InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Mapk8

Summary

InnateDB Protein

IDBP-257039.6

Last Modified

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

Gene Symbol

Mapk8

Protein Name

mitogen-activated protein kinase 8

Synonyms

AI849689; JNK; JNK1; Prkm8; SAPK1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000107576

InnateDB Gene

IDBG-148417 (Mapk8)

Protein Structure

UniProt Annotation

Function

Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. {ECO:0000250, ECO:0000269PubMed:10811224, ECO:0000269PubMed:11602244, ECO:0000269PubMed:19966288, ECO:0000269PubMed:21297631, ECO:0000269PubMed:9393873}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:16618812}. Nucleus {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 43 experimentally validated interaction(s) in this database.
They are also associated with 139 interaction(s) predicted by orthology.

Experimentally validated
Total	43 [view]
Protein-Protein	43 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	139 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004705	JUN kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0035033	histone deacetylase regulator activity
GO:0042826	histone deacetylase binding

Biological Process

GO:0001503	ossification
GO:0006468	protein phosphorylation
GO:0007254	JNK cascade
GO:0007258	JUN phosphorylation
GO:0009103	lipopolysaccharide biosynthetic process
GO:0009411	response to UV
GO:0010468	regulation of gene expression
GO:0010628	positive regulation of gene expression
GO:0018105	peptidyl-serine phosphorylation
GO:0018107	peptidyl-threonine phosphorylation
GO:0031063	regulation of histone deacetylation
GO:0032091	negative regulation of protein binding
GO:0032880	regulation of protein localization
GO:0043066	negative regulation of apoptotic process
GO:0046686	response to cadmium ion
GO:0048263	determination of dorsal identity
GO:0070301	cellular response to hydrogen peroxide
GO:0071222	cellular response to lipopolysaccharide
GO:0071260	cellular response to mechanical stimulus
GO:0071732	cellular response to nitric oxide
GO:0090045	positive regulation of deacetylase activity
GO:0097300	programmed necrotic cell death
GO:2000017	positive regulation of determination of dorsal identity
GO:2001235	positive regulation of apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005829	cytosol
GO:0016020	membrane

Protein Structure and Domains

PDB ID

MGI:1346861

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR008351 Mitogen-activated protein (MAP) kinase, JNK
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF06293

PRINTS

PR00109
PR01772

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt