LOCUS       NM_018227               9540 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens ubiquitin like modifier activating enzyme 6 (UBA6),
            mRNA.
ACCESSION   NM_018227
VERSION     NM_018227.6
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 9540)
  AUTHORS   Lee,D., Lee,P.C. and Hong,J.H.
  TITLE     UBA6 Inhibition Accelerates Lysosomal TRPML1 Depletion and Exosomal
            Secretion in Lung Cancer Cells
  JOURNAL   Int J Mol Sci 25 (5), 2843 (2024)
   PUBMED   38474091
  REMARK    GeneRIF: UBA6 Inhibition Accelerates Lysosomal TRPML1 Depletion and
            Exosomal Secretion in Lung Cancer Cells.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 9540)
  AUTHORS   Traeger,L., Wiegand,S.B., Sauer,A.J., Corman,B.H.P., Peneyra,K.M.,
            Wunderer,F., Fischbach,A., Bagchi,A., Malhotra,R., Zapol,W.M. and
            Bloch,D.B.
  TITLE     UBA6 and NDFIP1 regulate the degradation of ferroportin
  JOURNAL   Haematologica 107 (2), 478-488 (2022)
   PUBMED   34320783
  REMARK    GeneRIF: UBA6 and NDFIP1 regulate the degradation of ferroportin.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 9540)
  AUTHORS   Chen,Z., Liu,J., Chen,Q., Su,M., Lu,H., Yang,Y., Zhou,G., Zhang,X.,
            Liu,Y., Dong,W. and Fang,Q.
  TITLE     Down-regulation of UBA6 exacerbates brain injury by inhibiting the
            activation of Notch signaling pathway to promote cerebral cell
            apoptosis in rat acute cerebral infarction model
  JOURNAL   Mol Cell Probes 53, 101612 (2020)
   PUBMED   32497710
  REMARK    GeneRIF: Down-regulation of UBA6 exacerbates brain injury by
            inhibiting the activation of Notch signaling pathway to promote
            cerebral cell apoptosis in rat acute cerebral infarction model.
            Erratum:[Mol Cell Probes. 2021 Dec;60:101773. doi:
            10.1016/j.mcp.2021.101773.. PMID: 34649757]
REFERENCE   4  (bases 1 to 9540)
  AUTHORS   Hu,Y., Bai,X., Zhang,C., Chakrabarti,S., Tang,B., Xiong,H.,
            Wang,Z., Yu,G., Xu,C., Chen,Q. and Wang,Q.K.
  TITLE     Ubiquitination-activating enzymes UBE1 and UBA6 regulate
            ubiquitination and expression of cardiac sodium channel Nav1.5
  JOURNAL   Biochem J 477 (9), 1683-1700 (2020)
   PUBMED   32315024
  REMARK    GeneRIF: Ubiquitination-activating enzymes UBE1 and UBA6 regulate
            ubiquitination and expression of cardiac sodium channel Nav1.5.
REFERENCE   5  (bases 1 to 9540)
  AUTHORS   Jia,R. and Bonifacino,J.S.
  TITLE     Negative regulation of autophagy by UBA6-BIRC6-mediated
            ubiquitination of LC3
  JOURNAL   Elife 8, e50034 (2019)
   PUBMED   31692446
  REMARK    GeneRIF: These findings demonstrate that UBA6 and BIRC6 negatively
            regulate autophagy by limiting the availability of LC3B.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 9540)
  AUTHORS   Groettrup,M., Pelzer,C., Schmidtke,G. and Hofmann,K.
  TITLE     Activating the ubiquitin family: UBA6 challenges the field
  JOURNAL   Trends Biochem Sci 33 (5), 230-237 (2008)
   PUBMED   18353650
  REMARK    GeneRIF: Ubiquitin-like modifier activating enzyme 6 activates not
            only ubiquitin, but also the ubiquitin-like modifier FAT10[review]
            Review article
REFERENCE   7  (bases 1 to 9540)
  AUTHORS   Chiu,Y.H., Sun,Q. and Chen,Z.J.
  TITLE     E1-L2 activates both ubiquitin and FAT10
  JOURNAL   Mol Cell 27 (6), 1014-1023 (2007)
   PUBMED   17889673
  REMARK    GeneRIF: The identification of an E1-like protein, termed E1-L2,
            that activates both ubiquitin and another ubiquitin-like protein,
            FAT10, is reported.
REFERENCE   8  (bases 1 to 9540)
  AUTHORS   Pelzer,C., Kassner,I., Matentzoglu,K., Singh,R.K., Wollscheid,H.P.,
            Scheffner,M., Schmidtke,G. and Groettrup,M.
  TITLE     UBE1L2, a novel E1 enzyme specific for ubiquitin
  JOURNAL   J Biol Chem 282 (32), 23010-23014 (2007)
   PUBMED   17580310
  REMARK    GeneRIF: UBE1L2 is a novel E1 enzyme specific for ubiquitin
REFERENCE   9  (bases 1 to 9540)
  AUTHORS   Jin,J., Li,X., Gygi,S.P. and Harper,J.W.
  TITLE     Dual E1 activation systems for ubiquitin differentially regulate E2
            enzyme charging
  JOURNAL   Nature 447 (7148), 1135-1138 (2007)
   PUBMED   17597759
  REMARK    GeneRIF: Human Uba6 and Ube1 have distinct preferences for E2
            charging in vitro, and their specificity depends in part on their
            C-terminal ubiquitin-fold domains, which recruit E2s
REFERENCE   10 (bases 1 to 9540)
  AUTHORS   Zhu,H., Zhou,Z.M., Huo,R., Huang,X.Y., Lu,L., Lin,M., Wang,L.R.,
            Zhou,Y.D., Li,J.M. and Sha,J.H.
  TITLE     Identification and characteristics of a novel E1 like gene nUBE1L
            in human testis
  JOURNAL   Acta Biochim Biophys Sin (Shanghai) 36 (3), 227-234 (2004)
   PUBMED   15202508
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            BC126484.1, AY359880.1, AL832015.2, AW451445.1, BM973988.1 and
            AC096720.3.
            
            On Nov 22, 2018 this sequence version replaced NM_018227.5.
            
            Summary: Modification of proteins with ubiquitin (UBB; MIM 191339)
            or ubiquitin-like proteins controls many signaling networks and
            requires a ubiquitin-activating enzyme (E1), a ubiquitin
            conjugating enzyme (E2), and a ubiquitin protein ligase (E3).
            UBE1L2 is an E1 enzyme that initiates the activation and
            conjugation of ubiquitin-like proteins (Jin et al., 2007 [PubMed
            17597759]).[supplied by OMIM, Mar 2008].
            
            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 :: SRR1660809.92861.1, AL832015.2
                                           [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000350]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000322244.10/ ENSP00000313454.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-3645              BC126484.1         12-3656
            3646-4911           AY359880.1         2983-4248
            4912-5382           AL832015.2         4895-5365
            5383-5882           AW451445.1         8-507               c
            5883-6431           BM973988.1         16-564              c
            6432-9540           AC096720.3         13342-16450         c
FEATURES             Location/Qualifiers
     source          1..9540
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q13.2"
     gene            1..9540
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /note="ubiquitin like modifier activating enzyme 6"
                     /db_xref="GeneID:55236"
                     /db_xref="HGNC:HGNC:25581"
                     /db_xref="MIM:611361"
     exon            1..107
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     CDS             37..3195
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /EC_number="6.2.1.45"
                     /note="ubiquitin-activating enzyme E1-like 2; UBA6,
                     ubiquitin-activating enzyme E1; monocyte protein 4;
                     ubiquitin-activating enzyme 6; ubiquitin-activating enzyme
                     E1-like protein 2"
                     /codon_start=1
                     /product="ubiquitin-like modifier-activating enzyme 6"
                     /protein_id="NP_060697.4"
                     /db_xref="CCDS:CCDS3516.1"
                     /db_xref="GeneID:55236"
                     /db_xref="HGNC:HGNC:25581"
                     /db_xref="MIM:611361"
                     /translation="MEGSEPVAAHQGEEASCSSWGTGSTNKNLPIMSTASVEIDDALY
                     SRQRYVLGDTAMQKMAKSHVFLSGMGGLGLEIAKNLVLAGIKAVTIHDTEKCQAWDLG
                     TNFFLSEDDVVNKRNRAEAVLKHIAELNPYVHVTSSSVPFNETTDLSFLDKYQCVVLT
                     EMKLPLQKKINDFCRSQCPPIKFISADVHGIWSRLFCDFGDEFEVLDTTGEEPKEIFI
                     SNITQANPGIVTCLENHPHKLETGQFLTFREINGMTGLNGSIQQITVISPFSFSIGDT
                     TELEPYLHGGIAVQVKTPKTVFFESLERQLKHPKCLIVDFSNPEAPLEIHTAMLALDQ
                     FQEKYSRKPNVGCQQDSEELLKLATSISETLEEKPDVNADIVHWLSWTAQGFLSPLAA
                     AVGGVASQEVLKAVTGKFSPLCQWLYLEAADIVESLGKPECEEFLPRGDRYDALRACI
                     GDTLCQKLQNLNIFLVGCGAIGCEMLKNFALLGVGTSKEKGMITVTDPDLIEKSNLNR
                     QFLFRPHHIQKPKSYTAADATLKINSQIKIDAHLNKVCPTTETIYNDEFYTKQDVIIT
                     ALDNVEARRYVDSRCLANLRPLLDSGTMGTKGHTEVIVPHLTESYNSHRDPPEEEIPF
                     CTLKSFPAAIEHTIQWARDKFESSFSHKPSLFNKFWQTYSSAEEVLQKIQSGHSLEGC
                     FQVIKLLSRRPRNWSQCVELARLKFEKYFNHKALQLLHCFPLDIRLKDGSLFWQSPKR
                     PPSPIKFDLNEPLHLSFLQNAAKLYATVYCIPFAEEDLSADALLNILSEVKIQEFKPS
                     NKVVQTDETARKPDHVPISSEDERNAIFQLEKAILSNEATKSDLQMAVLSFEKDDDHN
                     GHIDFITAASNLRAKMYSIEPADRFKTKRIAGKIIPAIATTTATVSGLVALEMIKVTG
                     GYPFEAYKNCFLNLAIPIVVFTETTEVRKTKIRNGISFTIWDRWTVHGKEDFTLLDFI
                     NAVKEKYGIEPTMVVQGVKMLYVPVMPGHAKRLKLTMHKLVKPTTEKKYVDLTVSFAP
                     DIDGDEDLPGPPVRYYFSHDTD"
     exon            108..170
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            171..265
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            266..294
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            295..389
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            390..501
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            502..582
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            583..705
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            706..829
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            830..933
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            934..996
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            997..1073
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            1074..1140
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            1141..1284
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            1285..1352
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            1353..1431
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            1432..1512
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            1513..1590
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            1591..1772
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            1773..1878
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            1879..1968
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            1969..2049
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            2050..2178
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            2179..2230
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            2231..2294
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            2295..2364
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            2365..2436
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            2437..2554
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            2555..2748
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            2749..2876
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            2877..2964
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            2965..3059
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            3060..9540
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4889..4894
                     /regulatory_class="polyA_signal_sequence"
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /note="hexamer: AATAAA"
     polyA_site      4911
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /note="major polyA site"
     regulatory      5367..5372
                     /regulatory_class="polyA_signal_sequence"
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /note="hexamer: AATAAA"
     polyA_site      5388
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
     regulatory      9515..9520
                     /regulatory_class="polyA_signal_sequence"
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
                     /note="hexamer: AATAAA"
     polyA_site      9540
                     /gene="UBA6"
                     /gene_synonym="E1-L2; MOP-4; UBE1L2"
ORIGIN      
        1 accttccagt agccggcggc ggtgtctcag gcggcaatgg aaggatccga gcctgtggcc
       61 gcccatcagg gggaagaggc gtcctgttct tcctggggga ctggcagcac aaataaaaat
      121 ttgcccatta tgtcaacagc atctgtggaa atcgatgatg cattgtatag tcgacagagg
      181 tacgttcttg gagacacagc aatgcagaag atggccaagt cccatgtttt cttaagtggg
      241 atgggtggtc ttggtttgga aattgcaaag aatcttgttc ttgcagggat taaggcagtt
      301 acaattcatg atacagaaaa atgccaagca tgggatctag gaaccaactt ctttctcagt
      361 gaagatgatg ttgttaataa gagaaacagg gctgaagctg tacttaaaca tattgcagaa
      421 ctaaatccat acgttcatgt cacatcatct tctgttcctt tcaatgagac cacagatctc
      481 tcctttttag ataaatacca gtgtgtagta ttgactgaga tgaaacttcc attgcagaag
      541 aagatcaatg acttttgccg ttctcagtgc cctccaatta agtttatcag tgcagatgta
      601 catggaattt ggtcaaggtt attttgtgat ttcggtgatg aatttgaagt tttagataca
      661 acaggagaag aaccaaaaga aattttcatt tcaaacataa cgcaagcaaa tcctggcatt
      721 gttacttgcc ttgaaaatca tcctcacaaa ctggagacag gacaattcct aacatttcga
      781 gaaattaatg gaatgacagg tttaaatgga tctatacaac aaataacggt gatatcgcca
      841 ttttctttta gtattggtga caccacagaa ctggaaccat atttacatgg aggcatagct
      901 gtccaagtta agactcctaa aacagttttt tttgaatcac tggagaggca gttaaaacat
      961 ccaaagtgcc ttattgtgga ttttagcaac cctgaggcac ctttagagat tcacacagct
     1021 atgcttgcct tggaccagtt tcaggagaaa tacagtcgca agccaaatgt tggatgccaa
     1081 caagattcag aagaactgtt gaaactagca acatctataa gtgaaacctt ggaagagaag
     1141 cctgatgtaa atgctgacat tgtgcattgg ctctcttgga ctgcccaagg ctttttatct
     1201 ccacttgctg cagcagtagg aggtgttgcc agccaagaag tattgaaagc tgtaacagga
     1261 aaattttctc ctttgtgcca gtggttatat cttgaagcag cagatattgt tgaatcacta
     1321 ggcaaacctg aatgtgaaga atttctccca cgaggagata gatatgatgc cttaagagct
     1381 tgcattggag acactttgtg tcagaaactg caaaatttaa acatcttctt agtagggtgt
     1441 ggagccatag gctgtgaaat gttgaaaaat tttgctttac ttggtgttgg cacaagcaaa
     1501 gagaaaggaa tgattacagt tacagatcct gacttgatag agaaatccaa cttaaataga
     1561 cagttcctat ttcgtcctca tcacatacag aaacctaaaa gctacactgc tgctgatgct
     1621 actctgaaaa taaattctca aataaagata gatgcacacc tgaacaaagt atgtccaacc
     1681 actgagacca tttacaatga tgagttctat actaaacaag atgtaattat tacagcatta
     1741 gataatgtgg aagccaggag atacgtagac agtcgttgct tagcaaatct aaggcctctt
     1801 ttagattctg gaacaatggg cactaaggga cacactgaag ttattgtacc gcatttgact
     1861 gagtcttaca atagtcatcg ggatccccca gaagaggaaa taccattttg tactctaaaa
     1921 tcctttccag ctgctattga acataccata cagtgggcaa gagataagtt tgaaagttcc
     1981 ttttcccaca aaccttcatt gtttaacaaa ttttggcaaa cctattcatc tgcagaagaa
     2041 gtcttacaga agatacagag tggacacagt ttagaaggct gttttcaagt tataaagtta
     2101 cttagcagaa gacctagaaa ttggtcccag tgtgtagaat tagcaagatt aaagtttgaa
     2161 aaatatttta accataaggc tcttcagctt cttcactgtt tccctctgga catacgatta
     2221 aaagatggca gtttattttg gcagtcacca aagaggccac cctctccaat aaaatttgat
     2281 ttaaatgagc ctttgcacct cagtttcctt cagaatgctg caaaactata tgctacagta
     2341 tattgtattc catttgcaga agaggactta tcagcagatg ccctcttgaa tattctttca
     2401 gaagtaaaga ttcaggaatt caagccttcc aataaggttg ttcaaacaga tgaaactgca
     2461 aggaaaccag accatgttcc tattagcagt gaagatgaga ggaatgcaat tttccaacta
     2521 gaaaaggcta ttttatctaa tgaagccacc aaaagtgacc ttcagatggc agtgctttca
     2581 tttgaaaaag atgatgatca taatggacac atagatttca tcacagctgc atcaaatctt
     2641 cgtgccaaaa tgtacagcat tgaaccagct gaccgtttca aaacaaagcg catagctggt
     2701 aaaattatac ctgctatagc aacaaccact gctacagttt ctggcttggt tgccttggag
     2761 atgatcaaag taactggtgg ctatccattt gaagcttaca aaaattgttt tcttaactta
     2821 gccattccaa ttgtagtatt tacagagaca actgaagtaa ggaaaactaa aatcagaaat
     2881 ggaatatcat ttacaatttg ggatcgatgg accgtacatg gaaaagaaga tttcaccctc
     2941 ttggatttca taaatgcagt caaagagaag tatggaattg agccaacaat ggtggtacag
     3001 ggagtcaaaa tgctttatgt tcctgtaatg cctggtcatg caaaaagatt gaagttaaca
     3061 atgcataaac ttgtaaaacc tactactgaa aagaaatatg tggatcttac tgtgtcattt
     3121 gctccagaca ttgatggaga tgaagatttg ccgggacctc cagtaagata ctacttcagt
     3181 catgacactg attaatacaa gttgtcttaa cgttactcca ggaccacttg attttggaaa
     3241 gagtgcactt aattcagaag ctaaagaaaa tcagttcata atactatgga tttctctttc
     3301 attaagcctt aattttaagg gaaacatcag taagaaactg cactgaagaa ttataaaaca
     3361 ttttggggca tagcatacac ttgtctaacg gttcacacgt ggctatgatc acaagcaact
     3421 ttgaactgga atgctattta caaaagtttt gtgtattaat ctgtgtatta atctctctgg
     3481 ataaaaagaa ggaaaaaata tgtatgacca gaacagatat ggatgaagaa attgaaagca
     3541 acgaatgcaa ctattcaaaa agtttaattt tatgaatttc ttttttgttt agtcttgaag
     3601 actgattttc tatgcaaata gtgtttggca tcctgcacct ctgatatgat ttggctttga
     3661 gaatttaata ccactgggaa gaagtatggt agtggtggat gaagggtgga tattttaaat
     3721 tgtgcagtta cagtttactg tcctattacc tctgctcgtt taaccagttt gttatatcac
     3781 tgtgtcccca aaatcaggat ttttgttgat agcatcagtg ttgtaggagc aataggtcag
     3841 atgagacata ttaacttaga ctaaacgtga acagtattat atggactctc acaacgctct
     3901 tagagaatcc gtgaatgtga acagacaaat gtggctaacc atttgattct tcagtatgcc
     3961 ttctaatgtg gctattttat ttatgtgaga ctctaaacct gattgtccta atatataaaa
     4021 ctaaaagatt ttgtaaaggg agtgtcttta gaaatagatg aaatgtagaa tgttaaaaat
     4081 tattgctagg gtagtctttt ttttttccag aaacctaatt agggtattaa attttgtgtt
     4141 ttttttgttt ttttttttta aacagaagca tgttatttca ttcccattcc cagaaaggga
     4201 gttaatgaag ataaaaattt attttttaag gtctttattg agagaaactt tgttttctga
     4261 tatgaactat tgcagatgtt tttataaata ctttcattaa aatgatgtaa acagtagtac
     4321 ccaacactgt aaactcagtg aaaatagtaa atgattcttt tattactaag actgtcatgc
     4381 attctgaagc agttggcttt tttttaacca taggaagtaa tttccctcta gctcctttcc
     4441 ttctactctc ctgctcagac cattagtagg tactttgtta aataaaaaac tagattaaca
     4501 tcaatattac tccaatttgg tatcttttac actatgtatt atacctactt tctttttatt
     4561 tcatttacaa atagtttaaa ttactttatc aaccagctgt attgtttccc tcttgtaaaa
     4621 gtaccatcaa gtggggaaaa tgtatgtgga agtggagagt gaatttgtat gactaaagga
     4681 taatctgtac atggggaagt gggcaaaagt ggataggatg aatttaaaga aaatgactac
     4741 ctttggaaaa aagaaattaa attttgttca catatcctac cctttcccat tgtgcatatc
     4801 ccaagtgtca tatttaaaac taaggttact taaaacagaa tccaggaata tcaaggctct
     4861 gtggcttgga attttagagg ataggactaa taaaaggact tttgcaaaga aggctttttt
     4921 ccacgttcac tttgttttgt gttctttgaa agtaactgat acttttcggg tagttaattc
     4981 agcagtccat aaatatgatc cagtaacttg cttatatttt attgaagtct cgacagctct
     5041 tcagaagtaa atttagaacg atgctgtcag ttcatattta tagatattag tgttttagca
     5101 gataaaacaa aatcaacaaa aattaagttc attttgtgat taaacctgca accatttttc
     5161 cattactttt tttctatagt taatggttat tgccatgatt tcttctgttt ggttctacta
     5221 agctagaaag ccagggtgaa gttaatgata attcccatta ttttatttct gtaccatgag
     5281 attgctgttg atgactgaaa taccaggtgc aaaaattaat gatttgattt ttgtacagtt
     5341 tcaatgagta ttttttactt attaaaaata aattaagaaa tgtaagaata tctttgtaaa
     5401 tcatgtttca taagttgact ccagagattc tgattttgct gtttattttg tgagtaatgt
     5461 tgctttggtg tttcctgatt ttcaagtttg caatcatgga gatacagcag ttattaggtg
     5521 tggaaggaca ttacctcaaa tgtcctcaga tggctccagg aaattctttt aaaacagttg
     5581 gagagaaata gtcgtgacca tgtaaaacct agaggatctg gtaaatccca tactactggt
     5641 tagggatttg taaagtccat ttctttttag agttcaaagc agttctgtta cttgtccata
     5701 agttcctcat aaattgtccc aaaggtagga catggaaata aatgtatatc tttatttttt
     5761 aatctactat gtcacactct ggtgatattc atggaacatt aaaaaagcaa ctatgtttat
     5821 tttataatta gtaaaatgaa gatagaaaat tgttcttttg aaatttttag ggaaaaaaaa
     5881 aatctcgtga cctaaatctt tccactataa tgaatattca ttgtgattgc aaatatctaa
     5941 ttttatataa tcactgtgta tggatttagc gattttactt ttcatagatt caaaaacata
     6001 taatctgaat gctttctctg aaaaaaaaaa aatcagagtt gagctcttga ggatcagagt
     6061 taagtatcca ttgataatat gtgttcattt tgctctatgt cataactttg tttttttatt
     6121 gagaaatata tatttttcaa aaacacatat atattcaaaa atacataaaa tataaatatg
     6181 cagttcaagg aataatttta aagcaactat ataactagca ctcagcttag tagaatatat
     6241 tgacagcagt tcagaaatta cacatgtagt tccttcccag tcacaaccag ctccctgcca
     6301 cgtacccttt ggtaattacc actatcctac cttgtatgat aattgtctct ttgtttttat
     6361 agtgttacca cctatgtgtg taaacttaaa caatacagtt tgcttgtttt tgagttttat
     6421 ttaaaatcat acattctttt gtagctgcat ttgttcaaga tgggattgat tcatgttggt
     6481 tgtagctgta ctttattctt cattatgtct gtgtaattta cttttctgtt aatatgccac
     6541 aatttattta ctgtagacaa ttgggatgtt tttagtttca ggcaattaca gtttcacaat
     6601 gaacatcatt ttatgtaact cctagtacaa agagtatata tttaggagta gaattttttg
     6661 gtcatagggt attcatatct taaattttat tagatgatta caaatttttt tctaagcatt
     6721 agtatgttgg ttggttttgt gttgctataa aggaatatcc aagactcggt aattcataaa
     6781 gaaaaaaggt ttatttggct catggttcag caggttgtac aaacattgca ccagcatccc
     6841 tgcaatcatg gcagaaggca aaggaggaac tggcgtatca catggctaga ggagcaagag
     6901 agaaatagag gaagtcccag atcattttta agaatcagat ctcacattaa ctcatggagc
     6961 aagaactcgt catctcaacg agggcaccaa gccatttatg agggatccag atatccatcc
     7021 ccataacccg aacacctccc accagccctc acctccaaca ctggggatca catttcaaca
     7081 tgatatttgc aggggacaaa tatccaaacc atatttctcc atatcttggt cagtgctggt
     7141 gttaacagtt tttgttttta attttgccaa tctggtggat gtgcaattgt atctcattga
     7201 agtgtcactc tgcatttctc tattacctgt gaagttgagt attttttcat aagtttattg
     7261 gccaatttga ctttctgttt ttgtaaagta tcttgtcagg actgccacac gtttttgttg
     7321 tgttgctaat ctttttcctc attgattcat aaaggatctt tataaatctt attctttgtt
     7381 ggctgtatag ttgccaatat cttctcccaa tttgtggctt gcctttccct cccttatgat
     7441 gttctttgat aaaaacaatt tattaatggt taagtactag gaagtatgag tgttttaaaa
     7501 ttagagcgtg agttgtttta aaaaaccatt ccctaccctg gagtcatgaa gatagtctta
     7561 tatatcgtct tcttaaagct ttagttttgc ctttcatatt taaatttttt tcatgaggaa
     7621 ttaatttggt gtatgctagg agatgcctca ctaccgttta ttgaaaaatc tgggttttat
     7681 tcctcctttc tatagtgcca ccaaagtcat gtattatacc cgtatgtgaa tacagatttc
     7741 atcaacatct gttgatgaaa agagtcaaac tctgtaaata ttttcagaga ttattctgag
     7801 ccaaatatga gtgaccatgg cctgtgaccc agccctcagg aggtccagag aacatgtgcc
     7861 ccaggtggtc agagtacatc ttggttttat atagaaggca tgagacatca aatacgttta
     7921 agaaatgcat tggtttggtt cagaaaggca ggacaactca aagcgggggc ttccagggta
     7981 taggttaatt taaaacattt tctggttgac aattggtcga gtttatctga agacctggga
     8041 tcaataggaa ggaaatattc aggttaaata agagattgtg gagaacaagt tttattgtgc
     8101 agaggaaact ctcagcagac ttcaaagaga gcaggttgta aagtgtttct tattggacct
     8161 aaaaggatgc ctgggtctta gttgattatc tcctggattt ggaaaggaag gaaggacaaa
     8221 aaaaaaatgg gtaaagggga aaggggattc tttatagaat gtagattttt cccacaaggg
     8281 atggctttgc agggccattt caagatatgg cagagaaaca tatttcgggg taaaatattt
     8341 tgattttctt tcttgttatg ccagagtcag attggaaagt taagtcacaa tatacagggt
     8401 taaataaaac ccatctgatg agaatttatg gtttgtagag catgactccc cagactcctt
     8461 agacaggaat ttgggcaaga taacaaaata tcagagctta gtccttacat ctctttctaa
     8521 acattttttc ccttttttct atccctgtgc tagtatacca tcatcatcat cattgtagct
     8581 gatatattct tgatatctgg ccaaacaaat cctcccaact tattgttctt ttagagtatc
     8641 ttggttattc tcagcccctt gtattttcag ttctcatatt tctaattgaa agcatgtaaa
     8701 tttgtcactc ctgcagtttc taattgtctt gctgaaattt tcaatttctt atctgcttca
     8761 aaatgaaaag cataattatt ttctagtctg tctaataatt ccagaatcaa aacccgcctg
     8821 tgggtctgtt tttattttgt ttgttctagt cttcattctt actgtcttgt ctccttgtgt
     8881 gcctggttac ctttaattat ttaccaatat tgtttgaaaa aactagaaat aacttgatgc
     8941 tcagaatgat atttttatcc tccacagagt tttttgcttc tggcaggtac ctgcattagt
     9001 aatttaggat tattttgatc cagtttcaga tactgaaatt ttccaggtca cctaggtgac
     9061 tgaaagctga gccacagact gtggtaatgc tcttctgttc atccttattt ctagggttca
     9121 accattcagg gtttcaaagc atggtttgga gttaccaggc ccttacctct tcactgaccc
     9181 tggactcttt ttgaatcttt agccccttag ctctatctac tcaacttccc agtggccttt
     9241 tgcaatctat aaatactcct aacacagtgg tcccaaatga atggttcatt tttctgaatt
     9301 tctatctttt ctcagatatt attggcatgg taattattca ccaacttatc agctccctgc
     9361 tgccttccta catctttgaa aagtatattt tatccagctt ttctaaatgt tttcaagtga
     9421 gaatgttaat ccaaattact tagcccacat tatttcctgt tgattatgtg taaaatacag
     9481 ttggtttatt tgtattgttt ttgtacctgg aaacaataaa ctctgtagtg attctctaaa
//
