Gene/Proteome Database (LMPD)

LMPD ID
LMP000514
Gene ID
Species
Homo sapiens (Human)
Gene Name
pyruvate dehydrogenase kinase, isozyme 2
Gene Symbol
Synonyms
PDHK2; PDKII
Alternate Names
pyruvate dehydrogenase kinase, isozyme 2; PDH kinase 2; pyruvate dehydrogenase kinase, isoenzyme 2; pyruvate dehydrogenase, lipoamide, kinase isozyme 2, mitochondrial; [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial
Chromosome
17
Map Location
17q21.33
EC Number
2.7.11.2
Summary
This gene encodes a member of the pyruvate dehydrogenase kinase family. The encoded protein phosphorylates pyruvate dehydrogenase, down-regulating the activity of the mitochondrial pyruvate dehydrogenase complex. Overexpression of this gene may play a role in both cancer and diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]
Orthologs

Proteins

pyruvate dehydrogenase kinase, isozyme 2 isoform 1 precursor
Refseq ID NP_002602
Protein GI 19923736
UniProt ID Q15119
mRNA ID NM_002611
Length 407
RefSeq Status REVIEWED
MRWVWALLKNASLAGAPKYIEHFSKFSPSPLSMKQFLDFGSSNACEKTSFTFLRQELPVRLANIMKEINLLPDRVLSTPSVQLVQSWYVQSLLDIMEFLDKDPEDHRTLSQFTDALVTIRNRHNDVVPTMAQGVLEYKDTYGDDPVSNQNIQYFLDRFYLSRISIRMLINQHTLIFDGSTNPAHPKHIGSIDPNCNVSEVVKDAYDMAKLLCDKYYMASPDLEIQEINAANSKQPIHMVYVPSHLYHMLFELFKNAMRATVESHESSLILPPIKVMVALGEEDLSIKMSDRGGGVPLRKIERLFSYMYSTAPTPQPGTGGTPLAGFGYGLPISRLYAKYFQGDLQLFSMEGFGTDAVIYLKALSTDSVERLPVYNKSAWRHYQTIQEAGDWCVPSTEPKNTSTYRVS
pyruvate dehydrogenase kinase, isozyme 2 isoform 2
Refseq ID NP_001186827
Protein GI 315630349
UniProt ID Q15119
mRNA ID NM_001199898
Length 343
RefSeq Status REVIEWED
MKEINLLPDRVLSTPSVQLVQSWYVQSLLDIMEFLDKDPEDHRTLSQFTDALVTIRNRHNDVVPTMAQGVLEYKDTYGDDPVSNQNIQYFLDRFYLSRISIRMLINQHTLIFDGSTNPAHPKHIGSIDPNCNVSEVVKDAYDMAKLLCDKYYMASPDLEIQEINAANSKQPIHMVYVPSHLYHMLFELFKNAMRATVESHESSLILPPIKVMVALGEEDLSIKMSDRGGGVPLRKIERLFSYMYSTAPTPQPGTGGTPLAGFGYGLPISRLYAKYFQGDLQLFSMEGFGTDAVIYLKALSTDSVERLPVYNKSAWRHYQTIQEAGDWCVPSTEPKNTSTYRVS
pyruvate dehydrogenase kinase, isozyme 2 isoform 2
Refseq ID NP_001186828
Protein GI 315630351
UniProt ID Q15119
mRNA ID NM_001199899
Length 343
RefSeq Status REVIEWED
Protein sequence is identical to GI:315630349 (mRNA isoform)

Gene Information

Entrez Gene ID
Gene Name
pyruvate dehydrogenase kinase, isozyme 2
Gene Symbol
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005759 TAS:Reactome C mitochondrial matrix
GO:0005967 ISS:UniProtKB C mitochondrial pyruvate dehydrogenase complex
GO:0005524 IDA:UniProtKB F ATP binding
GO:0042803 IPI:UniProtKB F protein homodimerization activity
GO:0004672 TAS:ProtInc F protein kinase activity
GO:0004674 IEA:UniProtKB-KW F protein serine/threonine kinase activity
GO:0004740 IDA:UniProtKB F pyruvate dehydrogenase (acetyl-transferring) kinase activity
GO:0044237 TAS:Reactome P cellular metabolic process
GO:0031670 ISS:UniProtKB P cellular response to nutrient
GO:0034614 IMP:UniProtKB P cellular response to reactive oxygen species
GO:0042593 ISS:UniProtKB P glucose homeostasis
GO:0006006 TAS:ProtInc P glucose metabolic process
GO:0008286 ISS:UniProtKB P insulin receptor signaling pathway
GO:0072332 IMP:UniProtKB P intrinsic apoptotic signaling pathway by p53 class mediator
GO:0006468 IDA:GOC P protein phosphorylation
GO:0006090 TAS:Reactome P pyruvate metabolic process
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
GO:0044281 TAS:Reactome P small molecule metabolic process

REACTOME Pathway Links

REACTOME Pathway ID Description
REACT_2071 Pyruvate metabolism
REACT_1046 Pyruvate metabolism and Citric Acid (TCA) cycle
REACT_12528 Regulation of pyruvate dehydrogenase (PDH) complex

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_HUMAN
UniProt ID
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q15119-1; Sequence=Displayed; Name=2; IsoId=Q15119-2; Sequence=VSP_042549; Note=No experimental confirmation available.;
Catalytic Activity ATP + [pyruvate dehydrogenase (acetyl- transferring)] = ADP + [pyruvate dehydrogenase (acetyl- transferring)] phosphate. {ECO
Enzyme 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
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
Induction Down-regulated by insulin. Up-regulated by reactive oxygen species and cigarette smoke extract. Up-regulated by PPARD. {ECO
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
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.

Identical and Related Proteins

Unique RefSeq proteins for LMP000514 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
19923736 RefSeq NP_002602 407 pyruvate dehydrogenase kinase, isozyme 2 isoform 1 precursor
315630349 RefSeq NP_001186827 343 pyruvate dehydrogenase kinase, isozyme 2 isoform 2

Identical Sequences to LMP000514 proteins

Reference Database Accession Length Protein Name
GI:19923736 GenBank AHD78594.1 407 Sequence 26592 from patent US 8586006
GI:19923736 GenBank AIC49359.1 407 PDK2, partial [synthetic construct]
GI:19923736 GenBank AIC62543.1 407 PDK2, partial [synthetic construct]
GI:315630349 RefSeq XP_004041369.1 343 PREDICTED: [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial isoform 2 [Gorilla gorilla gorilla]
GI:315630349 RefSeq XP_004041370.1 343 PREDICTED: [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial isoform 3 [Gorilla gorilla gorilla]
GI:19923736 RefSeq XP_005583706.1 407 PREDICTED: Pyruvate dehydrogenase lipoamide kinase isozyme 2, mitochondrial isoform X1 [Macaca fascicularis]
GI:315630349 RefSeq XP_005583709.1 343 PREDICTED: Pyruvate dehydrogenase lipoamide kinase isozyme 2, mitochondrial isoform X4 [Macaca fascicularis]
GI:315630349 RefSeq XP_008009724.1 343 PREDICTED: pyruvate dehydrogenase kinase, isozyme 2 isoform X1 [Chlorocebus sabaeus]
GI:315630349 RefSeq XP_008009726.1 343 PREDICTED: pyruvate dehydrogenase kinase, isozyme 2 isoform X1 [Chlorocebus sabaeus]
GI:19923736 RefSeq XP_008009727.1 407 PREDICTED: pyruvate dehydrogenase kinase, isozyme 2 isoform X2 [Chlorocebus sabaeus]
GI:19923736 RefSeq XP_010384422.1 407 PREDICTED: pyruvate dehydrogenase kinase, isozyme 2 isoform X1 [Rhinopithecus roxellana]
GI:315630349 RefSeq XP_010384424.1 343 PREDICTED: pyruvate dehydrogenase kinase, isozyme 2 isoform X3 [Rhinopithecus roxellana]

Related Sequences to LMP000514 proteins

Reference Database Accession Length Protein Name
GI:315630349 DBBJ BAE01758.1 407 unnamed protein product [Macaca fascicularis]
GI:315630349 GenBank AAH05811.1 407 Pyruvate dehydrogenase kinase, isozyme 2 [Homo sapiens]
GI:19923736 GenBank AAQ02453.1 408 pyruvate dehydrogenase kinase, isoenzyme 2, partial [synthetic construct]
GI:19923736 GenBank ACM80750.1 407 Sequence 6248 from patent US 6812339
GI:19923736 GenBank ACM84229.1 423 Sequence 9727 from patent US 6812339
GI:315630349 GenBank AFE78701.1 407 pyruvate dehydrogenase kinase, isozyme 2 isoform 1 precursor [Macaca mulatta]
GI:315630349 GenBank AFH32756.1 407 pyruvate dehydrogenase kinase, isozyme 2 isoform 1 precursor [Macaca mulatta]
GI:315630349 GenBank AHD78594.1 407 Sequence 26592 from patent US 8586006
GI:19923736 PRF - 407 pyruvate dehydrogenase kinase:ISOTYPE=2 [Homo sapiens]
GI:19923736 RefSeq XP_523791.3 454 PREDICTED: pyruvate dehydrogenase kinase, isozyme 2 [Pan troglodytes]
GI:19923736 RefSeq XP_003817511.1 454 PREDICTED: pyruvate dehydrogenase kinase, isozyme 2 [Pan paniscus]
GI:315630349 RefSeq XP_005583706.1 407 PREDICTED: Pyruvate dehydrogenase lipoamide kinase isozyme 2, mitochondrial isoform X1 [Macaca fascicularis]