lmmol · Proteins

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

UniProt Q16654 Organism Homo sapiens Gene PDHK4, PDK4 EC 2.7.11.2

Also known as: PDHK4, PDK4

Function

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.

Classification

Family (Pfam)
PF10436 BCDHK_Adom3, PF02518 HATPase_c
InterPro
AK/P_DHK_N_sf, BCDHK/PDK_N, BCKD/PDK, HATPase_C_sf, HATPase_dom, His_kinase_dom
Functional cluster
Tubulins & Mitochondrial Metabolic Enzymes

Experimental structures · PDB · 8

A predicted model is available from AlphaFold.

Gene Ontology · 17

Drugs targeting this protein · 1

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 12 cited papers

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