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PDK4 Gene

protein-coding   GIFtS: 64
GCID: GC07M095212

Pyruvate Dehydrogenase Kinase, Isozyme 4

(Previous names: pyruvate dehydrogenase kinase, isoenzyme 4)
  Search for PDK4
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Pyruvate Dehydrogenase Kinase, Isozyme 41 2     Pyruvate Dehydrogenase, Lipoamide, Kinase Isozyme 4, Mitochondrial2
Pyruvate Dehydrogenase Kinase, Isoenzyme 41 2     PDHK43
EC 2.7.11.23 8     Pyruvate Dehydrogenase Kinase Isoform 43
[Pyruvate Dehydrogenase (Acetyl-Transferring)] Kinase Isozyme 4,
Mitochondrial2
     EC 2.7.118
[Pyruvate Dehydrogenase [Lipoamide]] Kinase Isozyme 4, Mitochondrial2     

External Ids:    HGNC: 88121   Entrez Gene: 51662   Ensembl: ENSG000000047997   OMIM: 6025275   UniProtKB: Q166543   

Export aliases for PDK4 gene to outside databases

Previous GC identifers: GC07M093748 GC07M094811 GC07M094826 GC07M094824 GC07M094857 GC07M095050 GC07M089819


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for PDK4 Gene:
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)

GeneCards Summary for PDK4 Gene:
PDK4 (pyruvate dehydrogenase kinase, isozyme 4) is a protein-coding gene. GO annotations related to this gene include protein serine/threonine kinase activity and pyruvate dehydrogenase (acetyl-transferring) kinase activity. An important paralog of this gene is BCKDK.

UniProtKB/Swiss-Prot: PDK4_HUMAN, Q16654
Function: Serine/threonine kinase that plays a key role in regulation of glucose and fatty acid metabolism and
homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate
dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle,
down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of
pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged
fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and
is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an
important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under
starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates
both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen
species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in
regulating carbohydrate and fatty acid metabolism

Gene Wiki entry for PDK4 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000007.14  NC_018918.2  NT_007933.16  
Regulatory elements:
   Regulatory transcription factor binding sites in the PDK4 gene promoter:
         MEF-2A   PPAR-alpha   RFX1   HNF-1   MyoD   STAT5A   HNF-1A   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): PDK4 promoter sequence
   Search Chromatin IP Primers for PDK4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat PDK4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7q21.3   Ensembl cytogenetic band:  7q21.3   HGNC cytogenetic band: 7q21.3-q22.1

PDK4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PDK4 gene location

GeneLoc information about chromosome 7         GeneLoc Exon Structure

GeneLoc location for GC07M095212:  view genomic region     (about GC identifiers)

Start:
95,212,809 bp from pter      End:
95,225,925 bp from pter
Size:
13,117 bases      Orientation:
minus strand

1 alternative location:
Chr7-,CRA_TCAG 94,541,818-94,554,938     

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: PDK4_HUMAN, Q16654 (See protein sequence)
Recommended Name: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial precursor  
Size: 411 amino acids; 46469 Da
Subunit: Homodimer. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric
pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide
acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3)
5 PDB 3D structures from and Proteopedia for PDK4:
2E0A (3D)        2ZDX (3D)        2ZDY (3D)        2ZKJ (3D)        3D2R (3D)    

Explore the universe of human proteins at neXtProt for PDK4: NX_Q16654

Explore proteomics data for PDK4 at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for PDK4 (Q16654) (see all 12)
     VYVPSHL  HIGSIDP  IYLKALS  KNAMRAT 


    See PDK4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_002603.1  
    ENSEMBL proteins: 
     ENSP00000005178  
    Reactome Protein details: Q16654

    PDK4 Human Recombinant Protein Products:

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    Novus Biologicals PDK4 Proteins
    Novus Biologicals PDK4 Lysates
    Sino Biological Recombinant Protein for PDK4
    Sino Biological Cell Lysate for PDK4
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    Cloud-Clone Corp. Proteins for PDK4

     
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    Search eBioscience for ELISAs for PDK4 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: pyruvate dehydrogenase kinase, isozyme 4
    PDHK family

    3 InterPro protein domains:
     IPR005467 Sig_transdc_His_kinase_core
     IPR003594 HATPase_ATP-bd
     IPR018955 BCDHK/PDK_N

    Graphical View of Domain Structure for InterPro Entry Q16654

    ProtoNet protein and cluster: Q16654

    1 Blocks protein domain: IPB003594 ATP-binding region

    UniProtKB/Swiss-Prot: PDK4_HUMAN, Q16654
    Similarity: Belongs to the PDK/BCKDK protein kinase family
    Similarity: Contains 1 histidine kinase domain


    Find genes that share domains with PDK4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: PDK4_HUMAN, Q16654
    Function: Serine/threonine kinase that plays a key role in regulation of glucose and fatty acid metabolism and
    homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate
    dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle,
    down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of
    pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged
    fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and
    is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an
    important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under
    starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates
    both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen
    species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in
    regulating carbohydrate and fatty acid metabolism
    Catalytic activity: ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase
    (acetyl-transferring)] phosphate
    Induction: Up-regulated by prolonged fasting, in glucose-deprived cells and in response to a high-fat diet.
    Down-regulated by insulin. Up-regulated by PPARD

         Genatlas biochemistry entry for PDK4:
    pyruvate dehydrogenase kinase 4,highly expressed in heart and skeletal muscle,regulating mitochondrial PDH
    activity

         Enzyme Numbers (IUBMB): EC 2.7.11.21 2 EC 2.7.112

         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity IDA18658136
    GO:0004674protein serine/threonine kinase activity IEA--
    GO:0004740pyruvate dehydrogenase (acetyl-transferring) kinase activity ISS--
    GO:0005524ATP binding IDA18658136
         
    Find genes that share ontologies with PDK4           About GenesLikeMe


    Phenotypes:
         3 GenomeRNAi human phenotypes for PDK4:
     Decreased substrate adherent c  Increased S DNA content  Increased cell death HMECs cel 

         5 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Pdk4):
     cellular  hematopoietic system  homeostasis/metabolism  immune system  skeleton 

    Find genes that share phenotypes with PDK4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for PDK4: Pdk4tm1Rhar Pdk4tm1Tok

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for PDK4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for PDK4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for PDK4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for PDK4

    miRNA
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    miRTarBase miRNAs that target PDK4:
    hsa-mir-16-5p (MIRT032003), hsa-mir-26b-5p (MIRT030098), hsa-mir-103a-3p (MIRT027229), hsa-mir-335-5p (MIRT018910)

    Block miRNA regulation of human, mouse, rat PDK4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate PDK4 (see all 37):
    hsa-miR-361-5p hsa-miR-640 hsa-miR-15a hsa-miR-29a hsa-miR-500a hsa-miR-374a* hsa-miR-9 hsa-miR-424
    SwitchGear 3'UTR luciferase reporter plasmidPDK4 3' UTR sequence
    Inhib. RNA
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    OriGene RNAi products in human, mouse, rat for PDK4
    Predesigned siRNA for gene silencing in human, mouse, rat PDK4

    Gene Editing
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    Clone
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    OriGene clones in human, mouse for PDK4 (see all 6)
    OriGene ORF clones in mouse, rat for PDK4
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PDK4
    Addgene plasmids for PDK4 

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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PDK4


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    PDK4_HUMAN, Q16654: Mitochondrion matrix
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    mitochondrion5
    cytosol1
    nucleus1

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005739mitochondrion TAS8798399
    GO:0005743mitochondrial inner membrane IEA--
    GO:0005759mitochondrial matrix TAS--

    Find genes that share ontologies with PDK4           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for PDK4 About    
    See pathways by source

    SuperPathContained pathways About
    1Citric acid cycle (TCA cycle)
    Pyruvate metabolism and Citric Acid (TCA) cycle0.49
    Pyruvate metabolism0.00
    Regulation of pyruvate dehydrogenase (PDH) complex0.00
    2Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.
    The citric acid (TCA) cycle and respiratory electron transport0.71
    3Nanog in Mammalian ESC Pluripotency
    eNOS Signaling0.48
    4Metabolism
    Metabolism0.38


    Find genes that share SuperPaths with PDK4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for PDK4
        eNOS Signaling


    1 Reactome Pathway for PDK4
        Regulation of pyruvate dehydrogenase (PDH) complex


        Pathway & Disease-focused RT2 Profiler PCR Arrays including PDK4: 
              Skeletal Muscle: Myogenesis & Myopathy in human mouse rat
              Fatty Liver in human mouse rat
              Glucose Metabolism in human mouse rat
              Cardiotoxicity in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for PDK4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for PDK4 (Q166543 ENSP000000051784) via UniProtKB, MINT, STRING, and/or I2D (see all 81)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TRIM63Q969Q13, ENSP000003633904I2D: score=2 STRING: ENSP00000363390
    DLATP105153, ENSP000002803464I2D: score=1 STRING: ENSP00000280346
    PDHA1P085593, ENSP000003943824I2D: score=1 STRING: ENSP00000394382
    ACOX1Q150673I2D: score=3 
    BCKDKO148743I2D: score=3 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 19):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006006glucose metabolic process IEA--
    GO:0006090pyruvate metabolic process TAS--
    GO:0006468protein phosphorylation TAS8798399
    GO:0006885regulation of pH ISS--
    GO:0008286insulin receptor signaling pathway IMP--

    Find genes that share ontologies with PDK4           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for PDK4

    3 HMDB Compounds for PDK4    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    Hydrogen phosphateBiphosphate (see all 10)14066-19-4--

    1 DrugBank Compound for PDK4    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    4-[4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl]benzene-1,3-diol-- --target--10592235

    Selected Novoseek inferred chemical compound relationships for PDK4 gene (see all 12)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pyruvate 89.7 118 10905486 (3), 17079227 (3), 17062764 (2), 11485553 (2) (see all 65)
    fatty acid 67.9 22 18308721 (2), 15776585 (2), 11181544 (1), 12476789 (1) (see all 14)
    carnitine 62.1 9 16092055 (2), 19448714 (1), 14761878 (1), 20040361 (1) (see all 6)
    glucose 59.4 42 16314495 (4), 12582211 (2), 18308721 (2), 17132539 (2) (see all 24)
    glycogen 55.6 16 12015434 (3), 15294034 (2), 17488246 (1), 18468620 (1) (see all 8)
    lipid 47.9 13 17132539 (2), 12676647 (1), 15988707 (1), 17652214 (1) (see all 7)
    carbohydrates 35.4 1 15294034 (1)
    adp 10.7 2 18658136 (2)
    lactate 9.06 1 12676647 (1)
    estrogen 8.26 1 19703515 (1)



    Find genes that share compounds with PDK4           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for PDK4 gene: 
    NM_002612.3  

    Unigene Cluster for PDK4:

    Pyruvate dehydrogenase kinase, isozyme 4
    Hs.8364  [show with all ESTs]
    Unigene Representative Sequence: NM_002612
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000005178(uc003unz.3 uc003uoa.3) ENST00000473796 ENST00000468445
    ENST00000498190 ENST00000473301
    miRNA
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    hsa-miR-361-5p hsa-miR-640 hsa-miR-15a hsa-miR-29a hsa-miR-500a hsa-miR-374a* hsa-miR-9 hsa-miR-424
    SwitchGear 3'UTR luciferase reporter plasmidPDK4 3' UTR sequence
    Inhib. RNA
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    Addgene plasmids for PDK4 
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      QuantiTect SYBR Green Assays in human, mouse, rat PDK4
      QuantiFast Probe-based Assays in human, mouse, rat PDK4

    Additional mRNA sequence: 

    AF334710.1 AK096428.1 AK223328.1 AK312424.1 AL832708.1 BC040239.1 U54617.1 

    11 DOTS entries:

    DT.100796230  DT.91763218  DT.97783442  DT.87005165  DT.432654  DT.91828603  DT.92045984  DT.100651048 
    DT.100663881  DT.95307742  DT.100796231 

    Selected AceView cDNA sequences (see all 260):

    AI380785 AW058225 BF449008 AW149114 U54617 AW028855 CR590426 AI493814 
    AA294964 BM263195 AI304339 AA719031 AA310620 AI672326 AI174832 BX498918 
    AW057881 AW614301 BX480175 AI266683 AI273770 AA835089 AA046703 AF334710 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    PDK4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TAAATACTTG
    PDK4 Expression
    About this image


    PDK4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 19) fully expand
     
     Adipose (Muscoskeletal System)    fully expand to see all 6 entries
             Thoracic Perivascular Adipose
             White adipocyte-like cells
     
     Bone (Muscoskeletal System)    fully expand to see all 6 entries
             Bone Marrow
             HyStem+TGFbeta3+GDF5-induced MEL2 cells
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Cerebral Cortex
     
     Cartilage (Muscoskeletal System)    fully expand to see all 3 entries
             HyStem+TGFbeta3+GDF5-induced MEL2 cells
     
     Ovary (Reproductive System)    fully expand to see all 2 entries
             Pre-Granulosa Cells Primordial Follicle
             Oviduct
    PDK4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    PDK4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.8364

    UniProtKB/Swiss-Prot: PDK4_HUMAN, Q16654
    Tissue specificity: Ubiquitous; highest levels of expression in heart and skeletal muscle

        Pathway & Disease-focused RT2 Profiler PCR Arrays including PDK4: 
              Skeletal Muscle: Myogenesis & Myopathy in human mouse rat
              Fatty Liver in human mouse rat
              Glucose Metabolism in human mouse rat
              Cardiotoxicity in human mouse rat

    Primer
    Products:
    OriGene qPCR primer pairs and template standards for PDK4
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for PDK4 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Pdk41 , 5 pyruvate dehydrogenase kinase, isoenzyme 41, 5 86.44(n)1
    93.38(a)1
      6 (2.06 cM)5
    272731  NM_013743.21  NP_038771.11 
     54833515 
    chicken
    (Gallus gallus)
    Aves PDK41 pyruvate dehydrogenase kinase, isozyme 4 76.44(n)
    79.56(a)
      420570  NM_001199909.1  NP_001186838.1 
    lizard
    (Anolis carolinensis)
    Reptilia PDK46
    pyruvate dehydrogenase kinase, isozyme 4
    63(a)
    1 ↔ 1
    6(22566503-22580492)
    African clawed frog
    (Xenopus laevis)
    Amphibia BC059972.12   -- 77.31(n)    BC059972.1 
    zebrafish
    (Danio rerio)
    Actinopterygii pdk41 pyruvate dehydrogenase kinase, isozyme 4 68.07(n)
    72.7(a)
      561007  NM_001128704.1  NP_001122176.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Pdk3 pyruvate dehydrogenase (lipoamide)
    kinase
    53(a)     --
    worm
    (Caenorhabditis elegans)
    Secernentea ZK370.53 Phosphoprotein 50(a)   III(8809765-8813134)   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes PKP16
    Mitochondrial protein kinase involved in negative ...
    22(a)
    1 → many
    IX(275108-276292) YIL042C


    ENSEMBL Gene Tree for PDK4 (if available)
    TreeFam Gene Tree for PDK4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for PDK4 gene
    BCKDK2  PDK12  PDK22  PDK32  
    3 SIMAP similar genes for PDK4 using alignment to 3 protein entries:     PDK4_HUMAN (see all proteins):
    PDK2    PDK3    PDK1

    Find genes that share paralogs with PDK4           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for PDK4 (see all 419)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1475945491,2
    C--95212353(+) CTAATC/TTATTT 1 -- ds50010--------
    rs117638231,2
    C,F,A,H--95212415(+) GCCAGC/TAAGGT 1 -- ds50018Minor allele frequency- T:0.41NA CSA WA EA 367
    rs117638241,2
    C,F,H--95212420(+) TAAGGG/TCATTA 1 -- ds50018Minor allele frequency- T:0.41NA CSA WA EA 367
    rs757052571,2
    C,F--95212442(+) AAAGGA/CAGTTG 1 -- ds50011Minor allele frequency- C:0.03WA 118
    rs1404592331,2
    --95212447(+) AAGTTC/GTCTAT 1 -- ds50010--------
    rs284260831,2
    C,F--95212520(+) AATTTA/CACTTA 1 -- ds50013Minor allele frequency- C:0.20WA 122
    rs1809284401,2
    C--95212543(+) CTATTC/TCCACC 1 -- ds50010--------
    rs1849464481,2
    --95212565(+) CTGACA/GTTTAA 1 -- ds50010--------
    rs1909285961,2
    --95212634(+) GTATGC/TAAACA 1 -- ds50010--------
    rs1817385391,2
    --95212676(+) AATATG/TCAGAA 1 -- ds50010--------

    HapMap Linkage Disequilibrium report for PDK4 (95212809 - 95225925 bp)

    Structural Variations
          Database of Genomic Variants (DGV) variations for PDK4: --
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing PDK4
    DNA2.0 Custom Variant and Variant Library Synthesis for PDK4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 602527    OMIM disorders: --

    1 disease from the University of Copenhagen DISEASES database for PDK4:
    Systolic heart failure

    Find genes that share disorders with PDK4           About GenesLikeMe

    6 Novoseek inferred disease relationships for PDK4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    insulin resistance 43.5 2 12476789 (1), 10905486 (1)
    rhabdomyosarcoma 32.1 1 17488246 (1)
    insulin sensitivity 23.7 5 12582211 (2), 16763003 (2)
    niddm 16.2 5 15776585 (2), 9787110 (1)
    atrophy 0 1 16338907 (1)
    diabetes mellitus 0 3 12476789 (1), 15776585 (1)

    Genetic Association Database (GAD): PDK4
    Human Genome Epidemiology (HuGE) Navigator: PDK4 (3 documents)

    Export disorders for PDK4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for PDK4 gene, integrated from 10 sources (see all 123):
    (articles sorted by number of sources associating them with PDK4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity. (PubMed id 18658136)1, 2, 9 Wynn R.M.... Chuang D.T. (J. Biol. Chem. 2008)
    2. [Genetic polymorphism of pyruvate dehydrogenase kinase 4 (PDK4), paraoxonase 2 (PON2), and fatty acid binding protein 2 (FABP2) in the NIDDM population of Senegal]. (PubMed id 15776585)1, 4, 9 Che D....Trivin F. (Dakar Med 2002)
    3. Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells. (PubMed id 15955060)1, 2, 9 Abbot E.L....Yeaman S.J. (FEBS J. 2005)
    4. Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human. (PubMed id 8798399)1, 2, 9 Rowles J....Prochazka M. (J. Biol. Chem. 1996)
    5. Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta. (PubMed id 17669420)1, 2, 9 Degenhardt T....Carlberg C. (J. Mol. Biol. 2007)
    6. Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting. (PubMed id 14966024)1, 2, 9 Spriet L.L....Cameron-Smith D. (J. Appl. Physiol. 2004)
    7. Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation. (PubMed id 21852536)1, 2 Grassian A.R....Brugge J.S. (Genes Dev. 2011)
    8. Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4. (PubMed id 21904029)1, 2 Kukimoto-Niino M....Yokoyama S. (Acta Crystallogr. D 2011)
    9. Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex. (PubMed id 20715114)1, 2 Blouin J.M.... Bortoli S. (Int. J. Cancer 2011)
    10. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PubMed id 20877624)1, 4 Hendrickson S.L....O'Brien S.J. (PLoS ONE 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 5166 HGNC: 8812 AceView: PDK4 Ensembl:ENSG00000004799 euGenes: HUgn5166
    ECgene: PDK4 H-InvDB: PDK4

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for PDK4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for PDK4 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for PDK4 gene:
    Search GeneIP for patents involving PDK4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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