death associated protein kinase 2 | Death-associated kinase (DAPK) family | IUPHAR/BPS Guide to PHARMACOLOGY

death associated protein kinase 2

Target id: 2003

Nomenclature: death associated protein kinase 2

Abbreviated Name: DAPK2

Family: Death-associated kinase (DAPK) family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     death associated protein kinase 2 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 370 15q22.1 DAPK2 death associated protein kinase 2 6
Mouse - 370 9 C Dapk2 death-associated protein kinase 2 6
Rat - 215 8 q24 Dapk2 death-associated protein kinase 2
Previous and Unofficial Names
DRP-1 | death-associated protein kinase 2
Database Links
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.11.1
Inhibitor Comments
DAPK inhibitor 13 is a pan-DAPK inhibitor in enzyme activity assays [5,7].
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 2,8

Key to terms and symbols Click column headers to sort
Target used in screen: DAPK2
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 8.8 pKd
fedratinib Hs Inhibitor Inhibition 7.5 pKd
tamatinib Hs Inhibitor Inhibition 7.2 pKd
lestaurtinib Hs Inhibitor Inhibition 7.2 pKd
PP-242 Hs Inhibitor Inhibition 7.0 pKd
ruxolitinib Hs Inhibitor Inhibition 7.0 pKd
sunitinib Hs Inhibitor Inhibition 6.8 pKd
SU-14813 Hs Inhibitor Inhibition 6.4 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.1 pKd
midostaurin Hs Inhibitor Inhibition 6.1 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: 1,3

Key to terms and symbols Click column headers to sort
Target used in screen: DAPK2/DAPK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 4.1 2.5 0.0
JAK inhibitor I Hs Inhibitor Inhibition 18.0 11.0 14.0
SB 218078 Hs Inhibitor Inhibition 39.4 54.0 20.0
isogranulatimide Hs Inhibitor Inhibition 43.8 9.0 -1.0
K-252a Hs Inhibitor Inhibition 59.2 12.0 -3.0
GSK-3 inhibitor X Hs Inhibitor Inhibition 68.7 86.0 65.0
GTP-14564 Hs Inhibitor Inhibition 71.2 101.0 105.0
H-89 Hs Inhibitor Inhibition 72.1 94.0 77.0
PDGF RTK inhibitor Hs Inhibitor Inhibition 78.7 99.0 99.0
ERK inhibitor III Hs Inhibitor Inhibition 80.1 93.0 109.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
DAPk2 is recognised as a regulator of apoptosis, autophagy and inflammation [4]. DAPK2 may be a novel target for anti-inflammatory therapies due to its involvement in positively recruiting neutrophils sites of inflammation.
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   granulocyte (CL:0000094)
Comment:  DAPK2 is the prevailing DAPK family member in granulocytes.
References:  5
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 3 GO processes
GO:0090023 positive regulation of neutrophil chemotaxis IMP
GO:2000424 positive regulation of eosinophil chemotaxis IMP
click arrow to show/hide IEA associations
GO:1990266 neutrophil migration IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0090023 positive regulation of neutrophil chemotaxis IMP
GO:2000424 positive regulation of eosinophil chemotaxis IMP
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 3 GO processes
GO:0090023 positive regulation of neutrophil chemotaxis IMP
GO:2000424 positive regulation of eosinophil chemotaxis IMP
click arrow to show/hide IEA associations
GO:1990266 neutrophil migration IEA
Tissue Distribution
Bone marrow, heart, lung and skeletal muscle
Species:  Human
Technique:  Northern blot
References:  6
Physiological Functions
Phosphorylates myosin light chain as an exogenous substrate; proapoptotic
Species:  Human
Tissue:  In vitro
References:  6
DAPK2 positively regulates motility of granulocytes in response to intermediary but not end-target chemoattractants ex vivo.
Species:  Human
Tissue:  Isolated human leukocytes
References:  5
General Comments
DAPK2 is a cytoplasmic Ca2+/CaM-dependent protein kinase and activity is modulated by intracellular Ca2+-concentration. Overexpression of DAPK2 induces morphological changes indicative of apoptosis [6].

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1039-45. [PMID:22037377]

2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]

3. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J., 451 (2): 313-28. [PMID:23398362]

4. Geering B. (2015) Death-associated protein kinase 2: Regulator of apoptosis, autophagy and inflammation. Int. J. Biochem. Cell Biol., 65: 151-4. [PMID:26055515]

5. Geering B, Stoeckle C, Rozman S, Oberson K, Benarafa C, Simon HU. (2014) DAPK2 positively regulates motility of neutrophils and eosinophils in response to intermediary chemoattractants. J. Leukoc. Biol., 95 (2): 293-303. [PMID:24163421]

6. Kawai T, Nomura F, Hoshino K, Copeland NG, Gilbert DJ, Jenkins NA, Akira S. (1999) Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity. Oncogene, 18 (23): 3471-80. [PMID:10376525]

7. Okamoto M, Takayama K, Shimizu T, Muroya A, Furuya T. (2010) Structure-activity relationship of novel DAPK inhibitors identified by structure-based virtual screening. Bioorg. Med. Chem., 18 (7): 2728-34. [PMID:20206532]

8. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol., 17 (11): 1241-9. [PMID:21095574]

How to cite this page

Death-associated kinase (DAPK) family: death associated protein kinase 2. Last modified on 19/01/2017. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2003.