PRKAA1

The protein encoded by this gene belongs to the ser/thr protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq]

PRKAA1

Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357).
In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357).
AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357).
Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity).
Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757).
Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity).
AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity).
Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11554766, PubMed:11518699, PubMed:15866171, PubMed:17711846, PubMed:18184930).
Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity).
In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity).
Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641).
In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641).
In that process also activates WDR45/WIPI4 (PubMed:28561066).
Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622).
In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity).
Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097).
AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity).
May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity).
Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity).
Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:20074060, PubMed:12519745).

AutophagyIEA:UniProtKB-KW
Bile acid and bile salt transportIEA:Ensembl
Bile acid signaling pathwayIEA:Ensembl
CAMKK-AMPK signaling cascadeManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Cellular response to calcium ionISS:ARUK-UCL
Cellular response to ethanolIEA:Ensembl
Cellular response to glucose starvationManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to glucose stimulusISS:ARUK-UCL
Cellular response to hydrogen peroxideIEA:Ensembl
Cellular response to hypoxiaIEA:Ensembl
Cellular response to nutrient levelsManual Assertion Based On ExperimentIDA:ComplexPortal
Cellular response to organonitrogen compoundIEA:Ensembl
Cellular response to oxidative stressISS:ARUK-UCL
Cellular response to prostaglandin E stimulusIEA:Ensembl
Cellular response to xenobiotic stimulusIEA:Ensembl
Cholesterol biosynthetic processIEA:UniProtKB-KW
Chromatin organizationIEA:UniProtKB-KW
Cold acclimationIEA:Ensembl
Energy homeostasisISS:UniProtKB
Fatty acid biosynthetic processIEA:UniProtKB-KW
Fatty acid homeostasisISS:UniProtKB
Fatty acid oxidationIEA:Ensembl
Glucose homeostasisISS:UniProtKB
Glucose metabolic processIEA:Ensembl
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Lipid biosynthetic processISS:UniProtKB
Lipid droplet disassemblyManual Assertion Based On ExperimentIDA:UniProtKB
Motor behaviorManual Assertion Based On ExperimentIGI:ARUK-UCL
Negative regulation of apoptotic processISS:UniProtKB
Negative regulation of gene expressionISS:ARUK-UCL
Negative regulation of glucosylceramide biosynthetic process1 PublicationNAS:UniProtKB
Negative regulation of hepatocyte apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of insulin receptor signaling pathwayIEA:Ensembl
Negative regulation of lipid catabolic processISS:UniProtKB
Negative regulation of TOR signalingISS:UniProtKB
Negative regulation of tubulin deacetylationISS:ARUK-UCL
Neuron cellular homeostasisManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of autophagyManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of cell population proliferationIEA:Ensembl
Positive regulation of cholesterol biosynthetic process1 PublicationNAS:UniProtKB
Positive regulation of gene expressionManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of glycolytic processISS:UniProtKB
Positive regulation of mitochondrial transcriptionIEA:Ensembl
Positive regulation of peptidyl-lysine acetylationISS:ARUK-UCL
Positive regulation of protein localizationISS:ARUK-UCL
Positive regulation of protein targeting to mitochondrionIEA:Ensembl
Positive regulation of skeletal muscle tissue developmentIEA:Ensembl
Protein localization to lipid dropletManual Assertion Based On ExperimentIDA:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of bile acid secretionIEA:Ensembl
Regulation of circadian rhythmISS:UniProtKB
Regulation of microtubule cytoskeleton organizationISS:ARUK-UCL
Regulation of peptidyl-serine phosphorylationIEA:Ensembl
Regulation of stress granule assemblyIEA:Ensembl
Regulation of vesicle-mediated transportIEA:Ensembl
Response to 17alpha-ethynylestradiolIEA:Ensembl
Response to activityIEA:Ensembl
Response to caffeineIEA:Ensembl
Response to camptothecinIEA:Ensembl
Response to gamma radiationISS:UniProtKB
Response to hypoxia1 PublicationNAS:UniProtKB
Response to UVIEA:Ensembl
Rhythmic processIEA:UniProtKB-KW
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Wnt signaling pathwayIEA:UniProtKB-KW

Cytoplasm
Nucleus
In response to stress, recruited by p53/TP53 to specific promoters.

Ubiquitinated.
Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-183 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. Dephosphorylated by PPM1A and PPM1B.