LOCUS       NM_001014342            9124 bp    mRNA    linear   PRI 02-APR-2024
DEFINITION  Homo sapiens filaggrin 2 (FLG2), mRNA.
ACCESSION   NM_001014342 XM_371313
VERSION     NM_001014342.3
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 9124)
  AUTHORS   Vergouwen,D.P.C., Ten Berge,J.C., Guzel,C., van den Bosch,T.P.P.,
            Verdijk,R.M., Rothova,A., Luider,T.M. and Schreurs,M.W.J.
  TITLE     Scleral Proteome in Noninfectious Scleritis Unravels Upregulation
            of Filaggrin-2 and Signs of Neovascularization
  JOURNAL   Invest Ophthalmol Vis Sci 64 (3), 27 (2023)
   PUBMED   36930145
  REMARK    GeneRIF: Scleral Proteome in Noninfectious Scleritis Unravels
            Upregulation of Filaggrin-2 and Signs of Neovascularization.
REFERENCE   2  (bases 1 to 9124)
  AUTHORS   Berna,R., Mitra,N., Hoffstad,O., Wubbenhorst,B., Nathanson,K.L. and
            Margolis,D.J.
  TITLE     Uncommon variants in FLG2 and TCHHL1 are associated with remission
            of atopic dermatitis in a large longitudinal US cohort
  JOURNAL   Arch Dermatol Res 314 (10), 953-959 (2022)
   PUBMED   34984527
  REMARK    GeneRIF: Uncommon variants in FLG2 and TCHHL1 are associated with
            remission of atopic dermatitis in a large longitudinal US cohort.
REFERENCE   3  (bases 1 to 9124)
  AUTHORS   Darbord,D., Hickman,G., Pironon,N., Barbieux,C.,
            Bonnet-des-Claustres,M., Titeux,M., Miskinyte,S., Cordoliani,F.,
            Vignon-Pennamen,M.D., Amode,R., Hovnanian,A. and Bourrat,E.
  TITLE     Dystrophic epidermolysis bullosa pruriginosa: a new case series of
            a rare phenotype unveils skewed Th2 immunity
  JOURNAL   J Eur Acad Dermatol Venereol 36 (1), 133-143 (2022)
   PUBMED   34543471
  REMARK    GeneRIF: Dystrophic epidermolysis bullosa pruriginosa: a new case
            series of a rare phenotype unveils skewed Th2 immunity.
REFERENCE   4  (bases 1 to 9124)
  AUTHORS   Donovan,M., Salamito,M., Thomas-Collignon,A., Simonetti,L.,
            Desbouis,S., Rain,J.C., Formstecher,E. and Bernard,D.
  TITLE     Filaggrin and filaggrin 2 processing are linked together through
            skin aspartic acid protease activation
  JOURNAL   PLoS One 15 (5), e0232679 (2020)
   PUBMED   32437351
  REMARK    GeneRIF: Filaggrin and filaggrin 2 processing are linked together
            through skin aspartic acid protease activation.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 9124)
  AUTHORS   de Carvalho-Siqueira,G.Q., Ananina,G., de Souza,B.B., Borges,M.G.,
            Ito,M.T., da Silva-Costa,S.M., de Farias Domingos,I., Falcao,D.A.,
            Lopes-Cendes,I., Bezerra,M.A.C., da Silva Araujo,A.,
            Lucena-Araujo,A.R., de Souza Goncalves,M., Saad,S.T.O., Costa,F.F.
            and de Melo,M.B.
  TITLE     Whole-exome sequencing indicates FLG2 variant associated with leg
            ulcers in Brazilian sickle cell anemia patients
  JOURNAL   Exp Biol Med (Maywood) 244 (11), 932-939 (2019)
   PUBMED   31079484
  REMARK    GeneRIF: In a stop codon variant (rs12568784 G/T) in the FLG2 gene.
REFERENCE   6  (bases 1 to 9124)
  AUTHORS   Hansmann,B., Schroder,J.M. and Gerstel,U.
  TITLE     Skin-Derived C-Terminal Filaggrin-2 Fragments Are Pseudomonas
            aeruginosa-Directed Antimicrobials Targeting Bacterial Replication
  JOURNAL   PLoS Pathog 11 (9), e1005159 (2015)
   PUBMED   26371476
  REMARK    GeneRIF: Data suggest that innate immunity of skin involves FLG2,
            which is expressed in high abundance in upper epidermis/eccrine
            sweat glands; C-terminal peptide fragments of FLG2 exhibit
            antimicrobial functions against replication of Pseudomonas
            aeruginosa and E. coli.
            Publication Status: Online-Only
REFERENCE   7  (bases 1 to 9124)
  AUTHORS   Pellerin,L., Henry,J., Hsu,C.Y., Balica,S., Jean-Decoster,C.,
            Mechin,M.C., Hansmann,B., Rodriguez,E., Weindinger,S.,
            Schmitt,A.M., Serre,G., Paul,C. and Simon,M.
  TITLE     Defects of filaggrin-like proteins in both lesional and nonlesional
            atopic skin
  JOURNAL   J Allergy Clin Immunol 131 (4), 1094-1102 (2013)
   PUBMED   23403047
REFERENCE   8  (bases 1 to 9124)
  AUTHORS   Hsu,C.Y., Henry,J., Raymond,A.A., Mechin,M.C., Pendaries,V.,
            Nassar,D., Hansmann,B., Balica,S., Burlet-Schiltz,O., Schmitt,A.M.,
            Takahara,H., Paul,C., Serre,G. and Simon,M.
  TITLE     Deimination of human filaggrin-2 promotes its proteolysis by
            calpain 1
  JOURNAL   J Biol Chem 286 (26), 23222-23233 (2011)
   PUBMED   21531719
  REMARK    GeneRIF: calpain 1 is essential for the proteolytic processing of
            FLG2 and that deimination accelerates this process.
REFERENCE   9  (bases 1 to 9124)
  AUTHORS   Stemmler,S., Nothnagel,M., Parwez,Q., Petrasch-Parwez,E.,
            Epplen,J.T. and Hoffjan,S.
  TITLE     Variation in genes of the epidermal differentiation complex in
            German atopic dermatitis patients
  JOURNAL   Int J Immunogenet 36 (4), 217-222 (2009)
   PUBMED   19601998
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   10 (bases 1 to 9124)
  AUTHORS   Wu,Z., Hansmann,B., Meyer-Hoffert,U., Glaser,R. and Schroder,J.M.
  TITLE     Molecular identification and expression analysis of filaggrin-2, a
            member of the S100 fused-type protein family
  JOURNAL   PLoS One 4 (4), e5227 (2009)
   PUBMED   19384417
  REMARK    GeneRIF: FLG2 and filaggrin may have overlapping and perhaps
            synergistic roles in the formation of the epidermal barrier,
            protecting the skin from environmental insults and the escape of
            moisture by offering precursors of natural moisturizing factors
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AY827490.1, AL356504.5,
            BX095286.1 and BC108269.1.
            
            On May 17, 2019 this sequence version replaced NM_001014342.2.
            
            Summary: The filaggrin-like protein encoded by this gene is
            upregulated by calcium, proteolyzed by calpain 1, and is involved
            in epithelial homeostasis. The encoded protein is required for
            proper cornification in skin, with defects in this gene being
            associated with skin diseases. This protein also has a function in
            skin barrier protection. In fact, in addition to providing a
            physical barrier, C-terminal fragments of this protein display
            antimicrobial activity against P. aeruginosa and E. coli. [provided
            by RefSeq, Jul 2020].
            
            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 :: BX095286.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match                 :: ENST00000388718.5/
                                                  ENSP00000373370.4
            Protein has antimicrobial activity :: PMID: 26371476
            RefSeq Select criteria             :: based on single
                                                  protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-16                AY827490.1         1-16
            17-17               AL356504.5         77666-77666         c
            18-37               AY827490.1         18-37
            38-250              BX095286.1         1-213
            251-8875            AY827490.1         252-8876
            8876-9122           BC108269.1         1327-1573
            9123-9124           AL356504.5         66411-66412         c
FEATURES             Location/Qualifiers
     source          1..9124
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q21.3"
     gene            1..9124
                     /gene="FLG2"
                     /gene_synonym="IFPS; PSS6"
                     /note="filaggrin 2"
                     /db_xref="GeneID:388698"
                     /db_xref="HGNC:HGNC:33276"
                     /db_xref="MIM:616284"
     exon            1..51
                     /gene="FLG2"
                     /gene_synonym="IFPS; PSS6"
                     /inference="alignment:Splign:2.1.0"
     exon            52..211
                     /gene="FLG2"
                     /gene_synonym="IFPS; PSS6"
                     /inference="alignment:Splign:2.1.0"
     CDS             74..7249
                     /gene="FLG2"
                     /gene_synonym="IFPS; PSS6"
                     /note="ifapsoriasin; intermediate filament-associated and
                     psoriasis susceptibility protein; filaggrin family member
                     2"
                     /codon_start=1
                     /product="filaggrin-2"
                     /protein_id="NP_001014364.1"
                     /db_xref="CCDS:CCDS30861.1"
                     /db_xref="GeneID:388698"
                     /db_xref="HGNC:HGNC:33276"
                     /db_xref="MIM:616284"
                     /translation="MTDLLRSVVTVIDVFYKYTKQDGECGTLSKGELKELLEKELHPV
                     LKNPDDPDTVDVIMHMLDRDHDRRLDFTEFLLMIFKLTMACNKVLSKEYCKASGSKKH
                     RRGHRHQEEESETEEDEEDTPGHKSGYRHSSWSEGEEHGYSSGHSRGTVKCRHGSNSR
                     RLGRQGNLSSSGNQEGSQKRYHRSSCGHSWSGGKDRHGSSSVELRERINKSHISPSRE
                     SGEEYESGSGSNSWERKGHGGLSCGLETSGHESNSTQSRIREQKLGSSCSGSGDSGRR
                     SHACGYSNSSGCGRPQNASSSCQSHRFGGQGNQFSYIQSGCQSGIKGGQGHGCVSGGQ
                     PSGCGQPESNPCSQSYSQRGYGARENGQPQNCGGQWRTGSSQSSCCGQYGSGGSQSCS
                     NGQHEYGSCGRFSNSSSSNEFSKCDQYGSGSSQSTSFEQHGTGLSQSSGFEQHVCGSG
                     QTCGQHESTSSQSLGYDQHGSSSGKTSGFGQHGSGSGQSSGFGQCGSGSGQSSGFGQH
                     GSVSGQSSGFGQHGSVSGQSSGFGQHESRSRQSSYGQHGSGSSQSSGYGQYGSRETSG
                     FGQHGLGSGQSTGFGQYGSGSGQSSGFGQHGSGSGQSSGFGQHESRSGQSSYGQHSSG
                     SSQSSGYGQHGSRQTSGFGQHGSGSSQSTGFGQYGSGSGQSSGFGQHVSGSGQSSGFG
                     QHESRSGHSSYGQHGFGSSQSSGYGQHGSSSGQTSGFGQHELSSGQSSSFGQHGSGSG
                     QSSGFGQHGSGSGQSSGFGQHESRSGQSSYGQHSSGSSQSSGYGQHGSRQTSGFGQHG
                     SGSSQSTGFGQYGSGSGQSAGFGQHGSGSGQSSGFGQHESRSHQSSYGQHGSGSSQSS
                     GYGQHGSSSGQTSGFGQHRSSSGQYSGFGQHGSGSGQSSGFGQHGTGSGQYSGFGQHE
                     SRSHQSSYGQHGSGSSQSSGYGQHGSSSGQTFGFGQHRSGSGQSSGFGQHGSGSGQSS
                     GFGQHESGSGKSSGFGQHESRSSQSNYGQHGSGSSQSSGYGQHGSSSGQTTGFGQHRS
                     SSGQYSGFGQHGSGSDQSSGFGQHGTGSGQSSGFGQYESRSRQSSYGQHGSGSSQSSG
                     YGQHGSNSGQTSGFGQHRPGSGQSSGFGQYGSGSGQSSGFGQHGSGTGKSSGFAQHEY
                     RSGQSSYGQHGTGSSQSSGCGQHESGSGPTTSFGQHVSGSDNFSSSGQHISDSGQSTG
                     FGQYGSGSGQSTGLGQGESQQVESGSTVHGRQETTHGQTINTTRHSQSGQGQSTQTGS
                     RVTRRRRSSQSENSDSEVHSKVSHRHSEHIHTQAGSHYPKSGSTVRRRQGTTHGQRGD
                     TTRHGHSGHGQSTQTGSRTSGRQRFSHSDATDSEVHSGVSHRPHSQEQTHSQAGSQHG
                     ESESTVHERHETTYGQTGEATGHGHSGHGQSTQRGSRTTGRRGSGHSESSDSEVHSGG
                     SHRPQSQEQTHGQAGSQHGESGSTVHGRHGTTHGQTGDTTRHAHYHHGKSTQRGSSTT
                     GRRGSGHSESSDSEVHSGGSHTHSGHTHGQSGSQHGESESIIHDRHRITHGQTGDTTR
                     HSYSGHEQTTQTGSRTTGRQRTSHSESTDSEVHSGGSHRPHSREHTYGQAGSQHEEPE
                     FTVHERHGTTHGQIGDTTGHSHSGHGQSTQRGSRTTGRQRSSHSESSDSEVHSGVSHT
                     HTGHTHGQAGSQHGQSESIVPERHGTTHGQTGDTTRHAHYHHGLTTQTGSRTTGRRGS
                     GHSEYSDSEGYSGVSHTHSGHTHGQARSQHGESESIVHERHGTIHGQTGDTTRHAHSG
                     HGQSTQTGSRTTGRRSSGHSEYSDSEGHSGFSQRPHSRGHTHGQAGSQHGESESIVDE
                     RHGTTHGQTGDTSGHSQSGHGQSTQSGSSTTGRRRSGHSESSDSEVHSGGSHTHSGHT
                     HSQARSQHGESESTVHKRHQTTHGQTGDTTEHGHPSHGQTIQTGSRTTGRRGSGHSEY
                     SDSEGPSGVSHTHSGHTHGQAGSHYPESGSSVHERHGTTHGQTADTTRHGHSGHGQST
                     QRGSRTTGRRASGHSEYSDSEGHSGVSHTHSGHAHGQAGSQHGESGSSVHERHGTTHG
                     QTGDTTRHAHSGHGQSTQRGSRTAGRRGSGHSESSDSEVHSGVSHTHSGHTYGQARSQ
                     HGESGSAIHGRQGTIHGQTGDTTRHGQSGHGQSTQTGSRTTGRQRSSHSESSDSEVHS
                     EASPTHSGHTHSQAGSRHGQSGSSGHGRQGTTHGQTGDTTRHAHYGYGQSTQRGSRTT
                     GRRGSGHSESSDSEVHSWGSHTHSGHIQGQAGSQQRQPGSTVHGRLETTHGQTGDTTR
                     HGHSGYGQSTQTGSRSSRASHFQSHSSERQRHGSSQVWKHGSYGPAEYDYGHTGYGPS
                     GGSRKSISNSHLSWSTDSTANKQLSRH"
     exon            212..9124
                     /gene="FLG2"
                     /gene_synonym="IFPS; PSS6"
                     /inference="alignment:Splign:2.1.0"
ORIGIN      
        1 accctgcaag ctgcatcagg ctttatccta cttgttcctt tggtgaacca ggttcactta
       61 aacttgcaaa aagatgaccg acctcttgag aagtgttgtc accgtaattg atgttttcta
      121 caaatacacc aagcaagatg gggagtgtgg cacactgagc aagggtgaac taaaggaact
      181 tctggagaaa gagcttcatc cagttctgaa gaacccagat gatccagaca cagtggatgt
      241 catcatgcat atgctggatc gagatcatga cagaagattg gactttactg agtttctttt
      301 gatgatattc aagctgacta tggcctgcaa caaggtcctc agcaaagaat actgcaaagc
      361 ttcagggtca aagaagcata ggcgtggtca ccgacaccaa gaagaagaaa gtgaaacaga
      421 agaggatgaa gaggatacac caggacataa atcaggttac agacattcaa gttggagtga
      481 gggagaggag catggatata gttctgggca ctcaagggga actgtgaaat gtagacatgg
      541 gtccaactcc aggaggctag gaagacaagg taatttatcc agctctggga accaagaggg
      601 atctcagaaa agataccaca ggtccagctg tggtcattca tggagtggtg gcaaagacag
      661 acatggttcc agctctgtag aactgagaga aagaataaac aagtcacaca ttagcccttc
      721 tagggaatct ggggaggagt atgaatctgg atctggatca aacagttggg aaaggaaagg
      781 tcatggtggt ctgtcatgtg gattggagac tagtgggcat gaatcaaact ctactcagtc
      841 aagaattaga gaacaaaagc ttgggtctag ctgttcaggt tcaggagaca gtgggaggcg
      901 aagtcatgca tgtggttata gcaattcaag tgggtgtgga aggccacaaa atgcttcaag
      961 ttcttgtcag tcacatagat ttggagggca aggaaatcaa tttagctata ttcagtcagg
     1021 ctgtcagtca ggaattaagg gaggacaagg ccatggctgt gtctcaggag gtcagccctc
     1081 tggatgtggt caacctgagt ctaacccctg tagtcagtcc tatagtcaga gaggatatgg
     1141 agctagagaa aatggtcaac cacagaactg tggaggacaa tggagaacag gctcaagtca
     1201 gtcctcttgc tgtggacaat atgggtctgg aggtagccag tcttgtagta atggtcaaca
     1261 tgaatatggt tcctgtggcc gcttttcaaa ctcttctagt tcaaatgaat tttccaaatg
     1321 tgatcaatat gggtctggtt caagtcagtc tactagcttt gaacaacatg gaacaggctt
     1381 gagtcagtcc tctgggttcg aacaacatgt atgtggctca ggtcaaactt gtggccagca
     1441 tgagtctaca tcaagtcaat ccttgggcta tgaccagcat gggtctagct caggtaagac
     1501 atctggcttt ggacaacatg ggtctggctc aggtcagtcc tctggctttg gacaatgtgg
     1561 gtcaggctca ggtcagtcct ctggctttgg acagcatggg tctgtctcag gacaatcctc
     1621 tggttttgga cagcatgggt ctgtctcagg acaatcctct ggttttggac aacatgagtc
     1681 tagatcacgt cagtctagct atggccaaca tggttctggc tcaagtcaat catctggcta
     1741 tggccaatat gggtctagag agacatctgg ctttggacaa catgggttgg gctcaggtca
     1801 atccactggc tttggccaat atggatcggg ctcaggtcag tcctctggct ttggacaaca
     1861 tgggtctggc tcaggacaat cctctggctt tggacaacat gagtctagat caggtcagtc
     1921 tagttatggc caacacagtt ctggctcaag tcagtcatct ggctatggcc aacatgggtc
     1981 tagacagaca tctggctttg gacaacatgg gtcaggctca agtcaatcca ctggctttgg
     2041 ccaatatgga tcaggctcag gtcagtcctc tggctttgga caacatgttt ctggctcagg
     2101 acaatcctct ggttttggac aacatgagtc tagatcaggt cattctagct atggccaaca
     2161 tggttttggc tcaagtcaat catctggcta tggtcaacat gggtcaagtt caggacagac
     2221 atctggattt ggacaacacg agttaagctc aggtcagtct tccagctttg gccaacatgg
     2281 atcaggctca ggtcagtcct ctggctttgg acaacatggg tctggctcag gacaatcctc
     2341 tggctttgga caacatgagt ctagatcagg tcagtctagc tatggccaac acagttctgg
     2401 ctcaagtcag tcatctggct atggccaaca tgggtctaga cagacatctg gctttggaca
     2461 acatgggtca ggctcaagtc aatccactgg ctttggccaa tatggatcag gctcaggtca
     2521 gtccgctggc tttggacaac atgggtctgg ctcaggacaa tcctctggct ttggacagca
     2581 tgagtctaga tcacatcagt ccagctatgg ccaacatggt tctggctcaa gtcaatcatc
     2641 tggctatggt caacatgggt caagttcggg acagacatct ggctttggac aacacaggtc
     2701 aagctcaggt caatactctg gctttggaca acatggatca ggctcaggtc agtccagtgg
     2761 ctttggacaa catgggactg gctcaggaca atactctggt tttggacaac atgagtctag
     2821 atcacatcag tctagctatg gccaacatgg ttctggctca agtcagtcat ctggctatgg
     2881 tcaacatggg tcaagttcag gacagacttt tggatttgga caacacaggt caggctcagg
     2941 tcaatcctct ggctttggcc aacatggatc aggctcaggt cagtcctctg gctttggaca
     3001 acatgagtca ggctcaggaa aatcctctgg ctttggacag catgagtcta gatcaagtca
     3061 gtctaattat ggccaacatg gttctggctc aagtcagtca tctggctatg gtcaacatgg
     3121 gtctagttca ggacagacaa ctggctttgg acaacacagg tcaagctcag gccaatactc
     3181 aggctttgga caacatggat caggctcaga tcagtcctct ggctttggac aacatgggac
     3241 tggttcagga caatcctctg gttttggaca atatgagtct agatcacgtc agtctagcta
     3301 tggccaacat ggttctggct caagtcaatc atctggctat ggtcaacatg ggtcaaattc
     3361 aggacagaca tctggatttg gacaacacag gccaggctca ggtcagtcct ctggctttgg
     3421 ccaatatgga tcgggctcag gtcagtcttc tggctttgga caacatgggt caggcacagg
     3481 taaatcctct ggctttgcac agcatgagta cagatcaggt cagtctagct atggccaaca
     3541 tggtactggc tccagtcaat catctggctg tggccaacat gagtctggct caggtccaac
     3601 cacaagtttt ggacagcatg tgtctggctc agacaatttc tctagttctg gacaacatat
     3661 atctgactca ggtcagtcca ctggatttgg ccaatatggt tcaggctcag gtcaatcaac
     3721 tggcttgggc cagggtgaat ctcaacaagt agagtcagga tccacagttc atgggagaca
     3781 ggaaactact catggtcaga caataaatac cactagacat agccagtctg gtcaaggaca
     3841 atccacacag acagggtcca gggtaactag aagacgaaga tctagccaaa gtgagaacag
     3901 tgacagtgaa gtgcactcaa aggtctcaca cagacattca gaacacattc acacacaagc
     3961 tggatctcac tacccaaagt caggatccac agttcgcaga agacaaggaa ctactcatgg
     4021 acagagagga gataccacta gacatggcca ttctggtcat ggacagtcta cacagacagg
     4081 ttccagaaca tctggaagac agagatttag ccacagtgat gccactgaca gtgaagtgca
     4141 ctcaggggtc tcacatagac cacactcaca agaacaaact cacagccaag ctggatctca
     4201 acatggagag tcagaatcca cagttcatga gagacatgaa actacttatg gacagacagg
     4261 agaggccact ggacatggcc actctggtca tggacagtcc acacagagag ggtccaggac
     4321 aactggaaga aggggatctg gccatagtga gtccagtgac agtgaagtgc actcaggggg
     4381 ctcacacaga ccacaatcac aagaacaaac tcatggccaa gccggatctc aacatggaga
     4441 gtcaggatcc acagttcatg ggagacacgg aactactcat ggacagacag gagataccac
     4501 tagacatgcc cactatcatc atggaaaatc cacacagaga gggtccagta caactggaag
     4561 aaggggatct ggccacagtg agtccagtga cagtgaagtg cactcagggg gctcgcacac
     4621 acattcagga cacactcacg gccaaagtgg atctcaacat ggagagtcag aatccataat
     4681 tcatgacaga cacagaatta ctcatggaca gacaggagat accactagac attcctactc
     4741 tggtcatgaa caaaccacac agacagggtc caggacaact ggaagacaga gaactagcca
     4801 cagtgagtcc actgacagtg aagtgcactc agggggctca cacagaccac actcacgaga
     4861 acacacttac ggccaagccg gatctcaaca tgaagagcca gaattcacag ttcatgagag
     4921 acacggaact actcatggac agataggaga taccactgga cattcccact ctggtcatgg
     4981 acagtccaca cagagagggt ccaggacaac tggaagacag agatctagcc acagtgagtc
     5041 cagtgacagt gaagtgcact caggggtctc acacacacat acaggacaca ctcatggtca
     5101 agctggatct caacatggac agtcagaatc catagttcct gagagacatg gaactactca
     5161 tggacagaca ggagatacca ctagacatgc ccactatcat catggattaa ccacacagac
     5221 agggtccagg actactggaa gaaggggatc tggccacagt gagtacagtg acagtgaagg
     5281 gtactcagga gtctcacata cacattcagg acacactcat ggccaagcca gatctcaaca
     5341 tggagagtca gaatccatag ttcatgagag acatggaact atacatggac agacaggcga
     5401 taccaccaga catgcccact ctggtcatgg acagtccaca cagacagggt ccaggaccac
     5461 tggaagaagg tcatctggcc acagtgagta cagtgacagt gaagggcact cagggttctc
     5521 acaaagacca cactcacgag gacacactca cggccaggct ggatctcaac atggagagtc
     5581 agaatccata gttgacgaga gacatggaac tactcatgga cagacaggag ataccagtgg
     5641 acattctcaa tctggtcatg gacagtccac acagtcagga tccagtacaa ctggaagaag
     5701 gagatctggc cacagtgagt ccagtgacag tgaagtgcac tcagggggct cacatacaca
     5761 ttcaggacac acacacagcc aagccaggtc tcaacatgga gagtcagaat ccacagttca
     5821 caagagacac caaactactc atggacagac aggagatacc actgaacatg gccaccctag
     5881 tcatggacaa accatacaga cagggtccag gacaactgga agaaggggat ctggccacag
     5941 tgagtacagt gacagtgaag ggccctcagg ggtctcacac acacattcag gacacactca
     6001 cggtcaagct ggatctcact atccagagtc aggatcctca gttcatgaga gacacggaac
     6061 tactcatgga caaacagcag ataccactag acatggccac tctggtcatg gacagtccac
     6121 acagagaggg tccaggacaa ctggaagaag ggcatctggc cacagtgagt acagtgacag
     6181 tgaagggcac tcaggggtct cacacacaca ttcaggacac gctcatggcc aagccggatc
     6241 tcaacatgga gagtcaggat cctcagttca tgagagacac ggaactactc atggacagac
     6301 aggagatacc actagacatg ctcactctgg tcatggacag tccacacaga gagggtcaag
     6361 gacagctgga agaaggggat ctggccacag tgagtccagt gacagtgaag tgcactcagg
     6421 ggtctcacac acacattcag gacacactta tggccaagcc agatctcaac atggagagtc
     6481 aggatctgcc attcacggga gacagggaac tatacatgga cagacaggag ataccactag
     6541 acatggccag tctggtcatg gacagtccac acagacaggt tccaggacaa ctggaagaca
     6601 aagatctagt cacagtgagt ccagtgatag tgaagtgcac tcagaggcct cacccacaca
     6661 ttcaggacac actcacagcc aagccggatc tcgacatgga cagtcaggat cctcaggtca
     6721 tgggagacag ggaactactc atggacagac aggagatacc actagacatg cccactatgg
     6781 ttatggacaa tccacacaga gagggtccag gacaactgga agaaggggat ctggccacag
     6841 tgagtccagt gacagtgaag tgcactcatg gggctcacac acacattcag gacacattca
     6901 gggccaagct ggatctcaac aaagacagcc aggatccaca gttcatggga gactggaaac
     6961 tactcatgga cagacaggag ataccactag acatggccat tctggttatg gacaatccac
     7021 acagacaggt tccagatcta gtagagcaag tcattttcag tcacatagta gtgaaaggca
     7081 aaggcatgga tcaagtcagg tttggaaaca tggcagctat ggacctgcag aatatgacta
     7141 tgggcacact gggtatgggc cttctggtgg cagcagaaaa agcatcagta attctcacct
     7201 ttcatggtca acagacagca ctgcaaacaa gcaactgtct agacattgac agttattttc
     7261 tagttctgac cttatagtat ccaaagcaac taaaagaaca ggaagacaca gtttaaatca
     7321 tgaacagtca atggtaagtt atgaacattc agttgattct cagtatcagt ctcgacctat
     7381 tattataaga agtcaggaat ctagtcatgg acattctata gtaactcata aacagtcaaa
     7441 caacacctat gttcaacctg gatataacac agccagaagg gagggatgta cacatagcca
     7501 gtcaaatgac caccttggat ttggccatgg acaatccata tcagttcatg gccattcaaa
     7561 atctagttca atcagaaaac aggaatccca tactgataac aaaaagcatt cagaagattg
     7621 ggagaaagac actcatgagc aattaggatc taggcatggg aagttagagt tcaatacaat
     7681 aggtatacat ggatctagcc agcaacattt cggagataca acttttcatg ggcaggtaag
     7741 atccagcaca ggttttgcca gataggtatt aagtcatggg ccatcaagag atgcctaggg
     7801 tcagtctgga ttcagtacca atgaaagaca agtatacagc catggccaat caaatgatag
     7861 ttatgagtag tcaaatgaca gcaaaagtca aagatacatt ttcagtcact ttcttgacag
     7921 ccaagaccct gcaggaattg aagagtatag gtatagatat tcatcaagca gtgcaaccat
     7981 atgcagtggg ggagacaaag gcaagagtca gagtcaagtc tgtcaggagg tatcagaata
     8041 tacggtgagg atgtgggcaa aaaacaaaga ggctctgagg ccagcggtta ccatacaaag
     8101 gaaagaacag gctctggttc cttctgctta gatagcaaca ccccactcta tgaatatgtc
     8161 caagaacaaa ggagttatta ctttgaataa gaagccaaca taaactagcc caagataaga
     8221 actaacccag agaagaaatg agacacatac atgaaattaa ggtatttaac atgatctcct
     8281 cttttggtag taagggtata tgtctgttct ttcattttaa ctatagttct gtactatatt
     8341 acttttgttt ggtgccaggt gtttttgtaa ggctccacat tcattgaact ccttggttag
     8401 aaaatagtga atgaggccgg gcgcggtggc tcacgcctgt aatcccagca ctttgggagg
     8461 ccaagatggg tggatcacga agtcaggagt tcgagaccag cctggccaac atagtgaaat
     8521 cccgtctcta ctaaaaatac aaaaattagc tgggtgcagt agcgggcacc tgtaatccta
     8581 gctactcagg aggctgaggc aggagaattg gttgaacccg ggaggcagag gttgcagtga
     8641 gccgagatcg caccactgca ctccagcctg ggtgactgag caagactcca ccttgaaaaa
     8701 aagaaagaaa gaaaatagtg aatggaagaa aaagataaac accatttggg gctatattca
     8761 gaactatata ataaagagag atttgtgtgg ttgggaataa aattaggttt taaaaaaatt
     8821 tccgaatttc aaaatttgga ttttccagat tttgttttaa ttaattattg acaaacctat
     8881 ccaaggagct aaatgacgtg gtttaggagc caaaacgtct ctagaaacat tataacacat
     8941 cccatcctga acaaagaatg ttgtcatagt ttcccacatg aatattcaga atatttgcat
     9001 ctttttgtgt cactactgga attctgtaca attatattta aatttattgt catggccttc
     9061 tggatatagg atccagaaaa ttgtacttca taaaaattgg caataaacat ttcatcaagt
     9121 tata
//
