Reviewed, UniProtKB/Swiss-Prot P37231 (PPARG_HUMAN)

Names and origin

Protein names

Recommended name:
    Peroxisome proliferator-activated receptor gamma
      Short name=PPAR-gamma
Alternative name(s):
    Nuclear receptor subfamily 1 group C member 3

Gene names

Name:	PPARG
Synonyms:	NR1C3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	505 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Ref.1
Subunit structure	Forms a heterodimer with the retinoic acid receptor RXRA called adipocyte-specific transcription factor ARF6. Interacts with NCOA6 coactivator, leading to a strong increase in transcription of target genes. Interacts with coactivator PPARBP, leading to a mild increase in transcription of target genes. Interacts with FAM120B By similarity. Interacts with NOCA7 in a ligand-inducible manner. Interacts with NCOA1 LXXLL motifs. Interacts with TGFB1I1. Interacts with DNTTIP2.
Subcellular location	Nucleus.
Tissue specificity	Highest expression in adipose tissue. Lower in skeletal muscle, spleen, heart and liver. Also detectable in placenta, lung and ovary. Ref.1
Polymorphism	Genetic variation in PPARG may influence body mass index (BMI) [MIM:606641]. BMI reflects the amount of fat, lean mass, and body build.
Involvement in disease	Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. Defects in PPARG may be associated with susceptibility to obesity [MIM:601665]. Defects in PPARG may be associated with colon cancer. Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM:604367]. Familial partial lipodystrophies (FPLD) are a heterogeneous group of genetic disorders characterized by marked loss of subcutaneous (sc) fat from the extremities. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia. Ref.39 Ref.40 Variation in PPARG is associated with carotid intimal medial thickness 1 (CIMT1) [MIM:609338]. CIMT is a measure of atherosclerosis that is independently associated with traditional atherosclerotic cardiovascular disease risk factors and coronary atherosclerotic burden. 35 to 45% of the variability in multivariable-adjusted CIMT is explained by genetic factors.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.
Sequence caution	The sequence BAA23354.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus Disease mutation Obesity
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Receptor
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell fate commitment Inferred from sequence or structural similarity. Source: UniProtKB cell maturation Inferred from direct assay. Source: UniProtKB cellular response to insulin stimulus Ref.38 Inferred from mutant phenotype. Source: UniProtKB epithelial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB glucose homeostasis Ref.38 Inferred from mutant phenotype. Source: UniProtKB innate immune response Traceable author statement. Source: UniProtKB lipid homeostasis Traceable author statement. Source: UniProtKB lipid metabolic process Traceable author statement. Source: ProtInc lipoprotein transport Inferred from direct assay. Source: UniProtKB long-chain fatty acid transport Inferred from sequence or structural similarity. Source: UniProtKB low-density lipoprotein receptor biosynthetic process Inferred from direct assay. Source: UniProtKB monocyte differentiation Inferred from direct assay. Source: UniProtKB negative regulation of cholesterol storage Inferred from direct assay. Source: UniProtKB negative regulation of foam cell differentiation Inferred from direct assay. Source: UniProtKB negative regulation of receptor biosynthetic process Inferred from direct assay. Source: UniProtKB negative regulation of sequestering of triglyceride Inferred from direct assay. Source: UniProtKB negative regulation of specific transcription from RNA polymerase II promoter Inferred from direct assay. Source: UniProtKB placenta development Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of fat cell differentiation Inferred from sequence or structural similarity. Source: HGNC positive regulation of specific transcription from RNA polymerase II promoter Inferred from direct assay. Source: UniProtKB regulation of blood pressure Ref.38 Inferred from mutant phenotype. Source: UniProtKB response to lipid Inferred from sequence or structural similarity. Source: UniProtKB response to low density lipoprotein stimulus Inferred from direct assay. Source: UniProtKB response to nutrient Traceable author statement. Source: ProtInc signal transduction Inferred from direct assay. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW white fat cell differentiation Traceable author statement. Source: UniProtKB
Cellular component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	arachidonic acid binding Inferred from sequence or structural similarity. Source: UniProtKB drug binding Ref.38 Inferred from direct assay. Source: UniProtKB prostaglandin receptor activity Traceable author statement. Source: UniProtKB protein heterodimerization activity Ref.20 Traceable author statement. Source: UniProtKB retinoid X receptor binding Inferred from direct assay. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription activator activity Inferred from sequence or structural similarity. Source: UniProtKB transcription activator binding Ref.38 Inferred from direct assay. Source: UniProtKB transcription factor activity Inferred from direct assay. Source: UniProtKB transcription repressor activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EDF1	O60869	4	EBI-781384,EBI-781301
EP300	Q09472	1	EBI-781384,EBI-447295
MED1	Q15648	1	EBI-781384,EBI-394459
SMARCA4	P51532	1	EBI-781384,EBI-302489
SMARCD3	Q6STE5-1	2	EBI-781384,EBI-488506
SMARCD3	Q6STE5-2	2	EBI-781384,EBI-488511

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 2 (identifier: P37231-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: P37231-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 505

505

Peroxisome proliferator-activated receptor gamma

PRO_0000053492

Regions

DNA binding

136 – 210

75

Nuclear receptor

Zinc finger

139 – 159

21

NR C4-type

Zinc finger

176 – 198

23

NR C4-type

Region

205 – 280

76

Interaction with FAM120B By similarity

Region

317 – 505

189

Ligand-binding

Sites

Binding site

317

1

Synthetic agonist

Binding site

351

1

Synthetic agonist

Binding site

477

1

Synthetic agonist

Binding site

501

1

Synthetic agonist

Amino acid modifications

Modified residue

112

1

Phosphoserine; by MAPK By similarity

Natural variations

Alternative sequence

1 – 28

28

Missing in isoform 1.

VSP_003645

Natural variant

12

1

P → A Significant independent determinant of CIMT; may protect from early atherosclerosis in subject at risk for diabetes; associated with BMI. dbSNP rs1801282. Ref.11 Ref.32 Ref.34 Ref.35 Ref.36 Ref.37 Ref.41 Ref.42 Ref.43

VAR_010723

Natural variant

40

1

P → A: dbSNP rs1805192. Ref.34 Ref.36 Ref.41 Ref.42

VAR_016116

Natural variant

113

1

P → Q in obesity. dbSNP rs1800571. Ref.33

VAR_010724

Natural variant

314

1

Q → P in colon cancer; sporadic; somatic mutation; loss of ligand-binding. dbSNP rs28936407. Ref.37

VAR_010725

Natural variant

316

1

R → H in colon cancer; sporadic; somatic mutation; partial loss of ligand-binding. dbSNP rs28936407. Ref.37

VAR_010726

Natural variant

318

1

V → M in diabetes. Ref.38

VAR_010727

Natural variant

388

1

F → L in FPLD3. Ref.39

VAR_022700

Natural variant

425

1

R → C in FPLD3. Ref.40

VAR_022701

Natural variant

495

1

P → L in diabetes. Ref.38

VAR_010728

Experimental info

Sequence conflict

36 – 37

2

MP → IA in BAA18949. Ref.3

Sequence conflict

213 – 214

2

MP → IA in BAA18949. Ref.3

Sequence conflict

240

1

R → RQ in BAA18949. Ref.3

Secondary structure

1

.

.

.

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505

Helix Strand Turn

Details...

Helix

236 – 253

18

Helix

258 – 266

9

Beta strand

275 – 277

3

Helix

280 – 287

8

Helix

289 – 292

4

Beta strand

301 – 303

3

Helix

305 – 329

25

Helix

339 – 358

20

Helix

359 – 361

3

Beta strand

364 – 369

6

Turn

370 – 373

4

Beta strand

374 – 377

4

Helix

378 – 383

6

Helix

388 – 390

3

Helix

393 – 403

11

Helix

409 – 420

12

Helix

431 – 452

22

Helix

459 – 487

29

Helix

495 – 501

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified April 27, 2001. Version 3. Checksum: 3933EFF36A0E4CAF	FASTA	505	57,620
	10 20 30 40 50 60 MGETLGDSPI DPESDSFTDT LSANISQEMT MVDTEMPFWP TNFGISSVDL SVMEDHSHSF 70 80 90 100 110 120 DIKPFTTVDF SSISTPHYED IPFTRTDPVV ADYKYDLKLQ EYQSAIKVEP ASPPYYSEKT 130 140 150 160 170 180 QLYNKPHEEP SNSLMAIECR VCGDKASGFH YGVHACEGCK GFFRRTIRLK LIYDRCDLNC 190 200 210 220 230 240 RIHKKSRNKC QYCRFQKCLA VGMSHNAIRF GRMPQAEKEK LLAEISSDID QLNPESADLR 250 260 270 280 290 300 ALAKHLYDSY IKSFPLTKAK ARAILTGKTT DKSPFVIYDM NSLMMGEDKI KFKHITPLQE 310 320 330 340 350 360 QSKEVAIRIF QGCQFRSVEA VQEITEYAKS IPGFVNLDLN DQVTLLKYGV HEIIYTMLAS 370 380 390 400 410 420 LMNKDGVLIS EGQGFMTREF LKSLRKPFGD FMEPKFEFAV KFNALELDDS DLAIFIAVII 430 440 450 460 470 480 LSGDRPGLLN VKPIEDIQDN LLQALELQLK LNHPESSQLF AKLLQKMTDL RQIVTEHVQL 490 500 LQVIKKTETD MSLHPLLQEI YKDLY
	Isoform 1. Checksum: 1061C2074B739E0A	FASTA	477	54,681
	10 20 30 40 50 60 MTMVDTEMPF WPTNFGISSV DLSVMEDHSH SFDIKPFTTV DFSSISTPHY EDIPFTRTDP 70 80 90 100 110 120 VVADYKYDLK LQEYQSAIKV EPASPPYYSE KTQLYNKPHE EPSNSLMAIE CRVCGDKASG 130 140 150 160 170 180 FHYGVHACEG CKGFFRRTIR LKLIYDRCDL NCRIHKKSRN KCQYCRFQKC LAVGMSHNAI 190 200 210 220 230 240 RFGRMPQAEK EKLLAEISSD IDQLNPESAD LRALAKHLYD SYIKSFPLTK AKARAILTGK 250 260 270 280 290 300 TTDKSPFVIY DMNSLMMGED KIKFKHITPL QEQSKEVAIR IFQGCQFRSV EAVQEITEYA 310 320 330 340 350 360 KSIPGFVNLD LNDQVTLLKY GVHEIIYTML ASLMNKDGVL ISEGQGFMTR EFLKSLRKPF 370 380 390 400 410 420 GDFMEPKFEF AVKFNALELD DSDLAIFIAV IILSGDRPGL LNVKPIEDIQ DNLLQALELQ 430 440 450 460 470 LKLNHPESSQ LFAKLLQKMT DLRQIVTEHV QLLQVIKKTE TDMSLHPLLQ EIYKDLY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgamma1 and activation with retinoid X receptor agonists and antagonists." Mukherjee R., Jow L., Croston G.E., Paterniti J.R. Jr. J. Biol. Chem. 272:8071-8076(1997) [PubMed: 9065481] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY. Tissue: Heart.
[2]	"Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2." Elbrecht A., Chen Y., Cullinan C.A., Hayes N., Leibowitz M.D., Moller D.E., Berger J. Biochem. Biophys. Res. Commun. 224:431-437(1996) [PubMed: 8702406] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Adipose tissue.
[3]	"Differential expression of PPAR gamma1 and gamma2 isoforms in human adipose tissue." Yanase T., Yashiro T., Takitani K., Kato S., Taniguchi S., Takayanagi R., Nawata H. Biochem. Biophys. Res. Commun. 233:320-324(1997) [PubMed: 9144532] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Adipose tissue.
[4]	"Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping." Greene M.E., Blumberg B., McBride O.W., Yi H.F., Kronquist K., Kwan K., Hsieh L., Greene G., Nimer S.D. Gene Expr. 4:281-299(1995) [PubMed: 7787419] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Bone marrow.
[5]	Greene M.E. Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 36; 37; 213; 214 AND 240.
[6]	"No coding mutations are detected in the peroxisome proliferator-activated receptor-gamma gene in Japanese patients with lipoatrophic diabetes." Okazawa H., Mori H., Tamori Y., Araki S., Niki T., Masugi J., Kawanishi M., Kubota T., Shinoda H., Kasuga M. Diabetes 46:1904-1906(1997) [PubMed: 9356045] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). Tissue: Placenta.
[7]	"A human peroxisome-proliferator-activated receptor-gamma is activated by inducers of adipogenesis, including thiazolidinedione drugs." Lambe K.G., Tugwood J.D. Eur. J. Biochem. 239:1-7(1996) [PubMed: 8706692] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[8]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[9]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[10]	"Human Protein Factory: an infrastructure to convert the human transcriptome into the in vitro-expressed human proteome of versatile utility." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[11]	SeattleSNPs variation discovery resource Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-12.
[12]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[14]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[15]	"Cloning and characterization of RAP250, a nuclear receptor coactivator." Caira F., Antonson P., Pelto-Huikko M., Treuter E., Gustafsson J.-A. J. Biol. Chem. 275:5308-5317(2000) [PubMed: 10681503] [Abstract] Cited for: INTERACTION WITH NCOA6.
[16]	"ERAP140, a conserved tissue-specific nuclear receptor coactivator." Shao W., Halachmi S., Brown M. Mol. Cell. Biol. 22:3358-3372(2002) [PubMed: 11971969] [Abstract] Cited for: INTERACTION WITH NOCA7.
[17]	"ERBP, a novel estrogen receptor binding protein enhancing the activity of estrogen receptor." Bu H., Kashireddy P., Chang J., Zhu Y.T., Zhang Z., Zheng W., Rao S.M., Zhu Y.-J. Biochem. Biophys. Res. Commun. 317:54-59(2004) [PubMed: 15047147] [Abstract] Cited for: INTERACTION WITH DNTTIP2.
[18]	"Hic-5 regulates an epithelial program mediated by PPARgamma." Drori S., Girnun G.D., Tou L., Szwaya J.D., Mueller E., Xia K., Shivdasani R.A., Spiegelman B.M. Genes Dev. 19:362-375(2005) [PubMed: 15687259] [Abstract] Cited for: INTERACTION WITH TGFB1I1.
[19]	"Crystal structure of the ligand binding domain of the human nuclear receptor PPARgamma." Uppenberg J., Svensson C., Jaki M., Bertilsson G., Jendeberg L., Berkenstam A. J. Biol. Chem. 273:31108-31112(1998) [PubMed: 9813012] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 232-505.
[20]	"Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma." Nolte R.T., Wisely G.B., Westin S., Cobb J.E., Lambert M.H., Kurokawa R., Rosenfeld M.G., Willson T.M., Glass C.K., Milburn M.V. Nature 395:137-143(1998) [PubMed: 9744270] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 235-504 IN COMPLEXES WITH THE SYNTHETIC AGONIST ROSIGLITAZONE AND NCOA1, SUBUNIT.
[21]	"Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors." Gampe R.T. Jr., Montana V.G., Lambert M.H., Miller A.B., Bledsoe R.K., Milburn M.V., Kliewer S.A., Willson T.M., Xu H.E. Mol. Cell 5:545-555(2000) [PubMed: 10882139] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEXES WITH RXRA AND SYNTHETIC AGONISTS.
[22]	"Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors." Xu H.E., Lambert M.H., Montana V.G., Plunket K.D., Moore L.B., Collins J.L., Oplinger J.A., Kliewer S.A., Gampe R.T. Jr., McKee D.D., Moore J.T., Willson T.M. Proc. Natl. Acad. Sci. U.S.A. 98:13919-13924(2001) [PubMed: 11698662] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 234-505 IN COMPLEXES WITH SYNTHETIC AGONIST AND NCOA1.
[23]	"Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ 242; ligand selectivity and agonist activation in the PPAR family." Cronet P., Petersen J.F.W., Folmer R., Blomberg N., Sjoeblom K., Karlsson U., Lindstedt E.-L., Bamberg K. Structure 9:699-706(2001) [PubMed: 11587644] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 225-505 IN COMPLEX WITH SYNTHETIC AGONIST.
[24]	"Synthesis and biological and structural characterization of the dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist ragaglitazar." Ebdrup S., Pettersson I., Rasmussen H.B., Deussen H.-J., Frost Jensen A., Mortensen S.B., Fleckner J., Pridal L., Nygaard L., Sauerberg P. J. Med. Chem. 46:1306-1317(2003) [PubMed: 12672231] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 230-505 IN COMPLEX WITH SYNTHETIC AGONIST.
[25]	"A new class of peroxisome proliferator-activated receptor agonists with a novel binding epitope shows antidiabetic effects." Oestberg T., Svensson S., Selen G., Uppenberg J., Thor M., Sundbom M., Sydow-Baeckman M., Gustavsson A.-L., Jendeberg L. J. Biol. Chem. 279:41124-41130(2004) [PubMed: 15258145] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 232-505 IN COMPLEX WITH NCOA2 AND SYNTHETIC AGONIST.
[26]	"Structure-based design of potent retinoid X receptor alpha agonists." Haffner C.D., Lenhard J.M., Miller A.B., McDougald D.L., Dwornik K., Ittoop O.R., Gampe R.T. Jr., Xu H.E., Blanchard S., Montana V.G., Consler T.G., Bledsoe R.K., Ayscue A., Croom D. J. Med. Chem. 47:2010-2029(2004) [PubMed: 15056000] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 235-505 IN COMPLEX WITH RXRA; NCOA1 AND SYNTHETIC AGONIST.
[27]	"Design and synthesis of alpha-aryloxyphenylacetic acid derivatives: a novel class of PPARalpha/gamma dual agonists with potent antihyperglycemic and lipid modulating activity." Shi G.Q., Dropinski J.F., McKeever B.M., Xu S., Becker J.W., Berger J.P., MacNaul K.L., Elbrecht A., Zhou G., Doebber T.W., Wang P., Chao Y.-S., Forrest M., Heck J.V., Moller D.E., Jones A.B. J. Med. Chem. 48:4457-4468(2005) [PubMed: 15974597] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 231-505 IN COMPLEX WITH SYNTHETIC AGONIST.
[28]	"Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner." Li Y., Choi M., Suino K., Kovach A., Daugherty J., Kliewer S.A., Xu H.E. Proc. Natl. Acad. Sci. U.S.A. 102:9505-9510(2005) [PubMed: 15976031] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 234-505 IN COMPLEX WITH SYNTHETIC AGONIST AND NR0B2.
[29]	"Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-gamma binding agents with potential application to the treatment of osteoporosis." Hopkins C.R., O'neil S.V., Laufersweiler M.C., Wang Y., Pokross M., Mekel M., Evdokimov A., Walter R., Kontoyianni M., Petrey M.E., Sabatakos G., Roesgen J.T., Richardson E., Demuth T.P. Jr. Bioorg. Med. Chem. Lett. 16:5659-5663(2006) [PubMed: 16919947] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 234-505 IN COMPLEX WITH SYNTHETIC AGONIST AND NCOA1.
[30]	"Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists: design, synthesis, structural biology, and molecular docking studies." Mahindroo N., Wang C.-C., Liao C.-C., Huang C.-F., Lu I.-L., Lien T.-W., Peng Y.-H., Huang W.-J., Lin Y.-T., Hsu M.-C., Lin C.-H., Tsai C.-H., Hsu J.-T., Chen X., Lyu P.-C., Chao Y.-S., Wu S.-Y., Hsieh H.-P. J. Med. Chem. 49:1212-1216(2006) [PubMed: 16451087] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 235-505 IN COMPLEX WITH SYNTHETIC AGONIST.
[31]	"Structure-based drug design of a novel family of PPARgamma partial agonists: virtual screening, X-ray crystallography, and in vitro/in vivo biological activities." Lu I.-L., Huang C.-F., Peng Y.-H., Lin Y.-T., Hsieh H.-P., Chen C.-T., Lien T.-W., Lee H.-J., Mahindroo N., Prakash E., Yueh A., Chen H.-Y., Goparaju C.M.V., Chen X., Liao C.-C., Chao Y.-S., Hsu J.-T., Wu S.-Y. J. Med. Chem. 49:2703-2712(2006) [PubMed: 16640330] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 235-505 IN COMPLEX WITH SYNTHETIC AGONIST.
[32]	"Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR-gamma) gene in diabetic Caucasians: identification of a pro12ala PPAR-gamma-2 missense mutation." Yen C.-J., Beamer B.A., Negri C., Silver K., Brown K.A., Yarnall D.P., Burns D.K., Roth J., Shuldiner A.R. Biochem. Biophys. Res. Commun. 241:270-274(1997) [PubMed: 9425261] [Abstract] Cited for: VARIANT ALA-12.
[33]	"Obesity associated with a mutation in a genetic regulator of adipocyte differentiation." Ristow M., Muller-Wieland D., Pfeiffer A., Krone W., Kahn C.R. N. Engl. J. Med. 339:953-959(1998) [PubMed: 9753710] [Abstract] Cited for: VARIANT OBESITY GLN-113.
[34]	"A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity." Deeb S.S., Fajas L., Nemoto M., Pihlajamaeki J., Mykkaenen L., Kuusisto J., Laakso M., Fujimoto W., Auwerx J. Nat. Genet. 20:284-287(1998) [PubMed: 9806549] [Abstract] Cited for: ASSOCIATION OF VARIANT ALA-12 WITH BMI.
[35]	"Missense variants in the human peroxisome proliferator-activated receptor-gamma2 gene in lean and obese subjects." Hamann A., Munzberg H., Buttron P., Busing B., Hinney A., Mayer H., Siegfried W., Hebebrand J., Greten H. Eur. J. Endocrinol. 141:90-92(1999) [PubMed: 10407229] [Abstract] Cited for: VARIANT ALA-12.
[36]	"Two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene are associated with severe overweight among obese women." Valve R., Sivenius K., Miettinen R., Pihlajamaeki J., Rissanen A., Deeb S.S., Auwerx J., Uusitupa M., Laakso M. J. Clin. Endocrinol. Metab. 84:3708-3712(1999) [PubMed: 10523018] [Abstract] Cited for: ASSOCIATION OF VARIANT ALA-12 WITH BMI.
[37]	"Loss-of-function mutations in PPAR-gamma associated with human colon cancer." Sarraf P., Mueller E., Smith W.M., Wright H.M., Kum J.B., Aaltonen L.A., de la Chapelle A., Spiegelman B.M., Eng C. Mol. Cell 3:799-804(1999) [PubMed: 10394368] [Abstract] Cited for: VARIANTS COLON CANCER PRO-314 AND HIS-316, VARIANT ALA-12.
[38]	"Dominant negative mutations in human PPAR-gamma associated with severe insulin resistance, diabetes mellitus and hypertension." Barroso I., Gurnell M., Crowley V.E.F., Agostini M., Schwabel J.W., Soos M.A., Masien G.L., Williams T.D.M., Lewis H., Schafer A.J., Chatterjee V.K.K., O'Rahilly S. Nature 402:880-883(1999) [PubMed: 10622252] [Abstract] Cited for: VARIANTS DIABETES MET-318 AND LEU-495.
[39]	"PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy." Hegele R.A., Cao H., Frankowski C., Mathews S.T., Leff T. Diabetes 51:3586-3590(2002) [PubMed: 12453919] [Abstract] Cited for: VARIANT FPLD3 LEU-388.
[40]	"A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy." Agarwal A.K., Garg A. J. Clin. Endocrinol. Metab. 87:408-411(2002) [PubMed: 11788685] [Abstract] Cited for: VARIANT FPLD3 CYS-425.
[41]	"Effect of the peroxisome proliferator activated receptor-gamma gene Pro12Ala variant on body mass index: a meta-analysis." Masud S., Ye S. J. Med. Genet. 40:773-780(2003) [PubMed: 14569127] [Abstract] Cited for: ASSOCIATION OF VARIANT ALA-12 WITH BMI.
[42]	"Ala12Ala genotype of the peroxisome proliferator-activated receptor gamma2 protects against atherosclerosis." Temelkova-Kurktschiev T., Hanefeld M., Chinetti G., Zawadzki C., Haulon S., Kubaszek A., Koehler C., Leonhardt W., Staels B., Laakso M. J. Clin. Endocrinol. Metab. 89:4238-4242(2004) [PubMed: 15356014] [Abstract] Cited for: ASSOCIATION OF VARIANT ALA-12 WITH CIMT.
[43]	"Effects of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala polymorphism on body fat distribution in female Korean subjects." Kim K.S., Choi S.M., Shin S.U., Yang H.S., Yoon Y. Metabolism 53:1538-1543(2004) [PubMed: 15562396] [Abstract] Cited for: VARIANT ALA-12.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Wikipedia

Peroxisome proliferator-activated receptor entry

GeneReviews

SeattleSNPs

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBLGenBankDDBJ

U79012 mRNA. Translation: AAC51248.1.
U63415 mRNA. Translation: AAB04028.1.
D83233 mRNA. Translation: BAA18949.1.
L40904 mRNA. Translation: AAA80314.2.
AB005526 Genomic DNA. Translation: BAA23354.1. Sequence problems.
X90563 mRNA. Translation: CAA62152.1.
X90563 mRNA. Translation: CAA62153.1. Different initiation.
BT007281 mRNA. Translation: AAP35945.1.
AK290581 mRNA. Translation: BAF83270.1. Different initiation.
AB451337 mRNA. Translation: BAG70151.1.
AB451486 mRNA. Translation: BAG70300.1.
AY157024 Genomic DNA. Translation: AAN38992.2. Different initiation.
AC090947 Genomic DNA. No translation available.
AC091492 Genomic DNA. No translation available.
AC093174 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64124.1.
BC006811 mRNA. Translation: AAH06811.1.

IPI

IPI00020897.
IPI00853091.

PIR

JC4859.
PC4290.
PC4429.

RefSeq

NP_056953.2.
NP_619725.2.
NP_619726.2.

UniGene

Hs.162646

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FM6	X-ray	2.10	D/X	234-505	[»]
1FM9	X-ray	2.10	D	234-505	[»]
1I7I	X-ray	2.35	A/B	225-505	[»]
1K74	X-ray	2.30	D	234-505	[»]
1KNU	X-ray	2.50	A/B	232-505	[»]
1NYX	X-ray	2.65	A/B	230-505	[»]
1PRG	X-ray	2.20	A/B	235-504	[»]
1RDT	X-ray	2.40	D	235-505	[»]
1WM0	X-ray	2.90	X	232-505	[»]
1ZEO	X-ray	2.50	A/B	231-505	[»]
1ZGY	X-ray	1.80	A	234-505	[»]
2ATH	X-ray	2.28	A/B	235-505	[»]
2F4B	X-ray	2.07	A/B	235-505	[»]
2FVJ	X-ray	1.99	A	235-505	[»]
2G0G	X-ray	2.54	A/B	235-505	[»]
2G0H	X-ray	2.30	A/B	235-505	[»]
2GTK	X-ray	2.10	A	235-505	[»]
2HFP	X-ray	2.00	A	234-505	[»]
2HWQ	X-ray	1.97	A/B	235-505	[»]
2HWR	X-ray	2.34	A/B	235-505	[»]
2I4J	X-ray	2.10	A/B	223-504	[»]
2I4P	X-ray	2.10	A/B	223-504	[»]
2I4Z	X-ray	2.25	A/B	223-504	[»]
2OM9	X-ray	2.80	A/B/C/D	232-505	[»]
2P4Y	X-ray	2.25	A/B	231-505	[»]
2POB	X-ray	2.30	A/B	234-505	[»]
2PRG	X-ray	2.30	A/B	235-505	[»]
2Q59	X-ray	2.20	A	233-505	[»]
			B	233-505	[»]
2Q5P	X-ray	2.30	A/B	233-505	[»]
2Q5S	X-ray	2.05	A/B	233-505	[»]
2Q61	X-ray	2.20	A/B	233-505	[»]
2Q6R	X-ray	2.41	A/B	233-505	[»]
2Q6S	X-ray	2.40	A/B	233-505	[»]
2Q8S	X-ray	2.30	A/B	235-505	[»]
2QMV	NMR	-	A	235-504	[»]
2VSR	X-ray	2.05	A/B	232-505	[»]
2VST	X-ray	2.35	A/B	232-505	[»]
2VV0	X-ray	2.55	A/B	232-505	[»]
2VV1	X-ray	2.20	A	232-505	[»]
			B	232-505	[»]
2VV2	X-ray	2.75	A/B	232-505	[»]
2VV3	X-ray	2.85	A/B	232-505	[»]
2VV4	X-ray	2.35	A	232-505	[»]
			B	232-505	[»]
2ZK0	X-ray	2.36	A/B	223-504	[»]
2ZK1	X-ray	2.61	A/B	223-504	[»]
2ZK2	X-ray	2.26	A/B	223-504	[»]
2ZK3	X-ray	2.58	A/B	223-504	[»]
2ZK4	X-ray	2.57	A/B	223-504	[»]
2ZK5	X-ray	2.45	A/B	223-504	[»]
2ZK6	X-ray	2.41	A/B	223-504	[»]
2ZNO	X-ray	2.40	A/B	223-504	[»]
3B3K	X-ray	2.60	A/B	223-504	[»]
3BC5	X-ray	2.27	A	231-505	[»]
3CDP	X-ray	2.80	A/B	223-504	[»]
3CDS	X-ray	2.65	A/B	223-504	[»]
3CS8	X-ray	2.30	A	234-504	[»]
3CWD	X-ray	2.40	A/B	236-505	[»]
3D6D	X-ray	2.40	A/B	223-504	[»]
3DZU	X-ray	3.20	D	102-505	[»]
3DZY	X-ray	3.10	D	102-505	[»]
3E00	X-ray	3.10	D	102-505	[»]
3ET0	X-ray	2.40	A/B	235-505	[»]
3ET3	X-ray	1.95	A	235-505	[»]
3PRG	X-ray	2.90	A	232-505	[»]
4PRG	X-ray	2.90	A/B/C/D	235-504	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P37231. 7 interactions.

PTM databases

PhosphoSite

P37231.

Proteomic databases

PRIDE

P37231.

Genome annotation databases

Ensembl

ENSG00000132170. Homo sapiens. [Contig view]

GeneID

5468.

Organism-specific databases

GeneCards

GC03P012305.

H-InvDB

HIX0003064.

HGNC

HGNC:9236. PPARG.

HPA

CAB004282.

MIM

601487. gene.
601665. phenotype.
604367. phenotype.
606641. phenotype.
609338. phenotype.

Orphanet

79083. Lipodystrophy, familial partial, associated with PPARG mutations.

PharmGKB

PA281.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P37231.

OMA

P37231. HLYDSYI.

Enzyme and pathway databases

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.

Gene expression databases

ArrayExpress

P37231.

Bgee

P37231.

GermOnline

ENSG00000132170. Homo sapiens.

Family and domain databases

InterPro

IPR003074. 1Cnucl_rcpt.
IPR003077. 1Cnucl_rcpt_G.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Gene3D

G3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 1 hit.
G3DSA:3.30.50.10. Znf_NHR/GATA. 1 hit.

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR01288. PROXISOMEPAR.
PR01291. PROXISOMPAGR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.

ProDom

PD000035. Znf_C4steroid. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01076. Atorvastatin.
DB00159. Icosapent.
DB01132. Pioglitazone.
DB00412. Rosiglitazone.
DB00197. Troglitazone.

NextBio

21164.

SOURCE

Search...

Entry information

Entry name

PPARG_HUMAN

Accession

Primary (citable) accession number: P37231
Secondary accession number(s): A8K3G6 , B5BUA1, O00684, O00710, O14515, Q15178, Q15179, Q15180, Q15832, Q86U60, Q96J12

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	April 27, 2001
Last modified:	June 16, 2009
This is version 137 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)