Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

DYRK2 (Q92630) - Overview - Molecular Target Synopsis

Protein


DYRK2, Dual specificity tyrosine-phosphorylation-regulated kinase 2
Enzyme Classification 2.7.12.1
UniProt Q92630

Also Known as DYRK2_HUMAN, DYRK2

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). Component of an E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 (EDVP complex). Interacts directly with EDD/UBR5, DDB1 and DCAF1. Interacts with SIAH2 and MDM2. Interacts with MAP3K10 and NFATC1. May also interact with CCNL2.

5ZTN
THE CRYSTAL STRUCTURE OF HUMAN DYRK2 IN COMPLEX WITH CURCUMIN
RCSB/PDB
Inspect Structure
See all 3D Structures for DYRK2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: DYRK2 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: DYRK2 is active in the following subcellular-locations: cytoplasm, cytosol, nucleoplasm, nucleus, ribonucleoprotein complex, ubiquitin ligase complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project DYRK2 has gain in 5 cell-lines, loss in 2 cell-lines and no signal in 998 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: OVCAR_4, OVCAR_3, BT_549

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC1143, OAW28, MKN-45

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, HSMM, NHLF

(see details)

RNA Interference


DYRK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SKBR3, OVTOKO. (see details)

3D Structures


For DYRK2 there are:
6 structures (9 chains) solved
5 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


DYRK2 has been screened with 888 compounds (1491 bioactivities), 44 compounds have bioactivities that show binding affinity of <= 500nM (48 bioactivities). (see details)