FILA_HUMAN
ID FILA_HUMAN Reviewed; 4061 AA.
AC P20930; Q01720; Q5T583; Q9UC71;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Filaggrin;
GN Name=FLG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-591, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=1429717; DOI=10.1016/s0021-9258(18)35905-2;
RA Presland R.B., Haydock P.V., Fleckman P., Nirunsuksiri W., Dale B.A.;
RT "Characterization of the human epidermal profilaggrin gene. Genomic
RT organization and identification of an S-100-like calcium binding domain at
RT the amino terminus.";
RL J. Biol. Chem. 267:23772-23781(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2389-2804.
RX PubMed=2740331; DOI=10.1073/pnas.86.13.4848;
RA McKinley-Grant L.J., Idler W.W., Bernstein I.A., Parry D.A.D.,
RA Cannizzaro L., Croce C.M., Huebner K., Lessin S.R., Steinert P.M.;
RT "Characterization of a cDNA clone encoding human filaggrin and localization
RT of the gene to chromosome region 1q21.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4848-4852(1989).
RN [4]
RP PROTEIN SEQUENCE OF 2741-2760 AND 3065-3084, AND N-TERMINAL PROCESSING.
RC TISSUE=Foreskin;
RX PubMed=7612609; DOI=10.1021/bi00027a018;
RA Thulin C.D., Walsh K.A.;
RT "Identification of the amino terminus of human filaggrin using differential
RT LC/MS techniques: implications for profilaggrin processing.";
RL Biochemistry 34:8687-8692(1995).
RN [5]
RP PROTEIN SEQUENCE OF 796-823; 2741-2760 AND 3065-3084, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Tear;
RX PubMed=25946035; DOI=10.1021/acs.jproteome.5b00179;
RA Azkargorta M., Soria J., Ojeda C., Guzman F., Acera A., Iloro I.,
RA Suarez T., Elortza F.;
RT "Human basal tear peptidome characterization by CID, HCD, and ETD followed
RT by in silico and in vitro analyses for antimicrobial peptide
RT identification.";
RL J. Proteome Res. 14:2649-2658(2015).
RN [6]
RP CITRULLINATION.
RX PubMed=8780679; DOI=10.1006/bbrc.1996.1240;
RA Senshu T., Kan S., Ogawa H., Manabe M., Asaga H.;
RT "Preferential deimination of keratin K1 and filaggrin during the terminal
RT differentiation of human epidermis.";
RL Biochem. Biophys. Res. Commun. 225:712-719(1996).
RN [7]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ATOD2.
RX PubMed=16815158; DOI=10.1016/j.jaci.2006.05.004;
RA Weidinger S., Illig T., Baurecht H., Irvine A.D., Rodriguez E.,
RA Diaz-Lacava A., Klopp N., Wagenpfeil S., Zhao Y., Liao H., Lee S.P.,
RA Palmer C.N.A., Jenneck C., Maintz L., Hagemann T., Behrendt H., Ring J.,
RA Nothen M.M., McLean W.H.I., Novak N.;
RT "Loss-of-function variations within the filaggrin gene predispose for
RT atopic dermatitis with allergic sensitizations.";
RL J. Allergy Clin. Immunol. 118:214-219(2006).
RN [8]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ATOD2.
RX PubMed=17030239; DOI=10.1016/j.jaci.2006.07.026;
RA Marenholz I., Nickel R., Rueschendorf F., Schulz F., Esparza-Gordillo J.,
RA Kerscher T., Grueber C., Lau S., Worm M., Keil T., Kurek M., Zaluga E.,
RA Wahn U., Lee Y.-A.;
RT "Filaggrin loss-of-function mutations predispose to phenotypes involved in
RT the atopic march.";
RL J. Allergy Clin. Immunol. 118:866-871(2006).
RN [9]
RP INVOLVEMENT IN ICHTHYOSIS VULGARIS.
RX PubMed=16444271; DOI=10.1038/ng1743;
RA Smith F.J.D., Irvine A.D., Terron-Kwiatkowski A., Sandilands A.,
RA Campbell L.E., Zhao Y., Liao H., Evans A.T., Goudie D.R., Lewis-Jones S.,
RA Arseculeratne G., Munro C.S., Sergeant A., O'Regan G., Bale S.J.,
RA Compton J.G., DiGiovanna J.J., Presland R.B., Fleckman P., McLean W.H.I.;
RT "Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis
RT vulgaris.";
RL Nat. Genet. 38:337-342(2006).
RN [10]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ATOD2.
RX PubMed=16550169; DOI=10.1038/ng1767;
RA Palmer C.N.A., Irvine A.D., Terron-Kwiatkowski A., Zhao Y., Liao H.,
RA Lee S.P., Goudie D.R., Sandilands A., Campbell L.E., Smith F.J.D.,
RA O'Regan G.M., Watson R.M., Cecil J.E., Bale S.J., Compton J.G.,
RA DiGiovanna J.J., Fleckman P., Lewis-Jones S., Arseculeratne G.,
RA Sergeant A., Munro C.S., El Houate B., McElreavey K., Halkjaer L.B.,
RA Bisgaard H., Mukhopadhyay S., McLean W.H.I.;
RT "Common loss-of-function variants of the epidermal barrier protein
RT filaggrin are a major predisposing factor for atopic dermatitis.";
RL Nat. Genet. 38:441-446(2006).
RN [11]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ATOD2.
RX PubMed=17291859; DOI=10.1016/j.jaci.2006.12.646;
RA Nomura T., Sandilands A., Akiyama M., Liao H., Evans A.T., Sakai K.,
RA Ota M., Sugiura H., Yamamoto K., Sato H., Palmer C.N.A., Smith F.J.D.,
RA McLean W.H.I., Shimizu H.;
RT "Unique mutations in the filaggrin gene in Japanese patients with
RT ichthyosis vulgaris and atopic dermatitis.";
RL J. Allergy Clin. Immunol. 119:434-440(2007).
RN [12]
RP TISSUE SPECIFICITY, AND INDUCTION BY CALCIUM.
RX PubMed=19384417; DOI=10.1371/journal.pone.0005227;
RA Wu Z., Hansmann B., Meyer-Hoffert U., Glaser R., Schroder J.M.;
RT "Molecular identification and expression analysis of filaggrin-2, a member
RT of the S100 fused-type protein family.";
RL PLoS ONE 4:E5227-E5227(2009).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=21531719; DOI=10.1074/jbc.m110.197400;
RA Hsu C.Y., Henry J., Raymond A.A., Mechin M.C., Pendaries V., Nassar D.,
RA Hansmann B., Balica S., Burlet-Schiltz O., Schmitt A.M., Takahara H.,
RA Paul C., Serre G., Simon M.;
RT "Deimination of human filaggrin-2 promotes its proteolysis by calpain 1.";
RL J. Biol. Chem. 286:23222-23233(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Aggregates keratin intermediate filaments and promotes
CC disulfide-bond formation among the intermediate filaments during
CC terminal differentiation of mammalian epidermis.
CC -!- INTERACTION:
CC P20930; Q9Y337: KLK5; NbExp=4; IntAct=EBI-1058782, EBI-9057524;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic granule
CC {ECO:0000269|PubMed:16710414}. Note=In the stratum granulosum of the
CC epidermis, localized within keratohyalin granules (PubMed:1429717). In
CC granular keratinocytes and in lower corneocytes, colocalizes with
CC calpain-1/CAPN1 (PubMed:21531719). {ECO:0000269|PubMed:1429717,
CC ECO:0000269|PubMed:21531719}.
CC -!- TISSUE SPECIFICITY: Expressed in skin, thymus, stomach, tonsils,
CC testis, placenta, kidney, pancreas, mammary gland, bladder, thyroid,
CC salivary gland and trachea, but not detected in heart, brain, liver,
CC lung, bone marrow, small intestine, spleen, prostate, colon, or adrenal
CC gland (PubMed:19384417). In the skin, mainly expressed in stratum
CC granulosum of the epidermis (PubMed:1429717) (PubMed:19384417).
CC {ECO:0000269|PubMed:1429717, ECO:0000269|PubMed:19384417}.
CC -!- INDUCTION: In cultured foreskin fibroblasts, up-regulated in response
CC to Ca(2+) stimulation. {ECO:0000269|PubMed:19384417}.
CC -!- PTM: Filaggrin is initially synthesized as a large, insoluble, highly
CC phosphorylated precursor containing many tandem copies of 324 AA, which
CC are not separated by large linker sequences. During terminal
CC differentiation it is dephosphorylated and proteolytically cleaved. The
CC N-terminal of the mature protein is heterogeneous, and is blocked by
CC the formation of pyroglutamate.
CC -!- PTM: Undergoes deimination of some arginine residues (citrullination).
CC {ECO:0000269|PubMed:8780679}.
CC -!- DISEASE: Ichthyosis vulgaris (VI) [MIM:146700]: The most common form of
CC ichthyosis inherited as an autosomal dominant trait. It is
CC characterized by palmar hyperlinearity, keratosis pilaris and a fine
CC scale that is most prominent over the lower abdomen, arms, and legs.
CC Ichthyosis vulgaris is characterized histologically by absent or
CC reduced keratohyalin granules in the epidermis and mild hyperkeratosis.
CC The disease can be associated with frequent asthma, eczema or hay
CC fever. {ECO:0000269|PubMed:16444271}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Dermatitis atopic 2 (ATOD2) [MIM:605803]: Atopic dermatitis is
CC a complex, inflammatory disease with multiple alleles at several loci
CC thought to be involved in the pathogenesis. It commonly begins in
CC infancy or early childhood and is characterized by a chronic relapsing
CC form of skin inflammation, a disturbance of epidermal barrier function
CC that culminates in dry skin, and IgE-mediated sensitization to food and
CC environmental allergens. It is manifested by lichenification,
CC excoriation, and crusting, mainly on the flexural surfaces of the elbow
CC and knee. {ECO:0000269|PubMed:16550169, ECO:0000269|PubMed:16815158,
CC ECO:0000269|PubMed:17030239, ECO:0000269|PubMed:17291859}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the S100-fused protein family. {ECO:0000305}.
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DR EMBL; AL356504; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L01089; AAA60177.1; -; Genomic_DNA.
DR EMBL; M24355; AAA52454.1; -; mRNA.
DR CCDS; CCDS30860.1; -.
DR PIR; A32947; A32947.
DR PIR; A45135; A45135.
DR PIR; A48118; A48118.
DR RefSeq; NP_002007.1; NM_002016.1.
DR PDB; 4PCW; X-ray; 2.20 A; A/B/C/D=1-92.
DR PDBsum; 4PCW; -.
DR SMR; P20930; -.
DR BioGRID; 108601; 135.
DR IntAct; P20930; 25.
DR STRING; 9606.ENSP00000357789; -.
DR GlyGen; P20930; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P20930; -.
DR PhosphoSitePlus; P20930; -.
DR BioMuta; FLG; -.
DR DMDM; 84028206; -.
DR MassIVE; P20930; -.
DR PaxDb; P20930; -.
DR PeptideAtlas; P20930; -.
DR PRIDE; P20930; -.
DR ProteomicsDB; 53826; -.
DR TopDownProteomics; P20930; -.
DR Antibodypedia; 3694; 566 antibodies from 33 providers.
DR DNASU; 2312; -.
DR Ensembl; ENST00000368799.2; ENSP00000357789.1; ENSG00000143631.11.
DR GeneID; 2312; -.
DR KEGG; hsa:2312; -.
DR MANE-Select; ENST00000368799.2; ENSP00000357789.1; NM_002016.2; NP_002007.1.
DR UCSC; uc001ezu.1; human.
DR CTD; 2312; -.
DR DisGeNET; 2312; -.
DR GeneCards; FLG; -.
DR HGNC; HGNC:3748; FLG.
DR HPA; ENSG00000143631; Tissue enriched (skin).
DR MalaCards; FLG; -.
DR MIM; 135940; gene.
DR MIM; 146700; phenotype.
DR MIM; 605803; phenotype.
DR neXtProt; NX_P20930; -.
DR OpenTargets; ENSG00000143631; -.
DR Orphanet; 462; NON RARE IN EUROPE: Autosomal dominant ichthyosis vulgaris.
DR PharmGKB; PA28169; -.
DR VEuPathDB; HostDB:ENSG00000143631; -.
DR eggNOG; KOG3544; Eukaryota.
DR GeneTree; ENSGT00940000154467; -.
DR HOGENOM; CLU_224021_0_0_1; -.
DR InParanoid; P20930; -.
DR OMA; QDTIRGH; -.
DR OrthoDB; 30610at2759; -.
DR PhylomeDB; P20930; -.
DR TreeFam; TF338665; -.
DR PathwayCommons; P20930; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; P20930; -.
DR SIGNOR; P20930; -.
DR BioGRID-ORCS; 2312; 7 hits in 1068 CRISPR screens.
DR ChiTaRS; FLG; human.
DR GeneWiki; Filaggrin; -.
DR GenomeRNAi; 2312; -.
DR Pharos; P20930; Tbio.
DR PRO; PR:P20930; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P20930; protein.
DR Bgee; ENSG00000143631; Expressed in upper leg skin and 104 other tissues.
DR Genevisible; P20930; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0001533; C:cornified envelope; IDA:CAFA.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0036457; C:keratohyalin granule; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0030280; F:structural constituent of skin epidermis; IDA:CAFA.
DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR GO; GO:0061436; P:establishment of skin barrier; IEP:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; TAS:BHF-UCL.
DR GO; GO:0018149; P:peptide cross-linking; IDA:CAFA.
DR CDD; cd00213; S-100; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR003303; Filaggrin.
DR InterPro; IPR034325; S-100_dom.
DR InterPro; IPR001751; S100/CaBP7/8-like_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR Pfam; PF03516; Filaggrin; 23.
DR Pfam; PF01023; S_100; 1.
DR PRINTS; PR00487; FILAGGRIN.
DR SMART; SM01394; S_100; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS00303; S100_CABP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Citrullination; Coiled coil; Developmental protein;
KW Direct protein sequencing; Ichthyosis; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..4061
FT /note="Filaggrin"
FT /id="PRO_0000144036"
FT DOMAIN 6..43
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 49..84
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REPEAT 258..306
FT /note="Filaggrin 1"
FT REPEAT 374..428
FT /note="Filaggrin 2"
FT REPEAT 579..630
FT /note="Filaggrin 3"
FT REPEAT 698..753
FT /note="Filaggrin 4"
FT REPEAT 904..955
FT /note="Filaggrin 5"
FT REPEAT 1023..1077
FT /note="Filaggrin 6"
FT REPEAT 1228..1279
FT /note="Filaggrin 7"
FT REPEAT 1347..1401
FT /note="Filaggrin 8"
FT REPEAT 1552..1603
FT /note="Filaggrin 9"
FT REPEAT 1671..1725
FT /note="Filaggrin 10"
FT REPEAT 1876..1927
FT /note="Filaggrin 11"
FT REPEAT 1995..2050
FT /note="Filaggrin 12"
FT REPEAT 2201..2252
FT /note="Filaggrin 13"
FT REPEAT 2320..2374
FT /note="Filaggrin 14"
FT REPEAT 2525..2576
FT /note="Filaggrin 15"
FT REPEAT 2644..2698
FT /note="Filaggrin 16"
FT REPEAT 2849..2900
FT /note="Filaggrin 17"
FT REPEAT 2968..3022
FT /note="Filaggrin 18"
FT REPEAT 3173..3224
FT /note="Filaggrin 19"
FT REPEAT 3292..3346
FT /note="Filaggrin 20"
FT REPEAT 3497..3548
FT /note="Filaggrin 21"
FT REPEAT 3616..3670
FT /note="Filaggrin 22"
FT REPEAT 3821..3872
FT /note="Filaggrin 23"
FT REGION 92..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 255..3971
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 186..216
FT /evidence="ECO:0000255"
FT COMPBIAS 109..212
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 263..285
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 286..355
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 356..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 460..494
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 527..574
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 575..595
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 596..627
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 648..679
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 680..700
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 701..715
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 716..750
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 759..773
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 774..788
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 789..819
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 843..869
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 870..895
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 896..921
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 922..950
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 951..965
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 973..998
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 999..1025
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1026..1040
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1059..1074
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1083..1127
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1128..1157
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1166..1193
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1194..1216
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1217..1244
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1245..1270
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1271..1289
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1296..1328
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1329..1349
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1350..1364
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1383..1470
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1518..1547
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1548..1568
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1569..1591
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1592..1652
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1653..1676
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1688..1722
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1731..1790
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1791..1805
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1824..1843
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1851..1871
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1872..1893
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1894..1924
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1953..1976
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1977..1997
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1998..2012
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2033..2047
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2054..2138
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2167..2189
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2190..2217
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2218..2247
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2248..2301
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2302..2322
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2323..2337
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2356..2371
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2380..2440
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2455..2476
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2491..2520
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2521..2541
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2542..2573
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2594..2619
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2620..2646
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2647..2661
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2681..2695
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2704..2764
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2796..2811
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2812..2844
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2845..2866
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2867..2895
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2896..2910
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2918..2943
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2944..2970
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2971..2985
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3005..3019
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3028..3088
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3120..3135
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3136..3168
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3169..3190
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3191..3219
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3220..3234
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3242..3276
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3277..3294
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3295..3309
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3328..3343
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3352..3367
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3382..3396
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3397..3426
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3448..3462
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3463..3492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3493..3513
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3514..3545
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3566..3597
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3598..3618
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3619..3633
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3652..3667
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3676..3726
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3787..3809
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3810..3837
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3838..3869
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3871..3907
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3908..3967
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 62
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 66
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 68
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 73
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT VARIANT 332
FT /note="G -> V (in dbSNP:rs41267154)"
FT /id="VAR_061049"
FT VARIANT 444
FT /note="G -> R (in dbSNP:rs11588170)"
FT /id="VAR_061050"
FT VARIANT 454
FT /note="T -> A (in dbSNP:rs2011331)"
FT /id="VAR_059155"
FT VARIANT 478
FT /note="P -> S (in dbSNP:rs11584340)"
FT /id="VAR_059156"
FT VARIANT 725
FT /note="T -> I (in dbSNP:rs3120655)"
FT /id="VAR_059157"
FT VARIANT 742
FT /note="S -> Y (in dbSNP:rs3120654)"
FT /id="VAR_061051"
FT VARIANT 1184
FT /note="S -> L (in dbSNP:rs3120649)"
FT /id="VAR_045968"
FT VARIANT 1376
FT /note="R -> G (in dbSNP:rs11581433)"
FT /id="VAR_045969"
FT VARIANT 1437
FT /note="R -> C (in dbSNP:rs12750571)"
FT /id="VAR_045970"
FT VARIANT 1482
FT /note="S -> Y (in dbSNP:rs11204978)"
FT /id="VAR_059158"
FT VARIANT 1684
FT /note="R -> H (in dbSNP:rs12407807)"
FT /id="VAR_061052"
FT VARIANT 1699
FT /note="R -> C (in dbSNP:rs12405278)"
FT /id="VAR_059159"
FT VARIANT 1750
FT /note="S -> F (in dbSNP:rs3120647)"
FT /id="VAR_059160"
FT VARIANT 1805
FT /note="A -> V (in dbSNP:rs12405241)"
FT /id="VAR_045971"
FT VARIANT 1816
FT /note="H -> Q (in dbSNP:rs12073613)"
FT /id="VAR_059161"
FT VARIANT 1891
FT /note="R -> Q (in dbSNP:rs12407748)"
FT /id="VAR_059162"
FT VARIANT 1961
FT /note="H -> Q (in dbSNP:rs3126079)"
FT /id="VAR_045972"
FT VARIANT 2022
FT /note="I -> T (in dbSNP:rs142592778)"
FT /id="VAR_045973"
FT VARIANT 2108
FT /note="A -> V (in dbSNP:rs7522925)"
FT /id="VAR_059163"
FT VARIANT 2119
FT /note="Y -> H (in dbSNP:rs7512553)"
FT /id="VAR_059164"
FT VARIANT 2194
FT /note="Y -> H (in dbSNP:rs2184953)"
FT /id="VAR_059165"
FT VARIANT 2507
FT /note="H -> Q (in dbSNP:rs3126074)"
FT /id="VAR_045974"
FT VARIANT 2540
FT /note="R -> Q (in dbSNP:rs148050570)"
FT /id="VAR_048472"
FT VARIANT 2545
FT /note="G -> R (in dbSNP:rs3126072)"
FT /id="VAR_059166"
FT VARIANT 2781
FT /note="D -> Y (in dbSNP:rs759244716)"
FT /id="VAR_048473"
FT VARIANT 3105
FT /note="Y -> D (in dbSNP:rs2065958)"
FT /id="VAR_059167"
FT VARIANT 3179
FT /note="V -> G (in dbSNP:rs2065957)"
FT /id="VAR_059168"
FT VARIANT 3371
FT /note="S -> F (in dbSNP:rs3120647)"
FT /id="VAR_048474"
FT VARIANT 3396
FT /note="S -> P (in dbSNP:rs528344105)"
FT /id="VAR_048475"
FT VARIANT 3415
FT /note="H -> Y (in dbSNP:rs7512553)"
FT /id="VAR_048476"
FT VARIANT 3427
FT /note="S -> Y (in dbSNP:rs11204978)"
FT /id="VAR_048477"
FT VARIANT 3436
FT /note="G -> A (in dbSNP:rs2065955)"
FT /id="VAR_033931"
FT VARIANT 3437
FT /note="H -> Q (in dbSNP:rs12073613)"
FT /id="VAR_048478"
FT VARIANT 3490
FT /note="R -> C (in dbSNP:rs113933537)"
FT /id="VAR_048479"
FT VARIANT 3503
FT /note="W -> G (in dbSNP:rs12728908)"
FT /id="VAR_059169"
FT VARIANT 3512
FT /note="Q -> R (in dbSNP:rs571269174)"
FT /id="VAR_048480"
FT VARIANT 3564
FT /note="R -> H (in dbSNP:rs7518080)"
FT /id="VAR_059170"
FT VARIANT 3584
FT /note="D -> N (in dbSNP:rs3814300)"
FT /id="VAR_048481"
FT VARIANT 3593
FT /note="E -> D (in dbSNP:rs12083389)"
FT /id="VAR_059171"
FT VARIANT 3630
FT /note="H -> Y (in dbSNP:rs9436065)"
FT /id="VAR_059172"
FT VARIANT 3695
FT /note="S -> F (in dbSNP:rs3120647)"
FT /id="VAR_048482"
FT VARIANT 3696
FT /note="T -> A (in dbSNP:rs537909579)"
FT /id="VAR_048483"
FT VARIANT 3720
FT /note="S -> P (in dbSNP:rs11584340)"
FT /id="VAR_048484"
FT VARIANT 3739
FT /note="H -> Y (in dbSNP:rs7512553)"
FT /id="VAR_048485"
FT VARIANT 3751
FT /note="S -> Y (in dbSNP:rs776603551)"
FT /id="VAR_048486"
FT VARIANT 3760
FT /note="G -> A (in dbSNP:rs768192328)"
FT /id="VAR_048487"
FT VARIANT 3761
FT /note="H -> Q (in dbSNP:rs755367746)"
FT /id="VAR_048488"
FT VARIANT 3814
FT /note="R -> C (in dbSNP:rs146212122)"
FT /id="VAR_048489"
FT VARIANT 3827
FT /note="G -> W (in dbSNP:rs140464988)"
FT /id="VAR_048490"
FT VARIANT 3908
FT /note="D -> N (in dbSNP:rs3814300)"
FT /id="VAR_048491"
FT VARIANT 3935
FT /note="S -> P (in dbSNP:rs3126065)"
FT /id="VAR_048492"
FT VARIANT 3970
FT /note="S -> L (in dbSNP:rs3814299)"
FT /id="VAR_048493"
FT CONFLICT 2444
FT /note="K -> Q (in Ref. 3; AAA52454)"
FT /evidence="ECO:0000305"
FT CONFLICT 2466
FT /note="P -> R (in Ref. 3; AAA52454)"
FT /evidence="ECO:0000305"
FT CONFLICT 2652
FT /note="E -> D (in Ref. 3; AAA52454)"
FT /evidence="ECO:0000305"
FT CONFLICT 2804
FT /note="H -> Q (in Ref. 3; AAA52454)"
FT /evidence="ECO:0000305"
FT HELIX 4..19
FT /evidence="ECO:0007829|PDB:4PCW"
FT HELIX 30..39
FT /evidence="ECO:0007829|PDB:4PCW"
FT TURN 43..46
FT /evidence="ECO:0007829|PDB:4PCW"
FT TURN 50..53
FT /evidence="ECO:0007829|PDB:4PCW"
FT HELIX 54..61
FT /evidence="ECO:0007829|PDB:4PCW"
FT HELIX 71..85
FT /evidence="ECO:0007829|PDB:4PCW"
SQ SEQUENCE 4061 AA; 435170 MW; 3F4B1181F04AD9C0 CRC64;
MSTLLENIFA IINLFKQYSK KDKNTDTLSK KELKELLEKE FRQILKNPDD PDMVDVFMDH
LDIDHNKKID FTEFLLMVFK LAQAYYESTR KENLPISGHK HRKHSHHDKH EDNKQEENKE
NRKRPSSLER RNNRKGNKGR SKSPRETGGK RHESSSEKKE RKGYSPTHRE EEYGKNHHNS
SKKEKNKTEN TRLGDNRKRL SERLEEKEDN EEGVYDYENT GRMTQKWIQS GHIATYYTIQ
DEAYDTTDSL LEENKIYERS RSSDGKSSSQ VNRSRHENTS QVPLQESRTR KRRGSRVSQD
RDSEGHSEDS ERHSGSASRN HHGSAWEQSR DGSRHPRSHD EDRASHGHSA DSSRQSGTRH
AETSSRGQTA SSHEQARSSP GERHGSGHQQ SADSSRHSAT GRGQASSAVS DRGHRGSSGS
QASDSEGHSE NSDTQSVSGH GKAGLRQQSH QESTRGRSGE RSGRSGSSLY QVSTHEQPDS
AHGRTGTSTG GRQGSHHEQA RDSSRHSASQ EGQDTIRGHP GSSRGGRQGS HHEQSVNRSG
HSGSHHSHTT SQGRSDASHG QSGSRSASRQ TRNEEQSGDG TRHSGSRHHE ASSQADSSRH
SQVGQGQSSG PRTSRNQGSS VSQDSDSQGH SEDSERWSGS ASRNHHGSAQ EQSRDGSRHP
RSHHEDRAGH GHSADSSRKS GTRHTQNSSS GQAASSHEQA RSSAGERHGS RHQLQSADSS
RHSGTGHGQA SSAVRDSGHR GSSGSQATDS EGHSEDSDTQ SVSGHGQAGH HQQSHQESAR
DRSGERSRRS GSFLYQVSTH KQSESSHGWT GPSTGVRQGS HHEQARDNSR HSASQDGQDT
IRGHPGSSRR GRQGSHHEQS VDRSGHSGSH HSHTTSQGRS DASRGQSGSR SASRTTRNEE
QSRDGSRHSG SRHHEASSHA DISRHSQAGQ GQSEGSRTSR RQGSSVSQDS DSEGHSEDSE
RWSGSASRNH RGSAQEQSRH GSRHPRSHHE DRAGHGHSAD SSRQSGTPHA ETSSGGQAAS
SHEQARSSPG ERHGSRHQQS ADSSRHSGIP RRQASSAVRD SGHWGSSGSQ ASDSEGHSEE
SDTQSVSGHG QDGPHQQSHQ ESARDWSGGR SGRSGSFIYQ VSTHEQSESA HGRTRTSTGR
RQGSHHEQAR DSSRHSASQE GQDTIRAHPG SRRGGRQGSH HEQSVDRSGH SGSHHSHTTS
QGRSDASHGQ SGSRSASRQT RKDKQSGDGS RHSGSRHHEA ASWADSSRHS QVGQEQSSGS
RTSRHQGSSV SQDSDSERHS DDSERLSGSA SRNHHGSSRE QSRDGSRHPG FHQEDRASHG
HSADSSRQSG THHTESSSHG QAVSSHEQAR SSPGERHGSR HQQSADSSRH SGIGHRQASS
AVRDSGHRGS SGSQVTNSEG HSEDSDTQSV SAHGQAGPHQ QSHKESARGQ SGESSGRSRS
FLYQVSSHEQ SESTHGQTAP STGGRQGSRH EQARNSSRHS ASQDGQDTIR GHPGSSRGGR
QGSYHEQSVD RSGHSGYHHS HTTPQGRSDA SHGQSGPRSA SRQTRNEEQS GDGSRHSGSR
HHEPSTRAGS SRHSQVGQGE SAGSKTSRRQ GSSVSQDRDS EGHSEDSERR SESASRNHYG
SAREQSRHGS RNPRSHQEDR ASHGHSAESS RQSGTRHAET SSGGQAASSQ EQARSSPGER
HGSRHQQSAD SSTDSGTGRR QDSSVVGDSG NRGSSGSQAS DSEGHSEESD TQSVSAHGQA
GPHQQSHQES TRGQSGERSG RSGSFLYQVS THEQSESAHG RTGPSTGGRQ RSRHEQARDS
SRHSASQEGQ DTIRGHPGSS RGGRQGSHYE QSVDSSGHSG SHHSHTTSQE RSDVSRGQSG
SRSVSRQTRN EKQSGDGSRH SGSRHHEASS RADSSRHSQV GQGQSSGPRT SRNQGSSVSQ
DSDSQGHSED SERWSGSASR NHLGSAWEQS RDGSRHPGSH HEDRAGHGHS ADSSRQSGTR
HTESSSRGQA ASSHEQARSS AGERHGSHHQ LQSADSSRHS GIGHGQASSA VRDSGHRGYS
GSQASDSEGH SEDSDTQSVS AQGKAGPHQQ SHKESARGQS GESSGRSGSF LYQVSTHEQS
ESTHGQSAPS TGGRQGSHYD QAQDSSRHSA SQEGQDTIRG HPGPSRGGRQ GSHQEQSVDR
SGHSGSHHSH TTSQGRSDAS RGQSGSRSAS RKTYDKEQSG DGSRHSGSHH HEASSWADSS
RHSLVGQGQS SGPRTSRPRG SSVSQDSDSE GHSEDSERRS GSASRNHHGS AQEQSRDGSR
HPRSHHEDRA GHGHSAESSR QSGTHHAENS SGGQAASSHE QARSSAGERH GSHHQQSADS
SRHSGIGHGQ ASSAVRDSGH RGSSGSQASD SEGHSEDSDT QSVSAHGQAG PHQQSHQEST
RGRSAGRSGR SGSFLYQVST HEQSESAHGR TGTSTGGRQG SHHKQARDSS RHSTSQEGQD
TIHGHPGSSS GGRQGSHYEQ LVDRSGHSGS HHSHTTSQGR SDASHGHSGS RSASRQTRND
EQSGDGSRHS GSRHHEASSR ADSSGHSQVG QGQSEGPRTS RNWGSSFSQD SDSQGHSEDS
ERWSGSASRN HHGSAQEQLR DGSRHPRSHQ EDRAGHGHSA DSSRQSGTRH TQTSSGGQAA
SSHEQARSSA GERHGSHHQQ SADSSRHSGI GHGQASSAVR DSGHRGYSGS QASDNEGHSE
DSDTQSVSAH GQAGSHQQSH QESARGRSGE TSGHSGSFLY QVSTHEQSES SHGWTGPSTR
GRQGSRHEQA QDSSRHSASQ DGQDTIRGHP GSSRGGRQGY HHEHSVDSSG HSGSHHSHTT
SQGRSDASRG QSGSRSASRT TRNEEQSGDG SRHSGSRHHE ASTHADISRH SQAVQGQSEG
SRRSRRQGSS VSQDSDSEGH SEDSERWSGS ASRNHHGSAQ EQLRDGSRHP RSHQEDRAGH
GHSADSSRQS GTRHTQTSSG GQAASSHEQA RSSAGERHGS HHQQSADSSR HSGIGHGQAS
SAVRDSGHRG YSGSQASDNE GHSEDSDTQS VSAHGQAGSH QQSHQESARG RSGETSGHSG
SFLYQVSTHE QSESSHGWTG PSTRGRQGSR HEQAQDSSRH SASQYGQDTI RGHPGSSRGG
RQGYHHEHSV DSSGHSGSHH SHTTSQGRSD ASRGQSGSRS ASRTTRNEEQ SGDSSRHSVS
RHHEASTHAD ISRHSQAVQG QSEGSRRSRR QGSSVSQDSD SEGHSEDSER WSGSASRNHR
GSVQEQSRHG SRHPRSHHED RAGHGHSADR SRQSGTRHAE TSSGGQAASS HEQARSSPGE
RHGSRHQQSA DSSRHSGIPR GQASSAVRDS RHWGSSGSQA SDSEGHSEES DTQSVSGHGQ
AGPHQQSHQE SARDRSGGRS GRSGSFLYQV STHEQSESAH GRTRTSTGRR QGSHHEQARD
SSRHSASQEG QDTIRGHPGS SRRGRQGSHY EQSVDRSGHS GSHHSHTTSQ GRSDASRGQS
GSRSASRQTR NDEQSGDGSR HSWSHHHEAS TQADSSRHSQ SGQGQSAGPR TSRNQGSSVS
QDSDSQGHSE DSERWSGSAS RNHRGSAQEQ SRDGSRHPTS HHEDRAGHGH SAESSRQSGT
HHAENSSGGQ AASSHEQARS SAGERHGSHH QQSADSSRHS GIGHGQASSA VRDSGHRGSS
GSQASDSEGH SEDSDTQSVS AHGQAGPHQQ SHQESTRGRS AGRSGRSGSF LYQVSTHEQS
ESAHGRAGPS TGGRQGSRHE QARDSSRHSA SQEGQDTIRG HPGSRRGGRQ GSYHEQSVDR
SGHSGSHHSH TTSQGRSDAS HGQSGSRSAS RETRNEEQSG DGSRHSGSRH HEASTQADSS
RHSQSGQGES AGSRRSRRQG SSVSQDSDSE AYPEDSERRS ESASRNHHGS SREQSRDGSR
HPGSSHRDTA SHVQSSPVQS DSSTAKEHGH FSSLSQDSAY HSGIQSRGSP HSSSSYHYQS
EGTERQKGQS GLVWRHGSYG SADYDYGESG FRHSQHGSVS YNSNPVVFKE RSDICKASAF
GKDHPRYYAT YINKDPGLCG HSSDISKQLG FSQSQRYYYY E
