Names & Taxonomy

Uniprot ID:
O75676
Entry Name:
KS6A4_HUMAN
Status:
reviewed
Protein Names:
Ribosomal protein S6 kinase alpha-4 (S6K-alpha-4) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 4) (Nuclear mitogen- and stress-activated protein kinase 2) (Ribosomal protein kinase B) (RSKB)
Gene Names:
RPS6KA4 MSK2
Gene Names Primary:
RPS6KA4
Organism:
Homo sapiens (Human)

Structure

Length:
772
Sequence:
MGDEDDDESCAVELRITEANLTGHEEKVSVENFELLKVLGTGAYGKVFLVRKAGGHDAGKLYAMKVLRKAALVQRAKTQEHTRTERSVLELVRQAPFLVTLHYAFQTDAKLHLILDYVSGGEMFTHLYQRQYFKEAEVRVYGGEIVLALEHLHKLGIIYRDLKLENVLLDSEGHIVLTDFGLSKEFLTEEKERTFSFCGTIEYMAPEIIRSKTGHGKAVDWWSLGILLFELLTGASPFTLEGERNTQAEVSRRILKCSPPFPPRIGPVAQDLLQRLLCKDPKKRLGAGPQGAQEVRNHPFFQGLDWVALAARKIPAPFRPQIRSELDVGNFAEEFTRLEPVYSPPGSPPPGDPRIFQGYSFVAPSILFDHNNAVMTDGLEAPGAGDRPGRAAVARSAMMQDSPFFQQYELDLREPALGQGSFSVCRRCRQRQSGQEFAVKILSRRLEANTQREVAALRLCQSHPNVVNLHEVHHDQLHTYLVLELLRGGELLEHIRKKRHFSESEASQILRSLVSAVSFMHEEAGVVHRDLKPENILYADDTPGAPVKIIDFGFARLRPQSPGVPMQTPCFTLQYAAPELLAQQGYDESCDLWSLGVILYMMLSGQVPFQGASGQGGQSQAAEIMCKIREGRFSLDGEAWQGVSEEAKELVRGLLTVDPAKRLKLEGLRGSSWLQDGSARSSPPLRTPDVLESSGPAVRSGLNATFMAFNRGKREGFFLKSVENAPLAKRRKQKLRSATASRRGSPAPANPGRAPVASKGAPRRANGPLPPS
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Nucleus

Function

Function:
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.
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Cofactor:
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation:
ENZYME REGULATION: 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.
Active Site:
ACT_SITE 161 161 Proton acceptor.
Gene Ontology Go:
cytoplasm
nucleoplasm
nucleus
ATP binding
histone kinase activity (H3-S10 specific)
magnesium ion binding
mitogen-activated protein kinase p38 binding
protein serine/threonine kinase activity
ribosomal protein S6 kinase activity
axon guidance
histone H3-S10 phosphorylation
histone H3-S28 phosphorylation
histone phosphorylation
inflammatory response
interleukin-1-mediated signaling pathway
intracellular signal transduction
negative regulation of cytokine production
positive regulation of CREB transcription factor activity
positive regulation of histone acetylation
positive regulation of histone phosphorylation
positive regulation of NF-kappaB transcription factor activity
positive regulation of transcription from RNA polymerase II promoter
protein phosphorylation
regulation of transcription, DNA-templated
Gene Ontology Biological Process:
axon guidance
histone H3-S10 phosphorylation
histone H3-S28 phosphorylation
histone phosphorylation
inflammatory response
interleukin-1-mediated signaling pathway
intracellular signal transduction
negative regulation of cytokine production
positive regulation of CREB transcription factor activity
positive regulation of histone acetylation
positive regulation of histone phosphorylation
positive regulation of NF-kappaB transcription factor activity
positive regulation of transcription from RNA polymerase II promoter
protein phosphorylation
regulation of transcription, DNA-templated
Gene Ontology Molecular Function:
ATP binding
histone kinase activity (H3-S10 specific)
magnesium ion binding
mitogen-activated protein kinase p38 binding
protein serine/threonine kinase activity
ribosomal protein S6 kinase activity
Gene Ontology Cellular Component:
cytoplasm
nucleoplasm
nucleus
Keywords:
ATP-binding
Alternative splicing
Complete proteome
Inflammatory response
Kinase
Magnesium
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Stress response
Transferase
Interacts With:
Q16539

Publication

PubMed ID:
9792677 14702039 9687510 11035004 12773393 18508628 18691976 18669648 19369195 19464896 20068231 22814378 24275569 17344846