PRKAA2

The protein encoded by this gene is a catalytic subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. Studies of the mouse counterpart suggest that this catalytic subunit may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia. [provided by RefSeq]

protein kinase, AMP-activated, alpha 2 catalytic subunit

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 (PubMed:7959015).
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).
Involved in insulin receptor/INSR internalization (PubMed:25687571).
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: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).
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 acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097).
Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060).
Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation (By similarity).
Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity).

AutophagyIEA:UniProtKB-KW
Cellular response to calcium ionISS:ARUK-UCL
Cellular response to glucose starvationManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to glucose stimulusISS:ARUK-UCL
Cellular response to nutrient levelsManual Assertion Based On ExperimentIDA:ComplexPortal
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
Energy homeostasisISS:UniProtKB
Fatty acid biosynthetic processIEA:UniProtKB-KW
Fatty acid homeostasisISS:UniProtKB
Glucose homeostasisISS:UniProtKB
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Lipid biosynthetic processISS:UniProtKB
Lipid droplet disassemblyManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of apoptotic processISS:UniProtKB
Negative regulation of gene expressionISS:ARUK-UCL
Negative regulation of TOR signalingISS:UniProtKB
Negative regulation of tubulin deacetylationISS:ARUK-UCL
Positive regulation of autophagyISS:UniProtKB
Positive regulation of glycolytic processISS:UniProtKB
Positive regulation of macroautophagyManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Positive regulation of peptidyl-lysine acetylationISS:ARUK-UCL
Positive regulation of protein localizationISS:ARUK-UCL
Protein localization to lipid dropletManual Assertion Based On ExperimentIDA:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of circadian rhythmISS:UniProtKB
Regulation of macroautophagyISS:UniProtKB
Regulation of microtubule cytoskeleton organizationISS:ARUK-UCL
Regulation of stress granule assemblyIEA:Ensembl
Response to muscle activityIEA: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-172 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-172 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-172, but at much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. Dephosphorylated by PPM1A and PPM1B at Thr-172 (mediated by STK11/LKB1).