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

STK3 (Q13188) - Overview - Molecular Target Synopsis

Protein


STK3, Serine/threonine-protein kinase 3
Enzyme Classification 2.7.11.1
UniProt Q13188

Also Known as STK3_HUMAN, STK3, KRS1, MST2

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. Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation (By similarity). Interacts with and stabilizes SAV1 (PubMed:15688006, PubMed:16930133, PubMed:28087714). 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). Interacts with DLG5 (via PDZ domain 3) (PubMed:28087714). Interacts with LATS1; this interaction is inhibited in the presence of DLG5 (PubMed:28087714). Interacts with MARK3 in the presence of DLG5 (PubMed:28087714).

6AR2
5 RESIDUE FRAGMENT OF
ASP-GLY-TPO-MET-LYS-ARG
IN THE STRUCTURE OF
STRUCTURE OF HUMAN SLMAP FHA DOMAIN IN COMPLEX WITH PMST2
RCSB/PDB
Inspect Structure
See all 3D Structures for STK3

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: STK3 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: STK3 is active in the following subcellular-locations: cytoplasm, cytosol, nucleus, protein-containing complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project STK3 has gain in 11 cell-lines, loss in 1 cell-lines and no signal in 993 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: BT_549, NCI_H322M, HS578T

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC1954, MKN-74, CaR-1

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: SK-N-SH, HSMM, HMEC

(see details)

RNA Interference


STK3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CAL51, MDAMB453. (see details)

3D Structures


For STK3 there are:
10 structures (44 chains) solved
3 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


STK3 has been screened with 926 compounds (1576 bioactivities), 22 compounds have bioactivities that show binding affinity of <= 500nM (31 bioactivities). (see details)