LOCUS       NM_018077              15507 bp    mRNA    linear   PRI 20-SEP-2024
DEFINITION  Homo sapiens RNA binding motif protein 28 (RBM28), transcript
            variant 1, mRNA.
ACCESSION   NM_018077
VERSION     NM_018077.3
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 15507)
  AUTHORS   Lin,X., Zhou,L., Zhong,J., Zhong,L., Zhang,R., Kang,T. and Wu,Y.
  TITLE     RNA-binding protein RBM28 can translocate from the nucleolus to the
            nucleoplasm to inhibit the transcriptional activity of p53
  JOURNAL   J Biol Chem 298 (2), 101524 (2022)
   PUBMED   34953860
  REMARK    GeneRIF: RNA-binding protein RBM28 can translocate from the
            nucleolus to the nucleoplasm to inhibit the transcriptional
            activity of p53.
REFERENCE   2  (bases 1 to 15507)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   3  (bases 1 to 15507)
  AUTHORS   Bryant,C.J., Lorea,C.F., de Almeida,H.L. Jr., Weinert,L.,
            Vedolin,L., Pinto E Vairo,F. and Baserga,S.J.
  TITLE     Biallelic splicing variants in the nucleolar 60S assembly factor
            RBM28 cause the ribosomopathy ANE syndrome
  JOURNAL   Proc Natl Acad Sci U S A 118 (19) (2021)
   PUBMED   33941690
  REMARK    GeneRIF: Biallelic splicing variants in the nucleolar 60S assembly
            factor RBM28 cause the ribosomopathy ANE syndrome.
REFERENCE   4  (bases 1 to 15507)
  AUTHORS   Fasci,D., van Ingen,H., Scheltema,R.A. and Heck,A.J.R.
  TITLE     Histone Interaction Landscapes Visualized by Crosslinking Mass
            Spectrometry in Intact Cell Nuclei
  JOURNAL   Mol Cell Proteomics 17 (10), 2018-2033 (2018)
   PUBMED   30021884
REFERENCE   5  (bases 1 to 15507)
  AUTHORS   McCann,K.L., Teramoto,T., Zhang,J., Tanaka Hall,T.M. and
            Baserga,S.J.
  TITLE     The molecular basis for ANE syndrome revealed by the large
            ribosomal subunit processome interactome
  JOURNAL   Elife 5, e16381 (2016)
   PUBMED   27077951
  REMARK    GeneRIF: The authors conclude that the ANE syndrome mutation
            generates defective RBM28 protein folding which abrogates
            protein-protein interactions and causes faulty pre-large subunit
            rRNA processing, thus revealing one aspect of the molecular basis
            of this human disease.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 15507)
  AUTHORS   Nousbeck,J., Spiegel,R., Ishida-Yamamoto,A., Indelman,M.,
            Shani-Adir,A., Adir,N., Lipkin,E., Bercovici,S., Geiger,D., van
            Steensel,M.A., Steijlen,P.M., Bergman,R., Bindereif,A., Choder,M.,
            Shalev,S. and Sprecher,E.
  TITLE     Alopecia, neurological defects, and endocrinopathy syndrome caused
            by decreased expression of RBM28, a nucleolar protein associated
            with ribosome biogenesis
  JOURNAL   Am J Hum Genet 82 (5), 1114-1121 (2008)
   PUBMED   18439547
  REMARK    GeneRIF: A loss-of-function mutation is found in RBM28, encoding a
            nucleolar protein in patients with alopecia, progressive
            neurological defects, and endocrinopathy (ANE syndrome).
REFERENCE   7  (bases 1 to 15507)
  AUTHORS   Damianov,A., Kann,M., Lane,W.S. and Bindereif,A.
  TITLE     Human RBM28 protein is a specific nucleolar component of the
            spliceosomal snRNPs
  JOURNAL   Biol Chem 387 (10-11), 1455-1460 (2006)
   PUBMED   17081119
  REMARK    GeneRIF: RBM28 is a common nucleolar component of the spliceosomal
            ribonucleoprotein complexes, possibly coordinating their transition
            through the nucleolus
REFERENCE   8  (bases 1 to 15507)
  AUTHORS   Andersen,J.S., Lam,Y.W., Leung,A.K., Ong,S.E., Lyon,C.E.,
            Lamond,A.I. and Mann,M.
  TITLE     Nucleolar proteome dynamics
  JOURNAL   Nature 433 (7021), 77-83 (2005)
   PUBMED   15635413
REFERENCE   9  (bases 1 to 15507)
  AUTHORS   Scherl,A., Coute,Y., Deon,C., Calle,A., Kindbeiter,K.,
            Sanchez,J.C., Greco,A., Hochstrasser,D. and Diaz,J.J.
  TITLE     Functional proteomic analysis of human nucleolus
  JOURNAL   Mol Biol Cell 13 (11), 4100-4109 (2002)
   PUBMED   12429849
REFERENCE   10 (bases 1 to 15507)
  AUTHORS   Andersen,J.S., Lyon,C.E., Fox,A.H., Leung,A.K., Lam,Y.W., Steen,H.,
            Mann,M. and Lamond,A.I.
  TITLE     Directed proteomic analysis of the human nucleolus
  JOURNAL   Curr Biol 12 (1), 1-11 (2002)
   PUBMED   11790298
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC010655.7 and AC018635.10.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 20, 2019 this sequence version replaced NM_018077.2.
            
            Summary: The protein encoded by this gene is a specific nucleolar
            component of the spliceosomal small nuclear ribonucleoprotein
            (snRNP)complexes . It specifically associates with U1, U2, U4, U5,
            and U6 small nuclear RNAs (snRNAs), possibly coordinating their
            transition through the nucleolus. Mutation in this gene causes
            alopecia, progressive neurological defects, and endocrinopathy (ANE
            syndrome), a pleiotropic and clinically heterogeneous disorder.
            Alternatively spliced transcript variants encoding different
            isoforms have been found for this gene. [provided by RefSeq, Oct
            2009].
            
            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 :: AK001239.1, SRR3476690.231180.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000223073.6/ ENSP00000223073.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-233               AC010655.7         13425-13657         c
            234-392             AC010655.7         9382-9540           c
            393-487             AC010655.7         8976-9070           c
            488-563             AC010655.7         8475-8550           c
            564-656             AC010655.7         7999-8091           c
            657-728             AC010655.7         6880-6951           c
            729-924             AC010655.7         5596-5791           c
            925-1061            AC010655.7         5292-5428           c
            1062-1134           AC010655.7         3039-3111           c
            1135-1244           AC010655.7         567-676             c
            1245-1318           AC018635.10        104206-104279       c
            1319-1454           AC018635.10        102947-103082       c
            1455-1519           AC018635.10        101915-101979       c
            1520-1678           AC018635.10        99654-99812         c
            1679-1828           AC018635.10        96345-96494         c
            1829-1903           AC018635.10        96047-96121         c
            1904-2160           AC018635.10        93152-93408         c
            2161-2260           AC018635.10        91563-91662         c
            2261-15507          AC018635.10        76073-89319         c
FEATURES             Location/Qualifiers
     source          1..15507
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q32.1"
     gene            1..15507
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /note="RNA binding motif protein 28"
                     /db_xref="GeneID:55131"
                     /db_xref="HGNC:HGNC:21863"
                     /db_xref="MIM:612074"
     exon            1..233
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     CDS             116..2395
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /note="isoform 1 is encoded by transcript variant 1;
                     2810480G15Rik"
                     /codon_start=1
                     /product="RNA-binding protein 28 isoform 1"
                     /protein_id="NP_060547.2"
                     /db_xref="CCDS:CCDS5801.1"
                     /db_xref="GeneID:55131"
                     /db_xref="HGNC:HGNC:21863"
                     /db_xref="MIM:612074"
                     /translation="MAGLTLFVGRLPPSARSEQLEELFSQVGPVKQCFVVTEKGSKAC
                     RGFGYVTFSMLEDVQRALKEITTFEGCKINVTVAKKKLRNKTKEKGKNENSECPKKEP
                     KAKKAKVADKKARLIIRNLSFKCSEDDLKTVFAQFGAVLEVNIPRKPDGKMRGFGFVQ
                     FKNLLEAGKALKGMNMKEIKGRTVAVDWAVAKDKYKDTQSVSAIGEEKSHESKHQESV
                     KKKGREEEDMEEEENDDDDDDDDEEDGVFDDEDEEEENIESKVTKPVQIQKRAVKRPA
                     PAKSSDHSEEDSDLEESDSIDDGEELAQSDTSTEEQEDKAVQVSNKKKRKLPSDVNEG
                     KTVFIRNLSFDSEEEELGELLQQFGELKYVRIVLHPDTEHSKGCAFAQFMTQEAAQKC
                     LLAASPENEAGGLKLDGRQLKVDLAVTRDEAAKLQTTKVKKPTGTRNLYLAREGLIRA
                     GTKAAEGVSAADMAKRERFELLKHQKLKDQNIFVSRTRLCLHNLPKAVDDKQLRKLLL
                     SATSGEKGVRIKECRVMRDLKGVHGNMKGQSLGYAFAEFQEHEHALKALRLINNNPEI
                     FGPLKRPIVEFSLEDRRKLKMKELRIQRSLQKMRSKPATGEPQKGQPEPAKDQQQKAA
                     QHHTEEQSKVPPEQKRKAGSTSWTGFQTKAEVEQVELPDGKKRRKVLALPSHRGPKIR
                     LRDKGKVKPVHPKKPKPQINQWKQEKQQLSSEQVSRKKAKGNKTETRFNQLVEQYKQK
                     LLGPSKGAPLAKRSKWFDS"
     exon            234..392
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            393..487
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            488..563
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            564..656
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            657..728
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            729..924
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            925..1061
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1062..1134
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1135..1244
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1245..1318
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1319..1454
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1455..1519
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1520..1678
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1679..1828
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1829..1903
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1904..2160
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            2161..2260
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     exon            2261..15507
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /inference="alignment:Splign:2.1.0"
     polyA_site      2713
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /note="major polyA site"
     polyA_site      2809
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /note="major polyA site"
     regulatory      6841..6846
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /note="hexamer: AATAAA"
     polyA_site      6861
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
     regulatory      8986..8991
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /note="hexamer: AATAAA"
     polyA_site      9016
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
     regulatory      9054..9059
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /note="hexamer: AATAAA"
     polyA_site      9075
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
     regulatory      9117..9122
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /note="hexamer: AATAAA"
     polyA_site      9142
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
     regulatory      10415..10420
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /note="hexamer: AATAAA"
     polyA_site      10436
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
     regulatory      14623..14628
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
                     /note="hexamer: AATAAA"
     polyA_site      14656
                     /gene="RBM28"
                     /gene_synonym="ANES; NOP4"
ORIGIN      
        1 acttccggaa tctctcggcg tgtgagcttg gttgtcctac caaagccagc gtttcggctc
       61 gcgtgcgccg gcctagtttg ctcgcgtcct cacgcgcttt gggtttcccg gtctcatggc
      121 cggcctgacc ttatttgtgg gccgcctccc gccctcggcc cgcagtgagc agctggagga
      181 actgttcagt caggtggggc cggtgaagca gtgcttcgtg gtgactgaaa aagggagtaa
      241 ggcatgtcga ggctttggct atgtcacttt ttcaatgctg gaagatgttc agagggccct
      301 caaggagatt accacctttg aaggttgcaa gatcaacgtg actgttgcca agaaaaaact
      361 gaggaacaag acaaaggaaa aggggaaaaa tgaaaactca gagtgcccaa agaaggagcc
      421 gaaggctaaa aaagccaaag tggcagataa gaaagccaga ttaattattc ggaacctgag
      481 ctttaagtgt tcagaagatg acttgaagac agtatttgct caatttggag ctgtcctgga
      541 agtaaatatc cctaggaaac cagatgggaa gatgcgcggt tttggttttg ttcagttcaa
      601 aaacctccta gaagcaggta aagctctcaa aggcatgaac atgaaagaga taaaaggccg
      661 gacagtggct gtggattggg ccgtggcaaa ggataaatat aaagatacac agtctgtttc
      721 tgctataggt gaggaaaaga gccatgaatc taaacatcag gaatcagtta aaaagaaggg
      781 cagagaggaa gaggatatgg aagaggaaga aaacgatgat gatgacgatg atgatgatga
      841 agaagatggg gtttttgatg atgaagatga agaggaagag aatatagaat caaaggtgac
      901 caagcctgtg caaattcaga agagagcagt caagagacca gcccctgcaa aaagcagtga
      961 tcattctgag gaggacagtg acctagagga aagcgatagt attgatgatg gagaggaact
     1021 ggctcagagt gataccagca ctgaggagca agaggataaa gctgtgcaag tctcaaacaa
     1081 aaagaagagg aaattaccct ctgatgtgaa tgaagggaaa actgttttta tcagaaatct
     1141 gtcctttgac tcagaagaag aagaacttgg ggagcttctc caacagtttg gagaactcaa
     1201 atatgtccgc attgtcttgc atccagacac agagcattct aaaggttgtg catttgccca
     1261 gttcatgact caagaagcag ctcagaaatg ccttctagct gcttctccag agaatgaggc
     1321 tggtgggctt aaactggatg gccggcagct caaggttgac ttggcggtga cccgtgatga
     1381 ggctgcaaag cttcagacga cgaaggtgaa gaagccgact ggcacccgga atctctatct
     1441 ggcccgagaa ggcttgattc gtgctgggac gaaggctgca gagggtgtga gtgctgctga
     1501 tatggccaaa agagaacggt ttgagctgct gaagcatcag aaactcaagg accagaatat
     1561 ctttgtctcc cgaaccaggc tctgcctgca caatctccca aaggctgtag atgacaaaca
     1621 gctcagaaag ctgctgctga gtgctactag tggagagaaa ggggtgcgca tcaaggagtg
     1681 tagagtgatg cgagacctca aaggagttca tgggaacatg aagggtcagt ccctgggcta
     1741 cgcctttgcg gagttccaag agcacgagca tgccctgaaa gccctccgcc tcatcaacaa
     1801 caatccagaa atctttgggc ctctgaagag accaatagtg gagttctctt tagaagatcg
     1861 aagaaaactt aaaatgaagg aattaaggat ccagcgcagc ttgcaaaaaa tgagatccaa
     1921 gcctgcaact ggtgagcctc agaaggggca accagagcct gcaaaagacc agcaacagaa
     1981 ggcagctcaa caccacacag aggaacaaag caaggtgccc ccagagcaga agagaaaggc
     2041 gggctctacc tcatggaccg ggttccagac caaggctgaa gtggagcagg tggagctgcc
     2101 tgatggaaag aagagaagaa aggtcctggc gctcccctca caccgaggcc ccaaaatcag
     2161 gttgcgggac aaaggcaaag tgaagcccgt ccatcccaaa aagccaaagc cacagataaa
     2221 ccagtggaag caggagaagc agcaattatc gtccgagcag gtatctagga aaaaagctaa
     2281 gggaaataag acggaaaccc gcttcaacca gctggtcgaa caatataagc agaaattatt
     2341 gggaccttct aaaggagcac ctcttgcaaa gaggagcaaa tggtttgata gttgatgatg
     2401 gcagcaggct gggtaagaag ctgggttgtg tactttctgg tgacactcct gggctcctcc
     2461 ccatcccccg tgtctctcac tgagggaaag aaaatcccca agggcactgc cactgtgctc
     2521 ggaggtgccc tggactgtgt acatctgaac tttggtccat cctttgatgt gtggttcgtt
     2581 agccacaaag agaaatatct gaaagtcaac atgatgcttc ttgcatatta tccagattat
     2641 tgtatgaagt tgtgtctata attattacca atttttattc tttatttctc aaatggaaac
     2701 acctgaaaaa gcattctgga gtgctgaatt tttaagatgt atattttgtt aagcatattc
     2761 tctaaatgag atattgtgtg gctttttagt aacaacgtca tttctaatat gtgtgactcc
     2821 tttattatgt atgaacattc tttgacattc ctaattcagc tctgtagtct tacacactgc
     2881 aggaactgtc taagcgagag cagagagaaa tgctttctaa cctaatcgct gcaggcggag
     2941 acacttggaa aagaatgggg ggaggtgggg cctgacagag agcagcactt atgtgtttgt
     3001 cagatgaggg gatttccagt tgaattggcc tgcagtggcc taaagacact agcctggtta
     3061 gcgatgacct gcatttctct catagagcac ctcccttttc atcgtatcca ctagctctct
     3121 aagtcctcct taatgaggac acttgatcct cattaagtct gccccttaag atggcttcac
     3181 acctactgaa aaactccagg ggtttgacat ctcactttga ttgaaatctt gtcttcctat
     3241 aacatttgat tccctgggct cttcagccct atcacctctg cttgtcttta tccactctct
     3301 tcttcattca cttttggcta cacaggcctt ccttccatct cttgactctt gaccacctca
     3361 gagcctttgt atccgttccc tttgcctgga gagtttttcc cttgcatctt ttacttgtca
     3421 ctcagatctc cactagttgt cgcctcctcc tggagctctt cccagactat ctaaagtagg
     3481 gcttttcttc ccctcccctc tatcttgccc ccttactgaa atctgcttcc ctgtttcttc
     3541 ttcttttttt tttttttttg agatggagtc tcactctgtc gcccaggctg gagtgcaatg
     3601 gcgctgtctc agctcattgc aacctccacc tcccgggttc aagcgacttt cccgcctcac
     3661 cctcccaagt agctgggact acaggtgcac gccaccattc ttggctaaat tttgtatttt
     3721 tagtagagat ggggtttcac catgttgact aggctggtct tgaactcctg acctcaggtg
     3781 atccgcccac ctcgacctcc caaagtcctg gtattacagg cgtgagccac cacgcctggc
     3841 ctgcttccct gtttctttct agcactaatc tctatctgaa atcatttgtc tctttctagc
     3901 actaatctct atctgaaatt gtttgtctct ccagttagaa tgtatgcttt gtgagaggga
     3961 ctttatccct cttgttcact cctgtagaca cagcacctag tactgaccca ggcacgtagt
     4021 aagtattgaa taaatatttg ttgaatgaaa aaaataaggt aggaaaggaa gaaacagtat
     4081 tcagtaggca agagaaaaag ttgagaacgt ggcccaaaat tcttgattgc ttagtctagt
     4141 tgagtgttac aaataatgct ttgacagaac cattgctgag ctagagatat ggttatttct
     4201 tttttttttt tttttttgag acagtcttgc tctgttgccc aggctggagt gcaatggcat
     4261 gatcttggct cactgcaacc tccgcctcct gggttcaagc gattctcctg cctcagcctc
     4321 ccgagtagcg gggattacag gtgctgccac cacgcccggc taatttttgt atttttagta
     4381 gagacgggtt ttcaccatgt tggccaggct gatctcaaac tcctgacctt gtgatctgcc
     4441 cacctcagcc tcctgaagtg ctgggattac aggcatgagc ctggttgaga catggttatt
     4501 tcatcgcaat atcttgggga acccatgaat gctctgaaat gcctttggtt tagaaatgga
     4561 tgaaggagag gccatggaaa tatttagacc ttttggagag atcgaaagga caggtgattt
     4621 atctccaagt tcacctcgag acatgacttg ggctgtcaaa tgttcttacg gtagcctggc
     4681 aacatgtctt tctcagcctg gtctgtacag tgtggaggaa gtaagggact ttattaagag
     4741 tgtcacaata gctataacct gccagtcagg tgatctgttt ttccttggcc atctctccgt
     4801 ctgctcacca ctcttttttc cctagtacac gaatatcttt aacattcaaa aatatatctt
     4861 aacacttagg atagatcaaa attggtgttc attcagataa cattgtcaga ttctcttaga
     4921 tccaaatatt tcttttaaca acttaacagt atgttaaaac ctcattcact tgcttggaga
     4981 gctgttgtac agttctttaa agagttcttt atatgaggtt gaatcttccc tttcttaata
     5041 gtcaaattct atatatggtg tcttcctttg gaacacctta ccatgggcta tttggtcagc
     5101 tccattgact ccttgccttg ggaattttag tgcagtgaga gttgtgctca cttctccttc
     5161 acttcagggc ctgatgtgtc aggaaatgga gttttctgaa ttaacatgaa agttgagttg
     5221 cagattgctt ggttaaaaaa caacaggtgg ggcacagagt ctcataccta tgattgcagc
     5281 acttcgggag gtgggaggat tgcttgaggt caggagtttg agaccgacct ggccaacata
     5341 gtgagacccc catctctatt attttgaaaa acaacagcaa attttttctt aacatccaag
     5401 acaaggccac cagtcaaaac tatcaagttt tagtagtatt ttcctgcttg attatataat
     5461 agcctggctt agagatacaa cctttaaata aggaatctta agatgatgtg cagctgttct
     5521 ttgccttatt tgtttgtttg ttggttagtt tgtagtttct aagaatctgc tctgttcagc
     5581 tgtacagttc cttcttctgg agttaacctg tggcaaggat tatgtttcac ctgtcacaaa
     5641 aatgagatct gtgccttcct ctattataaa gttagggcat gtgattcatt cttcgaaata
     5701 cttcaaaatg tactttggta tgtttttgtc ttgaaaagag gttttctagc tagaaattcg
     5761 gggcccagaa ggtcaaggct ccagagatcc ccttctcatc atccttcagt tgtctgagga
     5821 gacagaggat cacatgtgtc acagtgagtg ctgattcccc agaatctgca gtcttaagct
     5881 cccctgctga cgcacacagc cagttctctg cttcatattc atgtgaccca ctgtgaagtg
     5941 acaggcagct gccaattctg tcatataaga agcagctctg cccatgcaac tttgaaagtt
     6001 cctgcacttc tccatagact gctccttcat ggaaataaac acatcatcac actgtgggtg
     6061 cctaagctaa gtttgtttgc agtttgatga tgcccagctc cttttcaact cagccttaat
     6121 tggcacttta agggccagga tgaggtttct ctcaggccaa gtcgagattt ccagatttcc
     6181 ttttgtccaa ggctgaccag tttagaagtt attcacatcc ttgttttagt tctttccttc
     6241 ttgtcctggt acctcttcct ttccaggatt atttgcagag tctgtgatgg cttacttggt
     6301 gaccagacat ggggtgagct actggtatag tctgattact ttggcatcta ttctgaactg
     6361 gtcattggct gtacatgagt ttttgtgctg gtaaaggaat atactgggaa gattggaagg
     6421 cacagactgg gaactaattc tgagaagaga actgctgagt tactgaaaga ccttttggac
     6481 cacccctaaa tggagcatct tgatagatgg caaatccagt gtttcttaaa cttgtccatg
     6541 ctgcccagag cccactgcct tttatcagat gtgagacttc actgccacag tgtcatccca
     6601 cagtttcctt ccctggacat ttgataaagg gaaaatcatt tcttgtcctt taaggcaggg
     6661 actattattt tttcactttt ccacataccc cacaacacct aacattgatt tactcgtagt
     6721 aggagtttca tactgttgaa ctctctaaag gccatttgtt ccagggccta gctgggcttg
     6781 tgaaggacaa cagagtcatt tcctaaggac cccaaaagac agcatgaagg aaaaaataat
     6841 aataaactgc tgttcacagt gccttgagtg taccaccgta ctttctgcta tgccttgtcc
     6901 attccaatct ggacagtctc tgtgcccctc ctttccactc aagtgttatc cagcactcaa
     6961 gttctggctc aaggcccaac atctccgtgg ggacctcagc catcccaggg cattgtgacc
     7021 ccttcctcta agtccccggc acactcgctg attggtaccc tctcattcga caaagcatat
     7081 gccattgtgg cttacttgtc atttctttag gtcttgcctt cccaagtaga tcatgagcca
     7141 ctataagaac tagctcccat agtcccagcc cctgggcctg gtacatggca atgcttagtg
     7201 attggtgatt gaggataatg gtggtaaagg atgtaccaga cagtcatctc ctgaagagat
     7261 gccgaacaac ctgtccttgt tttatgtatt ttctctttct ttcctgtcca gttttattcc
     7321 tctcatagta actgctaaaa aaatatcagt tcctgtcact cttccacccc ttttctccct
     7381 ctcccctgca ttgtggtctg ggccttggtc cactagcaac tccccttagg tgttgcttaa
     7441 tctgcctcat ggccaaagcc aatcccattc ctgtcccccg ctacccaagg gactcccagt
     7501 ctgtatgcac aaggcgggat gtgaagtctg gatgtgcaag aaacccagct gtaagaaaca
     7561 gcttccctcg gcttggcatg gtggctcatg cctatattcc cagcactttg agaggtcaaa
     7621 gtgggagaat cacttgagcc caggagttca ggactagcct gggcaacata gcaagatccc
     7681 acctctacaa aaaaagaaaa aattcagagt ctcaaatgtc ccttcatctc cttactctcg
     7741 acctgtctcc ctagttctct gccgcctttt cctctcccct ggatctgaca ctcaattgtc
     7801 tgcatgcact tttcaactga aagagactcc aatgccatcc ttctgatgaa atttttgctt
     7861 tggatactac tgcagaaaaa atgctatctt gtattctggt ccatggtggg gaagaccctg
     7921 tcgtagaacc tggcaactca agtggaggga ggggccagaa cattgttctt atgctattta
     7981 cagtgagaca acaggattga tgcagaactt tctttttttt tttttttttt tgagacagag
     8041 tttcattctt gttgcccagg gctggagtgc agtggcatga tctcagctca ctgcaacctc
     8101 caccccccag gttcaagcag ttcttcctca gcctccggag tagctgggat tacaggcgtg
     8161 cgccaccacg ccccactaat ttttgtattt ttggtagaga cggggtttca ccagtgttgg
     8221 ccaggctggt ctcgaactcc tgacctcagg tgatccaccc acctcggcct cccaaagtgc
     8281 tgggattaca ggcatgaacc accgtgcccg gccgtgatgc gcaactttct aataacatac
     8341 ttttgaaagt gcccagacat acatccctcc tctggtacca cagtggccat cagttgccag
     8401 agaacatgaa attatccagc cctcagctct gcagcaggat tctgaggagt aaagcaggcc
     8461 tgtaaagtac tctaaagtac ttcagagagg taatgccaca aagcgaagaa cacctcttgg
     8521 aggcagagcc cctcagccct atccaggcca gcagtgtcca cttgaaatct gaaagcagcc
     8581 tccctcacca aaccagcaag atggaaaacc tccctgggtt ggcaagtggc cctgggaagt
     8641 acatgcccca tctctgtcag gatagcagtg gagaggtttc gtgccagtgc cagctccacc
     8701 cacccagatg gtactcaaga ctccaagcct gtcaatgggg tggaaacttt ctggcatttt
     8761 ctgtcagaag ggtgagttag cactgaacca tctcatgtgt cttttcactg agtaacagcc
     8821 catatccatt ccatgaaatg agtgactgct ttgttgaatc agatagtaac aaacatttat
     8881 ttgtagtctg gttgtgtcat atcatggttg aattgcaaac aggttggata gaagagtcag
     8941 caaaaatcaa caaaagcatt ctgtaaaaaa cttttctaga attacaataa atggcattgt
     9001 atattttatt tataaattat gtgctgcaca tcatttttat caatgaaatt tataataaat
     9061 ttctgtacat atatacattt ttatcccaga gagccagttg ttaagcattt accagcaata
     9121 aatgcttttt gtttcctgct tacacaggtt ctgggagtgg ccagcccact ctttgagatg
     9181 tccccacttg cttttttagt tgtccaagta gtgttctgcc cagccttccc gactctcttt
     9241 cttatccttc cctcgaaact attctgttcc ttatgcttaa atactttcca gtcatgggag
     9301 ctttgctgta ggcccttggc ctttcatggg tagcttctga tacgtgcatg ggtgttaata
     9361 gaggaagttg accccgcctg ggaagaataa tgacctatgg agacctggcc ctttctctta
     9421 tggcttctta aagtgacagc tgttatggga agttcaggca tcttgacgtg gaaaatacat
     9481 tgttcatttt cttttaattt tttttcccct aaccactata ccaacaggga tggaaagata
     9541 cttttagttg gaaggaattt ggagccctta aacgacacct ggagcagctg cctgtgggtg
     9601 gggctttgca cagtctcatc ctggcaaggg aggacgagcc aaggaccagt tttgcagaat
     9661 tgtcatcatg aggccctggt tgtgtgctgg gctggggcat tgcccctttc caggaggcca
     9721 ggccaagcag ggctgcctgg cttaggcttt tgcatcttca gcatcctttc acgtctctta
     9781 tctcaggtga ccttcacagc aagcctggtg aaggttattg agaagcagat gtcaccacct
     9841 agtcttagag ctgatgaaag caggatgtgg ggaagtccag accctctcct gaaacccctt
     9901 ggccacctga gctagtacca gagcaaggtc ccacttggcc gtgagtgctg tctctagggc
     9961 ctatttcagg aactgtctca tatataagaa cagaacactt tttgccagct ataccaaatg
    10021 tttttgggat taaaaaaata gtttctcttt tccaaattag gtggtaagaa aaggaagggc
    10081 attttcattc tcacattctt tgaatgttga aacgttttaa aaacttccag ctgggcttgg
    10141 tggctcatac ctgtaacccc agcactatgg gaggctgaga tgggaggatc ccttgaggcc
    10201 aggagttcag gaccagcctg ggcaacatag taaaactgcc caaaatttga aaattagcct
    10261 tgtgtggtgg tgtgcactgt agtcccagct gctcgggagg ctggggcagg aggattgctt
    10321 gagcccagga gtttgaggct gcagtgagct atggttgtac cactgtactc caacctgggc
    10381 aacagcgtga taccctgtct aaaaaaataa taaaaataaa aaaggattaa accctttact
    10441 tgaccagctt cttttcctgc tacccctgga ctaactaatc attacatatt tttgtagttg
    10501 ttttttcttt ctttctctct cctgatctac cacaagccaa atgtactcat atacatacta
    10561 ataggtgaaa aaagagagtc tgaggagtga atacatttat tttgtgattt cctaggcagt
    10621 agctaggact cccttagagg ttgctaatag ggaaagggtg cgctggctct actcagtttt
    10681 ataactgctt ttccccgaat tctgcagaca tcttcattcc cctggaggtc agataatggc
    10741 tatttatttt ccatagccat gaaaatctct ggggagagct gtggcaattt gacgagagct
    10801 attaaaggga cattaggatt gaagtagctg ctcaggcagt cacataccct cgatcctcat
    10861 ctgcagggac agctgccaga acgaatgagc ccagctctcc tgcccgcagc cagccgcgtg
    10921 tgggtgcaac tggcgaccag ccactggagt gagtcccagg gaaggggaca ggttcttaga
    10981 atcaccattt gtctctgctc tctccctctc tgcaatagga cgggcactct aaactcacat
    11041 aatggttaat aacaacagct aacaattact gagcacctac tatgtgtcag gcatgtgctg
    11101 aggatgatcg catcaagtaa aatgcctgtc tctggcccag aggcccagaa gaagagaaag
    11161 aagggaaatc tgtaggaggc aaacagtccc ttacccctct gcttgcagac cttcagtgac
    11221 aggacactcc ctgtttgctc caagcacctc ttgcattttc agagcttggg acacagattc
    11281 agggacttgc acttcgatag agtgcctcag gacccctcgt cggagccatg gaaagtcagt
    11341 ttctgggccc atccttcctg tgggggtgtc tttccttctc ttggccaccc cctaggaatc
    11401 cctagtagag agcaggcact taatagccag tgcagtgaga gtggtctgtg atgtctgggc
    11461 cagggcaagg cccgccaagt gggctcccag gtgcctgcca cagagcctct ggggtttgag
    11521 gccctcagtg acccttaggc aatagctggg tcttaatgag ggatcatgtc ctttcctggg
    11581 tagtcgtggg tagaggggtg tgaactgatc tgagctactc taggaaggct agagacaaaa
    11641 gcaggaacca agagaagggc tgaggctcct tccaagagac tccaagtcct gagggcaaga
    11701 agcggagagc cttgtgccag gccaggtgtt gcccctgtca gtgctgacgg acaggcaaga
    11761 gaggctgctg atgctgcagc cctgtgaagc tgagactcac cctttgccca ctttcacagc
    11821 catctcccca ggaggctgtg gtgacacagg taaaagccaa aggacagagg atgaccctgg
    11881 acaaatcact cagaccctcc agtcctcttt gctcatttat aaaatacagg caaaaagccc
    11941 cctagtacta aatgaaatag ccactgtaaa agagcacggg agatagggtc tgtgatgtct
    12001 tttgtcccca gtgtcctgag tgaattcaca ggaaagggga gaaagactgg ttgcccactt
    12061 ccagggtgat tggctaattt ccacttcttt cctgctaggg atgggaacac acgccagaat
    12121 cctgggaagg ctacatgtcc tcaggtggtg ctggccccac ctccagcctc tgcagggata
    12181 ccaggatatg agccaggctc tgctcccggg gtgacccatc ctcctcagtg ccccttcttt
    12241 cctcacaact gcaggcagaa ggagagtgtg tcctgtctct ctgaggagct ggctgtgcca
    12301 tttaagcagg ccctaggggt ggagcgctgt gaagagatgg cacccaggtc cctgttcctc
    12361 cttttccaga gcaaacactg ctaagggatc atgacagtcc ctgcatctgg cccagactgg
    12421 gccttgggag gcttttgaca tcaatccatg caaccgcacc caacaattgg agtcagcatg
    12481 ggaggtgaga cccacttgcc aattttgctc tcagggaaca gccctcttta ctaaaacata
    12541 gcacagtatt gataacagtt gtttccaggc atcgtagaaa gcgtttagtg ggcattaacg
    12601 tctttgatcc tcaccacaag gtcaggggtt ggatgatgtt agcatgctca ttgaaggatc
    12661 agaaaagtca ggctcaagat agctcgccct tcattcagcc agccggtgtt aactgaatat
    12721 taactgtgca cccgtctgtg ccagtgttcc cccaggagct gcagagggtc ctgagcagag
    12781 tgagctcaag ccacttggga gctcacattc cagctatcag tgctgattca tctcaaatgt
    12841 ttgatccacg ctgggttcta acccttccct gctcagagcc ctcagagtcc aggtcaggta
    12901 gaacccagaa cagagcctct ggcaggaagg agcttgcatg gtcctcaggc ttcatgtcca
    12961 gagatcattc ctccactttg agcttctttg tgaaaaccaa tcacaaagag aggaggggtg
    13021 aaatgtgcca aagcctctgc cagggttgta gcaaggaaac ctgggcttct agggaaagtt
    13081 gagaaagggc ctatattagt caggagggct actgtaagag agtaccacag gctgggtggc
    13141 ttaaacaaca gaaatttatc accttacggt tctggaggct agaagtctaa aatcaaagtg
    13201 ttggcaaggt tggttccttc atgaggaatt tcttggcgtt gcctggcata tagatgcatc
    13261 actgcagtct ctgcctcgtt gtcacatggc catcttctcc ctgtgtctat aggtctatgt
    13321 ccaaatttcc ctcttcttat aaagacacca gtcatattgg cttaggccca gcccaatgat
    13381 ttcatcttaa tttgattaca tctctgctat ggtttgaatg tgtcccttcc aaaattcagg
    13441 ttattgccaa tgtgatagta ttgagatggg gtccttaaag aagtaattag gccatgaggg
    13501 tgcctctctc tgaagggagg ctcattggat tgtatcagtg taacataatt tacataacca
    13561 gttctttatg tgatggaaat cccattcaac ggtttccaac ctttgctatt acaaactgct
    13621 gtgaagagaa acatatgtca ttatactaat caggtgctgt tgttgttttt ataatgcatt
    13681 atcctggaga gactgcccct cccagggcta gctactttgg ggagagagta aacaacttgg
    13741 tcgagcgtgc ctttcgtatg caaaccagtc aatccagagc ccacaccccc agtcacctcc
    13801 tttatcaaac tctgacacag caagccaata ttccccctgc cctaaatcac tccagggcca
    13861 ggcatgggac aactagggac aatccctata gccagggcct gccaaagtta tacagattag
    13921 ccaatcctaa gcctgcttcc ctgccttgcc ttgcctttct gctggaaact acattaaagg
    13981 cgctggatcg tgcttttccc tcaccccctc tgcttcttgg ctgacccaag ttcttcctgt
    14041 gtggccctgc aaggcgtgac acacctctcc tcctgggaac tgcataacaa actcttcttg
    14101 cagagatagt tttctctgtg tctgtcatct taccatacct gatgaaaaca aatatgggta
    14161 catttttttt tttttttgag agagagggtc tcactctgtc tcccaggctg gagtgcagtg
    14221 gtgtaatcac aggtcactgc agcctcgacc tcctgggctc tagtgatcct cccacgtcag
    14281 ccttgcaaat agctgagact acaggcacac accaccatgc ctagctaatt tttggtgtat
    14341 ttgttataga gacagagttt cgctatgttg cccaggctgg tctcaaactc ctgagctcaa
    14401 gtgatccacc caccttagcc tctcaaagtg ctgggattat aagtgtgagc cacagcatcc
    14461 agccatgggt acattttaaa gcaggcgttt tgttcatgtg cagcccttgt tctcagttaa
    14521 ggggaaaatg agtgatcctt tgcttggctc tgaaggagca gtgttttata tgtaaagaat
    14581 atattctgta tatttaaaga agagcaatgg ggggcatttg aaaataaatc cgttcatttt
    14641 tttctgattg taaaaataat atatgctcag taaagagaat ctgaaaaata cagaagtatt
    14701 gggggaaccc acccccaata tttcaacata ggttctttct attttccata agtgtcggcc
    14761 gactgagaaa taaagagaaa tagtacaaag agaggaattt taacagctgg gctgccgggg
    14821 gtgacgtcgc atatcagtag gactgtgatg cccacctgag cctcaaacca gcaagttttt
    14881 tattaagggt ttcaaaaggg gagggggtgt aaaacaggga gtaggtacaa agatcacatg
    14941 cttcaaaggg caaaagcaga acaaagatca catgcttctg aggaaacaag acaaaaggca
    15001 aaacagaact actgataagg gtctatgttc aactgtgcgc gtattgtctt ttttttttat
    15061 tatttaagtt ttagggtaca tgtgcacact gtgcaggtta gttacatatg tatacatgtg
    15121 acatgctggt cgctgcaccc actaactcgt catctagcat taggtatatc tcccaatgct
    15181 atccctcccc cctcccccca cccctcaata gtccccagag tgtgatgttc cccttcctgt
    15241 gtccatgtgt tctcattgtt caattcccac ctatgagtga gaatatgcgg tgtttggttt
    15301 tttgttcttg cgatagttta ctgagaatga tgattttcaa tttcatccgt gtccctacaa
    15361 aggacatgaa ctcatcattt tttatggctg catatgtgta tatgtgccac attttcttaa
    15421 tccagtctat cattgttgga catttgggtt ggttccaagt ctttgctatt gtgaatagtg
    15481 ccgcaataaa catacgtgtg tgtgtgt
//
