Tbio WRN Werner syndrome ATP-dependent helicase

Protein Summary

Description

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). Plays a role in double-strand break repair after gamma-irradiation. 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]

Uniprot Accession IDs

• Q14191
• A1KYY9

Gene Name

• WRN

Ensembl ID

• ENST00000298139
• ENSP00000298139
• ENSG00000165392

Symbol

• RECQ3
• RECQL2
• RECQ3
• RECQL2
• RECQL3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
protein domain	1
biological process	0.78
cellular component	0.74
disease perturbation	0.74

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Helicase / Dna Helicase / Werner Syndrome Atp-dependent Helicase

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna Helicase / Werner Syndrome Atp-dependent Helicase

DTO Classes

Protein / Enzyme / Helicase / Dna Helicase / Werner Syndrome Atp-dependent Helicase

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 711.48   (req: < 5)

Gene RIFs: 218   (req: <= 3)

Antibodies: 275   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 711.48   (req: >= 5)

Gene RIFs: 218   (req: > 3)

Antibodies: 275   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 56

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (311)

Explore Interacting Targets

1 – 10 of 311

• See Interactions on String-DB

XRCC6

Tbio

Novelty:  0.00127955

p_int:  0.999999985

p_ni:  1.2e-8

p_wrong:  3e-9

Score:  0.994

Data Source:  BioPlex,STRINGDB

PDP1

Tbio

Family:  Enzyme

Novelty:  0.00442352

p_int:  0.999955552

p_ni:  0.000044418

p_wrong:  3e-8

Data Source:  BioPlex

SKAP1

Tbio

Family:  Enzyme

Novelty:  0.03753848

p_int:  0.982684747

p_ni:  0.017315165

p_wrong:  8.8e-8

Score:  0.173

Data Source:  BioPlex,STRINGDB

KIAA0930

Tbio

Novelty:  0.16492958

p_int:  0.946382606

p_ni:  0.0514778

p_wrong:  0.002139594

Score:  0.219

Data Source:  BioPlex,STRINGDB

RPA1

Tchem

Novelty:  0.00212665

Score:  0.999

Data Source:  Reactome,STRINGDB

RPA2

Tbio

Novelty:  0.00879115

Score:  0.999

Data Source:  Reactome,STRINGDB

RPA3

Tbio

Novelty:  0.00887858

Score:  0.999

Data Source:  Reactome,STRINGDB

EXO1

Tbio

Family:  Enzyme

Novelty:  0.00130104

Score:  0.996

Data Source:  STRINGDB

ATM

Tchem

Family:  Kinase

Novelty:  0.00019169

Score:  0.995

Data Source:  Reactome,STRINGDB

RAD52

Tchem

Novelty:  0.00125282

Score:  0.994

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (30)

Reactome (27)

PathwayCommons (2)

WikiPathways (1)

Cell Cycle (R-HSA-1640170)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cell Cycle	597 targets	R-HSA-1640170
Reactome	Cell Cycle Checkpoints	272 targets	R-HSA-69620
Reactome	DNA Double-Strand Break Repair	146 targets	R-HSA-5693532
Reactome	DNA Repair	306 targets	R-HSA-73894
Reactome	G2/M Checkpoints	150 targets	R-HSA-69481

Name	Explore in Pharos	Explore in Source
Cell Cycle	597 targets	R-HSA-1640170
Cell Cycle Checkpoints	272 targets	R-HSA-69620
DNA Double-Strand Break Repair	146 targets	R-HSA-5693532
DNA Repair	306 targets	R-HSA-73894
G2/M Checkpoints	150 targets	R-HSA-69481

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (67)

Functions (26)

Components (11)

Processes (30)

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10

1 – 10 of 26

GO Term	Evidence	Assigned by
3'-5' DNA helicase activity	Inferred from Direct Assay (IDA)	UniProtKB
3'-5' exonuclease activity	Inferred from Direct Assay (IDA)	UniProtKB
3'-flap-structured DNA binding	Inferred from Direct Assay (IDA)	BHF-UCL
8-hydroxy-2'-deoxyguanosine DNA binding	Inferred from Direct Assay (IDA)	BHF-UCL
ATP-dependent DNA helicase activity	Inferred from Direct Assay (IDA)	UniProtKB
ATPase activity	Inferred from Direct Assay (IDA)	UniProtKB
bubble DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA helicase activity	Inferred from Direct Assay (IDA)	BHF-UCL
exonuclease activity	Inferred from Direct Assay (IDA)	MGI

Disease Associations ()

No disease associations found

GWAS Traits (15)

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1 – 5 of 15

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	4	3	4		91.5
self reported educational attainment	EFO_0004784	2	3	3		89.8
cognitive function measurement	EFO_0008354	3	2	4		78.2
type II diabetes mellitus	EFO_0001360	4	4	3	1	75.7
body mass index	EFO_0004340	2	2	2		72.1

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	4		91.5
self reported educational attainment	EFO_0004784	3		89.8
cognitive function measurement	EFO_0008354	4		78.2
type II diabetes mellitus	EFO_0001360	3	1	75.7
body mass index	EFO_0004340	2		72.1

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UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
ATP-binding
Complete proteome
Direct protein sequencing
Disease mutation
DNA damage
DNA repair
DNA-binding
Exonuclease

GWAS Trait Find Similar Targets

No Header	No Header
body height
body mass index
cognitive function measurement
Diuretic use measurement
household income
insomnia measurement
intelligence
longevity
mathematical ability
metabolic syndrome

MGI Phenotype Find Similar Targets

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adipose tissue phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	Werner syndrome RecQ like helicase	VGNC:7604	472732
Macaque	Werner syndrome RecQ like helicase		695678
Mouse	Werner syndrome RecQ like helicase	MGI:109635	22427
Rat	Werner syndrome RecQ like helicase	RGD:1564788	290805
Dog	Werner syndrome RecQ like helicase		493997

Species	Name	OMA	EggNOG	Inparanoid
Chimp	Werner syndrome RecQ like helicase
Macaque	Werner syndrome RecQ like helicase
Mouse	Werner syndrome RecQ like helicase
Rat	Werner syndrome RecQ like helicase
Dog	Werner syndrome RecQ like helicase

Publication Statistics

PubMed Score 711.48

PubMed score by year

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PubTator Score 463.18

PubTator score by year

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Related Publications

Text Mined References (289)

GeneRif Annotations (218)

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PMID	Year	Title