ID WRN_HUMAN Reviewed; 1432 AA. AC Q14191; A1KYY9; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 08-FEB-2011, sequence version 2. DT 11-NOV-2015, entry version 180. DE RecName: Full=Werner syndrome ATP-dependent helicase; DE EC=3.6.4.12; DE AltName: Full=DNA helicase, RecQ-like type 3; DE Short=RecQ3; DE AltName: Full=Exonuclease WRN; DE EC=3.1.-.-; DE AltName: Full=RecQ protein-like 2; GN Name=WRN; Synonyms=RECQ3, RECQL2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PHE-1074. RX PubMed=8602509; DOI=10.1126/science.272.5259.258; RA Yu C.-E., Oshima J., Fu Y.-H., Wijsman E.M., Hisama F., Alisch R., RA Matthews S., Nakura J., Miki T., Ouais S., Martin G.M., Mulligan J., RA Schellenberg G.D.; RT "Positional cloning of the Werner's syndrome gene."; RL Science 272:258-262(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PHE-1074. RX PubMed=16723399; DOI=10.1073/pnas.0600645103; RA Agrelo R., Cheng W.H., Setien F., Ropero S., Espada J., Fraga M.F., RA Herranz M., Paz M.F., Sanchez-Cespedes M., Artiga M.J., Guerrero D., RA Castells A., von Kobbe C., Bohr V.A., Esteller M.; RT "Epigenetic inactivation of the premature aging Werner syndrome gene RT in human cancer."; RL Proc. Natl. Acad. Sci. U.S.A. 103:8822-8827(2006). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PHE-1074. 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 the mouse RT homolog."; RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-114; LYS-343; RP ILE-387; SER-533; CYS-612; PHE-708; CYS-834; SER-912; LEU-1079; RP ALA-1133; ILE-1339 AND ARG-1367. RG NIEHS SNPs program; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T., RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., RA Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). 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 REPEATS. RX PubMed=10049920; RA Kusano K., Berres M.E., Engels W.R.; RT "Evolution of the RECQ family of helicases: a Drosophila homolog, RT Dmblm, is similar to the human Bloom syndrome gene."; RL Genetics 151:1027-1039(1999). RN [8] RP FUNCTION, MUTAGENESIS OF GLU-84, FUNCTION AS AN EXONUCLEASE, RP DNA-BINDING, INTERACTION WITH PCNA, AND SUBUNIT. RX PubMed=11863428; DOI=10.1021/bi0157161; RA Xue Y., Ratcliff G.C., Wang H., Davis-Searles P.R., Gray M.D., RA Erie D.A., Redinbo M.R.; RT "A minimal exonuclease domain of WRN forms a hexamer on DNA and RT possesses both 3'- 5' exonuclease and 5'-protruding strand RT endonuclease activities."; RL Biochemistry 41:2901-2912(2002). RN [9] RP PHOSPHORYLATION. RX PubMed=11889123; DOI=10.1074/jbc.M111523200; RA Karmakar P., Piotrowski J., Brosh R.M. Jr., Sommers J.A., Miller S.P., RA Cheng W.H., Snowden C.M., Ramsden D.A., Bohr V.A.; RT "Werner protein is a target of DNA-dependent protein kinase in vivo RT and in vitro, and its catalytic activities are regulated by RT phosphorylation."; RL J. Biol. Chem. 277:18291-18302(2002). RN [10] RP INTERACTION WITH EXO1. RX PubMed=12704184; DOI=10.1074/jbc.M212798200; RA Sharma S., Sommers J.A., Driscoll H.C., Uzdilla L.A., Wilson T.M., RA Brosh R.M. Jr.; RT "The exonucleolytic and endonucleolytic cleavage activities of human RT exonuclease 1 are stimulated by an interaction with the carboxyl- RT terminal region of the Werner syndrome protein."; RL J. Biol. Chem. 278:23487-23496(2003). RN [11] RP INTERACTION WITH SUPV3L1. RX PubMed=17961633; DOI=10.1016/j.mad.2007.09.001; RA Pereira M., Mason P., Szczesny R.J., Maddukuri L., Dziwura S., RA Jedrzejczak R., Paul E., Wojcik A., Dybczynska L., Tudek B., RA Bartnik E., Klysik J., Bohr V.A., Stepien P.P.; RT "Interaction of human SUV3 RNA/DNA helicase with BLM helicase; loss of RT the SUV3 gene results in mouse embryonic lethality."; RL Mech. Ageing Dev. 128:609-617(2007). RN [12] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17563354; DOI=10.1073/pnas.0702513104; RA Kamath-Loeb A.S., Lan L., Nakajima S., Yasui A., Loeb L.A.; RT "Werner syndrome protein interacts functionally with translesion DNA RT polymerases."; RL Proc. Natl. Acad. Sci. U.S.A. 104:10394-10399(2007). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [14] RP FUNCTION, SUBUNIT, AND DNA-BINDING. RX PubMed=18596042; DOI=10.1074/jbc.M803370200; RA Compton S.A., Tolun G., Kamath-Loeb A.S., Loeb L.A., Griffith J.D.; RT "The Werner syndrome protein binds replication fork and Holliday RT junction DNAs as an oligomer."; RL J. Biol. Chem. 283:24478-24483(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-440 AND SER-467, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [17] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19652551; DOI=10.4161/cc.8.17.9410; RA Zecevic A., Menard H., Gurel V., Hagan E., DeCaro R., Zhitkovich A.; RT "WRN helicase promotes repair of DNA double-strand breaks caused by RT aberrant mismatch repair of chromium-DNA adducts."; RL Cell Cycle 8:2769-2778(2009). RN [18] RP FUNCTION. RX PubMed=19283071; DOI=10.1371/journal.pone.0004825; RA Opresko P.L., Sowd G., Wang H.; RT "The Werner syndrome helicase/exonuclease processes mobile D-loops RT through branch migration and degradation."; RL PLoS ONE 4:E4825-E4825(2009). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-426; SER-440; SER-453 RP AND SER-467, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PML. RX PubMed=21639834; DOI=10.1134/S000629791105004X; RA Liu J., Song Y., Qian J., Liu B., Dong Y., Tian B., Sun Z.; RT "Promyelocytic leukemia protein interacts with werner syndrome RT helicase and regulates double-strand break repair in gamma- RT irradiation-induced DNA damage responses."; RL Biochemistry (Mosc.) 76:550-554(2011). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1133, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [23] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [24] RP STRUCTURE BY NMR OF 949-1092. RX PubMed=16339893; DOI=10.1073/pnas.0509380102; RA Hu J.S., Feng H., Zeng W., Lin G.X., Xi X.G.; RT "Solution structure of a multifunctional DNA- and protein-binding RT motif of human Werner syndrome protein."; RL Proc. Natl. Acad. Sci. U.S.A. 102:18379-18384(2005). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 38-236 IN COMPLEXES WITH RP MAGNESIUM; MANGANESE; EUROPIUM AND GMP, PARTIAL PROTEIN SEQUENCE, RP IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, COFACTOR, RP MUTAGENESIS OF GLU-84; TRP-145 AND TYR-212, AND CHARACTERIZATION OF RP VARIANTS ILE-114 AND PRO-172. RX PubMed=16622405; DOI=10.1038/nsmb1088; RA Perry J.J., Yannone S.M., Holden L.G., Hitomi C., Asaithamby A., RA Han S., Cooper P.K., Chen D.J., Tainer J.A.; RT "WRN exonuclease structure and molecular mechanism imply an editing RT role in DNA end processing."; RL Nat. Struct. Mol. Biol. 13:414-422(2006). RN [26] RP REVIEW ON VARIANTS. RX PubMed=10220139; RX DOI=10.1002/(SICI)1098-1004(1999)13:4<271::AID-HUMU2>3.0.CO;2-Q; RA Moser M.J., Oshima J., Monnat R.J. Jr.; RT "WRN mutations in Werner syndrome."; RL Hum. Mutat. 13:271-279(1999). RN [27] RP STRUCTURE BY NMR OF 1140-1239. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the helicase and RNase D C-terminal domain in RT Werner syndrome ATP-dependent helicase."; RL Submitted (SEP-2006) to the PDB data bank. RN [28] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1142-1242, PARTIAL PROTEIN RP SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, AND CIRCULAR DICHROISM. RX PubMed=17148451; DOI=10.1074/jbc.M610142200; RA Kitano K., Yoshihara N., Hakoshima T.; RT "Crystal structure of the HRDC domain of human Werner syndrome RT protein, WRN."; RL J. Biol. Chem. 282:2717-2728(2007). RN [29] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 949-1079 IN COMPLEX WITH RP DOUBLE-STRANDED DNA, INTERACTION WITH DNA, AND MUTAGENESIS OF ARG-987; RP SER-989; ARG-993; PHE-1037 AND MET-1038. RX PubMed=20159463; DOI=10.1016/j.str.2009.12.011; RA Kitano K., Kim S.Y., Hakoshima T.; RT "Structural basis for DNA strand separation by the unconventional RT winged-helix domain of RecQ helicase WRN."; RL Structure 18:177-187(2010). RN [30] RP VARIANT ARG-1367. RX PubMed=9021029; RX DOI=10.1002/(SICI)1096-8628(19970211)68:4<494::AID-AJMG30>3.0.CO;2-L; RA Ye L., Miki T., Nakura J., Oshima J., Kamino K., Rakugi H., RA Ikegami H., Higaki J., Edland S.D., Martin G.M., Ogihara T.; RT "Association of a polymorphic variant of the Werner helicase gene with RT myocardial infarction in a Japanese population."; RL Am. J. Med. Genet. 68:494-498(1997). RN [31] RP ERRATUM. RA Ye L., Miki T., Nakura J., Oshima J., Kamino K., Rakugi H., RA Ikegami H., Higaki J., Edland S.D., Martin G.M., Ogihara T.; RL Am. J. Med. Genet. 70:103-103(1997). RN [32] RP VARIANTS ILE-387 AND PHE-1074. RX PubMed=9450180; RA Meisslitzer C., Ruppitsch W., Weirich-Schwaiger H., Weirich H.G., RA Jabkowsky J., Klein G., Schweiger M., Hirsch-Kauffmann M.; RT "Werner syndrome: characterization of mutations in the WRN gene in an RT affected family."; RL Eur. J. Hum. Genet. 5:364-370(1997). RN [33] RP VARIANT ILE-387. RX PubMed=10206685; RX DOI=10.1002/(SICI)1098-1004(1998)11:5<413::AID-HUMU18>3.0.CO;2-C; RA Vidal V., Bay J.-O., Champomier F., Grancho M., Beauville L., RA Glowaczower C., Lemery D., Ferrara M., Bignon Y.-J.; RT "The 1396del A mutation and a missense mutation or a rare polymorphism RT of the WRN gene detected in a French Werner family with a severe RT phenotype and a case of an unusual vulvar cancer."; RL Hum. Mutat. 11:413-414(1998). RN [34] RP VARIANTS ALA-324 AND ARG-1367. RX PubMed=10069711; RX DOI=10.1002/(SICI)1096-8628(19990219)82:5<399::AID-AJMG8>3.3.CO;2-I; RA Castro E., Ogburn C.E., Hunt K.E., Tilvis R., Louhija J., RA Penttinen R., Erkkola R., Panduro A., Riestra R., Piussan C., RA Deeb S.S., Wang L., Edland S.D., Martin G.M., Oshima J.; RT "Polymorphisms at the Werner locus: I. Newly identified polymorphisms, RT ethnic variability of 1367Cys/Arg, and its stability in a population RT of Finnish centenarians."; RL Am. J. Med. Genet. 82:399-403(1999). RN [35] RP VARIANTS ARG-32; ILE-114; PRO-172; LYS-240; TRP-383; ILE-387; LEU-724; RP PHE-1074; GLU-1269 AND ARG-1367. RX PubMed=11161804; DOI=10.1006/geno.2000.6405; RA Passarino G., Shen P., Van Kirk J.B., Lin A.A., De Benedictis G., RA Cavalli-Sforza L.L., Oefner P.J., Underhill P.A.; RT "The Werner syndrome gene and global sequence variation."; RL Genomics 71:118-122(2001). RN [36] RP VARIANTS WRN ASN-125 AND GLU-135. RX PubMed=16673358; DOI=10.1002/humu.20337; RA Huang S., Lee L., Hanson N.B., Lenaerts C., Hoehn H., Poot M., RA Rubin C.D., Chen D.-F., Yang C.-C., Juch H., Dorn T., Spiegel R., RA Oral E.A., Abid M., Battisti C., Lucci-Cordisco E., Neri G., RA Steed E.H., Kidd A., Isley W., Showalter D., Vittone J.L., RA Konstantinow A., Ring J., Meyer P., Wenger S.L., Herbay A.V., RA Wollina U., Schuelke M., Huizenga C.R., Leistritz D.F., Martin G.M., RA Mian I.S., Oshima J.; RT "The spectrum of WRN mutations in Werner syndrome patients."; RL Hum. Mutat. 27:558-567(2006). RN [37] RP VARIANT [LARGE SCALE ANALYSIS] VAL-92. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). RN [38] RP VARIANT [LARGE SCALE ANALYSIS] LEU-1141. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., RA Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., RA Graubert T.A., DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). 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. CC {ECO:0000250, ECO:0000269|PubMed:11863428, CC ECO:0000269|PubMed:17563354, ECO:0000269|PubMed:18596042, CC ECO:0000269|PubMed:19283071, ECO:0000269|PubMed:19652551, CC ECO:0000269|PubMed:21639834}. CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. CC {ECO:0000269|PubMed:16622405}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:16622405}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:16622405}; CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:16622405}; CC Note=Binds 2 magnesium ions per subunit. Has high activity with CC manganese and zinc ions (in vitro). {ECO:0000269|PubMed:16622405}; 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 (By similarity). Interacts with EXO1, PCNA and CC SUPV3L1. Interacts with PML (isoform PML-4). {ECO:0000250, CC ECO:0000269|PubMed:11863428, ECO:0000269|PubMed:12704184, CC ECO:0000269|PubMed:17961633, ECO:0000269|PubMed:18596042, CC ECO:0000269|PubMed:20159463, ECO:0000269|PubMed:21639834}. CC -!- INTERACTION: CC P54132:BLM; NbExp=9; IntAct=EBI-368417, EBI-621372; CC P39748:FEN1; NbExp=9; IntAct=EBI-368417, EBI-707816; CC P09874:PARP1; NbExp=8; IntAct=EBI-368417, EBI-355676; CC P43351:RAD52; NbExp=9; IntAct=EBI-368417, EBI-706448; CC P27694:RPA1; NbExp=9; IntAct=EBI-368417, EBI-621389; CC Q96EB6:SIRT1; NbExp=9; IntAct=EBI-368417, EBI-1802965; CC Q15554:TERF2; NbExp=8; IntAct=EBI-368417, EBI-706637; CC P04637:TP53; NbExp=5; IntAct=EBI-368417, EBI-366083; CC P12956:XRCC6; NbExp=4; IntAct=EBI-368417, EBI-353208; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus. Nucleus. Nucleus, CC nucleoplasm. Note=Gamma-irradiation leads to its translocation CC from nucleoli to nucleoplasm and PML regulates the irradiation- CC induced WRN relocation. CC -!- PTM: Phosphorylated by PRKDC. {ECO:0000269|PubMed:11889123}. CC -!- DISEASE: Werner syndrome (WRN) [MIM:277700]: A rare autosomal CC recessive progeroid syndrome characterized by the premature onset CC of multiple age-related disorders, including atherosclerosis, CC cancer, non-insulin-dependent diabetes mellitus, ocular cataracts CC and osteoporosis. The major cause of death, at a median age of 47, CC is myocardial infarction. {ECO:0000269|PubMed:16673358}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease CC characterized by malignant lesions arising from the inner wall of CC the large intestine (the colon) and the rectum. Genetic CC alterations are often associated with progression from CC premalignant lesion (adenoma) to invasive adenocarcinoma. Risk CC factors for cancer of the colon and rectum include colon polyps, CC long-standing ulcerative colitis, and genetic family history. CC Note=The disease may be caused by mutations affecting the gene CC represented in this entry. 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 -!- WEB RESOURCE: Name=WRN; Note=WRN mutation db (Warner disease); CC URL="http://www.pathology.washington.edu/werner/ws_wrn.html"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/WRNID284.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/wrn/"; 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; L76937; AAC41981.1; -; Genomic_DNA. DR EMBL; AY818673; AAX21098.1; -; mRNA. DR EMBL; AF091214; AAC63361.1; -; mRNA. DR EMBL; AF181897; AAF06162.1; -; Genomic_DNA. DR EMBL; AF181896; AAF06162.1; JOINED; Genomic_DNA. DR EMBL; AY442327; AAR05448.1; -; Genomic_DNA. DR EMBL; AC084736; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS6082.1; -. DR RefSeq; NP_000544.2; NM_000553.4. DR UniGene; Hs.632050; -. DR PDB; 2AXL; NMR; -; A=949-1092. DR PDB; 2DGZ; NMR; -; A=1140-1239. DR PDB; 2E1E; X-ray; 2.30 A; A=1142-1242. DR PDB; 2E1F; X-ray; 2.00 A; A=1142-1242. DR PDB; 2FBT; X-ray; 2.05 A; A=38-236. DR PDB; 2FBV; X-ray; 2.40 A; A=38-236. DR PDB; 2FBX; X-ray; 2.20 A; A=38-236. DR PDB; 2FBY; X-ray; 2.00 A; A=38-236. DR PDB; 2FC0; X-ray; 2.00 A; A=38-236. DR PDB; 3AAF; X-ray; 1.90 A; A/B=949-1079. DR PDBsum; 2AXL; -. DR PDBsum; 2DGZ; -. DR PDBsum; 2E1E; -. DR PDBsum; 2E1F; -. DR PDBsum; 2FBT; -. DR PDBsum; 2FBV; -. DR PDBsum; 2FBX; -. DR PDBsum; 2FBY; -. DR PDBsum; 2FC0; -. DR PDBsum; 3AAF; -. DR DisProt; DP00443; -. DR ProteinModelPortal; Q14191; -. DR SMR; Q14191; 38-231, 540-1092, 1142-1235. DR BioGrid; 113323; 44. DR DIP; DIP-31380N; -. DR IntAct; Q14191; 21. DR MINT; MINT-95856; -. DR STRING; 9606.ENSP00000298139; -. DR BindingDB; Q14191; -. DR ChEMBL; CHEMBL2146312; -. DR PhosphoSite; Q14191; -. DR BioMuta; WRN; -. DR DMDM; 322510082; -. DR MaxQB; Q14191; -. DR PaxDb; Q14191; -. DR PRIDE; Q14191; -. DR Ensembl; ENST00000298139; ENSP00000298139; ENSG00000165392. DR GeneID; 7486; -. DR KEGG; hsa:7486; -. DR UCSC; uc003xio.4; human. DR CTD; 7486; -. DR GeneCards; WRN; -. DR GeneReviews; WRN; -. DR H-InvDB; HIX0007441; -. DR HGNC; HGNC:12791; WRN. DR HPA; HPA028661; -. DR MIM; 114500; phenotype. DR MIM; 277700; phenotype. DR MIM; 604611; gene. DR neXtProt; NX_Q14191; -. DR Orphanet; 902; Werner syndrome. DR PharmGKB; PA367; -. DR eggNOG; KOG0351; Eukaryota. DR eggNOG; KOG4373; Eukaryota. DR eggNOG; COG0514; LUCA. DR GeneTree; ENSGT00550000074520; -. DR HOGENOM; HOG000146447; -. DR HOVERGEN; HBG000325; -. DR InParanoid; Q14191; -. DR KO; K10900; -. DR OMA; YLIHMAI; -. DR OrthoDB; EOG7J70F2; -. DR PhylomeDB; Q14191; -. DR TreeFam; TF312852; -. DR BRENDA; 3.6.4.12; 2681. DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. DR ChiTaRS; WRN; human. DR EvolutionaryTrace; Q14191; -. DR GeneWiki; Werner_syndrome_ATP-dependent_helicase; -. DR GenomeRNAi; 7486; -. DR NextBio; 29326; -. DR PRO; PR:Q14191; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; Q14191; -. DR CleanEx; HS_WRN; -. DR Genevisible; Q14191; HS. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0043138; F:3'-5' DNA helicase activity; IDA:UniProtKB. DR GO; GO:0008408; F:3'-5' exonuclease activity; IDA: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; IDA:UniProtKB. DR GO; GO:0016887; F:ATPase activity; IDA:UniProtKB. DR GO; GO:0000405; F:bubble DNA binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0003678; F:DNA helicase activity; IMP:UniProtKB. DR GO; GO:0004527; F:exonuclease activity; IDA:MGI. DR GO; GO:0009378; F:four-way junction helicase activity; IDA:UniProtKB. DR GO; GO:0051880; F:G-quadruplex DNA binding; IDA:UniProtKB. DR GO; GO:0004386; F:helicase activity; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB. DR GO; GO:0032403; F:protein complex binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0000403; F:Y-form DNA binding; IDA:UniProtKB. DR GO; GO:0007568; P:aging; NAS:UniProtKB. DR GO; GO:0006284; P:base-excision repair; IDA:UniProtKB. DR GO; GO:0007569; P:cell aging; IMP:UniProtKB. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB. DR GO; GO:0071480; P:cellular response to gamma radiation; IDA:UniProtKB. DR GO; GO:0009267; P:cellular response to starvation; IDA:MGI. DR GO; GO:0032508; P:DNA duplex unwinding; IDA:GOC. DR GO; GO:0006259; P:DNA metabolic process; IDA:UniProtKB. DR GO; GO:0006310; P:DNA recombination; IEA:InterPro. DR GO; GO:0006260; P:DNA replication; IMP:UniProtKB. DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; IDA:UniProtKB. DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB. DR GO; GO:0010259; P:multicellular organismal aging; IMP:UniProtKB. DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IDA:GOC. DR GO; GO:0032066; P:nucleolus to nucleoplasm transport; IDA:MGI. DR GO; GO:0051345; P:positive regulation of hydrolase activity; IDA:UniProtKB. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0016925; P:protein sumoylation; TAS:Reactome. DR GO; GO:0042981; P:regulation of apoptotic process; IGI:MGI. DR GO; GO:0040009; P:regulation of growth rate; IEA:Ensembl. DR GO; GO:0031297; P:replication fork processing; IDA:UniProtKB. DR GO; GO:0001302; P:replicative cell aging; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB. DR GO; GO:0010225; P:response to UV-C; IDA:UniProtKB. DR GO; GO:0000723; P:telomere maintenance; IMP:UniProtKB. 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; 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; Acetylation; ATP-binding; Complete proteome; KW Direct protein sequencing; Disease mutation; DNA damage; DNA repair; KW DNA-binding; Exonuclease; Helicase; Hydrolase; Magnesium; KW Metal-binding; Multifunctional enzyme; Nuclease; Nucleotide-binding; KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; KW Zinc. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:22814378}. FT CHAIN 2 1432 Werner syndrome ATP-dependent helicase. FT /FTId=PRO_0000205045. FT DOMAIN 60 228 3'-5' exonuclease. FT REPEAT 424 450 1. {ECO:0000269|PubMed:10049920}. FT REPEAT 451 477 2. {ECO:0000269|PubMed:10049920}. FT DOMAIN 558 724 Helicase ATP-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00541}. FT DOMAIN 749 899 Helicase C-terminal. FT {ECO:0000255|PROSITE-ProRule:PRU00542}. FT DOMAIN 1150 1229 HRDC. {ECO:0000255|PROSITE- FT ProRule:PRU00328}. FT NP_BIND 571 578 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00541}. FT REGION 2 277 Interaction with WRNIP1. {ECO:0000250}. FT REGION 424 477 2 X 27 AA tandem repeats of H-L-S-P-N-D- FT N-E-N-D-T-S-Y-V-I-E-S-D-E-D-L-E-M-E-M-L- FT K. FT REGION 987 993 Interaction with DNA. FT MOTIF 668 671 DEAH box. FT COMPBIAS 507 510 Poly-Glu. FT METAL 82 82 Magnesium 1; catalytic. FT METAL 82 82 Magnesium 2; catalytic. FT METAL 84 84 Magnesium 1; catalytic. FT METAL 216 216 Magnesium 1; catalytic. FT SITE 145 145 Interaction with DNA. {ECO:0000305}. FT SITE 1037 1037 Interaction with DNA. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000244|PubMed:22814378}. FT MOD_RES 426 426 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 440 440 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 453 453 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 467 467 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 1133 1133 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT VARIANT 32 32 K -> R (in dbSNP:rs34477820). FT {ECO:0000269|PubMed:11161804}. FT /FTId=VAR_017453. FT VARIANT 92 92 G -> V (in a colorectal cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036318. FT VARIANT 114 114 V -> I (polymorphism; no effect on FT exonuclease activity; dbSNP:rs2230009). FT {ECO:0000269|PubMed:11161804, FT ECO:0000269|PubMed:16622405, FT ECO:0000269|Ref.4}. FT /FTId=VAR_017454. FT VARIANT 125 125 K -> N (in WRN). FT {ECO:0000269|PubMed:16673358}. FT /FTId=VAR_026588. FT VARIANT 135 135 K -> E (in WRN). FT {ECO:0000269|PubMed:16673358}. FT /FTId=VAR_026589. FT VARIANT 172 172 T -> P (polymorphism; no effect on FT exonuclease activity). FT {ECO:0000269|PubMed:11161804, FT ECO:0000269|PubMed:16622405}. FT /FTId=VAR_017455. FT VARIANT 240 240 N -> K (in dbSNP:rs148229804). FT {ECO:0000269|PubMed:11161804}. FT /FTId=VAR_017456. FT VARIANT 324 324 T -> A (in dbSNP:rs1800390). FT {ECO:0000269|PubMed:10069711}. FT /FTId=VAR_006904. FT VARIANT 329 329 Q -> R (in dbSNP:rs4987237). FT /FTId=VAR_020450. FT VARIANT 343 343 E -> K (in dbSNP:rs11574222). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_018941. FT VARIANT 383 383 L -> F (in dbSNP:rs4987238). FT /FTId=VAR_020451. FT VARIANT 383 383 L -> W. {ECO:0000269|PubMed:11161804}. FT /FTId=VAR_017457. FT VARIANT 387 387 M -> I (in dbSNP:rs1800391). FT {ECO:0000269|PubMed:10206685, FT ECO:0000269|PubMed:11161804, FT ECO:0000269|PubMed:9450180, FT ECO:0000269|Ref.4}. FT /FTId=VAR_006905. FT VARIANT 533 533 N -> S (in dbSNP:rs11574240). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_018942. FT VARIANT 612 612 S -> C (in dbSNP:rs11574250). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_018943. FT VARIANT 708 708 S -> F (in dbSNP:rs11574289). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_018944. FT VARIANT 711 711 R -> W (in dbSNP:rs34560788). FT /FTId=VAR_057124. FT VARIANT 724 724 Q -> L. {ECO:0000269|PubMed:11161804}. FT /FTId=VAR_017458. FT VARIANT 834 834 R -> C (in dbSNP:rs3087425). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014913. FT VARIANT 912 912 I -> S (in dbSNP:rs11574323). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_018945. FT VARIANT 1074 1074 L -> F (in dbSNP:rs1801195). FT {ECO:0000269|PubMed:11161804, FT ECO:0000269|PubMed:16723399, FT ECO:0000269|PubMed:8602509, FT ECO:0000269|PubMed:9450180, FT ECO:0000269|Ref.3}. FT /FTId=VAR_007903. FT VARIANT 1079 1079 S -> L (in dbSNP:rs3087414). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014914. FT VARIANT 1133 1133 S -> A (in dbSNP:rs11574358). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_018946. FT VARIANT 1141 1141 S -> L. {ECO:0000269|PubMed:18987736}. FT /FTId=VAR_054162. FT VARIANT 1269 1269 K -> E. {ECO:0000269|PubMed:11161804}. FT /FTId=VAR_017459. FT VARIANT 1339 1339 V -> I (in dbSNP:rs11574395). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_018947. FT VARIANT 1367 1367 C -> R (polymorphism associated with a FT higher risk of myocardial infarction; FT dbSNP:rs1346044). FT {ECO:0000269|PubMed:10069711, FT ECO:0000269|PubMed:11161804, FT ECO:0000269|PubMed:9021029, FT ECO:0000269|Ref.4}. FT /FTId=VAR_006906. FT MUTAGEN 84 84 E->A: Abolishes exonuclease activity. FT {ECO:0000269|PubMed:11863428, FT ECO:0000269|PubMed:16622405}. FT MUTAGEN 88 88 L->A: No effect on exonuclease activity. FT MUTAGEN 145 145 W->A: Reduces exonuclease activity. FT {ECO:0000269|PubMed:16622405}. FT MUTAGEN 212 212 Y->F: Strongly reduces exonuclease FT activity. {ECO:0000269|PubMed:16622405}. FT MUTAGEN 987 987 R->A: Reduces affinity for DNA about 8- FT fold. Loss of DNA binding; when FT associated with A-993. FT {ECO:0000269|PubMed:20159463}. FT MUTAGEN 989 989 S->A: Reduces affinity for DNA about 4- FT fold. {ECO:0000269|PubMed:20159463}. FT MUTAGEN 993 993 R->A: Reduces affinity for DNA about 20- FT fold. Loss of DNA binding; when FT associated with A-987. FT {ECO:0000269|PubMed:20159463}. FT MUTAGEN 993 993 R->E: Loss of DNA binding. FT {ECO:0000269|PubMed:20159463}. FT MUTAGEN 1037 1037 F->A: Reduces affinity for DNA about 8- FT fold. {ECO:0000269|PubMed:20159463}. FT MUTAGEN 1038 1038 M->A: Reduces affinity for DNA about 4- FT fold. {ECO:0000269|PubMed:20159463}. FT HELIX 39 41 {ECO:0000244|PDB:2FBY}. FT STRAND 51 56 {ECO:0000244|PDB:2FBY}. FT HELIX 59 72 {ECO:0000244|PDB:2FBY}. FT STRAND 78 84 {ECO:0000244|PDB:2FBY}. FT STRAND 99 105 {ECO:0000244|PDB:2FBY}. FT STRAND 108 112 {ECO:0000244|PDB:2FBY}. FT HELIX 114 116 {ECO:0000244|PDB:2FBY}. FT STRAND 117 119 {ECO:0000244|PDB:2FBY}. FT HELIX 122 128 {ECO:0000244|PDB:2FBY}. FT STRAND 133 139 {ECO:0000244|PDB:2FBY}. FT HELIX 140 151 {ECO:0000244|PDB:2FBY}. FT STRAND 157 160 {ECO:0000244|PDB:2FBY}. FT HELIX 161 169 {ECO:0000244|PDB:2FBY}. FT HELIX 177 185 {ECO:0000244|PDB:2FBY}. FT HELIX 193 196 {ECO:0000244|PDB:2FBY}. FT STRAND 202 204 {ECO:0000244|PDB:2FBY}. FT HELIX 207 228 {ECO:0000244|PDB:2FBY}. FT STRAND 955 958 {ECO:0000244|PDB:2AXL}. FT HELIX 960 972 {ECO:0000244|PDB:3AAF}. FT TURN 973 975 {ECO:0000244|PDB:3AAF}. FT HELIX 980 986 {ECO:0000244|PDB:3AAF}. FT HELIX 996 1000 {ECO:0000244|PDB:3AAF}. FT TURN 1002 1009 {ECO:0000244|PDB:3AAF}. FT HELIX 1012 1024 {ECO:0000244|PDB:3AAF}. FT STRAND 1027 1032 {ECO:0000244|PDB:3AAF}. FT TURN 1036 1038 {ECO:0000244|PDB:2AXL}. FT STRAND 1039 1043 {ECO:0000244|PDB:3AAF}. FT HELIX 1045 1054 {ECO:0000244|PDB:3AAF}. FT STRAND 1062 1064 {ECO:0000244|PDB:2AXL}. FT HELIX 1147 1171 {ECO:0000244|PDB:2E1F}. FT HELIX 1175 1178 {ECO:0000244|PDB:2E1F}. FT HELIX 1181 1190 {ECO:0000244|PDB:2E1F}. FT HELIX 1195 1198 {ECO:0000244|PDB:2E1F}. FT STRAND 1201 1203 {ECO:0000244|PDB:2DGZ}. FT HELIX 1206 1211 {ECO:0000244|PDB:2E1F}. FT HELIX 1213 1225 {ECO:0000244|PDB:2E1F}. SQ SEQUENCE 1432 AA; 162461 MW; 63F10D19E90AA461 CRC64; MSEKKLETTA QQRKCPEWMN VQNKRCAVEE RKACVRKSVF EDDLPFLEFT GSIVYSYDAS DCSFLSEDIS MSLSDGDVVG FDMEWPPLYN RGKLGKVALI QLCVSESKCY LFHVSSMSVF PQGLKMLLEN KAVKKAGVGI EGDQWKLLRD FDIKLKNFVE LTDVANKKLK CTETWSLNSL VKHLLGKQLL KDKSIRCSNW SKFPLTEDQK LYAATDAYAG FIIYRNLEIL DDTVQRFAIN KEEEILLSDM NKQLTSISEE VMDLAKHLPH AFSKLENPRR VSILLKDISE NLYSLRRMII GSTNIETELR PSNNLNLLSF EDSTTGGVQQ KQIREHEVLI HVEDETWDPT LDHLAKHDGE DVLGNKVERK EDGFEDGVED NKLKENMERA CLMSLDITEH ELQILEQQSQ EEYLSDIAYK STEHLSPNDN ENDTSYVIES DEDLEMEMLK HLSPNDNEND TSYVIESDED LEMEMLKSLE NLNSGTVEPT HSKCLKMERN LGLPTKEEEE DDENEANEGE EDDDKDFLWP APNEEQVTCL KMYFGHSSFK PVQWKVIHSV LEERRDNVAV MATGYGKSLC FQYPPVYVGK IGLVISPLIS LMEDQVLQLK MSNIPACFLG SAQSENVLTD IKLGKYRIVY VTPEYCSGNM GLLQQLEADI GITLIAVDEA HCISEWGHDF RDSFRKLGSL KTALPMVPIV ALTATASSSI REDIVRCLNL RNPQITCTGF DRPNLYLEVR RKTGNILQDL QPFLVKTSSH WEFEGPTIIY CPSRKMTQQV TGELRKLNLS CGTYHAGMSF STRKDIHHRF VRDEIQCVIA TIAFGMGINK ADIRQVIHYG APKDMESYYQ EIGRAGRDGL QSSCHVLWAP ADINLNRHLL TEIRNEKFRL YKLKMMAKME KYLHSSRCRR QIILSHFEDK QVQKASLGIM GTEKCCDNCR SRLDHCYSMD DSEDTSWDFG PQAFKLLSAV DILGEKFGIG LPILFLRGSN SQRLADQYRR HSLFGTGKDQ TESWWKAFSR QLITEGFLVE VSRYNKFMKI CALTKKGRNW LHKANTESQS LILQANEELC PKKLLLPSSK TVSSGTKEHC YNQVPVELST EKKSNLEKLY SYKPCDKISS GSNISKKSIM VQSPEKAYSS SQPVISAQEQ ETQIVLYGKL VEARQKHANK MDVPPAILAT NKILVDMAKM RPTTVENVKR IDGVSEGKAA MLAPLLEVIK HFCQTNSVQT DLFSSTKPQE EQKTSLVAKN KICTLSQSMA ITYSLFQEKK MPLKSIAESR ILPLMTIGMH LSQAVKAGCP LDLERAGLTP EVQKIIADVI RNPPVNSDMS KISLIRMLVP ENIDTYLIHM AIEILKHGPD SGLQPSCDVN KRRCFPGSEE ICSSSKRSKE EVGINTETSS AERKRRLPVW FAKGSDTSKK LMDKTKRGGL FS //