InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAPK9

Summary

InnateDB Protein

IDBP-382700.4

Last Modified

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

Gene Symbol

MAPK9

Protein Name

mitogen-activated protein kinase 9

Synonyms

JNK-55; JNK2; JNK2A; JNK2ALPHA; JNK2B; JNK2BETA; p54a; p54aSAPK; PRKM9; SAPK; SAPK1a;

Species

Homo sapiens

Ensembl Protein

ENSP00000394560

InnateDB Gene

IDBG-62183 (MAPK9)

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 MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons.MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:19675674}. Nucleus {ECO:0000269PubMed:19675674}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 129 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	129 [view]
Protein-Protein	127 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004705	JUN kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008134	transcription factor binding
GO:0008656	cysteine-type endopeptidase activator activity involved in apoptotic process
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0031435	mitogen-activated protein kinase kinase kinase binding

Biological Process

GO:0001836	release of cytochrome c from mitochondria
GO:0001934	positive regulation of protein phosphorylation
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:0006626	protein targeting to mitochondrion
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006950	response to stress
GO:0007254	JNK cascade
GO:0007258	JUN phosphorylation
GO:0007417	central nervous system development
GO:0009103	lipopolysaccharide biosynthetic process
GO:0009612	response to mechanical stimulus
GO:0009636	response to toxic substance
GO:0010033	response to organic substance
GO:0010628	positive regulation of gene expression
GO:0010744	positive regulation of macrophage derived foam cell differentiation
GO:0010770	positive regulation of cell morphogenesis involved in differentiation
GO:0014075	response to amine
GO:0031175	neuron projection development
GO:0031394	positive regulation of prostaglandin biosynthetic process
GO:0031396	regulation of protein ubiquitination
GO:0032308	positive regulation of prostaglandin secretion
GO:0032722	positive regulation of chemokine production
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:0034644	cellular response to UV
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:0042493	response to drug
GO:0043065	positive regulation of apoptotic process
GO:0043280	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045429	positive regulation of nitric oxide biosynthetic process
GO:0045893	positive regulation of transcription, DNA-templated
GO:0046328	regulation of JNK cascade
GO:0046686	response to cadmium ion
GO:0051090	regulation of sequence-specific DNA binding transcription factor activity
GO:0051403	stress-activated MAPK cascade
GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process
GO:0071222	cellular response to lipopolysaccharide
GO:0071347	cellular response to interleukin-1
GO:0071356	cellular response to tumor necrosis factor
GO:0071363	cellular response to growth factor stimulus
GO:2001235	positive regulation of apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005739	mitochondrion
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