LOCUS       NM_005633               8906 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens SOS Ras/Rac guanine nucleotide exchange factor 1
            (SOS1), transcript variant 1, mRNA.
ACCESSION   NM_005633
VERSION     NM_005633.4
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 8906)
  AUTHORS   Yuan,Q., Wang,R., Li,X., Sun,F., Lin,J., Fu,Z. and Zhang,J.
  TITLE     DNMT1/miR-152-3p/SOS1 signaling axis promotes self-renewal and
            tumor growth of cancer stem-like cells derived from non-small cell
            lung cancer
  JOURNAL   Clin Epigenetics 16 (1), 55 (2024)
   PUBMED   38622665
  REMARK    GeneRIF: DNMT1/miR-152-3p/SOS1 signaling axis promotes self-renewal
            and tumor growth of cancer stem-like cells derived from non-small
            cell lung cancer.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 8906)
  AUTHORS   Daley,B.R., Vieira,H.M., Rao,C., Hughes,J.M., Beckley,Z.M.,
            Huisman,D.H., Chatterjee,D., Sealover,N.E., Cox,K., Askew,J.W.,
            Svoboda,R.A., Fisher,K.W., Lewis,R.E. and Kortum,R.L.
  TITLE     SOS1 and KSR1 modulate MEK inhibitor responsiveness to target
            resistant cell populations based on PI3K and KRAS mutation status
  JOURNAL   Proc Natl Acad Sci U S A 120 (47), e2313137120 (2023)
   PUBMED   37972068
  REMARK    GeneRIF: SOS1 and KSR1 modulate MEK inhibitor responsiveness to
            target resistant cell populations based on PI3K and KRAS mutation
            status.
REFERENCE   3  (bases 1 to 8906)
  AUTHORS   Alem,D., Yang,X., Beato,F., Sarcar,B., Tassielli,A.F., Dai,R.,
            Hogenson,T.L., Park,M.A., Jiang,K., Cai,J., Yuan,Y.,
            Fernandez-Zapico,M.E., Tan,A.C., Fleming,J.B. and Xie,H.
  TITLE     Translational relevance of SOS1 targeting for KRAS-mutant
            colorectal cancer
  JOURNAL   Mol Carcinog 62 (7), 1025-1037 (2023)
   PUBMED   37042566
  REMARK    GeneRIF: Translational relevance of SOS1 targeting for KRAS-mutant
            colorectal cancer.
REFERENCE   4  (bases 1 to 8906)
  AUTHORS   Li,Y., Yin,Y., He,Y., He,K. and Li,J.
  TITLE     SOS1 regulates HCC cell epithelial-mesenchymal transition via the
            PI3K/AKT/mTOR pathway
  JOURNAL   Biochem Biophys Res Commun 637, 161-169 (2022)
   PUBMED   36403479
  REMARK    GeneRIF: SOS1 regulates HCC cell epithelial-mesenchymal transition
            via the PI3K/AKT/mTOR pathway.
REFERENCE   5  (bases 1 to 8906)
  AUTHORS   Geng,X., Chen,L., Srinivasan,R.S., Kylat,R.J., Witte,M.H. and
            Erickson,R.J.
  TITLE     Lack of embryonic homozygous or adult heterozygous lymphatic
            phenotypes for a Sos1 mutation and lack of lymphatic embryonic
            phenotypes for a homozygous Cx47 mutation in mice
  JOURNAL   Lymphology 55 (3), 129-134 (2022)
   PUBMED   36446400
  REMARK    GeneRIF: Lack of embryonic homozygous or adult heterozygous
            lymphatic phenotypes for a Sos1 mutation and lack of lymphatic
            embryonic phenotypes for a homozygous Cx47 mutation in mice.
REFERENCE   6  (bases 1 to 8906)
  AUTHORS   Yang,S.S., Van Aelst,L. and Bar-Sagi,D.
  TITLE     Differential interactions of human Sos1 and Sos2 with Grb2
  JOURNAL   J Biol Chem 270 (31), 18212-18215 (1995)
   PUBMED   7629138
REFERENCE   7  (bases 1 to 8906)
  AUTHORS   Lemmon,M.A., Ladbury,J.E., Mandiyan,V., Zhou,M. and Schlessinger,J.
  TITLE     Independent binding of peptide ligands to the SH2 and SH3 domains
            of Grb2
  JOURNAL   J Biol Chem 269 (50), 31653-31658 (1994)
   PUBMED   7527391
REFERENCE   8  (bases 1 to 8906)
  AUTHORS   Lioubin,M.N., Myles,G.M., Carlberg,K., Bowtell,D. and
            Rohrschneider,L.R.
  TITLE     Shc, Grb2, Sos1, and a 150-kilodalton tyrosine-phosphorylated
            protein form complexes with Fms in hematopoietic cells
  JOURNAL   Mol Cell Biol 14 (9), 5682-5691 (1994)
   PUBMED   7520523
REFERENCE   9  (bases 1 to 8906)
  AUTHORS   Roberts,A.E.
  TITLE     Noonan Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301303
REFERENCE   10 (bases 1 to 8906)
  AUTHORS   Duronio,V., Welham,M.J., Abraham,S., Dryden,P. and Schrader,J.W.
  TITLE     p21ras activation via hemopoietin receptors and c-kit requires
            tyrosine kinase activity but not tyrosine phosphorylation of p21ras
            GTPase-activating protein
  JOURNAL   Proc Natl Acad Sci U S A 89 (5), 1587-1591 (1992)
   PUBMED   1371879
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC092672.3 and AC019171.4.
            
            On May 6, 2020 this sequence version replaced NM_005633.3.
            
            Summary: This gene encodes a protein that is a guanine nucleotide
            exchange factor for RAS proteins, membrane proteins that bind
            guanine nucleotides and participate in signal transduction
            pathways. GTP binding activates and GTP hydrolysis inactivates RAS
            proteins. The product of this gene may regulate RAS proteins by
            facilitating the exchange of GTP for GDP. Mutations in this gene
            are associated with gingival fibromatosis 1 and Noonan syndrome
            type 4. [provided by RefSeq, Jul 2008].
            
            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 :: L13857.1, SRR14038194.2492983.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000402219.8/ ENSP00000384675.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-716               AC092672.3         15269-15984         c
            717-842             AC019171.4         141006-141131       c
            843-974             AC019171.4         132051-132182       c
            975-1139            AC019171.4         130080-130244       c
            1140-1349           AC019171.4         127992-128201       c
            1350-1493           AC019171.4         124522-124665       c
            1494-1604           AC019171.4         108768-108878       c
            1605-1703           AC019171.4         108590-108688       c
            1704-1831           AC019171.4         97388-97515         c
            1832-2487           AC019171.4         95948-96603         c
            2488-2569           AC019171.4         88143-88224         c
            2570-2692           AC019171.4         87245-87367         c
            2693-2796           AC019171.4         86838-86941         c
            2797-3019           AC019171.4         85504-85726         c
            3020-3139           AC019171.4         83962-84081         c
            3140-3302           AC019171.4         80409-80571         c
            3303-3420           AC019171.4         79790-79907         c
            3421-3593           AC019171.4         70631-70803         c
            3594-3710           AC019171.4         70300-70416         c
            3711-3975           AC019171.4         68501-68765         c
            3976-4020           AC019171.4         62648-62692         c
            4021-4139           AC019171.4         60851-60969         c
            4140-8906           AC019171.4         54927-59693         c
FEATURES             Location/Qualifiers
     source          1..8906
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p22.1"
     gene            1..8906
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /note="SOS Ras/Rac guanine nucleotide exchange factor 1"
                     /db_xref="GeneID:6654"
                     /db_xref="HGNC:HGNC:11187"
                     /db_xref="MIM:182530"
     exon            1..716
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     CDS             630..4631
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /note="isoform 1 is encoded by transcript variant 1;
                     gingival fibromatosis, hereditary, 1; guanine nucleotide
                     exchange factor; son of sevenless homolog 1"
                     /codon_start=1
                     /product="son of sevenless homolog 1 isoform 1"
                     /protein_id="NP_005624.2"
                     /db_xref="CCDS:CCDS1802.1"
                     /db_xref="GeneID:6654"
                     /db_xref="HGNC:HGNC:11187"
                     /db_xref="MIM:182530"
                     /translation="MQAQQLPYEFFSEENAPKWRGLLVPALKKVQGQVHPTLESNDDA
                     LQYVEELILQLLNMLCQAQPRSASDVEERVQKSFPHPIDKWAIADAQSAIEKRKRRNP
                     LSLPVEKIHPLLKEVLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQ
                     DIKVAMCADKVLMDMFHQDVEDINILSLTDEEPSTSGEQTYYDLVKAFMAEIRQYIRE
                     LNLIIKVFREPFVSNSKLFSANDVENIFSRIVDIHELSVKLLGHIEDTVEMTDEGSPH
                     PLVGSCFEDLAEELAFDPYESYARDILRPGFHDRFLSQLSKPGAALYLQSIGEGFKEA
                     VQYVLPRLLLAPVYHCLHYFELLKQLEEKSEDQEDKECLKQAITALLNVQSGMEKICS
                     KSLAKRRLSESACRFYSQQMKGKQLAIKKMNEIQKNIDGWEGKDIGQCCNEFIMEGTL
                     TRVGAKHERHIFLFDGLMICCKSNHGQPRLPGASNAEYRLKEKFFMRKVQINDKDDTN
                     EYKHAFEIILKDENSVIFSAKSAEEKNNWMAALISLQYRSTLERMLDVTMLQEEKEEQ
                     MRLPSADVYRFAEPDSEENIIFEENMQPKAGIPIIKAGTVIKLIERLTYHMYADPNFV
                     RTFLTTYRSFCKPQELLSLIIERFEIPEPEPTEADRIAIENGDQPLSAELKRFRKEYI
                     QPVQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEFIGTVRGKAMKKWVESITKIIQRK
                     KIARDNGPGHNITFQSSPPTVEWHISRPGHIETFDLLTLHPIEIARQLTLLESDLYRA
                     VQPSELVGSVWTKEDKEINSPNLLKMIRHTTNLTLWFEKCIVETENLEERVAVVSRII
                     EILQVFQELNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKILEEAHELSEDHYKK
                     YLAKLRSINPPCVPFFGIYLTNILKTEEGNPEVLKRHGKELINFSKRRKVAEITGEIQ
                     QYQNQPYCLRVESDIKRFFENLNPMGNSMEKEFTDYLFNKSLEIEPRNPKPLPRFPKK
                     YSYPLKSPGVRPSNPRPGTMRHPTPLQQEPRKISYSRIPESETESTASAPNSPRTPLT
                     PPPASGASSTTDVCSVFDSDHSSPFHSSNDTVFIQVTLPHGPRSASVSSISLTKGTDE
                     VPVPPPVPPRRRPESAPAESSPSKIMSKHLDSPPAIPPRQPTSKAYSPRYSISDRTSI
                     SDPPESPPLLPPREPVRTPDVFSSSPLHLQPPPLGKKSDHGNAFFPNSPSPFTPPPPQ
                     TPSPHGTRRHLPSPPLTQEVDLHSIAGPPVPPRQSTSQHIPKLPPKTYKREHTHPSMH
                     RDGPPLLENAHSS"
     exon            717..842
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            843..974
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            975..1139
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1140..1349
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1350..1493
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1494..1604
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1605..1703
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1704..1831
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1832..2487
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            2488..2569
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            2570..2692
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            2693..2796
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            2797..3019
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            3020..3139
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            3140..3302
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            3303..3420
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            3421..3593
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            3594..3710
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            3711..3975
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            3976..4020
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            4021..4139
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     exon            4140..8906
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5739..5744
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /note="hexamer: ATTAAA"
     polyA_site      5761
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /note="major polyA site"
     regulatory      8876..8881
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /note="hexamer: AATAAA"
     regulatory      8880..8885
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /note="hexamer: AAGAAA"
     polyA_site      8903
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
                     /note="major polyA site"
     polyA_site      8906
                     /gene="SOS1"
                     /gene_synonym="GF1; GGF1; GINGF; HGF; NS4; SOS-1"
ORIGIN      
        1 agtagcgagc aggttcagtt cgctagtagg aagctccagc gctacaccgg cggcggcggt
       61 ggcggcggcg gccgcggcgg cacctcaggg cagccagatt ccccaacaac gacctccggt
      121 ccttcccctt ccccgcgaga cctccgcccc agctccgccc cgcccggggc tcttgcgttt
      181 cggagtccca actacgcgga gcgggcgccg cggccggagc gtccctccac acgtcctccc
      241 ccagccgcca gctccgccgc ggggccagac cgggcccggg agtgcagccc cggcgggcgg
      301 gcggcggccg cggcagaggg cagcccgggg cggcgccggc gggccgggga ggggcggggg
      361 gcctggcccc ggggcggtgg tgcgggatgc cgccgcctcc gggccgcgtc cgttctccac
      421 ggctggtacc tgtgtcgggt gggtggccag gcgcgggcct cgccccccag ccccctcgcc
      481 agggctagcc cggctgcgcg gcgcccggag ggggccgggc cgtccggtgg ggccgcggcc
      541 ctgttccgcg ctgcgagctc gccctctcgc ggctccctgg cccggccgcc gccgcccctc
      601 tccccgccca gaggcgcccc gggggcacca tgcaggcgca gcagctgccc tacgagtttt
      661 tcagcgaaga gaacgcgccc aagtggcggg gactactggt gcctgcgctg aaaaaggtcc
      721 aggggcaagt tcatcctact ctcgagtcta atgatgatgc tcttcagtat gttgaagaat
      781 taattttgca attattaaat atgctatgcc aagctcagcc ccgaagtgct tcagatgtag
      841 aggaacgtgt tcaaaaaagt ttccctcatc caattgataa atgggcaata gctgatgccc
      901 aatcagctat tgaaaagagg aagcgaagaa accctttatc tctcccagta gaaaaaattc
      961 atcctttatt aaaggaggtc ctaggttata aaattgacca ccaggtttct gtttacatag
     1021 tagcagtctt agaatacatt tctgcagaca ttttaaagct ggttgggaat tatgtaagaa
     1081 atatacggca ttatgaaatt acaaaacaag atattaaagt ggcaatgtgt gctgacaagg
     1141 tattgatgga tatgtttcat caagatgtag aagatattaa tatattatct ttaactgacg
     1201 aagagccttc cacctcagga gaacaaactt actatgattt ggtaaaagca tttatggcag
     1261 aaattcgaca atatataagg gaactaaatc taattataaa agtttttaga gagccctttg
     1321 tctccaattc aaaattgttt tcagctaatg atgtagaaaa tatatttagt cgcatagtag
     1381 atatacatga acttagtgta aagttactgg gccatataga agatacagta gaaatgacag
     1441 atgaaggcag tccccatcca ctagtaggaa gctgctttga agacttagca gaggaactgg
     1501 catttgatcc atatgaatcg tatgctcgag atattttgcg acctggtttt catgatcgtt
     1561 tccttagtca gttatcaaag cctggggcag cactttattt gcagtcaata ggcgaaggtt
     1621 tcaaagaagc tgttcaatat gttttaccca ggctgcttct ggcccctgtt taccactgtc
     1681 tccattactt tgaacttttg aagcagttag aagaaaaaag tgaagatcaa gaagacaagg
     1741 aatgtttaaa acaagcaata acagctttgc ttaatgttca gagtggtatg gaaaaaatat
     1801 gttctaaaag tcttgcaaaa cgaagactga gtgaatctgc atgtcggttt tatagtcagc
     1861 aaatgaaggg gaaacaacta gcaatcaaga agatgaacga gattcagaag aatattgatg
     1921 gttgggaggg aaaagacatt ggacagtgtt gtaatgaatt tataatggaa ggaactctta
     1981 cacgtgtagg agccaaacat gagagacaca tatttctctt tgatggctta atgatttgct
     2041 gtaaatcaaa tcatgggcag ccaagacttc ctggtgctag caatgcagaa tatcgtctta
     2101 aagaaaagtt ttttatgcga aaggtacaaa ttaatgataa agatgacacc aatgaataca
     2161 agcatgcttt tgaaataatt ttaaaagatg aaaatagtgt tatattttct gccaagtcag
     2221 ctgaagagaa aaacaattgg atggcagcat tgatatcttt acagtaccgg agtacactgg
     2281 aaaggatgct tgatgtaaca atgctacagg aagagaaaga ggagcagatg aggctgccta
     2341 gtgctgatgt ttatagattt gcagagcctg actctgaaga gaatattata tttgaagaga
     2401 acatgcagcc caaggctgga attccaatta tcaaagcagg aactgttatt aaacttatag
     2461 agaggcttac gtaccatatg tacgcagatc ccaattttgt tcggacattt cttacaacat
     2521 acagatcctt ttgcaaacct caagaactac tgagtcttat aatagaaagg tttgaaattc
     2581 cagagcctga gccaacagaa gctgatcgca tagctataga gaatggagat caacccttga
     2641 gtgcagaact gaaaagattt agaaaagaat atatacagcc tgtgcaactg cgagtattaa
     2701 atgtatgtcg gcactgggta gagcaccact tctatgattt tgaaagagat gcatatcttt
     2761 tgcaacgaat ggaagaattt attggaacag taagaggtaa agcaatgaaa aaatgggttg
     2821 aatccatcac taaaataatc caaaggaaaa aaattgcaag agacaatgga ccaggtcata
     2881 atattacatt tcagagttca cctcccacag ttgagtggca tataagcaga cctgggcaca
     2941 tagagacttt tgacctgctc accttacacc caatagaaat tgctcgacaa ctcactttac
     3001 ttgaatcaga tctataccga gctgtacagc catcagaatt agttggaagt gtgtggacaa
     3061 aagaagacaa agaaattaac tctcctaatc ttctgaaaat gattcgacat accaccaacc
     3121 tcactctgtg gtttgagaaa tgtattgtag aaactgaaaa tttagaagaa agagtagctg
     3181 tggtgagtcg aattattgag attctacaag tctttcaaga gttgaacaac tttaatggtg
     3241 tccttgaggt tgtcagtgct atgaattcat cacctgttta cagactagac cacacatttg
     3301 agcaaatacc aagtcgccag aagaaaattt tagaagaagc tcatgaattg agtgaagatc
     3361 actataagaa atatttggca aaactcaggt ctattaatcc accatgtgtg cctttctttg
     3421 gaatttatct cactaatatc ttgaaaacag aagaaggcaa ccctgaggtc ctaaaaagac
     3481 atggaaaaga gcttataaac tttagcaaaa ggaggaaagt agcagaaata acaggagaga
     3541 tccagcagta ccaaaatcag ccttactgtt tacgagtaga atcagatatc aaaaggttct
     3601 ttgaaaactt gaatccgatg ggaaatagca tggagaagga atttacagat tatcttttca
     3661 acaaatccct agaaatagaa ccacgaaacc ctaagcctct cccaagattt ccaaaaaaat
     3721 atagctatcc cctaaaatct cctggtgttc gtccatcaaa cccaagacca ggtaccatga
     3781 ggcatcccac acctctgcag caggagccaa ggaaaattag ttatagtagg atccctgaaa
     3841 gtgaaacaga aagtacagca tctgcaccaa attctccaag aacaccgtta acacctccgc
     3901 ctgcttctgg tgcttccagt accacagatg tttgcagtgt atttgattcc gatcattcga
     3961 gcccttttca ctcaagcaat gataccgtct ttatccaagt tactctgccc catggcccaa
     4021 gatctgcttc tgtatcatct ataagtttaa ccaaaggcac tgatgaagtg cctgtccctc
     4081 ctcctgttcc tccacgaaga cgaccagaat ctgccccagc agaatcttca ccatctaaga
     4141 ttatgtctaa gcatttggac agtcccccag ccattcctcc taggcaaccc acatcaaaag
     4201 cctattcacc acgatattca atatcagacc ggacctctat ctcagaccct cctgaaagcc
     4261 ctcccttatt accaccacga gaacctgtga ggacacctga tgttttctca agctcaccac
     4321 tacatctcca acctccccct ttgggcaaaa aaagtgacca tggcaatgcc ttcttcccaa
     4381 acagcccttc cccctttaca ccacctcctc ctcaaacacc ttctcctcac ggcacaagaa
     4441 ggcatctgcc atcaccacca ttgacacaag aagtggacct tcattccatt gctgggccgc
     4501 ctgttcctcc acgacaaagc acttctcaac atatccctaa actccctcca aaaacttaca
     4561 aaagggagca cacacaccca tccatgcaca gagatggacc accactgttg gagaatgccc
     4621 attcttcctg agttcctctg tactgggatg tatattttcc tagccccaaa tccattgctg
     4681 gcaatggatg cactgaatgt gccagcactg aggagttaaa atgagaactc caaacactaa
     4741 cgactcttct tcaagatgca gtataagaca atgaatttta acctagatgt aattatacaa
     4801 tggaaatggt attccagttt agaatatgga aagaccgacc tagaggaatt ggacaactga
     4861 ttgcacctga aaatcataaa gggacttttt ctggccaata ggcaggagtc ctctttttgt
     4921 gaagtgatct tttgtgaagt gatcattaaa gggatggaaa acacagtcta gtgtccagca
     4981 ggcccacatg acagtttttg taattcaaat tatgcacttt taaaaaaaaa aacttaaaca
     5041 gggatcttaa tatcttcctt tgttttcctt tgctttactc ttctacttta gaatattttc
     5101 ttaaaaatca ctcaaaggac tgtgaggaaa ggctgtggta cctgaccttg ttgaaatcaa
     5161 ggcccggcac tgtactacag gcctgtttac agattattac ggtgaactga atgggtaccg
     5221 aggcttcacc aaagaggtac ttttttgttg ttgttgttgt tttaggaata attgtaccaa
     5281 ttttaagagc attcccccca cctgtcccca cacacccaaa caaaatgtgg tggtgttgcc
     5341 ttcaaaaaag agaagttttg tgtcattaac atgacagaag aactttttaa aaaaaaataa
     5401 ctgtcaacta ttctatttgc atttaggaga ctgttcatct atgctagatt gtcattttcc
     5461 ctccttctcc cacagaagtt tactggtagt ccatgtcatg gctcgtagct atccctctaa
     5521 ccataccatg gaaatgcagg cacccaatgt gaaaaggagc acttgctggg catcactgac
     5581 accgctcatg ttttacacat agttgagtaa tcagcatatc tagaattatc ttgcattgcc
     5641 taaatcatat gtatatagtg aatgttatat aatatacctg gcaggtctgt tttaatttaa
     5701 ttgaataaag atacaaatac tttgtttggc tggcatatat taaattatta tatgaagaaa
     5761 atggttgatt cttatttctt ttagttgaaa aacacacaaa aacactaaac ataaaagcac
     5821 gttttgtggt acgccttggt ttctagttct ggatatatgt attaatctta aagaatgatc
     5881 taaagtcaca gcttggcata taggaagata cttggttaga ataggatggg tatcttttaa
     5941 gcagaacttt gtaagtaagt tttaagttcc taagcaacaa gtatacagtt tgttaaggtt
     6001 tatattgaac attctacctt gcttgaggtt ttctgcttta tcaaaactat tcataataga
     6061 acatctacct gcatcattac tatcataata tggattattc ataaagcgta tgtactgttc
     6121 ttctgagtct aacaaatact gtgactgaaa tgcatgcacc ttgttgaaga gaaaacattt
     6181 tattaatctc cactataatg tctgtgaaat gtgcagtatt ccatccttag agagtttatc
     6241 tggttcatca gcatctgcat gtatcctctg aataatgaag caacatttca gcaattctgt
     6301 taaccacacc attagagaca tttttagaag tgctgcaaca tggtgggaac ctagtacttt
     6361 aataatttcc tatgatattt attagagcat aaaatgtaca tcacgatagt acagtatgta
     6421 gtcctttaag accagaaggt atgttaactg caccatcatt aagcagtcta tcctattttc
     6481 ttatttattt gttagaattg aatcctttct caatatctgt accattccta tgatggtagc
     6541 cattcttctc tttataaaat atttcctctt tgaaaagcgt cctaaaacat taatttcaaa
     6601 tcccctcttg gatgcaaagt gtccctaaga ccatccattc aacagtattt atgtgagcca
     6661 acttactaga gccgctacaa ctaatcatga tagacagtcc agaatctccc tggactttat
     6721 actgggccag cctcattgtc cctaagattt ctctttttat gtctcatgga ttacttctct
     6781 ttttaattgc cccaggcaca ttccaaatga gaacctggta aaagtcacat tggaccccct
     6841 tcagtatgtc ttcggctaat gtgttagcct tcaataaggt gataacccct tttcaaccta
     6901 tctagtctat aaagaggaaa aattcagatt tggagttcta atcctatttc tcccaaaggg
     6961 aactattctt ctaccccatg gttctaggag accacttcac tgtgcaacag ttttacatgc
     7021 attgtggatg gaggatattt ttattctgaa ctgttacatt taggtaaaaa tattttctgc
     7081 agtggtaact gattagaaaa atgccaattg gatgccctta ggtggaggtg agaaaatggc
     7141 atccttgcct tcttctcaat atgaaacatt aactagttga caaatttatc cttgtagtaa
     7201 tgaaaatcta tttaatcagg gaccagaaat ggctgaggag ataaatgcat cattacaaaa
     7261 ttctgctttt gaatcctgga cattacaagg gggtaaatgc agcatgactt tttgttaacc
     7321 acattccaaa atgtggaaca tttcttttag aaatgaaaat atttcaaggc tgatgtattt
     7381 taagactaca cattatcagg aaacatacat tgagagttcg cttaattaaa ggttgttggg
     7441 catcaaatta tgtttagtag gttactattc tctaacaact caaggatgct ttaatggatc
     7501 tgaatttgac aaagagcatg ccacactaat actacagtca acaacagccc agagaacaat
     7561 tactatgtca gctggaggct atattatgat tctaaattct taaaggtttt tttccctcca
     7621 taaatcaaaa attaccttat gtaaaccaaa aattagttgg tatttatggt catgatctta
     7681 attctcaagt ttagcttaat cttgtatttc attgtttgtc ttctaatatg acagcttaaa
     7741 ttcagatttt taagtgactc agcaaaatag gaggagtgtc ccaatttatt agtgttgtac
     7801 atattgaaga aaaccttttt gttccttcag atttagaaag aaacagttta accatttatt
     7861 tcttggtatt ctgctgctgt gaataggttt acttattctt ttaacatata ttgtgtgact
     7921 acgcaagtat aggtcctgtt gtattgcatt aatctttacc agtaactaaa catcacaagg
     7981 ttaatattgg tttggctgaa agaattatgc agtaaagtta tttataaggg aacatgatga
     8041 ctttattcaa tatttttctt ctttgaaaca tctcattact aacttttaag attatttcat
     8101 aatcccttat acatgagcca atgaaatatt ttgagctcta cttaagaagc atgaagtcta
     8161 tattataaat ctaaacaaca aaagcacttg taacttgttt agtaaattcc atgccttatt
     8221 ttccattttt gacaccgtaa agtgcatttt ctgtcgactg tgagcaaatt tcccttttgc
     8281 ctttaatgaa aatagtgcat taagtagcca attgctgcag aattataaag caaattagct
     8341 aacagtgggt cacattggac taccactcaa agaaacaaga tgcataacag atgatggaag
     8401 gtacatgtgg tgtggcttag ggagagcgca cctgtgccag atgcatgcca ctttcagtag
     8461 ctgccaaatg tgcctttaat taagaacatc tctaattttt ttcttcagat caagtcagca
     8521 tttggggtcg ggatttgggc agggaacttt ggggtgcaaa tatctggtga aaccaccaga
     8581 gaatttgttt gtcaaagtga catgtataat tttagttgag acgtgtttgt gtatatatgt
     8641 gtatttgcct ttgtttagta gcacggttat ttgctaaaat aattgtcaaa aaattgctct
     8701 gtcggtcggt ctttgatgta agaacaaagt gtggtctata catctaatat ggcctttgta
     8761 cctaaccatg ttcataggta atctttgtac tctgtgtgca gcagtatttg gtttgcattt
     8821 aaagtgaaaa taacggctgt tatttttctg gcattactaa gataaactga aaaataataa
     8881 agaaaaatgc cttacatagc ccacaa
//
