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Aliases for PDK4 Gene

Aliases for PDK4 Gene

  • Pyruvate Dehydrogenase Kinase 4 2 3 5
  • EC 2.7.11.2 4 56
  • Pyruvate Dehydrogenase Kinase, Isoenzyme 4 2
  • Pyruvate Dehydrogenase Kinase, Isozyme 4 2
  • Pyruvate Dehydrogenase Kinase Isoform 4 4
  • EC 2.7.11 56
  • PDHK4 4

External Ids for PDK4 Gene

Previous GeneCards Identifiers for PDK4 Gene

  • GC07M093748
  • GC07M094811
  • GC07M094826
  • GC07M094824
  • GC07M094857
  • GC07M095050
  • GC07M095212
  • GC07M089819

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 4) is a Protein Coding gene. Diseases associated with PDK4 include Diabetes Mellitus, Noninsulin-Dependent. Among its related pathways are Estrogen Receptor Pathway and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Gene Ontology (GO) annotations related to this gene include protein kinase activity and pyruvate dehydrogenase (acetyl-transferring) kinase activity. An important paralog of this gene is PDK1.

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

Additional gene information for PDK4 Gene

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

Genomics for PDK4 Gene

GeneHancer (GH) Regulatory Elements for PDK4 Gene

Promoters and enhancers for PDK4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH07I095594 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE dbSUPER 550.8 +0.3 317 3 PKNOX1 FOXA2 ATF1 SIN3A ZNF2 YY1 GLIS2 ZNF213 SP3 RXRA ENSG00000231170 PDK4 ENSG00000279525
GH07I095627 Enhancer 1.2 VISTA ENCODE 11 -33.3 -33291 4.7 INSM2 FEZF1 GLIS2 RCOR1 RXRA CEBPB REST ZNF488 TSHZ1 ZNF843 PDK4 ENSG00000231170 GC07P095617 LOC105375409
GH07I096302 Enhancer 1.2 Ensembl ENCODE 5.1 -707.5 -707458 2.6 PKNOX1 FOXA2 MLX ARNT ARID4B FEZF1 DMAP1 YY1 ZNF213 ZNF143 SLC25A13 PDK4 ENSG00000275834 GC07P096284
GH07I095511 Enhancer 1 Ensembl ENCODE 4.2 +84.7 84696 1.6 PKNOX1 BATF ZNF2 IRF4 RAD21 ZNF143 ATF7 BCLAF1 RUNX3 MIXL1 PON3 PON1 PDK4 GC07M095530 ENSG00000233942 ASB4
GH07I095439 Enhancer 1.1 FANTOM5 ENCODE 1.3 +155.0 154998 4.2 FOXA2 MLX ZFP64 ARID4B DMAP1 ETS1 YY1 TCF12 ATF7 RXRA PON1 PON3 PON2 PDK4 ASB4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around PDK4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the PDK4 gene promoter:

Genomic Locations for PDK4 Gene

Genomic Locations for PDK4 Gene
chr7:95,583,497-95,596,613
(GRCh38/hg38)
Size:
13,117 bases
Orientation:
Minus strand
chr7:95,212,809-95,225,925
(GRCh37/hg19)

Genomic View for PDK4 Gene

Genes around PDK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PDK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PDK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence 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

    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

Selected DME Specific Peptides for PDK4 Gene

Q16654:
  • HIGSIDP
  • SPSPLSMKQ
  • VYVPSHL
  • GGGVPLR
  • ELPVRLAN
  • SDRGGGV
  • VRNRHHNVVPTMAQGI
  • IYLKALS
  • QYFLDRFY
  • CTVDPVTNQ
  • GYGLPISRLYA
  • KNAMRAT

Post-translational modifications for PDK4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PDK4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for PDK4 Gene

Gene Families for PDK4 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Graphical View of Domain Structure for InterPro Entry

Q16654

UniProtKB/Swiss-Prot:

PDK4_HUMAN :
  • Belongs to the PDK/BCKDK protein kinase family.
Family:
  • Belongs to the PDK/BCKDK protein kinase family.
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,TAS 18658136
GO:0004740 pyruvate dehydrogenase (acetyl-transferring) kinase activity TAS,ISS --
GO:0005524 ATP binding IDA,IEA 18658136
GO:0016301 kinase activity IEA --
GO:0016740 transferase activity IEA --
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:

Animal Model Products

  • Taconic Biosciences Mouse Models for PDK4

Clone Products

  • Addgene plasmids for PDK4

No data available for Phenotypes From GWAS Catalog , Human Phenotype Ontology , Transcription Factor Targets 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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PDK4 gene
Compartment Confidence
mitochondrion 5
peroxisome 2
nucleus 1
cytosol 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

No data available for Subcellular locations from the Human Protein Atlas (HPA) for PDK4 Gene

Pathways & Interactions for PDK4 Gene

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

Pathways by source for PDK4 Gene

SIGNOR curated interactions for PDK4 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for PDK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005975 carbohydrate metabolic process IEA --
GO:0006006 glucose metabolic process IEA --
GO:0006468 protein phosphorylation IEA --
GO:0006885 regulation of pH ISS,IEA --
GO:0008286 insulin receptor signaling pathway IMP,IEA 21852536
genes like me logo Genes that share ontologies with PDK4: view

Drugs & Compounds for PDK4 Gene

(10) Drugs for PDK4 Gene - From: DrugBank, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tretinoin Approved, Investigational Nutra Target 242
4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol Experimental Pharma Target 0
CPI-613 Investigational Pharma PDH/α-KGDH inhibitor 0
ATP Investigational Nutra Agonist 0
AZD7545 Pharma PDHK inhibitor,potent and selective 0

(8) Additional Compounds for PDK4 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
Hydrogen phosphate
  • Biphosphate
  • Hydrogen orthophosphate
  • Hydrogen phosphate
  • Hydrogen phosphate anion
  • Hydrogen phosphate dianion
14066-19-4

(1) ApexBio Compounds for PDK4 Gene

Compound Action Cas Number
AZD7545 PDHK inhibitor,potent and selective 252017-04-2
genes like me logo Genes that share compounds with PDK4: view

Drug Products

Transcripts for PDK4 Gene

Unigene Clusters for PDK4 Gene

Pyruvate dehydrogenase kinase, isozyme 4:
Representative Sequences:

Clone Products

  • Addgene plasmids for PDK4

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 from GTEx, Illumina, BioGPS, and CGAP SAGE for PDK4 Gene

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

This gene is overexpressed in Muscle - Skeletal (x15.8).

Protein differential expression in normal tissues from HIPED for PDK4 Gene

This gene is overexpressed in Heart (35.4), Pancreas (9.1), and Adrenal (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for PDK4 Gene



Protein tissue co-expression partners for PDK4 Gene

NURSA nuclear receptor signaling pathways regulating expression of PDK4 Gene:

PDK4

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.

Evidence on tissue expression from TISSUES for PDK4 Gene

  • Nervous system(4.5)
  • Muscle(3.9)
  • Heart(3.5)
  • Liver(3.1)
  • Pancreas(3)
  • Spleen(2.3)
  • Adrenal gland(2.2)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with PDK4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for PDK4 Gene

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 33 34
  • 99.59 (n)
dog
(Canis familiaris)
Mammalia PDK4 33 34
  • 91.48 (n)
cow
(Bos Taurus)
Mammalia PDK4 33 34
  • 90.82 (n)
mouse
(Mus musculus)
Mammalia Pdk4 33 16 34
  • 86.44 (n)
oppossum
(Monodelphis domestica)
Mammalia PDK4 34
  • 86 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Pdk4 33
  • 85.87 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia PDK4 34
  • 74 (a)
OneToOne
chicken
(Gallus gallus)
Aves PDK4 33 34
  • 76.44 (n)
lizard
(Anolis carolinensis)
Reptilia PDK4 34
  • 63 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii pdk4 33 34
  • 68.07 (n)
fruit fly
(Drosophila melanogaster)
Insecta Pdk 35 34
  • 53 (a)
worm
(Caenorhabditis elegans)
Secernentea ZK370.5 35
  • 50 (a)
pdhk-2 34
  • 48 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PKP1 34
  • 22 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3938 34
  • 43 (a)
OneToMany
Species where no ortholog for PDK4 was found in the sources mined by GeneCards:
  • 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

(3) 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 Variation AA Info Type
rs864622014 uncertain-significance, Malignant tumor of prostate 95,596,235(-) A/C coding_sequence_variant, missense_variant
rs1000065458 -- 95,588,427(-) C/T intron_variant
rs1000216785 -- 95,589,370(-) T/C intron_variant
rs1000219296 -- 95,595,959(-) G/A intron_variant
rs1000270274 -- 95,595,344(-) C/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for PDK4 Gene

Variant ID Type Subtype PubMed ID
nsv1023193 CNV gain 25217958

Variation tolerance for PDK4 Gene

Residual Variation Intolerance Score: 47.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.44; 43.02% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PDK4 Gene

Human Gene Mutation Database (HGMD)
PDK4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PDK4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PDK4 Gene

Disorders for PDK4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for PDK4 Gene - From: Novoseek

Disorder Aliases PubMed IDs
diabetes mellitus, noninsulin-dependent
  • niddm
- elite association - COSMIC cancer census association via MalaCards
Search PDK4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PDK4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with PDK4: view

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

Publications for PDK4 Gene

  1. Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity. (PMID: 18658136) Wynn RM … Chuang DT (The Journal of biological chemistry 2008) 3 4 22 58
  2. Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta. (PMID: 17669420) Degenhardt T … Carlberg C (Journal of molecular biology 2007) 3 4 22 58
  3. Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells. (PMID: 15955060) Abbot EL … Yeaman SJ (The FEBS journal 2005) 3 4 22 58
  4. Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting. (PMID: 14966024) Spriet LL … Cameron-Smith D (Journal of applied physiology (Bethesda, Md. : 1985) 2004) 3 4 22 58
  5. [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 medical 2002) 3 22 44 58

Products for PDK4 Gene

  • Addgene plasmids for PDK4

Sources for PDK4 Gene

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