Cyclin-dependent kinase 19

UniProt Q9BWU1 Organism Homo sapiens Gene CDC2L6, CDK11, CDK19, KIAA1028 EC 2.7.11.22

Also known as: CDC2L6, CDK11, CDK19, KIAA1028

Function

Component of the Mediator complex, a transcriptional coactivator required for regulated expression of nearly all RNA polymerase II-dependent genes. Acts as a molecular bridge between gene-specific regulatory proteins and the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters through direct interactions with transcriptional regulators and serves as a scaffold for assembly of the pre-initiation complex with RNA polymerase II and general transcription factors. Contributes to phosphorylation of transcription factors and other substrates, including RNA polymerase II and the Notch1 intracellular domain (ICN1), thereby modulating gene expression programs. Plays a role together with CDK8 in normal macrophage differentiation (By similarity).

Classification

Family (Pfam): PF00069 Pkinase
InterPro: CDK, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
Functional cluster: RNA-Polymerase II Transcription Factors

Gene Ontology · 10

Disease associations

developmental and epileptic encephalopathy, 87 MONDO:0030059

Drugs targeting this protein · 4

PHA-793887 inhibitor
RONICICLIB inhibitor
AT-7519 inhibitor
AZD-5438 inhibitor

Related proteins · sequence + function similarity

Cyclin-dependent kinase 19 1.00
Cyclin-dependent kinase 8 0.98
Cyclin-dependent kinase 8 0.98
Cyclin-dependent kinase 8 0.98
Cyclin-dependent kinase 8 0.97
Cyclin-dependent kinase 8 0.91
Cyclin-dependent kinase 8 0.88
Cyclin-dependent kinase 8 0.87
Serine/threonine-protein kinase NLK 0.75
Serine/threonine-protein kinase NLK 0.75
Serine/threonine-protein kinase NLK 0.75
Serine/threonine-protein kinase NLK 0.75

Co-cited proteins · studied together in the literature

Cyclin-C 1 shared papers
Mediator of RNA polymerase II transcription subunit 12 1 shared papers

Literature · 13 cited papers

CDK19-related disorder results from both loss-of-function and gain-of-function de novo missense variants. Genet. Med. · 2021
Cerebrospinal fluid abnormalities in developmental and epileptic encephalopathy with a de novo CDK19 variant. Neurol. Genet. · 2020
De novo variants in CDK19 are associated with a syndrome involving intellectual disability and epileptic encephalopathy. Am. J. Hum. Genet. · 2020
Oncogenic exon 2 mutations in Mediator subunit MED12 disrupt allosteric activation of cyclin C-CDK8/19. J. Biol. Chem. · 2018
CDK8/19 Mediator kinases potentiate induction of transcription by NFkappaB. Proc. Natl. Acad. Sci. U.S.A. · 2017
Cyclin C is a haploinsufficient tumour suppressor. Nat. Cell Biol. · 2014
N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
The DNA sequence and analysis of human chromosome 6. Nature · 2003
Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. DNA Res. · 2002
… and 1 more in the literature graph

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