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Protein

Oxysterols receptor LXR-alpha

Gene

Nr1h3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Nuclear receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism. Exhibits a ligand-dependent transcriptional activation activity (By similarity).By similarity3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi93 – 16876Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri96 – 11621NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri132 – 15625NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • apoptotic cell clearance Source: MGI
  • cellular lipid metabolic process Source: MGI
  • cellular response to lipopolysaccharide Source: BHF-UCL
  • cholesterol homeostasis Source: BHF-UCL
  • fatty acid biosynthetic process Source: BHF-UCL
  • insulin receptor signaling pathway Source: Ensembl
  • intracellular receptor signaling pathway Source: GOC
  • lipid homeostasis Source: BHF-UCL
  • negative regulation of cholesterol storage Source: BHF-UCL
  • negative regulation of inflammatory response Source: BHF-UCL
  • negative regulation of lipid transport Source: MGI
  • negative regulation of macrophage activation Source: BHF-UCL
  • negative regulation of pancreatic juice secretion Source: BHF-UCL
  • negative regulation of pinocytosis Source: MGI
  • negative regulation of proteolysis Source: BHF-UCL
  • negative regulation of secretion of lysosomal enzymes Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of cellular protein metabolic process Source: MGI
  • positive regulation of cholesterol efflux Source: BHF-UCL
  • positive regulation of cholesterol homeostasis Source: MGI
  • positive regulation of cholesterol transport Source: MGI
  • positive regulation of fatty acid biosynthetic process Source: MGI
  • positive regulation of lipoprotein lipase activity Source: MGI
  • positive regulation of receptor biosynthetic process Source: MGI
  • positive regulation of toll-like receptor 4 signaling pathway Source: MGI
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of triglyceride biosynthetic process Source: MGI
  • regulation of cholesterol homeostasis Source: UniProtKB
  • regulation of transcription, DNA-templated Source: MGI
  • response to progesterone Source: MGI
  • sterol homeostasis Source: BHF-UCL
  • transcription from RNA polymerase II promoter Source: GOC
  • triglyceride homeostasis Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_276696. Nuclear Receptor transcription pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Oxysterols receptor LXR-alpha
Alternative name(s):
Liver X receptor alpha
Nuclear receptor subfamily 1 group H member 3
Gene namesi
Name:Nr1h3
Synonyms:Lxra
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1352462. Nr1h3.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  • cytoplasm Source: Ensembl
  • nuclear chromatin Source: MGI
  • nucleus Source: MGI
  • receptor complex Source: MGI
  • RNA polymerase II transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 445445Oxysterols receptor LXR-alphaPRO_0000053536Add
BLAST

Proteomic databases

MaxQBiQ9Z0Y9.
PRIDEiQ9Z0Y9.

PTM databases

PhosphoSiteiQ9Z0Y9.

Expressioni

Gene expression databases

BgeeiQ9Z0Y9.
CleanExiMM_NR1H3.
ExpressionAtlasiQ9Z0Y9. baseline and differential.
GenevisibleiQ9Z0Y9. MM.

Interactioni

Subunit structurei

Heterodimer of LXRA and RXR. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with SIRT1 and this interaction is inhibited by CCAR2 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
SIRT1Q96EB62EBI-5276764,EBI-1802965From a different organism.

Protein-protein interaction databases

BioGridi204449. 6 interactions.
IntActiQ9Z0Y9. 2 interactions.
STRINGi10090.ENSMUSP00000002177.

Structurei

Secondary structure

1
445
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi206 – 22722Combined sources
Helixi228 – 2325Combined sources
Helixi245 – 27228Combined sources
Turni274 – 2785Combined sources
Helixi281 – 30121Combined sources
Turni306 – 3094Combined sources
Beta strandi310 – 3134Combined sources
Turni314 – 3163Combined sources
Beta strandi317 – 3193Combined sources
Helixi321 – 3255Combined sources
Turni326 – 3283Combined sources
Helixi331 – 34717Combined sources
Helixi351 – 36212Combined sources
Helixi373 – 39422Combined sources
Helixi401 – 42828Combined sources
Helixi435 – 4417Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2ACLX-ray2.80B/D/F/H203-445[»]
3FALX-ray2.36B/D200-445[»]
3FC6X-ray2.06B/D200-445[»]
ProteinModelPortaliQ9Z0Y9.
SMRiQ9Z0Y9. Positions 83-443.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Z0Y9.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 9494Transactivation AF-1; required for ligand-independent transactivation functionBy similarityAdd
BLAST
Regioni203 – 445243Transactivation AF-2; required for ligand-dependent transactivation function; mediates interaction with CCAR2By similarityAdd
BLAST
Regioni213 – 432220Ligand-bindingSequence AnalysisAdd
BLAST

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri96 – 11621NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri132 – 15625NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG285805.
GeneTreeiENSGT00780000121834.
HOGENOMiHOG000220845.
HOVERGENiHBG108655.
InParanoidiQ9Z0Y9.
KOiK08536.
OMAiCILREEA.
OrthoDBiEOG7DC25S.
TreeFamiTF352167.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR023257. Liver_X_rcpt.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR02034. LIVERXRECPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z0Y9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLWLEASMP DVSPDSATEL WKTEPQDAGD QGGNTCILRE EARMPQSTGV
60 70 80 90 100
ALGIGLESAE PTALLPRAET LPEPTELRPQ KRKKGPAPKM LGNELCSVCG
110 120 130 140 150
DKASGFHYNV LSCEGCKGFF RRSVIKGARY VCHSGGHCPM DTYMRRKCQE
160 170 180 190 200
CRLRKCRQAG MREECVLSEE QIRLKKLKRQ EEEQAQATSV SPRVSSPPQV
210 220 230 240 250
LPQLSPEQLG MIEKLVAAQQ QCNRRSFSDR LRVTPWPIAP DPQSREARQQ
260 270 280 290 300
RFAHFTELAI VSVQEIVDFA KQLPGFLQLS REDQIALLKT SAIEVMLLET
310 320 330 340 350
SRRYNPGSES ITFLKDFSYN REDFAKAGLQ VEFINPIFEF SRAMNELQLN
360 370 380 390 400
DAEFALLIAI SIFSADRPNV QDQLQVERLQ HTYVEALHAY VSINHPHDPL
410 420 430 440
MFPRMLMKLV SLRTLSSVHS EQVFALRLQD KKLPPLLSEI WDVHE
Length:445
Mass (Da):50,418
Last modified:July 27, 2011 - v3
Checksum:i1A426DF38D935731
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti399 – 3991P → R in CAB51952 (PubMed:10675617).Curated
Sequence conflicti399 – 3991P → R in CAB51923 (PubMed:10675617).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ132599, AJ132600 Genomic DNA. Translation: CAB51952.1.
AJ132601 mRNA. Translation: CAB51923.1.
AF085745 mRNA. Translation: AAD16050.1.
AL691450 Genomic DNA. No translation available.
CCDSiCCDS16426.1.
RefSeqiNP_001171201.1. NM_001177730.1.
NP_038867.2. NM_013839.4.
XP_006499229.1. XM_006499166.2.
XP_006499230.1. XM_006499167.2.
XP_006499231.1. XM_006499168.2.
UniGeneiMm.22690.

Genome annotation databases

EnsembliENSMUST00000002177; ENSMUSP00000002177; ENSMUSG00000002108.
ENSMUST00000111354; ENSMUSP00000106986; ENSMUSG00000002108.
ENSMUST00000111356; ENSMUSP00000106988; ENSMUSG00000002108.
GeneIDi22259.
KEGGimmu:22259.
UCSCiuc008kvc.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ132599, AJ132600 Genomic DNA. Translation: CAB51952.1.
AJ132601 mRNA. Translation: CAB51923.1.
AF085745 mRNA. Translation: AAD16050.1.
AL691450 Genomic DNA. No translation available.
CCDSiCCDS16426.1.
RefSeqiNP_001171201.1. NM_001177730.1.
NP_038867.2. NM_013839.4.
XP_006499229.1. XM_006499166.2.
XP_006499230.1. XM_006499167.2.
XP_006499231.1. XM_006499168.2.
UniGeneiMm.22690.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2ACLX-ray2.80B/D/F/H203-445[»]
3FALX-ray2.36B/D200-445[»]
3FC6X-ray2.06B/D200-445[»]
ProteinModelPortaliQ9Z0Y9.
SMRiQ9Z0Y9. Positions 83-443.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204449. 6 interactions.
IntActiQ9Z0Y9. 2 interactions.
STRINGi10090.ENSMUSP00000002177.

Chemistry

ChEMBLiCHEMBL2189152.

PTM databases

PhosphoSiteiQ9Z0Y9.

Proteomic databases

MaxQBiQ9Z0Y9.
PRIDEiQ9Z0Y9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000002177; ENSMUSP00000002177; ENSMUSG00000002108.
ENSMUST00000111354; ENSMUSP00000106986; ENSMUSG00000002108.
ENSMUST00000111356; ENSMUSP00000106988; ENSMUSG00000002108.
GeneIDi22259.
KEGGimmu:22259.
UCSCiuc008kvc.2. mouse.

Organism-specific databases

CTDi10062.
MGIiMGI:1352462. Nr1h3.

Phylogenomic databases

eggNOGiNOG285805.
GeneTreeiENSGT00780000121834.
HOGENOMiHOG000220845.
HOVERGENiHBG108655.
InParanoidiQ9Z0Y9.
KOiK08536.
OMAiCILREEA.
OrthoDBiEOG7DC25S.
TreeFamiTF352167.

Enzyme and pathway databases

ReactomeiREACT_276696. Nuclear Receptor transcription pathway.

Miscellaneous databases

EvolutionaryTraceiQ9Z0Y9.
NextBioi302349.
PROiQ9Z0Y9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Z0Y9.
CleanExiMM_NR1H3.
ExpressionAtlasiQ9Z0Y9. baseline and differential.
GenevisibleiQ9Z0Y9. MM.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR023257. Liver_X_rcpt.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR02034. LIVERXRECPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structural characterisation of the mouse nuclear oxysterol receptor genes LXRalpha and LXRbeta."
    Alberti S., Steffensen K.R., Gustafsson J.-A.
    Gene 243:93-103(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    Strain: 129/SvJ.
    Tissue: Liver.
  2. "LXRalpha functions as a cAMP-responsive transcriptional regulator of gene expression."
    Tamura K., Chen Y.E., Horiuchi M., Chen Q., Daviet L., Yang Z., Lopez-Ilasaca M., Mu H., Pratt R.E., Dzau V.J.
    Proc. Natl. Acad. Sci. U.S.A. 97:8513-8518(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "Identification of oxysterol 7alpha-hydroxylase (Cyp7b1) as a novel retinoid-related orphan receptor alpha (RORalpha) (NR1F1) target gene and a functional cross-talk between RORalpha and liver X receptor (NR1H3)."
    Wada T., Kang H.S., Angers M., Gong H., Bhatia S., Khadem S., Ren S., Ellis E., Strom S.C., Jetten A.M., Xie W.
    Mol. Pharmacol. 73:891-899(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN METABOLISM REGULATION.
  5. "LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor."
    Zelcer N., Hong C., Boyadjian R., Tontonoz P.
    Science 325:100-104(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2."
    Hong C., Duit S., Jalonen P., Out R., Scheer L., Sorrentino V., Boyadjian R., Rodenburg K.W., Foley E., Korhonen L., Lindholm D., Nimpf J., van Berkel T.J., Tontonoz P., Zelcer N.
    J. Biol. Chem. 285:19720-19726(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiNR1H3_MOUSE
AccessioniPrimary (citable) accession number: Q9Z0Y9
Secondary accession number(s): Q9QUH7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: July 22, 2015
This is version 138 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.