Details of the Target
General Information of Target
Target ID | LDTP00867 | |||||
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Target Name | Dual specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3) | |||||
Gene Name | DYRK3 | |||||
Gene ID | 8444 | |||||
Synonyms |
Dual specificity tyrosine-phosphorylation-regulated kinase 3; EC 2.7.12.1; Regulatory erythroid kinase; REDK |
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3D Structure | ||||||
Sequence |
MGGTARGPGRKDAGPPGAGLPPQQRRLGDGVYDTFMMIDETKCPPCSNVLCNPSEPPPPR
RLNMTTEQFTGDHTQHFLDGGEMKVEQLFQEFGNRKSNTIQSDGISDSEKCSPTVSQGKS SDCLNTVKSNSSSKAPKVVPLTPEQALKQYKHHLTAYEKLEIINYPEIYFVGPNAKKRHG VIGGPNNGGYDDADGAYIHVPRDHLAYRYEVLKIIGKGSFGQVARVYDHKLRQYVALKMV RNEKRFHRQAAEEIRILEHLKKQDKTGSMNVIHMLESFTFRNHVCMAFELLSIDLYELIK KNKFQGFSVQLVRKFAQSILQSLDALHKNKIIHCDLKPENILLKHHGRSSTKVIDFGSSC FEYQKLYTYIQSRFYRAPEIILGSRYSTPIDIWSFGCILAELLTGQPLFPGEDEGDQLAC MMELLGMPPPKLLEQSKRAKYFINSKGIPRYCSVTTQADGRVVLVGGRSRRGKKRGPPGS KDWGTALKGCDDYLFIEFLKRCLHWDPSARLTPAQALRHPWISKSVPRPLTTIDKVSGKR VVNPASAFQGLGSKLPPVVGIANKLKANLMSETNGSIPLCSVLPKLIS |
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Target Type |
Patented-recorded
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Target Bioclass |
Enzyme
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Family |
Protein kinase superfamily, CMGC Ser/Thr protein kinase family, MNB/DYRK subfamily
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Subcellular location |
Nucleus
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Function |
Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material. Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues. Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1. Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3. Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis. Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling. When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling. Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis. Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells. Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis.
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TTD ID | ||||||
Uniprot ID | ||||||
DrugMap ID | ||||||
Ensemble ID | ||||||
HGNC ID | ||||||
ChEMBL ID |
Target Site Mutations in Different Cell Lines
Probe(s) Labeling This Target
ABPP Probe
Probe name | Structure | Binding Site(Ratio) | Interaction ID | Ref | |
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DBIA Probe Info |
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C43(1.12); C46(1.12); C51(1.12) | LDD0078 | [1] | |
CY-1 Probe Info |
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Y165(0.00); Y169(0.00) | LDD0246 | [2] |
Competitor(s) Related to This Target
The Interaction Atlas With This Target
The Protein(s) Related To This Target
Other
Protein name | Family | Uniprot ID | |||
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Golgi reassembly-stacking protein 2 (GORASP2) | GORASP family | Q9H8Y8 |
The Drug(s) Related To This Target
Investigative
Drug Name | Drug Type | External ID | |||
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Pmid24900749c1a | Small molecular drug | D04TPA |
Patented
Drug Name | Drug Type | External ID | |||
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Harmine | Small molecular drug | D00OWF | |||
Pmid28766366-compound-scheme21left | Small molecular drug | D02DBH | |||
Pmid28766366-compound-scheme21right | Small molecular drug | D07BWC |
References