Homo sapiens Protein: RPS6KA5
InnateDB Protein IDBP-16086.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol RPS6KA5
Protein Name ribosomal protein S6 kinase, 90kDa, polypeptide 5
Synonyms MSK1; MSPK1; RLPK;
Species Homo sapiens
Ensembl Protein ENSP00000261991
InnateDB Gene IDBG-16084 (RPS6KA5)
Protein Structure
UniProt Annotation
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 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. {ECO:0000269PubMed:11909979, ECO:0000269PubMed:12569367, ECO:0000269PubMed:12628924, ECO:0000269PubMed:12763138, ECO:0000269PubMed:12773393, ECO:0000269PubMed:15010469, ECO:0000269PubMed:18511904, ECO:0000269PubMed:9687510, ECO:0000269PubMed:9873047}.
Subcellular Localization Nucleus. Cytoplasm. Note=Predominantly nuclear. Exported into cytoplasm in response to glucocorticoid.
Disease Associations
Tissue Specificity Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver. {ECO:0000269PubMed:9687510, ECO:0000269PubMed:9873047}.
Number of Interactions This gene and/or its encoded proteins are associated with 80 experimentally validated interaction(s) in this database.
Experimentally validated
Total 80 [view]
Protein-Protein 72 [view]
Protein-DNA 5 [view]
Protein-RNA 0
DNA-DNA 3 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000287 magnesium ion binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0016773 phosphotransferase activity, alcohol group as acceptor
Biological Process
GO:0001818 negative regulation of cytokine production
GO:0002224 toll-like receptor signaling pathway
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006355 regulation of transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0006954 inflammatory response
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007411 axon guidance
GO:0009103 lipopolysaccharide biosynthetic process
GO:0016572 histone phosphorylation
GO:0032793 positive regulation of CREB transcription factor activity
GO:0033129 positive regulation of histone phosphorylation
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034146 toll-like receptor 5 signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034166 toll-like receptor 10 signaling pathway
GO:0035066 positive regulation of histone acetylation
GO:0035556 intracellular signal transduction
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0043987 histone H3-S10 phosphorylation
GO:0043988 histone H3-S28 phosphorylation
GO:0043990 histone H2A-S1 phosphorylation
GO:0045087 innate immune response (InnateDB)
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051403 stress-activated MAPK cascade
GO:0070498 interleukin-1-mediated signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0016020 membrane
Protein Structure and Domains
InterPro IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR002575 Aminoglycoside phosphotransferase
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR016239 Ribosomal protein S6 kinase II
IPR017892 Protein kinase, C-terminal
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF00069
Post-translational Modifications
SwissProt O75582
PhosphoSite PhosphoSite-O75582
UniProt Splice Variant
Entrez Gene 9252
UniGene Hs.733807
OMIM 603607
HPRD 06789
EMBL AF074393 AF080000 AF090421 AL121784 AL133454 AL159191 BC017187
GenPept AAC31171 AAC69577 AAD23915 AAH17187