WRN WRN RecQ like helicase [Homo sapiens (human)] - Gene

Summary

Official Symbol: WRNprovided by HGNC
Official Full Name: WRN RecQ like helicaseprovided by HGNC
Primary source: HGNC:HGNC:12791
See related: Ensembl:ENSG00000165392 MIM:604611
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RECQ3; RECQL2; RECQL3
Summary: This gene encodes a member of the RecQ subfamily of DNA helicase proteins. The encoded nuclear protein is important in the maintenance of genome stability and plays a role in DNA repair, replication, transcription and telomere maintenance. This protein contains a N-terminal 3' to 5' exonuclease domain, an ATP-dependent helicase domain and RQC (RecQ helicase conserved region) domain in its central region, and a C-terminal HRDC (helicase RNase D C-terminal) domain and nuclear localization signal. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by accelerated aging and an elevated risk for certain cancers. [provided by RefSeq, Aug 2017]
Expression: Ubiquitous expression in bone marrow (RPKM 5.0), endometrium (RPKM 4.7) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 8p12

Exon count:: 38

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	8	NC_000008.11 (31033749..31176138)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (30890778..31031277)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Both K1127 and K1117 is essential for the recruitment of this protein at DNA damage site and for successful DNA repair.
Title: Acetylation of Werner protein at K1127 and K1117 is important for nuclear trafficking and DNA repair.
WRN was selectively essential in microsatellite instability models in vitro and in vivo, yet dispensable in models of cancers that are microsatellite stable; WRN depletion induced double-stranded DNA breaks and promoted apoptosis and cell cycle arrest selectively in MSI models; MSI cancer models required the helicase activity of WRN, but not its exonuclease activity
Title: WRN helicase is a synthetic lethal target in microsatellite unstable cancers.
HERC2 is a master regulator of G-quadruplex, a DNA secondary structure that triggers genomic instability, through BLM, WRN, and RPA, and may serve as a potential molecular target in cancer therapy
Title: HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G-Quadruplex DNA.
these findings suggest a potential role of WRN as regulator of R-loop-associated genomic instability, strengthening the notion that conflicts between replication and transcription can affect DNA replication, leading to human disease and cancer.
Title: ATM pathway activation limits R-loop-associated genomic instability in Werner syndrome cells.
Summary of studies shows mutation C1367R in WRN increases risk of myocardial infarction in Japanese populations, ischemic stroke and breast cancer in European populations, bipolar disorder in multi-ethnic populations; WRN L1074F increases breast cancer risk in Asian populations with early menarche; WRN V114I confers worst effect on refractive error of the eye, and bone fracture in Japanese populations
Title: Werner syndrome (WRN) gene variants and their association with altered function and age-associated diseases.
study found that six cases of gastric cancers (GCs) and colorectal cancers (CRCs) with MSI-H harbored WRN frameshift mutations, indicating that WRN is mutated in some GCs and CRCs with MSI-H
Title: WRN, the Werner Syndrome Gene, Exhibits Frameshift Mutations in Gastric and Colorectal Cancers.
WRN's activity is differently modulated by replication protein A (RPA) in a concentration dependent manner, and that full stimulation of the helicase activity of WRN requires the binding of multiple RPAs.
Title: Multiple RPAs make WRN syndrome protein a superhelicase.
Here, the authors demonstrate that SIRT1 promotes the fidelity of human papillomavirus type 16 E1-E2 replication and that the absence of SIRT1 results in reduced recruitment of the DNA repair protein Werner helicase (WRN) to E1-E2-replicating DNA.
Title: Werner Helicase Control of Human Papillomavirus 16 E1-E2 DNA Replication Is Regulated by SIRT1 Deacetylation.
MDM2 is critically involved in regulating WRN function via ubiquitin-dependent degradation and reveal an unexpected role of MDM2 in promoting cellular senescence through a p53-independent manner.
Title: MDM2-mediated degradation of WRN promotes cellular senescence in a p53-independent manner.
An in vitro transcription assay demonstrated that the c.3139-1G>C allele led to skipping of exon 26. The mutation c.2485_2486delAA has never been reported before. We confirmed c.2485_2486delAA to be absent in the Exome Aggregation Consortium and the Human Genetic Variation Database.
Title: A novel WRN mutation identified in a patient with Werner syndrome and acute generalized exanthematous pustulosis.

Submit: New GeneRIF Correction See all GeneRIFs (225)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Werner syndrome MedGen: C0043119 OMIM: 277700 GeneReviews: Werner Syndrome	Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Werner syndrome helicase co-localizes with Tat in central nervous system tissue (thalamus and basal ganglia)	PubMed
	tat	Werner syndrome helicase cooperates with HIV-1 Tat to transactivate the HIV-1 LTR. The helicase K577M mutant inhibits Tat-dependent LTR transactivation in a dose-dependent manner	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH64913 (e-PCR)
- UniSTS:86304

PMC109206P1 (e-PCR)
- UniSTS:270155

WI-17945 (e-PCR)
- UniSTS:23392

SHGC-111489 (e-PCR)
- UniSTS:184679

SHGC-106496 (e-PCR)
- UniSTS:169897

D8S2234 (e-PCR)
- UniSTS:473787

D8S2233 (e-PCR)
- UniSTS:473788

csnpwrn-pcr13-1 (e-PCR)
- UniSTS:243166

csnpwrn-pcr14-1 (e-PCR)
- UniSTS:243167

csnpwrn-pcr15-1 (e-PCR)
- UniSTS:243168

csnpwrn-pcr18-1 (e-PCR)
- UniSTS:243169

csnpwrn-pcr2-1 (e-PCR)
- UniSTS:243170

csnpwrn-pcr20-1 (e-PCR)
- UniSTS:243171

csnpwrn-pcr21-1 (e-PCR)
- UniSTS:243172

csnpwrn-pcr22-1 (e-PCR)
- UniSTS:243173

csnpwrn-pcr23-1 (e-PCR)
- UniSTS:243174

csnpwrn-pcr25-1 (e-PCR)
- UniSTS:243175

csnpwrn-pcr26-1 (e-PCR)
- UniSTS:243176

csnpwrn-pcr27-1 (e-PCR)
- UniSTS:243177

csnpwrn-pcr29-1 (e-PCR)
- UniSTS:243178

csnpwrn-pcr30-1 (e-PCR)
- UniSTS:243179

csnpwrn-pcr31-1 (e-PCR)
- UniSTS:243180

csnpwrn-pcr34-1 (e-PCR)
- UniSTS:243181

csnpwrn-pcr4-1 (e-PCR)
- UniSTS:243182

PMC117198P1 (e-PCR)
- UniSTS:270319

csnpwrn-pcr5-1 (e-PCR)
- UniSTS:243183

csnpwrn-pcr6-1 (e-PCR)
- UniSTS:243184

csnpwrn-pcr7-1 (e-PCR)
- UniSTS:243185

G63421 (e-PCR)
- UniSTS:140533

SHGC-37564 (e-PCR)
- UniSTS:77823

Homology

Homologs of the WRN gene: The WRN gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, C.elegans, rice, and frog.
Orthologs from Annotation Pipeline: 267 organisms have orthologs with human gene WRN
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
3'-5' DNA helicase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
3'-5' DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
3'-5' exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
3'-flap-structured DNA binding	IDA Inferred from Direct Assay more info	PubMed
8-hydroxy-2'-deoxyguanosine DNA binding	IDA Inferred from Direct Assay more info	PubMed
ATP binding	IEA Inferred from Electronic Annotation more info
ATPase activity	IDA Inferred from Direct Assay more info	PubMed
DNA binding	IDA Inferred from Direct Assay more info	PubMed
DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
DNA helicase activity	IMP Inferred from Mutant Phenotype more info	PubMed
G-quadruplex DNA binding	IDA Inferred from Direct Assay more info	PubMed
MutLalpha complex binding	IDA Inferred from Direct Assay more info	PubMed
Y-form DNA binding	IDA Inferred from Direct Assay more info	PubMed
bubble DNA binding	IDA Inferred from Direct Assay more info	PubMed
chromatin binding	IEA Inferred from Electronic Annotation more info
exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
exonuclease activity	IMP Inferred from Mutant Phenotype more info	PubMed
forked DNA-dependent helicase activity	IDA Inferred from Direct Assay more info	PubMed
four-way junction DNA binding	IDA Inferred from Direct Assay more info	PubMed
four-way junction helicase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
four-way junction helicase activity	IDA Inferred from Direct Assay more info	PubMed
helicase activity	IDA Inferred from Direct Assay more info	PubMed
magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
manganese ion binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
telomeric D-loop binding	IDA Inferred from Direct Assay more info	PubMed
telomeric G-quadruplex DNA binding	IC Inferred by Curator more info	PubMed

Process	Evidence Code	Pubs
DNA duplex unwinding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA duplex unwinding	IDA Inferred from Direct Assay more info	PubMed
DNA metabolic process	IDA Inferred from Direct Assay more info	PubMed
DNA recombination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA repair	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
DNA replication	ISS Inferred from Sequence or Structural Similarity more info
DNA replication	TAS Traceable Author Statement more info
DNA synthesis involved in DNA repair	IDA Inferred from Direct Assay more info	PubMed
DNA unwinding involved in DNA replication	IBA Inferred from Biological aspect of Ancestor more info	PubMed
G-quadruplex DNA unwinding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
G-quadruplex DNA unwinding	IDA Inferred from Direct Assay more info	PubMed
G-quadruplex DNA unwinding	ISS Inferred from Sequence or Structural Similarity more info
aging	NAS Non-traceable Author Statement more info	PubMed
base-excision repair	IDA Inferred from Direct Assay more info	PubMed
brain development	IEA Inferred from Electronic Annotation more info
cell aging	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to DNA damage stimulus	IDA Inferred from Direct Assay more info	PubMed
cellular response to gamma radiation	IDA Inferred from Direct Assay more info	PubMed
cellular response to starvation	IDA Inferred from Direct Assay more info	PubMed
double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
double-strand break repair via homologous recombination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
multicellular organism aging	IBA Inferred from Biological aspect of Ancestor more info	PubMed
multicellular organism aging	IMP Inferred from Mutant Phenotype more info	PubMed
nucleic acid phosphodiester bond hydrolysis	IEA Inferred from Electronic Annotation more info
positive regulation of hydrolase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of strand invasion	IDA Inferred from Direct Assay more info	PubMed
protein localization to nucleolus	IDA Inferred from Direct Assay more info	PubMed
regulation of apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
regulation of growth rate	IEA Inferred from Electronic Annotation more info
regulation of signal transduction by p53 class mediator	TAS Traceable Author Statement more info
replication fork processing	IDA Inferred from Direct Assay more info	PubMed
replication fork processing	IMP Inferred from Mutant Phenotype more info	PubMed
replicative cell aging	IEA Inferred from Electronic Annotation more info
response to UV-C	IDA Inferred from Direct Assay more info	PubMed
response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
t-circle formation	TAS Traceable Author Statement more info	PubMed
telomere maintenance	IBA Inferred from Biological aspect of Ancestor more info	PubMed
telomere maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
telomere maintenance	TAS Traceable Author Statement more info	PubMed
telomeric D-loop disassembly	IDA Inferred from Direct Assay more info	PubMed
telomeric D-loop disassembly	IGI Inferred from Genetic Interaction more info	PubMed
telomeric D-loop disassembly	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
centrosome	IDA Inferred from Direct Assay more info	PubMed
chromosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed
chromosome, telomeric region	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
neuron projection	IEA Inferred from Electronic Annotation more info
nuclear speck	IDA Inferred from Direct Assay more info
nucleolus	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
replication fork	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: Werner syndrome ATP-dependent helicase

Names: DNA helicase, RecQ-like type 3; Werner syndrome RecQ like helicase; Werner syndrome, RecQ helicase-like; exonuclease WRN; recQ protein-like 2

NP_000544.2

EC 3.6.4.12

XP_011542941.1

EC 3.6.4.12

XP_011542942.1

EC 3.6.4.12

XP_024303033.1

EC 3.6.4.12

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008870.1 RefSeqGene

Range

5001..145500

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_524

mRNA and Protein(s)

NM_000553.6 → NP_000544.2 Werner syndrome ATP-dependent helicase

See identical proteins and their annotated locations for NP_000544.2

Status: REVIEWED

Source sequence(s)

AC009563, AC084736

Consensus CDS

CCDS6082.1

UniProtKB/Swiss-Prot

Q14191

Related

ENSP00000298139.5, ENST00000298139.7

Conserved Domains (8) summary

smart00341
Location:1156 → 1229

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:538 → 1010

recQ_fam; ATP-dependent DNA helicase, RecQ family

cd06129
Location:61 → 229

RNaseD_like; DEDDy 3'-5' exonuclease domain of RNase D, WRN, and similar proteins

smart00956
Location:958 → 1051

RQC; This DNA-binding domain is found in the RecQ helicase among others and has a helix-turn-helix structure

cd00079
Location:759 → 867

HELICc; Helicase superfamily c-terminal domain; associated with DEXDc-, DEAD-, and DEAH-box proteins, yeast initiation factor 4A, Ski2p, and Hepatitis C virus NS3 helicases; this domain is found in a wide variety of helicases and helicase related proteins; may ...

pfam00270
Location:551 → 712

DEAD; DEAD/DEAH box helicase

pfam14493
Location:1261 → 1351

HTH_40; Helix-turn-helix domain

pfam16124
Location:872 → 939

RecQ_Zn_bind; RecQ zinc-binding

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p13 Primary Assembly

Range

31033749..31176138

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011544639.3 → XP_011542941.1 Werner syndrome ATP-dependent helicase isoform X1

See identical proteins and their annotated locations for XP_011542941.1

Conserved Domains (8) summary

smart00341
Location:1129 → 1202

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:511 → 983

recQ_fam; ATP-dependent DNA helicase, RecQ family

cd06129
Location:61 → 229

RNaseD_like; DEDDy 3'-5' exonuclease domain of RNase D, WRN, and similar proteins

smart00956
Location:931 → 1024

RQC; This DNA-binding domain is found in the RecQ helicase among others and has a helix-turn-helix structure

cd00079
Location:732 → 840

HELICc; Helicase superfamily c-terminal domain; associated with DEXDc-, DEAD-, and DEAH-box proteins, yeast initiation factor 4A, Ski2p, and Hepatitis C virus NS3 helicases; this domain is found in a wide variety of helicases and helicase related proteins; may ...

pfam00270
Location:524 → 685

DEAD; DEAD/DEAH box helicase

pfam14493
Location:1234 → 1324

HTH_40; Helix-turn-helix domain

pfam16124
Location:845 → 912

RecQ_Zn_bind; RecQ zinc-binding
XM_024447265.1 → XP_024303033.1 Werner syndrome ATP-dependent helicase isoform X2

Conserved Domains (5) summary

smart00341
Location:1086 → 1159

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:468 → 940

recQ_fam; ATP-dependent DNA helicase, RecQ family

cd06129
Location:4 → 159

RNaseD_like; DEDDy 3'-5' exonuclease domain of RNase D, WRN, and similar proteins

pfam14493
Location:1188 → 1282

HTH_40; Helix-turn-helix domain

cl28246
Location:86 → 410

DnaJ; DnaJ-class molecular chaperone with C-terminal Zn finger domain [Posttranslational modification, protein turnover, chaperones]
XM_011544640.1 → XP_011542942.1 Werner syndrome ATP-dependent helicase isoform X3

Related

ENST00000521620.5

Conserved Domains (7) summary

smart00341
Location:623 → 696

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:42 → 477

recQ_fam; ATP-dependent DNA helicase, RecQ family

smart00956
Location:425 → 518

RQC; This DNA-binding domain is found in the RecQ helicase among others and has a helix-turn-helix structure

cd00079
Location:226 → 334

HELICc; Helicase superfamily c-terminal domain; associated with DEXDc-, DEAD-, and DEAH-box proteins, yeast initiation factor 4A, Ski2p, and Hepatitis C virus NS3 helicases; this domain is found in a wide variety of helicases and helicase related proteins; may ...

pfam00270
Location:42 → 179

DEAD; DEAD/DEAH box helicase

pfam14493
Location:728 → 818

HTH_40; Helix-turn-helix domain

pfam16124
Location:339 → 406

RecQ_Zn_bind; RecQ zinc-binding