LOCUS       NM_001324418            9508 bp    mRNA    linear   PRI 23-APR-2024
DEFINITION  Homo sapiens ADAM metallopeptidase domain 22 (ADAM22), transcript
            variant 7, mRNA.
ACCESSION   NM_001324418
VERSION     NM_001324418.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 9508)
  AUTHORS   Xu,K., Jiang,P., Chen,Z., Gu,X. and Zhang,T.
  TITLE     ADAM22 acts as a novel predictive biomarker for unfavorable
            prognosis and facilitates metastasis via PI3K/AKT signaling pathway
            in nasopharyngeal carcinoma
  JOURNAL   Pathol Res Pract 256, 155264 (2024)
   PUBMED   38518731
  REMARK    GeneRIF: ADAM22 acts as a novel predictive biomarker for
            unfavorable prognosis and facilitates metastasis via PI3K/AKT
            signaling pathway in nasopharyngeal carcinoma.
REFERENCE   2  (bases 1 to 9508)
  AUTHORS   van der Knoop,M.M., Maroofian,R., Fukata,Y., van Ierland,Y.,
            Karimiani,E.G., Lehesjoki,A.E., Muona,M., Paetau,A., Miyazaki,Y.,
            Hirano,Y., Selim,L., de Franca,M., Fock,R.A., Beetz,C.,
            Ruivenkamp,C.A.L., Eaton,A.J., Morneau-Jacob,F.D., Sagi-Dain,L.,
            Shemer-Meiri,L., Peleg,A., Haddad-Halloun,J., Kamphuis,D.J.,
            Peeters-Scholte,C.M.P.C.D., Kurul,S.H., Horvath,R., Lochmuller,H.,
            Murphy,D., Waldmuller,S., Spranger,S., Overberg,D., Muir,A.M.,
            Rad,A., Vona,B., Abdulwahad,F., Maddirevula,S., Povolotskaya,I.S.,
            Voinova,V.Y., Gowda,V.K., Srinivasan,V.M., Alkuraya,F.S.,
            Mefford,H.C., Alfadhel,M., Haack,T.B., Striano,P., Severino,M.,
            Fukata,M., Hilhorst-Hofstee,Y. and Houlden,H.
  TITLE     Biallelic ADAM22 pathogenic variants cause progressive
            encephalopathy and infantile-onset refractory epilepsy
  JOURNAL   Brain 145 (7), 2301-2312 (2022)
   PUBMED   35373813
  REMARK    GeneRIF: Biallelic ADAM22 pathogenic variants cause progressive
            encephalopathy and infantile-onset refractory epilepsy.
REFERENCE   3  (bases 1 to 9508)
  AUTHORS   Charmsaz,S., Doherty,B., Cocchiglia,S., Vareslija,D., Marino,A.,
            Cosgrove,N., Marques,R., Priedigkeit,N., Purcell,S., Bane,F.,
            Bolger,J., Byrne,C., O'Halloran,P.J., Brett,F., Sheehan,K.,
            Brennan,K., Hopkins,A.M., Keelan,S., Jagust,P., Madden,S.,
            Martinelli,C., Battaglini,M., Oesterreich,S., Lee,A.V., Ciofani,G.,
            Hill,A.D.K. and Young,L.S.
  TITLE     ADAM22/LGI1 complex as a new actionable target for breast cancer
            brain metastasis
  JOURNAL   BMC Med 18 (1), 349 (2020)
   PUBMED   33208158
  REMARK    GeneRIF: ADAM22/LGI1 complex as a new actionable target for breast
            cancer brain metastasis.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 9508)
  AUTHORS   Lee,S.H., Kwon,N.S., Baek,K.J., Yun,H.Y. and Kim,D.S.
  TITLE     LGI3 is secreted and binds to ADAM22 via TRIF-dependent NF-kappaB
            pathway in response to LPS in human keratinocytes
  JOURNAL   Cytokine 126, 154872 (2020)
   PUBMED   31627033
  REMARK    GeneRIF: LGI3 is secreted and binds to ADAM22 via TRIF-dependent
            NF-kappaB pathway in response to LPS in human keratinocytes.
REFERENCE   5  (bases 1 to 9508)
  AUTHORS   Li,J., Lu,M., Jin,J., Lu,X., Xu,T. and Jin,S.
  TITLE     miR-449a Suppresses Tamoxifen Resistance in Human Breast Cancer
            Cells by Targeting ADAM22
  JOURNAL   Cell Physiol Biochem 50 (1), 136-149 (2018)
   PUBMED   30278449
  REMARK    GeneRIF: ADAM22 is critically involved in miR-449a-reduced
            tamoxifen resistance of estrogen receptor-positive breast cancer
            cells as a direct target of miR-449a.
REFERENCE   6  (bases 1 to 9508)
  AUTHORS   Hillman,R.T., Green,R.E. and Brenner,S.E.
  TITLE     An unappreciated role for RNA surveillance
  JOURNAL   Genome Biol 5 (2), R8 (2004)
   PUBMED   14759258
REFERENCE   7  (bases 1 to 9508)
  AUTHORS   Zhu,Pc., Sun,Y., Xu,R., Sang,Y., Zhao,J., Liu,G., Cai,L., Li,C. and
            Zhao,S.
  TITLE     The interaction between ADAM 22 and 14-3-3zeta: regulation of cell
            adhesion and spreading
  JOURNAL   Biochem Biophys Res Commun 301 (4), 991-999 (2003)
   PUBMED   12589811
  REMARK    GeneRIF: role for the 14-3-3zeta/ADAM 22 association in the
            regulation of cell adhesion and related signaling events
REFERENCE   8  (bases 1 to 9508)
  AUTHORS   Harada,T., Nishie,A., Torigoe,K., Ikezaki,K., Shono,T., Maehara,Y.,
            Kuwano,M. and Wada,M.
  TITLE     The specific expression of three novel splice variant forms of
            human metalloprotease-like disintegrin-like cysteine-rich protein 2
            gene inBrain tissues and gliomas
  JOURNAL   Jpn J Cancer Res 91 (10), 1001-1006 (2000)
   PUBMED   11050470
REFERENCE   9  (bases 1 to 9508)
  AUTHORS   Poindexter,K., Nelson,N., DuBose,R.F., Black,R.A. and Cerretti,D.P.
  TITLE     The identification of seven metalloproteinase-disintegrin (ADAM)
            genes from genomic libraries
  JOURNAL   Gene 237 (1), 61-70 (1999)
   PUBMED   10524237
REFERENCE   10 (bases 1 to 9508)
  AUTHORS   Sagane,K., Ohya,Y., Hasegawa,Y. and Tanaka,I.
  TITLE     Metalloproteinase-like, disintegrin-like, cysteine-rich proteins
            MDC2 and MDC3: novel human cellular disintegrins highly expressed
            in the brain
  JOURNAL   Biochem J 334 (Pt 1) (Pt 1), 93-98 (1998)
   PUBMED   9693107
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DR000609.1, AC005164.2,
            AC004992.2, AC005075.2 and R41888.1.
            
            On Jun 2, 2019 this sequence version replaced NM_001324418.1.
            
            Summary: This gene encodes a member of the ADAM (a disintegrin and
            metalloprotease domain) family. Members of this family are
            membrane-anchored proteins structurally related to snake venom
            disintegrins, and have been implicated in a variety of biological
            processes involving cell-cell and cell-matrix interactions,
            including fertilization, muscle development, and neurogenesis.
            Unlike other members of the ADAM protein family, the protein
            encoded by this gene lacks metalloprotease activity since it has no
            zinc-binding motif. This gene is highly expressed in the brain and
            may function as an integrin ligand in the brain. In mice, it has
            been shown to be essential for correct myelination in the
            peripheral nervous system. Alternative splicing results in several
            transcript variants.[provided by RefSeq, Dec 2010].
            
            Transcript Variant: This variant (7) encodes isoform 7. The encoded
            isoform (7) may undergo proteolytic processing.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660803.101525.1,
                                           SRR14372079.3001090.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2152719, SAMEA2154665
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000413139.2/ ENSP00000412085.2
            RefSeq Select criteria :: based on manual assertion, conservation
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-42                DR000609.1         117-158
            43-300              AC005164.2         56155-56412
            301-461             AC005164.2         56888-57048
            462-538             AC005164.2         100198-100274
            539-605             AC004992.2         74357-74423
            606-688             AC005075.2         14238-14320
            689-752             AC005075.2         20646-20709
            753-822             AC005075.2         22807-22876
            823-893             AC005075.2         31651-31721
            894-968             AC005075.2         34664-34738
            969-1040            AC005075.2         36450-36521
            1041-1207           AC005075.2         37331-37497
            1208-1292           AC005075.2         38929-39013
            1293-1383           AC005075.2         40391-40481
            1384-1435           AC005075.2         42042-42093
            1436-1535           AC005075.2         49088-49187
            1536-1607           AC005075.2         51187-51258
            1608-1700           AC005075.2         51477-51569
            1701-1781           AC005075.2         55039-55119
            1782-1832           AC005075.2         57043-57093
            1833-1896           AC005075.2         57319-57382
            1897-2002           AC005075.2         59283-59388
            2003-2122           AC005075.2         61949-62068
            2123-2291           AC005075.2         69074-69242
            2292-2406           AC005075.2         71894-72008
            2407-2497           AC005075.2         74199-74289
            2498-2515           AC005075.2         77606-77623
            2516-2710           AC005075.2         84997-85191
            2711-2811           AC005075.2         87567-87667
            2812-2878           AC005075.2         88020-88086
            2879-2965           AC005075.2         92677-92763
            2966-3089           AC005075.2         99178-99301
            3090-9427           AC005075.2         102533-108870
            9428-9508           R41888.1           11-91               c
FEATURES             Location/Qualifiers
     source          1..9508
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q21.12"
     gene            1..9508
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /note="ADAM metallopeptidase domain 22"
                     /db_xref="GeneID:53616"
                     /db_xref="HGNC:HGNC:201"
                     /db_xref="MIM:603709"
     exon            1..300
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     CDS             216..3110
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /note="isoform 7 precursor is encoded by transcript
                     variant 7; a disintegrin and metalloproteinase domain 22;
                     disintegrin and metalloproteinase domain-containing
                     protein 22; metalloproteinase-like, disintegrin-like, and
                     cysteine-rich protein 2; metalloproteinase-disintegrin
                     ADAM22-3"
                     /codon_start=1
                     /product="disintegrin and metalloproteinase
                     domain-containing protein 22 isoform 7 precursor"
                     /protein_id="NP_001311347.1"
                     /db_xref="CCDS:CCDS94137.1"
                     /db_xref="GeneID:53616"
                     /db_xref="HGNC:HGNC:201"
                     /db_xref="MIM:603709"
                     /translation="MQAAVAVSVPFLLLCVLGTCPPARCGQAGDASLMELEKRKENRF
                     VERQSIVPLRLIYRSGGEDESRHDALDTRVRGDLGGPQLTHVDQASFQVDAFGTSFIL
                     DVVLNHDLLSSEYIERHIEHGGKTVEVKGGEHCYYQGHIRGNPDSFVALSTCHGLHGM
                     FYDGNHTYLIEPEENDTTQEDFHFHSVYKSRLFEFSLDDLPSEFQQVNITPSKFILKP
                     RPKRSKRQLRRYPRNVEEETKYIELMIVNDHLMFKKHRLSVVHTNTYAKSVVNMADLI
                     YKDQLKTRIVLVAMETWATDNKFAISENPLITLREFMKYRRDFIKEKSDAVHLFSGSQ
                     FESSRSGAAYIGGICSLLKGGGVNEFGKTDLMAVTLAQSLAHNIGIISDKRKLASGEC
                     KCEDTWSGCIMGDTGYYLPKKFTQCNIEEYHDFLNSGGGACLFNKPSKLLDPPECGNG
                     FIETGEECDCGTPAECVLEGAECCKKCTLTQDSQCSDGLCCKKCKFQPMGTVCREAVN
                     DCDIRETCSGNSSQCAPNIHKMDGYSCDGVQGICFGGRCKTRDRQCKYIWGQKVTASD
                     KYCYEKLNIEGTEKGNCGKDKDTWIQCNKRDVLCGYLLCTNIGNIPRLGELDGEITST
                     LVVQQGRTLNCSGGHVKLEEDVDLGYVEDGTPCGPQMMCLEHRCLPVASFNFSTCLSS
                     KEGTICSGNGVCSNELKCVCNRHWIGSDCNTYFPHNDDAKTGITLSGNGVAGTNIIIG
                     IIAGTILVLALILGITAWGYKNYREQRQLPQGDYVKKPGDGDSFYSDIPPGVSTNSAS
                     SSKKRSAFLSHFQISTCSITHYSISQNISLFCSRSNGLSHSWSERIPDTKHISDICEN
                     GRPRSNSWQGNLGGNKKKIRGKRFRPRSNSTEYLNPWFKRDYNVAKWVEDVNKNTEGP
                     YFRTLSPAKSPSSSTGSIASSRKYPYPMPPLPDEDKKVNRQSARLWETSI"
     exon            301..461
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            462..538
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            539..605
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            606..688
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            689..752
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            753..822
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            823..893
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            894..968
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            969..1040
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1041..1207
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1208..1292
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1293..1383
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1384..1435
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1436..1535
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1536..1607
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1608..1700
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1701..1781
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1782..1832
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1833..1896
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            1897..2002
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            2003..2122
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            2123..2291
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            2292..2406
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            2407..2497
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            2498..2515
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            2516..2710
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            2711..2811
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            2812..2878
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            2879..2965
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            2966..3089
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     exon            3090..9508
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      9485..9490
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /note="hexamer: AATAAA"
     polyA_site      9508
                     /gene="ADAM22"
                     /gene_synonym="ADAM 22; DEE61; EIEE61; MDC2"
                     /note="major polyA site"
ORIGIN      
        1 actcgctcgc tccccccgcc agcggaagcg tccgcgaagc acaatgcagc actgagccgc
       61 ggtggaggtt gcagcgccac ggccgccgca gcaccggccg gggctgggtg gaggtggccg
      121 cggggacccc gggggcgcgg agcgagggaa acggactcgg cggcgccggc atgaggagct
      181 gagcgtctcg ggcgaggcgg gctgacggca gcaccatgca ggcggcagtg gctgtgtccg
      241 tgcccttctt gctgctctgt gtcctgggga cctgccctcc ggcgcgctgc ggccaggcag
      301 gagacgcctc attgatggag ctagagaaga ggaaggaaaa ccgcttcgtg gagcgccaga
      361 gcatcgtgcc actgcgcctc atctaccgct cgggcggcga agacgaaagt cggcacgacg
      421 cgctcgacac gcgggtgcgg ggcgacctcg gtggcccgca gttgactcat gttgaccaag
      481 caagcttcca ggttgatgcc tttggaacgt cattcattct cgatgtcgtg ctaaatcatg
      541 atttgctgtc ctctgaatac atagagagac acattgaaca tggaggcaag actgtggaag
      601 ttaaaggagg agagcactgt tactaccagg gccatatccg aggaaaccct gactcatttg
      661 ttgcattgtc aacatgccac ggacttcatg ggatgttcta tgacgggaac cacacatatc
      721 tcattgagcc agaagaaaat gacactactc aagaggattt ccattttcat tcagtttaca
      781 aatccagact gtttgaattt tccttggatg atcttccatc tgaatttcag caagtaaaca
      841 ttactccatc aaaatttatt ttgaagccaa gaccaaaaag gagtaaacgg cagcttcgtc
      901 gatatcctcg taatgtagaa gaagaaacca aatacattga actgatgatt gtgaatgatc
      961 accttatgtt taaaaaacat cggctttccg ttgtacatac caatacctat gcgaaatctg
     1021 tggtgaacat ggcagattta atatataaag accaacttaa gaccaggata gtattggttg
     1081 ctatggaaac ctgggcgact gacaacaagt ttgccatatc tgaaaatcca ttgatcaccc
     1141 tacgtgagtt tatgaaatac aggagggatt ttatcaaaga gaaaagtgat gcagttcacc
     1201 ttttttcggg aagtcaattt gagagtagcc ggagcggggc agcttatatt ggtgggattt
     1261 gctcgttgct gaaaggagga ggcgtgaatg aatttgggaa aactgattta atggctgtta
     1321 cacttgccca gtcattagcc cataatattg gtattatctc agacaaaaga aagttagcaa
     1381 gtggtgaatg taaatgcgag gacacgtggt ccgggtgcat aatgggagac actggctatt
     1441 atcttcctaa aaagttcacc cagtgtaata ttgaagagta tcatgacttc ctgaatagtg
     1501 gaggtggtgc ctgccttttc aacaaacctt ctaagcttct tgatcctcct gagtgtggca
     1561 atggcttcat tgaaactgga gaggagtgtg attgtggaac cccggccgaa tgtgtccttg
     1621 aaggagcaga gtgttgtaag aaatgcacct tgactcaaga ctctcaatgc agtgacggtc
     1681 tttgctgtaa aaagtgcaag tttcagccta tgggcactgt gtgccgagaa gcagtaaatg
     1741 attgtgatat tcgtgaaacg tgctcaggaa attcaagcca gtgtgcccct aatattcata
     1801 aaatggatgg atattcatgt gatggtgttc agggaatttg ctttggagga agatgcaaaa
     1861 ccagagatag acaatgcaaa tacatttggg ggcaaaaggt gacagcatca gacaaatatt
     1921 gctatgagaa actgaatatt gaagggacgg agaagggtaa ctgtgggaaa gacaaagaca
     1981 catggataca gtgcaacaaa cgggatgtgc tttgtggtta ccttttgtgt accaatattg
     2041 gcaatatccc aaggcttgga gaactcgatg gtgaaatcac atctacttta gttgtgcagc
     2101 aaggaagaac attaaactgc agtggtgggc atgttaagct tgaagaagat gtagatcttg
     2161 gctatgtgga agatgggaca ccttgtggtc cccaaatgat gtgcttagaa cacaggtgtc
     2221 ttcctgtggc ttctttcaac tttagtactt gcttgagcag taaagaaggc actatttgct
     2281 caggaaatgg agtttgcagt aatgagctga agtgtgtgtg taacagacac tggataggtt
     2341 ctgattgcaa cacttacttc cctcacaatg atgatgcaaa gactggtatc actctgtctg
     2401 gcaatggtgt tgctggcacc aatatcataa taggcataat tgctggcacc attttagtgc
     2461 tggccctcat attaggaata actgcgtggg gttataaaaa ctatcgagaa cagagacagt
     2521 taccccaggg agattatgta aaaaagcctg gagatggtga ctctttttat agcgacattc
     2581 ctcccggagt cagcacaaac tcagcatcta gttctaagaa gaggtctgct tttctgtcgc
     2641 attttcagat ttctacctgt tccatcacac attattccat tagtcagaac atttcattat
     2701 tttgcagcag gtcaaatggg ctctctcatt cttggagtga aaggattcca gacacaaaac
     2761 atatttcaga catctgtgaa aatgggcgac ctcgaagtaa ctcttggcaa ggtaacctgg
     2821 gaggcaacaa aaagaaaatc agaggcaaaa gatttagacc tcggtctaat tcaactgagt
     2881 atttaaaccc atggttcaaa agagactata atgtagctaa gtgggtagaa gatgtgaata
     2941 aaaacactga aggaccatac tttaggactt tatctcctgc caagtctcct tcttcatcaa
     3001 ctgggtctat tgcctccagc agaaaatacc cttacccaat gcctccactt cctgatgagg
     3061 acaagaaagt gaaccgacaa agtgccaggc tatgggagac atccatttaa gatcaactgt
     3121 ttacatgtga tacatcgaaa actgtttact tcaactttta tagaaaccca ggctcatgga
     3181 atcactgcaa atctatctgc tcttcagaca atacgaagac cctctgagat gctacagagg
     3241 agaggaagcg gagtttcaca tctggttacc attttctttt tgtcattggc ttaggattta
     3301 actaaccatg aaaagaacta ctgaaatatt acactataac atggaacaat aaaggtactg
     3361 gtatgttaat ggataatccg catgacagat aatatgtaga aatattcata aagttaactc
     3421 acatgaccca aatgtagcaa gtttcctaag gtacaatagt ggattcagaa cttgacgttc
     3481 tgaggcacat cctcactgta aacagtaatg ctatatgcat gaagcttctg tttattgttt
     3541 tccatattta aggaaacaac atcccataat agaaatgagc atgcagggct aaggcatata
     3601 ggatttttct gcaggacttt aaagctttga aaggccaata tcccataggc taactttaaa
     3661 catgtatttt tatttttgtt ttgtttttta cttttcatat ttatattagc atacaaggac
     3721 aattgtatat atgtaacatt tttaaaattt taaaaaaatg cagctgttac acacaagtgt
     3781 attttgccaa atgcctaaaa attccgtcac aatcacatca tcgtcatcca tccagtgatc
     3841 ttcaaagact ataagcaggt aatgtaaata tagtggtcaa tgctgtaaat gtgtctctcc
     3901 ataattcgta tttgtccaaa acatgtgata tccctttaac ctgtgcacag tctggaggca
     3961 gttttattga gtgagtagtt gagtgagaga acaaaatgcc cagcaaaact tctggcctcc
     4021 acagtttgct gatgcaggag cccactctgc tgccgatggg ctgctccctg gaaatcatct
     4081 atcccatccg tccatcccat ctcatcccag tgagccagcc cctcagcagt gtgtgctgct
     4141 gagattaagc aagtgcacca aagacacatg agacaacgta ctgccagtga gctggtagct
     4201 tctggtttgc caatactcta accctttgtg gcctgaagtt ttgttccttg gcaaaacttt
     4261 gtagtcaccc ttatctgtga aatgaatgac ttgttttaac aaaaacaact ttgacactgt
     4321 tgattaagaa tatttgtcat cactgggatg tgaatcccaa caagtcattc tgcactgact
     4381 ctgaagcaag atgacggaag attctactgt ttgagttgag cagcttcaac cattcataaa
     4441 gggttaagtt agatctaaac cacagagatg cagcatctgc gaagttacac taacagctgg
     4501 tgggggaaag aatctgatgc tttgaaacat atatttttaa tccataggaa aataagattc
     4561 tattttaaaa gacccttctt taaaaccaaa gtttgatagc tgttataatg gcagatctgt
     4621 cattccaaaa gaaagctagc taccctagtg aggctggaga ttgatgggct caatcacatg
     4681 gtctgctctg aagtatactt ctgatttcct catttgctgt gtgttcttaa gaggaatgga
     4741 atctgcagac aggttttcag atatactctc ttaaatttga tcctctccca tagtatccat
     4801 ggacaaaatc catatcatct tcatatgtaa tcaatttgat tacatatcat gcccaaactg
     4861 aagggccgag ttagaaggca gcattttata ctgtgtgttt atgtcttctg taatggacct
     4921 ctcttttgaa agtctttgaa atgtttggaa agcaatttaa tgatccaaaa ttacataatg
     4981 taaaacagca tttttcatga caggaaggga tgtgattgtt gatatgacca taaagcgatc
     5041 catcaggcca aggtttgggt gagtgttggg cagtgttgcc acatagctca agccaagaac
     5101 agaagggcag acagattgaa agatgtagca aataaagtga ctttttacca agatcactgt
     5161 aacgtgcact gaatgtttcc tggtactgag tgtacaaaag gctaatgcta taaggtttat
     5221 tttgactata aaagagttta tagatttgaa tataaggtgc ctcatgtaaa tatgcttcct
     5281 agttacaggt acacaaactc taatttgaaa gaatccacaa atggctagct gagaagttaa
     5341 cagatctcta tcattcgtct gtgtgtcttt cttccctcac ctatttttac atgaaattat
     5401 tatttcaaat gaaaatcatg atcatgtgcc ttttgggaga catggtttct ctagaggtat
     5461 atagtttgta attacccgcc ttggtaataa ccttcctgtg gaactgacta aaaatttttg
     5521 ttttatttgt agagattatg atttgaggta tacagtaact ttaatgttct attcttggaa
     5581 tctactctat ctcccatgtt taaacattct tagagccatt tgtgggattc attgacaaat
     5641 ttatagtctc aagggagagt ttcaagaagt atctatatgt atactcatgg ttggggttct
     5701 agaggcatta catctaaata tttatgactt ttcatccacc gaggtaggta gcattaaata
     5761 tacaagcaca gcattatttc tctttaaata tctattttgg agagaaactt tgaggccgta
     5821 tcacagttta tatcatgcaa ctaatattta tatttcccaa tccactacaa aatcattgct
     5881 aagcagaaga gagcagttat ttggccttta tgttccattg tatgcctttt tcccctcttc
     5941 cagttttatg cattgataag actacagatt ggcaccctgc tgcctgagaa gttccattta
     6001 tccatagtca ttgcagtgca gtaaaccctg atttaaagga acatttaagt ctctccagta
     6061 agtgtgaaca ggaaggcatg ggatagaaga gagtccttat ggagtggact ggccacatga
     6121 actgtcctcc agccactctt tatttagatg ggaagtggca tggtcctctg aacgctgcag
     6181 gctggaaatg atccccaggg cacatgcaat ctgtggaaag gaatacatcg gacagtgcaa
     6241 catggtgagg gctttcaatt tgctgtggtt gctgtatttt taacaagaca cccggagctt
     6301 cgattaggaa taacctatca ttagagttgt tcctttaaaa aatgttgatg aataaagcaa
     6361 atgtgggttt aaaatgccaa cttatttttc actttgatat tggtgcttta ttaagtgata
     6421 ccatagtttc tctctctttt ccctgttact ttaaaaagaa ttttaaaatt gtgtttgtat
     6481 ataaggtcag tctggcatag aatttctgaa agtaacatta ataggatttc taaagaagtt
     6541 gtcagaaaga caaaattgga tattctctgc actttcagag aaggactatt tatgtttgaa
     6601 tttcataaca ggcttacatt tcttttctat tgattccctt gcatatctac ataatttaat
     6661 cctgtctatt gtcccagatc tcttgtggct actttacctg ttaccttttt tgggattttg
     6721 ttctttatgt tttacagtta ccttcggacc agaagatata tggtattttt attcactttt
     6781 ttcagtgttt taaaataagg tttgttcatt tattcatttt atccattcat ttcctattgt
     6841 cgtatagttc taaccatata tatagtactt taaatatttt cttatgttat tatttaacac
     6901 aataataaat tcttatctaa agaaaagatt attttacttt attttactta aaggaaagag
     6961 aatttattgg caggatattg agtagcttgt agagtatatg gaaggggaga gccaagttag
     7021 gaactggcag gagcgaggag ggacaagaca gctgcctgca cagtctgata ggacacatct
     7081 ggctgctgcc actggatgcc cacatgggca gcgtgttgta aatatcaccc taccagttgg
     7141 taagttggca tgaattttcc atgaaacact tgactgccat ttgcagcatc atatctactt
     7201 tttatgcacc taattatatt tttcctttca cttttatgtt tttttctaaa actgccacct
     7261 aaataccttt ccactccgtt aaatgtatgg agtcaagata aatttctcat tcttgctcta
     7321 cagtttaaga tgtataagaa gtaaacactt ccgtggaata gggcttaatt tggggctcaa
     7381 atgttttgtt ttcctcctga gatgtttttg aatggataag actactctgg ttttggatgc
     7441 agcaactttt ctcctggcat ggaagaacta aggactttga taaacagttt cccattgata
     7501 gtataatata atgaggggcc cagtctgctc ttgtgaaaat tggctgagcg gcagcagccc
     7561 atcccagctg tgtgtgagta gccccgctgt taaaagtaca cctgctggga attgttggca
     7621 catgctcata gcatatgctc tgtgggggag gtgcttttaa ttccaagagg agcttttctc
     7681 ccacatctgc ggatgcagaa caaagatgca gcaggacttt agaaaacagg agtgtttcta
     7741 ctgacatttt attcattgct ttgttagtcc cgcaaatgga gcaacttctg gttgtttgta
     7801 agcagaaaaa caaaacattc aaaaccaaaa acctaattag tacttttgtc ctttatatcc
     7861 ctaggatgct ctagggagta gaggtggcag gcatctttat cttcacccac tggcacatta
     7921 gcagcttatg caacttagga agtcactggg agatgagtcc taaaagcctg aatttcagga
     7981 tggggaggag ataagaagca gagaactttg ggagaccatg gggcatttag tcctggcata
     8041 gacacagaat ggatattcac aggaagattc ctgaggccag atatgcagga gagcacacat
     8101 tgtcacaagg ggtgtggtgg gaagagaggt gctggatgcc taagacagac ttctgtgctt
     8161 ggcagattga ctgagtgttg actctgaata ctttgtggtc cagtccataa taggccagtc
     8221 actcctgcct gatgcatccc tgttgcactg ttcataaaac ctgtatcata tggggaagct
     8281 tcaaggctgg caggcttttc atcaagtaat catcattcca tgttcctacg tatccttgaa
     8341 atcaaaacca ggcaatatgt gtgtttttgg ttttgtttta caaaaaggca tacaatgaga
     8401 cgaattctta agataatgca catacagaat catcaataaa gtttcaaaga gtttatgaag
     8461 aaaaggtatt ttcctttctt gtaaaaaatg ttatatatat ataatattct gatctgcatt
     8521 caccttaggg cttagcctct tattttatga attttcaggc tgtgatttgt gttggatggc
     8581 taagctctaa aataatgcaa atagccccaa tctttaaata tagcggtgct aagttgaaca
     8641 agtaacacaa tacagaaaat gctgatatga atacttagta ataatacaaa agttcctgct
     8701 aaattatata tgtgtatcac tgcctgacta gaaaccccac ttttcttttc taatccagca
     8761 caaaatcaaa ctctgattct acaaccagtc tttttaaagg gcaaaaatga ctcaacacct
     8821 ttgttttgta tggaaaactt ttttttttac actaactgca aaactgcttt aaaaaaaggc
     8881 ttattcagga tagataagca tgtactcctt ttttaacttg ctggaagact tgcccctcca
     8941 aactagcacc cccaaaagac aacttctttc agaaacgggg tgttttacct aaacatagta
     9001 gcttacatgt tagccagcag taggtcggca ctagtgtttt ccacggttat cacctttgac
     9061 aggtgatgtg catctataga tagtggaagc caccccatga ggaggtgtta atagcagcat
     9121 ggtttcactt ttggtaatca ggtaatcatg tgtatatact tagattcgca ttattttaac
     9181 atttctctgc tactctgcac ttcaggttcg ttaagctatt ttaataatta ctggggttat
     9241 ggcaaacacc aatggaaatg tatatggcaa ctgctttcct gagcaagtgt gatttgtttt
     9301 atggctgttc aagttataaa attgttctta cattgtaggt aaacaaaatc ttgatgtttt
     9361 taaaggtcac tgtaacttaa ggttcaaatt tctggcacag ttttattagt attcacttcg
     9421 gaagctaata agataccatg gttttctatg ttactcccat tgtaacatta gtaaagtgac
     9481 tttcaataaa agatttatgt tattttga
//
