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FLASH GENE

Symbol

PPARG

last update : 13-01-2010

HGNC name	peroxisome proliferative activated receptor, gamma
HGNC id	9236
Corresponding disease	DIDAN insulin dependent diabetes mellitus with acanthosis nigricans FPLD3 familial partial lipodystrophy, 3, Dunnigan type PPARG marked obesity
Location	3p25.2
Synonym name	nuclear receptor subfamily 1 group C member 3
	PPAR gamma
Synonym symbol(s)	NR1C3, PPARG1, PPARG2, PPARgamma, CIMT1

DNA

RNA

EXP/sub-loc

PROTEIN

PATHOLOGY

DNA	Back to top

TYPE	functioning gene
STRUCTURE	146.51 kb     8 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	promoter with responsive element for ROR alpha (RORE) and STAT1 binding site

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	pter - D3S1263 - [D3S1259 , D3S1585 , D3S1286 , D3S1293 ] - cen
Authors	Vigouroux (98)
Text	[PPARG ]

Physical map

RNA	Back to top

TRANSCRIPTS	type	messenger

identification	nb exons	type	bp	product
				Protein	kDa	AA	specific expression	authors
NM_138712	8	-	1892	NP_619726	-	477	-	Fajas, Tontonoz, Adams (1997)
	exons A1, A2
NM_005037	7	splicing	1818	NP_005028	-	477	adipose tissues, intestine, neutrophils and peripheral blood lymphocytes£less abundant than G1	Fajas, Tontonoz, Adams (1997)
	exon B
NM_138711	8	initiation site	1919	NP_619725	-	477	-	Tontonoz, Adams (1997)
NM_015869	7	splicing	1820	NP_056953	-	505	adipocytes	Tontonoz, Zhang, Adams (1997)
	additional 30 AA at the N-terminus that render its ligand-independent activation domain ,which is more effective in activating the transcription of the PPARG reporter gene involved in the adipose tissue development and insulin sensitivity

EXPRESSION / SUBCELLULAR LOCALIZATION

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Type

expressed in	(based on citations)
organ(s)	System Organ 1 organ 2 organ 3 organ 4 level Digestive intestine large intestine

cells

System Cell   stromal cell Lymphoid/Immune macrophage

cell lineage	at high level in preadipocytes
cell lines
fluid/secretion

at STAGE

physiological period

pregnancy

Text	placenta, in the diploid trophoblast lineages for the isoform 1 and required for placental development

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

PROTEIN

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PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

DNA-binding and ligand-binding domains (LBD) linked to divergent N terminal regions, with a role for helix 7 of the LBD in regulating adipocyte function (Wang 2008)

mono polymer

heteromer , dimer

HOMOLOGY

interspecies

homolog to murine Pparg

intraspecies

Homologene

FAMILY	nuclear hormone receptor family
	NR1 subfamily

CATEGORY

receptor

basic FUNCTION	modulator of insulin sensitivity and control of glucose homeostasis and blood pressure and activation of antidiabetic effect of thiazolidinediones
	regulates transcription in response to prostanoid and thiazolidinedione ligands and promotes adipocyte differentiation (Adams 1997)
	implicated in transcriptional activation, modulated by growth factor or cytokine-stimulated signal transduction pathways involved in adipogenesis (Adams 1997)
	key regulator of adipose cell differentiation, fatty acid uptake and lipogenesis
	negative regulator of macrophage activation, inhibiting production of monocyte inflammatory cytokines and regulating both native and acquired immune responses
	jointly required for full adipocyte differentiation and fat deposition with variability influencing plasma leptin levels in obese humans
	increasing PAI1 expression in endothelial cells
	activation of PPARG inhibits osteocalcin expression both by suppressing the expression of RUNX2 and by interfering with the transactivation ability of RUNX2
	inducing acute hepatic steatosis while markedly decreasing peripheral adiposity
	key negative regulator of T helper cells secreting interleukin (IL)-17 differentiation (Klotz 2009)
	prime inducer of adipogenesis that inhibits osteoblastogenesis (Takada 2009)
	participates in the insulin-induced IDE (Insulin-degrading enzyme) expression in neurons (Du 2009)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

energetic

signaling

hormonal

a component

heterodimerizing with RXR*

INTERACTION

DNA

binding

RNA

small molecule

protein	fusion gene PAX8-PPARgamma disrupts normal transcriptional regulation by stimulating some genes and inhibiting others, and may mediate follicular thyroid cell growth and loss of differentiation that ultimately leads to carcinogenesis
	cooperation with SFRS1 for regulating UCP3 alternative splicing (alternative polyadenylation) (Kim 2009)
	functional interaction with CDX1 and CEBPA
	(CDX1 enhanced the expression of PPARG, a master transcriptional regulator of intestinal differentiation, at the transcriptional level, via functional interaction with CEBPA) (Park 2009)
	FGF21 gene is a direct target of PPARG (Wang 2008)

cell & other

REGULATION

activated by	coactivated by SRCO1
	EGR1 in vascular smooth muscle cells

induced by

CEBPB and CEBPD

inhibited by

NR0B1 in a dose-dependent manner

repressed by

STAT1 in adipocytes (transcriptional reprssion)

other

regulated through association with ligands that include the thiazolidinedione class of antidiabetic drugs, as well as derivatives of polyunsaturated fatty acids (Wang 25008)

ASSOCIATED DISORDERS

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corresponding disease(s)

PPARG , DIDAN , FPLD3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   translocation     in thyroid follicular carcinoma: t(2;3)(q13;p25), chimeric fusion protein 5' - PAX8 - PPARG - 3' tumoral     over   in colorectal carcinoma tumoral         is expressed in several MEN1-related tumor types, and loss of PPARG function may contribute to lipoma development in MEN1 patients (Dreijerink 2009) constitutional     low   leads to increased trophoblast invasion and miscarriages (Toth 2009)

Susceptibility

to hypertension to non insulin dependent diabetes to ovarian carcinoma

Variant & Polymorphism

SNP

P12A, low in renal carcinoma, and associated with decreased risk of diabetic nephropathy in type 2 diabetes H449H overexpressed in ovarian carcinomas P12A increases risk for diabetes in persons with impaired glucose tolerance, an effect modified by body mass index but having no effect on the beneficial response to troglitazone

Candidate gene
Marker
Therapy target	can protects against atherosclerosis, through stimulation of CYP27A1 represents a promising molecular target for specific immunointervention in Th17-mediated autoimmune diseases such as multiple sclerosis (Klotz 2009)
animal or cellular model