PPARA_HUMAN
ID PPARA_HUMAN Reviewed; 468 AA.
AC Q07869; B0G0X3; Q16241; Q6I9S0; Q92486; Q92689; Q9Y3N1;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 242.
DE RecName: Full=Peroxisome proliferator-activated receptor alpha;
DE Short=PPAR-alpha;
DE AltName: Full=Nuclear receptor subfamily 1 group C member 1;
GN Name=PPARA; Synonyms=NR1C1, PPAR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND VARIANT VAL-268.
RC TISSUE=Liver;
RX PubMed=7684926; DOI=10.1021/bi00072a015;
RA Sher T., Yi H.F., McBride O.W., Gonzales F.J.;
RT "cDNA cloning, chromosomal mapping, and functional characterization of the
RT human peroxisome proliferator activated receptor.";
RL Biochemistry 32:5598-5604(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=7981125; DOI=10.1016/0960-0760(94)90089-2;
RA Mukherjee R., Jow L., Noonan D., McDonnell D.P.;
RT "Human and rat peroxisome proliferator activated receptors (PPARs)
RT demonstrate similar tissue distribution but different responsiveness to
RT PPAR activators.";
RL J. Steroid Biochem. Mol. Biol. 51:157-166(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=8993548; DOI=10.1111/j.1749-6632.1996.tb18620.x;
RA Tugwood J.D., Aldridge T.C., Lambe K.G., Macdonald N., Woodyatt N.J.;
RT "Peroxisome proliferator-activated receptors: structures and function.";
RL Ann. N. Y. Acad. Sci. 804:252-265(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=18619963; DOI=10.1016/j.febslet.2008.07.003;
RA Kobayashi T., Kodani Y., Nozawa A., Endo Y., Sawasaki T.;
RT "DNA-binding profiling of human hormone nuclear receptors via fluorescence
RT correlation spectroscopy in a cell-free system.";
RL FEBS Lett. 582:2737-2744(2008).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=19263263; DOI=10.1080/08923970902785246;
RA Cho M.-C., Lee S., Choi H.S., Yang Y., Tae Hong J., Kim S.J., Yoon D.-Y.;
RT "Optimization of an enzyme-linked immunosorbent assay to screen ligand of
RT Peroxisome proliferator-activated receptor alpha.";
RL Immunopharmacol. Immunotoxicol. 31:459-467(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Jiang Y., Xie Z., Liu H., Liu M., Liu F.;
RT "A novel alternatively spliced peroxisome proliferator-activated receptor
RT alpha.";
RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-162.
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP HETERODIMERIZATION WITH RXRA, FUNCTION, AND MUTAGENESIS OF CYS-122; LEU-422
RP AND LEU-433.
RX PubMed=7629123; DOI=10.1074/jbc.270.30.18117;
RA Juge-Aubry C.E., Gorla-Bajszczak A., Pernin A., Lemberger T., Wahli W.,
RA Burger A.G., Meier C.A.;
RT "Peroxisome proliferator-activated receptor mediates cross-talk with
RT thyroid hormone receptor by competition for retinoid X receptor. Possible
RT role of a leucine zipper-like heptad repeat.";
RL J. Biol. Chem. 270:18117-18122(1995).
RN [14]
RP INTERACTION WITH NCOA3.
RX PubMed=9238002; DOI=10.1073/pnas.94.16.8479;
RA Li H., Gomes P.J., Chen J.D.;
RT "RAC3, a steroid/nuclear receptor-associated coactivator that is related to
RT SRC-1 and TIF2.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:8479-8484(1997).
RN [15]
RP FUNCTION.
RX PubMed=9556573; DOI=10.1074/jbc.273.18.10948;
RA Yan Z.H., Karam W.G., Staudinger J.L., Medvedev A., Ghanayem B.I.,
RA Jetten A.M.;
RT "Regulation of peroxisome proliferator-activated receptor alpha-induced
RT transactivation by the nuclear orphan receptor TAK1/TR4.";
RL J. Biol. Chem. 273:10948-10957(1998).
RN [16]
RP HETERODIMERIZATION WITH RXRA, FUNCTION, AND MUTAGENESIS OF ASP-304;
RP LEU-370; LEU-391 AND ALA-431.
RX PubMed=10195690; DOI=10.1016/s0303-7207(98)00217-2;
RA Gorla-Bajszczak A., Juge-Aubry C., Pernin A., Burger A.G., Meier C.A.;
RT "Conserved amino acids in the ligand-binding and tau(i) domains of the
RT peroxisome proliferator-activated receptor alpha are necessary for
RT heterodimerization with RXR.";
RL Mol. Cell. Endocrinol. 147:37-47(1999).
RN [17]
RP INTERACTION WITH NCOA6.
RX PubMed=10681503; 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 coactivator.";
RL J. Biol. Chem. 275:5308-5317(2000).
RN [18]
RP HETERODIMERIZATION WITH RXRA.
RX PubMed=11915042; DOI=10.1053/jhep.2002.32470;
RA Tsutsumi T., Suzuki T., Shimoike T., Suzuki R., Moriya K., Shintani Y.,
RA Fujie H., Matsuura Y., Koike K., Miyamura T.;
RT "Interaction of hepatitis C virus core protein with retinoid X receptor
RT alpha modulates its transcriptional activity.";
RL Hepatology 35:937-946(2002).
RN [19]
RP IDENTIFICATION AS RECEPTOR FOR OLEYLETHANOLAMIDE.
RX PubMed=12955147; DOI=10.1038/nature01921;
RA Fu J., Gaetani S., Oveisi F., Lo Verme J., Serrano A.,
RA Rodriguez De Fonseca F., Rosengarth A., Luecke H., Di Giacomo B.,
RA Tarzia G., Piomelli D.;
RT "Oleylethanolamide regulates feeding and body weight through activation of
RT the nuclear receptor PPAR-alpha.";
RL Nature 425:90-93(2003).
RN [20]
RP INTERACTION WITH ASXL1 AND ASXL2.
RX PubMed=21047783; DOI=10.1074/jbc.m110.177816;
RA Park U.H., Yoon S.K., Park T., Kim E.J., Um S.J.;
RT "Additional sex comb-like (ASXL) proteins 1 and 2 play opposite roles in
RT adipogenesis via reciprocal regulation of peroxisome proliferator-activated
RT receptor {gamma}.";
RL J. Biol. Chem. 286:1354-1363(2011).
RN [21]
RP INTERACTION WITH SIRT1, AND FUNCTION.
RX PubMed=24043310; DOI=10.1128/mcb.00087-13;
RA Laurent G., de Boer V.C., Finley L.W., Sweeney M., Lu H., Schug T.T.,
RA Cen Y., Jeong S.M., Li X., Sauve A.A., Haigis M.C.;
RT "SIRT4 represses peroxisome proliferator-activated receptor alpha activity
RT to suppress hepatic fat oxidation.";
RL Mol. Cell. Biol. 33:4552-4561(2013).
RN [22]
RP REPRESSION BY AGING, AND TISSUE SPECIFICITY.
RX PubMed=28167758; DOI=10.1073/pnas.1621425114;
RA Lee D.Y., Lin T.E., Lee C.I., Zhou J., Huang Y.H., Lee P.L., Shih Y.T.,
RA Chien S., Chiu J.J.;
RT "MicroRNA-10a is crucial for endothelial response to different flow
RT patterns via interaction of retinoid acid receptors and histone
RT deacetylases.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:2072-2077(2017).
RN [23] {ECO:0007744|PDB:1K7L}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 192-468 IN COMPLEX WITH SYNTHETIC
RP AGONIST.
RX PubMed=11698662; DOI=10.1073/pnas.241410198;
RA Xu H.E., Lambert M.H., Montana V.G., Plunket K.D., Moore L.B.,
RA Collins J.L., Oplinger J.A., Kliewer S.A., Gampe R.T. Jr., McKee D.D.,
RA Moore J.T., Willson T.M.;
RT "Structural determinants of ligand binding selectivity between the
RT peroxisome proliferator-activated receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:13919-13924(2001).
RN [24] {ECO:0007744|PDB:1I7G}
RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 196-468 IN COMPLEX WITH SYNTHETIC
RP AGONIST.
RX PubMed=11587644; DOI=10.1016/s0969-2126(01)00634-7;
RA Cronet P., Petersen J.F.W., Folmer R., Blomberg N., Sjoeblom K.,
RA Karlsson U., Lindstedt E.-L., Bamberg K.;
RT "Structure of the PPARalpha and -gamma ligand binding domain in complex
RT with AZ 242; ligand selectivity and agonist activation in the PPAR
RT family.";
RL Structure 9:699-706(2001).
RN [25] {ECO:0007744|PDB:1KKQ}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 200-468 IN COMPLEX WITH SYNTHETIC
RP AGONIST.
RX PubMed=11845213; DOI=10.1038/415813a;
RA Xu H.E., Stanley T.B., Montana V.G., Lambert M.H., Shearer B.G., Cobb J.E.,
RA McKee D.D., Galardi C.M., Plunket K.D., Nolte R.T., Parks D.J., Moore J.T.,
RA Kliewer S.A., Willson T.M., Stimmel J.B.;
RT "Structural basis for antagonist-mediated recruitment of nuclear co-
RT repressors by PPARalpha.";
RL Nature 415:813-817(2002).
RN [26] {ECO:0007744|PDB:2NPA}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 199-468 IN COMPLEX WITH SYNTHETIC
RP AGONIST.
RX PubMed=17157019; DOI=10.1016/j.bmcl.2006.11.050;
RA Oon Han H., Kim S.H., Kim K.-H., Hur G.-C., Joo Yim H., Chung H.-K.,
RA Ho Woo S., Dong Koo K., Lee C.-S., Sung Koh J., Kim G.T.;
RT "Design and synthesis of oxime ethers of alpha-acyl-beta-phenylpropanoic
RT acids as PPAR dual agonists.";
RL Bioorg. Med. Chem. Lett. 17:937-941(2007).
RN [27] {ECO:0007744|PDB:2P54}
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 202-468 IN COMPLEX WITH SYNTHETIC
RP AGONIST.
RX PubMed=17243659; DOI=10.1021/jm058056x;
RA Sierra M.L., Beneton V., Boullay A.-B., Boyer T., Brewster A.G., Donche F.,
RA Forest M.-C., Fouchet M.-H., Gellibert F.J., Grillot D.A., Lambert M.H.,
RA Laroze A., Le Grumelec C., Linget J.M., Montana V.G., Nguyen V.-L.,
RA Nicodeme E., Patel V., Penfornis A., Pineau O., Pohin D., Potvain F.,
RA Poulain G., Ruault C.B., Saunders M., Toum J., Xu H.E., Xu R.X.,
RA Pianetti P.M.;
RT "Substituted 2-[(4-aminomethyl)phenoxy]-2-methylpropionic acid PPARalpha
RT agonists. 1. Discovery of a novel series of potent HDLc raising agents.";
RL J. Med. Chem. 50:685-695(2007).
RN [28] {ECO:0007744|PDB:2ZNN}
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 200-468 IN COMPLEX WITH THE
RP SYNTHETIC AGONIST TIPP-703.
RX PubMed=19622862; DOI=10.1107/s0907444909015935;
RA Oyama T., Toyota K., Waku T., Hirakawa Y., Nagasawa N., Kasuga J.I.,
RA Hashimoto Y., Miyachi H., Morikawa K.;
RT "Adaptability and selectivity of human peroxisome proliferator-activated
RT receptor (PPAR) pan agonists revealed from crystal structures.";
RL Acta Crystallogr. D 65:786-795(2009).
RN [29] {ECO:0007744|PDB:3G8I}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 199-468 IN COMPLEX WITH
RP ALEGLITAZAR.
RX PubMed=19349176; DOI=10.1016/j.bmcl.2009.03.036;
RA Benardeau A., Benz J., Binggeli A., Blum D., Boehringer M., Grether U.,
RA Hilpert H., Kuhn B., Maerki H.P., Meyer M., Puentener K., Raab S., Ruf A.,
RA Schlatter D., Mohr P.;
RT "Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for
RT the treatment of type II diabetes.";
RL Bioorg. Med. Chem. Lett. 19:2468-2473(2009).
RN [30] {ECO:0007744|PDB:3ET1}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 199-468 IN COMPLEX WITH
RP INDEGLITAZAR.
RX PubMed=19116277; DOI=10.1073/pnas.0811325106;
RA Artis D.R., Lin J.J., Zhang C., Wang W., Mehra U., Perreault M., Erbe D.,
RA Krupka H.I., England B.P., Arnold J., Plotnikov A.N., Marimuthu A.,
RA Nguyen H., Will S., Signaevsky M., Kral J., Cantwell J., Settachatgull C.,
RA Yan D.S., Fong D., Oh A., Shi S., Womack P., Powell B., Habets G.,
RA West B.L., Zhang K.Y.J., Milburn M.V., Vlasuk G.P., Hirth K.P., Nolop K.,
RA Bollag G., Ibrahim P.N., Tobin J.F.;
RT "Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic
RT agent.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:262-267(2009).
CC -!- FUNCTION: Ligand-activated transcription factor. Key regulator of lipid
CC metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-
CC glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by
CC oleylethanolamide, a naturally occurring lipid that regulates satiety.
CC Receptor for peroxisome proliferators such as hypolipidemic drugs and
CC fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty
CC acids. Functions as transcription activator for the ACOX1 and P450
CC genes. Transactivation activity requires heterodimerization with RXRA
CC and is antagonized by NR2C2. May be required for the propagation of
CC clock information to metabolic pathways regulated by PER2.
CC {ECO:0000269|PubMed:10195690, ECO:0000269|PubMed:24043310,
CC ECO:0000269|PubMed:7629123, ECO:0000269|PubMed:7684926,
CC ECO:0000269|PubMed:9556573}.
CC -!- SUBUNIT: Heterodimer; with RXRA. This heterodimerization is required
CC for DNA binding and transactivation activity. Interacts with NCOA3
CC coactivator. Interacts with CITED2; the interaction stimulates its
CC transcriptional activity. Also interacts with PPARBP in vitro.
CC Interacts with AKAP13, LPIN1, PRDM16 and coactivator NCOA6. Interacts
CC with ASXL1 and ASXL2. Interacts with PER2. Interacts with SIRT1; the
CC interaction seems to be modulated by NAD(+) levels (PubMed:24043310).
CC Interacts with CRY1 and CRY2 (By similarity).
CC {ECO:0000250|UniProtKB:P23204, ECO:0000250|UniProtKB:P37230,
CC ECO:0000269|PubMed:10681503, ECO:0000269|PubMed:11587644,
CC ECO:0000269|PubMed:11698662, ECO:0000269|PubMed:11845213,
CC ECO:0000269|PubMed:17157019, ECO:0000269|PubMed:17243659,
CC ECO:0000269|PubMed:19116277, ECO:0000269|PubMed:19349176,
CC ECO:0000269|PubMed:19622862, ECO:0000269|PubMed:21047783,
CC ECO:0000269|PubMed:24043310, ECO:0000269|PubMed:9238002}.
CC -!- INTERACTION:
CC Q07869; P02768-3: ALB; NbExp=3; IntAct=EBI-78615, EBI-25830928;
CC Q07869; P55212: CASP6; NbExp=3; IntAct=EBI-78615, EBI-718729;
CC Q07869; P45973: CBX5; NbExp=3; IntAct=EBI-78615, EBI-78219;
CC Q07869; P06307: CCK; NbExp=3; IntAct=EBI-78615, EBI-6624398;
CC Q07869; Q3L8U1-3: CHD9; NbExp=2; IntAct=EBI-78615, EBI-960730;
CC Q07869; G5E9A7: DMWD; NbExp=3; IntAct=EBI-78615, EBI-10976677;
CC Q07869; P22607: FGFR3; NbExp=3; IntAct=EBI-78615, EBI-348399;
CC Q07869; P62993: GRB2; NbExp=3; IntAct=EBI-78615, EBI-401755;
CC Q07869; Q14957: GRIN2C; NbExp=3; IntAct=EBI-78615, EBI-8285963;
CC Q07869; P06396: GSN; NbExp=3; IntAct=EBI-78615, EBI-351506;
CC Q07869; P42858: HTT; NbExp=3; IntAct=EBI-78615, EBI-466029;
CC Q07869; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-78615, EBI-1055254;
CC Q07869; P13473-2: LAMP2; NbExp=3; IntAct=EBI-78615, EBI-21591415;
CC Q07869; O75376: NCOR1; NbExp=3; IntAct=EBI-78615, EBI-347233;
CC Q07869; Q13133: NR1H3; NbExp=5; IntAct=EBI-78615, EBI-781356;
CC Q07869; D3DTS7: PMP22; NbExp=3; IntAct=EBI-78615, EBI-25882629;
CC Q07869; P54725: RAD23A; NbExp=3; IntAct=EBI-78615, EBI-746453;
CC Q07869; P62826: RAN; NbExp=3; IntAct=EBI-78615, EBI-286642;
CC Q07869; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-78615, EBI-5235340;
CC Q07869; P37173: TGFBR2; NbExp=3; IntAct=EBI-78615, EBI-296151;
CC Q07869; P55072: VCP; NbExp=3; IntAct=EBI-78615, EBI-355164;
CC Q07869-1; P55055-1: NR1H2; NbExp=2; IntAct=EBI-21458428, EBI-21458417;
CC Q07869-1; Q13133: NR1H3; NbExp=2; IntAct=EBI-21458428, EBI-781356;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q07869-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q07869-2; Sequence=VSP_047571, VSP_047572;
CC -!- TISSUE SPECIFICITY: Skeletal muscle, liver, heart and kidney. Expressed
CC in monocytes (PubMed:28167758). {ECO:0000269|PubMed:28167758,
CC ECO:0000269|PubMed:7981125, ECO:0000269|PubMed:8993548}.
CC -!- INDUCTION: Down-regulated by aging. {ECO:0000269|PubMed:28167758}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Peroxisome proliferator-activated
CC receptor entry;
CC URL="https://en.wikipedia.org/wiki/Peroxisome_proliferator-activated_receptor";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ppara/";
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DR EMBL; L02932; AAA36468.1; -; mRNA.
DR EMBL; S74349; AAB32649.1; -; mRNA.
DR EMBL; Y07619; CAA68898.1; -; mRNA.
DR EMBL; AB307690; BAH02281.1; -; mRNA.
DR EMBL; EU650667; ACD12656.1; -; mRNA.
DR EMBL; EU395809; ABY73535.1; -; mRNA.
DR EMBL; CR456547; CAG30433.1; -; mRNA.
DR EMBL; AK289821; BAF82510.1; -; mRNA.
DR EMBL; CR457435; CAG33716.1; -; mRNA.
DR EMBL; AY206718; AAO13489.1; -; Genomic_DNA.
DR EMBL; AL049856; CAI22450.1; -; Genomic_DNA.
DR EMBL; AL078611; CAI22450.1; JOINED; Genomic_DNA.
DR EMBL; Z94161; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471138; EAW73402.1; -; Genomic_DNA.
DR CCDS; CCDS33669.1; -. [Q07869-1]
DR PIR; A49289; A49289.
DR PIR; I56603; I56603.
DR RefSeq; NP_001001928.1; NM_001001928.2. [Q07869-1]
DR RefSeq; NP_005027.2; NM_005036.4. [Q07869-1]
DR RefSeq; XP_005261712.1; XM_005261655.3.
DR RefSeq; XP_005261713.1; XM_005261656.3. [Q07869-1]
DR RefSeq; XP_006724332.1; XM_006724269.3.
DR RefSeq; XP_006724333.1; XM_006724270.3. [Q07869-1]
DR RefSeq; XP_011528541.1; XM_011530239.2. [Q07869-1]
DR RefSeq; XP_011528542.1; XM_011530240.2. [Q07869-1]
DR RefSeq; XP_011528543.1; XM_011530241.2. [Q07869-1]
DR RefSeq; XP_011528544.1; XM_011530242.2. [Q07869-1]
DR RefSeq; XP_011528545.1; XM_011530243.2. [Q07869-1]
DR PDB; 1I7G; X-ray; 2.20 A; A=196-468.
DR PDB; 1K7L; X-ray; 2.50 A; A/C/E/G=192-468.
DR PDB; 1KKQ; X-ray; 3.00 A; A/B/C/D=200-468.
DR PDB; 2NPA; X-ray; 2.30 A; A/C=199-468.
DR PDB; 2P54; X-ray; 1.79 A; A=202-468.
DR PDB; 2REW; X-ray; 2.35 A; A=196-468.
DR PDB; 2ZNN; X-ray; 2.01 A; A=200-468.
DR PDB; 3ET1; X-ray; 2.50 A; A/B=199-468.
DR PDB; 3FEI; X-ray; 2.40 A; A=202-468.
DR PDB; 3G8I; X-ray; 2.20 A; A=199-468.
DR PDB; 3KDT; X-ray; 2.70 A; A/B=196-468.
DR PDB; 3KDU; X-ray; 2.07 A; A/B=196-468.
DR PDB; 3SP6; X-ray; 2.21 A; A=196-468.
DR PDB; 3VI8; X-ray; 1.75 A; A=200-468.
DR PDB; 4BCR; X-ray; 2.50 A; A/B=195-468.
DR PDB; 4CI4; X-ray; 2.30 A; A=195-468.
DR PDB; 5AZT; X-ray; 3.45 A; A/B=201-468.
DR PDB; 5HYK; X-ray; 1.83 A; A=200-468.
DR PDB; 6KAX; X-ray; 1.23 A; A=200-468.
DR PDB; 6KAY; X-ray; 1.74 A; A=200-468.
DR PDB; 6KAZ; X-ray; 1.48 A; A=200-468.
DR PDB; 6KB0; X-ray; 1.35 A; A=200-468.
DR PDB; 6KB1; X-ray; 1.25 A; A=200-468.
DR PDB; 6KB2; X-ray; 1.95 A; A=200-468.
DR PDB; 6KB3; X-ray; 1.45 A; A=200-468.
DR PDB; 6KB4; X-ray; 1.42 A; A=200-468.
DR PDB; 6KB5; X-ray; 1.95 A; A=200-468.
DR PDB; 6KB6; X-ray; 1.43 A; A=200-468.
DR PDB; 6KB7; X-ray; 2.14 A; A=200-468.
DR PDB; 6KB8; X-ray; 1.47 A; A=200-468.
DR PDB; 6KB9; X-ray; 1.55 A; A=200-468.
DR PDB; 6KBA; X-ray; 1.82 A; A=200-468.
DR PDB; 6KXX; X-ray; 1.95 A; A=200-468.
DR PDB; 6KXY; X-ray; 2.00 A; A=200-468.
DR PDB; 6KYP; X-ray; 2.86 A; A/B=200-468.
DR PDB; 6L36; X-ray; 3.30 A; A/B=200-468.
DR PDB; 6L37; X-ray; 2.91 A; A/B=200-468.
DR PDB; 6L38; X-ray; 2.76 A; A/B=200-468.
DR PDB; 6L96; X-ray; 3.20 A; A/B=194-468.
DR PDB; 6LX4; X-ray; 2.13 A; A/B=200-468.
DR PDB; 6LX5; X-ray; 1.87 A; A/B=200-468.
DR PDB; 6LX6; X-ray; 1.30 A; A=200-468.
DR PDB; 6LX7; X-ray; 1.41 A; A=200-468.
DR PDB; 6LX8; X-ray; 1.54 A; A=200-468.
DR PDB; 6LX9; X-ray; 1.40 A; A=200-468.
DR PDB; 6LXA; X-ray; 1.23 A; A=200-468.
DR PDB; 6LXB; X-ray; 2.36 A; A=200-468.
DR PDB; 6LXC; X-ray; 2.03 A; A=200-468.
DR PDB; 7BPY; X-ray; 2.09 A; A/C=200-468.
DR PDB; 7BPZ; X-ray; 2.43 A; A/C=200-468.
DR PDB; 7BQ0; X-ray; 1.77 A; A/C=200-468.
DR PDB; 7BQ1; X-ray; 1.52 A; A=200-468.
DR PDB; 7BQ2; X-ray; 1.52 A; A=200-468.
DR PDB; 7BQ3; X-ray; 1.98 A; A=200-468.
DR PDB; 7BQ4; X-ray; 1.62 A; A=200-468.
DR PDB; 7C6Q; X-ray; 2.76 A; A=196-468.
DR PDB; 7E5F; X-ray; 1.79 A; A=200-468.
DR PDB; 7E5G; X-ray; 1.66 A; A=200-468.
DR PDB; 7E5H; X-ray; 1.66 A; A=200-468.
DR PDB; 7E5I; X-ray; 1.58 A; A=200-468.
DR PDBsum; 1I7G; -.
DR PDBsum; 1K7L; -.
DR PDBsum; 1KKQ; -.
DR PDBsum; 2NPA; -.
DR PDBsum; 2P54; -.
DR PDBsum; 2REW; -.
DR PDBsum; 2ZNN; -.
DR PDBsum; 3ET1; -.
DR PDBsum; 3FEI; -.
DR PDBsum; 3G8I; -.
DR PDBsum; 3KDT; -.
DR PDBsum; 3KDU; -.
DR PDBsum; 3SP6; -.
DR PDBsum; 3VI8; -.
DR PDBsum; 4BCR; -.
DR PDBsum; 4CI4; -.
DR PDBsum; 5AZT; -.
DR PDBsum; 5HYK; -.
DR PDBsum; 6KAX; -.
DR PDBsum; 6KAY; -.
DR PDBsum; 6KAZ; -.
DR PDBsum; 6KB0; -.
DR PDBsum; 6KB1; -.
DR PDBsum; 6KB2; -.
DR PDBsum; 6KB3; -.
DR PDBsum; 6KB4; -.
DR PDBsum; 6KB5; -.
DR PDBsum; 6KB6; -.
DR PDBsum; 6KB7; -.
DR PDBsum; 6KB8; -.
DR PDBsum; 6KB9; -.
DR PDBsum; 6KBA; -.
DR PDBsum; 6KXX; -.
DR PDBsum; 6KXY; -.
DR PDBsum; 6KYP; -.
DR PDBsum; 6L36; -.
DR PDBsum; 6L37; -.
DR PDBsum; 6L38; -.
DR PDBsum; 6L96; -.
DR PDBsum; 6LX4; -.
DR PDBsum; 6LX5; -.
DR PDBsum; 6LX6; -.
DR PDBsum; 6LX7; -.
DR PDBsum; 6LX8; -.
DR PDBsum; 6LX9; -.
DR PDBsum; 6LXA; -.
DR PDBsum; 6LXB; -.
DR PDBsum; 6LXC; -.
DR PDBsum; 7BPY; -.
DR PDBsum; 7BPZ; -.
DR PDBsum; 7BQ0; -.
DR PDBsum; 7BQ1; -.
DR PDBsum; 7BQ2; -.
DR PDBsum; 7BQ3; -.
DR PDBsum; 7BQ4; -.
DR PDBsum; 7C6Q; -.
DR PDBsum; 7E5F; -.
DR PDBsum; 7E5G; -.
DR PDBsum; 7E5H; -.
DR PDBsum; 7E5I; -.
DR AlphaFoldDB; Q07869; -.
DR SMR; Q07869; -.
DR BioGRID; 111461; 81.
DR DIP; DIP-241N; -.
DR IntAct; Q07869; 38.
DR MINT; Q07869; -.
DR STRING; 9606.ENSP00000385523; -.
DR BindingDB; Q07869; -.
DR ChEMBL; CHEMBL239; -.
DR DrugBank; DB08915; Aleglitazar.
DR DrugBank; DB00132; alpha-Linolenic acid.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB04557; Arachidonic Acid.
DR DrugBank; DB01393; Bezafibrate.
DR DrugBank; DB04519; Caprylic acid.
DR DrugBank; DB05416; Cardarine.
DR DrugBank; DB09064; Ciprofibrate.
DR DrugBank; DB09006; Clinofibrate.
DR DrugBank; DB00636; Clofibrate.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB03756; Doconexent.
DR DrugBank; DB05187; Elafibranor.
DR DrugBank; DB06521; Ertiprotafib.
DR DrugBank; DB01039; Fenofibrate.
DR DrugBank; DB13873; Fenofibric acid.
DR DrugBank; DB00573; Fenoprofen.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB02266; Flufenamic acid.
DR DrugBank; DB01241; Gemfibrozil.
DR DrugBank; DB07215; GW-590735.
DR DrugBank; DB01050; Ibuprofen.
DR DrugBank; DB00159; Icosapent.
DR DrugBank; DB07724; Indeglitazar.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB12007; Isoflavone.
DR DrugBank; DB03017; Lauric acid.
DR DrugBank; DB12961; Leukotriene B4.
DR DrugBank; DB06510; Muraglitazar.
DR DrugBank; DB08231; Myristic acid.
DR DrugBank; DB11605; Myrrh.
DR DrugBank; DB01890; N,N-Bis(3-(D-gluconamido)propyl)deoxycholamide.
DR DrugBank; DB04224; Oleic Acid.
DR DrugBank; DB11133; Omega-3 fatty acids.
DR DrugBank; DB03796; Palmitic Acid.
DR DrugBank; DB02746; Phthalic Acid.
DR DrugBank; DB01708; Prasterone.
DR DrugBank; DB06533; Ragaglitazar.
DR DrugBank; DB04971; Reglitazar.
DR DrugBank; DB02709; Resveratrol.
DR DrugBank; DB00412; Rosiglitazone.
DR DrugBank; DB09422; Soybean oil.
DR DrugBank; DB03193; Stearic acid.
DR DrugBank; DB06536; Tesaglitazar.
DR DrugBank; DB00197; Troglitazone.
DR DrugBank; DB00313; Valproic acid.
DR DrugCentral; Q07869; -.
DR GuidetoPHARMACOLOGY; 593; -.
DR SwissLipids; SLP:000001644; -.
DR TCDB; 9.B.208.1.6; the vitamin d3 receptor (vdr) family.
DR iPTMnet; Q07869; -.
DR PhosphoSitePlus; Q07869; -.
DR BioMuta; PPARA; -.
DR DMDM; 3041727; -.
DR MassIVE; Q07869; -.
DR PaxDb; Q07869; -.
DR PeptideAtlas; Q07869; -.
DR PRIDE; Q07869; -.
DR Antibodypedia; 13823; 811 antibodies from 39 providers.
DR DNASU; 5465; -.
DR Ensembl; ENST00000402126.1; ENSP00000385246.1; ENSG00000186951.17. [Q07869-1]
DR Ensembl; ENST00000407236.6; ENSP00000385523.1; ENSG00000186951.17. [Q07869-1]
DR GeneID; 5465; -.
DR KEGG; hsa:5465; -.
DR MANE-Select; ENST00000407236.6; ENSP00000385523.1; NM_005036.6; NP_005027.2.
DR UCSC; uc003bgx.1; human. [Q07869-1]
DR CTD; 5465; -.
DR DisGeNET; 5465; -.
DR GeneCards; PPARA; -.
DR HGNC; HGNC:9232; PPARA.
DR HPA; ENSG00000186951; Tissue enhanced (tongue).
DR MIM; 170998; gene+phenotype.
DR neXtProt; NX_Q07869; -.
DR OpenTargets; ENSG00000186951; -.
DR PharmGKB; PA280; -.
DR VEuPathDB; HostDB:ENSG00000186951; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000157097; -.
DR HOGENOM; CLU_007368_4_1_1; -.
DR InParanoid; Q07869; -.
DR OMA; EMGSIQE; -.
DR PhylomeDB; Q07869; -.
DR TreeFam; TF316304; -.
DR PathwayCommons; Q07869; -.
DR Reactome; R-HSA-1368082; RORA activates gene expression.
DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP).
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-HSA-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR Reactome; R-HSA-9707616; Heme signaling.
DR SignaLink; Q07869; -.
DR SIGNOR; Q07869; -.
DR BioGRID-ORCS; 5465; 13 hits in 1104 CRISPR screens.
DR ChiTaRS; PPARA; human.
DR EvolutionaryTrace; Q07869; -.
DR GeneWiki; Peroxisome_proliferator-activated_receptor_alpha; -.
DR GenomeRNAi; 5465; -.
DR Pharos; Q07869; Tclin.
DR PRO; PR:Q07869; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q07869; protein.
DR Bgee; ENSG00000186951; Expressed in renal medulla and 179 other tissues.
DR ExpressionAtlas; Q07869; baseline and differential.
DR Genevisible; Q07869; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0008289; F:lipid binding; IDA:UniProtKB.
DR GO; GO:0097371; F:MDM2/MDM4 family protein binding; IEA:Ensembl.
DR GO; GO:0051525; F:NFAT protein binding; IEA:Ensembl.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:UniProtKB.
DR GO; GO:0003707; F:nuclear steroid receptor activity; IDA:BHF-UCL.
DR GO; GO:0019902; F:phosphatase binding; IEA:Ensembl.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:BHF-UCL.
DR GO; GO:0001223; F:transcription coactivator binding; IEA:Ensembl.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IPI:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0035095; P:behavioral response to nicotine; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0009267; P:cellular response to starvation; ISS:ARUK-UCL.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0070166; P:enamel mineralization; IEA:Ensembl.
DR GO; GO:0008544; P:epidermis development; IEA:Ensembl.
DR GO; GO:0006631; P:fatty acid metabolic process; IBA:GO_Central.
DR GO; GO:0006094; P:gluconeogenesis; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0010876; P:lipid localization; IEA:Ensembl.
DR GO; GO:0042157; P:lipoprotein metabolic process; IEA:Ensembl.
DR GO; GO:0032099; P:negative regulation of appetite; ISS:UniProtKB.
DR GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0061052; P:negative regulation of cell growth involved in cardiac muscle cell development; IEA:Ensembl.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; IDA:BHF-UCL.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IMP:ARUK-UCL.
DR GO; GO:0045820; P:negative regulation of glycolytic process; IDA:BHF-UCL.
DR GO; GO:1903944; P:negative regulation of hepatocyte apoptotic process; IMP:ARUK-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:BHF-UCL.
DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; IDA:BHF-UCL.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; IDA:BHF-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
DR GO; GO:0032091; P:negative regulation of protein binding; IEA:Ensembl.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:ARUK-UCL.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IMP:ARUK-UCL.
DR GO; GO:0010891; P:negative regulation of sequestering of triglyceride; IDA:BHF-UCL.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:ARUK-UCL.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IMP:ARUK-UCL.
DR GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; TAS:UniProtKB.
DR GO; GO:0045923; P:positive regulation of fatty acid metabolic process; IBA:GO_Central.
DR GO; GO:0046321; P:positive regulation of fatty acid oxidation; ISS:BHF-UCL.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IEA:Ensembl.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IMP:ARUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:ARUK-UCL.
DR GO; GO:0010565; P:regulation of cellular ketone metabolic process; IDA:BHF-UCL.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IDA:BHF-UCL.
DR GO; GO:2000191; P:regulation of fatty acid transport; TAS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IBA:GO_Central.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0033993; P:response to lipid; IBA:GO_Central.
DR GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR IDEAL; IID00382; -.
DR InterPro; IPR003074; 1Cnucl_rcpt.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR003076; PPAR-alpha.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR01288; PROXISOMEPAR.
DR PRINTS; PR01289; PROXISOMPAAR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Biological rhythms;
KW DNA-binding; Lipid-binding; Metal-binding; Nucleus; Receptor;
KW Reference proteome; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..468
FT /note="Peroxisome proliferator-activated receptor alpha"
FT /id="PRO_0000053481"
FT DOMAIN 239..466
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 99..173
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 102..122
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 139..161
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 304..433
FT /note="Required for heterodimerization with RXRA"
FT BINDING 280
FT /ligand="indeglitazar"
FT /ligand_id="ChEBI:CHEBI:188156"
FT /ligand_note="agonist"
FT /evidence="ECO:0000269|PubMed:19116277,
FT ECO:0007744|PDB:3ET1"
FT BINDING 314
FT /ligand="indeglitazar"
FT /ligand_id="ChEBI:CHEBI:188156"
FT /ligand_note="agonist"
FT /evidence="ECO:0000269|PubMed:19116277,
FT ECO:0007744|PDB:3ET1"
FT BINDING 464
FT /ligand="indeglitazar"
FT /ligand_id="ChEBI:CHEBI:188156"
FT /ligand_note="agonist"
FT /evidence="ECO:0000269|PubMed:19116277,
FT ECO:0007744|PDB:3ET1"
FT SITE 433
FT /note="Essential for heterodimerization with RXRA"
FT VAR_SEQ 171..174
FT /note="IRFG -> FCHT (in isoform 2)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_047571"
FT VAR_SEQ 175..468
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_047572"
FT VARIANT 127
FT /note="R -> Q (in dbSNP:rs1800204)"
FT /id="VAR_016110"
FT VARIANT 162
FT /note="L -> V (in dbSNP:rs1800206)"
FT /evidence="ECO:0000269|Ref.10"
FT /id="VAR_016111"
FT VARIANT 227
FT /note="V -> A (in dbSNP:rs1800234)"
FT /id="VAR_016112"
FT VARIANT 268
FT /note="A -> V (in dbSNP:rs1042311)"
FT /evidence="ECO:0000269|PubMed:7684926"
FT /id="VAR_016113"
FT VARIANT 304
FT /note="D -> N (in dbSNP:rs1800242)"
FT /id="VAR_016114"
FT VARIANT 395
FT /note="G -> R (in dbSNP:rs2229245)"
FT /id="VAR_050578"
FT VARIANT 409
FT /note="R -> T (in dbSNP:rs1800243)"
FT /id="VAR_016115"
FT MUTAGEN 122
FT /note="C->G: Prevents DNA binding but no effect on
FT heterodimerization with RXRA."
FT /evidence="ECO:0000269|PubMed:7629123"
FT MUTAGEN 304
FT /note="D->A: Reduced heterodimerization with RXRA. Reduced
FT DNA binding."
FT /evidence="ECO:0000269|PubMed:10195690"
FT MUTAGEN 370
FT /note="L->R: Abolishes heterodimerization with RXRA. No DNA
FT binding."
FT /evidence="ECO:0000269|PubMed:10195690"
FT MUTAGEN 391
FT /note="L->R: Abolishes heterodimerization with RXRA. No DNA
FT binding."
FT /evidence="ECO:0000269|PubMed:10195690"
FT MUTAGEN 422
FT /note="L->R: No effect on heterodimerization with RXRA nor
FT on DNA binding and transactivation activity."
FT /evidence="ECO:0000269|PubMed:7629123"
FT MUTAGEN 431
FT /note="A->T: No effect on heterodimerization with RXRA nor
FT on DNA binding."
FT /evidence="ECO:0000269|PubMed:10195690"
FT MUTAGEN 433
FT /note="L->R: Abolishes heterodimerization with RXRA, DNA
FT binding and transactivation activity."
FT /evidence="ECO:0000269|PubMed:7629123"
FT CONFLICT 71
FT /note="T -> M (in Ref. 3; CAA68898)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="K -> M (in Ref. 3; CAA68898)"
FT /evidence="ECO:0000305"
FT CONFLICT 296
FT /note="G -> A (in Ref. 1; AAA36468)"
FT /evidence="ECO:0000305"
FT CONFLICT 444
FT /note="V -> A (in Ref. 3; CAA68898)"
FT /evidence="ECO:0000305"
FT HELIX 201..217
FT /evidence="ECO:0007829|PDB:6KAX"
FT HELIX 222..230
FT /evidence="ECO:0007829|PDB:6KAX"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:1K7L"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:6KAX"
FT HELIX 244..254
FT /evidence="ECO:0007829|PDB:6KAX"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:6KAX"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:6KAX"
FT HELIX 268..291
FT /evidence="ECO:0007829|PDB:6KAX"
FT TURN 295..299
FT /evidence="ECO:0007829|PDB:6KAX"
FT HELIX 302..321
FT /evidence="ECO:0007829|PDB:6KAX"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:6KAX"
FT STRAND 329..332
FT /evidence="ECO:0007829|PDB:6KAX"
FT TURN 333..336
FT /evidence="ECO:0007829|PDB:6KAX"
FT STRAND 337..340
FT /evidence="ECO:0007829|PDB:6KAX"
FT HELIX 341..346
FT /evidence="ECO:0007829|PDB:6KAX"
FT TURN 348..350
FT /evidence="ECO:0007829|PDB:1KKQ"
FT HELIX 351..353
FT /evidence="ECO:0007829|PDB:6KAX"
FT HELIX 356..367
FT /evidence="ECO:0007829|PDB:6KAX"
FT HELIX 372..383
FT /evidence="ECO:0007829|PDB:6KAX"
FT STRAND 388..390
FT /evidence="ECO:0007829|PDB:6KYP"
FT HELIX 394..415
FT /evidence="ECO:0007829|PDB:6KAX"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:6KYP"
FT HELIX 422..450
FT /evidence="ECO:0007829|PDB:6KAX"
FT STRAND 453..456
FT /evidence="ECO:0007829|PDB:1KKQ"
FT HELIX 458..464
FT /evidence="ECO:0007829|PDB:6KAX"
FT TURN 465..467
FT /evidence="ECO:0007829|PDB:6KB3"
SQ SEQUENCE 468 AA; 52225 MW; 850846FD51ADA883 CRC64;
MVDTESPLCP LSPLEAGDLE SPLSEEFLQE MGNIQEISQS IGEDSSGSFG FTEYQYLGSC
PGSDGSVITD TLSPASSPSS VTYPVVPGSV DESPSGALNI ECRICGDKAS GYHYGVHACE
GCKGFFRRTI RLKLVYDKCD RSCKIQKKNR NKCQYCRFHK CLSVGMSHNA IRFGRMPRSE
KAKLKAEILT CEHDIEDSET ADLKSLAKRI YEAYLKNFNM NKVKARVILS GKASNNPPFV
IHDMETLCMA EKTLVAKLVA NGIQNKEAEV RIFHCCQCTS VETVTELTEF AKAIPGFANL
DLNDQVTLLK YGVYEAIFAM LSSVMNKDGM LVAYGNGFIT REFLKSLRKP FCDIMEPKFD
FAMKFNALEL DDSDISLFVA AIICCGDRPG LLNVGHIEKM QEGIVHVLRL HLQSNHPDDI
FLFPKLLQKM ADLRQLVTEH AQLVQIIKKT ESDAALHPLL QEIYRDMY
