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Peroxisome proliferator-activated receptor alpha (PPAR-alpha) (Nuclear receptor subfamily 1 group C member 1)

 PPARA_RAT               Reviewed;         468 AA.
P37230;
01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
01-OCT-1994, sequence version 1.
22-NOV-2017, entry version 167.
RecName: Full=Peroxisome proliferator-activated receptor alpha;
Short=PPAR-alpha;
AltName: Full=Nuclear receptor subfamily 1 group C member 1;
Name=Ppara; Synonyms=Nr1c1, Ppar;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=1316614; DOI=10.1073/pnas.89.10.4653;
Goettlicher M., Widmark E., Li Q., Gustafsson J.-A.;
"Fatty acids activate a chimera of the clofibric acid-activated
receptor and the glucocorticoid receptor.";
Proc. Natl. Acad. Sci. U.S.A. 89:4653-4657(1992).
[2]
PHOSPHORYLATION.
PubMed=8828512; DOI=10.1210/endo.137.10.8828512;
Shalev A., Siegrist-Kaiser C.A., Yen P.M., Wahli W., Burger A.G.,
Chin W.W., Meier C.A.;
"The peroxisome proliferator-activated receptor alpha is a
phosphoprotein: regulation by insulin.";
Endocrinology 137:4499-4502(1996).
[3]
INTERACTION WITH CITED2.
PubMed=15051727; DOI=10.1074/jbc.M401489200;
Tien E.S., Davis J.W., Vanden Heuvel J.P.;
"Identification of the CREB-binding protein/p300-interacting protein
CITED2 as a peroxisome proliferator-activated receptor alpha
coregulator.";
J. Biol. Chem. 279:24053-24063(2004).
-!- 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. 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.
May be required for the propagation of clock information to
metabolic pathways regulated by PER2 (By similarity).
{ECO:0000250}.
-!- SUBUNIT: Heterodimer; with RXRA. This heterodimerization is
required for DNA binding and transactivation activity. Interacts
with NCOA3 coactivator (By similarity). Interacts with CITED2; the
interaction stimulates its transcriptional activity
(PubMed:15051727). Also interacts with PPARBP in vitro. Interacts
with AKAP13, LPIN1, PRDM16 and coactivator NCOA6. Interacts with
ASXL1 and ASXL2. Interacts with PER2. Interacts with SIRT1; the
interaction seems to be modulated by NAD(+) levels (By
similarity). {ECO:0000250|UniProtKB:P23204,
ECO:0000250|UniProtKB:Q07869, ECO:0000269|PubMed:15051727}.
-!- INTERACTION:
P62161:Calm3; NbExp=2; IntAct=EBI-15674997, EBI-397530;
-!- SUBCELLULAR LOCATION: Nucleus.
-!- TISSUE SPECIFICITY: Expressed predominantly in liver and kidney.
-!- PTM: Phosphorylated. {ECO:0000269|PubMed:8828512}.
-!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
subfamily. {ECO:0000305}.
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EMBL; M88592; AAA41918.1; -; mRNA.
PIR; A45288; A45288.
RefSeq; NP_037328.1; NM_013196.1.
RefSeq; XP_006242218.1; XM_006242156.2.
RefSeq; XP_017450169.1; XM_017594680.1.
RefSeq; XP_017450170.1; XM_017594681.1.
UniGene; Rn.9753; -.
ProteinModelPortal; P37230; -.
SMR; P37230; -.
BioGrid; 247775; 5.
CORUM; P37230; -.
DIP; DIP-29529N; -.
IntAct; P37230; 1.
STRING; 10116.ENSRNOP00000038651; -.
BindingDB; P37230; -.
ChEMBL; CHEMBL2129; -.
iPTMnet; P37230; -.
PhosphoSitePlus; P37230; -.
PaxDb; P37230; -.
PRIDE; P37230; -.
Ensembl; ENSRNOT00000030082; ENSRNOP00000038651; ENSRNOG00000021463.
Ensembl; ENSRNOT00000078928; ENSRNOP00000074329; ENSRNOG00000021463.
GeneID; 25747; -.
KEGG; rno:25747; -.
CTD; 5465; -.
RGD; 3369; Ppara.
eggNOG; KOG3575; Eukaryota.
eggNOG; ENOG410XRZC; LUCA.
GeneTree; ENSGT00870000136388; -.
HOGENOM; HOG000261626; -.
HOVERGEN; HBG106004; -.
InParanoid; P37230; -.
KO; K07294; -.
OMA; FSFTEYQ; -.
PhylomeDB; P37230; -.
TreeFam; TF316304; -.
Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
Reactome; R-RNO-400206; Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha).
PRO; PR:P37230; -.
Proteomes; UP000002494; Chromosome 7.
Bgee; ENSRNOG00000021463; -.
Genevisible; P37230; RN.
GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
GO; GO:0005634; C:nucleus; IDA:RGD.
GO; GO:0003677; F:DNA binding; ISO:RGD.
GO; GO:0008144; F:drug binding; ISS:UniProtKB.
GO; GO:0008289; F:lipid binding; ISS:UniProtKB.
GO; GO:0097371; F:MDM2/MDM4 family protein binding; IPI:RGD.
GO; GO:0051525; F:NFAT protein binding; IPI:RGD.
GO; GO:0004879; F:nuclear receptor activity; IMP:RGD.
GO; GO:0019902; F:phosphatase binding; IPI:RGD.
GO; GO:0032403; F:protein complex binding; IMP:RGD.
GO; GO:0019904; F:protein domain specific binding; IDA:RGD.
GO; GO:0004872; F:receptor activity; ISO:RGD.
GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; ISO:RGD.
GO; GO:0001103; F:RNA polymerase II repressing transcription factor binding; ISO:RGD.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
GO; GO:0003707; F:steroid hormone receptor activity; ISO:RGD.
GO; GO:0001223; F:transcription coactivator binding; IPI:RGD.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; ISO:RGD.
GO; GO:0008134; F:transcription factor binding; ISO:RGD.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; ISO:RGD.
GO; GO:0001190; F:transcriptional activator activity, RNA polymerase II transcription factor binding; ISO:RGD.
GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; ISO:RGD.
GO; GO:0031624; F:ubiquitin conjugating enzyme binding; ISO:RGD.
GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
GO; GO:0035095; P:behavioral response to nicotine; IDA:RGD.
GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
GO; GO:0070166; P:enamel mineralization; ISO:RGD.
GO; GO:0008544; P:epidermis development; ISO:RGD.
GO; GO:0006631; P:fatty acid metabolic process; IMP:RGD.
GO; GO:0007507; P:heart development; IEP:RGD.
GO; GO:0042157; P:lipoprotein metabolic process; IMP:RGD.
GO; GO:0032099; P:negative regulation of appetite; ISS:UniProtKB.
GO; GO:0045776; P:negative regulation of blood pressure; IMP:RGD.
GO; GO:0010887; P:negative regulation of cholesterol storage; ISO:RGD.
GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; ISO:RGD.
GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; ISO:RGD.
GO; GO:1901215; P:negative regulation of neuron death; IDA:RGD.
GO; GO:1902894; P:negative regulation of pri-miRNA transcription from RNA polymerase II promoter; ISO:RGD.
GO; GO:0032091; P:negative regulation of protein binding; IMP:RGD.
GO; GO:0010871; P:negative regulation of receptor biosynthetic process; ISO:RGD.
GO; GO:0010891; P:negative regulation of sequestering of triglyceride; ISO:RGD.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISO:RGD.
GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; IMP:RGD.
GO; GO:0046321; P:positive regulation of fatty acid oxidation; ISO:RGD.
GO; GO:0045722; P:positive regulation of gluconeogenesis; ISO:RGD.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISO:RGD.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
GO; GO:0072366; P:regulation of cellular ketone metabolic process by positive regulation of transcription from RNA polymerase II promoter; ISO:RGD.
GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
GO; GO:0019217; P:regulation of fatty acid metabolic process; ISO:RGD.
GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
GO; GO:0072363; P:regulation of glycolytic process by positive regulation of transcription from RNA polymerase II promoter; ISO:RGD.
GO; GO:0072369; P:regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter; ISO:RGD.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:RGD.
GO; GO:0001666; P:response to hypoxia; IDA:HGNC.
GO; GO:0032868; P:response to insulin; IMP:RGD.
GO; GO:0042060; P:wound healing; ISO:RGD.
Gene3D; 1.10.565.10; -; 1.
Gene3D; 3.30.50.10; -; 1.
InterPro; IPR003074; 1Cnucl_rcpt.
InterPro; IPR003076; 1Cnucl_rcpt_A.
InterPro; IPR035500; NHR_like_dom_sf.
InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
InterPro; IPR001723; Nuclear_hrmn_rcpt.
InterPro; IPR001628; Znf_hrmn_rcpt.
InterPro; IPR013088; Znf_NHR/GATA.
Pfam; PF00104; Hormone_recep; 1.
Pfam; PF00105; zf-C4; 1.
PRINTS; PR01288; PROXISOMEPAR.
PRINTS; PR01289; PROXISOMPAAR.
PRINTS; PR00398; STRDHORMONER.
PRINTS; PR00047; STROIDFINGER.
SMART; SM00430; HOLI; 1.
SMART; SM00399; ZnF_C4; 1.
SUPFAM; SSF48508; SSF48508; 1.
PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
1: Evidence at protein level;
Activator; Biological rhythms; Complete proteome; DNA-binding;
Lipid-binding; Metal-binding; Nucleus; Phosphoprotein; Receptor;
Reference proteome; Transcription; Transcription regulation; Zinc;
Zinc-finger.
CHAIN 1 468 Peroxisome proliferator-activated
receptor alpha.
/FTId=PRO_0000053484.
DNA_BIND 99 173 Nuclear receptor. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
ZN_FING 102 122 NR C4-type. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
ZN_FING 139 161 NR C4-type. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
REGION 280 468 Ligand-binding. {ECO:0000250}.
REGION 304 433 Required for heterodimerization with
RXRA. {ECO:0000250}.
SITE 433 433 Essential for heterodimerization with
RXRA. {ECO:0000250}.
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


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