Target General Infomation
Target ID
T10822
Former ID
TTDR00298
Target Name
Cell division protein kinase 8
Gene Name
CDK8
Synonyms
Cyclin-dependent kinase 8; Protein kinase K35; CDK8
Target Type
Research
Function
Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation.
BioChemical Class
Kinase
UniProt ID
EC Number
EC 2.7.11.23
Sequence
MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGIS
MSACREIALLRELKHPNVISLQKVFLSHADRKVWLLFDYAEHDLWHIIKFHRASKANKKP
VQLPRGMVKSLLYQILDGIHYLHANWVLHRDLKPANILVMGEGPERGRVKIADMGFARLF
NSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQED
IKTSNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKH
KVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDPLPTSDVFAGCQIPYPKREFLT
EEEPDDKGDKKNQQQQQGNNHTNGTGHPGNQDSSHTQGPPLKKVRVVPPTTTSGGLIMTS
DYQRSNPHAAYPNPGPSTSQPQSSMGYSATSQQPPQYSHQTHRY
Inhibitor compound 1 Drug Info [532762]
Oxindole 16 (compound 3) Drug Info [535564]
Oxindole 94 Drug Info [535564]
Pathways
Reactome PPARA activates gene expression
NOTCH1 Intracellular Domain Regulates Transcription
SMAD4 heterotrimer regulates transcription
Constitutive Signaling by NOTCH1 PEST Domain Mutants
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
Transcriptional regulation of white adipocyte differentiation
WikiPathways Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
SMAD4 heterotrimer
Transcriptional Regulation of White Adipocyte Differentiation
Signaling by NOTCH1
SREBP signalling
Generic Transcription Pathway
References
Ref 532762Synthesis and structure-activity relationship of trisubstituted thiazoles as Cdc7 kinase inhibitors. Eur J Med Chem. 2014 Jun 10;80:364-82.
Ref 535564Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25.

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