Any feedback?
Information on EC 2.7.11.31 - [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase and Organism(s) Homo sapiens and UniProt Accession P54646
for references in articles please use BRENDA:EC2.7.11.31Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinaseIUBMB Comments
The enzyme is activated by AMP. EC 1.1.1.34, hydroxymethylglutaryl-CoA reductase (NADPH) is inactivated by the phosphorylation of the enzyme protein. Histones can also act as acceptors. The enzyme can also phosphorylate hepatic acetyl-CoA carboxylase (EC 6.4.1.2) and adipose hormone-sensitive lipase (EC 3.1.1.79) . Thr-172 within the catalytic subunit (alpha-subunit) is the major site phosphorylated by the AMP-activated protein kinase kinase . GTP can act instead of ATP
Specify your search results
Word Map
- 2.7.11.31
- metformin
- rapamycin
- peroxisome
- obesity
- aicar
- mtor
- carboxylase
-
proliferator-activated
- acetyl-coa
- endothelial
- cardiac
-
high-fat
- triglyceride
- adipocytes
- adiponectin
- glycogen
- agonist
- mellitus
-
obese
- sterol
- hypothalamic
- steatosis
- sirt1
-
antidiabetic
-
ampk-dependent
-
diet-induced
- sirtuins
- leptin
-
p-ampk
- 5-aminoimidazole-4-carboxamide
-
lipogenesis
-
insulin-stimulated
-
ampk-mediated
- myotubes
-
element-binding
-
hfd-induced
-
anti-obesity
- srebp-1c
- ulk1
- camkks
-
adipor1
- coactivator-1
-
palmitoyltransferase-1
- dorsomorphin
- drug development
-
phospho-ampk
- epitrochlearis
-
metformin-induced
- phenformin
-
energy-sensing
-
insulin-independent
- medicine
- industry
- pharmacology
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
adenosine monophosphate-activated protein kinase, amp-activated kinase, 5'-amp-activated protein kinase, prkaa1, snf1 kinase, adenosine 5'-monophosphate-activated protein kinase, ampkalpha1, reductase kinase, aak-2, ampk alpha2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3-hydroxy-3-methylglutaryl coenzyme A reductase kinase
-
-
-
-
3-hydroxy-3-methylglutaryl-CoA reductase kinase
-
-
-
-
AMP-activated protein kinase
AMPK
AMPKalpha
beta-hydroxy-beta-methylglutaryl-CoA reductase kinase
-
-
-
-
hydroxymethylglutaryl coenzyme A reductase kinase
-
-
-
-
hydroxymethylglutaryl coenzyme A reductase kinase (phosphorylating)
-
-
-
-
reductase kinase
-
-
-
-
[hydroxymethylglutaryl-CoA reductase (NADPH2)] kinase
-
-
-
-
AMP-activated protein kinase
-
-
-
-
AMP-activated protein kinase
-
-
AMPK
-
-
-
-
AMPK
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:[hydroxymethylglutaryl-CoA reductase (NADPH)] phosphotransferase
The enzyme is activated by AMP. EC 1.1.1.34, hydroxymethylglutaryl-CoA reductase (NADPH) is inactivated by the phosphorylation of the enzyme protein. Histones can also act as acceptors. The enzyme can also phosphorylate hepatic acetyl-CoA carboxylase (EC 6.4.1.2) and adipose hormone-sensitive lipase (EC 3.1.1.79) [5]. Thr-172 within the catalytic subunit (alpha-subunit) is the major site phosphorylated by the AMP-activated protein kinase kinase [7]. GTP can act instead of ATP [4]
CAS REGISTRY NUMBER
COMMENTARY
172522-01-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + [acetyl-CoA carboxylase]
ADP + [acetyl-CoA carboxylase] phosphate
phosphorylation at Ser79
-
-
?
ATP + 3-mercaptopyruvate sulfurtransferase
ADP + phosphorylated 3-mercaptopyruvate sulfurtransferase
-
-
-
?
ATP + acylamino-acid-releasing enzyme
ADP + phosphorylated acylamino-acid-releasing enzyme
-
-
-
?
ATP + adenylate kinase isoenzyme 1
ADP + phosphorylated adenylate kinase isoenzyme 1
-
-
-
?
ATP + adipose hormone-sensitive lipase
ADP + adipose hormone-sensitive lipase phosphate
-
-
-
-
?
ATP + adipose hormone-sensitive lipase
ADP + [adipose hormone-sensitive lipase] phosphate
-
-
-
-
?
ATP + band 3 anion transport protein
ADP + phosphorylated band 3 anion transport protein
-
-
-
?
ATP + bisphosphoglycerate mutase
ADP + phosphorylated bisphosphoglycerate mutase
-
-
-
?
ATP + carbonic anhydrase 1
ADP + phosphorylated carbonic anhydrase 1
-
-
-
?
ATP + cytoplasmic malate dehydrogenase
ADP + phosphorylated cytoplasmic malate dehydrogenase
-
-
-
?
ATP + dihydropteridine reductase
ADP + phosphorylated dihydropteridine reductase
-
-
-
?
ATP + DNA damage-binding protein 1
ADP + phosphorylated DNA damage-binding protein 1
-
-
-
?
ATP + erythrocyte spectrin alpha chain
ADP + phosphorylated erythrocyte spectrin alpha chain
-
-
-
?
ATP + erythrocyte spectrin beta chain
ADP + phosphorylated erythrocyte spectrin beta chain
-
-
-
?
ATP + eukaryotic elongation factor 2 kinase
ADP + phosphorylated eukaryotic elongation factor 2 kinase
ATP + glutathione S-transferase omega-1
ADP + phosphorylated glutathione S-transferase omega-1
-
-
-
?
ATP + glutathione synthetase
ADP + phosphorylated glutathione synthetase
-
-
-
?
ATP + PFK2
ADP + phospho-PFK2
-
phosphorylation at Ser466 induced by UV radiation and H2O2 treatment
-
-
?
ATP + phosphoglycerate kinase 1
ADP + phosphorylated phosphoglycerate kinase 1
-
-
-
?
ATP + phosphoribosylformylglycinamidine synthase
ADP + phosphorylated phosphoribosylformylglycinamidine synthase
-
-
-
?
ATP + PKZeta
?
-
AMPK alpha phosphorylates PKZeta on residue Thr410 within the PKCzeta activation loop
-
-
?
ATP + proteasome subunit alpha type-1
ADP + phosphorylated proteasome subunit alpha type-1
-
-
-
?
ATP + proteasome subunit alpha type-7
ADP + phosphorylated proteasome subunit alpha type-7
-
-
-
?
ATP + purine nucleoside phosphorylase
ADP + phosphorylated purine nucleoside phosphorylase
-
-
-
?
ATP + RNA-binding protein HUR
ADP + ?
-
inhibits the protein by phosphorylation
-
-
?
ATP + S-formylglutathione hydrolase
ADP + phosphorylated S-formylglutathione hydrolase
-
-
-
?
ATP + selenium binding protein 1
ADP + phosphorylated selenium binding protein 1
-
-
-
?
ATP + thioredoxin-like protein 1
ADP + phosphorylated thioredoxin-like protein 1
-
-
-
?
ATP + ubiquitin carboxyl-terminal hydrolase 13
ADP + phosphorylated ubiquitin carboxyl-terminal hydrolase 13
-
-
-
?
ATP + ubiquitin carboxyl-terminal hydrolase 14
ADP + phosphorylated ubiquitin carboxyl-terminal hydrolase 14
-
-
-
?
ATP + ubiquitin carboxyl-terminal hydrolase 5
ADP + phosphorylated ubiquitin carboxyl-terminal hydrolase 5
-
-
-
?
ATP + ubiquitin-activating enzyme E1
ADP + phosphorylated ubiquitin-activating enzyme E1
-
-
-
?
ATP + valosin-containing protein
ADP + phosphorylated valosin-containing protein
-
-
-
?
ATP + [acetyl-CoA carboxylase]
ADP + phospho-[acetyl-CoA carboxylase]
-
phosphorylation at Ser79
-
-
?
ATP + [endothelial nitic oxide synthase]
ADP + [endothelial nitic oxide synthase] phosphate
ATP + [endothelial nitric oxide synthase]
ADP + [endothelial nitric oxide synthase] phosphate
ATP + [Golgi-specific brefeldin A resistance factor 1]
ADP + [Golgi-specific brefeldin A resistance factor 1] phosphate
ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)]
ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate
ATP + [peptide HMRSAMSGLHLVKRR]
ADP + [peptide HMRSAMSGLHLVKRR] phosphate
-
i.e. SAMS peptide
-
-
?
ATP + acetyl-CoA carboxylase
ADP + phosphorylated acetyl-CoA carboxylase
-
-
-
-
?
ATP + acetyl-CoA carboxylase
ADP + phosphorylated acetyl-CoA carboxylase
-
the enzyme is involved in the regulation of hepatic lipids via its downstream effector acetyl-CoA carboxylase, enzyme inhibition leads to an increased level of triacylglycerols and accumulation of lipids, metformin decreases lipid accumulation, induced by high D-glucose levels, by activating the enzyme, the enzyme functions as energy intracellular sensor
-
-
?
ATP + acetyl-CoA carboxylase
ADP + phosphorylated acetyl-CoA carboxylase
-
phosphorylation at Ser79, phosphorylation inhibits the acetyl-CoA carboxylase
-
-
?
ATP + acetyl-CoA carboxylase
ADP + [acetyl-CoA carboxylase] phosphate
-
-
-
?
ATP + acetyl-CoA carboxylase
ADP + [acetyl-CoA carboxylase] phosphate
-
-
-
?
ATP + acetyl-CoA carboxylase
ADP + [acetyl-CoA carboxylase] phosphate
-
-
-
?
ATP + acetyl-CoA carboxylase
ADP + [acetyl-CoA carboxylase] phosphate
-
AMPK plays an important role in regulating malonyl-CoA levels through the phosphorylation of acetyl-CoA carboxylase
-
?
ATP + acetyl-CoA carboxylase
ADP + [acetyl-CoA carboxylase]phosphate
-
AMPK alpha phosphorylates at Ser79
-
-
?
ATP + acetyl-CoA carboxylase
ADP + [acetyl-CoA carboxylase]phosphate
-
AMPKalpha can phosphorylate Ser79 of acetyl-CoA carboxylase
-
-
?
ATP + biotin-GGHMRSAMSGLHLVKRR-NH2
ADP + phosphorylated biotin-GGHMRSAMpSGLHLVKRR-NH2
i.e. SAMS peptide, a peptide derived from residues 73-85 of rat acetyl-CoA carboxylase in which Ser77 is mutated to Ala and the AMPK phosphorylation site is Ser79
-
-
?
ATP + biotin-GGHMRSAMSGLHLVKRR-NH2
ADP + phosphorylated biotin-GGHMRSAMpSGLHLVKRR-NH2
i.e. SAMS peptide, a peptide derived from residues 73-85 of rat acetyl-CoA carboxylase in which Ser77 is mutated to Ala and the AMPK phosphorylation site is Ser79
-
-
?
ATP + eukaryotic elongation factor 2 kinase
ADP + phosphorylated eukaryotic elongation factor 2 kinase
-
phosphorylation at Ser398, the enzyme plays a regulatory role in eEF2 kinase activity, overview
-
-
?
ATP + eukaryotic elongation factor 2 kinase
ADP + phosphorylated eukaryotic elongation factor 2 kinase
-
phosphorylation at Ser398 activates the eukaryotic elongation factor 2 kinase, no activity with the substrate mutant S398A
-
-
?
ATP + HMRSAMSGLHLVKRR
ADP + ?
-
synthetic SAMS-containing peptide as substrate
-
-
?
ATP + HMRSAMSGLHLVKRR
ADP + ?
-
acetyl-CoA carboxylase-derived synthetic peptide substrate
-
-
?
ATP + p38
ADP + phospho-p38
-
phosphorylation at Thr180/Thr182, p38 MAPK is a downstream signal of AMPK upon various stimuli, AMPK serves as a positive regulator for p38 Ser15 phosphorylation induced by UV radiation and H2O2 treatment
-
-
?
ATP + p53
ADP + phospho-p53
-
AMPK serves as a positive regulator for p38 Ser15 phosphorylation induced by UV radiation and H2O2 treatment
-
-
?
ATP + ubiquitin ligase Nedd4-2
ADP + phosphorylated ubiquitin ligase Nedd4-2
Q13131; Q9Y478; P54619
-
-
-
?
ATP + ubiquitin ligase Nedd4-2
ADP + phosphorylated ubiquitin ligase Nedd4-2
Q13131; Q9Y478; P54619
activation
-
-
?
ATP + [acetyl-CoA carboxylase]
ADP + [acetyl-CoA carboxylase] phosphate
-
-
-
-
?
ATP + [acetyl-CoA carboxylase]
ADP + [acetyl-CoA carboxylase] phosphate
-
phosphorylation at Ser79
-
-
?
ATP + [acetyl-CoA carboxylase]
ADP + [acetyl-CoA carboxylase] phosphate
phosphorylation at Ser79
-
-
?
ATP + [endothelial nitic oxide synthase]
ADP + [endothelial nitic oxide synthase] phosphate
-
activates nitric oxide synthesis, mechanism, overview
-
-
?
ATP + [endothelial nitic oxide synthase]
ADP + [endothelial nitic oxide synthase] phosphate
-
phosphorylation by AMPK at Ser1177
-
-
?
ATP + [endothelial nitric oxide synthase]
ADP + [endothelial nitric oxide synthase] phosphate
-
AMPK-eNOS signalling, overview
-
-
?
ATP + [endothelial nitric oxide synthase]
ADP + [endothelial nitric oxide synthase] phosphate
-
phosphorylation at Ser1177
-
-
?
ATP + [Golgi-specific brefeldin A resistance factor 1]
ADP + [Golgi-specific brefeldin A resistance factor 1] phosphate
-
phosphorylation at Thr1337 to induce disassembly of Golgi apparatus
-
-
?
ATP + [Golgi-specific brefeldin A resistance factor 1]
ADP + [Golgi-specific brefeldin A resistance factor 1] phosphate
-
a guanine nucleotide exchange factor for the ADP-ribosylation factor family associated with the Golgi apparatus, phosphorylation at Thr1337, phosphorylation site identification by mutational analysis
-
-
?
ATP + [histone deacetylase 5]
ADP + [histone deacetylase 5] phosphate
-
AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5
-
-
?
ATP + [histone deacetylase 5]
ADP + [histone deacetylase 5] phosphate
-
phosphorylation at Ser259 and Ser498
-
-
?
ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)]
ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate
-
-
-
?
ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)]
ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate
-
-
-
-
?
additional information
?
-
-
conditions that elevate the AMP:ATP ratio in cells, such as growth factor depletion, hypoglycemia, ischemia in heart muscle, exercise in skeletal muscle, as well as treatment with arsenite, azide, oxidative agents and the pharmacological agent AICAR, which mimics the effect of AMP can cause activation of AMPK
-
-
?
additional information
?
-
-
phosphorylates key target proteins that control flux through metabolic pathways of hepatic ketogenesis, cholesterol synthesis, adipocyte lipolysis and skeletal muscle fatty acid oxidation
-
-
?
additional information
?
-
-
AMP-activated protein kinase acts as a key energy sensor in regulating intracellular lysosomal protein degradation and is involved in proteasomal degradation of proteins, which allows the regulation of proteasomal activity under conditions of energy demand, mechanism, overview
-
-
?
additional information
?
-
-
AMP-activated protein kinase acts as a master regulator of cellular metabolism in skeletal muscle, biochemical regulation of AMPK by AMP, protein phosphatases, and its three known upstream kinases, LKB1, Ca2+/calmodulin-dependent protein kinase kinase, CaMKK, and transforming growth factor-beta activated kinase 1, TAK1. Physiological regulation of cellular metabolism in skeletal muscle, concerning glucose metabolism, glycogen synthesis, protein metabolism and degradation, lipid metabolism and lipolysis, detailed overview
-
-
?
additional information
?
-
-
AMP-activated protein kinase contributes to UV- and H2O2-induced apoptosis in human skin keratinocytes, AMPK serves as a negative feedback signal against UV-induced mammalian target of rapamycin, mTOR activation in a TSC2-dependent manner, AMPK plays important roles in UV-induced signal transduction ultimately leading to skin photoaging and even skin cancer, regulation, overview
-
-
?
additional information
?
-
-
AMP-activated protein kinase is involved in 8-chloro-cAMP-induced growth inhibition which proceeds via p38 MAPK and the metabolite 8-chloro-adenosine, AICAR must be phosphorylated to ZMP by adenosine kinases in order to activate AMPK, mechanism, overview
-
-
?
additional information
?
-
-
AMP-activated protein kinase is involved in regulation of the activation of the PGC-1alpha promoter and PGC-1alpha expression in skeletal muscle cells, effect of AMPK activation on DNA binding and protein expression, overview
-
-
?
additional information
?
-
-
AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes representing a mechanism in Cushings syndrome, overview. activation of AMPK stimulates appetite in the hypothalamus and stimulates catabolic processes in the periphery
-
-
?
additional information
?
-
-
AMPK is a sensor of the cellular energy status, it also exerts modulation of the fibrogenic properties of hepatic stellate cells, physiological effects of AMPK activation and inhibition, mechanism, AMPK activation regulates intracellular signaling pathways in hepatic stellate cells, overview
-
-
?
additional information
?
-
-
AMPK is activated in response to changes in the cellular energy charge and cellular stress via increases in the ATP-to-AMP ratio
-
-
?
additional information
?
-
-
AMPK regulates the energy balance both at the cellular and whole body level, disorders of it are obesity, type 2 diabetes and the metabolic syndrome, overview. Activating mutations in AMPK can cause heart disease. AMPK is regulated by the AMP/ATP ratio and upstream kinases, e.g. CaMKKbeta and LBK1, overview. AMPK activation inhibits activation of the mammalian target-of-rapamycin pathway by the insulin/insulin-like growth factor-1 pathway, probably via phosphorylation of TSC2, an upstream regulator of mTOR
-
-
?
additional information
?
-
-
AMPK signaling influences glucose and lipid metabolisms, mitochondrial biogenesis, and gene transcription, playing a role in trained and obese physiological state, overview. AMPK is important in the molecular regulation of lipid oxidation in skeletal muscle and the energy balance through suppression of ATP-consuming anabolic pathways and enhancement of ATP-producing catabolic pathways, overview
-
-
?
additional information
?
-
-
lovostatin-induced endothelial progenitor cell to endothelial cell differentiation depends on AMPK, AMPK enhances the vasculogensis and angiogenesis of endothelial progenitor cells, overview
-
-
?
additional information
?
-
-
AMPK phosphorylates histone deacetylase 5 (HDAC5) at Ser259 and Ser498 in primary myocytes
-
-
?
additional information
?
-
-
AMPK phosphorylates site 2 on glycogen synthase in cell-free assays
-
-
?
additional information
?
-
identification of putative AMPK targets in hemoglobin-depleted lysates of erythrocytes, including metabolic enzymes, cytoskeletal proteins and enzymes involved in the oxidative stress response, cloning and recombinant expression
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + [acetyl-CoA carboxylase]
ADP + [acetyl-CoA carboxylase] phosphate
phosphorylation at Ser79
-
-
?
ATP + eukaryotic elongation factor 2 kinase
ADP + phosphorylated eukaryotic elongation factor 2 kinase
-
phosphorylation at Ser398, the enzyme plays a regulatory role in eEF2 kinase activity, overview
-
-
?
ATP + p38
ADP + phospho-p38
-
phosphorylation at Thr180/Thr182, p38 MAPK is a downstream signal of AMPK upon various stimuli, AMPK serves as a positive regulator for p38 Ser15 phosphorylation induced by UV radiation and H2O2 treatment
-
-
?
ATP + p53
ADP + phospho-p53
-
AMPK serves as a positive regulator for p38 Ser15 phosphorylation induced by UV radiation and H2O2 treatment
-
-
?
ATP + PFK2
ADP + phospho-PFK2
-
phosphorylation at Ser466 induced by UV radiation and H2O2 treatment
-
-
?
ATP + ubiquitin ligase Nedd4-2
ADP + phosphorylated ubiquitin ligase Nedd4-2
Q13131; Q9Y478; P54619
activation
-
-
?
ATP + [acetyl-CoA carboxylase]
ADP + phospho-[acetyl-CoA carboxylase]
-
phosphorylation at Ser79
-
-
?
ATP + [endothelial nitic oxide synthase]
ADP + [endothelial nitic oxide synthase] phosphate
-
activates nitric oxide synthesis, mechanism, overview
-
-
?
ATP + [endothelial nitric oxide synthase]
ADP + [endothelial nitric oxide synthase] phosphate
-
AMPK-eNOS signalling, overview
-
-
?
ATP + [Golgi-specific brefeldin A resistance factor 1]
ADP + [Golgi-specific brefeldin A resistance factor 1] phosphate
-
phosphorylation at Thr1337 to induce disassembly of Golgi apparatus
-
-
?
ATP + [histone deacetylase 5]
ADP + [histone deacetylase 5] phosphate
-
AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5
-
-
?
ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)]
ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate
ATP + acetyl-CoA carboxylase
ADP + phosphorylated acetyl-CoA carboxylase
-
-
-
-
?
ATP + acetyl-CoA carboxylase
ADP + phosphorylated acetyl-CoA carboxylase
-
the enzyme is involved in the regulation of hepatic lipids via its downstream effector acetyl-CoA carboxylase, enzyme inhibition leads to an increased level of triacylglycerols and accumulation of lipids, metformin decreases lipid accumulation, induced by high D-glucose levels, by activating the enzyme, the enzyme functions as energy intracellular sensor
-
-
?
ATP + [acetyl-CoA carboxylase]
ADP + [acetyl-CoA carboxylase] phosphate
-
-
-
-
?
ATP + [acetyl-CoA carboxylase]
ADP + [acetyl-CoA carboxylase] phosphate
phosphorylation at Ser79
-
-
?
ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)]
ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate
-
-
-
?
ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)]
ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate
-
-
-
-
?
additional information
?
-
-
AMP-activated protein kinase acts as a key energy sensor in regulating intracellular lysosomal protein degradation and is involved in proteasomal degradation of proteins, which allows the regulation of proteasomal activity under conditions of energy demand, mechanism, overview
-
-
?
additional information
?
-
-
AMP-activated protein kinase acts as a master regulator of cellular metabolism in skeletal muscle, biochemical regulation of AMPK by AMP, protein phosphatases, and its three known upstream kinases, LKB1, Ca2+/calmodulin-dependent protein kinase kinase, CaMKK, and transforming growth factor-beta activated kinase 1, TAK1. Physiological regulation of cellular metabolism in skeletal muscle, concerning glucose metabolism, glycogen synthesis, protein metabolism and degradation, lipid metabolism and lipolysis, detailed overview
-
-
?
additional information
?
-
-
AMP-activated protein kinase contributes to UV- and H2O2-induced apoptosis in human skin keratinocytes, AMPK serves as a negative feedback signal against UV-induced mammalian target of rapamycin, mTOR activation in a TSC2-dependent manner, AMPK plays important roles in UV-induced signal transduction ultimately leading to skin photoaging and even skin cancer, regulation, overview
-
-
?
additional information
?
-
-
AMP-activated protein kinase is involved in 8-chloro-cAMP-induced growth inhibition which proceeds via p38 MAPK and the metabolite 8-chloro-adenosine, AICAR must be phosphorylated to ZMP by adenosine kinases in order to activate AMPK, mechanism, overview
-
-
?
additional information
?
-
-
AMP-activated protein kinase is involved in regulation of the activation of the PGC-1alpha promoter and PGC-1alpha expression in skeletal muscle cells, effect of AMPK activation on DNA binding and protein expression, overview
-
-
?
additional information
?
-
-
AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes representing a mechanism in Cushings syndrome, overview. activation of AMPK stimulates appetite in the hypothalamus and stimulates catabolic processes in the periphery
-
-
?
additional information
?
-
-
AMPK is a sensor of the cellular energy status, it also exerts modulation of the fibrogenic properties of hepatic stellate cells, physiological effects of AMPK activation and inhibition, mechanism, AMPK activation regulates intracellular signaling pathways in hepatic stellate cells, overview
-
-
?
additional information
?
-
-
AMPK is activated in response to changes in the cellular energy charge and cellular stress via increases in the ATP-to-AMP ratio
-
-
?
additional information
?
-
-
AMPK regulates the energy balance both at the cellular and whole body level, disorders of it are obesity, type 2 diabetes and the metabolic syndrome, overview. Activating mutations in AMPK can cause heart disease. AMPK is regulated by the AMP/ATP ratio and upstream kinases, e.g. CaMKKbeta and LBK1, overview. AMPK activation inhibits activation of the mammalian target-of-rapamycin pathway by the insulin/insulin-like growth factor-1 pathway, probably via phosphorylation of TSC2, an upstream regulator of mTOR
-
-
?
additional information
?
-
-
AMPK signaling influences glucose and lipid metabolisms, mitochondrial biogenesis, and gene transcription, playing a role in trained and obese physiological state, overview. AMPK is important in the molecular regulation of lipid oxidation in skeletal muscle and the energy balance through suppression of ATP-consuming anabolic pathways and enhancement of ATP-producing catabolic pathways, overview
-
-
?
additional information
?
-
-
lovostatin-induced endothelial progenitor cell to endothelial cell differentiation depends on AMPK, AMPK enhances the vasculogensis and angiogenesis of endothelial progenitor cells, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
increases in intracellular Ca2+ levels activate AMPK is via the activation of CaMKKs, mechanism, overview
Mg2+
Mg2+
-
-
Mg2+
-
Asp-157 within the DFG motif is required for binding the Mg2+ ion that co-ordinates beta and gamma phosphates of Mg2+-ATP in the active site
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(Z)-2-(3-((4-((2-(diethylamino)ethyl)carbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)ethyl acetate
-
-
(Z)-5-((5-(2-acetamidoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-5-((5-(2-azidoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-5-((5-(2-cyanoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-5-((5-(3-amino-3-oxopropyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
potent and selective inhibitor
(Z)-5-((5-cyano-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole3-carboxamide
-
-
(Z)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid
85% inhibition at 0.01 mM
(Z)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-N-propyl-1H-pyrrole-3-carboxamide
48% inhibition at 0.01 mM
(Z)-5-((6-bromo-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-5-((6-chloro-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-5-((2-oxo-5-(ureidomethyl)indolin-3-ylidene)methyl)-1H-pyrrole-3-carboxamide
-
-
(Z)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-5-((2-oxoindolin-3-ylidene)methyl)-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-5-((6-methyl-2-oxoindolin-3-ylidene)methyl)-1H-pyrrole-3-carboxamide
88% inhibition at 0.01 mM
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-(dimethylamino)ethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-hydroxyethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
potent and selective inhibitor
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-methoxyethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
-
(Z)-N-(2-(diethylamino)ethyl)-5-((5-fluoro-1-methyl-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
17% inhibition at 0.01 mM
(Z)-N-(2-(diethylamino)ethyl)-5-((6-ethyl-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
90% inhibition at 0.01 mM
(Z)-N-(2-(diethylamino)ethyl)-5-((6-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(diethylamino)ethyl)-5-((6-isopropyl-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
69% inhibition at 0.01 mM
(Z)-N-(2-(dimethylamino)ethyl)-5-((5-floro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(ethylamino)ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-aminoethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene) methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(3-(diethylamino)propyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(3-(dimethylamino)propyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
compound C
(6-[4-(2-piperidin-1-yl-ethoxy)-phenyl])-3-pyridin-4-yl-pyrazolo[1,5-a]pyrimidine, a selective inhibitor, inhibition of the AMP-activated protein kinase alpha2 subunit kinase domain. Compound C binding dramatically alters the conformation of the activation loop, which adopts an intermediate conformation between DFG-out and DFG-in. The induced fit forms a compound-C binding pocket composed of the N-lobe, the C-lobe and the hinge of the kinase domain. The pocket partially overlaps with the putative ATP-binding pocket. Binding structure analysis, overview
N-[2-(diethylamino)ethyl]-5-[(Z)-(6-fluoro-2-oxo-2,3-dihydro-1H-inden-1-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
sunitinib, subunit AMPKalpha2 shows 46% inhibition at 100 nM
STO 609
molecular docking study, STO 609 docks in the compound-C binding pocket of AMPK
(Z)-2-(3-((4-((2-(diethylamino)ethyl)carbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)ethyl acetate
-
-
(Z)-5-((5-(2-acetamidoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-5-((5-(2-azidoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-5-((5-(2-cyanoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-5-((5-(3-amino-3-oxopropyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
potent and selective inhibitor
(Z)-5-((5-cyano-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole3-carboxamide
-
-
(Z)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid
78% inhibition at 0.01 mM
(Z)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-N-propyl-1H-pyrrole-3-carboxamide
30% inhibition at 0.01 mM
(Z)-5-((6-bromo-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-5-((6-chloro-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-5-((2-oxo-5-(ureidomethyl)indolin-3-ylidene)methyl)-1H-pyrrole-3-carboxamide
-
-
(Z)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-5-((2-oxoindolin-3-ylidene)methyl)-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-5-((6-methyl-2-oxoindolin-3-ylidene)methyl)-1H-pyrrole-3-carboxamide
89% inhibition at 0.01 mM
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-(dimethylamino)ethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-hydroxyethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
potent and selective inhibitor
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-methoxyethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
-
(Z)-N-(2-(diethylamino)ethyl)-5-((5-fluoro-1-methyl-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
40% inhibition at 0.01 mM
(Z)-N-(2-(diethylamino)ethyl)-5-((6-ethyl-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(diethylamino)ethyl)-5-((6-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(diethylamino)ethyl)-5-((6-isopropyl-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
70% inhibition at 0.01 mM
(Z)-N-(2-(dimethylamino)ethyl)-5-((5-floro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-(ethylamino)ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(2-aminoethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene) methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(3-(diethylamino)propyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
(Z)-N-(3-(dimethylamino)propyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
-
dexamethasone
-
decreases in AMPK activity in treated adipocytes. The inhibitory effect of dexamethasone on AMPK activity is antagonized by co-administration of metformin at 0.01 mM, which increases AMPK activity to 224% compared with dexamethasone treatment alone
glucocorticoid
-
treatment inhibits AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus, similar to activity in vitro in the primary adipose and hypothalamic cells
-
N-[2-(diethylamino)ethyl]-5-[(Z)-(6-fluoro-2-oxo-2,3-dihydro-1H-inden-1-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
sunitinib, subunit AMPKalpha1 shows about 50% inhibition at 100 nM
nicotinamide
-
SIRT1 inhibitor, potentiates Tat-mediated reduction in AMPK activation and downstream acetyl-CoA carboxylase activation. Potentiates Tat-induced HIV-1 transactivation
6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine
-
compound C, AMPK inhibitor, reduces puerarin-induced suppression of MDR1 expression
6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine
-
compound C, AMPK-inhibitor, 0.02 mM does not significantly modify eryptosis under glucose-replete conditions but significantly augments the eryptotic effect of glucose withdrawal
6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine
-
compound C, hypoxia-induced PKCzeta translocation to the plasma membrane and phosphorylation at Thr410 is prevented by pharmacological inhibition of AMPK
6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine
-
compound C, inhibition of AMPK prevents at 0.05 mM, in part, the IFNgamma-induced decrease in transepithelial electrical resistance, the increased epithelial permeability, the decreased transepithelial electrical resistance, and the decrease in occludin and zonula occludens-1 caused by IFNgamma treatment of T84 cells
6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine
-
compound C, potent AMPK inhibitor, inhibition results in an increase in 1-methyl-4-pyridinium-induced cell death. Prevents the AMPK activation by 1-methyl-4-pyridinium and stimulates 1-methyl-4-pyridinium-induced cell death
6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine
-
compound C, potentiates Tat-induced HIV-1 transactivation
compound C
-
i.e. 6-[4-(2-piperidin-1-ylethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine, a cell-permeable pyrrazolopyrimidine compound that can act as a reversible and ATP competitive inhibitor of AMPK
compound C
-
i.e. AMPKi or 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine, a specific inhibitor of AMPK, largely impairs the activation of p38 MAPK upon UV radiation
compound C
-
i.e. dorsomorphin or 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine
additional information
-
insulin-resistance caused by high levels of D-glucose in the cell decreases the enzyme activity
-
additional information
-
activating phosphorylation of AMPK at Thr172 of the alpha-subunit, e.g. by CaMKKbeta or LBK1, inhibiting dephosphorylation by phosphatase PP2C
-
additional information
-
activation of p38 in response to UV or H2O2 is inhibited in AMPKalpha siRNA-treated HaCaT cells, EGFR inhibitor PD 153035 and AG 1478 inhibit UV-induced AMPK and LKB1 activation
-
additional information
-
physiological effects of AMPK activation and inhibition, mechanism, overview
-
additional information
-
a significant reduction in AMPK activation and downstream acetyl-CoA carboxylase activation in response to viral Tat protein treatment. Knockdown of SIRT1 by siRNA potentiates Tat-mediated reduction in AMPK activation and downstream acetyl-CoA carboxylase activation. Knockdown of AMPK by siRNA potentiates Tat-induced HIV-1 transactivation
-
additional information
-
overexpression of reactive oxygen species scavenger catalase prevents hypoxia-induced AMPK activation
-
additional information
-
protein phosphatase 2A (PP2A) and protein phosphatase 2C (PP2C) inactivate the active and phosphorylated form of AMPK in cell-free assays. Dephosphorylation of AMPK by PP2Calpha is inhibited by 5'-AMP
-
additional information
-
SOCS3, an inhibitor of leptin-STAT3 signalling, inhibits leptin activation of AMPK in primary myotubes
-
additional information
-
when glycogen becomes depleted, the glycogen-bound pool of AMPK becomes inhibited due to binding to alpha1-6-linked branch points exposed by the action of phosphorylase and/or debranching enzyme
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(+)-simvastatin
-
LKB1 is required for statin-dependent AMPK activation. Transfection of LKB1-expressing plasmid is required for statin-induced AMPK activation in A-549 and HeLa S3 cell lines deficient in endogenous LKB1
1-methyl-4-phenylpyridinium
-
activates AMPK in SH-SY5Y cells. Increases phosphorylation level at Thr172 in the active site of AMPKalpha. AMPK is activated during the progression of cell death mediated by 1-methyl-4-pyridinium
2-deoxyglucose
-
blocks glucose utilization and increases the intracellular AMP concentration, activation is suppressed by compound C
24-hydroxyursolic acid
-
from the leaves of Diospyros kaki, strongly activates AMPK, inhibits cell proliferation
5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside
-
i.e. AICAR, the pharmacological compound transported into cells by the adenosine transporter, and then metabolized by the enzyme adenosine kinase into 5-aminoimidazole-4-carboxamide 1-b-D-ribofuranosyl monophosphate, ZMP, an AMP analogue, which then functions like endogenous AMP by binding to the Bateman domains of AMPK and promoting allosteric activation of the kinase, AICAR does not alter endogenous levels of AMP or ATP, ZMP might prevent the dephosphorylation of AMPK by inhibition of AMP-sensitive phosphatases
A-769662
-
small molecule direct activator of AMPK, increases glucose uptake in both L6 myotubes and primary myotubes
A769662
A769662 selectively activates beta1-containing AMPK isoforms
Ca2+/calmodulin-dependent protein kinase kinase
-
i.e. CaMKKalpha/beta, increases AMPK activity regulating AMPK in a Ca2+/calmodulin-dependent, AMP-independent manner, overview
-
dinitrophenol
-
a cellular metabolic poison that activates AMPK in numerous cell types, including skeletal muscle, mechanism, overview
GINST
-
a hydrolyzed ginseng extract, phosphorylation of AMPKalpha increases 2.5fold by GINST after 360 min of treatment
-
glucocorticoid
-
treatment inhibits AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus, similar to activity in vitro in the primary adipose and hypothalamic cells
-
hydrogen peroxide
-
sublethal oxidative stress inhibits retinal pigment epithelium cell phagocytosis and activates AMPK. 0.5 mM hydrogen peroxide dramatically activates AMPKalpha, reaches the peak within 15 min, and declines 1 h later. Thr172 phosphorylation of catalytic subunit AMPKalpha is required for AMPKalpha activation
IFNgamma
-
activates AMPK by phosphorylation of Thr172, independent of intracellular energy (ATP) levels. Phosphatidylinositol 3'-kinase inhibition by LY294002 partially prevents IFNgamma-induced activation of AMPK
-
interleukin-6
-
activates AMPK in skeletal muscle by increasing the phosphorylation of Thr172 of AMPK
leptin
-
the classical adipokine, released from adipocytes, stimulates the alpha2 isoform of AMPK and hence fatty acid oxidation in skeletal muscle
-
O2
-
hypoxia leads to time-dependent AMPK activation in ATII cells. Maximal activation of AMPK after 10 min of 1.5% O2 exposure, whereas 3% O2 activates AMPK in a similar but slower manner. AMPK levels return to the baseline after 30 min of hypoxia exposure. Hypoxia-generated mitochondrial reactive oxygen species leads to the activation of the AMPK alpha1 isoform at Thr172. Hypoxia fails to activate AMPK in mitochondrion-deficient rho0-A549 cells
pioglitazone
-
i.e. 5-((4-(2-(5-ethyl-2-pyridinyl)ethoxy)-phenyl)methyl)-(+)-2,4-thiazolidinedione, a drug that is used to treat type 2 diabetes, a thiazolidinedione, reduces blood glucose levels in humans via activation of AMPK in skeletal muscle
PKC-zeta
-
is required for statin-induced LKB1 nucleus export and AMPK activation in HUVEC cells
-
puerarin
-
stimulates AMPK, puerarin down-regulated MDR1 expression via nuclear factor kappa-B and cAMP-responsive element transcriptional activity-dependent up-regulation of AMPK in MCF-7/adr cells
Reductase kinase kinase
-
activation, i.e. EC 2.7.1.110, in the presence of MgATP2-
-
resveratrol
-
reverses Tat-mediated reduction in AMPK activation and downstream acetyl-CoA carboxylase activation, inhibits Tat-induced HIV-1 transactivation
rotenone
-
a cellular metabolic poison that activates AMPK in numerous cell types, including skeletal muscle, mechanism, overview
vascular endothelial growth factor
-
activates AMPK in endothelial progenitor cells by phosphorylation at Ser172
-
AMP
phosphorylation of the activation-loop threonine (Thr172 of alpha2) or allosteric modulation by AMP binding is essential for AMPK activation
5'-AMP
-
the gamma subunit of AMPK contains adenine nucleotide binding sites that facilitate the direct interaction of AMP with the AMPK heterotrimer. AMP regulates the activity of AMPK via the inhibition of AMPK dephosphorylation by protein phosphatases
5'-AMP
-
up to 10fold activation, AMP also promotes net phosphorylation at a critical threonine residue Thr172 within the kinase domain that can generate a further 100fold activation, the combined effect being 1000fold
5-aminoimidazole-4-carboxamide ribonucleoside
-
AICAR, AMPK activator, inhibits Tat-induced HIV-1 transactivation
5-aminoimidazole-4-carboxamide ribonucleoside
-
AICAR, has a proapoptotic effect in neuroblastoma cells. AICAR does not significantly change AMPK activity after prolonged exposure (48 h), when its apoptotic effect becomes evident
5-aminoimidazole-4-carboxamide ribonucleotide
Q13131; Q9Y478; P54619
i.e. AICAR, activation of AMPK in isolated perfused proximal renal tubules by AICAR
5-aminoimidazole-4-carboxamide riboside
-
AICAR, activates AMPK, whereby increasing the rate of fatty acid oxidation in isolated human muscle strips and cultured human skeletal muscle cells. In isolated human muscle strips, AICAR induces glucose uptake, that is associated with increased translocation of the glucose transporter, GLUT4, to the plasma membrane
5-aminoimidazole-4-carboxamide riboside
-
AICAR, its activation of AMPK is abolished by preincubation with dipyridamole or 5-iodotubercidin
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
-
AICAR, increase in cytosolic Ca2+ activity by Ca2+ ionophore ionomycin triggeres eryptosis, an effect blunted by the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside at 1 mM
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
-
AICAR, increases AMPK activity
5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside
-
i.e. AICAR
5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside
-
i.e. AICAR, a potent agonist of AMPK, activates AMPK activation by p38 MAPK, AICAR must be phosphorylated itself to ZMP by adenosine kinases in order to activate AMPK
5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside
-
i.e. AICAR, activates AMPK and increases PGC-1alpha expression
5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside
-
i.e. AICAR, an AMP-activated protein kinase specific activator
5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside
-
i.e. AICAR, decreases class III PI3-kinase binding to beclin-1, and this effect counteracts and reverses the known positive effect of AMPK activity on autophagy, and AICAR inhibits the proteasomal degradation of proteins in lysosomes by an AMPK-dependent mechanism, but inhibits autophagy by an AMPK-independent mechanism
5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside
-
i.e. AICAR, the activation of AMPK negatively modulates the activated phenotype of hepatic stellate cells, AMPKactivation does not reduce PDGF-dependent activation of extracellular signal-regulated kinase, ERK, or Akt, but blocks in cell cycle progression, physiological effects of AMPK activation and inhibition, mechanism, overview
AMP
P54646; O43741; Q9UGI9
an allosteric activator for AMPK heterotrimeric complex (alpha2beta2gamma3)
AMP
the alpha2-subunit-containing enzyme complexes are more readily activated by AMP than alpha1-complexes
metformin
-
increases the activating phosphorylation of the enzyme at Thr172 of the alpha-subunit by 3.6fold
metformin
-
i.e. N,N-dimethylimidodicarbonimidic diamide, one of the most commonly prescribed drugs for the treatment of type 2 diabetes, increases the activity of AMPK in skeletal muscle, mechanism, loss of TAK1 protein prevents the metformin-induced activation of AMPK, overview
rosiglitazone
-
i.e. 5-((4-(2-(methyl-2-pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazol-idinedione, a drug that is used to treat type 2 diabetes, a thiazolidinedione, reduces blood glucose levels in humans via activation of AMPK in skeletal muscle
rosiglitazone
-
stimulates an increase in the ADP/ATP ratio and AMPK activity essentially involving LKB1 and leading to activation of nitric oxide synthesis in human aortic endothelial cells, the stimulation of AMPK and NO synthesis by rosiglitazone is unaffected by the peroxisome proliferator-activated receptor-gamma inhibitor GW9662 or by STO-609, overview
additional information
the enzyme is activated under circumstances with an increased cellular AMP:ATP ratio, such as metabolic stresses that inhibit ATP production (hypoxia, glucose deprivation, metabolic inhibitors etc.) and those that stimulate ATP consumption (exercise, cell growth and division etc.). Activation-loop conformation, overview
-
additional information
-
activating phosphorylation of AMPK at Thr172 of the alpha-subunit, e.g. by CaMKKbeta or LBK1, dephosphorylation by phosphatase PP2C
-
additional information
-
activation of AMPK requires phosphorylation at Thr172 by an AMPK kinases, e.g. LKB1 and Ca2+/calmodulin-dependent kinase kinase, CaMKK
-
additional information
-
AMPKalpha needs to be activated by phosphorylation on Thr172
-
additional information
-
phosphorylation of AMPK at Thr172 of the alpha-subunit activates the enzyme
-
additional information
-
the enzyme is activated by phosphorylation at Thr172 in the alpha subunit activation T-loop
-
additional information
-
UV and H2O2 induce AMPK activation through Thr172 phosphorylation, UV and H2O2 also phosphorylate LKB1, an upstream signal of AMPK, in an epidermal growth factor receptor-dependent manner, overview. SB203580, a p38 inhibitor, does not affect AMPK activation
-
additional information
-
activation of the alpha2 isoform of AMPK in response to exercise in human muscle, is much greater in the glycogen-depleted state. In humans with McArdle's disease (glycogen storage disease V), the activation of AMPK-alpha2 in response to a moderate level of exercise (which is all these subjects can tolerate) is significantly higher than in the controls
-
additional information
-
in healthy humans, an acute bout of exercise activates AMPK in an isoform and intensity-dependent manner
-
additional information
-
LKB1, a serine-threonine kinase of 433 amino acids, which contains both a kinase domain and a nuclear localization signal in its N-terminal region, phosphorylates the T-loop of AMPK
-
additional information
all three nucleotides AMP, ADP and ATP can bind to sites 1 and 3 with similar affinities. Phosphorylation of Thr172/Thr174 of the alpha subunit activates the enzyme isozymes
-
additional information
Q13131; Q9Y478; P54619
ischemia stimulates the AMP-activated protein kinase (AMPK)
-
additional information
P54646; O43741; Q9UGI9
small molecule activator thienopyridone A-769662 has no ativating effect on AMPK heterotrimeric complex (alpha2beta2gamma3)
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
theMichaelis-Menten enzyme kinetics and allosteric modulation of six recombinant AMPK isoforms, alpha1beta1gamma1, alpha1beta2gamma1, alpha1beta2gamma3, alpha2beta1gamma1, alpha2beta2gamma,1 and alpha2beta2gamma3 using known activators, A769662 and AMP. The alpha1-containing complexes exhibit higher specific activities and lower Km values for peptide substrate biotin-GGHMRSAMSGLHLVKRR-NH2 (SAMS) compared with alpha2-complexes. Binding affinities of AMP, ADP and ATP using surface plasmon resonance techniques, all three nucleotides AMP, ADP and ATP can bind to sites 1 and 3 with similar affinities, allosteric regulation
-
0.02667
biotin-GGHMRSAMSGLHLVKRR-NH2
pH 7.5, 30°C, enzyme construct alpha1beta1gamma1
0.03207
biotin-GGHMRSAMSGLHLVKRR-NH2
pH 7.5, 30°C, enzyme construct alpha1beta1gamma1
0.03731
biotin-GGHMRSAMSGLHLVKRR-NH2
pH 7.5, 30°C, enzyme construct alpha1beta1gamma1
0.08003
biotin-GGHMRSAMSGLHLVKRR-NH2
pH 7.5, 30°C, enzyme construct alpha1beta1gamma1
0.1076
biotin-GGHMRSAMSGLHLVKRR-NH2
pH 7.5, 30°C, enzyme construct alpha1beta1gamma1
0.1214
biotin-GGHMRSAMSGLHLVKRR-NH2
pH 7.5, 30°C, enzyme construct alpha1beta1gamma1
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000111
(Z)-2-(3-((4-((2-(diethylamino)ethyl)carbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)ethyl acetate
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
-
0.000108
(Z)-5-((5-(2-acetamidoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.000101
(Z)-5-((5-(2-azidoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000324
(Z)-5-((5-(2-cyanoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000607
(Z)-5-((5-(3-amino-3-oxopropyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000162
(Z)-5-((5-cyano-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
-
0.0000825
(Z)-5-((6-bromo-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000651
(Z)-5-((6-chloro-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000836
(Z)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-5-((2-oxo-5-(ureidomethyl)indolin-3-ylidene)methyl)-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
-
0.0000885
(Z)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-5-((2-oxoindolin-3-ylidene)methyl)-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.000154
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-(dimethylamino)ethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000205
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-hydroxyethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000966
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-methoxyethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
-
0.0000494
(Z)-N-(2-(diethylamino)ethyl)-5-((6-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000504
(Z)-N-(2-(dimethylamino)ethyl)-5-((5-floro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000614
(Z)-N-(2-(ethylamino)ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.000141
(Z)-N-(2-aminoethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene) methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000386
(Z)-N-(3-(diethylamino)propyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.0000748
(Z)-N-(3-(dimethylamino)propyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.00617
N-[2-(diethylamino)ethyl]-5-[(Z)-(6-fluoro-2-oxo-2,3-dihydro-1H-inden-1-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha2, at pH 7.5 and 25°C
0.000418
(Z)-2-(3-((4-((2-(diethylamino)ethyl)carbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)ethyl acetate
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
-
0.000184
(Z)-5-((5-(2-acetamidoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000139
(Z)-5-((5-(2-azidoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000164
(Z)-5-((5-(2-cyanoethyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000107
(Z)-5-((5-(3-amino-3-oxopropyl)-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000093
(Z)-5-((5-cyano-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
-
0.000208
(Z)-5-((6-bromo-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000217
(Z)-5-((6-chloro-2-oxoindolin-3-ylidene)methyl)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000205
(Z)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-5-((2-oxo-5-(ureidomethyl)indolin-3-ylidene)methyl)-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
-
0.000246
(Z)-N-(2-(diethylamino)ethyl)-2,4-dimethyl-5-((2-oxoindolin-3-ylidene)methyl)-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.0021
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-(dimethylamino)ethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000173
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-hydroxyethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000296
(Z)-N-(2-(diethylamino)ethyl)-5-((5-(2-methoxyethyl)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
-
0.000348
(Z)-N-(2-(diethylamino)ethyl)-5-((6-ethyl-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.00024
(Z)-N-(2-(diethylamino)ethyl)-5-((6-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000136
(Z)-N-(2-(dimethylamino)ethyl)-5-((5-floro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.00018
(Z)-N-(2-(ethylamino)ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000393
(Z)-N-(2-aminoethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene) methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000152
(Z)-N-(3-(diethylamino)propyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000221
(Z)-N-(3-(dimethylamino)propyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
0.000158
N-[2-(diethylamino)ethyl]-5-[(Z)-(6-fluoro-2-oxo-2,3-dihydro-1H-inden-1-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
Homo sapiens
subunit AMPKalpha1, at pH 7.5 and 25°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
HeLa cells stably expressing wild type LKB1 or a kinase-inactive mutant LKB1
-
different isozymes in muscles by different combinations of subunits, i.e. alpha1/beta2/gamma1, alpha2/beta2/gamma1, and alpha2/beta2/gamma3, overview
P54646; O43741; Q9UGI9
in human skeletal muscle, the alpha2beta2gamma3 complexes constitutes the majority of AMPK heterotrimers
additional information
the alpha2 isoform is abundant in cardiac and skeletal muscle
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
at prophase, P-AMPKalpha-Thr172 associates with the two asters of microtubules that begin to nucleate from mature centrosomes. Overlapping localization of P-AMPKalpha-Thr172 with the mitotic centrosomal Aurora-A kinase on the microtubules near the spindle poles in metaphase and in early anaphase. Localization of P-AMPKalpha-Thr172 at the central spindle and midbody persists during the furrowing process and at the completion of telophase. P-AMPKalpha-Thr172 localization at centrosomes requires dynamic microtubules
additional information
-
differential localization patterns of AMPKalpha 1 and AMPKalpha2
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a sensor to maintain energy balance at both the cellular and the whole-body levels. The enzyme is activated under circumstances with an increased cellular AMP:ATP ratio, such as metabolic stresses that inhibit ATP production (hypoxia, glucose deprivation, metabolic inhibitors etc.) and those that stimulate ATP consumption (exercise, cell growth and division etc.)
malfunction
metabolism
physiological function
additional information
malfunction
-
AMPK gamma2 mutations are associated with hypertrophic cardiomyopathy
malfunction
-
mutations in the gamma2 and gamma3 subunits result in glycogen storage disease. Ten point mutations in gamma2 are associated with a glycogen storage cardiomyopathy and ventricular pre-excitation
malfunction
stabilization of MAPO1 occurs in AMPKalpha-knockdown cells even without N-methyl-N-nitrosourea treatment. Knockdown of the Flcn and Ampkalpha genes by specific siRNAs significantly suppresses an apoptotic response to N-methyl-N-nitrosourea
malfunction
the absence of functional AMPK may consequently cause a failure of distinct signaling pathways in red bood cells
malfunction
-
enzyme ablation increases Zika virus replication and reduces innate antiviral responses
metabolism
-
is a key regulator of cellular and whole-body energy homeostasis that co-ordinates metabolic pathways in order to balance nutrient supply with energy demand
metabolism
-
plays an important role in the regulation of both lipid and glucose metabolism. Direct link between AMPK activation and fatty acid metabolism. Has the potential of ameliorating insulin resistance and improving glucose homeostasis. A gain-of-function mutation in the gene encoding AMPK gamma3-subunit is reported to confer beneficial effects on muscle fuel metabolism
physiological function
-
activation of AMPK alpha is necessary for hypoxia-induced AMPK-PKCzeta binding in alveolar epithelial cells. Overexpression of a dominant-negative AMPK alpha subunit construct prevents hypoxia-induced endocytosis of Na,K-ATPase, hypoxia-induced PKCzeta translocation to the plasma membrane and phosphorylation at Thr410
physiological function
-
activation of AMPK may prevent neuronal cell death and play a role as a survival factor in Parkinson's disease. Overexpression of AMPK increases cell viability after exposure to 1-methyl-4-pyridinium in SH-SY5Y cells
physiological function
-
AMPK activation during oxidative stress may switch retinal pigment epithelium cells to a self-protected status. Alpha2 but not alpha1 AMPK is involved in retinal pigment epithelium cell phagocytosis and activation of alpha2 AMPK contributes to the inhibition of retinal pigment epithelium cell phagocytosis by oxidative stress
physiological function
-
AMPK activation inhibits TNFa-stimulated leukocyte adhesion to aortic endothelial cells and ICAM-1 mediated migration of lymphocytes across primary microvascular endothelial cells
physiological function
-
AMPK is required for proper cell division and faithful chromosomal segregation during mitosis. Active form of the alpha-catalytic AMPK subunit (P-AMPKalpha-Thr172), but not its total form (AMPKalpha), transiently associates with several mitotic structures including centrosomes, spindle poles, the central spindle midzone and the midbody throughout all of the mitotic stages and cytokinesis in human cancer-derived epithelial cells
physiological function
-
AMPK may play an important role in protecting endothelial cells against adverse effects of sustained hyperglycaemia, such as alterations in fatty acid metabolism, impaired Akt activation by insulin, increased caspase 3 activity and apoptosis. It may modulate endothelial cell energy supply. The AMPK-acetyl CoA carboxylase-malonyl CoA-carnitine palmitoyl-transferase 1 mechanism for regulating long-chain fatty acid oxidation, similar to that of muscle, operates in the endothelial cell and is regulated by AMPK under physiological conditions. One way to deal with endothelial lipotoxicity is to promote free fatty acid oxidation and ameliorate lipid accumulation in endothelial cells, which can be achieved by activating endothelial AMPK. AMPK inhibits fatty acid-induced increases in NF-kappaB transactivation in cultured human umbilical vein endothelial cells
physiological function
-
role for AMPK, in concert with other signals induced by IFNgamma, in mediating reduced epithelial barrier function in a cell model of chronic intestinal inflammation
physiological function
-
role of AMPK is that it monitors cellular energy status by sensing the relative cellular concentrations of AMP and ATP. The beta-subunits of AMPK contain a glycogen-binding domain, which is a regulatory domain that allows AMPK to act as a sensor of the status of cellular reserves of energy in the form of glycogen. The pool of AMPK that is bound to the glycogen particle is in an active state when glycogen particles are fully synthesized, causing phosphorylation of glycogen synthase at site 2 and providing a feedback inhibition of further extension of the outer chains of glycogen
physiological function
AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that is essential in regulating energy metabolism in all eukaryotic cells
physiological function
AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that serves as a pleotropic regulator of whole body energy homoeostasis. The enzyme is allosterically regulated, kinetic analysis, overview. Binding of activator AMP to the gamma-subunit allows a small regulatory segment of the alpha-subunit (alpha2 residues 365-371) called the alpha-hook or alpha-RIM2 to directly interact with bound AMP and create an allosteric conformational change at the catalytic active site. As a consequence, the phosphorylated alpha-Thr172/174 can be protected from dephosphorylation by phosphatases and sustain its kinase activity for an extended period
physiological function
P54646; O43741; Q9UGI9
AMP-activated protein kinase (AMPK) is an energy-sensing serine/threonine protein kinase that plays a central role in whole-body energy homeostasis. The muscle-specific AMPK heterotrimeric complex (alpha2beta2gamma3) is involved in glucose and fat metabolism in skeletal muscle
physiological function
AMPK is a cellular energy sensor that negatively regulates cell growth and proliferation. MAPO1, identified as a component involved in the induction of apoptosis, is stabilized by interaction with AMP-activated protein kinase (AMPK) and folliculin (FLCN). AMPK is activated during the process of O6-methylguanine-induced apoptosis and this activation is dependent on MAPO1 and folliculin. It is likely that the kinase activity of AMPK is involved in the degradation of MAPO1
physiological function
AMPK is a metabolic stress-sensing kinase with important functions for red blood cell survival. Identification of putative AMPK targets in hemoglobin-depleted lysates of erythrocytes, including metabolic enzymes, cytoskeletal proteins and enzymes involved in the oxidative stress response, cloning and recombinant expression. AMPK aids the function of red blood cells
physiological function
Q13131; Q9Y478; P54619
ischemia stimulates the AMP-activated protein kinase (AMPK), a serine/threonine kinase, sensing energy depletion and stimulating several cellular mechanisms to enhance energy production and to limit energy utilization. AMPK downregulates the epithelial Na+ channel ENaC mediated by the ubiquitin ligase Nedd4-2. AMPK regulates the heterotetrameric K+-channel KCNQ1/KCNE1. Wild-type and constitutively active AMPK significantly reduce KCNQ1/KCNE1-mediated currents and reduce KCNQ1 abundance in the cell membrane of transfected Xenopus laevis oocytes, overview. AMPK decreased the KCNQ1 protein abundance in the cell membrane via ubiquitin ligase Nedd4-2
physiological function
-
enzyme phosphorylation inhibits the activation of human hepatic stellate cell line LX-2. Enzyme activation in LX-2 cells inhibits autophagosome formation. Enzyme activation inhibits transforming growth factor-beta-induced intracellular lipid droplet depletion, which relies on increased autophagic flux, and finally inhibits transforming growth factor-beta-induced hepatic stellate cell activation
physiological function
-
the enzyme has an antiviral effect on Zika virus replication. The anti-Zika virus effect of enzyme signaling in endothelial cells is mediated by reduction of viral-induced glycolysis and enhanced innate antiviral responses
additional information
the AMPK alpha2 kinase domain exhibits a typical bilobal kinase fold and exists as a monomer in the crystal. Like the wild-type apo form, the T172D mutant apo form adopts the autoinhibited structure of the DFG-out conformation, with the Phe residue of the DFG motif anchored within the putative ATP-binding pocket
additional information
alpha1-subunit containing AMPK isoforms possess higher basal activity and are less sensitive to desphosphorylation by phosphatases compared with alpha2-subunit containing heterotrimers. The alpha2-subunit-containing complexes are more readily activated by AMP than alpha1-complexes. Enzymatic activity, phosphatase sensitivity and kinetics of alpha1- and alpha2-containing AMPK isoforms, differential effect of activators, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). AAPK2_HUMAN
552
0
62320
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
155000
P54646; O43741; Q9UGI9
recombinant His-tagged full-length alpha2beta2gamma3 heterotrimeric AMPK complex, gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
heterotrimer
trimer
additional information
?
x * 37953, recombinant phosphorylated AMPK alpha1 subunit, mass spectrometry
heterotrimer
P54646; O43741; Q9UGI9
1 * 64000, recombinant His-tagged alpha2 subunit, + 1 * 54000, recombinant His-tagged beta2 subunit, + 1* 33000, recombinant His-tagged gamma3 subunit, SDS-PAGE
heterotrimer
AMPK exists as a heterotrimeric complex, composed of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma), each present as multiple isoforms
heterotrimer
enzyme AMPK is a heterotrimeric protein complex composed of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma)
heterotrimer
enzyme AMPK is composed of AMPKalpha, beta and gamma subunits
trimer
-
alphabetagamma heterotrimer composed of different alpha, beta, and gamma subunit variants
trimer
-
AMPK exists as heterotrimeric complexes comprising catalytic alpha subunits and regulatory beta and gamma subunits, with multiple genes encoding each subunit in mammals, alpha1, alpha2, beta1, beta2, gamma1, gamma2, gamma3
trimer
-
different heterotrimers resulting in different isozymes, the alphabetagamma composition can be formed by two different alpha subunit variants, two different beta and three different gamma subunits, overview
trimer
-
heterotrimeric AMPK consists of a catalytic alpha subunit, and regulatory beta and gamma subunits
trimer
-
in human skeletal muscle, the alpha2beta2gamma3 complexes constitute the majority of AMPK heterotrimers
additional information
the AMPK alpha2 kinase domain exhibits a typical bilobal kinase fold and exists as a monomer in the crystal. Like the wild-type apo form, the T172D mutant apo form adopts the autoinhibited structure of the DFG-out conformation, with the Phe residue of the DFG motif anchored within the putative ATP-binding pocket. Three-dimensional structure analysis, overview. The kinase domain structures display the typical bilobal protein-kinase fold
additional information
-
heterotrimeric serine/threonine kinase consists of a catalytic alpha-subunit and 2 regulatory subunits beta and gamma, each subunit exists as multiple isoforms, alpha1, alpha2, beta1, beta2, gamma1, gamma2 and gamma3, giving 12 different possible combinantions of holoenzyme with different tissue distribution and subcellular localization
additional information
-
AMPK consists of a catalytic alpha subunit and two non-catalytic subunits,beta and gamma, each with multiple isoforms that form active 1:1:1 heterotrimers
additional information
-
several isoforms for each of the three AMPK subunits, including alpha1, alpha2, beta1, beta2, gamma1, gamma2, and gamma3, AMPKalpha subunit possesses a highly conserved, N-terminal catalytic domain that contains the activating phosphorylation site Thr172, an autoinhibitory domain, and a C-terminus that contains the domains required for binding with the beta and gamma subunits, subunit structures, overview
additional information
P54646; O43741; Q9UGI9
AMPK is a heterotrimeric enzyme with a catalytic (alpha) subunit and two regulatory (beta and gamma) subunits
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
enzyme activation by phosphorylation on Thr172, LKB1, Ca2+/calmodulin-dependent protein kinase kinase, ATM and TAK1 are AMPK kinases
phosphoprotein
phosphoprotein
-
the enzyme is phosphorylated at Thr172 of its alpha-subunit, phosphorylation activates the enzyme, metformin increases the enzyme phosphorylation
phosphoprotein
-
8-chloro-cAMP and no 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside induce AMPK phosphorylation
phosphoprotein
-
activating phosphorylation of AMPK at Thr172 of the alpha-subunit, e.g. by CaMKKbeta or LBK1, dephosphorylation by phosphatase PP2C
phosphoprotein
-
activation of AMPK requires phosphorylation at Thr172 by an AMPK kinases, e.g. LKB1 and Ca2+/calmodulin-dependent kinase kinase, CaMKK
phosphoprotein
-
phosphorylation at alpha1-Thr172 by CaMKKbeta, and at alpha1-Ser485, beta1-Ser108, and beta1-Ser182 in Sf21 cells, determination of phosphorylation sites by mass spectrometry, phosphorylation also by LKB1, overview
phosphoprotein
-
phosphorylation of AMPK at Thr172 of the alpha-subunit inducd by 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside
phosphoprotein
-
the enzyme is activated by phosphorylation at Thr172 in the alpha subunit activation T-loop
phosphoprotein
-
UV and H2O2 induce AMPK activation through Thr172 phosphorylation
phosphoprotein
activation of the enzyme by phosphorylation of Thr172 of the alpha subunit. Thr172 is the only site phosphorylated by its upstream kinase, liver kinase B1, and the phosphorylation dramatically increases the kinase activity of the catalytic domain/alpha-subunit. Phosphorylation of AMPK alpha1 on Thr172 by LKB1/Ste20-related adaptor (STRAD)/mouse protein 25(MO25) complex. Top-down mass spectrometric analysis, overview. Ser18 and Ser22 in the His-tag region as well as Thr196 (equivalent to Thr172 in the unmodified enzyme) in the sequence of the AMPK catalytic domain are the three phosphorylation sites
phosphoprotein
autophosphorylation of 5'-AMP-activated protein kinase catalytic subunit alpha-1
phosphoprotein
phosphorylation of Thr172/Thr174 of the alpha subunit activates the enzyme isozymes
phosphoprotein
-
the enzyme can be activated by direct phosphorylation by the upstream kinase liver kinase B1 at the site of Thr172 on the alpha-subunit, or through indirect allosteric changes of the gamma-subunit, thereby regulating the phosphorylation state of the alpha-subunit
phosphoprotein
-
Zika virus infection results in a decrease in AMPKalpha phosphorylation at Thr172
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified AMPK alpha2 subunit in apoform and in complex with compound C inhibitor, for the apoform: hanging-drop vapour diffusion method, mixing of 2.8 mg/ml protein in 20 mM Tris-HCl, pH 8.5, 0.3 M NaCl, 10% glycerol, 2 mM DTT, 5 mM MgCl2, and 5 mM AMPPNP, with reservoir solution consisting of 0.1 M Tris-HCl pH 8.9, 15% 2-propanol, 0.1 M ammonium sulfate, and 16% PEG 4000, for the complexed form: sitting-drop vapour-diffusion method, mixing of 2.8 mg/mlprotien in 20 mM Tris-HCl, pH 8.5, 0.3 M NaCl, 10% glycerol, 2 mM DTT, 5 mM MgCl2, and 0.5 mM compound C, with reservoir solution consisting of 0.1 M Bis-Tris, pH 6.5, 1.5 M ammonium sulfate, and 0.1 M NaCl, 20°C, X-ray diffraction structure determination and analysis at 2.08-3.0 A resolution, molecular replacement, modelling, overview
crystal structure of the inactive, apo-form of AMPK alpha2 subunit N-terminal kinase catalytic domain (KCD, residues 10-278 inclusive), shows that it adopts a canonical bilobal structure with the active site forming a cleft between the two lobes. The small N-terminal lobe (residues 1-97) is composed of a five-stranded beta-sheet (beta1-beta5), with an alpha-helix (termed the C-helix) positioned between strands beta3 and beta4 and lying to one side of the beta sheet. Glu-64 within the C-helix is important for aligning the phosphates of ATP in the correct orientation for catalysis. A Gly-X-Gly-X-X-Gly P-loop motif connecting strands beta1 and beta2 is evident in the structure. This interacts with the beta phosphate group of ATP when the active site is occupied. The larger C-terminal lobe is predominantly (63%) alpha-helical (alphaD-alphaI) and contains determinants and structural features that dictate protein substrate binding. The two lobes are connected via a short, flexible hinge region that allows rotation of the two lobes relative to each other
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
T172D
site-directed mutagenesis of AMPK subunit alpha2, a phosphorylated-state mimic mutant. The activity of the T172D mutant kinase domain with and without AMPK kinase is about 40fold higher than that of the wild-type kinase domain treated with protein phosphatase 2A. The apo-form structure of the T172D mutant is essentially identical to that published for the wild type
K45R
R225W
-
naturally occuring mutation of the gamma3 subunit, which leads to a 2fold increased AMPK activity, a 90% increase in skeletal muscle glycogen content and a 30% decrease in triglycerides
R70Q
T172D
additional information
K45R
-
site-directed mutagenesis, a dominant-negative mutant, expression leads to accumulation of lipids in cells
K45R
Q13131; Q9Y478; P54619
site-directed mutagenesis, a kinase dead mutant AMPK, the mutant is ineffective in inhibiting heterotetrameric K+-channel KCNQ1/KCNE1
R70Q
-
site-directed mutagenesis, marked increase in activity, largely AMP-independent
R70Q
Q13131; Q9Y478; P54619
site-directed mutagenesis, the constitutively active mutant is more effective in inhibiting heterotetrameric K+-channel KCNQ1/KCNE1 than the wild-type enzyme
T172D
-
site-directed mutagenesis, constitutively active mutant of AMPK, insensitive to metformin
additional information
-
a dominant negative AMP-activated protein kinase mutant abrogates rosiglitazone-stimulated Ser1177 phosphorylation and NO production in endothelial cells
additional information
-
activating mutations in AMPK can cause heart disease, detailed overview
additional information
-
AMPK silencing increases PDGF-induced proliferation of hepatic stellate cells
additional information
-
enzyme inhibition by expression of a dominant negative expression vector with kinase-dead form of AMPKalpha2
additional information
-
overexpression of the kinase-negative AMPK inhibits enzyme activation by 2-deoxyglucose
additional information
C-terminal truncation of AMPKalpha at residue 312 yields a protein that is active upon phosphorylation of Thr172 in the absence of beta and gamma subunits, which is refered to as the AMPK catalytic domain and commonly used to substitute for AMPK heterotrimeric complex in in vitro kinase assays
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged AMPK alpha2 mutant by affinity chromatography and gel filtration
different recombinant His6-tagged subunit constructs from Escherichia coli strain BL21-CodonPlusTM (DE3)-RIPL by nickel affinity chromatography and dialysis
functional full-length recombinant alpha2beta2gamma3 heterotrimeric complex of human AMP-activated protein kinase from Escherichia coli strain CodonPlus(DE3)-RIPL by nickel affinity chromatography, dialysis and two steps of gel filtration
P54646; O43741; Q9UGI9
recombinant GST-tagged isozyme AMPK alpha1beta1gamma1 from Spodoptera frugiperda Sf21 cells by glutathione affinity and anion exchange chromatography, and gel filtration
-
recombinant His-tagged isozymes alpha1 and alpha2 from Escherichia coli by nickel affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene PRKAA2, recombinant expression of kinase domain (residues 6-279) of the AMPK alpha2 mutant with an N-terminal His-tag and a tobacco etch virus (TEV) protease cleavage site via Escherichia coli cell-free system using the dialysis method
AMPK alpha subunits (alpha1 and alpha2) tagged with green fluorescent protein at the N-terminus and co-expressed with beta and gamma subunits in CCL13 cells
-
ATII cells infected with a hemagglutinin-tagged adenovirus carrying the dominant-negative mutant K45R of the AMPK alpha1 subunit or with an adenovirus expressing a constitutively active AMPK alpha variant or with an adenovirus expressing a constitutively active AMPK alpha variant in which Thr172 is replaced with aspartate in the truncated AMPK alpha subunit, comprising residues 1 to 312. A549 cells transfected with AMPK alpha1
-
expression of a dominant negative kinase-dead form of AMPKalpha2 in HeLa cells
-
expression of GST-fused constitutively active form of AMPK alpha1, residues 1-312, and of the kinase-dead mutant AMPK in HEK-193 cells
-
expression of His6-tagged beta1(186-270)gamma1 complex and of GST-tagged isozyme AMPK alpha1beta1gamma1 in Spodoptera frugiperda Sf21 cells
-
expression of mutant enzymes in Escherichia coli and, via adenovirus transfection, in Hep-G2 cells
-
expression of the AMPKalpha1 dominant negative mutant D175A in fibroblasts as GFP-tagged enzyme using an adenoviral transfection system
-
functional His-tagged full-length recombinant alpha2beta2gamma3 heterotrimeric complex of human AMP-activated protein kinase is recombinantly expressed in Escherichia coli strain CodonPlus(DE3)-RIPL. All three subunits of AMPK alpha2beta2gamma3 are transcribed as a single tricistronic transcript driven by the T7 RNA polymerase promoter, allowing spontaneous formation of the heterotrimeric complex in the bacterial cytosol
P54646; O43741; Q9UGI9
quantitative AMPK expression analysis in different tissues with or without glucocorticosteroid treatment, overview
-
recombinant coexpression of different His6-tagged subunit constructs in Escherichia coli strain BL21-CodonPlusTM (DE3)-RIPL, coexpression with biotin-ligase (BirA)
recombinant expression of His-tagged AMPK catalytic domain in Escherichia coli strain Rossetta (DE3)
transient expression of wild-type and mutant enzymes in COS-7 cells, co-expression with histone deacetylase 5
-
wild-type HA-tagged AMPKalpha1, FLAG-tagged AMPKbeta1, HA-tagged AMPKgamma1, constitutively active HA-tagged AMPKgamma1 mutant R70Q , kinase dead mutant HA-tagged AMPKalpha1 mutant K45R, and wild type HA-tagged AMPK alpha2, recombinant expression in Xenopus laevis oocytes. Coexpression with human KCNQ1/KCNE1. AMPK inhibites voltage-gated outward currents in KCNQ1/KCNE1-expressing Xenopus oocytes. Coexpression of the AMP-activated protein kinase, i.e. AMPKalpha1, AMPKbeta1, and AMPKgamma1
Q13131; Q9Y478; P54619
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
alpha1 and alpha2 AMPK siRNAs selectively suppress AMPKalpha1 and AMPKalpha2 protein, respectively. AMPKalpha1 and AMPKalpha2 proteins are reduced to 6 and 1% of respective controls. Combined treatment with both alpha1 and alpha2 AMPK siRNAs lead to 66 and 92% reduction of AMPKalpha1 and AMPKalpha2 protein, respectively
-
AMPKalpha1 repression causes a 37% compensational increase in AMPKalpha2 protein
-
siRNA knockdown of AMPK, which ameliorates the IFNgamma-induced increase in epithelial permeability and decrease in transepithelial electrical resistance
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
AMP-activated protein kinase (AMPK) is a potential target for drug design against metabolic syndrome, obesity and type 2 diabetes
drug development
medicine
drug development
-
pharmacological activators of AMPK can act as treatments for diabetes and the metabolic syndrome
drug development
-
activating AMPK may have therapeutic potential in treating dry macular degeneration
drug development
-
AMPK is a highly attractive target for the prevention and treatment of type 2 diabetes and other disorders of the metabolic syndrome, and to curb the prevalence and costs of type 2 diabetes
drug development
-
AMPK is regarded as one of the most promising targets for new drugs to treat the growing incidence of metabolic diseases such as obesity and type 2 diabetes and cardiovascular disease
drug development
-
AMPK represents an attractive therapeutic target for vascular disease treatment
drug development
-
targeting SIRT1-AMPK pathway may serve as a new target for the development of new anti HIV-1 agents
drug development
P54646; O43741; Q9UGI9
AMPK alpha2beta2gamma3 is an attractive target for drug development for diabetes and metabolic syndrome
drug development
design and development of isoform-selective AMPK activators that are likely to be useful for the treatment of cardiovascular and metabolic diseases
medicine
-
decreasing the ischaemic-induced activation of AMPK may be a therapeutic approach to treating ischaemic heart disease, AMPK may be an important pharmacological target for improving cardiac efficiency following ischaemia
medicine
-
defects or disuse of the AMPK signaling system would be predicted to result in many of the metabolic perturbations observed in type 2 diabetes mellitus
medicine
-
implication of AMPK in the pathogenesis of chronic intestinal inflammatory conditions, such as inflammatory bowel disease
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Stapleton, D.; Mitchelhill, K.I.; Gao, G.; Widmer, J.; Michell, B.J.; Teh, T.; House, C.M.; Fernandez, C.S.; Cox, T.; Witters, L.A.; Kemp, B.E.
Mammalian AMP-activated protein kinase subfamily
J. Biol. Chem.
271
611-614
1996
Homo sapiens, Rattus norvegicus, Sus scrofa
Wang, W.; Fan, J.; Yang, X.; Furer-Galban, S.; Lopez de Silanes, I.; von Kobbe, C.; Guo, J.; Georas, S.N.; Foufelle, F.; Hardie, D.G.; Carling, D.; Gorospe, M.
AMP-activated kinase regulates cytoplasmic HuR
Mol. Cell. Biol.
22
3425-3436
2002
Homo sapiens
Hopkins, T.A.; Dyck, J.R.B.; Lopaschuk, G.D.
AMP-activated protein kinase regulation of fatty acid oxidation in the ischaemic heart
Biochem. Soc. Trans.
31
207-212
2003
Homo sapiens
Wang, W.; Yang, X.; Lopez de Silanes, I.; Carling, D.; Gorospe, M.
Increased AMP:ATP ratio and AMP-activated protein kinase activity during cellular senescence linked to reduced HuR function
J. Biol. Chem.
278
27016-27023
2003
Homo sapiens
Beg, Z.H.; Stonik, J.A.; Brewer, B.
Human hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase: evidence for the regulation of enzymic activity by a bicyclic phosphorylation cascade
Biochem. Biophys. Res. Commun.
119
488-498
1984
Homo sapiens
Winder, W.W.; Hardie, D.G.
AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes
Am. J. Physiol.
277
E1-10
1999
Homo sapiens
Hamilton, S.R.; Stapleton, D.; O'Donnell, J.B.; Kung, J.T.; Dalal, S.R.; Kemp, B.E.; Witters, L.A.
An activating mutation in the g1 subunit of the AMP-activated protein kinase
FEBS Lett.
500
163-168
2001
Homo sapiens
Warden, S.M.; Richardson, C.; O'Donnell, J.Jr.; Stapleton, D.; Kemp, B.E.; Witters, L.A.
Post-translational modifications of the beta-1 subunit of AMP-activated protein kinase affect enzyme activity and cellular localization
Biochem. J.
354
275-283
2001
Homo sapiens
Morrow, V.A.; Foufelle, F.; Connell, J.M.; Petrie, J.R.; Gould, G.W.; Salt, I.P.
Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells
J. Biol. Chem.
278
31629-31639
2003
Homo sapiens
Zang, M.; Zuccollo, A.; Hou, X.; Nagata, D.; Walsh, K.; Herscovitz, H.; Brecher, P.; Ruderman, N.B.; Cohen, R.A.
AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells
J. Biol. Chem.
279
47898-47905
2004
Homo sapiens
Crawford, R.M.; Treharne, K.J.; Best, O.G.; Muimo, R.; Riemen, C.E.; Mehta, A
A novel physical and functional association between nucleoside diphosphate kinase A and AMP-activated protein kinase alpha1 in liver and lung
Biochem. J.
392
201-209
2005
Homo sapiens, Rattus norvegicus
Browne, G.J.; Finn, S.G.; Proud, C.G.
Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398
J. Biol. Chem.
279
12220-12231
2004
Homo sapiens
Li, X.; Han, Y.; Pang, W.; Li, C.; Xie, X.; Shyy, J.Y.; Zhu, Y.
AMP-activated protein kinase promotes the differentiation of endothelial progenitor cells
Arterioscler. Thromb. Vasc. Biol.
28
1789-1795
2008
Homo sapiens
Viana, R.; Aguado, C.; Esteban, I.; Moreno, D.; Viollet, B.; Knecht, E.; Sanz, P.
Role of AMP-activated protein kinase in autophagy and proteasome function
Biochem. Biophys. Res. Commun.
369
964-968
2008
Homo sapiens
Witczak, C.A.; Sharoff, C.G.; Goodyear, L.J.
AMP-activated protein kinase in skeletal muscle: from structure and localization to its role as a master regulator of cellular metabolism
Cell. Mol. Life Sci.
65
3737-3755
2008
Saccharomyces cerevisiae, Homo sapiens, Rattus norvegicus
McGee, S.L.; van Denderen, B.J.; Howlett, K.F.; Mollica, J.; Schertzer, J.D.; Kemp, B.E.; Hargreaves, M.
AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5
Diabetes
57
860-867
2008
Homo sapiens
Osler, M.E.; Zierath, J.R.
Adenosine 5-monophosphate-activated protein kinase regulation of fatty acid oxidation in skeletal muscle
Endocrinology
149
935-941
2008
Homo sapiens
Christ-Crain, M.; Kola, B.; Lolli, F.; Fekete, C.; Seboek, D.; Wittmann, G.; Feltrin, D.; Igreja, S.C.; Ajodha, S.; Harvey-White, J.; Kunos, G.; Mueller, B.; Pralong, F.; Aubert, G.; Arnaldi, G.; Giacchetti, G.; Boscaro, M.; Grossman, A.B.; Korbonits, M.
AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushings syndrome
FASEB J.
22
1672-1683
2008
Homo sapiens, Rattus norvegicus
Hardie, D.G.
Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease
FEBS Lett.
582
81-89
2008
Arabidopsis thaliana, Saccharomyces cerevisiae, Caenorhabditis elegans, Dictyostelium discoideum, Drosophila melanogaster, Giardia intestinalis, Homo sapiens, Mus musculus, Physcomitrium patens, Rattus norvegicus, Schizosaccharomyces pombe, Trypanosoma brucei
Caligiuri, A.; Bertolani, C.; Guerra, C.T.; Aleffi, S.; Galastri, S.; Trappoliere, M.; Vizzutti, F.; Gelmini, S.; Laffi, G.; Pinzani, M.; Marra, F.
Adenosine monophosphate-activated protein kinase modulates the activated phenotype of hepatic stellate cells
Hepatology
47
668-676
2008
Homo sapiens
Boyle, J.G.; Logan, P.J.; Ewart, M.; Reihill, J.A.; Ritchie, S.A.; Connell, J.M.; Cleland, S.J.; Salt, I.P.
Rosiglitazone stimulates nitric oxide synthesis in human aortic endothelial cells via AMP-activated protein kinase
J. Biol. Chem.
283
11210-11217
2008
Homo sapiens
Cao, C.; Lu, S.; Kivlin, R.; Wallin, B.; Card, E.; Bagdasarian, A.; Tamakloe, T.; Chu, W.M.; Guan, K.L.; Wan, Y.
AMP-activated protein kinase contributes to UV- and H2O2-induced apoptosis in human skin keratinocytes
J. Biol. Chem.
283
28897-28908
2008
Homo sapiens
Miyamoto, T.; Oshiro, N.; Yoshino, K.; Nakashima, A.; Eguchi, S.; Takahashi, M.; Ono, Y.; Kikkawa, U.; Yonezawa, K.
AMP-activated protein kinase phosphorylates Golgi-specific brefeldin A resistance factor 1 at Thr1337 to induce disassembly of Golgi apparatus
J. Biol. Chem.
283
4430-4438
2008
Homo sapiens
Iseli, T.J.; Oakhill, J.S.; Bailey, M.F.; Wee, S.; Walter, M.; van Denderen, B.J.; Castelli, L.A.; Katsis, F.; Witters, L.A.; Stapleton, D.; Macaulay, S.L.; Michell, B.J.; Kemp, B.E.
AMP-activated protein kinase subunit interactions: beta1:gamma1 association requires beta1 Thr-263 and Tyr-267
J. Biol. Chem.
283
4799-4807
2008
Homo sapiens, Rattus norvegicus
Han, J.H.; Ahn, Y.H.; Choi, K.Y.; Hong, S.H.
Involvement of AMP-activated protein kinase and p38 mitogen-activated protein kinase in 8-Cl-cAMP-induced growth inhibition
J. Cell. Physiol.
218
104-112
2009
Homo sapiens
Irrcher, I.; Ljubicic, V.; Kirwan, A.F.; Hood, D.A.
AMP-activated protein kinase-regulated activation of the PGC-1alpha promoter in skeletal muscle cells
PLoS ONE
3
e3614
2008
Homo sapiens
Hegarty, B.D.; Turner, N.; Cooney, G.J.; Kraegen, E.W.
Insulin resistance and fuel homeostasis: the role of AMP-activated protein kinase
Acta Physiol. (Oxf.)
196
129-145
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Oakhill, J.S.; Scott, J.W.; Kemp, B.E.
Structure and function of AMP-activated protein kinase
Acta Physiol. (Oxf.)
196
3-14
2009
Saccharomyces cerevisiae, Homo sapiens, Mus musculus, Rattus norvegicus, Schizosaccharomyces pombe, Sus scrofa
McBride, A.; Hardie, D.G.
AMP-activated protein kinase--a sensor of glycogen as well as AMP and ATP?
Acta Physiol. (Oxf.)
196
99-113
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Choi, J.S.; Park, C.; Jeong, J.W.
AMP-activated protein kinase is activated in Parkinsons disease models mediated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Biochem. Biophys. Res. Commun.
391
147-151
2010
Homo sapiens, Mus musculus
Vazquez-Martin, A.; Oliveras-Ferraros, C.; Menendez, J.A.
The active form of the metabolic sensor: AMP-activated protein kinase (AMPK) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis
Cell Cycle
8
2385-2398
2009
Homo sapiens
Zou, M.H.; Wu, Y.
AMP-activated protein kinase activation as a strategy for protecting vascular endothelial function
Clin. Exp. Pharmacol. Physiol.
35
535-545
2008
Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces sp.
Li, C.; Keaney, J.F.
AMP-activated protein kinase: a stress-responsive kinase with implications for cardiovascular disease
Curr. Opin. Pharmacol.
10
111-115
2010
Saccharomyces cerevisiae, Canis lupus familiaris, Homo sapiens, Mus musculus, Rattus norvegicus
Foeller, M.; Sopjani, M.; Koka, S.; Gu, S.; Mahmud, H.; Wang, K.; Floride, E.; Schleicher, E.; Schulz, E.; Muenzel, T.; Lang, F.
Regulation of erythrocyte survival by AMP-activated protein kinase
FASEB J.
23
1072-1080
2009
Homo sapiens, Mus musculus
Choi, H.C.; Song, P.; Xie, Z.; Wu, Y.; Xu, J.; Zhang, M.; Dong, Y.; Wang, S.; Lau, K.; Zou, M.H.
Reactive nitrogen species is required for the activation of the AMP-activated protein kinase by statin in vivo
J. Biol. Chem.
283
20186-20197
2008
Bos taurus, Homo sapiens, Mus musculus, Mus musculus C57/BL6J
Qin, S.; De Vries, G.W.
alpha2 But not alpha1 AMP-activated protein kinase mediates oxidative stress-induced inhibition of retinal pigment epithelium cell phagocytosis of photoreceptor outer segments
J. Biol. Chem.
283
6744-6751
2008
Homo sapiens
Scharl, M.; Paul, G.; Barrett, K.E.; McCole, D.F.
AMP-activated protein kinase mediates the interferon-gamma-induced decrease in intestinal epithelial barrier function
J. Biol. Chem.
284
27952-27963
2009
Homo sapiens
Kola, B.
Role of AMP-activated protein kinase in the control of appetite
J. Neuroendocrinol.
20
942-951
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Gusarova, G.A.; Dada, L.A.; Kelly, A.M.; Brodie, C.; Witters, L.A.; Chandel, N.S.; Sznajder, J.I.
Alpha1-AMP-activated protein kinase regulates hypoxia-induced Na,K-ATPase endocytosis via direct phosphorylation of protein kinase C zeta
Mol. Cell. Biol.
29
3455-3464
2009
Homo sapiens
Hien, T.T.; Kim, H.G.; Han, E.H.; Kang, K.W.; Jeong, H.G.
Molecular mechanism of suppression of MDR1 by puerarin from Pueraria lobata via NF-kappaB pathway and cAMP-responsive element transcriptional activity-dependent up-regulation of AMP-activated protein kinase in breast cancer MCF-7/adr cells
Mol. Nutr. Food Res.
54
918-928
2010
Homo sapiens
Spasic, M.R.; Callaerts, P.; Norga, K.K.
AMP-activated protein kinase (AMPK) molecular crossroad for metabolic control and survival of neurons
Neuroscientist
15
309-316
2009
Saccharomyces cerevisiae, Homo sapiens, Mus musculus, Rattus norvegicus
Khanal, P.; Oh, W.K.; Thuong, P.T.; Cho, S.D.; Choi, H.S.
24-hydroxyursolic acid from the leaves of the Diospyros kaki (Persimmon) induces apoptosis by activation of AMP-activated protein kinase
Planta Med.
76
689-693
2010
Homo sapiens
Zhang, H.S.; Wu, M.R.
SIRT1 regulates Tat-induced HIV-1 transactivation through activating AMP-activated protein kinase
Virus Res.
146
51-57
2009
Homo sapiens
Handa, N.; Takagi, T.; Saijo, S.; Kishishita, S.; Takaya, D.; Toyama, M.; Terada, T.; Shirouzu, M.; Suzuki, A.; Lee, S.; Yamauchi, T.; Okada-Iwabu, M.; Iwabu, M.; Kadowaki, T.; Minokoshi, Y.; Yokoyama, S.
Structural basis for compound C inhibition of the human AMP-activated protein kinase alpha2 subunit kinase domain
Acta Crystallogr. Sect. D
67
480-487
2011
Homo sapiens (P54646)
Thali, R.F.; Tuerk, R.D.; Scholz, R.; Yoho-Auchli, Y.; Brunisholz, R.A.; Neumann, D.
Novel candidate substrates of AMP-activated protein kinase identified in red blood cell lysates
Biochem. Biophys. Res. Commun.
398
296-301
2010
Homo sapiens (Q13131)
Sano, S.; Sakagami, R.; Sekiguchi, M.; Hidaka, M.
Stabilization of MAPO1 by specific binding with folliculin and AMP-activated protein kinase in O6-methylguanine-induced apoptosis
Biochem. Biophys. Res. Commun.
430
810-815
2013
Homo sapiens (Q13131)
Rajamohan, F.; Reyes, A.R.; Frisbie, R.K.; Hoth, L.R.; Sahasrabudhe, P.; Magyar, R.; Landro, J.A.; Withka, J.M.; Caspers, N.L.; Calabrese, M.F.; Ward, J.; Kurumbail, R.G.
Probing the enzyme kinetics, allosteric modulation and activation of alpha1- and alpha2-subunit-containing AMP-activated protein kinase (AMPK) heterotrimeric complexes by pharmacological and physiological activators
Biochem. J.
473
581-592
2016
Homo sapiens (Q13131 AND P54646)
Yu, D.; Peng, Y.; Ayaz-Guner, S.; Gregorich, Z.R.; Ge, Y.
Comprehensive characterization of AMP-activated protein kinase catalytic domain by top-down mass spectrometry
J. Am. Soc. Mass Spectrom.
27
220-232
2016
Homo sapiens (Q13131)
Alesutan, I.; Foeller, M.; Sopjani, M.; Dermaku-Sopjani, M.; Zelenak, C.; Froehlich, H.; Velic, A.; Fraser, S.; Kemp, B.E.; Seebohm, G.; Voelkl, H.; Lang, F.
Inhibition of the heterotetrameric K+ channel KCNQ1/KCNE1 by the AMP-activated protein kinase
Mol. Membr. Biol.
28
79-89
2011
Homo sapiens (Q13131 AND Q9Y478 AND P54619)
Rajamohan, F.; Harris, M.S.; Frisbie, R.K.; Hoth, L.R.; Geoghegan, K.F.; Valentine, J.J.; Reyes, A.R.; Landro, J.A.; Qiu, X.; Kurumbail, R.G.
Escherichia coli expression, purification and characterization of functional full-length recombinant alpha2beta2gamma3 heterotrimeric complex of human AMP-activated protein kinase
Protein Expr. Purif.
73
189-197
2010
Homo sapiens (P54646 AND O43741 AND Q9UGI9)
Matheson, C.J.; Casalvieri, K.A.; Backos, D.S.; Minhajuddin, M.; Jordan, C.T.; Reigan, P.
Substituted oxindol-3-ylidenes as AMP-activated protein kinase (AMPK) inhibitors
Eur. J. Med. Chem.
197
112316
2020
Homo sapiens (P54646), Homo sapiens (Q13131)
Chen, M.; Liu, J.; Yang, L.; Ling, W.
AMP-activated protein kinase regulates lipid metabolism and the fibrotic phenotype of hepatic stellate cells through inhibition of autophagy
FEBS Open Bio
7
811-820
2017
Homo sapiens
Han, J.S.; Sung, J.H.; Lee, S.K.
Inhibition of cholesterol synthesis in HepG2 cells by GINST-decreasing HMG-CoA reductase expression via AMP-activated protein kinase
J. Food Sci.
82
2700-2705
2017
Homo sapiens
Singh, S.; Singh, P.K.; Suhail, H.; Arumugaswami, V.; Pellett, P.E.; Giri, S.; Kumar, A.
Adenosine monophosphate-activated protein kinase restricts Zika virus replication in endothelial cells by potentiating innate antiviral responses and inhibiting glycolysis
J. Immunol.
204
1810-1824
2020
Homo sapiens
EXTERNAL LINKS (specific for EC-Number 2.7.11.31)
Transporter Classification Database (TCDB): 8.A.104.1.1
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
