RPS6KA4 - Ribosomal protein S6 kinase alpha-4 - human protein (Function)
 
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RPS6KA4 »  Ribosomal protein S6 kinase alpha-4   [ EC 2.7.11.1 ]  (S6K-alpha-4)
 
Protein also known as:  Nuclear mitogen- and stress-activated protein kinase 2.
Gene name:  RPS6KA4
Entry whose protein(s) existence is based on evidence at protein level
extend overview
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GENE REF ISO

Function

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Overview 
Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors.  
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  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB
Histone kinase activity (H3-S10 specific)definition[GO:0035175]  
1
  • RefGenome
Magnesium ion bindingdefinition[GO:0000287] silver  
1
  • InterPro 2 GO
Mitogen-activated protein kinase p38 bindingdefinition[GO:0048273]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
2
  • IntAct
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • UniProtKB
Ribosomal protein S6 kinase activitydefinition[GO:0004711]  
1
  • UniProtKB
GO biological process 
Histone H3-S10 phosphorylationdefinition[GO:0043987]  
1
  • UniProtKB
Histone H3-S28 phosphorylationdefinition[GO:0043988]  
1
  • UniProtKB
Histone phosphorylationdefinition[GO:0016572]  
1
  • BHF-UCL
Inflammatory responsedefinition[GO:0006954]  
1
  • UniProtKB KW
Interleukin-1-mediated signaling pathwaydefinition[GO:0070498]  
1
  • BHF-UCL
Intracellular signal transductiondefinition[GO:0035556]  
1
  • UniProtKB
Negative regulation of cytokine productiondefinition[GO:0001818]  
1
  • UniProtKB
Positive regulation of CREB transcription factor activitydefinition[GO:0032793]  
1
  • UniProtKB
Positive regulation of histone acetylationdefinition[GO:0035066]  
1
  • BHF-UCL
Positive regulation of histone phosphorylationdefinition[GO:0033129]  
1
  • BHF-UCL
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
1
  • UniProtKB
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • BHF-UCL
Protein phosphorylationdefinition[GO:0006468]  
1
  • UniProtKB
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
1
  • UniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
2
  • UniProtKB
It requires the following cofactor
 Mg(2+)  
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  • UniProtKB
It is regulated in the following manner
Activated by phosphorylation at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-196, Ser-360 and Ser-365 by the activated C-terminal kinase domain.  
1
  • UniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
MAPK signaling pathway  hsa04010+8986  
Neurotrophin signaling pathway  hsa04722+8986  
According to Reactome, this protein belongs to the following pathway:
Recycling pathway of L1  REACT_22365  
Note 
Enzyme activity requires the presence of both kinase domains.  
2
  • UniProtKB
 

Keywords

Biological process 
Inflammatory response  definition   [KW-0395]
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

Other
GeneWiki: RPS6KA4
GenomeRNAi: 8986
PRO: PR:O75676
Chemistry
GuidetoPHARMACOLOGY: 1524