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Aliases for PDK4 Gene

Aliases for PDK4 Gene

  • Pyruvate Dehydrogenase Kinase, Isozyme 4 2 3
  • EC 2.7.11.2 4 64
  • Pyruvate Dehydrogenase Kinase, Isoenzyme 4 2
  • Pyruvate Dehydrogenase Kinase Isoform 4 4
  • EC 2.7.11 64
  • PDHK4 4

External Ids for PDK4 Gene

Summaries for PDK4 Gene

Entrez Gene Summary for PDK4 Gene

  • This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitrochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, thereby contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin. [provided by RefSeq, Jul 2008]

GeneCards Summary for PDK4 Gene

PDK4 (Pyruvate Dehydrogenase Kinase, Isozyme 4) is a Protein Coding gene. Among its related pathways are Nanog in Mammalian ESC Pluripotency and Metabolism. GO annotations related to this gene include protein serine/threonine kinase activity and pyruvate dehydrogenase (acetyl-transferring) kinase activity. An important paralog of this gene is PDK2.

UniProtKB/Swiss-Prot for PDK4 Gene

  • 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.

Gene Wiki entry for PDK4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PDK4 Gene

Genomics for PDK4 Gene

Genomic Location for PDK4 Gene

Start:
95,583,497 bp from pter
End:
95,596,613 bp from pter
Size:
13,117 bases
Orientation:
Minus strand

Genomic View for PDK4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for PDK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PDK4 Gene

Regulatory Elements for PDK4 Gene

Proteins for PDK4 Gene

  • Protein details for PDK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q16654-PDK4_HUMAN
    Recommended name:
    [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial
    Protein Accession:
    Q16654
    Secondary Accessions:

    Protein attributes for PDK4 Gene

    Size:
    411 amino acids
    Molecular mass:
    46469 Da
    Quaternary structure:
    • 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).

    Three dimensional structures from OCA and Proteopedia for PDK4 Gene

neXtProt entry for PDK4 Gene

Proteomics data for PDK4 Gene at MOPED

Post-translational modifications for PDK4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PDK4 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for PDK4 Gene

Gene Families for PDK4 Gene

Protein Domains for PDK4 Gene

UniProtKB/Swiss-Prot:

PDK4_HUMAN
Domain:
  • Contains 1 histidine kinase domain.:
    • Q16654
Family:
  • Belongs to the PDK/BCKDK protein kinase family.:
    • Q16654
genes like me logo Genes that share domains with PDK4: view

Function for PDK4 Gene

Molecular function for PDK4 Gene

GENATLAS Biochemistry: pyruvate dehydrogenase kinase 4,highly expressed in heart and skeletal muscle,regulating mitochondrial PDH activity
UniProtKB/Swiss-Prot CatalyticActivity: ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate.
UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction: Up-regulated by prolonged fasting, in glucose-deprived cells and in response to a high-fat diet. Down-regulated by insulin. Up-regulated by PPARD.

Enzyme Numbers (IUBMB) for PDK4 Gene

Gene Ontology (GO) - Molecular Function for PDK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IDA 18658136
GO:0004674 protein serine/threonine kinase activity --
GO:0004740 pyruvate dehydrogenase (acetyl-transferring) kinase activity ISS --
GO:0005524 ATP binding IDA 18658136
genes like me logo Genes that share ontologies with PDK4: view
genes like me logo Genes that share phenotypes with PDK4: view

Animal Models for PDK4 Gene

MGI Knock Outs for PDK4:

miRNA for PDK4 Gene

No data available for Transcription Factor Targeting and HOMER Transcription for PDK4 Gene

Localization for PDK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PDK4 Gene

Mitochondrion matrix.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PDK4 Gene COMPARTMENTS Subcellular localization image for PDK4 gene
Compartment Confidence
mitochondrion 5
cytosol 1
nucleus 1

Gene Ontology (GO) - Cellular Components for PDK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion TAS 8798399
GO:0005743 mitochondrial inner membrane IEA --
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with PDK4: view

Pathways for PDK4 Gene

genes like me logo Genes that share pathways with PDK4: view

Gene Ontology (GO) - Biological Process for PDK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002230 positive regulation of defense response to virus by host IMP 22020285
GO:0006006 glucose metabolic process IEA --
GO:0006090 pyruvate metabolic process TAS --
GO:0006468 protein phosphorylation TAS 8798399
GO:0006885 regulation of pH ISS --
genes like me logo Genes that share ontologies with PDK4: view

Compounds for PDK4 Gene

(3) HMDB Compounds for PDK4 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Hydrogen phosphate
  • Biphosphate
14066-19-4

(1) Drugbank Compounds for PDK4 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol
target

(12) Novoseek inferred chemical compound relationships for PDK4 Gene

Compound -log(P) Hits PubMed IDs
pyruvate 89.7 81
fatty acid 67.9 16
carnitine 62.1 7
glucose 59.4 31
glycogen 55.6 11
genes like me logo Genes that share compounds with PDK4: view

Transcripts for PDK4 Gene

Unigene Clusters for PDK4 Gene

Pyruvate dehydrogenase kinase, isozyme 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for PDK4 Gene

No ASD Table

Relevant External Links for PDK4 Gene

GeneLoc Exon Structure for
PDK4
ECgene alternative splicing isoforms for
PDK4

Expression for PDK4 Gene

mRNA expression in normal human tissues for PDK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PDK4 Gene

This gene is overexpressed in Muscle - Skeletal (15.8).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for PDK4 Gene

SOURCE GeneReport for Unigene cluster for PDK4 Gene Hs.8364

mRNA Expression by UniProt/SwissProt for PDK4 Gene

Q16654-PDK4_HUMAN
Tissue specificity: Ubiquitous; highest levels of expression in heart and skeletal muscle.
genes like me logo Genes that share expressions with PDK4: view

Orthologs for PDK4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PDK4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PDK4 36
  • 99.59 (n)
  • 99.76 (a)
PDK4 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia PDK4 36
  • 90.82 (n)
  • 92.8 (a)
PDK4 37
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PDK4 36
  • 91.48 (n)
  • 93.61 (a)
PDK4 37
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Pdk4 36
  • 86.44 (n)
  • 93.38 (a)
Pdk4 16
Pdk4 37
  • 92 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia PDK4 37
  • 86 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PDK4 37
  • 74 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Pdk4 36
  • 85.87 (n)
  • 92.89 (a)
chicken
(Gallus gallus)
Aves PDK4 36
  • 76.44 (n)
  • 79.56 (a)
PDK4 37
  • 78 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PDK4 37
  • 63 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii pdk4 36
  • 68.07 (n)
  • 72.7 (a)
pdk4 37
  • 67 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Pdk 37
  • 49 (a)
OneToMany
Pdk 38
  • 53 (a)
worm
(Caenorhabditis elegans)
Secernentea pdhk-2 37
  • 48 (a)
OneToMany
ZK370.5 38
  • 50 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PKP1 37
  • 22 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3938 37
  • 43 (a)
OneToMany
Species with no ortholog for PDK4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for PDK4 Gene

ENSEMBL:
Gene Tree for PDK4 (if available)
TreeFam:
Gene Tree for PDK4 (if available)

Paralogs for PDK4 Gene

Paralogs for PDK4 Gene

Selected SIMAP similar genes for PDK4 Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with PDK4: view

Variants for PDK4 Gene

Sequence variations from dbSNP and Humsavar for PDK4 Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type MAF
rs6930 -- 95,583,747(+) TTTTA(A/G)AGATA utr-variant-3-prime
rs6931 -- 95,583,590(+) AATAA(A/T)TTAAG utr-variant-3-prime
rs721828 -- 95,588,574(+) AGCTG(G/T)AGTGA intron-variant
rs1057830 -- 95,594,556(-) GGCAA(A/G)TGTCT intron-variant
rs2073977 -- 95,585,925(+) AGAGC(A/G)CACTG intron-variant

Relevant External Links for PDK4 Gene

HapMap Linkage Disequilibrium report
PDK4
Human Gene Mutation Database (HGMD)
PDK4

No data available for Structural Variations from Database of Genomic Variants (DGV) for PDK4 Gene

Disorders for PDK4 Gene

(1) University of Copenhagen DISEASES for PDK4 Gene

(6) Novoseek inferred disease relationships for PDK4 Gene

Disease -log(P) Hits PubMed IDs
insulin resistance 43.5 2
rhabdomyosarcoma 32.1 1
insulin sensitivity 23.7 4
niddm 16.2 3
atrophy 0 1

Relevant External Links for PDK4

Genetic Association Database (GAD)
PDK4
Human Genome Epidemiology (HuGE) Navigator
PDK4
genes like me logo Genes that share disorders with PDK4: view

No data available for UniProtKB/Swiss-Prot for PDK4 Gene

Publications for PDK4 Gene

  1. Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human. (PMID: 8798399) Rowles J. … Prochazka M. (J. Biol. Chem. 1996) 3 4 23
  2. Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting. (PMID: 14966024) Spriet L.L. … Cameron-Smith D. (J. Appl. Physiol. 2004) 3 4 23
  3. [Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal]. (PMID: 15776585) Che D. … Trivin F. (Dakar Med 2002) 3 23 49
  4. Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells. (PMID: 15955060) Abbot E.L. … Yeaman S.J. (FEBS J. 2005) 3 4 23
  5. Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity. (PMID: 18658136) Wynn R.M. … Chuang D.T. (J. Biol. Chem. 2008) 3 4 23

Products for PDK4 Gene

  • Addgene plasmids for PDK4

Sources for PDK4 Gene

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