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PDK3 pyruvate dehydrogenase kinase 3 [ Homo sapiens (human) ]

Gene ID: 5165, updated on 5-Mar-2024

Summary

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Official Symbol
PDK3provided by HGNC
Official Full Name
pyruvate dehydrogenase kinase 3provided by HGNC
Primary source
HGNC:HGNC:8811
See related
Ensembl:ENSG00000067992 MIM:300906; AllianceGenome:HGNC:8811
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CMTX6; GS1-358P8.4
Summary
The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle, and thus is one of the major enzymes responsible for the regulation of glucose metabolism. The enzymatic activity of PDH is regulated by a phosphorylation/dephosphorylation cycle, and phosphorylation results in inactivation of PDH. The protein encoded by this gene is one of the three pyruvate dehydrogenase kinases that inhibits the PDH complex by phosphorylation of the E1 alpha subunit. This gene is predominantly expressed in the heart and skeletal muscles. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
Expression
Ubiquitous expression in brain (RPKM 5.9), testis (RPKM 4.2) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
Xp22.11
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (24465286..24550466)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (24049577..24134762)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (24483403..24568583)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:24382719-24383459 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chrX:24389623-24390398 Neighboring gene SUPT20H like 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:24394111-24394637 Neighboring gene NANOG hESC enhancer GRCh37_chrX:24428490-24429048 Neighboring gene ribosomal protein S26 pseudogene 58 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20719 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:24509351-24510314 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29505 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:24546061-24546668 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:24546669-24547275 Neighboring gene SNRPE pseudogene 9 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20720 Neighboring gene phosphate cytidylyltransferase 1B, choline Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29506 Neighboring gene PCYT1B antisense RNA 1 Neighboring gene H2B histone pseudogene 7

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Charcot-Marie-tooth disease causing mutation (p.R158H) in pyruvate dehydrogenase kinase 3 (PDK3) affects synaptic transmission, ATP production and causes neurodegeneration in a CMTX6 C. elegans model. Narayanan RK, et al. Hum Mol Genet, 2021 Dec 17. PMID 34387338, Free PMC Article
  2. Energy metabolism and mitochondrial defects in X-linked Charcot-Marie-Tooth (CMTX6) iPSC-derived motor neurons with the p.R158H PDK3 mutation. Perez-Siles G, et al. Sci Rep, 2020 Jun 5. PMID 32504000, Free PMC Article
  3. Effect of pH on the structure and function of pyruvate dehydrogenase kinase 3: Combined spectroscopic and MD simulation studies. Anwar S, et al. Int J Biol Macromol, 2020 Mar 15. PMID 31982536
  4. X-linked Charcot-Marie-Tooth disease type 6 (CMTX6) patients with a p.R158H mutation in the pyruvate dehydrogenase kinase isoenzyme 3 gene. Kennerson ML, et al. J Peripher Nerv Syst, 2016 Mar. PMID 26801680
  5. A new locus for X-linked dominant Charcot-Marie-Tooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene. Kennerson ML, et al. Hum Mol Genet, 2013 Apr 1. PMID 23297365, Free PMC Article

See all (72) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Unveiling the clinical and electrophysiological profile of CMTX6: Insights from two Brazilian families.
    Title: Unveiling the clinical and electrophysiological profile of CMTX6: Insights from two Brazilian families.
  2. Charcot-Marie-tooth disease causing mutation (p.R158H) in pyruvate dehydrogenase kinase 3 (PDK3) affects synaptic transmission, ATP production and causes neurodegeneration in a CMTX6 C. elegans model.
    Title: Charcot-Marie-tooth disease causing mutation (p.R158H) in pyruvate dehydrogenase kinase 3 (PDK3) affects synaptic transmission, ATP production and causes neurodegeneration in a CMTX6 C. elegans model.
  3. Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia.
    Title: Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia.
  4. Energy metabolism and mitochondrial defects in X-linked Charcot-Marie-Tooth (CMTX6) iPSC-derived motor neurons with the p.R158H PDK3 mutation.
    Title: Energy metabolism and mitochondrial defects in X-linked Charcot-Marie-Tooth (CMTX6) iPSC-derived motor neurons with the p.R158H PDK3 mutation.
  5. Effect of pH on the structure and function of pyruvate dehydrogenase kinase 3: Combined spectroscopic and MD simulation studies.
    Title: Effect of pH on the structure and function of pyruvate dehydrogenase kinase 3: Combined spectroscopic and MD simulation studies.
  6. miR-497-5p inhibits gastric cancer cell proliferation and growth through targeting PDK3.
    Title: miR-497-5p inhibits gastric cancer cell proliferation and growth through targeting PDK3.
  7. PDK3 forms a positive feedback loop with HSF1 to drive glycolysis in chemoresistance.
    Title: Metabolic enzyme PDK3 forms a positive feedback loop with transcription factor HSF1 to drive chemoresistance.
  8. The pyruvate dehydrogenase kinases (PDKs) PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial oxidation.
    Title: KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis.
  9. We have identified a p.R158H PDK3 mutation in a Korean X-linked dominant Charcot-Marie-Tooth type 6 family
    Title: X-linked Charcot-Marie-Tooth disease type 6 (CMTX6) patients with a p.R158H mutation in the pyruvate dehydrogenase kinase isoenzyme 3 gene.
  10. Accordingly, elevated levels of PDK1, PDK3, and PKM2 and reduced PK activity could be observed in iPSCs and human embryonic stem cells in the undifferentiated state
    Title: HIF1α modulates cell fate reprogramming through early glycolytic shift and upregulation of PDK1-3 and PKM2.
Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Charcot-Marie-Tooth disease X-linked dominant 6
MedGen: C3806702 OMIM: 300905 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables pyruvate dehydrogenase (acetyl-transferring) kinase activity EXP
Inferred from Experiment
more info
 PubMed 
enables pyruvate dehydrogenase (acetyl-transferring) kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables pyruvate dehydrogenase (acetyl-transferring) kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in cellular response to fatty acid IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in hypoxia-inducible factor-1alpha signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in peroxisome proliferator activated receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of acetyl-CoA biosynthetic process from pyruvate IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of acetyl-CoA biosynthetic process from pyruvate TAS
Traceable Author Statement
more info
  
involved_in regulation of glucose metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of glucose metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of reactive oxygen species metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  
located_in nucleolus IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
pyruvate dehydrogenase kinase, isozyme 3
Names
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial
pyruvate dehydrogenase kinase, isoenzyme 3
pyruvate dehydrogenase, lipoamide, kinase isozyme 3, mitochondrial
NP_001135858.1
NP_005382.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_016762.1 RefSeqGene

    Range
    5060..74196
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001142386.3 → NP_001135858.1  pyruvate dehydrogenase kinase, isozyme 3 isoform 1 precursor

    See identical proteins and their annotated locations for NP_001135858.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AC004656, AI001064, AK301965, BC038512, BI549903, BU069975
    Consensus CDS
    CCDS48088.1
    UniProtKB/Swiss-Prot
    Q15120
    Related
    ENSP00000498864.1, ENST00000568479.2
    Conserved Domains (2) summary
    cd16929
    Location:192 → 359
    HATPase_PDK-like; Histidine kinase-like ATPase domain of pyruvate dehydrogenase kinase, branched-chain alpha-ketoacid dehydrogenase kinase and related domains
    pfam10436
    Location:26 → 188
    BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase

  2. NM_005391.5 → NP_005382.1  pyruvate dehydrogenase kinase, isozyme 3 isoform 2 precursor

    See identical proteins and their annotated locations for NP_005382.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs at the 3' end compared to variant 1, resulting in a shorter isoform (2) lacking the last 9 aa from the C-terminus, compared to isoform 1.
    Source sequence(s)
    AC004656, BC015948, BI549903, L42452
    Consensus CDS
    CCDS14212.1
    UniProtKB/Swiss-Prot
    B4DXG6, Q15120
    Related
    ENSP00000368460.4, ENST00000379162.9
    Conserved Domains (2) summary
    smart00387
    Location:238 → 359
    HATPase_c; Histidine kinase-like ATPases
    pfam10436
    Location:26 → 188
    BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    24465286..24550466
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    24049577..24134762
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q15120.1 GenPept UniProtKB/Swiss-Prot:Q15120

Gene LinkOut

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