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Aliases for PDK1 Gene

Aliases for PDK1 Gene

  • Pyruvate Dehydrogenase Kinase 1 2 3 5
  • EC 2.7.11.2 4 61
  • Pyruvate Dehydrogenase Kinase, Isoenzyme 1 2
  • Pyruvate Dehydrogenase Kinase, Isozyme 1 2
  • Pyruvate Dehydrogenase Kinase Isoform 1 4
  • PDH Kinase 1 4
  • EC 2.7.11 61
  • PDHK1 4

External Ids for PDK1 Gene

Previous GeneCards Identifiers for PDK1 Gene

  • GC02P171473
  • GC02P172081
  • GC02P173384
  • GC02P173623
  • GC02P173246
  • GC02P173129
  • GC02P165298
  • GC02P173420

Summaries for PDK1 Gene

Entrez Gene Summary for PDK1 Gene

  • Pyruvate dehydrogenase (PDH) is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK) results in inactivation. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]

GeneCards Summary for PDK1 Gene

PDK1 (Pyruvate Dehydrogenase Kinase 1) is a Protein Coding gene. Diseases associated with PDK1 include Chronic Mountain Sickness. Among its related pathways are Metabolism and Pyruvate metabolism and Citric Acid (TCA) cycle. GO annotations related to this gene include protein kinase activity and pyruvate dehydrogenase (acetyl-transferring) kinase activity. An important paralog of this gene is PDK2.

UniProtKB/Swiss-Prot for PDK1 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. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress.

Gene Wiki entry for PDK1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PDK1 Gene

Genomics for PDK1 Gene

Regulatory Elements for PDK1 Gene

Enhancers for PDK1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02F172513 1.2 FANTOM5 Ensembl ENCODE 20 -41.1 -41072 1.4 SMARCE1 HDAC1 ATF1 RNF2 TAL1 ZBTB11 MAX NR2F2 ARID1B FOXK2 PDK1 ENSG00000225205 GC02P172522 GC02P172474
GH02F172495 1.1 FANTOM5 Ensembl ENCODE 19.4 -59.0 -59041 2.0 PDK1 ENSG00000225205 ENSG00000232788 ITGA6 GC02P172474 GC02P172522
GH02F172600 0.6 ENCODE 14.1 +45.5 45543 1.0 HDAC1 CBX3 ATF1 ARNT TBL1XR1 CHAMP1 GATA2 ETV6 BCLAF1 CREM PDK1 ENSG00000199866 GC02M172559 GC02M172611
GH02F172552 0.2 ENCODE 14 -0.2 -179 6.1 HDGF PKNOX1 ARNT CREB3L1 MLX WRNIP1 ARID4B SIN3A DMAP1 ZNF2 PDK1 HAT1 GC02P172546
GH02F172587 0.6 FANTOM5 11.5 +32.4 32351 0.2 NFYB PDK1 ENSG00000225205 METAP1D GC02M172559 ENSG00000199866 GC02M172611
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around PDK1 on UCSC Golden Path with GeneCards custom track

Promoters for PDK1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000602463 1027 2801 HDGF PKNOX1 CREB3L1 MLX WRNIP1 ARID4B SIN3A DMAP1 ZNF2 YY1

Genomic Location for PDK1 Gene

Chromosome:
2
Start:
172,555,373 bp from pter
End:
172,670,881 bp from pter
Size:
115,509 bases
Orientation:
Plus strand

Genomic View for PDK1 Gene

Genes around PDK1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PDK1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PDK1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PDK1 Gene

Proteins for PDK1 Gene

  • Protein details for PDK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q15118-PDK1_HUMAN
    Recommended name:
    [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial
    Protein Accession:
    Q15118
    Secondary Accessions:
    • B2R6T1
    • B7Z937
    • D3DPD8
    • E9PD65
    • Q308M4

    Protein attributes for PDK1 Gene

    Size:
    436 amino acids
    Molecular mass:
    49244 Da
    Quaternary structure:
    • Homodimer, and heterodimer with PDK2. 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 PDK1 Gene

    Alternative splice isoforms for PDK1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PDK1 Gene

Post-translational modifications for PDK1 Gene

  • Phosphorylated by constitutively activated ABL1, FGFR1, FLT3 and JAK2 (in vitro), and this may also occur in cancer cells that express constitutively activated ABL1, FGFR1, FLT3 and JAK2. Phosphorylation at Tyr-243 and Tyr-244 strongly increases kinase activity, while phosphorylation at Tyr-136 has a lesser effect.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for PDK1 (PDHK1)
  • Santa Cruz Biotechnology (SCBT) Antibodies for PDK1

Domains & Families for PDK1 Gene

Protein Domains for PDK1 Gene

Graphical View of Domain Structure for InterPro Entry

Q15118

UniProtKB/Swiss-Prot:

PDK1_HUMAN :
  • Contains 1 histidine kinase domain.
  • Belongs to the PDK/BCKDK protein kinase family.
Domain:
  • Contains 1 histidine kinase domain.
Family:
  • Belongs to the PDK/BCKDK protein kinase family.
genes like me logo Genes that share domains with PDK1: view

No data available for Gene Families for PDK1 Gene

Function for PDK1 Gene

Molecular function for PDK1 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activity is enhanced by binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. Inhibited by dichloroacetate and radicicol.
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. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress.
UniProtKB/Swiss-Prot Induction:
Up-regulated via the HIF1A signaling pathway in response to hypoxia.

Enzyme Numbers (IUBMB) for PDK1 Gene

Gene Ontology (GO) - Molecular Function for PDK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IDA,TAS 17683942
GO:0004740 pyruvate dehydrogenase (acetyl-transferring) kinase activity EXP,IMP 22195962
GO:0005515 protein binding IPI 17110931
GO:0005524 ATP binding IEA --
GO:0016301 kinase activity IEA --
genes like me logo Genes that share ontologies with PDK1: view
genes like me logo Genes that share phenotypes with PDK1: view

Animal Models for PDK1 Gene

MGI Knock Outs for PDK1:
  • Pdk1 tm1.1(KOMP)Vlcg

Animal Model Products

  • Taconic Biosciences Mouse Models for PDK1

Inhibitory RNA Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PDK1 Gene

Localization for PDK1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PDK1 Gene

Mitochondrion matrix.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PDK1 Gene COMPARTMENTS Subcellular localization image for PDK1 gene
Compartment Confidence
mitochondrion 5

Gene Ontology (GO) - Cellular Components for PDK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion TAS 7499431
GO:0005759 mitochondrial matrix TAS --
GO:0005967 mitochondrial pyruvate dehydrogenase complex IEA --
genes like me logo Genes that share ontologies with PDK1: view

Pathways & Interactions for PDK1 Gene

genes like me logo Genes that share pathways with PDK1: view

SIGNOR curated interactions for PDK1 Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for PDK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005975 carbohydrate metabolic process IEA --
GO:0006006 glucose metabolic process IEA,TAS --
GO:0006468 protein phosphorylation IEA --
GO:0008283 cell proliferation IMP 18541534
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress IMP 18541534
genes like me logo Genes that share ontologies with PDK1: view

Drugs & Compounds for PDK1 Gene

(24) Drugs for PDK1 Gene - From: DrugBank, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
4-[(3-CHLORO-4-{[(2R)-3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPANOYL]AMINO}PHENYL)SULFONYL]-N,N-DIMETHYLBENZAMIDE Experimental Pharma Target 0
Dichloroacetic Acid Experimental Pharma Target, inhibitor 0
AZD7545 Pharma PDHK inhibitor,potent and selective 0
BX517(PDK1 inhibitor2) Pharma PDK1 inhibitor 0

(9) Additional Compounds for PDK1 Gene - From: Novoseek and HMDB

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

(7) ApexBio Compounds for PDK1 Gene

Compound Action Cas Number
AZD7545 PDHK inhibitor,potent and selective 252017-04-2
BX517(PDK1 inhibitor2) PDK1 inhibitor 850717-64-5
BX795 PDK1 inhibitor 702675-74-9
GSK2334470 PDK1 inhibitor,highly specific and potent 1227911-45-6
NVP-BAG956 PI3K and PDK1 inhibitor 853910-02-8
PDK1 inhibitor PDK1 inhibitor 1001409-50-2
PS 48 1180676-32-7
genes like me logo Genes that share compounds with PDK1: view

Transcripts for PDK1 Gene

Unigene Clusters for PDK1 Gene

Pyruvate dehydrogenase kinase, isozyme 1:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for PDK1 Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10a · 10b · 10c ^ 11 ^ 12 ^ 13a · 13b · 13c · 13d ^ 14
SP1: - - -
SP2: -
SP3: - -
SP4: - - -
SP5: - - -
SP6: - - - - -
SP7: - - - -
SP8:

Relevant External Links for PDK1 Gene

GeneLoc Exon Structure for
PDK1
ECgene alternative splicing isoforms for
PDK1

Expression for PDK1 Gene

mRNA expression in normal human tissues for PDK1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PDK1 Gene

This gene is overexpressed in Stomach (14.0), Peripheral blood mononuclear cells (13.4), and Fetal heart (12.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for PDK1 Gene



Protein tissue co-expression partners for PDK1 Gene

NURSA nuclear receptor signaling pathways regulating expression of PDK1 Gene:

PDK1

SOURCE GeneReport for Unigene cluster for PDK1 Gene:

Hs.470633

mRNA Expression by UniProt/SwissProt for PDK1 Gene:

Q15118-PDK1_HUMAN
Tissue specificity: Expressed predominantly in the heart. Detected at lower levels in liver, skeletal muscle and pancreas.
genes like me logo Genes that share expression patterns with PDK1: view

Primer Products

No data available for mRNA differential expression in normal tissues for PDK1 Gene

Orthologs for PDK1 Gene

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

Orthologs for PDK1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PDK1 34 35
  • 99.63 (n)
dog
(Canis familiaris)
Mammalia -- 35
  • 97 (a)
OneToMany
-- 35
  • 95 (a)
OneToMany
PDK1 34
  • 93.06 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia PDK1 35
  • 94 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia -- 35
  • 93 (a)
OneToMany
-- 35
  • 92 (a)
OneToMany
-- 35
  • 91 (a)
OneToMany
cow
(Bos Taurus)
Mammalia PDK1 34 35
  • 92.13 (n)
rat
(Rattus norvegicus)
Mammalia Pdk1 34
  • 87.79 (n)
mouse
(Mus musculus)
Mammalia Pdk1 34 16 35
  • 86.64 (n)
chicken
(Gallus gallus)
Aves PDK1 34 35
  • 82.23 (n)
lizard
(Anolis carolinensis)
Reptilia PDK1 35
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia pdk1 34
  • 76.2 (n)
zebrafish
(Danio rerio)
Actinopterygii pdk1 34 35
  • 72.63 (n)
fruit fly
(Drosophila melanogaster)
Insecta Pdk 36 35
  • 56 (a)
worm
(Caenorhabditis elegans)
Secernentea ZK370.5 36
  • 50 (a)
pdhk-2 35
  • 48 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PKP1 35
  • 24 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3938 35
  • 47 (a)
OneToMany
Species where no ortholog for PDK1 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)
  • wheat (Triticum aestivum)

Evolution for PDK1 Gene

ENSEMBL:
Gene Tree for PDK1 (if available)
TreeFam:
Gene Tree for PDK1 (if available)

Paralogs for PDK1 Gene

Paralogs for PDK1 Gene

(4) SIMAP similar genes for PDK1 Gene using alignment to 9 proteins:

Pseudogenes.org Pseudogenes for PDK1 Gene

genes like me logo Genes that share paralogs with PDK1: view

Variants for PDK1 Gene

Sequence variations from dbSNP and Humsavar for PDK1 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs10048692 -- 172,602,752(+) GCCTA(C/G)GGTTT intron-variant
rs10048707 -- 172,602,884(+) CCACC(A/C)ATTAA intron-variant
rs10048825 -- 172,603,310(+) GATAT(A/C)CAGGG intron-variant
rs1010752 -- 172,617,950(-) GTTTT(C/G)TAAGT intron-variant
rs10165935 -- 172,668,605(+) TTATG(A/G)CCTCT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for PDK1 Gene

Variant ID Type Subtype PubMed ID
esv2760591 CNV gain 21179565
nsv1072047 CNV deletion 25765185
nsv3035 CNV deletion 18451855
nsv583665 CNV gain 21841781

Variation tolerance for PDK1 Gene

Residual Variation Intolerance Score: 71.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.39; 27.30% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for PDK1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PDK1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PDK1 Gene

Disorders for PDK1 Gene

MalaCards: The human disease database

(1) MalaCards diseases for PDK1 Gene - From: GeneCards

Disorder Aliases PubMed IDs
chronic mountain sickness
- elite association - COSMIC cancer census association via MalaCards
Search PDK1 in MalaCards View complete list of genes associated with diseases

Relevant External Links for PDK1

Genetic Association Database (GAD)
PDK1
Human Genome Epidemiology (HuGE) Navigator
PDK1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
PDK1
genes like me logo Genes that share disorders with PDK1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PDK1 Gene

Publications for PDK1 Gene

  1. Diversity of the pyruvate dehydrogenase kinase gene family in humans. (PMID: 7499431) Gudi R. … Popov K.M. (J. Biol. Chem. 1995) 2 3 4 22 64
  2. Pyruvate dehydrogenase complex activity controls metabolic and malignant phenotype in cancer cells. (PMID: 18541534) McFate T. … Verma A. (J. Biol. Chem. 2008) 3 4 22 64
  3. Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. (PMID: 17683942) Kato M. … Chuang D.T. (Structure 2007) 3 4 22 64
  4. Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer. (PMID: 21763680) Lu C.W. … Tsai S.J. (Am. J. Pathol. 2011) 3 4 64
  5. Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism. (PMID: 22195962) Hitosugi T. … Chen J. (Mol. Cell 2011) 3 4 64

Products for PDK1 Gene

Sources for PDK1 Gene

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