Mitogen-activated protein kinase 9
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.
Database | Links |
---|---|
UniProt | P45984 |
PDB | 3E7O, 3NPC |
BioGrid | 111587 |
BindingDB | P45984 |
DrugBank | Not available |
Guide to PHARMACOLOGY | 1497 |
PharmGKB | PA30630 |
KEGG | hsa:5601 |
BioCyc | Not available |
Entrez Gene (GeneID) | 5601 |
Metric | Mean Value | Standard Deviation |
---|---|---|
AUC | 0.9311 | 0.0026 |
Accuracy | 0.869 | 0.0048 |
Sensitivity | 0.8278 | 0.011 |
Specificity | 0.9034 | 0.0042 |
BEDROC | 0.9911 | 0.0029 |
MCC Threshold | 0.57 | N/A |
MCC | 0.7377 | N/A |
F-score Threshold | 0.494 | N/A |
F-score | 0.8526 | N/A |