Q14191 (WRN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1432 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. Ref.8 Ref.12 Ref.14 Ref.16 Ref.17 Ref.20
Catalytic activity	ATP + H2O = ADP + phosphate. Ref.23
Cofactor	Binds 2 magnesium ions per subunit. Has high activity with manganese and zinc ions (in vitro). Ref.23
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.20 Ref.27
Subcellular location	Nucleus › nucleolus. Nucleus. Nucleus › nucleoplasm. Note: Gamma-irradiation leads to its translocation from nucleoli to nucleoplasm and PML regulates the irradiation-induced WRN relocation. Ref.6 Ref.12 Ref.16 Ref.20
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.34 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 process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat
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 Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	DNA recombination Inferred from electronic annotation. Source: InterPro DNA synthesis involved in DNA repair Inferred from direct assay Ref.12. 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 gamma radiation Inferred from direct assay Ref.20. Source: UniProtKB cellular response to starvation Inferred from direct assay PubMed 11420665. Source: MGI double-strand break repair Inferred from mutant phenotype Ref.20. Source: UniProtKB multicellular organismal aging Inferred from mutant phenotype Ref.34. Source: UniProtKB 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: Compara replication fork processing Inferred from direct assay PubMed 17115688. Source: UniProtKB replicative cell aging Inferred from electronic annotation. Source: Compara 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_component	centrosome Inferred from direct assay PubMed 17498979. Source: UniProtKB nucleolus Inferred from direct assay PubMed 12181313Ref.20Ref.6. Source: UniProtKB nucleoplasm Inferred from direct assay Ref.20. Source: UniProtKB
Molecular_function	3'-5' DNA helicase activity Inferred from direct assay PubMed 17715146. Source: UniProtKB 3'-5' exonuclease activity Inferred from direct assay PubMed 10783163PubMed 12181313Ref.23. 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 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 four-way junction helicase activity Inferred from direct assay PubMed 11433031. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.23. Source: UniProtKB manganese ion binding Inferred from direct assay Ref.23. 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BLM	P54132	9	EBI-368417,EBI-621372
FEN1	P39748	10	EBI-368417,EBI-707816
PARP1	P09874	6	EBI-368417,EBI-355676
RAD52	P43351	9	EBI-368417,EBI-706448
RPA1	P27694	8	EBI-368417,EBI-621389
SIRT1	Q96EB6	9	EBI-368417,EBI-1802965
TERF2	Q15554	8	EBI-368417,EBI-706637
TP53	P04637	5	EBI-368417,EBI-366083
XRCC6	P12956	7	EBI-368417,EBI-353208

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1432

1432

Werner syndrome ATP-dependent helicase

PRO_0000205045

Regions

Domain

60 – 228

169

3'-5' exonuclease

Repeat

424 – 450

27

1

Repeat

451 – 477

27

2

Domain

558 – 724

167

Helicase ATP-binding

Domain

749 – 899

151

Helicase C-terminal

Domain

1150 – 1229

80

HRDC

Nucleotide binding

571 – 578

8

ATP By similarity

Region

1 – 277

277

Interaction with WRNIP1 By similarity

Region

424 – 477

54

2 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

Region

987 – 993

7

Interaction with DNA

Motif

668 – 671

4

DEAH box

Compositional bias

507 – 510

4

Poly-Glu

Sites

Metal binding

82

1

Magnesium 1; catalytic

Metal binding

82

1

Magnesium 2; catalytic

Metal binding

84

1

Magnesium 1; catalytic

Metal binding

216

1

Magnesium 1; catalytic

Site

145

1

Interaction with DNA Probable

Site

1037

1

Interaction with DNA

Amino acid modifications

Modified residue

426

1

Phosphoserine Ref.18

Modified residue

440

1

Phosphoserine Ref.15 Ref.18

Modified residue

453

1

Phosphoserine Ref.18

Modified residue

467

1

Phosphoserine Ref.15 Ref.18

Modified residue

1133

1

Phosphoserine Ref.21

Natural variations

Natural variant

32

1

K → R. Ref.33
Corresponds to variant rs34477820 [ dbSNP | Ensembl ].

VAR_017453

Natural variant

92

1

G → V in a colorectal cancer sample; somatic mutation. Ref.35

VAR_036318

Natural variant

114

1

V → I No effect on exonuclease activity. Ref.4 Ref.23 Ref.33
Corresponds to variant rs2230009 [ dbSNP | Ensembl ].

VAR_017454

Natural variant

125

1

K → N in WRN. Ref.34

VAR_026588

Natural variant

135

1

K → E in WRN. Ref.34

VAR_026589

Natural variant

172

1

T → P No effect on exonuclease activity. Ref.23 Ref.33

VAR_017455

Natural variant

240

1

N → K. Ref.33

VAR_017456

Natural variant

324

1

T → A. Ref.32
Corresponds to variant rs1800390 [ dbSNP | Ensembl ].

VAR_006904

Natural variant

329

1

Q → R.
Corresponds to variant rs4987237 [ dbSNP | Ensembl ].

VAR_020450

Natural variant

343

1

E → K. Ref.4
Corresponds to variant rs11574222 [ dbSNP | Ensembl ].

VAR_018941

Natural variant

383

1

L → F.
Corresponds to variant rs4987238 [ dbSNP | Ensembl ].

VAR_020451

Natural variant

383

1

L → W. Ref.33

VAR_017457

Natural variant

387

1

M → I. Ref.4 Ref.30 Ref.31 Ref.33
Corresponds to variant rs1800391 [ dbSNP | Ensembl ].

VAR_006905

Natural variant

533

1

N → S. Ref.4
Corresponds to variant rs11574240 [ dbSNP | Ensembl ].

VAR_018942

Natural variant

612

1

S → C. Ref.4
Corresponds to variant rs11574250 [ dbSNP | Ensembl ].

VAR_018943

Natural variant

708

1

S → F. Ref.4
Corresponds to variant rs11574289 [ dbSNP | Ensembl ].

VAR_018944

Natural variant

711

1

R → W.
Corresponds to variant rs34560788 [ dbSNP | Ensembl ].

VAR_057124

Natural variant

724

1

Q → L. Ref.33

VAR_017458

Natural variant

834

1

R → C. Ref.4
Corresponds to variant rs3087425 [ dbSNP | Ensembl ].

VAR_014913

Natural variant

912

1

I → S. Ref.4
Corresponds to variant rs11574323 [ dbSNP | Ensembl ].

VAR_018945

Natural variant

1074

1

L → F. Ref.1 Ref.2 Ref.3 Ref.30 Ref.33
Corresponds to variant rs1801195 [ dbSNP | Ensembl ].

VAR_007903

Natural variant

1079

1

S → L. Ref.4
Corresponds to variant rs3087414 [ dbSNP | Ensembl ].

VAR_014914

Natural variant

1133

1

S → A. Ref.4
Corresponds to variant rs11574358 [ dbSNP | Ensembl ].

VAR_018946

Natural variant

1141

1

S → L. Ref.36

VAR_054162

Natural variant

1269

1

K → E. Ref.33

VAR_017459

Natural variant

1339

1

V → I. Ref.4
Corresponds to variant rs11574395 [ dbSNP | Ensembl ].

VAR_018947

Natural variant

1367

1

C → R Polymorphism associated with a higher risk of myocardial infarction. Ref.4 Ref.28 Ref.32 Ref.33
Corresponds to variant rs1346044 [ dbSNP | Ensembl ].

VAR_006906

Experimental info

Mutagenesis

84

1

E → A: Abolishes exonuclease activity. Ref.8 Ref.23

Mutagenesis

88

1

L → A: No effect on exonuclease activity.

Mutagenesis

145

1

W → A: Reduces exonuclease activity. Ref.23

Mutagenesis

212

1

Y → F: Strongly reduces exonuclease activity. Ref.23

Mutagenesis

987

1

R → A: Reduces affinity for DNA about 8-fold. Loss of DNA binding; when associated with A-993. Ref.27

Mutagenesis

989

1

S → A: Reduces affinity for DNA about 4-fold. Ref.27

Mutagenesis

993

1

R → A: Reduces affinity for DNA about 20-fold. Loss of DNA binding; when associated with A-987. Ref.27

Mutagenesis

993

1

R → E: Loss of DNA binding. Ref.27

Mutagenesis

1037

1

F → A: Reduces affinity for DNA about 8-fold. Ref.27

Mutagenesis

1038

1

M → A: Reduces affinity for DNA about 4-fold. Ref.27

Secondary structure

1

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1432

Helix Strand Turn

Details...

Helix

39 – 41

3

Beta strand

51 – 56

6

Helix

59 – 72

14

Beta strand

78 – 84

7

Beta strand

99 – 105

7

Beta strand

108 – 112

5

Helix

114 – 116

3

Beta strand

117 – 119

3

Helix

122 – 128

7

Beta strand

133 – 139

7

Helix

140 – 151

12

Beta strand

157 – 160

4

Helix

161 – 169

9

Helix

177 – 185

9

Helix

193 – 196

4

Beta strand

202 – 204

3

Helix

207 – 228

22

Beta strand

955 – 958

4

Helix

960 – 972

13

Turn

973 – 975

3

Helix

980 – 986

7

Helix

996 – 1000

5

Turn

1002 – 1009

8

Helix

1012 – 1024

13

Beta strand

1027 – 1032

6

Turn

1036 – 1038

3

Beta strand

1039 – 1043

5

Helix

1045 – 1054

10

Beta strand

1062 – 1064

3

Helix

1147 – 1171

25

Helix

1175 – 1178

4

Helix

1181 – 1190

10

Helix

1195 – 1198

4

Beta strand

1201 – 1203

3

Helix

1206 – 1211

6

Helix

1213 – 1225

13

Sequences

	Sequence		Length	Mass (Da)
	Q14191 [UniParc]. Last modified February 8, 2011. Version 2. Checksum: 63F10D19E90AA461	FASTA	1,432	162,461
	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

References

	« Hide 'large scale' referencesShow '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. , 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, EXONUCLEASE ACTIVITY, 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"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.
[17]	"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.
[18]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[19]	"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].
[20]	"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. Biokhimiia 76:550-554(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PML.
[21]	"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, MASS SPECTROMETRY.
[22]	"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.
[23]	"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, MASS SPECTROMETRY, CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF GLU-84; TRP-145 AND TYR-212, CHARACTERIZATION OF VARIANTS ILE-114 AND PRO-172.
[24]	"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.
[25]	"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.
[26]	"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, MASS SPECTROMETRY, CIRCULAR DICHROISM.
[27]	"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.
[28]	"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.
[29]	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)
[30]	"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.
[31]	"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.
[32]	"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.
[33]	"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.
[34]	"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. , 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.
[35]	"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. , 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.
[36]	"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. , 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.

Web resources

WRN

WRN mutation db (Warner disease)

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

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.

IPI

IPI00029107.

RefSeq

NP_000544.2. NM_000553.4.

UniGene

Hs.632050.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AXL	NMR	-	A	949-1092	[»]
2DGZ	NMR	-	A	1140-1239	[»]
2E1E	X-ray	2.30	A	1142-1242	[»]
2E1F	X-ray	2.00	A	1142-1242	[»]
2FBT	X-ray	2.05	A	38-236	[»]
2FBV	X-ray	2.40	A	38-236	[»]
2FBX	X-ray	2.20	A	38-236	[»]
2FBY	X-ray	2.00	A	38-236	[»]
2FC0	X-ray	2.00	A	38-236	[»]
3AAF	X-ray	1.90	A/B	949-1079	[»]

DisProt

DP00443.

ProteinModelPortal

Q14191.

SMR

Q14191. Positions 38-231, 540-1092, 1142-1235.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31380N.

IntAct

Q14191. 15 interactions.

MINT

MINT-95856.

STRING

9606.ENSP00000298139.

PTM databases

PhosphoSite

Q14191.

Polymorphism databases

DMDM

6136393.

Proteomic databases

PaxDb

Q14191.

PRIDE

Q14191.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000298139; ENSP00000298139; ENSG00000165392.

GeneID

7486.

KEGG

hsa:7486.

UCSC

uc003xio.4. human.

Organism-specific databases

CTD

7486.

GeneCards

GC08P030948.

H-InvDB

HIX0007441.

HGNC

HGNC:12791. WRN.

HPA

HPA028661.

MIM

114500. phenotype.
277700. phenotype.
604611. gene.

neXtProt

NX_Q14191.

Orphanet

902. Werner syndrome.

PharmGKB

PA367.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0514.

HOGENOM

HOG000146447.

HOVERGEN

HBG000325.

InParanoid

Q14191.

KO

K10900.

OMA

GIEGDQW.

OrthoDB

EOG4DNF3J.

PhylomeDB

Q14191.

Enzyme and pathway databases

Pathway_Interaction_DB

telomerasepathway. Regulation of Telomerase.

Gene expression databases

Bgee

Q14191.

CleanEx

HS_WRN.

Genevestigator

Q14191.

GermOnline

ENSG00000165392. Homo sapiens.

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.
IPR027417. P-loop_NTPase.
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.
SSF52540. SSF52540. 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

Q14191.

GenomeRNAi

7486.

NextBio

29326.

SOURCE

Search...

Entry information

Entry name

WRN_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 153 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.