LOCUS       NM_020340              14859 bp    mRNA    linear   PRI 01-AUG-2024
DEFINITION  Homo sapiens ARFGEF family member 3 (ARFGEF3), mRNA.
ACCESSION   NM_020340
VERSION     NM_020340.5
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 14859)
  AUTHORS   Toki,S., Yoshimaru,T., Matsushita,Y., Aihara,H., Ono,M.,
            Tsuneyama,K., Sairyo,K. and Katagiri,T.
  TITLE     The survival and proliferation of osteosarcoma cells are dependent
            on the mitochondrial BIG3-PHB2 complex formation
  JOURNAL   Cancer Sci 112 (10), 4208-4219 (2021)
   PUBMED   34363714
  REMARK    GeneRIF: The survival and proliferation of osteosarcoma cells are
            dependent on the mitochondrial BIG3-PHB2 complex formation.
REFERENCE   2  (bases 1 to 14859)
  AUTHORS   Chigira,T., Nagatoishi,S., Takeda,H., Yoshimaru,T., Katagiri,T. and
            Tsumoto,K.
  TITLE     Biophysical characterization of the breast cancer-related BIG3-PHB2
            interaction: Effect of non-conserved loop region of BIG3 on the
            structure and the interaction
  JOURNAL   Biochem Biophys Res Commun 518 (1), 183-189 (2019)
   PUBMED   31421830
  REMARK    GeneRIF: These results establish a model for the BIG3-PHB2
            interaction and an entry for drug discovery for breast cancer.
REFERENCE   3  (bases 1 to 14859)
  AUTHORS   Liu,T., Li,H., Hong,W. and Han,W.
  TITLE     Brefeldin A-inhibited guanine nucleotide exchange protein 3 is
            localized in lysosomes and regulates GABA signaling in hippocampal
            neurons
  JOURNAL   J Neurochem 139 (5), 748-756 (2016)
   PUBMED   27696409
REFERENCE   4  (bases 1 to 14859)
  AUTHORS   Chen,Y.A., Murakami,Y., Ahmad,S., Yoshimaru,T., Katagiri,T. and
            Mizuguchi,K.
  TITLE     Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3)
            is predicted to interact with its partner through an ARM-type
            alpha-helical structure
  JOURNAL   BMC Res Notes 7, 435 (2014)
   PUBMED   24997568
  REMARK    GeneRIF: BIG3 (ARFGEF3) is predicted to interact with its partner
            PHB2 through an ARM-type alpha-helical structure.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 14859)
  AUTHORS   Kim,J.W., Akiyama,M., Park,J.H., Lin,M.L., Shimo,A., Ueki,T.,
            Daigo,Y., Tsunoda,T., Nishidate,T., Nakamura,Y. and Katagiri,T.
  TITLE     Activation of an estrogen/estrogen receptor signaling by BIG3
            through its inhibitory effect on nuclear transport of PHB2/REA in
            breast cancer
  JOURNAL   Cancer Sci 100 (8), 1468-1478 (2009)
   PUBMED   19496786
REFERENCE   6  (bases 1 to 14859)
  AUTHORS   Hendrickx,A., Beullens,M., Ceulemans,H., Den Abt,T., Van Eynde,A.,
            Nicolaescu,E., Lesage,B. and Bollen,M.
  TITLE     Docking motif-guided mapping of the interactome of protein
            phosphatase-1
  JOURNAL   Chem Biol 16 (4), 365-371 (2009)
   PUBMED   19389623
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AB252196.1 and BU682567.1.
            
            On Nov 23, 2018 this sequence version replaced NM_020340.4.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AB252196.1, SRR1803615.60364.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1968832
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000251691.5/ ENSP00000251691.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-14829             AB252196.1         24-14852
            14830-14859         BU682567.1         14-43               c
FEATURES             Location/Qualifiers
     source          1..14859
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q23.3-q24.1"
     gene            1..14859
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /note="ARFGEF family member 3"
                     /db_xref="GeneID:57221"
                     /db_xref="HGNC:HGNC:21213"
                     /db_xref="MIM:617411"
     exon            1..233
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     CDS             149..6682
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /note="protein phosphatase 1, regulatory subunit 33"
                     /codon_start=1
                     /product="brefeldin A-inhibited guanine
                     nucleotide-exchange protein 3"
                     /protein_id="NP_065073.3"
                     /db_xref="CCDS:CCDS5189.2"
                     /db_xref="GeneID:57221"
                     /db_xref="HGNC:HGNC:21213"
                     /db_xref="MIM:617411"
                     /translation="MEEILRKLQKEASGSKYKAIKESCTWALETLGGLDTIVKIPPHV
                     LREKCLLPLQLALESKNVKLAQHALAGMQKLLSEERFVSMETDSDEKQLLNQILNAVK
                     VTPSLNEDLQVEVMKVLLCITYTPTFDLNGSAVLKIAEVCIETYISSCHQRSINTAVR
                     ATLSQMLSDLTLQLRQRQENTIIENPDVPQDFGNQGSTVESLCDDVVSVLTVLCEKLQ
                     AAINDSQQLQLLYLECILSVLSSSSSSMHLHRRFTDLIWKNLCPALIVILGNPIHDKT
                     ITSAHTSSTSTSLESDSASPGVSDHGRGSGCSCTAPALSGPVARTIYYIAAELVRLVG
                     SVDSMKPVLQSLYHRVLLYPPPQHRVEAIKIMKEILGSPQRLCDLAGPSSTESESRKR
                     SISKRKSHLDLLKLIMDGMTEACIKGGIEACYAAVSCVCTLLGALDELSQGKGLSEGQ
                     VQLLLLRLEELKDGAEWSRDSMEINEADFRWQRRVLSSEHTPWESGNERSLDISISVT
                     TDTGQTTLEGELGQTTPEDHSGNHKNSLKSPAIPEGKETLSKVLETEAVDQPDVVQRS
                     HTVPYPDITNFLSVDCRTRSYGSRYSESNFSVDDQDLSRTEFDSCDQYSMAAEKDSGR
                     SDVSDIGSDNCSLADEEQTPRDCLGHRSLRTAALSLKLLKNQEADQHSARLFIQSLEG
                     LLPRLLSLSNVEEVDTALQNFASTFCSGMMHSPGFDGNSSLSFQMLMNADSLYTAAHC
                     ALLLNLKLSHGDYYRKRPTLAPGVMKDFMKQVQTSGVLMVFSQAWIEELYHQVLDRNM
                     LGEAGYWGSPEDNSLPLITMLTDIDGLESSAIGGQLMASAATESPFAQSRRIDDSTVA
                     GVAFARYILVGCWKNLIDTLSTPLTGRMAGSSKGLAFILGAEGIKEQNQKERDAICMS
                     LDGLRKAARLSCALGVAANCASALAQMAAASCVQEEKEEREAQEPSDAITQVKLKVEQ
                     KLEQIGKVQGVWLHTAHVLCMEAILSVGLEMGSHNPDCWPHVFRVCEYVGTLEHNHFS
                     DGASQPPLTISQPQKATGSAGLLGDPECEGSPPEHSPEQGRSLSTAPVVQPLSIQDLV
                     REGSRGRASDFRGGSLMSGSSAAKVVLTLSTQADRLFEDATDKLNLMALGGFLYQLKK
                     ASQSQLFHSVTDTVDYSLAMPGEVKSTQDRKSALHLFRLGNAMLRIVRSKARPLLHVM
                     RCWSLVAPHLVEAACHKERHVSQKAVSFIHDILTEVLTDWNEPPHFHFNEALFRPFER
                     IMQLELCDEDVQDQVVTSIGELVEVCSTQIQSGWRPLFSALETVHGGNKSEMKEYLVG
                     DYSMGKGQAPVFDVFEAFLNTDNIQVFANAATSYIMCLMKFVKGLGEVDCKEIGDCAP
                     APGAPSTDLCLPALDYLRRCSQLLAKIYKMPLKPIFLSGRLAGLPRRLQEQSASSEDG
                     IESVLSDFDDDTGLIEVWIILLEQLTAAVSNCPRQHQPPTLDLLFELLRDVTKTPGPG
                     FGIYAVVHLLLPVMSVWLRRSHKDHSYWDMASANFKHAIGLSCELVVEHIQSFLHSDI
                     RYESMINTMLKDLFELLVACVAKPTETISRVGCSCIRYVLVTAGPVFTEEMWRLACCA
                     LQDAFSATLKPVKDLLGCFHSGTESFSGEGCQVRVAAPSSSPSAEAEYWRIRAMAQQV
                     FMLDTQCSPKTPNNFDHAQSCQLIIELPPDEKPNGHTKKSVSFREIVVSLLSHQVLLQ
                     NLYDILLEEFVKGPSPGEEKTIQVPEAKLAGFLRYISMQNLAVIFDLLLDSYRTAREF
                     DTSPGLKCLLKKVSGIGGAANLYRQSAMSFNIYFHALVCAVLTNQETITAEQVKKVLF
                     EDDERSTDSSQQCSSEDEDIFEETAQVSPPRGKEKRQWRARMPLLSVQPVSNADWVWL
                     VKRLHKLCMELCNNYIQMHLDLENCMEEPPIFKGDPFFILPSFQSESSTPSTGGFSGK
                     ETPSEDDRSQSREHMGESLSLKAGGGDLLLPPSPKVEKKDPSRKKEWWENAGNKIYTM
                     AADKTISKLMTEYKKRKQQHNLSAFPKEVKVEKKGEPLGPRGQDSPLLQRPQHLMDQG
                     QMRHSFSAGPELLRQDKRPRSGSTGSSLSVSVRDAEAQIQAWTNMVLTVLNQIQILPD
                     QTFTALQPAVFPCISQLTCHVTDIRVRQAVREWLGRVGRVYDIIV"
     exon            234..285
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            286..367
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            368..499
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            500..568
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            569..691
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            692..734
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            735..813
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            814..918
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            919..1252
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            1253..1365
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            1366..2276
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            2277..2443
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            2444..2609
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            2610..2717
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            2718..2933
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            2934..3044
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            3045..3195
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            3196..3516
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            3517..3650
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            3651..3796
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            3797..3976
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            3977..4121
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            4122..4244
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            4245..4348
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            4349..4493
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            4494..4622
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            4623..4799
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            4800..4914
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            4915..5017
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            5018..5149
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            5150..5271
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            5272..6490
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     exon            6491..14859
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /inference="alignment:Splign:2.1.0"
     regulatory      10130..10135
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /note="hexamer: ATTAAA"
     polyA_site      10150
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /note="major polyA site"
     regulatory      14788..14793
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /note="hexamer: AATAAA"
     regulatory      14805..14810
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /note="hexamer: ATTAAA"
     polyA_site      14812
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /note="major polyA site"
     polyA_site      14826
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /note="major polyA site"
     regulatory      14842..14847
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
                     /note="hexamer: AATAAA"
     polyA_site      14859
                     /gene="ARFGEF3"
                     /gene_synonym="A7322; BIG3; C6orf92; dJ171N11.1; KIAA1244;
                     PPP1R33"
ORIGIN      
        1 gtgattcatc agcatccgcg ccggggcggc atgggggcgc gcgcggcggc cgcctaggcg
       61 cccagggcca ggcagcggcg gcttccccgg cccggctcgc ccgcgcttct ctccctgtgg
      121 gcggcggccc ggcgcctgga aggtcaagat ggaagaaatc ctgaggaagc tgcagaagga
      181 ggcgtccggg agcaagtaca aagccatcaa ggagagctgc acctgggccc tggaaactct
      241 aggtggtctg gataccattg tcaagatccc tccacatgta ctgagggaga aatgcctgct
      301 gcctctccag ttggctttgg aatccaagaa tgtgaagctg gcccaacatg ctttggcagg
      361 gatgcagaag cttctgtcgg aagagaggtt tgtatccatg gaaacagatt ctgatgagaa
      421 gcagctgctc aatcagatac tgaatgccgt gaaagtgacg ccttcgctca acgaggacct
      481 gcaggtggaa gtgatgaagg ttttactatg catcacctac acgccaacat ttgatctgaa
      541 tgggagtgcc gtgctgaaga tcgcggaggt gtgcattgag acgtacataa gcagctgtca
      601 ccagcgtagc ataaacactg ctgtgcgggc aactctcagt caaatgctga gtgacttgac
      661 tttacagtta cgacagaggc aggagaatac gataattgaa aacccagatg tcccacagga
      721 tttcgggaat caagggtcaa cagtagagtc cctctgtgat gatgttgtct ctgtactcac
      781 cgtcctgtgt gagaagctgc aagccgccat aaatgacagc cagcagctgc agcttctcta
      841 cctggagtgc atcctgtctg tgctcagcag ctcctcctcc tccatgcacc tgcacaggcg
      901 cttcacggac ctgatctgga aaaacctctg ccctgctctc atcgtgatct tggggaatcc
      961 aattcatgac aaaaccatca cctctgctca caccagcagc accagtacca gcctggagtc
     1021 ggactctgcg tctccgggag tgtctgacca cggccgagga tcaggctgct cctgcactgc
     1081 gccggccctg agcggacctg tggctcggac tatctattac atcgcagccg agctggtccg
     1141 gctggtgggg tctgtggact ccatgaagcc cgtgctccag tccctctacc accgagtgct
     1201 gctctacccc ccaccccagc accgggtgga agccatcaaa ataatgaaag agatacttgg
     1261 gagcccacag cgtctctgtg acttggcagg acccagctcc actgaatcag agtccagaaa
     1321 aagatcaatt tcaaaaagaa agtctcatct ggatctcctc aaactcatca tggatggcat
     1381 gaccgaagca tgcatcaagg gtggcatcga agcttgctat gcagccgtgt cctgtgtctg
     1441 caccttgctg ggtgccctgg atgagctcag ccaggggaag ggcttgagcg aaggtcaggt
     1501 gcaactgctg cttctgcgcc ttgaggagct gaaggatggg gctgagtgga gccgagattc
     1561 catggagatc aatgaggctg acttccgctg gcagcggcga gtgctgtcct cagaacacac
     1621 gccgtgggag tcagggaacg agaggagcct tgacatcagc atcagtgtca ccacagacac
     1681 aggccagacc actctcgagg gagagttggg tcagactaca cccgaggacc attcgggaaa
     1741 ccacaagaac agtctcaagt cgccagccat cccagagggt aaggagacgc tgagcaaagt
     1801 attggaaaca gaggcggtag accagccaga tgtcgtgcag agaagccaca cggtccctta
     1861 ccctgacata actaacttcc tgtcagtaga ctgcaggaca aggtcctatg gatctaggta
     1921 tagtgagagc aattttagcg ttgatgacca agacctttct aggacagagt ttgattcctg
     1981 tgatcagtac tctatggcag cagaaaagga ctcgggcagg tccgacgtgt cagacattgg
     2041 gtcggacaac tgttcactag ccgatgaaga gcagacaccc cgggactgcc taggccaccg
     2101 gtccctgcga actgccgccc tgtctctaaa actgctgaag aaccaggagg cggatcagca
     2161 cagcgccagg ctgttcatac agtccctgga aggcctcctc cctcggctcc tgtctctctc
     2221 caatgtagag gaggtggaca ccgctctgca gaactttgcc tctactttct gctcaggcat
     2281 gatgcactct cctggctttg acgggaatag cagcctcagc ttccagatgc tgatgaacgc
     2341 agacagcctc tacacagctg cacactgcgc cctgctcctc aacctgaagc tctcccacgg
     2401 tgactactac aggaagcggc cgaccctggc gccaggcgtg atgaaggact tcatgaagca
     2461 ggtgcagacc agcggcgtgc tgatggtctt ctctcaggcc tggattgagg agctctacca
     2521 tcaggtgctc gacaggaaca tgcttggaga ggctggctat tggggcagcc cagaagataa
     2581 cagccttccc ctcatcacaa tgctgaccga tattgacggc ttagagagca gtgccattgg
     2641 tggccagctg atggcctcgg ctgctacaga gtctcctttc gcccagagca ggagaattga
     2701 tgactccaca gtggcaggcg tggcatttgc tcgctatatt ctggtgggct gctggaagaa
     2761 cttgatcgat actttatcaa ccccactgac tggtcgaatg gcggggagct ccaaagggct
     2821 ggccttcatt ctgggagctg aaggcatcaa agagcagaac cagaaggagc gggacgccat
     2881 ctgcatgagc ctcgacgggc tgcggaaagc cgcacggctg agctgcgctc taggcgttgc
     2941 tgctaactgc gcctcagccc ttgcccagat ggcagctgcc tcctgtgtcc aagaagaaaa
     3001 agaagagagg gaggcccaag aacccagtga tgccatcaca caagtgaaac taaaagtgga
     3061 gcagaaactg gagcagattg ggaaggtgca gggggtgtgg ctgcacactg cccacgtctt
     3121 gtgcatggag gccatcctca gcgtaggcct ggagatggga agccacaacc cggactgctg
     3181 gccacacgtg ttcagggtgt gtgaatacgt gggcaccctg gagcacaacc acttcagcga
     3241 tggtgcctcg cagccccctc tgaccatcag ccagccccag aaggccactg gaagcgctgg
     3301 cctccttggg gaccccgagt gtgagggctc gccccccgag cacagcccgg agcaggggcg
     3361 ctccctgagc acggcccctg tcgtccagcc cctgtccatc caggacctcg tccgggaagg
     3421 cagccggggt cgggcctccg acttccgcgg cgggagcctc atgagcggga gcagcgcggc
     3481 caaggtggtg ctcaccctct ccacgcaagc cgacaggctc tttgaagatg ctacggataa
     3541 gttgaacctc atggccttgg gaggttttct ttaccagctg aagaaagcat cgcagtctca
     3601 gcttttccat tctgttacag atacagttga ttactctctg gcaatgccag gagaagttaa
     3661 atccactcaa gaccgaaaaa gcgccctcca cctgttccgc ctggggaatg ccatgctgag
     3721 gattgtgcgg agcaaagcac ggcccctgct ccacgtgatg cgctgctgga gccttgtggc
     3781 cccacacctg gtggaggctg cttgccataa ggaaagacat gtgtctcaga aggctgtttc
     3841 cttcatccat gacatactga cagaagtcct cactgactgg aatgagccac ctcattttca
     3901 cttcaatgaa gcactcttcc gacctttcga gcgcattatg cagctggaat tgtgtgatga
     3961 ggacgtccaa gaccaggttg tcacatccat tggtgagctg gttgaagtgt gttccacgca
     4021 gatccagtcg ggatggagac ccttgttcag tgccctggaa acagtgcatg gcgggaacaa
     4081 gtcagagatg aaggagtacc tggttggtga ctactccatg ggaaaaggcc aagctccagt
     4141 gtttgatgta tttgaagctt ttctcaatac tgacaacatc caggtctttg ctaatgcagc
     4201 cactagctac atcatgtgcc ttatgaagtt tgtcaaagga ctgggggagg tggactgtaa
     4261 agagattgga gactgtgccc cagcacccgg agccccgtcc acagacctgt gcctcccggc
     4321 cctggattac ctcaggcgct gctctcagtt attggccaaa atctacaaaa tgcccttgaa
     4381 gccaatattc cttagtggga gacttgccgg cttgcctcga agacttcagg aacagtcagc
     4441 cagcagtgag gatggaattg aatcagtcct gtctgatttt gatgatgaca ccggtctgat
     4501 agaagtctgg ataatcctgc tggagcagct gacagcggct gtgtccaatt gtccacggca
     4561 gcaccaacca ccaactctgg atttactctt tgagctgttg agagatgtga cgaaaacacc
     4621 aggaccaggg tttggtatct atgcagtggt tcacctcctc cttcctgtga tgtccgtttg
     4681 gctccgccgg agccataaag accattccta ctgggatatg gcctctgcca atttcaagca
     4741 cgctattggt ctgtcctgtg agctggtggt ggagcacatt caaagctttc tacattcaga
     4801 tatcaggtac gagagcatga tcaataccat gctgaaggac ctctttgagt tgctggtcgc
     4861 ctgtgtggcc aagcccactg aaaccatctc cagagtgggc tgctcctgta ttagatacgt
     4921 ccttgtgaca gcgggccctg tgttcactga ggagatgtgg aggcttgcct gctgtgccct
     4981 gcaagatgcg ttctctgcca cactcaagcc agtgaaggac ctgctgggct gcttccacag
     5041 cggcacggag agcttcagcg gggaaggctg ccaggtgcga gtggcggccc cgtcctcctc
     5101 cccaagtgcc gaggccgagt actggcgcat ccgagccatg gcccagcagg tgtttatgct
     5161 ggacacccag tgctcaccaa agacaccaaa caactttgac cacgctcagt cctgccagct
     5221 cattattgag ctgcctcctg atgaaaaacc aaatggacac accaagaaaa gcgtgtcttt
     5281 cagggaaatt gtggtgagcc tgctgtctca tcaggtgtta ctccagaact tatatgacat
     5341 cttgttagaa gagtttgtca aaggcccctc tcctggagag gaaaagacga tacaagtgcc
     5401 agaagccaag ctggctggct tcctcagata catctctatg cagaacttgg cagtcatatt
     5461 cgacctgctg ctggactctt ataggactgc cagggagttt gacaccagcc ccgggctgaa
     5521 gtgcctgctg aagaaagtgt ctggcatcgg gggcgccgcc aacctctacc gccagtctgc
     5581 gatgagcttt aacatttatt tccacgccct ggtgtgtgct gttctcacca atcaagaaac
     5641 catcacggcc gagcaagtga agaaggtcct ttttgaggac gacgagagaa gcacggattc
     5701 ttcccagcag tgttcatctg aggatgaaga catctttgag gaaaccgccc aggtcagccc
     5761 cccgagaggc aaggagaaga gacagtggcg ggcacggatg cccttgctca gcgtccagcc
     5821 tgtcagcaac gcagattggg tgtggctggt caagaggctg cacaagctgt gcatggaact
     5881 gtgcaacaac tacatccaga tgcacttgga cctggagaac tgtatggagg agcctcccat
     5941 cttcaagggc gacccgttct tcatcctgcc ctccttccag tccgagtcat ccaccccatc
     6001 caccgggggc ttctctggga aagaaacccc ttccgaggat gacagaagcc agtcccggga
     6061 gcacatgggc gagtccctga gcctgaaggc cggtggtggg gacctgctgc tgccccccag
     6121 ccccaaagtg gagaagaagg atcccagccg gaagaaggag tggtgggaga atgcggggaa
     6181 caaaatctac accatggcag ccgacaagac catttcaaag ttgatgaccg aatacaaaaa
     6241 gaggaaacag cagcacaacc tgtccgcgtt ccccaaagag gtcaaagtgg agaagaaagg
     6301 agagccactg ggtcccaggg gccaggactc cccgctgctt cagcgtcccc agcacttgat
     6361 ggaccaaggg caaatgcggc attccttcag cgcaggcccc gagctgctgc gacaggacaa
     6421 gaggccccgc tcaggctcca ccgggagctc cctcagtgtc tcggtgagag acgcagaagc
     6481 acagatccag gcatggacca acatggtgct aacagttctc aatcagattc agattctccc
     6541 agaccagacc ttcacggccc tccagcccgc agtgttcccg tgcatcagtc agctgacctg
     6601 tcacgtgacc gacatcagag ttcgccaggc tgtgagggag tggctgggca gggtgggccg
     6661 tgtctatgac atcattgtgt agccgactcc tgttctactc tcccaccaaa taacagtagt
     6721 gagggttaga gtcctgccaa tacagctgtt gcattttccc caccactagc cccacttaaa
     6781 ctactactac tgtctcagag aacagtgttt cctaatgtaa aaagcctttc caaccactga
     6841 tcagcattgg ggccatacta aggtttgtat ctagatgaca caaacgatat tctgattttg
     6901 cacattatta tagaagaatc tataatcctt gatatgtttc taactcttga agtatatttc
     6961 ccagtgcttt tgcttacagt gttgtcccca aatgggtcat tttcaaggat tactcatttg
     7021 aaaacactat attgatccat ttgatccatc atttaaaaaa taaatacaat tcctaaggca
     7081 atatctgctg gtaagtcaag ctgataaaca ctcagacatc tagtaccagg gattattaat
     7141 tggaggaaga tttatggtta tgggtctggc tgggaagaag acaactataa atacatattc
     7201 ttgggtgtca taatcaagaa agaggtgact tctgttgtaa aataatccag aacacttcaa
     7261 aattattcct aaatcattaa gattttcagg tattcaccaa tttccccatg taaggtactg
     7321 tgttgtacct ttatttctgt atttctaaaa gaagaaagtt ctttcctagc agggtttgaa
     7381 gtctgtggct tatcagcctg tgacacagag tacccagtga aagtggctgg tacgtagatt
     7441 gtcaagagac ataagaccga ccagccaccc tggctgttct tgtggtgttt gtttccatcc
     7501 ccaaggcaaa caaggaaagg aaaggaaaga agaaaaggtg ccttagtcct ttgttgcact
     7561 tccatttcca tgccccacaa ttgtctgaac ataaggtata gcatttggtt tttaagaaaa
     7621 caaaacatta agacgcaact cattttatat caacacgctt ggaggaaagg gactcaggga
     7681 agggagcagg gagtgtgggg tggggatgga ttatgatgaa atcattttca atcttaaaat
     7741 ataatacaac aatcttgcaa aattatggtg tcagttacac aagctctagt ctcaaaatga
     7801 aagtaatgga gaaagacact gaaatttaga aaattttgtc gatttaaaat atttctccta
     7861 tctaccaagt aaagttaccc tatgtttgat gtctttgcat tcagaccaat atttcaggtg
     7921 gatatttcta agtattacta gaaaatacgt ttgaaagctt tatcttatta tttacagtat
     7981 ttttatattt cttacattat cctaatgatt gaaaactcct caatcaagct tacttacaca
     8041 cattctacag agttatttaa ggcatacatt ataatctccc agccccattc ataatgaata
     8101 agtcaccctt taaatataag acacaaattc tacagtattg aaataaggat ttaaaggggt
     8161 atttgtaaac tttgccctcc ttgagaaata tggaactacc ttagaggtta agaggaaggc
     8221 agtgttctga cttctttagg tgatctgaaa aaaacaccct tatcatccag tgtaccatct
     8281 agagatcacc acagaatcca tttttttccc agttccacaa aacactctgt ttgccttcag
     8341 tttttactca ctagacaata attcaagttt agaaacaggt aatcagctat ttgatcttaa
     8401 aaggcaatga attgttggga tatcagtgaa ctatgttgta tacttttgaa tttttacatt
     8461 ttataaatgg aattgaaagt tggataactg ctttttttaa attttccaac agaagtaaca
     8521 ccacagttgc tttgtttctt tttatagctt acctgaggtt cagttcttct ttgtgaacct
     8581 gtgagtactc cacagtttac tgggggaaaa ggcttcagta aagcagaggc tagaattaca
     8641 gtatttatac atagcaactt ttcataaagt agaaaaattc aaaggaagct gtctcaattt
     8701 gagaatacca gctgggcacg gtggctcacg cctgtaatcc cagcacttac tttgggaggc
     8761 caaggtgggc agataacctg cggtcaggag tttgagacca ggctggacaa catggtgaaa
     8821 cctcgtctct actaaaaata caaaaattag ccaggtgtgg taggatgcac ctgtaatccc
     8881 agctacttag gaggccgaga caggagaatc gctcgaaccc aggaggcgga cgttgcagtg
     8941 agccaagatt gcaccattgc actccagact gggtgacaag agtgaaactc catctaaaaa
     9001 aaaaaaaaaa aaaaagtgaa tactgtatcc caaagtatgt tagttgtttg tttggaaatc
     9061 agcattctcc ccgatgctct attatgggat ccaaaattct tgaacataag tttaccctgt
     9121 actgtgtcca aacactgttc tagttctagc ctgattatgg gtcccaagaa taaaaggatg
     9181 agtaggtgta cagagctctt gacctacaat tttttaagag tgttttggta ccttcccatt
     9241 gtcttctcta taactcagtc ctaacatact ctgcactcga gttaccagcc atccacactg
     9301 acatcagatt tcaaccagaa ccatcactga gtgacagcag tacttctcag aggtatttgc
     9361 agcttgatgc aaagtagtct ctaatgagta ggcattcagg tggttcttcc cagcaggtgg
     9421 agaagaaagg gaggagatga agaacactga gaggggagtg gcaccttccc aggctgccca
     9481 gctcagtctc ttgccctgtt cctgtgactc agctgcccac tcccccaact ttgtttccct
     9541 ccctcccagt ctctgaaagt gtcaggtgtt tctctcctca cagtctcttt tgcagcaaca
     9601 gtaagacaaa attcaaggca gccttttaaa gttacgaaca gttattagca tgtatttaca
     9661 gacctaagca gaatgagagt ttatacattg tttttagttg cctgtattta tagccaaaag
     9721 tatattacct taaagttgag atctttctct tcttttccta aattttggta aagtgtgctt
     9781 catgaaacaa acatctggaa aactccaagt ataagagacc ctggactgat gatggcccag
     9841 ccaagtatat ggagggacag agttctctct gtcattaatg aggacatcgg ttttcacaat
     9901 tgaacctcat gcactgtcca cagcatctca cctagctcct gtatctcctg atctgctttt
     9961 aaaaatagtt agttaggctg cctttttaca ccaccttctc tctctcccct tgtggtaatt
    10021 ttccagcctt ccccatagat ataaaactag aacaccttta tgatttgggg tctatgtaat
    10081 gactgaccga taagaaccca ggcagatgct aacatactta acagctcgca ttaaaatact
    10141 ttaaatcagg cgtgatggct cattcctgta atctcaagca ctttgggagg ctaaggtggg
    10201 tggatctctt gaggtcagga gttcgagacc aacctggcca acgtggtgaa accccgtctc
    10261 tactaaaaat acaaaattag ccgggcatgg tggcagctgc ctgtaatccc agctactcgg
    10321 gaagctgagg caggagaatt gcttgaacct gggaggtggg gattgcagtc agccaagatt
    10381 gttctgcagc atgggtgaca aagtgagact tcgtctcaag taaataaaac taaaattttt
    10441 aaatcaaaca tgacaaaaat gttaatataa ttcagaagta ccttgaaatt gaaacatatt
    10501 tgtgcaatga tcattaggct ttttgtcctt gttgttttaa aatgaggctt atacagagtg
    10561 agttgagagt caagtagcct tcgctgtgag acggtaatgc agttatataa tagataccct
    10621 tgactttgcc agattcatca caatactgct tatacaggaa agttttctca gaaaggaaaa
    10681 tccattagta tcagtcccat caagccaaac agaatgaaga cctttgatag taatagcaag
    10741 aggttacaaa tagcagggag gaggcgagta gtgaatgtca ctgtgattgc aaacccttac
    10801 ctgtattatc acacgtagtc ctcacaacaa ccttgtgaga caagtgttgt gttcctcatt
    10861 ttttcagagg ggaacacaga cccagagagg ttaagaaatt tgcccaagat aacaagtaaa
    10921 aggcaaagtt ggttgcaaaa gaggtgtttc tgaattcaag ggccatactc tctctctgac
    10981 aacatgctct aagtccatag agtaagcact ctagtatgaa aaaaagtttc aaggaacgag
    11041 gccatgaaaa tgagactatt tgacatctca gatctgtctg ggatgttatg gaggttttta
    11101 aaaataaagt tgaaaaaaga aaatgaatca tgtttataca taaaaaaatc acatgtaaca
    11161 catttcaagt gtttgaaaat aaaaccaaaa tctaaacttt agtcttcaag cagacattca
    11221 gtgttacttt agaaaactca ctgaattagg tggaaatgat ggaataatac tattcatggc
    11281 cagctattaa cacagaagaa catggcagtg tgtgtctgga acggcatgca caatttgtaa
    11341 acctttttca aatatcattt aatcaactca gaataaagtg ccctgtagcc aacagtgcct
    11401 ctttacttgc ttctctggga aatacatggt actaaattag tagcacaaag tttgggaata
    11461 tgcaaaataa tggataacca tttttcaaaa tgtacattct ctgaagagga agcagctggt
    11521 tggacaggat ttcttgaaga gccaggtgct aagggcatca ggtcgacatc catagtaacc
    11581 atgtgccata acatctacac atttccactt gttttacaga caaggtaaca ggcagaagga
    11641 aaatccagag tcttgcagta agcagatgac aaaacttcaa tatgcttggg caccacttag
    11701 gtgaccccag ggagatttag tgtggcctta ggaaagcaaa agagcacttt ttattggaaa
    11761 tatgagcttg tcactgggaa agatttgtaa aattgatcaa gaacttgatt tataattatg
    11821 cctcaaaaaa aaaagttctc atttagtagt ggagcaatct agaaaacata ccttttttgt
    11881 ttgtttggaa gatcctcttt ccctggctgt attgtagtgt ttgctatttg atgtggaaat
    11941 aactaataac ttaagatttt ggaacagaac accctttaga tttccaaaac acaattctta
    12001 tttcagggaa gacagaccaa aaatatctcc tgagatcatt ggtttcttta taaattgtgg
    12061 taccactcca tcattgaaga gaaaccacta ccacaccact agcaccatac agaacctttt
    12121 ctctgtatct ttgtacaata ctacaaaggg gtaccaggga ggagagagtg gctgaccact
    12181 ttagtgacaa aacagcactc cactgctggt gaatcccatc taattatggt ccttccaccc
    12241 ttttcaacca ccaacaactg ttcgtactgt taattcctat cctgaaggtt taaccagtgg
    12301 ttgtctagta tcttctgtct ttagaacagt ggttctcaaa ctttagtaca catcagcatc
    12361 acctggaggg ccttttttta aaataagaca cagattgctg ggctcatggt cagagttccc
    12421 agttaagtaa atcaggaaat ttgtatttct aacaagttta taggtgaggc caatactgct
    12481 gttttgggaa ctatgctttg agaaccactg ccttgaaaaa atttccaact tctaccttta
    12541 agatcagcct gacttatcaa acgctagaga aaaactgaat ctacccttgg gcagatgact
    12601 tgggattgga ttctatacag cagtcttgct caatcttccc agtttccagt tttattatac
    12661 caacaattgg tttttacaag ctagaagaca atgaatgtat aagttctatg gaacagtgag
    12721 ataaatctaa gcttcttgtc tttgtattta gaaacattga ttctatggat gatcatttgt
    12781 atcatgttga ccctttgact tgtactgaag gtgattttaa atttaagtat gtagtgtttg
    12841 aatttcttcc atccatgtcg ttttaatgag atgtttccat gtcagctcct ttacagcctt
    12901 ggctcctggc ttacagattt ttgaatagtt gtttgcttgc cagttgtttt acatctttca
    12961 ttggccacca aaatattagc catttgagat gagatgagac tacttgttgt accttcatct
    13021 ttcatttaat tttctggcgt aaattaacat tttaatttca tatatatctg taaagagtct
    13081 acccaaaggc ttcacggaaa tttgcaaaat gaactaattc ccttttaagc agcaggtgtg
    13141 cctgtttttg acttttcagt aaatatgttg tttgtgcaca tatctacatg gtggagacca
    13201 tattcattat ttcatcttcc aaataatggg aaaaatataa aagtgaatca gtgtgctttg
    13261 ggaattcagt gaaatcatgt taactcatat agagggggcc ttagtttatc tcttctttac
    13321 tgaattaatt agttttggaa attcttttac cattaaaaaa aattaaggac catacagaga
    13381 atgatttaag aaaaaacaag tcacttaaaa atcatcacct atttataaac tgtattaatt
    13441 acacataatg cttattgatt caatgaggtt tctctaaaga cttctgctta ataaatatgc
    13501 tgacttcatt taaattagtt tagactattg taggaatgga aggaaatgat tatatttact
    13561 agaattagtg agatcagaaa gcatatcaga atgttgatga tatcaaggag acaatctaca
    13621 gagtttttgc ctctgtggat ggaaataagg gtgttttttt ttggtttttt ttttacttta
    13681 gtttcccata atttttggaa attatgtgtg catttagttc ttttagtaac actgatttta
    13741 aaattaaatt tcaaaagtca atctctaaga gtaatttatt tttgttttac caaccagtgc
    13801 caaaaaggag aggagggaat ccaaaagcca atcttttgaa ccaatgtgta aaagattatg
    13861 ttttttctta aagttaggga ggctcgggcc ctgacactgc cagccccagt gagcatccct
    13921 ggctacctcg ggattatgtg caagctgctt tgtcctacat ttctttcatc tggttcttat
    13981 tgggagtgct tctctctaat aaaaattgat ttcccacaaa ataggcaaag ctgaacaaag
    14041 atgaatgctt ttgataagtt gggtttcact tcagttgaaa caatgtgata gaatatccag
    14101 gtgtggcatg atggggcagg aggaggtgcc tagagggaaa agttattttt gtttcttagt
    14161 gttgtgttgt ggggatggga cagataagaa taagatgttt attgccctaa tcatgctaag
    14221 agactattat tcaatatgct tttcccgctt ttctaagagg aataaactta gacaaattac
    14281 attataaaca gttcccctac tactatctcc cactctagat aaagccagtg ggtggtatgg
    14341 gtccttttat tccttatagt attatgccaa agaatcaact tattttcatt gaagattata
    14401 aataaatgaa gcttgttata gccataatga tttgagtcag tataccattt tacctataaa
    14461 atgcaaaatt catccttgca accccattca ccaggagcct tgaagcattt tgtttactcc
    14521 aaaggccttg tcaaggaagc ataatttttt gttttgcctt cttatttagt cagtttggtc
    14581 atatttactt aaaaaaacaa actgaaaatc acactccttt atatgttgat ataactgatt
    14641 ttatagaatc tgtctgttct ttgtttaaca ggtctctgta agcaagcttg caagtgtatt
    14701 ttgtgtacat tttatctgag gtggaaatga aaattctaaa gagaaaatat tttaaaagat
    14761 attgtattta tgttgcttgt gttgtagaat aaagattcaa atgcattaaa aatctggtac
    14821 atgaaacaat tgtgtttact gaataaatat atataaata
//
