Dual specificity tyrosine-phosphorylation-regulated kinase 3

Dual specificity tyrosine-phosphorylation-regulated kinase 3

Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material29973724. Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues29634919,9748265. 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 PCM129973724. Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK329973724. 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 mitosis29973724. 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 signaling23415227. 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 signaling23415227. Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis10779429. Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells10779429. Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis20167603

Quoted from UniProt’s FUNCTION annotation for O43781 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Nucleoplasm
• Cytosoladditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Nucleus · Cytoplasm · Nucleus speckle · Cytoplasmic granule · Cytoplasm, cytoskeleton, microtubule organizing center, centrosome

Expression by cell type

Single cell type RNA, the 4 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Late primary spermatocytes364.5 nCPM
• Early spermatids214 nCPM
• Erythrocyte progenitors91 nCPM
• Salivary basal cells89.8 nCPM

Expression by tissue

The tissues this gene is enriched in, by consensus RNA. A tissue absent from this list is one the Atlas does not call specific for this gene, which is not the same as absent from it.

• testis44.8 nTPM