LOCUS       NM_001258392            9963 bp    mRNA    linear   PRI 04-OCT-2024
DEFINITION  Homo sapiens ClpB family mitochondrial disaggregase (CLPB),
            transcript variant 2, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_001258392
VERSION     NM_001258392.3
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 9963)
  AUTHORS   Baker,M.J., Blau,K.U., Anderson,A.J., Palmer,C.S., Fielden,L.F.,
            Crameri,J.J., Milenkovic,D., Thorburn,D.R., Frazier,A.E., Langer,T.
            and Stojanovski,D.
  TITLE     CLPB disaggregase dysfunction impacts the functional integrity of
            the proteolytic SPY complex
  JOURNAL   J Cell Biol 223 (3) (2024)
   PUBMED   38270563
  REMARK    GeneRIF: CLPB disaggregase dysfunction impacts the functional
            integrity of the proteolytic SPY complex.
REFERENCE   2  (bases 1 to 9963)
  AUTHORS   Wu,D., Liu,Y., Dai,Y., Wang,G., Lu,G., Chen,Y., Li,N., Lin,J. and
            Gao,N.
  TITLE     Comprehensive structural characterization of the human AAA+
            disaggregase CLPB in the apo- and substrate-bound states reveals a
            unique mode of action driven by oligomerization
  JOURNAL   PLoS Biol 21 (2), e3001987 (2023)
   PUBMED   36745679
  REMARK    GeneRIF: Comprehensive structural characterization of the human
            AAA+ disaggregase CLPB in the apo- and substrate-bound states
            reveals a unique mode of action driven by oligomerization.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 9963)
  AUTHORS   Tucker,E.J., Baker,M.J., Hock,D.H., Warren,J.T., Jaillard,S.,
            Bell,K.M., Sreenivasan,R., Bakhshalizadeh,S., Hanna,C.A.,
            Caruana,N.J., Wortmann,S.B., Rahman,S., Pitceathly,R.D.S.,
            Donadieu,J., Alimi,A., Launay,V., Coppo,P., Christin-Maitre,S.,
            Robevska,G., van den Bergen,J., Kline,B.L., Ayers,K.L.,
            Stewart,P.N., Stroud,D.A., Stojanovski,D. and Sinclair,A.H.
  TITLE     Premature Ovarian Insufficiency in CLPB Deficiency: Transcriptomic,
            Proteomic and Phenotypic Insights
  JOURNAL   J Clin Endocrinol Metab 107 (12), 3328-3340 (2022)
   PUBMED   36074910
  REMARK    GeneRIF: Premature Ovarian Insufficiency in CLPB Deficiency:
            Transcriptomic, Proteomic and Phenotypic Insights.
REFERENCE   4  (bases 1 to 9963)
  AUTHORS   Capo-Chichi,J.M., Boissel,S., Brustein,E., Pickles,S.,
            Fallet-Bianco,C., Nassif,C., Patry,L., Dobrzeniecka,S., Liao,M.,
            Labuda,D., Samuels,M.E., Hamdan,F.F., Vande Velde,C., Rouleau,G.A.,
            Drapeau,P. and Michaud,J.L.
  TITLE     Disruption of CLPB is associated with congenital microcephaly,
            severe encephalopathy and 3-methylglutaconic aciduria
  JOURNAL   J Med Genet 52 (5), 303-311 (2015)
   PUBMED   25650066
  REMARK    GeneRIF: Disruption of CLPB is associated with congenital
            microcephaly, severe encephalopathy and 3-methylglutaconic aciduria
REFERENCE   5  (bases 1 to 9963)
  AUTHORS   Saunders,C., Smith,L., Wibrand,F., Ravn,K., Bross,P., Thiffault,I.,
            Christensen,M., Atherton,A., Farrow,E., Miller,N., Kingsmore,S.F.
            and Ostergaard,E.
  TITLE     CLPB variants associated with autosomal-recessive mitochondrial
            disorder with cataract, neutropenia, epilepsy, and methylglutaconic
            aciduria
  JOURNAL   Am J Hum Genet 96 (2), 258-265 (2015)
   PUBMED   25597511
  REMARK    GeneRIF: CLPB is proposed to function as a mitochondrial chaperone
            involved in disaggregation of misfolded proteins, resulting from
            stress such as heat denaturation.
REFERENCE   6  (bases 1 to 9963)
  AUTHORS   Wortmann,S.B., Zietkiewicz,S., Kousi,M., Szklarczyk,R., Haack,T.B.,
            Gersting,S.W., Muntau,A.C., Rakovic,A., Renkema,G.H.,
            Rodenburg,R.J., Strom,T.M., Meitinger,T., Rubio-Gozalbo,M.E.,
            Chrusciel,E., Distelmaier,F., Golzio,C., Jansen,J.H., van
            Karnebeek,C., Lillquist,Y., Lucke,T., Ounap,K., Zordania,R.,
            Yaplito-Lee,J., van Bokhoven,H., Spelbrink,J.N., Vaz,F.M.,
            Pras-Raves,M., Ploski,R., Pronicka,E., Klein,C., Willemsen,M.A., de
            Brouwer,A.P., Prokisch,H., Katsanis,N. and Wevers,R.A.
  TITLE     CLPB mutations cause 3-methylglutaconic aciduria, progressive brain
            atrophy, intellectual disability, congenital neutropenia,
            cataracts, movement disorder
  JOURNAL   Am J Hum Genet 96 (2), 245-257 (2015)
   PUBMED   25597510
  REMARK    GeneRIF: Mutations in CLPB define a syndrome with intellectual
            disability, congenital neutropenia, progressive brain atrophy,
            movement disorder, cataracts, and 3-methylglutaconic aciduria.
REFERENCE   7  (bases 1 to 9963)
  AUTHORS   Acebron,S.P., Martin,I., del Castillo,U., Moro,F. and Muga,A.
  TITLE     DnaK-mediated association of ClpB to protein aggregates. A
            bichaperone network at the aggregate surface
  JOURNAL   FEBS Lett 583 (18), 2991-2996 (2009)
   PUBMED   19698713
  REMARK    GeneRIF: formation of the DnaK-ClpB bichaperone network is a three
            step process
            Erratum:[FEBS Lett. 2009 Oct 6;583(19):3301]
REFERENCE   8  (bases 1 to 9963)
  AUTHORS   Haslberger,T., Zdanowicz,A., Brand,I., Kirstein,J., Turgay,K.,
            Mogk,A. and Bukau,B.
  TITLE     Protein disaggregation by the AAA+ chaperone ClpB involves partial
            threading of looped polypeptide segments
  JOURNAL   Nat Struct Mol Biol 15 (6), 641-650 (2008)
   PUBMED   18488042
  REMARK    GeneRIF: ClpB-DnaK reactivated all aggregated fusion proteins with
            similar efficiency, without unfolding native domains, demonstrating
            that partial threading of the misfolded moiety is sufficient to
            solubilize aggregates.
REFERENCE   9  (bases 1 to 9963)
  AUTHORS   Perier,F., Radeke,C.M., Raab-Graham,K.F. and Vandenberg,C.A.
  TITLE     Expression of a putative ATPase suppresses the growth defect of a
            yeast potassium transport mutant: identification of a mammalian
            member of the Clp/HSP104 family
  JOURNAL   Gene 152 (2), 157-163 (1995)
   PUBMED   7835694
REFERENCE   10 (bases 1 to 9963)
  AUTHORS   Wortmann,S.B. and Wevers,R.A.
  TITLE     CLPB Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   27891836
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DC396265.1, BU848809.1,
            AK023214.1 and AP000593.4.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Dec 18, 2018 this sequence version replaced NM_001258392.2.
            
            Summary: This gene belongs to the ATP-ases associated with diverse
            cellular activities (AAA+) superfamily. Members of this superfamily
            form ring-shaped homo-hexamers and have highly conserved ATPase
            domains that are involved in various processes including DNA
            replication, protein degradation and reactivation of misfolded
            proteins. All members of this family hydrolyze ATP through their
            AAA+ domains and use the energy generated through ATP hydrolysis to
            exert mechanical force on their substrates. In addition to an AAA+
            domain, the protein encoded by this gene contains a C-terminal D2
            domain, which is characteristic of the AAA+ subfamily of
            Caseinolytic peptidases to which this protein belongs. It
            cooperates with Hsp70 in the disaggregation of protein aggregates.
            Allelic variants of this gene are associated with
            3-methylglutaconic aciduria, which causes cataracts and
            neutropenia. Alternative splicing results in multiple transcript
            variants. [provided by RefSeq, Apr 2015].
            
            Transcript Variant: This variant (2) lacks an in-frame exon in the
            5' coding region compared to variant 1. The encoded isoform (2) is
            shorter than isoform 1.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript 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 :: AK023214.1, SRR14038197.1195797.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000350]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000538039.6/
                                                  ENSP00000441518.1
            RefSeq Select criteria             :: based on manual assertion,
                                                  conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1                 DC396265.1         150-150
            2-702               BU848809.1         1-701
            703-2282            AK023214.1         706-2285
            2283-9963           AP000593.4         74355-82035         c
FEATURES             Location/Qualifiers
     source          1..9963
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q13.4"
     gene            1..9963
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /note="ClpB family mitochondrial disaggregase"
                     /db_xref="GeneID:81570"
                     /db_xref="HGNC:HGNC:30664"
                     /db_xref="MIM:616254"
     exon            1..460
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     CDS             58..2091
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /EC_number="3.6.1.3"
                     /note="isoform 2 is encoded by transcript variant 2;
                     suppressor of potassium transport defect 3; testicular
                     secretory protein Li 11; caseinolytic peptidase B protein
                     homolog; ClpB caseinolytic peptidase B homolog;
                     ankyrin-repeat containing bacterial clp fusion; ClpB
                     homolog, mitochondrial AAA ATPase chaperonin; caseinolytic
                     mitochondrial matrix peptidase chaperone subunit B;
                     mitochondrial disaggregase"
                     /codon_start=1
                     /product="mitochondrial disaggregase isoform 2"
                     /protein_id="NP_001245321.1"
                     /db_xref="CCDS:CCDS58154.1"
                     /db_xref="GeneID:81570"
                     /db_xref="HGNC:HGNC:30664"
                     /db_xref="MIM:616254"
                     /translation="MLGSLVLRRKALAPRLLLRLLRSPTLRGHGGASGRNVTTGSLGE
                     PQWLRVATGGRPGTSPALFSGRGAATGGRQGGRFDTKCLAAATWGRLPGPEETLPGQD
                     SWNGVPSRAGLGMCALAAALVVHCYSKSPSNKDAALLEAARANNMQEVSRLLSEGADV
                     NAKHRLGWTALMVAAINRNNSVVQVLLAAGADPNLGDDFSSVYKTAKEQGIHSLEVLI
                     TREDDFNNRLNNRASFKGCTALHYAVLADDYRTVKELLDGGANPLQRNEMGHTPLDYA
                     REGEVMKLLRTSEAKYQEKQRKREAEERRRFPLEQRLKEHIIGQESAIATVGAAIRRK
                     ENGWYDEEHPLVFLFLGSSGIGKTELAKQTAKYMHKDAKKGFIRLDMSEFQERHEVAK
                     FIGSPPGYVGHEEGGQLTKKLKQCPNAVVLFDEVDKAHPDVLTIMLQLFDEGRLTDGK
                     GKTIDCKDAIFIMTSNVASDEIAQHALQLRQEALEMSRNRIAENLGDVQISDKITISK
                     NFKENVIRPILKAHFRRDEFLGRINEIVYFLPFCHSELIQLVNKELNFWAKRAKQRHN
                     ITLLWDREVADVLVDGYNVHYGARSIKHEVERRVVNQLAAAYEQDLLPGGCTLRITVE
                     DSDKQLLKSPELPSPQAEKRLPKLRLEIIDKDSKTRRLDIRAPLHPEKVCNTI"
     exon            461..512
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            513..599
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            600..703
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            704..832
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            833..930
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            931..1045
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            1046..1123
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            1124..1179
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            1180..1224
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            1225..1386
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            1387..1543
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            1544..1617
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            1618..1737
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            1738..1842
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     exon            1843..9963
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2128..2133
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /note="hexamer: AATAAA"
     polyA_site      2157
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /note="major polyA site"
     polyA_site      5004
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
     regulatory      9542..9547
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /note="hexamer: AATAAA"
     polyA_site      9564
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
     regulatory      9944..9949
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
                     /note="hexamer: AATAAA"
     polyA_site      9963
                     /gene="CLPB"
                     /gene_synonym="ANKCLB; ANKCLP; HSP78; MEGCANN; MGCA7;
                     MGCA7A; SCN9; SKD3"
ORIGIN      
        1 gttggacgtg gtcagcacag gggccggcac cacggggtta tcgaagcagc tgtcaagatg
       61 ctggggtccc tggtgttgag gagaaaagca ctggcgccac ggctactcct ccggctgctc
      121 aggtccccaa cgctccgggg ccatggaggt gcttccggcc ggaatgtgac tactgggagt
      181 ctcggggagc cgcagtggct gagggtagcc accggggggc gccctggaac atcgccggcc
      241 ttgttctccg gacgtggggc agccaccggg gggcgccagg gaggacgctt cgataccaaa
      301 tgcctcgcgg ctgccacttg gggacgcctt cctggtcccg aagaaacact cccaggacag
      361 gacagctgga acggggtccc cagcagggcc ggactgggca tgtgcgccct ggccgcagcg
      421 ctggtggttc attgctacag caagagtccg tccaacaagg atgcagccct gttggaagct
      481 gcccgtgcca acaatatgca agaagtcagc aggctgttgt cagaaggtgc agatgtcaat
      541 gcaaagcaca gacttggctg gacagcactc atggtggcag ccatcaaccg aaacaacagt
      601 gtggtacagg tcctgcttgc tgctggggct gatccaaacc ttggagatga tttcagcagt
      661 gtttacaaga ctgccaagga acagggaatc cattctttgg aagtcctgat cacccgagag
      721 gatgacttca acaacaggct gaacaaccgc gccagtttca agggctgcac ggccttgcac
      781 tatgctgttc ttgctgatga ctaccgcact gtcaaggagc tgcttgatgg aggagccaac
      841 cccctgcaga ggaatgaaat gggacacaca cccttggatt atgcccgaga aggggaagtg
      901 atgaagcttc tgaggacttc tgaagccaag taccaagaga agcagcggaa gcgtgaggct
      961 gaggagcggc gccgcttccc cctggagcag cgactaaagg agcacatcat tggccaggag
     1021 agcgccatcg ccacagtggg tgctgcgatc cggaggaagg agaatggctg gtacgatgaa
     1081 gaacaccctc tggtcttcct cttcttggga tcatctggaa taggaaaaac agagctggcc
     1141 aagcagacag ccaaatatat gcacaaagat gctaaaaagg gcttcatcag gctggacatg
     1201 tccgagttcc aggagcgaca cgaggtggcc aagtttattg ggtctccacc aggctacgtt
     1261 ggccatgagg agggtggcca gctgaccaag aagttgaagc agtgccccaa tgctgtggtg
     1321 ctctttgatg aagtagacaa ggcccatcca gatgtgctca ccatcatgct gcagctgttt
     1381 gatgagggcc ggctgacaga tggaaaaggg aagaccattg attgcaagga cgccatcttc
     1441 atcatgacct ccaatgtggc cagcgacgag atcgcacagc acgcgctgca gctgaggcag
     1501 gaagctttgg agatgagccg taaccgtatt gccgaaaacc tgggggatgt ccagataagt
     1561 gacaagatca ccatctcaaa gaacttcaag gagaatgtga ttcgccctat cctgaaagct
     1621 cacttccgga gggatgagtt tctgggacgg atcaatgaga tcgtctactt cctccccttc
     1681 tgccactcgg agctcatcca actcgtcaac aaggaactaa acttctgggc caagagagcc
     1741 aagcaaaggc acaacatcac gctgctctgg gaccgcgagg tggcagatgt gctggtcgac
     1801 ggctacaatg tgcactatgg cgcccgctcc atcaaacatg aggtagaacg ccgtgtggtg
     1861 aaccagctgg cagcagccta tgagcaggac ctgctgccag ggggctgtac tttgcgcatc
     1921 acggtggagg actcagacaa gcagctactc aaaagcccag aactgccctc accccaggct
     1981 gagaagcgcc tccccaagct gcgtctggag atcatcgaca aggacagcaa gactcgcaga
     2041 ctggacatcc gggcaccact gcaccctgag aaggtgtgca acaccatcta gcagccacct
     2101 gcctgctcct atgtgccctc accatccaat aaaggcccct tggctgtggc atggcaactg
     2161 acttaccttc ccctcatgcc gctcccatct ctacccagtc tcaggcctgc ttacctcctc
     2221 acagcccatg aagacccctt ctcagcccca aaacctgaag gaggaatttc gccctactct
     2281 ggcccctttg ttgtgggccc ataacctgct aacaagcctt caggagagga gctgcctttc
     2341 cacccccttc aaggcaagga gggatggagg tcccttattt ccttcagaat gatccccatc
     2401 ccccatagtc gccagacttt ctcatgttcc caggaagctc agaagtatgg cagctaagaa
     2461 cacagctggc tggaagaaga cagggaccag actgaactgc caccctctgc tagtcctcat
     2521 gcaactcagt ccccagaatg gctccactgg gagtggagga agagctcaga ggcccaggtg
     2581 cagatagttc tgcaatttag tctgtagcct cctcgttccc taccctaaaa ttctaagggg
     2641 aagggaccca tagaggcttg cctgtttccg ctactatatt atgcccagtg ttcctcctca
     2701 ccccacgtcc tggggtcagg ccagaccatg tttcgtcagc cttggggact aggccagtgt
     2761 tgggcacctc caggaggagg cctgactggt tcattaccct cccctactca gactgagcag
     2821 cagtcccaga taaccaagca agctcagctc tgtgggggcc tccttcaaaa gaccaacatc
     2881 gcagacatta ggaagctgta ggaagagaga tcatgggttt gacctctgcc cacatggcca
     2941 tggagtcagc ctcagccctg tctgtactgc tcgtccagct aaacgagcct ggaataaaca
     3001 tgcagtttat tcagtctgca tgttagtcac aaagcagagg gtctggacac cgtcccccaa
     3061 gggcatttca cagaccagcc aatgtttcaa gcccacctta gccaggcaca gtaaggcctg
     3121 gtgcatcctt gggcaccatc tacagtagcc actgctgata agcagtccac ccaccttccc
     3181 ccacaggccc ttcatggaac cctcgcgtag tgttagctag tctttcagga agcagagaat
     3241 ggggccagga atcaaagtcc cttgggtaat ggaagcatgt cctaacagta tggtgggtat
     3301 gaggcagtca gaatccaggg tgtgagctcc agcagatgct tggatcactg tctacccctc
     3361 aggggctgct gctccctacc tcactgactg cctttttttt tttttttttt tttttgagac
     3421 agagtctcac tctgtccccc aagctggagt gcagtggcgc gatctcggct cactgcaagc
     3481 cctgcctccc aggttcacgc cattctcctg cctcagcctc ccgagtagct gggactacag
     3541 gtgcccacca ccacgcccgg ctaccttttt gtatttttag tagagacagg gtttcaccat
     3601 gttagccagg atggtctcaa tctcctgacc ttgtgatctg cctgcctcgg cctcccaaag
     3661 tgctgggatt acaggcatga gccactggac ccggcctgct tttcattgtt ttttactttt
     3721 tgttttgaaa taattttaga cttagagaaa gttgcagaaa tagtagaaaa ttcccatgta
     3781 tctttcatct agcatctccc aatgattaca tcctacaaag ccatactgta gtttatcaaa
     3841 accaggaaat tgccgggtgt ggtggctcat gcctgtaatt ccagcacttt gggaggctga
     3901 ggcaggcaga ttacctgagg tcaggagttc gagaccagcc tggccaacat ggtgaaaccc
     3961 tgtctgtact aaaaatacaa aaattagcca ggcccgctgg tgcccacctg taatcccagc
     4021 tacttgggag gctgaggcag gagaatcact tgagcccagg aggcggaggt tgcagtgagc
     4081 tgaaatcacg ccactgcact ccagcctggg cgacagagtg agactccgtc tcaaaaaaag
     4141 aaaaccagga agttaacatt gataaactac tactaactaa tctacggaca ttcaaatttt
     4201 gccagttttc ccgatgatgt cctttgtctg gtccagggtc ccatattgca ttttgttgtg
     4261 gtgtttcctt catctctgtc agcctgtgac agtttcttgg tctttatctt tcatgacctt
     4321 gacactttgg aagagtccag gccagttatt ttatagaata ttccccagtt ttagtttgtt
     4381 taatgttttt acatgatatg attgaggatc tgcatttttg ccaagacaac cacagaagtg
     4441 atactgtgct attcttagtg cctcctagcg gagggtggtg gtaacttttt gttttggttt
     4501 tttttttttt tttgagacgg agtcccgctc tgtcacccag gatggagtgc agtggcgcaa
     4561 tctcggctca ctgcaacctc tgcctcctgg gttcaaagtg attctcctgc ctcagcctcc
     4621 tgagtagctg ggattgcagg tgcccaccac cacacccagc taatttttgt atttttagta
     4681 gagacaggtt ttcgccatgt tggccaggct ggtcttgaac tcctgacctc aggtgatcca
     4741 cccacctcgg cctcccaaag tgctgagatt acaggcatga gccaccacac ctagactagg
     4801 tggtggtaac tttgatcaca tggctaaggt ggtgtgtgcc aggtttctcc actgtaaaat
     4861 taggaatttt ccctttgaaa ttaacaagaa tcttccactt tgaagctatg tgaatgtctt
     4921 attcttaaaa ttttgcctac tgattttcat ttccatcatc aatgattctt gcttataaca
     4981 ggtattaatg ttatgcttgc ctaatggtga ctttgtttca ttattttacc tgtatttatt
     5041 aattggtatt ctactataag gaagagctgt cccttttccc catttattta tttgataatt
     5101 tatatcagta tgaatgagtg gatatctgtt ttattctaca ggctacaatc taatgctaac
     5161 agtttatttg gttgctcaaa ttggctcaga tttggccagt gagaactcat tgaagttggc
     5221 actgtgttgt ttcgacattg cccctgtcac tttttaagca ttttctggca ccacaagatg
     5281 tttcaggctt cctcacattt tccctatctc agccctggca tcagtcattc tctaagaagc
     5341 tcccagttcc ttttattcca gaaaaaagga acttagaaac caagttgttt cttgatgcca
     5401 ctggaaacca agatctggac agaatatata ctcctggcta gagtatcatt ggcggagtgt
     5461 cattgcttgt aggcctgctc agcagacaga gctagaaaac atatatgtat atatgttaaa
     5521 acatgcaaat acaagcacct gaatttatta ttctatccat ctgtatgtta ttaaaaaccg
     5581 tgagccaggt atggtggctc gtgcctgtat cccaggactt tgggaggcca aagtgggagg
     5641 atcacttgag cccaggagtt caagaccagc ctgcgcatca tagcaagacc tcatcctcca
     5701 aacgtttaaa aaataaaaaa ttagccaggc atggtggtgc attcctgtaa tcctagctac
     5761 gtaggaggct gaggcaggag gatcgcttga gttcagaagg ttgaggctgt agtgaactgt
     5821 gattgtacca ctgcactgca gcctgagtga cagagcaaga ctccgtttca tatttttaaa
     5881 aataaataaa aatcatgagt ttagatacgg ttttaattca ataccatagg gtttgcgact
     5941 gccattttta taaccttact attctttttc tgctttttct cctgctatct ctgtttctgc
     6001 tcctttctat ttgatgttta gacttcccat agaggctcta gttaagtcag ctagtaacca
     6061 gcctgtgtgc agtattccta ctagatagag gtcttatgcc cggctgtcag tccgttggtt
     6121 cagttaactg tggccaggaa tactaggcat ataacttaaa atcagataac ttttatacaa
     6181 gaaaagccaa tggccacctt cctgagaata ggataaggag acaggggtag aaccttagat
     6241 tctaaggaac ctaattaaga atcacttctg gccgggcgtg gtggctcatg cctgtaatcc
     6301 caacactctg gaggccatgt aggggcagat cacgagatca agagattgag accatcctga
     6361 ccaacatggt gaaaccccat ctctactaaa aatacaaaaa ttagccaggc gtggtggcgg
     6421 gcgcctgtag tctcagctac tcgggaggct gaggcaggag aatcgcttga acccgggagg
     6481 tggaggttgc agtgagccga aattgtgcca ctgcactcca gcctggtgac agagccagcc
     6541 tccgtctcca acaaaaacaa acaaaaaaag aattacttct tccagagatt ctctgccaga
     6601 actcctaggt ggtgttggac ccatatcttt tacttccata gcatcccagg ctcagctcac
     6661 ttgtcctact tgttctgtgt cttcatcact agaatgtaag ttctaagagg gcagatgcca
     6721 agctgttcag ccattcacag aacctggcac agtgcaggca tatgacagat gttcctttat
     6781 tattatactt gggtgagtgg atgggacctg cagcaagtgc agatcttctc agtgggctct
     6841 ggaacagaaa agtattgttt gtttgctcag catattttta tttgtcccat gttgctgtgg
     6901 ccaggatttg agctctgaga caatgcagca aggtgagacc cagatttctt ttgttttgtt
     6961 ttgttttttg agacagagtc ttgctctgtc gcccaggctg gagtgcggtg gtgcaatctt
     7021 ggctcactgc aacctccacc tccagttcaa gcaggtctca tgcctcagcc tcctcagtag
     7081 ctgggactac aggcatatgc caccataccc agctaatttt ttttgtattt ttagtaaaga
     7141 cggggtttca ccatgtttgc caggctagtc tcaaactcct ggtctcaagt gatccaccca
     7201 ccttggcctc ccagagtgct gagattacaa gcgtcaacga ctgtacccgg ccccaaattc
     7261 cttattgagg atcctagaat acatgagacc agacttggaa atgaaagtgt aacatgttta
     7321 ttgttcaaaa agaaaaactc aaaggtgtgt agtgatttta aaatttaggg aaattcctca
     7381 atatagtgaa agaagaaaaa caagaaagaa atttaggaaa gaaacacact taaaccataa
     7441 aaaatagaaa atggaccaat aaagataaaa gctaaactta acaaggtagg aaaaagaaaa
     7501 agaataaatt aaaaaattct ttgaaagcac caataaaata gataaaacct cctgagcctg
     7561 ataaaagggg aaaggagcca aaaaaattaa caaaattagg catgagaaat tagacataac
     7621 catatatatt gaggaattga gaagaagaat agaactctat ggcaacaaat ttgaaatcag
     7681 aggaaatgga taatttccca gcaaacactg atcctagaaa tagtttgaat aggccagttg
     7741 gttacccaag aagaaactgg aaaggtggtt aaaattttat cctttttgag caccataaga
     7801 tggtgaaaaa taaataaaat tttatccttg taaaagattg atggccaggc atggtggtgg
     7861 cccacacctg taatcctagc actttggaag gccaaggcag gcagatcact tgagccccgg
     7921 agtctgagac cagcctgggc aacatggcaa gaccccacct ctactaaaaa taccaaaatt
     7981 agccaggcat gatggtgctt gcctgtagtc aacagctact tgggaggctg aggtggggaa
     8041 gatggtttaa gcccaggagg cagaggttgc agtgagccaa gactgtgctg ctgcactcca
     8101 gcctgggtga cagagcgaga ccatgtccca aaaataaaaa attgttttta attaaacttt
     8161 ttaattgaaa aatatatggg aaattgtaca aatcacaagt atgcagctca gtgaatgatt
     8221 acaaagtaaa cacactccta tagccatcac tcaaccccca aaatagatga gttttaacta
     8281 ttattgtact caaacctgat aaagtgccag aaagaatgct atagcctaat ctcacctatg
     8341 gccatagatg caaaaatccc aaataaaatc aagttgaatt gcacactctg attacataag
     8401 gtttatttta gcaatgcaag gctcagtgtc aggaaattta ttaatttatt acatcaagaa
     8461 cttaaatgtt atttaaatgt ctagagagtg ctagtgttgt taaattttct cattttgata
     8521 attatactat gattacagaa gagaacgtcc ttgttttcag aaaatgtaag tatttagagg
     8581 ttaaaggtaa acctctaatt tggtttgcca gtatttcaga taactacaca cacacacaca
     8641 cacacacaca cacacacgga atgataaagc aaaaagtaag gtgttggcaa ggcatggtgg
     8701 ctcacacctg taattccaac actttgggag gcccaggcag gtggatcacc taggtctgga
     8761 gttcgagacc agcctggaca acatggtgaa acccctcttt attaaagtac aaaaattagc
     8821 cggacatagt ggcacatgcc ggtaattcca gctatttggg aggctgaggc acaggaatcc
     8881 cttgaacctg gaggcagagg ttgtagtgag cctacatcac accactgcac tccagcctgg
     8941 atgacagagt gagactgtct caaaaacaaa caaaaaaaag atgttaacat ttgggaaatc
     9001 tgagggaatg atgtacatga attctttgta ttgtttttgc aacttttaag tataaagtta
     9061 tttcaggcca ggcatggtag tgcatgcctg tatacccagc tactcgaggc tgaggtggaa
     9121 gattccttga gtctaggagt atgaggttac agtgagctat gatcatgcca ctgcactcca
     9181 ggctgggtgg cagagtgaca ccctatctct taaaaaaaaa aaaaaaaaaa aaaacaggtg
     9241 cagtatctca cacctgtaat ctcaacagaa cactgagggg tcaaggcagg tggactgctt
     9301 gagcccagga gttcaagacc agcctgagca acatggtgaa accccatctc tgcaaaaaat
     9361 tagctggttg tggtggcatc cacctgtggt ctcagctact tgggaggctg aggtgggaat
     9421 ataactggag ctcaggaggt ggaggttgct gtgagatgag atcgtgccac tgcactccag
     9481 cctatctcca aaaaaaaaaa aaaggctata gtagaagcct attagcatgg ataagtgtct
     9541 gaataaaaga taactgtaca aaaatcaatt gttttttctg tattctagca ataatcaact
     9601 agaaacagta tcaaaagaaa aacattccat ttacaattgc aacaaatagg tatatatata
     9661 tttgctcttc tacacataac ctatttctgg aagggagcag aactgggcaa ttcagggaca
     9721 gcaatggaag gggaacactg ctatgttatt ttaaatactt tttagtaagc tttgaaccat
     9781 attaatgtat tacctgttca aaattatact taataaattt aacaagaaaa ccatattgaa
     9841 gggcataaaa ataagacctg acaagtgaaa aaacatcaag ttttagaaag gatgatttaa
     9901 tactaaaata tacatttctt aatatataac ttaatgtaaa cctaataaat aatttaatac
     9961 aaa
//
