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FLASH GENE
Symbol PPARA contributors: mct - updated : 22-06-2015
HGNC name peroxisome proliferative activated receptor, alpha
HGNC id 9232
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestiveliver   highly
Endocrineadrenal gland   highly
Reproductivemale systemprostate   
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal highly
cells
SystemCellPubmedSpeciesStageRna symbol
Digestivehepatocyte
Lymphoid/ImmuneB cell
cell lineage
cell lines
fluid/secretion
at STAGE
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
  • 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