InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: WRN

Summary

InnateDB Protein

IDBP-16094.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

WRN

Protein Name

Werner syndrome, RecQ helicase-like

Synonyms

RECQ3; RECQL2; RECQL3;

Species

Homo sapiens

Ensembl Protein

ENSP00000298139

InnateDB Gene

IDBG-16092 (WRN)

Protein Structure

UniProt Annotation

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). Plays a role in double-strand break repair after gamma-irradiation. {ECO:0000250, ECO:0000269PubMed:11863428, ECO:0000269PubMed:17563354, ECO:0000269PubMed:18596042, ECO:0000269PubMed:19283071, ECO:0000269PubMed:19652551, ECO:0000269PubMed:21639834}.

Subcellular Localization

Nucleus, nucleolus. Nucleus. Nucleus, nucleoplasm. Note=Gamma-irradiation leads to its translocation from nucleoli to nucleoplasm and PML regulates the irradiation- induced WRN relocation.

Disease Associations

Werner syndrome (WRN) [MIM:277700]: 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. {ECO:0000269PubMed:16673358}. Note=The disease is caused by mutations affecting the gene represented in this entry.Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The disease may be caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 69 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	69 [view]
Protein-Protein	68 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0000287	magnesium ion binding
GO:0000403	Y-form DNA binding
GO:0000405	bubble DNA binding
GO:0003676	nucleic acid binding
GO:0003677	DNA binding
GO:0003678	DNA helicase activity
GO:0003824	catalytic activity
GO:0004003	ATP-dependent DNA helicase activity
GO:0004386	helicase activity
GO:0004527	exonuclease activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008026	ATP-dependent helicase activity
GO:0008408	3'-5' exonuclease activity
GO:0009378	four-way junction helicase activity
GO:0016887	ATPase activity
GO:0030145	manganese ion binding
GO:0032403	protein complex binding
GO:0042803	protein homodimerization activity
GO:0043138	3'-5' DNA helicase activity
GO:0043140	ATP-dependent 3'-5' DNA helicase activity
GO:0051880	G-quadruplex DNA binding

Biological Process

GO:0000723	telomere maintenance
GO:0000731	DNA synthesis involved in DNA repair
GO:0001302	replicative cell aging
GO:0006139	nucleobase-containing compound metabolic process
GO:0006200	ATP catabolic process
GO:0006259	DNA metabolic process
GO:0006260	DNA replication
GO:0006281	DNA repair
GO:0006284	base-excision repair
GO:0006302	double-strand break repair
GO:0006310	DNA recombination
GO:0006974	cellular response to DNA damage stimulus
GO:0006979	response to oxidative stress
GO:0007568	aging
GO:0007569	cell aging
GO:0009267	cellular response to starvation
GO:0010225	response to UV-C
GO:0010259	multicellular organismal aging
GO:0031297	replication fork processing
GO:0032066	nucleolus to nucleoplasm transport
GO:0032508	DNA duplex unwinding
GO:0040009	regulation of growth rate
GO:0042981	regulation of apoptotic process
GO:0044237	cellular metabolic process
GO:0051345	positive regulation of hydrolase activity
GO:0071480	cellular response to gamma radiation
GO:0090305	nucleic acid phosphodiester bond hydrolysis

Cellular Component

GO:0005622	intracellular
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005730	nucleolus
GO:0005813	centrosome
GO:0032389	MutLalpha complex

Protein Structure and Domains

PDB ID

InterPro

IPR001650 Helicase, C-terminal
IPR002121 HRDC domain
IPR002562 3\'-5\' exonuclease domain
IPR004589 DNA helicase, ATP-dependent, RecQ type
IPR010997 HRDC-like
IPR011545 DEAD/DEAH box helicase domain
IPR012337 Ribonuclease H-like domain
IPR014001 Helicase, superfamily 1/2, ATP-binding domain
IPR018982 RQC domain
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00271
PF00570
PF01612
PF00270
PF09382

PRINTS

PIRSF

SMART

SM00490
SM00341
SM00474
SM00487
SM00956

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q14191