PRKAA1
Protein Kinase AMP-Activated Catalytic Subunit Alpha 1
Gene Information Card
| Symbol | PRKAA1 |
|---|---|
| Full Name | Protein Kinase AMP-Activated Catalytic Subunit Alpha 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 5p13.1 |
| NCBI Gene ID | 5562 ncbi.nlm.nih.gov/gene/5562 |
| Ensembl ID | ENSG00000132356 |
| UniProt ID | Q13131 |
| OMIM ID | 602739 |
| HGNC ID | 9376 |
| Aliases | AMPK alpha 1, AMPKa1, C10orf12, MGC33776 |
Description
PRKAA1 encodes the catalytic alpha 1 subunit of AMP-activated protein kinase (AMPK), a heterotrimeric complex that acts as a cellular energy sensor. AMPK is activated under low-energy conditions (high AMP/ATP ratio) and phosphorylates downstream targets to promote catabolic processes (e.g., glucose uptake, fatty acid oxidation) and inhibit anabolic pathways (e.g., protein synthesis, gluconeogenesis). PRKAA1 is ubiquitously expressed and plays critical roles in metabolism, autophagy, cell growth, and stress responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Dysregulation of AMPK signaling alters cellular metabolism and promotes tumor growth; PRKAA1 mutations or altered expression linked to breast, lung, and colorectal cancers. | COSMIC; ClinVar |
| Type 2 Diabetes | Reduced AMPK activity impairs insulin sensitivity and glucose homeostasis; PRKAA1 variants associated with metabolic syndrome. | NCBI Gene; OMIM |
| Cardiac Hypertrophy | AMPK inactivation contributes to pathological cardiac remodeling; PRKAA1 deficiency exacerbates hypertrophy in models. | UniProt; PubMed |
| Neurodegenerative Diseases | AMPK dysregulation implicated in Alzheimer's and Parkinson's; PRKAA1 modulates tau phosphorylation and autophagy. | NCBI Gene; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Skeletal Muscle | 18.3 | High |
| Heart | 15.7 | High |
| Brain | 10.2 | Medium |
| Adipose Tissue | 8.9 | Medium |
| Pancreas | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.1 | Cervical cancer cell line |
| HepG2 | 16.8 | Hepatocellular carcinoma |
| A549 | 11.3 | Lung adenocarcinoma |
| MCF7 | 9.7 | Breast cancer |
| SH-SY5Y | 7.5 | Neuroblastoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.491C>T (p.Thr164Ile) | Missense | <0.1% | Reduced kinase activity; associated with metabolic syndrome |
| c.1000G>A (p.Glu334Lys) | Missense | <0.05% | Impaired AMP binding; loss of function |
| c.1345C>T (p.Arg449Trp) | Missense | <0.01% | Decreased catalytic activity; reported in cancer |
| c.1726_1727del (p.Leu576fs) | Frameshift | Rare | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., Thr164Ile, Glu334Lys) reduce kinase activity; frameshift deletions cause truncation and loss of catalytic function.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in PRKAA1.
Dominant Negative (DN)
Some missense mutations (e.g., Asp157Ala) can act as dominant-negative by forming inactive heterotrimers, but not commonly observed in natural variants.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 - protein kinase activity | • GO:0005524 - ATP binding |
| • GO:0004679 - AMP-activated protein kinase activity | • GO:0006468 - protein phosphorylation |
| • GO:0016310 - phosphorylation | • GO:0042593 - glucose homeostasis |
| • GO:0006914 - autophagy | • GO:0008286 - insulin receptor signaling pathway |
| • GO:0005737 - cytoplasm | • GO:0005634 - nucleus |
Pathways
• AMPK signaling pathway (KEGG: hsa04152)
• Insulin signaling pathway (KEGG: hsa04910)
• mTOR signaling pathway (KEGG: hsa04150)
• Autophagy (KEGG: hsa04140)
• Adipocytokine signaling pathway (KEGG: hsa04920)
Protein Summary
PRKAA1 encodes the catalytic alpha 1 subunit of AMPK, a heterotrimeric serine/threonine kinase complex. The protein contains an N-terminal kinase domain, an autoinhibitory domain, and a C-terminal domain that mediates interaction with regulatory beta and gamma subunits. AMPK is activated by phosphorylation at Thr172 by upstream kinases (LKB1, CaMKK2) in response to elevated AMP/ATP ratio. PRKAA1 is ubiquitously expressed and regulates energy homeostasis, cell growth, autophagy, and stress resistance. Dysregulation of PRKAA1 is implicated in metabolic disorders, cancer, and cardiovascular diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRKAA1 Knockout HEK293 Cell Line | EDJ-KQ860 | Human | 5562 | Details Get a Quote |
| PRKAA1 Knockout HeLa Cell Line | EDJ-KQ18312 | Human | 5562 | Details Get a Quote |
| PRKAA1 Knockout A-549 Cell Line | EDJ-KQ19664 | Human | 5562 | Details Get a Quote |
| PRKAA1 Knockout HCT 116 Cell Line | EDJ-KQ19665 | Human | 5562 | Details Get a Quote |
| PRKAA1 Knockout HAP1 Cell Line | EDC07917 | Human | 5562 | Details Get a Quote |
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