Target Information
Target General Information | Top | |||||
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Target ID |
T51565
(Former ID: TTDR00257)
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Target Name |
Casein kinase II alpha (CSNK2A1)
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Synonyms |
Protein kinase CK2; Casein kinase II subunit alpha; CK2A1; CK II alpha; CK II
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Gene Name |
CSNK2A1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 3 Target-related Diseases | + | ||||
1 | Coronavirus infection [ICD-11: 1D92] | |||||
2 | Liver cancer [ICD-11: 2C12] | |||||
3 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation. Plays an important role in the circadian clock function by phosphorylating ARNTL/BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry. Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue. Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine.
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BioChemical Class |
Kinase
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UniProt ID | ||||||
EC Number |
EC 2.7.11.1
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Sequence |
MSGPVPSRARVYTDVNTHRPREYWDYESHVVEWGNQDDYQLVRKLGRGKYSEVFEAINIT
NNEKVVVKILKPVKKKKIKREIKILENLRGGPNIITLADIVKDPVSRTPALVFEHVNNTD FKQLYQTLTDYDIRFYMYEILKALDYCHSMGIMHRDVKPHNVMIDHEHRKLRLIDWGLAE FYHPGQEYNVRVASRYFKGPELLVDYQMYDYSLDMWSLGCMLASMIFRKEPFFHGHDNYD QLVRIAKVLGTEDLYDYIDKYNIELDPRFNDILGRHSRKRWERFVHSENQHLVSPEALDF LDKLLRYDHQSRLTAREAMEHPYFYTVVKDQARMGSSSMPGGSTPVSSANMMSGISSVPT PSPLGPLAGSPVIAAANPLGMPVPAAAGAQQ Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T40GZM |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | CX-4945 | Drug Info | Phase 2 | Coronavirus infection | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 17 Inhibitor drugs | + | ||||
1 | CX-4945 | Drug Info | [1] | |||
2 | BALANOL | Drug Info | [3] | |||
3 | EMODIN | Drug Info | [4] | |||
4 | 4,5,6,7-tetrabromo-1H-benzimidazole | Drug Info | [5] | |||
5 | 4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole | Drug Info | [4] | |||
6 | 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol | Drug Info | [6] | |||
7 | 5,6,8-trichloroquinoline-4-one-3-carboxylic acid | Drug Info | [7] | |||
8 | 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole | Drug Info | [4] | |||
9 | 7,8-dichloroquinoline-4-one-3-carboxylic acid | Drug Info | [7] | |||
10 | AdoC(Dpr)2AlaArg6 | Drug Info | [8] | |||
11 | APIGENIN | Drug Info | [4] | |||
12 | CGP-029482 | Drug Info | [4] | |||
13 | CX-5011 | Drug Info | [9] | |||
14 | CX-7000 | Drug Info | [9] | |||
15 | ELLAGIC ACID | Drug Info | [4] | |||
16 | PMID22115617C2c | Drug Info | [10] | |||
17 | PMID24900749C1a | Drug Info | [11] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-regulating Transcription Factors | ||||||
Target-interacting Proteins |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 2 | ClinicalTrials.gov (NCT04668209) Silmitasertib (CX-4945) in Patients With Severe Coronavirus Disease 2019 (COVID-19) (CX4945). U.S. National Institutes of Health. | |||||
REF 3 | Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A. J Med Chem. 1996 Dec 20;39(26):5215-27. | |||||
REF 4 | Structural insight into human CK2alpha in complex with the potent inhibitor ellagic acid. Bioorg Med Chem Lett. 2009 Jun 1;19(11):2920-3. | |||||
REF 5 | Synthesis of new analogs of benzotriazole, benzimidazole and phthalimide--potential inhibitors of human protein kinase CK2. Bioorg Med Chem. 2009 Feb 15;17(4):1573-8. | |||||
REF 6 | 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9. | |||||
REF 7 | Evaluation of 3-carboxy-4(1H)-quinolones as inhibitors of human protein kinase CK2. J Med Chem. 2006 Nov 2;49(22):6443-50. | |||||
REF 8 | Adenosine-5'-carboxylic acid peptidyl derivatives as inhibitors of protein kinases. Bioorg Med Chem Lett. 1999 May 17;9(10):1447-52. | |||||
REF 9 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1549). | |||||
REF 10 | CK2alpha and CK2alpha' subunits differ in their sensitivity to 4,5,6,7-tetrabromo- and 4,5,6,7-tetraiodo-1H-benzimidazole derivatives. Eur J Med Chem. 2012 Jan;47(1):345-50. | |||||
REF 11 | Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo. ACS Med Chem Lett. 2013 Jul 3;4(8):800-5. |
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