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death associated protein kinase 2

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2003

Nomenclature: death associated protein kinase 2

Abbreviated Name: DAPK2

Family: Death-associated kinase (DAPK) family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 370 15q22.31 DAPK2 death associated protein kinase 2 6
Mouse - 370 9 35.75 cM Dapk2 death-associated protein kinase 2 6
Rat - 215 8 q24 Dapk2 death-associated protein kinase 2
Previous and Unofficial Names Click here for help
DRP-1 | death-associated protein kinase 2
Database Links Click here for help
Alphafold Q9UIK4 (Hs), Q8VDF3 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL3123 (Hs)
Ensembl Gene ENSG00000035664 (Hs), ENSMUSG00000032380 (Mm), ENSRNOG00000017332 (Rn)
Entrez Gene 23604 (Hs), 13143 (Mm), 300799 (Rn)
Human Protein Atlas ENSG00000035664 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:23604 (Hs), mmu:13143 (Mm), rno:300799 (Rn)
Pharos Q9UIK4 (Hs)
RefSeq Nucleotide NM_014326 (Hs), NM_010019 (Mm), NM_001013109 (Rn)
RefSeq Protein NP_055141 (Hs), NP_034149 (Mm), NP_001013127 (Rn)
UniProtKB Q9UIK4 (Hs), Q8VDF3 (Mm)
Wikipedia DAPK2 (Hs)
Enzyme Reaction Click here for help
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 Click here for help
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 Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.8 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand 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 Click here for help
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.1 2.5 0.0
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 18.0 11.0 14.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 39.4 54.0 20.0
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 43.8 9.0 -1.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 59.2 12.0 -3.0
GSK-3 inhibitor X Small molecule or natural product Hs Inhibitor Inhibition 68.7 86.0 65.0
GTP-14564 Small molecule or natural product Hs Inhibitor Inhibition 71.2 101.0 105.0
H-89 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 72.1 94.0 77.0
PDGF RTK inhibitor Small molecule or natural product Hs Inhibitor Inhibition 78.7 99.0 99.0
ERK inhibitor III Small molecule or natural product 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
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Tissue Distribution Click here for help
Bone marrow, heart, lung and skeletal muscle
Species:  Human
Technique:  Northern blot
References:  6
Physiological Functions Click here for help
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 07/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2003.