttttccaa
     2641 gctctggttg tcactggaac aaataattta ggatacatgg atttgttgcg catgctgact
     2701 ggtccagttt actctcagag cacagctctt actcataagc agtcttatta ttccattgcc
     2761 aaatgtgtag ctgcccttac tcgagcatgc cctaaagagg gaccagctgt agtaggtcag
     2821 tttattcaag atgtcaagaa ctcaaggtct acagattcca ttcgtctctt agctctactt
     2881 tctcttggag aagttgggca tcatattgac ttaagtggac agttggaact aaaatctgta
     2941 atactagaag ctttctcatc tcctagtgaa gaagtcaaat cagctgcatc ctatgcatta
     3001 ggcagcatta gtgtgggcaa ccttcctgaa tatctgccgt ttgtcctgca agaaataact
     3061 agtcaaccca aaaggcagta tcttttactt cattccttga aggaaattat tagctctgca
     3121 tcagtggtgg gccttaaacc atatgttgaa aacatctggg ccttattact aaagcactgt
     3181 gagtgtgcag aggaaggaac cagaaatgtt gttgctgaat gtctaggaaa actcactcta
     3241 attgatccag aaactctcct tccacggctt aaggggtact tgatatcagg ctcatcatat
     3301 gcccgaagct cagtggttac ggctgtgaaa tttacaattt ctgaccatcc acaacctatt
     3361 gatccactgt taaagaactg cataggtgat ttcctaaaaa ctttggaaga cccagatttg
     3421 aatgtgagaa gagtagcctt ggtcacattt aattcagcag cacataacaa gccatcatta
     3481 ataagggatc tattggatac tgttcttcca catctttaca atgaaacaaa agttagaaag
     3541 gagcttataa gagaggtaga aatgggtcca tttaaacata cggttgatga tggtctggat
     3601 attagaaagg cagcatttga gtgtatgtac acacttctag acagttgtct tgatagactt
     3661 gatatctttg aatttctaaa tcatgttgaa gatggtttga aggaccatta tgatattaag
     3721 atgctgacat ttttaatgtt ggtgagactg tctacccttt gtccaagtgc agtactgcag
     3781 aggttggacc gacttgttga gccattacgt gcaacatgta caactaaggt aaaggcaaac
     3841 tcagtaaagc aggagtttga aaaacaagat gaattaaagc gatctgccat gagagcagta
     3901 gcagcactgc taaccattcc agaagcagag aagagtccac tgatgagtga attccagtca
     3961 cagatcagtt ctaaccctga gctggcggct atctttgaaa gtatccagaa agattcatca
     4021 tctactaact tggaatcaat ggacactagt tagatgtttg ttcaccatgg ggaccattac
     4081 atatgaccat acaatgcact gaattgacag gttaatcata agacatggaa agagaagtgt
     4141 ctaaaagctt caaaatgttc cacttttttt tccttcatgg agactgtttg tttggctttc
     4201 ttccattgtt gtttttgtag catttatttc agaaatgtgt atttccataa tccagaggtt
     4261 gtaaaaccac tagtgtttta gtggttacag caacatttga aatggaaact aaaagttagg
     4321 attttatgga gtatggagat agggtccagt atctatttac cctgtaatgt ttaggattaa
     4381 aatgttaaaa ttttgtgacc atgaatttct ttcttttata aattttctca tttaaaaatc
     4441 aaaaatcttg caaaacaaaa accatgtttc tttttcttgt ataacttttt gttttcagca
     4501 acataaattg atttttagct ggcagacaag aatatccata taagatttgt taaccatttc
     4561 agagagtttg gcaattttta aaagataata aggtatcatt tttaagtatg aaaattaaca
     4621 atatccctgt tgcgcacact aattttgcat gagtaagttt acaaatatgt atcgtctgta
     4681 aagcagcatg tgcagattat tcataatata gaagttaaaa taagtattag tgcaattttc
     4741 agatatttat ttttgcacag aaaacacatt atctggagag aaagaaagga gaatttttga
     4801 gacttgggtt ttcttaatgc cagtgtgaat ttgcagatgt tttcagaaaa tcaagtcaca
     4861 gtaacaattt gccacttttt tctattataa atcttcttac ttaaattttg aatatttagt
     4921 ttttctcagt tacccatttg tgtgtgtgtg attccactta gaaattctta aaaccagatt
     4981 tttctttcat tccgtttgga tgtctacatt ccttatcaaa ggatataaat actgtgtatg
     5041 cttttgaatt ttatttttag gaaaattctg aagccagcta tcacaggttt gttagctaat
     5101 aatagtattt tcttttagtt gagttaggtt tttccccatc tcctgtagag cgaatttaca
     5161 tattgtattg ggtaagtgtt cactactttt cctgattaag ggatctgtgc tggggaacaa
     5221 agcttttgca gtaccttata ttgtagttaa aattttattt aacatatcct tcagtgagct
     5281 catttcacac tgtagcctct tccttaaaat ttgtggtgct cctgtaacag taagaactaa
     5341 ttctgaaata aaagacatct cctaatgctg tgcaaacata gtttacatgt attgaaggag
     5401 gcagttgtta aattgagtga ccaatttaag caatcagata tttgaaaact gcacccttta
     5461 gttttgaaac tgtgaattag aaacactttt cctgctgtat tactacctgc tttaacatcc
     5521 aaatatacag tgattttaaa tgataacata ctgtggttat tagattaaca gcttgatttt
     5581 gaatgttcag atgataatgc agaagacatc acttctagta aggattttga ctagtgcatt
     5641 gatgttgaag ttggtgccat ttcaaaatgt ggcaggtgat aatcttttac cataatttgc
     5701 ataaaactgt aatagaagtt tattttgaga tgttagtata ttatgtacta tgcatttctg
     5761 tggtatagat gttgtggata tatttaagta tttggttaca tggttttaca ataaattaca
     5821 atactgcagg ctctaggact gaacaggaga ctgacatgca tatgttgtgt gaatgtctta
     5881 gttgggtaaa gttaaatcca aatacttcaa ctggcttttt cttcagtttg tttgttttta
     5941 actttcaaga tgcatgtttt gttttgtttt gctttgtttt tgtctcttaa gccaattcat
     6001 ttttctaaca gttgaaattc ttttagtact aaagaaatag atactgctct tttatggctt
     6061 tagtgtttat atacctgttt atatgcatac attaacaaaa ttagtaacag cagtgcttag
     6121 aatttcaatg ctgtgtcata ctgatgatta actccatact cctagtggtg atgtggtcca
     6181 gatactggaa tggaagtggc aggatgtgga gtccagacat agtctaccac tcatgctact
     6241 tactagtaat attaaggtgt taaacttagg aatttgtcac atgtaggttc ctgaggagat
     6301 ctaaaagtta atacaaaacc aagctgttta ctgattttca tgagaacatt taagttagtt
     6361 taggtctacc tgatttattt taaaagaagg cagagggctg gacgcagtgg cttacgcctg
     6421 taatcccagc actttgggag gccgaggcgg gcggatcacg aggtcaggag atcgagacta
     6481 tcctggctaa cactgtgaaa acccatctct actgaaaata caaaaaatta gctgggcgtg
     6541 gtggcagacg cctgtagtcc tagctgctac agctgaggca ggagaatggc gtgaacccag
     6601 gaggcggagc tggcagtgag ccgagatcac gccactgcac tctggcctgg gcaacagagc
     6661 gagagtctgt ctcaaaaaaa aaaaaaaaaa aaaggcagga aggaaatttg gtatggcagg
     6721 gcctaaccta aaaggttatt tataaaatca atagcactga atgataattt ttttaatgac
     6781 agtcatgtat tttattaatg atatctgaaa gctgcttaac cattaggaat tacaattctt
     6841 tatggttgga gtatgatgat ttcatcaaat gtttgaatat ttacataatt tttatgtaac
     6901 cataattaaa ccaaattagt ctttttttct tcatactttt cttcggtaaa tagtgaagaa
     6961 ataatgggca tatctaatta accagttcta gtgggtgttg tgatatcttt atatctagtt
     7021 cagtctcaga tgtatgaata tgattatata gtcatgattg aagttcaaaa tgaggaagta
     7081 tacaaaatcc tcagccactg aaaaattcag ttaacttgtt tatactcctg taagctctag
     7141 ttagtcacaa gacaaagtat atagtaacac tttgtaatga agtaacattt tctgcccaca
     7201 ttaattttac taaagaccta aattgttaaa attaattgcc aatctctgga tatattatgc
     7261 ttagtaagtg ttttgaaatt aaagacctta aacatttcag caagtaaatt ttggattcta
     7321 gctctgtttt aaattgaatc ctaattttca aaccactgct accccagatt catacctgtt
     7381 tttgaaatct tgtttatgga atggaaaatt gacagtatgg taatagttta ttgactgatt
     7441 ggacaaagga tattctggtt ttaactgact tttccattta aataaaattc atttgataat
     7501 tttggttgca aaagtggaac acagtggaag tatttggcta caggctaccc aaatctcatc
     7561 agataaggct gttttcttaa aggaaatgca aaatgaaatc atatgttttc cttttccaat
     7621 acagtaaatt gcttgttttc ctatgaatat cagaaaagat tttgtaaaca cctttgctgt
     7681 agtttcaggc aagatctttc agcaacatgt ttttgctctt tgtaacttag aaagttagct
     7741 ctgaatccaa aaactactga agtgagtaat gcatataatt ttactttttt ggaccctata
     7801 atgccagtgt gtcaggtttc agaatgatat ttagtagaca gaaataccta attttgtttt
     7861 ggaatcttaa taccctgtcc tcttcataac tttctagtgg tgattttagc aagtttaatt
     7921 attttgctga ggtcttagaa gacagaaagc ttatgctatg taaagtgaca ttgtttccag
     7981 attaggaagt attggaatta atttgctatt gccagtaagt aatggttgat ggatattaag
     8041 tgattttagt ctagaatgct ctcaaaaaaa tagtaaagaa ttgtacttca gggccagatg
     8101 gcagctcacg cctgtaatct cagcactttg ggaggccaag gtgggggatc acttgaagac
     8161 aggagttgga gaccagctct aggcaacata gtgagaccct gtctctacca aaaagaagaa
     8221 aaaagaaatc aacaacatgc aaccataaga atggatgaga tggccctaaa agaataagga
     8281 ttacatataa tgagaagacg tgtgggctga aatacctagt gaacaatatt taagggaaac
     8341 tgaagtgcaa atggcctcac aggtttgttt ttgtgtttaa gacaaggtct cactctgttg
     8401 cctggactgg agtacatagc acgaacatgg tttactgcac ctcagcttcc tgggcacaag
     8461 tgattctccc acctcagcct cccgagtagc tgggagtata ggtgtgtgcc accacgtcca
     8521 gctaattttt ttatttcctt gtggagatgg ggtctcatga ccttgtccag gatgatctca
     8581 aactcctggg ctcaagcaat cctgtgttgg cctcctaaac tgctgagatt attgcaagtg
     8641 cctccttgcc cagccacatg ttgttgattt cttttttctt tttttttctt tcttaatttt
     8701 tttttttttt tttttttttg agattgatgg agtcttgctt tgtctcccag gctggagtgc
     8761 agtggcgcaa tatcggctca ctgcaacctc tgcctcccgg gttctagcta ttctcctgcc
     8821 tcagcctccc aagtagctgt gattacaggc gtgtgccacc atgcccagct aatttttgta
     8881 tttttagtag agatggagtt ttgccatgtt ggccaggctg gtttcaaact cctgatctta
     8941 ggtgatacac ccgcctcggc ctcccaaagt gctgggatta caggcgtgag ccacgtcccc
     9001 cagccagttt cttaatctat acatctagcc cagtccatgc ccctgtttca gactattata
     9061 tccaaccacc tgctatacat ctcataaagg tatctcaaac acagcatatc taaagctgaa
     9121 gtcatcatct tgccctggtt tttcctgtct ctttgctgat ggcatcccat ttacccagtc
     9181 attcaaactg gaaatctaaa agcctcactt agcaagagtt tggaggcaga atatgataaa
     9241 gaacaaggac tctgggaggc caaggcaggt ggattgcttg aggtcaagag ttcgagacca
     9301 gtctggccaa catggcgaaa ccccgtcttt gctaaaaaaa cacaaagaaa ttagctagac
     9361 gtggtggcac atgcctgtag tcccagctgt gtgggaggct gaggcagggg aattgcttga
     9421 acctgggagg tggaggttgc agtgacccaa gattgcatgc accactgcac tccagcctgg
     9481 gtgacaaagc gagaccctgt ctcaaaaaaa acaaggactc tacagataga tagacatcat
     9541 atatcatatt agtttgaatc ctggctgtta gctgttagac ttgggcaaat aatttaacct
     9601 caactttccc tatctataaa atgggaatta aaatatttgc accttatagg gttattgtga
     9661 ggattaaata ggaacattgt ataaagcact taaaacagta cctgggacat actaagtaat
     9721 ataattgtta actcttacta gcattctgtc ccttttattt cctaaatatc tctcatgccc
     9781 atctcctaaa tatctctttc ctaaatatct ctcatgcttt tggcttaaga cctcttttcc
     9841 tccttatcta ttgactggac tgcggcaaat gcctgctaat cgttattttt gtgttcattc
     9901 atttagcaag ccaatttatt acgcgcttag ggtgctgcca gggctacaaa agctgttgag
     9961 actgtacttg atatgaagaa gcttgctgat tatcatggga agactgacat aaggaagcac
    10021 cataaaattc tgctgtatga gaggtataca cgggatactg ggggttaata attgagggta
    10081 tggtccattc aacatgagtg agacagaaac aattcataaa ggagatgaaa tgtcttgagg
    10141 aatgagctct tagaagaata gttttcaaat gagtgtgcat cacagtcacc tgtaagactt
    10201 attaaaacag atcgctgggc cctacaccca gaggctgtgg ttcagtaggc tgtagtaaac
    10261 cagtaatttg tatttctatg acgttcccag gttctaatgc tgttccccaa ggccacacct
    10321 tggaaaccac cacattaaaa tacccagaag gcattaattc ccagtccttc ctctacacag
    10381 ctgcaaaaca atggtcctga ccatttcatc tttgcactac atccttcact gtctctcttt
    10441 tgcccatagg ataagtacaa actagatctg gttactgcct gccccaccag cctcagcatc
    10501 tctcacaact aggactaact ttttcttctg acaactataa aatatttccc ttgccttctc
    10561 aagtttgctc aaggtcaagt tatgcctttt gcctggaatg acttgacttc tcttttgttt
    10621 tacttagctg gctgcttttc atcttgtagg ttaggtcaag gactccagga agtcttccct
    10681 ggacaagtaa tgaagagggc ataatccaag ggccaactcc catgtttgga acctgactcc
    10741 attttcaggc acgtaatatt gtcaaattcc ttttaaaagc acctgtctgt ctgttaacgt
    10801 tggtgcagat actgctattc ccctcctcca taccattgct gatggttact gagggtatgg
    10861 gaagggccga ctagtccagc tgttcacaaa cagcccttaa tgtcaaactg aatactgcca
    10921 acgtagttcc agtttctgta tctaaagact cagcttggag tcacttgtct ggactaaaag
    10981 taacccctcc ttgtctggtt tgtgactttc tgtactctga tgcccccagc tttctgcctt
    11041 ctagaaattt gtcagaattt ccaaaattct tgggccttcc ttcttgctct atatatggtt
    11101 ttggattcat tccttttaaa aaatatttac tgtcatttca gtagaatttt gacacaataa
    11161 atataagcac atcaga
//
