[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial

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.

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 · 5

• 2Q8F X-ray 2.03A
• 2Q8G X-ray 1.90A
• 2Q8H X-ray 2.00A
• 9M3O X-ray 1.76A
• 9M3P X-ray 2.01A

A predicted model is available from AlphaFold.

Gene Ontology · 14

• GO:0005759 mitochondrial matrix
• GO:0005739 mitochondrion
• GO:0005886 plasma membrane
• GO:0045254 pyruvate dehydrogenase complex
• GO:0005524 ATP binding
• GO:0004672 protein kinase activity
• GO:0004740 pyruvate dehydrogenase (acetyl-transferring) kinase activity
• GO:0008283 cell population proliferation
• GO:0006006 glucose metabolic process
• GO:0097411 hypoxia-inducible factor-1alpha signaling pathway
• GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress
• GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0010906 regulation of glucose metabolic process
• GO:0010510 regulation of pyruvate decarboxylation to acetyl-CoA

Drugs targeting this protein · 1

• SODIUM DICHLOROACETATE inhibitor

Related proteins · sequence + function similarity

• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial 0.97
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial 0.97
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial 0.91
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial 0.90
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial 0.90
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase, mitochondrial 0.90
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial 0.89
• Probable [pyruvate dehydrogenase (acetyl-transferring)] kinase, mitochondrial 0.89
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial 0.89
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial 0.89
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial 0.89
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial 0.89

Co-cited proteins · studied together in the literature

• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial 1 shared papers
• [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial 2 shared papers
• Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial 1 shared papers
• Phosphoglycerate kinase 1 1 shared papers
• Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 1 shared papers
• Mitogen-activated protein kinase 1 1 shared papers

Literature · 13 cited papers

• Mitochondrial Akt regulation of hypoxic tumor reprogramming. Cancer Cell · 2016
• Mitochondria-Translocated PGK1 Functions as a Protein Kinase to Coordinate Glycolysis and the TCA Cycle in Tumorigenesis. Mol. Cell · 2016
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism. Mol. Cell · 2011
• Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer. Am. J. Pathol. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Pyruvate dehydrogenase complex activity controls metabolic and malignant phenotype in cancer cells. J. Biol. Chem. · 2008
• Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Structure · 2007
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• … and 1 more in the literature graph