PDHK3 an atypical protein kinase associated with the mitochondrial matrix. The PDHKs play crucial roles in switching metabolic flux from oxidative phosphorylation towards glycolysis. PDHK3 is present in testes, kidney, and brain. 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; Protein kinase, atypical
Chromosomal Location of Human Ortholog: Xp22.11
Cellular Component:  mitochondrial matrix; mitochondrion; nucleolus
Molecular Function:  ATP binding; protein binding; protein kinase activity; protein serine/threonine kinase activity; pyruvate dehydrogenase (acetyl-transferring) kinase activity
Biological Process:  cellular response to fatty acid; cellular response to glucose stimulus; glucose metabolic process; hypoxia-inducible factor-1alpha signaling pathway; peptidyl-serine phosphorylation; peroxisome proliferator activated receptor signaling pathway; regulation of acetyl-CoA biosynthetic process from pyruvate; regulation of glucose metabolic process; regulation of reactive oxygen species metabolic process
Disease: Charcot-marie-tooth Disease, X-linked Dominant, 6
Reference #:  Q15120 (UniProtKB)
Alt. Names/Synonyms: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial; [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 3, mitochondrial; PDK3; Pyruvate dehydrogenase kinase isoform 3; pyruvate dehydrogenase kinase, isoenzyme 3; pyruvate dehydrogenase kinase, isozyme 3; pyruvate dehydrogenase, lipoamide, kinase isozyme 3, mitochondrial
Gene Symbols: PDK3
Molecular weight: 46,939 Da
Basal Isoelectric point: 8.46  Predict pI for various phosphorylation states
CST Pathways:  Warburg Effect
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PDHK3

Protein Structure Not Found.


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