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Q13133 (NR1H3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Oxysterols receptor LXR-alpha
Alternative name(s):
Liver X receptor alpha
Nuclear receptor subfamily 1 group H member 3
Gene names
Name:NR1H3
Synonyms:LXRA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length447 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity.

Subunit structure

Heterodimer of LXRA and RXR.

Subcellular location

Nucleus Potential.

Tissue specificity

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

Induction

By 9-cis retinoic acid (9CRA).

Sequence similarities

Belongs to the nuclear hormone receptor family. NR1 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic cell clearance

Inferred from mutant phenotype PubMed 19628791. Source: UniProtKB

cellular lipid metabolic process

Inferred from electronic annotation. Source: Ensembl

cellular response to lipopolysaccharide

Inferred from direct assay PubMed 18511497. Source: BHF-UCL

cholesterol homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

gene expression

Traceable author statement. Source: Reactome

lipid homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of cholesterol storage

Inferred from mutant phenotype PubMed 17693624. Source: BHF-UCL

negative regulation of inflammatory response

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of interferon-gamma-mediated signaling pathway

Non-traceable author statement PubMed 21268089. Source: BHF-UCL

negative regulation of lipid transport

Inferred from mutant phenotype PubMed 17693624. Source: BHF-UCL

negative regulation of macrophage activation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of macrophage derived foam cell differentiation

Inferred by curator PubMed 17693624. Source: BHF-UCL

negative regulation of pancreatic juice secretion

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of pinocytosis

Inferred from mutant phenotype PubMed 17693624. Source: BHF-UCL

negative regulation of proteolysis

Inferred from electronic annotation. Source: Ensembl

negative regulation of secretion of lysosomal enzymes

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of cellular protein metabolic process

Inferred from mutant phenotype PubMed 17186944. Source: BHF-UCL

positive regulation of cholesterol efflux

Inferred from direct assay PubMed 16141411. Source: BHF-UCL

positive regulation of cholesterol homeostasis

Inferred from direct assay PubMed 18511497. Source: BHF-UCL

positive regulation of cholesterol transport

Inferred from direct assay PubMed 16141411. Source: BHF-UCL

positive regulation of fatty acid biosynthetic process

Inferred from mutant phenotype PubMed 17186944. Source: BHF-UCL

positive regulation of lipoprotein lipase activity

Inferred from mutant phenotype PubMed 17186944. Source: BHF-UCL

positive regulation of receptor biosynthetic process

Inferred from direct assay PubMed 18511497. Source: BHF-UCL

positive regulation of toll-like receptor 4 signaling pathway

Inferred from direct assay PubMed 18511497. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 20219900. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 19628791. Source: UniProtKB

positive regulation of triglyceride biosynthetic process

Inferred from mutant phenotype PubMed 17693624. Source: BHF-UCL

regulation of circadian rhythm

Traceable author statement PubMed 18511497. Source: BHF-UCL

response to progesterone

Inferred from direct assay PubMed 16141411. Source: BHF-UCL

sterol homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

triglyceride homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentnuclear chromatin

Inferred from direct assay PubMed 18511497. Source: BHF-UCL

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionDNA binding

Traceable author statement Ref.1. Source: ProtInc

cholesterol binding

Traceable author statement PubMed 11090131. Source: BHF-UCL

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Traceable author statement Ref.1. Source: ProtInc

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

sterol response element binding

Inferred from direct assay PubMed 19628791. Source: UniProtKB

transcription coactivator activity

Traceable author statement Ref.1. Source: ProtInc

transcription regulatory region DNA binding

Inferred from direct assay PubMed 19229075. Source: BHF-UCL

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13133-1)

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.
Isoform 2 (identifier: Q13133-2)

The sequence of this isoform differs from the canonical sequence as follows:
     237-296: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q13133-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-45: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 447447Oxysterols receptor LXR-alpha
PRO_0000053535

Regions

DNA binding95 – 17076Nuclear receptor
Zinc finger98 – 11821NR C4-type
Zinc finger134 – 15825NR C4-type
Region215 – 434220Ligand-binding Potential

Natural variations

Alternative sequence1 – 4545Missing in isoform 3.
VSP_044960
Alternative sequence237 – 29660Missing in isoform 2.
VSP_003664
Natural variant521G → V.
Corresponds to variant rs41481445 [ dbSNP | Ensembl ].
VAR_050580

Experimental info

Sequence conflict1961A → R in AAA85856. Ref.1

Secondary structure

.............................. 447
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 19, 2002. Version 2.
Checksum: 0D27B237440F8C9C

FASTA44750,396
        10         20         30         40         50         60 
MSLWLGAPVP DIPPDSAVEL WKPGAQDASS QAQGGSSCIL REEARMPHSA GGTAGVGLEA 

        70         80         90        100        110        120 
AEPTALLTRA EPPSEPTEIR PQKRKKGPAP KMLGNELCSV CGDKASGFHY NVLSCEGCKG 

       130        140        150        160        170        180 
FFRRSVIKGA HYICHSGGHC PMDTYMRRKC QECRLRKCRQ AGMREECVLS EEQIRLKKLK 

       190        200        210        220        230        240 
RQEEEQAHAT SLPPRASSPP QILPQLSPEQ LGMIEKLVAA QQQCNRRSFS DRLRVTPWPM 

       250        260        270        280        290        300 
APDPHSREAR QQRFAHFTEL AIVSVQEIVD FAKQLPGFLQ LSREDQIALL KTSAIEVMLL 

       310        320        330        340        350        360 
ETSRRYNPGS ESITFLKDFS YNREDFAKAG LQVEFINPIF EFSRAMNELQ LNDAEFALLI 

       370        380        390        400        410        420 
AISIFSADRP NVQDQLQVER LQHTYVEALH AYVSIHHPHD RLMFPRMLMK LVSLRTLSSV 

       430        440 
HSEQVFALRL QDKKLPPLLS EIWDVHE 

« Hide

Isoform 2 [UniParc].

Checksum: 9C96CF2BBE66403C
Show »

FASTA38743,555
Isoform 3 [UniParc].

Checksum: 78EAE53CFB2358E7
Show »

FASTA40245,692

References

« Hide 'large scale' references
[1]"LXR, a nuclear receptor that defines a distinct retinoid response pathway."
Willy P.J., Umesono K., Ong E.S., Evans R.M., Heyman R.A., Mangelsdorf D.J.
Genes Dev. 9:1033-1045(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Heart.
[3]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
Tissue: Brain and Placenta.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRI38975.
RefSeqNP_001123573.1. NM_001130101.2.
NP_001123574.1. NM_001130102.2.
NP_005684.2. NM_005693.3.
XP_005252762.1. XM_005252705.1.
XP_005252763.1. XM_005252706.1.
XP_005252764.1. XM_005252707.2.
XP_005252766.1. XM_005252709.1.
XP_005252767.1. XM_005252710.1.
XP_005252770.1. XM_005252713.1.
UniGeneHs.438863.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1UHLX-ray2.90B207-447[»]
3IPQX-ray2.00A182-447[»]
3IPSX-ray2.26A/B182-447[»]
3IPUX-ray2.40A/B182-447[»]
ProteinModelPortalQ13133.
SMRQ13133. Positions 96-445.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115373. 32 interactions.
IntActQ13133. 9 interactions.
MINTMINT-3027136.
STRING9606.ENSP00000342470.

Chemistry

BindingDBQ13133.
ChEMBLCHEMBL2808.
GuidetoPHARMACOLOGY602.

PTM databases

PhosphoSiteQ13133.

Polymorphism databases

DMDM23503089.

Proteomic databases

PaxDbQ13133.
PRIDEQ13133.

Protocols and materials databases

DNASU10062.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000395397; ENSP00000378793; ENSG00000025434. [Q13133-3]
ENST00000405853; ENSP00000384745; ENSG00000025434. [Q13133-2]
ENST00000407404; ENSP00000385801; ENSG00000025434. [Q13133-2]
ENST00000441012; ENSP00000387946; ENSG00000025434. [Q13133-1]
ENST00000467728; ENSP00000420656; ENSG00000025434. [Q13133-1]
GeneID10062.
KEGGhsa:10062.
UCSCuc001nek.3. human. [Q13133-1]
uc001nen.4. human. [Q13133-2]

Organism-specific databases

CTD10062.
GeneCardsGC11P047269.
HGNCHGNC:7966. NR1H3.
HPACAB037109.
HPA036443.
MIM602423. gene.
neXtProtNX_Q13133.
PharmGKBPA31751.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG285805.
HOGENOMHOG000220845.
HOVERGENHBG108655.
InParanoidQ13133.
KOK08536.
OMACILREEA.
PhylomeDBQ13133.
TreeFamTF352167.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.
SignaLinkQ13133.

Gene expression databases

ArrayExpressQ13133.
BgeeQ13133.
CleanExHS_NR1H3.
GenevestigatorQ13133.

Family and domain databases

Gene3D1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProIPR023257. 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]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR02034. LIVERXRECPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ13133.
GeneWikiLiver_X_receptor_alpha.
GenomeRNAi10062.
NextBio38029.
PROQ13133.
SOURCESearch...

Entry information

Entry nameNR1H3_HUMAN
AccessionPrimary (citable) accession number: Q13133
Secondary accession number(s): A8K3J9 expand/collapse secondary AC list , D3DQR1, Q8IW13, Q96H87
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 19, 2002
Last modified: April 16, 2014
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM