Human Recombinant DYRK2, Active protein, GST Tag (V2LY-0526-LY3664)

Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2

Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro).

Cellular response to DNA damage stimulus Source: UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
Negative regulation of calcineurin-NFAT signaling cascade Source: UniProtKB
Peptidyl-serine phosphorylation Source: GO_Central
Peptidyl-threonine phosphorylation Source: GO_Central
Positive regulation of glycogen biosynthetic process Source: UniProtKB
Protein phosphorylation Source: UniProtKB
Regulation of signal transduction by p53 class mediator Source: Reactome
Smoothened signaling pathway Source: UniProtKB

Nucleus; Cytoplasm. Translocates into the nucleus following DNA damage.

Autophosphorylates cotranslationally on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop, but once mature, does not have any protein tyrosine kinase activity. Phosphorylated at Thr-106 and Ser-442 by ATM in response to genotoxic stress.
Under normal conditions, polyubiquitinated in the nucleus by MDM2, leading to its proteasomal degradation. Phosphorylation on Thr-106 and Ser-442 by ATM in response to genotoxic stress disrupts MDM2 binding and prevents MDM2-mediated ubiquitination and subsequent proteasomal degradation. Polyubiquitinated by SIAH2, leading to its proteasomal degradation. Polyubiquitinated by SIAH2 ^oCcurs under normal conditions, and is enhanced in response to hypoxia.