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FLASH GENE
Symbol PPARD contributors: mct/npt/pgu - updated : 08-06-2016
HGNC name peroxisome proliferator-activated receptor delta
HGNC id 9235
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal zinc finger C4 domain
  • C-terminal ligand binding domain
    • mono polymer heteromer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • steroid/thyroid hormone receptor family
  • NR1 subfamily
    • CATEGORY receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • gateway receptor modulating PPARA and PPARG activities
  • potent transrepressive activity
  • controlling fatty acid oxidation by regulating genes involved in fatty acid transport in skeletal muscles, thereby ameliorating obesity and insulin resistance
  • involved in the adaptive metabolic responses of skeletal muscle to environmental changes, such as long-term fasting or physical exercise, by controlling the number of oxidative myofibers
  • PPARD signaling does play an important role in the ceramide-induced stimulation of ABCA12 expression in keratinocytes
  • essential regulator of cardiac mitochondrial protection and biogenesis
  • ligand-activated PPARD exerts antiatherosclerotic effects by anti-inflammatory mechanisms
  • MMP9 expression induced by TGFA is a valid target of PPARD ligands in keratinocytes
  • regulates the stability of atherosclerotic plaques through modulation of inflammation and extracellular matrix homeostasis
  • ligand-activated PPARD regulates AGT-induced cellular senescence in VSMCs by up-regulation of PTEN and ensuing modulation of the PI3K/Akt signaling cascade
  • important regulator of fatty acid (FA) metabolism
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling hormonal
    a component
  • heterodimerizing with RXR
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with PPARGC1(inducing expression)
  • physically associating with KLF5
  • prevents the AGT-induced cellular senescence by reducing intracellular ROS generation
  • PPARD regulates the expression of PTEN at the transcriptional level
  • ANGPTL4, a multifunctional protein, is one of the major targets of PPARD in skeletal muscle cells
  • PPARD-ANGPTL4 pathway is involved in the regulation of tumor cell invasion
  • PLIN5 is a novel direct PPARD target in muscle
  • PPARD-mediated regulatory mechanism for ACSL4 expression in liver tissue and cultured hepatic cells
  • PPARD directly regulated neutral amino acid transporter SLC1A5 and SLC2A1 gene transcription, leading to uptake of glucose and amino acid, activation of MTOR signaling and tumor progression
    • cell & other
    REGULATION
    activated by AP1 (expression of PPARD is increased by AP1 activation)
    Other downregulated by APC through beta-catenin/TCF4 inactivation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • novel prognostic markers in acute myeloid leukemia with favorable outcome are PSMD2, PPARD
    • Therapy target
    SystemTypeDisorderPubmed
    diabetemetabolic syndrom 
    promising new target for the treatment of vascular diseases associated with metabolic disorders
    diabetemetabolic syndrom 
    PPARdelta agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption and decreasing obesity
    diabetetype 2 
    PPAR-delta agonists may have a potential for treating inflammatory diseases such as atherosclerosis and diabetes
    cardiovascularatheroma 
    may be a key target for therapeutic intervention in atherosclerosis by preventing cellular senescence of VSMCs
    neurologyacquired 
    pharmacological activation of PPARδ may provide a new therapeutic strategy to treat stroke-induced vascular and neuronal damage
    cardiovascular  
    PPARD activation can be a potential therapeutic target for cardiac disorders
    ANIMAL & CELL MODELS
  • targeted disruption of the mouse peroxisome proliferator-activated receptor beta results in growth, adipose, brain and skin alterations
  • endothelial-protective effect of Ppard agonists in diabetic mice through PI3K/Akt/eNOS signaling, suggesting the therapeutic potential of PPARD agonists for diabetic vasculopathy
  • long-term cardiomyocyte-restricted PPARdelta deficiency in mice leads to depressed myocardial fatty acid oxidation, bioenergetics, and premature death with lipotoxic cardiomyopathy