Reviewed, UniProtKB/Swiss-Prot Q14191 (WRN_HUMAN)

Names and origin

Protein names

Recommended name:
    Werner syndrome ATP-dependent helicase
    EC=3.6.1.-

Gene names

Name:	WRN
Synonyms:	RECQ3, RECQL2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1432 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Essential for the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity. May be involved in the control of genomic stability By similarity.
Subunit structure	Interacts via its N-terminal domain with WRNIP1 By similarity. Interacts with EXO1.
Subcellular location	Nucleus › nucleolus.
Post-translational modification	Phosphorylated by PRKDC. Phosphorylated upon DNA damage, probably by ATM or ATR.
Involvement in disease	Defects in WRN are a cause of Werner syndrome (WRN) [MIM:277700]. WRN is 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. Currently all known WS mutations produces prematurely terminated proteins. Defects in WRN may be a cause of colorectal cancer (CRC) [MIM:114500].
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
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Helicase Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA recombination Inferred from electronic annotation. Source: InterPro DNA synthesis during DNA repair Inferred from direct assay. Source: UniProtKB base-excision repair Inferred from direct assay. Source: UniProtKB multicellular organismal aging Ref.20 Inferred from mutant phenotype. Source: UniProtKB positive regulation of hydrolase activity Inferred from direct assay. Source: UniProtKB regulation of apoptosis Inferred from genetic interaction. Source: MGI replication fork processing Inferred from direct assay. Source: UniProtKB response to UV-C Inferred from direct assay. Source: UniProtKB response to oxidative stress Inferred from direct assay. Source: UniProtKB telomere maintenance Inferred from mutant phenotype. Source: UniProtKB
Cellular component	centrosome Inferred from direct assay. Source: UniProtKB nucleolus Ref.4 Inferred from direct assay. Source: UniProtKB nucleoplasm Inferred from direct assay. Source: MGI
Molecular function	3'-5' DNA helicase activity Inferred from direct assay. Source: UniProtKB 3'-5' exonuclease activity Inferred from direct assay. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: InterPro ATP-dependent DNA helicase activity Inferred from direct assay. Source: UniProtKB G-quadruplex DNA binding Inferred from direct assay. Source: UniProtKB Y-form DNA binding Inferred from direct assay. Source: UniProtKB bubble DNA binding Inferred from direct assay. Source: UniProtKB four-way junction helicase activity Inferred from direct assay. Source: UniProtKB protein complex binding Inferred from direct assay. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BLM	P54132	4	EBI-368417,EBI-621372
FEN1	P39748	7	EBI-368417,EBI-707816
PARP1	P09874	2	EBI-368417,EBI-355676
RAD52	P43351	4	EBI-368417,EBI-706448
RPA1	P27694	4	EBI-368417,EBI-621389
TERF2	Q15554	4	EBI-368417,EBI-706637
TP53	P04637	2	EBI-368417,EBI-366083
VCP	P55072	1	EBI-368417,EBI-355164
VCP	Q3ZBT1	1	EBI-368417,EBI-706432	From a different organism.

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

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

Motif

668 – 671

4

DEAH box

Compositional bias

507 – 510

4

Poly-Glu

Amino acid modifications

Modified residue

453

1

Phosphoserine

Modified residue

467

1

Phosphoserine

Modified residue

1058

1

Phosphoserine

Modified residue

1141

1

Phosphoserine

Natural variations

Natural variant

32

1

K → R

VAR_017453

Natural variant

92

1

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

VAR_036318

Natural variant

114

1

V → I: dbSNP rs2230009.

VAR_017454

Natural variant

125

1

K → N in WRN.

VAR_026588

Natural variant

135

1

K → E in WRN.

VAR_026589

Natural variant

172

1

T → P

VAR_017455

Natural variant

240

1

N → K

VAR_017456

Natural variant

324

1

T → A: dbSNP rs1800390.

VAR_006904

Natural variant

329

1

Q → R: dbSNP rs4987237.

VAR_020450

Natural variant

343

1

E → K: dbSNP rs11574222.

VAR_018941

Natural variant

383

1

L → F: dbSNP rs4987238.

VAR_020451

Natural variant

383

1

L → W

VAR_017457

Natural variant

387

1

M → I: dbSNP rs1800391.

VAR_006905

Natural variant

533

1

N → S: dbSNP rs11574240.

VAR_018942

Natural variant

612

1

S → C: dbSNP rs11574250.

VAR_018943

Natural variant

708

1

S → F: dbSNP rs11574289.

VAR_018944

Natural variant

724

1

Q → L

VAR_017458

Natural variant

834

1

R → C: dbSNP rs3087425.

VAR_014913

Natural variant

912

1

I → S: dbSNP rs11574323.

VAR_018945

Natural variant

1074

1

F → L: dbSNP rs2725362.

VAR_007903

Natural variant

1079

1

S → L: dbSNP rs3087414.

VAR_014914

Natural variant

1133

1

S → A: dbSNP rs11574358.

VAR_018946

Natural variant

1269

1

K → E

VAR_017459

Natural variant

1339

1

V → I: dbSNP rs11574395.

VAR_018947

Natural variant

1367

1

C → R Polymorphism associated with a higher risk of myocardial infarction. dbSNP rs1346044.

VAR_006906

Secondary structure

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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 – 168

8

Helix

177 – 185

9

Helix

193 – 196

4

Beta strand

202 – 204

3

Helix

207 – 229

23

Beta strand

955 – 958

4

Helix

960 – 972

13

Turn

973 – 975

3

Helix

980 – 986

7

Helix

993 – 997

5

Turn

1002 – 1005

4

Helix

1006 – 1009

4

Helix

1012 – 1025

14

Beta strand

1026 – 1031

6

Turn

1036 – 1038

3

Beta strand

1040 – 1043

4

Helix

1045 – 1053

9

Turn

1054 – 1057

4

Beta strand

1062 – 1064

3

Helix

1147 – 1170

24

Helix

1175 – 1178

4

Helix

1181 – 1190

10

Helix

1195 – 1198

4

Helix

1206 – 1211

6

Helix

1213 – 1225

13

Sequences

	Sequence		Length	Mass (Da)