AMPKA2 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. Involved in insulin receptor/INSR internalization. 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. In that process also activates WDR45. 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 phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation. Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. Note: This description may include information from UniProtKB.
Protein type: AMPK subfamily; Autophagy; CAMK group; CAMKL family; EC; EC; EC; Kinase, protein; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor)
Chromosomal Location of human Ortholog: 1p32.2
Cellular Component:  axon; cytoplasmic stress granule; cytosol; dendrite; Golgi apparatus; neuronal cell body; nuclear speck; nucleoplasm; nucleus
Molecular Function:  [acetyl-CoA carboxylase] kinase activity; [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity; AMP-activated protein kinase activity; ATP binding; chromatin binding; histone serine kinase activity; metal ion binding; protein binding; protein kinase activity; protein serine/threonine kinase activity; protein serine/threonine/tyrosine kinase activity
Biological Process:  carnitine shuttle; cell cycle arrest; cellular response to calcium ion; cellular response to drug; cellular response to glucose starvation; cellular response to glucose stimulus; cellular response to nutrient levels; cellular response to oxidative stress; cellular response to prostaglandin E stimulus; cholesterol biosynthetic process; energy homeostasis; fatty acid biosynthetic process; fatty acid homeostasis; glucose homeostasis; histone-serine phosphorylation; lipid biosynthetic process; macroautophagy; negative regulation of apoptotic process; negative regulation of gene expression; negative regulation of TOR signaling; negative regulation of tubulin deacetylation; positive regulation of autophagy; positive regulation of cellular protein localization; positive regulation of glycolytic process; positive regulation of macroautophagy; positive regulation of peptidyl-lysine acetylation; regulation of circadian rhythm; regulation of fatty acid biosynthetic process; regulation of macroautophagy; regulation of microtubule cytoskeleton organization; regulation of signal transduction by p53 class mediator; regulation of stress granule assembly; response to muscle activity; rhythmic process; signal transduction; Wnt signaling pathway
Reference #:  P54646 (UniProtKB)
Alt. Names/Synonyms: 5'-AMP-activated protein kinase catalytic subunit alpha-2; 5'-AMP-activated protein kinase, catalytic alpha-2 chain; AAPK2; ACACA kinase; Acetyl-CoA carboxylase kinase; AMP-activated protein kinase alpha-2 subunit variant 2; AMP-activated protein kinase alpha-2 subunit variant 3; AMPK; AMPK alpha 2; AMPK subunit alpha-2; AMPK-alpha-2 chain; AMPK2; AMPKA2; HMGCR kinase; Hydroxymethylglutaryl-CoA reductase kinase; PRKAA; PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2; protein kinase, AMP-activated, alpha 2 catalytic subunit
Gene Symbols: PRKAA2
Molecular weight: 62,320 Da
Basal Isoelectric point: 7.65  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Autophagy Signaling  |  Insulin Receptor Signaling  |  mTOR Signaling  |  Translation: eIF4E and p70S6K  |  Warburg Effect
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene