LOCUS       NM_003879              14612 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens CASP8 and FADD like apoptosis regulator (CFLAR),
            transcript variant 1, mRNA.
ACCESSION   NM_003879
VERSION     NM_003879.7
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 14612)
  AUTHORS   Yang,C.Y., Lien,C.I., Tseng,Y.C., Tu,Y.F., Kulczyk,A.W., Lu,Y.C.,
            Wang,Y.T., Su,T.W., Hsu,L.C., Lo,Y.C. and Lin,S.C.
  TITLE     Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP
            complexes regulating apoptosis
  JOURNAL   Nat Commun 15 (1), 3791 (2024)
   PUBMED   38710704
  REMARK    GeneRIF: Deciphering DED assembly mechanisms in
            FADD-procaspase-8-cFLIP complexes regulating apoptosis.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 14612)
  AUTHORS   Gao,Y., Yu,S., Chen,M., Wang,X., Pan,L., Wei,B. and Meng,G.
  TITLE     cFLIPS regulates alternative NLRP3 inflammasome activation in human
            monocytes
  JOURNAL   Cell Mol Immunol 20 (10), 1203-1215 (2023)
   PUBMED   37591930
  REMARK    GeneRIF: cFLIPS regulates alternative NLRP3 inflammasome activation
            in human monocytes.
REFERENCE   3  (bases 1 to 14612)
  AUTHORS   Yang,W.J., Han,F.H., Gu,Y.P., Qu,H., Liu,J., Shen,J.H. and Leng,Y.
  TITLE     TGR5 agonist inhibits intestinal epithelial cell apoptosis via
            cAMP/PKA/c-FLIP/JNK signaling pathway and ameliorates dextran
            sulfate sodium-induced ulcerative colitis
  JOURNAL   Acta Pharmacol Sin 44 (8), 1649-1664 (2023)
   PUBMED   36997665
  REMARK    GeneRIF: TGR5 agonist inhibits intestinal epithelial cell apoptosis
            via cAMP/PKA/c-FLIP/JNK signaling pathway and ameliorates dextran
            sulfate sodium-induced ulcerative colitis.
REFERENCE   4  (bases 1 to 14612)
  AUTHORS   Rasper,D.M., Vaillancourt,J.P., Hadano,S., Houtzager,V.M.,
            Seiden,I., Keen,S.L., Tawa,P., Xanthoudakis,S., Nasir,J.,
            Martindale,D., Koop,B.F., Peterson,E.P., Thornberry,N.A., Huang,J.,
            MacPherson,D.P., Black,S.C., Hornung,F., Lenardo,M.J., Hayden,M.R.,
            Roy,S. and Nicholson,D.W.
  TITLE     Cell death attenuation by 'Usurpin', a mammalian DED-caspase
            homologue that precludes caspase-8 recruitment and activation by
            the CD-95 (Fas, APO-1) receptor complex
  JOURNAL   Cell Death Differ 5 (4), 271-288 (1998)
   PUBMED   10200473
REFERENCE   5  (bases 1 to 14612)
  AUTHORS   Goltsev,Y.V., Kovalenko,A.V., Arnold,E., Varfolomeev,E.E.,
            Brodianskii,V.M. and Wallach,D.
  TITLE     CASH, a novel caspase homologue with death effector domains
  JOURNAL   J Biol Chem 272 (32), 19641-19644 (1997)
   PUBMED   9289491
REFERENCE   6  (bases 1 to 14612)
  AUTHORS   Srinivasula,S.M., Ahmad,M., Ottilie,S., Bullrich,F., Banks,S.,
            Wang,Y., Fernandes-Alnemri,T., Croce,C.M., Litwack,G.,
            Tomaselli,K.J., Armstrong,R.C. and Alnemri,E.S.
  TITLE     FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates
            Fas/TNFR1-induced apoptosis
  JOURNAL   J Biol Chem 272 (30), 18542-18545 (1997)
   PUBMED   9228018
REFERENCE   7  (bases 1 to 14612)
  AUTHORS   Kim,T.W., Pettingell,W.H., Jung,Y.K., Kovacs,D.M. and Tanzi,R.E.
  TITLE     Alternative cleavage of Alzheimer-associated presenilins during
            apoptosis by a caspase-3 family protease
  JOURNAL   Science 277 (5324), 373-376 (1997)
   PUBMED   9219695
REFERENCE   8  (bases 1 to 14612)
  AUTHORS   Hu,S., Vincenz,C., Ni,J., Gentz,R. and Dixit,V.M.
  TITLE     I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1- and
            CD-95-induced apoptosis
  JOURNAL   J Biol Chem 272 (28), 17255-17257 (1997)
   PUBMED   9211860
REFERENCE   9  (bases 1 to 14612)
  AUTHORS   Irmler,M., Thome,M., Hahne,M., Schneider,P., Hofmann,K.,
            Steiner,V., Bodmer,J.L., Schroter,M., Burns,K., Mattmann,C.,
            Rimoldi,D., French,L.E. and Tschopp,J.
  TITLE     Inhibition of death receptor signals by cellular FLIP
  JOURNAL   Nature 388 (6638), 190-195 (1997)
   PUBMED   9217161
REFERENCE   10 (bases 1 to 14612)
  AUTHORS   Shu,H.B., Halpin,D.R. and Goeddel,D.V.
  TITLE     Casper is a FADD- and caspase-related inducer of apoptosis
  JOURNAL   Immunity 6 (6), 751-763 (1997)
   PUBMED   9208847
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC007283.3.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_003879.6.
            
            Summary: The protein encoded by this gene is a regulator of
            apoptosis and is structurally similar to caspase-8. However, the
            encoded protein lacks caspase activity and appears to be itself
            cleaved into two peptides by caspase-8. Several transcript variants
            encoding different isoforms have been found for this gene, and
            partial evidence for several more variants exists. [provided by
            RefSeq, Feb 2011].
            
            Transcript Variant: This variant (1) represents use of an alternate
            first exon and encodes the longest protein isoform (1). Variants 1
            and 2 both encode the same isoform (1).
            
            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 :: SRR1803613.216584.1,
                                           SRR1803611.269629.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000309955.8/ ENSP00000312455.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-318               AC007283.3         120039-120356       c
            319-736             AC007283.3         106374-106791       c
            737-842             AC007283.3         103386-103491       c
            843-978             AC007283.3         100413-100548       c
            979-1061            AC007283.3         96081-96163         c
            1062-1116           AC007283.3         91088-91142         c
            1117-1166           AC007283.3         87468-87517         c
            1167-1248           AC007283.3         86685-86766         c
            1249-1759           AC007283.3         75578-76088         c
            1760-14612          AC007283.3         59833-72685         c
FEATURES             Location/Qualifiers
     source          1..14612
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q33.1"
     gene            1..14612
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="CASP8 and FADD like apoptosis regulator"
                     /db_xref="GeneID:8837"
                     /db_xref="HGNC:HGNC:1876"
                     /db_xref="MIM:603599"
     exon            1..318
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /inference="alignment:Splign:2.1.0"
     exon            319..736
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /inference="alignment:Splign:2.1.0"
     CDS             456..1898
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="isoform 1 is encoded by transcript variant 1;
                     inhibitor of FLICE; caspase-related inducer of apoptosis;
                     usurpin beta; caspase homolog; caspase-eight-related
                     protein; MACH-related inducer of toxicity; FADD-like
                     antiapoptotic molecule 1; cellular FLICE-like inhibitory
                     protein; caspase-like apoptosis regulatory protein; testis
                     secretory sperm-binding protein Li 233m"
                     /codon_start=1
                     /product="CASP8 and FADD-like apoptosis regulator isoform
                     1"
                     /protein_id="NP_003870.4"
                     /db_xref="CCDS:CCDS2337.1"
                     /db_xref="GeneID:8837"
                     /db_xref="HGNC:HGNC:1876"
                     /db_xref="MIM:603599"
                     /translation="MSAEVIHQVEEALDTDEKEMLLFLCRDVAIDVVPPNVRDLLDIL
                     RERGKLSVGDLAELLYRVRRFDLLKRILKMDRKAVETHLLRNPHLVSDYRVLMAEIGE
                     DLDKSDVSSLIFLMKDYMGRGKISKEKSFLDLVVELEKLNLVAPDQLDLLEKCLKNIH
                     RIDLKTKIQKYKQSVQGAGTSYRNVLQAAIQKSLKDPSNNFRLHNGRSKEQRLKEQLG
                     AQQEPVKKSIQESEAFLPQSIPEERYKMKSKPLGICLIIDCIGNETELLRDTFTSLGY
                     EVQKFLHLSMHGISQILGQFACMPEHRDYDSFVCVLVSRGGSQSVYGVDQTHSGLPLH
                     HIRRMFMGDSCPYLAGKPKMFFIQNYVVSEGQLEDSSLLEVDGPAMKNVEFKAQKRGL
                     CTVHREADFFWSLCTADMSLLEQSHSSPSLYLQCLSQKLRQERKRPLLDLHIELNGYM
                     YDWNSRVSAKEKYYVWLQHTLRKKLILSYT"
     exon            737..842
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /inference="alignment:Splign:2.1.0"
     exon            843..978
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /inference="alignment:Splign:2.1.0"
     exon            979..1061
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /inference="alignment:Splign:2.1.0"
     exon            1062..1116
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /inference="alignment:Splign:2.1.0"
     exon            1117..1166
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /inference="alignment:Splign:2.1.0"
     exon            1167..1248
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /inference="alignment:Splign:2.1.0"
     exon            1249..1759
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /inference="alignment:Splign:2.1.0"
     exon            1760..14612
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /inference="alignment:Splign:2.1.0"
     polyA_site      7096
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="major polyA site"
     regulatory      7672..7677
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="hexamer: AACAAA"
     polyA_site      7693
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="major polyA site"
     regulatory      9639..9644
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="hexamer: AATAAA"
     polyA_site      9661
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
     regulatory      10574..10579
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="hexamer: AATAAA"
     polyA_site      10609
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="major polyA site"
     polyA_site      12179
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
     regulatory      12251..12256
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="hexamer: CATAAA"
     polyA_site      12277
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
     regulatory      13557..13562
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="hexamer: AATAAA"
     polyA_site      13585
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
     regulatory      14588..14593
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
                     /note="hexamer: ATTAAA"
     polyA_site      14612
                     /gene="CFLAR"
                     /gene_synonym="c-FLIP; c-FLIPL; c-FLIPR; c-FLIPS; CASH;
                     CASP8AP1; Casper; cFLIP; CLARP; FLAME; FLAME-1; FLAME1;
                     FLIP; I-FLICE; MRIT"
ORIGIN      
        1 acacaagcca tagcaggaaa cagcgagctt gcagcctcac cgacgagtct caactaaaag
       61 ggactcccgg agctaggggt ggggactcgg cctcacacag tgagtgccgg ctattggact
      121 tttgtccagt gacagctgag acaacaagga ccacgggagg aggtgtagga gagaagcgcc
      181 gcgaacagcg atcgcccagc accaagtccg cttccaggct ttcggtttct ttgcctccat
      241 cttgggtgcg ccttcccggc gtctagggga gcgaaggctg aggtggcagc ggcaggagag
      301 tccggccgcg acaggacgaa ctcccccact ggaaaggatt ctgaaagaaa tgaagtcagc
      361 cctcagaaat gaagttgact gcctgctggc tttctgttga ctggcccgga gctgtactgc
      421 aagacccttg tgagcttccc tagtctaaga gtaggatgtc tgctgaagtc atccatcagg
      481 ttgaagaagc acttgataca gatgagaagg agatgctgct ctttttgtgc cgggatgttg
      541 ctatagatgt ggttccacct aatgtcaggg accttctgga tattttacgg gaaagaggta
      601 agctgtctgt cggggacttg gctgaactgc tctacagagt gaggcgattt gacctgctca
      661 aacgtatctt gaagatggac agaaaagctg tggagaccca cctgctcagg aaccctcacc
      721 ttgtttcgga ctatagagtg ctgatggcag agattggtga ggatttggat aaatctgatg
      781 tgtcctcatt aattttcctc atgaaggatt acatgggccg aggcaagata agcaaggaga
      841 agagtttctt ggaccttgtg gttgagttgg agaaactaaa tctggttgcc ccagatcaac
      901 tggatttatt agaaaaatgc ctaaagaaca tccacagaat agacctgaag acaaaaatcc
      961 agaagtacaa gcagtctgtt caaggagcag ggacaagtta caggaatgtt ctccaagcag
     1021 caatccaaaa gagtctcaag gatccttcaa ataacttcag gctccataat gggagaagta
     1081 aagaacaaag acttaaggaa cagcttggcg ctcaacaaga accagtgaag aaatccattc
     1141 aggaatcaga agcttttttg cctcagagca tacctgaaga gagatacaag atgaagagca
     1201 agcccctagg aatctgcctg ataatcgatt gcattggcaa tgagacagag cttcttcgag
     1261 acaccttcac ttccctgggc tatgaagtcc agaaattctt gcatctcagt atgcatggta
     1321 tatcccagat tcttggccaa tttgcctgta tgcccgagca ccgagactac gacagctttg
     1381 tgtgtgtcct ggtgagccga ggaggctccc agagtgtgta tggtgtggat cagactcact
     1441 cagggctccc cctgcatcac atcaggagga tgttcatggg agattcatgc ccttatctag
     1501 cagggaagcc aaagatgttt tttattcaga actatgtggt gtcagagggc cagctggagg
     1561 acagcagcct cttggaggtg gatgggccag cgatgaagaa tgtggaattc aaggctcaga
     1621 agcgagggct gtgcacagtt caccgagaag ctgacttctt ctggagcctg tgtactgcgg
     1681 acatgtccct gctggagcag tctcacagct caccatccct gtacctgcag tgcctctccc
     1741 agaaactgag acaagaaaga aaacgcccac tcctggatct tcacattgaa ctcaatggct
     1801 acatgtatga ttggaacagc agagtttctg ccaaggagaa atattatgtc tggctgcagc
     1861 acactctgag aaagaaactt atcctctcct acacataaga aaccaaaagg ctgggcgtag
     1921 tggctcacac ctgtaatccc agcactttgg gaggccaagg agggcagatc acttcaggtc
     1981 aggagttcga gaccagcctg gccaacatgg taaacgctgt ccctagtaaa aatacaaaaa
     2041 ttagctgggt gtgggtgtgg gtacctgtat tcccagttac ttgggaggct gaggtgggag
     2101 gatcttttga acccaggagt tcagggtcat agcatgctgt gattgtgcct acgaatagcc
     2161 actgcatacc aacctgggca atatagcaag atcccatctc tttaaaaaaa aaaaaaaagg
     2221 acaggaacta tcttactcaa tgtattagtc atgtttctct agagggacag aactaatagg
     2281 atacatgtat ataaaaaggg gagtttatta aggagtattg actcacatga tcacagggtt
     2341 aggtcccaca ataggtcatc tgcaagcaag gaagccaatt caagtcccaa agctgaagaa
     2401 cttggagtcc aatgtttgag ggcaggaagc attcagcatg agagaaagat ggaggccaga
     2461 agactacacc agtctagtct ttccatgttt tgcctgcttt tattctggca gtgctggcag
     2521 ctgattagat ggtgcccacc cagattgagg atggtctgcc tttcccagtc cactgactca
     2581 aatgttaaat ctcctttggc agcaccctca cagatgtacc cgggaacact ttgcatcctt
     2641 ctattcaatc aagttgatac tcagtattaa ccatcacagt ccatttgggc aactatacca
     2701 aattaccata gaccaggtga cttaaacagc agttatttct cacagttccg gaggctggga
     2761 aatccaacat ctaagtggta gcatatctgg tgtctggtaa ggcatgcttc cagatcttac
     2821 cagatgtcag tcttttgatg ttctcacatg gcagaaaaag aggatgcaaa ctctcaagta
     2881 tatctttaag ggcacaaatt ccattcatga gggctctacc ctcatcacct aattacctcc
     2941 caaaggcccc accttctgat actgtcactt tggggatact gtctcccctt tgaattctgg
     3001 ggggaataca aacattcagt ttgtaacaat agccttatga tttagaggtt acttgttcat
     3061 tcacctagac ctcaaattgc attttacagc tagtcaagta tatctttctc tgatttgata
     3121 gtgtgaccta aaaggggacc attgtttgaa atatcattag agttgcttat tattattatt
     3181 attattatta ttattattat tattattatt attgagacag agtttcattc tgctgcccag
     3241 gctggagtgc agtggcatca tcttggctca ttgcaacctc tgccttctgg gttcaagcga
     3301 ttctcctgcc tcagcctccc gagtagctgg gattacaggc tcctgccacc acacccggct
     3361 aatttttgta tttttagtgg agacagggtt tccaccatgt tggccagcgt ggtcttgaac
     3421 tcctgacctc aggtgattca ccagcctcgg cctcccaaag tgctgggatt acaggtgtga
     3481 gccactgcac ctggcctatt attattttta aatttttttt ttttaattga tcattcttgg
     3541 gtgtttctca cagagggtga tttggcaggg tcacaggaca atagtggagg gaaggtcagc
     3601 agataaacaa gtgaacaaag gtctctggtt ttcctaggca gaggaccctg cggccttccg
     3661 cagtgtttgt gtccctgggt acttgagatt agggagtggt gatgactctt aaggagcatg
     3721 ctgccttcaa gcatctgttt aacaaagcac atcttgcact gcccttaatc catttaaccc
     3781 tgagtggaca cagcacatgt ttcagagagc acagggttgg gggtaaggtc atagatcaac
     3841 agcatcctaa ggcagaagaa tttttcttag tacagaacaa aatgaagtct cccatgtcta
     3901 cttctttcta cacagacaca gcaacaatct gatttctcta tcttttcccc acctttcccc
     3961 cttttctatt ccacaaaacc gccatcgtca tcatggcctg ttctcaatga gctgttgggt
     4021 acacctccca gacggggtgg cggctgggca gaggggctcc tcacttccca gatggggcgg
     4081 ccaggcggac gcgcccccca cctccctccc ggacgggata gctggccggg cgggggctga
     4141 ccccccacct ccctccccga cggggcggct ggccgggcgg gggctgaccc ccacgcctcc
     4201 ctcccggacg gggcggctgc caggcggagg ggctcctcac ttctcagacg gggtggctgc
     4261 tgggcggaga cgctcctcac ttcccagaca gggtggctgt cgggcggagg ggctcctcac
     4321 ttctcagacg gggcagctgc gggcggaggg gctcctcact tctcagacgg ggtggccggg
     4381 cagagaagct cctcacatcc cagacggggg ggcggggcag aggcgctccc cacatctcag
     4441 acgatgggcg gccgggcaga gacgctcctc acttcatccc agacggggtg gcggccgggc
     4501 agaagctgta atctcggcac cctggggggc caaggcaggc ggctgggagg cggaggccgt
     4561 agccagctga gatcacacca ctgcactcca gcctgggcaa cattgagcac tgagtggacg
     4621 agactctgcc cgcaatcccg gcacctcggg aggccgaggc tggcagatca ctcgcagtca
     4681 ggagctggag accagcccgg ccaacacagt gaaaccctgt ctccaccaaa aaaatacgaa
     4741 aaccagtcag gcgtggcggc gcccgcaatg gcaggcacgc ggcaggccga ggcgggagaa
     4801 tcaggcaggg aggctgcagt gagccgagat ggcagcagta cagtccagct tcggctcggc
     4861 atcagaggga gaccgtgggg agagggagaa gagagggagg gggagagggc tatttttaaa
     4921 attttttaaa attgctgaac aggggtacct ctgggcagtg tgtcagaata ccacttttta
     4981 aatattttat gatttattta tttttctatt tcttgaggtt ttaactgatg tgtatctgta
     5041 tgtctatttg tgtatatttt gtcatgatca tgtaacagag tctgaaaagt gtcgaagaga
     5101 cagttttcag gaacaacaag caattattcc tactttccaa gttattttga tgccatggtg
     5161 gctcatacct ataatctgag tactttggga ggctgaggtg gactgatcac ttgagcccag
     5221 gagtttgaga ccagcctggg caacatagca agactccatc tctacaaaaa aagacaaaat
     5281 ttagctgagc gtggtggcgt gttcctgtag tcccagctac ttgggaggct gaagtgagtg
     5341 gatcccctga gcccagagag gtcaaggttg tgatgagctg tgatcacacc actgcacttc
     5401 agcatgggag acagagtgag accctgtttc agaaaaaata aataaataaa accaccagca
     5461 ccacaaacaa caacaaaaag ttattttgta cttgttttga gcacaggact cctgagggta
     5521 tctttgcatt taatattaca taggggtgcc agtgggaagt aatgtgtatg cttggcctca
     5581 tgagctaaaa ccctgtgtta attatgacag aaggaaagtg tgtgagagag atcttaacta
     5641 cctagcagct ctagctgcca tcttgaacca tgaagatacg ggccacacgt aggggtagct
     5701 gggtagtgag cagcaagaag ccttgttgga tgagggcacg aaggagcaga atcactggaa
     5761 tcactgtgtc agccctaatt acctacctct ggacttttat gtgaggggaa aaaaaattga
     5821 cagtttatat ttatctcaac ctagttaacc caagtgatgc attgttatga gattaaaatg
     5881 tttggaggcc gggtgcggtg gctcacgcct ataatcccag ccctttggga ggccaaggcg
     5941 ggcggatcac gaggtcagga gatcaagacc atcctggcta acatgtaaaa ccccgtctct
     6001 actaaaaata caaaaaatta gccaggcgtt gtggcggtcg cctgtagtcc ctgctatttg
     6061 ggaggccgag gcaagagaac ggcatgaacc tgggaggtgg agcttgcagc gagctgagat
     6121 cttgccactg cactccagcc tgggcgacag tgcgagactc tgtctcaaaa ataaataaat
     6181 aaataaataa taaataaaat gtttggaatg ttggcttcat ccctgggatg caaggctggt
     6241 tcaacatacg caaatcaaga aacataattc atcacataaa cagaactaaa gacaaaaacc
     6301 acatgattat ctcaatagat acagaaaagg ccttcaataa aattcaacgt tgcttcatgt
     6361 taaaaactct caataaacta ggtattgatg gaaaatatct caaaataata accatttatg
     6421 acaaacccac agccattatc atactgaatg ggcaaaagct ggaagcattc cccttgaaaa
     6481 ctggcacaag acagggatgc cgtctcacca ctcctattta acatagtatt ggaagttctg
     6541 gccaagaaaa tcaggcaaga gaaacaaata aggggtattc aaataggaaa agaggaagta
     6601 aaactgtgtt tgcagatgac atgatactat atctagaaaa ccccattatc tccacccaaa
     6661 agttccttaa gctgataagc aacttcagca aagtctcagg atacaaaatc aatgtgcaga
     6721 aatcacaagc attctataca ccaacaatac acaagcagag agccaaatca tgaatgaact
     6781 cccattcaca gttgctagaa agagaataaa atacctagga atacagctaa taagatgtga
     6841 aggatctctt caaggagaac tacaaaccac tgctcaagga aataagagag gacacaaatg
     6901 aaaaaacatt ccattctcgt ggataggaag aatcaatatc atgaaaatgg ccatactacc
     6961 caaagtaatt tataggttca ttgctattcc cattaaacta ctattgacat tcttcacaga
     7021 attagaaaaa aactacttta aaattcaaat ggaaccaaaa aagagcccgt ataaccaaga
     7081 caacaataag caaaaagaac aaagctggaa gcatcacact acccaacttc aaagtatact
     7141 gcaaggctac agtagccaaa atggcatggt actggtacaa aaacagacac atagaccaat
     7201 ggaacagaat agagaccaga gaaagaagac cacacatcta cagccatctg atcatcgaca
     7261 aacctgacaa aaacaagcaa tggggaaaag attccctatt taataaatgg tgctgggaaa
     7321 actggctagc catatgcaga aaattgaaac tgaccccttc cttacacctt atacaaaaat
     7381 taactcaaga ttaaagactt aatgtaaaac ctaaaactat aaaaacccta gaagaaaatc
     7441 tatttaatac cattcaagac ataggcacaa gcaaaggttt catgacaaaa acatcaaaag
     7501 caattgcaac aaaagcaaaa attacaaatg ggatctaatt aaactaaaga gctcctgcac
     7561 agcaaaagaa actatcatta gagtgaacag gcaacctaca gaatgggaga acatttttgc
     7621 aatctatcca tctgacaaag gtctaatatc cagaacctac aaggaactta aaacaaattt
     7681 acaaggaaaa aaacaacccc atcaaaaagt ggacaaagga catgaacaga cacttctcaa
     7741 aagaagacat ttatgtggcc aacaaacata taaaaaaaag ctcaacctta ctgatcatta
     7801 gagaaatgca aaggagaacc acaatgagat accatctcat gccggtcaga atggtgatta
     7861 ttaaaaagtc aaaaaacaac agatgctggc gaggctgtgg agaagtagga acacttttac
     7921 attgttggtg ggaatgtaaa ttagttcaac cgttgtggaa gtgtgtgtgg ctattcctca
     7981 aagatctaga actagaaata ctatttgtcc cagcaatccc attactgggt atatacccaa
     8041 aggaatataa accattttat tataaagata catgcacatt tttgttcatt gcagcactct
     8101 tcacaatagc aaagacacaa tagcaaatgc ccatcaaaga tagactggat aaagaaaatg
     8161 tggtacatat acaccatgga atactgtgca gtgcagccat tacagctttt ggtgatacag
     8221 tgaatcagat ttttcattaa ttcttttaat tggttattac tgaacgtgaa aaagtaatgt
     8281 ttgtattgaa atcttgagtc tggccatgtt tctattttaa attcataaag aattctaaca
     8341 agaggaattc caagaatgtc ataaatggat gtttctccat ggatgaagga actgttttat
     8401 tcacttgctg ataattcagc ctaatccagt ttgacatcat atagataagt agttgaatta
     8461 tggatttaaa atacatatca ttttctaact ccaaaggtaa tacttattta aatggttttg
     8521 aaaatataga aaggcacaat ttctttttaa atctgttatt ctccaccacc actcaatctg
     8581 tctatcatct atctctccat tcattcttcc atttgtttat atctgttaat ctttgtatgt
     8641 gttcatgtat agcttttaca tgattggaat cataatgcat attccatttt gaagtctgct
     8701 tttttttaca caaaaatatg ttgtgaatat tttcctatat tatgaaatat cattagctga
     8761 gcttttagaa ttgactgcat gttttggtac catttagata tagtttaaga tacttagaag
     8821 ttatgtggct ttgccactat ggatgaatct tatttactca atattaatta cttacaaata
     8881 acctcaccta aacactactc agccataaaa aggaatgaat taatgacatt cacagcaacc
     8941 tggagactat tactctaaag gaagtaactg aggaatggaa aaccaaacat tgtatgttct
     9001 cactcataag tgggagataa gctatgagga tgcaaaggca taagaaggat acaatggact
     9061 ttggggactt aggggaaagg gtgggagggg ggtgaaggat aaaagaatac aaattgggtt
     9121 cagtgtatac tgctcaggtg atgggtgcac cagaatctca caagtaacca cttaattact
     9181 tacgcatgta accagatacc acctgttccc caaacaccta tggaaataat tttgtttttt
     9241 tttttaaaaa aggaatgaga tcatgtcctt tgcagggaca tggatgaagc tggaagccat
     9301 tatcctcagc aaactaacag aggagcagga aaccaaacac cacatgttct cacttgtaag
     9361 cggaagctga acaatgagaa cacacggaca cagggatgag atcaacacac actggggcct
     9421 gatgcagggg ccgtagcggg gagagcatca ggataactag ctaatgcatg tggggcttaa
     9481 tacctaggtg ataggttgat aggtgcagca aaccaccatg ggacacgttt acctatgtaa
     9541 caaacccgca catcctgcac ttgtatccag aacttaaaat attttaaaaa tctttagaga
     9601 atacaaaaaa aaaaaaaaag attcttcaat gcatacacaa taaaattgca gttcagtcaa
     9661 acattggaag tctttctctg actgtctagt tggtatcttc attttcagct tcttcaagat
     9721 cccactccaa acactgttag ctcagccaaa ttgaacagct catatctcct acctctggat
     9781 ctttggttct ggtgattgta tatttctgga ccatctggaa ccccagcata tcaccctacc
     9841 ccacatctcc acatccccaa aatataacca tacttcaagg gcagttcaaa taccatctcc
     9901 ttctatcctc catgaagtca gttatctctt ccattggaat tatcgccccc tctcctgaac
     9961 agtactattt cgtgtgaatc tcctccaagc cttcttttca ttttatatct catgctgtaa
    10021 ttcttggaaa gtatgctgta gctcaagtgc agaattctca tcagttttat ctttatatct
    10081 ctcctaaaca ctttacctga tgaagagcct ggcatacaca taaatatata ttgaatgaat
    10141 cagtgatgga ttgaaaagag aaatgatgga tctcctaaat tttaactttt ataaaatatt
    10201 ttgatacatt catgacctta ctttagcaag caatgaacgt gatgtaaact attgttgata
    10261 tagtttttat attggaagtg taagtagttt gtggcatggg attgtgacat atcctaggtt
    10321 tcctcatctt ctttttattg aaatgtaatt cacaagccat aaaatttgcc cctttaaagt
    10381 aaatgatgca gtggatttta gtatatttac agagttgtgc aatcatcacc actatctaat
    10441 tccagaacat ttccatctac ctagaaactc cataccagtg agctgccact ctaatcctcc
    10501 tcttccccca gcctctagaa acaataatcc attttctgtc tctatgattt gcctgttcta
    10561 gatattttat aaaaataaac atgtggcctt tcgtgtctga cttccttcac ttagcatgtt
    10621 tcaaggttca tctatgctat agagtgtacc agtgcttcat tacattttat ggctgaataa
    10681 taccctattg tgtggatata ccgcatttag tttattcatc agttgatcga aatttagact
    10741 gtttccactt ttttgctatt atggatgatg ctgctatgaa tattcgtata tgaattttta
    10801 tatggatata tgttttcagt tcttctgggc atatacctta gaagtgagag tgctcatcat
    10861 atagtaactc tatgtttagc cttttgagga actgccaaac tgcttttcaa agtagtagca
    10921 tcattttata ttcccaccag cagtgtatga ggtttttttt atttttttgt ttttgagacg
    10981 gagtctcact ctgtcgccca gggtggagtg cagtggcgtt atcttgattc actgtaacct
    11041 ctgccttctg ggttcaagcc attctcctgc ctcagcctcc ctagtagttg ggagtagctg
    11101 ggtttacagg agctcgccac catgcccaac taatttttgt attgtttttt gagacggagt
    11161 ctcgctctgt ggcccaggct ggagtgcagt ggtgcaatct cagctcactg caagctccgc
    11221 ctcctgggtt catgccattc tcctgcctca gcctcccaag tatctgggac tacagccgcc
    11281 ctccaccacg cccggctaat tttttgtatt tttagtagag acagggtttc accgtgttag
    11341 ccaggatggt ctctatctcc tgacctcgtg atccgcctgc cttggcctcc caaagtgctg
    11401 ggattacagg cgtgagccac cgcgcccagc caatttttgt atttttagta aagacagggt
    11461 ttcaccatgt tggccaggct ggtctcgaac tcctggcctc aggtgatctg actgccttgg
    11521 cttcccaaag tgctggcatt acagacatta gctactgtgc ctggcctcaa gtcctttctc
    11581 attttaaaac tgcgttattt tattttattt ttctgagatg gaatctcact ctgtcgccca
    11641 ggttggagtg cagtggtgca atctcggctc actgcaacct ccacctcctg agttcaagcg
    11701 actctcctgc ctcggcctcc ctagtaactg ggattacagg cacccaccat cacgcctggc
    11761 taatttttgt atttttagta gagacagggt ttcgccatgt tggccaggct ggtcttgaac
    11821 tcctgaactc aggtgatctg cctgcctcgg cctcccaaaa tgctaggatt acaggcgtga
    11881 gccaccacac ccggtgggtt gtctttttat tgttgagttg taagcattct ttttaatatt
    11941 ctggatacta gtttcttatc aggtacaatc tttgtgaata tattctccca ttccatggat
    12001 tgtcttctca ctttctggat actatacagt acaagtttta aattttgatg aagttcactt
    12061 gatttctgtt ttttatgtta ttgcttatgc ttttggtgtc atacctaaaa aaccattgtc
    12121 taaatcaatt gcctatgagg tgttacccct atgttttctt ctaaagtttt atgattttag
    12181 ctctttgacc cattttgagt tatttttgtg tatgcagtgc gagataagca tccagcctca
    12241 ttcttttgca cataaatgtt cacttgtctt agcattactt attgaaaata ctattttttc
    12301 cctatagaat tattttatac ttatcacaaa tcaactaact ataagggttt atttctggac
    12361 tcaattctgt tgctctatct tatggtagta ccacactgtc ttgattattg taacttcgta
    12421 gtaagttttg gaatccagaa atgtagtcct ctaactttgt tgttgttgtt gttcttcttt
    12481 tttcttttgt agagatgagg ccttgctatg ttgcccaggc tggtctcaaa ctcctggcct
    12541 caaacaatcc tcccacctcc acctcccaaa gtgctgaggg gtgagccact gcaactggcc
    12601 tgttcttttt caaaattgtt agggctgtat tgggtttacc tttccctaaa ttttcatata
    12661 actgttagga ttcacttgca aatttatgta aaaagggcct ctggaatttt gatagtgatt
    12721 acactgaatg agaggagttt ggcaggactg gtttcccaag accacaagac cctgtaagac
    12781 cctgctgata agacaggatg tggtagaaag gccaacccaa accagccaaa accatgatgg
    12841 tgacagaaga gacctctggt tacctttgct gcccattcta tggtaattat aatacattag
    12901 cacgctaaaa gaaacttcta cagcaccatg atagtttaca actgccatag caactttcag
    12961 aagttaccct gtatggtcta aaaggtccag acctccccac ttctttcctg gaaaactcat
    13021 gaataagcca cctcttgttt agcgtatagt caagaagcaa ccataaatat agccagtcag
    13081 cagcccatca gggctactct tcctatgggg tagccattct tttattcctt tactttctta
    13141 atgaacttgc tttcacttta ttctgtcagc atgctcttga attctttcct gaacccactt
    13201 gacctcttgg gctgagcctt aaccttgggg tacttttgcc tataacaaac atacaaagat
    13261 aagtttggct gggcgcagtg gctcatgcct gtaatcccag gactttggga ggctgaggat
    13321 ggtggatcgc ttgagccaag gaatttgagg ccaccttggg caacacggca aaaccctgtc
    13381 tctactaaaa atacaaaaat tagctgggta tggtagcatg cgcctgtagt accagctact
    13441 cggaaggctg aggtgggagg atcacttgag cccgggaggt ggaggtttca gtgagctgag
    13501 attgtgccac tgtactccag cctggggaac agagtgagac cctgtctcaa aataaaaata
    13561 aatttgaggt gtattgccat cttaacggaa gttgttactg gtggacggta tccaagttac
    13621 tggtggtaaa tctgcagcaa cctcaattct ttcctcctca gaagaaagaa tttgactgag
    13681 gggcataagg cagaaggagg gaccgaggca agtttcagag caacagtgaa agtttattac
    13741 gctttaggct gggcacagtg gctcatgcct gtaatcccag cattttggga ggctgaggca
    13801 ggtggattac ttgaggtcag tagttcgaga ccagcctggc catcatgatg atgaaacctc
    13861 gtctctacta aaaatagaaa aatcagctgg gcatggtggt ccatgcctct aatcccagct
    13921 actcgggagg ctgaggcagg cgaatcagtt gaacctggga ggcggaggtt gcagtgagcc
    13981 aagaaagttt attaagcttt agaacagtaa ggaaaggaaa gaaaagaagg aaagtataac
    14041 ttggaagagg gccaagcagg tgacctgaga aaccaggtgc agggcttgcc ctcttgactt
    14101 ggggttttat atgctggcat acttccggga tcttgtgtta cttttcccca ctcctgagat
    14161 ctttttgaga agctgatgat cagtctcagg tgttttctat tgcggggggg gggggcgggc
    14221 gggggagctg cctgtccctg gcaccacctg tgaccaatta ttactttaca gaaacattta
    14281 acaaccgcct gaccatcacc tgatggttgc ccaacactct tggtgtgtgt cgggggagcc
    14341 ctctcctgcc ttgctcagac ctgaatgtac ccattgtaac aaaccccttc tttgtatact
    14401 ttgatatggt gacatttctt gtcacttgcc tcattgtgaa tttttataga tgtggctaag
    14461 tcatatgctt ccttctgaaa aattatgtca aatactagca gtttctcact gttttttgcc
    14521 ctagaaacaa caaactaacc ttgaagtgaa aggcctttct gcgtttatct tacctttttt
    14581 gagcagcatt aaaactgttt tactcagacc aa
//
