PPARA_RAT
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 03-AUG-2022, entry version 196.
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 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; P37230; -.
DR Ensembl; ENSRNOT00000030082; ENSRNOP00000038651; ENSRNOG00000021463.
DR GeneID; 25747; -.
DR KEGG; rno:25747; -.
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; EMGSIQE; -.
DR OrthoDB; 1240230at2759; -.
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 tissues.
DR Genevisible; P37230; RN.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA: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; ISO: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: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: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; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEP:RGD.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0010876; P:lipid localization; IEP:RGD.
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:1901215; P:negative regulation of neuron death; IDA:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; IMP:RGD.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; 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:2000272; P:negative regulation of signaling receptor activity; 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:2001171; P:positive regulation of ATP biosynthetic process; ISO:RGD.
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:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; ISO:RGD.
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:0019217; P:regulation of fatty acid metabolic process; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IBA:GO_Central.
DR GO; GO:0010883; P:regulation of lipid storage; IEP:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA: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:0033993; P:response to lipid; IBA:GO_Central.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0042060; P:wound healing; ISO:RGD.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 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 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 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
