Tchem LATS1 Serine/threonine-protein kinase LATS1

Protein Summary

Description

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). The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. The N-terminal region of the protein binds CDC2 to form a complex showing reduced H1 histone kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a tumor suppressor. This is supported by studies in knockout mice showing development of soft-tissue sarcomas, ovarian stromal cell tumors and a high sensitivity to carcinogenic treatments. [provided by RefSeq, Apr 2017]

Uniprot Accession IDs

• O95835
• Q6PKD0

Gene Name

• LATS1

Ensembl ID

• ENST00000253339
• ENSP00000253339
• ENSG00000131023
• ENST00000392273
• ENSP00000444678
• ENST00000543571
• ENSP00000437550

Symbol

• WARTS
• wts
• WARTS

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.99
molecular function	0.97
biological process	0.91
kinase	0.8
histone modification site profile	0.71

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Serine/threonine-protein Kinase Lats1

Protein / Transfer/carrier Protein / Serine/threonine-protein Kinase Lats1

Protein / Calcium-binding Protein / Intracellular Calcium-sensing Protein / Calmodulin / Serine/threonine-protein Kinase Lats1

Protein / Calcium-binding Protein / Annexin / Serine/threonine-protein Kinase Lats1

DTO Classes

Protein / Kinase / Protein Kinase / Agc Group / Ndr Family / Serine/threonine-protein Kinase Lats1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 311   (req: < 5)

Gene RIFs: 117   (req: <= 3)

Antibodies: 348   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 311   (req: >= 5)

Gene RIFs: 117   (req: > 3)

Antibodies: 348   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 29

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 184

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0