ID WRN_MOUSE Reviewed; 1401 AA. AC O09053; O09050; Q80YP9; Q9JKD4; Q9Z241; Q9Z242; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 09-DEC-2015, entry version 144. DE RecName: Full=Werner syndrome ATP-dependent helicase homolog; DE EC=3.6.4.12; DE AltName: Full=Exonuclease WRN; DE EC=3.1.-.-; GN Name=Wrn; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=BALB/cJ; TISSUE=Spleen, and Testis; RX PubMed=9143515; DOI=10.1006/geno.1997.4661; RA Imamura O., Ichikawa K., Yamabe Y., Goto M., Sugawara M., Furuichi Y.; RT "Cloning of a mouse homologue of the human Werner syndrome gene and RT assignment to 8A4 by fluorescence in situ hybridization."; RL Genomics 41:298-300(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RA Paeper B.W., Gayle M., Brady W., Swartz A., Gillett L.A., Alisch R.S., RA Mulligan J., Galas D., Fu Y.-H.; RT "Genomic structure of the human Werner's gene and cloning of its mouse RT homolog."; RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RC TISSUE=Lymph node, and Spleen; RX PubMed=10757812; DOI=10.1128/MCB.20.9.3286-3291.2000; RA Lombard D.B., Beard C., Johnson B., Marciniak R.A., Dausman J., RA Bronson R., Buhlmann J.E., Lipman R., Curry R., Sharpe A., RA Jaenisch R., Guarente L.; RT "Mutations in the WRN Gene in mice accelerate mortality in a p53-null RT background."; RL Mol. Cell. Biol. 20:3286-3291(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., RA She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., RA Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., RA Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J., RA Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., RA Lindblad-Toh K., Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of RT the mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP SUBCELLULAR LOCATION. RX PubMed=9618508; DOI=10.1073/pnas.95.12.6887; RA Marciniak R.A., Lombard D.B., Johnson F.B., Guarente L.; RT "Nucleolar localization of the Werner syndrome protein in human RT cells."; RL Proc. Natl. Acad. Sci. U.S.A. 95:6887-6892(1998). RN [7] RP INTERACTION WITH WRNIP1. RX PubMed=11301316; DOI=10.1074/jbc.C100035200; RA Kawabe Y., Branzei D., Hayashi T., Suzuki H., Masuko T., Onoda F., RA Heo S.-J., Ikeda H., Shimamoto A., Furuichi Y., Seki M., Enomoto T.; RT "A novel protein interacts with the Werner's syndrome gene product RT physically and functionally."; RL J. Biol. Chem. 276:20364-20369(2001). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and RT expression."; RL Cell 143:1174-1189(2010). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 31-238 IN COMPLEX WITH ZINC RP IONS AND SULFATE, SUBUNIT, FUNCTION, EXONUCLEASE ACTIVITY, ENZYME RP REGULATION, CIRCULAR DICHROISM, AND MUTAGENESIS OF LYS-185; ARG-190 RP AND TYR-206. RX PubMed=17229737; DOI=10.1074/jbc.M609657200; RA Choi J.M., Kang S.Y., Bae W.J., Jin K.S., Ree M., Cho Y.; RT "Probing the roles of active site residues in the 3'-5' exonuclease of RT the Werner syndrome protein."; RL J. Biol. Chem. 282:9941-9951(2007). CC -!- FUNCTION: Multifunctional enzyme that has both magnesium and ATP- CC dependent DNA-helicase activity and 3'->5' exonuclease activity CC towards double-stranded DNA with a 5'-overhang. Has no nuclease CC activity towards single-stranded DNA or blunt-ended double- CC stranded DNA. Binds preferentially to DNA substrates containing CC alternate secondary structures, such as replication forks and CC Holliday junctions. May play an important role in the dissociation CC of joint DNA molecules that can arise as products of homologous CC recombination, at stalled replication forks or during DNA repair. CC Alleviates stalling of DNA polymerases at the site of DNA lesions. CC Important for genomic integrity. Plays a role in the formation of CC DNA replication focal centers; stably associates with foci CC elements generating binding sites for RP-A (By similarity). Plays CC a role in double-strand break repair after gamma-irradiation (By CC similarity). {ECO:0000250, ECO:0000269|PubMed:10757812, CC ECO:0000269|PubMed:17229737}. CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Note=Binds 2 magnesium ions per subunit. Has high activity with CC manganese and zinc ions (in vitro).; CC -!- ENZYME REGULATION: Zinc ions stimulate the exonuclease activity. CC {ECO:0000269|PubMed:17229737}. CC -!- SUBUNIT: Monomer, and homooligomer. May exist as homodimer, CC homotrimer, homotetramer and/or homohexamer. Homotetramer, or CC homohexamer, when bound to DNA. Interacts via its N-terminal CC domain with WRNIP1. Interacts with PCNA; EXO1 and SUPV3L1 (By CC similarity). Interacts with PML (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9618508}. CC Nucleus, nucleolus {ECO:0000250}. Nucleus, nucleoplasm CC {ECO:0000250}. Note=Gamma-irradiation leads to its translocation CC from nucleoli to nucleoplasm and PML regulates the irradiation- CC induced WRN relocation. {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expressed ubiquitously in most organs at a low CC level, highly expressed in testis, ovary and spleen. CC {ECO:0000269|PubMed:10757812, ECO:0000269|PubMed:9143515}. CC -!- PTM: Phosphorylated by PRKDC. CC -!- SIMILARITY: Belongs to the helicase family. RecQ subfamily. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 3'-5' exonuclease domain. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 helicase ATP-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00541}. CC -!- SIMILARITY: Contains 1 helicase C-terminal domain. CC {ECO:0000255|PROSITE-ProRule:PRU00542}. CC -!- SIMILARITY: Contains 1 HRDC domain. {ECO:0000255|PROSITE- CC ProRule:PRU00328}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D86527; BAA20270.1; -; mRNA. DR EMBL; D86526; BAA20269.1; -; mRNA. DR EMBL; AF091215; AAC78077.1; -; mRNA. DR EMBL; AF091216; AAC72359.1; -; Genomic_DNA. DR EMBL; AF241636; AAF64490.1; -; mRNA. DR EMBL; AC153789; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC115809; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC050921; AAH50921.1; -; mRNA. DR EMBL; BC060700; AAH60700.1; -; mRNA. DR CCDS; CCDS22229.1; -. DR PIR; T17452; T17452. DR PIR; T30247; T30247. DR RefSeq; NP_001116294.1; NM_001122822.1. DR RefSeq; NP_035851.3; NM_011721.4. DR RefSeq; XP_006509154.1; XM_006509091.2. DR UniGene; Mm.228805; -. DR PDB; 2E6L; X-ray; 2.20 A; A=31-238. DR PDB; 2E6M; X-ray; 2.00 A; A=31-238. DR PDBsum; 2E6L; -. DR PDBsum; 2E6M; -. DR ProteinModelPortal; O09053; -. DR SMR; O09053; 37-225, 915-1058, 1107-1200. DR DIP; DIP-27642N; -. DR STRING; 10090.ENSMUSP00000033990; -. DR PhosphoSite; O09053; -. DR MaxQB; O09053; -. DR PaxDb; O09053; -. DR PRIDE; O09053; -. DR Ensembl; ENSMUST00000033990; ENSMUSP00000033990; ENSMUSG00000031583. DR Ensembl; ENSMUST00000033991; ENSMUSP00000033991; ENSMUSG00000031583. DR GeneID; 22427; -. DR KEGG; mmu:22427; -. DR UCSC; uc009ljw.1; mouse. DR CTD; 7486; -. DR MGI; MGI:109635; Wrn. DR eggNOG; KOG0351; Eukaryota. DR eggNOG; KOG4373; Eukaryota. DR eggNOG; COG0514; LUCA. DR GeneTree; ENSGT00550000074520; -. DR HOGENOM; HOG000146447; -. DR HOVERGEN; HBG000325; -. DR InParanoid; O09053; -. DR KO; K10900; -. DR OMA; YLIHMAI; -. DR OrthoDB; EOG7J70F2; -. DR TreeFam; TF312852; -. DR Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA). DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-MMU-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-MMU-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-MMU-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends. DR Reactome; R-MMU-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR EvolutionaryTrace; O09053; -. DR NextBio; 302865; -. DR PRO; PR:O09053; -. DR Proteomes; UP000000589; Chromosome 8. DR Bgee; O09053; -. DR CleanEx; MM_WRN; -. DR Genevisible; O09053; MM. DR GO; GO:0005813; C:centrosome; ISO:MGI. DR GO; GO:0032389; C:MutLalpha complex; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0043138; F:3'-5' DNA helicase activity; ISO:MGI. DR GO; GO:0008408; F:3'-5' exonuclease activity; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0043140; F:ATP-dependent 3'-5' DNA helicase activity; IEA:InterPro. DR GO; GO:0004003; F:ATP-dependent DNA helicase activity; ISO:MGI. DR GO; GO:0016887; F:ATPase activity; ISO:MGI. DR GO; GO:0000405; F:bubble DNA binding; ISO:MGI. DR GO; GO:0003677; F:DNA binding; ISO:MGI. DR GO; GO:0003678; F:DNA helicase activity; ISO:MGI. DR GO; GO:0004527; F:exonuclease activity; ISO:MGI. DR GO; GO:0009378; F:four-way junction helicase activity; ISO:MGI. DR GO; GO:0051880; F:G-quadruplex DNA binding; ISO:MGI. DR GO; GO:0004386; F:helicase activity; ISO:MGI. DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB. DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB. DR GO; GO:0032403; F:protein complex binding; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI. DR GO; GO:0000403; F:Y-form DNA binding; ISO:MGI. DR GO; GO:0006284; P:base-excision repair; ISO:MGI. DR GO; GO:0007569; P:cell aging; ISO:MGI. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI. DR GO; GO:0071480; P:cellular response to gamma radiation; ISS:UniProtKB. DR GO; GO:0009267; P:cellular response to starvation; ISO:MGI. DR GO; GO:0032508; P:DNA duplex unwinding; ISO:MGI. DR GO; GO:0006259; P:DNA metabolic process; ISS:UniProtKB. DR GO; GO:0006310; P:DNA recombination; IEA:InterPro. DR GO; GO:0006260; P:DNA replication; IMP:MGI. DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISO:MGI. DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB. DR GO; GO:0010259; P:multicellular organismal aging; IGI:MGI. DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; ISO:MGI. DR GO; GO:0032066; P:nucleolus to nucleoplasm transport; ISO:MGI. DR GO; GO:0051345; P:positive regulation of hydrolase activity; ISO:MGI. DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI. DR GO; GO:0040009; P:regulation of growth rate; IMP:MGI. DR GO; GO:0031297; P:replication fork processing; ISO:MGI. DR GO; GO:0001302; P:replicative cell aging; IMP:MGI. DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI. DR GO; GO:0010225; P:response to UV-C; ISO:MGI. DR GO; GO:0000723; P:telomere maintenance; IMP:MGI. DR Gene3D; 1.10.10.10; -; 1. DR Gene3D; 1.10.150.80; -; 1. DR Gene3D; 3.30.420.10; -; 1. DR Gene3D; 3.40.50.300; -; 2. DR InterPro; IPR002562; 3'-5'_exonuclease_dom. DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom. DR InterPro; IPR004589; DNA_helicase_ATP-dep_RecQ. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C. DR InterPro; IPR029491; Helicase_HTH. DR InterPro; IPR010997; HRDC-like. DR InterPro; IPR002121; HRDC_dom. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR032284; RecQ_Zn-bd. DR InterPro; IPR012337; RNaseH-like_dom. DR InterPro; IPR018982; RQC_domain. DR InterPro; IPR011991; WHTH_DNA-bd_dom. DR Pfam; PF00270; DEAD; 1. DR Pfam; PF01612; DNA_pol_A_exo1; 1. DR Pfam; PF00271; Helicase_C; 1. DR Pfam; PF00570; HRDC; 1. DR Pfam; PF14493; HTH_40; 1. DR Pfam; PF16124; RecQ_Zn_bind; 1. DR Pfam; PF09382; RQC; 1. DR SMART; SM00474; 35EXOc; 1. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00490; HELICc; 1. DR SMART; SM00341; HRDC; 1. DR SMART; SM00956; RQC; 1. DR SUPFAM; SSF46785; SSF46785; 1. DR SUPFAM; SSF47819; SSF47819; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR SUPFAM; SSF53098; SSF53098; 1. DR TIGRFAMs; TIGR00614; recQ_fam; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS50967; HRDC; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Complete proteome; DNA damage; DNA repair; KW DNA-binding; Exonuclease; Helicase; Hydrolase; Magnesium; KW Metal-binding; Multifunctional enzyme; Nuclease; Nucleotide-binding; KW Nucleus; Phosphoprotein; Reference proteome; Zinc. FT CHAIN 1 1401 Werner syndrome ATP-dependent helicase FT homolog. FT /FTId=PRO_0000205046. FT DOMAIN 51 223 3'-5' exonuclease. FT DOMAIN 522 688 Helicase ATP-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00541}. FT DOMAIN 713 866 Helicase C-terminal. FT {ECO:0000255|PROSITE-ProRule:PRU00542}. FT DOMAIN 1115 1194 HRDC. {ECO:0000255|PROSITE- FT ProRule:PRU00328}. FT NP_BIND 535 542 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00541}. FT REGION 1 271 Interaction with WRNIP1. FT REGION 952 958 Interaction with DNA. {ECO:0000250}. FT MOTIF 632 635 DEAH box. FT COMPBIAS 1387 1390 Poly-Ser. FT METAL 76 76 Magnesium 1; catalytic. FT METAL 76 76 Magnesium 2; catalytic. FT METAL 78 78 Magnesium 1; catalytic. FT METAL 210 210 Magnesium 1; catalytic. FT SITE 139 139 Interaction with DNA. {ECO:0000250}. FT SITE 1002 1002 Interaction with DNA. {ECO:0000250}. FT MOD_RES 419 419 Phosphoserine. FT {ECO:0000250|UniProtKB:Q14191}. FT MOD_RES 433 433 Phosphoserine. FT {ECO:0000250|UniProtKB:Q14191}. FT MOD_RES 1098 1098 Phosphoserine. FT {ECO:0000250|UniProtKB:Q14191}. FT MUTAGEN 185 185 K->A: Loss of exonuclease activity. FT {ECO:0000269|PubMed:17229737}. FT MUTAGEN 190 190 R->A: Strongly reduced exonuclease FT activity. {ECO:0000269|PubMed:17229737}. FT MUTAGEN 206 206 Y->F: Loss of exonuclease activity. FT {ECO:0000269|PubMed:17229737}. FT CONFLICT 101 101 S -> N (in Ref. 1; BAA20269/BAA20270, 2; FT AAC72359 and 3; AAF64490). {ECO:0000305}. FT CONFLICT 228 228 A -> V (in Ref. 1; BAA20269/BAA20270, 2; FT AAC72359 and 3; AAF64490). {ECO:0000305}. FT CONFLICT 250 250 S -> L (in Ref. 1; BAA20269/BAA20270, 2; FT AAC72359 and 3; AAF64490). {ECO:0000305}. FT CONFLICT 452 452 V -> M (in Ref. 1; BAA20269/BAA20270, 2; FT AAC72359 and 3; AAF64490). {ECO:0000305}. FT CONFLICT 459 459 T -> K (in Ref. 1; BAA20269/BAA20270, 2; FT AAC72359 and 3; AAF64490). {ECO:0000305}. FT CONFLICT 468 468 R -> C (in Ref. 1; BAA20269/BAA20270, 2; FT AAC72359 and 3; AAF64490). {ECO:0000305}. FT CONFLICT 619 619 Q -> K (in Ref. 1; BAA20269/BAA20270, 2; FT AAC72359 and 3; AAF64490). {ECO:0000305}. FT CONFLICT 800 800 K -> Q (in Ref. 1; BAA20270/BAA20269). FT {ECO:0000305}. FT CONFLICT 844 844 L -> H (in Ref. 2; AAC72359). FT {ECO:0000305}. FT CONFLICT 955 988 NSQRLPDKYRGHRLFGAGKEQAESWWKTLSHHLI -> VSV FT SVIAPGTVSDSAFHCVAMALAFFRWLTSNPC (in Ref. FT 2; AAC72359). {ECO:0000305}. FT CONFLICT 1021 1021 S -> L (in Ref. 1; BAA20269/BAA20270 and FT 3; AAF64490). {ECO:0000305}. FT CONFLICT 1145 1145 T -> A (in Ref. 1; BAA20270/BAA20269). FT {ECO:0000305}. FT CONFLICT 1181 1181 L -> V (in Ref. 1; BAA20270/BAA20269). FT {ECO:0000305}. FT CONFLICT 1182 1182 E -> G (in Ref. 1; BAA20269/BAA20270 and FT 3; AAF64490). {ECO:0000305}. FT CONFLICT 1252 1252 A -> V (in Ref. 1; BAA20269/BAA20270 and FT 3; AAF64490). {ECO:0000305}. FT CONFLICT 1308 1308 L -> I (in Ref. 1; BAA20269/BAA20270 and FT 3; AAF64490). {ECO:0000305}. FT CONFLICT 1356 1356 A -> V (in Ref. 1; BAA20269/BAA20270 and FT 3; AAF64490). {ECO:0000305}. FT STRAND 45 50 FT HELIX 53 66 FT STRAND 72 78 FT STRAND 93 97 FT STRAND 99 106 FT HELIX 108 110 FT HELIX 116 122 FT STRAND 127 133 FT HELIX 134 145 FT STRAND 151 154 FT HELIX 155 162 FT HELIX 171 179 FT HELIX 187 190 FT STRAND 196 198 FT HELIX 201 222 SQ SEQUENCE 1401 AA; 157204 MW; 66DF2252B17C24C3 CRC64; METTSLQRKF PEWMSMQSQR CATEEKACVQ KSVLEDNLPF LEFPGSIVYS YEASDCSFLS EDISMRLSDG DVVGFDMEWP PIYKPGKRSR VAVIQLCVSE SKCYLFHISS MSVFPQGLKM LLENKSIKKA GVGIEGDQWK LLRDFDVKLE SFVELTDVAN EKLKCAETWS LNGLVKHVLG KQLLKDKSIR CSNWSNFPLT EDQKLYAATD AYAGLIIYQK LGNLGDTAQV FALNKAEENL PLEMKKQLNS ISEEMRDLAN RFPVTCRNLE TLQRVPVILK SISENLCSLR KVICGPTNTE TRLKPGSSFN LLSSEDSAAA GEKEKQIGKH STFAKIKEEP WDPELDSLVK QEEVDVFRNQ VKQEKGESEN EIEDNLLRED MERTCVIPSI SENELQDLEQ QAKEEKYNDV SHQLSEHLSP NDDENDSSYI IESDEDLEME MLKSLENLNS DVVEPTHSTW LEMGTNGRLP PEEEDGHGNE AIKEEQEEED HLLPEPNAKQ INCLKTYFGH SSFKPVQWKV IHSVLEERRD NVVVMATGYG KSLCFQYPPV YTGKIGIVIS PLISLMEDQV LQLELSNVPA CLLGSAQSKN ILGDVKLGKY RVIYITPEFC SGNLDLLQQL DSSIGITLIA VDEAHCISEW GHDFRSSFRM LGSLKTALPL VPVIALSATA SSSIREDIIS CLNLKDPQIT CTGFDRPNLY LEVGRKTGNI LQDLKPFLVR KASSAWEFEG PTIIYCPSRK MTEQVTAELG KLNLACRTYH AGMKISERKD VHHRFLRDEI QCVVATVAFG MGINKADIRK VIHYGAPKEM ESYYQEIGRA GRDGLQSSCH LLWAPADFNT SRNLLIEIHD EKFRLYKLKM MVKMEKYLHS SQCRRRIILS HFEDKCLQKA SLDIMGTEKC CDNCRPRLNH CLTANNSEDA SQDFGPQAFQ LLSAVDILQE KFGIGIPILF LRGSNSQRLP DKYRGHRLFG AGKEQAESWW KTLSHHLIAE GFLVEVPKEN KYIKTCSLTK KGRKWLGEAS SQSPPSLLLQ ANEEMFPRKV LLPSSNPVSP ETTQHSSNQN PAGLTTKQSN LERTHSYKVP EKVSSGTNIP KKSAVMPSPG TSSSPLEPAI SAQELDARTG LYARLVEARQ KHANKMDVPP AILATNKVLL DMAKMRPTTV ENMKQIDGVS EGKAALLAPL LEVIKHFCQV TSVQTDLLSS AKPHKEQEKS QEMEKKDCSL PQSVAVTYTL FQEKKMPLHS IAENRLLPLT AAGMHLAQAV KAGYPLDMER AGLTPETWKI IMDVIRNPPI NSDMYKVKLI RMLVPENLDT YLIHMAIEIL QSGSDSRTQP PCDSSRKRRF PSSAESCESC KESKEAVTET KASSSESKRK LPEWFAKGNV PSADTGSSSS MAKTKKKGLF S //