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Q14191 (WRN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 166. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Werner syndrome ATP-dependent helicase

EC=3.6.4.12
Alternative name(s):
DNA helicase, RecQ-like type 3
Short name=RecQ3
Exonuclease WRN
EC=3.1.-.-
RecQ protein-like 2
Gene names
Name:WRN
Synonyms:RECQ3, RECQL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1432 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A By similarity. Plays a role in double-strand break repair after gamma-irradiation. Ref.8 Ref.12 Ref.14 Ref.17 Ref.18 Ref.21

Catalytic activity

ATP + H2O = ADP + phosphate. Ref.25

Cofactor

Binds 2 magnesium ions per subunit. Has high activity with manganese and zinc ions (in vitro). Ref.25

Subunit structure

Monomer, and homooligomer. May exist as homodimer, homotrimer, homotetramer and/or homohexamer. Homotetramer, or homohexamer, when bound to DNA. Interacts via its N-terminal domain with WRNIP1 By similarity. Interacts with EXO1, PCNA and SUPV3L1. Interacts with PML (isoform PML-4) Ref.8 Ref.10 Ref.11 Ref.14 Ref.21 Ref.29

Subcellular location

Nucleusnucleolus. Nucleus. Nucleusnucleoplasm. Note: Gamma-irradiation leads to its translocation from nucleoli to nucleoplasm and PML regulates the irradiation-induced WRN relocation. Ref.6 Ref.12 Ref.17 Ref.21

Post-translational modification

Phosphorylated by PRKDC. Ref.9

Involvement in disease

Werner syndrome (WRN) [MIM:277700]: A rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.36

Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Note: The disease may be caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the helicase family. RecQ subfamily.

Contains 1 3'-5' exonuclease domain.

Contains 1 helicase ATP-binding domain.

Contains 1 helicase C-terminal domain.

Contains 1 HRDC domain.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainRepeat
   LigandATP-binding
DNA-binding
Magnesium
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionExonuclease
Helicase
Hydrolase
Nuclease
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from direct assay PubMed 10373438PubMed 10871376. Source: GOC

DNA duplex unwinding

Inferred from direct assay PubMed 11433031PubMed 12944467PubMed 17715146PubMed 9288107. Source: GOC

DNA metabolic process

Inferred from direct assay Ref.25. Source: UniProtKB

DNA recombination

Inferred from electronic annotation. Source: InterPro

DNA replication

Inferred from mutant phenotype PubMed 12882351. Source: UniProtKB

DNA synthesis involved in DNA repair

Inferred from direct assay Ref.12. Source: UniProtKB

aging

Non-traceable author statement PubMed 9288107. Source: UniProtKB

base-excision repair

Inferred from direct assay PubMed 17611195. Source: UniProtKB

cell aging

Inferred from mutant phenotype PubMed 18212065. Source: UniProtKB

cellular response to DNA damage stimulus

Inferred from direct assay PubMed 18203716. Source: UniProtKB

cellular response to gamma radiation

Inferred from direct assay Ref.21. Source: UniProtKB

cellular response to starvation

Inferred from direct assay PubMed 11420665. Source: MGI

double-strand break repair

Inferred from mutant phenotype Ref.21. Source: UniProtKB

multicellular organismal aging

Inferred from mutant phenotype Ref.36. Source: UniProtKB

nucleic acid phosphodiester bond hydrolysis

Inferred from direct assay PubMed 10783163PubMed 10871373PubMed 12181313PubMed 12944467Ref.25. Source: GOC

nucleolus to nucleoplasm transport

Inferred from direct assay PubMed 11420665. Source: MGI

positive regulation of hydrolase activity

Inferred from direct assay PubMed 17611195. Source: UniProtKB

regulation of apoptotic process

Inferred from genetic interaction PubMed 9681877. Source: MGI

regulation of growth rate

Inferred from electronic annotation. Source: Ensembl

replication fork processing

Inferred from direct assay PubMed 17115688. Source: UniProtKB

replicative cell aging

Inferred from electronic annotation. Source: Ensembl

response to UV-C

Inferred from direct assay Ref.12. Source: UniProtKB

response to oxidative stress

Inferred from direct assay PubMed 17611195. Source: UniProtKB

telomere maintenance

Inferred from mutant phenotype PubMed 18212065. Source: UniProtKB

   Cellular_componentcentrosome

Inferred from direct assay PubMed 17498979. Source: UniProtKB

nucleolus

Inferred from direct assay PubMed 12181313Ref.21Ref.6. Source: UniProtKB

nucleoplasm

Inferred from direct assay Ref.21. Source: UniProtKB

   Molecular_function3'-5' DNA helicase activity

Inferred from direct assay PubMed 17715146. Source: UniProtKB

3'-5' exonuclease activity

Inferred from direct assay PubMed 10783163PubMed 12181313Ref.25. Source: UniProtKB

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATP-dependent 3'-5' DNA helicase activity

Inferred from electronic annotation. Source: InterPro

ATP-dependent DNA helicase activity

Inferred from direct assay PubMed 9288107. Source: UniProtKB

ATPase activity

Inferred from direct assay PubMed 10373438PubMed 10871376. Source: UniProtKB

DNA binding

Inferred from direct assay PubMed 9288107. Source: UniProtKB

DNA helicase activity

Inferred from mutant phenotype PubMed 10871376. Source: UniProtKB

G-quadruplex DNA binding

Inferred from direct assay PubMed 11433031. Source: UniProtKB

Y-form DNA binding

Inferred from direct assay PubMed 17715146. Source: UniProtKB

bubble DNA binding

Inferred from direct assay PubMed 11433031. Source: UniProtKB

exonuclease activity

Inferred from direct assay PubMed 12944467. Source: MGI

four-way junction helicase activity

Inferred from direct assay PubMed 11433031. Source: UniProtKB

helicase activity

Inferred from direct assay PubMed 12181313. Source: UniProtKB

magnesium ion binding

Inferred from direct assay Ref.25. Source: UniProtKB

manganese ion binding

Inferred from direct assay Ref.25. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10783163PubMed 12181313PubMed 17498979PubMed 17611195PubMed 17715146Ref.11PubMed 18203716Ref.21. Source: UniProtKB

protein complex binding

Inferred from direct assay PubMed 10783163. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 10783163. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.23
Chain2 – 14321431Werner syndrome ATP-dependent helicase
PRO_0000205045

Regions

Domain60 – 2281693'-5' exonuclease
Repeat424 – 450271
Repeat451 – 477272
Domain558 – 724167Helicase ATP-binding
Domain749 – 899151Helicase C-terminal
Domain1150 – 122980HRDC
Nucleotide binding571 – 5788ATP By similarity
Region2 – 277276Interaction with WRNIP1 By similarity
Region424 – 477542 X 27 AA tandem repeats of H-L-S-P-N-D-N-E-N-D-T-S-Y-V-I-E-S-D-E-D-L-E-M-E-M-L-K
Region987 – 9937Interaction with DNA
Motif668 – 6714DEAH box
Compositional bias507 – 5104Poly-Glu

Sites

Metal binding821Magnesium 1; catalytic
Metal binding821Magnesium 2; catalytic
Metal binding841Magnesium 1; catalytic
Metal binding2161Magnesium 1; catalytic
Site1451Interaction with DNA Probable
Site10371Interaction with DNA

Amino acid modifications

Modified residue21N-acetylserine Ref.23
Modified residue4261Phosphoserine Ref.19
Modified residue4401Phosphoserine Ref.15 Ref.19
Modified residue4531Phosphoserine Ref.19
Modified residue4671Phosphoserine Ref.15 Ref.19
Modified residue11331Phosphoserine Ref.22

Natural variations

Natural variant321K → R. Ref.35
Corresponds to variant rs34477820 [ dbSNP | Ensembl ].
VAR_017453
Natural variant921G → V in a colorectal cancer sample; somatic mutation. Ref.37
VAR_036318
Natural variant1141V → I No effect on exonuclease activity. Ref.4 Ref.25 Ref.35
Corresponds to variant rs2230009 [ dbSNP | Ensembl ].
VAR_017454
Natural variant1251K → N in WRN. Ref.36
VAR_026588
Natural variant1351K → E in WRN. Ref.36
VAR_026589
Natural variant1721T → P No effect on exonuclease activity. Ref.25 Ref.35
VAR_017455
Natural variant2401N → K. Ref.35
Corresponds to variant rs148229804 [ dbSNP | Ensembl ].
VAR_017456
Natural variant3241T → A. Ref.34
Corresponds to variant rs1800390 [ dbSNP | Ensembl ].
VAR_006904
Natural variant3291Q → R.
Corresponds to variant rs4987237 [ dbSNP | Ensembl ].
VAR_020450
Natural variant3431E → K. Ref.4
Corresponds to variant rs11574222 [ dbSNP | Ensembl ].
VAR_018941
Natural variant3831L → F.
Corresponds to variant rs4987238 [ dbSNP | Ensembl ].
VAR_020451
Natural variant3831L → W. Ref.35
VAR_017457
Natural variant3871M → I. Ref.4 Ref.32 Ref.33 Ref.35
Corresponds to variant rs1800391 [ dbSNP | Ensembl ].
VAR_006905
Natural variant5331N → S. Ref.4
Corresponds to variant rs11574240 [ dbSNP | Ensembl ].
VAR_018942
Natural variant6121S → C. Ref.4
Corresponds to variant rs11574250 [ dbSNP | Ensembl ].
VAR_018943
Natural variant7081S → F. Ref.4
Corresponds to variant rs11574289 [ dbSNP | Ensembl ].
VAR_018944
Natural variant7111R → W.
Corresponds to variant rs34560788 [ dbSNP | Ensembl ].
VAR_057124
Natural variant7241Q → L. Ref.35
VAR_017458
Natural variant8341R → C. Ref.4
Corresponds to variant rs3087425 [ dbSNP | Ensembl ].
VAR_014913
Natural variant9121I → S. Ref.4
Corresponds to variant rs11574323 [ dbSNP | Ensembl ].
VAR_018945
Natural variant10741L → F. Ref.1 Ref.2 Ref.3 Ref.32 Ref.35
Corresponds to variant rs1801195 [ dbSNP | Ensembl ].
VAR_007903
Natural variant10791S → L. Ref.4
Corresponds to variant rs3087414 [ dbSNP | Ensembl ].
VAR_014914
Natural variant11331S → A. Ref.4
Corresponds to variant rs11574358 [ dbSNP | Ensembl ].
VAR_018946
Natural variant11411S → L. Ref.38
VAR_054162
Natural variant12691K → E. Ref.35
VAR_017459
Natural variant13391V → I. Ref.4
Corresponds to variant rs11574395 [ dbSNP | Ensembl ].
VAR_018947
Natural variant13671C → R Polymorphism associated with a higher risk of myocardial infarction. Ref.4 Ref.30 Ref.34 Ref.35
Corresponds to variant rs1346044 [ dbSNP | Ensembl ].
VAR_006906

Experimental info

Mutagenesis841E → A: Abolishes exonuclease activity. Ref.8 Ref.25
Mutagenesis881L → A: No effect on exonuclease activity.
Mutagenesis1451W → A: Reduces exonuclease activity. Ref.25
Mutagenesis2121Y → F: Strongly reduces exonuclease activity. Ref.25
Mutagenesis9871R → A: Reduces affinity for DNA about 8-fold. Loss of DNA binding; when associated with A-993. Ref.29
Mutagenesis9891S → A: Reduces affinity for DNA about 4-fold. Ref.29
Mutagenesis9931R → A: Reduces affinity for DNA about 20-fold. Loss of DNA binding; when associated with A-987. Ref.29
Mutagenesis9931R → E: Loss of DNA binding. Ref.29
Mutagenesis10371F → A: Reduces affinity for DNA about 8-fold. Ref.29
Mutagenesis10381M → A: Reduces affinity for DNA about 4-fold. Ref.29

Secondary structure

.................................................................... 1432
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q14191 [UniParc].

Last modified February 8, 2011. Version 2.
Checksum: 63F10D19E90AA461

FASTA1,432162,461
        10         20         30         40         50         60 
MSEKKLETTA QQRKCPEWMN VQNKRCAVEE RKACVRKSVF EDDLPFLEFT GSIVYSYDAS 

        70         80         90        100        110        120 
DCSFLSEDIS MSLSDGDVVG FDMEWPPLYN RGKLGKVALI QLCVSESKCY LFHVSSMSVF 

       130        140        150        160        170        180 
PQGLKMLLEN KAVKKAGVGI EGDQWKLLRD FDIKLKNFVE LTDVANKKLK CTETWSLNSL 

       190        200        210        220        230        240 
VKHLLGKQLL KDKSIRCSNW SKFPLTEDQK LYAATDAYAG FIIYRNLEIL DDTVQRFAIN 

       250        260        270        280        290        300 
KEEEILLSDM NKQLTSISEE VMDLAKHLPH AFSKLENPRR VSILLKDISE NLYSLRRMII 

       310        320        330        340        350        360 
GSTNIETELR PSNNLNLLSF EDSTTGGVQQ KQIREHEVLI HVEDETWDPT LDHLAKHDGE 

       370        380        390        400        410        420 
DVLGNKVERK EDGFEDGVED NKLKENMERA CLMSLDITEH ELQILEQQSQ EEYLSDIAYK 

       430        440        450        460        470        480 
STEHLSPNDN ENDTSYVIES DEDLEMEMLK HLSPNDNEND TSYVIESDED LEMEMLKSLE 

       490        500        510        520        530        540 
NLNSGTVEPT HSKCLKMERN LGLPTKEEEE DDENEANEGE EDDDKDFLWP APNEEQVTCL 

       550        560        570        580        590        600 
KMYFGHSSFK PVQWKVIHSV LEERRDNVAV MATGYGKSLC FQYPPVYVGK IGLVISPLIS 

       610        620        630        640        650        660 
LMEDQVLQLK MSNIPACFLG SAQSENVLTD IKLGKYRIVY VTPEYCSGNM GLLQQLEADI 

       670        680        690        700        710        720 
GITLIAVDEA HCISEWGHDF RDSFRKLGSL KTALPMVPIV ALTATASSSI REDIVRCLNL 

       730        740        750        760        770        780 
RNPQITCTGF DRPNLYLEVR RKTGNILQDL QPFLVKTSSH WEFEGPTIIY CPSRKMTQQV 

       790        800        810        820        830        840 
TGELRKLNLS CGTYHAGMSF STRKDIHHRF VRDEIQCVIA TIAFGMGINK ADIRQVIHYG 

       850        860        870        880        890        900 
APKDMESYYQ EIGRAGRDGL QSSCHVLWAP ADINLNRHLL TEIRNEKFRL YKLKMMAKME 

       910        920        930        940        950        960 
KYLHSSRCRR QIILSHFEDK QVQKASLGIM GTEKCCDNCR SRLDHCYSMD DSEDTSWDFG 

       970        980        990       1000       1010       1020 
PQAFKLLSAV DILGEKFGIG LPILFLRGSN SQRLADQYRR HSLFGTGKDQ TESWWKAFSR 

      1030       1040       1050       1060       1070       1080 
QLITEGFLVE VSRYNKFMKI CALTKKGRNW LHKANTESQS LILQANEELC PKKLLLPSSK 

      1090       1100       1110       1120       1130       1140 
TVSSGTKEHC YNQVPVELST EKKSNLEKLY SYKPCDKISS GSNISKKSIM VQSPEKAYSS 

      1150       1160       1170       1180       1190       1200 
SQPVISAQEQ ETQIVLYGKL VEARQKHANK MDVPPAILAT NKILVDMAKM RPTTVENVKR 

      1210       1220       1230       1240       1250       1260 
IDGVSEGKAA MLAPLLEVIK HFCQTNSVQT DLFSSTKPQE EQKTSLVAKN KICTLSQSMA 

      1270       1280       1290       1300       1310       1320 
ITYSLFQEKK MPLKSIAESR ILPLMTIGMH LSQAVKAGCP LDLERAGLTP EVQKIIADVI 

      1330       1340       1350       1360       1370       1380 
RNPPVNSDMS KISLIRMLVP ENIDTYLIHM AIEILKHGPD SGLQPSCDVN KRRCFPGSEE 

      1390       1400       1410       1420       1430 
ICSSSKRSKE EVGINTETSS AERKRRLPVW FAKGSDTSKK LMDKTKRGGL FS 

« Hide

References

« Hide 'large scale' references
[1]"Positional cloning of the Werner's syndrome gene."
Yu C.-E., Oshima J., Fu Y.-H., Wijsman E.M., Hisama F., Alisch R., Matthews S., Nakura J., Miki T., Ouais S., Martin G.M., Mulligan J., Schellenberg G.D.
Science 272:258-262(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PHE-1074.
[2]"Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer."
Agrelo R., Cheng W.H., Setien F., Ropero S., Espada J., Fraga M.F., Herranz M., Paz M.F., Sanchez-Cespedes M., Artiga M.J., Guerrero D., Castells A., von Kobbe C., Bohr V.A., Esteller M.
Proc. Natl. Acad. Sci. U.S.A. 103:8822-8827(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PHE-1074.
[3]"Genomic structure of the human Werner's gene and cloning of the mouse homolog."
Paeper B.W., Gayle M., Brady W., Swartz A., Gillett L.A., Alisch R.S., Mulligan J., Galas D., Fu Y.-H.
Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PHE-1074.
[4]NIEHS SNPs program
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-114; LYS-343; ILE-387; SER-533; CYS-612; PHE-708; CYS-834; SER-912; LEU-1079; ALA-1133; ILE-1339 AND ARG-1367.
[5]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Nucleolar localization of the Werner syndrome protein in human cells."
Marciniak R.A., Lombard D.B., Johnson F.B., Guarente L.
Proc. Natl. Acad. Sci. U.S.A. 95:6887-6892(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"Evolution of the RECQ family of helicases: a Drosophila homolog, Dmblm, is similar to the human Bloom syndrome gene."
Kusano K., Berres M.E., Engels W.R.
Genetics 151:1027-1039(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REPEATS.
[8]"A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3'- 5' exonuclease and 5'-protruding strand endonuclease activities."
Xue Y., Ratcliff G.C., Wang H., Davis-Searles P.R., Gray M.D., Erie D.A., Redinbo M.R.
Biochemistry 41:2901-2912(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLU-84, FUNCTION AS AN EXONUCLEASE, DNA-BINDING, INTERACTION WITH PCNA, SUBUNIT.
[9]"Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation."
Karmakar P., Piotrowski J., Brosh R.M. Jr., Sommers J.A., Miller S.P., Cheng W.H., Snowden C.M., Ramsden D.A., Bohr V.A.
J. Biol. Chem. 277:18291-18302(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[10]"The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein."
Sharma S., Sommers J.A., Driscoll H.C., Uzdilla L.A., Wilson T.M., Brosh R.M. Jr.
J. Biol. Chem. 278:23487-23496(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EXO1.
[11]"Interaction of human SUV3 RNA/DNA helicase with BLM helicase; loss of the SUV3 gene results in mouse embryonic lethality."
Pereira M., Mason P., Szczesny R.J., Maddukuri L., Dziwura S., Jedrzejczak R., Paul E., Wojcik A., Dybczynska L., Tudek B., Bartnik E., Klysik J., Bohr V.A., Stepien P.P.
Mech. Ageing Dev. 128:609-617(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SUPV3L1.
[12]"Werner syndrome protein interacts functionally with translesion DNA polymerases."
Kamath-Loeb A.S., Lan L., Nakajima S., Yasui A., Loeb L.A.
Proc. Natl. Acad. Sci. U.S.A. 104:10394-10399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[13]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[14]"The Werner syndrome protein binds replication fork and Holliday junction DNAs as an oligomer."
Compton S.A., Tolun G., Kamath-Loeb A.S., Loeb L.A., Griffith J.D.
J. Biol. Chem. 283:24478-24483(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, DNA-BINDING.
[15]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-440 AND SER-467, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts."
Zecevic A., Menard H., Gurel V., Hagan E., DeCaro R., Zhitkovich A.
Cell Cycle 8:2769-2778(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[18]"The Werner syndrome helicase/exonuclease processes mobile D-loops through branch migration and degradation."
Opresko P.L., Sowd G., Wang H.
PLoS ONE 4:E4825-E4825(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-426; SER-440; SER-453 AND SER-467, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[20]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in gamma-irradiation-induced DNA damage responses."
Liu J., Song Y., Qian J., Liu B., Dong Y., Tian B., Sun Z.
Biochemistry (Mosc.) 76:550-554(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PML.
[22]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1133, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[24]"Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein."
Hu J.S., Feng H., Zeng W., Lin G.X., Xi X.G.
Proc. Natl. Acad. Sci. U.S.A. 102:18379-18384(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 949-1092.
[25]"WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing."
Perry J.J., Yannone S.M., Holden L.G., Hitomi C., Asaithamby A., Han S., Cooper P.K., Chen D.J., Tainer J.A.
Nat. Struct. Mol. Biol. 13:414-422(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 38-236 IN COMPLEXES WITH MAGNESIUM; MANGANESE; EUROPIUM AND GMP, PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF GLU-84; TRP-145 AND TYR-212, CHARACTERIZATION OF VARIANTS ILE-114 AND PRO-172.
[26]"WRN mutations in Werner syndrome."
Moser M.J., Oshima J., Monnat R.J. Jr.
Hum. Mutat. 13:271-279(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[27]"Solution structure of the helicase and RNase D C-terminal domain in Werner syndrome ATP-dependent helicase."
RIKEN structural genomics initiative (RSGI)
Submitted (SEP-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 1140-1239.
[28]"Crystal structure of the HRDC domain of human Werner syndrome protein, WRN."
Kitano K., Yoshihara N., Hakoshima T.
J. Biol. Chem. 282:2717-2728(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1142-1242, PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, CIRCULAR DICHROISM.
[29]"Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicase WRN."
Kitano K., Kim S.Y., Hakoshima T.
Structure 18:177-187(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 949-1079 IN COMPLEX WITH DOUBLE-STRANDED DNA, INTERACTION WITH DNA, MUTAGENESIS OF ARG-987; SER-989; ARG-993; PHE-1037 AND MET-1038.
[30]"Association of a polymorphic variant of the Werner helicase gene with myocardial infarction in a Japanese population."
Ye L., Miki T., Nakura J., Oshima J., Kamino K., Rakugi H., Ikegami H., Higaki J., Edland S.D., Martin G.M., Ogihara T.
Am. J. Med. Genet. 68:494-498(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARG-1367.
[31]Erratum
Ye L., Miki T., Nakura J., Oshima J., Kamino K., Rakugi H., Ikegami H., Higaki J., Edland S.D., Martin G.M., Ogihara T.
Am. J. Med. Genet. 70:103-103(1997)
[32]"Werner syndrome: characterization of mutations in the WRN gene in an affected family."
Meisslitzer C., Ruppitsch W., Weirich-Schwaiger H., Weirich H.G., Jabkowsky J., Klein G., Schweiger M., Hirsch-Kauffmann M.
Eur. J. Hum. Genet. 5:364-370(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ILE-387 AND PHE-1074.
[33]"The 1396del A mutation and a missense mutation or a rare polymorphism of the WRN gene detected in a French Werner family with a severe phenotype and a case of an unusual vulvar cancer."
Vidal V., Bay J.-O., Champomier F., Grancho M., Beauville L., Glowaczower C., Lemery D., Ferrara M., Bignon Y.-J.
Hum. Mutat. 11:413-414(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ILE-387.
[34]"Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cys/Arg, and its stability in a population of Finnish centenarians."
Castro E., Ogburn C.E., Hunt K.E., Tilvis R., Louhija J., Penttinen R., Erkkola R., Panduro A., Riestra R., Piussan C., Deeb S.S., Wang L., Edland S.D., Martin G.M., Oshima J.
Am. J. Med. Genet. 82:399-403(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-324 AND ARG-1367.
[35]"The Werner syndrome gene and global sequence variation."
Passarino G., Shen P., Van Kirk J.B., Lin A.A., De Benedictis G., Cavalli-Sforza L.L., Oefner P.J., Underhill P.A.
Genomics 71:118-122(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARG-32; ILE-114; PRO-172; LYS-240; TRP-383; ILE-387; LEU-724; PHE-1074; GLU-1269 AND ARG-1367.
[36]"The spectrum of WRN mutations in Werner syndrome patients."
Huang S., Lee L., Hanson N.B., Lenaerts C., Hoehn H., Poot M., Rubin C.D., Chen D.-F., Yang C.-C., Juch H., Dorn T., Spiegel R., Oral E.A., Abid M., Battisti C., Lucci-Cordisco E., Neri G., Steed E.H. expand/collapse author list , Kidd A., Isley W., Showalter D., Vittone J.L., Konstantinow A., Ring J., Meyer P., Wenger S.L., Herbay A.V., Wollina U., Schuelke M., Huizenga C.R., Leistritz D.F., Martin G.M., Mian I.S., Oshima J.
Hum. Mutat. 27:558-567(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS WRN ASN-125 AND GLU-135.
[37]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-92.
[38]"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome."
Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. expand/collapse author list , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K.
Nature 456:66-72(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-1141.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L76937 Genomic DNA. Translation: AAC41981.1.
AY818673 mRNA. Translation: AAX21098.1.
AF091214 mRNA. Translation: AAC63361.1.
AF181897, AF181896 Genomic DNA. Translation: AAF06162.1.
AY442327 Genomic DNA. Translation: AAR05448.1.
AC084736 Genomic DNA. No translation available.
CCDSCCDS6082.1.
RefSeqNP_000544.2. NM_000553.4.
UniGeneHs.632050.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2AXLNMR-A949-1092[»]
2DGZNMR-A1140-1239[»]
2E1EX-ray2.30A1142-1242[»]
2E1FX-ray2.00A1142-1242[»]
2FBTX-ray2.05A38-236[»]
2FBVX-ray2.40A38-236[»]
2FBXX-ray2.20A38-236[»]
2FBYX-ray2.00A38-236[»]
2FC0X-ray2.00A38-236[»]
3AAFX-ray1.90A/B949-1079[»]
DisProtDP00443.
ProteinModelPortalQ14191.
SMRQ14191. Positions 38-231, 532-1235.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113323. 42 interactions.
DIPDIP-31380N.
IntActQ14191. 20 interactions.
MINTMINT-95856.
STRING9606.ENSP00000298139.

Chemistry

ChEMBLCHEMBL2146312.

PTM databases

PhosphoSiteQ14191.

Polymorphism databases

DMDM322510082.

Proteomic databases

MaxQBQ14191.
PaxDbQ14191.
PRIDEQ14191.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000298139; ENSP00000298139; ENSG00000165392.
GeneID7486.
KEGGhsa:7486.
UCSCuc003xio.4. human.

Organism-specific databases

CTD7486.
GeneCardsGC08P030948.
GeneReviewsWRN.
H-InvDBHIX0007441.
HGNCHGNC:12791. WRN.
HPAHPA028661.
MIM114500. phenotype.
277700. phenotype.
604611. gene.
neXtProtNX_Q14191.
Orphanet902. Werner syndrome.
PharmGKBPA367.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0514.
HOGENOMHOG000146447.
HOVERGENHBG000325.
InParanoidQ14191.
KOK10900.
OMAGIEGDQW.
OrthoDBEOG7J70F2.
PhylomeDBQ14191.
TreeFamTF312852.

Gene expression databases

BgeeQ14191.
CleanExHS_WRN.
GenevestigatorQ14191.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
1.10.150.80. 1 hit.
3.30.420.10. 1 hit.
3.40.50.300. 2 hits.
InterProIPR002562. 3'-5'_exonuclease_dom.
IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR004589. DNA_helicase_ATP-dep_RecQ.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR029491. Helicase_HTH.
IPR010997. HRDC-like.
IPR002121. HRDC_dom.
IPR027417. P-loop_NTPase.
IPR012337. RNaseH-like_dom.
IPR018982. RQC_domain.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00270. DEAD. 1 hit.
PF01612. DNA_pol_A_exo1. 1 hit.
PF00271. Helicase_C. 1 hit.
PF00570. HRDC. 1 hit.
PF14493. HTH_40. 1 hit.
PF09382. RQC. 1 hit.
[Graphical view]
SMARTSM00474. 35EXOc. 1 hit.
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SM00341. HRDC. 1 hit.
SM00956. RQC. 1 hit.
[Graphical view]
SUPFAMSSF47819. SSF47819. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53098. SSF53098. 1 hit.
TIGRFAMsTIGR00614. recQ_fam. 1 hit.
PROSITEPS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS50967. HRDC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ14191.
GeneWikiWerner_syndrome_ATP-dependent_helicase.
GenomeRNAi7486.
NextBio29326.
PROQ14191.
SOURCESearch...

Entry information

Entry nameWRN_HUMAN
AccessionPrimary (citable) accession number: Q14191
Secondary accession number(s): A1KYY9
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: February 8, 2011
Last modified: July 9, 2014
This is version 166 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM