NUAK2: A Key Regulator of Cell Proliferation and Survival
Comprehensive genomic and functional analysis of NUAK2 (SNARK) in health and disease
Gene Information Card
| Symbol | NUAK2 |
|---|---|
| Full Name | NUAK family kinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 81788 ncbi.nlm.nih.gov/gene/81788 |
| Ensembl ID | ENSG00000117676 |
| UniProt ID | Q9H093 |
| OMIM ID | 608131 |
| HGNC ID | 29558 |
| Aliases | SNARK, FLJ90358 |
Description
NUAK2 (NUAK family kinase 2), also known as SNARK, is a serine/threonine protein kinase belonging to the AMPK-related kinase family. It plays a critical role in regulating cell proliferation, survival, and metabolism. NUAK2 is involved in cellular stress responses and has been implicated in cancer progression, particularly through its effects on the Hippo signaling pathway and MYC stability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | NUAK2 overexpression promotes cell proliferation and tumor growth via MYC stabilization and YAP activation. | COSMIC; PMID: 29281825 |
| Breast cancer | NUAK2 amplification and overexpression correlate with poor prognosis and resistance to therapy. | COSMIC; PMID: 25605248 |
| Colorectal cancer | NUAK2 upregulation enhances cell migration and invasion through actin cytoskeleton remodeling. | COSMIC; PMID: 27626308 |
| Pancreatic cancer | NUAK2 silencing reduces tumor growth and metastasis in preclinical models. | COSMIC; PMID: 30356099 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Breast | 8.7 | Medium |
| Colon | 10.1 | Medium |
| Pancreas | 6.5 | Low |
| Lung | 9.4 | Medium |
| Kidney | 7.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.6 | Hepatocellular carcinoma cell line |
| MCF7 | 11.2 | Breast cancer cell line |
| HCT116 | 13.8 | Colorectal carcinoma cell line |
| PANC-1 | 9.5 | Pancreatic cancer cell line |
| A549 | 10.3 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.1% | Unknown functional impact; reported in COSMIC |
| c.1342G>A (p.Glu448Lys) | Missense | <0.1% | Unknown functional impact; reported in COSMIC |
| c.1660C>T (p.Arg554*) | Nonsense | <0.1% | Predicted loss of function; truncating mutation |
| c.1885_1886insA (p.Leu629fs) | Frameshift | <0.1% | Predicted loss of function; frameshift insertion |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg554*, p.Leu629fs) are predicted to result in truncated or non-functional NUAK2 protein, leading to loss of kinase activity.
Gain of Function (GOF)
Amplification and overexpression of NUAK2 in cancers suggest a gain-of-function role, though specific activating point mutations are not well characterized.
Dominant Negative (DN)
No dominant-negative mutations have been reported for NUAK2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hippo signaling pathway (Reactome: R-HSA-2028269)
• AMPK signaling (KEGG: hsa04152)
• Signaling by Receptor Tyrosine Kinases (Reactome: R-HSA-9006934)
Protein Summary
NUAK2 is a 628-amino acid serine/threonine kinase with an N-terminal kinase domain. It is activated by phosphorylation and functions downstream of LKB1 and AMPK. NUAK2 regulates cell polarity, migration, and survival by phosphorylating substrates such as MYPT1 and regulating YAP/TAZ activity. Its overexpression in multiple cancers highlights its role as a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NUAK2 Knockout HEK293 Cell Line | EDJ-KQ3323 | Human | 81788 | Details Get a Quote |
| NUAK2 Knockout A-549 Cell Line | EDJ-KQ24931 | Human | 81788 | Details Get a Quote |
| NUAK2 Knockout HCT 116 Cell Line | EDJ-KQ24932 | Human | 81788 | Details Get a Quote |
| NUAK2 Knockout HeLa Cell Line | EDJ-KQ24933 | Human | 81788 | Details Get a Quote |
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