Tchem PDK4 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial

Protein Summary

Description

Kinase 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. This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitrochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, thereby contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q16654

Gene Name

• PDK4

Ensembl ID

• ENST00000005178
• ENSP00000005178
• ENSG00000004799

Symbol

• PDHK4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
gene perturbation	0.92
PubMedID	0.91
molecular function	0.9
small molecule perturbation	0.8
biological process	0.77

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / [Pyruvate Dehydrogenase (Acetyl-transferring)] Kinase Isozyme 4, Mitochondrial

DTO Classes

Protein / Kinase / Protein Kinase / Atypical Group / Pdhk Family / [Pyruvate Dehydrogenase (Acetyl-transferring)] Kinase Isozyme 4, Mitochondrial

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 413.18   (req: < 5)

Gene RIFs: 73   (req: <= 3)

Antibodies: 586   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 413.18   (req: >= 5)

Gene RIFs: 73   (req: > 3)

Antibodies: 586   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 6

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0