ID:STK3_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase 3; EC=2.7.11.1; AltName: Full=Mammalian STE20-like protein kinase 2; Short=MST-2; AltName: Full=STE20-like kinase MST2; AltName: Full=Serine/threonine-protein kinase Krs-1; Contains: RecName: Full=Serine/threonine-protein kinase 3 36kDa subunit; Short=MST2/N; Contains: RecName: Full=Serine/threonine-protein kinase 3 20kDa subunit; Short=MST2/C; 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. ENZYME REGULATION: Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-180, which are inhibited by the proto-oncogene product RAF1. Activated by RASSF1 which acts by preventing its dephosphorylation. SUBUNIT: Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation (By similarity). Interacts with and stabilizes SAV1. Interacts with RAF1, which prevents dimerization and phosphorylation. Interacts with RASSF1. Interacts (via SARAH domain) with isoform 1 of NEK2. Interacts with ESR1 only in the presence of SAV1. Interacts with PKB/AKT1. Forms a tripartite complex with MOBKL1B and STK38. Interacts with RASSF2 (via SARAH domain). INTERACTION: O95166:GABARAP; NbExp=2; IntAct=EBI-992580, EBI-712001; Q9H0R8:GABARAPL1; NbExp=2; IntAct=EBI-992580, EBI-746969; P60520:GABARAPL2; NbExp=2; IntAct=EBI-992580, EBI-720116; Q9GZQ8:MAP1LC3B; NbExp=5; IntAct=EBI-992580, EBI-373144; Q9BXW4:MAP1LC3C; NbExp=2; IntAct=EBI-992580, EBI-2603996; Q9NS23-2:RASSF1; NbExp=3; IntAct=EBI-992580, EBI-438698; Q8WWW0:RASSF5; NbExp=2; IntAct=EBI-992580, EBI-367390; Q9H4B6:SAV1; NbExp=6; IntAct=EBI-992580, EBI-1017775; Q13043:STK4; NbExp=3; IntAct=EBI-992580, EBI-367376; SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). Note=The caspase-cleaved form cycles between nucleus and cytoplasm (By similarity). Phosphorylation at Thr-117 leads to inhibition of nuclear translocation. TISSUE SPECIFICITY: Expressed at high levels in adult kidney, skeletal and placenta tissues and at very low levels in adult heart, lung and brain tissues. INDUCTION: Activity increases during mitosis. PTM: Phosphorylation at Thr-117 and Thr-384 by PKB/AKT1, leads to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation, and increase in its binding to RAF1. PTM: Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N). SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SARAH domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF03109 - ABC1 atypical kinase-like domain PF07714 - Protein tyrosine and serine/threonine kinase PF11629 - C terminal SARAH domain of Mst1 PF17667 - Fungal protein kinase
SCOP Domains: 48371 - ARM repeat 56112 - Protein kinase-like (PK-like) 143113 - NAP-like
ModBase Predicted Comparative 3D Structure on Q13188
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001841 neural tube formation GO:0003157 endocardium development GO:0006468 protein phosphorylation GO:0006915 apoptotic process GO:0007165 signal transduction GO:0007346 regulation of mitotic cell cycle GO:0007417 central nervous system development GO:0008285 negative regulation of cell proliferation GO:0016310 phosphorylation GO:0023014 signal transduction by protein phosphorylation GO:0031098 stress-activated protein kinase signaling cascade GO:0032092 positive regulation of protein binding GO:0035329 hippo signaling GO:0035556 intracellular signal transduction GO:0042981 regulation of apoptotic process GO:0043065 positive regulation of apoptotic process GO:0045600 positive regulation of fat cell differentiation GO:0046330 positive regulation of JNK cascade GO:0046621 negative regulation of organ growth GO:0050821 protein stabilization GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051897 positive regulation of protein kinase B signaling GO:0060215 primitive hemopoiesis GO:0060706 cell differentiation involved in embryonic placenta development GO:0060800 regulation of cell differentiation involved in embryonic placenta development GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0090090 negative regulation of canonical Wnt signaling pathway GO:0097284 hepatocyte apoptotic process GO:1902043 positive regulation of extrinsic apoptotic signaling pathway via death domain receptors
BC010640 - Homo sapiens serine/threonine kinase 3 (STE20 homolog, yeast), mRNA (cDNA clone MGC:17710 IMAGE:3868822), complete cds. GQ891419 - Homo sapiens clone HEL-S-140 epididymis secretory sperm binding protein mRNA, complete cds. AK131363 - Homo sapiens cDNA FLJ16404 fis, clone UTERU2008019, highly similar to Serine/threonine-protein kinase 3 (EC 2.7.11.1). U26424 - Human Ste20-like kinase (MST2) mRNA, complete cds. U60206 - Homo sapiens serine/threonine protein kinase Krs-1 mRNA, complete cds. AK291837 - Homo sapiens cDNA FLJ77336 complete cds, highly similar to Homo sapiens serine/threonine kinase 3 (STE20 homolog, yeast) (STK3), mRNA. AK312660 - Homo sapiens cDNA, FLJ93050. KJ897618 - Synthetic construct Homo sapiens clone ccsbBroadEn_07012 STK3 gene, encodes complete protein. KJ905323 - Synthetic construct Homo sapiens clone ccsbBroadEn_14850 STK3 gene, encodes complete protein. AK307787 - Homo sapiens cDNA, FLJ97735. AK075229 - Homo sapiens cDNA FLJ90748 fis, clone PLACE1011824, highly similar to Human Ste20-like kinase (MST2) mRNA. CU679773 - Synthetic construct Homo sapiens gateway clone IMAGE:100019646 5' read STK3 mRNA. Z25422 - H.sapiens protein-serine/threonine kinase gene, complete CDS. AB528979 - Synthetic construct DNA, clone: pF1KE0903, Homo sapiens STK3 gene for serine/threonine kinase 3, without stop codon, in Flexi system. JD093892 - Sequence 74916 from Patent EP1572962. JD280467 - Sequence 261491 from Patent EP1572962. JD245814 - Sequence 226838 from Patent EP1572962. JD501985 - Sequence 483009 from Patent EP1572962. JD553358 - Sequence 534382 from Patent EP1572962. JD304863 - Sequence 285887 from Patent EP1572962. JD296793 - Sequence 277817 from Patent EP1572962. JD273224 - Sequence 254248 from Patent EP1572962. JD504544 - Sequence 485568 from Patent EP1572962. JD487952 - Sequence 468976 from Patent EP1572962. JD378562 - Sequence 359586 from Patent EP1572962. JD139300 - Sequence 120324 from Patent EP1572962. JD226823 - Sequence 207847 from Patent EP1572962. JD129576 - Sequence 110600 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q13188 (Reactome details) participates in the following event(s):
R-HSA-2028697 Cleavage of p-STK3 (p-MST2) by caspase 3 R-HSA-2028591 Phosphorylation of STK3 (MST2) and SAV1 by STK3 R-HSA-2028589 Phosphorylation of LATS1 and 2 by p-STK3 (p-MST2) R-HSA-2028635 Phosphorylation of MOB1A and B by p-STK3 (p-MST2) R-HSA-2028673 Phosphorylation of LATS1 and 2 by p-STK3 (MST2)/N R-HSA-2028675 Phosphorylation of MOB1A and B by p-STK3(MST2)/N R-HSA-2028269 Signaling by Hippo R-HSA-162582 Signal Transduction
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
