Q07869 (PPARA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Peroxisome proliferator-activated receptor alpha
Short name=PPAR-alpha

Alternative name(s):
Nuclear receptor subfamily 1 group C member 1

Gene names

Name:	PPARA
Synonyms:	NR1C1, PPAR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	468 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety By similarity. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. Ref.1 Ref.12 Ref.14 Ref.15
Subunit structure	Heterodimer; with RXRA. This heterodimerization is required for DNA binding and transactivation activity. Interacts with AKAP13, LPIN1 and PRDM16. Also interacts with PPARBP coactivator in vitro. Interacts with CITED2; the interaction stimulates its transcriptional activity By similarity. Interacts with NCOA3 and NCOA6 coactivators. Interacts with ASXL1 AND ASXL2. Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.19
Subcellular location	Nucleus.
Tissue specificity	Skeletal muscle, liver, heart and kidney. Ref.2 Ref.3
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Lipid-binding Metal-binding Zinc
Molecular function	Activator Receptor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	behavioral response to nicotine Inferred from electronic annotation. Source: Compara enamel mineralization Inferred from electronic annotation. Source: Compara epidermis development Inferred from electronic annotation. Source: Compara fatty acid metabolic process Traceable author statement PubMed 10377439. Source: ProtInc fatty acid transport Traceable author statement PubMed 16271724. Source: UniProtKB heart development Inferred from electronic annotation. Source: Compara lipoprotein metabolic process Inferred from electronic annotation. Source: Compara negative regulation of appetite Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of blood pressure Inferred from electronic annotation. Source: Compara negative regulation of cholesterol storage Inferred from direct assay PubMed 19114110. Source: BHF-UCL negative regulation of glycolysis Inferred by curator PubMed 19955185. Source: BHF-UCL negative regulation of macrophage derived foam cell differentiation Inferred from direct assay PubMed 19114110. Source: BHF-UCL negative regulation of neuron death Inferred from electronic annotation. Source: Compara negative regulation of protein binding Inferred from electronic annotation. Source: Compara negative regulation of receptor biosynthetic process Inferred from direct assay PubMed 12700342. Source: BHF-UCL negative regulation of sequestering of triglyceride Inferred from direct assay PubMed 12700342. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 12700342. Source: BHF-UCL negative regulation of transcription regulatory region DNA binding Inferred from electronic annotation. Source: Compara positive regulation of fatty acid beta-oxidation Traceable author statement PubMed 16271724. Source: UniProtKB regulation of cellular ketone metabolic process by positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19955185. Source: BHF-UCL regulation of glycolysis by positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19955185. Source: BHF-UCL regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19955185. Source: BHF-UCL response to hypoxia Inferred from electronic annotation. Source: Compara response to insulin stimulus Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	drug binding Inferred from direct assay Ref.18. Source: UniProtKB ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from direct assay Ref.18. Source: UniProtKB lipid binding Inferred from direct assay Ref.18. Source: UniProtKB sequence-specific DNA binding Inferred from sequence or structural similarity. Source: BHF-UCL steroid hormone receptor activity Inferred from direct assay PubMed 19955185. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CHD9	Q3L8U1-3	2	EBI-78615,EBI-960730

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 468

468

Peroxisome proliferator-activated receptor alpha

PRO_0000053481

Regions

DNA binding

99 – 173

75

Nuclear receptor

Zinc finger

102 – 122

21

NR C4-type

Zinc finger

139 – 161

23

NR C4-type

Region

280 – 468

189

Ligand-binding

Region

304 – 433

130

Required for heterodimerization with RXRA

Sites

Binding site

280

1

Synthetic agonist

Binding site

314

1

Synthetic agonist

Binding site

440

1

Synthetic agonist

Binding site

464

1

Synthetic agonist

Site

433

1

Essential for heterodimerization with RXRA

Natural variations

Natural variant

127

1

R → Q.
Corresponds to variant rs1800204 [ dbSNP | Ensembl ].

VAR_016110

Natural variant

162

1

L → V. Ref.9
Corresponds to variant rs1800206 [ dbSNP | Ensembl ].

VAR_016111

Natural variant

227

1

V → A.
Corresponds to variant rs1800234 [ dbSNP | Ensembl ].

VAR_016112

Natural variant

268

1

A → V. Ref.1
Corresponds to variant rs1042311 [ dbSNP | Ensembl ].

VAR_016113

Natural variant

304

1

D → N.
Corresponds to variant rs1800242 [ dbSNP | Ensembl ].

VAR_016114

Natural variant

395

1

G → R.
Corresponds to variant rs2229245 [ dbSNP | Ensembl ].

VAR_050578

Natural variant

409

1

R → T.
Corresponds to variant rs1800243 [ dbSNP | Ensembl ].

VAR_016115

Experimental info

Mutagenesis

122

1

C → G: Prevents DNA binding but no effect on heterodimerization with RXRA. Ref.12

Mutagenesis

304

1

D → A: Reduced heterodimerization with RXRA. Reduced DNA binding. Ref.15

Mutagenesis

370

1

L → R: Abolishes heterodimerization with RXRA. No DNA binding. Ref.15

Mutagenesis

391

1

L → R: Abolishes heterodimerization with RXRA. No DNA binding. Ref.15

Mutagenesis

422

1

L → R: No effect on heterodimerization with RXRA nor on DNA binding and transactivation activity. Ref.12

Mutagenesis

431

1

A → T: No effect on heterodimerization with RXRA nor on DNA binding. Ref.15

Mutagenesis

433

1

L → R: Abolishes heterodimerization with RXRA, DNA binding and transactivation activity. Ref.12

Sequence conflict

71

1

T → M in CAA68898. Ref.3

Sequence conflict

123

1

K → M in CAA68898. Ref.3

Sequence conflict

296

1

G → A in AAA36468. Ref.1

Sequence conflict

444

1

V → A in CAA68898. Ref.3

Secondary structure

1

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468

Helix Strand Turn

Details...

Helix

203 – 217

15

Helix

222 – 229

8

Beta strand

233 – 235

3

Beta strand

239 – 241

3

Helix

244 – 254

11

Helix

256 – 259

4

Helix

263 – 265

3

Helix

268 – 290

23

Helix

291 – 293

3

Turn

295 – 299

5

Helix

302 – 321

20

Helix

322 – 324

3

Beta strand

329 – 332

4

Turn

333 – 336

4

Beta strand

337 – 340

4

Helix

341 – 346

6

Turn

349 – 351

3

Helix

352 – 366

15

Helix

372 – 383

12

Helix

394 – 415

22

Helix

422 – 450

29

Beta strand

453 – 456

4

Helix

458 – 464

7

Turn

465 – 467

3

Sequences

	Sequence		Length	Mass (Da)
	Q07869 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 850846FD51ADA883	FASTA	468	52,225
	10 20 30 40 50 60 MVDTESPLCP LSPLEAGDLE SPLSEEFLQE MGNIQEISQS IGEDSSGSFG FTEYQYLGSC 70 80 90 100 110 120 PGSDGSVITD TLSPASSPSS VTYPVVPGSV DESPSGALNI ECRICGDKAS GYHYGVHACE 130 140 150 160 170 180 GCKGFFRRTI RLKLVYDKCD RSCKIQKKNR NKCQYCRFHK CLSVGMSHNA IRFGRMPRSE 190 200 210 220 230 240 KAKLKAEILT CEHDIEDSET ADLKSLAKRI YEAYLKNFNM NKVKARVILS GKASNNPPFV 250 260 270 280 290 300 IHDMETLCMA EKTLVAKLVA NGIQNKEAEV RIFHCCQCTS VETVTELTEF AKAIPGFANL 310 320 330 340 350 360 DLNDQVTLLK YGVYEAIFAM LSSVMNKDGM LVAYGNGFIT REFLKSLRKP FCDIMEPKFD 370 380 390 400 410 420 FAMKFNALEL DDSDISLFVA AIICCGDRPG LLNVGHIEKM QEGIVHVLRL HLQSNHPDDI 430 440 450 460 FLFPKLLQKM ADLRQLVTEH AQLVQIIKKT ESDAALHPLL QEIYRDMY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor." Sher T., Yi H.F., McBride O.W., Gonzales F.J. Biochemistry 32:5598-5604(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANT VAL-268. Tissue: Liver.
[2]	"Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators." Mukherjee R., Jow L., Noonan D., McDonnell D.P. J. Steroid Biochem. Mol. Biol. 51:157-166(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Liver.
[3]	"Peroxisome proliferator-activated receptors: structures and function." Tugwood J.D., Aldridge T.C., Lambe K.G., Macdonald N., Woodyatt N.J. Ann. N. Y. Acad. Sci. 804:252-265(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[4]	"DNA-binding profiling of human hormone nuclear receptors via fluorescence correlation spectroscopy in a cell-free system." Kobayashi T., Kodani Y., Nozawa A., Endo Y., Sawasaki T. FEBS Lett. 582:2737-2744(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Optimization of an enzyme-linked immunosorbent assay to screen ligand of Peroxisome proliferator-activated receptor alpha." Cho M.-C., Lee S., Choi H.S., Yang Y., Tae Hong J., Kim S.J., Yoon D.-Y. Immunopharmacol. Immunotoxicol. 31:459-467(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[8]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	SeattleSNPs variation discovery resource Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-162.
[10]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	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].
[12]	"Peroxisome proliferator-activated receptor mediates cross-talk with thyroid hormone receptor by competition for retinoid X receptor. Possible role of a leucine zipper-like heptad repeat." Juge-Aubry C.E., Gorla-Bajszczak A., Pernin A., Lemberger T., Wahli W., Burger A.G., Meier C.A. J. Biol. Chem. 270:18117-18122(1995) [PubMed] [Europe PMC] [Abstract] Cited for: HETERODIMERIZATION WITH RXRA, FUNCTION, MUTAGENESIS OF CYS-122; LEU-422 AND LEU-433.
[13]	"RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2." Li H., Gomes P.J., Chen J.D. Proc. Natl. Acad. Sci. U.S.A. 94:8479-8484(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCOA3.
[14]	"Regulation of peroxisome proliferator-activated receptor alpha-induced transactivation by the nuclear orphan receptor TAK1/TR4." Yan Z.H., Karam W.G., Staudinger J.L., Medvedev A., Ghanayem B.I., Jetten A.M. J. Biol. Chem. 273:10948-10957(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"Conserved amino acids in the ligand-binding and tau(i) domains of the peroxisome proliferator-activated receptor alpha are necessary for heterodimerization with RXR." Gorla-Bajszczak A., Juge-Aubry C., Pernin A., Burger A.G., Meier C.A. Mol. Cell. Endocrinol. 147:37-47(1999) [PubMed] [Europe PMC] [Abstract] Cited for: HETERODIMERIZATION WITH RXRA, FUNCTION, MUTAGENESIS OF ASP-304; LEU-370; LEU-391 AND ALA-431.
[16]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCOA6.
[17]	"Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity." Tsutsumi T., Suzuki T., Shimoike T., Suzuki R., Moriya K., Shintani Y., Fujie H., Matsuura Y., Koike K., Miyamura T. Hepatology 35:937-946(2002) [PubMed] [Europe PMC] [Abstract] Cited for: HETERODIMERIZATION WITH RXRA.
[18]	"Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha." Fu J., Gaetani S., Oveisi F., Lo Verme J., Serrano A., Rodriguez De Fonseca F., Rosengarth A., Luecke H., Di Giacomo B., Tarzia G., Piomelli D. Nature 425:90-93(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS RECEPTOR FOR OLEYLETHANOLAMIDE.
[19]	"Additional sex comb-like (ASXL) proteins 1 and 2 play opposite roles in adipogenesis via reciprocal regulation of peroxisome proliferator-activated receptor {gamma}." Park U.H., Yoon S.K., Park T., Kim E.J., Um S.J. J. Biol. Chem. 286:1354-1363(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ASXL1 AND ASXL2.
[20]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 192-468 IN COMPLEX WITH SYNTHETIC AGONIST.
[21]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 196-468 IN COMPLEX WITH SYNTHETIC AGONIST.
[22]	"Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha." Xu H.E., Stanley T.B., Montana V.G., Lambert M.H., Shearer B.G., Cobb J.E., McKee D.D., Galardi C.M., Plunket K.D., Nolte R.T., Parks D.J., Moore J.T., Kliewer S.A., Willson T.M., Stimmel J.B. Nature 415:813-817(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 200-468 IN COMPLEX WITH SYNTHETIC AGONIST.
[23]	"Design and synthesis of oxime ethers of alpha-acyl-beta-phenylpropanoic acids as PPAR dual agonists." Oon Han H., Kim S.H., Kim K.-H., Hur G.-C., Joo Yim H., Chung H.-K., Ho Woo S., Dong Koo K., Lee C.-S., Sung Koh J., Kim G.T. Bioorg. Med. Chem. Lett. 17:937-941(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 199-468 IN COMPLEX WITH SYNTHETIC AGONIST.
[24]	"Substituted 2-[(4-aminomethyl)phenoxy]-2-methylpropionic acid PPARalpha agonists. 1. Discovery of a novel series of potent HDLc raising agents." Sierra M.L., Beneton V., Boullay A.-B., Boyer T., Brewster A.G., Donche F., Forest M.-C., Fouchet M.-H., Gellibert F.J., Grillot D.A., Lambert M.H., Laroze A., Le Grumelec C., Linget J.M., Montana V.G., Nguyen V.-L., Nicodeme E., Patel V. , Penfornis A., Pineau O., Pohin D., Potvain F., Poulain G., Ruault C.B., Saunders M., Toum J., Xu H.E., Xu R.X., Pianetti P.M. J. Med. Chem. 50:685-695(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 202-468 IN COMPLEX WITH SYNTHETIC AGONIST.
[25]	"Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures." Oyama T., Toyota K., Waku T., Hirakawa Y., Nagasawa N., Kasuga J.I., Hashimoto Y., Miyachi H., Morikawa K. Acta Crystallogr. D 65:786-795(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 200-468 IN COMPLEX WITH THE SYNTHETIC AGONIST TIPP-703.
[26]	"Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes." Benardeau A., Benz J., Binggeli A., Blum D., Boehringer M., Grether U., Hilpert H., Kuhn B., Maerki H.P., Meyer M., Puentener K., Raab S., Ruf A., Schlatter D., Mohr P. Bioorg. Med. Chem. Lett. 19:2468-2473(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 199-468 IN COMPLEX WITH ALEGLITAZAR.
[27]	"Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent." Artis D.R., Lin J.J., Zhang C., Wang W., Mehra U., Perreault M., Erbe D., Krupka H.I., England B.P., Arnold J., Plotnikov A.N., Marimuthu A., Nguyen H., Will S., Signaevsky M., Kral J., Cantwell J., Settachatgull C. , Yan D.S., Fong D., Oh A., Shi S., Womack P., Powell B., Habets G., West B.L., Zhang K.Y.J., Milburn M.V., Vlasuk G.P., Hirth K.P., Nolop K., Bollag G., Ibrahim P.N., Tobin J.F. Proc. Natl. Acad. Sci. U.S.A. 106:262-267(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 199-468 IN COMPLEX WITH INDEGLITAZAR.
+	Additional computationally mapped references.

Web resources

Wikipedia

Peroxisome proliferator-activated receptor entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L02932 mRNA. Translation: AAA36468.1.
S74349 mRNA. Translation: AAB32649.1.
Y07619 mRNA. Translation: CAA68898.1.
AB307690 mRNA. Translation: BAH02281.1.
EU650667 mRNA. Translation: ACD12656.1.
CR456547 mRNA. Translation: CAG30433.1.
AK289821 mRNA. Translation: BAF82510.1.
CR457435 mRNA. Translation: CAG33716.1.
AY206718 Genomic DNA. Translation: AAO13489.1.
AL049856, AL078611 Genomic DNA. Translation: CAI22450.1.
CH471138 Genomic DNA. Translation: EAW73402.1.

IPI

IPI00020097.

PIR

A49289.
I56603.

RefSeq

NP_001001928.1. NM_001001928.2.
NP_005027.2. NM_005036.4.

UniGene

Hs.103110.
Hs.710044.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1I7G	X-ray	2.20	A	196-468	[»]
1K7L	X-ray	2.50	A/C/E/G	192-468	[»]
1KKQ	X-ray	3.00	A/B/C/D	200-468	[»]
2NPA	X-ray	2.30	A/C	199-468	[»]
2P54	X-ray	1.79	A	202-468	[»]
2REW	X-ray	2.35	A	196-468	[»]
2ZNN	X-ray	2.01	A	200-468	[»]
3ET1	X-ray	2.50	A/B	199-468	[»]
3FEI	X-ray	2.40	A	202-468	[»]
3G8I	X-ray	2.20	A	199-468	[»]
3KDT	X-ray	2.70	A/B	196-468	[»]
3KDU	X-ray	2.07	A/B	196-468	[»]
3SP6	X-ray	2.21	A	196-468	[»]
3VI8	X-ray	1.75	A	200-468	[»]

ProteinModelPortal

Q07869.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-241N.

IntAct

Q07869. 7 interactions.

MINT

MINT-232229.

STRING

9606.ENSP00000262735.

PTM databases

PhosphoSite

Q07869.

Polymorphism databases

DMDM

3041727.

Proteomic databases

PaxDb

Q07869.

PRIDE

Q07869.

Protocols and materials databases

DNASU

5465.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262735; ENSP00000262735; ENSG00000186951.
ENST00000396000; ENSP00000379322; ENSG00000186951.
ENST00000402126; ENSP00000385246; ENSG00000186951.
ENST00000407236; ENSP00000385523; ENSG00000186951.

GeneID

5465.

KEGG

hsa:5465.

UCSC

uc003bgw.1. human.

Organism-specific databases

CTD

5465.

GeneCards

GC22P046546.

HGNC

HGNC:9232. PPARA.

MIM

170998. gene+phenotype.

neXtProt

NX_Q07869.

PharmGKB

PA280.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG266867.

HOGENOM

HOG000261626.

HOVERGEN

HBG106004.

InParanoid

Q07869.

KO

K07294.

OMA

ICPLSPL.

OrthoDB

EOG4FFD1Q.

PhylomeDB

Q07869.

Enzyme and pathway databases

Pathway_Interaction_DB

rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.

Reactome

REACT_111217. Metabolism.
REACT_24941. Circadian Clock.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q07869.

Bgee

Q07869.

CleanEx

HS_PPARA.

Genevestigator

Q07869.

GermOnline

ENSG00000186951. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 2 hits.
3.30.50.10. 1 hit.

InterPro

IPR003074. 1Cnucl_rcpt.
IPR003076. 1Cnucl_rcpt_A.
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]

Pfam

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

PRINTS

PR01288. PROXISOMEPAR.
PR01289. PROXISOMPAAR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.

SMART

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

SUPFAM

SSF48508. Str_ncl_receptor. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

BindingDB

Q07869.

ChEMBL

CHEMBL239.

DrugBank

DB01076. Atorvastatin.
DB01393. Bezafibrate.
DB00636. Clofibrate.
DB01039. Fenofibrate.
DB01241. Gemfibrozil.
DB00641. Simvastatin.

EvolutionaryTrace

Q07869.

GenomeRNAi

5465.

NextBio

21152.

SOURCE

Search...

Entry information

Entry name

PPARA_HUMAN

Accession

Primary (citable) accession number: Q07869
Secondary accession number(s): Q16241 , Q6I9S0, Q92486, Q92689, Q9Y3N1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 160 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.