Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

DYRK3 (O43781) - Overview - Molecular Target Synopsis

Protein


DYRK3, Dual specificity tyrosine-phosphorylation-regulated kinase 3
Enzyme Classification 2.7.12.1
UniProt O43781

Also Known as DYRK3_HUMAN, DYRK3

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). Interacts with SIRT1.

5Y86
CRYSTAL STRUCTURE OF KINASE
RCSB/PDB
Inspect Structure
See all 3D Structures for DYRK3

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: DYRK3 is active in the following subcellular-locations: centrosome, cytoplasm, cytoplasmic granule, cytoskeleton, microtubule organizing center, nucleus, nucleus speckle.
GO terms: DYRK3 is active in the following subcellular-locations: cytoplasm, cytoplasmic stress granule, cytosol, intracellular membrane-bounded organelle, nuclear speck, nucleoplasm, nucleus, pericentriolar material.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project DYRK3 has gain in 3 cell-lines, loss in 1 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MDA_MB_435, A498, HOP_92

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hs 746T, KU812, OCI-LY-19

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HMEC, K562, AG445

(see details)

RNA Interference


DYRK3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OVAS, OVISE. (see details)

3D Structures


For DYRK3 there are:
1 structures (1 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


DYRK3 has been screened with 184 compounds (209 bioactivities), 11 compounds have bioactivities that show binding affinity of <= 500nM (11 bioactivities). (see details)