Background: | 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. |
Synonyms: | Serine/threonine-protein kinase 3 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 2) (MST-2) (STE20-like kinase MST2) (Serine/threonine-protein kinase Krs-1) [Cleaved into: Serine/threonine-protein kinase 3 36kDa subunit (MST2/N); Serine/threonine-protein kinase 3 20kDa subunit (MST2/C)], STK3, KRS1 MST2 |
UniProt Protein Function: | MST2: a protein kinase of the STE20 family. Activated by apoptotic signals as well as other stress conditions. Full activation requires both phosphorylation and caspase-mediated cleavage. Following cleavage by caspase-3, undergoes irreversible autophosphorylation. Full-length is mainly unphosphorylated in the rat thymus and cultured cells, whereas caspase-3-cleaved MST2 in apoptotic cells is highly phosphorylated. |
UniProt Protein Details: | Protein type:Protein kinase, STE; Protein kinase, Ser/Thr (non-receptor); Kinase, protein; Autophagy; EC 2.7.11.1; STE group; STE20 family; MST subfamily Chromosomal Location of Human Ortholog: 8q22.2 Cellular Component: cytoplasm; cytosol; nucleus Molecular Function:protein dimerization activity; protein serine/threonine kinase activity; protein serine/threonine kinase activator activity; protein binding; magnesium ion binding; ATP binding; receptor signaling protein serine/threonine kinase activity; protein kinase activity Biological Process: central nervous system development; positive regulation of protein binding; protein stabilization; positive regulation of apoptosis; apoptosis; positive regulation of JNK cascade; signal transduction; negative regulation of organ growth; protein amino acid phosphorylation; negative regulation of cell proliferation; positive regulation of protein kinase B signaling cascade; positive regulation of fat cell differentiation; positive regulation of transcription factor activity; neural tube formation |
NCBI Summary: | 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 Code: | Q13188 |
NCBI GenInfo Identifier: | 46577700 |
NCBI Gene ID: | 6788 |
NCBI Accession: | Q13188.2 |
UniProt Secondary Accession: | Q13188,Q15445, Q15801, Q96FM6, A8K722, B3KYA7, |
UniProt Related Accession: | Q13188 |
Molecular Weight: | 491 |
NCBI Full Name: | Serine/threonine-protein kinase 3 |
NCBI Synonym Full Names: | serine/threonine kinase 3 |
NCBI Official Symbol: | STK3 |
NCBI Official Synonym Symbols: | KRS1; MST2 |
NCBI Protein Information: | serine/threonine-protein kinase 3; MST-2; STE20-like kinase MST2; mammalian STE20-like protein kinase 2; serine/threonine-protein kinase Krs-1; serine/threonine kinase 3 (STE20 homolog, yeast); serine/threonine kinase 3 (Ste20, yeast homolog) |
UniProt Protein Name: | Serine/threonine-protein kinase 3 |
UniProt Synonym Protein Names: | Mammalian STE20-like protein kinase 2; MST-2; STE20-like kinase MST2; Serine/threonine-protein kinase Krs-1Cleaved into the following 2 chains:Serine/threonine-protein kinase 3 36kDa subunit; MST2/N; Serine/threonine-protein kinase 3 20kDa subunit; MST2/C |
Protein Family: | Serine/threonine-protein kinase |
UniProt Gene Name: | STK3 |
UniProt Entry Name: | STK3_HUMAN |