Cancer Protein Description
This report provides a detailed description of a selected cancer protein with information collected from various sources, including UniProt, the Wellcome Trust Sanger Institute’s Catalogue of Somatic Mutations in Cancer (COSMIC), and the Atlas of Genetics and Cytogenetics in Oncology and Haematology.
| Protein Name: | RPS6KA1 |
| Gene Name: | RPS6KA1 |
| Protein Full Name: | Ribosomal protein S6 kinase alpha-1 |
| Alias: | 90 kDa ribosomal protein S6 kinase 1; EC 2.7.11.1; HU-1; Kinase p90RSK1; KS6A1; KS6AA; MAPKAP-K1a; P90-RSK 1; P90RSK1; Pp90RSK1; Ribosomal protein S6 kinase alpha 1; Ribosomal protein S6 kinase, 90kDa, polypeptide 1; Ribosomal S6 kinase 1; RSK; RSK1; RSK-1; S6K-alpha 1 |
| Mass (Da): | 82723 |
| Number AA: | 735 |
| UniProt ID: | Q15418 |
| Locus ID: | 6195 |
| COSMIC ID: | RPS6KA1 |
| Gene location on chromosome: | 1p36.11 |
| Cancer protein type: | OP |
| Effect of cancer mutation on protein: | GAIN |
| Effect of active protein on cancer: | PROMOTES |
| Number of cancer specimens: | 20005 |
| Percent of cancer specimens with mutations: | 0.43 |
| Normal role description: | RSK1 is a RSK (ribosomal S6 kinase) family of serine/threonine kinases. RSK1 contains 2 nonidentical kinase catalytic domains. RSK1 is known phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway -- a pro-growth/anti-apoptotic pathway, as it will activate CREB, which in turn will upregulate expression of cylin-D and c-Myc. Activation of this pathway is common in various types of tumors. In some cases, such breast and prostate cancer, upreguation of RSK has been shown in some patients. |
| Commentary on involvement of protein in cancer: | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling 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 signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, 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. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. |