UniProt functional annotation for Q15119



	UniProt functional annotation for Q15119

UniProt code: Q15119.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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:0000269|PubMed:17222789, ECO:0000269|PubMed:19833728, ECO:0000269|PubMed:21283817, ECO:0000269|PubMed:22123926, ECO:0000269|PubMed:7499431, ECO:0000269|PubMed:9787110}.

Catalytic activity: Reaction=ATP + L-seryl-[pyruvate dehydrogenase E1 alpha subunit] = ADP + H(+) + O-phospho-L-seryl-[pyruvate dehydrogenase E1 alpha subunit]; Xref=Rhea:RHEA:23052, Rhea:RHEA-COMP:13689, Rhea:RHEA-COMP:13690, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.2; Evidence={ECO:0000269|PubMed:15491150, ECO:0000269|PubMed:16517984, ECO:0000269|PubMed:19833728, ECO:0000269|PubMed:7499431};

Activity regulation: Activity is enhanced by binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by ADP and pyruvate; these compounds interfere with DLAT binding and thereby inhibit kinase activity. Inhibited by dichloroacetate. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. {ECO:0000269|PubMed:15491150, ECO:0000269|PubMed:16517984, ECO:0000269|PubMed:19833728}.

Subunit: Homodimer, and heterodimer with PDK1. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). {ECO:0000269|PubMed:12816949, ECO:0000269|PubMed:15491150, ECO:0000269|PubMed:16401071, ECO:0000269|PubMed:16517984, ECO:0000269|PubMed:19833728}.

Subcellular location: Mitochondrion matrix.

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:0000269|PubMed:7499431}.

Induction: Down-regulated by insulin. Up-regulated by reactive oxygen species and cigarette smoke extract. Up-regulated by PPARD. {ECO:0000269|PubMed:17669420, ECO:0000269|PubMed:21283817, ECO:0000269|PubMed:9787110}.

Similarity: Belongs to the PDK/BCKDK protein kinase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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:0000269\|PubMed:17222789, ECO:0000269\|PubMed:19833728, ECO:0000269\|PubMed:21283817, ECO:0000269\|PubMed:22123926, ECO:0000269\|PubMed:7499431, ECO:0000269\|PubMed:9787110}.


Catalytic activity:		Reaction=ATP + L-seryl-[pyruvate dehydrogenase E1 alpha subunit] = ADP + H(+) + O-phospho-L-seryl-[pyruvate dehydrogenase E1 alpha subunit]; Xref=Rhea:RHEA:23052, Rhea:RHEA-COMP:13689, Rhea:RHEA-COMP:13690, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.2; Evidence={ECO:0000269\|PubMed:15491150, ECO:0000269\|PubMed:16517984, ECO:0000269\|PubMed:19833728, ECO:0000269\|PubMed:7499431};
Activity regulation:		Activity is enhanced by binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by ADP and pyruvate; these compounds interfere with DLAT binding and thereby inhibit kinase activity. Inhibited by dichloroacetate. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. {ECO:0000269\|PubMed:15491150, ECO:0000269\|PubMed:16517984, ECO:0000269\|PubMed:19833728}.
Subunit:		Homodimer, and heterodimer with PDK1. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). {ECO:0000269\|PubMed:12816949, ECO:0000269\|PubMed:15491150, ECO:0000269\|PubMed:16401071, ECO:0000269\|PubMed:16517984, ECO:0000269\|PubMed:19833728}.
Subcellular location:		Mitochondrion matrix.
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:0000269\|PubMed:7499431}.
Induction:		Down-regulated by insulin. Up-regulated by reactive oxygen species and cigarette smoke extract. Up-regulated by PPARD. {ECO:0000269\|PubMed:17669420, ECO:0000269\|PubMed:21283817, ECO:0000269\|PubMed:9787110}.
Similarity:		Belongs to the PDK/BCKDK protein kinase family. {ECO:0000305}.