Aliases for PRKAA1 Gene
- Protein Kinase, AMP-Activated, Alpha 1 Catalytic Subunit 2 3
- Hydroxymethylglutaryl-CoA Reductase Kinase 3 4
- Acetyl-CoA Carboxylase Kinase 3 4
- Tau-Protein Kinase PRKAA1 3 4
- AMPK Subunit Alpha-1 3 4
- ACACA Kinase 3 4
- HMGCR Kinase 3 4
- EC 184.108.40.206 4 64
- AMPK 2 3
- 5-AMP-Activated Protein Kinase Catalytic Subunit Alpha-1 3
- 5-AMP-Activated Protein Kinase, Catalytic Alpha-1 Chain 3
- AMP-Activated Protein Kinase, Catalytic, Alpha-1 3
External Ids for PRKAA1 Gene
The protein encoded by this gene belongs to the ser/thr protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
GeneCards Summary for PRKAA1 Gene
PRKAA1 (Protein Kinase, AMP-Activated, Alpha 1 Catalytic Subunit) is a Protein Coding gene. Diseases associated with PRKAA1 include wolff-parkinson-white syndrome and obesity. Among its related pathways are PI3K-Akt signaling pathway and Signaling by GPCR. GO annotations related to this gene include chromatin binding and protein C-terminus binding. An important paralog of this gene is NUAK1.
UniProtKB/Swiss-Prot for PRKAA1 Gene
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.
AMP-activated protein kinase (AMPK) is a heterodimeric protein serine/threonine kinase that is composed of alpha- (catalytic) and beta/gamma- (regulatory) subunits. AMPK acts as a sensor of the energy status of cells and ensures survival at times of metabolic stress. AMPK phosphorylates many metabolic enzymes to stimulate catabolic pathways, such as ketogenesis, and inhibit anabolic pathways, such as protein synthesis. The long-term activation of AMPK increases the capacity of cells to produce ATP. AMPK is regulated by phosphorylation at the Thr-172 residue of the alpha-subunit by AMPKK and by phosphorylation by calmodulin-dependent protein kinase kinase-beta (CamKKbeta). In addition, the ratio of AMP:ATP mediates allosteric activation of the enzyme. AMPK is found throughout the body with high concentrations in metabolically active tissues such as the skeletal muscles and liver.