Tchem CDK8 Cyclin-dependent kinase 8

Protein Summary

Description

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. This gene encodes a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are known to be important regulators of cell cycle progression. This kinase and its regulatory subunit, cyclin C, are components of the Mediator transcriptional regulatory complex, involved in both transcriptional activation and repression by phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II. This kinase regulates transcription by targeting the cyclin-dependent kinase 7 subunits of the general transcription initiation factor IIH, thus providing a link between the Mediator complex and the basal transcription machinery. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

Uniprot Accession IDs

• P49336
• Q5VUF3
• Q6ISB5

Gene Name

• CDK8

Ensembl ID

• ENST00000381527
• ENSP00000370938
• ENSG00000132964

Symbol

• K35

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.95
disease perturbation	0.93
transcription factor binding site profile	0.88
histone modification site profile	0.84
trait	0.75

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Tyrosine Protein Kinase / Cyclin-dependent Kinase 8

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Cyclin-dependent Kinase 8

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Cdk Family / Cdk8 Subfamily / Cyclin-dependent Kinase 8

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 282.33   (req: < 5)

Gene RIFs: 84   (req: <= 3)

Antibodies: 408   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 282.33   (req: >= 5)

Gene RIFs: 84   (req: > 3)

Antibodies: 408   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 8

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 196

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2