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

LATS1 (O95835) - Overview - Molecular Target Synopsis

Protein


LATS1, Serine/threonine-protein kinase LATS1
Enzyme Classification 2.7.11.1
UniProt O95835

Also Known as LATS1_HUMAN, LATS1, WARTS

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 LATS1 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 maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDK1 kinase activity. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. May also play a role in endocrine function. Plays a role in mammary gland epithelial cells differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1 (PubMed:28068668). Complexes with CDK1 in early mitosis. LATS1-associated CDK1 has no mitotic cyclin partner and no apparent kinase activity. Binds phosphorylated ZYX, locating this protein to the mitotic spindle and suggesting a role for actin regulatory proteins during mitosis. Binds to and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis. Interacts (via PPxY motif 2) with YAP1 (via WW domains). Interacts with MOB1A and MOB1B. Interacts with LIMD1, WTIP and AJUBA. Interacts with ESR1, DCAF1 and DCAF13; probably recruits DCAF1 and DCAF13 to ESR1 to promote ESR1 ubiquitination and ubiquitin-mediated proteasomal degradation (PubMed:28068668). Interacts with STK3/MST2; this interaction is inhibited in the presence of DLG5 (PubMed:28087714). Interacts with SCRIB in the presence of DLG5 (PubMed:28169360).

5B5W
CRYSTAL STRUCTURE OF MOB1-LATS1 NTR DOMAIN COMPLEX
RCSB/PDB
Inspect Structure
See all 3D Structures for LATS1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: LATS1 is active in the following subcellular-locations: centrosome, cytoplasm, cytoskeleton, microtubule organizing center.
GO terms: LATS1 is active in the following subcellular-locations: cytosol, microtubule organizing center, spindle pole.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project LATS1 has gain in 0 cell-lines, loss in 5 cell-lines and no signal in 1000 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, TK_10, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H209, NCI-H1882, HEL

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: HSMM, NHLF, BJ

(see details)

RNA Interference


LATS1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HCC38, SKGT4. (see details)

3D Structures


For LATS1 there are:
3 structures (6 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


LATS1 has been screened with 99 compounds (137 bioactivities), 4 compounds have bioactivities that show binding affinity of <= 500nM (7 bioactivities). (see details)