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General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Gene namei
Official gene symbol, which is typically a short form of the gene name, according to HGNC.
Protein kinase AMP-activated catalytic subunit alpha 2
Protein classi
Assigned HPA protein class(es) for the encoded protein(s).
Enzymes FDA approved drug targets Transporters
Predicted locationi
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Chromosome
1
Cytoband
p32.2
Chromosome location (bp)
56645314 - 56715335
Number of transcriptsi
Number of protein-coding transcripts from the gene as defined by Ensembl.
Useful information about the protein provided by UniProt.
Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism 1,2. 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 3,4. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators 5,6. 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 7. Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) 8. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). Involved in insulin receptor/INSR internalization 9. 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 10,11,12,13,14. 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 FNIP1, TSC2, RPTOR, WDR24 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 15,16,17. Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation 18. In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes 19. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 20. In that process also activates WDR45/WIPI4 21. Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation 22. 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 23. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 24,25. 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). Upon glucose starvation, promotes ARF6 activation in a kinase-independent manner leading to cell migration 26. Upon glucose deprivation mediates the phosphorylation of ACSS2 at 'Ser-659', which exposes the nuclear localization signal of ACSS2, required for its interaction with KPNA1 and nuclear translocation 27. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L 28....show less
Molecular function (UniProt)i
Keywords assigned by UniProt to proteins due to their particular molecular function.
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, Jul 2008]...show less
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The Splice variant identifier links to the Ensembl website protein summary for the selected splice variant. The data in the Swissprot and TrEMBL columns links to corresponding pages in the UniProt database.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide and number of predicted transmembrane region(s) according to in-house majority decision methods based on sets of predictors are also reported.
P54646 [Direct mapping] 5'-AMP-activated protein kinase catalytic subunit alpha-2
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Enzymes ENZYME proteins Transferases Kinases CAMK Ser/Thr protein kinases Transporters Accessory Factors Involved in Transport Predicted membrane proteins Prediction method-based Membrane proteins predicted by MDM MEMSAT-SVM predicted membrane proteins SCAMPI predicted membrane proteins SPOCTOPUS predicted membrane proteins THUMBUP predicted membrane proteins # TM segments-based 1TM proteins predicted by MDM FDA approved drug targets Small molecule drugs Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0000166[nucleotide binding] GO:0003682[chromatin binding] GO:0004672[protein kinase activity] GO:0004674[protein serine/threonine kinase activity] GO:0004679[AMP-activated protein kinase activity] GO:0004712[protein serine/threonine/tyrosine kinase activity] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005634[nucleus] GO:0005654[nucleoplasm] GO:0005737[cytoplasm] GO:0005794[Golgi apparatus] GO:0005829[cytosol] GO:0006325[chromatin organization] GO:0006468[protein phosphorylation] GO:0006629[lipid metabolic process] GO:0006631[fatty acid metabolic process] GO:0006633[fatty acid biosynthetic process] GO:0006694[steroid biosynthetic process] GO:0006695[cholesterol biosynthetic process] GO:0006914[autophagy] GO:0007165[signal transduction] GO:0008202[steroid metabolic process] GO:0008203[cholesterol metabolic process] GO:0008610[lipid biosynthetic process] GO:0010468[regulation of gene expression] GO:0010494[cytoplasmic stress granule] GO:0010508[positive regulation of autophagy] GO:0010629[negative regulation of gene expression] GO:0014850[response to muscle activity] GO:0016055[Wnt signaling pathway] GO:0016126[sterol biosynthetic process] GO:0016239[positive regulation of macroautophagy] GO:0016241[regulation of macroautophagy] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016570[histone modification] GO:0016607[nuclear speck] GO:0016740[transferase activity] GO:0030424[axon] GO:0030425[dendrite] GO:0031331[positive regulation of cellular catabolic process] GO:0031588[nucleotide-activated protein kinase complex] GO:0031669[cellular response to nutrient levels] GO:0032007[negative regulation of TOR signaling] GO:0034599[cellular response to oxidative stress] GO:0035174[histone serine kinase activity] GO:0035556[intracellular signal transduction] GO:0042149[cellular response to glucose starvation] GO:0042593[glucose homeostasis] GO:0042752[regulation of circadian rhythm] GO:0043025[neuronal cell body] GO:0043066[negative regulation of apoptotic process] GO:0045821[positive regulation of glycolytic process] GO:0046872[metal ion binding] GO:0047322[[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity] GO:0048511[rhythmic process] GO:0050405[[acetyl-CoA carboxylase] kinase activity] GO:0055089[fatty acid homeostasis] GO:0062028[regulation of stress granule assembly] GO:0070507[regulation of microtubule cytoskeleton organization] GO:0071277[cellular response to calcium ion] GO:0071333[cellular response to glucose stimulus] GO:0071380[cellular response to prostaglandin E stimulus] GO:0071466[cellular response to xenobiotic stimulus] GO:0097009[energy homeostasis] GO:0106310[protein serine kinase activity] GO:1903829[positive regulation of protein localization] GO:1904428[negative regulation of tubulin deacetylation] GO:1905691[lipid droplet disassembly] GO:1990044[protein localization to lipid droplet] GO:2000758[positive regulation of peptidyl-lysine acetylation]
The Human Protein Atlas project is funded
