Drug Miner Browse

Names & Taxonomy

Uniprot ID:: P51812
Entry Name:: KS6A3_HUMAN
Status:: reviewed
Protein Names:: Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2)
Gene Names:: RPS6KA3 ISPK1 MAPKAPK1B RSK2
Gene Names Primary:: RPS6KA3
Organism:: Homo sapiens (Human)

Structure

Length:: 740
Sequence:: MPLAQLADPWQKMAVESPSDSAENGQQIMDEPMGEEEINPQTEEVSIKEIAITHHVKEGHEKADPSQFELLKVLGQGSFGKVFLVKKISGSDARQLYAMKVLKKATLKVRDRVRTKMERDILVEVNHPFIVKLHYAFQTEGKLYLILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFGLSKESIDHEKKAYSFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGTLPFQGKDRKETMTMILKAKLGMPQFLSPEAQSLLRMLFKRNPANRLGAGPDGVEEIKRHSFFSTIDWNKLYRREIHPPFKPATGRPEDTFYFDPEFTAKTPKDSPGIPPSANAHQLFRGFSFVAITSDDESQAMQTVGVHSIVQQLHRNSIQFTDGYEVKEDIGVGSYSVCKRCIHKATNMEFAVKIIDKSKRDPTEEIEILLRYGQHPNIITLKDVYDDGKYVYVVTELMKGGELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYVDESGNPESIRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDAACDIWSLGVLLYTMLTGYTPFANGPDDTPEEILARIGSGKFSLSGGYWNSVSDTAKDLVSKMLHVDPHQRLTAALVLRHPWIVHWDQLPQYQLNRQDAPHLVKGAMAATYSALNRNQSPVLEPVGRSTLAQRRGIKKITSTAL
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Nucleus

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 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. 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. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1.
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-577 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-386, allowing binding of PDPK1, which in turn phosphorylates Ser-227 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 193 193 Proton acceptor.
Cross Reference Drug Bank:: DB00945
Gene Ontology Go:: cytoplasm
cytosol
nucleoplasm
ATP binding
cysteine-type endopeptidase inhibitor activity involved in apoptotic process
magnesium ion binding
protein kinase activity
protein serine/threonine kinase activity
axon guidance
cell cycle
central nervous system development
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 transcription from RNA polymerase II promoter
regulation of DNA-templated transcription in response to stress
regulation of translation in response to stress
response to lipopolysaccharide
signal transduction
skeletal system development
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
central nervous system development
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 transcription from RNA polymerase II promoter
regulation of DNA-templated transcription in response to stress
regulation of translation in response to stress
response to lipopolysaccharide
signal transduction
skeletal system development
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 kinase activity
protein serine/threonine kinase activity
Gene Ontology Cellular Component:: cytoplasm
cytosol
nucleoplasm
Keywords:: 3D-structure
ATP-binding
Cell cycle
Complete proteome
Cytoplasm
Disease mutation
Kinase
Magnesium
Mental retardation
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Stress response
Transferase
Interacts With:: P28482

Names & Taxonomy

Structure

Subcellular location

Function

Publication