ID:WRN_HUMAN DESCRIPTION: RecName: Full=Werner syndrome ATP-dependent helicase; EC=3.6.4.12; AltName: Full=DNA helicase, RecQ-like type 3; Short=RecQ3; AltName: Full=Exonuclease WRN; EC=3.1.-.-; AltName: Full=RecQ protein-like 2; 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). CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. COFACTOR: Binds 2 magnesium ions per subunit. Has high activity with manganese and zinc ions (in vitro). SUBUNIT: 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. INTERACTION: P54132:BLM; NbExp=9; IntAct=EBI-368417, EBI-621372; P39748:FEN1; NbExp=10; IntAct=EBI-368417, EBI-707816; P09874:PARP1; NbExp=6; IntAct=EBI-368417, EBI-355676; P43351:RAD52; NbExp=9; IntAct=EBI-368417, EBI-706448; P27694:RPA1; NbExp=8; IntAct=EBI-368417, EBI-621389; Q96EB6:SIRT1; NbExp=9; IntAct=EBI-368417, EBI-1802965; Q15554:TERF2; NbExp=8; IntAct=EBI-368417, EBI-706637; P04637:TP53; NbExp=5; IntAct=EBI-368417, EBI-366083; P12956:XRCC6; NbExp=7; IntAct=EBI-368417, EBI-353208; SUBCELLULAR LOCATION: Nucleus, nucleolus. Nucleus. PTM: Phosphorylated by PRKDC. Phosphorylated upon DNA damage, probably by ATM or ATR. 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. DISEASE: Defects in WRN may be a cause of colorectal cancer (CRC) [MIM:114500]. SIMILARITY: Belongs to the helicase family. RecQ subfamily. SIMILARITY: Contains 1 3'-5' exonuclease domain. SIMILARITY: Contains 1 helicase ATP-binding domain. SIMILARITY: Contains 1 helicase C-terminal domain. SIMILARITY: Contains 1 HRDC domain. WEB RESOURCE: Name=WRN; Note=WRN mutation db (Warner disease); URL="http://www.pathology.washington.edu/werner/ws_wrn.html"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/WRNID284.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/WRN"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/wrn/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q14191
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AF091214 - Homo sapiens WRN (WRN) mRNA, complete cds. BC172837 - Synthetic construct Homo sapiens clone IMAGE:9094347 Werner syndrome protein (WRN) gene, partial cds. AB587570 - Synthetic construct DNA, clone: pF1KE1598, Homo sapiens WRN gene for Werner syndrome, RecQ helicase-like, without stop codon, in Flexi system. AY818673 - Homo sapiens Werner syndrome helicase mRNA, complete cds. JD194536 - Sequence 175560 from Patent EP1572962. JD166091 - Sequence 147115 from Patent EP1572962. JD407803 - Sequence 388827 from Patent EP1572962. JD479353 - Sequence 460377 from Patent EP1572962. JD300467 - Sequence 281491 from Patent EP1572962. BC172838 - Synthetic construct Homo sapiens clone IMAGE:9094348 Werner syndrome protein (WRN) gene, partial cds. BC172839 - Synthetic construct Homo sapiens clone IMAGE:9094349 Werner syndrome protein (WRN) gene, partial cds. AL833572 - Homo sapiens mRNA; cDNA DKFZp686C2056 (from clone DKFZp686C2056). BC172840 - Synthetic construct Homo sapiens clone IMAGE:9094350 Werner syndrome protein (WRN) gene, partial cds. AB209652 - Homo sapiens mRNA for Werner syndrome protein variant protein. JD503045 - Sequence 484069 from Patent EP1572962. JD507670 - Sequence 488694 from Patent EP1572962. JD305107 - Sequence 286131 from Patent EP1572962. JD490595 - Sequence 471619 from Patent EP1572962. JD092078 - Sequence 73102 from Patent EP1572962. JD151643 - Sequence 132667 from Patent EP1572962. JD556282 - Sequence 537306 from Patent EP1572962. JD522236 - Sequence 503260 from Patent EP1572962. JD558236 - Sequence 539260 from Patent EP1572962. JD564286 - Sequence 545310 from Patent EP1572962. JD558235 - Sequence 539259 from Patent EP1572962. JD082328 - Sequence 63352 from Patent EP1572962. JD286580 - Sequence 267604 from Patent EP1572962. JD554025 - Sequence 535049 from Patent EP1572962. JD502612 - Sequence 483636 from Patent EP1572962. JD511440 - Sequence 492464 from Patent EP1572962. JD516786 - Sequence 497810 from Patent EP1572962. JD083298 - Sequence 64322 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q14191 (Reactome details) participates in the following event(s):
R-HSA-4568846 CDKN2A (p14-ARF) SUMOylates WRN with SUMO1 R-HSA-5685985 EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment R-HSA-5686410 BLM mediates dissolution of double Holliday junction R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA R-HSA-5693589 D-loop dissociation and strand annealing R-HSA-5693542 Association of RPA complexes with ssDNA at resected DNA DSBs R-HSA-5685994 Long-range resection of DNA DSBs by EXO1 or DNA2 R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs R-HSA-5685156 ATR phosphorylates RPA2 R-HSA-5685341 BCDX2 complex stabilizes RAD51 filament R-HSA-5685838 CX3 complex binds D-loop structures R-HSA-5693620 D-loop formation mediated by PALB2, BRCA2 and RAD51 R-HSA-5684875 Binding of ATR:ATRIP to RPA at resected DNA DSBs R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends R-HSA-5693593 D-loop extension by DNA polymerases R-HSA-5693584 Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2) R-HSA-5686440 MUS81:EME1,EME2 cleaves D-loop R-HSA-5685011 ATR activation at DNA DSBs R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs R-HSA-6799332 ATR phosphorylates TP53 R-HSA-3108214 SUMOylation of DNA damage response and repair proteins R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) R-HSA-2990846 SUMOylation R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693537 Resolution of D-Loop Structures R-HSA-597592 Post-translational protein modification R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-5693538 Homology Directed Repair R-HSA-392499 Metabolism of proteins R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-73894 DNA Repair R-HSA-69473 G2/M DNA damage checkpoint R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-69481 G2/M Checkpoints R-HSA-5633007 Regulation of TP53 Activity R-HSA-69620 Cell Cycle Checkpoints R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-1640170 Cell Cycle R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
