LMPD Database

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LMP001563

UniProt Annotations

Entry Information
Gene Namepyruvate dehydrogenase kinase, isoenzyme 4
Protein EntryPDK4_MOUSE
UniProt IDO70571
SpeciesMouse
Comments
Comment typeDescription
Catalytic ActivityATP + [pyruvate dehydrogenase (acetyl- transferring)] = ADP + [pyruvate dehydrogenase (acetyl- transferring)] phosphate.
Disruption PhenotypeNo visible phenotype at birth. Mice have lower blood glucose and pyruvate levels after overnight fasting than normal, while the levels of ketone bodies are increased. After 48 h starving, their rate of glucose oxidation is increased, and glycolysis decreased, compared to wild type mice. Likewise, their rate of fatty acid oxidation is lower than normal in response to starvation. In contrast, there are no differences in blood glucose levels betwen fed mutant and wild type mice. In response to a high-fat diet, mutant mice have lower de novo fatty acid biosynthesis, and lower liver steatosis than wild-type. Mutant mice show normal bone formation and normal bone metabolism, excepting reduced bone loss when suspended to induce disuse osteoporosis. {ECO:0000269|PubMed:16606348, ECO:0000269|PubMed:18430968, ECO:0000269|PubMed:19627255, ECO:0000269|PubMed:21803180, ECO:0000269|PubMed:22360721, ECO:0000269|PubMed:22436846}.
FunctionKinase that plays a key role in 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 in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. 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. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism. {ECO:0000269|PubMed:16606348, ECO:0000269|PubMed:18083902, ECO:0000269|PubMed:18430968, ECO:0000269|PubMed:19627255, ECO:0000269|PubMed:21321124, ECO:0000269|PubMed:22360721}.
InductionUp-regulated by PPARD. {ECO:0000269|PubMed:17669420}.
SimilarityBelongs to the PDK/BCKDK protein kinase family. {ECO:0000305}.
SimilarityContains 1 histidine kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00107}.
Subcellular LocationMitochondrion matrix {ECO:0000250}.
SubunitHomodimer. 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) (By similarity). {ECO:0000250}.