InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PDK4

Summary

InnateDB Protein

IDBP-27871.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PDK4

Protein Name

pyruvate dehydrogenase kinase, isozyme 4

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000005178

InnateDB Gene

IDBG-27869 (PDK4)

Protein Structure

UniProt Annotation

Function

Serine/threonine 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. {ECO:0000269PubMed:15955060, ECO:0000269PubMed:18658136, ECO:0000269PubMed:21816445, ECO:0000269PubMed:21852536}.

Subcellular Localization

Mitochondrion matrix.

Disease Associations

Tissue Specificity

Ubiquitous; highest levels of expression in heart and skeletal muscle. {ECO:0000269PubMed:14966024, ECO:0000269PubMed:21816445}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.

Experimentally validated
Total	6 [view]
Protein-Protein	3 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004740	pyruvate dehydrogenase (acetyl-transferring) kinase activity
GO:0005524	ATP binding

Biological Process

GO:0006006	glucose metabolic process
GO:0006090	pyruvate metabolic process
GO:0006468	protein phosphorylation
GO:0006885	regulation of pH
GO:0008286	insulin receptor signaling pathway
GO:0009267	cellular response to starvation
GO:0010510	regulation of acetyl-CoA biosynthetic process from pyruvate
GO:0010565	regulation of cellular ketone metabolic process
GO:0010906	regulation of glucose metabolic process
GO:0042304	regulation of fatty acid biosynthetic process
GO:0042593	glucose homeostasis
GO:0042594	response to starvation
GO:0044237	cellular metabolic process
GO:0044281	small molecule metabolic process
GO:0045124	regulation of bone resorption
GO:0046320	regulation of fatty acid oxidation
GO:0071398	cellular response to fatty acid
GO:0072593	reactive oxygen species metabolic process
GO:2000811	negative regulation of anoikis

Cellular Component

GO:0005739	mitochondrion
GO:0005743	mitochondrial inner membrane
GO:0005759	mitochondrial matrix

Protein Structure and Domains

PDB ID

InterPro

IPR003594 Histidine kinase-like ATPase, C-terminal domain
IPR005467 Signal transduction histidine kinase, core
IPR018955 Branched-chain alpha-ketoacid dehydrogenase kinase/Pyruvate dehydrogenase kinase, N-terminal

PFAM

PF02518
PF13581
PF10436

PRINTS

PIRSF

SMART

SM00387

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q16654