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FLASH GENE
Symbol PPARA contributors: mct - updated : 22-06-2015
HGNC name peroxisome proliferative activated receptor, alpha
HGNC id 9232
Location 22q13.31      Physical location : 46.546.498 - 46.639.653
Synonym symbol(s) H9232, NR1C1, hPPAR
DNA
TYPE functioning gene
STRUCTURE 93.15 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter (TATA box)
cytosine-phosphate-guanine/HTF
Binding site   HRE
text structure
  • a regulatory element (RE) consisting of a degenerate hexamer repeat with a single nucleotide spacer (direct repeat 1), termed alphaHNF4-RE, leading to an induction of PPARalpha expression in hepatocytes
  • three new novel exons at the 5(') - untranslated region were also identified and designated as Exon A, Exon B, and Exon 2b
  • with RXRA bind to the PPRE in the PDZK1 promoter
  • MAPPING cloned Y linked Y status confirmed
    Physical map
    HMG17L1 22q13.31 high-mobility group (nonhistone chromosomal) protein 17-like 1 SULT4A1 22q13.2-q13.31 sulfotransferase family 4A, member 1 LOC150379 22q13.31 GS2 like C22orf20 22q13.31 chromosome 22 open reading frame 20 CGI-51 22q13.31 CGI-51 protein PARVB 22q13.2-q13.33 parvin, beta TRSPP1 22q11 tRNA phosphoserine (opal suppressor) pseudogene 1 PARVG 22q13.2-q13 parvin, gamma LOC388909 22 LOC388909 MRPS18CP6 22q13.31 mitochondrial ribosomal protein S18C pseudogene 6 DKFZp761O17121 22q13.31 hypothetical protein DKFZp761O17121 LOC129186 22q13.31 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC388910 22 LOC388910 ARHGAP8 22q13.31 Rho GTPase activating protein 8 LOC112885 22q13.31 hypothetical protein BC012187 NUP50 22q13.31 nucleoporin 50kDa KIAA0930 22q13.31 nucleoporin 50kDa UPK3A 22q13.31 uroplakin 3A FLJ20635 22q13 hypothetical protein FLJ20635 SMC1L2 22q13.31 SMC1 structural maintenance of chromosomes 1-like 2 (yeast) DKFZP566F0546 22q13.31 DKFZP566F0546 protein FBLN1 22q13.31 fibulin 1 LOC388911 22 LOC388911 E46L 22q13.31 LOC388911 LOC388912 22 LOC388912 FLJ10945 22q13.31 hypothetical protein FLJ10945 LOC388913 22 similar to seroreactive antigen BMN1-2 LOC150381 22q13.31 hypothetical protein LOC150381 PPARA 22q13.3 peroxisome proliferative activated receptor, alpha MGC2452 22q13.31 hypothetical protein MGC2452 LOC150383 22q13.31 similar to RIKEN cDNA 2210021J22 PKDREJ 22q13.32 polycystic kidney disease (polycystin) and REJ (sperm receptor for egg jelly homolog, sea urchin)-like FLJ20699 22q13 hypothetical protein FLJ20699 GTSE1 22q13.2-q13.3 G-2 and S-phase expressed 1 FLJ10140 22q13 hypothetical protein FLJ10140 CELSR1 22q13.32 cadherin, EGF LAG seven-pass G-type receptor 1 (flamingo homolog, Drosophila) KIAA0767 22q13.31 cadherin, EGF LAG seven-pass G-type receptor 1 (flamingo homolog, Drosophila) CERK 22q13.31 ceramide kinase C22orf4 22q13.3 chromosome 22 open reading frame 4 LOC391338 22 similar to 60S ribosomal protein L10 (QM protein homolog) LOC388914 22 LOC388914 LOC284931 22q13.32 hypothetical LOC284931 LOC388915 22 LOC388915
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 9965 52.2 468 - 2001 21443859
  • PPARA I1 V3
  • - - 8208 52.2 468 - 2001 21443859
    - - 8497 52.2 468 - 2001 21443859
    9 - 10049 52.2 468 - 2001 21443859
  • PPARA I1 V5
  • - - 1571 28.2 258 - 2001 21443859
    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