AMPKA1: 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 a number of metabolic enzymes and transcription regulators. 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. Two isoforms of the human protein are produced by alternative splicing.
Protein type: Autophagy; EC 2.7.11.26; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor); Kinase, protein; EC 2.7.11.31; EC 2.7.11.27; EC 2.7.11.1; CAMK group; CAMKL family; AMPK subfamily
Chromosomal Location of Human Ortholog: 5p12
Cellular Component: nucleoplasm; cytoplasm; apical plasma membrane; intracellular; cytosol; nucleus; AMP-activated protein kinase complex
Molecular Function: AMP-activated protein kinase activity; protein C-terminus binding; cAMP-dependent protein kinase activity; metal ion binding; [acetyl-CoA carboxylase] kinase activity; histone serine kinase activity; protein kinase activity; protein binding; tau-protein kinase activity; chromatin binding; kinase binding; ATP binding; [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
Biological Process: protein heterooligomerization; activation of MAPK activity; lipid biosynthetic process; rhythmic process; positive regulation of cholesterol biosynthetic process; signal transduction; glucose homeostasis; protein amino acid phosphorylation; response to caffeine; cellular response to glucose starvation; cellular response to nutrient levels; negative regulation of lipid catabolic process; regulation of transcription, DNA-dependent; positive regulation of cell proliferation; response to gamma radiation; cell cycle arrest; negative regulation of glucosylceramide biosynthetic process; fatty acid biosynthetic process; positive regulation of autophagy; response to UV; negative regulation of TOR signaling pathway; Wnt receptor signaling pathway; transcription, DNA-dependent; glucose metabolic process; regulation of circadian rhythm; cholesterol biosynthetic process; fatty acid homeostasis; cold acclimation; positive regulation of glycolysis; insulin receptor signaling pathway; response to hypoxia; autophagy; fatty acid oxidation; response to activity; negative regulation of apoptosis
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