ID   PPARA_RAT               Reviewed;         468 AA.
AC   P37230;
DT   01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1994, sequence version 1.
DT   27-MAR-2024, entry version 205.
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1316614; DOI=10.1073/pnas.89.10.4653;
RA   Goettlicher M., Widmark E., Li Q., Gustafsson J.-A.;
RT   "Fatty acids activate a chimera of the clofibric acid-activated receptor
RT   and the glucocorticoid receptor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:4653-4657(1992).
RN   [2]
RP   PHOSPHORYLATION.
RX   PubMed=8828512; DOI=10.1210/endo.137.10.8828512;
RA   Shalev A., Siegrist-Kaiser C.A., Yen P.M., Wahli W., Burger A.G.,
RA   Chin W.W., Meier C.A.;
RT   "The peroxisome proliferator-activated receptor alpha is a phosphoprotein:
RT   regulation by insulin.";
RL   Endocrinology 137:4499-4502(1996).
RN   [3]
RP   INTERACTION WITH CITED2.
RX   PubMed=15051727; DOI=10.1074/jbc.m401489200;
RA   Tien E.S., Davis J.W., Vanden Heuvel J.P.;
RT   "Identification of the CREB-binding protein/p300-interacting protein CITED2
RT   as a peroxisome proliferator-activated receptor alpha coregulator.";
RL   J. Biol. Chem. 279:24053-24063(2004).
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 a 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 (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Heterodimer; with RXRA. This heterodimerization is required
CC       for DNA binding and transactivation activity. Interacts with NCOA3
CC       coactivator (By similarity). Interacts with CITED2; the interaction
CC       stimulates its transcriptional activity (PubMed:15051727). Also
CC       interacts with PPARBP in vitro. Interacts with AKAP13, LPIN1, PRDM16
CC       and coactivator NCOA6. Interacts with ASXL1 and ASXL2. Interacts with
CC       PER2. Interacts with SIRT1; the interaction seems to be modulated by
CC       NAD(+) levels (By similarity). Interacts with CRY1 and CRY2 (By
CC       similarity). {ECO:0000250|UniProtKB:P23204,
CC       ECO:0000250|UniProtKB:Q07869, ECO:0000269|PubMed:15051727}.
CC   -!- INTERACTION:
CC       P37230; P62161: Calm3; NbExp=2; IntAct=EBI-15674997, EBI-397530;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in liver and kidney.
CC   -!- PTM: Phosphorylated. {ECO:0000269|PubMed:8828512}.
CC   -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC       subfamily. {ECO:0000305}.
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DR   EMBL; M88592; AAA41918.1; -; mRNA.
DR   PIR; A45288; A45288.
DR   RefSeq; NP_037328.1; NM_013196.1.
DR   RefSeq; XP_006242218.1; XM_006242156.2.
DR   RefSeq; XP_017450169.1; XM_017594680.1.
DR   RefSeq; XP_017450170.1; XM_017594681.1.
DR   AlphaFoldDB; P37230; -.
DR   SMR; P37230; -.
DR   BioGRID; 247775; 5.
DR   CORUM; P37230; -.
DR   DIP; DIP-29529N; -.
DR   IntAct; P37230; 1.
DR   STRING; 10116.ENSRNOP00000038651; -.
DR   BindingDB; P37230; -.
DR   ChEMBL; CHEMBL2129; -.
DR   iPTMnet; P37230; -.
DR   PhosphoSitePlus; P37230; -.
DR   PaxDb; 10116-ENSRNOP00000038651; -.
DR   Ensembl; ENSRNOT00000030082.3; ENSRNOP00000038651.1; ENSRNOG00000021463.3.
DR   Ensembl; ENSRNOT00055055491; ENSRNOP00055045786; ENSRNOG00055032099.
DR   Ensembl; ENSRNOT00060040199; ENSRNOP00060033175; ENSRNOG00060023253.
DR   Ensembl; ENSRNOT00065057129; ENSRNOP00065047023; ENSRNOG00065033228.
DR   GeneID; 25747; -.
DR   KEGG; rno:25747; -.
DR   AGR; RGD:3369; -.
DR   CTD; 5465; -.
DR   RGD; 3369; Ppara.
DR   eggNOG; KOG3575; Eukaryota.
DR   GeneTree; ENSGT00940000157097; -.
DR   HOGENOM; CLU_007368_4_1_1; -.
DR   InParanoid; P37230; -.
DR   OMA; ANNNPPF; -.
DR   OrthoDB; 3475284at2759; -.
DR   PhylomeDB; P37230; -.
DR   TreeFam; TF316304; -.
DR   Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
DR   Reactome; R-RNO-400206; Regulation of lipid metabolism by PPARalpha.
DR   Reactome; R-RNO-4090294; SUMOylation of intracellular receptors.
DR   Reactome; R-RNO-9707564; Cytoprotection by HMOX1.
DR   PRO; PR:P37230; -.
DR   Proteomes; UP000002494; Chromosome 7.
DR   Bgee; ENSRNOG00000021463; Expressed in liver and 18 other cell types or tissues.
DR   GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0001216; F:DNA-binding transcription activator activity; ISO:RGD.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR   GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:RGD.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR   GO; GO:0008289; F:lipid binding; ISS:UniProtKB.
DR   GO; GO:0097371; F:MDM2/MDM4 family protein binding; IPI:RGD.
DR   GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:RGD.
DR   GO; GO:0051525; F:NFAT protein binding; IPI:RGD.
DR   GO; GO:0004879; F:nuclear receptor activity; IMP:RGD.
DR   GO; GO:0003707; F:nuclear steroid receptor activity; ISO:RGD.
DR   GO; GO:0019902; F:phosphatase binding; IPI:RGD.
DR   GO; GO:0019904; F:protein domain specific binding; IDA:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IMP:RGD.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR   GO; GO:0038023; F:signaling receptor activity; ISO:RGD.
DR   GO; GO:0001223; F:transcription coactivator binding; IPI:RGD.
DR   GO; GO:0031624; F:ubiquitin conjugating enzyme binding; ISO:RGD.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0035095; P:behavioral response to nicotine; IDA:RGD.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0071332; P:cellular response to fructose stimulus; IEP:RGD.
DR   GO; GO:0009267; P:cellular response to starvation; ISO:RGD.
DR   GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR   GO; GO:0070166; P:enamel mineralization; ISO:RGD.
DR   GO; GO:0008544; P:epidermis development; ISO:RGD.
DR   GO; GO:0006631; P:fatty acid metabolic process; IMP:RGD.
DR   GO; GO:0006094; P:gluconeogenesis; ISO:RGD.
DR   GO; GO:0007507; P:heart development; IEP:RGD.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0042157; P:lipoprotein metabolic process; IMP:RGD.
DR   GO; GO:0032099; P:negative regulation of appetite; ISS:UniProtKB.
DR   GO; GO:0045776; P:negative regulation of blood pressure; IMP:RGD.
DR   GO; GO:0061052; P:negative regulation of cell growth involved in cardiac muscle cell development; IMP:RGD.
DR   GO; GO:0010887; P:negative regulation of cholesterol storage; ISO:RGD.
DR   GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISO:RGD.
DR   GO; GO:0045820; P:negative regulation of glycolytic process; ISO:RGD.
DR   GO; GO:1903944; P:negative regulation of hepatocyte apoptotic process; ISO:RGD.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR   GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; ISO:RGD.
DR   GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; ISO:RGD.
DR   GO; GO:1902894; P:negative regulation of miRNA transcription; ISO:RGD.
DR   GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR   GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; ISO:RGD.
DR   GO; GO:0010891; P:negative regulation of sequestering of triglyceride; ISO:RGD.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR   GO; GO:0046209; P:nitric oxide metabolic process; IEP:RGD.
DR   GO; GO:2001171; P:positive regulation of ATP biosynthetic process; ISO:RGD.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS: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; ISO:RGD.
DR   GO; GO:0045722; P:positive regulation of gluconeogenesis; ISO:RGD.
DR   GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISO:RGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:1904189; P:positive regulation of transformation of host cell by virus; IEA:Ensembl.
DR   GO; GO:0010565; P:regulation of cellular ketone metabolic process; ISO:RGD.
DR   GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:RGD.
DR   GO; GO:0019217; P:regulation of fatty acid metabolic process; ISO:RGD.
DR   GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR   GO; GO:0010883; P:regulation of lipid storage; IEP:RGD.
DR   GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR   GO; GO:0001666; P:response to hypoxia; IDA:HGNC-UCL.
DR   GO; GO:0032868; P:response to insulin; IMP:RGD.
DR   GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0042060; P:wound healing; ISO:RGD.
DR   CDD; cd06965; NR_DBD_Ppar; 1.
DR   CDD; cd06932; NR_LBD_PPAR; 1.
DR   Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1.
DR   Gene3D; 1.10.565.10; Retinoid X Receptor; 1.
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   PANTHER; PTHR24082; NUCLEAR HORMONE RECEPTOR; 1.
DR   PANTHER; PTHR24082:SF197; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA; 1.
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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR   SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1.
DR   PROSITE; PS51843; NR_LBD; 1.
DR   PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR   PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
DR   Genevisible; P37230; RN.
PE   1: Evidence at protein level;
KW   Activator; Biological rhythms; DNA-binding; Lipid-binding; Metal-binding;
KW   Nucleus; Phosphoprotein; Receptor; Reference proteome; Transcription;
KW   Transcription regulation; Zinc; Zinc-finger.
FT   CHAIN           1..468
FT                   /note="Peroxisome proliferator-activated receptor alpha"
FT                   /id="PRO_0000053484"
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                   /evidence="ECO:0000250"
FT   SITE            433
FT                   /note="Essential for heterodimerization with RXRA"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   468 AA;  52377 MW;  2A89E7D715C8DBA9 CRC64;
     MVDTESPICP LSPLEADDLE SPLSEEFLQE MGNIQEISQS LGEESSGSFS FADYQYLGSC
     PGSEGSVITD TLSPASSPSS VSCPAVPTST DESPGNALNI ECRICGDKAS GYHYGVHACE
     GCKGFFRRTI RLKLAYDKCD RSCKIQKKNR NKCQYCRFHK CLSVGMSHNA IRFGRMPRSE
     KAKLKAEILT CEHDLKDSET ADLKSLAKRI HEAYLKNFNM NKVKARVILA GKTSNNPPFV
     IHDMETLCMA EKTLVAKMVA NGVENKEAEV RFFHCCQCMS VETVTELTEF AKAIPGFANL
     DLNDQVTLLK YGVYEAIFTM LSSLMNKDGM LIAYGNGFIT REFLKNLRKP FCDIMEPKFD
     FAMKFNALEL DDSDISLFVA AIICCGDRPG LLNIGYIEKL QEGIVHVLKL HLQSNHPDDT
     FLFPKLLQKM VDLRQLVTEH AQLVQVIKKT ESDAALHPLL QEIYRDMY
//