NR1H3_RAT
ID NR1H3_RAT Reviewed; 445 AA.
AC Q62685;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Oxysterols receptor LXR-alpha;
DE AltName: Full=Liver X receptor alpha;
DE AltName: Full=Nuclear receptor subfamily 1 group H member 3;
DE AltName: Full=RLD-1;
GN Name=Nr1h3; Synonyms=Lxra;
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].
RC TISSUE=Liver;
RX PubMed=7935418; DOI=10.1128/mcb.14.10.7025-7035.1994;
RA Apfel R.H., Benbrook D., Lernhardt E., Ortiz M.A., Salbert G., Pfahl M.;
RT "A novel orphan receptor specific for a subset of thyroid hormone-
RT responsive elements and its interaction with the retinoid/thyroid hormone
RT receptor subfamily.";
RL Mol. Cell. Biol. 14:7025-7035(1994).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-191, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Nuclear receptor that exhibits a ligand-dependent
CC transcriptional activation activity. Interaction with retinoic acid
CC receptor (RXR) shifts RXR from its role as a silent DNA-binding partner
CC to an active ligand-binding subunit in mediating retinoid responses
CC through target genes defined by LXRES. LXRES are DR4-type response
CC elements characterized by direct repeats of two similar hexanuclotide
CC half-sites spaced by four nucleotides. Plays an important role in the
CC regulation of cholesterol homeostasis, regulating cholesterol uptake
CC through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8.
CC Interplays functionally with RORA for the regulation of genes involved
CC in liver metabolism (By similarity). Induces LPCAT3-dependent
CC phospholipid remodeling in endoplasmic reticulum (ER) membranes of
CC hepatocytes, driving SREBF1 processing and lipogenesis (By similarity).
CC Via LPCAT3, triggers the incorporation of arachidonate into
CC phosphatidylcholines of ER membranes, increasing membrane dynamics and
CC enabling triacylglycerols transfer to nascent very low-density
CC lipoprotein (VLDL) particles (By similarity). Via LPCAT3 also
CC counteracts lipid-induced ER stress response and inflammation, likely
CC by modulating SRC kinase membrane compartmentalization and limiting the
CC synthesis of lipid inflammatory mediators (By similarity).
CC {ECO:0000250|UniProtKB:Q13133, ECO:0000250|UniProtKB:Q9Z0Y9}.
CC -!- SUBUNIT: Heterodimer of NR1H3 and RXR (retinoic acid receptor).
CC Interacts with CCAR2 (via N-terminus) in a ligand-independent manner.
CC Interacts with SIRT1 and this interaction is inhibited by CCAR2.
CC {ECO:0000250|UniProtKB:Q13133}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Z0Y9,
CC ECO:0000255|PROSITE-ProRule:PRU00407}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9Z0Y9}.
CC -!- TISSUE SPECIFICITY: In adults it is expressed in spleen, pituitary,
CC lung, liver, and fat. Weaker expression is observed in several other
CC tissues.
CC -!- PTM: Ubiquitinated leading to its degradation by the proteasome.
CC {ECO:0000250|UniProtKB:Q9Z0Y9}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U11685; AAA53633.1; -; mRNA.
DR PIR; A56043; A56043.
DR AlphaFoldDB; Q62685; -.
DR SMR; Q62685; -.
DR STRING; 10116.ENSRNOP00000018154; -.
DR ChEMBL; CHEMBL4523336; -.
DR iPTMnet; Q62685; -.
DR PhosphoSitePlus; Q62685; -.
DR PaxDb; Q62685; -.
DR PRIDE; Q62685; -.
DR UCSC; RGD:61909; rat.
DR RGD; 61909; Nr1h3.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q62685; -.
DR PhylomeDB; Q62685; -.
DR Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-RNO-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-RNO-8866427; VLDLR internalisation and degradation.
DR Reactome; R-RNO-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-RNO-9623433; NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis.
DR PRO; PR:Q62685; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; 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:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; IPI:RGD.
DR GO; GO:0003707; F:nuclear steroid receptor activity; TAS:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0032810; F:sterol response element binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0043277; P:apoptotic cell clearance; ISO:RGD.
DR GO; GO:0038183; P:bile acid signaling pathway; IEP:RGD.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0044255; P:cellular lipid metabolic process; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IEP:RGD.
DR GO; GO:0055088; P:lipid homeostasis; ISO:RGD.
DR GO; GO:0006629; P:lipid metabolic process; IEP:RGD.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; ISO:RGD.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032369; P:negative regulation of lipid transport; ISO:RGD.
DR GO; GO:0043031; P:negative regulation of macrophage activation; ISO:RGD.
DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; ISO:RGD.
DR GO; GO:0048550; P:negative regulation of pinocytosis; ISO:RGD.
DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:RGD.
DR GO; GO:1903573; P:negative regulation of response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0090341; P:negative regulation of secretion of lysosomal enzymes; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0036151; P:phosphatidylcholine acyl-chain remodeling; ISS:UniProtKB.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISS:UniProtKB.
DR GO; GO:0032376; P:positive regulation of cholesterol transport; ISO:RGD.
DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; ISO:RGD.
DR GO; GO:0051006; P:positive regulation of lipoprotein lipase activity; ISO:RGD.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0070723; P:response to cholesterol; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0032570; P:response to progesterone; ISO:RGD.
DR GO; GO:0055092; P:sterol homeostasis; ISO:RGD.
DR GO; GO:0070328; P:triglyceride homeostasis; ISO:RGD.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR023257; Liver_X_rcpt.
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 Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR02034; LIVERXRECPTR.
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; Cytoplasm; DNA-binding; Metal-binding; Nucleus; Phosphoprotein;
KW Receptor; Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..445
FT /note="Oxysterols receptor LXR-alpha"
FT /id="PRO_0000053537"
FT DOMAIN 207..445
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 93..168
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 96..116
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 132..156
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..94
FT /note="Transactivation AF-1; required for ligand-
FT independent transactivation function"
FT /evidence="ECO:0000250|UniProtKB:Q13133"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 62..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 178..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 203..445
FT /note="Transactivation AF-2; required for ligand-dependent
FT transactivation function; mediates interaction with CCAR2"
FT /evidence="ECO:0000250|UniProtKB:Q13133"
FT COMPBIAS 184..200
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 445 AA; 50555 MW; 131A84AB142AEA82 CRC64;
MSLWLEAAVP DVSPDSATEL WKTEPQDAGD QGGNTCILRE EARMPQSTGG ALRIGLESSE
PTALLPRAET LPEPTELRPQ KRKKGPAPKM LGNELCSVCG DKASAFHYNV LSCEGCKGFF
RRSVIKGARY ICHSGGHCPM DTYMRRKCQE CRLRKCRHAG MREECVLSEE QIRLKKLKRQ
EEEQAQATSV SPRVSSPPQV LPQLSPEQLG MIEKLVAAQQ QCNRRSFSDR LRVTPWPIAP
DPQSREARQQ RFAHFTELAI VSVQEIVDFA KQLPGFLQLS REDQIALLKT SAIEVMLLET
SRRYNPGSES ITFLKDFSYN REDFAKAGLQ VEFINPIFEF SRSMNELQLN DAEFALLIAI
SIFSADRPNV QDQLQVERLQ HTYVEALHAY VSINHPHDRL MFPRMLMKLV SLRTLSSVHS
EQVFALRLQD KKLPPLLSEI WDVHE
