Protein: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 1) (PDH kinase 1) (Q8BFP9)
Organism: Mus musculus (Mouse)
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. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress (By similarity).
Subcellular location: Mitochondrion matrix {ECO:0000250}.
Sequence: MRLARLLRGGTSVRPLCAVPCASRSLASASASGSGPASELGVPGQVDFYARFSPSPLSMKQFLDFGSVNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQELLDFKDKSAEDAKTIYEFTDTVIRIRNRHNDVIPTMAQGVTEYKESFGVDPVTSQNVQYFLDRFYMSRISIRMLLNQHSLLFGGKGSPSHRKHIGSINPNCDVVEVIKDGYENARRLCDLYYVNSPELELEELNAKSPGQTIQVVYVPSHLYHMVFELFKNAMRATMEHHADKGVYPPIQVHVTLGEEDLTVKMSDRGGGVPLRKIDRLFNYMYSTAPRPRVETSRAVPLAGFGYGLPISRLYAQYFQGDLKLYSLEGYGTDAVIYIKALSTESVERLPVYNKAAWKHYKANHEADDWCVPSREPKDMTTFRSS
InterPro domains: - IPR036890: Histidine kinase/HSP90-like ATPase superfamily (homologous_superfamily) [213-399]
- IPR003594: Histidine kinase/HSP90-like ATPase domain (domain) [266-391]
- IPR018955: Branched-chain alpha-ketoacid dehydrogenase kinase/Pyruvate dehydrogenase kinase, N-terminal (domain) [56-218]
- IPR039028: PDK/BCKDK protein kinase (family) [42-400]
- IPR005467: Histidine kinase domain (domain) [268-391]
- IPR036784: Alpha-ketoacid/pyruvate dehydrogenase kinase, N-terminal domain superfamily (homologous_superfamily) [31-212]
Interaction partners: - [Pyruvate dehydrogenase
- Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
- Pyruvate dehydrogenase E1 component subunit beta, mitochondrial
- Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial
- Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
- Pyruvate dehydrogenase protein X component, mitochondrial
- Dihydrolipoyl dehydrogenase, 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:0050789 (regulation of biological process), GO:0042592 (homeostatic process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0009605 (response to external stimulus), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0051239 (regulation of multicellular organismal process), GO:0048878 (chemical homeostasis), GO:0009719 (response to endogenous stimulus), GO:0006885 (regulation of pH), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0050801 (monoatomic ion homeostasis), GO:0034103 (regulation of tissue remodeling), GO:0033500 (carbohydrate homeostasis), GO:0071495 (cellular response to endogenous stimulus), GO:1901700 (response to oxygen-containing compound), GO:0010033 (response to organic substance), GO:0009725 (response to hormone), GO:0009991 (response to extracellular stimulus), GO:0042594 (response to starvation), GO:1901698 (response to nitrogen compound), GO:0070887 (cellular response to chemical stimulus), GO:0009889 (regulation of biosynthetic process), GO:0062012 (regulation of small molecule metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0007166 (cell surface receptor signaling pathway), GO:0080090 (regulation of primary metabolic process), GO:1901652 (response to peptide), GO:0071417 (cellular response to organonitrogen compound), GO:0010565 (regulation of cellular ketone metabolic process), GO:0007167 (enzyme-linked receptor protein signaling pathway), GO:0071310 (cellular response to organic substance), GO:0010675 (regulation of cellular carbohydrate metabolic process), GO:0010906 (regulation of glucose metabolic process), GO:1901699 (cellular response to nitrogen compound), GO:0042762 (regulation of sulfur metabolic process), GO:0006109 (regulation of carbohydrate metabolic process), GO:0046890 (regulation of lipid biosynthetic process), GO:0043434 (response to peptide hormone), GO:0006140 (regulation of nucleotide metabolic process), GO:0032870 (cellular response to hormone stimulus), GO:0034248 (regulation of amide metabolic process), GO:0010243 (response to organonitrogen compound), GO:0055080 (monoatomic cation homeostasis), GO:0031667 (response to nutrient levels), GO:0042593 (glucose homeostasis), GO:0031326 (regulation of cellular biosynthetic process), GO:0046850 (regulation of bone remodeling), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0019216 (regulation of lipid metabolic process), GO:1901701 (cellular response to oxygen-containing compound), GO:0051174 (regulation of phosphorus metabolic process), GO:1900542 (regulation of purine nucleotide metabolic process), GO:0071375 (cellular response to peptide hormone stimulus), GO:0032868 (response to insulin), GO:0042304 (regulation of fatty acid biosynthetic process), GO:0019220 (regulation of phosphate metabolic process), GO:0045124 (regulation of bone resorption), GO:1901653 (cellular response to peptide), GO:0007169 (transmembrane receptor protein tyrosine kinase signaling pathway), GO:0030808 (regulation of nucleotide biosynthetic process), GO:0019217 (regulation of fatty acid metabolic process), GO:1900371 (regulation of purine nucleotide biosynthetic process), GO:0008286 (insulin receptor signaling pathway), GO:0032869 (cellular response to insulin stimulus), GO:0046320 (regulation of fatty acid oxidation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031975 (envelope), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0031090 (organelle membrane), GO:0031967 (organelle envelope), GO:0005739 (mitochondrion), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005740 (mitochondrial envelope), GO:0019866 (organelle inner membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0031966 (mitochondrial membrane), GO:0005743 (mitochondrial inner membrane)