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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_177435 7 splicing 1977 NP_803184 40 361 - 2012 23023367 distinct and shorter C terminus NM_006238 8 - 3328 NP_006229 49 441 - 2012 23023367 NM_001171818 9 - 3845 NP_001165289 - 441 - 2012 23023367 NM_001171820 6 - 3455 NP_001165291 - 343 - 2012 23023367 NM_001171819 7 - 3518 NP_001165290 - 402 - 2012 23023367

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune spleen       highly Reproductive female system ovary     highly   female system placenta     highly Respiratory respiratory tract larynx     highly Skin/Tegument skin         Urinary bladder       highly

cells

System Cell Pubmed Species Stage Rna symbol Skin/Tegument keratinocyte

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
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed diabete metabolic syndrom   promising new target for the treatment of vascular diseases associated with metabolic disorders diabete metabolic syndrom   PPARdelta agonists may have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption and decreasing obesity diabete type 2   PPAR-delta agonists may have a potential for treating inflammatory diseases such as atherosclerosis and diabetes cardiovascular atheroma   may be a key target for therapeutic intervention in atherosclerosis by preventing cellular senescence of VSMCs neurology acquired   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