LOCUS       NM_005406               9446 bp    mRNA    linear   PRI 29-OCT-2024
DEFINITION  Homo sapiens Rho associated coiled-coil containing protein kinase 1
            (ROCK1), mRNA.
ACCESSION   NM_005406 XM_001713904 XM_001722015 XM_001723570
VERSION     NM_005406.3
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 9446)
  AUTHORS   Hu,F., Zhao,L., Wang,J., Li,X., Xue,Z., Ma,Y., Zheng,M., Chen,C.,
            Tong,M., Guo,X., Li,H., Jin,H., Xie,Q., Zhang,X., Huang,C. and
            Huang,H.
  TITLE     TRIM40 interacts with ROCK1 directly and inhibits colorectal cancer
            cell proliferation through the c-Myc/p21 axis
  JOURNAL   Biochim Biophys Acta Mol Cell Res 1871 (8), 119855 (2024)
   PUBMED   39357549
  REMARK    GeneRIF: TRIM40 interacts with ROCK1 directly and inhibits
            colorectal cancer cell proliferation through the c-Myc/p21 axis.
REFERENCE   2  (bases 1 to 9446)
  AUTHORS   Ren,C., Xi,L., Li,H., Pan,Z., Li,Y., Wang,G., Dai,J., He,D., Fan,S.
            and Wang,Q.
  TITLE     Inhibition of the FOXO1-ROCK1 axis mitigates cardiomyocyte injury
            under chronic hypoxia in Tetralogy of Fallot by maintaining
            mitochondrial quality control
  JOURNAL   Life Sci 357, 123084 (2024)
   PUBMED   39374570
  REMARK    GeneRIF: Inhibition of the FOXO1-ROCK1 axis mitigates cardiomyocyte
            injury under chronic hypoxia in Tetralogy of Fallot by maintaining
            mitochondrial quality control.
REFERENCE   3  (bases 1 to 9446)
  AUTHORS   Li,H., Han,X., Song,L., Li,X., Zhang,L., Jin,Z., Zhang,Y., Wang,T.,
            Huang,Z., Jia,Z. and Yang,J.
  TITLE     LINC00645 inhibits renal cell carcinoma progression by interacting
            with HNRNPA2B1 to regulate the ROCK1 mRNA stability
  JOURNAL   Gene 905, 148232 (2024)
   PUBMED   38309317
  REMARK    GeneRIF: LINC00645 inhibits renal cell carcinoma progression by
            interacting with HNRNPA2B1 to regulate the ROCK1 mRNA stability.
REFERENCE   4  (bases 1 to 9446)
  AUTHORS   Zhang,Y., Li,N. and Kobayashi,S.
  TITLE     Paxillin participates in the sphingosylphosphorylcholine-induced
            abnormal contraction of vascular smooth muscle by regulating
            Rho-kinase activation
  JOURNAL   Cell Commun Signal 22 (1), 58 (2024)
   PUBMED   38254202
  REMARK    GeneRIF: Paxillin participates in the
            sphingosylphosphorylcholine-induced abnormal contraction of
            vascular smooth muscle by regulating Rho-kinase activation.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 9446)
  AUTHORS   Maas-Bauer,K., Stell,A.V., Yan,K.L., de Vega,E., Vinnakota,J.M.,
            Unger,S., Nunez,N., Norona,J., Talvard-Balland,N., Kossmann,S.,
            Schwan,C., Miething,C., Martens,U.S., Shoumariyeh,K., Nestor,R.P.,
            Duquesne,S., Hanke,K., Rackiewicz,M., Hu,Z., El Khawanky,N.,
            Taromi,S., Andrlova,H., Faraidun,H., Walter,S., Pfeifer,D.,
            Follo,M., Waldschmidt,J., Melchinger,W., Rassner,M., Wehr,C.,
            Schmitt-Graeff,A., Halbach,S., Liao,J., Hacker,G., Brummer,T.,
            Dengjel,J., Andrieux,G., Grosse,R., Tugues,S., Blazar,B.R.,
            Becher,B., Boerries,M. and Zeiser,R.
  TITLE     ROCK1/2 signaling contributes to corticosteroid-refractory acute
            graft-versus-host disease
  JOURNAL   Nat Commun 15 (1), 446 (2024)
   PUBMED   38199985
  REMARK    GeneRIF: ROCK1/2 signaling contributes to corticosteroid-refractory
            acute graft-versus-host disease.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 9446)
  AUTHORS   Fujisawa,K., Fujita,A., Ishizaki,T., Saito,Y. and Narumiya,S.
  TITLE     Identification of the Rho-binding domain of p160ROCK, a
            Rho-associated coiled-coil containing protein kinase
  JOURNAL   J Biol Chem 271 (38), 23022-23028 (1996)
   PUBMED   8798490
REFERENCE   7  (bases 1 to 9446)
  AUTHORS   Ishizaki,T., Maekawa,M., Fujisawa,K., Okawa,K., Iwamatsu,A.,
            Fujita,A., Watanabe,N., Saito,Y., Kakizuka,A., Morii,N. and
            Narumiya,S.
  TITLE     The small GTP-binding protein Rho binds to and activates a 160 kDa
            Ser/Thr protein kinase homologous to myotonic dystrophy kinase
  JOURNAL   EMBO J 15 (8), 1885-1893 (1996)
   PUBMED   8617235
REFERENCE   8  (bases 1 to 9446)
  AUTHORS   Tsujimura,K., Tanaka,J., Ando,S., Matsuoka,Y., Kusubata,M.,
            Sugiura,H., Yamauchi,T. and Inagaki,M.
  TITLE     Identification of phosphorylation sites on glial fibrillary acidic
            protein for cdc2 kinase and Ca(2+)-calmodulin-dependent protein
            kinase II
  JOURNAL   J Biochem 116 (2), 426-434 (1994)
   PUBMED   7822264
REFERENCE   9  (bases 1 to 9446)
  AUTHORS   Tokui,T., Yamauchi,T., Yano,T., Nishi,Y., Kusagawa,M., Yatani,R.
            and Inagaki,M.
  TITLE     Ca2(+)-calmodulin-dependent protein kinase II phosphorylates
            various types of non-epithelial intermediate filament proteins
  JOURNAL   Biochem Biophys Res Commun 169 (3), 896-904 (1990)
   PUBMED   2114109
REFERENCE   10 (bases 1 to 9446)
  AUTHORS   Inagaki,M., Gonda,Y., Nishizawa,K., Kitamura,S., Sato,C., Ando,S.,
            Tanabe,K., Kikuchi,K., Tsuiki,S. and Nishi,Y.
  TITLE     Phosphorylation sites linked to glial filament disassembly in vitro
            locate in a non-alpha-helical head domain
  JOURNAL   J Biol Chem 265 (8), 4722-4729 (1990)
   PUBMED   2155236
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK057038.1, U43195.1,
            AU121527.1 and AC036178.11.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_005406.2.
            
            Summary: This gene encodes a protein serine/threonine kinase that
            is activated when bound to the GTP-bound form of Rho. The small
            GTPase Rho regulates formation of focal adhesions and stress fibers
            of fibroblasts, as well as adhesion and aggregation of platelets
            and lymphocytes by shuttling between the inactive GDP-bound form
            and the active GTP-bound form. Rho is also essential in cytokinesis
            and plays a role in transcriptional activation by serum response
            factor. This protein, a downstream effector of Rho, phosphorylates
            and activates LIM kinase, which in turn, phosphorylates cofilin,
            inhibiting its actin-depolymerizing activity. A pseudogene, related
            to this gene, is also located on chromosome 18. [provided by
            RefSeq, Aug 2015].
            
            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 :: SRR14372080.3813839.1,
                                           SRR14038197.418539.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000399799.3/ ENSP00000382697.1
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-903               AK057038.1         40-942
            904-4964            U43195.1           1-4061
            4965-5406           AU121527.1         206-647
            5407-6612           AC036178.11        18803-20008         c
            6613-9446           AC036178.11        15969-18802         c
FEATURES             Location/Qualifiers
     source          1..9446
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="18"
                     /map="18q11.1"
     gene            1..9446
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /note="Rho associated coiled-coil containing protein
                     kinase 1"
                     /db_xref="GeneID:6093"
                     /db_xref="HGNC:HGNC:10251"
                     /db_xref="MIM:601702"
     exon            1..996
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     CDS             904..4968
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /EC_number="2.7.11.1"
                     /note="renal carcinoma antigen NY-REN-35; p160 ROCK-1"
                     /codon_start=1
                     /product="rho-associated protein kinase 1"
                     /protein_id="NP_005397.1"
                     /db_xref="CCDS:CCDS11870.2"
                     /db_xref="GeneID:6093"
                     /db_xref="HGNC:HGNC:10251"
                     /db_xref="MIM:601702"
                     /translation="MSTGDSFETRFEKMDNLLRDPKSEVNSDCLLDGLDALVYDLDFP
                     ALRKNKNIDNFLSRYKDTINKIRDLRMKAEDYEVVKVIGRGAFGEVQLVRHKSTRKVY
                     AMKLLSKFEMIKRSDSAFFWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEYMPGGD
                     LVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFG
                     TCMKMNKEGMVRCDTAVGTPDYISPEVLKSQGGDGYYGRECDWWSVGVFLYEMLVGDT
                     PFYADSLVGTYSKIMNHKNSLTFPDDNDISKEAKNLICAFLTDREVRLGRNGVEEIKR
                     HLFFKNDQWAWETLRDTVAPVVPDLSSDIDTSNFDDLEEDKGEEETFPIPKAFVGNQL
                     PFVGFTYYSNRRYLSSANPNDNRTSSNADKSLQESLQKTIYKLEEQLHNEMQLKDEME
                     QKCRTSNIKLDKIMKELDEEGNQRRNLESTVSQIEKEKMLLQHRINEYQRKAEQENEK
                     RRNVENEVSTLKDQLEDLKKVSQNSQLANEKLSQLQKQLEEANDLLRTESDTAVRLRK
                     SHTEMSKSISQLESLNRELQERNRILENSKSQTDKDYYQLQAILEAERRDRGHDSEMI
                     GDLQARITSLQEEVKHLKHNLEKVEGERKEAQDMLNHSEKEKNNLEIDLNYKLKSLQQ
                     RLEQEVNEHKVTKARLTDKHQSIEEAKSVAMCEMEKKLKEEREAREKAENRVVQIEKQ
                     CSMLDVDLKQSQQKLEHLTGNKERMEDEVKNLTLQLEQESNKRLLLQNELKTQAFEAD
                     NLKGLEKQMKQEINTLLEAKRLLEFELAQLTKQYRGNEGQMRELQDQLEAEQYFSTLY
                     KTQVKELKEEIEEKNRENLKKIQELQNEKETLATQLDLAETKAESEQLARGLLEEQYF
                     ELTQESKKAASRNRQEITDKDHTVSRLEEANSMLTKDIEILRRENEELTEKMKKAEEE
                     YKLEKEEEISNLKAAFEKNINTERTLKTQAVNKLAEIMNRKDFKIDRKKANTQDLRKK
                     EKENRKLQLELNQEREKFNQMVVKHQKELNDMQAQLVEECAHRNELQMQLASKESDIE
                     QLRAKLLDLSDSTSVASFPSADETDGNLPESRIEGWLSVPNRGNIKRYGWKKQYVVVS
                     SKKILFYNDEQDKEQSNPSMVLDIDKLFHVRPVTQGDVYRAETEEIPKIFQILYANEG
                     ECRKDVEMEPVQQAEKTNFQNHKGHEFIPTLYHFPANCDACAKPLWHVFKPPPALECR
                     RCHVKCHRDHLDKKEDLICPCKVSYDVTSARDMLLLACSQDEQKKWVTHLVKKIPKNP
                     PSGFVRASPRTLSTRSTANQSFRKVVKNTSGKTS"
     exon            997..1078
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            1079..1179
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            1180..1317
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            1318..1493
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            1494..1578
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            1579..1723
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            1724..1862
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            1863..1954
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            1955..2114
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            2115..2175
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            2176..2264
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            2265..2313
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            2314..2449
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            2450..2541
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            2542..2788
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            2789..2895
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            2896..3046
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            3047..3207
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            3208..3392
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            3393..3462
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            3463..3557
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            3558..3723
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            3724..3817
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            3818..3906
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            3907..4095
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            4096..4255
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            4256..4326
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            4327..4415
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            4416..4494
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            4495..4756
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            4757..4964
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     exon            4965..9446
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /inference="alignment:Splign:2.1.0"
     regulatory      6401..6406
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /note="hexamer: AATAAA"
     polyA_site      6425
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /note="major polyA site"
     regulatory      6586..6591
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /note="hexamer: ATTAAA"
     polyA_site      6612
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
     regulatory      9358..9363
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /note="hexamer: AATAAA"
     polyA_site      9381
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
     regulatory      9385..9390
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /note="hexamer: TATAAA"
     polyA_site      9408
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
     regulatory      9424..9429
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
                     /note="hexamer: ATTAAA"
     polyA_site      9446
                     /gene="ROCK1"
                     /gene_synonym="P160ROCK; ROCK-I"
ORIGIN      
        1 agtctgcccc ggcggtctcc gtttgtttga acaggaaggc ggacatatta gtccctctca
       61 gcccccctcg ccccaccccc caggcattcg ccgccgcgac tcgccctttc cccggctggg
      121 accgcagccc ctcccagaag ctcccccatc agcagccgcc gggacccaac tatcgtcttc
      181 ctcttcgccc gctctccagc ctttcctctg ctaagtctcc atcgggcatc gacctcgccc
      241 tgccccaccg gacaccgtag cagcagcccc agcagcgacg ggacaaaatg ggagagtgag
      301 gctgtcctgc gtggaccagc tcgtggccga gactgatcgg tgcgtcgggc cgggccgagt
      361 agagccgggg acgcggggct agaccgtcta cagcgcctct gagcggagcg ggcccggccc
      421 gtggcccgag cggcggccgc agctggcaca gctcctcacc cgccctttgc tttcgccttt
      481 cctcttctcc ctcccttgtt gcccggaggg agtctccacc ctgcttctct ttctctaccc
      541 gctcctgccc atctcgggac ggggacccct ccatggcgac ggcggccggg gcccgctaga
      601 ctgaagcacc tcgccggagc gacgaggctg gtggcgacgg cgctgtcggc tgtcgtgagg
      661 ggctgccggg tgggatgcga ctttgggcgt ccgagcggct gtgggtcgct gttgcccccg
      721 gcccggggtc tggagagcgg aggtcccctc agtgagggga agacggggga accgggcgca
      781 cctggtgacc ctgaggttcc ggctcctccg ccccgcggct gcgaacccac cgcggaggaa
      841 gttggttgaa attgctttcc gctgctggtg ctggtaagag ggcattgtca cagcagcagc
      901 aacatgtcga ctggggacag ttttgagact cgatttgaaa aaatggacaa cctgctgcgg
      961 gatcccaaat cggaagtgaa ttcggattgt ttgctggatg gattggatgc tttggtatat
     1021 gatttggatt ttcctgcctt aagaaaaaac aaaaatattg acaacttttt aagcagatat
     1081 aaagacacaa taaataaaat cagagattta cgaatgaaag ctgaagatta tgaagtagtg
     1141 aaggtgattg gtagaggtgc atttggagaa gttcaattgg taaggcataa atccaccagg
     1201 aaggtatatg ctatgaagct tctcagcaaa tttgaaatga taaagagatc tgattctgct
     1261 tttttctggg aagaaaggga catcatggct tttgccaaca gtccttgggt tgttcagctt
     1321 ttttatgcat tccaagatga tcgttatctc tacatggtga tggaatacat gcctggtgga
     1381 gatcttgtaa acttaatgag caactatgat gtgcctgaaa aatgggcacg attctatact
     1441 gcagaagtag ttcttgcatt ggatgcaatc cattccatgg gttttattca cagagatgtg
     1501 aagcctgata acatgctgct ggataaatct ggacatttga agttagcaga ttttggtact
     1561 tgtatgaaga tgaataagga aggcatggta cgatgtgata cagcggttgg aacacctgat
     1621 tatatttccc ctgaagtatt aaaatcccaa ggtggtgatg gttattatgg aagagaatgt
     1681 gactggtggt cggttggggt atttttatac gaaatgcttg taggtgatac acctttttat
     1741 gcagattctt tggttggaac ttacagtaaa attatgaacc ataaaaattc acttaccttt
     1801 cctgatgata atgacatatc aaaagaagca aaaaacctta tttgtgcctt ccttactgac
     1861 agggaagtga ggttagggcg aaatggtgta gaagaaatca aacgacatct cttcttcaaa
     1921 aatgaccagt gggcttggga aacgctccga gacactgtag caccagttgt acccgattta
     1981 agtagtgaca ttgatactag taattttgat gacttggaag aagataaagg agaggaagaa
     2041 acattcccta ttcctaaagc tttcgttggc aatcaactac cttttgtagg atttacatat
     2101 tatagcaatc gtagatactt atcttcagca aatcctaatg ataacagaac tagctccaat
     2161 gcagataaaa gcttgcagga aagtttgcaa aaaacaatct ataagctgga agaacagctg
     2221 cataatgaaa tgcagttaaa agatgaaatg gagcagaagt gcagaacctc aaacataaaa
     2281 ctagacaaga taatgaaaga attggatgaa gagggaaatc aaagaagaaa tctagaatct
     2341 acagtgtctc agattgagaa ggagaaaatg ttgctacagc atagaattaa tgagtaccaa
     2401 agaaaagctg aacaggaaaa tgagaagaga agaaatgtag aaaatgaagt ttctacatta
     2461 aaggatcagt tggaagactt aaagaaagtc agtcagaatt cacagcttgc taatgagaag
     2521 ctgtcccagt tacaaaagca gctagaagaa gccaatgact tacttaggac agaatcggac
     2581 acagctgtaa gattgaggaa gagtcacaca gagatgagca agtcaattag tcagttagag
     2641 tccctgaaca gagagttgca agagagaaat cgaattttag agaattctaa gtcacaaaca
     2701 gacaaagatt attaccagct gcaagctata ttagaagctg aacgaagaga cagaggtcat
     2761 gattctgaga tgattggaga ccttcaagct cgaattacat ctttacaaga ggaggtgaag
     2821 catctcaaac ataatctcga aaaagtggaa ggagaaagaa aagaggctca agacatgctt
     2881 aatcactcag aaaaggaaaa gaataattta gagatagatt taaactacaa acttaaatca
     2941 ttacaacaac ggttagaaca agaggtaaat gaacacaaag taaccaaagc tcgtttaact
     3001 gacaaacatc aatctattga agaggcaaag tctgtggcaa tgtgtgagat ggaaaaaaag
     3061 ctgaaagaag aaagagaagc tcgagagaag gctgaaaatc gggttgttca gattgagaaa
     3121 cagtgttcca tgctagacgt tgatctgaag caatctcagc agaaactaga acatttgact
     3181 ggaaataaag aaaggatgga ggatgaagtt aagaatctaa ccctgcaact ggagcaggaa
     3241 tcaaataagc ggctgttgtt acaaaatgaa ttgaagactc aagcatttga ggcagacaat
     3301 ttaaaaggtt tagaaaagca gatgaaacag gaaataaata ctttattgga agcaaagaga
     3361 ttattagaat ttgagttagc tcagcttacg aaacagtata gaggaaatga aggacagatg
     3421 cgggagctac aagatcagct tgaagctgag caatatttct cgacacttta taaaacccag
     3481 gtaaaggaac ttaaagaaga aattgaagaa aaaaacagag aaaatttaaa gaaaatacag
     3541 gaactacaaa atgaaaaaga aactcttgct actcagttgg atctagcaga aacaaaagct
     3601 gagtctgagc agttggcgcg aggccttctg gaagaacagt attttgaatt gacgcaagaa
     3661 agcaagaaag ctgcttcaag aaatagacaa gagattacag ataaagatca cactgttagt
     3721 cggcttgaag aagcaaacag catgctaacc aaagatattg aaatattaag aagagagaat
     3781 gaagagctaa cagagaaaat gaagaaggca gaggaagaat ataaactgga gaaggaggag
     3841 gagatcagta atcttaaggc tgcctttgaa aagaatatca acactgaacg aacccttaaa
     3901 acacaggctg ttaacaaatt ggcagaaata atgaatcgaa aagattttaa aattgataga
     3961 aagaaagcta atacacaaga tttgagaaag aaagaaaagg aaaatcgaaa gctgcaactg
     4021 gaactcaacc aagaaagaga gaaattcaac cagatggtag tgaaacatca gaaggaactg
     4081 aatgacatgc aagcgcaatt ggtagaagaa tgtgcacata ggaatgagct tcagatgcag
     4141 ttggccagca aagagagtga tattgagcaa ttgcgtgcta aacttttgga cctctcggat
     4201 tctacaagtg ttgctagttt tcctagtgct gatgaaactg atggtaacct cccagagtca
     4261 agaattgaag gttggctttc agtaccaaat agaggaaata tcaaacgata tggctggaag
     4321 aaacagtatg ttgtggtaag cagcaaaaaa attttgttct ataatgacga acaagataag
     4381 gagcaatcca atccatctat ggtattggac atagataaac tgtttcacgt tagacctgta
     4441 acccaaggag atgtgtatag agctgaaact gaagaaattc ctaaaatatt ccagatacta
     4501 tatgcaaatg aaggtgaatg tagaaaagat gtagagatgg aaccagtaca acaagctgaa
     4561 aaaactaatt tccaaaatca caaaggccat gagtttattc ctacactcta ccactttcct
     4621 gccaattgtg atgcctgtgc caaacctctc tggcatgttt ttaagccacc ccctgcccta
     4681 gagtgtcgaa gatgccatgt taagtgccac agagatcact tagataagaa agaggactta
     4741 atttgtccat gtaaagtaag ttatgatgta acatcagcaa gagatatgct gctgttagca
     4801 tgttctcagg atgaacaaaa aaaatgggta actcatttag taaagaaaat ccctaagaat
     4861 ccaccatctg gttttgttcg tgcttcccct cgaacgcttt ctacaagatc cactgcaaat
     4921 cagtctttcc ggaaagtggt caaaaataca tctggaaaaa ctagttaacc atgtgactga
     4981 gtgccctgtg gaatcgtgtg ggatgctacc tgataaacca ggcttcttta accatgcaga
     5041 gcagacaggc tgtttctttg acacaaatat cacaggcttc agggttaaga ttgctgtttt
     5101 tctgtccttg ctttggcaca acacactgag ggtttttttt attgcgggtt tgcctacagg
     5161 tagattagat taattattac tatgtaatgc aagtacagtt gggggaaagc ttaggtagat
     5221 atattttttt taaaaggtgc tgcctttttg gatttataag aaaatgcctg tcagtcgtga
     5281 tagaacagag ttttcctcat atgagtaaga ggaagggact ttcactttca agtggaacag
     5341 ccatcactat caagatcagc tcatggaagg agtaaagaaa atatctcaaa atgagacaaa
     5401 ctgaagtttt gttttttttt taatgactta agtttttgtg ctcttgcaag actatacaaa
     5461 actattttaa gaaagcagtg atatcacttg aacttcagtg ccctcactgt agaatttaaa
     5521 agccttactg ttgattgccc atgttggact tgatggagaa attaaatatc tttcattatg
     5581 ctttacaaaa tactgtatat gtttcagcaa gtttggggaa tgggagagga caaaaaaaag
     5641 ttacatttaa tctatgcatt tttgccaagc catattgagt tattttacta ctagagacat
     5701 taggaaacta actgtacaaa agaaccaagt ttaaaagcat tttgtggggt acatcatttc
     5761 tataattgta taatgtattt ctttgtggtt ttaaatgata aagacattaa gttaacaaac
     5821 atataagaaa tgtatgcact gtttgaaatg taaattattc ttagaacact ttcaatgggg
     5881 gttgcattgt ccttttagtg ccttaatttg agataattat tttactgcca tgagtaagta
     5941 tagaaatttc aaaaaatgta ttttcaaaaa attatgtgtg tcagtgagtt tttcattgat
     6001 aattggttta atttaaaata tttagaggtt tgttggactt tcataaattg agtacaatct
     6061 ttgcatcaaa ctacctgcta caataatgac tttataaaac tgcaaaaaat gtagaaggtt
     6121 gcaccaacat aaaaaggaaa tatggcaata catccatgat gttttccagt taacatagga
     6181 attaccagat aaatactgtt aaactcttgt ccagtaacaa gagttgattc atatggacag
     6241 tatgatttat tgtttatttt tttaaccaaa tacctcctca gtaatttata atggctttgc
     6301 agtaatgtgt atcagataag aagcactgga aaaccgatcg tctctaggat gatatgcatg
     6361 tttcaagtgg tattgaaagc cgcactgatg gatatgtaat aataaacata tctgttatta
     6421 atatactaat gactctgtgc tcatttaatg agaaataaaa gtaatttatg gatgggtatc
     6481 tttaattttt actgcaatgt gttttctcat ggctgaaatg aatggaaaac atacttcaaa
     6541 ttagtctctg attgtatata aatgtttgtg aaattccatg gttagattaa agtgtatttt
     6601 taaaagataa aacgtggtct tgggctctaa aacaagagtg ggaatagttc acatgaaaag
     6661 ctggctaaag tgtgttggaa aacaattctc catgggtctc ttgcatttct acacatcagg
     6721 gaagcagagg ctctgacaac ctttcttttg actatctttt ccaaggatat ttatgtagta
     6781 aacagccttg gaagatagag ttctcccttg tgaggatgtc gggttctttt actgtccagt
     6841 ataataaaga taacgtctcc cacctatgat gcaaacccac tgtgtgctca gcacccacct
     6901 gggccactct gcattgccca catggggctt ggagggcaaa gggaactgat ggaacgtgaa
     6961 acttatgctg cttttgctgt gctgtgaatg aagtcatctg actctgaccc aggggtctca
     7021 tctcttttgt caggatccat gaaactgtga ctggcagcat gcaaacagga taaaatctca
     7081 gcacagttcc tgacggtgtc cttactacct tctcagactc atcaccatta cctaatattt
     7141 taaggtccag ttgcagagaa cagagttaat tctaattagt ttaagcaaga gaagactttc
     7201 caaatgacat actaatctga acttagaatt gttgagaact gagagagctt tgaggaatca
     7261 ctcccaatgc cacattacag aactgggtca accaggagag ctgcttcctc ttctaagttc
     7321 aggaaaccac tcactcccaa gtataccaat attgagaggg tccagatagt gccataatca
     7381 ggaatccaca ctaccactgc tggttctctg caacacttgt caggcttgct acaatctacc
     7441 tccagttaga tgttttgtac cattcctctt gccacttaag aacctcatgt ctgcacactg
     7501 cctcagaaaa ggcacttcca tgaccctgct tgctggcatt tagcacagcc tgcatctcac
     7561 gtctgccttc tctaggtgca tctacgtggc caaaattaaa tcacatccag acccctagct
     7621 gcaagaaagt ctgagaaata tagcctctag ctttctctct aatttgttac aggaggacac
     7681 actaggagtg tggaatgaag gttcagcatt gagttagccc atgcacccac acctgtaagc
     7741 ttctctgaga tcaggaactc cagctttggg caacaaagaa aacatagcca ctgtcattat
     7801 tcacaggttc actcatgacc tgtcatttgg ggtttcagct taaattaacc cattcaccct
     7861 tcatttaaag taaaaaaaat aagtaaaaga acttaaatga caaactcata gttacttgag
     7921 tttgtaattc atagttaact ttcacagttc tataatcaat ctggaattca gagtgaggta
     7981 gagatcaagc agtatttctc ccatatggat attcagttga tactgcagta ttcattgaaa
     8041 atacttcttt cctgcatcgt aattcaggtg aacaatccat tggtgttatt tctgtgtcct
     8101 tgccaatatc acacttttaa ttactgtaac tttataataa gattttatat ctgtagtaga
     8161 agtccaactt tgtaatccct cccaattggc ttggctattc ttggcctttt gcatttccat
     8221 ataatttttt atttttgttt tgaaacgaag tttcgctctt gttgcccagg ctggagtgca
     8281 gtggcgcgat ctcggctcac tgcaacctcc gcctcccagg ttcaagtgat cctcctgcct
     8341 cagactcccg agtagctggg attacaggtg cccaccacca tgcccagcta atttttgtat
     8401 ttttagtaga gacagggttt caccatgttg gccagcctgg tcttgaactc ctgacctcag
     8461 gtgatccaca cccaccttgg cctcccaaag tgctgggatt acaggcatga gccaccgcgc
     8521 ctggttgcat tcccatataa atttaaaaac aatctactga aagatgtata cgacctccac
     8581 caagaaaatt gtaagacatt tggagaagtt taaaaagaca tgaataaacg gaaatggttt
     8641 ttttaaataa acaaatgatt tttaaagttg atcattaggt taataaatag tcatataatg
     8701 acaatccgat gagattatgt tgcccagggt ggtctctaac tcctagcctc aagcagtttt
     8761 actctctcat tacaggtgta ggccaccgtg cctggcctga cacttggaaa tcttaatcac
     8821 aattattctt tgtttttata atgtttactg ttcaaatcaa tttctggttg gatagtatgt
     8881 atatataaag ccatgctcaa tggcctagat atatttactg ccaaatcttt tatgctttta
     8941 gtgttttttt tctggacaag atctatgctt attgcaataa attaaatgca aagaatattc
     9001 tagtagaaag tcagtctgca cttcctaaac cccaccccac cccaccaatt ccttcataac
     9061 tgttattaac agttagctgt gttttctaat ggattatctc caaagtatat gtaactcaga
     9121 tttttgtgag gtaggaaaag aataacatta attccacttc acatattgaa agtctaacat
     9181 acaaagagat taaatatctc ctttcttttg ccaaatgtta atgaattgtc ttatgagaat
     9241 taagatatga tactttctcc caagctatac tgtttcccat aaagtatttg agatgttgga
     9301 gattcaaggg aaaaaatata aatgcttaga aataaagtgt ataatgcaaa gattgtgaat
     9361 aaagtgacac ttgtatgtta atcctataaa ttggtttctt gtaccatgta ggatggtttg
     9421 gctattaaat tgaattaagt ggttca
//
