LATS2
LATS2 (Serine/threonine-protein kinase LATS2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Mesothelioma, Skin cancer, Colorectal cancer and 5 more.
Overview
Negative regulator of YAP1 in the Hippo signalling pathway that plays a pivotal role in organ size control and tumour 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.
Open Targets scores its association with cancer at 0.69 (direct and indirect evidence; datatypes literature 0.99, genetic association 0.00, somatic mutation 0.83). IntOGen calls it a driver in 5 cohorts (1 activating, 4 loss-of-function), covering Lung Squamous Cell Carcinoma, Pilocytic Astrocytoma, Pleural Mesothelioma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · LATS2 (Serine/threonine-protein kinase LATS2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Mesothelioma, Skin cancer, Colorectal cancer and 5 more.
- 1 · What it is
LATS2 (Serine/threonine-protein kinase LATS2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Mesothelioma, Skin cancer, Colorectal cancer and 5 more.
- 2 · What goes wrong in cancer
Negative regulator of YAP1 in the Hippo signalling pathway that plays a pivotal role in organ size control and tumour suppression by restricting proliferation and promoting apoptosis.
- 3 · How drugs use it
No product in this corpus aims at LATS2 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:6515 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9NRM7 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000150457 (association with cancer (MONDO_0004992) 0.69; per-cancer scores at or above 0.5: colorectal cancer 0.55, melanoma 0.50, skin cancer 0.55, breast cancer 0.54 (GraphQL API, CC0)); IntOGen LATS2 (driver in 5 cohorts (Act 1, LoF 4); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Negative regulator of YAP1 in the Hippo signalling pathway that plays a pivotal role in organ size control and tumour 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. Also phosphorylates YAP1 in response to cell contact inhibition-driven WWP1 ubiquitination of AMOTL2, which results in LATS2 activation. Acts as a tumour 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. Location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm; Cytoplasm, cytoskeleton, spindle pole; Nucleus (UniProt). Locus 13q12.11 (HGNC).
- Mesothelioma: IntOGen driver in 3 cohorts (PLMESO)
- Skin cancer: Open Targets association 0.55 with skin cancer (MONDO_0002898)
- Colorectal cancer: Open Targets association 0.55 with colorectal cancer (MONDO_0005575)
- Breast cancer: Open Targets association 0.54 with breast cancer (MONDO_0007254)
- Pleural mesothelioma: IntOGen driver in 3 cohorts (PLMESO)
- Non-small-cell lung cancer: IntOGen driver in 1 cohort (LUSC)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 4 cohorts. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"LATS2" OR ABSTRACT:"LATS2" OR TITLE:"large tumor suppressor kinase 2" OR ABSTRACT:"large tumor suppressor kinase 2" OR TITLE:"Serine/threonine-protein kinase LATS2" OR ABSTRACT:"Serine/threonine-protein kinase LATS2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about LATS2, not a curated reading list.
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