Swiss-Prot entry
ID PPAT_HUMAN STANDARD; PRT; 505 AA.
AC P37231; O00684; O00710; O14515; Q15178; Q15179; Q15180; Q15832;
AC Q86U60; Q96J12;
DT 01-OCT-1994 (Rel. 30, Created)
DT 16-OCT-2001 (Rel. 40, Last sequence update)
DT 01-MAY-2005 (Rel. 47, Last annotation update)
DE Peroxisome proliferator activated receptor gamma (PPAR-gamma).
GN Name=PPARG; Synonyms=NR1C3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2), AND CHARACTERIZATION.
RC TISSUE=Heart;
RX MEDLINE=97218249; PubMed=9065481 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.272.12.8071;
RA Mukherjee R., Jow L., Croston G.E., Paterniti J.R. Jr.;
RT "Identification, characterization, and tissue distribution of human
RT peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2
RT versus PPARgamma1 and activation with retinoid X receptor agonists and
RT antagonists.";
RL J. Biol. Chem. 272:8071-8076(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2).
RC TISSUE=Fat body;
RX MEDLINE=96295505; PubMed=8702406 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1006/bbrc.1996.1044;
RA Elbrecht A., Chen Y., Cullinan C.A., Hayes N., Leibowitz M.D.,
RA Moller D.E., Berger J.;
RT "Molecular cloning, expression and characterization of human
RT peroxisome proliferator activated receptors gamma 1 and gamma 2.";
RL Biochem. Biophys. Res. Commun. 224:431-437(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM 2).
RC TISSUE=Adipose tissue;
RX MEDLINE=97289627; PubMed=9144532 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1006/bbrc.1997.6446;
RA Yanase T., Yashiro T., Takitani K., Kato S., Taniguchi S.,
RA Takayanagi R., Nawata H.;
RT "Differential expression of PPAR gamma1 and gamma2 isoforms in human
RT adipose tissue.";
RL Biochem. Biophys. Res. Commun. 233:320-324(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RC TISSUE=Bone marrow;
RX MEDLINE=95307078; PubMed=7787419 [NCBI, ExPASy, EBI, Israel, Japan];
RA Greene M.E., Blumberg B., McBride O.W., Yi H.F., Kronquist K.,
RA Kwan K., Hsieh L., Greene G., Nimer S.D.;
RT "Isolation of the human peroxisome proliferator activated receptor
RT gamma cDNA: expression in hematopoietic cells and chromosomal
RT mapping.";
RL Gene Expr. 4:281-299(1995).
RN [5]
RP SEQUENCE REVISION TO 36; 37; 213; 214 AND 240.
RA Greene M.E.;
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RC TISSUE=Placenta;
RX MEDLINE=98016122; PubMed=9356045 [NCBI, ExPASy, EBI, Israel, Japan];
RA Okazawa H., Mori H., Tamori Y., Araki S., Niki T., Masugi J.,
RA Kawanishi M., Kubota T., Shinoda H., Kasuga M.;
RT "No coding mutations are detected in the peroxisome proliferator-
RT activated receptor-gamma gene in Japanese patients with lipoatrophic
RT diabetes.";
RL Diabetes 46:1904-1906(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RC TISSUE=Placenta;
RX MEDLINE=96305359; PubMed=8706692 [NCBI, ExPASy, EBI, Israel, Japan];
RA Lambe K.G., Tugwood J.D.;
RT "A human peroxisome-proliferator-activated receptor-gamma is activated
RT by inducers of adipogenesis, including thiazolidinedione drugs.";
RL Eur. J. Biochem. 239:1-7(1996).
RN [8]
RP NUCLEOTIDE SEQUENCE (ISOFORM 2), AND VARIANT ALA-12.
RA Rieder M.J., da Ponte S.H., Kuldanek S.A., Rajkumar N., Smith J.D.,
RA Toth E.J., Nickerson D.A.;
RT "SeattleSNPs. NHLBI HL66682 program for genomic applications, UW-
RT FHCRC, Seattle, WA (URL: http://pga.gs.washington.edu).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX MEDLINE=22388257; PubMed=12477932 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [11]
RP INTERACTION WITH NCOA6.
RX MEDLINE=20148724; PubMed=10681503 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1074/jbc.275.8.5308;
RA Caira F., Antonson P., Pelto-Huikko M., Treuter E., Gustafsson J.-A.;
RT "Cloning and characterization of RAP250, a nuclear receptor
RT coactivator.";
RL J. Biol. Chem. 275:5308-5317(2000).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX MEDLINE=20337987; PubMed=10882139 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1016/S1097-2765(00)80448-7;
RA Gampe R.T. Jr., Montana V.G., Lambert M.H., Miller A.B., Bledsoe R.K.,
RA Milburn M.V., Kliewer S.A., Willson T.M., Xu H.E.;
RT "Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the
RT molecular basis of heterodimerization among nuclear receptors.";
RL Mol. Cell 5:545-555(2000).
RN [13]
RP VARIANT ALA-12.
RX MEDLINE=98086341; PubMed=9425261 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1006/bbrc.1997.7798;
RA Yen C.-J., Beamer B.A., Negri C., Silver K., Brown K.A., Yarnall D.P.,
RA Burns D.K., Roth J., Shuldiner A.R.;
RT "Molecular scanning of the human peroxisome proliferator activated
RT receptor gamma (hPPAR-gamma) gene in diabetic Caucasians:
RT identification of a pro12ala PPAR-gamma-2 missense mutation.";
RL Biochem. Biophys. Res. Commun. 241:270-274(1997).
RN [14]
RP VARIANT OBESITY GLN-113.
RX MEDLINE=98418646; PubMed=9753710 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1056/NEJM199810013391403;
RA Ristow M., Muller-Wieland D., Pfeiffer A., Krone W., Kahn C.R.;
RT "Obesity associated with a mutation in a genetic regulator of
RT adipocyte differentiation.";
RL N. Engl. J. Med. 339:953-959(1998).
RN [15]
RP VARIANT ALA-12.
RX MEDLINE=99337654; PubMed=10407229 [NCBI, ExPASy, EBI, Israel, Japan];
RA Hamann A., Munzberg H., Buttron P., Busing B., Hinney A., Mayer H.,
RA Siegfried W., Hebebrand J., Greten H.;
RT "Missense variants in the human peroxisome proliferator-activated
RT receptor-gamma2 gene in lean and obese subjects.";
RL Eur. J. Endocrinol. 141:90-92(1999).
RN [16]
RP VARIANTS COLON CANCER PRO-314 AND HIS-316, AND VARIANT ALA-12.
RX MEDLINE=99322672; PubMed=10394368 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1016/S1097-2765(01)80012-5;
RA Sarraf P., Mueller E., Smith W.M., Wright H.M., Kum J.B.,
RA Aaltonen L.A., de la Chapelle A., Spiegelman B.M., Eng C.;
RT "Loss-of-function mutations in PPAR-gamma associated with human colon
RT cancer.";
RL Mol. Cell 3:799-804(1999).
RN [17]
RP VARIANTS DIABETES MET-318 AND LEU-495.
RX MEDLINE=20085964; PubMed=10622252 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1038/47254;
RA Barroso I., Gurnell M., Crowley V.E.F., Agostini M., Schwabel J.W.,
RA Soos M.A., Masien G.L., Williams T.D.M., Lewis H., Schafer A.J.,
RA Chatterjee V.K.K., O'Rahilly S.;
RT "Dominant negative mutations in human PPAR-gamma associated with
RT severe insulin resistance, diabetes mellitus and hypertension.";
RL Nature 402:880-883(1999).
CC -!- FUNCTION: Receptor that binds peroxisome proliferators such as
CC hypolipidemic drugs and fatty acids. Once activated by a ligand,
CC the receptor binds to a promoter element in the gene for acyl-CoA
CC oxidase and activates its transcription. It therefore controls the
CC peroxisomal beta-oxidation pathway of fatty acids. Key regulator
CC of adipocyte differentiation and glucose homeostasis.
CC -!- SUBUNIT: Forms a heterodimer with the retinoic acid receptor RXR-
CC alpha called adipocyte-specific transcription factor ARF6.
CC Interacts with NCOA6 coactivator, leading to a strong increase in
CC transcription of target genes (By similarity).
CC -!- SUBCELLULAR LOCATION: Nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist;
CC Name=2;
CC IsoId=P37231-1; Sequence=Displayed;
CC Name=1;
CC IsoId=P37231-2; Sequence=VSP_003645;
CC -!- TISSUE SPECIFICITY: Highest expression in adipose tissue. Lower in
CC skeletal muscle, spleen, heart and liver. Also are detectable in
CC placenta, lung and ovary.
CC -!- DISEASE: Defects in PPARG can lead to type 2 insulin-resistant
CC diabetes and hyptertension.
CC -!- DISEASE: Defects in PPARG could play a role in the genetic
CC predisposition to obesity.
CC -!- DISEASE: Defects in PPARG may be associated with colon cancer.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily.
CC -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
CC --------------------------------------------------------------------------
CC This Swiss-Prot entry is copyright. It is produced through a collaboration
CC between the Swiss Institute of Bioinformatics and the EMBL outstation -
CC the European Bioinformatics Institute. There are no restrictions on its
CC use as long as its content is in no way modified and this statement is not
CC removed.
CC --------------------------------------------------------------------------
DR EMBL; U79012; AAC51248.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; U63415; AAB04028.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; D83233; BAA18949.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; L40904; AAA80314.2; ALT_INIT. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AB005526; BAA23354.1; ALT_INIT. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AB005521; BAA23354.1; JOINED. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AB005522; BAA23354.1; JOINED. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AB005523; BAA23354.1; JOINED. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AB005524; BAA23354.1; JOINED. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AB005525; BAA23354.1; JOINED. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; X90563; CAA62152.1; ALT_INIT. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; X90563; CAA62153.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AY157024; AAN38992.2; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; BT007281; AAP35945.1; ALT_INIT. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; BC006811; AAH06811.1; ALT_INIT. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR PDB; 1FM6; X-ray; D/X=234-505. [ExPASy / RCSB]
DR PDB; 1FM9; X-ray; D=234-505. [ExPASy / RCSB]
DR PDB; 1I7I; X-ray; A/B=214-505. [ExPASy / RCSB]
DR PDB; 1K74; X-ray; D=223-505. [ExPASy / RCSB]
DR PDB; 1NYX; X-ray; A/B=230-505. [ExPASy / RCSB]
DR PDB; 1PRG; X-ray; A/B=235-503. [ExPASy / RCSB]
DR PDB; 2PRG; X-ray; A/B=235-505. [ExPASy / RCSB]
DR PDB; 3PRG; X-ray; A=228-505. [ExPASy / RCSB]
DR PDB; 4PRG; X-ray; A/B/C/D=235-503. [ExPASy / RCSB]
DR TRANSFAC; T03731; -.
DR Ensembl; ENSG00000132170; Homo_sapiens
DR Genew; HGNC:9236; PPARG.
DR CleanEx; HGNC:9236; PPARG.
DR H-InvDB; HIX0003064; -.
DR MIM; 601487; -. [NCBI / EBI]
DR GeneCards; PPARG.
DR GeneLynx; PPARG.
DR GenAtlas; PPARG.
DR SOURCE; PPARG.
DR MIM; 604367; -. [NCBI / EBI]
DR GO; GO:0004879; F:ligand-dependent nuclear receptor activity; TAS.
DR GO; GO:0003700; F:transcription factor activity; TAS.
DR GO; GO:0006091; P:energy pathways; TAS.
DR GO; GO:0006629; P:lipid metabolism; TAS.
DR GO; GO:0006357; P:regulation of transcription from Pol II pro...; TAS.
DR GO; GO:0007584; P:response to nutrients; TAS.
DR GO; GO:0007165; P:signal transduction; TAS.
DR GO; GO:0050872; P:white adipocyte differentiation; TAS.
DR InterPro; IPR000536; Hrmon_recept_lig.
DR InterPro; IPR001723; Stdhrmn_receptor.
DR InterPro; IPR008946; Str_ncl_receptor.
DR InterPro; IPR001628; Znf_C4steroid.
DR InterPro; Graphical view of domain structure.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR Pfam; Graphical view of domain structure.
DR PRINTS; PR01288; PROXISOMEPAR.
DR PRINTS; PR01291; PROXISOMPAGR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR ProDom; PD000035; Znf_C4steroid; 1.
DR ProDom [Domain structure / List of seq. sharing at least 1 domain ]
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
DR CMR; P37231.
DR HOVERGEN [Family / Alignment / Tree]
DR BLOCKS; P37231.
DR ProtoNet; P37231.
DR ProtoMap; P37231.
DR PRESAGE; P37231.
DR DIP; P37231.
DR ModBase; P37231.
DR SWISS-2DPAGE; GET REGION ON 2D PAGE.
KW 3D-structure; Activator; Alternative splicing; Diabetes mellitus;
KW Disease mutation; DNA-binding; Multigene family; Nuclear protein;
KW Obesity; Phosphorylation; Polymorphism; Receptor; Transcription;
KW Transcription regulation; Zinc-finger.
FT DNA_BIND 136 210 Nuclear receptor-type.
FT ZN_FING 139 159 C4-type.
FT ZN_FING 176 198 C4-type.
FT DOMAIN 318 505 Ligand-binding (Potential).
FT MOD_RES 112 112 Phosphoserine (by MAPK) (By similarity).
FT VARSPLIC 1 30 Missing (in isoform 1).
FT /FTId=VSP_003645.
FT VARIANT 12 12 P -> A (in dbSNP:1801282).
FT /FTId=VAR_010723.
FT VARIANT 40 40 P -> A (in dbSNP:1805192).
FT /FTId=VAR_016116.
FT VARIANT 113 113 P -> Q (in obesity; dbSNP:1800571).
FT /FTId=VAR_010724.
FT VARIANT 314 314 Q -> P (in colon cancer; sporadic;
FT somatic mutation; loss of ligand-
FT binding).
FT /FTId=VAR_010725.
FT VARIANT 316 316 R -> H (in colon cancer; sporadic;
FT somatic mutation; partial loss of ligand-
FT binding).
FT /FTId=VAR_010726.
FT VARIANT 318 318 V -> M (in diabetes).
FT /FTId=VAR_010727.
FT VARIANT 495 495 P -> L (in diabetes).
FT /FTId=VAR_010728.
FT CONFLICT 36 37 MP -> IA (in Ref. 3).
FT CONFLICT 213 214 MP -> IA (in Ref. 3).
FT CONFLICT 240 240 R -> RQ (in Ref. 3).
FT CONFLICT 424 426 Missing (in Ref. 6).
FT HELIX 236 253
FT HELIX 258 265
FT TURN 267 268
FT STRAND 275 277
FT HELIX 280 285
FT TURN 286 288
FT TURN 301 303
FT HELIX 305 329
FT TURN 330 330
FT TURN 332 333
FT HELIX 334 336
FT HELIX 339 360
FT TURN 361 361
FT STRAND 362 363
FT TURN 364 365
FT STRAND 366 369
FT HELIX 370 372
FT TURN 373 373
FT STRAND 374 377
FT HELIX 378 382
FT TURN 383 383
FT TURN 386 386
FT HELIX 387 390
FT HELIX 393 403
FT TURN 404 405
FT HELIX 409 420
FT TURN 421 421
FT TURN 426 427
FT HELIX 431 452
FT TURN 454 455
FT TURN 457 458
FT HELIX 459 465
FT TURN 466 466
FT HELIX 467 487
FT TURN 489 490
FT HELIX 495 499
SQ SEQUENCE 505 AA; 57620 MW; 3933EFF36A0E4CAF CRC64;
MGETLGDSPI DPESDSFTDT LSANISQEMT MVDTEMPFWP TNFGISSVDL SVMEDHSHSF
DIKPFTTVDF SSISTPHYED IPFTRTDPVV ADYKYDLKLQ EYQSAIKVEP ASPPYYSEKT
QLYNKPHEEP SNSLMAIECR VCGDKASGFH YGVHACEGCK GFFRRTIRLK LIYDRCDLNC
RIHKKSRNKC QYCRFQKCLA VGMSHNAIRF GRMPQAEKEK LLAEISSDID QLNPESADLR
ALAKHLYDSY IKSFPLTKAK ARAILTGKTT DKSPFVIYDM NSLMMGEDKI KFKHITPLQE
QSKEVAIRIF QGCQFRSVEA VQEITEYAKS IPGFVNLDLN DQVTLLKYGV HEIIYTMLAS
LMNKDGVLIS EGQGFMTREF LKSLRKPFGD FMEPKFEFAV KFNALELDDS DLAIFIAVII
LSGDRPGLLN VKPIEDIQDN LLQALELQLK LNHPESSQLF AKLLQKMTDL RQIVTEHVQL
LQVIKKTETD MSLHPLLQEI YKDLY
//