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Reviewed, UniProtKB/Swiss-Prot Q14191 (WRN_HUMAN)

Last modified November 25, 2008. Version 103. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Werner syndrome ATP-dependent helicase
    EC=3.6.1.-
Gene names
Name: WRN
Synonyms: RECQ3, RECQL2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1432 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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

Nucleusnucleolus.

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 componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainRepeat
   LigandATP-binding
DNA-binding
Nucleotide-binding
   Molecular functionHelicase
Hydrolase
   PTMPhosphoprotein
   Technical term3D-structure

Gene Ontology (GO)

   Biological processDNA 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 componentcentrosome

Inferred from direct assay. Source: UniProtKB

nucleolus Ref.4

Inferred from direct assay. Source: UniProtKB

nucleoplasm

Inferred from direct assay. Source: MGI

   Molecular function3'-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...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14321432Werner syndrome ATP-dependent helicase
PRO_0000205045

Regions

Repeat424 – 450271
Repeat451 – 477272
Domain558 – 724167Helicase ATP-binding
Domain749 – 899151Helicase C-terminal
Domain1150 – 122980HRDC
Nucleotide binding571 – 5788ATP By similarity
Region1 – 277277Interaction 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
Motif668 – 6714DEAH box
Compositional bias507 – 5104Poly-Glu

Amino acid modifications

Modified residue4531Phosphoserine
Modified residue4671Phosphoserine
Modified residue10581Phosphoserine
Modified residue11411Phosphoserine

Natural variations

Natural variant321K → R
VAR_017453
Natural variant921G → V in a colorectal cancer sample; somatic mutation.
VAR_036318
Natural variant1141V → I: dbSNP rs2230009.
VAR_017454
Natural variant1251K → N in WRN.
VAR_026588
Natural variant1351K → E in WRN.
VAR_026589
Natural variant1721T → P
VAR_017455
Natural variant2401N → K
VAR_017456
Natural variant3241T → A: dbSNP rs1800390.
VAR_006904
Natural variant3291Q → R: dbSNP rs4987237.
VAR_020450
Natural variant3431E → K: dbSNP rs11574222.
VAR_018941
Natural variant3831L → F: dbSNP rs4987238.
VAR_020451
Natural variant3831L → W
VAR_017457
Natural variant3871M → I: dbSNP rs1800391.
VAR_006905
Natural variant5331N → S: dbSNP rs11574240.
VAR_018942
Natural variant6121S → C: dbSNP rs11574250.
VAR_018943
Natural variant7081S → F: dbSNP rs11574289.
VAR_018944
Natural variant7241Q → L
VAR_017458
Natural variant8341R → C: dbSNP rs3087425.
VAR_014913
Natural variant9121I → S: dbSNP rs11574323.
VAR_018945
Natural variant10741F → L: dbSNP rs2725362.
VAR_007903
Natural variant10791S → L: dbSNP rs3087414.
VAR_014914
Natural variant11331S → A: dbSNP rs11574358.
VAR_018946
Natural variant12691K → E
VAR_017459
Natural variant13391V → I: dbSNP rs11574395.
VAR_018947
Natural variant13671C → R Polymorphism associated with a higher risk of myocardial infarction. dbSNP rs1346044.
VAR_006906

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools