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FLASH GENE
Symbol PPARA contributors: mct - updated : 22-06-2017
HGNC name peroxisome proliferative activated receptor, alpha
HGNC id 9232
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a zinc-finger domain, C4 type
  • one nuclear receptor DNA-binding domain
    • mono polymer heteromer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • steroid/thyroid hormone receptor superfamily
  • nuclear hormone receptor family
  • NR1 subfamily
    • CATEGORY regulatory , transcription factor , receptor nuclear
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • involved in the control of fatty acid synthesis, oxidation and ketogenesis
  • playing a critical role in the cellular fasting response
  • involved in the metabolic control of the expression of the genes encoding fatty acid oxidation enzymes
  • controlling the intracellular CoA concentration via regulation of PANK1alpha expression
  • regulates lipid homeostasis, particularly in the liver
  • role for PPARA in fasting-mediated oxidative stress
  • its activation upregulates nephrin expression in embryonic kidney epithelial cells and podocytes by a dual mechanism
  • important regulator of hepatic lipid metabolism and the acute phase response
  • may still play a role in the regulation of the bifurcation of the adipomyocyte precursor into a brown adipocyte or myocyte phenotype
  • key regulator for maintaining whole-body energy balance
  • its activation stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes
  • is a novel regulatory factor in SREBF1 regulation which plays a relevant role in the interplay between lipids and insulin metabolic regulation
  • could play a role as a nutritional status sensor in the cell to regulate the SREBF1-dependent pathway by controlling the fasting/fed transition
  • NR1H3 (liver X receptor) and PPARA are nuclear receptors that control the expression of genes involved in glucose and lipid homoeostasis
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    peroxisomal fatty acid pathway
    a component
  • heterodimerizing with RXR
  • SIK2-EP300-PPARA cascade mediates glucagon effect on ketogenesis
    • INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • NCOA3 and NCOA6 coactivators
  • binds to a direct repeat of two hexanucleotides spaced by one nucleotide, as heterodimers with the retinoid X receptor (NR1H3)
  • hepatic ALAS1 is a new direct target for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARA)
  • interacting with CYP2J2 (activates the nuclear receptor PPARA)
  • requires transcription coactivator PPAR-binding protein (PBP)/mediator subunit 1(MED1) for its transcriptional activity
  • major involvement of the SIRT1-PPARA interaction in the protective role of SIRT1 against cardiac hypertrophy
  • fatty acids act as ligands for PPARA, and the activated PPARA receptor then stimulates the transcription of genes encoding proteins involved in the uptake and/or metabolism of lipids, cholesterol, and glucose metabolism
  • FNDC5 acts to induce UCP1 gene expression, at least in part, via PPARA
  • DDIT3 is necessary for suppression of genes encoding the transcriptional master regulators of lipid metabolism: CEBPA, PPARA, and SREBF1
  • feedback loop between MXIPL and PPARA plays an important role in the regulation of lipogenesis in brown adipocytes
  • MECR is a binding protein of the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARA), but the presence of a cytosolic or nuclear isoform of MECR is necessary for functional interaction between MECR and PPARA
  • PPARA controls IGF1 signalling through the up-regulation of hepatic IGFBP2 transcription during fasting
  • specific drug-FABP1, FABP2 complexes can interact with PPARA to effect nuclear accumulation of FABP1, FABP2 and Nuclear hormone receptors (NHRs) activation
  • EP300 interacts with PPARA through a conserved LXXLL motif and enhances its transcriptional activity
  • ANGPTL6-mediated increase in PPARA expression resulted in increased FGF21 expression, thereby promoting beta-oxidation
  • PPARA is a transcription factor that transactivates SLC47A1
    • cell & other
    REGULATION
    activated by fatty acids
    inhibitors of mitochondrial long-chain fatty acid import
    drugs to treat human disorders of lipid metabolism
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to familial combined hyperlipidemia (gene modifier)
  • to atherosclerosis or coronary heart disease
    • Variant & Polymorphism other L162V might protect against the development of atherosclerosis or coronary heart disease in patients with type 2 diabetes (protective effects are exerted directly on the arterial wall)
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS