A bifunctional 3-5 exonuclease/ATP-dependent helicase WRN that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14191]
EC 3.6.4.12;
DNA helicase, RecQ-like type 3;
RecQ3;
Exonuclease WRN;
3.1.-.-;
RecQ protein-like 2
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 0 (0.00) | 29.6817 |
| 2010's | 2 (100.00) | 24.3611 |
| 2020's | 0 (0.00) | 2.80 |
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|---|---|---|---|---|
| 1-(3,4-dichlorophenyl)-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea | Homo sapiens (human) | IC50 | 3.4000 | 1 | 1 |
| 1-[4-fluoro-3-(trifluoromethyl)phenyl]-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea | Homo sapiens (human) | IC50 | 3.8500 | 2 | 2 |
This protein enables 25 target(s):
| Target | Category | Definition |
|---|---|---|
| magnesium ion binding | molecular function | Binding to a magnesium (Mg) ion. [GOC:ai] |
| four-way junction DNA binding | molecular function | Binding to a DNA segment containing four-way junctions, also known as Holliday junctions, a structure where two DNA double strands are held together by reciprocal exchange of two of the four strands, one strand each from the two original helices. [GOC:krc, ISBN:0815332181, PMID:15563464] |
| Y-form DNA binding | molecular function | Binding to a DNA segment shaped like a Y. This shape occurs when DNA contains a region of paired double-stranded DNA on one end and a region of unpaired DNA strands on the opposite end. [GOC:elh, PMID:16781730] |
| bubble DNA binding | molecular function | Binding to DNA segment that contains a bubble. A bubble occurs when DNA contains a region of unpaired, single-stranded DNA flanked on both sides by regions of paired, double-stranded DNA. [GOC:elh, GOC:vw, PMID:16781730] |
| DNA binding | molecular function | Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid). [GOC:dph, GOC:jl, GOC:tb, GOC:vw] |
| DNA helicase activity | molecular function | Unwinding of a DNA helix, driven by ATP hydrolysis. [GOC:jl] |
| chromatin binding | molecular function | Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase. [GOC:jl, ISBN:0198506732, PMID:20404130] |
| exonuclease activity | molecular function | Catalysis of the hydrolysis of ester linkages within nucleic acids by removing nucleotide residues from the 3' or 5' end. [GOC:mah, ISBN:0198547684] |
| protein binding | molecular function | Binding to a protein. [GOC:go_curators] |
| ATP binding | molecular function | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. [ISBN:0198506732] |
| 3'-5' exonuclease activity | molecular function | Catalysis of the hydrolysis of ester linkages within nucleic acids by removing nucleotide residues from the 3' end. [GOC:ai] |
| four-way junction helicase activity | molecular function | Unwinding a DNA helix of DNA containing four-way junctions, including Holliday junctions, driven by ATP hydrolysis. [GOC:al, PMID:22723423, PMID:9442895] |
| isomerase activity | molecular function | Catalysis of the geometric or structural changes within one molecule. Isomerase is the systematic name for any enzyme of EC class 5. [ISBN:0198506732] |
| ATP hydrolysis activity | molecular function | Catalysis of the reaction: ATP + H2O = ADP + H+ phosphate. ATP hydrolysis is used in some reactions as an energy source, for example to catalyze a reaction or drive transport against a concentration gradient. [RHEA:13065] |
| manganese ion binding | molecular function | Binding to a manganese ion (Mn). [GOC:ai] |
| MutLalpha complex binding | molecular function | Binding to a MutLalpha mismatch repair complex. [GOC:vk] |
| protein homodimerization activity | molecular function | Binding to an identical protein to form a homodimer. [GOC:jl] |
| 3'-5' DNA helicase activity | molecular function | Unwinding a DNA helix in the direction 5' to 3', driven by ATP hydrolysis. [EC:5.6.2.4, GOC:jl] |
| protein-containing complex binding | molecular function | Binding to a macromolecular complex. [GOC:jl] |
| G-quadruplex DNA binding | molecular function | Binding to G-quadruplex DNA structures, in which groups of four guanines adopt a flat, cyclic Hoogsteen hydrogen-bonding arrangement known as a guanine tetrad. The stacking of guanine tetrads results in G-quadruplex DNA structures. G-quadruplex DNA can form under physiological conditions from some G-rich sequences, such as those found in telomeres, immunoglobulin switch regions, gene promoters, fragile X repeats, and the dimerization domain in the human immunodeficiency virus (HIV) genome. [PMID:16142245, PMID:9512530] |
| forked DNA-dependent helicase activity | molecular function | Unwinding a DNA helix containing forked DNA, driven by ATP hydrolysis. [GOC:dph, PMID:26277776] |
| telomeric D-loop binding | molecular function | Binding to a telomeric D-loop. A telomeric D-loop is a three-stranded DNA displacement loop that forms at the site where the telomeric 3' single-stranded DNA overhang (formed of the repeat sequence TTAGGG in mammals) is tucked back inside the double-stranded component of telomeric DNA molecule, thus forming a t-loop or telomeric-loop and protecting the chromosome terminus. [GOC:BHF, GOC:BHF_telomere, GOC:nc, PMID:19734539] |
| telomeric G-quadruplex DNA binding | molecular function | Binding to telomeric G-quadruplex DNA structures, in which groups of four guanines adopt a flat, cyclic Hoogsteen hydrogen-bonding arrangement known as a guanine tetrad. The stacking of guanine tetrads results in G-quadruplex DNA structures in telomeres. [GOC:BHF, GOC:BHF_telomere, GOC:nc, PMID:16142245, PMID:9512530] |
| 3'-flap-structured DNA binding | molecular function | Binding to a 3'-flap structure in DNA. A DNA flap structure is one in which a single-stranded 3'-end of DNA or RNA protrudes from a double-stranded DNA molecule. [GOC:mah, PMID:15189154] |
| 8-hydroxy-2'-deoxyguanosine DNA binding | molecular function | Binding to 8-hydroxy-2'-deoxyguanosine an oxidized purine residue found in damaged DNA. [GO_REF:0000067, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:19734539] |
This protein is located in 6 target(s):
| Target | Category | Definition |
|---|---|---|
| chromosome, telomeric region | cellular component | The end of a linear chromosome, required for the integrity and maintenance of the end. A chromosome telomere usually includes a region of telomerase-encoded repeats the length of which rarely exceeds 20 bp each and that permits the formation of a telomeric loop (T-loop). The telomeric repeat region is usually preceded by a sub-telomeric region that is gene-poor but rich in repetitive elements. Some telomeres only consist of the latter part (for eg. D. melanogaster telomeres). [GOC:elh] |
| nucleoplasm | cellular component | That part of the nuclear content other than the chromosomes or the nucleolus. [GOC:ma, ISBN:0124325653] |
| replication fork | cellular component | The Y-shaped region of a replicating DNA molecule, resulting from the separation of the DNA strands and in which the synthesis of new strands takes place. Also includes associated protein complexes. [GOC:mah, ISBN:0198547684] |
| nucleolus | cellular component | A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome. [ISBN:0198506732] |
| centrosome | cellular component | A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle. [GOC:mah, ISBN:0198547684] |
| nuclear speck | cellular component | A discrete extra-nucleolar subnuclear domain, 20-50 in number, in which splicing factors are seen to be localized by immunofluorescence microscopy. [http://www.cellnucleus.com/] |
This protein is active in 4 target(s):
| Target | Category | Definition |
|---|---|---|
| chromosome | cellular component | A structure composed of a very long molecule of DNA and associated proteins (e.g. histones) that carries hereditary information. [ISBN:0198547684] |
| nucleus | cellular component | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. [GOC:go_curators] |
| cytoplasm | cellular component | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684] |
| nucleoplasm | cellular component | That part of the nuclear content other than the chromosomes or the nucleolus. [GOC:ma, ISBN:0124325653] |
This protein is involved in 24 target(s):
| Target | Category | Definition |
|---|---|---|
| telomere maintenance | biological process | Any process that contributes to the maintenance of proper telomeric length and structure by affecting and monitoring the activity of telomeric proteins, the length of telomeric DNA and the replication and repair of the DNA. These processes includes those that shorten, lengthen, replicate and repair the telomeric DNA sequences. [GOC:BHF, GOC:BHF_telomere, GOC:elh, GOC:rl, PMID:11092831] |
| DNA synthesis involved in DNA repair | biological process | Synthesis of DNA that proceeds from the broken 3' single-strand DNA end and uses the homologous intact duplex as the template. [PMID:10357855] |
| DNA metabolic process | biological process | Any cellular metabolic process involving deoxyribonucleic acid. This is one of the two main types of nucleic acid, consisting of a long, unbranched macromolecule formed from one, or more commonly, two, strands of linked deoxyribonucleotides. [ISBN:0198506732] |
| DNA replication | biological process | The cellular metabolic process in which a cell duplicates one or more molecules of DNA. DNA replication begins when specific sequences, known as origins of replication, are recognized and bound by the origin recognition complex, and ends when the original DNA molecule has been completely duplicated and the copies topologically separated. The unit of replication usually corresponds to the genome of the cell, an organelle, or a virus. The template for replication can either be an existing DNA molecule or RNA. [GOC:mah] |
| base-excision repair | biological process | In base excision repair, an altered base is removed by a DNA glycosylase enzyme, followed by excision of the resulting sugar phosphate. The small gap left in the DNA helix is filled in by the sequential action of DNA polymerase and DNA ligase. [ISBN:0815316194] |
| double-strand break repair | biological process | The repair of double-strand breaks in DNA via homologous and nonhomologous mechanisms to reform a continuous DNA helix. [GOC:elh] |
| DNA damage response | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to its DNA from environmental insults or errors during metabolism. [GOC:go_curators] |
| response to oxidative stress | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals. [GOC:jl, PMID:12115731] |
| determination of adult lifespan | biological process | The pathways that regulate the duration of the adult phase of the life-cycle of an animal. [PMID:25561524, PMID:273723695, PMID:3424805] |
| response to UV-C | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a UV-C radiation stimulus. UV-C radiation (UV-C light) spans the wavelengths 100 to 280 nm. [GOC:tb] |
| replication fork processing | biological process | The process in which a DNA replication fork that has stalled is restored to a functional state and replication is restarted. The stalling may be due to DNA damage, DNA secondary structure, bound proteins, dNTP shortage, or other causes. [GOC:vw, PMID:11459955, PMID:15367656, PMID:17660542] |
| telomere maintenance via semi-conservative replication | biological process | The process in which telomeric DNA is synthesized semi-conservatively by the conventional replication machinery and telomeric accessory factors as part of cell cycle DNA replication. [GOC:BHF, GOC:BHF_telomere, GOC:rl, GOC:vw, PMID:16598261] |
| DNA duplex unwinding | biological process | The process in which interchain hydrogen bonds between two strands of DNA are broken or 'melted', generating a region of unpaired single strands. [GOC:isa_complete, GOC:mah] |
| regulation of growth rate | biological process | Any process that modulates the rate of growth of all or part of an organism. [GOC:mah] |
| G-quadruplex DNA unwinding | biological process | The process by which G-quadruplex (also known as G4) DNA, which is a four-stranded DNA structure held together by guanine base pairing, is unwound or 'melted'. [GOC:jl, GOC:se, PMID:23657261] |
| positive regulation of hydrolase activity | biological process | Any process that activates or increases the frequency, rate or extent of hydrolase activity, the catalysis of the hydrolysis of various bonds. [GOC:ai] |
| telomeric D-loop disassembly | biological process | A telomere loop disassembly process that results in the disassembly of telomeric D-loops. A telomeric D-loop is a three-stranded DNA displacement loop that forms at the site where the telomeric 3' single-stranded DNA overhang (formed of the repeat sequence TTAGGG in mammals) is tucked back inside the double-stranded component of telomeric DNA molecule, thus forming a t-loop or telomeric-loop and protecting the chromosome terminus. [GOC:BHF, GOC:BHF_telomere, GOC:nc, PMID:10338204, PMID:24012755] |
| cellular response to gamma radiation | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a gamma radiation stimulus. Gamma radiation is a form of electromagnetic radiation (EMR) or light emission of a specific frequency produced from sub-atomic particle interaction, such as electron-positron annihilation and radioactive decay. Gamma rays are generally characterized as EMR having the highest frequency and energy, and also the shortest wavelength, within the electromagnetic radiation spectrum. [GOC:mah] |
| cellular senescence | biological process | A cell aging process stimulated in response to cellular stress, whereby normal cells lose the ability to divide through irreversible cell cycle arrest. [GOC:BHF, PMID:28682291] |
| replicative senescence | biological process | A cell aging process associated with the dismantling of a cell as a response to telomere shortening and/or cellular aging. [GOC:BHF] |
| t-circle formation | biological process | A telomere maintenance process that results in the formation of a telomeric circle, or t-circle. A t-circle is an extrachromosomal duplex or single-stranded circular DNA molecule composed of t-arrays. T-circles are involved in the control of telomere length via alternative-lengthening of telomeres (ALT) pathway and telomere rapid deletion (TRD). [GOC:BHF, GOC:BHF_telomere, GOC:nc, PMID:19214183, PMID:19581589, PMID:19809492, PMID:19858100] |
| positive regulation of strand invasion | biological process | Any process that increases the rate, frequency or extent of strand invasion. Strand invasion is the process in which the nucleoprotein complex (composed of the broken single-strand DNA and the recombinase) searches and identifies a region of homology in intact duplex DNA. The broken single-strand DNA displaces the like strand and forms Watson-Crick base pairs with its complement, forming a duplex in which each strand is from one of the two recombining DNA molecules. [GOC:dos, GOC:dph, GOC:elh, GOC:tb] |
| DNA unwinding involved in DNA replication | biological process | The process in which interchain hydrogen bonds between two strands of DNA are broken or 'melted', generating unpaired template strands for DNA replication. [ISBN:071673706X, ISBN:0815316194] |
| double-strand break repair via homologous recombination | biological process | The error-free repair of a double-strand break in DNA in which the broken DNA molecule is repaired using homologous sequences. A strand in the broken DNA searches for a homologous region in an intact chromosome to serve as the template for DNA synthesis. The restoration of two intact DNA molecules results in the exchange, reciprocal or nonreciprocal, of genetic material between the intact DNA molecule and the broken DNA molecule. [GOC:elh, PMID:10357855] |