DYRK2
Description
The DYRK2 (dual specificity tyrosine phosphorylation regulated kinase 2) is a protein-coding gene located on chromosome 12.
Dual specificity tyrosine-phosphorylation-regulated kinase 2 is an enzyme, in particular a dual-specificity kinase, that in humans is encoded by the DYRK2 gene. DYRK2 belongs to a family of protein kinases whose members are presumed to be involved in cellular growth and development. The family is defined by structural similarity of their kinase domains and their capability to autophosphorylate on tyrosine residues. DYRK2 has demonstrated tyrosine autophosphorylation and catalyzed phosphorylation of histones H3 and H2B in vitro. Two isoforms of DYRK2 have been isolated. The predominant isoform, isoform 1, lacks a 5' terminal insert.
DYRK2 is a serine/threonine-protein kinase that plays a crucial role in regulating various cellular processes, including the mitotic cell cycle, cell proliferation, apoptosis, cytoskeleton organization, and neurite outgrowth. Its functions are partly mediated through its involvement in ubiquitin-dependent proteasomal protein degradation. DYRK2 operates downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', contributing to the induction of apoptosis in response to DNA damage. It phosphorylates NFATC1, inhibiting its nuclear accumulation and transcription factor activity. DYRK2 phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Similarly, phosphorylation of NFATC1, CRMP2/DPYSL2, and CRMP4/DPYSL3 by DYRK2 promotes their subsequent phosphorylation by GSK3B. It may play a general role in priming GSK3 substrates. DYRK2 inactivates GYS1 by phosphorylation at 'Ser-641', potentially at a second site as well, thus regulating glycogen synthesis. It mediates EDVP E3 ligase complex formation and is essential for the phosphorylation and subsequent degradation of KATNA1. It phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. DYRK2 phosphorylates SIAH2, enhancing its ubiquitin ligase activity. It promotes the proteasomal degradation of MYC and JUN, thereby regulating mitotic cell cycle progression and cell proliferation. It also promotes the proteasomal degradation of GLI2 and GLI3, playing a role in smoothened and sonic hedgehog signaling. DYRK2 contributes to cytoskeleton organization and neurite outgrowth through its phosphorylation of DCX and DPYSL2. It phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT, and KATNA1. In vitro, DYRK2 can phosphorylate histone H1, histone H3, and histone H2B, as well as CARHSP1. It is a component of an E3 ligase complex containing DYRK2, EDD/UBR5, DDB1, and DCAF1 (EDVP complex). It directly interacts with EDD/UBR5, DDB1, and DCAF1, as well as SIAH2, MDM2, MAP3K10, and NFATC1. DYRK2 may also interact with CCNL2.
DYRK2 is also known as -.
