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FLASH GENE
Symbol PPARD contributors: mct/npt/pgu - updated : 08-06-2014
HGNC name peroxisome proliferator-activated receptor delta
HGNC id 9235
Location 6p21.31      Physical location : 35.310.334 - 35.395.966
Synonym name
  • peroxisome proliferative activated receptor, delta
  • nuclear hormone receptor 1
  • nuclear receptor subfamily 1 group C member 2
  • Synonym symbol(s) NUC1, PPARB, NR1C2, FAAR, MGC3931, NUCI, NUCII
    DNA
    TYPE functioning gene
    STRUCTURE 85.63 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC391914 6 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) CYCSL1 6p21.31 cytochrome c, somatic-like 1 HMGA1 6p21.3 high mobility group AT-hook 1 MGC57858 6p21.31 hypothetical protein MGC57858 LOC391915 6 hypothetical gene supported by U12465; NM_007209 NUDT3 6p21.2 nudix (nucleoside diphosphate linked moiety X)-type motif 3 RPS10 6p21.3 ribosomal protein S10 PACSIN1 6p21.3 protein kinase C and casein kinase substrate in neurons 1 SPDEF 6p21.3 SAM pointed domain containing ets transcription factor C6orf106 6p21.31 chromosome 6 open reading frame 106 MGC4614 6p21.31 hypothetical protein MGC4614 LOC391916 6 hypothetical gene supported by BC001032; NM_001014 SNRPC 6p21.2 small nuclear ribonucleoprotein polypeptide C C6orf107 6p21 chromosome 6 open reading frame 107 TAF11 6p21 TAF11 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 28kDa ANKS1 6p21.31 ankyrin repeat and SAM domain containing 1 TCP11 6p21.2 t-complex 11 (mouse) CEGF3 6p21.3 CUB domain and EGF-like repeat containing 3 ZNF76 6p21.2 zinc finger protein 76 (expressed in testis) DEF6 6p21.33-p21.1 differentially expressed in FDCP 6 homolog (mouse) PPARD 6p21.2-p21.1 peroxisome proliferative activated receptor, delta MKRNP2 6p21.1 makorin, ring finger protein, pseudogene 2 FANCE 6p22-p21 Fanconi anemia, complementation group E RPL10A 6p21.3 ribosomal protein L10a TEAD3 6p21.2 TEA domain family member 3 TULP1 6p21.3 tubby like protein 1 LOC389382 6 similar to Rps15a protein FKBP5 6p21.3-p21.2 FK506 binding protein 5 C6orf81 6p21.31 chromosome 6 open reading frame 81 LOC389383 6 similar to AAAL3045 LOC340204 6p21.31 similar to precursor peptide CLPS 6p22-p21.1 colipase, pancreatic MGC33835 6p21.31 hypothetical protein MGC33835 SRPK1 6p213-p21.2 SFRS protein kinase 1 SLC26A8 6p21 solute carrier family 26, member 8 MAPK14 6p21.2 mitogen-activated protein kinase 14 MAPK13 6p21.1 mitogen-activated protein kinase 13 BRPF3 6p21 bromodomain and PHD finger containing, 3 PNPLA1 6p21.31 patatin-like phospholipase domain containing 1 LOC389384 6 similar to RIKEN cDNA 4930539E08 ETV7 6p21 ets variant gene 7 (TEL2 oncogene )
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 splicing 1977 40 361 - 2012 23023367
    distinct and shorter C terminus
    8 - 3328 49 441 - 2012 23023367
    9 - 3845 - 441 - 2012 23023367
    6 - 3455 - 343 - 2012 23023367
    7 - 3518 - 402 - 2012 23023367
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   highly
    Reproductivefemale systemovary  highly
     female systemplacenta  highly
    Respiratoryrespiratory tractlarynx  highly
    Skin/Tegumentskin    
    Urinarybladder   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentkeratinocyte
    cell lineage preadipocytes
    cell lines
    fluid/secretion
    at STAGE
    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
  • 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