ID   PPARD_MOUSE             Reviewed;         440 AA.
AC   P35396; P37239;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   24-JAN-2024, entry version 208.
DE   RecName: Full=Peroxisome proliferator-activated receptor delta;
DE            Short=PPAR-delta;
DE   AltName: Full=Nuclear hormone receptor 1;
DE            Short=NUC1;
DE   AltName: Full=Nuclear receptor subfamily 1 group C member 2;
DE   AltName: Full=Peroxisome proliferator-activated receptor beta;
DE            Short=PPAR-beta;
GN   Name=Ppard; Synonyms=Nr1c2, Pparb;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Adipocyte;
RX   PubMed=7836471; DOI=10.1074/jbc.270.5.2367;
RA   Amri E.-Z., Bonino F., Ailhaud G., Abumrad N.A., Grimaldi P.A.;
RT   "Cloning of a protein that mediates transcriptional effects of fatty acids
RT   in preadipocytes. Homology to peroxisome proliferator-activated
RT   receptors.";
RL   J. Biol. Chem. 270:2367-2371(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RX   PubMed=8041794; DOI=10.1073/pnas.91.15.7355;
RA   Kliewer S.A., Forman B.M., Blumberg B., Ong E.S., Borgmeyer U.,
RA   Mangelsdorf D.J., Umesono K., Evans R.M.;
RT   "Differential expression and activation of a family of murine peroxisome
RT   proliferator-activated receptors.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:7355-7359(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-145.
RC   STRAIN=BALB/cJ; TISSUE=Brain;
RX   PubMed=8240342; DOI=10.1006/bbrc.1993.2302;
RA   Chen F., Law S.W., O'Malley B.W.;
RT   "Identification of two mPPAR related receptors and evidence for the
RT   existence of five subfamily members.";
RL   Biochem. Biophys. Res. Commun. 196:671-677(1993).
RN   [5]
RP   INTERACTION WITH CRY1 AND CRY2.
RX   PubMed=28683290; DOI=10.1016/j.cmet.2017.06.002;
RA   Jordan S.D., Kriebs A., Vaughan M., Duglan D., Fan W., Henriksson E.,
RA   Huber A.L., Papp S.J., Nguyen M., Afetian M., Downes M., Yu R.T.,
RA   Kralli A., Evans R.M., Lamia K.A.;
RT   "CRY1/2 selectively repress PPARdelta and limit exercise capacity.";
RL   Cell Metab. 26:243-255(2017).
RN   [6]
RP   INTERACTION WITH CRY1 AND CRY2.
RX   PubMed=28751364; DOI=10.1073/pnas.1704955114;
RA   Kriebs A., Jordan S.D., Soto E., Henriksson E., Sandate C.R., Vaughan M.E.,
RA   Chan A.B., Duglan D., Papp S.J., Huber A.L., Afetian M.E., Yu R.T.,
RA   Zhao X., Downes M., Evans R.M., Lamia K.A.;
RT   "Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors
RT   and modulate transcriptional activity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 114:8776-8781(2017).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX   PubMed=35675826; DOI=10.1016/j.cmet.2022.05.005;
RA   Zhou N., Qi H., Liu J., Zhang G., Liu J., Liu N., Zhu M., Zhao X., Song C.,
RA   Zhou Z., Gong J., Li R., Bai X., Jin Y., Song Y., Yin Y.;
RT   "Deubiquitinase OTUD3 regulates metabolism homeostasis in response to
RT   nutritional stresses.";
RL   Cell Metab. 34:1023-1041.e8(2022).
CC   -!- FUNCTION: Ligand-activated transcription factor key mediator of energy
CC       metabolism in adipose tissues (PubMed:35675826). Receptor that binds
CC       peroxisome proliferators such as hypolipidemic drugs and fatty acids.
CC       Has a preference for poly-unsaturated fatty acids, such as gamma-
CC       linoleic acid and eicosapentanoic acid. Once activated by a ligand, the
CC       receptor binds to promoter elements of target genes. Regulates the
CC       peroxisomal beta-oxidation pathway of fatty acids. Functions as
CC       transcription activator for the acyl-CoA oxidase gene. Decreases
CC       expression of NPC1L1 once activated by a ligand (By similarity).
CC       {ECO:0000250|UniProtKB:Q03181, ECO:0000269|PubMed:35675826}.
CC   -!- SUBUNIT: Heterodimer with the retinoid X receptor (By similarity).
CC       Interacts (via domain NR LBD) with CRY1 and CRY2 in a ligand-dependent
CC       manner (PubMed:28683290, PubMed:28751364).
CC       {ECO:0000250|UniProtKB:Q03181, ECO:0000269|PubMed:28683290,
CC       ECO:0000269|PubMed:28751364}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:35675826}.
CC   -!- TISSUE SPECIFICITY: Heart, adrenal and intestine.
CC   -!- PTM: 'Lys-48'-linked polyubiquitinated; leading to proteasomal
CC       degradation. Deubiquitinated and stabilized by OTUD3.
CC       {ECO:0000269|PubMed:35675826}.
CC   -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC       subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA03332.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; L28116; AAA63394.1; -; mRNA.
DR   EMBL; U10375; AAA19972.1; -; mRNA.
DR   EMBL; BC070398; AAH70398.1; -; mRNA.
DR   EMBL; U01665; AAA03332.1; ALT_INIT; mRNA.
DR   CCDS; CCDS28575.1; -.
DR   PIR; I55442; I55442.
DR   RefSeq; NP_035275.1; NM_011145.3.
DR   AlphaFoldDB; P35396; -.
DR   SMR; P35396; -.
DR   BioGRID; 202319; 13.
DR   DIP; DIP-29851N; -.
DR   IntAct; P35396; 6.
DR   STRING; 10090.ENSMUSP00000002320; -.
DR   BindingDB; P35396; -.
DR   ChEMBL; CHEMBL2458; -.
DR   SwissLipids; SLP:000000397; -.
DR   PhosphoSitePlus; P35396; -.
DR   EPD; P35396; -.
DR   PaxDb; 10090-ENSMUSP00000002320; -.
DR   ProteomicsDB; 291646; -.
DR   Antibodypedia; 4322; 729 antibodies from 43 providers.
DR   DNASU; 19015; -.
DR   Ensembl; ENSMUST00000002320.16; ENSMUSP00000002320.9; ENSMUSG00000002250.17.
DR   GeneID; 19015; -.
DR   KEGG; mmu:19015; -.
DR   UCSC; uc008bqk.1; mouse.
DR   AGR; MGI:101884; -.
DR   CTD; 5467; -.
DR   MGI; MGI:101884; Ppard.
DR   VEuPathDB; HostDB:ENSMUSG00000002250; -.
DR   eggNOG; KOG3575; Eukaryota.
DR   GeneTree; ENSGT00940000156676; -.
DR   HOGENOM; CLU_007368_4_1_1; -.
DR   InParanoid; P35396; -.
DR   OMA; RPGLMDV; -.
DR   OrthoDB; 3475284at2759; -.
DR   PhylomeDB; P35396; -.
DR   TreeFam; TF316304; -.
DR   Reactome; R-MMU-200425; Carnitine metabolism.
DR   Reactome; R-MMU-204174; Regulation of pyruvate dehydrogenase (PDH) complex.
DR   Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR   Reactome; R-MMU-5362517; Signaling by Retinoic Acid.
DR   BioGRID-ORCS; 19015; 5 hits in 79 CRISPR screens.
DR   ChiTaRS; Ppard; mouse.
DR   PRO; PR:P35396; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; P35396; Protein.
DR   Bgee; ENSMUSG00000002250; Expressed in ectoplacental cone and 174 other cell types or tissues.
DR   ExpressionAtlas; P35396; baseline and differential.
DR   GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI.
DR   GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR   GO; GO:0008047; F:enzyme activator activity; TAS:UniProtKB.
DR   GO; GO:0005504; F:fatty acid binding; ISO:MGI.
DR   GO; GO:0070539; F:linoleic acid binding; ISS:UniProtKB.
DR   GO; GO:0008289; F:lipid binding; ISS:UniProtKB.
DR   GO; GO:0051059; F:NF-kappaB binding; ISO:MGI.
DR   GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR   GO; GO:0016501; F:prostacyclin receptor activity; TAS:UniProtKB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0001223; F:transcription coactivator binding; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0060612; P:adipose tissue development; IMP:MGI.
DR   GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR   GO; GO:0097190; P:apoptotic signaling pathway; ISO:MGI.
DR   GO; GO:0008366; P:axon ensheathment; IMP:MGI.
DR   GO; GO:0030154; P:cell differentiation; IDA:MGI.
DR   GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR   GO; GO:0031589; P:cell-substrate adhesion; IMP:MGI.
DR   GO; GO:0071456; P:cellular response to hypoxia; IGI:MGI.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:MGI.
DR   GO; GO:0031669; P:cellular response to nutrient levels; ISO:MGI.
DR   GO; GO:0007566; P:embryo implantation; IDA:MGI.
DR   GO; GO:0097009; P:energy homeostasis; IMP:BHF-UCL.
DR   GO; GO:0008544; P:epidermis development; TAS:MGI.
DR   GO; GO:0050673; P:epithelial cell proliferation; IGI:MGI.
DR   GO; GO:0070341; P:fat cell proliferation; IMP:MGI.
DR   GO; GO:0006635; P:fatty acid beta-oxidation; IEP:UniProtKB.
DR   GO; GO:0006631; P:fatty acid metabolic process; IBA:GO_Central.
DR   GO; GO:0019395; P:fatty acid oxidation; ISO:MGI.
DR   GO; GO:0015908; P:fatty acid transport; IEP:UniProtKB.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0051546; P:keratinocyte migration; IMP:MGI.
DR   GO; GO:0043616; P:keratinocyte proliferation; IMP:MGI.
DR   GO; GO:0006629; P:lipid metabolic process; IMP:MGI.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR   GO; GO:0010887; P:negative regulation of cholesterol storage; IBA:GO_Central.
DR   GO; GO:0032966; P:negative regulation of collagen biosynthetic process; ISO:MGI.
DR   GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IGI:MGI.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; IBA:GO_Central.
DR   GO; GO:1902894; P:negative regulation of miRNA transcription; IDA:BHF-UCL.
DR   GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:CACAO.
DR   GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:MGI.
DR   GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:MGI.
DR   GO; GO:0008654; P:phospholipid biosynthetic process; ISO:MGI.
DR   GO; GO:0001890; P:placenta development; IMP:MGI.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0045684; P:positive regulation of epidermis development; ISO:MGI.
DR   GO; GO:0070346; P:positive regulation of fat cell proliferation; IMP:MGI.
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:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:CACAO.
DR   GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR   GO; GO:2000288; P:positive regulation of myoblast proliferation; IMP:CACAO.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:MGI.
DR   GO; GO:0043415; P:positive regulation of skeletal muscle tissue regeneration; IMP:CACAO.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0006029; P:proteoglycan metabolic process; ISO:MGI.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI.
DR   GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:MGI.
DR   GO; GO:0045598; P:regulation of fat cell differentiation; IMP:MGI.
DR   GO; GO:0050796; P:regulation of insulin secretion; NAS:UniProtKB.
DR   GO; GO:0014842; P:regulation of skeletal muscle satellite cell proliferation; IMP:CACAO.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:MGI.
DR   GO; GO:0042311; P:vasodilation; ISO:MGI.
DR   GO; GO:0042060; P:wound healing; IMP:MGI.
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; IPR003075; 1Cnucl_rcpt_B.
DR   InterPro; IPR035500; NHR-like_dom_sf.
DR   InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR   InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR   InterPro; IPR001628; Znf_hrmn_rcpt.
DR   InterPro; IPR013088; Znf_NHR/GATA.
DR   PANTHER; PTHR24082; NUCLEAR HORMONE RECEPTOR; 1.
DR   PANTHER; PTHR24082:SF15; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR DELTA; 1.
DR   Pfam; PF00104; Hormone_recep; 1.
DR   Pfam; PF00105; zf-C4; 1.
DR   PRINTS; PR01288; PROXISOMEPAR.
DR   PRINTS; PR01290; PROXISOMPABR.
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; P35396; MM.
PE   1: Evidence at protein level;
KW   Activator; DNA-binding; Metal-binding; Nucleus; Receptor;
KW   Reference proteome; Transcription; Transcription regulation;
KW   Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN           1..440
FT                   /note="Peroxisome proliferator-activated receptor delta"
FT                   /id="PRO_0000053487"
FT   DOMAIN          210..438
FT                   /note="NR LBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT   DNA_BIND        70..144
FT                   /note="Nuclear receptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         73..93
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         110..132
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   REGION          1..53
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..22
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        33..53
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        149..150
FT                   /note="EA -> DG (in Ref. 2; AAA19972)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   440 AA;  49715 MW;  58E0F595DD193FDA CRC64;
     MEQPQEETPE AREEEKEEVA MGDGAPELNG GPEHTLPSSS CADLSQNSSP SSLLDQLQMG
     CDGASGGSLN MECRVCGDKA SGFHYGVHAC EGCKGFFRRT IRMKLEYEKC DRICKIQKKN
     RNKCQYCRFQ KCLALGMSHN AIRFGRMPEA EKRKLVAGLT ASEGCQHNPQ LADLKAFSKH
     IYNAYLKNFN MTKKKARSIL TGKSSHNAPF VIHDIETLWQ AEKGLVWKQL VNGLPPYNEI
     SVHVFYRCQS TTVETVRELT EFAKNIPNFS SLFLNDQVTL LKYGVHEAIF AMLASIVNKD
     GLLVANGSGF VTHEFLRSLR KPFSDIIEPK FEFAVKFNAL ELDDSDLALF IAAIILCGDR
     PGLMNVPQVE AIQDTILRAL EFHLQVNHPD SQYLFPKLLQ KMADLRQLVT EHAQMMQWLK
     KTESETLLHP LLQEIYKDMY
//