RPS6KA5 - Ribosomal protein S6 kinase alpha-5 - human protein (Function)
 
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RPS6KA5 »  Ribosomal protein S6 kinase alpha-5   [ EC 2.7.11.1 ]  (S6K-alpha-5)
 
Protein also known as:  Nuclear mitogen- and stress-activated protein kinase 1.
Gene name:  RPS6KA5
Entry whose protein(s) existence is based on evidence at protein level
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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 factors RELA, STAT3 and ETV1/ER81, 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 and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. 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. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury.  
9
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • IDAUniProtKB
Magnesium ion bindingdefinition[GO:0000287] silver  
  • IEAInterPro 2 GO
Protein bindingdefinition[GO:0005515]  
1
  • IPIIntAct
Protein kinase activitydefinition[GO:0004672]  
1
  • IDAUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IMPUniProtKB
GO biological process 
Epidermal growth factor receptor signaling pathwaydefinition[GO:0007173]  
1
  • TASUniProtKB
Histone H2A-S1 phosphorylationdefinition[GO:0043990]  
1
  • IDAUniProtKB
Histone H3-S10 phosphorylationdefinition[GO:0043987]  
1
  • IMPUniProtKB
Histone H3-S28 phosphorylationdefinition[GO:0043988]  
1
  • IMPUniProtKB
Histone phosphorylationdefinition[GO:0016572]  
2
  • TASBHF-UCL
  • IDAUniProtKB
Inflammatory responsedefinition[GO:0006954]  
  • IEAUniProtKB KW
Interleukin-1-mediated signaling pathwaydefinition[GO:0070498]  
1
  • IMPBHF-UCL
Intracellular signal transductiondefinition[GO:0035556]  
1
  • IDAUniProtKB
Negative regulation of cytokine productiondefinition[GO:0001818]  
1
  • TASUniProtKB
Negative regulation of transcription, DNA-templateddefinition[GO:0045892]  
1
  • IDAUniProtKB
Positive regulation of CREB transcription factor activitydefinition[GO:0032793]  
1
  • TASUniProtKB
Positive regulation of histone acetylationdefinition[GO:0035066]  
1
  • IMPBHF-UCL
Positive regulation of histone phosphorylationdefinition[GO:0033129]  
1
  • IMPBHF-UCL
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
2
  • IMPUniProtKB
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • IMPBHF-UCL
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
2
  • IMPUniProtKB
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.  
3
  • CuratedUniProtKB
It requires the following cofactor
Magnesium.  
3
  • CuratedUniProtKB
It is regulated in the following manner
Activated by phosphorylation at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-750, Ser-752 and Ser-758 in its own C-terminal region.  
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  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Bladder cancer  hsa05219+9252  
MAPK signaling pathway  hsa04010+9252  
Neurotrophin signaling pathway  hsa04722+9252  
According to Reactome, this protein belongs to the following pathways:
Developmental Biology  REACT_111045  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
TRAF6 Mediated Induction of proinflammatory cytokines  REACT_6782  
Note 
Enzyme activity requires the presence of both kinase domains.  
1
  • CuratedUniProtKB
 

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: RPS6KA5
GenomeRNAi: 9252
PRO: PR:O75582
Chemistry
GuidetoPHARMACOLOGY: 1523