The Function of PRKAA1
Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.
Protein names
Recommended name:
5'-AMP-activated protein kinase catalytic subunit alpha-1Alternative name(s):
AMPK subunit alpha-1Acetyl-CoA carboxylase kinase
ACACA kinase
Hydroxymethylglutaryl-CoA reductase kinase
HMGCR kinase
Tau-protein kinase PRKAA1
- RS10074991 (PRKAA1) ??
- RS13361707 (PRKAA1) ??
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Top Gene-Substance Interactions
PRKAA1 Interacts with These Diseases
| Disease | Score |
Substances That Increase PRKAA1
| Substances | Interaction | Organism | Category |
Substances That Decrease PRKAA1
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Gene Pathways:
Enzyme Regulation:
Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (PubMed:11602624). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol.
Molecular Function:
- Chromatin Binding
- Amp-Activated Protein Kinase Activity
- Camp-Dependent Protein Kinase Activity
- Atp Binding
- Histone Serine Kinase Activity
- Metal Ion Binding
- [Hydroxymethylglutaryl-Coa Reductase (Nadph)] Kinase Activity
- Tau-Protein Kinase Activity
- [Acetyl-Coa Carboxylase] Kinase Activity
Biological Processes:
- Activation Of Mapk Activity
- Response To Hypoxia
- Glucose Metabolic Process
- Transcription, Dna-Templated
- Regulation Of Transcription, Dna-Templated
- Protein Phosphorylation
- Fatty Acid Biosynthetic Process
- Cholesterol Biosynthetic Process
- Cell Cycle Arrest
- Signal Transduction
- Positive Regulation Of Cell Proliferation
- Lipid Biosynthetic Process
- Response To Uv
- Cold Acclimation
- Response To Gamma Radiation
- Positive Regulation Of Autophagy
- Positive Regulation Of Gene Expression
- Wnt Signaling Pathway
- Macroautophagy
- Fatty Acid Oxidation
- Response To Caffeine
- Cellular Response To Nutrient Levels
- Negative Regulation Of Tor Signaling
- Regulation Of Peptidyl-Serine Phosphorylation
- Intracellular Signal Transduction
- Cellular Response To Glucose Starvation
- Glucose Homeostasis
- Regulation Of Circadian Rhythm
- Negative Regulation Of Apoptotic Process
- Positive Regulation Of Cholesterol Biosynthetic Process
- Positive Regulation Of Glycolytic Process
- Negative Regulation Of Glucosylceramide Biosynthetic Process
- Rhythmic Process
- Positive Regulation Of Skeletal Muscle Tissue Development
- Negative Regulation Of Lipid Catabolic Process
- Protein Heterooligomerization
- Fatty Acid Homeostasis
- Regulation Of Vesicle-Mediated Transport
- Camkk-Ampk Signaling Cascade
- Cellular Response To Hydrogen Peroxide
- Cellular Response To Ethanol
- Cellular Response To Prostaglandin E Stimulus
- Cellular Response To Organonitrogen Compound
- Cellular Response To Hypoxia
- Response To Camptothecin
- Regulation Of Signal Transduction By P53 Class Mediator
- Regulation Of Energy Homeostasis
- Negative Regulation Of Glucose Import In Response To Insulin Stimulus
Drug Bank:
- Acetylsalicylic Acid
- Adenosine Triphosphate
- Phenformin
- Adenosine Monophosphate