DYRK3 Antibody - #DF8760

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.

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.

Nucleus. Cytoplasm. Nucleus speckle. Cytoplasmic granule. Cytoplasm>Cytoskeleton>Microtubule organizing center>Centrosome.
Note: 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).

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.

Interacts with SIRT1.

The N-terminal domain, which is intrinsically disordered, is required for stress granule localization.

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.