PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2)

Gene

• Entrez ID: 5563
• Gene name: Protein kinase AMP-activated catalytic subunit alpha 2
• Gene symbol: PRKAA2
• Synonyms: AMPK, AMPK2, AMPKa2, PRKAA
• Chromosome: 1
• Chromosome location: 1p32.2
• Summary: 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]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT026874	hsa-miR-192-5p	Microarray	19074876
MIRT027841	hsa-miR-98-5p	Microarray	19088304
MIRT047217	hsa-miR-182-5p	CLASH	23622248
MIRT052107	hsa-let-7b-5p	CLASH	23622248
MIRT281965	hsa-miR-4720-3p	PAR-CLIP	21572407
MIRT281967	hsa-miR-4804-3p	PAR-CLIP	21572407
MIRT449652	hsa-miR-510-3p	PAR-CLIP	22100165
MIRT449653	hsa-miR-578	PAR-CLIP	22100165
MIRT449654	hsa-miR-526b-5p	PAR-CLIP	22100165
MIRT449655	hsa-miR-664b-3p	PAR-CLIP	22100165
MIRT449656	hsa-miR-579-3p	PAR-CLIP	22100165
MIRT449657	hsa-miR-6853-3p	PAR-CLIP	22100165
MIRT449658	hsa-miR-5696	PAR-CLIP	22100165
MIRT449658	hsa-miR-5696	HITS-CLIP	23824327
MIRT449659	hsa-miR-1206	PAR-CLIP	22100165
MIRT449660	hsa-miR-4635	PAR-CLIP	22100165
MIRT449661	hsa-miR-26b-3p	PAR-CLIP	22100165
MIRT449662	hsa-miR-153-5p	PAR-CLIP	22100165
MIRT449663	hsa-miR-1250-3p	PAR-CLIP	22100165
MIRT555220	hsa-miR-7844-5p	PAR-CLIP	21572407
MIRT654768	hsa-miR-302c-5p	HITS-CLIP	23824327
MIRT654769	hsa-miR-3667-3p	HITS-CLIP	23824327
MIRT654770	hsa-miR-6734-3p	HITS-CLIP	23824327
MIRT654771	hsa-miR-4729	HITS-CLIP	23824327
MIRT654772	hsa-miR-4719	HITS-CLIP	23824327
MIRT654773	hsa-miR-382-3p	HITS-CLIP	23824327
MIRT654774	hsa-miR-500a-5p	HITS-CLIP	23824327
MIRT654775	hsa-miR-200a-3p	HITS-CLIP	23824327
MIRT654776	hsa-miR-141-3p	HITS-CLIP	23824327
MIRT700613	hsa-miR-3658	HITS-CLIP	23313552
MIRT700614	hsa-miR-3678-3p	HITS-CLIP	23313552
MIRT700615	hsa-miR-1273h-3p	HITS-CLIP	23313552
MIRT700616	hsa-miR-7154-5p	HITS-CLIP	23313552
MIRT700617	hsa-miR-3653-3p	HITS-CLIP	23313552
MIRT700618	hsa-miR-4771	HITS-CLIP	23313552
MIRT700619	hsa-miR-3166	HITS-CLIP	23313552
MIRT700620	hsa-miR-494-3p	HITS-CLIP	23313552
MIRT700621	hsa-miR-8060	HITS-CLIP	23313552
MIRT700622	hsa-miR-4761-5p	HITS-CLIP	23313552
MIRT700623	hsa-miR-495-5p	HITS-CLIP	23313552
MIRT731819	hsa-miR-27a-3p	Luciferase reporter assay, Western blot	27779715

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003682	Function	Chromatin binding	ISS
GO:0004672	Function	Protein kinase activity	TAS	7959015
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	ISS
GO:0004679	Function	AMP-activated protein kinase activity	IDA	18439900
GO:0004679	Function	AMP-activated protein kinase activity	ISS
GO:0004712	Function	Protein serine/threonine/tyrosine kinase activity	IDA	22797923
GO:0005515	Function	Protein binding	IPI	18439900, 19274086, 20562859, 20801214, 21072212, 21516116, 24722188, 25241761, 25416956, 28514442, 28561066, 29892012, 30886144, 31515488, 32296183, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	TAS	21768291
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005794	Component	Golgi apparatus	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006468	Process	Protein phosphorylation	IBA	21873635
GO:0006633	Process	Fatty acid biosynthetic process	IEA
GO:0006695	Process	Cholesterol biosynthetic process	IEA
GO:0006853	Process	Carnitine shuttle	TAS
GO:0007050	Process	Cell cycle arrest	TAS
GO:0007165	Process	Signal transduction	TAS	7959015
GO:0008610	Process	Lipid biosynthetic process	ISS
GO:0010494	Component	Cytoplasmic stress granule	ISS
GO:0010508	Process	Positive regulation of autophagy	ISS
GO:0010629	Process	Negative regulation of gene expression	ISS
GO:0014850	Process	Response to muscle activity	IEA
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0016236	Process	Macroautophagy	TAS
GO:0016239	Process	Positive regulation of macroautophagy	TAS	25126726
GO:0016241	Process	Regulation of macroautophagy	ISS
GO:0016241	Process	Regulation of macroautophagy	TAS
GO:0016607	Component	Nuclear speck	IDA
GO:0030424	Component	Axon	ISS
GO:0030425	Component	Dendrite	ISS
GO:0031669	Process	Cellular response to nutrient levels	ISS
GO:0032007	Process	Negative regulation of TOR signaling	ISS
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:0042149	Process	Cellular response to glucose starvation	ISS
GO:0042304	Process	Regulation of fatty acid biosynthetic process	TAS
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:0045821	Process	Positive regulation of glycolytic process	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0047322	Function	[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity	IEA
GO:0048511	Process	Rhythmic process	IEA
GO:0050405	Function	[acetyl-CoA carboxylase] kinase activity	IEA
GO:0055089	Process	Fatty acid homeostasis	ISS
GO:0062028	Process	Regulation of stress granule assembly	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:0071380	Process	Cellular response to prostaglandin E stimulus	IEA
GO:0097009	Process	Energy homeostasis	ISS
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0106311	Function	Protein threonine kinase activity	IEA
GO:1901796	Process	Regulation of signal transduction by p53 class mediator	TAS
GO:1903829	Process	Positive regulation of cellular protein localization	ISS
GO:1904428	Process	Negative regulation of tubulin deacetylation	ISS
GO:2000758	Process	Positive regulation of peptidyl-lysine acetylation	ISS

Other IDs

• MIM: 600497
• HGNC: 9377
• e!Ensembl: ENSG00000162409

Protein

• UniProt ID: P54646
• Protein name: 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK subunit alpha-2) (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)
• 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. 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. 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). 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 phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. 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. Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity).
• PDB: 2H6D, 2LTU, 2YZA, 3AQV, 4CFE, 4CFF, 4ZHX, 5EZV, 5ISO, 6B1U, 6B2E, 6BX6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	16 → 268	Protein kinase domain	Domain
  PF16579	AdenylateSensor	401 → 495	Adenylate sensor of SNF1-like protein kinase	Domain

• Sequence:

  MAEKQKHDGRVKIGHYVLGDTLGVGTFGKVKIGEHQLTGHKVAVKILNRQKIRSLDVVGK
  IKREIQNLKLFRHPHIIKLYQVISTPTDFFMVMEYVSGGELFDYICKHGRVEEMEARRLF
  QQILSAVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYA
  APEVISGRLYAGPEVDIWSCGVILYALLCGTLPFDDEHVPTLFKKIRGGVFYIPEYLNRS
  VATLLMHMLQVDPLKRATIKDIREHEWFKQDLPSYLFPEDPSYDANVIDDEAVKEVCEKF
  ECTESEVMNSLYSGDPQDQLAVAYHLIIDNRRIMNQASEFYLASSPPSGSFMDDSAMHIP
  PGLKPHPERMPPLIADSPKARCPLDALNTTKPKSLAVKKAKWHLGIRSQSKPYDIMAEVY
  RAMKQLDFEWKVVNAYHLRVRRKNPVTGNYVKMSLQLYLVDNRSYLLDFKSIDDEVVEQR
  SGSSTPQRSCSAAGLHRPRSSFDSTTAESHSLSGSLTGSLTGSTLSSVSPRLGSHTMDFF
  EMCASLITTLAR

• Sequence length: 552