InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RPS6KA5

Summary

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}.

Comments

Interactions

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]
RNA-RNA	0
DNA-RNA	0

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

PDB ID

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
PF07714
PF01636
PF06293
PF00433

PRINTS

PR00109

PIRSF

PIRSF000606

SMART

SM00133
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References