DAPK1 (Death-Associated Protein Kinase 1)
A calcium/calmodulin-dependent serine/threonine kinase involved in apoptosis, autophagy, and tumor suppression.
Gene Information Card
| Symbol | DAPK1 |
|---|---|
| Full Name | Death Associated Protein Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q21.33 |
| NCBI Gene ID | 1612 ncbi.nlm.nih.gov/gene/1612 |
| Ensembl ID | ENSG00000196730 |
| UniProt ID | P53355 |
| OMIM ID | 600831 |
| HGNC ID | 2674 |
| Aliases | DAPK, DKFZp781I0355 |
Description
DAPK1 encodes a calcium/calmodulin-dependent serine/threonine kinase that functions as a positive mediator of apoptosis. It is involved in multiple cellular processes including autophagy, cell migration, and cytoskeletal reorganization. DAPK1 acts as a tumor suppressor and its expression is frequently silenced by promoter methylation in various cancers. It also plays roles in neuronal cell death and neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Promoter hypermethylation silences DAPK1 expression, reducing apoptosis and promoting tumorigenesis. | ClinVar, COSMIC, NCBI |
| Alzheimer's disease | DAPK1 phosphorylates tau protein, contributing to neurofibrillary tangle formation. | OMIM, NCBI |
| Stroke/ischemic brain injury | DAPK1 mediates excitotoxic neuronal death via interaction with NMDA receptors. | NCBI, UniProt |
| Lung cancer | Frequent methylation of DAPK1 promoter associated with poor prognosis. | COSMIC, ClinVar |
| Bladder cancer | DAPK1 methylation correlates with tumor progression and recurrence. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
| Spleen | 4.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.2 | Embryonic kidney |
| HeLa | 7.8 | Cervical carcinoma |
| A549 | 5.4 | Lung carcinoma |
| SH-SY5Y | 14.1 | Neuroblastoma |
| MCF7 | 3.9 | Breast carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Loss of start codon; likely loss of function |
| c.1129C>T (p.Arg377Trp) | Missense | <0.1% | Kinase domain; reduced catalytic activity |
| c.2146G>A (p.Gly716Arg) | Missense | <0.1% | C-terminal domain; unknown significance |
| Promoter methylation | Epigenetic | Frequent in tumors | Silences gene expression; loss of tumor suppressor function |
Mutation functional classification
Loss of Function (LOF)
Promoter methylation and missense mutations in the kinase domain (e.g., p.Arg377Trp) reduce or abolish DAPK1 kinase activity and pro-apoptotic function.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in DAPK1.
Dominant Negative (DN)
No dominant-negative mutations have been described for DAPK1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Apoptosis – intrinsic pathway
• p53 signaling pathway
• Autophagy – regulation
• TNF signaling pathway
• Neurotrophin signaling pathway
Protein Summary
DAPK1 is a 160 kDa calcium/calmodulin-dependent serine/threonine kinase. It contains an N-terminal kinase domain, a calmodulin-binding regulatory domain, ankyrin repeats, a cytoskeleton-binding region, and a death domain. The protein is ubiquitously expressed with highest levels in brain and testis. DAPK1 promotes apoptosis by phosphorylating substrates such as myosin light chain, Beclin-1, and tau. Its tumor suppressor role is often inactivated by promoter hypermethylation in cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DAPK1 Knockout HEK293 Cell Line | EDJ-KQ3701 | Human | 1612 | Details Get a Quote |
| DAPK1 Knockout A-549 Cell Line | EDJ-KQ24343 | Human | 1612 | Details Get a Quote |
| DAPK1 Knockout HCT 116 Cell Line | EDJ-KQ25716 | Human | 1612 | Details Get a Quote |
| DAPK1 Knockout HeLa Cell Line | EDJ-KQ25717 | Human | 1612 | Details Get a Quote |
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