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

DYRK1A (Q13627) - Overview - Molecular Target Synopsis

Protein


DYRK1A, Dual specificity tyrosine-phosphorylation-regulated kinase 1A
Enzyme Classification 2.7.12.1
UniProt Q13627

Also Known as DYR1A_HUMAN, DYRK1A, DYRK, MNB, MNBH

Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Exhibits a substrate preference for proline at position P+1 and arginine at position P-3. Has pro-survival function and negatively regulates the apoptotic process. Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1. This in turn inhibits TP53 activity and apoptosis. Interacts RAD54L2/ARIP4 (By similarity). Interacts with CRY2 (By similarity). Interacts with RANBP9 (PubMed:14500717). Interacts with WDR68 (PubMed:14593110). Interacts with SRSF6 (PubMed:22767602). Interacts with SIRT1.

6A1G
CRYSTAL STRUCTURE OF HUMAN DYRK1A IN COMPLEX WITH COMPOUND 32
RCSB/PDB
Inspect Structure
See all 3D Structures for DYRK1A

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: DYRK1A is active in the following subcellular-locations: nucleus, nucleus speckle.
GO terms: DYRK1A is active in the following subcellular-locations: axon, cytoplasm, cytoskeleton, dendrite, nuclear speck, nucleoplasm, nucleus, ribonucleoprotein complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project DYRK1A has gain in 1 cell-lines, loss in 2 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: CCRF_CEM, K_562, HL_60

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SET-2, HEL, NCI-H345

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: HSMM, NHLF, SK-N-SH

(see details)

RNA Interference


DYRK1A was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CROE33, BXPC3. (see details)

3D Structures


For DYRK1A there are:
30 structures (106 chains) solved
30 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

DYRK1A is solved in complex with the approved drug(s):

2K2/MIDOSTAURIN (4NCT_A, 4NCT_B, 4NCT_C, 4NCT_D).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


DYRK1A has been screened with 1352 compounds (1948 bioactivities), 177 compounds have bioactivities that show binding affinity of <= 500nM (239 bioactivities). (see details)