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Protein

Oxysterols receptor LXR-alpha

Gene

Nr1h3

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

Functioni

Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:18055760, PubMed:19520913, PubMed:20427281). Interaction with retinoic acid receptor (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.By similarity3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi93 – 168Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri96 – 116NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri132 – 156NR C4-typePROSITE-ProRule annotationAdd BLAST25

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
  • 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 by RNA polymerase II 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 by RNA polymerase II 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
  • triglyceride homeostasis Source: BHF-UCL

Keywordsi

Molecular functionActivator, DNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-383280 Nuclear Receptor transcription pathway
R-MMU-8866427 VLDLR internalisation and degradation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1352462 Nr1h3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2189152
GuidetoPHARMACOLOGYi602

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535361 – 445Oxysterols receptor LXR-alphaAdd BLAST445

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei191PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9Z0Y9
PaxDbiQ9Z0Y9
PRIDEiQ9Z0Y9

PTM databases

iPTMnetiQ9Z0Y9
PhosphoSitePlusiQ9Z0Y9

Expressioni

Gene expression databases

BgeeiENSMUSG00000002108
CleanExiMM_NR1H3
ExpressionAtlasiQ9Z0Y9 baseline and differential
GenevisibleiQ9Z0Y9 MM

Interactioni

Subunit structurei

Heterodimer of NR1H3 and RXR (retinoic acid receptor). 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

Show more details

Protein-protein interaction databases

BioGridi204449, 6 interactors
DIPiDIP-62095N
IntActiQ9Z0Y9, 5 interactors
MINTiQ9Z0Y9
STRINGi10090.ENSMUSP00000002177

Structurei

Secondary structure

1445
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi206 – 227Combined sources22
Helixi228 – 232Combined sources5
Helixi245 – 272Combined sources28
Turni274 – 278Combined sources5
Helixi281 – 301Combined sources21
Turni306 – 309Combined sources4
Beta strandi310 – 313Combined sources4
Turni314 – 316Combined sources3
Beta strandi317 – 319Combined sources3
Helixi321 – 325Combined sources5
Turni326 – 328Combined sources3
Helixi331 – 347Combined sources17
Helixi351 – 362Combined sources12
Helixi373 – 394Combined sources22
Helixi401 – 428Combined sources28
Helixi435 – 441Combined sources7

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiQ9Z0Y9

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini207 – 445NR LBDPROSITE-ProRule annotationAdd BLAST239

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 94Transactivation AF-1; required for ligand-independent transactivation functionBy similarityAdd BLAST94
Regioni203 – 445Transactivation AF-2; required for ligand-dependent transactivation function; mediates interaction with CCAR2By similarityAdd BLAST243

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri96 – 116NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri132 – 156NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00870000136372
HOGENOMiHOG000220845
HOVERGENiHBG108655
InParanoidiQ9Z0Y9
KOiK08536
OMAiVELWEPD
OrthoDBiEOG091G0I4P
TreeFamiTF352167

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR023257 Liver_X_rcpt
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR02034 LIVERXRECPTR
PR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti399P → R in CAB51952 (PubMed:10675617).Curated1
Sequence conflicti399P → R in CAB51923 (PubMed:10675617).Curated1

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_006499168.3
UniGeneiMm.22690

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiNR1H3_MOUSE
AccessioniPrimary (citable) accession number: Q9Z0Y9
Secondary accession number(s): Q9QUH7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: April 25, 2018
This is version 161 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health