Swiss-Prot entry
ID PPAR_HUMAN STANDARD; PRT; 468 AA.
AC Q07869; Q16241; Q92486; Q92689; Q9Y3N1;
DT 01-OCT-1994 (Rel. 30, Created)
DT 15-JUL-1998 (Rel. 36, Last sequence update)
DT 01-MAY-2005 (Rel. 47, Last annotation update)
DE Peroxisome proliferator activated receptor alpha (PPAR-alpha).
GN Name=PPARA; Synonyms=NR1C1, PPAR;
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, AND VARIANT VAL-268.
RC TISSUE=Liver;
RX MEDLINE=93277839; PubMed=7684926 [NCBI, ExPASy, EBI, Israel, Japan];
RA Sher T., Yi H.F., McBride O.W., Gonzales F.J.;
RT "cDNA cloning, chromosomal mapping, and functional characterization of
RT the human peroxisome proliferator activated receptor.";
RL Biochemistry 32:5598-5604(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Liver;
RX MEDLINE=95071923; PubMed=7981125 [NCBI, ExPASy, EBI, Israel, Japan]; 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
RT to PPAR activators.";
RL J. Steroid Biochem. Mol. Biol. 51:157-166(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=97146692; PubMed=8993548 [NCBI, ExPASy, EBI, Israel, Japan];
RA Tugwood J.D., Aldridge T.C., Lambe K.G., Macdonald N., Woodyatt N.J.;
RT "Peroxisome proliferator-activated receptors: structures and
RT function.";
RL Ann. N. Y. Acad. Sci. 804:252-265(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802 [NCBI, ExPASy, EBI, Israel, Japan]; 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:RESEARCH84.1-RESEARCH84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-162.
RA Rieder M.J., Carrington D.P., da Ponte S.H., Hastings N.C.,
RA Ahearn M.O., Kuldanek S.A., Rajkumar N., Toth E.J., Yi Q.,
RA Nickerson D.A.;
RT "SeattleSNPs. NHLBI HL66682 program for genomic applications, UW-
RT FHCRC, Seattle, WA (URL: http://pga.gs.washington.edu).";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX MEDLINE=20057165; PubMed=10591208 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA 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.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA 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.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [7]
RP INTERACTION WITH NCOA3.
RX MEDLINE=97385128; PubMed=9238002 [NCBI, ExPASy, EBI, Israel, Japan]; 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
RT related to SRC-1 and TIF2.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:8479-8484(1997).
RN [8]
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).
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.
CC -!- SUBUNIT: Heterodimer with the retinoid X receptor. Interacts with
CC NCOA3 and NCOA6 coactivators, leading to a strong increase of
CC transcription of target genes (By similarity).
CC -!- INTERACTION:
CC P55345:hrmt1l1; NbExp=1; IntAct=EBI-78615, EBI-78458;
CC -!- SUBCELLULAR LOCATION: Nuclear.
CC -!- TISSUE SPECIFICITY: Skeletal muscle, liver, heart and kidney.
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; L02932; AAA36468.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; S74349; AAB32649.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; Y07619; CAA68898.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; CR456547; CAG30433.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AY206718; AAO13489.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AL049856; CAI22450.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AL078611; CAI22450.1; JOINED. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AL078611; CAI18764.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AL049856; CAI18764.1; JOINED. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR PIR; A49289; A49289.
DR PIR; I56603; I56603.
DR PDB; 1I7G; X-ray; A=182-468. [ExPASy / RCSB]
DR PDB; 1K7L; X-ray; A/C/E/G=181-468. [ExPASy / RCSB]
DR PDB; 1KKQ; X-ray; A/B/C/D=200-468. [ExPASy / RCSB]
DR IntAct; Q07869; -.
DR TRANSFAC; T02726; -.
DR Ensembl; ENSG00000186951; Homo_sapiens
DR Genew; HGNC:9232; PPARA.
DR CleanEx; HGNC:9232; PPARA.
DR MIM; 170998; -. [NCBI / EBI]
DR GeneCards; PPARA.
DR GeneLynx; PPARA.
DR GenAtlas; PPARA.
DR SOURCE; PPARA.
DR GO; GO:0003700; F:transcription factor activity; TAS.
DR GO; GO:0006631; P:fatty acid metabolism; TAS.
DR GO; GO:0006366; P:transcription from Pol II promoter; 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; PR01289; PROXISOMPAAR.
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 SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
DR CMR; Q07869.
DR HOVERGEN [Family / Alignment / Tree]
DR BLOCKS; Q07869.
DR ProtoNet; Q07869.
DR ProtoMap; Q07869.
DR PRESAGE; Q07869.
DR DIP; Q07869.
DR ModBase; Q07869.
DR SWISS-2DPAGE; GET REGION ON 2D PAGE.
KW 3D-structure; Activator; DNA-binding; Multigene family;
KW Nuclear protein; Polymorphism; Receptor; Transcription;
KW Transcription regulation; Zinc-finger.
FT DNA_BIND 99 173 Nuclear receptor-type.
FT ZN_FING 102 122 C4-type.
FT ZN_FING 139 161 C4-type.
FT DOMAIN 281 468 Ligand-binding (Potential).
FT VARIANT 127 127 R -> Q (in dbSNP:1800204).
FT /FTId=VAR_016110.
FT VARIANT 162 162 L -> V (in dbSNP:1800206).
FT /FTId=VAR_016111.
FT VARIANT 227 227 V -> A (in dbSNP:1800234).
FT /FTId=VAR_016112.
FT VARIANT 268 268 A -> V (in dbSNP:1042311).
FT /FTId=VAR_016113.
FT VARIANT 304 304 D -> N (in dbSNP:1800242).
FT /FTId=VAR_016114.
FT VARIANT 409 409 R -> T (in dbSNP:1800243).
FT /FTId=VAR_016115.
FT CONFLICT 71 71 T -> M (in Ref. 3).
FT CONFLICT 123 123 K -> M (in Ref. 3).
FT CONFLICT 296 296 G -> A (in Ref. 1).
FT CONFLICT 444 444 V -> A (in Ref. 3).
FT HELIX 201 217
FT HELIX 222 228
FT STRAND 239 241
FT HELIX 244 251
FT TURN 252 253
FT HELIX 268 292
FT TURN 293 293
FT TURN 295 296
FT TURN 298 299
FT HELIX 302 321
FT HELIX 322 324
FT STRAND 325 326
FT TURN 327 328
FT STRAND 329 332
FT HELIX 333 335
FT TURN 336 336
FT STRAND 337 340
FT HELIX 341 346
FT TURN 349 351
FT HELIX 352 366
FT TURN 367 368
FT HELIX 372 383
FT TURN 389 390
FT HELIX 394 415
FT TURN 417 418
FT TURN 420 421
FT HELIX 422 450
FT TURN 452 453
FT HELIX 458 468
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
//