DAPK2
gene geneOn this page
Also known as DRP-1MGC119312
Summary
DAPK2 (death associated protein kinase 2, HGNC:2675) is a protein-coding gene on chromosome 15q22.31, encoding Death-associated protein kinase 2 (Q9UIK4). Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy.
This gene encodes a protein that belongs to the serine/threonine protein kinase family. This protein contains a N-terminal protein kinase domain followed by a conserved calmodulin-binding domain with significant similarity to that of death-associated protein kinase 1 (DAPK1), a positive regulator of programmed cell death. Overexpression of this gene was shown to induce cell apoptosis. It uses multiple polyadenylation sites.
Source: NCBI Gene 23604 — RefSeq curated summary.
At a glance
- GWAS associations: 9
- Clinical variants (ClinVar): 86 total
- Druggable target: yes — 13 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_014326
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:2675 |
| Approved symbol | DAPK2 |
| Name | death associated protein kinase 2 |
| Location | 15q22.31 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | DRP-1, MGC119312 |
| Ensembl gene | ENSG00000035664 |
| Ensembl biotype | protein_coding |
| OMIM | 616567 |
| Entrez | 23604 |
Gene structure
Transcript identifiers
Ensembl transcripts: 17 — 9 protein_coding, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron
ENST00000261891, ENST00000457488, ENST00000557867, ENST00000558064, ENST00000558069, ENST00000558076, ENST00000558482, ENST00000559007, ENST00000559306, ENST00000559731, ENST00000559897, ENST00000561162, ENST00000612884, ENST00000908660, ENST00000908661, ENST00000943723, ENST00000943724
RefSeq mRNA: 20 — MANE Select: NM_014326
NM_001363730, NM_001384997, NM_001384998, NM_001384999, NM_001385000, NM_001395279, NM_001395281, NM_001395282, NM_001395283, NM_001395284, NM_001395285, NM_001395286, NM_001395287, NM_001395288, NM_001395289, NM_001395290, NM_001395291, NM_001395292, NM_001395293, NM_014326
CCDS: CCDS10188, CCDS86463
Canonical transcript exons
ENST00000457488 — 12 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001281614 | 63907036 | 63908600 |
| ENSE00003466541 | 63971423 | 63971561 |
| ENSE00003473652 | 64040170 | 64040267 |
| ENSE00003487172 | 63912108 | 63912197 |
| ENSE00003529418 | 63929551 | 63929577 |
| ENSE00003535596 | 63939232 | 63939361 |
| ENSE00003587735 | 63930407 | 63930455 |
| ENSE00003591892 | 63983533 | 63983754 |
| ENSE00003652942 | 63924816 | 63924861 |
| ENSE00003680892 | 63925941 | 63926093 |
| ENSE00003688429 | 63911908 | 63911991 |
| ENSE00003978112 | 64046298 | 64046485 |
Expression profiles
Bgee: expression breadth ubiquitous, 250 present calls, max score 96.74.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5947 / max 371.8702, expressed in 1025 samples.
FANTOM5 promoters (1 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 150447 | 3.5947 | 1025 |
Top tissues by expression
280 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| right lobe of thyroid gland | UBERON:0001119 | 96.74 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 95.73 | gold quality |
| right atrium auricular region | UBERON:0006631 | 95.28 | gold quality |
| thyroid gland | UBERON:0002046 | 95.14 | gold quality |
| right lung | UBERON:0002167 | 94.92 | gold quality |
| cardiac atrium | UBERON:0002081 | 94.72 | gold quality |
| gastrocnemius | UBERON:0001388 | 94.65 | gold quality |
| muscle of leg | UBERON:0001383 | 94.01 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 93.52 | gold quality |
| muscle organ | UBERON:0001630 | 91.51 | gold quality |
| type B pancreatic cell | CL:0000169 | 91.39 | gold quality |
| olfactory bulb | UBERON:0002264 | 91.25 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 91.25 | gold quality |
| heart left ventricle | UBERON:0002084 | 90.56 | gold quality |
| upper lobe of lung | UBERON:0008948 | 90.47 | gold quality |
| cardiac ventricle | UBERON:0002082 | 90.33 | gold quality |
| blood | UBERON:0000178 | 90.26 | gold quality |
| heart | UBERON:0000948 | 88.84 | gold quality |
| sural nerve | UBERON:0015488 | 88.81 | gold quality |
| apex of heart | UBERON:0002098 | 88.80 | gold quality |
| cardiac muscle of right atrium | UBERON:0003379 | 87.57 | gold quality |
| left ventricle myocardium | UBERON:0006566 | 87.53 | silver quality |
| duodenum | UBERON:0002114 | 87.36 | gold quality |
| hair follicle | UBERON:0002073 | 87.11 | gold quality |
| lung | UBERON:0002048 | 86.88 | gold quality |
| myocardium | UBERON:0002349 | 86.68 | gold quality |
| diaphragm | UBERON:0001103 | 86.48 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 86.27 | gold quality |
| buccal mucosa cell | CL:0002336 | 86.10 | silver quality |
| skeletal muscle tissue | UBERON:0001134 | 86.06 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 14.46 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): CEBPA, CTNNB1, E2F1, KLF6, RARA, SP1, SPI1, TCF7L2
miRNA regulators (miRDB)
59 targeting DAPK2, 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-7110-3P | 100.00 | 73.18 | 2486 |
| HSA-MIR-6873-3P | 100.00 | 71.42 | 2626 |
| HSA-MIR-4500 | 99.99 | 72.72 | 2367 |
| HSA-MIR-34A-5P | 99.99 | 71.21 | 1784 |
| HSA-MIR-449A | 99.99 | 71.05 | 1776 |
| HSA-MIR-4531 | 99.99 | 69.70 | 3181 |
| HSA-LET-7A-5P | 99.98 | 72.29 | 1790 |
| HSA-LET-7B-5P | 99.98 | 72.31 | 1790 |
| HSA-LET-7C-5P | 99.98 | 72.29 | 1790 |
| HSA-LET-7E-5P | 99.98 | 72.29 | 1790 |
| HSA-LET-7F-5P | 99.98 | 72.56 | 1784 |
| HSA-LET-7G-5P | 99.98 | 72.37 | 1784 |
| HSA-LET-7I-5P | 99.98 | 72.37 | 1788 |
| HSA-MIR-98-5P | 99.98 | 72.33 | 1787 |
| HSA-MIR-34C-5P | 99.97 | 70.45 | 1577 |
| HSA-MIR-449B-5P | 99.97 | 70.26 | 1580 |
| HSA-MIR-3605-5P | 99.96 | 67.12 | 932 |
| HSA-MIR-9983-3P | 99.94 | 71.48 | 3631 |
| HSA-MIR-515-5P | 99.92 | 69.82 | 2343 |
| HSA-MIR-519E-5P | 99.92 | 69.62 | 2358 |
| HSA-MIR-7162-3P | 99.89 | 68.16 | 1682 |
| HSA-MIR-12119 | 99.87 | 68.35 | 1653 |
| HSA-MIR-7978 | 99.86 | 66.90 | 856 |
| HSA-MIR-6817-3P | 99.79 | 68.35 | 2126 |
| HSA-MIR-3059-5P | 99.70 | 69.93 | 2491 |
| HSA-MIR-5093 | 99.67 | 69.26 | 2291 |
| HSA-MIR-4649-3P | 99.56 | 66.90 | 1783 |
| HSA-MIR-1252-3P | 99.55 | 67.71 | 2862 |
| HSA-MIR-519D-5P | 99.41 | 69.30 | 2057 |
| HSA-MIR-4687-5P | 99.14 | 66.26 | 488 |
Literature-anchored findings (GeneRIF, showing 27)
- High frequency of promoter hypermethylation of the death-associated protein-kinase gene in nasopharyngeal carcinoma and its detection in the peripheral blood of patients (PMID:11839660)
- distinct methylation pattern in bladder cancer with frequent methylation of RARbeta, DAPK, E-cadherin, and p16. (PMID:11839665)
- gene expression in colorectal and gastric cancer silenced by DNA methylation and histone deacetylation (PMID:12087472)
- Results implicate a novel role for DAPK2 in the regulation of normal myelopoiesis. (PMID:17347302)
- DAPK2 as a novel Sp1-dependent target gene for E2F1 and KLF6 in cell death response. (PMID:18521079)
- beta-catenin-induced down-regulation of DAPk-2 represents a novel signaling mechanism by which beta-catenin promotes the survival of malignant epithelial cells (PMID:18957423)
- Results showed that the inactivation of RASSF1A, RARbeta2 and DAP-Kinase by hypermethylation is a key step in NPC tumorigenesis and progression. (PMID:19221469)
- DRP-1 and ZIPk most likely evolved from their ancient ancestor gene DAPk by two gene duplication events that occurred close to the emergence of vertebrates (PMID:21408167)
- Sodium butyrate induced DAPK1/2 expression in human gastric cancer cells and this expression prompted apoptosis by decreasing FAK levels. (PMID:22160140)
- DAPK2 is upregulated in uterosacral ligaments in pelvic organ prolapse (PMID:23700042)
- The tumor suppressor gene DAPK2 is induced by the myeloid transcription factors PU.1 and C/EBPalpha during granulocytic differentiation but repressed by PML-RARalpha in APL. (PMID:24038216)
- The defect in chemotaxis in DAPK2-inactive granulocytes is likely a result of reduced polarization of the cells, mediated by a lack of MLC phosphorylation, resulting in radial F-actin and pseudopod formation. (PMID:24163421)
- DAPK2 is a novel kinase of mTORC1 and is a potential new member of this multiprotein complex, modulating mTORC1 activity and autophagy levels under stress and steady-state conditions. (PMID:25361081)
- DAPK2 regulates oxidative stress in cancer cells by preserving mitochondrial function (PMID:25741596)
- miR-520h suppresses Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. (PMID:25982274)
- This study links adipocyte expression of an autophagy-regulating kinase, lysosome-mediated clearance and fat cell lipid accumulation; it demonstrates obesity-related attenuated autophagy in adipocytes, and identifies DAPK2 dependence in this regulation. (PMID:26038578)
- DAPK2-induced apoptosis is negatively regulated by Akt and 14-3-3 proteins. (PMID:26047703)
- that Death-associated protein kinase 2 effector functions are influenced by the protein’s subcellular localization (PMID:26483415)
- This study suggests that miR-520g contributes to tumor progression and drug resistance by post-transcriptionally downregulating DAPK2 in patients with epithelial ovarian cancer (PMID:27049921)
- Thyroid hormone promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protects hepatocytes from diethylnitrosamine-induced hepatotoxicity or carcinogenesis. (PMID:27653365)
- study reveals a unique calmodulin-independent mechanism for DAPK2 activation, critical to its function as a novel downstream effector of AMPK in autophagy (PMID:29717115)
- remission effect of DAPK2 on placental cell oxidative damage and apoptosis in HDCP via mTOR activation (PMID:30243997)
- The intracellular signaling pathways that lead to Ser289 phosphorylation are mutually-exclusive and different for each kinase. In addition, Ser289 phosphorylation in fact enhances DAPK1 catalytic activity, similar to the effect on DAPK2. Thus, Ser289 phosphorylation activates both DAPK1 and DAPK2, but in response to different intracellular signaling pathways. (PMID:31116076)
- miR-1285-3p Controls Colorectal Cancer Proliferation and Escape from Apoptosis through DAPK2. (PMID:32244500)
- Cigarette smoking induces aberrant N(6)-methyladenosine of DAPK2 to promote non-small cell lung cancer progression by activating NF-kappaB pathway. (PMID:34298122)
- 14-3-3 proteins inactivate DAPK2 by promoting its dimerization and protecting key regulatory phosphosites. (PMID:34413451)
- Exosomal miR-133a-3p Derived from BMSCs Alleviates Cerebral Ischemia-Reperfusion Injury via Targeting DAPK2. (PMID:36636640)
Cross-species orthologs
4 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | dapk2a | ENSDARG00000061096 |
| danio_rerio | dapk2b | ENSDARG00000103666 |
| mus_musculus | Dapk2 | ENSMUSG00000032380 |
| rattus_norvegicus | Dapk2 | ENSRNOG00000017332 |
Paralogs (4): MYLK (ENSG00000065534), NEXN (ENSG00000162614), DAPK3 (ENSG00000167657), DAPK1 (ENSG00000196730)
Protein
Protein identifiers
Death-associated protein kinase 2 — Q9UIK4 (reviewed: Q9UIK4)
Alternative names: DAP-kinase-related protein 1
All UniProt accessions (5): Q9UIK4, H0YKW8, H0YL86, H0YLP5, H0YMK1
UniProt curated annotations — full annotation on UniProt →
Function. 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 death signals, 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. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation. Regulates granulocytic motility by controlling cell spreading and polarization. Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death.
Subunit / interactions. Homodimer in its autoinhibited state. Active as monomer. Isoform 2 but not isoform 1 can interact with ATF4. Interacts with 14-3-3 proteins YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN; the interaction requires DAPK2 phosphorylation at Thr-369 and suppresses DAPK2 kinase activity and DAPK2-induced apoptosis.
Subcellular location. Cytoplasm. Cytoplasmic vesicle. Autophagosome lumen.
Tissue specificity. Expressed in neutrophils and eosinophils. Isoform 2 is expressed in embryonic stem cells (at protein level). Isoform 1 is ubiquitously expressed in all tissue types examined with high levels in heart, lung and skeletal muscle.
Post-translational modifications. Autophosphorylation at Ser-318 inhibits its catalytic activity. Dephosphorylated at Ser-318 in response to activated Fas and TNF receptors.
Activity regulation. Activated by Ca(2+)/calmodulin. Regulated by a double locking mechanism, involving autophosphorylation at Ser-318, calmodulin binding, and dimerization. In the inactive state, Ser-318 is phosphorylated, and the kinase is dimeric. Activation involves: dephosphorylation at Ser-318, release-of-autoinhibition mechanism where calmodulin binding induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain, and generation of the monomeric active form of the kinase.
Domain organisation. The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core.
Induction. Up-regulated during granulocytic maturation.
Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q9UIK4-1 | 1, Alpha | yes |
| Q9UIK4-2 | 2, Beta |
RefSeq proteins (20): NP_001350659, NP_001371926, NP_001371927, NP_001371928, NP_001371929, NP_001382208, NP_001382210, NP_001382211, NP_001382212, NP_001382213, NP_001382214, NP_001382215, NP_001382216, NP_001382217, NP_001382218, NP_001382219, NP_001382220, NP_001382221, NP_001382222, NP_055141* (*=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 |
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 (60 total): helix 15, mutagenesis site 12, strand 11, modified residue 4, region of interest 4, turn 3, sequence variant 2, sequence conflict 2, binding site 2, chain 1, domain 1, splice variant 1, compositionally biased region 1, active site 1
Structure
Experimental structures (PDB)
11 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 2A2A | X-RAY DIFFRACTION | 1.47 |
| 1ZUZ | X-RAY DIFFRACTION | 1.91 |
| 1WRZ | X-RAY DIFFRACTION | 2 |
| 7A6Y | X-RAY DIFFRACTION | 2.5 |
| 7A6R | X-RAY DIFFRACTION | 2.7 |
| 2CKE | X-RAY DIFFRACTION | 2.8 |
| 1ZWS | X-RAY DIFFRACTION | 2.9 |
| 6PAW | X-RAY DIFFRACTION | 2.95 |
| 2A27 | X-RAY DIFFRACTION | 3 |
| 1WMK | X-RAY DIFFRACTION | 3.6 |
| 1Z9X | X-RAY DIFFRACTION | 3.93 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9UIK4-F1 | 86.41 | 0.74 |
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): 149 (proton acceptor)
Ligand- & substrate-binding residues (2): 29–37; 52
Post-translational modifications (4): 318, 349, 369, 299
Mutagenesis-validated functional residues (12):
| Position | Phenotype |
|---|---|
| 52 | loss of activity, apoptotic function and of autophosphorylation. |
| 299–330 | loss of ca(2+)-calmodulin binding, increase in activity, loss of autophosphorylation. |
| 299 | no effect on ca(2+)-calmodulin independent phosphorylation or apoptotic activity. |
| 318 | loss of ca(2+)-calmodulin independent phosphorylation, increase in apoptotic activity. |
| 318 | abolishes apoptotic activity. |
| 320 | no effect on ca(2+)-calmodulin independent phosphorylation or apoptotic activity. |
| 323 | no effect on ca(2+)-calmodulin independent phosphorylation or apoptotic activity. |
| 329 | no effect on ca(2+)-calmodulin independent phosphorylation or apoptotic activity. |
| 367 | no effect on interaction with ywhae. |
| 368 | no effect on interaction with ywhae. |
| 369 | interaction with ywhae is reduced. |
| 370 | interaction with ywhae is increased. |
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: 244 (showing top):
MORF_RAGE, GOBP_REGULATION_OF_AUTOPHAGY, MORF_FLT1, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, MODULE_45, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MORF_ESR1, MODULE_16, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_LEUKOCYTE_CHEMOTAXIS, MODULE_118
GO Biological Process (12): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), regulation of autophagy (GO:0010506), intracellular signal transduction (GO:0035556), regulation of apoptotic process (GO:0042981), positive regulation of apoptotic process (GO:0043065), anoikis (GO:0043276), protein autophosphorylation (GO:0046777), positive regulation of neutrophil chemotaxis (GO:0090023), neutrophil migration (GO:1990266), positive regulation of eosinophil chemotaxis (GO:2000424), regulation of intrinsic apoptotic signaling pathway (GO:2001242)
GO Molecular Function (10): protein serine/threonine kinase activity (GO:0004674), calmodulin binding (GO:0005516), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)
GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytoplasmic vesicle (GO:0031410), autophagosome lumen (GO:0034423), membrane (GO:0016020)
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 |
|---|---|
| apoptotic process | 3 |
| intracellular anatomical structure | 2 |
| positive regulation of granulocyte chemotaxis | 2 |
| protein kinase activity | 2 |
| protein binding | 2 |
| intracellular membrane-bounded organelle | 2 |
| cellular anatomical structure | 2 |
| cytoplasm | 2 |
| phosphorylation | 1 |
| protein modification process | 1 |
| programmed cell death | 1 |
| apoptotic signaling pathway | 1 |
| execution phase of apoptosis | 1 |
| autophagy | 1 |
| regulation of catabolic process | 1 |
| signal transduction | 1 |
| regulation of programmed cell death | 1 |
| regulation of apoptotic process | 1 |
| positive regulation of programmed cell death | 1 |
| protein phosphorylation | 1 |
| neutrophil chemotaxis | 1 |
| regulation of neutrophil chemotaxis | 1 |
| positive regulation of neutrophil migration | 1 |
| granulocyte migration | 1 |
| eosinophil chemotaxis | 1 |
| positive regulation of eosinophil migration | 1 |
| regulation of eosinophil chemotaxis | 1 |
| intrinsic apoptotic signaling pathway | 1 |
| regulation of intracellular signal transduction | 1 |
| regulation of apoptotic signaling pathway | 1 |
| adenyl ribonucleotide binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
| nucleoside phosphate binding | 1 |
| heterocyclic compound binding | 1 |
| kinase activity | 1 |
| phosphotransferase activity, alcohol group as acceptor | 1 |
| catalytic activity, acting on a protein | 1 |
| binding | 1 |
| transferase activity, transferring phosphorus-containing groups | 1 |
| catalytic activity | 1 |
Protein interactions and networks
STRING
1761 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| DAPK2 | CALML3 | P27482 | 825 |
| DAPK2 | CALML5 | Q9NZT1 | 825 |
| DAPK2 | CALML6 | Q8TD86 | 813 |
| DAPK2 | CALML4 | Q96GE6 | 813 |
| DAPK2 | CALM1 | P02593 | 740 |
| DAPK2 | BECN1 | Q14457 | 736 |
| DAPK2 | ATG14 | Q6ZNE5 | 620 |
| DAPK2 | UNC5B | Q8IZJ1 | 573 |
| DAPK2 | VMP1 | Q96GC9 | 529 |
| DAPK2 | MGMT | P16455 | 510 |
| DAPK2 | IFNG | P01579 | 507 |
| DAPK2 | RASSF1 | Q9NS23 | 507 |
| DAPK2 | PIK3C3 | Q8NEB9 | 503 |
| DAPK2 | TMEM74 | Q96NL1 | 496 |
| DAPK2 | MIB1 | Q86YT6 | 486 |
| DAPK2 | MAP1LC3C | Q9BXW4 | 486 |
IntAct
21 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| DAPK2 | FAM9B | psi-mi:“MI:0915”(physical association) | 0.670 |
| DAPK2 | DAPK2 | psi-mi:“MI:0915”(physical association) | 0.590 |
| CCDC91 | DAPK2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| DAPK2 | YWHAE | psi-mi:“MI:0915”(physical association) | 0.400 |
| SFN | DAPK2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| Bub1 | PEX10 | psi-mi:“MI:0914”(association) | 0.350 |
| RACGAP1 | STX18 | psi-mi:“MI:0914”(association) | 0.350 |
| LLGL2 | RBBP6 | psi-mi:“MI:0914”(association) | 0.350 |
| TUBGCP5 | DNAJC6 | psi-mi:“MI:0914”(association) | 0.350 |
| KLC3 | KLC1 | psi-mi:“MI:0914”(association) | 0.350 |
| SLK | ENSA | psi-mi:“MI:0914”(association) | 0.350 |
| DAPK2 | CCDC91 | psi-mi:“MI:0915”(physical association) | 0.000 |
BioGRID (20): DAPK2 (Biochemical Activity), FAM9B (Two-hybrid), DAPK2 (Affinity Capture-MS), DAPK2 (Affinity Capture-MS), DAPK2 (Affinity Capture-MS), DAPK2 (Affinity Capture-MS), DAPK2 (Affinity Capture-MS), TP73 (Affinity Capture-Western), ATG5 (Affinity Capture-Western), CCDC91 (Two-hybrid), DAPK2 (Proximity Label-MS), DAPK2 (Affinity Capture-MS), DAPK2 (Affinity Capture-MS), DAPK2 (Affinity Capture-Western), DAPK2 (Affinity Capture-MS)
ESM2 similar proteins: A8X6H4, O70150, O75582, P10665, P11275, P11798, P18652, P18653, P18654, P28583, P51812, Q13557, Q14012, Q15349, Q2HJF7, Q38869, Q38871, Q38872, Q39016, Q42396, Q54CY9, Q54SJ5, Q5F3L1, Q5R4K3, Q5RCC4, Q5ZKI0, Q63450, Q63531, Q6DEH3, Q6GLS4, Q6P2M8, Q6PFQ0, Q6PHZ2, Q7TPS0, Q869W6, Q8BW96, Q8IU85, Q8RWL2, Q8VDF3, Q91YS8
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
2 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| DAPK2 | “down-regulates activity” | DAPK2 | phosphorylation |
| DAPK2 | “down-regulates activity” | RPTOR | phosphorylation |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 16 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 |
|---|---|---|---|
| Membrane Trafficking | 6 | 18.5× | 3e-05 |
| Vesicle-mediated transport | 6 | 17.4× | 3e-05 |
| Signaling by Rho GTPases | 5 | 14.2× | 5e-04 |
| Signaling by Rho GTPases, Miro GTPases and RHOBTB3 | 5 | 13.9× | 5e-04 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
86 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 61 |
| Likely benign | 2 |
| Benign | 3 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
3007 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 15:63911900:TTAC:T | donor_loss | 1.0000 |
| 15:63911903:CCCA:C | donor_gain | 1.0000 |
| 15:63911905:CA:C | donor_loss | 1.0000 |
| 15:63911906:A:C | donor_loss | 1.0000 |
| 15:63911987:GAAAG:G | acceptor_gain | 1.0000 |
| 15:63911988:AAAG:A | acceptor_gain | 1.0000 |
| 15:63911989:AAG:A | acceptor_gain | 1.0000 |
| 15:63911990:AG:A | acceptor_gain | 1.0000 |
| 15:63911992:C:CC | acceptor_gain | 1.0000 |
| 15:63912002:C:CT | acceptor_gain | 1.0000 |
| 15:63912128:A:AC | donor_gain | 1.0000 |
| 15:63912129:C:CC | donor_gain | 1.0000 |
| 15:63912134:T:TA | donor_gain | 1.0000 |
| 15:63939376:G:GC | acceptor_gain | 1.0000 |
| 15:63968923:A:T | acceptor_gain | 1.0000 |
| 15:63983529:TCACA:T | donor_loss | 1.0000 |
| 15:63983530:CA:C | donor_loss | 1.0000 |
| 15:63983531:A:AC | donor_gain | 1.0000 |
| 15:63983531:AC:A | donor_loss | 1.0000 |
| 15:63983531:ACAG:A | donor_gain | 1.0000 |
| 15:63983532:C:CA | donor_gain | 1.0000 |
| 15:63983532:CA:C | donor_gain | 1.0000 |
| 15:63983532:CAG:C | donor_gain | 1.0000 |
| 15:63983532:CAGC:C | donor_gain | 1.0000 |
| 15:63983532:CAGCT:C | donor_gain | 1.0000 |
| 15:63983750:GGCCA:G | acceptor_gain | 1.0000 |
| 15:63983751:GCCA:G | acceptor_gain | 1.0000 |
| 15:63983751:GCCAC:G | acceptor_gain | 1.0000 |
| 15:63983752:CCA:C | acceptor_gain | 1.0000 |
| 15:63983752:CCAC:C | acceptor_gain | 1.0000 |
AlphaMissense
2472 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 15:63924824:A:G | W284R | 1.000 |
| 15:63924824:A:T | W284R | 1.000 |
| 15:63929569:C:T | G214D | 1.000 |
| 15:63930408:A:G | W211R | 1.000 |
| 15:63930408:A:T | W211R | 1.000 |
| 15:63939236:A:C | F193L | 1.000 |
| 15:63939236:A:T | F193L | 1.000 |
| 15:63939238:A:G | F193L | 1.000 |
| 15:63939249:C:T | G189E | 1.000 |
| 15:63939291:G:T | A175D | 1.000 |
| 15:63939302:G:C | D171E | 1.000 |
| 15:63939302:G:T | D171E | 1.000 |
| 15:63939303:T:A | D171V | 1.000 |
| 15:63939303:T:C | D171G | 1.000 |
| 15:63939303:T:G | D171A | 1.000 |
| 15:63939304:C:G | D171H | 1.000 |
| 15:63939353:G:C | N154K | 1.000 |
| 15:63939353:G:T | N154K | 1.000 |
| 15:63971423:C:A | K151N | 1.000 |
| 15:63971423:C:G | K151N | 1.000 |
| 15:63971427:A:G | L150P | 1.000 |
| 15:63971430:T:A | D149V | 1.000 |
| 15:63971470:C:A | G136W | 1.000 |
| 15:63983691:C:A | K52N | 1.000 |
| 15:63983691:C:G | K52N | 1.000 |
| 15:63983745:A:C | F34L | 1.000 |
| 15:63983745:A:T | F34L | 1.000 |
| 15:63983747:A:G | F34L | 1.000 |
| 15:63924822:C:A | W284C | 0.999 |
| 15:63924822:C:G | W284C | 0.999 |
dbSNP variants (sampled 300 via entrez): RS1000107348 (15:63935552 C>T), RS1000145543 (15:63918191 C>A,G,T), RS1000151449 (15:63926045 C>T), RS1000159768 (15:63957927 G>A), RS1000168350 (15:64032856 T>C), RS1000186708 (15:63999802 G>A), RS1000199066 (15:64022736 T>C), RS1000209320 (15:63954313 T>C), RS1000223287 (15:63937992 A>G), RS1000257474 (15:64028669 T>C), RS1000259669 (15:63971369 G>A), RS1000284577 (15:64010962 G>A), RS1000286353 (15:64045314 T>A), RS1000311443 (15:63965235 G>A,C), RS1000331546 (15:63923744 A>G)
Disease associations
OMIM: gene MIM:616567 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
9 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST004068_48 | Venous thromboembolism adjusted for sickle cell variant rs77121243-T | 3.000000e-06 |
| GCST004490_24 | Cerebrospinal fluid t-tau:AB1-42 ratio | 3.000000e-08 |
| GCST004616_62 | Platelet distribution width | 6.000000e-10 |
| GCST006904_4 | Cerebral amyloid deposition (PET imaging) | 1.000000e-06 |
| GCST008403_12 | Arterial stiffness index | 1.000000e-06 |
| GCST009507_6 | Triglyceride levels | 1.000000e-07 |
| GCST010242_40 | HDL cholesterol levels | 4.000000e-15 |
| GCST010250_2 | Systolic blood pressure x dichotomous lifestyle risk score interaction (2df test) | 3.000000e-06 |
| GCST010251_1 | Systolic blood pressure x dichotomous lifestyle risk score interaction (1df test) | 5.000000e-07 |
EFO canonical traits (8, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0007708 | t-tau:beta-amyloid 1-42 ratio measurement |
| EFO:0007984 | platelet component distribution width |
| EFO:0007707 | cerebral amyloid deposition measurement |
| EFO:0004517 | arterial stiffness measurement |
| EFO:0004530 | triglyceride measurement |
| EFO:0004612 | high density lipoprotein cholesterol measurement |
| EFO:0006335 | systolic blood pressure |
| EFO:0010724 | lifestyle measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL3123 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 116,167 (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 |
| CHEMBL502835 | NINTEDANIB | 4 | 8,545 |
| CHEMBL535 | SUNITINIB | 4 | 79,020 |
| CHEMBL608533 | MIDOSTAURIN | 4 | 7,259 |
| CHEMBL603469 | LESTAURTINIB | 3 | |
| CHEMBL91829 | RUBOXISTAURIN | 3 | 77 |
| CHEMBL1721885 | SU-014813 | 2 | 363 |
| CHEMBL475251 | R-406 | 2 | 762 |
| CHEMBL513909 | BI-2536 | 2 | 895 |
| CHEMBL1908394 | GSK-461364 | 1 | 1,093 |
| CHEMBL1908397 | KW-2449 | 1 | 622 |
| CHEMBL259084 | MLN-8054 | 1 | 2,430 |
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
Binding affinities (BindingDB)
5 measured of 5 human assays (5 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value |
|---|---|---|
| Staurosporine | KD | 1.7 nM |
| PKC-412 | KD | 190 nM |
| 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
53 potent at pChembl≥5 of 55 total, top 44 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 8.80 | Kd | 1.6 | nM | STAUROSPORINE |
| 8.52 | Kd | 3 | nM | STAUROSPORINE |
| 8.28 | IC50 | 5.21 | nM | STAUROSPORINE |
| 8.26 | IC50 | 5.56 | nM | STAUROSPORINE |
| 8.14 | IC50 | 7.25 | nM | STAUROSPORINE |
| 8.00 | IC50 | 10 | nM | CHEMBL3103192 |
| 7.66 | IC50 | 22 | nM | CHEMBL4764610 |
| 7.54 | Kd | 29 | nM | FEDRATINIB |
| 7.47 | Kd | 34 | nM | CHEMBL4465866 |
| 7.22 | Kd | 60 | nM | CHEMBL4576489 |
| 7.21 | Kd | 62 | nM | R-406 |
| 7.20 | Kd | 63 | nM | LESTAURTINIB |
| 7.10 | Kd | 79 | nM | CHEMBL5303531 |
| 7.03 | Kd | 94 | nM | CHEMBL1241674 |
| 7.01 | Kd | 97 | nM | RUXOLITINIB |
| 6.82 | Kd | 150 | nM | SUNITINIB |
| 6.77 | IC50 | 170 | nM | CHEMBL3799389 |
| 6.40 | Kd | 400 | nM | SU-014813 |
| 6.35 | Kd | 450 | nM | CHEMBL3921246 |
| 6.33 | Kd | 470 | nM | SUNITINIB |
| 6.24 | IC50 | 570 | nM | CHEMBL3797466 |
| 6.23 | IC50 | 590 | nM | CHEMBL3799585 |
| 6.21 | Kd | 610 | nM | SP-600125 |
| 6.08 | IC50 | 830 | nM | CHEMBL513703 |
| 6.06 | Kd | 870 | nM | TAE-684 |
| 6.05 | Kd | 890 | nM | MIDOSTAURIN |
| 6.03 | Kd | 930 | nM | BI-2536 |
| 6.00 | IC50 | 1000 | nM | TP-030-1 |
| 6.00 | IC50 | 1000 | nM | TP-030-2 |
| 6.00 | IC50 | 1000 | nM | TP-030n |
| 5.96 | Kd | 1100 | nM | CHEMBL464552 |
| 5.89 | Kd | 1300 | nM | CHEMBL2425628 |
| 5.75 | Kd | 1800 | nM | KW-2449 |
| 5.64 | IC50 | 2300 | nM | CHEMBL3797480 |
| 5.60 | IC50 | 2512 | nM | CHEMBL5549980 |
| 5.60 | Kd | 2500 | nM | CHEMBL379218 |
| 5.58 | Kd | 2600 | nM | RUBOXISTAURIN |
| 5.57 | Kd | 2700 | nM | PI-103 |
| 5.54 | Kd | 2900 | nM | GSK-461364 |
| 5.51 | IC50 | 3070 | nM | SULFURETIN |
| 5.50 | Kd | 3200 | nM | NINTEDANIB |
| 5.47 | Kd | 3400 | nM | CHEMBL1908395 |
| 5.20 | IC50 | 6340 | nM | CHEMBL4087337 |
| 5.04 | Kd | 9100 | nM | MLN-8054 |
PubChem BioAssay actives
50 with measured affinity, of 663 total; 36 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 | 435153: Binding constant for full-length DAPK2 | kd | 0.0016 | uM |
| N-[2-[2-aminoethyl(methyl)amino]-5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]acetamide | 1301624: Inhibition of Dapk2 (unknown origin) by quantitative PCR | ic50 | 0.0100 | 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 | 1700701: Inhibition of human DAPK2 | ic50 | 0.0220 | uM |
| Fedratinib | 625077: Binding constant for DAPK2 kinase domain | kd | 0.0290 | 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 | 1526172: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged DAPK2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay | kd | 0.0340 | 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 | 1526172: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged DAPK2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay | kd | 0.0600 | 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 | 625077: Binding constant for DAPK2 kinase domain | kd | 0.0620 | 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 | 507893: Binding affinity to DAPK2 | kd | 0.0630 | uM |
| 2-[[1-(3-chlorophenyl)-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl]sulfanyl]propanamide | 1966660: Binding affinity to DAPK2 (unknown origin) assessed as dissociation constant | kd | 0.0790 | uM |
| 2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol | 625077: Binding constant for DAPK2 kinase domain | kd | 0.0940 | uM |
| Ruxolitinib | 625077: Binding constant for DAPK2 kinase domain | kd | 0.0970 | uM |
| Sunitinib | 435153: Binding constant for full-length DAPK2 | kd | 0.1500 | uM |
| N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]cyclopropanecarboxamide | 1298196: Inhibition of DAPK2 (unknown origin) | ic50 | 0.1700 | 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 | 435153: Binding constant for full-length DAPK2 | kd | 0.4000 | uM |
| 6-[[4-[(Z)-[2-(4-ethylphenyl)imino-3-methyl-4-oxo-1,3-thiazolidin-5-ylidene]methyl]-2-pyridinyl]amino]pyridine-3-carboxylic acid | 1323334: Binding affinity to human DAPK2 expressed in Escherichia coli BL21 cells incubated for 1 hr by active site directed binding competition assay | kd | 0.4500 | uM |
| N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]-3-methylbut-2-enamide | 1298196: Inhibition of DAPK2 (unknown origin) | ic50 | 0.5700 | uM |
| N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]butanamide | 1298196: Inhibition of DAPK2 (unknown origin) | ic50 | 0.5900 | uM |
| 14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2,4,6,9(16),10,12-heptaen-8-one | 256651: Average Binding Constant for DAPK2; NA=Not Active at 10 uM | kd | 0.6100 | uM |
| N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]-2,2-dimethylpropanamide | 1298196: Inhibition of DAPK2 (unknown origin) | ic50 | 0.8300 | uM |
| 5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine | 625077: Binding constant for DAPK2 kinase domain | kd | 0.8700 | uM |
| Midostaurin | 435153: Binding constant for full-length DAPK2 | kd | 0.8900 | uM |
| 4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide | 625077: Binding constant for DAPK2 kinase domain | kd | 0.9300 | uM |
| 2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide | 625077: Binding constant for DAPK2 kinase domain | kd | 1.1000 | uM |
| (4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone | 769524: Binding affinity to DAPK2 (unknown origin) | kd | 1.3000 | uM |
| [4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone | 625077: Binding constant for DAPK2 kinase domain | kd | 1.8000 | uM |
| N-[2-hydroxy-3-(3-nitroso-1H-indol-2-yl)-1H-indol-5-yl]pentanamide | 1298196: Inhibition of DAPK2 (unknown origin) | ic50 | 2.3000 | uM |
| (2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine | 625077: Binding constant for DAPK2 kinase domain | kd | 2.5000 | uM |
| 5-[4-[2-aminoethyl(ethyl)amino]-3-(1,2,4-triazol-4-yl)anilino]-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile | 2066655: Inhibition of human DAPK2 expressed in HEK293 cells incubated for 2 hrs by NanoBRET assay | ic50 | 2.5119 | uM |
| (18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione | 256651: Average Binding Constant for DAPK2; NA=Not Active at 10 uM | kd | 2.6000 | 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 | 435153: Binding constant for full-length DAPK2 | kd | 2.7000 | uM |
| 5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide | 625077: Binding constant for DAPK2 kinase domain | kd | 2.9000 | uM |
| (2Z)-2-[(3,4-dihydroxyphenyl)methylidene]-6-hydroxy-1-benzofuran-3-one | 1446697: Inhibition of human DAPK2 | ic50 | 3.0700 | uM |
| methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate | 625077: Binding constant for DAPK2 kinase domain | kd | 3.2000 | uM |
| 5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride | 625077: Binding constant for DAPK2 kinase domain | kd | 3.4000 | uM |
| (2Z)-2-[(3,4-dihydroxyphenyl)methylidene]-5-methoxy-1-benzofuran-3-one | 1446697: Inhibition of human DAPK2 | ic50 | 6.3400 | uM |
| 4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid | 625077: Binding constant for DAPK2 kinase domain | kd | 9.1000 | uM |
CTD chemical–gene interactions
42 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Tretinoin | affects binding, affects reaction, increases reaction, increases expression | 4 |
| sodium arsenite | decreases expression, affects cotreatment, increases abundance | 3 |
| Estradiol | increases expression, increases reaction | 3 |
| Valproic Acid | affects cotreatment, decreases expression, increases methylation | 3 |
| Aflatoxin B1 | decreases expression, decreases methylation | 3 |
| Particulate Matter | increases abundance, decreases expression | 2 |
| aristolochic acid I | increases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| lead acetate | decreases expression | 1 |
| trichostatin A | increases expression | 1 |
| perfluorooctanoic acid | increases expression | 1 |
| benzo(e)pyrene | increases methylation | 1 |
| aflatoxin B2 | decreases methylation | 1 |
| cupric chloride | decreases expression | 1 |
| bafilomycin A | affects reaction, increases expression, increases reaction | 1 |
| tamibarotene | increases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| usnic acid | increases expression | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | affects cotreatment, decreases expression | 1 |
| cacalol | increases expression | 1 |
| dorsomorphin | decreases expression, affects cotreatment | 1 |
| jinfukang | affects cotreatment, decreases expression | 1 |
| Bortezomib | decreases expression, increases response to substance | 1 |
| Decitabine | increases expression | 1 |
| Sunitinib | increases expression | 1 |
| Arsenic Trioxide | increases cleavage, increases expression, affects reaction | 1 |
| Vorinostat | affects cotreatment, decreases expression | 1 |
| Air Pollutants | decreases expression, increases abundance | 1 |
| Amiodarone | increases expression | 1 |
| Arsenic | affects cotreatment, decreases expression, increases abundance | 1 |
ChEMBL screening assays
185 unique, capped per target: 185 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1034094 | Binding | Inhibition of DAPK2 at 3 uM | Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem |
Cellosaurus cell lines
1 cell lines: 1 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_SK33 | HAP1 DAPK2 (-) | Cancer cell line | Male |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.