| IED ID | IndEnz0005001360 |
| Enzyme Type ID | lipase001360 |
| Protein Name |
5'-AMP-activated protein kinase catalytic subunit alpha-1 AMPK subunit alpha-1 EC 2.7.11.1 AMPK 63 kDa subunit Acetyl-CoA carboxylase kinase ACACA kinase EC 2.7.11.27 Hydroxymethylglutaryl-CoA reductase kinase HMGCR kinase EC 2.7.11.31 Tau-protein kinase PRKAA1 EC 2.7.11.26 Fragments |
| Gene Name | PRKAA1 AMPK1 |
| Organism | Sus scrofa (Pig) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Laurasiatheria Artiodactyla Suina Suidae (pigs) Sus Sus scrofa (Pig) |
| Enzyme Sequence | DGRVKIGHYILGDTLGVGTFGKRREIQNLKLFRHPHIIKLYQVISTPSDIFMVMEYVSGGELFDYICKNGRLDEKESRRLFQQILSGVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDDHVPTLFKKICDGIFYTPQYLNPSVISLLKHMLQVDPMKRATIKDIREHEWFKQDLPKYLFPEDPSYSXTMIDDEALKQDPLAVAYHLIIDNRDFYLATSPPDSFLDDHHLTRVPFLVAETPRDELNPQKXKHQGVRKAKXHLGIRQLDYEXKVVNPYYLRVRRKKMSLQLYQVDSRTYLLDFRSIDDXIDAEAQGKSSEASLTXSVT |
| Enzyme Length | 385 |
| Uniprot Accession Number | Q09136 |
| Absorption | |
| Active Site | ACT_SITE 100; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10027" |
| Activity Regulation | ACTIVITY REGULATION: Activated by phosphorylation on Thr-133. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-133. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-133. ADP also stimulates Thr-133 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-133, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. 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 (By similarity). {ECO:0000250|UniProtKB:Q13131}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P54645}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P54645}; CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[acetyl-CoA carboxylase] = ADP + H(+) + O-phospho-L-seryl-[acetyl-CoA carboxylase]; Xref=Rhea:RHEA:20333, Rhea:RHEA-COMP:13722, Rhea:RHEA-COMP:13723, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.27; Evidence={ECO:0000250|UniProtKB:P54645}; CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A reductase] = ADP + H(+) + O-phospho-L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A reductase]; Xref=Rhea:RHEA:23172, Rhea:RHEA-COMP:13692, Rhea:RHEA-COMP:13693, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.31; Evidence={ECO:0000250|UniProtKB:P54645}; CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-[tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26; Evidence={ECO:0000250|UniProtKB:P54645}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703, Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.26; Evidence={ECO:0000250|UniProtKB:P54645}; |
| DNA Binding | |
| EC Number | 2.7.11.1; 2.7.11.27; 2.7.11.31; 2.7.11.26 |
| Enzyme Function | FUNCTION: Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:7905477). 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 (By similarity). 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 (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (By similarity). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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/WIPI4. Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (By similarity). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (By similarity). 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 (By similarity). 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 (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (By similarity). {ECO:0000250|UniProtKB:P54645, ECO:0000250|UniProtKB:Q13131, ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:7905477}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 15..>22; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Features | Active site (1); Chain (1); Domain (1); Modified residue (10); Non-adjacent residues (9); Non-terminal residue (2); Nucleotide binding (1); Region (1) |
| Keywords | ATP-binding;Autophagy;Biological rhythms;Cholesterol biosynthesis;Cholesterol metabolism;Chromatin regulator;Cytoplasm;Direct protein sequencing;Fatty acid biosynthesis;Fatty acid metabolism;Kinase;Lipid biosynthesis;Lipid metabolism;Magnesium;Metal-binding;Nucleotide-binding;Nucleus;Phosphoprotein;Reference proteome;Serine/threonine-protein kinase;Steroid biosynthesis;Steroid metabolism;Sterol biosynthesis;Sterol metabolism;Transcription;Transcription regulation;Transferase;Ubl conjugation;Wnt signaling pathway |
| Interact With | |
| Induction | INDUCTION: By AMP. {ECO:0000269|PubMed:8557660}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13131}. Nucleus {ECO:0000250|UniProtKB:Q13131}. Note=In response to stress, recruited by p53/TP53 to specific promoters. {ECO:0000250|UniProtKB:Q13131}. |
| Modified Residue | MOD_RES 14; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:Q13131; MOD_RES 133; /note=Phosphothreonine; by LKB1 and CaMKK2; /evidence=ECO:0000250|UniProtKB:Q5EG47; MOD_RES 219; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:P54645; MOD_RES 276; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:Q13131; MOD_RES 277; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q13131; MOD_RES 281; /note=Phosphoserine; by ULK1; /evidence=ECO:0000250|UniProtKB:P54645; MOD_RES 289; /note=Phosphothreonine; by ULK1; /evidence=ECO:0000250|UniProtKB:P54645; MOD_RES 298; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:Q13131; MOD_RES 353; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q13131; MOD_RES 383; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q13131 |
| Post Translational Modification | PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q5EG47}.; PTM: Phosphorylated at Thr-133 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-133 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-133, but at a much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK (By similarity). Dephosphorylated by PPM1A and PPM1B (By similarity). {ECO:0000250|UniProtKB:Q13131}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 44,226 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:17989; RHEA:46608; RHEA:20333; RHEA:23172; RHEA:12801; RHEA:53904 |
| Cross Reference Brenda |