5'-AMP-activated protein kinase subunit gamma-2

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.

Classification

Family (Pfam)

PF00571 CBS

InterPro

AMPK_gamma/SDS23_families, CBS_dom, CBS_dom_sf

Functional cluster

RRM RNA-Binding & Protein Kinases

Gene Ontology · 29

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005788 endoplasmic reticulum lumen
• GO:0005615 extracellular space
• GO:0005654 nucleoplasm
• GO:0031588 nucleotide-activated protein kinase complex
• GO:0005634 nucleus
• GO:0043531 ADP binding
• GO:0016208 AMP binding
• GO:0004679 AMP-activated protein kinase activity
• GO:0005524 ATP binding
• GO:0004862 cAMP-dependent protein kinase inhibitor activity
• GO:0008603 cAMP-dependent protein kinase regulator activity
• GO:0008607 phosphorylase kinase regulator activity
• GO:0030295 protein kinase activator activity
• GO:0019901 protein kinase binding
• GO:0019887 protein kinase regulator activity
• GO:0006754 ATP biosynthetic process
• GO:0042149 cellular response to glucose starvation
• GO:0006633 fatty acid biosynthetic process
• GO:0005977 glycogen metabolic process
• GO:0035556 intracellular signal transduction
• GO:0045722 positive regulation of gluconeogenesis
• GO:0051726 regulation of cell cycle
• GO:0046324 regulation of D-glucose import across plasma membrane
• GO:0019217 regulation of fatty acid metabolic process
• GO:0046320 regulation of fatty acid oxidation
• GO:0006110 regulation of glycolytic process
• GO:0016126 sterol biosynthetic process

Disease associations

• Wolff-Parkinson-White syndrome MONDO:0008685
• lethal congenital glycogen storage disease of heart MONDO:0009867
• hypertrophic cardiomyopathy 6 MONDO:0010946

Drugs targeting this protein · 1

• ACADESINE activator

Related proteins · sequence + function similarity

• 5'-AMP-activated protein kinase subunit gamma-2 0.98
• 5'-AMP-activated protein kinase subunit gamma-2 0.97
• Protein sds23/moc1 0.77
• 5'-AMP-activated protein kinase subunit gamma-1 0.74
• Protein SDS23 0.73
• 5'-AMP-activated protein kinase subunit gamma-1 0.73
• Protein SDS23 0.73
• 5'-AMP-activated protein kinase subunit gamma-1 0.73
• 5'-AMP-activated protein kinase subunit gamma-1 0.73
• 5'-AMP-activated protein kinase subunit gamma-1 0.73
• Protein SDS23 0.71
• Protein SDS23 0.69

Co-cited proteins · studied together in the literature

• Serine/threonine-protein kinase TNNI3K 1 shared papers
• 5'-AMP-activated protein kinase subunit gamma-3 7 shared papers
• 5'-AMP-activated protein kinase subunit gamma-1 6 shared papers
• 5'-AMP-activated protein kinase subunit beta-2 3 shared papers
• 5'-AMP-activated protein kinase subunit beta-1 3 shared papers
• 5'-AMP-activated protein kinase catalytic subunit alpha-1 4 shared papers
• Protein O-GlcNAcase 1 shared papers
• 5'-AMP-activated protein kinase catalytic subunit alpha-2 3 shared papers
• UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit 1 shared papers
• 5'-AMP-activated protein kinase subunit beta-2 1 shared papers
• 5'-AMP-activated protein kinase subunit beta-2 1 shared papers
• 5'-AMP-activated protein kinase subunit gamma-1 1 shared papers

Literature · 21 cited papers

• Reduced kinase function in two ultra-rare TNNI3K variants in families with congenital junctional ectopic tachycardia. Clin. Genet. · 2024
• Cross-talk between two essential nutrient-sensitive enzymes: O-GlcNAc transferase (OGT) and AMP-activated protein kinase (AMPK). J. Biol. Chem. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop. Autophagy · 2011
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
• AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat. Rev. Mol. Cell Biol. · 2007
• AMP-activated protein kinase in metabolic control and insulin signaling. Circ. Res. · 2007
• Regulation of AMP-activated protein kinase by a pseudosubstrate sequence on the gamma subunit. EMBO J. · 2007
• Fatal congenital heart glycogenosis caused by a recurrent activating R531Q mutation in the gamma 2-subunit of AMP-activated protein kinase (PRKAG2), not by phosphorylase kinase deficiency. Am. J. Hum. Genet. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• … and 9 more in the literature graph