O09053 (WRN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Werner syndrome ATP-dependent helicase homolog
EC=3.6.4.12

Alternative name(s):
Exonuclease WRN
EC=3.1.-.-

Gene names

Name:

Wrn

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1401 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Nucleus › nucleolus By similarity. Nucleus › nucleoplasm 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 process	DNA damage DNA repair
Cellular component	Nucleus
Ligand	ATP-binding DNA-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Exonuclease Helicase Hydrolase Nuclease
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	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: Compara base-excision repair Inferred from electronic annotation. Source: Compara 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 nucleolus to nucleoplasm transport Inferred from sequence orthology PubMed 11420665. Source: MGI positive regulation of hydrolase activity Inferred from electronic annotation. Source: Compara regulation of apoptotic process Inferred from electronic annotation. Source: Compara regulation of growth rate Inferred from mutant phenotype PubMed 12707040. Source: MGI replication fork processing Inferred from electronic annotation. Source: Compara replicative cell aging Inferred from mutant phenotype Ref.3. Source: MGI response to UV-C Inferred from electronic annotation. Source: Compara response to oxidative stress Inferred from electronic annotation. Source: Compara telomere maintenance Inferred from mutant phenotype PubMed 12707040. Source: MGI
Cellular_component	MutLalpha complex Inferred from electronic annotation. Source: Compara centrosome Inferred from electronic annotation. Source: Compara nucleolus Inferred from sequence orthology PubMed 11420665. Source: MGI nucleoplasm Inferred from direct assay PubMed 11420665. Source: MGI
Molecular_function	3'-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: Compara Y-form DNA binding Inferred from electronic annotation. Source: Compara bubble DNA binding Inferred from electronic annotation. Source: Compara four-way junction helicase activity Inferred from electronic annotation. Source: Compara magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB manganese ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1401

1401

Werner syndrome ATP-dependent helicase homolog

PRO_0000205046

Regions

Domain

51 – 223

173

3'-5' exonuclease

Domain

522 – 688

167

Helicase ATP-binding

Domain

713 – 866

154

Helicase C-terminal

Domain

1115 – 1194

80

HRDC

Nucleotide binding

535 – 542

8

ATP By similarity

Region

1 – 271

271

Interaction with WRNIP1

Region

952 – 958

7

Interaction with DNA By similarity

Motif

632 – 635

4

DEAH box

Compositional bias

1387 – 1390

4

Poly-Ser

Sites

Metal binding

76

1

Magnesium 1; catalytic

Metal binding

76

1

Magnesium 2; catalytic

Metal binding

78

1

Magnesium 1; catalytic

Metal binding

210

1

Magnesium 1; catalytic

Site

139

1

Interaction with DNA By similarity

Site

1002

1

Interaction with DNA By similarity

Amino acid modifications

Modified residue

419

1

Phosphoserine By similarity

Modified residue

433

1

Phosphoserine By similarity

Modified residue

1098

1

Phosphoserine By similarity

Experimental info

Mutagenesis

185

1

K → A: Loss of exonuclease activity. Ref.8

Mutagenesis

190

1

R → A: Strongly reduced exonuclease activity. Ref.8

Mutagenesis

206

1

Y → F: Loss of exonuclease activity. Ref.8

Sequence conflict

101

1

S → N in BAA20269. Ref.1

Sequence conflict

101

1

S → N in BAA20270. Ref.1

Sequence conflict

101

1

S → N in AAC72359. Ref.2

Sequence conflict

101

1

S → N in AAF64490. Ref.3

Sequence conflict

228

1

A → V in BAA20269. Ref.1

Sequence conflict

228

1

A → V in BAA20270. Ref.1

Sequence conflict

228

1

A → V in AAC72359. Ref.2

Sequence conflict

228

1

A → V in AAF64490. Ref.3

Sequence conflict

250

1

S → L in BAA20269. Ref.1

Sequence conflict

250

1

S → L in BAA20270. Ref.1

Sequence conflict

250

1

S → L in AAC72359. Ref.2

Sequence conflict

250

1

S → L in AAF64490. Ref.3

Sequence conflict

452

1

V → M in BAA20269. Ref.1

Sequence conflict

452

1

V → M in BAA20270. Ref.1

Sequence conflict

452

1

V → M in AAC72359. Ref.2

Sequence conflict

452

1

V → M in AAF64490. Ref.3

Sequence conflict

459

1

T → K in BAA20269. Ref.1

Sequence conflict

459

1

T → K in BAA20270. Ref.1

Sequence conflict

459

1

T → K in AAC72359. Ref.2

Sequence conflict

459

1

T → K in AAF64490. Ref.3

Sequence conflict

468

1

R → C in BAA20269. Ref.1

Sequence conflict

468

1

R → C in BAA20270. Ref.1

Sequence conflict

468

1

R → C in AAC72359. Ref.2

Sequence conflict

468

1

R → C in AAF64490. Ref.3

Sequence conflict

619

1

Q → K in BAA20269. Ref.1

Sequence conflict

619

1

Q → K in BAA20270. Ref.1

Sequence conflict

619

1

Q → K in AAC72359. Ref.2

Sequence conflict

619

1

Q → K in AAF64490. Ref.3

Sequence conflict

800

1

K → Q in BAA20270. Ref.1

Sequence conflict

800

1

K → Q in BAA20269. Ref.1

Sequence conflict

844

1

L → H in AAC72359. Ref.2

Sequence conflict

955 – 988

34

NSQRL…SHHLI → VSVSVIAPGTVSDSAFHCVA MALAFFRWLTSNPC in AAC72359. Ref.2

Sequence conflict

1021

1

S → L in BAA20269. Ref.1

Sequence conflict

1021

1

S → L in BAA20270. Ref.1

Sequence conflict

1021

1

S → L in AAF64490. Ref.3

Sequence conflict

1145

1

T → A in BAA20270. Ref.1

Sequence conflict

1145

1

T → A in BAA20269. Ref.1

Sequence conflict

1181

1

L → V in BAA20270. Ref.1

Sequence conflict

1181

1

L → V in BAA20269. Ref.1

Sequence conflict

1182

1

E → G in BAA20269. Ref.1

Sequence conflict

1182

1

E → G in BAA20270. Ref.1

Sequence conflict

1182

1

E → G in AAF64490. Ref.3

Sequence conflict

1252

1

A → V in BAA20269. Ref.1

Sequence conflict

1252

1

A → V in BAA20270. Ref.1

Sequence conflict

1252

1

A → V in AAF64490. Ref.3

Sequence conflict

1308

1

L → I in BAA20269. Ref.1

Sequence conflict

1308

1

L → I in BAA20270. Ref.1

Sequence conflict

1308

1

L → I in AAF64490. Ref.3

Sequence conflict

1356

1

A → V in BAA20269. Ref.1

Sequence conflict

1356

1

A → V in BAA20270. Ref.1

Sequence conflict

1356

1

A → V in AAF64490. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

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.

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.

.

.

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.

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.

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.

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1401

Helix Strand Turn

Details...

Beta strand

45 – 50

6

Helix

53 – 66

14

Beta strand

72 – 78

7

Beta strand

93 – 97

5

Beta strand

99 – 106

8

Helix

108 – 110

3

Helix

116 – 122

7

Beta strand

127 – 133

7

Helix

134 – 145

12

Beta strand

151 – 154

4

Helix

155 – 162

8

Helix

171 – 179

9

Helix

187 – 190

4

Beta strand

196 – 198

3

Helix

201 – 222

22

Sequences

	Sequence		Length	Mass (Da)
	O09053 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 66DF2252B17C24C3	FASTA	1,401	157,204
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00113830.

PIR

T17452.
T30247.

RefSeq

NP_001116294.1. NM_001122822.1.
NP_035851.3. NM_011721.4.

UniGene

Mm.228805.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2E6L	X-ray	2.20	A	31-238	[»]
2E6M	X-ray	2.00	A	31-238	[»]

ProteinModelPortal

O09053.

SMR

O09053. Positions 37-225, 495-1058, 1107-1200.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27642N.

PTM databases

PhosphoSite

O09053.

Proteomic databases

PaxDb

O09053.

PRIDE

O09053.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000033990; ENSMUSP00000033990; ENSMUSG00000031583.
ENSMUST00000033991; ENSMUSP00000033991; ENSMUSG00000031583.

GeneID

22427.

KEGG

mmu:22427.

Organism-specific databases

CTD

7486.

MGI

MGI:109635. Wrn.

Phylogenomic databases

eggNOG

COG0514.

GeneTree

ENSGT00550000074520.

HOGENOM

HOG000146447.

HOVERGEN

HBG000325.

InParanoid

Q80YP9.

KO

K10900.

OMA

GIEGDQW.

OrthoDB

EOG4DNF3J.

Gene expression databases

ArrayExpress

O09053.

Bgee

O09053.

CleanEx

MM_WRN.

Genevestigator

O09053.

GermOnline

ENSMUSG00000031583. Mus musculus.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.
1.10.150.80. 1 hit.

InterPro

IPR002562. 3'-5'_exonuclease_dom.
IPR011545. DNA/RNA_helicase_DEAD/DEAH_N.
IPR004589. DNA_helicase_ATP-dep_RecQ.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR010997. HRDC-like.
IPR002121. HRDC_dom.
IPR012337. RNaseH-like_dom.
IPR018982. RQC_domain.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF00270. DEAD. 1 hit.
PF01612. DNA_pol_A_exo1. 1 hit.
PF00271. Helicase_C. 1 hit.
PF00570. HRDC. 1 hit.
PF09382. RQC. 1 hit.
[Graphical view]

SMART

SM00474. 35EXOc. 1 hit.
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SM00341. HRDC. 1 hit.
SM00956. RQC. 1 hit.
[Graphical view]

SUPFAM

SSF47819. HRDC_like. 1 hit.
SSF53098. RNaseH_fold. 1 hit.

TIGRFAMs

TIGR00614. recQ_fam. 1 hit.

PROSITE

PS00690. DEAH_ATP_HELICASE. False negative.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS50967. HRDC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O09053.

NextBio

302865.

SOURCE

Search...

Entry information

Entry name

WRN_MOUSE

Accession

Primary (citable) accession number: O09053
Secondary accession number(s): O09050 , Q80YP9, Q9JKD4, Q9Z241, Q9Z242

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 121 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program