Protein: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 4) (O54937)
Organism: Rattus norvegicus (Rat)
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.
Subcellular location: Mitochondrion matrix.
Sequence: MKAARFVMRSASSLGNAGLVPREVELFSRYSPSPLSMKQLLDFGSENACERTSFSFLRQELPVRLANILKEIDILPEHLVNTPSVQLVKSWYIQSLMDLVEFHEKSPEDQKVLSDFVDTLVKVRNRHHNVVPTMAQGILEYKDNCTVDPVTNQNLQYFLDRFYMNRISTRMLMNQHILIFSDSKTGNPSHIGSIDPNCDVVAVVEDAFECAKMLCDQYYLTSPELKLTQVNGKFPGQPIHIVYVPSHLHHMLFELFKNAMRATVEHQENRPFLTPVEATVVLGKEDLTIKISDRGGGVPLRITDRLFSYTYSTAPTPVMDNSRNAPLAGFGYGLPISRLYAKYFQGDLNLYSMSGYGTDAIIYLKALSSESIEKLPVFNKSAFKHYQMSSEADDWCIPSKEPKNLSKEKLAV
InterPro domains: - IPR036890: Histidine kinase/HSP90-like ATPase superfamily (homologous_superfamily) [191-376]
- IPR003594: Histidine kinase/HSP90-like ATPase domain (domain) [243-368]
- IPR018955: Branched-chain alpha-ketoacid dehydrogenase kinase/Pyruvate dehydrogenase kinase, N-terminal (domain) [34-195]
- IPR039028: PDK/BCKDK protein kinase (family) [20-376]
- IPR005467: Histidine kinase domain (domain) [245-368]
- IPR036784: Alpha-ketoacid/pyruvate dehydrogenase kinase, N-terminal domain superfamily (homologous_superfamily) [18-189]
Interaction partners: - Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
- Ac1164
- Solute carrier family 2, facilitated glucose transporter member 4
- Stress-70 protein, mitochondrial
- Angiopoietin-related protein 4
- Peroxisome proliferator-activated receptor alpha
- Peroxisome proliferator-activated receptor gamma coactivator 1-alpha
- Carnitine O-palmitoyltransferase 1, muscle isoform
- Putative mitochondrial transporter UCP3
- Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0004672 (protein kinase activity), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0004712 (protein serine/threonine/tyrosine kinase activity), GO:0016301 (kinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0044237 (cellular metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0019538 (protein metabolic process), GO:0043170 (macromolecule metabolic process), GO:0006793 (phosphorus metabolic process), GO:0036211 (protein modification process), GO:0006796 (phosphate-containing compound metabolic process), GO:0043412 (macromolecule modification), GO:0006468 (protein phosphorylation), GO:0018193 (peptidyl-amino acid modification), GO:0016310 (phosphorylation), GO:0018105 (peptidyl-serine phosphorylation), GO:0018209 (peptidyl-serine modification)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0032991 (protein-containing complex), GO:1902494 (catalytic complex), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:1990204 (oxidoreductase complex), GO:0005739 (mitochondrion), GO:0043227 (membrane-bounded organelle), GO:0045254 (pyruvate dehydrogenase complex), GO:0043231 (intracellular membrane-bounded organelle)