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 .
Subcellular locations: Nucleus, Cytoplasm, Nucleus speckle, Cytoplasmic granule, Cytoplasm, Cytoskeleton, Microtubule organizing center, Centrosome
Associates with membraneless organelles in the cytoplasm and nucleus . Shuttles between cytoplasm and stress granules . Localized predominantly on distinct speckles distributed throughout the cytoplasm of the cell . 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 .
Isoform 1: Highly expressed in testis and in hematopoietic tissue such as fetal liver, and bone marrow . Isoform 1: Predominant form in fetal liver and bone marrow . Isoform 1: Present at low levels in heart, pancreas, lymph node and thymus . Isoform 2: Highly expressed in testis and in hematopoietic tissue such as fetal liver, and bone marrow . Isoform 2: Predominant form in testis. Isoform 2: Present at low levels in heart, pancreas, lymph node and thymus .