Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

DAPK3 (O43293) - Overview - Molecular Target Synopsis


DAPK3, Death-associated protein kinase 3
Enzyme Classification
UniProt O43293

Also Known as DAPK3_HUMAN, DAPK3, ZIPK

Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor. Homooligomer in its kinase-active form (homotrimers and homodimers are reported); monomeric in its kinase-inactive form. Homodimerization is required for activation segment autophosphorylation (Probable). Isoform 1 and isoform 2 interact with myosin and PPP1R12A; interaction of isoform 1 with PPP1R12A is inhibited by RhoA dominant negative form. Interacts with NLK, DAXX, STAT3, RHOD (GTP-bound form) and TCP10L. Interacts with PAWR; the interaction is reported conflictingly: according to PubMed:17953487 does not interact with PAWR. Interacts with ULK1; may be a substrate of ULK1.

Inspect Structure
See all 3D Structures for DAPK3

Isoforms / Transcripts (Protein Coding)

Sub-cellular localization

UniProt: DAPK3 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: DAPK3 is active in the following subcellular-locations: actin filament, cytoplasm, membrane raft, nucleus, PML body.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project DAPK3 has gain in 0 cell-lines, loss in 2 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: HS578T, LOXIMVI, SF_539

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: G61, SNU-423, G28T

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, IMR-90, HUVEC

(see details)

RNA Interference

DAPK3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SUM149, VP229. (see details)

3D Structures

For DAPK3 there are:
7 structures (14 chains) solved
5 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

DAPK3 has been screened with 490 compounds (885 bioactivities), 29 compounds have bioactivities that show binding affinity of <= 500nM (38 bioactivities). (see details)