- Protein Name
- Serine/threonine-protein kinase 4 37kDa subunit
- Gene Name
- STK4
- Organism
-
Homo sapiens
- Function
- Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.
| Site |
Maximum Consensus Site Population |
Minimum Consensus Site Population |
Median Consensus Site Population |
| MPP |
31 |
11 |
19.0 |
| MT3 |
5 |
5 |
5.0 |
| ATP |
19 |
7 |
13.0 |
| DFG |
2 |
2 |
2.0 |
| CMP |
6 |
2 |
3.5 |
| PDIG |
16 |
10 |
16.0 |
| PIF |
31 |
25 |
28.0 |
| 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 |
2 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
1 |
|
AFQ13043
|
31 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
16 |
0 |
|
3COM
|
22 |
0 |
5 |
0 |
19 |
0 |
2 |
6 |
0 |
0 |
0 |
16 |
31 |