AKT2: A Key Serine/Threonine Kinase in Insulin Signaling and Cancer
Comprehensive genomic and functional overview of the AKT2 gene, its role in metabolic regulation, oncogenic signaling, and associated diseases.
Gene Information Card
| Symbol | AKT2 |
|---|---|
| Full Name | AKT serine/threonine kinase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 208 ncbi.nlm.nih.gov/gene/208 |
| Ensembl ID | ENSG00000105221 |
| UniProt ID | P31751 |
| OMIM ID | 164731 |
| HGNC ID | 392 |
| Aliases | PKB beta, PKBB, PRKBB, RAC-beta |
Description
AKT2 (AKT serine/threonine kinase 2) encodes a member of the AKT subfamily of serine/threonine kinases, also known as protein kinase B (PKB) beta. This kinase is a critical downstream effector of phosphatidylinositol 3-kinase (PI3K) and mediates signals for cell survival, growth, proliferation, and metabolism. AKT2 is particularly important in insulin signaling and glucose homeostasis. Alterations in AKT2, including gain-of-function mutations and amplifications, are associated with various cancers, while loss-of-function mutations can lead to hypoinsulinemic hypoglycemia with hemihypertrophy.
Disease Associations
| Disease Name | Disease Description |
|---|---|
| Prostate cancer | Gain-of-function mutations (e.g., E17K) lead to constitutive activation of AKT2, promoting cell survival and proliferation via PI3K/AKT/mTOR pathway activation. |
| Breast cancer | Amplification and overexpression of AKT2 enhance PI3K signaling, contributing to tumor progression and resistance to therapy. |
| Ovarian cancer | AKT2 amplification and activating mutations drive oncogenic signaling, associated with poor prognosis. |
| Hypoinsulinemic hypoglycemia with hemihypertrophy | Loss-of-function mutations in AKT2 impair insulin signaling, leading to defective glucose uptake and hypoglycemia. |
| Non-small cell lung cancer | AKT2 overexpression and activation correlate with increased metastatic potential and reduced survival. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Skeletal muscle | 10.8 | Medium |
| Liver | 8.2 | Medium |
| Heart | 7.1 | Low |
| Brain | 6.5 | Low |
| Kidney | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.3 | High expression; associated with PI3K pathway activation |
| PC3 (prostate cancer) | 14.1 | High expression; linked to aggressive phenotype |
| A549 (lung cancer) | 11.7 | Moderate expression |
| HepG2 (liver cancer) | 9.8 | Moderate expression |
| SKOV3 (ovarian cancer) | 13.5 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Mutation site | Type | Frequency | Functional Description |
|---|---|---|---|
| E17K | Missense | 0.5% in breast cancer; 1.2% in prostate cancer | Gain-of-function; constitutive membrane localization and activation |
| R67H | Missense | <0.1% | Likely loss-of-function; associated with hypoglycemia |
| D32Y | Missense | <0.1% | Unknown; reported in COSMIC |
| Amplification | Copy number gain | 5-10% in ovarian and breast cancers | Increased AKT2 expression and pathway activation |
Mutation functional classification
Loss of Function (LOF)
R67H and other rare missense variants impair kinase activity, reducing insulin-stimulated glucose uptake and leading to hypoglycemia.
Gain of Function (GOF)
E17K is a well-characterized activating mutation that enhances membrane recruitment and constitutive signaling, promoting oncogenesis.
Dominant Negative (DN)
No dominant-negative mutations are currently documented in ClinVar or COSMIC for AKT2.
View complete mutation data：ClinVar: https://www.clinvar.com/gene/208 COSMIC: https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=AKT2
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • phosphatidylinositol 3-kinase binding | • protein kinase B signaling |
| • positive regulation of cell proliferation | • negative regulation of apoptotic process |
| • insulin receptor signaling pathway | • glucose homeostasis |
| • cellular response to growth factor stimulus |
Pathways
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Insulin signaling pathway (KEGG: hsa04910)
• mTOR signaling pathway (KEGG: hsa04150)
• FoxO signaling pathway (KEGG: hsa04068)
• Apoptosis (KEGG: hsa04210)
Protein Summary
AKT2 is a 481-amino acid serine/threonine kinase with an N-terminal pleckstrin homology (PH) domain, a central kinase domain, and a C-terminal regulatory tail. Upon PI3K activation, AKT2 is recruited to the plasma membrane via its PH domain and phosphorylated at Thr309 and Ser474 by PDK1 and mTORC2, respectively. Activated AKT2 phosphorylates numerous substrates involved in cell survival (e.g., BAD, FOXO), metabolism (e.g., GSK3, AS160), and protein synthesis (e.g., TSC2, PRAS40). In cancer, hyperactivation of AKT2 promotes resistance to apoptosis, increased glycolysis, and metastasis. In metabolic disorders, loss of AKT2 function disrupts insulin signaling, leading to impaired glucose uptake.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKT2 Knockout HEK293 Cell Line | EDJ-KQ448 | Human | 208 | Details Get a Quote |
| AKT2 Knockout HeLa Cell Line | EDJ-KQ18342 | Human | 208 | Details Get a Quote |
| AKT2 Knockout A-549 Cell Line | EDC90043 | Human | 208 | Details Get a Quote |
| AKT2 Knockout HCT 116 Cell Line | EDJ-KQ18751 | Human | 208 | Details Get a Quote |
| AKT2 (p.R251W) Point Mutation in HAP1 Cell Line | EDC03397 | Human | 208 | Details Get a Quote |
| AKT1 and AKT2 Knockout A-549 Cell Line | EDC90155 | Human | 207 and 208 | Details Get a Quote |
| AKT2 and AKT3 Knockout A-549 Cell Line | EDC90416 | Human | 208 and 10000 | Details Get a Quote |
Displaying Records 1 To 7 Of 7 Records
