RPS6KA3 - Ribosomal protein S6 kinase alpha-3 - human protein (Function)
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RPS6KA3 »  Ribosomal protein S6 kinase alpha-3   [ EC ]  (S6K-alpha-3)
Protein also known as:  MAP kinase-activated protein kinase 1b (MAPKAPK-1b).
Gene name:  RPS6KA3
Entry whose protein(s) existence is based on evidence at protein level
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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.  
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Cysteine-type endopeptidase inhibitor activity involved in apoptotic processdefinition[GO:0043027]  
  • IDAUniProtKB
Magnesium ion bindingdefinition[GO:0000287] silver  
  • IEAInterPro 2 GO
Protein kinase activitydefinition[GO:0004672]  
Protein kinase bindingdefinition[GO:0019901] silver  
  • IEAOrtholog Compara
Protein serine/threonine kinase activitydefinition[GO:0004674] silver  
  • IEAOrtholog Compara
GO biological process 
Cell cycledefinition[GO:0007049]  
  • IEAUniProtKB KW
Central nervous system developmentdefinition[GO:0007417]  
Negative regulation of apoptotic processdefinition[GO:0043066]  
  • TASUniProtKB
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0043154]  
  • IDAUniProtKB
Positive regulation of cell differentiationdefinition[GO:0045597]  
  • TASUniProtKB
Positive regulation of cell growthdefinition[GO:0030307]  
  • TASUniProtKB
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
Protein phosphorylationdefinition[GO:0006468] silver  
  • IEAInterPro 2 GO
Regulation of DNA-templated transcription in response to stressdefinition[GO:0043620]  
  • TASUniProtKB
Regulation of translation in response to stressdefinition[GO:0043555]  
  • TASUniProtKB
Response to lipopolysaccharidedefinition[GO:0032496]  
  • ISSOrtholog Curator
Signal transductiondefinition[GO:0007165]  
Skeletal system developmentdefinition[GO:0001501]  
Toll-like receptor signaling pathwaydefinition[GO:0002224]  
  • ISSOrtholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium (By similarity).  
  • CuratedUniProtKB
It is regulated in the following manner
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.  
  • CuratedUniProtKB
More information is available from:
According to KEGG, this protein belongs to the following pathways:
Long-term potentiation  hsa04720+6197  
MAPK signaling pathway  hsa04010+6197  
mTOR signaling pathway  hsa04150+6197  
Neurotrophin signaling pathway  hsa04722+6197  
Oocyte meiosis  hsa04114+6197  
Progesterone-mediated oocyte maturation  hsa04914+6197  
According to Reactome, this protein belongs to the following pathways:
CREB phosphorylation  REACT_12524  
CREB phosphorylation through the activation of Ras  REACT_20568  
ERK/MAPK targets  REACT_12599  
Gastrin-CREB signalling pathway via PKC and MAPK  REACT_120966  
Recycling pathway of L1  REACT_22365  
RSK activation  REACT_20510  
Senescence-Associated Secretory Phenotype (SASP)  REACT_169168  


Biological process 
Cell cycle  definition   [KW-0131]
Stress response  definition   [KW-0346]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: RPS6KA3
GenomeRNAi: 6197
PRO: PR:P51812