- Protein Name
- Mitogen-activated protein kinase kinase kinase 8
- Gene Name
- MAP3K8
- Organism
-
Homo sapiens
- Function
- Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.
| Site |
Maximum Consensus Site Population |
Minimum Consensus Site Population |
Median Consensus Site Population |
| MPP |
17 |
17 |
17.0 |
| PIF |
11 |
11 |
11.0 |
| DRS |
11 |
10 |
10.5 |
| MT3 |
3 |
3 |
3.0 |
| ATP |
16 |
5 |
10.5 |
| PDB ID |
Maximum Consensus Site Population |
| MPP site |
DFG site |
PIF site |
DRS site |
DEF site |
EDI site |
MT3 site |
AAS site |
LBP site |
CMP site |
PDIG site |
ATP site |
PMP site |
| Total Druggable Structures per Site |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
|
4Y85
|
17 |
0 |
11 |
11 |
0 |
0 |
3 |
0 |
0 |
0 |
0 |
16 |
0 |
|
4Y83
|
17 |
0 |
0 |
10 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
16 |
0 |