Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

RPS6KA4 (O75676) - Overview - Molecular Target Synopsis

Protein


RPS6KA4, Ribosomal protein S6 kinase alpha-4
Enzyme Classification 2.7.11.1
UniProt O75676

Also Known as KS6A4_HUMAN, RPS6KA4, MSK2

Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA4 associates with and phosphorylates the NF-kappa-B p65 subunit RELA.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: RPS6KA4 is active in the following subcellular-locations: nucleus.
GO terms: RPS6KA4 is active in the following subcellular-locations: cytoplasm, cytosol, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project RPS6KA4 has gain in 3 cell-lines, loss in 0 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MDA_MB_231, TK_10, DU_145

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Ca Ski, CAL-12T, BHY

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, HMEC, A549

(see details)

RNA Interference


RPS6KA4 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SKGT4, KPD. (see details)

3D Structures


At greater than 50% identity similarity to RPS6KA4 there are:
29 structures (37 chains) solved
27 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RPS6KA4 has been screened with 756 compounds (1552 bioactivities), 15 compounds have bioactivities that show binding affinity of <= 500nM (21 bioactivities). (see details)