NR1H3_BOVIN
ID NR1H3_BOVIN Reviewed; 447 AA.
AC Q5E9B6;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 134.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
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 -!- 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; BT021004; AAX09021.1; -; mRNA.
DR EMBL; BC103207; AAI03208.1; -; mRNA.
DR RefSeq; NP_001014861.1; NM_001014861.1.
DR AlphaFoldDB; Q5E9B6; -.
DR SMR; Q5E9B6; -.
DR STRING; 9913.ENSBTAP00000014131; -.
DR PaxDb; Q5E9B6; -.
DR Ensembl; ENSBTAT00000014131; ENSBTAP00000014131; ENSBTAG00000010681.
DR Ensembl; ENSBTAT00000071739; ENSBTAP00000060937; ENSBTAG00000010681.
DR GeneID; 507176; -.
DR KEGG; bta:507176; -.
DR CTD; 10062; -.
DR VEuPathDB; HostDB:ENSBTAG00000010681; -.
DR VGNC; VGNC:32231; NR1H3.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000159068; -.
DR HOGENOM; CLU_007368_12_4_1; -.
DR InParanoid; Q5E9B6; -.
DR OMA; DFPVASH; -.
DR OrthoDB; 1137281at2759; -.
DR TreeFam; TF352167; -.
DR Reactome; R-BTA-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-BTA-8866427; VLDLR internalisation and degradation.
DR Reactome; R-BTA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-BTA-9623433; NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis.
DR Proteomes; UP000009136; Chromosome 15.
DR Bgee; ENSBTAG00000010681; Expressed in lung and 104 other tissues.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IEA:Ensembl.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IEA:Ensembl.
DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; ISS:AgBase.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:AgBase.
DR GO; GO:0032810; F:sterol response element binding; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0043277; P:apoptotic cell clearance; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; IEA:Ensembl.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IEA:Ensembl.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IBA:GO_Central.
DR GO; GO:0032369; P:negative regulation of lipid transport; IEA:Ensembl.
DR GO; GO:0043031; P:negative regulation of macrophage activation; IEA:Ensembl.
DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; IEA:Ensembl.
DR GO; GO:0048550; P:negative regulation of pinocytosis; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
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:0045723; P:positive regulation of fatty acid biosynthetic process; IEA:Ensembl.
DR GO; GO:0051006; P:positive regulation of lipoprotein lipase activity; IEA:Ensembl.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IEA:Ensembl.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl.
DR GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl.
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; Cytoplasm; DNA-binding; Metal-binding; Nucleus; Receptor;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..447
FT /note="Oxysterols receptor LXR-alpha"
FT /id="PRO_0000246174"
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:0000250|UniProtKB:Q13133"
FT REGION 1..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 178..203
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:0000250|UniProtKB:Q13133"
FT COMPBIAS 28..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 447 AA; 50529 MW; CAD6614CAC2EF5F0 CRC64;
MSLWLEAPVP DVSPDSAVEL WEPDAQDASS QPLGSSKCIL REESSTPQSA GDTSRMGLEA
PEPTALLPGV EAPPESTELR PQKRKKGPAP KMLGNELCSV CGDKASGFHY NVLSCEGCKG
FFRRSVIKGA RYVCHSGGHC PMDTYMRRKC QECRLRKCRQ AGMREECVLS EEQIRLKKMK
RQEEEQAQAT SAPPRASSPP QVLPQLSPEQ LGMIEKLVAA QQLCNRRSFS DQLRVTPWPM
APDPQSREAR QQRFAHFTEL AIVSVQEIVD FAKQLPGFLQ LSREDQIALL KTSAIEVMLL
ETSRRYNPGS ESITFLKDFS YNREDFAKAG LQVEFINPIF EFSRAMNELQ LNDAEFALLI
AISIFSADRP NVQDQLQVER LQHTYVEALH AYVSIHHPHD RLMFPRMLMK LVSLRTLSSV
HSEQVFALRL QDKKLPPLLS EIWDVHE
