LOCUS       NM_001161346           11228 bp    mRNA    linear   PRI 09-JUN-2024
DEFINITION  Homo sapiens checkpoint with forkhead and ring finger domains
            (CHFR), transcript variant 3, mRNA.
ACCESSION   NM_001161346
VERSION     NM_001161346.2
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 11228)
  AUTHORS   He,F., Ye,B., Wu,X., Pan,J., Wang,J. and Wang,X.
  TITLE     CHFR promotes metastasis of human gastric carcinoma by activating
            AKT and ERK via NRF2- ROS axis
  JOURNAL   BMC Gastroenterol 23 (1), 114 (2023)
   PUBMED   37024798
  REMARK    GeneRIF: CHFR promotes metastasis of human gastric carcinoma by
            activating AKT and ERK via NRF2- ROS axis.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 11228)
  AUTHORS   Hagiwara,T., Sugimoto,K., Momose,H., Irie,T., Honjo,K.,
            Okazawa,Y.U., Kawai,M., Kawano,S., Munakata,S., Takahashi,M.,
            Kojima,Y., Serizawa,N., Nagahara,A., Hoffman,R.M., Brock,M.V. and
            Sakamoto,K.
  TITLE     CHFR-Promoter-Methylation Status Is Predictive of Response to
            Irinotecan-based Systemic Chemotherapy in Advanced Colorectal
            Cancer
  JOURNAL   Anticancer Res 42 (2), 697-707 (2022)
   PUBMED   35093868
  REMARK    GeneRIF: CHFR-Promoter-Methylation Status Is Predictive of Response
            to Irinotecan-based Systemic Chemotherapy in Advanced Colorectal
            Cancer.
REFERENCE   3  (bases 1 to 11228)
  AUTHORS   Lu,Q., Li,Y., Lou,J., Li,P., Gu,Y. and Wang,X.
  TITLE     Circ-CHFR modulates the proliferation, migration, and invasion of
            ox-LDL-induced human aorta vascular smooth muscle cells through the
            miR-214-3p/PAPPA axis
  JOURNAL   Clin Hemorheol Microcirc 80 (4), 399-412 (2022)
   PUBMED   34842180
  REMARK    GeneRIF: Circ-CHFR modulates the proliferation, migration, and
            invasion of ox-LDL-induced human aorta vascular smooth muscle cells
            through the miR-214-3p/PAPPA axis.
REFERENCE   4  (bases 1 to 11228)
  AUTHORS   Wu,W., Zhao,J., Xiao,J., Wu,W., Xie,L., Xie,X., Yang,C., Yin,D. and
            Hu,K.
  TITLE     CHFR-mediated degradation of RNF126 confers sensitivity to PARP
            inhibitors in triple-negative breast cancer cells
  JOURNAL   Biochem Biophys Res Commun 573, 62-68 (2021)
   PUBMED   34388456
  REMARK    GeneRIF: CHFR-mediated degradation of RNF126 confers sensitivity to
            PARP inhibitors in triple-negative breast cancer cells.
REFERENCE   5  (bases 1 to 11228)
  AUTHORS   Luo,H., Zhou,Z., Huang,S., Ma,M., Zhao,M., Tang,L., Quan,Y.,
            Zeng,Y., Su,L., Kim,J. and Zhang,P.
  TITLE     CHFR regulates chemoresistance in triple-negative breast cancer
            through destabilizing ZEB1
  JOURNAL   Cell Death Dis 12 (9), 820 (2021)
   PUBMED   34462429
  REMARK    GeneRIF: CHFR regulates chemoresistance in triple-negative breast
            cancer through destabilizing ZEB1.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 11228)
  AUTHORS   Sanbhnani,S. and Yeong,F.M.
  TITLE     CHFR: a key checkpoint component implicated in a wide range of
            cancers
  JOURNAL   Cell Mol Life Sci 69 (10), 1669-1687 (2012)
   PUBMED   22159584
  REMARK    GeneRIF: CHFR is thought to contribute towards regulating mitotic
            entry and possible explanations for contradictory observations
            published on the functions and regulation of CHFR are presented.
            [review]
            Review article
REFERENCE   7  (bases 1 to 11228)
  AUTHORS   Mizuno,K., Osada,H., Konishi,H., Tatematsu,Y., Yatabe,Y.,
            Mitsudomi,T., Fujii,Y. and Takahashi,T.
  TITLE     Aberrant hypermethylation of the CHFR prophase checkpoint gene in
            human lung cancers
  JOURNAL   Oncogene 21 (15), 2328-2333 (2002)
   PUBMED   11948416
REFERENCE   8  (bases 1 to 11228)
  AUTHORS   Chaturvedi,P., Sudakin,V., Bobiak,M.L., Fisher,P.W., Mattern,M.R.,
            Jablonski,S.A., Hurle,M.R., Zhu,Y., Yen,T.J. and Zhou,B.B.
  TITLE     Chfr regulates a mitotic stress pathway through its RING-finger
            domain with ubiquitin ligase activity
  JOURNAL   Cancer Res 62 (6), 1797-1801 (2002)
   PUBMED   11912157
  REMARK    GeneRIF: Chfr regulates a mitotic stress pathway through its
            RING-finger domain with ubiquitin ligase activity.
REFERENCE   9  (bases 1 to 11228)
  AUTHORS   Kang,D., Chen,J., Wong,J. and Fang,G.
  TITLE     The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and
            inhibits Cdc2 at the G2 to M transition
  JOURNAL   J Cell Biol 156 (2), 249-259 (2002)
   PUBMED   11807090
  REMARK    GeneRIF: checkpoint protein Chfr is a ligase that ubiquitinates
            Plk1 and inhibits Cdc2 at the G2 to M transition
REFERENCE   10 (bases 1 to 11228)
  AUTHORS   Scolnick,D.M. and Halazonetis,T.D.
  TITLE     Chfr defines a mitotic stress checkpoint that delays entry into
            metaphase
  JOURNAL   Nature 406 (6794), 430-435 (2000)
   PUBMED   10935642
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC127070.10.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Aug 2, 2019 this sequence version replaced NM_001161346.1.
            
            Summary: This gene encodes an E3 ubiquitin-protein ligase required
            for the maintenance of the antephase checkpoint that regulates cell
            cycle entry into mitosis and, therefore, may play a key role in
            cell cycle progression and tumorigenesis. The encoded protein has
            an N-terminal forkhead-associated domain, a central RING-finger
            domain, and a cysteine-rich C-terminal region. Alternatively
            spliced transcript variants that encode different protein isoforms
            have been described. [provided by RefSeq, Mar 2014].
            
            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##
            Transcript exon combination :: AK027687.1, SRR11853561.7903.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000450056.7/ ENSP00000398735.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-59                AC127070.10        62213-62271
            60-204              AC127070.10        62478-62622
            205-304             AC127070.10        72164-72263
            305-414             AC127070.10        77424-77533
            415-474             AC127070.10        79035-79094
            475-654             AC127070.10        80020-80199
            655-822             AC127070.10        88184-88351
            823-982             AC127070.10        90591-90750
            983-1137            AC127070.10        92259-92413
            1138-1300           AC127070.10        93188-93350
            1301-1443           AC127070.10        96245-96387
            1444-1563           AC127070.10        98081-98200
            1564-1647           AC127070.10        101094-101177
            1648-1718           AC127070.10        101663-101733
            1719-1806           AC127070.10        102688-102775
            1807-1914           AC127070.10        105684-105791
            1915-1987           AC127070.10        106735-106807
            1988-11228          AC127070.10        108222-117462
FEATURES             Location/Qualifiers
     source          1..11228
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q24.33"
     gene            1..11228
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /note="checkpoint with forkhead and ring finger domains"
                     /db_xref="GeneID:55743"
                     /db_xref="HGNC:HGNC:20455"
                     /db_xref="MIM:605209"
     exon            1..59
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            60..204
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     CDS             72..2030
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /EC_number="2.3.2.27"
                     /note="isoform 3 is encoded by transcript variant 3; RING
                     finger protein 196; checkpoint with forkhead and ring
                     finger domains, E3 ubiquitin protein ligase; RING-type E3
                     ubiquitin transferase CHFR"
                     /codon_start=1
                     /product="E3 ubiquitin-protein ligase CHFR isoform 3"
                     /protein_id="NP_001154818.1"
                     /db_xref="CCDS:CCDS53848.1"
                     /db_xref="GeneID:55743"
                     /db_xref="HGNC:HGNC:20455"
                     /db_xref="MIM:605209"
                     /translation="MERPEEGKQSPPPQPWGRLLRLGAEEGEPHVLLRKREWTIGRRR
                     GCDLSFPSNKLVSGDHCRIVVDEKSGQVTLEDTSTSGTVINKLKVVKKQTCPLQTGDV
                     IYLVYRKNEPEHNVAYLYESLSEKQGMTQESFDTSGAGAGRGADPRVPPSSPATQVCF
                     EEPQPSTSTSDLFPTASASSTEPSPAGRERSSSCGSGGGGISPKGSGPSVASDEVSSF
                     ASALPDRKTASFSSLEPQDQEDLEPVKKKMRGDGDLDLNGQLLVAQPRRNAQTVHEDV
                     RAAAGKPDKMEETLTCIICQDLLHDCVSLQPCMHTFCAACYSGWMERSSLCPTCRCPV
                     ERICKNHILNNLVEAYLIQHPDKSRSEEDVQSMDARNKITQDMLQPKVRRSFSDEEGS
                     SEDLLELSDVDSESSDISQPYVVCRQCPEYRRQAAQPPHCPAPEGEPGAPQALGDAPS
                     TSVSLTTAVQDYVCPLQGSHALCTCCFQPMPDRRAEREQDPRVAPQQCAVCLQPFCHL
                     YWGCTRTGCYGCLAPFCELNLGDKCLDGVLNNNSYESDILKNYLATRGLTWKNMLTES
                     LVALQRGVFLLSDYRVTGDTVLCYCCGLRSFRELTYQYRQNIPASELPVAVTSRPDCY
                     WGRNCRTQVKAHHAMKFNHICEQTRFKN"
     exon            205..304
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            305..414
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            415..474
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            475..654
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            655..822
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            823..982
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            983..1137
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            1138..1300
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            1301..1443
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            1444..1563
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            1564..1647
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            1648..1718
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            1719..1806
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            1807..1914
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            1915..1987
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     exon            1988..11228
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3208..3213
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /note="hexamer: AATAAA"
     polyA_site      3233
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /note="major polyA site"
     regulatory      11143..11148
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
                     /note="hexamer: AATACA"
     polyA_site      11163
                     /gene="CHFR"
                     /gene_synonym="RNF116; RNF196"
ORIGIN      
        1 gcaatgtctc ttgacagcgg cggcggcgca gccggttccg ggttcggcgc ggggcgggga
       61 tgtgaatccc gatggagcgg cccgaggaag gcaagcagtc gccgccgccg cagccctggg
      121 gacggctcct gcgtctgggc gcggaggagg gcgagccgca cgtcctcctg aggaagcggg
      181 agtggaccat cgggcggaga cgaggttgcg acctttcctt ccccagcaat aaactggtct
      241 ctggagatca ctgtagaatt gtagtggatg aaaaatcagg tcaggtgaca ctggaagata
      301 ccagcaccag tggaacagtg attaacaagc tgaaggttgt taagaagcag acatgccctt
      361 tacagactgg ggatgtcatc tacttggtgt acaggaagaa tgaaccggaa cacaacgtgg
      421 catacctcta tgaatcttta agtgaaaagc aaggcatgac acaagaatcc tttgatacct
      481 caggtgcagg tgcagggcga ggggccgatc cccgggtccc tccgtcgtcg cccgccactc
      541 aggtgtgctt tgaggaacca cagccatcaa catcgacgtc agacctcttc cccacagcct
      601 cggcctcttc cacggagcct tctcctgcag ggcgagagcg ttcctccagt tgtgggtctg
      661 ggggtggtgg catctcccct aaaggaagtg gtccctctgt ggcaagtgat gaagtctcca
      721 gctttgcctc agctctccca gacagaaaga ctgcgtcctt ttcgtcgttg gaaccccagg
      781 atcaggagga tttggagccc gtgaagaaga aaatgagagg agatggggac cttgacctga
      841 acgggcagtt gttggtcgca caaccgcgta gaaatgccca aaccgtccac gaggacgtca
      901 gagcagcggc tgggaagcca gacaagatgg aggagacgct gacatgcatc atctgccagg
      961 acctgctgca cgactgcgtg agtttgcagc cctgcatgca cacgttctgc gcggcttgct
     1021 actcgggctg gatggagcgc tcgtccctgt gtcctacctg ccgctgtccc gtggagcgga
     1081 tctgtaaaaa ccacatcctc aacaacctcg tggaagcata cctcatccag catccagaca
     1141 agagtcgcag tgaagaagat gtgcaaagta tggatgccag aaataaaatc actcaagaca
     1201 tgctgcagcc caaagtcagg cggtcttttt ctgatgaaga agggagttca gaggacctgc
     1261 tggagctgtc agacgttgac agtgagtcct cagacattag ccagccatac gtcgtgtgcc
     1321 ggcagtgtcc tgagtacaga aggcaggcgg cgcagcctcc ccactgccca gcacccgagg
     1381 gcgagccagg agccccacag gccctggggg atgcaccctc cacgtccgtc agcctgacga
     1441 cagcagtcca ggattacgtg tgccctctgc aaggaagcca cgccctgtgc acctgctgct
     1501 tccagcccat gcccgaccgg agagcggagc gcgagcagga cccgcgtgtc gcccctcagc
     1561 agtgtgcggt ctgcctgcag cctttctgcc acctgtactg gggctgcacc cggaccggct
     1621 gctacggctg cctggccccg ttttgtgagc tcaacctggg tgacaagtgt ctggacggcg
     1681 tgctgaacaa caacagctac gagtcagaca tcctgaagaa ttacctggca accagaggtt
     1741 tgacatggaa aaacatgttg accgagagcc tcgtggctct ccagcgggga gtgtttctgc
     1801 tgtctgatta cagagtcacg ggagacaccg ttctgtgtta ctgctgtggc ctgcgcagct
     1861 tccgtgagct gacctatcag tatcggcaga acattcctgc ttccgagttg ccagtggccg
     1921 taacatcccg tcctgactgc tactggggcc gtaactgccg cactcaggtg aaagctcacc
     1981 acgccatgaa attcaatcat atctgtgaac agacaaggtt caaaaactaa gcatccagag
     2041 gccctgagca gctttcagca ctggaggtga agagagcgtg tttttaaaat acagagacaa
     2101 gcacgtcaag gtgttttcac agccccctga gggaagggac gcagggtctc cgacaggtgc
     2161 tctggggtga ctcttctgtg gagctttacc ctctgagtga gaccctcccc agagccccgg
     2221 gggccgcagc ccgccctcct ggtgagcgct gggcagggct cgtggtggca tcagcagcag
     2281 agacgaagcc tttctgtaac atgcggccgt cccgccgaga ggggcagttt tgctcttttg
     2341 tacattttcc gaaactacag ttaaagcaga agtctgtttt taggaaaagt ttcaagggag
     2401 aagggcaagt ttatcaaaaa cattgtttca ggagaaggga gcataagttt acagcctaca
     2461 ggacgtacac aatatcctgc tgctgggaaa accacagcat tttatctatt ttttatttta
     2521 ataggtttgg tgcttatctt ctaataagat ttaaatgtca caaactgtag cacaaataat
     2581 ataatttata atttacaaat tgactaaaat tgggtatagt atggtatttg aaagaataag
     2641 catatgcttc tgtttattaa aaaaagaaac cttccaatgt ccaaaactgc taaccctcga
     2701 cgtggccgcc aagttagtcg ctccttgcta accggtgagt gaccgcggcc ccgagcctgg
     2761 ggctggacgc aggtcccagg acatgctgct cccttgtgtg agtgaccgcg gccccgagcc
     2821 tggggctgga cgcaggtccc aggacgtgct gctcccttgt gtgagtgacc acggccccaa
     2881 gcccagggct ggaggcaggt cccaggacgc gccgctccct catgctgccc gggcccttcc
     2941 tccaagaccc tacagagcct gaggggcacc ttggcttccg cctgtgctag ctttgccatg
     3001 tcatctggaa taatacttga aattttgatt tttggaaaaa aaagtttttt atcttttgtt
     3061 gaaatcacct gttatccttg tttgtaaact gataactttt ttgcttcttc tcaggaatac
     3121 agttttcaac tgttgtcttg ctcttgatag aaactgagaa gcagcaatct gtatttgtgg
     3181 aggaaagtcc tctcttttgc atattctaat aaatgagccg cgtttgctcc tccgctctcg
     3241 tgttgggctc gtgtctgggg ctgcctcact tccccatgcg agggaggcag gccccatgca
     3301 gagtgagctc cgagtgcctc actgctagtg atggtcactc tgtcacctgc tgtccctcag
     3361 tgactcctgt gaaacctgct caggtctctt cattctgcca atgctgggaa gccacaacct
     3421 gttcatccag tgtggaggct ttgtcttcag ctgagcacca gaagaagcca caatgcagag
     3481 accctgagtt tgtgcaaggg tggggctgag aggggaggtc ccgtgttagt gcaggggtga
     3541 ggccgggagg ggaggtcccg agtttgtgta ggggcgaggc tgagcaggga ggttctgagt
     3601 tagtgcaggg gcgaggctga gcagggaggt cccgagttag tgcaggggcg aggctaaggg
     3661 ggaggtccca agtttgtgca ggggtgaggc tgagcaggga ggtcccaagt tagtgcaggg
     3721 gcgaggctga gaggggagat cccgagtttg tgcaggggcg aggctgagag gggaggtccc
     3781 tagttagtgc aggggtgagg ccgagaaggg aggtcccaag tttgtgcatg gatgaagcca
     3841 aaaggggagt ttgcacgttt gtgcaggggt gaggccaaga agggaagtct tgagttggtg
     3901 caggggtgag ggagagggga ggtcctgagt ttgtgcagag gcgaggctga gaggggaggt
     3961 ccctaagtgc aggggtgagg ccgagagggg aggttgcaaa tttgtgcagg ggtgaggcca
     4021 agaggggagg tcctgagtta gtgcgggggt gaggccgaga ggggaggtcc tgagtttgtg
     4081 cagaggcgag gctgagaggg gaggtcctta gtgcaggggt gaggctgaga gggggaggtc
     4141 ccaagtttgt gcaggggtga ggccgagggg aggttgcaag tttgtgcagg ggtgaggcca
     4201 agaggggagg tcctgagtta gtgcgggggt gaggccgaga ggggagttcc tgagtttgtg
     4261 cagaggcgag gctgagaggg gaggttgcca gtttgtgcag gtgcgaggct gagaggggag
     4321 gctggcattc gccaatgaag tgggctgggg ctaccctgcg tctgtgtctt agagagatcg
     4381 gttgatactc actcttcccc ttcccatctc caaaaagtag aaacaagaac acttgccctg
     4441 tagaggatgc tggtctttcc tcaggaccag ctgcacctgt ccaggaaggg caggcagctc
     4501 agagagcctc tgggctccag gtgtcctagg gactcactcc tgcttcctta gtccttcaga
     4561 gaagtccaac tcctggccca ctgtgaagag gatttctacc tggagcagtc ggaacagctt
     4621 gggtttggct gtgatgtgag ggaggaggcc ttgggagcag ggcagttatc ctcccagcgt
     4681 ggtaaggagc cgtgttttat ggaggcaggg agatcagggc agttactcct cgggtgtggt
     4741 aaggagctgt gttttatgga agcaggtggc cgtgaactca ttccgtcttt tcatgagctt
     4801 ctgtacttcc tcgtcctcaa gacccagcca tcccacccag caaaactgac cggctgtggt
     4861 ggttttggag ccctgctctc cttgtggggt ggctgcgtgg gtcgtccaca ggctttctgg
     4921 aggacagcct ggtgctgctg cagatcccac tgcttcttcc tggctccttg gcccagcctt
     4981 gggacaaacc cagggcaggg ctgcagctgc ccgctggccc cacagaccgt ctccccacgc
     5041 actcctcatc tgcggctccc tctgtgctcc ctggtgcccc tcagaagcgg gggtcagccc
     5101 tgcccacccc tccgtgtgct gcccaggctc caagccaggg aagggggcct caggttctag
     5161 gtgaacccgt ccaccccagt gaggcctctc tgggatggcc tctgtcatag cttctgactg
     5221 cagccaggaa gtctgggcag attggcttaa aacagactga gggattcagg ccaaccctcc
     5281 tccctaggcc agctacaaag gctgttttaa atctgcttta agtcatctta atgacctcag
     5341 ggccagcagg atgggagtgg tcgggcccag gtgtgagagc cggggtccag gggctgctcc
     5401 cagcaccaca cggccttcac cccaggggtg tggccaaggc agagaggcag ctgagtttgg
     5461 aaggggcttc cgccagcaag ggtttcctgg tgacagcccc ccagcttcgg gctggcaggc
     5521 tgggagagtg gagcaatgct ggccctgagg cagctgcagc cggctccctg aagaggcccc
     5581 agagtcactg ccagggccgc taggttgccg ggagccctgc actgggaagg gaaggaaagc
     5641 atgagaacgg aggggattta ggaaagtaga tcgtccctcc agcctggctt gatggggaaa
     5701 ccagaacgct gtccccgcgg ccgtgcccgc cctctgcctc cacgtgggct ccgttttggc
     5761 atgcacgcta gctcctgcgc cttctgaggg cggctgcagc cgtgtagaga agccgggtct
     5821 tgcctccctg aggacggagg gccgcatgca gagcacagcc tagccctgca gatccgcgcg
     5881 ctgaccagca gcaggacgga gccgggtgat cttcggggga gccacctcca gaaacgccta
     5941 gtgctggtaa ctggtagaca gccattattc aagcatcctc tacacttaga attgagttac
     6001 actgaaaaca aaggtgatga gtgctcagga cgcactactt tctagttagt ttaccgcacc
     6061 tgcctgttac ctgcaggccc gagggtgtgt gcttctgtgg cctgtgtggg atggcacccc
     6121 ttccagcctt acccactcag ctcagttggc ctggttggaa tgggccctgg gaggagtgtt
     6181 tgcactgtgg aaattggtaa atgcttcaaa tcagggtggt ttttaatttt gcttttgttt
     6241 tcttctgaag agaaggttgt taaacaccag cacagtgctg caccaggcag ccagcatata
     6301 atcatgagaa ataagtagtt gtttaagcca ctgcatttgg ggtggtttat tacatagtaa
     6361 tgataaccat atcatggccc ttgaaggccc agcatgtatg acccctgcct ccacccctca
     6421 gaaaacctct tctccctacc tgcttctcct ggagcccctc aggtgttcct ctgcttctcc
     6481 accgaaccag ctaattctca caaacagccc ctcaggtacc agcccctccc tctgcagcct
     6541 ctcctcattc agctcctgca gggctgcccc caccccgcca gccagtctag tttcccccca
     6601 gcacctgtca ctatcggaaa ggaaacatct gtttaccgtt tgtctccccc tctcaaaaaa
     6661 atagagcagg gatcttgcct gtctgcccac tgttgtttat ttgtctgaaa tgtttggccc
     6721 cagggcagca tctactgatc actgaccagt tggctactga acggtgaagg tctgatgagc
     6781 tgatgagccg tcccctgggc ttgaaatctt tcccgcggca caaacaggcg ccccttcctc
     6841 tgtcgctcac ttttcacggt tgtctccttc tgaggcggtg agtctagatg gtggggtctt
     6901 aaagttcctc acacagagca gacacttggt cgtgcatgtc tgtggaagga atggactcag
     6961 gagagaatgt tgaaggccag tcagaccagg agtgagtgcc gtgcgccgtg ctgggagcct
     7021 gtcactgtga gtgccgtgcg ccgtgctggg agcctgtcac tgtgagtgcc gtgcgccgtg
     7081 ctgggagcct gtcactgtga gtgccgtgcg ccctgctggg agcctgtcac tgtgagtgcc
     7141 gtgcgccgtg ctgggagcct gtcactgtga gggccgagcg ccgtgctggg agcctgtcac
     7201 tgtgagggcc gtgcgccgtg ctgggagcct gtcactgtga gggccgtgcg ccgtgctggg
     7261 agcctgtcac tgtgagggcc gtgcgccgtg ctgggagcct ggcactgtga gtgccgtgcg
     7321 ccgtgctggg agcctggcac tgtgagggcc gtgcgccgtg ctgggagcct ggcactgtga
     7381 gtgccgtgcg ccgtgctggg agcctgtcac tgtgagtgcc gtgcgccgtg ctgggagcct
     7441 gtcactgtga gtgccgtgcg ccgtgctggg agcctggcac tgtgagtgcc gtgcgccgtg
     7501 ctgggagcct ggcactgtga gtgccgtgcg ccgtgctggg agcctggcac tgtgagtgcc
     7561 gtgcgccgtg ctgggagcct ggcactctga gtgccgtgcg ccgtgctggg agcctgtcac
     7621 tgtgagtgcc gtgcgccgtg ctgggagcct gtcactgtga gtgccgtgcg ccgtgctggg
     7681 agcctggcac tgtgagtgcc gtgcgccgtg ctgggagcct atcactgtga gggccgtgcg
     7741 ctgtgctggg agcctggcac tgtgagggcc gtgcgctgtg ctgggagcat gcatttgtga
     7801 gacccgccct gcccagtgct ggccttgaat gtgggtccac ttgggccgct ggatcaaaac
     7861 gccgcagaac aggcggctta aacaacagaa agtattttct cacagttctg gggcctggaa
     7921 ctctgagatc agggtgtcag cggggccggt tcctctttgg tctgtctcct tggctcgtgg
     7981 gcagcatctc cttgagttct cacgtcatct tctcttcatg cgtgtttgtg ccctaatctc
     8041 ttcctgcgag gacaccagtc ctattggatt agggcccaca ccagtggcct cattttatct
     8101 taatcacctc tttaaagacc acacctacta aaactggaac gatatagaga agattagcat
     8161 ggcccacgtg caggcatgac acccaaattc atgacgtgtt ccatgtctgc agatacagtc
     8221 acctctgagg tcctgggatt tagggcttga acatattgta acactctgcc atcaaagctc
     8281 gcacgccacg gggttttata aaaattgggt ggttttgttt gttgttgttt ggcaaacccc
     8341 acatgctgga taccattgac actccgtggt gggctgagcc atgtccccgt cccgccacca
     8401 cagatacccg tatccgatca cttgagcctg tgatgatgtt gccttgcacc gtaaaagggg
     8461 ctttgcagat atggtggaat taaggacctt gagatgaggg gaggatcctg gattagcttg
     8521 tgggccctct gtgcaacagt aggagtcgtt gtaagaggga agcaagaggc cgggcgtggt
     8581 ggctcacgcc tgtactccca gcactttggg aggctgaggc gggcggatca cgaggtcagg
     8641 agatcgagac catcctggct aacatggtga aaccccgtct ctactaaaaa ataccaaaaa
     8701 attagccggg cgtggtggtg ggtgcctgta gtcccagcta ctcgggaggc tgaggcagga
     8761 gaatggcttg aacccgggag gcggagcttg cagtgaaccg agatcgcacc actgcactcc
     8821 cgcctgggcg acagagcgag actctatctc aaaaaaaaaa aaaaaaaaaa agcaagcaag
     8881 aagtcaaagg caggaagagg aggcttggtg acagagaaga ggtgggaggg atgtgctttg
     8941 cagagggagc aagggcctcc agccaggaga ggagggcagg ctgtcgaagc agaaaagaaa
     9001 acagatctcc ctgcagggcc accagaagga accagccctg cctgcccctt cattttggac
     9061 ttccgagctc cagaactgca agagaataaa tctagtttaa gcagcaaagt tggtggtaac
     9121 ttcttagagc agccacagga agctcactac cccccacaca ctcatcccgt ttggtttttg
     9181 ttttcaggaa gggtccagtc tgtctcagag gtgctgtggt tggaggtgga gtgtggggca
     9241 tggctgagca cccaacatcc gcttcaccct ctcccctgct ccccagcacg ttccttcacc
     9301 ctgtagctct aggtctctgt ggcagacact cagctctaac tgctgacctg atggctccac
     9361 ttggtgttca aacatcccag attcatgttg tcaaagagag ctgtttccag tggggacccc
     9421 aggcccacca cgtacgcccg gcagacctgc cctctccact gtcagaagat ggcatggcct
     9481 ccctgtagct caggcccaac cccaggagtc atcctgctgg ctgtcctcag tgccccaggc
     9541 ttctcttcag gggcttcttg tggctctgat tgttgccccc tcacctcact gctcttctcc
     9601 cagatctgtg cgtgcattgg tcctccttgt cacgcacgtt cagctcaaat attacttcct
     9661 caaaggtgcc tttgagtact cgttctcctt gcctttccct ctcctgggac actgttccca
     9721 ccagtacctg catgattcct tttttttctt ttccttttct ttttttgttt ttgagacagt
     9781 gtcttgctct gttgtcaggg ctggagggca gtggcgcaat gtcagctcac tgcagcctcc
     9841 acctcctggg ctcagatgat cctcccacct cagcctcctg agtagctggg actacaggtg
     9901 cacaccacca cacccagcta atttttagta gagagcaggg tttcaccatg ttgcccaggc
     9961 tggtcttgaa ctcctgagtt caagcgatct gcccgcctct acctcccaca gtgctgggat
    10021 tccaggcgta agccgccacg cccagcaact ccgtttctta cttgttggct cacattctcc
    10081 tgagaagtcc tccctcaacc atcggcctga aatagcagcg agcctcccca gggttgcctc
    10141 tgccttttct tgactctttc tgtcaccttc tatgcttgtt gtctggtccc cactagaata
    10201 taccttctgt aagagcaggg atttgggaca gtgcctagaa tagtacttgc agacagtagg
    10261 ctacgataaa tatgaatgac ggccccatgc agatggtagc ccctctcgct cgaacgcttc
    10321 acccagtttt attttctttt catcagttac cgccctctga aggtatccac acacaaacat
    10381 gaaactggac caaagcaggg accccccgca cgcagaatag tgctgggctc gcgtaaggca
    10441 cctcagtggg tccatcagct gatgcatgga cagacaaaat gggtgtatcc agacactgga
    10501 gtatcgtgca gcgaggaaac gtgctgagtg tggatggacc ttaaacacac catgcaagtg
    10561 aaaaggcgtc acagaaggcc acatacgata tgatcccatt tctatgaaat gtccagaaga
    10621 ggcacattca taaagacaga aggtgactga gtggttgtcg ggctgggtgg aggggatagg
    10681 gagtgaatgc aagaaggatc cttctgaggt aacggaagta tccggaaact gggttggagt
    10741 gatgggtgca cagctctgca catttactac agtcgctgaa ctgcacacac aacacgggta
    10801 tattttattg catagaaatt gtattaaagc tgttaagaat tttacttaga ttagcatttt
    10861 tcccacactg tgccatcaac ttagtatatg attagattca ttgtttctaa ctgtatttaa
    10921 atttaatgtt tgtcacattt tgcttgctaa atttttaaaa ttttaaatta ctgtgggtac
    10981 ataaaaggtg tatatattta tggagtacct tgatatttta atacagacat acaatgtata
    11041 atgatcaact cccagtaact ggggtatcca tcacctcaag cctgtatcat ttctttgtta
    11101 ggaacattcc agttccactc tttttgttat ttaaaaatat acaatacatt attattaact
    11161 atattcaccc tcctgtgcta tggaatacta gatcttatgc taattaaatg ttttccctat
    11221 ttctccca
//
