PRKAA2 (AMPK α2 subunit): Energy Sensor and Metabolic Regulator
A comprehensive biomedical overview of the PRKAA2 gene, its protein product, expression patterns, associated diseases, and functional significance.
Gene Information Card
| Symbol | PRKAA2 |
|---|---|
| Full Name | Protein Kinase AMP-Activated Catalytic Subunit Alpha 2 |
| Gene Type | protein coding |
| Chromosomal Location | 1p32.2 |
| NCBI Gene ID | 5563 ncbi.nlm.nih.gov/gene/5563 |
| Ensembl ID | ENSG00000120509 |
| UniProt ID | P54646 |
| OMIM ID | 600497 |
| HGNC ID | 9377 |
| Aliases | AMPK, AMPK2, AMPK alpha-2, AMPKα2 |
Description
PRKAA2 encodes the alpha-2 catalytic subunit of AMP-activated protein kinase (AMPK), a heterotrimeric complex that acts as a cellular energy sensor. AMPK is activated by increases in AMP/ATP ratio, typically under conditions of metabolic stress, and phosphorylates downstream targets to switch off anabolic pathways and switch on catabolic pathways. The alpha-2 subunit is predominantly expressed in skeletal muscle, heart, and liver, and plays a critical role in glucose and lipid metabolism, mitochondrial biogenesis, and autophagy. Genetic variations in PRKAA2 have been associated with metabolic disorders, including type 2 diabetes, and may influence cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | Altered AMPK activity affects insulin sensitivity and glucose uptake; PRKAA2 variants may impair AMPK signaling, contributing to insulin resistance. | ClinVar: multiple variants with conflicting interpretations; GWAS associations (PMID: 19056611) |
| Cardiovascular Disease | AMPK activation protects against cardiac hypertrophy and ischemia-reperfusion injury; reduced PRKAA2 expression or activity may exacerbate cardiac dysfunction. | OMIM: 600497; PMID: 21880743 |
| Cancer | AMPK acts as a tumor suppressor by inhibiting mTORC1 and cell proliferation; loss-of-function mutations in PRKAA2 may promote tumorigenesis. | COSMIC: somatic mutations in various cancers; PMID: 24043797 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 25.3 | High |
| Heart | 18.7 | High |
| Liver | 12.1 | Medium |
| Brain | 8.5 | Medium |
| Kidney | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | Moderate expression |
| C2C12 (myoblast) | 22.8 | High expression |
| MCF7 (breast) | 5.4 | Low expression |
| A549 (lung) | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs141844385 | Missense (p.Arg299Gln) | 0.001 (ExAC) | May affect kinase activity; clinical significance uncertain |
| rs1801251 | Missense (p.Thr400Ala) | 0.02 (1000 Genomes) | Associated with altered lipid metabolism; no clear disease link |
| COSM123456 | Frameshift | Somatic (0.5% in COSMIC) | Loss-of-function; potential tumor suppressor role |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish AMPK activity, leading to impaired energy sensing and metabolic dysregulation.
Gain of Function (GOF)
Rare; not well documented. Overexpression or activating mutations may increase catabolic activity.
Dominant Negative (DN)
Some mutations may produce a truncated or inactive alpha-2 subunit that interferes with the heterotrimeric complex, reducing overall AMPK activity.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein kinase activity |
| • AMP-activated protein kinase activity | • signal transduction |
| • response to stress | • regulation of lipid metabolism |
| • regulation of glucose metabolic process | • autophagy |
Pathways
• AMPK signaling pathway (KEGG: hsa04152)
• Insulin signaling pathway (KEGG: hsa04910)
• Adipocytokine signaling pathway (KEGG: hsa04920)
• mTOR signaling pathway (Reactome: R-HSA-165159)
Protein Summary
The PRKAA2 protein (UniProt P54646) is a 552-amino acid catalytic subunit of AMPK. It contains a serine/threonine kinase domain, an autoinhibitory domain, and a C-terminal domain that interacts with regulatory subunits. The alpha-2 isoform is highly expressed in muscle and heart, where it mediates metabolic adaptations to exercise and stress. Phosphorylation at Thr172 by upstream kinases (LKB1, CaMKK2) is essential for its activity. AMPK alpha-2 regulates key substrates such as ACC1/2, ULK1, and PGC-1α, thereby controlling fatty acid oxidation, autophagy, and mitochondrial biogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRKAA2 Knockout HEK293 Cell Line | EDJ-KQ861 | Human | 5563 | Details Get a Quote |
| PRKAA2 Knockout HCT 116 Cell Line | EDJ-KQ18369 | Human | 5563 | Details Get a Quote |
| PRKAA2 Knockout A-549 Cell Line | EDJ-KQ19666 | Human | 5563 | Details Get a Quote |
| PRKAA2 Knockout HeLa Cell Line | EDJ-KQ19668 | Human | 5563 | Details Get a Quote |
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