ID:MK09_HUMAN DESCRIPTION: RecName: Full=Mitogen-activated protein kinase 9; Short=MAP kinase 9; Short=MAPK 9; EC=2.7.11.24; AltName: Full=JNK-55; AltName: Full=Stress-activated protein kinase 1a; Short=SAPK1a; AltName: Full=Stress-activated protein kinase JNK2; AltName: Full=c-Jun N-terminal kinase 2; 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. FUNCTION: 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. ENZYME REGULATION: Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1. SUBUNIT: Interacts with MECOM and DCLK2 (By similarity). Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP- 2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with NFATC4. Interacts with ATF7; the interaction does not phosphorylate ATF7 but acts as a docking site for ATF7-associated partners such as JUN. Interacts with BCL10. Interacts with CTNNB1 and GSK3B. INTERACTION: P40763:STAT3; NbExp=3; IntAct=EBI-713586, EBI-518675; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. DOMAIN: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. PTM: Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Autophosphorylated in vitro. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/JNK2ID426.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mapk9/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P45984
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006468 protein phosphorylation GO:0007254 JNK cascade GO:0007258 JUN phosphorylation GO:0009612 response to mechanical stimulus GO:0010628 positive regulation of gene expression GO:0010744 positive regulation of macrophage derived foam cell differentiation GO:0016310 phosphorylation GO:0018105 peptidyl-serine phosphorylation GO:0031398 positive regulation of protein ubiquitination GO:0034614 cellular response to reactive oxygen species GO:0038095 Fc-epsilon receptor signaling pathway GO:0042752 regulation of circadian rhythm GO:0043065 positive regulation of apoptotic process GO:0046686 response to cadmium ion GO:0048511 rhythmic process GO:0048666 neuron development GO:0071276 cellular response to cadmium ion GO:0071310 cellular response to organic substance GO:0071803 positive regulation of podosome assembly GO:1901485 positive regulation of transcription factor catabolic process GO:2001235 positive regulation of apoptotic signaling pathway
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
