LOCUS       NM_001195215            8365 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens DENN domain containing 1B (DENND1B), transcript
            variant 3, mRNA.
ACCESSION   NM_001195215
VERSION     NM_001195215.2
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 8365)
  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   2  (bases 1 to 8365)
  AUTHORS   Duffy,D.L., Siminovitch,K.A., Zamel,R., Chapman,K.R., Martin,N.G.
            and Zamel,N.
  TITLE     Variation at DENND1B and Asthma on the Island of Tristan da Cunha
  JOURNAL   Twin Res Hum Genet 22 (5), 277-282 (2019)
   PUBMED   31608842
  REMARK    GeneRIF: Variation at DENND1B and Asthma on the Island of Tristan
            da Cunha.
REFERENCE   3  (bases 1 to 8365)
  AUTHORS   Fiuza,B.S.D., Silva,M.J., Alcantara-Neves,N.M., Barreto,M.L.,
            Costa,R.D.S. and Figueiredo,C.A.
  TITLE     Polymorphisms in DENND1B gene are associated with asthma and atopy
            phenotypes in Brazilian children
  JOURNAL   Mol Immunol 90, 33-41 (2017)
   PUBMED   28668455
  REMARK    GeneRIF: polymorphisms in the DENND1B are significantly associated
            with development of asthma and atopy and these polymorphisms can
            influence DENND1B expression and consequently, asthma.
REFERENCE   4  (bases 1 to 8365)
  AUTHORS   Yang,C.W., Hojer,C.D., Zhou,M., Wu,X., Wuster,A., Lee,W.P.,
            Yaspan,B.L. and Chan,A.C.
  TITLE     Regulation of T Cell Receptor Signaling by DENND1B in TH2 Cells and
            Allergic Disease
  JOURNAL   Cell 164 (1-2), 141-155 (2016)
   PUBMED   26774822
  REMARK    GeneRIF: Study reveals a previously unrecognized mechanism by which
            DENND1B regulates surface TCR dynamics to fine-tune TH2 cell
            signaling and effector functions. Dennd1b-/- TH2 cells exhibit
            delayed TCR downmodulation following TCR activation that is
            associated with enhanced TCR signaling and greater transcriptional
            activation and secretion of TH2-associated cytokines.
REFERENCE   5  (bases 1 to 8365)
  AUTHORS   Kulasekaran,G., Nossova,N., Marat,A.L., Lund,I., Cremer,C.,
            Ioannou,M.S. and McPherson,P.S.
  TITLE     Phosphorylation-dependent Regulation of Connecdenn/DENND1 Guanine
            Nucleotide Exchange Factors
  JOURNAL   J Biol Chem 290 (29), 17999-18008 (2015)
   PUBMED   26055712
  REMARK    GeneRIF: The guanine nucleotide exchange factor activity of
            connecdenn 1 and 2 are autoinhibited, and this is regulated by Akt
            activation downstream of insulin stimulation.
REFERENCE   6  (bases 1 to 8365)
  AUTHORS   Mells,G.F., Floyd,J.A., Morley,K.I., Cordell,H.J., Franklin,C.S.,
            Shin,S.Y., Heneghan,M.A., Neuberger,J.M., Donaldson,P.T., Day,D.B.,
            Ducker,S.J., Muriithi,A.W., Wheater,E.F., Hammond,C.J.,
            Dawwas,M.F., Jones,D.E., Peltonen,L., Alexander,G.J., Sandford,R.N.
            and Anderson,C.A.
  CONSRTM   UK PBC Consortium; Wellcome Trust Case Control Consortium 3
  TITLE     Genome-wide association study identifies 12 new susceptibility loci
            for primary biliary cirrhosis
  JOURNAL   Nat Genet 43 (4), 329-332 (2011)
   PUBMED   21399635
  REMARK    Erratum:[Nat Genet. 2011 Nov;43(11):1164. Richardson,Paul [added];
            Nasr, Ikram [added]; Aspinall,Richard [added]]
            Publication Status: Online-Only
REFERENCE   7  (bases 1 to 8365)
  AUTHORS   Franke,A., McGovern,D.P., Barrett,J.C., Wang,K.,
            Radford-Smith,G.L., Ahmad,T., Lees,C.W., Balschun,T., Lee,J.,
            Roberts,R., Anderson,C.A., Bis,J.C., Bumpstead,S., Ellinghaus,D.,
            Festen,E.M., Georges,M., Green,T., Haritunians,T., Jostins,L.,
            Latiano,A., Mathew,C.G., Montgomery,G.W., Prescott,N.J.,
            Raychaudhuri,S., Rotter,J.I., Schumm,P., Sharma,Y., Simms,L.A.,
            Taylor,K.D., Whiteman,D., Wijmenga,C., Baldassano,R.N., Barclay,M.,
            Bayless,T.M., Brand,S., Buning,C., Cohen,A., Colombel,J.F.,
            Cottone,M., Stronati,L., Denson,T., De Vos,M., D'Inca,R.,
            Dubinsky,M., Edwards,C., Florin,T., Franchimont,D., Gearry,R.,
            Glas,J., Van Gossum,A., Guthery,S.L., Halfvarson,J.,
            Verspaget,H.W., Hugot,J.P., Karban,A., Laukens,D., Lawrance,I.,
            Lemann,M., Levine,A., Libioulle,C., Louis,E., Mowat,C., Newman,W.,
            Panes,J., Phillips,A., Proctor,D.D., Regueiro,M., Russell,R.,
            Rutgeerts,P., Sanderson,J., Sans,M., Seibold,F., Steinhart,A.H.,
            Stokkers,P.C., Torkvist,L., Kullak-Ublick,G., Wilson,D.,
            Walters,T., Targan,S.R., Brant,S.R., Rioux,J.D., D'Amato,M.,
            Weersma,R.K., Kugathasan,S., Griffiths,A.M., Mansfield,J.C.,
            Vermeire,S., Duerr,R.H., Silverberg,M.S., Satsangi,J.,
            Schreiber,S., Cho,J.H., Annese,V., Hakonarson,H., Daly,M.J. and
            Parkes,M.
  TITLE     Genome-wide meta-analysis increases to 71 the number of confirmed
            Crohn's disease susceptibility loci
  JOURNAL   Nat Genet 42 (12), 1118-1125 (2010)
   PUBMED   21102463
REFERENCE   8  (bases 1 to 8365)
  AUTHORS   Yoshimura,S., Gerondopoulos,A., Linford,A., Rigden,D.J. and
            Barr,F.A.
  TITLE     Family-wide characterization of the DENN domain Rab GDP-GTP
            exchange factors
  JOURNAL   J Cell Biol 191 (2), 367-381 (2010)
   PUBMED   20937701
REFERENCE   9  (bases 1 to 8365)
  AUTHORS   Marat,A.L. and McPherson,P.S.
  TITLE     The connecdenn family, Rab35 guanine nucleotide exchange factors
            interfacing with the clathrin machinery
  JOURNAL   J Biol Chem 285 (14), 10627-10637 (2010)
   PUBMED   20154091
REFERENCE   10 (bases 1 to 8365)
  AUTHORS   Sleiman,P.M., Flory,J., Imielinski,M., Bradfield,J.P., Annaiah,K.,
            Willis-Owen,S.A., Wang,K., Rafaels,N.M., Michel,S., Bonnelykke,K.,
            Zhang,H., Kim,C.E., Frackelton,E.C., Glessner,J.T., Hou,C.,
            Otieno,F.G., Santa,E., Thomas,K., Smith,R.M., Glaberson,W.R.,
            Garris,M., Chiavacci,R.M., Beaty,T.H., Ruczinski,I., Orange,J.S.,
            Allen,J., Spergel,J.M., Grundmeier,R., Mathias,R.A., Christie,J.D.,
            von Mutius,E., Cookson,W.O., Kabesch,M., Moffatt,M.F.,
            Grunstein,M.M., Barnes,K.C., Devoto,M., Magnusson,M., Li,H.,
            Grant,S.F., Bisgaard,H. and Hakonarson,H.
  TITLE     Variants of DENND1B associated with asthma in children
  JOURNAL   N Engl J Med 362 (1), 36-44 (2010)
   PUBMED   20032318
  REMARK    GeneRIF: We have identified a locus containing DENND1B on
            chromosome 1q31.3 that is associated with susceptibility to asthma.
            Erratum:[N Engl J Med. 2010 Sep 2;363(10):994]
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            DA495773.1, BK006960.1, BP220095.1, BC074735.2, AL139136.17,
            AK093982.1 and AI692985.1.
            
            On Nov 22, 2018 this sequence version replaced NM_001195215.1.
            
            Summary: Clathrin (see MIM 118955)-mediated endocytosis is a major
            mechanism for internalization of proteins and lipids. Members of
            the connecdenn family, such as DENND1B, function as guanine
            nucleotide exchange factors (GEFs) for the early endosomal small
            GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor
            protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35
            activation with the clathrin machinery (Marat and McPherson, 2010
            [PubMed 20154091]).[supplied by OMIM, Nov 2010].
            
            Transcript Variant: This variant (3) represents the longest
            transcript and encodes the longest isoform (3).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BK006960.1, DRR138523.308892.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000620048.6/ ENSP00000479816.1
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-325               DA495773.1         14-338
            326-1566            BK006960.1         1-1241
            1567-1567           BP220095.1         117-117
            1568-2315           BK006960.1         1243-1990
            2316-2316           BC074735.2         715-715
            2317-2653           BK006960.1         1992-2328
            2654-8274           AL139136.17        32579-38199         c
            8275-8357           AK093982.1         2182-2264
            8358-8365           AI692985.1         20-27               c
FEATURES             Location/Qualifiers
     source          1..8365
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q31.3"
     gene            1..8365
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /note="DENN domain containing 1B"
                     /db_xref="GeneID:163486"
                     /db_xref="HGNC:HGNC:28404"
                     /db_xref="MIM:613292"
     exon            1..342
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     CDS             326..2653
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /note="isoform 3 is encoded by transcript variant 3;
                     family with sequence similarity 31, member B; DENN
                     domain-containing protein 1B; connecdenn 2; DENN/MADD
                     domain containing 1B"
                     /codon_start=1
                     /product="DENN domain-containing protein 1B isoform 3"
                     /protein_id="NP_001182144.1"
                     /db_xref="CCDS:CCDS72997.1"
                     /db_xref="GeneID:163486"
                     /db_xref="HGNC:HGNC:28404"
                     /db_xref="MIM:613292"
                     /translation="MDCRTKANPDRTFDLVLKVKCHASENEDPVVLWKFPEDFGDQEI
                     LQSVPKFCFPFDVERVSQNQVGQHFTFVLTDIESKQRFGFCRLTSGGTICLCILSYLP
                     WFEVYYKLLNTLADYLAKELENDLNETLRSLYNHPVPKANTPVNLSVNQEIFIACEQV
                     LKDQPALVPHSYFIAPDVTGLPTIPESRNLTEYFVAVDVNNMLQLYASMLHERRIVII
                     SSKLSTLTACIHGSAALLYPMYWQHIYIPVLPPHLLDYCCAPMPYLIGIHSSLIERVK
                     NKSLEDVVMLNVDTNTLESPFSDLNNLPSDVVSALKNKLKKQSTATGDGVARAFLRAQ
                     AALFGSYRDALRYKPGEPITFCEESFVKHRSSVMKQFLETAINLQLFKQFIDGRLAKL
                     NAGRGFSDVFEEEITSGGFCGGNPRSYQQWVHTVKKGGALFNTAMTKATPAVRTAYKF
                     AKNHAKLGLKEVKSKLKHKENEEDYGTCSSSVQYTPVYKLHNEKGGNSEKRKLAQARL
                     KRPLKSLDGALYDDEDDDDIERASKLSSEDGEEASAYLYESDDSVETRVKTPYSGEMD
                     LLGEILDTLSTHSSDQGKLAAAKSLDFFRSMDDIDYKPTNKSNAPSENNLAFLCGGSG
                     DQAEWNLGQDDSALHGKHLPPSPRKRVSSSGLTDSLFILKEENSNKHLGADNVSDPTS
                     GLDFQLTSPEVSQTDKGKTEKRETLSQISDDLLIPGLGRHSSTFVPWEKEGKEAKETS
                     EDIGLLHEVVSLCHMTSDFQQSLNISDKNTNGNQT"
     exon            343..407
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            408..451
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            452..501
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            502..621
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            622..691
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            692..772
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            773..832
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            833..886
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            887..997
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            998..1098
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1099..1144
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1145..1246
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1247..1372
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1373..1474
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1475..1565
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1566..1606
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1607..1675
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1676..1732
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1733..1840
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1841..1923
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            1924..2140
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     exon            2141..8365
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /inference="alignment:Splign:2.1.0"
     regulatory      8344..8349
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /note="hexamer: AATAAA"
     polyA_site      8365
                     /gene="DENND1B"
                     /gene_synonym="C1ORF18; C1orf218; FAM31B"
                     /note="major polyA site"
ORIGIN      
        1 gcaagaaggt gcaggagccg cagcgggcgg ccccggtcgc aggaactgag aggcctcagc
       61 tttggtggcg gctaccggcg gagacggggg cggcggccac gccaccgctg ctgtcacaga
      121 aaggctctgg tgggtggggt gggaggcggg gaagtgccgg gggcgcagcc gacatgggcc
      181 cgccgccacg gctgctgtga gcagcctctt tccctgtgtg gccgccggcg tgggcgggga
      241 cggcgcgacc ctcgcgcggc cgggctgcgg gcttccaggc cagcgcgcgg gggccggacg
      301 gacagcccca caccgacatg taaccatgga ctgcaggacc aaggcaaatc cagacagaac
      361 ctttgacttg gtgttgaaag tgaaatgtca tgcctctgaa aatgaagatc ctgtggtatt
      421 gtggaaattc ccagaggact ttggagacca ggaaatacta cagagtgtgc caaagttctg
      481 ttttcccttt gacgttgaaa gggtgtctca gaatcaagtt ggacagcact ttacctttgt
      541 actgacagac attgaaagta aacagagatt tggattctgc agactgacgt caggaggcac
      601 aatttgttta tgcatcctta gttaccttcc ctggtttgaa gtgtattaca agcttctaaa
      661 tactcttgca gattacttgg ctaaggaact ggaaaatgat ttgaatgaaa ctctcagatc
      721 actgtataac cacccagtac caaaggcaaa tactcctgta aatttgagtg tgaaccaaga
      781 gatatttatt gcctgtgagc aagttctgaa agatcagcct gctctagtac cgcattccta
      841 cttcattgcc cctgatgtaa ctggactccc aacaataccc gagagtagaa atcttacaga
      901 atattttgtt gccgtggatg tgaacaacat gctgcagctg tatgccagta tgctgcatga
      961 aaggcgcatc gtgattatct cgagcaaatt aagcacttta actgcctgta tccatggatc
     1021 agctgctctt ctatacccaa tgtattggca acacatatac atcccagtgc ttcctccaca
     1081 cctgctggac tactgctgtg ccccaatgcc atacctgatt ggaatacact ccagcctcat
     1141 agagagagtg aaaaacaaat cattggaaga tgttgttatg ttaaatgttg atacaaacac
     1201 attagaatca ccatttagtg acttgaacaa cctaccaagt gatgtggtct cggccttgaa
     1261 aaataaactg aagaagcagt ctacagctac gggtgatgga gtagctaggg cctttcttag
     1321 agcacaggct gctttgtttg gatcctacag agatgcactg agatacaaac ctggtgagcc
     1381 catcactttc tgtgaggaga gttttgtaaa gcaccgctca agcgtgatga aacagttcct
     1441 ggaaactgcc attaacctcc agctttttaa gcagtttatc gatggtcgac tggcaaaact
     1501 aaatgcagga aggggtttct ctgatgtatt tgaagaagag atcacttcag gtggcttttg
     1561 tggagggaac ccgaggtcat atcaacaatg ggtgcataca gtcaagaaag gaggtgcact
     1621 gttcaacaca gcaatgacca aagcaacccc tgctgtacgg acagcatata aatttgcaaa
     1681 aaatcatgca aagctgggac taaaggaagt gaagagtaaa ctaaaacaca aggaaaatga
     1741 agaagattat gggacctgtt ctagttctgt acaatataca ccagtttaca aattacacaa
     1801 tgaaaaggga ggaaactcag aaaagcgtaa gcttgctcag gcacgcttaa aaaggcctct
     1861 taagagcctt gatggtgctc tatatgatga tgaagatgat gatgacattg aaagagcaag
     1921 caagttatct tctgaagatg gtgaagaagc ttctgcttat ctctatgaga gtgatgactc
     1981 tgttgaaaca agagtgaaga ctccttactc aggtgaaatg gacttactag gagagattct
     2041 tgatacattg agcacacaca gctcagatca ggggaagctg gcagctgcaa agagcttgga
     2101 tttctttaga tcaatggatg acattgatta caaacctacg aataaatcta atgctcctag
     2161 tgagaataac ctggctttcc tctgtggtgg ttctggtgac caagcagagt ggaatcttgg
     2221 gcaagacgat agtgccctcc atggcaaaca cctccctcca tctcctagga agcgggtttc
     2281 ctctagtggt ttgacagatt ctctgtttat cctgaaagag gaaaacagta acaagcacct
     2341 cggtgctgac aatgtgagtg accctacttc aggactggat ttccaactca cttcccctga
     2401 agtttcccag actgataaag gaaaaacaga aaagagggaa acactaagcc agatttcaga
     2461 tgatctgctt atacccggtc ttgggcggca ttcatcgact tttgttcctt gggagaaaga
     2521 agggaaagaa gccaaagaga cttcagaaga tattggactg ctccatgaag tagtgtcatt
     2581 atgtcatatg acatctgact tccaacaaag cttgaacatt tcagacaaaa acacaaatgg
     2641 aaaccaaact taaatcttgc atccaagctt ctatggagac attttgagat tcaatgcaat
     2701 ctgtataata aacagaatta tttgtaggaa tggcaactca tactatttaa attttttttt
     2761 gcatttgcaa catttttctc acttgttcat ttcgaggata tatgaaatgc attgattttt
     2821 aaatataaag cgaattctac tgtgctttta aatcaggtac tagtgtgtat gtatgtttaa
     2881 agtatgtatt gaccatgaga tttcccagtg tttggtgctt aatgccgttt attttattta
     2941 agctaagaat gcatatgtaa cccatgcaca taaccagtag ctactatact aatctggttg
     3001 agcatgaact gatcaagata tcaaaactta tcaaaactag cctgaagctg atgaaactgt
     3061 taacccacta attgccttaa tcttaaagct gttttttaag catacttaaa taatgtatga
     3121 aagtatgtat aaagtttgaa ggataagtta ttagtgttct gcagagcaat aatgcctttt
     3181 tctattcatc aaatcaaggt caaaattcat cttttcaaga ttaaaaagct ctcttaatgg
     3241 aaatatttaa tttgcttata taaagcacta tagccatgtt ttccaaaaag tataaaaata
     3301 tacacttacc tttcattcag tgaaatatag gaagtgctga attacaatgt gaagttaatg
     3361 acttctgttt acaaatgaga cactctaacg agttttcagt ctctctgtat gcctttgcta
     3421 tttaggggtc caccccaaga aagccaaata caacataaac cgtcctgaca aaaaaaaaaa
     3481 aaaaaatctt tttttaacta ataattctct atcaaaatgc ttcatatcat catctcaaat
     3541 ttacttttta aaataattga ctttgtattt tagaagtttt agatttacag aaaaattgca
     3601 aagatagtac agagagttcc catctacccc tgttactaac atcttacgtt actatggtac
     3661 atctgcccca attagtgaac caatattgat attccatact ttattcagat tttcttagtt
     3721 ttctcctaat atccattttc cacatcaaga tcctattcag aataccacac tatattgagt
     3781 tggaatgtct ccttaggctc ctcttgcctg tgacagtttc ttagactttc cttatttttg
     3841 atgacattga cagctttgaa gagtactgtc agataaattg tagcatgctc ctctcttgga
     3901 gtttgttggg tatttttttc atgattagac tgggattgtg ggttttgagg agatgatcac
     3961 agaagtaaag tgccattttc atcaggtcat atcaagggta cgtactgtca acatgatttg
     4021 tgaatgctga cagggacctt gataacctgg ctgaggtagc gtttgtcact ctaaagttct
     4081 tcctgccctt tccatgctgt catttttgga aggaagtcac tacatgcagg agtgaggagt
     4141 cataattccc cttctttagg gcagagaagt atctacataa ataactggga attctgtata
     4201 gaaaatttgt ttcttctttc tcaaattcac tgttgagctt tggaattcat ctgagaagga
     4261 atcatgtact aattacttca tgatagacta gattaccagg cacaatcagg gaaaaaagca
     4321 gtgatagtat ggttaaattg ttattagcat tttcagtata tccactttat acatccccaa
     4381 tcatgatttt ttttacattt ctttttagaa aagatgttca agaaatcatt aaagaacccc
     4441 aataagacta tattctaaat atttattgaa agaatataat ttcagctaaa atcctagaag
     4501 agggtttgaa ataatttaaa gaaaatgacc aagttttttt aaaacctacg tttcaaaatc
     4561 taaatggata tgtgttattt gggacactta ttcattatga ttatataaga agacaattct
     4621 tgtttccctt ataagtatgg actgtataca ttaaggaaaa caatgtttaa tccttatttt
     4681 ttaatacaga agtctcaagg ttcttgtcaa attttgcctt tataagctta ttacaaaatt
     4741 acaacttact ttactgaagt ttataatgga agaagtccat atagcaaaag agctgtttta
     4801 aatcagaagg aaaaaaggtt actctggttg ttaatctgct tggcaaatat tccttcataa
     4861 tttgtgaaaa gaatgcaaat cagcatttta atatgaattt tgaaatgagg tatggttttt
     4921 tgtttgtttt tttcagaact cagtctgaaa aacaactgtg agtgtagcat gggtcaaatt
     4981 tggtttttag tccatttgct ttatcaacat cacggcttca gaaatccaaa ttttgttcta
     5041 cttttcagcc acctttcaag gtgtttggtt ataatactgt gttgctttga ggatatttag
     5101 ccactcataa ataattgtct caaggtattt aaaagtgatt tgtgccttat tttaatgcaa
     5161 aattagcagt tttattctat tttaaaaaca aaggcagaaa aacaattctg catgttattc
     5221 tttaaaaaca tccagaataa tactaccaag tatttgtatt tcaaaccagt aaaattttga
     5281 atattcaaag tctgctctta aacttagact tcctagtatt atggtggtta tagtgagaat
     5341 gaaattaaac tgggtgagtt ccgaaataaa ggaaagtgtt atattctaca gtgcccatat
     5401 tttctatggt aactaaatca aatatttgta agttcctctg ctttttgaaa ttatttttca
     5461 aagaagcaac acctgttata caacagaatt gtataaacta aaaagacttt tggccttggt
     5521 acatagtctt tatctggcct gcaatggagt catggttctt tctgaatccc actctcactt
     5581 ttttcttttt acccttagat attgcatccg tggtatttca ggggtataga gaaataatat
     5641 tggaatttag gagctatttt tttaagtgaa aatattacta agtggtatct tttgatgatt
     5701 acctacttta atgtgtctta gaaaagcacc aaaacatagc atgattattt tttcagttaa
     5761 ttaaaattag ttaataacat gttcatttaa aaactattca ttgacttttt gtaccagtca
     5821 tatgcagggt acagtaactg aggatatggg aaataaaata actgacatag tccctgctct
     5881 gaaggaacaa aggaaaagga attgcaaatt tttattaaaa taataataat aataataata
     5941 ataataataa taataataat aatgtgtttt gcctggaagt tattagctga gattctaaca
     6001 cacaaaaagt tcaaaaaaaa agaacaaaaa ctggctgctt aatttaaagc atgctctaag
     6061 tatgaaccat agtatcattt ctaatttcat taactttctc aattattatg ctaagtatat
     6121 tatgctgcta agatacccac atttaagggg cagatttaga gactctttta gaaactgagt
     6181 gtctttatct tattatcaga taaccaggct gcacagggct ctctataatg gaatgatgct
     6241 ccttttcaat acttagagcc actgtactca gtttaggagt aactgaaggt gtggatgcat
     6301 gttaatggga atccaatttt tactattttt atatgaataa cagcgttctg tagaaacagt
     6361 ctctcccttc taaataaaaa ctatgtgact gctgttacta gtgctattct atgcgaatat
     6421 cctaataata ggattcagga attctaatga attgtttctt aattaaggtg aacaagtaga
     6481 ctcctgatca agaggagaac actgtgaatg tctcataatc aatagacctt cattctcttg
     6541 tagaaaatgt ggattttcag gaaaagactg attattttca tgaataaatt ttcttataca
     6601 aattccattt tgtttgacat aaaagaccct gaatcttaag atatttgtaa atcagaatat
     6661 ttaagaatgt aaaatgaatc cccaaatcta gtttcctcca aagcacttct taatgtagga
     6721 aatagttttt acaaacccta tgtcagtact aatgttcctg ggtcaaaccc agtaatattg
     6781 ttagtgtatg ttgttacacc ttatttaaga ggcagagtgg ttttgagcaa gtcagttaac
     6841 gtgatttgat gaagaaataa ggaattatat acatttagac agaagaatat tttattttga
     6901 aaataggatt tcgtgcaata atttttcttg cataacttag ttcatataaa tatgtacatc
     6961 tgtttttctg gcagatgcct taaggtcatg tttttcagta tttgagtaaa tctgtatgta
     7021 gcaatgttct cattgatttc agaaaaaaat atattcttta tattgttgcc aggagaaatg
     7081 tttttgttta tttaaaatta ttatggatat tgtgttgttg tatcataact aactgcctca
     7141 gcaacaataa atatgcaata agaaaatcct gtaccttaga ttagattgac aatactgtta
     7201 ctttaaaaga aatatatacg gtacaaattg ctgattctac atgtgtacat ttaacagata
     7261 ctcagttctg caccacctaa atcaaaatgg catttgtatg ctgatgatta catatgtgga
     7321 ttgtagtatc ctttgtgatg aatctttgat aagatttata aagggcattg ccaatacttt
     7381 ttgactgtgt aaattaattt tttgtatgat gtacagtttg tttaatctta gagcttctat
     7441 agatttctac tttattatac ttgaatgagg cagaaaagca ctgtggaaaa tctgtagctc
     7501 tggatgcaac atgcagacat accaaaaaaa taataataaa gcaaggtact gaagagcaat
     7561 gttaacagaa tgctttatat ccagaatgct atgttttttt caagccacat tttagttgaa
     7621 tgaagtaaag ttattcaatc ttttatttta aaatattgga aagtcacaaa tgattacttc
     7681 tttgatatga tgaacctata agtctattca tctctgttat ttcatttctc aaatgtgagc
     7741 cttgttgagg tccattatca aatctacact ttggttgatt atatgatgtt taggacaagg
     7801 cagaatttaa aacctgcatg tttagtgcat cacatgtcaa gtcaccatcc ttctgacagt
     7861 gtaacttcca taacgttatt ttgagagcca tttaataatc atatttgaaa aagtggattt
     7921 cttgagtctg ttgtagttta gtacttacag cagtgcctaa aacagcaact aatatgaact
     7981 gcctgagtcc tacaacataa atgcataaag cttttttatg taaaagccac aggaggggtt
     8041 caaaattgaa cttttccaaa gtttatttct cttgcgttag atgaaaaact atttaaaagg
     8101 actgaaaacc ctgagctttt tgctcgtctt ggtagcagat atctgtaaaa acctacccag
     8161 aattgtgatt ttacttcatt gttcttgcat ccttgaggct acagtataaa tcatctccaa
     8221 acttgactac tattgggaag atgtgtataa aagcatcgct ttgggaattt ttttaaaaat
     8281 atgcaaaaat aaatattgaa taaaatctac attaccataa aacacccaaa aatgcagttc
     8341 taaaataaaa ttggtcacaa ttaaa
//
