LMPD Database

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LMP012832

UniProt Annotations

Entry Information
Gene Namepyruvate dehydrogenase kinase, isozyme 4
Protein EntryPDK4_RAT
UniProt IDO54937
SpeciesRat
Comments
Comment typeDescription
Catalytic ActivityATP + [pyruvate dehydrogenase (acetyl- transferring)] = ADP + [pyruvate dehydrogenase (acetyl- transferring)] phosphate. {ECO:0000269|PubMed:11486000, ECO:0000269|PubMed:9405293}.
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
InductionUp-regulated by exercise, starvation, glucocorticoids, thyroid hormone and epinephrine. Down-regulated by insulin. {ECO:0000269|PubMed:19703515, ECO:0000269|PubMed:19948729, ECO:0000269|PubMed:20739620}.
SimilarityBelongs to the PDK/BCKDK protein kinase family
SimilarityContains 1 histidine kinase domain
Subcellular LocationMitochondrion matrix.
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)
Tissue SpecificityUbiquitous; highest levels of expression in heart and skeletal muscle