Tchem STK3 Serine/threonine-protein kinase 3

Protein Summary

Description

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. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38. This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Uniprot Accession IDs

• Q13188
• A8K722
• B3KYA7
• Q15445
• Q15801
• Q96FM6

Gene Name

• STK3

Ensembl ID

• ENST00000419617
• ENSP00000390500
• ENSG00000104375
• ENST00000523601
• ENSP00000429744

Symbol

• KRS1
• MST2
• KRS1
• MST2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
drug perturbation	1
molecular function	1
biological process	0.93
hub protein	0.85
protein domain	0.85

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Ste Group / Ste20 Family / Mst Subfamily / Serine/threonine-protein Kinase 3

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 16.73   (req: < 5)

Gene RIFs: 65   (req: <= 3)

Antibodies: 424   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 16.73   (req: >= 5)

Gene RIFs: 65   (req: > 3)

Antibodies: 424   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 33

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 21

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0