Names & Taxonomy

Uniprot ID:
Q16654
Entry Name:
PDK4_HUMAN
Status:
reviewed
Protein Names:
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 4)
Gene Names:
PDK4 PDHK4
Gene Names Primary:
PDK4
Organism:
Homo sapiens (Human)

Structure

Length:
411
Sequence:
MKAARFVLRSAGSLNGAGLVPREVEHFSRYSPSPLSMKQLLDFGSENACERTSFAFLRQELPVRLANILKEIDILPTQLVNTSSVQLVKSWYIQSLMDLVEFHEKSPDDQKALSDFVDTLIKVRNRHHNVVPTMAQGIIEYKDACTVDPVTNQNLQYFLDRFYMNRISTRMLMNQHILIFSDSQTGNPSHIGSIDPNCDVVAVVQDAFECSRMLCDQYYLSSPELKLTQVNGKFPDQPIHIVYVPSHLHHMLFELFKNAMRATVEHQENQPSLTPIEVIVVLGKEDLTIKISDRGGGVPLRIIDRLFSYTYSTAPTPVMDNSRNAPLAGFGYGLPISRLYAKYFQGDLNLYSLSGYGTDAIIYLKALSSESIEKLPVFNKSAFKHYQMSSEADDWCIPSREPKNLAKEVAM
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Mitochondrion matrix.

Function

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.
Catalytic Activity:
ATP + = ADP + phosphate.
Gene Ontology Go:
mitochondrial inner membrane
mitochondrial matrix
mitochondrion
ATP binding
protein kinase activity
pyruvate dehydrogenase (acetyl-transferring) kinase activity
cellular metabolic process
cellular response to fatty acid
cellular response to starvation
glucose homeostasis
glucose metabolic process
insulin receptor signaling pathway
negative regulation of anoikis
positive regulation of defense response to virus by host
protein phosphorylation
pyruvate metabolic process
reactive oxygen species metabolic process
regulation of acetyl-CoA biosynthetic process from pyruvate
regulation of bone resorption
regulation of cellular ketone metabolic process
regulation of fatty acid biosynthetic process
regulation of fatty acid oxidation
regulation of glucose metabolic process
regulation of pH
response to starvation
small molecule metabolic process
xenophagy
Gene Ontology Biological Process:
cellular metabolic process
cellular response to fatty acid
cellular response to starvation
glucose homeostasis
glucose metabolic process
insulin receptor signaling pathway
negative regulation of anoikis
positive regulation of defense response to virus by host
protein phosphorylation
pyruvate metabolic process
reactive oxygen species metabolic process
regulation of acetyl-CoA biosynthetic process from pyruvate
regulation of bone resorption
regulation of cellular ketone metabolic process
regulation of fatty acid biosynthetic process
regulation of fatty acid oxidation
regulation of glucose metabolic process
regulation of pH
response to starvation
small molecule metabolic process
xenophagy
Gene Ontology Molecular Function:
ATP binding
protein kinase activity
pyruvate dehydrogenase (acetyl-transferring) kinase activity
Gene Ontology Cellular Component:
mitochondrial inner membrane
mitochondrial matrix
mitochondrion
Keywords:
3D-structure
ATP-binding
Carbohydrate metabolism
Complete proteome
Glucose metabolism
Kinase
Mitochondrion
Nucleotide-binding
Polymorphism
Reference proteome
Transferase
Transit peptide

Publication

PubMed ID:
8798399 12853948 15489334 14966024 15955060 17669420 21852536 20715114 21816445 18658136 21904029 17344846