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

DAPK1 (P53355) - Overview - Molecular Target Synopsis

Protein


DAPK1, Death-associated protein kinase 1
Enzyme Classification 2.7.11.1
UniProt P53355

Also Known as DAPK1_HUMAN, DAPK1, DAPK

Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition., Isoform 2 cannot induce apoptosis but can induce membrane blebbing. Interacts with KLHL20 (PubMed:20389280). Interacts (via death domain) with MAPK1 and MAPK3 (PubMed:15616583). Interacts with MAP1B (via N-terminus) (PubMed:18195017). Interacts with PRKD1 in an oxidative stress-regulated manner (PubMed:17703233). Interacts with PIN1, PDCD6, BECN1, TSC2 and STX1A (PubMed:12730201, PubMed:16132846, PubMed:18974095, PubMed:19180116, PubMed:21497122). Interacts (via kinase domain) with DAPK3 (via kinase domain) (PubMed:15367680). Interacts with GRINB (By similarity). Interacts (via death domain) with UNC5B (via death domain) (PubMed:15729359). Interacts with UNC5C (via death domain) (PubMed:27068745).

6AAR
CRYSTAL STRUCTURE OF DAPK1 IN COMPLEX WITH PURPURIN
RCSB/PDB
Inspect Structure
See all 3D Structures for DAPK1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: DAPK1 is active in the following subcellular-locations: cytoplasm, cytoskeleton.
GO terms: DAPK1 is active in the following subcellular-locations: actin cytoskeleton, cytoplasm, nucleus, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project DAPK1 has gain in 0 cell-lines, loss in 1 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_OV_3, A498, A549

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: CaR-1, OVISE, MHH-ES-1

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, HUVEC, K562

(see details)

RNA Interference


DAPK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB453, T47D. (see details)

3D Structures


For DAPK1 there are:
55 structures (63 chains) solved
39 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


DAPK1 has been screened with 759 compounds (1366 bioactivities), 17 compounds have bioactivities that show binding affinity of <= 500nM (28 bioactivities). (see details)