LOCUS       NM_015313              10326 bp    mRNA    linear   PRI 07-FEB-2025
DEFINITION  Homo sapiens Rho guanine nucleotide exchange factor 12 (ARHGEF12),
            transcript variant 1, mRNA.
ACCESSION   NM_015313 NM_018537
VERSION     NM_015313.3
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 10326)
  AUTHORS   Yang,Y., Wang,S., Cai,J., Liang,J., Zhang,Y., Xie,Y., Luo,F.,
            Tang,J., Gao,Y., Shen,S., Feng,H. and Li,Y.
  TITLE     Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN
            degradation, and reduces tumorigenicity
  JOURNAL   Cell Oncol (Dordr) 46 (1), 133-143 (2023)
   PUBMED   36520365
  REMARK    GeneRIF: Targeting ARHGEF12 promotes neuroblastoma differentiation,
            MYCN degradation, and reduces tumorigenicity.
            Erratum:[Cell Oncol (Dordr). 2023 Dec;46(6):1871-1872. doi:
            10.1007/s13402-023-00890-x.. PMID: 37843798]
REFERENCE   2  (bases 1 to 10326)
  AUTHORS   Khan,A., Ni,W., Baltazar,T., Lopez-Giraldez,F., Pober,J.S. and
            Pierce,R.W.
  TITLE     ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular
            endothelial cells to reduce tumor necrosis factor-induced leak
  JOURNAL   FASEB J 36 (4), e22254 (2022)
   PUBMED   35294066
  REMARK    GeneRIF: ArhGEF12 activates Rap1A and not RhoA in human dermal
            microvascular endothelial cells to reduce tumor necrosis
            factor-induced leak.
REFERENCE   3  (bases 1 to 10326)
  AUTHORS   Cho,N.H., Cheveralls,K.C., Brunner,A.D., Kim,K., Michaelis,A.C.,
            Raghavan,P., Kobayashi,H., Savy,L., Li,J.Y., Canaj,H., Kim,J.Y.S.,
            Stewart,E.M., Gnann,C., McCarthy,F., Cabrera,J.P., Brunetti,R.M.,
            Chhun,B.B., Dingle,G., Hein,M.Y., Huang,B., Mehta,S.B.,
            Weissman,J.S., Gomez-Sjoberg,R., Itzhak,D.N., Royer,L.A., Mann,M.
            and Leonetti,M.D.
  TITLE     OpenCell: Endogenous tagging for the cartography of human cellular
            organization
  JOURNAL   Science 375 (6585), eabi6983 (2022)
   PUBMED   35271311
REFERENCE   4  (bases 1 to 10326)
  AUTHORS   Swaney,D.L., Ramms,D.J., Wang,Z., Park,J., Goto,Y., Soucheray,M.,
            Bhola,N., Kim,K., Zheng,F., Zeng,Y., McGregor,M., Herrington,K.A.,
            O'Keefe,R., Jin,N., VanLandingham,N.K., Foussard,H., Von Dollen,J.,
            Bouhaddou,M., Jimenez-Morales,D., Obernier,K., Kreisberg,J.F.,
            Kim,M., Johnson,D.E., Jura,N., Grandis,J.R., Gutkind,J.S.,
            Ideker,T. and Krogan,N.J.
  TITLE     A protein network map of head and neck cancer reveals PIK3CA mutant
            drug sensitivity
  JOURNAL   Science 374 (6563), eabf2911 (2021)
   PUBMED   34591642
REFERENCE   5  (bases 1 to 10326)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   6  (bases 1 to 10326)
  AUTHORS   Harrington,A.W., Kim,J.Y. and Yoon,S.O.
  TITLE     Activation of Rac GTPase by p75 is necessary for c-jun N-terminal
            kinase-mediated apoptosis
  JOURNAL   J Neurosci 22 (1), 156-166 (2002)
   PUBMED   11756498
REFERENCE   7  (bases 1 to 10326)
  AUTHORS   Taya,S., Inagaki,N., Sengiku,H., Makino,H., Iwamatsu,A.,
            Urakawa,I., Nagao,K., Kataoka,S. and Kaibuchi,K.
  TITLE     Direct interaction of insulin-like growth factor-1 receptor with
            leukemia-associated RhoGEF
  JOURNAL   J Cell Biol 155 (5), 809-820 (2001)
   PUBMED   11724822
REFERENCE   8  (bases 1 to 10326)
  AUTHORS   Reuther,G.W., Lambert,Q.T., Booden,M.A., Wennerberg,K.,
            Becknell,B., Marcucci,G., Sondek,J., Caligiuri,M.A. and Der,C.J.
  TITLE     Leukemia-associated Rho guanine nucleotide exchange factor, a Dbl
            family protein found mutated in leukemia, causes transformation by
            activation of RhoA
  JOURNAL   J Biol Chem 276 (29), 27145-27151 (2001)
   PUBMED   11373293
REFERENCE   9  (bases 1 to 10326)
  AUTHORS   Fukuhara,S., Chikumi,H. and Gutkind,J.S.
  TITLE     Leukemia-associated Rho guanine nucleotide exchange factor (LARG)
            links heterotrimeric G proteins of the G(12) family to Rho
  JOURNAL   FEBS Lett 485 (2-3), 183-188 (2000)
   PUBMED   11094164
REFERENCE   10 (bases 1 to 10326)
  AUTHORS   Kourlas,P.J., Strout,M.P., Becknell,B., Veronese,M.L., Croce,C.M.,
            Theil,K.S., Krahe,R., Ruutu,T., Knuutila,S., Bloomfield,C.D. and
            Caligiuri,M.A.
  TITLE     Identification of a gene at 11q23 encoding a guanine nucleotide
            exchange factor: evidence for its fusion with MLL in acute myeloid
            leukemia
  JOURNAL   Proc Natl Acad Sci U S A 97 (5), 2145-2150 (2000)
   PUBMED   10681437
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP001150.5, BC063117.1,
            AF180681.1, AK304316.1 and AP000758.5.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_015313.2.
            
            Summary: Rho GTPases play a fundamental role in numerous cellular
            processes that are initiated by extracellular stimuli working
            through G protein-coupled receptors. The encoded protein may form a
            complex with G proteins and stimulate Rho-dependent signals. This
            protein has been observed to form a myeloid/lymphoid fusion partner
            in acute myeloid leukemia. Three transcript variants encoding
            different isoforms have been found for this gene. [provided by
            RefSeq, Jul 2014].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            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 :: AF180681.1, SRR7346977.2307447.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000397843.7/ ENSP00000380942.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-496               AP001150.5         106062-106557
            497-824             BC063117.1         4-331
            825-3125            AF180681.1         1-2301
            3126-4723           AK304316.1         2854-4451
            4724-9436           AF180681.1         3900-8612
            9437-9438           AP000758.5         91617-91618
            9439-10325          AF180681.1         8615-9501
            10326-10326         AP000758.5         92506-92506
FEATURES             Location/Qualifiers
     source          1..10326
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q23.3"
     gene            1..10326
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /note="Rho guanine nucleotide exchange factor 12"
                     /db_xref="GeneID:23365"
                     /db_xref="HGNC:HGNC:14193"
                     /db_xref="MIM:604763"
     exon            1..863
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     CDS             832..5466
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /note="isoform 1 is encoded by transcript variant 1;
                     leukemia-associated rho guanine nucleotide exchange
                     factor; leukemia-associated RhoGEF; Rho guanine nucleotide
                     exchange factor (GEF) 12; KMT2A/ARHGEF12 fusion protein"
                     /codon_start=1
                     /product="rho guanine nucleotide exchange factor 12
                     isoform 1"
                     /protein_id="NP_056128.1"
                     /db_xref="CCDS:CCDS41727.1"
                     /db_xref="GeneID:23365"
                     /db_xref="HGNC:HGNC:14193"
                     /db_xref="MIM:604763"
                     /translation="MSGTQSTITDRFPLKKPIRHGSILNRESPTDKKQKVERIASHDF
                     DPTDSSSKKTKSSSEESRSEIYGLVQRCVIIQKDDNGFGLTVSGDNPVFVQSVKEDGA
                     AMRAGVQTGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVALTVQGRPPGSPQIPLADSE
                     VEPSVIGHMSPIMTSPHSPGASGNMERITSPVLMGEENNVVHNQKVEILRKMLQKEQE
                     RLQLLQEDYNRTPAQRLLKEIQEAKKHIPQLQEQLSKATGSAQDGAVVTPSRPLGDTL
                     TVSEAETDPGDVLGRTDCSSGDASRPSSDNADSPKSGPKERIYLEENPEKSETIQDTD
                     TQSLVGSPSTRIAPHIIGAEDDDFGTEHEQINGQCSCFQSIELLKSRPAHLAVFLHHV
                     VSQFDPATLLCYLYSDLYKHTNSKETRRIFLEFHQFFLDRSAHLKVSVPDEMSADLEK
                     RRPELIPEDLHRHYIQTMQERVHPEVQRHLEDFRQKRSMGLTLAESELTKLDAERDKD
                     RLTLEKERTCAEQIVAKIEEVLMTAQAVEEDKSSTMQYVILMYMKHLGVKVKEPRNLE
                     HKRGRIGFLPKIKQSMKKDKEGEEKGKRRGFPSILGPPRRPSRHDNSAIGRAMELQKA
                     RHPKHLSTPSSVSPEPQDSAKLRQSGLANEGTDAGYLPANSMSSVASGASFSQEGGKE
                     NDTGSKQVGETSAPGDTLDGTPRTLNTVFDFPPPPLDQVQEEECEVERVTEHGTPKPF
                     RKFDSVAFGESQSEDEQFENDLETDPPNWQQLVSREVLLGLKPCEIKRQEVINELFYT
                     ERAHVRTLKVLDQVFYQRVSREGILSPSELRKIFSNLEDILQLHIGLNEQMKAVRKRN
                     ETSVIDQIGEDLLTWFSGPGEEKLKHAAATFCSNQPFALEMIKSRQKKDSRFQTFVQD
                     AESNPLCRRLQLKDIIPTQMQRLTKYPLLLDNIAKYTEWPTEREKVKKAADHCRQILN
                     YVNQAVKEAENKQRLEDYQRRLDTSSLKLSEYPNVEELRNLDLTKRKMIHEGPLVWKV
                     NRDKTIDLYTLLLEDILVLLQKQDDRLVLRCHSKILASTADSKHTFSPVIKLSTVLVR
                     QVATDNKALFVISMSDNGAQIYELVAQTVSEKTVWQDLICRMAASVKEQSTKPIPLPQ
                     STPGEGDNDEEDPSKLKEEQHGISVTGLQSPDRDLGLESTLISSKPQSHSLSTSGKSE
                     VRDLFVAERQFAKEQHTDGTLKEVGEDYQIAIPDSHLPVSEERWALDALRNLGLLKQL
                     LVQQLGLTEKSVQEDWQHFPRYRTASQGPQTDSVIQNSENIKAYHSGEGHMPFRTGTG
                     DIATCYSPRTSTESFAPRDSVGLAPQDSQASNILVMDHMIMTPEMPTMEPEGGLDDSG
                     EHFFDAREAHSDENPSEGDGAVNKEEKDVNLRISGNYLILDGYDPVQESSTDEEVASS
                     LTLQPMTGIPAVESTHQQQHSPQNTHSDGAISPFTPEFLVQQRWGAMEYSCFEIQSPS
                     SCADSQSQIMEYIHKIEADLEHLKKVEESYTILCQRLAGSALTDKHSDKS"
     exon            864..887
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            888..973
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            974..1030
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            1031..1129
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            1130..1179
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            1180..1237
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            1238..1416
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            1417..1494
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            1495..1614
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            1615..1755
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            1756..1830
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            1831..1923
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            1924..2034
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            2035..2133
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            2134..2176
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            2177..2282
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            2283..2420
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            2421..2453
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            2454..2568
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            2569..2674
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            2675..2887
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            2888..3020
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            3021..3056
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            3057..3211
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            3212..3358
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            3359..3444
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            3445..3570
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            3571..3685
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            3686..3786
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            3787..3864
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            3865..3940
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            3941..4108
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            4109..4196
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            4197..4283
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            4284..4363
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            4364..4597
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            4598..5068
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            5069..5385
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            5386..5455
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     exon            5456..10326
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /inference="alignment:Splign:2.1.0"
     regulatory      9400..9405
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /note="hexamer: ATTAAA"
     regulatory      9404..9409
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /note="hexamer: AATAAG"
     polyA_site      9419
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /note="major polyA site"
     polyA_site      9423
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
     regulatory      10302..10307
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
                     /note="hexamer: AATAAA"
     polyA_site      10326
                     /gene="ARHGEF12"
                     /gene_synonym="LARG; PRO2792"
ORIGIN      
        1 agaacccggc gagccggccc tgcgccggga gacgccgccg cctccgcctc ccggaccagg
       61 gcttccaggc cgggccggac gggcatctcc cgcccctcgc ggggagcgtc ggggaggagc
      121 cgccgcctct ggcgattgcg gaagagtccg ggcctcaaag ggatggggag cagtccgcgg
      181 cgctgagaga cccgggtccc tgtcacctcg ggccgcggga cctctccgcc ggcgccagcg
      241 gctcgtccca gcaccgggag cctggtgagg gcggcgagca cagaaggagc cccgggcccg
      301 ggacatggaa tcgcgcgagc ccggcgcggg acggccggag acgcggccaa cgctgcggcc
      361 acgagcagcc ggcagcccca gatagagagc cgggagggag ggccccggcc cttgccgcgg
      421 cggggagttc gaggccccga gactccggag gaggagccga cacccgtccg tgagctgatc
      481 ccgccccagc cccggcggga gtcccgggtc cccttcccac tgcgcgcgga tttccctctc
      541 tgaggaagtt tatccttgtg ccttctggag gatttctctc tagctcgact cactctggac
      601 tgactcgctc cctggctttc tcagttcgtt ttgggagata acttgttttg ctccaagccg
      661 catccgttga ccccttacag tcggatggtc tagatgactg aatggagttt tgagttggac
      721 ttttgtgtcc ctgacggagt tgggcctgat cccagagcac tgggggtggg gaggaggtgt
      781 tactgtaaaa tgcaagttgg ataaaaggag gacctctcgc caagggcccc aatgagtggc
      841 acacagtcta ctatcaccga caggtttccc ctcaaaaaac ctataaggca tggaagtatt
      901 ttgaaccgag agtcaccaac agataagaag cagaaagttg agcgcattgc atcacatgat
      961 tttgacccca cagatagctc ctccaagaag acaaagtcta gttcagagga gagtagatcc
     1021 gagatatatg gtcttgttca gcgttgcgta atcatccaga aagatgacaa tggatttggg
     1081 ctgacggtca gtggagacaa tccagtcttc gtacagtctg tcaaagaaga tggagcagcc
     1141 atgcgggctg gagtacagac aggtgatcga atcatcaagg tgaatggaac tctggtgact
     1201 cattcaaatc atctggaggt ggtgaagcta atcaaatctg gttcctatgt agctctcact
     1261 gttcagggac gcccacctgg gtcgccccag attccacttg ccgactctga agtagagccg
     1321 tcagtcattg gacatatgtc tcccatcatg acatctcctc attcacctgg agcatctggg
     1381 aatatggaga gaatcactag tcctgtgctc atgggggagg aaaacaatgt ggttcataac
     1441 cagaaagtag aaattctgag aaaaatgtta cagaaagaac aggaacggct acagttattg
     1501 caggaagatt acaaccgaac acctgcccaa agattgctaa aagagatcca agaggccaag
     1561 aaacacattc ctcagctgca agagcagtta tccaaagcca caggctctgc tcaggatgga
     1621 gctgtagtta caccctccag acctttaggg gacaccctaa cagtcagtga ggcagaaaca
     1681 gatcctggag atgtactggg caggactgac tgtagcagtg gagatgcttc tcggcccagt
     1741 agtgacaatg cagatagtcc caagagtggc ccaaaagaga gaatttatct agaggaaaac
     1801 ccagagaaaa gtgaaacaat tcaggacact gacactcaat cacttgtcgg aagtccctca
     1861 acccgtatag cacctcatat tattggagca gaagatgatg attttggtac tgaacatgaa
     1921 cagatcaatg gacagtgcag ctgtttccag agcattgaat tactaaaatc tcgcccggct
     1981 catttggctg ttttcttaca ccatgtagtt tcacaatttg accctgcgac tttgctctgt
     2041 tatctctatt cagacctgta taaacatacc aattccaaag aaactcgtcg catcttcctt
     2101 gagtttcatc agttctttct agatcgatca gcacacctga aagtttctgt tcctgatgaa
     2161 atgtctgcag atctagaaaa gagaagacct gagctcattc ctgaggatct gcatcgccac
     2221 tatatccaaa ctatgcaaga aagagtccat ccagaagttc aaaggcactt agaagatttt
     2281 cggcagaaac gtagtatggg actgaccttg gctgaaagcg agctgactaa acttgatgca
     2341 gagcgagaca aggaccgatt gactttggag aaggagcgga catgtgcaga acagattgtt
     2401 gccaaaattg aagaagtatt gatgactgct caggctgtag aggaagataa gagctccacc
     2461 atgcagtatg ttattctcat gtatatgaag catttgggag taaaagtgaa agagcctcga
     2521 aatttggagc acaaacgggg tcggattgga tttcttccca aaatcaagca aagtatgaag
     2581 aaagataaag aaggggaaga aaaagggaag cgaagaggat tccccagcat cctgggaccc
     2641 ccacggagac caagccgtca tgacaacagt gcaattggca gagccatgga actacagaag
     2701 gcgcgccacc ctaagcactt atccacaccc tcatctgtga gtcctgaacc tcaggactct
     2761 gccaagttgc gccagagtgg gttagcaaat gaaggaacag acgctggata cctgcctgcc
     2821 aattccatgt cttctgtagc ttcaggggcc tctttttccc aggaaggagg gaaagagaat
     2881 gatacaggat caaagcaagt tggagaaaca tcagcacctg gagacacctt agatggcaca
     2941 cctcgtactc tcaatactgt ctttgatttc ccaccacctc cattagacca agtgcaggag
     3001 gaggaatgtg aagtagaaag ggtgactgaa catgggacac caaagccctt tcgaaagttt
     3061 gacagtgtag cttttggaga aagtcaaagt gaggatgaac aatttgaaaa tgacttagag
     3121 acagatccac ccaactggca gcagcttgtt agtcgagaag tgttactggg actaaaacct
     3181 tgtgaaatca aaagacagga agtgattaat gaattgttct acactgaaag agctcatgtt
     3241 cgaacactga aggttcttga tcaagtgttc tatcagcgag tatccagaga aggaattctg
     3301 tcaccctcag agctacggaa aattttttca aacttggaag atattcttca acttcatatt
     3361 ggattgaatg aacaaatgaa ggctgttcga aagagaaatg agacctctgt tatcgatcag
     3421 attggggaag atttgctgac atggttcagc ggaccaggag aggagaaatt gaaacatgct
     3481 gctgctacct tttgcagtaa ccaacctttc gccctggaaa tgatcaaatc tcgtcagaaa
     3541 aaggattctc gatttcagac ttttgtgcaa gatgctgaaa gtaatccact gtgtcgtcgt
     3601 cttcaactga aggatattat tcccactcaa atgcaaaggc ttactaagta cccacttctg
     3661 ttggataata ttgccaaata cacagaatgg ccaacagaaa gggagaaggt gaagaaagct
     3721 gcagatcact gtcgtcagat cttaaattat gtaaatcagg ctgtcaagga ggcagaaaac
     3781 aagcagcgcc tagaagatta tcagcgtcgc cttgatacct ccagcctgaa gttgtcagag
     3841 tacccaaatg ttgaagagct caggaatttg gatttaacaa aaaggaagat gattcatgaa
     3901 gggccattgg tttggaaggt gaatagagat aaaactattg atttatacac gttgctgctg
     3961 gaagacattc ttgtattgtt acaaaagcag gatgatagac tggttttaag gtgtcatagt
     4021 aagattctgg catctacagc tgatagcaaa cacacgttta gccctgtcat taagttgagt
     4081 acagtgttgg ttcgacaagt ggcaacagat aacaaagctt tattcgtcat ttccatgtca
     4141 gacaatggcg ctcagattta tgaactggtg gcacagacag tttctgaaaa gactgtctgg
     4201 caggacctaa tctgtcggat ggctgcatca gtgaaggagc aatccacaaa gccaattcca
     4261 ttaccacagt caacacctgg cgaaggagat aatgatgaag aagatccttc aaaattaaaa
     4321 gaggagcagc atggcatttc agtcactggt ttgcagagtc cagacagaga tttgggatta
     4381 gaatctacct taatatcgtc aaaacctcag tctcattcac tgagtacctc tgggaaatca
     4441 gaggtacgtg atctgtttgt ggctgagaga cagtttgcaa aggaacaaca tacagatggg
     4501 acactaaagg aagttggaga agattatcaa atcgcaatcc cagattcaca cctgcctgtc
     4561 tcagaagaac ggtgggcatt ggatgcacta agaaatttgg gtttgttgaa gcagttgctg
     4621 gtgcaacagc taggtttgac tgagaagagc gttcaggaag actggcaaca tttcccaaga
     4681 tacagaacag cctctcaggg gccgcagaca gacagtgtca tccagaactc tgaaaatatt
     4741 aaggcctatc attctggtga aggacatatg ccctttagaa ctggaactgg tgacattgca
     4801 acttgttaca gtccacggac ttcaactgaa tcttttgctc cacgggattc agtgggactg
     4861 gcaccccagg atagccaggc aagtaacatt ttagtaatgg accacatgat tatgacccca
     4921 gagatgccta ccatggagcc agaagggggt cttgatgaca gtggagagca cttttttgat
     4981 gcccgtgaag cacatagtga tgagaatcca tcagaaggtg atggagcagt taacaaggaa
     5041 gagaaggatg ttaatttacg catctcagga aactatttga tccttgatgg ctatgaccca
     5101 gtgcaggaga gttccacaga tgaggaggtt gcttcctcac ttaccctgca gcccatgaca
     5161 ggcatccctg ctgtggaatc cacccaccag cagcaacatt ctcctcagaa tactcactcc
     5221 gatggggcaa tttcaccatt cacccccgaa tttctggtcc agcagcgctg gggagctatg
     5281 gagtattcct gttttgagat ccagagtccc tcctcttgtg cagattcaca gagccagatc
     5341 atggagtaca ttcataagat agaggctgac cttgaacact taaagaaggt ggaggaaagt
     5401 tacaccattc tttgccaaag gctggctgga tcagccctca cagacaagca ctcagataaa
     5461 agttagagcc gcatgtcctg gaggtgactg caggttgttg gatttggagt atcggccgtg
     5521 tctcaccaca tcctggctcc agtgtggatg cagagagagt gtgacagagg atctgcctgt
     5581 gaaccacctg ggattagtca agtcccaagg tgcccagagt gggactagtt cttcacagtg
     5641 tggcagctgc actaatctgt ttgtgaggga atatccattc cctcactcta ctctcctcac
     5701 tatcggaaat tcattttgat tcagaataaa aaccaaatgt atagagcttt gggtgtagga
     5761 tatgaaattg tacttagatt taagaaaaag agaaaatcag atgtatttat ttgacttcat
     5821 tccgtatttg aaagcacatt ttaattttta tttgccttgt tttgttttaa ttgagtagtg
     5881 agagttttag acctttgtct ttagtacacc caaggatcaa ctgctcctga agcaaagagg
     5941 tcaggatgga gtatgcagaa gttgggtaga gaggttaaga agaggaggaa gtgagacggg
     6001 gaagggagga gcaccttgct tcactataca gtattccaag ctctctgctg tccagtaggc
     6061 tgcttctctg agggtcacct caaaggtatg ctatgccgtg tggctcttat gtgcccaggt
     6121 ggtgtggtca gagagtggat gggcttcctc ccgccctgag gcaagcacct cttctctgta
     6181 gctgggatca accacaatta ataggaatcc tcaacatact aaatagcagg cacttgaaaa
     6241 tgggtgtgtt ttcttccatt gtcgtctttt ctattgaggg ttgggatttg ggtgggagag
     6301 gaaagcaaat tttattttct tgactataaa tttgttattc ttggtatcat ttcattttta
     6361 taattataca ttagacattg gcacttgtgt aaaactgtcc ctgcagattg agcaggaagt
     6421 aaaaacaaat ggaaatgctt cggatagtgg caggggtggg ggttgctaag gaaagggtgg
     6481 gatgggagtg ggtaaagagt ttgggaaggt tatctaactg aatcactact gagttgaatc
     6541 atggctatca ttagccacag gtactgctga ttataaggcc agtaaaattt tagtacctgg
     6601 aggtttgact ctaatttttg cactgatggt gccaaagggc cctgagtcaa aaggatagcc
     6661 aagggtggag tggaaaaaga tatggtgaag gcagaactgc tcacaccagc tccagaagca
     6721 cgtcctctga cttcactgcc gcagctcttt ccacacgggg ccgtgattga ccctaaaaat
     6781 tgcagaccag cacatacact ggacactgca ggcaaggtgt tggtaactgc ctgctctagg
     6841 atgaatagta gcgttagcag caccctacag agggtaagtt tcagaattgt aatttgagaa
     6901 ctccttcaat tatattgact ttctttggtt ttccttgtgc attaggtata tattttttga
     6961 agtatttttg ccaactaaaa tgaagtctgt aaattctgtt aataaacaag gagttcatcc
     7021 gttgctcaca tctttcattg gtgccctctg aactctgtgg gttgctagga tgtaatttta
     7081 atgcttccct gcagtccaaa gatgattttt tcaccacaaa tggtaaggga tgcccaccta
     7141 cttttataaa caccactgca acttaacaag tttatttatc tatgtccaga tttctgtttc
     7201 tgtcctaaat tgatctgtgt ttttaggtgg atcaacttgg atctttagac ctcatctata
     7261 aattgaaatt atatttttag tcataagcca agtacaatct aactcagaat gggattaaaa
     7321 attttagaag cagaagctaa tatataaatg aagtttggga tttggaactt tctgtatctc
     7381 ttaggaggaa caagtaaaaa ccaaatggtt acattgtgct gctagaaata atgtcattct
     7441 caattaaaag ggttacacct gtagccactt gacactaaca ccatcgaggg caattaatca
     7501 ggagaaaagt aaatataaaa actttgctct taacgtcaca cactacaggg taattatgta
     7561 attctctagc actcaattaa gaagcttgta ggttagcaaa atttcagttt ctctagttca
     7621 gccagtgtct tgtccttagt aattatttgc tttccctgca gttcaatttc tccttggaac
     7681 tctaacagga ctaactggaa aaatactttg accatagctc tagtacttcc aaataaattc
     7741 atatctagat tttcaaacaa agccccaaga tgaagtctaa ttctgaaaat atctcacaat
     7801 ttttgaatgt tctttttatc ttaccgacct aacttctctt ttccctccca acttggcctc
     7861 ccacacgttc catttcattt tggccattat agtcacatcc gtttgacttt ggttgtgaca
     7921 tcttcctttc aggatgatgg aattagatgc agtctgtctt tgagtgagac tggtcaccat
     7981 cagaggagtt ttttctaagt gacgtgacta gaagttgaaa tctacttccc tgctaaaggg
     8041 cacaggggtg gtgtacaaag aaagctacct tcccagagca agcaggctgc attttagcta
     8101 tggaagtgac ctgctgtgac actgtgctct cttctgtggg cttaatggtt cctttgctat
     8161 gaagtggcaa attacatgta gagtgtctcc ttccttttca gagaacagtt aatcaaggca
     8221 aatcagcaag cccccaaagt gctgtaattt aacatcatga ttaccacctt cgaagctata
     8281 tattttgcat actttaaaat cacctaactt ggactgcttg aattacattg gcttttagaa
     8341 ccgaaattgt aactatgtat tgtatttcat gggaggtata ttttatgagc tttttggctt
     8401 tcttttttcc cacagcaact gccaatgaag gatgaatccc ctttttaaaa agttgttgtt
     8461 gttgttgttt atttgatttt gagttaggag ggataataga gaagtccatt taaaaattat
     8521 ttttagaagc taaagaaagt aattatgctt cctgtgaatt gtcttttact ggcatctttg
     8581 ttttcctctt tgatgttagt aaatttggtg taatacgtgg ggcttccata tttcaaagtg
     8641 gaagctttct tctctgaagt cgatatatgg ttttgaatta ctagagcttt ggtcagtatt
     8701 tccttcccta tatgtcacag agggcaccac tgagaactgc gtgcatagga cctcaaaata
     8761 caaaattagc agggcctcac agtcagcttc ctcatggcta gtttttcccc cttatattac
     8821 aatttttgtt ttataagtca tttttttcct gatatttcca ccacttttca gagtcatcta
     8881 caaaattttt ctttcctcaa gaaaagagtt ccttttgcct tattccttat gccttcccca
     8941 ctggtattga gggttttgat aataaattgg taggaaaaaa aagtacctcc tagaaggaag
     9001 ccttccccac catttccagg tgccaactgc taagcagata tattccaaaa atggtaactg
     9061 tcatgtgcac actgttggtt atttttaata agcctcttcc tactagaaca ttttattttc
     9121 cttgttcacc atacaatcat gtactcttta acagaaattg cttttaaaaa atatctggaa
     9181 ctatctttaa aaaaacttta ttaataatca tgtattttta ctgatcacat tttgaaatgc
     9241 ctaaaagact ttattgttct aattatccag atgtaccttt gtaaaatagc tcttttatga
     9301 attagctgat aaggctgtat gtttctggaa caaaatattg gtcatctaaa aactttctgt
     9361 tttctggggt ctgggaaaat agaaaataag atttcaaata ttaaataagc ttaaaggaac
     9421 caagcatgtg actttttatt tgtattctgg ttgatttgtc ttgtccaagt tatattagaa
     9481 aagttgagga gtcgaggagc ctgtaattaa ttttcctgtc agtgactgtc agacatcttc
     9541 ctgcttatta gagcatccct agcaacaagg ctaaaccttc atgacagtgc tggcaggtgg
     9601 gcttgcccta gcatgtgggg caggtttgtt gtttttttaa tagctttatt gagatattca
     9661 catatcatat aattcatcca tttaaagtgt ataatcagat gggttttggt atattattga
     9721 tttttaattg tggtgaaata tatatataac aaaatttgct attgtaacta tttttaagta
     9781 taaagttcag tgaggtaggc cagcttttat gacgcacctg aagataactt tggttttaat
     9841 cctaccctaa atgaagcata tgcctctatt tttcctgtcc ccagtgctgg gcttcttcac
     9901 ataccaacat ttctgtgctt ttaccaacag cattttagct cagaaggctc gcttactttg
     9961 ggcatttgct gtattttggt tttgaaatac ttgtaatttg acttattctt gggataatat
    10021 tttagttttc agtcattcaa gggcacattt ggctgacgga gctaataagc gtaataaaat
    10081 gcttagtagt ttataccatc ttttagttaa acattttaaa gattaagact attcaaatgt
    10141 actttgcgga aattaacctg tttgtatgcc tggctttgtt tacaaacata tatctatatc
    10201 tatatatata gatacagata cagatacata tctggtggaa caaagaaata cctgtaccat
    10261 tcccacttgc tctttgatag ccacctccta ggaatggaga caataaaact ctgtatttgc
    10321 atgtga
//
