Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Oxysterols receptor LXR-beta

Gene

NR1H2

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:25661920). 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). Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957).By similarity2 Publications

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: UniProtKB
  • 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 by RNA polymerase II 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 by RNA polymerase II Source: UniProtKB
  • positive regulation of triglyceride biosynthetic process Source: BHF-UCL
  • retinoic acid receptor signaling pathway Source: Ensembl
  • transcription initiation from RNA polymerase II promoter Source: Reactome

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
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

EuPathDBiHostDB:ENSG00000131408.13
HGNCiHGNC:7965 NR1H2
MIMi600380 gene
neXtProtiNX_P55055

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
Mutagenesisi409K → R: Impaired ability to act as an anti-inflammatory role during the hepatic acute phase response; when associated with R-447. 1 Publication1
Mutagenesisi447K → R: Impaired ability to act as an anti-inflammatory role during the hepatic acute phase response; when associated with R-409. 1 Publication1

Organism-specific databases

DisGeNETi7376
OpenTargetsiENSG00000131408
PharmGKBiPA31750

Chemistry databases

ChEMBLiCHEMBL4093
DrugBankiDB03848 Benzenesulfonyl
GuidetoPHARMACOLOGYi601

Polymorphism and mutation databases

BioMutaiNR1H2
DMDMi296439251

PTM / Processingi

Molecule processing

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

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki409Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)1 Publication
Cross-linki447Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)1 Publication

Post-translational modificationi

Sumoylated by SUMO2 at Lys-409 and Lys-447 during the hepatic acute phase response, leading to promote interaction with GPS2 and prevent N-Cor corepressor complex dissociation.1 Publication

Keywords - PTMi

Isopeptide bond, Ubl conjugation

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 (PubMed:25661920). Interacts (when sumoylated) with GPS2; interaction with GPS2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (PubMed:20159957).3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi113222, 58 interactors
DIPiDIP-53004N
IntActiP55055, 38 interactors
MINTiP55055
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[»]
5JY3X-ray2.40A/B/C/D213-460[»]
5KYAX-ray2.60A/E210-460[»]
5KYJX-ray2.80A/E210-460[»]
ProteinModelPortaliP55055
SMRiP55055
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55055

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini222 – 460NR LBDPROSITE-ProRule annotationAdd BLAST239

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

Compositional bias

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

Sequence similaritiesi

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
GeneTreeiENSGT00870000136372
HOGENOMiHOG000220845
HOVERGENiHBG108655
InParanoidiP55055
KOiK08535
OMAiRRYACRG
OrthoDBiEOG091G0I4P
PhylomeDBiP55055
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 (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 dbSNP:rs41379547Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiNR1H2_HUMAN
AccessioniPrimary (citable) accession number: P55055
Secondary accession number(s): A8K490
, B4DNM6, E7EWA6, Q12970, Q5I0Y1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 18, 2010
Last modified: May 23, 2018
This is version 194 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 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health