LOCUS       NM_000246              16061 bp    mRNA    linear   PRI 10-FEB-2025
DEFINITION  Homo sapiens class II major histocompatibility complex
            transactivator (CIITA), transcript variant 2, mRNA.
ACCESSION   NM_000246
VERSION     NM_000246.4
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 16061)
  AUTHORS   Sreenivasan,S., Heffren,P., Suh,K.S., Rodnin,M.V., Kosa,E.,
            Fenton,A.W., Ladokhin,A.S., Smith,P.E., Fontes,J.D. and
            Swint-Kruse,L.
  TITLE     The intrinsically disordered transcriptional activation domain of
            CIITA is functionally tuneable by single substitutions: An
            exception or a new paradigm?
  JOURNAL   Protein Sci 33 (2), e4863 (2024)
   PUBMED   38073129
  REMARK    GeneRIF: The intrinsically disordered transcriptional activation
            domain of CIITA is functionally tuneable by single substitutions:
            An exception or a new paradigm?
REFERENCE   2  (bases 1 to 16061)
  AUTHORS   Forlani,G., Shallak,M., Gatta,A., Shaik,A.K.B. and Accolla,R.S.
  TITLE     The NLR member CIITA: Master controller of adaptive and intrinsic
            immunity and unexpected tool in cancer immunotherapy
  JOURNAL   Biomed J 46 (5), 100631 (2023)
   PUBMED   37467968
  REMARK    GeneRIF: The NLR member CIITA: Master controller of adaptive and
            intrinsic immunity and unexpected tool in cancer immunotherapy.
            Review article
REFERENCE   3  (bases 1 to 16061)
  AUTHORS   Santharam,M.A., Shukla,A., Levesque,D., Kufer,T.A., Boisvert,F.M.,
            Ramanathan,S. and Ilangumaran,S.
  TITLE     NLRC5-CIITA Fusion Protein as an Effective Inducer of MHC-I
            Expression and Antitumor Immunity
  JOURNAL   Int J Mol Sci 24 (8), 7206 (2023)
   PUBMED   37108368
  REMARK    GeneRIF: NLRC5-CIITA Fusion Protein as an Effective Inducer of
            MHC-I Expression and Antitumor Immunity.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 16061)
  AUTHORS   Hos,B.J., Tondini,E., Camps,M.G.M., Rademaker,W., van den Bulk,J.,
            Ruano,D., Janssen,G.M.C., de Ru,A.H., van den Elsen,P.J., de
            Miranda,N.F.C.C., van Veelen,P.A. and Ossendorp,F.
  TITLE     Cancer-specific T helper shared and neo-epitopes uncovered by
            expression of the MHC class II master regulator CIITA
  JOURNAL   Cell Rep 41 (2), 111485 (2022)
   PUBMED   36223747
  REMARK    GeneRIF: Cancer-specific T helper shared and neo-epitopes uncovered
            by expression of the MHC class II master regulator CIITA.
            Erratum:[Cell Rep. 2022 Nov 22;41(8):111680. doi:
            10.1016/j.celrep.2022.111680.. PMID: 36417866]
REFERENCE   5  (bases 1 to 16061)
  AUTHORS   Zhu,Y., Pan,H., Han,Y., Li,T., Liu,K. and Wang,B.
  TITLE     Novel missense variant of CIITA contributing to endometriosis
  JOURNAL   Reprod Biomed Online 45 (3), 544-551 (2022)
   PUBMED   35835655
  REMARK    GeneRIF: Novel missense variant of CIITA contributing to
            endometriosis.
REFERENCE   6  (bases 1 to 16061)
  AUTHORS   Riley,J.L., Westerheide,S.D., Price,J.A., Brown,J.A. and Boss,J.M.
  TITLE     Activation of class II MHC genes requires both the X box region and
            the class II transactivator (CIITA)
  JOURNAL   Immunity 2 (5), 533-543 (1995)
   PUBMED   7749984
REFERENCE   7  (bases 1 to 16061)
  AUTHORS   Steimle,V., Otten,L.A., Zufferey,M. and Mach,B.
  TITLE     Complementation cloning of an MHC class II transactivator mutated
            in hereditary MHC class II deficiency (or bare lymphocyte syndrome)
  JOURNAL   Cell 75 (1), 135-146 (1993)
   PUBMED   8402893
REFERENCE   8  (bases 1 to 16061)
  AUTHORS   Mann,D.M. and Yates,P.O.
  TITLE     A quantitative study of the glia of the Purkinje cell layer of the
            cerebellum in mammals
  JOURNAL   Neuropathol Appl Neurobiol 5 (1), 71-76 (1979)
   PUBMED   107465
REFERENCE   9  (bases 1 to 16061)
  AUTHORS   Pereira,S.N., Castagna,R.C., Gressler,J.F., Marques,R.S. and
            Costa,P.S.
  TITLE     [Dura-mater valve bank]
  JOURNAL   Arq Bras Cardiol 29 (4), 277-280 (1976)
   PUBMED   1008718
REFERENCE   10 (bases 1 to 16061)
  AUTHORS   Poschlova,N., Masek,K. and Krsiak,M.
  TITLE     Effect of 5,6-dihydroxytryptamine on social behaviour in mice
            [proceedings]
  JOURNAL   Act Nerv Super (Praha) 18 (3), 229-230 (1976)
   PUBMED   1007865
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC133065.3 and KF459560.1.
            
            On Aug 6, 2020 this sequence version replaced NM_000246.3.
            
            Summary: This gene encodes a protein with an acidic transcriptional
            activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding
            domain. The protein is located in the nucleus and acts as a
            positive regulator of class II major histocompatibility complex
            gene transcription, and is referred to as the 'master control
            factor' for the expression of these genes. The protein also binds
            GTP and uses GTP binding to facilitate its own transport into the
            nucleus. Once in the nucleus it does not bind DNA but rather uses
            an intrinsic acetyltransferase (AT) activity to act in a
            coactivator-like fashion. Mutations in this gene have been
            associated with bare lymphocyte syndrome type II (also known as
            hereditary MHC class II deficiency or HLA class II-deficient
            combined immunodeficiency), increased susceptibility to rheumatoid
            arthritis, multiple sclerosis, and possibly myocardial infarction.
            Several transcript variants encoding different isoforms have been
            found for this gene. [provided by RefSeq, Nov 2013].
            
            Transcript Variant: This variant (2) uses an alternate in-frame
            splice junction at the 5' end of an exon compared to variant 1. The
            resulting isoform (2) is 1 aa shorter compared to isoform 1.
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on 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 :: X74301.1, SRR18074968.2618058.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000324288.14/ ENSP00000316328.8
            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
            1-181               AC133065.3         57117-57297
            182-328             AC133065.3         75197-75343
            329-424             AC133065.3         75584-75679
            425-487             AC133065.3         78585-78647
            488-565             AC133065.3         78840-78917
            566-610             AC133065.3         81429-81473
            611-757             KF459560.1         151-297
            758-901             AC133065.3         82573-82716
            902-1066            AC133065.3         83646-83810
            1067-1135           AC133065.3         84659-84727
            1136-2786           AC133065.3         86414-88064
            2787-2945           AC133065.3         88944-89102
            2946-3017           AC133065.3         90103-90174
            3018-3098           AC133065.3         95485-95565
            3099-3191           AC133065.3         96282-96374
            3192-3278           AC133065.3         98355-98441
            3279-3362           AC133065.3         102082-102165
            3363-3446           AC133065.3         102322-102405
            3447-3544           AC133065.3         103143-103240
            3545-16061          AC133065.3         103793-116309
FEATURES             Location/Qualifiers
     source          1..16061
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16p13.13"
     gene            1..16061
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /note="class II major histocompatibility complex
                     transactivator"
                     /db_xref="GeneID:4261"
                     /db_xref="HGNC:HGNC:7067"
                     /db_xref="MIM:600005"
     exon            1..181
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     CDS             130..3522
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /EC_number="2.7.11.1"
                     /note="isoform 2 is encoded by transcript variant 2; NLR
                     family, acid domain containing; nucleotide-binding
                     oligomerization domain, leucine rich repeat and acid
                     domain containing; MHC class II transactivator type III"
                     /codon_start=1
                     /product="MHC class II transactivator isoform 2"
                     /protein_id="NP_000237.2"
                     /db_xref="CCDS:CCDS10544.1"
                     /db_xref="GeneID:4261"
                     /db_xref="HGNC:HGNC:7067"
                     /db_xref="MIM:600005"
                     /translation="MRCLAPRPAGSYLSEPQGSSQCATMELGPLEGGYLELLNSDADP
                     LCLYHFYDQMDLAGEEEIELYSEPDTDTINCDQFSRLLCDMEGDEETREAYANIAELD
                     QYVFQDSQLEGLSKDIFKHIGPDEVIGESMEMPAEVGQKSQKRPFPEELPADLKHWKP
                     AEPPTVVTGSLLVGPVSDCSTLPCLPLPALFNQEPASGQMRLEKTDQIPMPFSSSSLS
                     CLNLPEGPIQFVPTISTLPHGLWQISEAGTGVSSIFIYHGEVPQASQVPPPSGFTVHG
                     LPTSPDRPGSTSPFAPSATDLPSMPEPALTSRANMTEHKTSPTQCPAAGEVSNKLPKW
                     PEPVEQFYRSLQDTYGAEPAGPDGILVEVDLVQARLERSSSKSLERELATPDWAERQL
                     AQGGLAEVLLAAKEHRRPRETRVIAVLGKAGQGKSYWAGAVSRAWACGRLPQYDFVFS
                     VPCHCLNRPGDAYGLQDLLFSLGPQPLVAADEVFSHILKRPDRVLLILDGFEELEAQD
                     GFLHSTCGPAPAEPCSLRGLLAGLFQKKLLRGCTLLLTARPRGRLVQSLSKADALFEL
                     SGFSMEQAQAYVMRYFESSGMTEHQDRALTLLRDRPLLLSHSHSPTLCRAVCQLSEAL
                     LELGEDAKLPSTLTGLYVGLLGRAALDSPPGALAELAKLAWELGRRHQSTLQEDQFPS
                     ADVRTWAMAKGLVQHPPRAAESELAFPSFLLQCFLGALWLALSGEIKDKELPQYLALT
                     PRKKRPYDNWLEGVPRFLAGLIFQPPARCLGALLGPSAAASVDRKQKVLARYLKRLQP
                     GTLRARQLLELLHCAHEAEEAGIWQHVVQELPGRLSFLGTRLTPPDAHVLGKALEAAG
                     QDFSLDLRSTGICPSGLGSLVGLSCVTRFRAALSDTVALWESLQQHGETKLLQAAEEK
                     FTIEPFKAKSLKDVEDLGKLVQTQRTRSSSEDTAGELPAVRDLKKLEFALGPVSGPQA
                     FPKLVRILTAFSSLQHLDLDALSENKIGDEGVSQLSATFPQLKSLETLNLSQNNITDL
                     GAYKLAEALPSLAASLLRLSLYNNCICDVGAESLARVLPDMVSLRVMDVQYNKFTAAG
                     AQQLAASLRRCPHVETLAMWTPTIPFSVQEHLQQQDSRISLR"
     exon            182..328
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            329..424
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            425..487
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            488..565
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            566..610
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            611..757
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            758..901
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            902..1066
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            1067..1135
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            1136..2786
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            2787..2945
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            2946..3017
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            3018..3098
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            3099..3191
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            3192..3278
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            3279..3362
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            3363..3446
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            3447..3544
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     exon            3545..16061
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4508..4513
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /note="hexamer: TATAAA"
     polyA_site      4529
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /note="major polyA site"
     regulatory      11930..11935
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /note="hexamer: AATGAA"
     polyA_site      11948
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /note="major polyA site"
     regulatory      15924..15929
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /note="hexamer: AATAAA"
     polyA_site      15949
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
     regulatory      16034..16039
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
                     /note="hexamer: AATAAA"
     polyA_site      16061
                     /gene="CIITA"
                     /gene_synonym="C2TA; CIITAIV; MHC2D1; MHC2TA; NLRA"
ORIGIN      
        1 agtgatgagg ctagtgatga ggctgtgtgc ttctgagctg ggcatccgaa ggcatccttg
       61 gggaagctga gggcacgagg aggggctgcc agactccggg agctgctgcc tggctgggat
      121 tcctacacaa tgcgttgcct ggctccacgc cctgctgggt cctacctgtc agagccccaa
      181 ggcagctcac agtgtgccac catggagttg gggcccctag aaggtggcta cctggagctt
      241 cttaacagcg atgctgaccc cctgtgcctc taccacttct atgaccagat ggacctggct
      301 ggagaagaag agattgagct ctactcagaa cccgacacag acaccatcaa ctgcgaccag
      361 ttcagcaggc tgttgtgtga catggaaggt gatgaagaga ccagggaggc ttatgccaat
      421 atcgcggaac tggaccagta tgtcttccag gactcccagc tggagggcct gagcaaggac
      481 attttcaagc acataggacc agatgaagtg atcggtgaga gtatggagat gccagcagaa
      541 gttgggcaga aaagtcagaa aagacccttc ccagaggagc ttccggcaga cctgaagcac
      601 tggaagccag ctgagccccc cactgtggtg actggcagtc tcctagtggg accagtgagc
      661 gactgctcca ccctgccctg cctgccactg cctgcgctgt tcaaccagga gccagcctcc
      721 ggccagatgc gcctggagaa aaccgaccag attcccatgc ctttctccag ttcctcgttg
      781 agctgcctga atctccctga gggacccatc cagtttgtcc ccaccatctc cactctgccc
      841 catgggctct ggcaaatctc tgaggctgga acaggggtct ccagtatatt catctaccat
      901 ggtgaggtgc cccaggccag ccaagtaccc cctcccagtg gattcactgt ccacggcctc
      961 ccaacatctc cagaccggcc aggctccacc agccccttcg ctccatcagc cactgacctg
     1021 cccagcatgc ctgaacctgc cctgacctcc cgagcaaaca tgacagagca caagacgtcc
     1081 cccacccaat gcccggcagc tggagaggtc tccaacaagc ttccaaaatg gcctgagccg
     1141 gtggagcagt tctaccgctc actgcaggac acgtatggtg ccgagcccgc aggcccggat
     1201 ggcatcctag tggaggtgga tctggtgcag gccaggctgg agaggagcag cagcaagagc
     1261 ctggagcggg aactggccac cccggactgg gcagaacggc agctggccca aggaggcctg
     1321 gctgaggtgc tgttggctgc caaggagcac cggcggccgc gtgagacacg agtgattgct
     1381 gtgctgggca aagctggtca gggcaagagc tattgggctg gggcagtgag ccgggcctgg
     1441 gcttgtggcc ggcttcccca gtacgacttt gtcttctctg tcccctgcca ttgcttgaac
     1501 cgtccggggg atgcctatgg cctgcaggat ctgctcttct ccctgggccc acagccactc
     1561 gtggcggccg atgaggtttt cagccacatc ttgaagagac ctgaccgcgt tctgctcatc
     1621 ctagacggct tcgaggagct ggaagcgcaa gatggcttcc tgcacagcac gtgcggaccg
     1681 gcaccggcgg agccctgctc cctccggggg ctgctggccg gccttttcca gaagaagctg
     1741 ctccgaggtt gcaccctcct cctcacagcc cggccccggg gccgcctggt ccagagcctg
     1801 agcaaggccg acgccctatt tgagctgtcc ggcttctcca tggagcaggc ccaggcatac
     1861 gtgatgcgct actttgagag ctcagggatg acagagcacc aagacagagc cctgacgctc
     1921 ctccgggacc ggccacttct tctcagtcac agccacagcc ctactttgtg ccgggcagtg
     1981 tgccagctct cagaggccct gctggagctt ggggaggacg ccaagctgcc ctccacgctc
     2041 acgggactct atgtcggcct gctgggccgt gcagccctcg acagcccccc cggggccctg
     2101 gcagagctgg ccaagctggc ctgggagctg ggccgcagac atcaaagtac cctacaggag
     2161 gaccagttcc catccgcaga cgtgaggacc tgggcgatgg ccaaaggctt agtccaacac
     2221 ccaccgcggg ccgcagagtc cgagctggcc ttccccagct tcctcctgca atgcttcctg
     2281 ggggccctgt ggctggctct gagtggcgaa atcaaggaca aggagctccc gcagtaccta
     2341 gcattgaccc caaggaagaa gaggccctat gacaactggc tggagggcgt gccacgcttt
     2401 ctggctgggc tgatcttcca gcctcccgcc cgctgcctgg gagccctact cgggccatcg
     2461 gcggctgcct cggtggacag gaagcagaag gtgcttgcga ggtacctgaa gcggctgcag
     2521 ccggggacac tgcgggcgcg gcagctgctg gagctgctgc actgcgccca cgaggccgag
     2581 gaggctggaa tttggcagca cgtggtacag gagctccccg gccgcctctc ttttctgggc
     2641 acccgcctca cgcctcctga tgcacatgta ctgggcaagg ccttggaggc ggcgggccaa
     2701 gacttctccc tggacctccg cagcactggc atttgcccct ctggattggg gagcctcgtg
     2761 ggactcagct gtgtcacccg tttcagggct gccttgagcg acacggtggc gctgtgggag
     2821 tccctgcagc agcatgggga gaccaagcta cttcaggcag cagaggagaa gttcaccatc
     2881 gagcctttca aagccaagtc cctgaaggat gtggaagacc tgggaaagct tgtgcagact
     2941 cagaggacga gaagttcctc ggaagacaca gctggggagc tccctgctgt tcgggaccta
     3001 aagaaactgg agtttgcgct gggccctgtc tcaggccccc aggctttccc caaactggtg
     3061 cggatcctca cggccttttc ctccctgcag catctggacc tggatgcgct gagtgagaac
     3121 aagatcgggg acgagggtgt ctcgcagctc tcagccacct tcccccagct gaagtccttg
     3181 gaaaccctca atctgtccca gaacaacatc actgacctgg gtgcctacaa actcgccgag
     3241 gccctgcctt cgctcgctgc atccctgctc aggctaagct tgtacaataa ctgcatctgc
     3301 gacgtgggag ccgagagctt ggctcgtgtg cttccggaca tggtgtccct ccgggtgatg
     3361 gacgtccagt acaacaagtt cacggctgcc ggggcccagc agctcgctgc cagccttcgg
     3421 aggtgtcctc atgtggagac gctggcgatg tggacgccca ccatcccatt cagtgtccag
     3481 gaacacctgc aacaacagga ttcacggatc agcctgagat gatcccagct gtgctctgga
     3541 caggcatgtt ctctgaggac actaaccacg ctggaccttg aactgggtac ttgtggacac
     3601 agctcttctc caggctgtat cccatgagcc tcagcatcct ggcacccggc ccctgctggt
     3661 tcagggttgg cccctgcccg gctgcggaat gaaccacatc ttgctctgct gacagacaca
     3721 ggcccggctc caggctcctt tagcgcccag ttgggtggat gcctggtggc agctgcggtc
     3781 cacccaggag ccccgaggcc ttctctgaag gacattgcgg acagccacgg ccaggccaga
     3841 gggagtgaca gaggcagccc cattctgcct gcccaggccc ctgccaccct ggggagaaag
     3901 tacttctttt tttttatttt tagacagagt ctcactgttg cccaggctgg cgtgcagtgg
     3961 tgcgatctgg gttcactgca acctccgcct cttgggttca agcgattctt ctgcttcagc
     4021 ctcccgagta gctgggacta caggcaccca ccatcatgtc tggctaattt ttcattttta
     4081 gtagagacag ggttttgcca tgttggccag gctggtctca aactcttgac ctcaggtgat
     4141 ccacccacct cagcctccca aagtgctggg attacaagcg tgagccactg caccgggcca
     4201 cagagaaagt acttctccac cctgctctcc gaccagacac cttgacaggg cacaccgggc
     4261 actcagaaga cactgatggg caacccccag cctgctaatt ccccagattg caacaggctg
     4321 ggcttcagtg gcagctgctt ttgtctatgg gactcaatgc actgacattg ttggccaaag
     4381 ccaaagctag gcctggccag atgcaccagc ccttagcagg gaaacagcta atgggacact
     4441 aatggggcgg tgagagggga acagactgga agcacagctt catttcctgt gtcttttttc
     4501 actacattat aaatgtctct ttaatgtcac aggcaggtcc agggtttgag ttcataccct
     4561 gttaccattt tggggtaccc actgctctgg ttatctaata tgtaacaagc caccccaaat
     4621 catagtggct taaaacaaca ctcacattta ttctgctcac atatctgtca tttgagcagg
     4681 gctcagcggg gacagctcct tctgtcctac tctgtgtcag gtggggcagc ttgagggttg
     4741 ggctggtgtc acctgaagac tcattcttct gtacgtctga caggcaatgc tggctgttgg
     4801 ctgggggcct cagtgccact acggaatagt tggctaggac ccctccatgt gggctagttg
     4861 ggcttcctca tagtatggtg gctgggttgg agggtgtccc aaaaagaaag gaggggatag
     4921 agagagacca cttttcataa cctagcctta gaagtcacac agtattactt ctgctacata
     4981 tatatgtttt aagaggcagg gtctcactct gtcgcccagt ctggaatgca gtggtatgat
     5041 cacggctcac tgcagcctca acctcctggg ctaagtgatc ctcccacctc agcctcccga
     5101 atagctggga ctacaggtgt gagtcaccaa gcccagttaa tctttagttt tatttttgta
     5161 gagccagggt ctcactatgt tgcccaggca ggtcttgaac tcctggcctc aagtgattct
     5221 cctgcctcag cctcccaaag tgctgggatt acaggtgtga accaccacac ccagcccact
     5281 tctgccatat tctgttggcc agtgtgacaa ggattgctac tgtcctaccc accctccttt
     5341 caccacatgt gcacatgcac gtgtgtgcac gtacacacac atacacacac acgcgtgcac
     5401 acaccagagc ccaccttggc tcaagtcctc ttttctgaga ggacttttct ttgtggcttc
     5461 ctaaaattca gtggaaaatt aattgtttgg ggatgagaaa ggttgaagca ccaaaagctt
     5521 accaagggga atgtttgcct ctgcctctga cacacagctc tgtcctggga gtgagctggt
     5581 ttttagcgga gacggagtcc caccttggct gcagggagtc cgaaagggac ttggaagctc
     5641 cgctttctac ccagcgagct gccggcacga ctgttgcttt tcactcgggc atagtctgct
     5701 cagaagcccc aattcaagac atcttagctt actcctggtg gcagtgggag ctgcctgttc
     5761 agctccagct caccagcccc agtgcccaca ggatcagtct gattcccaag ctctgctcct
     5821 ctccccagca agtgagagct gggtgtcaag agggtctgag gaatccagac ccggctgcgt
     5881 ggttgatgat ctttgcagac aggcaagcac ctcctgcctc gaactggctg caaagggtat
     5941 caggtgctgc catccaggtt cagcttgtaa atagctcagg tgtcaccctg caagggatcc
     6001 ctgcacttgc agactctaca gaggccatgg gcctcctgtg tgtgcgccta caggagtgag
     6061 cactaaggtg tgctctgatc atccactgtg ccatgtgcca ggtttttggt ctgacccact
     6121 gcttttggtc tgtgtgatga tgaaatgagg tcagagcctg cagttattaa cactaacgat
     6181 ttgttaatga tagctactgt ttattatttt atttaatttt tttgagacag agttttcact
     6241 cttattgccc acgctggagt gcagtggcat gatctcggct cactgcaacc tctgcctcct
     6301 gggttcaagc aattctccca cctcagcctc ccaagtagct gggattacag gcatgcacca
     6361 ccacgcctgg ctaatttttg tatttttagt agagatggag tttcaccatg ttggccaggc
     6421 tggtaatctg cctgccttgg cctcccaaag tgctgggatt acaggggtga gccaccgcac
     6481 ccggccacta ctgtttattt aatgagcaga tacatgcaaa gcccttatca cagtgcaagg
     6541 gaaattcaaa gcgctcagaa agtattagct caataagtga tgactgtgtg ccagacactg
     6601 tgctaaactc ctactcaaga gggataagag tctaggggca agtggcagag actctagaac
     6661 gagattgcct gggctcaacg cccacctcac cacttactta tgcaagctag ttctctgtgc
     6721 ctcagtctcc tcatttgtaa aatgggcata accacagcac cttctttata ggattatgtg
     6781 aaggtgtggt gagctaatac gttaagaatt ggagctcaat aacatgttgg ctgtcattat
     6841 tacatatatc tgtgtttcat tcttgcctct ggctggaatg ttcttcccag ctctccatat
     6901 ggctgatttc tcatccttcg ggacttgccc cattctccaa ccccatcact agttttatct
     6961 ttttcactta tttatgcagt ctgctcttgt cctaggacat gagctccagg agggcgggaa
     7021 acatctcgct ttgtacactg ctgtgccctc tgtacccagc aaggcgcctg tgtataatag
     7081 gtgctcaata acataaaatg aacaaataat cctcacctaa cggtttcatt cattctgcaa
     7141 atacatactg acagcacagt catgaataag atgttcctgc cctggtgagt cttatatttt
     7201 agcaaattaa aaaaactctt tggacagggc tgccaggtga ggttggccag tctgtacact
     7261 gcacaaaggc acctgggaca agggggaaca tgggggctgc aaaccagtct gggttctgct
     7321 tgccaaactg ggagtcctgg tgtggagcct tttaacccag aggggcatct tttcgtagtt
     7381 aacgcacagt catcgtaaga tgtggataaa ttactgtctc cgtgtcacag atctaagtga
     7441 tacttatagt cacactccta taaaggaatg gacttctgac ttctttggag gacctctctg
     7501 cagggacagg cacagtgtgc cggaagtgcc cctgaacccc atttgtcagg tggtaaagcg
     7561 ctgctcggag gaatcagggc atgatagtgc aattccatgt ccagtggatt gtaagtccac
     7621 gcaccttcca aatggtcact cttcctcgca ggcctctctc tgcatacaaa tgtctccctc
     7681 ctgacgctca cctttttccc tggggctctc aaatgtcttc ttttcagatt tcgtagcttt
     7741 tctttcttta gcatcacttg agggcaagtg gtgctccaac tgtctccccc cagagttctg
     7801 ccgcctgtac tctcccacac ctcagtctcc tcgcctgtag aaaggggtca atcgtttgaa
     7861 ccctgcttca cttggtgtgt atgtgaaggt gctttgaaat caagtgctct gcaaactgga
     7921 gagaattact gcttgtattc cgtgaaacta caagctccca attccactca tttaatccct
     7981 ctcttgctct gttgcccagg ctggaatgca gtggcatgat ctcaactcac tgcaacctct
     8041 gcctccctgg tttcaagcaa ttctcctgcc tcagcctccc gagtagctgg gactataagt
     8101 gtgcgccact atgcctggct aatttttttg tatttttagt agagatgggg tttcaccgtg
     8161 gtggccaggc tggtctcgaa ctcctaacct caagtgatct gcccgcctcg gccttccaaa
     8221 gtgctgggat tacaggcatg agccaccatg ccaagccctt cccccctatc tttaatgaag
     8281 gtctaccatg tgcctgacac aggggatacc cacccccact tctatgggat tcaggcctgg
     8341 tttccagctt ggccttcagg cttttcccac cacaccccaa atgctgtccc tggcttgtgg
     8401 agtggggcag ggggccagcc tgggactttc acgccagccc gactggggca gactctctca
     8461 accccactgg atcttctgct gtttgtcagc cacaaggttc tgcctagaac tcctttcccg
     8521 aatctcaaag ttaaaaaaaa aggcagggcc ccaggggttg gagttgcata catttttttt
     8581 taatccaaag aagtaagcct cctaagtatt gcttagacag gtttatcaga attaagtagg
     8641 cacaacactc atactttcag aaaagcattt ccagccaggg gagtaacgtg gcactcacca
     8701 gcatgatgtc tgttttgcca acttgctgaa gaacgagtaa cctgaaatga aggagcgaga
     8761 atcccaccct cagcccccca acagcttcct cagcttcttt ttcttctgag tcacccctga
     8821 aacagtcgct gcatctaaga ccagcctcgg gctaaaccca gctggcctga aggctcaact
     8881 cacatcaaac ggagctggga gtcgcttttg cgtgtgtccg cagtttgaag tgtcctctcc
     8941 gaaggtgaag tgggggaagc aggtgcgctc cgggatgaag tgcagggagg caaactctgg
     9001 ctgggttcct gtaaacatcc atcgcagctg caaataatca gaagccaagg ccaggccatc
     9061 gatttgacac tgcaggcaga tgaggtcttg ggatgcctct tgcgttcccc cttctgtggg
     9121 agcaggtgcc ttcccaacct cagcactcag tcccaatctc tcttccactc tcctgggttc
     9181 aaacaggaac ctctctgttg gcacgaagct tttgagggga gcaggtctaa caagaaggaa
     9241 aaaggggggt tattagcacg gaagccccac cctgccacca ggttggctgg ggacagggac
     9301 caatccacca ggctcgggag gcttggggtg gggcagggaa gtcttcctcc atccctcaaa
     9361 tttagggaac cactgggagc cccagactca ggctgaaaat gtctttctgc aaatataaaa
     9421 ctctttttaa tgaatttgcc taatttctca gagaccctgg gctggagaac cagtgcaatg
     9481 tcacacggga gaggaaggac tgtcctgttt attgggaggg aggaggggga tgctggtgca
     9541 gcctgctcag gagtcaccca gggtctgagg gctgacttgc agctctgggc cagctgagcc
     9601 agcgctgggt agtgggcagg gcttggcaac accttccacc ttgcccggaa aaatgctttg
     9661 caacctacag gaaggcaata gccacagcca agttactcag cagccccact tggctctttc
     9721 tcccaggatg cagcatcatc tccatggcct ggccccctgg cacgtccccg tttcccactg
     9781 ccttctctgt gtgcctagcc gggtgccagt gtctctgtag cacctcgtgt tcccatgccc
     9841 aacccctctg cagccccctc aagccctgct ctgattccaa gcctcatctc ccagctcact
     9901 atcctttccg caaacttcac tgaacatctc gcagaacttg tatgttaaac atgtgacatg
     9961 tattgttgtt tgacagggtg ctattgacat ttggggtagg acaattcttg gaggtggggt
    10021 ggctgttctg ggcactgagc atttagcagc atctctggct ccaggccact aaatgccagt
    10081 agcacccctg gccactggaa caactaaaaa tgccctccta ccctatttcc aaggtcgacc
    10141 taagggggcg gaactgtttc cattgagacc catgcatcgt ataggataag aaactgaggt
    10201 tcttatcatt taataggata agaaattgag gttcagagaa gccaagtaac ctgcctaaag
    10261 atgcacagct atgagaggca aagctggcac tggcttggta ataacgatgg aaacggtctg
    10321 aatgagagca ggtaccattt cctgagctct tagcagacgc tgaggaccct gctaagtgcc
    10381 atgagacctt agcagaggct gtgggtgccc cgccccattc cctccactca ctcttccttg
    10441 caggtcgacc tgcccttctt tgctgaggcc tttctctgcc tccagagcct gcttggtcct
    10501 caggctgtaa gtgcaggcag agctaatgtc tctccatagc tgccctccac cagcctgctc
    10561 ctgagacacc tgctggccag cagcctgaag cagaatcctt tactcagatt cagccgcaca
    10621 gatgctcact gcagagatct ccaaggcctg tggtcatcct tgagcccatc tcagatttgt
    10681 gtggataggg tgttagagaa catggaatca gctggataga gtggttcatg cttgtaatcc
    10741 cagcactttg ggaggctggg gtgggaggat cacttgaggc caggagtttg agaccagcct
    10801 gggcaacaca gtgagactgt ctctataaaa aatttaaaaa ttagccaggc atagtgtagt
    10861 ctcagctact tggaaggctg aggcaggagg attgcgtgag cccagcagtt caaggctgca
    10921 gtgaactatg actgtgcccc tgcacccagc ctgggtgaca gagaccctgt ctcaaaaaaa
    10981 agagaagatg gaatcactcg gtgaggacct cactcctctc ccagtcctgt gaccacaaac
    11041 cgcatccccg acagtcccag ccaggcgcta gtctggctgt agctgccctc ttgtgtgcag
    11101 atctccagtc tgaatgggct acacgtggaa tttactaaca ctccggtttt cattgtgttt
    11161 atctgtaggg ttaccttcta tttatagcaa gtgatgccaa gtttccattt ctggtagtaa
    11221 tatagttttt cttttccaag tcgctcacac ctgtaatccc aacactttgg gaggctaagg
    11281 tgggtggatc agttgagatc aggagtttga gaccagcctg gccaacatgg cgaaatgagg
    11341 tcaagactag cctggccaac atggcgaaac cgcgtctcta ctaaaaacaa acaaacaaaa
    11401 atacaaaatt cgctgggcat ggtggcaggt gcctgaggtc ccagctactc gggaggctga
    11461 ggcagaagaa tcgcttgagc tagggaggca gaggttgcag tgagccgaga tcacgccact
    11521 gcactatagc ctaggtgaca gagtgagact ctgtctcaaa aaaacacaaa agtttctctt
    11581 ttcaaaacat tttactttaa aaggagccaa tttaaagaaa actgttaata gttcaggtaa
    11641 caggcagata caggaaaagc tgctgacagt gttgtatgag gtttgaggat tttgatccaa
    11701 gctggtccca ctcagtccat agcagagaat gaaagggccc agagagggtg gtgacctctg
    11761 cctgaagtca cacagtgagt cgaggacagg gaggtgaccc caggtttcta tgtgtagggc
    11821 gggaggatgt tctgggacac agttcaattc tcatttgtca cacactttgg ctattagaga
    11881 tcaacccctt cgctcctgtg tcttgcaatg gcagccttgg caaacgctaa atgaaaatcg
    11941 tgacaacact tgtgttatga agcatttact ttgtgttcac cttgtactac tcgaactcat
    12001 gtcttaactc acttatccct caaaaacaac tctaggaggt agggccaagt aggaccatca
    12061 tccctgcatt tcacatggag ctcagagagg ttaagcaagc cgtgcaaggc cacacagctc
    12121 ataaatggca gagccaggat ttgaaccccc gtggcctgac cccaaagccg aaaccactcg
    12181 gcactgcagg ttcgtccctt ttctctgaga tgggggtatc caatcttttg gcttccctgg
    12241 gccacagtgg aagaactgtc tggggccaca tataaaatat actaatgata gctcatgagc
    12301 taaaaaataa aacaaaatca cacacacaca cacaaaaaaa cacaaaccaa aaaaaaaatt
    12361 cttttttttt tttttttttt gagacagggt cttgctttgt cacccaggct ggagggcagt
    12421 ggcatgatct tggctcactg cagttccagg ttcaagcaat tctcatgcct cagcctcctg
    12481 agtagctggg actacaggcg catgtcacca tgcctggcta attgatgtat tttttagtag
    12541 agatggggtt tcaccatgtt ggccaggcta aaatctcata acgttttaag aaagtttatg
    12601 aatctgtgtt gggccacagt caaagccgtc ctgagctgta tgcagcctac aggccgcacc
    12661 acggattgaa caagtttctt ctaaggcatc aagagcccca ggctgaaaag caccccagag
    12721 ctggagctta tagaacccag ggcagcaggt tctccaacct tctgacatca tcagagcaca
    12781 gcagacaagt tatcagccac tagatttttt tccccctttc tgaaactgta acctttcatt
    12841 ccagccattc cccagagctg gacagaggac gtggctggct ggctggtttc tgtagtcaga
    12901 atgacagttg ggtgctagat ccccttcgtg aagcaatgtc ttagctcagt aactctgcag
    12961 agaagctgcc tggttcagga tgtggcttaa gtaagaagat ggccctggcg ttttacgcgc
    13021 actggtgggt gaggctctga aagtggtaga agggaattct ttcctagagt tcagctgccc
    13081 gctgtcctgc tcctcagggc aaatgctgtg agatctgcat ttagcctgtc tgtgctgatt
    13141 gtggttctgc cccttcctgg ctgtgtgacc tcagacaagt cacccaccct ctctgggcca
    13201 gtttcctcat ctggaaaagg ggacagtgcc caccacattg ggctgtttgt gtccatggag
    13261 tgcctgacaa tacccagcac acacgagaca tcagtacagg gtggttcctt ccctccttag
    13321 ccccacctgt tcccaggtag aaaccaatac cggcagggaa ccttctcaag gctaggggcc
    13381 ttctgaaagc agcagcactt ttcctccttc aaagaccttg ccttctagaa acccattgct
    13441 cattcctttc tccatgtacc aaaaaatcaa ttaaagtggc taaagacaga cgtcaccctc
    13501 ccctactcac gcagccattc tgatcctcca cgctggtgac aggctatgtg gcaggagggt
    13561 ctctacctta tctcagaatg aaggcatggc tggggtctgg ctgtctcctg gtggccggaa
    13621 ggagacagac ggcaaaggag aagctgcctg tctctgcaca ggtccatgtc cctgaggaaa
    13681 gccaacgtca cagagaaatg atgaccactt tctcaaacct ggcttcggat ttgcacgttg
    13741 gctgccaaag ctgatcagca gcgggctttg tgaagatgcc tggtctacca cgtgcctcca
    13801 gctggtcacg cccaagactc cctgagccct ctggaagggc agcacttgcc cagtgcctcc
    13861 ctccaggtcc tgccacatcc aagaaccacc tggactatta tttacttagt attttaaacc
    13921 aatgtacttt ttaaactcca attttttaat aagatcattt atgtcaccat ataacaccca
    13981 aagcagtaga atttgtcata cacagaaggc aatgctaaaa atacaatgaa aatggaacca
    14041 ggaagtctag cttgataccc ttggcctgta taactgagcc ttgtgccagt taaaagggca
    14101 aagcagtagg tgctcagggg gtgtcggggc cctgagagct gatctgatcc gctgctgcgt
    14161 attcactacc gccctgggac gcctccagca gaccacctca ctgggggaaa catcaggaca
    14221 gcgtggccag gagcccaatg ctgccacctc atagatgggt atctgagatg agtcatcgaa
    14281 cttctgcaag cctcagtttc ctccctggtc taatggaacc ctccttggcg gcttcacagg
    14341 gtgatgcttg gggcaggtga tggagatgtg ggagaggcag ttatttttaa ccacccagcc
    14401 aagccccttg ccaggaggga ctcccagaaa tgaagcctta cccttgaggg agttccccgc
    14461 cactccaagc ttggggcctg ggatggcagc tgtgagggca ccagcaccat ctggggactc
    14521 gctgggtacc aattatcacc gcccttgggc tacttcaaag gctgcccaca cagacacacc
    14581 ctccttggta accagtcctc aggaggaagg gcacccaagg aaagggggaa ggcttcctgg
    14641 gctagagccc cttcagggtc tgacacgcca ttgacactga ccacgtcatt cattaagcaa
    14701 gcaccaacta tacatcattc actatcccaa tctaatttgc acaagccctt aggcaggtgc
    14761 tactattatc cctgttttac agagaaggaa accgaggctt aggagatgaa gtctgaggtg
    14821 ttggtggagc tgggatttaa accaaaatat gtccaactgc aaagcatgta agtaacaatt
    14881 ttagagggta tacggaggtg accctaagta acaaggaatc acatatagtg agcaagcaat
    14941 ttgcttttca gtttttggtc aatccttatg attatttaga ggagaaagtt cagtttggtg
    15001 ctggtatatc ttatgtttat cacccgacag ttgttaatct ctttttaaca aagaatacag
    15061 gccaaggccc tgtgacttta gctggctttg gtatttggcc aaaagttaat gactttggca
    15121 gttagtgttt ttatccatgc caagcgatga tgattttctc tttagtgaca gacatttttt
    15181 aaaaaataaa ttcacataaa aaagtagttt tacagatgaa gcactaaaac tagtgcattt
    15241 catcttaaac tgcaaattat aaagggaata atagtaactt gacagtggag agacctggca
    15301 gacaccacct tcaccaactg atcaaagtta acatcgccag aaaggggaca gatggcatgt
    15361 gcctctcgat aagatgcact gaagacacac actcacttct gcaatattcc tgccaagaat
    15421 gcctcatctg aatctaatct cgagtataac catcagacaa acccaaattg agagacagtt
    15481 tacaaaacac cagccttgta ctctgcttaa tatgtcaatg tcacaagaga gaaagacaga
    15541 ctgaagagct gatccagact gaagaaggct cgagattaat gcaaaagctg atctgggatt
    15601 gcatcttgga cctcaactct ccccttttta ttgttaaggg acactactgg gacaattttt
    15661 tttttttttc gttttgagac agggtctcgc tcagtcaccc aggctggagt gcagtggtgg
    15721 aataataact cactgcagcc ttgaactccc ggactcaagc aatcctcctg cctgagcctt
    15781 ccgagtaact gggactatgg gcgtgtacca caacacctcg ctattttttt tttcctactt
    15841 tttgtagaga cggggtctca ctatgttgcc caggctggtt tcaaactcaa gtgatccttc
    15901 cacctcagcc tctataaaat ttgaataaag ttgtagatga gattggtcat aggattgtat
    15961 agtgtatcaa tattagattt gctgattttg acaaccctac tgtggttatg caaatttgtc
    16021 cttgttctaa ggaaataaat actgaattat ttaggagtaa a
//
