CDK8

Entrez Summary: N/A
UniProt Summary: 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. {ECO:0000269|PubMed:10993082, ECO:0000269|PubMed:15546612}.

Pfam Domains GO Terms

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
Atovaquone 15μM R08 exp451	-2.29
Mitomycin-C 0.06μM R08 exp503	-2.29
SNS-032 15μM R08 exp443	-1.93
Nocodazole 0.1μM R03 exp94	-1.91
CFI-400945 25μM R08 exp469	-1.77
Genistein 15μM R07 exp360	-1.7
LB-100 4.1μM R02 exp72	1.72
THZ531 0.11 to 0.175μM on day4 R07 exp413	1.72
Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307	1.75
All-trans-Retinoic-Acid 40μM R07 exp334	1.76
INK128 0.2μM R02 exp70	1.76
Tubastatin-A 2.5μM R07 exp417	1.78
Thapsigargin 0.005μM R07 exp407	1.84
Dynasore 10μM R04 exp180	1.85
MLN-4924 0.2μM R00 exp21	1.85
UM0129480 7μM R02 exp85	1.87
Rapamycin 0.001μM R08 exp429	1.88
Bortezomib 0.005μM R00 exp6	1.92
All-trans-Retinoic-Acid 8μM R07 exp333	1.95
Nicotinamide 2000μM R01 exp50	1.97
Vemurafenib 6.6μM R08 exp434	2.01
Losmapimod 1μM R07 exp376	2.05
Oligomycin-A 2μM R00 exp25	2.06
Salubrinal 20μM R07 exp399	2.06
Tunicamycin 0.04μM R07 exp418	2.09
GSK-J4 1μM R07 exp362	2.28
BI-D1870 2μM R04 exp162	2.32
Tunicamycin 0.04 to 0.125μM on day4 R07 exp420	2.38
Rapamycin 2μM plus FK-506 5μM R07 exp308	2.42
Trametinib 10μM R02 exp83	2.43
Tunicamycin 0.04 to 0.075μM on day4 R07 exp419	2.6
MK2206 4μM R08 exp504	2.81
I-BRD9 4μM R07 exp365	3.01
Rapamycin 2μM R07 exp306	3.54
Rapamycin 10μM R00 exp30	3.81
Rapamycin 1μM R00 exp29	4

Global Fraction of Cell Lines Where Essential: 7/726

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/25
breast	0/33
central nervous system	2/56
cervix	0/4
colorectal	1/17
esophagus	0/13
fibroblast	0/1
gastric	0/15
kidney	0/21
liver	0/20
lung	2/75
lymphocyte	0/14
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	1/15
prostate	0/1
skin	0/24
soft tissue	0/7
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Expression Distribution

Pkinase Tyr
Pkinase

RNA polymerase II CTD heptapeptide repeat kinase activity
cyclin-dependent protein serine/threonine kinase activity
mediator complex
transcription initiation from RNA polymerase II promoter
DNA-templated transcription, initiation
protein kinase activity
transcription by RNA polymerase II
protein-containing complex
transcription, DNA-templated
nucleic acid-templated transcription
RNA biosynthetic process
nucleolus
protein phosphorylation
nucleobase-containing compound biosynthetic process
heterocycle biosynthetic process
aromatic compound biosynthetic process
regulation of cell cycle
positive regulation of transcription by RNA polymerase II
phosphorylation
organic cyclic compound biosynthetic process
ATP binding
positive regulation of transcription, DNA-templated
cellular nitrogen compound biosynthetic process
positive regulation of nucleic acid-templated transcription
positive regulation of RNA biosynthetic process
RNA metabolic process
cellular macromolecule biosynthetic process
positive regulation of RNA metabolic process
macromolecule biosynthetic process
positive regulation of nucleobase-containing compound metabolic process
positive regulation of macromolecule biosynthetic process
positive regulation of cellular biosynthetic process
positive regulation of gene expression
gene expression
positive regulation of biosynthetic process