LOCUS       NM_031483               6743 bp    mRNA    linear   PRI 24-SEP-2024
DEFINITION  Homo sapiens itchy E3 ubiquitin protein ligase (ITCH), transcript
            variant 2, mRNA.
ACCESSION   NM_031483
VERSION     NM_031483.7
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 6743)
  AUTHORS   Shen,S., Cai,D., Liang,H., Zeng,G., Liu,W., Yan,R., Yu,X.,
            Zhang,H., Liu,S., Li,W., Deng,R., Lu,X., Liu,Y., Sun,J. and Guo,H.
  TITLE     NEDD4 family ubiquitin ligase AIP4 interacts with Alix to enable
            HBV naked capsid egress in an Alix ubiquitination-independent
            manner
  JOURNAL   PLoS Pathog 20 (9), e1012485 (2024)
   PUBMED   39259704
  REMARK    GeneRIF: NEDD4 family ubiquitin ligase AIP4 interacts with Alix to
            enable HBV naked capsid egress in an Alix
            ubiquitination-independent manner.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 6743)
  AUTHORS   Gahlot,P., Kravic,B., Rota,G., van den Boom,J., Levantovsky,S.,
            Schulze,N., Maspero,E., Polo,S., Behrends,C. and Meyer,H.
  TITLE     Lysosomal damage sensing and lysophagy initiation by SPG20-ITCH
  JOURNAL   Mol Cell 84 (8), 1556-1569 (2024)
   PUBMED   38503285
  REMARK    GeneRIF: Lysosomal damage sensing and lysophagy initiation by
            SPG20-ITCH.
REFERENCE   3  (bases 1 to 6743)
  AUTHORS   Totland,M.Z., Knudsen,L.M., Rasmussen,N.L., Omori,Y., Sorensen,V.,
            Elster,V.C.W., Stenersen,J.M., Larsen,M., Jensen,C.L., Zickfeldt
            Lade,A.A., Bruusgaard,E., Basing,S., Kryeziu,K., Brech,A.,
            Aasen,T., Lothe,R.A. and Leithe,E.
  TITLE     The E3 ubiquitin ligase ITCH negatively regulates intercellular
            communication via gap junctions by targeting connexin43 for
            lysosomal degradation
  JOURNAL   Cell Mol Life Sci 81 (1), 171 (2024)
   PUBMED   38597989
  REMARK    GeneRIF: The E3 ubiquitin ligase ITCH negatively regulates
            intercellular communication via gap junctions by targeting
            connexin43 for lysosomal degradation.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 6743)
  AUTHORS   Wang,Y., Hollingsworth,L.R., Sangare,L.O., Paredes-Santos,T.C.,
            Krishnamurthy,S., Penn,B.H., Wu,H. and Saeij,J.P.J.
  TITLE     Host E3 ubiquitin ligase ITCH mediates Toxoplasma gondii effector
            GRA35-triggered NLRP1 inflammasome activation and cell-autonomous
            immunity
  JOURNAL   mBio 15 (3), e0330223 (2024)
   PUBMED   38376248
  REMARK    GeneRIF: Host E3 ubiquitin ligase ITCH mediates Toxoplasma gondii
            effector GRA35-triggered NLRP1 inflammasome activation and
            cell-autonomous immunity.
REFERENCE   5  (bases 1 to 6743)
  AUTHORS   Lohr,N.J., Molleston,J.P., Strauss,K.A., Torres-Martinez,W.,
            Sherman,E.A., Squires,R.H., Rider,N.L., Chikwava,K.R.,
            Cummings,O.W., Morton,D.H. and Puffenberger,E.G.
  TITLE     Human ITCH E3 ubiquitin ligase deficiency causes syndromic
            multisystem autoimmune disease
  JOURNAL   Am J Hum Genet 86 (3), 447-453 (2010)
   PUBMED   20170897
  REMARK    GeneRIF: describe, in ten patients, identification of a mutation
            resulting in truncation of ITCH. These patients not only have
            multisystem autoimmune disease but also display morphologic and
            developmental abnormalities.
REFERENCE   6  (bases 1 to 6743)
  AUTHORS   Chen,X., Wen,S., Fukuda,M.N., Gavva,N.R., Hsu,D., Akama,T.O.,
            Yang-Feng,T. and Shen,C.K.
  TITLE     Human ITCH is a coregulator of the hematopoietic transcription
            factor NF-E2
  JOURNAL   Genomics 73 (2), 238-241 (2001)
   PUBMED   11318614
  REMARK    GeneRIF: gene expression regulation; coregulates hematopoietic
            transcription factor NF-E2
REFERENCE   7  (bases 1 to 6743)
  AUTHORS   Qiu,L., Joazeiro,C., Fang,N., Wang,H.Y., Elly,C., Altman,Y.,
            Fang,D., Hunter,T. and Liu,Y.C.
  TITLE     Recognition and ubiquitination of Notch by Itch, a hect-type E3
            ubiquitin ligase
  JOURNAL   J Biol Chem 275 (46), 35734-35737 (2000)
   PUBMED   10940313
REFERENCE   8  (bases 1 to 6743)
  AUTHORS   Winberg,G., Matskova,L., Chen,F., Plant,P., Rotin,D., Gish,G.,
            Ingham,R., Ernberg,I. and Pawson,T.
  TITLE     Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3
            protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases
  JOURNAL   Mol Cell Biol 20 (22), 8526-8535 (2000)
   PUBMED   11046148
REFERENCE   9  (bases 1 to 6743)
  AUTHORS   Wood,J.D., Yuan,J., Margolis,R.L., Colomer,V., Duan,K., Kushi,J.,
            Kaminsky,Z., Kleiderlein,J.J., Sharp,A.H. and Ross,C.A.
  TITLE     Atrophin-1, the DRPLA gene product, interacts with two families of
            WW domain-containing proteins
  JOURNAL   Mol Cell Neurosci 11 (3), 149-160 (1998)
   PUBMED   9647693
REFERENCE   10 (bases 1 to 6743)
  AUTHORS   Perry,W.L., Hustad,C.M., Swing,D.A., O'Sullivan,T.N., Jenkins,N.A.
            and Copeland,N.G.
  TITLE     The itchy locus encodes a novel ubiquitin protein ligase that is
            disrupted in a18H mice
  JOURNAL   Nat Genet 18 (2), 143-146 (1998)
   PUBMED   9462742
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL356299.16, AL705688.1,
            AK315212.1, AL109923.29, AA730741.1 and BG928040.1.
            
            On Jun 2, 2019 this sequence version replaced NM_031483.6.
            
            Summary: This gene encodes a member of the Nedd4 family of HECT
            domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases
            transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein
            substrates, thus targeting specific proteins for lysosomal
            degradation. The encoded protein plays a role in multiple cellular
            processes including erythroid and lymphoid cell differentiation and
            the regulation of immune responses. Mutations in this gene are a
            cause of syndromic multisystem autoimmune disease. Alternatively
            spliced transcript variants encoding multiple isoforms have been
            observed for this gene. [provided by RefSeq, Mar 2012].
            
            Transcript Variant: This variant (2) lacks an exon in the 5' coding
            region, but maintains the reading frame, compared to variant 1. The
            encoded isoform (2) is shorter than isoform 1. Both variants 2 and
            5 encode the same isoform (2).
            
            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 :: SRR1803616.210367.1,
                                           SRR1803611.130987.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000374864.10/ ENSP00000363998.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2                 AL356299.16        92650-92651
            3-94                AL705688.1         42-133
            95-2764             AK315212.1         92-2761
            2765-6114           AL109923.29        84937-88286
            6115-6363           AA730741.1         7-255
            6364-6743           BG928040.1         86-465              c
FEATURES             Location/Qualifiers
     source          1..6743
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20q11.22"
     gene            1..6743
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /note="itchy E3 ubiquitin protein ligase"
                     /db_xref="GeneID:83737"
                     /db_xref="HGNC:HGNC:13890"
                     /db_xref="MIM:606409"
     exon            1..77
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            78..154
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            155..245
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     CDS             176..2764
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /EC_number="2.3.2.26"
                     /note="isoform 2 is encoded by transcript variant 2;
                     atrophin-1 interacting protein 4; NFE2-associated
                     polypeptide 1; itchy E3 ubiquitin protein ligase homolog;
                     HECT-type E3 ubiquitin transferase Itchy homolog"
                     /codon_start=1
                     /product="E3 ubiquitin-protein ligase Itchy homolog
                     isoform 2"
                     /protein_id="NP_113671.3"
                     /db_xref="CCDS:CCDS13234.1"
                     /db_xref="GeneID:83737"
                     /db_xref="HGNC:HGNC:13890"
                     /db_xref="MIM:606409"
                     /translation="MSDSGSQLGSMGSLTMKSQLQITVISAKLKENKKNWFGPSPYVE
                     VTVDGQSKKTEKCNNTNSPKWKQPLTVIVTPVSKLHFRVWSHQTLKSDVLLGTAALDI
                     YETLKSNNMKLEEVVVTLQLGGDKEPTETIGDLSICLDGLQLESEVVTNGETTCSESA
                     SQNDDGSRSKDETRVSTNGSDDPEDAGAGENRRVSGNNSPSLSNGGFKPSRPPRPSRP
                     PPPTPRRPASVNGSPSATSESDGSSTGSLPPTNTNTNTSEGATSGLIIPLTISGGSGP
                     RPLNPVTQAPLPPGWEQRVDQHGRVYYVDHVEKRTTWDRPEPLPPGWERRVDNMGRIY
                     YVDHFTRTTTWQRPTLESVRNYEQWQLQRSQLQGAMQQFNQRFIYGNQDLFATSQSKE
                     FDPLGPLPPGWEKRTDSNGRVYFVNHNTRITQWEDPRSQGQLNEKPLPEGWEMRFTVD
                     GIPYFVDHNRRTTTYIDPRTGKSALDNGPQIAYVRDFKAKVQYFRFWCQQLAMPQHIK
                     ITVTRKTLFEDSFQQIMSFSPQDLRRRLWVIFPGEEGLDYGGVAREWFFLLSHEVLNP
                     MYCLFEYAGKDNYCLQINPASYINPDHLKYFRFIGRFIAMALFHGKFIDTGFSLPFYK
                     RILNKPVGLKDLESIDPEFYNSLIWVKENNIEECDLEMYFSVDKEILGEIKSHDLKPN
                     GGNILVTEENKEEYIRMVAEWRLSRGVEEQTQAFFEGFNEILPQQYLQYFDAKELEVL
                     LCGMQEIDLNDWQRHAIYRHYARTSKQIMWFWQFVKEIDNEKRMRLLQFVTGTCRLPV
                     GGFADLMGSNGPQKFCIEKVGKENWLPRSHTCFNRLDLPPYKSYEQLKEKLLFAIEET
                     EGFGQE"
     exon            246..387
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            388..512
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            513..650
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            651..696
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            697..854
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            855..1044
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1045..1140
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1141..1315
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1316..1385
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1386..1470
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1471..1599
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1600..1672
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1673..1744
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1745..1833
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1834..1993
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1994..2127
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2128..2268
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2269..2389
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2390..2494
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2495..2591
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2592..2664
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2665..6743
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5458..5463
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /note="hexamer: AATAAA"
     polyA_site      5478
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /note="major polyA site"
     regulatory      6342..6347
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /note="hexamer: ATTAAA"
     polyA_site      6363
                     /gene="ITCH"
                     /gene_synonym="ADMFD; AIF4; AIP4; NAPP1"
                     /note="major polyA site"
ORIGIN      
        1 agtagctgtg gtcggggctc gggaccggct gccatcttag tctagggact gaggagtcgc
       61 cgccgccccg agtcccggta ccatgcattt cacggtggcc ttgtggagac aacgccttaa
      121 cccaaggaag tgactcaaac tgtgagaact tcaggttttc caacctattg gtggtatgtc
      181 tgacagtgga tcacaacttg gttcaatggg tagcctcacc atgaaatcac agcttcagat
      241 cactgtcatc tcagcaaaac ttaaggaaaa taagaagaat tggtttggac caagtcctta
      301 cgtagaggtc acagtagatg gacagtcaaa gaagacagaa aaatgcaaca acacaaacag
      361 tcccaagtgg aagcaacccc ttacagttat cgttacccct gtgagtaaat tacattttcg
      421 tgtgtggagt caccagacac tgaaatctga tgttttgttg ggaactgctg cattagatat
      481 ttatgaaaca ttaaagtcaa acaatatgaa acttgaagaa gtagttgtga ctttgcagct
      541 tggaggtgac aaagagccaa cagagacaat aggagacttg tcaatttgtc ttgatgggct
      601 acagttagag tctgaagttg ttaccaatgg tgaaactaca tgttcagaaa gtgcttctca
      661 gaatgatgat ggctccagat ccaaggatga aacaagagtg agcacaaatg gatcagatga
      721 ccctgaagat gcaggagctg gtgaaaatag gagagtcagt gggaataatt ctccatcact
      781 ctcaaatggt ggttttaaac cttctagacc tccaagacct tcacgaccac caccacccac
      841 cccacgtaga ccagcatctg tcaatggttc accatctgcc acttctgaaa gtgatgggtc
      901 tagtacaggc tctctgccgc cgacaaatac aaatacaaat acatctgaag gagcaacatc
      961 tggattaata attcctctta ctatatctgg aggctcaggc cctaggccat taaatcctgt
     1021 aactcaagct cccttgccac ctggttggga gcagagagtg gaccagcacg ggcgagttta
     1081 ctatgtagat catgttgaga aaagaacaac atgggataga ccagaacctc tacctcctgg
     1141 ctgggaacgg cgggttgaca acatgggacg tatttattat gttgaccatt tcacaagaac
     1201 aacaacgtgg cagaggccaa cactggaatc cgtccggaac tatgaacaat ggcagctaca
     1261 gcgtagtcag cttcaaggag caatgcagca gtttaaccag agattcattt atgggaatca
     1321 agatttattt gctacatcac aaagtaaaga atttgatcct cttggtccat tgccacctgg
     1381 atgggagaag agaacagaca gcaatggcag agtatatttc gtcaaccaca acacacgaat
     1441 tacacaatgg gaagacccca gaagtcaagg tcaattaaat gaaaagccct tacctgaagg
     1501 ttgggaaatg agattcacag tggatggaat tccatatttt gtggaccaca atagaagaac
     1561 taccacctat atagatcccc gcacaggaaa atctgcccta gacaatggac ctcagatagc
     1621 ctatgttcgg gacttcaaag caaaggttca gtatttccgg ttctggtgtc agcaactggc
     1681 catgccacag cacataaaga ttacagtgac aagaaaaaca ttgtttgagg attcctttca
     1741 acagataatg agcttcagtc cccaagatct gcgaagacgt ttgtgggtga tttttccagg
     1801 agaagaaggt ttagattatg gaggtgtagc aagagaatgg ttctttcttt tgtcacatga
     1861 agtgttgaac ccaatgtatt gcctgtttga atatgcaggg aaggataact actgcttgca
     1921 gataaacccc gcttcttaca tcaatccaga tcacctgaaa tattttcgtt ttattggcag
     1981 atttattgcc atggctctgt tccatgggaa attcatagac acgggttttt ctttaccatt
     2041 ctataagcgt atcttgaaca aaccagttgg actcaaggat ttagaatcta ttgatccaga
     2101 attttacaat tctctcatct gggttaagga aaacaatatt gaggaatgtg atttggaaat
     2161 gtacttctcc gttgacaaag aaattctagg tgaaattaag agtcatgatc tgaaacctaa
     2221 tggtggcaat attcttgtaa cagaagaaaa taaagaggaa tacatcagaa tggtagctga
     2281 gtggaggttg tctcgaggtg ttgaagaaca gacacaagct ttctttgaag gctttaatga
     2341 aattcttccc cagcaatatt tgcaatactt tgatgcaaag gaattagagg tccttttatg
     2401 tggaatgcaa gagattgatt tgaatgactg gcaaagacat gccatctacc gtcattatgc
     2461 aaggaccagc aaacaaatca tgtggttttg gcagtttgtt aaagaaattg ataatgagaa
     2521 gagaatgaga cttctgcagt ttgttactgg aacctgccga ttgccagtag gaggatttgc
     2581 tgatctcatg gggagcaatg gaccacagaa attctgcatt gaaaaagttg ggaaagaaaa
     2641 ttggctaccc agaagtcata cctgttttaa tcgcctggac ctgccaccat acaagagcta
     2701 tgagcaactg aaggaaaagc tgttgtttgc catagaagaa acagaaggat ttggacaaga
     2761 gtaacttctg agaacttgca ccatgaatgg gcaagaactt atttgcaatg tttgtccttc
     2821 tctgcctgtt gcacatcttg taaaattgga caatggctct ttagagagtt atctgagtgt
     2881 aagtaaatta atgttctcat ttagatttat ctcccagtga tttctactca gcgtttccag
     2941 aaatcaggtc tgcaaatgac tagtcagaac cttgcttaac atgagatttt aacacaacaa
     3001 tgaaatttgc cttgtcttat tccactagtt tattccttta acaacaatat tttatgtgtg
     3061 tcaaaagtct cacttgggag tagtgttttt ttcttttaga cattctgcag acatgcaggg
     3121 aagtcctttg gtaactgcaa tatacaagat tttcctatta agcctcttgg taagaggcat
     3181 ttgttaaaag tgcaagctta ctcctgcttc tggggatgtg agcaaaattc gggcttgtgt
     3241 tctccctctc attttagtct gacttgacta ttgtttttcc tttctggcgc atgaatccat
     3301 acatcattcc tggaagtgag gcaagactct tgcatctcta caaagtagtt ttgtcaattt
     3361 gaattcaggg aaaagttggt cacagcctgc aaatgacttc atttggaagt ctgattgttt
     3421 cagttgcctg acaaatacta cactttacaa acaatgttaa cactgtgatt ccttcattgt
     3481 tttaagaagt taacctaggg ccgggcatgg tggctcatac ctgtaatcct agcactctgg
     3541 gaggccgagg caggaggatc cctttagccc aggagttaaa gaccagcctg ggcaacatag
     3601 ggagaccctg tctttttttt gggcagcgtg gtgggggata aataaataaa aggaaaaaaa
     3661 acttagccta gaattagaat taatttaatt gaattcatct aaagatgtct ctggtgattt
     3721 ttatatgttc cgctatataa ttgatgcttt atagttttat cataatccaa caacttcagt
     3781 tatatttaat tattgttaag gagtttaaga ctagaaagac tagagtgctt tctagtccaa
     3841 atagaggtca gtgaaacagc ttttgacatc agattttcat ttgagaggga gagctgtggt
     3901 actggctaaa aagaaaggaa gataacatcc agtaaccaca ggaatatatt ctctgtgaat
     3961 taaaagtctt caaagttatc atttctctga catatgttgg agtagtcatt tccattcttt
     4021 acattgtcat gaactggatt gataaccctc atctgcaata ttttcacccc taaaattttt
     4081 aacagggttt cctttttttc tcacgactat ttaagtttag attgctccat tattaactga
     4141 ttaatgcact ttgaagttct ctggaattaa ttattttaac ttggcctagc ttcgactgtc
     4201 aaggtggctg ttataaattt gacttcattg gcagtggatg aagcctaagc cagctgagtc
     4261 tctatcatag ctgaaccctg aggacagcct catagctcat gtatcaggga cttttgccac
     4321 atttcagagg catagcatga acaagtaata ttaagccaag aataagcagc agaaccctgt
     4381 tccatatgga aaaaagaaaa acaatttttt gtccctaatg ttcttccttt tacatcctgg
     4441 aacaacaata aaaacatttt tttaaacttg tctactgtaa gatactgcca tcataaagca
     4501 gagacttaca tgagtgaaag ggttgcctca tcaagcagct cagtgtaaat ggggaggcta
     4561 ggctctcccc agccctatgg tttttttatt tcatgtaccc caggaaatac tgtgtggttt
     4621 ctaaaagccc tggttgttaa aagtagggac tctgcctttt tgttggtagg gagaaaaaac
     4681 gctattgctt tgtcttacag agcgaatgtc tgccaactac ccgttcatta tataagtctg
     4741 aacttggtaa tatatggcta atgaagatta agccctctat aaagacttcc tgttgaggtg
     4801 aattctcata ctgaaatgta gttacctaca atatttacta gagatttatg aaattaaatt
     4861 aagagataat gtaagaaaat acattttttt ggttctatat aatgcttcat gattcattta
     4921 gggacctaga aatattgtgt gaaaatatat aaatatcacc caaaaggctt tctgccctat
     4981 atttttaaaa tacagaatag ttatatttga agtagccctg gccctagttc tatagggctt
     5041 ggctatttaa tatttttatg gaagaagtgt ttagttctgg aaaaggtaaa tgcttgtata
     5101 tatttttgca gcctgggatc tccctactcc attttttcct ttaatttaag tggccacatg
     5161 tatatgtctt ccctgctgtg ttaggaaaat gggggctgga tatcccaaga atcagaggtt
     5221 atataaaaat actgcaaata gaccgcagac ataaatatct accaaatgct atcttaaatt
     5281 ttggtccaaa ctgaacatat ggaaatagat ttattgtaag tatttactta gagctttttc
     5341 ttaaatctga actaacttgc ttttagaagt ctttttcttt gtaagcattg taaatgctaa
     5401 taaatcctgt taattttttt tttttttttt tttttttttt actgcatgtt acattgaaat
     5461 aaaaacaaag taaaatgagc aattgcctta ttgttctgct cttttgcagg gggtgggggt
     5521 tggggaagac agcattccac agcctggtca ggagggaagg acctcacttg tttcatcaaa
     5581 tggagtggtt taaaactgat caagcagctc ataataatga attcctgctc tgtcttttat
     5641 tatcttatgt cagagtgcag caaaatctca tttcataaga cttacaataa ctctatttaa
     5701 aattcaggta ttgtactcgg gaggctgagg tgggaggatc ccaggagttc aaatcctgcc
     5761 tgggcaacat agcaagaccc tgtctcttaa aaaaacaaaa agacatattc aggtactgat
     5821 ttttcatcaa gagattgaca taccaatgat cagaaatttt agtgaaactt gactcaacta
     5881 tacacaaagt tctcatccta aatgaactat ttcagtcaag cccactctac cactttttac
     5941 ttatctggtt aataatccga aatgttaccg gggttgactc acggaattaa atttttcctc
     6001 tatttttata tcctttcctg ttgtggatgt aacttacctt tctaaactcc tttagagtta
     6061 acgacttcta tttagtattg ttggtatctc cagcccccct cctttttttg tttttctttt
     6121 agttatttac tttgtttgta taatttgctt tcattaacta aaaatggaat tggcagcact
     6181 ggattgtata ttactgtatt aagagtacct ttgttttctt gatctgttac ttttaatact
     6241 caggtaatgc tacaaatatt acagggagtc aaatgctttt ataaagttcc ttcagtggtt
     6301 gcctcacttg cgttttccta caagatgtaa gactgtttat aattaaactt ttttggtcct
     6361 tcatttgcat gcttttctat cagtcttggg taaggagggg tctctttcct ctctccccgg
     6421 ccccaccttc tgagacttat atgtgaccag gtcacataga tttctgcctc tctgcttttt
     6481 taagtggcaa gttacagccc atctggattg tggtattgtt cccagaccaa atcaagggtt
     6541 ggactgctta ttctcgcagc ccaataatga ggtgcagatg aactgagaaa ggagggagtt
     6601 tatttctgta accaggtatg gggagaaagc ctggaaatga tcccaagacc aactcaaaac
     6661 tacaaagttt tccagagctt atttacatta taagctatat gtctacatgt gagtgtacat
     6721 tcatctaaag acataagtga ttc
//
