Gene/Proteome Database (LMPD)

LMPD ID
LMP012757
Gene ID
Species
Rattus norvegicus (Rat)
Gene Name
pyruvate dehydrogenase kinase, isozyme 2
Gene Symbol
Alternate Names
pyruvate dehydrogenase kinase, isozyme 2; PDK P45; PDH kinase 2; pyruvate dehydrogenase 2; pyruvate dehydrogenase kinase, isoenzyme 2; pyruvate dehydrogenase kinase 2 subunit p45 (PDK2); [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial; [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial;
Chromosome
10
Map Location
10q31
EC Number
2.7.11.2
Summary
catalyzes the phosphorylation and inactivation of the pyruvate dehydrogenase complex; plays a role in the regulation of glucose oxidation [RGD, Feb 2006]
Orthologs

Proteins

pyruvate dehydrogenase kinase, isozyme 2
Refseq ID NP_110499
Protein GI 13540705
UniProt ID Q64536
mRNA ID NM_030872
Length 407
MRWFRALLKNASLAGAPKYIEHFSKFSPSPLSMKQFLDFGSSNACEKTSFTFLRQELPVRLANIMKEINLLPDRVLSTPSVQLVQSWYVQSLLDIMEFLDKDPEDHRTLSQFTDALVTIRNRHNDVVPTMAQGVLEYKDTYGDDPVSNQNIQYFLDRFYLSRISIRMLINQHTLIFDGSTNPAHPKHIGSIDPNCSVSDVVKDAYDMAKLLCDKYYMASPDLEIQEVNATNATQPIHMVYVPSHLYHMLFELFKNAMRATVESHESSLTLPPIKIMVALGEEDLSIKMSDRGGGVPLRKIERLFSYMYSTAPTPQPGTGGTPLAGFGYGLPISRLYAKYFQGDLQLFSMEGFGTDAVIYLKALSTDSVERLPVYNKSAWRHYQTIQEAGDWCVPSTEPKNTSTYRVS

Gene Information

Entrez Gene ID
Gene Name
pyruvate dehydrogenase kinase, isozyme 2
Gene Symbol
Species
Rattus norvegicus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005967 ISS:UniProtKB C mitochondrial pyruvate dehydrogenase complex
GO:0005739 IDA:RGD C mitochondrion
GO:0045254 IDA:RGD C pyruvate dehydrogenase complex
GO:0005524 IDA:RGD F ATP binding
GO:0032403 IDA:RGD F protein complex binding
GO:0046982 IDA:RGD F protein heterodimerization activity
GO:0042803 IDA:RGD F protein homodimerization activity
GO:0004674 IDA:UniProtKB F protein serine/threonine kinase activity
GO:0004740 IDA:UniProtKB F pyruvate dehydrogenase (acetyl-transferring) kinase activity
GO:0031670 ISS:UniProtKB P cellular response to nutrient
GO:0042593 ISS:UniProtKB P glucose homeostasis
GO:0006006 IEA:UniProtKB-KW P glucose metabolic process
GO:0008286 ISS:UniProtKB P insulin receptor signaling pathway
GO:0018105 IDA:UniProtKB P peptidyl-serine phosphorylation
GO:0006468 IDA:RGD P protein phosphorylation
GO:0010510 ISS:UniProtKB P regulation of acetyl-CoA biosynthetic process from pyruvate
GO:0010565 ISS:UniProtKB P regulation of cellular ketone metabolic process
GO:0006111 ISS:UniProtKB P regulation of gluconeogenesis
GO:0010906 ISS:UniProtKB P regulation of glucose metabolic process
GO:0006885 ISS:UniProtKB P regulation of pH

Domain Information

InterPro Annotations

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

UniProt Annotations

Entry Information

Gene Name
pyruvate dehydrogenase kinase, isozyme 2
Protein Entry
PDK2_RAT
UniProt ID
Species
Rat

Comments

Comment Type Description
Catalytic Activity ATP + [pyruvate dehydrogenase (acetyl- transferring)] = ADP + [pyruvate dehydrogenase (acetyl- transferring)] phosphate. {ECO:0000269|PubMed:11486000, ECO:0000269|PubMed:12573248, ECO:0000269|PubMed:18387944, ECO:0000269|PubMed:22910903, ECO:0000269|PubMed:7961963, ECO:0000269|PubMed:9405293}.
Enzyme Regulation Activity increases in response to increased acetyl-CoA and NADH levels and upon 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. Reactive oxygen species cause the formation of disulfide bonds, and thereby inhibit the enzyme
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:11486000, ECO:0000269|PubMed:12573248, ECO:0000269|PubMed:14641018, ECO:0000269|PubMed:22910903, ECO:0000269|PubMed:7961963}.
Similarity Belongs to the PDK/BCKDK protein kinase family
Similarity Contains 1 histidine kinase domain
Subcellular Location Mitochondrion matrix .
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:11483605, ECO:0000269|PubMed:11978179, ECO:0000269|PubMed:12573248, ECO:0000269|PubMed:18387944}.
Tissue Specificity Detected in heart (at protein level). Highest level of expression in heart and skeletal muscle and the lowest in spleen and lung. Liver, kidney, brain and testis levels are intermediate. {ECO:0000269|PubMed:22910903, ECO:0000269|PubMed:7961963, ECO:0000269|PubMed:9405293}.

Identical and Related Proteins

Unique RefSeq proteins for LMP012757 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
13540705 RefSeq NP_110499 407 pyruvate dehydrogenase kinase, isozyme 2

Identical Sequences to LMP012757 proteins

Reference Database Accession Length Protein Name
GI:13540705 GenBank AEK13626.1 407 Sequence 38 from patent US 7972785
GI:13540705 PDB 3CRK 407 Chain B, Crystal Structure Of The Pdhk2-L2 Complex.
GI:13540705 PDB 3CRL 407 Chain A, Crystal Structure Of The Pdhk2-L2 Complex.
GI:13540705 PDB 3CRL 407 Chain B, Crystal Structure Of The Pdhk2-L2 Complex.

Related Sequences to LMP012757 proteins

Reference Database Accession Length Protein Name
GI:13540705 GenBank AAH61823.1 407 Pyruvate dehydrogenase kinase, isozyme 2 [Rattus norvegicus]
GI:13540705 PDB 1JM6 407 Chain A, Pyruvate Dehydrogenase Kinase, Isozyme 2, Containing Adp
GI:13540705 PDB 1JM6 407 Chain B, Pyruvate Dehydrogenase Kinase, Isozyme 2, Containing Adp