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dual specificity tyrosine phosphorylation regulated kinase 2

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Target id: 2011

Nomenclature: dual specificity tyrosine phosphorylation regulated kinase 2

Abbreviated Name: DYRK2

Family: Dyrk2 subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 601 12q15 DYRK2 dual specificity tyrosine phosphorylation regulated kinase 2
Mouse - 599 10 D2 Dyrk2 dual-specificity tyrosine phosphorylation regulated kinase 2
Rat - 527 7 q22 Dyrk2 dual specificity tyrosine phosphorylation regulated kinase 2
Previous and Unofficial Names Click here for help
dual specificity tyrosine-(Y)-phosphorylation regulated kinase 2
Database Links Click here for help
Alphafold Q92630 (Hs), Q5U4C9 (Mm)
BRENDA 2.7.12.1
ChEMBL Target CHEMBL4376 (Hs)
Ensembl Gene ENSG00000127334 (Hs), ENSMUSG00000028630 (Mm), ENSRNOG00000007821 (Rn)
Entrez Gene 8445 (Hs), 69181 (Mm), 314862 (Rn)
Human Protein Atlas ENSG00000127334 (Hs)
KEGG Enzyme 2.7.12.1
KEGG Gene hsa:8445 (Hs), mmu:69181 (Mm), rno:314862 (Rn)
OMIM 603496 (Hs)
Pharos Q92630 (Hs)
RefSeq Nucleotide NM_003583 (Hs), NM_001014390 (Mm), NM_001108100 (Rn)
RefSeq Protein NP_003574 (Hs), NP_001014412 (Mm), NP_001101570 (Rn)
UniProtKB Q92630 (Hs), Q5U4C9 (Mm)
Wikipedia DYRK2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of dual-specificity tyrosine phosphorylation regulated kinase 2 (DYRK2) in complex with an indirubin ligand
PDB Id:  3KVW
Resolution:  2.28Å
Species:  Human
References: 
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of dual-specificity tyrosine phosphorylation regulated kinase 2 (DYRK2)
PDB Id:  3K2L
Resolution:  2.36Å
Species:  Human
References:  7
Enzyme Reaction Click here for help
EC Number: 2.7.12.1

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
leucettine L41 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.5 pIC50 4
⤷ pIC50 9.5 (IC50 3.5x10-10 M) [4]
compound 5b [PMID: 24900464] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 5
⤷ pIC50 7.2 (IC50 6x10-8 M) [5]
compound 3b [PMID: 23454515] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.9 pIC50 2
⤷ pIC50 6.9 (IC50 1.3x10-7 M) [2]
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: 3,8
Key to terms and symbols Click column headers to sort
Target used in screen: DYRK2
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.7 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 5.9 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: 1,6
Key to terms and symbols Click column headers to sort
Target used in screen: DYRK2/DYRK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 3.1 -5.0 -6.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 5.9 91.0 58.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 9.9 2.0 -4.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 12.1 1.0 -5.0
SP600125 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 14.2 4.0 -5.0
Cdc2-like kinase inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 19.5 5.0 -5.0
JNK inhibitor V Small molecule or natural product Hs Inhibitor Inhibition 22.2 19.0 2.0
PI 3-Kg inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 39.8 7.0 -4.0
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 46.8 28.0 12.0
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 47.0 52.0 7.0
Displaying the top 10 most potent ligands  View all ligands in screen »

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. Burgy G, Tahtouh T, Durieu E, Foll-Josselin B, Limanton E, Meijer L, Carreaux F, Bazureau JP. (2013) Chemical synthesis and biological validation of immobilized protein kinase inhibitory Leucettines. Eur J Med Chem, 62: 728-37. [PMID:23454515]

3. 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]

4. Debdab M, Carreaux F, Renault S, Soundararajan M, Fedorov O, Filippakopoulos P, Lozach O, Babault L, Tahtouh T, Baratte B et al.. (2011) Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. J Med Chem, 54 (12): 4172-86. [PMID:21615147]

5. Dowling JE, Chuaqui C, Pontz TW, Lyne PD, Larsen NA, Block MH, Chen H, Su N, Wu A, Russell D et al.. (2012) Potent and Selective Inhibitors of CK2 Kinase Identified through Structure-Guided Hybridization. ACS Med Chem Lett, 3 (4): 278-83. [PMID:24900464]

6. 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]

7. Soundararajan M, Roos AK, Savitsky P, Filippakopoulos P, Kettenbach AN, Olsen JV, Gerber SA, Eswaran J, Knapp S, Elkins JM. (2013) Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition. Structure, 21 (6): 986-96. [PMID:23665168]

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

Dyrk2 subfamily: dual specificity tyrosine phosphorylation regulated kinase 2. Last modified on 30/03/2016. Accessed on 11/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2011.