Names & Taxonomy

Uniprot ID:
Q15119
Entry Name:
PDK2_HUMAN
Status:
reviewed
Protein Names:
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 2) (PDH kinase 2) (PDKII)
Gene Names:
PDK2 PDHK2
Gene Names Primary:
PDK2
Organism:
Homo sapiens (Human)

Structure

Length:
407
Sequence:
MRWVWALLKNASLAGAPKYIEHFSKFSPSPLSMKQFLDFGSSNACEKTSFTFLRQELPVRLANIMKEINLLPDRVLSTPSVQLVQSWYVQSLLDIMEFLDKDPEDHRTLSQFTDALVTIRNRHNDVVPTMAQGVLEYKDTYGDDPVSNQNIQYFLDRFYLSRISIRMLINQHTLIFDGSTNPAHPKHIGSIDPNCNVSEVVKDAYDMAKLLCDKYYMASPDLEIQEINAANSKQPIHMVYVPSHLYHMLFELFKNAMRATVESHESSLILPPIKVMVALGEEDLSIKMSDRGGGVPLRKIERLFSYMYSTAPTPQPGTGGTPLAGFGYGLPISRLYAKYFQGDLQLFSMEGFGTDAVIYLKALSTDSVERLPVYNKSAWRHYQTIQEAGDWCVPSTEPKNTSTYRVS
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Mitochondrion matrix.

Function

Function:
Kinase 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.
Catalytic Activity:
ATP + = ADP + phosphate.
Enzyme Regulation:
ENZYME REGULATION: Activity is enhanced by binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by ADP and pyruvate; these compounds interfere with DLAT binding and thereby inhibit kinase activity. Inhibited by dichloroacetate. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity.
Gene Ontology Go:
cytoplasm
mitochondrial matrix
mitochondrial pyruvate dehydrogenase complex
mitochondrion
nucleoplasm
ATP binding
protein homodimerization activity
protein kinase activity
pyruvate dehydrogenase (acetyl-transferring) kinase activity
cellular metabolic process
cellular response to nutrient
cellular response to reactive oxygen species
glucose homeostasis
glucose metabolic process
insulin receptor signaling pathway
intrinsic apoptotic signaling pathway by p53 class mediator
protein phosphorylation
pyruvate metabolic process
regulation of acetyl-CoA biosynthetic process from pyruvate
regulation of cellular ketone metabolic process
regulation of gluconeogenesis
regulation of glucose metabolic process
regulation of pH
small molecule metabolic process
Gene Ontology Biological Process:
cellular metabolic process
cellular response to nutrient
cellular response to reactive oxygen species
glucose homeostasis
glucose metabolic process
insulin receptor signaling pathway
intrinsic apoptotic signaling pathway by p53 class mediator
protein phosphorylation
pyruvate metabolic process
regulation of acetyl-CoA biosynthetic process from pyruvate
regulation of cellular ketone metabolic process
regulation of gluconeogenesis
regulation of glucose metabolic process
regulation of pH
small molecule metabolic process
Gene Ontology Molecular Function:
ATP binding
protein homodimerization activity
protein kinase activity
pyruvate dehydrogenase (acetyl-transferring) kinase activity
Gene Ontology Cellular Component:
cytoplasm
mitochondrial matrix
mitochondrial pyruvate dehydrogenase complex
mitochondrion
nucleoplasm
Keywords:
3D-structure
ATP-binding
Alternative splicing
Carbohydrate metabolism
Complete proteome
Glucose metabolism
Kinase
Mitochondrion
Nucleotide-binding
Polymorphism
Reference proteome
Transferase
Transit peptide

Publication

PubMed ID:
7499431 14702039 16625196 15489334 9787110 12816949 15491150 16517984 17222789 17669420 19833728 21283817 22123926 24275569 16401071 17344846