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Protein

Oxysterols receptor LXR-beta

Gene

NR1H2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Nuclear receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920).By similarity1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi84 – 161Nuclear receptorPROSITE-ProRule annotationAdd BLAST78
Zinc fingeri87 – 107NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri125 – 149NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

  • cellular lipid metabolic process Source: Ensembl
  • cholesterol homeostasis Source: Ensembl
  • negative regulation of cholesterol storage 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 derived foam cell differentiation Source: BHF-UCL
  • negative regulation of pinocytosis Source: BHF-UCL
  • negative regulation of proteolysis Source: Ensembl
  • negative regulation of transcription, DNA-templated Source: HGNC
  • negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • positive regulation of cellular protein metabolic process Source: BHF-UCL
  • positive regulation of cholesterol efflux Source: BHF-UCL
  • positive regulation of cholesterol transport Source: BHF-UCL
  • positive regulation of fatty acid biosynthetic process Source: BHF-UCL
  • positive regulation of high-density lipoprotein particle assembly Source: Ensembl
  • positive regulation of lipid storage Source: Ensembl
  • positive regulation of lipoprotein lipase activity Source: BHF-UCL
  • positive regulation of pancreatic juice secretion Source: Ensembl
  • positive regulation of secretion of lysosomal enzymes Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of triglyceride biosynthetic process Source: BHF-UCL
  • regulation of cholesterol homeostasis Source: UniProtKB
  • retinoic acid receptor signaling pathway Source: Ensembl
  • transcription initiation from RNA polymerase II promoter Source: Reactome
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

BioCyciZFISH:ENSG00000131408-MONOMER.
ReactomeiR-HSA-383280. Nuclear Receptor transcription pathway.
R-HSA-8866427. VLDLR internalisation and degradation.
SignaLinkiP55055.
SIGNORiP55055.

Chemistry databases

SwissLipidsiSLP:000001551.

Names & Taxonomyi

Protein namesi
Recommended name:
Oxysterols receptor LXR-beta
Alternative name(s):
Liver X receptor beta
Nuclear receptor NER
Nuclear receptor subfamily 1 group H member 2
Ubiquitously-expressed nuclear receptor
Gene namesi
Name:NR1H2
Synonyms:LXRB, NER, UNR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:7965. NR1H2.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  • cytoplasm Source: HGNC
  • nucleoplasm Source: Reactome
  • nucleus Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi7376.
OpenTargetsiENSG00000131408.
PharmGKBiPA31750.

Chemistry databases

ChEMBLiCHEMBL4093.
GuidetoPHARMACOLOGYi601.

Polymorphism and mutation databases

BioMutaiNR1H2.
DMDMi296439251.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535321 – 460Oxysterols receptor LXR-betaAdd BLAST460

Proteomic databases

MaxQBiP55055.
PaxDbiP55055.
PeptideAtlasiP55055.
PRIDEiP55055.

PTM databases

iPTMnetiP55055.
PhosphoSitePlusiP55055.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000131408.
CleanExiHS_NR1H2.
ExpressionAtlasiP55055. baseline and differential.
GenevisibleiP55055. HS.

Organism-specific databases

HPAiHPA056838.
HPA070212.

Interactioni

Subunit structurei

Forms a heterodimer with RXR. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ABCA1O954772EBI-745354,EBI-784112
MDFIQ997503EBI-745354,EBI-724076
NCOR1O753766EBI-745354,EBI-347233

GO - Molecular functioni

  • apolipoprotein A-I receptor binding Source: BHF-UCL
  • ATPase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi113222. 57 interactors.
DIPiDIP-53004N.
IntActiP55055. 31 interactors.
MINTiMINT-1444220.
STRINGi9606.ENSP00000253727.

Chemistry databases

BindingDBiP55055.

Structurei

Secondary structure

1460
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi88 – 90Combined sources3
Beta strandi99 – 103Combined sources5
Helixi105 – 116Combined sources12
Helixi137 – 139Combined sources3
Helixi142 – 151Combined sources10
Helixi162 – 165Combined sources4
Turni167 – 169Combined sources3
Helixi170 – 173Combined sources4
Turni176 – 178Combined sources3
Beta strandi183 – 185Combined sources3
Beta strandi212 – 214Combined sources3
Helixi221 – 241Combined sources21
Helixi242 – 244Combined sources3
Turni245 – 247Combined sources3
Helixi260 – 286Combined sources27
Helixi291 – 293Combined sources3
Helixi296 – 317Combined sources22
Beta strandi318 – 320Combined sources3
Turni321 – 324Combined sources4
Beta strandi325 – 328Combined sources4
Turni329 – 331Combined sources3
Beta strandi332 – 334Combined sources3
Helixi336 – 340Combined sources5
Turni341 – 343Combined sources3
Helixi349 – 360Combined sources12
Turni361 – 363Combined sources3
Helixi366 – 377Combined sources12
Helixi388 – 409Combined sources22
Turni411 – 413Combined sources3
Helixi416 – 434Combined sources19
Beta strandi444 – 446Combined sources3
Helixi450 – 455Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P8DX-ray2.80A/B213-460[»]
1PQ6X-ray2.40A/B/C/D212-460[»]
1PQ9X-ray2.10A/B/C/D212-460[»]
1PQCX-ray2.80A/B/C/D212-460[»]
1UPVX-ray2.10A208-460[»]
1UPWX-ray2.40A208-460[»]
3KFCX-ray2.40A/B/C/D212-460[»]
3L0EX-ray2.30A212-460[»]
4DK7X-ray2.45A/C218-460[»]
4DK8X-ray2.75A/C218-460[»]
4NQAX-ray3.10B/I72-460[»]
4RAKX-ray2.04A/B213-460[»]
5HJPX-ray2.60B/D216-460[»]
5I4VX-ray2.61A/E210-460[»]
5KYAX-ray2.60A/E210-460[»]
5KYJX-ray2.80A/E210-460[»]
ProteinModelPortaliP55055.
SMRiP55055.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55055.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 85Transactivation AF-1; required for ligand-independent transactivation function1 PublicationAdd BLAST85
Regioni219 – 460Transactivation AF-2; required for ligand-dependent transactivation function; mediates interaction with CCAR21 PublicationAdd BLAST242
Regioni230 – 460Ligand-bindingSequence analysisAdd BLAST231

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi190 – 195Poly-Ser6

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri87 – 107NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri125 – 149NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00850000132242.
HOGENOMiHOG000220845.
HOVERGENiHBG108655.
InParanoidiP55055.
KOiK08535.
OMAiRRYACRG.
OrthoDBiEOG091G0I4P.
PhylomeDBiP55055.
TreeFamiTF352167.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR023257. Liver_X_rcpt.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P55055-1) [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
MSSPTTSSLD TPLPGNGPPQ PGAPSSSPTV KEEGPEPWPG GPDPDVPGTD
60 70 80 90 100
EASSACSTDW VIPDPEEEPE RKRKKGPAPK MLGHELCRVC GDKASGFHYN
110 120 130 140 150
VLSCEGCKGF FRRSVVRGGA RRYACRGGGT CQMDAFMRRK CQQCRLRKCK
160 170 180 190 200
EAGMREQCVL SEEQIRKKKI RKQQQESQSQ SQSPVGPQGS SSSASGPGAS
210 220 230 240 250
PGGSEAGSQG SGEGEGVQLT AAQELMIQQL VAAQLQCNKR SFSDQPKVTP
260 270 280 290 300
WPLGADPQSR DARQQRFAHF TELAIISVQE IVDFAKQVPG FLQLGREDQI
310 320 330 340 350
ALLKASTIEI MLLETARRYN HETECITFLK DFTYSKDDFH RAGLQVEFIN
360 370 380 390 400
PIFEFSRAMR RLGLDDAEYA LLIAINIFSA DRPNVQEPGR VEALQQPYVE
410 420 430 440 450
ALLSYTRIKR PQDQLRFPRM LMKLVSLRTL SSVHSEQVFA LRLQDKKLPP
460
LLSEIWDVHE
Length:460
Mass (Da):50,974
Last modified:May 18, 2010 - v2
Checksum:i9465A6FFB7FCFD2F
GO
Isoform 2 (identifier: P55055-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     61-158: VIPDPEEEPE...CKEAGMREQC → G

Note: No experimental confirmation.
Show »
Length:363
Mass (Da):39,920
Checksum:iE1F0B75FDA51C249
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti175Q → QQ in AAA61783 (PubMed:7926814).Curated1
Sequence conflicti175Q → QQ in BAF83544 (PubMed:14702039).Curated1
Sequence conflicti175Q → QQ in BAG60288 (PubMed:14702039).Curated1
Sequence conflicti175Q → QQ in AAH07790 (PubMed:15489334).Curated1
Sequence conflicti175Q → QQ in AAH33500 (PubMed:15489334).Curated1
Sequence conflicti175Q → QQ in AAH47750 (PubMed:15489334).Curated1
Sequence conflicti175Q → QQ in AAH74500 (PubMed:15489334).Curated1
Sequence conflicti175Q → QQ in AAA58594 (Ref. 5) Curated1
Sequence conflicti244D → G in BAG60288 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0505792S → F.Corresponds to variant rs41379547dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05378961 – 158VIPDP…MREQC → G in isoform 2. 1 PublicationAdd BLAST98

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07132 mRNA. Translation: AAA61783.1.
AK290855 mRNA. Translation: BAF83544.1.
AK297978 mRNA. Translation: BAG60288.1.
AC008655 Genomic DNA. No translation available.
BC007790 mRNA. Translation: AAH07790.1.
BC033500 mRNA. Translation: AAH33500.1.
BC047750 mRNA. Translation: AAH47750.1.
BC074500 mRNA. Translation: AAH74500.1.
U14534 mRNA. Translation: AAA58594.1.
PIRiJC4014.
RefSeqiNP_001243576.1. NM_001256647.1.
NP_009052.3. NM_007121.5.
UniGeneiHs.432976.

Genome annotation databases

EnsembliENST00000253727; ENSP00000253727; ENSG00000131408. [P55055-1]
ENST00000411902; ENSP00000396151; ENSG00000131408. [P55055-2]
ENST00000593926; ENSP00000471194; ENSG00000131408. [P55055-1]
GeneIDi7376.
KEGGihsa:7376.
UCSCiuc002psa.6. human. [P55055-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07132 mRNA. Translation: AAA61783.1.
AK290855 mRNA. Translation: BAF83544.1.
AK297978 mRNA. Translation: BAG60288.1.
AC008655 Genomic DNA. No translation available.
BC007790 mRNA. Translation: AAH07790.1.
BC033500 mRNA. Translation: AAH33500.1.
BC047750 mRNA. Translation: AAH47750.1.
BC074500 mRNA. Translation: AAH74500.1.
U14534 mRNA. Translation: AAA58594.1.
PIRiJC4014.
RefSeqiNP_001243576.1. NM_001256647.1.
NP_009052.3. NM_007121.5.
UniGeneiHs.432976.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P8DX-ray2.80A/B213-460[»]
1PQ6X-ray2.40A/B/C/D212-460[»]
1PQ9X-ray2.10A/B/C/D212-460[»]
1PQCX-ray2.80A/B/C/D212-460[»]
1UPVX-ray2.10A208-460[»]
1UPWX-ray2.40A208-460[»]
3KFCX-ray2.40A/B/C/D212-460[»]
3L0EX-ray2.30A212-460[»]
4DK7X-ray2.45A/C218-460[»]
4DK8X-ray2.75A/C218-460[»]
4NQAX-ray3.10B/I72-460[»]
4RAKX-ray2.04A/B213-460[»]
5HJPX-ray2.60B/D216-460[»]
5I4VX-ray2.61A/E210-460[»]
5KYAX-ray2.60A/E210-460[»]
5KYJX-ray2.80A/E210-460[»]
ProteinModelPortaliP55055.
SMRiP55055.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113222. 57 interactors.
DIPiDIP-53004N.
IntActiP55055. 31 interactors.
MINTiMINT-1444220.
STRINGi9606.ENSP00000253727.

Chemistry databases

BindingDBiP55055.
ChEMBLiCHEMBL4093.
GuidetoPHARMACOLOGYi601.
SwissLipidsiSLP:000001551.

PTM databases

iPTMnetiP55055.
PhosphoSitePlusiP55055.

Polymorphism and mutation databases

BioMutaiNR1H2.
DMDMi296439251.

Proteomic databases

MaxQBiP55055.
PaxDbiP55055.
PeptideAtlasiP55055.
PRIDEiP55055.

Protocols and materials databases

DNASUi7376.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000253727; ENSP00000253727; ENSG00000131408. [P55055-1]
ENST00000411902; ENSP00000396151; ENSG00000131408. [P55055-2]
ENST00000593926; ENSP00000471194; ENSG00000131408. [P55055-1]
GeneIDi7376.
KEGGihsa:7376.
UCSCiuc002psa.6. human. [P55055-1]

Organism-specific databases

CTDi7376.
DisGeNETi7376.
GeneCardsiNR1H2.
HGNCiHGNC:7965. NR1H2.
HPAiHPA056838.
HPA070212.
MIMi600380. gene.
neXtProtiNX_P55055.
OpenTargetsiENSG00000131408.
PharmGKBiPA31750.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00850000132242.
HOGENOMiHOG000220845.
HOVERGENiHBG108655.
InParanoidiP55055.
KOiK08535.
OMAiRRYACRG.
OrthoDBiEOG091G0I4P.
PhylomeDBiP55055.
TreeFamiTF352167.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000131408-MONOMER.
ReactomeiR-HSA-383280. Nuclear Receptor transcription pathway.
R-HSA-8866427. VLDLR internalisation and degradation.
SignaLinkiP55055.
SIGNORiP55055.

Miscellaneous databases

ChiTaRSiNR1H2. human.
EvolutionaryTraceiP55055.
GeneWikiiLiver_X_receptor_beta.
GenomeRNAii7376.
PROiP55055.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131408.
CleanExiHS_NR1H2.
ExpressionAtlasiP55055. baseline and differential.
GenevisibleiP55055. HS.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR023257. Liver_X_rcpt.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_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...

Entry informationi

Entry nameiNR1H2_HUMAN
AccessioniPrimary (citable) accession number: P55055
Secondary accession number(s): A8K490
, B4DNM6, E7EWA6, Q12970, Q5I0Y1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 18, 2010
Last modified: November 2, 2016
This is version 180 of the entry and version 2 of the sequence. [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 19
    Human chromosome 19: 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

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 one 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.