NR1H2_MOUSE
ID NR1H2_MOUSE Reviewed; 446 AA.
AC Q60644;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 188.
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=Retinoid X receptor-interacting protein No.15;
DE AltName: Full=Ubiquitously-expressed nuclear receptor;
GN Name=Nr1h2; Synonyms=Lxrb, Rip15, Unr, Unr2;
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 TISSUE=Liver;
RX PubMed=7760852; DOI=10.1210/mend.9.1.7760852;
RA Seol W., Choi H.S., Moore D.D.;
RT "Isolation of proteins that interact specifically with the retinoid X
RT receptor: two novel orphan receptors.";
RL Mol. Endocrinol. 9:72-85(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ; TISSUE=Liver;
RX PubMed=10675617; DOI=10.1016/s0378-1119(99)00555-7;
RA Alberti S., Steffensen K.R., Gustafsson J.-A.;
RT "Structural characterisation of the mouse nuclear oxysterol receptor genes
RT LXRalpha and LXRbeta.";
RL Gene 243:93-103(2000).
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 FUNCTION IN METABOLISM REGULATION.
RX PubMed=18055760; DOI=10.1124/mol.107.040741;
RA Wada T., Kang H.S., Angers M., Gong H., Bhatia S., Khadem S., Ren S.,
RA Ellis E., Strom S.C., Jetten A.M., Xie W.;
RT "Identification of oxysterol 7alpha-hydroxylase (Cyp7b1) as a novel
RT retinoid-related orphan receptor alpha (RORalpha) (NR1F1) target gene and a
RT functional cross-talk between RORalpha and liver X receptor (NR1H3).";
RL Mol. Pharmacol. 73:891-899(2008).
RN [5]
RP FUNCTION.
RX PubMed=19520913; DOI=10.1126/science.1168974;
RA Zelcer N., Hong C., Boyadjian R., Tontonoz P.;
RT "LXR regulates cholesterol uptake through Idol-dependent ubiquitination of
RT the LDL receptor.";
RL Science 325:100-104(2009).
RN [6]
RP FUNCTION.
RX PubMed=20427281; DOI=10.1074/jbc.m110.123729;
RA Hong C., Duit S., Jalonen P., Out R., Scheer L., Sorrentino V.,
RA Boyadjian R., Rodenburg K.W., Foley E., Korhonen L., Lindholm D., Nimpf J.,
RA van Berkel T.J., Tontonoz P., Zelcer N.;
RT "The E3 ubiquitin ligase IDOL induces the degradation of the low density
RT lipoprotein receptor family members VLDLR and ApoER2.";
RL J. Biol. Chem. 285:19720-19726(2010).
RN [7]
RP FUNCTION.
RX PubMed=24206663; DOI=10.1016/j.cmet.2013.10.002;
RA Rong X., Albert C.J., Hong C., Duerr M.A., Chamberlain B.T., Tarling E.J.,
RA Ito A., Gao J., Wang B., Edwards P.A., Jung M.E., Ford D.A., Tontonoz P.;
RT "LXRs regulate ER stress and inflammation through dynamic modulation of
RT membrane phospholipid composition.";
RL Cell Metab. 18:685-697(2013).
RN [8]
RP FUNCTION.
RX PubMed=25806685; DOI=10.7554/elife.06557;
RA Rong X., Wang B., Dunham M.M., Hedde P.N., Wong J.S., Gratton E.,
RA Young S.G., Ford D.A., Tontonoz P.;
RT "Lpcat3-dependent production of arachidonoyl phospholipids is a key
RT determinant of triglyceride secretion.";
RL Elife 4:0-0(2015).
RN [9]
RP FUNCTION.
RX PubMed=28846071; DOI=10.1172/jci93616;
RA Rong X., Wang B., Palladino E.N., de Aguiar Vallim T.Q., Ford D.A.,
RA Tontonoz P.;
RT "ER phospholipid composition modulates lipogenesis during feeding and in
RT obesity.";
RL J. Clin. Invest. 127:3640-3651(2017).
CC -!- FUNCTION: Nuclear receptor that exhibits a ligand-dependent
CC transcriptional activation activity (PubMed:18055760, PubMed:19520913,
CC PubMed:20427281). Binds preferentially to double-stranded
CC oligonucleotide direct repeats having the consensus half-site sequence
CC 5'-AGGTCA-3' and 4-nt spacing (DR-4) (PubMed:18055760, PubMed:19520913,
CC PubMed:20427281). Regulates cholesterol uptake through MYLIP-dependent
CC ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8
CC (PubMed:18055760, PubMed:19520913, PubMed:20427281). Interplays
CC functionally with RORA for the regulation of genes involved in liver
CC metabolism (PubMed:18055760, PubMed:19520913, PubMed:20427281,
CC PubMed:24206663, PubMed:28846071). Induces LPCAT3-dependent
CC phospholipid remodeling in endoplasmic reticulum (ER) membranes of
CC hepatocytes, driving SREBF1 processing and lipogenesis
CC (PubMed:28846071, PubMed:25806685). 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
CC (PubMed:25806685). Via LPCAT3 also counteracts lipid-induced ER stress
CC response and inflammation, likely by modulating SRC kinase membrane
CC compartmentalization and limiting the synthesis of lipid inflammatory
CC mediators (PubMed:24206663). 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:0000269|PubMed:18055760, ECO:0000269|PubMed:19520913,
CC ECO:0000269|PubMed:20427281, ECO:0000269|PubMed:24206663,
CC ECO:0000269|PubMed:25806685, ECO:0000269|PubMed:28846071}.
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 -!- INTERACTION:
CC Q60644; Q96EB6: SIRT1; Xeno; NbExp=2; IntAct=EBI-5276809, EBI-1802965;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
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; U09419; AAC52164.1; -; mRNA.
DR EMBL; AJ132602; CAB51924.1; -; Genomic_DNA.
DR EMBL; BC066025; AAH66025.1; -; mRNA.
DR CCDS; CCDS21211.1; -.
DR PIR; I49021; I49021.
DR RefSeq; NP_001272446.1; NM_001285517.1.
DR RefSeq; NP_001272447.1; NM_001285518.1.
DR RefSeq; NP_001272448.1; NM_001285519.1.
DR RefSeq; NP_033499.1; NM_009473.3.
DR RefSeq; XP_006540867.1; XM_006540804.3.
DR AlphaFoldDB; Q60644; -.
DR SMR; Q60644; -.
DR BioGRID; 204450; 4.
DR ComplexPortal; CPX-679; RXRalpha-LXRbeta nuclear hormone receptor complex.
DR ComplexPortal; CPX-706; RXRbeta-LXRbeta nuclear hormone receptor complex.
DR DIP; DIP-444N; -.
DR IntAct; Q60644; 6.
DR MINT; Q60644; -.
DR STRING; 10090.ENSMUSP00000103544; -.
DR BindingDB; Q60644; -.
DR ChEMBL; CHEMBL2417346; -.
DR GuidetoPHARMACOLOGY; 601; -.
DR PhosphoSitePlus; Q60644; -.
DR EPD; Q60644; -.
DR MaxQB; Q60644; -.
DR PaxDb; Q60644; -.
DR PRIDE; Q60644; -.
DR ProteomicsDB; 295517; -.
DR Antibodypedia; 9326; 406 antibodies from 42 providers.
DR DNASU; 22260; -.
DR Ensembl; ENSMUST00000073488; ENSMUSP00000073188; ENSMUSG00000060601.
DR Ensembl; ENSMUST00000107912; ENSMUSP00000103545; ENSMUSG00000060601.
DR Ensembl; ENSMUST00000167197; ENSMUSP00000126788; ENSMUSG00000060601.
DR GeneID; 22260; -.
DR KEGG; mmu:22260; -.
DR UCSC; uc009gpz.2; mouse.
DR CTD; 7376; -.
DR MGI; MGI:1352463; Nr1h2.
DR VEuPathDB; HostDB:ENSMUSG00000060601; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000161465; -.
DR InParanoid; Q60644; -.
DR OMA; GMREQCE; -.
DR OrthoDB; 1137281at2759; -.
DR PhylomeDB; Q60644; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-MMU-8866427; VLDLR internalisation and degradation.
DR Reactome; R-MMU-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-MMU-9623433; NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis.
DR BioGRID-ORCS; 22260; 6 hits in 77 CRISPR screens.
DR ChiTaRS; Nr1h2; mouse.
DR PRO; PR:Q60644; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q60644; protein.
DR Bgee; ENSMUSG00000060601; Expressed in granulocyte and 249 other tissues.
DR ExpressionAtlas; Q60644; baseline and differential.
DR Genevisible; Q60644; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0034191; F:apolipoprotein A-I receptor binding; ISO:MGI.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:MGI.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; IDA:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
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; IDA:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:BHF-UCL.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IC:ComplexPortal.
DR GO; GO:0055088; P:lipid homeostasis; IMP:BHF-UCL.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IC:ComplexPortal.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; ISO:MGI.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IGI:YuBioLab.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0032369; P:negative regulation of lipid transport; ISO:MGI.
DR GO; GO:0048550; P:negative regulation of pinocytosis; ISO:MGI.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:BHF-UCL.
DR GO; GO:1903573; P:negative regulation of response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0036151; P:phosphatidylcholine acyl-chain remodeling; IMP:UniProtKB.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IDA:BHF-UCL.
DR GO; GO:0032376; P:positive regulation of cholesterol transport; ISO:MGI.
DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0090108; P:positive regulation of high-density lipoprotein particle assembly; IDA:BHF-UCL.
DR GO; GO:0010884; P:positive regulation of lipid storage; IMP:BHF-UCL.
DR GO; GO:0051006; P:positive regulation of lipoprotein lipase activity; ISO:MGI.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:ARUK-UCL.
DR GO; GO:0090187; P:positive regulation of pancreatic juice secretion; IMP:BHF-UCL.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISO:MGI.
DR GO; GO:0090340; P:positive regulation of secretion of lysosomal enzymes; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; ISO:MGI.
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; 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_0000053533"
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 159..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"
SQ SEQUENCE 446 AA; 49720 MW; 73153E635302C9DF CRC64;
MSSPTSSLDT PVPGNGSPQP STSATSPTIK EEGQETDPPP GSEGSSSAYI VVILEPEDEP
ERKRKKGPAP KMLGHELCRV CGDKASGFHY NVLSCEGCKG FFRRSVVHGG AGRYACRGSG
TCQMDAFMRR KCQLCRLRKC KEAGMREQCV LSEEQIRKKR IQKQQQQQPP PPSEPAASSS
GRPAASPGTS 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
