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

RPS6KA5 (O75582) - Overview - Molecular Target Synopsis

Protein


RPS6KA5, Ribosomal protein S6 kinase alpha-5
Enzyme Classification 2.7.11.1
UniProt O75582

Also Known as KS6A5_HUMAN, RPS6KA5, MSK1

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 factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (PubMed:11909979, PubMed:12569367, PubMed:12763138, PubMed:9687510, PubMed:18511904, PubMed:9873047). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin (PubMed:11909979, PubMed:9873047). Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression (PubMed:12628924, PubMed:18511904). In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress (PubMed:12628924). In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential (PubMed:12763138). Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation (PubMed:12569367). Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A (PubMed:15010469). 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 (PubMed:12773393). May also phosphorylate 'Ser-28' of histone H3 (PubMed:12773393). Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (PubMed:12773393). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines (By similarity). 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 (By similarity). Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury (By similarity). Phosphorylates TRIM7 at 'Ser-107' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity (PubMed:25851810). 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 RPS6KA5 associates with and phosphorylates the NF-kappa-B p65 subunit RELA. Interacts with CREBBP and EP300.

3KN5
CRYSTAL STRUCTURE OF THE C-TERMINAL KINASE DOMAIN OF MSK1 IN COMPLEX WITH AMP-PNP
RCSB/PDB
Inspect Structure
See all 3D Structures for RPS6KA5

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: RPS6KA5 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: RPS6KA5 is active in the following subcellular-locations: cytoplasm, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project RPS6KA5 has gain in 8 cell-lines, loss in 3 cell-lines and no signal in 994 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_MEL_28, OVCAR_5, MALME_3M

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SK-N-FI, NCI-H1581, LN-18

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, NHLF, HSMM

(see details)

RNA Interference


RPS6KA5 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CAL120, BT549. (see details)

3D Structures


For RPS6KA5 there are:
3 structures (5 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RPS6KA5 has been screened with 1238 compounds (2163 bioactivities), 58 compounds have bioactivities that show binding affinity of <= 500nM (85 bioactivities). (see details)