Q9Z0Y9 · NR1H3_MOUSE
- ProteinOxysterols receptor LXR-alpha
- GeneNr1h3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids445 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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 similarity).
Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (PubMed:25806685, PubMed:28846071).
Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (PubMed:25806685).
Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (PubMed:24206663).
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 similarity).
Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (PubMed:25806685, PubMed:28846071).
Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (PubMed:25806685).
Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (PubMed:24206663).
Features
Showing features for dna binding.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
DNA binding | 93-168 | Nuclear receptor | ||||
Sequence: NELCSVCGDKASGFHYNVLSCEGCKGFFRRSVIKGARYVCHSGGHCPMDTYMRRKCQECRLRKCRQAGMREECVLS |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameOxysterols receptor LXR-alpha
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9Z0Y9
- Secondary accessions
Proteomes
Organism-specific databases
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 12 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000053536 | 1-445 | Oxysterols receptor LXR-alpha | |||
Sequence: MSLWLEASMPDVSPDSATELWKTEPQDAGDQGGNTCILREEARMPQSTGVALGIGLESAEPTALLPRAETLPEPTELRPQKRKKGPAPKMLGNELCSVCGDKASGFHYNVLSCEGCKGFFRRSVIKGARYVCHSGGHCPMDTYMRRKCQECRLRKCRQAGMREECVLSEEQIRLKKLKRQEEEQAQATSVSPRVSSPPQVLPQLSPEQLGMIEKLVAAQQQCNRRSFSDRLRVTPWPIAPDPQSREARQQRFAHFTELAIVSVQEIVDFAKQLPGFLQLSREDQIALLKTSAIEVMLLETSRRYNPGSESITFLKDFSYNREDFAKAGLQVEFINPIFEFSRAMNELQLNDAEFALLIAISIFSADRPNVQDQLQVERLQHTYVEALHAYVSINHPHDPLMFPRMLMKLVSLRTLSSVHSEQVFALRLQDKKLPPLLSEIWDVHE | ||||||
Modified residue | 191 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Ubiquitinated (PubMed:27383786).
Ubiquitination by UBR5 leads to its degradation: UBR5 specifically recognizes and binds ligand-bound NR1H3 when it is not associated with coactivators (NCOAs) (By similarity).
In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (By similarity).
Ubiquitination by UBR5 leads to its degradation: UBR5 specifically recognizes and binds ligand-bound NR1H3 when it is not associated with coactivators (NCOAs) (By similarity).
In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Z0Y9 | Men1 O88559 | 3 | EBI-5276764, EBI-3990176 | |
XENO | Q9Z0Y9 | SIRT1 Q96EB6 | 2 | EBI-5276764, EBI-1802965 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, zinc finger, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-34 | Disordered | ||||
Sequence: MSLWLEASMPDVSPDSATELWKTEPQDAGDQGGN | ||||||
Region | 1-94 | Transactivation AF-1; required for ligand-independent transactivation function | ||||
Sequence: MSLWLEASMPDVSPDSATELWKTEPQDAGDQGGNTCILREEARMPQSTGVALGIGLESAEPTALLPRAETLPEPTELRPQKRKKGPAPKMLGNE | ||||||
Region | 63-86 | Disordered | ||||
Sequence: ALLPRAETLPEPTELRPQKRKKGP | ||||||
Zinc finger | 96-116 | NR C4-type | ||||
Sequence: CSVCGDKASGFHYNVLSCEGC | ||||||
Zinc finger | 132-156 | NR C4-type | ||||
Sequence: CHSGGHCPMDTYMRRKCQECRLRKC | ||||||
Region | 203-445 | Transactivation AF-2; required for ligand-dependent transactivation function; mediates interaction with CCAR2 | ||||
Sequence: QLSPEQLGMIEKLVAAQQQCNRRSFSDRLRVTPWPIAPDPQSREARQQRFAHFTELAIVSVQEIVDFAKQLPGFLQLSREDQIALLKTSAIEVMLLETSRRYNPGSESITFLKDFSYNREDFAKAGLQVEFINPIFEFSRAMNELQLNDAEFALLIAISIFSADRPNVQDQLQVERLQHTYVEALHAYVSINHPHDPLMFPRMLMKLVSLRTLSSVHSEQVFALRLQDKKLPPLLSEIWDVHE | ||||||
Domain | 207-445 | NR LBD | ||||
Sequence: EQLGMIEKLVAAQQQCNRRSFSDRLRVTPWPIAPDPQSREARQQRFAHFTELAIVSVQEIVDFAKQLPGFLQLSREDQIALLKTSAIEVMLLETSRRYNPGSESITFLKDFSYNREDFAKAGLQVEFINPIFEFSRAMNELQLNDAEFALLIAISIFSADRPNVQDQLQVERLQHTYVEALHAYVSINHPHDPLMFPRMLMKLVSLRTLSSVHSEQVFALRLQDKKLPPLLSEIWDVHE |
Sequence similarities
Belongs to the nuclear hormone receptor family. NR1 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length445
- Mass (Da)50,418
- Last updated2011-07-27 v3
- Checksum1A426DF38D935731
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A2AGR4 | A2AGR4_MOUSE | Nr1h3 | 385 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 399 | in Ref. 1; CAB51952/CAB51923 | ||||
Sequence: P → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ132599 EMBL· GenBank· DDBJ | CAB51952.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ132600 EMBL· GenBank· DDBJ | CAB51952.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ132601 EMBL· GenBank· DDBJ | CAB51923.1 EMBL· GenBank· DDBJ | mRNA | ||
AF085745 EMBL· GenBank· DDBJ | AAD16050.1 EMBL· GenBank· DDBJ | mRNA | ||
AL691450 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |