LMPD Database

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LMP001796

UniProt Annotations

Entry Information
Gene Namepyruvate dehydrogenase kinase, isoenzyme 2
Protein EntryPDK2_MOUSE
UniProt IDQ9JK42
SpeciesMouse
Comments
Comment typeDescription
Catalytic ActivityATP + [pyruvate dehydrogenase (acetyl- transferring)] = ADP + [pyruvate dehydrogenase (acetyl- transferring)] phosphate.
Disruption PhenotypeNo visible phenotype, due to the fact that PDK2-deficient mice have increased PDK1 levels (PubMed:21411764). Mice have lower blood glucose levels in the fed state, but not after fasting. Likewise, they display increased pyruvate dehydrogenase activity in liver and skeletal muscle in the fed state, but not after fasting. Fasting mice lacking both PDK2 and PDK4 show strongly decreased blood glucose levels, increased circulating ketone body levels leading to ketoacidosis with dangerously low blood pH levels, hypothermia, and ultimately death (PubMed:22360721). {ECO:0000269|PubMed:21411764, ECO:0000269|PubMed:22360721}.
FunctionKinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis. {ECO:0000269|PubMed:22360721}.
InductionUp-regulated by glucose and palmitic acid. Up-regulated by PPARD. {ECO:0000269|PubMed:16631612, ECO:0000269|PubMed:17669420}.
InteractionO08908:Pik3r2; NbExp=3; IntAct=EBI-643530, EBI-643570;
SimilarityBelongs to the PDK/BCKDK protein kinase family. {ECO:0000305}.
SimilarityContains 1 histidine kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00107}.
Subcellular LocationMitochondrion matrix {ECO:0000269|PubMed:21190881}.
SubunitHomodimer, and heterodimer with PDK1. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). {ECO:0000269|PubMed:21190881}.
Tissue SpecificityDetected in heart (at protein level). {ECO:0000269|PubMed:21190881}.