DAPK3

Summary

DAPK3 (death associated protein kinase 3, HGNC:2676) is a protein-coding gene on chromosome 19p13.3, encoding Death-associated protein kinase 3 (O43293). Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization.

Death-associated protein kinase 3 (DAPK3) induces morphological changes in apoptosis when overexpressed in mammalian cells. These results suggest that DAPK3 may play a role in the induction of apoptosis.

Source: NCBI Gene 1613 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 77 total
• Druggable target: yes — 29 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001348

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2676
Approved symbol	DAPK3
Name	death associated protein kinase 3
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	ZIP, ZIPK
Ensembl gene	ENSG00000167657
Ensembl biotype	protein_coding
OMIM	603289
Entrez	1613

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000301264, ENST00000545797, ENST00000593844, ENST00000594894, ENST00000595279, ENST00000596311, ENST00000601824, ENST00000875568, ENST00000954519, ENST00000954520

RefSeq mRNA: 2 — MANE Select: NM_001348 NM_001348, NM_001375658

CCDS: CCDS12116

Canonical transcript exons

ENST00000545797 — 9 exons

Exon	Start	End
ENSE00001115351	3961009	3961161
ENSE00001115354	3963643	3963669
ENSE00001115355	3963871	3963919
ENSE00001806720	3964244	3964373
ENSE00002223031	3970921	3971099
ENSE00002313591	3969674	3969829
ENSE00003052826	3958453	3959637
ENSE00003530523	3960059	3960104
ENSE00003787451	3964631	3964991

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 97.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1002 / max 96.6072, expressed in 1808 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178347	19.4268	1808
178346	0.6734	470

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.73	gold quality
mucosa of stomach	UBERON:0001199	97.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.11	gold quality
lower esophagus	UBERON:0013473	97.09	gold quality
popliteal artery	UBERON:0002250	96.91	gold quality
tibial artery	UBERON:0007610	96.91	gold quality
stromal cell of endometrium	CL:0002255	96.69	gold quality
ascending aorta	UBERON:0001496	96.69	gold quality
aorta	UBERON:0000947	96.67	gold quality
right atrium auricular region	UBERON:0006631	96.67	gold quality
thoracic aorta	UBERON:0001515	96.62	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.49	gold quality
body of uterus	UBERON:0009853	96.45	gold quality
gastrocnemius	UBERON:0001388	96.31	gold quality
right coronary artery	UBERON:0001625	96.30	gold quality
muscle of leg	UBERON:0001383	95.93	gold quality
descending thoracic aorta	UBERON:0002345	95.50	gold quality
left uterine tube	UBERON:0001303	95.30	gold quality
left coronary artery	UBERON:0001626	95.18	gold quality
heart left ventricle	UBERON:0002084	95.16	gold quality
ectocervix	UBERON:0012249	94.90	gold quality
cardiac ventricle	UBERON:0002082	94.64	gold quality
coronary artery	UBERON:0001621	94.61	gold quality
cardiac atrium	UBERON:0002081	94.51	gold quality
body of stomach	UBERON:0001161	94.22	gold quality
upper lobe of left lung	UBERON:0008952	94.21	gold quality
endocervix	UBERON:0000458	94.02	gold quality
heart	UBERON:0000948	93.67	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

11 targeting DAPK3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-647	97.73	67.79	927
HSA-MIR-6749-5P	89.28	58.87	75

Literature-anchored findings (GeneRIF, showing 38)

• These results suggest that ZIPK, in collaboration with Daxx and Par-4, mediates a novel nuclear pathway for apoptosis (PMID:12917339)
• data identify hZIPK as the unique SMPP-1-associated kinase expressed in human vesicular smooth muscle and support a role for Rho in promoting the hZIPK-MBS interaction (PMID:15292222)
• The specific expression pattern of TCP10L and interaction with DAPK-3 implies that TCP10L might play crucially important roles in spermatogenesis through its interaction with DAPK-3. (PMID:15910542)
• ZIP kinase plays a crucial role in androgen receptor-mediated transcription. (PMID:18084323)
• These results suggest that UbcH5 regulates ZIPK accumulation in PML-NBs by interacting with ZIPK and stimulating its ubiquitination. (PMID:18515077)
• ZIPK is a tumor suppresser gene and plays an important role in gastric carcinoma (PMID:19117059)
• Dlk plays a positive role in modulating death-related signaling pathways. (PMID:20085750)
• The NLS2 of human ZIPK functions the nucleus-directing motif, but only upon dephosphorylation of the adjacent T299 residue. (PMID:20854903)
• ZIPK may serve as a transcriptional regulator of canonical Wnt/beta-catenin signaling through interaction with NLK/TCF4. (PMID:21454679)
• Results suggest that DAPK3 is a tumor suppressor in which loss-of-function mutations promote increased cell survival, proliferation, cellular aggregation. (PMID:21487036)
• ZIPK has a crucial role in regulation of ubiquitination and degradation of the AR (PMID:23146908)
• Interaction of RhoD and ZIP kinase modulates actin filament assembly and focal adhesion dynamics. (PMID:23454120)
• Depletion of ZIPK resulted in impairment of cultured VSMC migration and contraction. (PMID:24633547)
• Cellular and mouse modeling studies show that DAPK3 is a tumor suppressor gene and is important in early development. Also, its expression is downregulated in more aggressive breast cancer relative to less aggressive and normal patient samples. (PMID:25304685)
• These findings indicated that ZIPK may also be involved in the regulation of the cell cycle in human cells, by interacting with HsCdc14A. (PMID:25503649)
• ROCK1 and ZIPK have diverse, but predominantly distinct regulatory functions in vascular SMC and that ROCK1-mediated activation of ZIPK is not involved in most of these functions. (PMID:25723491)
• findings suggest that ZIPK plays a role in the progression and completion of cytokinesis through MRLC phosphorylation (PMID:25769953)
• DAPK3 plays a central role in preventing miR-17/miR-20a depletion-induced genome instability and in miR-17/miR-20a overexpression-triggered tumor formation. (PMID:26117336)
• The results revealed mutations caused a significant structural variation in DAPK3, concentrated in flexible loops forming part of the ATP binding pocket which have been associated with very low kinase activity, and the cellular progression towards cancer (PMID:26748242)
• Activation of AKT negatively regulates the pro-apoptotic function of DAPK3 in prostate cancer. (PMID:27126362)
• Methylation of DAPK3 at CpG1 but not CpG2 was lower in men with type 2 diabetes compared with healthy control men. Moreover, a glucose challenge was associated with lower CpG1 and CpG2 methylation in DAPK3 in both men with type 2 diabetes and healthy men. (PMID:28011458)
• DAPK3 controls proliferation, migration and tumor growth through activation of ERK/c-Myc signaling in lung adenocarcinoma cells. (PMID:28075459)
• For the first time, the present study showed that anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway. (PMID:28731173)
• The initial characterization of tumor-suppressing kinases- in particular members of the protein kinase C (PKC) family, MKK4 of the mitogen-activated protein kinase kinase family, and DAPK3 of the death-associated protein kinase family- laid the foundation for bioinformatic approaches that enable the identification of other tumor-suppressing kinases. (PMID:30548122)
• Silencing DAPK3 blocks the autophagosome-lysosome fusion by mediating SNAP29 in trophoblast cells under high glucose treatment. (PMID:31811899)
• DAPK3 participates in the mRNA processing of immediate early genes in chronic lymphocytic leukaemia. (PMID:32306542)
• Loss of ZIP facilitates JAK2-STAT3 activation in tamoxifen-resistant breast cancer. (PMID:32532922)
• Impairment of cytokinesis by cancer-associated DAPK3 mutations. (PMID:33032825)
• The phosphorylation of hCDC14A modulated by ZIPK regulates autophagy of murine pancreatic islet beta-TC3 cells upon glucose stimulation. (PMID:33090408)
• The tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFN-beta pathway. (PMID:33767426)
• ZIPK activates the IL-6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells. (PMID:34375503)
• VIRMA contributes to non-small cell lung cancer progression via N(6)-methyladenosine-dependent DAPK3 post-transcriptional modification. (PMID:34520821)
• Sirt7 associates with ELK1 to participate in hyperglycemia memory and diabetic nephropathy via modulation of DAPK3 expression and endothelial inflammation. (PMID:35470010)
• Molecular Network Analyses Implicate Death-Associated Protein Kinase 3 (DAPK3) as a Key Factor in Colitis-Associated Dysplasia Progression. (PMID:35604388)
• Zipper interacting protein kinase (ZIPK) is a negative regulator of HIV-1 replication that is restricted by viral Nef protein through proteasomal degradation. (PMID:35961135)
• Death-associated protein kinase 3 regulates the myogenic reactivity of cerebral arteries. (PMID:37084168)
• YTHDF2 promotes gallbladder cancer progression and gemcitabine resistance via m6A-dependent DAPK3 degradation. (PMID:37700438)
• Inhibition of DAPK3 Suppresses Radiation-Induced Cellular Senescence by Activation of a PGC1alpha-Dependent Metabolism Pathway in Brain Endothelial Cells. (PMID:38563090)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dapk3	ENSDARG00000074447
mus_musculus	Dapk3	ENSMUSG00000034974
rattus_norvegicus	Dapk3	ENSRNOG00000020383

Paralogs (4): DAPK2 (ENSG00000035664), MYLK (ENSG00000065534), NEXN (ENSG00000162614), DAPK1 (ENSG00000196730)

Protein

Protein identifiers

Death-associated protein kinase 3 — O43293 (reviewed: O43293)

Alternative names: DAP-like kinase, MYPT1 kinase, Zipper-interacting protein kinase

All UniProt accessions (4): O43293, M0QYW5, M0QYY8, M0R0D0

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Subunit / interactions. Homooligomer in its kinase-active form (homotrimers and homodimers are reported); monomeric in its kinase-inactive form. Homodimerization is required for activation segment autophosphorylation. 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. Interacts with LUZP1; the interaction is likely to occur throughout the cell cycle and reduces the LUZP1-mediated suppression of MYL9 phosphorylation.

Subcellular location. Nucleus. PML body. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Chromosome. Centromere. Spindle. Midbody Nucleus. Cytoplasm Nucleus.

Tissue specificity. Widely expressed. Isoform 1 and isoform 2 are expressed in the bladder smooth muscle.

Post-translational modifications. The phosphorylation status is critical for kinase activity, oligomerization and intracellular localization. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. The phosphorylated form is localized in the cytoplasm promoted by phosphorylation at Thr-299; nuclear translocation or retention is maximal when it is not phosphorylated. Phosphorylation increases the trimeric form, and its dephosphorylation favors a kinase-inactive monomeric form. Both isoform 1 and isoform 2 can undergo autophosphorylation.

Activity regulation. A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain stabilized by phosphorylation at Ser-50 and activation segment exchange (producing an active confirmation of both kinase modules in trans) followed by phosphorylation at Thr-180 in the activation segment and at other regulatory sites. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Oligomerization is required for full enzymatic activity. Inhibited by pyridone-6 (K00225), a potent, ATP-competitive inhibitor.

Miscellaneous. The internal splice site between exon 8 and the 3’ UTR, which yields this truncated isoform, is non-canonical.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O43293-1	1, ZIPK-L	yes
O43293-2	2, ZIPK-S

RefSeq proteins (2): NP_001339, NP_001362587 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR042870	DAPK3_STKc	Domain

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (64 total): helix 17, mutagenesis site 12, modified residue 11, strand 9, binding site 4, sequence variant 3, region of interest 2, splice variant 2, chain 1, domain 1, active site 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
3BHY	X-RAY DIFFRACTION	1.24
5A6O	X-RAY DIFFRACTION	1.6
5A6N	X-RAY DIFFRACTION	1.7
3BQR	X-RAY DIFFRACTION	1.75
2J90	X-RAY DIFFRACTION	2
5VJA	X-RAY DIFFRACTION	2.46
1YRP	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43293-F1	87.22	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 139 (proton acceptor)

Ligand- & substrate-binding residues (4): 19–27; 42; 94; 96

Post-translational modifications (11): 180, 225, 265, 299, 306, 309, 311, 312, 318, 326, 50

Mutagenesis-validated functional residues (12):

Position	Phenotype
42	loss of kinase activity at low concentrations of atp.
161	loss of kinase activity.
180	greatly reduced kinase activity.
225	loss of kinase activity.
265	loss of phosphorylation by rock1, catalytically inactive.
294–295	cytoplasmic localization.
299–300	predominantly nuclear localization.
299	loss of phosphorylation by rock1.
299	predominantly cytoplasmic localization; phosphomimetic.
427	predominantly nuclear localization; when associated with a-434 and a-441.
434	predominantly nuclear localization; when associated with a-427 and a-441.
441	predominantly nuclear localization; when associated with a-427 and a-434.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418889	Caspase activation via Dependence Receptors in the absence of ligand

MSigDB gene sets: 197 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX

GO Biological Process (23): chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355), protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), regulation of smooth muscle contraction (GO:0006940), regulation of mitotic nuclear division (GO:0007088), regulation of mitotic cell cycle (GO:0007346), regulation of cell shape (GO:0008360), regulation of autophagy (GO:0010506), negative regulation of translation (GO:0017148), positive regulation of cell migration (GO:0030335), regulation of actin cytoskeleton organization (GO:0032956), intracellular signal transduction (GO:0035556), regulation of apoptotic process (GO:0042981), positive regulation of apoptotic process (GO:0043065), regulation of myosin II filament organization (GO:0043519), protein autophosphorylation (GO:0046777), regulation of focal adhesion assembly (GO:0051893), cellular response to type II interferon (GO:0071346), positive regulation of canonical Wnt signaling pathway (GO:0090263), apoptotic signaling pathway (GO:0097190), regulation of cell motility (GO:2000145), regulation of translation (GO:0006417)

GO Molecular Function (13): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), cAMP response element binding protein binding (GO:0008140), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), leucine zipper domain binding (GO:0043522), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (12): chromosome, centromeric region (GO:0000775), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), cilium (GO:0005929), PML body (GO:0016605), midbody (GO:0030496), chromosome (GO:0005694), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Caspase activation via extrinsic apoptotic signalling pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	3
intracellular anatomical structure	2
apoptotic process	2
protein kinase activity	2
cellular component organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
regulation of muscle contraction	1
smooth muscle contraction	1
regulation of mitotic cell cycle	1
regulation of cell cycle process	1
regulation of nuclear division	1
mitotic nuclear division	1
mitotic cell cycle	1
regulation of cell cycle	1
regulation of cell morphogenesis	1
regulation of biological quality	1
autophagy	1
regulation of catabolic process	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
signal transduction	1
regulation of programmed cell death	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1

Protein interactions and networks

STRING

2233 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAPK3	PAWR	Q96IZ0	876
DAPK3	CALML3	P27482	829
DAPK3	CALML5	Q9NZT1	829
DAPK3	CALML6	Q8TD86	818
DAPK3	CALML4	Q96GE6	818
DAPK3	AATF	Q9NY61	803
DAPK3	CALM1	P02593	761
DAPK3	PPP1R12A	O14974	745
DAPK3	BECN1	Q14457	736
DAPK3	DAXX	Q9UER7	623
DAPK3	DAP	P51397	573
DAPK3	PPP1R14A	Q96A00	571
DAPK3	UNC5B	Q8IZJ1	557
DAPK3	RHOD	O00212	553
DAPK3	PIK3C3	Q8NEB9	525

IntAct

101 interactions, top by confidence:

A	B	Type	Score
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
DAPK3	DAPK3	psi-mi:“MI:0407”(direct interaction)	0.680
DAPK3	DAPK3	psi-mi:“MI:0915”(physical association)	0.680
TCP10L	DAPK3	psi-mi:“MI:0915”(physical association)	0.670
DAPK3	LUZP1	psi-mi:“MI:0915”(physical association)	0.670
LUZP1	DAPK3	psi-mi:“MI:0914”(association)	0.670
DAPK3	TCP10L	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
DAPK3	PPP1R12A	psi-mi:“MI:0915”(physical association)	0.590
PPP1R12A	DAPK3	psi-mi:“MI:0915”(physical association)	0.590
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
CEP170	DAPK3	psi-mi:“MI:0914”(association)	0.530
GPS2	DCTN6	psi-mi:“MI:0914”(association)	0.530
KIF2B	BACH1	psi-mi:“MI:0914”(association)	0.530
TNFRSF8	DAPK3	psi-mi:“MI:0914”(association)	0.530
MYL12B	DAPK3	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (135): DAPK3 (Biochemical Activity), DAPK3 (Co-localization), DAPK3 (Co-localization), DAPK3 (Co-localization), AR (Co-localization), MDM2 (Co-localization), DAPK3 (Affinity Capture-Western), DAPK3 (Biochemical Activity), DAPK3 (Affinity Capture-MS), DAPK3 (Affinity Capture-MS), DAPK3 (Proximity Label-MS), DAPK3 (Proximity Label-MS), DAPK3 (Proximity Label-MS), DAPK3 (Proximity Label-MS), DAPK3 (Proximity Label-MS)

ESM2 similar proteins: A2XFF4, B8BBT7, D3ZHP7, O43293, O61661, O75676, P10665, P11275, P11730, P11798, P18652, P18653, P18654, P38935, P51812, P53684, P97343, Q13163, Q13555, Q13557, Q15349, Q15418, Q38997, Q3B7N1, Q3U3Q1, Q4V7Q6, Q5RCC4, Q5RCY1, Q5WA76, Q5ZJH6, Q60560, Q63285, Q63531, Q6DEH3, Q6PFQ0, Q6PHR2, Q6PHZ2, Q6Z2M9, Q7TPS0, Q852Q0

Diamond homologs: A0A509AFG4, A0A5K1K8H0, A2AAJ9, A2ZVI7, A4IFM7, A8C984, A8WXF6, B9FKW9, C0HKC8, C0HKC9, E9PT87, O02827, O43293, O44997, O54784, O62305, O70150, O75147, O80673, O88764, O94768, P07313, P08414, P11801, P13234, P15735, P18653, P20689, P29294, P31325, P34101, P43292, P53355, P53681, Q00168, Q00771, Q0KHT7, Q0V7M1, Q10KY3, Q14012

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
DAPK3	“up-regulates quantity by stabilization”	MDM2	phosphorylation
DAPK3	up-regulates	DAPK3	phosphorylation
DAPK3	up-regulates	TP53	phosphorylation
DAPK3	up-regulates	MYL12B	phosphorylation
DAPK3	up-regulates	RPL13A	phosphorylation
DAPK3	up-regulates	MYL9	phosphorylation
DAPK3	“down-regulates activity”	PPP1R12A	phosphorylation
ROCK1	“up-regulates activity”	DAPK3	phosphorylation
DAPK3	“up-regulates activity”	STAT3	phosphorylation
DAPK3	“up-regulates quantity by stabilization”	CDKN1A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	5	57.7×	1e-06
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	50.9×	2e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	50.9×	2e-06
RHO GTPases activate CIT	5	45.5×	3e-06
RHO GTPases activate PKNs	9	43.3×	2e-10
RHO GTPases activate PAKs	5	41.2×	4e-06
Activation of BH3-only proteins	5	37.6×	6e-06
Intrinsic Pathway for Apoptosis	6	26.6×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	27.8×	5e-05
cell division	9	5.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

77 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1164 predictions. Top by Δscore:

Variant	Effect	Δscore
19:3959633:ATCGC:A	acceptor_gain	1.0000
19:3959634:TCGC:T	acceptor_gain	1.0000
19:3959635:CGC:C	acceptor_gain	1.0000
19:3959635:CGCC:C	acceptor_gain	1.0000
19:3959636:GC:G	acceptor_gain	1.0000
19:3959637:CC:C	acceptor_gain	1.0000
19:3959637:CCTAG:C	acceptor_loss	1.0000
19:3959638:C:CC	acceptor_gain	1.0000
19:3959638:CTA:C	acceptor_loss	1.0000
19:3959639:T:G	acceptor_loss	1.0000
19:3961007:A:AC	donor_gain	1.0000
19:3961008:C:CA	donor_gain	1.0000
19:3961008:CT:C	donor_gain	1.0000
19:3961008:CTT:C	donor_gain	1.0000
19:3961008:CTTGG:C	donor_gain	1.0000
19:3961137:C:CT	acceptor_gain	1.0000
19:3961157:TCAGG:T	acceptor_gain	1.0000
19:3961158:CAGG:C	acceptor_gain	1.0000
19:3961158:CAGGC:C	acceptor_gain	1.0000
19:3961159:AGG:A	acceptor_gain	1.0000
19:3961160:GG:G	acceptor_gain	1.0000
19:3961162:C:CC	acceptor_gain	1.0000
19:3963641:A:AC	donor_gain	1.0000
19:3963642:C:CC	donor_gain	1.0000
19:3963670:C:CC	acceptor_gain	1.0000
19:3963863:ACACT:A	donor_loss	1.0000
19:3963864:CACTC:C	donor_loss	1.0000
19:3963865:ACTCA:A	donor_loss	1.0000
19:3963866:CTCA:C	donor_loss	1.0000
19:3963867:TCACC:T	donor_loss	1.0000

AlphaMissense

2976 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:3960065:C:A	W274C	1.000
19:3960065:C:G	W274C	1.000
19:3960067:A:G	W274R	1.000
19:3960067:A:T	W274R	1.000
19:3960098:T:A	R263S	1.000
19:3960098:T:G	R263S	1.000
19:3960099:C:G	R263T	1.000
19:3961024:A:G	L256P	1.000
19:3961027:A:G	L255P	1.000
19:3961039:A:G	F251S	1.000
19:3961048:G:T	A248D	1.000
19:3961140:G:C	F217L	1.000
19:3961140:G:T	F217L	1.000
19:3961141:A:G	F217S	1.000
19:3961142:A:G	F217L	1.000
19:3961142:A:T	F217I	1.000
19:3961144:G:T	P216Q	1.000
19:3961153:C:T	G213D	1.000
19:3961159:A:G	L211P	1.000
19:3963643:A:G	L210P	1.000
19:3963650:A:C	Y208D	1.000
19:3963661:C:A	G204V	1.000
19:3963661:C:T	G204D	1.000
19:3963662:C:G	G204R	1.000
19:3963669:C:A	W201C	1.000
19:3963669:C:G	W201C	1.000
19:3963872:A:G	W201R	1.000
19:3963872:A:T	W201R	1.000
19:3963878:C:A	D199Y	1.000
19:3963878:C:G	D199H	1.000

dbSNP variants (sampled 300 via entrez): RS1000269403 (19:3968851 C>T), RS1000905398 (19:3968726 G>A,T), RS1000932278 (19:3961250 A>G), RS1001007091 (19:3970022 CAA>C), RS1001037784 (19:3965381 T>C), RS1001090113 (19:3965214 G>A), RS1001346772 (19:3968916 G>C,T), RS1001365324 (19:3961854 CTTTAAATTT>C), RS1001378220 (19:3963745 C>A,G,T), RS1001425282 (19:3966278 T>C), RS1001427037 (19:3961106 T>C), RS1001670860 (19:3962058 C>T), RS1001682106 (19:3971266 T>A,C), RS1001948020 (19:3967793 T>A,C), RS1002018843 (19:3972223 G>A,C)

Disease associations

OMIM: gene MIM:603289 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001814_2	Age-related macular degeneration	6.000000e-06
GCST001814_7	Age-related macular degeneration	7.000000e-06
GCST002611_6	Expressive vocabulary in infants	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006316	infant expressive language ability

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2468 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

29 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 375,986 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL38380	FASUDIL	3	11,953
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980715	LAUROGUADINE	2	294
CHEMBL475251	R-406	2	762
CHEMBL513909	BI-2536	2	895
CHEMBL521851	PICTILISIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL607707	PELITINIB	2
CHEMBL1084546	PF-00562271	1
CHEMBL1908394	GSK-461364	1
CHEMBL1908397	KW-2449	1
CHEMBL482967	CYC-116	1
CHEMBL494089	GSK-690693	1
CHEMBL574738	AST-487	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Death-associated kinase (DAPK) family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
silmitasertib	Inhibition	7.77	pIC50
URMC-099	Inhibition	6.82	pIC50
DAPK inhibitor 13	Inhibition	6.6	pIC50

Binding affinities (BindingDB)

7 measured of 7 human assays (7 total across all organisms); most potent 7 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
GEFITINIB	IC50	2300 nM	US-9416123: Kinase modulators for the treatment of cancer
3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol	KD	2400 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

420 potent at pChembl≥5 of 456 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	1	nM	STAUROSPORINE
9.00	Ki	1	nM	CHEMBL21156
8.92	Kd	1.2	nM	FEDRATINIB
8.73	IC50	1.84	nM	STAUROSPORINE
8.70	Ki	1.995	nM	CHEMBL1980995
8.60	Ki	2.512	nM	CHEMBL474432
8.50	IC50	3.14	nM	STAUROSPORINE
8.46	IC50	3.45	nM	STAUROSPORINE
8.40	Ki	3.981	nM	CHEMBL1998159
8.30	Ki	5.012	nM	CHEMBL1980407
8.30	Ki	5.012	nM	CHEMBL1984548
8.10	Ki	7.943	nM	CHEMBL1980329
8.10	Ki	7.943	nM	CHEMBL2000345
8.10	Ki	7.943	nM	CHEMBL1999931
8.00	IC50	10	nM	CHEMBL3103192
7.90	Ki	12.59	nM	CHEMBL1980435
7.90	Ki	12.59	nM	CHEMBL1994669
7.90	Ki	12.59	nM	CHEMBL1998432
7.89	Kd	13	nM	CHEMBL4875028
7.89	Kd	13	nM	R-406
7.80	Ki	15.85	nM	CHEMBL1985723
7.80	Ki	15.85	nM	CHEMBL1970522
7.80	Ki	15.85	nM	CHEMBL2002613
7.80	Ki	15.85	nM	CHEMBL1994241
7.80	Ki	15.85	nM	CHEMBL1969523
7.77	IC50	17	nM	SILMITASERTIB
7.70	Ki	19.95	nM	CHEMBL1997129
7.70	Ki	19.95	nM	CHEMBL1964399
7.70	Ki	19.95	nM	CHEMBL2005475
7.70	Ki	19.95	nM	CHEMBL2001751
7.70	Ki	19.95	nM	CHEMBL1983923
7.66	Kd	22	nM	SUNITINIB
7.60	Kd	25	nM	CHEMBL4576489
7.60	Ki	25.12	nM	CHEMBL1987261
7.60	Ki	25.12	nM	CHEMBL2000354
7.60	Ki	25.12	nM	CHEMBL1966343
7.60	Ki	25.12	nM	CHEMBL226403
7.60	Ki	25.12	nM	CHEMBL1968930
7.60	Ki	25.12	nM	CHEMBL1999484
7.56	Ki	27.3	nM	CHEMBL523823
7.50	Ki	31.62	nM	CHEMBL1987034
7.50	Ki	31.62	nM	CHEMBL523823
7.50	Ki	31.62	nM	CHEMBL1975128
7.50	Ki	31.62	nM	CHEMBL1969537
7.50	Ki	31.62	nM	CHEMBL1996980
7.50	Ki	31.62	nM	CHEMBL1991078
7.50	Ki	31.62	nM	CHEMBL1975418
7.40	Ki	39.81	nM	CHEMBL1995813
7.40	Ki	39.81	nM	CHEMBL1973098
7.40	Ki	39.81	nM	CHEMBL1966808

PubChem BioAssay actives

101 with measured affinity, of 2004 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	256659: Average Binding Constant for DAPK3; NA=Not Active at 10 uM	kd	0.0010	uM
Fedratinib	624834: Binding constant for DAPK3 kinase domain	kd	0.0012	uM
N-[2-[2-aminoethyl(methyl)amino]-5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]acetamide	1301625: Inhibition of Dapk3 (unknown origin) at by quantitative PCR	ic50	0.0100	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624834: Binding constant for DAPK3 kinase domain	kd	0.0130	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]cyclohexanecarboxamide	1760721: Binding affinity to wild-type human partial length DAPK3 (M1 to A277 residues) expressed in bacterial expression system by measuring active site-directed competition binding based Kinomescan method	kd	0.0130	uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid	1705052: Inhibition of recombinant human DAPK3 in presence of ATP at Km concentration by radiometric filter-binding assay	ic50	0.0170	uM
Sunitinib	435398: Binding constant for DAPK3 kinase domain	kd	0.0220	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526295: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged DAPK3 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0250	uM
7-chloro-9-ethyl-6-hydroxy-1H-[1,2]oxazolo[3,4-b]quinoline-3,4-dione	387805: Inhibition of Zipk	ki	0.0273	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624834: Binding constant for DAPK3 kinase domain	kd	0.0410	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526295: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged DAPK3 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0410	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	391394: Inhibition of human DAPK3	ic50	0.0810	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507894: Binding affinity to DAPK3	kd	0.0820	uM
Ruxolitinib	624834: Binding constant for DAPK3 kinase domain	kd	0.0890	uM
2-[[1-(3-fluorophenyl)-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl]sulfanyl]butanamide	1966664: Inhibition of human recombinant GST-fused DAPK3 (1 to 320 residues) expressed in Escherichia coli BL21 (DE3) assessed as inhibition constant using MYPT1 as peptide substrate incubated for 10 mins in presence of [gamma-32P]ATP by radiometric scintillation assay	ki	0.1190	uM
2-methyl-2-[(4-oxo-1-phenyl-5H-pyrazolo[5,4-d]pyrimidin-6-yl)sulfanyl]propanamide	1966664: Inhibition of human recombinant GST-fused DAPK3 (1 to 320 residues) expressed in Escherichia coli BL21 (DE3) assessed as inhibition constant using MYPT1 as peptide substrate incubated for 10 mins in presence of [gamma-32P]ATP by radiometric scintillation assay	ki	0.1260	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	624834: Binding constant for DAPK3 kinase domain	kd	0.1300	uM
N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]cyclopropanecarboxamide	1298197: Inhibition of DAPK3 (unknown origin)	ic50	0.1400	uM
(4Z)-2-(3-bromophenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.1484	uM
(4Z)-2-(2-bromo-4-methoxyphenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.1570	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435398: Binding constant for DAPK3 kinase domain	kd	0.1700	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435155: Binding constant for full-length DLK	kd	0.1900	uM
(4Z)-2-(2-chloro-5-iodophenyl)-4-(pyridin-4-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.2271	uM
4-fluoro-2-methoxy-11-oxo-5-propan-2-yl-3-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]-6H-indolo[2,3-b]quinoline-8-carbonitrile	1700702: Inhibition of human DAPK3	ic50	0.2600	uM
2-[[1-(3-chlorophenyl)-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl]sulfanyl]propanamide	1966664: Inhibition of human recombinant GST-fused DAPK3 (1 to 320 residues) expressed in Escherichia coli BL21 (DE3) assessed as inhibition constant using MYPT1 as peptide substrate incubated for 10 mins in presence of [gamma-32P]ATP by radiometric scintillation assay	ki	0.2600	uM
(4Z)-2-(4-bromo-3-methylphenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.2785	uM
(4Z)-2-(4-chloro-3-nitrophenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.2785	uM
(4Z)-2-(4-nitrophenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.2912	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624834: Binding constant for DAPK3 kinase domain	kd	0.3100	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-methoxy-2-N-[4-(methylsulfonylmethyl)phenyl]pyrimidine-2,4-diamine	1966672: Inhibition of DAPK3 (unknown origin)	ic50	0.3100	uM
2-[[1-(3-chlorophenyl)-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl]sulfanyl]acetonitrile	1966664: Inhibition of human recombinant GST-fused DAPK3 (1 to 320 residues) expressed in Escherichia coli BL21 (DE3) assessed as inhibition constant using MYPT1 as peptide substrate incubated for 10 mins in presence of [gamma-32P]ATP by radiometric scintillation assay	ki	0.3150	uM
(4Z)-2-(3,4-difluorophenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.3461	uM
(4Z)-2-(3-chlorophenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.3596	uM
methyl (15R,16S,18S)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate	277639: Inhibition of DLK	ic50	0.3600	uM
(4Z)-2-(3-methoxyphenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.3953	uM
14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2,4,6,9(16),10,12-heptaen-8-one	256659: Average Binding Constant for DAPK3; NA=Not Active at 10 uM	kd	0.4100	uM
N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]-3-methylbut-2-enamide	1298197: Inhibition of DAPK3 (unknown origin)	ic50	0.4500	uM
3,13-diazahexacyclo[14.8.0.02,10.04,9.011,15.017,22]tetracosa-1(16),2(10),4,6,8,11(15),17,19,21-nonaene-12,14-dione	277639: Inhibition of DLK	ic50	0.4870	uM
N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]butanamide	1298197: Inhibition of DAPK3 (unknown origin)	ic50	0.5100	uM
(4Z)-2-(4-chlorophenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.5295	uM
(4Z)-2-(4-methyl-3-nitrophenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.5335	uM
2-methoxy-10-nitropyrido[3,4-g]quinazoline	1909355: Inhibition of human DAPK3 in presence of ATP by kinomescan assay	ic50	0.5780	uM
(4Z)-2-phenyl-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.5830	uM
N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]-2,2-dimethylpropanamide	1298197: Inhibition of DAPK3 (unknown origin)	ic50	0.7000	uM
(4Z)-2-(3-methylphenyl)-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	474761: Inhibition of human recombinant DAPK3	ic50	0.7137	uM
2-N-[(4-chloro-2-methoxyphenyl)methyl]-4-N-(5-ethyl-1H-pyrazol-3-yl)-5-methoxyquinazoline-2,4-diamine	1751885: Inhibition of recombinant human ZIPK (1 to 290 residues) using KKLNRTLSFAEPG substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay	ic50	0.7200	uM
3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenol	435398: Binding constant for DAPK3 kinase domain	kd	0.8400	uM
(4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone	769523: Binding affinity to DAPK3 (unknown origin)	kd	0.8800	uM
(4Z)-2-[(E)-2-phenylethenyl]-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one	443273: Inhibition of DAPK3	ic50	1.0000	uM
methyl N-[4-[5-[(2S)-2-amino-2,4-dimethylpentoxy]-6-chloro-2-pyridinyl]-2-pyridinyl]carbamate	1904672: Inhibition of DAPK3 (unknown origin)	ic50	1.1000	uM

CTD chemical–gene interactions

54 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, affects cotreatment, increases abundance, increases expression, affects expression (+1 more)	3
sodium arsenite	increases expression	2
Cisplatin	decreases expression, increases response to substance	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
lead acetate	increases expression	1
potassium perchlorate	decreases expression	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
motexafin gadolinium	affects reaction, increases expression, decreases expression	1
candoxin	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
abrine	increases expression	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	increases expression	1
Decitabine	increases expression	1
Leflunomide	increases expression	1

ChEMBL screening assays

281 unique, capped per target: 280 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011064	Binding	Inhibition of DAPK3 at 100 nM relative to control	Structural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases. — J Med Chem
CHEMBL1963719	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: DAPK3	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2VL	Abcam HEK293T DAPK3 KO	Transformed cell line	Female
CVCL_SK34	HAP1 DAPK3 (-) 1	Cancer cell line	Male
CVCL_SK35	HAP1 DAPK3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.