Nr1h4
entrez
20186
canonical
uniprot
Q60641
canonical
ensembl
ENSMUSG00000047638
resolver
ensp
ENSMUSP00000053092
resolver
ensp
ENSMUSP00000100933
resolver
ensp
ENSMUSP00000100934
resolver
genesymbol
Nr1h4
resolver
genesymbol_syn
Bar
resolver
genesymbol_syn
Fxr
resolver
genesymbol_syn
Rip14
resolver
uniprot
D3YTT2
resolver
uniprot
E9QJW2
resolver
uniprot
Q3V1T8
resolver
uniprot
Q60642
resolver
uniprot
Q60643
resolver
uniprot_entry
NR1H4_MOUSE
resolver
uniprot_entry
Q3V1T8_MOUSE
resolver
uniprot_sec
D3YTT2
resolver
uniprot_sec
E9QJW2
resolver
uniprot_sec
Q60642
resolver
uniprot_sec
Q60643
resolver
amino_acid_sequence
MVMQFQGLENPIQISLHHSHRLSGFVPEGMSVKPAKGMLTEHAAGPLGQNLDLESYSPYNNVPFPQVQPQISSSSYYSNLGFYPQQPEDWYSPGIYELRRMPAETGYQGETEVSEMPVTKKPRMAAASAGRIKGDELCVVCGDRASGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCVMDMYMRRKCQECRLRKCKEMGMLAECMYTGLLTEIQCKSKRLRKNVKQHADQTANEDDSEGRDLRQVTSTTKFCREKTELTADQQTLLDYIMDSYNKQRMPQEITNKILKEEFSAEENFLILTEMATSHVQILVEFTKKLPGFQTLDHEDQIALLKGSAVEAMFLRSAEIFNKKLPAGHADLLEERIRKSGISDEYITPMFSFYKSVGELKMTQEEYALLTAIVILSPDRQYIKDREAVEKLQEPLLDVLQKLCKMYQPENPQHFACLLGRLTELRTFNHHHAEMLMSWRVNDHKFTPLLCEIWDVQ
uniprot
proteins
disease_involvement
DISEASE: Note=Activation protects mice against cholestasis, development of chronical intestinal inflammation and fibrosis. May suppress intestinal tumorigenesis. {ECO:0000269|PubMed:19047134, ECO:0000269|PubMed:19864602, ECO:0000269|PubMed:22057115}.
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 in innate immune response (PubMed:11030617, 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 (PubMed:20091679, PubMed:20483916). 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) (PubMed:21383957, PubMed:25545350, PubMed:25651182). 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:21383957). In ileal enterocytes activates FABP6/IBABP (involved in cytosolic transport), SLC51A/OSTA and SLC51B/OSTB (involved in secretion of conjugated BAs to the portal blood), and repressor NR0B2/SHP thereby indirectly inhibiting SLC10A2/ASBT (involved in BA uptake) (By similarity). In the intestine activates FGF15 expression and secretion leading to hepatic CYP7A1 repression; the function also involves the coordinated induction of hepatic KLB/beta-klotho expression (PubMed:16213224, PubMed:26505219). Transcriptional activation of FABP6/IBAP and SCD1 but not of ABCB11 is isoform-specific (PubMed:12393883). 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 (By similarity). Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 isoform SREBP-1C (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly) (PubMed:12421815, PubMed:15146238). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) (PubMed:11579204). Transrepresses APOA1 probably involving a monomeric competition with NR2A1 for binding to a DR1 element (PubMed:21804189). Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) (PubMed:12891557, PubMed:15146238). 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 (PubMed:15564327, PubMed:16410358, PubMed:16446356, PubMed:16557297, 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 (PubMed:16473946, PubMed:21242261). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells (PubMed:19864602). Mediates transrepression 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 (By similarity). Involved in the TLR9-mediated protective mechanism in intestinal inflammation (PubMed:23372731). Plays a anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling (PubMed:18972444). {ECO:0000250|UniProtKB:Q62735, ECO:0000250|UniProtKB:Q96RI1, ECO:0000269|PubMed:11030617, ECO:0000269|PubMed:11579204, ECO:0000269|PubMed:11706036, ECO:0000269|PubMed:12004058, ECO:0000269|PubMed:12393883, ECO:0000269|PubMed:12421815, ECO:0000269|PubMed:12660231, ECO:0000269|PubMed:12891557, ECO:0000269|PubMed:15146238, ECO:0000269|PubMed:15564327, ECO:0000269|PubMed:16213224, ECO:0000269|PubMed:16410358, ECO:0000269|PubMed:16446356, ECO:0000269|PubMed:16473946, ECO:0000269|PubMed:16557297, ECO:0000269|PubMed:16946559, ECO:0000269|PubMed:18972444, ECO:0000269|PubMed:19864602, ECO:0000269|PubMed:20091679, ECO:0000269|PubMed:20447400, ECO:0000269|PubMed:20483916, ECO:0000269|PubMed:21242261, ECO:0000269|PubMed:21804189, ECO:0000269|PubMed:23372731, ECO:0000269|PubMed:25545350, ECO:0000269|PubMed:25651182, ECO:0000269|PubMed:26505219, ECO:0000305|PubMed:21383957, ECO:0000305|PubMed:22820415}.; FUNCTION: [Isoform 2]: Activates transcription of IBAP and SDC1. {ECO:0000269|PubMed:12393883}.; FUNCTION: [Isoform 4]: Activates transcription of IBAP and SDC1. {ECO:0000269|PubMed:12393883}.
uniprot
proteins
mass_dalton
55994
uniprot
proteins
mutagenesis
MUTAGEN 370; /note="K->N: Increases affinity to CDCA and transcriptional activity in response to CDCA; when associated with I-388."; /evidence="ECO:0000269|PubMed:12004058"; MUTAGEN 388; /note="V->I: Increases affinity to CDCA and transcriptional activity in response to CDCA; when associated with N-370."; /evidence="ECO:0000269|PubMed:12004058
uniprot
proteins
post_translational_modification
PTM: Acetylated by EP300 (PubMed:18842595). Lys-228 as is the major acetylation site for EP300; the dynamically regulated acetylation inhibits heterodimerization with RXRA and transactivation activity. Deacetylated by SIRT1 (By similarity). Elevated acetylation levels are found in metabolic disease states (mouse models of obesity and type II diabetes) (PubMed:19883617). {ECO:0000250|UniProtKB:Q96RI1, ECO:0000269|PubMed:18842595, ECO:0000269|PubMed:19883617}.; 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
11030617
uniprot
proteins
pubmed
11579204
uniprot
proteins
pubmed
11706036
uniprot
proteins
pubmed
12004058
uniprot
proteins
pubmed
12393883
uniprot
proteins
pubmed
12421815
uniprot
proteins
pubmed
12660231
uniprot
proteins
pubmed
12891557
uniprot
proteins
pubmed
14729567
uniprot
proteins
pubmed
15146238
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15564327
uniprot
proteins
pubmed
16213224
uniprot
proteins
pubmed
16410358
uniprot
proteins
pubmed
16446356
uniprot
proteins
pubmed
16473946
uniprot
proteins
pubmed
16557297
uniprot
proteins
pubmed
16946559
uniprot
proteins
pubmed
18842595
uniprot
proteins
pubmed
18972444
uniprot
proteins
pubmed
19047134
uniprot
proteins
pubmed
19393742
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19805516
uniprot
proteins
pubmed
19864602
uniprot
proteins
pubmed
19883617
uniprot
proteins
pubmed
20091679
uniprot
proteins
pubmed
20447400
uniprot
proteins
pubmed
20483916
uniprot
proteins
pubmed
21242261
uniprot
proteins
pubmed
21383957
uniprot
proteins
pubmed
21804189
uniprot
proteins
pubmed
22057115
uniprot
proteins
pubmed
22820415
uniprot
proteins
pubmed
23372731
uniprot
proteins
pubmed
25545350
uniprot
proteins
pubmed
25651182
uniprot
proteins
pubmed
26505219
uniprot
proteins
pubmed
7760852
uniprot
proteins
sequence_length
488
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19864602}.
uniprot
proteins