LOCUS       NM_005188              11168 bp    mRNA    linear   PRI 08-FEB-2025
DEFINITION  Homo sapiens Cbl proto-oncogene (CBL), mRNA.
ACCESSION   NM_005188
VERSION     NM_005188.4
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 11168)
  AUTHORS   Li,X., Sun,W., Huang,M., Gong,L., Zhang,X., Zhong,L., Calderon,V.,
            Bian,Z., He,Y., Suh,W.K., Li,Y., Song,T., Zou,Y., Lian,Z.X. and
            Gu,H.
  TITLE     Deficiency of CBL and CBLB ubiquitin ligases leads to hyper T
            follicular helper cell responses and lupus by reducing BCL6
            degradation
  JOURNAL   Immunity 57 (7), 1603-1617 (2024)
   PUBMED   38761804
  REMARK    GeneRIF: Deficiency of CBL and CBLB ubiquitin ligases leads to
            hyper T follicular helper cell responses and lupus by reducing BCL6
            degradation.
REFERENCE   2  (bases 1 to 11168)
  AUTHORS   Liu,L., Zhu,Y., Lan,J., Chu,L., Li,W. and Xue,C.
  TITLE     Association between CBL gene polymorphism and susceptibility of
            microscopic polyangiitis in a Chinese population: A case-control
            analysis
  JOURNAL   Cytokine 179, 156596 (2024)
   PUBMED   38669907
  REMARK    GeneRIF: Association between CBL gene polymorphism and
            susceptibility of microscopic polyangiitis in a Chinese population:
            A case-control analysis.
REFERENCE   3  (bases 1 to 11168)
  AUTHORS   Su,Y., Meng,L., Ge,C., Liu,Y., Zhang,C., Yang,Y., Tian,W. and
            Tian,H.
  TITLE     PSMD9 promotes the malignant progression of hepatocellular
            carcinoma by interacting with c-Cbl to activate EGFR signaling and
            recycling
  JOURNAL   J Exp Clin Cancer Res 43 (1), 142 (2024)
   PUBMED   38745188
  REMARK    GeneRIF: PSMD9 promotes the malignant progression of hepatocellular
            carcinoma by interacting with c-Cbl to activate EGFR signaling and
            recycling.
            Erratum:[J Exp Clin Cancer Res. 2024 Oct 18;43(1):287. doi:
            10.1186/s13046-024-03209-2.. PMID: 39420369]
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 11168)
  AUTHORS   Zhang,S., Jia,X., Dai,H., Zhu,X., Song,W., Bian,S., Wu,H., Chen,S.,
            Tang,Y., Chen,J., Jin,C., Zhou,M., Xie,H., Zheng,S. and Song,P.
  TITLE     SERPINE2 promotes liver cancer metastasis by inhibiting
            c-Cbl-mediated EGFR ubiquitination and degradation
  JOURNAL   Cancer Commun (Lond) 44 (3), 384-407 (2024)
   PUBMED   38407942
  REMARK    GeneRIF: SERPINE2 promotes liver cancer metastasis by inhibiting
            c-Cbl-mediated EGFR ubiquitination and degradation.
REFERENCE   5  (bases 1 to 11168)
  AUTHORS   Joazeiro,C.A., Wing,S.S., Huang,H., Leverson,J.D., Hunter,T. and
            Liu,Y.C.
  TITLE     The tyrosine kinase negative regulator c-Cbl as a RING-type,
            E2-dependent ubiquitin-protein ligase
  JOURNAL   Science 286 (5438), 309-312 (1999)
   PUBMED   10514377
REFERENCE   6  (bases 1 to 11168)
  AUTHORS   Jones,C., Penny,L., Mattina,T., Yu,S., Baker,E., Voullaire,L.,
            Langdon,W.Y., Sutherland,G.R., Richards,R.I. and Tunnacliffe,A.
  TITLE     Association of a chromosome deletion syndrome with a fragile site
            within the proto-oncogene CBL2
  JOURNAL   Nature 376 (6536), 145-149 (1995)
   PUBMED   7603564
REFERENCE   7  (bases 1 to 11168)
  AUTHORS   Rivero-Lezcano,O.M., Sameshima,J.H., Marcilla,A. and Robbins,K.C.
  TITLE     Physical association between Src homology 3 elements and the
            protein product of the c-cbl proto-oncogene
  JOURNAL   J Biol Chem 269 (26), 17363-17366 (1994)
   PUBMED   7517397
REFERENCE   8  (bases 1 to 11168)
  AUTHORS   Blake,T.J. and Langdon,W.Y.
  TITLE     A rearrangement of the c-cbl proto-oncogene in HUT78 T-lymphoma
            cells results in a truncated protein
  JOURNAL   Oncogene 7 (4), 757-762 (1992)
   PUBMED   1565471
REFERENCE   9  (bases 1 to 11168)
  AUTHORS   Blake,T.J., Shapiro,M., Morse,H.C. 3rd and Langdon,W.Y.
  TITLE     The sequences of the human and mouse c-cbl proto-oncogenes show
            v-cbl was generated by a large truncation encompassing a
            proline-rich domain and a leucine zipper-like motif
  JOURNAL   Oncogene 6 (4), 653-657 (1991)
   PUBMED   2030914
REFERENCE   10 (bases 1 to 11168)
  AUTHORS   Savage,P.D., Shapiro,M., Langdon,W.Y., Geurts van Kessel,A.D.,
            Seuanez,H.N., Akao,Y., Croce,C., Morse,H.C. 3rd and Kersey,J.H.
  TITLE     Relationship of the human protooncogene CBL2 on 11q23 to the
            t(4;11), t(11;22), and t(11;14) breakpoints
  JOURNAL   Cytogenet Cell Genet 56 (2), 112-115 (1991)
   PUBMED   2013228
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB457271.2, BC132733.1,
            AP002956.1 and AA806454.1.
            
            On Aug 31, 2019 this sequence version replaced NM_005188.3.
            
            Summary: This gene is a proto-oncogene that encodes a RING finger
            E3 ubiquitin ligase. The encoded protein is one of the enzymes
            required for targeting substrates for degradation by the
            proteasome. This protein mediates the transfer of ubiquitin from
            ubiquitin conjugating enzymes (E2) to specific substrates. This
            protein also contains an N-terminal phosphotyrosine binding domain
            that allows it to interact with numerous tyrosine-phosphorylated
            substrates and target them for proteasome degradation. As such it
            functions as a negative regulator of many signal transduction
            pathways. This gene has been found to be mutated or translocated in
            many cancers including acute myeloid leukaemia, and expansion of
            CGG repeats in the 5' UTR has been associated with Jacobsen
            syndrome. Mutations in this gene are also the cause of Noonan
            syndrome-like disorder. [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 :: BC132733.1, SRR14038193.522698.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000264033.6/ ENSP00000264033.3
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-8                 DB457271.2         64-71
            9-5718              BC132733.1         1-5710
            5719-10935          AP002956.1         171971-177187
            10936-11168         AA806454.1         11-243              c
FEATURES             Location/Qualifiers
     source          1..11168
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q23.3"
     gene            1..11168
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /note="Cbl proto-oncogene"
                     /db_xref="GeneID:867"
                     /db_xref="HGNC:HGNC:1541"
                     /db_xref="MIM:165360"
     exon            1..274
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     CDS             80..2800
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /EC_number="2.3.2.27"
                     /note="oncogene CBL2; proto-oncogene c-Cbl; RING finger
                     protein 55; signal transduction protein CBL; casitas
                     B-lineage lymphoma proto-oncogene; Cas-Br-M (murine)
                     ecotropic retroviral transforming sequence; fragile site,
                     folic acid type, rare, fra(11)(q23.3); Cbl proto-oncogene,
                     E3 ubiquitin protein ligase; RING-type E3 ubiquitin
                     transferase CBL"
                     /codon_start=1
                     /product="E3 ubiquitin-protein ligase CBL"
                     /protein_id="NP_005179.2"
                     /db_xref="CCDS:CCDS8418.1"
                     /db_xref="GeneID:867"
                     /db_xref="HGNC:HGNC:1541"
                     /db_xref="MIM:165360"
                     /translation="MAGNVKKSSGAGGGSGSGGSGSGGLIGLMKDAFQPHHHHHHHLS
                     PHPPGTVDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTILSRY
                     EGKMETLGENEYFRVFMENLMKKTKQTISLFKEGKERMYEENSQPRRNLTKLSLIFSH
                     MLAELKGIFPSGLFQGDTFRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSG
                     LEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNWNSLAVTHPGYMAFLTYDE
                     VKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFRE
                     GFYLFPDGRNQNPDLTGLCEPTPQDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVK
                     IEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPFDPRGSGSLLRQGAEGA
                     PSPNYDDDDDERADDTLFMMKELAGAKVERPPSPFSMAPQASLPPVPPRLDLLPQRVC
                     VPSSASALGTASKAASGSLHKDKPLPVPPTLRDLPPPPPPDRPYSVGAESRPQRRPLP
                     CTPGDCPSRDKLPPVPSSRLGDSWLPRPIPKVPVSAPSSSDPWTGRELTNRHSLPFSL
                     PSQMEPRPDVPRLGSTFSLDTSMSMNSSPLVGPECDHPKIKPSSSANAIYSLAARPLP
                     VPKLPPGEQCEGEEDTEYMTPSSRPLRPLDTSQSSRACDCDQQIDSCTYEAMYNIQSQ
                     APSITESSTFGEGNLAAAHANTGPEESENEDDGYDVPKPPVPAVLARRTLSDISNASS
                     SFGWLSLDGDPTTNVTEGSQVPERPPKPFPRRINSERKAGSCQQGSGPAASAATASPQ
                     LSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREFVSISSPAHVAT"
     exon            275..522
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            523..669
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            670..826
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            827..948
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            949..1086
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            1087..1174
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            1175..1306
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            1307..1510
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            1511..1642
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            1643..2020
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            2021..2115
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            2116..2232
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            2233..2330
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            2331..2513
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     exon            2514..11168
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /inference="alignment:Splign:2.1.0"
     regulatory      11143..11148
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /note="hexamer: AATAAA"
     polyA_site      11168
                     /gene="CBL"
                     /gene_synonym="C-CBL; CBL2; FRA11B; NSLL; RNF55"
                     /note="major polyA site"
ORIGIN      
        1 cttcacgccc tgcttctctc cctcgctcgc agtcgagccg agccggcgga cccgcctggg
       61 ctccgaccct gcccaggcca tggccggcaa cgtgaagaag agctctgggg ccgggggcgg
      121 cagcggctcc gggggctcgg gttcgggtgg cctgattggg ctcatgaagg acgccttcca
      181 gccgcaccac caccaccacc accacctcag cccccacccg ccggggacgg tggacaagaa
      241 gatggtggag aagtgctgga agctcatgga caaggtggtg cggttgtgtc agaacccaaa
      301 gctggcgcta aagaatagcc caccttatat cttagacctg ctaccagata cctaccagca
      361 tctccgtact atcttgtcaa gatatgaggg gaagatggag acacttggag aaaatgagta
      421 ttttagggtg tttatggaga atttgatgaa gaaaactaag caaaccataa gcctcttcaa
      481 ggagggaaaa gaaagaatgt atgaggagaa ttctcagcct aggcgaaacc taaccaaact
      541 gtccctcatc ttcagccaca tgctggcaga actaaaagga atctttccaa gtggactctt
      601 tcagggagac acatttcgga ttactaaagc agatgctgcg gaattttgga gaaaagcttt
      661 tggggaaaag acaatagtcc cttggaagag ctttcgacag gctctacatg aagtgcatcc
      721 catcagttct gggctggagg ccatggctct gaaatccact attgatctga cctgcaatga
      781 ttatatttcg gtttttgaat ttgacatctt tacccgactc tttcagccct ggtcctcttt
      841 gctcaggaat tggaacagcc ttgctgtaac tcatcctggc tacatggctt ttttgacgta
      901 tgacgaagtg aaagctcggc tccagaaatt cattcacaaa cctggcagtt atatcttccg
      961 gctgagctgt actcgtctgg gtcagtgggc tattgggtat gttactgctg atgggaacat
     1021 tctccagaca atccctcaca ataaacctct cttccaagca ctgattgatg gcttcaggga
     1081 aggcttctat ttgtttcctg atggacgaaa tcagaatcct gatctgactg gcttatgtga
     1141 accaactccc caagaccata tcaaagtgac ccaggaacaa tatgaattat actgtgagat
     1201 gggctccaca ttccaactat gtaaaatatg tgctgaaaat gataaggatg taaagattga
     1261 gccctgtgga cacctcatgt gcacatcctg tcttacatcc tggcaggaat cagaaggtca
     1321 gggctgtcct ttctgccgat gtgaaattaa aggtactgaa cccatcgtgg tagatccgtt
     1381 tgatcctaga gggagtggca gcctgttgag gcaaggagca gagggagctc cctccccaaa
     1441 ttatgatgat gatgatgatg aacgagctga tgatactctc ttcatgatga aggaattggc
     1501 tggtgccaag gtggaacggc cgccttctcc attctccatg gccccacaag cttcccttcc
     1561 cccggtgcca ccacgacttg accttctgcc gcagcgagta tgtgttccct caagtgcttc
     1621 tgctcttgga actgcttcta aggctgcttc tggctccctt cataaagaca aaccattgcc
     1681 agtacctccc acacttcgag atcttccacc accaccgcct ccagaccggc catattctgt
     1741 tggagcagaa tcccgacctc aaagacgccc cttgccttgt acaccaggcg actgtccctc
     1801 cagagacaaa ctgccccctg tcccctctag ccgccttgga gactcatggc tgccccggcc
     1861 aatccccaaa gtaccagtat ctgccccaag ttccagtgat ccctggacag gaagagaatt
     1921 aaccaaccgg cactcacttc cattttcatt gccctcacaa atggagccca gaccagatgt
     1981 gcctaggctc ggaagcacgt tcagtctgga tacctccatg agtatgaata gcagcccatt
     2041 agtaggtcca gagtgtgacc accccaaaat caaaccttcc tcatctgcca atgccattta
     2101 ttctctggct gccagacctc ttcctgtgcc aaaactgcca cctggggagc aatgtgaggg
     2161 tgaagaggac acagagtaca tgactccctc ttccaggcct ctacggcctt tggatacatc
     2221 ccagagttca cgagcatgtg attgcgacca gcagattgat agctgtacgt atgaagcaat
     2281 gtataatatt cagtcccagg cgccatctat caccgagagc agcacctttg gtgaagggaa
     2341 tttggccgca gcccatgcca acactggtcc cgaggagtca gaaaatgagg atgatgggta
     2401 tgatgtccca aagccacctg tgccggccgt gctggcccgc cgaactctct cagatatctc
     2461 taatgccagc tcctcctttg gctggttgtc tctggatggt gatcctacaa caaatgtcac
     2521 tgaaggttcc caagttcccg agaggcctcc aaaaccattc ccgcggagaa tcaactctga
     2581 acggaaagct ggcagctgtc agcaaggtag tggtcctgcc gcctctgctg ccaccgcctc
     2641 acctcagctc tccagtgaga tcgagaacct catgagtcag gggtactcct accaggacat
     2701 ccagaaagct ttggtcattg cccagaacaa catcgagatg gccaaaaaca tcctccggga
     2761 atttgtttcc atttcttctc ctgcccatgt agctacctag cacaccatct ccctgctgca
     2821 ggtttagagg accagtgagt tgggagttat tactcaagtg gcacctagaa gggcaggagt
     2881 tcctttggtg acttcacagt gaagtcttgc cctctctgtg ggatatcaca tcagtggttc
     2941 caagatttca aagtggtgaa atgaaaatgg agcagctagt atgttttatt attttatggg
     3001 tcttgagtgc atttgaaggt gtccttcagt tcccacgtag agagagtgtg gattatatta
     3061 catgataacc tacctgggga acagtccaga aagctataga acaagtattt tgctggaaat
     3121 cctaattgag gacttaagac ttcctgggtt aaggatgtgg ccgtgtgtgt gtgtgtctgc
     3181 ctgtggttgt atgtgtcctt gtgattataa gattaacctg ctgtgtgtgt taattccagg
     3241 cagggaatta gcacaaaagg tttaggaagg aatctttttt taaagacttc catctactgt
     3301 ggtattatac ccaagcctag tgtgtattac aacttcaaca ctcccctttg gcttatatta
     3361 ccatgtgcat agctaaagtc ttctattttt agaacacctt ctgtctgttc tttccccatc
     3421 aactccttcc tcatccttct tggtgttctg tcatgggcca tgggcttgct atggccagcc
     3481 ttactgaggc caagcagctt atgggatgtt ctttattgtg tgtgatggta ttggtttgtt
     3541 tggtagataa gtgggaggaa aagtactgtt gctacactat tataggcatg tttgatacta
     3601 gcagctaaca ctggtcactc caaagcactg tttctatagg aacattgaag ctattaagat
     3661 gttttgatta tcctaattac ataatgaccg atttgagata gaggccttta aatacattcc
     3721 atgccctccc cagaaaatag tctgtgggag tcagttgcct tggtgccagg tatgtgttct
     3781 gatgtaggtc atgagtcttt ctacttaatg ggaagggaag aacatttgtt tccaggatga
     3841 ctttctggcc agaataccgg aaagctttta ggaagcttcg ttcacatgct atttaaatgc
     3901 acaaaataga cagtaaggat ttatctgttc agtttttctt cccagtgaat taatttcagc
     3961 ttatatgggt gtcttcattt gaacatgagg aatattaggt tatattttca gcagtggttt
     4021 tttcctttgc cctttaagga gtggggataa tgtccacggt ggcccagcct cttgctgatg
     4081 gcaccttccc tgcattgctg cctcccgatg atgtggttct tttcttgtgc ctgtggcttt
     4141 gggaatgtaa catctctttc ctcctttcct tcccttttcc tcttcacctg aggtcctaaa
     4201 tactctctgt aattactgtg ttcttcacgg taattagaca tcattcagtg aataaattac
     4261 tgtagtcaaa gacagtatgg gctggcagtt tgtgtaattg caagttcata aagagaattg
     4321 agggtccagt tgggagaact attagtcagt tcttttatat gctgataaat gatccctcga
     4381 gttcagttag tattctgtcc agagtgttta gctcactttc ttagcagtgt gtaagctttc
     4441 tccatgtcag aagcaagcct gctctttgat aaatctgtct tcctgaaaat ctaaatcatg
     4501 cttttgtctt tagatctaca cagaaatgac cctccttgga tcagttttct ttccagtcta
     4561 atcatctttg gaactaaaac ttgttctaac tcgtctcttg gcattcagct actcctagat
     4621 cttttggttt tatcccctgg cctcagagcc atttatattc ccagagtagg cagtacagga
     4681 tctcgtgttg atttgctgtg gttacccagt gtcttctcta catggcataa agcggcaaag
     4741 cccaccatta ggtgaggcgg tcccgagttg aggtagagtg gggcagagga agatggcagt
     4801 gaatatcaaa cagtagaccg ccatcaactt ctaacagcca gtacacacac tgtttcattt
     4861 tgaggtaacg ttcagttttg cattttgttt aaatattgaa ggcctagaca aagaactaga
     4921 aaaaaaaaag cagtttccag gcccatccat attgtaattt ttctttatct gcagatattg
     4981 cctgtagtct aaagatctct ttggaagaca aagcattggc tatatatctt ttgccttttc
     5041 catgcatcta aatcttctct ggagattatc tccctactgt gtaggttaag ggcagtctcg
     5101 acttttcctt ttttgagtcc tgtgtggctc tttgaatcag cgtgaaactg aggctccagc
     5161 tccctgtgtt gtgtgtgtgt gccatccatg ggcttgggtg tcagtttgtc acaggtatct
     5221 gccagcattc aaggttttgg atcatttcat gaggatcttt cctttgactg ggtgctgtga
     5281 ggacacacct gggtctgtgc ctgagattgc caggcaagat taaggaaagt tttcatgtgg
     5341 cttttgtttt gaggttattc tcaaaacctt aatttcttat attttctgtt gactaaggca
     5401 ccagtaaccc attcttcacc ctccatttgt atggcaattt aaaagtcttt ggctttgctc
     5461 tgaatttaat taaaactgcc ttttatgaac agacttcgag ttttgccatt ttgggcaagc
     5521 ccttccgctt gtcccttcct agtggctaat aaagtaaaaa aacccacact actttgttct
     5581 ctttttctca tattcattgg gctgttgtat tcagccagtc tcatgctttc cctgggtctt
     5641 cacggattgc tttccaagct gccttgttgc ggggttgctg cagagcagca actggacctt
     5701 tccagctgtc gccatgttcc ttccactaaa gtagagggtt cttaaaatgg aaaaacctgt
     5761 gggctcttca tatacctccc tttagttaag taatagacca ggcagcttct catctcagca
     5821 tttacctgtt aatatttttg tgaatagtgc tctctacctg tgggtggccg ttctcttcca
     5881 cttgctcgtc tccccccagc cccattctgc ataatctacc attcttctcc tctctttctc
     5941 ttcttataca gaccctcatt actggggccc aagatgtggg atactactgt tagtattatt
     6001 taactatttt gtagatttaa aagatttctg gttaagggag gtgggggtca ctgttcatca
     6061 ctcttaaaat atgtgttttc tctatagaaa agtaaaatgt gtttatggtc ccaaacagtc
     6121 aactcacaaa tttttataac aaaatttcct tgtaaaaact agggaccatc tatatattcc
     6181 ctttaagatc tagttctttt tgtaggtgtt cagcaatggt gataaagcag aatattctcc
     6241 tacctcacgt cattaaagtc agaagattat agaccttctc aaactataag tccctcttct
     6301 tgccgttggc ctttctgact ctggaatgac cactgttcat tgaaaaatag ttttctgact
     6361 attggtctgg ctctaacagt ttgtttgttc atccagcaaa tgtttatgag tgatgaccat
     6421 gtgccagaaa tgtcaggtat gtgtccttcc cttggcgcca catagtagtt tactaatgtt
     6481 tgggggattg tacttggact gtcatagcct ctgcgtttga ccttaaaata gctcttccca
     6541 gtaagattgt gcaattttta ttcacagctc ttccatgtag acttaccttt cctcatagag
     6601 ctatcctggt taataacagg ccaagattct cccattatcc cctgttgtct cctgtagctt
     6661 tgataatgcc tgggagattc cttggtgtaa gtgtcatgga taccgactgt ttttatgttg
     6721 gaatttgttc caacataatt agaatctgtt tggtgagttg aaaggtaagt tggctcagag
     6781 ttgcacagta gggcattaaa tgtttaagca aagcatctgc ccacactccc ctttccaatc
     6841 tagtgccttc cttgaacttt ttcctgagct gctacgtccc taatccccct tgttgggagg
     6901 attttcgtat cacccttatg ggacctgtca ccatgtcctg tactatttgg aattggtttt
     6961 ccagtctttc aacaaccgtt gtggctaact atgttttaga agggctggag gtgtgggccc
     7021 tgtcttcggg tctcaggacc caaagatcct ttagtcagtt gttgggtctt ccaagagcca
     7081 gacattaata cagattgaac tccatcagtc ccctaattgt cagcctttac ctccctccca
     7141 gagcaaggag tttagggatt ctaaagctta gtgtccacac atcattctac cagaccttag
     7201 agctttagaa gctcaatcta aaatactgta actcagcata aactattact atcactcctt
     7261 tgaactcagt ctccatgagc agtgttttgt tggaaataca tagaacggct taatgcctag
     7321 agggtggtgg atagtgaagg acggtcaagg ttatattttt gactgcttag ggattctttg
     7381 gatccaagaa acagaaatgt tcaagcggaa taaaggaggg agtggagttg tggtaaggat
     7441 gcagggtatt tcgcagaacc caggacggga agtgcctttg gttcttgggt ggagctggaa
     7501 ctgcagagct ttgcacctag tcctttctcc cgcttcacag tctgcttatg gtatatgtgg
     7561 cccccaaata ggcactctag tcctcaagtc tacaccacct tccaactctg gggatcacca
     7621 tgaacaaatt ctcaatttcc catacttaat tttttttttt tttgagatgg agtctcgctg
     7681 tgtcgcccag gctggagtgc agtggtgcag tctcaactca ccacaacctc tgcctcccag
     7741 gttcaagcag ttctctgcct caacctcccg agtagctggg attacaggcg cctgccacca
     7801 tgcccagcta atgttcatat ttttagtaga gacagggttt caccgtcttg gctaggctgg
     7861 tcttgaactc ctgaccctca tgatccaccc acctcggcct cccaaagtgc taagattaca
     7921 ggcgtgagcc accgcgcccg gcccatactt cgtattctta aaaaaaacta cactcagccc
     7981 agcacattga tcaagtatct atctctgagc agttggcctt gccagggaga gcagagatgt
     8041 ggcaggctcc ttcagctgga gacagggagc ttctcagaga agtgagcaga gactccacag
     8101 acaccctaaa aaggcttcta ctcaagaagt aaagccacta ctcctgcctt tttgcttagt
     8161 ggacaggaag gcacaggagt ttgtctggga catcatagaa attcttaggt ttaacttaat
     8221 tctggtcatt gtcttcttta tttcctgttt ttcttccctt tgtcagtctt cgcatccaag
     8281 atttcttccc tccctcttgt gggccagcct gtcctgttcc agagctagcc tgttcctggg
     8341 tagccttcct tagcctccat tcagcctcag gtcttttgcc ttcttccgtg tttatttaga
     8401 gagcagaatc taataacggg ttccactgta gccactatcc atggacttct gggtcctctt
     8461 caggtttgag tgcttgaaaa tgttcattct ctgggcttgt ggcctgtctc ctccactctc
     8521 ctcctcaccc tctcgctcct tcctgtgtga gggccgctct gcagtaatgt tctcaggcaa
     8581 gccttcctag gcacctcaga aactactttg ccagagccag taagaatata taatattgga
     8641 gcagttgcca ggatagaaat taaatataga ttccagttta ggatagagtt tttaccgaga
     8701 gctctttaga cagtatacct gtgtcttctc tggcaattgc tttcatttta gtcctatata
     8761 aaagctttcc ttttctgttt ttttttaaaa ctatgctttt gcttgcctaa atcttttgat
     8821 cttatatttc tctcatctca gagcctgtcc tgagttgtaa ggtatttcat actgccttac
     8881 ttaaaagttt tttaaactac tagagtcatt tgatacacac agaagttacc taataatcca
     8941 aagatgtcca tcaagggagg aagggtgggt catcagactt tgcctttgat gttgtagact
     9001 aggctcctga gttaagcagc agagggacag cagtgccatg tgccttcact gtgtcccagg
     9061 aaatctgggt tggttccagt gggaaatacc agtatttctt ggttctggaa agtagcaaaa
     9121 gagtaggaga tggggaaata gggatgggga gagcaagccc cgcatgtcca tggcgagtca
     9181 ggtggggagc acgggtggaa gggccggctg ttgacagaca gactaagctg tgtggtgctc
     9241 ttgccgcccc ttcctgggta cagagcttga gaaaaatgca gccgaccact ccctgtgttt
     9301 gtacagagca aagcccaaaa gccaacctca gatctcctga tttggcagct gaagaaatca
     9361 gcagagtcct gattgcctga ttcagtccca aaaatgaatg tcaggccccg ccccctcccc
     9421 accaacattg cctctcctac attctccttc tgcccctaaa tcagacagga ggccagagag
     9481 gagtattgct caatgcgtgc tatgtgcaac tcctcaggcc ttgtgccacc tccatgctga
     9541 gccctgaagc agggtgtcct gggtgcctgt gtgtcagctc cctcctctct acctacctct
     9601 gaccttcttg tgggtgaggg tggccatgct tatggccatc ttaaaactgg agaggcagag
     9661 aactacttat gagtctgtag accacgtgtt gtcttccatg gcctgtttct cctgctgtct
     9721 gggtgagtga gcctgcaacg caatgcccat gagagtaaat gcctcctgac ctaccctgct
     9781 cagcactgtt ctagtgtctt ggccttgaaa gaaaagcctg acttcctgct gacacatgtg
     9841 gtaggggcat ggcagctatg aggcacctcc tacgtctgtt ttctggctgt ggtgacttgg
     9901 gatttttaac cttatatatc tttttccttt actcaaaaca aaacaatttt tagcacactg
     9961 aaaaaaaaaa aaagccaaat gttttgtgcc tttctaaggc agcactgtat cccaggctgc
    10021 attttaggac ttaatatgga aataccagag tctgagctcc tctaccttga gtttcattag
    10081 tccttagtgt ctaggagaca ggaaagaatg ctctctgtga ctggagaggt gacatgcagg
    10141 tgcagtgtgt ctggagtccc tttcccctgc tgtgagactt cagtggagga gagaagcatt
    10201 gtaccctggg atcatttggt tggttccaat cacaagctta gttatcaggt tgcatgcctt
    10261 gtctcctgca aaagacagaa tgtttcacaa ttcccaggta aactctggac cattccaagt
    10321 gtcctagcct tctgatgaca ttaattacct agttgtgtcg aggagtatag gatggactct
    10381 cctgagaagg ggaggttggt ggctttgtct tttctttttg ctggatcctg aactggtcta
    10441 gacctcctgc ccccaccccc cagcccccat cagatgtggc tggcctttca tttgaaggct
    10501 tcagacttaa agcattaagc agctagtgcc ctctgcaggg cctggtttcc ccagggaagg
    10561 gcagcaagga acatgggacc agaagcctgt cctcagtaat gtgactatag tgagctttag
    10621 caaaagtttt tctatataat gacatcttac ttatctttta ccctttcctc agttttcccc
    10681 tgcctttaac taataaagaa ttgggagaca gaaattttaa agtcctcctt attcaagatt
    10741 ttgaaattct tagcctggga gtgctggaga gaacctgatg ctttctccag aatgaagagt
    10801 cccaatttgt atatcagtgt taagaagaaa acaaaacaaa cacataggtg agattttcgt
    10861 ggactatttt aaaaatgtgt cattaatata aaaaatttat attagcagta tttaatcatt
    10921 ctcacctgta aagaataaga aaaacagaag gtaaatattc ttacagagaa tagcagagct
    10981 ttaagattca ttttcatttt aagtccattt tattttgcca gtgtattaat gtttagaagt
    11041 ctgttttact aatgttattt attaattttt tttcatttcc atacacagtt agttaactaa
    11101 agagcttttt caagcaccca tgtctgtaaa aaaatatttt taaataaagt ttcttttgtt
    11161 gtagcaga
//
