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

    Gene ID: 5165, updated on 9-Dec-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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    See PDK3 in Genome Data Viewer
    Location:
    Xp22.11
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (24465286..24550466)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (24049577..24134762)
    RS_2024_09 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. Unveiling the clinical and electrophysiological profile of CMTX6: Insights from two Brazilian families. Maciel VAZ, et al. J Peripher Nerv Syst, 2023 Dec. PMID 37849068
    2. Structural determinants for cross-talk between pyruvate dehydrogenase kinase 3 and lipoyl domain 2 of the human pyruvate dehydrogenase complex. Tso SC, et al. J Biol Chem, 2006 Sep 15. PMID 16849321
    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. Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications. Devedjiev Y, et al. J Mol Biol, 2007 Jul 13. PMID 17532006, Free PMC Article
    5. 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

    See all (78) 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
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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 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 regulation of acetyl-CoA biosynthetic process from pyruvate 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 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
    		  
    located_in mitochondrion HTP PubMed 
    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_2024_08

    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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