DYRK3

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]

Full Name

dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 3

Research Area

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).

Biological Process

Cell cycle Source: UniProtKB-KW
Cell division Source: UniProtKB-KW
Erythrocyte differentiation Source: UniProtKB
Negative regulation of apoptotic process Source: Ensembl
Negative regulation of DNA damage response, signal transduction by p53 class mediator Source: Ensembl
Nuclear speck organization Source: UniProtKB
Organelle disassembly Source: UniProtKB
Peptidyl-serine phosphorylation Source: GO_Central
Peptidyl-threonine phosphorylation Source: GO_Central
Positive regulation of cell cycle G2/M phase transition Source: UniProtKB
Protein phosphorylation Source: UniProtKB
Regulation of cellular response to stress Source: UniProtKB
Regulation of TORC1 signaling Source: UniProtKB
Stress granule disassembly Source: UniProtKB

Cellular Location

Cytoplasm; Nucleus; Nucleus speckle; Centrosome; Cytoplasmic granule. Associates with membraneless organelles in the cytoplasm and nucleus (PubMed:29973724). Shuttles between cytoplasm and stress granules (PubMed:20167603). Localized predominantly on distinct speckles distributed throughout the cytoplasm of the cell (PubMed:20167603). At low concentration, showns a homogeneous distribution throughout the cytoplasm and does not condense in speckles. During oxidative and osmotic stress, localizes to stress granules (PubMed:20167603).

PTM

Ubiquitinated at anaphase by the anaphase-promoting complex (APC/C), leading to its degradation by the proteasome.
Protein kinase activity is activated following autophosphorylation at Tyr-369 (Probable). Autophosphorylation at Ser-350 stabilizes the protein and enhances the protein kinase activity (PubMed:9748265).