PPARG_PIG
ID PPARG_PIG Reviewed; 504 AA.
AC O62807; O77815; Q6L9M2;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Peroxisome proliferator-activated receptor gamma;
DE Short=PPAR-gamma;
DE AltName: Full=Nuclear receptor subfamily 1 group C member 3;
GN Name=PPARG; Synonyms=NR1C3;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Adipose tissue;
RX PubMed=9931452; DOI=10.1016/s0378-1119(98)00533-2;
RA Houseknecht K.L., Bidwell C.A., Portocarrero C.P., Spurlock M.E.;
RT "Expression and cDNA cloning of porcine peroxisome proliferator-activated
RT receptor gamma (PPARgamma).";
RL Gene 225:89-96(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=10481259; DOI=10.1016/s0305-0491(99)00077-2;
RA Ding S.T., McNeel R.L., Mersmann H.J.;
RT "Expression of porcine adipocyte transcripts: tissue distribution and
RT differentiation in vitro and in vivo.";
RL Comp. Biochem. Physiol. 123B:307-318(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=Duroc, and Norwegian Landrace; TISSUE=Adipocyte;
RX PubMed=9731203; DOI=10.1006/bbrc.1998.9212;
RA Grindflek E., Sundvold H., Klungland H., Lien S.;
RT "Characterisation of porcine peroxisome proliferator-activated receptors
RT gamma 1 and gamma 2: detection of breed and age differences in gene
RT expression.";
RL Biochem. Biophys. Res. Commun. 249:713-718(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Omi T., Brenig B., Kramer S.S., Iwamoto S., Stranzinger G.,
RA Neuenshwander S.;
RT "Identification and characterization of novel peroxisome proliferator-
RT activated receptor-gamma (PPAR-gamma) transcriptional variants in pig and
RT human.";
RL J. Anim. Breed. Genet. 122:45-53(2005).
CC -!- FUNCTION: Nuclear receptor that binds peroxisome proliferators such as
CC hypolipidemic drugs and fatty acids. Once activated by a ligand, the
CC nuclear receptor binds to DNA specific PPAR response elements (PPRE)
CC and modulates the transcription of its target genes, such as acyl-CoA
CC oxidase. It therefore controls the peroxisomal beta-oxidation pathway
CC of fatty acids. Key regulator of adipocyte differentiation and glucose
CC homeostasis. ARF6 acts as a key regulator of the tissue-specific
CC adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut
CC homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory
CC responses. Plays a role in the regulation of cardiovascular circadian
CC rhythms by regulating the transcription of ARNTL/BMAL1 in the blood
CC vessels. {ECO:0000250|UniProtKB:P37231, ECO:0000250|UniProtKB:P37238}.
CC -!- ACTIVITY REGULATION: PDPK1 activates its transcriptional activity
CC independently of its kinase activity. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with FOXO1 (acetylated form) (By similarity).
CC Heterodimer with other nuclear receptors, such as RXRA. The heterodimer
CC with the retinoic acid receptor RXRA is called adipocyte-specific
CC transcription factor ARF6. Interacts with NCOA6 coactivator, leading to
CC a strong increase in transcription of target genes. Interacts with
CC coactivator PPARBP, leading to a mild increase in transcription of
CC target genes. Interacts with NOCA7 in a ligand-inducible manner.
CC Interacts with NCOA1 and NCOA2 LXXLL motifs. Interacts with ASXL1,
CC ASXL2, DNTTIP2, FAM120B, MAP2K1/MEK1, NR0B2, PDPK1, PRDM16, PRMT2 and
CC TGFB1I1. Interacts (when activated by agonist) with PPP5C. Interacts
CC with HELZ2 and THRAP3; the interaction stimulates the transcriptional
CC activity of PPARG. Interacts with PER2, the interaction is ligand
CC dependent and blocks PPARG recruitment to target promoters. Interacts
CC with NOCT. Interacts with ACTN4. Interacts (when in the liganded
CC conformation) with GPS2 (By similarity). Interacts with CRY1 and CRY2
CC in a ligand-dependent manner (By similarity). In the absence of
CC hormonal ligand, interacts with TACC1 (By similarity).
CC {ECO:0000250|UniProtKB:P37231, ECO:0000250|UniProtKB:P37238}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC Cytoplasm {ECO:0000250}. Note=Redistributed from the nucleus to the
CC cytosol through a MAP2K1/MEK1-dependent manner. NOCT enhances its
CC nuclear translocation (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2;
CC IsoId=O62807-1; Sequence=Displayed;
CC Name=1;
CC IsoId=O62807-2; Sequence=VSP_003648;
CC -!- TISSUE SPECIFICITY: Highest expression in adipose tissue and lower in
CC spleen. Very low levels in kidney, intestine, lung and muscle.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:P37231}.
CC -!- PTM: Phosphorylated at basal conditions and dephosphorylated when
CC treated with the ligand. May be dephosphorylated by PPP5C. The
CC phosphorylated form may be inactive and dephosphorylation induces
CC adipogenic activity (By similarity). {ECO:0000250|UniProtKB:P37231}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; AF059245; AAC14348.1; -; mRNA.
DR EMBL; AF103946; AAD19577.1; -; mRNA.
DR EMBL; AJ006756; CAA07224.1; -; mRNA.
DR EMBL; AJ006757; CAA07225.1; -; mRNA.
DR EMBL; AB097930; BAD20646.1; -; mRNA.
DR PIR; JE0280; JE0280.
DR RefSeq; NP_999544.1; NM_214379.1. [O62807-1]
DR AlphaFoldDB; O62807; -.
DR BMRB; O62807; -.
DR SMR; O62807; -.
DR STRING; 9823.ENSSSCP00000012339; -.
DR PaxDb; O62807; -.
DR PRIDE; O62807; -.
DR Ensembl; ENSSSCT00055019853; ENSSSCP00055015667; ENSSSCG00055010097. [O62807-1]
DR Ensembl; ENSSSCT00065046377; ENSSSCP00065019910; ENSSSCG00065034050. [O62807-1]
DR Ensembl; ENSSSCT00070033522; ENSSSCP00070027999; ENSSSCG00070016976. [O62807-2]
DR Ensembl; ENSSSCT00070033549; ENSSSCP00070028013; ENSSSCG00070016976. [O62807-1]
DR Ensembl; ENSSSCT00070033567; ENSSSCP00070028026; ENSSSCG00070016976. [O62807-2]
DR Ensembl; ENSSSCT00070033589; ENSSSCP00070028038; ENSSSCG00070016976. [O62807-2]
DR Ensembl; ENSSSCT00070033621; ENSSSCP00070028059; ENSSSCG00070016976. [O62807-2]
DR Ensembl; ENSSSCT00070033629; ENSSSCP00070028066; ENSSSCG00070016976. [O62807-2]
DR GeneID; 397671; -.
DR KEGG; ssc:397671; -.
DR CTD; 5468; -.
DR eggNOG; KOG3575; Eukaryota.
DR HOGENOM; CLU_007368_4_2_1; -.
DR InParanoid; O62807; -.
DR OMA; WPINFGI; -.
DR OrthoDB; 1240230at2759; -.
DR TreeFam; TF316304; -.
DR Reactome; R-SSC-381340; Transcriptional regulation of white adipocyte differentiation.
DR Reactome; R-SSC-383280; Nuclear Receptor transcription pathway.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 13.
DR Genevisible; O62807; SS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:AgBase.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IBA:GO_Central.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0010742; P:macrophage derived foam cell differentiation; ISS:UniProtKB.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; IBA:GO_Central.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:AgBase.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IMP:AgBase.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:HGNC-UCL.
DR GO; GO:0045923; P:positive regulation of fatty acid metabolic process; IBA:GO_Central.
DR GO; GO:0032385; P:positive regulation of intracellular cholesterol transport; IMP:AgBase.
DR GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; IMP:AgBase.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:AgBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:AgBase.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IBA:GO_Central.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IMP:AgBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0033993; P:response to lipid; IBA:GO_Central.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IDA:GO_Central.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0050872; P:white fat cell differentiation; ISS:HGNC-UCL.
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; IPR003077; PPAR-gamma.
DR InterPro; IPR022590; PPARgamma_N.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF12577; PPARgamma_N; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR01288; PROXISOMEPAR.
DR PRINTS; PR01291; PROXISOMPAGR.
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 2: Evidence at transcript level;
KW Activator; Alternative splicing; Biological rhythms; Cytoplasm;
KW DNA-binding; Metal-binding; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..504
FT /note="Peroxisome proliferator-activated receptor gamma"
FT /id="PRO_0000053495"
FT DOMAIN 237..502
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 135..209
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 138..158
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 175..197
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 204..279
FT /note="Interaction with FAM120B"
FT /evidence="ECO:0000250"
FT MOTIF 494..502
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P37231"
FT MOD_RES 111
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P37238"
FT VAR_SEQ 1..29
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:9731203,
FT ECO:0000303|PubMed:9931452"
FT /id="VSP_003648"
FT CONFLICT 381
FT /note="K -> R (in Ref. 3; CAA07224/CAA07225)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="G -> R (in Ref. 3; CAA07224/CAA07225)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 57512 MW; 57C0BDE901493D31 CRC64;
MGETLGDSLI DPESDAFDTL SANISQEVTM VDTEMPFWPT NFGISSVDLS VMDDHSHSFD
IKPFTTVDFS SISTPHYEDI PFPRADPMVA DYKYDLKLQD YQSAIKVEPV SPPYYSEKTQ
LYNKPHEEPS NSLMAIECRV CGDKASGFHY GVHACEGCKG FFRRTIRLKL IYDRCDLNCR
IHKKSRNKCQ YCRFQKCLAV GMSHNAIRFG RMPQAEKEKL LAEISSDIDQ LNPESADLRA
LAKHLYDSYI KSFPLTKAKA RAILTGKTTD KSPFVIYDMN SLMMGEDKIK FKHITPLQEQ
SKEVAIRIFQ GCQFRSVEAV QEITEYAKNI PGFVNLDLND QVTLLKYGVH EIIYTMLASL
MNKDGVLISE GQGFMTREFL KSLRKPFGDF MEPKFEFAVK FNALELDDSD LAIFIAVIIL
SGDRPGLLNV KPIEDIQDNL LQALELQLKL NHPESSQLFA KLLQKMTDLR QIVTEHVQLL
QVIKKTETDM SLHPLLQEIY KDLY
