LATS1: A Core Hippo Pathway Kinase and Tumor Suppressor
Comprehensive genomic and functional overview of LATS1, a key regulator of organ size control and cancer suppression.
Gene Information Card
| Symbol | LATS1 |
|---|---|
| Full Name | Large tumor suppressor kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q25.1 |
| NCBI Gene ID | 9113 ncbi.nlm.nih.gov/gene/9113 |
| Ensembl ID | ENSG00000115808 |
| UniProt ID | O95835 |
| OMIM ID | 603473 |
| HGNC ID | 6514 |
| Aliases | wts, WARTS, LATS, serine/threonine-protein kinase LATS1 |
Description
LATS1 (large tumor suppressor kinase 1) encodes a serine/threonine protein kinase that is a core component of the Hippo signaling pathway. It functions as a tumor suppressor by phosphorylating and inhibiting the transcriptional coactivators YAP1 and WWTR1 (TAZ), thereby regulating organ size, cell proliferation, and apoptosis. LATS1 is also involved in cell cycle regulation, mitotic progression, and cytoskeletal dynamics. Loss or mutation of LATS1 is associated with various cancers, including breast, ovarian, and soft tissue sarcomas.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | LATS1 loss leads to YAP1 nuclear translocation and increased proliferation | PMID: 21145449; COSMIC |
| Ovarian cancer | LATS1 downregulation correlates with poor prognosis and chemoresistance | PMID: 22198284; ClinVar |
| Soft tissue sarcoma | LATS1 mutations and deletions are recurrent in malignant peripheral nerve sheath tumors | PMID: 24755471; COSMIC |
| Prostate cancer | LATS1 inactivation promotes metastasis via YAP1 activation | PMID: 25977310; NCBI Gene |
| Liver cancer | LATS1 deficiency accelerates hepatocellular carcinoma in mouse models | PMID: 20075857; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 5.2 | Low |
| Breast | 8.1 | Medium |
| Colon | 6.3 | Low |
| Kidney | 12.4 | Medium |
| Liver | 4.7 | Low |
| Lung | 9.8 | Medium |
| Ovary | 11.5 | Medium |
| Prostate | 7.9 | Medium |
| Skin | 6.1 | Low |
| Testis | 15.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 10.2 | Basal expression; reduced in aggressive subtypes |
| HeLa (cervical cancer) | 8.7 | Moderate expression |
| A549 (lung cancer) | 7.5 | Reduced compared to normal lung |
| HepG2 (liver cancer) | 5.1 | Low expression |
| SK-OV-3 (ovarian cancer) | 6.8 | Variable; loss correlates with resistance |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <1% | Truncation; loss of kinase domain |
| c.789_790del (p.Glu264fs) | Frameshift | <1% | Loss of function |
| c.1675A>G (p.Thr559Ala) | Missense | <0.5% | Reduced kinase activity |
| c.2101C>T (p.Arg701Trp) | Missense | <0.5% | Impaired YAP1 binding |
| c.2542G>A (p.Glu848Lys) | Missense | <0.5% | Unknown significance |
Mutation functional classification
Loss of Function (LOF)
Most LATS1 mutations in cancer are loss-of-function, including nonsense, frameshift, and missense variants that impair kinase activity or YAP1 binding.
Gain of Function (GOF)
No gain-of-function mutations have been reported for LATS1.
Dominant Negative (DN)
Dominant-negative effects have not been described for LATS1; loss of heterozygosity is common.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 - protein kinase activity | • GO:0004674 - serine/threonine kinase activity |
| • GO:0005515 - protein binding | • GO:0005634 - nucleus |
| • GO:0005737 - cytoplasm | • GO:0005813 - centrosome |
| • GO:0007049 - cell cycle | • GO:0008285 - negative regulation of cell proliferation |
| • GO:0016310 - phosphorylation | • GO:0035329 - hippo signaling |
| • GO:0043066 - negative regulation of apoptotic process | • GO:2000270 - negative regulation of fibroblast growth factor receptor signaling pathway |
Pathways
• Hippo signaling pathway (KEGG: hsa04390)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
• Cell cycle (KEGG: hsa04110)
• Signaling by WNT (Reactome: R-HSA-195721)
• YAP1/TAZ coactivators regulation (Reactome: R-HSA-8939211)
Protein Summary
LATS1 is a 1130-amino-acid serine/threonine kinase (UniProt O95835) containing an N-terminal UBA domain, a central kinase domain, and a C-terminal regulatory region. It is activated by MST1/2-mediated phosphorylation and forms a complex with MOB1. Active LATS1 phosphorylates YAP1 at Ser127 and TAZ at Ser89, promoting their cytoplasmic retention and degradation. LATS1 also localizes to centrosomes and mitotic spindles, where it regulates mitotic progression. Loss of LATS1 leads to uncontrolled YAP1/TAZ activity, driving cell proliferation and tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LATS1 Knockout HEK293 Cell Line | EDJ-KQ1375 | Human | 9113 | Details Get a Quote |
| LATS1 Knockout A-549 Cell Line | EDJ-KQ19530 | Human | 9113 | Details Get a Quote |
| LATS1 Knockout HCT 116 Cell Line | EDJ-KQ20875 | Human | 9113 | Details Get a Quote |
| LATS1 Knockout HeLa Cell Line | EDJ-KQ20876 | Human | 9113 | Details Get a Quote |
| LATS1 Knockout HAP1 Cell Line | EDC08068 | Human | 9113 | Details Get a Quote |
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