Wrn Werner syndrome RecQ like helicase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Wrnprovided by MGI
Official Full Name: Werner syndrome RecQ like helicaseprovided by MGI
Primary source: MGI:MGI:109635
See related: Ensembl:ENSMUSG00000031583 AllianceGenome:MGI:109635
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary: Enables 3'-5' exonuclease activity. Involved in DNA replication and G-quadruplex DNA unwinding. Acts upstream of or within several processes, including determination of adult lifespan; regulation of growth rate; and replicative senescence. Located in chromosome, telomeric region; nucleoplasm; and replication fork. Is expressed in coelomic epithelium of testis; metanephros; and spleen. Used to study Werner syndrome. Human ortholog(s) of this gene implicated in Werner syndrome; breast cancer; coronary artery disease (multiple); diffuse scleroderma; and senile cataract. Orthologous to human WRN (WRN RecQ like helicase). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in liver E14 (RPKM 4.4), liver E14.5 (RPKM 3.9) and 25 other tissues See more
Orthologs: human all
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Genomic context

Location:: 8 A3; 8 20.3 cM

Exon count:: 35

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (33724400..33875591, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (33234372..33385543, complement)

Chromosome 8 - NC_000074.7 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: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells.
Title: WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells.
These results suggest that a great number of endoplasmic reticulum (ER) gene products are regulated at the post-transcriptional level in the liver of Wrn mutant mice exhibiting an ER stress response.
Title: Vitamin C alters the amount of specific endoplasmic reticulum associated proteins involved in lipid metabolism in the liver of mice synthesizing a nonfunctional Werner syndrome (Wrn) mutant protein.
A mislocalization of the Wrn mutant protein in the liver endoplasmic reticulum fraction increased oxidative stress in that cellular compartment. Vitamin C reversed this oxidative stress.
Title: Impact of vitamin C on the cardiometabolic and inflammatory profiles of mice lacking a functional Werner syndrome protein helicase.
The deleterious effects of the helicase-deficient Wrn protein are mediated by the dysfunction of several cellular organelles.
Title: Metabolic and Phenotypic Differences between Mice Producing a Werner Syndrome Helicase Mutant Protein and Wrn Null Mice.
Data suggest that, in the context of Wrn deficiency-related telomere dysfunction, loss of p16Ink4a function could prevent cells from senescence.
Title: Loss of p16(Ink4a) function rescues cellular senescence induced by telomere dysfunction.
The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers.
Title: The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers.
Studies show that in the context of Myc-associated tumorigenesis, loss of Wrn amplifies the DNA damage response, both in preneoplastic and neoplastic tissue, engaging activation of tumor suppressor pathways.
Title: MYC-driven tumorigenesis is inhibited by WRN syndrome gene deficiency.
embryonic fibroblasts lacking a functional Wrn helicase inhibited the immortalization of Safb1-null cells. These results indicate that an intact Wrn protein is required for immortalization and tumorigenesis in Safb1-null mice.
Title: The Werner syndrome helicase protein is required for cell proliferation, immortalization, and tumorigenesis in Scaffold attachment factor B1 deficient mice.
BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability.
Title: BCR/ABL stimulates WRN to promote survival and genomic instability.
WRN has a role in processing specific types of homologous recombination intermediates as well as an important function in nonhomologous recombination
Title: Depletion of Werner helicase results in mitotic hyperrecombination and pleiotropic homologous and nonhomologous recombination phenotypes.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1)
Endonuclease-mediated (6)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D86526 (e-PCR)
- UniSTS:179725

NoName (e-PCR)
- UniSTS:235864

Wrn (e-PCR), detects polymorphism
- UniSTS:259699

NoName (e-PCR)
- UniSTS:481162

PMC23722P1 (e-PCR)
- UniSTS:144787

D1S3698 (e-PCR)
- UniSTS:474276

AI846146 (e-PCR)
- UniSTS:165574

UniSTS:488917 (e-PCR)
- UniSTS:488917

PMC117198P1 (e-PCR)
- UniSTS:270319

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables 3'-5' DNA helicase activity	IBA Inferred from Biological aspect of Ancestor more info
enables 3'-5' DNA helicase activity	IEA Inferred from Electronic Annotation more info
enables 3'-5' DNA helicase activity	ISO Inferred from Sequence Orthology more info
enables 3'-5' exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables 3'-5' exonuclease activity	ISO Inferred from Sequence Orthology more info
enables 3'-5' exonuclease activity	ISS Inferred from Sequence or Structural Similarity more info
enables 3'-flap-structured DNA binding	IEA Inferred from Electronic Annotation more info
enables 3'-flap-structured DNA binding	ISO Inferred from Sequence Orthology more info
enables 8-hydroxy-2'-deoxyguanosine DNA binding	IEA Inferred from Electronic Annotation more info
enables 8-hydroxy-2'-deoxyguanosine DNA binding	ISO Inferred from Sequence Orthology more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	ISO Inferred from Sequence Orthology more info
enables DNA binding	ISO Inferred from Sequence Orthology more info
enables DNA helicase activity	ISO Inferred from Sequence Orthology more info
enables G-quadruplex DNA binding	ISO Inferred from Sequence Orthology more info
enables MutLalpha complex binding	IEA Inferred from Electronic Annotation more info
enables MutLalpha complex binding	ISO Inferred from Sequence Orthology more info
enables Y-form DNA binding	IEA Inferred from Electronic Annotation more info
enables Y-form DNA binding	ISO Inferred from Sequence Orthology more info
enables bubble DNA binding	IEA Inferred from Electronic Annotation more info
enables bubble DNA binding	ISO Inferred from Sequence Orthology more info
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables chromatin binding	ISO Inferred from Sequence Orthology more info
enables exonuclease activity	ISO Inferred from Sequence Orthology more info
enables forked DNA-dependent helicase activity	IEA Inferred from Electronic Annotation more info
enables forked DNA-dependent helicase activity	ISO Inferred from Sequence Orthology more info
enables four-way junction DNA binding	IEA Inferred from Electronic Annotation more info
enables four-way junction DNA binding	ISO Inferred from Sequence Orthology more info
enables four-way junction helicase activity	IBA Inferred from Biological aspect of Ancestor more info
enables four-way junction helicase activity	IEA Inferred from Electronic Annotation more info
enables four-way junction helicase activity	ISO Inferred from Sequence Orthology more info
enables isomerase activity	IEA Inferred from Electronic Annotation more info
enables magnesium ion binding	ISO Inferred from Sequence Orthology more info
enables magnesium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables manganese ion binding	ISO Inferred from Sequence Orthology more info
enables manganese ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables telomeric D-loop binding	IEA Inferred from Electronic Annotation more info
enables telomeric D-loop binding	ISO Inferred from Sequence Orthology more info
enables telomeric G-quadruplex DNA binding	IEA Inferred from Electronic Annotation more info
enables telomeric G-quadruplex DNA binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in DNA damage response	ISO Inferred from Sequence Orthology more info
involved_in DNA duplex unwinding	IEA Inferred from Electronic Annotation more info
involved_in DNA duplex unwinding	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within DNA metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA metabolic process	ISO Inferred from Sequence Orthology more info
involved_in DNA metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in DNA recombination	IEA Inferred from Electronic Annotation more info
involved_in DNA replication	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA replication	ISO Inferred from Sequence Orthology more info
involved_in DNA synthesis involved in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in DNA synthesis involved in DNA repair	ISO Inferred from Sequence Orthology more info
involved_in DNA unwinding involved in DNA replication	IBA Inferred from Biological aspect of Ancestor more info
involved_in G-quadruplex DNA unwinding	IBA Inferred from Biological aspect of Ancestor more info
involved_in G-quadruplex DNA unwinding	IGI Inferred from Genetic Interaction more info	PubMed
involved_in G-quadruplex DNA unwinding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in G-quadruplex DNA unwinding	ISO Inferred from Sequence Orthology more info
involved_in base-excision repair	IEA Inferred from Electronic Annotation more info
involved_in base-excision repair	ISO Inferred from Sequence Orthology more info
involved_in cellular response to gamma radiation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to gamma radiation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within cellular response to starvation	ISO Inferred from Sequence Orthology more info	PubMed
involved_in cellular senescence	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within determination of adult lifespan	IGI Inferred from Genetic Interaction more info	PubMed
involved_in double-strand break repair	ISO Inferred from Sequence Orthology more info
involved_in double-strand break repair	ISS Inferred from Sequence or Structural Similarity more info
involved_in double-strand break repair via homologous recombination	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of hydrolase activity	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of hydrolase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of strand invasion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of strand invasion	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein localization to nucleolus	ISO Inferred from Sequence Orthology more info	PubMed
acts_upstream_of_or_within regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of growth rate	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in replication fork processing	IEA Inferred from Electronic Annotation more info
involved_in replication fork processing	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within replicative senescence	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to UV-C	IEA Inferred from Electronic Annotation more info
involved_in response to UV-C	ISO Inferred from Sequence Orthology more info
involved_in response to oxidative stress	IEA Inferred from Electronic Annotation more info
involved_in response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in telomere maintenance	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within telomere maintenance	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within telomere maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in telomere maintenance	ISO Inferred from Sequence Orthology more info
involved_in telomeric D-loop disassembly	IEA Inferred from Electronic Annotation more info
involved_in telomeric D-loop disassembly	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in centrosome	IEA Inferred from Electronic Annotation more info
located_in centrosome	ISO Inferred from Sequence Orthology more info
is_active_in chromosome	IBA Inferred from Biological aspect of Ancestor more info
located_in chromosome, telomeric region	IMP Inferred from Mutant Phenotype more info	PubMed
located_in chromosome, telomeric region	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in nuclear speck	IEA Inferred from Electronic Annotation more info
located_in nuclear speck	ISO Inferred from Sequence Orthology more info
NOT located_in nucleolus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleolus	ISO Inferred from Sequence Orthology more info	PubMed
located_in nucleolus	ISS Inferred from Sequence or Structural Similarity more info
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in replication fork	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN

Names: Werner syndrome ATP-dependent helicase homolog; Werner syndrome homolog; Werner syndrome protein homolog; exonuclease WRN

NP_001116294.1

EC 5.6.2.4

NP_035851.3

EC 5.6.2.4

XP_006509154.1

EC 5.6.2.4

XP_006509156.1

EC 5.6.2.4

XP_017168151.1

EC 5.6.2.4

XP_036009773.1

EC 5.6.2.4

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.

mRNA and Protein(s)

NM_001122822.1 → NP_001116294.1 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN

See identical proteins and their annotated locations for NP_001116294.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 both encode the same protein.

Source sequence(s)

AK052466, AK162801, AK171490, BC050921

Consensus CDS

CCDS22229.1

UniProtKB/Swiss-Prot

O09050, O09053, Q80YP9, Q9JKD4, Q9Z241, Q9Z242

UniProtKB/TrEMBL

A0A1B0GR54

Related

ENSMUSP00000033991.7, ENSMUST00000033991.13

Conserved Domains (5) summary

smart00341
Location:1116 → 1194

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:502 → 975

recQ_fam; ATP-dependent DNA helicase, RecQ family

TIGR01388
Location:156 → 344

rnd; ribonuclease D

cd06129
Location:55 → 223

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

pfam14493
Location:1223 → 1317

HTH_40; Helix-turn-helix domain
NM_011721.4 → NP_035851.3 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN

See identical proteins and their annotated locations for NP_035851.3

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 both encode the same protein.

Source sequence(s)

AK052466, AK162801, AK171490, BC050921

Consensus CDS

CCDS22229.1

UniProtKB/Swiss-Prot

O09050, O09053, Q80YP9, Q9JKD4, Q9Z241, Q9Z242

UniProtKB/TrEMBL

A0A1B0GR54

Related

ENSMUSP00000033990.6, ENSMUST00000033990.7

Conserved Domains (5) summary

smart00341
Location:1116 → 1194

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:502 → 975

recQ_fam; ATP-dependent DNA helicase, RecQ family

TIGR01388
Location:156 → 344

rnd; ribonuclease D

cd06129
Location:55 → 223

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

pfam14493
Location:1223 → 1317

HTH_40; Helix-turn-helix domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000074.7 Reference GRCm39 C57BL/6J

Range

33724400..33875591 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006509093.5 → XP_006509156.1 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN isoform X2

UniProtKB/TrEMBL

A0A1B0GR54

Conserved Domains (4) summary

smart00341
Location:1115 → 1193

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:501 → 974

recQ_fam; ATP-dependent DNA helicase, RecQ family

cd06129
Location:55 → 223

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

pfam14493
Location:1222 → 1316

HTH_40; Helix-turn-helix domain
XM_006509091.5 → XP_006509154.1 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN isoform X1

See identical proteins and their annotated locations for XP_006509154.1

UniProtKB/Swiss-Prot

O09050, O09053, Q80YP9, Q9JKD4, Q9Z241, Q9Z242

UniProtKB/TrEMBL

A0A1B0GR54

Conserved Domains (5) summary

smart00341
Location:1116 → 1194

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:502 → 975

recQ_fam; ATP-dependent DNA helicase, RecQ family

TIGR01388
Location:156 → 344

rnd; ribonuclease D

cd06129
Location:55 → 223

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

pfam14493
Location:1223 → 1317

HTH_40; Helix-turn-helix domain
XM_036153880.1 → XP_036009773.1 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN isoform X2

UniProtKB/TrEMBL

A0A1B0GR54

Conserved Domains (4) summary

smart00341
Location:1115 → 1193

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:501 → 974

recQ_fam; ATP-dependent DNA helicase, RecQ family

cd06129
Location:55 → 223

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

pfam14493
Location:1222 → 1316

HTH_40; Helix-turn-helix domain
XM_017312662.3 → XP_017168151.1 bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN isoform X1

UniProtKB/Swiss-Prot

O09050, O09053, Q80YP9, Q9JKD4, Q9Z241, Q9Z242

UniProtKB/TrEMBL

A0A1B0GR54

Conserved Domains (5) summary

smart00341
Location:1116 → 1194

HRDC; Helicase and RNase D C-terminal

TIGR00614
Location:502 → 975

recQ_fam; ATP-dependent DNA helicase, RecQ family

TIGR01388
Location:156 → 344

rnd; ribonuclease D

cd06129
Location:55 → 223

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

pfam14493
Location:1223 → 1317

HTH_40; Helix-turn-helix domain