NR1H2_RAT
ID NR1H2_RAT Reviewed; 446 AA.
AC Q62755; Q62694;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Oxysterols receptor LXR-beta;
DE AltName: Full=Liver X receptor beta;
DE AltName: Full=Nuclear receptor subfamily 1 group H member 2;
DE AltName: Full=Orphan nuclear receptor OR-1;
DE AltName: Full=Ubiquitously-expressed nuclear receptor;
DE Short=UR;
GN Name=Nr1h2; Synonyms=Lxrb;
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 STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=7892230; DOI=10.1073/pnas.92.6.2096;
RA Teboul M., Enmark E., Li Q., Wikstroem A.-C., Pelto-Huikko M.,
RA Gustafsson J.-A.;
RT "OR-1, a member of the nuclear receptor superfamily that interacts with the
RT 9-cis-retinoic acid receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:2096-2100(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Vagina;
RX PubMed=7971966; DOI=10.1073/pnas.91.23.10809;
RA Song C., Kokontis J.M., Hiipakka R.A., Liao S.;
RT "Ubiquitous receptor: a receptor that modulates gene activation by retinoic
RT acid and thyroid hormone receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:10809-10813(1994).
CC -!- FUNCTION: Nuclear receptor that exhibits a ligand-dependent
CC transcriptional activation activity (By similarity). Binds
CC preferentially to double-stranded oligonucleotide direct repeats having
CC the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4).
CC Regulates cholesterol uptake through MYLIP-dependent ubiquitination of
CC LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA
CC for the regulation of genes involved in liver metabolism (By
CC similarity). Induces LPCAT3-dependent phospholipid remodeling in
CC endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1
CC processing and lipogenesis (By similarity). Via LPCAT3, triggers the
CC incorporation of arachidonate into phosphatidylcholines of ER
CC membranes, increasing membrane dynamics and enabling triacylglycerols
CC transfer to nascent very low-density lipoprotein (VLDL) particles. Via
CC LPCAT3 also counteracts lipid-induced ER stress response and
CC inflammation, likely by modulating SRC kinase membrane
CC compartmentalization and limiting the synthesis of lipid inflammatory
CC mediators (By similarity). Plays an anti-inflammatory role during the
CC hepatic acute phase response by acting as a corepressor: inhibits the
CC hepatic acute phase response by preventing dissociation of the N-Cor
CC corepressor complex (By similarity). {ECO:0000250|UniProtKB:P55055,
CC ECO:0000250|UniProtKB:Q60644}.
CC -!- SUBUNIT: Forms a heterodimer with RXR. Interacts with CCAR2 (via N-
CC terminus) in a ligand-independent manner. Interacts (when sumoylated)
CC with GPS2; interaction with GPS2 onto hepatic acute phase protein
CC promoters prevents N-Cor corepressor complex dissociation (By
CC similarity). Interacts with ABCA12 and ABCA1; this interaction is
CC required for ABCA1 localization to the cell surface and is necessary
CC for its normal activity and stability (By similarity).
CC {ECO:0000250|UniProtKB:P55055}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC -!- PTM: Sumoylated by SUMO2 at Lys-395 and Lys-433 during the hepatic
CC acute phase response, leading to promote interaction with GPS2 and
CC prevent N-Cor corepressor complex dissociation.
CC {ECO:0000250|UniProtKB:P55055}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; U20389; AAA69522.1; -; mRNA.
DR EMBL; U14533; AAA52361.1; -; mRNA.
DR PIR; I59354; I59354.
DR RefSeq; NP_113814.1; NM_031626.1.
DR AlphaFoldDB; Q62755; -.
DR SMR; Q62755; -.
DR STRING; 10116.ENSRNOP00000026862; -.
DR BindingDB; Q62755; -.
DR ChEMBL; CHEMBL4105785; -.
DR PhosphoSitePlus; Q62755; -.
DR PaxDb; Q62755; -.
DR PRIDE; Q62755; -.
DR GeneID; 58851; -.
DR KEGG; rno:58851; -.
DR UCSC; RGD:61906; rat.
DR CTD; 7376; -.
DR RGD; 61906; Nr1h2.
DR VEuPathDB; HostDB:ENSRNOG00000019812; -.
DR eggNOG; KOG3575; Eukaryota.
DR HOGENOM; CLU_007368_12_4_1; -.
DR InParanoid; Q62755; -.
DR OMA; GMREQCE; -.
DR OrthoDB; 1137281at2759; -.
DR PhylomeDB; Q62755; -.
DR TreeFam; TF352167; -.
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:Q62755; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000019812; Expressed in thymus and 20 other tissues.
DR Genevisible; Q62755; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0034191; F:apolipoprotein A-I receptor binding; ISO:RGD.
DR GO; GO:0051117; F:ATPase binding; ISO:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:RGD.
DR GO; GO:0004879; F:nuclear receptor activity; ISO:RGD.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; IDA:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IMP:NTNU_SB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0044255; P:cellular lipid metabolic process; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0055088; P:lipid homeostasis; 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:0010629; P:negative regulation of gene expression; IDA:RGD.
DR GO; GO:0032369; P:negative regulation of lipid transport; 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: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; ISO:RGD.
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:0010628; P:positive regulation of gene expression; IDA:RGD.
DR GO; GO:0090108; P:positive regulation of high-density lipoprotein particle assembly; ISO:RGD.
DR GO; GO:0010884; P:positive regulation of lipid storage; ISO:RGD.
DR GO; GO:0051006; P:positive regulation of lipoprotein lipase activity; ISO:RGD.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0090187; P:positive regulation of pancreatic juice secretion; ISO:RGD.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IEA:Ensembl.
DR GO; GO:0090340; P:positive regulation of secretion of lysosomal enzymes; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IDA: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 2: Evidence at transcript level;
KW Activator; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Receptor;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..446
FT /note="Oxysterols receptor LXR-beta"
FT /id="PRO_0000053534"
FT DOMAIN 208..446
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 75..152
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 78..98
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 116..140
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..76
FT /note="Transactivation AF-1; required for ligand-
FT independent transactivation function"
FT /evidence="ECO:0000250|UniProtKB:P55055"
FT REGION 1..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 160..201
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 205..446
FT /note="Transactivation AF-2; required for ligand-dependent
FT transactivation function; mediates interaction with CCAR2"
FT /evidence="ECO:0000250|UniProtKB:P55055"
FT COMPBIAS 1..32
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 55..69
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 179..201
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 395
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P55055"
FT CROSSLNK 433
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P55055"
FT CONFLICT 33
FT /note="G -> V (in Ref. 2; AAA52361)"
FT /evidence="ECO:0000305"
FT CONFLICT 52..54
FT /note="Missing (in Ref. 2; AAA52361)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="A -> V (in Ref. 2; AAA52361)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 446 AA; 49736 MW; 13DF6DC2F0F5FA4D CRC64;
MSSPTSSLDT PLPGNGSPQP STSSTSPTIK EEGQETDPPP GSEGSSSAYI VVILEPEDEP
ERKRKKGPAP KMLGHELCRV CGDKASGFHY NVLSCEGCKG FFRRSVVHGG AGRYACRGSG
TCQMDAFMRR KCQLCRLRKC KEAGMREQCV LSEEQIRKKK IQKQQQQQPP PPTEPASGSS
ARPAASPGTS EASSQGSGEG EGIQLTAAQE LMIQQLVAAQ LQCNKRSFSD QPKVTPWPLG
ADPQSRDARQ QRFAHFTELA IISVQEIVDF AKQVPGFLQL GREDQIALLK ASTIEIMLLE
TARRYNHETE CITFLKDFTY SKDDFHRAGL QVEFINPIFE FSRAMRRLGL DDAEYALLIA
INIFSADRPN VQEPSRVEAL QQPYVEALLS YTRIKRPQDQ LRFPRMLMKL VSLRTLSSVH
SEQVFALRLQ DKKLPPLLSE IWDVHE
