Dual specificity tyrosine-phosphorylation-regulated kinase

spinqualitylabelsall models Human DYRK1A kinase domain containing a phosphorylated Tyr residue complex with inhibitor (PDB code 6eij) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Function Dual specificity tyrosine-phosphorylation-regulated kinase (DYRK) is a member of a 5-member family of evolutionary conserved protein kinases. DYRK1A is associated with both neuropathological phenotypes and cancer susceptibility in patients with Down syndrome. DYRK2 is a 26S proteasome-regulating kinase. DYRK3 interacts with proteins associated with endoplasmic reticulum exit sites. Relevance DYRK1A protects against insulin resistance in the brain by elevating insulin receptor substrate 1 expression. DYRK1A inhibitors attenuate cognitive dysfunction in animal models for Down syndrome and Alzheimer Disease. DYRK1A is a potential cancer therapeutic target because of its role in the regulation of cell cycle progression by affecting both tumor suppressors and oncogenes. Some DYRK1A inhibitors block the tau phosphorylation that is a hallmark of Alzheimer's disease. DYRK2 is a therapeutic target for multiple myeloma and triple-negative breast cancer. Structural highlights The complex of human DYRK1A kinase domain with an inhibitor shows numerous interactions between the protein ATP pocket and the inhibitor including with the catalytic Lys residue and the gatekeeper Phe residue. The gatekeeper Phe is a vital residue which is responsible for the selectivity of inhibitors. 3D structures of dual specificity tyrosine-phosphorylation-regulated kinase Dual specificity tyrosine-phosphorylation-regulated kinase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky