InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAPKAPK3

Summary

InnateDB Protein

IDBP-378627.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MAPKAPK3

Protein Name

mitogen-activated protein kinase-activated protein kinase 3

Synonyms

3PK; MAPKAP-K3; MAPKAP3; MAPKAPK-3; MK-3;

Species

Homo sapiens

Ensembl Protein

ENSP00000396467

InnateDB Gene

IDBG-37235 (MAPKAPK3)

Protein Structure

UniProt Annotation

Function

Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38- alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. {ECO:0000269PubMed:10383393, ECO:0000269PubMed:15563468, ECO:0000269PubMed:18021073, ECO:0000269PubMed:20599781, ECO:0000269PubMed:8626550, ECO:0000269PubMed:8774846}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:15302577}. Cytoplasm {ECO:0000269PubMed:15302577}. Note=Predominantly located in the nucleus, when activated it translocates to the cytoplasm.

Disease Associations

Tissue Specificity

Widely expressed, with a higher expression level observed in heart and skeletal muscle. No expression in brain. {ECO:0000269PubMed:8622688, ECO:0000269PubMed:8626550}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 32 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	32 [view]
Protein-Protein	31 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004708	MAP kinase 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:0000187	activation of MAPK activity
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:0006468	protein phosphorylation
GO:0006950	response to stress
GO:0007165	signal transduction
GO:0007265	Ras protein signal transduction
GO:0009103	lipopolysaccharide biosynthetic process
GO:0018105	peptidyl-serine phosphorylation
GO:0032496	response to lipopolysaccharide
GO:0034097	response to cytokine
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: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:0044351	macropinocytosis
GO:0045087	innate immune response
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0051403	stress-activated MAPK cascade

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016020	membrane
GO:0031965	nuclear membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF06293

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt