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WRN (Werner syndrome, RecQ helicase-like)

Identity

HGNC (Hugo) WRN
LocusID (NCBI) 7486
Location 8p12
Location_base_pair Starts at 30890778 and ends at 31031277 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Transcription 4.4 kb mRNA

Protein

Description 1432 amino acids; contains one ATP binding site, one DExH helicase box, one exonuclease domain unique among known RecQ helicases in the N-terminal region, a nuclear localization signal in the C-terminus and a direct repeat of 27 amino acids between the exonuclease and helicase domains.
Localisation nuclear, predominant nucleolar localization.
Function 3-5 DNA helicase; 3-5 exonuclease; functionally interacts with DNA polymerase delta (POLD1) and RPA which are required for DNA replication and DNA repair, with Ku which is involved in double strand DNA break repair by non-homologous DNA end joining, and with p53.
Homology Homologous to RecQ helicases, a subfamily of DExH box-containing DNA and RNA helicases. In particular, similarities with the four known human members in the RecQ subfamily, human RecQL, human BLM, the product of the Bloom syndrome gene, and the recently identified human RecQL4, involved in the Rothmund-Thomson syndrome, and RecQL5 proteins

Mutations

Germinal WRN mutations are located over the entire gene and include stop codons, insertions/deletions and exon deletions: not a single missense mutation has been identified so far.

Implicated in

Entity Werner syndrome
Disease Uncommon autosomal recessive disorder characterized by early onset of geriatric diseases, including atherosclerosis, osteoporosis, diabetes mellitus, juvenile cataract, graying of the hair and neoplasia, in particular soft-tissue sarcomas, in approximately 10% of WS patients.
Prognosis WS patients die at mean age 46 +/- 11,6 years due to malignant tumors or cardiovascular infarctions.
Cytogenetics Reciprocal chromosomal translocations and extensive genomic deletions.
  

External links

Nomenclature
HGNC (Hugo)WRN   12791
Cards
AtlasWRNID284
Entrez_Gene (NCBI)WRN  7486  Werner syndrome, RecQ helicase-like
GeneCards (Weizmann)WRN
Ensembl (Hinxton)ENSG00000165392 [Gene_View]  chr8:30890778-31031277 [Contig_View]  WRN [Vega]
ICGC DataPortalENSG00000165392
cBioPortalWRN
AceView (NCBI)WRN
Genatlas (Paris)WRN
WikiGenes7486
SOURCE (Princeton)NM_000553
Genomic and cartography
GoldenPath (UCSC)WRN  -  8p12   chr8:30890778-31031277 +  8p12   [Description]    (hg19-Feb_2009)
EnsemblWRN - 8p12 [CytoView]
Mapping of homologs : NCBIWRN [Mapview]
OMIM277700   604611   
Gene and transcription
Genbank (Entrez)AB209652 AF091214 AL833572 AY818673 BP279291
RefSeq transcript (Entrez)NM_000553
RefSeq genomic (Entrez)AC_000140 NC_000008 NC_018919 NG_008870 NT_167187 NW_001839128 NW_004929337
Consensus coding sequences : CCDS (NCBI)WRN
Cluster EST : UnigeneHs.632050 [ NCBI ]
CGAP (NCI)Hs.632050
Alternative Splicing : Fast-db (Paris)GSHG0028930
Alternative Splicing GalleryENSG00000165392
Gene ExpressionWRN [ NCBI-GEO ]     WRN [ SEEK ]   WRN [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ14191 (Uniprot)
NextProtQ14191  [Medical]
With graphics : InterProQ14191
Splice isoforms : SwissVarQ14191 (Swissvar)
Catalytic activity : Enzyme3.6.4.12 [ Enzyme-Expasy ]   3.6.4.123.6.4.12 [ IntEnz-EBI ]   3.6.4.12 [ BRENDA ]   3.6.4.12 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)DEAH_ATP_HELICASE (PS00690)    HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)    HRDC (PS50967)   
Domains : Interpro (EBI)3'-5'_exonuclease_dom [organisation]   DNA/RNA_helicase_DEAD/DEAH_N [organisation]   DNA_helicase_ATP-dep_RecQ [organisation]   Helicase_ATP-bd [organisation]   Helicase_C [organisation]   HRDC-like [organisation]   HRDC_dom [organisation]   P-loop_NTPase [organisation]   RNaseH-like_dom [organisation]   RQC_domain [organisation]   WHTH_DNA-bd_dom [organisation]  
Related proteins : CluSTrQ14191
Domain families : Pfam (Sanger)DEAD (PF00270)    DNA_pol_A_exo1 (PF01612)    Helicase_C (PF00271)    HRDC (PF00570)    RQC (PF09382)   
Domain families : Pfam (NCBI)pfam00270    pfam01612    pfam00271    pfam00570    pfam09382   
Domain families : Smart (EMBL)35EXOc (SM00474)  DEXDc (SM00487)  HELICc (SM00490)  HRDC (SM00341)  RQC (SM00956)  
DMDM Disease mutations7486
Blocks (Seattle)Q14191
PDB (SRS)2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
PDB (PDBSum)2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
PDB (IMB)2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
PDB (RSDB)2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0    3AAF   
Human Protein AtlasENSG00000165392 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ14191
HPRD05212
IPIIPI00029107   
Protein Interaction databases
DIP (DOE-UCLA)Q14191
IntAct (EBI)Q14191
FunCoupENSG00000165392
BioGRIDWRN
InParanoidQ14191
Interologous Interaction database Q14191
IntegromeDBWRN
STRING (EMBL)WRN
Ontologies - Pathways
Ontology : AmiGOmagnesium ion binding  Y-form DNA binding  bubble DNA binding  telomere maintenance  DNA synthesis involved in DNA repair  replicative cell aging  DNA binding  DNA helicase activity  DNA helicase activity  ATP-dependent DNA helicase activity  helicase activity  exonuclease activity  protein binding  ATP binding  nucleus  nucleoplasm  nucleolus  nucleolus  centrosome  ATP catabolic process  DNA metabolic process  DNA replication  base-excision repair  double-strand break repair  DNA recombination  cellular response to DNA damage stimulus  response to oxidative stress  aging  cell aging  3'-5' exonuclease activity  cellular response to starvation  four-way junction helicase activity  response to UV-C  multicellular organismal aging  ATPase activity  manganese ion binding  replication fork processing  replication fork processing  nucleolus to nucleoplasm transport  MutLalpha complex  protein complex binding  DNA duplex unwinding  DNA duplex unwinding  regulation of growth rate  protein homodimerization activity  regulation of apoptotic process  3'-5' DNA helicase activity  ATP-dependent 3'-5' DNA helicase activity  positive regulation of hydrolase activity  G-quadruplex DNA binding  cellular response to gamma radiation  
Ontology : EGO-EBImagnesium ion binding  Y-form DNA binding  bubble DNA binding  telomere maintenance  DNA synthesis involved in DNA repair  replicative cell aging  DNA binding  DNA helicase activity  DNA helicase activity  ATP-dependent DNA helicase activity  helicase activity  exonuclease activity  protein binding  ATP binding  nucleus  nucleoplasm  nucleolus  nucleolus  centrosome  ATP catabolic process  DNA metabolic process  DNA replication  base-excision repair  double-strand break repair  DNA recombination  cellular response to DNA damage stimulus  response to oxidative stress  aging  cell aging  3'-5' exonuclease activity  cellular response to starvation  four-way junction helicase activity  response to UV-C  multicellular organismal aging  ATPase activity  manganese ion binding  replication fork processing  replication fork processing  nucleolus to nucleoplasm transport  MutLalpha complex  protein complex binding  DNA duplex unwinding  DNA duplex unwinding  regulation of growth rate  protein homodimerization activity  regulation of apoptotic process  3'-5' DNA helicase activity  ATP-dependent 3'-5' DNA helicase activity  positive regulation of hydrolase activity  G-quadruplex DNA binding  cellular response to gamma radiation  
Protein Interaction DatabaseWRN
Wikipedia pathwaysWRN
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)WRN
snp3D : Map Gene to Disease7486
SNP (GeneSNP Utah)WRN
SNP : HGBaseWRN
Genetic variants : HAPMAPWRN
Exome VariantWRN
1000_GenomesWRN 
ICGC programENSG00000165392 
Cancer Gene: CensusWRN 
Somatic Mutations in Cancer : COSMICWRN 
CONAN: Copy Number AnalysisWRN 
Mutations and Diseases : HGMDWRN
Genomic VariantsWRN  WRN [DGVbeta]
dbVarWRN
ClinVarWRN
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM277700    604611   
MedgenWRN
OrphanetWerner syndrome
GENETestsWRN
Disease Genetic AssociationWRN
Huge Navigator WRN [HugePedia]  WRN [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneWRN
Homology/Alignments : Family Browser (UCSC)WRN
Phylogenetic Trees/Animal Genes : TreeFamWRN
Chemical/Protein Interactions : CTD7486
Chemical/Pharm GKB GenePA367
Clinical trialWRN
Cancer Resource (Charite)ENSG00000165392
Other databases
Other databasehttp://www.ncbi.nlm.nih.gov/cgi-bin/SCIENCE96/gene?WRN
Probes
Litterature
PubMed243 Pubmed reference(s) in Entrez
CoreMineWRN
iHOPWRN

Bibliography

Variegated translocation mosaicism in human skin fibroblast cultures.
Hoehn H, Bryant EM, Au K, Norwood TH, Boman H, Martin GM
Cytogenetics and cell genetics. 1975 ; 15 (5) : 282-298.
PMID 1222585
 
Mutator phenotype of Werner syndrome is characterized by extensive deletions.
Fukuchi K, Martin GM, Monnat RJ Jr
Proceedings of the National Academy of Sciences of the United States of America. 1989 ; 86 (15) : 5893-5897.
PMID 2762303
 
Increased frequency of 6-thioguanine-resistant peripheral blood lymphocytes in Werner syndrome patients.
Fukuchi K, Tanaka K, Kumahara Y, Marumo K, Pride MB, Martin GM, Monnat RJ Jr
Human genetics. 1990 ; 84 (3) : 249-252.
PMID 2303247
 
The gene responsible for Werner syndrome may be a cell division counting gene.
Faragher RG, Kill IR, Hunter JA, Pope FM, Tannock C, Shall S
Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 90 (24) : 12030-12034.
PMID 8265666
 
Werner syndrome and biological ageing: a molecular genetic hypothesis.
Thweatt R, Goldstein S
BioEssays : news and reviews in molecular, cellular and developmental biology. 1993 ; 15 (6) : 421-426.
PMID 8357345
 
Homozygous and compound heterozygous mutations at the Werner syndrome locus.
Oshima J, Yu CE, Piussan C, Klein G, Jabkowski J, Balci S, Miki T, Nakura J, Ogihara T, Ells J, Smith M, Melaragno MI, Fraccaro M, Scappaticci S, Matthews J, Ouais S, Jarzebowicz A, Schellenberg GD, Martin GM
Human molecular genetics. 1996 ; 5 (12) : 1909-1913.
PMID 8968742
 
Positional cloning of the Werner's syndrome gene.
Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, Matthews S, Nakura J, Miki T, Ouais S, Martin GM, Mulligan J, Schellenberg GD
Science (New York, N.Y.). 1996 ; 272 (5259) : 258-262.
PMID 8602509
 
An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants.
Ogburn CE, Oshima J, Poot M, Chen R, Hunt KE, Gollahon KA, Rabinovitch PS, Martin GM
Human genetics. 1997 ; 101 (2) : 121-125.
PMID 9402954
 
Nucleolar localization of the Werner syndrome protein in human cells.
Marciniak RA, Lombard DB, Johnson FB, Guarente L
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (12) : 6887-6892.
PMID 9618508
 
WRN mutations in Werner syndrome.
Moser MJ, Oshima J, Monnat RJ Jr
Human mutation. 1999 ; 13 (4) : 271-279.
PMID 10220139
 
Replication focus-forming activity 1 and the Werner syndrome gene product.
Yan H, Chen CY, Kobayashi R, Newport J
Nature genetics. 1998 ; 19 (4) : 375-378.
PMID 9697700
 
Physical and functional interaction between p53 and the Werner's syndrome protein.
Blander G, Kipnis J, Leal JF, Yu CE, Schellenberg GD, Oren M
The Journal of biological chemistry. 1999 ; 274 (41) : 29463-29469.
PMID 10506209
 
Functional interaction between the Werner Syndrome protein and DNA polymerase delta.
Kamath-Loeb AS, Johansson E, Burgers PM, Loeb LA
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (9) : 4603-4608.
PMID 10781066
 
Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts.
Wyllie FS, Jones CJ, Skinner JW, Haughton MF, Wallis C, Wynford-Thomas D, Faragher RG, Kipling D
Nature genetics. 2000 ; 24 (1) : 16-17.
PMID 10615119
 
Ku complex interacts with and stimulates the Werner protein.
Cooper MP, Machwe A, Orren DK, Brosh RM, Ramsden D, Bohr VA
Genes & development. 2000 ; 14 (8) : 907-912.
PMID 10783163
 
Functional interaction between Ku and the werner syndrome protein in DNA end processing.
Li B, Comai L
The Journal of biological chemistry. 2000 ; 275 (37) : 28349-28352.
PMID 10880505
 
The Werner syndrome protein contributes to induction of p53 by DNA damage.
Blander G, Zalle N, Leal JF, Bar-Or RL, Yu CE, Oren M
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000 ; 14 (14) : 2138-2140.
PMID 11023999
 
Werner protein recruits DNA polymerase delta to the nucleolus.
Szekely AM, Chen YH, Zhang C, Oshima J, Weissman SM
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (21) : 11365-11370.
PMID 11027336
 
Telomere repeat DNA forms a large non-covalent complex with unique cohesive properties which is dissociated by Werner syndrome DNA helicase in the presence of replication protein A.
Ohsugi I, Tokutake Y, Suzuki N, Ide T, Sugimoto M, Furuichi Y
Nucleic acids research. 2000 ; 28 (18) : 3642-3648.
PMID 10982887
 
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Contributor(s)

Written03-2001Mounira Amor-Guéret
Institut Curie - Section de Recherche, UMR 2027 CNRS, Bātiment 110, Centre Universitaire, F-91405 Orsay Cedex, France

Citation

This paper should be referenced as such :
Amor-Guéret, M
WRN (Werner syndrome, RecQ helicase-like)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):116-117.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/WRNID284.html

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indexed on : Fri Jul 11 17:07:36 CEST 2014

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