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
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] |