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PDK4 pyruvate dehydrogenase kinase 4 [ Homo sapiens (human) ]

Gene ID: 5166, updated on 27-Dec-2024

Summary

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Official Symbol
PDK4provided by HGNC
Official Full Name
pyruvate dehydrogenase kinase 4provided by HGNC
Primary source
HGNC:HGNC:8812
See related
Ensembl:ENSG00000004799 MIM:602527; AllianceGenome:HGNC:8812
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
Summary
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]
Expression
Broad expression in fat (RPKM 319.9), adrenal (RPKM 136.4) and 18 other tissues See more
Orthologs
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Genomic context

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See PDK4 in Genome Data Viewer
Location:
7q21.3
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (95583499..95596516, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (96819655..96832673, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (95212811..95225828, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:95099762-95100961 Neighboring gene uncharacterized LOC107986823 Neighboring gene ankyrin repeat and SOCS box containing 4 Neighboring gene Sharpr-MPRA regulatory region 3033 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26294 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26295 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:95156819-95157320 Neighboring gene uncharacterized LOC124901699 Neighboring gene Sharpr-MPRA regulatory region 6047 Neighboring gene PDK4 antisense RNA 1 Neighboring gene VISTA enhancer hs1831 Neighboring gene VISTA enhancer hs2505 Neighboring gene uncharacterized LOC107986746

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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Related articles in PubMed

  1. Identification of differentially expressed genes and the role of PDK4 in CD14+ monocytes of coronary artery disease. Du P, et al. Biosci Rep, 2021 Apr 30. PMID 33739370, Free PMC Article
  2. Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts. Liu X, et al. Sci Rep, 2017 Aug 16. PMID 28814762, Free PMC Article
  3. Oncogenic role of PDK4 in human colon cancer cells. Leclerc D, et al. Br J Cancer, 2017 Mar 28. PMID 28208156, Free PMC Article
  4. Reduction of mitochondria and up regulation of pyruvate dehydrogenase kinase 4 of skeletal muscle in patients with chronic kidney disease. Xu C, et al. Nephrology (Carlton), 2020 Mar. PMID 31099942
  5. Increased Pyruvate Dehydrogenase Kinase 4 Expression in Lung Pericytes Is Associated with Reduced Endothelial-Pericyte Interactions and Small Vessel Loss in Pulmonary Arterial Hypertension. Yuan K, et al. Am J Pathol, 2016 Sep. PMID 27456128, Free PMC Article

See all (106) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Inhibition of Pyruvate Dehydrogenase Kinase 4 Attenuates Myocardial and Mitochondrial Injury in Sepsis-Induced Cardiomyopathy.
    Title: Inhibition of Pyruvate Dehydrogenase Kinase 4 Attenuates Myocardial and Mitochondrial Injury in Sepsis-Induced Cardiomyopathy.
  2. circFTO from M2 macrophage-derived small extracellular vesicles (sEV) enhances NSCLC malignancy by regulation miR-148a-3pPDK4 axis.
    Title: circFTO from M2 macrophage-derived small extracellular vesicles (sEV) enhances NSCLC malignancy by regulation miR-148a-3pPDK4 axis.
  3. Expression and Role of PDK4 on Childhood Dyslipidemia and Lipid Metabolism in Hyperlipidemic Mice.
    Title: Expression and Role of PDK4 on Childhood Dyslipidemia and Lipid Metabolism in Hyperlipidemic Mice.
  4. Identification of PDK4 as Hub Gene for Diabetic Nephropathy Using Co-Expression Network Analysis.
    Title: Identification of PDK4 as Hub Gene for Diabetic Nephropathy Using Co-Expression Network Analysis.
  5. High glucose promotes benign prostatic hyperplasia by downregulating PDK4 expression.
    Title: High glucose promotes benign prostatic hyperplasia by downregulating PDK4 expression.
  6. PDK4 facilitates fibroblast functions and diabetic wound healing through regulation of HIF-1alpha protein stability and gene expression.
    Title: PDK4 facilitates fibroblast functions and diabetic wound healing through regulation of HIF-1α protein stability and gene expression.
  7. Promotive role of eukaryotic translation initiation factor 4A isoform 3 in ovarian cancer cell growth and aerobic glycolysis through the pyruvate dehydrogenase kinase 4 signaling.
    Title: Promotive role of eukaryotic translation initiation factor 4A isoform 3 in ovarian cancer cell growth and aerobic glycolysis through the pyruvate dehydrogenase kinase 4 signaling.
  8. WTAP Mediated the N6-methyladenosine Modification of PDK4 to Regulate the Malignant Behaviors of Colorectal Cancer Cells In Vitro and In Vivo.
    Title: WTAP Mediated the N6-methyladenosine Modification of PDK4 to Regulate the Malignant Behaviors of Colorectal Cancer Cells In Vitro and In Vivo.
  9. Glucocorticoid Receptors Drive Breast Cancer Cell Migration and Metabolic Reprogramming via PDK4.
    Title: Glucocorticoid Receptors Drive Breast Cancer Cell Migration and Metabolic Reprogramming via PDK4.
  10. The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4.
    Title: The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4.
Submit: New GeneRIF Correction See all GeneRIFs (74)

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

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Vpr vpr HIV-1 Vpr enhances PPARbeta/delta-induced PDK4, carnitine palmitoyltransferase I (CPT1), and acetyl-coenzyme A acyltransferase 2 (ACAA2) mRNA expression in cells PubMed
vpr HIV-1 Vpr enhances PPARbeta/delta agonist GW501516-induced pyruvate dehydrogenase kinase 4 (PDK4) protein expression and phosphorylation of pyruvate dehydrogenase alpha 1 (PDHE1alpha) at serine 293 in cells PubMed
matrix gag HIV-1 MA increases PDK4 mRNA expression in HepG2 cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ40832

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 pyruvate dehydrogenase (acetyl-transferring) kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables pyruvate dehydrogenase (acetyl-transferring) kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in cellular response to fatty acid IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to starvation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in glucose homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in insulin receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in insulin receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of anoikis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in reactive oxygen species metabolic process 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 bone resorption IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of fatty acid biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of fatty acid oxidation ISS
Inferred from Sequence or Structural Similarity
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 ketone metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of pH ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in response to starvation ISS
Inferred from Sequence or Structural Similarity
more info
  
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
  

General protein information

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Preferred Names
pyruvate dehydrogenase kinase, isozyme 4
Names
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial
[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial
pyruvate dehydrogenase kinase, isoenzyme 4
pyruvate dehydrogenase, lipoamide, kinase isozyme 4, mitochondrial
NP_002603.1

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_047008.1 RefSeqGene

    Range
    5098..18115
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_002612.4 → NP_002603.1  pyruvate dehydrogenase kinase, isozyme 4

    See identical proteins and their annotated locations for NP_002603.1

    Status: REVIEWED

    Source sequence(s)
    AF334710, BC040239, DA923767, DB035430, U54617
    Consensus CDS
    CCDS5643.1
    UniProtKB/Swiss-Prot
    Q16654
    UniProtKB/TrEMBL
    A4D1H4, Q53FG1
    Related
    ENSP00000005178.5, ENST00000005178.6
    Conserved Domains (2) summary
    smart00387
    Location:245 → 365
    HATPase_c; Histidine kinase-like ATPases
    pfam10436
    Location:34 → 195
    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_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    95583499..95596516 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    96819655..96832673 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q16654.1 GenPept UniProtKB/Swiss-Prot:Q16654

Gene LinkOut

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