General Information of the Protein
Protein ID
PT01114
Protein Name
Dual specificity tyrosine-phosphorylation-regulated kinase 3
Secondarily
Protein Name
Regulatory erythroid kinase
Gene Name
DYRK3
Sequence
MGGTARGPGRKDAGPPGAGLPPQQRRLGDGVYDTFMMIDETKCPPCSNVLCNPSEPPPPRRLNMTTEQFTGDHTQHFLDGGEMKVEQLFQEFGNRKSNTIQSDGISDSEKCSPTVSQGKSSDCLNTVKSNSSSKAPKVVPLTPEQALKQYKHHLTAYEKLEIINYPEIYFVGPNAKKRHGVIGGPNNGGYDDADGAYIHVPRDHLAYRYEVLKIIGKGSFGQVARVYDHKLRQYVALKMVRNEKRFHRQAAEEIRILEHLKKQDKTGSMNVIHMLESFTFRNHVCMAFELLSIDLYELIKKNKFQGFSVQLVRKFAQSILQSLDALHKNKIIHCDLKPENILLKHHGRSSTKVIDFGSSCFEYQKLYTYIQSRFYRAPEIILGSRYSTPIDIWSFGCILAELLTGQPLFPGEDEGDQLACMMELLGMPPPKLLEQSKRAKYFINSKGIPRYCSVTTQADGRVVLVGGRSRRGKKRGPPGSKDWGTALKGCDDYLFIEFLKRCLHWDPSARLTPAQALRHPWISKSVPRPLTTIDKVSGKRVVNPASAFQGLGSKLPPVVGIANKLKANLMSETNGSIPLCSVLPKLIS
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
CMGC protein kinase group
>
CMGC protein kinase DYRK family
>
CMGC protein kinase Dyrk2 subfamily
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 (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:9748265, PubMed:29634919). 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 (PubMed:29973724). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724). 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 (PubMed:29973724). 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 (PubMed:23415227). 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 (PubMed:23415227). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603).
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Uniprot ID
Primary ID:
O43781

Secondarily ID:
D3DT79
Q7Z752
Q9HBY6
Q9HBY7
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HGNC ID
HGNC:3094
Subcellular Location
Nucleus
Cytoplasm
Nucleus speckle
Cytoplasmic granule
Cytoplasm
Cytoskeleton
Microtubule organizing center
Centrosome
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000013 , Sf9
Compound ID Compound Name Compound Formula
CP0935565
2-(5-Amino-2-chloro-phenylamino)-5-quinolin-6-ylmethylene-thiazol-4-one
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C19H13ClN4OS
 1
1
IC50 = 1 nM
   TI
   LI
   LO
   TS
CP0953425
2-(2-Bromo-phenylimino)-5-(quinolin-6-ylmethylene)-thiazolidin-4-one
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C19H12BrN3OS
 1
1
IC50 = 1 nM
   TI
   LI
   LO
   TS
CP0968896
2-(2-Chloro-phenylimino)-5-quinolin-6-ylmethylene-thiazolidin-4-one
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C19H12ClN3OS
 1
1
IC50 = 10 nM
   TI
   LI
   LO
   TS
CP0967600
2-(2-Trifluoromethyl-phenylimino)-5-(2,3-dihydrobenzofuran-5-ylmethylene)-thiazolidin-4-one
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C19H13F3N2O2S
 1
1
IC50 = 100 nM
   TI
   LI
   LO
   TS
CP0967601
2-(2-Dimethylamino-ethylimino)-5-quinolin-6-ylmethylene-thiazolidin-4-one
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C17H18N4OS
 1
1
IC50 = 1000 nM
   TI
   LI
   LO
   TS
Clinical Information about the Protein
Target 1 ( Dual-specificity tyrosine-phosphorylation regulated kinase 3 (DYRK3) )
Target Type Patented-recorded Target