Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTR93NU)

• DTT Name: Casein kinase II alpha prime (CSNK2A2)
• Synonyms: Casein kinase II subunit alpha'; CK2A2; CK II alpha'
• Gene Name: CSNK2A2
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Kinase
• UniProt ID: CSK22_HUMAN
• TTD ID: T80526
• EC Number: EC 2.7.11.1
• Sequence:
  MPGPAAGSRARVYAEVNSLRSREYWDYEAHVPSWGNQDDYQLVRKLGRGKYSEVFEAINI
  TNNERVVVKILKPVKKKKIKREVKILENLRGGTNIIKLIDTVKDPVSKTPALVFEYINNT
  DFKQLYQILTDFDIRFYMYELLKALDYCHSKGIMHRDVKPHNVMIDHQQKKLRLIDWGLA
  EFYHPAQEYNVRVASRYFKGPELLVDYQMYDYSLDMWSLGCMLASMIFRREPFFHGQDNY
  DQLVRIAKVLGTEELYGYLKKYHIDLDPHFNDILGQHSRKRWENFIHSENRHLVSPEALD
  LLDKLLRYDHQQRLTAKEAMEHPYFYPVVKEQSQPCADNAVLSSGLTAAR
• 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. 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.
• KEGG Pathway:
  Ribosome biogenesis in eukaryotes (hsa03008)
  NF-kappa B signaling pathway (hsa04064)
  Mitophagy - animal (hsa04137)
  Wnt signaling 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)
  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 DTT

6 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US8791257, 17	DMUPRX2	N. A.	N. A.	Patented	[2]
US8791257, 38	DMAEHCP	N. A.	N. A.	Patented	[2]
US8791257, 4	DMIQO8N	N. A.	N. A.	Patented	[2]
US8940736, 23	DM3PU57	N. A.	N. A.	Patented	[3]
US8940736, 6	DMXY4SP	N. A.	N. A.	Patented	[3]
US8940736, 7	DM9KSVI	N. A.	N. A.	Patented	[3]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID22115617C2c	DMX5UKA	Discovery agent	N.A.	Investigative	[1]

References

• [1] 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.
• [2] Substituted pyrrolotriazines as protein kinase inhibitors. US8791257.
• [3] Imidazotriazinecarbonitriles useful as kinase inhibitors. US8940736.