LOCUS       NM_030569               6716 bp    mRNA    linear   PRI 24-JUN-2024
DEFINITION  Homo sapiens inter-alpha-trypsin inhibitor heavy chain 5 (ITIH5),
            transcript variant 1, mRNA.
ACCESSION   NM_030569
VERSION     NM_030569.7
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 6716)
  AUTHORS   Kosinski,J., Sechi,A., Hain,J., Villwock,S., Ha,S.A., Hauschulz,M.,
            Rose,M., Steib,F., Ortiz-Bruchle,N., Heij,L., Maas,S.L., van der
            Vorst,E.P.C., Knoesel,T., Altendorf-Hofmann,A., Simon,R.,
            Sauter,G., Bednarsch,J., Jonigk,D. and Dahl,E.
  TITLE     ITIH5 as a multifaceted player in pancreatic cancer suppression,
            impairing tyrosine kinase signaling, cell adhesion and migration
  JOURNAL   Mol Oncol 18 (6), 1486-1509 (2024)
   PUBMED   38375974
  REMARK    GeneRIF: ITIH5 as a multifaceted player in pancreatic cancer
            suppression, impairing tyrosine kinase signaling, cell adhesion and
            migration.
REFERENCE   2  (bases 1 to 6716)
  AUTHORS   Liu,J., Cao,F., Li,X., Zhang,L., Liu,Z., Li,X., Lin,J. and Han,C.
  TITLE     ITIH5, a p53-responsive gene, inhibits the growth and metastasis of
            melanoma cells by downregulating the transcriptional activity of
            KLF4
  JOURNAL   Cell Death Dis 12 (5), 438 (2021)
   PUBMED   33935281
  REMARK    GeneRIF: ITIH5, a p53-responsive gene, inhibits the growth and
            metastasis of melanoma cells by downregulating the transcriptional
            activity of KLF4.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 6716)
  AUTHORS   Rose,M., Noetzel,E., Kistermann,J., Eschenbruch,J., Rushrush,S.,
            Gan,L., Knuchel,R., Gaisa,N.T. and Dahl,E.
  TITLE     The ECM Modulator ITIH5 Affects Cell Adhesion, Motility and
            Chemotherapeutic Response of Basal/Squamous-Like (BASQ) Bladder
            Cancer Cells
  JOURNAL   Cells 10 (5), 1038 (2021)
   PUBMED   33924987
  REMARK    GeneRIF: The ECM Modulator ITIH5 Affects Cell Adhesion, Motility
            and Chemotherapeutic Response of Basal/Squamous-Like (BASQ) Bladder
            Cancer Cells.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 6716)
  AUTHORS   Young,E.D., Manley,S.J., Beadnell,T.C., Shearin,A.E., Sasaki,K.,
            Zimmerman,R., Kauffman,E., Vivian,C.J., Parasuram,A., Iwakuma,T.,
            Grandgenett,P.M., Hollingsworth,M.A., O'Neil,M. and Welch,D.R.
  TITLE     Suppression of pancreatic cancer liver metastasis by
            secretion-deficient ITIH5
  JOURNAL   Br J Cancer 124 (1), 166-175 (2021)
   PUBMED   33024269
  REMARK    GeneRIF: Suppression of pancreatic cancer liver metastasis by
            secretion-deficient ITIH5.
REFERENCE   5  (bases 1 to 6716)
  AUTHORS   Huth,S., Huth,L., Marquardt,Y., Fietkau,K., Dahl,E., Esser,P.R.,
            Martin,S.F., Heise,R., Merk,H.F. and Baron,J.M.
  TITLE     Inter-alpha-Trypsin Inhibitor Heavy Chain 5 (ITIH5) Is a Natural
            Stabilizer of Hyaluronan That Modulates Biological Processes in the
            Skin
  JOURNAL   Skin Pharmacol Physiol 33 (4), 198-206 (2020)
   PUBMED   32799206
  REMARK    GeneRIF: Inter-alpha-Trypsin Inhibitor Heavy Chain 5 (ITIH5) Is a
            Natural Stabilizer of Hyaluronan That Modulates Biological
            Processes in the Skin.
REFERENCE   6  (bases 1 to 6716)
  AUTHORS   Veeck,J., Chorovicer,M., Naami,A., Breuer,E., Zafrakas,M.,
            Bektas,N., Durst,M., Kristiansen,G., Wild,P.J., Hartmann,A.,
            Knuechel,R. and Dahl,E.
  TITLE     The extracellular matrix protein ITIH5 is a novel prognostic marker
            in invasive node-negative breast cancer and its aberrant expression
            is caused by promoter hypermethylation
  JOURNAL   Oncogene 27 (6), 865-876 (2008)
   PUBMED   17653090
  REMARK    GeneRIF: Promoter methylation-mediated loss of ITIH5 expression is
            associated with unfavourable outcome in breast cancer patients.
REFERENCE   7  (bases 1 to 6716)
  AUTHORS   Hamm,A., Veeck,J., Bektas,N., Wild,P.J., Hartmann,A.,
            Heindrichs,U., Kristiansen,G., Werbowetski-Ogilvie,T., Del
            Maestro,R., Knuechel,R. and Dahl,E.
  TITLE     Frequent expression loss of Inter-alpha-trypsin inhibitor heavy
            chain (ITIH) genes in multiple human solid tumors: a systematic
            expression analysis
  JOURNAL   BMC Cancer 8, 25 (2008)
   PUBMED   18226209
  REMARK    Publication Status: Online-Only
REFERENCE   8  (bases 1 to 6716)
  AUTHORS   Grupe,A., Li,Y., Rowland,C., Nowotny,P., Hinrichs,A.L., Smemo,S.,
            Kauwe,J.S., Maxwell,T.J., Cherny,S., Doil,L., Tacey,K., van
            Luchene,R., Myers,A., Wavrant-De Vrieze,F., Kaleem,M.,
            Hollingworth,P., Jehu,L., Foy,C., Archer,N., Hamilton,G.,
            Holmans,P., Morris,C.M., Catanese,J., Sninsky,J., White,T.J.,
            Powell,J., Hardy,J., O'Donovan,M., Lovestone,S., Jones,L.,
            Morris,J.C., Thal,L., Owen,M., Williams,J. and Goate,A.
  TITLE     A scan of chromosome 10 identifies a novel locus showing strong
            association with late-onset Alzheimer disease
  JOURNAL   Am J Hum Genet 78 (1), 78-88 (2006)
   PUBMED   16385451
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   9  (bases 1 to 6716)
  AUTHORS   Himmelfarb,M., Klopocki,E., Grube,S., Staub,E., Klaman,I.,
            Hinzmann,B., Kristiansen,G., Rosenthal,A., Durst,M. and Dahl,E.
  TITLE     ITIH5, a novel member of the inter-alpha-trypsin inhibitor heavy
            chain family is downregulated in breast cancer
  JOURNAL   Cancer Lett 204 (1), 69-77 (2004)
   PUBMED   14744536
  REMARK    GeneRIF: expression is consistantly lost or strongly downregulated
            in invasive ductal carcinoma; proposed that loss of ITIH5
            expression may be involved in breast cancer development
REFERENCE   10 (bases 1 to 6716)
  AUTHORS   Clark,H.F., Gurney,A.L., Abaya,E., Baker,K., Baldwin,D., Brush,J.,
            Chen,J., Chow,B., Chui,C., Crowley,C., Currell,B., Deuel,B.,
            Dowd,P., Eaton,D., Foster,J., Grimaldi,C., Gu,Q., Hass,P.E.,
            Heldens,S., Huang,A., Kim,H.S., Klimowski,L., Jin,Y., Johnson,S.,
            Lee,J., Lewis,L., Liao,D., Mark,M., Robbie,E., Sanchez,C.,
            Schoenfeld,J., Seshagiri,S., Simmons,L., Singh,J., Smith,V.,
            Stinson,J., Vagts,A., Vandlen,R., Watanabe,C., Wieand,D., Woods,K.,
            Xie,M.H., Yansura,D., Yi,S., Yu,G., Yuan,J., Zhang,M., Zhang,Z.,
            Goddard,A., Wood,W.I., Godowski,P. and Gray,A.
  TITLE     The secreted protein discovery initiative (SPDI), a large-scale
            effort to identify novel human secreted and transmembrane proteins:
            a bioinformatics assessment
  JOURNAL   Genome Res 13 (10), 2265-2270 (2003)
   PUBMED   12975309
  REMARK    Erratum:[Genome Res. 2003 Dec;13(12):2759]
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA246953.1, AY238437.1,
            AL833203.1, KF570249.1, AL355374.14 and BQ183379.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_030569.6.
            
            Summary: This gene encodes a heavy chain component of one of the
            inter-alpha-trypsin inhibitor (ITI) family members. ITI proteins
            are involved in extracellular matrix stabilization and in the
            prevention of tumor metastasis. They are also structurally related
            plasma serine protease inhibitors and are composed of a light chain
            and varying numbers of heavy chains. This family member is thought
            to function as a tumor suppressor in breast and thyroid cancers.
            Alternative splicing results in multiple transcript variants.
            [provided by RefSeq, Aug 2011].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            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 :: SRR1803613.223954.1,
                                           SRR1803614.141239.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000397146.7/ ENSP00000380333.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-72                DA246953.1         33-104
            73-1781             AY238437.1         1-1709
            1782-2880           AL833203.1         1659-2757
            2881-3059           KF570249.1         231-409
            3060-6017           AL355374.14        24305-27262         c
            6018-6716           BQ183379.1         18-716              c
FEATURES             Location/Qualifiers
     source          1..6716
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10p14"
     gene            1..6716
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /note="inter-alpha-trypsin inhibitor heavy chain 5"
                     /db_xref="GeneID:80760"
                     /db_xref="HGNC:HGNC:21449"
                     /db_xref="MIM:609783"
     exon            1..164
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     CDS             75..2903
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; inter-alpha-trypsin inhibitor heavy chain H5;
                     inter-alpha (globulin) inhibitor H5; inter-alpha-trypsin
                     inhibitor heavy chain family member 5; ITI heavy chain H5"
                     /codon_start=1
                     /product="inter-alpha-trypsin inhibitor heavy chain H5
                     isoform 1 precursor"
                     /protein_id="NP_085046.5"
                     /db_xref="CCDS:CCDS31139.2"
                     /db_xref="GeneID:80760"
                     /db_xref="HGNC:HGNC:21449"
                     /db_xref="MIM:609783"
                     /translation="MLLLLGLCLGLSLCVGSQEEAQSWGHSSEQDGLRVPRQVRLLQR
                     LKTKPLMTEFSVKSTIISRYAFTTVSCRMLNRASEDQDIEFQMQIPAAAFITNFTMLI
                     GDKVYQGEITEREKKSGDRVKEKRNKTTEENGEKGTEIFRASAVIPSKDKAAFFLSYE
                     ELLQRRLGKYEHSISVRPQQLSGRLSVDVNILESAGIASLEVLPLHNSRQRGSGRGED
                     DSGPPPSTVINQNETFANIIFKPTVVQQARIAQNGILGDFIIRYDVNREQSIGDIQVL
                     NGYFVHYFAPKDLPPLPKNVVFVLDSSASMVGTKLRQTKDALFTILHDLRPQDRFSII
                     GFSNRIKVWKDHLISVTPDSIRDGKVYIHHMSPTGGTDINGALQRAIRLLNKYVAHSG
                     IGDRSVSLIVFLTDGKPTVGETHTLKILNNTREAARGQVCIFTIGIGNDVDFRLLEKL
                     SLENCGLTRRVHEEEDAGSQLIGFYDEIRTPLLSDIRIDYPPSSVVQATKTLFPNYFN
                     GSEIIIAGKLVDRKLDHLHVEVTASNSKKFIILKTDVPVRPQKAGKDVTGSPRPGGDG
                     EGDTNHIERLWSYLTTKELLSSWLQSDDEPEKERLRQRAQALAVSYRFLTPFTSMKLR
                     GPVPRMDGLEEAHGMSAAMGPEPVVQSVRGAGTQPGPLLKKPYQPRIKISKTSVDGDP
                     HFVVDFPLSRLTVCFNIDGQPGDILRLVSDHRDSGVTVNGELIGAPAPPNGHKKQRTY
                     LRTITILINKPERSYLEITPSRVILDGGDRLVLPCNQSVVVGSWGLEVSVSANANVTV
                     TIQGSIAFVILIHLYKKPAPFQRHHLGFYIANSEGLSSNCHGLLGQFLNQDARLTEDP
                     AGPSQNLTHPLLLQVGEGPEAVLTVKGHQVPVVWKQRKIYNGEEQIDCWFARNNAAKL
                     IDGEYKDYLASHPFDTGMTLGRGMSREL"
     exon            165..209
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            210..373
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            374..475
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            476..726
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            727..896
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            897..1013
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            1014..1182
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            1183..1492
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            1493..2052
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            2053..2106
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            2107..2223
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            2224..2601
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     exon            2602..6716
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3539..3544
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /note="hexamer: AAGAAA"
     polyA_site      3562
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /note="major polyA site"
     regulatory      6290..6295
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /note="hexamer: AATAAA"
     polyA_site      6313
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /note="major polyA site"
     regulatory      6691..6696
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
                     /note="hexamer: AATAAA"
     polyA_site      6716
                     /gene="ITIH5"
                     /gene_synonym="ITI-HC5; PP14776"
ORIGIN      
        1 gcagtggctg gagccctggg cgctgcaaag cgtgtcccgc cgggtccccg agcgtcccgc
       61 gccctcgccc cgccatgctc ctgctgctgg ggctgtgcct ggggctgtcc ctgtgtgtgg
      121 ggtcgcagga agaggcgcag agctggggcc actcttcgga gcaggatgga ctcagggtcc
      181 cgaggcaagt cagactgttg cagaggctga aaaccaaacc tttgatgaca gaattctcag
      241 tgaagtctac catcatttcc cgttatgcct tcactacggt ttcctgcaga atgctgaaca
      301 gagcttctga agaccaggac attgagttcc agatgcagat tccagctgca gctttcatca
      361 ccaacttcac tatgcttatt ggagacaagg tgtatcaggg cgaaattaca gagagagaaa
      421 agaagagtgg tgatagggta aaagagaaaa ggaataaaac cacagaagaa aatggagaga
      481 aggggactga aatattcaga gcttctgcag tgattcccag caaggacaaa gccgcctttt
      541 tcctgagtta tgaggagctt ctgcagaggc gcctgggcaa gtacgagcac agcatcagcg
      601 tgcggcccca gcagctgtcc gggaggctga gcgtggacgt gaatatcctg gagagcgcgg
      661 gcatcgcatc cctggaggtg ctgccgcttc acaacagcag gcagaggggc agtgggcgcg
      721 gggaagatga ttctgggcct cccccatcta ctgtcattaa ccaaaatgaa acatttgcca
      781 acataatttt taaacctact gtagtacaac aagccaggat tgcccagaat ggaattttgg
      841 gagactttat cattagatat gacgtcaata gagaacagag cattggggac atccaggttc
      901 taaatggcta ttttgtgcac tactttgctc ctaaagacct tcctccttta cccaagaatg
      961 tggtattcgt gcttgacagc agtgcttcta tggtgggaac caaactccgg cagaccaagg
     1021 atgccctctt cacaattctc catgacctcc gaccccagga ccgtttcagt atcattggat
     1081 tttccaaccg gatcaaagta tggaaggacc acttgatatc agtcactcca gacagcatca
     1141 gggatgggaa agtgtacatt caccatatgt cacccactgg aggcacagac atcaacgggg
     1201 ccctgcagag ggccatcagg ctcctcaaca agtacgtggc ccacagtggc attggagacc
     1261 ggagcgtgtc cctcatcgtc ttcctgacgg atgggaagcc cacggtcggg gagacgcaca
     1321 ccctcaagat cctcaacaac acccgagagg ccgcccgagg ccaagtctgc atcttcacca
     1381 ttggcatcgg caacgacgtg gacttcaggc tgctggagaa actgtcgctg gagaactgtg
     1441 gcctcacacg gcgcgtgcac gaggaggagg acgcaggctc gcagctcatc gggttctacg
     1501 atgaaatcag gaccccgctc ctctctgaca tccgcatcga ttatcccccc agctcagtgg
     1561 tgcaggccac caagaccctg ttccccaact acttcaacgg ctcggagatc atcattgcgg
     1621 ggaagctggt ggacaggaag ctggatcacc tgcacgtgga ggtcaccgcc agcaacagta
     1681 agaaattcat catcctgaag acagatgtgc ctgtgcggcc tcagaaggca gggaaagatg
     1741 tcacaggaag ccccaggcct ggaggcgatg gagaggggga caccaaccac atcgagcgtc
     1801 tctggagcta cctcaccaca aaggagctgc tgagctcctg gctgcaaagt gacgatgaac
     1861 cggagaagga gcggctgcgg cagcgggccc aggccctggc tgtgagctac cgcttcctca
     1921 ctcccttcac ctccatgaag ctgagggggc cggtcccacg catggatggc ctggaggagg
     1981 cccacggcat gtcggctgcc atgggacccg aaccggtggt gcagagcgtg cgaggagctg
     2041 gcacgcagcc aggacctttg ctcaagaagc cataccagcc aagaattaaa atctctaaaa
     2101 catcagtgga tggtgatccc cactttgttg tggatttccc cctgagcaga ctcaccgtgt
     2161 gcttcaacat tgatgggcag cccggggaca tcctcaggct ggtctctgat cacagggact
     2221 ctggtgtcac agtgaacgga gagttaattg gggcacccgc ccctccaaat ggccacaaga
     2281 aacagcgcac ttacttgcgc actatcacca tcctcatcaa caagccagag agatcttatc
     2341 tcgagatcac accgagcaga gtcatcttgg atggtgggga cagactggtg ctcccctgca
     2401 accagagtgt ggtggtgggg agctgggggc tggaggtgtc cgtgtctgcc aacgccaatg
     2461 tcaccgtcac catccagggc tccatagcct ttgtcatcct catccacctc tacaaaaagc
     2521 cggcgccctt ccagcgacac cacctgggtt tctacattgc caacagcgag ggcctttcca
     2581 gcaactgcca cggactgctg ggtcagttcc tgaatcagga tgccagactc acagaagacc
     2641 ctgcagggcc cagccagaac ctcactcacc ctctgctcct tcaggtggga gaggggcctg
     2701 aggccgtcct aacagtgaaa ggccaccaag tcccagtggt ctggaagcaa aggaagattt
     2761 acaacgggga agagcagata gactgctggt ttgccaggaa caatgccgcc aaactgattg
     2821 acggggagta caaggattac ctggcatccc atccatttga cacagggatg acacttggcc
     2881 ggggaatgtc cagggagctc tgaagctggc agccttaaag atgcaagtgc atgaaggaca
     2941 gtgatgtggg gaggccgtgg ggcagctctt ttcatggctt gtacacgcct cagctcctgg
     3001 caattagctg gactccatga cccacccctg gtgcagcata gatccgacgt ctgtctgggc
     3061 gaagggtagg ggtgggtagg ggcgggaagc ctgagtgcaa atgtcatttc cctctactgc
     3121 ctcttcctgc ctctccccac cctgcccaca tccacagagg ggagagaagg gtcatagcta
     3181 aatgcaacaa agtctgtatc ttgtcccaac ctgcttttct gttctgttag catatcataa
     3241 agtaagcctt tctggtgaag gaaggttgct atgaaacttt ttttcttggt ggaaatggac
     3301 aagtttaggc actctgcttt ttgccttaca ctaatgctta gaaagctgtc ttttcagtgg
     3361 tgttgcagcc cccagatgtg tggccaacct ctgctgcaaa ggaatctctt gctgagtcca
     3421 ggccaccaat caggcaaata gcccatacat ttgatcgttg taaaccatga agtcttttct
     3481 tgcaagacgt ttttcttctg ctgtggtatc ttgcccttaa aaattagttt tcattaaaaa
     3541 gaaatttgat tgaaaataga aacatctaca gctcagatac tgatctcttt ctaatgggct
     3601 ttgtaaacca cttgactttg ctaatggcta ttctccaatt tgttccaata agctaagggc
     3661 ttttcataca caggacaact ccatgtggtt gattttactg gcatgtcttg gtgacgaaga
     3721 gttggccaag tgaatgatgc atcttttact tggagctctc cagcctttgt catagttccc
     3781 agaccttttt tccttgtggt catccaggag gtgatcaatt acatgtgcac agtgctagga
     3841 cgggaggcag agccggctca gagcaggtcc accagcccac ctatagcagg aagcgtgtcg
     3901 gtgcttagga aatctaggac ttccagcttc cctcatgtca gatagaaaaa aagtcaggaa
     3961 accagctcgt ggacaggggc tttggttcca aaacttggac aaacctgatg ccttaaggaa
     4021 aaggttaaga tgagagggga cttccagagt caatgaacgt cacccttcag cggacggata
     4081 ccgggagcgc ttgggcgaaa cagcagagaa agaaagactg tggtcgggga agtggaatgc
     4141 ttcgatgcag gccagagttc aaggctctgg ggctggcctc acaagaggct tcttccacgg
     4201 ggcttgacac cagagcagcc cccgcgtgaa atgagaaggc atgcttagca ctgggaggaa
     4261 aagctgagtt aagaaaattc tttatcatgt ttgccttccc tggggaaaca ttcaggcagt
     4321 aaaatgacat ccacgtgttc ctgtcggacg cagcggcttc gggaacaagt tagcgctggg
     4381 ggactatctg ggctcgtctc tctctgcttc gtgaacccac cacaccaggg cctgtctgct
     4441 gtgctattta tttgccttcc gtcttcccaa cctcagctgc ctgtattcat gccagaggtg
     4501 caaaggctgc cagccagtgc tgctgacaga tgctttcaga ctgtagagct cagagaaagg
     4561 gagcggcagc tagaggtagc cagggagctg gccaggctcc ccggggcctt cctattatgt
     4621 aaatcccagc tggacagaca gccctggagc caggtggccc tgtcccctgt ggagcacttg
     4681 gagcagtgat ctgttgttcc aggtgtaagt ctcgacactg cagaaatgag gacgttatta
     4741 ggaaagacca gttcctactg cctgtgttgc tactttaaga gctgagaaaa acattccaat
     4801 gagctatcca tagctaactt gcttgctcag aaaaacataa gtaacaaagt tgagctttca
     4861 tttttaaaaa ttatatttta ctttagaaaa atatcacctt ttttcttcct cttctttacg
     4921 tgtagatctt tttttttttt ttcaaatggg gtcagtacct gaaagcccga aaccccatac
     4981 caagcttata gttaggacct ttgcatttga taaaaaaaaa atatagtatt ttctgttgtc
     5041 cagaaaatct tcccagatag ggaaactgag gcagagagtg ccgtggagtg gtttttgcca
     5101 agtcatacaa catacttaat gcagggctac actgaacctc cagaatcatt ttgtttgctt
     5161 tgaccctgtt tcaccatctg ggcaatcatt tattttcctt gagcatttat aaaccagggc
     5221 gagggttgtt ccaaaatgag taattgaatg agatgaagaa atatgtcata attagaggag
     5281 ataaatctcc ttgttatcac aatagttaat gtgtcatgat cactgactaa ctgggacctt
     5341 gaacaagtca gcatctctgc ctttcaaaat gaaggaacat tgttctctat cctcccctga
     5401 cccccgacgg ccccatgcta ggtgcaccat cttcctccat ttgacttttt aatgctttac
     5461 aacttcaggc taaagggagg ggatgttggg aggagaaacc atcacaagat tccctcggtg
     5521 ccacagctgt gctgaggagg ccggggactg ggaatcggag tgggcacctc tgtgtttctc
     5581 tagggagtaa cattcaacat ttaattgaat cgtgtgtcct gataggtgga ttaggaacag
     5641 gattcattcc tttaacttta acttttggct aaacgacatg ccttggattg agtgtatatg
     5701 tcttccccaa attcatatgt tgaagcttaa atcctgaatg tgatggttct tggaattggg
     5761 acctttggaa ggttattggg tcttgagggc agagccctca cgaatgggat taaggccctt
     5821 ataagaagag acatggggcc aggtgcagtg gctcacacct gtaatcccaa cattttggga
     5881 ggccgagaag ggtggatcat gaggtcagga gatggagacc atcctggcca acatggtgaa
     5941 acctcgtctc tactaaaaat acaaaaatta gctgggcgtg gtggtgcgtg cctgtagttc
     6001 cagctacttg ggaggctgag gcaggagaat cgcttgaacc aggcagtcgg aacttgtagt
     6061 gagccaagat cacgccactg cactccagct ggagtgacag agccaaactc cgtcaaaaaa
     6121 aaacaaaaca aaacaaaaaa aagacatggg agagatggtg tttttcctct ccaccacctg
     6181 gggatacgat gagaagatgg ccacctgcaa gccaggaaga cggccctcac cagacaccat
     6241 gtctgctggc accttgatct tggacctccc agcctccaga actgtgagaa ataaatgtgt
     6301 tttgtttaag ctactcaagt ctgtggtatt cttgttaagg cagcccaagc tgactaagac
     6361 accaaatcat tcaaaacgtt aattcttttt ctgttcttta agcttcccag aatgtacaca
     6421 aacaatgctg ttattaaaat ttaaaggact cttggaactg taggacatga tccagctaaa
     6481 ataaataaca aataacacag ctaagcaaat acttataaat gtagctttaa atatttattt
     6541 tagttttaaa taattagtgg ggtacgagac agttcacatt caagagacat tttacttaga
     6601 caaaaaattt ataagagaac gatgcataaa aacaaacaac atattggtct gtttattttt
     6661 ctaagggaaa atggaattgg agctgttgag aataaaactt gaagaatcta actgca
//
