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Protein

Oxysterols receptor LXR-alpha

Gene

NR1H3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:19481530, PubMed:25661920). 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 (By similarity). LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides (By similarity). Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (PubMed:19481530). Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity).By similarity2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi95 – 170Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri98 – 118NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri134 – 158NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • cholesterol binding Source: BHF-UCL
  • DNA binding Source: ProtInc
  • nuclear receptor activity Source: ProtInc
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • steroid hormone receptor activity Source: InterPro
  • sterol response element binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • transcription regulatory region DNA binding Source: BHF-UCL
  • zinc ion binding Source: InterPro

GO - Biological processi

  • apoptotic cell clearance Source: UniProtKB
  • cellular response to lipopolysaccharide Source: BHF-UCL
  • cholesterol homeostasis 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 interferon-gamma-mediated signaling pathway Source: BHF-UCL
  • negative regulation of lipid transport Source: BHF-UCL
  • negative regulation of macrophage activation Source: BHF-UCL
  • negative regulation of macrophage derived foam cell differentiation Source: BHF-UCL
  • negative regulation of pancreatic juice secretion Source: BHF-UCL
  • negative regulation of pinocytosis Source: BHF-UCL
  • negative regulation of secretion of lysosomal enzymes Source: BHF-UCL
  • negative regulation of transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of cellular protein metabolic process Source: BHF-UCL
  • positive regulation of cholesterol efflux Source: UniProtKB
  • positive regulation of cholesterol transport Source: BHF-UCL
  • positive regulation of fatty acid biosynthetic process Source: BHF-UCL
  • positive regulation of lipoprotein lipase activity Source: BHF-UCL
  • positive regulation of receptor biosynthetic process Source: BHF-UCL
  • positive regulation of toll-like receptor 4 signaling pathway Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • positive regulation of triglyceride biosynthetic process Source: BHF-UCL
  • regulation of circadian rhythm Source: BHF-UCL
  • regulation of ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
  • response to progesterone Source: BHF-UCL
  • sterol homeostasis Source: BHF-UCL
  • transcription initiation from RNA polymerase II promoter Source: Reactome
  • triglyceride homeostasis Source: BHF-UCL

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-1368082 RORA activates gene expression
R-HSA-1989781 PPARA activates gene expression
R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-8866427 VLDLR internalisation and degradation
SignaLinkiQ13133
SIGNORiQ13133

Chemistry databases

SwissLipidsiSLP:000000836

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000025434.18
HGNCiHGNC:7966 NR1H3
MIMi602423 gene
neXtProtiNX_Q13133

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi268 – 273IVDFAK → EVDFAE: Abolishes interaction with NCOA2 without affecting interaction with GPS2; when associated with 438-A-A-439. 1 Publication6
Mutagenesisi438 – 439LL → AA: Abolishes interaction with NCOA2 without affecting interaction with GPS2; when associated with 268-A--A-273. 1 Publication2

Organism-specific databases

DisGeNETi10062
MalaCardsiNR1H3
OpenTargetsiENSG00000025434
PharmGKBiPA31751

Chemistry databases

ChEMBLiCHEMBL2808
GuidetoPHARMACOLOGYi602

Polymorphism and mutation databases

BioMutaiNR1H3
DMDMi23503089

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535351 – 447Oxysterols receptor LXR-alphaAdd BLAST447

Proteomic databases

MaxQBiQ13133
PaxDbiQ13133
PeptideAtlasiQ13133
PRIDEiQ13133
ProteomicsDBi59182
59183 [Q13133-2]

PTM databases

iPTMnetiQ13133
PhosphoSitePlusiQ13133

Expressioni

Tissue specificityi

Visceral organs specific expression. Strong expression was found in liver, kidney and intestine followed by spleen and to a lesser extent the adrenals.

Inductioni

By 9-cis retinoic acid (9CRA).

Gene expression databases

BgeeiENSG00000025434
CleanExiHS_NR1H3
ExpressionAtlasiQ13133 baseline and differential
GenevisibleiQ13133 HS

Organism-specific databases

HPAiCAB037109
HPA036443

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 (PubMed:25661920). Interacts with GPS2 (PubMed:19481530).2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi115373, 44 interactors
ComplexPortaliCPX-632 RXRalpha-LXRalpha nuclear hormone receptor complex
CPX-716 RXRbeta-LXRalpha nuclear hormone receptor complex
IntActiQ13133, 25 interactors
MINTiQ13133
STRINGi9606.ENSP00000387946

Chemistry databases

BindingDBiQ13133

Structurei

Secondary structure

1447
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi208 – 220Combined sources13
Helixi229 – 233Combined sources5
Helixi247 – 272Combined sources26
Helixi278 – 280Combined sources3
Helixi283 – 304Combined sources22
Turni308 – 311Combined sources4
Beta strandi312 – 315Combined sources4
Turni316 – 318Combined sources3
Beta strandi319 – 321Combined sources3
Helixi323 – 328Combined sources6
Helixi333 – 349Combined sources17
Helixi353 – 364Combined sources12
Beta strandi369 – 371Combined sources3
Helixi375 – 396Combined sources22
Helixi403 – 430Combined sources28
Helixi437 – 443Combined sources7

3D structure databases

ProteinModelPortaliQ13133
SMRiQ13133
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13133

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini209 – 447NR LBDPROSITE-ProRule annotationAdd BLAST239

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 96Transactivation AF-1; required for ligand-independent transactivation function1 PublicationAdd BLAST96
Regioni205 – 447Transactivation AF-2; required for ligand-dependent transactivation function; mediates interaction with CCAR21 PublicationAdd BLAST243

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri98 – 118NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri134 – 158NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00870000136372
HOGENOMiHOG000220845
HOVERGENiHBG108655
InParanoidiQ13133
KOiK08536
PhylomeDBiQ13133
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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13133-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSLWLGAPVP DIPPDSAVEL WKPGAQDASS QAQGGSSCIL REEARMPHSA
60 70 80 90 100
GGTAGVGLEA AEPTALLTRA EPPSEPTEIR PQKRKKGPAP KMLGNELCSV
110 120 130 140 150
CGDKASGFHY NVLSCEGCKG FFRRSVIKGA HYICHSGGHC PMDTYMRRKC
160 170 180 190 200
QECRLRKCRQ AGMREECVLS EEQIRLKKLK RQEEEQAHAT SLPPRASSPP
210 220 230 240 250
QILPQLSPEQ LGMIEKLVAA QQQCNRRSFS DRLRVTPWPM APDPHSREAR
260 270 280 290 300
QQRFAHFTEL AIVSVQEIVD FAKQLPGFLQ LSREDQIALL KTSAIEVMLL
310 320 330 340 350
ETSRRYNPGS ESITFLKDFS YNREDFAKAG LQVEFINPIF EFSRAMNELQ
360 370 380 390 400
LNDAEFALLI AISIFSADRP NVQDQLQVER LQHTYVEALH AYVSIHHPHD
410 420 430 440
RLMFPRMLMK LVSLRTLSSV HSEQVFALRL QDKKLPPLLS EIWDVHE
Length:447
Mass (Da):50,396
Last modified:September 19, 2002 - v2
Checksum:i0D27B237440F8C9C
GO
Isoform 2 (identifier: Q13133-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     237-296: Missing.

Note: No experimental confirmation available.
Show »
Length:387
Mass (Da):43,555
Checksum:i9C96CF2BBE66403C
GO
Isoform 3 (identifier: Q13133-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-45: Missing.

Note: No experimental confirmation available.
Show »
Length:402
Mass (Da):45,692
Checksum:i78EAE53CFB2358E7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti196A → R in AAA85856 (PubMed:7744246).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05058052G → V. Corresponds to variant dbSNP:rs41481445Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0449601 – 45Missing in isoform 3. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_003664237 – 296Missing in isoform 2. 1 PublicationAdd BLAST60

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U22662 mRNA Translation: AAA85856.1
AK290614 mRNA Translation: BAF83303.1
AC018410 Genomic DNA No translation available.
CH471064 Genomic DNA Translation: EAW67949.1
CH471064 Genomic DNA Translation: EAW67942.1
CH471064 Genomic DNA Translation: EAW67943.1
CH471064 Genomic DNA Translation: EAW67944.1
CH471064 Genomic DNA Translation: EAW67947.1
CH471064 Genomic DNA Translation: EAW67948.1
BC008819 mRNA Translation: AAH08819.1
BC041172 mRNA Translation: AAH41172.1
CCDSiCCDS44584.1 [Q13133-2]
CCDS44585.1 [Q13133-3]
CCDS7929.1 [Q13133-1]
PIRiI38975
RefSeqiNP_001123573.1, NM_001130101.2 [Q13133-2]
NP_001123574.1, NM_001130102.2 [Q13133-3]
NP_005684.2, NM_005693.3 [Q13133-1]
XP_005252762.1, XM_005252705.1 [Q13133-1]
XP_005252763.1, XM_005252706.1 [Q13133-1]
XP_005252764.1, XM_005252707.4 [Q13133-1]
XP_005252766.1, XM_005252709.1 [Q13133-3]
XP_005252767.1, XM_005252710.1 [Q13133-3]
XP_005252770.1, XM_005252713.3 [Q13133-2]
XP_006718175.1, XM_006718112.1 [Q13133-1]
XP_006718176.1, XM_006718113.1 [Q13133-1]
XP_006718178.1, XM_006718115.1 [Q13133-3]
XP_006718179.1, XM_006718116.1 [Q13133-3]
XP_011518107.1, XM_011519805.2 [Q13133-1]
XP_016872547.1, XM_017017058.1 [Q13133-3]
UniGeneiHs.438863

Genome annotation databases

EnsembliENST00000395397; ENSP00000378793; ENSG00000025434 [Q13133-3]
ENST00000405853; ENSP00000384745; ENSG00000025434 [Q13133-2]
ENST00000407404; ENSP00000385801; ENSG00000025434 [Q13133-2]
ENST00000441012; ENSP00000387946; ENSG00000025434 [Q13133-1]
ENST00000467728; ENSP00000420656; ENSG00000025434 [Q13133-1]
GeneIDi10062
KEGGihsa:10062
UCSCiuc001nek.4 human [Q13133-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNR1H3_HUMAN
AccessioniPrimary (citable) accession number: Q13133
Secondary accession number(s): A8K3J9
, D3DQR1, Q8IW13, Q96H87
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 19, 2002
Last modified: July 18, 2018
This is version 193 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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