PRKAA2
Description
The PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) is a protein-coding gene located on chromosome 1.
5'-AMP-activated protein kinase catalytic subunit alpha-2 is an enzyme that in humans is encoded by the PRKAA2 gene.
== Function == The protein encoded by this gene is a catalytic subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. Studies of the mouse counterpart suggest that this catalytic subunit may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia.
The PRKAA2 gene encodes the catalytic subunit alpha-2 of AMP-activated protein kinase (AMPK), a key regulator of cellular energy metabolism. AMPK is activated in response to reduced intracellular ATP levels, triggering energy-producing pathways and inhibiting energy-consuming processes like protein, carbohydrate, and lipid biosynthesis, as well as cell growth and proliferation. AMPK functions by directly phosphorylating metabolic enzymes and through long-term effects via phosphorylation of transcription regulators. It regulates lipid synthesis by inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR, and LIPE, controlling fatty acid and cholesterol synthesis. AMPK promotes lipolysis of lipid droplets by phosphorylating CHKA (CHKalpha2). It regulates insulin signaling and glycolysis by phosphorylating IRS1, PFKFB2, and PFKFB3. AMPK also plays a role in insulin receptor/INSR internalization and stimulates glucose uptake in muscle by promoting the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane. AMPK 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. AMPK acts as a key regulator of glucose homeostasis in the liver and promotes transcription in response to stress by phosphorylating histone H2B. It also regulates cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24, and ATG1/ULK1. AMPK promotes autophagy in response to nutrient limitation by activating ATG1/ULK1 and WDR45/WIPI4. It inhibits CASP6 autoprocessing and activation. AMPK acts as a regulator of circadian rhythm by mediating the phosphorylation of CRY1 and may regulate the Wnt signaling pathway by phosphorylating CTNNB1. It also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Additionally, AMPK phosphorylates CFTR, EEF2K, KLC1, NOS3, and SLC12A1. AMPK plays a critical role in the differential regulation of pro-autophagy and non-autophagy complexes in response to glucose starvation. AMPK promotes ARF6 activation upon glucose starvation leading to cell migration. It also mediates the phosphorylation of ACSS2 upon glucose deprivation. AMPK regulates mitochondrial fragmentation through phosphorylation of MTFR1L in response to stress. AMPK is a heterotrimer composed of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2), and a gamma non-catalytic subunit (PRKAG1, PRKAG2, or PRKAG3). It interacts with FNIP1, FNIP2, and ARF6. PRKAA2/AMPK2, together with ATIC and HACD3/PTPLAD1, is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis.
PRKAA2 is also known as AMPK, AMPK2, AMPKa2, PRKAA.
