PDHK2 an atypical protein kinase associated with the mitochondrial matrix. The PDHKs play crucial roles in switching metabolic flux from oxidative phosphorylation towards glycolysis. PDHK2 is expressed in all tissues. Contains a HATPase_c catalytic domain, found in several ATP-binding proteins including protein histidine kinases (PHKs), PHDKs, DNA gyrase B, topoisomerases, heat shock proteins, and DNA mismatch repair proteins. PDHK regulates glucose oxidation through inhibitory phosphorylation of the E1 alpha subunit of the mitochondrial pyruvate dehydrogenase complex (PDHC) at any one of 3 inhibitory serine residues. Inhibitory sites 1, 2, and 3 correspond to S293, S300, and S232 in human PDHA1, respectively. Four PDHK isoenzymes have been described, each with different site specificity: all four phosphorylate sites 1 and 2 but at different rates; for site 1 PDHK2 >PDHK4 >PDHK1 >PDHK3; for site 2, PDHK3> PDHK4 > PDHK2 > PDHK1. Only PDHK1 phosphorylates site 3. PDHKs are recruited to the PDHC by binding to a lipoyl group covalently attached to the inner lipoyl domain of the E2 component. PDHA1 deficiency is the most common enzyme defect in patients with primary lactic acidosis. Suppression of PDH by PDHK inhibits the conversion of pyruvate to acetyl-CoA, attenuates mitochondrial respiration, and may contribute to the increased lactate production observed in many tumors. The PDH pathway is repressed in a majority of non-small cell lung carcinomas. Inhibited by AZD7545, dichloroacetate (DCA), and radicicol. Radicicol inhibits kinase activity by binding directly to the ATP-binding pocket of PDHK, similar to HSP90 from the same ATPase/kinase superfamily. Note: This description may include information from UniProtKB.
Protein type: ATYPICAL group; EC 2.7.11.2; Kinase, protein; Mitochondrial; PDHK family; PDHK subfamily; Protein kinase, atypical
Chromosomal Location of Human Ortholog: 11 D|11 59.01 cM
Cellular Component:  cytosol; mitochondrial pyruvate dehydrogenase complex; mitochondrion; nucleoplasm; pyruvate dehydrogenase complex
Molecular Function:  ATP binding; kinase activity; nucleotide binding; protein binding; protein heterodimerization activity; protein homodimerization activity; protein kinase activity; protein serine/threonine kinase activity; protein-containing complex binding; pyruvate dehydrogenase (acetyl-transferring) kinase activity; transferase activity
Biological Process:  carbohydrate metabolic process; cellular response to nutrient; cellular response to reactive oxygen species; glucose homeostasis; glucose metabolic process; insulin receptor signaling pathway; intrinsic apoptotic signaling pathway by p53 class mediator; peptidyl-serine phosphorylation; phosphorylation; protein phosphorylation; regulation of acetyl-CoA biosynthetic process from pyruvate; regulation of calcium-mediated signaling; regulation of cellular ketone metabolic process; regulation of gluconeogenesis; regulation of glucose metabolic process; regulation of pH
Reference #:  Q9JK42 (UniProtKB)
Alt. Names/Synonyms: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial; [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial; OTTMUSP00000001538; Pdk2; pyruvate dehydrogenase 2; Pyruvate dehydrogenase kinase isoform 2; pyruvate dehydrogenase kinase, isoenzyme 2; pyruvate dehydrogenase kinase, isozyme 2
Gene Symbols: Pdk2
Molecular weight: 46,041 Da
Basal Isoelectric point: 6.13  Predict pI for various phosphorylation states
CST Pathways:  Warburg Effect
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PDHK2

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene