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O09053 (WRN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Werner syndrome ATP-dependent helicase homolog

EC=3.6.4.12
Alternative name(s):
Exonuclease WRN
EC=3.1.-.-
Gene names
Name:Wrn
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1401 AA.
Sequence statusComplete.
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 By similarity. Ref.3 Ref.8

Catalytic activity

ATP + H2O = ADP + phosphate.

Cofactor

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

Enzyme regulation

Zinc ions stimulate the exonuclease activity. Ref.8

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. Interacts with PCNA; EXO1 and SUPV3L1 By similarity. Interacts with PML By similarity. Ref.7 Ref.8

Subcellular location

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

Tissue specificity

Expressed ubiquitously in most organs at a low level, highly expressed in testis, ovary and spleen. Ref.1 Ref.3

Post-translational modification

Phosphorylated by PRKDC.

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
   LigandATP-binding
DNA-binding
Magnesium
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionExonuclease
Helicase
Hydrolase
Nuclease
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processDNA metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

DNA recombination

Inferred from electronic annotation. Source: InterPro

DNA replication

Inferred from mutant phenotype PubMed 9789047. Source: MGI

DNA synthesis involved in DNA repair

Inferred from electronic annotation. Source: Ensembl

base-excision repair

Inferred from electronic annotation. Source: Ensembl

cellular response to gamma radiation

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to starvation

Inferred from sequence orthology PubMed 11420665. Source: MGI

double-strand break repair

Inferred from sequence or structural similarity. Source: UniProtKB

multicellular organismal aging

Inferred from genetic interaction PubMed 15235603. Source: MGI

nucleic acid phosphodiester bond hydrolysis

Inferred from direct assay PubMed 10871373. Source: GOC

nucleolus to nucleoplasm transport

Inferred from sequence orthology PubMed 11420665. Source: MGI

positive regulation of hydrolase activity

Inferred from electronic annotation. Source: Ensembl

regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

regulation of growth rate

Inferred from mutant phenotype PubMed 12707040. Source: MGI

replication fork processing

Inferred from electronic annotation. Source: Ensembl

replicative cell aging

Inferred from mutant phenotype Ref.3. Source: MGI

response to UV-C

Inferred from electronic annotation. Source: Ensembl

response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

telomere maintenance

Inferred from mutant phenotype PubMed 12707040. Source: MGI

   Cellular_componentMutLalpha complex

Inferred from electronic annotation. Source: Ensembl

centrosome

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from sequence orthology PubMed 11420665. Source: MGI

nucleoplasm

Inferred from direct assay PubMed 11420665. Source: MGI

nucleus

Inferred from direct assay PubMed 9789047. Source: MGI

   Molecular_function3'-5' exonuclease activity

Inferred from sequence or structural similarity. Source: UniProtKB

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATP-dependent 3'-5' DNA helicase activity

Inferred from electronic annotation. Source: InterPro

G-quadruplex DNA binding

Inferred from electronic annotation. Source: Ensembl

Y-form DNA binding

Inferred from electronic annotation. Source: Ensembl

bubble DNA binding

Inferred from electronic annotation. Source: Ensembl

four-way junction helicase activity

Inferred from electronic annotation. Source: Ensembl

magnesium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

manganese ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.7. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14011401Werner syndrome ATP-dependent helicase homolog
PRO_0000205046

Regions

Domain51 – 2231733'-5' exonuclease
Domain522 – 688167Helicase ATP-binding
Domain713 – 866154Helicase C-terminal
Domain1115 – 119480HRDC
Nucleotide binding535 – 5428ATP By similarity
Region1 – 271271Interaction with WRNIP1
Region952 – 9587Interaction with DNA By similarity
Motif632 – 6354DEAH box
Compositional bias1387 – 13904Poly-Ser

Sites

Metal binding761Magnesium 1; catalytic
Metal binding761Magnesium 2; catalytic
Metal binding781Magnesium 1; catalytic
Metal binding2101Magnesium 1; catalytic
Site1391Interaction with DNA By similarity
Site10021Interaction with DNA By similarity

Amino acid modifications

Modified residue4191Phosphoserine By similarity
Modified residue4331Phosphoserine By similarity
Modified residue10981Phosphoserine By similarity

Experimental info

Mutagenesis1851K → A: Loss of exonuclease activity. Ref.8
Mutagenesis1901R → A: Strongly reduced exonuclease activity. Ref.8
Mutagenesis2061Y → F: Loss of exonuclease activity. Ref.8
Sequence conflict1011S → N in BAA20269. Ref.1
Sequence conflict1011S → N in BAA20270. Ref.1
Sequence conflict1011S → N in AAC72359. Ref.2
Sequence conflict1011S → N in AAF64490. Ref.3
Sequence conflict2281A → V in BAA20269. Ref.1
Sequence conflict2281A → V in BAA20270. Ref.1
Sequence conflict2281A → V in AAC72359. Ref.2
Sequence conflict2281A → V in AAF64490. Ref.3
Sequence conflict2501S → L in BAA20269. Ref.1
Sequence conflict2501S → L in BAA20270. Ref.1
Sequence conflict2501S → L in AAC72359. Ref.2
Sequence conflict2501S → L in AAF64490. Ref.3
Sequence conflict4521V → M in BAA20269. Ref.1
Sequence conflict4521V → M in BAA20270. Ref.1
Sequence conflict4521V → M in AAC72359. Ref.2
Sequence conflict4521V → M in AAF64490. Ref.3
Sequence conflict4591T → K in BAA20269. Ref.1
Sequence conflict4591T → K in BAA20270. Ref.1
Sequence conflict4591T → K in AAC72359. Ref.2
Sequence conflict4591T → K in AAF64490. Ref.3
Sequence conflict4681R → C in BAA20269. Ref.1
Sequence conflict4681R → C in BAA20270. Ref.1
Sequence conflict4681R → C in AAC72359. Ref.2
Sequence conflict4681R → C in AAF64490. Ref.3
Sequence conflict6191Q → K in BAA20269. Ref.1
Sequence conflict6191Q → K in BAA20270. Ref.1
Sequence conflict6191Q → K in AAC72359. Ref.2
Sequence conflict6191Q → K in AAF64490. Ref.3
Sequence conflict8001K → Q in BAA20270. Ref.1
Sequence conflict8001K → Q in BAA20269. Ref.1
Sequence conflict8441L → H in AAC72359. Ref.2
Sequence conflict955 – 98834NSQRL…SHHLI → VSVSVIAPGTVSDSAFHCVA MALAFFRWLTSNPC in AAC72359. Ref.2
Sequence conflict10211S → L in BAA20269. Ref.1
Sequence conflict10211S → L in BAA20270. Ref.1
Sequence conflict10211S → L in AAF64490. Ref.3
Sequence conflict11451T → A in BAA20270. Ref.1
Sequence conflict11451T → A in BAA20269. Ref.1
Sequence conflict11811L → V in BAA20270. Ref.1
Sequence conflict11811L → V in BAA20269. Ref.1
Sequence conflict11821E → G in BAA20269. Ref.1
Sequence conflict11821E → G in BAA20270. Ref.1
Sequence conflict11821E → G in AAF64490. Ref.3
Sequence conflict12521A → V in BAA20269. Ref.1
Sequence conflict12521A → V in BAA20270. Ref.1
Sequence conflict12521A → V in AAF64490. Ref.3
Sequence conflict13081L → I in BAA20269. Ref.1
Sequence conflict13081L → I in BAA20270. Ref.1
Sequence conflict13081L → I in AAF64490. Ref.3
Sequence conflict13561A → V in BAA20269. Ref.1
Sequence conflict13561A → V in BAA20270. Ref.1
Sequence conflict13561A → V in AAF64490. Ref.3

Secondary structure

............................. 1401
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O09053 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 66DF2252B17C24C3

FASTA1,401157,204
        10         20         30         40         50         60 
METTSLQRKF PEWMSMQSQR CATEEKACVQ KSVLEDNLPF LEFPGSIVYS YEASDCSFLS 

        70         80         90        100        110        120 
EDISMRLSDG DVVGFDMEWP PIYKPGKRSR VAVIQLCVSE SKCYLFHISS MSVFPQGLKM 

       130        140        150        160        170        180 
LLENKSIKKA GVGIEGDQWK LLRDFDVKLE SFVELTDVAN EKLKCAETWS LNGLVKHVLG 

       190        200        210        220        230        240 
KQLLKDKSIR CSNWSNFPLT EDQKLYAATD AYAGLIIYQK LGNLGDTAQV FALNKAEENL 

       250        260        270        280        290        300 
PLEMKKQLNS ISEEMRDLAN RFPVTCRNLE TLQRVPVILK SISENLCSLR KVICGPTNTE 

       310        320        330        340        350        360 
TRLKPGSSFN LLSSEDSAAA GEKEKQIGKH STFAKIKEEP WDPELDSLVK QEEVDVFRNQ 

       370        380        390        400        410        420 
VKQEKGESEN EIEDNLLRED MERTCVIPSI SENELQDLEQ QAKEEKYNDV SHQLSEHLSP 

       430        440        450        460        470        480 
NDDENDSSYI IESDEDLEME MLKSLENLNS DVVEPTHSTW LEMGTNGRLP PEEEDGHGNE 

       490        500        510        520        530        540 
AIKEEQEEED HLLPEPNAKQ INCLKTYFGH SSFKPVQWKV IHSVLEERRD NVVVMATGYG 

       550        560        570        580        590        600 
KSLCFQYPPV YTGKIGIVIS PLISLMEDQV LQLELSNVPA CLLGSAQSKN ILGDVKLGKY 

       610        620        630        640        650        660 
RVIYITPEFC SGNLDLLQQL DSSIGITLIA VDEAHCISEW GHDFRSSFRM LGSLKTALPL 

       670        680        690        700        710        720 
VPVIALSATA SSSIREDIIS CLNLKDPQIT CTGFDRPNLY LEVGRKTGNI LQDLKPFLVR 

       730        740        750        760        770        780 
KASSAWEFEG PTIIYCPSRK MTEQVTAELG KLNLACRTYH AGMKISERKD VHHRFLRDEI 

       790        800        810        820        830        840 
QCVVATVAFG MGINKADIRK VIHYGAPKEM ESYYQEIGRA GRDGLQSSCH LLWAPADFNT 

       850        860        870        880        890        900 
SRNLLIEIHD EKFRLYKLKM MVKMEKYLHS SQCRRRIILS HFEDKCLQKA SLDIMGTEKC 

       910        920        930        940        950        960 
CDNCRPRLNH CLTANNSEDA SQDFGPQAFQ LLSAVDILQE KFGIGIPILF LRGSNSQRLP 

       970        980        990       1000       1010       1020 
DKYRGHRLFG AGKEQAESWW KTLSHHLIAE GFLVEVPKEN KYIKTCSLTK KGRKWLGEAS 

      1030       1040       1050       1060       1070       1080 
SQSPPSLLLQ ANEEMFPRKV LLPSSNPVSP ETTQHSSNQN PAGLTTKQSN LERTHSYKVP 

      1090       1100       1110       1120       1130       1140 
EKVSSGTNIP KKSAVMPSPG TSSSPLEPAI SAQELDARTG LYARLVEARQ KHANKMDVPP 

      1150       1160       1170       1180       1190       1200 
AILATNKVLL DMAKMRPTTV ENMKQIDGVS EGKAALLAPL LEVIKHFCQV TSVQTDLLSS 

      1210       1220       1230       1240       1250       1260 
AKPHKEQEKS QEMEKKDCSL PQSVAVTYTL FQEKKMPLHS IAENRLLPLT AAGMHLAQAV 

      1270       1280       1290       1300       1310       1320 
KAGYPLDMER AGLTPETWKI IMDVIRNPPI NSDMYKVKLI RMLVPENLDT YLIHMAIEIL 

      1330       1340       1350       1360       1370       1380 
QSGSDSRTQP PCDSSRKRRF PSSAESCESC KESKEAVTET KASSSESKRK LPEWFAKGNV 

      1390       1400 
PSADTGSSSS MAKTKKKGLF S 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of a mouse homologue of the human Werner syndrome gene and assignment to 8A4 by fluorescence in situ hybridization."
Imamura O., Ichikawa K., Yamabe Y., Goto M., Sugawara M., Furuichi Y.
Genomics 41:298-300(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Strain: BALB/c.
Tissue: Spleen and Testis.
[2]"Genomic structure of the human Werner's gene and cloning of its 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 (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]"Mutations in the WRN Gene in mice accelerate mortality in a p53-null background."
Lombard D.B., Beard C., Johnson B., Marciniak R.A., Dausman J., Bronson R., Buhlmann J.E., Lipman R., Curry R., Sharpe A., Jaenisch R., Guarente L.
Mol. Cell. Biol. 20:3286-3291(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
Tissue: Lymph node and Spleen.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[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]"A novel protein interacts with the Werner's syndrome gene product physically and functionally."
Kawabe Y., Branzei D., Hayashi T., Suzuki H., Masuko T., Onoda F., Heo S.-J., Ikeda H., Shimamoto A., Furuichi Y., Seki M., Enomoto T.
J. Biol. Chem. 276:20364-20369(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WRNIP1.
[8]"Probing the roles of active site residues in the 3'-5' exonuclease of the Werner syndrome protein."
Choi J.M., Kang S.Y., Bae W.J., Jin K.S., Ree M., Cho Y.
J. Biol. Chem. 282:9941-9951(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 31-238 IN COMPLEX WITH ZINC IONS AND SULFATE, SUBUNIT, FUNCTION, EXONUCLEASE ACTIVITY, ENZYME REGULATION, CIRCULAR DICHROISM, MUTAGENESIS OF LYS-185; ARG-190 AND TYR-206.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D86527 mRNA. Translation: BAA20270.1.
D86526 mRNA. Translation: BAA20269.1.
AF091215 mRNA. Translation: AAC78077.1.
AF091216 Genomic DNA. Translation: AAC72359.1.
AF241636 mRNA. Translation: AAF64490.1.
AC153789 Genomic DNA. No translation available.
AC115809 Genomic DNA. No translation available.
BC050921 mRNA. Translation: AAH50921.1.
BC060700 mRNA. Translation: AAH60700.1.
CCDSCCDS22229.1.
PIRT17452.
T30247.
RefSeqNP_001116294.1. NM_001122822.1.
NP_035851.3. NM_011721.4.
XP_006509154.1. XM_006509091.1.
XP_006509155.1. XM_006509092.1.
UniGeneMm.228805.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2E6LX-ray2.20A31-238[»]
2E6MX-ray2.00A31-238[»]
ProteinModelPortalO09053.
SMRO09053. Positions 37-225, 488-1200.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-27642N.

PTM databases

PhosphoSiteO09053.

Proteomic databases

PaxDbO09053.
PRIDEO09053.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000033990; ENSMUSP00000033990; ENSMUSG00000031583.
ENSMUST00000033991; ENSMUSP00000033991; ENSMUSG00000031583.
GeneID22427.
KEGGmmu:22427.
UCSCuc009ljw.1. mouse.

Organism-specific databases

CTD7486.
MGIMGI:109635. Wrn.

Phylogenomic databases

eggNOGCOG0514.
GeneTreeENSGT00550000074520.
HOGENOMHOG000146447.
HOVERGENHBG000325.
InParanoidQ80YP9.
KOK10900.
OMAGIEGDQW.
OrthoDBEOG7J70F2.
TreeFamTF312852.

Gene expression databases

ArrayExpressO09053.
BgeeO09053.
CleanExMM_WRN.
GenevestigatorO09053.

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

EvolutionaryTraceO09053.
NextBio302865.
PROO09053.
SOURCESearch...

Entry information

Entry nameWRN_MOUSE
AccessionPrimary (citable) accession number: O09053
Secondary accession number(s): O09050 expand/collapse secondary AC list , Q80YP9, Q9JKD4, Q9Z241, Q9Z242
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 131 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot