Protein: 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)] (Q13188)
Organism: Homo sapiens (Human)
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. 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.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:29063833}. Nucleus {ECO:0000269|PubMed:21145499}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:37739411}. Note=The caspase-cleaved form cycles between nucleus and cytoplasm (PubMed:11278283, PubMed:19525978). Phosphorylation at Thr-117 leads to inhibition of nuclear translocation (PubMed:19525978). {ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:19525978}.
Sequence: MEQPPAPKSKLKKLSEDSLTKQPEEVFDVLEKLGEGSYGSVFKAIHKESGQVVAIKQVPVESDLQEIIKEISIMQQCDSPYVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLIEDEIATILKSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVKKCLVKNPEQRATATQLLQHPFIKNAKPVSILRDLITEAMEIKAKRHEEQQRELEEEEENSDEDELDSHTMVKTSVESVGTMRATSTMSEGAQTMIEHNSTMLESDLGTMVINSEDEEEEDGTMKRNATSPQVQRPSFMDYFDKQDFKNKSHENCNQNMHEPFPMSKNVFPDNWKVPQDGDFDFLKNLSLEELQMRLKALDPMMEREIEELRQRYTAKRQPILDAMDAKKRRQQNF
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [24-287]
- IPR024205: Mst1/2 SARAH domain (domain) [437-484]
- IPR011524: SARAH domain (domain) [437-484]
- IPR050629: STE20/SPS1-related Proline-Alanine-rich Kinase (family) [18-412]
- IPR049568: Mst2, SARAH domain (domain) [436-484]
- IPR017441: Protein kinase, ATP binding site (binding_site) [33-56]
- IPR000719: Protein kinase domain (domain) [27-278]
- IPR036674: p53-like tetramerisation domain superfamily (homologous_superfamily) [435-491]
Interaction partners: - Protein salvador homolog 1
- MOB kinase activator 1A
- Ras association domain-containing protein 1
- Ras association domain-containing protein 2
- Serine/threonine-protein kinase LATS1
- Serine/threonine-protein kinase 4
- Ras association domain-containing protein 4
- Ras association domain-containing protein 6
- Serine/threonine-protein kinase LATS2
- MOB kinase activator 1B
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0050794 (regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0010942 (positive regulation of cell death), GO:0010941 (regulation of cell death), GO:0043067 (regulation of programmed cell death), GO:0043068 (positive regulation of programmed cell death), GO:0043065 (positive regulation of apoptotic process), GO:0042981 (regulation of apoptotic process), GO:0010661 (positive regulation of muscle cell apoptotic process), GO:0010660 (regulation of muscle cell apoptotic process), GO:0034391 (regulation of smooth muscle cell apoptotic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0016604 (nuclear body), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)