SIK2 (Salt Inducible Kinase 2)
A key regulator of cellular metabolism, cell cycle, and cancer signaling pathways
Gene Information Card
| Symbol | SIK2 |
|---|---|
| Full Name | Salt Inducible Kinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q23.1 |
| NCBI Gene ID | 23235 ncbi.nlm.nih.gov/gene/23235 |
| Ensembl ID | ENSG00000174697 |
| UniProt ID | Q9H0K1 |
| OMIM ID | 608622 |
| HGNC ID | 20219 |
| Aliases | SNF1LK2, QIK, KIAA0781 |
Description
SIK2 (Salt Inducible Kinase 2) is a serine/threonine protein kinase belonging to the AMPK-related kinase family. It plays critical roles in cellular energy homeostasis, cell cycle regulation, and signal transduction. SIK2 is involved in the regulation of gluconeogenesis, lipolysis, and insulin signaling. It also functions as a tumor suppressor or oncogene depending on cellular context, with implications in ovarian, breast, and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ovarian cancer | SIK2 overexpression promotes cell proliferation and migration via PI3K/AKT and mTOR pathways | PMID: 25605247 |
| Breast cancer | SIK2 loss-of-function mutations are associated with poor prognosis and altered metabolism | PMID: 28394336 |
| Type 2 diabetes | SIK2 regulates hepatic gluconeogenesis and insulin sensitivity | PMID: 20074528 |
| Adiposity and obesity | SIK2 modulates adipocyte differentiation and lipid metabolism | PMID: 21880732 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Liver | 8.3 | Low |
| Brain | 6.1 | Low |
| Ovary | 15.2 | Medium |
| Breast | 9.7 | Low |
| Testis | 18.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical cancer cell line |
| MCF7 | 11.5 | Breast cancer cell line |
| OVCAR3 | 22.1 | Ovarian cancer cell line |
| HepG2 | 7.8 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | <0.1% | Loss of kinase activity; associated with breast cancer |
| c.1456G>A (p.Glu486Lys) | Missense | <0.1% | Unknown functional effect; reported in COSMIC |
| c.1789_1790insA (p.Thr597Asnfs*12) | Frameshift | <0.1% | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that impair kinase activity or protein stability, e.g., p.Arg375Trp.
Gain of Function (GOF)
Not well characterized; overexpression in ovarian cancer may act as a gain-of-function mechanism.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 (protein kinase activity) | • GO:0005524 (ATP binding) |
| • GO:0006468 (protein phosphorylation) | • GO:0006094 (gluconeogenesis) |
| • GO:0042593 (glucose homeostasis) | • GO:0007049 (cell cycle) |
| • GO:0018105 (peptidyl-serine phosphorylation) |
Pathways
• AMPK signaling pathway (KEGG: hsa04152)
• Insulin signaling pathway (KEGG: hsa04910)
• mTOR signaling pathway (KEGG: hsa04150)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
Protein Summary
SIK2 is a 926-amino acid serine/threonine kinase with an N-terminal kinase domain, a ubiquitin-associated (UBA) domain, and a C-terminal regulatory region. It phosphorylates targets such as CRTC2 and HDACs to regulate gene expression. SIK2 activity is modulated by phosphorylation by LKB1 and by autophosphorylation. It localizes to the cytoplasm and nucleus, and its expression is regulated by cellular energy status.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIK2 Knockout HEK293 Cell Line | EDJ-KQ2070 | Human | 23235 | Details Get a Quote |
| SIK2 Knockout A-549 Cell Line | EDJ-KQ22142 | Human | 23235 | Details Get a Quote |
| SIK2 Knockout HCT 116 Cell Line | EDJ-KQ22143 | Human | 23235 | Details Get a Quote |
| SIK2 Knockout HeLa Cell Line | EDJ-KQ22144 | Human | 23235 | Details Get a Quote |
| SIK2 Knockout HAP1 Cell Line | EDC07866 | Human | 23235 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
