AMPKalpha (SNF1A) is the single catalytic alpha subunit of Drosophila AMP-activated protein kinase, a heterotrimeric serine/threonine kinase (with the beta subunit Alicorn and the gamma subunit SNF4Agamma) that senses cellular energy status. AMPKalpha is activated by phosphorylation of Thr184 in its activation loop by LKB1 and by AMP binding to the gamma subunit when ATP is depleted. The active kinase phosphorylates metabolic and signalling substrates, including acetyl-CoA carboxylase, the TSC2 homolog Gigas, and myosin regulatory light chain, thereby inhibiting TORC1-dependent anabolic growth, promoting autophagy and lipid catabolism, and maintaining energy homeostasis. It is present in the cytoplasm and nucleus. In the whole animal AMPKalpha is required for viability, starvation resistance and feeding/locomotor behaviour, visceral muscle function and nutrient uptake, mitosis, and maintenance of neurons including dendrites.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000166 nucleotide binding | IEA GO_REF:0000104 | ACCEPT | Summary: Nucleotide/ATP binding inferred from the protein kinase domain. Reason: ATP is the phosphate donor for the kinase activity; appropriate electronic inference. |
| GO:0000278 mitotic cell cycle | IMP PMID:17486097 Energy-dependent regulation of cell structure by AMP-activat... | KEEP AS NON CORE | Summary: AMPK-null mutants show mitotic abnormalities. Reason: Supported by mutant analysis, but a pleiotropic consequence of AMPK loss rather than a core process. Supporting Evidence: PMID:17486097 AMPK-null mutants were lethal with severe abnormalities in cell polarity and mitosis, similar to those of lkb1-null mutants. |
| GO:0001558 regulation of cell growth | IMP PMID:20478298 AMPK supports growth in Drosophila by regulating muscle acti... | KEEP AS NON CORE | Summary: dAMPKalpha mutants are small, and AMPKalpha acts nonautonomously to support cell growth. Reason: Organismal growth phenotype mediated by visceral muscle function and nutrient uptake; non-core. Supporting Evidence: PMID:20478298 dAMPKalpha functions as a nonautonomous regulator of cell growth |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: General kinase/transferase activity inferred from the kinase domain. Reason: Correct but a general parent; MODIFY to AMP-activated protein kinase activity, which AMPKalpha already carries (IDA, IEA, IMP). Proposed replacements: AMP-activated protein kinase activity |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | MODIFY | Summary: AMPKalpha is a serine/threonine protein kinase. Reason: Supported by phylogeny and by direct kinase assays, but AMP-activated protein kinase activity is the more specific supported term; MODIFY to it, which AMPKalpha already carries (IDA, IEA, IMP). Proposed replacements: AMP-activated protein kinase activity |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: AMPKalpha is a serine/threonine protein kinase. Reason: Supported by phylogeny and by direct kinase assays, but AMP-activated protein kinase activity is the more specific supported term; MODIFY to it, which AMPKalpha already carries (IDA, IEA, IMP). Proposed replacements: AMP-activated protein kinase activity |
| GO:0004679 AMP-activated protein kinase activity | IDA PMID:25826530 Identification of an AMPK phosphorylation site in Drosophila... | ACCEPT | Summary: AMPKalpha is the catalytic subunit of Drosophila AMPK, activated by AMP and ATP depletion and phosphorylating SAMS peptide, ACC and Gigas/TSC2. Reason: Core function, supported by RNAi ablation of AMPK activity in cell extracts and by in vitro phosphorylation of Gigas Ser1338. Supporting Evidence: PMID:12093363 The Drosophila kinase (DmAMPK) was activated by AMP in cell-free assays (albeit to a smaller extent than mammalian AMPK), and by stresses that deplete ATP (oligomycin and hypoxia), as well as by carbohydrate deprivation, in intact cells. PMID:25826530 phosphorylated by AMPK in vitro file:DROME/AMPKalpha/AMPKalpha-deep-research-falcon.md encodes the catalytic alpha subunit of the conserved heterotrimeric AMP-activated protein kinase (AMPK) complex |
| GO:0004679 AMP-activated protein kinase activity | IDA PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ... | ACCEPT | Summary: AMPKalpha is the catalytic subunit of Drosophila AMPK, activated by AMP and ATP depletion and phosphorylating SAMS peptide, ACC and Gigas/TSC2. Reason: Core function, supported by RNAi ablation of AMPK activity in cell extracts and by in vitro phosphorylation of Gigas Ser1338. Supporting Evidence: PMID:12093363 The Drosophila kinase (DmAMPK) was activated by AMP in cell-free assays (albeit to a smaller extent than mammalian AMPK), and by stresses that deplete ATP (oligomycin and hypoxia), as well as by carbohydrate deprivation, in intact cells. PMID:25826530 phosphorylated by AMPK in vitro file:DROME/AMPKalpha/AMPKalpha-deep-research-falcon.md encodes the catalytic alpha subunit of the conserved heterotrimeric AMP-activated protein kinase (AMPK) complex |
| GO:0004679 AMP-activated protein kinase activity | IEA GO_REF:0000117 | ACCEPT | Summary: AMPKalpha is the catalytic subunit of Drosophila AMPK, activated by AMP and ATP depletion and phosphorylating SAMS peptide, ACC and Gigas/TSC2. Reason: Core function, supported by RNAi ablation of AMPK activity in cell extracts and by in vitro phosphorylation of Gigas Ser1338. Supporting Evidence: PMID:12093363 The Drosophila kinase (DmAMPK) was activated by AMP in cell-free assays (albeit to a smaller extent than mammalian AMPK), and by stresses that deplete ATP (oligomycin and hypoxia), as well as by carbohydrate deprivation, in intact cells. PMID:25826530 phosphorylated by AMPK in vitro file:DROME/AMPKalpha/AMPKalpha-deep-research-falcon.md encodes the catalytic alpha subunit of the conserved heterotrimeric AMP-activated protein kinase (AMPK) complex |
| GO:0004679 AMP-activated protein kinase activity | IMP PMID:12093363 A homologue of AMP-activated protein kinase in Drosophila me... | ACCEPT | Summary: AMPKalpha is the catalytic subunit of Drosophila AMPK, activated by AMP and ATP depletion and phosphorylating SAMS peptide, ACC and Gigas/TSC2. Reason: Core function, supported by RNAi ablation of AMPK activity in cell extracts and by in vitro phosphorylation of Gigas Ser1338. Supporting Evidence: PMID:12093363 The Drosophila kinase (DmAMPK) was activated by AMP in cell-free assays (albeit to a smaller extent than mammalian AMPK), and by stresses that deplete ATP (oligomycin and hypoxia), as well as by carbohydrate deprivation, in intact cells. PMID:25826530 phosphorylated by AMPK in vitro file:DROME/AMPKalpha/AMPKalpha-deep-research-falcon.md encodes the catalytic alpha subunit of the conserved heterotrimeric AMP-activated protein kinase (AMPK) complex |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: Nucleotide/ATP binding inferred from the protein kinase domain. Reason: ATP is the phosphate donor for the kinase activity; appropriate electronic inference. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Phosphorylated (active) AMPKalpha is detected mainly in the nucleus of stressed Drosophila cells. Reason: Direct IDA and IBA; AMPK acts in both nucleus and cytoplasm. Supporting Evidence: PMID:12093363 the phosphorylated DmAMPK alpha subunit was mainly detected in the nucleus |
| GO:0005634 nucleus | IDA PMID:12093363 A homologue of AMP-activated protein kinase in Drosophila me... | ACCEPT | Summary: Phosphorylated (active) AMPKalpha is detected mainly in the nucleus of stressed Drosophila cells. Reason: Direct IDA and IBA; AMPK acts in both nucleus and cytoplasm. Supporting Evidence: PMID:12093363 the phosphorylated DmAMPK alpha subunit was mainly detected in the nucleus |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: AMPKalpha acts in the cytoplasm. Reason: AMPK phosphorylates cytoplasmic substrates (ACC, MRLC, Gigas); IBA and IEA consistent. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: AMPKalpha acts in the cytoplasm. Reason: AMPK phosphorylates cytoplasmic substrates (ACC, MRLC, Gigas); IBA and IEA consistent. |
| GO:0005768 endosome | IDA PMID:29084199 Class III phosphatidylinositol-3-OH kinase controls epitheli... | KEEP AS NON CORE | Summary: Endosomal localization reported in a study of CIII-PI3K and endosomal LKB1 regulation. Reason: Curators recorded endosomal AMPK localization from the full text; the cached abstract focuses on endosomal LKB1. Plausible but not a core location. |
| GO:0006629 lipid metabolic process | IMP PMID:20862213 Altered metabolism and persistent starvation behaviors cause... | KEEP AS NON CORE | Summary: Reduced AMPK function lowers triglyceride levels and alters lipid accumulation. Reason: Metabolic consequence of reduced AMPK signalling; supported but non-core. Supporting Evidence: PMID:20862213 Unexpectedly, total dietary intake was greater in animals with reduced AMPK function yet total triglyceride levels were lower. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ... | MODIFY | Summary: Proliferation annotation from a study of LKB1 phosphorylation by PDK1 and its effect on AMPK. Reason: The paper's title ("Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation and Organ Growth by Decreased Activation of AMPK") reads as if AMPK promotes proliferation, but its Results and Discussion say the opposite. Decreased AMPK/mTOR activation leads to increased cell size and proliferation, and overactivation of the AMPK axis reduces body size by decreasing proliferation. This matches the same paper's TORC1 data (enhanced AMPK, decreased mTOR) on which the GO:1904263 to GO:1904262 correction is based. AMPK therefore negatively regulates cell population proliferation in this system, a context-specific, non-core role. The same row on Lkb1 (the upstream kinase that activates AMPK in this pathway) is modified to the same term. Proposed replacements: negative regulation of cell population proliferation Supporting Evidence: PMID:36899949 thus resulting in decreased activation of AMPK and its downstream target mTOR, which leads to increased cell size and proliferation PMID:36899949 adult flies exhibit a reduced body size due to decreased cell proliferation upon overactivation of the AMPK/mTOR axis |
| GO:0009267 cellular response to starvation | IMP PMID:20862213 Altered metabolism and persistent starvation behaviors cause... | ACCEPT | Summary: AMPK is required for organismal and cellular responses to starvation. Reason: Responding to energy deprivation is the defining role of AMPK; supported by mutant data in whole flies and in cortex glia. Supporting Evidence: PMID:20862213 Reduced AMPK signaling leads to hypersensitivity to starvation conditions as measured by lifespan and locomotor activity. PMID:35177854 KB production and delivery in cortex glia are regulated by AMP-activated protein kinase (AMPK), the cellular master energy sensor |
| GO:0009267 cellular response to starvation | IMP PMID:35177854 Glia fuel neurons with locally synthesized ketone bodies to ... | ACCEPT | Summary: AMPK is required for organismal and cellular responses to starvation. Reason: Responding to energy deprivation is the defining role of AMPK; supported by mutant data in whole flies and in cortex glia. Supporting Evidence: PMID:20862213 Reduced AMPK signaling leads to hypersensitivity to starvation conditions as measured by lifespan and locomotor activity. PMID:35177854 KB production and delivery in cortex glia are regulated by AMP-activated protein kinase (AMPK), the cellular master energy sensor |
| GO:0010508 positive regulation of autophagy | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for positive regulation of autophagy. Reason: Conserved AMPK function (via Atg1/ULK1 phosphorylation and TORC1 inhibition); consistent with fly gamma-subunit autophagy data (PMID:18285699). |
| GO:0016239 positive regulation of macroautophagy | ISS PMID:36493962 Atg1 phosphorylation is activated by AMPK and indispensable ... | ACCEPT | Summary: AMPK phosphorylates and activates Atg1 to induce autophagy (by similarity to Bombyx). Reason: Conserved mechanism; Atg1 phosphorylation sites activated by AMPK are evolutionarily conserved. Supporting Evidence: PMID:36493962 two BmAtg1c phosphorylation sites were identified at Ser269 and Ser270, which were activated by BmAMPK, the major energy-sensing kinase |
| GO:0016301 kinase activity | IEA GO_REF:0000104 | MODIFY | Summary: General kinase/transferase activity inferred from the kinase domain. Reason: Correct but a general parent; MODIFY to AMP-activated protein kinase activity, which AMPKalpha already carries (IDA, IEA, IMP). Proposed replacements: AMP-activated protein kinase activity |
| GO:0016740 transferase activity | IEA GO_REF:0000104 | MODIFY | Summary: General kinase/transferase activity inferred from the kinase domain. Reason: Correct but a general parent; MODIFY to AMP-activated protein kinase activity, which AMPKalpha already carries (IDA, IEA, IMP). Proposed replacements: AMP-activated protein kinase activity |
| GO:0030730 triglyceride storage | IMP PMID:20862213 Altered metabolism and persistent starvation behaviors cause... | KEEP AS NON CORE | Summary: Reduced AMPK function lowers triglyceride levels and alters lipid accumulation. Reason: Metabolic consequence of reduced AMPK signalling; supported but non-core. Supporting Evidence: PMID:20862213 Unexpectedly, total dietary intake was greater in animals with reduced AMPK function yet total triglyceride levels were lower. |
| GO:0031588 nucleotide-activated protein kinase complex | IBA GO_REF:0000033 | ACCEPT | Summary: AMPKalpha is the catalytic subunit of the heterotrimeric AMPK complex. Reason: RNAi against any of the alpha, beta or gamma subunits ablated DmAMPK activity, supporting a heterotrimeric complex. Supporting Evidence: PMID:12093363 Expression of double stranded (ds) RNAs targeted at any of the putative alpha, beta or gamma subunits ablated this activity PMID:27729213 AMP-activated protein kinase (AMPK) is a heterotrimeric complex that is activated in response to low energy levels |
| GO:0031588 nucleotide-activated protein kinase complex | IC PMID:12093363 A homologue of AMP-activated protein kinase in Drosophila me... | ACCEPT | Summary: AMPKalpha is the catalytic subunit of the heterotrimeric AMPK complex. Reason: RNAi against any of the alpha, beta or gamma subunits ablated DmAMPK activity, supporting a heterotrimeric complex. Supporting Evidence: PMID:12093363 Expression of double stranded (ds) RNAs targeted at any of the putative alpha, beta or gamma subunits ablated this activity PMID:27729213 AMP-activated protein kinase (AMPK) is a heterotrimeric complex that is activated in response to low energy levels |
| GO:0031588 nucleotide-activated protein kinase complex | NAS PMID:27729213 AMP-activated protein kinase has diet-dependent and -indepen... | ACCEPT | Summary: AMPKalpha is the catalytic subunit of the heterotrimeric AMPK complex. Reason: RNAi against any of the alpha, beta or gamma subunits ablated DmAMPK activity, supporting a heterotrimeric complex. Supporting Evidence: PMID:12093363 Expression of double stranded (ds) RNAs targeted at any of the putative alpha, beta or gamma subunits ablated this activity PMID:27729213 AMP-activated protein kinase (AMPK) is a heterotrimeric complex that is activated in response to low energy levels |
| GO:0042149 cellular response to glucose starvation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for cellular response to glucose starvation. Reason: Conserved AMPK/SNF1 function; Drosophila AMPK is activated by carbohydrate deprivation in cells. Supporting Evidence: PMID:12093363 as well as by carbohydrate deprivation, in intact cells |
| GO:0042595 behavioral response to starvation | IMP PMID:20862213 Altered metabolism and persistent starvation behaviors cause... | KEEP AS NON CORE | Summary: Reduced AMPK function alters starvation-induced hyperactivity. Reason: Behavioural phenotype; non-core. Supporting Evidence: PMID:20862213 starvation-induced hyperactivity, an adaptive response to encourage foraging, was significantly higher than in wild type |
| GO:0043050 nematode pharyngeal pumping | IEA GO_REF:0000117 | REMOVE | Summary: Nematode pharyngeal pumping, from automated (ARBA) inference. Reason: Nematode-specific process with no counterpart in Drosophila; taxonomically inappropriate electronic annotation. |
| GO:0044058 regulation of digestive system process | IMP PMID:20478298 AMPK supports growth in Drosophila by regulating muscle acti... | KEEP AS NON CORE | Summary: AMPKalpha in visceral muscle is required for gut peristalsis and nutrient uptake. Reason: Tissue-specific role via MRLC phosphorylation; non-core. Supporting Evidence: PMID:20478298 These data suggest strongly that AMPK regulates visceral smooth muscle function through phosphorylation of MRLC. |
| GO:0045197 establishment or maintenance of epithelial cell apical/basal polarity | IMP PMID:17486097 Energy-dependent regulation of cell structure by AMP-activat... | UNDECIDED | Summary: Original report that AMPK-null epithelial cells lose apical/basal polarity under energetic stress. Reason: The polarity phenotype reported in PMID:17486097 could not be reproduced by a later study, which attributed apparent polarity defects to damaged follicle cell "false clones"; a separate study found that dAMPKalpha mutant gut defects did not stem from altered epithelial polarity. The claim is disputed and we cannot resolve it from the available evidence. Supporting Evidence: PMID:17486097 AMPK-null mutants were lethal with severe abnormalities in cell polarity and mitosis PMID:24337115 In following up on these findings, we observed that AMPK controls cell size in the follicle cell epithelium, but were unable to reproduce the energy-dependent polarity phenotype. |
| GO:0045792 negative regulation of cell size | IMP PMID:24337115 Damage to the Drosophila follicle cell epithelium produces "... | KEEP AS NON CORE | Summary: AMPK controls cell size in the follicle cell epithelium. Reason: Supported by mutant analysis; downstream consequence of TORC1 restraint. Supporting Evidence: PMID:24337115 we observed that AMPK controls cell size in the follicle cell epithelium |
| GO:0048813 dendrite morphogenesis | IMP PMID:24337116 Isolation of AMP-activated protein kinase (AMPK) alleles req... | KEEP AS NON CORE | Summary: AMPKalpha alleles affect dendrite development/maintenance of larval sensory neurons. Reason: Neuronal phenotype from a forward genetic screen; non-core. |
| GO:1902669 positive regulation of axon guidance | IGI PMID:22319582 Diet and energy-sensing inputs affect TorC1-mediated axon mi... | KEEP AS NON CORE | Summary: AMPK genetic manipulations modify TorC1-dependent axon misrouting in a tuberous sclerosis model. Reason: Genetic interaction in a sensitized background; context-specific. Supporting Evidence: PMID:22319582 When ATP levels are low, AMPK reduces the activity of the TOR pathway by promoting the inhibitory functions of TSC1/2. |
| GO:1904262 negative regulation of TORC1 signaling | IBA GO_REF:0000033 | ACCEPT | Summary: AMPK inhibits TORC1 signalling, in part by phosphorylating Gigas/TSC2. Reason: Conserved core output of AMPK, supported by IBA and by identification of an AMPK site in fly TSC2. Supporting Evidence: PMID:25826530 Once activated, AMPK regulates metabolism to adapt to the nutrient-scarce condition; AMPK upregulates catabolism while inhibiting anabolism. |
| GO:1904262 negative regulation of TORC1 signaling | IMP PMID:25826530 Identification of an AMPK phosphorylation site in Drosophila... | ACCEPT | Summary: AMPK inhibits TORC1 signalling, in part by phosphorylating Gigas/TSC2. Reason: Conserved core output of AMPK, supported by IBA and by identification of an AMPK site in fly TSC2. Supporting Evidence: PMID:25826530 Once activated, AMPK regulates metabolism to adapt to the nutrient-scarce condition; AMPK upregulates catabolism while inhibiting anabolism. |
| GO:1904263 positive regulation of TORC1 signaling | IMP PMID:36899949 Phosphorylation of LKB1 by PDK1 Inhibits Cell Proliferation ... | MODIFY | Summary: Positive regulation of TORC1 signaling from a study of LKB1 phosphorylation by PDK1. Reason: In the same study, enhanced AMPK activation is accompanied by decreased mTOR activity; AMPK inhibits TORC1. The sign of this annotation is inverted and should be negative regulation of TORC1 signaling (consistent with the Lkb1, Mo25 and Stlk reviews). Proposed replacements: negative regulation of TORC1 signaling Supporting Evidence: PMID:36899949 Cells expressing phospho-deficient LKB1 consequently display enhanced AMPK activation and decreased mTOR activity, resulting in reduced cell size. |
| GO:1904504 positive regulation of lipophagy | IMP PMID:29503179 Inflammation-Modulated Metabolic Reprogramming Is Required f... | KEEP AS NON CORE | Summary: AMPK is part of a TRAF3-AMPK/WTS-ATG1 pathway driving lipophagy in infected enterocytes. Reason: Context-specific (enteric infection) role; supported by genetic data. Supporting Evidence: PMID:29503179 Infection induces signaling cascades involving TRAF3 and kinases AMPK and WTS, which regulate TOR kinase to control the balance of lipogenesis versus lipolysis. |
| GO:1990044 protein localization to lipid droplet | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for protein localization to lipid droplet. Reason: Phylogenetically inferred; no fly-specific evidence, and not a core activity of the kinase. |
| GO:1990794 basolateral part of cell | IDA PMID:29084199 Class III phosphatidylinositol-3-OH kinase controls epitheli... | KEEP AS NON CORE | Summary: Basolateral localization reported in epithelial cells. Reason: Context-specific subcellular distribution in epithelia; not a core location. |
| GO:2000786 positive regulation of autophagosome assembly | ISS PMID:36493962 Atg1 phosphorylation is activated by AMPK and indispensable ... | KEEP AS NON CORE | Summary: Positive regulation of autophagosome assembly by similarity to Bombyx AMPK. Reason: More specific downstream consequence of Atg1 activation; acceptable but non-core. |
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Download this section (compressed HTML)AMP-activated protein kinase &agr; subunit (AMPK&agr;) encodes the &agr; subunit of the AMP-activated protein kinase (AMPK) complex. In general AMPK helps cells conserve energy through inhibition of energy consuming processes (fatty acid synthesis, protein synthesis). AMPK is usually active when the TOR pathway is inhibited.
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