InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Mapkapk3

Summary

InnateDB Protein

IDBP-197026.6

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; AI874665; MAPKAP-K3; MAPKAP3; MapkKapk3; MK-3; MK3;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000035194

InnateDB Gene

IDBG-197024 (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:17906627, ECO:0000269PubMed:20724476}.

Subcellular Localization

Isoform 1: Nucleus. Cytoplasm. Note=Predominantly located in the nucleus, when activated it translocates to the cytoplasm.Isoform 3: Nucleus. Cytoplasm. Note=Localizes throughout the cell. Degraded in response to osmotic stress.

Disease Associations

Tissue Specificity

Ubiquitously expressed (at protein level). Isoform 3 is expressed in skeletal muscles and heart. {ECO:0000269PubMed:17030606}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.

Experimentally validated
Total	2 [view]
Protein-Protein	1 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	19 [view]

Gene Ontology

Molecular Function

Accession	GO Term
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:0002224	toll-like receptor signaling pathway
GO:0006468	protein phosphorylation
GO:0009103	lipopolysaccharide biosynthetic process
GO:0018105	peptidyl-serine phosphorylation
GO:0032496	response to lipopolysaccharide
GO:0034097	response to cytokine
GO:0044351	macropinocytosis

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0016020	membrane
GO:0031965	nuclear membrane

Protein Structure and Domains

PDB ID

MGI:2143163

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