DYRK2 Antibody – Rabbit Polyclonal

DYRK2 belongs to a family of protein kinases whose members are presumed to be involved in cellular growth and/or 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. [provided by RefSeq, Jul 2008]

Function: 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 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). Ref.1 Ref.6 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.19 Ref.22 Ref.23

Catalytic activity: ATP + a protein = ADP + a phosphoprotein.

Cofactor: Magnesium. Ref.1Manganese. Ref.1

Enzyme regulation: Activated by autophosphorylation on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop. Inhibited by acridine analogs, purvalanol, and barely by harmine. Inhibited by leucettine and leucettine derivatives. Ref.12 Ref.18 Ref.20 Ref.25

Subunit structure: Component of an E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and VPRBP (EDVP complex). Interacts directly with EDD/UBR5, DDB1 and VPRBP. Interacts with SIAH2 and MDM2. Interacts with MAP3K10 and NFATC1. May also interact with CCNL2. Ref.10 Ref.13 Ref.19 Ref.21

Subcellular location: Cytoplasm. Nucleus. Note: Translocates into the nucleus following DNA damage. Ref.14 Ref.15 Ref.17 Ref.21

Tissue specificity: Testis, after the onset of spermatogenesis. Ref.1

Induction: Accumulates in nucleus upon DNA damage. Induced in both esophageal and lung adenocarcinomas. Ref.7 Ref.12 Ref.18 Ref.20 Ref.21 Ref.25

Post-translational modification: 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. Ref.1 Ref.15 Ref.16 Ref.21 Ref.25Under 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.

Sequence similarities: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.Contains 1 protein kinase domain.

Sequence caution: The sequence CAA73885.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.