TARGETID

T10822

FORMERID

TTDR00298

UNIPROID

CDK8_HUMAN

TARGNAME

Cyclin-dependent kinase 8 (CDK8)

GENENAME

CDK8

TARGTYPE

Clinical trial target

SYNONYMS

Protein kinase K35; Mediator of RNA polymerase II transcription subunit CDK8; Mediator complex subunit CDK8; Cell division protein kinase 8

FUNCTION

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. Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes.

PDBSTRUC

5XS2; 5XQX; 5IDP; 5IDN; 5ICP

BIOCLASS

Kinase

ECNUMBER

EC 2.7.11.22

SEQUENCE

MDYDFKVKLSSERERVEDLFEYEGCKVGRGTYGHVYKAKRKDGKDDKDYALKQIEGTGISMSACREIALLRELKHPNVISLQKVFLSHADRKVWLLFDYAEHDLWHIIKFHRASKANKKPVQLPRGMVKSLLYQILDGIHYLHANWVLHRDLKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDPLPTSDVFAGCQIPYPKREFLTEEEPDDKGDKKNQQQQQGNNHTNGTGHPGNQDSSHTQGPPLKKVRVVPPTTTSGGLIMTSDYQRSNPHAAYPNPGPSTSQPQSSMGYSATSQQPPQYSHQTHRY

DRUGINFO

SEL120

DRUGINFO

Macrocycle derivative 14

DRUGINFO

Tricyclic benzimidazole derivative 1

DRUGINFO

CCT251545

DRUGINFO

Oxindole 16 (compound 3)

DRUGINFO

Oxindole 94

WIKIPATH

WP1822:Generic Transcription Pathway

WIKIPATH

WP1982:SREBP signalling