InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PDK2

Summary

InnateDB Protein

IDBP-478524.4

Last Modified

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

Gene Symbol

PDK2

Protein Name

pyruvate dehydrogenase kinase, isozyme 2

Synonyms

PDHK2; PDKII;

Species

Homo sapiens

Ensembl Protein

ENSP00000420927

InnateDB Gene

IDBG-58067 (PDK2)

Protein Structure

UniProt Annotation

Function

Serine/threonine kinase that plays a key role in the 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. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. 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. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis. {ECO:0000269PubMed:17222789, ECO:0000269PubMed:19833728, ECO:0000269PubMed:21283817, ECO:0000269PubMed:22123926, ECO:0000269PubMed:7499431, ECO:0000269PubMed:9787110}.

Subcellular Localization

Mitochondrion matrix.

Disease Associations

Tissue Specificity

Expressed in many tissues, with the highest level in heart and skeletal muscle, intermediate levels in brain, kidney, pancreas and liver, and low levels in placenta and lung. {ECO:0000269PubMed:7499431}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	9 [view]
Protein-Protein	5 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

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:0005515	protein binding
GO:0005524	ATP binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0006006	glucose metabolic process
GO:0006090	pyruvate metabolic process
GO:0006111	regulation of gluconeogenesis
GO:0006468	protein phosphorylation
GO:0006885	regulation of pH
GO:0008286	insulin receptor signaling pathway
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:0031670	cellular response to nutrient
GO:0034614	cellular response to reactive oxygen species
GO:0042593	glucose homeostasis
GO:0044237	cellular metabolic process
GO:0044281	small molecule metabolic process
GO:0072332	intrinsic apoptotic signaling pathway by p53 class mediator

Cellular Component

GO:0005739	mitochondrion
GO:0005759	mitochondrial matrix
GO:0005967	mitochondrial pyruvate dehydrogenase complex

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

Q15119