| Gene |
STK4
|
| Protein Name |
STK4_HUMAN |
| Organism |
Homo sapiens (Human) |
| Alternative name(s) |
Serine/threonine-protein kinase 4 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 1) (MST-1) (STE20-like kinase MST1) (Serine/threonine-protein kinase Krs-2) [Cleaved into: Serine/threonine-protein kinase 4 37kDa subunit (MST1/N); Serine/threonine-protein kinase 4 18kDa subunit (MST1/C)] |
| Protein Family |
Protein kinase superfamily |
| NCBI Gene ID |
6789
|
| UniProt ID |
Q13043
|
| Enzyme Class |
2.7.11.1 |
| Molecular Weight |
55630 |
| Protein Length |
487 |
| Protein Domain |
InterPro |
Pfam
|
| 3D Structure |
PDBe |
PDBj |
RCSB PDB |
DrugPort
ModBase |
SwissModel
|
| Gene Expression |
Gene Expression Atlas
|
| Function and Disease |
OMIM |
| Protein-protein Interaction Database |
STRING |
IntAct |
MINT
|
| Kinase Database |
Phospho.ELM
|
PhosphoSite
| NetworKIN
|
| Catalytic Activity (UniProt annotation) |
ATP + a protein = ADP + a phosphoprotein. |
| Localization |
Cytoplasm. Nucleus. Note=The caspase-cleaved form cycles between the nucleus and cytoplasm. |
| Function (UniProt annotation) |
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. |
| Gene Ontology |
GO:0000287; GO:0000902; GO:0001569; GO:0001841; GO:0001934; GO:0003157; GO:0004672; GO:0004674; GO:0005524; GO:0005634; GO:0005654; GO:0005737; GO:0005829; GO:0006468; GO:0006915; GO:0007165; GO:0007417; GO:0008134; GO:0008285; GO:0016604; GO:0018105; GO:0023014; GO:0030216; GO:0031098; GO:0032092; GO:0032147; GO:0032991; GO:0033138; GO:0035329; GO:0035556; GO:0042802; GO:0042803; GO:0043065; GO:0043539; GO:0045600; GO:0046621; GO:0046777; GO:0046983; GO:0050821; GO:0060215; GO:0060706; GO:0060800; GO:0090090; GO:0097284; GO:1902043; GO:1905461 |
