Browse DAPK1

Summary
SymbolDAPK1
Namedeath-associated protein kinase 1
Aliases DAPK; DAP kinase 1
Chromosomal Location9q34.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Isoform 1: Cytoplasm. Cytoplasm, cytoskeleton. Note=Colocalizes with MAP1B in the microtubules and cortical actin fibers.; SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. Cytoplasm, cytoskeleton.
Domain PF12796 Ankyrin repeats (3 copies)
PF00531 Death domain
PF00069 Protein kinase domain
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 deaths signal, 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. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.; FUNCTION: Isoform 2 cannot induce apoptosis but can induce membrane blebbing.

> Gene Ontology
 
Biological Process GO:0006417 regulation of translation
GO:0006914 autophagy
GO:0007215 glutamate receptor signaling pathway
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
GO:0010469 regulation of receptor activity
GO:0010506 regulation of autophagy
GO:0010608 posttranscriptional regulation of gene expression
GO:0010950 positive regulation of endopeptidase activity
GO:0010952 positive regulation of peptidase activity
GO:0017148 negative regulation of translation
GO:0022898 regulation of transmembrane transporter activity
GO:0032409 regulation of transporter activity
GO:0032412 regulation of ion transmembrane transporter activity
GO:0034248 regulation of cellular amide metabolic process
GO:0034249 negative regulation of cellular amide metabolic process
GO:0034341 response to interferon-gamma
GO:0034762 regulation of transmembrane transport
GO:0034765 regulation of ion transmembrane transport
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045862 positive regulation of proteolysis
GO:0046777 protein autophosphorylation
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0071346 cellular response to interferon-gamma
GO:0097191 extrinsic apoptotic signaling pathway
GO:0099601 regulation of neurotransmitter receptor activity
GO:1900449 regulation of glutamate receptor signaling pathway
GO:1902041 regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:2000116 regulation of cysteine-type endopeptidase activity
GO:2000310 regulation of N-methyl-D-aspartate selective glutamate receptor activity
GO:2001056 positive regulation of cysteine-type endopeptidase activity
GO:2001233 regulation of apoptotic signaling pathway
GO:2001234 negative regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
Molecular Function GO:0000149 SNARE binding
GO:0004674 protein serine/threonine kinase activity
GO:0004683 calmodulin-dependent protein kinase activity
GO:0005516 calmodulin binding
GO:0005525 GTP binding
GO:0017075 syntaxin-1 binding
GO:0019001 guanyl nucleotide binding
GO:0019905 syntaxin binding
GO:0032561 guanyl ribonucleotide binding
Cellular Component GO:0015629 actin cytoskeleton
> KEGG and Reactome Pathway
 
KEGG hsa04140 Regulation of autophagy
Reactome R-HSA-109581: Apoptosis
R-HSA-5357769: Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-418889: Ligand-independent caspase activation via DCC
R-HSA-5357801: Programmed Cell Death
Summary
SymbolDAPK1
Namedeath-associated protein kinase 1
Aliases DAPK; DAP kinase 1
Chromosomal Location9q34.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between DAPK1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.

Summary
SymbolDAPK1
Namedeath-associated protein kinase 1
Aliases DAPK; DAP kinase 1
Chromosomal Location9q34.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of DAPK1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolDAPK1
Namedeath-associated protein kinase 1
Aliases DAPK; DAP kinase 1
Chromosomal Location9q34.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of DAPK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0320.938
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.4480.767
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2770.82
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9161.0630.0331
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 591.2530.591
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.8240.784
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0270.941
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2090.901
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1720.927
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.4560.694
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.2250.457
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.360.0122
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of DAPK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.44.13.30.61
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.45.12.30.647
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.85.9-1.11
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.79.1-1.41
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolDAPK1
Namedeath-associated protein kinase 1
Aliases DAPK; DAP kinase 1
Chromosomal Location9q34.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DAPK1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolDAPK1
Namedeath-associated protein kinase 1
Aliases DAPK; DAP kinase 1
Chromosomal Location9q34.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DAPK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DAPK1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolDAPK1
Namedeath-associated protein kinase 1
Aliases DAPK; DAP kinase 1
Chromosomal Location9q34.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DAPK1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolDAPK1
Namedeath-associated protein kinase 1
Aliases DAPK; DAP kinase 1
Chromosomal Location9q34.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of DAPK1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolDAPK1
Namedeath-associated protein kinase 1
Aliases DAPK; DAP kinase 1
Chromosomal Location9q34.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between DAPK1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolDAPK1
Namedeath-associated protein kinase 1
Aliases DAPK; DAP kinase 1
Chromosomal Location9q34.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting DAPK1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting DAPK1.
ID Name Drug Type Targets #Targets
DB040695,6-Dihydro-Benzo[H]Cinnolin-3-YlamineSmall MoleculeDAPK11
DB04395Phosphoaminophosphonic Acid-Adenylate EsterSmall MoleculeACTA1, CCT3, CFTR, CSNK2A1, DAPK1, DTYMK, EPHA2, EPHB2, GALK1, GSK ......26
DB074446-(3-AMINOPROPYL)-4,9-DIMETHYLPYRROLO[3,4-C]CARBAZOLE-1,3(2H,6H)-DIONESmall MoleculeDAPK11