LOCUS       NM_002392               7490 bp    mRNA    linear   PRI 21-MAR-2025
DEFINITION  Homo sapiens MDM2 proto-oncogene (MDM2), transcript variant 1,
            mRNA.
ACCESSION   NM_002392
VERSION     NM_002392.6
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 7490)
  AUTHORS   Sam,K.K., Gan,C.P., Yee,P.S., Chong,C.E., Lim,K.P., Karen-Ng,L.P.,
            Chang,W.S., Nathan,S., Rahman,Z.A., Ismail,S.M. and Cheong,S.C.
  TITLE     Novel MDM2 splice variants identified from oral squamous cell
            carcinoma
  JOURNAL   Oral Oncol 48 (11), 1128-1135 (2012)
   PUBMED   22705356
  REMARK    GeneRIF: MDM2 splice variants is significantly assiciated with oral
            squamous cell carcinoma and increased the risk of oral squamous
            cell carcinoma development
REFERENCE   2  (bases 1 to 7490)
  AUTHORS   Dutertre,M., Sanchez,G., De Cian,M.C., Barbier,J., Dardenne,E.,
            Gratadou,L., Dujardin,G., Le Jossic-Corcos,C., Corcos,L. and
            Auboeuf,D.
  TITLE     Cotranscriptional exon skipping in the genotoxic stress response
  JOURNAL   Nat Struct Mol Biol 17 (11), 1358-1366 (2010)
   PUBMED   20972445
REFERENCE   3  (bases 1 to 7490)
  AUTHORS   Jeyaraj,S., O'Brien,D.M. and Chandler,D.S.
  TITLE     MDM2 and MDM4 splicing: an integral part of the cancer spliceome
  JOURNAL   Front Biosci (Landmark Ed) 14 (7), 2647-2656 (2009)
   PUBMED   19273224
  REMARK    Review article
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 7490)
  AUTHORS   Cheng,T.H. and Cohen,S.N.
  TITLE     Human MDM2 isoforms translated differentially on constitutive
            versus p53-regulated transcripts have distinct functions in the
            p53/MDM2 and TSG101/MDM2 feedback control loops
  JOURNAL   Mol Cell Biol 27 (1), 111-119 (2007)
   PUBMED   17060450
  REMARK    GeneRIF: analysis of mechanism of formation of the principal MDM2
            isoforms, differential effects of p53 on the production of these
            isoforms, and differential abilities of human MDM2 isoforms as
            regulators of the MDM2/TSG101 and p53/MDM2 feedback control loops
REFERENCE   5  (bases 1 to 7490)
  AUTHORS   Liang,H., Atkins,H., Abdel-Fattah,R., Jones,S.N. and Lunec,J.
  TITLE     Genomic organisation of the human MDM2 oncogene and relationship to
            its alternatively spliced mRNAs
  JOURNAL   Gene 338 (2), 217-223 (2004)
   PUBMED   15315825
  REMARK    GeneRIF: MDM2 gene spans approximately 33 kb and is divided into 12
            exons.
REFERENCE   6  (bases 1 to 7490)
  AUTHORS   Bartel,F., Pinkert,D., Fiedler,W., Kappler,M., Wurl,P., Schmidt,H.
            and Taubert,H.
  TITLE     Expression of alternatively and aberrantly spliced transcripts of
            the MDM2 mRNA is not tumor-specific
  JOURNAL   Int J Oncol 24 (1), 143-151 (2004)
   PUBMED   14654951
REFERENCE   7  (bases 1 to 7490)
  AUTHORS   Jin,X., Turcott,E., Englehardt,S., Mize,G.J. and Morris,D.R.
  TITLE     The two upstream open reading frames of oncogene mdm2 have
            different translational regulatory properties
  JOURNAL   J Biol Chem 278 (28), 25716-25721 (2003)
   PUBMED   12730202
  REMARK    GeneRIF: two upstream open reading frames of oncogene mdm2 may play
            a fundamental role in regulating expression of the mdm2 gene
REFERENCE   8  (bases 1 to 7490)
  AUTHORS   Bartel,F., Taubert,H. and Harris,L.C.
  TITLE     Alternative and aberrant splicing of MDM2 mRNA in human cancer
  JOURNAL   Cancer Cell 2 (1), 9-15 (2002)
   PUBMED   12150820
  REMARK    GeneRIF: MDM2 has been characterized as a protein that binds to and
            facilitates degradation of the tumor suppressor p53.  Splice
            variants of MDM2 transcripts have been identified in both tumors
            and normal tissues.
            Review article
REFERENCE   9  (bases 1 to 7490)
  AUTHORS   Brown,C.Y., Mize,G.J., Pineda,M., George,D.L. and Morris,D.R.
  TITLE     Role of two upstream open reading frames in the translational
            control of oncogene mdm2
  JOURNAL   Oncogene 18 (41), 5631-5637 (1999)
   PUBMED   10523842
REFERENCE   10 (bases 1 to 7490)
  AUTHORS   Landers,J.E., Cassel,S.L. and George,D.L.
  TITLE     Translational enhancement of mdm2 oncogene expression in human
            tumor cells containing a stabilized wild-type p53 protein
  JOURNAL   Cancer Res 57 (16), 3562-3568 (1997)
   PUBMED   9270029
REFERENCE   11 (bases 1 to 7490)
  AUTHORS   Sigalas,I., Calvert,A.H., Anderson,J.J., Neal,D.E. and Lunec,J.
  TITLE     Alternatively spliced mdm2 transcripts with loss of p53 binding
            domain sequences: transforming ability and frequent detection in
            human cancer
  JOURNAL   Nat Med 2 (8), 912-917 (1996)
   PUBMED   8705862
REFERENCE   12 (bases 1 to 7490)
  AUTHORS   Zauberman,A., Flusberg,D., Haupt,Y., Barak,Y. and Oren,M.
  TITLE     A functional p53-responsive intronic promoter is contained within
            the human mdm2 gene
  JOURNAL   Nucleic Acids Res 23 (14), 2584-2592 (1995)
   PUBMED   7651818
REFERENCE   13 (bases 1 to 7490)
  AUTHORS   Olson,D.C., Marechal,V., Momand,J., Chen,J., Romocki,C. and
            Levine,A.J.
  TITLE     Identification and characterization of multiple mdm-2 proteins and
            mdm-2-p53 protein complexes
  JOURNAL   Oncogene 8 (9), 2353-2360 (1993)
   PUBMED   7689721
REFERENCE   14 (bases 1 to 7490)
  AUTHORS   Oliner,J.D., Kinzler,K.W., Meltzer,P.S., George,D.L. and
            Vogelstein,B.
  TITLE     Amplification of a gene encoding a p53-associated protein in human
            sarcomas
  JOURNAL   Nature 358 (6381), 80-83 (1992)
   PUBMED   1614537
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC025423.32.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Oct 27, 2020 this sequence version replaced NM_002392.5.
            
            Summary: This gene encodes a nuclear-localized E3 ubiquitin ligase.
            The encoded protein can promote tumor formation by targeting tumor
            suppressor proteins, such as p53, for proteasomal degradation. This
            gene is itself transcriptionally-regulated by p53. Overexpression
            or amplification of this locus is detected in a variety of
            different cancers. There is a pseudogene for this gene on
            chromosome 2. Alternative splicing results in a multitude of
            transcript variants, many of which may be expressed only in tumor
            cells. [provided by RefSeq, Jun 2013].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (a).
            
            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 :: SRR14038191.1492213.1,
                                           SRR11853567.7449.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000258149.11/ ENSP00000258149.6
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            regulatory uORF        :: PMID: 10523842
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-315               AC025423.32        140987-141301       c
            316-400             AC025423.32        140186-140270       c
            401-475             AC025423.32        135850-135924       c
            476-609             AC025423.32        132533-132666       c
            610-659             AC025423.32        129104-129153       c
            660-727             AC025423.32        125048-125115       c
            728-824             AC025423.32        124827-124923       c
            825-985             AC025423.32        120547-120707       c
            986-1141            AC025423.32        113494-113649       c
            1142-1219           AC025423.32        112729-112806       c
            1220-7490           AC025423.32        103934-110204       c
FEATURES             Location/Qualifiers
     source          1..7490
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q15"
     gene            1..7490
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /note="MDM2 proto-oncogene"
                     /db_xref="GeneID:4193"
                     /db_xref="HGNC:HGNC:6973"
                     /db_xref="MIM:164785"
     exon            1..315
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     regulatory      71..116
                     /regulatory_class="uORF"
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:10523842]"
                     /note="this uORF is predicted to encode a 14 aa peptide
                     (PMID:10523842, 12730202)"
     regulatory      205..249
                     /regulatory_class="uORF"
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:10523842]"
                     /note="this uORF is predicted to encode a 14 aa peptide
                     (PMID:10523842, 12730202)"
     CDS             302..1795
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /EC_number="2.3.2.27"
                     /note="isoform a is encoded by transcript variant 1;
                     double minute 2, human homolog of; p53-binding protein;
                     oncoprotein Mdm2; Mdm2, transformed 3T3 cell double minute
                     2, p53 binding protein; Mdm2, p53 E3 ubiquitin protein
                     ligase homolog; MDM2 oncogene, E3 ubiquitin protein
                     ligase; MDM2 proto-oncogene, E3 ubiquitin protein ligase"
                     /codon_start=1
                     /product="E3 ubiquitin-protein ligase Mdm2 isoform a"
                     /protein_id="NP_002383.2"
                     /db_xref="CCDS:CCDS8986.2"
                     /db_xref="GeneID:4193"
                     /db_xref="HGNC:HGNC:6973"
                     /db_xref="MIM:164785"
                     /translation="MVRSRQMCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLL
                     KSVGAQKDTYTMKEVLFYLGQYIMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEH
                     RKIYTMIYRNLVVVNQQESSDSGTSVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVS
                     RPSTSSRRRAISETEENSDELSGERQRKRHKSDSISLSFDESLALCVIREICCERSSS
                     SESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSEDYSLSEEGQELSD
                     EDDEVYQVTVYQAGESDTDSFEEDPEISLADYWKCTSCNEMNPPLPSHCNRCWALREN
                     WLPEDKGKDKGEISEKAKLENSTQAEEGFDVPDCKKTIVNDSRESCVEENDDKITQAS
                     QSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQDKEESVESSLPLNAIEPCVICQGR
                     PKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQPIQMIVLTYFP"
     exon            316..400
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     exon            401..475
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     exon            476..609
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     exon            610..659
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     exon            660..727
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     exon            728..824
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     exon            825..985
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     exon            986..1141
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1142..1219
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1220..7490
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /inference="alignment:Splign:2.1.0"
     regulatory      6109..6114
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /note="hexamer: AATAAA"
     polyA_site      6141
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /note="major polyA site"
     regulatory      6174..6179
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /note="hexamer: AATAGA"
     polyA_site      6213
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
     regulatory      7358..7363
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
                     /note="hexamer: AATAAA"
     polyA_site      7380
                     /gene="MDM2"
                     /gene_synonym="ACTFS; hdm2; HDMX; LSKB"
ORIGIN      
        1 gggcgcgcac cgaggcaccg cggcgagctt ggctgcttct ggggcctgtg tggccctgtg
       61 tgtcggaaag atggagcaag aagccgagcc cgaggggcgg ccgcgacccc tctgaccgag
      121 atcctgctgc tttcgcagcc aggagcaccg tccctccccg gattagtgcg tacgagcgcc
      181 cagtgccctg gcccggagag tggaatgatc cccgaggccc agggcgtcgt gcttccgcgc
      241 gccccgtgaa ggaaactggg gagtcttgag ggacccccga ctccaagcgc gaaaaccccg
      301 gatggtgagg agcaggcaaa tgtgcaatac caacatgtct gtacctactg atggtgctgt
      361 aaccacctca cagattccag cttcggaaca agagaccctg gttagaccaa agccattgct
      421 tttgaagtta ttaaagtctg ttggtgcaca aaaagacact tatactatga aagaggttct
      481 tttttatctt ggccagtata ttatgactaa acgattatat gatgagaagc aacaacatat
      541 tgtatattgt tcaaatgatc ttctaggaga tttgtttggc gtgccaagct tctctgtgaa
      601 agagcacagg aaaatatata ccatgatcta caggaacttg gtagtagtca atcagcagga
      661 atcatcggac tcaggtacat ctgtgagtga gaacaggtgt caccttgaag gtgggagtga
      721 tcaaaaggac cttgtacaag agcttcagga agagaaacct tcatcttcac atttggtttc
      781 tagaccatct acctcatcta gaaggagagc aattagtgag acagaagaaa attcagatga
      841 attatctggt gaacgacaaa gaaaacgcca caaatctgat agtatttccc tttcctttga
      901 tgaaagcctg gctctgtgtg taataaggga gatatgttgt gaaagaagca gtagcagtga
      961 atctacaggg acgccatcga atccggatct tgatgctggt gtaagtgaac attcaggtga
     1021 ttggttggat caggattcag tttcagatca gtttagtgta gaatttgaag ttgaatctct
     1081 cgactcagaa gattatagcc ttagtgaaga aggacaagaa ctctcagatg aagatgatga
     1141 ggtatatcaa gttactgtgt atcaggcagg ggagagtgat acagattcat ttgaagaaga
     1201 tcctgaaatt tccttagctg actattggaa atgcacttca tgcaatgaaa tgaatccccc
     1261 ccttccatca cattgcaaca gatgttgggc ccttcgtgag aattggcttc ctgaagataa
     1321 agggaaagat aaaggggaaa tctctgagaa agccaaactg gaaaactcaa cacaagctga
     1381 agagggcttt gatgttcctg attgtaaaaa aactatagtg aatgattcca gagagtcatg
     1441 tgttgaggaa aatgatgata aaattacaca agcttcacaa tcacaagaaa gtgaagacta
     1501 ttctcagcca tcaacttcta gtagcattat ttatagcagc caagaagatg tgaaagagtt
     1561 tgaaagggaa gaaacccaag acaaagaaga gagtgtggaa tctagtttgc cccttaatgc
     1621 cattgaacct tgtgtgattt gtcaaggtcg acctaaaaat ggttgcattg tccatggcaa
     1681 aacaggacat cttatggcct gctttacatg tgcaaagaag ctaaagaaaa ggaataagcc
     1741 ctgcccagta tgtagacaac caattcaaat gattgtgcta acttatttcc cctagttgac
     1801 ctgtctataa gagaattata tatttctaac tatataaccc taggaattta gacaacctga
     1861 aatttattca catatatcaa agtgagaaaa tgcctcaatt cacatagatt tcttctcttt
     1921 agtataattg acctactttg gtagtggaat agtgaatact tactataatt tgacttgaat
     1981 atgtagctca tcctttacac caactcctaa ttttaaataa tttctactct gtcttaaatg
     2041 agaagtactt ggtttttttt tttcttaaat atgtatatga catttaaatg taacttatta
     2101 ttttttttga gaccgagtct tgctctgtta cccaggctgg agtgcagtgg cgtgatcttg
     2161 gctcactgca agctctgcct cccgggttcg caccattctc ctgcctcagc ctcccaatta
     2221 gcttggccta cagtcatctg ccaccacacc tggctaattt tttgtacttt tagtagagac
     2281 agggtttcac cgtgttagcc aggatggtct cgatctcctg acctcgtgat ccgcccacct
     2341 cggcctccca aagtgctggg attacaggca tgagccaccg cgtccggcct aaatgtcact
     2401 tagtaccttt gatataaaga gaaaatgtgt gaaagattta gttttttgtt tttttgtttg
     2461 tttgtttgtt tgtttgtttt gagatgagtc tctctgtcgc ccaggctgga gtgcagtgtc
     2521 atgatctagc agtctccgct tcccgggttc aagccattct cctggctcag cctctggagc
     2581 agctgggatt acaggcatgc accaccatgc ccagctaatt tttgtatttt tagtagagat
     2641 agggtttcac catgttggcc aggctggtca cgaactcctg acctcaagtg aggtcacccg
     2701 cctcggcctc ccgaagtgct gggattgcag atgtgagcca ccatgtccag ccaagaatta
     2761 gtatttaaat tttagatact cttttttttt tttttttttt ttttttttga gacagagtct
     2821 tgctccatca cccatgctag agtgcagtgg agtgatctcg gctcactgca acttccgcct
     2881 tctgggttca agctattctc ctgcctcagc cttccaagta actgggatta caggcatgta
     2941 ccaccatacc agctgatttt tttgtatttt tagtaaagac agggtttcac catgttagcc
     3001 aggctgatct tgaactccta aactcaagtg atctactcac ctcagcctcc caaaatgctg
     3061 ggattacaga tgtgaggcac ctggcctcag atttttgata ctcttaaacc ttctgatcct
     3121 tagtttctct ctccaaaata ctctttctag gttaaaaaaa aaaaggctct tatatttggt
     3181 gctatgtaaa tgaaaatgtt ttttaggttt tcttgattta acaatagaga cagggtctcc
     3241 ctgtgttgcc caggctggtc tcgaactcct gggctcaaga gatcctcctg tcttggcctc
     3301 gcaaagtgct aagtaggatt acaggcgtta gccaccacac ccggctgtaa aaatgtactt
     3361 attctccagc ctcttttgta taaaccatag taagggatgg gagtaatgat gttatctgtg
     3421 aaaatagcca ccatttaccc gtaagacaaa acttgttaaa gcctcctgag tctaacctag
     3481 attacatcag gccctttttc acacacaaaa aaatccttta tgggatttaa tggaatctgt
     3541 tgtttccccc taagttgaaa aacaactcta agacacttta aagtaccttc ttggcctggg
     3601 ttacatggtt cccagcctag gtttcagact tttgcttaag gccagtttta gaaacccgtg
     3661 aattcagaaa agttaattca gaaatttgat aaacagaatt gttatttaaa aactaactgg
     3721 aaagattgtt aagttctttc tgaattattc agaaattatg catcattttc cttcaagaat
     3781 gacagggtca gcatgtggaa ttccaagata cctcttgact tcctctcaag ctccgtgttt
     3841 ggtcagtgga ggcccatccg agctcagcac tgagaagtgt tagtttcttt gggacccatc
     3901 taccctgacc acatcatgat gttcatctgc agctgttgca aggtgttcag attgtataaa
     3961 cataaatgtc acaaaaactt taaaagaagt gcaattctca aaaggttagg tggactaaag
     4021 cattctgtaa agcaactgct aataatgagc ttacagtgga tttgaatttg aaaaatatag
     4081 taacaagcct gtcaaatatc tgcaagaact atggaataaa actactgatg cagtgaagac
     4141 agttgaaaag atcaaacaaa tgccaagcta tatttataat gaacaaattc aagaaaaagg
     4201 actacggaaa gttcaggaca tcaaagaagt caggcaaaac tcatcttgac ccctgttgca
     4261 ggcaaaggaa cgcagctgga agaaaagatg atataacagt taacaggatg cagacatggc
     4321 agaggtttcc taaaaatctc attatctata accatttcta tatttacatt tgaaaatctc
     4381 ctttggagac ttagaacctc taaattattg acttattttt tatataaggt cactccgatg
     4441 aaaggtgatt acaaaatcat ctacattgct gtctacaaaa cagataatat ggatgtttga
     4501 tcgcatctca ttgttaactc tttactgata tgtttgtaaa tacagaagtg aaatgtggac
     4561 ataaaatagt tacgctattt ggttaatggt actagacaac atgtaattaa tgacattcaa
     4621 aaatttatgg ctagtgatat atataaagta aaattttctt tgcagtaaaa tatgcccttt
     4681 attatagaag ggaggatata aggaaccaac agtttgtatg aaaatagctc aaataatatc
     4741 ttttattttg attttaatat ttcttatttt ggtttattag tgtcttagaa caaaatggcc
     4801 ttatataatg aagcctagtt atgctggact gttttgatct cttttaattg ttctgacaga
     4861 tagttgggga tgagagccga ataaggtttg cctgaaataa ctgacactat ataatttctg
     4921 ctttggcaaa tactaagttc taacttgtca ttcctggtag aacaagcttt atttttcgag
     4981 cctagcaatg atctagaagc agatgttatc tcagtgcctt ttgcaatttg ttgtgtgggt
     5041 tttttttttt ttaaagccac acaataattt tggaaaacaa tgtatgggta gaacatgtgt
     5101 ctgttaattg cacacaaaac cacttttaat gggtacagag ttaaatttga aggaataagt
     5161 tctagctgaa gtattatgaa ctccaaataa tgctttgagg acctccaaag gtaaaagtac
     5221 taatcccttt ggccatttat tgagagagag agagagagag agtagggtga ctatagttaa
     5281 tgtattgaat gttcttgcta caaataaatg atatttgagc tgatgggtgt gctaattaca
     5341 ctgatttgat caatacccat tgtatgtgaa acagtacata caccatattt acaattatgt
     5401 atttaacatt taaaatttct aatataagta tctctcaaac tgtggattaa cttcttgatt
     5461 tatatttaaa tatgaatctt aagcaaaaca gtgaaaataa ccatcttgat ttagtgtttt
     5521 tctcccatat gtgaattgta tatacttagg tgaagacaat aaaatcaact gaactgtaag
     5581 cttagaatag gactgaggta attctgcaca gcaactttac taatggtaca ttgttgcttc
     5641 aaaactctct ctctctctct ctgtctgtct caataaatgg ccaaagggat tagtagttta
     5701 cctgtggagg tcctccaagc attatttgga gttgataata cttcagctac aaccaagcag
     5761 aatctctttt ttttggaggt cctcgaagca ttatttggag ttgataatac ttcagcttca
     5821 atttggagtt gataatattt cagctagaac ctagtagaat ctgttttttt cctttggagg
     5881 tcctcaaagc attattggag ttcataatac tgaagctaga accaagcaga atctgttttt
     5941 ttctgaggag tatcggtagc ataaatgtga ttataaacat agtacacttg atatatggag
     6001 gcagtgacag ctatttttac aaaatttaaa tctgcaaatg gattcaacat gtttatgggt
     6061 tattaaaatt gtctgatttc ttaggttctt tatagtacac gtgttgaaaa taaatgatta
     6121 agaattgttt caagaatgca attatttgat cttaaatttt tatgagttgt taaaatagaa
     6181 attatttgaa tatcatatat ttgggtaaca aaaggcacaa gtctgaatgt gtttcttttt
     6241 ctggaatggc catgcctgcc cactttagaa atacaaatat cactgggcag cttgaagcag
     6301 ttgggagcct ccaatgagag caacttgaga gaatgatgtt gcaagttagt aggagtaaga
     6361 aatgctgtgt tctccctgtc ttctcttagg tcacatggca gcctggccta agtgatcgtg
     6421 aatggtctat aagggaggta gctgggacag ggaggggagt ttgggctagc caccgtacca
     6481 cttgtcagcg tgaaaagtaa gattgtaatt gcctgtttag ttttctgcct catctttgaa
     6541 agttccacca agctgggaac ctcttgattg tgaggcacaa atgtaagtac atcagaaaaa
     6601 aacaaaaaaa ctggctttaa agcaggagct tgtgggcccc taagccagac ggggactagc
     6661 ttttggcatt atataattaa gattttttaa atccttaata agggttttat tttattttta
     6721 tttatttttt gagacggagt cttgctctgt ggctcaggct ggagtacagt ggtgcaatct
     6781 tggctcactg caacctctgc ctcctggctg tgttcaagtg gttctgcttc agcctcccaa
     6841 gtagctgggg ttagagcacc ctgtcaccac gccccgctaa tttttgtatt tctagcagag
     6901 atgaagtttc actatgttgg ccaggctggg ctcaaactcc tgacctcaag tgatctgccc
     6961 gccttggccc cccaaagtgc tgtgattaca ggcgtgagcc gccacgccca gcctaataag
     7021 ggttttaaag ataattagtg tgtaggtctg taggcttatg atggtaacca caagttgtta
     7081 atggcattgt gaaaagtttt tagttgcgct ttatgggtgg atgctgaatt acattttgat
     7141 ttgatactta taaaaagaaa aagtatttct tcagcttaaa aaattgttta aaagtttgtg
     7201 atcatattgt ctaccatgta gccagctttc aattatatgt aagagggact ttttgacatt
     7261 tacaaataat actttgaggt agatatctga aagcaccagc acttggaagg tgttcagaag
     7321 taacaaatta taaaatgagc taacaaacga aaggcaaaat aaaaccgtaa agcaagcaga
     7381 tgggaggcgt gttcagtaac ttattcataa tgcatctgaa atgattgctg tactcaaata
     7441 tttaacgtta gagtaatagt attttgaatg aaaaccatag ttgattgtct
//
