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Protein Page:
PDHK1 (human)

Overview
PDHK1 an ubiquitously expressed, atypical protein kinase associated with the mitochondrial matrix. The PDHKs play crucial roles in switching metabolic flux from oxidative phosphorylation towards glycolysis. PDHK1 is detected in heart, pancreatic islets, and skeletal muscles. 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. PDHK1 is a direct HIF-1 target gene. 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: Kinase, protein; Mitochondrial; EC 2.7.11.2; Protein kinase, atypical; ATYPICAL group; PDHK family
Cellular Component: mitochondrion; mitochondrial matrix; mitochondrial pyruvate dehydrogenase complex
Molecular Function: protein serine/threonine kinase activity; protein binding; pyruvate dehydrogenase (acetyl-transferring) kinase activity; ATP binding; protein kinase activity
Biological Process: cellular metabolic process; cell proliferation; glucose metabolic process; regulation of acetyl-CoA biosynthetic process from pyruvate; pyruvate metabolic process; induction of apoptosis by oxidative stress; protein amino acid phosphorylation
Reference #:  Q15118 (UniProtKB)
Alt. Names/Synonyms: [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial; mitochondrial pyruvate dehydrogenase, lipoamide, kinase isoenzyme 1; PDK1; Pyruvate dehydrogenase kinase isoform 1; pyruvate dehydrogenase kinase, isoenzyme 1; pyruvate dehydrogenase kinase, isozyme 1
Gene Symbols: PDK1
Molecular weight: 49,244 Da
Basal Isoelectric point: 8.92  Predict pI for various phosphorylation states
CST Pathways:  Warburg Effect
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

PDHK1

Protein Structure Not Found.


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Sites Implicated In
intracellular localization: Y243‑p

Modification Sites and Domains  

Modification Sites in Parent Protein, Orthologs, and Isoforms  
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 S67-p KQFLDFGsVNACEKT
1 3 Y136-p AEDAKAIyDFTDTVI
1 2 Y243-p ARRLCDLyyINSPEL
1 2 Y244-p RRLCDLyyINSPELE
0 1 Y336-p DRLFNYMySTAPRPR
0 3 T346-p APRPRVEtsRAVPLA
0 3 S347-p PRPRVEtsRAVPLAG
0 1 Y357-p VPLAGFGyGLPISRL
0 1 Y403-p SIERLPVyNKAAWKH
  mouse

 
S67 KQFLDFGSVNACEKT
Y136-p AEDAKTIyEFTDTVI
Y241-p ARRLCDLyyVNSPEL
Y242-p RRLCDLyyVNSPELE
Y334 DRLFNYMYSTAPRPR
T344-p APRPRVEtsRAVPLA
S345-p PRPRVEtsRAVPLAG
Y355 VPLAGFGYGLPISRL
Y401 SVERLPVYNKAAWKH
  rat

 
S67 KQFLDFGSVNACEKT
Y136 AEDAKTIYEFTDTVI
Y241 ARRLCDLYYVNSPEL
Y242 RRLCDLYYVNSPELE
Y334 DRLFNYMYSTAPRPR
T344 APRPRVETSRAVPLA
S345 PRPRVETSRAVPLAG
Y355 VPLAGFGYGLPISRL
Y401 SIERLPVYNKAAWKH
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