LOCUS       NM_002016              12793 bp    mRNA    linear   PRI 10-FEB-2025
DEFINITION  Homo sapiens filaggrin (FLG), mRNA.
ACCESSION   NM_002016 XM_048104 XM_378901
VERSION     NM_002016.2
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 12793)
  AUTHORS   Hemida,A.S., Hammam,M.A., Swilam,A.A. and Shehata,W.A.
  TITLE     Evaluation of OVOL1 and Filaggrin immunohistochemical expression
            and clinical relevance in psoriasis
  JOURNAL   Diagn Pathol 19 (1), 84 (2024)
   PUBMED   38907248
  REMARK    GeneRIF: Evaluation of OVOL1 and Filaggrin immunohistochemical
            expression and clinical relevance in psoriasis.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 12793)
  AUTHORS   Lo Piccolo,L., Wongkummool,W., Jantaree,P., Daroontum,T.,
            Chaowattanapanit,S., Choonhakarn,C., Amornpinyo,W., Chaiwarith,R.,
            Kiratikanon,S., Rujiwetpongstorn,R., Tovanabutra,N.,
            Chiewchanvit,S., Ngamphiw,C., Intachai,W., Kantaputra,P. and
            Chuamanochan,M.
  TITLE     Rare Filaggrin Variants Are Associated with Pustular Skin Diseases
            in Asians
  JOURNAL   Int J Mol Sci 25 (12), 6466 (2024)
   PUBMED   38928170
  REMARK    GeneRIF: Rare Filaggrin Variants Are Associated with Pustular Skin
            Diseases in Asians.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 12793)
  AUTHORS   Alibardi,L.
  TITLE     Immunolabeling for filaggrin and acidic keratins in the granular
            layer of mammalian epidermis indicates that an acidic-basic
            interaction is involved in cornification
  JOURNAL   Tissue Cell 88, 102397 (2024)
   PUBMED   38677234
  REMARK    GeneRIF: Immunolabeling for filaggrin and acidic keratins in the
            granular layer of mammalian epidermis indicates that an
            acidic-basic interaction is involved in cornification.
REFERENCE   4  (bases 1 to 12793)
  AUTHORS   Virolainen,S.J., Satish,L., Biagini,J.M., Chaib,H., Chang,W.C.,
            Dexheimer,P.J., Dixon,M.R., Dunn,K., Fletcher,D., Forney,C.,
            Granitto,M., Hestand,M.S., Hurd,M., Kauffman,K., Lawson,L.,
            Martin,L.J., Pena,L.D., Phelan,K.J., Shook,M., Weirauch,M.T.,
            Khurana Hershey,G.K. and Kottyan,L.C.
  TITLE     Filaggrin loss-of-function variants are associated with atopic
            dermatitis phenotypes in a diverse, early-life prospective cohort
  JOURNAL   JCI Insight 9 (9), e178258 (2024)
   PUBMED   38564302
  REMARK    GeneRIF: Filaggrin loss-of-function variants are associated with
            atopic dermatitis phenotypes in a diverse, early-life prospective
            cohort.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 12793)
  AUTHORS   Kojima,R., Miyake,K., Shinohara,R., Kushima,M., Yui,H., Otawa,S.,
            Horiuchi,S., Yokomichi,H., Akiyama,Y., Ooka,T. and Yamagata,Z.
  CONSRTM   Yamanashi Adjunct Study of the Japan Environment and Children's
            Study Group
  TITLE     Association between filaggrin gene mutations and the clinical
            features of molluscum contagiosum: The Yamanashi Adjunct Study of
            the Japan Environment and Children's Study
  JOURNAL   J Dermatol 51 (4), 484-490 (2024)
   PUBMED   38414183
  REMARK    GeneRIF: Association between filaggrin gene mutations and the
            clinical features of molluscum contagiosum: The Yamanashi Adjunct
            Study of the Japan Environment and Children's Study.
REFERENCE   6  (bases 1 to 12793)
  AUTHORS   Presland,R.B., Haydock,P.V., Fleckman,P., Nirunsuksiri,W. and
            Dale,B.A.
  TITLE     Characterization of the human epidermal profilaggrin gene. Genomic
            organization and identification of an S-100-like calcium binding
            domain at the amino terminus
  JOURNAL   J Biol Chem 267 (33), 23772-23781 (1992)
   PUBMED   1429717
REFERENCE   7  (bases 1 to 12793)
  AUTHORS   Gan,S.Q., McBride,O.W., Idler,W.W., Markova,N. and Steinert,P.M.
  TITLE     Organization, structure, and polymorphisms of the human
            profilaggrin gene
  JOURNAL   Biochemistry 30 (23), 5814 (1991)
   PUBMED   2043621
  REMARK    Correction to:[Biochemistry. 1990 Oct 9;29(40):9432-40. doi:
            10.1021/bi00492a018.. PMID: 2248957]
REFERENCE   8  (bases 1 to 12793)
  AUTHORS   Gan,S.Q., McBride,O.W., Idler,W.W., Markova,N. and Steinert,P.M.
  TITLE     Organization, structure, and polymorphisms of the human
            profilaggrin gene
  JOURNAL   Biochemistry 29 (40), 9432-9440 (1990)
   PUBMED   2248957
  REMARK    Erratum:[Biochemistry. 1991 Jun 11;30(23):5814.. PMID: 2043621]
REFERENCE   9  (bases 1 to 12793)
  AUTHORS   McKinley-Grant,L.J., Idler,W.W., Bernstein,I.A., Parry,D.A.,
            Cannizzaro,L., Croce,C.M., Huebner,K., Lessin,S.R. and
            Steinert,P.M.
  TITLE     Characterization of a cDNA clone encoding human filaggrin and
            localization of the gene to chromosome region 1q21
  JOURNAL   Proc Natl Acad Sci U S A 86 (13), 4848-4852 (1989)
   PUBMED   2740331
REFERENCE   10 (bases 1 to 12793)
  AUTHORS   Sybert,V.P., Dale,B.A. and Holbrook,K.A.
  TITLE     Ichthyosis vulgaris: identification of a defect in synthesis of
            filaggrin correlated with an absence of keratohyaline granules
  JOURNAL   J Invest Dermatol 84 (3), 191-194 (1985)
   PUBMED   2579164
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL356504.5.
            
            On Aug 31, 2019 this sequence version replaced NM_002016.1.
            
            Summary: The protein encoded by this gene is an intermediate
            filament-associated protein that aggregates keratin intermediate
            filaments in mammalian epidermis. It is initially synthesized as a
            polyprotein precursor, profilaggrin (consisting of multiple
            filaggrin units of 324 aa each), which is localized in keratohyalin
            granules, and is subsequently proteolytically processed into
            individual functional filaggrin molecules. Mutations in this gene
            are associated with ichthyosis vulgaris.[provided by RefSeq, Dec
            2009].
            
            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 :: L01090.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000368799.2/ ENSP00000357789.1
            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
            1-51                AL356504.5         42865-42915         c
            52-210              AL356504.5         32995-33153         c
            211-12793           AL356504.5         19841-32423         c
FEATURES             Location/Qualifiers
     source          1..12793
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q21.3"
     gene            1..12793
                     /gene="FLG"
                     /gene_synonym="ATOD2; FLG-1; FLG1"
                     /note="filaggrin"
                     /db_xref="GeneID:2312"
                     /db_xref="HGNC:HGNC:3748"
                     /db_xref="MIM:135940"
     exon            1..51
                     /gene="FLG"
                     /gene_synonym="ATOD2; FLG-1; FLG1"
                     /inference="alignment:Splign:2.1.0"
     exon            52..210
                     /gene="FLG"
                     /gene_synonym="ATOD2; FLG-1; FLG1"
                     /inference="alignment:Splign:2.1.0"
     CDS             73..12258
                     /gene="FLG"
                     /gene_synonym="ATOD2; FLG-1; FLG1"
                     /note="epidermal filaggrin"
                     /codon_start=1
                     /product="filaggrin"
                     /protein_id="NP_002007.1"
                     /db_xref="CCDS:CCDS30860.1"
                     /db_xref="GeneID:2312"
                     /db_xref="HGNC:HGNC:3748"
                     /db_xref="MIM:135940"
                     /translation="MSTLLENIFAIINLFKQYSKKDKNTDTLSKKELKELLEKEFRQI
                     LKNPDDPDMVDVFMDHLDIDHNKKIDFTEFLLMVFKLAQAYYESTRKENLPISGHKHR
                     KHSHHDKHEDNKQEENKENRKRPSSLERRNNRKGNKGRSKSPRETGGKRHESSSEKKE
                     RKGYSPTHREEEYGKNHHNSSKKEKNKTENTRLGDNRKRLSERLEEKEDNEEGVYDYE
                     NTGRMTQKWIQSGHIATYYTIQDEAYDTTDSLLEENKIYERSRSSDGKSSSQVNRSRH
                     ENTSQVPLQESRTRKRRGSRVSQDRDSEGHSEDSERHSGSASRNHHGSAWEQSRDGSR
                     HPRSHDEDRASHGHSADSSRQSGTRHAETSSRGQTASSHEQARSSPGERHGSGHQQSA
                     DSSRHSATGRGQASSAVSDRGHRGSSGSQASDSEGHSENSDTQSVSGHGKAGLRQQSH
                     QESTRGRSGERSGRSGSSLYQVSTHEQPDSAHGRTGTSTGGRQGSHHEQARDSSRHSA
                     SQEGQDTIRGHPGSSRGGRQGSHHEQSVNRSGHSGSHHSHTTSQGRSDASHGQSGSRS
                     ASRQTRNEEQSGDGTRHSGSRHHEASSQADSSRHSQVGQGQSSGPRTSRNQGSSVSQD
                     SDSQGHSEDSERWSGSASRNHHGSAQEQSRDGSRHPRSHHEDRAGHGHSADSSRKSGT
                     RHTQNSSSGQAASSHEQARSSAGERHGSRHQLQSADSSRHSGTGHGQASSAVRDSGHR
                     GSSGSQATDSEGHSEDSDTQSVSGHGQAGHHQQSHQESARDRSGERSRRSGSFLYQVS
                     THKQSESSHGWTGPSTGVRQGSHHEQARDNSRHSASQDGQDTIRGHPGSSRRGRQGSH
                     HEQSVDRSGHSGSHHSHTTSQGRSDASRGQSGSRSASRTTRNEEQSRDGSRHSGSRHH
                     EASSHADISRHSQAGQGQSEGSRTSRRQGSSVSQDSDSEGHSEDSERWSGSASRNHRG
                     SAQEQSRHGSRHPRSHHEDRAGHGHSADSSRQSGTPHAETSSGGQAASSHEQARSSPG
                     ERHGSRHQQSADSSRHSGIPRRQASSAVRDSGHWGSSGSQASDSEGHSEESDTQSVSG
                     HGQDGPHQQSHQESARDWSGGRSGRSGSFIYQVSTHEQSESAHGRTRTSTGRRQGSHH
                     EQARDSSRHSASQEGQDTIRAHPGSRRGGRQGSHHEQSVDRSGHSGSHHSHTTSQGRS
                     DASHGQSGSRSASRQTRKDKQSGDGSRHSGSRHHEAASWADSSRHSQVGQEQSSGSRT
                     SRHQGSSVSQDSDSERHSDDSERLSGSASRNHHGSSREQSRDGSRHPGFHQEDRASHG
                     HSADSSRQSGTHHTESSSHGQAVSSHEQARSSPGERHGSRHQQSADSSRHSGIGHRQA
                     SSAVRDSGHRGSSGSQVTNSEGHSEDSDTQSVSAHGQAGPHQQSHKESARGQSGESSG
                     RSRSFLYQVSSHEQSESTHGQTAPSTGGRQGSRHEQARNSSRHSASQDGQDTIRGHPG
                     SSRGGRQGSYHEQSVDRSGHSGYHHSHTTPQGRSDASHGQSGPRSASRQTRNEEQSGD
                     GSRHSGSRHHEPSTRAGSSRHSQVGQGESAGSKTSRRQGSSVSQDRDSEGHSEDSERR
                     SESASRNHYGSAREQSRHGSRNPRSHQEDRASHGHSAESSRQSGTRHAETSSGGQAAS
                     SQEQARSSPGERHGSRHQQSADSSTDSGTGRRQDSSVVGDSGNRGSSGSQASDSEGHS
                     EESDTQSVSAHGQAGPHQQSHQESTRGQSGERSGRSGSFLYQVSTHEQSESAHGRTGP
                     STGGRQRSRHEQARDSSRHSASQEGQDTIRGHPGSSRGGRQGSHYEQSVDSSGHSGSH
                     HSHTTSQERSDVSRGQSGSRSVSRQTRNEKQSGDGSRHSGSRHHEASSRADSSRHSQV
                     GQGQSSGPRTSRNQGSSVSQDSDSQGHSEDSERWSGSASRNHLGSAWEQSRDGSRHPG
                     SHHEDRAGHGHSADSSRQSGTRHTESSSRGQAASSHEQARSSAGERHGSHHQLQSADS
                     SRHSGIGHGQASSAVRDSGHRGYSGSQASDSEGHSEDSDTQSVSAQGKAGPHQQSHKE
                     SARGQSGESSGRSGSFLYQVSTHEQSESTHGQSAPSTGGRQGSHYDQAQDSSRHSASQ
                     EGQDTIRGHPGPSRGGRQGSHQEQSVDRSGHSGSHHSHTTSQGRSDASRGQSGSRSAS
                     RKTYDKEQSGDGSRHSGSHHHEASSWADSSRHSLVGQGQSSGPRTSRPRGSSVSQDSD
                     SEGHSEDSERRSGSASRNHHGSAQEQSRDGSRHPRSHHEDRAGHGHSAESSRQSGTHH
                     AENSSGGQAASSHEQARSSAGERHGSHHQQSADSSRHSGIGHGQASSAVRDSGHRGSS
                     GSQASDSEGHSEDSDTQSVSAHGQAGPHQQSHQESTRGRSAGRSGRSGSFLYQVSTHE
                     QSESAHGRTGTSTGGRQGSHHKQARDSSRHSTSQEGQDTIHGHPGSSSGGRQGSHYEQ
                     LVDRSGHSGSHHSHTTSQGRSDASHGHSGSRSASRQTRNDEQSGDGSRHSGSRHHEAS
                     SRADSSGHSQVGQGQSEGPRTSRNWGSSFSQDSDSQGHSEDSERWSGSASRNHHGSAQ
                     EQLRDGSRHPRSHQEDRAGHGHSADSSRQSGTRHTQTSSGGQAASSHEQARSSAGERH
                     GSHHQQSADSSRHSGIGHGQASSAVRDSGHRGYSGSQASDNEGHSEDSDTQSVSAHGQ
                     AGSHQQSHQESARGRSGETSGHSGSFLYQVSTHEQSESSHGWTGPSTRGRQGSRHEQA
                     QDSSRHSASQDGQDTIRGHPGSSRGGRQGYHHEHSVDSSGHSGSHHSHTTSQGRSDAS
                     RGQSGSRSASRTTRNEEQSGDGSRHSGSRHHEASTHADISRHSQAVQGQSEGSRRSRR
                     QGSSVSQDSDSEGHSEDSERWSGSASRNHHGSAQEQLRDGSRHPRSHQEDRAGHGHSA
                     DSSRQSGTRHTQTSSGGQAASSHEQARSSAGERHGSHHQQSADSSRHSGIGHGQASSA
                     VRDSGHRGYSGSQASDNEGHSEDSDTQSVSAHGQAGSHQQSHQESARGRSGETSGHSG
                     SFLYQVSTHEQSESSHGWTGPSTRGRQGSRHEQAQDSSRHSASQYGQDTIRGHPGSSR
                     GGRQGYHHEHSVDSSGHSGSHHSHTTSQGRSDASRGQSGSRSASRTTRNEEQSGDSSR
                     HSVSRHHEASTHADISRHSQAVQGQSEGSRRSRRQGSSVSQDSDSEGHSEDSERWSGS
                     ASRNHRGSVQEQSRHGSRHPRSHHEDRAGHGHSADRSRQSGTRHAETSSGGQAASSHE
                     QARSSPGERHGSRHQQSADSSRHSGIPRGQASSAVRDSRHWGSSGSQASDSEGHSEES
                     DTQSVSGHGQAGPHQQSHQESARDRSGGRSGRSGSFLYQVSTHEQSESAHGRTRTSTG
                     RRQGSHHEQARDSSRHSASQEGQDTIRGHPGSSRRGRQGSHYEQSVDRSGHSGSHHSH
                     TTSQGRSDASRGQSGSRSASRQTRNDEQSGDGSRHSWSHHHEASTQADSSRHSQSGQG
                     QSAGPRTSRNQGSSVSQDSDSQGHSEDSERWSGSASRNHRGSAQEQSRDGSRHPTSHH
                     EDRAGHGHSAESSRQSGTHHAENSSGGQAASSHEQARSSAGERHGSHHQQSADSSRHS
                     GIGHGQASSAVRDSGHRGSSGSQASDSEGHSEDSDTQSVSAHGQAGPHQQSHQESTRG
                     RSAGRSGRSGSFLYQVSTHEQSESAHGRAGPSTGGRQGSRHEQARDSSRHSASQEGQD
                     TIRGHPGSRRGGRQGSYHEQSVDRSGHSGSHHSHTTSQGRSDASHGQSGSRSASRETR
                     NEEQSGDGSRHSGSRHHEASTQADSSRHSQSGQGESAGSRRSRRQGSSVSQDSDSEAY
                     PEDSERRSESASRNHHGSSREQSRDGSRHPGSSHRDTASHVQSSPVQSDSSTAKEHGH
                     FSSLSQDSAYHSGIQSRGSPHSSSSYHYQSEGTERQKGQSGLVWRHGSYGSADYDYGE
                     SGFRHSQHGSVSYNSNPVVFKERSDICKASAFGKDHPRYYATYINKDPGLCGHSSDIS
                     KQLGFSQSQRYYYYE"
     exon            211..12793
                     /gene="FLG"
                     /gene_synonym="ATOD2; FLG-1; FLG1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      12773..12778
                     /regulatory_class="polyA_signal_sequence"
                     /gene="FLG"
                     /gene_synonym="ATOD2; FLG-1; FLG1"
                     /note="hexamer: AATAAA"
     polyA_site      12793
                     /gene="FLG"
                     /gene_synonym="ATOD2; FLG-1; FLG1"
                     /note="major polyA site"
ORIGIN      
        1 acccagcagg ctccttcagg ctacattcta tttgctcttt tggtgaacaa ggttcacatt
       61 tattgccaaa agatgtctac tctcctggaa aacatctttg ccataattaa tcttttcaag
      121 caatattcaa aaaaagataa aaacactgac acattgagta aaaaagagct gaaggaactt
      181 ctggaaaagg aatttcggca aatcctgaag aatccagatg acccagatat ggttgatgtc
      241 ttcatggatc acttggatat agaccacaac aagaaaattg acttcactga gtttcttctg
      301 atggtattca agttggctca agcatattat gagtctacca gaaaagagaa tttaccgata
      361 tcaggacaca agcacagaaa gcacagtcat catgataaac atgaagataa taaacaggaa
      421 gaaaacaaag aaaacagaaa aagaccctca agtctggaaa gaagaaacaa tagaaaaggg
      481 aataagggaa gatccaagag cccaagagaa acagggggga aaaggcatga atctagttct
      541 gaaaaaaaag aaagaaaagg atattcacct actcatagag aagaagaata tggaaaaaac
      601 catcataact caagtaaaaa agagaaaaac aagactgaaa atactagatt aggagacaat
      661 aggaagaggc taagtgaaag acttgaagag aaagaagaca atgaagaagg agtatatgat
      721 tatgaaaata caggaagaat gactcaaaaa tggatacaat caggccatat tgccacatat
      781 tacacaatcc aggatgaagc ctatgacacc actgatagtc tattagaaga aaacaaaata
      841 tatgaaagat caaggtcatc tgatggcaaa tcatcatctc aagtgaacag gtcaagacat
      901 gaaaatacaa gccaggtacc attgcaggag tccaggacaa gaaagcgtag gggatccaga
      961 gttagccagg acagggacag tgagggacac tcagaagact ctgagaggca ctctgggtcg
     1021 gcttccagaa accatcatgg atctgcgtgg gagcagtcaa gagatggctc cagacacccc
     1081 aggtcccatg atgaagacag agccagtcat gggcactctg cagacagctc cagacaatca
     1141 ggcactcgtc acgcagagac ttcctctcgt ggacagactg catcatccca tgaacaggca
     1201 agatcaagtc caggagaaag acatggatcc ggccaccagc agtcagcaga cagctccaga
     1261 cactcagcca ctgggcgcgg gcaagcttca tctgcagtca gcgatcgtgg acaccggggg
     1321 tctagcggta gtcaggccag tgacagtgag ggacattcag aaaactcaga cacacaatca
     1381 gtgtcaggcc acggaaaggc tgggctgaga cagcagagcc accaagagtc cacacgtggc
     1441 cggtcagggg aacggtctgg acgttcaggg tcttccctct accaggtgag cactcatgaa
     1501 cagcctgact ctgcccatgg acggaccggg accagcactg gaggaagaca aggatcgcac
     1561 cacgagcagg cacgagacag ctccaggcat tcagcgtccc aagagggtca ggacaccatt
     1621 cgtggacacc cggggtcaag cagaggagga aggcagggat cccaccacga gcaatcggta
     1681 aataggtctg gacactcagg ttcccatcac agccacacca catcccaggg aaggtctgat
     1741 gcctcccatg ggcagtcagg atccagaagt gcaagcagac aaacacgaaa tgaggaacaa
     1801 tcaggagacg gcaccaggca ctcagggtca cgtcatcatg aagcttcctc tcaggctgac
     1861 agctctagac actcacaggt gggccaggga caatcatcgg ggcccaggac aagtaggaac
     1921 cagggatcca gtgttagcca ggacagtgac agtcagggac actcagaaga ctctgagagg
     1981 tggtctgggt ctgcttccag aaaccatcat ggatctgctc aggagcagtc aagagatggc
     2041 tccagacacc ccaggtccca tcacgaagac agagctggtc atgggcactc tgcagacagc
     2101 tccagaaaat caggcactcg tcacacacag aattcctcta gtggacaggc tgcgtcatcc
     2161 catgaacagg caagatcaag tgcaggagaa agacatggat cccgccacca gctccagtca
     2221 gcagacagct ccagacactc aggcactggg cacggacaag cttcatctgc agtcagagac
     2281 agtggacacc gagggtccag tggtagtcag gccactgaca gtgagggaca ttcagaagac
     2341 tcagacacac agtcagtgtc aggccatgga caggctggtc accatcagca gagccaccaa
     2401 gagtccgcac gtgaccggtc aggggaaagg tctcgacgtt cagggtcttt cctctaccag
     2461 gtgagcactc ataaacagtc tgagtcctcc catggatgga cagggcccag cactggagta
     2521 agacaaggat cccaccatga gcaggcacga gacaactcca ggcactcagc atcccaagat
     2581 ggtcaggaca ccattcgtgg acacccgggg tcaagcagaa gaggaaggca ggggtcccac
     2641 cacgagcaat cggtagatag gtctggacac tcagggtccc atcacagcca caccacatcc
     2701 cagggaaggt ctgatgcctc ccgtgggcag tcaggatcca gaagtgcaag cagaacaaca
     2761 cgtaatgagg aacaatcaag agacggctcc aggcactcag ggtcacgtca ccatgaagct
     2821 tcctctcatg ccgacatctc tagacactca caggcaggcc agggacaatc agaggggtcc
     2881 aggacaagca ggcgccaggg atccagtgtt agccaggaca gtgacagtga gggacattca
     2941 gaagactctg agaggtggtc tgggtctgct tccagaaacc atcgtggatc tgctcaggag
     3001 cagtcaagac atggctccag acaccccagg tcccatcacg aagacagagc cggtcacggg
     3061 cactctgcag acagctccag acaatcagga actcctcacg cagagacttc ctctggtgga
     3121 caggctgcgt catcccatga acaggcaaga tcaagtccag gagaaagaca cggatcccgc
     3181 caccagcagt cagcagacag ctccagacac tcaggcattc cgcgcagaca agcttcatct
     3241 gcagtcagag acagtggaca ctgggggtcc agtggtagtc aggccagtga tagtgaggga
     3301 cattcagagg agtcagacac acagtcagtg tcaggccatg gacaggatgg gccccatcag
     3361 cagagccacc aagagtccgc acgtgactgg tcagggggaa ggtctggacg ttcagggtct
     3421 ttcatctacc aggtgagcac tcatgaacag tctgagtctg cccatgggcg gaccaggacc
     3481 agcactggac gaagacaagg atcccaccac gagcaggcac gagacagctc caggcactca
     3541 gcgtcccaag agggtcagga caccattcgt gcacacccgg ggtcaaggag aggaggaagg
     3601 cagggatccc accatgagca atcggtagat agatctggac actcagggtc ccatcacagc
     3661 cacaccacat cccagggaag gtctgatgcc tcccatgggc agtcaggatc cagaagtgca
     3721 agcagacaaa ctcgtaagga caaacaatca ggagacggct ccaggcactc agggtcacgt
     3781 caccatgaag ctgcctcttg ggctgacagc tctagacact cacaggtggg acaggaacaa
     3841 tcatcggggt ccaggacaag caggcaccag ggatccagtg ttagccagga cagtgacagt
     3901 gagagacact cagacgactc cgagaggttg tctgggtctg cttccagaaa ccatcatgga
     3961 tcttctcggg agcagtcaag agatggctcc agacaccctg ggttccatca agaagacaga
     4021 gccagtcacg ggcactctgc agacagctcc agacaatcag gcactcatca cacagagtct
     4081 tcctctcatg gacaggctgt gtcatcccat gaacaggcaa gatcaagtcc aggagaaaga
     4141 catggatccc gccaccagca gtcagcagac agctccagac actcaggcat tgggcacaga
     4201 caagcttcat ctgcagtcag agacagtgga caccgagggt ccagtggtag tcaggtcact
     4261 aacagtgagg gacattcaga agactcagac acacagtcag tgtcagccca cggacaagct
     4321 gggccccatc agcagagcca caaagagtcc gcacgtggcc agtcagggga aagctctgga
     4381 cgttcaaggt ctttcctcta ccaggtgagc tctcatgaac agtctgagtc cacacacgga
     4441 cagactgcac ccagcactgg aggaagacaa ggatcccgcc atgagcaggc acgaaacagc
     4501 tctaggcact cagcatccca agacggtcag gacaccattc gtggacaccc ggggtcaagc
     4561 agaggaggaa ggcagggatc ctaccacgag caatcagtag ataggtctgg acactcaggg
     4621 taccatcaca gccacaccac accccaggga aggtctgatg cctcccatgg gcagtcagga
     4681 cccagaagtg caagcaggca aacaagaaat gaggaacaat caggagacgg ctccaggcac
     4741 tcagggtcac gtcaccatga accttccact cgggccggca gctctagaca ctcacaggtg
     4801 ggccagggag aatcagcggg gtccaagaca agcaggcgcc agggatccag tgttagtcag
     4861 gacagggaca gtgagggaca ctcagaagac tctgagaggc ggtctgagtc ggcttccaga
     4921 aaccattatg gatctgctcg ggagcagtca agacatggct ccaggaaccc caggtcccat
     4981 caagaagata gagccagtca tgggcactct gcagagagct ccagacaatc aggcactcgt
     5041 catgcagaga cttcctctgg tggacaggct gcatcatccc aggaacaggc aaggtcaagt
     5101 ccaggagaaa gacatggatc ccgccaccag cagtcagcag acagctccac agactcaggc
     5161 actgggcgca gacaagattc atctgtagtc ggagacagtg gaaaccgagg gtccagtggt
     5221 agccaggcca gtgacagcga gggacactca gaagagtcag acacacagtc agtgtcagcc
     5281 cacggacagg ctgggcccca tcagcagagc caccaagagt ccacacgtgg ccagtcaggg
     5341 gaaaggtctg gacgttcagg gtctttcctc taccaggtga gcactcatga acagtctgag
     5401 tccgcccatg gacgcacagg gcccagcact ggaggaagac aaagatcccg ccacgagcag
     5461 gcacgagaca gctccaggca ctcagcgtcc caagagggtc aggacaccat tcgtggacac
     5521 ccagggtcaa gcagaggagg aaggcaggga tcccactatg agcaatcggt agatagttct
     5581 ggacactcag ggtctcatca cagccacacc acgtcccagg aaaggtctga tgtctcccgt
     5641 gggcagtcag gatccagaag tgtcagcaga caaacacgta atgagaaaca atcaggagac
     5701 ggctccaggc actcagggtc gcgtcaccat gaagcttcct ctcgggccga cagctctaga
     5761 cactcgcagg tgggccaggg acaatcatca gggcccagga caagcaggaa ccagggatcc
     5821 agtgttagcc aggacagtga cagtcaggga cactcagaag actctgagag gtggtctggg
     5881 tctgcttcca gaaaccatct tggatctgct tgggagcagt caagagatgg ctccagacac
     5941 cctgggtccc atcacgaaga cagagccggt cacgggcact ctgcagacag ctccagacaa
     6001 tcaggcactc gtcacacaga gtcttcctct cgtggacagg ctgcgtcatc ccatgaacag
     6061 gcaagatcaa gtgcaggaga aagacatgga tcccaccacc agctccagtc agcagacagc
     6121 tccagacact caggcattgg gcatggacaa gcttcatctg cagtcagaga cagtggacac
     6181 cgagggtaca gtggtagtca ggccagtgac agtgagggac attcagaaga ctcagacaca
     6241 cagtcagtgt cagcacaggg aaaagctggg ccccatcagc agagccacaa agagtccgca
     6301 cgtggccagt caggggaaag ctctggacgt tcagggtctt tcctctacca ggtgagcact
     6361 catgaacagt ctgagtccac ccatggacag tctgcgccca gcactggagg aagacaagga
     6421 tcccattatg atcaggcaca agacagctcc aggcactcag catcccaaga gggtcaggac
     6481 accattcgtg gacacccggg gccaagcaga ggaggaagac aggggtccca ccaagagcaa
     6541 tcggtagata ggtctggaca ctcagggtct catcacagcc acaccacatc ccagggaagg
     6601 tctgatgcct cccgtgggca gtcaggatcc agaagtgcaa gcagaaaaac atatgacaag
     6661 gaacaatcag gagatggctc taggcactca gggtcgcatc atcatgaagc ttcctcttgg
     6721 gccgacagct ctagacactc actggtgggc cagggacaat catcagggcc caggacaagc
     6781 aggccccggg gatccagtgt tagccaggac agtgacagtg agggacactc agaagattct
     6841 gagaggcggt ctgggtctgc gtccagaaac catcatggat ctgctcagga gcagtcaaga
     6901 gatggctcca gacaccccag gtcccatcac gaagacagag ccggtcatgg gcactctgca
     6961 gagagctcca gacaatcagg cactcatcat gcagagaatt cctctggtgg acaggctgca
     7021 tcatcccatg aacaggcaag atcaagtgca ggagagagac acggatccca ccaccagcag
     7081 tcagcagaca gctccagaca ctcaggcatt gggcacggac aagcttcatc tgcagtcaga
     7141 gacagtggac accgagggtc cagtggtagt caggccagtg acagtgaggg acattcagaa
     7201 gactcagaca cacagtcagt gtcagcccac ggacaggctg ggccccatca gcagagccac
     7261 caagagtcca cacgtggccg gtcagcagga aggtctggac gttcagggtc tttcctctac
     7321 caggtgagca ctcatgaaca gtctgagtcc gcccatggac ggaccgggac cagcactgga
     7381 ggaagacaag gatcccacca caagcaggca cgagacagct ccaggcactc aacgtcccaa
     7441 gagggtcagg acaccattca tggacacccg gggtcaagca gtggaggaag gcagggatcc
     7501 cactacgagc aattggtaga tagatctgga cactcagggt ctcatcacag ccacaccaca
     7561 tcccagggaa ggtctgatgc ctcccatggg cactcaggat ccagaagtgc aagcagacaa
     7621 actcgtaacg atgaacaatc aggagacggc tccaggcact cagggtcgcg tcaccatgaa
     7681 gcttcctctc gggccgacag ctctggacac tcgcaggtgg gccagggaca atcagagggg
     7741 cccaggacaa gcaggaactg gggatccagt tttagccagg acagtgacag tcagggacac
     7801 tcagaagact ctgagaggtg gtctgggtct gcttccagaa accatcatgg atctgctcag
     7861 gagcagctaa gagatggctc cagacacccc aggtcccatc aagaagacag agctggtcat
     7921 gggcactctg cagacagctc cagacaatca ggcactcgtc acacacagac ttcctctggt
     7981 ggacaggctg catcatccca tgaacaggca agatcaagtg caggagaaag acatggatcc
     8041 caccaccagc agtcagcaga cagctccaga cactcaggca ttgggcacgg acaagcttca
     8101 tctgcagtca gagacagtgg acaccgaggg tacagtggta gtcaggccag tgacaatgag
     8161 ggacattcag aagactcaga cacacagtca gtgtcagccc acggacaggc tgggtcccat
     8221 cagcagagcc accaagagtc cgcacgtggc cggtcagggg aaacgtctgg acattcagga
     8281 tctttcctct accaggtgag cactcatgaa cagtctgagt cctcccatgg atggacgggg
     8341 cccagcacta gaggaagaca aggatcccgc catgagcagg cacaagacag ctccaggcac
     8401 tcagcatccc aagacggtca ggacaccatt cgtggacacc cggggtcaag cagaggagga
     8461 aggcaggggt accaccacga gcattcggta gatagctctg gacactcagg gtcccatcac
     8521 agccacacca catcccaggg aaggtctgat gcctcccgtg ggcagtcagg atccagaagt
     8581 gcaagcagaa caacacgtaa tgaggaacaa tcaggagacg gctccaggca ctcagggtcg
     8641 cgtcaccatg aagcttccac tcatgccgac atctctagac actcacaggc agtccaggga
     8701 caatcagagg ggtccaggag aagcaggcgc cagggatcca gtgtgagcca ggacagtgac
     8761 agtgagggac attcagaaga ctctgagagg tggtctgggt ctgcttccag aaaccatcat
     8821 ggatctgctc aggagcagct aagagatggc tccagacacc ccaggtccca tcaagaagac
     8881 agagctggtc atgggcactc tgcagacagc tccagacaat caggcactcg tcacacacag
     8941 acttcctctg gtggacaggc tgcatcatcc catgaacagg caagatcaag tgcaggagaa
     9001 agacatggat cccaccacca gcagtcagca gacagctcca gacactcagg cattgggcac
     9061 ggacaagctt catctgcagt cagagacagt ggacaccgag ggtacagtgg tagtcaggcc
     9121 agtgacaatg agggacattc agaagactca gacacacagt cagtgtcagc ccacggacag
     9181 gctgggtccc atcagcagag ccaccaagag tccgcacgtg gccggtcagg ggaaacgtct
     9241 ggacattcag gatctttcct ctaccaggtg agcactcatg aacagtctga gtcctcccat
     9301 ggatggacgg ggcccagcac tagaggaaga caaggatccc gccatgagca ggcacaagac
     9361 agctccaggc actcagcatc ccaatacggt caggacacca ttcgtggaca cccggggtca
     9421 agcagaggag gaaggcaggg gtaccaccac gagcattcgg tagatagctc tggacactca
     9481 gggtcccatc acagccacac cacatcccag ggaaggtctg atgcctcccg tgggcagtca
     9541 ggatccagaa gtgcaagcag aacaacacgt aatgaggaac aatcaggaga cagctccagg
     9601 cactcagtgt cacgtcacca tgaagcttcc actcatgccg acatctctag acactcacag
     9661 gcagtccagg gacaatcaga ggggtccagg agaagcaggc gccagggatc cagtgtgagc
     9721 caggacagtg acagtgaggg acattcagaa gactctgaga ggtggtctgg gtctgcttcc
     9781 agaaaccatc gtggatctgt tcaggagcag tcaaggcacg gctccagaca ccccaggtcc
     9841 catcacgaag acagagccgg tcacgggcac tctgcagacc gctccagaca atcaggcact
     9901 cgtcacgcag agacttcctc tggtggacag gctgcatcat cccatgaaca ggcaagatca
     9961 agtccaggag agagacacgg atcccgccac cagcagtcag cagacagctc cagacactca
    10021 ggcattccgc gtggacaagc ttcatctgca gtcagagaca gtagacactg ggggtccagt
    10081 ggtagtcagg ccagtgatag tgagggacat tcagaagagt cagacacaca gtcagtgtca
    10141 ggccatggac aggctgggcc ccatcagcag agccaccaag agtccgcacg tgaccggtca
    10201 gggggaaggt ctggacgttc agggtctttc ctctaccagg tgagcactca tgaacagtct
    10261 gagtctgccc atgggcggac caggaccagc actggacgaa gacaaggatc ccaccacgag
    10321 caggcacgag acagctccag gcactcagcg tcccaagagg gtcaggacac cattcgtgga
    10381 cacccggggt caagcagaag aggaaggcag ggatcccact acgagcaatc ggtagatagg
    10441 tctggacact cagggtccca tcacagccac accacatccc agggaaggtc tgatgcctcc
    10501 cgtgggcagt caggatccag aagtgccagc agacaaactc gtaatgacga acaatcagga
    10561 gatggctcca ggcactcatg gtcgcatcac catgaagctt ccactcaggc ggacagctct
    10621 agacactcac agtccggcca gggacaatca gcggggccca ggacaagcag gaaccaggga
    10681 tccagtgtta gccaggacag tgacagtcag ggacactcag aagactctga gaggtggtct
    10741 gggtctgctt ccagaaacca tcgtggatct gctcaggagc agtcaagaga tggctccaga
    10801 caccccacgt cccatcacga agacagagcc ggtcacgggc actctgcaga gagctccaga
    10861 caatcaggca ctcatcatgc agagaattcc tctggtggac aggctgcatc atcccatgaa
    10921 caggcaagat caagtgcagg agagagacat ggatcccacc accagcagtc agcagacagc
    10981 tccagacact caggcattgg gcacggacaa gcttcatctg cagtcagaga cagtggacac
    11041 cgagggtcca gtggtagtca ggccagtgac agtgagggac attcagaaga ctcagacaca
    11101 cagtcagtgt cagcccacgg acaggctggg ccccatcagc agagccacca agagtccaca
    11161 cgtggccggt cagcaggaag gtctggacgt tcagggtctt tcctctacca ggtgagcact
    11221 catgaacagt ctgagtctgc ccatggacgg gctgggccca gtactggagg aagacaagga
    11281 tcccgccacg agcaggcacg agacagctcc aggcactcag cgtcccaaga gggtcaggac
    11341 accattcgtg gacacccggg gtcaaggaga ggaggaagac agggatccta ccacgagcaa
    11401 tcggtagata ggtctggaca ctcagggtcc catcacagcc acaccacatc ccagggaagg
    11461 tctgatgcct cccatgggca gtcaggatcc agaagtgcaa gcagagaaac acgtaatgag
    11521 gaacagtcag gagacggctc caggcactca gggtcgcgtc accatgaagc ttccactcag
    11581 gctgacagct ctagacactc acagtccggc cagggtgaat cagcggggtc caggagaagc
    11641 aggcgccagg gatccagtgt tagccaggac agtgacagtg aggcataccc agaggactct
    11701 gagaggcgat ctgagtctgc ttccagaaac catcatggat cttctcggga gcagtcaaga
    11761 gatggctcca gacaccccgg atcctctcac cgcgatacag ccagtcatgt acagtcttca
    11821 cctgtacagt cagactctag taccgctaag gaacatggtc actttagtag tctttcacaa
    11881 gattctgcgt atcactcagg aatacagtca cgtggcagtc ctcacagttc tagttcttat
    11941 cattatcaat ctgagggcac tgaaaggcaa aaaggtcaat caggtttagt ttggagacat
    12001 ggcagctatg gtagtgcaga ttatgattat ggtgaatccg ggtttagaca ctctcagcac
    12061 ggaagtgtta gttacaattc caatcctgtt gttttcaagg aaagatctga tatctgtaaa
    12121 gcaagtgcgt ttggtaaaga tcatccaagg tattatgcaa cgtatattaa taaggaccca
    12181 ggtttatgtg gccattctag tgatatatcg aaacaactgg gatttagtca gtcacagaga
    12241 tactattact atgagtaaga aattaatggc aaaggaatta atccaagaat agaagaatga
    12301 agcaagttca ctttcaatca agaaacttca taatactttc agggaagtta tcttttcctg
    12361 tcaatctgtt taaaatatgc tatagtattt cattagtttg gtggtagctt atttttattg
    12421 tgtaatgatc tttaaacgct atatttcaga aatattaaat ggaagaaatc aatatcatgg
    12481 agagctaact ttagaaaact agctggagta ttttaggaga ttctgggtca agtaatgttt
    12541 tatgtttttg aaagtttaag ttttagacac tccccaaatt tctaaattaa tctttttcag
    12601 aaatatcgaa ggagccaaaa atataaaaca gttctgtata ccaaagtggc tatatcaaca
    12661 tcagggctag cacatctttc tctattatcc ttctattgga attctagtat tctgtattca
    12721 aaaaatcatc ttggacataa ttaatattat agtaagctgc atctaaatta aaaataaact
    12781 attcatcata taa
//
