RPS6KA3
RPS6KA3 (Ribosomal protein S6 kinase alpha-3) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Hepatocellular carcinoma.
Overview
Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signalling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signalling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP.
Open Targets scores its association with cancer at 0.54 (direct and indirect evidence; datatypes literature 0.96, genetic association 0.00, somatic mutation 0.84). IntOGen calls it a driver in 4 cohorts (0 activating, 4 loss-of-function), covering Hepatocellular Carcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · RPS6KA3 (Ribosomal protein S6 kinase alpha-3) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Hepatocellular carcinoma.
- 1 · What it is
RPS6KA3 (Ribosomal protein S6 kinase alpha-3) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Hepatocellular carcinoma.
- 2 · What goes wrong in cancer
Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signalling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signalling and repressing pro-apoptotic function of BAD and DAPK1.
- 3 · How drugs use it
No product in this corpus aims at RPS6KA3 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:10432 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P51812 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000177189 (association with cancer (MONDO_0004992) 0.54; per-cancer scores at or above 0.5: hepatocellular carcinoma 0.54 (GraphQL API, CC0)); IntOGen RPS6KA3 (driver in 4 cohorts (Act 0, LoF 4); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signalling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signalling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Location: Nucleus; Cytoplasm (UniProt). Locus Xp22.12 (HGNC).
- Hepatocellular carcinoma: Open Targets association 0.54 with hepatocellular carcinoma (MONDO_0007256); IntOGen driver in 4 cohorts (HCC)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it a loss-of-function (LoF) driver in 4 cohorts. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"RPS6KA3" OR ABSTRACT:"RPS6KA3" OR TITLE:"ribosomal protein S6 kinase A3" OR ABSTRACT:"ribosomal protein S6 kinase A3" OR TITLE:"Ribosomal protein S6 kinase alpha-3" OR ABSTRACT:"Ribosomal protein S6 kinase alpha-3" OR TITLE:"RSK2" OR ABSTRACT:"RSK2" OR TITLE:"HU-3" OR ABSTRACT:"HU-3" OR TITLE:"MRX19" OR ABSTRACT:"MRX19") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about RPS6KA3, not a curated reading list.