PRKAG3 (protein kinase AMP-activated non-catalytic subunit gamma 3)

Gene

• Entrez ID: 53632
• Gene name: Protein kinase AMP-activated non-catalytic subunit gamma 3
• Gene symbol: PRKAG3
• Synonyms: AMPKG3, SMGMQTL
• Chromosome: 2
• Chromosome location: 2q35
• Summary: The protein encoded by this gene is a regulatory 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. This subunit is one of the gamma regulatory subunits of AMPK. It is dominantly expressed in skeletal muscle. Studies of the pig counterpart suggest that this subunit may play a key role in the regulation of energy metabolism in skeletal muscle. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs138130157	G>A	Pathogenic	Coding sequence variant, missense variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	28514442, 32296183
GO:0005524	Function	ATP binding	IEA
GO:0005615	Component	Extracellular space	HDA	22664934
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0005978	Process	Glycogen biosynthetic process	IEA
GO:0006096	Process	Glycolytic process	IEA
GO:0006468	Process	Protein phosphorylation	IBA	21873635
GO:0006633	Process	Fatty acid biosynthetic process	IEA
GO:0007050	Process	Cell cycle arrest	TAS
GO:0014873	Process	Response to muscle activity involved in regulation of muscle adaptation	IEA
GO:0016208	Function	AMP binding	IBA	21873635
GO:0016236	Process	Macroautophagy	TAS
GO:0016241	Process	Regulation of macroautophagy	TAS
GO:0019887	Function	Protein kinase regulator activity	IBA	21873635
GO:0019901	Function	Protein kinase binding	IBA	21873635
GO:0019901	Function	Protein kinase binding	IDA	10698692
GO:0031588	Component	Nucleotide-activated protein kinase complex	IBA	21873635
GO:0035556	Process	Intracellular signal transduction	TAS	10698692
GO:0042149	Process	Cellular response to glucose starvation	IBA	21873635
GO:0050790	Process	Regulation of catalytic activity	IBA	21873635
GO:0071900	Process	Regulation of protein serine/threonine kinase activity	IEA
GO:1901796	Process	Regulation of signal transduction by p53 class mediator	TAS

Other IDs

• MIM: 604976
• HGNC: 9387
• e!Ensembl: ENSG00000115592

Protein

• UniProt ID: Q9UGI9
• Protein name: 5'-AMP-activated protein kinase subunit gamma-3 (AMPK gamma3) (AMPK subunit gamma-3)
• Protein function: AMP/ATP-binding 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. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00571	CBS	273 → 333	CBS domain	Domain
  PF00571	CBS	352 → 406	CBS domain	Domain
  PF00571	CBS	417 → 479	CBS domain	Domain

• Sequence:

  MEPGLEHALRRTPSWSSLGGSEHQEMSFLEQENSSSWPSPAVTSSSERIRGKRRAKALRW
  TRQKSVEEGEPPGQGEGPRSRPAAESTGLEATFPKTTPLAQADPAGVGTPPTGWDCLPSD
  CTASAAGSSTDDVELATEFPATEAWECELEGLLEERPALCLSPQAPFPKLGWDDELRKPG
  AQIYMRFMQEHTCYDAMATSSKLVIFDTMLEIKKAFFALVANGVRAAPLWDSKKQSFVGM
  LTITDFILVLHRYYRSPLVQIYEIEQHKIETWREIYLQGCFKPLVSISPNDSLFEAVYTL
  IKNRIHRLPVLDPVSGNVLHILTHKRLLKFLHIFGSLLPRPSFLYRTIQDLGIGTFRDLA
  VVLETAPILTALDIFVDRRVSALPVVNECGQVVGLYSRFDVIHLAAQQTYNHLDMSVGEA
  LRQRTLCLEGVLSCQPHESLGEVIDRIAREQVHRLVLVDETQHLLGVVSLSDILQALVLS
  PAGIDALGA

• Sequence length: 489