Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2WW7R1)

• DOT Name: Casein kinase II subunit beta (CSNK2B)
• Synonyms: CK II beta; Phosvitin; Protein G5a
• Gene Name: CSNK2B
• Related Disease:
  Poirier-Bienvenu neurodevelopmental syndrome
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Cholangiocarcinoma
  Congenital contractural arachnodactyly
  Epilepsy
  Epstein barr virus infection
  Familial adenomatous polyposis
  Intellectual disability
  Lung cancer
  Lung carcinoma
  Neurodevelopmental disorder
  Rheumatoid arthritis
  Schizophrenia
  Type-1 diabetes
  Adult T-cell leukemia/lymphoma
  Cutaneous lupus erythematosus
  Skin cancer
  Skin neoplasm
  Squamous cell carcinoma
  Autosomal dominant non-syndromic intellectual disability
  Endometrium neoplasm
  Advanced cancer
  Myocardial infarction
  Systemic lupus erythematosus
• UniProt ID: CSK2B_HUMAN
• PDB ID: 1DS5; 1JWH; 1QF8; 3EED; 4DGL; 4MD7; 4MD8; 4MD9; 4NH1; 6Q38
• Pfam ID: PF01214
• Sequence:
  MSSSEEVSWISWFCGLRGNEFFCEVDEDYIQDKFNLTGLNEQVPHYRQALDMILDLEPDE
  ELEDNPNQSDLIEQAAEMLYGLIHARYILTNRGIAQMLEKYQQGDFGYCPRVYCENQPML
  PIGLSDIPGEAMVKLYCPKCMDVYTPKSSRHHHTDGAYFGTGFPHMLFMVHPEYRPKRPA
  NQFVPRLYGFKIHPMAYQLQLQAASNFKSPVKTIR
• Function: Regulatory subunit of casein kinase II/CK2. As part of the kinase complex regulates the basal catalytic activity of the alpha subunit a constitutively active serine/threonine-protein kinase that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Participates in Wnt signaling; (Microbial infection) Upon infection with Epstein-Barr virus (EBV), the interaction with viral EBNA1 increases the association of CK2 with PML proteins, which increases PML phosphorylation by CK2, triggering the polyubiquitylation and degradation of PML. Seems to also suppress EBV reactivation by mediating ARK2N and JUN at the Z promoter which inhibits BZLF1 transcrition.
• KEGG Pathway:
  Ribosome biogenesis in eukaryotes (hsa03008)
  Polycomb repressive complex (hsa03083)
  NF-kappa B sig.ling pathway (hsa04064)
  Mitophagy - animal (hsa04137)
  Wnt sig.ling pathway (hsa04310)
  Adherens junction (hsa04520)
  Alzheimer disease (hsa05010)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Measles (hsa05162)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
• Reactome Pathway:
  WNT mediated activation of DVL (R-HSA-201688)
  Condensation of Prometaphase Chromosomes (R-HSA-2514853)
  Signal transduction by L1 (R-HSA-445144)
  Neutrophil degranulation (R-HSA-6798695)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding (R-HSA-6814122)
  Receptor Mediated Mitophagy (R-HSA-8934903)
  RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243)
  Regulation of PTEN stability and activity (R-HSA-8948751)
  KEAP1-NFE2L2 pathway (R-HSA-9755511)
  Synthesis of PC (R-HSA-1483191)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Poirier-Bienvenu neurodevelopmental syndrome	DISDC63F	Definitive	Autosomal dominant	[1]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[4]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[4]
Epilepsy	DISBB28L	Strong	Genetic Variation	[5]
Epstein barr virus infection	DISOO0WT	Strong	Genetic Variation	[6]
Familial adenomatous polyposis	DISW53RE	Strong	Altered Expression	[7]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[8]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[9]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[9]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[8]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[10]
Schizophrenia	DISSRV2N	Strong	Biomarker	[11]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[12]
Adult T-cell leukemia/lymphoma	DIS882XU	moderate	Biomarker	[13]
Cutaneous lupus erythematosus	DISOIX6L	moderate	Genetic Variation	[14]
Skin cancer	DISTM18U	moderate	Biomarker	[15]
Skin neoplasm	DIS16DDV	moderate	Biomarker	[15]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[15]
Autosomal dominant non-syndromic intellectual disability	DISD6L06	Supportive	Autosomal dominant	[16]
Endometrium neoplasm	DIS6OS2L	Disputed	Altered Expression	[17]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[18]
Myocardial infarction	DIS655KI	Limited	Biomarker	[19]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[20]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Casein kinase II subunit beta (CSNK2B).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Casein kinase II subunit beta (CSNK2B).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Casein kinase II subunit beta (CSNK2B).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Casein kinase II subunit beta (CSNK2B).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Casein kinase II subunit beta (CSNK2B).	[25]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Casein kinase II subunit beta (CSNK2B).	[27]
Selenium	DM25CGV	Approved	Selenium increases the expression of Casein kinase II subunit beta (CSNK2B).	[28]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Casein kinase II subunit beta (CSNK2B).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Casein kinase II subunit beta (CSNK2B).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Casein kinase II subunit beta (CSNK2B).	[32]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin affects the binding of Casein kinase II subunit beta (CSNK2B).	[26]
Adenosine triphosphate	DM79F6G	Approved	Adenosine triphosphate affects the binding of Casein kinase II subunit beta (CSNK2B).	[30]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Capsaicin	DMGMF6V	Approved	Capsaicin increases the phosphorylation of Casein kinase II subunit beta (CSNK2B).	[29]

References

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• [2] Relapsed diffuse large B-cell lymphoma present different genomic profiles between early and late relapses.Oncotarget. 2016 Dec 20;7(51):83987-84002. doi: 10.18632/oncotarget.9793.
• [3] Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets for triple negative breast cancer therapy.Breast Cancer Res. 2015;17:19. doi: 10.1186/s13058-015-0524-0. Epub 2015 Feb 11.
• [4] Overexpressions of CK2 and XIAP are associated with poor prognosis of patients with cholangiocarcinoma.Pathol Oncol Res. 2014 Jan;20(1):73-9. doi: 10.1007/s12253-013-9660-y. Epub 2013 Jul 5.
• [5] Germline de novo variants in CSNK2B in Chinese patients with epilepsy.Sci Rep. 2019 Nov 29;9(1):17909. doi: 10.1038/s41598-019-53484-9.
• [6] A genome-wide integrative genomic study localizes genetic factors influencing antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA-1).PLoS Genet. 2013;9(1):e1003147. doi: 10.1371/journal.pgen.1003147. Epub 2013 Jan 10.
• [7] Association and regulation of casein kinase 2 activity by adenomatous polyposis coli protein.Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5959-64. doi: 10.1073/pnas.092143199. Epub 2002 Apr 23.
• [8] Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures.J Hum Genet. 2019 Apr;64(4):313-322. doi: 10.1038/s10038-018-0559-z. Epub 2019 Jan 17.
• [9] Novel genetic variants in the P38MAPK pathway gene ZAK and susceptibility to lung cancer.Mol Carcinog. 2018 Feb;57(2):216-224. doi: 10.1002/mc.22748. Epub 2017 Oct 31.
• [10] A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.Ann Rheum Dis. 2011 Feb;70(2):259-65. doi: 10.1136/ard.2009.126821. Epub 2010 Dec 14.
• [11] Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes.Nat Commun. 2018 Feb 26;9(1):838. doi: 10.1038/s41467-018-03247-3.
• [12] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [13] Integrated molecular analysis of adult T cell leukemia/lymphoma.Nat Genet. 2015 Nov;47(11):1304-15. doi: 10.1038/ng.3415. Epub 2015 Oct 5.
• [14] Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus.Exp Dermatol. 2015 Jul;24(7):510-5. doi: 10.1111/exd.12708. Epub 2015 May 4.
• [15] Arsenic-induced malignant transformation of human keratinocytes: involvement of Nrf2.Free Radic Biol Med. 2008 Sep 1;45(5):651-8. doi: 10.1016/j.freeradbiomed.2008.05.020. Epub 2008 Jun 3.
• [16] CSNK2B splice site mutations in patients cause intellectual disability with or without myoclonic epilepsy. Hum Mutat. 2017 Aug;38(8):932-941. doi: 10.1002/humu.23270. Epub 2017 Jun 19.
• [17] CK2beta is expressed in endometrial carcinoma and has a role in apoptosis resistance and cell proliferation.Am J Pathol. 2009 Jan;174(1):287-96. doi: 10.2353/ajpath.2009.080552. Epub 2008 Dec 4.
• [18] In vivo siRNA distribution and pharmacokinetics assessed by nuclear imaging are modulated according to radiolabelling site.Nucl Med Biol. 2015 Dec;42(12):958-66. doi: 10.1016/j.nucmedbio.2015.04.007. Epub 2015 Apr 24.
• [19] Differential gene expression in infarct scar and viable myocardium from rat heart following coronary ligation.J Cell Mol Med. 2004 Jan-Mar;8(1):85-92. doi: 10.1111/j.1582-4934.2004.tb00262.x.
• [20] Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry.Arthritis Rheumatol. 2016 Jan;68(1):174-83. doi: 10.1002/art.39403.
• [21] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [22] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [23] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [24] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [25] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [26] Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. Bioorg Med Chem. 2011 Aug 15;19(16):4710-20. doi: 10.1016/j.bmc.2011.07.005. Epub 2011 Jul 13.
• [27] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [28] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [29] Capsaicin, a component of red peppers, stimulates protein kinase CKII activity. BMB Rep. 2010 May;43(5):325-9. doi: 10.5483/bmbrep.2010.43.5.325.
• [30] 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. 2011 Jan 27;54(2):635-54.
• [31] Comparison of quantitation methods in proteomics to define relevant toxicological information on AhR activation of HepG2 cells by BaP. Toxicology. 2021 Jan 30;448:152652. doi: 10.1016/j.tox.2020.152652. Epub 2020 Dec 2.
• [32] Modelling cardiac fibrosis using three-dimensional cardiac microtissues derived from human embryonic stem cells. J Biol Eng. 2019 Feb 13;13:15. doi: 10.1186/s13036-019-0139-6. eCollection 2019.