Tchem DYRK3 Dual specificity tyrosine-phosphorylation-regulated kinase 3

Protein Summary

Description

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). This gene product belongs to the DYRK family of dual-specificity protein kinases that catalyze autophosphorylation on serine/threonine and tyrosine residues. The members of this family share structural similarity, however, differ in their substrate specificity, suggesting their involvement in different cellular functions. The encoded protein has been shown to autophosphorylate on tyrosine residue and catalyze phosphorylation of histones H3 and H2B in vitro. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• O43781
• D3DT79
• Q7Z752
• Q9HBY6
• Q9HBY7

Gene Name

• DYRK3

Ensembl ID

• ENST00000367106
• ENSP00000356073
• ENSG00000143479
• ENST00000367108
• ENSP00000356075
• ENST00000367109
• ENSP00000356076

Symbol

• RED
• REDK
• DYRK5
• hYAK3-2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.96
transcription factor binding site profile	0.94
virus perturbation	0.9
histone modification site profile	0.88
PubMedID	0.77

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Tyrosine Protein Kinase / Dual Specificity Tyrosine-phosphorylation-regulated Kinase 3

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Dual Specificity Tyrosine-phosphorylation-regulated Kinase 3

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Dyrk Family / Dyrk2 Subfamily / Dual Specificity Tyrosine-phosphorylation-regulated Kinase 3

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 33.25   (req: < 5)

Gene RIFs: 12   (req: <= 3)

Antibodies: 219   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 33.25   (req: >= 5)

Gene RIFs: 12   (req: > 3)

Antibodies: 219   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 20

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0