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death associated protein kinase 1

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Target id: 2002

Nomenclature: death associated protein kinase 1

Abbreviated Name: DAPK1

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 - 1430 9q21.33 DAPK1 death associated protein kinase 1
Mouse - 1442 13 32.53 cM Dapk1 death associated protein kinase 1
Rat - 1430 17 p14 Dapk1 death associated protein kinase 1
Previous and Unofficial Names Click here for help
DAP-Kinase | DAP kinase 1 | death-associated protein kinase 1
Database Links Click here for help
Alphafold P53355 (Hs), Q80YE7 (Mm)
BRENDA 2.7.11.1
CATH/Gene3D 1.25.40.20
ChEMBL Target CHEMBL2558 (Hs)
Ensembl Gene ENSG00000196730 (Hs), ENSMUSG00000021559 (Mm), ENSRNOG00000018198 (Rn)
Entrez Gene 1612 (Hs), 69635 (Mm), 306722 (Rn)
Human Protein Atlas ENSG00000196730 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:1612 (Hs), mmu:69635 (Mm), rno:306722 (Rn)
OMIM 600831 (Hs)
Pharos P53355 (Hs)
RefSeq Nucleotide NM_004938 (Hs), NM_029653 (Mm), NM_001107335 (Rn)
RefSeq Protein NP_004929 (Hs), NP_083929 (Mm), NP_001100805 (Rn)
SynPHARM 81547 (in complex with staurosporine)
UniProtKB P53355 (Hs), Q80YE7 (Mm)
Wikipedia DAPK1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  1.5A X-RAY STRUCTURE OF APO FORM OF A CATALYTIC DOMAIN OF DEATH-ASSOCIATED PROTEIN KINASE
PDB Id:  1JKS
Resolution:  1.5Å
Species:  Human
References:  7
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of death associated protein kinase complexed with AMPPNP
PDB Id:  3EHA
Resolution:  1.6Å
Species:  Human
References:  6
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.3 pIC50 4
⤷ pIC50 9.3 (IC50 5x10-10 M) [4]
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: DAPK1
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.3 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.6 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
BI-2536 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 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: DAPK1/DAPK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.0 8.0 3.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.6 6.0 0.5
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 26.6 57.0 41.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 29.0 48.0 10.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 32.7 49.0 60.0
GSK-3 inhibitor XIII Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 39.1 59.0 17.0
STO609 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 40.9 79.0 47.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 47.7 75.0 31.0
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 66.9
GTP-14564 Small molecule or natural product Hs Inhibitor Inhibition 71.0 94.0 98.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling
Physiological Functions Click here for help
DAPK1 phosphorylates the peptidylprolyl cis/trans isomerase PIN1 at Ser71. This inhibits PIN1 isomerase activity.
Species:  Human
Tissue: 
References:  5

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. Hall MD, Salam NK, Hellawell JL, Fales HM, Kensler CB, Ludwig JA, Szakács G, Hibbs DE, Gottesman MM. (2009) Synthesis, activity, and pharmacophore development for isatin-beta-thiosemicarbazones with selective activity toward multidrug-resistant cells. J Med Chem, 52 (10): 3191-204. [PMID:19397322]

5. Kim BM, You MH, Chen CH, Lee S, Hong Y, Hong Y, Kimchi A, Zhou XZ, Lee TH. (2014) Death-associated protein kinase 1 has a critical role in aberrant tau protein regulation and function. Cell Death Dis, 5: e1237. [PMID:24853415]

6. McNamara LK, Watterson DM, Brunzelle JS. (2009) Structural insight into nucleotide recognition by human death-associated protein kinase. Acta Crystallogr D Biol Crystallogr, 65 (Pt 3): 241-8. [PMID:19237746]

7. Tereshko V, Teplova M, Brunzelle J, Watterson DM, Egli M. (2001) Crystal structures of the catalytic domain of human protein kinase associated with apoptosis and tumor suppression. Nat Struct Biol, 8 (10): 899-907. [PMID:11573098]

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 1. Last modified on 08/02/2022. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2002.