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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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DAPK2
death associated protein kinase 2
Chromosome 15 · 15q22.31
NCBI Gene: 23604Ensembl: ENSG00000035664.12HGNC: HGNC:2675UniProt: Q1RMF4
51PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of intrinsic apoptotic signaling pathwayidentical protein bindingprotein phosphorylationintracellular signal transductionneurodegenerative diseasealcohol drinkingeye diseaseneoplasm
✦AI Summary

DAPK2 (death-associated protein kinase 2) functions as a tumor suppressor kinase that regulates multiple cellular processes including apoptosis, autophagy, and immune responses 1. The protein acts through diverse mechanisms, with one isoform capable of phosphorylating MYL9 and inducing membrane blebbing and autophagic cell death in a calmodulin-independent manner. DAPK2 plays a critical role in activating autophagy through interactions with AMPK, mTORC1, and p73, while also inducing apoptotic pathways via p73 family and JNK interactions 1. Recent studies reveal DAPK2's importance in mitochondrial metabolism and cancer progression, where dysfunction leads to Mic60 lactylation and mitochondrial cristae remodeling, promoting EGFR-TKI resistance and metastasis in lung cancer 2. Additionally, DAPK2 shows connections to immune regulation, as related family member DAPK1 activity is inhibited by fumarate accumulation in CD8+ T cells, affecting anti-tumor immunity 3. The kinase demonstrates tumor suppressor functions across various cancers including gastric, ovarian, and breast cancers, making it a potential therapeutic target 1. DAPK2's multifaceted roles in cell death pathways, metabolic regulation, and immune responses highlight its significance in cancer biology and therapeutic development.

Sources cited
1
DAPK2 acts as tumor suppressor, interacts with AMPK/mTORC1/p73 for autophagy, induces apoptosis via p73/JNK, and affects various cancers
PMID: 39105958
2
DAPK2 dysfunction leads to Mic60 lactylation, mitochondrial cristae remodeling, and promotes EGFR-TKI resistance and metastasis in lung cancer
PMID: 40812308
3
Related DAPK1 activity is inhibited by fumarate in CD8+ T cells, affecting anti-tumor immunity
PMID: 39151423
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.49Moderate
alcohol drinkingOpen Targets
0.37Weak
eye diseaseOpen Targets
0.23Weak
neoplasmOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
Alzheimer diseaseOpen Targets
0.10Weak
lung cancerOpen Targets
0.10Weak
SepsisOpen Targets
0.10Weak
ovarian cancerOpen Targets
0.10Weak
Huntington diseaseOpen Targets
0.10Suggestive
esophageal squamous cell carcinomaOpen Targets
0.10Suggestive
cancerOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.09Suggestive
triple-negative breast cancerOpen Targets
0.09Suggestive
nasopharyngeal carcinomaOpen Targets
0.09Suggestive
chronic kidney diseaseOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.08Suggestive
non-alcoholic steatohepatitisOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CALML4Protein interaction100%CALML5Protein interaction100%CALML3Protein interaction100%CALML6Protein interaction100%MAPK3Protein interaction99%CALM2Protein interaction99%
Tissue Expression6 tissues
Lung
100%
Heart
71%
Bone Marrow
28%
Brain
12%
Liver
6%
Ovary
3%
Gene Interaction Network
Click a node to explore
DAPK2CALML4CALML5CALML3CALML6MAPK3CALM2
PROTEIN STRUCTURE
Preparing viewer…
PDB2A2A · 1.47 Å · X-ray
View on RCSB ↗
RankingsWhere DAPK2 stands among ~20K protein-coding genes
  • #8,662of 20,598
    Most Researched51
Genes detectedDAPK2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Mitochondrial fragmentation limits NK cell-based tumor immunosurveillance.
PMID: 31636463
Nat Immunol · 2019
1.00
2
The tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFN-β pathway.
PMID: 33767426
Nat Immunol · 2021
0.90
3
Malic enzyme 2 maintains metabolic state and anti-tumor immunity of CD8
PMID: 39151423
Mol Cell · 2024
0.80
4
Dapk2 dysfunction leads to Mic60 lactylation and mitochondrial metabolic reprogramming, promoting lung cancer EGFR-TKI resistance and metastasis.
PMID: 40812308
Dev Cell · 2025
0.70
5
Structural basis of mitochondrial receptor binding and constriction by DRP1.
PMID: 29899447
Nature · 2018
0.60