STK4
UniProt ID: Q13043
Entrez ID: 6789
Protein name: 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)]
External links: UniprotKB HGNC RefSeq COSMIC
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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 suppressio...
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 (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. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}.
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GO - Biological processes (BP):
apoptotic process [GO:0006915]; branching involved in blood vessel morphogenesis [GO:0001569]; cell differentiation involved in embryonic placenta development [GO:0060706]; cell morphogenesis [GO:0000902]; central nervous system development [GO:0007417]; endocardium development [GO:0003157]; hepatoc...
apoptotic process [GO:0006915]; branching involved in blood vessel morphogenesis [GO:0001569]; cell differentiation involved in embryonic placenta development [GO:0060706]; cell morphogenesis [GO:0000902]; central nervous system development [GO:0007417]; endocardium development [GO:0003157]; hepatocyte apoptotic process [GO:0097284]; hippo signaling [GO:0035329]; intracellular signal transduction [GO:0035556]; keratinocyte differentiation [GO:0030216]; negative regulation of canonical Wnt signaling pathway [GO:0090090]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of organ growth [GO:0046621]; neural tube formation [GO:0001841]; peptidyl-serine phosphorylation [GO:0018105]; positive regulation of apoptotic process [GO:0043065]; positive regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902043]; positive regulation of fat cell differentiation [GO:0045600]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of protein binding [GO:0032092]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of substrate-dependent cell migration, cell attachment to substrate [GO:1904237]; primitive hemopoiesis [GO:0060215]; protein autophosphorylation [GO:0046777]; protein import into nucleus [GO:0006606]; protein phosphorylation [GO:0006468]; protein stabilization [GO:0050821]; protein tetramerization [GO:0051262]; regulation of cell differentiation involved in embryonic placenta development [GO:0060800]; regulation of MAPK cascade [GO:0043408]; signal transduction [GO:0007165]
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GO - Molecular function (MF):
ATP binding [GO:0005524]; identical protein binding [GO:0042802]; magnesium ion binding [GO:0000287]; protein homodimerization activity [GO:0042803]; protein kinase activity [GO:0004672]; protein serine/threonine/tyrosine kinase activity [GO:0004712]; protein serine/threonine kinase activator activi...
ATP binding [GO:0005524]; identical protein binding [GO:0042802]; magnesium ion binding [GO:0000287]; protein homodimerization activity [GO:0042803]; protein kinase activity [GO:0004672]; protein serine/threonine/tyrosine kinase activity [GO:0004712]; protein serine/threonine kinase activator activity [GO:0043539]; protein serine/threonine kinase activity [GO:0004674]; protein serine kinase activity [GO:0106310]; RNA polymerase II-specific DNA-binding transcription factor binding [GO:0061629]
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GO - Cellular component (CC):
cytoplasm [GO:0005737]; cytosol [GO:0005829]; nuclear body [GO:0016604]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]...
cytoplasm [GO:0005737]; cytosol [GO:0005829]; nuclear body [GO:0016604]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]
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STK4
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*NOTE: the Kaplan plots were collected from OncoLnc