a catalytic subunit of AMP-activated protein kinase (AMPK). Acts as an energy sensor, playing a key role in regulating cellular energy metabolism. A protein kinase of the CAMKL family whose activation is regulated by the balance between ADP/AMP/ATP, and intracellular Ca(2+) levels. Acts as a metabolic stress-sensing protein kinase switching off biosynthetic pathways when cellular ATP levels are depleted and when 5'-ADP and -AMP rise in response to fuel limitation and/or hypoxia. Activates energy-producing pathways and inhibits energy-consuming processes. Restores ATP levels in cells by switching off anabolic and switching on catabolic pathways. Activated primarily by rising ADP levels and not, as previously thought, solely by AMP. AMPK resembles an adenylate charge regulatory system in which anabolic and catabolic pathways are regulated by adenine nucleotide ratios. Acts via direct phosphorylation of metabolic enzymes and transcription regulators. Regulates fatty acid synthesis by phosphorylating acetyl-CoA carboxylase. Regulates cholesterol synthesis by phosphorylating and inactivating hormone-sensitive lipase and hydroxymethylglutaryl-CoA reductase. Activated by at least two distinct upstream kinases: the tumor suppressor LKB1 and CaMKK2. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton, probably by indirectly activating myosin. AMPK is a heterotrimer of an alpha catalytic subunit (AMPKA1 or -2), a beta (AMPKB1 or -2) and a gamma non-catalytic subunit (AMPKG1, -2 or -3). Different possible combinations of subunits give rise to 12 different holoenzymes. Binding of ADP or AMP to non-catalytic gamma subunit (PRKAG1, -2 or -3) results in allosteric activation. 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. 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. Salicylate/aspirin directly activates kinase activity. Studies in the mouse suggest that AMPK2 may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia. Note: This description may include information from UniProtKB.
Protein type: Kinase, protein; EC 22.214.171.124; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor); Autophagy; CAMK group; CAMKL family; AMPK subfamily
Cellular Component: nucleoplasm; cytosol
Molecular Function: AMP-activated protein kinase activity; protein serine/threonine kinase activity; protein binding; metal ion binding; [acetyl-CoA carboxylase] kinase activity; protein serine/threonine/tyrosine kinase activity; histone serine kinase activity; chromatin binding; ATP binding; [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity; protein kinase activity
Biological Process: negative regulation of TOR signaling pathway; Wnt receptor signaling pathway; transcription, DNA-dependent; lipid biosynthetic process; rhythmic process; cellular lipid metabolic process; carnitine shuttle; regulation of circadian rhythm; glucose homeostasis; signal transduction; protein amino acid phosphorylation; cholesterol biosynthetic process; cellular response to glucose starvation; cellular response to nutrient levels; regulation of fatty acid biosynthetic process; regulation of transcription, DNA-dependent; fatty acid homeostasis; positive regulation of glycolysis; insulin receptor signaling pathway; energy reserve metabolic process; response to stress; autophagy; cell cycle arrest; positive regulation of autophagy; fatty acid biosynthetic process; negative regulation of apoptosis
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.