General Information of Target

Target ID LDTP06595
Target Name [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial (PDK4)
Gene Name PDK4
Gene ID 5166
Synonyms
PDHK4; [Pyruvate dehydrogenase; acetyl-transferring)] kinase isozyme 4, mitochondrial; EC 2.7.11.2; Pyruvate dehydrogenase kinase isoform 4
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MKAARFVLRSAGSLNGAGLVPREVEHFSRYSPSPLSMKQLLDFGSENACERTSFAFLRQE
LPVRLANILKEIDILPTQLVNTSSVQLVKSWYIQSLMDLVEFHEKSPDDQKALSDFVDTL
IKVRNRHHNVVPTMAQGIIEYKDACTVDPVTNQNLQYFLDRFYMNRISTRMLMNQHILIF
SDSQTGNPSHIGSIDPNCDVVAVVQDAFECSRMLCDQYYLSSPELKLTQVNGKFPDQPIH
IVYVPSHLHHMLFELFKNAMRATVEHQENQPSLTPIEVIVVLGKEDLTIKISDRGGGVPL
RIIDRLFSYTYSTAPTPVMDNSRNAPLAGFGYGLPISRLYAKYFQGDLNLYSLSGYGTDA
IIYLKALSSESIEKLPVFNKSAFKHYQMSSEADDWCIPSREPKNLAKEVAM
Target Bioclass
Enzyme
Family
PDK/BCKDK protein kinase family
Subcellular location
Mitochondrion matrix
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. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism.
Uniprot ID
Q16654
Ensemble ID
ENST00000005178.6
HGNC ID
HGNC:8812
ChEMBL ID
CHEMBL4141

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IA-alkyne
 Probe Info 
C396(2.31)  LDD2157  [1]
Acrolein
 Probe Info 
N.A.  LDD0225  [2]
IPM
 Probe Info 
N.A.  LDD0025  [3]
TFBX
 Probe Info 
C215(0.00); C49(0.00)  LDD0027  [3]
DBIA
 Probe Info 
C49(0.31)  LDD2236  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0109  NEM HeLa N.A.  LDD0225  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Pleckstrin homology domain-containing family F member 2 (PLEKHF2) . Q9H8W4

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Tretinoin Small molecular drug DB00755
Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
4-[4-(4-methoxyphenyl)-5-methyl-1h-pyrazol-3-yl]Benzene-13-diol . DB08356

References

1 From chemoproteomic-detected amino acids to genomic coordinates: insights into precise multi-omic data integration. Mol Syst Biol. 2021 Feb;17(2):e9840. doi: 10.15252/msb.20209840.
Mass spectrometry data entry: PXD022151
2 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
3 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
4 Global profiling of phosphorylation-dependent changes in cysteine reactivity. Nat Methods. 2022 Mar;19(3):341-352. doi: 10.1038/s41592-022-01398-2. Epub 2022 Feb 28.
Mass spectrometry data entry: PXD026730