Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

STK4 (Q13043) - Overview - Molecular Target Synopsis

Protein


STK4, Serine/threonine-protein kinase 4
Enzyme Classification 2.7.11.1
UniProt Q13043

Also Known as STK4_HUMAN, STK4, KRS2, MST1

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. 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).

5TWG
4 RESIDUE FRAGMENT OF
T353 PEPTIDE
IN THE STRUCTURE OF
HUMAN MOB1A BOUND TO HUMAN MST1 PHOSPHORYLATED T353 PEPTIDE
RCSB/PDB
Inspect Structure
See all 3D Structures for STK4

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: STK4 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: STK4 is active in the following subcellular-locations: cytoplasm, cytosol, nuclear body, nucleoplasm, nucleus, protein-containing complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project STK4 has gain in 12 cell-lines, loss in 0 cell-lines and no signal in 993 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MDA_MB_435, OVCAR_8, CCRF_CEM

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: RC-K8, MOLP-8, OCI-LY-3

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, SK-N-SH, HeLa-S3

(see details)

RNA Interference


STK4 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CROE33, SCC90. (see details)

3D Structures


For STK4 there are:
6 structures (15 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


STK4 has been screened with 1016 compounds (1771 bioactivities), 22 compounds have bioactivities that show binding affinity of <= 500nM (37 bioactivities). (see details)