General Information of Target

Target ID LDTP00867
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
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGGTARGPGRKDAGPPGAGLPPQQRRLGDGVYDTFMMIDETKCPPCSNVLCNPSEPPPPR
RLNMTTEQFTGDHTQHFLDGGEMKVEQLFQEFGNRKSNTIQSDGISDSEKCSPTVSQGKS
SDCLNTVKSNSSSKAPKVVPLTPEQALKQYKHHLTAYEKLEIINYPEIYFVGPNAKKRHG
VIGGPNNGGYDDADGAYIHVPRDHLAYRYEVLKIIGKGSFGQVARVYDHKLRQYVALKMV
RNEKRFHRQAAEEIRILEHLKKQDKTGSMNVIHMLESFTFRNHVCMAFELLSIDLYELIK
KNKFQGFSVQLVRKFAQSILQSLDALHKNKIIHCDLKPENILLKHHGRSSTKVIDFGSSC
FEYQKLYTYIQSRFYRAPEIILGSRYSTPIDIWSFGCILAELLTGQPLFPGEDEGDQLAC
MMELLGMPPPKLLEQSKRAKYFINSKGIPRYCSVTTQADGRVVLVGGRSRRGKKRGPPGS
KDWGTALKGCDDYLFIEFLKRCLHWDPSARLTPAQALRHPWISKSVPRPLTTIDKVSGKR
VVNPASAFQGLGSKLPPVVGIANKLKANLMSETNGSIPLCSVLPKLIS
Target Type
Patented-recorded
Target Bioclass
Enzyme
Family
Protein kinase superfamily, CMGC Ser/Thr protein kinase family, MNB/DYRK subfamily
Subcellular location
Nucleus
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.
TTD ID
T97149
Uniprot ID
O43781
DrugMap ID
TTV4EX0
Ensemble ID
ENST00000367106.1
HGNC ID
HGNC:3094
ChEMBL ID
CHEMBL4575

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
AN3CA Deletion: p.N302IfsTer35 .
CASKI SNV: p.R10Q .
JVM3 SNV: p.L20I .
KYSE410 SNV: p.Q117Ter .
OSRC2 SNV: p.A400V .
PF382 SNV: p.L62V .
SKMEL2 SNV: p.M239L .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C43(1.12); C46(1.12); C51(1.12)  LDD0078  [1]
CY-1
 Probe Info 
Y165(0.00); Y169(0.00)  LDD0246  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0020  ARS-1620 HCC44 C43(1.12); C46(1.12); C51(1.12)  LDD0078  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Golgi reassembly-stacking protein 2 (GORASP2) GORASP family Q9H8Y8

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pmid24900749c1a Small molecular drug D04TPA
Patented
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Harmine Small molecular drug D00OWF
Pmid28766366-compound-scheme21left Small molecular drug D02DBH
Pmid28766366-compound-scheme21right Small molecular drug D07BWC

References

1 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
2 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.