NR1H4
entrez
9971
canonical
uniprot
Q96RI1
canonical
ensembl
ENSG00000012504
resolver
ensp
ENSP00000188403
resolver
ensp
ENSP00000376712
resolver
ensp
ENSP00000447149
resolver
ensp
ENSP00000448506
resolver
ensp
ENSP00000448978
resolver
ensp
ENSP00000496908
resolver
ensp
ENSP00000579457
resolver
ensp
ENSP00000678509
resolver
genesymbol
NR1H4
resolver
genesymbol_syn
BAR
resolver
genesymbol_syn
FXR
resolver
genesymbol_syn
HRR1
resolver
genesymbol_syn
RIP14
resolver
hgnc
HGNC:7967
resolver
uniprot
A1L4K5
resolver
uniprot
B6ZGS9
resolver
uniprot
B7Z412
resolver
uniprot
B7ZM06
resolver
uniprot
F1DAL1
resolver
uniprot
F8VYG8
resolver
uniprot
Q8NFP5
resolver
uniprot
Q8NFP6
resolver
uniprot
Q92943
resolver
uniprot_entry
B6ZGS9_HUMAN
resolver
uniprot_entry
F1DAL1_HUMAN
resolver
uniprot_entry
NR1H4_HUMAN
resolver
uniprot_sec
A1L4K5
resolver
uniprot_sec
B7Z412
resolver
uniprot_sec
B7ZM06
resolver
uniprot_sec
F8VYG8
resolver
uniprot_sec
Q8NFP5
resolver
uniprot_sec
Q8NFP6
resolver
uniprot_sec
Q92943
resolver
amino_acid_sequence
MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAKGVLTEQVAGPLGQNLEVEPYSQYSNVQFPQVQPQISSSSYYSNLGFYPQQPEEWYSPGIYELRRMPAETLYQGETEVAEMPVTKKPRMGASAGRIKGDELCVVCGDRASGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCVMDMYMRRKCQECRLRKCKEMGMLAECMYTGLLTEIQCKSKRLRKNVKQHADQTVNEDSEGRDLRQVTSTTKSCREKTELTPDQQTLLHFIMDSYNKQRMPQEITNKILKEEFSAEENFLILTEMATNHVQVLVEFTKKLPGFQTLDHEDQIALLKGSAVEAMFLRSAEIFNKKLPSGHSDLLEERIRNSGISDEYITPMFSFYKSIGELKMTQEEYALLTAIVILSPDRQYIKDREAVEKLQEPLLDVLQKLCKIHQPENPQHFACLLGRLTELRTFNHHHAEMLMSWRVNDHKFTPLLCEIWDVQ
uniprot
proteins
disease_involvement
DISEASE: Note=May be involved in intrahepatic cholestasis of pregnancy. {ECO:0000305|PubMed:17681172}.; DISEASE: Note=May be involved in cholesterol cholelithiasis. {ECO:0000305|PubMed:17931734}.; DISEASE: Cholestasis, progressive familial intrahepatic, 5 (PFIC5) [MIM:617049]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC5 is an autosomal recessive, severe form characterized by onset of intralobular cholestasis in the neonatal period. {ECO:0000269|PubMed:26888176}. Note=The disease is caused by variants affecting the gene represented in this entry.
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 (PubMed:10334992, PubMed:10334993, PubMed:21383957, PubMed:22820415). 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 (By similarity). 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) (By similarity). 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) (PubMed:12754200, PubMed:15471871, PubMed:17895379). 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) (PubMed:10514450, PubMed:15239098, PubMed:16269519). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression (PubMed:12815072, PubMed:19085950). The function also involves the coordinated induction of hepatic KLB/beta-klotho expression (By similarity). 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 (PubMed:12806625, PubMed:16946559). 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 (PubMed:12554753, PubMed:12660231, PubMed:15337761). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) (PubMed:11579204). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element (PubMed:11927623, PubMed:21804189). Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) (PubMed:12891557). 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) (By similarity). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance (PubMed:20447400). Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier (By similarity). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells (PubMed:21242261). 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 (PubMed:19864602). 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) (By similarity). {ECO:0000250|UniProtKB:Q60641, ECO:0000250|UniProtKB:Q62735, ECO:0000269|PubMed:10334992, ECO:0000269|PubMed:10334993, ECO:0000269|PubMed:10514450, ECO:0000269|PubMed:11579204, ECO:0000269|PubMed:11927623, ECO:0000269|PubMed:12554753, ECO:0000269|PubMed:12660231, ECO:0000269|PubMed:12718892, ECO:0000269|PubMed:12754200, ECO:0000269|PubMed:12806625, ECO:0000269|PubMed:12815072, ECO:0000269|PubMed:12891557, ECO:0000269|PubMed:14684751, ECO:0000269|PubMed:15239098, ECO:0000269|PubMed:15337761, ECO:0000269|PubMed:15471871, ECO:0000269|PubMed:16269519, ECO:0000269|PubMed:16946559, ECO:0000269|PubMed:17895379, ECO:0000269|PubMed:18621523, ECO:0000269|PubMed:19085950, ECO:0000269|PubMed:19410460, ECO:0000269|PubMed:19586769, ECO:0000269|PubMed:19864602, ECO:0000269|PubMed:20447400, ECO:0000269|PubMed:21242261, ECO:0000269|PubMed:21804189, ECO:0000269|PubMed:23928191, ECO:0000305|PubMed:21383957, ECO:0000305|PubMed:22820415}.; FUNCTION: [Isoform 1]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191}.; FUNCTION: [Isoform 2]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA), NR0B2/SHP (inducible by unconjugated CDCA DCA and ACA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191}.; FUNCTION: [Isoform 3]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191}.; FUNCTION: [Isoform 4]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, ACA and DCA), NR0B2/SHP (inducible by unconjugated CDCA, ACA and DCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; most efficient isoform compared to isoforms 1 to 3; not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191, ECO:0000269|PubMed:26888176}.
uniprot
proteins
mass_dalton
55914
uniprot
proteins
mutagenesis
MUTAGEN 132; /note="K->R: Abrogates SUMO1-mediated inhibition of ligand-induced transcactivation at ABCB11/BSEP and NR0B2/SHP promoters; when associated with R-289 and A-291."; /evidence="ECO:0000269|PubMed:23546875"; MUTAGEN 132; /note="K->R: Decreases transcriptional activation SLC51A/OSTA, SLC51B/OSTB and ABCB11/BSEP, no effect on interaction with RXRA and SETD7."; /evidence="ECO:0000269|PubMed:23462506"; MUTAGEN 145; /note="S->A: Impairs ligand-dependent transactivation activity, impairs interaction with PPARGC1A; when associated with A-164."; /evidence="ECO:0000269|PubMed:18755856"; MUTAGEN 164; /note="S->A: Impairs ligand-dependent transactivation activity, impairs interaction with PPARGC1A; when associated with A-145."; /evidence="ECO:0000269|PubMed:18755856"; MUTAGEN 167; /note="K->R: Decreases transcriptional activation of SLC51B/OSTB, no effect on SLC51A/OSTA and ABCB11/BSEP, no effect on interaction with RXRA and SETD7."; /evidence="ECO:0000269|PubMed:23462506"; MUTAGEN 220; /note="K->R: Decreases transcriptional activation of SLC51B/OSTB, no effect on SLC51A/OSTA and ABCB11/BSEP, impairs interaction with RXRA and SETD7."; /evidence="ECO:0000269|PubMed:23462506"; MUTAGEN 227; /note="K->R: Decreases transcriptional activation SC51A/OSTA, SLC51B/OSTB and ABCB11/BSEP, impairs interaction with RXRA and enhances interaction with SETD7, decreases association with ABCB11/BSEP promoter."; /evidence="ECO:0000269|PubMed:23462506"; MUTAGEN 289; /note="K->R: Abrogates SUMO1-mediated inhibition of ligand-induced transcactivation at ABCB11/BSEP and NR0B2/SHP promoters; when associated with R-132 and A-291."; /evidence="ECO:0000269|PubMed:23546875"; MUTAGEN 291; /note="E->A: Abrogates SUMO1-mediated inhibition of ligand-induced transcactivation at ABCB11/BSEP and NR0B2/SHP promoters; when associated with R-132 and R-289."; /evidence="ECO:0000269|PubMed:23546875"; MUTAGEN 353; /note="K->R: Decreases transcriptional activation SLC51A/OSTA, SLC51B/OSTB and ABCB11/BSEP, no effect on interaction with RXRA and SETD7, decreases association with ABCB11/BSEP promoter."; /evidence="ECO:0000269|PubMed:23462506"; MUTAGEN 455; /note="R->S: As a heterodimer with RXRA, impaired transcriptional activity."; /evidence="ECO:0000269|PubMed:30275017"; MUTAGEN 456; /note="T->A: Impairs transcriptional activation of ABCB11/BSEP."; /evidence="ECO:0000269|PubMed:18668687"; MUTAGEN 474; /note="K->R: Decreases transcriptional activation SLC51A/OSTA, SLC51B/OSTB and ABCB11/BSEP, no effect on interaction with RXRA and impairs interaction with SETD7."; /evidence="ECO:0000269|PubMed:23462506
uniprot
proteins
post_translational_modification
PTM: Acetylated by EP300. Lys-227 as is the major acetylation site for EP300; the dynamically regulated acetylation inhibits heterodimerization with RXRA and transactivation activity. Deacetylated by SIRT1. {ECO:0000269|PubMed:18755856}.; PTM: Methylation may increase transactivation of target genes. {ECO:0000269|PubMed:22345554}.; PTM: Phosphorylation by PKC/PRKCA increases transactivation activity by promoting association with PPARGC1A. {ECO:0000269|PubMed:18755856}.; PTM: Sumoylated upon ligand binding. {ECO:0000269|PubMed:19864602, ECO:0000269|PubMed:23546875}.
uniprot
proteins
protein_family
NR1 subfamily
uniprot
proteins
protein_family
Nuclear hormone receptor family
uniprot
proteins
pubmed
10334992
uniprot
proteins
pubmed
10334993
uniprot
proteins
pubmed
10514450
uniprot
proteins
pubmed
11579204
uniprot
proteins
pubmed
11927623
uniprot
proteins
pubmed
12016314
uniprot
proteins
pubmed
12062799
uniprot
proteins
pubmed
12554753
uniprot
proteins
pubmed
12660231
uniprot
proteins
pubmed
12718892
uniprot
proteins
pubmed
12718893
uniprot
proteins
pubmed
12754200
uniprot
proteins
pubmed
12806625
uniprot
proteins
pubmed
12815072
uniprot
proteins
pubmed
12891557
uniprot
proteins
pubmed
14684751
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15187081
uniprot
proteins
pubmed
15202934
uniprot
proteins
pubmed
15239098
uniprot
proteins
pubmed
15337761
uniprot
proteins
pubmed
15471871
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15911693
uniprot
proteins
pubmed
16269519
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
16946559
uniprot
proteins
pubmed
17681172
uniprot
proteins
pubmed
17895379
uniprot
proteins
pubmed
17931734
uniprot
proteins
pubmed
18391212
uniprot
proteins
pubmed
18621523
uniprot
proteins
pubmed
18668687
uniprot
proteins
pubmed
18755856
uniprot
proteins
pubmed
19085950
uniprot
proteins
pubmed
19159286
uniprot
proteins
pubmed
19393742
uniprot
proteins
pubmed
19410460
uniprot
proteins
pubmed
19556342
uniprot
proteins
pubmed
19586769
uniprot
proteins
pubmed
19805516
uniprot
proteins
pubmed
19833092
uniprot
proteins
pubmed
19864602
uniprot
proteins
pubmed
19883617
uniprot
proteins
pubmed
20095622
uniprot
proteins
pubmed
20447400
uniprot
proteins
pubmed
21242261
uniprot
proteins
pubmed
21383957
uniprot
proteins
pubmed
21804189
uniprot
proteins
pubmed
22345554
uniprot
proteins
pubmed
22820415
uniprot
proteins
pubmed
23235576
uniprot
proteins
pubmed
23462506
uniprot
proteins
pubmed
23546875
uniprot
proteins
pubmed
23928191
uniprot
proteins
pubmed
26888176
uniprot
proteins
pubmed
30275017
uniprot
proteins
sequence_length
486
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19864602}.; SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000269|PubMed:23928191}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:23928191}.; SUBCELLULAR LOCATION: [Isoform 3]: Nucleus {ECO:0000269|PubMed:23928191}.; SUBCELLULAR LOCATION: [Isoform 4]: Nucleus {ECO:0000269|PubMed:23928191}.
uniprot
proteins