Gene/Proteome Database (LMPD)

LMPD ID
LMP001563
Gene ID
27273
Species
Mus musculus (Mouse)
Gene Name
pyruvate dehydrogenase kinase, isoenzyme 4
Gene Symbol
Pdk4
Synonyms
AV005916
Alternate Names
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial; pyruvate dehydrogenase kinase 4; [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial
Chromosome
6
Map Location
6 A1|6 2.06 cM
EC Number
2.7.11.2

Proteins

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial
Refseq ID NP_038771
Protein GI 7305375
UniProt ID O70571
mRNA ID NM_013743
Length 412
RefSeq Status PROVISIONAL
MKAARFVMRSASSLSSASLVPREVELFSRYSPSPLSMKQLLDFGSENACERTSFAFLRQELPVRLANILKEIDILPDRLVNTPSVQLVKSWYIQSLMDLVEFHEKSPEDQKALSEFVDTLVKVRNRHHNVVPTMAQGILEYKDTCTVDPVTNQNLQYFLDRFYMNRISTRMLMNQHILIFSDSKTGNPSHIGSIDPNCDVVAVVQDAFECAKMLCDQYYLTSPELNLTQVNGKFPGQPIHIVYVPSHLHHMLFELFKNAMRATVEHQENRPSLTPVEATVVLGKEDLTIKISDRGGGVPLRITDRLFSYTYSTAPTPVMDNSRNAPLAGFGYGLPISRLYAKYFQGDLNLYSMSGYGTDAIIYLKALSSESVEKLPVFNKSAFKHYQMSSEADDWCIPSREPKNLAKEKLAV

Gene Information

Entrez Gene ID
27273
Gene Name
pyruvate dehydrogenase kinase, isoenzyme 4
Gene Symbol
Pdk4
Species
Mus musculus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005743 IDA:MGI C mitochondrial inner membrane
GO:0005739 IDA:MGI C mitochondrion
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0004674 IEA:UniProtKB-KW F protein serine/threonine kinase activity
GO:0004712 TAS:MGI F protein serine/threonine/tyrosine kinase activity
GO:0004740 ISS:UniProtKB F pyruvate dehydrogenase (acetyl-transferring) kinase activity
GO:0006086 TAS:MGI P acetyl-CoA biosynthetic process from pyruvate
GO:0071398 ISS:UniProtKB P cellular response to fatty acid
GO:0009267 ISS:UniProtKB P cellular response to starvation
GO:0042593 IMP:UniProtKB P glucose homeostasis
GO:0006006 IEA:UniProtKB-KW P glucose metabolic process
GO:0008286 IMP:UniProtKB P insulin receptor signaling pathway
GO:2000811 IEA:Ensembl P negative regulation of anoikis
GO:0006468 ISS:GOC P protein phosphorylation
GO:0072593 ISS:UniProtKB P reactive oxygen species metabolic process
GO:0010510 IMP:UniProtKB P regulation of acetyl-CoA biosynthetic process from pyruvate
GO:0045124 IMP:UniProtKB P regulation of bone resorption
GO:0010565 IMP:UniProtKB P regulation of cellular ketone metabolic process
GO:0042304 IMP:UniProtKB P regulation of fatty acid biosynthetic process
GO:0046320 IMP:UniProtKB P regulation of fatty acid oxidation
GO:0010906 IMP:UniProtKB P regulation of glucose metabolic process
GO:0006885 IMP:UniProtKB P regulation of pH
GO:0042594 IMP:UniProtKB P response to starvation

REACTOME Pathway Links

REACTOME Pathway ID Description
5892778 Pyruvate metabolism
5893557 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, isoenzyme 4
Protein Entry
PDK4_MOUSE
UniProt ID
O70571
Species
Mouse

Comments

Comment Type Description
Catalytic Activity ATP + [pyruvate dehydrogenase (acetyl- transferring)] = ADP + [pyruvate dehydrogenase (acetyl- transferring)] phosphate.
Disruption Phenotype No visible phenotype at birth. Mice have lower blood glucose and pyruvate levels after overnight fasting than normal, while the levels of ketone bodies are increased. After 48 h starving, their rate of glucose oxidation is increased, and glycolysis decreased, compared to wild type mice. Likewise, their rate of fatty acid oxidation is lower than normal in response to starvation. In contrast, there are no differences in blood glucose levels betwen fed mutant and wild type mice. In response to a high-fat diet, mutant mice have lower de novo fatty acid biosynthesis, and lower liver steatosis than wild-type. Mutant mice show normal bone formation and normal bone metabolism, excepting reduced bone loss when suspended to induce disuse osteoporosis. {ECO:0000269|PubMed:16606348, ECO:0000269|PubMed:18430968, ECO:0000269|PubMed:19627255, ECO:0000269|PubMed:21803180, ECO:0000269|PubMed:22360721, ECO:0000269|PubMed:22436846}.
Function Kinase that plays a key role in 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 in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. 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. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism. {ECO:0000269|PubMed:16606348, ECO:0000269|PubMed:18083902, ECO:0000269|PubMed:18430968, ECO:0000269|PubMed:19627255, ECO:0000269|PubMed:21321124, ECO:0000269|PubMed:22360721}.
Induction Up-regulated by PPARD. {ECO:0000269|PubMed:17669420}.
Similarity Belongs to the PDK/BCKDK protein kinase family. {ECO:0000305}.
Similarity Contains 1 histidine kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00107}.
Subcellular Location Mitochondrion matrix {ECO:0000250}.
Subunit Homodimer. 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) (By similarity). {ECO:0000250}.

Identical and Related Proteins

Unique RefSeq proteins for LMP001563 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
7305375 RefSeq NP_038771 412 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial

Identical Sequences to LMP001563 proteins

Reference Database Accession Length Protein Name
GI:7305375 DBBJ BAB23359.1 412 unnamed protein product [Mus musculus]
GI:7305375 DBBJ BAC29590.1 412 unnamed protein product [Mus musculus]
GI:7305375 GenBank AAG44393.1 412 pyruvate dehydrogenase kinase 4 [Mus musculus]
GI:7305375 GenBank AAH26134.1 412 Pyruvate dehydrogenase kinase, isoenzyme 4 [Mus musculus]
GI:7305375 GenBank EDL13963.1 412 pyruvate dehydrogenase kinase, isoenzyme 4 [Mus musculus]
GI:7305375 SwissProt O70571.1 412 RecName: Full=[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial; AltName: Full=Pyruvate dehydrogenase kinase isoform 4; Flags: Precursor [Mus musculus]

Related Sequences to LMP001563 proteins

Reference Database Accession Length Protein Name
GI:7305375 GenBank AAC00177.1 412 pyruvate dehydrogenase kinase isoenzyme 4 [Rattus norvegicus]
GI:7305375 GenBank EDM15025.1 412 pyruvate dehydrogenase kinase, isoenzyme 4 [Rattus norvegicus]
GI:7305375 RefSeq NP_446003.1 412 pyruvate dehydrogenase kinase, isozyme 4 [Rattus norvegicus]
GI:7305375 RefSeq XP_005363751.1 412 PREDICTED: Pyruvate dehydrogenase [lipoamide] kinase isoform X1 [Microtus ochrogaster]
GI:7305375 RefSeq XP_006986935.1 412 PREDICTED: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial [Peromyscus maniculatus bairdii]
GI:7305375 SwissProt O54937.1 412 RecName: Full=[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial; AltName: Full=Pyruvate dehydrogenase kinase isoform 4; Flags: Precursor [Rattus norvegicus]