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    PDK4 pyruvate dehydrogenase kinase, isozyme 4 [ Homo sapiens ]

    Gene ID: 5166, updated on 11-May-2012
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    Summary

    Official Symbol
    PDK4provided by HGNC
    Official Full Name
    pyruvate dehydrogenase kinase, isozyme 4provided by HGNC
    Primary source
    HGNC:8812
    See related
    Ensembl:ENSG00000004799; HPRD:03957; MIM:602527; Vega:OTTHUMG00000153977
    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
    FLJ40832
    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]
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    Genomic context

    Location :
    7q21.3
    Sequence :
    Chromosome: 7; NC_000007.13 (95212809..95225925, complement)
    See PDK4 in Epigenomics, MapViewer

    Chromosome 7 - NC_000007.13Genomic Context describing neighboring genes Neighboring gene paraoxonase 2 Neighboring gene ankyrin repeat and SOCS box containing 4 Neighboring gene dynein, cytoplasmic 1, intermediate chain 1 Neighboring gene solute carrier family 25 (aspartate/glutamate carrier), member 13 Neighboring gene cytochrome c, somatic pseudogene 18

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    2. Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4. Kukimoto-Niino M, et al. Acta Crystallogr D Biol Crystallogr, 2011 Sep. PMID 21904029.
    3. Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation. Grassian AR, et al. Genes Dev, 2011 Aug 15. PMID 21852536.
    4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. Hendrickson SL, et al. PLoS One, 2010 Sep 21. PMID 20877624.
    5. Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex. Blouin JM, et al. Int J Cancer, 2011 Jun 1. PMID 20715114.

    See all (42) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. The present structures demonstrate the flexible and dynamic aspects of PDK4 in the open conformation and provide a basis for the development of novel inhibitors targeting the nucleotide-binding pocket of PDK4.
      Title: Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4.
    2. Data show that overexpression of ErbB2 maintains PDH flux by suppressing PDK4 expression in an Erk-dependent manner.
      Title: Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation.
    3. PDK4 gene is downregulated in colic adenocarcinoma.
      Title: Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex.
    4. PDK4 with bound ADP exists in equilibrium between the open and the closed conformations
      Title: Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity.
    5. PDK4 upregulation in adipocytes participates in the hypolipidemic effect of thiazolidinediones through modulation of glyceroneogenesis
      Title: Pyruvate dehydrogenase kinase 4: regulation by thiazolidinediones and implication in glyceroneogenesis in adipose tissue.
    6. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    7. Observational study of genotype prevalence and gene-disease association. (HuGE Navigator)
      Title: [Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal].
    8. Accumulation of im lipids plays a more important role than impaired activation of Akt-mediated pathways in the regulation of muscle PDK4 gene expression in lipid-induced acute insulin-resistant states
      Title: Elevated free fatty acids attenuate the insulin-induced suppression of PDK4 gene expression in human skeletal muscle: potential role of intramuscular long-chain acyl-coenzyme A.
    9. PDK2, PDK3 and PDK4 are primary PPARbeta/delta target genes in humans underlining the importance of the receptor in the control of metabolism
      Title: Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta.
    10. Gene expression regulation is affected by retinoic acid and histone acetyation (review).
      Title: Mechanisms responsible for regulation of pyruvate dehydrogenase kinase 4 gene expression.
    Submit: New GeneRIF Correction See all (17)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q16654 P10515 DLAT    HPRD  PubMed  
    Q16654 P08559 PDHA1    HPRD  PubMed  
    Q16654 Q16654 PDK4    HPRD  PubMed  
    BioGRID:111192 BioGRID:124195 TRIM63    BioGRID  PubMed Two-hybrid 
    BioGRID:111192 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Co-purification 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Pyruvate metabolism, organism-specific biosystem (from REACTOME)
      Pyruvate metabolism, organism-specific biosystemPyruvate sits at an intersection of key pathways of energy metabolism. It is the end product of glycolysis and the starting point for gluconeogenesis, and can be generated by transamination of alanin...
    • Pyruvate metabolism and Citric Acid (TCA) cycle, organism-specific biosystem (from REACTOME)
      Pyruvate metabolism and Citric Acid (TCA) cycle, organism-specific biosystemPyruvate metabolism and the citric acid (TCA) cycle together link the processes of energy metabolism in a human cell with one another and with key biosynthetic reactions. Pyruvate, derived from the r...
    • Regulation of pyruvate dehydrogenase (PDH) complex, organism-specific biosystem (from REACTOME)
      Regulation of pyruvate dehydrogenase (PDH) complex, organism-specific biosystemThe mitochondrial pyruvate dehydrogenase (PDH) complex catalyzes the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid synthesis. PDH inactivati...
    • TCA Cycle, organism-specific biosystem (from WikiPathways)
      TCA Cycle, organism-specific biosystemThe [[wikipedia:citric_acid_cycle|citric acid cycle]], also known as the tricarboxylic acid cycle (TCA cycle) or the Krebs cycle, (or rarely, the Szent-Gyorgyi-Krebs cycle) is a series of enzyme-cata...
    • The citric acid (TCA) cycle and respiratory electron transport, organism-specific biosystem (from REACTOME)
      The citric acid (TCA) cycle and respiratory electron transport, organism-specific biosystemThe metabolism of pyruvate provides one source of acetyl-CoA which enters the citric acid (TCA, tricarboxylic acid) cycle to generate energy and the reducing equivalent NADH. These reducing equivalen...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    pyruvate dehydrogenase (acetyl-transferring) kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    two-component sensor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    carbohydrate metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    glucose metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    peptidyl-histidine phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein phosphorylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    pyruvate metabolic process TAS
    Traceable Author Statement
    more info
    		  
    regulation of acetyl-CoA biosynthetic process from pyruvate TAS
    Traceable Author Statement
    more info
    		  
    small molecule metabolic process TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    mitochondrial inner membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    pyruvate dehydrogenase kinase, isozyme 4
    Names
    pyruvate dehydrogenase kinase, isozyme 4
    pyruvate dehydrogenase kinase, isoenzyme 4
    pyruvate dehydrogenase, lipoamide, kinase isozyme 4, mitochondrial
    [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial
    NP_002603.1
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    NCBI Reference Sequences (RefSeq)

    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.

    mRNA and Protein(s)

    1. NM_002612.3 → NP_002603.1  pyruvate dehydrogenase kinase, isozyme 4

      Status: REVIEWED

      Source sequence(s)
      AF334710, BC040239, DA923767, DB035430, U54617
      Consensus CDS
      CCDS5643.1
      UniProtKB/TrEMBL
      A4D1H4
      UniProtKB/Swiss-Prot
      Q16654
      Related
      ENSP00000005178, OTTHUMP00000204768, ENST00000005178, OTTHUMT00000333298
      Conserved Domains (2) summary
      cd00075
      Location:248 – 364
      Blast Score: 182
      HATPase_c; Histidine kinase-like ATPases; This family includes several ATP-binding proteins for example: histidine kinase, DNA gyrase B, topoisomerases, heat shock protein HSP90, phytochrome-like ATPases and DNA mismatch repair proteins
      pfam10436
      Location:33 – 196
      Blast Score: 515
      BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000007.13 Reference GRCh37.p5 Primary Assembly

      Range
      95212809..95225925, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000139.1 Alternate HuRef

      Range
      89819915..89833034, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CRA_TCAGchr7v2

    Genomic

    1. AC_000068.1 Alternate CRA_TCAGchr7v2

      Range
      94541818..94554938, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC002451.1 AAB67048.1
    genomic CH236949.1 EAL24127.1
      EAL24128.1
    genomic CH236949.1 EAL24127.1
      EAL24128.1
    genomic CH471091.2 EAW76757.1
      EAW76758.1
      EAW76759.1
    genomic U54618.1 AAC50670.1
    genomic U54619.1 AAC50670.1
    genomic U54620.1 AAC50670.1
    genomic U54621.1 AAC50670.1
    genomic U54622.1 AAC50670.1
    genomic U54623.1 AAC50670.1
    genomic U54624.1 AAC50670.1
    genomic U54625.1 AAC50670.1
    genomic U54626.1 AAC50670.1
    genomic U54627.1 AAC50670.1
    genomic U54628.1 AAC50670.1
    mRNA AF334710.1 None
    mRNA AK096428.1 BAG53287.1
    mRNA AK098151.1 BAG53583.1
    mRNA AK223328.1 BAD97048.1
    mRNA AK312424.1 BAG35334.1
    mRNA BC040239.1 AAH40239.1
    mRNA DA923767.1 None
    mRNA DB035430.1 None
    mRNA U54617.1 AAC50669.1
    other-genetic DQ891256.2 ABM82182.1
    other-genetic DQ894441.2 ABM85367.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q16654.1 GenPept UniProtKB/Swiss-Prot:Q16654
    Q53FG1 GenPept UniProtKB/TrEMBL:Q53FG1
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
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