LOCUS       NM_005099               9777 bp    mRNA    linear   PRI 29-OCT-2024
DEFINITION  Homo sapiens ADAM metallopeptidase with thrombospondin type 1 motif
            4 (ADAMTS4), transcript variant 1, mRNA.
ACCESSION   NM_005099
VERSION     NM_005099.6
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 9777)
  AUTHORS   Zhai,W., Yang,W., Ge,J., Xiao,X., Wu,K., She,K., Zhou,Y., Kong,Y.,
            Wu,L., Luo,S. and Pu,X.
  TITLE     ADAMTS4 exacerbates lung cancer progression via regulating c-Myc
            protein stability and activating MAPK signaling pathway
  JOURNAL   Biol Direct 19 (1), 94 (2024)
   PUBMED   39415271
  REMARK    GeneRIF: ADAMTS4 exacerbates lung cancer progression via regulating
            c-Myc protein stability and activating MAPK signaling pathway.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 9777)
  AUTHORS   Fang,F., Wang,B., Lu,X., Wang,L., Chen,X., Wang,G. and Yang,Y.
  TITLE     miR-126a-5p inhibits H1N1-induced inflammation and matrix protease
            secretion in lung fibroblasts by targeting ADAMTS-4
  JOURNAL   Arch Virol 169 (8), 164 (2024)
   PUBMED   38990242
  REMARK    GeneRIF: miR-126a-5p inhibits H1N1-induced inflammation and matrix
            protease secretion in lung fibroblasts by targeting ADAMTS-4.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 9777)
  AUTHORS   Wirths,O., Lehnen,C., Fricke,M., Talucci,I., Klafki,H.W.,
            Morgado,B., Lehmann,S., Munch,C., Liepold,T., Wiltfang,J.,
            Rostagno,A., Ghiso,J., Maric,H.M., Jahn,O. and Weggen,S.
  TITLE     Amino-terminally elongated Abeta peptides are generated by the
            secreted metalloprotease ADAMTS4 and deposit in a subset of
            Alzheimer's disease brains
  JOURNAL   Neuropathol Appl Neurobiol 50 (3), e12991 (2024)
   PUBMED   38867123
  REMARK    GeneRIF: Amino-terminally elongated Abeta peptides are generated by
            the secreted metalloprotease ADAMTS4 and deposit in a subset of
            Alzheimer's disease brains.
REFERENCE   4  (bases 1 to 9777)
  AUTHORS   Dancevic,C.M. and McCulloch,D.R.
  TITLE     Current and emerging therapeutic strategies for preventing
            inflammation and aggrecanase-mediated cartilage destruction in
            arthritis
  JOURNAL   Arthritis Res Ther 16 (5), 429 (2014)
   PUBMED   25606593
  REMARK    Review article
REFERENCE   5  (bases 1 to 9777)
  AUTHORS   Wainwright,S.D., Bondeson,J., Caterson,B. and Hughes,C.E.
  TITLE     ADAMTS-4_v1 is a splice variant of ADAMTS-4 that is expressed as a
            protein in human synovium and cleaves aggrecan at the interglobular
            domain
  JOURNAL   Arthritis Rheum 65 (11), 2866-2875 (2013)
   PUBMED   23897278
  REMARK    GeneRIF: ADAMTS-4_v1 is expressed as a protein in vivo in human
            osteoarthritis synovium, functions as an aggrecanase, and cleaves
            other proteoglycan substrates.
REFERENCE   6  (bases 1 to 9777)
  AUTHORS   Wainwright,S.D., Bondeson,J. and Hughes,C.E.
  TITLE     An alternative spliced transcript of ADAMTS4 is present in human
            synovium from OA patients
  JOURNAL   Matrix Biol 25 (5), 317-320 (2006)
   PUBMED   16723216
  REMARK    GeneRIF: analysis of osteoarthritic synovium using primers designed
            to amplify across the exon 8/9 junction resulted in amplification
            of the expected product and a smaller product missing 161 bp from
            the 5' end of exon 9, the result of alternative splicing
REFERENCE   7  (bases 1 to 9777)
  AUTHORS   Hurskainen,T.L., Hirohata,S., Seldin,M.F. and Apte,S.S.
  TITLE     ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of
            zinc metalloproteases. General features and genomic distribution of
            the ADAM-TS family
  JOURNAL   J Biol Chem 274 (36), 25555-25563 (1999)
   PUBMED   10464288
REFERENCE   8  (bases 1 to 9777)
  AUTHORS   Abbaszade,I., Liu,R.Q., Yang,F., Rosenfeld,S.A., Ross,O.H.,
            Link,J.R., Ellis,D.M., Tortorella,M.D., Pratta,M.A., Hollis,J.M.,
            Wynn,R., Duke,J.L., George,H.J., Hillman,M.C. Jr., Murphy,K.,
            Wiswall,B.H., Copeland,R.A., Decicco,C.P., Bruckner,R., Nagase,H.,
            Itoh,Y., Newton,R.C., Magolda,R.L., Trzaskos,J.M., Burn,T.C. et al.
  TITLE     Cloning and characterization of ADAMTS11, an aggrecanase from the
            ADAMTS family
  JOURNAL   J Biol Chem 274 (33), 23443-23450 (1999)
   PUBMED   10438522
REFERENCE   9  (bases 1 to 9777)
  AUTHORS   Tortorella,M.D., Burn,T.C., Pratta,M.A., Abbaszade,I., Hollis,J.M.,
            Liu,R., Rosenfeld,S.A., Copeland,R.A., Decicco,C.P., Wynn,R.,
            Rockwell,A., Yang,F., Duke,J.L., Solomon,K., George,H.,
            Bruckner,R., Nagase,H., Itoh,Y., Ellis,D.M., Ross,H., Wiswall,B.H.,
            Murphy,K., Hillman,M.C. Jr., Hollis,G.F., Newton,R.C.,
            Magolda,R.L., Trzaskos,J.M. and Arner,E.C.
  TITLE     Purification and cloning of aggrecanase-1: a member of the ADAMTS
            family of proteins
  JOURNAL   Science 284 (5420), 1664-1666 (1999)
   PUBMED   10356395
REFERENCE   10 (bases 1 to 9777)
  AUTHORS   Tang,B.L. and Hong,W.
  TITLE     ADAMTS: a novel family of proteases with an ADAM protease domain
            and thrombospondin 1 repeats
  JOURNAL   FEBS Lett 445 (2-3), 223-225 (1999)
   PUBMED   10094461
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL590714.27, DA098917.1,
            AF148213.1, BC063293.1, AY358886.1, AB014588.1 and AA603151.1.
            
            On Nov 23, 2018 this sequence version replaced NM_005099.5.
            
            Summary: This gene encodes a member of the ADAMTS (a disintegrin
            and metalloproteinase with thrombospondin motifs) protein family.
            Members of this family share several distinct protein modules,
            including a propeptide region, a metalloproteinase domain, a
            disintegrin-like domain, and a thrombospondin type 1 (TS) motif.
            Individual members of this family differ in the number of
            C-terminal TS motifs, and some have unique C-terminal domains. The
            enzyme encoded by this gene lacks a C-terminal TS motif. The
            encoded preproprotein is proteolytically processed to generate the
            mature protease. This protease is responsible for the degradation
            of aggrecan, a major proteoglycan of cartilage, and brevican, a
            brain-specific extracellular matrix protein. The expression of this
            gene is upregulated in arthritic disease and this may contribute to
            disease progression through the degradation of aggrecan.
            Alternative splicing results in multiple transcript variants, at
            least one of which encodes an isoform that is proteolytically
            processed. [provided by RefSeq, Feb 2016].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the shorter isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803612.74836.1,
                                           SRR1660805.163035.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000367996.6/ ENSP00000356975.4
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1                 AL590714.27        54234-54234         c
            2-21                DA098917.1         28-47
            22-2303             AF148213.1         1-2282
            2304-3339           BC063293.1         2302-3337
            3340-3408           AY358886.1         3331-3399
            3409-3541           BC063293.1         3407-3539
            3542-3709           AB014588.1         3517-3684
            3710-4213           AF148213.1         3688-4191
            4214-4350           AA603151.1         28-164              c
            4351-9777           AL590714.27        39482-44908         c
FEATURES             Location/Qualifiers
     source          1..9777
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q23.3"
     gene            1..9777
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /note="ADAM metallopeptidase with thrombospondin type 1
                     motif 4"
                     /db_xref="GeneID:9507"
                     /db_xref="HGNC:HGNC:220"
                     /db_xref="MIM:603876"
     exon            1..1060
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /inference="alignment:Splign:2.1.0"
     CDS             428..2941
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /EC_number="3.4.24.82"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 1; aggrecanase-1; a disintegrin-like and
                     metalloprotease (reprolysin type) with thrombospondin type
                     1 motif, 4; a disintegrin and metalloproteinase with
                     thrombospondin motifs 4; ADAM-TS4; ADAM-TS 4; epididymis
                     secretory sperm binding protein"
                     /codon_start=1
                     /product="A disintegrin and metalloproteinase with
                     thrombospondin motifs 4 isoform 1 preproprotein"
                     /protein_id="NP_005090.3"
                     /db_xref="CCDS:CCDS1223.1"
                     /db_xref="GeneID:9507"
                     /db_xref="HGNC:HGNC:220"
                     /db_xref="MIM:603876"
                     /translation="MSQTGSHPGRGLAGRWLWGAQPCLLLPIVPLSWLVWLLLLLLAS
                     LLPSARLASPLPREEEIVFPEKLNGSVLPGSGAPARLLCRLQAFGETLLLELEQDSGV
                     QVEGLTVQYLGQAPELLGGAEPGTYLTGTINGDPESVASLHWDGGALLGVLQYRGAEL
                     HLQPLEGGTPNSAGGPGAHILRRKSPASGQGPMCNVKAPLGSPSPRPRRAKRFASLSR
                     FVETLVVADDKMAAFHGAGLKRYLLTVMAAAAKAFKHPSIRNPVSLVVTRLVILGSGE
                     EGPQVGPSAAQTLRSFCAWQRGLNTPEDSDPDHFDTAILFTRQDLCGVSTCDTLGMAD
                     VGTVCDPARSCAIVEDDGLQSAFTAAHELGHVFNMLHDNSKPCISLNGPLSTSRHVMA
                     PVMAHVDPEEPWSPCSARFITDFLDNGYGHCLLDKPEAPLHLPVTFPGKDYDADRQCQ
                     LTFGPDSRHCPQLPPPCAALWCSGHLNGHAMCQTKHSPWADGTPCGPAQACMGGRCLH
                     MDQLQDFNIPQAGGWGPWGPWGDCSRTCGGGVQFSSRDCTRPVPRNGGKYCEGRRTRF
                     RSCNTEDCPTGSALTFREEQCAAYNHRTDLFKSFPGPMDWVPRYTGVAPQDQCKLTCQ
                     AQALGYYYVLEPRVVDGTPCSPDSSSVCVQGRCIHAGCDRIIGSKKKFDKCMVCGGDG
                     SGCSKQSGSFRKFRYGYNNVVTIPAGATHILVRQQGNPGHRSIYLALKLPDGSYALNG
                     EYTLMPSPTDVVLPGAVSLRYSGATAASETLSGHGPLAQPLTLQVLVAGNPQDTRLRY
                     SFFVPRPTPSTPRPTPQDWLHRRAQILEILRRRPWAGRK"
     exon            1061..1384
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1385..1517
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1518..1688
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1689..1975
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1976..2162
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /inference="alignment:Splign:2.1.0"
     exon            2163..2338
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /inference="alignment:Splign:2.1.0"
     exon            2339..2514
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /inference="alignment:Splign:2.1.0"
     exon            2515..9777
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4308..4313
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /note="hexamer: AATAAA"
     polyA_site      4331
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /note="major polyA site"
     polyA_site      4354
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
     regulatory      5013..5018
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /note="hexamer: AATAAA"
     polyA_site      5035
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
     regulatory      6812..6817
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /note="hexamer: AATACA"
     regulatory      6821..6826
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /note="hexamer: AATATA"
     polyA_site      6836
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
     polyA_site      6841
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
     regulatory      9752..9757
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
                     /note="hexamer: AATAAA"
     polyA_site      9777
                     /gene="ADAMTS4"
                     /gene_synonym="ADAMTS-2; ADAMTS-4; ADMP-1"
ORIGIN      
        1 gggagaaccc acagggagac ccacagacac atatgcacga gagagacaga ggaggaaaga
       61 gacagagaca aaggcacagc ggaagaaggc agagacaggg caggcacaga agcggcccag
      121 acagagtcct acagagggag aggccagaga agctgcagaa gacacaggca gggagagaca
      181 aagatccagg aaaggagggc tcaggaggag agtttggaga agccagaccc ctgggcacct
      241 ctcccaagcc caaggactaa gttttctcca tttcctttaa cggtcctcag cccttctgaa
      301 aactttgcct ctgaccttgg caggagtcca agcccccagg ctacagagag gagctttcca
      361 aagctagggt gtggaggact tggtgcccta gacggcctca gtccctccca gctgcagtac
      421 cagtgccatg tcccagacag gctcgcatcc cgggaggggc ttggcagggc gctggctgtg
      481 gggagcccaa ccctgcctcc tgctccccat tgtgccgctc tcctggctgg tgtggctgct
      541 tctgctactg ctggcctctc tcctgccctc agcccggctg gccagccccc tcccccggga
      601 ggaggagatc gtgtttccag agaagctcaa cggcagcgtc ctgcctggct cgggcgcccc
      661 tgccaggctg ttgtgccgct tgcaggcctt tggggagacg ctgctactag agctggagca
      721 ggactccggt gtgcaggtcg aggggctgac agtgcagtac ctgggccagg cgcctgagct
      781 gctgggtgga gcagagcctg gcacctacct gactggcacc atcaatggag atccggagtc
      841 ggtggcatct ctgcactggg atgggggagc cctgttaggc gtgttacaat atcggggggc
      901 tgaactccac ctccagcccc tggagggagg cacccctaac tctgctgggg gacctggggc
      961 tcacatccta cgccggaaga gtcctgccag cggtcaaggt cccatgtgca acgtcaaggc
     1021 tcctcttgga agccccagcc ccagaccccg aagagccaag cgctttgctt cactgagtag
     1081 atttgtggag acactggtgg tggcagatga caagatggcc gcattccacg gtgcggggct
     1141 aaagcgctac ctgctaacag tgatggcagc agcagccaag gccttcaagc acccaagcat
     1201 ccgcaatcct gtcagcttgg tggtgactcg gctagtgatc ctggggtcag gcgaggaggg
     1261 gccccaagtg gggcccagtg ctgcccagac cctgcgcagc ttctgtgcct ggcagcgggg
     1321 cctcaacacc cctgaggact cggaccctga ccactttgac acagccattc tgtttacccg
     1381 tcaggacctg tgtggagtct ccacttgcga cacgctgggt atggctgatg tgggcaccgt
     1441 ctgtgacccg gctcggagct gtgccattgt ggaggatgat gggctccagt cagccttcac
     1501 tgctgctcat gaactgggtc atgtcttcaa catgctccat gacaactcca agccatgcat
     1561 cagtttgaat gggcctttga gcacctctcg ccatgtcatg gcccctgtga tggctcatgt
     1621 ggatcctgag gagccctggt ccccctgcag tgcccgcttc atcactgact tcctggacaa
     1681 tggctatggg cactgtctct tagacaaacc agaggctcca ttgcatctgc ctgtgacttt
     1741 ccctggcaag gactatgatg ctgaccgcca gtgccagctg accttcgggc ccgactcacg
     1801 ccattgtcca cagctgccgc cgccctgtgc tgccctctgg tgctctggcc acctcaatgg
     1861 ccatgccatg tgccagacca aacactcgcc ctgggccgat ggcacaccct gcgggcccgc
     1921 acaggcctgc atgggtggtc gctgcctcca catggaccag ctccaggact tcaatattcc
     1981 acaggctggt ggctggggtc cttggggacc atggggtgac tgctctcgga cctgtggggg
     2041 tggtgtccag ttctcctccc gagactgcac gaggcctgtc ccccggaatg gtggcaagta
     2101 ctgtgagggc cgccgtaccc gcttccgctc ctgcaacact gaggactgcc caactggctc
     2161 agccctgacc ttccgcgagg agcagtgtgc tgcctacaac caccgcaccg acctcttcaa
     2221 gagcttccca gggcccatgg actgggttcc tcgctacaca ggcgtggccc cccaggacca
     2281 gtgcaaactc acctgccagg cccaggcact gggctactac tatgtgctgg agccacgggt
     2341 ggtagatggg accccctgtt ccccggacag ctcctcggtc tgtgtccagg gccgatgcat
     2401 ccatgctggc tgtgatcgca tcattggctc caagaagaag tttgacaagt gcatggtgtg
     2461 cggaggggac ggttctggtt gcagcaagca gtcaggctcc ttcaggaaat tcaggtacgg
     2521 atacaacaat gtggtcacta tccccgcggg ggccacccac attcttgtcc ggcagcaggg
     2581 aaaccctggc caccggagca tctacttggc cctgaagctg ccagatggct cctatgccct
     2641 caatggtgaa tacacgctga tgccctcccc cacagatgtg gtactgcctg gggcagtcag
     2701 cttgcgctac agcggggcca ctgcagcctc agagacactg tcaggccatg ggccactggc
     2761 ccagcctttg acactgcaag tcctagtggc tggcaacccc caggacacac gcctccgata
     2821 cagcttcttc gtgccccggc cgaccccttc aacgccacgc cccactcccc aggactggct
     2881 gcaccgaaga gcacagattc tggagatcct tcggcggcgc ccctgggcgg gcaggaaata
     2941 acctcactat cccggctgcc ctttctgggc accggggcct cggacttagc tgggagaaag
     3001 agagagcttc tgttgctgcc tcatgctaag actcagtggg gaggggctgt gggcgtgaga
     3061 cctgcccctc ctctctgccc taatgcgcag gctggccctg ccctggtttc ctgccctggg
     3121 aggcagtgat gggttagtgg atggaagggg ctgacagaca gccctccatc taaactgccc
     3181 cctctgccct gcgggtcaca ggagggaggg ggaaggcagg gagggcctgg gccccagttg
     3241 tatttattta gtatttattc acttttattt agcaccaggg aaggggacaa ggactagggt
     3301 cctggggaac ctgacccctg acccctcata gccctcaccc tggggctagg aaatccaggg
     3361 tggtggtgat aggtataagt ggtgtgtgta tgcgtgtgtg tgtgtgtgaa aatgtgtgtg
     3421 tgcttatgta tgaggtacaa cctgttctgc tttcctcttc ctgaatttta ttttttggga
     3481 aaagaaaagt caagggtagg gtgggccttc agggagtgag ggattatctt tttttttttt
     3541 tctttctttc tttctttttt ttttttgaga cagaatctcg ctctgtcgcc caggctggag
     3601 tgcaatggca caatctcggc tcactgcatc ctccgcctcc cgggttcaag tgattctcat
     3661 gcctcagcct cctgagtagc tgggattaca ggctcctgcc accacgcccg gctaattttt
     3721 gttttgtttt gtttggagac agagtctcgc tattgtcacc agggctggaa tgatttcagc
     3781 tcactgcaac cttcgccacc tgggttccag caattctcct gcctcagcct cccgagtagc
     3841 tgagattata ggcacctacc accacgcccg gctaattttt gtatttttag tagagacggg
     3901 gtttcaccat gttggccagg ctggtctcga actcctgacc ttaggtgatc cactcgcctt
     3961 catctcccaa agtgctggga ttacaggcgt gagccaccgt gcctggccac gcccaactaa
     4021 tttttgtatt tttagtagag acagggtttc accatgttgg ccaggctgct cttgaactcc
     4081 tgacctcagg taatcgacct gcctcggcct cccaaagtgc tgggattaca ggtgtgagcc
     4141 accacgcccg gtacatattt tttaaattga attctactat ttatgtgatc cttttggagt
     4201 cagacagatg tggttgcatc ctaactccat gtctctgagc attagatttc tcatttgcca
     4261 ataataatac ctcccttaga agtttgttgt gaggattaaa taatgtaaat aaagaactag
     4321 cataacactc agcatctagt aagtgctcaa caaatagcag ctgctgttac ttactgttat
     4381 caaatttctg tccacatcca ctctccatat gcacttgaag gtggcaaaga tccacaacca
     4441 tggtgcctgc ctttatcctc agggtccgtt cctttggttg gcagacccct atcctgggtt
     4501 ctgagggacc aacagagaaa ggaaaattcc atccctcacc tctggaagtt cccaatcaca
     4561 ggaaggaaac atagtaagca cgtggctaca aatacaattg acaagaacat gaaggtgcag
     4621 gataacaaga acaaataaca agaacaactg catcaacaca aatgagtgct tagtaataag
     4681 ggtgatagtt gaggggtctg ggtttcacaa cagtagaaag agcactggag tgggagccag
     4741 cgggtctgga ttcaatttgg ggctcggcgt cttattagct gggtggtgtt gggtaagtca
     4801 ctgatgctga gccttagatt gctcatatgg gactaacagt atctactccc acagagttgt
     4861 tctgggaaca aatgctagaa tattttcaaa atagtaaagg ttatagtcat ggccatgtga
     4921 gaggttaccc ctatgactac ctgaagatgg aacggagtct ccagaatctg ccagtgtaaa
     4981 cccagcagaa tgcctagaag atgtgagatt agaataaaat ttcataaaac aaaaacaatc
     5041 gggcacggtg gctcatgcct gtaatcccag cactttggga ggccgaaatg ggcggatcac
     5101 gaggtcagga gattgagacc gaccatcctg gctaccacag tgaaaccccg tgtctactaa
     5161 aaatacaaaa tatatatata tatatatata tatattagcc gggcatggtg acaggtgcct
     5221 atagtcccag ctacttggga gactgaggca ggagaatgac ttgcacccgg gaggcagagc
     5281 ttacagtgag tcgagattgc gccactgcac tccagcctgg gagacagagt gagactcgtc
     5341 tcgatacaaa aacaaaaaca aaaacaggat atggtttggc aggaaatagg caagaaggca
     5401 aaaagaataa cctggaaaag gatctgaggt aagggagcca ggtgcctcaa aatggcagaa
     5461 tacctgatgc ctgaggagag ggagggaata aaacatctgc attttcccct ctgggcaagg
     5521 cgcctttgct tgagaaagaa ttttgggctg gatgagatgg ttcacacctg taatcccagt
     5581 actttggcag gaggattgct tgaggccagg aggttgggac caacctgggc aacatagaaa
     5641 gattccatct ctaccaaaaa aaaaaaagat tgaaaaatta gccgggcgtg gtggcacctg
     5701 tagtcccagc tacttgggag gctaaaatag gaggactgct tgagcccacg atttcgaggc
     5761 tatggtgagc tacaatcatg ccactatact ccagcctggg tgagagacca aaacaccaac
     5821 tcaaaaaaaa aaaaaaaaaa aaaaaaaggg ccaggcatgg tggctcacac ctgtaatctc
     5881 agcactttgg gaggctgagg ttcaaaacca gccaggccaa catggtgaaa ccccatctct
     5941 actaaaaaaa aaatacaaaa aattagccag gtgtggtggc aagcgcctat agtcccagct
     6001 actcatgagg ctgaggcagg aggatcgctt gaacctggga ggtggaggtt gcagtgagcc
     6061 gaaattgcgc cattgcactc cagtctgggc gatagagtga gactccatct caaaaaaaaa
     6121 aaaaaaaaaa aaaagaactt gggcagtcct ctatgtgtca tggatggaac agggatgggc
     6181 aagggtggta ggtagaccct gcaagaattt ggagttttga gaggcagacg caggactgct
     6241 agggattggg gaaggtactg gatgtggggt tgtgggagaa actataggta aagaagaccc
     6301 tgaggttgag gtggaagagt gaagaatggg ggaaccaaag gcacttcact ctgccatagc
     6361 agcccctagc tgggatgcca aatactgctt ggaatgtgaa gctgggacta tggggttgag
     6421 gcaggccatg gaggttgtag tggttatatg tgctatgctt actggatctg ggctttgcta
     6481 atcaagttct gtaccaggca gtgccttata cagcaccctg tactctacac cagccagcac
     6541 agcgcctgct tcctctgcag caatgagaaa agactgccca cactctcttc tctccagtaa
     6601 acacggttct ccctgctagg cttggccccc tggcccttcc tgtggtcctc ctactaacca
     6661 ggctgaagaa gatggagaca agacaatagt gatctttact cgtttcatct agtttgcaaa
     6721 atgagaccac agatagtatg tttatggacc ttgatactat gagttgatgg tacaatgagc
     6781 agagttctgt gataagtaga tgtaaggtac aaatacaaac aatatatacg actgtcctaa
     6841 aggggttcac actgcattct gggcagggga ggttgtatac tgctcccact ccaccttccc
     6901 cgcaaacaga agcaatggga cagtaaaagg gactagaaga taagagccta atgagccctg
     6961 aactgaatgg actatgaggg ttatggaggg ctaccttggg ctgggccctg gagaacaggt
     7021 catcatgata gcccttctca ctttccttta atgttcatgg agatacactt ttttttttga
     7081 gatagggtct ccctttgttg accaggcagg agtacagtgg tgtgatcttg gctcactgca
     7141 gccttgaact ctcaggctca agcaaccctc ccacctcaac ctcctgagta cctaggacta
     7201 caggcacgag ctaccacacc cagctaattt actttttttt ttggttgaga cgaggtctta
     7261 tcatattgcc caggctggtc ttgaactcct ggcctcaagg gatcttccca cctcgatctc
     7321 ccaaagtgtt gggatgacca gtgtgaacca ccatgcctgg ccttttcttt tgagacagtc
     7381 tcgctctgtg gctcaggttg gagtgcagtg gcaccatcat aacttactac agccttgaac
     7441 tcctgggctc gagtaatcct cccacctcag cctcctaagt agcttggact acaggtgtag
     7501 attcactttt aaatcacttt tctgcctgtt attttaagag aaagcccttc gctcaccaag
     7561 tagggttctc actggcataa gtaagttttt ctgaaaatga gactgagctt aggggccacc
     7621 tctgtgattg ggtaagtaag caggagctag agtgaaagag gggcagagag agctagctca
     7681 tcgaagagaa gtgatgggca tctcagccct caatcccagg caaggcctga cccttttctg
     7741 gaatggtctc tgccttacca cacctccaag acccagattg taggtaggct ttacctaata
     7801 ggagtccaac aagttcttgc tagggatggg attgtggggg ggcacatatc tccctgtaag
     7861 agccacagtg agctctgttt cccatctgcc tacttattgc cctcgtgggc ctgagctggg
     7921 gtgtagatat ataaggagga acagaaacag taataacagg aagtaaggag gcactgaaac
     7981 aattcaagta tctggtcctg gagatgaaaa gaggaaatgg aaaaagaaaa ggcattgaat
     8041 gacaagggat tagaaccctg tccctagaga agttcaagaa gagtttggac aaccatttta
     8101 tgagatggca agtgttgtgc atgagtatgt gtttgaggtg ggggaggaag ttgaagcaat
     8161 aagttgggcc aatttcctaa agtcccttct gcccctgaga ttctctgctt ctgtggttca
     8221 aacagaggaa atctggacat ttgtccagcc actatttttg taatggaggt gggacagcca
     8281 gggttcctgg agtgtgctgt ggaatcggca tttacacttc tcttccatct ctagtctcat
     8341 ttctgtaatc ttcatacagt attacagtat tttgttttct aaaataccag attggcagta
     8401 agtgacaaaa ctagcatctc attggtcagg gcttgtgggg gaggaaggga gaagaaagtg
     8461 gatttcaatg tattaacatt ttattggctg agaggatgtt tctgaaccaa ttgagtacct
     8521 tccccattga ctgttgctgg ggccaagcca aaatcattgg caccacgaga aaccagatga
     8581 cagctggagg aaaccacgag tgctaaaaat gctcagaaag aggggggtca gggaaggcgg
     8641 gggagcaaca acactgaaca acttccccag gcaggatctt acatggggac agacccaggg
     8701 tacttaagta gcattaggaa ggaaagggag gggaggaagt agattaagta tccctcacag
     8761 tcttggcaca acaaacaggc accatacacc cacaccaaca gtgacacatt gacataacac
     8821 acatccaact tcacagagac acactagcac attctctctt ttttttaaaa tttattttat
     8881 tattattata ctttaagttt tagggtacat gtgcacaatg tgcaggttag ttacatatgt
     8941 atacatgtgc catgctggtg tgctgcaccc attaactcat catttagcat taggtatatc
     9001 tcctaatgct atccctcccc cctccccccc tgcctttctt tttcttcttt tttttcttaa
     9061 gacagattct cattctgtca cccaggctag agtgcaatgg cgtgatctcg gctcactgca
     9121 acctccacct cccaggttca agtgattctc ctgcctcagc ctgccaagta gctgggatta
     9181 caggtatgca ccaccatgcc cagctaattt tttgtatttt tagtatagag acggggtttt
     9241 ccatgttgcc caggctggtc ttgaactccc gggctcaagt gatctgcctg cctcggcctc
     9301 ccaaagtgct gggattacag gtgtgagcca gggtgcctgg ccaacacatt ctgttgataa
     9361 tatagatgca aataagtagt agggagcgga aaatgtaaga attttcacct gaaaatggat
     9421 ctgaagagta aaagatatta attgacctaa tcgtgcattg agaattgact gtttatccca
     9481 tttatttgtt caataaataa gccaatgggt tgtaaacatt gtaaacattc cacagcatgt
     9541 ggaaaggaca tggatttttg gagtcaaatt gaatctaagc cttgctactt acttacctgt
     9601 aatgatgcaa ccttaattac ttgatctctg taaacctcag tttccttacc tacaaaacgt
     9661 ttgtactatt acctgcctta tagagaggtc cagacttaag aatatgatga tgtaaatgtt
     9721 tggcactgtg tctggctttt agtaagtggt caataaaggc cagttctcct ttcctta
//
