UniProt functional annotation for Q14191



	UniProt functional annotation for Q14191

UniProt code: Q14191.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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:0000269|PubMed:11863428, ECO:0000269|PubMed:17563354, ECO:0000269|PubMed:18596042, ECO:0000269|PubMed:19283071, ECO:0000269|PubMed:19652551, ECO:0000269|PubMed:21639834}.

Catalytic activity: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; Evidence={ECO:0000269|PubMed:16622405};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:16622405}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:16622405}; Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:16622405}; Note=Binds 2 magnesium ions per subunit. Has high activity with manganese and zinc ions (in vitro). {ECO:0000269|PubMed:16622405};

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. Interacts with PML (isoform PML-4). {ECO:0000250, ECO:0000269|PubMed:11863428, ECO:0000269|PubMed:12704184, ECO:0000269|PubMed:17961633, ECO:0000269|PubMed:18596042, ECO:0000269|PubMed:20159463, ECO:0000269|PubMed:21639834}.

Subcellular location: Nucleus, nucleolus {ECO:0000269|PubMed:9618508}. Nucleus {ECO:0000269|PubMed:17563354, ECO:0000269|PubMed:19652551}. Nucleus, nucleoplasm {ECO:0000269|PubMed:21639834}. Note=Gamma- irradiation leads to its translocation from nucleoli to nucleoplasm and PML regulates the irradiation-induced WRN relocation. {ECO:0000269|PubMed:21639834}.

Ptm: Phosphorylated by PRKDC. {ECO:0000269|PubMed:11889123}.

Disease: 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:0000269|PubMed:16673358}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: 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. {ECO:0000305|PubMed:24308539, ECO:0000305|PubMed:9989816}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the helicase family. RecQ subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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:0000269\|PubMed:11863428, ECO:0000269\|PubMed:17563354, ECO:0000269\|PubMed:18596042, ECO:0000269\|PubMed:19283071, ECO:0000269\|PubMed:19652551, ECO:0000269\|PubMed:21639834}.


Catalytic activity:		Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; Evidence={ECO:0000269\|PubMed:16622405};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:16622405}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269\|PubMed:16622405}; Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269\|PubMed:16622405}; Note=Binds 2 magnesium ions per subunit. Has high activity with manganese and zinc ions (in vitro). {ECO:0000269\|PubMed:16622405};
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. Interacts with PML (isoform PML-4). {ECO:0000250, ECO:0000269\|PubMed:11863428, ECO:0000269\|PubMed:12704184, ECO:0000269\|PubMed:17961633, ECO:0000269\|PubMed:18596042, ECO:0000269\|PubMed:20159463, ECO:0000269\|PubMed:21639834}.
Subcellular location:		Nucleus, nucleolus {ECO:0000269\|PubMed:9618508}. Nucleus {ECO:0000269\|PubMed:17563354, ECO:0000269\|PubMed:19652551}. Nucleus, nucleoplasm {ECO:0000269\|PubMed:21639834}. Note=Gamma- irradiation leads to its translocation from nucleoli to nucleoplasm and PML regulates the irradiation-induced WRN relocation. {ECO:0000269\|PubMed:21639834}.
Ptm:		Phosphorylated by PRKDC. {ECO:0000269\|PubMed:11889123}.
Disease:		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:0000269\|PubMed:16673358}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		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. {ECO:0000305\|PubMed:24308539, ECO:0000305\|PubMed:9989816}. Note=The disease may be caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the helicase family. RecQ subfamily. {ECO:0000305}.