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

LATS2 (Q9NRM7) - Overview - Molecular Target Synopsis

Protein


LATS2, Serine/threonine-protein kinase LATS2
Enzyme Classification 2.7.11.1
UniProt Q9NRM7

Also Known as LATS2_HUMAN, LATS2, KPM

Negative regulator of YAP1 in the Hippo signaling pathway that 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. Acts as a tumor suppressor which plays a critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability. Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity. Negative regulator of the androgen receptor. Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities. This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ. Interacts with and is phosphorylated by AURKA. Binds to AR. Interacts with AJUBA during mitosis and this complex regulates organization of the spindle apparatus through recruitment of gamma-tubulin to the centrosome. Interacts (via PPxY motif) with YAP1 (via WW domains). Interacts with MOB1A and MOB1B. Interacts with LIMD1, WTIP and AJUBA. Interacts with SNAI1.

4ZRI
20 RESIDUE FRAGMENT OF
SERINE/THREONINE-PROTEIN KINASE LATS2
IN THE STRUCTURE OF
CRYSTAL STRUCTURE OF MERLIN-FERM AND LATS2
RCSB/PDB
Inspect Structure
See all 3D Structures for LATS2

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
1088ENSG00000150457ENST00000542899, ENST00000382592ENSP00000441817, ENSP00000372035Q9NRM7-1

Sub-cellular localization


UniProt: LATS2 is active in the following subcellular-locations: centrosome, cytoplasm, cytoskeleton, microtubule organizing center, nucleus, spindle pole.
GO terms: LATS2 is active in the following subcellular-locations: cytosol, microtubule organizing center, nucleus, spindle pole.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project LATS2 has gain in 3 cell-lines, loss in 5 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: ACHN, SF_268, SF_539

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H1568, CaR-1, MKN-74

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, NHLF

(see details)

RNA Interference


LATS2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: G292, H2342. (see details)

3D Structures


For LATS2 there are:
1 structures (2 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


LATS2 has been screened with 100 compounds (138 bioactivities), 6 compounds have bioactivities that show binding affinity of <= 500nM (11 bioactivities). (see details)