Homo sapiens Protein: MAPK9
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
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]
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
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
Post-translational Modifications
SwissProt P45984
PhosphoSite PhosphoSite-P45984
UniProt Splice Variant
Entrez Gene 5601
UniGene Hs.694868
RefSeq NP_002743
OMIM 602896
HPRD 04206
EMBL AB451302 AB451355 AC008610 AC104115 AK289638 BC032539 CH471165 CR536580 DQ066599 EU927388 L31951 U09759 U34821 U35002 U35003
GenPept AAA56831 AAA74740 AAC50606 AAC50608 AAC50609 AAH32539 AAY46156 ACH57450 BAF82327 BAG70116 BAG70169 CAG38817 EAW53757 EAW53758 EAW53759 EAW53762