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casein kinase 2, alpha 1 polypeptide subunit

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Target id: 1549

Nomenclature: casein kinase 2, alpha 1 polypeptide subunit

Abbreviated Name: CK2-A1

Family: Casein kinase 2 (CK2) family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 391 20p13 CSNK2A1 casein kinase 2 alpha 1
Mouse - 391 2 G3 Csnk2a1 casein kinase 2, alpha 1 polypeptide
Rat - 391 3q41 Csnk2a1 casein kinase 2 alpha 1
Previous and Unofficial Names Click here for help
casein kinase 2 | casein kinase II subunit alpha | CK II alpha
Database Links Click here for help
Alphafold P68400 (Hs), Q60737 (Mm), P19139 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL3629 (Hs), CHEMBL3537 (Mm), CHEMBL3988629 (Rn)
Ensembl Gene ENSG00000101266 (Hs), ENSMUSG00000074698 (Mm), ENSRNOG00000005276 (Rn)
Entrez Gene 1457 (Hs), 12995 (Mm), 116549 (Rn)
Human Protein Atlas ENSG00000101266 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:1457 (Hs), mmu:12995 (Mm), rno:116549 (Rn)
OMIM 115440 (Hs)
Pharos P68400 (Hs)
RefSeq Nucleotide NM_001895 (Hs), NM_007788 (Mm), NM_053824 (Rn)
RefSeq Protein NP_001886 (Hs), NP_031814 (Mm), NP_446276 (Rn)
SynPHARM 81435 (in complex with compound 1a [PMID: 24900749])
81423 (in complex with CX-4945)
UniProtKB P68400 (Hs), Q60737 (Mm), P19139 (Rn)
Wikipedia CSNK2A1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of CK2alpha.
PDB Id:  3AT2
Resolution:  1.6Å
Species:  Human
References:  9
Image of receptor 3D structure from RCSB PDB
Description:  Human CK2 catalytic domain in complex with AMPPN.
PDB Id:  3NSZ
Resolution:  1.3Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  Structural basis of CX-4945 binding to human protein kinase CK2.
PDB Id:  3NGA
Ligand:  silmitasertib
Resolution:  2.71Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human protein kinase CK2 in complex with the inhibitor CX-5011.
PDB Id:  3PE2
Ligand:  CX-5011
Resolution:  1.9Å
Species:  Human
References:  2
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
compound 2c [PMID: 22115617] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pKi 8
⤷ pKi 7.1 (Ki 8.3x10-8 M) [8]
silmitasertib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 10
⤷ pIC50 9.0 (IC50 1x10-9 M) [10]
compound 1a [PMID: 24900749] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pIC50 5
⤷ pIC50 8.0 (IC50 1x10-8 M) [5]
Inhibitor Comments
The CK2 inhibitor TBB (PubChem CID 1694) has an IC50 of 500nM vs. the human CK2α catalytic subunit CSNK2A1 [3].
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: 4,11
Key to terms and symbols Click column headers to sort
Target used in screen: CSNK2A1
Ligand Sp. Type Action Value Parameter
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 5.7 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 5.6 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.6 pKd
TG-100-115 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.6 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: 1,7
Key to terms and symbols Click column headers to sort
Target used in screen: CK2/CK2a
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
PI 3-Kg inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.1 -13.0 -12.0
casein kinase II inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 13.1 12.0 -8.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 16.7 74.0 101.0
JNK inhibitor V Small molecule or natural product Hs Inhibitor Inhibition 22.1 58.0 15.0
PI 3-Kg inhibitor II Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 22.6 32.0 2.0
PKR inhibitor, negative control Small molecule or natural product Hs Inhibitor Inhibition 26.5 41.0 4.0
GSK-3 inhibitor XIII Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 27.0 43.0 -2.0
STO609 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 28.3 22.0 -4.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 48.2 30.0 1.0
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 52.6 60.0 21.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
CSNK2A1 is included in Guide to IMMUNOPHARMACOLOGY as it is a subunit of the casein kinase 2 complex.

References

Show »

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. Battistutta R, Cozza G, Pierre F, Papinutto E, Lolli G, Sarno S, O'Brien SE, Siddiqui-Jain A, Haddach M, Anderes K et al.. (2011) Unprecedented selectivity and structural determinants of a new class of protein kinase CK2 inhibitors in clinical trials for the treatment of cancer. Biochemistry, 50 (39): 8478-88. [PMID:21870818]

3. Battistutta R, Mazzorana M, Sarno S, Kazimierczuk Z, Zanotti G, Pinna LA. (2005) Inspecting the structure-activity relationship of protein kinase CK2 inhibitors derived from tetrabromo-benzimidazole. Chem Biol, 12 (11): 1211-9. [PMID:16298300]

4. 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]

5. Dowling JE, Alimzhanov M, Bao L, Block MH, Chuaqui C, Cooke EL, Denz CR, Hird A, Huang S, Larsen NA et al.. (2013) Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo. ACS Med Chem Lett, 4 (8): 800-5. [PMID:24900749]

6. Ferguson AD, Sheth PR, Basso AD, Paliwal S, Gray K, Fischmann TO, Le HV. (2011) Structural basis of CX-4945 binding to human protein kinase CK2. FEBS Lett, 585 (1): 104-10. [PMID:21093442]

7. 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]

8. Janeczko M, Orzeszko A, Kazimierczuk Z, Szyszka R, Baier A. (2012) CK2α and CK2α' subunits differ in their sensitivity to 4,5,6,7-tetrabromo- and 4,5,6,7-tetraiodo-1H-benzimidazole derivatives. Eur J Med Chem, 47 (1): 345-50. [PMID:22115617]

9. Kinoshita T, Sekiguchi Y, Fukada H, Nakaniwa T, Tada T, Nakamura S, Kitaura K, Ohno H, Suzuki Y, Hirasawa A et al.. (2011) A detailed thermodynamic profile of cyclopentyl and isopropyl derivatives binding to CK2 kinase. Mol Cell Biochem, 356 (1-2): 97-105. [PMID:21735094]

10. Pierre F, Chua PC, O'Brien SE, Siddiqui-Jain A, Bourbon P, Haddach M, Michaux J, Nagasawa J, Schwaebe MK, Stefan E et al.. (2011) Discovery and SAR of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer. J Med Chem, 54 (2): 635-54. [PMID:21174434]

11. 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

Casein kinase 2 (CK2) family: casein kinase 2, alpha 1 polypeptide subunit. Last modified on 23/08/2017. Accessed on 04/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1549.