LOCUS       NM_015052               9453 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens HECT, C2 and WW domain containing E3 ubiquitin protein
            ligase 1 (HECW1), transcript variant 1, mRNA.
ACCESSION   NM_015052
VERSION     NM_015052.5
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 9453)
  AUTHORS   Lin,Y., Gong,H., Liu,J., Hu,Z., Gao,M., Yu,W. and Liu,J.
  TITLE     HECW1 induces NCOA4-regulated ferroptosis in glioma through the
            ubiquitination and degradation of ZNF350
  JOURNAL   Cell Death Dis 14 (12), 794 (2023)
   PUBMED   38049396
  REMARK    GeneRIF: HECW1 induces NCOA4-regulated ferroptosis in glioma
            through the ubiquitination and degradation of ZNF350.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 9453)
  AUTHORS   Haouari,S., Andres,C.R., Lanznaster,D., Marouillat,S., Brulard,C.,
            Dangoumau,A., Ung,D., Veyrat-Durebex,C., Laumonnier,F., Blasco,H.,
            Couratier,P., Corcia,P. and Vourc'h,P.
  CONSRTM   French ALS network FILSLAN
  TITLE     Study of Ubiquitin Pathway Genes in a French Population with
            Amyotrophic Lateral Sclerosis: Focus on HECW1 Encoding the E3
            Ligase NEDL1
  JOURNAL   Int J Mol Sci 24 (2), 1268 (2023)
   PUBMED   36674783
  REMARK    GeneRIF: Study of Ubiquitin Pathway Genes in a French Population
            with Amyotrophic Lateral Sclerosis: Focus on HECW1 Encoding the E3
            Ligase NEDL1.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 9453)
  AUTHORS   Lu,C., Ning,G., Si,P., Zhang,C., Liu,W., Ge,W., Cui,K., Zhang,R.
            and Ge,S.
  TITLE     E3 ubiquitin ligase HECW1 promotes the metastasis of non-small cell
            lung cancer cells through mediating the ubiquitination of Smad4
  JOURNAL   Biochem Cell Biol 99 (5), 675-681 (2021)
   PUBMED   33529121
  REMARK    GeneRIF: E3 ubiquitin ligase HECW1 promotes the metastasis of
            non-small cell lung cancer cells through mediating the
            ubiquitination of Smad4.
REFERENCE   4  (bases 1 to 9453)
  AUTHORS   Wang,C., Dong,K., Wang,Y., Peng,G., Song,X., Yu,Y., Shen,P. and
            Cui,X.
  TITLE     Integrating HECW1 expression into the clinical indicators exhibits
            high accuracy in assessing the prognosis of patients with clear
            cell renal cell carcinoma
  JOURNAL   BMC Cancer 21 (1), 890 (2021)
   PUBMED   34348693
  REMARK    GeneRIF: Integrating HECW1 expression into the clinical indicators
            exhibits high accuracy in assessing the prognosis of patients with
            clear cell renal cell carcinoma.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 9453)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   6  (bases 1 to 9453)
  AUTHORS   Chansard,M., Wang,J., Tran,H.C., Neumayer,G., Shim,S.Y., Park,Y.U.,
            Belzil,C., Le,H.T., Park,S.K. and Nguyen,M.D.
  TITLE     The cytoskeletal protein Ndel1 regulates dynamin 2 GTPase activity
  JOURNAL   PLoS One 6 (1), e14583 (2011)
   PUBMED   21283621
  REMARK    GeneRIF: Ndel1 regulates Dyn2 GTPase activity and impacts
            GluR1-containing membranes distribution in a manner reminiscent of
            Dyn2.
            Publication Status: Online-Only
REFERENCE   7  (bases 1 to 9453)
  AUTHORS   Shinada,K., Tsukiyama,T., Sho,T., Okumura,F., Asaka,M. and
            Hatakeyama,S.
  TITLE     RNF43 interacts with NEDL1 and regulates p53-mediated transcription
  JOURNAL   Biochem Biophys Res Commun 404 (1), 143-147 (2011)
   PUBMED   21108931
  REMARK    GeneRIF: These findings suggest that RNF43 is associated with
            p53-mediated apoptosis in collaboration with NEDL1 in colorectal
            carcinogenesis.
REFERENCE   8  (bases 1 to 9453)
  AUTHORS   Zhang,L., Haraguchi,S., Koda,T., Hashimoto,K. and Nakagawara,A.
  TITLE     Muscle atrophy and motor neuron degeneration in human NEDL1
            transgenic mice
  JOURNAL   J Biomed Biotechnol 2011, 831092 (2011)
   PUBMED   20976258
  REMARK    GeneRIF: These findings suggest that the human NEDL1 transgenic
            mice might develop Amyotrophic lateral sclerosis-like symptoms,
            showing signs of motor abnormalities, accompanied with significant
            reduction in muscle strength.
REFERENCE   9  (bases 1 to 9453)
  AUTHORS   Li,Y., Ozaki,T., Kikuchi,H., Yamamoto,H., Ohira,M. and
            Nakagawara,A.
  TITLE     A novel HECT-type E3 ubiquitin protein ligase NEDL1 enhances the
            p53-mediated apoptotic cell death in its catalytic
            activity-independent manner
  JOURNAL   Oncogene 27 (26), 3700-3709 (2008)
   PUBMED   18223681
  REMARK    GeneRIF: functional interaction of NEDL1 with p53 might contribute
            to the induction of apoptosis in cancerous cells bearing wild-type
            p53.
REFERENCE   10 (bases 1 to 9453)
  AUTHORS   Miyazaki,K., Fujita,T., Ozaki,T., Kato,C., Kurose,Y., Sakamoto,M.,
            Kato,S., Goto,T., Itoyama,Y., Aoki,M. and Nakagawara,A.
  TITLE     NEDL1, a novel ubiquitin-protein isopeptide ligase for
            dishevelled-1, targets mutant superoxide dismutase-1
  JOURNAL   J Biol Chem 279 (12), 11327-11335 (2004)
   PUBMED   14684739
  REMARK    GeneRIF: interaction among misfolded SOD1, NEDL1,
            translocon-associated protein-delta, and Dishevelled-1 forms a
            ubiquitinated protein complex that is included in potentially
            cytotoxic protein aggregates
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            BC151227.1, AK294918.1 and AC011738.4.
            
            On Nov 24, 2018 this sequence version replaced NM_015052.4.
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (a).
            
            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 :: BC151227.1, AB002320.2 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN03465403 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000395891.7/ ENSP00000379228.1
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1766              BC151227.1         49-1814
            1767-2096           AK294918.1         1534-1863
            2097-3361           BC151227.1         2145-3409
            3362-3362           AC011738.4         122288-122288       c
            3363-4153           BC151227.1         3411-4201
            4154-4154           AC011738.4         87460-87460         c
            4155-6466           BC151227.1         4203-6514
            6467-6467           AC011738.4         25733-25733         c
            6468-6791           BC151227.1         6515-6838
            6792-9453           AC011738.4         22747-25408         c
FEATURES             Location/Qualifiers
     source          1..9453
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7p14.1-p13"
     gene            1..9453
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /note="HECT, C2 and WW domain containing E3 ubiquitin
                     protein ligase 1"
                     /db_xref="GeneID:23072"
                     /db_xref="HGNC:HGNC:22195"
                     /db_xref="MIM:610384"
     exon            1..291
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            292..526
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            527..584
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     CDS             558..5378
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /EC_number="2.3.2.26"
                     /note="isoform a is encoded by transcript variant 1;
                     NEDD4-like ubiquitin-protein ligase 1; HECT type E3
                     ubiquitin ligase; E3 ubiquitin-protein ligase HECW1;
                     HECT-type E3 ubiquitin transferase HECW1"
                     /codon_start=1
                     /product="E3 ubiquitin-protein ligase HECW1 isoform a"
                     /protein_id="NP_055867.3"
                     /db_xref="CCDS:CCDS5469.2"
                     /db_xref="GeneID:23072"
                     /db_xref="HGNC:HGNC:22195"
                     /db_xref="MIM:610384"
                     /translation="MLLHLCSVKNLYQNRFLGLAAMASPSRNSQSRRRCKEPLRYSYN
                     PDQFHNMDLRGGPHDGVTIPRSTSDTDLVTSDSRSTLMVSSSYYSIGHSQDLVIHWDI
                     KEEVDAGDWIGMYLIDEVLSENFLDYKNRGVNGSHRGQIIWKIDASSYFVEPETKICF
                     KYYHGVSGALRATTPSVTVKNSAAPIFKSIGADETVQGQGSRRLISFSLSDFQAMGLK
                     KGMFFNPDPYLKISIQPGKHSIFPALPHHGQERRSKIIGNTVNPIWQAEQFSFVSLPT
                     DVLEIEVKDKFAKSRPIIKRFLGKLSMPVQRLLERHAIGDRVVSYTLGRRLPTDHVSG
                     QLQFRFEITSSIHPDDEEISLSTEPESAQIQDSPMNNLMESGSGEPRSEAPESSESWK
                     PEQLGEGSVPDGPGNQSIELSRPAEEAAVITEAGDQGMVSVGPEGAGELLAQVQKDIQ
                     PAPSAEELAEQLDLGEEASALLLEDGEAPASTKEEPLEEEATTQSRAGREEEEKEQEE
                     EGDVSTLEQGEGRLQLRASVKRKSRPCSLPVSELETVIASACGDPETPRTHYIRIHTL
                     LHSMPSAQGGSAAEEEDGAEEESTLKDSSEKDGLSEVDTVAADPSALEEDREEPEGAT
                     PGTAHPGHSGGHFPSLANGAAQDGDTHPSTGSESDSSPRQGGDHSCEGCDASCCSPSC
                     YSSSCYSTSCYSSSCYSASCYSPSCYNGNRFASHTRFSSVDSAKISESTVFSSQDDEE
                     EENSAFESVPDSMQSPELDPESTNGAGPWQDELAAPSGHVERSPEGLESPVAGPSNRR
                     EGECPILHNSQPVSQLPSLRPEHHHYPTIDEPLPPNWEARIDSHGRVFYVDHVNRTTT
                     WQRPTAAATPDGMRRSGSIQQMEQLNRRYQNIQRTIATERSEEDSGSQSCEQAPAGGG
                     GGGGSDSEAESSQSSLDLRREGSLSPVNSQKITLLLQSPAVKFITNPEFFTVLHANYS
                     AYRVFTSSTCLKHMILKVRRDARNFERYQHNRDLVNFINMFADTRLELPRGWEIKTDQ
                     QGKSFFVDHNSRATTFIDPRIPLQNGRLPNHLTHRQHLQRLRSYSAGEASEVSRNRGA
                     SLLARPGHSLVAAIRSQHQHESLPLAYNDKIVAFLRQPNIFEMLQERQPSLARNHTLR
                     EKIHYIRTEGNHGLEKLSCDADLVILLSLFEEEIMSYVPLQAAFHPGYSFSPRCSPCS
                     SPQNSPGLQRASARAPSPYRRDFEAKLRNFYRKLEAKGFGQGPGKIKLIIRRDHLLEG
                     TFNQVMAYSRKELQRNKLYVTFVGEEGLDYSGPSREFFFLLSQELFNPYYGLFEYSAN
                     DTYTVQISPMSAFVENHLEWFRFSGRILGLALIHQYLLDAFFTRPFYKALLRLPCDLS
                     DLEYLDEEFHQSLQWMKDNNITDILDLTFTVNEEVFGQVTERELKSGGANTQVTEKNK
                     KEYIERMVKWRVERGVVQQTEALVRGFYEVVDSRLVSVFDARELELVIAGTAEIDLND
                     WRNNTEYRGGYHDGHLVIRWFWAAVERFNNEQRLRLLQFVTGTSSVPYEGFAALRGSN
                     GLRRFCIEKWGKITSLPRAHTCFNRLDLPPYPSYSMLYEKLLTAVEETSTFGLE"
     exon            585..909
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            910..1017
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            1018..1112
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            1113..1188
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            1189..1358
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            1359..1501
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            1502..1602
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            1603..2955
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            2956..3057
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            3058..3208
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            3209..3348
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            3349..3470
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            3471..3656
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            3657..3791
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            3792..3897
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            3898..3994
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            3995..4078
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            4079..4188
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            4189..4309
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            4310..4423
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            4424..4576
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            4577..4675
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            4676..4805
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            4806..4952
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            4953..5067
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            5068..5266
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     exon            5267..9453
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5611..5616
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /note="hexamer: ATTAAA"
     polyA_site      5631
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /note="major polyA site"
     regulatory      9431..9436
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /note="hexamer: AATAAA"
     polyA_site      9453
                     /gene="HECW1"
                     /gene_synonym="NEDL1"
                     /note="major polyA site"
ORIGIN      
        1 gcatcaggcg ctgttgttgg agccggaaca ccgtgcgact ctgaccgaac cggccccctc
       61 ctcgcgcaca cactcgccga gccgcgcgcg cccctccgcc gtgacagtgg ccgtggcctc
      121 cgctctctcg gggcacccgg cagccagagc gcagcgagag cgggcggtcg ccagggtccc
      181 ctccccagcc agtcccaggc gcccggtgca ctatgcgggg cacgtgcgcc ccccagctct
      241 aatctgcgcg ctgacaggag catgatctgt gcccaggcca gggctgccaa gatatcaatg
      301 ctatgttcag cagaaacgga tacagcaaga gcagcatagt tcaaaaattg agggaggcat
      361 cttctctctt ttcctgggat ttaaacgcga tttaggaggg cagatgccct acccgaaaag
      421 gccaaccgtt aaagaccccg gcagtgttgt ggtccaaggc gtctcaaagc aggtggccag
      481 atctgcgttt ctcatcagca gactcactcc ggctgtggct attacggaat tgatgcgcgt
      541 acacgtggtg ggtcattatg ctgctgcacc tgtgtagtgt gaagaatctg taccagaaca
      601 ggtttttagg cctggccgcc atggcgtctc cttctagaaa ctcccagagc cgacgccggt
      661 gcaaggagcc gctccgatac agctacaacc ccgaccagtt ccacaacatg gacctcaggg
      721 gcggccccca cgatggcgtc accattcccc gctccaccag cgacactgac ctggtcacct
      781 cggacagccg ctccacgctc atggtcagca gctcctacta ttccatcggg cactctcagg
      841 acctggtcat ccactgggac ataaaggagg aagtggacgc tggggactgg attggcatgt
      901 acctcattga tgaggtcttg tccgaaaact ttctggacta taaaaaccgt ggagtcaatg
      961 gttctcatcg gggccagatc atctggaaga tcgatgccag ctcgtacttt gtggaacctg
     1021 aaactaagat ctgcttcaaa tactaccatg gagtgagtgg ggccctgcga gcaaccaccc
     1081 ccagtgtcac ggtcaaaaac tcggcagctc ctatttttaa aagcattggt gctgatgaga
     1141 ccgtccaagg acaaggaagt cggaggctga tcagcttctc tctctcagat ttccaagcca
     1201 tggggttgaa gaaagggatg tttttcaacc cagaccctta tctgaagatt tccattcagc
     1261 ctgggaaaca cagcatcttc cccgccctcc ctcaccatgg acaggagagg agatccaaga
     1321 tcataggcaa caccgtgaac cccatctggc aggccgagca attcagtttt gtgtccttgc
     1381 ccactgacgt gctggaaatt gaggtgaagg acaagtttgc caagagccgc cccatcatca
     1441 agcgcttctt gggaaagctg tcgatgcccg ttcaaagact cctggagaga cacgccatag
     1501 gggatagggt ggtcagctac acacttggcc gcaggcttcc aacagatcat gtgagtggac
     1561 agctgcaatt ccgatttgag atcacttcct ccatccaccc agatgatgag gagatttccc
     1621 tgagtaccga gcctgagtca gcccaaattc aggacagccc catgaacaac ctgatggaaa
     1681 gcggcagtgg ggaacctcgg tctgaggcac cagagtcctc tgagagctgg aagccagagc
     1741 agctgggtga gggcagtgtc cccgatggtc cagggaacca aagcatagag ctttccagac
     1801 cagctgagga agcagcagtc atcacggagg caggagacca gggcatggtc tctgtgggac
     1861 ctgaaggggc tggggagctc ctggcccagg tgcaaaagga catccagcct gcccccagtg
     1921 cagaagagct ggccgagcag ctggacctgg gtgaggaggc atcagcactg ctgctggaag
     1981 acggtgaagc cccagccagc accaaggagg agcccttgga ggaggaagca acgacccaga
     2041 gccgggctgg aagggaagaa gaggagaagg agcaggagga ggagggagat gtgtctaccc
     2101 tggagcaggg agagggcagg ctgcagctgc gggcctcggt gaagagaaaa agcaggccct
     2161 gctccttgcc tgtgtccgag ctggagacgg tgatcgcgtc agcctgcggg gaccccgaga
     2221 ccccgcggac acactacatc cgcatccaca ccctgctgca cagcatgccc tccgcccagg
     2281 gcggcagcgc ggcagaggag gaggacggcg cggaggagga gtccaccctc aaggactcct
     2341 cggagaagga tgggctcagc gaggtggaca cggtggccgc tgacccgtct gccctggaag
     2401 aggacagaga agagcccgag ggggctactc caggcacggc gcaccctggc cactccgggg
     2461 gccacttccc cagcctggcc aatggcgcgg cccaggatgg cgacacgcac cccagcaccg
     2521 ggagcgagag cgactccagc cccaggcaag gcggggacca cagttgcgag ggctgtgacg
     2581 cgtcctgctg cagcccctcg tgctacagct cctcgtgcta cagcacgtcc tgctacagca
     2641 gctcgtgcta cagcgcctcg tgctacagcc cctcctgcta caacggcaac aggttcgcca
     2701 gccacacgcg cttctcctcc gtggacagcg ccaagatctc cgagagcacg gtcttctcct
     2761 cgcaagacga cgaggaggag gagaacagcg cgttcgagtc ggtacccgac tccatgcaga
     2821 gccctgagct ggacccggag tccacgaacg gcgctgggcc gtggcaagac gagctggccg
     2881 cccctagcgg gcacgtggaa agaagcccgg aaggtctgga atcccccgtg gcaggtccaa
     2941 gcaatcggag agaaggtgaa tgtcctatac tccataattc ccagccagta agccagcttc
     3001 cttccctgag gcctgaacat catcactacc caacaatcga tgagcctctt ccaccaaact
     3061 gggaagctcg aattgacagc cacgggcggg tcttttatgt ggaccacgtg aaccgcacaa
     3121 ccacctggca gcgtccgacg gcagcagcca ccccggatgg catgcggaga tcggggtcca
     3181 tccagcagat ggagcaactc aacaggcggt atcaaaacat tcagcgaacc attgcaacag
     3241 agaggtccga agaagattct ggcagccaaa gctgcgagca agccccagca ggaggaggcg
     3301 gaggtggagg gagtgactca gaagccgaat cttcccagtc cagcttagat ctaaggagag
     3361 aagggtcact ttctccagtg aactcacaaa aaatcacctt gctgctgcag tccccagcgg
     3421 tcaagttcat caccaacccc gagttcttca ctgtgctaca tgccaattat agtgcctacc
     3481 gagtcttcac cagtagcacc tgcttaaagc acatgattct gaaagtccga cgggatgctc
     3541 gcaattttga acgctaccag cacaaccggg acttggtgaa tttcatcaac atgttcgcag
     3601 acactcggct ggaactgccc cggggctggg agatcaaaac ggaccagcag ggaaagtctt
     3661 ttttcgtgga ccacaacagt cgagctacca ctttcattga cccccgaatc cctcttcaga
     3721 acggtcgtct tcccaatcat ctaactcacc gacagcacct ccagaggctc cgaagttaca
     3781 gcgctggaga ggcctcagaa gtttctagaa acagaggagc ctctttactg gccaggccag
     3841 gacacagctt agtagctgct attcgaagcc aacatcaaca tgagtcattg ccactggcat
     3901 ataatgacaa gattgtggca tttcttcgcc agccaaacat ttttgaaatg ctgcaagagc
     3961 gtcagccaag cttagcaaga aaccacacac tcagggagaa aatccattac attcggactg
     4021 agggtaatca cgggcttgag aagttgtcct gtgatgcgga tctggtcatt ttgctgagtc
     4081 tctttgaaga agagattatg tcctacgtcc ccctgcaggc tgccttccac cctgggtata
     4141 gcttctctcc ccgatgttca ccctgttctt cacctcagaa ctccccaggt ttacagagag
     4201 ccagtgcaag agccccttcc ccctaccgaa gagactttga ggccaagctc cgcaatttct
     4261 acagaaaact ggaagccaaa ggatttggtc agggtccggg gaaaattaag ctcattattc
     4321 gccgggatca tttgttggag ggaaccttca atcaggtgat ggcctattcg cggaaagagc
     4381 tccagcgaaa caagctctac gtcacctttg ttggagagga gggcctggac tacagtggcc
     4441 cctcgcggga gttcttcttc cttctgtctc aggagctctt caacccttac tatggactct
     4501 ttgagtactc ggcaaatgat acttacacgg tgcagatcag ccccatgtcc gcatttgtag
     4561 aaaaccatct tgagtggttc aggtttagcg gtcgcatcct gggtctggct ctgatccatc
     4621 agtaccttct tgacgctttc ttcacgaggc ccttctacaa ggcactcctg agactgccct
     4681 gtgatttgag tgacctggaa tatttggatg aggaattcca ccagagtttg cagtggatga
     4741 aggacaacaa catcacagac atcttagacc tcactttcac tgttaatgaa gaggtttttg
     4801 gacaggtcac ggaaagggag ttgaagtctg gaggagccaa cacacaggtg acggagaaaa
     4861 acaagaagga gtacatcgag cgcatggtga agtggcgggt ggagcgcggc gtggtacagc
     4921 agaccgaggc gctggtgcgc ggcttctacg aggttgtaga ctcgaggctg gtgtccgtgt
     4981 ttgatgccag ggagctggag ctggtgatag ctggcaccgc ggaaatcgac ctaaatgact
     5041 ggcggaataa cactgagtac cggggaggtt accacgatgg gcatcttgtg atccgctggt
     5101 tctgggctgc ggtggagcgc ttcaataatg agcagaggct gagattactg cagtttgtca
     5161 cgggaacatc cagcgtgccc tacgaaggct tcgcagccct ccgtgggagc aatgggcttc
     5221 ggcgcttctg catagagaaa tgggggaaaa ttacttctct ccccagggca cacacatgct
     5281 tcaaccgact ggatcttcca ccgtatccct cgtactccat gttgtatgaa aagctgttaa
     5341 cagcagtaga ggaaaccagc acctttggac ttgagtgagg acatggaacc tcgcctgaca
     5401 ttttcctggc cagtgacatc acccttcctg ggatgatccc cttttccctt tcccttaatc
     5461 aactctcctt tgattttggt attccatgat ttttattttc aaaccaaatc aggattgaca
     5521 aaagctgtgc atgaagaact gccttcttct aagatctaac cttcaggctt ctctcctctg
     5581 ttttcaatga actgctagcc tgtatgcaat attaaaaaac agctgtctca aggtctgtgt
     5641 atatctccac atacctccat tactaacaat gaaatatgaa tgcaagttaa gctacacttg
     5701 accaaatggt aataaatgtt tacttccatt tctatcattg aagggaaaat gtgagcatta
     5761 agcactccag gctttcatat gcccatgtct tctgagcaga gccaccattt tttataattt
     5821 ctaataacca actccagaac taggagctga tcaactcttt gttttcctct ccatctactt
     5881 ttccctgtgc ataatatcca tccaaaggac aacagtggca aagctgaaat ttttatacat
     5941 tcaactcatg attcacatgt ggcatcagtc ccatcagccg gaactagcct agacatacgg
     6001 tgcaaatatg acacttctaa cgattaacaa cagcaagaaa acacctgctg ctgatgcaat
     6061 gcaatgcatc ccaatggttg tggggattgt gggctcaact caagagaagt ttaggagggg
     6121 gagcatccct agtgaatact cacaccacaa gaaggacaaa cttgtgcaca tgtccaagaa
     6181 agaaagcttc ttgattgagg tagcatgaag gatgaggctt cagcccccat tgtcttatgt
     6241 agaatgtggc aatgccaact ggagaaaggg aagaaggaca tattaccttg gtttgaatcc
     6301 ctgagttctg tactgttctg ttttgtttag tctagccaca gttcttcaca aaggaaaaaa
     6361 aaatgtgtag atgataccat gacttttgtt aaagccatga cttttgtttg cttggcagac
     6421 aaaccctttt tttaaaactt tgatattttt ttttcacatt tttttttcct tttcctttct
     6481 taatcatgga gttcaagttc ctttgcattc gattgtccat cgggaccaca ctaggaagct
     6541 gcagagagtg atggtgcttg ttagggatca agggcaacat agtacttctc cttcacccat
     6601 agtaatcctc ctggggcaga aacataacac cccaaaggca cgttgatttg tatcaaaata
     6661 aatatccagt ttcttttagc attcagtgaa aacatatctc agaaaacttc atgttgtcag
     6721 aaaaacagct gcaggctcca aagacagcct aacctctcaa ctacatttga aataaaccca
     6781 accataatgg tcatttgcta tttttctaac gttgttatcc atgttgcctg aaataggtca
     6841 taaatgaaag tgtttttctt cactgggaaa aagaagagct caagagaccc cactatttaa
     6901 atgtcattta attgttttcc atattaaaac aagggagaaa tgtaagacga agtgaatttc
     6961 atatgaagcc aatggctcat tataccagtt tgtgtctgga cagtgtgtta tttgtgttcc
     7021 tacactctaa agcattccgg ccaggagcgg tggctcatgc ctgtaatccc agcactttgg
     7081 gaggccgagg tggggagatc gcttgaggtc aggagttcaa gacaagcctg gccaacatgg
     7141 tgaaacccca tctctactaa aaatacaaaa attagccggg cgtgatggca catgccggta
     7201 gtcccagcta cttgggaggc tgaggaagga gaatcgctca aacctgagaa gcagaggttg
     7261 cagtgagcca agactgtgcc actgcactcc agcctggatg atcaagggag acaccatcta
     7321 aaaaaaaaat aaataaaaat aaaagcattt ttttagtagg aattatctac aatgcccagc
     7381 accccttgca gcgatgtgtc cgttgtcaat caaggagtat acattataga aatttagact
     7441 tttattgtct aaaaagaata tttactgaga caggatggaa tctgtaagtt atatgatata
     7501 gaatttgagg gatatgtaaa attcagtaca cgttcagcat ctgaaaaata atggattcca
     7561 atggagctat tgttttattt atgaaatcag agcataagga ctatgcaaat cattgaacca
     7621 taaccttatt ctaactcttg caacaacatc tctaatatag gggcatcttt tatctttaga
     7681 acttggtgtt atatatatgt aaatactcat taattcaagc actctctttc tagtactcac
     7741 attatttgtc aggcattgga aaaggagaaa gctgtttaca agatggacca gctcctggag
     7801 agctttgcaa tttatataaa ttactaatta atctattaat tagattaatt aatatctaat
     7861 ctacccatat acaaaaggaa tgcagtatct cagaaattat atatagatag gtaactttgg
     7921 catacatgat ttttcaacta ccgtttcctt atccaccagt actactgatg tcacagctat
     7981 agatctatcc cacaaagcat aacaggaaca ttctttcaca aaagtgcaaa atttcatgaa
     8041 gaaatgctga tgtcacggtc acctgaaaga agatgaagct tgtaatattt tattgcaacc
     8101 ttgcatagaa tccttaagga agaaaaacaa agagaagagg aacacagaaa caagttatgg
     8161 aaattcatgt ttaccttatt tataaggctg atttttaaat tatatataat ttttcattca
     8221 atatgtatat gaaatgaaat agctatagaa ctaaatttca cttaggtgga ggtataaacc
     8281 accttaaatt atatagttcg gcagaaagac agatctattt gttaccacct gtaatttttt
     8341 tttaagcatg agttttctcc atggaggcaa attgcaaaat taatcactta taaatttata
     8401 agccacaatc tccctaaaac aattgatttt agtaagagtg taacgccttt aatcagggga
     8461 caaacaagaa caataaataa gagaagattt atgttacaac tttgaaaaat gcttttaaaa
     8521 ttctataaag tgttataata atttcatgga tatcacaaat gttttattct acagtgtgaa
     8581 gatgataatc ctaaaaatgg aaattgattc tgtgaggtca ggagaagtat tctaaatcta
     8641 ctgaactctt tgtaatttcc tatgtatata aatgagtgga ggttgtgaag atgccgagag
     8701 agtggtgaaa aaattaagaa aaagagacat atgatttggg ggagcaggcg ttaaacatgc
     8761 aagatctaaa ttttctttta atacatgacc atatgtcctt gaacagtaag tatatttgtg
     8821 tggcaagcca atggctgagt tttccagggt agttttaata ttacatccat catattttca
     8881 gtccatgtgt caaaccatgt gtccaaaatt tgggttcgga aatttctcag ttgccacaaa
     8941 tattttccca gtcaagatga aacactttca aatgaaagta gttagaactt tacataacaa
     9001 atgtggtgct ttattattat tattattatt atttttatta ttattattat tacgtacttc
     9061 agtgttcatt attaaaacta ccgcaatact atatcataaa aatctgggat ggatgttcca
     9121 gccatcataa ggtccaaaag aaaagagaaa gtgttatttt cctgttagtg acatgtagtc
     9181 cctttgttct agtaggaaaa aaggtgccta gaggtagtat atagagtaaa tattgttcct
     9241 ttagcctact tcctgcagct tccaatttat ccaaggaaat gtctacaaca attttgttca
     9301 aaagtctgtt ctagtcaata gcaggagaag tccacgttat tgggctgatt ttgcttacat
     9361 cagcaagaga aatgtcacgt gatactcagg ccgcgctttc tcttccatca caccatcttc
     9421 aaggaatgtc aataaactca ctttggtatg gca
//
