PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1)

Gene

• Entrez ID: 5562
• Gene name: Protein kinase AMP-activated catalytic subunit alpha 1
• Gene symbol: PRKAA1
• Synonyms: AMPK, AMPK alpha 1, AMPKa1
• Chromosome: 5
• Chromosome location: 5p13.1
• Summary: 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, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006742	hsa-miR-19b-3p	Luciferase reporter assay	20190740
MIRT006742	hsa-miR-19b-3p	Sequencing	20371350
MIRT006742	hsa-miR-19b-3p	HITS-CLIP	22473208
MIRT019393	hsa-miR-148b-3p	Microarray	17612493
MIRT020218	hsa-miR-130b-3p	Sequencing, PAR-CLIP	20371350
MIRT020218	hsa-miR-130b-3p	PAR-CLIP	23446348
MIRT020218	hsa-miR-130b-3p	PAR-CLIP	22012620
MIRT020218	hsa-miR-130b-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT021937	hsa-miR-128-3p	Microarray	17612493
MIRT028534	hsa-miR-30a-5p	Proteomics	18668040
MIRT039458	hsa-miR-652-3p	CLASH	23622248
MIRT044135	hsa-miR-30e-5p	CLASH	23622248
MIRT048377	hsa-miR-29b-3p	CLASH	23622248
MIRT122040	hsa-miR-26a-5p	HITS-CLIP	22473208
MIRT122041	hsa-miR-26b-5p	HITS-CLIP	22473208
MIRT215707	hsa-miR-1-5p	PAR-CLIP	23446348
MIRT215707	hsa-miR-1-5p	PAR-CLIP	22012620
MIRT215707	hsa-miR-1-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT313559	hsa-miR-154-3p	PAR-CLIP	23446348
MIRT313559	hsa-miR-154-3p	PAR-CLIP	22012620
MIRT313559	hsa-miR-154-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT313561	hsa-miR-487a-3p	PAR-CLIP	23446348
MIRT313561	hsa-miR-487a-3p	PAR-CLIP	22012620
MIRT313561	hsa-miR-487a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT470268	hsa-miR-3149	PAR-CLIP	23592263
MIRT470269	hsa-miR-6833-5p	PAR-CLIP	23592263
MIRT470270	hsa-miR-297	PAR-CLIP	23592263
MIRT470271	hsa-miR-675-3p	PAR-CLIP	23592263
MIRT470272	hsa-miR-1298-5p	PAR-CLIP	23592263
MIRT470273	hsa-miR-582-5p	PAR-CLIP	23592263
MIRT470274	hsa-miR-101-3p	PAR-CLIP	23592263
MIRT470275	hsa-miR-3613-5p	PAR-CLIP	23592263
MIRT470276	hsa-miR-3190-3p	PAR-CLIP	23592263
MIRT470277	hsa-miR-567	PAR-CLIP	23592263
MIRT470278	hsa-miR-4781-3p	PAR-CLIP	23592263
MIRT470279	hsa-miR-299-3p	PAR-CLIP	23592263
MIRT470280	hsa-miR-4657	PAR-CLIP	23592263
MIRT470281	hsa-miR-4491	PAR-CLIP	23592263
MIRT521687	hsa-miR-1305	PAR-CLIP	23446348
MIRT521687	hsa-miR-1305	PAR-CLIP	22012620
MIRT521687	hsa-miR-1305	PAR-CLIP, HITS-CLIP	21572407
MIRT521687	hsa-miR-1305	PAR-CLIP	20371350
MIRT521688	hsa-miR-607	PAR-CLIP	23446348
MIRT521688	hsa-miR-607	PAR-CLIP	22012620
MIRT521688	hsa-miR-607	PAR-CLIP	21572407
MIRT521688	hsa-miR-607	PAR-CLIP	20371350
MIRT521689	hsa-miR-195-3p	PAR-CLIP	23446348
MIRT521689	hsa-miR-195-3p	PAR-CLIP	22012620
MIRT521689	hsa-miR-195-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521689	hsa-miR-195-3p	PAR-CLIP	20371350
MIRT521690	hsa-miR-16-2-3p	PAR-CLIP	23446348
MIRT521690	hsa-miR-16-2-3p	PAR-CLIP	22012620
MIRT521690	hsa-miR-16-2-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521690	hsa-miR-16-2-3p	PAR-CLIP	20371350
MIRT521691	hsa-miR-8063	PAR-CLIP	23446348
MIRT521691	hsa-miR-8063	PAR-CLIP	22012620
MIRT521691	hsa-miR-8063	PAR-CLIP, HITS-CLIP	21572407
MIRT521691	hsa-miR-8063	PAR-CLIP	20371350
MIRT521692	hsa-miR-4698	PAR-CLIP	23446348
MIRT521692	hsa-miR-4698	PAR-CLIP	22012620
MIRT521692	hsa-miR-4698	PAR-CLIP, HITS-CLIP	21572407
MIRT521692	hsa-miR-4698	PAR-CLIP	20371350
MIRT521693	hsa-miR-519c-3p	PAR-CLIP	23446348
MIRT521693	hsa-miR-519c-3p	PAR-CLIP	22012620
MIRT521693	hsa-miR-519c-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521693	hsa-miR-519c-3p	PAR-CLIP	20371350
MIRT521694	hsa-miR-519b-3p	PAR-CLIP	23446348
MIRT521694	hsa-miR-519b-3p	PAR-CLIP	22012620
MIRT521694	hsa-miR-519b-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521694	hsa-miR-519b-3p	PAR-CLIP	20371350
MIRT521695	hsa-miR-519a-3p	PAR-CLIP	23446348
MIRT521695	hsa-miR-519a-3p	PAR-CLIP	22012620
MIRT521695	hsa-miR-519a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521695	hsa-miR-519a-3p	PAR-CLIP	20371350
MIRT521696	hsa-miR-301b-3p	PAR-CLIP	23446348
MIRT521696	hsa-miR-301b-3p	PAR-CLIP	22012620
MIRT521696	hsa-miR-301b-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521696	hsa-miR-301b-3p	PAR-CLIP	20371350
MIRT521697	hsa-miR-454-3p	PAR-CLIP	23446348
MIRT521697	hsa-miR-454-3p	PAR-CLIP	22012620
MIRT521697	hsa-miR-454-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521697	hsa-miR-454-3p	PAR-CLIP	20371350
MIRT521698	hsa-miR-4295	PAR-CLIP	23446348
MIRT521698	hsa-miR-4295	PAR-CLIP	22012620
MIRT521698	hsa-miR-4295	PAR-CLIP, HITS-CLIP	21572407
MIRT521698	hsa-miR-4295	PAR-CLIP	20371350
MIRT521699	hsa-miR-3666	PAR-CLIP	23446348
MIRT521699	hsa-miR-3666	PAR-CLIP	22012620
MIRT521699	hsa-miR-3666	PAR-CLIP, HITS-CLIP	21572407
MIRT521699	hsa-miR-3666	PAR-CLIP	20371350
MIRT521700	hsa-miR-301a-3p	PAR-CLIP	23446348
MIRT521700	hsa-miR-301a-3p	PAR-CLIP	22012620
MIRT521700	hsa-miR-301a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521700	hsa-miR-301a-3p	PAR-CLIP	20371350
MIRT521701	hsa-miR-130a-3p	PAR-CLIP	23446348
MIRT521701	hsa-miR-130a-3p	PAR-CLIP	22012620
MIRT521701	hsa-miR-130a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT521701	hsa-miR-130a-3p	PAR-CLIP	20371350
MIRT535040	hsa-miR-524-5p	PAR-CLIP	22012620
MIRT535041	hsa-miR-520d-5p	PAR-CLIP	22012620
MIRT535042	hsa-miR-561-3p	PAR-CLIP	22012620
MIRT555221	hsa-miR-4638-3p	PAR-CLIP	21572407
MIRT555221	hsa-miR-4638-3p	PAR-CLIP	20371350
MIRT555222	hsa-miR-3690	PAR-CLIP	21572407
MIRT555223	hsa-miR-6838-5p	PAR-CLIP	21572407
MIRT555223	hsa-miR-6838-5p	PAR-CLIP	20371350
MIRT555224	hsa-miR-497-5p	PAR-CLIP	21572407
MIRT555224	hsa-miR-497-5p	PAR-CLIP	20371350
MIRT555225	hsa-miR-424-5p	PAR-CLIP	21572407
MIRT555225	hsa-miR-424-5p	PAR-CLIP	20371350
MIRT555226	hsa-miR-195-5p	PAR-CLIP	21572407
MIRT555226	hsa-miR-195-5p	PAR-CLIP	20371350
MIRT555227	hsa-miR-16-5p	PAR-CLIP	21572407
MIRT555227	hsa-miR-16-5p	PAR-CLIP	20371350
MIRT555228	hsa-miR-15b-5p	PAR-CLIP	21572407
MIRT555228	hsa-miR-15b-5p	PAR-CLIP	20371350
MIRT555229	hsa-miR-15a-5p	PAR-CLIP	21572407
MIRT555229	hsa-miR-15a-5p	PAR-CLIP	20371350
MIRT555230	hsa-miR-451b	PAR-CLIP	21572407
MIRT555230	hsa-miR-451b	PAR-CLIP	20371350
MIRT555231	hsa-miR-548e-5p	PAR-CLIP	21572407
MIRT555231	hsa-miR-548e-5p	PAR-CLIP	20371350
MIRT726855	hsa-miR-19a-3p	HITS-CLIP	22473208
MIRT732687	hsa-miR-33a-5p	Luciferase reporter assay, qRT-PCR, Western blot	27199118
MIRT733489	hsa-miR-9-5p	Immunofluorescence, qRT-PCR, Western blot	27394443
MIRT735470	hsa-miR-137	Luciferase reporter assay, qRT-PCR, Western blot	27497953

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000187	Process	Activation of MAPK activity	NAS	11546797
GO:0001666	Process	Response to hypoxia	NAS	8557660
GO:0003682	Function	Chromatin binding	ISS
GO:0004672	Function	Protein kinase activity	IDA	17028174
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004679	Function	AMP-activated protein kinase activity	IDA	18439900
GO:0004679	Function	AMP-activated protein kinase activity	ISS
GO:0004679	Function	AMP-activated protein kinase activity	TAS	21768291
GO:0004691	Function	CAMP-dependent protein kinase activity	NAS	8557660
GO:0005515	Function	Protein binding	IPI	16306228, 17028174, 18403135, 18439900, 18480843, 18663353, 19914239, 20562859, 21988832, 22363791, 22939624, 23455922, 24722188, 25416956, 25751139, 25751140, 25852190, 28561066, 29892012, 31515488
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	ISS
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005737	Component	Cytoplasm	IDA	21768291
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006006	Process	Glucose metabolic process	IEA
GO:0006468	Process	Protein phosphorylation	IBA	21873635
GO:0006468	Process	Protein phosphorylation	IDA	17028174
GO:0006633	Process	Fatty acid biosynthetic process	IEA
GO:0006695	Process	Cholesterol biosynthetic process	IEA
GO:0007050	Process	Cell cycle arrest	TAS
GO:0007165	Process	Signal transduction	TAS	8557660
GO:0008022	Function	Protein C-terminus binding	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	IEA
GO:0008610	Process	Lipid biosynthetic process	ISS
GO:0009411	Process	Response to UV	IEA
GO:0009631	Process	Cold acclimation	IEA
GO:0010332	Process	Response to gamma radiation	ISS
GO:0010508	Process	Positive regulation of autophagy	IDA	22012985
GO:0010508	Process	Positive regulation of autophagy	IMP	26103054
GO:0010508	Process	Positive regulation of autophagy	ISS
GO:0010628	Process	Positive regulation of gene expression	IDA	17028174
GO:0010629	Process	Negative regulation of gene expression	ISS
GO:0014823	Process	Response to activity	IEA
GO:0015721	Process	Bile acid and bile salt transport	IEA
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0016236	Process	Macroautophagy	TAS
GO:0016241	Process	Regulation of macroautophagy	TAS
GO:0016324	Component	Apical plasma membrane	IEA
GO:0016607	Component	Nuclear speck	IDA
GO:0019395	Process	Fatty acid oxidation	IEA
GO:0030424	Component	Axon	ISS
GO:0030425	Component	Dendrite	ISS
GO:0031000	Process	Response to caffeine	IEA
GO:0031588	Component	Nucleotide-activated protein kinase complex	ISS
GO:0031588	Component	Nucleotide-activated protein kinase complex	TAS	21768291
GO:0031669	Process	Cellular response to nutrient levels	ISS
GO:0032007	Process	Negative regulation of TOR signaling	ISS
GO:0033135	Process	Regulation of peptidyl-serine phosphorylation	IEA
GO:0034599	Process	Cellular response to oxidative stress	ISS
GO:0035174	Function	Histone serine kinase activity	ISS
GO:0035404	Process	Histone-serine phosphorylation	IEA
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0035690	Process	Cellular response to drug	IEA
GO:0038183	Process	Bile acid signaling pathway	IEA
GO:0042149	Process	Cellular response to glucose starvation	ISS
GO:0042593	Process	Glucose homeostasis	ISS
GO:0042752	Process	Regulation of circadian rhythm	ISS
GO:0043025	Component	Neuronal cell body	ISS
GO:0043066	Process	Negative regulation of apoptotic process	ISS
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045542	Process	Positive regulation of cholesterol biosynthetic process	NAS	8557660
GO:0045821	Process	Positive regulation of glycolytic process	ISS
GO:0046318	Process	Negative regulation of glucosylceramide biosynthetic process	NAS	11165240
GO:0046627	Process	Negative regulation of insulin receptor signaling pathway	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0047322	Function	[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity	IEA
GO:0048156	Function	Tau protein binding	NAS	28386764
GO:0048511	Process	Rhythmic process	IEA
GO:0048643	Process	Positive regulation of skeletal muscle tissue development	IEA
GO:0050321	Function	Tau-protein kinase activity	NAS	28386764
GO:0050405	Function	[acetyl-CoA carboxylase] kinase activity	IEA
GO:0050995	Process	Negative regulation of lipid catabolic process	ISS
GO:0055089	Process	Fatty acid homeostasis	ISS
GO:0060627	Process	Regulation of vesicle-mediated transport	IEA
GO:0061744	Process	Motor behavior	IGI	21768291
GO:0061762	Process	CAMKK-AMPK signaling cascade	IC	22012985
GO:0061762	Process	CAMKK-AMPK signaling cascade	IMP	26103054
GO:0061762	Process	CAMKK-AMPK signaling cascade	TAS	21768291
GO:0062028	Process	Regulation of stress granule assembly	IEA
GO:0070050	Process	Neuron cellular homeostasis	IGI	21768291
GO:0070301	Process	Cellular response to hydrogen peroxide	IEA
GO:0070507	Process	Regulation of microtubule cytoskeleton organization	ISS
GO:0071277	Process	Cellular response to calcium ion	ISS
GO:0071333	Process	Cellular response to glucose stimulus	ISS
GO:0071361	Process	Cellular response to ethanol	IEA
GO:0071380	Process	Cellular response to prostaglandin E stimulus	IEA
GO:0071417	Process	Cellular response to organonitrogen compound	IEA
GO:0071456	Process	Cellular response to hypoxia	IEA
GO:0097009	Process	Energy homeostasis	ISS
GO:0097009	Process	Energy homeostasis	TAS	21768291
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0106311	Function	Protein threonine kinase activity	IEA
GO:0120188	Process	Regulation of bile acid secretion	IEA
GO:1901563	Process	Response to camptothecin	IEA
GO:1901796	Process	Regulation of signal transduction by p53 class mediator	TAS
GO:1903109	Process	Positive regulation of mitochondrial transcription	IEA
GO:1903829	Process	Positive regulation of cellular protein localization	ISS
GO:1903955	Process	Positive regulation of protein targeting to mitochondrion	IEA
GO:1904428	Process	Negative regulation of tubulin deacetylation	ISS
GO:1904486	Process	Response to 17alpha-ethynylestradiol	IEA
GO:2000758	Process	Positive regulation of peptidyl-lysine acetylation	ISS

Other IDs

• MIM: 602739
• HGNC: 9376
• e!Ensembl: ENSG00000132356

Protein

• UniProt ID: Q13131
• Protein name: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (AMPK subunit alpha-1) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (EC 2.7.11.27) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) (Tau-protein kinase PRKAA1) (EC 2.7.11.26)
• Protein function: Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. 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. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. 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. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. 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. 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. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. 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. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In that process also activates WDR45 (PubMed:28561066). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. 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. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.
• PDB: 4RED, 4RER, 4REW, 5EZV, 6C9F, 6C9G, 6C9H, 6C9J
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	27 → 279	Protein kinase domain	Domain
  PF16579	AdenylateSensor	406 → 503	Adenylate sensor of SNF1-like protein kinase	Domain

• Sequence:

  MRRLSSWRKMATAEKQKHDGRVKIGHYILGDTLGVGTFGKVKVGKHELTGHKVAVKILNR
  QKIRSLDVVGKIRREIQNLKLFRHPHIIKLYQVISTPSDIFMVMEYVSGGELFDYICKNG
  RLDEKESRRLFQQILSGVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEF
  LRTSCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDDHVPTLFKKICDG
  IFYTPQYLNPSVISLLKHMLQVDPMKRATIKDIREHEWFKQDLPKYLFPEDPSYSSTMID
  DEALKEVCEKFECSEEEVLSCLYNRNHQDPLAVAYHLIIDNRRIMNEAKDFYLATSPPDS
  FLDDHHLTRPHPERVPFLVAETPRARHTLDELNPQKSKHQGVRKAKWHLGIRSQSRPNDI
  MAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTYSKMSLQLYQVDSRTYLLDFRSIDDE
  ITEAKSGTATPQRSGSVSNYRSCQRSDSDAEAQGKSSEVSLTSSVTSLDSSPVDLTPRPG
  SHTIEFFEMCANLIKILAQ

• Sequence length: 559