UniProt Protein Function: | 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.Protein type: Kinase, protein; Protein kinase, atypical; Mitochondrial; EC 2.7.11.2; ATYPICAL group; PDHK familyCellular Component: mitochondrionMolecular Function: ATP binding; protein kinase activity; protein serine/threonine kinase activity; pyruvate dehydrogenase (acetyl-transferring) kinase activityBiological Process: peptidyl-serine phosphorylation; regulation of acetyl-CoA biosynthetic process from pyruvate |
UniProt Protein Details: | |
NCBI Summary: | |
UniProt Code: | Q922H2 |
NCBI GenInfo Identifier: | 61214393 |
NCBI Gene ID: | 236900 |
NCBI Accession: | Q922H2.1 |
UniProt Secondary Accession: | Q922H2,Q8BTX1 |
UniProt Related Accession: | Q922H2 |
Molecular Weight: | 47,923 Da |
NCBI Full Name: | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial |
NCBI Synonym Full Names: | pyruvate dehydrogenase kinase, isoenzyme 3 |
NCBI Official Symbol: | Pdk3Â Â |
NCBI Official Synonym Symbols: | AI035637; 2610001M10Rik  |
NCBI Protein Information: | pyruvate dehydrogenase kinase, isozyme 3 |
UniProt Protein Name: | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial |
UniProt Synonym Protein Names: | Pyruvate dehydrogenase kinase isoform 3 |
Protein Family: | |
UniProt Gene Name: | Pdk3Â Â |
UniProt Entry Name: | PDK3_MOUSE |