LOCUS       NM_001352514            8273 bp    mRNA    linear   PRI 20-SEP-2024
DEFINITION  Homo sapiens holocarboxylase synthetase (HLCS), transcript variant
            4, mRNA.
ACCESSION   NM_001352514
VERSION     NM_001352514.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 8273)
  AUTHORS   Cronan,J.E.
  TITLE     Biotin protein ligase as you like it: Either extraordinarily
            specific or promiscuous protein biotinylation
  JOURNAL   Proteins 92 (4), 435-448 (2024)
   PUBMED   37997490
  REMARK    GeneRIF: Biotin protein ligase as you like it: Either
            extraordinarily specific or promiscuous protein biotinylation.
            Review article
REFERENCE   2  (bases 1 to 8273)
  AUTHORS   Sun,L., Li,F., Bai,S. and Bi,C.
  TITLE     CircRNA HLCS regulates lens epithelial cell apoptosis via
            miR-338-3p/BPNT1 axis
  JOURNAL   Int Ophthalmol 44 (1), 142 (2024)
   PUBMED   38493427
  REMARK    GeneRIF: CircRNA HLCS regulates lens epithelial cell apoptosis via
            miR-338-3p/BPNT1 axis.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 8273)
  AUTHORS   Ling,S., Qiu,W., Zhang,H., Liang,L., Lu,D., Chen,T., Zhan,X.,
            Wang,Y., Gu,X. and Han,L.
  TITLE     Clinical, biochemical, and genetic analysis of 28 Chinese patients
            with holocarboxylase synthetase deficiency
  JOURNAL   Orphanet J Rare Dis 18 (1), 48 (2023)
   PUBMED   36890565
  REMARK    GeneRIF: Clinical, biochemical, and genetic analysis of 28 Chinese
            patients with holocarboxylase synthetase deficiency.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 8273)
  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   5  (bases 1 to 8273)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   6  (bases 1 to 8273)
  AUTHORS   Aoki,Y., Suzuki,Y., Sakamoto,O., Li,X., Takahashi,K., Ohtake,A.,
            Sakuta,R., Ohura,T., Miyabayashi,S. and Narisawa,K.
  TITLE     Molecular analysis of holocarboxylase synthetase deficiency: a
            missense mutation and a single base deletion are predominant in
            Japanese patients
  JOURNAL   Biochim Biophys Acta 1272 (3), 168-174 (1995)
   PUBMED   8541348
REFERENCE   7  (bases 1 to 8273)
  AUTHORS   Leon-Del-Rio,A., Leclerc,D., Akerman,B., Wakamatsu,N. and
            Gravel,R.A.
  TITLE     Isolation of a cDNA encoding human holocarboxylase synthetase by
            functional complementation of a biotin auxotroph of Escherichia
            coli
  JOURNAL   Proc Natl Acad Sci U S A 92 (10), 4626-4630 (1995)
   PUBMED   7753853
REFERENCE   8  (bases 1 to 8273)
  AUTHORS   Suzuki,Y., Aoki,Y., Ishida,Y., Chiba,Y., Iwamatsu,A., Kishino,T.,
            Niikawa,N., Matsubara,Y. and Narisawa,K.
  TITLE     Isolation and characterization of mutations in the human
            holocarboxylase synthetase cDNA
  JOURNAL   Nat Genet 8 (2), 122-128 (1994)
   PUBMED   7842009
REFERENCE   9  (bases 1 to 8273)
  AUTHORS   Chiba,Y., Suzuki,Y., Aoki,Y., Ishida,Y. and Narisawa,K.
  TITLE     Purification and properties of bovine liver holocarboxylase
            synthetase
  JOURNAL   Arch Biochem Biophys 313 (1), 8-14 (1994)
   PUBMED   8053691
REFERENCE   10 (bases 1 to 8273)
  AUTHORS   Narisawa,K., Arai,N., Igarashi,Y., Satoh,T., Tada,K. and Hirooka,Y.
  TITLE     Clinical and biochemical findings on a child with multiple
            biotin-responsive carboxylase deficiencies
  JOURNAL   J Inherit Metab Dis 5 (2), 67-68 (1982)
   PUBMED   6133032
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP000704.2, AP000703.1,
            AP000702.1, AP000698.1 and AP000697.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_001352514.1.
            
            Summary: This gene encodes an enzyme that catalyzes the binding of
            biotin to carboxylases and histones. The protein plays an important
            role in gluconeogenesis, fatty acid synthesis and branched chain
            amino acid catabolism. Defects in this gene are the cause of
            holocarboxylase synthetase deficiency. Multiple alternatively
            spliced variants, encoding the same protein, have been
            identified.[provided by RefSeq, Jun 2011].
            
            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 :: SRR18074969.659626.1,
                                           SRR18074967.1700400.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000674895.3/ ENSP00000502087.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-226               AP000704.2         22367-22592         c
            227-361             AP000704.2         17959-18093         c
            362-524             AP000703.1         31690-31852         c
            525-1468            AP000703.1         29307-30250         c
            1469-1651           AP000703.1         23109-23291         c
            1652-1923           AP000702.1         7840-8111           c
            1924-1991           AP000698.1         10612-10679         c
            1992-2152           AP000698.1         8406-8566           c
            2153-2267           AP000698.1         3121-3235           c
            2268-2416           AP000698.1         1-149               c
            2417-2481           AP000697.1         129965-130029       c
            2482-8273           AP000697.1         122049-127840       c
FEATURES             Location/Qualifiers
     source          1..8273
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="21"
                     /map="21q22.13"
     gene            1..8273
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /note="holocarboxylase synthetase"
                     /db_xref="GeneID:3141"
                     /db_xref="HGNC:HGNC:4976"
                     /db_xref="MIM:609018"
     exon            1..226
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     CDS             32..2653
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /EC_number="6.3.4.10"
                     /EC_number="6.3.4.11"
                     /EC_number="6.3.4.15"
                     /EC_number="6.3.4.9"
                     /note="isoform 2 is encoded by transcript variant 4;
                     holocarboxylase synthetase (biotin-(proprionyl-Coenzyme
                     A-carboxylase (ATP-hydrolysing)) ligase); biotin
                     apo-protein ligase;
                     biotin--[methylmalonyl-CoA-carboxytransferase] ligase;
                     biotin--[methylcrotonoyl-CoA-carboxylase] ligase;
                     holocarboxylase synthetase
                     (biotin-(proprionyl-CoA-carboxylase (ATP-hydrolysing))
                     ligase); biotin--[acetyl-CoA-carboxylase] ligase"
                     /codon_start=1
                     /product="biotin--protein ligase isoform 2"
                     /protein_id="NP_001339443.1"
                     /db_xref="CCDS:CCDS93094.1"
                     /db_xref="GeneID:3141"
                     /db_xref="HGNC:HGNC:4976"
                     /db_xref="MIM:609018"
                     /translation="MLITLCYLYLWARWGRRPAELVRATVRRLRASRCSFTFCGAAAQ
                     PPGARVCLSRGGRVFCVSDSQSIEDLNKWALFLVSPFILEAEHIAFVTESIWVQSENL
                     QRSSSSETIVKWSDCCLPLACRPGDPYRLIAEASVDNFSKLGVAFMEDRLHMDNGLVP
                     QKIVSVHLQDSTLKEVKDQVSNKQAQILEPKPEPSLEIKPEQDGMEHVGRDDPKALGE
                     EPKQRRGSASGSEPAGDSDRGGGPVEHYHLHLSSCHECLELENSTIESVKFASAENIP
                     DLPYDYSSSLESVADETSPEREGRRVNLTGKAPNILLYVGSDSQEALGRFHEVRSVLA
                     DCVDIDSYILYHLLEDSALRDPWTDNCLLLVIATRESIPEDLYQKFMAYLSQGGKVLG
                     LSSSFTFGGFQVTSKGALHKTVQNLVFSKADQSEVKLSVLSSGCRYQEGPVRLSPGRL
                     QGHLENEDKDRMIVHVPFGTRGGEAVLCQVHLELPPSSNIVQTPEDFNLLKSSNFRRY
                     EVLREILTTLGLSCDMKQVPALTPLYLLSAAEEIRDPLMQWLGKHVDSEGEIKSGQLS
                     LRFVSSYVSEVEITPSCIPVVTNMEAFSSEHFNLEIYRQNLQTKQLGKVILFAEVTPT
                     TMRLLDGLMFQTPQEMGLIVIAARQTEGKGRGGNVWLSPVGCALSTLLISIPLRSQLG
                     QRIPFVQHLMSVAVVEAVRSIPEYQDINLRVKWPNDIYYSDLMKIGGVLVNSTLMGET
                     FYILIGCGFNVTNSNPTICINDLITEYNKQHKAELKPLRADYLIARVVTVLEKLIKEF
                     QDKGPNSVLPLYYRYWVHSGQQVHLGSAEGPKVSIVGLDDSGFLQVHQEGGEVVTVHP
                     DGNSFDMLRNLILPKRR"
     exon            227..361
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     exon            362..524
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     exon            525..1468
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     exon            1469..1651
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     exon            1652..1923
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     exon            1924..1991
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     exon            1992..2152
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     exon            2153..2267
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     exon            2268..2481
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     exon            2482..8273
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4829..4834
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /note="hexamer: AATAAA"
     polyA_site      4849
                     /gene="HLCS"
                     /gene_synonym="HCS"
     regulatory      5685..5690
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /note="hexamer: AATAAA"
     polyA_site      5707
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /note="major polyA site"
     regulatory      8252..8257
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HLCS"
                     /gene_synonym="HCS"
                     /note="hexamer: AATAAA"
     polyA_site      8273
                     /gene="HLCS"
                     /gene_synonym="HCS"
ORIGIN      
        1 aaggcgggct cgccctgccg gcggcgcggc catgctcatc acgctgtgct acctgtacct
       61 gtgggcgcgc tggggtcgcc ggccggctga gctcgtgcgc gccacggtgc ggcggctgcg
      121 tgcctcgcgc tgttccttca ccttctgcgg cgcggccgcg cagcccccgg gcgcccgcgt
      181 gtgcctgagc cgtggcggcc gcgtcttctg cgtcagcgac agccagtcca ttgaagactt
      241 gaacaagtgg gccctatttc ttgtgtctcc ttttatactt gaagcagaac acatagcatt
      301 tgtgacggag agcatttggg tacaaagtga gaatttacag agatcatcct cttcagaaac
      361 aattgtcaag tggtcagact gttgtttgcc attagcttgc agacctgggg atccttatcg
      421 gctaattgct gaagcaagtg tggacaactt cagcaagctg ggggtggcgt tcatggaaga
      481 tagactccac atggataatg gactggtacc ccaaaagatt gtgtcggtgc acttgcagga
      541 ctccactctg aaggaagtta aggatcaggt ctcaaacaag caagcccaga tcctagagcc
      601 gaagcctgaa ccttctcttg agattaagcc tgagcaggac ggtatggagc atgttggcag
      661 agatgaccca aaggctcttg gtgaagaacc caaacaaagg agaggcagtg cctctgggag
      721 tgagcctgct ggggacagtg acaggggagg gggccccgtt gagcattatc acctccatct
      781 gtctagttgc cacgagtgtc tggaacttga gaacagcacc attgagtcag tcaagtttgc
      841 gtctgccgag aacattccag accttcccta cgattatagc agcagtttgg agagtgttgc
      901 tgatgagacc tcccccgaaa gagaagggag gagagtcaac ctcacgggaa aggcacccaa
      961 catcctcctc tatgtgggct ccgactccca ggaagccctc ggccggttcc acgaggtccg
     1021 gtctgtgctg gccgactgtg tggacattga cagttatatt ctctaccacc tgctggagga
     1081 cagtgctctc agagacccgt ggacggacaa ctgtctgctg ttggtcattg ctaccaggga
     1141 gtccattccc gaagacctgt accagaagtt catggcctat ctttctcagg gagggaaggt
     1201 gttgggcctg tcttcatcct tcacctttgg tggctttcag gtgacaagca agggtgcact
     1261 gcacaagaca gtccagaact tggttttctc caaggctgac cagagcgagg tgaagctcag
     1321 cgtcttgagc agtggctgca ggtaccagga aggccccgtc cggctcagcc ccggcaggct
     1381 ccagggccac ctggagaatg aggacaagga caggatgatt gtgcatgtgc cttttggaac
     1441 tcgcggggga gaagctgttc tttgccaggt gcacttagaa ctacctccca gctccaacat
     1501 agtgcaaact ccagaagatt ttaacttgct caagtcaagc aattttagaa gatacgaagt
     1561 ccttagagag attctgacaa cccttggcct cagctgtgac atgaaacaag ttcctgcctt
     1621 aactcctctt tacttgctgt cagctgcgga ggaaatcagg gatcctctta tgcagtggct
     1681 tgggaaacat gtggactccg agggagaaat aaaatccggc cagctctctc ttagatttgt
     1741 ttcatcctac gtgtctgaag tagaaataac cccatcttgt atacctgtgg tgaccaacat
     1801 ggaggccttc tcatcagaac atttcaactt agagatctat cgccaaaatc tgcagaccaa
     1861 gcagttgggg aaagtaattt tgtttgccga agtgaccccc acaacgatgc gtctcctgga
     1921 tgggctgatg tttcagacac cgcaggaaat gggcttaata gtgatcgcgg cccggcagac
     1981 cgagggcaaa ggacggggag ggaatgtgtg gctgagccct gtgggatgtg ctctttctac
     2041 tctgctcatc tccattccac tgagatccca gctgggacag aggatcccgt ttgtccagca
     2101 tctgatgtcc gtggctgtcg tggaagcagt gaggtccatt cccgagtatc aggatatcaa
     2161 cttacgagtg aagtggccca acgatattta ttacagtgac ctcatgaaga tcggcggagt
     2221 tctggttaac tcaacactca tgggagaaac attttatata cttattggct gtggatttaa
     2281 tgtgactaac agtaacccta ccatctgcat caacgacctc atcacagaat acaataaaca
     2341 acacaaggca gaactgaagc ccttaagagc cgattatctc atcgccagag tcgtgactgt
     2401 gctggagaaa ctgatcaaag agtttcagga caaagggccc aacagcgtcc ttccccttta
     2461 ttaccgatac tgggtccaca gtggtcagca agtccatctg ggcagcgcag agggaccaaa
     2521 ggtgtccatc gttggcctgg acgattctgg cttcctccag gttcaccagg agggcggcga
     2581 ggttgtgact gtgcacccgg acggcaactc cttcgacatg ctgagaaacc tcatcctccc
     2641 caaacggcgg taatgccggg cgtccccgag acgcggctgc ctgtccgtgc ccatgcatct
     2701 ggaaatctaa tttagagttg taggtgaatt ttcttttcct ccaattcatt tgttaagtct
     2761 ttgttctttt tctgtgtttc tgtttgtttt taggtttgtt ttgttgtcgt tttctttggt
     2821 gtttgaagag gctctgggat agatggttaa gaagtagaaa atttagttta gggaaagccc
     2881 tcccacaggt gggaaattgc tctcccctct gtggcttgga cttacgttta ttgtcaaggg
     2941 gagtttttac atggaaatga caatgggaaa attcagatat tttcttagta gtgcagacct
     3001 ttacccctag tctatgaaaa aacaaaccaa aatatgctct tgcgcccagg ccagtggtga
     3061 gttagaggta tgctatcact gtttgtaagc atctggggag gtactgaact gtaagaacat
     3121 gcttggacac ttagtcattg ttctgtgttt ttattaatga agaaaaggga agacagactt
     3181 ccaagagtta ctgtccaccc ggtggtgtgg ccccatagcg aagtctaaat gcctgtagag
     3241 atagagctag ctggtgtggt tgcagtgacc ttgtagagga aatcagttca ttactttgac
     3301 atcattcagt gagctctcct ttcctaagga agtttaaatg tccttagtta gggactgact
     3361 ttcttaagta agtttaaatt tactacatat tgtgaagaga caggatcaag ttcagaatcc
     3421 ttaaatgtct gattaggcat cacttggatg aggaggtggg cgatttggct ctgacagctg
     3481 gagatgaagg cacactcata ccacatacaa gggaggattt ggagctttta agccagtttc
     3541 agatttactc tgaaatgtgg agcattcctg caagactgtg cagctcacgg aatatagaag
     3601 acatggcatt ttactcagaa gtcataagtt tttgcccccc tcatttacct cgtattacca
     3661 agaaagaaaa tgttatcgat actaaacacc atcagttcag agggaggatg tgtgtgtgtg
     3721 cccgcatatg tgtgtgcgtg cgtgtgtgcg cacatagctt taaaagaaga cattcaaaat
     3781 ttgatgtgct acaagcctca tgaaagaaca aaagaaatga agccttttga tatgcattcg
     3841 ctattcccag atgtacgcca tgccttttcc atgtccctcc tatctctgtt gaacttatga
     3901 atcatactca ttacttttca gctttttaaa aggccaattt ttgtccagtt ttctctcttc
     3961 cagtcccagc tgaaattagt ggaaagaaag tttgatggag ctttcagctt tgaacaaaat
     4021 cccttcattg taaactagca ccatctttat ccaggtctta cccagtcagg ctaattccag
     4081 aaacttgtgg tttttagtat agtctgtcta cctttagcca ggcacaggac agccctatga
     4141 aaaaataccc aatatatatt ttttggaaat gaaacattaa aagaacttaa aaagtaattt
     4201 ttggaaatga ggcttcaatt agaattattt ttctcaaaaa acaaacaaac aaaaaacaca
     4261 aaaaaaacca ctcttctcca aatgcccaag ccttctttca aaattagtta gaaacttaag
     4321 taaaatacaa gtccacacca tccccaaatt acaaaatgga cttacccttg agagggcatc
     4381 tgcagaatat catcagggac aaagatctcg aggctaacga tgtaggtttc atttctcaga
     4441 ctttgtaata taaggcaagc cctctctcag agctgccatc atcacttttt gaatttcttt
     4501 gggggttatt taatgaaaaa catgctatgt tttgttttaa gctgaagtcc tattctggac
     4561 actctgcttt gggaaaaaat gttatcattt aatttccttt ctgcaaatta aaactaatga
     4621 agtgtggcct tgtcaaaggc tatggagatg ttccgggcat actgctgtgc tctgtgcttt
     4681 ccagcaggcg ctcctccctc acgcaggaga ctcagttgtc ctgagagaga tgaagcagcc
     4741 ttgaagcaga tgctgcgttt tccataaacc tgattttgcc tcacatgaac caaagactct
     4801 caaaactccg cttctataga attagctgaa taaaggcatt ttactgatag ctgttcgtgt
     4861 tagcgaaacc tgtctacctg ctatagcaca ctctccgatt tgggccattt atgcaccccg
     4921 caacctggga tctcaaggag ctttaaagtc ttaatgggaa cttggcattt tcctgatgat
     4981 ctttaaaatg tggtcactaa actcaggatt ggcgtgtgct tttagaacac tggagtagcc
     5041 cttgttttag aggctgtgca ttgagtatcg accgtatttt gtaaaaggca agatatcctc
     5101 ccttccaggc tggtaacggg tttcaagggg actcttgagg aagtgccccc taaaatagaa
     5161 cacagcaata actgggcttc ctgtccccac ccccacccca gcagtgctct ctggcactgg
     5221 gaactctgct agggagtggt ggaagtagga aggatttgtg tgcaaaggaa aatcgtggtt
     5281 gagtttcact gcagcaggct gacgttgcct gatgtgagag caagtggccg actggggtgc
     5341 gggtgcacag gtcgggggag cacaggccac agagcgcagc ctctgggggt cccccaaggc
     5401 acagcatata cagcatggtc gccccttgcc ctggagtctg ggaacaaaga gaggagccag
     5461 cctccccgca ctgcttcaga tggaaaaggg aggcagggtg ggcttccgtt ctccagatct
     5521 gtttgctctt aacaggcaga acatgggaga atccttattc ctggttaatc actatgcata
     5581 tttgaaataa aagaaagcgt aagcctctgc aattttaact tctcaaagga tgtctctgaa
     5641 aagaatcact ttaaaccaat gcctataaaa agcaagtcta ccaaaataaa ctaagacttt
     5701 ctatgtggtt tgggctccct cttattttta caagtttcat ttttaaaagt aggcaactac
     5761 tttgggttac agtattttta ttcatattta aacattttta caaaataaat aaagtgtttt
     5821 acatagtaag gaatatgtac gtatttccaa gtattaagaa gccaagtgtt tttttttttg
     5881 acgtattatt gacaaatgta ttcagcgcca tacacaagag aaatattatt actccaaaga
     5941 acgaaagtta acaaaactcc aaagcaaaaa cccttttaat ggaggtgaga aataaattta
     6001 atgtaacaac agctagattg tttttaggat ttttcttttc ttttgtggaa acttcttgac
     6061 ttgacttttc atctgaacag tttttccccc caagatttta atcttatatg tcatacttaa
     6121 gtttaggaac agcttgaata attagcattc tagataacac aagggccatg attcactaaa
     6181 attccaagct actgtaattt tatggcattt atttgcaaat gttctttgta tctcatttta
     6241 tctgtagcag tccccactag tctaccttaa ccatcttata gctctggtaa attaaaactt
     6301 acgtagactt tatacaagat ccattggccg tattaaacct cccccactct tagggcttag
     6361 ggcggaaggg acgaaggcag ggctgatagg acttttaaaa ggataaaagg agtgggggca
     6421 agggaggcgg aaaatacagg ctcttgcaga taccctccgc gctgccctcc acacccagcc
     6481 cactgctcta caaaggtatg aatggaatgg cttttctaga aaagggcttc caagaacata
     6541 aaggaattcc tttccctggg aggccccgtg gagggctgag ccagccttga attgggctta
     6601 tttctcaaat ccatttgatc tggcattttt gtcaacatgg tacatgttag ggcctacgat
     6661 gatttttttt tcttttttgt aaaagagagg catatgtatt aaaatgcttc ctcttcccct
     6721 gccggagcct cacagaagtc aagaaacgct atccccagct taaatgtgca gactcttcaa
     6781 gatggaggtc acaatattag gttgccacag taacagctct gctgacttca cactcagccc
     6841 tggccgtcct gaagccagct cgtgtaagaa tcttccttca tgttctaggt tatgaaaacg
     6901 aagtttgttt agacaaggac gttttcacta gtacacattt tcaagtacat acacactctg
     6961 ttacgcctgt ccacgttgtc acttgtaaat ctatgatagg gtcttttttc tcaacagtaa
     7021 cctttgttat tgaactgctc cgatagcctt gatttatttt tactaaatac agccccaaaa
     7081 gttaataaca aggtagacac aaaagcattt tgcagtactt tattgaaaaa tgtcggtggt
     7141 atctcctagt aatcaaacct acacctttca agaatcacgg tttaattaca agactcatga
     7201 acataaaaaa ataataccct cggcttattt cctgtgcaca cactcacaag gagctgtgaa
     7261 tgaggtatag ctgagtgcgt ggagaggcgg gcacatccct tcctaccatc cagccccttc
     7321 gctgcatgac ccacggtcct aaatttgcaa attgtgactc ttaccatgag gcccactgac
     7381 agacaccctg tagggattgt gtcaggtcct cactaagtga cacagggttg gcaaaaaaaa
     7441 aaaaaaaaaa gtcagttcac attttgagag cagttggtgt aggtgcactt gattttagaa
     7501 cgatgagttt aaaacatttg tgaaaacctc tttccattca gaaaggtgga aaaagtttcc
     7561 taaaataaac cattttgata aagcagcaaa atgctgcagt gttgatagtg tgaagaaaat
     7621 tgaaggacgg cggttcaatg cattgtgcag ttcagagcca tgacaggatt tttccatgtt
     7681 gagatcttta agcaaaaccc ataaaaagta aaaattaatg gaagctcatt ttttaaacac
     7741 tgctggtgct ttatgaaagg atttctgttt acctgttgca cacgtaacat gttcttacga
     7801 agttttctcg ctgtgtagaa aatgcttaaa atgtctacat cattttcatt acaccccctt
     7861 aagcatgttt ttccttcaca aggtgcagtc cattgacagt gttccgtatt gcacgtgcaa
     7921 tttaacttta ttagcactat ttgtagcaaa cacgagccta gtgaattaca gatctgtgtg
     7981 ggccagaggg attttgccac gtaataatga agcttgacag ggtcattctc ataaactgtc
     8041 tggctacata tatatttttg catttaatgc ctattcaata tattctgaag gtgctactct
     8101 tggtgttatc aagagttcat aggggttagg gggaagtaag agcttgttaa tgtatttggg
     8161 aagcacacct atgttcacag acacaaaatg gaattgcatg gtcaccccct tagtcttggt
     8221 ttgttggctt tttgtattga agaaagggtt aaataaaaac aaaaataatg aga
//
