NR1H3_HUMAN
ID NR1H3_HUMAN Reviewed; 447 AA.
AC Q13133; A8K3J9; D3DQR1; Q8IW13; Q96H87;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 03-AUG-2022, entry version 220.
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;
GN Name=NR1H3; Synonyms=LXRA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=7744246; DOI=10.1101/gad.9.9.1033;
RA Willy P.J., Umesono K., Ong E.S., Evans R.M., Heyman R.A.,
RA Mangelsdorf D.J.;
RT "LXR, a nuclear receptor that defines a distinct retinoid response
RT pathway.";
RL Genes Dev. 9:1033-1045(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, and Placenta;
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 [6]
RP FUNCTION, INTERACTION WITH GPS2 AND NCOA2, AND MUTAGENESIS OF
RP 268-ILE--LYS-273 AND 438-LEU-LEU-439.
RX PubMed=19481530; DOI=10.1016/j.molcel.2009.05.006;
RA Jakobsson T., Venteclef N., Toresson G., Damdimopoulos A.E., Ehrlund A.,
RA Lou X., Sanyal S., Steffensen K.R., Gustafsson J.A., Treuter E.;
RT "GPS2 is required for cholesterol efflux by triggering histone
RT demethylation, LXR recruitment, and coregulator assembly at the ABCG1
RT locus.";
RL Mol. Cell 34:510-518(2009).
RN [7]
RP FUNCTION, INTERACTION WITH SIRT1 AND CCAR2, AND SUBCELLULAR LOCATION.
RX PubMed=25661920; DOI=10.1016/j.jsbmb.2015.02.001;
RA Sakurabashi A., Wada-Hiraike O., Hirano M., Fu H., Isono W., Fukuda T.,
RA Morita Y., Tanikawa M., Miyamoto Y., Oda K., Kawana K., Osuga Y., Fujii T.;
RT "CCAR2 negatively regulates nuclear receptor LXRalpha by competing with
RT SIRT1 deacetylase.";
RL J. Steroid Biochem. Mol. Biol. 149:80-88(2015).
CC -!- FUNCTION: Nuclear receptor that exhibits a ligand-dependent
CC transcriptional activation activity (PubMed:19481530, PubMed:25661920).
CC Interaction with retinoic acid receptor (RXR) shifts RXR from its role
CC as a silent DNA-binding partner to an active ligand-binding subunit in
CC mediating retinoid responses through target genes defined by LXRES (By
CC similarity). LXRES are DR4-type response elements characterized by
CC direct repeats of two similar hexanuclotide half-sites spaced by four
CC nucleotides (By similarity). Plays an important role in the regulation
CC of cholesterol homeostasis, regulating cholesterol uptake through
CC MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8
CC (PubMed:19481530). Interplays functionally with RORA for the regulation
CC of genes involved in liver metabolism (By similarity). Induces LPCAT3-
CC dependent phospholipid remodeling in endoplasmic reticulum (ER)
CC membranes of hepatocytes, driving SREBF1 processing and lipogenesis (By
CC similarity). Via LPCAT3, triggers the incorporation of arachidonate
CC into phosphatidylcholines of ER membranes, increasing membrane dynamics
CC and enabling triacylglycerols transfer to nascent very low-density
CC lipoprotein (VLDL) particles. Via LPCAT3 also counteracts lipid-induced
CC ER stress response and inflammation, likely by modulating SRC kinase
CC membrane compartmentalization and limiting the synthesis of lipid
CC inflammatory mediators (By similarity). {ECO:0000250|UniProtKB:Q9Z0Y9,
CC ECO:0000269|PubMed:19481530, ECO:0000269|PubMed:25661920}.
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 (PubMed:25661920). Interacts with GPS2 (PubMed:19481530).
CC {ECO:0000269|PubMed:19481530, ECO:0000269|PubMed:25661920}.
CC -!- INTERACTION:
CC Q13133; O60869: EDF1; NbExp=4; IntAct=EBI-781356, EBI-781301;
CC Q13133; O60341: KDM1A; NbExp=2; IntAct=EBI-781356, EBI-710124;
CC Q13133; Q99750: MDFI; NbExp=3; IntAct=EBI-781356, EBI-724076;
CC Q13133; Q15788: NCOA1; NbExp=15; IntAct=EBI-781356, EBI-455189;
CC Q13133; O75376: NCOR1; NbExp=2; IntAct=EBI-781356, EBI-347233;
CC Q13133; Q07869: PPARA; NbExp=5; IntAct=EBI-781356, EBI-78615;
CC Q13133; Q07869-1: PPARA; NbExp=2; IntAct=EBI-781356, EBI-21458428;
CC Q13133; Q03181: PPARD; NbExp=2; IntAct=EBI-781356, EBI-6426768;
CC Q13133; P37231: PPARG; NbExp=2; IntAct=EBI-781356, EBI-781384;
CC Q13133; P19793: RXRA; NbExp=8; IntAct=EBI-781356, EBI-78598;
CC Q13133; P28702: RXRB; NbExp=3; IntAct=EBI-781356, EBI-748576;
CC Q13133; P48443: RXRG; NbExp=7; IntAct=EBI-781356, EBI-712405;
CC Q13133; O43463: SUV39H1; NbExp=2; IntAct=EBI-781356, EBI-349968;
CC Q13133-2; P42858: HTT; NbExp=3; IntAct=EBI-12699353, EBI-466029;
CC Q13133-2; Q99750: MDFI; NbExp=3; IntAct=EBI-12699353, EBI-724076;
CC Q13133-3; O95817: BAG3; NbExp=3; IntAct=EBI-11952806, EBI-747185;
CC Q13133-3; G5E9A7: DMWD; NbExp=3; IntAct=EBI-11952806, EBI-10976677;
CC Q13133-3; O95872: GPANK1; NbExp=3; IntAct=EBI-11952806, EBI-751540;
CC Q13133-3; P02545: LMNA; NbExp=3; IntAct=EBI-11952806, EBI-351935;
CC Q13133-3; Q99750: MDFI; NbExp=3; IntAct=EBI-11952806, EBI-724076;
CC Q13133-3; P28702: RXRB; NbExp=6; IntAct=EBI-11952806, EBI-748576;
CC Q13133-3; P28702-3: RXRB; NbExp=3; IntAct=EBI-11952806, EBI-16429492;
CC Q13133-3; P48443: RXRG; NbExp=11; IntAct=EBI-11952806, EBI-712405;
CC Q13133-3; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-11952806, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:25661920}. Cytoplasm {ECO:0000250|UniProtKB:Q9Z0Y9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q13133-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13133-2; Sequence=VSP_003664;
CC Name=3;
CC IsoId=Q13133-3; Sequence=VSP_044960;
CC -!- TISSUE SPECIFICITY: Visceral organs specific expression. Strong
CC expression was found in liver, kidney and intestine followed by spleen
CC and to a lesser extent the adrenals.
CC -!- INDUCTION: By 9-cis retinoic acid (9CRA).
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}.
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DR EMBL; U22662; AAA85856.1; -; mRNA.
DR EMBL; AK290614; BAF83303.1; -; mRNA.
DR EMBL; AC018410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW67949.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW67942.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW67943.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW67944.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW67947.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW67948.1; -; Genomic_DNA.
DR EMBL; BC008819; AAH08819.1; -; mRNA.
DR EMBL; BC041172; AAH41172.1; -; mRNA.
DR CCDS; CCDS44584.1; -. [Q13133-2]
DR CCDS; CCDS44585.1; -. [Q13133-3]
DR CCDS; CCDS7929.1; -. [Q13133-1]
DR PIR; I38975; I38975.
DR RefSeq; NP_001123573.1; NM_001130101.2. [Q13133-2]
DR RefSeq; NP_001123574.1; NM_001130102.2. [Q13133-3]
DR RefSeq; NP_005684.2; NM_005693.3. [Q13133-1]
DR RefSeq; XP_005252762.1; XM_005252705.1.
DR RefSeq; XP_005252763.1; XM_005252706.1. [Q13133-1]
DR RefSeq; XP_005252764.1; XM_005252707.4.
DR RefSeq; XP_005252766.1; XM_005252709.1.
DR RefSeq; XP_005252767.1; XM_005252710.1.
DR RefSeq; XP_005252770.1; XM_005252713.3. [Q13133-2]
DR RefSeq; XP_006718175.1; XM_006718112.1.
DR RefSeq; XP_006718176.1; XM_006718113.1.
DR RefSeq; XP_006718178.1; XM_006718115.1.
DR RefSeq; XP_006718179.1; XM_006718116.1.
DR RefSeq; XP_011518107.1; XM_011519805.2. [Q13133-1]
DR RefSeq; XP_016872547.1; XM_017017058.1.
DR PDB; 1UHL; X-ray; 2.90 A; B=207-447.
DR PDB; 3IPQ; X-ray; 2.00 A; A=182-447.
DR PDB; 3IPS; X-ray; 2.26 A; A/B=182-447.
DR PDB; 3IPU; X-ray; 2.40 A; A/B=182-447.
DR PDB; 5AVI; X-ray; 2.70 A; A/C=182-447.
DR PDB; 5AVL; X-ray; 2.80 A; A=182-447.
DR PDB; 5HJS; X-ray; 1.72 A; A/B=182-447.
DR PDBsum; 1UHL; -.
DR PDBsum; 3IPQ; -.
DR PDBsum; 3IPS; -.
DR PDBsum; 3IPU; -.
DR PDBsum; 5AVI; -.
DR PDBsum; 5AVL; -.
DR PDBsum; 5HJS; -.
DR AlphaFoldDB; Q13133; -.
DR SMR; Q13133; -.
DR BioGRID; 115373; 55.
DR ComplexPortal; CPX-632; RXRalpha-LXRalpha nuclear hormone receptor complex.
DR ComplexPortal; CPX-716; RXRbeta-LXRalpha nuclear hormone receptor complex.
DR IntAct; Q13133; 39.
DR MINT; Q13133; -.
DR STRING; 9606.ENSP00000477707; -.
DR BindingDB; Q13133; -.
DR ChEMBL; CHEMBL2808; -.
DR DrugBank; DB08175; (2E,4E)-11-METHOXY-3,7,11-TRIMETHYLDODECA-2,4-DIENOIC ACID.
DR DrugBank; DB08063; 1-BENZYL-3-(4-METHOXYPHENYLAMINO)-4-PHENYLPYRROLE-2,5-DIONE.
DR DrugBank; DB11994; Diacerein.
DR DrugBank; DB07929; N-(TERT-BUTYL)-3,5-DIMETHYL-N'-[(5-METHYL-2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)CARBONYL]BENZOHYDRAZIDE.
DR DrugBank; DB13174; Rhein.
DR DrugBank; DB07080; TO-901317.
DR GuidetoPHARMACOLOGY; 602; -.
DR SwissLipids; SLP:000000836; -.
DR GlyGen; Q13133; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13133; -.
DR PhosphoSitePlus; Q13133; -.
DR BioMuta; NR1H3; -.
DR DMDM; 23503089; -.
DR EPD; Q13133; -.
DR jPOST; Q13133; -.
DR MassIVE; Q13133; -.
DR MaxQB; Q13133; -.
DR PaxDb; Q13133; -.
DR PeptideAtlas; Q13133; -.
DR PRIDE; Q13133; -.
DR ProteomicsDB; 59182; -. [Q13133-1]
DR ProteomicsDB; 59183; -. [Q13133-2]
DR ProteomicsDB; 70795; -.
DR Antibodypedia; 13611; 584 antibodies from 39 providers.
DR DNASU; 10062; -.
DR Ensembl; ENST00000395397.7; ENSP00000378793.3; ENSG00000025434.19. [Q13133-3]
DR Ensembl; ENST00000405853.7; ENSP00000384745.3; ENSG00000025434.19. [Q13133-2]
DR Ensembl; ENST00000407404.5; ENSP00000385801.1; ENSG00000025434.19. [Q13133-2]
DR Ensembl; ENST00000441012.7; ENSP00000387946.2; ENSG00000025434.19. [Q13133-1]
DR Ensembl; ENST00000467728.5; ENSP00000420656.1; ENSG00000025434.19. [Q13133-1]
DR GeneID; 10062; -.
DR KEGG; hsa:10062; -.
DR MANE-Select; ENST00000441012.7; ENSP00000387946.2; NM_005693.4; NP_005684.2.
DR UCSC; uc001nek.4; human. [Q13133-1]
DR CTD; 10062; -.
DR DisGeNET; 10062; -.
DR GeneCards; NR1H3; -.
DR HGNC; HGNC:7966; NR1H3.
DR HPA; ENSG00000025434; Low tissue specificity.
DR MalaCards; NR1H3; -.
DR MIM; 602423; gene.
DR neXtProt; NX_Q13133; -.
DR OpenTargets; ENSG00000025434; -.
DR PharmGKB; PA31751; -.
DR VEuPathDB; HostDB:ENSG00000025434; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000159068; -.
DR InParanoid; Q13133; -.
DR OMA; DFPVASH; -.
DR OrthoDB; 1137281at2759; -.
DR PhylomeDB; Q13133; -.
DR TreeFam; TF352167; -.
DR PathwayCommons; Q13133; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors. [Q13133-1]
DR Reactome; R-HSA-8866427; VLDLR internalisation and degradation.
DR Reactome; R-HSA-9029558; NR1H2 & NR1H3 regulate gene expression linked to lipogenesis.
DR Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-HSA-9031525; NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake.
DR Reactome; R-HSA-9031528; NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose.
DR Reactome; R-HSA-9623433; NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis.
DR Reactome; R-HSA-9632974; NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis.
DR SABIO-RK; Q13133; -.
DR SignaLink; Q13133; -.
DR SIGNOR; Q13133; -.
DR BioGRID-ORCS; 10062; 26 hits in 1108 CRISPR screens.
DR EvolutionaryTrace; Q13133; -.
DR GeneWiki; Liver_X_receptor_alpha; -.
DR GenomeRNAi; 10062; -.
DR Pharos; Q13133; Tchem.
DR PRO; PR:Q13133; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q13133; protein.
DR Bgee; ENSG00000025434; Expressed in right lobe of liver and 137 other tissues.
DR ExpressionAtlas; Q13133; baseline and differential.
DR Genevisible; Q13133; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0015485; F:cholesterol binding; TAS:BHF-UCL.
DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
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:0032810; F:sterol response element binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:BHF-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:BHF-UCL.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IDA:ComplexPortal.
DR GO; GO:0055088; P:lipid homeostasis; ISS:BHF-UCL.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; IMP:BHF-UCL.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:BHF-UCL.
DR GO; GO:0060336; P:negative regulation of interferon-gamma-mediated signaling pathway; NAS:BHF-UCL.
DR GO; GO:0032369; P:negative regulation of lipid transport; IMP:BHF-UCL.
DR GO; GO:0043031; P:negative regulation of macrophage activation; ISS:BHF-UCL.
DR GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; IC:BHF-UCL.
DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; ISS:BHF-UCL.
DR GO; GO:0048550; P:negative regulation of pinocytosis; IMP:BHF-UCL.
DR GO; GO:0045861; P:negative regulation of proteolysis; IEA:Ensembl.
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; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0036151; P:phosphatidylcholine acyl-chain remodeling; ISS:UniProtKB.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IDA:UniProtKB.
DR GO; GO:0032376; P:positive regulation of cholesterol transport; IDA:BHF-UCL.
DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0051006; P:positive regulation of lipoprotein lipase activity; IMP:BHF-UCL.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IMP:BHF-UCL.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IDA:BHF-UCL.
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; IDA:UniProtKB.
DR GO; GO:0032411; P:positive regulation of transporter activity; TAS:BHF-UCL.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0042752; P:regulation of circadian rhythm; TAS:BHF-UCL.
DR GO; GO:0032570; P:response to progesterone; IDA:BHF-UCL.
DR GO; GO:0055092; P:sterol homeostasis; ISS:BHF-UCL.
DR GO; GO:0070328; P:triglyceride homeostasis; ISS:BHF-UCL.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR IDEAL; IID00243; -.
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 3D-structure; Activator; Alternative splicing; Cytoplasm; DNA-binding;
KW Metal-binding; Nucleus; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..447
FT /note="Oxysterols receptor LXR-alpha"
FT /id="PRO_0000053535"
FT DOMAIN 209..447
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 95..170
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 98..118
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 134..158
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..96
FT /note="Transactivation AF-1; required for ligand-
FT independent transactivation function"
FT /evidence="ECO:0000269|PubMed:25661920"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 180..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 205..447
FT /note="Transactivation AF-2; required for ligand-dependent
FT transactivation function; mediates interaction with CCAR2"
FT /evidence="ECO:0000269|PubMed:25661920"
FT VAR_SEQ 1..45
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044960"
FT VAR_SEQ 237..296
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_003664"
FT VARIANT 52
FT /note="G -> V (in dbSNP:rs41481445)"
FT /id="VAR_050580"
FT MUTAGEN 268..273
FT /note="IVDFAK->EVDFAE: Abolishes interaction with NCOA2
FT without affecting interaction with GPS2; when associated
FT with 438-A-A-439."
FT /evidence="ECO:0000269|PubMed:19481530"
FT MUTAGEN 438..439
FT /note="LL->AA: Abolishes interaction with NCOA2 without
FT affecting interaction with GPS2; when associated with 268-
FT A--A-273."
FT /evidence="ECO:0000269|PubMed:19481530"
FT CONFLICT 196
FT /note="A -> R (in Ref. 1; AAA85856)"
FT /evidence="ECO:0000305"
FT HELIX 208..220
FT /evidence="ECO:0007829|PDB:5HJS"
FT HELIX 229..233
FT /evidence="ECO:0007829|PDB:3IPU"
FT HELIX 247..272
FT /evidence="ECO:0007829|PDB:5HJS"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:5HJS"
FT HELIX 283..304
FT /evidence="ECO:0007829|PDB:5HJS"
FT TURN 308..311
FT /evidence="ECO:0007829|PDB:5HJS"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:5HJS"
FT TURN 316..318
FT /evidence="ECO:0007829|PDB:5HJS"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:5HJS"
FT HELIX 323..328
FT /evidence="ECO:0007829|PDB:5HJS"
FT HELIX 333..349
FT /evidence="ECO:0007829|PDB:5HJS"
FT HELIX 353..364
FT /evidence="ECO:0007829|PDB:5HJS"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:1UHL"
FT HELIX 375..396
FT /evidence="ECO:0007829|PDB:5HJS"
FT HELIX 403..430
FT /evidence="ECO:0007829|PDB:5HJS"
FT HELIX 437..443
FT /evidence="ECO:0007829|PDB:5HJS"
SQ SEQUENCE 447 AA; 50396 MW; 0D27B237440F8C9C CRC64;
MSLWLGAPVP DIPPDSAVEL WKPGAQDASS QAQGGSSCIL REEARMPHSA GGTAGVGLEA
AEPTALLTRA EPPSEPTEIR PQKRKKGPAP KMLGNELCSV CGDKASGFHY NVLSCEGCKG
FFRRSVIKGA HYICHSGGHC PMDTYMRRKC QECRLRKCRQ AGMREECVLS EEQIRLKKLK
RQEEEQAHAT SLPPRASSPP QILPQLSPEQ LGMIEKLVAA QQQCNRRSFS DRLRVTPWPM
APDPHSREAR QQRFAHFTEL AIVSVQEIVD FAKQLPGFLQ LSREDQIALL KTSAIEVMLL
ETSRRYNPGS ESITFLKDFS YNREDFAKAG LQVEFINPIF EFSRAMNELQ LNDAEFALLI
AISIFSADRP NVQDQLQVER LQHTYVEALH AYVSIHHPHD RLMFPRMLMK LVSLRTLSSV
HSEQVFALRL QDKKLPPLLS EIWDVHE
