My NCBISign In

Display Settings:

Format

Send to:

Choose Destination

    PDK3 pyruvate dehydrogenase kinase, isozyme 3 [ Homo sapiens ]

    Gene ID: 5165, updated on 11-May-2012
    Help top of page

    Summary

    Official Symbol
    PDK3provided by HGNC
    Official Full Name
    pyruvate dehydrogenase kinase, isozyme 3provided by HGNC
    Primary source
    HGNC:8811
    See related
    Ensembl:ENSG00000067992; HPRD:03956; MIM:602526; Vega:OTTHUMG00000021269
    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
    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]
    Help top of page

    Genomic context

    Location :
    Xp22.11
    Sequence :
    Chromosome: X; NC_000023.10 (24483344..24568583)
    See PDK3 in Epigenomics, MapViewer

    Chromosome X - NC_000023.10Genomic Context describing neighboring genes Neighboring gene family with sequence similarity 48, member B1 Neighboring gene ribosomal protein S26 pseudogene 58 Neighboring gene phosphate cytidylyltransferase 1, choline, beta Neighboring gene ribosomal protein L23 pseudogene

    Help top of page

    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
    Helptop of page

    Bibliography

    Related articles in PubMed

    1. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Wagner SA, et al. Mol Cell Proteomics, 2011 Oct. PMID 21890473.
    2. A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. Richter R, et al. EMBO J, 2010 Mar 17. PMID 20186120.
    3. Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Deribe YL, et al. Sci Signal, 2009 Dec 22. PMID 20029029.
    4. Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance. Lu CW, et al. J Biol Chem, 2008 Oct 17. PMID 18718909.
    5. Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Kato M, et al. Structure, 2007 Aug. PMID 17683942.

    See all (20) 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. increased PDK3 expression due to elevated HIF-1alpha in cancer cells may play critical roles in metabolic switch during cancer progression and chemoresistance in cancer therapy
      Title: Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance.
    2. Distinct structural mechanisms for inhibition of PDK3 by AZD7545, dichloroacetate, and radicol.
      Title: Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol.
    3. 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.
    4. crystal structure of the asymmetric PDHK3/lipoyl domain 2 complex; data suggest that the asymmetric complex represents a physiological state in which binding of a single L2-domain activates one of the PDHK protomers while inactivating another
      Title: Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications.
    5. analysis of residues in L2 and residues in the C-terminal region and the lipoyl-binding pocket of PDK3 which are critical determinants for the cross-talk between L2 and PDK3, which up-regulates PDK3 activity
      Title: Structural determinants for cross-talk between pyruvate dehydrogenase kinase 3 and lipoyl domain 2 of the human pyruvate dehydrogenase complex.
    6. mRNA levels not changed in skeletal muscle during fasting
      Title: Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting.
    Submit: New GeneRIF Correction
    Help top of page

    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Help top of page

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_005382.1 NP_000275.1 PDHA1    BIND  PubMed PDK3 interacts with and phosphorylates PDHA1 (E1p). 
    Q15120 P10515 DLAT    HPRD  PubMed  
    Q15120 P08559 PDHA1    HPRD  PubMed  
    BioGRID:111191 BioGRID:108081 DLAT    BioGRID  PubMed Reconstituted Complex 
    BioGRID:111191 BioGRID:108276 EGFR    BioGRID  PubMed PCA 
    BioGRID:111191 BioGRID:109622 ICT1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111191 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    Help top of page

    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 binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    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 matrix TAS
    Traceable Author Statement
    more info
    		  
    mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    Help top of page

    General protein information

    Preferred Names
    pyruvate dehydrogenase kinase, isozyme 3
    Names
    pyruvate dehydrogenase kinase, isozyme 3
    pyruvate dehydrogenase kinase, isoenzyme 3
    pyruvate dehydrogenase, lipoamide, kinase isozyme 3, mitochondrial
    NP_001135858.1
    NP_005382.1
    Help top of page

    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.

    Genomic

    1. NG_016762.1 RefSeqGene

      Range
      5001..90240
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001142386.2 → NP_001135858.1  pyruvate dehydrogenase kinase, isozyme 3 isoform 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
      Related
      ENSP00000387536, OTTHUMP00000226873, ENST00000441463, OTTHUMT00000056099
      Conserved Domains (2) summary
      cd00075
      Location:241 – 358
      Blast Score: 162
      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:25 – 189
      Blast Score: 559
      BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase

    2. NM_005391.4 → NP_005382.1  pyruvate dehydrogenase kinase, isozyme 3 isoform 2

      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
      Q15120
      Related
      ENSP00000368460, OTTHUMP00000023083, ENST00000379162, OTTHUMT00000056097
      Conserved Domains (2) summary
      cd00075
      Location:241 – 358
      Blast Score: 163
      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:25 – 189
      Blast Score: 559
      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_000023.10 Reference GRCh37.p5 Primary Assembly

      Range
      24483344..24568583
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000155.1 Alternate HuRef

      Range
      22225142..22310559
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Help top of page

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC004552.1 (120572..137270) None
    genomic AC004656.1 (206..52495) None
    genomic CH471074.1 EAW99019.1
      EAW99020.1
    mRNA AI001064.1 None
    mRNA AI080664.1 None
    mRNA AK301965.1 BAG63378.1
    mRNA AW173304.1 None
    mRNA BC015948.1 AAH15948.1
    mRNA BC038512.2 None
    mRNA BG717206.1 None
    mRNA BI549903.1 None
    mRNA BU069975.1 None
    mRNA L42452.1 AAC42011.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q15120.1 GenPept UniProtKB/Swiss-Prot:Q15120
    Help top of page

    Additional Links

    Additional Links

    Gene LinkOut

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

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Links

      Links to other resources

      General information

      Related sites

      Feedback

      Subscription

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...