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Details on Person UniProt:Q13043-1 STK4
| Class:Id | ReferenceIsoform:405555 |
|---|---|
| _chainChangeLog | chain:1-487 added on Fri February 6 2015;chain:1-326 added on Fri February 6 2015;chain:327-487 added on Fri February 6 2015 |
| _displayName | UniProt:Q13043-1 STK4 |
| _timestamp | 2025-02-21 18:52:11 |
| chain | chain:1-487 chain:1-326 chain:327-487 |
| checksum | 150758EBC5F77D5C |
| comment | 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.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)COFACTOR Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-183. Activated by RASSF1 which acts by preventing its dephosphorylation.SUBUNIT Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation. Interacts with and stabilizes SAV1. Interacts with RASSF1. Interacts with FOXO3. Interacts with RASSF2 (via SARAH domain). Interacts with AR, PKB/AKT1, TNNI3 and SIRT1. Interacts with DLG5 (via PDZ domain 3). Interacts with MARK3 in the presence of DLG5 (PubMed:28087714). Interacts with SCRIB in the presence of DLG5 (PubMed:28169360).INTERACTION The caspase-cleaved form cycles between the nucleus and cytoplasm.ALTERNATIVE PRODUCTS Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Ubiquitously expressed.INDUCTION Activity increases during mitosis.PTM Autophosphorylated on serine and threonine residues. Phosphorylation at Thr-387 by PKB/AKT1, leads to inhibition of its: kinase activity, nuclear translocation and autophosphorylation at Thr-183. It also diminishes its cleavage by caspases and its ability to phosphorylate FOXO3.PTM Proteolytically cleaved by caspase-3 during apoptosis at Asp-326 and Asp-349 resulting in a 37 kDa or a 39 kDa subunit respectively. The 39 kDa subunit is further cleaved into the 37 kDa form. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N). It is less likely that cleavage at Asp-349 is a prerequisite for activation as this site is not conserved in the murine ortholog.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.CAUTION Was originally thought to be phosphorylated at Thr-120 (PubMed:19940129). However, this work has been retracted (PubMed:27825096).SEQUENCE CAUTION Contaminating sequence. Potential poly-A sequence.SEQUENCE CAUTION Contaminating sequence. Potential poly-A sequence. |
| created | [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 |
| description | recommendedName: Serine/threonine-protein kinase 4 ecNumber evidence="17"2.7.11.1 alternativeName: Mammalian STE20-like protein kinase 1 shortName: MST-1 alternativeName: STE20-like kinase MST1 alternativeName: Serine/threonine-protein kinase Krs-2 component recommendedName: Serine/threonine-protein kinase 4 37kDa subunit shortName: MST1/N /component component recommendedName: Serine/threonine-protein kinase 4 18kDa subunit shortName: MST1/C /component |
| geneName | STK4 KRS2 MST1 |
| identifier | Q13043 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Apoptosis ATP-binding Coiled coil Cytoplasm Direct protein sequencing Kinase Magnesium Metal-binding Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Transferase |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | STK4 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8991004] ENSEMBL:ENSG00000101109 STK4 [Homo sapiens] |
| secondaryIdentifier | STK4_HUMAN B2RCR8 Q15802 Q4G156 Q5H982 Q6PD60 Q9BR32 Q9NTZ4 |
| sequenceLength | 487 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | Q13043-1 |
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No pathways have been reviewed or authored by UniProt:Q13043-1 STK4 (405555)
