Names & Taxonomy
- Uniprot ID:
- Q15418
- Entry Name:
- KS6A1_HUMAN
- Status:
- reviewed
- Protein Names:
- Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1)
- Gene Names:
- RPS6KA1 MAPKAPK1A RSK1
- Gene Names Primary:
- RPS6KA1
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 735
- Sequence:
- MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPSKDEGVLKEISITHHVKAGSEKADPSHFELLKVLGQGSFGKVFLVRKVTRPDSGHLYAMKVLKKATLKVRDRVRTKMERDILADVNHPFVVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALGLDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKEAIDHEKKAYSFCGTVEYMAPEVVNRQGHSHSADWWSYGVLMFEMLTGSLPFQGKDRKETMTLILKAKLGMPQFLSTEAQSLLRALFKRNPANRLGSGPDGAEEIKRHVFYSTIDWNKLYRREIKPPFKPAVAQPDDTFYFDTEFTSRTPKDSPGIPPSAGAHQLFRGFSFVATGLMEDDGKPRAPQAPLHSVVQQLHGKNLVFSDGYVVKETIGVGSYSECKRCVHKATNMEYAVKVIDKSKRDPSEEIEILLRYGQHPNIITLKDVYDDGKHVYLVTELMRGGELLDKILRQKFFSEREASFVLHTIGKTVEYLHSQGVVHRDLKPSNILYVDESGNPECLRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFANGPSDTPEEILTRIGSGKFTLSGGNWNTVSETAKDLVSKMLHVDPHQRLTAKQVLQHPWVTQKDKLPQSQLSHQDLQLVKGAMAATYSALNSSKPTPQLKPIESSILAQRRVRKLPSTTL
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Nucleus. Cytoplasm.
Function
- Function:
- 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 pre-initiation 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). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (By similarity). 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.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Cofactor:
- COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- Enzyme Regulation:
- ENZYME REGULATION: Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-573 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-380, allowing binding of PDPK1, which in turn phosphorylates Ser-221 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD.
- Active Site:
- ACT_SITE 187 187 Proton acceptor.
- Gene Ontology Go:
- cytoplasm
cytosol
nucleoplasm
nucleus
ATP binding
cysteine-type endopeptidase inhibitor activity involved in apoptotic process
magnesium ion binding
protein serine/threonine kinase activity
protein serine/threonine/tyrosine kinase activity
axon guidance
cell cycle
hepatocyte proliferation
innate immune response
intracellular signal transduction
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of apoptotic process
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
neurotrophin TRK receptor signaling pathway
positive regulation of cell differentiation
positive regulation of cell growth
positive regulation of hepatic stellate cell activation
positive regulation of transcription from RNA polymerase II promoter
regulation of DNA-templated transcription in response to stress
regulation of translation in response to stress
signal transduction
stress-activated MAPK cascade
synaptic transmission
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway - Gene Ontology Biological Process:
- axon guidance
cell cycle
hepatocyte proliferation
innate immune response
intracellular signal transduction
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of apoptotic process
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
neurotrophin TRK receptor signaling pathway
positive regulation of cell differentiation
positive regulation of cell growth
positive regulation of hepatic stellate cell activation
positive regulation of transcription from RNA polymerase II promoter
regulation of DNA-templated transcription in response to stress
regulation of translation in response to stress
signal transduction
stress-activated MAPK cascade
synaptic transmission
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway - Gene Ontology Molecular Function:
- ATP binding
cysteine-type endopeptidase inhibitor activity involved in apoptotic process
magnesium ion binding
protein serine/threonine/tyrosine kinase activity
protein serine/threonine kinase activity - Gene Ontology Cellular Component:
- cytoplasm
cytosol
nucleoplasm
nucleus - Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Cell cycle
Complete proteome
Cytoplasm
Kinase
Magnesium
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Stress response
Transferase - Interacts With:
- P08238; P50552