- Protein Name
- Mitogen-activated protein kinase 9
- Gene Name
- MAPK9
- Organism
-
Homo sapiens
- 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. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692).
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.
| Site |
Maximum Consensus Site Population |
Minimum Consensus Site Population |
Median Consensus Site Population |
| MT3 |
15 |
7 |
11.5 |
| ATP |
16 |
5 |
12.0 |
| DEF |
6 |
2 |
4.0 |
| CMP |
19 |
12 |
17.0 |
| EDI |
26 |
6 |
16.0 |
| DRS |
13 |
3 |
5.0 |
| PDIG |
15 |
12 |
14.5 |
| PIF |
18 |
16 |
17.0 |
| PDB ID |
Maximum Consensus Site Population |
| MPP site |
AAS site |
MT3 site |
LBP site |
ATP site |
DEF site |
DFG site |
CMP site |
PMP site |
EDI site |
DRS site |
PDIG site |
PIF site |
| Total Druggable Structures per Site |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
1 |
0 |
2 |
0 |
0 |
2 |
|
AFP45984
|
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3E7O
|
0 |
0 |
15 |
0 |
16 |
6 |
0 |
12 |
0 |
21 |
13 |
15 |
18 |
|
3NPC
|
0 |
0 |
12 |
0 |
12 |
2 |
0 |
19 |
0 |
26 |
7 |
15 |
16 |