Nr1h4
entrez
60351
canonical
uniprot
Q62735
canonical
ensembl
ENSRNOG00000007197
resolver
ensp
ENSRNOP00000009910
resolver
ensp
ENSRNOP00000073765
resolver
enst
ENSRNOT00000009910
resolver
enst
ENSRNOT00000091227
resolver
genesymbol
Nr1h4
resolver
genesymbol_syn
Bar
resolver
genesymbol_syn
Fxr
resolver
genesymbol_syn
Rip14
resolver
uniprot
A0A0G2K6D2
resolver
uniprot
A0A8L2Q4E9
resolver
uniprot
Q5XI75
resolver
uniprot_entry
A0A0G2K6D2_RAT
resolver
uniprot_entry
A0A8L2Q4E9_RAT
resolver
uniprot_entry
NR1H4_RAT
resolver
uniprot_entry
Q5XI75_RAT
resolver
amino_acid_sequence
MNLIGPSHLQATDEFALSENLFGVLTEHAAGPLGQNLDLESYSPYNNVQFPQVQPQISSSSYYSNLGFYPQQPEDWYSPGLYELRRMPTESVYQGETEVSEMPVTKKPRMAASSAGRIKGDELCVVCGDRASGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCVMDMYMRRKCQDCRLRKCREMGMLAECLLTEIQCKSKRLRKNVKQHADQTVNEDSEGRDLRQVTSTTKLCREKTELTVDQQTLLDYIMDSYSKQRMPQEITNKILKEEFSAEENFLILTEMATSHVQILVEFTKRLPGFQTLDHEDQIALLKGSAVEAMFLRSAEIFNKKLPAGHADLLEERIRKSGISDEYITPMFSFYKSVGELKMTQEEYALLTAIVILSPDRQYIKDREAVEKLQEPLLDVLQKLCKIYQPENPQHFACLLGRLTELRTFNHHHAEMLMSWRVNDHKFTPLLCEIWDVQ
uniprot
proteins
function
FUNCTION: Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response. The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity. In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression. The function also involves the coordinated induction of hepatic KLB/beta-klotho expression. Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA. Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element. Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance. Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier. Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells. Mediates trans-repression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2. Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling. {ECO:0000250|UniProtKB:Q60641, ECO:0000250|UniProtKB:Q96RI1, ECO:0000269|PubMed:10744760, ECO:0000269|PubMed:20305288}.
uniprot
proteins
mass_dalton
53935
uniprot
proteins
post_translational_modification
PTM: Acetylated by EP300. Lys-210 as is the major acetylation site for EP300; the dynamically regulated acetylation inhibits heterodimerization with RXRA and transactivation activity. Deacetylated by SIRT1. {ECO:0000250|UniProtKB:Q96RI1}.; PTM: Methylation may increase transactivation of target genes. {ECO:0000250|UniProtKB:Q96RI1}.; PTM: Phosphorylation by PKC/PRKCA increases transactivation activity by promoting association with PPARGC1A. {ECO:0000250|UniProtKB:Q96RI1}.; PTM: Sumoylated upon ligand binding. {ECO:0000250|UniProtKB:Q96RI1}.
uniprot
proteins
protein_family
NR1 subfamily
uniprot
proteins
protein_family
Nuclear hormone receptor family
uniprot
proteins
pubmed
10744760
uniprot
proteins
pubmed
12718893
uniprot
proteins
pubmed
12917342
uniprot
proteins
pubmed
20305288
uniprot
proteins
pubmed
7774010
uniprot
proteins
sequence_length
469
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q60641, ECO:0000250|UniProtKB:Q96RI1, ECO:0000305}.
uniprot
proteins