InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAPK8

Summary

InnateDB Protein

IDBP-73487.6

Last Modified

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

Gene Symbol

MAPK8

Protein Name

mitogen-activated protein kinase 8

Synonyms

JNK; JNK-46; JNK1; JNK1A2; JNK21B1/2; PRKM8; SAPK1; SAPK1c;

Species

Homo sapiens

Ensembl Protein

ENSP00000353483

InnateDB Gene

IDBG-73479 (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. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH.JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta- 2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:21148294}. Nucleus {ECO:0000269PubMed:21148294}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 259 experimentally validated interaction(s) in this database.
They are also associated with 23 interaction(s) predicted by orthology.

Experimentally validated
Total	259 [view]
Protein-Protein	255 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	23 [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: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: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:0006915	apoptotic process
GO:0006950	response to stress
GO:0007254	JNK cascade
GO:0007258	JUN phosphorylation
GO:0009103	lipopolysaccharide biosynthetic process
GO:0009411	response to UV
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: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:0038095	Fc-epsilon receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0051090	regulation of sequence-specific DNA binding transcription factor activity
GO:0051403	stress-activated MAPK cascade
GO:0071222	cellular response to lipopolysaccharide
GO:0071260	cellular response to mechanical stimulus
GO:0090045	positive regulation of deacetylase activity
GO:0097190	apoptotic signaling pathway
GO:0097193	intrinsic apoptotic signaling pathway
GO:1900740	positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005829	cytosol
GO:0016020	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
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