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FLASH GENE
Symbol PDK1 contributors: mct/npt - updated : 06-02-2015
HGNC name pyruvate dehydrogenase kinase, isozyme 1
HGNC id 8809
DNA
TYPE functioning gene
STRUCTURE 43.08 kb     11 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Physical map
LOC285140 2q31.1 eukaryotic translation initiation factor 2 beta-like pseudogene LOC389059 2 LOC389059 LOC285141 2q31.1 similar to CG14853-PB GAD1 2q31 glutamate decarboxylase 1 (brain, 67kDa) GORASP2 2p24.3-q21.3 golgi reassembly stacking protein 2, 55kDa TLK1 8p22-p12 tousled-like kinase 1 FLJ13984 2q31.1 hypothetical protein FLJ13984 FLJ13096 2q31.1 hypothetical protein FLJ13096 MRPS29P2 2q31.2 mitochondrial ribosomal protein S29 pseudogene 2 LOC389060 2 similar to ribosomal protein S15 CYBRD1 2q31 cytochrome b reductase 1 LOC391460 2 similar to 60S ribosomal protein L21 DNCI2 2q24-q31 dynein, cytoplasmic, intermediate polypeptide 2 SLC25A12 2q24-q31 solute carrier family 25 (mitochondrial carrier, Aralar), member 12 HAT1 2q31.2-q33.1 histone acetyltransferase 1 MAP1D 2q31.1 methionine aminopeptidase 1D DLX1 2q32 distal-less homeo box 1 DLX2 2q32 distal-less homeo box 2 ITGA6 2q22-q31 integrin, alpha 6 PDK1 2q31.1 pyruvate dehydrogenase kinase, isoenzyme 1 CGEF2 2q31 pyruvate dehydrogenase kinase, isoenzyme 1 ZAK 2q24.2 pyruvate dehydrogenase kinase, isoenzyme 1 LOC391461 2 similar to ribosomal protein S2; 40S ribosomal protein S2 CDCA7 2q31 cell division cycle associated 7 LOC344178 2q31.1 similar to peptidylprolyl isomerase A (cyclophilin A) LOC344181 2q31.1 similar to ribosomal protein L5; 60S ribosomal protein L5 SP3 2q31 Sp3 transcription factor LOC389061 2 LOC389061 LOC389062 2 LOC389062 LOC391462 2 similar to protein 40kD PTD004 2q31.1 hypothetical protein PTD004 LOC391463 2 similar to Leucine-rich repeat-containing protein 2 LOC389063 2 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP-1) (Topoisomerase-inhibitor suppressed)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 - 4576 - 436 - 1995 7499431
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   predominantly
Digestivemouth   highly
Endocrineadrenal gland   highly
Visualeye   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one histidine kinase domain
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to murine Pdk1
    ortholog to rattus Pdk1
    Homologene
    FAMILY
  • PDK/BCKDK protein kinase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    basic FUNCTION
  • phosphorylating PDH and resulting in its inactivation and thus contributing to the regulation of glucose metabolism
  • plays an important role in maintaining glycolysis
  • activates a group of kinases, including AKT1, p70 ribosomal S6 kinase (S6K), and serum and glucocorticoid-induced protein kinase (SGK), that mediate many of the effects of insulin as well as other agonists
  • BNIP3 and PDK1 are involved in two important pathways, cell death and glycolytic, playing critical roles in these pathways in cardiomyocytes after severe hypoxia
  • plays an indispensable role in the development of the cardiovascular system
  • important regulator of PDH in clonal beta-cells and PDK1 and PDH are important for efficient metabolic coupling
  • PDK1 and PDK2 promote meiotic maturation, as their knockdown disturbs the assembly of the meiotic apparatus, without significantly altering ATP content
  • CELLULAR PROCESS protein, post translation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    glucose metabolism
    a component
  • heterodimerizing with PDK2
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP binding
  • protein
  • binding STRAP
  • interacts with phosphoinositides through a pleckstrin homology (PH) domain
  • PDK1 positively modulates CDC42BPA activity and drives its localization within lamellipodia
  • cell & other
    REGULATION
    Other regulated by HIF1A (HIF regulation has a key role in maintaining lactate production in human cancer)
    regulation by HIF1A (HIF-1-mediated expression of PDK1: a metabolic switch required for cellular adaptation to hypoxia)
    tyrosine phosphorylation enhances PDK1 kinase activity by promoting ATP and pyruvate dehydrogenase complex binding
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    associated with poor prognosis in head and neck squamous cancer
    constitutional     --low  
    in patients with Alzheimer disease compared with nondemented patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    PDK1 inhibition could serve as a novel therapeutic approach, in multiple myeloma
    cancer  
    PDK1 inhibitors should be investigated for antitumour effects
    ANIMAL & CELL MODELS