LOCUS       NM_001378902            8451 bp    mRNA    linear   PRI 11-JUN-2024
DEFINITION  Homo sapiens ROS proto-oncogene 1, receptor tyrosine kinase (ROS1),
            transcript variant 3, mRNA.
ACCESSION   NM_001378902
VERSION     NM_001378902.1
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 8451)
  AUTHORS   Gong,L., Voon,D.C., Nakayama,J., Takahashi,C. and Kohno,S.
  TITLE     RB1 loss induces quiescent state through downregulation of RAS
            signaling in mammary epithelial cells
  JOURNAL   Cancer Sci 115 (5), 1576-1586 (2024)
   PUBMED   38468443
  REMARK    GeneRIF: RB1 loss induces quiescent state through downregulation of
            RAS signaling in mammary epithelial cells.
REFERENCE   2  (bases 1 to 8451)
  AUTHORS   Xu,X., Li,Y., Xu,R., Meng,Y., Li,Z., Zuo,D. and Wu,Y.
  TITLE     CD74-ROS1 L2026M mutant enhances autophagy through the MEK/ERK
            pathway to promote invasion, metastasis and crizotinib resistance
            in non-small cell lung cancer cells
  JOURNAL   FEBS J 291 (6), 1199-1219 (2024)
   PUBMED   38148635
  REMARK    GeneRIF: CD74-ROS1 L2026M mutant enhances autophagy through the
            MEK/ERK pathway to promote invasion, metastasis and crizotinib
            resistance in non-small cell lung cancer cells.
REFERENCE   3  (bases 1 to 8451)
  AUTHORS   Iyer,S.R., Nusser,K., Jones,K., Shinde,P., Keddy,C., Beach,C.Z.,
            Aguero,E., Force,J., Shinde,U. and Davare,M.A.
  TITLE     Discovery of oncogenic ROS1 missense mutations with sensitivity to
            tyrosine kinase inhibitors
  JOURNAL   EMBO Mol Med 15 (10), e17367 (2023)
   PUBMED   37587872
  REMARK    GeneRIF: Discovery of oncogenic ROS1 missense mutations with
            sensitivity to tyrosine kinase inhibitors.
REFERENCE   4  (bases 1 to 8451)
  AUTHORS   Glaser,M., Rasokat,A., Prang,D., Nogova,L., Wompner,C., Schmitz,J.,
            Bitter,E., Terjung,I., Eisert,A., Fischer,R., John,F., von
            Levetzow,C., Michels,S., Riedel,R., Ruge,L., Scharpenseel,H.,
            Siebolts,U., Merkelbach-Bruse,S., Buettner,R., Bragelmann,J.,
            Wolf,J. and Scheffler,M.
  TITLE     Clinicopathologic and molecular characteristics of small-scale
            ROS1-mutant non-small cell lung cancer (NSCLC) patients
  JOURNAL   Lung Cancer 184, 107344 (2023)
   PUBMED   37579577
  REMARK    GeneRIF: Clinicopathologic and molecular characteristics of
            small-scale ROS1-mutant non-small cell lung cancer (NSCLC)
            patients.
REFERENCE   5  (bases 1 to 8451)
  AUTHORS   Schoot,R.A., Orbach,D., Minard Colin,V., Alaggio,R., Di Carlo,D.,
            Corradini,N., Mercolini,F., Milano,G.M., van Noesel,M.M., Rome,A.,
            Dall'Igna,P., Pajtler,K., Sparber-Sauer,M., Ferrari,A. and
            Casanova,M.
  TITLE     Inflammatory Myofibroblastic Tumor With ROS1 Gene Fusions in
            Children and Young Adolescents
  JOURNAL   JCO Precis Oncol 7, e2300323 (2023)
   PUBMED   37856763
  REMARK    GeneRIF: Inflammatory Myofibroblastic Tumor With ROS1 Gene Fusions
            in Children and Young Adolescents.
REFERENCE   6  (bases 1 to 8451)
  AUTHORS   Galland,F., Stefanova,M., Lafage,M. and Birnbaum,D.
  TITLE     Localization of the 5' end of the MCF2 oncogene to human chromosome
            15q15----q23
  JOURNAL   Cytogenet Cell Genet 60 (2), 114-116 (1992)
   PUBMED   1611909
REFERENCE   7  (bases 1 to 8451)
  AUTHORS   Birchmeier,C., O'Neill,K., Riggs,M. and Wigler,M.
  TITLE     Characterization of ROS1 cDNA from a human glioblastoma cell line
  JOURNAL   Proc Natl Acad Sci U S A 87 (12), 4799-4803 (1990)
   PUBMED   2352949
REFERENCE   8  (bases 1 to 8451)
  AUTHORS   Sharma,S., Birchmeier,C., Nikawa,J., O'Neill,K., Rodgers,L. and
            Wigler,M.
  TITLE     Characterization of the ros1-gene products expressed in human
            glioblastoma cell lines
  JOURNAL   Oncogene Res 5 (2), 91-100 (1989)
   PUBMED   2691958
REFERENCE   9  (bases 1 to 8451)
  AUTHORS   Birchmeier,C., Sharma,S. and Wigler,M.
  TITLE     Expression and rearrangement of the ROS1 gene in human glioblastoma
            cells
  JOURNAL   Proc Natl Acad Sci U S A 84 (24), 9270-9274 (1987)
   PUBMED   2827175
REFERENCE   10 (bases 1 to 8451)
  AUTHORS   Matsushime,H., Wang,L.H. and Shibuya,M.
  TITLE     Human c-ros-1 gene homologous to the v-ros sequence of UR2 sarcoma
            virus encodes for a transmembrane receptorlike molecule
  JOURNAL   Mol Cell Biol 6 (8), 3000-3004 (1986)
   PUBMED   3023956
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL132671.20 and Z98880.1.
            
            Summary: This proto-oncogene, highly-expressed in a variety of
            tumor cell lines, belongs to the sevenless subfamily of tyrosine
            kinase insulin receptor genes. The protein encoded by this gene is
            a type I integral membrane protein with tyrosine kinase activity.
            The protein may function as a growth or differentiation factor
            receptor. [provided by RefSeq, Jul 2008].
            
            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##
            RNAseq introns :: mixed sample support SAMEA1968189, SAMEA1968540
                              [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            inferred exon combination :: based on alignments, homology
            MANE Ensembl match        :: ENST00000368507.8/ ENSP00000357493.3
            RefSeq Select criteria    :: based on manual assertion,
                                         conservation
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-409               AL132671.20        61693-62101
            410-454             AL132671.20        69129-69173
            455-514             AL132671.20        71318-71377
            515-541             AL132671.20        73090-73116
            542-602             AL132671.20        77993-78053
            603-751             AL132671.20        83207-83355
            752-890             AL132671.20        84358-84496
            891-1092            AL132671.20        90519-90720
            1093-1169           AL132671.20        91371-91447
            1170-1292           AL132671.20        92897-93019
            1293-1477           AL132671.20        93289-93473
            1478-1575           AL132671.20        94314-94411
            1576-2072           AL132671.20        97789-98285
            2073-2285           AL132671.20        99643-99855
            2286-2396           AL132671.20        100636-100746
            2397-2575           AL132671.20        101774-101952
            2576-2767           AL132671.20        104127-104318
            2768-2868           AL132671.20        108476-108576
            2869-3083           AL132671.20        121345-121559
            3084-3244           AL132671.20        121894-122054
            3245-3389           AL132671.20        122431-122575
            3390-3652           AL132671.20        124770-125032
            3653-3716           AL132671.20        127230-127293
            3717-3919           AL132671.20        127624-127826
            3920-4125           AL132671.20        129626-129831
            4126-4360           AL132671.20        130720-130954
            4361-4412           Z98880.1           1-52
            4413-4589           Z98880.1           3515-3691
            4590-4792           Z98880.1           12419-12621
            4793-4937           Z98880.1           14137-14281
            4938-5170           Z98880.1           15049-15281
            5171-5347           Z98880.1           15370-15546
            5348-5516           Z98880.1           19341-19509
            5517-5634           Z98880.1           27235-27352
            5635-5825           Z98880.1           30267-30457
            5826-5909           Z98880.1           32266-32349
            5910-6045           Z98880.1           35287-35422
            6046-6208           Z98880.1           36651-36813
            6209-6273           Z98880.1           38429-38493
            6274-6403           Z98880.1           39409-39538
            6404-6501           Z98880.1           45564-45661
            6502-6702           Z98880.1           46400-46600
            6703-6837           Z98880.1           47753-47887
            6838-7001           Z98880.1           55544-55707
            7002-8451           Z98880.1           67879-69328
FEATURES             Location/Qualifiers
     source          1..8451
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q22.1"
     gene            1..8451
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /note="ROS proto-oncogene 1, receptor tyrosine kinase"
                     /db_xref="GeneID:6098"
                     /db_xref="HGNC:HGNC:10261"
                     /db_xref="MIM:165020"
     exon            1..409
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     CDS             287..7312
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /EC_number="2.7.10.1"
                     /note="isoform 3 precursor is encoded by transcript
                     variant 3; v-ros avian UR2 sarcoma virus oncogene homolog
                     1; transmembrane tyrosine-specific protein kinase;
                     proto-oncogene tyrosine-protein kinase ROS; ROS
                     proto-oncogene 1, receptor tyrosine kinase; proto-oncogene
                     c-Ros-1; c-ros oncogene 1, receptor tyrosine kinase"
                     /codon_start=1
                     /product="proto-oncogene tyrosine-protein kinase ROS
                     isoform 3 precursor"
                     /protein_id="NP_001365831.1"
                     /db_xref="CCDS:CCDS93994.1"
                     /db_xref="GeneID:6098"
                     /db_xref="HGNC:HGNC:10261"
                     /db_xref="MIM:165020"
                     /translation="MKNIYCLIPKLVNFATLGCLWISVVQCTVLNSCLKSCVTNLGQQ
                     LDLGTPHNLSEPCIQGCHFWNSVDQKNCALKCNDTYATVCERESCEVGCSSAEGAYEE
                     EVLENADLPTAPFASSIGSHNMTLRWKSANFSGVKYIIQWKYAQLLGSWTYTKTVSRP
                     SYVVKPLHPFTEYIFRVVWIFTAQLQLYSPPSPSYRTHPHGVPETAPLIRNIESSSPD
                     TVEVSWDPPQFPGGPILGYNLRLISKNQKLDAGTQRTSFQFYSTLPNTIYRFSIAAVN
                     EVGEGPEAESSITTSSSAVQQEEQWLFLSRKTSLRKRSLKHLVDEAHCLRLDAIYHNI
                     TGISVDVHQQIVYFSEGTLIWAKKAANMSDVSDLRIFYRGSGLISSISIDWLYQRMYF
                     IMDELVCVCDLENCSNIEEITPPSISAPQKIVADSYNGYVFYLLRDGIYRADLPVPSG
                     RCAEAVRIVESCTLKDFAIKPQAKRIIYFNDTAQVFMSTFLDGSASHLILPRIPFADV
                     KSFACENNDFLVTDGKVIFQQDALSFNEFIVGCDLSHIEEFGFGNLVIFGSSSQLHPL
                     PGRPQELSVLFGSHQALVQWKPPALAIGASPSAWQNWTYEVKVSTQDPPEVTHIFLNI
                     SGTMLNVPELQSAMKYKVSVRASSPKRPGPWSEPSVGTTLVPASEPPFIMAVKEDGLW
                     SKPLNSFGPGEFLSSDIGNVSDMDWYNNSLYYSDTKGDVFVWLLNGTDISENYHLPSI
                     AGAGALAFEWLGHFLYWAGKTYVIQRQSVLTGHTDIVTHVKLLVNDMVVDSVGGYLYW
                     TTLYSVESTRLNGESSLVLQTQPWFSGKKVIALTLDLSDGLLYWLVQDSQCIHLYTAV
                     LRGQSTGDTTITEFAAWSTSEISQNALMYYSGRLFWINGFRIITTQEIGQKTSVSVLE
                     PARFNQFTIIQTSLKPLPGNFSFTPKVIPDSVQESSFRIEGNASSFQILWNGPPAVDW
                     GVVFYSVEFSAHSKFLASEQHSLPVFTVEGLEPYALFNLSVTPYTYWGKGPKTSLSLR
                     APETVPSAPENPRIFILPSGKCCNKNEVVVEFRWNKPKHENGVLTKFEIFYNISNQSI
                     TNKTCEDWIAVNVTPSVMSFQLEGMSPRCFIAFQVRAFTSKGPGPYADVVKSTTSEIN
                     PFPHLITLLGNKIVFLDMDQNQVVWTFSAERVISAVCYTADNEMGYYAEGDSLFLLHL
                     HNRSSSELFQDSLVFDITVITIDWISRHLYFALKESQNGMQVFDVDLEHKVKYPREVK
                     IHNRNSTIISFSVYPLLSRLYWTEVSNFGYQMFYYSIISHTLHRILQPTATNQQNKRN
                     QCSCNVTEFELSGAMAIDTSNLEKPLIYFAKAQEIWAMDLEGCQCWRVITVPAMLGKT
                     LVSLTVDGDLIYWIITAKDSTQIYQAKKGNGAIVSQVKALRSRHILAYSSVMQPFPDK
                     AFLSLASDTVEPTILNATNTSLTIRLPLAKTNLTWYGITSPTPTYLVYYAEVNDRKNS
                     SDLKYRILEFQDSIALIEDLQPFSTYMIQIAVKNYYSDPLEHLPPGKEIWGKTKNGVP
                     EAVQLINTTVRSDTSLIISWRESHKPNGPKESVRYQLAISHLALIPETPLRQSEFPNG
                     RLTLLVTRLSGGNIYVLKVLACHSEEMWCTESHPVTVEMFNTPEKPYSLVPENTSLQF
                     NWKAPLNVNLIRFWVELQKWKYNEFYHVKTSCSQGPAYVCNITNLQPYTSYNVRVVVV
                     YKTGENSTSLPESFKTKAGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRK
                     STSNNLQNQNLRWKMTFNGSCSSVCTWKSKNLKGIFQFRVVAANNLGFGEYSGISENI
                     ILVGDDFWIPETSFILTIIVGIFLVVTIPLTFVWHRRLKNQKSAKEGVTVLINEDKEL
                     AELRGLAAGVGLANACYAIHTLPTQEEIENLPAFPREKLTLRLLLGSGAFGEVYEGTA
                     VDILGVGSGEIKVAVKTLKKGSTDQEKIEFLKEAHLMSKFNHPNILKQLGVCLLNEPQ
                     YIILELMEGGDLLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDL
                     AARNCLVSVKDYTSPRIVKIGDFGLARDIYKNDYYRKRGEGLLPVRWMAPESLMDGIF
                     TTQSDVWSFGILIWEILTLGHQPYPAHSNLDVLNYVQTGGRLEPPRNCPDDLWNLMTQ
                     CWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKSRDEANNSGVINESFEGEDGDVICLN
                     SDDIMPVALMETKNREGLNYMVLATECGQGEEKSEGPLGSQESESCGLRKEEKEPHAD
                     KDFCQEKQVAYCPSGKPEGLNYACLTHSGYGDGSD"
     exon            410..454
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            455..514
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            515..541
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            542..602
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            603..751
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            752..890
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            891..1092
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            1093..1169
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            1170..1292
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            1293..1477
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            1478..1575
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            1576..2072
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            2073..2285
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            2286..2396
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            2397..2575
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            2576..2767
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            2768..2868
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            2869..3083
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            3084..3244
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            3245..3389
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            3390..3652
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            3653..3716
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            3717..3919
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            3920..4125
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            4126..4412
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            4413..4589
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            4590..4792
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            4793..4937
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            4938..5170
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            5171..5347
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            5348..5516
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            5517..5634
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            5635..5825
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            5826..5909
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            5910..6045
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            6046..6208
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            6209..6273
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            6274..6403
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            6404..6501
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            6502..6702
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            6703..6837
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            6838..7001
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     exon            7002..8451
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      8423..8428
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /note="hexamer: ATTAAA"
     regulatory      8429..8434
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /note="hexamer: TATAAA"
     polyA_site      8442
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
     polyA_site      8451
                     /gene="ROS1"
                     /gene_synonym="c-ros-1; MCF3; ROS"
                     /note="major polyA site"
ORIGIN      
        1 gcacttctaa gaactaacct ttagtcactg ggtgacttta tgggagtaaa aggaagctgt
       61 tatgaaatag ctcttatgga actgttacaa gctttcaagc attcaaaggt ctaaatgaaa
      121 aaggctaagt attatttcaa aaggcaagta tatcctaata tagcaaaaca aacaaagcaa
      181 aatccatcag ctactcctcc aattgaagtg atgaagccca aataattcat atagcaaaat
      241 ggagaaaatt agaccggcca tctaaaaatc tgccattggt gaagtgatga agaacattta
      301 ctgtcttatt ccgaagcttg tcaattttgc aactcttggc tgcctatgga tttctgtggt
      361 gcagtgtaca gttttaaata gctgcctaaa gtcgtgtgta actaatctgg gccagcagct
      421 tgaccttggc acaccacata atctgagtga accgtgtatc caaggatgtc acttttggaa
      481 ctctgtagat cagaaaaact gtgctttaaa gtgtaatgat acttatgcca ccgtttgtga
      541 gcgggagtcg tgtgaggttg gctgtagcag cgcggaaggt gcatatgaag aggaagtact
      601 ggaaaatgca gacctaccaa ctgctccctt tgcttcttcc attggaagcc acaatatgac
      661 attacgatgg aaatctgcaa acttctctgg agtaaaatac atcattcagt ggaaatatgc
      721 acaacttctg ggaagctgga cttatactaa gactgtgtcc agaccgtcct atgtggtcaa
      781 gcccctgcac cccttcactg agtacatttt ccgagtggtt tggatcttca cagcgcagct
      841 gcagctctac tcccctccaa gtcccagtta caggactcat cctcatggag ttcctgaaac
      901 tgcacctttg attaggaata ttgagagctc aagtcccgac actgtggaag tcagctggga
      961 tccacctcaa ttcccaggtg gacctatttt gggttataac ttaaggctga tcagcaaaaa
     1021 tcaaaaatta gatgcaggga cacagagaac cagtttccag ttttactcca ctttaccaaa
     1081 tactatctac aggttttcta ttgcagcagt aaatgaagtt ggtgagggtc cagaagcaga
     1141 atctagtatt accacttcat cttcagcagt tcaacaagag gaacagtggc tctttttatc
     1201 cagaaaaact tctctaagaa agagatcttt aaaacattta gtagatgaag cacattgcct
     1261 tcggttggat gctatatacc ataatattac aggaatatct gttgatgtcc accagcaaat
     1321 tgtttatttc tctgaaggaa ctctcatatg ggcgaagaag gctgccaaca tgtctgatgt
     1381 atctgacctg agaatttttt acagaggttc aggattaatt tcttctatct ccatagattg
     1441 gctttatcaa agaatgtatt tcatcatgga tgaactggta tgtgtctgtg atttagagaa
     1501 ctgctcaaac atcgaggaaa ttactccacc ctctattagt gcacctcaaa aaattgtggc
     1561 tgattcatac aatgggtatg tcttttacct cctgagagat ggcatttata gagcagacct
     1621 tcctgtacca tctggccggt gtgcagaagc tgtgcgtatt gtggagagtt gcacgttaaa
     1681 ggactttgca atcaagccac aagccaagcg aatcatttac ttcaatgaca ctgcccaagt
     1741 cttcatgtca acatttctgg atggctctgc ttcccatctc atcctacctc gcatcccctt
     1801 tgctgatgtg aaaagttttg cttgtgaaaa caatgacttt cttgtcacag atggcaaggt
     1861 cattttccaa caggatgctt tgtcttttaa tgaattcatc gtgggatgtg acctgagtca
     1921 catagaagaa tttgggtttg gtaacttggt catctttggc tcatcctccc agctgcaccc
     1981 tctgccaggc cgcccgcagg agctttcggt gctgtttggc tctcaccagg ctcttgttca
     2041 atggaagcct cctgcccttg ccataggagc cagcccttct gcctggcaga actggaccta
     2101 tgaggtgaaa gtatccaccc aagaccctcc tgaagtcact catattttct tgaacataag
     2161 tggaaccatg ctgaatgtac ctgagctgca gagtgctatg aaatacaagg tttctgtgag
     2221 agcaagttct ccaaagaggc caggcccctg gtcagagccc tcagtgggta ctaccctggt
     2281 gccagctagt gaaccaccat ttatcatggc tgtgaaagaa gatgggcttt ggagtaaacc
     2341 attaaatagc tttggcccag gagagttctt atcctctgat ataggaaatg tgtcagacat
     2401 ggattggtat aacaacagcc tctactacag tgacacgaaa ggcgacgttt ttgtgtggct
     2461 gctgaatggg acggatatct cagagaatta tcacctaccc agcattgcag gagcaggggc
     2521 tttagctttt gagtggctgg gtcactttct ctactgggct ggaaagacat atgtgataca
     2581 aaggcagtct gtgttgacgg gacacacaga cattgttacc cacgtgaagc tattggtgaa
     2641 tgacatggtg gtggattcag ttggtggata tctctactgg accacactct attcagtgga
     2701 aagcaccaga ctaaatgggg aaagttccct tgtactacag acacagcctt ggttttctgg
     2761 gaaaaaggta attgctctaa ctttagacct cagtgatggg ctcctgtatt ggttggttca
     2821 agacagtcaa tgtattcacc tgtacacagc tgttcttcgg ggacagagca ctggggatac
     2881 caccatcaca gaatttgcag cctggagtac ttctgaaatt tcccagaatg cactgatgta
     2941 ctatagtggt cggctgttct ggatcaatgg ctttaggatt atcacaactc aagaaatagg
     3001 tcagaaaacc agtgtctctg ttttggaacc agccagattt aatcagttca caattattca
     3061 gacatccctt aagcccctgc cagggaactt ttcctttacc cctaaggtta ttccagattc
     3121 tgttcaagag tcttcattta ggattgaagg aaatgcttca agttttcaaa tcctgtggaa
     3181 tggtccccct gcggtagact ggggtgtagt tttctacagt gtagaattta gtgctcattc
     3241 taagttcttg gctagtgaac aacactcttt acctgtattt actgtggaag gactggaacc
     3301 ttatgcctta tttaatcttt ctgtcactcc ttatacctac tggggaaagg gccccaaaac
     3361 atctctgtca cttcgagcac ctgaaacagt tccatcagca ccagagaacc ccagaatatt
     3421 tatattacca agtggaaaat gctgcaacaa gaatgaagtt gtggtggaat ttaggtggaa
     3481 caaacctaag catgaaaatg gggtgttaac aaaatttgaa attttctaca atatatccaa
     3541 tcaaagtatt acaaacaaaa catgtgaaga ctggattgct gtcaatgtca ctccctcagt
     3601 gatgtctttt caacttgaag gcatgagtcc cagatgcttt attgccttcc aggttagggc
     3661 ctttacatct aaggggccag gaccatatgc tgacgttgta aagtctacaa catcagaaat
     3721 caacccattt cctcacctca taactcttct tggtaacaag atagtttttt tagatatgga
     3781 tcaaaatcaa gttgtgtgga cgttttcagc agaaagagtt atcagtgccg tttgctacac
     3841 agctgataat gagatgggat attatgctga aggggactca ctctttcttc tgcacttgca
     3901 caatcgctct agctctgagc ttttccaaga ttcactggtt tttgatatca cagttattac
     3961 aattgactgg atttcaaggc acctctactt tgcactgaaa gaatcacaaa atggaatgca
     4021 agtatttgat gttgatcttg aacacaaggt gaaatatccc agagaggtga agattcacaa
     4081 taggaattca acaataattt ctttttctgt atatcctctt ttaagtcgct tgtattggac
     4141 agaagtttcc aattttggct accagatgtt ctactacagt attatcagtc acaccttgca
     4201 ccgaattctg caacccacag ctacaaacca acaaaacaaa aggaatcaat gttcttgtaa
     4261 tgtgactgaa tttgagttaa gtggagcaat ggctattgat acctctaacc tagagaaacc
     4321 attgatatac tttgccaaag cacaagagat ctgggcaatg gatctggaag gctgtcagtg
     4381 ttggagagtt atcacagtac ctgctatgct cggaaaaacc cttgttagct taactgtgga
     4441 tggagatctt atatactgga tcatcacagc aaaggacagc acacagattt atcaggcaaa
     4501 gaaaggaaat ggggccatcg tttcccaggt gaaggcccta aggagtaggc atatcttggc
     4561 ttacagttca gttatgcagc cttttccaga taaagcgttt ctgtctctag cttcagacac
     4621 tgtggaacca actatactta atgccactaa cactagcctc acaatcagat tacctctggc
     4681 caagacaaac ctcacatggt atggcatcac cagccctact ccaacatacc tggtttatta
     4741 tgcagaagtt aatgacagga aaaacagctc tgacttgaaa tatagaattc tggaatttca
     4801 ggacagtata gctcttattg aagatttaca accattttca acatacatga tacagatagc
     4861 tgtaaaaaat tattattcag atcctttgga acatttacca ccaggaaaag agatttgggg
     4921 aaaaactaaa aatggagtac cagaggcagt gcagctcatt aatacaactg tgcggtcaga
     4981 caccagcctc attatatctt ggagagaatc tcacaagcca aatggaccta aagaatcagt
     5041 ccgttatcag ttggcaatct cacacctggc cctaattcct gaaactcctc taagacaaag
     5101 tgaatttcca aatggaaggc tcactctcct tgttactaga ctgtctggtg gaaatattta
     5161 tgtgttaaag gttcttgcct gccactctga ggaaatgtgg tgtacagaga gtcatcctgt
     5221 cactgtggaa atgtttaaca caccagagaa accttattcc ttggttccag agaacactag
     5281 tttgcaattt aattggaagg ctccattgaa tgttaacctc atcagatttt gggttgagct
     5341 acagaagtgg aaatacaatg agttttacca tgttaaaact tcatgcagcc aaggtcctgc
     5401 ttatgtctgt aatatcacaa atctacaacc ttatacttca tataatgtca gagtagtggt
     5461 ggtttataag acgggagaaa atagcacctc acttccagaa agctttaaga caaaagctgg
     5521 agtcccaaat aaaccaggca ttcccaaatt actagaaggg agtaaaaatt caatacagtg
     5581 ggagaaagct gaagataatg gatgtagaat tacatactat atccttgaga taagaaagag
     5641 cacttcaaat aatttacaga accagaattt aaggtggaag atgacattta atggatcctg
     5701 cagtagtgtt tgcacatgga agtccaaaaa cctgaaagga atatttcagt tcagagtagt
     5761 agctgcaaat aatctagggt ttggtgaata tagtggaatc agtgagaata ttatattagt
     5821 tggagatgat ttttggatac cagaaacaag tttcatactt actattatag ttggaatatt
     5881 tctggttgtt acaatcccac tgacctttgt ctggcataga agattaaaga atcaaaaaag
     5941 tgccaaggaa ggggtgacag tgcttataaa cgaagacaaa gagttggctg agctgcgagg
     6001 tctggcagcc ggagtaggcc tggctaatgc ctgctatgca atacatactc ttccaaccca
     6061 agaggagatt gaaaatcttc ctgccttccc tcgggaaaaa ctgactctgc gtctcttgct
     6121 gggaagtgga gcctttggag aagtgtatga aggaacagca gtggacatct taggagttgg
     6181 aagtggagaa atcaaagtag cagtgaagac tttgaagaag ggttccacag accaggagaa
     6241 gattgaattc ctgaaggagg cacatctgat gagcaaattt aatcatccca acattctgaa
     6301 gcagcttgga gtttgtctgc tgaatgaacc ccaatacatt atcctggaac tgatggaggg
     6361 aggagacctt cttacttatt tgcgtaaagc ccggatggca acgttttatg gtcctttact
     6421 caccttggtt gaccttgtag acctgtgtgt agatatttca aaaggctgtg tctacttgga
     6481 acggatgcat ttcattcaca gggatctggc agctagaaat tgccttgttt ccgtgaaaga
     6541 ctataccagt ccacggatag tgaagattgg agactttgga ctcgccagag acatctataa
     6601 aaatgattac tatagaaaga gaggggaagg cctgctccca gttcggtgga tggctccaga
     6661 aagtttgatg gatggaatct tcactactca atctgatgta tggtcttttg gaattctgat
     6721 ttgggagatt ttaactcttg gtcatcagcc ttatccagct cattccaacc ttgatgtgtt
     6781 aaactatgtg caaacaggag ggagactgga gccaccaaga aattgtcctg atgatctgtg
     6841 gaatttaatg acccagtgct gggctcaaga acccgaccaa agacctactt ttcatagaat
     6901 tcaggaccaa cttcagttat tcagaaattt tttcttaaat agcatttata agtccagaga
     6961 tgaagcaaac aacagtggag tcataaatga aagctttgaa ggtgaagatg gcgatgtgat
     7021 ttgtttgaat tcagatgaca ttatgccagt tgctttaatg gaaacgaaga accgagaagg
     7081 gttaaactat atggtacttg ctacagaatg tggccaaggt gaagaaaagt ctgagggtcc
     7141 tctaggctcc caggaatctg aatcttgtgg tctgaggaaa gaagagaagg aaccacatgc
     7201 agacaaagat ttctgccaag aaaaacaagt ggcttactgc ccttctggca agcctgaagg
     7261 cctgaactat gcctgtctca ctcacagtgg atatggagat gggtctgatt aatagcgttg
     7321 tttgggaaat agagagttga gataaacact ctcattcagt agttactgaa agaaaactct
     7381 gctagaatga taaatgtcat ggtggtctat aactccaaat aaacaatgca acgttcctga
     7441 tttctaatct tggttctgag agccatttgg tttcagttgt agcaatcccc ataccagctg
     7501 cctgactttc agtagaatta tgagatgaac actaagcatg tggaaagctt aggaagactc
     7561 agaagtctgg aagggaaaca ctgctctccc ttctcccttg aggtgcttta ggctcttacc
     7621 cacctttcag tttgggctgt aataaaaata tcttggccac atgtttagag acagaatagg
     7681 tgtgttcagc gatataaaga agaggctaag gagtaggctc aggggggtca actgaactac
     7741 agataatctc aaatgggacc aaggaaatga gaaataattt cacacataca gaagaaacca
     7801 gcacctgtga cttgagaaat cacttggaaa gctgttactg caatgatata tatattatct
     7861 ttttttaatt tttttttttt ttttttgaga cgaagtcttg ctctgttgcc caggctggag
     7921 ttcaatggca cgatctcggc actgcaaact ccacctcctg ggttcaagca attctcgtgc
     7981 ctcagcctcc taagtagctg ggattacagg cgtgtgccac cacgcccggc taatttttgt
     8041 atttttagta gagatgaggt ttcaccatat tggccaggct ggtctagaac tcctgacctc
     8101 gggatccacc tgccttggcc tcccaaagtg ctggattaca ggtgtgagcc accatgccta
     8161 gccgatatat attgtcttta atcactactg taaaatattt tgtagttttg aggcttacaa
     8221 cagtagattc agtcatgttg aaaataagac tgtgaagatc ttttaagtcc tgaagttttg
     8281 cattctgtaa tcttcagttg tataaaatca ctctgacttg tgtgctatta tggaaattaa
     8341 ctagtataaa gattgctatt tgccatatct attttatgta taaaatactt aagattacat
     8401 tttgtatcaa attatgctta aaattaaata taaatgatta tacaatgtta a
//
